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Biomedical subjects

P Suresh

Publications and source records attributed to P Suresh.

At least 19 recordsLinked to original sources

Nonclinical toxicology study of recombinant-plasmid DNA anti-rabies vaccines.

The absence of standard guidelines from National and International regulatory agencies for the safety evaluation of biotechnology products challenges the ingenuity of toxicologists. At present, the development of standard pre-clinical toxicology protocols for such products is on an individual case basis. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed DNA based anti-rabies vaccine in India. The test compounds were DNA rabies vaccine [DRV (100 microg)] and combination rabies vaccine (CRV (100 microg DRV and 1/50 dose of cell culture vaccine)), intended for clinical use by intramuscular route on 1, 7, 14 and 28 day. As per the regular mandatory requirements, the study has been designed to undertake acute (single dose--10 days), sub-chronic (repeat dose--28 days) and chronic (intended clinical dose--120 days) toxicity tests using three dose levels viz. therapeutic, average (2 x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in Swiss Albino mice. The selection of the rodent model viz. Swiss Albino mice is based on affinity and rapid higher antibody response during the efficacy studies. Apart from physical, physiological, clinical, hematological and histopathology profiles of all target organs, the tier-I immunotoxicity parameters have also been monitored. There were no observational adverse effects even at levels of 10x therapeutic dose administration of DRV and CRV. The procedure also emphasizes on the designing of protocols for the products developed by recombinant technique.

Animals↗

Beneficial effect of copper supplementation on deposition of fluoride in bone in fluoride- and molybdenum-fed rabbits.

Fluorosis is a major public health problem in the world, including India. The present study was undertaken to investigate the role of molybdenum (Mo) in the deposition of fluoride (F) in bone and whether copper (Cu) supplementation has any alleviating role when F and Mo are ingested together. For this purpose, four groups of rabbits were used [control (C), fluoride (F), fluoride + molybdenum (F + Mo), and fluoride + molybdenum + copper (F + Mo + Cu)] to find out the effect of these treatments on various bone-related parameters like intact parathyroid hormone (iPTH), alkaline phosphatase and Cu in serum, hydroxyproline and calcium (Ca) in urine, and minerals (F, Cu, manganese, and zinc) in femur bone ash. Bone mineral content (BMC), bone mineral density (BMD) [by dual energy X-ray absorptiometry (DXA)], and strength of femur bones were also assessed. F content in the femur was significantly higher (P < 0.01) in all experimental groups compared to control group. Mo supplementation increased F deposition in femur bone in the F + Mo group, whereas supplementation of Cu reduced F deposition in the F + Mo + Cu group compared to the F + Mo and F groups. Levels of Cu in femurs of the F + Mo and F + Mo + Cu groups were significantly higher (P < 0.05, P < 0.01, respectively) than in the C group, although serum Cu was significantly lower in the F and F + Mo than the C and F + Mo + Cu groups. Magnesium levels in the F + Mo group were significantly higher (P < 0.05) than in the F and F + Mo + Cu groups. Cu supplementation in the F + Mo + Cu group increased deposition of zinc significantly (P < 0.05) compared to the F and F + Mo groups. Serum iPTH, alkaline phosphatase, and urinary hydroxyproline and Ca were significantly higher (P < 0.01) in the F and F + Mo than in the C and F + Mo + Cu groups. However, serum iPTH and urinary hydroxyproline were higher in the F + Mo group than the F group. Alkaline phosphatase was significantly higher in the F + Mo group than the F and F + Mo + Cu groups. Levels of serum Cu in the F and F + Mo groups were lower than in the C group, though serum Cu was significantly higher in the F + Mo + Cu than in all other groups. DXA analysis of femur bone indicated that BMD in the F + Mo group was significantly higher than in the F (P < 0.05), C (P < 0.01), and F + Mo + Cu (P < 0.05) groups. However, there was no significant difference in BMC among the groups. Bone strength was significantly higher (P < 0.05) in the F + Mo group than in the C group. Results of the present study show that ingestion of Mo with F does not create secondary Cu deficiency (due to increased excretion of Cu through urine). However, Cu concentration was decreased in serum in this group (F + Mo) compared to the C and F + Mo + Cu groups. Deposition of F in femur bone was more (22%) when it was given along with Mo compared to F alone, while F deposition in femur bone was less in the F + Mo + Cu group by 80% compared to the F group. Also, deposition of F in the F + Mo + Cu group was 120% less compared to the F + Mo group. The increase in F level due to Mo addition appears to be offset by supplementation with Cu. Supplementation with Cu showed a beneficial effect on bone resorption as well as bone formation.

