Effect of vitamin E treatment on the oxidative damage occurring in Henoch-Schönlein purpura.

AIM: To evaluate the role of reactive oxygen molecules (ROMs) in the pathogenesis of Henoch-Schönlein purpura and the effect of vitamin E on oxidative damage. ROMs have been suggested to contribute in many pathological conditions including renal diseases and vasculitis. METHODS: The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as antioxidant enzymes were measured, and the level of malondialdehyde (MDA) as an indicator of lipid peroxidation in 27 children with Henoch-Schönlein purpura at the onset of the disease and during the remission period. The results of this study were compared with those of 11 healthy children studied as a control group. RESULTS: With regard to all the oxidative damage parameters such as SOD, GSH-Px and MDA, significant differences were detected between the patients and the control group in both the acute and remission periods. But no such differences were detected between patients with and those without renal involvement. In 15 patients receiving vitamin E treatment, oxidative damage parameters and clinical course showed no improvement despite significant increases in plasma vitamin E levels. CONCLUSION: Oxidative damage and lipid peroxidation may play an important part in the pathogenesis of Henoch-Schönlein purpura but vitamin E given after initiation of lipid peroxidation, which is the last phase of cellular damage, is of no use in breaking down the oxidative chain reactions that have already been triggered.

Effects of neomycin on the development of tolerance to morphine antinociception.

The effects of neomycin on the development of tolerance to morphine antinociception were examined in mice. Because neomycin did not readly cross blood brain barrier, we examined the effects of neomycin following systemic, intracerebroventricular (i.c.v.) and intrathecal (i.t.) injections on the morphine tolerance. Daily subcutaneous (s.c.), i.c.v. and i.t. injections of morphine produced tolerance regardless of route of administration. Both i.c.v. and i.t. neomycin, which alone produced no changes in the basal tail flick latencies, significantly attenuated the development of tolerance to antinociception produced by repeated systemic morphine, while intraperitoneal (i.p.) administration of neomycin did not affect morphine tolerance. Further, i.c.v. and i.t. neomycin attenuated the development of tolerance to antinociception produced by repeated i.c.v. and i.t. morphine, respectively, which were not attenuated by systemic neomycin. This results indicate a potential role for neomycin-sensitive Ca2+ channels on the development of tolerance to the morphine antinoception.

Malondialdehyde, glutathione peroxidase and superoxide dismutase in peripheral blood erythrocytes of patients with acute cerebral ischemia.

The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD-1) were measured in the red blood cells (RBC) of 34 patients with acute ischemic hemispheric stroke on the first and seventh day after their stroke onset, and compared with 30 control individuals matched for sex, age and stroke risk factors. Within the first 24 h after stroke, SOD and GSH-Px activities were significantly decreased and MDA levels were significantly elevated in the patients compared with control subjects. Decrease in SOD and GSH-Px activities and increase in MDA levels showed significant correlation with infarct size, initial stroke severity assessed by NIH stroke scale and poor short-term prognosis. Observed changes in the RBC oxygen scavenging process returned to values not different from those of control subjects within seven days after stroke. Our results indicated that antioxidant enzyme concentrations decreased below normal levels in the acute period following ischemic stroke. Until the recovery of antioxidant defence mechanisms, which occurred up to seven days after stroke onset according to our results, the use of neuroprotective therapy against oxyradical injury seems reliable.

Correlation between lead exposure indicators and sister chromatid exchange (SCE) frequencies in lymphocytes from inorganic lead exposed workers.

Inorganic lead exposure was studied in 31 volunteers employed in storage battery plant. The genotoxicity of lead was measured in terms of sister chromatid exchange (SCE). Erythrocyte delta-aminolevulinic acid dehydrogenase (ALAD) activity, urinary delta-aminolevulinic acid (U-ALA), and blood lead levels (PbBs) were also determined to evaluate some possible relations between these lead exposure indicators and the observed SCE frequencies. Blood lead concentration of 36.31 microg/dl was determined as an average level in the workers. Consequently decreased ALAD activity in erythrocytes and increased U-ALA excretion was observed in statistically higher PbBs when compared with the control group. A statistically significant correlation was observed between the PbBs and SCE frequencies (p < 0.05). Moreover, the correlation between U-ALA excretion and SCE frequencies (p < 0.01) was relatively higher than the correlation between PbBs and SCE frequencies. These results might indicate a possible mechanism of ALA mediation in the genotoxic effects of lead.

