Sami Aydin

3,4-Diaminopyridine and choline increase in vivo acetylcholine release in rat striatum

We investigated the effects of choline, 3,4-diaminopyridine and their combination on acetylcholine release from the corpus striatum of freely moving rats which were treated or not with atropine. Intraperitoneal administration of choline or intrastriatal administration of 3,4-diaminopyridine increased acetylcholine levels in striatal dialysates in a dose-dependent manner. When 3,4-diaminopyridine treatment was combined with choline, the observed effect was considerably greater than the sum of the increases produced by choline or 3,4-diaminopyridine alone. Administration of atropine (1 microM) in the dialysing medium was also found to be effective to stimulate striatal acetylcholine levels. 3,4-Diaminopyridine did not affect acetylcholine levels under these conditions. Whereas the choline-induced increase in acetylcholine release was significantly potentiated by atropine, co-administration of 3,4-diaminopyridine with choline failed to produce a further significant increase in the presence of atropine. These results suggest that a highly effective means for increasing acetylcholine release involves two concurrent treatments that increase neuronal choline levels and inhibition of the negative feedback modulation of acetylcholine release.

Vitamin a deficiency in patients with common variable immunodeficiency.

Vitamin A, a naturally occuring antioxidant micronutrient, has immunomodulating effect in patients with immunodeficiency, including an influence on cytokine production and lymphocyte growth and functions. Vitamin A deficiency is associated with a shift from type 2 cytokines to predominantly type 1 cytokines. The aims of this study were to determine Vitamin A status in Common variable immunodeficiency (CVID) patients and the relationship between Vitamin A status and cytokines production. Serum Vitamin A, neopterin, TNF-alpha, IL-2, IL-4, and IL-10 levels were determined in 19 CVID patients and 15 healthy children. Effects of 9-cis retinal, Vitamin A derivative, on cytokines (TNF-alpha, IL-2, IL-4 and IL-10) production in lymphocytes were tested in vitro condition using lymphocyte cultures obtained from CVID patients and healthy children.Serum Vitamin A level in CVDI patients was, 21.1± 1.5 μg/dL, significantly (p < 0.001) lower than the value, 35.7± 1.8 μg/dL, observed in healthy children. Serum neopterin level in the patients was, 9.8± 2.9 nmol/L, higher (p < 0.05) than the value, 3.9± 0.7 nmol/L, observed in control group. Common variable immunodeficiency patients, serum IL-4 level was significantly (p < 0.05) lower than the value observed for healthy children. Serum TNF-alpha, IL-2 and IL-10 levels were similar in the patients and healthy children. Vitamin A derivative, 9-cis retinal, increased TNF-alpha and IL-4 production in cultured mononuclear cells obtained from control and CVID patients. Vitamin A derivative, also, increased IL-2 and Il-4 production in cultured mononuclear cells obtained from CVID patients.These results show that CVID patients have low serum Vitamin A levels and high serum neopterin levels. A supplementation with Vitamin A may have role in downregulation of inflammatory responses in CVID patients.

The mediation of the central histaminergic system in the pressor effect of intracerebroventricularly injected melittin, a phospholipase A2 activator, in normotensive rats

Melittin is a polypeptide component of bee venom that leads to an increase in arachidonic acid release and subsequently in prostaglandin synthesis by activating phospholipase A(2). Recently we demonstrated that centrally or peripherally administrated melittin caused pressor effect and central thromboxane A(2) (TXA(2)) and cholinergic system mediated these effects of melittin. Also centrally injected histamine leads to pressor and bradycardic response by activating central histamine receptors in normotensive rats and central cholinergic system involved the effects of histamine. The present study demonstrates an involvement of the central histaminergic system in melittin-induced cardiovascular effect in normotensive rats. Experiments were carried out in male Sprague Dawley rats. Intracerebroventricularly (i.c.v.) injected melittin (0.5, 1 and 2 nmol) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR) as we reported previously. Moreover, H(2) receptor antagonist ranitidine (50 nmol; i.c.v.) almost completely and H(3)/H(4) receptor antagonist thioperamide (50 nmol; i.c.v.) partly blocked melittin-evoked cardiovascular effects, whereas H(1) receptor blocker chlorpheniramine (50 nmol; i.c.v.) had no effect. Also centrally injected melittin was accompanied by 28% increase in extracellular histamine concentration in the posterior hypothalamus, as shown in microdialysis studies. In conclusion, results show that centrally administered melittin causes pressor and bradycardic response in conscious rats. Moreover, according to our findings, there is an involvement of the central histaminergic system in melittin-induced cardiovascular effects.

