The antioxidant/anti-inflammatory protective effects of rutin against ethanol-induced testicular perturbation in rats: Involvement of the immunosuppressive indoleamine 2,3-dioxygenase

This study investigated the influence of rutin against EtOH-induced testicular impairment in rats and the involvement of the indole-aminergic pathway. Four groups of eight rats each were orally exposed to drinking water (Group 1), EtOH (5 g/kg bwt, Group 2), R (5 g/kg bwt, Group 3), and EtOH + R (5 g/kg bwt + 50 mg/kg bwt, Group 4) via gavage for 15 days. Results showed that exposure to EtOH significantly (p < 0.0001) reduced the testicular antioxidant system and increased lipid peroxidation (LPO) relative to control. We observed a significant (p < 0.0001) increase in the inflammatory biomarkers, with attendant disruption in the testicular histological structure and concomitant elevation in the activities of indoleamine 2,3-dioxygenase (IDO), in comparison with control and no noticeable effects in tryptophan 2,3-dioxygenase (TDO) activity across the groups. Rutin-only exposed group did not show any alteration in the measured parameters when compared with the control. Rutin co-exposure augmented the antioxidant system, prevented histological damage, reduced LPO and inflammation, and thus, lowered EtOH-mediated increase in IDO activity, compared with control. Overall, these findings reveal the involvement of the indole-aminergic pathway in rutin's protective influence against EtOH-induced testicular impairment in rats.     

Evaluation of the clinical performance of OncoPredict HPV® SCR assay within the VALGENT-2 framework

Human papillomavirus (HPV) assays used in cervical cancer screening should be clinically validated according to international criteria. OncoPredict HPV® Screening (SCR) is a partial genotyping multiplex real-time PCR assay targeting E6/E7 genes of 13 high-risk (hr) HPVs. OncoPredict HPV® SCR (index assay) identifies HPV-16 and HPV-18 separately, 11 other hrHPV in aggregate and includes quality controls for sample adequacy, DNA extraction efficiency and PCR inhibition. 1300 VALGENT-2 study samples (from women aged 20–60 attending the Scottish cervical cancer screening program) were tested with the index assay and the GP5+/6+ PCR enzyme immunoassay (standard comparator assay). Non-inferior accuracy detecting cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) of the index versus comparator was verified. Intra- and interlaboratory reproducibility of the index was evaluated by overall concordance and Cohen's kappa, using a sub-population (n = 526). Relative sensitivity and specificity for CIN2+ of the index versus comparator were 1.01 (95% confidence interval [CI]: 0.99–1.03) and 1.02 (95% CI: 1.0–1.04), respectively. Noninferiority p values were all ≤0.05, except for CIN3+ in patients ≥30 years. Excellent intra- and interlaboratory reproducibility was shown with concordance >98% and kappas >0.95. OncoPredict HPV® SCR fulfills the three international validation criteria for hrHPV DNA tests in cervical cancer screening.     

Rutin ameliorates oxidative stress and preserves hepatic and renal functions following exposure to cadmium and ethanol

Context: Rutin (RUT) is an antioxidant flavonoid with well-known metal chelating potentials.

Objective: This study was designed to evaluate the protective effects of RUT against cadmium (Cd)?+?ethanol (EtOH)-induced hepatic and renal toxicity in rats.

Materials and methods: Wistar rats were treated with Cd (50?mg/kg) alone or in combination with EtOH (5?mg/kg) and RUT (25, 50 and 100?mg/kg) for 15?days. After treatment, the liver, kidney and serum were removed for biochemical assays by spectrophotometric methods.

Results: Serum, hepatic and renal malondialdehyde (MDA) levels were highest in the Cd?+?EtOH group and lowest in Cd?+?EtOH animals co-treated with the highest dose of RUT (2.98?±?0.34, 10.08?±?2.32, 4.99?±?1.21 vs. 1.69?±?0.33, 6.13?±?0.28, 3.66?±?1.12?μmol MDA/mg protein, respectively). The serum level of Cd was increased in the Cd?+?EtOH treated animals compared to Cd?+?EtOH animals co-treated with 100?mg/kg RUT (2.54?±?0.08 vs. 1.28?±?0.04?ppm). Furthermore, RUT at the highest dose protected against Cd?+?EtOH-induced elevation of bilirubin and uric acid levels as well as activities of lactate dehydrogenase and γ-glutamyl transferase (62.86?±?2.74 vs. 122.52?±?6.35?µmol/L; 1.77?±?0.35 vs. 3.23?±?0.55?mmol/L; 9.56?±?1.22 vs. 16.21?±?1.64?U/L; 288.92?±?40.12 vs. 159.8?±?18.01?U/L). The histo-pathological changes in the liver and kidney were also reduced in the Cd?+?EtOH animals co-treated with RUT in a dose-dependent manner.

Discussion and conclusion: RUT protected against the combined effects of Cd?+?EtOH on hepatic and renal functions and improved the antioxidant defence system in the blood.     

