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The authors propose a novel surgical technique for reconstruction of full-thickness defects of the middle portion of the auricle including the helix and the antihelix up to the neighboring portion of the concha and sparing the whole of the ear lobe. It is a single-stage procedure that is indicated when a large, redundant, and pendulous earlobe exists as typically occurs in the elderly patient. The earlobe is rotated into the full-thickness ear defect and fits as an inlay between two cartilaginous stumps. The ear lobe presents two anatomical patterns: the pendulous or free one, with the ear lobe lying free from the cheek, and the non-pendulous or attached one, where the ear lobe is attached to the cheek. Donor site deformity is therefore limited to the conversion of a pendulous ear lobe pattern into an attached one. Surgery may be scheduled in an outpatient basis as the procedure is easy to plan, is fast to perform, and is carried out under local anesthesia.Level of Evidence: Level IV, therapeutic study. [ABSTRACT FROM AUTHOR]

Summary 1 Inflammatory bowel disease (IBD) is a condition that involves proinflammatory cytokines such as interleukins 1β and 6 (ILs). In this disease, it has been shown that an abnormal microcirculatory system is implicated. 2 Therefore, the effects of in vivo treatment for three days with interleukins 1β and 6 were investigated on rat isolated mesenteric vascular bed (MVB). 3 A significant concentration-dependent increase in vascular response to noradrenaline (NA) was found, with a significant difference in E[sub max] between control (93.01 ± 16.78 mmHg) and treated preparations (137.91 ± 5.20 mmHg). Endothelin-1(ET-1) induced a significantly greater increase of perfusion pressure in treated rats in comparison with control rats at the highest concentration used (0.1 μ m). 4 The concentration-dependent decrease of perfusion pressure induced by acetylcholine (ACh) in MVB precontracted with NA was significantly reduced in specimens from treated rats in comparison with control rats, with a significant difference in E[sub max] between control and treated preparations. 5 Perivascular nerve stimulation (PNS) evoked contractions with no difference between treatments. Similarly, no difference in relaxant effect was found after PNS in specimens precontracted with NA, in the presence of guanethidine. 6 These findings indicate that the precocious inflammation acts only at postsynaptic level, facilitating vascular contraction. These data seem to support the hypothesis that vascular dysfunction caused by overproduction of ILs may contribute, among other immunological factors, to vasculitis in IBD that leads to intestinal ischaemia through vasoconstriction. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a recognized risk factor for cardiovascular diseases (eg, myocardial infarction, stroke, arrhythmias, coronary events, heart failure) and for progression of renal disease. In 1995, a new class of antihypertensive drugs--angiotensin II (AII)-receptor blockers (ARBs)--became available for treatment.Objectives: In this retrospective study, we aimed to (1) determine the frequency of prescriptions for ARBs compared with those for all other antihypertensive drugs and (2) examine the indications for, and profile of, the use of ARBs in antihypertensive pharmacotherapy over a 2-year period (July 1997-June 1999).Methods: Medical records of patients who were being treated for the first time at the Division of Hypertension, University of Bari Medical School (Bari, Italy) were included. The investigators analyzed the medical records of patients with grade 1, 2, or 3 essential hypertension, as well as those with a history of essential hypertension whose blood pressure had been normalized by treatment before this first visit and who were already receiving antihypertensive drugs or who were being prescribed antihypertensive drugs for the first time at this visit.Results: The medical records of 880 patients (466 women, 414 men; mean [SD] ages, 55.0 [10.8] and 53.6 [11.3] years, respectively) were included in the study. ARBs accounted for 6% of all antihypertensive prescriptions. No correlation was found between receiving a prescription for an ARB and sex, age group, heart rate, or body mass index. ARB monotherapy was inversely correlated (P < 0.05) with the grade of hypertension. ARBs were prescribed more often during year 2 than year 1 of the study (7.7% vs 4.4%, respectively; P < 0.02). This increase coincided with a significant decrease in all other antihypertensive prescriptions taken together (P < 0.02).Conclusions: The results of this study indicate that although ARBs were prescribed infrequently and cautiously, their prescription rate increased over time, suggesting that this medication is gaining acceptance as treatment for hypertension. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a recognized risk factor for cardiovascular diseases (eg, myocardial infarction, stroke, arrhythmias, coronary events, heart failure) and for progression of renal disease. In 1995, a new class of antihypertensive drugs—angiotensin II (AII)-receptor blockers (ARBs)—became available for treatment.Objectives: In this retrospective study, we aimed to (1) determine the frequency of prescriptions for ARBs compared with those for all other antihypertensive drugs and (2) examine the indications for, and profile of, the use of ARBs in antihypertensive pharmacotherapy over a 2-year period (July 1997–June 1999).Methods: Medical records of patients who were being treated for the first time at the Division of Hypertension, University of Bari Medical School (Bari, Italy) were included. The investigators analyzed the medical records of patients with grade 1, 2, or 3 essential hypertension, as well as those with a history of essential hypertension whose blood pressure had been normalized by treatment before this first visit and who were already receiving antihypertensive drugs or who were being prescribed antihypertensive drugs for the first time at this visit.Results: The medical records of 880 patients (466 women, 414 men; mean [SD] ages, 55.0 [10.8] and 53.6 [11.3] years, respectively) were included in the study. ARBs accounted for 6% of all antihypertensive prescriptions. No correlation was found between receiving a prescription for an ARB and sex, age group, heart rate, or body mass index. ARB monotherapy was inversely correlated (P < 0.05) with the grade of hypertension. ARBs were prescribed more often during year 2 than year 1 of the study (7.7% vs 4.4%, respectively; P < 0.02). This increase coincided with a significant decrease in all other antihypertensive prescriptions taken together (P < 0.02).Conclusions: The results of this study indicate that although ARBs were prescribed infrequently and cautiously, their prescription rate increased over time, suggesting that this medication is gaining acceptance as treatment for hypertension. [Copyright &y& Elsevier]

Resveratrol (3,5,4′-trihydroxystilbene) is a natural occurring molecule, synthesized by plants in response to different stresses. Recent literature data seem to converge in indicating Resveratrol as an agent possessing protective effects against oxidative stresses through different mechanisms. Furthermore conflicting data are present in relation to its activity of free radical scavenger. Here we studied the antioxidant activity actually exerted by the agent against reactive oxygen species induced by H2O2 treatments in CHO cells. Our attention has been focused on two major potential mechanisms: scavenging activity and interference with oxidative metabolism, by the analysis of three important targets: intracellular oxidation (Dichlorofluorescein Test), primary DNA damage (Comet Assay) and fixed DNA damage (chromosomal aberrations). Cells were treated with a single H2O2 dose (2×10−4 M) in order to induce Reactive Oxygen Species and than challenged with Resveratrol to test its ability in modulating damage. Two experimental protocols have been applied: (i) simultaneous treatment and (ii) a 3 h Resveratrol pre-treatment. In our experimental conditions Resveratrol does not appear able, ‘per se’, to induce primary DNA damage whereas a slight increase in endogenous oxidation and chromosomal aberrations at the highest dose have to be noticed. In combined treatments the molecule appears to differently affect primary and fixed DNA damage. [Copyright &y& Elsevier]

Focuses on a study which described the clinical, immunological and genetic features of lean newly diagnosed diabetic patients. Research design and methods; Results; Conclusions.

