Centella asiatica and lipoic acid, or a combination thereof, inhibit monocyte adhesion to endothelial cells from umbilical cords of gestational diabetic women.

BACKGROUND AND AIMS: Diabetes mellitus is associated with inflammatory endothelial activation and increased vascular leukocyte adhesion molecule expression, both playing a prominent role in the development of vascular complications. Centella asiatica (CA) and Lipoic Acid (LA) have shown anti-inflammatory and anti-oxidant properties in a variety of experimental models; however, their action on human umbilical vein endothelial cells (HUVECs), chronically exposed to hyperglycemia and pro-inflammatory environment during pregnancy, is still unknown. METHODS AND RESULTS: In HUVECs from umbilical cords of gestational diabetic (GD) or healthy (C) women, both CA and LA affected tumor necrosis factor-α (TNF-α)-induced inflammation, being associated with a significant decrease in vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression (western blot) and exposure (flow cytometry), as well as monocyte-HUVECs interaction (adhesion assay). Notably, this was associated with a significant reduction of an index of nitro-oxidative stress, such as the intracellular peroxynitrite levels (fluorescence detection by cytometric analysis), Mitogen-Activated Protein kinase (p44/42 MAPK) expression/phosphorylation levels and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB p65) cytoplasm-nucleus translocation (flow cytometry). Overall our results indicate that both CA and LA used separately, and even better when combined, are effective to reduce the inflammatory response in TNF-α-treated HUVECs. Notably, this was more significant in GD than in C-HUVECs and also evident at baseline. CONCLUSION: In conclusion, our in vitro study demonstrates that both CA and LA, or a combination thereof, are able to mitigate the potentially dangerous effects on the endothelium of chronic exposure to hyperglycemia in vivo.

Features of endothelial dysfunction in umbilical cord vessels of women with gestational diabetes.

BACKGROUND AND AIMS: Gestational diabetes (GDM) is associated with increased oxidative stress and overexpression of inflammatory cytokines, both of which might lead to endothelial dysfunction and vascular disease. As such, GDM could be viewed as a sort of 'short lived' metabolic syndrome. As umbilical cord vessels represent a suitable model for the study of vascular alterations brought about by GDM, the aim of the present work was to characterize the phenotype of human umbilical vein endothelial cells (HUVECs) chronically exposed to hyperglycaemia and to a pro-inflammatory environment during pregnancy so as to identify molecular modifications of cellular homoeostasis eventually impacting on endothelial dysfunction. METHODS AND RESULT: Tissue specimens and HUVECs were obtained from umbilical cords of GDMand control women. As compared to controls, GD-HUVEC exhibited enhanced monocyte adhesion and vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1(ICAM-1) expression and exposure on plasma membrane after tumour necrosis factor-alpha(TNF-α) stimulation (Western blot, flow cytometer). As compared to control cells, GD-HUVEC in basal conditions exhibited enhanced monocyte adhesion, nitric oxide synthase (NOS) expression and activity (eNOS Real-Time polymerase chain reaction, Western Blot for eNOS total protein and monomers/dimers ratio, conversion of [3H]-L-arginine in [3H]-L-citrulline), increased O(-)(2)egeneration together with increased NT levels (immunofluorescence) and reduced NO bioavailability(guanosine 3',5'-monophosphate (cGMP) production, EIA). Furthermore, immunohistochemistry revealed increased eNOS and NT immunoreactivity in GD umbilical cords. CONCLUSION: Endothelial cells exposed in vivo even transiently to hyperglycaemia, oxidative stress and inflammation exhibit durable pro-atherogenic modifications.

[Reduced nitric oxide bioavailability in chronic renal failure: a new factor of progression?]. / Ridotta biodisponibilità di ossido nitrico nell'insufficienza renale cronica: un nuovo fattore di progressione?

