Dietary inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women

OBJECTIVE: To determine the effects of dietary inclusion of soy foods on clinical markers for cardiovascular disease (CVD) and osteoporosis in normal postmenopausal women. DESIGN: This was a single open-group prospective clinical intervention. Forty-two normal postmenopausal women consumed three daily servings for 12 consecutive weeks of whole soy foods containing approximately 60 mg/d of isoflavones. Blood and urine specimens were obtained at baseline and after 12 weeks of dietary intervention. RESULTS: Serum and urine levels of individual and total isoflavones increased significantly (7-19 fold, p < 0.001) from baseline. A significant increase (9.3%, p < 0.05) in the mean lag-time of low-density lipoprotein cholesterol oxidation was seen and was positively correlated with serum phytoestrogens (p < 0.05). Significant increases were found in mean levels of high-density lipoprotein cholesterol (HDLc) (3.7%, p < 0.05) and serum osteocalcin (10.2%, p < 0.025). Significant decreases were observed in total cholesterol:HDLc ratios (5.5%, p < 0.006) and mean urinary N-telopeptide excretion (13.9%, p < 0.02). Urinary excretion of total isoflavones was negatively correlated with very-low-density lipoprotein cholesterol, triglycerides, and total cholesterol:HDLc ratios (p < 0.04). No significant changes from baseline in HDLc peroxidation, total cholesterol, triglycerides, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, bone-specific alkaline phosphatase, follicle-stimulating hormone, or estradiol levels were observed. CONCLUSIONS: Dietary inclusion of whole soy foods containing 60 mg/d of isoflavones results in significant serum levels of phytoestrogens and reductions in several key clinical risk factors for CVD and osteoporosis in normal postmenopausal women. Long-term, placebo-controlled clinical trials are needed to evaluate the effect of phytoestrogens on the clinical endpoints of CVD and osteoporosis in this population.     

Effect of omalizumab on adenosine 5'-monophosphate responsiveness in subjects with allergic asthma

BACKGROUND: The objective of this study was to evaluate the effects of omalizumab on bronchoconstriction induced by methacholine and adenosine 5'-monophosphate (AMP). METHODS: Thirty-four subjects with mild to moderate allergic asthma were randomized to receive placebo (n = 16) or omalizumab (n = 18) subcutaneously during 12 weeks. Airway responsiveness to AMP was measured at baseline and after 4 and 12 weeks of treatment, whereas the response to methacholine was measured at baseline and after 12 weeks of treatment. RESULTS: After 4 weeks of treatment, the increase in AMP PC(20) (provocative concentration required to produce a 20% fall in FEV(1)) was significantly greater in the omalizumab group than in the placebo group, the mean difference in the change between the groups being 1.52 doubling concentrations (95% CI, 0.25-2.79, p = 0.02). Compared with baseline, the mean AMP PC(20) values at 12 weeks were increased by 1.91 doubling concentrations with omalizumab (p < 0.001) and 1.01 doubling concentrations with placebo (p = 0.16), but changes were not significantly different between the treatment groups. Changes in methacholine PC(20) values were not significantly different between the omalizumab and placebo groups. CONCLUSIONS: In subjects with allergic asthma, omalizumab reduces the response to AMP without decreasing the response to methacholine. These findings are consistent with the conclusion that the contribution of IgE to the development of AMP bronchoconstriction is more important than their role in the induction of methacholine hyperresponsiveness.     

Effect of soy protein-containing isoflavones on lipoproteins in postmenopausal women

