[Lifestyle and global cardiovascular risk: a prospective study on a borderline hypertensive population]. / Stile di vita e rischio cardiovascolare globale: studio osservazionale su una popolazione di pazienti con ipertensione arteriosa borderline.

BACKGROUND AND AIMS: Arterial hypertension is a well known risk factor for cardiovascular diseases. Today, it is possible to calculate the cardiovascular risk at 10 years with the risk card. The reduction of cardiovascular risk is based on a multi-factorial approach including the lifestyle modification. In Italy, OEC study has calculated that a certain proportion of borderline hypertensives, not eligible for a pharmacological treatment, remain at risk. Borderline arterial hypertension (140-150/90-95 mmHg) in Italian population is documented in 19% of males and 14% of females.: Aim of the study is to examine the efficacy of the lifestyle changes in reducing the global cardiovascular risk in bordeline hypertensives. MATERIALS AND METHODS: 102 patients affected by borderline hypertensive (46 M and 56 F, mean age: 55.6 yrs ) were enclosed in a 12 months prospective study. Three checks were programmed during the follow-up, i.e., at beginning, 6 months and 12 months later. At the start of the study every patient received a list of lifestyle changes to be respected. Pressure arterial systolic and diastolic were obtained at beginning and at the end of successive. At the last check each patient received a questionnaire to be filled up. According to the calculated score, each patient was classified as: non-responder (score: 0-3), partially responder (score: 4-6), responder (score: 7-9). RESULTS: A significant reduction of the globalcardiovascular risk has been observed at the end of the study in both the responders and partially responders. Such a reduction was seen to be due to positive changes in blood pressure and total, HDL, LDL cholesterol. CONCLUSIONS: This study confirmed that a non-pharmacological therapy based on lifestyle changes has to be preventively administered in the presence of a borderline hypertension because of its beneficial effects in reducing the global risk of cardiovascular disease. Therefore, we firmly think that a prompt utilization of a correct lifestyle can sort the triple effect of improving the expectancy of life, ameliorating the quality of life, reducing the social costs of arterial hypertension.

[Efficacy-safety relationship of AT1 angiotensin II receptor antagonists: current data]. / Rapporto efficacia-sicurezza degli antagonisti recettoriali AT1 per l'angiotensina II: dati attuali.

In evolution of hypertension's treatment it may no be sufficient to lower blood pressure to achieve beneficial effects in long term outcomes. Several goals of antihypertensive treatment remain unrealized. There is so great interest for new drugs that may protect target organs and improve outcomes. The angiotensin II, the major effector of the renin-angiotensin-aldosterone system, causes a variety of potentially noxious cardiovascular effects which are specially mediated by AT1 subtype receptors. AT1 receptor blockers (losartan, candesartan, irbesartan, valsartan) are available drugs in the angiotensin-II-antagonist class. This paper examine the peculiar features of this new class of drugs.

[Rationale for the use of renin-angiotensin inhibitors in the treatment of arterial hypertension and correlated organ damage]. / Razionale per l'uso degli inibitori del sistema renina-angiotensina nella terapia dell'ipertensione arteriosa e del danno d'organo correlato.

The treatment of hypertension has evolved in recent years. Blood pressure lowering per se is no longer a sufficient parameter to evaluate its beneficial effects on end-organ damage. Drugs must be considered on the basis of their effects on cellular level and structural alterations that occur in the vasculature, heart and kidney. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, two classes of drugs that inhibit angiotensin II effects, may protect target organs from damage and thereby improve outcomes. The mechanisms of action are different even if both counteract all noxious effects of angiotensin II. Angiotensin II receptor blockers selectively inhibit AT1 receptors whose stimulation mediates the hypertensive and proliferative effects of angiotensin II while do not interfere with AT2 receptors. These last ones have a role not well established but it has been postulated that they have antihypertensive and antiproliferative effects. A review will be made on the cellular mechanisms of angiotensin II activity and the effects of AT receptor antagonists.

Skin diseases as extrahepatic manifestations of HCV. Review of some clinical cases.

Among extra-hepatic manifestations of hepatitis C virus (HCV) infection particular interest is focused on some dermatological diseases such as: leukocytoclastic vasculitis, oral lichen planus, pruritus-urticaria, psoriasis. Aim of this paper is to analyze these typical dermatoses in a population of patients with HCV infection and describe the characteristic clinical pictures. These clinical pictures confirm the importance of liver examination in presence of skin diseases not related to other pathogenetic mechanisms.

