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Biomedical subjects

G Joshi

Publications and source records attributed to G Joshi.

13 recordsLinked to original sources

In vivo protection by the xanthate tricyclodecan-9-yl-xanthogenate against amyloid beta-peptide (1-42)-induced oxidative stress.

Considerable evidence supports the role of oxidative stress in the pathogenesis of Alzheimer's disease. One hallmark of Alzheimer's disease is the accumulation of amyloid beta-peptide, which invokes a cascade of oxidative damage to neurons that can eventually result in neuronal death. Amyloid beta-peptide is the main component of senile plaques and generates free radicals ultimately leading to neuronal damage of membrane lipids, proteins and nucleic acids. Therefore, interest in the protective role of different antioxidant compounds has been growing for treatment of Alzheimer's disease and other oxidative stress-related disorders. Among different antioxidant drugs, much interest has been devoted to "thiol-delivering" compounds. Tricyclodecan-9-yl-xanthogenate is an inhibitor of phosphatidylcholine specific phospholipase C, and recent studies reported its ability to act as a glutathione-mimetic compound. In the present study, we investigate the in vivo ability of tricyclodecan-9-yl-xanthogenate to protect synaptosomes against amyloid beta-peptide-induced oxidative stress. Gerbils were injected i.p. with tricyclodecan-9-yl-xanthogenate or with saline solution, and synaptosomes were isolated from the brain. Synaptosomal preparations isolated from tricyclodecan-9-yl-xanthogenate injected gerbils and treated ex vivo with amyloid beta-peptide (1-42) showed a significant decrease of oxidative stress parameters: reactive oxygen species levels, protein oxidation (protein carbonyl and 3-nitrotyrosine levels) and lipid peroxidation (4-hydroxy-2-nonenal levels). Our results are consistent with the hypothesis that modulation of free radicals generated by amyloid beta-peptide might represent an efficient therapeutic strategy for treatment of Alzheimer's disease and other oxidative-stress related disorders. Based on the above data, we suggest that tricyclodecan-9-yl-xanthogenate is a potent antioxidant and could be of importance for the treatment of Alzheimer's disease and other oxidative stress-related disorders.

Aldehydes↗

An investigation of paediatric dentists' attitudes towards parental accompaniment and behavioural management techniques in the UK.

OBJECTIVE: Good behavioural management techniques are essential for treating children. Recent research has investigated parental and paediatric attitudes towards various behavioural management techniques. However, in the UK, very little is known about paediatric attitudes towards such issues. Accordingly, the aim of this investigation was to conduct a survey in order to provide insight into the current thinking of paediatric dentists across the UK. STUDY DESIGN: A questionnaire was developed for this study on the basis of previous surveys investigating the attitudes of paediatric dentists towards the use of various behavioural management techniques in Australia and the USA. Areas covered in the questionnaire included: attitudes towards parental accompaniment; attitudes regarding parental expectations; and attitudes towards the use of various different child management techniques. The questionnaire was sent out to all registered members of the British Society of Paediatric Dentistry (n = 304). RESULTS: 245 responses (80.5%) were returned, of which 218 provided valid and useable information (72%). A majority of 80% of respondents supported parental accompaniment of the child during the course of treatment. Separate analysis of variance (ANOVA) procedures revealed significant differences between acceptability of parental accompaniment and the year in which dentists had qualified (P < 0.05). More recently qualified dentists were less accepting of parental accompaniment. Only a minority of dentists reported feeling pressured by parental expectations with regard to their child's treatment. However, an independent sample t-test revealed that male dentists experienced greater perceived conflict between dental and parental expectations, than female dentists (P < 0.05). In terms of specific behavioural management techniques, the most favoured was 'tell-show-do' with 87% of respondents citing this as their most commonly used method. Least acceptable were 'hand over mouth' techniques, followed closely by active restraint and papoose board. CONCLUSION: In general, paediatric dentists in the UK favoured less 'restraining' methods of behavioural management. There was widespread support for parental accompaniment in the dental operatory and a desire to work in participation with parents in order to facilitate the child's good behaviour and more effective dental treatment. Further studies comparing the effectiveness of various techniques used with regard to treatment time and clinical outcomes, are now required.

Adult↗

Localization of putative calcium-responsive regions in the rat BDNF gene.

