Orwik

Laparoscopic enucleation of a jejunal mesenteric cyst: a case report.

Mesenteric cysts (MC) are a rare surgical condition occurring approximately in 1/200.000-350.000. The aetiology is unknown and the rarity of the tumor has led to confusion about their nature and classifi cation. They can be uni- or multi-locular, and... expand abstract are mostly benign. Approximately 830 cases have been reported in the literature and only four of them were found to be malignant. Cysts are usually diagnosed during routine abdominal examinations, they can present with various signs, such as acute abdominal pain, chronic abdominal pain, nausea and vomiting, or change in bowel habit. Although rare, shock due to rupture or bleeding of the cyst, intestinal obstruction secondary to external compression and volvulus or torsion of the cyst have been reported. Defi nitive treatment requires complete surgical resection of the cyst and is indicated when the lesion causes symptoms. We report a case of calcifi ed MC which was completely excised using the laparoscopic approach. collapse abstract

Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome in patients with liver disease. It was suggested that Bifidobacterium+fructo-oligosaccharides (FOS) may decrease blood and brain ammonia levels. AIM: The study was cond... expand abstractucted to compare the efficacy of Bifidobacterium+FOS and lactulose in patients with HE. METHODS: One hundred and twenty-five patients (35 hepatitis B virus infected, 70 hepatitis C virus infected and 20 cryptogenetic cirrhosis) were enrolled in the study. Patients were randomized either to a treatment for 60 days with Bifidobacterium and FOS (group A) or into-group receiving lactulose (group B) in double-blind. RESULTS: After 30 days of the study period, the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of Trail Making Test B (TMT B) (P<0.005), and a significant increase of Symbol Digit Modalities Test (P<0.001) and Block Design Test (P<0.001).After 60 days of the study period, the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of NH4 fasting HE1 (P<0.001), TMT A (P<0.05), TMT B (P<0.001), and a significant increase of Symbol Digit Modalities Test (P<0.001) and Block Design Test (P<0.001). CONCLUSION: The treatment with Bifidobacterium+FOS is an alternative to the use of lactulose in patients with cirrhosis, for its usefulness in reducing blood ammonia levels and improvement of psychometric tests. collapse abstract

l-Carnitine Supplementation to Diet: A New Tool in Treatment of Nonalcoholic Steatohepatitis-A Randomized and Controlled Clinical Trial.

OBJECTIVES:Nonalcoholic steatohepatitis (NASH) is a known metabolic disorder of the liver. No treatment has been conclusively shown to improve NASH or prevent disease progression. The function of L-carnitine to modulate lipid profile, glucose metabol... expand abstractism, oxidative stress, and inflammatory responses has been shown. The aim of this study was to evaluate the effects of L-carnitine's supplementation on regression of NASH.METHODS:In patients with NASH and control subjects, we randomly dispensed one 1-g L-carnitine tablet after breakfast plus diet and one 1 g tablet after dinner plus diet for 24 weeks or diet alone at the same dosage and regimen. We evaluated liver enzymes, lipid profile, fasting plasma glucose, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, homeostasis model assessment (HOMA)-IR, body mass index, and histological scores.RESULTS:At the end of the study, L-carnitine-treated patients showed significant improvements in the following parameters: aspartate aminotransferase (P=0.000), alanine aminotransferase (ALT) (P=0.000), gamma-glutamyl-transpeptidase (gamma-GT) (P=0.000), total cholesterol (P=0.000), low-density lipoprotein (LDL) (P=0.000), high-density lipoprotein (HDL) (P=0.000), triglycerides (P=0.000), glucose (P=0.000), HOMA-IR (P=0.000), CRP (P=0.000), TNF-alpha (P=0.000), and histological scores (P=0.000).CONCLUSIONS:L-carnitine supplementation to diet is useful for reducing TNF-alpha and CRP, and for improving liver function, glucose plasma level, lipid profile, HOMA-IR, and histological manifestations of NASH. collapse abstract

Activin A in asphyxiated full-term newborns with hypoxic ischemic encephalopathy.