OBJECTIVE: Some clinical trials have demonstrated a beneficial effect of dietary soy protein on improving lipoproteins. Research also has documented that serum lipoproteins and some lipoprotein subclasses are altered as a consequence of menopause, resulting in a more atherogenic lipid profile. The purpose of this study was to determine the effects of isolated soy protein-containing isoflavones on lipoproteins and lipoprotein subclasses in both African American and white postmenopausal women with borderline to moderate low-density lipoprotein cholesterol elevations. DESIGN: This was a randomized, double-blind, controlled clinical trial including 216 postmenopausal women. After a 4-week run-in period with a casein protein-based supplement, participants were randomly assigned to continue the casein placebo or receive soy protein-containing isoflavones for a period of 12 weeks. RESULTS: In the soy group, the total cholesterol, low-density lipoprotein cholesterol, and low-density lipoprotein particle number decreased significantly as compared with the placebo group at 6 weeks. Although this decrease continued at 12 weeks in the soy group, the difference from the placebo group was attenuated for total cholesterol and low-density lipoprotein particle number. Multivariate analyses controlling for age, race, change in weight, change in dietary fat intake, and change in kilocalorie energy expenditure revealed that treatment remained a significant independent predictor of change in total cholesterol (P = 0.01), low-density lipoprotein cholesterol (P = 0.02), and low-density lipoprotein particle number (P = 0.002) after 6 weeks of dietary soy. CONCLUSIONS: Increased consumption of soy protein replacing animal protein that is high in fat may help improve atherogenic lipid profiles.     

Delayed inflammatory responses to endotoxin in fibrinogen-deficient mice

Severe inflammation leads to haemostatic abnormalities, such as the development of microvascular thrombi. As a result, ischaemia-related downstream organ damage can occur. The present study demonstrates that mice with a total deficiency of fibrinogen (Fg(-/-)) present with altered responses to challenge with Gram-negative lipopolysaccharide (LPS). Early survival in response to continuous LPS challenge was increased in Fg(-/-) mice and histological findings indicated that this improvement correlated with a lack of fibrin deposition in organs. Neutrophils appeared early in the lungs of challenged wild-type (WT) mice, but occurred in Fg(-/-) mice at later times. This delayed response in Fg(-/-) mice was confirmed by studies that showed a strong dependence on Fg of binding of neutrophils to endothelial cells in the presence of LPS. While cytokines were also elevated in both WT and Fg(-/-) mice, their levels were generally lower at early times in this latter group. The time course of MIP-2 expression correlated with the occurrence of pulmonary leakage after LPS challenge, which was delayed in Fg(-/-) mice. These results suggest that fibrin(ogen) plays a role as an early mediator in the cross-talk between coagulation and inflammation.     

急性心肌缺血时冠状窦血浆纤维蛋白原的改变及意义

通常人们认为,急性心肌缺血可引起血浆纤维蛋白原(Fg)的增高;但是在缺血区局部Fg的变化并不清楚。本文在17条犬上,以自制微米缩窄器造成冠脉左旋支狭窄与梗塞,观察了冠状窦Fg和血小板数(PC)的改变。结果表明:当冠脉狭窄大于75%后,急性心肌缺血可引起Fg含量的减少,当冠脉大狭窄于90%后,PC也出现减少。病理组织学检查在狭窄部位有内皮细胞的损伤、血小板的粘附及冠状动脉血栓和微血栓的形成。这一结果提示:急性心肌缺血可引起血浆Fg的减少,Fg的减少与血小板的聚集及血栓的形成有关。     

The effects of black cohosh therapies on lipids, fibrinogen, glucose and insulin

OBJECTIVE: Black cohosh (Actaea racemosa) is an herb commonly used to treat menopausal symptoms. Little is known about its effect on other physiologic parameters that could result in untoward events. This study examines the effect of black cohosh on lipids, fibrinogen, glucose and insulin. METHODS: Three hundred and fifty-one, 45-55 years old, peri or post-menopausal women experiencing vasomotor symptoms participated in a 3-month, double blind trial with randomization to: (1) black cohosh (160 mg daily); (2) multibotanical including black cohosh (200 mg daily); (3) multibotanical plus soy diet counseling; (4) conjugated equine estrogen .625 mg, with or without medroxyprogesterone acetate 2.5mg daily, for women with or without a uterus, respectively; (5) placebo. Baseline and month 3 total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol (calculated), triglyceride, insulin, glucose, and fibrinogen serum concentrations were measured in 310 women. Baseline information was also collected on medical history, demographic characteristics, and diet. RESULTS: There were no statistically significant differences in the adjusted mean change from baseline to 3 months between the herbal groups and placebo in total cholesterol, LDL, HDL, triglycerides, glucose, and insulin. Adjusted fibrinogen levels appear to increase in the multibotanical treatment group in comparison with the other herbal groups and placebo overall (P = .02), but there was no statistically significant difference in the pairwise test against placebo (P = .11). CONCLUSIONS: Black cohosh containing therapies had no demonstrable effects on lipids, glucose, insulin or fibrinogen.     

