Histochemical analysis of collagen fibers in giant cell fibroma and inflammatory fibrous hyperplasia

Publication date: Available online 28 April 2016
Source:Acta Histochemica
Author(s): Mônica Jarema Schmidt, André Tschoeke, Lúcia Noronha, Rafaela Scariot de Moraes, Ricardo Alves Mesquita, Ana Maria Trindade Grégio, Luciana Reis Azevedo Alanis, Sérgio Aparecido Ignácio, Jean Nunes dos Santos, Antonio Adilson Soares de Lima, Teixeira Suelen Luiz, Arielli Carine Michels, Maria Cássia Ferreira Aguiar, Aline Cristina Batista Rodrigues Johann
ObjectiveThe aim was to investigate collagen fibers in giant cell fibroma, inflammatory fibrous hyperplasia, and oral normal mucosa.Materials and methodsSixty-six cases were stained with picrosirius red. The slides were observed under polarization, followed by the measurement of the area and the percentage of the type I and type III collagens. The age and gender were obtained from the clinical records.ResultsNo differences could be observed in both the area and percentage of the type I and type III collagens within the categories of lesions and normal mucosa. In the giant cells fibroma, a greater area and percentage of type I collagen could be identified in individuals of less than 41.5 years (p<0.05).ConclusionThe distribution of type I and type III collagen fibers in the studied lesions followed a similar pattern to that observed in the normal mucosa, indicating a normal collagen maturation process of type III to I. The study supports that multinucleated and stellate cells of the giant cell fibroma appear to be functional within collagen types III and I turnover. The greater amount of type I collagen identified in giant cell fibroma in individuals of less than 41.5 years reinforce the neoplastic nature of lesion.



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Effect of chronic intake of liquid nutrition on stomach and duodenum morphology

Publication date: Available online 27 April 2016
Source:Acta Histochemica
Author(s): Michaela Vrabcova, Livia Mikuska, Rastislav Vazan, Michal Miko, Ivan Varga, Boris Mravec
Changes in the quantity and/or quality of food intake have been shown to be associated with morphological and functional alterations of the gastrointestinal system. To examine this, we investigated the effect of chronic liquid nutrition intake (Fresubin) on stomach and duodenum morphology in Wistar rats fed liquid nutrition during different developmental periods. We used four groups of rats: a) control group (CON) fed pelleted chow for 130days; b) liquid nutrition group (LN) fed liquid nutrition for 130days; c) liquid nutrition juvenile group (LNJ) fed liquid nutrition for 70days and then pelleted food for 60days; d) liquid nutrition adult group (LNA) fed pelleted chow for 70days and then liquid nutrition for 60days. We found that LN and LNA rats showed a significant reduction of empty stomach mass compared to CON animals, while stomach and duodenal longitudinal muscle layer thickness did not differ between groups. Villus height was increased only in LNA animals, while villus width was increased in both LN and LNA rats. Crypt depth was reduced in LNJ. However, liquid nutrition intake did not affect villus height/crypt depth ratio, nor number of goblet cells. We found that chronic intake of liquid nutrition affects some morphological parameters of the stomach and duodenum but these changes were not homogenous between experimental groups. Interestingly, transition from liquid nutrition to solid food reversed the alterations of stomach weight as well as villus width induced by intake of liquid nutrition in LNA rats. Our data indicate that morphological and functional changes in the gastrointestinal system induced by qualitative and quantitative changes in food intake are at least partially reversible. Therefore, specific diets may be used potentially as adjuvant treatment for modulating the progression of gastrointestinal diseases by affecting stomach and small intestine morphology.



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Protective role of garlic oil against oxidative damage induced by furan exposure from weaning through adulthood in adult rat testis

Publication date: Available online 26 April 2016
Source:Acta Histochemica
Author(s): Gehan El-Akabawy, Neveen M. El-Sherif
Furan is produced in a wide variety of heat-treated foods via thermal degradation. Furan contamination is found to be relatively high in processed baby foods, cereal products, fruits juices, and canned vegetables. Several studies have demonstrated that furan is a potent hepatotoxin and hepatocarcinogen in rodents. However, few studies have investigated the toxic effects of furan in the testis. In addition, the exact mechanism(s) by which furan exerts toxicity in the testis has not been fully elucidated. In this study, we investigated the potential of furan exposure from weaning through adulthood to induce oxidative stress in adult rat testis, as well as the potential of garlic oil (GO) to ameliorate the induced toxicity. Our results reveal that furan administration significantly reduced serum testosterone levels and increased the levels of malondialdehyde (MDA); furthermore, furan administration decreased significantly the enzymatic activity of testicular antioxidants, including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) and induced histopathological alterations in the testis. GO co-administration ameliorated the reduction in testosterone levels and dramatically attenuated the furan-induced oxidative and histopathological changes. In addition, Go significantly down-regulated the increased caspase-3 and cytochrome P450 2E1 (CYP2E1) expression in the furan-treated testis. To the best of our knowledge, this study is the first to demonstrate the furan-induced oxidative changes in the adult rat testis and the protective role of GO to ameliorate these changes through its antioxidant effects and its ability to inhibit CYP2E1 production.



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Androgen receptor-mediated non-genomic effects of vinclozolin on porcine ovarian follicles and isolated granulosa cells

Publication date: Available online 16 April 2016
Source:Acta Histochemica
Author(s): Kamil Wartalski, Malgorzata Knet-Seweryn, Dorota Hoja-Lukowicz, Zbigniew Tabarowski, Malgorzata Duda
The present study investigated the influence of the androgen receptor (AR) agonists testosterone (T) and dihydrotestosterone (DHT), and vinclozolin (Vnz), a fungicide with antiandrogenic activity, on non-genomic signal transduction within ovarian follicles. Porcine granulosa cells (GCs) isolated from mature follicles were cultured for 48h. For the last 24h of culture, they were exposed to T (10⁻⁷M), DHT (10⁻⁷M), Vnz (1.4×10⁻⁵M), T and Vnz (T+Vnz), or DHT and Vnz (DHT+Vnz) at the same concentrations. To better imitate in vivo conditions, whole follicles (4–6mm in diameter) were incubated (24h) in an organ culture system with the same factors. Expression of AR mRNA and protein was determined by real-time PCR and western blot analyses. To demonstrate AR localization in cultured GCs and whole follicles, immunocytochemistry and immunohistochemistry were performed, respectively. To elucidate the possible non-genomic action of Vnz in GCs, protein expression and the activity of ERK1/2 and Akt kinases were determined by western blot and ELISA analyses. The immunocytochemistry and immunohistochemistry results showed that exposure of GCs and follicles to Vnz resulted in cytoplasmic and perinuclear AR localization. Real-time PCR and western blot analysis showed that AR mRNA and protein expression increased (P≤0.001) in GC cultures after combined treatment with an androgen and Vnz. In whole follicles, such treatment also increased AR mRNA with a decrease in the respective protein expression (P≤0.001). Moreover, addition of T or DHT with Vnz increased the activity of ERK1/2 and Akt kinases in cultured GCs (P≤0.001). The results suggest a novel mechanism for Vnz action in porcine ovarian follicles on both AR mRNA and protein levels. Thus, this environmental antiandrogen activates non-genomic signaling pathways, as indicated by the increased activity of both investigated kinases observed within minutes of Vnz addition. Given the widespread presence of Vnz in the environment, elucidation of its non-genomic action should be the subject of studies on female fertility.