Purity evaluation of 6 alpha-methylprednisolone acetate by HPLC.

A high-performance liquid chromatographic method is described for the analysis and identification of related impurities in pharmaceutical-grade 6 alpha-methylprednisolone acetate (MPA). Eight MPA impurities derived from synthesis and/or degradation processes were identified. The method is compared to other analytical procedures recently proposed for the European Pharmacopoeia.

The identification of related substances in triamcinolone acetonide by means of high-performance liquid chromatography with diode array detector and mass spectrometry.

A study of an HPLC method for the analysis of related substances in triamcinolone acetonide is described. Several systems of solvents and samples of different lots and preparative origins were examined and a rapid-scanning diode array UV detector (DAD) was particularly useful. With the proposed technique it was possible to identify 9 alpha-bromo desonide as a principal impurity, which was present in all examined samples of triamcinolone acetonide. This identification was rendered possible by the investigation of the second derivative of the UV spectra and by means of study of the mass spectrum. Furthermore, it was possible, primarily on the basis of the spectrophotometric data, to formulate reliable hypotheses on the possible identification of 9 beta, 11 beta-epoxide of the desonide which was present at very low levels and to exclude the presence of 11-deoxy-9(11)-unsaturated desonide. The presence of the above-mentioned related substances was explained considering the scheme of synthesis described in the literature. The spectrophotometric characteristics of the studied compounds and the limits of applicability of the present procedure are discussed.

The identification of related substances in 9 alpha-fluoroprednisolone-21 acetate by means of high-performance liquid chromatography with diode array detector and mass spectrometry.

A method for the analysis and identification of the principal related substances in 9 alpha-fluoroprednisolone acetate is described. This compound has been chosen as a model for the investigation of related substances which can be originated in the general procedure for introducing a fluorine substituent at position 9 of a corticosteroid molecule. HPLC procedures, both in reversed and in normal phase were used; a rapid scanning UV detector which allows direct spectrophotometric data to be obtained on chromatographic peaks, proved to be a tool of great importance. Thus, after reversed-phase chromatographic separation and observation of the UV spectra and their respective second derivatives, it was possible to characterize some of the principal effective and potential related substances such as 9 alpha-fluorohydrocortisone acetate, 9 alpha-bromoprednisolone acetate, 9 beta, 11 beta-epoxyprednisolone acetate and 9(11)-dehydroprednisolone acetate, emerging as chromatographic peaks. Identification of 9 alpha-bromoprednisolone acetate and of 9 alpha-fluorohydrocortisone acetate which proved to be the most significant impurities, was confirmed by means of an exhaustive study of the mass spectra of these substances conveniently isolated by normal-phase HPLC. The chromatographic, spectrophotometric and mass-spectrometric characteristics of the studied compounds are reported.

Analytical and regulatory considerations for ferritin-containing pharmaceutical products.

Ferritin, an iron-containing protein widely diffused in nature, has the important biochemical function of being the principal reserve and regulator for Fe3+ levels in blood and tissue. Due to its natural, effectively non-toxic iron content, ferritin has been the object of strong interest in the development of pharmaceutical products for use in iron deficiency treatment. Therefore, the need has arisen for the analytical characterization of this industrial product, be it in the hydroglyceric solution or dry powder form. The main considerations for the characterization of industrial ferritin are the following: a) iron content in both the unmodified product and the precipitated protein; b) protein content and protein/iron ratio; c) protein identification by means of polyacrylamide gel electrophoresis (PAGE); d) confirmation of protein identity and evaluation of molecular weight by means of size exclusion chromatography; e) identification and evaluation of other components of bulk ferritin preparations such as preservatives, excipients for lyophilization, water and concomitant proteins. Eight different samples were examined using the above considerations. Among the qualitative and quantitative results reported, of particular interest are those obtained by means of size-exclusion high performance liquid chromatography (SEC-HPLC). With a UV "diode array" detector it is possible to discern the peaks for ferritin and its molecular aggregates from those of concomitant proteins and preservatives; furthermore, it is possible to evaluate their molecular dimensions. Using this method, the ferritin monomer and other protein fractions can be quantitatively analyzed either by calculating area percent distribution of the chromatographic peaks or by comparing the sample with a highly pure external standard of ferritin.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotenoids, retinoids and alpha-tocopherol in human serum: Identification and determination by reversed-phase HPLC.

