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1.  Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options 
Current Neuropharmacology  2009;7(1):65-74.
Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants, overproduction or incorporation of free radicals from environment to living system leads to serious penalty leading to neuro-degeneration. Neural cells suffer functional or sensory loss in neurodegenerative diseases. Apart from several other environmental or genetic factors, oxidative stress (OS) leading to free radical attack on neural cells contributes calamitous role to neuro-degeneration. Though, oxygen is imperative for life, imbalanced metabolism and excess reactive oxygen species (ROS) generation end into a range of disorders such as Alzheimer’s disease, Parkinson’s disease, aging and many other neural disorders. Toxicity of free radicals contributes to proteins and DNA injury, inflammation, tissue damage and subsequent cellular apoptosis. Antioxidants are now being looked upon as persuasive therapeutic against solemn neuronal loss, as they have capability to combat by neutralizing free radicals. Diet is major source of antioxidants, as well as medicinal herbs are catching attention to be commercial source of antioxidants at present. Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging. Antioxidants have a wide scope to sequester metal ions involved in neuronal plaque formation to prevent oxidative stress. In addition, antioxidant therapy is vital in scavenging free radicals and ROS preventing neuronal degeneration in post-oxidative stress scenario.
doi:10.2174/157015909787602823
PMCID: PMC2724665  PMID: 19721819
ROS; oxidative stress; antioxidants; neurodegenerative diseases; rns; amyloid; catalase; phagocytes.
2.  Falls and major orthopaedic surgery with peripheral nerve blockade: a systematic review and meta-analysis 
BJA: British Journal of Anaesthesia  2013;110(4):518-528.
Summary
The objective of this systematic review with meta-analysis was to determine the risk for falls after major orthopaedic surgery with peripheral nerve blockade. Electronic databases from inception through January 2012 were searched. Eligible studies evaluated falls after peripheral nerve blockade in adult patients undergoing major lower extremity orthopaedic surgery. Independent reviewers working in duplicate extracted study characteristics, validity, and outcomes data. The Peto odds ratio (OR) with 95% confidence intervals (CIs) were estimated from each study that compared continuous lumbar plexus blockade with non-continuous blockade or no blockade using a fixed effects model. Ten studies (4014 patients) evaluated the number of falls as an outcome. Five studies did not contain comparison groups. The meta-analysis of five studies [four randomized controlled trials (RCTs) and one cohort] compared continuous lumbar plexus blockade (631 patients) with non-continuous blockade or no blockade (964 patients). Fourteen falls occurred in the continuous lumbar plexus block group when compared with five falls within the non-continuous block or no block group (attributable risk 1.7%; number needed to harm 59). Continuous lumbar plexus blockade was associated with a statistically significant increase in the risk for falls [Peto OR 3.85; 95% CI (1.52, 9.72); P=0.005; I2=0%]. Evidence was low (cohort) to high (RCTs) quality. Continuous lumbar plexus blockade in adult patients undergoing major lower extremity orthopaedic surgery increases the risk for postoperative falls compared with non-continuous blockade or no blockade. However, attributable risk was not outside the expected probability of postoperative falls after orthopaedic surgery.
doi:10.1093/bja/aet013
PMCID: PMC3600943  PMID: 23440367
accidental falls; anaesthesia, conduction; arthroplasty, replacement, hip; arthroplasty, replacement, knee; muscle weakness; nerve block
3.  Genetic polymorphism in Plasmodium falciparum: Differentiation of parasite isolates of high & low virulence by RAPD 
Background & objectives:
The increase in Plasmodium falciparum infections which are associated with severe and complicated malaria and drug resistance has made control of malaria a difficult task. Extensive genetic polymorphism in P. falciparum has been reported from several parts of the world which affects the efficacy of sub-unit vaccines. The knowledge of genotypes of the parasite in a geographical region is therefore, important for effective management and control. The aim of the present study was to investigate the usefulness of random amplified polymorphic DNA (RAPD)-PCR technique for differentiation of P. falciparum isolates from patients presenting with severe (cerebral malaria) and mild malaria.
