Effect of hepatitis B virus on steatosis in hepatitis C virus co-infected subjects: A multi-centre study and systematic review.

It remains unclear whether hepatitis B virus (HBV) infection may modify the severity of viral steatosis in patients coinfected with chronic hepatitis C virus (HCV). We examined the influence of coinfection with HBV on prevalence of steatosis in chronic hepatitis C in a multi-centre cohort of HBV-HCV subjects, and by performing a systematic review and meta-analysis of the literature. We centrally and blindly assessed steatosis prevalence and severity in a cohort of HBV-HCV coinfected subjects compared to HCV and HBV monoinfected controls and we performed a systematic review of studies addressing the prevalence of steatosis in HBV-HCV subjects compared to HCV controls. In the clinical cohort, we included 85 HBV-HCV, 69 HBV and 112 HCV subjects from 16 international centres. There was no significant difference in steatosis prevalence between the HBV-HCV and the HCV groups (33% vs 45%, P = .11). In subgroup analysis, lean HBV-HCV subjects with detectable HBV DNA had less steatosis than lean HCV subjects matched for HCV viremia (15% vs 45%, P = .02). Our literature search identified 5 additional studies included in a systematic review. Overall, prevalence of steatosis > 5% was similar in HBV-HCV infection compared to HCV (pooled odds ratio [OR] 0.91, 95% CI 0.53-1.6) although there was significant heterogeneity (I2 69%, P = .007). In conclusion, although the prevalence of steatosis is similar in HBV-HCV compared to HCV subjects, our analysis suggests that there may be an inhibitory effect of HCV-induced steatogenesis by HBV in certain subgroups of patients.

Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy.

Anaemia frequently complicates peginterferon/ribavirin therapy for chronic hepatitis C infection. Better prediction of anaemia, ribavirin dose reduction or erythropoietin (EPO) need, may enhance patient management. Inosine triphosphatase (ITPA) genetic variants are associated with ribavirin-induced anaemia and dose reduction; however, their impact in real-life clinic patient cohorts remains to be defined. We studied 193 clinic patients with chronic hepatitis C infection of mixed viral genotype (genotype 1/4 n = 123, genotype 2/3, n = 70) treated with peginterferon/ribavirin. Patients were genotyped for ITPA polymorphisms rs1127354 and rs7270101 using Taqman primers. Hardy-Weinberg equilibrium was present. Estimated ITPA deficiency was graded on severity (0-3, no deficiency/mild/moderate/severe, n = 126/40/24/3, respectively). Multivariable models tested the association with anaemia at 4 weeks of treatment [including decline in haemoglobin (g/dL); haemoglobin <10 g/dL and haemoglobin decline >3 g/dL]; ribavirin dose reduction and EPO use and explored sustained viral response (SVR) to peginterferon/ribavirin. More severe ITPA deficiency was associated with less reduction in haemoglobin level (P <0.001; R(2) = 0.34), less ribavirin dose reduction (OR 0.42; (95% CI = 0.23-0.77); P = 0.005) and less EPO use [OR 0.53; (0.30-0.94); P = 0.029]. ITPA deficiency was associated with SVR [OR: 1.70; (1.02-2.83); P = 0.041] independently of clinical covariates (adjusted R(2) = 0.31). In this clinical cohort, ITPA deficiency helped predict the risk of on-treatment anaemia, ribavirin dose reduction, need for EPO support and was associated with SVR. For patients on HCV regimens including peginterferon/ribavirin, testing for ITPA deficiency may have clinical utility.

A survey of dioxins (PCDDs and PCDFs) and dioxin-like PCBs in sheep and goat milk from Campania, Italy.

In 2008, after the crisis of buffalo dairy fields in Campania, Italy, an assessment of the contamination of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) was also necessary for other animal species bred in the region. The contents of PCDDs, polychlorinated dibenzofurans (PCDFs), and dl-PCBs were determined by high-resolution gas chromatography/mass spectrometry (HR-GC/MS) (according to USEPA method 1613) in 69 sheep and goat milk samples from 63 farms. In eleven samples from six sheep farms, the PCDD/Fs levels exceeded the maximum limit of 3.0 pg g(-1) fat established by the European Commission, in particular the concentrations ranged between 3.89 and 12.90 pg g(-1) fat. Statistical treatment of the results for the congener profiles of the non-compliant and compliant samples has been used to identify the sources of contamination.

