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).

Angiotensin-converting enzyme gene insertion/deletion polymorphism with metabolic syndrome in Turkish patients.

BACKGROUND: The ACE gene has received substantial attention in recent years as candidate for a variety of diseases. The most common polymorphism in ACE gene is the Insertion/Deletion (I/D, rs4646994) polymorphism located on intron 16. AIM: We investigated the association between metabolic syndrome (MS) and the insertion (I) - deletion (D) polymorphisms in the angiotensin converting enzyme (ACE) gene in south-east of Turkey. SUBJECTS AND METHODS: One hundred and sixty subjects, with 101 cases of MS and 59 age- and gender-matched healthy controls were included in the study. RESULTS: The frequency of ACE I/D polymorphism was found to be 49.5% for DD, 36.6% for ID, and 13.9% for II in the MSstudy group and 44.1% for DD, 42.4% for ID and 13.5% for II in the control group. Allele frequencies were found to be 0.68% for D and 0.32% for I allele in the study group with MS and 0.65% for D, 0.35% for I allele in the control group. The I/D polymorphism of the ACE gene, DD, ID, and II genotypes occurred with similar frequencies in the study group with MS and the control group with no significant differences (p<0.05). On applying one-way analysis of variance to different ACE gene polymorphic groups in patients with MS were not significantly associated to ACE gene polymorphism and waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HDL, and LDL (p<0.05). CONCLUSIONS: Further studies of patients in larger numbers and of different ethnic backgrounds may be necessary to elucidate the association between the ACE I/D gene polymorphism and MS.

The roles of Klotho and FGF-23 in bipolar manic episode.

OBJECTIVE: Bipolar disorder (manic episode) is an essential psychiatric disorder with unknown etiology, in which inflammation is considered to play a role. Klotho and FGF-23 are known to be associated with inflammation. Therefore, this study aimed to determine the link between Klotho and FGF-23 levels and bipolar disorder. PATIENTS AND METHODS: In this study, 42 men with BD and 41 healthy controls were enrolled, followed up, and/or treated at the High-Security Forensic Psychiatry Clinic. Sociodemographic data form, Young Mania Rating Scale, and Hamilton Depression Rating Scale were applied to all participants. RESULTS: Klotho and FGF-23 levels were significantly increased in patients with BD manic episodes. There was no correlation between Klotho and FGF-23 levels and clinical parameters. For Klotho and FGF-23, cutoff values of 69 and 1,646 yielded 67.4% sensitivity and 72.1% specificity and 81.4% sensitivity and 51.2% specificity, respectively. CONCLUSIONS: Klotho and FGF-23 may play critical roles in the etiopathology of manic episodes and are potential candidate biomarkers for bipolar disorder. This relationship might contribute to the etiopathogenesis of the disease and determine its treatment. Anti-Klotho and anti-FGF-23 administration may be a future treatment for controlling the course of the disease.

Takayasu arteritis and ulcerative colitis; coexistence or misdiagnosis?

Takayasu arteritis is a chronic inflammatory disease that primarily affects large arteries such as the aorta and its proximal branches. The association between Takayasu arteritis and ulcerative colitis is an extremely rare condition. Ulcerative colitis is an inflammatory bowel disease, clinical presentation is not specific and may mimic Crohn's disease, radiation colitis, ischemic colitis, a variety of infectious processes, and colitis related to medications. Herein we report a case of Takayasu arteritis who had been misdiagnosed and treated as ulcera-

Spontaneous intracranial hypotension after labor without spinal intervention.

We present a 29-year-old woman admitted with severe postural headache after spontaneous term labor. Lactation ceased for the duration of headache. Magnetic resonance imaging (MRI) revealed dural thickening that is suggestive of spontaneous intracranial hypotension. CT-cisternography disclosed cervicodorsal dural leak. She was treated with a high-volume epidural blood patch (EBP) and her symptoms were relieved. Lactation returned to normal after EBP. She had normal findings on follow-up MRI examination at 6 months.

Insulin resistance is not related to plasma homocysteine concentration in healthy premenapausal women.

This study was performed to test whether plasma homocysteine concentrations are related to insulin resistance in healthy premenopausal women. For this purpose, the relationship between insulin resistance (as assessed by HOMA index) and fasting plasma homocysteine level was determined in 83 healthy volunteers. The results indicated that homocysteine concentrations did not vary as a function of HOMA index (r = -0.147). Plasma homocysteine concentrations also did not vary as a function of other parameters of insulin resistance such as HDL-cholesterol and triglycerides, which they correlated inversely with body mass index (BMI). Furthermore, when individuals were classified according to quartiles of insulin resistance (HOMA index), plasma homocysteine concentrations from the lowest to the highest quartiles were not significantly different. On the other hand, the HOMA index correlated significantly with triglyceride concentrations (r = 0.377, p< 0.001), HDL-cholesterol (r = -0.310, p< 0.01) and BMI (r = 0.468, p< 0.001). These results suggest that plasma homocysteine concentrations are not related to insulin resistance and/or metabolic abnormalities associated with it in premenopausal women.

