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C Guerrera,F Colivicchi,R Pola,F Travaglino,G Filice,G Guerrera,D Melina Malignant hypertension causes anatomical and functional damage in several target organs, in particular brain, retina, heart and kidneys. Although vascular lesions in the gastroenteric tract are known to occur in several instances, their clinical relevance is unknown. In this study five cases of mal... ( view more )ignant hypertension, presenting with acute abdominal symptoms, are reported. A history of essential arterial hypertension was present in three patients; while one patient had a previous diagnosis of renovascular hypertension and one patient had renoparenchymal hypertension. However, in all cases the antihypertensive treatment was discontinued and inadequate before the accelerated malignant phase. The acute abdominal symptoms at presentation were due to intestinal infarction in 3 patients and acute pancreatitis in 2 patients. One patient with intestinal infarction died of postoperative cardiogenic shock. Our data are in agreement with previous reports describing the possible intra-abdominal complications of malignant hypertension. The therapeutic approach in such conditions should always consider an effective antihypertensive treatment in conjunction with surgical options. ( view less ) F Colivicchi,C Guerrera,E Bevilacqua,E Guerrera,D MelinaIschemic hepatitis represents a condition in which an acute circulatory failure determines a striking elevation of both serum transaminases and total bilirubin and a prolongation of prothrombin time. Such impairment of liver function tests is due to a haemodynamic hepatocyte injury, showing focal c... ( view more )entrilobular necrosis as the specific pathologic correlate. In this paper the authors describe four different cases of ischemic hepatitis, in which an acute derangement of liver function tests occurred as a consequence either of myocardial failure or of systemic venous congestion. Finally, the authors review all current international literature concerning the various clinical, pathologic and therapeutic features of ischemic hepatitis. ( view less ) D Melina,G Guerrera,G Melina,C Guerrera The above study was undertaken in order to evaluate the efficacy and tolerability of low dose calcium heparin for postinfarct ischemic heart disease (CIPI). In particular, the incidence was checked of: cardiovascular death, reinfarction, angina pectoris, TIA or RIND, stroke, arterial thromboembolis... ( view more )m, venous thromboses, heart failure, complex ventricular arrhythmias, silent myocardial ischemia. Eighty patients with CIPI were divided into two groups similar for age, sex, physical features, cardiovascular risk factors, site of infarction, length of hospitalization, complications during hospitalization, clinical and instrumental findings at discharge, concomitant pathology. Upon discharge, patients were randomized into group 1 for traditional treatment and group 2 which in addition received 12,000 U calcium heparin s.c. every 24 h. After 12 months, during which patients were submitted to periodical laboratory and instrumental (standard and dynamic ECG, echoG) evaluation, group 2 had significantly fewer cardiovascular events than group 1 both as to overall number of events and as to number of events per individual patient. Especially, silent myocardial ischemia and ventricular arrhythmias were less frequent in group 2 patients and these two events, especially if coincident, are known to have severe prognostic implications. The efficacy of low-dose calcium heparin must be attributed to the enhancement of physiological antithrombotic mechanisms with compensation of blood clotting disorders that are fairly frequent in CIPI patients. Long-term s.c. administration was well tolerated. ( view less ) D Melina,F Colivicchi,G Guerrera,G Melina,A Frustaci,M Caldarulo,C Guerrera Seventy-eight men with borderline hypertension according to the World Health Organization criteria underwent echocardiographic examination, followed by simultaneous ambulatory blood pressure and electrocardiographic monitorings for 24 h. The prevalence of echocardiographic left ventricular hypertro... ( view more )phy was 16.6% (13/78). Borderline hypertensives with left ventricular hypertrophy had more supraventricular (P less than .001) and ventricular ectopic beats (P less than .001) than normotensive controls and borderline