PTGER1 and PTGER2 receptors mediate regulation of progesterone synthesis and type 1 11β-hydroxysteroid dehydrogenase activity by prostaglandin E2 in human granulosa–lutein cells

In luteinizing granulosa cells, prostaglandin E2 (PGE2) can exert luteotrophic actions, apparently via the cAMP signalling pathway. In addition to stimulating progesterone synthesis, PGE2 can also stimulate oxidation of the physiological glucocorticoid, cortisol, to its inactive metabolite, cortisone, by the type 1 11β-hydroxysteroid dehydrogenase (11βHSD1) enzyme in human granulosa–lutein cells. Having previously shown these human ovarian cells to express functional G-protein coupled, E-series prostaglandin (PTGER)1, PTGER2 and PTGER4 receptors, the aim of this study was to delineate the roles of PTGER1 and PTGER2 receptors in mediating the effects of PGE2 on steroidogenesis and cortisol metabolism in human granulosa–lutein cells. PGE2-stimulated concentration-dependent increases in both progesterone production and cAMP accumulation (by 1·9±0·1- and 18·7±6·8-fold respectively at 3000 nM PGE2). While a selective PTGER1 antagonist, SC19220, could partially inhibit the steroidogenic response to PGE2 (by 55·9±4·1% at 1000 nM PGE2), co-treatment with AH6809, a mixed PTGER1/PTGER2 receptor antagonist, completely abolished the stimulation of progesterone synthesis at all tested concentrations of PGE2 and suppressed the stimulation of cAMP accumulation. Both PGE2 and butaprost (a preferential PTGER2 receptor agonist) stimulated concentration-dependent increases in cortisol oxidation by 11βHSD1 (by 42·5±3·1 and 40·0±3·0% respectively, at PGE2 and butaprost concentrations of 1000 nM). Co-treatment with SC19220 enhanced the ability of both PGE2 and butaprost to stimulate 11βHSD1 activity (by 30·2±0·2 and 30·5±0·6% respectively), whereas co-treatment with AH6809 completely abolished the 11βHSD1 responses to PGE2 and butaprost. These findings implicate the PTGER2 receptor–cAMP signalling pathway in the stimulation of progesterone production and 11βHSD1 activity by PGE2 in human granulosa–lutein cells

Groundwater quality and antibiotic resistance of coliform bacteria in Wilgamuwa, an area of Chronic Kidney Disease of unknown etiology (CKDu) in Sri Lanka

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Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by Transforming Growth Factor β and Angiotensin II.

BACKGROUND: Absorption of water and Na(+) in descending colonic crypts is dependent on the barrier function of the surrounding myofibroblastic pericryptal sheath. Here the effects of high and low Na(+) diets and exposure to whole body ionising radiation on the growth and activation of the descending colonic pericryptal myofibroblasts are evaluated. In addition the effect of a post-irradiation treatment with the angiotensin converting enzyme inhibitor Captopril was investigated. METHODS: The levels of Angiotensin II type 1 receptor (AT1), ACE, collagen type IV, transforming growth factor-β type 1 receptor (TGF-βR1), OB cadherin and α-smooth muscle actin in both descending colon and caecum were evaluated, using immunocytochemistry and confocal microscopy, in rats fed on high and low Na(+) diets (LS). These parameters were also determined during 3 months post-irradiation with 8Gy from a (60)Co source in the presence and absence of the angiotensin converting enzyme inhibitor, Captopril. RESULTS: Increases in AT1 receptor (135.6% ± 18.3, P < 0.001); ACE (70.1% ± 13.1, P < 0.001); collagen type IV (49.6% ± 15.3, P < 0.001); TGF-β1 receptors (291.0% ± 26.5, P < 0.001); OB-cadherin (26.3% ± 13.8, P < 0.05) and α-smooth muscle actin (82.5% ± 12.4, P < 0.001) were observed in the pericryptal myofibroblasts of the descending colon after LS diet. There are also increases in AT1 receptor and TGF-β1 receptor, smooth muscle actin and collagen type IV after irradiation. Captopril reduced all these effects of irradiation on the pericryptal sheath and also decreased the amount of collagen and smooth muscle actin in control rats (P < 0.001). CONCLUSIONS: These results demonstrate an activation of descending colonic myofibroblasts to trophic stimuli, or irradiation, which can be attenuated by Captopril, indicative of local trophic control by angiotensin II and TGF-β release

Documenting the Recovery of Vascular Services in European Centres Following the Initial COVID-19 Pandemic Peak: Results from a Multicentre Collaborative Study

Objective: To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak. Methods: An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March – May 2020, “period 1”), and then again between May and June (“period 2”) and June and July 2020 (“period 3”). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume. Results: The impact of the pandemic continued to be felt well after countries’ first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence. Conclusion: Centres reported a broad return of services approaching pre-pandemic “normal” by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries

The effect of <i>Piper</i> <i>betle</i> against <i>Candida</i> <i>albicans</i> adherence to denture acrylic surfaces

Antimicrobial activity of medicinal plants has been identified since ancient times, and has been used to cure bacterial and fungal diseases. Piper betle is an important medicinal plant with its medicinal properties extending to antimicrobial activity against several pathogenic fungi and bacteria. The objective of this study was to evaluate the effect of P. betle leaf extract on Candida albicans adhesion on denture acrylics. Young betel leaves (1st - 3rd leaf) were subjected to vacuum infiltration with ethanol. Anticandidal activity of a range of concentrations of the leaf extract (5,000 – 10,000 ppm) was assessed against C. albicans (ATCC 90028) and seven laboratory isolates using the agar well bioassay. Further, the same concentrations were used to test their ability to suppress the adhesion of C. albicans on denture acrylics, as compared to a commercial denture cleanser (positive control), and sterile distilled water (negative control) using an adhesion assay. The results indicated that sterile distilled water had the highest adhesion (23.75 ±5.3 cells per unit area) while both, the leaf extract of concentrations of 8,000 – 10,000 ppm and the commercial denture cleanser showed significant (p &lt; 0.05) suppression of C. albicans adhesion on denture acrylics. There was no significant difference between adhesion in an 8000 ppm concentration extract of P. betle and the commercial denture cleanser of equal concentration, indicating that betel leaf extract is as efficient as the commercial denture cleanser, in suppressing the adhesion of C. albicans on denture acrylic surface