Nitric oxide (NO) is a gaseous free radical and an important molecular mediator of many physiologic processes in virtually every organ. NO is produced from L-arginine by nitric oxide synthase (NOS). This enzyme is expressed as 3 isoforms, all of which have been isolated from the kidney: endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). At present it is very difficult to measure authentic nitric oxide in vivo; a way to circumvent the difficulties is to study the effects of NOS stimulation and subsequent nitric oxide release directly by measurement of the resulting changes in vascular tone. In the kidney and vasculature, NO plays fundamental roles in the control of systemic and intrarenal hemodynamics, the tubuloglomerular feedback response, pressure natriuresis, release of sympathetic neurotransmitters and renin, and tubular solute and water transport. Chronic renal failure (CRF) is a state of NO deficiency secondary to decreased NO production and/or increased bioinactivation of NO by reactive oxygen species. The purpose of this review is to examine the functions of NO in the kidney, and to discuss the effects of NO deficiency in the progression of chronic kidney disease.

[Spontaneous splenic rupture in a patient with cytomegalovirus infection]. / Rottura spontanea di milza in presenza di infezione citomegalica. Descrizione di un caso clinico.

The Authors report a case of spontaneous splenic rupture in a patient with Cytomegalovirus infection, stress the main characteristics of this infection and describe the mechanism that, during the viral infection, causes morphological and functional alterations of the spleen. The hypersplenism secondary to hyperfunctioning, the formation of immunocomplexes with secondary infarction, mainly of the white pulp, and the disseminated intravascular coagulation are responsible, as in the observed case, of the rupture of splenic capsula. The Authors conclude that the wide diffusion of Cytomegalovirus infection needs the knowledge of all the pathologic signs of this infection to make a timely diagnosis and treatment.

A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia. A multicentric study from the Italian Co-operative Group GIMEMA.

255 patients with acute non-lymphoid leukaemia (ANLL), observed between October 1984 and June 1987, entered a chemotherapy regimen consisting of induction therapy with cytarabine in combination with idarubicin (IDA/ARA) or daunorubicin (DNR/ARA), followed by consolidation with four courses of IDA + ARA plus 6-thioguanine (6-TG) or DNR + ARA + 6-TG and a 6 month maintenance therapy with 6-TG and ARA. The median age was 62 years (range 55-78 years) and 33 were aged more than 70 years. The treatment groups were comparable for median age, FAB type, performance status and initial blood counts. 249 patients were randomised, 124 to the IDA/ARA arm and 125 to the DNR/ARA arm. Complete remission was achieved in 50 patients (40%) on the IDA/ARA treatment program and 49 patients (39%) on DNR/ARA. No definite differences were found between patients receiving IDA/ARA and those treated with DNR/ARA as far as complete response (CR), overall survival, failure free and relapse free survival are concerned. 74% of the complete responders in the IDA/ARA arm and 51% in the DNR/ARA arm achieved CR after a single course of treatment. Resistant leukaemia was observed in 13.7% of the patients in the IDA/ARA arm and in 31.2% in the DNR/ARA one, whereas hypoplastic death occurred in 29% and 14.4%, respectively. In conclusion, our data failed to show any advantage of idarubicin over daunorubicin even though there is some evidence that IDA, despite the higher toxicity, is more rapid in eradicating leukaemia as proved by the higher CR rate obtained after one course of induction.

Medroxyprogesterone acetate: steady-state pharmacokinetics bioequivalence of two oral formulations.

Two micronized oral formulations of medroxyprogesterone acetate (MPA) (Farlutal and Clinovir) were compared in order to evaluate their relative bioavailability. Sixteen female patients with metastatic breast cancer were entered in a randomized cross-over study on 500-mg MPA tablets repeatedly administered (twice daily for 20 days). At the steady state, similar mean +/- SD serum levels of MPA were obtained (131 +/- 44 ng/ml for Farlutal and 136 +/- 45 ng/ml for Clinovir) and the two formulations proved to be bioequivalent (confidence interval at a significance level of 0.95 = 93%-107%).

Use of beta-cyclodextrin in the capillary zone electrophoretic separation of the components of clandestine heroin preparations.