hypertensives without cardiac involvement. Furthermore, ventricular ectopic activity was significantly related to left ventricular mass (r = 0.58, P less than .05) in borderline hypertensives showing echocardiographic evidence of left ventricular hypertrophy. Our findings suggest that noninvasive assessment of target organ status, including echocardiography, should be employed to optimize risk stratification in borderline hypertension. ( view less ) D Melina,G Guerrera,A Santoliquido,C Guerrera,V Musumeci,G Nicolò,R CataldoThe antihypertensive efficacy of combination therapy with N-E-A was evaluated during 6 months in 15 patients with hypertension associated with mild to moderate kidney failure. After 6 months a significant reduction of SBP and DBP (p < 0.001), with improvement of creatinine clearance and with no adv... ( view more )erse effects on ECG, heart rate and routine laboratory tests test, was observed in 3 patients treated with N 20 mg x 2/d + E 10 mg/d + A 50 mg/d and in 8 patients treated with N 20 mg x 3 + E 10 mg x 2, + A 50 mg x 2. Four patients did not respond to this therapy. ( view less ) G Guerrera,D Melina,C Felici,C Guerrera,A Santoliquido,V Musumeci The aim of the study was to analyse electrocardiographic alterations in 30 patients with slight to moderate essential arterial hypertension during the course of hypertensive attacks (DAP greater than 115 mmHg). Standard hematochemical tests were performed in basal conditions, together with 24-h ECG... ( view more ) monitoring and an echocardiogram to measure the left ventricular mass index. Echographic monitoring was carried out during hypertensive attacks and for 2 h after the return to basal pressure values. In basal conditions patients showed slight hypopotassemia (23%), left ventricular echographic involvement (57%), left ventricular hypertrophy with or without systolic strain (43%), and ventricular extrasystole (VE) classified as Lown's 1st and 2nd class (17%). During the course of hypertensive attacks, there was a significant increase in systolic strain, the appearance of anterolateral subendocardial ischemia (10%), left anterior hemiblock (3%), lateral subepicardial ischemia (3%), and a marked increase in VE (67%) which were complex in 40% of cases (Lown's classes 3, 4 and 5). A significant correlation was found between the left ventricular mass index and VE/h. The authors stress the multifactorial pathogenesis of echographic alterations and underline left ventricular involvement, acute hemodynamic strain and consequent alterations of coronary perfusion, hypopotassemia, and increased levels of circulating catecholamines. ( view less ) G Guerrera,D Melina,F Colivicchi,A Santoliquido,G Guerrera,G FolliTwenty-eight men with borderline hypertension according to the World Health Organization criteria underwent maximal exercise testing, and then were followed for a two year period. The prevalence of abnormal blood pressure behavior during exercise was 53.58% (n = 15). During follow-up established hy... ( view more )pertension developed in 63.33% (n = 10) of subjects with an abnormal blood pressure response to exercise, and only in 15% (n = 2) of subjects with normal blood pressure behavior. In predicting established hypertension development in a two year follow-up, maximal exercise testing has the following statistical values: sensitivity = 83.33%, specificity = 68.75%, accuracy = 75%, positive predictive value = 66.66%, negative predictive value = 84.61%. ( view less ) G Guerrera,D Melina,C Felici,F Colivicchi,A Santoliquido,C Guerrera,V Musumeci,G Folli Aim of this study was to assess blood pressure (BP) response to exercise in borderline hypertensive subjects and to evaluate its predictive value for subsequent established hypertension development: 74 male subjects (28 borderline subjects, 26 normotensive subjects and 20 subjects with established ... ( view more )hypertension) underwent a maximal exercise testing in the sitting position with a bicycle ergometer at the beginning of the study and then after 1 and 2 years; besides casual BP was controlled every 3 months for 2 years. Systolic BP exceeding 220 and/or diastolic BP exceeding 105 mmHg at maximal exercise and/or diastolic BP exceeding 100 mmHg at th fifth min of recovery were considered as abnormal. On the basis of BP response to exercise we divided our study group in: normotensive subjects with a normal BP response (Group A: 88%); normotensive