Adiponectin regulates albuminuria and podocyte function in mice

Increased albuminuria is associated with obesity and diabetes and is a risk factor for cardiovascular and renal disease. However, the link between early albuminuria and adiposity remains unclear. To determine whether adiponectin, an adipocyte-derived hormone, is a communication signal between adipocytes and the kidney, we performed studies in a cohort of patients at high risk for diabetes and kidney disease as well as in adiponectin-knockout (Ad(-/-)) mice. Albuminuria had a negative correlation with plasma adiponectin in obese patients, and Ad(-/-) mice exhibited increased albuminuria and fusion of podocyte foot processes. In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens-1 translocation to the membrane. These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes. Ad(-/-) mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress. These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes.     

Low coverage but few inclusion errors in Burkina Faso: a community-based targeting approach to exempt the indigent from user fees

Background  

User fees were generalized in Burkina Faso in the 1990 s. At the time of their implementation, it was envisioned that measures would be instituted to exempt the poor from paying these fees. However, in practice, the identification of indigents is ineffective, and so they do not have access to care. Thus, a community-based process for selecting indigents for user fees exemption was tested in a district. In each of the 124 villages in the catchment areas of ten health centres, village committees proposed lists of indigents that were then validated by the health centres' management committees. The objective of this study is to evaluate the effectiveness of this community-based selection.     

Chloroquine and sulphadoxine-pyrimethamine efficacy for uncomplicated malaria treatment and haematological recovery in children in Bobo-Dioulasso,Burkina Faso during a 3-year period 1998-2000

We determined the parasitological resistance and the clinical failure to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) by the WHO 14-day in vivo test over three consecutive years in 948 children aged 6-59 months with uncomplicated malaria attending four health centres in the province of Houet, Burkina Faso. Children were alternatively allocated to either CQ or SP. Packed cell volume (PCV) was measured at days 0 and 14. Parasitological resistance (RI, RII and RIII) to CQ was 18% (83 of 455) and to SP <1% (two of 308). Clinical failure with CQ was 12% (53 of 455) with no evidence of increase over time. Only one case of clinical failure was detected among the children treated with SP. The prevalence of anaemia (PCV <25%) was about 40% at day 0 and had decreased substantially by day 14 in both groups. However, in children treated with SP the prevalence of anaemia at day 14 was significantly lower than in those treated with CQ:RR = 3.15 (95% CI: 1.33-7.42, P = 0.008). CQ and SP are still efficacious for the treatment of uncomplicated malaria in children, at least in this area of Burkina Faso. However, the prevalences of CQ resistance reported from other areas of the country are worrying because of its potential spread. Regular surveillance of resistance to commonly used antimalarial drugs should continue.     

Downregulation of epidermal growth factor receptor signaling by singlet oxygen through activation of caspase-3 and protein phosphatases

Downregulation of survival signaling pathways contributes to the cytotoxicity of reactive oxygen species (ROS) and may underlie certain therapies for hyperproliferative diseases. We have investigated the role of singlet oxygen, an ROS formed by photosensitization, in the regulation of survival signaling via the epidermal growth factor receptor (EGFR). Exposure of human keratinocytes to singlet oxygen resulted in rapid loss of EGFR, which was not blocked by either inhibition of receptor internalization or by interrupting the major proteolytic pathways (proteasome, lysosome or calpain). However, pretreatment with a caspase-3 inhibitor, DEVD-FMK, inhibited EGFR degradation. Caspase-3 cleavage was detected as early as 5 min after singlet oxygen treatment, and recombinant active caspase-3 completely cleaved EGFR in a keratinocyte membrane fraction. The singlet oxygen-induced loss of EGFR was accompanied by dephosphorylation of EGFR as well as of Akt and extracellular signal-regulated kinase 1/2 (ERK)1/2. Singlet oxygen-induced protein dephosphorylation was not dependent on activation of caspase-3. In contrast, inhibition of protein phosphatases (PPs) with okadaic acid completely blocked dephosphorylation of EGFR, ERK1/2 and Akt as well as degradation of EGFR. These results indicate that the oxidative stress produced by singlet oxygen rapidly disrupts EGFR-mediated signaling by decreasing both the protein level and its phosphorylation. These responses depended on intertwined activation of caspase-3 and PPs.     

