Development of an UHPLC-diode arrays detector (DAD) method for the analysis of polydatin in human plasma.

A new chromatographic method by Ultra High Performance Liquid Chromatographic (UHPLC) technology, has been developed and validated for the determination of polydatin and resveratrol, as potential metabolite, in human plasma. After the optimization of the chromatographic conditions, the method has been validated on spiked human plasma samples. The optimized extraction allowed to obtain analytes recovery up to 98.48 ± 4.03 %. Then, the isocratic elution in reversed phase mode, provides the separation of polydatin and resveratrol in less than 10.0 min. Chromatographic analysis was performed on a C18, 10 cm x 3.0 mm, 2.7 µm stationary phase, by using triethanolamine phosphate solution (0.1 M, pH = 3.7) and ACN 85:15 (v/v) as mobile phase at a flow rate of 0.5 mL/min. The UV detector was set at 306 nm for the analysis of both polydatin and resveratrol. The limit of detection (LoD) and the limit of quantification (LoQ) for polydatin in plasma samples were found to be 7.82 ± 0.38 nM and 26.06 ± 1.28 nM respectively. The method was found to be accurate and precise with a coefficient for intra- and inter-day variation below 5 %. All the reported data demonstrate how the developed method is rapid and sensitive. Moreover, results of the analysis of plasma samples, obtained from orally treated volunteers with nutritional supplements containing polydatin, have shown the method to be suitable for the pharmacokinetic characterization of polydatin and resveratrol, as metabolite, in humans.

Creatine Phosphate Administration in Cell Energy Impairment Conditions: A Summary of Past and Present Research.

BACKGROUND: Creatine phosphate (CrP) plays a fundamental physiological role by providing chemical energy for cell viability and activity, especially in muscle tissue. Numerous pathological conditions, caused by acute or chronic ischaemic situations, are related to its deficiency. For these reasons, it has been used as a cardioprotective agent in heart surgery and medical cardiology for many years. OBJECTIVE: This article gives a brief overview of the main characteristics of exogenous CrP. METHODS: Previous review articles on CrP were screened for relevant information and references. Results from selected studies were reviewed and classified according to the topics in this review article and provided further interesting information on the pharmacological role of this molecule. RESULTS: Besides CrP's well known cell energy and function restoring properties, new evidence is emerging regarding its antioxidant and anti-apoptotic properties. Use of CrP is well established clinically as an intraoperative and perioperative adjuvant in heart operations (valve replacement, coronary artery bypass grafting, congenital heart defect repair), and as an additional agent in medical cardiology therapy for acute myocardial infarction and acute and chronic heart failure. In particular, there are promising potential new CrP uses in neurology, such as in cerebral ischaemia and hypoxic ischaemic encephalopathy. CONCLUSIONS: This review article describes the role of CrP treatment in cardiological indications, such as cardioprotection in cardioplegia and in myocardiopathies of various etiopathogenesis, as well as in other clinical indications such as skeletal muscle rehabilitation and neurological conditions.

Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens.

