[Deep brain stimulation for hyperkinetic movement disorders]. / Tiefe Hirnstimulation bei hyperkinetischen Bewegungsstörungen.

The term hyperkinetic movement disorder encompasses dystonia, tremor, chorea, myoclon and tics. These symptoms are all caused by dysfunctional neural networks including the basal ganglia loop and can be accompanied by other neurological or psychiatric symptoms. Deep brain stimulation (DBS) is an important extension of therapeutic options for this group of patients in whom drug therapy is limited. Permanent electrodes are implanted in various subcortical brain areas in order to achieve an improvement in motor symptoms by high frequency stimulation. Already established indications include primary generalized or segmental dystonia and essential tremor but an increasingly better understanding of systemic pathophysiology has allowed DBS to be explored as a treatment for other disorders of the hyperkinetic spectrum. This article provides an overview of common hyperkinetic movement disorders from the viewpoint of recent advances in neurostimulation therapy.

[Deep brain stimulation. New target areas and new indications]. / Tiefe Hirnstimulation. Neue Zielgebiete und neue Indikationen.

Many patients with neurological movement disorders and psychiatric diseases cannot yet be adequately treated with conventional methods. Deep brain stimulation represents an important extension of therapeutic options by which invasive electrodes are implanted in various subcortical brain areas in order to achieve an improvement in motor and psychiatric symptoms by high frequency stimulation. Up to 2012 approximately 100,000 patients had been treated with deep brain stimulation worldwide. The indications for deep brain stimulation were essentially already established indications, such as idiopathic Parkinson's syndrome, dystonia and tremors. The newer indications which include in particular psychiatric symptoms, such as depression, obsessive diseases, addiction and Tourette syndrome, are as yet limited to approximately 5 % of treated patients. An increasingly better understanding of the system physiology of neurological and psychiatric diseases has promoted the search for new target areas and indications for treatment by neuromodulation. This article gives an overview of the latest developments in the established and also the developing application areas of deep brain stimulation.

Beta 2-adrenoceptor densities do not correlate with growth, carcass quality, or meat quality in cattle.

Drugs that activate beta 2-adrenoceptors (beta-agonists) are known to have profound effects on growth, body composition, and meat quality. Physiologically, these adrenoceptors are activated and regulated by the hormone adrenaline. Because the response to a drug or hormone is dependent partly on the density of the tissue receptors, the potential for predicting growth, carcass quality, or meat quality from knowing beta 2-adrenoceptor density in three disparate sample sites in cattle was examined. Cell membrane fragments were prepared using samples of longissimus muscle, semitendinosus muscle, or ear obtained within 30 min of death from 48 steers. Beta 2-Adrenoceptor density (Bmax) was measured in these membrane preparations by saturating them with the radioligand [125I]iodocyanopindolol. There was no correlation between Bmax values measured in ear samples, longissimus muscles, or semitendinosus muscles. Bmax measured in samples of ear did not correlate with any growth or carcass traits, including weight gain, carcass weight, fat depth, or eye muscle area. Bmax measured in longissimus muscle only correlated weakly with meat color, and Bmax measured in semitendinosus muscle only correlated with carcass weight. We conclude that beta 2-adrenoceptor density is not a useful predictor of growth, carcass quality, or meat quality in cattle.

Sexual dimorphism in the growth response of entire and gonadectomized rats to clenbuterol.

This study compared the anabolic effects of clenbuterol in male and female rats and determined the relative contribution of testicular and ovarian hormones to any observed gender difference. Seventy-two 12-wk-old rats were used in a 2 x 2 x 2 factorial design in which animals were either male or female, entire or gonadectomized at 3 wk of age, and fed either a control diet or a diet containing 4 mg clenbuterol/kg feed for 8 days. Compared with entire male rats, entire females gained 64% less weight, had lighter carcasses (-36%) and gastrocnemius muscles (-62%), and had higher plasma concentrations of the catabolic hormone corticosterone (P < 0.05). Castration had a negative effect on growth in male rats, and ovariectomy had a positive effect in females, but there was still a gender difference in body weight between gonadectomized males and females, which amounted to 34% of the gender difference observed in intact rats. The density of beta 2-adrenoceptors in skeletal muscle was not different between males and females, nor was it affected by gonadectomy. Clenbuterol increased both weight gain and gastrocnemius muscle weight, with the latter response in entire and castrated male rats (+ 1.31 and + 1.17 g) being more than double that seen in entire and ovariectomized females (+ 0.58 and + 0.55 g). The downregulation response of beta 2-adrenoceptors in this muscle was remarkably consistent in all treated groups (-50% to -53%).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of BRL-47672 on growth, beta 2-adrenoceptors, and adenylyl cyclase activation in female rats.

The morpholine compound BRL-47672 has a chemical structure similar to that of clenbuterol and causes similar anabolic effects in rats but has no actions on beta 2-adrenoceptors in vitro. It has been argued therefore that beta 2-adrenoceptors do not mediate the anabolic effects of this family of compounds. In the present study BRL-47672 was shown to bind to rat beta 2-adrenoceptors with low affinity (dissociation constant 16 microM) relative to clenbuterol (48 nM) and to be a very weak activator of adenylyl cyclase activity in rat skeletal muscle membranes in vitro. In contrast, acute administration of the drug to anesthetized rats in vivo caused an increase in muscle adenosine 3',5'-cyclic monophosphate output, and chronic treatment of conscious rats for > 6 days caused a significant increase in weight gain (69%) accounted for by increased muscle growth. The anabolic effects of BRL-47672 were not counteracted by daily injections of the drug ICI-118551 (2 mg/day) but were prevented when the same beta 2-antagonist was administered in the diet (200 mg/kg feed, equivalent to 4.3 mg/day). The beta 1-adrenoceptor selective antagonist CGP-20712A fed in the diet (200 mg/kg feed) failed to attenuate the response to BRL-47672. These results support the conclusion that BRL-47672 has little direct action on beta 2-adrenoceptors but suggest that the compound is metabolized rapidly in vivo to a potent beta 2-agonist. Thus the stimulation of muscle growth by BRL-47672 is via beta 2-adrenoceptors, with no contribution to this response from beta 1- or beta 3-adrenoceptor activation.

Characterization of LH and testosterone responses to intramuscular injection of GnRH in tropical postpubertal bulls.

Five Zebu x British crossbred bulls 17 months of age and of uniform liveweight (320+/-3 kg) were used to study testosterone responses to single intramuscular doses of exogenous gonadotropin-releasing hormone (GnRH). The eight dose levels used were 0, 31.25, 62.5, 125, 250, 500, 1000, and 2000 ng GnRH/kg live weight. Plasma samples for hormone responses were collected at 30-minute intervals from zero to three hours and at one-hour intervals from three to seven hours postinjection. Luteinizing hormone (LH) and testosterone responses were measured as peak heights or as areas under response curves. Increasing the dosage of GnRH increased the time to reach the peak LH response, the height and duration of the response, and the area under the response curve. The maximum LH peak height was reached by the 1 mug/kg dose. In contrast to LH, testosterone responses reached the same peak heights (two hours postinjection of GnRH) for all doses of GnRH. The only effect of increased dosage was to increase the duration of response. Testosterone responses showed repeatable differences (P<0.01) between animals, but LH responses did not. It was demonstrated that the testosterone status of bulls can be accurately assessed by simply measuring testosterone in a single plasma sample collected two to three hours after the intramuscular injection of 100 mug or more (dose unimportant) of GnRH per bull.