Levels and congener profiles of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and dioxin-like polychlorinated biphenyls in cow's milk collected in Campania, Italy.

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and certain dioxin-like polychlorinated biphenyls (dl-PCBs) are a family of chemically-related lipophilic compounds characterized by similar toxicity. Due to their properties they are universally distributed in the environment and classified as persistent organic pollutants (POPs). From most of studies carried out to evaluate human dietary intake, milk and dairy products result as a major contributors of PCDD/Fs uptake. Of course the main source of milk contamination is animal feeds. Lactating ruminants, cows included, transfer these compounds to the food chain by ingestion of contaminated vegetables or soil. Their resistance to degradation and a high lipophilicity means that PCDD/Fs and dl-PCBs may be accumulated into fat tissues from which they are transferred to milk during lactation period. Seventy-nine cows milk samples, collected in the monitoring plan 2008, were analyzed for PCDD/Fs and dl-PCBs. Eleven milk samples were non-compliant corresponding to five breeding livestock located in Caserta province. The distribution of PCDD/Fs and dl-PCBs congeners in these samples was examined in order to determine the likely sources of dioxins. The results show that the congener profile is characterized by a prevalence of PCDFs in respect of PCDDs, that represents the typical pattern of thermal origin contamination.

[Hepatic haemorrhage in pregnancy: a case report]. / Emorragia epatica in gravidanza: caso clinico.

Spontaneous hepatic haemorrhage in pregnancy (SHHP) is a rare event (1 woman out of 15,000). It is generally considered as an advanced state of the microangiopathic hemolytic anemia (HELLP, Hemolysis, Elevated Liver enzyme levels, Low Platelet count). Furthermore, the HELLP is considered as a different form of preeclampsia. The patient, a 33-year-old-woman at 30 weeks' gestation, was admitted to hospital for preeclampsia, underwent an emergency Stark caesarean section with the extraction of an alive foetus and evidence of massive intraperitonal haemorrhage from a large hepatic haematoma. A haemostasis with gauzes of Surgicel was performed, with consequent arrest of the haemorrhage. After approximately 6 hours, a recurrence of the intraperitonal haemorrhage led to a new surgical intervention with hepatic packing with gauzes. After 4 days the patient died. The etiopathogenesis of disease is uncertain, both foetal and maternal mortality are high, and the slight number of reported cases (27) of SPPH from HELLP in international literature offer elements for debate. The following points have been put forward: 1. the monitoring of the counts of the platelets represent the only valid predictive test of HELLP. These concerned women in the third trimester of pregnancy, especially those with a history of preeclampsia; 2. the treatment must be immediate, intensive and multidisciplinary, the plasmapheresis has remarkably improved the prognosis; 3. surgical treatment performed in order to control the SPPH makes use of packing, embolization and/or fastening of the common hepatic artery and, in extreme cases, total hepatectomy with transplantation. The Authors believe it is useful to suggest a national epidemiological research in order to estimate the real incidence of the syndrome in Italy and to establish the guidelines for the medico-surgical treatment.

[Surgical complications for gastric and small bowel metastases due to primary lung carcinoma]. / Complicanze chirurgiche per metastasi gastriche e digiuno-ileali da carcinoma primitivo polmonare.

Lung carcinoma is the first cause of death for tumors; in Italy there are from 35,000 to 40,000 new cases a year, with a global survival to 5 years from the diagnosis in 13% of cases. The gastric and small bowel metastases are rare, respectively 0.4% and 1.1% and the cases reported in the literature are rare. There is often a poor symptomatology and diagnosis is usually based on post-mortem examination. Yet, sometimes, the first and only demonstration of the secondary illness is a surgical complication, whether it be a haemorrhage, a perforation or an occlusion. The authors report their experience, from April 1999 to March 2003, of 3 cases of small bowel metastases, presented in 1 case with a perforation and in 2 cases with an occlusion and of 1 case of gastric metastasis, which presented with a haemorrhage. These patients were treated by emergency surgery, with 1 case only of postoperative mortality. The 1st patient died 6 months after surgery, and the 2nd patient 6 days after, the 3rd patient 4 months after the 1st operation and the 4th patient is still in follow-up after 6 months. The authors present a review of the literature and some considerations of diagnosis and surgical treatment.

