Potential role of sylvatic and domestic African mosquito species in dengue emergence

Dengue virus 2 (DENV-2) strains that circulate in sylvatic habitats of Senegal and other parts of west Africa are believed to represent ancestral forms that evolved into endemic/epidemic strains that now circulate widely in urban areas of the tropics. Previous studies suggested that the evolution of the endemic/epidemic strains was mediated by adaptation to the peridomestic mosquito vectors Aedes aegypti and Ae. albopictus. We conducted experimental infections using sylvatic and peridomestic Senegalese mosquitoes, and both sylvatic and urban DENV-2 strains to determine if endemic DENV-2 adaptation was vector species specific, and to assess ancestral vector susceptibility. Aedes furcifer and Ae. luteocephalus, probable sylvatic vectors, were highly susceptible to both sylvatic and urban DENV-2 strains. In contrast, sylvatic Ae. vittatus and both sylvatic and peridomestic populations of Ae. aegypti were relative refractory to all DENV-2 strains tested. These results indicate that adaptation of DENV-2 to urban vectors did not result in a loss of infectivity for some African sylvatic vectors. Implications for dengue emergence in west Africa are discussed.     

IgE antibodies to Plasmodium falciparum and severity of malaria in children of one ethnic group living in Burkina Faso

Plasmodium falciparum malaria infection induces elevated blood levels of both total immunoglobulin and anti-plasmodial antibodies belonging to different isotypes. We have previously shown that donors living in areas of malaria transmission develop malaria-specific IgE antibodies that are present at highest concentrations in patients with severe disease, suggesting a role for this isotype in malaria pathogenesis. To establish the possible importance of IgE in the course and severity of this disease, we have analyzed a large and homogenous group of African children (age range = 6 months to 15 years) belonging to one ethnic group (Mossi) living in identical epidemiologic conditions in the same urban area (Ougadougo) of Burkina Faso. While IgG antibodies to P. falciparum increased to high concentrations in very young children and then remained at these levels in older patients, IgE antibodies increased with age, becoming most significantly elevated in children more than four years of age. In older children, those with severe malaria had significantly higher IgE antibody levels than those with non-severe disease. No significant differences between the patient groups were seen for IgG antibodies to P. falciparum. However, when the patients with severe malaria were divided into two groups distinguished by the presence of absence of coma, both IgG and IgE antibodies against malaria were lower in the comatous patients than in the non-comatous patients. The results support the conclusion that IgE antibodies against malaria, regardless of their possible protectivity, also contribute to disease severity in this large and homogenous group of African children.     

Lower levels of the circulating neuropeptide somatostatin in Schistosoma mansoni infected patients may have pathological significance

In recent years, cases of severe morbidity (fibrosis, haematemesis, hepatosplenomegaly, ascites) caused to Schistosoma mansoni infections are on the rise in Northern Senegal. The neuropeptide somatostatin is reported to decrease portal pressure, control variceal bleeding and fibrosis, and reduce Schistosoma-caused clinical morbidity in the rodent model. The aim of this study was to delineate the role of somatostatin in S. mansoni-caused pathogenesis, by studying host levels of somatostatin in the peripheral blood of uninfected and S. mansoni-infected individuals. Subjects from the district dispensary at Richard Toll, in the Medical Region of Saint-Louis, Senegal, infected with S. mansoni and suffering from severe morbidity were selected. A separate group consisted of individuals resident in the same region but uninfected at the time of the study. Significantly lower somatostatin levels were detected in severe morbidity patients, compared with the exposed but uninfected subjects. In patients with schistosomiasis physiological levels of somatostatin may determine disposition of particular individuals towards severe morbidity, as opposed to others. Host pathology can thus be alleviated by the therapeutic ability of somatostatin to treat bleeding oesophageal varices, reduce portal pressure and prevent progression to severe fibrosis.     