Effect of Hedan Tablets on Body Weight and Insulin Resistance in Patients with Metabolic Syndrome

IntroductionApart from their recognized lipid-lowering effect, Hedan tablets, a mixture of Chinese herbal medicines, have demonstrated a certain weight-loss effect in clinical practice. The aim of this randomized, double-blind, placebo-controlled study was to verify the effect of Hedan tablets on body weight (BW) and insulin resistance (IR) in patients with metabolic syndrome (MetS).MethodsA total of 62 eligible patients with MetS were divided into two groups: the treatment group (Hedan tablets at 4.38 g/day tid) and the control group (placebo treatment). Both groups attended follow-ups at 8, 16, and 24 weeks during the process. The parameters of the assessment include lipid level, BW, triglyceride (TG) to high-density lipoprotein cholesterol (HDLc) ratio (TG/HDLc), homeostasis model assessment for IR (HOMA-IR) index, and adiponectin.ResultsPatients in the treatment group showed a significant decrease in BW compared to those in the control group (−4.47 vs. 0.06 kg) after 8 weeks of treatment. A significant decrease in body mass index (BMI) was also observed in the treatment group after 16 weeks of treatment (−1.79 vs. −0.03 kg/m²). In the treatment group, 20 out of 31 (64.5%) patients lost 5–10% BW and 4 out of 31 (12.9%) patients lost over 10% BW after 24 weeks of treatment. Although there were no significant changes in the patients'' HOMA-IR, the treatment group showed a significant reduction in TG/HDLc (−0.98 vs. −0.19) after 8 weeks of treatment and a significant increase in adiponectin (6.87 vs. −0.43) after 16 weeks of treatment.Discussion/ConclusionThe Hedan tablets significantly improve BW, BMI, TG/HDLc, and adiponectin in patients with MetS. Thus, Hedan tablets may be used as an adjunct to existing MetS management methods.     

The effect of various menopausal hormone therapies on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins in healthy postmenopausal women

OBJECTIVE: Androgenic progestins such as norethisterone acetate (NETA) may influence the effect of estradiol (E(2)) therapy. We compared the influence of oral E(2), with and without NETA, and transdermal E(2) on markers of coagulation, fibrinolysis, and inflammation and on lipids and lipoproteins in healthy postmenopausal women. DESIGN: A total of 112 healthy postmenopausal women were randomized to receive treatment with either oral E(2), with or without NETA, transdermal E(2), or placebo. At baseline and after 28 weeks, levels of serum lipids and lipoproteins and markers of coagulation, fibrinolysis, and inflammation were determined. RESULTS: Of the fibrinolytic parameters, oral E(2) (P < 0.05) and E(2) with NETA (P < 0.01) shortened euglobulin clot lysis time. Oral E(2) decreased plasminogen activator inhibitor-1 activity (P < 0.05). Oral E(2) with NETA reduced plasminogen activator inhibitor-1 antigen levels (P < 0.01) and increased D-dimer antigen levels (P < 0.001). All three modes of menopausal hormone therapy reduced tissue type plasminogen activator antigen. Of the coagulation parameters, both routes of E(2) therapy decreased fibrinogen levels (P = 0.002 for oral and P = 0.007 for transdermal E(2)), whereas E(2) with NETA showed no effect. The decrease of fibrinogen was larger after oral E(2) (P = 0.02). Oral E(2) with NETA reduced antithrombin III (P < 0.001) and protein C (P < 0.001) activity. Oral E(2) (P = 0.04) and E(2) with NETA (P < 0.01) increased C-reactive protein (CRP). Transdermal E(2) showed no influence on CRP. The addition of NETA influenced the change in CRP, as the increase in CRP was more pronounced after E(2) without NETA (P = 0.005). The levels of serum amyloid A, interleukin-6, and tumor necrosis factor-alpha did not change significantly after any of the modes of hormone therapy. Of the lipids and lipoproteins, oral E2 decreased low-density lipoprotein cholesterol (P < 0.01), lipoprotein (a) (P < 0.05), and increased high-density lipoprotein cholesterol (P < 0.05). Transdermal E(2) decreased triglycerides (P < 0.02) and increased high-density lipoprotein cholesterol (P < 0.03). Oral E(2) with NETA decreased total cholesterol (P < 0.01) and high-density lipoprotein cholesterol (P < 0.005). CONCLUSIONS: Oral E(2), with or without NETA, produced no net activation of coagulation but improved fibrinolysis. Both modes of oral menopausal hormone therapy have a greater impact on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins than transdermal E(2). NETA attenuates some E(2) effects. Further studies are needed to elucidate the impact of these effects on clinical endpoints.     

