Search

Background: Obesity and hypothyroidism are both common disorders within the general population. Obese hypothyroid subjects require higher doses of levothyroxine (LT4) compared with normal weight individuals. Previous studies on the effects of bariatric surgery on LT4 dose requirements in hypothyroid subjects have provided conflicting results. The aim of this study was to evaluate the LT4 requirements in a group of obese subjects with acquired hypothyroidism, before and after weight loss achieved by bariatric surgery., Methods: Ninety-three obese hypothyroid subjects (mean age = 48 ± 9 years; mean body mass index = 45.9 ± 5.6 kg/m(2)), were evaluated before and 28 ± 8 months after bariatric surgery. Changes in the LT4 dose, anthropometric measures, and hormone values were evaluated. In 20 patients, data of body composition, assessed by dual energy X-ray absorptiometry, were also analyzed., Results: On average, after weight loss, a significant reduction of the total dose of LT4 was documented (from 130.6 ± 48.5 to 116.2 ± 38.6 μg/day; p < 0.001). The LT4 dose had to be reduced in 47 patients, was unchanged in 34, and had to be increased in 12 patients affected by autoimmune thyroiditis. Reduction of the LT4 dose was proportional to reduction of the lean body mass., Conclusions: The weight loss achieved with modern surgical bariatric procedures is associated with a reduction of LT4 requirements in most hypothyroid subjects, which appears to be related to a decrease of the lean body mass. Occasionally, a concurrent decline of residual thyroid function, as it occurs in autoimmune thyroiditis, can counteract this phenomenon and eventually produce an increase of LT4 needs. It is believed that during the weight loss phase that follows bariatric surgery, there is no need for preventive adjustments of the LT4 dose, but serum thyroid hormones and thyrotropin should be periodically monitored in order to detect possible variations of LT4 requirements and to allow proper corrections of the therapy.

Background: Obesity is frequently associated with left ventricular hypertrophy (LVH), a condition leading to an increased cardiovascular risk., Aim: The objective of this study was to evaluate the prevalence of LVH in a cohort of obese women, with a main focus on the anthropometric and clinical parameters that are associated with an increased left ventricular mass (LVM)., Methods: The study was performed in 166 obese female patients. LVM was measured by echocardiography. The influence of various parameters on LVM was assessed by multivariate analysis., Results: The prevalence of LVH was drastically different depending on the type of indexed LVM, being 19.9% when the LVM was indexed for body surface area and 72.3% when indexed for height. Age, duration of obesity, weight, waist-to-hip ratio, pulse pressure and hypertension retained an independent direct correlation with the LVM, explaining 39.6% of the overall LVM variability. Among the parameters of the metabolic syndrome, the increase in blood pressure was the main determinant of increased LVM., Conclusions: By using allometric indexation of LVM for height, the results of our study indicate a high prevalence of LVH in a cohort of obese women. Hypertension, pulse pressure, age, duration of obesity, bodyweight and fat distribution, expressed as waist-to-hip ratio, predict 40% of LVM variation.

Background: Anesthesia is able to modulate the balance between proinflammatory and anti-inflammatory cytokine production during surgery. The aim of this study is to assess the effect of three anesthesia approaches, total intravenous anesthesia (TIVA), inhalation anesthesia, and xenon anesthesia, on sieric levels of nitric oxide (NO), IL6, IL10, and TNFα in obese patients undergoing Roux-en-Y laparoscopic gastric bypass., Methods: Thirty adult morbidly obese patients (BMI > 35) scheduled for Roux-en-Y laparoscopic gastric bypass were randomly recruited and allocated to TIVA (N = 10), inhalation anesthesia (SEV, N = 10), and xenon anesthesia (XE, N = 10). Exclusion criteria were ASA IV, age <18 or >60 years, and Mallampati IV. Opioid dosage and ventilation parameters were standardized. Sieric levels of NO, IL6, IL10, and TNFα were assessed at T0 (before induction of anesthesia), T1 (end of surgery), and T2 (12 h after the end of surgery). We compared the relative cytokine level variations (delta) at T1 and T2 and the cytokine exposure levels calculated as the area under the curve (AUC) between T0 and T2 in the XE and non-XE (SEV + TIVA) groups., Results: At T1, we found a significant ΔIL10 (reduction) and ΔTNFα (reduction) between XE and SEV (p < 0.05) and XE and TIVA (p < 0.05) groups. At T2, ΔIL10 was still significant. Furthermore, we found a reduced AUC value for TNFα in the XE group., Conclusions: Xenon anesthesia seems able to inhibit postoperative proinflammatory cytokine imbalance in morbidly obese patients undergoing Roux-en-Y laparoscopic gastric bypass; the reduced ΔTNFα at T1 and the reduced global exposition to TNFα in the XE group may explain the reduced ΔIL10 at T1 and T2.