Activin-A is a protein over-expressed and secreted by the brain after neuronal destruction. We evaluated whether serum activin-A increases in asphyxiated full-term newborns (AFTNs) at risk of hypoxic-ischemic-encephalopathy (HIE). 105 consecutive inf... expand abstractants (35 affected by perinatal asphyxia due to acute fetal distress; 70 healthy gestational-age matched newborns) underwent cranial assessment and neurologic examination at 12, 24 and 72 hours after birth and, on discharge from the hospital and; activin-A and monitoring laboratory variables assessment at birth. According to the occurrence of HIE within 7-days after birth, AFTNs were subdivided in Group A (n= 20; no/mild HIE with good prognosis) and Group B (n= 15; moderate/severe HIE with a greater risk of neurological handicap). Activin-A was significantly (P less than 0.0001) higher in Groups A and B than controls and highest (P less than 0.001) in Group B. At 0.66 ng/L activin-A achieved a sensitivity of 93.33 per cent and a specificity of 96.63 per cent, respectively, as HIE diagnostic test. These findings show that activin A increased in AFTNs with HIE before the appearance of related signs. collapse abstract

S100B protein and near infrared spectroscopy in preterm and term newborns.

Cerebral monitoring constitutes an emerging issue in perinatal medicine. Near Infrared Spectroscopy (NIRS) monitors brain oxygenation status in sick infants although data in healthy infants are lacking. The present study investigates whether NIRS par... expand abstractameters change according to gestational age and correlate with S100B protein. We recruited 64 healthy newborns (weeks' gestation: 30-42 wks) in which we performed in the first 6-hours after birth routine clinical, radiological and laboratory variables, cerebral oxygen saturation (rSO2), fractional cerebral tissue oxygen extraction (FTOE) values and S100B urine assessment. rSO2 and FTOE correlated (R=-0.73; R=0.51; P less than 0.01, for both) with gestational age. Highest rSO2 and the lowest FTOE peaks (P less than 0.001) were found at 30-33 wks. From 34 wks onwards, rSO2 progressively decreased and FTOE increased reaching their lower dip/peak (P less than 0.001) at 38-39 weeks. A significant correlation between S100B and NIRS parameters (rSO2: r=0.77; FTOE: r=-0.69; P less than 0.01) has been found. The present study shows that NIRS parameters and S100B protein correlation may be of help in brain function monitoring. collapse abstract

The aristaless (Arx) gene: one gene for many "interneuronopathies".

The ARX (Aristaless-related (X-linked) homeobox) gene is not only present in arthropods and their ancestors, but also in vertebrates including humans (ARX orthologs). The gene is composed of 5 coding exons and it is expressed predominantly in foetal ... expand abstractand adult brain and skeletal muscle. In this review we report on our experience and review the existing literature on the genotype and phenotype heterogeneity associated with ARX abnormalities in humans ranging from severe neuronal migration defects (e.g., lissencephaly), to mild forms of X-linked mental retardation without apparent brain abnormalities. The ARX-related disorders are reviewed focusing on their clinical features and on the role of the ARX gene. It has yet to be established whether the molecular defect alone could cause a given cerebral abnormality and/or malformation or an additional or related molecular or environmental event could contribute to a given phenotype in molecularly. collapse abstract

Biochemical markers of perinatal brain damage.

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-... expand abstractregulation leading to cell death and tissue damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia. To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, S100B, activin A, neuronal specific enolase (NSE), glial fibrillary acid protein (GFAP), in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia. collapse abstract

Biomarkers of myocardial injury after cardiac arrest or myocardial ischemia.

Outcomes of victims of cardiac arrest or acute myocardial ischemic events have improved with advances in medical therapy. Heart failure, however, remains a leading cause of morbidity and mortality after these conditions have occurred. Clinical featur... expand abstractes may be useful for predicting patients who are at risk of developing such complications, but they lack of sensitivity and specificity. Biomarkers have been therefore suggested as means to provide relevant prognostic information. The more commonly used biomarkers after cardiovascular ischemic events, including cardiac arrest, are creatin kinases and troponins. In addition, natriuretic peptides and C-reactive protein have gained great interest and now sufficient data has been collected such to justify their clinical applicability. Finally, several other novel biomarkers, to be used after resuscitation from cardiac arrest or more generally after a myocardial ischemic event, have been anticipated. Nevertheless, the "perfect" biomarker, able to provide diagnosis and prognosis with high sensitivity and specificity does not exit. A multimarker strategy that categorizes patients based on the number of elevated biomarkers at presentation is therefore suggested. collapse abstract

Genetic risk factors and candidate biomarkers for Alzheimer's disease.