[The meshes of polypropylene in emergency surgery for strangulated hernias and incisional hernias]. / La protesi di polipropilene in chirurgia d'urgenza per laparoceli ed ernie strozzate.

INTRODUCTION: The Authors present their experience on the use of meshes of polypropylene in septic surgery of the abdominal wall defects. MATERIALS AND METHODS: From April 1999 to October 2003, 23 patients underwent intestinal resection (20 small intestine, 3 large intestine) for ischemic necrosis strangulation caused by defects in the abdominal wall (inguinal hernia 8, crural hernia 4, umbilical hernia 3, post-incisional hernia under umbilicus 3, post-incisional hernia epigastric 3, giant post-incisional hernia 2). RESULTS: No patient died and the removal of the mesh was never required in cases of infection of the surgical wound; 2 surgical wounds festered, with the reopening of the cutaneous wound and showing of the prosthesis, 5 hygromas were all treated in a conservative way. DISCUSSION: The macroporous structure of the meshes of polypropylene, with pores of diameter larger than 70 microns, allows contact among the bacteria, which measure one micron in diameter, and the cells of the immune system, granulocytes and macrophages, with a diameter of 15-20 microns, allowing the recovery from infections, and determining an high resistance rate to infections. CONCLUSIONS: Polypropylene prostheses, thanks to their macroporous structure, are sufficiently resistant to infections and therefore may be safely used in the surgery of the defects of the abdominal wall, when, following ischemic necrosis, an intestinal resection is necessary.

[Emergency surgery for neoplastic left colon obstruction: resection and primary anastomosis (RPA) versus Hartmann resection (HR)]. / Chirurgia d'urgenza per occlusione neoplastica del colon sinistro: resezione ed anastomosi primaria (RPA) versus resezione secondo Hartmann (HR).

UNLABELLED: This retrospective study compares: hospitalization time, morbidity and mortality (patients operated for neoplastic occlusion of the left colon in emergency, without perforation), considering hanestesiologic risk and surgical technique (RPA versus RH). MATERIALS AND METHODS: From April 1999 to February 2003 the Emergency Surgery of AORN of Caserta has operated, in urgency, 60 neoplastic patients with left colon occlusion realizing: 46 (76.5%) RPA [36 ASA < or = III, low hanestesiologic risk (LAR), 10 ASA = or > IV high hanestesiologic risk (HAR)], 12 (20%) RH (2 LAR and 10 HAR) 2 (3.5%) palliative colostomics. RESULTS: 36 LAR patients with RPA had 5% of specific complications and 5% of medical complications. 2 LAR patients with R-H: no complication. 10 HAR patient with RPA brought 10% of specific complications and 10% of medical complications. 10 HAR patients with RH had 20% of specific complications and 10% of general complications. The middle hospitalization of LAR patients with RPA was 11 days versus 9 days of RH pz. (equal hanestesiologic risk ). The HAR pz., treated with RPA, had as middle hospitalization 15 ggs in comparison to the 9 ggs of the HRA pz. treated with RH. MORTALITY: 1/36 for LAR pz. with RPA (3%), and 0/0 for LAR pz. with RH; 1/10 for HAR pz, with RPA (10%) and 1/10 for HAR pz. with RH (10%). CONCLUSIONS: Resection and primary anastomosis, (correct indications and expert surgeon), gives prevalence of complications and mortality similar to the repeated surgical procedure, a better life quality, but an higher number of post-operating hospitalisation days.

[Intraperitoneal hemorrhage from rupture of an aneurysm of splenic artery: case report and literature review]. / Emoperitoneo da fissurazione di aneurisma dell'arteria splenica: case report e revisione della letteratura.

