The effects and mechanisms of the action of galangin on spatial memory in rats.

BACKGROUND: Galangin, a flavonoid compound with acetylcholinesterase inhibitory activity, may improve cognitive functions by enhancing cholinergic transmission. OBJECTIVES: We aimed to investigate the effects of galangin on spatial memory impairment in rats. METHODS: The effects of galangin (50 and 100 mg/kg) and reference anti-dementia drug donepezil (1mg/kg) administrations were examined on memory impairment induced by the muscarinic cholinergic receptor antagonist scopolamine or the nicotinic cholinergic receptor antagonist mecamylamine in the Morris water maze (MWM) test. Hippocampal acetylcholine concentrations were also determined. RESULTS: Galangin 50 and 100 mg/kg significantly decreased the mean distance to platform and increased the time spent in the escape platform quadrant in scopolamine-treated rats. Galangin 100 mg/kg significantly decreased the mean distance to platform and increased the time spent in the escape platform quadrant in mecamylamine-treated rats. The effects of galangin in the MWM were comparable with donepezil. Scopolamine and mecamylamine decreased acetylcholine concentrations, whereas galangin both alone and with mecamylamine or scopolamine administration increased acetylcholine concentrations. CONCLUSION: Galangin improved memory impairment comparable to donepezil and nicotinic and muscarinic receptors may be involved in this effect. Galangin may be considered as a promising flavonoid in the prevention and treatment of memory impairment in Alzheimer's disease and other dementias (Fig. 7,Ref. 37).

The effects of verapamil on stress- and histamine-induced gastric lesions in rats.

The influence of verapamil on stress-induced and histamine-induced gastric ulcers was investigated in rats. The influence of verapamil was also examined on various biochemical parameters that affect the development of these ulcer models. The animals were pretreated with intraperitoneal verapamil (1, 5, 25 mg/kg) by injection 1 h before the induction of experimental ulceration. The gastric lesions were induced by cold-restraint stress or intraperitoneal injection of histamine (300 mg/kg). The gastroprotective effects of verapamil were evaluated by determining the ulcer index, gastric mucus content, free and total acidity, lipid peroxidation and non-protein sulfhydryl content. Verapamil pretreatment at a dose of 25 mg/kg significantly reduced stress-induced ulcers. Verapamil enhanced mucus secretion, reduced total acidity and lipid peroxidation and decreased non-protein sulfhydryl content in a dose-dependent fashion. On the other hand, pretreatment with verapamil at any dose had no significant effect on histamine-induced ulcers. L-Arginine (L-A) (100 mg/kg) or L-nitroarginine (L-NNA) (100 mg/kg) were also injected i.p. to the animals 1 h before stress to test the role of nitric oxide (NO) in the mechanism of the gastroprotective activity of verapamil (25 mg/kg). The results suggested that verapamil stimulates gastric NO production, but the overproduction of NO worsens gastric ulcers. The effects of verapamil on experimentally induced ulcers may be related to its ability to induce biochemical alterations in the parameters measured in gastric tissue.

The effects of vitamin E in ovalbumin-sensitized guinea pigs.

It has been suggested that epithelium destruction, mucus secretion, edema and bronchoconstriction may play a role in asthma pathogenesis. Additionally, histamine, serotonine, leukotrienes and other mediators are released and free oxygen radicals are produced during bronchoconstriction. We studied the role of antioxidants on the treatment of asthma by testing alpha-tocopherol (vitamin E; 5, 25, 50 and 100 mg/kg/day i.p.), a scavenger of oxygen radicals, on male Guinea pigs. The animals were sensitized by injecting ovalbumin. After sensitization, isolated tracheal preparations were studied in vitro. The effects of carbachol 10(-4) M, ovalbumin 10(-3) M and vitamin E (10(-5) M, 10(-4) M, 10(-3) M concentrations) were evaluated in an isolated organ bath. It was observed that alpha-tocopherol reduced the contractile effects of ovalbumin and carbachol. The 5, 25 and 50 mg/kg/day doses of vitamin E were injected intraperitoneally to Guinea pigs that were sensitized with ovalbumin. We observed significant differences between the contractile responses to carbachol and vitamin E with carbachol. These treatments significantly reduced the contractility of tracheal preparations (p < 0.001). There was no significant difference with the 100 mg/kg/day i.p. dose of vitamin E in the contractile response to carbachol E (p > 0.05). The upper part of the tracheal preparations was the most sensitive region to the contractile effect of 10(-3) M ovalbumin in all groups (p < 0.001). The contractile response to 10(-3) M ovalbumin was reduced by 25 and 50 mg/kg/day doses of vitamin E (p < 0.001).

The synthesis of some triazolylphenothiazine derivatives and their antidepressant and anxiolytic activities.