Determination of plasma alpha-amylase in the dog: a test of the specificity of new methods

Commercially available chromogenic substrates for the assay of alpha-amylase were tested for specificity in dog plasma. Blocked alpha-4-nitrophenylmaltoheptaoside and non-blocked beta-4-nitrophenylmaltoheptaoside showed no interference with glucoamylase and were suitable for the measurement of alpha-amylase in dog plasma. In contrast, an alpha-4-nitrophenylmaltoheptaoside showed interference, and was therefore an inappropriate substrate. Reference values with the blocked substrate in a group of 82 non-selected 3 month- to 10 year-old male and female dogs were 355 +/- 131 U/l (mean +/- standard deviation) at 30 degrees C.     

Child malaria treatment practices among mothers in the district of Yanfolila, Sikasso region, Mali

We studied child malaria treatment practices among mothers living in the District of Yanfolila in southern Mali. For sampling, we first chose five of 13 health areas with probability proportional to size. Then villages, compounds and mothers with at least one child aged 1-5 years were randomly chosen. We assessed the spleen size of one 1-5 year-old child of each mother, collected a thick blood film and recorded the body temperature of every child whose mother thought he/she was sick. 399 mothers in 28 villages were interviewed with a structured questionnaire divided into two parts. If the child had had soumaya (a term previously associated with uncomplicated malaria) during the past rainy season, we asked about signs and symptoms, health-seeking behaviour (who the mother consulted first) and treatment. If not, information about knowledge of the disease and treatment to be given was collected. 86% of the mothers interviewed stated that their child had been sick and almost half of them had had soumaya. All mothers named at least one sign by which they recognized the disease. Vomiting, fever and dark urine/yellow eyes/jaundice were the three most common signs mentioned. 75.8% managed their child's disease at home and used both traditional and modern treatment. The most common anti-malarial drug was chloroquine, often given at inappropriate dosage. The sensitivity and specificity of the mothers' diagnosis was poor, although this might be explained by the large percentage of children who had already been treated at the time of the interview. The results of our survey call for prompt educational action for the correct treatment of uncomplicated malaria/soumaya, particularly for mothers and possibly for shopkeepers. The high spleen rate (58.1%) among randomly selected children confirms that malaria is a common disease in this area. Improved case-management at home could only be beneficial.     

Compared characteristics of peripheral facial paralysis according to HIV status in Bobo-Dioulasso (Burkina Faso)

Facial paralysis is a well-described manifestation of HIV infection. We report 27 cases of peripheral facial paralysis observed at Bobo-Dioulasso Hospital in a prospective study over a period of 9 months: 55 of the cases were HIV positive and 12/15 (80%) were in the 20-39 age group. Nine out of 11 females and 6 out of 16 males were seropositive. 13 of the cases were at stage B of CDC classification and 2 at stage C. ESR was elevated in all the HIV patients. CSF examination revealed lymphocytic pleiocytosis, elevated proteins and a positive HIV serology. CD4 counts were obtained in 8 cases and were under 400/mm3 in 4 cases. The clinical presentation was more severe in HIV seropositives with a longer duration of symptoms. Isolated peripheral facial paralysis associated with an elevated ESR in young adults suggest HIV infection and should lead to HIV counselling and testing.     