subjects with an abnormal BP response (Group B: 12%); borderline subjects with a normal BP response (Group C: 46%); borderline subjects with an abnormal BP response (Group D:56%). At the end of a 2-year follow-up established hypertension developed in 1 subject of Group B (33%), in 2 subjects of Group C (15%) and in 10 subjects of Group D (67%); 7 subjects of Group C returned to normotension (54%). The incidence of established hypertension is significantly higher in borderline subjects with an abnormal BP response to exercise. This finding is probably due to both functional and organic factors and stresses the predictive value of exercise testing in borderline hypertension. ( view less ) M A Satta,A Scoppola,D Melina,G Guerrera,L Capaldi,G Guerrera,G Folli Data in the literature suggest that cases of hypoalphalipoproteinemia involve an increase in thromboxane B2 (TXB2) together with an increased risk of atherosclerosis. A recent detailed examination of a 32-year-old man revealed clinical and biochemical features strongly indicative of that pathology.... ( view more ) The case presented several unusual features: marked infiltration of the skin and mesenteric lymph nodes by histiocytic lipids with sufficient hyperplasia to induce acute intestinal occlusion combined with an in vivo TXB2 generation curve, subsequently inhibited by aspirin, that was comparable to the curves of the control subjects. Furthermore there were no signs of early atherosclerotic damage so that it was possible to postulate the hypothesis that despite the 50% drop in alpha-lipoprotein levels, they were still sufficient to ensure normal turnover of the other lipoproteins so that, however complex the clinical condition, it was an incomplete expression of a phenotype. ( view less ) G Guerrera,D Melina,L Capaldi,C Tatulli,C Cardillo,G Guerrera,R Mauro,V Musumeci,L Savi,G Folli The aim of this study, whose preliminary findings are reported, is to evaluate the efficacy of captopril, administered by a sublingual route, in the treatment of hypertensive emergencies. Captopril has been given by this route to 20 hypertensive patients while these had an ongoing hypertensive cris... ( view more )is (defined as a systolic arterial pressure above 200 mmHg associated with a diastolic arterial pressure above 115 mmHg). Arterial pressure has been measured after 5, 20, 10, 15, 30, 45, 60 and 120 min. For 8 patients it has been measured until the eighth hour. Results were the following: a satisfactory control of hypertensive crisis in 85% of patients, as stated by a slight but significant drop of arterial pressure after 10 min (15/10 mmHg; p less than 0.05) and by a maximum antihypertensive effect after 30 min (57/39 mmHg; p less than 0.001); an antihypertensive effect was evident until 6 hours after the administration of the drug; a positive correlation between the antihypertensive effect and pretreatment levels of arterial pressure and plasma renin activity; drug was free from relevant side effects; sublingual captopril can be considered an efficacious, easy to use and valuable tool in the treatment of hypertensive emergencies. ( view less ) D Melina,G Guerrera,A Santoliquido,F Colivicchi,G Melina,V Musumeci,C Guerrera The above study was intended to assess the efficacy of nicardipine in mild to moderate essential arterial hypertension and to check whether there are medium term changes in kidney function and urinary excretion of electrolytes in the course of nicardipine treatment. Twenty patients with mild to mod... ( view more )erate essential arterial hypertension were treated daily with 40-80 mg doses of slow-release nicardipine after a wash-out period. Systolic and diastolic blood pressure was measured with traditional sphygmomanometer on entry and after 4, 8, and 12 weeks' treatment. Also, on entry and at conclusion of the study, the following parameters were measured: plasma renin activity, creatinine clearance, 24-hour urinary excretion of Na, K, Ca, and aldosterone. Nicardipine treatment was well tolerated and no significant changes of heart rate, creatinine clearance and urinary excretion of Na, K, Ca and aldosterone were observed after 12 weeks' treatment. The efficacy of nicardipine for the management of mild to moderate hypertension was thus confirmed. The absence of a natriuretic effect after 12 weeks' treatment goes to show that any diuretic action of the drug is irrelevant to its therapeutic effect which