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Evidence for CD34/SMA positive cells in the left main coronary artery in atherogenesis

Publication date: Available online 14 April 2016
Source:Acta Histochemica
Author(s): Peter Kruzliak, David L. Hare, Peter Sabaka, Delian Delev, Ludovit Gaspar, Luis Rodrigo, Anthony Zulli
Regression of atherosclerosis is a key aspect of preventing further coronary artery disease and understanding which cell type forms smooth muscle cells in atherosclerotic fibrous caps will aid in reducing CAD. Atherogenesis is a complex interplay of cells migrating and proliferating into the vascular wall. CD34 positive hemapoetic stem cells are believed to not transform into vascular smooth muscle cells (SMC). The current study hypothesised that there would be no evidence for CD34⁺/α SMC actin⁺ cells in atherosclerotic coronary arteries. Aims: To identify CD34+/α actin positive cells in the fibrous cap and wall of atherosclerotic plaques in the coronary artery. Methods: Male New Zealand White rabbits were fed a diet containing 0.5% cholesterol and 1% methionine for 4 weeks, then 9 weeks of normal diet to induce regression. Immunohistochemistry was used to detect CD34⁺ haematopoietic progenitor cells and α SMC actin. Results: In the fibrous cap, the majority of cells were CD34⁻/α SMC actin⁺ spindle shaped cells. However very rare populations of CD34⁺/α SMC actin⁺ and CD34⁺/α SMC actin⁻ cells were also present but these cells were not spindle shaped. Conclusion: Our study found that CD34⁺/α SMC actin⁻ spindle shaped cells were absent from the fibrous cap. Moreover, the predominant cell population were the vascular smooth muscle cells (CD34⁻/α SMC actin⁺) but (CD34⁺/α SMC actin⁺) cells were also present. This model could be used to understand the role of each SMC population subtype to hasten atherosclerotic regression in the coronary artery.



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Expression of calbindin-D9k and vitamin D receptor in the uterus of Egyptian buffalo during follicular and luteal phases

Publication date: Available online 30 April 2016
Source:Acta Histochemica
Author(s): Mahmoud Abdelghaffar Emam, Mahmoud E.A. Abouelroos, Fatma A. Gad
Uteri of mature Egyptian buffalo cows (5–10 years old) were collected at follicular (n=12) and luteal (n=16) phases of estrous cycle to investigate the expression of calbindin-D9k (CaPB-9k) and vitamin D receptor (VDR). This study was done using avidin-biotin immunohistochemistry method. In addition, blood levels of calcium (Ca), vitamin D3 (Vit D), estrogen (E2) and progesterone (P4) were measured. The immunohistochemical findings restricted the expressions of CaBP-9k and VDR to the luminal and glandular epithelia of the endometrium implicating the importance of CaBP-9K and VDR in the function of endometrial epithelium, especially the glandular one, in order to prepare a receptive uterus. On the other hand, the myometrium did not express CaBP-9k or VDR that denies the potential role of CaBP-9k and VDR in the uterine contractility during the estrous cycle of Egyptian buffalo. All of Ca, Vit D, and P4 blood levels significantly (P<0.05) increased during luteal phase however, blood level of E2 significantly (P<0.05) increased during follicular phase. The expressions of CaBP-9k and VDR in the uterus of Egyptian buffalo were significantly (P<0.05) higher during luteal (P4 dominant) phase than during the follicular (E2 dominant) phase indicating that P4 up-regulates the expressions of CaBP-9k and VDR. In view of these observations, this study represents the first characterization of CaBP-9K and VDR expression in the uterus of Egyptian buffalo and suggests the pivotal role of CaBP-9k and VDR in the uterine receptivity. Furthermore, it demonstrates the regulatory role of P4 for expressions of CaBP-9k and VDR in buffalo uterus.



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miR-128 regulates differentiation of hair follicle mesenchymal stem cells into smooth muscle cells by targeting SMAD2

Publication date: Available online 14 April 2016
Source:Acta Histochemica
Author(s): Zhihao Wang, Li Pang, Huiying Zhao, Lei Song, Yuehui Wang, Qi Sun, Chunjie Guo, Bin Wang, Xiujiao Qin, Aiqun Pan
Human hair follicle mesenchymal stem cells (hHFMSCs) are an important source of cardiovascular tissue engineering for their differentiation potential into smooth muscle cells (SMCs), yet the molecular pathways underlying such fate determination is unclear. MicroRNAs (miRNAs) are non-coding RNAs that play critical roles in cell differentiation. In present study, we found that miR-128 was remarkably decreased during the differentiation of hHFMSCs into SMCs induced by transforming growth factor-β1 (TGF-β1). Moreover, overexpression of miR-128 led to decreased expression of SMC cellular marker proteins, such as smooth muscle actin (SMA) and calponin, in TGF-β1-induced SMC differentiation. Further, we identified that miR-128 targeted the 3′-UTR of SMAD2 transcript for translational inhibition of SMAD2 protein, and knockdown of SMAD2 abrogated the promotional effect of antagomir-128 (miR-128 neutralizer) on SMC differentiation. These results suggest that miR-128 regulates the differentiation of hHFMSCs into SMCs via targeting SMAD2, a main transcription regulator in TGF-β signaling pathway involving SMC differentiation. The miR-128/SMAD2 axis could therefore be considered as a candidate target in tissue engineering and regenerative medicine for SMCs.



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Mesenchymal stem cells differentiated into chondrocyte—Like cells

Publication date: Available online 14 April 2016
Source:Acta Histochemica
Author(s): Suteera Narakornsak, Naree Poovachiranon, Lamaiporn Peerapapong, Peeraphan Pothacharoen, Sirinda Aungsuchawan
Among the stem cells contained in human amniotic fluid (hAF), the human amniotic fluid derived-mesenchymal stem cells (hAF-MSCs) are derived from fetal membranes and tissues that are produced during fetal development. The aim of this study was to characterize the 'stem-ness' properties of hAF-MSCs and their potency with regard to the chondrogenic differentiations using the scaffold cultivation method. This study revealed that the easily accessed and isolated MSCs were highly cell prolific and there were fewer ethical concerns regarding their usage. The MSCs were studied through the use of the alamar blue technique. In addition, after cell isolation, hAF-MSCs displayed typical MSCs morphologies including MSCs biomarker characteristics and immune privilege properties (CD44, CD73, CD90, CD105 and HLA-ABC) through immunofluorescence and flow cytometry. Interestingly, this result indicated a negative expression when using the C-Kit (CD117, tyrosine kinase receptor type III ligand for cytokine stem cell factor). This expression can be found at the cell's surface of the amniotic fluid-derived stem cells (AFSCs). This study found evidence that hAF-MSCs had the ability to differentiate the cells into the chondrogenic lineage by exhibiting chondrogenic related genes and proteins (SOX9, AGC, COL2A1 and COMP) through RT-qPCR, immunoenzymatic assays and immunofluorescence analysis. Furthermore, MSCs presented sGAGs accumulation, which was confirmed by histological analysis and SEM. Therefore, this study showed that the MSCs characteristics are contained in AF and are of significant value for further research. It appears that MSCs possess the potential for use in treatments that would necessitate the use of regenerative cell therapy.



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Turkish propolis protects human endothelial cells in vitro from homocysteine-induced apoptosis

Publication date: Available online 13 April 2016
Source:Acta Histochemica
Author(s): Ekrem Darendelioglu, Gurkan Aykutoglu, Musa Tartik, Giyasettin Baydas
Chronic cardiovascular and neurodegenerative complications induced by hyperhomocysteinemia have been most relatively associated with endothelial cell injury. Elevated homocysteine (Hcy) generates reactive oxygen species (ROS) accompanying with oxidative stress which is hallmarks of the molecular mechanisms responsible for cardiovascular disease.Propolis is a natural product, obtained by honeybee from various oils, pollens, special resins and wax materials, conventionally used with the purpose of treatment by folks Propolis has various biological activities and powerful antioxidant capacity. The flavonoids and phenolic acids, most bioactive components of propolis, have superior antioxidant ability to defend cell from free radicals. This study was designed to examine the protective effects of Turkish propolis (from east of country) on Hcy induced ROS production and apoptosis in human vascular endothelial cells (HUVECs).According to results, co-treatment of HUVECs with propolis decreased Hcy-induced ROS overproduction and lipid peroxidation (LPO) levels. Furthermore, overproductions of Bax, caspase-9 and caspase-3 protein, elevation of cytochrome c release in Hcy-treated HUVECs were significantly reduced by propolis. It was concluded that propolis has cytoprotective ability against cytotoxic effects of high Hcy in HUVECs.



