Histological Observation of the Development of Follicles and Follicular Atresia in Immature Rat Ovaries

To clarify the development of follicular growth and atresia in the immature ovary, rats. ovaries and blood were removed at fixed points during the period from 0 to 35 days after birth (Day 0 to Day 35). The ovaries were immunohistochemically examined, and blood concentrations of serum follicle-stimulating hormone (FSH) and estrogen (E) were measured. We investigated how time-course changes in follicular cell proliferation, estrogen receptor β (ERβ), apoptosis, and FSH and E concentrations are connected with follicular growth and atresia. Apoptosis was found in the ova from Day 0 to Day 3. On Day 15, apoptosis occurred in some granulosa cell nuclei in some follicles, but BrdU uptake and the presence of cyclin D2 and ER β could be observed in other granulosa cells. From Day 17, apoptosis increased in the follicular granulosa cells, and BrdU uptake and the presence of cyclin D2 and ERβ were decreased. Follicular atresia continued, reaching a peak on Day 30. Serum FSH and E concentrations increased until Day 15, then markedly decreased after Day 17. The mechanism of apoptosis in the ova from Day 0 to 3 has not been clarified. However, the onset of follicular atresia was caused by apoptotic degeneration from Days 15 to 17. These results showed that the oocytes were selected by apoptosis at 2 points in the time-course of the maturation of the ovary

Differential, histochemical and immunohistochemical changes in rat hepatocytes after isoflurane or sevoflurane exposure.

Differential, histochemical and immunohistochemical changes were observed in hepatocytes from immediately to 7 days after isoflurane or sevoflurane exposure (at H 0 to on Day 7) to study the process of development and recovery in anesthetic-induced hepatic injury. A total of 570 7-week-old male Sprague-Dawley rats with or without phenobarbital treatment were exposed to isoflurane or sevoflurane in 100%, 21%, or 10% oxygen, or to 10% oxygen alone for 2h. In phenobarbital-treated rats, hepatocytes both with and without anesthetic exposure markedly changed in 10% oxygen at H 0. Glycogen and ribosomal ribonucleic acid (rRNA) disappeared at H 0 and at H 6, respectively, and at H 6, AST levels in the blood rose. From H 6 to Day 1, necrosis developed more markedly and widely in zone 3 hepatocytes exposed to anesthetics in 10% oxygen than in those exposed to oxygen alone. All degenerated tissues had returned to normal levels by day 7. Recovery of the hepatolobular structure may be attributed to rearrangement of remaining hepatocytes in the portal vein area. Both the disappearance of glycogen and rRNA and the increase in blood AST levels after exposure to isoflurane or sevoflurane are considered to be factors contributing to the induction of necrosis around the central vein. The grade of isoflurane-induced hepatic injury was found to be significantly higher than that of sevoflurane.</p

Changes in Drug Utilization After Publication of Clinical Trials and Drug-Related Scandals in Japan: An Interrupted Time Series Analysis, 2005–2017

Background: Breaches of ethics undermine the practice of medicine. In Japan, two major scandals involving clinical research and drug marketing occurred after the publication of clinical trials. To study the effects of those scandals, we evaluated changes in the use of first-generation angiotensin II receptor blockers (ARBs) after publication of relevant clinical trials and also after the subsequent scandals. Methods: We conducted a quasi-experimental design of an interrupted time series analysis (ITSA) on nationwide monthly drug-market data covering 12 years (2005 to 2017) in Japan. The main outcome was the use of first-generation ARBs (valsartan, candesartan, and losartan). The two exposures were the publication of ARB-related clinical-trial results (October 2006) and subsequent ARB-related scandals involving research and marketing (February 2013). A generalized estimating equation model was fitted for ITSA with a log link, Poisson distribution, robust variance estimators, and seasonality adjustment. Results: The publication of clinical trials was associated with 12% increase in the use of first-generation ARBs in Japan, and the subsequent ARB-related scandals was associated with 19% decrease. The decrease in the use of first-generation ARBs after the scandals was greater than the increase in their use after the publication of clinical-trial results. The net effect of the two exposures was a 9% decrease in the use of first-generation ARBs. Conclusions: The scandals were associated with decrease in the use of first-generation ARBs, and that decrease was greater than the increase associated with the publication of “successful” clinical trials, making the net effect not zero but negative

Body mass index change and estimated glomerular filtration rate decline in a middle-aged population: health check-based cohort in Japan

Background: Obesity is a growing public health problem worldwide. We evaluated the mediators and association between changes in obesity metrics and renal outcomes in the general population. Methods: Using the Japanese nationwide health check-based cohort from April 2011 to March 2019, we selected individuals aged 40–74 years, with a baseline estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2, whose body mass index (BMI) change was assessed. The primary outcome was combined 30% decline in eGFR, eGFR 4%) mediated by three risk factors (blood pressure, haemoglobin A1c and total cholesterol), was 13.3%. Conclusion: In the middle-aged Japanese population, both, increase and decrease in BMI were associated with subsequent eGFR decline. Changes in risk factors mediated a small proportion of the association between BMI increase and eGFR decline. Our findings support the clinical significance of monitoring BMI as a renal risk factor