appears to be due mainly to its vasodilatory action. ( view less ) G Guerrera,D Melina,L Capaldi,R Mauro,F Colivicchi,C Cardillo,G Guerrera,V Musumeci,L Savi,A Santoliquido Aim of the study was to assess the effectiveness and tolerability of sublingual captopril (SLC) versus sublingual nifedipine (SLN) in treating hypertensive emergencies. During hypertensive crises (systolic blood pressure exceeding 200 mmHg and diastolic blood pressure exceeding 115 mmHg) forty hype... ( view more )rtensive patients received either 25 mg of SLC or 10 mg of SLN in a randomized single blind fashion. Blood pressure and heart rate were then controlled after 5, 10, 15, 20, 30, 45, 60, 120 min. and, in 18 cases, up to the 8th hour from the administration. Our results showed: 1) a satisfactory control of the hypertensive crises in 80% of patients treated with SLC with a significant blood pressure reduction after 10 min. (13/8 mmHg, p less than 0.02), while the maximum hypotensive effect was achieved after 30 min. (52/36 mmHg, p less than 0.001); SLN was able to reduce blood pressure in 90% of all the cases, with a significant reduction after 5 min. (15/11 mmHg, p less than 0.02) and hypotensive peak after 20 min (57/38 mmHg, p greater than 0.001); 2) no significant differences for hypotensive effectiveness between the two groups, but with SLC having a mildly delayed onset of action when compared to SLN; 3) antihypertensive effect lasting for about 6 hours in patients treated with SLC and blood pressure progressively raising after 4 hours in patients who received SLN; 4) a significant correlation between blood pressure reduction and blood pressure before drug administration in both groups; a significant correlation between pretreatment PRA and antihypertensive effect in the SLC group. We conclude that both drugs are effective and useful in treating hypertensive emergencies. Anyway we think that in severe forms SLN should be preferred for the shorter time preceding onset of action. ( view less ) A Germanà,F Marino,M C Guerrera,S Campo,P de Girolamo,G Montalbano,G P Germanà,F J Ochoa-Erena,E Ciriaco,J A Vega S100 proteins are EF-hand calcium-binding protein highly preserved during evolution present in both neuronal and non-neuronal tissues of the higher vertebrates. Data about the expression of S100 protein in fishes are scarce, and no data are available on zebrafish, a common model used in biology to ... ( view more )study development but also human diseases. In this study, we have investigated the expression of S100 protein in the central nervous system of adult zebrafish using PCR, Western blot, and immunohistochemistry. The central nervous system of the adult zebrafish express S100 protein mRNA, and contain a protein of approximately 10 kDa identified as S100 protein. S100 protein immunoreactivity was detected widespread distributed in the central nervous system, labeling the cytoplasm of both neuronal and non-neuronal cells. In fact, S100 protein immunoreactivity was primarily found in glial and ependymal cells, whereas the only neurons displaying S100 immunoreactivity were the Purkinje's neurons of the cerebellar cortex and those forming the deep cerebellar nuclei. Outside the central nervous system, S100 protein immunoreactivity was observed in a subpopulation of sensory and sympathetic neurons, and it was absent from the enteric nervous system. The functional role of S100 protein in both neurons and non-neuronal cells of the zebrafish central nervous system remains to be elucidated, but present results might serve as baseline for future experimental studies using this teleost as a model. ( view less ) Valeria Pittalà,Maria Modica,Loredana Salerno,Maria Angela Siracusa,Francesco Guerrera,Ilario Mereghetti,Alfredo Cagnotto,Tiziana Mennini,Giuseppe Romeo The 21-amino acid peptide endothelin-1 (ET-1) is the predominant isoform of the endothelin peptide family, which includes ET-2, and ET-3. These peptides display a variety of physiological activities including vasoconstriction and the stimulation of cell proliferation in tissues both within and outs... ( view more )ide of the cardiovascular system. They exert their actions via activation of two distinct receptor subtypes, ET(A) and ET(B), belonging to the G protein-coupled receptor (GPCR) superfamily. Ligands of these receptors have received numerous citations in the recent pharmaceutical literature. In particular receptor antagonists, both