RESUMO
The use of chlordecone (CLD), a chlorinated polycyclic pesticide used in the French West Indies banana fields between 1972 and 1993, resulted in a long-term pollution of agricultural areas. It has been observed that this persistent organic pollutant (POP) can transfer from contaminated soils to food chain. Indeed, CLD is considered almost fully absorbed after involuntary ingestion of contaminated soil by outdoor reared animals. The aim of this study was to model toxicokinetics (TKs) of CLD in growing pigs using both non-compartmental and nonlinear mixed-effects approaches (NLME). In this study, CLD dissolved in cremophor was intravenously administrated to 7 Creole growing pigs and 7 Large White growing pigs (1 mg kg-1 body weight). Blood samples were collected from time t = 0 to time t = 84 days. CLD concentrations in serum were measured by GCMS/MS. Data obtained were modeled using Monolix (2019R). Results demonstrated that a bicompartmental model best described CLD kinetics in serum. The influence of covariates (breed, initial weight and average daily gain) was simultaneously evaluated and showed that average daily gain is the main covariate explaining inter-individual TKs parameters variability. Body clearance was of 76.7 mL kg-1 d-1 and steady-state volume of distribution was of 6 L kg-1. This modeling approach constitutes the first application of NLME to study CLD TKs in farm animals and will be further used for rearing management practices in contaminated areas.
Assuntos
Clordecona/toxicidade , Inseticidas/toxicidade , Animais , Clordecona/análise , Ingestão de Alimentos , Poluentes Ambientais , Inseticidas/análise , Cinética , Modelos Químicos , Musa , Poluentes do Solo/análise , Suínos , Toxicocinética , Índias OcidentaisRESUMO
Although abundant literature supports the notion that neuropeptide Y (NPY) synergizes in vivo and in vitro, the vasomotor activity elicited by norepinephrine (NE), the converse interaction (i.e., the adrenergic modulation of the NPY vasomotor response) has been less characterized. To assess whether NE synergizes the vasomotor effect of NPY, the rat arterial mesenteric bed was chosen as a model experimental system. Mesenteries were precontracted with NE and few minutes later were perfused with exogenous NPY. Under these conditions, NPY contracted the arterial mesenteric bed with an EC50 value of 0.72 +/- 0.06 nM. NPY was unable to contract this vascular territory without an agonist-induced precontraction. Other agonists, such as endothelin-1, a synthetic analog of prostaglandin F2alpha, or 5-hydroxytryptamine, also were effective primers because in their presence, NPY was a potent vasoconstrictor. In contrast, mesenteries precontracted with KCl failed to evidence the NPY-induced rise in perfusion pressure. Two structural analogs of NPY, PYY and [Leu31, Pro34]NPY, mimicked the activity of NPY. The NPY fragment 13-36 did not elicit such a response. All NPY analogs exhibited less efficacy and potency relative to NPY. The NPY- and related structural analog-induced vasoconstriction was competitively and reversibly antagonized by BIBP 3226; the pA2 of the NPY interaction was 7.0. The application of 0.1 to 1 microM BIBP 3226 or 0.1 to 10 nM prazosin at the peak of the NPY vasomotor response elicited a gradual blockade of the vasoconstriction. Although BIBP 3226 blocked the increase in perfusion pressure elicited by NPY, leaving unaffected the NE-induced tone, 10 nM prazosin blocked the full response, including the NE-induced component. Tissue preincubation with 200 nM nifedipine abolished the NPY-induced vasoconstriction; likewise, the acute application of 10 to 100 nM nifedipine blocked gradually the maximal NPY-induced contraction. Removal of the mesenteric endothelial layer increased the potency of NPY by 2-fold; it also slightly potentiated the antagonist activity of BIBP 3226. The synergism between NPY and NE backs the principle of sympathetic cotransmission.
Assuntos
Arginina/análogos & derivados , Artérias Mesentéricas/fisiologia , Músculo Liso Vascular/fisiologia , Neuropeptídeo Y/análogos & derivados , Neuropeptídeo Y/farmacologia , Norepinefrina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Arginina/farmacologia , Dinoprosta/farmacologia , Sinergismo Farmacológico , Endotelina-1/farmacologia , Endotélio Vascular/fisiologia , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Nifedipino/farmacologia , Fragmentos de Peptídeos/farmacologia , Cloreto de Potássio/farmacologia , Prazosina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Neuropeptídeo Y/antagonistas & inibidores , Serotonina/farmacologia , Vasoconstrição/fisiologiaRESUMO
This article reviews human immunodeficiency virus (HIV) infection in Haiti. The evolution of the epidemic in Haiti, its spread from urban to rural areas, its varied clinical manifestations, and the attitudes of Haitian people toward HIV infection provide important lessons on understanding and managing this infection in a developing country. The heterosexual spread of HIV, particularly among the poor, is well-documented as is the role of other sexually transmitted diseases along with tuberculosis. Coinfection of HIV and tuberculosis have led researchers to study the effects of six-month supervised intermittent tuberculosis therapy both in controlling tuberculosis and slowing the progression of HIV. Various surveys and discussion groups about acquired immunodeficiency virus knowledge and beliefs demonstrate a large deficit in HIV education despite campaigns to educate the population. The great impact of HIV disease on morbidity and mortality in Haiti indicates that a great deal of work still needs to be accomplished and demonstrates the frustration in fighting the infection in countries with inadequate resources and infrastructure. Advances in HIV vaccine research seem to be the most promising option for developing countries such as Haiti.