In healthcare systems of developed countries, obtaining informed consent is a necessary and fundamental requirement for the administration of any medical treatment. In Italy, for the administration of the recipient's informed consent for a blood transfusion, a pre-printed form is used in line with the Decree of the Ministry of Health dated 2 November 2015. This paper aims to analyse this form in light of the European legal provisions and following the enactment of Italian Law No. 219 of 2017 on informed consent and advance treatment directives. Our review shows that the structure of the form can be improved in light of the new direction provided by Italian law, the scientific advancement on transfusion risks, and the potential to reduce the use of blood components. Revising this form could be the opportune time to include written information on Patient Blood Management strategies. Though not exhaustive, this proposal may stimulate debate on the point and produce further contributions. [ABSTRACT FROM AUTHOR]

Background Stress during a pandemic increases the risk of alcohol consumption, which may require pharmacological management. Methods An observational single-center retrospective study was conducted from 1 January 2018 to 31 December 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the emergency departments (EDs) of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ESs) who were either admitted or not admitted, due to their refusal. Results A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, an inverse association was found between pharmacological treatment and number of calls coded green (non-critical) and yellow (fairly critical) in patients admitted to EDs. An inverse association was also found for calls coded green in patients not admitted to EDs and pharmacological treatment. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. Conclusions ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs. [ABSTRACT FROM AUTHOR]

The association of obesity and diabetes, termed “diabesity”, defines a combination of primarily metabolic disorders with insulin resistance as the underlying common pathophysiology. Cardiovascular disorders associated with diabesity represent the leading cause of morbidity and mortality in the Western world. This makes diabesity, with its rising impacts on both health and economics, one of the most challenging biomedical and social threats of present century. The emerging comprehension of the genes whose alteration confers inter-individual differences on risk factors for diabetes or obesity, together with the potential role of genetically determined variants on mechanisms controlling responsiveness, effectiveness and safety of anti-diabetic therapy underlines the need of additional knowledge on molecular mechanisms involved in the pathophysiology of diabesity. Endothelial cell dysfunction, resulting from the unbalanced production of endothelial-derived vascular mediators, is known to be present at the earliest stages of insulin resistance and obesity, and may precede the clinical diagnosis of diabetes by several years. Once considered as a mere consequence of metabolic abnormalities, it is now clear that endothelial dysfunctional activity may play a pivotal role in the progression of diabesity. In the vicious circle where vascular defects and metabolic disturbances worsen and reinforce each other, a low-grade, chronic, and ‘cold' inflammation (metaflammation) has been suggested to serve as the pathophysiological link that binds endothelial and metabolic dysfunctions. In this paradigm, it is important to consider how traditional antidiabetic treatments (specifically addressing metabolic dysregulation) may directly impact on inflammatory processes or cardiovascular function. Indeed, not all drugs currently available to treat diabetes possess the same anti-inflammatory potential, or target endothelial cell function equally. Perspective strategies pointing at reducing metaflammation or directly addressing endothelial dysfunction may disclose beneficial consequences on metabolic regulation. This review focuses on existing and potential new approaches ameliorating endothelial dysfunction and vascular inflammation in the context of diabesity. [ABSTRACT FROM AUTHOR]

Abstract: Assessing biological age in the youth nearby legal age has always represented a stimulating issue for the Italian forensic scientist as far as he deals with matter of imputability and legal or illegal immigration of uncertain age subjects. Since any method of evaluation should of course be accurate, not invasive, reproducible and, as possible, easily exploitable, radiological investigation of age dependent features is the most appropriate instrument to the purpose. Dental development is slower and delayed compared with skeletal bone one, occurring according to a known, regular pattern from whose evaluation a biological age can be assessed with a reasonably restricted span for a certain radiological image. This is the assumption which inspired since 1941 (Schour e Massler) so many anthropologists and forensic and clinic odontologist in investigating biological age by the study of radiological dental morphology. Demirjian and Goldstein [New systems for dental maturity based on seven and four teeth, Ann. Hum. Biol. 3 (1976) 411–421] obtained no differences between two groups of subjects whose age was extimated by the evaluation of 14 teeth in one case and 7 teeth in another, the last being greatly simpler. Afterwards, Thorson (1991), Mincer et al. [The A.B.F.O. study of third molar development and its use as estimator of chronological age, J. Forensic Sci. 38 (1993) 379], Solari and Abramovitc [The accuracy and precision of third molar development as an indicator of chronological age in Hispanic, J. Forensic Sci. (3) (2002) 531–535] and then Prieto Carrero [Evaluation of Chronological Age Based on Third Molar Development in the Spanish Population, Atti del XIX Congresso IALM, Milano, 2003], developed a method based on the evaluation of the radiological development of the alone third molar, according to Demirjian''s schematic definitions of crown and root formation. Eight stages of development of the third molar are defined from the time of mineralization appearance of the cusp tips up to complete closing of the apexes. In order to achieve grater precision in discriminating stages F and G, Solari added two stages (F1 and G1), determining 10 stages of maturation of root and crown. Prieto tested the accuracy and precision of this method by the evaluation of about 1300 orthopantomographs of juveniles and young Spanish adults of known age, divided for gender. We analyzed a total of 400 orthopantograms of young Spanish dental patients to evaluate the chronology of the right mandibular third molar development and to assess its correlation with the biological age of the tested. Biological age is attributed with a maximum standard deviation of 2.47 from the mean in the eight stages outline. The greatest limit of the method seems to be the operator experience in determining the dental stage of development. We think that age data coming from such evaluation method should be clearly explained to the magistrate in their true statistical significance and limits. [Copyright &y& Elsevier]