A 54-year-old Italian female patient was admitted to our Department with the diagnosis of type 2 diabetes poorly controlled with insulin therapy. The patient was born by consanguineous parents (first degree cousins); she had acromegaloid features, diffuse lipoatrophy and muscular pseudo-hypertrophy since childhood. To confirm the clinical hypothesis of congenital generalized lipodystrophy (CGL) or Berardinelli-Seip syndrome, the sequences of AGPAT2 (encoding for 1-acyl-sn-glycerol-3-phosphate acyltransferase beta) and BSCL2 (encoding for seipin) candidate genes were analyzed. DNA analysis showed the presence of a homozygous mutation in exon 3 of the AGPAT2 gene (P112L). This is the first description of a Caucasian subject with CGL who carries the pathologic allelic variant P112L of the AGPAT2 gene.

Background: Bariatric surgery allows stable body weight reduction in morbidly obese patients. In presurgical evaluation, obesity-related co-morbidities must be considered, and a multidisciplinary approach is recommended. Precise guidelines concerning the endocrinological evaluation to be performed before surgery are not available. The aim of this study was to evaluate the prevalence of common endocrine diseases in a series of obese patients scheduled for bariatric surgery., Methods: We examined 783 consecutive obese subjects (174 males and 609 females) aged 18-65 years, who turned to the obesity centre of our department from January 2004 to December 2007 for evaluation before bariatric surgery. Thyroid, parathyroid, adrenal and pituitary function was evaluated by measurement of serum hormones. Specific imaging or supplementary diagnostic tests were performed when indicated., Results: The overall prevalence of endocrine diseases, not including type 2 diabetes mellitus, was 47.4%. The prevalence of primary hypothyroidism was 18.1%; pituitary disease was observed in 1.9%, Cushing syndrome in 0.8%, while other diseases were found in less than 1% of subjects. Remarkably, the prevalence of newly diagnosed endocrine disorders was 16.3%., Conclusions: A careful endocrinological evaluation of obese subjects scheduled for bariatric surgery may reveal undiagnosed dysfunctions that require specific therapy and/or contraindicate the surgical treatment in a substantial proportion of patients. These results may help to define the extent of the endocrinological screening to be performed in obese patients undergoing bariatric surgery.

The aim of this study was to investigate the clinical features of stomatognathic dysfunction in patients with rheumatoid arthritis (RA). The study sample consisted of 40 patients with RA (34 female, 6 male), mean age 44 years, recruited at the Rheumatology Division of the Department of Internal Medicine, University of Pisa, Italy. The inclusion criteria were diagnosis of RA according to the criteria of the American Rheumatism Association (ARA). In the study, 82.5% (n=33) of patients affected by RA satisfied at least the criteria of one diagnosis of temporomandibular disorders (TMD), according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The results are in agreement with the literature and the prevalence of such involvement ranges between 53% and 94% of patients. Several studies reported an involvement of the stomatognathic system in RA. In fact, RA can affect the temporomandibular joint as much as any other synovial joint. A more thorough analysis is required for a multidisciplinary approach to gnathological patients, including assessment by a rheumatologist. This issue and its epidemiologic relevance need further scientific research. Dentistry has a fundamental role in this process since patients who present with a systemic disease such as RA can be recognized and intercepted and referred to medical specialists, i.e., rheumatologists, to provide a diagnosis and therapy.

