Effects of Recombinant Human Lecithin Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans.

BACKGROUND: LCAT (lecithin cholesterol acyl transferase) catalyzes the conversion of unesterified, or free cholesterol, to cholesteryl ester, which moves from the surface of HDL (high-density lipoprotein) into the neutral lipid core. As this iterative process continues, nascent lipid-poor HDL is converted to a series of larger, spherical cholesteryl ester-enriched HDL particles that can be cleared by the liver in a process that has been termed reverse cholesterol transport. METHODS: We conducted a randomized, placebocontrolled, crossover study in 5 volunteers with atherosclerotic cardiovascular disease, to examine the effects of an acute increase of recombinant human (rh) LCAT via intravenous administration (300-mg loading dose followed by 150 mg at 48 hours) on the in vivo metabolism of HDL APO (apolipoprotein)A1 and APOA2, and the APOB100-lipoproteins, very low density, intermediate density, and low-density lipoproteins. RESULTS: As expected, recombinant human LCAT treatment significantly increased HDL-cholesterol (34.9 mg/dL; P≤0.001), and this was mostly due to the increase in cholesteryl ester content (33.0 mg/dL; P=0.014). This change did not affect the fractional clearance or production rates of HDL-APOA1 and HDL-APOA2. There were also no significant changes in the metabolism of APOB100-lipoproteins. CONCLUSIONS: Our results suggest that an acute increase in LCAT activity drives greater flux of cholesteryl ester through the reverse cholesterol transport pathway without significantly altering the clearance and production of the main HDL proteins and without affecting the metabolism of APOB100-lipoproteins. Long-term elevations of LCAT might, therefore, have beneficial effects on total body cholesterol balance and atherogenesis.

Dynamic regulation of hepatic lipid metabolism by torsinA and its activators.

Depletion of torsinA from hepatocytes leads to reduced liver triglyceride secretion and marked hepatic steatosis. TorsinA is an atypical ATPase that lacks intrinsic activity unless it is bound to its activator, lamina-associated polypeptide 1 (LAP1) or luminal domain-like LAP1 (LULL1). We previously demonstrated that depletion of LAP1 from hepatocytes has more modest effects on liver triglyceride secretion and steatosis development than depletion of torsinA. We now show that depletion of LULL1 alone does not significantly decrease triglyceride secretion or cause steatosis. However, simultaneous depletion of both LAP1 and LULL1 leads to defective triglyceride secretion and marked steatosis similar to that observed with depletion of torsinA. Depletion of both LAP1 and torsinA from hepatocytes generated phenotypes similar to those observed with only torsinA depletion, implying that the 2 proteins act in the same pathway in liver lipid metabolism. Our results demonstrate that torsinA and its activators dynamically regulate hepatic lipid metabolism.

No-scalpel vasectomy: review of the first 1,000 cases in a family medicine unit

In Mexico, the Mexican Institute of Social Security (IMSS) had adopted the no-scalpel vasectomy technique by the end of 1989. The technique was described by dr. Li Shunquiang in 1974, and more than 60 million no-scalpel vasectomies have been performed in 26 countries. Among the advantages with no-scalpel vasectomy is that it has fewer complications (0.4 percent) compared to the traditional technique (3.1 percent). We studied 1,00o clinical chart of the subjects operated on between January, 1990 and January, 1993, with the objective of reporting our experiences as well as analyzing whether there existed a correlation between the subject's social and demographic characteristics and the number of control spermatic counts he attended postoperatively. In 97.9 percent of the cases, subjects has no postoperative hemorrhage or hematoma. None of the subjects had a surgical woun infection. In addition, 54.4 percent of the subjects came to the first control spermatic count, 39.7 percent came to the second, and only 18.4 percent came to all three controls. In an attempt to find a characteristic which defined the subject who attends his postoperative control spermatic count, we found an association using X² between the attendance at two controls with the subjects who had been married from 6 - 10 years (p=0.059), and with the subjects who had an income of three minimun wages. Regarding the attendance at all three controls, we found an association with subjects who had an income of two minimun wages (p=0.037). We also found a weak correlation between the attendance at all three controls and the reason reported for not having more children (the couple did not want more children) (r=0.07; p=0.025) and with the manner in which the subjects were referred to the clinic (came on their own initiative) (r=0.09; p=0.006). Finally, we consider that no-scalpel vasectomy can be implemented as an adequate family planning mehtod in Mexico's primary care centers. The lack of adequate attendance at postoperative control spermatic counts does not seem to have an important association with the subjects demographic characteristics, so it appears warranted that this issue be studied from a psychological point of view