Methods:
Genetic polymorphism in 21 P. falciparum isolates obtained from patients found positive for P. falciparum by light microscopy was studied by RAPD-PCR analysis. Eleven RAPD primers were used for analysis of 21 P. falciparum isolates obtained from cerebral and non-cerebral malaria patients.
Results:
Of the 11 primers, only three (E-4, E-8, and R-8) produced useful polymorphic patterns. The cluster analysis based on UPGMA demonstrated that isolates causing cerebral malaria cluster separately from those causing uncomplicated malaria. However, the analysis of phylogenic tree showed that P. falciparum isolates causing non-cerebral and cerebral malaria clustered separately but showed relatedness.
Interpretation & conclusions:
The results of the present study showed that the RAPD-PCR was able to differentiate the isolates causing severe and mild malaria. The cluster analysis of the phylogenic tree suggested that the virulent strains evolved from less virulent strains as it clustered separately. RAPD technique may be useful in discriminating between the different isolates of the same species resulting in different clinical profiles.
PMCID: PMC3461743  PMID: 22960898
Cerebral malaria; genetic polymorphism; Plasmodium falciparum; RAPD; virulence
4.  Anaemia & expression levels of CD35, CD55 & CD59 on red blood cells in Plasmodium falciparum malaria patients from India 
Background & objectives:
Severe anaemia in Plasmodium falciparum (Pf) associated malaria is a leading cause of death despite low levels of parasitaemia. In an effort to understand the pathogenesis of anaemia we studied expression level of RBC complement regulatory proteins, CR1 (CD35), CD55 and CD59 with haemoglobin status in a group of malaria cases from Assam, Goa and Chennai, and in healthy controls.
Methods:
Flowcytometry was used to study expression of CR1, CD55 and CD59 in 50 Pf cases and 30 normal healthy volunteers. Giemsa stained thick and thin blood films were used for microscopic detection and identification of malarial parasites and parasite count.
Results:
No correlation was found between degree of expression of RBC surface receptors CR1, CD55 and CD59 with haemoglobin level. However, expression of CD55 was less in malaria cases than in healthy controls.
Interpretation & conclusions:
The present findings indicate that malaria infection changes the expression profile of complement regulatory protein CD55 irrespective of severity status of anaemia. Further studies are needed to explore the pathophysiology of anaemia in malaria cases in Assam where expression of RBC complement receptors appears to be low even in normal healthy population.
PMCID: PMC3135996  PMID: 21727667
Anaemia; Assam; CD55; CD59; CR1; Chennai; flowcytometry; Goa; India; Plasmodium falciparum
5.  Revisiting Metformin: Annual Vitamin B12 Supplementation may become Mandatory with Long-Term Metformin Use 
Monitoring of adverse drug reactions of a drug is a continuous process and runs through-out the life of a drug. Many rare adverse effects of a drug are documented after years of use; when a single case (signal generation) is reported leading subsequently to reporting of more cases. Deficiency of Vitamin B12 (vit B12) is a known sequel of prolonged metformin therapy. It was recommended to have annual measurement of serum vit B12 levels in patients on long term metformin therapy way back in 1970 itself. After more than 50 years of use of metformin, we have come to know that metformin induced vit B12 deficiency can cause neuropathy; forcing to change the recommendation from annual screening of vit B12 levels to annual supplementation of vit B12.
doi:10.4103/0975-1483.71621
PMCID: PMC3019388  PMID: 21264109
Metformin; neuropathy; type 2 diabetes
6.  Assessment of Awareness among Clinicians about Concepts in Undergraduate Pharmacology Curriculum: A Novel Cross-sectional Study 
Objective:
In the last 30 years, concepts in pharmacology have moved from Essential Medicines (EM) to P-drugs via the Rational Use of Medicines (RUM), but no structured study has evaluated the level of understanding among working clinicians about these concepts. The present study is designed to fulfill that lacuna.
Materials and Methods:
A cross-sectional study was carried out in and around the teaching hospitals attached to Medical Colleges, enrolling 504 clinicians from six centers across North India to fill-up a questionnaire containing 25 questions. The results were compiled using percentages and averages.
