The metabolic disposition of an orally active pyridyl thiadiazinone cardiotonic agent (MPTD) in rat and baboon

1. Oral absorption and bioavailability of the orally active cardiotonic agent, (6RS)-6-methyl-5-(pyrid-4-yl)-3H,6H-1,3,4-[6-14C]thiadiaz in-2-one (MPTD) (5 mg/kg), in rat and baboon were high. Peak blood concentrations of MPTD and total radioactivity were reached by 1.5-4 h when MPTD accounted for 60-70% of total radioactivity. In both species, elimination of MPTD from blood was rapid (t 1/2 = 3-4 h), although total nonspecific radioactivity was eliminated more slowly. 2. Radioactivity was rapidly eliminated by both species mainly into urine. In rat, about 3% dose was collected as 14CO2 and 2% remained in the carcass after 4 days. Recovery from baboon was incomplete (78-86%). 3. Examination of urine indicated extensive metabolism of MPTD showing a marked species difference. In baboon, MPTD was metabolized largely by glucuronidation at the pyridyl nitrogen to yield a quaternary ammonium conjugate and only about 1% of the dose was excreted unchanged. In rat, the major urinary component was unchanged MPTD and no glucuronide conjugate was found. Both species formed the pyridine N-oxide of MPTD as well as a number of unidentified minor components. 4. Distribution of radioactivity in rat was rapid and extensive. In general, elimination from tissues was also rapid, although radioactivity was eliminated much more slowly from the nasal and bronchiolar epithelium and from the preputial gland.     

Influence of a brief aerobic training program on heart rate and subjective response to a psychologic stressor

An experiment was conducted to determine whether a brief program of aerobic exercise would reduce the heart rate and subjective responses of high- and low-fit subjects to a psychologic stressor. Thirty-four high-fit and 34 low-fit subjects were exposed to a moderate stressor (recall of digits backwards test) while their heart rates and subjective responses were monitored. Approximately half of the high- and low-fit subjects then participated in a 13-week aerobic exercise training program, whereas the other subjects did not. After the 13-week period, the subjects were again exposed to the stressor. Results indicated that a) in the pretest the low-fit subjects showed a greater heart rate response to the stressor than the high-fit subjects, b) the training program was effective for increasing subjects' levels of aerobic fitness, and c) the training program was effective for reducing the heart rate response to the stressor of low-fit subjects. These findings provide support for the relationship between fitness and the response to psychologic stressors and they suggest that aerobic training may be an effective way of helping low-fit persons deal with psychologic stressors.     

Inhibition of platelet aggregation by novel triphenylethylene analogs

The present study has evaluated the effect of some newly synthesized triphenylethylene (TPE) analogs on platelet arachidonic acid metabolism and function. All compounds tested inhibited arachidonic acid induced platelet aggregation and several were superior to aspirin in their relative potency. Introduction of a carboxyl function into the alpha-ring, which should enhance binding according to proposed structural models for cyclooxygenase inhibitors, was not found to be beneficial. Increased structural rigidity, which resulted from covalent linkage of two aromatic rings in this series, did not eliminate anti-aggregatory properties.     

Nonreflux complications of hiatal hernia

Patients with massive incarcerated hiatal hernia and no appreciable esophagitis present with a distinctly different clinical picture from those with hiatal hernia and reflux peptic esophagitis. In a recent review, 17 patients were encountered with this problem. The patients were often elderly and presented with the following grave complications: upper gastrointestinal obstruction; upper gastrointestinal bleeding, both acute and chronic, from gastric ulcerations; and perforated gastric ulcerations. In these patients, the surgical approach is better accomplished through the abdominal route. These patients should be distinguished from those with a shortened esophagus resulting from chronic reflux peptic esophagitis who often require thoracotomy for surgical correction.     

Influence of aerobic exercise training and relaxation training on physical and psychologic health following stressful life events

An experiment was conducted to determine whether aerobic exercise training or relaxation training would be effective for reducing the deleterious effects of life stress on physical and psychologic health. Over 1000 college students were surveyed, and 55 of those who reported experiencing a high number of negative life events over the preceding year were assigned to an aerobic exercise training condition, a relaxation training condition, or a no-treatment control condition. Physical and psychologic health were assessed with self-report measures before, halfway through, immediately following, and 8 weeks after the 11-week training (and control) period. Heart rate data collected during a treadmill test indicated that the aerobic exercise training was effective for improving cardiovascular fitness. Psychologic measures indicated that the exercise training condition was more effective than the other two conditions for reducing depression during the first 5 weeks of training. No differences were found among the conditions on self-report measures of physical health. These findings suggest that aerobic exercise training may be useful for reducing the severity and duration of depressive reactions following stressful life change.     