Effect of vitamin E on lipids

A recent clinical report noted that vitamin E administration was followed by a dramatic elevation of high-density lipoprotein cholesterol (HDL-C). Since HDL-C is inversely associated with coronary heart disease, we conducted a randomized, double-blind, placebo-controlled clinical trial of vitamin E administration (800 IU/day) for 16 weeks. The subjects were 30 adults aged 30-60 years, with 15 participants in each group. We measured fasting HDL-C, total cholesterol, and triglycerides at baseline and at 8 and 16 weeks. Vitamin E had no effect on HDL-C; the mean changes at 8 and 16 weeks in the placebo group were -0.3 mg/dL and -2.6 mg/dL, and in the vitamin E group -0.4 and -0.9 mg/dL. Aside from a marginal decrease in calculated low-density lipoprotein cholesterol, at 16 weeks there were no significant differences for any of the lipids. These data, in conjunction with other information in the literature, indicate that vitamin E does not alter plasma lipids in normal adults.     

Oxandrolone in the treatment of HIV-associated weight loss in men: a randomized, double-blind, placebo-controlled study

OBJECTIVE: To evaluate the efficacy and safety of oxandrolone in promoting body weight and body cell mass (BCM) gain in HIV-associated weight loss. METHODS: Randomized, double-blind, placebo-controlled trial. Two hundred sixty-two HIV-infected men with documented 10% to 20% weight loss or body mass index < or =20 kg/m were randomized to placebo or to 20, 40, or 80 mg of oxandrolone daily. After 12 weeks, subjects were allowed to receive open-label oxandrolone at a dose of 20 mg for another 12 weeks. RESULTS: Body weight increased in all groups, including the group receiving placebo, during the double-blind phase (1.1 +/- 2.7, 1.8 +/- 3.9, 2.8 +/- 3.3, and 2.3 +/- 2.9 kg in placebo and 20-, 40-, and 80-mg oxandrolone groups, respectively; all P < 0.014 vs. baseline). BCM increased from baseline in all groups (0.45 +/- 1.7, 0.91 +/- 2.2, 1.5 +/- 2.5, and 1.8 +/- 1.8 kg in placebo and 20-, 40-, and 80-mg oxandrolone groups, respectively). At 12 weeks, only the gain in weight at the 40-mg dose of oxandrolone and the gain in BCM at the 40- and 80-mg doses of oxandrolone were greater than those in the placebo group, however. Oxandrolone treatment was associated with significant suppression of sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, and total and free testosterone levels. Treatment was generally well tolerated but accompanied by significant increases in transaminases and low-density lipoprotein as well as decreases in high-density lipoprotein. CONCLUSION: Oxandrolone administration is effective in promoting dose-dependent gains in body weight and BCM in HIV-infected men with weight loss.     