Primary angiosarcoma of the breast: Diagnosis with computer-assisted MRI-guided radio-guided occult lesion localization (ROLL) technique.

Primary angiosarcoma of the breast is a rare type of breast cancer that represents approximately 0.04% of all primary breast tumors. We report herein a case of primary breast angiosarcoma that was only visible on magnetic resonance imaging (MRI) examination. The patient presented with a palpable right breast lump that was not visible either on ultrasonography and mammography. MRI showed a lesion of the right breast that presented washout kinetics. MRI-guided biopsy allowed histopathological examination of the tumor that was further confirmed as primary angiosarcoma. Subsequently, MRI guided ROLL (radio-guided occult lesion localization) technique was used for localizing the lesion prior to surgery.

Subcellular localization and partial purification of prelamin A endoprotease: an enzyme which catalyzes the conversion of farnesylated prelamin A to mature lamin A.

The nuclear lamina protein, lamin A is produced by proteolytic cleavage of a 74 kDa precursor protein, prelamin A. The conversion of this precursor to mature lamin A is mediated by a specific endoprotease, prelamin A endoprotease. Subnuclear fractionation indicates that the prelamin A endoprotease is localized at the nuclear membrane. The enzyme appears to be an integral membrane protein, as it can only be removed from the nuclear envelope with detergent. It is effectively solubilized by the detergent n-octyl-beta-D-glucopyranoside and can be partially-purified (approximately 1200-fold) by size exclusion and cation exchange (Mono S) chromatography. Prelamin A endoprotease from HeLa cells was eluted from Mono S with 0.3 M sodium chloride as a single peak of activity. SDS-PAGE analysis of this prelamin A endoprotease preparation shows that it contains one major polypeptide at 65 kDa and smaller amounts of a second 68 kDa polypeptide. Inhibition of the enzyme activity in this preparation by specific serine protease inhibitors is consistent with the enzyme being a serine protease.

Regulation of prelamin A endoprotease activity by prelamin A.

The maturation of lamin A is completed by the endoproteolytic cleavage of its farnesylated precursor protein, prelamin A. In the absence of this cleavage, prelamin A can neither give rise to lamin A nor assemble into the nuclear lamina. We call the enzyme which catalyzes this endoproteolytic step the 'prelamin A endoprotease'. In this study, we begin characterization of the regulation of prelamin A endoprotease. In particular, we address the question as to whether prelamin A endoprotease activity is constitutive in cells or responds to expression of prelamin A. To do this, we compared the activity of this novel endoprotease in cells which express prelamin A with those that do not. Our data shows that the enzymatic activity of prelamin A endoprotease is enhanced by the expression of prelamin A.

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 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.

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.

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.

Vitamin C reduces cytochalasin D cataractogenesis.

The effect of cytochalasin D (CD), an actin monomer-stabilizer, has been studied on cataract development in rat lenses. Cataractogenesis was induced by incubating the rat lenses in medium 199 (M199) containing 10(-5) M CD; by the end of 24 h, lenses first developed a visible opacity. The increased lactate dehydrogenase (LDH) activity in the culture medium, leakage of lens cytosolic proteins into the culture medium and observable development of opacity through a dissection microscope were correlated with cell damage associated with cataract formation. Non-denaturing polyacrylamide gel electrophoresis was used to separate three lens LDH isoenzymes. The effect of 1 mM vitamin C (VC) in reducing LDH leakage was also examined. The protective effect of VC on CD-initiated cataractous lenses is significant. This suggest that a portion of the opacity and lens damage may involve oxidative damage to the membrane-cytoskeleton complex which is started by CD, but partially prevented by VC

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.

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.

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 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.

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.

Synthesis and in vitro calcium antagonist activity of 4-aryl-7,7-dimethyl/1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione derivatives.

In this study, a series of 4-aryl-7,7-dimethyl and 1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones (1-25) were synthesized by condensing urea or N-methylurea with 5,5-dimethyl-1,3-cyclohexanedione and appropriate aromatic aldehydes according to the Biginelli reaction. The structures of the compounds were confirmed by spectral data and elementary analysis. The calcium antagonist activity of the compounds was tested in vitro on isolated rat ileum and lamb carotid artery. Compounds 16 and 19 were the most active derivatives on isolated rat ileum compared with the standard nicardipine. On isolated aortic strips of lamb the calcium antagonist activity of compound 16 (maximum relaxant effect: 38.83+/-5.84%) was found as high as that of nicardipine (maximum relaxant effect: 35.50+/-4.16%) used as a reference drug.