Background: Coronary chronic total occlusion lesions (CTOs) confer an increased risk of arrhythmic events among patients with ischemic cardiomyopathy (ICM) and implantable cardioverter-defibrillator (ICD) carriers, however the impact of CTO recanalization in this population remains unassessed.Aims: Evaluate the impact of CTOs percutaneous coronary interventions (PCI) on arrhythmic events.Methods: Patients with ICM and ICD from the VACTO I-II registries: patients with medically treated CTO (CTO-OMT group) and without CTO (no-CTO group) were compared after inverse-probability-weighting adjustment (IPWT) with a similar population of consecutive patients undergoing CTO-PCI. The primary endpoint was appropriate ICD therapy. The secondary endpoint was all-cause mortality.Results: The total of 622 patients (mean age 67 ± 10 years, mean left ventricular ejection fraction 36 ± 11%) included in the analysis was composed by: CTO-PCI patients n = 113, CTO-OMT patients n = 286, no-CTO patients n = 223. In the CTO-PCI group, compared to the CTO-OMT group, 5-year Kaplan Meier estimates for appropriate ICD therapy (20.4% vs. 56.4%, IPW-adjusted HR: 0.45, 95% CI 0.29-0.71) and mortality (8.8% vs. 23%, IPW-adjusted HR: 0.43, 95% CI 0.22-0.85) were lower, driven by infarct related artery CTO (IRA-CTO) PCI, while similar to those occurring in the no-CTO group.Conclusions: In this large population, those with CTO receiving PCI had lower arrhythmic event rates and lower mortality compared to the CTO-OMT group, while showing an event rate similar to no-CTO patients. Sensitivity analyses suggest that the beneficial effect on the arrhythmic outcome was driven by IRA-CTO revascularization.Classification: Chronic total occlusion. [ABSTRACT FROM AUTHOR]

The aim of the paper was to perform a chronological assessment of the phenomenon of delayed rupture of the spleen, to assess the phenomenological order about the sub-capsular hematoma transformation to determine the causal relationship with trauma as hypothetical cause of death. 80 cases of blunt trauma with splenic capsular hematoma and subsequent rupture of the spleen were evaluated: 38 had an acute rupture of the spleen, 42 presented a break in days or weeks after the traumatic injury. Time between the traumatic event and delayed rupture of the spleen is within a range of time from one day to more than one month. Data recorded included age, sex, type of trauma, injury severity score, grade of splenic injury, associated intra-abdominal injuries, pathologic specimen evaluation. Immunohistochemical investigation of perisplenic hematoma or laceration was performed utilizing polyclonal antibodies antifibrinogen, CD61 and CD68, and showed structural chronological differences of sub-capsular hematoma. Expression of modification and organization of erythrocytes, fibrinogen, platelets and macrophages provides an informative picture of the progression of reparative phenomena associated with subcapsular hematoma and subsequent delayed splenic rupture. Sub-capsular splenic hematoma dating, which we divided into 4 phases, is representing a task in both clinical practice and forensic pathology. [ABSTRACT FROM AUTHOR]

Abstract: Earlier neuroimaging studies of motor function in schizophrenia have demonstrated reduced functional lateralization in the motor network during motor tasks. Here, we used event-related functional magnetic resonance imaging during a visually guided motor task in 18 clinically unaffected siblings of patients with schizophrenia and 24 matched controls to investigate if abnormal functional lateralization is related to genetic risk for this brain disorder. Whereas activity associated with motor task performance was mainly contralateral with only a marginal ipsilateral component in healthy participants, unaffected siblings had strong bilateral activity with significantly greater response in ipsilateral and contralateral premotor areas as well as in contralateral subcortical motor regions relative to controls. Reduced lateralization in siblings was also identified with a measure of laterality quotient. These findings suggest that abnormal functional lateralization of motor circuitry is related to genetic risk of schizophrenia. [Copyright &y& Elsevier]

Indomethacin-induced enteritis is a model of inflammatory bowel disease.To further characterize this model, rats received two injections of indomethacin (7·5 mg kg−1) 24 h apart and histological damage of intestinal mucosa, oxidative stress, alterations of intestinal motility and mesenteric vascular bed (MVB) reactivity were investigated after 5 days.The results show that indomethacin caused several histological and functional changes at the ileal level. In particular, response to carbachol as well as the nonadrenergic-noncholinergic inhibitory response to electrical field stimulation (EFS) was lower in the treated than control rats. Moreover, nitric oxide (NO)-component of the inhibitory response was higher in the treated than control rats. Mesenteric vessels preparations from the treated rats showed increased noradrenaline (NA)-induced perfusion pressure, whereas relaxant responses to acetylcholine, although not significantly reduced in the treated rats, had a higher nitrergic component. This finding suggests that vascular dysfunction may contribute to chronic inflammation. Indomethacin injection also determined acute and severe oxidative stress in ileum mucosa.In conclusion, our study contributes to further characterize the rat model of indomethacin-induced enteritis and suggests that it is suitable for drug screening in rats, as this model can be obtained in a very short period and is simple and reproducible.Eur J Clin Invest 2005; 35 (4): 271–278 [ABSTRACT FROM AUTHOR]

Abstract Background In rodents, interleukins administration induces intestinal changes similar to those found in inflammatory bowel disease. We investigated the effects of in vivo subchronic treatment with IL-1 beta and IL-6 on rat colonic mucosa and circular smooth muscle. Materials and method We evaluated transmucosal electrical parameters (Ussing chambers) and early changes of in vitro direct contractility induced by carbachol and tachykinins. Alterations in excitatory and inhibitory neurotransmission were studied with electrical field stimulation (EFS). Results Treatment with interleukins induces inflammation proved by fever, early signs of colonic histological damage and changes in mucosal ion transport. Concentration response-curve to carbachol was significantly lower in treated rats (P < 0·02) with significant difference in Emax between control (1·67 ± 0·17 g) and treated preparations (1·20 ± 0·13 g) (P < 0·05). Concentration response-curve to NK2 agonist was significantly lower in the treated rats (P < 0·005) with a significant difference in Emax between the control (0·26 ± 0·04 g) and treated preparations (0·12 ± 0·02 g) (P < 0·02). None of the drugs used induces changes in EC50 . The contractile reflex response to electrically induced distension was significantly higher in the treated rats and more reduced after administration of atropine. Adding NK2 receptor antagonist resulted in a further reduction being observed in the treated and control rats (P = NS). Relaxation by EFS on cholinergic tone was not different between treatments, although pretreatment with L-NNA resulted in greater relaxation in the treated (-21·7%) than in the control rats (-14·8%). Conclusion Early inflammation induced by a subchronic treatment with ILs causes changes in mucosal ionic transport parameters, a reduction in the direct... [ABSTRACT FROM AUTHOR]

Investigates the effect of endothelial cyclooxygenase (COX)-1 and -2 on the reactivity of the mesenteric vascular bed (MVB) in portal hypertensive rats. Expression of constitutive and inducible COX; Role of prostanoids in the aorta in the MVB; Data suggesting that generation of endothelial vasodilator prostanoids accounts for the increased mesenteric blood flow in portal hypertension.

