Interaction Between Opioidergic and Dopaminergic Systems on Food Intake in Neonatal Layer Type Chicken

Central regulatory mechanisms for food intake regulation vary among animals. Evidence from animal studies suggests central opioids and dopamine have prominent role on appetite regulation but their interaction(s) have not been studied in layer-type chicken. Thus, in this study six experiments designed to investigate intracerebroventricular (ICV) administration of SCH23390 (D₁ like receptors antagonist), Sulpride (D₂ like receptors antagonist), DAMGO (μ-opioid receptors agonist), DPDPE (δ-opioid receptors agonist), U-50488H (κ-opioid receptors agonist) on feeding behavior in 3 h food deprived neonatal layer-type chickens. In experiment 1, chicks ICV injected with control solution, SCH23390 (2.5 nmol), DAMGO (125 pmol) and their combination (SCH23390 + DAMGO). In experiment 2: control solution, SCH23390 (2.5 nmol), DPDPE (δ-opioid receptors agonist, 40 pmol) and SCH23390 + DPDPE were applied to the birds. In experiment 3, injections were control solution, SCH23390 (2.5 nmol), U-50488H (30 nmol) and SCH23390 + U-50488H. In experiments 4–6 were similar to experiments 1–3 except Sulpride (2.5 nmol) applied instead of SCH23390. Then, cumulative food intake was recorded until 120 min after injection. According to the results, ICV injection of DAMGO (125 pmol) significantly decreased food intake but co-injection of DAMGO + SCH23390 diminished DAMGO-induced hypophagia (P < 0.05). Also, SCH23390 was not able to decrease the DPDPE- and U-50488H-induced hyperphagia (P > 0.05). Furthermore, Sulpride had no role on DAMGO, DPDPE and U-50488H-induced food intake (P > 0.05). These results suggest there is an interaction between opioidergic and dopaminergic systems via μ and D₁ receptors in appetite regulation in chicken.     

Novel plasma biomarker of atenolol-induced hyperglycemia identified through a metabolomics-genomics integrative approach

Introduction

While atenolol is an effective antihypertensive agent, its use is also associated with adverse events including hyperglycemia and incident diabetes that may offset the benefits of blood pressure lowering. By combining metabolomic and genomic data acquired from hypertensive individuals treated with atenolol, it may be possible to better understand the pathways that most impact the development of an adverse glycemic state.

Objective

To identify biomarkers that can help predict susceptibility to blood glucose excursions during exposure to atenolol.

Methods

Plasma samples acquired from 234 Caucasian participants treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses trial were analyzed by gas chromatography Time-Of-Flight Mass Spectroscopy. Metabolomics and genomics data were integrated by first correlating participant’s metabolomic profiles to change in glucose after treatment with atenolol, and then incorporating genotype information from genes involved in metabolite pathways associated with glucose response.

Results

Our findings indicate that the baseline level of β-alanine was associated with glucose change after treatment with atenolol (Q = 0.007, β = 2.97 mg/dL). Analysis of genomic data revealed that carriers of the G allele for SNP rs2669429 in gene DPYS, which codes for dihydropyrimidinase, an enzyme involved in β-alanine formation, had significantly higher glucose levels after treatment with atenolol when compared with non-carriers (Q = 0.05, β = 2.76 mg/dL). This finding was replicated in participants who received atenolol as an add-on therapy (P = 0.04, β = 1.86 mg/dL).

Conclusion

These results suggest that β-alanine and rs2669429 may be predictors of atenolol-induced hyperglycemia in Caucasian individuals and further investigation is warranted.

     

Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram-negative infection

The inflammatory response to Gram-negative infection was studied in LPS responder and nonresponder C3H mice. Twenty-four hours after ascending E. coli urinary tract infection, an influx of neutrophils into the urine was observed in C3H/HeN mice (Lpsn,Lpsn); no significant neutrophil influx occurred in C3H/HeJ mice (Lpsd,Lpsd) at this time. A second peak of urinary neutrophil excretion was observed in both strains of mice approximately 6 days post-infection. The first, but not the second peak was inducible by inoculation with formalin-killed E. coli but not by Gram-positive bacteria. This finding suggested that the first peak is triggered by LPS, whereas the second peak emanates from other bacterial components which activate both LPS responder and nonresponder mice. The first peak of the inflammatory response was inversely related to bacterial clearance. C3H/HeJ mice (Lpsd,Lpsd) retained about 2000-fold more E. coli in the kidneys than C3H/HeN mice (Lpsn,Lpsn). The infection persisted despite the late-occurring influx of neutrophils in C3H/HeJ mice. These results suggest that an inflammatory response to LPS is required for the elimination of a local Gram-negative infection.     

Polyelectrolyte effects on 9-aminoacridine-DNA binding

The 9-aminoacridine-DNA binding curve is analyzed in two ways: with polyelectrolyte effects neglected and with polyelectrolyte effects included. It is found that the analysis which includes polyelectrolyte effects is consistent with the violation of neighbor exclusion displayed by diacridine complexes as observed by Atwell et al. and by Zimmerman and coworkers. However the analysis which neglects polyelectrolyte effects is inconsistent with the diacridine results. This comparison supports the necessity of including polyelectrolyte effects in the analysis of drug-DNA binding curves.     