Assuntos
Infecções por HIV/epidemiologia , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Feminino , Infecções por HIV/diagnóstico , Haiti/epidemiologia , Humanos , Incidência , Masculino , Gravidez , Fatores de Risco , Distribuição por Sexo , Taxa de SobrevidaRESUMO
BACKGROUND AND OBJECTIVES: This article documents the history, politics, and economics that have contributed to a health care delivery crisis in Haiti and why family medicine will be crucial for the recovery of Haiti's health care. Since the United Nations intervention, there has been some improvement in health conditions. However, the embargo and political turmoil left little infrastructure on which to build. Developing family medicine, one of the priorities of the Ministry of Health, will reverse traditional forces that favor emigration and specialization and will provide the country with well-trained physicians who can treat most of the common health problems of Haiti. These common preventable and treatable problems are now contributing to short life expectancy and high infant mortality. While the ultimate responsibility for Haiti's health rests with Haitian health professionals, the country has an immediate need for international humanitarian assistance, particularly for general medical care.
PIP: With its 7 million people inhabiting an area the size of the state of New Jersey and with average annual per capita income of $225, Haiti is the poorest and most densely populated country in the Western Hemisphere. 85% of children in rural Haiti have clinical evidence of malnutrition, the infant mortality rate is 94/1000 live births, the maternal mortality rate is 4.5/1000 live births, life expectancy is 55 years, and there are rapidly growing rates of tuberculosis, malaria, and AIDS. Much of Haiti's health crisis is tied to the country's recent troubled political and economic past. That past has disrupted Haiti's health infrastructure to such an extent that Haitian people routinely suffer with, and often die from, readily preventable and treatable illnesses. Haiti's health care infrastructure cannot be rebuilt without humanitarian support and technical assistance from the international community. The authors explain the history, politics, and economics which have contributed to the health care delivery crisis in Haiti and why family medicine will be crucial for the recovery of the country's health care. The development of family medicine will check certain elements which favor emigration and specialization, and will provide the country with well-trained physicians who can treat most common health problems in the country.
Assuntos
Atenção à Saúde , Medicina de Família e Comunidade , Haiti , Humanos , Cooperação Internacional , PolíticaRESUMO
The potency of ET-1, ET-2, and ET-3 to contract the isolated perfused rat arterial mesenteric bed was 2.73 +/- 0.57, 1.63 +/- 0.32, and 144 +/- 30 nM, respectively. The vasomotor effect of the ETs was slow in onset, persistent but reversible. Sarafotoxin S6b mimicked the ETs with a potency twofold lower than ET-1; sarafotoxin S6c and the C-terminal hexapeptide of ET-1 was inactive. ETH agonists such as IRL-1620 and AGETB-89 were inactive as vasoconstrictors within the range of concentrations examined. Minor chemical modifications of ET-1 amino acids residues in position 7 or 21 decreased significantly the peptide potency; ET-1 analogues with one or none of the disulfide bonds resulted inactive. The vasomotor effect of ETs was blocked in a competitive, reversible, and selective manner by FR 139317 and BQ-123, the latter being about threefold less potent than the former antagonist. The potency of FR 139317 was 20-fold higher to antagonize ET-3 than ET-1, and threefold higher to block ET-2 than ET-1. In strict analogy to FR 139317, BQ-123 was 12-fold more potent to antagonize ET-3 than ET-1, and fourfold more potent to antagonize ET-2 than ET-1. Upon removal of the endothelial cell layer, the vasomotor potency of ET-1 or the antagonist potency of FR 139317 remained unaltered, suggesting that the vasomotor receptors are localized in the arterial smooth muscles. The ET-1-induced vasomotor responses desensitized, an effect not crossed to noradrenaline (NA); perfusion with 10 microM indomethacin did not alter the vasomotor potency of ET-1, excluding the participation of eicosanoids in the arteriolar effects of ET-1. In isolated rings of the rat mesenteric artery, set to record isometric contractions of the circular muscular layer, the potency of the ETs and their structural analogues was as follows; ET-2 = ET-1 = sarafotoxin S6b > ET-3 > sarafotoxin S6c. The C-terminal hexapeptide of ET-1 and [Ala 1,3,11,15]ET-1 were inactive. The ET-1-induced vasoconstriction was antagonized in a concentration-dependent fashion by FR 139317. These results allow to conclude that the ETA receptors present in the arterial mesenteric circulation are localized in the vascular smooth muscle of the large-sized arteries as well as the smaller arterioles and precapillary vessels of the rat arterial mesenteric bed.
