Morbidity profile of inmates in old age homes in Mangalore, South India

2016-05-28T10-24-59Z
Source: International Journal of Medical Science and Public Health
Usha Rani S Padmanabha, Nalam Udayakiran, Puneeth Nagarajaiah, Vinayak J Kempaller.
Background: Ageing is a natural and inevitable process. As per WHO, in 2012, it has been estimated that over 8% of the total population is aged above 60 years. This proportion is expected to increase to 12% by 2025 and over 20% by 2050. India is witnessing a rapid increment in aged population constituting 8.2% of the national population. The old age homes, which were uncommon, have recently spread across the country indicating the growing rift between the generations. Objective: To assess the morbidity and sociodemographic profile of inmates in old age homes in Mangalore. Materials and Methods: The present study was a cross-sectional study done in three selected old age homes in Mangalore from June 2015 to August 2015. Universal sampling was done to obtain a sample size of 87. Totally, 80 inmates were enrolled. Data were obtained by interviewer method, medical records, and clinical examination, by using a pretested questionnaire after obtaining an informed consent. Results: Among the 80 inmates, 25% were male and 75% were female, out of which 63% were in the age group of 6070 years. Among the elders, 69% were widow/widower, 55% did not have any source of income, 29% were illiterate and 46% had completed primary education, 75% had musculoskeletal disorders, 69 % had visual defects, 64% were hypertensive, 30% had dental problems, and 28% were diabetic. Conclusion: There is an essential need for specialized geriatric clinics. Proper and regular health checkups should be conducted in old age homes with referral services. There is a need for insurance coverage for all the elders to meet their medical expenses.


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A study on musculoskeletal disorders distribution and health-seeking behavior among geriatric people in the field practice area of rural health and training center of a tertiary care hospital

2016-05-28T10-24-59Z
Source: International Journal of Medical Science and Public Health
Harshal Gajanan Mendhe, Narni Hanumanth, Gangi Harika.
Background: The World Health Organization (WHO) Technical Report 2003 stated that musculoskeletal disorders (MSDs) include osteoporosis, osteoarthritis, rheumatoid arthritis, spinal disorders, severe limb injury, trauma, or fracture. The burden of MSDs is global and looking at the gravity of the situation, WHO declared 20002010 as the bone and joint decade. As the geriatric people are more vulnerable to osteoporotic changes, there is a possibility that prevalence of MSDs will be more. So this cross-sectional study has been carried out among the geriatric people. Objective: To assess the sociodemographic profiles of geriatric people, to find out the prevalence of MSDs among study participants, and to assess their health-seeking behavior toward MSD. Materials and Methods: A total of 400 geriatric people were included in the study as study participants. Systematic sampling was followed to identify the household. The semi-structured questionnaire from the SJH Report was used to gather information regarding MSD problems. Result: A total of 43% of the study participants belonged to lower middle class family, 48% participants had joint pain, and 21% had backache. Knee joint was the most commonly affected joint. Backache was more common in women (67%) than in men (33%) and was found to be statistically significant. A total of 31% of the participants had osteoarthritis, 2% had rheumatoid arthritis, 7% had soft tissue rheumatism, 1% had monoarticular joint pain and gout, 4.75% had severe limb injury, trauma, and fracture, 26% had pain at any site, and 13.3% had no complaint at all. Overall prevalence of MSD was 61%. A total of 45% were seeking treatment from local RMP, whereas 28% did not seek any treatment for MSD problem. Conclusion: The geriatric people should undergo investigations such as serum calcium, vitamin D-3, and bone marrow density.


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Assessment of the quality of life indices in adolescents with Acne vulgaris

2016-05-28T10-24-59Z
Source: International Journal of Medical Science and Public Health
Tejaswi Cherukuri; Rangaraj Murugaiyan; Karthikeyan Kaliaperumal.
Background: Acne vulgaris, a multifactorial disease, is one of the most common dermatological conditions that is encountered in clinical practice and affecting approximately 80% adolescents and young adults at some stage. Objective: To study the quality of life in adolescents with acne and its relation with severity. Materials and Methods: A hospital-based cross-sectional study was carried out in the Dermatology Outpatient Department of a tertiary care hospital from January 2014 to December 2014. All the patients who fulfilled the inclusion criteria were chosen from the Dermatology Out-Patient Department during the specified period of time. Cardiff acne disability index (CADI) and separate Child dermatology life quality index (CDLQI) and adult Dermatology life quality index (DLQI) were assessed depending on the age of the patient. Data were entered and analyzed using Epi Info software (version 3.4.3). Categorical data were analyzed using the Pearsons χ2-test and significant P-value was fixed at P

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Obstructive sleep apnea among patients attending Family Medicine Centers, Military Hospital in Khamis Mushait city, Saudi Arabia

2016-05-28T10-24-59Z
Source: International Journal of Medical Science and Public Health
Mana Mubarak Alshahrani, Sultan Mohammed Alshahrani, Ibrahim Saeed Alarfaj, Shamsun Nahar.
Background: Obstructive sleep apnea (OSA) is a prevalent condition affecting at least 2% to 4% of the adult population. Patients are not routinely screened for symptoms of OSA as a part of their initial medical evaluation. Objective: To identify the prevalence and correlates of individuals who are at risk of OSA among adults attending to family medicine centers in Military Hospital in Khamis Mushait city, KSA. Materials and Methods: A cross-sectional study was carried out utilizing the Berlin questionnaire to identify patients who are at high risk for OSA among adult attendees of family medicine centers in Military Hospital in Khamis Mushait city, KSA. The study was conducted between October 1st and December 31st, 2015. An interview questionnaire including in addition to Belin questionnaire, demographic and personal data, smoking, and medical history was utilized. In addition, anthropometric measures including body weight, height, body mass index (BMI), neck circumference (NC), and waist/hip ratio for central obesity were measured. Result: The study included 413 patients. Their age ranged between 18 and 93 years with a mean of 39.6 ± 13.5 years. Slightly more than half of them (217; 52.5%) were females. Approximately half of the participants (201; 48.7%) were obese and 124 (30%) were overweight. Sixty-one subjects, representing 14.8% participants were at high risk of sleep apnea syndrome. Snoring was present in 37.3% subjects. Results of multivariate logistic regression analysis revealed that females were less likely to be at high risk of sleep apnea syndrome compared to males (AOR = 0.24 95% CI: 0.100.54, p = 0.001). Obese subjects were at higher risk of sleep apnea syndrome compared to normal subjects (AOR = 12.67 95% CI: 3.0053.55, p = 0.001). Current smokers were more likely to be at higher risk of sleep apnea syndrome compared to nonsmokers (AOR = 3.46 95% CI: 1.259.58, p = 0.017). Patients with history of chronic diseases were at higher risk of sleep apnea syndrome compared to those without history of chronic diseases (AOR = 2.96 95% CI: 1.505.81, p = 0.002). Conclusion: The study has shown that a considerable proportion of adults attending family medicine centers in Khamis Mushait, KSA are at higher risk for obstructive sleep apnea. Males, smokers, obese, and those with history of chronic diseases were at higher significant risk for OSA compared to their counterparts.


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High-resolution telomere fluorescence in situ hybridization reveals intriguing anomalies in germ cell tumors

Publication date: August 2016
Source:Human Pathology, Volume 54
Author(s): Mohammed Talha Shekhani, John R. Barber, Stephania M. Bezerra, Christopher M. Heaphy, Nilda Diana Gonzalez Roibon, Diana Taheri, Leonardo O. Reis, Gunes Guner, Corinne E. Joshu, George J. Netto, Alan K. Meeker
Testicular germ cell tumor (TGCT) is the most common malignancy of young men. Most patients are completely cured, which distinguishes these from most other malignancies. Orchiectomy specimens (n=76) were evaluated using high-resolution (single-cell discriminative) telomere-specific fluorescence in situ hybridization (FISH) with simultaneous Oct4 immunofluorescence to describe telomere length phenotype in TGCT neoplastic cells. For the first time, the TGCT precursor lesion, germ cell neoplasia in situ (GCNIS) is also evaluated in depth. The intensity of the signals from cancerous cells was compared to the same patient's reference cells—namely, healthy germ cells (defined as "medium" length) and interstitial/somatic cells (defined as "short" telomere length). We observed short telomeres in most GCNIS and pure seminomas (P=.006 and P=.0005, respectively). In contrast, nonseminomas displayed longer telomeres. Lesion-specific telomere lengths were documented in mixed tumor cases. Embryonal carcinoma (EC) demonstrated the longest telomeres. A fraction of EC displays the telomerase-independent alternative lengthening of telomeres (ALT) phenotype (24% of cases). Loss of ATRX or DAXX nuclear expression was strongly associated with ALT; however, nuclear expression of both proteins was retained in half of ALT-positive ECs. The particular distribution of telomere lengths among TGCT and GCNIS precursors implicate telomeres anomalies in pathogenesis. These results may advise management decisions as well.



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Dendritic cells in renal biopsies of patients with acute tubulointerstitial nephritis

Publication date: August 2016
Source:Human Pathology, Volume 54
Author(s): Mingyu Cheng, Xin Gu, Guillermo A. Herrera
Dendritic cells (DCs) play a critical role in the regulation of the adaptive immune response and can be separated into 2 major subsets: myeloid (mDC) and plasmacytoid (pDC) DCs. Acute tubulointerstitial nephritis (ATIN) is a common cause of injury to renal tubules and interstitium resulting from the interplay of tubular cells and inflammatory cells and their products. However, the involvement of DCs in ATIN is still unknown. In this study, the participation and localization of myeloid (CD1c) and plasmacytoid (CD303) DC subsets in the biopsies from patients with ATIN (n=20), lupus nephritis (n=17, positive control), or minimal change disease (n=14, negative control) were investigated. DCs were identified morphologically within the tubulointerstitium in the renal biopsies by transmission electron microscopy interacting with surrounding tubules and inflammatory cells. Direct immunofluorescence showed that both CD1c+DCs and CD303+ DCs exist in all the renal biopsies. As compared with minimal change disease, biopsies with ATIN had significantly increased CD1c+DCs (P<.001) and CD303+ DCs (P<.001). The number of CD1c+DCs in ATIN was significantly higher than that in lupus nephritis (P<.02), whereas the number of CD303+ DCs in ATIN was slightly but not significantly higher than that in lupus nephritis (P=.2). DCs in the biopsies with ATIN were restricted to the tubulointerstitium forming dense networks, and most of them maintained immature state. All these findings suggest that DC subsets may be differentially involved in the pathogenesis of ATIN. Their potential role in intrarenal regulation of immune responses in ATIN is proposed.



