Investigation on sodium valproate induced germ cell damage, oxidative stress and genotoxicity in male Swiss mice

Sodium valproate (VPA) is the most widely used antiepileptic drug for the treatment of epilepsy, bipolar psychiatric disorders and migraine. However, long-term VPA treatment has several adverse effects on the reproductive system. The present study was aimed to investigate the possible germ cell toxicity of VPA in mice. Animals were treated with VPA intraperitoneally for 10 and 28 days at the doses of 500 mg/kg-d and 100, 200 and 400 mg/kg-d, respectively, and were sacrificed 24h after the last dose. The germ cell toxicity of VPA was assessed using oxidative stress parameters, sperm count, sperm head morphology, sperm comet assay, 8-oxo-dG expression and histology. VPA treatment significantly decreased the sperm count, testes and epididymis weight and significantly increased the sperm head abnormality, sperm DNA damage, oxidative stress and 8-oxo-dG expression in the testes of mice. The present study illustrates that VPA induced germ cell toxicity in mice.     

Transfusion insurgency: practice change through education and evidence-based recommendations

Background

In 2000, we implemented an evidence-based guideline in the surgical intensive care unit (SICU) using a transfusion threshold of hemoglobin <8 g/dL. We hypothesized that continual education on the transfusion protocol would decrease transfusions.

Methods

We analyzed 2-month samples of admissions in even-numbered years from 1998 to 2006. Any infusion of packed red blood cells (PRBCs) was included.

Results

We analyzed data from 2,138 patients resulting in 5,130 transfusions. Thirty-six patients received >20 U of blood. The only difference between groups occurred in 2006 when renal failure increased. Transfusions decreased from 3.2 ± 0.34 (SE) to 1.7 ± 0.2. The number of patients who received blood also decreased. Mortality and length of stay (LOS) were not different among the groups. Every unit of blood transfused increased the mortality risk by 14%.

Conclusions

Implementation of an evidence-based transfusion guideline reduced the number of infused units and patients transfused without an increase in mortality.     

Risk factors for non-fatal myocardial infarction and cardiac death in incident dialysis patients

Background. The risks of major cardiac events in patients initiatinglong-term dialysis related to prior coronary disease and variousother factors are not well known. Methods. We used United States Renal Data System data to analysethe outcomes of non-fatal myocardial infarction (MI) and cardiacdeath in incident dialysis patients from years 1997 through2001 (n = 214 890). The presence of established coronaryartery disease was determined from the Medical Evidence form,non-fatal MI events were determined from Medicare claims’data and cause of death was determined from the Death Notificationform. Multivariable analyses were performed employing Cox proportionalhazards models using demographics, co-morbidities, laboratoryvariables, prior erythropoietin use, body mass index and typeof dialysis. Results. In patients with prior coronary disease as comparedto those without, the adjusted relative risk of non-fatal MIwas 1.57 (95% CI, 1.5–1.65) and cardiac death was 1.16(95% CI, 1.14–1.18). The 5-year cumulative incidence ofnon-fatal MI was 8.1 and 6% and cardiac death was 48.3 and 40.2%,in patients with and without prior coronary disease, respectively.Amongst important factors, blacks had a lower risk of non-fatalMI and cardiac death as compared to whites. A history of hypertensionconferred a lower independent risk of cardiac death events.Lower haemoglobin, higher albumin and higher creatinine valueseach conferred a lower independent risk of non-fatal MI andcardiac death. Conclusions. Incident dialysis subjects with prior coronarydisease have a risk of non-fatal MI greater by 57% and cardiacdeath by 16% as compared to subjects without prior coronarydisease. In both populations, the competing risk of cardiacdeath is several-fold greater than that of non-fatal MI. Thereare several factors suggesting reverse epidemiology phenomenawith respect to major cardiac events in the dialysis population.     

Uncomplicated and complicated obsessive-compulsive disorder: an exploratory study from India

Obsessive-compulsive disorder (OCD) is frequently associated with comorbid Axis I disorders. Little data are available from the Indian subcontinent. Recent studies have raised the possibility of different characteristics of Indian patients with OCD. Furthermore, very few studies have compared OCD with comorbid Axis I disorders with pure OCD. This cross-sectional exploratory study was carried out with the objective of studying Axis I comorbidity in OCD in an Indian setting. It also aimed to compare OCD with comorbid Axis I disorder vs pure OCD on multiple parameters. Fifty-four patients with OCD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) were included in the present study. Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-I was used to assess Axis I comorbidity. The patients were evaluated on different standardized scales measuring obsessive-compulsive, anxiety, and depressive symptomatology. Axis I comorbidity was seen in 64.8% of the sample. The most common comorbid disorders were depression (38.88%), panic disorder (7.40%), and phobias (7.40%). No significant differences were observed on sociodemographic variables, but on psychopathological scales, the OCD complicated with Axis I disorders subgroup scored higher except in the Yale-Brown Obsessive Compulsive Scale compulsion subscale. Frequency and pattern of Axis I comorbidity in OCD in an Indian setting are not different from the rest of the world. Long-term prospective multicenter epidemiological studies are required to understand the development and influence of comorbidity in OCD.     

Deviations in gait pattern in experimental models of hindlimb paresis shown by a novel pressure mapping system

Injuries to the central and peripheral nervous system result in varying degrees of paresis and as such alter gait. We developed novel quantitative measures to assess compensatory patterns of gait in experimental models of unilateral and bilateral hindlimb paresis. We hypothesized that hindlimb paresis results in unique alterations in the gait cycle that reflect the symmetry of the initial lesion. To test this hypothesis, adult, male Sprague-Dawley rats were subjected to a unilateral sciatic nerve crush injury or a moderately severe spinal cord contusion injury at T8. Kinematic and timing parameters were captured simultaneously in all four limbs and alterations in gait were then compared to relevant sham controls. Gait analysis consisted of walking trials through a gait tunnel positioned over a Tekscan pressure sensor grid. After sciatic nerve injury, animals unweighted the injured limb by shifting their center of mass toward the contralateral forelimb and hindlimb. These changes in weight-bearing occurred simultaneously with an increase in stance time on the contralateral limbs. As might be expected spinal cord injured animals unweighted their hindlimbs, as shown by reduced hindlimb contact force and contact pressure. These adjustments coincided with a shortening of forelimb stance time and stride length. These findings show both alterations and compensatory changes in gait that reflect the symmetry of the initial injury.