“Pseudoprogression”: more than semantics

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Contact-independent suppressive activity of regulatory T cells is associated with telomerase inhibition, telomere shortening and target lymphocyte apoptosis

Publication date: September 2018

Source: Molecular Immunology, Volume 101

Author(s): Dmitry D. Zhdanov, Yulia A. Gladilina, Dmitry V. Grishin, Vladimir A. Grachev, Valentina S. Orlova, Marina V. Pokrovskaya, Svetlana S. Alexandrova, Vadim S. Pokrovsky, Nikolai N. Sokolov

Abstract

Regulatory T cells (Tregs) play a fundamental role in the maintenance of immunological tolerance by suppressing effector target T, B and NK lymphocytes. Contact-dependent suppression mechanisms have been well–studied, though contact-independent Treg activity is not fully understood. In the present study, we showed that human native Tregs, as well as induced ex vivo Tregs, can cause in vitro telomere-dependent senescence in target T, B and NK cells in a contact-independent manner. The co-cultivation of target cells with Tregs separated through porous membranes induced alternative splicing of the telomerase catalytic subunit hTERT (human Telomerase Reverse Transcriptase), which suppressed telomerase activity. Induction of the hTERT splicing variant was associated with increased expression of the apoptotic endonuclease EndoG, a splicing regulator. Inhibited telomerase in target cells co-cultivated with Tregs for a long period of time led to a decrease in their telomere lengths, cell cycle arrest, conversion of the target cells to replicative senescence and apoptotic death. Induced Tregs showed the ability to up-regulate EndoG expression, TERT alternative splicing and telomerase inhibition in mouse T, B and NK cells after in vivo administration. The results of the present study describe a novel mechanism of contact-independent Treg cell suppression that induces telomerase inhibition through the EndoG-provoked alternative splicing of hTERT and converts cells to senescence and apoptosis phenotypes.

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The comparison of single-dose preemptive intravenous ibuprofen and paracetamol on postoperative pain scores and opioid consumption after open septorhinoplasty: a randomized controlled study

Abstract

Purpose

Septorhinoplasty is performed in combination with septoplasty and rhinoplasty operations and is characterized by severe postoperative pain. The aim of this study is to evaluate preemptive effects of intravenous (IV) ibuprofen and IV paracetamol on opioid consumption and pain scores after open septorhinoplasty.

Methods

The study included 150 patients who had undergone elective open septorhinoplasty. Patients were randomly assigned into three groups; Group Control (Group C, n = 50) received 100 ml saline solution, Group Paracetamol (Group P, n = 50) received 1000 mg IV paracetamol in 100 ml solution, and Group Ibuprofen (Group I, n = 50) received 800 mg IV ibuprofen in 100 ml saline before surgery. Postoperative analgesia was achieved by opioid administration via patient-controlled analgesia. Visual analog scores (VASs), postoperative opioid consumption, additional analgesic requirements, and side effects were recorded.

Results

Compared with Group C, VASs in Group P and Group I were statistically lower at all time points (p < 0.05). VAS was lower in Group I than in Group P at postoperative, 1st and 6th hours (p < 0.05). Opioid consumption in Group C was highest in all groups at all time periods (p < 0.05). At the 0–6 and 6–12 time intervals, total opioid consumption was significantly lower in Group I compared to Group P (p < 0.05). Total opioid consumption was highest in Group C (p < 0.05).

Conclusions

This study has indicated that ibuprofen has more analgesic effect than paracetamol during first 12 h, but there is a non-inferiority between ibuprofen and paracetamol after first 12 h.

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Hepatozelluläres Karzinom – Stellenwert von Resektion, Lebertransplantation und Immunsuppression

Zusammenfassung

Das hepatozelluläre Karzinom (HCC) kann im Stadium BCLC 0 und A (Barcelona Classification of Liver Cancer) sowohl mittels Resektion als auch mittels Lebertransplantation innerhalb der Mailand-Kriterien erfolgreich kurativ behandelt werden. Bei Patienten ohne Zirrhose sollte immer eine Resektion angestrebt werden. Problematisch bei der Beurteilung der Therapie mittels Resektion und Lebertransplantation ist die Vergleichbarkeit. Die Berücksichtigung der portalen Hypertension zur Indikationsstellung muss in der Risiko-Nutzen-Bewertung für die Resektion streng beachtet werden. Multiple Analysen zeigen, dass beide Verfahren zu ähnlichen Ergebnissen führen. Der Überlebensvorteil für die Transplantation ist allerdings erst nach 10 Jahren erreicht. Die Implementation der Werte für AFP (α-Fetoprotein) hilft bei der Risikoabschätzung. Bezüglich der immunsuppressiven Therapie scheint eine niedrig dosierte Langzeitimmunsuppression und die Gabe eines mTOR-Inhibitors (mTORi) positive Effekte auf das Langzeitüberleben zu haben.

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Retrieval of weak x-ray scattering using edge illumination

Munro, PRT; Maughan Jones, C; (2018) Retrieval of weak x-ray scattering using edge illumination. Optics Letters (In press).

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Beware Occam’s Syntactic Razor: Morphotactic Analysis and Spanish Mesoclisis

Arregi, K; Nevins, A; (2018) Beware Occam's Syntactic Razor: Morphotactic Analysis and Spanish Mesoclisis. Linguistic Inquiry , 49 (4) 10.1162/ling_a_00286 . (In press). Green open access

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Isolated insulin-derived amyloidoma of the breast

Mayhew, JM; Alan, T; Kalidindi, V; Gandamihardja, TAK; (2017) Isolated insulin-derived amyloidoma of the breast. BMJ Case Reports , 2017 10.1136/bcr-2017-219491 . Green open access

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