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Clusterin immunoexpression is associated with early stage endometrial carcinomas

Publication date: Available online 11 April 2016
Source:Acta Histochemica
Author(s): Jaudah Ahmed Al-Maghrabi, Nadeem Shafique Butt, Nisrin Anfinan, Khalid Sait, Hesham Sait, Osama Bajouh, Mohamad Nidal Khabaz
Clusterin has anti-apoptotic, regeneration and migration stimulating effects on tumor cells. This study investigates the relation between clusterin expression and the clinicopathological parameters in endometrial carcinomas. Seventy one cases of previously diagnosed endometrial carcinoma (including 59 endometrioid adenocarcinoma, 9 serous adenocarcinoma, 1 clear cell adenocarcinoma, and 2 malignant mixed Mullerian tumor) and 30 tissue samples of non-cancerous endometrium (including 16 proliferative endometrium, 10 secretory endometrium and 4 endometrial polyps) were employed for clusterin detection using tissue microarrays and immunostaining. A total number of 23 (32.4%) cases were positive for clusterin immunostaining. Brown granular cytoplasmic expression of clusterin was detected in 33.9% of endometrioid adenocarcinomas, 22.2% papillary serous endometrial carcinomas. Three (10%) control cases showed granular cytoplasmic expression. Positive clusterin immunostaining was found more frequent in well differentiated and stage I endometrial carcinomas, showing significant statistical association (p-value=0.036 and p-value=0.002 respectively). Significant difference in clusterin expression was observed between tumor cases and control group (P-Value=0.019), i.e., endometrial carcinoma cases are more than four times likely to show positive clusterin immunostaining (odds ratio 4.313 with 95% confidence interval 1.184–15.701). This study did not find relation between clusterin expression and disease recurrence, survival or any of the other clinicopathological parameters in endometrial tumors. The results of our study confirms the diagnostic values of clusterin in supporting the diagnosis of endometrioid carcinoma. When clusterin is expressed in endometrial tumors, it is associated with lower stage. The correlation of clusterin with tumor stage suggests involvement of this molecule in endometrial tumor progression.



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Cucumarioside A2-2 causes changes in the morphology and proliferative activity in mouse spleen

Publication date: Available online 11 April 2016
Source:Acta Histochemica
Author(s): E.A. Pislyagin, I.V. Manzhulo, P.S. Dmitrenok, D.L. Aminin
The immunomodulatory effect of triterpene glycoside cucumarioside A2-2 (CA2-2), isolated from the Far Eastern sea cucumber Cucumaria japonica, on the mouse spleen was investigated in comparison with lipopolysaccharide (LPS). It has been shown that the intraperitoneal (i.p.) glycoside administration did not influence on splenic weights, while the statistically significant increase in splenic weight was observed after LPS administration. Changes in the ratio of red to white pulp after CA2-2 or LPS administration were observed. The proportion of splenic white pulp after glycoside or LPS administration increased by up to 34% and 36%, respectively. A detailed study of the distribution of the РСNA (Proliferating Cell Nuclear Antigen) marker showed that the proliferative activity in the white pulp under CA2-2 and LPS influence increased 2.07 and 2.24 times, respectively. The localization of PCNA-positive nuclei in the white pulp region, as well as their dimensional characteristics, suggests that a large proportion of the proliferating cell population consisted of B cells. The mass spectrometry profiles of spleen peptide/protein homogenate were obtained using the MALDI-TOF-MS (Matrix −Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry) approach. It was found that i.p. stimulation of animals with CA2-2 or LPS leads to marked changes in the intensity of revealed characteristic peaks of peptides/proteins after exposure to immunostimulants.

Graphical abstract

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Histone epigenetic marks in heterochromatin and euchromatin of the Chagas’ disease vector, Triatoma infestans

Publication date: Available online 11 April 2016
Source:Acta Histochemica
Author(s): Elenice M. Alvarenga, Vera L.C.C. Rodrigues, Alberto S. Moraes, Luisa S. Naves, Mateus Mondin, Marina B. Felisbino, Maria Luiza S. Mello
Triatoma infestans, a vector of Chagas' disease, shows several particular cell biology characteristics, including the presence of conspicuous heterochromatic bodies (chromocenters) where DNA methylation has not been previously detected. Whether histone modifications contribute to the condensed state of these bodies has not yet been studied. Here, we investigated epigenetic modifications of histones H3 and H4 and presence of the non-histone heterochromatin protein (HP1-α) in the chromocenters and euchromatin of T. infestans cell nuclei, using immunocytochemistry. The effect of different concentrations of the histone deacetylase inhibitors valproic acid (VPA) and sodium butyrate (NaBt) on chromocenter condensation was visually examined; in VPA-treated specimens, this effect was also analyzed by image analysis. Trimethylated H3K9 signals, which were revealed in chromocenter and non-chromocenter areas, were strongest in chromocenters, whereas selected acetylated histone marks and mono- and dimethylated H3K9 and H4K20 signals were detected only in euchromatin. Weak trimethylated H4K20 signals and variable distribution of HP1-α were detected in chromocenters of part of the cellular population analyzed. Although specific VPA and NaBt treatment conditions affected the heterochromatin condensation pattern, they did not induce a decrease in survival and molting rates of the T. infestans nymphs. The VPA-induced chromatin remodeling was not accompanied by induction of H3K9 acetylation in chromocenters. Present findings regarding histone modifications and effects following VPA or NaBt treatments did not yet solve the question of which factors are responsible for maintenance of the condensed state of chromocenters in T. infestans. A possibility requiring further investigation remains on histone methylation marks and/or non-histone proteins.



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MicroRNA-193b inhibits the proliferation, migration and invasion of gastric cancer cells via targeting cyclin D1

Publication date: Available online 9 April 2016
Source:Acta Histochemica
Author(s): Lanlan Wang, Yuanyuan Zhang, Lijun Zhao, Siqi Liu, Shashuang Yu, Yanni Ma, Guotao Sun
MicroRNAs have been involved in RNA silencing and post-transcriptional regulation of gene expression and also play important roles in tumorigenesis and tumor progression. MiR-193b was previously reported to act as tumor suppressor in diverse cancers. However, little is known about the expression, function and mechanism of miR-193b in gastric cancer (GC). In this study, we investigated the expression of miR-193b in 50 GC cases and found that miR-193b was significantly reduced in GC tissues compared with the adjacent normal gastric tissues. Moreover, lower-level of miR-193b was also associated with a more aggressive GC phenotype. We further demonstrated that miR-193b can inhibit the proliferation, migration and invasion of HGC-27 and MGC-803 GC cells. Further mechanism study indicated that CCND1 was a direct target of miR-193b in GC. Overexpression of miR-193b inhibited the expression of CCND1, and knock-down of CCND1 inhibited the proliferation of GC cells, suggesting that miR-193b exerted its anti-tumorigenic role in GC cells through targeting CCND1 gene.



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A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression.

Mogg, A; Pluck, G; Eranti, SV; Landau, S; Purvis, R; Brown, RG; Curtis, V; Mogg, A; Pluck, G; Eranti, SV; Landau, S; Purvis, R; Brown, RG; Curtis, V; Howard, R; Philpot, M; McLoughlin, DM; - view fewer (2008) A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. Psychol Med , 38 (3) pp. 323-333. 10.1017/S0033291707001663 .

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ProTides of N-(3-(5-(2′-deoxyuridine))prop-2-ynyl)octanamide as potential anti-tubercular and anti-viral agents

McGuigan, C; Derudas, M; Gonczy, B; Hinsinger, K; Kandil, S; Pertusati, F; Serpi, M; McGuigan, C; Derudas, M; Gonczy, B; Hinsinger, K; Kandil, S; Pertusati, F; Serpi, M; Snoeck, R; Andrei, G; Balzarini, J; McHugh, TD; Maitra, A; Akorli, E; Evangelopoulos, D; Bhakta, S; - view fewer (2014) ProTides of N-(3-(5-(2′-deoxyuridine))prop-2-ynyl)octanamide as potential anti-tubercular and anti-viral agents. Bioorganic and Medicinal Chemistry , 22 (9) pp. 2816-2824. 10.1016/j.bmc.2014.02.056 .

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Psychological processes underlying delusional thinking in late-onset psychosis: a preliminary investigation.

McCulloch, Y; Clare, L; Howard, R; Peters, E; (2006) Psychological processes underlying delusional thinking in late-onset psychosis: a preliminary investigation. Int J Geriatr Psychiatry , 21 (8) pp. 768-777. 10.1002/gps.1561 .

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Striatal dopamine (D2) receptor availability predicts socially desirable responding.

Reeves, SJ; Mehta, MA; Montgomery, AJ; Amiras, D; Egerton, A; Howard, RJ; Grasby, PM; (2007) Striatal dopamine (D2) receptor availability predicts socially desirable responding. Neuroimage , 34 (4) pp. 1782-1789. 10.1016/j.neuroimage.2006.10.042 .