Background: Adiponectin (AD) cardioprotective activities are mediated by AMPK, a fuel-sensing molecule sharing common targets and cellular activities with SIRT-1. Whether AD preconditioning may involve SIRT-1 activity is not known; however, the protective role of SIRT-1 during ischemia and the potential interplay between AMPK and SIRT-1 suggest this possibility. Methods: Isolated hearts from male Sprague-Dawley rats (n = 85) underwent ischemia/reperfusion (I/R, 30/180 min). Preconditioning with resveratrol (RSV, SIRT-1 activator) was compared to preconditioning with AD alone, or in combination with compound C (CC, AMPK inhibitor) or sirtinol (STN, SIRT-1 inhibitor). For each heart, left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (dLVP), coronary flow (CF) and left ventricular infarct mass (IM) were measured, together with the phosphorylation/activation status of AMPK, LKB1, eNOS and SIRT-1, at the beginning (15 min) and at the end (180 min) of reperfusion. Results and conclusions: When compared to I/R, both RSV and AD improved cardiac function and reduced IM (p < 0.01, p < 0.05, respectively). Cardioprotective effects of AD were completely reversed in the AD+CC group, and significantly attenuated in the AD+STN group. Both RSV and AD increased eNOS, AMPK and LKB1 phosphorylation (for each parameter: p < 0.05 vs. I/R, in both RSV and AD treatment groups) at 15 min of reperfusion, and SIRT-1 activity at the end of reperfusion (p < 0.01, p < 0.05 vs. I/R, respectively). Interestingly, AD-mediated phosphorylation of AMPK and LKB1, and SIRT-1 deacetylation activity was markedly reduced in both the AD+CC and AD+STN groups (p < 0.05 vs. AD). Thus, AD-mediated cardioprotection requires both AMPK and SIRT-1 signaling pathways, that act as a component of a cycle and regulate each other’s activities. [ABSTRACT FROM AUTHOR]

Increased TNFα-mediated JNK signaling in the perivascular adipose tissue (PVAT) may contribute to the pathogenesis of vascular complications in T1DM by reducing adiponectin (Ad) synthesis and therefore impairing Ad-mediated activity in the contiguous blood vessel system. We evaluated whether in vivo treatment with the TNFα blocking antibody infliximab normalized expression of Ad and Ad receptors in various fat depots, and whether this effect correlated with improved endothelial activity and vasodilator function in streptozotocin (STZ)-induced diabetic mice. STZ mice were studied at 1 and 2 weeks after diabetes onset, and compared to age-matched infliximab-treated diabetic (I-STZ) and control animals (CTRL) ( n = 10 each group). In STZ mice, activation of pro-inflammatory JNK signaling was faster in PVAT ( P < 0.01) than in visceral (VAT), epididymal (EAT) and subcutaneous (SAT) adipose depots, and associated with decreased Ad synthesis and dysregulated AdipoR1/R2 levels. In parallel, activation of JNK in aortic endothelial cells and mesenteric arteries was associated with decreased expression/phosphorylation of eNOS and impaired ACh-mediated vasodilation ( P < 0.05 vs. CTRL). Treatment with infliximab abrogated JNK activation, ameliorated Ad protein expression, and normalized expression of both AdipoR1 and AdipoR2 in PVAT, concomitantly improving eNOS expression and vessel relaxation in mesenteric arteries from I-STZ mice ( P < 0.01 vs. STZ). These observations underline the early susceptibility of PVAT to activation of pro-inflammatory JNK signaling, and highlight its potential importance in early vascular changes of T1DM. Further elucidation of the role of PVAT in cardiovascular complications may allow for the design of novel therapeutic strategies directly addressing PVAT pathophysiology. [ABSTRACT FROM AUTHOR]

Study Objective Premenstrual syndrome (PMS) might become severe enough to interfere with normal interpersonal relationships. This study was planned to assess whether administration of vitamin D (200,000 IU at first, followed by 25,000 IU every 2 weeks) for a 4-month period might lessen the appearance and the intensity of mood disorders associated with PMS in young girls with severe hypovitaminosis D. Design, Setting, Participants, Interventions, and Main Outcome Measures One hundred fifty-eight young girls (15-21 years old) with PMS-related severe symptoms of the emotional and cognitive domains and low serum 25-hydroxycholecalciferol (25-OH-D) levels (≤10 ng/mL) were randomly assigned to two treatment groups and treated for 4 months with vitamin D (group 1; n = 80) or placebo (group 2; n = 78). Clinical and hormonal effects were compared between the two groups. Results In patients from group 1, levels of vitamin D reached the normal range (35-60 ng/mL) after the first month and remained stable throughout the whole study. At the end of treatment, anxiety score decreased from 51 to 20 ( P < .001 vs baseline); irritability score declined from 130 to 70 ( P < .001 vs baseline). Crying easily and sadness decreased by a score of 41 and 51 to a score of 30 and 31, respectively ( P < .001). For disturbed relationships, the score decreased from 150 to 70 ( P < .001). Conversely, no appreciable changes were noted in symptom intensity from patients of group 2. The frequency of adverse events (nausea and constipation) was not different between participants of group 1 and group 2. Conclusion On the basis of the present findings, vitamin D therapy can be proposed as a safe, effective, and convenient method for improving the quality of life in young women with severe hypovitaminosis D and concomitant mood disorders associated with PMS. [ABSTRACT FROM AUTHOR]

Background: Vitamin D (Vit D) is important for the regulation of reproductive physiology. In humans, maternal Vit D deficiency has been implicated in several reproductive- and pregnancy-related disorders. Very few data are available regarding the Vit D status in male partners of couples attempting pregnancy. This observational study (IRB Prot. N. 078/13) aimed to evaluate whether low Vit D serum levels in males might decrease the rate of successful conception in couples attempting pregnancy. Methods: Male and female partners of infertile couples (n = 102) were classified into 2 GROUPS according to normal (≡30 ng/ml) or low (below 30 ng/ml) serum Vit D levels in male partners. Semen analysis was performed in each male participant based on the WHO reference criteria. The female partners of both groups were subjected to 3 consecutive cycles of gonadotropin-induced mono-ovulation. The main outcome measures included the clinical pregnancy rate, delivery per patient and per cycle, and miscarriage rate between the 2 groups evaluated at the end of the three-month period of the study. Results: In male partners of both groups, standard semen analysis did not highlight substantial differences in sperm concentration, sperm progressive motility, or typical form. The pregnancy rates per patient and per cycle and delivery rates per patient and per cycle were all significantly higher (p< 0.05) in couples with normal Vit D levels. Conclusions: These results suggest the existence of a relationship between male Vit D serum levels and semen ability to begin a pregnancy during cycles of timed vaginal intercourse. [ABSTRACT FROM AUTHOR]

