Pharmacokinetics of diminazene in sheep

The pharmacokinetic behavior of diminazene in plasma after administration of 2 mg/kg i.v. and 3.5 mg/kg i.m. was studied in four healthy Dala x Ryggja rams. Following i.v. injection, the data were satisfactorily described by a tri-exponential equation; the apparent volume of distribution at the steady-state was 0.56 +/- 0.04 L/Kg (mean +/- SD; n = 4); total body clearance averaged 1.1 +/- 0.09 ml/kg/min and elimination half-life was 9.30 +/- 1.40 hr. After intramuscular administration peak plasma levels of 6.30-7.57 micrograms/ml were reached in 20 to 45 min and the mean absorption time averaged 5.83 +/- 1.61 hr. Systemic availability relative to the intravenous dose was 95.10 +/- 23.21% and mean residence time averaged 14.16 +/- 1.55 hr. The partition of diminazene between erythrocytes and plasma averaged 0.64 +/- 0.10; plasma protein binding was high (65-85%) and concentration-dependent. Based on the experimental data obtained, an initial i.m. dose of 2.5 mg/kg followed by 2 mg/kg 24 hr later should be safe and effective in cases of babesiosis and trypanosomiasis sensitive to diminazene. A preslaughter withdrawal period of 14-26 days was estimated.     

Cerebral edema and cerebral hemorrhages in interleukin-10-deficient mice infected with Plasmodium chabaudi

During a Plasmodium chabaudi infection in interleukin-10 (IL-10) knockout mice, there is greater parasite sequestration, more severe cerebral edema, and a high frequency of cerebral hemorrhage compared with infection of C57BL/6 mice. Anti-tumor necrosis factor alpha treatment ameliorated both cerebral edema and hemorrhages, suggesting that proinflammatory responses contributed to cerebral complications in infected IL-10(-/-) mice.     

Is transmyocardial revascularisation of benefit in addition to coronary artery bypass grafting for patients with diffuse coronary disease?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the use of transmyocardial revascularisation (TMR) in addition to coronary artery bypass grafting (CABG) is of benefit in patients with ischaemic heart disease with areas of ungraftable myocardium. Altogether 233 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that while the society of thoracic surgeons now recommend TMR+CABG, and the available studies indicate that mortality is not increased by this additional procedure, it is currently not clear whether TMR reduces symptoms of angina in addition to CABG alone.     

BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG?

Previous studies have suggested that the bacille Calmette-Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25-0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24-0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23-0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27-0.79) or 0.42 (0.21-0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria-tetanus-pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.     

Acute toxicity of crude extracts of Aspergillus quadrilineatus isolated from acha (Digitaria exilis Stapf)

In a survey of fungi and mycotoxin conterminating acha (Digitaria exilis Stapf) in Plateau State of Nigeria, 96 fungal isolates were made. Screening of the fungi isolates for their mycotoxin-producing potentials showed that Aspergillus quadrilineatus (Thom and Raper) produced some of the most toxic mycotoxins. Two extracts of the Aspergillus quadrilineatus (the petroleum ether soluble extracts [PER] and the petroleum ether defatted crude extract [PEDCR]) were tested for acute toxicity in mice, chicks and cattle. The ip LD50 of PER in mice was 1148 mg/kg, and the oral LD50 of PEDCR was 566 mg/kg in mice and 556 mg/kg in chicks. The ip LD50 of PEDCR in mice was 21 mg/kg. The toxic signs of PER and PEDCR in mice and chicks included tachypnea, tachycardia, anorexia, somnolence, diarrhea, coma and death. The main postmortem findings were congestion of heart, liver, kidney and lungs and sloughing of the wall of stomach and hemorrhagic enteritis. The histopathologic findings in dead animals included edema and mild degeneration of the myocardium and necrosis of kidney tubular epithelial cells, hepatocytes and bronchioles. The only clinical observation in 1 calf orally dosed with a culture of Aspergillus quadrilineatus of maize was transient whole body tremors which occurred 1 h after dosing, tachycardia and profuse salivation. No significant histopathologic changes were found in the organs of the sacrificed calf.     

Long‐TE 1H MRS suggests that liver fat is more saturated than subcutaneous and visceral fat

Cross‐talk between adipose tissue and liver is disturbed in the metabolic syndrome. Moreover, the relative fatty acid composition of adipose and liver fat is poorly characterized. Long‐TE ¹H MRS can determine the unsaturation and polyunsaturation of adipose tissue. The aim of this study was to use long‐TE ¹H MRS to determine the composition of liver fat and its relation to adipose tissue composition. Sixteen subjects with increased liver fat (>5%) were recruited for the study. Using TE = 200 ms, we were able to resolve the olefinic (?CH, 5.3 ppm) and water (H₂O, 4.7 ppm) resonances in liver spectra and to obtain a repeatable estimate of liver fat unsaturation (coefficient of variation, 2.3%). With TE = 135 ms, the diallylic (?C? CH₂? C?, 2.8 ppm) resonance was detectable in subjects with a liver fat content above 15%. Long‐TE ¹H MRS was also used to determine the unsaturation in subcutaneous (n = 16) and visceral (n = 11) adipose tissue in the same subjects. Liver fat was more saturated (double bonds per fatty acid chain, 0.812 ± 0.022) than subcutaneous (double bonds per fatty acid chain, 0.862 ± 0.022, p < 0.0004) or visceral (double bonds per fatty acid chain, 0.865 ± 0.033, p < 0.0004) fat. Liver fat unsaturation correlated with subcutaneous unsaturation (R = 0.837, p < 0.0001) and visceral unsaturation (R = 0.879, p < 0.0004). The present study introduces a new noninvasive method for the assessment of the composition of liver fat. The results suggest that liver fat is more saturated than subcutaneous or visceral adipose tissue, which may be attributed to differences in de novo lipogenesis. Copyright © 2010 John Wiley & Sons, Ltd.     