OBJECTIVES: To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. STUDY DESIGN: This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). METHODS: Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and switching therapy. A timespan of 5 years was considered, from 4 years before to 1 year after the index date (i.e. date of the prescription selected in the recruitment period). A medication possession ratio (MPR) with a cut-off value of 80% was used to measure medication adherence. Descriptive statistics and multiple logistic regression were used to define the objectives, while P < 0.05 was considered to indicate significance. RESULTS: The median age of patients (n = 169,375, prevalence 4.2%) was 70 years [interquartile range (IQR) 17], and 49.1% were females. Considering the entire sample, the median MPRs for the treatment regimens were: MT, 0.73 (IQR 0.53; 43.9% compliant); FDCT, 1 (IQR 0.29, 68,5% compliant); and LDCT, 0.89 (IQR 0.33, 60.3% compliant). FDCT and LDCT were significantly correlated with MPR. Compliance was 48.9% in the prevalent patient cohort (i.e. patients prescribed oral antidiabetic therapy in both prerecruitment and recruitment periods); median MPRs for the treatment regimens were: MT, 0.73 (IQR 0.52); FDCT, 1 (IQR 0.28); and LDCT, 0.90 (IQR 0.32). Compliance was 43.0% in the incident patient cohort (i.e. patients who were first prescribed oral antidiabetic therapy in the recruitment period); median MPRs for the treatment regimens were: MT, 0.70 (IQR, 0.58); FDCT, 1 (IQR 0.34); and LDCT, 0.64 (IQR 0.39). CONCLUSIONS: Compliance was better for FDCT than the other therapeutic regimens in the study population. The same trend was observed in both the prevalent and incident patient cohorts. As type 2 diabetes is a chronic lifelong pathology, and multiple agents are often required to achieve glycaemic control, the preference for FDCT in the population, when clinically applicable, could be an effective strategy for functional administration of clinical outcome and sources. Evaluation of specific population fractions (age, sex, compliance, etc.) and specific agents or drug combinations could also be relevant in order to reach the healthcare objectives.

Otoscopic findings in hypercholesterolemic subjects.

OBJECTIVES: We aimed to verify the extent of a previously cited relationship between tympanosclerosis and atherosclerosis by investigating subjects with dysfunction in lipid metabolism but no clinically apparent symptoms of atherosclerotic disease. METHODOLOGY: Forty hypercholesterolemic patients were submitted to Doppler ultrasound examination of carotid and vertebrobasilar arterial regions; results were matched to otoscopic findings. Otoscopy was performed to evaluate for sclerotic plaques of the tympanic membrane, which represent the most common, clinically non-relevant manifestation of tympanosclerosis. A control group of 41 randomly chosen healthy subjects were also included. RESULTS: Nine (22.5%) of 40 subjects with hypercholesterolemia showed tympanic sclerotic plaques at otoscopy compared to 2 (4.9%) out of 41 control patients. This difference was statistically significant (p = 0.02). An even stronger association (p = 0.01) was found between tympanic and arterial plaques in the study group, as we identified tympanic sclerotic plaques in 7 (41.2%) out of 17 patients with positive Doppler ultrasound signals for arterial plaques. Only two (8.7%) out of 23 subjects without plaques on Doppler ultrasound examination had tympanic sclerotic plaques. CONCLUSIONS: The results of this study confirm the existence of a link between tympanosclerosis and atherosclerosis. To our knowledge, this is the first report of a link between these findings in preclinical atherosclerotic conditions.

Effect of sulodexide on albuminuria, NAG excretion and glomerular filtration response to dopamine in diabetic patients.

BACKGROUND: Albuminuria is the best and most readily available marker for glomerular damage and progressive renal function loss in patients with diabetic nephropathy. Recently, administration of the oral glycosaminoglycan sulodexide (a mixture of 80% fast-moving heparin and 20% dermatan sulphate) was shown to effectively decrease albumin excretion rate in diabetics with nephropathy. AIMS: To evaluate whether the hypoalbuminuric effect of sulodexide is associated with improvement of the renal vascular or tubule function. METHODS: Forty-five type 1 diabetic patients, affected by diabetic nephropathy with albuminuria for at least 5 years, were randomly allocated to sulodexide or untreated. Those allocated to sulodexide were given 100 mg of sulodexide daily for 120 days. Renal vascular function (DIR) and N-acetyl-beta-D-glucosaminidase (NAG) excretion were estimated before and at the end of the study, the former in thesulodexide group only. DIR was measured as two Cr(cl) lasting 120 min (before and during 2 mug/kg b.w. i.v. dopamine). RESULTS: The analysis of trends during the study demonstrated a marked reduction of albuminuria in the sulodexide group (from 126.1 +/- 15.41 to 93.6 +/- 13.7 mg/day). DIR rose from 13.2 +/- 2.1% to 15.44 +/- 1.9% (relative increase: +16.9%), and NAG excretion showed a decreasing trend decreased in the sulodexide group only (from 5.1 +/- 0.62 to 4.7 +/- 0.40 U/g(creat)). CONCLUSION: The findings presented in this study indicate for the first time that orally available sulodexide may favorably affect the renal vascular function in type 1 diabetic patients with nephropathy and microalbuminuria. The effect of sulodexide on NAG is strongly influenced by the baseline NAG values, with a significant NAG reduction in the patients with the highest baseline NAG values.

