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Biomedical subjects

R Chandrasekaran

Publications and source records attributed to R Chandrasekaran.

At least 19 recordsLinked to original sources
PubMed2006

Gender differences in medically serious suicide attempts: a study from south India.

Studying gender differences in suicidal behaviour is important in developing specific need-based service provisions. We aimed to identify gender-specific characteristics associated with attempted suicide in a general hospital sample in south India. Two hundred and three patients admitted to medical wards following suicide attempts were assessed using a detailed clinical interview, measures of suicide intent (Suicide Intent Scale), lethality (Risk Rescue Rating), depression (Montgomery-Asberg Depression Rating Scale) and recent stress (Presumptive Stressful Life Events Scale). The majority of men attempting suicide were single. Men were more likely to use organophosphate poisons in their attempt to kill themselves and had higher rates of mental illness than women. As compared with men, women were more likely to come from rural areas, had a lower educational status, and had lower rates of employment outside the home. In women, the most common method of suicide attempt was by using plant poisons. Suicide attempt by self-immolation was significantly higher among women. Men had higher suicidal intent than women, although lethality, depression and stress were comparable between the genders. Rural women were more disadvantaged in education; however, in urban areas, men had higher psychiatric morbidity. Our results emphasise the need for a gender-specific approach among people who have attempted suicide.

Adolescent↗
PubMed2006

Characteristics of high intent suicide attempters admitted to a general hospital.

BACKGROUND: Suicide intent is a strong predictor of repetition of attempts and subsequent suicide. This study aimed to compare socio-demographics, clinical factors and method of attempt in high and low intent suicide attempters. METHOD: All patients admitted following attempted suicide to a teaching hospital were interviewed. Socio-demographic information, details of the attempt and psychiatric diagnosis were recorded. Scales for assessing suicide intent, lethality, recent life-events and depression were administered. Comparison between high intent and low intent groups were done to identify the characteristics of patients who had high suicidal intent. RESULTS: The sample comprised 203 patients, 84 of whom were classified as high intent attempters using the Suicide Intent Scale. The high intent group were significantly more likely to be male (p = 0.01), of single marital status (p = 0.04), have a psychiatric diagnosis, especially depression (p = 0.001) and use self immolation to attempt suicide (p = 0.001). Patients with high intent had significantly higher lethality (p = 0.001) and recent stressful life-event scores (p = 0.001). CONCLUSIONS: High intent suicide attempts are associated with distinct socio-demographic profiles and psychiatric morbidity. Routine assessment of intent may help to identify individuals with high risk, who can be offered targeted interventions.

Adolescent↗
PubMed2004

The combination of pamidronate and calcitriol reverses particle- and TNF-alpha-induced altered functions of bone-marrow-derived stromal cells with osteoblastic phenotype.

Periprosthetic bone loss after total joint arthroplasty is a major clinical problem resulting in aseptic loosening of the implant. Among many cell types, osteoblasts play a crucial role in the development of peri-implant osteolysis. In this study, we tested the effects of calcitriol (1alpha,25-dihydroxy-vitamin-D3) and the bisphosphonate pamidronate on titanium-particle- and TNF-alpha-induced release of interleukin-6 and suppression of osteoblast-specific gene expressions in bone-marrow-derived stromal cells with an osteoblastic phenotype. We monitored the expression of procollagen alpha1[1], osteocalcin, osteonectin and alkaline phosphatase mRNAs by Northern blots and real-time reverse transcription and polymerase chain reaction analyses. The release of various cytokines was also analysed by ELISA. We found that calcitriol or pamidronate could only partially recover the altered functions of osteoblasts when added alone. Only a combination of these compounds restored all the tested functions of osteoblasts. The local delivery of these drugs may have therapeutic potential to prevent or to treat periprosthetic osteolysis and aseptic loosening of implants.

Adult↗
PubMed2002

Acute polymorphic psychotic disorder: diagnostic stability over 3 years.

