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1.  Clinical Profile of Long-Term Survivors and Nonsurvivors With Type 2 Diabetes 
Diabetes Care  2013;36(8):2190-2197.
To compare clinical profile of long-term survivors and nonsurvivors with type 2 diabetes (T2DM).
After conducting a retrospective survey of >200,000 case records, we identified T2DM survivors (>40 years of duration) and age at diagnosis and sex-matched T2DM nonsurvivors. Prevalence of complications and causes of death were analyzed. Retinopathy was diagnosed by retinal photography. Microalbuminuria and macroalbuminuria, peripheral vascular disease based on ankle-brachial index <0.9, coronary artery disease based on history of myocardial infarction or coronary revascularization, and neuropathy based on vibration perception threshold >20 V were compared in both groups.
The mean duration of diabetes of survivors (n = 238) was 43.7 ± 3.9 years, and that of the nonsurvivors (n = 307), at time of death, was 22.4 ± 11.0 years (P < 0.001). Nonsurvivors had significantly higher systolic and diastolic blood pressures, plasma glucose, HbA1c, serum cholesterol, LDL cholesterol, and triglycerides and lower HDL cholesterol compared with long-term survivors (P < 0.001 for all parameters except systolic blood pressure, which was P = 0.027). Myocardial infarction (46.4%) and renal failure (16.6%) were the most common causes of death. Prevalence of most complications was higher among survivors because of longer duration and older age, as follows, for survivors versus nonsurvivors: retinopathy, 76 vs. 62%; microalbuminuria, 39.1 vs. 27.3%; macroalbuminuria, 8.4 vs. 23.7%; neuropathy, 86.5 vs. 63.5%; peripheral vascular disease, 23.1 vs. 11.4%; and coronary artery disease, 44.5 vs. 40.7%.
Long-term survivors with T2DM had better glycemic and blood pressure control and more favorable lipid profiles.
PMCID: PMC3714469  PMID: 23564913
2.  Serum Adiponectin Helps to Differentiate Type 1 and Type 2 Diabetes Among Young Asian Indians 
This study assessed whether serum adiponectin could be used as a biochemical marker to differentiate type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM) among young Asian Indians.
Research Design and Methods
We recruited age- and sex-matched individuals with physician-diagnosed T1DM (n=70) and T2DM (n=72). All were 12–27 years of age with a duration of diabetes of >2 years, at a large tertiary-care diabetes center in Chennai, southern India. Age- and sex-matched individuals with normal glucose tolerance (NGT) (n=68) were selected from an ongoing population study. NGT was defined using World Health Organization criteria. Serum total adiponectin was measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curves were used to identify adiponectin cut points for discriminating T1DM from T2DM.
Adiponectin levels were higher in T1DM and lower in T2DM compared with the NGT group (9.89, 3.88, and 6.84 μg/mL, respectively; P<0.001). In standardized polytomous regression models, adiponectin was associated with T1DM (odds ratio [OR]=1.131 per SD; 95% confidence interval [CI], 1.025–1.249) and T2DM (OR=0.628 per SD; 95% CI, 0.504–0.721) controlled for age, gender, waist circumference, body mass index, hypertension, glycated hemoglobin, total cholesterol, serum triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, family history of T2DM, and estimated glomerular filtration rate. Using ROC analysis, an adiponectin cut point of 5.1 μg/mL had a C statistic of 0.886 (95% CI, 0.836–0.953), sensitivity of 80.6%, and specificity of 80.6% to differentiate T1DM from T2DM. Using the 5.1 μg/mL cut point, 80.6% of T1DM and 81.8% of T2DM would be correctly classified.
Serum adiponectin is a useful biochemical marker for differentiating T1DM and T2DM among young Asian Indians.
