2‐(2‐Nitrovinyl)furan Promotes Oxidation of Cellular Proteins,Lipids, and DNA of Male Rat Liver and Kidney

The effect of 2‐(2‐nitrovinyl)furan on the redox status of male rat liver and kidney was evaluated. Twenty male rats were randomized into four groups; group A received olive oil and groups B, C, and D rats received 12.5, 25, and 50 mg/kg bodyweight of 2‐(2‐nitrovinyl)furan intraperitoneally, daily at 24 h interval, respectively, for 14 days. 2‐(2‐Nitrovinyl)furan significantly reduced (P < 0.05) alkaline phosphatase, alanine, and aspartate aminotransferase activities in male rat liver and kidney with a corresponding increase in serum. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and levels of reduced glutathione/glutathione disulfide (GSSG) ratio in the liver and kidney of 2‐(2‐nitrovinyl)furan‐treated rats decreased significantly (P < 0.05). In contrast, GSSG, protein carbonyl, conjugated dienes, lipid hydroperoxides, malondialdehyde, and fragmented DNA (%) in 2‐(2‐nitrovinyl)furan‐treated rats increased significantly (P < 0.05). Overall, data from this study revealed that 2‐(2‐nitrovinyl)furan exhibited its toxic effect by suppressing or depleting the antioxidant systems.     

Isolation and pathogenicity of a Bacillus sp. associated with a septicaemic condition in some tropical freshwater fish species

Observations made over a three-year period at the Fish Diseases Laboratory of the African Regional Aquaculture Centre (ARAC), Nigeria, revealed the gradual emergence of a new, highly infectious septicaemic condition in some widely cultivated freshwater fish species. The broad host range included: Heterobanchus bidorsalis, Clarias gariepinus, “Heteroclarias” (a hybrid of these two species, male and female respectively), Chrysichthys nigrodigitatus, and Cyprinus carpio. Clinical signs and pathological lesions associated with the condition were tyical, irrespective of the fish species affected; natural outbreaks apeared to be associated with stress due to environmental factors. The bacterium isolated from moribund and freshly-dead fishes was identified as a Bacillus sp., based on the observed cultural, morphological and biochemical characteristics. Fish reinfection trials confirmed that the isolate was the causative agent of the condition. Antibiotic sensitivity tests showed that the organism was sensitive to tetracycline hydrochloride.     

Chemically Modified N-Acylated Hyaluronan Fragments Modulate Proinflammatory Cytokine Production by Stimulated Human Macrophages

Low molecular mass hyaluronans are known to induce inflammation. To determine the role of the acetyl groups of low molecular mass hyaluronan in stimulating the production of proinflammatory cytokines, partial N-deacetylation was carried out by hydrazinolysis. This resulted in 19.7 ± 3.5% free NH₂ functional groups, which were then acylated by reacting with an acyl anhydride, including acetic anhydride. Hydrazinolysis resulted in bond cleavage of the hyaluronan chain causing a reduction of the molecular mass to 30–214 kDa. The total NH₂ and N-acetyl moieties in the reacetylated hyaluronan were 0% and 98.7 ± 1.5% respectively, whereas for butyrylated hyaluronan, the total NH₂, N-acetyl, and N-butyryl moieties were 0, 82.2 ± 4.6, and 22.7 ± 3.8%, respectively, based on ¹H NMR. We studied the effect of these polymers on cytokine production by cultured human macrophages (THP-1 cells). The reacetylated hyaluronan stimulated proinflammatory cytokine production to levels similar to LPS, whereas partially deacetylated hyaluronan had no stimulatory effect, indicating the critical role of the N-acetyl groups in the stimulation of proinflammatory cytokine production. Butyrylated hyaluronan significantly reduced the stimulatory effect on cytokine production by the reacetylated hyaluronan or LPS but had no stimulatory effect of its own. The other partially N-acylated hyaluronan derivatives tested showed smaller stimulatory effects than reacetylated hyaluronan. Antibody and antagonist experiments suggest that the acetylated and partially butyrylated lower molecular mass hyaluronans exert their effects through the TLR-4 receptor system. Selectively N-butyrylated lower molecular mass hyaluronan shows promise as an example of a novel semisynthetic anti-inflammatory molecule.     

Contributions of Subsurface Cortical Modulations to Discrimination of Executed and Imagined Grasp Forces through Stereoelectroencephalography

Stereoelectroencephalographic (SEEG) depth electrodes have the potential to record neural activity from deep brain structures not easily reached with other intracranial recording technologies. SEEG electrodes were placed through deep cortical structures including central sulcus and insular cortex. In order to observe changes in frequency band modulation, participants performed force matching trials at three distinct force levels using two different grasp configurations: a power grasp and a lateral pinch. Signals from these deeper structures were found to contain information useful for distinguishing force from rest trials as well as different force levels in some participants. High frequency components along with alpha and beta bands recorded from electrodes located near the primary motor cortex wall of central sulcus and electrodes passing through sensory cortex were found to be the most useful for classification of force versus rest although one participant did have significant modulation in the insular cortex. This study electrophysiologically corroborates with previous imaging studies that show force-related modulation occurs inside of central sulcus and insular cortex. The results of this work suggest that depth electrodes could be useful tools for investigating the functions of deeper brain structures as well as showing that central sulcus and insular cortex may contain neural signals that could be used for control of a grasp force BMI.     