The present paper describes the methodological optimization and validation of a capillary zone electrophoresis method for the rapid determination of heroin, secondary products and additives present in clandestine heroin samples, by using 20 mM beta-cyclodextrins in phosphate buffer, pH 3.23. Applied potential was 15 kV and separation temperature was 24 degrees C; detection was by UV absorption at 200 nm wavelength. Heroin samples were first dissolved in CHCl3-MeOH (96:4, v/v) and injected by pressure (0.5 p.s.i., 3 s; 1 p.s.i.=6894.76 Pa) after evaporation of the organic mixture and reconstitution in aqueous buffer. Under the described conditions, phenylethylamine (internal standard), morphine, monoacetylmorphine, heroin, acetylcodeine, papaverine, codeine and narcotine were baseline resolved in less than 10 min. The limit of detection was better than 1 microg/ml for each analyte. The study of the intra-day and day-to-day precision showed, in terms of migration times, RSDs < or = 0.71% and, in terms of peak areas, RSDs < or = 3.2%. Also, the evaluation of linearity and analytical accuracy of the method provided good results for all the analytes investigated, thus allowing its application to real cases of seized controlled drug preparations.

Epirubicin in non-Hodgkin's lymphomas.

Epirubicin (Epi-DX), a new analog of doxorubicin, was administered I.V. once q 3 weeks at the dose of 90 mg/m2 to 20 evaluable patients with non-Hodgkin's lymphomas (NHL). Eighty-two percent of patients with favorable histology and 67% with unfavorable histology achieved complete or partial remissions, with an overall response rate of 75%. Gastrointestinal and hematologic toxicity was generally mild to moderate. Reversible ST-T changes were observed only in two patients. Epi-DX has high activity in patients with NHL, and further studies in combination with other agents are recommended.

Clinical toxicity of 4'-epi-doxorubicin (epirubicin).

Epirubicin is a new derivative of doxorubicin characterized by an improved spectrum of activity and a better therapeutic index. At equimolar doses and in comparative studies, epirubicin proved to induce less acute toxicity than doxorubicin, in particular less vomiting, hair loss and myelotoxicity. While giving a comparable response rate in randomized breast cancer studies, epirubicin also proved to be less cardiotoxic than doxorubicin. The reduced potential for cardiac toxicity of epirubicin versus doxorubicin has been shown both by functional assessment (radionuclide cinecardioangiography) and by histopathologic evaluation (endomyocardial biopsies) at equally myelosuppressive doses or at equal doses (equimolar). The lessened cardiotoxicity of epirubicin versus doxorubicin can be explained by the different pharmacokinetic and metabolic properties of these two agents: epirubicin has been found to have a more rapid pharmacokinetic plasma clearance and an additional metabolic pathway (unique glucuronidation).

Epirubicin in combination chemotherapy in the treatment of advanced stage non-Hodgkin's lymphomas.

From April 1981 to May 1984, 23 patients with advanced non-Hodgkin's lymphomas were treated with CEOP (cyclophosphamide, epirubicin, vincristine, and prednisone) or OEPP (vincristine, epirubicin, procarbazine, and prednisone) combination chemotherapy. CR was achieved in 58% and PR in 31% of the patients, giving an overall response rate of 89%. Nine of 15 (60%) previously untreated patients with unfavorable histology obtained a CR and 5 a PR. Median relapse-free survival was 33 months; median overall survival has not yet been reached, and the probability of survival for CRs was 91% after 54 months of follow-up. Acute toxicity was quite acceptable, and chronic cardiac toxicity was detected in 6 patients only. In conclusion, epirubicin used in combination chemotherapies induced durable remissions and prolonged survivals in advanced non-Hodgkin's lymphomas.

[GIST of the jejuno-ileal tract]. / I GIST del tratto digiuno-ileale.

Jejunum-ileum stromal tumors give diagnostic and therapeutical problems, especially with regard to histopathological identification and biological behavior. These tumors are very rare in all case report. After gastric stromal tumors these ones are the most frequent of all alimentary tract. They are often incidentally found; because of their potential transformation, they have to be treated by respecting oncologic eradication standards and observing prognostic criteria based on a correct histopathological evaluation (neoplasm localization and dimension, its structure, presence of cytological atypisms, mitotic index, ploidia, surgical resection). Then there has to be a good follow-up program.

[Gastric volvulus. Clinical contribution]. / Il volvolo gastrico. Contributo clinico.

After discussing the classification of the various types of gastric volvulus, the aetiopathogenetic factors that occur in this rare stomach pathology are reviewed. The personal series is reported and the clinical, radiological and above all therapeutic aspects connected with the pathology discussed. It is concluded that, in these cases too, the aims to pursue are the formulation of early diagnosis and implementation of quick, correct treatment for the purpose of eliminating the basic pathology and preventing necrosis of the gastric wall setting in.

