Controlled substitution with blood products in hemostatic disorders

It is essential for an efficient substitution to define the nature of the defect as good as possible. Simple screening tests allow a rapid classification. Prophylactic substitution is recommended in potentially reversible defects (bone marrow aplasia in connection with leukaemia treatment) and/or imminent bleeding (eventually complicated by additional risk factors). If bleeding cannot be stopped surgically therapeutic substitution is indicated. In case of bone marrow failure, a substitution may be particularly promising. In presence of an increased peripheral platelet destruction (disseminated intravascular coagulation, antithrombocytic antibodies) treatment of the basic disease is mandatory. Combined hemostatic defects can be influenced by fresh frozen plasma (FFP). Fresh whole blood (not older than 48 hours) may be considered in cases of thrombocytopenia and concomitant anemia. For isolated defects (e.g. hemophilias with or without antibodies, congenital afibrinogenemia, lack of factor XIII) special preparations are at hand. The clinical effect of substitution depends on the specific activity of the preparation, on the volume of expansion in the recipient and on other pharmacokinetic factors. Hepatitis and antibody-production may be considered as particularly grave side-effects.     

Assessment of in vivo oxidative lipid metabolism following acute microcystin-LR-induced hepatotoxicity in rats

Oxidative lipid metabolism as a result of acute cyanobacterial toxin-induced hepatotoxicity was monitored in male Sprague-Dawley rats using electron spin resonance (ESR) spectroscopy and image-guided proton nuclear magnetic resonance (1H-NMR) spectroscopy. ESR spectroscopy, coupled with spin trapping, was used to trap and detect lipid-derived radicals, formed in rat livers after acute in vivo exposure (LD50) to the cyanobacterial toxin, microcystin-LR (MCLR). A statistically significant increase in the levels (spectral peak integrals) of lipid radicals was detected in MCLR-treated livers (p < 0.05) (n = 8), in comparison to control livers (n = 6). In order to monitor lipid metabolism, before and for a period of 3 h, following toxin exposure, in vivo proton image-guided NMR spectroscopy was used. A statistically significant decrease in the levels of lipid methylene hydrogen resonances (spectral peak integrals) was observed from MCLR-treated livers (n = 6) 2 and 3 h post-exposure (p < 0.05), in comparison to controls (n = 6). Image-guided NMR spectroscopy was also used to detect significant decreasing levels of in vivo glutamine/glutamate, following exposure to MCLR. Biochemical assessment of perchloric extracts of liver glutamine and glutamate levels correlated with NMR spectroscopy results. Lactate levels measured as perchloric acid extracts, were also found to significantly decrease. In addition, assessment of serum enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were used to confirm hepatotoxicity (n = 20). This study strongly suggests that oxidative stress related processes are involved in in vivo microcystin-induced hepatotoxicity in mammals, and may play an integral role in MCLR-induced toxicity.     

In vivo and in vitro effects of prolactin and growth hormone on lipid metabolism in a teleost, Anabas testudineus (Bloch)

Prolactin (PRL) has an important role in the regulation of water and electrolyte homeostasis in teleosts. The present study was designed to evaluate the role of PRL and GH on malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PDH) and isocitrate dehydrogenase (ICDH) in Anabas testudineus. Ovine prolactin significantly inhibited ME, G6PDH and ICDH activities when administered in vivo compared to vehicle treated controls. In vivo administration of PRL reversed the action of bromocryptine on enzyme activities. Ovine growth hormone in vivo also modified the effect of bromocryptine but not to the level of prolactin. Combined action of PRL+GH in vivo was most effective in keeping the enzyme activities at normal level after bromocryptine treatment. Prolactin in vitro also reversed the action of bromocryptine on enzyme activities, while GH in vitro failed to do so. Hence, prolactin seems to have an inhibitory effect on lipid metabolism in this teleost. Combined action of PRL+GH is more prominent in in vivo conditions at low PRL levels. Dopaminergic pathways may be involved in the control of prolactin and to some extent on growth hormone secretion.     