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Biventricular conversion for Fontan failure

Abstract

Certain cardiac malformations may pose difficulties in achieving a biventricular repair, and univentricular repair may be selected for them if the Fontan criteria are satisfied. However, univentricular palliation is not without its own drawbacks. We present a patient with double outlet of the right ventricle with pulmonic stenosis where the Fontan operation was conducted but where there was early Fontan failure in the short term and she needed conversion to a biventricular physiology.

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Photoplethysmography respiratory rate monitoring in patients receiving procedural sedation and analgesia for upper gastrointestinal endoscopy

Abstract

The value of capnography during procedural sedation and analgesia (PSA) for the detection of hypoxaemia during upper gastrointestinal (UGI) endoscopic procedures is limited. Photoplethysmography respiratory rate (RRp) monitoring may provide a useful alternative, but the level of agreement with capnography during PSA is unknown. We therefore investigated the level of agreement between the RRp and capnography-based RR (RRc) during PSA for UGI endoscopy. This study included patients undergoing PSA for UGI endoscopy procedures. Pulse oximetry (SpO₂) and RRc were recorded in combination with Nellcor 2.0 (RRp) monitoring (Covidien, USA). Bland–Altman analysis was used to evaluate the level of agreement between RRc and RRp. Episodes of apnoea, defined as no detection of exhaled CO₂ for minimal 36 s, and hypoxaemia, defined as an SpO₂ < 92 %, were registered. A total of 1054 min of data from 26 patients were analysed. Bland–Altman analysis between the RRc and RRp revealed a bias of 2.25 ± 5.41 breath rate per minute (brpm), with limits of agreement from −8.35 to 12.84 brpm for an RR ≥ 4 brpm. A total of 67 apnoea events were detected. In 21 % of all apnoea events, the patient became hypoxaemic. Hypoxaemia occurred 42 times with a median length of 34 (19–141) s, and was preceded in 34 % of the cases by apnoea and in 64 % by an RRc ≥ 8 brpm. In 81 % of all apnoea events, photoplethysmography registered an RRp ≥ 4 brpm. We found a low level of agreement between capnography and the plethysmography respiratory rate during procedural sedation for UGI endoscopy. Moreover, respiratory rate derived from both the capnogram and photoplethysmogram showed a limited ability to provide warning signs for a hypoxaemic event during the sedation procedure.

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Reliability of metatarsophalangeal and ankle joint torque measurements by an innovative device

Publication date: Available online 27 May 2016
Source:Gait & Posture
Author(s): Hok-Sum Man, Aaron Kam-Lun Leung, Jason Tak-Man Cheung, Thorsten Sterzing
The toe flexor muscles maintain body balance during standing and provide push-off force during walking, running, and jumping. Additionally, they are important contributing structures to maintain normal foot function. Thus, weakness of these muscles may cause poor balance, inefficient locomotion and foot deformities. The quantification of metatarsophalangeal joint (MPJ) stiffness is valuable as it is considered as a confounding factor in toe flexor muscles function.MPJ and ankle joint stiffness measurement is still largely depended on manual skills as current devices do not have good control on alignment, angular joint speed and displacement during measurement.Therefore, this study introduces an innovative dynamometer and protocol procedures for MPJ and ankle Joint torque measurement with precise and reliable foot alignment, angular joint speed and displacement control. Within-day and between-day test-retest experiments on MPJ and ankle joint torque measurement were conducted on ten and nine healthy male subjects respectively. The mean peak torques of MPJ and ankle joint of between-day and within-day measurement were 1.50±0.38Nm/deg and 1.19±0.34Nm/deg. The corresponding torques of the ankle joint were 8.24±2.20Nm/deg and 7.90±3.18Nm/deg respectively. Intraclass-correlation coefficients (ICC) of averaged peak torque of both joints of between-day and within-day test-retest experiments were ranging from 0.91 to 0.96, indicating the innovative device is systematic and reliable for the measurements and can be used for multiple scientific and clinical purposes.



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The estrogenic properties of Danggui Buxue Tang, a Chinese herbal decoction, are triggered predominantly by calycosin in MCF-7 cells

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Amy G.W. Gong, Kei M. Lau, Miranda L. Xu, Huang Q. Lin, Tina T.X. Dong, Ken Y.Z. Zheng, K.J. Zhao, Karl W.K. Tsim
BackgroundDanggui Buxue Tang (DBT), a Chinese herbal decoction containing Astragali Radix (AR; roots of Astragalus memebranaceus (Fisch.) Bunge var. mongholicus (Bunge) Hsiao) and Angelicae Sinensis Radix (ASR; roots of Angelica sinensis Oliv.) at a weight ratio of 5:1, is used to improve menopausal syndromes in women. Several lines of evidence indicate that DBT has strong estrogenic property; however, the action mechanism of this herbal decoction is not known. Calycosin, a major flavonoid in AR, shares similar structure with β-estradiol, and thus which is hypothesized to be the key compound of DBT in responsible for such estrogenic properties.AimsWe aimed to determine the role of calycosin in DBT in terms of its estrogenic functions by the creation of calycosin-depleted DBT (DBTΔcal) and calycosin-added DBT (DBT+cal) herbal extracts.MethodsThe signalings triggered by DBT∆cal, DBT+cal, and parental DBT were compared in cultured MCF-7 cells by determining: (i) the activation of estrogen responsive element; (ii) the phosphorylation of estrogen receptor α (ERα); and (iii) the phosphorylation of Erk1/2. The DBT-induced responses were in dose- and/or time-dependent manners.ResultsThe estrogenic signals triggered by DBT were markedly reduced in DBTΔcal, and in contrast the addition of calycosin in DBT, i.e. DBT+cal, enhanced the responses by 2–5 folds; however, calycosin alone did not show such properties. In parallel, the DBT-induced responses could be significantly blocked by inhibitors for estrogen receptor and mitogen activated protein kinases.ConclusionThus, we hypothesize that calycosin is an indispensable chemical in DBT, and which plays a linker in orchestrating multi-components of DBT as to achieve the maximal estrogenic functions. These discoveries should be invaluable in drug development and in investigating the modernization of traditional Chinese medicine from a new perspective.

Graphical abstract

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Genotoxicity and cytotoxicity of oxindole alkaloids from Uncaria tomentosa (cat's claw): Chemotype relevance

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Samuel Kaiser, Ânderson Ramos Carvalho, Vanessa Pittol, Fabrícia Dietrich, Fabiana Manica, Michel Mansur Machado, Luis Flávio Souza de Oliveira, Ana Maria Oliveira Battastini, George González Ortega
Ethnopharmacological relevanceUncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) or cat's claw is a climber vine from the South American rainforest used in folk medicine for cancer treatment. Its antitumor activity has been mostly ascribed to pentacyclic oxindole alkaloids (POA) from stem bark and leaves while the activity of tetracyclic oxindole alkaloids (TOA) remains unknown. In recent times, the occurrence of three chemotypes based on its oxindole alkaloid profile was noticed in U. tomentosa, namely, chemotype I (POA cis D/E ring junction); chemotype II (POA trans D/E ring junction) or chemotype III (TOA). Consequently, the relationship between the chemotype and cytotoxic and genotoxic activities deserves attention.Aim of the studyTo evaluate the influence of cat's claw chemotypes on genotoxicity and cytotoxicity against non malignant and malignant human cell line models.Material and methodsFour authentic stem bark cat's claw samples (SI-SIV) and two leaf samples (LII and LIII) were analyzed by HPLC-PDA, properly extracted and fractioned by ion-exchange to obtain oxindole alkaloid purified fractions (OAPFs). The freeze-dried fractions were assayed for genotoxicity and cytotoxicity against human leukocytes (non malignant cell line) by the micronuclei frequency method and the alkaline comet DNA assay, and the trypan blue method, respectively. Moreover, the cytotoxicity of each OAPF was evaluated against a human bladder cancer cell line (T24) and human glioblastoma cell line (U-251-MG) by MTT method (malignant cell lines). Additionally, the isomerization of oxindole alkaloids throughout the course of cell incubation was monitored by HPLC-PDA.ResultsBased on HPLC-PDA analyses, sample SI was characterized as chemotype I, while samples SII and LII were characterized as chemotype II, and samples SIII, SIV and LIII as chemotype III. The chemotypes showed comparable cytotoxic activity toward malignant cell lines (T24 and U-251-MG) unlike human leukocytes (non malignant cell line), where this activity was clearly distinct. Chemotype II (POA trans D/E ring junction) showed a higher selectivity index (SI) against malignant cells (SI=1.11–3.04) than chemotype I (SI=0.10−0.19) and III (SI=0.21–0.57). No important genotoxic potential was found by micronuclei frequency and alkaline comet DNA assays. Despite the isomerization of oxindole alkaloids during the cell incubation, the chemotype of the cat's claw samples remained unchanged.ConclusionCat's claw chemotypes showed different selectivity against human malignant cells, so that the correct identification of each chemotype seems to be important to better understand its antitumor potential.