OBJECTIVE: Acute polymorphic psychotic disorder without symptoms of schizophrenia (APPD) in ICD-10 is unique in many characteristics. This study aimed at investigating the diagnostic stability of APPD over 3 years. METHOD: Forty-five patients with first episode APPD were followed up and assessed at regular intervals over a period of 3 years. RESULTS: Thirty-two patients were females. Average age of the sample was 26.9 years. Thirty-three cases retained their index diagnosis of APPD, while 12 cases required diagnostic revision: 10 to bipolar affective disorder and the rest to unspecified non-organic psychosis. Shorter duration of illness (<1 month) and abrupt onset (<48 h) predicted a stable diagnosis of APPD. CONCLUSION: APPD is a relatively stable diagnosis and argues for a distinct diagnostic entity.

Acute Disease↗
PubMed2002

Natural history and prognostic factors of diabetic nephropathy in type 2 diabetes.

BACKGROUND: The causes and mechanisms of increased mortality of patients with diabetic nephropathy are unclear, and its natural history is poorly understood. AIM: To evaluate risk factors for mortality in type 2 diabetic patients with nephropathy. DESIGN: Retrospective study of clinical and biochemical parameters in diabetic nephropathic patients and controls sampled from a secondary care register. METHODS: We studied 170 type 2 diabetic patients (from 1987 to 1995) with nephropathy (proteinuria >0.5 g/24 h) and 170 non-nephropathic patients. Follow-up was until death or December 1997. Details of demographics, clinical and treatment history were obtained from medical records. RESULTS: Mean follow-up was 5.3 years. Of the patients with nephropathy at baseline, 63 (37%) died compared with 14 (8%) non-nephropathic patients (chi(2)=53.8, p<0.0001). Age- and sex-adjusted all-cause mortality rates were 8.1 (6.4, 9.8) and 1.4 (0.5, 2.2) deaths per 100 person-years, respectively (rate ratio 5.8). Forty-four patients (57%) died from cardiovascular causes (rate ratio 5.4). Mortality was directly proportional to degree of proteinuria: 0.5-2 g/24 h, 4.6 (2.9-7.1); >2 g/24 h, 9.9 (7.3-13.5) per 100 patient-years. A 36% (5-78%) excess risk of mortality was observed for each log unit increase in proteinuria. Multivariate Cox regression analyses confirmed a five-fold excess risk for all-cause and cardiovascular mortality in patients with nephropathy compared with those without. This was independent of other risk factors including baseline age [5% (1-8%)/year], creatinine [2.5 (1.12-5.6)/10 micromol/l] and glycaemic control (HbA(1c)) [15% (1-31%) per 1% rise]. CONCLUSIONS: Proteinuria is a potentially preventable and reversible risk factor associated with high mortality in type 2 diabetic patients. Prevention of the development of overt nephropathy and improvement in diabetes control may reduce mortality in these patients.

Aged↗
PubMed2001

Three-dimensional structure of the sodium salt of iota-carrageenan.

The three-dimensional structure of the sodium salt of iota-carrageenan has been determined by using X-ray diffraction data collected from its polycrystalline and oriented fibers. The molecule forms a half-staggered, parallel, threefold, right-handed double helix that is stabilized by interchain hydrogen bonds from 2- and 6-hydroxyl groups in the galactosyl units. Three helices are organized in a trigonal unit cell, of dimensions a=24.02 and c=12.93 A, with a lateral separation of 13.9 A for each pair. Both 2- and 4-sulfate groups are essential in helix-helix interactions that are mediated only by sodium ions and water molecules.

Carrageenan↗
PubMed2001

Antibody-induced shedding of CD44 from adherent cells is linked to the assembly of the cytoskeleton.

