Relationship between testosterone deficiency and cardiovascular risk and mortality in adult men

Classic male hypogonadism is associated with known adverse effects including decreased libido, erectile dysfunction, osteoporosis, and changes in body composition. Recently, we have come to appreciate that reduction in serum testosterone (T) levels resulting from aging or chronic disease or androgen deprivation therapy (ADT) have consequences similar to those seen in classic male hypogonadism which include increased fat mass, decreased lean body mass, decreased muscle strength, and sexual dysfunction. These data suggest that low T levels may represent a newly recognized cardiometabolic risk factor. Therefore, we carried out a careful review of the literature, focusing on major turning points of research and studies which gave more important and controversial contribution to the cardiovascular role of T. Observational studies and clinical trials investigating the relationship between T levels and cardiovascular disease and mortality were identified byMedline search. The results were synthesized, tabulated, and interpreted. The aim of this review is to discuss the association between low T levels and adverse metabolic profile such as insulin resistance, metabolic syndrome, and diabetes. We will also investigate the potential mechanisms by which male hypogonadism, especially age related or induced by ADT, may increase cardio-metabolic risk. Finally we will detail the emerging relationship between low T and mortality in men addressing also the reverse hypothesis that low T has a protective role by turning off T-dependent functions.     

RNA quality control and protein aggregates in amyotrophic lateral sclerosis: A review

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. The biologic basis of ALS remains unknown. However, ALS research has taken a dramatic turn over the past 4 years. Ground breaking discoveries of mutations of genes that encode RNA processing proteins, and demonstration that abnormal aggregates of these and other proteins precede motor neuron loss in familial and sporadic ALS, have initiated a paradigm shift in understanding the pathogenic mechanisms of ALS. Curiously, some of these RNA binding proteins have prion‐like domains, with a propensity to self‐aggregation. The emerging hypothesis that a focal cascade of toxic protein aggregates, and their consequent non–cell‐autonomous spread to neighborhood groups of neurons, fits the classical temporo‐spatial progression of ALS. This article reviews the current research efforts toward understanding the role of RNA‐processing regulation and protein aggregates in ALS. Muscle Nerve 47:330‐338, 2013     

Quantitative Detection of Thrombin Activity in an Ischemic Stroke Model

Thrombin, a central factor in thrombogenesis, affects cells in the brain through protease activated receptors. Low levels of thrombin activity are neuroprotective while higher levels are deleterious, and we have therefore developed a new method for its direct quantitative measurement in brain slices following stroke. Thrombin activity was measured by a fluorescent substrate on fresh coronal slices taken from the ipsilateral and contralateral hemispheres 24–72 h following permanent right middle cerebral artery occlusion. Prolyl endopeptidase and aminopeptidases were inhibited as a critical step to insure the specificity of the assay for thrombin detection. Infarct volume was assessed using TTC staining. Thrombin activity in the right ischemic hemisphere was significantly higher compared to the contralateral hemisphere (32?±?6 and 27?±?10 mU/ml, mean?±?SE in the two most affected slices from the ischemic hemisphere vs. 21?±?6 and 8?±?2 mU/ml in corresponding contralateral slices; p?<?0.05). Thrombin levels in the ischemic and contralateral hemispheres were significantly higher compared to healthy control mice and were above the range known to be protective to brain cells. A significant correlation was found between thrombin activity in the ischemic hemisphere and the infarct volume. Results of studies based on this method may translate into potential thrombin based therapies.     

The history of parkinsonism: Descriptions in ancient Indian medical literature

The clinical syndrome of parkinsonism was identified in ancient India even before the period of Christ and was treated methodically. The earliest reference to bradykinesia dates to 600 bc . Evidences prove that as early as 300 bc , Charaka proposed a coherent picture of parkinsonism by describing tremor, rigidity, bradykinesia, and gait disturbances as its components. The scenario was further developed by Madhava, Vagbhata, and Dalhana all through history. The 15th‐century classic “Bhasava rajyam” introduced the term kampavata, which may be regarded as an ayurvedic analogue of parkinsonism. The pathogenesis of kampavata centered on the concept of imbalance in the vata factor, which controls psychomotor activities. The essential element in therapy was the administration of powdered seed of Mucuna pruriens, or atmagupta, which as per reports, contains 4%?6% of levodopa. In addition to proving the existence and identification of parkinsonism in ancient India, the study points to the significance of ancient Indian Sanskrit works in medical history. © 2013 Movement Disorder Society