Degeneration of retinal ganglioncells in hypoxic responses: hypoxia-inducible factor inhibition,a new therapeutic insight

Degeneration of retinal ganglion cells (RGCs) is one of the hallmarks of common optic neuropathies (Weinreb et al., 2014). Glaucoma, the most common optic neuro...     

Induction of immunoreactive proliferating cell nuclear antigen (PCNA) in goldfish retina following intravitreal injection with tunicamycin.

Effects of a photoreceptor-specific biotoxin, tunicamycin (TM), injected intravitreally into the goldfish eye at one side, were explored on electroretinograms (ERGs) and proliferating cell nuclear antigen-immunoreactive (PCNA-ir) nuclei, representing the mitotic activity of rod precursors, in the retina at both sides. The eye-cup preparations were made for ERG recording, and the retinas were isolated and processed as cryosections or wholemounts by a routine immunohistochemical method for visinin (cones), opsin (rods), tyrosine hydroxylase (dopaminergic cells) and proliferating cell nuclear antigen (PCNA), at various intervals after intravitreal injection with TM (1.0 micrograms/eye). On some thin sections, autoradiographic study was combined following intravitreal injection with [3H]thymidine (TdR, 0.1 microCi/eye). The dose of TM used heavily destroyed cones and rods only in the treated retinas 2-15 days after injection, the photoreceptors being renewed for further 15-20 days. Approximately in parallel, ERGs were largely impaired 2-10 days after TM injection and recovered for 10-20 days. However, intravitreal TM altered the distribution and density of PCNA-ir nuclei in both treated and untreated retinas. The density of PCNA-ir nuclei reduced at first (on days 1 and 2), and then clustered and rapidly increased on days 3-5 and maintained at high levels with diffuse distribution over the whole area, particularly in the treated retinas, up to 60 days after TM injection; the maximum peak of 3.7 and 20 times the initial level was seen on day 20 in the outer nuclear layer (ONL) and inner nuclear layer (INL), respectively. PCNA-ir nuclei were found to be abundant in the ONL even after the photoreceptors and ERGs had been restored in the treated retinas on day 20, suggesting a kind of overproduction of retinal cells. The autoradiographic study provided comparable results to those obtained with PCNA immunohistochemistry. The mechanism by which damage to the treated retina causes rod precursor cells to proliferate in the untreated retina remains unresolved.     

Insulin resistance in nonobese Japanese women with polycystic ovary syndrome is associated with poorer glucose tolerance,delayed insulin secretion,and enhanced insulin response

PurposeTo determine the prevalence of insulin resistance (IR) and impaired glucose tolerance (IGT) in PCOS patients, the optimal screening method, and to compare our findings between nonobese and obese Japanese women with PCOS.MethodsNinety‐eight PCOS patients were included in this research from 2006 to 2013. Glucose tolerance test (OGTT) was performed. Serum glucose and insulin concentration were assayed before and 30, 60, and 120 min after taking 75 g of glucose.ResultsAll examined metabolic parameters were significantly favorable in the nonobese subjects, below 25 kg/m². HOMA‐IR, fasting insulin, glucose₁₂₀, and insulin₁₂₀ showed strong correlations with BMI. A total of 1.4 % of nonobese women had IR based on fasting insulin or HOMA‐IR. However, 15.5 % (11/71) of nonobese women had IR as determined by a continuous increase of serum insulin level in OGTT. In comparison, the prevalence of IR among the obese women ranged from 41 to 59 %. AUC_glucose, glucose₆₀, glucose₁₂₀, and insulin₁₂₀ in nonobese women with a continuous insulin increase were higher than those without such a continuous increase.ConclusionsAll examined metabolic parameters were significantly correlated with BMI. As the presence of a continuous increase of insulin level reflects to some degree poorer glucose tolerance, delayed insulin secretion, and enhanced insulin response compared with non‐continuous insulin increase, OGTT might not been excluded to determine IR and IGT for nonobese women with PCOS.     

Activated T lymphocyte subsets in experimental allergic neuritis

Changes in activated T cell subsets in peripheral blood were examined during the course of experimental allergic neuritis (EAN), using two-color immunofluorescence flow cytometry. Both CD4+ and CD8+ activated T cells decreased transiently before the onset of clinical signs, and increased just around the time of onset of the disease. In contrast, during the recovery phase, the numbers of CD4+ activated T cells returned to the normal range, whereas CD8+ activated T cells continued to increase. These findings imply that activation of CD4+ helper/inducer cells contributes mainly to the evolution of EAN, and that of CD8+ suppressor cells are necessary for recovery.     