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Brain mechanisms of successful compensation during learning in Alzheimer disease.

Gould, RL; Arroyo, B; Brown, RG; Owen, AM; Bullmore, ET; Howard, RJ; (2006) Brain mechanisms of successful compensation during learning in Alzheimer disease. Neurology , 67 (6) pp. 1011-1017. 10.1212/01.wnl.0000237534.31734.1b .

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Delusional experience of self as receiver of email in schizoaffective disorder.

Raczek, M; Howard, R; (2007) Delusional experience of self as receiver of email in schizoaffective disorder. Int J Geriatr Psychiatry , 22 (5) pp. 496-497. 10.1002/gps.1757 .

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Abuse of vulnerable people with dementia by their carers: can we identify those most at risk?

Cooney, C; Howard, R; Lawlor, B; (2006) Abuse of vulnerable people with dementia by their carers: can we identify those most at risk? Int J Geriatr Psychiatry , 21 (6) pp. 564-571. 10.1002/gps.1525 .

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TWiV 387: Quaxxed

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, and 

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Prostaglandin-E1 has a protective effect on renal ischemia/reperfusion-induced oxidative stress and inflammation mediated gastric damage in rats

Publication date: July 2016
Source:International Immunopharmacology, Volume 36
Author(s): Selda Gezginci-Oktayoglu, Nurcan Orhan, Sehnaz Bolkent
Gastrointestinal complications are frequent in renal transplant recipients. In this regard, renal ischemia/reperfusion injury (IRI)-induced gastric damage seems to be important and there is no data available on the mechanism of this pathology. Because of its anti-inflammatory and anti-oxidant properties, it can be suggested that prostaglandin-E1 (PGE1) protects cells from renal IRI-induced gastric damage. The aim of this study was to investigate the molecular mechanisms of gastric damage induced by renal IRI and the effect of PGE1 on these mechanisms. We set an experiment with four different animal groups: physiological saline-injected and sham-operated rats, PGE1 (20μg/kg)-administered and sham operated rats, renal IRI subjected rats, and PGE1-administered and renal IRI subjected rats. The protective effect of PGE1 on renal IRI-induced gastric damage was determined based on reduced histological damage and lactate dehydrogenase activity. Moreover, we demonstrated that PGE1 shows its protective effect through reducing the production of reactive oxygen species and malondialdehyde levels. During histological examination, we observed the presence of common mononuclear cell infiltration. Therefore, pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β levels were measured and it has been shown that PGE1 suppressed both cytokines. Furthermore, it was found that PGE1 reduced the number of NF-κB⁺ and caspase-3⁺ inflammatory cells, and also NF-κB DNA-binding activity, while increasing proliferating cell nuclear antigen⁺ epithelial cells in the stomach tissue of rats subjected to renal IR. Our data showed that PGE1 has a protective effect on renal IRI-induced oxidative stress and inflammation mediated gastric damage in rats.



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Development of a novel monoclonal antibody to human inducible co-stimulator ligand (ICOSL): Biological characteristics and application for enzyme-linked immunosorbent assay

Publication date: July 2016
Source:International Immunopharmacology, Volume 36
Author(s): Xiaohan Hu, Jian Wu, Jingnan An, Yumin Hu, Yu Shen, Cuiping Liu, Xueguang Zhang
ICOSL (B7-H2, CD275), a co-stimulatory molecule of the B7 superfamily, functions as a positive signal in immune response. To investigate whether ICOSL could be released into sera and the possible biological function of soluble ICOS (sICOSL), we generated and characterized a functional anti-human ICOSL monoclonal antibody (mAb), 20B10, and developed a novel enzyme-linked immunosorbent assay (ELISA) based on two anti-human ICOSL antibodies with different epitope specificities. Using the ELISA system, we found that sICOSL in the serum of healthy donors increases in an age-dependent manner and that the matrix metalloproteinase inhibitor (MMPI) could suppress sICOSL production. Together, these data demonstrate that the existence of circulating sICOSL in human serum might play an important role in immunoregulation.



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Neotuberostemonine attenuates bleomycin-induced pulmonary fibrosis by suppressing the recruitment and activation of macrophages

Publication date: July 2016
Source:International Immunopharmacology, Volume 36
Author(s): Juan Xiang, Si Cheng, Tianlong Feng, Yan Wu, Weina Xie, Mian Zhang, Xianghong Xu, Chaofeng Zhang
Neotuberostemonine (NTS) is one of the main antitussive alkaloids in the root of Stemona tuberosa Lour. This study aimed to investigate the effects of NTS on bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism. After BLM administration, NTS were orally administered to mice at 20 and 40mg/kg per day from days 8 to 21, with nintedanib as a positive control. The effect of NTS on BLM-induced mice was assessed via histopathological examination by HE and Masson's trichrome staining, TGF-β1 level and macrophage recruitment by immunohistochemical staining, expression of profibrotic media and M1/M2 polarization by western blot. RAW 264.7 cells were used to evaluate whether NTS (1, 10, 100μM) directly affected macrophages. The results revealed that NTS treatment significantly ameliorated lung histopathological changes and decreased inflammatory cell counts in the bronchoalveolar lavage fluid. The over-expression of collagen, α-SMA and TGF-β1 was reduced by NTS. Furthermore, NTS markedly lowered the expression of MMP-2 and TIMP-1 while raised the expression of MMP-9. A further analysis showed that NTS was able to decrease the recruitment of macrophages and to inhibit the M2 polarization in mice lung tissues. The experiment in vitro showed that NTS significantly reduced the arginase-1 (marker for M2) expression in a dose-dependent manner but down-regulated the iNOS (marker for M1) expression only at 100μM. In conclusion, our study demonstrated for the first time that NTS has a significant protective effect on BLM-induced pulmonary fibrosis through suppressing the recruitment and M2 polarization of macrophages.

Graphical abstract

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High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats

Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia-induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats.

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Local trauma in human patellar tendon leads to widespread changes in the tendon gene expression

Low cellular activity and slow tissue turnover in human tendon may prolong resolution of tendinopathy. This may be stimulated by moderate localized traumas such as needle penetrations, but whether this results in a widespread cellular response in tendons is unknown. In an initial hypothesis-generating study, a trauma-induced tendon cell activity (increased total RNA and collagen I mRNA) was observed after repeated patellar tendon biopsies in young men. In a subsequent controlled study, 25 young men were treated with two 0.8-mm-diameter needle penetrations [n = 13, needle-group (NG)] or one 2.1-mm-diameter needle biopsy [n = 12, biopsy-group (BG)] in one patellar tendon. Four weeks later biopsies were taken from treated (5 mm lateral from trauma site) and contralateral tendons for analyses of RNA content (ribogreen assay), DNA content (PCR based), and gene expression for relevant target genes (Real-time RT-PCR) (NG, n = 11 and BG, n = 8). Intervention increased RNA content, and mRNA expression of collagen I and III and TGF-β1 (P < 0.05), with biopsy treatment having greatest effect (tendency for RNA and collagen I). Results for DNA content were inconclusive, and no changes were detected in expression of insulin-like growth factor-I, connective tissue growth factor, scleraxis, decorin, fibromodulin, tenascin-C, tenomodulin, VEGFa, CD68, IL-6, MMP12, and MMP13. In conclusion, a moderate trauma to a healthy human tendon (e.g., biopsy sampling) results in a widespread upregulation of tendon cell activity and their matrix protein expression. The findings have implications for design of studies on human tendon and may provide perspectives in future treatment strategies in tendinopathy.