Na+/H+ exchange inhibition with cardioplegia reduces cytosolic [Ca2+] and myocardial damage after cold ischemia

Cold cardioplegia protects against reperfusion damage. Blocking Na+/H+ exchange may be as protective as cardioplegia by improving the left ventricular pressure (LVP)-[Ca2+] relationship after cold ischemia. In guinea pig isolated hearts subjected to cold ischemia (4 h, 17 degrees C) and reperfusion, the cardioprotective effects of a Krebs-Ringer (KR) solution, a cardioplegia solution, a KR solution containing the Na+/H+ exchange inhibitor eniporide (1 microM), and a cardioplegia solution containing eniporide were compared. Treatments were given before and initially after cold ischemia. Systolic and diastolic [Ca2+] were calculated from indo-1 fluorescence transients recorded at the LV free wall. During ischemia, diastolic [Ca2+] increased in each group but more so in the KR group. Peak systolic and diastolic [Ca2+] on initial reperfusion were highest after KR and smallest after cardioplegia + eniporide. After reperfusion, systolic-diastolic LVP (% of baseline) and infarct size (%), respectively, were KR, 47 +/- 3%, 37 +/- 4%; cardioplegia, 71 +/- 5%*, 20 +/- 2.2%*; KR + eniporide, 73 +/- 5%*, 11 +/- 3%* dagger; and cardioplegia + eniporide 77 +/- 3%*, 10 +/- 1.4%* dagger (*P 相似文献   

Sevoflurane preconditioning before moderate hypothermic ischemia protects against cytosolic [Ca(2+)] loading and myocardial damage in part via mitochondrial K(ATP) channels

BACKGROUND: Brief sevoflurane exposure and washout (sevoflurane preconditioning [SPC]) before 30-min global ischemia at 37 degrees C is known to improve cardiac function, decrease cytosolic [Ca(2+)] loading, and reduce infarct size on reperfusion. It is not known if anesthetic preconditioning (APC) applies as well to hypothermic ischemia and reperfusion and if K(ATP) channels are involved. The authors examined in guinea pig isolated hearts the effect of sevoflurane exposure before 4-h global ischemia at 17 degrees C on cardiac function, cytosolic [Ca(2+)] loading, and infarct size. In addition they tested the potential role of the mitochondrial K(ATP) channel in eliciting the cardioprotection by SPC. METHODS: Hearts were randomly assigned to (1) a nontreated hypothermic ischemia group (CON), (2) a group given 3.5 vol% sevoflurane for 15 min with a 15-min washout before hypothermic ischemia (SPC), and (3) an SPC group in which anesthetic exposure was bracketed with 200 microm 5-hydroxydecanoate (5-HD) from 5 min before until 5 min after sevoflurane (SPC + 5-HD). Cytosolic [Ca(2+)] was measured in the left ventricular (LV) free wall with the intracellularly loaded fluorescence probe indo-1. RESULTS: Initial reperfusion in CON hearts markedly increased systolic and diastolic [Ca(2+)] and reduced contractility (dLVP/dt(max)), relaxation (diastolic LVP, dLVP/dt(min)), myocardial oxygen consumption (MvO(2)), and cardiac efficiency. In SPC hearts, cytosolic [Ca(2+)] overloading (especially diastolic [Ca(2+)]) was decreased with increased myocardial [Ca(2+)] influx (d[Ca(2+)]/dt(max)) and efflux (d[Ca(2+)]/dt(min)), improved contractility, relaxation, coronary flow, MvO(2), cardiac efficiency, and decreased infarct size. In SPC + 5HD hearts, the reduction in infarct size was antagonized by 5-HD, but functional return was less affected by 5-HD. CONCLUSIONS: Anesthetic preconditioning occurs after long-term hypothermic ischemia, and the infarct size reduction is the result, in part, of mitochondrial K(ATP) channel opening.     

