TNF-α gene polymorphisms in Iranian Azeri Turkish patients with Behcet’s Disease

Genetic factors that predispose individuals to Behcet’s disease (BD) are considered to play an important role in the development of the disease. The serum level of tumor necrosis factor (TNF) is elevated in patients with BD, and a dramatic response to anti-TNF-α antibody treatment further supports the role of TNF in BD. We investigated the distribution of TNF-α promoter −1031T/C and −308G/A polymorphisms in 53 BD patients of Iranian Azeri Turks and 79 matched healthy controls, via the PCR–RFLP technique. The frequency of the TNF-α −1031C allele was significantly higher in Behcet’s patients than in healthy controls (p < 0.0001, OR = 3.08; 95% CI = 1.73–5.47), whereas the frequency of the TNF-α −308A allele was similar in the two compared groups. The frequency of CG haplotype was significantly higher (p < 0.0001, OR = 3.42; 95% CI = 1.89–6.18), and that of the TA haplotype was significantly lower in BD patients than in healthy controls. These results suggest that TNF-α is a susceptibility gene for BD in patients from Iranian Azeri Turk ethnic group.     

Small-fibre neuropathy in men with type 1 diabetes and erectile dysfunction: a cross-sectional study

Aims/hypothesis

The aim of this study was to identify the contribution of small- and large-fibre neuropathy to erectile dysfunction in men with type 1 diabetes mellitus.

Methods

A total of 70 participants (29 without and 41 with erectile dysfunction) with type 1 diabetes and 34 age-matched control participants underwent a comprehensive assessment of large- and small-fibre neuropathy.

Results

The prevalence of erectile dysfunction in participants with type 1 diabetes was 58.6%. After adjusting for age, participants with type 1 diabetes and erectile dysfunction had a significantly higher score on the Neuropathy Symptom Profile (mean ± SEM 5.3 ± 0.9 vs 1.8 ± 1.2, p = 0.03), a higher vibration perception threshold (18.3 ± 1.9 vs 10.7 ± 2.4 V, p = 0.02), and a lower sural nerve amplitude (5.0 ± 1.1 vs 11.7 ± 1.5 mV, p = 0.002), peroneal nerve amplitude (2.1 ± 0.4 vs 4.7 ± 0.5 mV, p < 0.001) and peroneal nerve conduction velocity (34.8 ± 1.5 vs 41.9 ± 2.0 m/s, p = 0.01) compared with those without erectile dysfunction. There was also evidence of a marked small-fibre neuropathy with an impaired cold threshold (19.7 ± 1.4°C vs 27.3 ± 1.8°C, p = 0.003), warm threshold (42.9 ± 0.8°C vs 39.0 ± 0.9°C, p = 0.005) and heart rate variability (21.5 ± 3.1 vs 30.0 ± 3.7 beats/min, p = 0.001) and reduced intraepidermal nerve fibre density (2.8 ± 0.7 vs 5.9 ± 0.7/mm, p = 0.008), corneal nerve fibre density (12.6 ± 1.5 vs 23.9 ± 2.0/mm², p < 0.001), corneal nerve branch density (12.7 ± 2.5 vs 31.6 ± 3.3/mm², p < 0.001) and corneal nerve fibre length (8.3 ± 0.7 vs 14.5 ± 1.0 mm/mm², p < 0.001) in participants with type 1 diabetes and erectile dysfunction. Erectile dysfunction correlated significantly with measures of both large- and small-fibre neuropathy.

Conclusions/interpretation

Small-fibre neuropathy is prominent in patients with type 1 diabetes, and is associated with erectile dysfunction and can be objectively quantified using corneal confocal microscopy. This may allow the identification of patients who are less likely to respond to conventional therapies such as phosphodiesterase type 5 inhibitors.

     

The Effect of Sleep Deprivation on Cardiac Function and Tolerance to Ischemia-Reperfusion Injury in Male Rats

Background

Sleep deprivation (SD) is strongly associated with elevated risk for cardiovascular disease.

Objective

To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR) injury in male rats.

Method

SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP); heart rate (HR); and the maximum rate of increase and decrease of left ventricular pressure (±dp/dt). Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP) was measured at start and end of study.

Results

In the SD group, the baseline levels of LVDP (19%), +dp/dt (18%), and -dp/dt (21%) were significantly (p < 0.05) lower, and HR (32%) was significantly higher compared to the controls. After ischemia, hearts from SD group displayed a significant increase in HR together with a low hemodynamic function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days.