Alkaline Phosphatase↗

A randomised, double-blind, parallel, placebo-controlled study to evaluate the efficacy of MF 5232 (Mucotrol), a concentrated oral gel wafer, in the treatment of oral mucositis.

OBJECTIVE: Oral mucositis is a major complication of cytotoxic chemotherapy and radiotherapy associated with significant morbidity, pain, odynophagia, dysgeusia and subsequent dehydration and malnutrition, and effective prophylaxis and/or treatment of this condition is essential. The currently available palliative treatment shows improvement only in patients with mild to moderate mucositis. The primary aim of this study was to compare the clinical efficacy of MF 5232 (Mucotrol), a concentrated oral polyherbal gel wafer formulation, with placebo in the management of chemoradiation-induced mucositis in cancer patients. PATIENTS AND DESIGN: In this randomised, double-blind, pilot study a total of 30 patients of either sex with chemoradiation-induced oral mucositis were randomised to receive MF 5232 (n = 15) or a matching placebo (n = 15) after food three times a day for 7-10 days. Patients were evaluated using validated and standardised scoring systems at baseline and after 7-10 days of treatment. RESULTS: There were 11 evaluable patients in each treatment group. There was a significant reduction in mean mucositis scores with MF 5232 as follows: WHO (from 3.0 to 1.8), Radiation Therapy Oncology Group (gross score: from 2.8 to 1.8; functional score: from 2.9 to 1.0), and Objective Scoring System (ulceration score: from 7.4 to 4.4; erythema score: from 13.7 to 7.0). There were no significant changes in scores for placebo recipients. The treatments were well tolerated, with the exception of two patients in the treatment group who reported a burning sensation in the mouth after dissolving the wafer. CONCLUSION: This pilot study provided positive evidence for the efficacy of MF 5232 therapy in chemoradiation-induced mucositis. This was probably a result of its local analgesic, antioxidant and immunomodulatory activity and wound-healing properties. Further in-depth analysis in a larger number of patients is required to confirm these positive results.

Administration, Oral↗

Detection of genetic polymorphism in the populations of brinjal shoot and fruit borer, Leucinodes orbonalis (Guenee).

In the present study six different populations of L. orbonalis were collected and subjected to analysis of genetic variability in terms of carboxylesterase isozyme pattern and DNA polymorphism using RAPD-PCR. Pattern of carboxylesterase revealed a similar isozyme cluster in the populations namely, sivaganga (population-3), dindigal (population-4), virudhunagar (population-5) and coimbatore (population-6). Similarly, the populations of L. orbonalis recorded 3 distinct randomly amplified polymorphic DNA markers in all populations grouped above. This pattern of genetic variability in the populations was also supported by the analysis of the similarity indices and UPGMA dendrogram.

Animals↗

Importance of adsorption (hole-filling) mechanism for hydrophobic organic contaminants on an aquifer kerogen isolate.

Sorption and desorption behaviors of four hydrophobic organic compounds (HOCs) were investigated for an isolated kerogen material from Borden aquifer material with total organic carbon of 0.021%. The solubility-normalized modified Freundlich equation and the combined linear and Polanyi-Dubinin (PD) equation can quite well describe the sorption or desorption isotherms. The partition component is estimated and compared using desorption data, dual-mode modeling, and the reported partition coefficients. The result suggests that the dual-mode modeling and the combined linear and PD modeling may overestimate the partitioning component. The partition component is not so important as assumed before in sorption of HOCs for the studied sorbent. As the fitted PD equation has an exponent parameter b' approaching 1, it is equivalent to the modified Freundlich equation. The small molecules 1,2-dichlorobenzene (DCB) and naphthalene (Naph) have higher adsorption volumes. The lower adsorption volumes for 1,3,5-trichlorobenzene (TCB) and phenanthrene (Phen) suggest that accessibility to the holes of kerogen by large HOC molecules is reduced. The desorption hysteresis is approximately constant for DCB when the relative aqueous concentration ranges from 0.0007 to 0.6, but for Phen is only obvious at higher relative aqueous concentrations. The varied sorption and desorption behaviors for DCB and Phen are satisfactorily explained by an adsorption/ hole filling mechanism and entrapment of some adsorbates in the kerogen matrix and by possible pore deformation mechanism at high concentrations.

Adsorption↗

Toxicity assessment of wild bean seed protein--arcelin on Asian armyworm, Spodoptera litura (Fabricius).

