81 research outputs found
Role of protein kinase C in angiotensin II-induced constriction of renal microvessels
Role of protein kinase C in angiotensin II-induced constriction of renal microvesselsBackgroundAlthough angiotensin II (Ang II) exerts its action through multiple vasomotor mechanisms, the contribution of phosphoinositol hydrolysis products to Ang II-induced renal vasoconstriction remains undetermined.MethodsThe role of protein kinase C (PKC) in Ang II-induced afferent (AFF) and efferent (EFF) arteriolar constriction was examined using the isolated perfused hydronephrotic rat kidney.ResultsAng II (0.3 nmol/L)-induced EFF constriction was refractory to inhibition of voltage-dependent calcium channels by pranidipine (1 μmol/L, 19 ± 2% reversal) but was completely reversed by a PKC inhibitor, chelerythrine (1 μmol/L, 96 ± 2% reversal). Furthermore, direct PKC activation by phorbol myristate acetate (PMA; 1 μmol/L) caused prominent EFF constriction, and this constriction was inhibited by manganese and free calcium medium. In contrast, Ang II-induced AFF constriction was completely abolished by pranidipine (98 ± 4% reversal) and was partially inhibited by chelerythrine (55 ± 3% reversal). Although PMA elicited marked AFF constriction, this constriction was insensitive to the calcium antagonist, but was totally inhibited by manganese or free calcium medium.ConclusionsPKC plays an obligatory role in Ang II-induced EFF constriction that requires extracellular calcium entry through nonselective cation channels. In contrast, in concert with our recent findings demonstrating a complete dilation by thapsigargin, Ang II-induced AFF constriction is mainly mediated by inositol trisphosphate (IP3) and voltage-dependent calcium channel pathways, but could not be attributed to the PKC-activated calcium entry pathway (for example, nonselective cation channels). Rather, Ang II-stimulated PKC may cross-talk to the IP3/voltage-dependent calcium channel pathway and could modulate the vasoconstrictor mechanism of the AFF. Thus, the role of PKC during Ang II stimulation differs in AFF and EFF, which may constitute segmental heterogeneity in the renal microvasculature
Quality of life of children with neurodevelopmental disorders and their parents during the COVID-19 pandemic : a 1-year follow-up study
This study aimed to reveal changes in the quality of life (QOL) of children with neurodevelopmental disorders and their parents, and the interaction between their QOL and parental mental state during the coronavirus 2019 (COVID-19) pandemic. Eighty-nine school-aged children and parents participated in surveys in May 2020 (T1) and May 2021 (T2). The parents completed questionnaires that assessed their QOL, depression, parenting stress, and living conditions. Children's temporary mood status was evaluated using the self-reported visual analog scale (VAS). Children's QOL and VAS at T2 were higher than their QOL at T1. Parents' QOL at T2 was lower than their QOL at T1. Severe parental depression at T1 had a synergistic effect on severe parenting stress and severe depressive state at T2. Additionally, children's high QOL at T1 had a synergistic effect on low parenting stress and children's high QOL at T2. Furthermore, children's low VAS scores and parents' low QOL at T2 were associated with deterioration of family economic status. Children and parents' QOL changed during the prolonged COVID-19 pandemic. Improvement in children's QOL was influenced by reduced maternal depressive symptoms. Public support for parental mental health is important to avoid decreasing QOL.Peer reviewe
Factors related to employment in childhood cancer survivors in Japan: A preliminary study
PurposePrevious research has revealed vocational and academic difficulties in childhood cancer survivors, and explored impact of survivors' medical history and physical function on vocational and academic status. However, we often encounter survivors with similar diagnoses and late effects but different academic or employment statuses. This raises the question of what affects academic attainment and employment other than treatment or late effects. This study aimed to explore factors associated with childhood cancer survivors' employment status and academic achievement.MethodsComprehensive health check-up and questionnaire survey were conducted for 69 survivors who were over the age of 18 and participated in St. Luke's Lifetime cohort study. We obtained survivors' biological function using comprehensive health check-up, neurocognitive states, quality of life, transition readiness, and family function. We conducted univariate analysis (Mann–Whitney U tests or chi-square tests) to compare the differences between the regular workers/students and non-regular workers/unemployed groups. The variables with p-values <0.1 were used as independent variables multivariate logistic regression to explore predictors of employment status and academic attainment.ResultsResult of the univariate analysis, intelligence quotient, SF-8 PCS, transition readiness, family function were used for multivariate logistic regression as independent variables. The stepwise likelihood method was conducted; intelligence quotient (odds ratio [OR] = 1.100; 95% confidence interval [CI] 1.015–1.193; p = 0.021), transition readiness (OR = 0.612; 95% CI 0.396–0.974; p = 0.038), and family function (OR = 2.337; 95% CI 1.175–4.645; p = 0.015) were found to be associated with survivors' regular workers/students in the final regression model.ConclusionLong-term follow-up of pediatric cancer survivors requires the provision of total care, which supports physical, psychological, and social functions to improve health, readiness for transition to self-management, and family functioning
Spacial and temporal dynamics of the volume fraction of the colloidal particles inside a drying sessile drop
Using lubrication theory, drying processes of sessile colloidal droplets on a