Oxytocin action: lipid metabolism in adipocytes from homozygous diabetes insipidus rats (Brattleboro strain)

Oxytocin, like insulin, stimulates glucose oxidation in normal rat adipocytes. Fat cells from homozygous Brattleboro rats that exhibit diabetes insipidus (HoDI animals) and that have a normal number of oxytocin receptors, however, are unable to respond to oxytocin in terms of glucose oxidation. We now report that in adipocytes from HoDI animals that are responsive to insulin, oxytocin was also unable to stimulate lipogenesis. In contrast, oxytocin like insulin was able to inhibit epinephrine-stimulated lipolysis in adipocytes from HoDI animals. Thus, in HoDI adipocytes, the results indicate that the receptor-effector system is only partially defective.     

Restriction polymorphism in patients with lipid metabolism disorders and ischemic heart disease

Using the RELP analysis we studied the frequency of X2 allele of apoB gene in three groups of patients: 1) men at the age of 20-59 with lipid metabolism disorders revealed in population inspection of Oktyabrsky district in Moscow; 2) men with ischaemic heart disease and 3) healthy men. It was established that in individuals suffering from type IIa hyperlipidemia the frequency of X2 allele was significantly higher than in healthy donors from Moscow population. Homozygotes for X2 allele of XbaI RELP had 7-9% higher serum cholesterol levels, than homozygotes for X1 allele. The study suggests the X2 allele of the apoB gene to be associated with the development of high plasma cholesterol level. No significant difference in X2 allele frequencies was found between patients with ischaemic heart disease and healthy donors. There was also no association found between cholesterol and triglyceride levels and the presence of X2 allele in this group of patients.     

Lupeol supplementation improves blood pressure and lipid metabolism parameters in stroke-prone spontaneously hypertensive rats

Supplementation with lupeol (0.67 g·kg(-1)) of the AIN-93M-based diet fed for 7 weeks to stroke-prone spontaneously hypertensive rats caused significantly decreased blood pressure as compared with a control group. Urinary 8-hydroxy-2'-deoxyguanosine was significantly lower in the lupeol group. Finally, lupeol suppressed the hepatic mRNA expression levels of the genes involved in triglyceride and cholesterol synthesis.     

Effects of dietary sea squirt (Halocynthia roretzi) on lipid metabolism in rats

The effect of dietary sea squirt ( Halocynthia roretzi) on lipid metabolism in rats was investigated. Rats were fed sea squirt muscle (Experiment 1); sea squirt muscle, defatted sea squirt muscle and its hexane extract (Experiment 2); and whole body sea squirt and its parts as muscle or viscera (Experiment 3). All of the diets contained the same levels of protein (20%) and lipid (7%). In experiment 1, serum total cholesterol (T-Ch), very-low-density lipoprotein plus low-density lipoprotein (VLDL+LDL)-Ch, triglyceride (TG), phospholipid (PL) and nonesterified fatty acid (NEFA) levels were reduced by 20% dietary sea squirt muscle ingestion; steroid excretions into feces were enhanced by the same diet. In experiment 2, serum T-Ch, (VLDL+LDL)-Ch, TG, PL and NEFA levels were significantly reduced and steroid excretions into feces were significantly enhanced by ingestion of the sea squirt muscle hexane extract. Ingestion of defatted sea squirt muscle also reduced these serum lipid levels, but not as much as did that of whole sea squirt muscle. In experiment 3, serum T-Ch and HDL-Ch levels were significantly elevated by the 10% sea squirt viscera ingestion.     

The metabolism of (ureyl-14C)tolbutamide in vitro and in vivo in man

Hepatic microsomal kinetic constants and plasma half-lives and plasma clearances for the metabolism of tolbutamine were measured in the same patients. No significant correlations were found for the seven experiments performed. There was a trend to an inverse correlation between hepatic microsomal cytochrome P-450 content and the plasma clearance. The negative findings suggest a lack of variation in the hepatic drug-metabolizing activities of normal humans.     