The current alarming spread of obesity in many parts of the world is caused by a sudden environmental shift characterized by replacement of a frugal diet with low cost, energy dense food, and little requests for physical activity during work and leisure time. Yet, not all people exposed to an obesogenic environment become obese, and individual differences in the propensity to gain weight as well as the occurrence of different obese phenotypes within the same environment indicate that the genetic heritage in this regard is significant and heterogeneous. The central melanocortin circuit has received much attention during the past decade, since mutations of genes expressing some key molecules in neurons of this system were discovered, which may cause monogenic forms of obesity in animals and humans. Within the arcuate nucleus of the hypothalamus the prohormone proopiomelanocortin is posttranslationally cleaved to produce the alpha-melanocyte stimulating hormone, a peptide with anorexigenic effects upon activation of the melanocortin-4 receptor (MC4R) expressed on the surface of target neurons. Studies regarding the frequency of MC4R mutations associated with human obesity have provided variable results (up to 6% of obese subjects). Various findings suggest an oligogenic and codominant mode of inheritance for MC4R deficiency, with modulation of expressivity and penetrance of the phenotype. The yield of MC4R testing in clinical diagnosis and treatment of obesity is at present undefined since the relatively low prevalence of MC4R pathogenic variants in the general population, along with the high number of sequence variants, has so far compromised the devising of systematic controlled intervention studies. Hopefully, in the future, MC4R testing will have practical implications for the development of new mechanism-based therapy of obesity as well as for the design of specific and more effective protocols, based on lifestyle intervention and current pharmacological or surgical approaches, for management of obesity in MC4R-mutated individuals.

Omega-3 fatty acids are essential polyunsaturated fatty acids that are crucial components of plasma membrane phospholipids. They influence cell structure and function and have anti-thrombotic and anti-arrhythmic properties, thus potentially exerting a favourable action on primary and secondary prevention of cardiovascular events. However, the supposed beneficial effect of omega-3 fatty acids in the management of cardiovascular risk has been evaluated only in a relatively small number of interventional studies, with results that are not consistent and are only suggestive of a putative beneficial effect of omega-3 supplementation on the prevention of cardiovascular mortality. Benefits have been reported mainly for the prevention of sudden death in patients with recent myocardial infarction and for primary and secondary prevention of nonfatal cardiac events in populations with high fish intake. Therefore, only ongoing trials will provide definitive data to elucidate whether omega-3 fatty acids could represent a new therapeutic approach for cardiovascular disease.

Data from controlled clinical studies comparing active drugs versus placebo or comparing different classes of drugs and their meta-analysis seem to indicate that although more subtle differences in the effects of various antihypertensive drugs cannot be ruled out, the protective effects against cardiovascular morbidity and mortality of all classes of drugs, including conventional therapy based on diuretics and beta-blockers and their combination, are largely explained by the extent of blood pressure (BP) reduction. Therefore BP control is still the main target of antihypertensive therapy. The benefits of diuretics have been well documented, particularly when these drugs are used at appropriate and/or optimal doses to achieve the optimal antihypertensive effect with the least occurrence of side effects, including negative metabolic effects. Therefore they must still be included among first line antihypertensive drugs. By contrast, beta-blockers seem recently to have lost their previously favored status as initial therapy for hypertension owing to their lower preventive effects against cardiovascular events as compared with diuretics in elderly hypertensive patients and against stroke as compared with other treatments, and to their negative metabolic effects. However, although evidence-based data must be taken into account, the choice of antihypertensive therapy aimed at BP control in individual patients must be made according to clinical characteristics. We believe that a wide range of choices among various antihypertensive drugs, above all diuretics and also beta-blockers, offers an appropriate possibility of selecting the right drug and the right combinations according to the clinical profile of the individual patient.