New and more promising therapies for chronic hepatitis C ( CHC) genotype 1 (G1) naive patients have recently been approved in the United States and Europe, and several more regimens are expected to become available within the next several years. While this scenario unfolds, it is necessary to develop a rational method to allocate current treatment in CHC G1 patients. We performed a cost-effectiveness analysis of boceprevir ( BOC)- and telaprevir ( TVR)-based triple therapy according to different patients' selection strategies. A semi-Markov model of CHC natural history and progression towards end-stage liver disease was built. We considered 3 selection strategies based on METAVIR fibrosis stage: (i) treat all patients with F1-F4 fibrosis, (ii) only F2-F4 and (iii) only F3-F4. For each strategy, TVR interleukin-28B-guided ( IL28B-guided) and BOC rapid virologic response-guided (RVR-guided) therapies were applied. The model assessed the costs and outcomes, using a lifetime and 5-year time horizon, and adopting the Italian National Health System perspective. The incremental cost-effectiveness ratio ( ICER) for F1-F4 strategy relative to F3-F4 was €5132 per quality-adjusted life years gained, across TVR IL-28B-guided therapy, and €7042 in the BOC RVR-guided therapy. Conversely, in the 5-year scenario, the ICER for F1-F4 strategy relative to F3-F4 was €1 818 679 ( TVR IL28B-guided) and €1 866 437 ( BOC RVR-guided) per end-stage liver disease or death ( ESLD-D) avoided. In view of anticipated improvement in the efficacy of future regimens, selective treatment of only patients with advanced fibrosis and cirrhosis with TVR or BOC could represent the most cost-effective strategy to optimize resource utilization. [ABSTRACT FROM AUTHOR]

Abstract: Study Objective: Hirsutism has negative impact on adolescent psychosocial development for both cosmetic and endocrine reasons. This study evaluated the effectiveness of a new intermittent, low-dose finasteride regimen consisting of 2.5 mg of drug given every 3 days (1 day of treatment, 2 days of drug withdrawal) for 6 months in girls with hirsutism by polycystic ovarian syndrome (PCOS) or idiopathic hirsutism (IH). Design and Participants: Twenty-eight girls (15-19 y old) with hirsutism were randomly assigned to 2 treatment groups and treated for 6 months. Fourteen patients (7 with IH, 7 with PCOS) received finasteride; fourteen patients (7 with IH, 7 with PCOS) received placebo. Hirsutism score (HS), clinical, and hormonal effects were compared between the 2 groups. Results: In patients treated with finasteride, the HS value at 6 months was 52.9% lower than that observed at baseline in girls with IH, and 52.8% lower in girls with PCOS (P < .0001 for both). Similarly, the 3α-17 β-androstenediol glucuronide serum levels were decreased by 34.8% in patients with IH, and by 47.5% in patients with PCOS (P < .0001, respectively). Finasteride treatment was well tolerated and did not alter values of BMI, serum levels of sexual hormones, metabolic parameters related to liver and kidney function as well as glycemic and lipidic asset. Conclusions: A low-dose of finasteride, given every 3 days, reduces the HS in young patients affected by PCOS or IH. Compared with conventional continuous finasteride administration, the intermittent low-dose regimen has similar efficacy with the advantage to be safer and less expensive. [Copyright &y& Elsevier]

Failure of intestinal anastomosis is a major complication following abdominal surgery. Biological materials have been introduced as reinforcement of abdominal wall hernia in contaminated setting. An innovative application of biological patch is its use as reinforcement of gastrointestinal anastomosis. The aim of study was to verify whether the bovine pericardium patch improves the healing of anastomosis, when in vivo wrapping the suture line of pig intestinal anastomosis, avoiding leakage in the event of deliberately incomplete suture. Forty-three pigs were randomly divided: Group 1 (control, n = 14): hand-sewn ileo-ileal and colo-colic anastomosis; Group 2 (n = 14): standard anastomosis wrapped by pericardium bovine patch; Group 3 (n = 1) and 4 (n = 14): one suture was deliberately incomplete and also wrapped by patch in the last one. Intraoperative evaluation, histological, biochemical, tensiometric and electrophysiological studies of intestinal specimens were performed at 48 h, 7 and 90 days after. In groups 2 and 4, no leak, stenosis, abscess, peritonitis, mesh displacement or shrinkage were found and adhesion rate decreased compared to control. Biochemical studies showed mitochondrial function improvement in colic wrapped anastomosis. Tensiometric evaluations suggested that the patch preserves the colic contractility similar to the controls. Electrophysiological results demonstrated that the patch also improves the mucosal function restoring almost normal transport properties. Use of pericardium bovine patch as reinforcement of intestinal anastomosis is safe and effective, significantly improving the healing process. Data of prevention of acute peritonitis and leakage in cases of iatrogenic perforation of anastomoses, covered with patch, is unpublished. [ABSTRACT FROM AUTHOR]

Xanthium strumarium L. is a member of the Asteraceae commonly used in Cuba, mainly as diuretic. Some toxic properties of this plant have also been reported and, to date, very little is known about its genotoxic properties. The present work aims was to evaluate the potential cytotoxic and genotoxic risk of whole extract from Xanthium strumarium L. whole extract of aerial parts. No positive response was observed in a battery of four Salmonella typhimurium strains, when exposed to concentrations up to 5mg/plate, with and without mammalian metabolic activation (liver microsomal S9 fraction fromWistar rats). In CHO cells, high concentrations (25-100 μg/mL) revealed significant reduction in cell viability. Results from sister chromatid exchanges, chromosome aberrations, and comet assay showed that X. strumarium extract is genotoxic at the highest concentration used, when clear cytotoxic effects were also observed. On the contrary, no increase in micronuclei frequency in bone marrow cells was observed when the extract was orally administered to mice (100, 500, and 2000mg/Kg doses). The data presented here constitute the most complete study on the genotoxic potential of X. strumarium L. and show that the extract can induce in vitro DNA damage at cytotoxic concentrations. [ABSTRACT FROM AUTHOR]