Alzheimer's disease is a multifactorial and progressive neurodegenerative disease, extremely diffused and with an increasing prevalence worldwide. There is an urgent need for biomarkers to diagnose AD early in its course. Furthermore, accurate biomar... expand abstractkers would be able to determine the clinical efficacy of novel neuroprotective strategies. Although the heritability of late-onset AD is high, our knowledge of the underlying putative susceptibility genes remains incomplete and the only unequivocally established late-onset AD gene is APOE. Nevertheless a number of susceptibility loci seems to influence the pathogenesis of AD, and variations in numerous genes have been considered to be important in the risk for AD. Many advances have been made in identifying biochemical indices of brain dysfunction, measured in body fluids such as cerebrospinal fluid and plasma, with different methodological approaches. Although these biomarkers are promising, none of them can predict AD with 100% confidence to date. This review will elaborate on the available selection of genetic and biochemical biomarkers for AD, with a particular reference to those linked to inflammation and oxidative stress. collapse abstract

Clinical biomarkers in brain injury: a lesson from cardiac arrest.

Cardiac arrest (CA) is the primary cause of death in industrialized countries. Successful resuscitation rate is estimated of about 40%, but a good neurological outcome remains difficult to achieve. The majority of resuscitated victims suffers of a pa... expand abstractthophysiological entity termed as "post resuscitation disease". Today's efforts are mainly pointed to the chain of survival, often devoting less attention to post-resuscitation care. Resuscitated patients are often victims of nihilistic therapeutic approach, with clinicians failing to promptly institute strategies that mitigate the ischemia-reperfusion injury to vital organs. Only after 72 hours prognostication can be realistically attempted. Neurological evaluation relies on a combination of clinical, instrumental and laboratoristic parameters, since no one alone holds a specificity of 100%. Biochemical markers, such as neuron specific enolase and S-100b, may contribute to predict prognosis after CA. To the contrary, when used individually the necessary precision remains poorly characterized. Biochemical studies suffer from substantial methodological differences hampering attempts to summarize their findings. We review the information available on biochemical markers of brain damage for neurological prognostication after CA. collapse abstract

New markers of neonatal neurology.

Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain-blood barrier permeability modifications leading to cerebral vascular auto-regulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion are the main events i... expand abstractnvolved in vascular auto-regulation loss leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents, of calcium mediated effects could be responsible for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and damage. These phenomena represent a common repertoire in newborns complicated by perinatal acute or chronic hypoxia treated by risky procedures such as mechanical ventilation, nitric oxide supplementation, brain cooling, and extracorporeal membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period is crucial, as clinical symptoms and standard monitoring parameters may be silent at a time when brain damage is already occurring and the therapeutic window for pharmacological intervention is limited. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk newborns. The present review is aimed at investigating the role of biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein, in the cascade of events leading to I-R injury in newborns complicated by perinatal asphyxia. collapse abstract

Distal pancreatectomy with en bloc resection of the celiac axis for pancreatic adenocarcinoma.

Resection of celiac axis for gastric cancer was first performed by Appleby in 1953. Subsequently, Mayumi et al. and Kimura et al. adopted this approach for locally advanced adenocarcinoma of pancreatic body. We are here describing this technique in c... expand abstractase of adenocarcinoma of pancreatic body with infiltration of celiac axis achieving also gastric preservation. Our patient presented with diabetes, back pain and weight loss. CT scan showed a 3 cm mass in the body of pancreas infiltrating the origin of celiac axis, causing obstructive atrophy of pancreatic tail. Bilirubin, transaminases, amylase and tumoral markers were in the normal range with the exception of CEA (34 ng/ml) and chromogranin (30 IU/l). Vascular reconstruction imaging indicated the feasibility of the procedure. Under intraoperative ultrasound guidance we clamped the common hepatic artery in order to check the gastric and hepatic blood flow. We then performed a distal pancreasectomy and splenectomy with "en bloc" resection of celiac axis and regional lymphadenectomy. Appleby operation can increase the resectability of locally advanced cancer of the body and tail of the pancreas and offers not only a better life quality for patients but also perfect pain relief. This technique demands a multidisciplinary approach with careful pre and intra operative vascular evaluation, which is mandatory in assessing candidacy for this procedure. collapse abstract

Schisandrin B stimulates a cytoprotective response in rat liver exposed to mercuric chloride.