Graphical abstract

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Antihypertensive activity of 80% methanol seed extract of Calpurnia aurea (Ait.) Benth. subsp. aurea (Fabaceae) is mediated through calcium antagonism induced vasodilation

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Yohannes Getiye, Tesfaye Tolessa, Ephrem Engidawork
Ethnopharmacological relevanceCalpurnia aurea (Ait.) Benth. subsp. aurea (CASA) (Fabaceae) seeds are used to treat hypertension in Ethiopian folklore medicine, particularly by Shinasha, Agew-awi and Amhara people in northwest Ethiopia. However, the claim has so far not been substantiated scientifically.Aim of the studyThe study was conducted to evaluate the antihypertensive activity of 80% methanol extract of CASA in animal model of hypertension as well as its vasorelaxant effect and possible underlying mechanisms in isolated guinea pig aorta.Material and methodsHypotensive and antihypertensive effect of CASA extract was determined in vivo through the intravenous (iv) route in normotensive and hypertensive anesthetized rats using 2-kidney-1-clip (2K1C) rat model. Ex vivo, guinea pig thoracic aortic rings were isolated and suspended in organ bath, and the vasodepressor effects as well as the mechanism of action of the extract were studied by means of isometric tension recording experiments.ResultsThe blood pressure fell dose-dependently and significantly in renal hypertensive and normotensive rats following i.v. administration, suggesting that the hydroalcoholic extract possesses hypotensive and antihypertensive effects. The extract also caused a dose-dependent relaxation of aorta pre-contracted with KCl at a concentration of 5–250mg/L, with a maximum relaxation of 92.1% achieved at 250mg/L. The relaxation mechanism was found to be independent of the muscarinic receptors, histamine receptors, ATP dependent K⁺ channels, cyclooxygenase enzymes, cGMP/NO pathway and the endothelium system. The extract caused rightward shift of the Ca⁺⁺ dose–response curves, similar to that caused by verapamil, indicating that it produced vasorelaxation by inhibiting extracellular Ca²⁺ influx.ConclusionsThe findings demonstrate that the plant is endowed with antihypertensive effect, providing evidence for its traditional use. The effect may be, at least in part, due to dilation of blood vessels through blockage of Ca²⁺ channels.

Graphical abstract

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The effects of Arnebia euchroma ointment on second-degree burn wounds: a randomized clinical trial

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Ebrahim Nasiri, Seyed Jalal Hosseinimehr, Ahmad Zaghi Hosseinzadeh, Mohammad Azadbakht, Jafar Akbari, Masoud Azadbakht
Ethnobotanical relevanceBurn injuries can cause detrimental long-term consequences and call for immediate management. Avicenna's Canon of Medicine, describing the use of Abu-Khalsa (Arnebia euchroma) (AE) as being effective for burn healing. The purpose of this study was to evaluate the healing effects of AE ointment (AEO) on patients with a second-degree burn wound and compare its results with silver sulfadiazine cream (SSD).Materials and methodsIn this prospective, single-blind clinical trial, 45 patients with similar types of second-degree burns at two different sites of the body were randomly assigned to the two treatment groups. One burn wound site of the patient was treated with SSD and another similar burn wound site with AEO once a day until complete healing was achieved. Wound size and percentage of wound healing were evaluated at 15 days. Satisfaction, clinical adverse events such as pain, burning, warming, erythema, edema, infection, inflammation, and general wound area were assessed on a visual analogue scales, and 6-point scales.ResultsThe healing time was significantly shorter in the site treated with AEO than SSD (13.9±5.3 vs. 17.5±6.9 days, respectively). The severity of pain and burning were reduced in the AEO site compared with SSD site at the time of dressing change, while the warming score was significantly higher in the AEO wound area. Side-effects were lower in the site treated with AEO.ConclusionIn this clinical study, we demonstrated that AEO has benefits over SSD in the treatment of second-degree burn wounds and wound healing and is a viable medication for the management of second-degree burns.

Graphical abstract

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Lonicerae Japonicae Flos attenuates diabetic retinopathy by inhibiting retinal angiogenesis

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Lingyu Zhou, Tianyu Zhang, Bin Lu, Zengyang Yu, Xiyu Mei, Palida Abulizi, Lili Ji
Ethnopharmacological relevanceLonicerae Japonicae Flos (Jin-Yin-Hua) is a well-known traditional Chinese medicine used for clearing away heat and toxic material.Aim of the studyThis study aims to observe the attenuation of aqueous extract of Lonicerae Japonicae Flos (FL) against streptozotocin (STZ)-induced diabetic retinopathy (DR) and its engaged mechanism.Materials and methodsSTZ-induced proliferative DR (PDR) for 5 month in C57BL/6 mice was used in this study. Retinal vessels were observed by immunofluorescence staining with cluster of differentiation 31 (CD31) and histopathological evaluation. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum vascular endothelial growth factor (VEGF) content. Cell proliferation was detected by 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay in choroid-retinal endothelial RF/6A cells. VEGF-induced tube formation in RF/6A cells was observed. The contents of chlorogenic acid (CGA), caffeic acid (CA), and luteolin in FL were detected by high-performance liquid chromatography (HPLC).ResultsHistopathological evaluation demonstrated that retinal vessels were increased in STZ-induced PDR mice, whereas FL decreased such increase. The results of CD31 staining also showed that FL decreased the increased number of retinal vessels in STZ-induced PDR mice. In addition, FL reduced the increased serum VEGF content in STZ-induced PDR mice. FL reduced VEGF-induced RF/6A cell proliferation in the concentration-dependent manner, but had no obvious effect on RF/6A cell viability without VEGF stimulation. VEGF-induced tube formation in RF/6A cells was inhibited by different concentrations of FL. CGA, CA and luteolin all inhibited VEGF-induced tube formation in RF/6A cells, and the lowest effective concentration of CGA and CA was both 0.625μM, but of luteolin was 5μM. Furthermore, the results of HPLC demonstrated that the amount of CGA was the highest in FL.ConclusionsFL ameliorates STZ-induced PDR by inhibiting retinal angiogenesis. Phenolic acid CGA is the main compound contributing to the inhibition of FL on retinal angiogenesis.

Graphical abstract

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Coptis chinensis Franch. extract up-regulate type I helper T-cell cytokine through MAPK activation in MOLT-4 T cell

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Eunhee Kim, Sejin Ahn, Hae-ik Rhee, Deug-chan Lee
Ethnopharmacological relevanceThe dried rhizome of Coptis chinensis Franch. (Huanglian) has been widely used in Asian traditional medicine. It was already known that Coptis chinensis Franch. rhizome has various pharmacological properties including its anti-oxidant, anti-cancer, and anti-inflammatory activity.Aim of the studyTo evaluate the immune-enhancement effect of the Coptis chinensis Franch. rhizome extract on helper T cells and its signaling mechanism.Materials and methodsMOLT-4 human T cell line was used to investigate the effect of the Coptis chinensis Franch. rhizome extract. Cell viability was measured by the MTT assay and cytokine expression level was analyzed by ELISA and qRTPCR. MAPKs signal molecule's activation level was detected by immunoblotting.ResultsThe expression of IFN-γ, a cytokine of type I helper T (Th1) cell, increased; however, IL-4 was not affected by the Coptis chinensis Franch. rhizome extract. Other Th1 cytokines, such as IL-1β, IL-2, and IL-6, also increased. These data suggest that the Coptis chinensis Franch. rhizome extract activates MOLT-4 cell to Th1 cell, not type II helper T cell. Furthermore, the Coptis chinensis Franch. rhizome extract activates the Mitogen-activated protein kinase (MAPKs) signaling pathways.ConclusionThe results obtained from this study suggest that the Coptis chinensis Franch. rhizome extract should be used as an immune enhancer in anti-inflammatory medicine, adjuvant materials, and as a supplement to treat weakened immune system.

Graphical abstract

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Effects of Viola yedoensis Makino anti-itching compound on degranulation and cytokine generation in RBL-2H3 mast cells

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Hai-Rong Zeng, Bing Wang, Zhen Zhao, Qi Zhang, Mei-Yun Liang, Ya-Qi Yao, Ka Bian, Wei-Rong Zhang
Ethnopharmacological relevanceThe Chinese herb compound prescription Viola yedoensis Makino Anti-itching Compound (VYAC), which consists of Viola yedoensis Makino, herb, Sophora flavescens Aiton, root, and Dictamnus dasycarpus Turcz, root and rhizome, has been traditionally used to treat various skin allergic inflammatory diseases in clinic.Aim of the studyThe aim of this study is to investigate the effects of VYAC on degranulation and to determine its anti-inflammatory mechanism in RBL-2H3 mast cells.Materials and methodsVYAC was extracted with water-coction extraction (Shufen et al., 2012). The aqueous extracts were concentrated in vacuum under reduced pressure and lyophilized using a freeze dryer, and lyophilized powder was obtained. MTT was used to evaluate the cytotoxic of VYAC on RBL-2H3 cells. Degranulation was carried out with RBL-2H3 cell model, which was stimulated with A23187 plus PMA. β-Hexosaminidase and histamine were measured to evaluate degranulation. The mRNA levels of inflammation cytokines (IL-1β, TNF-α, IL-6, and iNOS) were investigated by RT-PCR to explain the anti-inflammatory mechanism of VYAC.ResultsVYAC did not show cytotoxic effect on RBL-2H3 cells in the range of 25–400μg/mL. A higher dose of VYAC (800μg/mL) showed significant cytotoxicity (P<0.05). VYAC could significantly inhibit β-hexosaminidase and histamine release when treated with 100, 200, and 400μg/mL (P<0.05), but could not significantly inhibit β-Hexosaminidase and histamine release when treated with 25 and 50μg/mL (p>0.05). The mRNA levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, and iNOS) could significantly decrease when treated with 200 and 400μg/mL (P<0.05) of VYAC, which were associated with the development of inflammation.ConclusionsResults showed that VYAC inhibited β-hexosaminidase and histamine release, which was inhibit A23187 plus PMA stimulated RBL-2H3 cell degranulation and downregulated inflammatory cytokines (IL-1β, TNF-α, IL-6, and iNOS) expression to block inflammatory development.