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Nitric oxide-mediated vascular function in sepsis using passive leg movement as a novel assessment: a cross-sectional study

Post-cuff occlusion flow-mediated dilation (FMD) is a proposed indicator of nitric oxide (NO) bioavailability and vascular function. FMD is reduced in patients with sepsis and may be a marker of end organ damage and mortality. However, FMD likely does not solely reflect NO-mediated vasodilation, is technically challenging, and often demonstrates poor reproducibility. In contrast, passive leg movement (PLM), a novel methodology to assess vascular function, yields a hyperemic response that is predominately NO-dependent, reproducible, and easily measured. This study evaluated PLM as an approach to assess NO-mediated vascular function in patients with sepsis. We hypothesized that PLM-induced hyperemia, quantified by the increase in leg blood flow (LBF), would be attenuated in sepsis. In a cross-sectional study, 17 subjects in severe sepsis or septic shock were compared with 16 matched healthy controls. Doppler ultrasound was used to assess brachial artery FMD and the hyperemic response to PLM in the femoral artery. FMD was attenuated in septic compared with control subjects (1.1 ± 1.7% vs. 6.8 ± 1.3%; values are means ± SD). In terms of PLM, baseline LBF (196 ± 33 ml/min vs. 328 ± 20 ml/min), peak change in LBF from baseline (133 ± 28 ml/min vs. 483 ± 86 ml/min), and the LBF area under the curve (16 ± 8.3 vs. 143 ± 33) were all significantly attenuated in septic subjects. Vascular function, as assessed by both FMD and PLM, is attenuated in septic subjects compared with controls. These data support the concept that NO bioavailability is attenuated in septic subjects, and PLM appears to be a novel and feasible approach to assess NO-mediated vascular function in sepsis.

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A standard, single dose of inhaled terbutaline attenuates hyperpnea-induced bronchoconstriction and mast cell activation in athletes

Release of bronchoactive mediators from mast cells during exercise hyperpnea is a key factor in the pathophysiology of exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effect of a standard, single dose of an inhaled β₂-adrenoceptor agonist on mast cell activation in response to dry air hyperpnea in athletes with EIB. Twenty-seven athletes with EIB completed a randomized, double-blind, placebo-controlled, crossover study. Terbutaline (0.5 mg) or placebo was inhaled 15 min prior to 8 min of eucapnic voluntary hyperpnea (EVH) with dry air. Pre- and postbronchial challenge, urine samples were analyzed by enzyme immunoassay for 11β-prostaglandin F_2α (11β-PGF_2α). The maximum fall in forced expiratory volume in 1 s of 14 (12–20)% (median and interquartile range) following placebo was attenuated to 7 (5–9)% with the administration of terbutaline (P < 0.001). EVH caused a significant increase in 11β-PGF_2α from 41 (27–57) ng/mmol creatinine at baseline to 58 (43–72) ng/mmol creatinine at its peak post-EVH following placebo (P = 0.002). The rise in 11β-PGF_2α was inhibited with administration of terbutaline: 39 (28–44) ng/mmol creatinine at baseline vs. 40 (33–58) ng/mmol creatinine at its peak post-EVH (P = 0.118). These data provide novel in vivo evidence of mast cell stabilization following inhalation of a standard dose of terbutaline prior to bronchial provocation with EVH in athletes with EIB.

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Cardiorespiratory fitness estimation using wearable sensors: Laboratory and free-living analysis of context-specific submaximal heart rates

In this work, we propose to use pattern recognition methods to determine submaximal heart rate (HR) during specific contexts, such as walking at a certain speed, using wearable sensors in free living, and using context-specific HR to estimate cardiorespiratory fitness (CRF). CRF of 51 participants was assessed by a maximal exertion test (Vo_{2 max}). Participants wore a combined accelerometer and HR monitor during a laboratory-based simulation of activities of daily living and for 2 wk in free living. Anthropometrics, HR while lying down, and walking at predefined speeds in laboratory settings were used to estimate CRF. Explained variance (R²) was 0.64 for anthropometrics, and increased up to 0.74 for context-specific HR (0.73-0.78 when including fat-free mass). Next, we developed activity recognition and walking speed estimation algorithms to determine the same contexts (i.e., lying down and walking) in free living. Context-specific HR in free living was highly correlated with laboratory measurements (Pearson's r = 0.71–0.75). R² for CRF estimation was 0.65 when anthropometrics were used as predictors, and increased up to 0.77 when including free-living context-specific HR (i.e., HR while walking at 5.5 km/h). R² varied between 0.73 and 0.80 when including fat-free mass among the predictors. Root mean-square error was reduced from 354.7 to 281.0 ml/min by the inclusion of context-specific HR parameters (21% error reduction). We conclude that pattern recognition techniques can be used to contextualize HR in free living and estimated CRF with accuracy comparable to what can be obtained with laboratory measurements of HR response to walking.

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Bronchodilating effect of deep inspirations in asthma and chronic cough

The pathophysiologic processes distinguishing classic asthma (CA), cough-variant asthma (CVA), and methacholine (MCh)-induced cough but normal airway sensitivity (COUGH) are inadequately understood and may be a result of differences in the ability to bronchodilate following a deep inspiration (DI). The purpose of this study was to compare the bronchodilating effect of DIs in individuals with CA, CVA, and COUGH using high-dose MCh. Individuals aged 18-65 yr with CA or suspected CVA completed high-dose MCh testing to a maximum change in forced expiratory volume in 1 s (FEV₁) of 50% from baseline (MAX). Impulse oscillometry (IOS) measurements and partial and maximal-flow volume curves (used to calculate a DI index) were recorded at baseline and at each dose of MCh. Body plethysmography was performed at baseline and MAX. Twenty-eight subjects [25 women, 39.8 ± 11.9 yr (means ± SD)] were studied (n = 11 CA, n = 10 CVA, and n = 7 COUGH). At MAX, the percent change in FEV₁ was greater in subjects with CA compared with those with CVA (P < 0.001) and COUGH (P < 0.001), and the percent change in forced vital capacity was greater in those with CA than with COUGH (P = 0.017). Subjects with CA and CVA developed dynamic hyperinflation and gas trapping. In subjects with CA and CVA, all IOS parameters were significantly increased from baseline to MAX, except for central respiratory resistance (R20). In individuals with COUGH, total respiratory resistance, R20, and resonant frequency were significantly increased from baseline. At MAX, the DI index was positive in all groups, suggesting preserved bronchodilation (CA, 0.67 ± 0.97; CVA, 0.51 ± 0.73; COUGH, 0.01 ± 0.36; P = 0.211). We conclude that the bronchodilating effect of DIs is preserved in individuals with CA, CVA, and borderline with COUGH; however, hyperinflation and gas trapping are avoided in subjects with COUGH alone.

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Temperature and blood flow distribution in the human leg during passive heat stress

The influence of temperature on the hemodynamic adjustments to direct passive heat stress within the leg's major arterial and venous vessels and compartments remains unclear. Fifteen healthy young males were tested during exposure to either passive whole body heat stress to levels approaching thermal tolerance [core temperature (T_c) + 2°C; study 1; n = 8] or single leg heat stress (T_c + 0°C; study 2; n = 7). Whole body heat stress increased perfusion and decreased oscillatory shear index in relation to the rise in leg temperature (T_leg) in all three major arteries supplying the leg, plateauing in the common and superficial femoral arteries before reaching severe heat stress levels. Isolated leg heat stress increased arterial blood flows and shear patterns to a level similar to that obtained during moderate core hyperthermia (T_c + 1°C). Despite modest increases in great saphenous venous (GSV) blood flow (0.2 l/min), the deep venous system accounted for the majority of returning flow (common femoral vein 0.7 l/min) during intense to severe levels of heat stress. Rapid cooling of a single leg during severe whole body heat stress resulted in an equivalent blood flow reduction in the major artery supplying the thigh deep tissues only, suggesting central temperature-sensitive mechanisms contribute to skin blood flow alone. These findings further our knowledge of leg hemodynamic responses during direct heat stress and provide evidence of potentially beneficial vascular alterations during isolated limb heat stress that are equivalent to those experienced during exposure to moderate levels of whole body hyperthermia.

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Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias

Lung diffusing capacity for carbon monoxide (DL_CO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DL_CO to changes in alveolar membrane diffusive conductance (DM_CO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DL_NO) better reflects fibrotic changes than DL_CO. DL_NO-DL_CO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DM_CO and pulmonary capillary volume (V_C) were calculated. DL_NO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DL_CO was within the normal range in a nonnegligible number of patients. Both DL_NO and DL_CO were significantly correlated with visual assessment of fibrosis but DL_NO more closely than DL_CO. DM_CO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas V_C was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DL_NO may provide a more sensitive evaluation of fibrotic changes than DL_CO in either UIP-IPF or NSIP, because it better reflects DM_CO.

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Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA^Tph2–/–) rats. DA^Tph2–/– rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (~50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA^Tph2–/– rats. Body temperature was also maintained in adult DA^Tph2–/– rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA^Tph2–/– rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat.