Ri-plasmid as a helper for introducing vector DNA into alfalfa plants

Genetic engineering of legumes and other important dicotyledonous plants is limited because of the difficulty of regenerating plants via cell culture. Since a considerable number of crop plants can be regenerated only from root culture, the introduction of foreign genes into Agrobacterium rhizogenes-induced hairy roots may expand the list of crop plants that could be genetically engineered. Here we report genetic transformation of alfalfa (Medicago sativa L.), a valuable forage legume, using a virulent strain of Agrobacterium rhizogenes containing, in addition to its Ri-plasmid, a binary vector containing a nopaline synthase gene. Plant cells transformed by this vector can be easily identified by their ability to produce nopaline. Transformed alfalfa plants were recovered from A. rhizogenes-induced hairy roots. These transgenic plants were characterized by normal leaf morphology and stem growth but a root system that was shallow and more extensive than normal. These plants were also fertile, set seeds upon self-pollination and outcrossing. Nopaline was detected in R1 progeny. Southern blot analysis confirmed the presence of multiple copies of T-DNAs from the Riplasmid in the plant genome in addition to the vector T-DNA.     

Influence of hormonal imprinting on hormone level. Permanent receptor damaging effect of pituitary hormones administered to newly-hatched cockerels

The overlapping effect of TSH and FSH on the gonad and on the thyroid gland can be demonstrated in cockerels even at the age of five weeks. These hormones influence the secretion of testosterone in a similar way and to a similar extent, while on the thyroxine level the influence of the specific hormone is more pronounced. Neonatal FSH and TSH treatment considerably decreased the basal testosterone level measured at the age of five weeks. Neonatal FSH treatment increased the basal T4 level while TSH treatment decreased it. The effect of TSH treatment administered at the age of five weeks in increasing the testosterone level was weakened after neonatal pretreatment with any iodine hormone. The effect of TSH treatment could only be inhibited by neonatal FSH pretreatment. Neonatal pretreatment with any of the trophormones caused a diminution of the T4 level augmenting of FSH and TSH administered at the age of five weeks.     

Interspecific protoplast fusion for the transfer of atrazine resistance from Solanum nigrum to tomato (Lycopersicon esculentum. L)

TAES Technical Article #23184     

Synergistic anticancer activity of valproate combined with nicotinamide enhances anti-proliferation response and apoptosis in MIAPaca2 cells

Histone deacetylase is strongly associated with epigenetic regulation and carcinogenesis, and its inhibitors can induce cell cycle arrest and apoptosis of the cancer cells. In this study we aimed to examine the antiproliferative effects a combination of the valproate with nicotinamide in MIAPaca2 cell line. We revealed that valproate acted in a synergistic/additive with nicotinamide to inhibit the proliferation and induction of apoptosis in MIAPaca2 cancer cell line. MIAPaca2 was treated with various concentrations of valproate. The MTT assay and colony formation in soft agar indicated that valproate at 0.5 mM, when used alone weakly, suppressed proliferation of cells (37 ± 3.02 %) whereas the combination treatment of valproate + nicotinamide significantly suppressed cell proliferation (58 ± 3.5 %). The effect of nicotinamide at 25 mM on cell proliferation and cell colonization induced 50 % apoptosis of MIAPaca2 cells. To identify the anti-proliferation and apoptotic effects of valproate and nicotinamide we performed flow cytometric and microscopic analyses. The results indicated significant apoptosis induction and nuclear morphological alterations greater than when valproate was used alone. Furthermore, western blot analyses was performed to study the role of acetyl-histone H3 levels, and quantitative RNA expression analyses were performed on expression of thrombospondin (TSP) and maspin genes in MIAPaca2. We found that the combination treatment of valproate + nicotinamide enhanced the expression of maspin and TSP genes and the biological response of the cell line was correlated with the increase of histone H3 acetylation after nicotinamide and valproate application. Together our findings indicate that valproate which act as inhibitor of cell proliferation and inducer of apoptosis in human cancer MIAPaca2 cells when used in combination with nicotinamide makes it a potentially good candidate for new anticancer drug development.     

Prevalence and detection of metallo-β-lactamase (MBL)-producingPseudomonas aeruginosa strains from clinical isolates in Iran

Of the 126 isolates obtained from clinical specimens, seventy strains were selected because of resistance or reduced susceptibilities to imipenem and/or ceftazidime. Screening for detection of MBL-producing strains was performed in latter isolates by the Etest MBL strips. Isolates that were positive to Etest MBL strips were analysed by PCR. PCR was performed with specific DNA probes for detection of genes coding IMP or VIM enzymes and positive controls (MBL-producing strains). Finally, eight isolates ofPseudomonas aeruginosa were detected to carry a bla_VIM gene.