No abstract

No abstract

From January 1991 through September 1994, we observed people who were infected with HIV to assess the impact of enteric parasite-associated diarrhea. Respondents answered comprehensive questionnaires covering clinical and epidemiologic information and provided stool specimens monthly, which were examined unstained as well as stained with trichrome, chromotrope 2R, and with Kinyoun carbol-fuchsin, and with indirect immunofluorescence for Cryptosporidium. In all, 602 participants, who were interviewed, provided stool specimens at 3254 monthly visits. Parasites were associated with 50 of 354 (14.1%) acute diarrheal episodes (lasting < or = 28 days) and with 97 of 279 (34.8%) chronic episodes (lasting > 28 days). A parasite was associated with 31 of 222 (14.0%) episodes that occurred when CD4+ counts were > or = 200 cells/microl and with 150 of 566 (26.5%) episodes that occurred when CD4+ counts were < 200 cells/microl. The most commonly identified parasite was C. parvum, which was associated with 18 of 354 (5.1%) acute episodes and 36 (12.9%) of the 279 chronic episodes of diarrhea. In this patient population, enteric protozoan parasites were commonly associated with illness, particularly as immunosuppression worsened, and were more likely to be associated with chronic rather than acute diarrhea.

A positive relationship between income and child outcomes has been observed in data from numerous countries. A key question concerns the extent to which this association represents a causal relationship as opposed to unobserved heterogeneity. We use data from the National Longitudinal Survey of Children and Youth to implement a series of empirical strategies for estimating the existence and size of the effect of income on behavioural-emotional outcomes. We also examine the role of parenting style. Our results indicate that there is little evidence of an effect of income on behavioural-emotional scores. The exclusion of parenting style from the models was found to not bias the estimated income effect, but parenting style was found to have a consistent impact on child outcomes.

No abstract

Background Biobehavioural research methodology can be invasive and burdensome for participants—particularly adolescents with mental illnesses. Human biological researchers should consider how methodological impositions may hinder adolescent research participation. However, literature on adolescent’s voices and concerns toward biobehavioural research participation is virtually non-existent. Aim This study was designed to determine adolescents’ perceptions of participation in research involving the collection of biomarkers via blood, saliva and/or urine samples. Subjects and methods Urban adolescent females (aged 12–19) receiving outpatient mental health treatment (n = 37) participated in focus groups with concurrent survey administration to explore attitudes, beliefs and willingness/intentions toward biobehavioural research participation. Results Participants had favourable attitudes toward biobehavioural research and were amenable to provide each specimen type. Mistrust for research emerged, however, and concerns related to privacy and confidentiality were expressed. Conclusion Participant recruitment is a critical component in study design and implementation; this includes knowledge of population-specific recruitment barriers and facilitators. This innovative paper provides a context for the research participants’ decision-making process, strategies to allay fears and concerns and concrete areas to target in research-related interventions. Although the findings are from a specific, US-based sample, the implications warrant replication of the research in other geosocial settings.

The purpose of this study was to investigate the effects of angiotensin II and bradykinin on intracellular Ca2+ dynamics in cultured endothelial cells. We used the "second-generation" fluorescent Ca2+ indicator fura-2, in conjunction with dual-wavelength fluorescence spectroscopy, in cultured adherent pulmonary arterial endothelial cells. Angiotensin II (up to 2 microM) had no consistent effect on intracellular Ca2+ levels. In contrast, bradykinin (10 nM) elicited a transient increase of cytosolic free Ca2+, from the resting value of 37 +/- 5 to 647 +/- 123 nM, followed by a decline to a steady-state value of 113 +/- 14 nM, which was significantly higher than the resting Ca2+ levels. Bradykinin's Ca-stimulatory effect was dose dependent, having a half-maximally effective concentration of approximately 1 nM and a maximally effective concentration of 10 nM. A B1-receptor agonist, Des-Arg9-bradykinin, was much less effective than bradykinin as modulator of cytosolic Ca2+. Moreover, a B1-receptor antagonist, Des-Arg9, [Leu8]-bradykinin, did not significantly affect the increase of cytosolic Ca2+ elicited by bradykinin. On the other hand, the bradykinin-elicited increase of Ca2+ was almost completely inhibited by a novel B2-receptor antagonist, D-Arg-[Hyp3, Thi5,8, D-Phe7]-bradykinin. Bradykinin increased cytosolic free Ca2+ levels in cells maintained in Ca2+-deficient extracellular medium, suggesting that the peptide mobilized Ca2+ from intracellular stores. However, the absence of extra-cellular Ca2+ resulted in an 80-90% attenuation of the transient Ca2+ response, whereas the posttransient steady-state response was completely absent. These findings are consistent with the notion that the bradykinin-elicited transient Ca2+ response is dependent on both extra- and intracellular Ca2+ and that the posttransient steady-state response is entirely dependent on extracellular Ca2+. Endothelial cells were responsive to a second dose of bradykinin after a 10-min interim period of incubation in the absence of the peptide hormone. The absence of extracellular Ca2+ during the interim period, or the pretreatment of cells with ionomycin in the absence of extracellular Ca2+, prevented the response of the cells to a second dose of bradykinin. Bradykinin- or ionomycin-desensitized cells could be resensitized by a brief incubation period in Ca2+-replete medium. The results are consistent with the notions that cellular resensitization requires the replenishment of intracellular Ca2+ and that bradykinin, but not angiotensin II, modulates intracellular Ca2+ dynamics in endothelial cells by interacting with a B2-type receptor.

The nonapeptide bradykinin is an important growth factor for many cancers. Certain peptide and non-peptide bradykinin antagonists show remarkable anti-cancer activities in both in vitro and in vivo cancer models, especially of lung and prostate cancers. Bradykinin antagonists stimulate apoptosis in cancers by a novel "biased agonist" mechanism: they block intracellular increase of calcium concentration but stimulate the MAP kinase pathway. This unbalanced effect stimulates caspase activation. In nude mouse xenotransplants of lung and prostate cancers the antagonists inhibit angiogenesis and activation of membrane metalloproteases (MMP 2 and 9). In the xenotransplants certain bradykinin antagonists showed higher potency than standard anti-cancer drugs, without evident toxicity to the hosts. These compounds offer great promise for development of new anti-cancer drugs.