Granisetron is a 5-HT3 receptors antagonist used in the management of emesis associated with anticancer chemotherapy. It affects intestinal motility with constipating effect. Since the pathway heme oxygenase/carbon monoxide (HO/CO) is involved in gastrointestinal motility, we evaluated the possible interplay between granisetron and agents affecting HO/CO pathways such as zinc protoporphyrin IX (ZnPPIX), an HO inhibitor, or hemin, an HO-1 inducer. ZnPPIX (10 µM) or hemin (10 µM), but not granisetron (0.1, 0.3, 1 µM), affected spontaneous basal activity recorded in rat duodenal strips, in noncholinergic nonadrenergic conditions. Granisetron restored spontaneous basal activity after ZnPPIX, but not after hemin. ZnPPIX decreased and hemin increased the inhibition of activity after electrical field stimulation (EFS), but they did not affect the contraction that follows the relaxation induced by EFS called off contraction. Granisetron did not alter the response to EFS per se but abolished both ZnPPIX and hemin effect when coadministered. In vivo study showed constipating effect of granisetron (25, 50, 75 µg/kg/sc) but no effect of either ZnPPIX (50 µg/kg/i.p.) or hemin (50 µM/kg/i.p.). When coadministered, granisetron effect was abolished by ZnPPIX and increased by hemin. Specimens from rats treated in vivo with hemin (50 µM/kg/i.p.) showed increased HO-1 protein levels. In conclusion, granisetron seems to interact with agents affecting HO/CO pathway both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Background Thiazolidinediones (TZDs) including rosiglitazone (ROSI) are insulin sensitizing agents with beneficial gastrointestinal effects. However, no studies are available on TZDs effect in gastrointestinal motility. We evaluated the effects of ROSI on gastrointestinal inhibitory neurotransmission focusing on the modulatory roles of nitric oxide synthase/nitric oxide (NOS/NO) and heme oxygenase/carbon monoxide (HO/CO) pathways. Methods Spontaneously hypertensive rats (SHR) were used as model of insulin resistance. Duodenal strips were obtained from vehicle-treated SHR, ROSI-treated SHR (5 mg kg−1 by gavage daily per 6 weeks), and Wistar Kyoto (WKY). Inhibitory responses to electrical field stimulation (EFS) were evaluated in the presence of HO inhibitor zinc protoporphyrin IX (ZnPPIX, 10 μmol L−1) or NOS inhibitor NG-nitro- l-arginine (L-NNA, 100 μmol L−1), alone and in combination. Protein levels of HO and NOS isoforms were evaluated by immunohistochemistry and western blot analysis. Key Results Basal responses to EFS were significantly increased in duodenum strips from vehicle-treated SHR vs WKY. This effect was reversed in ROSI-treated SHR. The EFS-mediated relaxation was comparably reduced by ZnPPIX in WKY and SHR, but not in ROSI-treated SHR animals. The L-NNA reduced EFS response to a similar extent in WKY and ROSI -treated SHR, but its effect was significantly higher in vehicle-treated SHR. Expression of HO-1 protein was significantly lower, whereas HO-2 protein levels were unchanged in ROSI-treated SHR with respect to vehicle-treated SHR. Finally, increased levels of nNOS in vehicle-treated SHR were reduced in ROSI-treated SHR. Conclusions & Inferences Chronic ROSI treatment reverses increased SHR duodenal inhibitory response acting on CO and NO components. [ABSTRACT FROM AUTHOR]

Alterations in gastrointestinal motility of diabetic patients have been linked to degenerative changes induced by glucose abnormalities in the peripheral nervous system. The heme oxygenase/carbon monoxide (HO/CO) signalling represents one of the non-adrenergic/non-cholinergic (NANC) neurotransmission pathways involved in regulation of physiological peristalsis. To investigate the role of HO/CO system in intestinal motility under diabetic conditions, the response to electrical field stimulation (EFS) and western blot analysis of HO/CO pathway components were studied on duodenum longitudinal smooth muscle strips isolated from streptozotocin (STZ)-treated diabetic rats (65 mg kg−1, i.p.) and respective controls (CTRL), 6 weeks after the onset of diabetes. When compared to CTRL, the ability of CO releasing molecule (CORM-3) (100–400 μmol L−1) to enhance NANC relaxation was significantly impaired in STZ-treated rats ( P < 0.05). Conversely, in vitro incubation with the HO inhibitor ZnPPIX (10 μmol L−1, 60 min) significantly reduced EFS-induced relaxation in CTRL ( P < 0.05), but not in STZ-treated rats. Interestingly, the ability of ZnPPIX to inhibit EFS-induced relaxation was partially restored in STZ-treated rats co-administered in vivo with the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) (0.5 mg per 100 g body weight weekly). Expression of inducible HO-1 protein was increased in homogenates from STZ-treated rats ( vs CTRL, P < 0.01), and further increased in STZ-treated rats receiving CoPPIX ( P < 0.05). Taken together, our data underline the essential role of HO/CO system in regulation of inhibitory NANC neurotransmission in the duodenum and suggest that dysregulation of HO/CO activity may represent one mechanism by which gastrointestinal motility is altered in diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Punica granatum L. (Punicaceae) whole fruit extracts, have been used in Cuban traditional medicine as an effective drug for the treatment of respiratory diseases. This species showed interesting anti-viral activity, e.g. aqueous or hydroalcoholic extracts of whole fruits have proved highly active against the influenza virus. However, some toxic properties of this extract have also been reported and, to date, very little is known about its genotoxic properties. In the present study, the genotoxicity of a Punica granatum (pomegranate) whole fruit extract was assessed using different in vitro and in vivo assays that detect DNA damage at different expression levels. Results from reversion and gene-conversion test in microorganisms, sister chromatid exchanges, micronuclei and sperm-shape abnormality assays in mice, clearly showed that the hydroalcoholic extract of P. granatum whole fruits is genotoxic when tested both in vitro and in vivo. [Copyright &y& Elsevier]

Objective: To evaluate the hypothesis that pretreatment with estrogens in women affected by premature ovarian failure (POF) may improve the results of ovarian stimulation. Design: Double-blind, randomized, placebo-controlled study. Setting: Outpatient department in an academic research environment. Patient(s): Fifty women with POF seeking pregnancy. Intervention(s): Before starting ovarian stimulation, group 1 received 0.05 mg ethinyl-E2 (EE) three times a day for 2 weeks, while group 2 received placebo. Ovarian stimulation was carried out with recombinant FSH (r-βFSH), 200 IU/day/SC. Both EE and placebo were administered during ovarian stimulation. Human chorionic gonadotropin (10,000 IU/IM) was added when the follicle exceeded a mean diameter of 18 mm. Main Outcome Measure: Rate of ovulation in women with POF. Result(s): Levels of FSH before stimulation were significantly lower in group 1 than in group 2. The rate of ovulation in group 1 (8/25; 32%) was significantly higher than in group 2 (0/25; 0%). Notably, induction of ovulation was successful only in patients whose FSH levels after EE treatment were ≤15 mIU/mL. Conclusion(s): Our data suggest that pretreatment with EE improves the success of rate of ovulation induction with exogenous gonadotropins in patients with POF. A threshold of FSH ≤15 mIU/mL should be achieved before starting ovarian stimulation. [Copyright &y& Elsevier]

In a prospective randomized study 38 women with idiopathic hirsutism or polycystic ovary syndrome (PCOS) received 2.5 mg of finasteride every day or every 3 days. Intermittent low-dose administration of finasteride was as effective as continuous administration in reducing hirsutism score and was accompanied by a lower incidence of side effects. [Copyright &y& Elsevier]