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Piper nigrum ethanolic extract rich in piperamides causes ROS overproduction, oxidative damage in DNA leading to cell cycle arrest and apoptosis in cancer cells

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Valdelúcia Maria Alves de Souza Grinevicius, Maicon Roberto Kviecinski, Nádia Sandrini Ramos Santos Mota, Fabiana Ourique, Luiza Sheyla Evenni Porfirio Will Castro, Rafaela Rafognato Andreguetti, João Francisco Gomes Correia, Danilo Wilhem Filho, Claus Tröger Pich, Rozangela Curi Pedrosa
Ethnopharmacological relevanceAyurvedic and Chinese traditional medicine and tribal people use herbal preparations containing Piper nigrum fruits for the treatment of many health disorders like inflammation, fever, asthma and cancer. In Brazil, traditional maroon culture associates the spice Piper nigrum to health recovery and inflammation attenuation.Aims of the studyThe aim of the current work was to evaluate the relationship between reactive oxygen species (ROS) overproduction, DNA fragmentation, cell cycle arrest and apoptosis induced by Piper nigrum ethanolic extract and its antitumor activity.MethodsThe plant was macerated in ethanol. Extract constitution was assessed by TLC, UV–vis and ESI-IT-MS/MS spectrometry. The cytotoxicity, proliferation and intracellular ROS generation was evaluated in MCF-7 cells. DNA damage effects were evaluated through intercalation into CT-DNA, plasmid DNA cleavage and oxidative damage in CT-DNA. Tumor growth inhibition, survival time increase, apoptosis, cell cycle arrest and oxidative stress were assessed in Ehrlich ascites carcinoma-bearing mice.ResultsExtraction yielded 64mg/g (36% piperine and 4.2% piperyline). Treatments caused DNA damage and reduced cell viability (EC50=27.1±2.0 and 80.5±6.6µg/ml in MCF-7 and HT-29 cells, respectively), inhibiting cell proliferation by 57% and increased ROS generation in MCF-7 cells (65%). Ehrlich carcinoma was inhibited by the extract, which caused reduction of tumor growth (60%), elevated survival time (76%), cell cycle arrest and induced apoptosis. The treatment with extract increased Bax and p53 and inhibited Bcl-xL and cyclin A expression. It also induced an oxidative stress in vivo verified as enhanced lipid peroxidation and carbonyl proteins content and increased activities of glutathione reductase, superoxide dismutase and catalase. GSH concentration was decreased in tumor tissue from mice.ConclusionThe ethanolic extract has cytotoxic and antiproliferative effect on MCF-7 cells and antitumor effect in vivo probably due to ROS overproduction that induced oxidative stress affecting key proteins involved in cell cycle arrest at G1/S and triggering apoptosis. Finally, the overall data from this study are well in line with the traditional claims for the antitumor effect of Piper nigrum fruits.

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Huangqi decoction alleviates dimethylnitrosamine-induced liver fibrosis: An analysis of bile acids metabolic mechanism

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Ya-Nan Song, Gui-Biao Zhang, Yi-Yu Lu, Qi-Long Chen, Li Yang, Zheng-Tao. Wang, Ping Liu, Shi-Bing Su
Ethnopharmacological relevanceHuangqi Decoction (HQD), a classical traditional Chinese medicine (TCM) formula, is used to treating liver injury in China. The aim of the study is to investigate mechanisms of HQD against dimethylnitrosamine (DMN)-induced liver fibrosis underlying metabolic profiles of bile acids.Materials and methodsDMN-induced liver fibrosis rats were administrated HQD and its compounds, astragalosides (AS), glycyrrhizic acid (GA) and their combination. The anti-fibrosis effects were evaluated and targeted metabolomics by UPLC-MS was used to examine whether HQD had an influence on bile acid metabolism. The levels of mRNAs associated with bile acid metabolism were expressed by RT-PCR. Chenodeoxycholic acid (CDCA)-induced hepatic stellate cells (HSCs) proliferation and activation were examined using MTS assay and Western blot.ResultsHistopathological changes and serum liver function in HQD group had significant improvements (P<0.01). Concentrations of free bile acids and taurine conjugates were significantly increased in DMN group (P<0.05). HQD and its compounds restored the increased bile acids to normal levels, and HQD was more effected on parts of bile acids. Furthermore, the levels of mRNAs related bile acid synthesis and reabsorption such as CYP7A1, CYP8B1, CYP27A1, OATP2, OATP3, OATP4 and NTCP were significantly down-regulated in DMN group (P<0.05), mRNAs related excretion such as MRP3 and BESP were up-regulated (P<0.01), and CYP7A1, CYP8B1, OATP3, OATP4, NTCP and MRP3 restored to normal levels by HQD treatment. Moreover, CDCA-induced HSCs proliferation and activation were weaken by HQD (P<0.05) with down-regulated α-SMA, TGF-β1, p-Smad2 and p-Smad3 expressions.ConclusionsHQD alleviated DMN-induced liver fibrosis with a better effect than its compounds, which may be involved in the regulation of bile acid metabolism enzyme. Moreover, HQD may inhibit CDCA-induced HSCs proliferation and activation.

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Mechanisms underlying the cardioprotective effect of Salvianic acid A against isoproterenol-induced myocardial ischemia injury in rats: Possible involvement of L-type calcium channels and myocardial contractility

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Qiongtao Song, Xi Chu, Xuan Zhang, Yifan Bao, Yuanyuan Zhang, Hui Guo, Yang Liu, Hongying Liu, Jianping Zhang, Ying Zhang, Li Chu
Ethnopharmacological relevanceSalvianic acid A (SAA), which is the main water-soluble fraction in Radix Salviae Milthiorrhizae, has been widely applied for treating cardiovascular diseases in China.Aim of the studyTo explore the effects of SAA against myocardial ischemia injury induced by isoproterenol (ISO) in rats and to clarify its underlying myocardial protective mechanisms based on l-type calcium channels and myocardial contractility.Materials and methodsThe myocardial ischemia injured rat model was induced by administering ISO (85mg/kg) subcutaneously at evenly spaced intervals throughout the day and night for 2 consecutive days. Serum cardiac biomarkers were analyzed, and heart tissues were isolated and prepared for histopathology assay. The regulatory effects of SAA on the L-type calcium current (ICa-L) in rat ventricular myocytes were observed by the patch clamp technique. The IonOptix Myocam detection system was used to observe the contractility of isolated rat ventricular myocytes.ResultsSAA significantly ameliorated changes in heart morphology and electrocardiographic patterns and reduced serum levels of creatine kinase and lactate dehydrogenase in the ISO-induced myocardial ischemia injured rat model. Meanwhile, SAA reduced ICa-L in a concentration-time dependent way with an IC50 of 1.47×10⁻⁵M, upshifted the current-voltage, activation, and inactivation curves of ICa-L, and significantly inhibited the amplitude of the cell shortening.ConclusionsThese results indicate that SAA exhibits significant cardioprotective effects against the ISO-induced myocardial ischemia injury, potentially through inhibiting ICa-L and decreasing myocardial contractility.

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New halogenated constituents from Mangifera zeylanica Hook.f. and their potential anti-cancer effects in breast and ovarian cancer cells

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Meran Keshawa Ediriweera, Kamani Hemamala Tennekoon, Achyut Adhikari, Sameera Ranganath Samarakoon, Ira Thabrew, E. Dilip de Silva
Ethnopharmacological relevenceMangifera zeylanica Hook.f. (Anacardiaceae) is a plant endemic to Sri Lanka. Its bark has been used in traditional and Ayurvedic medicine for the treatment of various diseases including some cancers.Aim of the studyThis study was planned to isolate and identify potentially cytotoxic compounds from the bark of M. zeylanica, which may have contributed to its ethno pharmacological use in the treatment of cancer.Materials and methodsThe chloroform extract of M. zeylanica bark which is cytotoxic to breast and ovarian cancer cells was fractionated using column chromatography and preparative reversed phase high performance liquid chromatography to isolate four compounds. Structures of the isolated compounds were elucidated by means of ¹H- and ¹³C NMR spectroscopy, and mass spectrometric techniques. Cytotoxic potential of the isolated compounds was tested in MDA-MB-231 (triple negative breast cancer), MCF-7 (estrogen receptor positive breast cancer), SKOV-3 (ovarian epithelial cancer) and MCF-10A (normal mammary epithelial) cells by SRB assay. Human cancer drug target real-time PCR array was carried out to analyze regulation of possible cancer drug target genes in compound 2 treated triple negative breast cancer cells. DPPH radical scavenging and caspase 3 and 7 induction in response to isolated compounds were also studied.ResultsTwo new halogenated compounds, bromomangiferic acid (1), and chloromangiferamide (2) along with two known compounds quercetin (3), and catechin (4), were isolated from the bark of Mangifera zeylanica for the first time. Interestingly, chloromangiferamide showed cytotoxicity only to triple negative breast cancer cells [IC50:73.19±0.87µM (24h), 56.29±0.86µM (48h)] with no cytotoxicity to other two cancer cell lines or to normal mammary epithelial cells. Quercetin and catechin were cytotoxic to all three cancer cell lines while bromomangiferic acid had no effect. Chloromangiferamide significantly regulated expression of genes associated with apoptosis, drug metabolism, cell cycle, receptor tyrosine kinase signaling, protein kinases, histone deacetylases, growth factors and receptors, topoisomerases, PI-3 kinases and phosphatases in triple negative breast cancer cells.ConclusionSelective cytotoxic activity in triple negative breast cancer cells and regulation of some cancer drug target genes by chloromangiferamide indicate that it can be used to develop a potential chemotherapeutic agent for triple negative breast cancer cells.

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Poncirin and its metabolite ponciretin attenuate colitis in mice by inhibiting LPS binding on TLR4 of macrophages and correcting Th17/Treg imbalance

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Geum-Dan Kang, Dong-Hyun Kim
Ethnopharmacological relevanceThe fruit of Poncirus trifoliate, which contains poncirin as a main constituent, is frequently used in the traditional Chinese medicine for inflammation, asthma, and infection diseases.Aim of the studyTo examine anti-colitic effects of poncirin and ponciretin, a metabolite of poncirin by gut microbiota.Materials and methodsColitis was induced in mice by the intrarectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Inflammatory markers were analyzed by enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, confocal microscopy, and flow cytometry. Peritoneal macrophages were isolated from mice stimulated with 4% thioglycolate.ResultsPoncirin was metabolized to ponciretin in vitro and in vivo by gut microbiota of mice. Orally administered poncirin and ponciretin suppressed TNBS-induced colitis in mice: these inhibited colon shortening, myeloperoxidase activity, NF-κB activation, and Th17 cell differentiation, but increased occludin, claudin-1, and ZO-1 expressions and Treg cell differentiation. Poncirin and ponciretin suppressed the differentiation of splenocytes into Th17 cells and expression of IL-17 and Foxp3 in vitro, as well as the activation of macrophages stimulated with lipopolysaccharide (LPS) by inhibiting the binding of LPS on TLR4 of macrophages. These increased the differentiation of splenocytes into Treg cells. The ant-inflammatory effect of ponciretin was superior to that of poncirin.ConclusionOrally administered poncirin is metabolized to ponciretin by gut microbiota and poncirin and ponciretin attenuates colitis by suppressing NF-κB activation through the inhibition of LPS binding on macrophages and correcting Th17/Treg cell imbalance.