Results:
Only one-fourth of the participants claimed that they always prescribed Essential Medicines; no one could accurately count the number of drugs / drug combinations in the Indian Essential Drug list; only 15.1% of the clinicians used to write the generic names of drugs on a prescription slip; about one-third of the clinicians were not fully aware about the adverse effects, drug interactions, and contraindications of the drugs they prescribed; about 83% of the physicians admitted to rely on information from Medical Representatives (MRs) and the interest in research activities seemed to be lost.
Conclusion:
Results show a sorry state of affairs among clinicians, as far as the level of understanding about EM, P-drugs, and RUM is concerned, and points toward arranging more continuing medical education (CME) for clinicians regarding these concepts.
doi:10.4103/0975-1483.66797
PMCID: PMC2964763  PMID: 21042490
Clinicians; essential medicines; P-drugs; rational use of medicines
7.  FABRICATION AND CHARACTERIZATION OF A CARBON NANOTUBE-BASED NANOKNIFE 
Nanotechnology  2009;20(9):095701.
We demonstrate construction and testing of a prototype microtome knife for cutting ~100 nm thick slices of frozen-hydrated biological samples based on a multiwalled carbon nanotube (MWCNT). A piezoelectric-based 3-D manipulator was used inside a scanning electron microscope (SEM) to select and position individual MWCNTs, which were subsequently welded in place using electron beam-induced deposition (EBID). The knife is built on a pair of tungsten needles with provision to adjust the distance between the needle tips, accommodating various lengths of MWCNTs. We performed experiments to test the mechanical strength of MWCNT in the completed device using an atomic force microscope (AFM) tip. An increasing force was applied at the midpoint of nanotube until failure, which was observed in situ in the SEM. The maximum breaking force was approximately (8 × 10−7) N which corresponds well with the typical microtome cutting forces reported in the literature. In situ cutting experiments were performed on a cell biological embedding plastic (epoxy) by pushing it against the nanotube. Initial experiments show indentation marks on the epoxy surface. Quantitative analysis is currently limited by the surface asperities which have the same dimensions as the nanotube.
doi:10.1088/0957-4484/20/9/095701
PMCID: PMC2879632  PMID: 19417497
9.  Comparison and Suitability of Gel Matrix for Entrapping Higher Content of Enzymes for Commercial Applications 
To check the suitability of enzyme entrapped beads for use in pharmaceutical industry, amylase enzyme was entrapped in agar/agarose, polyacrylamide gels and calcium alginate beads. Sodium alginate of 1% concentration was found to be best with respect to immobilization efficiency and calcium alginate beads so obtained were not much susceptible to breakage. When sodium alginate- amylase mixture was added from a height of about 20-30 cm. into CaCl2 solution, size of beads was large at higher alginate concentration due to the increase in the size of droplet formation before entering into CaCl2 solution. Enzyme entrapped polyacrylamide and agar/agarose gels were fragile and could not withstand repeated use whereas enzyme entrapped in large calcium alginate beads was used successfully for 50 cycles for the conversion of starch into product without much damage to the beads under stirring conditions. Amylase preparation was also mixed with urease, lysozyme and coimmobilized in large sized calcium alginate beads. These beads were used for 10 repeated cycles to check the conversion of substrates into their products by their respective enzymes and we concluded that an enzyme or mixture of two or three enzymes can be immobilized in the same large sized calcium alginate beads. This will save the additional cost of bioreactor, manpower, maintenance conditions required for the conversion of one drug into another using enzyme/s entrapped in large sized beads.