Learning Health System In A Senior Retirement Community: A Platform To Promote Implementation Research

Introduction: In an effort to develop a Learning Health System (LHS) for a healthy ageing society, this study launched an Internet of Things (IoT) platform in a senior residential community to continuously generate behavior logs. Methods: Considering that older adults experience difficulties in technology adaptation and declined information processing abilities, senior residents only needed to carry around a card sized beacon which was the tracking device. Participant recruitment took place in a continuing care retirement community. Individual feedback was obtained quarterly. Results: During the first 16 months, 111 residents, aged 67 to 97 years, joined the program, and nearly 90% of them were consistently monitored in their everyday lives. Participants’ average daily walking distance was slightly less than 1 km. The average time spent socializing was between 1 to 1.5 hours per day. Conclusion: The IoT platform offers the possibility of extending the target population and scope of data, as well as incorporating experimental study designs. It is expected that factors affecting older people’s everyday lives and their consequences on health outcomes are continuously studied, learned from and improved

Quantification of PERF 15 mRNA in Tissue Sections from Rat Testes

We previously conducted basic research to quantify in situ hybridization (ISH) signals in rat testes. In this experimental model, we selected ribosomal RNA (rRNA) as the hybridizable RNA in paraffin sections, since it allowed us to easily analyze ISH signals expressed with digoxygenin (DIG)-labeled probes quantitatively through “posterization” of the images. We applied this method to analyze the quantification of transcript, PERF 15 mRNA. PERF 15 is expressed specifically in the testes and localized in the rigid cytoskeletal structure of the sperm head, and has been considered to be involved in the apoptotic process of spermatogenic cells. Quantification of the signals may help to clarify the detailed function of PERF 15. We further analyzed the signals concomitant with a confocal laser scanning microscope. The peak of PERF 15 mRNA expression was found in diplotene spermatocytes, and the amount of PERF 15 mRNA was greatest in late pachytene and diplotene spermatocytes and early spermatids, followed by early pachytene spermatocytes, and then late spermatids. PERF 15 may be involved in the events leading to meiotic division, in which apoptosis is also involved. The present study may help to determine the concentration of mRNA in tissue sections

Geranylgeranylacetone Ameliorates Inflammatory Response to Lipopolysaccharide (LPS) in Murine Macrophages: Inhibition of LPS Binding to The Cell Surface

We investigated whether pretreatment with geranylgeranylacetone (GGA), a potent heat shock protein (HSP) inducer, could inhibit proinflammatory cytokine liberation and nitric oxide (NO) production in lipopolysaccharide (LPS)-treated murine macrophages. The levels of NO and tumor necrosis factor-α (TNF-α) released from murine macrophage RAW 264 cells were increased dose- and time-dependently following treatment with LPS (1 µg/ml). GGA (80 µM) treatment 2 h before LPS addition significantly suppressed TNF-α and NO productions at 12 h and 24 h after LPS, respectively, indicating that GGA inhibits activation of macrophages. However, replacement by fresh culture medium before LPS treatment abolished the inhibitory effect of GGA on NO production in LPS-treated cells. Furthermore, GGA inhibited both HSP70 and inducible NO synthase expressions induced by LPS treatment despite an HSP inducer. When it was examined whether GGA interacts with LPS and/or affects expression of Toll-like receptor 4 (TLR4) and CD14 on the cell surface, GGA inhibited the binding of LPS to the cell surface, while GGA did not affect TLR4 and CD14 expressions. These results indicate that GGA suppresses the binding of LPS to the cell surface of macrophages, resulting in inhibiting signal transduction downstream of TLR4

A novel method for assessing the renal biopsy specimens using an activatable fluorescent probe

Gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) is an activatable fluorescent probe that can be activated by γ-glutamyltranspeptidase (GGT). The expression of GGT in the kidney, which is one of the major organs exhibiting enhanced GGT expression, is exclusively localised to the cortex. Here, we aimed to investigate the feasibility of gGlu-HMRG as a probe for the on-site assessment of renal biopsy specimens. gGlu-HMRG fluorescent probe was applied to the renal proximal tubular epithelial cells and cortical collecting duct cells in vitro, mouse kidneys ex vivo, and human biopsy specimens. In addition, the fluorescence intensities in the cortex and the medulla were comparatively evaluated in the biopsy specimens. The fluorescence signal was rapidly detected in the renal proximal tubular epithelial cells, whereas that in the cortical collecting duct cells was not detected. The fluorescence signal was detected in the mouse kidneys ex vivo without markedly affecting the tissue morphology. In the human biopsy specimens, the fluorescence signal in the cortex was significantly distinct from that in the medulla (p?<?0.05). Thus, this fluorescent probe can be used to distinctly identify the renal cortex in the biopsy specimens