3-Dimensional morphometric analysis of murine bladder development and dysmorphogenesis

Background : Disorders of the urinary tract represent a major cause of morbidity and impaired quality of life. To better understand the morphological events responsible for normal urinary tract development, we performed 3‐D reconstructive analysis of developing mouse bladders in control, mgb?/?, and Fgfr2^Mes?/? mice. Results : Detrusor smooth muscle differentiation initiated in the bladder dome and progressed caudally with the leading edge extending down the right posterior surface of the bladder. Gender‐specific differences in detrusor smooth muscle development were observed during early embryonic development. Bladder trigone morphology transitioned from an isosceles to equilateral triangle during development due to the preferential lengthening of the urethra to ureter distance. The primary defect observed in mgb?/? bladders was a significant reduction in detrusor smooth muscle differentiation throughout development. Deviations from normal trigone morphology correlated best with VUR development in Fgfr2^Mes?/? mice, while alterations in intravesicular tunnel length did not. Conclusions : Multivariate morphometric analysis provides a powerful tool to quantify and assess urinary tract development. Developmental Dynamics 241:522–533, 2012. © 2012 Wiley Periodicals, Inc.     

Determinants of cockroach and mouse exposure and associations with asthma in families and elderly individuals living in New York City public housing.

BACKGROUND: Asthma prevalence is high in the inner city, and morbidity has been associated with cockroach and mouse allergens. OBJECTIVE: To characterize the relationships among pests, allergens, pesticides, and asthma in New York City public housing. METHODS: In 324 apartments, dust samples collected from beds and kitchens were analyzed for cockroach (Bla g 2) and mouse (mouse urinary protein [MUP]) allergens, pest populations were monitored, and residents were interviewed about home characteristics and asthma symptoms. RESULTS: Cockroaches were found in 77% of the apartments, and evidence of mice was found in 13%. Allergens and pesticide use were associated with pest infestation, and 15% of residents reported using illegal pesticides. The percentage of apartments with high allergen levels varied significantly by building (Bla g 2: P = .002; MUP: P = .03), as did the percentage of apartments with cockroaches (P = .002) and daily mouse sightings (P = .02). Thirty-seven percent of the apartments had at least 1 resident with physician-diagnosed asthma. In family buildings, apartments with high Bla g 2 levels had 1.7 times greater odds of having an asthmatic resident (95% confidence interval, 1.2-2.3). In senior citizen buildings, apartments with high MUP levels had 6.6 times greater odds of having an asthmatic resident (95% confidence interval, 1.4-31.7), controlling for smoking and other potential confounders. CONCLUSIONS: Previous studies have identified home characteristics associated with the presence of cockroaches and mice, but the present findings suggest that building-level characteristics can affect high pest exposure. Furthermore, the high asthma prevalence in residents and the use of illegal pesticides highlight the need for safe and effective building-wide pest control strategies.     

Nitric oxide in glutamate-induced compound action potential threshold shifts

OBJECTIVE: Investigate the role of NO as a neurotransmitter in the gerbil cochlea and the effects of (7-NI) on compound action potential (CAP) threshold elevations induced by l-glutamate, an agonist at the NMDA glutamate receptor subtype, to further elucidate the role of NO in cochlear excitotoxicity. METHOD: In anesthetized gerbils, CAP thresholds were recorded before and after cochlear perfusions with a control solution of artificial perilymph (APS) and a test solution of L-glutamate (GA) in three experimental groups. RESULTS: The control group showed no CAP threshold elevations (p<0.05) when APS was perfused after systemic pre-treatment with 7-NI. GA perfusion alone caused significant elevation (p<0.05) of the mean cochlear CAP threshold (25 dB SPL+/-5.8 dB to 78 dB SPL+/-19.5 dB). The CAP threshold elevation was prevented (p<0.05) when the animals were pretreated with 7-NI before GA perfusion (24 dB SPL+/-4.2dB to 27 dB SPL+/-6.7 dB). CONCLUSION: NO mediates excitotoxicity when the cochlea is perfused with L-glutamate.     