doi:10.4103/0250-474X.65010
PMCID: PMC2929782  PMID: 20838527
Agar/agarose gel; calcium alginate; entrapment; enzyme; immobilization; polyacrylamide
12.  Strain-dependent twist–stretch elasticity in chiral filaments 
Coupling between axial and torsional degrees of freedom often modifies the conformation and expression of natural and synthetic filamentous aggregates. Recent studies on chiral single-walled carbon nanotubes and B-DNA reveal a reversal in the sign of the twist–stretch coupling at large strains. The similarity in the response in these two distinct supramolecular assemblies and at high strains suggests a fundamental, chirality-dependent nonlinear elastic behaviour. Here we seek the link between the microscopic origin of the nonlinearities and the effective twist–stretch coupling using energy-based theoretical frameworks and model simulations. Our analysis reveals a sensitive interplay between the deformation energetics and the sign of the coupling, highlighting robust design principles that determine both the sign and extent of these couplings. These design principles have already been exploited by nature to dynamically engineer such couplings, and have broad implications in mechanically coupled actuation, propulsion and transport in biology and technology.
doi:10.1098/rsif.2007.1145
PMCID: PMC2607403  PMID: 17895221
chirality; supramolecular assemblies; mechanical coupling; elastic rod theory; carbon nanotubes; DNA mechanics
13.  PATTERN PERFORMANCE OF SCHIZOPHRENIC PATIENTS ON LURIA-NEBRASKA NEURO-PSYCHOLOGICAL BATTERY 
Indian Journal of Psychiatry  2002;44(1):47-52.
Luria-Nebraska Neuro-psychological Battery, is now an established tool to assess brain damage in recent years. This test battery has been reported to be very useful to find out functional organization of the brain. The biological basis of psychiatry is also now well explained. The present study is directed towards the neuro-psychological functioning of schizophrenic disorder, and the findings are discussed in the light of biological researches. The pattern of performance of schizophrenia on Luria-Nebraska Neuro-psychological battery is indicating the possibility of combined cerebral dysfunction, more towards left hemisphere functions. No single localization was found responsible for this illness. Limitations of present study, and need for well organized further research is indicated using advance technology of brain imaging techniques and neuro-psychological profile of brain functioning, would be helpful for the rehabilitation purposes and to understand the illness better.
PMCID: PMC2953654  PMID: 21206881
Neuro-psychology; schizophrenia; Luria-Nebraska Battery
14.  NEURO-PSYCHOLOGICAL PROFILE OF EPILEPSY ON LURIA-NEBRASKA NEUROPSYCHOLOGICAL BATTERY 
Indian Journal of Psychiatry  2002;44(1):53-56.
Neuropsychological functioning of epileptic patients is emerging as an interesting area of research among clinician. There is sufficient evidence suggesting cognitive deficits among epileptics. No specific rehabilitation planning was prepared in this regard. The planning for rehabilitation can be prepared if a comprehensive functional organization of the brain of epileptics can be identified. The present study is directed towards the neuropsychological functioning of patients with idiopathic generalized epilepsies, and its comparison with normal controls. All the 60 subjects (30 normal controls and 30 epileptics), after matching their age and education were assessed on Luria-Nebraska Neuropsychological Battery (LNNB). The performance level and pattern of epileptics were significantly different than normal controls on all the parameters of LNNB. The battery could detect specific organic malfunctioning in epileptic patients.
PMCID: PMC2953655  PMID: 21206882
LNNB; Neuropsychology Epilepsy
15.  TEMPERAMENTAL CHARACTERISTICS AND PSYCHOPATHOLOGY AMONG CHILDREN OF ALCOHOLICS 
Indian Journal of Psychiatry  1997;39(3):226-231.
The impact of family and child rearing practices on personality development and psychiatric illnesses are well established. The present investigation is directed towards the study of psychopathology and temperamental characteristics of children of alcoholic parents, to find out correlation between these two areas and the role of alcoholism in child rearing practices. A group of 100 children of alcoholic parents was selected through random sampling between the age range of 4-12 years and compared with the children of nonalcoholic parents (N-100). Both groups were assessed on Temperamental Measurement Schedule. The student ‘t’ test and product moment was computed for comparative and correlation purposes. The children of alcoholics were found to be manifesting marked psychopathological disturbances. These children were also found to be more arrhythmic manifesting negative mood and low persistence as compared to the children of control group. The positive correlation between psychopathological and temperamental characteristics have been indicated.