Assuntos
Artérias Mesentéricas/metabolismo , Músculo Liso Vascular/metabolismo , Receptores de Endotelina/metabolismo , Animais , Azepinas/farmacologia , Antagonistas dos Receptores de Endotelina , Indóis/farmacologia , Masculino , Peptídeos Cíclicos/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Biopsies of human internal mammary artery and saphenous vein were examined to ascertain the functional integrity of these vessels employed in myocardial revascularization. Studies were performed in vascular rings derived from 28 patients without previous consideration of age, sex, underlying additional pathology or drug treatments previous to and during surgery. Isometric muscle contraction of the circular muscle layer was monitored. Endothelin-1 (ET) is equipotent as a vasoconstrictor in arteries and veins, with a potency at least 10 to 100-fold that of noradrenaline (NA) or serotonin (5-HT). The potency of ET, NA or 5-HT is unaltered by mechanical removal of the endothelial cell layer. Arterial rings precontracted with NA relaxed in a concentration-dependent fashion in the presence of acetylcholine and sodium nitroprusside. Whereas the potency of nitroprusside was unaltered by removal of the endothelium, the efficacy of acetylcholine was greatly reduced. Saphenous vein rings were refractory to acetylcholine but not nitroprusside. Results open new perspectives to explain the larger patency of internal mammary artery grafts as compared to that of saphenous vein grafts in human myocardial revascularization.
Assuntos
Artéria Torácica Interna/efeitos dos fármacos , Revascularização Miocárdica , Veia Safena/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Feminino , Humanos , Masculino , Artéria Torácica Interna/fisiologia , Veia Safena/fisiologia , Vasoconstrição , VasodilataçãoRESUMO
Thirty-six patients with AIDS and culture-proven nontuberculous mycobacteriosis were compared to 20 patients with acquired immunodeficiency syndrome (AIDS) and tuberculosis with regard to clinical signs, symptoms, and diagnostic methods. Patients with nontuberculous mycobacteriosis were more often younger and homosexuals, while patients with tuberculosis were usually Haitian-American or users of intravenous drugs. A majority of patients with tuberculosis presented with fever and weight loss. These symptoms were seen in approximately 50 percent of the patients with nontuberculous mycobacteriosis. A distinct syndrome of dyspnea, chills, hemoptysis, and chest pain was seen in a significant minority of patients with nontuberculous mycobacteriosis. Lymphadenopathy was seen almost exclusively in patients with tuberculosis. Pulmonary sources (expectorated sputum or bronchoscopy specimens) were the most common source of diagnosis in both groups. Patients in both groups in whom the diagnosis was obtained from pulmonary sources frequently had negative chest x-ray films on presentation. Cavitary disease was absent from both groups.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Infecções por Mycobacterium não Tuberculosas/etiologia , Infecções por Mycobacterium/etiologia , Infecções Oportunistas/etiologia , Tuberculose Pulmonar/etiologia , Adulto , Fatores Etários , Broncoscopia , Feminino , Haiti/etnologia , Homossexualidade , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Fatores de Risco , Escarro/microbiologia , Transtornos Relacionados ao Uso de Substâncias , Tuberculose Pulmonar/diagnóstico , Estados UnidosRESUMO
Twenty Haitian patients, hospitalized from 1 April 1980 to 20 June 1982, had Pneumocystis carinii pneumonia, central nervous system toxoplasmosis, esophageal candidiasis, cryptococcosis, disseminated cytomegalovirus, progressive herpes simplex virus, chronic enteric coccidiosis, or invasive Kaposi's sarcoma. Ten patients died. Opportunistic infections were frequently multiple and were recurrent in three patients. In seven patients disseminated tuberculosis preceded the other infections by 2 to 15 months. There was no evidence of an underlying immunosuppressive disease, and no history of homosexuality or intravenous drug abuse. At least three patients probably acquired the syndrome in Haiti. Lymphadenopathy was common. Seventeen patients tested had anergy, and 18 had lymphopenia. Monoclonal antibody analysis of peripheral-blood T-cell subsets done on 11 patients showed a marked decrease in T-helper cells and an inversion of the normal ratio of T-helper cells to T-suppressor cells. This syndrome among heterosexual Haitians is strikingly similar to the syndrome of immunodeficiency described recently among American homosexuals.