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Fatigue-induced adjustment in antagonist coactivation by old adults during a steadiness task

The purpose of this study was to determine the adjustments in the level of coactivation during a steadiness task performed by young and old adults after the torque-generating capacity of the antagonist muscles was reduced by a fatiguing contraction. Torque steadiness (coefficient of variation) and electromyographic activity of the extensor and flexor carpi radialis muscles were measured as participants matched a wrist extensor target torque (10% maximum) before and after sustaining an isometric contraction (30% maximum) with wrist flexors to task failure. Time to failure was similar (P = 0.631) for young (417 ± 121 s) and old (452 ± 174 s) adults. The reduction in maximal voluntary contraction torque (%initial) for the wrist flexors after the fatiguing contraction was greater (P = 0.006) for young (32.5 ± 13.7%) than old (21.8 ± 6.6%) adults. Moreover, maximal voluntary contraction torque for the wrist extensors declined for old (–13.7 ± 12.7%; P = 0.030), but not young (–5.4 ± 13.8%; P = 0.167), adults. Torque steadiness during the matching task with the wrist extensors was similar before and after the fatiguing contraction for both groups, but the level of coactivation increased after the fatiguing contraction for old (P = 0.049) but not young (P = 0.137) adults and was twice the amplitude for old adults (P = 0.002). These data reveal that old adults are able to adjust the amount of antagonist muscle activity independent of the agonist muscle during steady submaximal contractions.

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A low-cost system to easily measure spontaneous physical activity in rodents

Spontaneous physical activity (SPA) can be responsible for variations of a lot of physiological parameters at the molecular, cellular, tissue, and systemic levels. It is increasingly recognized that good understanding of a large part of experimental results requires weighting them by SPA in order to reduce variability and thus to decrease the number of animals necessary to conduct a study. However, because of the high cost of this equipment, only a few laboratories are equipped with such equipment to measure the SPA of their animals. Here we present an effective, adaptable, and affordable system to measure SPA in rodents based on video acquisition of the animal in its own environment. We compared results obtained with our system to those collected at the same time with a commercial system of actimetry recording, and we found a high degree of correlation between these two approaches (r = 0.93; P < 0.001). We also were able to detect small variations of SPA induced by a special environment like chronic hypoxia exposure (25% less spontaneous activity compared with animals in normoxia, P < 0.05) or during the circadian cycle (107% more activity during the nocturnal phase compared with the diurnal phase, P < 0.05).

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Erratum to: Diagnostic value of cone-beam CT in histologically confirmed otosclerosis.

Erratum to: Diagnostic value of cone-beam CT in histologically confirmed otosclerosis.

Eur Arch Otorhinolaryngol. 2016 Apr 29;

Authors: Liktor B, Révész P, Csomor P, Gerlinger I, Sziklai I, Karosi T

PMID: 27130206 [PubMed - as supplied by publisher]

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The evaluation of cochlear functions in Familial Mediterranean Fever.

The evaluation of cochlear functions in Familial Mediterranean Fever.

Eur Arch Otorhinolaryngol. 2016 Apr 29;

Authors: Eryilmaz MA, Yucel A, Cure E, Sakiz D, Koder A, Kucuk A, Tunc R

Abstract
Familial Mediterranean Fever (FMF) is a progressive disease characterized by chronic inflammation, which also has negative effects on cochlear functions and hearing levels. We investigated whether the cochlear functions and hearing levels of FMF patients were different than healthy controls and also evaluated the relationship of hearing levels with the age at diagnosis, duration without treatment, and inflammation and lipid parameters in this study. A total of 60 patients diagnosed with FMF and 48 age, gender and body mass index (BMI)-matched healthy controls were included in the study. The hemogram, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lipid parameters of the subjects were studied and they all underwent pure tone audiometry and Transient evoked otoacoustic emission tests after an otologic examination. The hearing levels of the FMF group were significantly higher than those of the control group. The TEOAE signal/noise (S/N) ratios were similar in both groups. A positive relationship was present between the audiometric test results and the age, BMI, low-density lipoprotein and triglyceride levels and a negative relationship with the high-density lipoprotein levels. A negative relationship was present between the TEOAE S/N ratios and the age of the patients, duration without treatment, lipid parameters, inflammation markers and the creatinine level. FMF patients are exposed to chronic inflammation and this can influence their hearing levels. The age at diagnosis, duration without treatment, chronic inflammation, unfavorable lipid parameters, and obesity can affect hearing tests negatively.

PMID: 27130205 [PubMed - as supplied by publisher]

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Tryptophan and tryptophan-like substances in cloud water: Occurrence and photochemical fate

Publication date: July 2016
Source:Atmospheric Environment, Volume 137
Author(s): Angelica Bianco, Monica Passananti, Laurent Deguillaume, Gilles Mailhot, Marcello Brigante
This work investigates the occurrence and photochemical behaviour of tryptophan (TRP) in the cloud aqueous phase. The concentrations of tryptophan, TRYptophan LIke Substances (TRYLIS) and HUmic LIke Substances (HULIS) in real cloud water, collected between October 2013 and November 2014 at the top of the puy de Dôme station, were determined using the Excitation-Emission-Matrix (EEM) technique. The amount of free and complexed tryptophan (TRP) up to 10⁻⁷ M in cloud aqueous phase was quantified by HPLC-UV-fluorescence analysis, and its photoreactivity under sun-simulated conditions was investigated in synthetic water samples mimicking cloud aqueous phase compositions (oceanic and continental origins). TRP undergoes direct photolysis, and its degradation is enhanced in the presence of naturally occurring species able to photo-generate hydroxyl radicals (HO). The polychromatic quantum yield of TRP (ϕ290−340nmTRP) is estimated to be 8.37 × 10⁻⁴ between 290 and 340 nm, corresponding to the degradation rate (RTRPd) of 1.29 × 10⁻¹¹ M s⁻¹ under our irradiation conditions. The degradation is accelerated up to 3.65 × 10⁻¹⁰ and 8.26 × 10⁻¹⁰ M s⁻¹ in synthetic oceanic and continental cloud water samples doped with 100 μM hydrogen peroxide, respectively.Hydroxyl radical-mediated transformation leads to the generation of different functionalized and oxidized products, as well as small carboxylic acids, such as formate and acetate. Moreover, fluorescent signals of irradiated solutions indicate the formation of HULIS.

Graphical abstract

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Ambient exposure to coarse and fine particle emissions from building demolition

Publication date: July 2016
Source:Atmospheric Environment, Volume 137
Author(s): Farhad Azarmi, Prashant Kumar
Demolition of buildings produce large quantities of particulate matter (PM) that could be inhaled by on-site workers and people living in the neighbourhood, but studies assessing ambient exposure at the real-world demolition sites are limited. We measured concentrations of PM10 (≤10 μm), PM2.5 (≤2.5 μm) and PM1 (≤1 μm) along with local meteorology for 54 working hours over the demolition period. The measurements were carried out at (i) a fixed-site in the downwind of demolished building, (ii) around the site during demolition operation through mobile monitoring, (iii) different distances away from the demolition site through sequential monitoring, and (iv) inside an excavator vehicle cabin and on-site temporary office for engineers. Position of the PM instrument was continuously recorded using a Global Positioning System on a second basis during mobile measurements. Fraction of coarse particles (PM2.5–10) contributed 89 (with mean particle mass concentration, PMC ≈ 133 ± 17 μg m⁻³), 83 (100 ± 29 μg m⁻³), and 70% (59 ± 12 μg m⁻³) of total PMC during the fixed-site, mobile monitoring and sequential measurements, respectively, compared with only 50% (mean 12 ± 6 μg m⁻³) during the background measurements. The corresponding values for fine particles (PM2.5) were 11, 17 and 30% compared with 50% during background, showing a much greater release of coarse particles during demolition. The openair package in R and map source software (ArcGIS) were used to assess spatial variation of PMCs in downwind and upwind of the demolition site. A modified box model was developed to determine the emission factors, which were 210, 73 and 24 μg m⁻² s⁻¹ for PM10, PM2.5 and PM1, respectively. The average respiratory deposited doses to coarse (and fine) particles inside the excavator cabin and on-site temporary office increased by 57- (and 5-) and 13- (and 2-) times compared with the local background level, respectively. The monitoring stations in downwind direction illustrated a logarithmic decrease of PM with distance. Energy-dispersive X-ray spectroscopy and scanning electron microscopy were used to assess physicochemical features of particles. The minerals such as silica were found as a marker of demolition dust and elements such as sulphur coming from construction machinery emissions. Findings of this study highlight a need to limit occupational exposure of individuals to coarse and fine particles by enforcing effective engineering controls.

