ABSTRACT
OBJECTIVE: The liver is the major site of apolipoprotein(a) synthesis, and an inverse correlation between the size of apolipoprotein(a) isoforms and its serum levels have been described. We evaluated the Apo(a) serum levels and its isoforms in patients with liver cirrhosis at different stages of the disease (Childe Turcotte classification), and during the characteristic phase of liver synthesis decline. METHODS: We studied 84 patients with liver cirrhosis and 185 control subjects with normal liver function. RESULTS: Apo(a) serum levels were significantly lower (p < 0.01) in cirrhotic patients and, after 24 months, six patients showing a change from class A to class B had a statistically significant decrease in Apo(a) concentrations (p = 0.0313). Moreover, our data showed an inversion of the small/large isoforms ratio in patient with cirrhosis in spite of the reduction in plasma concentration. CONCLUSION: We showed a reduction of Apo(a) serum concentrations in a large number of patients with cirrhosis and, for the first time, during the characteristic phase of liver synthesis decline, confirming the liver as the major site of Apolipoprotein(a) synthesis. Moreover we showed in the cirrhotic patients that the normal correlation between Apo(a) isoforms and Apo(a) concentrations is not conserved and the low levels are not dependent upon a high prevalence of large isoforms.
Subject(s)
Apolipoproteins A/blood , Apolipoproteins A/classification , Liver Cirrhosis/blood , Apolipoproteins A/metabolism , Female , Follow-Up Studies , Genotype , Humans , Liver/metabolism , Liver Function Tests , Male , Middle AgedABSTRACT
OBJECTIVE: To study the long-term effects of simvastatin on urinary albumin excretion rate (AER) in normotensive microalbuminuric type 2 diabetic patients with hypercholesterolemia. RESEARCH DESIGN AND METHODS: A total of 19 normotensive microalbuminuric hypercholesterolemic type 2 diabetic patients entered a double-blind crossover study for 2 years, receiving either simvastatin (20 mg/day) or placebo (each treatment for 1 year). RESULTS: Simvastatin significantly decreased plasma cholesterol (total and LDL) after 52 weeks of treatment. A concomitant significant decrease of AER (25% from basal) with no significant changes in creatinine clearance was observed during the same period. CONCLUSIONS: Our data are in keeping with the hypothesis that simvastatin might be used as an additional means to preserve renal function in microalbuminuric hypercholesterolemic type 2 diabetic patients.
Subject(s)
Albuminuria/urine , Anticholesteremic Agents/therapeutic use , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/urine , Hypercholesterolemia/drug therapy , Simvastatin/therapeutic use , Adult , Aged , Albuminuria/complications , Albuminuria/metabolism , Cross-Over Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/etiology , Diabetic Nephropathies/metabolism , Double-Blind Method , Female , Humans , Hypercholesterolemia/complications , Hypercholesterolemia/metabolism , Lipid Metabolism , Lipids/blood , Male , Middle Aged , Time FactorsABSTRACT
The complete nuclear maturation and fertilization in vitro of oocytes from 30-40-day-old juvenile lambs, and their ability to develop up to the blastocyst stage when transferred into recipient ewes after fertilization in vivo and culture was studied. Cumulus-oocyte complexes were recovered from juvenile ovaries and only those with several cumulus cell layers were selected and compared with oocytes from adult sheep. The rate of meiotic progression was significantly lower (P < 0.001) for juvenile oocytes (8%) than for adult oocytes (58%) without gonadotrophins in the culture medium. However, a similar maturation rate was observed in oocytes of both juvenile (76%) and adult sheep (84%) in the presence of gonadotrophins. Eighteen hours after in vitro insemination, the fertilization rates for juvenile oocytes were not significantly different from those of adult oocytes (64% and 72%, respectively). Parthenogenetic activation and polyspermy were higher in juvenile than in adult oocytes (P < 0.001). The proportion of blastocysts produced was lower for juvenile (20%) than for in vitro matured adult oocytes (49%) after their transfer into transitory recipients for 5.5 days (P < 0.01). However, the viability of blastocysts (67%) derived from in vitro matured juvenile oocytes showed a rate of hatching similar to that obtained from adult oocytes (74%). Pregnancy rates for recipient ewes at 90 days were similar for both juvenile (57%) and adult (61%) oocytes. The results indicate that it is possible to mature and fertilize in vitro matured juvenile oocytes to produce viable embryos.