A rapid, simple and specific high performance liquid chromatographic procedure for assaying alpha- and beta-carotene is described. The method also enables the simultaneous determination of retinol and dl-alpha-tocopherol in human serum. The same chromatographic procedure can be used to assay the major carotenoids in human serum, provided analyses are replicated and the effluent is monitored at 450 nm. The conditions described also enable determination of licopene, cryptoxanthine and lutein with zeaxanthine. An aliquot of 0.5 ml serum is deproteinized with ethanol (0.5 ml) and extracted with petroleum ether (0.75 ml). The petroleum ether extract is evaporated until dry and then redissolved immediately with 0.5 ml of an eluent mixture consisting of methanol-hexane (85:15, v/v). Aliquots of 50 microl are then injected onto a 250 x 4.6 mm column packed with Spherisorb ODS-2. Owing to its good reproducibility, the procedure can be used for assays with external standards. Clinical applications are described for cases of hypercarotinemia associated with endocrine dysfunctions such as hypothyroidism and diabetes.

Quantitative analysis and purity evaluation of medroxyprogesterone acetate by HPLC.

A reversed-phase high-performance liquid chromatographic method was developed for the assay of medroxyprogesterone acetate and for the detection and determination of related steroids present as impurities in the drug. The method was compared with the normal-phase technique of the USP XX and was also applied to the analysis of tablets and injectable suspensions.

[Oral load test with beta-carotene in normal and dysthyroid subjects]. / La prova da carico per os con beta-carotene nei soggetti normali e distiroidei.

An oral load of beta-carotene (500 mg) was administered to four normal, four hypo and four hyperthyroid subjects. Plasma beta-carotene content was determined at the 2nd, 4th, 6th, 8th, 10th, 12th and 24th hour after administration and at every 24th hour thereafter for 5 consecutive days. Plasma assays were performed by HPLC. No significant differences were revealed by Student's T test for one group to the other. The authors sustain that, as there is no impairment in intestinal uptake of beta-carotene in disthyroid subjects, the elsewhere described increase in carotinemia in hypothyroids is due to other mechanisms.

[Effect of renal and liver failure on blood levels of vitamin A, its precursor (beta-carotene) and its carrier proteins (prealbumin and retinol binding protein)]. / Influenza dell'insufficienza renale ed epatica sul tasso ematico della vitamina A, dei suoi precursori (beta-carotene) e dei suoi vettori proteici (PA e RBP).

Plasma beta-carotene and retinol assay was performed by high pressure liquid chromatography (HPLC) in subjects with chronic renal failure or liver cirrhosis. In the same subjects blood prealbumin (PA) and retinol binding protein (RBP) were determined by immunological technique. A considerable increase of retinol and in a lesser extent of beta-carotene was noted in the blood of patients with renal insufficiency. In cirrhotic patients it was shown a marked decrease both of beta-carotene and retinol plasma concentrations. PA and RBP there were greatly increased in renal failure and decreased in liver cirrhosis. This results suggest that kidney and liver chronic failure interfere with vitamin A metabolism throughout their action on metabolic processes of synthesis and elimination of PA and RBP.

[Behavior of vitamin A, beta-carotene, retinol binding protein and prealbumin in the plasma of hypo- and hyperthyroid subjects]. / Comportamento della vitamina a, dela beta-carotene, della proteina legante il retinolo e della prealbumina nel plasma di soggetti ipo ed ipertiroidei.

Plasma concentrations of beta-carotene and retinol, determined by HPLC, and of transport proteins, ascertained by immunodiffusion technique, in hypo and hyperthyroid subjects are reported. In hypothyroid subject a considerable increase in carotene was noted. This was not the case for retinol. In hyperthyroids both beta-carotene and retinol levels were found to be normal. Transport protein (PA and RBP) levels were found to be lower only in cases of hyperthyroidism but unchanged for hypothyroids. According to the Authors the results show that the alteration in plasma carotene levels to be found in hypothyroid subjects is not the direct consequence of a lack of thyroid hormone in the metabolism of vitamin A but the indirect effect of thyroid disease.