Splenic artery aneurysm presented with rupture is an unusual and potentially deadly reason of intraperitoneal hemorrhage. There are a lot of pathogenetic hypothesis; timing according to disease severity and surgical choices aren't definitely codified authors present one patient with hemoperitoneum for ruptured splenic artery aneurysm affected by chronic lymphatic leukaemia too and review international literature; they underline pathogenesis, symptoms, preoperative investigations and therapy. Degeneration of the media, atherosclerotic changes and high blood flow due to pregnancy and portal hypertension could be the main pathogenetic factors. Ultrasonography is the first investigation we have to practice if we suspect hemoperitoneum. We can practice computed tomography and angiography too if cardiovascular condition are good. Rupture showing acute abdominal pain and cardiovascular collapse suggest strongly urgent operation. The choice of operation is determined by location of the aneurysm. When located in the distal third of the splenic artery, the aneurysm is resected with spleen; alternatively, when it is located in prossimal third we can perform conservative operation.

Increased vascular endothelial growth factor mRNA expression in the heart of streptozotocin-induced diabetic rats.

The aim of the present study was to evaluate vascular endothelial growth factor (VEGF), fms-like tyrosine kinase 1 (flt-1), and fetal liver kinase (flk-1) expression in the heart of experimental diabetic rats. Ten young adult male Wistar rats (5 streptozotocin [STZ]-induced diabetic rats, without insulin treatment, and 5 controls) were studied. Ninety days after the induction of diabetes, semiquantitative reverse transcription (RT)-polymerase chain reaction (PCR) coamplification of VEGF/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) transcription was performed. RT-PCR was also performed for VEGF receptors flk-1 and flt-1. VEGF mRNA expression, at 234 bp, was detectable in the heart of the rats and was significantly higher in those with diabetes. Densitometric analysis of PCR products showed that VEGF mRNA levels were meanly 4.8-fold higher in STZ-induced diabetic rats than controls (VEGF/GAPDH densitometric ratio, 3.46 +/- 0.20 v 0.74 +/- 0.10, P <.001). No significant difference was found in flt-1 and flk-1 amplification products between STZ-induced diabetic rats and controls (flt-1/GAPDH densitometric ratio, 0.58 +/- 0.01 v 0.64 +/- 0.05, P>.1; flk-1/GAPDH densitometric ratio, 0.66 +/- 0.10 v 0.7 +/- 0.06, P >.2). The increase in VEGF mRNA expression observed in this experimental diabetic model is in contrast with the typical impairment in collateral vessels of diabetic hearts. This apparent discrepancy might be explained by a resistance of cardiac tissue to VEGF. The lack of mRNA flt-1 and flk-1 overexpression in diabetic hearts could be one of the mechanisms for this resistance.

[Pica: a clinical case and therapeutic problems]. / Il picacismo: caso clinico e problematiche terapeutiche.

Pica is a psychotic disorder characterized by compulsive ingestion of nonfood substances; the primary treatment is the prevention with antipsychotic therapy. When the patient ingests foreign body, endoscopical removal is recommended. Surgical treatment is necessary when an acute abdomen is present, with intestinal occlusion and/or bowel perforation. The Authors report a peculiar case of pica, and analyse the problems of organization and assistance, besides surgical approach, also on the base of international literature.

[Peutz-Jeghers syndrome: case report and update on diagnosis and treatment]. / Sindrome di Peutz-Jeghers. Caso clinico ed attualità diagnostico-terapeutiche.