PMCID: PMC3746282  PMID: 23902401
3.  Protective Role of S-Nitrosoglutathione (GSNO) Against Cognitive Impairment in Rat Model of Chronic Cerebral Hypoperfusion 
Chronic cerebral hypoperfusion (CCH), featuring in most of the Alzheimer's disease spectrum, plays a detrimental role in brain amyloid-β (Aβ) homeostasis, cerebrovascular morbidity, and cognitive decline; therefore, early management of cerebrovascular pathology is considered to be important for intervention in the impending cognitive decline. S-nitrosoglutathione (GSNO) is an endogenous nitric oxide carrier modulating endothelial function, inflammation, and neurotransmission. Therefore, the effect of GSNO treatment on CCH-associated neurocognitive pathologies was determined in vivo by using rats with permanent bilateral common carotid artery occlusion (BCCAO), a rat model of chronic cerebral hypoperfusion. We observed that rats subjected to permanent BCCAO showed a significant decrease in learning/memory performance and increases in brain levels of Aβ and vascular inflammatory markers. GSNO treatment (50 μg/kg/day for 2 months) significantly improved learning and memory performance of BCCAO rats and reduced the Aβ levels and ICAM-1/VCAM-1 expression in the brain. Further, in in vitro cell culture studies, GSNO treatment also decreased the cytokine-induced proinflammatory responses, such as activations of NFκB and STAT3 and expression of ICAM-1 and VCAM-1 in endothelial cells. In addition, GSNO treatment increased the endothelial and microglial Aβ uptake. Additionally, GSNO treatment inhibited the β-secretase activity in primary rat neuron cell culture, thus reducing secretion of Aβ, suggesting GSNO mediated mechanisms in anti-inflammatory and anti-amyloidogenic activities. Taken together, these data document that systemic GSNO treatment is beneficial for improvement of cognitive decline under the conditions of chronic cerebral hypoperfusion and suggests a potential therapeutic use of GSNO for cerebral hypoperfusion associated mild cognitive impairment in Alzheimer's disease.
PMCID: PMC4040220  PMID: 23254638
Alzheimer's disease; amyloid-β; bilateral common carotid artery occlusion; cerebral hypoperfusion; inflammation; S-nitrosylation; S-nitrosoglutathione
4.  Simvastatin Ameliorates Cauda Equina Compression Injury in a Rat Model of Lumbar Spinal Stenosis 
Lumbar spinal stenosis (LSS) is the leading cause of morbidity and mortality worldwide. LSS pathology is associated with secondary injury caused by inflammation, oxidative damage and cell death. Apart from laminectomy, pharmacological therapy targeting secondary injury is limited. Statins are FDA-approved cholesterol-lowering drug. They also show pleiotropic anti-inflammatory, antioxidant and neuroprotective effects. To investigate the therapeutic efficacy of simvastatin in restoring normal locomotor function after cauda equina compression (CEC) in a rat model of LSS, CEC injury was induced in rats by implanting silicone gels into the epidural spaces of L4 and L6. Experimental group was treated with simvastatin (5 mg/kg body weight), while the injured (vehicle) and sham operated (sham) groups received vehicle solution. Locomotor function in terms of latency on rotarod was measured for 49 days and the threshold of pain was determined for 14 days. Rats were sacrificed on day 3 and 14 and the spinal cord and cauda equina fibers were extracted and studied by histology, immunofluorescence, electron microscopy (EM) and TUNEL assay. Simvastatin aided locomotor functional recovery and enhanced the threshold of pain after the CEC. Cellular Infiltration and demyelination decreased in the spinal cord from the simvastatin group. EM revealed enhanced myelination of cauda equina in the simvastatin group. TUNEL assay showed significantly decreased number of apoptotic neurons in spinal cord from the simvastatin group compared to the vehicle group. Simvastatin hastens the locomotor functional recovery and reduces pain after CEC. These outcomes are mediated through the neuroprotective and anti-inflammatory properties of simvastatin. The data indicate that simvastatin may be a promising drug candidate for LSS treatment in humans.
PMCID: PMC3587651  PMID: 23188522
Spinal stenosis; Simvastatin; Cauda equina; Demyelination; g-ratio
5.  Ameliorative Potential of Tamarindus indica on High Fat Diet Induced Nonalcoholic Fatty Liver Disease in Rats 
The Scientific World Journal  2014;2014:507197.
Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms.
PMCID: PMC3932208  PMID: 24688399
6.  Spinal Cord Injury Induced Arrest in Estrous Cycle of Rats Is Ameliorated by S-nitrosoglutathione: Novel Therapeutic Agent to Treat Amenorrhea 
The journal of sexual medicine  2011;9(1):10.1111/j.1743-6109.2011.02526.x.
Amenorrhea following spinal cord injury (SCI) has been well documented. There has been little research on the underlying molecular mechanisms and therapeutics.
The purpose of the present study was to investigate the effect of GSNO in ameliorating SCI-induced amenorrhea through affecting the expression of CX43, NFkB, and ERβ protein.
SCI was induced in female SD rats at the T9-T10 level. Estrous stage was determined by vaginal smear. GSNO (50 μg/kg body weight) was gavage fed daily. Animals were sacrificed on day 7 and 14 post SCI. Ovaries were fixed for histological and biochemical studies. Expression levels of ERβ, CX-43, and NFkB were analyzed by Western blot and immunofluorescence.
Main Outcome Measures
GSNO hastens resumption of the estrous cycle following SCI-induced transient arrest.
Resumption of estrous cycle was hastened by GSNO. Atretic and degenerating follicles seen in the ovary of SCI rats on day 14 post-SCI were decreased in GSNO treated animals. The increased CX43 expression observed with SCI ovary was decreased by GSNO. ERβ expression decreased significantly on day 7 and 14 post-SCI and was restored with GSNO treatment. Following SCI, NFkB expression was increased in the ovarian follicles and the expression was reduced with GSNO administration. The number of terminal deoxynucleotidyl transferase-mediated biotinylated uridine triphosphate (UTP) nick end labeling positive follicular and luteal cells was increased after SCI. GSNO-treated animals had significantly fewer apoptotic cells in the ovary.
SCI-induced amenorrhea is accompanied by an increase in CX43 expression and a decrease in ERβ expression. SCI animals treated with GSNO resumed the estrous cycle significantly earlier. These results indicate a potential therapeutic value for GSNO in treating amenorrhea among SCI patients.
PMCID: PMC3809072  PMID: 22024253
Spinal Cord Injury; Amenorrhea; Sexual Function; Estrous Cycle
7.  An Experimental Approach for Selecting Appropriate Rodent Diets for Research Studies on Metabolic Disorders 
BioMed Research International  2013;2013:752870.
Diverse high energy diets have been utilized to precipitate obesity and related metabolic disorders in rodent models, though the dietary intervention has not absolutely been standardized. The present study established usage of a customized semipurified normal control diet (NCD) and high fat diet (HFD), for research studies on diet-induced metabolic disorders in albino rats. Male Wistar rats were fed with normal pellet diet (NPD) or customized NCDs I, II, III or HFDs I, II, III for 12 weeks and parameters, namely, body weight, visceral adiposity, serum triglycerides, cholesterol, and glucose were evaluated to select an appropriate NCD and HFD. The selected HFD was further evaluated for induction of fatty liver, whilst type 2 diabetes (T2D) induction was confirmed in HFD and streptozotocin (STZ) induced diabetes model in Wistar rats. Amongst different diets tested, NCD-I and HFD-I were selected, since NCD-I exhibited close resemblance to NPD, whereas HFD-I induced metabolic alterations, particularly obesity and dyslipidemia consistently. Moreover, HFD-I elevated terminal hepatic lipids, while HFD-I/STZ treatment augmented insulin resistance index and serum glucose levels significantly indicating effective induction of fatty liver and T2D, respectively. Therefore, customized semipurified NCD-I and HFD-I can be recommended for research studies on diet-induced metabolic disorders in albino Wistar rats.
PMCID: PMC3787574  PMID: 24151620
8.  S-Nitrosoglutathione administration ameliorates cauda equina compression injury in rats 
Neuroscience and medicine  2012;3(3):294-305.
