Biomarkers of imidacloprid toxicity in Japanese quail, Coturnix coturnix japonica.

The in vivo effect of the oral sublethal doses of 3.014 mg kg-1 of IMI (1/25 LD50) for 1, 7, 14, and 28 days every other day on Japanese quail was investigated. The results revealed that certain biomarkers in the selected tissues of the quail such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), aminotransaminases (alanine aminotransferase, ALT, and aspartate aminotransaminase, AST), phosphatases (acid phosphatase, ACP, and alkaline phosphatase, ALP), lactate dehydrogenase (LDH), adenosine-triphosphatase (ATPase), glutathione-S-transferase (GST), lipid peroxidation (LPO), and blood glucose showed significant inductions, while significant reductions in the levels of glutathione-reduced (GSH), deoxyribonucleic acid (DNA), and ribonucleic acid (RNA) were noticed. In this study, the molecular mechanisms of the toxic effects of imidacloprid on quails were elucidated regarding neurotoxicity, hepatotoxicity, oxidative stress, lipid peroxidation, antioxidant activity, and genotoxicity. Because IMI induced alterations in the levels of these biomarkers in Japanese quail; therefore, Japanese quail as a wild avian can be used as a suite bioindicator to detect imidacloprid toxicity.

Pharmacokinetics of genistein distribution in blood and retinas of diabetic and non-diabetic rats.

Genistein, a natural tyrosine kinase inhibitor, may act as an intraocular antiangiogenic agent. Its therapeutical use, however, is limited by its nonlinear pharmacokinetics. We aimed to determine genistein's kinetics and retinal tissue distributions in normal and diabetic rats. We developed an isocratic, reverse-phase C18 HPLC system to measure genistein concentration in blood and retinas of streptozotocin (65 mg/kg IV)-diabetic and non-diabetic rats receiving two types of genistein-rich diet (150 and 300 mg/kg) for ten days. Genistein's decay exhibited a two-compartmental open model. Half-lives of distribution and elimination were 2.09 and 71.79 min, with no difference between groups. Genistein steady-state concentration in blood for 150 and 300 mg/kg diet did not differ between diabetic (0.259 ± 0.07 and 0.26 ± 0.06 µg/ml) and non-diabetic rats (0.192 ± 0.05 and 0.183 ± 0.09 µg/ml). In retina, genistein concentration was significantly higher in diabetic rats (1.05 ± 0.47 and 0.997 ± 0.47 µg/gm wt. vs. 0.087 ± 0.11 and 0.314 ± 0.18 µg/gm wt., p < 0.05). The study determined that increasing genistein dose did not change its bioavailability, perhaps due to the poor aqueous solubility. The retina's increased genistein could be due to increased permeability of blood-retinal barrier that occurs early in diabetes.

Leukemic Stem Cell (CD34+/CD38-/TIM3+) Frequency in Patients with Acute Myeloid Leukemia: Clinical Implications.

This study aimed to address the prognostic relevance of CD34+/CD38-/TIM3+ leukemic stem cell (LSC) frequency in patients with acute myeloid leukemia (AML) and its impact on patient outcome. We analyzed the expression of LSC markers (CD34+/CD38-/TIM3+) using flow cytometry in bone marrow samples of 53 AML cases before and after induction chemotherapy. The LSC frequency at diagnosis was significantly higher compared with that postinduction (P < .001). Patients were categorized into high LSC expressers (≥ median) and low expressers (< median). Patients with AML with high number of LSCs at diagnosis had significantly lower induction of remission response (P = .0104), shorter disease-free survival, and shorter overall survival (P < .001 for both) compared with those with lower LSC count. Cox regression analysis revealed that LSC frequency at diagnosis is an independent prognostic factor in AML. Assessment of LSCs (CD34+/CD38-/TIM3+) at diagnosis is recommended for refining of AML risk stratification.

Place of malaria in the etiologies of febrile attacks in children in a conflict area zone: Case of department of pediatric regional hospital of Timbuktu

Introduction: Malaria, a public health problem in tropical countries, depends on several factors, some of which are social and environmental. In Mali in the Sahel zone, a socio-security crisis has prevailed in recent years. It was therefore interesting to study the epidemiology of this condition in situation. Objective: To determine the frequency of malaria among febrile syndromes in children aged 1 to 59 months in the pediatric ward of the Regional Hospital of Timbuktu. Material and methods: the study was longitudinal retrospective descriptive for a period from January 1 to December 31, 2015. The data were collected with fact sheets and consultation records. They were captured and analyzed on the Statistical Package for Social Scientist (SPSS) software version 21. Results: a total of 789 children hospitalized, 276 children had a febrile syndrome (35%). During the study period, we collected 180 cases of malaria, with a positive biological examination. The hospital frequency of malaria was 22.8% (180/789) and a frequency in febrile syndromes of 65.2% (180/276) of malaria cases. Of these 180 cases, 147 cases of uncomplicated malaria (81.7%) and 33 cases of severe malaria (18.3%) were found. In 34.8%, the etiology of febrile syndromes was other than malaria. Seasonal variation in malaria was found in terms of months of the year, peaking in September. The hospital lethality was 1.1% in our series. Conclusion: Malaria was the leading febrile syndromes among children under 5 in hospitals in Tombouctou

Study of Sex Hormone-binding Globulin Gene Polymorphism and Risk of Type 2 Diabetes Mellitus in Egyptian Men.