1 Prolonged bed rest or exposure to microgravity may cause several alterations in autonomic nervous system response (ANSR).2 Hindlimb unloading (HU) rats were used as an animal model of simulated microgravity to investigate ANSR changes. The experiments were carried out to investigate the effects of simulated microgravity on the autonomic nervous response of the perfused mesenteric vascular bed (MVB), vas deferens and the colon and duodenum from 2-week HU rats.3 In MVB preparations of HU rats, the frequency-dependent increases in perfusion pressure with perivascular nerve stimulation (PNS; 8–40 Hz) were inhibited, whereas the noradrenaline (NA) concentration-dependent (1–100 μm) perfusion pressure increases were potentiated. The latter most probably reflected up-regulation ofα-adrenergic receptor function. Relaxant responses of NA-precontracted MVB to PNS (4–30 Hz) or isoprenaline were not different between control and HU preparations, while vasodilation induced by the endothelial agonist ACh was reduced.4 Transmural stimulation (2–40 Hz) induced frequency-dependent twitches of the vas deferens which were reduced in vas deferens of HU rats, while the sensitivity to NA-induced contraction was significantly increased.5 In the gastroenteric system of HU rat, direct contractile responses to carbachol or tachykinin as well as relaxant or contractile responses to nervous stimulation appeared unchanged both in the proximal colon rings and in duodenal longitudinal strips.6 In conclusion, HU treatment affects peripheral tissues in which the main contractile mediators are the adrenergic ones such as resistance vessels and vas deferens, probably by reducing the release of neuromediator. This study validates NA signalling impairment as a widespread process in microgravity, which may most dramatically result in the clinical phenotype of orthostatic intolerance. [ABSTRACT FROM AUTHOR]

Phyllanthus orbicularis HBK is an endemic Cuban plant whose aqueous extract has been proposed as an effective drug for the treatment of viral diseases. In addition, antimutagenic properties of this extract have also been reported. In the present study, the genotoxicity of this plant extract was assessed using different in vitro and in vivo assays. Results from SOS gene induction, gene reversion and conversion, and SMART assays clearly show that P. orbicularis aqueous extract does not induce either primary DNA damage or mutation. Additionally, no statistically significant difference was found in the percentage of chromosomal aberrations in Chinese hamster ovarian (CHO) cells treated with the plant extract. On the contrary, micronuclei and abnormal anaphase were induced by this extract in CHO cells. This genotoxic effect was related to a high cytotoxicity. Single spots were detected in the SMART assay. These results point to a possible aneugenic effect of the P. orbicularis aqueous extract at cytotoxic doses which are much higher than those seen by their antiviral and antimutagenic activities. [Copyright &y& Elsevier]

Summary 1 The present study aimed to evaluate the role of κ-opioid receptors at two peripheral sites, the vas deferens and the proximal colon, in κ-opioid receptor knockout mice. We investigated the role of the κ-opioid receptor in the vas deferens twitch response and in the colonic ‘off-contraction’, a rebound contractile response which follows the inhibitory response to low frequencies stimulation (10, 20, 30 Hz) and which has been suggested to ‘locally’ reproduce the contractile component of the peristaltic reflex. 2 Transmural stimulation of the vas deferens at lower frequencies (10 Hz, 10 V, 1 ms pulse trains lasting 0.5 s) evoked a contractile response that was significantly higher in the preparations from knockout mice because of lack of κ-opioid receptors than in wild type mice. A selective κ-opioid receptor agonist, U-50,488H, induced a dose-dependent inhibition of the electrically stimulated contraction in vas deferens. The percentages of reduction of the twitch response were significantly lower in knockout mice than in wild type mice after treatment with U-50,488H. The reduction of twitch response caused by U-50,488H was not reversed by administration of nor-binaltorphimine (nor-BNI) (5 × 10[sup -6] m), a selective κ-opioid receptor antagonist, in preparations from both knockout mice and wild type mice. U-50,488H has no effect on postsynaptic adrenergic receptors, as its administration did not affect the direct contractile response to noradrenaline. 3 Transmural stimulation (5 Hz, 20 V, 2 ms pulse trains lasting 30 s) induced inhibition of spontaneous activity of colonic strips during the period of stimulation, followed by an ‘off-contraction’ after the cessation of stimulation. The statistical evaluation of the ‘off-contraction’ responses between the two strains showed no significant difference. The off-contraction, measured in specimens from knockout mice, was inhibited concentration-dependently by U-50,488H (P < 0.01) and significantly less than from wild type mice. 4 The effect of U-50,488H was not reversed by administration of nor-BNI (5 × 10[sup -6] m), either in preparations from knockout mice or from wild type mice. 5 Our data may suggest that κ-opioid receptors are involved in some peripheral responses to the nerve stimulation, as indicated by the effect of U-50,488H, a selective κ-opioid receptor agonist. However, the involvement of κ-opioid receptor was also present, although less apparent, in κ -opioid receptor knockout mice, suggesting either that this drug acts not only on κ-opioid receptors but also on other receptor sites, such as κ-like receptors. An alternative interpretation can be related to a sodium channel blocking action of U-50,488H, which could explain the inhibitory effects of twitch response still present but less evident in knockout strain and the lack of effect of the antagonist nor-BNI. [ABSTRACT FROM AUTHOR]

Background Tachykinins (TKs) have been shown to be involved in the excitatory enteric motor pathway. This study aimed to examine the direct and nerve-mediated effect of specific NK[sub 1], NK[sub 2] and NK[sub 3] receptor agonists and antagonists in colonic preparations from control subjects and patients with idiopathic chronic constipation (ICC). Materials and methods Cumulative concentrations of Sar[sup 9]Met(O[sub 2])[sup 11] substance P (selective NK[sub 1] receptor agonist), [Ala[sup 5],b-Ala[sup 8]]-neurokinin A (4-10) (selective NK[sub 2] receptor agonist) and [MePhe[sup 7]]-neurokinin B (selective NK[sub 3] receptor agonist) were tested on colonic circular muscle strips to evaluate the direct drug effects. In addition, in the presence of atropine, the role of TKs in the off-contraction that follows the typical inhibitory response evoked by low frequencies of electrical field stimulation (0·5-10 Hz, 20 V, 1 ms pulse trains lasting 1 min) was investigated. Results In control preparations, the rank order of potency was: NK[sub 2] receptor-selective agonist > NK[sub 3] receptor-selective agonist > NK[sub 1] receptor-selective agonist. The off-contraction was found to be reduced by about 30-40% in colonic circular muscle from ICC patients with respect to controls. Incubation with the NK[sub 1] receptor agonist did not modify the off-contraction measurements in either control or ICC preparations. Conversely, both NK[sub 2] and NK[sub 3] receptor agonists significantly (P < 0·01) increased the off-contraction in ICC preparations only. This increased response was fully antagonized by MEN-10627, a NK[sub 2] and NK[sub 3] receptor antagonist depending on the dose. Conclusions We may conclude that ICC is hyporesponsive to TKs and that the contractile reflex to distension is greatly reduced in ICC disease, but can be restored by incubation with NK[sub 2] and NK[sub 3] receptor agonists. [ABSTRACT FROM AUTHOR]