Differential effect of glimepiride and rosiglitazone on metabolic control of type 2 diabetic patients treated with metformin: a randomized, double-blind, clinical trial.

AIM: Accumulating evidence suggests that combination therapy using oral antidiabetic agents with different mechanisms of action may be highly effective in achieving and maintaining target blood glucose levels. The aim of our study is to evaluate the differential effect on glucose and lipid parameters of the association between glimepiride plus metformin and rosiglitazone plus metformin in patients affected by type 2 diabetes and metabolic syndrome. METHODS: Patients were enroled, evaluated and followed at two Italian centres. We evaluated 99 type 2 diabetic patients with metabolic syndrome (48 males and 47 females; 23 males and 24 females, aged 52 +/- 5 with glimepiride; 25 males and 23 females, aged 54 +/- 4 with cglitazone). All were required to have been diagnosed as being diabetic for at least 6 months and did not have glycaemic control with diet and oral hypoglycaemic agents such as sulphonylureas or metformin, both to the maximum tolerated dose. All patients took a fixed dose of metformin, 1500 mg/day. We administered glimepiride (2 mg/day) or rosiglitazone (4 mg/day) in a randomized, controlled, double-blind clinical study. We evaluated body mass index (BMI), glycaemic control, lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and triglycerides] and lipoprotein parameters [apolipoprotein A-I and apolipoprotein B (Apo B)] during 12 months of this treatment. RESULTS: A total of 95 patients completed the study. Significant BMI decrease was observed at 12 months in glimepiride and rosiglitazone group (p < 0.05 and p < 0.01 respectively) as well as of glycated haemoglobin decrease (p < 0.05 and p < 0.01 respectively), mean fasting plasma glucose and postprandial plasma glucose levels (p < 0.05 and p < 0.01 respectively). A decrease in fasting plasma insulin and postprandial plasma insulin at 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group was observed. Furthermore, homeostasis model assessment index improvement was obtained only at 9 and 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group. Significant TC, LDL-C and Apo B improvement (p < 0.05 respectively) was present in glimepiride group after 12 months compared with the baseline values, and these variations were significant (p < 0.05) between groups. Of the 95 patients who completed the study, 8.5% of patients in glimepiride group and 12.5% of patients in rosiglitazone group had side-effects (p = not significant). Four patients had transient side-effects in glimepiride group and six patients in rosiglitazone group. Altogether, we did not have statistically significant changes in transaminases. CONCLUSIONS: The rosiglitazone-metformin association significantly improve the long-term control of all insulin-resistance-related parameters in comparison with the glimepiride-metformin-treated group. On the other side, glimepiride treatment is associated to a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients.

[Treatment of peripheral obstructive artery disease: a battle that could be winned also with drugs?]. / Trattamento dell'arteriopatia obliterante degli arti inferiori: una battaglia che può essere vinta anche con i farmaci?

The peripheral obstructive artery disease (POAD) epidemiology raises some concerns about its continuously increased incidence in Western countries. The most part of the patients affected by POAD have systemic cardiovascular complications and die because of cardiac and cerebrovascular disorders. Thus the social cost of this disease is very high. A large part of risk factors for the POAD is well-known and they are reversible trough an efficacious life-style improvement (mainly physical activity increase and cigarette smoking habit cessation) and cardiovascular disease risk factors control (diabetes mellitus, hypercholesterolemia, blood hypertension). On the contrary, no much data are available as it regards efficacious therapies for clinically active disease. The only ones that have been adequately investigated and already available in the market are cilostazol (maybe useful only in more serious patients), and sulodexide (that could improve the pain free walking distance till the 75%). Further research is needed in order to develop new efficacious drugs for POAD treatment, but in the meantime it is necessary to recognise all POAD patients as soon as possible and to treat them adequately with the available therapies.