Increased apolipoprotein E level and reduced high-density lipoprotein mean particle size associate with low high-density lipoprotein cholesterol and features of metabolic syndrome

The metabolic syndrome (MetS) pandemic predisposes patients to low high-density lipoprotein cholesterol (HDL-C). To successfully treat low HDL-C, there is an urgent need for a better understanding of the changes in HDL particles in the low-HDL-C state. Especially, apolipoprotein (apo) E metabolism in HDL particles is an emerging and important issue. Therefore, we determined HDL subspecies, apo E distribution, and the impact of the MetS in subjects with low and high HDL-C. We studied 246 subjects derived from the Finnish Health 2000 Health Examination Survey. The 2 groups included 113 low-HDL-C (≤10th percentile) and 133 high-HDL-C (≥90th percentile) subjects. The low-HDL-C subjects had higher apo E concentration (39.4 ± 19.4 vs 25.6 ± 8.0 μg/mL, P < .001) and smaller HDL mean particle size (9.0 ± 0.2 vs 9.8 ± 0.3 nm, P < .001). The distribution of apo E genetic isoforms could not explain the difference. Apolipoprotein E content of very low-density lipoprotein particles was comparable between the study groups. In the low-HDL-C subjects, apo E level in large HDL particles was lower (P < .001) compared with that in the high-HDL-C subjects. The subjects with MetS had smaller HDL mean particle size and higher serum apo E concentration. Serum apo E concentration associated positively with different MetS markers (waist circumference, triglycerides, and glucose), whereas HDL mean particle size associated with those negatively. Our results highlight that, in the low-HDL-C state, there are changes in the size and composition of HDL particles associating with MetS. Apolipoprotein E, although generally considered antiatherogenic, associates with MetS and low HDL-C. Our results emphasize the need for a better understanding of apo E metabolism in HDL particles.     

An inulin-type fructan enhances calcium absorption primarily via an effect on colonic absorption in humans

Calcium absorption efficiency and bone mineral mass are increased in adolescents who regularly consume inulin-type fructans (ITF). The mechanism of action in increasing absorption is unknown but may be related to increased colonic calcium absorption. We conducted a study in young adults designed to evaluate these mechanisms with a kinetic technique using (42)Ca orally and (46)Ca dosed i.v. Those who responded to 8 wk of supplementation with 8 g of a mixed short and long degree of polymerization ITF by increasing their calcium absorption had kinetic measurements analyzed to evaluate the time course of absorption. The area under the curve of the oral tracer in the blood during the 26 h after dosing was calculated and the time dependence of increased absorption determined. Eight young adults (of 13 studied), with mean calcium intake approximately 900 mg/d, responded to the ITF with an increased calcium absorption of at least 3%. In responders, absorption increased from 22.7 +/- 11.3% to 31.0 +/- 15.3%. Colonic absorption, defined as absorption that occurred >7 h after oral dosing, represented 69.6 +/- 18.6% of the increase, or 49 +/- 28 mg/d. These findings suggest that, in those who respond to ITF, its effects on calcium absorption occur principally in the colon. This benefit to ITF may be especially important when absorption in the small intestine is impaired for anatomic or physiological reasons.     

Incidence of infections dues to Escherichia coli strains producing extended spectrum betalactamase, in the Zou/Collines Hospital Centre (CHDZ/C) in Benin

OBJECTIVES: Over a 6-month period, extended-spectrum betalactamase (ESBL)-producing isolates of Escherichia coli (EC) were collected from in-patients and their environment at the Zou-Collines Hospital Centre (CHDZ/C) in Benin. The aim of this study was to determine the incidence of ESBL and to describe their phenotypic susceptibility to antibiotics in a secondary hospital (500 beds) in Benin. METHODS: From 15 May to 15 November 2005, clinical informations and samples were collected from patients suspected to have nosocomial infections. The isolates were identified, tested for antimicrobial susceptibility and analysed for the presence of ESBL genes blaTEM and blaSHV by PCR. RESULTS: One hundred ninety-seven enterobacteria were isolated from the clinical samples of 342 patients, these isolates included 143 EC and 32/143 (22%) of these isolates produced ESBL. Forty-six EC were isolated from the environment and 7 (15%) of them produced ESBL. Except for Imipenem for which the difference was not significant, the isolates producing ESBL were more resistant to the other antibiotics (especially to third generation cephalosporins: Ceftriaxone, Cefotaxime, Ceftazidime (P<0.00001)) than non-ESBL producing isolates. Both ESBL genes blaSHV and blaTEM were identified in the EC ESBL strains from patient and from the environment. CONCLUSION: This study shows the presence of ESBL genes among EC in various wards of the CHDZ/C hospital proving that there is a need to implement a strict hospital infection control program and a regular surveillance of resistance to antimicrobial agents.     

Effect of vitamin A supplementation on measles-specific antibody levels in Guinea-Bissau

We have previously reported that vitamin A supplementation with measles vaccine at age 9 months increases measles-specific antibody concentrations in children at age 18 months compared with placebo. We examined these children when they reached age 6-8 years. Fewer vitamin A-supplemented children had non-protective antibody concentrations (p=0.0095); among children with protective antibody levels, vitamin A-supplemented children tended to have higher geometric mean antibody titres (p=0.09). Thus, simultaneous administration of vitamin A and measles vaccine at age 9 months had a long-term effect on measles-specific antibody levels and may contribute to improved measles control in less-developed countries.