Local effects and global impact in neurotoxicity and neurodegeneration: The Xi"an International Neurotoxicology Conference

'Neurotoxicity and Neurodegeneration: Local Effect and Global Impact' was the theme of the Xi"an International Neurotoxicology Conference (XINC), held in Xi"an, June 2011. The Conference was a joint event of the 13th Biennial Meeting of the International Neurotoxicology Association (INA-13) and the 11th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health (NEUREOH-11) of the Scientific Committee on Neurotoxicology and...

Local effects and global impact in neurotoxicity and neurodegeneration: The Xi"an International Neurotoxicology Conference

'Neurotoxicity and Neurodegeneration: Local Effect and Global Impact' was the theme of the Xi"an International Neurotoxicology Conference (XINC), held in Xi"an, June 2011. The Conference was a joint event of the 13th Biennial Meeting of the International Neurotoxicology Association (INA-13) and the 11th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health (NEUREOH-11) of the Scientific Committee on Neurotoxicology and...

Reovirus infection activates JNK and the JNK-dependent transcription factor c-Jun.

Viral infection often perturbs host cell signaling pathways including those involving mitogen-activated protein kinases (MAPKs). We now show that reovirus infection results in the selective activation of c-Jun N-terminal kinase (JNK). Reovirus-induced JNK activation is associated with an increase in the phosphorylation of the JNK-dependent transcription factor c-Jun. Reovirus serotype 3 prototype strains Abney (T3A) and Dearing (T3D) induce significantly more JNK activation and c-Jun phosphorylation than does the serotype 1 prototypic strain Lang (T1L). T3D and T3A also induce more apoptosis in infected cells than T1L, and there was a significant correlation between the ability of these viruses to phosphorylate c-Jun and induce apoptosis. However, reovirus-induced apoptosis, but not reovirus-induced c-Jun phosphorylation, is inhibited by blocking TRAIL/receptor binding, suggesting that apoptosis and c-Jun phosphorylation involve parallel rather than identical pathways. Strain-specific differences in JNK activation are determined by the reovirus S1 and M2 gene segments, which encode viral outer capsid proteins (sigma1 and mu1c) involved in receptor binding and host cell membrane penetration. These same gene segments also determine differences in the capacity of reovirus strains to induce apoptosis, and again a significant correlation between the capacity of T1L x T3D reassortant reoviruses to both activate JNK and phosphorylate c-Jun and to induce apoptosis was shown. The extracellular signal-related kinase (ERK) is also activated in a strain-specific manner following reovirus infection. Unlike JNK activation, ERK activation could not be mapped to specific reovirus gene segments, suggesting that ERK activation and JNK activation are triggered by different events during virus-host cell interaction.

Isolation, structural assignment and total synthesis of Barmumycin

Barmumycin was isolated from an extract of the marine actinomycete Streptomyces sp. BOSC-022A and found to be cytotoxic against various human tumor cell lines. Based on preliminary one- and two-dimensional 1H- and 13C-NMR spectra, the natural compound was initially assigned the structure of macrolactone-type compound 1, which was later prepared by two different routes. However, major spectroscopic differences between isolated barmumycin and 1 led to revision of the proposed structure as E-16. Based on synthesis of this new compound, and subsequent spectroscopic comparison of it to an authentic sample of barmumycin, the structure of the natural compound was indeed confirmed as that of E-16.

A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline.

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Effect of feed fat by-products with trans fatty acids and heated oil on cholesterol and oxycholesterols in chicken