REVERSAL and PROVE-IT: are clinically oriented trials really better than "pure" scientific studies?

Recently, two large randomised clinical trials compared the effects of standard and intensive lipid-lowering treatment (Pravastatin 40 mg vs. Atorvastatin 40 mg b.i.d.) on patient prognosis after acute coronary syndromes--the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT), and on the atherosclerosis regression--the Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL). Undoubtedly, the event-rate reduction and the atherosclerosis regression associated to intensive hypocholesterolemic treatment in these studies are impressive, however we would like to highlight some methodological concerns raised by both trials, more clinically oriented than planned to give rigorous answers to the scientist. The main problems of both studies are that they compare the effects of statins with different pleiotropic and pharmacokinetic properties and that the metabolic disorders that affect the studied patients have not been clearly described. Moreover, it is unclear if the cardiovascular disease history length was similar in the two treatment groups as well as the length and dosage of statin treatment of the about 25% of patients taking statins before the enrollment. Waiting for studies comparing the effects of low and high dosages of the same statin or the high dosage of two similarly potent and rapid lipid-lowering effect (as for instance atorvastatin and rosuvastatin), prudence has to be applied in the interpretation (and even more in the application) of these large and expensive study results, that have yet only confirmed the relevance of a more intensive lipid-lowering treatment in all patients affected by atherosclerosis-based coronary syndromes.

Relative role of major risk factors for Type 2 diabetes development in the historical cohort of the Brisighella Heart Study: an 8-year follow-up.

AIM: The aim of this study was to evaluate and quantify the role of different risk factors in the long-term development of Type 2 diabetes mellitus in a rural Italian population. METHODS: The Brisighella Heart Study (BHS; 1972-2003) is a prospective, population-based longitudinal epidemiological cohort involving 2939 randomly selected subjects, aged 14-84 years, resident in the rural Italian town of Brisighella. For this study, we randomly selected 1441 adult subjects representative of the Brisighella population; consecutively visited during three BHS surveys. A step-wise Cox regression analysis determined the prognostic significance of each independent risk factor for the development of Type 2 diabetes in the 8-year long follow-up. RESULTS: Blood pressure, high-density lipoprotein cholesterol, triglycerides, physical activity, total energy intake, and drug treatment had no effect on the incidence of diabetes. Age was a significant predictor of Type 2 diabetes when inserted alone in the model (P = 0.007), but irrelevant when adjusted for baseline body mass index (BMI) and or fasting plasma glucose. Among these with impaired fasting glucose (IFG), the diabetes incidence/year was estimated to be 6.6% for men and 11.2% for women (P < 0.001). Basal glycaemia under 6.1 mmol/l were not significant long-term predictors of diabetes development, while higher basal glycaemia and each level BMI were. CONCLUSION: Our findings confirm that IFG and BMI predict Type 2 diabetes development in our population. This should help to identify effective approaches to prevention.

Possible role of ubiquinone in the treatment of massive hypertriglyceridemia resistant to PUFA and fibrates.