Effects of inhaled corticosteroid on bone turnover in children with bronchial asthma

Long-term usage of systemic steroids is associated with multiple side effects. One of the major morbidities is due to its effect on bone metabolism leading to bone loss and resulting in skeletal fractures. This study was conducted to determine the effects of inhaled steroids on bone mineral density (BMD) and biochemical bone markers. Twenty-four children with frequent episodic or mild persistent asthma who satisfied the clinical criteria for starting on inhaled corticosteroids (ICS) were enrolled into the study. The BMD scan was done using dual energy X-ray absorptiometry, prior to starting ICS therapy and 6 months later. Biochemical markers of bone metabolism, (i) serum osteocalcin as a bone formation marker, and (ii) urinary deoxypyridinoline (Upd) as a bone resorption marker, were taken prior to ICS treatment and at 2 monthly intervals. The biochemical markers were all taken in the morning. Twenty-four, age- and sex-matched children with mild episodic asthma, not requiring ICS, were used as controls for the BMD measurements. The BMD scan was done upon enrollment into the study and 6 months later. Twenty-four children on ICS and 24 controls completed the study. The subjects were on a mean dose of beclomethasone dipropionate (BDP) 0.4 mg/day. One subject needed a short course of Prednisolone in the early treatment period. None of the controls needed oral steroid therapy. One child in the control group sustained a greenstick fracture after an accidental fall. The mean rate of change of BMD was 1.8% +/- 12.3 in the subjects on BDP. This was lower than the 6.1% +/- 10.6 among the control subjects. However, this difference did not reach statistical significance (P = 0.16). There was a significant increase in serum osteocalcin level after 6 months of BDP treatment from 66.83 +/- 22.71 ng/mL to 81.61 +/- 24.66 ng/mL (P < 0.005). There was a decline in Upd from 36.2 +/- 47.1 nmol/mmol creatinine to 21.4 +/- 6.92 nmol/mmol creatinine. However, this did not reach statistical significance. There was no difference in the statural gain between the subjects on ICS and their controls. This study showed that 6 months of ICS therapy (mean dose 0.4 mg/day) had no significant adverse effect on bone metabolism in asthmatic children.     

Carriage rate of hepatitis-B surface antigen (HBsAg) in an urban community in Jos, Plateau State, Nigeria

The carriage rate of Hepatitis-B surface antigen (HBsAg) in an urban community in Jos, the Plateau State capital, was studied to obtain the pattern of Hepatitis-beta virus (HBV) spread within the community. HBsAg screening was performed on a consecutive sample of 524 apparently healthy individuals (293 males and 231 females) aged 15-65 years who voluntarily turned up for the survey. Fifty-four (10.3%) were HBsAg positive by ELISA. The carriage rate in females 30/231 (13.0%) was significantly higher than in the males 24/293 (8.2%) (p<0.05). In relation to age, 14/144 (9.7%) were aged <20 years, 11/121 (9.1%) were 21-30 years, 7/115 (6.1%) were 31-40 years, 14/89 (15.7%) were 41-50 years, 2/27 (7.4%) were 51-60 years and 6/28 (21.4%) were >61 years. In relation to marital status, carriage rate was highest among the divorced/widowed group (12.5%) followed by the married group (10.6%). Carriage rates in relation to occupation showed that infection was highest among traders (13.7%) and students (13.2%). The survey therefore confirms the endemicity of HBV infection in Jos and describes the groups that are at risk. This calls for health education of the general population on preventive measures to check the spread of the virus in the community.     

Reduced Levels of Nitric Oxide Metabolites in Cerebrospinal Fluid Are Associated with Equine Protozoal Myeloencephalitis

Equine protozoal myeloencephalitis (EPM) is a disease of horses that is primarily associated with infection with the apicomplexan Sarcocystis neurona. Infection with this parasite alone is not sufficient to induce the disease, and the mechanism of neuropathogenesis associated with EPM has not been reported. Nitric oxide (NO) functions as a neurotransmitter, a vasodilator, and an immune effector and is produced in response to several parasitic protozoa. The purpose of this work was to determine if the concentration of NO metabolites (NO_x⁻) in the cerebrospinal fluid (CSF) is correlated with the development of EPM. CSF NO_x⁻ levels were measured before and after transport-stressed, acclimated, or dexamethasone-treated horses (n = 3 per group) were experimentally infected with S. neurona sporocysts. CSF NO_x⁻ levels were also compared between horses that were diagnosed with EPM after natural infection with S. neurona and horses that did not have clinical signs of disease or that showed no evidence of infection with the parasite (n = 105). Among the experimentally infected animals, the mean CSF NO_x⁻ levels of the transport-stressed group, which had the most severe clinical signs, was reduced after infection, while these values were found to increase after infection in the remaining groups that had less severe signs of EPM. Under natural conditions, horses with EPM (n = 65) had a lower mean CSF NO_x⁻ concentration than clinically normal horses with antibodies (Abs) against S. neurona (n = 15) in CSF, and horses that developed ataxia (n = 81) had a significantly lower mean CSF NO_x⁻ concentration than horses that did not have neurologic signs (n = 24). In conclusion, lower CSF NO_x⁻ levels were associated with clinical EPM, suggesting that measurement of CSF NO_x⁻ levels could improve the accuracy of diagnostic tests that are based upon detection of S. neurona-specific Abs in CSF alone and that reduced NO levels could be causatively related to the development of EPM.