Influence of gender on cocaine hepatotoxicity in CF-1 mice

Gender is known to play a role in the bioavailability, metabolism, and lethality of many toxic substances. This study was conducted to investigate the influence of gender on cocaine hepatotoxicity (CH) and lipopolysaccharide (LPS) potentiation of CH. Male and female CF-1 mice were orally administered 20 mg/kg body weight cocaine hydrochloride once daily for 7 days. Four hours after the last cocaine administration, the mice were administered 12 x 10(6) EU LPS (or equal volume of sterile saline) intraperitoneally. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were evaluated as indices of liver injury. Blood and liver glutathione (GSH), glutathione reductase (GRx), and catalase (CAT) activities were also determined to investigate the extent of oxidative stress induced by the treatments. Serum ALT and AST concentrations were elevated in all males receiving cocaine alone or cocaine + LPS. Furthermore, blood GSH and CAT were decreased and GRx activity was elevated in these same animals. Histological analysis revealed a high degree of hepatic focal necrosis in the male cocaine group, and severe hemorrhagic necrosis in the male cocaine + LPS group. Unlike males, females showed no damage resulting from cocaine or cocaine + LPS exposure, whereas testosterone-supplemented ovariectomized females displayed histological and biochemical profiles statistically similar to males. The results demonstrate that the extent of CH or LPS-potentiated CH is influenced by gender and sex hormones, particularly testosterone.     

Inhibition by prostaglandin PGA1 on the multiplication of influenza virus is a dose-dependent effect

Cyclopentenone prostaglandins (PGs), are strong inhibitors of the multiplicative cycle of a wide variety of enveloped RNA and DNA viruses. Their antiviral activity is generally associated with alterations in the synthesis or maturation of specific virus proteins. In this report, we describe the effect of cyclopentenone PGA1 on the replication of influenza A virus Ulster 73 in LLC-MK2 cells. PGA1 was found to inhibit viral replication in a dose-dependent fashion and virus particle yield was reduced at a PGA1 concentration, which did not suppress protein synthesis in mock-infected cells. The kinetic of late viral protein synthesis was delayed in PGA1-treated cells till 10 h post-infection; after that period, viral polypeptide synthesis appeared to be similar in PGA1-treated as well as untreated cells both infected by Ulster 73 virus. This finding suggests that PGA1 might interfere with one or more events in the viral multiplicative cycle such as protein synthesis and assembly, correct insertion of virus polypeptides into the cell membrane and, or maturation of Ulster 73 virion particles. In particular, inhibition of viral replication in LLC-MK2 cells by PGA1 is accompanied by the induction of a cellular polypeptide of 70K molecular weight. We identified this cell protein as a heat shock protein (HSP) related to the inducible isoform of HSP 70, a polypeptide of 72K molecular weight. Induction of this polypeptide by PGA1 was found to be dose-dependent and a substantial accumulation could be seen at a PGA1 concentration that did not inhibit cell protein synthesis in uninfected cells. HSP 70 synthesis started after the beginning of PGA1 treatment and remained at the same level for at least 10 h, leading us to hypothesize that the delay of production of late Ulster 73 proteins could be the consequence of HSP 70 synthesis. These results suggest that HSP 70 could play a role in the antiviral activity of cyclopentenone PGA1 in LLC-MK2 cells.     

Environmental risk factors for type 1 diabetes in Rome and province.

BACKGROUND: In subjects genetically susceptible to type 1 diabetes, exposure to environmental factors during the gestational period, the neonatal period, and the first years of life is thought to play an important role in triggering the immune process leading to beta cell destruction. AIMS: To investigate risk factors for inhabitants of continental Italy. METHODS: A case-control study of 150 type 1 diabetes cases and 750 control subjects (age range 6-18 years) was carried out in Rome and its province, measuring the exposure to environmental risk factors. RESULTS: Three environmental factors were found to occur significantly more in the diabetic group than in the controls. During the mothers' pregnancies, the one risk factor which proved to be higher in diabetics than in controls was maternal infectious disease. During the neonatal period, no risk factors associated with the disease were detected. During early life, eczema and a short duration of breast feeding (less than three months), occurred significantly more in diabetic cases than controls. CONCLUSION: Eczema and breast feeding for less than three months are risk factors for type 1 diabetes in a southern European population. The type, duration, and mode of treatment for infectious diseases during pregnancy need additional investigation as risk factors for type 1 diabetes.     

Length of gestation and gender are associated with HLA genotypes at risk for Type 1 diabetes (Italian DIABFIN 3).

AIM: The aim of this study, which is part of the ongoing DIABFIN project, was to correlate HLA class II genotypes, classified for their effect on susceptibility to Type 1 diabetes (T1D), with various risk factors during pregnancy and the neonatal period. METHODS: Cord blood was collected from 4349 neonates; 1.0% were at high HLA risk (HR), 9.0% at moderate HLA risk (MR), and 90.0% at low HLA risk (LR) for T1D. Information about the mother's pregnancy, type of delivery, the neonates' clinical features at birth, and family history for autoimmune diseases were collected. RESULTS: Significant correlations were found between the different HLA risk categories and length of gestation, even when adjusted for sex, weight and length at birth of the neonate, birth order and mother's age (adjusted P = 0.007). The male : female ratio tended to increase from the LR to the HR category, from 1.00 and 1.21, respectively, in the LR and MR groups, to 1.62 in the HR group (P = 0.05). CONCLUSIONS: Length of gestation is inversely correlated with HLA risk categories for T1D. The higher the HLA risk for T1D, the shorter the gestational age, especially in male neonates.     

Diagnostic imaging in athletes with chronic lower leg pain

OBJECTIVE: Our purpose is to describe the imaging features in athletes with chronic lower leg pain, emphasizing the role of MRI and CT, which are the diagnostic tools with the highest sensitivity and specificity in the differential diagnosis of lower leg pain. Moreover, a diagnostic algorithm in patients with chronic lower leg pain is proposed. CONCLUSION: Plain radiography has a low sensitivity but may reveal tibial stress fractures, bone tumors, and soft-tissue calcification. CT and MRI may be useful to better evaluate the abnormalities shown by plain radiography.     

Non-invasive treatment of the sigmoid volvulus. A pediatric case report

Sigmoid volvulus occurs when the sigmoid colic loop gets wrapped around its own mesocolon. While this condition is categorized as an extremely rare emergency in the pediatric population, diagnosis is often difficult due to the fact that its aspecific manifestations or sneaky symptoms are similar to other medical conditions. The available treatment options remain controversial up to this day, and the non-operative approach is more preferred in treating hemodynamic stable patients.This paper examines the case study of a 13-year-old girl suffering from sigmoid volvulus, who was treated with water-soluble contrast enema, in order to determine whether this method is efficient and effective in successfully treating the pathology of this condition.