The effect of oral and subcutaneous meperidine on the maximal electroshock seizure (MES) in mice.

The likely effect of oral and subcutaneous meperidine on maximal electroshock seizure (MES) in mice was studied. Convulsive current fifty (CC50) was assessed to be 46m A, an electrical pulse causing seizure in 50% of test animals. Doses of 15, 30, 60, or 120 mg/kg meperidine given orally or subcutaneously increased the convulsion threshold of MES as evidenced by a significant dose-dependent reduction of MES below control value (p < .05). An initial hyperactivity reaction that was worsened by noisy and tactile stimuli and tail erection followed by sedation was observed after s.c. injection of 60 or 120 mg/kg meperidine. No significant difference was found between meperidine-induced reductions of control MES values obtained one and two hours after oral doses; the depressed MES values obtained one hour after oral administration of meperidine were significantly different and more powerful than those obtained two hours after s.c. drug administrations (p < .05). Combining previous literature information with the present results, we conclude that such an effect of meperidine can be attributed to cerebellar stimulation.

The role of mast cells in the genesis of acute manifestations following the intravenous injection of meperidine in dogs.

The effects of intravenous (iv) administration of the synthetic opioid analgesic meperidine in conscious dogs and their relation to histamine stored in mast cells were studied in comparison with those induced by compound 48/80, potent mast cell degranulator. When 48/80 (0.5 mg/ kg) and meperidine (10 mg/kg) were injected iv into conscious dogs, an acute brief period of yelling, flare reaction, scratching, hypersalivation, urination, defecation, and tachypnea occurred after a latency of 30-35 sec. In addition, meperidine-treated dogs showed marked sedation. Dogs whose histamine stores were depleted by 48/80 manifested none of those effects induced by meperidine except sedation. Likewise, pretreatment with meperidine prevented the effects of a subsequent injection of 48/80. Sedation appeared to be independent of the histamine-releasing effect of meperidine, whereas other effects elicited by its intravenous injection of the drug were suppressed by 48/80 and thus were probably mediated via released histamine. We concluded that the peripheral effects of meperidine show histamine dependency and mast cells are a potential important site for the peripheral actions of meperidine as well.

The stability of choline ascorbate.

The stability of choline ascorbate was studied considering concentration, temperature, and pH of the drug solution. Our results revealed that choline ascorbate is almost fully stable with respect to these parameters. Practically no loss was observed when 3 x l0(-1) (50%) drug solution is preserved in the refrigerator, at ambient temperature, or at 37 degrees C for one year, a finding that favors the high stability of this compound. Choline ascorbate was also found to be more stable in comparison to vitamin C and crystalline ascorbic acid. Its dilution within a vitamin B solution did not modify the amount of ascorbic acid within 120 min at ambient temperature. We conclude that the choline ascorbate form of ascorbic acid appears to be more reliable and promising when the quality of therapy with this agent is concerned.

Application of the Sherman-Morisson formula to scattering problems by multi-component systems.

The scattering matrix for multi-component systems is recalculated using the extended form of the Sherman-Morisson formula. The matrix elements are given explicitly in closed form. The Gibbs-Duhem relation separates the density and composition contributions.

Response to intradermal injection of monosodium urate crystals in Behçet's syndrome.

The cutaneous response to intradermal injection of monosodium urate crystals was investigated in 97 patients with Behçet's syndrome in Turkey and 14 in the United Kingdom, and in 82 healthy and 88 diseased controls. Urate crystals produced an increased erythematous response in patients compared with controls in both countries. This response was different from that of the pathergy test performed at the same time. The systemic acute phase response, studied only in Turkey, showed no differences between patients and controls.

The influence of choline ascorbate on the blood levels of ascorbic acid in humans.

Our study has clearly shown that the oral administration of choline ascorbate, which contains approximately 500 mg of ascorbic acid to the volunteers causes an increase in the blood levels of ascorbic acid. This increase is statistically significant (p less than 0.01) compared with the basal level each time. In the control group, vitamin C tablet also causes an increase in the blood level of ascorbic acid. However, this increase is less than that of the test group. Our results indicate that ascorbic acid, as a part of choline ascorbate molecule, reaches the blood circulation without losing its activity.

The effect of propranolol on maximal electroshock seizures in mice.

The aim of this study was to determine the possible effect of propranolol, a beta-adrenoceptor blocker, on maximal electroshock seizures (MES) in mice. It was found that doses of 5, 10 and 20 mg/kg propranolol caused an increase in the convulsion threshold of maximal electroshock seizures (MES) proportional to the dose and, that the mode of the anticonvulsant action of propranolol used doses in this study is related to membrane stabilization.

The effect of naloxone on the blood level of morphine and histamine in morphine perfused dogs.

Injection of naloxone to morphine perfused naive dogs caused a transient increase in the blood level of morphine although no concomitant increase in the blood level of histamine was observed. The increase in the blood level of morphine following naloxone administration was statistically significant (p less than 0.001) within the 1st min and decreased rapidly to control values by 10 min. A second injection of naloxone administered 2 h later did not increase the blood level of morphine. Similarly, administration of naloxone to morphine perfused dogs pretreated with compound 48/80, a potent mast cell depleter, revealed no increase in the blood level of morphine. These findings indicate that morphine was promptly bound to the mast cells after perfusion and the origin of morphine released into the blood by naloxone was the mast cells.