Peutz-Jeghers syndrome is a rare autosomal dominantly inherited condition with an incidence of 1/120.000 liveborns, characterized by the presence of hamartomatous gastrointestinal polyps and mucocutaneous pigmentation. This syndrome predisposes to various clinical problems such as intussusception and cancer development in different loci (gastrointestinal tract, breast and ovary). For this reason, PJS patients should undergo a surveillance protocol of the genital and gastrointestinal apparatus. Therefore, the early diagnosis of PJS in at-risk family members is very important in preventing cancer development. Germline mutations within the LKB1 or Serine Threonine Kinase (STK11) gene, located on chromosome 19p13.3, are responsible for most cases of PJS so far studied. The existence of a second locus is suspected on chromosome 19q13.4 in a minority of families. The LKB1 gene, recently cloned, encodes the Serine Threonine Kinase LKB1 and is ubiquitously expressed. The identification of the disease-causing mutation in each family makes it possible to perform a presymptomatic diagnosis; therefore, only the mutation carriers will undergo the clinical surveillance program. In this paper, the case of a PJS patient who has been surgically treated is presented. The DNA screening of the LKB1 gene in this patient has led to the identification of the causing mutation. A critical review of the literature and is also presented as well as the proposal to establish an Italian Registry of PJS.

Mechanisms of nitric oxide-induced cytotoxicity in normal human hepatocytes.

Chronic exposure of hepatocytes to reactive nitrogen species (RNS) following liver injury and inflammation leads not only to functional and morphological alterations in the liver but also to degenerative liver diseases and hepatocellular carcinoma. Previously, we showed that S-nitroso-N-acetylpenicillamine-amine (SNAP), which generates nitric oxide, and 3-morpholinosydnonimine (Sin-1), which generates equal molar concentrations of superoxide and nitric oxide resulting in peroxynitrite production, exhibited different levels of cytotoxicity to normal human hepatocytes in culture. The aim of the present study was to elucidate some of the molecular and cellular pathways leading to hepatocyte cell death induced by RNS. Following treatment of the hepatocytes with SNAP or Sin-1, gene-specific DNA damage was measured in mtDNA and a hprt gene fragment using a quantitative Southern blot analysis. Both agents induced dose-dependent increases in DNA damage that was alkaline labile, but not sensitive to both formamidopyrimidine-DNA glycosylase (fpg) and endonuclease III, which recognize 8-oxoguanine, thymine glycol, and other oxidized pyrimidines. DNA damage was two- to fivefold greater in mtDNA than in the hprt gene fragment. There was a persistent and marked increase in DNA damage posttreatment that appeared to arise from the disruption of electron transport in the mitochondria, generating reactive species that saturated the repair system. DNA damage induced by Sin-1 and SNAP led to cell-cycle arrest in the S-phase, growth inhibition, and apoptosis. The data support the hypothesis that the functional and morphological changes observed in liver following chronic exposure to RNS are, in part, the result of persistent mitochondrial and nuclear DNA damage.

Modulation of Ki67, p53 and RARbeta expression in normal, premalignant and malignant human oral epithelial cells by chemopreventive agents.

BACKGROUND: Aberrant expression of Ki67, p53 and RARbeta are characteristic of many tumor types including those of the oral cavity. Chemopreventive agents may act by modulating their expression to more normal levels. MATERIALS AND METHODS: The effects of 21 chemopreventive agents on the expression of Ki67, p53 and RARbeta were determined using a human in vitro model of normal, premalignant and malignant oral epithelial cell lines. RESULTS: Ki67 and mutant p53 (mtp53) were overexpressed in both the premalignant and malignant cell lines, whereas expression of RARbeta was high in the normal, low in the premalignant and not detectable in the malignant cell lines. Most of the agents selectively inhibited the expression of Ki67 in the premalignant and malignant cell lines. Eight of the 21 agents increased, while four agents decreased, the levels of mtp53 protein in the premalignant cell line. In the malignant cell line, five of the agents increased, while ten agents decreased mtp53 protein levels. The agents increased RARbeta expression to near normal levels in the premalignant cell line. CONCLUSION: The data suggest that the suppression of Ki67 and mtp53 are good indicators of the effectiveness of agents in premalignant and malignant oral cells, whereas the enhancement of RARbeta is a measure of effectiveness in premalignant oral cells.

Differential response of normal, premalignant and malignant human oral epithelial cells to growth inhibition by chemopreventive agents.