6-(4-chlorophenyl)-3-substituted-thieno[3,2-d]pyrimidin-4(3H)-one-based melanin-concentrating hormone receptor 1 antagonist

Genetic manipulation studies in mice at both the MCH receptor 1 (MCHR1) as well as the MCH peptide levels have implicated MCHR1 as a key player in energy homeostasis. The phenotype exhibited by these studies, that is, increased metabolic rate, resistance to high fat diet, and subsequent weight loss, has spurred considerable efforts to develop antagonists of MCHR1. In continuation of efforts directed toward this goal, the present work capitalizes on the putative binding mode of an MCH antagonist, resulting in the identification of several novel chemotypes that are potent and selective MCHR1 antagonists. In addition, the favorable pharmacokinetics of representative examples has allowed for the evaluation of an MCHR1 antagonist in a high fat diet-induced obese rodent model of obesity. The tolerability of the right-hand side of the template for diverse chemotypes accompanied by favorable effects on weight loss enhances the attractiveness of this template in the pursuit toward development of effective anti-obesity agents.     

Chronic lung injury in preterm lambs: abnormalities of the pulmonary circulation and lung fluid balance

Chronic lung disease of early infancy, or bronchopulmonary dysplasia, is a frequent complication of prolonged mechanical ventilation after premature birth. Pulmonary hypertension and edema are common features of this condition, which is often attributed to long-term, repetitive overinflation of incompletely developed lungs. The overall objective of this work was to examine the effects on the pulmonary circulation and lung fluid balance of different ventilation strategies using large versus small inflation volumes in an animal model of bronchopulmonary dysplasia. We studied 16 newborn lambs that were delivered prematurely (124+/-3 d gestation, term = 147 d) by cesarean section and mechanically ventilated for 3 to 4 wk. Ten lambs were ventilated at 20 breaths/min, yielding a tidal volume of 15+/-5 mL/kg, and six lambs were ventilated at 60 breaths/min, yielding a tidal volume of 6+/-2 mL/kg. All lambs received surfactant at birth and had subsequent surgery for closure of the ductus arteriosus and catheter placement to allow serial measurements of pulmonary vascular resistance and lung lymph flow. Chronic lung injury, documented by serial chest radiographs and postmortem pathologic examination, developed in all lambs irrespective of the pattern of assisted ventilation. Pulmonary vascular resistance, which normally decreases during the month after birth at term, did not change significantly from the first to the last week of study. Lung lymph flow, an index of net transvascular fluid filtration, increased with time in lambs that were ventilated at 20 breaths/min, but not in lambs ventilated at 60 breaths/min. Lymph protein concentration decreased with time, indicative of increased fluid filtration pressure, without evidence of a change in lung vascular protein permeability. Postmortem studies showed interstitial lung edema, increased pulmonary arteriolar smooth muscle and elastin, decreased numbers of small pulmonary arteries and veins, and decreased capillary surface density in distal lung of chronically ventilated lambs compared with control lambs that were killed either 1 d (same postconceptional age) or 3 wk (same postnatal age) after birth at term. Thus, chronic lung injury from prolonged mechanical ventilation after premature birth inhibits the normal postnatal decrease in pulmonary vascular resistance and leads to lung edema from increased fluid filtration pressure. These abnormalities of the pulmonary circulation may contribute to the abnormal respiratory gas exchange that often exists in infants with bronchopulmonary dysplasia.     

A test of the maternal stress theory of human male homosexuality

Both the neurohormonal theory of sexual orientation and previous research on humans and animals suggest that male homosexuality may arise from prenatal stress during the brain's sexual differentiation. Stress-proneness and retrospective reports of stress during pregnancy were obtained from mothers of male and female heterosexuals, bisexuals, and homosexuals. Each mother also rated pregnancy stress for a heterosexual sibling of the subject. For males, neither between-family nor within-family analyses revealed a maternal stress effect for either sexual orientation or childhood gender nonconformity. However, mothers of effeminate children reported more stress-proneness than other mothers. Male homosexuality nevertheless was strongly familial, suggesting a reconsideration of genetic and familial environmental mechanisms.     