Chicken is the most widely consumed meat all over the world due to chickens being easy to rear, their fast growth rate and the meat having good nutritional characteristics. The main objective of this paper was to study the effects of dietary fatty by-products in low, medium and high levels of oxidized lipids and trans fatty acids (TFAs) on the contents of cholesterol and oxycholesterols in meat, liver, and plasma of chickens. A palm fatty acid distillate, before and after hydrogenation, and a sunflower-olive oil blend (70/30, v/v) before and after use in a commercial frying process were used in feeding trials after adding 6% of the fats to the feeds. Highly oxidized lipid and TFA feeds significantly increased the contents of cholesterol and oxycholesterols in all tissues of chicken (0.01 < p <= 0.05). The contents of oxycholesterols in chicken meat, liver and plasma obtained from TFA feeding trials varied between 17 and 48 μg/100 g in meat, 19-42 μg/100 g in liver and 105-126 μg/dL in plasma. In contrast, in the oxidized lipid feeding trials, oxycholesterols varied between 13 and 75 μg/100 g in meat, 30-58 μg/100 g in liver and 66-209 μg/dL in plasma. Meat from chickens fed with feeds containing high levels of TFAs or oxidized lipids may contribute to higher ingestion of cholesterol and oxycholesterols by humans.

Biogeochemical processes controlling oxygen and carbon isotopes of diatom silica in Late Glacial to Holocene lacustrine rhythmites

Biogeochemical cycles and sedimentary records in lakes are related to climate controls on hydrology and catchment processes. Changes in the isotopic imposition of the diatom frustules (δ 18 O diatom and δ 13 C diatom ) in lacustrine sediments can be used to reconstruct palaeoclimatic and palaeoenvironmental changes. The Lago Chungará (Andean Altiplano, 18°15 ′ S, 69°10 ′ W, 4520 masl) diatomaceous laminated sediments are made up of white and green multiannual rhythmites. White laminae were formed during short-term diatom super-blooms, and are composed almost exclusively of large-sized Cyclostephanos andinus.These diatoms bloom during mixing events when recycled nutrients from the bottom waters are brought to the surface and/or when nutrients are introduced from the catchment during periods of strong runoff. Conversely, the green laminae are thought to have been deposited over several years and are composed of a mixture of diatoms (mainly smaller valves of C. andinus and Discostella stelligera ) and organic matter. These green laminae reflect the lake's hydrological recovery from a status favouring the diatom super-blooms (white laminae) towards baseline conditions. δ 18 O diatom and δ 13 C diatom from 11,990 to 11,530 cal years BP allow us to reconstruct shifts in the precipitation/evaporation ratio and changes in the lake water dissolved carbon concentration, respectively. δ 18 O diatom values indicate that white laminae formation occurred mainly during low lake level stages, whereas green laminae formation generally occurred during high lake level stages. The isotope and chronostratigraphical data together suggest that white laminae deposition is caused by extraordinary environmental events. El Niño-Southern Oscillation and changes in solar activity are the most likely climate forcing mechanisms that could trigger such events, favouring hydrological changes at interannual-to-decadal scale. This study demonstrates the potential for laminated lake sediments to document extreme pluriannual events.

Local effects and global impact in neurotoxicity and neurodegeneration: The Xi"an International Neurotoxicology Conference

'Neurotoxicity and Neurodegeneration: Local Effect and Global Impact' was the theme of the Xi"an International Neurotoxicology Conference (XINC), held in Xi"an, June 2011. The Conference was a joint event of the 13th Biennial Meeting of the International Neurotoxicology Association (INA-13) and the 11th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health (NEUREOH-11) of the Scientific Committee on Neurotoxicology and...

Isolation, structural assignment and total synthesis of Barmumycin

Barmumycin was isolated from an extract of the marine actinomycete Streptomyces sp. BOSC-022A and found to be cytotoxic against various human tumor cell lines. Based on preliminary one- and two-dimensional 1H- and 13C-NMR spectra, the natural compound was initially assigned the structure of macrolactone-type compound 1, which was later prepared by two different routes. However, major spectroscopic differences between isolated barmumycin and 1 led to revision of the proposed structure as E-16. Based on synthesis of this new compound, and subsequent spectroscopic comparison of it to an authentic sample of barmumycin, the structure of the natural compound was indeed confirmed as that of E-16.

Belgian experience with triple therapy with boceprevir and telaprevir in genotype 1 infected patients who inject drugs.