Lumbar spinal stenosis (LSS) causes ischemia, inflammation, demyelination and results in dysfunction of the cauda equina (CE), leading to pain and locomotor functional deficits. We investigated whether exogenous administration of S-nitrosoglutathione (GSNO), an endogenous redox modulating anti-neuroinflammatory agent, hastens functional recovery in a CE compression (CEC) rat model. CEC was induced in adult female rats by the surgical implantation of two silicone blocks within the epidural spaces of L4-L6 vertebrae. GSNO (50 μg/kg body weight) was administered by gavage 1 h after the injury, and the treatment was continued daily thereafter. GSNO induced change in the pain threshold was evaluated for four days after the compression. Tissue analyses and locomotor function evaluation were carried out at two weeks and four weeks after the CEC respectively. GSNO significantly improved motor function in CEC rats as evidenced by an increased latency on rotarod compared with vehicle-treated CEC rats. CEC induced hyperalgesia was decreased by GSNO. GSNO also increased the expression of VEGF, reduced cellular infiltration (H&E staining) and apoptotic cell death (TUNEL assay), and hampered demyelination (LFB staining and g-ratio). These data demonstrate that administration of GSNO after CEC decreased inflammation, hyperalgesia and cell death leading to improved locomotor function of CEC rats. The therapeutic potential of GSNO observed in the present study with CEC rats suggests that GSNO is a candidate drug to test in LSS patients.
PMCID: PMC3755380  PMID: 23997981
LSS; VEGF; demyelination; g-ratio; neuroprotection
9.  Predictive parameters for angiography and embolization in the bleeding pelvic fracture 
In the bleeding pelvic fracture, decision needs to be made on definitive control of bleeding whilst resuscitation. The decision for angiography in unstable patients is difficult and this study hopes to identify the parameters that may aid in this decision.
121 patients with traumatic pelvic fractures were identified from June 2005 till June 2010, from the National University Hospital, Singapore. Out of these 121 patients, 15 patients who underwent angiographic evaluation were identified. 11 out of the 15 had angiography and embolization done, while the remaining 4 only had angiography done. Another group of 29 patients who had not undergone angiography were identified from the main population via age-matched criteria. Clinical parameters were compared between the 15 angiography patients and the 29 non-angiography group of patients.
Angiography group had a larger proportion (80%) with contrast blush noted on contrast-enhanced CT scan (CECT), a higher proportion with unstable pelvic fracture patterns as classified by Tile (80%), and Young and Burgess (92.4%) (p < 0.05). Embolized group had higher proportion (81.8%) with hematoma and with blush on CECT (100%), and higher proportion with unstable fracture patterns (UFPs) (72.7%) as classified by Tile (p < 0.05). Positive predictive value for embolization using hematoma alone is 39% while that of blush alone is 73% and unstable Tile fracture alone is 47%. Positive predictive value of combined hematoma, blush and unstable Tile fracture pattern is 75%.
Significant predictive factors for angiogram would be unstable pelvic fracture patterns, presence of hematoma and contrast blushing on CT.
PMCID: PMC3880531
Pelvic fracture; Angiogram; Embolization
10.  Stimulation of functional recovery via the mechanisms of neurorepair by S-nitrosoglutathione and motor exercise in a rat model of transient cerebral ischemia and reperfusion 
Stroke disability stems from insufficient neurorepair mechanisms. Improvement of functions has been achieved through rehabilitation or therapeutic agents. Therefore, we combined exercise with a neurovascular protective agent, S-nitrosoglutathione (GSNO), to accelerate functional recovery.
Stroke was induced by middle cerebral artery occlusion for 60 min followed by reperfusion in adult male rats. Animals were treated with vehicle (IR group), GSNO (0.25 mg/kg, GSNO group), rotarod exercise (EX group) and GSNO plus exercise (GSNO+EX group). The groups were studied for 14 days to determine neurorepair mechanisms and functional recovery.