Mercury represents an ubiquitous environmental toxic metal. Heat shock proteins (HSP) and metallothioneins (MTs) help to protect cells against metal toxicity. Schisandrin B (Sch B), a lignoid from Schisandra chinensis, has been successfully used to t... expand abstractreat hepatitis, but its effect against mercury hepatotoxicity remains unknown. We analyzed whether Sch B could protect rat liver against mercuric chloride (HgCl2) intake by analyzing stress proteins and histopathological changes. Wistar rats were administered Sch B (10mg/kg/day by gavage) or vehicle (olive oil) for 10 days. A subset of each group also received low-dose HgCl2 (0.1mg/kg/day) for 3 days on days 8-10. Another group received Sch B for 10 days with a single high dose of HgCl2 (1mg/kg intraperitoneally) on day 10. In rats treated with Sch B and HgCl2, HSP72, HSP25 and MTs were overexpressed in liver zones 1 and 3 irrespective of HgCl2 dosing schedules. Furthermore Sch B alone induced perinuclear rough endoplasmic reticulum alignment and if associated to HgCl2, increased mitochondrial density and dense bodies, all signs of intense detoxification machinery. Taking together these data suggest that dietary Sch B counteracts HgCl2 hepatotoxicity in the rat by stimulating chaperones responsible for anabolic activity. collapse abstract

Prolactin induces chitotriosidase expression in human macrophages through PTK, PI3-K, and MAPK pathways.

We previously reported that prolactin (PRL) induces chitotriosidase (CHIT-1) mRNA expression in human macrophages. In this investigation we determined the signaling pathways involved in CHIT-1 induction in response to PRL. The CHIT-1 induction PRL-me... expand abstractdiated was reduced by wortmannin and LY-294002, inhibitors of phosphatidylinositol 3-kinase (PI3-K) and by genistein an inhibitor of protein tyrosine kinase (PTK). Pre-treatment of macrophages with SB203580, a specific inhibitor of the mitogen-activated kinases (MAPK) p38, or with U0126, an inhibitor of MAPK p44/42, prevented both basal and exogenous PRL-mediated CHIT-1 expression. No significant effects on CHIT-1 induction PRL-mediated were observed with a protein kinase C inhibitor (PKC), rottlerin, or with an Src inhibitor, PP2, or with JAK2 inhibitor, AG490. In addition, PRL induced a phosphorylation of AKT that was prevented both by the two MAPK inhibitors SB203580 and U0126 and by the PI3-K inhibitors wortmannin and LY-294002. In conclusion, our results indicate that PRL up-regulated CHIT-1 expression via PTK, PI3-K, MAPK, and signaling transduction components. collapse abstract

Near Infrared Spectroscopy in healthy preterm and term newborns: correlation with gestational age and standard monitoring parameters.

Near Infrared Spectroscopy (NIRS) is an emerging technique for brain oxygenation monitoring in newborns complicated by acute and chronic hypoxia. However, data regarding cerebral oxygenation normal values are still lacking and matter of debate. There... expand abstractfore, we investigate whether NIRS parameters in healthy preterm/term infants are gestational age and delivery modalities dependent and correlate with standard monitoring parameters. From January to December 2007, 100 healthy newborns with gestational age from 30 to 42 weeks' gestation were evaluated. Routine laboratory variables, daily clinical and neurological evaluation and ultrasound imaging were performed. The regional cerebral oxygen saturation (rSO2) and fractional cerebral tissue oxygen extraction (FTOE) were measured by NIRS in the first 6-hours after birth. Data were recorded by MetaVision ICU X-Edition software and analyzed by SPSS statistical package. rSO2 and FTOE correlated (R=-0.77; R=0.41; P<0.01, for both) with gestational age. Highest rSO2 and the lowest FTOE peaks (P<0.001, for all) were found at 30-33 wks when compared with other monitoring periods. From 34 wks onwards, rSO2 progressively decreased and FTOE increased reaching their lower dip/peak (P<0.001, for all) at 38-39 weeks. rSO2 and FTOE values were significantly different (P<0.05, for both) between preterm and term newborns when corrected for delivery modality. rSO2 correlated (P<0.001 for all) with heart (r=0.63), respiratory (r=-0.58) rate, and with arterial oxygen saturation (r=0.65). In conclusion, in the first 6-hours after birth cerebral oxygenation in healthy newborns is gestational age-dependent and correlated with routine parameters. NIRS reference curve could be particularly useful in sick newborns brain monitoring. collapse abstract

Effects of simvastatin and carnitine versus simvastatin on lipoprotein(a) and apoprotein(a) in type 2 diabetes mellitus.

