Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification.

AIMS/HYPOTHESIS: Changes in cardiac substrate utilisation leading to altered energy metabolism may underlie the development of diabetic cardiomyopathy. We studied cardiomyocyte substrate uptake and utilisation and the role of the fatty acid translocase CD36 in relation to in vivo cardiac function in rats fed a high-fat diet (HFD). METHODS: Rats were exposed to an HFD or a low-fat diet (LFD). In vivo cardiac function was monitored by echocardiography. Substrate uptake and utilisation were determined in isolated cardiomyocytes. RESULTS: Feeding an HFD for 8 weeks induced left ventricular dilation in the systolic phase and decreased fractional shortening and the ejection fraction. Insulin-stimulated glucose uptake and proline-rich Akt substrate 40 phosphorylation were 41% (p < 0.001) and 45% (p < 0.05) lower, respectively, in cardiomyocytes from rats on the HFD. However, long-chain fatty acid (LCFA) uptake was 1.4-fold increased (p < 0.001) and LCFA esterification into triacylglycerols and phospholipids was increased 1.4- and 1.5-fold, respectively (both p < 0.05), in cardiomyocytes from HFD compared with LFD hearts. In the presence of the CD36 inhibitor sulfo-N-succinimidyloleate, LCFA uptake and esterification were similar in LFD and HFD cardiomyocytes. In HFD hearts CD36 was relocated to the sarcolemma, and basal phosphorylation of a mediator of CD36-trafficking, i.e. protein kinase B (PKB/Akt), was increased. CONCLUSIONS/INTERPRETATION: Feeding rats an HFD induced cardiac contractile dysfunction, which was accompanied by the relocation of CD36 to the sarcolemma, and elevated basal levels of phosphorylated PKB/Akt. The permanent presence of CD36 at the sarcolemma resulted in enhanced rates of LCFA uptake and myocardial triacylglycerol accumulation, and may contribute to the development of insulin resistance and diabetic cardiomyopathy.

Cystic echinococcosis in the Berber of the Mid Atlas mountains, Morocco: new insights into the natural history of the disease in humans.

Precise knowledge of the natural history of cystic echinococcosis (CE) in humans remains somewhat arcane. The aim of the present study was to determine whether aspects of the natural history of established human infection with Echinococcus granulosus could be investigated by using a cross-sectional approach, in a community where CE was endemic. A mass ultrasound-screening survey, coupled with a questionnaire to record all previous surgical histories related to CE, was carried out amongst the primarily transhumant Berber people of the Mid Atlas mountains in Morocco. During two periods of intensive screening, of 10 days in May 2000 and 11 days in May 2001, 11,612 people, representing > 98% of the local population, were checked. One hundred and twenty six (1.1%) of the subjects--75 (59.5%) of the 6864 females investigated and 51 (40.5%) of the 4748 males--were found ultrasound-positive for CE. Overall, 14.1% of the CE cases detected were children aged 1-15 years (who made up 44% of the study population). Most (77.4%) of the ultrasound-positive subjects investigated were also found seropositive for CE. The frequency of a past history of surgery for CE increased with subject age (P = 0.024), 125 (1.1%) of the subjects being recorded as having had such surgery. The frequency of surgery for pulmonary CE was relatively constant in all age-groups, indicating that infection can occur at any time. The frequency of abdominal CE increased with age (R2 = 0.8102). Assuming that the incidence of infection remains fairly constant over time and that the longer a person spends in this endemic area the more likely it is that he or she will develop CE, then a progression from active through transitional to inactive CE should occur. The cysts observed by ultrasound in the present study were categorized, as type 1, 2, 3, 4 or 5, according to the new, standardized, ultrasound classification of CE developed by the World Health Organization (WHO). There was a clear exponential decline in the frequency of the various cyst types, from type 1 (the most frequent) to type 5 (the rarest). This decline validates the assumptions made, about the natural history of established CE, by those who developed the WHO's classification. The classification should therefore be invaluable to surgeons and clinicians, when they have to consider treatment options for patients with the various types of CE, and to policy makers trying to establish the economic costs of treating CE in endemic settings.

Public health education/importance and experience from the field. Educational impact of community-based ultrasound screening surveys.

The public health educational impact of community-based ultrasound (US) surveys for cystic echinococcosis (CE) can form an important part of the development about the awareness of the importance of the disease in an endemic area. In addition to identifying asymptomatic carriers and thereby facilitating early diagnosis and treatment, such surveys can be used to impart important educational messages at the individual, household, community, regional and national levels. US surveys are usually appealing to rural communities where such services are not available but where the technique is generally appreciated by its application in a wide field of medical applications. The qualities of the test (painless, non-invasive and gives instant recordable results) are also attractive to participants during such surveys and the majority of the population in a selected study area choose to be screened. Two such surveys were carried out amongst the Berber people of the mid-Atlas mountains in central Morocco in May 2000 and 2001. Over 11,000 people were screened in the two 10-day surveys. Informed consent had been obtained through community meetings and with the chiefs of villages prior to the surveys being conducted. Individuals who volunteered to be screened entered the study and as far as is known there were no refusals. The concept of voluntary participation, the explanation of the life cycle and clinical manifestations of the disease and its prevention are all-important educational messages. The occurrence of CE is almost always known in an endemic community but is usually very poorly understood leading in many cases to a fear of the disease, especially amongst families with an infected individual who has previously undergone surgery. During the US survey considerable attention was paid to provide educational input before, during and after the survey. Information was provided at the start of the survey to local leaders, doctors, veterinarians and school teachers on the aims of the study and to obtain informed consent. At the start of the study everyone was individually schooled about the route of transmission of the parasite and how this may be best prevented. The knowledge level of those screened was assessed by showing hydatid cysts, either freshly obtained from the abattoir of from photographs. Animal cysts were recognised by almost everyone but its transmission and link to human disease was invariably unknown. Patients found to be infected with CE were always confidentially counselled and followed up for treatment, if required. Treatment options were explained to the individual or to parents in the case of a child. Local physicians participated in discussions on the WHO guidelines for the treatment of CE and all cases were fully discussed providing an educational element for the local doctors. The 1% US prevalence found sent an important message to the local politicians and the perceived importance of the disease had an impact at the leadership level. Local leaders made calls for a control programme. The long term educational impact remains to be evaluated as does the role such surveys play in the future collaboration of communities with the implementation of a control programme.

Prevalence of Theileria in the tick Hyalomma detritum detritum in the Doukkala region, Morocco.

The overall prevalence of Theileria species, mainly, if not exclusively, T.annulata, in 901 Hyalomma detritum detritum collected from cattle in the Doukkala region of Morocco over a period of 2 years was 21.5%. The quantity of infection (number of sporoblasts per infected tick) followed the negative binomial distribution with between one and 250 sporoblasts per infected tick. Infected ticks were found in eight of fourteen areas examined whilst T.annulata was present in all fourteen. There were significant differences in both the prevalence and the quantity of infection between ticks collected from different farms, and between nymphs collected in the autumn from these farms, and moulted in the laboratory, and adults collected in the following summer. The prevalence, but not the quantity, of infection was higher in female than in male ticks. No correlations were established between infection of engorged nymphs and the breed, sex and Theileria piroplasm parasitaemia of the host animal. However, calves infected a greater proportion of nymphs than adult cattle and the heavier the infestation of nymphs on an animal, up to a plateau, the higher the prevalence of infection in those nymphs. There were no differences in infection between ticks moulted at 24 degrees C and 37 degrees C, after the engorged nymphs had been stored at 18 degrees C to simulate over-wintering.