OBJECTIVE: To describe the effect of Coenzyme Q10 (CoQ10) (added to either a fibrate, or polyunsaturated fatty acids (PUFA) or association of both) in patients affected by massive hypertriglyceridemia (MHTG) resistant to fibrates and PUFA. DESIGN: Open, sequential, comparative intervention study. SETTING: Specialised centres for dyslipidemia management. SUBJECTS: Fifteen subjects (mean age: 45.1+/-12.5 years) affected by MHTG and hyporesponsive to either fibrates, or PUFA, or fibrates-PUFA association, and 15 age-matched subjects regularly responders to PUFA and fenofibrate treatment. INTERVENTIONS: Treatment for periods of 6 weeks each with the following consecutive treatments: CoQ10 150 mg/day, PUFA 3000 mg/day, fenofibrate 200 mg/day, PUFA 3000 mg/day+fenofibrate 200 mg/day, PUFA 3000 mg/day+CoQ10 150 mg/day, fenofibrate 200 mg/day+CoQ10 150 mg/day, and finally, fenofibrate 200 mg/day+PUFA 3000 mg/day + CoQ10 150 mg/day. RESULTS: CoQ10 supplementation did not improve any monitored parameter in the control group except for systolic and diastolic blood pressure, creatinine and Lp(a) plasma levels, both during fenofibrate and/or PUFA treatment. In MHTG group, CoQ10 supplementation significantly improved TG, TC, Lp(a), uric acid and blood pressure during fenofibrate treatment, but only Lp(a) and blood pressure during PUFA treatment. Fenofibrate appeared to have better effect on hsCRP and gamma-GT plasma levels than PUFA. No significant change was observed in any group and under any treatment in regards to homocysteinemia, PAI-1, or t-PA. CONCLUSION: Even though the mechanism of action through which the effects were obtained is yet to be elucidated, adding CoQ10 to fenofibrate could improve the drug's efficacy in MHTG patients not responding to fenofibrate alone.

Long-term effect of glimepiride and rosiglitazone on non-conventional cardiovascular risk factors in metformin-treated patients affected by metabolic syndrome: a randomized, double-blind clinical trial.

We evaluated the effect of glimepiride plus metformin and rosiglitazone plus metformin on glucose, and on cardiovascular risk parameters such as lipoprotein(a) (Lp[a]) and homocysteine (HCT) in patients with type 2 diabetes and metabolic syndrome. Ninety-nine patients in the multicentre, randomized, double-blind study took metformin (1500 mg/day) plus glimepiride (2 mg/day) or rosiglitazone (4 mg/day) for 12 months. Changes in body mass index, glycosylated haemoglobin (HbA1c), Lp(a) and HCT were primary efficacy variables. Fasting plasma glucose (FPG), post-prandial plasma glucose (PPG) and homeostasis model assessment index were also used to assess efficacy. On average, HbA1c decreased by 9.1% and 8.1%, FPG decreased by 7.3% and 10.9%, and PPG decreased by 7.6% and 10.5%, respectively, in the glimepiride and rosiglitazone groups after 12 months. Patients receiving rosiglitazone experienced more rapid improvement in glycaemic control than those on glimepiride, and showed a significant improvement in insulin resistance-related parameters. There was a statistically significant decrease in basal homocysteinaemia in glimepiride-treated patients (-27.3%), but not in rosiglitazone-treated patients. Rosiglitazone plus metformin significantly improved long-term control of insulin resistance-related parameters compared with glimepiride plus metformin, although glimepiride treatment was associated with a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients, and with significant improvements in non-traditional risk factors for cardiovascular disease, such as basal homocysteinaemia and plasma Lp(a) levels.

Treatment of massive hypertriglyceridemia resistant to PUFA and fibrates: a possible role for the coenzyme Q10?

OBJECTIVE: To describe the effect of CoQ10 (added to either a fibrate, or PUFA or association of both) in patients affected by massive hypertriglyceridemia (MHTG) resistant to fibrates and PUFA. DESIGN: Open, sequential, comparative intervention study. SETTING: Specialised centres for dyslipidemia management. SUBJECTS: 15 subjects (mean age: 45.1 +/- 12.5 years) affected by MHTG and hyporesponsive to either fibrates, or PUFA, or fibrates-PUFA association, and 15 age-matched subjects regularly responders to PUFA and fenofibrate treatment. INTERVENTIONS: Treatment for periods of 6 weeks each with the following consecutive treatments: CoQ10 150 mg/day, PUFA 3000 mg/day, fenofibrate 200 mg/day, PUFA 3000 mg/day + fenofibrate 200 mg/day, PUFA 3000 mg/day + CoQ10 150 mg/day, fenofibrate 200 mg/day + CoQ10 150 mg/day, and finally, fenofibrate 200 mg/day + PUFA 3000 mg/day + CoQ10 150 mg/day. RESULTS: CoQ10 supplementation improved, in the control group, systolic and diastolic blood pressure, creatinine and Lp(a) plasma levels, both during fenofibrate and/or PUFA treatment. In MHTG group, CoQ10 supplementation significantly improved TG, TC, Lp(a), uric acid and blood pressure during fenofibrate treatment, but only Lp(a) and blood pressure during PUFA treatment. Fenofibrate appeared to have better effect on hsCRP and gamma-GT plasma levels than PUFA. No significant change was observed in any group and under any treatment in regards to homocysteinemia, PAI-1, or t-PA. CONCLUSION: Even though the mechanism of action through which the effects were obtained is yet to be elucidated, adding CoQ10 to fenofibrate could improve the drug's efficacy in MHTG patients not responding to fenofibrate alone.