The effect of naloxone on the blood levels of morphine and histamine in morphine dependent dogs.

Naloxone administration to morphine dependent dogs has caused an increase in the blood level of morphine, which was transient and statistically significant up to 1 min following the injection of the drug, although concomitant increase in the blood histamine level was not observed. Subsequent injection of naloxone has failed to produce an increase in the blood level of morphine. Likewise, injection of naloxone to morphine dependent dogs pretreated with compound 48/80, a potent mast cell depleter, revealed no increase in the blood level of morphine. This was attributed to the fact that, the origin of morphine, released into the blood, was the mast cells.

Use of ornidazole in fractionated radiotherapy: dose tolerance, serum and tumour tissue concentration.

Sensitizing and neurotoxic effect of ornidazole, was tested in a double-blind randomized study in patients with carcinoma of the cervix and larynx. Ornidazole or placebo were given orally, two times weekly, for 3 weeks. Dose was 2.5 g/m2 for each administration. Total dose given was 15 g/m2. Radiation therapy was given 3 h after the drug administration. Ornidazole was well tolerated in the majority of the patients. No neurotoxic side effects, such as peripheral neuropathy or convulsion, were observed with a total dose of up to 30 g. Dizziness, somnolence and nausea were the prominent acute side effects, seen mostly (70%) in women. In the placebo group this rate was 17% (p less than 0.01). No important side effect was observed in men receiving ornidazole. Serum concentration of ornidazole reached the maximum level in 2-4 h after oral administration and ranged (23 patients) from 65.1 to 139.8 micrograms/ml. Mean half-life was 15.6 +/- 2.8 h. Peak concentration in tumour tissue was achieved 1-3 h after the administration, ranging from 13.0 to 78.0 micrograms/g. Tumour concentration of ornidazole ranged from 14 to 93% of the serum concentration at the time of irradiation.

The release of morphine from the mast cells by 48/80 in morphine perfused dogs.

The aim of this study was to determine whether or not mast cells store or bind morphine. Injection of a potent mast cell depleter, compound 48/80 to dogs, 10 minutes after completion of a perfusion of 30 mg/kg of morphine produced a large concomitant increase of both morphine and histamine in blood samples drawn from the aorta. This increase is transient and statistically significant up to 1 minute following the injection of the drug. Morphine and histamine levels decrease rapidly as they reach the general circulation and are subjected to distribution. Injection of compound 48/80 one hour after the end of the morphine perfusion produces a less prominent increase in morphine and histamine levels. In both instances, subsequent doses of compound 48/80 failed to produce any increase in the levels of morphine or histamine. All these findings strongly indicate that in these dogs, the increase in morphine levels following 48/80 injection is caused by a release of morphine, bound or stored in the mast cells of the lungs, during the course of the perfusion.

The effect of compound 48/80 on the precipitated withdrawal syndrome of dogs.

The aim of this study was to eliminate endogenous stores of histamine before inducing the precipitated withdrawal syndrome. Results demonstrate that histamine plays a role in the emergence of some of the symptoms which characterize the precipitated abstinence syndrome in morphine-dependent dogs. Morphine-dependent dogs receiving 0.5 mg/kg n-allyl-normorphine exhibit the precipitated abstinence syndrome. Injection of compound 48/80, 0.5 mg/kg, a potent histamine liberator, produced, on the other hand, typical signs of the abstinence syndrome. A second injection of this compound 24 hours later, however, failed to induce these signs. An injection of n-allyl-normorphine also failed to induce these signs in dogs pretreated with compound 48/80 despite the fact that the dogs were still on their morphine regime. Control experiments on naive animals showed that injection of 0.5 mg/kg n-allyl-normorphine failed to produce signs of the abstinence syndrome. Injection of compound 48/80, a potent histamine liberator, on the other hand, did produce the typical signs of the abstinence syndrome. Animals pretreated with n-allyl-normorphine followed by compound 48/80 responded similarly to animals treated with compound 48/80 alone.

The effects of compound 48/80 on the fibrinolytic activity of dogs.

It has been demonstrated that histamine by itself, did play some role in the activation mechanism of fibrinolysis. In this particular work, it was demonstrated that histamine at doses not affecting blood pressure levels, did not exert any direct immediate effect on fibrinolytic activity. Compount 48/80, a powerful mast cell depleter and histamine liberator, by itself, has no direct molecular effect on fibrinolytic activity, but rather, through the release of activators and/or inhibitors form mast cells, will exert either an activating or inhibiting action, according to the dose used. Low doses, such as 0.2 mg/kg i.v. will achieve a higher degree of activator release, while doses of 1.0 mg/kg will result in higher inhibitors release from mast cells.

Distribution of taste thresholds for phenylthiocarbamide among different age groups in Turkey.

The relation between age and taste threshold in populations living both in Istanbul and Resadiye, a town located in eastern part of Turkey, was investigated. In Turkey the nontaster/taster ratio has been found lower than in the other countries of Europe and Asia (3 ,4 ,8 ,9). With aging the taste sensitivity of tasters does diminish. However, the differences in the taste threshold levels of nontasters, in different age groups, have been found as being statistically not significant.