In vitro metabolism of moxidectin in Haemonchus contortus adult stages

We studied the implication of cytochrome P450 enzymes in the in vitro metabolism of moxidectin (MXD) in homogenates of Haemonchus contortus adult stages (susceptible isolate, Weybridge, UK). After homogenisation in a phosphate buffer, 2 ml of homogenates (equivalent to 1 g of nematodes) were incubated with 5 microg [14C] MXD at 37 degrees C for 24 h. MXD and its metabolites were separated by HPLC with radiodetection on-line. Only one metabolite was detected and its production was inhibited by carbon monoxide. This result demonstrates that the cytochrome P450 system is implicated in the metabolisation of MXD in H. contortus susceptible to milbemycin. Furthermore, this metabolite did not match those previously described in vertebrates.     

The relationship of carditis to the initial attack of Sydenham's chorea

BACKGROUND: The natural history of valvular regurgitation detected by echocardiography in Sydenham's chorea has been lacking. METHODS: Clinical assessment and transthoracic color Doppler echocardiography were independently performed for each patient with an initial attack of Sydenham's chorea and also for each normal control (Khon Kaen University, Thailand; 1991-2001) at the time of their presentations. Serial clinical examinations and echocardiography were done for each patient at 1- and at 5-year follow-up. RESULTS: Of 44 patients, 17 (39%) had carditis (valvulitis) evident by auscultation at the time of the initial attack. Three (11%) of the 27 patients with no clinical evidence of carditis had echocardiographic evidence of acute mitral regurgitation (subclinical valvulitis). All 17 patients with carditis had echocardiographic evidence of acute mitral regurgitation. None of the 88 control children had evidence of pathologically significant valvular regurgitation. Of the 15 patients with carditis regularly followed, the persistence of a mitral regurgitation murmur and of pathologically significant valvular regurgitation by echocardiography were 33% (5/15) and 60% (9/15), respectively, at 1-year follow-up, but the persistence of both was 25% (1/4) at 5-year follow-up. CONCLUSIONS: Color Doppler echocardiography is a useful tool in the early diagnosis of rheumatic carditis (valvulitis) and at 1-year follow-up of rheumatic valvular heart disease in the patients with initial Sydenham's chorea but the incremental benefit beyond 5 years after the initial attack might be minimal.     

Rate of dopamine metabolism in the rabbit carotid body in vivo

In the rabbit carotid body (CB) in vivo, the rate of dopamine metabolism was estimated to 44.4±3.9 (SD) pmol/CB/h from the decrease in dihydroxyphenylacetic acid content after pargyline inhibition of monoamine oxidase.     

The influence of parasitism on the pharmacokinetics of moxidectin in lambs

Most pharmacokinetic studies on anthelmintic drugs have been performed on non-parasitized animals. However, it seems likely that the parasite burden could influence the deposition of such drugs. The pharmacokinetics of moxidectin administered orally and by subcutaneous injection was compared in lambs exposed to nematode infection and in parasite naive lambs. Plasma samples were analyzed for moxidectin over 40 days post-treatment. The main pharmacokinetic parameters calculated demonstrated a significant change in drug deposition in infected lambs when compared to controls. The area under the plasma concentration—time curve was decreased 54% and 46% by infection in the subcutaneous and oral groups, respectively. There was also a major decrease in the mean residence time in parasitized lambs. In parallel, the clearance of the drug was increased by infection. Thus, parasite infection dramatically influences the disposition of moxidectin in lambs. These results may contribute to determining a therapeutic strategy adapted to heavily infested animals.     

Fate of the catecholamine stores in the rabbit carotid body superfused in vitro

In rabbit carotid bodies (CBs) superfused during 1–5 h, with an air-equilibrated medium containing no tyrosine (TYR), the dopamine (DA) content decreased by approximately 60% after 1 h and remained constant afterwards. TYR and 3,4-dihydroxyphenylacetic acid (DOPAC) decreased with the same time course. Noradrenaline (NA) content exhibited a biphasic decrease of lesser magnitude than that of DA. Superfusions with a TYR-containing medium did not prevent the reduction in DA and TYR. Large amounts of DA and DOPAC were recovered in the effluent during the first hour of superfusion but after 90 min the two substances had declined below the detection limits (i.e. 0.5 and 1 pmol/5 min, respectively). The DA efflux decreased exponentially during the first hour and was not altered by changing the oxygen partial pressure (PO₂) of the medium. The DOPAC efflux declined after 40 min of superfusion and was modulated byPO₂. The DA and the DOPAC effluxes were not suppressed by omitting calcium ions from the superfusing medium. In 4 cat CBs equal amounts of DA and NA were recovered from the effluent during the first hour of superfusion.     