Several studies have reported an involvement of the stomatognathic system in the course of fibromyalgia (FM) similar to that which characterizes temporomandibular disorders (TMD). The aim of this study was to investigate and compare the clinical features of stomatognathic dysfunction in patients with FM and TMD. Ninety-three FM patients underwent an assessment according to the RDC/TMD guidelines. Prevalence of the different RDC/TMD diagnoses and some clinical parameters of FM patients were compared with those of 181 patients affected by TMD. Seventy-four (79.6%) FM patients presented at least one RDC/TMD diagnosis and showed lower mean maximum voluntary and passive mouth opening values than TMD patients. Moreover, 34 FM patients presented with trigger and/or tender points. Results of the present study confirm the high rate of involvement of the stomatognathic system in the course of FM and support the need for a careful multidisciplinary approach to patients with TMD, including the rheumatologist.

We report a real time study of the enthalpy release and heat capacity during the course of HCl-catalyzed hydrolysis of sucrose to fructose and glucose. Measurements were performed during both isothermal conditions and during slow heating and then cooling at a controlled rate. The reaction rate constant of the first-order kinetics follows an Arrhenius relation with activation energy of 109.2 kJ/mol of sucrose. On hydrolysis, the enthalpy decreases by 14.4 kJ/mol of sucrose at 310 K, and the heat capacity, Cp, increases by 61 J mol-1 K-1 of sucrose in the solution. The enthalpy of hydrolysis decreases with increase in the temperature and DeltaCp on hydrolysis increases. The effects are attributed to change in the configurational and vibrational partition functions as one covalent bond in sucrose breaks to form two molecules, which then individually form additional hydrogen bonds and alter the water's structure in the solution. Cp of the solution increases with temperature less rapidly before sucrose hydrolysis than after it. This may reflect an increase in the configurational contribution to Cp as the hydrogen bond population changes.

Background: The importance of psychosocial factors in the etiopathogenesis of temporomandibular disorders (TMD) has led to the hypothesis that these disorders may be part of a wider group of somatoform disorders, the functional somatic syndromes (FSS). Types of studies reviewed. The present paper is an overview summarizing the current concepts on the TMD-FSS relationship. A non-systematic search in the Medline database identified peer-reviewed papers on the epidemiological and clinical characteristics of the complex groups of disorders labelled functional somatic syndromes, focusing on the common features to temporomandibular disorders patients., Results: Literature data suggest that FSS and TMD share many etiopathogenetic and epidemiological features, both groups of disorders having a multifactorial etiopathogenesis and needing a multidisciplinary approach to diagnosis and treatment. Psychosocial characteristics of patients seem to have many similarities and the prevalence of Axis I psychiatric disorders is elevated. The majority of studies focused on the relationship between TMD and fibromyalgia (FM), due to the high rate of orofacial involvement related to FM. Clinical implications. The presence of common features between TMD and FSS patient may suggest the need for changes in the diagnostic and therapeutic approach to TMD patients, with the introduction of treatment protocols which also address the psychosocial impairment accompanying TMD symptoms, in order to overcome the limits of traditional therapies.

Several studies in the literature investigated the association between temporomandibular disorders (TMD) and otogenous symptoms, like vertigo, tinnitus, otalgia and muffling, although the question of the existence of a cause-effect relationship is still controversial. Epidemiological findings showed that the prevalence of ear symptomatology in the general population is variable from 10% to 31%, and increases up to 85% in TMD patients. Based on these data, many attempts have been performed to describe the physiopathological interactions between aural symptoms and TMD, as a strict anatomical link exists between the structures of the ear and those of the stomatognathic system. Unfortunately, methodological weaknesses of most studies are evident so that the comparison of results is often difficult. Considering these premises, the present study critically reviewed the literature on this debated issue, discussing the main etiopathogenetic hypotheses, the features of ear symptomatology in TMD patients and its relationship with TMD treatment in order to present current suggestions about the relationship between aural and TMD symptoms. Suggestions for future researches have been also presented, since a full understanding of this plausible interaction will be an important factor in diagnosis making and treatment planning for both pathologies.