Conclusion

Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR.     

Role of inducible nitric oxide synthase in myocardial ischemia-reperfusion injury in sleep-deprived rats

Introduction

REM sleep deprivation (SD) decreases tolerance of the rat heart to ischemia-reperfusion (IR) injury; the underlying mechanisms, however, are unknown. This study aimed at determining whether changes in iNOS, Bax, and Bcl-2 gene expression are involved in this detrimental effect.

Method

SD was induced by flowerpot technique for a period of 4 days. This method is simple and able to induce sleep fragmentation which occurs as one of the sleep disorder symptoms in clinical conditions. The hearts of control and SD rats were perfused in Langendorff apparatus and subjected to 30 min ischemia, followed by 90 min reperfusion. The hemodynamic parameters (left ventricular developed pressure (LVDP), and ± dp/dt), NOx (nitrite + nitrate) level, infarct size, and mRNA expression of iNOS, Bax, and Bcl-2 were measured after IR.

Results

SD rats had lower recovery of post-ischemic LVDP (32.8 ± 2.5 vs. 51.5 ± 2.1 mmHg; P < 0.05), + dp/dt (1555 ± 66 vs. 1119.5 ± 87 mmHg/s; P < 0.05) and ? dp/dt (1437 ± 65 vs. 888 ± 162 mmHg/s; P < 0.05). SD rats also had higher NOx levels (41.4 ± 3.1 vs. 22.4 ± 3.6 μmol/L; P < 0.05) and infarct size (64.3 ± 2.3 vs. 38.3 ± 1.6%; P < 0.05) after IR, which along with LVDP, ± dp/dt restored to near normal status in the presence of aminoguanidine, a selective iNOS inhibitor. Following IR, expression of iNOS and Bax increased and Bcl-2 decreased (502, 372, and 54%, respectively) in SD rats; whereas in the presence of aminoguanidine, expression of iNOS and Bax significantly decreased and Bcl-2 increased (165, 168, and 19%, respectively).

Conclusion

Higher expression of iNOS and subsequent increase in apoptosis in the hearts after IR may contribute to less tolerance to myocardial IR injury in SD rats.

     

Prevalence and correlates of snoring in adolescents

Snoring can occur alone or it may be the presenting feature of Obstructive Sleep Apnea and other common chronic conditions. In our study, we aimed to estimate the prevalence and correlates of snoring in adolescent students in Tehran, Iran. A cross-sectional study was designed and students were selected from 20 secondary and high schools, in 5 different zones in Tehran in order to have a representative sample of the adolescent population. A total of 2900 students (1200 male and 1700 female students) 11-17 year-old who were attending secondary and high schools were investigated. Information was collected via a structured face-to-face interview, based on a questionnaire. In addition to snoring, nocturnal cough, asthma-related symptoms, and daytime symptoms were also questioned. BMI was measured by two trained physicians. The prevalence of snoring was 7.9% (4.8% in girls and 12.4% in boys). The prevalence of snoring was significantly higher among males (P< 0.05). Snoring was positively associated with asthma and nocturnal cough. Overweight/obese adolescents had significantly higher rates of snoring and asthma symptoms. Prevalence of daytime symptoms increased significantly in the snoring group.These results suggest that snoring is associated with multiple factors in adolescents. We conclude that the prevalence of snoring is relatively high in children of this region. This highlights the need for awareness among physicians about the problem of sleep-disordered breathing, especially in children with asthma and obesity, and also the need for further studies to measure the prevalence of sleep breathing disorders among Iranians.     

Lithium and valproate protect against dextro-amphetamine induced brain choline concentration changes in bipolar disorder patients.

