Total and methyl-mercury content in bivalves,Mytilus galloprovincialis lamarck andOstrea edulis linnaeus: Relationship of biochemical composition and body size

Bulletin of Environmental Contamination and Toxicology -     

Progressive tubulointerstitial nephritis and chronic cholestatic liver disease

We report the clinical and morphological features of a distinctive hepatorenal disorder in four patients and review the five similar patients in the literature. The main clinical characteristics were early onset of cholestatic liver disease and progressive tubulointerstitial nephritis leading to renal death in early childhood. Liver histology showed disturbed architecture with nodular and acinar formations and portal fibrosis and bile duct proliferation. Histological abnormalities in the kidney were severe interstitial fibrosis and tubular atrophy and dilatation, while the typical features of nephronophthisis were lacking. These clinical and morphological characteristics distinguish our patients from the majority described, as having nephronophthisis and congenital hepatic fibrosis or any other known syndrome with concomitant hepatorenel involvement. We suggest that the association of cholestatic liver disease and progressive tubulointerstitial nephritis represents a new syndrome.     

Reactivating and protective effects of pyridinium compounds in human erythrocyte acetylcholinesterase inhibition by organophosphates in vitro

The reactivation of human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7) inhibited by O-ethyl-S-2-di-isopropylaminoethyl methylphosphonothioate (VX) and the protection against AChE inhibition by O-1,2,2-trimethylpropyl methylphosphonofluoridate (Soman) was studied with sixteen quaternized pyridinium compounds. TMB-4 which is known as a good reactivator of AChE inhibited by organophosphates proved to be the most effective reactivator. Of the tested newly synthetised compounds 3 were fairly good reactivators of methylethoxyphosphonylated AChE. These compounds have 2 pyridinium rings connected by a dimethylether link and a hydroxiiminomethyl group in position 2 of one pyridinium ring, while the radicals of the other pyridinium ring are benzoylcarbonyl, cyclohexylcarbonyl or amidocarbonyl residue.The rate of reactivation with these compounds followed a two-phase pattern, being fast at the beginning and then slowing down to an equilibrium. Kinetic treatment of the first-phase reaction course yielded the second-order rate constants of reactivation. All 3 compounds had similar reactivating efficiency (k _r values range from 0.8×10³ to 3.6×10³ M^–1 min^–1) and in effective concentrations (1 to 100 M) they also inhibited AChE (K _i(app) values range from 0.11 to 0.19 mM). Their reactivating properties were not better than those revealed by TMB-4 (k _r= 19.4×10³ M^–1 min^–1) which was tested as a reference compound.HGG-12, HGG-42 and HI-6 were also found to exert a good protective effect against AChE inhibition by Soman; no protection was obtained with TMB-4.     

Clinical characteristics of haemorrhagic fever with renal syndrome in children

From January 1988 to September 1989, seven patients (4 girls and 3 boys, aged 3–12 years) with haemorrhagic fever with renal syndrome (HFRS) were hospitalised at the University Children's Hospital in Belgrade. In four patients the disease appeared as a family outbreak, the others were sporadic cases. In six patients the clinical presentation was suggestive of HFRS, as they had fever with headache, myalgia, sore throat and gastrointestinal illness followed by renal abnormalities. However, severe haemorrhagic syndrome with petechia, haematoma, haematemesis and melaena was present in one patient only. Renal disease presented as nephritic syndrome and/or acute renal failure. Five patients recovered after 2–3 weeks without sequellae, one patient had decreased renal function 17 months after the start of the disease and the remaining patient died. In six patients the diagnosis of HFRS was confirmed serologically by a significant rise in antibody titres against hantaviruses, while in the patient with the fatal and fulminant course of the disease, the diagnosis was established on the basis of epidemiological and autopsy findings. We suggest that children living in endemic areas who develop an ill-defined, febrile and gastrointestinal disease with renal dysfunction should be evaluated for HFRS.     

Imiquimod treatment induces expression of opioid growth factor receptor: a novel tumor antigen induced by interferon-alpha?

PURPOSE: Imiquimod represents a synthetic local immune response modifier that has demonstrated efficacy in clearing basal cell carcinoma. Via interaction with Toll-like receptor 7 on immune cells, imiquimod induces local production of cytokines, such as interferon (IFN)-alpha. EXPERIMENTAL DESIGN: To more closely define and elucidate mechanisms leading to basal cell carcinoma clearance in vivo, we examined gene expression profiles of skin basal cell carcinoma before and after treatment with 5% imiquimod cream (Aldara) by using high-density oligonucleotide arrays. RESULTS: We show that imiquimod predominantly induces genes involved in different aspects of immune response. In addition to effects on immunity, imiquimod treatment modulates the expression of genes involved in the control of apoptosis and oncogenesis. Array data indicated that imiquimod treatment induces expression of opioid growth factor receptor, a molecule recently reported to be a target for antitumor antibody responses. Immunohistochemistry revealed in vivo up-regulation of opioid growth factor receptor protein on tumor and on infiltrating cells after treatment. By using basal cell carcinoma cell lines treated with IFN-alpha or imiquimod, we show that opioid growth factor receptor up-regulation is IFN-alpha-mediated, rather then directly imiquimod-mediated. By using tissue microarray containing 52 basal cell carcinomas, we demonstrate opioid growth factor receptor expression in almost half of the cases. Expression of opioid growth factor receptor correlated with a longer recurrence-free period in basal cell carcinoma that recurred after radiotherapy (Kaplan-Meier analysis, P = 0.041). CONCLUSIONS: In addition to its immunomodulatory and antiproliferative activity, opioid growth factor receptor seems to have a prognostic significance in basal cell carcinoma patients. Our data add to the growing list of basal cell carcinoma-associated tumor antigens.     