[A frequent complication of enterostomy: prolapse]. / Una complicanza frequente delle enterostomie: il prolasso.

Among the other complications of enterostomy, prolapse deserves particular mention on account of the therapeutic problems involved in its correction. Based on a report of the authors' personal experience, the paper focuses on the mechanisms of onset and, above all, on the most appropriate forms of treatment, before continuing to describe the different surgical reparative techniques. In conclusion, the authors affirm that an optimal tailoring of the enterostomy and its appropriate preparation represent the ideal method of preventing the onset of prolapse.

[ Tissue and blood CEA levels in stomach cancer]. / I dosaggi del CEA tissutale e sierico nel carcinoma dello stomaco.

The assays of serum CEA is a useful prognostic marker in patients with stomach cancer. In this study pre-operative serum CEA and tissue CEA in tumour or biopsy were assayed in a group of patients with gastric carcinoma in order to assess their prognostic roles. Based on an analysis of the results the authors affirm that high serum CEA levels in patients with advanced stages of stomach cancer indicate a fatal prognosis, and likewise the finding of tissue CEA in loco-regional lymph nodes at the same concentration as that in the primary tumour is also the sign of a severe prognosis.

[Tumor markers in colorectal cancer]. / I markers tumorali nel cancro del colon-retto.

Over the past ten years numerous studies have been carried out to identify tumour markers able to diagnose cancer of the digestive tract. The paper reports the combined use of some markers (CEA, TPA, GICA, CA 125) in patients with carcinoma of the colon-rectum. The Authors conclude that although these markers are of little use, especially in association, in the early diagnosis of disease, it is very important to utilise these markers to monitor patients following surgical, chemotherapeutic or radiotherapeutic treatment.

[A case of spontaneous hematoma of the rectus abdominis muscle]. / Su di un caso di ematoma spontaneo del muscolo retto addominale.

The authors describe a recently observed case of spontaneous hematoma of the abdominal rectus muscle. They go on from there to a thorough examination of this rare condition in the light of the latest contributions on the subject in the literature. After describing the anatomo-pathological, aetiopathogenetic and clinical aspects of the condition, the authors deal at some length with the diagnostic possibilities afforded by ultrasound in particular and with the indications for conservative therapeutic treatment, surgery being resorted to only in complicated cases or in cases where diagnostic doubts persist.

[Spigelian hernia]. / L'ernia di Spigelio.

The Authors report their experience with the treatment of Spigelian hernia. After addressing the anatomy of the abdominal lateral wall and of etiopathogenic factors responsible for this rare type of hernia, the clinical problems associated with the disease are discussed and the importance of physical examination and instrumental procedures is stressed. The authors then go on to list the possible repair techniques currently available.

[Liver scintigraphy using 99mTc-HIDA in the study of biliary-digestive anastomosis]. / La scintigrafia epato-funzionale con 99mTc-HIDA nello studio delle anastomosi bilio-digestive.

Surgical operations characterised by the creation of a bilio-intestinal anastomosis are becoming an increasingly frequent procedure in bile tract surgery. Just as frequent and well known are the immediate and longer-term postoperative sequelae. Thus, one of the problems which has always interested surgeons and investigators is how best to monitor the functional efficiency of the anastomosis. Traditional x-ray methods, including highly invasive examinations such as PTC and ERCP, as well as the harmless ultrasound procedures do not provide an adequate picture of the functional efficiency of such anastomoses, the only wholly valid and efficacious method being sequential scintigraphy with 99mTc-Hida. On the basis of these principles, the authors describe their experience in this field, stressing the validity of the method, which enables surgeons to study the morphology and, above all, the functional efficiency of bilio-intestinal anastomoses.

[Digestive hemorrhage in portal hypertension: role of sclerotherapy]. / Le emorragie digestive da ipertensione portale: ruolo della scleroterapia.

Haemorrhage is perhaps the most terrible complication of portal hypertension whatever is the etiopathology. The authors point out how sclerotherapy of the varices is either a prophylaxis and a therapeutic procedure with a low rate of local and systemic complications. Even if they are supported by good results in personal experience, the authors notice as important is to tailor the treatment for each patient.