A novel SRD5A2 mutation in an Iranian family with sex development disorder

Disorders of sex development (DSD) are different types of conditions that their accurate diagnosis by using conventional phenotypic and biochemical approaches is a challenging issue. Precise determination of DSD is critical due to the detection of possible life-threatening associated disorders. It may also assist parents in choosing the most suitable management for their affected child. In this study, two affected kids born from consanguineous families who were clinically diagnosed for sex development disorder were investigated for the main cause of the disease. Biochemical analysis failed to make an accurate diagnosis. Karyotype analysis showed an abnormal sex chromosome pattern. Whole exome sequencing was sequentially applied to precisely ascertain the genetic cause of the disease. A novel deletion, g.40936_53878del12943insTG (NG_008365.1), and one known mutation, c.586G>A (p.Gly196Ser), were detected in SRD5A2 gene in case I and case II respectively. Further analysis was performed using polymerase chain reaction, primer walking and Sanger sequencing to detect the nucleotides changes accurately. Segregation analysis in the families confirmed 13kb novel homozygous deletion of SRD5A2 in case I and c.586G>A in case II. The present study confirms the diagnostic value of whole exome sequencing in the detection of DSD aetiology, especially when several differential diagnoses are possible.     

Bioadhesion and biocompatibility evaluations of gelatin and polyacrylic acid as a crosslinked hydrogel in vitro

This study describes the potentiality of crosslinked hydrogels comprised of gelatin and polyacrylic acid (CHGP) as a biological glue for soft tissues and compares its bonding strength with that of fibrin glue. Water-soluble carbodimide (WSC) was used to crosslink the mixture of gelatin and polyacrylic acid (PAA). An addition of PAA to gelatin increases bonding strength and reduces the gelation time and WSC concentration. Increasing the gelatin, WSC and PAA concentration increases the bonding strength. There is a critical concentration to have a maximum bonding strength. The cured hydrogel exhibited sufficient adhesion to mouse skin with a higher bonding strength than fibrin glue. The in vitro test has been done for evaluating CHGP toxicity.     

Inhibitory effect of Thymus caramanicus Jalas on hyperglycemia-induced apoptosis in in vitro and in vivo models of diabetic neuropathic pain

Ethnopharmacological relevance

Since Thymus caramanicus Jalas is used as a folk medicine for the treatment of rheumatism, skin disorders, bacterial infections and diabetes and it contain antioxidant agents, we decided to investigate the possible effects of Thymus caramanicus Jalas (TCJ) extract on in vitro and in vivo models of diabetic neuropathy.

Materials and methods

The high glucose-induced cell injury in Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick and rotarod treadmill assessments were used to determine nociceptive threshold and motor coordination. Cell viability was determined by MTT assay test. Western blotting was performed to measurement of apoptosis markers.

Results

The data showed that elevation of glucose consecutively increases functional cell injury and apoptosis. Furthermore, diabetic rats developed thermal hyperalgesia and motor deficit. Activated caspase 3, cytochrome c release and Bax/Bcl-2 ratio were significantly increased in high glucose-treated PC12 cells and in spinal cord of diabetic animals. TCJ extract (60 and 80 µg/ml) attenuates high glucose-induced PC12 cells damage and apoptosis. In diabetic animals, TCJ extract at daily doses of 100 and 150 mg/kg ameliorated hyperalgesia and suppressed spinal apoptosis.

Conclusion

The data indicate that TCJ extract has neuroprotective effects against high glucose-induced neural damage. These protective effects are mediated, at least in part, through attenuation of neural apoptosis and suggest therapeutic potential of TCJ extract in amelioration of diabetic neuropathy.     

New insights into antidiabetic drugs: Possible applications in cancer treatment

Globally at 2014, it was estimated that there was 347 million people with diabetes in which 90 percent of them were diagnosed with type 2 diabetes mellitus (T2DM). Although the association between diabetes mellitus and cancer risk was found about 100 years ago, the issue is not still clear. Many studies especially cohort and case–control studies have suggested a higher risk of cancer in patients with diabetes mainly in those with type 2 diabetes. Insulin concentration is high in these patients, and due to its mitogenic effects, it may be a possible hypotheses for higher risk of cancer in diabetic patients. Therefore, antidiabetic drugs, which are involved in insulin secretion and sensitivity, may have beneficial effects in cancer treatment. Several groups of drugs with different mechanisms of action, mostly prescribed orally, are used for the treatment of type 2 diabetes mellitus including, insulin sensitizers (thiazolidinediones), insulin secretagogues (sulfonylureas), and biguanides. In this review, the possible effects of antidiabetic drugs (biguanides, thiazolidinediones, and sulfonylureas) and some of their mechanisms for overcoming cancer will be discussed.     

A National Experience on Physical Activity Initiatives for Adolescent Girls and their Mothers: CASPIAN Study

Objective

To provide a low-cost and simple model of culturally-appropriate and low cost facilities for improvement of physical activity for girls and their mothers through an after-school program and to determine the changes in anthropometric indexes after this trial.

Methods

This national study was conducted in 2006-2007 in 7 provinces with different socioeconomic situations in Iran. Female students who studied in the 7^th through 10^th grade and their mothers were selected by random cluster sampling. In each province, 24 sessions of after-school aerobic physical activity were held for 90 minutes, two days a week, and 3 months long at school sites in the afternoon.