Arcelin, an anti-metabolic protein was purified from the seeds of wild bean, Lablab purpureus. The feeding assay containing arcelin at 5, 10 and 15 microg concentrations revealed no antifeedant effect against fifth instar larvae of S. litura. However, the enhanced activity of alpha- and beta-naphthyl esterases in the mid-gut samples of S. litura treated with arcelin suggests countermeasure against the toxic effect of arcelin.

Animals↗

Eye care for the critically ill.

PURPOSE: To evaluate the effectiveness and efficiency of an algorithm in the prevention of ocular surface disease in sedated and unconscious patients in the intensive care unit (ICU). METHODS: The eyes of all sedated and unconscious patients admitted to an ICU between September and December 1998 were managed according to an eye care algorithm. The applications of the preventive measures were assessed by a single observer twice weekly. The lid position, the presence and degree of keratopathy, sedation score, and the treatment received were documented at every assessment. RESULTS: Thirty-four patients were recruited for management according to the eye care algorithm over a period ranging from 1 to 28 days. Four patients were excluded because of failure by staff to adhere to the protocol. In 18 patients no active treatment was required. Out of six patients who had conjunctival exposure and were given ocular lubricants, four maintained clear corneas. No corneal or conjunctival staining was noted in two of the four patients whose lids required closure with Micropore tape for corneal exposure. Use of lid taping and lubricants prevented corneal abrasion in two patients who were prone ventilated. The prevalence of ocular surface abnormalities was 8.7 % where the algorithm was properly followed (23 patients). CONCLUSION: The proposed eye care algorithm appears to be effective in preventing ocular surface abnormalities in the sedated and unconscious patients in the ICU, and efficient in that it may reduce the workload required for critically ill patients.

Adult↗

Efficacy and tolerability of olanzapine in elderly patients with psychotic disorders: a prospective study.

Olanzapine is a novel antipsychotic effective in reducing positive and negative symptoms of schizophrenia and with a safe side-effect profile. Premarketing trials, however, included only a few elderly patients. Further data are needed regarding the effects of olanzapine in the elderly and those with comorbid medical illness. In this pilot study, 11 hospitalized patients (age range 60-85 years) who manifested symptoms of psychosis related to schizophrenia and schizoaffective disorders were treated with olanzapine (dose range, 5-20 mg/day). Efficacy and safety were assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), Extrapyramidal Symptom Rating Scale (ESRS), Mini-Mental State Examination (MMSE), Calgary Depression Scale For Schizophrenia (CDSS), EKG, physical examination, and various laboratory tests. Seven patients responded to treatment and all of them showed improvement in both positive and negative symptoms, with greater reduction in positive symptoms. Treatment was discontinued in 2 patients whose symptoms showed no improvement or worsened. The CGI showed significant improvement in 9 patients, remained the same in 1, and worsened in 1 patient. ESRS showed significant reduction from baseline to final visit. Of the 10 patients who cooperated for MMSE, 9 had improved scores. The CDSS showed significant reduction in scores from baseline to final visit. No significant changes were noted in laboratory tests, prolactin levels, EKG, and physical examination. Concomitant administration of lorazepam, carbamazepine, divalproex sodium, and lithium carbonate caused no adverse consequences. The reduction of positive and negative symptoms, lack of significant extrapyramidal symptoms and other side effects, and lack of any significant drug interaction suggest that olanzapine may be a safe and effective antipsychotic medication in the elderly.

Aged↗

Thyroid function screening in acute geropsychiatric admissions.

Thyroid function abnormalities have been associated with psychiatric illness. Even though it is a common practice to assess thyroid function in geropsychiatric patients, a literature search for the past 10 years did not reveal any published studies of assessments of thyroid function abnormalities in acute geropsychiatric populations. A retrospective chart review of 197 acute geropsychiatric inpatients and 14 comparison group patients showed that 40 geropsychiatric patients and 2 comparison group patients had abnormal thyroid function tests (TFfs). The most common abnormality was elevated triiodothyronine uptake (T3U), which was noted in 19 female and 13 male geropsychiatric patients. The difference in the prevalence of TFT abnormalities between the geropsychiatric patients and the comparison group subjects was not statistically significant. Both T3U and free thyroxine index (FTI) were significantly higher in the female geropsychiatric patients than in the female comparison group patients. The abnormalities in T3U and FTI in this study group may be related to an increased prevalence of unidentified systemic illness or to the presence of chronically poor nutrition.

