The regulation and consequences of immune-mediated cell death in atheromatous diseases

Atheromatous diseases are lipid and cell-rich vascular disorders that include coronary artery disease (CAD), transplant vascular disease (TVD), and restenosis. Considering the inflammatory nature of these diseases, cytotoxic immune mechanisms such as the FasL and granzyme/perforin pathways most likely play important roles in the development and remodeling of many lesions. Furthermore, although the contributions of immune responses to each disease vary, the correspondent localization of certain mediators and effectors suggests that they may contribute to a spectrum of atheromatous diseases. In this review, the contribution of immune cell-mediated cell death in the onset and pathogenesis of CAD and TVD is examined.     

Determinants of coping responses among Mexican American adolescents

This study examined relationships among perceived stress, self-esteem, acculturation, and gender with the coping response of 472 Mexican American adolescents aged 14 to 16 years. Subjects were drawn from a predominantly Mexican American population located in the Lower Rio Grande Valley region of Texas. Data were collected through a self-report instrument consisting of perceived stress, acculturative status, self-esteem, and coping strategy scales. Subjects reported relatively high perceived stress levels, low acculturation, and moderate self-esteem scores with no significant gender differences. Analysis revealed self-esteem as most predictive of a more effective overall coping response. Results suggest Mexican American adolescents possessing high self-esteem are less likely to encounter damage to their sense of self when confronted with stressors, thus allowing for productive coping.     

Delayed treatment of tuberculosis patients in rural areas of Yogyakarta province,Indonesia

Background  

In year 2000, the entire population in Indonesia was 201 million and 57.6 percent of that was living in rural areas. This paper reports analyses that address to what extent the rural structure influence the way TB patients seek care prior to diagnosis by a DOTS facility.     

Incidence of maternal tachycardia during the second stage of labor: a prospective observational cohort study

Objective: To our knowledge, this is the largest prospective study reporting on maternal heart rate (MHR) levels in laboring women (30 patients), and maternal tachycardia that is a potential risk factor in fetal monitoring confusion. Our objective was to analyze a large population of contiguous laboring patients and to assess the MHR levels attained during the second stage.

Methods: We performed a prospective study that analyzed MHR levels of second-stage laboring patients evaluating numerous predisposing maternal conditions. Univariate and stepwise multivariate logistic regression analysis were performed.

Results: A total of 1105 contiguous patients were analyzed and 33.9% had a sustained MHR ≥100; 18.8% had an MHR ≥110; and 9.1% had an MHR ≥120. Multivariate analysis of all potential predisposing maternal conditions did not reveal any specific variable as uniformly significant for predicting maternal tachycardia across all levels of analysis.

Conclusions: The incidence of maternal tachycardia in the second stage of labor is common. We recommend that if the MHR is ≥100 during labor, the simultaneous maternal and fetal heart rate (FHR) monitoring will be used to minimize the potential for fetal monitoring confusion and risking poor fetal outcome if the fetus is in distress.     

Descriptive analysis of patients with community-onset and hospital-onset methicillin-resistant Staphylococcus aureus infections.

Three hundred sixty-seven hospital- and community-onset methicillin-resistant Staphylococcus aureus (MRSA) infections diagnosed in a Dallas-Fort Worth Metroplex community hospital are described. Differences in age, gender, ethnicity, and susceptibility to four antibiotics between the two groups of patients are explored.     

Cell-autonomous induction of functional tumor suppressor 15-lipoxygenase 2 (15-LOX2) contributes to replicative senescence of human prostate progenitor cells

Normal human prostatic (NHP) epithelial cells undergo senescence in vitro and in vivo, but little is known about the tissue-specific molecular mechanisms. Here we first characterize young primary NHP cells as CK5(+)/CK18(+) intermediate basal cells that also express several other putative stem/progenitor cell markers including p63, CD44, alpha2beta1, and hTERT. When cultured in serum- and androgen-free medium, NHP cells gradually lose the expression of these markers, slow down in proliferation, and enter senescence. Several pieces of evidence implicate 15-lipoxygenase 2 (15-LOX2), a molecule with a restricted tissue expression and most abundantly expressed in adult human prostate, in the replicative senescence of NHP cells. First, the 15-LOX2 promoter activity and the mRNA and protein levels of 15-LOX2 and its multiple splice variants are upregulated in serially passaged NHP cells, which precede replicative senescence and occur in a cell-autonomous manner. Second, all immortalized prostate epithelial cells and prostate cancer cells do not express 15-LOX2. Third, PCa cells stably transfected with 15-LOX2 or 15-LOX2sv-b, a splice variant that does not possess arachidonate-metabolizing activity, show a passage-related senescence-like phenotype. Fourth, infection of early-passage NHP cells with retroviral vectors encoding 15-LOX2 or 15-LOX2sv-b induces partial cell-cycle arrest and big and flat senescence-like phenotype. Finally, 15-LOX2 protein expression in human prostate correlates with age. Together, these data suggest that 15-LOX2 may represent an endogenous prostate senescence gene and its tumor-suppressing functions might be associated with its ability to induce cell senescence.     

In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine

Background

Muscarinic receptor mediated adverse effects, such as sedation and xerostomia, significantly hinder the therapeutic usefulness of first generation antihistamines. Therefore, second and third generation antihistamines which effectively antagonize the H₁ receptor without significant affinity for muscarinic receptors have been developed. However, both in vitro and in vivo experimentation indicates that the third generation antihistamine, desloratadine, antagonizes muscarinic receptors. To fully examine the in vivo antimuscarinic efficacy of desloratadine, two murine and two rat models were utilized. The murine models sought to determine the efficacy of desloratadine to antagonize muscarinic agonist induced salivation, lacrimation, and tremor. Desloratadine's effect on the cardiovascular system was explored in both rodent models.

Results

In the pithed rat, both desloratadine (1.0 mg/kg, i.v.) and the muscarinic M₂ selective antagonist, methoctramine (0.5 mg/kg, i.v.), inhibited negative inotropic (left ventricular dP/dt) effects caused by oxotremorine, a nonselective muscarinic agonist (p < 0.05). Negative chronotropic effects caused by oxotremorine were inhibited by desloratadine, methoctramine, and the muscarinic M₃ selective antagonist, 4-DAMP (1.0 mg/kg, i.v.). A late positive inotropic event observed after the initial decrease was inhibited by all three test compounds with desloratadine and 4-DAMP being the most efficacious. In the conscious animal, inhibition of baroreflex-mediated bradycardia was evaluated. Unlike atropine (0.5 mg/kg, i.v.), desloratadine did not alter this bradycardia. The antimuscarinic action of desloratadine on salivation, lacrimation, and tremor was also explored. In urethane-anesthetized (1.5 g/kg, i.p.) male ICR mice (25–35 g) desloratadine (1.0, 5.0 mg/kg) did not inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, unlike atropine (0.5 mg/kg) and 4-DAMP (1.0 mg/kg). In conscious mice, desloratadine failed to inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, lacrimation, and tremor. However, desloratadine did inhibit oxotremorine-induced tremor in phenylephrine pretreated animals.

Conclusion

The presented data demonstrate that the third generation antihistamine, desloratadine, does not significantly antagonize peripheral muscarinic receptors mediating salivation and lacrimation, therefore, xerostomia and dry eyes should not be observed with therapeutic use of desloratadine. Our data also indicate when administered to a patient with a compromised blood-brain barrier, desloratadine may cause sedation. Patients with compromised cardiovascular systems should be closely monitored when administered desloratadine based on our results that desloratadine has the ability to interfere with normal cardiovascular function mediated by muscarinic receptors.