Effects of Siberian ginseng (Eleutherococcus senticosus maxim.) on elderly quality of life: a randomized clinical trial.

An unspecific feeling of fatigue and asthenia often pushes elderly patients to require any form of help even from non medically trained people. Traditional Chinese medicine suggest that Siberian ginseng could act as safe "adaptogenic" substance. Our aim was thus to test the effect of a middle term Eleutherococcus senticosus Maxim. (Araliaceae) administration on elderly, health related quality of life (HRQOL). 20 elderly hypertensive and digitalized volunteers (age >/= 65 years) were randomized in a double -blind manner to E. senticosus dry extract 300 mg/day (n = 10) or placebo (n = 10) for 8 weeks. The short form-36 health survey version 2 (SF-36v2), a validated general health status questionnaire, was used to access HRQOL at baseline and at 4 and 8 weeks. There were no significant differences in baseline demographics and SF-36v2 scores between the groups. At each visit, controls of digitalemia and blood pressure level were carried out. After 4 weeks of therapy, higher scores in social functioning (p = 0.02) scales were observed in patients randomized to E. senticosus; these differences did not persist to the 8-week time point. No adverse event has been observed in both groups of patients. No significant difference in both blood pressure control and digitalemia was observed in both treatment groups. Subjects give E. senticosus (70%) were more likely to state that they received active therapy than subjects given placebo (20%; p < 0.05). In conclusion, E. senticosus safely improves some aspects of mental health and social functioning after 4 weeks of therapy, although these differences attenuate with continued use.

Assessment of the health status in the Massa Lombarda cohort: a preliminary description of the program evaluating cardio-cerebro-vascular disease risk factors and quality of life in an elderly population.

The Massa Lombarda program (MLP) is the first step of a European multi-center program, promoted and coordinated from Bologna University's Academic Spin off Health Research and Development, which attempts to manage advanced sanitary research in general population. The instant individual definition (IID) study is the first phase of the program concerning the study of risk factors (RF) and early diagnosis of coronary heart disease (CHD), through a new diagnostic technology called myocardial perfusion scoring system (MPS). The study consists of a longitudinal observational epidemiological investigation of adult population (above 25 years of age) resident in Massa Lombarda (Ravenna), with the survey of social and biological parameters. The elderly part of the population (1000 subjects above 75 years) was submitted to a more complex analysis, as part of the study on health status in European aging populations, aimed at revealing the determinants influencing the healthy aging, and at identifying their impact on mortality,cardiovascular and respiratory morbidity, disability and decline of quality of life. Laboratory analyses were aimed at identifying the following factors: (i) Genetic markers related to pro and anti-inflammatory cytokine- codifying genes. (ii) Oxidative stress-involved molecules,and inflammation-involved genes, and more in general genes involved in the brittleness(iii) (ApoE). Appraising the degree of interaction with non-genetic factors, like measurable immunological markers in the peripheral blood, markers of reactions to oxidative stress,evaluation of metabolic parameters. Moreover, old population is expected to answer the questionnaires for evaluation of the dietary habits, physical activity, self-sufficiency,cognitive ability, motor coordination, perceived stress and social relationships.

