Oxidative stress enhances and modulates protein S-nitrosation in smooth muscle cells exposed to S-nitrosoglutathione.

Among S-nitrosothiols showing reversible binding between NO and -SH group, S-nitrosoglutathione (GSNO) represents potential therapeutics to treat cardiovascular diseases (CVD) associated with reduced nitric oxide (NO) availability. It also induces S-nitrosation of proteins, responsible for the main endogenous storage form of NO. Although oxidative stress parallels CVD development, little is known on the ability of GSNO to restore NO supply and storage in vascular tissues under oxidative stress conditions. Aortic rat smooth muscle cells (SMC) were stressed in vitro with a free radical generator (2,2'-azobis(2-amidinopropane) dihydrochloride, AAPH). The cellular thiol redox status was reflected through levels of reduced glutathione and protein sulfhydryl (SH) groups. The ability of GSNO to deliver NO to SMC and to induce protein S-nitrosation (investigated via mass spectrometry, MS), as well as the implication of two redox enzymes involved in GSNO metabolism (activity of gamma-glutamyltransferase, GGT, and expression of protein disulfide isomerase, PDI) were evaluated. Oxidative stress decreased both intracellular glutathione and protein -SH groups (53% and 32% respectively) and caused a 3.5-fold decrease of GGT activity, while PDI expression at the plasma membrane was 1.7-fold increased without any effect on extracellular GSNO catabolism. Addition of GSNO (50 µM) increased protein -SH groups and protein S-nitrosation (50%). Mass spectrometry analysis revealed a higher number of S-nitrosated proteins under oxidative stress (83 proteins, vs 68 in basal conditions) including a higher number of cytoskeletal proteins (15, vs 9 in basal conditions) related with cell contraction, morphogenesis and movement. Furthermore, proteins belonging to additional protein classes (cell adhesion, transfer/carrier, and transporter proteins) were S-nitrosated under oxidative stress. In conclusion, higher levels of GSNO-dependent S-nitrosation of proteins from the cytoskeleton and the contractile machinery were identified under oxidative stress conditions. The findings may prompt the identification of suitable biomarkers for the appraisal of GSNO bioactivity in the CVD treatment.

Endothelin system mRNA variation in the heart of Zucker rats: evaluation of a possible balance with natriuretic peptides.

BACKGROUND AND AIMS: The deregulation of neurohormonal systems, including the natriuretic peptide (NP) and endothelin (ET) systems, may increase the possibility of developing obesity-related risk. The aim of our paper was to evaluate ET system mRNA variation in heart of the Zucker rat model together with the simultaneous evaluation of the NP system transcriptomic profile. In order to analyze the link between the ET-1 system and the inflammatory process, the cardiac expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α was also measured. METHODS AND RESULTS: Zucker rats of 11-13 weeks were subdivided into obese rats (O, n = 20) and controls (CO, n = 20): half of them were studied under fasting conditions (CO(fc)-O(fc)) and the remainder after the induction of acute hyperglycemia (CO(AH)-O(AH)). Cardiac mRNA expression of TNF-α, IL-6, and NP/ET-1 systems was evaluated by Real-Time polymerase chain reaction. No significant difference for pre-proET-1, ET-A, and ET-B mRNA expression was detected between O and CO, whereas significantly lower mRNA levels of the ECE-1 were observed in O (p = 0.02). Regarding NPs, only BNP mRNA expression decreased significantly in O with respect to CO (p = 0.01). A down-regulation of NPR-B and NPR-C and an up-regulation of NPR-A were observed in O. No significant difference for IL-6 and TNF-α mRNA was revealed. Subdividing into fasting and hyperglycemic rats, many of the genes studied maintained their mRNA expression pattern almost unchanged. CONCLUSIONS: The modulation of ET-1/NP systems in obesity could be a useful starting point for future studies aimed at identifying new therapeutic strategies for the treatment of cardiometabolic syndrome.

[Obstructive jaundice caused by residual and/or recurrent choledochal lithiasis: endoscopic and surgical treatment]. / Ittero ostruttivo da litiasi residua e/o recidiva del coledoco: trattamento endoscopico e chirurgico.

Results of surgical and endoscopic treatment in 79 patients (58 females and 21 males, age 40-89, mean 62), affected with jaundice, due to secondary choledochal lithiasis, are reported. Thirty-four patients (43%) underwent surgical operation: choledochotomy and T-tube 12, choledocho-jejunostomy 4, choledochoduodenostomy 3, papillosphincteroplasty 15. In 45 patients (57%) EST has been performed. Comparison of results has been obtained after 30 days and after 3-105 months (mean 49). Optimal results have been achieved in 94.9% of patients: 100% after surgery and 94.1% after EST. Morbidity and mortality outcomes in patients who underwent EST (11.1% and 0% after 30 days respectively, 8.1% and 8.1% after several months) are better compared to those ones after surgical treatment (17.6% and 5.8% after 30 days, 20% and 16% after several months). We conclude that EST is nowadays the therapy of choice in patients with jaundice due to choledochal lithiasis, either relapsing or residual.

[Treatment of breast carcinoma. Our experience]. / Il trattamento del carcinoma della mammella. Nostra esperienza.