Surface eroding, liquid injectable polymers based on 5-ethylene ketal ε-caprolactone

Liquid, injectable hydrophobic polymers are potentially useful as depot systems for localized drug delivery. Low molecular weight polymers of 5-ethylene ketal ε-caprolactone and copolymers of this monomer with D,L-lactide were prepared and their properties assessed with respect to their suitability for this purpose. The polymers were amorphous and of low viscosity, and the viscosity was adjustable by choice of initiator and/or by copolymerizing with D,L-lactide. Lower viscosity polymers were attained by using 350 Da methoxy poly(ethylene glycol) as an initiator in comparison to octan-1-ol, while copolymerization with D,L-lactide increased viscosity. The initiator used had no significant effect on the rate of mass loss in vitro, and copolymers with D,L-lactide (DLLA) degraded faster than 5-ethylene ketal ε-caprolactone (EKC) homopolymers. For the EKC-based polymers, a nearly constant degradation rate was observed. This finding was attributed to the hydrolytic susceptibility of the EKC-EKC ester linkage, which was comparable to that of DLLA-DLLA, coupled with a higher molecular weight of the water-soluble degradation product and the low initial molecular weight of the EKC-based polymers. Cytotoxicity of the hydrolyzed EKC monomer to 3T3 fibroblast cells was comparable to that of ε-caprolactone, suggesting that polymers prepared from EKC may be well tolerated upon in vivo implantation.     

Lophirones B and C Attenuate Acetaminophen‐Induced Liver Damage in Mice: Studies on Hepatic,Oxidative Stress and Inflammatory Biomarkers

Lophirones B and C are chalcone dimers with proven chemopreventive activity. This study evaluates the hepatoprotective effect lophirones B and C in acetaminophen‐induced hepatic damage in mice using biomarkers of hepatocellular indices, oxidative stress, proinflammatory factors and lipid peroxidation. Oral administrations of lophirones B and C significantly (p < 0.05) attenuated acetaminophen‐mediated alterations in serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, albumin and total bilirubin. Similarly, acetaminophen‐mediated decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6‐ phosphate dehydrogenase were significantly attenuated in the liver of mice. Increased levels of conjugated dienes, lipid hydroperoxides, malondialdehyde, protein carbonyl and fragmented DNA were significantly lowered by lophirones B and C. Levels of tumour necrosis factor‐α, interleukin‐6 and 8 were significantly lowered in serum of acetaminophen treated mice by the chalcone dimers. Overall, results of this study show that lophirones B and C halted acetaminophen‐mediated hepatotoxicity.     

Functional Characterization of the Chicken Peptide Transporter 1 (Pept1, Slc15a1) Gene

Dietary amino acids can be transported into intestinal epithelial cells as di- and tripeptides by the action of the peptide transporter, PepT1 (SLC15A1). Expression of the chicken PepT1 (cPepT1) gene changes in response to dietary crude protein level; however, the molecular mechanism governing this regulation is unknown. This study analyzed the promoter region of the cPepT1 gene. Using deletion analysis, positive-acting (? 314 to ? 261, ? 169 to ? 155, and ? 120 to ? 60) and negative-acting (? 419 to ? 386 and ? 214 to ? 169) regions were mapped in transfected chick embryo fibroblasts (CEF). The addition of neither amino acids Phe, Arg, or Val, nor the dipeptides Gly-Sar (glycyl-sarcosine), Gly-Pro, Gly-Phe, Met-Pro, Met-Lys or Lys-Lys, had an effect on cPepT1 promoter activity in transfected CEF. The cPepT1 promoter was more active in CEF and primary chicken intestinal cells than in chicken liver cells. This study represents a functional characterization of the molecular regulation of the chicken PepT1 gene.     

Redox status of the liver and kidney of 2,2-dichlorovinyl dimethyl phosphate (DDVP) treated rats

The effect of 2,2-dichlorovinyl dimethyl phosphate on redox homeostasis in male rats was investigated. Rats were grouped into four: A, B, C and D where A (the control) received orally 1 ml of distilled water; B, C and D (test groups) received orally 2.5, 5 and 10 mg/kg body weight of DDVP respectively for 28 days. DDVP administration significantly reduced (P < 0.05) the alkaline phosphatase activity in the liver and kidney with corresponding increases in the serum. Acid phosphatase activity increased significantly (P < 0.05) in liver and kidney, while there was no significant change (P > 0.05) in the serum acid phosphatase activity. There was also a significant decrease (P < 0.05) in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in the liver and kidney. Liver and kidney levels of GSH, vitamins C and E were also significantly reduced (P < 0.05). Serum malonidialdehyde and lipid hydroperoxide also increased significantly (P < 0.05) in all DDVP treated groups. The available data from this study revealed that DDVP brings about its toxicity through depletion of the antioxidant systems and thus exposing the cells and cellular macromolecules to oxidative attacks by reactive oxygen species generated either from its metabolites or other in vivo means.     

Enhancement of the antimalarial efficacy of amodiaquine by chlorpheniramine in vivo

Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical application of the reversal phenomenon.