No data have been reported yet on treatment outcome in persons who inject drugs (PWID) infected with hepatitis C virus treated with boceprevir or telaprevir in combination with peginterferon (Peg IFN) and ribavirin (RBV). Additionally, there are concerns about the safety of boceprevir and telaprevir in some subgroups of patients with hepatitis C (HCV). In a cohort of HCV patients infected with genotype 1 in Belgium, treatment outcome of patients infected due to IV drug use was analyzed and compared with patients who have no history of substance use. The study population consisted of 179 patients: 78 PWID and 101 controls treated with boceprevir (n = 79) or telaprevir (n = 100) additional to Peg IFN and RBV; 53 (30%) had advanced disease (F3, F4) and 79 (44%) had an antiviral therapy previously. There were no significant differences in the baseline characteristics between both groups, except that PWID patients were more frequently infected with genotype 1a (67% vs 21%), were younger and were predominantly male. Psychiatric complaints during follow-up occurred more frequently in the PWID patients: 24% versus 11% (P = .02). Treatment failure for other reasons than absence of viral response was 70% and 64% in PWID and non-PWID respectively. The sustained viral response (SVR) rates were similar in both groups (71% in PWID vs 72% in non-PWID); with a non-inferiority test with -5% margin there is a difference of -1% (95% CI [-15%, 13%]) and P = 0.30. There are no reasons to exclude PWID from treatment with boceprevir, telaprevir and novel antiviral therapies. J. Med. Virol. 88:94-99, 2016. © 2015 Wiley Periodicals, Inc.

Exercise performed immediately after fructose ingestion enhances fructose oxidation and suppresses fructose storage.

BACKGROUND: Exercise prevents the adverse effects of a high-fructose diet through mechanisms that remain unknown. OBJECTIVE: We assessed the hypothesis that exercise prevents fructose-induced increases in very-low-density lipoprotein (VLDL) triglycerides by decreasing the fructose conversion into glucose and VLDL-triglyceride and fructose carbon storage into hepatic glycogen and lipids. DESIGN: Eight healthy men were studied on 3 occasions after 4 d consuming a weight-maintenance, high-fructose diet. On the fifth day, the men ingested an oral (13)C-labeled fructose load (0.75 g/kg), and their total fructose oxidation ((13)CO2 production), fructose storage (fructose ingestion minus (13)C-fructose oxidation), fructose conversion into blood (13)C glucose (gluconeogenesis from fructose), blood VLDL-(13)C palmitate (a marker of hepatic de novo lipogenesis), and lactate concentrations were monitored over 7 postprandial h. On one occasion, participants remained lying down throughout the experiment [fructose treatment alone with no exercise condition (NoEx)], and on the other 2 occasions, they performed a 60-min exercise either 75 min before fructose ingestion [exercise, then fructose condition (ExFru)] or 90 min after fructose ingestion [fructose, then exercise condition (FruEx)]. RESULTS: Fructose oxidation was significantly (P < 0.001) higher in the FruEx (80% ± 3% of ingested fructose) than in the ExFru (46% ± 1%) and NoEx (49% ± 1%). Consequently, fructose storage was lower in the FruEx than in the other 2 conditions (P < 0.001). Fructose conversion into blood (13)C glucose, VLDL-(13)C palmitate, and postprandial plasma lactate concentrations was not significantly different between conditions. CONCLUSIONS: Compared with sedentary conditions, exercise performed immediately after fructose ingestion increases fructose oxidation and decreases fructose storage. In contrast, exercise performed before fructose ingestion does not significantly alter fructose oxidation and storage. In both conditions, exercise did not abolish fructose conversion into glucose or its incorporation into VLDL triglycerides. This trial was registered at clinicaltrials.gov as NCT01866215.

Atribuição inequívoca de deslocamentos químicos de RMN de ¹H e 13C de plumierídeo isolado da Allamanda cathartica

There are NMR data of ¹H and 13C of the iridoid plumieride, but controversy related to the assignments of the protons H-3 or H-10 and carbons C-6 or C-7 and C-3 or C-10 are described in the literature. There are a little discussion regarding to the resonance assignment of protons of the glycoside unity. Analysis based on 2D shift correlated NMR spectra (COSY, HETCOR, HETCORLR) and NOE difference ¹H NMR spectra allowed to assign unambigously the chemical shift of ¹H and 13C of plumieride which has been found in the literature with non coincident values.