FAS-670 A/G and FAS-1377 G/A polymorphism in cell death pathway gene FAS and human male infertility

ObjectiveTo study the role and association of functional variations present in FAS gene with idiopathic male infertility.MethodsThe case-control study comprised of two groups: 160 idiopathic infertile nonobstructive azoospermia patients and 200 fertile healthy control men. Genotyping for single-nucleotide polymorphism of FAS-670 A/G (rs1800682) and FAS-1377 G/A (rs2234767) was done by PCR-RFLP method. DNA sequencing was used to ascertain PCR-RFLP results. For FAS-670 A/G and FAS-1377 G/A functional polymorphism, allele and genotype distribution were evaluated using Chi-square test.ResultsAllele and genotype distribution did not differ significantly between patients and controls for FAS-670 A/G and FAS-1377 G/A.ConclusionsHuman male infertility is a complex disorder and thus other genetic or environmental factors may be contributing to the complex etiology.     

Cholestasis and growth in neonates with gastroschisis

PurposeThe aim of this study was to determine the incidence of cholestasis and the correlation between cholestasis and weight-for-age z scores in parenteral nutrition–dependent neonates with gastroschisis.MethodsA single-center retrospective review of 59 infants born with gastroschisis from January 2000 to June 2007 was conducted. Demographic and clinical data were collected and analyzed. Subjects were divided into cholestatic and noncholestatic groups. Statistical analyses included the Student t test, Wilcoxon rank sum test, Fisher exact test, and a general linear model.ResultsFifty-nine neonates with gastroschisis were identified, and 16 (28%) of 58 patients developed cholestasis. Younger gestational age and cholestasis were found to be independently associated with weight-for-age z score in 30 of 58 patients with available long-term follow-up data.ConclusionsParenteral nutrition–dependent neonates with gastroschisis remain at considerable risk for the development of cholestasis. Both gestational age and cholestasis were found to be independent risk factors, predisposing these neonates to poor postnatal growth.     

CD4+CD25+ regulatory T cells protect against injury in an innate murine model of chronic kidney disease

Studies of mechanisms of disease regulation by CD4+CD25+ regulatory T cells (Treg) have been focused on their interaction with effector T cells; however, the possibility that regulation might involve noncognate cells has not been explored in detail. This study investigated the effect of CD4+CD25+ Treg on macrophage proinflammatory properties and phenotype in vitro and found that they modulate macrophages by inhibiting their activation, leading to reduced proinflammatory cytokine production and a downregulated effector phenotype. For testing the in vivo significance of this effect, CD4+CD25+ T cells that expressed high levels of Foxp3 were reconstituted into SCID mice after induction of Adriamycin nephropathy, a noncognate model of chronic renal disease. CD4+CD25+ T cells significantly reduced glomerular and interstitial injury. In addition, there was a significant fall in the number of macrophages in both the glomeruli and interstitium of SCID mice that were reconstituted with Treg as compared with the Adriamycin alone group. Blockade of TGF-beta using neutralizing antibodies significantly impaired the protective effect of Treg. These findings delineate a TGF-beta-dependent Treg-macrophage inhibitory interaction that can explain cognate-independent protection by Treg.     

Risk factors for the development and progression of carcinoid heart disease

The development of valvular heart disease in patients with carcinoid syndrome is thought to be related to the secretion of vasoactive substances by a tumor. We sought to identify modifiable risk factors for the development of carcinoid heart disease because this may help define strategies to attenuate the disease process. Two hundred fifty-two patients with carcinoid syndrome were prospectively followed with serial echocardiograms at 6-month intervals. Clinical characteristics, biochemical markers, and radiologic markers were measured at set intervals. An echocardiographic scoring system was applied. Patients were defined as having progression of carcinoid heart disease if the echocardiographic score increased by ≥25%. After a median follow-up of 29 months, 44 patients developed carcinoid heart disease or had progression of existing valvular dysfunction. At time of progression of carcinoid heart disease compared to the previous 6 months, there was a significant increase in median levels of 5-hydroxyindoleacetic acid (5-HIAA; 791 vs 460.5 μmol/24 hours) and flushing episodes (4.5 vs 2 episodes per day). Independent predictors of the development or progression of carcinoid heart disease were a 5-HIAA level ≥ 300 μmol/24 hours and ≥ 3 episodes of flushing per day. 5-HIAA levels of ≥ 300 to 599, 600 to 899, and > 900 μmol/24 hours conferred 2.74, 3.16, and 3.40 times the risk of progression of carcinoid heart disease, respectively. In conclusion, a 5-HIAA level ≥ 300 μmol/24 hours and ≥ 3 flushing episodes per day are predictors of the development or progression of carcinoid heart disease.     