Graphical abstract

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Reduced-form modeling of public health impacts of inorganic PM2.5 and precursor emissions

Publication date: July 2016
Source:Atmospheric Environment, Volume 137
Author(s): Jinhyok Heo, Peter J. Adams, H. Oliver Gao
It is challenging to estimate the public health costs of fine particulate matter (PM2.5) and its precursor emissions accurately and quickly for policy research because of their complex physical and chemical processes occurring over a large downwind area. We developed a method for building statistical regressions that estimate public health cost of emissions accurately like a state-of-the-art chemical transport model (CTM) but without its high computational cost. This method achieves detailed spatial resolution according to the location of the emission source, accounting for differences in the exposed population downwind. Using tagged CTM simulations, our method builds a large dataset of air quality public health costs from marginal emissions throughout the United States. Two methods were developed to describe exposed population, one that assumes a generic downwind plume concentration profile derived from CTM outputs and a simpler method that uses the size of population within certain distances as variables. Using the former method, we parameterized marginal public health cost [$/t] and intake fraction [ppm] as a function of exposed population and key atmospheric variables. We derived models for elemental carbon, sulfur dioxide, nitrogen oxides, and ammonia. Compared to estimates calculated directly using CTM outputs, our models generally show mean fractional errors of only 10%–30% and up to 50% for NOx in some seasons, which are generally similar to or less than CTM's performance. Our results show that the public health costs of emissions can be efficiently parameterized for policy analyses based on state-of-the-art CTMs.

Graphical abstract

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Episodic air quality impacts of plug-in electric vehicles

Publication date: July 2016
Source:Atmospheric Environment, Volume 137
Author(s): Ghazal Razeghi, Marc Carreras-Sospedra, Tim Brown, Jack Brouwer, Donald Dabdub, Scott Samuelsen
In this paper, the Spatially and Temporally Resolved Energy and Environment Tool (STREET) is used in conjunction with University of California Irvine – California Institute of Technology (UCI-CIT) atmospheric chemistry and transport model to assess the impact of deploying plug-in electric vehicles and integrating wind energy into the electricity grid on urban air quality. STREET is used to generate emissions profiles associated with transportation and power generation sectors for different future cases. These profiles are then used as inputs to UCI-CIT to assess the impact of each case on urban air quality.The results show an overall improvement in 8-h averaged ozone and 24-h averaged particulate matter concentrations in the South Coast Air Basin (SoCAB) with localized increases in some cases. The most significant reductions occur northeast of the region where baseline concentrations are highest (up to 6 ppb decrease in 8-h-averaged ozone and 6 μg/m³ decrease in 24-h-averaged PM2.5). The results also indicate that, without integration of wind energy into the electricity grid, the temporal vehicle charging profile has very little to no effect on urban air quality. With the addition of wind energy to the grid mix, improvement in air quality is observed while charging at off-peak hours compared to the business as usual scenario.

Graphical abstract

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A new reconstruction of atmospheric gaseous elemental mercury trend over the last 60 years from Greenland firn records

Publication date: July 2016
Source:Atmospheric Environment, Volume 136
Author(s): A. Dommergue, P. Martinerie, J. Courteaud, E. Witrant, D.M. Etheridge
This study presents measurements of gaseous elemental mercury (GEM) concentrations in the 80 m of firn air at the international drilling site of NEEM in Greenland (2452 m, 77°25.8 N, 51°06.4 W). Using inverse modeling, we were able to reconstruct the atmospheric GEM trend at this Arctic site over the last 60 years. We show discrepancies between this record and the previous firn record of Summit. This could be attributed to experimental biases and/or differences in air mass transport. A multisite inverse model was used to derive an atmospheric scenario reconciling the two firn records. We show that GEM seasonal variations are very limited at these high altitude sites and thus probably unaffected by spring/summer photochemistry. The firn reconstructions suggest an increase of GEM concentrations since the 1950s peaking in the late 1960s and early 1970s. A decrease is then observed with minimum GEM concentrations around 1995–2000. The reconstruction compares well with historical mercury (Hg) releases and recent simulations of atmospheric Hg. Our optimal GEM scenario does not allow to categorically conclude on recent trends for GEM concentrations over the 2000–2010 decade.



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Targeted silencing of survivin in cancer cells by siRNA loaded chitosan magnetic nanoparticles.

Targeted silencing of survivin in cancer cells by siRNA loaded chitosan magnetic nanoparticles.

Expert Rev Anticancer Ther. 2016 Apr 29;

Authors: Unsoy G, Gunduz U

Abstract
OBJECTIVE: The aim of this study was to silence Survivin expression, related with drug-resistance, via siRNA-loaded CS-MNPs.
METHODS AND RESULTS: The highest siRNA-loading efficiency was achieved at siRNA:CS-MNP ratio of 1:2. Nanoparticles had spherical morphology and homogenous size distribution in TEM. After siRNA loading, core sizes (3-5nm) of CS-MNPs didn't change significantly, however hydrodynamic diameters increased ~10nm, indicating swelling of chitosan coat due to efficient siRNA loading. 73% of siRNA was pH-dependently released at 24hrs, after 30% burst release at first 3.5hrs. Stability was high enough to keep siRNAs in CS-MNPs at pH7.2. Cellular-internalization of Survivin-siRNA-CS-MNPs was high and localized in cytoplasm of cells.
CONCLUSION: Although, mock-siRNA loaded/unloaded CS-MNPs weren't cytotoxic, cell-death of breast cancer cells was significantly increased, after the treatment of Survivin-siRNA-loaded CS-MNPs. This reveals, successful loading of Survivin-siRNA on CS-MNPs and significant silencing of Survivin expression by triggering cell-death. Consequently, CS-MNPs are highly efficient delivery systems for intact siRNAs.

PMID: 27130312 [PubMed - as supplied by publisher]

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Role of Vitamin K Antagonists in the Prevention of Thrombotic Bypass Occlusion After Infrainguinal Venous Bypass

Publication date: Available online 30 April 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): E. Gándara, D. Hammond, S. Nagpal
Clinical vignetteDespite being the most common antithrombotic strategy in trials comparing venous with prosthetic grafts, the use of vitamin K antagonists (VKAs) to improve the outcome of venous bypass remains the subject of debate. In this systematic review, evidence supporting the use of VKAs for improving venous patency following infrainguinal venous bypass is provided.Clinical questionA 67 year old man with lifestyle limiting claudication underwent a successful infrainguinal venous bypass. Can VKAs help preserve patency after venous bypass surgery?MethodsA systematic review of electronic databases, including MEDLINE and Embase, was conducted. Only randomized controlled studies comparing VKAs with aspirin (ASA) were included. The main outcome was bypass patency.ResultsFour studies using different intensities of anticoagulation ± ASA were identified. All but one showed a benefit of VKAs over ASA with respect to primary patency. However, this benefit was also accompanied by an increased risk of bleeding. The Dutch Bypass Oral Anticoagulants, or ASA, study was the largest included and showed that VKAs (without concomitant ASA) were superior to ASA alone for the prevention of graft occlusion (hazard ratio 0.69, 95% confidence interval 0.54–0.88).ConclusionCurrent evidence suggests that VKAs are superior to ASA for the prevention of infrainguinal autologous venous graft thrombosis.



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Self-referral to the NHS Abdominal Aortic Aneurysm Screening Programme

Publication date: Available online 30 April 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): L. Meecham, J. Jacomelli, A.D. Pherwani, J. Earnshaw
IntroductionThe NHS Abdominal Aortic Screening Programme (NAAASP) invites men in their 65th year for screening, men over 65 may self-refer into the programme. Most studies have concentrated on those invited for screening, little is known about the self-referral group. Our aim was to provide a descriptive analysis of the men who self refer to NAAASP for screening.MethodInformation concerning basic demographic details and ultrasound results were recorded on the AAA SMaRT database. During nurse assessment data collected included smoking status, blood pressure, height, weight, and aspirin and statin therapy. Statistical analysis was performed using SPSS^®20.ResultsA total of 58,999 men have self-referred to the NAAASP since its inception. The mean age at self-referral was 73 (47–100). The mean aortic diameter was 1.9 cm (0.8–12.1). Increased self-referral rates were observed following organised publicity. The incidence of AAA was 4.1% (n = 2438) compared with 1.4% in the invited cohort (age 65 years), of these 7.6% (n = 186) were >5.5 cm. Of the 186, 152 (81.7%) underwent surgery, of which 55.3% (n = 84) underwent EVAR. The 30-day mortality in the men treated electively was 0%. The mean time from referral to surgery was 69 (2–361) days, with 57.9% (n = 88) being treated within 8 weeks of detection.ConclusionSelf-referral has yielded higher detection rates than the invited cohort, more than justifying its cost. Now that NAAASP is fully operational it is important to continue media campaigns and publicity to target the "at-risk" men over 65 who would otherwise miss the benefits of AAA screening. Some key areas still need to be addressed.