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Ethnobotanical uses of neem (Azadirachta indica A.Juss.; Meliaceae) leaves in Bali (Indonesia) and the Indian subcontinent in relation with historical background and phytochemical properties

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Wawan Sujarwo, Ary P. Keim, Giulia Caneva, Chiara Toniolo, Marcello Nicoletti
Ethnopharmacological relevanceNeem (Azadirachta indica; Meliaceae) is widely known for its cold pressed seed oil, mainly used as insecticide, but also for cosmetic, medicinal and agricultural uses. The seed oil is widely employed in the Indian subcontinent, and the leaves seem to have a lower relevance, but the ethnobotanical information of Bali (Indonesia) considers the utilisation of leaves for medicinal properties.Aim of the studyWe report ethnopharmacological information about current uses of neem, in particular of the leaves, besides the insecticidal one, we discuss on the historical background of their uses.Materials and methodsEthnobotanical data were collected using both literature and scientific references and semi-structured interviews with 50 informants (ages ranged between 14 and 76 years old) through the snowball method in thirteen aga (indigenous Balinese) villages, following Ethic code procedures. The informants were asked to specify: which part of the plant was used, and how that plant part was used. Plant specimens were collected, identified and made into herbarium voucher. In consideration of the high variability and complex chemical constituent of neem, a HPTLC analysis of neem leaves coming from both the Indonesian island of Bali and the Indian subcontinent was carried out.ResultsThe data on the medical use of traditional preparations from leaves of neem display a wide spectrum of applications. In the Indian subcontinent, neem leaves are used to treat dental and gastrointestinal disorders, malaria fevers, skin diseases, and as insects repellent, while the Balinese used neem leaves as a diuretic and for diabetes, headache, heartburn, and stimulating the appetite. Differences in utilisation cannot be related to chemical differences and other constituents besides limonoids must be investigated and related to the multipurpose activity of neem.ConclusionThis study revealed that neem leaves are believed to treat diabetes in both Balinese and Indian communities. Limonoids can not be considered the only responsible of digestive properties. Further research would be the validation of this report by enzymatic tests and the identification of active constituents.

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CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFF-activated CD4+ T cells

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Xiaoyi Jia, Fang Wei, Xiaojing Sun, Yan Chang, Shu Xu, Xuezhi Yang, Chun Wang, Wei Wei
Ethnopharmacological relevanceTotal glucosides of paeony (TGP) is the first anti-inflammatory immune regulatory drug approved for the treatment of rheumatoid arthritis in China. A novel compound, paeoniflorin-6′-O-benzene sulfonate (code CP-25), comes from the structural modification of paeoniflorin (Pae), which is the effective active ingredient of TGP. The aim of the present study is to investigate the effect of CP-25 on adjuvant arthritis (AA) fibroblast-like synoviocytes (FLS) co-cultured with BAFF-activated CD4⁺ T cells and the expression of BAFF-R in CD4⁺ T cells.MethodsThe mRNA expression of BAFF and its receptors was assessed by qPCR. The expression of BAFF receptors in CD4⁺ T cells was analyzed by flow cytometry. The effect of CP-25 on AA rats was evaluated by their joint histopathology. The cell culture growth of thymocytes and FLS was detected by cell counting kit (CCK-8). The concentrations of IL-1β, TNF-α, and IL-6 were measured by Enzyme-linked immunosorbent assay (ELISA).ResultsThe mRNA expression levels of BAFF and BAFF-R were enhanced in the mesenteric lymph nodes of AA rats, TACI expression was reduced, and BCMA had no change. The expression of BAFF-R in CD4⁺ T cells was also enhanced. CP-25 alleviated the joint histopathology and decreased the expression of BAFF-R in CD4⁺ T cells from AA rats in vivo. In vitro, CP-25 inhibited the abnormal cell culture growth of BAFF-stimulated thymocytes and FLS. In the co-culture system, IL-1β, IL-6 and TNF-α production was enhanced by FLS co-cultured with BAFF-activated CD4⁺ T cells. Moreover, BAFF-stimulated CD4⁺ T cells promoted the cell culture growth of FLS. The addition of CP-25 decreased the expression of BAFF-R in CD4⁺ T cells and inhibited the cell culture growth and cytokine secretion ability of FLS co-cultured with BAFF-activated CD4⁺ T cells.ConclusionThe present study indicates that CP-25 may repress the cell culture growth and cytokine secretion ability of FLS, and its inhibitory effects might be associated with its ability to inhibit the expression of BAFF-R in CD4⁺ T cells in a co-culture. These observations might provide a scientific basis for the development of new drugs for the treatment of autoimmune diseases by CP-25.

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Cis- and Trans-gnetin H from Paeonia suffruticosa suppress inhibitor kappa B kinase phosphorylation in LPS-stimulated human THP-1 cells

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Hyo S. Park, Eric J. Vick, Ying Gao, Chunnian He, Nadin Marwan Almosnid, Mary Farone, Anthony L. Farone
Ethnopharmacological relevanceThe inflammatory response is an important mechanism in host defense; however, overstimulation and chronic inflammation are involved in many important human diseases. Currently, tumor necrosis factor-alpha blockers such as infliximab and adalimumab along with methotrexate are used in cases of severe and chronic disease. However, there are severe side effects and limitations associated with these treatments. Cis- and trans-gnetin H are compounds isolated from the seeds of Paeonia suffruticosa, a medicinal plant used in traditional Chinese medicine for the treatment of many conditions, including inflammatory diseases. In this study, we investigated possible anti-inflammatory mechanisms of cis- and trans-gnetin H against LPS-stimulated human THP-1 cells.Material and methodsPMA-differentiated THP-1 cells were pretreated with increasing concentrations of cis- and trans-gnetin H with or without LPS. Following treatment, cytotoxicity and the TNF-α, IL-1β, and IL-8 response were measured. We also characterized the nuclear translocation of NF-κB subunit p65 (RelA) by immunofluorescence and then investigated NF-κB activation by measuring the phosphorylation of NF-κB mediators, IKK-β, IκB α, and p65 by western blotting.ResultsWe found that cis- and trans-gnetin H significantly inhibited the cytokine response in a concentration-dependent manner without affecting cell viability. Cis- and trans-gnetin H effectively inhibited nuclear translocation of p65 and phosphorylation of IKK-β, IκB α, and p65. While both compounds showed promising anti-inflammatory effects, trans-gnetin H was determined to be more effective in suppressing cytokine responses.ConclusionWe demonstrated that cis- and trans-gnetin H suppress cytokine response in LPS-stimulated THP-1 cells by preventing activation of key signaling molecules, IKK-β, IκB α, and p65, involved in the NF-κB pathway and suggest the use of cis- and trans-gnetin H in potential therapies for conditions and diseases associated with chronic inflammation.

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Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Na Liu, Hua Li Yang, Pu Wang, Yu Cheng Lu, Ying Juan Yang, Lan Wang, Shao Chin Lee
Ethnopharmacological relevanceAnnona muricata L. is used to treat cancer in some countries. Extracts of Annona muricata have been shown to cause apoptosis of various cancer cells in vitro, and inhibit tumor growth in vivo in animal models. However, the molecular mechanisms underlying its anti-cancer and apoptotic effects of the herb remain to be explored.Aim of studyThe study investigated the molecular mechanisms underlying liver cancer cell apoptosis triggered by the ethanol extract of leaves of Annona muricata L.Materials and methodsLiver cancer HepG2 cells were used as experimental model. MTT assay was employed to evaluate cell viability. Flow cytometry and TUNEL assays were performed to confirm apoptosis. We employed functional proteomic analysis to delineate molecular pathways underlying apoptosis triggered by the herbal extract.ResultsWe showed that the extract was able to reduce viability and trigger apoptosis of the cancer cells. Proteomic analysis identified 14 proteins associated with the extract-elicited apoptosis, which included the increased expression levels of HSP70, GRP94 and DPI-related protein 5. Western blot analysis confirmed that the extract did up-regulated the protein levels of HSP70 and GRP94. Results from bioinformatic annotation pulled out two molecular pathways for the extract, which, notably, included endoplasmic reticulum (ER) stress which was evidenced by the up-regulation of HSP70, GRP94 and PDI-related protein 5. Further examinations of typical protein signaling events in ER stress using western blot analysis have shown that the extract up-regulated the phorsphorelation of PERK and eIF2α as well as the expression level of Bip and CHOP.ConclusionOur results indicate that the ethanol extract of leaves of Annona muricata L. causes apoptosis of liver cancer cells through ER stress pathway, which supports the ethnomedicinal use of this herb as an alternative or complementary therapy for cancer.

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Knowledge and demand for medicinal plants used in the treatment and management of diabetes in Nyeri County, Kenya

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Loice N. Kamau, Mathiu P. Mbaabu, James M. Mbaria, Gathumbi P. Karuri, Stephen G. Kiama
Ethnopharmacological relevanceNon communicable diseases are currently a major health challenge facing humanity. Nyeri County has one of the highest diabetes prevalence in Kenya (12.6%), compared to the country's prevalence of 5.6%. The purpose of the study was to document; diabetes knowledge, medicinal plants and demand for the services of traditional medicine practitioners, in the management and treatment of diabetes.MethodsA cross-sectional study was carried out in the six constituencies in Nyeri, using pre-tested semi-structured questionnaires. Thirty practicing traditional medicine practitioners were purposively selected for the study. Field observation and identification was carried out on all plants that were cited during the interview. Plant samples were collected and voucher specimen deposited in the University of Nairobi Herbarium in the – School of Biological Sciences.ResultsThe study revealed 30 plant species in 28 genera and 23 families that are used by the traditional medicine practitioners to treat and manage diabetes. Demand for traditional medicine practitioners' services in the treatment of diabetes is low and often occurs when conventional drugs fail.ConclusionInteraction with the TMPs unveiled significant diversity of potential anti diabetic medicinal plants and in-depth ethnobotanical knowledge that they possessed. Preference for traditional herbal medicine was low despite wide ethnobotanical knowledge in the face of high prevalence of diabetes in the locality. The findings form the basis of pharmacological studies for standardization of the documented ethnomedicine used in the treatment and management of diabetes in the study area.