Dietary sodium restriction: Adverse effect on plasma lipids

Summary In order to examine the effect of dietary sodium intake on plasma lipids, 15 healthy male volunteers were given a low-salt diet (20 mmol/day) for 3 weeks, adding either placebo, sodium chloride (200 mmol/day), or a non-chloride sodium salt (sodium citrate, 200 mmol Na/day) for one week each, in a single-blind randomized crossover study.Plasma levels of total cholesterol and LDL cholesterol were significantly higher at the end of the placebo period than with either sodium chloride (by 8.7 and 11.9%, respectively) (P< 0.005) or sodium citrate (by 11.3% and 16.8%, respectively) (P< 0.005). Thus this effect was dependent on sodium but not on chloride intake. Triglyceride and HDL-cholesterol levels were not affected by the dietary regimens. We conclude that short-term dietary sodium restriction may lead to a rise in plasma total and LDL cholesterol, thereby possibly increasing the risk of atherosclerotic vascular disease. Our findings render it possible that diuretic-induced lipid disturbances may also be caused by sodium depletion.Abbreviations LDL low-density lipoprotein - HDL high-density lipoprotein - CHD coronary heart disease - Ht hematocrit - SEM standard error of mean     

Metalloproteinase-2 and -9 in diabetic and nondiabetic subjects during acute coronary syndromes.

The authors hypothesized that matrix metalloproteinase (MMP)-2, -9, and tissue inhibitor metalloproteinase (TIMP)-1, -2 would be abnormal in acute coronary syndromes (ACSs). MMP-2, -9, and TIMP-1, -2 plasma levels were measured in diabetic patients with ACSs compared to nondiabetic patients with ACSs. A total of 46 diabetic and 78 nondiabetic patients with ACSs were enrolled. The following parameters were measured: body mass index (BMI), glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment index (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct), fibrinogen (Fg), high-sensitivity C-reactive protein (hs-CRP), and plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Significant HbA1c, FPG, FPI, HOMA index, DBP, Tg, Hct, and Fg increases were present in the diabetic group with ACSs, whereas hs-CRP was lower in these patients compared to nondiabetic patients with ACSs. MMP-9, TIMP-1, and TIMP-2 plasma levels were higher in diabetic patients with ACSs compared to nondiabetic patients with ACSs. MMP-9, TIMP-1, and TIMP-2 plasma levels were increased in diabetic patients with ACSs, which may reflect abnormal extracellular matrix metabolism in diabetes during acute event.     

Changes in lipid and lipoprotein profile in postmenopausal women receiving low-dose combinations of 17beta-estradiol and norethisterone acetate

OBJECTIVE: To evaluate the modification of lipid and lipoprotein by use of low doses of continuous-combined formulations of 17beta-estradiol (E ) and norethisterone acetate (NETA) in healthy postmenopausal women. DESIGN: The study was designed as a double-blind, randomized, placebo-controlled trial. A total of 120 healthy postmenopausal women were randomized to one of three treatment arms: (1) placebo group ( = 40); (2) E /NETA 0.25-mg group-subjects receiving oral continuous-combined E 1 mg and NETA 0.25 mg ( = 40); (3) E /NETA 0.5-mg group-women who were treated with E 1 mg and NETA 0.5 mg ( = 40). The duration of study was 12 months. Plasma levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very low-density lipoprotein (VLDL) cholesterol, triglycerides, lipoprotein(a), apolipoprotein A and apolipoprotein B were determined on four occasions (i.e., baseline, 3-, 6-, and 12-month visits). RESULTS: There were no differences in the baseline characteristics among the three groups. A total of 102 women completed the study, resulting in a compliance rate of 85%. There was a significant reduction of total cholesterol, LDL cholesterol, and lipoprotein(a) in both combined groups when compared with placebo. The level of apolipoprotein B declined significantly only in the E /NETA 0.25-mg group. Decrements were observed within 3 months of treatment and maintained thereafter. No significant changes were found in triglycerides, VLDL cholesterol, HDL cholesterol, apolipoprotein A, and LDL/HDL ratio. Between the two active combined groups, no statistically significant differences were noted. CONCLUSION: Favorable changes in lipids and lipoproteins were associated with the low dose of E /NETA combinations. These effects may contribute to the reduction or prevention of atherogenesis in postmenopausal women.     