The endothelium plays a crucial role in modulating vascular function and structure. In healthy conditions, nitric oxide produced by endothelial cells exerts not only vasodilating properties, but also several other protective actions toward the vessel wall against the development of atherosclerosis and thrombosis. Traditional cardiovascular risk factors are characterized by endothelial dysfunction caused by an enhanced production of oxidative stress leading to destroy nitric oxide, thus reducing its availability. Abdominal obesity is associated with endothelial dysfunction, through direct mechanisms, such as insulin resistance and the association with risk factors (including diabetes mellitus, hypertension and dyslipidemia), and direct, by the production of adipokines and pro-inflammatory cytokines, which in turn induce oxidative stress leading to a reduced nitric oxide availability. A reduced endothelium-dependent relaxation is a predictor of cardiovascular events in high-risk patients and represents a putative clinical parameter to stratify the cardiovascular risk and a useful marker for therapy efficacy. Weight loss and a modification of lifestyle ameliorate endothelial function in obese patients, an effect due not only to a better glycemic profile, but also secondary to reduced plasma levels of inflammatory markers and adipokines. At present, whether an improvement of endothelial dysfunction secondary to weight loss is significantly associated with a better cardiovascular prognosis is still unknown. (G Ital Cardiol 2006; 7 (11): 715-723)

Heat capacity of controlled amounts of water in Vycor's 2 nm radius pores has been determined in real time during the course of water's isothermal nanoconfinement from bulk state at 358 K, by using temperature-modulated calorimetry. As water transfers from bulk to nanopores via the vapor phase, its heat capacity per molecule increases asymptotically toward a limiting value of 1.4 times the heat capacity of bulk water for 1.8 wt % water in Vycor and 1.04 times for 10.0 wt %. The observations indicate that vibrational and configurational contributions to the heat capacity are highest when the amount of water is insufficient to completely cover the pore wall, and they decrease as more water is present in the nanopores and water clusters form. The heat capacity of water in completely filled nanopores approaches the value for bulk water, thus indicating that the heat capacity varies with the water molecules' position in the nanopores.

The heat capacity C(p) of the liquid state of water confined to 2 nm radius pores in Vycor glass was measured by temperature modulation calorimetry in the temperature range of 253-360 K, with an accuracy of 0.5%. On nanoconfinement, C(p) of water increases, and the broad minimum in the C(p) against T plot shifts to higher temperature. The increase in the C(p) of water is attributed to an increase in the phonon and configurational contributions. The apparent heat capacity of the liquid and partially frozen state of confined water was measured by temperature scanning calorimetry in the range of 240-280 K with an accuracy of 2%, both on cooling or heating at 6 K h(-1) rate. The enthalpy, entropy, and free energy of nanoconfined liquid water have been determined. The apparent heat capacity remains higher than that of bulk ice at 240 K and it is concluded that freezing is incomplete at 240 K. This is attributed to the intergranular-water-ice equilibrium in the pores. The nanoconfined sample melts over a 240-268 K range. For 9.6 wt % nanoconfined water concentration ( approximately 50% of the maximum filling) at 280 K, the enthalpy of water is 81.6% of the bulk water value and the entropy is 88.5%. For 21.1 wt % (100% filling) the corresponding values are 90.7% and 95.0%. The enthalpy decrease on nanoconfinement is a reflection of the change in the H-bonded structure of water. The use of the Gibbs-Thomson equation for analyzing the data has been discussed and it is found that a distribution of pore size does not entirely explain our results.