Investigation of serum amino acid and serum amyloid A concentrations in chickens with amyloid arthropathy

Background: Increased proteolytic cleavage of serum amyloid A (SAA) may potentially contribute to the development of AA amyloid deposition Objective: To study the possible relationship between amyloid artropathy and expression of SAA and some serum amino acids. Animals and methods: Values of 15 serum amino acids and SAA were investigated in chickens with experimentally induced amyloid arthropathy. Thirty-four, 5-week-old chicks were allocated into two groups: one group was injected intra-articularly with 0.25 mL complete Freunds adjuvant at the left tibio-metatarsal joint to induce amyloid arthropathy, whereas the other group served as control. All pullets were necropsied 13 weeks after injection. Collected tissue samples were examined histopathologically. Blood samples were collected and SAA concentrations were measured with enzyme-linked immunosorbent assay. High-performance liquid chromatography was used to assess the amino acid concentrations in serum. Results: Amyloid accumulation in joints occurred only in the experimental group (89%). SAA concentrations of 166 ± 17 and 423 ± 39 (SD) ng/mL were found in the control and experimental groups, respectively (p < 0.001). In the experimental group, an increase was observed in all examined amino acid concentrations except for citrulline. The most significant (p < 0.001) increases were noticed in serine (from 159 ± 15 to 360 ± 29 µmol/L), glycine (from 151 ± 20 to 279 ± 16 µmol/L), isoleucine (from 48 ± 2 to 80 ± 6 µmol/L), and phenylalanine (from 49 ± 2 to 90 ± 3 µmol/L). Conclusion: The results of this study suggest that there is a positive correlation between some serum amino acid values, especially serine, glycine, isoleucine, and phenylalanine, and the high concentrations of SAA in chickens with amyloid arthropathy.

The effect of Gly–Gln [ß-endorphin30–31] on morphine-evoked serotonin and GABA efflux in the nucleus accumbens of conscious rats

Glycyl-L-glutamine (Gly-Gln; β-endorphin30-31) is an endogenous dipeptide synthesized through the post-translational processing of β-endorphin1-31. Central Gly-Gln administration inhibits the rewarding properties of morphine and attenuates morphine tolerance, dependence and withdrawal although it does not interfere with morphine analgesia. In an earlier study, we found that Gly-Gln inhibits morphine-induced dopamine efflux in the nucleus accumbens (NAc), consistent with its ability to inhibit morphine reward. To further investigate the mechanism responsible for its central effects we tested whether i.c.v. Gly-Gln administration influences the rise in extracellular serotonin and GABA concentrations evoked by morphine in the NAc. Conscious rats were treated with Gly-Gln (100nmol/5μl) or saline i.c.v. followed, 2min later, by morphine (2.5mg/kg) or saline i.p. and extracellular serotonin and GABA concentrations were analyzed by microdialysis and HPLC. Morphine administration increased extracellular serotonin and GABA concentrations significantly within 20min, as shown previously. Unexpectedly, Gly-Gln also increased extracellular serotonin concentrations significantly in control animals. Combined treatment with Gly-Gln+morphine also elevated extracellular serotonin concentrations although the magnitude of the response did not differ significantly from the effect of Gly-Gln or morphine, given alone suggesting that Gly-Gln suppressed morphine induced serotonin efflux. Gly-Gln abolished the morphine-induced rise in extracellular GABA concentrations but had no effect on extracellular GABA when given alone to otherwise untreated animals. These data show that Gly-Gln stimulates NAc serotonin efflux and, together with earlier studies, support the hypothesis that Gly-Gln inhibits the rewarding effects of morphine by modulating morphine induced dopamine, GABA and serotonin efflux in the NAc.

Serum choline levels in patients with stable angina and acute coronary syndromes: relation to the severity of coronary artery disease.

ObjectiveWe sought to investigate whether serum choline levels are increased across the spectrum of coronary artery disease (CAD) manifestations and correlate with the severity of coronary stenosis. MethodsA total of 36 patients with acute coronary syndrome (ACS) [22 patients with non-ST-segment elevation ACS and 14 patients with ST-segment elevation acute myocardial infarction (STEMI)], 22 patients with stable angina pectoris (SAP), and 18 controls were recruited for the study. In ACS patients, serum choline levels were measured on admission, and at 24 and 48 h thereafter, using high-performance liquid chromatography. The severity of CAD was assessed using the Gensini score. ResultsSerum choline levels on admission were significantly higher in the entire group of patients with ACS than in controls. The highest level of choline was observed in the STEMI group, followed by the SAP, and the non-ST-segment elevation ACS groups. Serum choline levels decreased gradually in patients with STEMI over the 48-h period. Serum choline levels on admission, and at 24 or 48 h thereafter, did not correlate with the presence of CAD neither in patients with ACS (P=0.78, 0.98 and 0.98, respectively) nor in those with SAP (P=0.92). ConclusionOur results suggest that serum choline levels are increased in ACS patients. However, there was no clear correlation between levels of choline and the severity and extent of CAD in this patient group.