Involvement of interleukin-1 in the inhibition of in vivo insulin release: possible role of adrenal glands

The effect of recombinant human interleukin-1 beta (rhIL-1b) on in vivo insulin secretion was examined in intact and adrenalectomized (ADX) rats under conscious and pentobarbital anesthetized conditions. In conscious rats, rhIL-1b dose-dependently decreased blood glucose levels at 2 h in both groups and significantly inhibited insulin release only at doses of 1 and 10 micrograms/kg in ADX rats. Under pentobarbital anesthesia, rhIL-1b administration decreased blood glucose levels 2 h later in both intact and ADX rats and resulted in severe hypoglycemia in ADX rats. At 2 h later, rhIL-1b significantly suppressed insulin release by pentobarbital injection in both intact and ADX rats. It is concluded that rhIL-1b suppresses in vivo insulin secretion in conscious ADX and anesthetized rats.     

Coronary flow characteristics in hypertrophic cardiomyopathy--a study with Doppler catheter]

We compared the pattern and reserve of coronary flow in 8 cases of hypertrophic non-obstructive cardiomyopathy (H) with those in 20 cases of chest pain not accompanied by organic heart disease (N). A catheter-tip Doppler velocimeter was positioned in the proximal portion of the left anterior descending (LAD), circumflex (LCX) and right coronary (RCA) arteries. Coronary flow velocity (Vs: systolic peak, Vd: diastolic peak, Vm: mean) was recorded and the area under the velocity curve was divided into systole (* s) and diastole (* d). The time interval between the dicrotic notch in aortic pressure and the peak of diastolic flow velocity was measured (Tpv). Vm was measured before and after intracoronary injection of 6 ml of contrast media, and peak to resting velocity ratio (PRVR) was calculated as an index of coronary flow reserve. Result: In LAD, N showed diastolic predominant coronary flow pattern without backward flow. In H, diastolic predominance was more prominent with systolic backward flow, resulting in decrease in * s/* d(H: 0.07 +/- 0.04, N: 0.25 +/- 0.02, p less than 0.01). In H, Vd (H: 20.1 +/- 2.8, N: 9.2 +/- 1.4 cm/sec, p less than 0.05) and Vm(H: 9.5 +/- 1.3, N: 4.9 +/- 0.7 cm/sec, p less than 0.05) were higher, while PRVR was lower (H: 1.7 +/- 0.1, N: 2.6 +/- 0.1, p less than 0.05). In both N and H, the flow pattern of LCX was diastolic predominant with two peaks (one in systole and the other in diastole).(ABSTRACT TRUNCATED AT 250 WORDS)     

A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers

A late phase II study of CPT-11, a new derivative of camptothecin, in uterine cervical cancer and ovarian cancer was carried out by a cooperative study group at 26 institutions. Out of 144 patients enrolled, total cases were 110, involving 55 uterine cervical cancers and 55 ovarian cancers. In uterine cervical cancer, 5 cases of complete response (CR) and 8 cases of partial response (PR) were observed, with a response rate of 23.6% and a CR rate of 9.1%. In ovarian cancer, 13 cases of PR were observed, response rate was 23.6%. Both in uterine cervical cancer and ovarian cancer, the 95% confidence interval of response rate was 12.4-34.8%. In cases having undergone previous chemotherapy including platinum, derivatives, the response rate in ovarian cancer was 23.1% (12/52). In cases of uterine cervical cancer having previous radiotherapy, the response rate was 26.8% (11/41). In ovarian cancer of various histological types, a response was observed for not only serous cystadenocarcinoma but also mucinous cystadenocarcinoma, etc. A response was observed in distant metastatic lesions such as lung metastasis as well as primary lesion in uterine cervical cancer and ovarian cancer. Major adverse reactions were leukopenia, nausea and vomiting, diarrhea and anorexia, and these incidences (grade 2 or more) were 87.3, 60.3, 44.0 and 67.2%, respectively. Since some patients experienced severe adverse reactions, caution should be taken in treatment with CPT-11. Besides these reactions, alopecia was observed (33.1%), but severe adverse reactions such as nephropathy were not found. No significant difference in the efficacy and adverse reactions were observed between administration methods; A, 100 mg/m2 once weekly and B, 150 mg/m2 once every 2 weeks. Both were thought to be clinically useful. These results suggest that CPT-11 is clinically effective against uterine cervical cancer and ovarian cancer.