CD44 is a widely expressed integral membrane glycoprotein that serves as a specific adhesion receptor for the extracellular matrix glycosaminoglycan hyaluronan. CD44 participates in a variety of physiological and pathological processes through its role in cell adhesion. Under appropriate conditions, the ectodomain of CD44 is proteolytically removed from the cell surface. In this study we show that excessive CD44 shedding can be induced in mouse fibroblasts and monocytes upon exposure of these cells to a CD44-specific Ab immobilized on plastic, whereas treatment with phorbol ester induces significantly enhanced CD44 release from the monocytes only. CD44 shedding proceeds normally in fibroblasts and monocytes deficient in TNF-alpha converting enzyme (TACE), a sheddase involved in the processing of several substrates. Conversely, activation of the CD44 protease has no effect on the release of TNF-alpha from TACE-expressing cells, although the same metalloprotease inhibitor effectively blocks both TACE and the CD44 sheddase. Concomitant with anti-CD44 Ab- or phorbol ester-induced CD44 shedding, dramatic changes are observed in cell morphology and the structure of the actin cytoskeleton. Disruption of actin assembly with cytochalasin reduces CD44 shedding, but not the release of TNF-alpha. Moreover, pharmacological activation of Rho family GTPases Rac1 and Cdc42, which regulate actin filament assembly into distinct cytoskeletal structures, has a profound effect on CD44 release. We conclude that the CD44 sheddase and TACE are distinct enzymes, and that Ab- and phorbol ester-enhanced cleavage of CD44 is controlled in a cell type-dependent fashion by Rho GTPases through the cytoskeleton.

ADAM Proteins↗
PubMed2001

Variations in susceptibility to proteoglycan-induced arthritis and spondylitis among C3H substrains of mice: evidence of genetically acquired resistance to autoimmune disease.

OBJECTIVE: To identify and screen the level of arthritis susceptibility in C3H murine strains known to be resistant to proteoglycan (aggrecan)-induced arthritis, and to measure and correlate various immunologic and inflammatory parameters with susceptibility to either arthritis or spondylitis in various C3H substrains. METHODS: Mice of 10 C3H substrains (subcolonies) were immunized with cartilage proteoglycan (aggrecan) for induction of arthritis. Animals were assessed for clinical symptoms, and the peripheral joints and spine were studied by histologic methods. Proteoglycan-specific T cell responses (T cell proliferation and production of interleukin-2 [IL-2], interferon-y, and IL-4) and the B cell response to lipopolysaccharide (LPS) were measured in spleen cell cultures. Serum levels of heteroantibodies and autoantibodies as well as various cytokines (IL-6, IL-10, IL-12, and tumor necrosis factor alpha) and soluble CD44 were determined by enzyme-linked immunosorbent assay. RESULTS: Immunization with cartilage proteoglycan induced severe arthritis in the C3H/HeJCr substrain (95-100% incidence), whereas the original parent mice of the C3H/HeJ colony were resistant to proteoglycan (aggrecan)-induced arthritis. Furthermore, the progressive polyarthritis that is characteristic in susceptible C3H/HeJCr mice was accompanied by progressive inflammation around the spine. In subsequent experiments, 10 different C3H colonies with largely identical genetic backgrounds (all originating from the National Institutes of Health or Jackson Laboratory) exhibited extreme differences in susceptibility. Although none of the laboratory findings, including LPS hyporesponsiveness, immunologic parameters, and inflammatory markers, showed a correlation with susceptibility or resistance in the C3H/HeJCr and C3H/HeJ substrains, respectively, significant differences were found when all arthritic C3H mice were compared with all nonarthritic animals, regardless of their substrain origin. CONCLUSION: Because many of the C3H substrains lost arthritis susceptibility or acquired resistance, our results suggest that a preferred site for a mutation(s) in a gene(s) in a relatively upstream position of the inflammatory cascade is present. This is the first autoimmune model that exhibits extreme differences in arthritis susceptibility in the same murine strain, and is therefore a valuable tool for identification of arthritis-susceptible (or arthritis-suppressive) genes.

Animals↗
PubMed2001

Embryotoxicity and teratogenicity studies of an ayurvedic contraceptive--pippaliyadi vati.