ET(A)- and ET(B)-selective, as well as non-selective, have been described due to their wide therapeutic potential. As a part of our program toward the development of selective ET(A) ligands we have designed and we now report new molecules based on 2-substituted-4-aryl-3-quinolinecarboxylic acid moiety. Binding profile for some compounds (40, 44, 46, and 47) of this class showed a reasonable affinity and selectivity for ET(A) receptors. ( view less ) L Salerno,F Guerrera,M Modica,G Romeo,V Pittalà,M A Siracusa,I Mereghetti,A Cagnotto,T MenniniIn the present study we describe the synthesis of a new series of 1,2,4-triazoles: [3-(arylmethyl)thio-5-aryl-4H-[1,2,4]triazol-4-yl]acetic acids 5a-g, [5-(arylmethyl)thio-3-aryl-1H-[1,2,4]triazol-1-yl]acetic acids 8a-d, and [3-(aryl-methyl)thio-5-aryl-1H-[1,2,4]triazol-1-yl] acetic acids 9a-d. The... ( view more )se compounds were tested in binding assays to evaluate their ability as ligands for human ET(A) and ET(B) receptors stably expressed in CHO cells; some of the tested compounds showed affinity in the micromolar range. ( view less ) Ida Chiara Guerrera,Nicholas H Keep,Jasminka Godovac-Zimmermann Following stimulation of NRK49F rat kidney fibroblast cells with epidermal growth factor, possible preemptive cross-talk between arginine methylation and serine and tyrosine phosphorylation was observed for Rho guanidine nucleotide dissociation inhibitor 1 (RhoGDI-1). Five dimethylation sites (Lys5... ( view more )0, Lys52, Arg111, Arg152, Arg180) and two new phosphorylation sites (Tyr144, Ser148) were identified for RhoGDI-1. All presently known phosphorylation sites for RhoGDI-1 lie within the 10 residues immediately prior to the 3 sites for arginine dimethylation, and these dimethylation/phosphorylation modules may constitute functional switches. Consideration of structural data and other literature for RhoGDI-1 suggests that methylation and phosphorylation cooperatively affect formation of complexes with different Rho/Rac family proteins and that methylation may be crucial in partitioning of RhoGDI-1 between different functional roles. On the basis of results presented here, it can be implied that unidentified arginine methyltransferases may exist and that arginine methylation may have a greater role in cellular signaling processes than is currently recognized. The combined use of SILAC labeling of arginine (SILAC = stable isotope labeling by amino acids in cell culture), immobilized metal affinity chromatography based phosphoprotein enrichment, and mass spectrometry is clearly a useful method for this investigation. ( view less ) Noura Bensalem,Sandrine Masscheleyn,Julien Mozo,Benoit Vallée,Franck Brouillard,Stéphanie Trudel,Daniel Ricquier,Aleksander Edelman,Ida Chiara Guerrera,Bruno Miroux Membrane proteins play a large variety of functions in life and represent 30% of all genomes sequenced. Due to their hydrophobic nature, they are tightly bound to their biological membrane, and detergents are always required to extract and isolate them before identification by mass spectrometry (MS... ( view more )). The latter, however remains difficult. Peptide mass fingerprinting methods using techniques such as MALDI-TOF MS, for example, have become an important analytical tool in the identification of proteins. However, PMF of membrane proteins is a real challenge for at least three reasons. First, membrane proteins are naturally present at low levels; second, most of the detergents strongly inhibit proteases and have deleterious effects on MALDI spectra; and third, despite the presence of detergent, membrane proteins are unstable and often aggregate. We took the mitochondrial uncoupling protein 1 (UCP1) as a model and showed that differential acetonitrile extraction of tryptic peptides combined with the use of polystirene Bio-Beads triggered high resolution of the MALDI-TOF identification of mitochondrial membrane proteins solubilized either with Triton-X100 or CHAPS detergents. ( view less ) L J Nannini,G A Zaietta,A J Guerrera,J A Varela,O M Fernández,D M Flores RATIONALE: Identification of asthmatic subjects with low perception of dyspnea (POD) that are at higher risk of hospitalization, near-fatal and fatal asthma could improve their management. OBJECTIVE: Create a simple procedure that facilitate the recognition of low POD. METHODS: We enrolled near fat... ( view more )al asthma (NFA) subjects and a wide spectrum of non-NFA subjects. Each