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Biography 2012; 33(7): 661-664 PubMed PMID: 23391875 Citation  Keywords:  Chromosome Disorders:diagnosis, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 18, Down Syndrome:diagnosis, History, 19th Century, History, 20th Century, History, 21st Century, Humans, Pediatrics:history, Trisomy:diagnosis, United Kingdom, United S.   

: The aim of this study is to present a short biography of some important physicians and describe the most prominent differences between trisomy 13, 18 and 21. The authors present the most prominent differences between trisomy 13, 18 and 21. The work of many important physicians, geneticists, has helped in the process of recognition of congenital anomalies. This group of famous persons includes Patau, Edwards and Down....

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Clinical Trial 2012; 33(7): 680-683 PubMed PMID: 23391874 Citation  Keywords:  Aged, Arginine Vasopressin:blood, Carbidopa:adverse effects, Catechols:adverse effects, Dopamine Agonists:administration & dosage, Dose-Response Relationship, Drug, Drug Combinations, Drug Therapy, Combination, Female, Humans, Inappropriate ADH Syndrome:c.   

OBJECTIVES: Several cases of syndrome of inappropriate antidiuresis induced by anti-Parkinson agents have been reported. Our previous study demonstrated that pergolide and pramipexole stimulated elevation of plasma arginine vasopressin (AVP) levels in some patients with Parkinson's disease (PD), but that levodopa/carbidopa (300/30 mg/day) did not affect plasma AVP levels in treatment-naïve PD patients. On the basis of the binding profile of ropinirole to monoamine receptors, we hypothesized that ropinirole does not stimulate AVP secretion. The aim of this study was to test this hypothesis.

METHODS: Inclusion criteria were patients with probable PD suffering from a wearing-off phenomenon and who had been treated using levodopa/carbidopa with or without entacapone, but not with other classes of anti-Parkinson agents. Patients were excluded if they had at least one condition that could be associated with high AVP levels. Ropinirole was initiated at 0.5 mg 3 times daily, and daily dosages were increased by 1.5 mg/day on a biweekly basis up to 6 mg/day. Plasma AVP levels were determined every two weeks. Effects of escalating ropinirole dosage on plasma AVP levels were evaluated using a one-way analysis of variance for repeated measures, an a priori Dunnett multiple comparison test, and a regression analysis.

RESULTS: Of 16 patients enrolled, 11 patients (four males and seven females) completed the study. There was no statistically significant dose-response relationship between the ropinirole dosage and plasma AVP levels.

CONCLUSION: A minimal therapeutic dosage of ropinirole did not affect plasma AVP levels in patients with PD taking levodopa....

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Journal Article 2012; 33(7): 667-673 PubMed PMID: 23391873 Citation  Keywords:  Brain Chemistry, Criminology:economics, Humans, Mental Disorders:economics, Models, Economic, Punishment, Risk-Taking,.   

: Criminal behaviors have been associated with risk, time and social preferences in economics (Becker 1968; Davis 1988), criminology (Chamlin & Cochran 1997), and neurolaw (Goodenough & Tucker 2010). This study proposes a molecular neuroeconomic framework for the investigation into crime and punishment. Neuroeconomic parameters (e.g., risk-attitude, probability weighting, time discounting in intertemporal choice, loss aversion, and social discounting) are predicted to be related to criminal behavior. Neurobiological and neuroendocrinological substrates such as serotonin, dopamine, norepinephrine, cortisol (a stress hormone), sex hormones (e.g., testosterone), and oxytocin in brain regions such as the orbitofrontal cortex, the amygdala, and the cingulate may be related to the neuroeconomic parameters governing criminal behaviors. The present framework may help us develop "neurolaw" based on molecular neuroeconomics of criminal and antisocial decision-making processes....

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Journal Article 2012; 33(Suppl 3): 190-197 PubMed PMID: 23353866 Citation  Keywords:  Animals, Antioxidants:metabolism, Drug Interactions, Endoplasmic Reticulum:drug effects, Enzyme Activation:drug effects, Female, Muscle, Skeletal:drug effects, Peroxynitrous Acid:biosynthesis, Quercetin:analogs & derivatives, Rabbits, Sarcoplasmic Reticul.   

OBJECTIVES: We examined effect of novel quercetin derivatives on sarcoplasmic reticulum (SR) Ca-ATPase activity isolated from skeletal muscles and their potential to prevent injury of SERCA induced by peroxynitrite that is elevated in multiple pathological processes.

METHODS: SR was isolated by ultracentrifugation, ATPase activity of SERCA was measured by NADH-coupled enzyme assay. Sulfhydryl and carbonyl groups content was determined to test oxidation of SERCA. Conformational changes in ATP and calcium binding site were assessed using specific fluorescent labels.