An ayurvedic contraceptive--pippaliyadi vati, containing equal parts of powdered seeds or fruit berries of Embelia ribes, fruit of Piper longum and borax powder was fed orally to two groups of pregnant rats: 2.5 times to one and five times to the other; the recommended dose for humans. The foetuses of mothers fed with pippaliyadi had low birth weights and were smaller in length. The mothers gained less weight during gestation. Developmental defects of soft tissues and skeletons were analyzed. There were instances of herniation of the intestines into the umbilical cord in foetuses of mothers who were administered pippaliyadi. The control and the gum acacia groups did not show such herniation.

Abnormalities, Drug-Induced↗
PubMed2001

The effects of particulate wear debris, cytokines, and growth factors on the functions of MG-63 osteoblasts.

BACKGROUND: Particle-challenged cells release cytokines, chemokines, and eicosanoids, which contribute to periprosthetic osteolysis. The particle-induced activation of macrophages and monocytes has been extensively studied, but only limited information is available on the response of osteoblasts to particulate wear debris. This study examines the effects of particulate wear debris, proinflammatory cytokines, and growth factors on osteoblast functions. METHODS: MG-63 osteoblasts were treated with metal particles (titanium, titanium alloy, and chromium orthophosphate) or polymeric particles (polyethylene and polystyrene) of phagocytosable sizes or were treated with exogenous cytokines and growth factors. The kinetics of particle phagocytosis and the number of engulfed particles were assessed with use of fluoresceinated particles. Cell proliferation was determined according to [3H]-thymidine incorporation, and cell viability was determined by either fluorescein diacetate uptake or trypan blue exclusion. Expressions of osteoblast-specific genes were quantified with Northern blot hybridization, and the secretions of osteoblast-specific proteins and cytokines were analyzed by enzyme-linked immunosorbent assays. RESULTS: MG-63 osteoblasts phagocytosed particles and became saturated after twenty-four hours. A maximum of forty to sixty particles per cell were phagocytosed. Each type of particle significantly suppressed procollagen alpha1[I] gene expression (p<0.05), whereas other osteoblast-specific genes (osteonectin, osteocalcin, and alkaline phosphatase) did not show significant changes. Particle-stimulated osteoblasts released interleukin-6 (p<0.05) and a smaller amount of transforming growth factor-beta1. Particles reduced cell proliferation in a dose-dependent manner without affecting cell viability (p<0.05). Exogenous tumor necrosis factor-alpha also enhanced the release of interleukin-6 (p<0.01) and transforming growth factor-beta1 (p<0.05), whereas the secretion of transforming growth factor-beta1 was increased by insulin-like growth factor-I and prostaglandin E2 as well. Insulin-like growth factor-I and transforming growth factor-beta1 significantly increased procollagen alpha1[I] gene expression in osteoblasts (p<0.05), while tumor necrosis factor-alpha and prostaglandin E2 significantly suppressed procollagen alpha1[I] gene expression (p<0.01). In contrast, neither exogenous nor endogenous interleukin-6 had any effect on other cytokine secretion, on proliferation, or on procollagen alpha1[I] gene expression. The transcription inhibitor actinomycin D reduced both procollagen alpha1[I] transcription and interleukin-6 production. Inhibitors of protein synthesis (cyclohexamide) and intracellular protein transport (brefeldin A and monensin) blocked the release of interleukin-6, but none of these compounds influenced the suppressive effect of titanium on procollagen alpha1[I] gene expression. CONCLUSIONS: MG-63 osteoblasts phagocytose particulate wear debris, and this process induces interleukin-6 production and suppresses type-I collagen synthesis. Osteoblast-derived interleukin-6 may induce osteoclast differentiation and/or activation, but the resorbed bone cannot be replaced by new bone because of diminished osteoblast function (reduced type-I collagen synthesis). Exogenous cytokines (tumor necrosis factor-alpha and interleukin-1beta), growth factors (insulin-like growth factor-I and transforming growth factor-beta1), and prostaglandin E2 can modify particulate-induced alterations of osteoblast functions.

Biocompatible Materials↗
PubMed2000

Structure of poly (dT).poly (dA).poly (dT).