subject was asked to stop breathing at end-expiration. Dyspnea was assesssed by a modified Borg scale. To design the new index, we combined the Borg score at the end of the voluntary breath-holding maneuver with the airway limitation. The equation was as follows: FEV(1)/FVC%/(breath-holding time in seconds/final Borg score minus basal Borg score). RESULTS: Eleven NFA subjects (4 females) aged 21-73yr and 55 non-NFA (14 severe, 18 moderate and 23 mild asthmatic subjects) completed the study. The threshold value of the index that could predict POD is <12. The mean (+/-sd) of the new index perception was significantly lower in NFA group (n=11; 5.21+/-3.59; vs. n=55; 13.67+/-11.08; P=0.006). This threshold value had 100% sensitivity and it best discriminated between mild and NFA groups. The negative likelihood ratio (when the index > or = 12) was zero. A result > or = 12 represented an almost null probability of poor POD. CONCLUSION: The breath-holding test is simple and rapid. Its negative likelihood ratio was zero. Accordingly, a test result of 12 or greater might exclude the probability of poor perception of dyspnea in subjects with stable asthma. ( view less ) Adriana Garozzo,Christian C C Cutri,Christophe Pannecouque,Angelo Castro,Francesco Guerrera,Erik De Clercq We recently described the synthesis and antiviral activity of the compounds 5-phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-isothiazolecarbonitrile and S-(4-cyano-5-phenylisothiazol -3-yl)-O-ethyl thiocarbonate, which were found to be effective against both HIV-1 (IIIB) and HIV-2 (ROD). ... ( view more )We have now evaluated these compounds against both RNA and DNA viruses, obtaining high selectivity indexes for poliovirus 1 (SI: 223 and 828, respectively) and Echovirus 9 (SI: 334 and 200, respectively). In our previous studies, 3-methylthio-5-(4-OBn-phenyl)-4-isothiazolecarbonitrile was found to exhibit a broad spectrum of action against picornaviruses, we therefore selected this compound and S-(4-cyano-5-phenylisothiazol-3-yl)-O-ethyl thiocarbonate as the model for the synthesis of a new isothiazole derivative, S-[4-cyano-5-(4-OBn-phenyl)isothiazol-3-yl]-O-ethyl thiocarbonate. This compound was evaluated against picornaviruses, measles virus, HIV-1 (IIIB) and HIV-2 (ROD), and some DNA viruses (adenovirus type 2 and herpes simplex virus type 1). The compound was shown to be active against rhinoviruses 2, 39, 86 and 89, Coxsackie B1 and measles virus. ( view less ) Carla Perria,Donatella Mandolini,Carmelina Guerrera,Tom Jefferson,Paolo Billi,Virgilio Calzini,Alfonso Fiorillo,Giuseppe Grasso,Sergio Leotta,Walter Marrocco,Concetta Suraci,Amina Pasquarella BACKGROUND: In Italy many diabetics still lack adequate care in general practice. We assessed the effectiveness of different strategies for the implementation of an evidence-based guideline for the management of non-complicated type 2 diabetes among General Practitioners (GPs) of Lazio region. METH... ( view more )ODS: Three-arm cluster-randomised controlled trial with GPs as units of randomisation (clusters). 252 GPs were randomised either to an active strategy (training module with administration of the guideline), or to a passive dissemination (administration of the guideline only), or to usual care (control). Data on prescriptions of tests and drugs were collected by existing information systems, whereas patients' data came from GPs' databases. Process outcomes were measured at the cluster level one year after the intervention. Primary outcomes concerned the measurement of glycosilated haemoglobin and the commissioning of micro- and macrovascular complications assessment tests. In order to assess the physicians' drug prescribing behaviour secondary outcomes were also calculated. RESULTS: GPs identified 6395 uncomplicated type 2 patients with a high prevalence of cardiovascular risk factors. Data on GPs baseline performance show low proportions of glycosilated haemoglobin assessments. Results of the C-RCT analysis indicate that the active implementation strategy was ineffective relating to all primary outcomes (respectively, OR 1.06 [95% IC: 0.76-1.46]; OR 1.07 [95% IC: 0.80-1.43]; OR 1.4 [95% IC:0.91-2.16]. Similarly, passive dissemination of the guideline showed no effect. CONCLUSION: In our region compliance of GPs with guidelines was not enhanced by a structured learning programme. Implementation through organizational measures appears