RESULTS: Di(diacetylcafeoyl)-mono-(monoacetylcafeoyl) quercetin (DACQ) restored and diquercetin significantly decreased activity of SERCA in the presence of peroxynitrite. Diquercetin significantly decreased SERCA activity in absence of peroxynitrite. All tested quercetin derivatives decreased thiol group content of SR and caused change in SERCA conformation. Significant decrease of protein carbonyls was observed in SERCA treated with di(diacetylcafeoyl)-mono-(monoacetylcafeoyl) quercetin in the presence of peroxynitrite.

CONCLUSION: DACQ protected SERCA in SR against formation of carbonyls in vitro and protected activity of the pump against inhibition caused by peroxynitrite. However, none tested quercetin derivative did protect SERCA against conformational changes and sulfhydryl group oxidation. Diquercetin inhibited SERCA at relatively low concentrations in the presence of peroxynitrite. Diquercetin and DACQ may prove to be beneficial in treatment of cancer and inflammatory diseases, respectively....

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Journal Article 2012; 33(Suppl 3): 183-189 PubMed PMID: 23353865 Citation  Keywords:  Animals, Antioxidants:metabolism, Basal Metabolism:drug effects, Biomarkers:metabolism, Caspases:metabolism, Female, Homeostasis:drug effects, Melatonin:metabolism, Mice, Mice, Inbred BALB C, Models, Animal, Oxidative Stress:drug effects, Thiobarbituric A.   

OBJECTIVES: Melatonin is a hormone with strong antioxidant activity. It is biosynthesized in the pineal gland and serves in the biological signaling and control of the circadian rhythm. Though there is evidence of beneficial effects of melatonin, the substance was not investigated in greater details associated with specific regulation of oxidative stress in organs and tissues.

DESIGN: The experiment is based on exposure of BALB/c mice to doses from 10 µg to 1mg of melatonin. Mice were euthanized after one and 24 hours, respectively. Biochemical markers in plasma, ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS) and activity of caspase-3 were examined in selected organs.

RESULTS: We confirmed significant alteration in high-density lipoprotein and total cholesterols and glucose. After one day, levels of glucose and high-density lipoprotein cholesterol were decreased, while total cholesterol increased in a dose dependent manner. FRAP values increased in spleen, liver, kidney, heart, and brain indicating a growing potential of low molecular weight antioxidants 24 hours after exposure. However, TBARS values indicating oxidative stress were elevated in heart, kidney, and liver.

CONCLUSIONS: Despite the antioxidant properties of melatonin, its effect on the organism is more complicated. It influences not only the oxidative homeostasis but also the basal metabolism, as represented by, e.g., cholesterol and glucose. This substance could thus be used for therapeutical purposes such as amelioration of pathologies associated with generation of reactive species or some metabolic dysfunctions....

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Journal Article 2012; 33(Suppl 3): 166-172 PubMed PMID: 23353862 Citation  Keywords:  Animals, Bacterial Proteins:chemistry, Cells, Cultured, Chemical Fractionation, Cytokines:biosynthesis, Dinoprostone:biosynthesis, Female, Lactobacillus casei:metabolism, Lipopolysaccharides:chemistry, Molecular Weight, Nitric Oxide:biosynthesis, Peptidog.   

OBJECTIVES: Major medical indications of probiotic bacteria are conditions associated with the gastrointestinal tract. They exhibit not only the local but also systemic effects, the molecular mechanisms of which are poorly understood. We hypothesized that the action at remote sites of the body could be at least partially attributed to substances of the low molecular mass released from digested bacteria and able to cross the intestinal barrier. The aim of the study was the analysis of immunobiological properties of bacterial lysates and characterization of chemical constituents participating on this mode of action.

METHODS: Lactobacillus casei probiotic strain DN-114001 was employed. Lysates were prepared by passing bacteria through a French press (1500 psi) followed by lyophilisation. The fractions were prepared by the microfiltration of the crude lysate using the 3-, 10-, 30-, 50-, and 100-kDa cutoff filters (Amicon® Ultra 0.5 ml, Millipore Corp.). This procedure completely removes biologically active bacterial macromolecules such as peptidoglycan (PGN), lipoteichoic acid (LTA) and lipopolysaccharide (LPS). Effects of microfiltrates on the in vitro production of nitric oxide (NO), cytokines, and prostaglandin E2 (PGE2) were investigated in rat peritoneal cells.

RESULTS: The original crude lysate (≤10 µg/ml) activated the biosynthesis of NO, PGE2, and secretion of cytokines. The amount of the lysate needed for the preparation of microfiltered fractions exhibiting immunostimulatory effects was 10-fold higher (100 µg/ml). The molecules with the molecular mass ≤3 kDa were responsible for approximately 45% and 83% of the NO- and PGE2-enhancing activities of the crude lysate, respectively. The microfiltered fractions of the lysate also enhanced secretion of interleukin-6 and tumor necrosis factor-α but not that of interleukin-10 and interferon-γ.

