Hydrogen sulfide dysfunction in metabolic syndrome-associated vascular complications involves cGMP regulation through soluble guanylyl cyclase persulfidation.

Here, by using in vitro and ex vivo approaches, we elucidate the impairment of the hydrogen sulfide (H2S) pathway in vascular complications associated with metabolic syndrome (MetS). In the in vitro model simulating hyperlipidemic/hyperglycemic conditions, we observe significant hallmarks of endothelial dysfunction, including eNOS/NO signaling impairment, ROS overproduction, and a reduction in CSE-derived H2S. Transitioning to an ex vivo model using db/db mice, a genetic MetS model, we identify a downregulation of CBS and CSE expression in aorta, coupled with a diminished L-cysteine-induced vasorelaxation. Molecular mechanisms of eNOS/NO signaling impairment, dissected using pharmacological and molecular approaches, indicate an altered eNOS/Cav-1 ratio, along with reduced Ach- and Iso-induced vasorelaxation and increased L-NIO-induced contraction. In vivo treatment with the H2S donor Erucin ameliorates vascular dysfunction observed in db/db mice without impacting eNOS, further highlighting a specific action on smooth muscle component rather than the endothelium. Analyzing the NO signaling pathway in db/db mice aortas, reduced cGMP levels were detected, implicating a defective sGC/cGMP signaling. In vivo Erucin administration restores cGMP content. This beneficial effect involves an increased sGC activity, due to enzyme persulfidation observed in sGC overexpressed cells, coupled with PDE5 inhibition. In conclusion, our study demonstrates a pivotal role of reduced cGMP levels in impaired vasorelaxation in a murine model of MetS involving an impairment of both H2S and NO signaling. Exogenous H2S supplementation through Erucin represents a promising alternative in MetS therapy, targeting smooth muscle cells and supporting the importance of lifestyle and nutrition in managing MetS.

Determinants of health-related quality of life in morbid obese candidates to gastric banding.

OBJECTIVE: To analyse determinants of self reported health-related quality of life (HR-QoL) in morbid obese patients candidates to laparoscopic adjustable gastric banding (LAGB). METHODS: Determinants of HR-QoL were investigated in 383 morbid obese patients (82 M and 301 F) with BMI≥40 kg/m² (BMI≥35 kg/m² if complicated obesity) and age 18-60 years. HR-QoL was determined with the SF-36 questionnaire. Determinants of the two summary measures of SF-36 (physical component and mental component) were analysed by stepwise multiple linear regression analysis with age, BMI, physical comorbidites, mental comorbidites and eating behaviour disorders as independent variables. Physical comorbities (diabetes, hypertension, hypertriglyceridemia, low HDL, sleep apnea and osteoarthritis) were coded as present or absent on the basis of simple diagnostic clinical criteria; mental comorbidities (depression) and eating behaviour disorders (binge eating, sweet eating and nibbling) on the basis of an unstructured clinical interview. RESULTS: Mean age was 38.8±10.2 years and mean BMI was 41.5±5.4 kg/m². Scores in the eight SF-36 subscales were lower in women than in men and lower than in the general Italian population. However, 18.4-43.5% of the participants had HR-QoL levels above the normative values, depending on the scale. In both genders, low scores in the mental component of the SF-36 were associated to the presence of depression and eating behaviour disorders and not to physical comorbidities or BMI levels. Low physical self-perceived well being was associated to high BMI levels in men and to depression, hypertension and hypertriglyceridemia in women. CONCLUSION: HR-QoL was poor in morbid obese candidates to LAGB, particularly in women, and was negatively affected more by mental comorbidites and eating behaviour disorders than by physical comorbidities or BMI levels.

[Aorto-mesenteric compression syndrome. Description of clinical case and critical review of the literature]. / La sindrome del compasso aorto-mesenterico. Descrizione di un caso clinico e revisione critica della letteratura.

Aorto-mesenteric duodenal compression syndrome is a rare disease in which superior mesenteric artery causes a substenosis of the duodenum. Pathogenesis of this syndrome is due to congenital or acquired factors. Symptomatology is usually non specific and intermittent. Diagnosis is given by selective superior mesenteric artery angiography. Therapy is only surgery.

[The right laparoscopic adrenalectomy of an incidentaloma]. / Surrenectomia destra laparoscopica di un incidentaloma.