PMCID: PMC2967119  PMID: 21584079
Children; alcoholism; personality; temperament; psychopathology
16.  High incidence of oesophageal and gastric cancer in Kashmir in a population with special personal and dietary habits. 
Gut  1992;33(1):11-15.
Over a three year period (1 July 1986 to 30 June 1989) all newly diagnosed and histologically proved cases of oesophageal and gastric cancer were recorded prospectively. Some 1515 cases of oesophageal cancer (1050 men and 465 women) and 966 cases of gastric cancer (789 men and 177 women) were registered. Seven patients had simultaneous oesophageal and gastric cancer. Age standardised incidence rates for oesophageal cancer were: men 43.6/100,000 per year; women 27.9/100,000 per year. The rates for gastric cancer were: men 36.7/100,000 per year, women 9.9/100,000 per annum. These figures were three to six times higher than those recorded by cancer registries in Banglore, Madras, and Bombay. The incidence rates for oesophageal and gastric cancer in Islamabad (southern district of Kashmir) were 4.1 to 5.4 times higher in men and 1.5 to 2.0 times higher in women than those for Kupwara (northern district of Kashmir). The incidence rates for oesophageal and gastric cancer in Muslims, Hindus, and Sikhs were different. The epidemiology of oesophageal cancer in Kashmir was similar to that found in the 'Asian oesophageal cancer belt'. At the same time Kashmir also had an unprecedented high incidence of gastric cancer. Kashmiries have special personal and dietary habits. Further studies are needed to define the relation between these habits and the occurrence of oesophageal and gastric cancer.
PMCID: PMC1373857  PMID: 1740265
17.  Endoscopic fine needle aspiration cytology in the diagnosis of gastro-oesophageal and colorectal malignancies. 
Gut  1991;32(7):745-748.
In a prospective study we compared the diagnostic accuracy of endoscopic fine needle aspiration cytology with that of brush cytology and forceps biopsy in relation to gross tumour pattern and site in 265 confirmed consecutive cases of malignancy of the oesophagus, stomach, colon, and rectum. Aspiration cytology gave the highest diagnostic accuracy (94%), which was significantly better than that of brush cytology (84.9%) and biopsy (87.2%) (p less than 0.005). The difference was mainly related to tumour pattern. When compared to brush cytology and biopsy aspiration cytology was significantly better in submucosal tumours (92.9% v 7.1% and 14.3%, p less than 0.001); in infiltrative malignancies (95.8% v 90.1% and 78.9%, p less than 0.01), and in ulceronecrotic malignancies (90.9% v 36.4% and 45.4%, p less than 0.05). In polypoid malignancies there was a significant trend (p less than 0.05) in favour of forceps biopsy, with a diagnostic yield of 100% compared with 95% for aspiration cytology and 93.3% for brush cytology. The accuracy of the different techniques was not significantly related to the site of the tumour. The cumulative accuracy of aspiration cytology and biopsy was significantly better than that of biopsy and brush cytology (98.5% v 90.9%, p less than 0.005). Aspiration cytology was diagnostic in 21 of 24 lesions that were negative with both brush cytology and biopsy. There were no false positive cytology or histology results. We conclude that aspiration cytology is a simple, safe, and reliable technique with a high diagnostic yield and is of particular value in submucosal, infiltrative, and ulceronecrotic tumours.
PMCID: PMC1378988  PMID: 1855680
18.  Prevalence of peptic ulcer in India: an endoscopic and epidemiological study in urban Kashmir. 
Gut  1989;30(7):930-934.
The prevalence of peptic ulcer disease in the general population of Kashmir, India, was determined by endoscopy in a randomly selected sample population of 2763 adults aged 15 years and above who were interviewed using a questionnaire. Of 239 persons with ulcer symptoms, 193 (80.7%) had an oesophagogastroduodenoscopy. A randomly selected 177 individuals from among the remaining population without ulcer symptoms, were also endoscoped. The point prevalence of peptic ulcer was 4.72% and the lifetime prevalence was 11.22%. The duodenal to gastric ulcer ratio was 17.1:1. Duodenal and gastric ulcer were common in men. The prevalence of peptic ulcer increased with age, with a peak prevalence of 28.8% in the 5th decade of life. Peptic ulcer was not related to socio-economic status. The prevalence of complications, such as bleeding, stenosis, or perforation were similar to those reported in the West.