Objectives: We assessed whether third-generation oral contraceptive (OC) treatment (30 microg ethinylestradiol + 75 microg gestodene daily) could affect the endothelial function of healthy women., Methods: In 20 young healthy women (HW) and 10 hypercholesterolemic women (CW) we assessed forearm blood flow (strain-gauge plethysmography) changes induced by the intrabrachial infusion of acetylcholine (ACH) (0.15-15 microg/100 ml forearm tissue/min) and sodium nitroprusside (SNP) (1-4 microg/100 ml forearm tissue/min). ACH was repeated during the nitric oxide synthase inhibitor intra-arterial NG-monomethyl-L-arginine (L-NMMA) (100 microg/100 ml forearm tissue/min) or the antioxidant vitamin C (8 mg/100 ml forearm tissue/min). HW repeated the protocol after 6-month OC (n = 10) or placebo (n = 10) treatment., Results: In HW the maximal vasodilation to ACH, similar between placebo and OC subgroups, was significantly reduced in CW (P < 0.01). Vasodilation to ACH was blunted (P < 0.01) by L-NMMA and unaffected by vitamin C, in both OC and placebo groups. In CW the vasodilation to ACH, not modified by L-NMMA, was improved by vitamin C (P < 0.01). OC treatment raised (P < 0.01) plasma total and low-density lipoprotein cholesterol, and values were similar to those shown by CW. Both OC and placebo intake did not change the response to ACH and the modulation induced by L-NMMA or vitamin C. Vasodilation to SNP was similar in all groups., Conclusions: In HW 6-month treatment with third-generation OC, although associated with an abnormal lipid profile, does not adversely affect endothelium-dependent vasodilation. This neutral effect could be the balance between a deleterious effect of hypercholesterolemia and a protective effect of OC on endothelial function.

Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxidative stress-induced nitric oxide (NO) breakdown and compensatory production of a hyperpolarizing factor. To test whether calcium antagonist treatment can restore NO availability and prevent hyperpolarization through antioxidant properties, in 15 healthy subjects and 15 patients with essential hypertension, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial bradykinin (5, 15, 50 ng/100 mL per minute), an endothelium-dependent vasodilator, in basal conditions, during infusion of NG-monomethyl-l-arginine (L-NMMA, 100 microg/100 mL per minute), an NO-synthase inhibitor, and ouabain (0.72 microg/100 mL per minute), an Na+-K+ ATPase inhibitor to prevent hyperpolarization. These infusions were repeated in the presence of the antioxidant vitamin C (8 mg/100 mL/min). The response to sodium nitroprusside was also evaluated. In controls, vasodilation to bradykinin was inhibited by L-NMMA and remained unchanged by ouabain or vitamin C. In hypertensive patients, vasodilation to bradykinin was blunted and resistant to L-NMMA but sensitive to ouabain. Vitamin C increased the response to bradykinin and restored the inhibiting effect of L-NMMA while preventing the effect of ouabain. In hypertensive patients, infusions were repeated after 3-month treatment with lercanidipine (10 to 20 mg daily). Lercanidipine decreased plasma lipoperoxides, isoprostanes, and malondialdehyde and increased plasma antioxidant capacity. Moreover, lercanidipine increased the vasodilation to bradykinin and restored the inhibiting effect of L-NMMA on bradykinin-induced vasodilation while preventing the effect of ouabain. Finally, vitamin C no longer exerted its facilitating activity. These results indicate that in essential hypertension, lercanidipine increases endothelium-dependent vasodilation by restoring NO availability and preventing hyperpolarization, an effect probably determined by antioxidant activity.

Homocysteine is an intermediate sulfur-containing amino acid formed during intracellular metabolism of methionine. Circulating homocyst(e)ine can be increased by genetic deficiency of enzymatic pathways involved in its catabolism as well as by environmental factors including nutritional deficiencies, life style factors, physiological conditions, drugs and some diseases, which mainly induce deficiency of folate, vitamin B12 and vitamin B6. Therefore plasma homocyst(e)ine can be reduced by vitamin therapy with folate and vitamin B12. Although hyperhomocyst(e)inemia exerts a prothrombotic and proatherosclerotic effect, its relevance in the genesis of the atherosclerotic lesions, as well in the first occurrence of cardiovascular events in normotensive and even more so in hypertensive patients is still to be established. However available data indicate that hyperhomocyst(e)inemia could be an independent risk factor for the recurrence of cardiovascular events in patients with coronary artery disease and in elderly high risk patients. Finally, the possibility that a reduction in plasma homocyst(e)ine induced by vitamin therapy can diminish the risk of cardiovascular events is under evaluation in several controlled longitudinal studies focusing mainly on secondary prevention.