Men’s pathways to risky sexual behavior: Role of co-occurring childhood sexual abuse,posttraumatic stress disorder,and depression histories

Recent reports of sexually transmitted infection-rate increases among men indicate the need for renewed study of male sexual risk behavior to aid development of updated and novel risk reduction interventions. Men who have childhood sexual abuse (CSA) histories consistently report frequent sexual risk behavior. The objective of this sturdy is to explore whether posttraumatic stress disorder (PTSD) and depression are moderators and/or mediators of the association between CSA and sexual risk in adult men. A cross-sectional survey study employing random digit dial recruitment was administered to men aged 18–49 years from Philadelphia County. Two bundred ninety eight men were recruited and screened for CSA history, administered items from the Posttraumatic Stress Diagnostic Scale (PDS) and Center for Epidemiologic Studies—Depression (CES-D), and asked to estimate their number of lifetime sexual partners (LSPs). Effects of sociodemographic characteristics, CSA, PTSD, and depression on the number of LSPs were modeled using Poisson regression. Results show that 197 (66%) men participated; 43 (22%) had CSA histories. CSA was significantly associated with PTSD/depression (P=.03). Four sociodemographic variables (age, race, sexual identity, and education), CSA (incidence rate ratio, IRR=1.47, P<.001), PTSD (IRR=1.19, P=.04), depression (IRR=1.29, P=.001), all 2-way interactions, and the 3-way CSA/PTSD/depression interaction (IRR=11.00, P<.001) were associated with the number of LSPs (R²=0.27). In conclusion, sexual partnership patterns unique to men with CSA histories and comorbid PTSD/depression appear to lead to substantially higher numbers of LSPs. Estimates of this relationship may have been biased toward the null by underreporting that can occur with phone surveys. Cross-sectional studies do not support causal inferences; however, the identification of a moderating and mediating influence of PTSD/depression on the relationship between CSA and sexual risk behavior is important and suggests the need for future studies with larger samples that examine trajectories for CSA, psychiatric illness, and sexual partnerships.     

Human T Lymphocytes Require Lipid as Either Lipoprotein or Nonesterified Fatty Acid for In Vitro Activation

Serum, which is required for activation of T cells in vitro, was fractionated to isolate and identify major supportive components. The serum activity concentrated exclusively with the lipoprotein fractions LDL and HDL. Furthermore, oleic and linoleic acids were equally active supplements, suggesting that resting T cells may require exogenous lipid because they are incapable of synthesizing fatty acid. A survey of fatty acids disclosed that all were capable of some degree of support. Titration delineated the narrow concentration range of lipid supplements successful in supporting T cell proliferation and demonstrated that concentrations must be rigidly controlled to optimize cell proliferation.     

Transmission of STIs/HIV at the partnership level: Beyond individual-level analyses

Mathematical modeling of transmission dynamics of sexually transmitted infections (STIs) and HIV has considerably advanced HIV research by highlighting the importance of certain types of partnerships in epidemic spread. Notably, concurrent partnerships, defined as a sexual partnership in which one or more of the partnership members have other sexual partners while continuing sexual activity with the original partner, have been shown to play a fundamental role in potentiating the spread of STIs and HIV. Risk behaviors such as concurrency and sex without condoms as well as STI/HIV prevalence vary with physical, social, and emotional factors within partnerships. The efficiency of STI/HIV transmission appears to vary across types of concurrent partnerships according to the differing dynamics within them. Previous research on partnership dynamics has improved our understanding of the multidimensional aspects of sexual partnering, but little is understood of how these aspects of sexual partnering interact and increase risks for HIV, nor how types of partnerships, partnership dynamics, and concurrency work together to affect both the behavior of condom use and the biological transmission of disease. In this article, we discuss the need to extend our understanding of concurrency to include partnerships among men who have sex with men (MSM) and to differentiate between types of partnerships and to develop interventions to modify risk within partnerships. We also introduce a conceptual framework that reflects how individual and partner characteristics influence partnership dynamics that in turn influence risk behaviors, such as concurrency and not using condoms, and associated risks for STIs and HIV.