to be essential to induce behavioural changes. TRIAL REGISTRATION: ISRCTN80116232. ( view less ) S Catania,A Germanà,R Cabo,F J Ochoa-Erena,M C Guerrera,J Hannestad,J Represa,J A Vega Neurotrophins (NTs) and their signal transducing Trk receptors play a critical role in the development and maintenance of specific neuronal populations in the nervous system of higher vertebrates. They are responsible for the innervation of the inner ear cochlear and vestibular sensory epithelia. N... ( view more )eurotrophins and Trks are also present in teleosts but their distribution in the inner ear is unknown. Thus, in the present study, we used Western-blot analysis and immunohistochemistry to investigate the expression and cell localization of both NTs and Trk receptors in the inner ear of alevins of Salmo salar and Salmo trutta. Western-blot analysis revealed the occurrence of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not nerve growth factor (NGF), as well as all three Trk receptors, i.e. TrkA, TrkB and TrkC, the estimated molecular weights of which were similar to those expected for mammals. Specific immunoreactivity for neurotrophins was detected mainly in the sensory epithelia. In particular, BDNF immunoreactivity was found in the maculae of the utricle and saccule, whereas NT-3 immunoreactivity was present in the sensory epithelium of the cristae ampullaris. As a rule the sensory epithelia of the inner ear lacked immunoreactivity for Trks, thus excluding possible mechanisms of autocrinia and/or paracrinia. By contrast, overlapping subpopulations of neurons in the statoacoustic ganglion expressed TrkA (about 15%), TrkB (about 65%) and TrkC (about 45%). The present results demonstrate that, as in mammals and birds, the inner ear of teleosts expresses the components of the neurotrophin-Trk system, but their roles remain to be elucidated. ( view less ) Diane Appelbaum,Benjamin Kligler,Bruce Barrett,Moshe Frenkel,Mary P Guerrera,Kofi A Kondwani,Bennett B Lee,Ellen Tattelman The Institute of Medicine's (IOM's) Academy of Science has recommended that medical schools incorporate information on CAM (complementary and alternative medicine) into required medical school curricula so that graduates will be able to competently advise their patients in the use of CAM. The repor... ( view more )t states a need to study models of systems that integrate CAM and allopathic medicine. The authors present Cuba's health care system as one such model and describe how CAM (or natural and traditional medicine) is integrated into all levels of clinical care and medical education in Cuba. The authors examine the Cuban medical school curriculum in which students, residents, and practicing physicians are oriented in the two paradigms of CAM and allopathic medicine. Only health professionals are permitted to practice CAM in Cuba; therefore, Cuba's medical education curriculum incorporates not only teaching about CAM, but it also teaches basic CAM approaches and clinical skills. Both the theory and practice of CAM are integrated into courses throughout the six-year curriculum. Similarities and differences between the U.S. and Cuban approaches to CAM are examined, including issues of access and cost, and levels of acceptance by the medical profession and by the public at large in both countries. The authors conclude that there is potentially much to learn from the Cuban experience to inform U.S. medical educators and institutions in their endeavors to comply with the IOM recommendations and to incorporate CAM into medical school curricula. ( view less ) A M Vignola,L Riccobono,M Profita,A Foresi,R Di Giorgi,D Guerrera,M Gjomarkaj,P Di Blasi,P L Paggiaro In asthma a dysregulation of eosinophil apoptosis and an imbalance of metalloproteinase-9 (MMP-9) and tissue inhibitor metalloproteinase-1 (TIMP-1) play an important role in airway inflammation and remodelling. We evaluated the effects of a low dose of inhaled fluticasone proprionate (FP) (100 micr... ( view more )og bid by Diskus) for 4 weeks in 24 steroid naive patients with mild persistent asthma, symptomatic and with a sputum eosinophilia >or=3% on clinical outcomes and inflammatory markers such as the induced sputum eosinophils, the induced sputum apoptotic eosinophils, the levels of MMP-9 and TIMP-1 and their molar ratio in the induced sputum supernatants. After FP treatment forced expiratory volume (FEV1) and FEV1/forced vital capacity values, PEF (L/min), sputum apoptotic eosinophils, and MMP-9/TIMP-1 molar ratio in sputum supernatants of asthmatic subjects were significantly increased in comparison with baseline, while sputum eosinophils significantly decreased. Change (Delta) in FEV1 after treatment with FP negatively correlated with the Delta in sputum eosinophils, while the Delta in MMP-9 values positively correlated with Delta in TIMP-1 values. This study shows that the clinical improvement achieved by the use of low doses of FP in asthmatics is related, at least in part, to the resolution of eosinophilic inflammation and the downregulation of remodelling markers. ( view less ) A Marrone,R Zampino,P Karayannis,G Cirillo,G Cesaro,B Guerrera,R Ricciotti,E Miraglia del Giudice,R Utili,L E Adinolfi,G Ruggiero BACKGROUND: Drug-resistant mutants may emerge in patients with chronic hepatitis B receiving lamivudine therapy. AIM: To evaluate whether different viral mutational patterns may be associated with clinical reactivation during lamivudine treatment in patients with chronic B hepatitis. METHODS: Eight... ( view more ) anti-hepatitis B e-positive patients with (group A) and 14 patients without clinical exacerbation (five anti-hepatitis B e-positive, group B1; nine hepatitis B e antigen-positive, group B2) during lamivudine treatment were investigated. RESULTS: 'Polymerase region': M204V/I variants were found in all group A patients, but in none of group B1 (P=0.0007) and in four of nine of group B2 (44%; P=0.02) patients. The L180M substitution was detected in four of eight (50%) of group A and in none of groups B1 and B2. 'Core promoter': the double basic core promoter (A1762T/G1764A) variant was detected in seven of eight (87%) of group A and in one of five (20%; P=0.03) of group B1 and one of nine (11%; P=0.002) of group B2 patients. 'Precore': the G1896A stop codon mutation was present in seven of eight (87%) of group A and in zero of five (P=0.004) of group B1 and one of nine (11%; P=0.002) of group B2. CONCLUSIONS: Different mutational patterns were observed in the lamivudine-treated patients with and without exacerbation. There was an association of the basic core promoter and stop codon mutations with lamivudine resistance in patients with disease exacerbation. ( view less ) Nicola De Luca,Raffaele Izzo,Guido Iaccarino,Pier Luigi Malini,Carmine Morisco,Francesco Rozza,Gianni Luigi Iovino,Maria Assunta Elena Rao,Clara Bodenizza,Francesca Lanni,Luigi Guerrera,Oreste Arcucci,Bruno Trimarco BACKGROUND: Inadequate blood pressure (BP) control could be due to incorrect management of hypertensives caused by the lack of interaction between general practitioners (GP) and hypertension specialists. OBJECTIVES: To test the effectiveness on BP and total cardiovascular risk (TCVR) control of an ... ( view more )internet-based digital network connecting specialists and GPs. METHODS: We created a network among the Hypertension Clinic, Federico II University (Naples, Italy), 23 hospital-based hypertension clinics and 60 GPs from the area (CampaniaSalute Network, CS). Randomized GPs enrolled in CS could update online records of patients (n = 1979). As a control, we included 2045 patients referred to the specialist clinics by GPs from outside the network. All patients completed a 2-year follow-up. RESULTS: CS provided a larger reduction in BP [systolic/diastolic BP (SBP/DBP): 7.3 +/- 0.4/5.4 +/- 0.3 versus 4.1 +/- 0.4/3.1 +/- 0.26 mmHg, CS versus control; P < 0.001 for both] and percentage of patients with BP < 140/90 mmHg (CS versus control: baseline, 33 versus 34%, NS; end of follow-up, 51 versus 47%, chi = 13.371; P < 0.001). A European Society of Hypertension-European Society of Cardiology (ESH/ESC) TCVR score was calculated [from 1 (average) to 5 (very high TCVR)]. The CS group showed a reduction in the mean TCVR score (CS: from 3.5 +/- 0.02 to 3.2 +/- 0, P < 0.01, ANOVA; control group: 3.5 +/- 0.03 to 3.4 +/- 0.03, NS) and, accordingly, fatal and non-fatal major cardiovascular events (MACE) were less frequent (2.9 versus 4.3%; chi = 5.047, P < 0.02). CS predicts fewer MACE in multiple binary regression analysis (beta:-7.27, P < 0.008) reducing the risk for MACE compared to control [odds ratio (OR): 0.838; 95% confidence interval (CI): 0.73-0.96]. CONCLUSION: Our results support the idea that telemedicine can achieve better control of BP and TCVR. ( view less )
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