10-[2-(4-Amino-5-mercapto-1,2,4-triazol-3-yl)ethyl]phenothiazine was prepared starting from 3-(10-phenothiaziniyl)propionic acid. This new triazole was employed in the synthesis of some Schiff bases and N-bridged heterocycles. All the newly synthesized compounds were characterized by analytical, IR, 1H-NMR and MASS Spectral studies. Some of the newly synthesized compounds were screened for their antidepressant and anxiolytic activities.

The effects of fusidic acid on the inflammatory response in rats.

In the present study the antiinflammatory activity of fusidic acid was investigated in a model of formalin-induced edema formation in rats. Fusidic acid at doses of 50 and 100 mg kg (-1) was administered p.o. to rats for ten days. It was observed that fusidic acid inhibited edema formation significantly (P< 0.05). After this period, gastric mucus secretions were evaluated by the Alcian blue dye binding method. Mucus secretion decreased significantly in the control group. Fusidic acid increased the amount of gastric mucus. Moreover, in all of the animals with paw edema, platelet count was also increased. Red blood cell count, haemoglobin concentration and haematocrit were all higher in the control group than those of the fusidic acid groups. The present observations suggest that fusidic acid suppressed the inflammatory response and stimulated the gastric mucus secretion and it prompts further experiments for delineation of the mechanism of these actions as well as clinical trials.

Synthesis of some triazolyl-antipyrine derivatives and investigation of analgesic activity.

The synthesis of some triazolyl-antipyrine derivatives starting from 4-chloroacetamidoantipyrine and 3-(aryloxyalkyl)-4-ethyl/phenyl-5-mercapto-1,2,4-triazoles is described. The chemical structures of the compounds were elucidated by IR, 1H-NMR and mass spectral studies. These compounds were tested for analgesic activity.

4-aryl-6,6-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones: synthesis, chromatographic resolution and pharmacological activity.

In this study, a series of 4-aryl-6,6-dimethyl-1,2,3,4,5,6,7,8- octahydroquinazoline-2,5-diones were synthesized by condensing urea with 4,4-dimethyl-1,3-cyclohexanedione and appropriate aromatic aldehydes according to the Biginelli reaction. The structures of the compounds were characterized by spectroscopic methods. The racemic compounds were resolved into the enantiomers by HPLC on amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD). The compounds were tested in vitro for their calcium antagonistic activities. BaCl2-induced contractions of rat ileum were inhibited dose-dependently. Compounds 3 and 5 exerted weak calcium antagonistic activity on smooth muscles compared with the standard, nicardipine.

Morning-evening administration time differences in digoxin kinetics in healthy young subjects.

Digoxin, frequently used in the treatment of congestive heart failure, has a very narrow therapeutic index. We studied the differences in digoxin pharmacokinetics when ingested in the morning versus evening. A single digoxin (0.25 mg) dose was given orally to the same group of 10 diurnally active healthy (6 male and 4 female) volunteers in the morning at 08:00 and evening at 20:00 in separate experiments scheduled 2 weeks apart. Blood samples were collected at specific times for 48h after each timed dose; digoxin was determined by radioimmunoassay (RIA). Maximum plasma concentration Cmax; Tmax, the time to reach Cmax; area under plasma concentration curve AUC; and elimination half-time T1/2 of digoxin were determined. Tmax was statistically significantly shorter (54 min) following 08:00 dosing com pared to 20:00 dosing (96 min). Although the Cmax was higher after morning than evening dosing, it was not significantly so. No other parameter of digoxin pharmacokinetics except Tmax exhibited administration time dependency.

Serum leptin levels in type 1 diabetic and obese children: relation to insulin levels.

OBJECTIVES: To compare serum leptin levels in type 1 diabetic and obese children. DESIGN AND METHODS: We studied serum leptin levels in 35 type 1 diabetic, 32 obese, and 35 healthy children. Seven of 35 were new-onset diabetics with ketoacidosis. C-peptide (CPE) levels were used for estimating insulin secretion. RESULTS: Serum leptin levels were lower in diabetics than in controls (p<0.001). Obese children had higher leptin and CPE levels than diabetics and controls. In new-onset diabetics, 1 month insulin treatment did not cause any change in leptin levels (p>0.05). Leptin was correlated positively with body mass index and CPE (p<0.001) and inversely with glucose (p = 0.001) and HbA1c (p<0.05) in the combined group. HbA1c and gender were the independent predictors of leptin in diabetic children (p<0.01). CONCLUSIONS: Low serum leptin levels in type 1 diabetic children may be due to chronic insulin deficiency related with their metabolic control. Leptin and insulin may have complementary roles in maintaining a stable body weight.

Synthesis of some thiazolyl-pyrazoline derivatives and preliminary investigation of their hypotensive activity.