CONCLUSION: The Lactobacillus casei probiotic strain DN-114001 contains low molecular mass (≤3 kDa) molecules possessing immunostimulatory properties. Their chemical nature remains to be identified....

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Journal Article 2012; 33(Suppl 3): 161-165 PubMed PMID: 23353861 Citation  Keywords:  Animals, Bacterial Toxins:toxicity, Biomass, Body Weight, Carcinogens:toxicity, Chemical and Drug Induced Liver Injury:epidemiology, Coturnix, Cyanobacteria:chemistry, Dose-Response Relationship, Drug, Hepatocytes:drug effects, Lethal Dose 50, Male, Marin.   

OBJECTIVES: Previous studies using oral administration of environmentally relevant doses of cyanobacterial biomass containing microcystins (MCs) induced only sub-lethal effects in experimental birds. Therefore, the objective of this study was to obtain data on avian high-dose toxicity of MCs and compute LD50, if possible, following the natural oral route of administration.

DESIGN: Responses of birds to single high-dose exposure to MCs were evaluated in fourteen-day old Japanese quail males (Coturnix coturnix japonica) with average body weight of 50 g which were randomly divided into five groups. Birds from four experimental groups were administered 7.5 ml of cyanobacterial biomass suspension containing increasing MCs quantities of 2500, 5000, 10000, and 20000 µg/kg using oral gavage. Controls received an equal dose of drinking water instead of the test substance. Birds were observed for clinical signs of acute toxicity. Survivors were killed on day 5 to obtain body and liver weights. A five-grade semi-quantitative system for histopathological liver damage scoring was used to compare cyanobacterial-biomass-exposed birds against controls.

RESULTS: No mortality occurred during the period of five days post exposure in both control and MCs-exposed groups and this high-dose experiment failed to provide data to compute the LD50. Nevertheless, marked sub-lethal effects were recognised in the damage of liver that included dose-dependent changes in the body/liver ratios and morphological changes ranging from mild vacuolar dystrophy to focal liver necroses in the highest exposure group. Hepatic lesions were mainly observed in the pericentral area of the liver.

CONCLUSIONS: Though maximum cyanobacterial biomass dose rates that could be administered to birds of the size were used in the present experiment and more pronounced hepatic lesions than after exposure to environmentally relevant doses were observed, birds would probably have survived unless killed for histopathology on day 5 of exposure. These results provide support to previously reported data on sub-lethal effects following exposure to cyanobacterial biomass containing MCs in birds and mortality occurring only in birds under combined action with other stressors....

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Journal Article 2012; 33(Suppl 3): 155-160 PubMed PMID: 23353860 Citation  Keywords:  4-Hydroxycoumarins:toxicity, Animals, Anticoagulants:toxicity, Biomass, Brain:drug effects, Carcinogens:toxicity, Cholinesterase Inhibitors:toxicity, Coturnix, Cyanobacteria:chemistry, Female, Heart:drug effects, Kidney:drug effects, Liver:drug effects, L.   

OBJECTIVES: The objective of this study was to examine the hypothesis that a combination of cyanobacterial biomass containing microcystins, acetylcholinesterase inhibitor and anticoagulant can enhance avian toxic effects produced by single exposures only.

METHODS: A total of 48 two-month-old Japanese quails (Coturnix coturnix japonica) with average body weight of 160 g were randomly divided into 8 experimental groups of six birds and sex ratio of 1:1. Experimental groups of control Japanese quails (C) and birds exposed to single and combined sub-lethal doses of paraoxon (P), bromadiolone (B), and microcystins in cyanobacterial biomass (M) included: C, P, P+B, B, B+M, P+M, M, and P+B+M. During the 10-day exposure birds in the respective groups received biomass containing 61.62 µg microcystins daily (i.e. 26.54 µg MC-RR, 7.62 µg MC-YR and 27.39 µg MC-LR), two 250 μg/kg doses of paraoxon, and two 500 mg/kg doses of bromadiolone. Group responses were compared using standard plasma biochemistry and antioxidant/oxidative stress parameters in tissues.

RESULTS: While single and double combinations of toxicants induced responses in individual biochemical parameters measured and evaluated using univariate statistical analysis, those in the triple exposure were most extensive. The principal component analysis of antioxidant/oxidative stress parameters (glutathione reductase, lipid peroxidation, and ferric reducing antioxidant power) in tissues (liver, kidney, heart, brain, lungs, gonads, and pectoralis major muscle) clearly separated the triple group (P+B+M) from all single and double exposure groups and the control and indicated thus marked joint effects in the overall pattern of antioxidant/oxidative stress responses of this group. The separation was driven by the modification of the ferric reducing antioxidant power levels in heart and brain and the cardiac lipid peroxidation level, in particular.

CONCLUSIONS: This experiment contributes to the understanding of the pathogenic mechanisms of combined sub-lethal exposure to natural toxins and agrochemicals and may be used for risk assessment of environmental pollution in birds....

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