Dietary cholesterol and oxidised cholesterol: effects on sperm characteristics,antioxidant status and hormonal profile in rats

Present study was designed to compare the potential effects of high serum levels of LDL and oxidised LDL (OxLDL) on spermatogenesis parameters in male Wistar rats. Animals were allocated into three groups and were fed for 14 weeks with normal, cholesterol‐rich and oxidised cholesterol‐rich diets. Blood lipid profile, sex hormones level, as well as sex organs weight were evaluated. The sex organs weight in oxidised cholesterol‐fed group was significantly reduced (P < 0.05). Spermatozoa count in the group with high serum concentration of OxLDL (64 ± 4.2 × 10⁶) was markedly lower (P < 0.01) than that of normal rats (87 ± 4.1 × 10⁶) and rats with high serum level of LDL (90 ± 6.3 × 10⁶). Similarly, the percentage of viable spermatozoa was significantly (P < 0.001) decreased from 78% to 52% by high level of OxLDL in serum. While, nonoxidised LDL did not have suppressive effects on spermatogenesis and organs weight. Consistent with these effects, the serum concentration of sex hormones including FSH (P < 0.001), LH (P < 0.001) and testosterone (P < 0.01) was significantly decreased only in rats with high level of OxLDL but not in rats with high level of nonoxidised LDL. In conclusion, high OxLDL level showed higher destructive effect on reproductive system compared to the high LDL level.     

Tacrolimus ameliorates functional disturbances and oxidative stress in isoproterenol-induced myocardial infarction

Background

The inflammatory responses play a major role in the pathogenesis of acute myocardial infarction (MI). Early inhibition of inflammation may improve post MI cardiac function. The aim of this study was to investigate the effects of tacrolimus on cardiac function, hemodynamic parameters as well as histopathologic and electrocardiographic changes in isoproterenol-induced myocardial infarction.

Methods

Male Wistar rats were randomly divided into six groups of control, isoproterenol alone, tacrolimus alone, and isoproterenol plus tacrolimus (0.5, 1 and 2 mg/kg). Isoproterenol (100 mg/kg) was injected subcutaneously for two consecutive days to induce myocardial infarction, and simultaneously tacrolimus was administered orally twice a day for three days.

Results and conclusions

Administration of isoproterenol resulted in myocardial edema and necrosis as well as a marked reduction in the left ventricular systolic pressure (LVSP), left ventricular contractility (LVdP/dt_max) and relaxation (LVdP/dt_min) along with a severe elevation in left ventricular end-diastolic pressure (LVEDP). Isoproterenol also elevated the ST-segment and suppressed the R-amplitude and R-R interval on ECG. It was found that all doses of tacrolimus could amend the ECG pattern and ameliorated the isoproterenol induced disturbances in cardiac function. Acute and short term treatment with tacrolimus at dose of 2 mg/kg significantly (P < 0.001) improved LVdP/dt_max from 2712 ± 82 in myocardial infarcted rats to 4592 ± 149 mmHg/sec. Similarly, tacrolimus lowered LVEDP from 17.6 ± 0.68 in MI group to the value of 5.6 ± 0.22 mmHg (P < 0.001). Furthermore, tacrolimus was found to reduce malondialdehyde concentration in serum and myocardium by 50-70% (P < 0.001).The results of this study showed that acute treatment with tacrolimus, coincided with the occurrence of myocardial infarction, strongly protected the myocardium against the isoproterenol-induced myocardial infarction; where this might be due to the anti-inflammatory properties of tacrolimus.     

Maternal healthcare needs assessment survey at Rabia Balkhi Hospital in Kabul, Afghanistan

OBJECTIVE: Since the Department of Health and Human Services chose Rabia Balkhi Hospital (RBH) in Kabul, Afghanistan, as a site for intervention in 2002, the status of women's health there has been of interest. This study created a tool to assess accessibility and quality of care of women admitted from May to July, 2005. METHODS: A 39-item questionnaire was created in English and translated into Dari. Hospital staff administered the survey to 292 women admitted to RBH for obstetric and gynecological complaints. RESULTS: Approximately 40% of the women traveled between 1 and 5 hours to reach RBH. Only 54% (158/292) of women reported having their blood pressure monitored during their pregnancy. About one-third of women reported that they had never received an immunization. CONCLUSIONS: This survey tool ascertained that women who received care at RBH traveled great lengths to reach the facility. Preventative measures such as blood pressure checks and immunizations are areas that need improvement.     

