Acute Regulation of Cardiac Metabolism by the Hexosamine Biosynthesis Pathway and Protein O-GlcNAcylation

OBJECTIVE: The hexosamine biosynthesis pathway (HBP) flux and protein O-linked N-acetyl-glucosamine (O-GlcNAc) levels have been implicated in mediating the adverse effects of diabetes in the cardiovascular system. Activation of these pathways with glucosamine has been shown to mimic some of the diabetes-induced functional and structural changes in the heart; however, the effect on cardiac metabolism is not known. Therefore, the primary goal of this study was to determine the effects of glucosamine on cardiac substrate utilization. METHODS: Isolated rat hearts were perfused with glucosamine (0-10 mM) to increase HBP flux under normoxic conditions. Metabolic fluxes were determined by (13)C-NMR isotopomer analysis; UDP-GlcNAc a precursor of O-GlcNAc synthesis was assessed by HPLC and immunoblot analysis was used to determine O-GlcNAc levels, phospho- and total levels of AMPK and ACC, and membrane levels of FAT/CD36. RESULTS: Glucosamine caused a dose dependent increase in both UDP-GlcNAc and O-GlcNAc levels, which was associated with a significant increase in palmitate oxidation with a concomitant decrease in lactate and pyruvate oxidation. There was no effect of glucosamine on AMPK or ACC phosphorylation; however, membrane levels of the fatty acid transport protein FAT/CD36 were increased and preliminary studies suggest that FAT/CD36 is a potential target for O-GlcNAcylation. CONCLUSION/INTERPRETATION: These data demonstrate that acute modulation of HBP and protein O-GlcNAcylation in the heart stimulates fatty acid oxidation, possibly by increasing plasma membrane levels of FAT/CD36, raising the intriguing possibility that the HBP and O-GlcNAc turnover represent a novel, glucose dependent mechanism for regulating cardiac metabolism

Efficiency of primary saliva secretion: an analysis of parameter dependence in dynamic single-cell and acinus models, with application to aquaporin knockout studies

Secretion from the salivary glands is driven by osmosis following the establishment of osmotic gradients between the lumen, the cell and the interstitium by active ion transport. We consider a dynamic model of osmotically driven primary saliva secretion and use singular perturbation approaches and scaling assumptions to reduce the model. Our analysis shows that isosmotic secretion is the most efficient secretion regime and that this holds for single isolated cells and for multiple cells assembled into an acinus. For typical parameter variations, we rule out any significant synergistic effect on total water secretion of an acinar arrangement of cells about a single shared lumen. Conditions for the attainment of isosmotic secretion are considered, and we derive an expression for how the concentration gradient between the interstitium and the lumen scales with water- and chloride-transport parameters. Aquaporin knockout studies are interpreted in the context of our analysis and further investigated using simulations of transport efficiency with different membrane water permeabilities. We conclude that recent claims that aquaporin knockout studies can be interpreted as evidence against a simple osmotic mechanism are not supported by our work. Many of the results that we obtain are independent of specific transporter details, and our analysis can be easily extended to apply to models that use other proposed ionic mechanisms of saliva secretion

Diaphragmatic palsy

Diaphragmatic palsy or paralysis (DP) due to phrenic nerve injury is a rare respiratory condition which may be life-threatening in newborn and young children (Affatato et al. 1988; Haller et al. 1979; de Leeuw et al. 1999). This entity was first described in 1906 in an adult (Stauffer 1979). In newborn patients in the middle of the last century, it was most often due to birth trauma. In the days of advanced neonatal and cardiac surgery, DP is mostly a complication of thoracic surgery (Greene et al. 1975; Schwartz and Filler 1978; Stauffer and Rickham 1972; Stone et al. 1987; Zhao et al. 1985). The incidence is described between 0.3 and 12.8 % and can be unilateral or bilateral (de Leeuw et al. 1999; Schwartz and Filler 1978; Kunovsky et al. 1993; van Onna et al. 1998). DP due to inflammation, neuropathic or idiopathic is rarely seen in this age group

Childhood Sexual Abuse and Health Risk Behaviors in Patients with HIV and a History of Injection Drug Use

Childhood sexual abuse (CSA) is related to poorer health outcomes, associated with increased risk for HIV acquisition, and prevalent among HIV risk groups. Links between CSA and health behavior are an important health concern. We examined the relationship between CSA and transmission risk behavior and medication adherence in 119 HIV-infected individuals with an injection drug use history. 47% reported CSA, with no gender difference. Individuals who experienced CSA were more likely to report sexual HIV transmission risk behavior in the past 6 months, more sexual partners, use of heroin in the past 30 days, and worse adherence to HIV medication than those who did not. These findings confirm that rates of CSA are high in this population, and suggest that a history of CSA may place people managing both HIV and opioid dependence at increased risk for HIV transmission, poor adherence to medication, and vulnerability to substance use relapse

A Comparison by Sexual Orientation of Sexual Health and Sexual Behaviors Among Hispanic Men

BACKGROUND/SIGNIFICANCE: High rates of HIV infection and other sexually transmitted infections (STIs) related to high risk sexual behaviors are a public health problem in the U.S. Hispanics have the second highest rates of HIV infection among racial/ethnic minorities. Previous research with Hispanic men has identified a number of factors that influence sexual risk and render Hispanic men at risk for HIV/STIs. These factors vary by sexual orientation. Despite these differences in sexual risk by sexual orientation, no study to date has compared the sexual behaviors of Hispanic men by sexual orientation. OBJECTIVE: The purpose of this study was to compare the sexual behaviors of a sample of Hispanic men by sexual orientation. METHOD: A descriptive, cross-sectional design was used to collect data from 163 Hispanic men in South Florida, 80 heterosexual and 83 MSM. Participants completed measures of sexual health, sexual behaviors, and demographics. RESULTS: No statistically significant differences were found between the two groups of men in terms of age of sexual debut, number of sexual partners during the previous 3 months, condom usage during the previous 3 months, HIV testing history, and substance use during sex. Statistically significant differences were found between the two groups of men in terms of certain STIs. IMPLICATIONS: Hispanic men as a population may engage in high risk sexual behaviors that place them at risk for HIV/STIs. More research is needed to develop both culturally tailored and sexual orientation appropriate interventions to assist Hispanic men reduce high risk sexual behaviors