Ciprofibrate--racemate and enantiomers: effects of a four-week treatment on male inbred Fischer rats. A biochemical and morphological study

Ciprofibrates (racemate and both enantiomers, Raccip, R- and Scip) were administered orally in doses of 1 and 10 mg/kg once daily over 28 days to male inbred Fischer 344 rats, age 90-110 days at the beginning of the experiment. Body mass gain was observed in all groups. The 1 mg groups showed almost no difference to the control group. The 10 mg groups exhibited less body mass gain, most pronounced in the Scip group. Liver masses were increased in a dose dependent manner up to more than 200%, only the 10 mg Scip group was not significantly different from the 1 mg group which exhibited an increase in liver weight to about 175%. Also the kidney weights increased to 130%, whereas thymus and spleen weights were decreased in the high dose groups. Liver microsomal cytochromes P450 (P450) concentrations were not altered in the 1 mg groups and distinctly lowered in the 10 mg groups. Ethoxyresorufin and ethoxycoumarin O-deethylations were lowered in all experimental groups in a dose dependent manner, after administration of the high doses down to 30% of the control levels or less. Pentoxyresorufin O-depentylation, however, was increased in all 1 mg groups. In the high dose groups it was not altered. Ethylmorphine N-demethylation was decreased after administration of the high doses by about 50%, but only Scip decreased this reaction also after administration of the low dose. NADPH/Fe2+-stimulated microsomal luminol and lucigenin amplified chemiluminescence was increased, whereas hydrogen peroxide formation was depressed even by the low doses to 50% of the normal values, to about 25% by the high doses. Microsomal lipid peroxidation, however, was only slightly or not influenced. Glutathion concentrations (in the reduced and the oxidized form) were increased in a dose dependent manner by about 20 to 30%, the concentration of lipid peroxides was not significantly influenced. Thus, the effects of the enantiomers were not different and were similar to those of the racemate. In serum, cholesterol and triglycerides were only moderately lowered. Albumin concentrations were significantly enhanced in all groups, total proteins after 1 mg/kg Raccip only. Serum bilirubins were not altered, and among the indicator enzymes for liver damage only ALAT, alkaline phosphatase and the dehydrogenases were increased, in no case higher than twofold. Histologically distinct effects were seen after administration of both doses, more pronounced after 10 mg/kg, but with no differences between the enantiomers and Raccip: marked hypertrophy of the hepatocytes, reduced staining of the nuclei, strongly acidophilic granulated cytoplama, no basophilia of the cell bodies, loss of glycogen. These changes were most pronounced around the central veins. Hepatocyte apoptoses also were observed. By immunohistochemistry an increased staining was seen for all P450 isoforms tested (1A1, 2B1, 2E1, 3A2 and 4A1), predominantly perivenously and most pronounced after administration of the high doses without differences between Rcip, Scip or Raccip (preliminary results). By electron microscopy a moderate proliferation of peroxisomes after treatment with 1 mg/kg Cips with a ratio between mitochondria and peroxisomes of about 1:1 (controls: 10:1) was observed, and the peroxisomes were a more heterogeneous population. The relative portions of glycogen and both forms of the ER decreased. Treatment with 10 mg/kg Rcip, Scip or Raccip led to a strong increase in the number of peroxisomes, in some hepatocytes the ratio between mitochondria and peroxisomes was 1:3 with an increased heterogeneity among the peroxisomes evidenced by a broad range of electron densities. Most peroxisomes lacked a nucleoid. Thus, the biochemical effects differed only slightly and the morphological effects of the enantiomers were not different and were similar to those of the racemate.     

Are weaning foods causing impaired iron and zinc status in 1-year-old Swedish infants? A cohort study

Retrobulbar hematoma is a rare complication of blunt periorbital trauma with the potential disastrous consequence of visual impairment and blindness. The preoperative assessment, diagnostic symptoms and signs, as well as the treatment of this condition are reviewed. The patients presented as well as a review of the literature confirm that although retrobulbar hematoma is a rare complication of blunt periorbital trauma, irreversible visual sequelae can be prevented by prompt diagnosis and immediate surgical and pharmacological therapy.     