AIM: The aim of the present study was to compare the effects of simvastatin and L-carnitine coadministration versus simvastatin monotherapy on lipid profile, lipoprotein(a) (Lp(a)) and apoprotein(a) (Apo(a)) levels in type II diabetic patients. PATIE... expand abstractNTS/METHODS: In this double-blind, randomized clinical trial, 75 patients were assigned to one of two treatment groups for 4 months. Group A received simvastatin monotherapy; group B received L-carnitine and simvastatin. The following variables were assessed at baseline, after washout and at 1, 2, 3 and 4 months of treatment: body mass index, fasting plasma glucose, glycated hemoglobin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, Apolipoprotein A1, Apo B, lipoprotein(a) and apoprotein(a). RESULTS: At the end of treatment in the carnitine and simvastatin combined group compared with the simvastatin alone group, we observed a significant decrease in glycemia (p < 0.001), triglycerides (p < 0.001), Apo B (p < 0.05), Lp(a) (p < 0.05), apo(a) (p < 0.05), while HDL significantly increased (p < 0.05). CONCLUSIONS: The coadministration of carnitine and simvastatin resulted in a significant reduction in Lp(a) and apo(a) and may represent a new therapeutic option in reducing plasma Lp(a) levels, LDL cholesterol and Apo B100. collapse abstract

Effect of L-carnitine on the size of low-density lipoprotein particles in type 2 diabetes mellitus patients treated with simvastatin.

Therapeutic modulation of low-density lipoprotein (LDL) size could be of benefit in reducing the risk of cardiovascular events in diabetic patients. This study evaluated the efficacy of L-carnitine on the size of LDL particles in type 2 diabetes mell... expand abstractitus patients treated with simvastatin. Eighty diabetic patients were randomly assigned to 1 of 2 treatment groups for 3 months. The 2 groups received either simvastatin monotherapy 20 mg (n = 40) or L-carnitine 2 g/d and simvastatin 20 mg (n = 40). The following variables were assessed at baseline; after washout; and at 1, 2, and 3 months of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, LDL subclasses, LDL size, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1, and apolipoprotein B-100. After 12 weeks, comparing the 2 groups, we observed a decrease in fasting plasma glucose (1.45 vs 0.61 mmol/L, P < .001) and an increase in glycosylated hemoglobin (0.2% vs 0.4%, P < .05). Moreover, there was a decrease in total cholesterol (2.07 vs 1.45 mmol/L, P < .001), LDL (1.65 vs 1.29 mmol/L, P < .001), triglycerides (1.36 vs 0.41 mmol/L, P < .001), apo B-100 (49 vs 9 g/L, P < .001), and small-sized LDL proportion (10.8% vs 4.9%, P < .001), whereas LDL particle size increased (6 vs 3 A, P < .001) and HDL increased (0.2 vs 0.11 mmol/L, P < .001). We observed that patients treated with carnitine and simvastatin showed a reduction in small-sized LDL proportion and an increase in LDL particle size. collapse abstract

Symptomatic hypocalcemia in an epileptic child treated with valproic acid plus lamotrigine: a case report.

INTRODUCTION: An epileptic child had been long treated with valproic acid and lamotrigine. After a few years of treatment, he manifested severe clinical signs of hypocalcemia. We retain that valproic acid could have caused such metabolic dysfunction.... expand abstract CASE PRESENTATION: We report here the involvement of valproic acid in symptomatic hypocalcemia in an 11-year-old epileptic white patient in treatment with valproic acid and lamotrigine. During the treatment the patient developed hypocalcemia associated with high plasma levels of valproic acid, parathyroid hormone and alkaline phosphatase, indicating increased bone turnover. Plasma levels of Vitamin D were normal. Plasma calcium values significantly correlated with valproic acid haematic levels; reduction of valproic acid dose was accompanied by prompt normalization of calcemia. The specific mechanism through which valproic acid causes hypocalcemia is unknown, although the relationship between valproic acid dose and haematic levels of calcium appears very likely. CONCLUSIONS: It seems necessary, during long term therapy with valproic acid, to monitor plasma calcium and alkaline phosphatase plasma levels. Also, these patients should undergo treatment and perhaps prescribe vitamin D and calcium treatment. collapse abstract

Increased maternalfetal blood S100B levels following systemic endotoxin administration and periventricular white matter injury in preterm fetal sheep.