OBJECTIVES: Conditions of hypoandrogenism in men have been linked to insulin resistance, suggesting that alterations in normal sex steroid physiology could play a role in the pathogenesis of Type 2 diabetes mellitus (T2DM). Sex hormone-binding globulin (SHBG) gene polymorphisms may be the cause of sex steroid alteration. The aim of this work is to study the effect of SHBG gene polymorphisms on the risk of T2DM through its impact on testosterone and oestradiol level in Egyptian men. SUBJECTS AND METHODS: A case control study was performed in the diabetes clinic at Zagazig University Hospital on 185 males with Type 2 diabetes and their matched healthy controls. Two polymorphisms (rs6257 and rs6259) of the gene encoding SHBG were genotyped and serum levels of SHBG, testosterone and oestradiol were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Carriers of rs6257 variant allele (CC or CT) and carriers of rs6259 wild allele (GG) appear to have a high risk of diabetes than carriers of other alleles (OR 2.241, 1.585 and 2.391, respectively). They also showed a significant decrease in plasma level of both SHBG and testosterone and a significant increase in oestradiol blood level compared with carriers of other alleles. CONCLUSIONS: Sex hormone-binding globulin gene polymorphisms at position rs6257 and rs6259 are associated with higher risk of T2DM in Egyptian men, through lowering circulating levels of SHBG and consequently, lowering testosterone and elevating oestradiol level.

Honey feeding protects kidney against cisplatin nephrotoxicity through suppression of inflammation.

Cisplatin is a highly effective chemotherapeutic drug used to treat a wide variety of solid tumors. However, its use was limited due its dose-limiting toxicity to the kidney. Currently, there are no therapies available to treat or prevent cisplatin nephrotoxicity. Honey is a naturally occurring complex liquid and widely used in traditional Ayurvedic medicine to treat many illnesses. However, its effect on cisplatin nephrotoxicity is unknown. To determine the role of honey in cisplatin nephrotoxicity, animals were pretreated orally for a week and then cisplatin was administered. Honey feeding was continued for another 3 days. Our results show that animals with cisplatin-induced kidney dysfunction, as determined by increased serum creatinine, which received honey feeding had less kidney dysfunction. Improved kidney function was associated with better preservation of kidney morphology in honey-treated group as compared to the cisplatin alone-treated group. Interestingly, honey feeding significantly reduced cisplatin-induced tubular epithelial cell death, immune infiltration into the kidney as well as cytokine and chemokine expression and excretion as compared to cisplatin treated animals. Western blot analysis shows that cisplatin-induced increase in phosphorylation of NFkB was completely suppressed with honey feeding. In conclusion, honey feeding protects the kidney against cisplatin nephrotoxicity through suppression of inflammation and NFkB activation.

Preparation of targeted isoniazid microspheres.

Isoniazid (INH) albumin microspheres were prepared by two different stabilization processes: chemical denaturation using glutaraldehyde and heat denaturation. The extent of stabilization was characterized by the solubility of the microspheres. In vitro drug release rates were correlated to the stability of the microspheres and the results showed that the more denatured the albumin by heat stabilization, the slower the drug release rate. A factorial concept has been utilized to synthesize microspheres suitable for passive targeting to the lungs by varying protein concentration, stabilization temperature, time and aqueous volume. These factors significantly affected the sphere size, payload and a release profile of the drug. As the severity of the denaturation conditions increased, the payload decreased and the rate of drug release was slowed. The microspheres carrying isoniazid were followed in experimental animals to validate the targeting process.

Aminoglycoside levels in the rabbit vitreous cavity after intravenous administration.

PURPOSE: To determine the penetration of gentamicin and amikacin into the rabbit vitreous cavity after their intravenous administration. METHODS: Gentamicin (1.6 mg/kg every 8 hours) and amikacin (6 mg/kg every 12 hours) were administered intravenously to 25 rabbits that had previously had the lens and vitreous removed from 43 eyes. For each drug, ocular inflammation was induced in one group of eyes by injection of heat-killed Staphylococcus epidermidis, while the other group was maintained as a control. Samples from the vitreous cavity were taken at regular intervals for 72 hours after beginning the intravenous medications and were analyzed for drug concentrations. RESULTS: The maximum intravitreal concentration +/- SD achieved for gentamicin was 1.8 +/- 0.5 microgram/ml. The maximum intravitreal concentration for amikacin was 8.5 +/- 3.2 micrograms/ml. Inflamed eyes demonstrated higher concentrations than did those without inflammation. CONCLUSIONS: In a rabbit model with conditions optimized to enhance penetration of antimicrobials into the vitreous cavity after intravenous administration, neither gentamicin nor amikacin penetrated sufficiently to reach potentially therapeutic concentrations consistently for either Pseudomonas or S epidermidis organisms.

Polyamines inhibit nitric oxide synthase in rat cerebellum.