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Xiaotan Sanjie decoction inhibits angiogenesis in gastric cancer through Interleukin-8−linked regulation of the vascular endothelial growth factor pathway

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Jun Shi, Ye Lu, Pinkang Wei
Ethnopharmacological relevanceInterleukin-8 (IL-8) as a pro-angiogenic factor is strongly associated with gastric cancer metastasis. Xiaotan Sanjie (XTSJ) decoction is an empirical compound prescription based on the phlegm theory of traditional Chinese medicine. Previous studies have shown that XTSJ decoction decreases IL-8 level and formation of vasculogenic mimicry of gastric cancer.Aim of the studyTo investigate the link between Xiaotan Sanjie (XTSJ) decoction and IL-8 regulation in the angiogenesis of gastric cancer.Materials and methodsHuman umbilical vein endothelial cells (HUVECs) were co-cultured with SGC-7901 human gastric cancer cells and exposed to serum samples containing XTSJ decoction and/or IL-8 (1.0ng/mL). The canalization and migration capacities were evaluated by tube formation and transwell migration assay. Protein (immunofluorescence and Western blot) and mRNA (qPCR) expressions were measured in 24-h–cultured HUVECs for vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor receptor (VEGFR)-1, and VEGFR-2.ResultsIL-8 significantly promoted and XTSJ decoction inhibited HUVEC tube formation and migration. Links between IL-8 regulation and XTSJ decoction were found in tube formation and migration assays. IL-8 upregulated and XTSJ decoction downregulated VEGF-A, VEGFR-1, and VEGFR-2 protein levels. XTSJ decoction inhibited IL-8-induced VEGF-A and VEGFR-1 protein expressions. Similarly, IL-8 promoted VEGF-A, VEGFR-1, and VEGFR-2 mRNA levels; however, XTSJ decoction inhibited only VEGF-A mRNA. Interestingly, XTSJ decoction inhibited IL-8−induced VEGFR-1 and VEGFR-2 mRNA expression.ConclusionXTSJ decoction might inhibit angiogenesis in gastric cancer through IL-8-linked regulation of the VEGF pathway.

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Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator–activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Jing Ge, Jun-Jun Miao, Xin-Yi Sun, Jiang-Yi Yu
Ethnopharmacological relevanceAbelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of chronic kidney disease (CKD) in China. Huangkui capsule (HKC), an extract from AM, has been proved clinically effective in improving renal inflammation and glomerular injury in CKD. However, the mechanisms of HKC are still not fully understood.Aim of the studyPeroxisome proliferator–activated receptor (PPAR)-α/γ dual agonists have the potential to be used as therapeutic agents for the treatment of type 2 diabetes and diabetic nephropathy (DN). This study evaluated the function of Huangkui capsule (HKC), an extract from Abelmoschus manihot (L.) medic (AM), as a dual agonist for PPARα/γ and investigated its anti-DN effects in a DN rat model.Materials and methodsChIP and reporter gene assays were performed and the expression of PPARα/γ target genes was monitored to examine the ability of HKC to activate PPARα/γ. DN was induced in male Sprague–Dawley rats via unilateral nephrectomy and intraperitoneal injection of streptozotocin. HKC was administered to the diabetic nephropathy rats at three different doses: high dose HKC (300mg/kg/d); middle dose HKC (175mg/kg/d); and low dose HKC (75mg/kg/d). Irbesartan (4mg/kg/d body weight) was used as a positive control. Following 12 weeks' treatment, we measured general status, renal morphological appearance, proteinuria, blood biochemical parameters, and glomerular morphological changes. The expression of collagen IV, TGFβ, TNFα and IL-6 in renal tissue was evaluated. Endoplasmic reticulum (ER) stress in renal tissue was also analyzed.ResultsHKC enhanced the transcriptional activity of PPARα and PPARγ in cultured cells, livers and kidneys of DN rats, and it reduced serum triglyceride and cholesterol levels and fat in livers of DN rats. Furthermore, HKC reduced the expressions of inflammatory genes in kidneys of DN rats. Strikingly, HKC reduced ER stress and c-Jun NH2-terminal kinase activation in the liver and kidney of DN rats and subsequently improved renal injury.ConclusionsOur results show that HKC improved lipid metabolic disorders by activating PPARα/γ and attenuating ER stress. HKC could dose-dependently ameliorate renal inflammation and glomerular injury in DN rats. These results suggest that HKC has potential as an anti-DN agent for the treatment of DN in humans.

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Mitochondrial cAMP signaling

Abstract

Cyclic adenosine 3, 5′-monophosphate (cAMP) is a ubiquitous second messenger regulating many biological processes, such as cell migration, differentiation, proliferation and apoptosis. cAMP signaling functions not only on the plasma membrane, but also in the nucleus and in organelles such as mitochondria. Mitochondrial cAMP signaling is an indispensable part of the cytoplasm-mitochondrion crosstalk that maintains mitochondrial homeostasis, regulates mitochondrial dynamics, and modulates cellular stress responses and other signaling pathways. Recently, the compartmentalization of mitochondrial cAMP signaling has attracted great attentions. This new input should be carefully taken into account when we interpret the findings of mitochondrial cAMP signaling. In this review, we summarize previous and recent progress in our understanding of mitochondrial cAMP signaling, including the components of the signaling cascade, and the function and regulation of this signaling pathway in different mitochondrial compartments.

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Evaluation of NADPH oxidases as drug targets in a mouse model of familial amyotrophic lateral sclerosis

Publication date: August 2016
Source:Free Radical Biology and Medicine, Volume 97
Author(s): Tamara Seredenina, Zeynab Nayernia, Silvia Sorce, Ghassan J. Maghzal, Aleksandra Filippova, Shuo-Chien Ling, Olivier Basset, Olivier Plastre, Youssef Daali, Elisabeth J. Rushing, Maria T. Giordana, Don W. Cleveland, Adriano Aguzzi, Roland Stocker, Karl-Heinz Krause, Vincent Jaquet
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by progressive loss of motor neurons, gliosis, neuroinflammation and oxidative stress. The aim of this study was to evaluate the involvement of NADPH oxidases (NOX) in the oxidative damage and progression of ALS neuropathology. We examined the pattern of NOX expression in spinal cords of patients and mouse models of ALS and analyzed the impact of genetic deletion of the NOX1 and 2 isoforms as well as pharmacological NOX inhibition in the SOD1^G93A ALS mouse model.A substantial (10–60 times) increase of NOX2 expression was detected in three etiologically different ALS mouse models while up-regulation of some other NOX isoforms was model-specific. In human spinal cord samples, high NOX2 expression was detected in microglia. In contrast to previous publications, survival of SOD1^G93A mice was not modified upon breeding with constitutive NOX1 and NOX2 deficient mice. As genetic deficiency of a single NOX isoform is not necessarily predictive of a pharmacological intervention, we treated SOD1^G93A mice with broad-spectrum NOX inhibitors perphenazine and thioridazine. Both compounds reached in vivo CNS concentrations compatible with NOX inhibition and thioridazine significantly decreased superoxide levels in the spinal cord of SOD1^G93A mice in vivo. Yet, neither perphenazine nor thioridazine prolonged survival. Thioridazine, but not perphenazine, dampened the increase of microglia markers in SOD1^G93A mice. Thioridazine induced an immediate and temporary enhancement of motor performance (rotarod) but its precise mode of action needs further investigation. Additional studies using specific NOX inhibitors will provide further evidence on the relevance of NOX as drug targets for ALS and other neurodegenerative disorders.



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Release of bioactive peptides from polyurethane films in vitro and in vivo: Effect of polymer composition

Publication date: Available online 28 May 2016
Source:Acta Biomaterialia
Author(s): Jing Zhang, Trent M. Woodruff, Richard J. Clark, Darren J. Martin, Rodney F. Minchin
Thermoplastic polyurethanes (TPUs) are widely used in biomedical applications due to their excellent biocompatibility. Their role as matrices for the delivery of small molecule therapeutics has been widely reported. However, very little is known about the release of bioactive peptides from this class of polymers. Here, we report the release of linear and cyclic peptides from TPUs with different hard and soft segments. Solvent casting of the TPU at room temperature mixed with the different peptides resulted in reproducible efflux profiles with no evidence of drug degradation. Peptide release was dependent on the size as well as the composition of the TPU. Tecoflex 80A (T80A) showed more extensive release than ElastEon 5-325, which correlated with a degree of hydration. It was also shown that the composition of the medium influenced the rate and extent of peptide efflux. Blending the different TPUs allowed for better control of peptide efflux, especially the initial burst effect. Peptide-loaded TPU prolonged the plasma levels of the anti-inflammatory cyclic peptide PMX53, which normally has a plasma half-life of less than 30 min. Using a blend of T80A and E5-325, therapeutic plasma levels of PMX53 were observed up to 9 days following a single intraperitoneal implantation of the drug-loaded film. PMX53 released from the blended TPUs significantly inhibited B16-F10 melanoma tumor growth in mice demonstrating its bioactivity in vivo. This study provides important findings for TPU-based therapeutic peptide delivery that could improve the pharmacological utility of peptides as therapeutics.Statement of SignificanceTherapeutic peptides can be highly specific and potent pharmacological agents, but are poorly absorbed and rapidly degraded in the body. This can be overcome by using a matrix that protects the peptide in vivo and promotes its slow release so that a therapeutic effect can be achieved over days or weeks. Thermoplastic polyurethanes are a versatile family of polymers that are biocompatible and used for medical implants. Here, the release of several peptides from a range of polyurethanes was shown to depend on the type of polymer used in the polyurethane. This is the first study to examine polyurethane blends for peptide delivery and shows that the rate and extent of peptide release can be fine-tuned using different hard and soft segment mixtures in the polymer.

