The Radiosensitivity of Germ-cells at Various Stages of Ovarian Development

Summary

Female rats were exposed to 50 and 100 r x-rays on the 8th, 10th and 12th days of intra-uterine life, at birth and on the 2nd and 5th days after birth.

As judged by the survival of oocytes at the age of 25 days, germ-cells in the developing ovary undergo two periods of high radiosensitivity: the first at 15 days post coitum, when oogonial mitoses are frequent, and the second shortly after birth, when the oocytes attain the dictyate phase. The intervening period of relative refractoriness to radiation damage occurs while the oocytes undergo the prophase of meiosis.     

Pharmacokinetics and metabolism of a selective PDE5 inhibitor (UK-343,664) in rat and dog

1. UK-343,664 is a novel potent and selective PDE5 inhibitor. Plasma clearances in the male and female rat were high (120 and 54 ml min^-1 kg^-1), giving rise to short elimination half-lives (0.2 and 0.3?h respectively). Lower clearance in dog (14 mlmin^-1 kg^-1) was the primary factor resulting in a longer elimination half-life (3.7?h). The higher clearance in rat than dog was in agreement with in vitro metabolism rates in hepatic microsomes. 2. The volume of distribution was lower in rat (1.3-2.1 lkg^-1) compared with dog (4.6?l kg^-1     

Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington’s Disease

Using an iterative structure–activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, 12) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound 12 exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound 12 in mice to estimate a class I/IIb deacetylation EC₅₀, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. We observed excellent correlation between the compound 12 in vivo pharmacodynamic response and in vitro class I/IIb cellular activity. Applying the same relationship to class IIa HDAC inhibition, we estimated the compound 12 dose required to inhibit class IIa HDAC activity, for use in preclinical models of Huntington’s disease.     

Place du kinésithérapeute dans le traitement de la dyspnée

Dyspnoea is the most frequent complaint in respiratory diseases. During clinical care, the physiotherapist is often in front of a dyspneic patient.So the physiotherapist has an important place in care of the dyspneic patients, first time for the evaluation, and then for the treatment. He is also a major interlocutor in a multidisciplinary staff.This article aims to show evaluation tools of the dyspnoea which allow to cover the various domains of the dyspnoea, and then the different physiotherapy’s methods which allow to decrease it.     

Timing of dental extractions in patients undergoing radiotherapy and the incidence of osteoradionecrosis: a systematic review and meta-analysis

This systematic review aimed to examine whether the incidence of osteonecrosis differed between patients who have dental extractions before or after radiotherapy (RT). The reported incidence of osteoradionecrosis (ORN) of the jaws following RT to the head and neck varies widely in the literature. Currently, for patients with head and neck cancer there are no universally accepted guidelines on the optimal timing of dental surgery relative to RT to minimise incident ORN. A literature review was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria. A search of PubMed, EMBASE, Evidence-Based Medicine, and Web of Science databases targeted literature published up to and including 10 April 2020. Two independent reviewers assessed studies for eligibility against inclusion criteria. An assessment of bias was conducted for each of the included studies and relevant data extracted. A meta-analysis was undertaken using the statistical methods described. Twenty-four of 708 studies were included. They were heterogeneous and included a wide variation of RT methods, head and neck malignancies, and comorbidities. While some concluded that the incidence of ORN was dependent on the timing of dental extractions in relation to RT, with regard to the risk of its development, others reported additional factors such as age, comorbidities, extent of surgical resection, and dose and field of radiation, as more important predictors than timing. In many there was consistent lack of detail around the timing of dental procedures in relation to the delivery of RT. From 21 studies including 36,294 patients, of whom 14,389 had extractions before RT, the pooled incidence of ORN was 5.5% (95% CI: 2.1% to 10.1%). Significant heterogeneity was found in Cochran’s Q-test (p < 0.001) and Higgins I² = 98.0%. From 21 studies including 37,805 patients, of whom 6030 had extractions after RT, the pooled incidence of ORN was 5.3% (95% CI: 2.9% to 8.2%). Significant heterogeneity was found in Cochran’s Q-test (p < 0.001) and Higgins I² = 80.0%. There was no statistically significant difference between these two groups (random-effects model Q=0.12, p=0.73). Large, longitudinal studies with a priori-specified methods are needed to identify, recruit, and prospectively follow patients with head and neck cancer for the onset of ORN after dental surgery. This will allow clinical guidelines to be established to assist clinicians to plan treatment when extractions are indicated in patients undergoing RT to the head and neck.