OBJECTIVE: Intrauterine infection is suggested to cause perinatal brain white matter injury. In the current study, we evaluated whether S100B, a brain damage marker, may be also assessed in maternal bloodstream after white matter injury induced by fe... expand abstracttal intravenous application of lypopolisaccharide (LPS) endotoxin. METHODS: Fourteen fetal sheeps were chronically catheterized at a mean gestational age of 107 days. Three days after surgery, fetuses (n = 7) received 500 ng of LPS or 2 mL 0.9% saline (n = 7) intravenously (IV). Lypopolisaccharide and placebo groups were monitored by continuous hemodynamic data recordings and at 6 predetermined time points (control value; 3, 6, 24, 48, and 72 hours after LPS/placebo administration) blood was drawn for laboratory parameters and S100B assessment. Brain damage was evaluated by light microscopy after Klüver-Barrera staining. Selected areas of the periventricular white matter were also examined by electron microscopy. RESULTS: White matter injury was detected in all LPS-treated fetuses, whereas no abnormalities were seen in control animals or in LPS-treated mothers. Maternal and fetal S100B protein levels were significantly higher in the LPS group than in the control group at all monitoring time points (P < .001). The highest fetal-maternal S100B levels were observed at 3-hour time-point (P < .001). CONCLUSIONS: We found that S100B protein is increased in the maternal district in presence of fetal periventricular brain white matter injury induced by endotoxin. The present data offer additional support for S100B assessment in the maternal circulation in pregnancies complicated by intrauterine infection at risk of white matter injury. collapse abstract

Light scattering study of natural DNAs over a wide range of molecular weights: Evidence for compaction of the large molecules.

This work reports light scattering measurements on DNA in aqueous solutions (100mM NaCl, 1mM EDTA and 10mM Tris-HCl buffer, pH 7.8) over a wide range of molecular weights (10(2)-10(5) base pairs) and shows that, in the above standard solvent, shorter... expand abstract chains (<10(4) base pairs) behave as a "wormlike chain" and their diffusion coefficients as obtained by dynamic light scattering measurements, confirm the prediction of standard wormlike model, whilst longer chains (>10(4) base pairs) behave in a different manner. Dynamic and static light scattering and SEM analysis indicate that DNA molecules 10(5) base pairs long, condense into compact structures in our solvent conditions. Calculations done using a wormlike model are also presented and discussed in comparison both to our experimental data and to other data reported in the literature. collapse abstract

Antioxidant properties of anesthetics: the biochemist, the surgeon and the anesthetist.

General anesthesia can impair immunological defense mechanisms while inducing an inflammatory reaction. Generalized inflammatory reactions involve leucocytes which in turn release inflammatory mediators and free oxygen radicals. General anesthetics i... expand abstractnclude a series of gaseous and intravenous sedative-hypnotic agents indicated for induction and maintenance of general anesthesia as well as for sedation of intubated, mechanically ventilated adults in intensive care units (ICU). Some anesthetics, such as propofol, are characterized by a phenolic structure similar to that of alpha-tocopherol, and exhibit antioxidant properties that have been demonstrated both in vitro and in vivo. Similarly, other anesthetics show antioxidant and protective roles but this mechanism is to be related to their ability to induce antioxidant enzyme (i.e., heme oxygenase-1). The aim of the present review is to evaluate the antioxidant properties of anesthetics in various experimental models and if they may be considered efficient therapeutic tools in counteracting oxidative stress during general anesthesia and sedation in ICU. collapse abstract

Endothelial protective effects of anthocyanins: the underestimated role of their metabolites.

Circulating biochemical markers of brain damage in infants complicated by ischemia reperfusion injury.

