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ABSTRACT: Black sexual minority men (BSMM) experience the worst HIV treatment outcomes in the United States. Drug use increases HIV transmission risks and reduces health care engagement. Perceived health care provider stigma and medical mistrust minimizes treatment efforts. This study identified nursing and health care preferences among drug-using BSMM. In-depth qualitative interviews were conducted among 30 BSMM who reported drug use in Baltimore City, MD, from December 2018 to March 2019. Analysis identified themes as client preferences for nursing practices and gaps in clinical services. Participants' ages ranged from 23 to 63 years (M = 41.1). Most (91%) reported living with HIV. The following themes were identified as nursing and health care preferences: (a) being genuine, (b) knowing drug treatment and social services, (c) understanding drug use effects, (d) providing mental health services, and (e) clarifying treatment recommendations. Nurses and health care facilities can improve cultural competency for drug-using BSMM. Future research should identify the impact of these preferences on HIV care outcomes among BSMM.

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While research investigates the role and influence of geo-social networking (GSN) applications on HIV, less is known about the impact of GSN functions on disease transmission. In our formative research on young Black men who have sex with men's (YBMSM) technology use patterns and preferences for a smartphone-based HIV prevention intervention, we found that study participants used GSN "block" and "filter" functions as protective mechanisms against racism and racial sexual discrimination. Yet, we suggest that these functions may unintentionally create restrictive sexual networks that likely increase their risk for disease transmission. As such, we contend that attention to the unintended effects of these protective mechanisms against racism on GSN applications is fundamentally a public health issue that requires more research and explicit intervention. Ultimately, we use this work to hypothesize the role of blocking and filtering as a strategy to avoid racism on GSN applications that may partly explain HIV disparities among YBMSM.

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Biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), represent new opportunities to reduce critically high HIV infection rates among young black men who have sex with men (YBMSM). We report results of 24 dyadic qualitative interviews (N=48), conducted in Los Angeles, CA, exploring how YBMSM and their friends view PrEP and PEP. Interviews were analyzed using a grounded theory approach. Participants had widely divergent levels of knowledge about these prevention methods. Misconceptions and mistrust regarding PrEP were common, and concerns were expressed about PrEP-related stigma and the potential for gossip among peers who might assume a person on PrEP was HIV-positive. Yet participants also framed PrEP and PEP as valuable new options within an expanded "tool kit" of HIV prevention strategies that created possibilities for preventing new HIV infections, dating men with a different HIV status, and decreased anxiety about exposure to HIV. We organized themes around four main areas: (1) information and misinformation about biomedical HIV prevention; (2) expectations about PrEP, sexual behavior, and stigma; (3) gossip, disclosure, and "spreading the word" about PrEP and PEP; and (4) the roles of PrEP and PEP in an expanded HIV prevention tool kit. The findings suggest a need for guidance in navigating the increasingly complex array of HIV-prevention options available to YBMSM. Such "prevention navigation" could counter misconceptions and address barriers, such as stigma and mistrust, while helping YBMSM make informed selections from among expanded HIV prevention options.

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The purpose of this study was to determine the regional distribution of blood flow deficit in the skeletal muscle vascular bed of rats with a chronic myocardial infarction (MI) and heart failure (HF). Accordingly, blood flow was determined (via radioactive microspheres) in rats with a small infarction (MI less than 30%) and in rats with a large (MI greater than 30%) infarction, induced by surgically ligating the left main coronary artery, and compared with rats that had received a sham operation. Results demonstrate that blood flow to the hindlimb musculature was significantly (P less than 0.05) less during a given level of treadmill exercise (20% grade and speed of 28 m/min) in the MI groups of rats compared with their sham counterparts. These differences in hindlimb blood flow were the result of blood flow deficits found in the individual muscles of the thigh and leg. Moreover, the blood flow deficits were more pronounced in the MI greater than 30% group of rats compared with the MI less than 30% group. The blood flow deficits found for the MI greater than 30% group of rats were positively correlated with the percentage of fast-twitch oxidative-glycolytic fibers and negatively correlated with the percentage of fast-twitch glycolytic fibers found in the individual muscles. Our study supports the contention that MI rats demonstrate skeletal muscle blood flow abnormalities during exercise. It appears that the degree of blood flow abnormalities produced in rats is dependent on the size of the MI and the amount of left ventricular dysfunction produced in the HF state.

