In rats, ageing results in dysfunctional patterns of micturition and diminished sexual reflexes that may reflect degenerative changes within spinal circuitry. In both sexes the dorsal lateral nucleus and the spinal nucleus of the bulbospongiosus, which lie in the L5-S1 spinal segments, contain motor neurons that innervate perineal muscles, and the external anal and urethral sphincters. Neurons in the sacral parasympathetic nucleus of these segments provide autonomic control of the bladder, cervix and penis and other lower urinary tract structures. Interneurons in the dorsal gray commissure and dorsal horn have also been implicated in lower urinary tract function. This study investigates the cellular localisation of PG-21 androgen receptors, steroid receptor co-activator one (SRC-1) and the phosphorylated form of c-AMP response element binding protein (pCREB) within these spinal nuclei. These are components of signalling pathways that mediate cellular responses to steroid hormones and neurotrophins. Nuclear expression of PG-21 androgen receptors, SRC-1 and pCREB in young and aged rats was quantified using immunohistochemistry. There was a reduction in the number of spinal neurons expressing these molecules in the aged males while in aged females, SRC-1 and pCREB expression was largely unchanged. This suggests that the observed age-related changes may be linked to declining testosterone levels. Acute testosterone therapy restored expression of PG-21 androgen receptor in aged and orchidectomised male rats, however levels of re-expression varied within different nuclei suggesting a more prolonged period of hormone replacement may be required for full restoration.
Aged ; Androgens ; Animals ; Carrier Proteins ; Cervix Uteri ; Female ; Hormone Replacement Therapy ; Horns ; Humans ; Immunohistochemistry ; Interneurons ; Male ; Motor Neurons ; Muscles ; Nerve Growth Factors ; Neurons ; Penis ; Rats ; Receptors, Androgen ; Receptors, Steroid ; Reflex ; Response Elements ; Spinal Cord ; Testosterone ; Urethra ; Urinary Bladder ; Urinary Tract ; Urination ; Young Adult

BACKGROUND: Emergencies such as road traffic accidents (RTAs), acute myocardial infarction (AMI) and cerebrovascular accident (CVA) are the most common causes of death and disability in India. Robust emergency medicine (EM) services and proper education on acute care are necessary. In order to inform curriculum design for training programs, and to improve the quality of EM care in India, a better understanding of patient epidemiology and case burden presenting to the emergency department (ED) is needed.METHODS: This study is a retrospective chart review of cases presenting to the ED at Kerala Institute of Medical Sciences (KIMS), a private hospital in Trivandrum, Kerala, India, from November 1, 2011 to April 21, 2012 and from July 1, 2013 to December 21, 2013. De-identified charts were systematically sampled and reviewed.RESULTS: A total of 1196 ED patient charts were analyzed. Of these patients, 55.35％ (n=662) were male and 44.7％ (n=534) were female. The majority (67.14％,n=803) were adults, while only 3.85％ (n=46) were infants. The most common chief complaints were fever (21.5％, n=257), renal colic (7.3％,n=87), and dyspnea (6.9％,n=82). The most common ED diagnoses were gastrointestinal (15.5％,n=185), pulmonary (12.3％,n=147), tropical (11.1％,n=133), infectious disease and sepsis (9.9％,n=118), and trauma (8.4％,n=101).CONCLUSION: The patient demographics, diagnoses, and distribution of resources identifi ed by this study can help guide and shape Indian EM training programs and faculty development to more accurately refl ect the burden of acute disease in India.

Increased generation of reactive oxygen species (ROS) in vascular diseases such as atherosclerosis, diabetes, chronic renal failure and preeclampsia readily leads to impaired endothelium-dependent relaxation and vascular injury. To counteract ROS- and electrophile-mediated injury, cells can induce a number of genes encoding phase II detoxifying enzymes and antioxidant proteins. A cis-acting transcriptional regulatory element, designated as antioxidant response element (ARE) or electrophile response element (EpRE), mediates the transcriptional activation of genes such as heme oxygenase-1, gamma-glutamylcysteine synthethase, thioredoxin reductase, glutathione-S-transferase and NAD(P)H:quinone oxidoreductase. Other antioxidant enzymes such as superoxide dismutase and catalase and non-enzymatic scavengers such as glutathione are also involved in scavenging ROS. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a member of the Cap nno Collar family of basic region-leucine zipper (bZIP) transcription factors, plays an important role in ARE-mediated antioxidant gene expression. Kelch-like ECH-associated protein-1 (Keap1) normally sequesters Nrf2 in the cytoplasm in association with the actin cytoskeleton, but upon oxidation of cysteine residues Nrf2 dissociates from Keap1, translocates to the nucleus and binds to ARE sequences leading to transcriptional activation of antioxidant and phase II detoxifying genes. Protein kinase C (PKC), mitogen-activated protein kinases (MAPKs) and phosphotidylinositol 3-kinase (PI3K) have been implicated in the regulation of Nrf2/ARE signaling. We here review the evidence that the Nrf2/ARE signaling pathway plays an important role in vascular homeostasis and the defense of endothelial and smooth muscle cells against sustained oxidative stress associated with diseases such as atherosclerosis and preeclampsia.
Animals ; Antioxidants ; metabolism ; Atherosclerosis ; physiopathology ; Endothelial Cells ; metabolism ; Female ; Gene Expression Regulation ; Humans ; Muscle, Smooth, Vascular ; metabolism ; NF-E2-Related Factor 2 ; genetics ; physiology ; Oxidative Stress ; genetics ; physiology ; Pre-Eclampsia ; physiopathology ; Pregnancy ; Response Elements ; physiology ; Signal Transduction ; physiology