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Named one of the \"Ten must-read science histories\" by Science Magazine In a lifetime of practice, most physicians will never encounter a single case of PKU. Yet every physician in the industrialized world learns about the disease in medical school and, since the early 1960s, the newborn heel stick test for PKU has been mandatory in many countries. Diane B. Paul and Jeffrey P. Brosco's beautifully written book explains this paradox. PKU (phenylketonuria) is a genetic disorder that causes severe cognitive impairment if it is not detected and treated with a strict and difficult diet. Programs to detect PKU and start treatment early are deservedly considered a public health success story. Some have traded on this success to urge expanded newborn screening, defend basic research in genetics, and confront proponents of genetic determinism. In this context, treatment for PKU is typically represented as a simple matter of adhering to a low-phenylalanine diet. In reality, the challenges of living with PKU are daunting. In this first general history of PKU, a historian and a pediatrician explore how a rare genetic disease became the object of an unprecedented system for routine testing. The PKU Paradox is informed by interviews with scientists, clinicians, policymakers, and individuals who live with the disease. The questions it raises touch on ongoing controversies about newborn screening and what happens to blood samples collected at birth.

Background. Dietary plant sterols, especially sitostanol, reduce serum cholesterol by inhibiting cholesterol absorption. Soluble sitostanol may be more effective than a less soluble preparation. We tested the tolerability and cholesterol-lowering effect of margarine containing sitostanol ester in a population with mild hypercholesterolemia. Methods. We conducted a one-year, randomized, double-blind study in 153 randomly selected subjects with mild hypercholesterolemia. Fifty-one consumed margarine without sitostanol ester (the control group), and 102 consumed margarine containing sitostanol ester (1.8 or 2.6 g of sitostanol per day). Results. The margarine containing sitostanol ester was well tolerated. The mean one-year reduction in serum cholesterol was 10.2 percent in the sitostanol group, as compared with an increase of 0.1 percent in the control group. The difference in the change in serum cholesterol concentration between the two groups was -24 mg per deciliter (95 percent confidence interval, -17 to -32; P0.001). The respective reductions in low-density lipoprotein (LDL) cholesterol were 14.1 percent in the sitostanol group and 1.1 percent in the control group. The difference in the change in LDL cholesterol concentration between the two groups was -21 mg per deciliter (95 percent confidence interval, -14 to -29; P0.001). Neither serum triglyceride nor high-density lipoprotein cholesterol concentrations were affected by sitostanol. Serum campesterol, a dietary plant sterol whose levels reflect cholesterol absorption, was decreased by 36 percent in the sitostanol group, and the reduction was directly correlated with the reduction in total cholesterol (r

Management of dyslipidemia in adults with diabetes. S M Haffner Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7873, USA. Abstract Subjects with diabetes have a greatly increased risk of CHD, which is only partially related to their elevated glucose. Other factors such as insulin resistance and dyslipidemia are likely to be important. The type of dyslipidemia that is most characteristic of type 2 diabetic subjects is elevated triglycerides and decreased HDL cholesterol levels, although all lipoproteins have compositional abnormalities. Surprisingly few good prospective studies of lipoprotein levels in relation to CHD have been done in diabetic subjects. Available studies suggest that low HDL cholesterol may be the most important risk factor for CHD in observational studies. In studies in which total cholesterol and triglyceride were done, cholesterol and triglycerides were risk factors for CHD, although triglycerides were often a stronger predictor. However, the strength of triglyceride as a risk factor for CHD may depend partially on its association with other variables (e.g., hypertension, plasminogen activator inhibitor 1 [PAI-1], etc.). In clinical trials in diabetic subjects, LDL reduction with statins has led to significant reductions in CHD incidence. In addition, overall mortality was reduced with statin therapy, although the results were not statistically significant. Gemfibrozil has led to reductions in CHD incidence in diabetic subjects, although the results were not statistically significant perhaps because of low sample size. Regarding lipoproteins and CHD risk in diabetic patients, the very positive results of statin trials point to LDL cholesterol being more important than previous realized. Apparently, having a borderline high LDL cholesterol (between 130 and 160 mg/dl) in a diabetic patient is equivalent to a much higher LDL cholesterol in terms of CHD risk for a nondiabetic subject. Therefore, the primary target of therapy in diabetic patients is lowering LDL cholesterol (or possibly, non-HDL cholesterol). Statins are the preferred pharmacological agent in this situation. Once LDL cholesterol levels have been lowered, attention can be given to treatment of residual hypertriglyceridemia and low HDL. The goal here is weight reduction and increased exercise. However, for selected patients, combining a fibric acid (or low-dose nicotinic acid) with a statin also can be considered. Reduction of LDL levels should take priority over reduction of triglycerides in combined hyperlipidemia because of the proven safety of the statin class of drugs as well as greater reduction in CHD incidence.

