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.

Effects of long-term treatment with pioglitazone on cognition and glucose metabolism of PS1-KI, 3xTg-AD, and wild-type mice.

In this study, we investigated the effects of long-term (9-month) treatment with pioglitazone (PIO; 20 mg/kg/d) in two animal models of Alzheimer's disease (AD)-related neural dysfunction and pathology: the PS1-KI(M146V) (human presenilin-1 (M146V) knock-in mouse) and 3xTg-AD (triple transgenic mouse carrying AD-linked mutations) mice. We also investigated the effects on wild-type (WT) mice. Mice were monitored for body mass changes, fasting glycemia, glucose tolerance, and studied for changes in brain mitochondrial enzyme activity (complexes I and IV) as well as energy metabolism (lactate dehydrogenase (LDH)). Cognitive effects were investigated with the Morris water maze (MWM) test and the object recognition task (ORT). Behavioral analysis revealed that PIO treatment promoted positive cognitive effects in PS1-KI female mice. These effects were associated with normalization of peripheral gluco-regulatory abnormalities that were found in untreated PS1-KI females. PIO-treated PS1-KI females also showed no statistically significant alterations in brain mitochondrial enzyme activity but significantly increased reverse LDH activity.PIO treatment produced no effects on cognition, glucose metabolism, or mitochondrial functioning in 3xTg-AD mice. Finally, PIO treatment promoted enhanced short-term memory performance in WT male mice, a group that did not show deregulation of glucose metabolism but that showed decreased activity of complex I in hippocampal and cortical mitochondria. Overall, these results indicate metabolically driven cognitive-enhancing effects of PIO that are differentially gender-related among specific genotypes.

[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.

Dopamine and serotonin interactions in the prefrontal cortex: insights on antipsychotic drugs and their mechanism of action.

Diminished activity within the prefrontal cortex (PFC) has been associated with many of the cognitive deficits that are observed in schizophrenia. It has been hypothesized that antipsychotic drugs (APDs) used to treat schizophrenia restore normal activity by antagonizing the dopamine (DA) D2 receptor, which is also known to modulate key ionic currents in the PFC. However, the hypothesis that an under-active cortical DA system is responsible for schizophrenic symptoms has been challenged by evidence that newer atypical APDs are weak antagonists at the D2 receptor but potent antagonists at the serotonin (5-HT) 2A receptor . This review examines how DA and 5-HT modulate cortical activity and how they may interact in ways that are relevant to schizophrenia. It is concluded that although D2 receptor antagonism remains a critical factor in restoring impaired cortical activity, effects on 5-HT receptors may act in a synergistic manner on NMDA and GABA currents to potentiate antipsychotic actions in the PFC.

[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.

[Stomach GIST]. / I gist dello stomaco.

Gastric stromal tumors give diagnostic and therapeutic problems, especially with regard to histopathologic identification and biological behavior. These tumors are very rare in all case reports. 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 histopathologic 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.

[Ileum-colon junction benign obstructions]. / Le occlusioni benigne della giunzione ileo-colica.

The Authors discuss on anatomical and functional characteristics of ileum-colon junction, physiological narrowing in alimentary tract and often involved in benign obstruction. They report their series and analyze all inflammatory or not inflammatory diseases potentially involved, by describing them shortly and giving some information about their clinical features and imaging. The treatment of this obstruction will be done as soon as possible, before wall lesions force to make a larger resection.

[Acute pancreatitis: our experience in the light of natural history]. / Pancreatite acuta: nostra esperienza alla luce della sua storia naturale.

The Authors enumerate main steps of acute pancreatitis natural history. Then they discuss their last five years case-report. After having stated that clinical presentation depends on anatomo-pathological conditions, they consider aetiological causes and morphopathogenetic moments involved in the onset and development of this disease. They conclude stating how only proper diagnosis and treatment can prevent its potential evolution in multiorgan failure.

[Mechanical intestinal occlusion due to phytobezoars]. / L'occlusione meccanica intestinale da fitobezoario.