Squamous cell carcinoma (SCC) of the oral cavity is a multistep process, progressing through a series of discrete, irreversible and complementary alterations in genes that control cell growth, death, and differentiation. In the premalignant state, the oral mucosa progresses through various grades of epithelial dysplasia, with the potential to convert to SCC. Chemopreventive strategies are designed to suppress, reverse, or prevent the formation of premalignant lesions and their subsequent progression to SCC. In the present study, we determined the growth inhibitory effect of 21 chemopreventive agents in a cell culture model using normal, premalignant, and malignant human oral mucosal cell lines. There were significant differences in the growth inhibitory responses of these cell lines to selected retinoids and non-retinoid analogs. Among the retinoids tested, the synthetic retinamides, as a class, showed selective growth inhibition of both premalignant and malignant cells compared to normal human oral epithelial cells in culture. Within the retinamide class, 2CPR exhibited the greatest selectivity in the growth inhibition of premalignant and malignant cells. Among the non-retinoids analyzed, DFMO was a moderate to potent inhibitor of malignant and premalignant oral cell growth, respectively, and stimulated normal oral cell growth at low concentrations. Using this in vitro approach, we have identified several potential chemopreventive agents for oral cancer as selective growth inhibitors of premalignant ahd malignant human oral mucosa cells.

Impaired K(+) homeostasis and altered electrophysiological properties of post-traumatic hippocampal glia.

Traumatic brain injury (TBI) can be associated with memory impairment, cognitive deficits, or seizures, all of which can reflect altered hippocampal function. Whereas previous studies have focused on the involvement of neuronal loss in post-traumatic hippocampus, there has been relatively little understanding of changes in ionic homeostasis, failure of which can result in neuronal hyperexcitability and abnormal synchronization. Because glia play a crucial role in the homeostasis of the brain microenvironment, we investigated the effects of TBI on rat hippocampal glia. Using a fluid percussion injury (FPI) model and patch-clamp recordings from hippocampal slices, we have found impaired glial physiology 2 d after FPI. Electrophysiologically, we observed reduction in transient outward and inward K(+) currents. To assess the functional consequences of these glial changes, field potentials and extracellular K(+) activity were recorded in area CA3 during antidromic stimulation. An abnormal extracellular K(+) accumulation was observed in the post-traumatic hippocampal slices, accompanied by the appearance of CA3 afterdischarges. After pharmacological blockade of excitatory synapses and of K(+) inward currents, uninjured slices showed the same altered K(+) accumulation in the absence of abnormal neuronal activity. We suggest that TBI causes loss of K(+) conductance in hippocampal glia that results in the failure of glial K(+) homeostasis, which in turn promotes abnormal neuronal function. These findings provide a new potential mechanistic link between traumatic brain injury and subsequent development of disorders such as memory loss, cognitive decline, seizures, and epilepsy.

Frequency-dependent changes in cerebral blood flow and evoked potentials during somatosensory stimulation in the rat.

Contrary to the concept of neuronal-vascular coupling, cortical evoked potentials do not always correlate with blood flow responses during somatosensory stimulation at changing stimulus rates. The goal of this study is to clarify the effects of stimulus frequency on the relationship between somatosensory evoked potentials (SEPs) and cerebral blood flow. In rats anesthetized with alpha-chloralose, we measured SEPs by signal-averaging field potentials recorded with an electrode placed on dura overlying the hindlimb somatosensory cortex. Regional blood flow was simultaneously assessed in the same region with a laser-Doppler flow (LDF) probe. The contralateral sciatic nerve was stimulated with 0.1 A pulses at the frequencies of 1, 2, 5, 10 and 20 Hz. SEPs (both P1 and N1 components) declined with increasing frequency regardless whether stimulus duration (20 s) or number (100) were kept constant, suggesting that frequency is an important determinant of neuronal activity. In contrast, LDF responses increased to a maximum at 5 Hz, and do not correlate with SEPs. Because CBF should reflect integrated neuronal activity, we computed the sum of SEPS (summation operatorSEP = SEP x stimulus frequency) as an index of total neuronal activity at each frequency. Summation operatorSEP indeed correlates positively (P<0.001) with LDF responses. Thus, during somatosensory stimulation at various frequencies, cerebral blood flow is coupled to integrated neuronal activity but not to averaged evoked potentials.