Treated groups showed reduced infarction, decreased neuronal cell death, enhanced neurotrophic factors, and improved neurobehavioral functions. However, the GSNO+EX showed greater functional recovery (p<0.05) than the GSNO or the EX group. A GSNO sub group, treated 24 hours after IR, still showed motor function recovery (p<0.001). The protective effect of GSNO or exercise was blocked by the inhibition of Akt activity.
GSNO and exercise aid functional recovery by stimulating neurorepair mechanisms. The improvements by GSNO and exercise depend mechanistically on the Akt pathway. A combination of exercise and GSNO shows greater functional recovery. Improved recovery with GSNO, even administered 24 hours post-IR, demonstrates its clinical relevance.
PMCID: PMC3471563  PMID: 22717646
GSNO; IR; motor exercise; neurorepair; neurobehavior; rehabilitation; S-nitrosylation; stroke
11.  Development and Validation of a UV Spectrophotometric Method for the Simultaneous Estimation of Eprosartan Mesylate and Hydrochlorothiazide in Bulk and Formulations 
A simple, efficient, precise and accurate absorbance ratio method have been developed for the estimation of eprosartan mesylate and hydrochlorothiazide in pure and in fixed dose combination. In this method, UV spectra of eprosartan mesylate and hydrochlorothiazide were overlayed which involves the formation of Q-absorbance equation at 249.1 nm (isobestic point) and 274.5 nm, the max of hydrochlorothiazide. Both the drugs obeyed Beers law in the concentration range of 6-36 μg/ml and 1-10 μg/ml for eprosartan mesylate and hydrochlorothiazide, respectively. The accuracy of the method was determined by recovery studies and was found to be in the range of 102.29-103.10% and 99.52-101.60% for eprosartan mesylate and hydrochlorothiazide, respectively. The method was validated as per ICH guidelines and statistically. The method showed good reproducibility and recovery with % RSD less than 2. The method was found to be simple, economic, accurate and reproducible and can be used for routine analysis of eprosartan mesylate and hydrochlorothiazide in pure and in fixed dose combinations.
PMCID: PMC3425070  PMID: 22923871
Absorbance ratio method; eprosartan mesylate; hydrochlorothiazide; ICH guidelines; method validation
12.  S-Nitrosoglutathione reduces oxidative injury and promotes mechanisms of neurorepair following traumatic brain injury in rats 
Traumatic brain injury (TBI) induces primary and secondary damage in both the endothelium and the brain parenchyma, collectively termed the neurovascular unit. While neurons die quickly by necrosis, a vicious cycle of secondary injury in endothelial cells exacerbates the initial injury in the neurovascular unit following TBI. In activated endothelial cells, excessive superoxide reacts with nitric oxide (NO) to form peroxynitrite. Peroxynitrite has been implicated in blood brain barrier (BBB) leakage, altered metabolic function, and neurobehavioral impairment. S-nitrosoglutathione (GSNO), a nitrosylation-based signaling molecule, was reported not only to reduce brain levels of peroxynitrite and oxidative metabolites but also to improve neurological function in TBI, stroke, and spinal cord injury. Therefore, we investigated whether GSNO promotes the neurorepair process by reducing the levels of peroxynitrite and the degree of oxidative injury.
TBI was induced by controlled cortical impact (CCI) in adult male rats. GSNO or 3-Morpholino-sydnonimine (SIN-1) (50 μg/kg body weight) was administered orally two hours following CCI. The same dose was repeated daily until endpoints. GSNO-treated (GSNO group) or SIN-1-treated (SIN-1 group) injured animals were compared with vehicle-treated injured animals (TBI group) and vehicle-treated sham-operated animals (Sham group) in terms of peroxynitrite, NO, glutathione (GSH), lipid peroxidation, blood brain barrier (BBB) leakage, edema, inflammation, tissue structure, axon/myelin integrity, and neurotrophic factors.
