Protective effect of 2-aminoethyl diphenylborinate on acute ischemia–reperfusion injury in the rat kidney

Background

To investigate the protective effect of 2-aminoethyl diphenylborinate (2-APB) against ischemia–reperfusion (I/R) injury in the rat kidney by an experimental study.

Materials and methods

Thirty male Sprague-Dawley rats were randomly divided into the following three groups: (1) sham group, (2) I/R group, and (3) I/R + 2-APB group. Renal I/R injury was induced by clamping the left renal pedicle for 45 min after right nephrectomy, followed by 3 h of reperfusion. The therapeutic agent 2-APB was administered intravenously at a dose of 2 mg/kg 10 min before renal ischemia. Glutathione, superoxide dismutase, total antioxidant capacity, malondialdehyde, tumor necrosis factor α, interleukin 6, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were measured from blood samples, and the rats were sacrificed subsequently. Tissue samples were scored histopathologically. Visualization of apoptotic cells was performed using the terminal deoxynucleotidyl transferase dUTP nick end labeling staining method.

Results

2-APB significantly reduced serum malondialdehyde, tumor necrosis factor α, interleukin 6, aspartate aminotransferase, alanine aminotransferase, and creatinine levels in the I/R injury group. However, glutathione, superoxide dismutase, and total antioxidant capacity levels increased significantly. Histopathologic scores were significantly better and the rate of apoptosis was lower in the 2-APB group.

Conclusions

2-APB reduces oxidative stress and damage caused by renal I/R injury. The results of this study demonstrate that 2-APB can be used as an effective agent against I/R injury in the kidney.     

The importance of caregivers in the outcome of pediatric HIV management,Mombasa, Kenya

We assessed programmatic gaps that prevent the optimal treatment of pediatric HIV infection despite free antiretroviral care in Kenya. Of 626 HIV-infected Kenyan children, the median age was five years, 54% were male and the mortality rate was 3.2 per 100 person-years. A total of 380 (61%) children initiated antiretroviral therapy (ART) during the study period. Among the 246 children who never started ART, 129 (52%) met the criteria for ART initiation. Immunologic failure occurred in 20% of children who received ART for >24 weeks. In multivariate analysis, immunological failure was associated with having nonimmediate relative or unrelated caregivers accompanying the child to clinic (AOR = 69.16, p = 0.008). Having ≥3 types of accompanying caregivers was also associated with virologic failure in multivariate analysis (AOR = 3.84, p = 0.03). The lost to follow-up rate was 8.7/100 persons-years for the entire cohort, and significantly higher (17.7/100 persons-years) among children not on ART (p < 0.001). Among children who do initiate ART, those with the best treatment outcomes were those who had a limited number of close relatives as caregivers and good adherence to ART. Focus on early ART initiation and education of the right caregiver will likely improve retention and quality of pediatric HIV care in Kenya.     

The effects of prenatal methylmercury exposure on trace element and antioxidant levels in rats following 6-hydroxydopamine-induced neuronal insult

Methylmercury (MeHg) is a metal toxin found commonly in the environment. Studies have shown severe neurotoxic effects of MeHg poisoning especially during pregnancy where it crosses the foetoplacental and the blood brain barrier of the foetus leading to neurodevelopmental deficits in the offspring. These deficits may predispose offspring to neurodegenerative diseases later in life. In this study we investigated the effects of prenatal methylmercury exposure (2.5 mg/L in drinking water from GND 1-GND 21) on the trace element status in the brain of adolescent offspring (PND 28). Total antioxidant capacity (TAC) was measured in their blood plasma. In a separate group of animals that was also exposed prenatally to MeHg, 6-hydroydopamine (6-OHDA) was administered at PND 60 as a model of neuronal insult. Trace element and TAC levels were compared before and after 6-OHDA exposure. Prenatal MeHg treatment alone resulted in significantly higher concentrations of zinc, copper, manganese and selenium in the brain of offspring at PND 28 (p?<?0.05), when compared to controls. In contrast, brain iron levels in MeHg-exposed adolescent offspring were significantly lower than their controls (p?<?0.05). Following 6-OHDA exposure, the levels of iron, zinc, copper and manganese were increased compared to sham-lesioned offspring (p?<?0.05). Prenatal MeHg exposure further increased these trace element levels thereby promoting toxicity (p?<?0.05). Total antioxidant capacity was not significantly different in MeHg and control groups prior to lesion. However, following 6-OHDA administration, MeHg-exposed animals had a significantly lower TAC than that of controls (p?<?0.05). Brain TAC levels were higher in adult male rats than in female rats during adolescence however male rats that had been exposed to MeHg in utero failed to show this increase at PND 74. Prenatal MeHg exposure results in trace element dyshomeostasis in the brain of offspring and reduces total antioxidant capacity. This may reflect a mechanism by which methylmercury exerts its neurotoxicity and/or predispose offspring to further neurological insults during adulthood.     