Anatomic bases of graciloplasty using end-to-side nerve pudendal anastomosis

The objective of this study was to evaluate the possibilities of reinnervation of the gracilis muscle, transposed around the anus, by the pudendal nerve using an end-to-side nerve anastomosis. This study was carried out in 14 cases (7 adult human cadavers bilaterally). The gracilis muscle and its vascular-nervous bundle have been dissected and the nerve innervating the gracilis muscle has been cut at its origin. The gracilis muscle, accompanied by its nerve, has then been transposed around the anus. The pudendal nerve has been dissected from its extrapelvic part. The reinnervation using an end-to-side nerve anastomosis has been considered as feasible when the proximal ending of the nerve of the gracilis was put into a tension-free contact with the extrapelvic part of the pudendal nerve. The extrapelvic part of the pudendal nerve has a common trunk in 12 cases. The width of the extrapelvic part of the pudendal nerve was 2.6±0.7 mm, range 1–3.5. The width of the proximal endings of the nerve innervating the gracilis muscle was 2.3±0.5 mm, range 2–3. The reinnervation of the gracilis muscle by the pudendal nerve has been possible in 14 cases. An average supplementary length of 17.4±15.4 mm was available (range 5–52). These results suggest an eventual practical aspect of this technique for the reconstruction of a functional sphincter using the gracilis muscle transposed around the anus.     

Chronic long-term exposure to cadmium air pollution and breast cancer risk in the French E3N cohort

Cadmium, due to its estrogen-like activity, has been suspected to increase the risk of breast cancer; however, epidemiological studies have reported inconsistent findings. We conducted a case–control study (4,059 cases and 4,059 matched controls) nested within the E3N French cohort study to estimate the risk of breast cancer associated with long-term exposure to airborne cadmium pollution, and its effect according to molecular subtype of breast cancer (estrogen receptor negative/positive [ER−/ER+] and progesterone receptor negative/positive [PR−/PR+]). Atmospheric exposure to cadmium was assessed using a Geographic Information System-based metric, which included subject's residence-to-cadmium source distance, wind direction, exposure duration and stack height. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Overall, there was no significant association between cumulative dose of airborne cadmium exposure and the risk of overall, premenopausal and postmenopausal breast cancer. However, by ER and PR status, inverse associations were observed for ER− (OR_{Q5 vs. Q1} = 0.63; 95% CI: 0.41–0.95, p_trend = 0.043) and for ER−/PR− breast tumors (OR_{Q4 vs. Q1} = 0.62; 95% CI: 0.40–0.95, OR_{Q5 vs. Q1} = 0.68; 95% CI: 0.42–1.07, p_trend = 0.088). Our study provides no evidence of an association between exposure to cadmium and risk of breast cancer overall but suggests that cadmium might be related to a decreased risk of ER− and ER−/PR− breast tumors. These observations and other possible effects linked to hormone receptor status warrant further investigations.     

Impact of mosquito bites on asexual parasite density and gametocyte prevalence in asymptomatic chronic Plasmodium falciparum infections and correlation with IgE and IgG titers

An immunomodulatory role of arthropod saliva has been well documented, but evidence for an effect on Plasmodium sp. infectiousness remains controversial. Mosquito saliva may orient the immune response toward a Th2 profile, thereby priming a Th2 response against subsequent antigens, including Plasmodium. Orientation toward a Th1 versus a Th2 profile promotes IgG and IgE proliferation, respectively, where the former is crucial for the development of an efficient antiparasite immune response. Here we assessed the direct effect of mosquito bites on the density of Plasmodium falciparum asexual parasites and the prevalence of gametocytes in chronic, asymptomatic infections in a longitudinal cohort study of seasonal transmission. We additionally correlated these parasitological measures with IgE and IgG antiparasite and anti-salivary gland extract titers. The mosquito biting density was positively correlated with the asexual parasite density but not asexual parasite prevalence and was negatively correlated with gametocyte prevalence. Individual anti-salivary gland IgE titers were also negatively correlated with gametocyte carriage and were strongly positively correlated with antiparasite IgE titers, consistent with the hypothesis that mosquito bites predispose individuals to develop an IgE antiparasite response. We provide evidence that mosquito bites have an impact on asymptomatic infections and differentially so for the production of asexual and sexual parasites. An increased research focus on the immunological impact of mosquito bites during asymptomatic infections is warranted, to establish whether strategies targeting the immune response to saliva can reduce the duration of infection and the onward transmission of the parasite.