:  To assess the effect of a seaweed mixture on lipid levels in serum as well as platelet aggregation in rats, Eisenia bicyclis (‘Arame’), Hizikia fusiformis (‘Hijiki’) and Undaria pinnatifida sporophylls (‘Mekabu’), all brown seaweeds, and Porphyra yezoensis (‘Susabinori’), a red seaweed, were powdered and mixed in a ratio of 45:30:20:5 (w/w). When rats were fed a cholesterol‐rich diet containing this mixture of seaweeds (9–10% w/w) for 28 days, serum total cholesterol, LDL‐cholesterol, free cholesterol, and triglyceride levels declined significantly to 49.7%, 48.1%, 49.0% and 74.8%, respectively, of those of the control. Serum HDL‐cholesterol, however, was unchanged. Though activated partial thromboplatin time, prothrombin time, antithrombin III activity, and fibrinogen levels in plasma were unchanged, the maximal ADP‐ and collagen‐induced platelet aggregation decreased significantly to 89.0% and 85.5% control levels, respectively. These results indicate that this mixture of E. bicyclis, H. fusiformis, U. pinnatifida sporophylls, and P. yezoensis, is useful for the prevention of hyperlipidemia and thrombosis in rats.

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Conflicting results have been reported concerning its role in atherogenesis. To determine the effects of the overexpressed LPL on diet-induced atherosclerosis, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpressed human LPL transgene (LPL/LDLRKO) and compared their plasma lipoproteins and atherosclerosis with those in nonexpressing LDLR-knockout mice (LDLRKO). On a normal chow diet, LPL/LDLRKO mice showed marked suppression of mean plasma triglyceride levels (32 versus 236 mg/dl) and modest decrease in mean cholesterol levels (300 versus 386 mg/dl) as compared with LDLRKO mice. Larger lipoprotein particles of intermediate density lipoprotein (IDL)/LDL were selectively reduced in LPL/LDLRKO mice. On an atherogenic diet, both mice exhibited severe hypercholesterolemia. But, mean plasma cholesterol levels in LPL/LDLRKO mice were still suppressed as compared with that in LDLRKO mice (1357 versus 2187 mg/dl). Marked reduction in a larger subfraction of IDL/LDL, which conceivably corresponds to remnant lipoproteins, was observed in the LPL/LDLRKO mice. LDLRKO mice developed severe fatty streak lesions in the aortic sinus after feeding with the atherogenic diet for 8 weeks. In contrast, mean lesion area in the LPL/LDLRKO mice was 18-fold smaller than that in LDLRKO mice. We suggest that the altered lipoprotein profile, in particular the reduced level of remnant lipoproteins, is mainly responsible for the protection by LPL against atherosclerosis

Diabetes is a disease which induces changes in the metabolism of the whole organism. Alloksan is a compound which damages beta cells of the islets of Langerhans within the pancreas inducing experimental diabetes in animals. The cytotoxic action of alloksan can affect other types of cells leading to their injuries. The known treatment of diabetes has not resulted in its total cure so far. Numerous experiments are carried out in order to find substances of preventive effect as well as substances which can relieve the negative impact of this disease. In this study the effect of iscador the substances of wide-range antioxidative and immunostimulating action on selected metabolic parameters during the course of diabetes in mice is presented. The experiments were carried out on male mice, average body weight 25 – 26g, bred in the constant light conditions LD 12:12 and fed with standard diet with unlimited access to water. The concentration of glucose, cholesterol and triglycerides was estimated in the blood serum with STAMAR kits. The statistical analysis of the results was carried out with Statistica program version 8. The results indicate that the application of iscador reduced glucose concentration, cholesterol and triglyceride concentrations in blood serum of mice with induced experimental diabetes.