Positive Airway Pressure Adherence in Patients with Obstructive Sleep Apnea with Schizophrenia

Introduction

To determine the 1-year and 3-year adherence rates with Positive Airway Pressure (PAP) therapy in patients with schizophrenia compared to matched controls.

Methods

A case–control retrospective analysis was performed in a Veterans Affairs hospital. All symptomatic patients with schizophrenia ever started on PAP therapy between 2007 and 2015 were compared with controls matched for severity of sleep apnea based on AHI, BMI, and age at the time of diagnosis.

Results

Total number of subjects in both groups was 39. Mean AHI among cases and controls was 27.63 ± 22.16 and 33.59 ± 44.04 (p = 0.32), mean BMI was 34.91 ± 5.87 and 33.92 ± 5.21 (p = 0.43), and mean age at diagnosis was 53.6 ± 11.75 and 55.97 ± 11.92 (p = 0.36), respectively. There was no statistically significant difference in PAP use between patients with schizophrenia and controls at 1-year (percent days device use > 4 h—36.43% ± 31.41 vs. 49.09% ± 38.76; p = 0.17) and 3-year (percent days device use > 4 h—42.43 ± 35.50 vs. 60.53 ± 38.56; p = 0.089) visits

Conclusions

PAP adherence and usage is not significantly different among patients with schizophrenia compared to matched controls. Therefore, schizophrenia does not appear to influence CPAP compliance.

     

Induction of Rabies Virus Infection in Mice Brain may Up and Down Regulate Type II Interferon gamma via epigenetic modifications

Metabolic Brain Disease - As feared and deadly human diseases globally, Rabies virus contrived mechanisms to escape early immune recognition via suppression of the interferon response. This study,...     

Prenatal diagnosis and postnatal outcome of fetal intracranial hemorrhage

Background

The aim of this study was to present our experience with six cases of fetal intracranial hemorrhage (ICH) in terms of prenatal diagnostic features, and postnatal outcome.

Methods

The database of prenatal diagnosis unit was searched for antenatally diagnosed ICH cases. Maternal characteristics, ultrasound (US), and magnetic resonance imaging (MRI) findings, clinical course, and postnatal outcome were noted.

Results

We evaluated six consecutive cases of fetal ICH. One case was terminated at 24 weeks, and remaining five cases were delivered between 34 and 38 weeks. Five cases (5/6) had intraventricular, and one (1/6) had intraparenchymal hemorrhage. Hemorrhages were right sided in five cases (5/6), left sided in one case (1/6). Dilated and echogenic ventricular wall were the common US findings. No predisposing factor was detected in four of the cases, and intrauterine growth restriction was an underlying factor in two fetuses. Intrauterine progression of the hydrocephaly, and parenchymal thinning was seen in four cases (4/6). In three of four cases (3/4) with progressive grade 3–4 hemorrhage and hydrocephaly, postnatal outcome were dismal, and one case had mild neurological impairment at three months. In one case which had non-progressive mild ventriculomegaly, the lesion regressed after 4 weeks, and had normal short-term outcome

Conclusion

Fetal ICH can be accurately identified and categorized by antenatal sonography, and fetal MRI. Although intrauterine regression or normal short-term postnatal outcome is possible, the outcome is usually poor for fetuses with high grade and/or progressive lesions. Therefore, further studies assessing long-term postnatal outcome are needed