Graphical abstract

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Enhanced Cell Survival of pH-Sensitive Bioenergetic Nucleotide Nanoparticles in Energy/Oxygen-Depleted Cells and Their Intranasal Delivery for Reduced Brain Infarction

Publication date: Available online 28 May 2016
Source:Acta Biomaterialia
Author(s): Yeon Su Choi, Dong Youl Cho, Hye-Kyung Lee, Jung-Kyo Cho, Don Haeng Lee, You Han Bae, Ja-Kyeong Lee, Han Chang Kang
Nucleotides (NTs) (e.g., adenosine triphosphate) are very important molecules in the body. They generate bioenergy through phosphate group release, are involved in various biological processes and are used to treat various diseases that involve energy depletion. However, their highly anionic characteristics might limit delivery of exogenous NTs into the cell, which is required to realize their functions as bioenergy sources. In this study, ionic complexation between Ca²⁺ and NT phosphates was used to form Ca²⁺/NT nanocomplexes (NCs), and branched polyethyleneimine (bPEI1.8kDa) was coated on the surface of Ca²⁺/NT NCs via a simple electrostatic coating. The resultant Ca²⁺/NT/bPEI1.8kDa NCs were approximately 10-25 nm in size and had positive zeta-potentials, and their NT loading efficiency and content were approximately 60-75% and 10-20 wt%, respectively. Faster NT release from Ca²⁺/NT/bPEI1.8kDa NCs was induced by lower pH and by NTs with fewer phosphates. Reductions in cell viability in response to low temperature, serum deprivation, or hypoxia were recovered by NT delivery in Ca²⁺/NT/bPEI1.8kDa NCs. In a middle cerebral artery occlusion (MCAO)-induced post-ischemic rat model, the BBB (blood brain barrier)-detoured intranasal administration of Ca²⁺/ATP/bPEI1.8kDa NCs induced a better reduction in infarct volume and neurological deficits than did free ATP. In conclusion, intracellular NT delivery using Ca²⁺/NT/bPEI1.8kDa NCs might potentially enhance cell survival and reduce infarction in energy-/oxygen-depleted environments.Statement of significanceThis study describes bioenergetic nucleotide delivery systems and their preparation, physicochemical characterization, and biological characterization both in vitro and in vivo. Nucleotides, such as adenosine triphosphate (ATP) and guanosine triphosphate (GTP), are very important signaling and energy molecules in the body. However, research on these nucleotides using nanosized carriers has been very limited. Liposomal ATP delivery has been reported in heart and renal ischemia studies. Notably, although this delivery system has potential in energy-depleted environments (e.g., low temperature, serum deprivation, and hypoxia) and in brain ischemia, studies are lacking regarding these systems. Thus, we designed polycation-shielded Ca2+/nucleotide nanocomplexes using simple mixing, which produced 10- to 25-nm-sized particles. The nanocomplexes released nucleotides in response to acidic pH, and they enhanced cell survival rates under conditions of low temperature, serum deprivation, or hypoxia. Importantly, the nanocomplexes reduced cerebral infarct volumes in a post-ischemic rat model. Thus, our study demonstrates that a novel nucleotide nanocomplex could have potential for preventing or treating diseases that involve energy depletion, such as cardiac, cerebral, and retinal ischemia, and liver failure.

Graphical abstract

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Heparinized Collagen Sutures for Sustained Delivery of PDGF-BB: Delivery Profile and Effects on Tendon-derived Cells In-Vitro

Publication date: Available online 27 May 2016
Source:Acta Biomaterialia
Author(s): Mousa Younesi, Baris Ozgur Donmez, Anowarul Islam, Ozan Akkus
Suturing is the standard of repair for lacerated flexor tendons. Past studies focused on delivering growth factors to the repair site by incorporating growth factors to nylon sutures which are commonly used in the repair procedure. However, conjugation of growth factors to nylon or other synthetic sutures is not straightforward. Collagen holds promise as a suture material by way of providing chemical sites for conjugation of growth factors. On the other hand, collagen also needs to be reconstituted as a mechanically robust thread that can be sutured. In this study, we reconstituted collagen solutions as suturable collagen threads by using linear electrochemical compaction. Prolonged release of PDGF-BB (Platelet derived growth factor-BB) was achieved by covalent bonding of heparin to the collagen sutures. Tensile mechanical tests of collagen sutures before and after chemical modification indicated that the strength of sutures following chemical conjugation stages was not compromised. Strength of lacerated tendons sutured with epitendinous collagen sutures (11.2 ± 0.7 N) converged to that of the standard nylon suture (14.9 ± 2.9 N). Heparin conjugation of collagen sutures didn't affect viability and proliferation of tendon-derived cells and prolonged the PDGF-BB release up to 15 days. Proliferation of cells seeded on PDGF-BB incorporated collagen sutures was about 50% greater than those seeded on plain collagen sutures. Collagen that is released to the media by the cells increased by 120% under the effects of PDGF-BB and collagen production by cells was detectable by histology as of day 21. Addition of PDGF-BB to collagen sutures resulted in a moderate decline in the expression of the tendon-associated markers scleraxis, collagen I, tenomodulin, and COMP; however, expression levels were still greater than the cells seeded on collagen gel. The data indicate that the effects of PDGF-BB on tendon-derived cells mainly occur through increased cell proliferation and that longer term studies are needed to confirm whether this proliferation is outweighs the moderate reduction in the expression of tendon-associated genes.Statement of significanceA mechanically robust pure collagen suture was fabricated via linear electrocompaction and conjugated with heparin for prolonged delivery of PDFG-BB. Sustained delivery of the PDGF-BB improved the proliferation of tendon derived cells substantially at the expense of a moderate downregulation of tenogenic markers. The collagen threads were functionally applicable as epitendinous sutures when applied to chicken flexor tendons in vitro. Overall, electrocompacted collagen sutures holds potential to improve repair outcome in flexor tendon surgeries by improving cellularity and collagen production through delivery of the PDGF-BB. The bioinductive suture concept can be applied to deliver other growth factors for a wide-array of applications.

Graphical abstract

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Manual Tactile Test Predicts Sensorimotor Control Capability of Hands for Patients With Peripheral Nerve Injury

Publication date: June 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 6
Author(s): Hsiu-Yun Hsu, Shyh-Jou Shieh, Ta-Shen Kuan, Hsiu-Ching Yang, Fong-Chin Su, Haw-Yen Chiu, Li-Chieh Kuo
ObjectivesTo comprehend the merits of a Manual Tactile Test (MTT) in assessing hand sensorimotor functions by exploring the relations among 3 subtests along with the precision pinch performances for patients with peripheral nerve injuries (PNIs); and to understand the accuracy of the MTT by constructing the sensitivity and specificity of the test for patients with PNI.DesignCase-control study.SettingHospital and local community.ParticipantsPatients with PNI (n=28) were recruited along with age-, sex-, and handedness-matched healthy controls (n=28) (N=56).InterventionsNot applicable.Main Outcome MeasuresThe Semmes-Weinstein monofilament, moving and static 2-point discrimination, roughness differentiation, stereognosis and barognosis subtests of the MTT, and precision pinch performance were used to examine the sensory and sensorimotor status of the hand.ResultsThe worst results in all sensibility tests were found for the patients with PNI (P<.001) in comparison with the controls. Multiple linear regression analysis showed the MTT was a better indicator for predicting the sensorimotor capacity of hands in the patients with PNI (r²=.189, P=.003) than the traditional test (r²=.088, P=.051). The results of the receiver operating characteristic curve estimation show that the area under the curve was .968 and .959 for the roughness differentiation and stereognosis subtests, respectively, and .853 for the barognosis subtest, therefore revealing the accuracy of the MTT in assessing sensorimotor status for patients with PNI.ConclusionsThis study indicates that the MTT is highly accurate and a significant predictor of sensorimotor performance in hands of patients with PNI. The MTT could therefore help clinicians obtain a better understanding of the sensorimotor and functional status of the hand with nerve injuries.



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Evaluation of cystic duct patency: comparison of functional MR cholangiography with gadoxetate disodium and hepatobiliary scintigraphy in suspected acute cholecystitis

Publication date: September–October 2016
Source:Clinical Imaging, Volume 40, Issue 5
Author(s): Michael T. Corwin, Stephen Malutich, Edgardo S. Salcedo, Ghaneh Fananapazir, John M. Brock, John P. McGahan
PurposeThis study aims to compare assessment of cystic duct patency between gadoxetate disodium MRI and hepatobiliary scintigraphy.Materials and methodsWe performed a prospective study of patients who underwent gadoxetate disodium MRI within 16 h of scintigraphy.ResultsThe gallbladder filled on MRI and scintigraphy in 8 patients, none with acute cholecystitis. The mean time to gallbladder filling was 14.6 and 18.9 min for MRI and scintigraphy, respectively. The gallbladder did not fill on both MRI and scintigraphy in 3 patients, all of whom had acute cholecystitis.ConclusionEvaluation of cystic duct patency using gadoxetate disodium MRI is comparable to hepatobiliary scintigraphy.



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Effect of low-level laser therapy after rapid maxillary expansion: a clinical investigation

Abstract

To evaluate the effectiveness low-level laser therapy (LLLT) on the repair of the mid palatal suture, after rapid maxillary expansion (RME). A single-operator, randomized single-blind placebo-controlled study was performed at the Orthodontic Department at the Dental Hospital of Bellvitge. Barcelona University, Hospitalet de Llobregat, Spain. Thirty-nine children (range 6–12 years old), completed RME and were randomized to receive active LLLT (n = 20) or placebo (n = 19). The laser parameters and dose were 660 nm, 100 mW, CW, InGaAlP laser, illuminated area 0.26 cm², 332 mW/cm², 60 s to four points along midpalatal suture, and 30 s to a point each side of the suture. A total of seven applications were made on days 1, 7, 14, 28, 42, 56, and 70 of the retention phase RME. A cone beam computed tomography (CBCT) scan was carried out on the day of the first laser treatment, and at day 75, a second CBCT scan was performed. Two radiologists synchronized the slices of two scans to be assessed. P = 0.05 was considered to be statistically significant. At day 75 of the suture, the irradiated patients presented a greater percentage of approximate zones in the anterior (p = 0.008) and posterior (p = 0.001) superior suture—and less approximation in the posterior superior suture (p = 0.040)—than the placebo group. LLLT appears to stimulate the repair process during retention phase after RME.