Aged↗

Graft failure in human donor corneas due to transmission of herpes simplex virus.

AIM: To report the clinical consequences of contamination of human donor corneas by herpes simplex virus (HSV) in organ culture. METHODS: Two patients without previous history of ocular HSV infection underwent penetrating keratoplasty (PK), one for keratoconus and the other for Fuchs' endothelial dystrophy. One patient suffered primary graft failure while the other developed a persistent epithelial defect, ultimately resulting in graft failure. Viral culture of swabs taken from both corneas during the early postoperative period was undertaken. The failed donor corneas were examined histopathologically by immunohistochemistry (IHC) for HSV-1 antigens, transmission electron microscopy (TEM), and by polymerase chain reaction (PCR) for HSV DNA. Both failed corneas were replaced within 6 weeks of the initial surgery. The records of the fellow donor corneas were also examined for evidence of infection. RESULTS: HSV was cultured from both corneas during the early postoperative period. Histology of both donor corneas demonstrated a thickened corneal stroma with widespread necrosis of keratocytes and loss of endothelial cells. IHC showed keratocytes positive with antibodies to HSV-1 antigens. TEM demonstrated HSV-like viral particles within degenerating keratocytes. PCR performed on the failed corneal grafts was positive for HSV-1 DNA, whereas PCR performed on the excised host corneal buttons was negative in both patients. Records of the fellow donor corneas showed that one cornea was successfully transplanted into another recipient after 18 days in organ culture, whilst the other was discarded because of extensive endothelial cell necrosis noted after 15 days in organ culture. CONCLUSION: HSV within a donor cornea may cause endothelial destruction in organ culture and both primary graft failure and ulcerative keratitis after transplantation. Endothelial necrosis of a donor cornea in culture also raises the possibility of HSV infection within the fellow cornea.

Adult↗

Protection from Cryptosporidium parvum infection by gammadelta T cells in mice that lack alphabeta T cells.

BACKGROUND AND PURPOSE: Cryptosporidium parvum establishes a parasitic relationship with epithelial cells of the intestine. Infection with this protozoan is resolved in the immunocompetent host, but persistent life-threatening infection develops in the immunocompromised host. We propose that gammdelta T cells in the intestinal mucosa play a role in immunity to C. parvum. METHODS: Intestinal intra-epithelial lymphocyte and lamina propria T-cell subsets were examined in mice infected with C. parvum. The mice are homozygous for a deletion of the TCRalpha chain gene, TCRalpha(-/-) and, therefore, lack conventional alphabeta T cells, but retain a population of T cells with gammadelta T-cell receptors. To examine the contribution of gammadelta T cells to immunity, these mice were treated with monoclonal antibody GL3-3A, specific for this T-cell receptor, then were inoculated with C. parvum oocysts. Lymphocyte subsets and hematoxylin and eosin (H&E)-stained intestinal sections from untreated mice were compared with those from mice treated with either a low dose of GL3-3A for 6 weeks, or a high dose of GL3-3A for 16 weeks. RESULTS: The proportion of gammadelta T cells in the lamina propria increased in infected mice. In mice treated with a low dose of GL3-3A, a population of gammadelta T cells that had characteristics of activated cells, was still evident 6 weeks after inoculation. No C. parvum developmental forms were identified in the intestinal sections of mice under these conditions. However, TCRalpha(-/-) mice treated with a high dose of GL3-3A were depleted of gammadelta T cells, and 50% of the mice were infected with C. parvum. CONCLUSIONS: The gammadelta T cells contribute to protection against C. parvum infection. In the absence of conventional T cells, activation of intestinal gammadelta T cells may prevent infection with this organism.

Animals↗

Experience with the atypical antipsychotics--risperidone and olanzapine in the elderly.

There is paucity of published data regarding controlled trials with risperidone and olanzapine in elderly psychotic patients. Medical records of 151 hospitalized geropsychiatric patients (risperidone patients n = 114 and olanzapine patients n = 37) were analyzed for demographic data, target symptoms, doses, effects, side effects, comorbid medical conditions and concurrent medications. The mean age of the patients was 71 years. The male: female ratio was essentially the same for both groups. The mean daily dose was 3 mg for risperidone and 10 mg for olanzapine. 78% of the risperidone group and 75% of the olanzapine group appear to have responded to treatment. The discontinuation rates of medication was the same in both groups (22%). Adverse events were reported in 16-17% in both groups. It appears from this study that both risperidone and olanzapine are relatively safe and effective in geropsychiatric patients with comorbid medical illnesses. Controlled studies and head-to-head comparison studies are recommended.