PMCID: PMC1434311  PMID: 2788113
19.  Prevalence of biliary tract disease in India: a sonographic study in adult population in Kashmir. 
Gut  1989;30(2):201-205.
Sonography was used to investigate the prevalence of symptomatic and silent biliary tract disease, in free living urban population in Kashmir. A randomly drawn sample of 1695 subjects aged 15 years or above was interviewed by a questionnaire. Twenty six had previous cholecystectomies, all for gall stones. Ultrasonography was carried out on 1104 (65.1%). The responder rates for ultrasonography in men (64.3%) and in women (66.0%) were similar (p greater than 0.2). Gall stones were detected in 49 adults. Three of these had previous biliary symptoms. The prevalence of gall stones in adult population was 6.12% (men 3.07% and women 9.6%). The prevalence of gall stones rose with age in both sexes to a peak in the sixth decade prevalence of gall stones was significantly higher in age adjusted parous women than in nullipara. There was no correlation with obesity, diet, or socioeconomic status. Five subjects had sonographic appearances of the worm Ascaris lumbricodis in the bile ducts: and had previous biliary symptoms.
PMCID: PMC1378302  PMID: 2649414
20.  Role of specific immunoglobulin E to excretory-secretory antigen in diagnosis and prognosis of hookworm infection. 
Journal of Clinical Microbiology  1988;26(4):739-742.
Total immunoglobulin E (IgE) and specific IgE were assayed by a radioimmunosorbent test and a reverse enzyme immunoassay in patients with hookworm infections before and after treatment. A total of 77 subjects (30 patients with hookworm infections and 47 subjects as controls) were studied. Both specific and total IgE levels in serum and jejunal juice were raised in hookworm patients. There was a significant decrease in IgE levels after therapy. Total IgE levels were raised in other nematode infections, but specific IgE levels were low. The reverse enzyme immunoassay for specific IgE was highly specific (96%) and sensitive (100%) and may be used in the serodiagnosis of hookworm infections.
PMCID: PMC266433  PMID: 3284900
21.  Kinetics of lymphocyte subpopulation in intestinal mucosa of protein deficient Giardia lamblia infected mice. 
Gut  1986;27(4):386-391.
Kinetics of gut lymphocyte subpopulations were studied in normal and malnourished groups of mice infected with Giardia lamblia. The maximum parasite load was observed at second, third, and first week of postinfection in normal controls, moderate (8%) and severe (3%) protein deficient groups respectively. The number of G lamblia trophozoite in 3% protein deficient group was low compared with control groups. A significant increase in T cell population of intraepithelial lymphocytes and lamina propria in normal and moderate protein deficient groups was observed with the development of infection. It was less marked, however, in the severely malnourished group. Interplay of mucosal immune status with nutrition and G lamblia infection is discussed.
PMCID: PMC1433403  PMID: 3485552
22.  Direct and antibody dependent cell mediated cytotoxicity against Giardia lamblia by splenic and intestinal lymphoid cells in mice. 
Gut  1986;27(1):73-77.
Direct cytotoxicity and antibody dependent cell mediated cytotoxicity against Giardia lamblia trophozoites exhibited by splenic, intraepithelial and lamina propria lymphocyte populations isolated from G lamblia infected mice were studied. Different patterns of cytotoxicity were found. Intraepithelial lymphocytes showed a direct cytotoxic activity of 20.6 +/- 5.6% before infection. It was significantly higher on the 20th (p less than 0.01) and 30th (p less than 0.05) day postinfection. Lamina propria lymphocytes showed a significantly augmented level of both direct cytotoxicity and antibody dependent cell mediated cytotoxicity on the 20th and 30th postinfection days. Direct cytotoxicity by splenic lymphocytes remained unchanged during infection but antibody dependent cell mediated cytotoxicity was significantly increased.
PMCID: PMC1433184  PMID: 3949239

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