Preclinical evaluation for noninvasive reversal following long-term vas occlusion with styrene maleic anhydride in langur monkeys

A preclinical evaluation for reversal through a noninvasive approach following long-term vas occlusion with styrene maleic anhydride (SMA) has been attempted in langur monkeys at the level of semen parameters, sperm functional tests, semen biochemistry, histology and ultrastructure of reproductive organs, hematology and serum clinical biochemistry including antisperm antibodies (ASA), prostate-specific antigen (PSA) and testosterone. Noninvasive reversal through palpation, percutaneous squeezing and electrical stimulation, forced vibratory movements and suprapubic percussion in the inguinal segments and per-rectal digital massage was attempted in seven langur monkeys after 540 days following vas occlusion. The results revealed instant azoospermia reversal on the same day of reversal with impaired sperm quality, which showed gradual improvement and normospermia with normal motility and viability after 60-90 days of reversal. Sperm functional tests, including ultrastructure of spermatozoa, indicative of sterility in the initial ejaculations, reached normalcy after 90-120 days of reversal. The seminal plasma biochemistry indicative of obstructive azoospermia regained a normal pattern after 90-120 days of reversal. The morphology of testes that showed focal degeneration during 540 days of vas occlusion and that of vasa deferentia that showed exfoliation of epithelial cells resumed to normal morphology comparable with control animals after 150 days of reversal. The morphology of the epididymis, seminal vesicle and prostate did not show appreciable changes following vas occlusion and after noninvasive reversal compared with those of control animals. Hematology, serum clinical chemistry, ASA, PSA and testosterone fluctuated within control limits, indicating safety of the procedure at the level of accessory reproductive organs. The results suggest that noninvasive reversal is feasible even after long-term vas occlusion with SMA and is safe without adverse side effects.     

Safety evaluation of long-term vas occlusion with styrene maleic anhydride and its non-invasive reversal on accessory reproductive organs in langurs

Aim: To evaluate the safety of the long term vas occlusion with styrene maleic anhydride (SMA) and its non-invasive reversal at the level of accessory reproductive glands (ARGs) in langurs. Methods: The morphology of seminal vesicle and ventral prostate was evaluated by light as well as transmission electron microscopy. Serum clinical chemistry and urine albumin were evaluated in an autoanalyzer using reagent kits. Fructose, acid phosphatase and zinc in the seminal plasma were evaluated spectrophotometrically according to the WHO manual. Serum testosterone,prostate specific antigen and sperm antibodies were evaluated by enzyme-linked immunosorbent assays (ELISA) using reagent kits and hematology was estimated according to standard procedures. Results: The morphological features and secretory activity of the seminal vesicle and prostate were normal as evidenced by the presence of well-developed mitochondria, rough endoplasmic reticulum, Golgi bodies, secretory granules and normal nuclear characteristics throughout the course of investigation. Serum testosterone and prostate specific antigen remained unaltered and serum antisperm antibodies level presented negative titres. Urine albumin was nil. Total red blood corpuscles (RBC), white blood corpuscles (WBC), hemoglobin (Hb) and red cell indices, serum protein, glucose, cholesterol,creatinine, creatine kinase (CK), serum glutamate oxalate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), lactate dehydrogenase (LDH), bilirubin, urea, triglycerides and high-density lipoprotein (HDL) did not show appreciable changes following vas occlusion and after its non-invasive reversal. Although fructose, acid phosphatase (ACP) and zinc in the seminal plasma showed a significant reduction following vas occlusion, it could not be related to the morphology of seminal vesicle and prostate. Conclusion: SMA vas occlusion and its non-invasive reversal do not damage the accessory reproductive organs.     

Unusual germ cell organization in the seminiferous epithelium of a murid rodent from southern Asia, the greater bandicoot rat, Bandicota Indica

In the greater bandicoot rat, Bandicota indica, of south-east Asia, nine cell associations were documented in the testicular seminiferous epithelium. In about 10% of the tubule cross sections two or more cell associations occurred and, furthermore, some of the generations of germ cells within the cell associations were sometimes either out of phase, or missing, in the tubule cross sections. These features, together with the fact that this species has a highly pleiomorphic sperm head shape, are somewhat reminiscent of those of the seminiferous epithelium in humans and some other primates but not of common laboratory rodents. This species could thus be a good model for investigating irregular patterns of spermatogenesis in naturally occurring wild species of rodent.     

Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin

Mutations in parkin are largely associated with autosomal recessive juvenile parkinsonism. The underlying mechanism of pathogenesis in parkin-associated Parkinson's disease (PD) is thought to be due to the loss of parkin's E3 ubiquitin ligase activity. A subset of missense and nonsense point mutations in parkin that span the entire gene and represent the numerous inheritance patterns that are associated with parkin-linked PD were investigated for their E3 ligase activity, localization and their ability to bind, ubiquitinate and effect the degradation of two substrates, synphilin-1 and aminoacyl-tRNA synthetase complex cofactor, p38. Parkin mutants vary in their intracellular localization, binding to substrates and enzymatic activity, yet they are ultimately deficient in their ability to degrade substrate. These results suggest that not all parkin mutations result in loss of parkin's E3 ligase activity, but they all appear to manifest as loss-of-function mutants due to defects in solubility, aggregation, enzymatic activity or targeting proteins to the proteasome for degradation.     

A primary care perspective of posttraumatic stress disorder for the Department of Veterans Affairs

Posttraumatic stress disorder (PTSD) is a major mental disorder associated with significant morbidity, psychosocial impairment, and disability. The diagnosis of PTSD can be missed in a primary care setting, as patients frequently present with somatic complaints or depression and are often reluctant to discuss their traumatic experiences. As recent studies of veterans returning from the Gulf War and the Iraqi War suggest high rates of PTSD, the U.S. Department of Veterans Affairs (VA) Hospitals are gearing up to face this challenge. It is important to screen these veterans for symptoms of PTSD and make an appropriate referral if required. In this article, we attempt to review PTSD with a special focus on the VA population. In addition to discussing the epidemiology, diagnosis, and treatment options for PTSD, we also suggest screening questions for both combat-related and military sexual trauma-related PTSD.     

Pain and terminal delirium research in the elderly

This article highlights new developments in assessment and management of pain and delirium.     

Inhibition of nitric oxide synthesis potentiates apoptosis in the rabbit corpus luteum

To determine if nitric oxide (NO) plays a role in corpus luteum (CL) physiology by affecting progesterone secretion or luteal apoptosis, an in-vitro pseudopregnant rabbit ovarian perfusion system was used to measure the effects of an inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME), on progesterone secretion and corpus luteal apoptosis as measured by internucleosomal DNA breakdown. Pseudopregnant rabbit ovaries perfused in vitro with L-NAME did not demonstrate any significant differences compared with control ovaries in progesterone secretion. However, apoptosis, as measured by internucleosomal breakdown, was significantly increased in L-NAME-perfused CL compared with controls. While NO does not appear to directly affect progesterone secretion, there does appear to be a role for NO in CL maintenance, or a role for inhibition of NO production in CL regression.     

Fetal interleukin-1 receptor antagonist gene polymorphism, intra-amniotic interleukin-1beta levels, and history of spontaneous abortion

OBJECTIVE: The purpose of this study was to determine whether fetal carriage of specific alleles of the polymorphic interleukin-1 receptor antagonist gene is associated with variations in intra-amniotic cytokine levels and previous pregnancy outcomes. STUDY DESIGN: Fetal cells in midtrimester amniotic fluid from 189 women were tested for interleukin-1 receptor antagonist intron 2 length polymorphisms. Concentrations of cytokines in amniotic fluid were tested by enzyme-linked immunosorbent assay. Pregnancy history data were obtained subsequently. RESULTS: Homozygosity for interleukin-1 receptor antagonist allele 1 was detected in 13 of 17 fetuses (76.5%) from women whose previous pregnancies all ended in spontaneous abortions, as compared with 33 of 74 fetuses (44.6%) from women with at least 1 previous term birth ( P = .02). Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with only 1 (5.9%) previous spontaneous abortion, as opposed to 31 pregnancies (41.9%) that were associated with a previous term delivery ( P = .004). A similar relationship between interleukin-1 receptor antagonist allele 1 and spontaneous abortions was observed when pregnancies of white women only were analyzed. Median mid trimester amniotic fluid interleukin-1beta concentrations were higher in women whose previous pregnancies ended in term deliveries (15.7 pg/mL), as opposed to women with 1 to 2 (6.4 pg/mL; P = .04) or > or =3 (4.1 pg/mL; P = .007) previous spontaneous abortions. Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with elevated intra-amniotic interleukin-1beta levels (16.2 pg/mL), as compared with interleukin-1 receptor antagonist allele 1 homozygotes (10.8 pg/mL; P = .03). CONCLUSION: Fetal carriage of interleukin-1 receptor antagonist allele 1 is associated with reduced intra-amniotic interleukin-1beta concentrations and an increased occurrence of spontaneous abortions in previous pregnancies.     

Primary cardiac paraganglioma

We report a case of a 29-year-old male, who during workup of hypertension was found to have a malignant primary paraganglioma of the heart. The tumor arose from the site of the aortopulmonary window and right ventricular outflow tract (RVOT) and was removed with the aid of cardiopulmonary bypass. Reconstruction of the RVOT and pulmonary valve was necessary because of involvement by the tumor. The surgical course was uncomplicated, with normalization of catecholamine secretion and blood pressure.