Aged↗

Ocular surface disease in intensive care unit patients.

PURPOSE: To assess the prevalence and natural history of ocular surface disease in patients in an intensive care unit (ICU) and to identify any predisposing factors in order to improve eye care management protocols. METHODS: The eyes of all patients admitted to an ICU between February and May 1998 were examined at least weekly. The eyelid position, presence of conjunctival oedema, degree of keratopathy and sedation score were documented at every assessment. RESULTS: Twenty-six patients in an ICU were followed throughout their stay, which ranged from 3 days to 10 weeks. Eleven patients (42%) had some degree of keratopathy, which was detected in the majority in the first week of their stay. The presence of ocular surface disease was closely correlated with the degree of lagophthalmos, which in turn is closely related to the depth of sedation or paralysis. CONCLUSIONS: In this first ever longitudinal study it was found that assessment of lid position in ICU patients is the single most important observation to be carried out. A management algorithm derived from this evidence is based on daily observation and selective lid taping and shows encouraging early results.

Adult↗

Flavin metabolism during respiratory infection in mice.

Previous control studies carried out in children showed that respiratory infection alters riboflavin metabolism and leads to excessive urinary losses of the vitamin. In order to understand the nature of biochemical changes in riboflavin metabolism during respiratory infection, a study was carried out using the mouse as the experimental model, and Klebsiella pneumoniae as the infective organism. Mice were fed on either a low (0.5 mg/kg)- or high (13.3 mg/kg)-riboflavin semi-synthetic diet. Infection resulted in a 5-6-fold higher excretion of riboflavin in the urine of mice fed on the low-riboflavin diet. Higher erythrocyte FAD levels and lower liver FAD levels were also observed during infection. Of the four enzymes involved in the synthesis and breakdown of the flavin coenzymes studied, the activity of hepatic flavokinase (ATP: riboflavin 5'-phosphotransferase; EC 2.7.1.26) was significantly lower, and that of FAD synthetase (ATP: FMN adenylyltransferase; EC 2.7.7.2) was higher during riboflavin restriction and infection. The activity of FMN (acid) phosphatase (EC 3.1.3.2) was unchanged, whereas FAD (nucleotide) pyrophosphatase (EC 3.6.1.9) activity was significantly higher both with the low-riboflavin diet and during infection. Thyroid hormone is known to modulate flavokinase activity and, hence, thyroid status was assessed. Plasma triiodothyronine (T3) levels were not affected, but thyroxine levels were lower in the mice fed on the low-riboflavin diet. However, plasma T3 was significantly lower during infection, suggesting a mechanistic role for the hormone in the reduction of flavokinase activity.

Animals↗

Comparative evaluation of several techniques for purification of Cryptosporidium parvum oocysts from rat feces.

Three methods of isolating Cryptosporidium parvum oocysts from rat feces were evaluated. Oocysts were initially isolated by sucrose density gradient centrifugation. They were further purified by passage through a glass bead column or a Percoll gradient or by dialysis. Although oocysts recovered from the glass bead column and by dialysis were relatively free of fecal debris, only oocysts recovered from the Percoll gradient were free of bacteria. Recovered oocysts retained their antigenicity and infectivity. The ability to effectively recover oocysts from rat feces suggests that the laboratory rat may be a convenient substitute for ruminants in the propagation and maintenance of C. parvum oocysts for in vitro and in vivo use.

Animals↗

Effect of passively administered immunoglobulin G on the colonization and clearance of Bordetella avium in turkeys.

This study was conducted to detect the effect of parenterally administered immunoglobulin isotype G (IgG) on the colonization and clearance of Bordetella avium at the tracheal surface in young turkeys. In two separate experiments, 3-week-old turkeys were infected with B. avium either after or before IgG administration. Comparisons were made between a control group which received an irrelevant IgG (specific for keyhole limpet hemocyanin [KLH]) and the experimental group which received a B. avium-specific IgG. When given before the bacteria, IgG reduced the numbers of colony-forming units (CFUs) in the trachea. As a supplement to non-specific respiratory defense mechanisms, B. avium-specific IgG also appears to inhibit colonization of the tracheal mucosa. In a second experiment designed to study the role of IgG in bacterial clearance, administration of B. avium-specific IgG after bacterial inoculation significantly reduced the number of CFUs on the tracheal surface. These studies support the role of B. avium-specific IgG in resistance to and recovery from B. avium infection.

Animals↗