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Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort

Abstract

Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome towards NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene P-values derived from differential expression values from GEO2R. Our study identified NPC association in the Gene Ontology (GO) axonemal dynein complex pathway (P_GWAS-GSEA=1.98x10⁻²; P_Expr-GSEA=1.27x10⁻²⁴; P_{Bonf-Combined}=4.15x10⁻²¹). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (P_{AmpliSeq-GSEA}=6.56x10⁻⁴). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort. This article is protected by copyright. All rights reserved.

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Changes in future air quality, deposition, and aerosol-cloud interactions under future climate and emission scenarios

Publication date: August 2016
Source:Atmospheric Environment, Volume 139
Author(s): Timothy Glotfelty, Yang Zhang, Prakash Karamchandani, David G. Streets
The prospect of global climate change will have wide scale impacts, such as ecological stress and human health hazards. One aspect of concern is future changes in air quality that will result from changes in both meteorological forcing and air pollutant emissions. In this study, the GU-WRF/Chem model is employed to simulate the impact of changing climate and emissions following the IPCC AR4 SRES A1B scenario. An average of 4 future years (2020, 2030, 2040, and 2050) is compared against an average of 2 current years (2001 and 2010). Under this scenario, by the Mid-21st century global air quality is projected to degrade with a global average increase of 2.5 ppb in the maximum 8-hr O3 level and of 0.3 μg m⁻³ in 24-hr average PM2.5. However, PM2.5 changes are more regional due to regional variations in primary aerosol emissions and emissions of gaseous precursor for secondary PM2.5. Increasing NOx emissions in this scenario combines with a wetter climate elevating levels of OH, HO2, H2O2, and the nitrate radical and increasing the atmosphere's near surface oxidation state. This differs from findings under the RCP scenarios that experience declines in OH from reduced NOx emissions, stratospheric recovery of O3, and increases in CH4 and VOCs. Increasing NOx and O3 levels enhances the nitrogen and O3 deposition, indicating potentially enhanced crop damage and ecosystem stress under this scenario. The enhanced global aerosol level results in enhancements in aerosol optical depth, cloud droplet number concentration, and cloud optical thickness. This leads to dimming at the Earth's surface with a global average reduction in shortwave radiation of 1.2 W m⁻². This enhanced dimming leads to a more moderate warming trend and different trends in radiation than those found in NCAR's CCSM simulation, which does not include the advanced chemistry and aerosol treatment of GU-WRF/Chem and cannot simulate the impacts of changing climate and emissions with the same level of detailed treatments. This study indicates that effective climate mitigation and emission control strategies are needed to prevent future health impact and ecosystem stress. Further, studies that are used to develop these strategies should use fully coupled models with sophisticated chemical and aerosol-interaction treatments that can provide a more realistic representation of the atmosphere.



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A study of the treatment of cutaneous fungal infection in animal model using photoactivated composite of methylene blue and gold nanoparticle

Publication date: Available online 27 May 2016
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Abeer Attia Tawfik, Islam Noaman, Hasan El-Elsayyad, Noha El-Mashad, Mona Soliman
BackgroundOnychomycosis is a widespread public health problem, in which t.rubrum and t.mentagrophytes is the commenest causative organisms. Current medical therapy has many drawbacks and side effects. Methylene blue (m.b) photodynamic therapy (pdt) proved efficacy but with lengthy sessions.ObjectivesOptimizing methylene blue photodynamic therapy by combination of methylene blue photosensitizer and gold nanoparticles (aunps) in a composite as gold nanoparticles are efficient delivery systems and efficient enhancers of photosensitizers for antifungal photodynamic therapy.Materials and methodsEighty newzealand rabbit (oryctolagus cuniculus) were used and categorized in eight equal groups as follows; healthy and infection control, composite photodynamic therapy and five comparative groups. Photodynamic therapy was initiated at day three to five post inoculation, for four sessions forty eight hours apart. Each group divided and light exposure at two fluencies; 80joules and 100 joules. All groups were investigated macroscopically and microscopically (histopathology and scanning electron microscope) also flowcytometry assessment for cell death and x-ray analysis for gold nanoparticles accumulation in brain and liver tissues were determined.ResultsRecovery from infection approaching 96% in gold nanoparticles+light group, around 40% in methylene blue photodynamic therapy and 34% in composite photodynamic therapy. The observed findings confirmed by apparent decrease of apoptosis, however small amounts of gold nanoparticles detected in brain and liver.ConclusionLight stimulated gold nanoparticles is a promising tool in treatment of onychomycosis.



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Genetic mutations in high grade gliomas of the adult spinal cord

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A Dilemma in Stroke Application: Standard or Modified Motor Unit Number Index?

Publication date: Available online 28 May 2016
Source:Clinical Neurophysiology
Author(s): Ping Zhou, Xiaoyan Li, Sheng Li, Sanjeev D. Nandedkar




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The survival outcome and prognostic factors for distal cholangiocarcinoma following surgical resection: a meta-analysis for the 5-year survival

Abstract

Purpose

To assess the available evidence on the prognostic factors for the 5-year survival for patients with distal cholangiocarcinoma (DCC) following surgical resection.

Methods

We performed a comprehensive search of abstracts included in databases where relevant studies were published between January 2000 and August 2015. Risk ratios (RRs), 95 % confidence intervals (95 % CIs), and random-effects model were calculated using RevMan 5.3 software.

Results

A total of 23 observational studies involving 2063 patients with DCC were analyzed. The meta-analysis showed that postoperative adjuvant chemotherapy was not confirmed as a prognostic factor, with similar 5-year survival rates between those receiving and not receiving chemotherapy (RR 0.71; 95 % CI 0.21–2.36; P = 0.57). Perineural invasion (RR 0.51; 95 % CI 0.40–0.64; P < 0.00001), lymph node metastasis (RR 0.51; 95 % CI 0.38–0.70; P < 0.0001), positive resection margin status (RR 2.11; 95 % CI 1.36–3.30; P = 0.001), and not-well-differentiated adenocarcinoma (RR 1.77; 95 % CI 1.39–2.25; P < 0.00001) were associated with shorter survival.

Conclusions

Perineural invasion, lymph node metastasis, resection margin status, and tumor differentiation were the significant prognostic factors for the 5-year survival.

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Web-based information on the treatment of oral leukoplakia – quality and readability

Objective

To categorise the content and assess the quality and readability of the online information regarding the treatment for oral leukoplakia.

Methods

An online search using the term 'leukoplakia treatment' was carried out on 8th June 2015 using the Google search engine. The content, quality and readability of the first 100 sites were explored. The quality of the web information was assessed using the following tools, the DISCERN instrument and the Journal of the American Medical Association (JAMA) benchmarks for website analysis and the HON seal. Readability was assessed via the Flesch Reading Ease Score.

Results

The search strategy generated 357 000 sites on the Google search engine. Due to duplicate links, non-operating links and irrelevant links, a total of 47 of the first 100 websites were included in this study. The mean overall rating achieved by included websites using the DISCERN instrument was 2.3. With regard to the JAMA benchmarks, the vast majority of examined websites (95.7%) completely fulfilled the disclosure benchmark and less than 50% of included websites met the three remaining criteria. A mean total readability score of 47.5 was recorded with almost 90% of websites having a readability level ranging from fairly difficult to very difficult.

Conclusion

Based on this study, the online health information regarding oral leukoplakia has challenging readability with content of questionable accuracy. As patients often search for health information online, it would be prudent for clinicians to highlight the caution with which online information should be interpreted.

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The choice of multi-beam IMRT for whole breast radiotherapy in early-stage right breast cancer

The aim of this study was to identify a rational strategy for the selection of multi-beam IMRT in patients with right breast cancer through the comparison of dosimetric parameters of the planning target volume...

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Too little is understood about head and neck cancer by those who make decisions about it

Publication date: June 2016
Source:British Journal of Oral and Maxillofacial Surgery, Volume 54, Issue 5
Author(s): David A. Mitchell




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Stability and complications of miniplates for mandibular reconstruction with a fibular graft: outcomes for 544 patients

Publication date: June 2016
Source:British Journal of Oral and Maxillofacial Surgery, Volume 54, Issue 5
Author(s): Shang-Ping Liu, Zhi-Gang Cai, Jie Zhang, Jian-Guo Zhang, Yi Zhang
Fibular flaps are usually used for the reconstruction of the mandible, but the use of plate systems, including miniplates and reconstruction plates, has recently been debated. We have made a retrospective study of 544 consecutive patients who had fibular grafts with miniplates used for fixation, and also made retrospective measurements of orthopantomographs from 37 patients to assess the stability of the miniplates used in the fibular flaps. When miniplates were used with fibular flaps there were 10.3% (56/544) complications, of which 4.8% (26/544) were loosening of the screws, 2.6% (14/544) fracture of the plate, 1.5% (8/544) exposure of the plate, and 6.4% (35/544) infection. The median (IQR) time at which the complications occurred was 24 (7–48) months. We conclude that loosening of screws is common at the binding interface near the condyle and in the molar region; plates are more likely to fracture near the binding interface in proximity to the molar region; and plates at the chin are the most likely to be exposed. Diabetes and the use of radiotherapy were associated with complications. Our data suggest that miniplates used for mandibular reconstruction are relatively reliable.



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Editorial Board

Publication date: June 2016
Source:British Journal of Oral and Maxillofacial Surgery, Volume 54, Issue 5





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Training Groups

Publication date: June 2016
Source:British Journal of Oral and Maxillofacial Surgery, Volume 54, Issue 5





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Plant-growth regulators alter phytochemical constituents and pharmaceutical quality in Sweet potato (Ipomoea batatas L.)

Sweet potato (Ipomoea batatas L.) is one of the most important consumed crops in many parts of the world because of its economic importance and content of health-promoting phytochemicals.

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A Fucus vesiculosus extract inhibits estrogen receptor activation and induces cell death in female cancer cell lines

We previously reported the anti-estrogenic activity of the brown seaweed, Fucus vesiculosus. The present study aimed to further investigate its anti-estrogenic modes of action and to assess other potentially biol...

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