Objectives: We sought to evaluate whether fasting hyperhomocystinemia reduces endothelial function by oxidative stress in normotensive subjects and hypertensive patients., Background: Subjects with hyperhomocystinemia have endothelial dysfunction., Methods: In 23 normotensive subjects and 28 hypertensive patients, classified into normohomocystinemic and hyperhomocystinemic groups according to homocysteine plasma levels (< 8.7 and >14.6 micromol/l, respectively), we studied forearm blood flow changes (strain-gauge plethysmography) induced by intrabrachial administration of acetylcholine (0.15 to 15 microg/100 ml tissue per min) or sodium nitroprusside (1 to 4 microg/100 ml per min), an endothelium-dependent and -independent vasodilator, respectively. Acetylcholine was repeated with N(G)-monomethyl-L-arginine (L-NMMA; 100 microg/100 ml per min), vitamin C (8 mg/100 ml per min) and L-NMMA plus vitamin C., Results: Normotensive hyperhomocystinemic patients showed a blunted response to acetylcholine and a lower inhibiting effect of L-NMMA on acetylcholine, as compared with normohomocystinemic patients. Although vitamin C was ineffective in normohomocystinemic subjects, it increased the response to acetylcholine and restored the inhibiting effect of L-NMMA on acetylcholine in hyperhomocystinemic patients. Hypertensive hyperhomocystinemic patients showed a reduced response to acetylcholine, as compared with normohomocystinemic subjects. In both subgroups, L-NMMA failed to blunt the response to acetylcholine. The potentiating effect of vitamin C on acetylcholine was greater in hyperhomocystinemic patients than in normohomocystinemic subjects, although it restored the inhibitory effect of L-NMMA on acetylcholine-induced vasodilation to the same extent in both groups. Hyperhomocystinemia did not change the response to sodium nitroprusside., Conclusions: In normotensive subjects and hypertensive patients, hyperhomocystinemia impairs endothelium-dependent vasodilation. It could be related to oxidant activity.

Age-related endothelial dysfunction could be caused by an alteration in the L-arginine-NO system and the production of oxidative stress in both normotensive and hypertensive individuals. In 47 normotensive subjects and 49 patients with essential hypertension, we evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial sodium nitroprusside (1, 2, and 4 microg/100 mL per minute) and acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-independent vasodilator and an endothelium-dependent vasodilator, respectively. Acetylcholine was repeated in the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or both. Vasodilation to acetylcholine, but not to sodium nitroprusside, was lower (P<0.01) in hypertensive patients compared with control subjects. Moreover, in both groups, endothelium-dependent vasodilation declined with aging. In normotensive subjects, the inhibiting effect of L-NMMA on response to acetylcholine decreased in parallel with advancing age, whereas vitamin C increased vasodilation to acetylcholine in only the oldest group (age >60 years). In young hypertensive patients (age <30 years), vasodilation to acetylcholine was sensitive to L-NMMA, whereas in hypertensive patients age >30 years, vitamin C enhanced endothelium-dependent vasodilation and restored the inhibiting effect of L-NMMA on response to acetylcholine. In normotensive individuals, an earlier primary dysfunction of the NO system and a later production of oxidative stress cause age-related reduction in endothelium-dependent vasodilation. These alterations are similar but anticipated in hypertensive patients compared with normotensive subjects.