Effects of soy isoflavones on endothelial function in healthy postmenopausal women

OBJECTIVE: To evaluate the effects of soy isoflavone administration on endothelial function in healthy postmenopausal women. DESIGN: Sixty naturally postmenopausal women were randomly assigned to receive isoflavone or placebo tablets for 6 months. Endothelium-dependent vasodilatation was measured by brachial reactivity technique along with levels of plasma soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and soluble thrombomodulin, von Willebrand factor, and tissue plasminogen activator. Differences between endothelium-dependent and endothelium-independent vasodilatation were assessed by evaluating brachial reactivity parameters after reactive hyperemia and after sublingual administration of nitroglycerin; furthermore, in the active group, the effect of isoflavones was also evaluated during the intra-arterial infusion of N-monomethyl-L-arginine. Serum levels of lipids [high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides and lipoprotein(a)] and hemostatic factors (prothrombin, fibrinogen, plasminogen activator inhibitor-1, and fibrin D-dimer) were also measured. To confirm the absorption of isoflavones, their blood concentrations were determined. RESULTS: Isoflavone treatment versus placebo was associated with a significant improvement in endothelium-dependent vasodilatation but had no impact on endothelial-independent arterial diameter and flow. Intra-arterial infusion of N-monomethyl-L-arginine inhibited the significant effect of isoflavones on endothelium-mediated vasodilatation. Furthermore, isoflavone group experienced statistically significant reductions in plasma concentrations of ICAM-1, VCAM-1, and E-selectin. Levels of soluble thrombomodulin, von Willebrand factor, tissue plasminogen activator, lipids, and hemostatic factors did not change significantly throughout the study in both groups. CONCLUSIONS: Our findings suggest a positive influence of soy isoflavones on endothelial function in healthy postmenopausal women as evidenced by an improvement in endothelium-dependent vasodilatation and a reduction in plasma adhesion molecule levels.     

Soy isoflavone supplementation and fasting serum glucose and lipid profile among postmenopausal Chinese women: a double-blind, randomized, placebo-controlled trial

OBJECTIVE: Long-term effects of soy-derived isoflavones on lipids remain uncertain, and few data are available on their effects on glycemic control. We examined the effects of isolated soy germ isoflavones on the changes in fasting glucose (FG) and lipids. DESIGN: A double-blind, randomized, placebo-controlled trial was conducted in 203 postmenopausal Chinese women aged 48 to 62 years. They were randomly assigned to receive daily doses of 500 mg calcium, and 0 mg isoflavones (placebo, n=67), 40 mg isoflavones (n=68), and 80 mg isoflavones (n=68). Serum FG, triglycerides, high-density lipoprotein, low-density lipoprotein, total cholesterol, and lipoprotein cholesterol were measured at baseline and 1 year after treatment. The primary data analysis was performed on the 203 randomized women according to the intent-to-treat principle. The last value carried forward was used for any missing data at follow-up. RESULTS: We observed moderate but significant favorable effects of soy isoflavones on the changes (P=0.012) and percentage of changes (P=0.031) in FG (analysis of variance). The 1-year mean (SD) differences of FG changes were -5.2 (-9.4 to -1.0) mg/dL (P=0.010) and -3.3 (-7.5 to 0.9) mg/dL (P=0.18) in the 40- and 80-mg isoflavone groups compared with the placebo group. We also noted a significant interaction between the treatment and baseline FG on the changes in FG (P=0.004). The isoflavone effects were much more significant in women with baseline FG 100 mg/dL or more than in those with FG less than 90 mg/dL. We observed little effect of soy isoflavones on changes in serum lipids among the treatment groups. CONCLUSIONS: One-year of soy isoflavone supplementation might have a favorable effect on FG in women, but has no significant effect on serum lipids.     