Negative Association of Plasma Levels of Vitamin D and miR-378 With Viral Load in Patients With Chronic Hepatitis B Infection

Background:

Chronic Hepatitis B (CHB) is accompanied by inflammation of liver because of infection with Hepatitis B Virus (HBV). Previous studies revealed an inverse association between vitamin D and HBV DNA levels.

Objectives:

The current study aimed to investigate the levels of 25 (OH) D3 (the steady form of vitamin D), miR-378 and HBV DNA in the patients with CHB.

Patients and Methods:

One hundred and seventy three patients with HBeAg negative CHB were recruited for the study. Plasma levels of HBVDNA and 25 (OH) D3 were quantified. The expression level of miR-378 in plasma was measured by a relative quantitative Real Time Polymerase Chain Reaction (qRT-PCR) assay.

Results:

In the pathway regression analysis, the plasma level of 25 (OH) D3 showed a significant inverse correlation with plasma levels of HBV DNA (-0.198, P = 0.008) and direct correlation with miR-378 (0.188, P = 0.013). Similarly plasma level of miR-378 had inverse association with HBV DNA level (-0.177, P = 0.020).

Conclusions:

These results suggest that vitamin D could involve in a miRNA- mediated regulatory pathway in control of HBV replication. Further studies are recommended to understand the effects of miR-378 and anti-infective action of vitamin D on Hepatitis B Virus.     

Simple Enucleation Versus Radical Nephrectomy in the Treatment of pT1a and pT1b Renal Cell Carcinoma

Background

Simple tumor enucleation (TE) showed excellent oncologic results in large retrospective series. No study has compared oncologic outcomes after TE and radical nephrectomy (RN) for the treatment of pT1 renal cell carcinoma (RCC). The aim of the present study is to compare the oncologic outcomes after TE and RN in pT1 RCCs.

Methods

We retrospectively analyzed 475 patients who underwent TE or RN for pT1 RCC, N0, M0, between 1995 and 2007. TE was performed in 332 patients and RN in 143. Local recurrence, progression-free survival (PFS), and cancer-specific survival (CSS) were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions, and differences were assessed with the log rank statistic. Univariate and multivariate Cox regression models were also used.

Results

The 5- and 10-year PFS estimates were 91.3 and 88.7% after RN and 95.3 and 92.8% after TE (P?=?NS), respectively. The 5- and 10-year CSS estimates were 92.1 and 89.4% after RN and 94.4% (5- and 10-year CSS) after TE (P?=?NS), respectively. No statistically significant differences between RN and TE were found after adjusting CSS probabilities according to age at surgery, grade, stage, or clear cell subtype. Surgical treatment was not a predictor of PFS or CSS by both univariate and multivariate analyses. The potential limitation of this study is that the data originate from a retrospective review.

Conclusions

TE can achieve oncologic results similar to those of RN for the treatment of pT1 RCCs, provided tumors are carefully selected on the basis of their safe and complete removal.     

The effect of sublingual isosorbide dinitrate on acute urinary retention due to benign prostatic hyperplasia

Acute urinary retention (AUR) is one of the most important long-term compli-cations of benign prostatic hyperplasia (BPH). Nitric oxide (NO) as a transmitter can relax smooth muscles of the bladder neck and external sphincter. Several studies have reported that sublingual isosorbide dinitrate (ISDN), as a NO donor, can lead to significant decrease in resting pressure of the external sphincter, and its rapid onset of action may be useful in the treatment of AUR. This study was designed to asses the effect of ISDN on AUR in patients with BPH. In this clinical trial, 60 men with BPH-induced AUR were randomly selected via a simple sampling method. Participants were randomly divided into case and control groups. Patients in the case group received 200 mg of sublingual ISDN and participants in the control group received placebo. After 20 min, participants were asked to void spontaneously and the urine was collected in scale containers. Following this, urethral catheterization was done on all the participants and the residual urine was measured. Data were analyzed using SPSS version 15. There was no signi-ficant difference in the mean age of the two groups (P-value = 0.28). The mean voided urine volume in the case group was 201 mL and, in the control group, it was 18 mL (P = 0.004). About 30% in the case group and 3.3% in the control group could void spontaneously after receiving ISDN or placebo (P = 0.006). In the case group, there was a significant correlation between voided urine volume and total urine volume in the bladder (P = 0.03) and in the size of the prostate (P = 0.001). Our study shows that ISDN can be effective in the treatment of BPH-induced AUR with decrease in bladder outlet resistance. ISDN is more effective in younger men and in those with smaller prostates.     