The polyamines spermine, spermidine and putrescine share some basic structural features with L-arginine, the substrate of nitric oxide (NO) synthase. The effects of the polyamines on neuronal NO synthase activity were studied in cytosolic preparations of rat cerebellum and cultured cerebellar granule neurons. Spermine, spermidine and putrescine all inhibited the conversion of [3H]L-arginine to [3H]L-citrulline by NO synthase, with the following rank order of potency: spermine > spermidine > putrescine. These inhibitory effects of the polyamines on [3H]L-citrulline formation were also observed in intact cultured cerebellar granule neurons upon stimulation of N-methyl-D-aspartate (NMDA) receptors. Evidence was obtained, however, that endogenous polyamines are not involved in regulation of NMDA-stimulated NO synthase activity. Thus, the observed inhibitory effects of exogenous polyamines might not reflect a physiological role in modulating NO generation in neurons.

Effect of 4-(diethylamino)benzaldehyde on ethanol metabolism in mice.

The compound 4-(diethylamino)benzaldehyde (DEAB) is a potent inhibitor of cytosolic (class 1) aldehyde dehydrogenase (ALDH) in vitro and can overcome cyclophosphamide resistance in murine leukemia cells characterized by their high content of ALDH. In this study, we examined the in vivo effect of DEAB in mice on ethanol metabolism and on antipyrine clearance as a measure of the microsomal mixed function oxidase activity. DEAB administered in doses of 50 and 100 mg/kg increased the blood acetaldehyde concentration and decreased the plasma acetate concentration in mice treated with ethanol. A pharmacokinetic approach demonstrated that DEAB in doses of 50 and 100 mg/kg inhibited the fraction of ethanol converted to acetate by 32.5 and 67.5%, respectively. This inhibition was comparable with that produced by disulfiram. DEAB produced optimal inhibition of ALDH 10-15 min after administration. DEAB did not change the half-life or the total clearance of antipyrine. We conclude that DEAB is a potent inhibitor of ALDH in vivo and has no effect on the mixed function oxidase activity as determined by antipyrine clearance.

The electronic and thermodynamic aspects of Ah receptor binding. A new structure-activity model: I. The polychlorinated dibenzo-p-dioxins.

A new quantitative structure-activity model for the aromatic hydrocarbon (Ah) receptor, which completely eliminates multiple regression analysis in its formulation, is reported. Taking the polychlorinated dibenzo-p-dioxins (PCDDs) as model xenobiotics, the binding affinity of a PCDD relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was found to be analytically related to the electron affinities, entropies and lipophilicities of PCDD and TCDD. The reported mathematical model is capable of qualitatively explaining and quantitatively estimating the in vitro binding affinities of PCDDs and related xenobiotics to the Ah receptor. Accordingly, a halogenated aromatic compound is expected to have a high affinity for the cytosolic protein compared to TCDD if it is less lipophilic, has a higher electron affinity and lower entropy than TCDD. In addition, the LD50s of PCDDs in selected mammalian species are shown to have similar sigmoidal dependence on their lipophilicities, electron affinities and entropies, in agreement with the hypothesis that the toxicities of PCDDs and related xenobiotics are mediated through binding to the Ah receptor and that the trend in the LD50s and other toxic responses of PCDDs in animals are similar.

Immunogenicity evaluation of protein hydrolysates for hypoallergenic infant formulae.

Casein and soy protein were enzymatically hydrolyzed for potential use in a hypoallergenic infant formula. To assess the relative immunoreactivity of the hydrolysates, rabbits were immunized with either the intact proteins or the protein hydrolysates using a vigorous immunization protocol. Serum samples were tested using ELISA methods that quantitated IgG antibody specific for the immunizing protein hydrolysates and the corresponding intact proteins. The results showed that the protein hydrolysates had substantially lower immunogenicity than the parent proteins. Also, antibody specific for the parent protein showed very low cross-reactivity with the hydrolysates. Both of the protein hydrolysates seem to be promising candidates for use in hypoallergenic infant feeding systems.

The effect of the water activity of the milieu on rates of glucose uptake by the osmophilic yeasts Saccharomyces rouxii and Debaryomyces hansenii.

Rates of glucose uptake in baker's yeast and in the osmophilic yeasts D. hansenii and S. rouxii were investigated at different values of water activity of the milieu, as regulated either by glycerol or sodium chloride. In both cases, D. hansenii could maintain relatively higher rates of glucose uptake. At lower values of water activity, sodium chloride exerted an inhibitory effect on rates of glucose uptake by S. rouxii, while in the presence of glycerol, rates of glucose uptake shown by S. rouxii resembled those shown by D. hansenii. Rates of glucose uptake by baker's yeast were drastically affected at lower values of water activity in the presence of either solute. Lower values of water activity exerted a stimulatory effect on catalase activity of both S. rouxii and D. hansenii. However, activities of baker's yeast with regard to catalase and invertase were moderately affected under such conditions. Results presented may lead to the presumption that osmophilic yeasts, at least partly, have solved the problem of osmotic tolerance over nonosmotolerant strains by possessing a high capacity for maintaining higher rates of glucose uptake, in spite of the adverse external concentration of solute.