Adipose concentrations of organochlorine compounds and breast cancer recurrence in Long Island, New York.

Several studies have measured the association between blood or adipose concentrations of organochlorinated compounds (OCs), such as pesticides and polychlorinated biphenyls (PCBs), and breast cancer. The estrogenic effects of OCs might adversely affect breast cancer recurrence. The participants were 224 women with nonmetastatic breast cancer enrolled in a New York-based case-control study. Supercritical fluid extraction followed by gas chromatography was conducted on adipose surgical specimens to determine OC concentrations. The mean follow-up time from surgery was 3.6 years. Thirty women (13.4%) were diagnosed with a recurrence. The concentration of pesticides and PCBs was correlated with baseline age and body mass index, but not with cancer stage. The highest tertile of total PCB concentration was associated with an increased risk of recurrence [relative risk (RR), 2.9; 95% confidence interval (CI), 1.02-8.2 versus the lowest tertile]. The risk for the highest tertile of the PCB congener Ballschmiter and Zell 118 was 4.0 (95% CI, 1.3-4.9). There was an increased risk for the middle level of the most abundant pesticide, 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene (RR, 2.3; 95% CI, 0.9-5.7), and for beta-hexachlorocyclohexane, but not for their highest levels. Self-reported home termiticide exposure, alcohol consumption (> or = 1 drink/day), and race were not associated with prognosis. The RR for current cigarette smoking at diagnosis was 2.1 (95% CI, 0.9-5.1). In contrast to previous data showing no relationship between OC exposure and risk of breast cancer in these women, adipose PCB concentrations were associated with tumor recurrence. Pesticide levels were not related to recurrence.     

Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin

The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3β shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-dependent autophagic response might sensitize glioma cells to statin-induced apoptotic death.     

Evaluation of Dietary Intake and Anthropometric Status in 1–9-Year-Old Children Living in Serbia: National Food Consumption Survey according to the EU Menu Methodology

The Serbian Food Consumption Survey among 1–9-year-old-children was conceptualized and conducted in compliance with the principles, established protocols, and guidelines of the EU Menu project between 2017 and 2021. Valid data were collected for 576 individuals (290 1–3-year-old toddlers and 276 3–9-year-old children). Regardless of age and gender category, the majority (68.80%) of children had normal weights according to the Body Mass Index-for-age classification system. The median daily energy intake was 1406.71 kcal with no differences between the settlement types. The overall median contributions of carbohydrates, protein, and fat to the total energy intake were 47.54%, 14.06%, and 37.88%, respectively. The proportions of the macronutrient intake deviated from the dietary reference values with compliance to the recommendations being particularly poor for fat and fiber. The consumption of energy-dense food groups such as meat and meat products, fat and oil, sugar, and confections was more pronounced among older children. The survey results provide a valuable insight into the nutritional status and dietary habits of toddlers and children 1–9 years old living in Serbia. They may serve as an evidence platform for public health programs, a valuable asset for decision-makers, and a reliable reference to guide nutritional policies, diet monitoring, and interventions targeting this population group in the future.     

Cytokine expression in response to bacterial antigens in preterm and term infant cord blood monocytes

BACKGROUND: Neonatal susceptibility to bacterial infection is associated with an immature immune system, but the role of different bacterial antigens in specific responses is largely unknown. OBJECTIVE: To evaluate differences in intracellular cytokine response to physiologically relevant bacterial antigens in term and preterm infants as compared with adults. METHODS: Cord blood samples from preterm and term neonates and adult peripheral blood samples were cultured ex vivo with and without whole heat-killed bacteria. Intracellular leukocyte production of interleukin (IL)-6, IL-10, IL-12, and IL-8 responses was assessed by flow cytometry. RESULTS: Monocytes were the primary producers of all mediators. Escherichia coli was the most potent stimulant. Lactobacillus plantarum 299v activated fewer monocytes as compared with E. coli for all responses (p < 0.05), except for IL-12 in term neonates. IL-6 response to Staphylococcus epidermidis was lower in both groups of neonates as compared with adults (p = 0.023 and p = 0.001). IL-8 response to S. epidermidis was lower in term as compared with preterm neonates and adults (p = 0.003). IL-10 response to group B streptococci was lower in term neonates as compared with adults and higher in preterm as compared with term neonates (p = 0.015). CONCLUSIONS: Monocytes from term neonates compared to preterm neonates show a downregulated anti-inflammatory response to specific bacteria. High neonatal response to pathogenic E. coli in the preterm infant could cause uncontrolled inflammatory response, while lower IL-6 response to S. epidermidis in neonates may indicate a basis for vulnerability to S. epidermidis infection.