SIN-1 treatment of TBI increased whereas GSNO treatment decreased peroxynitrite, lipid peroxides/aldehydes, BBB leakage, inflammation and edema in a short-term treatment (4-48 hours). GSNO also reduced brain infarctions and enhanced the levels of NO and GSH. In a long-term treatment (14 days), GSNO protected axonal integrity, maintained myelin levels, promoted synaptic plasticity, and enhanced the expression of neurotrophic factors.
Our findings indicate the participation of peroxynitrite in the pathobiology of TBI. GSNO treatment of TBI not only reduces peroxynitrite but also protects the integrity of the neurovascular unit, indicating that GSNO blunts the deleterious effects of peroxynitrite. A long-term treatment of TBI with the same low dose of GSNO promotes synaptic plasticity and enhances the expression of neurotrophic factors. These results support that GSNO reduces the levels of oxidative metabolites, protects the neurovascular unit, and promotes neurorepair mechanisms in TBI.
PMCID: PMC3158546  PMID: 21733162
13.  A Single-Center, Open, Comparative Study of the Effect of Using Self-Monitoring of Blood Glucose to Guide Therapy on Preclinical Atherosclerotic Markers in Type 2 Diabetic Subjects 
The aim of our study was to determine the effect of treatment based on preprandial and postprandial self-monitoring of blood glucose (SMBG) on the progression of carotid intima-medial thickness (CIMT) in noninsulin-treated type 2 diabetes mellitus (T2DM) subjects.
In this 18-month prospective trial, we recruited subjects 18–70 years of age, treated with metformin and sulfonylurea, with a standardized hemoglobin A1c (HbA1c) level ≤9.0%. Subjects were randomized to use of fasting/preprandial (FP) SMBG results to adjust evening medication or use of postprandial (PP) SMBG results to adjust morning medication. The primary end point was change in CIMT; change in HbA1c was a secondary end point.
Of the 300 subjects randomized, 280 (140 in each group) completed all biochemical tests and CIMT analysis. Carotid intima-medial thickness was reduced significantly in PP subjects from 0.78 (±0.15) mm to 0.73 (±0.14) mm (p < 0.005), but no significant CIMT reduction was seen in FP subjects. A significant reduction in HbA1c was also seen in the PP group (p < 0.005) but not in the FP group 1 (p = 0.165). Significant improvements in body mass index (p = 0.038), waist circumference (p < 0.001), systolic blood pressure (p = 0.008), and serum cholesterol (p = 0.02) were also seen in PP subjects but not in FP subjects.
Use of postprandial SMBG data to adjust therapy was associated with a significant regression of carotid intima-medial thickening and a reduction in HbA1c in T2DM, whereas no significant improvement in these parameters was seen in subjects who used fasting/preprandial SMBG data for therapy adjustment.
PMCID: PMC2909528  PMID: 20663460
carotid intima-medial thickness; diabetes; postprandial; preprandial; self-monitoring
14.  Phage Displayed Short Peptides against Cells of Candida albicans Demonstrate Presence of Species, Morphology and Region Specific Carbohydrate Epitopes 
PLoS ONE  2011;6(2):e16868.
Candida albicans is a commensal opportunistic pathogen, which can cause superficial infections as well as systemic infections in immuocompromised hosts. Among nosocomial fungal infections, infections by C. albicans are associated with highest mortality rates even though incidence of infections by other related species is on the rise world over. Since C. albicans and other Candida species differ in their susceptibility to antifungal drug treatment, it is crucial to accurately identify the species for effective drug treatment. Most diagnostic tests that differentiate between C. albicans and other Candida species are time consuming, as they necessarily involve laboratory culturing. Others, which employ highly sensitive PCR based technologies often, yield false positives which is equally dangerous since that leads to unnecessary antifungal treatment. This is the first report of phage display technology based identification of short peptide sequences that can distinguish C. albicans from other closely related species. The peptides also show high degree of specificity towards its different morphological forms. Using fluorescence microscopy, we show that the peptides bind on the surface of these cells and obtained clones that could even specifically bind to only specific regions of cells indicating restricted distribution of the epitopes. What was peculiar and interesting was that the epitopes were carbohydrate in nature. This gives insight into the complexity of the carbohydrate composition of fungal cell walls. In an ELISA format these peptides allow specific detection of relatively small numbers of C. albicans cells. Hence, if used in combination, such a test could help accurate diagnosis and allow physicians to initiate appropriate drug therapy on time.