The molecular structure of poly (dT).poly (dA).poly (dT) has been determined and refined using the continuous x-ray intensity data on layer lines in the diffraction pattern obtained from an oriented fiber of the DNA. The final R-value for the preferred structure is 0.29 significantly lower than that for plausible alternatives. The molecule forms a 12-fold right-handed triple-helix of pitch 38.4 A and each base triplet is stabilized by a set of four Crick-Watson-Hoogsteen hydrogen bonds. The deoxyribose rings in all the three strands have C2'-endo conformations. The grooveless cylindrical shape of the triple-helix is consistent with the lack of lateral organization in the fiber.

DNA↗
PubMed2000

Structure of Poly (U).poly (A).poly (U).

The molecular structure of poly (U).poly (A).poly (U) has been determined and refined using the continuous x-ray intensity data on layer lines in the diffraction pattern obtained from an oriented fiber of the RNA. The final R-value for the preferred structure is 0.24, far lower than that for the plausible alternatives. The polymer forms an 11-fold right-handed triple-helix of pitch 33.5A and each base triplet is stabilized by Crick-Watson-Hoogsteen hydrogen bonds. The ribose rings in the three strands have C3'-endo, C2'-endo and C2'-endo conformations, respectively. The helix derives additional stability through systematic interchain hydrogen bonds involving ribose hydroxyls and uracil bases. The relatively grooveless cylindrical shape of the triple-helix is consistent with the lack of lateral organization.

DNA↗
PubMed2000

Structure of poly (I).poly (A).poly (I).

The molecular structure of poly (I).poly (A).poly (I) has been determined and refined using the continuous intensity data on layer lines in the x-ray diffraction pattern obtained from an oriented fiber of this polymorphic RNA complex. The polymer forms a 12-fold right-handed triple-helix of pitch 39.7A and each base-triplet is stabilized by quasi Crick-Watson-Hoogsteen hydrogen bonds. The ribose rings in all the three strands have C3'-endo conformations. The final R-value for this best structure is 0.24 and the x-ray fit is significantly superior to all the alternative structures where the different chains might have different furanose conformations. This all-purine triple-helix, counter-intuitively, has a diameter roughly 3A shorter than that of DNA and RNA triple-helices containing a homopurine and two complementary homopyrimidine strands. Its compact, grooveless cylindrical shape is consistent with the lack of lateral organization.

Adenine↗
PubMed2000

Particulate wear debris activates protein tyrosine kinases and nuclear factor kappaB, which down-regulates type I collagen synthesis in human osteoblasts.

Particulate wear debris generated mechanically from prosthetic materials is phagocytosed by a variety of cell types within the periprosthetic space including osteoblasts, which cells with an altered function may contribute to periprosthetic osteolysis. Exposure of osteoblast-like osteosarcoma cells or bone marrow-derived primary osteoblasts to either metallic or polymeric particles of phagocytosable sizes resulted in a marked decrease in the steady-state messenger RNA (mRNA) levels of procollagen alpha1[I] and procollagen alpha1[III]. In contrast, no significant effect was observed for the osteoblast-specific genes, such as osteonectin and osteocalcin (OC). In kinetic studies, particles once phagocytosed, maintained a significant suppressive effect on collagen gene expression and type I collagen synthesis for up to five passages. Large particles of a size that cannot be phagocytosed also down-regulated collagen gene expression suggesting that an initial contact between cells and particles can generate gene responsive signals independently of the phagocytosis process. Concerning such signaling, titanium particles rapidly increased protein tyrosine phosphorylation and nuclear transcription factor kappaB (NF-kappaB) binding activity before the phagocytosis of particles. Protein tyrosine kinase (PTK) inhibitors such as genistein and the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the suppressive effect of titanium on collagen gene expression suggesting particles suppress collagen gene expression through the NF-kappaB signaling pathway. These results provide a mechanism by which particulate wear debris can antagonize the transcription of the procollagen alpha1[I] gene in osteoblasts, which may contribute to reduced bone formation and progressive periprosthetic osteolysis.

Cell Survival↗