Reduction of reticulata neuronal activity by zolpidem and alpidem, two imidazopyridines with high affinity for type I benzodiazepine receptors

Zolpidem and alpidem, two imidazopyridines with high affinity for the type I benzodiazepine recognition site, have recently been proposed as preferential hypnotic (zolpidem) and anxiolytic (alpidem) drugs notable for the minor incidence of side-effects. To further characterize the molecular mechanism involved in the action of these drugs, we studied their effects in comparison with those of diazepam on the spontaneous electrical activity of substantia nigra pars reticulata (SNR) neurons. These cells have been shown to be extremely sensitive to various positive and negative modulators of GABAergic transmission. All three drugs consistently produced a dose-dependent (0.03-8.0 mg/kg i.v.) inhibition of the firing of SNR cells when administered as a single bolus. However, zolpidem was more potent and efficacious than diazepam or alpidem. The ID50s were 0.076, 0.492 and 0.821 mg/kg, respectively. When the drugs were injected in exponentially (ratio 2) increasing doses up to 8.0 mg/kg, the rank order for tachyphylaxis was zolpidem much greater than diazepam greater than alpidem. Since the effects of the drugs were abolished and prevented by a small dose (0.5 mg/kg i.v.) of flumazenil (Ro 15-1788), it is likely that the effects were mediated through activation of benzodiazepine receptors. The results indicate that the hypnotic, zolpidem, has a more potent inhibitory action on SNR cell activity than the anxiolytics, alpidem and diazepam.     

A modified algorithm for the management of ureteral calculi: 100 consecutive cases

We treated 100 consecutive ureteral calculi requiring intervention with a previously described algorithm. There were 16 ureteropelvic junction, and 18 upper, 22 mid and 44 lower ureteral calculi. Treatment was by a stent and extracorporeal shock wave lithotripsy in 10 ureteropelvic junction, 10 upper ureteral and 3 mid ureteral calculi, ureteroscopy and extracorporeal shock wave lithotripsy in 6 upper and 6 mid ureteral calculi, and ureteroscopy alone in 5 ureteropelvic junction, 2 upper and 12 mid ureteral calculi. All 44 lower ureteral calculi were treated successfully by ureteroscopy. Of the 100 patients studied 98 were treated by endourological methods (extracorporeal shock wave lithotripsy or ureteroscopy), while 2 required an operation (1 with a ureteropelvic junction calculus and 1 with a mid ureteral calculus). Over-all, 100 patients required a total of 125 procedures to accomplish successful stone removal. An algorithm is developed in which lower ureteral calculi are treated by ureteroscopy, mid ureteral calculi (large and dense) by stent bypass and extracorporeal shock wave lithotripsy or (lucent and fragile) by ureteroscopy, upper ureteral calculi by stent bypass and extracorporeal shock wave lithotripsy without manipulation, and impacted ureteral stones initially by ureteroscopy and, if necessary, then by extracorporeal shock wave lithotripsy.     

Primary tangential excision for hand burns

The article describes the correct technique of primary tangential excision in deep dermal and third-degree hand burns. The operation performed under tourniquet facilitates the preservation of viable tissue, which is of utmost importance in hand burns. The therapeutic results depend on the extent of destroyed tissue. Primary tangential excision prevents fibrosis due to prolonged infection and impaired circulation, thus creating much more favorable conditions for reconstruction and rehabilitation.     

Differences in the kinetic properties and sensitivity to inhibitors of human placental, erythrocyte, and major hepatic aldehyde dehydrogenase isoenzymes

(i) The characteristics of the major human hepatic isoenzymes of aldehyde dehydrogenase (ALDH), ALDH I and ALDH II, were compared with the ALDH activities found in human placenta and erythrocytes, (ii) In human liver biopsies, the Km of ALDH I was approximately 7 mumol/L whereas it was 32 mumol/L for ALDH II. The Vmax for ALDH I was 2-3 times greater than the ALDH II Vmax. Human liver ALDH I and II also differed in their sensitivity in inhibitors. Namely, ALDH I was less sensitive to disulfiram than the ALDH II isoenzyme. (iii) ALDH activity in human placenta and erythrocytes was much lower than in liver tissue. Kinetic data showed that placental ALDH isoenzyme had a high Km (in the millimolar range) and increased its activity raising the pH from 7.4 to 8.8, more than the hepatic ALDH I and ALDH II isoenzymes did. Erythrocyte ALDH activity presented a dual component; the smaller one was characterized by a low Km (micromolar range), whereas most of the ALDH activity showed a high Km (millimolar range). (iv) Placental ALDH was resistant to nitrefazole inhibition and was inhibited by disulfiram in a manner similar to the hepatic ALDH I isoenzyme; erythrocyte ALDH was more sensitive to the inhibitory action of disulfiram and nitrefazole. (v) It is concluded that erythrocyte and placental ALDH isoenzymes are different from the hepatic ALDH I and ALDH II forms. It is also suggested that placental and erythrocyte ALDH isoenzymes are different high-Km isoenzymes.     

Levodopa up-regulates platelet alpha 2-adrenoceptors

Treatment of dogs for 21 days with oral levodopa (100 mg b.i.d.) plus benserazide (25 mg b.i.d.) induced a significant increase in the number of platelet alpha 2-adrenoceptors labelled by [3H] yohimbine with no change in Kd. The rise was maximal at the end of the treatment and remained significant during the month following the cessation of treatment. Plasma catecholamine levels did not vary. Competition experiments showed a low affinity of both dopamine and levodopa for platelet alpha 2-adrenoceptors. These results suggest that levodopa treatment regulates alpha 2-adrenoceptor number in dog platelets.     

The effect of thymosin fraction 5 and its synthetic component thymosin-alpha 1 on rat open-field behavior

The effect of thymosin fraction 5 and its synthetic component thymosin-alpha 1 administered i. p. and i. c. v. on the behavior of 219 Wistar rats in the open field was studied to establish the effective dose and time of action of both substances. It was shown that at i. c. v. administration of both compounds in a dose of 10 ng the motor activity was suppressed for about 0.5 hour. At i. p. administration thymosin fraction 5 in doses of 0.15, 0.3 and 0.6 mg/kg suppressed the motor activity for more than 2 hours. The higher the dose, the greater the degree of suppression of the motor activity. Both peptides influence in a similar way the motor activity of the animals irrespective of the route of administration.     

Reduction using an immunomodulator of the level of respiratory infections in chronic bronchitis

Fifty-six patients with recurrent bronchopulmonary infections associated with chronic bronchitis were randomly allocated to 2 groups, to assess whether treatment with an immunomodulator, Diribiotin CK, could enhance resistance to infection. The double-blind, placebo-controlled prospective trial over a 9 month period showed that this immunomodulator was well tolerated and significantly reduced the rate of respiratory tract infection. The drug also significantly reduced the prescribing of antibiotic medication and the rate of absenteism from work. These effects have been demonstrated in a rigorously designed clinical study. This is the first time that a clear clinical activity has been attributed to an inducer of soluble mediators of immunity.