Oxidative stress and nitric oxide related parameters in type II diabetes mellitus: effects of glycemic control.

OBJECTIVES: The aim of this study is to investigate the status of oxidative stress and nitric oxide related parameters in type II diabetes mellitus (DM) patients in which heart disease, atherosclerosis, retinopathy, and nephropathy commonly occur, and also to determine the effect of glycemic control on these parameters. DESIGN AND METHODS: Erythrocyte copper zinc-superoxide dismutase (CuZn-SOD), erythrocyte and plasma selenium dependent glutathione peroxidase (Se-GPx), erythrocyte catalase (CAT) activities, erythrocyte and plasma thiobarbituric acid reactive substances (TBARS) levels; nitrite/nitrate (NO(2)(-)/NO(3)(-)), cyclic guanosine monophosphate (cGMP) and nitrotyrosine levels in plasma of type II DM patients were measured. RESULTS: Erythrocyte CuZn-SOD activities in type II DM were significantly higher than those of the control subjects (p < 0.05). TBARS levels in type II DM were significantly higher than the control subjects (p < 0.001). Plasma NO(2)(-)/NO(3)(-) levels in type II DM patients both during poor glycemic control and after three months of oral antidiabetic treatment were significantly higher than those of the control subjects (p < 0.001). Plasma cGMP levels in type II DM patients during poor glycemic control were significantly lower than those of control subjects (p < 0.001). CONCLUSION: These results indicate that oxidative status and nitric oxide metabolism are affected in type II DM patients. We found high CuZn-SOD activity in type II DM patients. This increased activity could not protect the patients against the reactive oxygen species (ROS), since lipid peroxidation (defined by erythrocyte and plasma TBARS levels) still occurs in DM patients. After the therapy with oral antidiabetic agents for three months, erythrocyte SE-GPx and CAT activities were found to be decreased below the control values. Our results suggested that the low cGMP levels in the study may be a good marker of endothelium dysfunction in DM.

Dissolution properties of different designed and formulated salbutamol tablet dosage forms.

Pharmaceutical availability or in vitro availability is one of the aspects of drug bioavailability. Dissolution can be described best as a tool that can provide valuable information about the availability of a drug product. Dissolution test was performed on three different designed and formulated of salbutamol tablet formulations marketed in Turkey. The test methods were the paddle method and the rotating basket method described in United States Pharmacopeia. All studied formulations showed a good agreement with pharmacopeial requirements. In particular all studied commercial tablet formulations showed a quite fast release of the antiasthmatic drug. Other type of table formulations showed slow release. In order to evaluate the dissolution rates five different kinetics have been examined and the best fitting kinetics was found to be RRSBW kinetic.

Clarithromycin targeting to lung: optimization of the size, morphology and release characteristics of albumin microspheres.

Micropheres are drug carrier system which ensures controlled release in the shape of solid sphere particles with variable diameter distributions from a few microns to a milimeter of size. The active substance is dispersed in molecular level or in forms of macroscopic particles. Clarithromycin was selected as the model active substance in our study. Clarithromycin microspheres were prepared and evaluated by an emulsion polymerization technique. Two matrix materials have been considered as the basis in preparing the selected model active substance. Natural human serum albumin and bovine serum albumin, which were frequently used in early microsphere studies and are being used in some studies as microshpere matrix material were used. Albumin microspheres containing clarithromycin were prepared by heat stabilization at different stirring rate. In the first part of our study, drug content, payload, particle size, surface morphology and release characteristics from microspheres prepared.

Defective antioxidant defense system in patients with a human leptin gene mutation.

Antioxidant defense system prevents the organism from the detrimental effects of free radicals via scavenging or inhibiting their formation. Changes in the antioxidant defense mechanisms and alterations of several essential trace elements in both plasma and various tissues of ob/ob mice have been reported previously. Recent finding of the restoration of the defective antioxidant enzyme activity after leptin treatment in ob/ob mice suggests a putative role of leptin in modulation of antioxidant enzyme activity. Therefore, the aim of this study was to investigate whether antioxidant enzymes and trace elements could also be altered in patients with leptin gene mutation. Seven patients (five men and two women, two of them are homozygous and 5 are heterozygous) with leptin gene mutation and 31 healthy, sex- and age-matched and non-related to the patients (24 male and 9 female), control volunteers were enrolled in the study. Plasma and erythrocyte glutathione peroxidase (GSH-Px) and erythrocyte copper-zinc superoxide dismutase (CuZn-SOD) activities were measured spectrophotometrically. Plasma selenium (Se), manganese (Mn), zinc (Zn), copper (Cu), and iron (Fe) levels were measured by atomic absorption spectrophotometry. Mean Cu and Fe levels in patients were not significantly different than those in controls whereas mean Se, Zn and Mn levels were significantly lower in patients than those of controls (P=0.007, P=0.001, and P=0.001, respectively). Erythrocyte GSH-Px (39%), plasma GSH-Px (24%) and erythrocyte CuZn-SOD activities (32%) were significantly lower than those of the control group (P=0.001, P=0.002, P=0.001, respectively). In conclusion, our results demonstrate that the activity of antioxidant enzymes and plasma levels of Se, Zn and Mn levels were decreased in both homozygous and heterozygous subjects with leptin gene mutation. We suggest that both leptin and trace elements might be involved in the modulation of antioxidant defense system.