Long-term psychosocial adjustments, satisfaction related to gender and the family equations in disorders of sexual differentiation with male sex assignment

Purpose  

The varied management and counseling in disorders of sexual differentiation (DSD) depends a lot on the socioeconomic structure. A follow-up study was designed to evaluate the outcome in terms of patient satisfaction with strong socio-cultural issues.     

Study of the extent of ocular absorption of acetazolamide from a developed niosomal formulation, by microdialysis sampling of aqueous humor

Acetazolamide, a carbonic anhydrase inhibitor is used orally (no topical formulation being available in the market) for the reduction of intraocular pressure (IOP) in patients suffering from glaucoma. Two major reasons responsible for the failure to develop a topically effective formulation of acetazolamide are its low solubility (0.7mg/ml) and its low permeability coefficient. It is generally recognized that topical acetazolamide formulation possessing efficacy similar to that achieved upon oral administration would be a significant advancement in the treatment of glaucoma. In order to enhance the bioavailability of acetazolamide by topical route and to improve the corneal permeability of the drug, the niosomes of acetazolamide were prepared (by reverse phase evaporation method) and coated with Carbopol for the latter's bioadhesive effect. The pharmacodynamic studies showed 33% fall in IOP with the developed formulation, and the effect was sustained for 6h after instillation. The effect compared well with a four times higher concentration of dorzolamide (Dorzox, a topical CAI available in the market. In the present study, the aqueous humor disposition of the drug from the developed bioadhesive coated niosomal formulation (ACZREVbio) is compared with the aqueous suspension of the drug (containing 1% (w/v) Tween 80 as a dispersing agent) at similar concentrations. The concentration of acetazolamide absorbed in the aqueous humor at various times from the control suspension and from ACZREVbio was determined by microdialysis in male albino rabbits. Microdialysis provides a complete concentration versus time profile and hence is an important advance to the regional sampling of tissues. The peak concentration of drug absorbed in the aqueous humor from the ACZREVbio formulation (14.94microg/ml) was almost two times of that obtained with the equivalent amount of acetazolamide control suspension (6.93microg). The results show a significant broadening of peak from 80 to 120min with the concentration of more than 13microg being maintained at these times, for the bioadhesive coated niosomal formulation (ACZREVbio). An important observation was the fact that a high drug concentration of 12.02microg reached immediately, i.e., 20min after instillation of ACZREVbio indicating a high penetration being achieved, while a meagre concentration of only 3.53microg is obtained at 60min after instillation of the control suspension. The aqueous humor disposition indicates peaks and troughs in drug concentration which may be related to the decrease in aqueous humor formation, such that the drug concentration/volume increased at these points.     

Evaluation of BBL CHROMagar VanRE for Detection of Vancomycin-Resistant Enterococci in Rectal Swab Specimens

A study was performed on 517 surveillance rectal swabs to evaluate a selective and differential chromogenic medium, the BBL CHROMagar VanRE (CVRE), which enables recovery and identification of VanA- and VanB-containing Enterococcus faecium (ENFM) and Enterococcus faecalis (ENFS) isolates. Compared to BBL Enterococcosel agar, a bile-esculin-azide-vancomycin (BEAV) agar, the initial overall sensitivity, specificity, and positive and negative predictive values of CVRE for the detection of vancomycin-resistant ENFM and ENFS were 99.1% and 94.8% and 84.2% and 99.7%, respectively. Among our patient population, more vancomycin-resistant enterococci (VRE) were recovered with CVRE than BEAV.Vancomycin-resistant enterococci (VRE) are major causes of nosocomial infections in health care facilities, and those patients infected with VRE have worse outcomes while hospitalized (8). Rapid, reliable identification of these antibiotic-resistant organisms is crucial for patient management and infection control measures (9, 12).Culture from rectal swabs or stool specimens onto bile-esculin-azide agar with vancomycin (BEAV) is the VRE screening method used in many clinical laboratories. Confirmation of VRE using this medium requires 48 to 72 h. Chromogenic agars to detect VRE demonstrate promise (1-7, 10). BBL CHROMagar VanRE (CVRE; BD Diagnostics, Sparks, MD) is a selective and differential chromogenic agar under development for the detection of vancomycin-resistant E. faecium (VRENFM) and vancomycin-resistant Enterococcus faecalis (VRENFS). CVRE contains 8 μg/ml of vancomycin and uses chromogenic substrates to phenotypically differentiate VRENFM as mauve colonies and VRENFS as green colonies. Other bacteria are inhibited or typically grow as a color other than mauve or green. Our study compared the clinical performance of CVRE with that of BEAV for primary isolation and detection of VRE from surveillance rectal swabs.