The cells responsible for production of the male sex hormone testosterone, the Leydig cells of the testis, are post-mitotic cells with neuroendocrine characteristics. Their origin during ontogeny and regeneration processes is still a matter of debate. Here, we show that cells of testicular blood vessels, namely vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells. Resembling stem cells of the nervous system, the Leydig cell progenitors are characterized by the expression of nestin. Using an in vivo model to induce and monitor the synchronized generation of a completely new Leydig cell population in adult rats, we demonstrate specific proliferation of vascular progenitors and their subsequent transdifferentiation into steroidogenic Leydig cells which, in addition, rapidly acquire neuronal and glial properties. These findings, shown to be representative also for ontogenetic Leydig cell formation and for the human testis, provide further evidence that cellular components of blood vessels can act as progenitor cells for organogenesis and repair.

We studied 48 patients after bilateral subthalamic nucleus deep brain stimulation (STN‐DBS) who were evaluated 6 months after the surgical procedure using the Unified Parkinson's Disease Rating Scale (UPDRS) in a standardized levodopa test. Additional follow‐up was available in 32 patients after 12 months and in 20 patients after 24 months. At 6 months follow‐up, STN‐DBS reduced the UPDRS motor score by 50.9% compared to baseline. This improvement remained constant at 12 months with 57.5% and at 24 months with 57.3%. Relevant side effects after STN‐DBS included intraoperative subdural hematoma without neurological sequelae (n = 1), minor intracerebral bleeding with slight transient hemiparesis (n = 1), dislocation of impulse generator (n = 2), transient perioperative confusional symptoms (n = 7), psychotic symptoms (n = 2), depression (n = 5), hypomanic behaviour (n = 2), and transient manic psychosis (n = 1). One patient died because of heart failure during the first postoperative year. The current series demonstrates efficacy and safety of STN‐DBS beyond the first year after surgical procedure. Complications of STN‐DBS comprise a wide range of psychiatric adverse events which, however, were temporary. © 2003 Movement Disorder Society

Alterations of the nitric oxide receptor, soluble guanylate cyclase (sGC) may contribute to the pathophysiology of pulmonary arterial hypertension (PAH). In the present study, the expression of sGC in explanted lung tissue of PAH patients was studied and the effects of the sGC stimulator BAY 63-2521 on enzyme activity, and haemodynamics and vascular remodelling were investigated in two independent animal models of PAH.Strong upregulation of sGC in pulmonary arterial vessels in the idiopathic PAH lungs compared with healthy donor lungs was demonstrated by immunohistochemistry. Upregulation of sGC was detected, similarly to humans, in the structurally remodelled smooth muscle layer in chronic hypoxic mouse lungs and lungs from monocrotaline (MCT)-injected rats. BAY 63-2521 is a novel, orally available compound that directly stimulates sGC and sensitises it to its physiological stimulator, nitric oxide. Chronic treatment of hypoxic mice and MCT-injected rats, with fully established PAH, with BAY 63-2521 (10 mg?kg) partially reversed the PAH, the right heart hypertrophy and the structural remodelling of the lung vasculature.Upregulation of soluble guanylate cyclase in pulmonary arterial smooth muscle cells was noted in human idiopathic pulmonary arterial hypertension lungs and lungs from animal models of pulmonary arterial hypertension. Stimulation of soluble guanylate cyclase reversed right heart hypertrophy and structural lung vascular remodelling. Soluble guanylate cyclase may thus offer a new target for therapeutic intervention in pulmonary arterial hypertension.KEYWORDS: BAY 63-2521, cardiovascular diseases, nitric oxide, pharmacology, pulmonary arterial hypertension, smooth muscle P ulmonary arterial hypertension (PAH) is a disabling disease, with high mortality, characterised by sustained elevation in pulmonary arterial pressure (Ppa) and pulmonary vascular remodelling due to proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) [1]. Imbalance of vasodilatory and vasoconstrictive mediators has been implicated in these changes. Reduced urinary excretion of prostaglandin (PG)I 2 and augmented excretion of thromboxane metabolites were found in patients with idiopathic PAH (IPAH) [2], and immunohistological studies have shown reduced expression of PGI 2 synthase in the pulmonary vessels originating from those patients [3]. Another important mediator in the regulation of vascular tone is nitric oxide (NO), which is synthesised by NO synthases. Local NO production from endothelium and epithelium regulates pulmonary perfusion, depending on alveolar ventilation to assure optimised ventilation/perfusion distribution [4][5][6]. In patients with IPAH, it has been reported that the expression of endothelial NO synthase is downregulated [7], while other reports show an upregulation in plexiform lesions of IPAH patients [8]. However, little is known about the expression and regulation of soluble guanylate cyclase (sGC) which operates as a receptor for NO. Typically, sGC is found as a hetero...

The optimal stimulation site in subthalamic deep brain stimulation (STN-DBS) was evaluated by correlation of the stereotactic position of the stimulation electrode with the electrophysiologically specified dorsal STN border. In a series of 25 electrodes, best clinical results with least energy consumption were found in contacts located in the dorsolateral border zone, whereas contacts within the subthalamic white matter, e.g., zona incerta, were significantly less effective. We suggest that the dorsolateral STN border should be covered by STN-DBS.

R-(؊)-Deprenyl