Clarithromycin targeting to lung: characterization, size distribution and in vivo evaluation of the human serum albumin microspheres.

Microspheres of clarithromycin have been prepared from human serum albumin using the emulsion polymerization technique. Albumin microspheres containing the active substance were injected into the tail vein of mice. Mice were sacrificed at intervals and microspheres collected from lungs and livers. The clarithromycin amount in microspheres was determined by reversed phase high performance liquid chromatographic (HPLC) method from the mice organs. Morphological and histopathological observations were also reported. The microsphere accumulation began at 10 min, and increased gradually until 6 h, then a decrease was observed. The microspheres were still present after 24 h. In the liver sample, no microsphere accumulation was observed at any time.

Improvement of water solubility and in vitro dissolution rate of gliclazide by complexation with beta-cyclodextrin.

Inclusion complexes of gliclazide with beta-cyclodextrin were prepared using different two methods: neutralization and recrysstalization. Host-guest interactions were studied in the solid state by X-ray diffractometry and infrared spectroscopy. The stability constant between gliclazide and beta-cyclodextrin was calculated from the phase solubility diagram. It was found that the neutralization technique and a solid complex of gliclazide with beta-cyclodextrin in a molar ratio of 1.5:1 could be used to prepare the amorphous state of drug inclusion complexes. The dissolution rates of gliclazide from the inclusion complex made by neutralization was much faster than the pure drug, physical mixture of drug and cyclodextrin, recyristalization system and also comparable to the data reported in literature. Results of this report indicate that beta-cyclodextrin could be useful for the solid gliclazide formulations as it may results in a more rapid and uniform release of the drug.

Effects of agmatine on ethanol withdrawal syndrome in rats.

Effects of agmatine, which is an endogenous polyamine metabolite formed by decarboxylation of L-arginine, have been investigated on the ethanol withdrawal syndrome in rats. Adult male Wistar rats were used in the study. Ethanol (7.2% v/v) was given to the rats by a liquid diet for 21 days. Agmatine (20, 40, 80 and 160 mg/kg) and saline were injected to rats intraperitoneally 30 min before ethanol withdrawal testing. After 30th min, 2nd and 6th h of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, stereotyped behavior, wet dog shakes and tremor were recorded or rated. A second series of injections was given at 6 h after the first one, and subjects were then tested for audiogenic seizures. Agmatine caused dose-dependent and significant inhibitory effects on stereotyped behaviors, wet dog shakes and tremors during the observation period. It did not cause any significant change in motor coordination of naive (not ethanol-dependent) rats. Our results suggest that agmatine attenuates withdrawal syndrome in ethanol-dependent rats; thus, this drug may be beneficial in the treatment of ethanol dependence.

Enhanced release of solid dispersions of etodolac in polyethylene glycol.

This work examines the release of etodolac from various molecular weight fractions of polyethylene glycol (PEG) solid dispersions. Solid dispersions of etodolac were prepared in different molar ratios of drug/carrier by using solvent and melting methods. The release rate of etodolac from the resulting complexes was determined from dissolution studies by use of USP dissolution apparatus 2 (paddle method). The physical state and drug:PEG interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction (XRD), infrared spectroscopy (IR) and differential scanning calorimetry (DSC). The dissolution rate of etodolac is increased in all of the solid dispersion systems compared to that of the pure drug and physical mixtures. The solid dispersion compound prepared in the molar ratio of 1:5 by the solvent method was found to have the fastest dissolution profile. The physical properties did not change after 9 months storage in normal conditions.

Iodine and zinc, but not selenium and copper, deficiency exists in a male Turkish population with endemic goiter.