The effect of cabbage extract on cholesterol metabolism was studied in Donryu rats subcutaneously implanted with an ascites hepatoma cell line (AH109A). The hepatoma‐bearing rats exhibited hypercholesterolemia induced by increasing cholesterogenesis in the host liver and decreasing steroid excretion into feces. The cabbage extract intake or administration reduced serum cholesterol level and enhanced fecal bile acid excretion and cholesterol 7α‐hydroxylase activity, the rate‐limiting enzyme of bile acid biosynthesis, in the microsomal fraction of the liver. Furthermore, S‐methyl‐l‐cysteine sulfoxide, a component of cabbage, could mimic the effect of cabbage extract when orally administered. These results suggest that cabbage suppresses hypercholesterolemia responding to hepatoma growth by upregulating cholesterol catabolism and that S‐methyl‐l‐cysteine sulfoxide in cabbage is one of the factors suppressing hypercholesterolemia in the hepatoma‐bearing rats.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were distributed mainly in the sn‐1,3 positions of seal oil triglyceride and in the sn‐2 position of squid oil triglyceride. Seal oil‐rich or squid oil‐rich fats having constant saturated/monounsaturated/polyunsaturated fatty acid (PUFA) and n−6/n−3 PUFA ratios were fed to exogenously hypercholesterolemic rats for 160 d. The control fat contained linoleic acid as the sole PUFA. Before starting the experimental diets, rats were orally treated with high doses of vitamin D for 4 d to accelerate atherogenesis. The percentage of arachidonic acid in phosphatidylcholine and phosphatidylethanolamine of liver, platelets, and aorta was lower in the marine oil groups than in the control group, seal oil being more effective than squid oil. Maximal platelet aggregation induced by collagen was significantly lower both marine oil groups. Platelet thromboxane (TX) A2 production induced by collagen or thrombin was markedly reduced by feeding seal or squid oils, the reduction being more pronounced in the seal oil than in the squid oil group. Aortic prostacyclin (PGI2) production was the same among the three groups. The ratio of the productions of aortic PGI2 and platelet TXA2 was significantly higher in the seal oil than in the control group. Although there was no difference in intimal thickness among the three groups, the aortic cholesterol content was significantly lower in the marine oil groups than in the control group. These results showed that the main effects in rats of the different intramolecular distributions of EPA and DHA in dietary fats were on arachidonic acid content in tissue phospholipids and on platelet TXA2 production.

Dysfunction of pancreatic islets plays a crucial role in the etiology of type II diabetes. Chronic hyperglycaemia or hyperlipidaemia may impair islet function. Previous studies by our laboratory have demonstrated that dopaminergic agonists ameliorated hyperglycaemia and hyperlipidaemia in obese and diabetic rodents. In the present study, we investigated the effect of a treatment with the dopamine D2/D1 receptor agonists (bromocriptine/SKF38393, BC/SKF) on islet dysfunction in db/db mice. Our results show that a 2-week BC/SKF treatment markedly reduced hyperglycaemia and hyperlipidaemia, and significantly improved islet dysfunction demonstrated by an increase of secretagogue-stimulated insulin release from islets of db/db mice to levels observed in islets from lean mice. There was also a fourfold increase of insulin content in the pancreas of BC/SKF-treated db/db mice compared with that in untreated controls. The effect of BC/SKF on islet function cannot be mimicked in pair-fed animals. BC/SKF had no direct stimulatory effect on islet insulin secretion, suggesting BC/SKF treatment improved islet function via an indirect mechanism. This treatment markedly improved the abnormally elevated daily levels of corticosterone, blood glucose and plasma lipids, supporting the view that BC/SKF may affect the neuroendocrine system that in turn regulates peripheral metabolism and thereby improves islet function.

The Swedish Obese Subjects Study followed obese subjects treated with gastric surgery and contemporaneously matched, conventionally treated obese controls. Surgically treated subjects who were enrolled for at least 2 years (4047 subjects) or 10 years (1703 subjects) had a lower incidence of diabetes, hypertriglyceridemia, and hyperuricemia; differences in the incidence of hypercholesterolemia and hypertension were not significant. Bariatric surgery appears to be a viable option in the treatment of severe obesity, resulting in long-term weight loss, improved lifestyle, and amelioration of some risk factors. Obesity is associated with increased morbidity and mortality. 1 The increased morbidity is assumed to be mediated mainly by insulin resistance, diabetes, hypertension, and lipid disturbances — conditions that affect one quarter of the North American population. 2 , 3 Over the short term (one to three years), lifestyle changes resulting in weight loss result in improvements in insulin resistance, 4 diabetes, 5 – 7 hypertension, 8 and lipid disturbances 9 – 11 or in the prevention of these conditions. In contrast, several (but not all 12 ) observational epidemiologic studies have suggested that weight loss is associated with increased overall mortality and mortality from cardiovascular causes, not only among . . .