Background: Aging is associated with increased cardiovascular risk and endothelial dysfunction. Since exercise can improve endothelium-dependent vasodilation, in the present study we tested whether long-term physical activity could prevent aging-related endothelial dysfunction., Methods and Results: In 12 young and elderly (age 26.9+/-2.3 and 62.9+/-5.8 years, respectively) healthy sedentary subjects and 11 young and 14 elderly matched athletes (age 27.5+/-1.9 and 66.4+/-6.1 years, respectively), we studied (with strain-gauge plethysmography) forearm blood flow modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator, at baseline, during infusion of N(G)-monomethyl-L-arginine (L-NMMA) (100 microg/100 mL forearm tissue per minute), a nitric oxide-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), an antioxidant, and finally under simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (1, 2, and 4 microg/100 mL forearm tissue per minute) was also evaluated. In young athletes and sedentary subgroups, vasodilation to acetylcholine was inhibited by L-NMMA and was not changed by vitamin C. In elderly subjects, vasodilation to acetylcholine was blunted as compared with young subjects in both control subjects and athletes, whereas the response to sodium nitroprusside was similar. Moreover, in elderly athletes, vitamin C did not change the vasodilation to acetylcholine. In contrast, in elderly sedentary subjects, the response to acetylcholine was resistant to L-NMMA. In this subgroup, vitamin C increased the vasodilation to acetylcholine and restored the inhibiting effect of L-NMMA., Conclusions: These results suggest that regular physical activity can at least in part prevent the age-induced endothelial dysfunction, probably the restoration of nitric oxide availability consequent to prevention of production of oxidative stress.

Endothelium can deeply influence vascular tone and structure. The main endothelium derived factor is nitric oxide, which is not only a potent vasodilator but also inhibits platelet aggregation, smooth muscle cell migration and proliferation, monocyte adhesion and adhesion molecule expression, thus protecting the vessel wall against the development of atherosclerosis and thrombosis. In human hypertension, endothelial dysfunction has been documented in peripheral and coronary macro and microcirculation and in renal circulation. Impaired endothelium-dependent vasodilation associated with essential hypertension seems to be a primary phenomenon, since it can be detected in the offspring of essential hypertensive patients, shows no clear correlation with blood pressure value, and is not normalized by the mere reduction of blood pressure. The phenomenon responsible for endothelial alteration in essential hypertensive patients seems to be the activation of an alternative pathway involving cyclooxygenase which reduces NO availability through production of oxidative stress. This alteration in the NO pathway could be the main mechanism through which a dysfunctional endothelium could be a promoter of atherosclerosis and thrombosis in essential hypertension.

A generalized study has been done of the transmission characteristics of a Fabry-Perot interferometer (FPI) illuminated by a Gaussian light beam impinging on it at normal and non-normal incidence. The theoretical approach is based on a plane-wave, angular-spectrum representation of both the incident Gaussian beam and the transmitted beam. Expressions are obtained for the FPI instrumental function and for the spatial distribution of the transmitted beam. Numerical results are presented for the FPI maximum transmission, effective finesse, and spectral displacement of the interference maximum.

The effect of reflective multipass interferometers on the transverse modes of laser cavities equipped with these devices is investigated. We demonstrate, both theoretically and experimentally in a pulsed CO(2) laser, how information on the characteristics of these modes can be directly derived by simply describing these cavities in terms of suitable equivalent geometric parameters. We also discuss and explain the transverse-mode selective properties of these multimirror cavities.

We present the results of intrapulse frequency chirping measurements that were carried out on a TEA CO(2) laser equipped with various conventional and unconventional frequency-selective optical cavities. We experimentally demonstrate that there is a close relationship between the causes and the extent of intrapulse frequency chirping on the one hand and the type of optical configuration that is used for controlling the laser mode behavior on the other. In particular, it is shown that intrapulse chirping of the emitted frequency can be significantly reduced by employing laser cavities terminating in high-finesse reflective multipass interferometers for single-mode selection. In fact, this type of cavity can be designed in such a way to minimize the effects on the emitted frequency of perturbations affecting the cavity optical length.