BACKGROUND: Lithium may affect brain choline concentrations, and this effect has been proposed to potentially explain its clinical efficacy. Since dextro-amphetamine is a useful human model of mania, we were interested in determining firstly whether dextro-amphetamine would alter brain choline concentrations, and secondly to determine if lithium would protect against any such changes in bipolar patients. In addition, we wanted to determine if valproate would also have any effects upon choline levels. METHODS: Healthy controls (n=18) were compared with euthymic Bipolar Disorder patients (Type I and Type II) who were taking lithium (n=14) or valproate (n=11). We utilized (1)H-magnetic resonance spectroscopy ((1)H-MRS) in a 3.0T scanner to examine brain choline/phosphocholine+creatine (Cho/Cr) ratios. Changes in this ratio were measured to determine any changes in choline concentrations in the temporal lobe. RESULTS: The results showed that administration of dextro-amphetamine decreased the Cho/Cr ratios. In contrast, in both the lithium-treated and valproate-treated patients this decrease was not seen; this attenuation in the change in Cho/Cr ratio changes was statistically significant. It should be noted that Cho/Cr ratios were significantly higher at baseline in the controls compared to both groups of patients, which may have influenced the results. CONCLUSIONS: These findings are the first to examine the effects of dextro-amphetamine on brain choline concentrations. They show that while in controls dextro-amphetamine decreases choline concentrations, lithium and valproate both appear to protect against this effect in bipolar patients. However, as brain ratios were measured rather than the absolute concentration of choline, and these ratios were lowered in patients at baseline, these results must be regarded as preliminary and require replication in future studies.     

Prenatal Exposure to Phthalic Acid Induces Increased Blood Pressure,Oxidative Stress,and Markers of Endothelial Dysfunction in Rat Offspring

Previous studies have reported the harmful effects of exposure to phthalic acid (PA) on heart. No studies have reported the effects of prenatal PA exposure on the structure or function of heart. The current study aimed to investigate the effects of prenatal PA exposure on the markers of oxidative stress and cardiac structure in rats’ offspring. Twenty-four pregnant rats were randomly categorized into three groups of control, exposed to 2.5 and 5 % PA. The morphometric properties of coronary arteries, markers of oxidative stress, and NOS activity were measured in offspring rats. By a dose-dependent manner, the body weight (BW), heart weight (HW), and HW/BW of the intervention groups were reduced and their heart rate and blood pressure were conversely increased compared to the control group. Also, the wall thickness, cross-sectional area of the aorta and septal branch of the descending left coronary artery were significantly increased in the intervention group. In addition, PA significantly increased the level of malondialdehyde and decreased the level of superoxide dismutase and glutathione peroxidase, compared to the control group. This study revealed that prenatal exposure of rats to PA causes vascular dysfunction, increasing oxidative stress, and reduction in cardiac nitric oxide synthetase activity among offspring rats.     

Are DXA/aBMD and QCT/FEA Stiffness and Strength Estimates Sensitive to Sex and Age?

Dual X-ray absorptiometry (DXA) measures areal bone mineral density (aBMD) by simplifying a complex 3D bone structure to a 2D projection and is not equally effective for explaining fracture strength in women and men. Unlike DXA, subject-specific quantitative computed tomography-based finite element analysis (QCT/FEA) estimates fracture strength using 3D bone mineral distribution and geometry. By using experimentally-measured femoral stiffness and strength from a one hundred sample cadaveric cohort that included variations in sex and age, we wanted to determine if QCT/FEA estimates were able to better predict the experimental variations than DXA/aBMD. For each femur, DXA/aBMD was assessed and a QCT/FEA model was developed to estimate femoral stiffness and strength. Then, the femur was mechanically tested to fracture in a sideways fall on the hip position to measure stiffness and strength. DXA/aBMD and QCT/FEA estimates were compared for their sensitivity to sex and age with multivariate statistical analyses. When comparing the measured data with DXA/aBMD predictions, both age and sex were significant (p ≤ 0.0398) for both femoral stiffness and strength. However, QCT/FEA predictions of stiffness and strength showed sex was insignificant (p ≥ 0.23). Age was still significant (p ≤ 0.0072). These results indicate that QCT/FEA, unlike DXA/aBMD, accounted for bone differences due to sex.     

Abdominal cocoon (sclerosing encapsulating peritonitis): a rare cause of intestinal obstruction

A 24 years old lady presented with classical history of acute intestinal obstruction. There was a background history of chronic abdomen for 9 years. There was asymmetrical abdominal distension. On laparotomy, the entire small intestine was cocooned and enclosed in a yellowish white thick fibrotic membrane resulting in obstruction of the small intestine. When the membrane was carefully peeled off the small intestine, the underlying small gut was found to be absolutely healthy. The histopathology report was consistent with non-specific dense fibrosis. Based on these findings, a diagnosis of abdominal cocoon or sclerosing encapsulating peritonitis was made which is an extremely rare cause of small bowel obstruction.