Biomarkers of Redox Balance Adjusted to Exercise Intensity as a Useful Tool to Identify Patients at Risk of Muscle Disease through Exercise Test

The screening of skeletal muscle diseases constitutes an unresolved challenge. Currently, exercise tests or plasmatic tests alone have shown limited performance in the screening of subjects with an increased risk of muscle oxidative metabolism impairment. Intensity-adjusted energy substrate levels of lactate (La), pyruvate (Pyr), β-hydroxybutyrate (BOH) and acetoacetate (AA) during a cardiopulmonary exercise test (CPET) could constitute alternative valid biomarkers to select “at-risk” patients, requiring the gold-standard diagnosis procedure through muscle biopsy. Thus, we aimed to test: (1) the validity of the V’O₂-adjusted La, Pyr, BOH and AA during a CPET for the assessment of the muscle oxidative metabolism (exercise and mitochondrial respiration parameters); and (2) the discriminative value of the V’O₂-adjusted energy and redox markers, as well as five other V’O₂-adjusted TCA cycle-related metabolites, between healthy subjects, subjects with muscle complaints and muscle disease patients. Two hundred and thirty subjects with muscle complaints without diagnosis, nine patients with a diagnosed muscle disease and ten healthy subjects performed a CPET with blood assessments at rest, at the estimated 1st ventilatory threshold and at the maximal intensity. Twelve subjects with muscle complaints presenting a severe alteration of their profile underwent a muscle biopsy. The V’O₂-adjusted plasma levels of La, Pyr, BOH and AA, and their respective ratios showed significant correlations with functional and muscle fiber mitochondrial respiration parameters. Differences in exercise V’O₂-adjusted La/Pyr, BOH, AA and BOH/AA were observed between healthy subjects, subjects with muscle complaints without diagnosis and muscle disease patients. The energy substrate and redox blood profile of complaining subjects with severe exercise intolerance matched the blood profile of muscle disease patients. Adding five tricarboxylic acid cycle intermediates did not improve the discriminative value of the intensity-adjusted energy and redox markers. The V’O₂-adjusted La, Pyr, BOH, AA and their respective ratios constitute valid muscle biomarkers that reveal similar blunted adaptations in muscle disease patients and in subjects with muscle complaints and severe exercise intolerance. A targeted metabolomic approach to improve the screening of “at-risk” patients is discussed.     

Occurrence of ectoparasites on rodents in Sukhothai Province, northern Thailand

A survey of ectoparasites on rodents was carried out bimonthly from April 2008 to March 2009 in 3 districts of Sukhothai Province, northern Thailand. A total of 130 rodents comprising 8 species of hosts were captured and examined for ectoparasites. The hosts examined were Bandicota indica, Bandicota savilei, Rattus losea, Rattus rattus, Rattus exulans, Rattus norvegicus, Menetes berdmorei and Tamiops mcclellandii. Ninety-seven ectoparasites were collected: 1 species of tick (Hemaphysalis bandicota), 2 species of mites (Laelaps nuttali and Laelaps echidninus), and 1 species of flea (Xenopsylla cheopis) were identified. The infestation rates by ticks, mites and fleas on the rodents were 0.77, 5.38 and 6.15%, respectively. Monitoring the rodent population and their ectoparasites is important for future planning of prevention and control of zoonotic diseases in the area.     

The pattern of diarrhea in children in Khon Kaen, northeastern Thailand: I. The incidence and seasonal variation of diarrhea

The incidence, seasonal variation and risk factors of diarrhea in children in Thailand are not well defined. The objective of this study is to identify the incidence and seasonal variation of diarrhea in a rural community. A cohort of 481 children under five years of age from 14 villages in rural northeastern Thailand was followed for 1 year, from May 1988 to April 1989. The data were collected daily by 5 participant observers who resided in the villages during the study period. During the 25,012 person weeks of surveillance, 384 episodes of diarrhea occurred; 279 episodes (72.7%) were watery diarrhea and 105 episodes (27.3%) were dysentery-like diarrhea. The incidence of diarrhea was 2.1, 1.76, 0.96 and 0.45 episodes per child per year for children aged 0-6 months, 7-12 months, 1 year and above 2 years, respectively. Males were affected as frequently as females. The average duration of illness was 4.9, 2.1, 1.5 and 0.5 days per child per year for children aged under 1 year, 1-2 years, 2-3 years and more than 3 years old, respectively. Both dysentery and watery diarrhea rates peaked for children of all ages from May to July, during the early rainy season. A second peak of watery diarrhea in the winter from November to January and was seen primarily in children less than 2 years old. The monthly incidence of diarrhea was associated with rainfall, ambient temperature and occupational behavior of people in each season.