Although endemic goiter has been shown to have a high prevalence in Turkey, little is known about the concentration of urinary iodine, plasma selenium (Se), copper (Cu), and zinc (Zn) in these patients. We studied on 140 male patient with endemic goiter (mean age: 22.2 +/- 0.19 yr) and 140 healthy male subjects (mean age: 21.8 +/- 0.28 yr). Daily urinary iodine excretion was determined by the ionometric method. Plasma Se, Zn, and Cu were determined by using atomic absorption spectrometry. Daily urinary iodine excretion was found to be significantly lower in the patient group (38.7 +/- 2.26 microg/d) than that of controls (50.73 +/- 2.56 microg/day, p = 0.001). Plasma Zn concentrations were also found to be significantly lower in the patient group (1.04 +/- 0.03 microg/mL) than that of controls (1.16 +/- 0.02 microg/mL, p = 0.001). No significant difference was determined in Se and Cu concentrations between the patient and control groups. Our study shows that a moderate iodine deficiency exists in both patients with endemic goiter and control subjects, which indicates the important role of iodine deficiency in the etiopathogenesis of endemic goiter in Turkey. Zinc deficiency may also contribute to the pathogenesis of endemic goiter. However, Se and Cu do not seem to have any role in the etiopathogenesis of endemic goiter in Turkey. A community-based iodine fortification program throughout the country may be proposed to take over the problem, which also can prevent the contributing effects of other element deficiencies that occur when iodine deficiency is the prevailing factor.

Aluminum content of vaccines used in Turkey.

Aluminum salts have been used in the preparation of a number of vaccines, toxoids, and allergen injectants as an adjuvant for many years. Although aluminum allergy is rare, there are many reported cases caused by aluminum-precipitated vaccines or hyposensitization therapy. Therefore, determination of the aluminum content of these vaccines is necessary information regarding adverse reactions related to these vaccines. In the present study, the aluminum contents of several vaccines (n = 19) routinely used in Turkey were, determined by electrothermal atomic absorption spectrophotometry. We found that aluminum levels in the vaccines ranged from 0.0 to 1438 mg/L.

Beneficial effect of thyrotropin-releasing hormone on neuropathy in diabetic rats.

Thyrotropin releasing hormone (TRH) is therapeutically effective in experimental and clinical spinal injury. The effects of TRH on diabetic neuropathy are not known. The aim of the present study was to investigate the electrophysiological effects of TRH in the streptozotocin diabetic rats. Three groups of rats were studied, non-diabetic control (n = 10), diabetic controls (n = 8), and TRH treated diabetic rats (n = 9). Administration of TRH or saline and electrophysiological measurements were performed 4 weeks after induction of diabetes. TRH was given intraperitoneally in a dose of 600 microg (3 ml). Nerve conduction velocity (NCV), measured in caudal nerve, and N1 latency of somatosensory evoked potentials (SEP) were measured 75 min after injection of TRH or serum saline. SEP latencies were 28.1 +/- 0.6, 29.4 +/- 0.8, 27.8 +/- 1.1 ms, in normal, diabetic and diabetic TRH-treated groups, and NCV values were 28.1 +/- 0.8, 23.8 +/- 0.4, and 27.9 +/- 0.7 m/s respectively. NCV was significantly reduced in the diabetic group compared to normals (P < 0.05). but then improved by TRH treatment (P < 0.05). Our findings suggest that TRH has an acute effect on peripheral neuropathy in experimental streptozotocin diabetes in the rat.

Noradrenaline and nitrite-nitrate concentrations in the contralateral testes during ipsilateral spermatic cord torsion in the presence or absence of a testis and epididymis.

OBJECTIVE: To determine the changes occurring during ipsilateral spermatic cord torsion either in the presence or absence of the ipsilateral testis and epididymis, by evaluating noradrenaline and nitrite-nitrate concentrations in the contralateral testes. MATERIALS AND METHODS: Forty male albino rats were allocated randomly to one of four equal groups undergoing: group 1, a sham operation; group 2, ipsilateral spermatic cord torsion; group 3, epididymo-orchidectomy only; and group 4, spermatic cord torsion after epididymo-orchidectomy. The contralateral testes were harvested after 24 h and the noradrenaline and nitrite-nitrate contents determined. The levels in each group were compared using the Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: The noradrenaline content of testes from group 2 was significantly lower than in those of groups 1 and 3, but there were no significant differences in content between groups 1 and 3, 1 and 4, and 2 and 4. The content in group 4 was significantly less than that in group 3. There were no significant differences in nitrite-nitrate contents among any of the groups. CONCLUSION: Spermatic cord torsion for 24 h, either in the presence or absence of a testis and epididymis, significantly decreased the noradrenaline content in the contralateral testis. This finding supports the suggestion that the sympathetic system is activated by exposure to noradrenaline in the contralateral testis during ipsilateral spermatic cord torsion, with no dependency on the presence of a testis and epididymis. As the nitrite-nitrate concentrations were unaffected, nitric oxide seems to have no role in contralateral testicular deterioration.