The Authors reporting two cases with ileus by phytobezoar in distal jejunum and ileum, respectively, and discuss the pathophysiologic mechanism responsible for the formation of bezoars. They expose the etiological and clinical factors of this uncommon cause of small bowel obstruction and also discuss the surgical technique that consists in the removal of the phytobezoar through enterotomy.

[A rare salivary gland neoplasm: cystadenolymphoma]. / Una rara neoformazione delle ghiandole salivari: il cistoadenolinfoma.

The authors, after having examined three recent cases, explain some basic concepts about diagnostics and therapy in cystadenolymphoma of salivary glands. As a matter of fact this neoplasia, in spite of its low frequency, is very important because of its still controversial etiopathology and recent tendency in increasing its incidence in females. Today the diagnostic protocol, undertaken after clinical examination, which is necessary, consists of ultrasonography or computerized tomography. But only postoperative histological examination gives a sure diagnosis and can point out main histomorphological characteristics of tumour. Therapeutic approach can be limited to conservative treatment, which is able to respect the parotid gland, its vascularization and innervation.

[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.

[Idiopathic gynecomastia: our experience]. / La ginecomastia idiopatica: nostra esperienza.

The Authors reporting their experience, discuss some concepts about physiologic evolution of male and female breast. They distinguish between real and false gynaecomastia; stressing the causes of abnormal development of male breast and morphopathological characteristics of gynaecomastia. Careful diagnostic protocol is necessary for a therapeutic approach based on traditional surgery or liposuction: it depends on prevalence of glandular or adipose breast's tissue.

[Diagnosis and treatment of Crohn's disease]. / Morbo di Crohn: diagnosi e trattamento.

The Authors state their ideas and report their experience about diagnosis and treatment of Crohn's disease. After having treated risk and etiological factors, they discuss typical anatomo-pathological lesions. Then they explain clinical diagnostic and surgical choices extensively: they prefer laparotomic approach. The Author's conclude that timely diagnosis spare heavy complications.

[Intrahepatic biliary lithiasis: experience in 20 years]. / La litiasi biliare intraepatica: esperienza di 20 anni.

In confirming that intrahepatic gallstones don't represent a frequent disease in western countries, Authors specify how this incidence is going to grow up slowly, but in a progressive way. In reporting their experience since 1980 to nowadays they point out how different diagnostic procedures and therapy way of acting were in the first and in the second deca. After having explained actual therapeutic direction that is described in literature, they finish by stating how this is often conditioned by complex anatomicopathological picture and by seriousness of hepatic damage that often comes with intrahepatic lithiasis.

[Color-Doppler sonographic mapping for the choice of treatment in variceal disease]. / Il mappaggio eco-color-Doppler nella scelta del trattamento della malattia varicosa.

The Authors, after having reported Huch's classification concerning both large and small saphenas varixes, make a short historical excursus about the most significant operative methods. Then they start explaining how a correct therapeutic approach can't be done without a careful hemodynamic study. After having given data about their case-report, they conclude affirming how today the duplex-scanner permits to obtain an excellent radicality also with not very invasive techniques.

[Anastomotic dehiscence in colorectal surgery]. / La deiscenza delle anastomosi in chirurgia colo-rettale.

Anastomotic leakage represents the most dangerous complication in digestive surgery and, particularly, in colorectal one. Indeed a careful evaluation and modification of all possible risk factors and a correct procedure aren't often enough to overcome a potential postoperative leakage or at least material filtration. The Authors review their series to analyse the role of all possible general and local risk factors and to verify what conditions can suggest an two or three stages operation.

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.

[Antibiotic and immunostimulating prophylaxis in colorectal surgery]. / Profilassi antibiotica e immunostimolante in chirurgia colo-rettale.

The Authors, after considering post-operatory sepsis as cause of failures and as an important economic damage, make among them a distinction according to the arising area and to the seriousness of their manifestations. They, later, describe corrective and prophylactic measures which in colo-rectal surgery ase campulsory assumptions for sepsis prevention. After relating their experience, Authors reaffirm short-term protocol validity and point out validity of alternation of large spectrum molecules in order to avoid possible arising of bacterial resistances.