Chromogranin A (CgA) - the influence of various factors in vivo and in vitro, and existing disorders on it's concentration in blood

Chromogranin A (CgA) is regarded as a major, nonspecific neuroendocrine tumour (NET) marker. The results of CgA blood concentration, however, may actually be influenced by various factors or coexisting pathological conditions. Among the factors causing a substantial increase of the blood CgA concentration are: treatment with proton-pump inhibitors or H2 -receptor blockers, chronic atrophic gastritis (type A), impaired renal function, prostate cancer and BPH, and rheumatoid arthritis with high level of RF IgM. In addition, the sort of investigated biological material (whether it is serum or plasma) is of importance. There are also many conditions which may have a moderate or little influence on the concentration of CgA, among them are: inflammatory bowel disease (ulcerative colitis and Crohn's disease), deteriorating liver function, untreated essential hypertension, heart failure, hypercortisolism, pregnancy, and, in some subjects, ingestion of a meal. Proper assessment of the CgA results requires detailed knowledge about various factors, drugs, and pathological conditions influencing its concentration in blood.     

Effects of dietary oyster extract on lipid metabolism, blood pressure, and blood glucose in SD rats, hypertensive rats, and diabetic rats

Oyster extract was prepared by hydrolysis of oyster protein with proteases, Aloase (a protease from Bacillus subtilis), and Pancitase (a protease from Aspergillus oryzae). Rats were fed a diet containing 20% casein (the control diet) or 15% casein and 5% oyster extract (the oyster extract diet) as the protein source. The oyster extract diet exerted a significant reduction in serum cholesterol and liver triglyceride concentrations as compared with the control diet in Sprague-Dawley (SD) rats fed cholesterol-supplemented diets for 4 weeks. The activities of cytosolic fatty acid synthase and glucose-6-phosphate dehydrogenase were significantly lower in the oyster extract group than in the control group in the liver of SD rats. Hepatic cholesterol and triglyceride concentrations were significantly lower in spontaneously hypertensive (SH) rats and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, type 2 diabetic rats, fed the oyster extract diet, for 4 weeks and 4 months respectively, than in those fed the control diet in the cholesterol-free diet. Blood pressure was significantly lower in the oyster extract group than in the control group at the 2nd and 4th weeks after the beginning of feeding experimental diets in SH rats. These results suggest that oyster extract prepared by hydrolysis of oyster induces triglyceride-lowering activity in the liver through a decrease in hepatic lipogenesis in SD rats, and that it exerts the antihypertensive effect in SH rats.     

Benzyl isothiocyanate disturbs lipid metabolism in rats in a way independent of its thyroid impact following in vivo long-term treatment and in vitro adipocytes studies

During recent decades, benzyl isothiocyanate (BITC) was examined mainly in terms of its cancer chemopreventive action. Although some research has been conducted on goitrogenic activity of many glucosinolate derivatives, little attention has been paid to the BITC impact on the thyroid gland and lipid metabolism strictly associated with it. Therefore, this research project aimed at expanding our knowledge about how non-physiological doses of BITC (widely used in chemotherapy) influence some hormonal and metabolic (lipid) parameters in in vivo and in vitro experiments. The trial was focused on BITC action on thyroid tissue, liver, as well as white adipocyte tissue, at doses which were previously proved to exert a strong anticancer effect (10 mg/kg body weight in vivo and 1, 10 and 100 μmol/L in in vitro trials, respectively). Two-week oral administration of BITC in in vivo trial affected thyroid gland by decreasing total thyroxine and triiodothyronine. However, the obtained lipid profile was not specific for thyroid hormone deficiency because no lipid changes in the blood serum and liver steatosis were observed. BITC per se evoked elevation of basal lipolysis at 1 and 100 μmol/L and limitation of basal lipogenesis at 100 μmol/L in adipocyte tissues in in vitro experiment. BITC did not remain indifferent to liver metabolism by its possible influence on hepatic cholesterol 7α-hydroxylase and 5-deiodinase as well as on adipocytes by its enhanced basal lipolysis and limited lipogenesis independently of epinephrine and insulin action steps, respectively. Additionally, BITC was probably involved in bile flow obstruction.