Findings

The study comprised 410 participants (204 mothers and 206 daughters), with a mean age of 15.86±1.01 and 40.71±6.3 years in girls and their mothers, respectively. The results of the focus group discussions showed that in general, both mothers and daughters were satisfied from the program and found it feasible and successful. After the trial, the indexes of generalized and abdominal obesity improved significantly both in girls and in their mothers (P-value <0.0001 for weight, body mass index and waist circumference).

Conclusion

Our findings may provide a low-cost and simple effective model of motivation for physical activity with targeted interventions for girls and their mothers. We suggest that the success of this trial might be a result of bonding and accompaniment of mothers and daughters. Such model can be integrated in the existing health and education systems to increase the physical activity level.     

Infiltrative lung diseases: Complications of novel antineoplastic agents in patients with hematological malignancies

Infiltrative lung disease is a well-known complication of antineoplastic agents in patients with hematological malignancies. Novel agents are constantly being added to available treatments. The present review discusses different pulmonary syndromes, pathogenesis and management of these novel agents.     

Comparison of a Steady Flow Pump to a Preload Responsive Pulsatile Pump in Left Atrial–to–Aorta Bypass in Canines

A unique preload responsive pulsatile pump was compared to a centrifugal pump in total cardiac support in 25-kg canines (n = 6, each group) in the left atrial-to-aorta mode during 5 h of ventricular fibrillation. With steady flow, there was immediate drop in output from 2.1 +/- 1.0 L/min to 1.4 +/- 0.3 L/min, followed by further reduction to 0.9 +/- 0.2 L/min during 5 h of ventricular fibrillation. With a pulsatile pump, there was no significant reduction from control of 2.4 +/- 0.6 L/min and no decline during 5 h of ventricular fibrillation. With steady flow, systemic vascular resistance (SVR) rose significantly from 1,762 dyne-s-cm-5 immediately on pump to 3,013 dyne-s-cm-5 at 5 h. With physiologic pulsatile flow, significant elevation of SVR did not occur. When stressed, due to diminished left atrial return, the centrifugal pump displayed line chatter and streaks of microbubbles, whereas the pulsatile pump did not. Crystalloid volume replacement with the centrifugal pump was 6.5 +/- 1.9 L, and with the preload responsive pulsatile pump, 5.6 +/- 1.3 L. It is concluded that in the left atrial-to-aorta mode during 5 h of ventricular fibrillation and with comparable volume replacement, total cardiac support of canines is associated with lower SVR with physiologic pulsatile flow and is not accompanied by line chatter and cavitation with this preload responsive pump.     

The ratio of apoB/apoAI, apoB and lipoprotein(a) are the best predictors of stable coronary artery disease.

BACKGROUND: The ratio of low- to high-density lipoprotein-cholesterol (LDL-C/HDL-C) conventionally represents the balance of proatherogenic and anti-atherogenic lipids. However, growing evidence supports the idea that the ratio of apolipoprotein (apo) B/apoAI is a better index for risk assessment of coronary artery disease (CAD). The aim of this study was to evaluate the efficiency of advanced profile of serum (apo)lipoproteins for predicting stable CAD in secondary prevention. METHODS: The study subjects, 138 men and 126 women aged 40-70 years, were classified as CAD cases or controls, according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and extent of lesions in coronary arteries. Serum (apo)lipoproteins were measured by immunoturbidometric and electrophoresis methods. RESULTS: Patients with CAD compared with controls had increased serum levels of triglycerides (2.6+/-2.0 vs. 2.0+/-1.2 mmol/L, p< or =0.005), apoB (1.36+/-0.31 vs. 1.19+/-0.24 g/L, p< or =0.0001), lipoprotein(a) [Lp(a)] (0.69+/-0.60 vs. 0.43+/-0.31 g/L, p< or =0.0001) and apoB/apoAI ratio (1.07+/-0.32 vs. 0.87+/-0.18, p< or =0.0001), and decreased serum levels of HDL-C (1.02+/-0.29 vs. 1.11+/-0.34 mmol/L, p< or =0.03), apoAI (1.32+/-0.22 vs. 1.37+/-0.19 g/L, p< or =0.04) and LDL-C/apoB ratio (0.91+/-0.32 vs. 1.02+/-0.25 mmol/g, p< or =0.01). Multiple logistic regression analysis after adjusting for major risk factors showed that the apoB/apoAI ratio, apoB and Lp(a) were among seven significant and independent determinants of CAD. The area under the receiver operating characteristic (ROC) curves (AUC) as a relative measure of test efficiency was highest and significant for the apoB/apoAI ratio (AUC=0.71, p< or =0.0001), apoB (0.67, p< or =0.0001), Lp(a) (0.63, p< or =0.001), the LDL-C/apoB ratio (0.62, p< or =0.006), triglycerides (0.62, p< or =0.004) and apoAI (0.58, p< or =0.05). ANOVA analysis showed significant association for the apoB/apoAI ratio, apoB, Lp(a) and triglycerides, and moderate association for total cholesterol and its subfractions, with the severity of CAD. CONCLUSIONS: The results indicate that the apoB/apoAI ratio, apoB and Lp(a) are independent risk factors for CAD and are superior to any of the cholesterol ratios. We suggest using the apoB/apoAI ratio as the best marker of CAD in clinical practice.