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Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-κB-dependent manner.

Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-κB-dependent manner.

Biochem Biophys Res Commun. 2016 Apr 26;

Authors: Fitzpatrick SF, Fábián Z, Schaible B, Lenihan CR, Schwarzl T, Rodriguez J, Zheng X, Li Z, Tambuwala MM, Higgins DG, O'Meara Y, Slattery C, Manresa MC, Fraisl P, Bruning U, Baes M, Carmeliet P, Doherty G, von Kriegsheim A, Cummins EP, Taylor CT

Abstract
Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1 confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) and nuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, we investigated the underlying mechanism(s) in hepatocytes. Basal NF-κB activity was elevated in PHD1(-/-) hepatocytes compared to wild type controls. ChIP-seq analysis confirmed enhanced binding of NF-κB to chromatin in regions proximal to the promoters of genes involved in the regulation of apoptosis. Inhibition of NF-κB (but not knock-out of HIF-1 or HIF-2) reversed the anti-apoptotic effects of pharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to altered expression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides new information relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that has been reported in pre-clinical models of intestinal and hepatic disease.

PMID: 27130823 [PubMed - as supplied by publisher]

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The relationship between cortical auditory evoked potentials (CAEPs) and speech perception in children with Nurotron® cochlear implants during four years of follow-up

Publication date: June 2016
Source:International Journal of Pediatric Otorhinolaryngology, Volume 85
Author(s): Qianqian Guo, Yuling Li, Xinxing Fu, Hui Liu, Jing Chen, Chao Meng, Mo Long, Xueqing Chen
ObjectiveThe purpose of the current study was to evaluate the relationship between the presence or absence of cortical auditory evoked potentials (CAEPs) to speech stimuli and the performance of speech perception in Chinese pediatric recipients of the Nurotron^® cochlear implant (CI).We also wanted to determine how the CAEPs might be used as an indicator for predicting early speech perception and could provide objective evidence for clinical applications of CAEPs.Methods23 pediatric unilateral CI recipients participated in this study. 15 males 8 females, and their ages at implantation ranged from 13 to 68 months, with a mean age of 36 months. CAEPs and Mandarin Early Speech Perception (MESP) tests were used to evaluate the audibility and speech perception of these CI users. The tests were administered at the first, second, third, and fourth year after the CI surgery.ResultsAll the subjects demonstrated improvements in detection of speech sounds with CI. The percentages of participants who could detect all three stimuli were 26% (6/23) at first year, to 100% (23/23) at the fourth year post-implantation. The percentages of participants who passed the Category 6 of MESP were from 9% (2/23) at first year, to 91% (21/23) at the fourth year post-implantation. Significant correlations (p<0.05) were found between CAEP scores and MESP at the first, second, third year after the CI surgery. The multiple regression equation for prediction of MESP categories from CAEP scores and hearing ages was MESP=1.088+(0.504×CAEP score)+(0.964×hearing ages) (F=72.919, p<0.001, R²=0.621).ConclusionThe results of this study suggested that aided cortical assessment was a useful tool to evaluate the outcomes of cochlear implantation. Cortical outcomes had a significant positive relationship with the MESP, which predicted the early speech perception of CI recipients.



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Pediatric laryngotracheal separation following a go-cart injury

Publication date: June 2016
Source:International Journal of Pediatric Otorhinolaryngology, Volume 85
Author(s): Polpatt Jitpakdee, Toby Steele, Aditi Bhuskute, Dhave Setabutr
Less than one percent of trauma admission cases are categorized as pediatric neck trauma [13]. Nevertheless, due to an increasingly mobile society, there has been an increasing frequency of pediatric neck trauma with motor vehicle accidents being the most common mechanism of injury [8].We present a case of laryngotracheal separation from a blunt, clothesline injury to the neck in a pediatric patient. We also review the literature and discuss the benefit of balloon airway dilation and its assistance in the management of laryngeal trauma and its resultant effects.



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Protective role of garlic oil against oxidative damage induced by furan exposure from weaning through adulthood in adult rat testis.

Protective role of garlic oil against oxidative damage induced by furan exposure from weaning through adulthood in adult rat testis.

Acta Histochem. 2016 Apr 26;

Authors: El-Akabawy G, El-Sherif NM

Abstract
Furan is produced in a wide variety of heat-treated foods via thermal degradation. Furan contamination is found to be relatively high in processed baby foods, cereal products, fruits juices, and canned vegetables. Several studies have demonstrated that furan is a potent hepatotoxin and hepatocarcinogen in rodents. However, few studies have investigated the toxic effects of furan in the testis. In addition, the exact mechanism(s) by which furan exerts toxicity in the testis has not been fully elucidated. In this study, we investigated the potential of furan exposure from weaning through adulthood to induce oxidative stress in adult rat testis, as well as the potential of garlic oil (GO) to ameliorate the induced toxicity. Our results reveal that furan administration significantly reduced serum testosterone levels and increased the levels of malondialdehyde (MDA); furthermore, furan administration decreased significantly the enzymatic activity of testicular antioxidants, including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) and induced histopathological alterations in the testis. GO co-administration ameliorated the reduction in testosterone levels and dramatically attenuated the furan-induced oxidative and histopathological changes. In addition, Go significantly down-regulated the increased caspase-3 and cytochrome P450 2E1 (CYP2E1) expression in the furan-treated testis. To the best of our knowledge, this study is the first to demonstrate the furan-induced oxidative changes in the adult rat testis and the protective role of GO to ameliorate these changes through its antioxidant effects and its ability to inhibit CYP2E1 production.

PMID: 27130490 [PubMed - as supplied by publisher]

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Digital image analysis of ossification centers in the axial dens and body in the human fetus.

Digital image analysis of ossification centers in the axial dens and body in the human fetus.

Surg Radiol Anat. 2016 Apr 29;

Authors: Baumgart M, Wiśniewski M, Grzonkowska M, Małkowski B, Badura M, Dąbrowska M, Szpinda M

Abstract
PURPOSES: The detailed understanding of the anatomy and timing of ossification centers is indispensable in both determining the fetal stage and maturity and for detecting congenital disorders. This study was performed to quantitatively examine the odontoid and body ossification centers in the axis with respect to their linear, planar and volumetric parameters.
METHODS: Using the methods of CT, digital image analysis and statistics, the size of the odontoid and body ossification centers in the axis in 55 spontaneously aborted human fetuses aged 17-30 weeks was studied.
RESULTS: With no sex difference, the best fit growth dynamics for odontoid and body ossification centers of the axis were, respectively, as follows: for transverse diameter y = -10.752 + 4.276 × ln(age) ± 0.335 and y = -10.578 + 4.265 × ln(age) ± 0.338, for sagittal diameter y = -4.329 + 2.010 × ln(age) ± 0.182 and y = -3.934 + 1.930 × ln(age) ± 0.182, for cross-sectional area y = -7.102 + 0.520 × age ± 0.724 and y = -7.002 + 0.521 × age ± 0.726, and for volume y = -37.021 + 14.014 × ln(age) ± 1.091 and y = -37.425 + 14.197 × ln(age) ± 1.109.
CONCLUSIONS: With no sex differences, the odontoid and body ossification centers of the axis grow logarithmically in transverse and sagittal diameters, and in volume, while proportionately in cross-sectional area. Our specific-age reference data for the odontoid and body ossification centers of the axis may be relevant for determining the fetal stage and maturity and for in utero three-dimensional sonographic detecting segmentation anomalies of the axis.

PMID: 27130209 [PubMed - as supplied by publisher]

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