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-... expand abstractregulation leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents of calcium mediated effects could be responsible for reperfusion injury, which, in turns, leads to cerebral hemorrhage and damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia or cardiovascular disorders treated by risky procedures such as open heart surgery and cardiopulmonary by-pass (CPB). To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein; neuronal specific enolase (NSE), a dimeric isoenzyme; glial fibrillary acid protein (GFAP), a astroglial protein, in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia or cardiovascular disorders requiring risky therapeutic strategies such as CPB and/or extracorporeal membrane oxygenation. collapse abstract

Beneficial effects of rutin and L-arginine coadministration in a rat model of liver ischemia-reperfusion injury.

Reperfusion following liver ischemia results in oxidative stress leading to liver injury. The aim of this study was to investigate the combined effects of two antioxidant agents, rutin and L-arginine, in rat liver ischemia-reperfusion (I/R). Male Wis... expand abstracttar rats were divided into five groups: 1) sham operated, 2) I/R, 3) I/R+rutin, 4) I/R+L-arginine, and 5) I/R+rutin+L-arginine. Plasmatic and hepatic levels of alanine transaminase (ALT), aspartate transaminase (AST), lipid peroxides (LOOH), and thiol groups (RSH) were examined, as well as DNA fragmentation and liver histopathology. Furthermore, to elucidate the pathophysiological processes involved in the antioxidant mechanism(s) of rutin and L-arginine, we assessed the expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) isoforms and heme oxygenase-1 (HO-1), both playing key roles in the biochemical cascade of liver injury. Significant increase in plasmatic ALT and AST activities were observed in untreated I/R rats compared with sham-operated animals, whereas treatment with rutin or L-arginine in I/R rats reduced hepatic damage. Interestingly, combined therapy with rutin and L-arginine resulted in a further reduction of plasmatic ALT and AST activities compared with rutin or L-arginine alone. These results were further confirmed by the analysis of DNA fragmentation, LOOH, RSH groups, and liver histopathology, which showed the highest protective effects following the coadministration of rutin and L-arginine. Finally, the combined therapy protocol resulted in a significant induction of liver HO-1 and a concomitant reduction of iNOS expression that may both be responsible for the beneficial effects of the proposed pharmacological protocol. collapse abstract

Effect of ischemia-reperfusion on renal expression and activity of N(G)-N(G)-dimethylarginine dimethylaminohydrolases.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. It is degraded by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). METHODS: Rats (n = 50) underwent to 45 min of renal ischemia followed by ... expand abstract30 min, 1 h, and 3 h of reperfusion. Expression of endothelial nitric oxide synthase, inducible nitric oxide synthase, DDAH-1, DDAH-2, renal DDAH activity, plasma NO2(-)/NO3(-), and ADMA levels were evaluated. RESULTS: Inducible nitric oxide synthase expression increased, as confirmed by both plasma (11.89 +/- 1.02, 15.56 +/- 0.93, 11.82 +/- 0.86, 35.05 +/- 1.28, and 43.89 +/- 1.63 nmol/ml in the control, ischemic, 30-min, 1-h, and 3-h groups, respectively) and renal (4.81 +/- 0.4, 4.85 +/- 1, 9.42 +/- 0.7, 15.42 +/- 0.85, and 22.03 +/- 1.11 nmol/mg protein) formations of NO2(-)/NO3(-). DDAH-1 expression decreased after reperfusion, whereas DDAH-2 increased after 30 min, returning to basal levels after 3 h. Total DDAH activity was reduced during all times of reperfusion. Both plasma (0.41 +/- 0.03, 0.43 +/- 0.05, 0.62 +/- 0.02, 0.71 +/- 0.02, and 0.41 +/- 0.01 nmol/ml in the control, ischemic, 30-min, 1-h, and 3-h groups, respectively) and renal (1.51 +/- 0.01, 1.5 +/- 0.01, 1.53 +/- 0.01, 2.52 +/- 0.04, and 4.48 +/- 0.03 nmol/mg protein in the control, ischemic, 30-min, 1-h, and 3-h groups, respectively) concentrations of ADMA increased. CONCLUSIONS: Results suggest that ischemia-reperfusion injury leads to reduced DDAH activity and modification of different DDAH isoform expression, thus leading to increased ADMA levels, which may lead to increased cardiovascular risk. collapse abstract