BackgroundErythromycin has been shown to have profound prokinetic effects on the gastrointestinal tract of humans and animals, probably through its action on endogenous motilin receptors. The purpose of this study was to determine both the direct and indirect effects (‘off contraction’) of erythromycin and motilin on ex vivo circular muscle strips of the distal colon from patients with or without idiopathic chronic constipation (ICC). Materials and methodsCumulative concentrations of erythromycin (1–20 μM) and motilin (0.05–1 μM) were tested in both control and ICC preparations in order to evaluate the direct drugs effect. A range doses of both erythromycin (0.5–10 μM) and motilin (0.05–0.5 μM) were tested on their ability to affect the off-contraction that follows the typical inhibitory response evoked by low frequencies of Electrical Field Stimulation (EFS) (1–5 Hz, 20 V, 1 msec pulse trains lasting 1 min). ResultsThe direct effect of both erythromycin and motilin was a slight increase (less than 10% of the maximal ACh-induced contraction) in the basal tension, with no dose–response relationship. The off-contraction, evoked by EFS, was not affected by drugs pretreament in control preparations. Conversely, in ICC preparations both drugs significantly increased the off-contraction (about 30%). ConclusionsErythromycin causes mainly an indirect contractile effect in circular muscle strips from ICC patients. This effect may be related to the activation of inhibitory neuronal motilin receptors. This activation might potentiate NANC relaxation, proportionally increasing the circumferential reflex contraction that follows the EFS-induced relaxation. [ABSTRACT FROM AUTHOR]

So-called apraxia of eyelid opening (scAEO) has been described chiefly in the context of extrapyramidal disorders. We described 10 new patients with scAEO developing in the absence of any other CNS sign and reviewed the 11 cases with isolated scAEO reported in the literature. Combining our patients and those from the literature, peak age at onset was in the 6th decade and there was a female preponderance of 2:1. The characteristic inability to initiate lid elevation was frequently associated with failure to sustain lid elevation, thus suggesting that eyelid motor control may be abnormal in isolated scAEO. Antecedent events included ocular signs and symptoms consistent with diseases of eyes or face (4 cases in our series and 2 in the literature), chronic treatment with flunarizine (1 case), and family history of dystonia (1 case). Flunarizine discontinuation led to sustained remission of the eyelid disturbance. Overall, these clues suggest the involvement of the extrapyramidal system in the pathophysiology of isolated scAEO. Familial clustering of isolated scAEO in one of our patients may be in favor of a genetic contribution. In our series, botulinum toxin administration close to the pretarsal part of the orbicularis oculi muscle significantly improved scAEO in 8/10 cases, whereas orbital/preseptal injection had no effect. We conclude that the term ‘apraxia’ may not be the correct descriptive term even when the eyelid disturbance occurs without any other CNS disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether the addition of finasteride (a 5〈-reductase inhibitor) to conventional protocol of ovarian stimulation with gonadotropin can improve ovarian follicular growth in polycystic ovary syndrome (PCOS) women who did not respond to previous stimulation with gonadotropin alone. Design: Double-blind randomized study. Setting: Outpatient in an academic research environment. Patient(s): Thirty-six PCOS patients in whom the previous multifollicular stimulation protocols with gonadotropin failed. Intervention(s): The patients were randomly assigned to two treatment groups: group 1 underwent ovarian stimulation with recombinant FSH (rFSH) plus finasteride, and group 2 received rFSH alone. When the dominant follicle reached a mean diameter of 18 mm, hCG was administered and finasteride withdrawn. Main Outcome Measure(s): Ovulation rate in women with PCOS. Result(s): Follicular growth and ovulation occurred in eight patients in group 1, whereas no cases were detected in group 2. Conclusion(s): This study confirms that hyperandrogenism interferes with follicular growth and suggests that administration of finasteride during ovarian stimulation with rFSH improves ovulation rate in selected hyperandrogenic anovulatory women. [Copyright &y& Elsevier]

We explored the significance of the L-Arginine/asymmetric dimethylarginine (L-Arg/ADMA) ratio as a biomarker of endothelial dysfunction in stroke patients. To this aim, we evaluated the correlation, in terms of severity, between the degree of endothelial dysfunction (by L-Arg/ADMA ratio), the methylene tetrahydrofolate reductase (MTHFR) genotype, and the interatrial septum (IAS) phenotype in subject with a history of stroke. Methods and Results: L-Arg, ADMA, and MTHFR genotypes were evaluated; the IAS phenotype was assessed by transesophageal echocardiography. Patients were grouped according to the severity of IAS defects and the residual enzymatic activity of MTHFR-mutated variants, and values of L-Arg/ADMA ratio were measured in each subgroup. Of 57 patients, 10 had a septum integrum (SI), 38 a patent foramen ovale (PFO), and 9 an ostium secundum (OS). The L-Arg/ADMA ratio differed across septum phenotypes (p ≤ 0.01), and was higher in SI than in PFO or OS patients (p ≤ 0.05, p ≤ 0.01, respectively). In the PFO subgroup a negative correlation was found between the L-Arg/ADMA ratio and PFO tunnel length/height ratio (p ≤ 0.05; r = − 0.37; R2 = 0.14). Interestingly, the L-Arg/ADMA ratio varied across MTHFR genotypes (p ≤ 0.0001) and was lower in subgroups carrying the most impaired enzyme with respect to patients carrying the conservative MTHFR (p ≤ 0.0001, p ≤ 0.05, respectively). Consistently, OS patients carried the most dysfunctional MTHFR genotypes, whereas SI patients the least ones. Conclusions: A low L-Arg/ADMA ratio correlates with impaired activity of MTHFR and with the jeopardized IAS phenotype along a severity spectrum encompassing OS, PFO with long/tight tunnel, PFO with short/large tunnel, and SI. This infers that genetic MTHFR defects may underlie endothelial dysfunction-related IAS abnormalities, and predispose to a cryptogenic stroke. Our findings emphasize the role of the L-Arg/ADMA ratio as a reliable marker of stroke susceptibility in carriers of IAS abnormalities, and suggest its potential use both as a diagnostic tool and as a decision aid for therapy. [ABSTRACT FROM AUTHOR]

Presents a correction to an article published in the July 2001 issue of the `European Journal of Clinical Investigation,' which focused on idiopathic chronic constipation.