Optimization of metabolic activation for four mutagens in a bacterial, fungal and two mammalian cell mutagenesis assays

The optimum concentrations of Aroclor-induced rat liver S9 microsomal fraction for the mutagenic activity of the four standard mutagens 2-aminofluorene (2-AF), acriflavine (ACR), benzo[a]pyrene (BP) and cyclophosphamide (CP) were determined in four mutation assays. The four assays were the Ames test using Salmonella typhimurium strain TA100, cycloheximide resistance in the yeast Saccharomyces cerevisiae, the mouse lymphoma TK assay and the human peripheral lymphocyte cytogenetic assay. BP was the only mutagen to be most active at comparable S9 concentrations, of approximately 1%, for all four assays. The optimum S9 concentrations for each of the remaining three mutagens varied substantially between the four assays. ACR was a potent direct-acting mutagen in both mammalian cell assays. The mouse lymphoma TK assay results showed similar optimal values of 1.5% S9 or below for each of the four test agents. The assay with the largest variation of optimal S9 values for the four mutagens was the Ames test in strain TA100, although it also had the widest peaks of activity over the range of S9 concentrations tested. It is likely that the diversity of findings is due to a variety of metabolites affecting the different genetic endpoints that are measured in these assays. Thus from these results it is not possible for bacterial optimization data to be related to other routine in vitro systems. The use of more than one concentration of S9 would contribute useful information.     

Sodium chlorite administration in Long-Evans rats: reproductive and endocrine effects

Long-Evans rats, 4-6 weeks of age, were given access to 0, 1, 10, or 100 ppm sodium chlorite in deionized water ad libitum as drinking water. Males were exposed 56 days, and females for 14 days prior to breeding and throughout the 10-day breeding period. Males were evaluated for sperm parameters and reproductive tract histopathology following the breeding period. Females were exposed throughout gestation and lactation. Dams and pups were necropsied at weaning. Decreases in serum T3 and T4 were observed on Postnatal Days 21 and 40 in male and female pups exposed to 100 ppm chlorite or above. Additionally, groups of males were exposed to 0, 10, 100, or 500 ppm ad libitum in the drinking water to confirm observed subtle reproductive effects and examine dose-effect relationships. A significant increase in the percentage of abnormal sperm morphology (P less than 0.001) and decrease in sperm direct progressive movement (P less than 0.01) were observed for adult males at chlorite levels of 100 or 500 ppm. Since other clinical and reproductive endpoints were not affected, sperm morphology and sperm direct progressive movement may be two of the more sensitive indicators of reproductive damage.     

Trends in maternal and child health care: implications for research and issues for social work practice

Trends are reviewed in four areas of maternal and child health care: (1) prenatal care; (2) infant mortality; (3) teenage pregnancy; and (4) HIV infected mothers and infants. The purpose of this review is to identify major trends in these programmatic areas, key indicators of physical-social health risk and survival, and central issues relevant to research and social work practice. Attention is directed to the status of research, and the usefulness of existing data sets available to researchers in the four programmatic areas of maternal and child health care under review. Emphasis is given to the importance of the integration of theory, research findings, and practice.     

Serotoninergic and noradrenergic projections to the ventral posterolateral nucleus of the monkey thalamus

In the present study, serotoninergic and noradrenergic varicosities were identified in the ventral posterolateral nucleus of the macaque monkey. Monoaminergic neurons projecting to the ventral posterolateral nucleus of the thalamus were identified by using retrograde labeling with horseradish peroxidase combined with immunocytochemical staining for serotonin or dopamine-beta-hydroxylase. The midbrain nucleus raphe dorsalis was the major site of origin for neurons providing a serotoninergic projection to the ventral posterolateral nucleus. A few retrogradely labeled serotonin-containing neurons were also observed in the central superior and the raphe pontis nuclei. Noradrenergic cells with projections to the thalamus were primarily located in the nucleus locus coeruleus with some projection neurons in the nucleus subcoeruleus, and the A5 catecholamine cell group of the pons.