Effect on lipids, lipoproteins and apoproteins of labetalol prescribed in doses of 400 mg/day in hypertensive patients. Double-blind versus placebo study

The effects of labetalol on plasma lipoprotein metabolism were evaluated in a 3-month double-blind drug versus placebo study conducted on 30 consenting hypertensive patients, 15 of whom had normal plasma lipid levels and 15, minor type II hyperlipoproteinaemia; 20 patients received labetalol 400 mg/day and 10 the placebo. All patients remained in stable nutritional status throughout the study. Full clinical examination and blood sampling were carried out 30 days before, and on days 0, 30 and 90 of treatment. Whole blood was collected after 12 hours' fasting and immediately centrifuged prior to determination of plasma lipids (total cholesterol and triglycerides, by enzymatic assay), lipoprotein lipids (HDL, HDL2, HDL3, LDL, VLDL separated by ultracentrifugation in density gradient), apoproteins A1 and B (by laser immunonephelometry) and post-heparin lipoprotein lipase activity (PHLA). Significant changes in heart rate and systolic and diastolic blood pressures were noted in patients under labetalol but not in patients under placebo. Lipid and apolipoprotein levels were similar in both groups on day 0, and no significant variation in lipids, lipoprotein lipids and apolipoproteins were observed after 30 and 90 days of treatment with either labetalol or the placebo. At the end of treatment PHLA was unmodified in the group under placebo and raised in the group under labetalol (p = 0.05). The absence of changes in blood lipid values was found both in patients with normal lipidemia and in those with hyperlipidaemia. This study confirms that labetalol in doses of 400 mg/day has notable anti-hypertensive activity and, as previously reported and in contrast with other beta-blocking agents, is devoid of any adverse effect on lipid metabolism.     

Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial

BACKGROUND: Our aim was to assess the effects of metformin on menstrual frequency, fasting plasma glucose (FPG), insulin resistance assessed as HOMA-index, weight, waist/hip ratio, blood pressure (BP), serum lipids, and testosterone levels in women with polycystic ovary syndrome (PCOS) METHODS: In a randomized, controlled, double-blinded setup, 56 women aged 18-45 with PCOS were treated with either metformin 850 mg or placebo twice daily for 6 months. After a wash-out period of 3 months participants received the alternate treatment for 6 months. The changes in the measured parameters were analysed by intention-to-treat and per protocol. RESULTS: There were no changes in menstrual frequency. In the intention-to-treat analysis, weight and systolic BP were reduced on metformin treatment (p=0.009 and 0.047, respectively), while high-density lipoprotein (HDL) increased (p=0.001). On placebo, weight and FPG increased (p<0.05). Post-hoc subgrouping according to BMI revealed reductions in testosterone (p=0.013), FPG (p=0.018), insulin (p=0.045) and HOMA-index (p=0.022) in obese women. Per protocol analysis showed the following differences between the changes on placebo and metformin (mean (5 - 95 % percentiles): weight (-4.2 (-7.0, -1.9) kg, p<0.001), FPG (-0.23 (-0.44, -0.01) mmol/l, p=0.041), insulin (-4.17 (-8.10, -0.23) mIU/l, p=0.039) and HOMA index (-1.50 (-2.53, -0.47) mIU/l*mmol/l, p=0.006). Weight, FPG and HOMA index were lower after metformin than after placebo. CONCLUSIONS: Metformin treatment lowered weight and systolic blood pressure and increased HDL in women with PCOS. In post-hoc analysis it increased insulin sensitivity and lowered testosterone in obese women. Non-obese women did not benefit from metformin.     

ApoB/ApoA-I ratio in young patients with ischemic cerebral stroke or peripheral arterial disease

Although smoking and hypertension are classic risk factors for atherothrombotic diseases, the relationship of dyslipidemia and vascular diseases, other than myocardial infarction, is less clearly established, especially in young subjects. In the current study, a detailed analysis of the lipid and apolipoprotein profiles was conducted in young patients of ischemic cerebral stroke (IS) and peripheral arterial disease (PAD). Plasma levels of C-reactive protein (hs-CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides (TG), and apolipoproteins A-I (ApoA-I) and apolipoproteins B (ApoB), which include the ApoB/ApoA-I ratio, were analyzed in a group of 81 patients who presented with IS (n = 46) or PAD (n = 35) as well as in 167 control subjects. Significant differences were observed for hs-CRP, TC, HDLc, LDLc, TG, ApoA-I, and ApoB levels, as well as for the ApoB/ApoA-I ratio, between the control and the IS or PAD groups. However, after adjustment for sex, age, smoking, hypertension, hs-CRP, and dyslipidemia (LDLc, TC, HDLc, TG, ApoA, ApoB, and ApoB/ApoA-I ratio), hs-CRP, ApoB, and the ApoB/ApoA-I ratio were independently associated with increased risks of IS or PAD. Increased ApoB/ApoA-I ratio and hs-CRP levels are independently associated with occurrence of IS and PAD in young patients and are significant markers of alterations on lipid and apolipoproteic profiles and inflammatory responses, respectively, in these patients.     