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The regional blood flow response (via radioactive microspheres) was determined for female rats after 6 wk of high-intensity sprint training (HIST) or limited cage activity as the animals exercised at work loads that would elicit maximal O2 uptake. Blood flow to the different organs of the abdominal region was greatly reduced during maximal exercise conditions, and the magnitude of the reduction appeared to be similar for both the HIST group of rats and their sedentary (SED) control counterparts. Of the 20 different hindlimb muscles examined in the present study, blood flow to the soleus, plantaris, gastrocnemius, flexor hallicus longus, vastus lateralis, rectus femoris, biceps femoris, and adductor magnus and brevis muscles was significantly greater (P less than 0.05) in the HIST rats during maximal exercise conditions than in the SED control rats. Correspondingly, blood flow to the total hindlimb during maximal exercise was also significantly greater in the HIST rats than in the SED control rats [240 +/- 18 vs. 192 +/- 15 (SE) ml.min-1.100 g-1]. These results support the contention that the increase in maximal cardiac output that is produced by HIST in the rat is primarily directed toward the working skeletal muscle and not toward the organs found in the abdominal region. We conclude from these experiments that HIST will produce significant adaptations in central cardiac function and skeletal muscle blood flow in the rat.

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The influence of enzymic distribution on lidocaine metabolism was investigated in the once-through perfused rat liver preparation. Low input concentrations of 14C-lidocaine (1-2 microM) and preformed monoethylglycine xylidide (MEGX; 2.3-2.8 microM) were delivered by normal and retrograde flow directions to the liver preparations at 10 ml/min per liver. Upon reversal of normal to retrograde delivery of lidocaine, the rates at which lidocaine, MEGX, and glycine xylidide (GX) left the liver almost doubled, whereas the rates of appearance of (total) hydroxylated lidocaine and MEGX in bile and perfusate increased to lesser extents. Upon reversal of normal to retrograde delivery of preformed MEGX, the rates of appearance of MEGX and GX were virtually unchanged. Computer simulations on lidocaine and preformed MEGX metabolism were performed on both evenly distributed ("parallel tube" model) and enzyme-distributed systems. An even or parallel distribution of N-deethylation and hydroxylation activities for lidocaine metabolism failed to predict the observed increased hepatic availability of lidocaine. Rather, the distribution of a low-affinity, high-capacity N-deethylation system anterior to a high-affinity, low-capacity hydroxylation system for lidocaine metabolism adequately predicted the increased hepatic availability of lidocaine. Further extension of these consistent enzyme-distributed models on the metabolism of lidocaine metabolites suggests that the N-deethylation and hydroxylation activities for the metabolism of lidocaine, MEGX, 3-hydroxyidocaine, and 3-hydroxy MEGX are not identically distributed. When these enzyme-distributed models were appraised with reference to the "parallel tube" and "well-stirred" models of hepatic drug clearance, predictions from these enzyme-distributed models proved to be superior to the "parallel tube" and "well-stirred" models for the present data on lidocaine metabolites with normal and retrograde perfusions. Previously published data on lidocaine and MEGX metabolism after inputting 4 micrograms/ml (17 microM) lidocaine at flow rates of 10, 12, 14, and 16 ml/min were reexamined with respect to the adequacy of these enzyme-distributed models. They were found to be superior to the evenly-distributed or "parallel tube" model in predicting hepatic availability of lidocaine and the rate of appearance of MEGX. However, the enzyme-distributed systems were not as consistent as the "well-stirred" model in predicting lidocaine hepatic availability in these flow experiments.