The authors report a case of incidental lesion of right adrenal gland in a 56-years-old patient, followed for a liver disfunction. The lesion, with cystic and hemorrhagic histological characters, was treated with laparoscopic resection. The following case report covers the diagnostic procedures, laparoscopic technique, showing the advantages, and postoperative course in surrenal lesion without local infiltration.

Characterization of functional regions in the Schizosaccharomyces pombe mei3 developmental activator.

The Schizosaccharomyces pombe mei3(+) gene is expressed only in diploid cells undergoing meiosis. Ectopic expression of mei3(+) in haploid cells causes meiotic catastrophe. Mei3 is an inhibitor of Ran1/Pat1 kinase and contains a nine-amino-acid motif, Mei3-RKDIII, that resembles two regions in the Ste11 substrate for Ran1/Pat1. Substitution of serine for Arg-81 within Mei3-RKDIII transforms the inhibitor into a substrate for Ran1/Pat1. Thus, it is likely that Mei3-RKDIII defines a pseudosubstrate sequence. In this study, we constructed a series of mei3 deletion mutations and assayed each for activity. This analysis indicates that the carboxy-terminal domain of Mei3 is sufficient for function in vivo. Alanine-scanning mutagenesis identifies critical residues within the inhibitory domain. Two mutations, SM1 and SM8, fail to cause meiotic catastrophe. The SM1 mutation contains alterations of amino acid residues in Mei3-RKDIII. Recombinant SM1 protein exhibits reduced ability to inhibit Ran1/Pat1 kinase in vitro and interacts inefficiently with the kinase in a two-hybrid assay. The SM8 protein binds to Ran1/Pat1 in a two-hybrid assay but fails to inhibit Ran1/Pat1 substrate phosphorylation in vitro. These findings provide evidence that Mei3-RKDIII defines a Ran1/Pat1-binding site that is necessary but not sufficient for inhibition of the kinase. Using fusions to green fluorescent protein, the cellular localization of Ran1 and Mei3 was examined in living cells. Ran1 is concentrated in the nucleus. Mei3 is also enriched in the nucleus and, consistent with the genetic and biochemical results, the inhibitory domain of Mei3 is sufficient for nuclear localization.

Intestinal occlusion secondary to Morgagni-Larrey's herniation in an adult. Case report and analysis of the literature.

Morgagni-Larrey's hernias are congenital diaphragmatic hernias, rarely observed and generally identified accidentally due to the lack of symptoms. The authors report a case of intestinal occlusion secondary to Morgagni-Larrey herniation in an adult recently observed and underline the aetiopathogenic aspects, the diagnostic tools and the clinical pattern. They suggest to consider surgical repair as a choice of treatment, also for asymptomatic patients.

[Adenomyomatosis of the gallbladder. Our experience]. / L'adenomiomatosi della colecisti. Nostra esperienza.

Adenomyomatosis is a rare affection of the gallbladder and it's infrequently reported in the Literature. Having observed eighteen cases of adenomyomatosis of the gallbladder in the last five years and considering the difficulties in making an early diagnosis of gallbladder cancer, the authors suggest the importance of cholecystectomy in this pathology.

[Laparoscopy in iatrogenic lesions of the colon during operative endoscopy]. / La laparoscopia nelle lesioni iatrogene del colon in corso di endoscopia operativa.

Colonscopy is a standard diagnostic and therapeutic procedure that has its own morbidity. Colonic perforation is the dangerous complication of this procedure. Successful management of perforation by conservative or surgical treatment remains controversial. We report two cases, recently observed, of patients with colonic perforation occurring during therapeutic colonscopy treated with minimally invasive technique.

[Contribution of a combination of alpha and beta benzopyrones, flavonoids and natural terpenes in the treatment of lymphedema of the lower limbs at the 2d stage of the surgical classification]. / Contributo di un'associazione di alpha e beta benzopironi, flavonoidi e terpeni di derivazione naturale, nel trattamento del linfedema degli arti inferiori al II stadio della classificazione operativa.