Neutral and acidic human tracheobronchial mucin

Human bronchial mucin from a patient suffering from chronic bronchitis was solubilized in aqueous solution containing sodium azide and protease inhibitors and purified by Sepharose 4B and 2B column chromatography. The mucin was further purified by cesium bromide density gradient centrifugation. Sodium dodecyl sulfate-polyacrylamide gel (7.5%) electrophoresis of this material showed high-molecular-weight mucin component(s) at the top of the gel. Chemical analysis of this preparation indicated a typical mucin profile of amino acids and carbohydrates. Ion-exchange chromatography resulted in resolution of the purified mucin into neutral and acidic fractions. Comparison of the chemical composition of these two fractions showed higher mole percentage of threonine, serine, sialic acid, and sulfate in the acidic fraction. Chemical deglycosylation of the purified mucin preparation with trifluoromethane sulfonic acid was carried out at 20°C for 3 1/2 h. Sialic acid, fucose, galactose, and W-acetylglucosamine were completely removed, whereas traces ofN- acetylgalactosamine were still detected. High-pressure liquid chromatography of the deglycosylated products from native, neutral, and acidic mucin preparations resulted in a principal peptide, P₁, with identical amino acid composition. Cyanogen bromide (CNBr) treatment of the peptide P₁ from neutral and acidic mucins and subsequent fractionation of the fragments by high-pressure liquid chromatography resulted in similar peptide profiles. The P₁ peptide fraction was further subjected to high-pressure liquid chromatography in a second solvent system, which resulted in two peaks, P_1a and P_1b. Gel filtration of both peptides in 6 M guanidine hydrochloride indicated a single peak with molecular weight of approximately 97 kDa. The amino acid profile of the two peptides was dominated by high levels of threonine, serine, and proline, which combined accounted for nearly 39% of the total residues, and in most respects, the profile resembled that of native mucin. End-group analysis of the peptide P_1a indicated a blocked N-terminus, whereas serine was found to be the N-terminal amino acid in the peptide P_1b. Rabbit antibodies prepared against the peptide P₁ from native tracheal mucin reacted strongly with neutral and acidic mucin as well as the mucin from human colon. Both neutral and acidic human tracheal mucins were immunologically reactive with mouse monoclonal antibody HMPFG-2, which was prepared against human mammary mucin. However, the response of this antibody to human colonic mucin was rather weak.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or Department of Defense.     

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

BackgroundMerosin‐deficient congenital muscular dystrophy type 1A (MDC1A) is occurred by mutations in LAMA2 gene that encodes the laminin α2 chain (merosin). MDC1A is a predominant subtype of congenital muscular dystrophy. Herein, we identified two missense mutations in LAMA2 gene in compound heterozygous status in an Iranian patient with MDC1A using whole‐exome sequencing (WES).MethodsIn the present study, we evaluated genetic alterations in an Iranian 35‐month‐old boy with MDC1A and his healthy family using WES method. The identified mutations further confirmed by Sanger sequencing method. Finally, in silico analysis was conducted to further evaluation of molecular function of the identified genetic variants.ResultsWe identified two potentially pathogenic missense mutations in compound heterozygous state (c.7681G>A p.Gly2561Ser and c.4840A>G p.Asn1614Asp) in LAMA2 gene as contributing to the MDC1A phenotype. The healthy parents of our proband are single heterozygous for identified mutations. These variants were found to be pathogenic by in silico analysis.ConclusionsIn general, we successfully identified LAMA2 gene mutations in an Iranian patient with MDC1A using WES. The identified mutations in LAMA2 gene can be useful in genetic counseling, prenatal diagnosis, and predicting prognosis of MDC1A.