PMCID: PMC3043061  PMID: 21364990
15.  Simvastatin protects bladder and renal functions following spinal cord injury in rats 
Urinary bladder and renal dysfunction are secondary events associated with spinal cord injury (SCI) in humans. These secondary events not only compromise quality of life but also delay overall recovery from SCI pathophysiology. Furthermore, in experimental models the effects of SCI therapy on bladder and renal functions are generally not evaluated. In this study, we tested whether simvastatin improves bladder and renal functions in a rat model of experimental SCI.
SCI was induced by controlled contusion of T9-T10 in adult female rats. Simvastatin (5 mg/Kg body weight) was administered at two hours after SCI and repeated every 24 hours until the end point. Simvastatin-treated SCI animals (simvastatin group) were compared with vehicle-treated SCI animals (vehicle group) in terms of the Basso Beattie Bresnahan score, tissue morphology, cell death, and bladder/renal functions.
The urinary bladder of vehicle animals showed a 4.3-fold increase in size and a 9-fold increase in wet weight compared to sham animals. Following SCI, the urine to plasma osmolality ratio increased initially but decreased 1 week after SCI. Hematoxylin and eosin staining of bladder tissue showed transitional epithelial hyperplasia, degeneration of lamina propria, and enlargement of tunica adventia in addition to detrusor muscle hypertrophy. Rats treated with simvastatin for 14 days displayed remarkable recovery by showing decreased bladder size and maintenance of a normal urine/plasma osmolality ratio, in addition to improved locomotion. The muscularis layer of the bladder also regained its compact nature in simvastatin animals. Moreover, SCI-induced renal caspase-3 activity was significantly decreased in the simvastatin group indicating the ability of simvastatin to reduce the renal tubular apoptosis.
Post-injury administration of simvastatin ameliorates bladder and renal dysfunction associated with SCI in rats.
PMCID: PMC2873501  PMID: 20403180
16.  Administration of S-nitrosoglutathione after traumatic brain injury protects the neurovascular unit and reduces secondary injury in a rat model of controlled cortical impact 
Traumatic brain injury (TBI) is a major cause of preventable death and serious morbidity in young adults. This complex pathological condition is characterized by significant blood brain barrier (BBB) leakage that stems from cerebral ischemia, inflammation, and redox imbalances in the traumatic penumbra of the injured brain. Once trauma has occurred, combating these exacerbations is the keystone of an effective TBI therapy. Following other brain injuries, nitric oxide modulators such as S-nitrosoglutathione (GSNO) maintain not only redox balance but also inhibit the mechanisms of secondary injury. Therefore, we tested whether GSNO shows efficacy in a rat model of experimental TBI.
TBI was induced by controlled cortical impact (CCI) in adult male rats. GSNO (50 μg/kg body weight) was administered at two hours after CCI. GSNO-treated injured animals (CCI+GSNO group) were compared with vehicle-treated injured animals (CCI+VEH group) in terms of tissue morphology, BBB leakage, edema, inflammation, cell death, and neurological deficit.
Treatment of the TBI animals with GSNO reduced BBB disruption as evidenced by decreased Evan's blue extravasation across brain, infiltration/activation of macrophages (ED1 positive cells), and reduced expression of ICAM-1 and MMP-9. The GSNO treatment also restored CCI-mediated reduced expression of BBB integrity proteins ZO-1 and occludin. GSNO-mediated improvements in tissue histology shown by reduction of lesion size and decreased loss of both myelin (measured by LFB staining) and neurons (assayed by TUNEL) further support the efficacy of GSNO therapy. GSNO-mediated reduced expression of iNOS in macrophages as well as decreased neuronal cell death may be responsible for the histological improvement and reduced exacerbations. In addition to these biochemical and histological improvements, GSNO-treated injured animals recovered neurobehavioral functions as evaluated by the rotarod task and neurological score measurements.