Some 1-(4-arylthiazol-2-yl)-3,5-diaryl-2-pyrazoline derivatives were synthesized by reacting 1-thiocarbamoyl-3,5-diaryl-2-pyrazoline derivatives with phenacetylbromide in ethanol. The structural elucidation of the compounds were performed by IR, 1H-NMR and Mass spectral data and elemental analyses. The hypotensive activities of 13 compounds were evaluated by using the tail-cuff method. All examined compounds showed appreciable hypotensive activities. Clonidine was used as reference substance in the pharmacological evaluation.

Breast milk leptin concentrations in initial and terminal milk samples: relationships to maternal and infant plasma leptin concentrations, adiposity, serum glucose, insulin, lipid and lipoprotein levels.

Leptin has recently been shown to be present in human milk and is produced by mammary epithelial cells. We studied leptin concentrations in human milk and its relationships with maternal and infant plasma leptin concentrations, adiposity, serum glucose, insulin, lipid and lipoprotein levels. We also compared the initial and terminal milk leptin concentrations to investigate whether leptin acts as a satiety factor. Venous blood samples were obtained from 18 healthy lactating women aged from 17-42 years and their 3-120 day-old infants. Breast milk samples were collected just before and immediately after suckling, when the infant had self-terminated sucking. Leptin mean values in breast milk were lower than in maternal plasma (p<0.001). Breast milk log leptin concentrations positively correlated with both maternal and infant plasma log leptin concentrations (p<0.001 and p=0.001, respectively) and negatively correlated with maternal serum total cholesterol and low-density lipoprotein cholesterol levels (p<0.001 and p<0.01, respectively), but did not correlate with maternal and infant adiposity, serum glucose and insulin levels, maternal serum HDL-C, triglyceride levels and infants' lipid and lipoprotein concentrations (p>0.05). Using stepwise multiple regression analysis, maternal plasma log leptin and serum HDL-C concentrations were related to breast milk log leptin concentration (R2=0.82; p<0.0001 and p<0.001, respectively). There was no significant difference between initial and terminal milk leptin levels (p>0.05). We concluded that maternal leptin may be transferred to the infant via milk and may exert biological effects; there may be factors other than adiposity affecting breast milk leptin levels, and that leptin might not contribute to the development of satiation at the end of suckling.

Cord blood leptin levels: relationship to body weight, body mass index, sex and insulin and cortisol levels of maternal-newborn pairs at delivery.

To investigate leptin and to which factors it is related during the perinatal period, we measured serum leptin levels of 46 mothers at delivery, umbilical cord blood and infants on the third day of life. Maternal leptin was higher than in cord (p < 0.001), and did not correlate with maternal age, body weight, body mass index, weight gain during pregnancy, serum glucose, cholesterol, triglycerides, CPE, cortisol or HbA1c levels, nor any biochemical values or anthropometric data of the newborns (p > 0.05). In cord blood, leptin was significantly higher than in 3 day-old infants (p < 0.05), and correlated only with maternal insulin and glucose (r = 0.5, p < 0.01 and r = 0.4, p < 0.05, respectively). In 3 day-old infants, leptin did not correlate with any clinical data (p > 0.05). Leptin was not different in the two sexes (p > 0.05). Serum leptin levels were not related to adiposity of the mother-infant pairs or neonatal growth, and were not different in the two sexes during the perinatal period.

Synthesis and analgesic activity of some triazoles and triazolothiadiazines.

The synthesis of some triazoles and triazolothiadiazines starting from (5,6,7,8-tetrahydronaphthalen-2-yl)oxyacetic acid is described. The chemical structure of the compounds were elucidated by analytical, IR, 1H NMR and mass spectral studies. Some of the newly synthesized compounds were tested for analgesic activity and compounds 5b, 5c, and 5d exhibited promising analgesic activity.

Serum leptin levels during childhood and adolescence: relationship with age, sex, adiposity and puberty.

We studied serum leptin levels in 189 healthy children to evaluate related factors during childhood and adolescence. Leptin correlated with body mass index (BMI), triceps skinfold thickness (p<0.001) and body weight (p<0.01). Obese children and girls had higher leptin levels than non-obese children and boys, respectively (p<0.001). In girls, leptin correlated positively with age, skinfold thickness and BMI (p<0.001). In boys, leptin correlated negatively with age (p<0.001) and positively with skinfold thickness (p<0.05). Prepubertal boys had higher leptin levels than prepubertal girls and pubertal boys (p<0.05). Pubertal girls had higher leptin levels than prepubertal girls and pubertal boys (p<0.001). Leptin levels in girls were higher at Tanner stages 4 and 5 than at stage 1 (p<0.001). In conclusion, serum leptin levels are related with adiposity, have obviously age-related gender differences during childhood and adolescence, and may be involved in the maturation of reproductive capacity.

Synthesis and vasodilatory activity of some thiazolo-triazole derivative.

In this study, some thiazolo[3,2-b]-1,2,4-triazole derivatives were synthesized. Their vasodilatory activities were examined in vitro. All examined compounds showed appreciable activity.