What do herbalists suggest to diabetic patients in order to improve glycemic control? Evaluation of scientific evidence and potential risks.

In the course of 12 continuing education seminars given in different regions of Italy in 2001, we distributed a questionnaire to all the attending herbalists asking information about the herbal remedy and dietary supplement they mainly recommended to subjects who required a "natural" treatment to control glycemia. We distributed 720 questionnaires and we received 685 completed ones. We have compiled a short review on the efficacy and safety of the 10 most frequently advised products for each category. The 10 more frequently suggested herbal remedies were gymnema, psyllium, fenugreek, bilberry, garlic, Chinese ginseng, dandelion, burdock, prickly pear cactus, and bitter melon. The 10 most frequently recommended dietary supplements were biotin, vanadium, chromium, vitamin B6, vitamin C, vitamin E, zinc, selenium, alpha-lipoic acid, and fructooligosaccharides. The majority of the products recommended by Italian herbalists may be efficacious in reducing glycemia. If a diabetic patient is already assuming products that even slightly reduce glycemia, we risk to underestimate the level of glucose intolerance, while if the patient stops the complementary treatment after initiating pharmaceutical therapy, in the subsequent visit we may underestimate the effect of our prescription. Therefore, if doctors are to have a role in gate-keeping or advising patients about complementary and alternative medicine, they need to be familiar with this type of medicine. If they choose otherwise, then the provision of complementary and alternative medicine will continue to be patchy and largely outside the conventional care framework, perhaps through a growing network of parallel care providers involving a large number of non-medically qualified practitioners, who patients will continue to access directly.

Rice bran oil and gamma-oryzanol in the treatment of hyperlipoproteinaemias and other conditions.

Diet is the first (and sometimes the only) therapeutic approach to hyperlipoproteinaemias. Rice bran oil and its main components (unsaturated fatty acids, triterpene alcohols, phytosterols, tocotrienols, alpha-tocopherol) have demonstrated an ability to improve the plasma lipid pattern of rodents, rabbits, non-human primates and humans, reducing total plasma cholesterol and triglyceride concentration and increasing the high density lipoprotein cholesterol level. Other potential properties of rice bran oil and gamma-oryzanol, studied both in vitro and in animal models, include modulation of pituitary secretion, inhibition of gastric acid secretion, antioxidant action and inhibition of platelet aggregation. This paper reviews the available data on the pharmacology and toxicology of rice bran oil and its main components with particular attention to those studies relating to plasma lipid altering effects.

The realization of a project aimed at reducing the plasmatic lipid level in a large Italian population improves the mean calcium daily intake: the Brisighella Study.

OBJECTIVES: Evaluation of the impact of a coronary heart disease prevention program on calcium, magnesium, phosphorus and vitamin D dietary intake in respect of recommended daily allowances in a large Italian rural population. DESIGN: Retrospective analysis of the Brisighella Study dietary data. The Brisighella Study started in 1972 as a longitudinal study on atherosclerosis risk factors. SETTING: Brisighella, a rural North Italian village. SUBJECTS: The Brisighella population's dietary habits were monitored from 1980 every 4 h through a dietary record sheet. 1,350 constantly tested subjects were subdivided according to NHI Consensus Conference on Calcium RDA. INTERVENTION: In 1986, the studied subjects were invited to reduce their consumption of animal fats and cholesterol through a Nutrition Educational Program (NEP). RESULTS: Before NEP, calcium intake was low in each sex and age category: 20-40% of the populatioin had a daily intake < 550 mg. In 1988, among the 1350 subjects who constantly completed the questionnaire (M = 651, F = 699), the mean calcium intake significantly rose in all age categories: M = 1,003 (25-65 y) and 877 ( > 65) mg/24h (P < 0.001 vs 1984); F = 923 (25-50), 860 (51-65) and 767 (> 65)mg/24h (P < 0.05). In 1992, 3y after the NEP conclusion, calcium intake dropped in each sex and age category. The NEP influenced vitamin D, phosphorus and magnesium intakes less. CONCLUSIONS: A collective NEP aimed at lowering saturated fats and cholesterol intakes, improves the calcium intake; in order to maintain their efficacy on nutritional habit changes, these programs must become an ongoing item.