Brain-derived neurotrophic factor (BDNF) has potent trophic and protective actions on CNS neurons, including mesencephalic dopaminergic neurons, ventral forebrain cholinergic neurons and spinal motor neurons. To evaluate the effects of calcium and other second messengers on BDNF gene transcription, C6 glioma cells were treated for 4 h with the calcium ionophore A23187, forskolin + isobutyl-methyl-xanthine (IBMX), or the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate. Semi-quantitative RT-PCR analysis revealed that A23187 treatment increased BDNF transcripts containing the protein coding exon by 4.4-6.4-fold. Alternate BDNF transcripts were elevated to varying degrees after treatment with this ionophore and a subset of these transcripts was elevated following forskolin + IBMX treatment. When co-incubated with the RNA polymerase inhibitor, actinomycin D, A23187-induced increases were reduced or abolished, suggesting that calcium-mediated regulation of BDNF mRNA expression occurs at transcriptional as well as post-transcriptional levels. Transient transfection experiments employing reporter constructs containing serial 5' deletions of alternate BDNF promoters suggested that A23187-induced elevations in BDNF exon 1b, 1d and 1e containing transcripts are mediated by putative calcium-responsive regions flanking all three of these exons.

Animals↗

10-Formyltetrahydrofolate synthetase. Evidence for a conformational change in the enzyme upon binding of tetrahydropteroylpolyglutamates.

The 10-formyltetrahydrofolate synthetase domain of the trifunctional enzyme C1-tetrahydrofolate synthase appears to undergo a conformational change in the presence of tetrahydropteroylpolyglutamates, MgATP, and ammonium ion. The binding of these ligands increases the denaturation temperature of the enzyme by 12 degrees C, abolishes the cold lability of the enzyme, and alters its susceptibility to digestion by chymotrypsin. The results suggest that a conformational change is dependent upon binding of the third glutamate residue of tetrahydropteroylpolyglutamates and the beta-phosphoryl group of MgATP. The Km values for MgATP and formate are lowered 3.6- and 520-fold, respectively, when tetrahydropteroyltriglutamate is used as the substrate in place of tetrahydropteroylmonoglutamate. A sensitive coupled assay involving C1-tetrahydrofolate synthase and serine hydroxymethyltransferase was developed to determine the activity of 10-formyltetrahydrofolate synthetase. The assay gives linear rates with the tetrahydropteroylpolyglutamates as substrates but not with the monoglutamate form.

Adenosine Triphosphate↗

A cell line secreting stimulating factors for CFU-GEMM culture.

The multipotent hemopoietic stem cell has fastidious growth requirements in vitro. Traditionally, phytohemagglutinin-stimulated leukocyte conditioned medium has been used to supply the undefined growth factors required for culture of the human multipotent hemopoietic progenitor. We describe the use of medium conditioned by the bladder carcinoma cell line, 5637, to replace PHA-LCM in CFU-GEMM cultures and show that the properties of this conditioned medium closely mimic those of PHA-LCM in two separate CFU-GEMM culture systems.

Cell Line↗

Role of quality assessment in improving red blood cell transfusion practice.

A prospective analysis of perioperative red blood cell transfusion practice in 110 patients undergoing elective primary total hip arthroplasty was conducted as a part of a quality assessment programme at the National Orthopaedic Hospital. In addition to demographic and clinical data, blood loss and perioperative transfusions were also recorded. Blood was collected for evaluation of haematocrit levels at predetermined intervals (preoperative and 6 h, 1, 2, 3, 7 days, postoperatively). Blood transfused with the patient's haematocrit of more than 30 per cent was considered inappropriate. In addition, a discharge haematocrit exceeding 36 per cent was chosen to identify overtransfusion. Eighty-four per cent were transfused a total of 191 units of homologous blood. Only 4 units were transfused between 3 patients, intraoperatively. All intraoperative transfusions were appropriate. Using the preset criteria (i.e. blood transfused with haematocrit of more than 30 per cent), 36 per cent of total units transfused were inappropriate. Using the criterion of discharge haematocrit of more than 36 per cent, 24 per cent of the patients were overtransfused. As compared to a previous retrospective analysis of blood transfusion in the same patient population which showed that inappropriate transfusion occurred in 45 per cent of the patients, the results from this study suggest a trend towards a more conservative transfusion practice. The improvement in transfusion practice may be due to the ongoing quality assurance programme and the use of transfusion guidelines.

Aged↗

The laryngeal mask airway for outpatient anesthesia.

The LMA has been commercially available since 1988, and in the United States since 1992. The device combines several advantages of endotracheal tubes and face masks and may be used in many situations where either device was previously used routinely. Its principal advantage is a clearer airway, without the morbidity associated with endotracheal intubation. Although not suitable for all patients and procedures, the LMA has become widely used in all other countries where it is available. Many of the surgical procedures for which the LMA is most suited are performed in outpatients, and we expect this device will soon become popular in carefully selected cases in this country.

Ambulatory Surgical Procedures↗