GSNO is a promising candidate to be evaluated in humans after brain trauma because it not only protects the traumatic penumbra from secondary injury and improves overall tissue structure but also maintains the integrity of BBB and reduces neurologic deficits following CCI in a rat model of experimental TBI.
PMCID: PMC2777134  PMID: 19889224
Ancient Science of Life  1989;8(3-4):293-297.
SURADARU LEPA CHURNA’-A Compound drug formulation in Ayurvedic system of medicine was analysed. The proximate chemical analysis, the microscopic method of identifying their ingredients, flourescese study and thin layer chromatographic studies of the drug have been reported in this paper.
PMCID: PMC3336721  PMID: 22557664
Ancient Science of Life  1986;5(4):263-268.
Dried floral buds of Mesua ferrea Linn, dried fruits of Dillenia pentagyna Roxb and dried fruiting inflorescence of Cinnamomum wightii Meissn are used as Nagakesara in different regions of India. This elaborate study presents to the pharmacognosy of these three different drugs of Nagakesara.
PMCID: PMC3331473  PMID: 22557537
19.  STANDARDISATION OF “HAB – E – BUKHAR” (Unani Medicine) 
Ancient Science of Life  1985;5(1):37-39.
‘HAB-E-BUKHAR’ – a compound drug formulation in Unani System of medicine has been analysed. The microscopic method of identification of few of its ingredients (Sath-e-gulu, Thabasheer); Quantitative analysis of Quinine sulphate, other physio-chemical contents and the T.L.C. of the drug have also been reported here.
PMCID: PMC3331439  PMID: 22557497
Ancient Science of Life  1984;4(2):106-109.
The gum Kidamali is an important oleoresin drug in the Indian System of Medicine. The market sample of Madras Crude drug trade has been identified as the gums of Gardenia gummifera Linn. f. of Rubiaceae. The morphology, microscopical structure of the source material, the fluorescence analysis and the chemical studies including thin layer chromatography of the drug are reported.
PMCID: PMC3331502  PMID: 22557460
Ancient Science of Life  1984;3(4):203-206.
Kutaja bija, Kudasappalai or Inderjou is an important seed drug in Ayurveda, Siddha and Unani Medicines. The market sample of Madras Crude drug trade has been identified in our laboratory as the seeds of Holarrhena – anti – dysenterica wall of the family Apocynaceae. The morphology, anatomy, fluorescence analysis and chemical studies of the drugs are reported.
PMCID: PMC3331573  PMID: 22557406
Ancient Science of Life  1984;3(3):140-142.
Kattusirakam or Vanajira is an important fruit drug in Siddha and Ayurveda systems of Medicine. The market sample of Madras has been identified in our laboratory as the fruits, commonly known as seeds of Centratherum anthelminticum (Willd) Kuntz. (Syn. Veronia anthelmintica Willd) of the family Compositate. The morphology, anatomy, fluorescence analysis and chemical characters of the drug are dealt with here.
PMCID: PMC3331554  PMID: 22557396
Ancient Science of Life  1983;3(2):67-71.
Nilavarai Curnam, a compound drug formulation in Siddha System of Medicine was analysed. The Microscopic methods of identifying their ingredients, Chemical analysis, Fluorescence, and Thin Layer Chromatographic studies of the drug have been reported here.
PMCID: PMC3331551  PMID: 22557382
Ancient Science of Life  1983;3(1):27-30.
Miskitaramashia is a special single drug in Unani system of medicine and it has been identified as Lallemantia royleana (Wall) Benth. Of the family Labiacae. Its pharmacognostical characters hava also been reported here.
PMCID: PMC3331537  PMID: 22557373
Ancient Science of Life  1982;1(4):200-205.
The pharmacognosy of Nattu Attivdayam the corms of Cryptocoryne spiralis Fisch – its macroscopical, microscopical and chemical studies – is reported
PMCID: PMC3336695  PMID: 22556490

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