Trachoma,flies and environmental factors in Burkina Faso

The presence of flies is one of the earliest risk factors for trachoma and it has been suggested that flies could act as vectors for transmission of chlamydiae. A national trachoma survey was conducted in 1997 in Burkina Faso to (i) study the relationship between trachoma occurrence, flies, dirty faces and some environmental factors, and (ii) investigate the role of flies in the presence of trachoma. The country was stratified into eight groups of provinces and a random sample of 30 clusters was selected in each group. All children aged < 10 years were examined for the diagnosis of active trachoma (trachomatous inflammation which was follicular and/or intense) and the dirtiness of the face and the presence of flies on the face were recorded. The children's carers were questioned about the number of baths given and daily face-washing. Household heads were asked about ownership of cattle and small ruminants. The presence of latrines, a stable, and garbage collection inside the yard was noted. Among 16,514 children examined, 27.0% had active trachoma and 3.3% intense inflammatory trachoma. Flies were present on 11.2% of children's faces and 82.4% and 19.7% of these children had active and intense inflammatory trachoma, respectively. Among the 30.2% of children with dirty faces, 70.2% had active and 10.2% intense inflammatory trachoma. In multivariate analysis, at least one daily bath showed a protective effect on both active and intense inflammatory trachoma. Face-washing twice daily was found to be significantly protective for active trachoma in some regions. A strong association was demonstrated between the presence of flies and dirty faces (odds ratio = 334, 95% confidence interval 202-546). The presence of flies on children's faces, dirty faces and trachoma appeared to be strongly associated. Although the presence of flies may be a marker of socio-economic status and is probably linked with other trachoma risk factors, our data indicated that interventions targeting fly control should be an important issue in controlling trachoma.     

Preliminary information to patients and presentation by Burkinabe physicians of the results of HIV detection test in Burkina Faso

BACKGROUND: The action of individuals and their family is determining in the result of AIDS control and the knowledge of people's serological situation facilitates their involvement in AIDS control. This study was carried out in order METHODS: A transversal investigation through a self-administered anonymous questionnaire was carried out among the 250 Burkinabe physicians working in a public, private or religious health care sector. The questionnaire was sent by mail, attached to a response coupon. A response of 74% was obtained. RESULTS: Seventy seven physicians, that is 48.7% of the sample, informed patients who were likely to be HIV infected about their intention to ask for an HIV test. Seventy five physicians, that is 47.5% of the sample informed patients on the results of their serological tests on HIV infection. The characteristics of physicians who informed customers on the results of their serological test were similar to those of physicians who informed their patients on the demand for test concerning them. There were often specialists, physicians with long experience in medical practice and physicians more involving in curative consultations than in preventive ones (respectively 54.7% versus 23.3%, p=0.002). CONCLUSIONS: These results show the necessity of providing young physicians with counselling training, especially general practitioners who should be working in prevention services. Moreover, they constitute a basis for an objective discussion between physicians working in hospital, officials in charge of the national program for AIDS control and medical training schools.     

Association between bacterial vaginosis and Herpes simplex virus type-2 infection: implications for HIV acquisition studies

OBJECTIVES: Bacterial vaginosis (BV) and Herpes simplex virus type-2 (HSV-2) have been linked to an increased risk of HIV-1 acquisition. Recent research suggests an association between BV and HSV-2 acquisition, but the converse has not been studied. Here, we investigate whether an association exists between BV and HSV-2 infection METHODS: We examined the determinants of BV occurrence in a cohort of female sex workers in Burkina Faso. Participants were followed every 3 months for diagnosis of genital infections and report of sexual behaviours. Factors associated with BV occurrence were assessed using generalised estimating equation models. RESULTS: We enrolled 273 women (mean age, 28 years) and conducted 812 follow-up visits (mean 2.93 visit per woman). Baseline seroprevalence of HIV-1, HSV-2 and recent syphilis were 31.5%, 70.1% and 0.4%, respectively, while baseline prevalence of BV, Trichomonas vaginalis (TV) and Candida albicans were 20.5%, 3.3% and 2.5%, respectively. In multivariable analysis, HSV-2 (relative risk (RR) = 1.73, 95% CI 1.12 to 2.65), HIV-1 (RR = 1.76, 95% CI 1.30 to 2.40), TV (RR = 1.5, 95% CI 1.0 to 2.3), and having > or = 3 sexual partners in the preceding week (RR = 2.2, 95% CI 1.1 to 4.6) were independently associated with BV, while hormonal contraception showed a protective effect (RR = 0.11, 95% CI 0.02 to 0.70). CONCLUSIONS: HSV-2 infection was associated with BV occurrence in this population. As HSV-2 is strongly linked to HIV-1 acquisition, studies assessing the cofactor effect of BV on HIV acquisition should control for the presence of HSV-2. Further studies are required to investigate the relative effect of asymptomatic HSV-2 shedding and/or genital ulcerations on BV occurrence.