The results of a study on 848 patients with breast carcinoma having maximum diameter less than or equal to 2 cm, that underwent a surgical treatment at the Institute of Special Surgical Pathology B (1980-82) and at the Institute of Surgical Clinic I (1980-89) are presented. The study has the purpose of evaluating, by the analysis of ten years surviving curves, the effectiveness of different types of interventions: Halsted radical mastectomy (98 patients), Patey radical mastectomy (245 patients) and Madden radical mastectomy (151 patients), quadrantectomy (260 patients). The age of patients ranges from 29 years to 92 years (average 56 years). The 68.04% of all tumors have resulted invasive ductal carcinoma (NOS) the 9.08% lobular carcinoma. Of the 848 patients included in the study 698 are alive at the end of the follow-up, with a survival rate, calculated with the actuarial method, equivalent to 63.38%. Results show the survival is independent of the type of surgical treatment (71.9% for quadrantectomy; 70.7% for Halsted radical mastectomy, 68.9% for Patey radical mastectomy; 70.7% for Madden radical mastectomy).(ABSTRACT TRUNCATED AT 250 WORDS)

[The ileocecal valve as a prognostic factor in extensive resection of the small intestine]. / La valvola ileociecale quale fattore prognostico nelle resezioni estese dell'intestino tenue.

The aim of the study was to examine the role of the ileocaecal valve in relation to the nature and extent of symptoms following extensive bowel resection (EBR) in 13 patients with short bowel syndrome (SBS) referred to our department over the period 1962-1988. The results obtained do not allow us to assess the effective role of the ileocaecal valve in determining the severity of SBS. The factors conditioning the extent of the aftermath of EBR and effectively affecting prognosis are, in fact, multiple and act in various interrelated ways, thus making it difficult to define the precise role of any one of them. The ileocaecal valve, however, does play a substantial role, in that, on the one hand, it performs sphincter and barrier functions against ileocolic reflux of bacteria, while, on the other, its removal involves excision of the right colon (reserve area for reabsorption of water and ions) and of the terminal ileum (a site specialized in absorption of vitamin B12 and bile salts).

[A case of small-cell carcinoma of the rectum]. / Su un caso di carcinoma a piccole cellule del retto.

A case of oat-cell carcinoma of the rectum prompted the authors to undertake a review of the literature. The main histological aspects allowing an accurate diagnosis are stressed. This is a rare form of highly malignant neoplasm of uncertain origin (probably similar to that of carcinoids) with a very marked tendency to metastasize, even to distant organs; it is characterized by substantial cellular polymorphism with small-sized elements, very little cytoplasm, a large hyperchromic nucleus, barely visible nucleoli and histochemical reactions typical of neuroendocrine cells.

[A case of leiomyosarcoma of the small intestine. Clinical and anatomopathologic considerations]. / Su un caso di leiomiosarcoma del tenue. Considerazioni cliniche ed anatomopatologiche.

Leiomyosarcoma of the small intestine is a malignant mesenchymal tumour composed of smooth muscle cells from the muscular coat or, rarely, from muscularis mucosae, which in the majority of cases is characterised by a clinically silent development and by an unfavorable prognosis. The considerable difficulty of obtaining a histological definition of the degree of malignancy of the leiomyosarcoma is also typical. The paper reports a clinical case and summarises its main clinical and anatomopathological aspects. In particular, the difficulties of clinical and histological diagnosis of the degree of malignancy are underlined, together with the fact that these have a considerable influence on the possibilities and results of surgical therapy and survival rates.

[Treatment of recurrent or residual calculosis of the choledochus. A comparison of the technics]. / Il trattamento della calcolosi recidiva o residua del coledoco. Tecniche a confronto.

The results of treating residual or recurrent calculosis of the choledochus for the purpose of obtaining elements for deciding whether or not to carry out a given operation in a particular group of patients are reported. Although they do not offer elements of certainty, the results still make it possible to arrive at an indication for endoscopic papillotomy in elderly patients in poor general condition with one or a few calculi and non-dilated choledochus, for choledochotomy in patients with choledochus of normal diameter and with multiple calculi, or for an intervention of biliodigestive drainage (particularly choledochojejunostomy) in patients with multiple calculosis and with dilated choledochus. In cases in which the apparatus of Oddi is the site of an irreversible inflammatory process and has lost its function, transduodenal papillosphincterotomy is justified.

[Results of endoscopic treatment of choledochal calculosis and cicatricial stenosis of the papilla]. / Risultati con il trattamento endoscopico nella calcolosi del coledoco e nella stenosi cicatriziale della papilla.

The results obtained with endoscopic papillo-sphincterotomy in the treatment of gallstones and cicatricial stenosis of the papilla are reported. The treatment proved effective in 91.3% of patients with papillary stenosis and the incidence of side-effects (cholangitis, pancreatitis, bleeding, perforation) was 7.5%. Endoscopic PST hitherto restricted to cases judge inoperable due to serious concomitant pathologies may be a valid alternative to surgery wherever total sphincter dysfunction can be ascertained.

[Use of vasopressin in the treatment of acute hemorrhagic lesions of the stomach. Our experience]. / Impiego della vasopressina nel trattamento delle lesioni emorragiche acute dello stomaco. Nostra esperienza.

Since bleeding from acute lesions of the gastric mucosa can cease spontaneously and the mortality rate of emergency surgery is high, conservative treatment is always preferable. Satisfactory results were obtained with continuous infusions of vasopressin in low doses (0.2 U/kg/hr for 8 hours) so that this treatment appears a valid alternative to more recent techniques (somatostatin).

[Use of vasopressin in the treatment of bleeding esophageal varices. Our experiences]. / Impiego della vasopressina nel trattamento delle varici esofagee sanguinanti. Nostra esperienza.

Results obtained in the control of oesophageal varix rupture haemorrhage by intravenous vasopressin perfusion or selective intraarterial administration are reported. This comparative study shows intravenous administration to be the best method since it produces the same therapeutic effects with fewer undesirable side-effects than when administered arterially. In view of the high level of complications caused by selective arterial catheters, this administration method would only appear justified in cases where selective arterial catheterisation is to be carried out in any case.