The effect of insulin and sulodexide (Vessel Due F) on diabetic foot syndrome: pilot study in elderly patients.

OBJECTIVE: To assess the efficacy of insulin plus sulodexide (a mixture of 80% heparin-like substances and 20% dermatan sulphate) on diabetic ulcers, and its influence on foot skin microcirculation and diabetic neuropathy. RESEARCH DESIGN AND METHODS: Two groups of diabetic patients, suffering from severe neuropathy and ulceration, were randomly assigned to insulin (I) plus sulodexide (S) (n=12) or insulin plus placebo (P) (n=6) therapy, for 10 weeks. Laser Doppler assessment of foot skin flow (LDF), at rest and 30 or 60 s after arterial occlusion, and nerve conduction tests (sensorial evoked and motoric conduction potentials) have been evaluated in both groups. RESULTS: Postischaemic flow was 2.5 times shorter in ulcerated vs. non-ulcerated feet in diabetic patients. A significant increase in flows after 30 and 60 s ischaemia was detected in both groups at the end of therapy (IS group, ulcerated foot, LDF=60 s: from 99.1+/-14.3 to 218.6+/-28.6 PU, P<.001. IP group=from 110.5+/-13.0 to 164.8+/-15.4 PU, P<.05). The length of reactive hyperaemia was higher in IS vs. IP group (IS: from 30.3+/-2.9 to 43.9+/-2.2 s, P<.001; IP: from 28.7+/-3.0 to 33.3+/-3.3 s, ns). Ninety-two percent of ulcers heals in a mean time of 46.4 days (IS group) vs. 83% and 63.0 days, respectively, in IP group. Nerve conduction studies have not demonstrated within- and between-group differences. CONCLUSIONS: Sulodexide and insulin improve the postischaemic skin flow in ulcerated feet, without affecting nerve conduction tests. The effect of sulodexide results additive to insulin; it is clinically relevant, in the view of the possibility of reducing the time needed to completely heal ulcers. The ultimate validation of these preliminary results requires extensive trials.

A suggestion for familial hypercholesterolemia (FH) heterozygosity clinical diagnosis based on epidemiological observations in a large Italian population.

We selected 247 subjects from 29 large familial hypercholesterolemia (FH) kindreds from 550 probable FH subjects in Emilia Romagna (Italy) on the basis of LDL-cholesterol plasmatic levels and family trees, in order to define the best diagnostic criteria for heterozygous patients. Familial hypercholesterolemia is a monogenic disease of cholesterol metabolism inherited as an autosomal dominant trait and characterised by early cardiovascular disease. A low xanthomas and xanthelasmas prevalence was found (8.6%); coronary heart disease (CHD) death occurs very frequently in heterozygous males (72% of all deaths; mean age at death 52 years), while in females the primary cause of death was thrombotic stroke (55%; mean age 69 years). Total cholesterol (TC) mean values were 389.8 (m) and 373.3 mg/dl (f) for FH trait carriers, and 223.3 (m) and 228.8 (f) for healthy relatives. No age-related change in TC was found in heterozygotes, while unaffected relatives of FH families showed mean TC and LDL-C values, and a TC frequency distribution and a TC age-related increasing trend similar to the expected values for the Italian population. The TC frequency distribution curve appeared bimodal, with a mid-point between heterozygous and homozygous FH modal values of 280 mg/dl. To identify the FH patients, the final FH heterozygosity risk was evaluated in an unselected free-living population (from 0.07 to 0.8%, respectively, for TC between 265-274 and 295-304 mg/dl) and in hypercholesterolemic families (31 to 83%, and the same TC classes). Our conclusion is that the clinical picture is rarely pathognomonic, while the FH heterozygosity final risk evaluation and the 280 mg/dl cut-off point can be used to guide the practical clinical diagnosis and to select the patients destined for B-E receptor activity evaluation.