Diagnosis of hemostasis disorders in young children using turbidimetry

Practical application of turbidimetrical method for the diagnosis of haemostasis disorders in babies with acute intestinal infections (AII) is described. The results of plasma biochemical analysis show that disturbances in balance between coagulation and fibrinolytic systems takes place in patients with this pathology. The correlation between biochemical parameters and clinical characteristics is observed. As follows from our data, the phase of the haemostasis disorders in babies with AII does not depend on etiology of the disease, but indicates its severity.     

Overexpression of amyloid precursor protein of Alzheimer's type in brains of intoxicated children

The coincidence of neuronal stress induced by intoxication and an overexpression of amyloid precursor protein (APP) in the brains of children was examined. Brains of ten children accidentally intoxicated by poisonous mushroom were studied by means of immunohistochemical methods using monoclonal antibodies generated against different domains of APP and glial cell markers. Overexpression of APP was found in the brain neurons of all intoxicated children. Neurons were immunopositive with the antibodies generated against the middle (amyloid beta protein) domain of APP. No extracellular deposits were found in the tissue. Our results provided, for the first time, the evidence that overexpression of APP concomitant with the neuronal stress is age-independent phenomenon appearing not only in the brain of adults but in very young individuals as well.     

Endometrial and fetoplacental markers in pregnancies with fetal congenital nephrosis

BACKGROUND: Interview studies which employ qualitative methodology are often concerned with classifying behaviours or attitudes and an ideal sample of research subjects displays variety in the attitudes or behaviours under scrutiny. OBJECTIVE: This paper describes the development of a questionnaire which measures GPs' attitudes towards discussing smoking with patients with the intention of using this instrument to select GPs with diverse views for a qualitative interview study. METHOD: Thirteen attitude statements with an accompanying Likert-type scale were completed by 327 GPs in one FHSA area. Factor analysis of responses produced two subscales: 'perceived efficacy' and 'enthusiasm'. Reliability and validity of these were examined. RESULTS: Each subscale had good internal reliability and preliminary exploration of construct validity supported the notion that the subscales were valid. CONCLUSION: The use of this type of instrument in sampling GPs for qualitative studies could be effective for selecting subjects with a diversity of views towards the research topic.     

Indomethacin reduces contraction of isolated non-pregnant human uterine artery induced by prostaglandin F2 alpha

The purpose of this study was to explore whether cyclooxygenase products derived from endothelium or vascular smooth muscle participate in the response of human uterine artery to prostaglandin F2 alpha. Experiments were performed using human uterine arterial rings. Prostaglandin F2 alpha (0.4 nM-1 microM) induced contraction of human uterine arteries with both intact and denuded endothelium with similar potency and efficacy (pD2 values: 7.93 +/- 0.01 and 8.07 +/- 0.03 for vessels with and without endothelium respectively; maximal response values: 89.1 +/- 4.7% and 92.3 +/- 3.8% for vessels with and without endothelium respectively). Indomethacin (10 microM) significantly suppressed the maximum effects of prostaglandin F2 alpha and induced a shift towards the right of the prostaglandin F2 alpha concentration-response curves, regardless of the endothelial condition. On the other hand, in both types of preparations, OKY-046 (10 microM), an inhibitor of thromboxane synthesis, did not affect prostaglandin F2 alpha-induced contraction of human uterine arteries. It is concluded that in human uterine artery prostaglandin F2 alpha-induced contraction is mediated, at least in part, through constrictor prostanoid(s) of vascular smooth muscle origin that is not thromboxane A2.     

The effect of duration of endemic nephropathy on serum angiotensin converting enzyme activity

The effects of duration of disease on serum angiotensin converting enzyme (ACE) was measured in 60 patients with endemic nephropathy (30 men and 30 women) of age between 30 and 60 years. There were formed three groups: patients with endemic nephropathy and duration of disease less than 5 years (n = 23), patients with endemic nephropathy and duration of disease between 5-10 years (n = 17); and patients with endemic nephropathy and duration of disease 10 years and more (n = 20). The serum ACE activity was determined by the spectrophotometric method using Hip-Gly-Gly as a substrate. The activity of enzyme were expressed in units corresponding to 1 nmol of the hippuric acid that was released by the hydrolysis of Hip-Gly-Gly per minute and ml of serum. The results showed that serum ACE activity decreased in group of patients with endemic nephropathy and duration of disease 10 years and more (29.21 +/- 2.25; X +/- SEM) in comparison with group of patients with endemic nephropathy and the duration of disease less than 5 years (35.57 +/- 1.75), which was statistically significant (p < 0.03).