HYPOTHESIS: To create a phlebolymphologic therapy in order: to activate venous system; to activate lymphatic system; to activate macrophagic system; to reduce the proteic lymphatic load. EXPERIMENTAL: A study was performed on the use of an ideal phlebolymphological association (Tonka Beans, Gingko Biloba, Melilotus Officinalis) as a practical standpoint in the treatment of lymphedema of lower limbs in order to create an efficacious dose of Coumarin, Benzopyrones and Ginkolidi. CLINICAL: We investigated a population of 76 patients treated in an open-label study for six-eight months with a dosage of Coumarin 60 mg/daily + Gingko Biloba 40 mg/daily + Melilotus 40 mg/daily. CONCLUSION: This trilogy induced a very significant improvement in lymphedema (centimeter-aspect) both in functional symptoms (pain heaviness in affected limbs) and physical signs (edema, episodes of infection). Tolerance of long term treatment was good and the improvement was observed from the third month of treatment.

Dose-dependent visible effect on mice Langerhans cell membrane markers.

Ultraviolet B and psoralen plus UVA treatment induce antigenic and enzymatic changes in Langerhans cells (LC). The aim of this study was to investigate the visible (VIS) effect on mice LC surface markers. As visible source, a slide projector equipped with a 150-W tungsten lamp, emitting between 400 and 740 nm (maximum at 580 nm) was used. Mice (BALB/c and C3H) were divided into groups, each irradiated with visible single fixed doses (ranging from 10 to 1000 J/cm2). The mice backs were shaved before irradiation. Skin biopsies obtained immediately after irradiation were processed for immunofluorescence and electron microscopy. Immunofluorescent studies showed: 1) a complete depletion of LC membrane markers at a dose of 700 J/cm2; 2) no effect at visible doses ranging between 0 and 75 J/cm2; 3) a dose-dependent effect with doses between 100 and 700 J/cm2. Electron microscopy revealed no cellular damage of LC at the visible doses administered.

Determinaçäo de receptores hormonais em câncer de mama: método histoquimico / determination of hormonal receptors breast cancer: histochemical method

Em 31 biópsias de pacientes portadores de câncer de mama foram realizados diagnóstico histopatológico e avaliaçäo do status hormonal. A técnica histoquímica usada para o estudo de receptores de estrogênio e progesterona (ER e PgR) em cortes criostáticos é simples e de fluorescência alternativa. Cortes adjacentes foram corados por hematoxilina-eosina (HE) e laranja de acridina (AO) para diagnóstico e identificaçäo da populaçäo celular maligna. Achados preliminares mostram: 1) dos tumores estudados, 38,7% foram positivos, 12,9% duvidosos e 48,4% negativos. 2) Maior freqüência de ER e PgR foi encontrada nas pacientes pós-menopáusicas. 3) O carcinoma lobular infiltrante apresentou elevada positividade para ER e PgR. 4) Valores baixos de ER e PgR foram encontrados em tumores com infiltrado linfocitário intenso. 5) A populaçäo heterogênica que forma os tumores malignos de mama está constituída por células ER e PgR positivas e negativas em diversas proporçöes. Os autores também relatam observaçöes sobre a presença de receptores nucleares e dados morfológicos

Infecciones humans por Flavivirus en Tandil. / Human infections by Flavivirus in Tandil

Se analizaron 336 sueros humanos obtenidos entre el 24-4-79 y el 26-11-81, del partido de Tandil, para determinar la presencia o no en esta latitud de 3 Flavivirus conocidos para la Republica Argentina. Se pudo establecer las actividades de los virus encefalitis de San Luis e Ilheus.No ha habido actividad de fiebre amarilla a pesar de que algunos de los individuos encuestados tienen mas de 80 anos. Se admite la existencia a otro/s Flavivirus aun no identificado/s, diferente a los dos (SLE e ILH) ya constatados como endemicos

Infecciones humans por Flavivirus en Tandil. / Human infections by Flavivirus in Tandil

Se analizaron 336 sueros humanos obtenidos entre el 24-4-79 y el 26-11-81, del partido de Tandil, para determinar la presencia o no en esta latitud de 3 Flavivirus conocidos para la Republica Argentina. Se pudo establecer las actividades de los virus encefalitis de San Luis e Ilheus.No ha habido actividad de fiebre amarilla a pesar de que algunos de los individuos encuestados tienen mas de 80 anos. Se admite la existencia a otro/s Flavivirus aun no identificado/s, diferente a los dos (SLE e ILH) ya constatados como endemicos