solid substrate are studied. A simple model is proposed to describe temporal
dynamics both the shape of the drop and the volume fraction of the colloidal
particles inside the drop. The concentration dependence of the viscosity is
taken into account. It is shown that the final shapes of the drops depend on
both the initial volume fraction of the colloidal particles and the capillary
number. The results of our simulations are in a reasonable agreement with the
published experimental data. The computations for the drops of aqueous solution
of human serum albumin (HSA) are presented.Comment: Submitted to EPJE, 7 pages, 8 figure
Complete Mitochondrial Genome and Phylogeny of Pleistocene MammothMammuthus primigenius
Phylogenetic relationships between the extinct woolly mammoth(Mammuthus primigenius), and the Asian(Elephas maximus) and African savanna(Loxodonta africana) elephants remain unresolved. Here, we report the sequence of the complete mitochondrial genome (16,842 base pairs) of a woolly mammoth extracted from permafrost-preserved remains from the Pleistocene epoch—the oldest mitochondrial genome sequence determined to date. We demonstrate that well-preserved mitochondrial genome fragments, as long as ~1,600–1700 base pairs, can be retrieved from pre-Holocene remains of an extinct species. Phylogenetic reconstruction of the Elephantinae clade suggests thatM. primigenius andE. maximus are sister species that diverged soon after their common ancestor split from theL. africana lineage. Low nucleotide diversity found between independently determined mitochondrial genomic sequences of woolly mammoths separated geographically and in time suggests that north-eastern Siberia was occupied by a relatively homogeneous population ofM. primigenius throughout the late Pleistocene
A multicenter randomized controlled trial to evaluate the efficacy and safety of nelfinavir in patients with mild COVID-19
Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment. The patients were randomly assigned (1:1) to receive oral nelfinavir (750 mg; thrice daily for 14 days) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to viral clearance, confirmed using quantitative reverse-transcription PCR by assessors blinded to the assigned treatment. A total of 123 patients (63 in the nelfinavir group and 60 in the control group) were included. The median time to viral clearance was 8.0 (95% confidence interval [CI], 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI, 7.0 to 10.0) days in the control group, with no significant difference between the treatment groups (hazard ratio, 0.815; 95% CI, 0.563 to 1.182; P = 0.1870). Adverse events were reported in 47 (74.6%) and 20 (33.3%) patients in the nelfinavir and control groups, respectively. The most common adverse event in the nelfinavir group was diarrhea (49.2%). Nelfinavir did not reduce the time to viral clearance in this setting. Our findings indicate that nelfinavir should not be recommended in asymptomatic or mildly symptomatic patients infected with SARS-CoV-2. The study is registered with the Japan Registry of Clinical Trials (jRCT2071200023). IMPORTANCE The anti-HIV drug nelfinavir suppresses the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. However, its efficacy in patients with COVID-19 has not been studied. We conducted a multicenter, randomized controlled trial to evaluate the efficacy and safety of orally administered nelfinavir in patients with asymptomatic or mildly symptomatic COVID-19. Compared to standard-of-care alone, nelfinavir (750 mg, thrice daily) did not reduce the time to viral clearance, viral load, or the time to resolution of symptoms. More patients had adverse events in the nelfinavir group than in the control group (74.6% [47/63 patients] versus 33.3% [20/60 patients]). Our clinical study provides evidence that nelfinavir, despite its antiviral effects on SARS-CoV-2 in vitro, should not be recommended for the treatment of patients with COVID-19 having no or mild symptoms
Intrarenal Oxidative Stress and Augmented Angiotensinogen are Precedent to Renal Injury in Zucker Diabetic Fatty Rats
The Zucker diabetic fatty (ZDF) rat is a model of type II diabetes and metabolic syndrome based on impaired glucose tolerance caused by the inherited insulin-resistance gene. The ZDF rat exhibits progressive nephropathy; however, the detailed mechanisms have remained unclear. This study was performed to examine the possible involvement of enhanced intrarenal angiotensinogen in the development of renal injury in ZDF rats. Genetic pairs of male ZDF rats and control lean rats (N=6 each) were maintained from 12 to 17 weeks of age. At 17 weeks of age, fasting blood glucose and urinary 8-isoprostane levels were significantly higher in ZDF rats compared with the controls. Systolic blood pressure progressively increased in ZDF rats from 120+/-1 to 137+/-1 mmHg during this period. In contrast, systolic blood pressure did not increase in the controls. Kidney angiotensinogen protein levels were significantly increased in ZDF rats compared with the controls (1.83+/-0.34 vs. 1.00+/-0.17, relative ratio). Expression of angiotensin II type 1a receptor mRNA was similar between these groups. The measured indices of renal damage in the present study (glomerular sclerosis, interstitial expansion, glomerular macrophage infiltration, and renal arterial proliferation) were not significantly increased at this stage in ZDF rats. However, we previously showed that the increased reactive oxygen species-related angiotensinogen enhancement plays an important role in the development of renal injury in a genetic salt-sensitive hypertension. Thus, the present data suggest that elevated reactive oxygen species and reactive oxygen species-associated augmentation of intrarenal angiotensinogen may initiate the development of renal injury in ZDF rats.</p
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