Effect of soy isoflavone protein and soy lecithin on endothelial function in healthy postmenopausal women

OBJECTIVE: To assess the effects of soy isoflavone protein concentrate and soy lecithin on endothelial function, measured as flow-mediated dilation (FMD) of the brachial artery in healthy postmenopausal women. DESIGN: This was a randomized, double-blind, placebo-controlled crossover trial with 25 participants (mean age, 61 years; body mass index, 25.46 kg/m2). The women underwent endothelial function testing at baseline and after 4 weeks of randomly assigned treatment with intervening 4-week washout periods. Treatment assignments included soy isoflavone protein (25 g/day) and soy lecithin (20 g/day), soy isoflavone protein (25 g/day) and placebo lecithin, placebo protein and soy lecithin (20 g/day), and double placebo. FMD and serum lipid levels were assessed at baseline and the end of each 4-week treatment phase. RESULTS: Twenty-two women completed the trial. No statistically significant (P > 0.05) difference was seen in FMD between treatment groups. A trend was suggested with FMD highest after treatment with soy protein plus lecithin (7.50 +/- 9.85), followed by soy protein (5.51 +/- 10.11), soy lecithin (5.35 +/- 6.13), and lowest after placebo (4.53 +/- 7.84). Soy isoflavone protein and soy lecithin significantly increased the high-density lipoprotein/low-density lipoprotein ratio (soy isoflavone protein plus soy lecithin, 0.64 +/- 0.19, P < 0.0001; soy isoflavone protein plus placebo lecithin, 0.58 +/- 0.17, P = 0.0058; placebo protein plus soy lecithin, 0.65 +/- 0.18, P < 0.0001) relative to the baseline value (0.49 +/- 0.15). CONCLUSIONS: In this sample of healthy postmenopausal women, soy isoflavone protein and soy lecithin significantly improved the lipid profile. A favorable influence on endothelial function could not be confirmed.     

Theophylline does not inhibit allergen-induced increase in airway responsiveness to methacholine

Allergen-induced increase in airway hyperresponsiveness can be used as a model of airway inflammation for assessing antiasthma pharmacologic agents. Steroids and cromolyn, but not beta-agonists, inhibit this increase; theophylline, recently suggested as having anti-inflammatory effects, has not been evaluated in this model. Six atopic subjects with asthma and with late asthmatic responses (N = 5) and postallergen reduction in a provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) (N = 6) were studied. Sustained-release theophylline (Theo-Dur; Astra Pharmaceuticals Canada, Ltd., Mississauga, Canada), 300 mg, and placebo were administered single-blind twice daily for eight doses up to 1 hour before allergen inhalation; cromolyn sodium, 10 mg, was administered in a single dose 10 minutes before allergen inhalation on another day as a "positive control." Mean theophylline levels were in the low therapeutic range, 57 +/- 17 and 58 +/- 13 mumol/L 1 and 8 hours after the last tablet. The FEV1 was 7% and 9% greater after the seventh and eighth doses of theophylline versus placebo (p less than 0.05). Theophylline also produced a significant (p less than 0.05) twofold increase in methacholine PC20. There was a 40% (p = 0.06) reduction in early asthmatic fall in FEV1 and a 25% (not significant) reduction in late FEV1 fall when theophylline was compared to placebo. Theophylline did not influence the geometric mean allergen-induced fall in methacholine PC20 delta log PC20; this was true individually in five of the six subjects. By contrast, cromolyn sodium inhibited all aspects of the allergen response completely.(ABSTRACT TRUNCATED AT 250 WORDS)