In vitro corrosion behaviour and microhardness of high-copper amalgams with platinum and indium.

Samples prepared from Luxalloy, GS-80, Permite-C and Logic and polished after 24 h by traditional methods were stored in polypropylene tubes containing phosphate-buffered saline solutions (pH 3.5 and 6.5) and distilled water. The amounts of mercury, silver, tin, copper, zinc, platinum and indium in the test solutions were determined at the first, second, eighth, 52nd and 78th week by atomic absorption spectrometry. At the end of the eighth week the amalgam samples were removed from solutions and evaluated by Rockwell Super Scial Microhardness tester. Statistically significant low amounts of metal ions were measured for Permite-C containing indium and Logic containing platinum. The microhardness test results showed that there were statistically significant increases in the microhardness of Permite-C and Logic. As a result it was shown that the amalgam samples were affected from corrosion conditions to different degrees. Sample of the Logic group that was stored in distilled water, showed smoother surface properties than other amalgam samples containing high copper. However, it was observed that samples of Permite-C group had the smoothest surface properties.

Dihydropteridine reductase activity and neopterin levels in leukemias and lymphomas: is there any correlation between these two parameters?

Urinary neopterin levels, blood dihydropteridine reductase activity as well as other frequently used clinical parameters were evaluated in 110 patients suffering from various types of lymphomas and leukemias. Among them neopterin was detected as the most sensitive marker representing the severity of malignancy (p<0.00001). All patients with active diseases had significantly raised urinary neopterin levels compared to those in remission and healthy controls. Of 69 patients with active disease 66 (96%) were above the upper limit seen in healthy subjects. In addition, the highest neopterin excretion was found in patients with active chronic myeloid leukemia (1469+/-479 micromol/mol creatinine n=16). In contrast, only 1 of 41 patients in stable responsive disease and remission (2.4%) had increased urinary neopterin levels above the upper limit. Dihydropteridine reductase (DHPR) activities were also detected in all patients and control groups. In active disease slightly reduced (DHPR) activities were evident (3.42+/-0.37 for controls, 2.92+/-0.39 in active disease and 3.28+/-0.42 nmol red cytochrome C/min/5 mm diameter disc in remission patients). However in patients under medication this was strengthened. This data also suggest that DHPR activity can be effected by chemotherapy. The results of the present study support the fact that urinary neopterin levels may be an useful and reliable early prognostic marker for neoplasia when used together with other prognostic indicators. Our data also suggest that reductions in DHPR activities may also be an underlying cause for the neurological disorders that are commonly seen in patients with haematological malignancies.

Synthesis and antinociceptive activity of some 3-substituted benzothiazolone derivatives.

Thirteen 3-substituted benzothiazolone derivatives have been synthesized. Their chemical structures have been elucidated by IR and NMR spectral data and by elemental analyses. Among these compounds, 1-¿3-[2(3H)-benzothiazolon-3-yl[propanoyl]morpholine (5b); 1-¿3-[2(3H)-benzothiazolon-3-yl[propanoyl]-4-benzylpiperidine++ + (5c); 1-¿3-[2(3H)-benzothiazolon-3-yl[-propanoyl]-4-phenylpiperazine (5d); 3-[3-(4-benzylpiperidine-1-yl)propyl]-2(3H)-benzothiazolone (5k); 3-[3-(4-benzylpiperazine-1-yl)propyl]-2(3H)-benzothiazolone (5I); 3-[3-(4-phenylpiperazine-1-yl)propyl]-2(3H)-benzothiazolone (5m) have been found to be significantly more active than the others.

The aluminum content in some patch test allergens.

The Al content of 18 patch test allergens were measured by electrothermal atomic absorption spectrophotometry. It was found that these preparations contained Al in various amounts. We conclude that the presence of Al in patch test allergens may interfere with the diagnosis and evaluations of patients to whom the test is applied.