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The kinetics of sulfation of 3H-acetaminophen (preformed metabolite) and 14C-acetaminophen (generated metabolite) during the parallel incubations of tracer concentrations of 3H-acetaminophen and 14C-phenacetin in (a) isolated rat hepatocytes and (b) rat 9000g supernatant fractions from liver and from isolated hepatocytes were compared to results obtained from rat liver perfusion studies (Pang and Gillette, J. Pharmacol. Exp. Ther. 207, 178-194, 1978; Pang and Terrell, J. Pharmacol. Exp. Ther. 216, 339-346, 1981). The isolated rat hepatocytes and the subcellular fractions represent in vitro systems whose metabolic activities are apparently homogeneous and contrast the in situ rat liver perfusion system where differential distribution of drug metabolizing activities exists within the rigid architecture of the intact organ. The ratio of sulfation (intrinsic clearance = 23.8 ml/min/liver) to O-deethylation (intrinsic clearance = 11.7 ml/min/liver) activities within these isolated hepatocytes (2.2-2.7) and subcellular fractions (3.72) were similar, but were reversed in the perfused liver preparation (0.2-0.5) depending on the model of hepatic drug clearance used for the calculation. Moreover, the sulfation to O-deethylation activity in the isolated rat hepatocyte system was independent of cell concentration (3.8 to 11 X 10(8) cells/ml) or the method of isolation of hepatocytes (by normal digestion or retrograde digestion). The reason for the reversal of lower O-deethylation activity in the subcellular and cellular systems remains unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

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Enalaprilat (MK-422), a new and potent angiotensin- converting enzyme inhibitor, and its monoethyl ester precursor, enalapril, were studied in a single pass perfused rat liver preparation under constant perfusate flow (10 ml/min) at concentrations of 0.29-0.41 microM for 14C-enalapril and 0.01-0.015 microM for 3H- enalaprilat . During their simultaneous delivery to the same rat liver preparation, the steady state hepatic extraction ratio of 14C-enalapril was high (0.861 +/- 0.02) and 14C- enalaprilat appeared rapidly in effluent perfusate plasma. Of the enalapril dose, 22.7 +/- 6.9% appeared in bile. 14C- Enalaprilat accounted for 79% of the total radioactivity in bile (18% of dose) whereas 14C-enalapril was present only as 10% of the total (2.3% of dose). By contrast, the steady state hepatic extraction of 3H- enalaprilat was very low (0.053) and the disappearance was virtually identical to the appearance of 3H- enalaprilat in bile. These findings suggest that diffusional barrier exists for enalaprilat as the preformed metabolite, which hinders penetration into hepatocytes, and therefore, elimination. The precursor, enalapril, effectively brings enalaprilat into hepatocytes were more extensive biliary excretion of the generated metabolite takes place. This account adds to our further understanding of metabolite kinetics; in addition to the uneven distribution of enzyme system and the intrinsic clearance for metabolite formation and elimination, the presence of a diffusional barrier is another important determinant which may cause deviations between the kinetics of a generated and performed metabolite.

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The elimination of [14C]acetaminophen which was formed from [14C]phenacetin was slower than that for the preformed metabolite, [3H]acetaminophen. The observation had been attributed to the uneven distribution of enzyme systems for O-deethylation in the formation of acetaminophen and sulfate-conjugation of acetaminophen in the liver parenchyma. In this study, retrograde perfusion which reversed not only the direction of hepatic flow into the liver but also the location of enzyme systems with respect to the flow path, was used to examine the elimination kinetics of [14C]acetaminophen and [3H]acetaminophen. In the same rat liver preparation, both [14C[phenacetin and [3H]acetaminophen in tracer concentrations were delivered simultaneously into the perfused rat liver in situ preparation with normal directional flow (into the portal vein and out of the hepatic vein). The direction of flow was then reversed to retrograde perfusion (into the hepatic vein and out of the portal vein) which was later reverted back to normal perfusion. The elimination of [14C]acetaminophen was again slower than the elimination of [3H]acetaminophen during normal perfusion, but the elimination kinetics were virtually identical for both metabolite species during retrograde perfusion. This finding confirmed our previous hypothesis that sulfate-conjugation occurred predominantly in the periportal region while O-deethylation occurred preferentially in the centrilobular region of the liver and showed that retrograde perfusion was a useful probe in the investigation of the uneven distribution of hepatic drug metabolizing enzyme systems.

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