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Biomedical subjects

B Paul

Publications and source records attributed to B Paul.

At least 37 records · Page 2Linked to original sources

Purification and characterization of a polyphenol oxidase from the seeds of field bean (Dolichos lablab).

The polyphenol oxidase from field bean (Dolichos lablab) seeds has been purified to apparent homogeneity by a combination of ammonium sulfate precipitation, DEAE-Sephacel chromatography, phenyl agarose chromatography, and Sephadex G-200 gel filtration. The purified enzyme has a molecular weight of 120 +/- 3 kDa and is a tetramer of 30 +/- 1.5 kDa. Native polyacrylamide gel electrophoresis of the purified enzyme revealed the presence of a single isoform with an observed pH optimum of 4.0. 4-Methyl catechol is the best substrate, followed by catechol, and L-3,4-dihydroxyphenylalanine, all of which exhibited a phenomenon of inhibition by excess substrate. No activity was detected toward chlorogenic acid, catechin, caffeic acid, gallic acid, and monophenols. Tropolone, both a substrate analogue and metal chelator, proved to be the most effective competitive inhibitor with an apparent K(i) of 5.8 x 10(-)(7) M. Ascorbic acid, metabisulfite, and cysteine were also competitive inhibitors.

Amino Acid Sequence↗

Role of losartan therapy in the management of diabetic hypertension.

The management of diabetic hypertension requires meticulous selection of agents in the antihypertension armamentorium. There may be several associated factors to be considered while treating a hypertensive diabetic. These include hyperglycemia, dyslipidemia, proteinuria, left ventricular hypertrophy and heart failure to name a few. Losartan is the first of a new class of agents in the list of antihypertensive drugs. By its selective angiotension II receptor (subtype AT1) blocking action it is postulated to bring about a more complete inhibition of the renin-angiotensin system. Thus, it might produce all the benefits of angiotensin converting enzyme (ACE) inhibitor therapy with the freedom from cough so commonly seen with the use of ACE inhibitors. This review attempts to analyze the possible benefits of losartan therapy in diabetes.

Diabetes Complications↗

Occurrence of resveratrol and pterostilbene in age-old darakchasava, an ayurvedic medicine from India.

'Darakchasava' is a well known Indian herbal preparation of which the main ingredient is Vitis vinifera L. This 'ayurvedic' medicine is prescribed as a cardiotonic and also given for other disorders. HPLC analysis of this age old formulation revealed the presence of polyphenols like resveratrol and pterostilbene. These phenolic compounds are now known as antioxidants, cancer chemopreventive agents, and also known to reduce mortality from coronary heart disease by increasing high density lipoproteins like cholesterol and inhibiting platelet aggregation (Soleas, J.S., Diamandis, E.P., Goldberg, D.M., 1997. Resveratrol: a molecule whose time has come? and gone? Clin. Biochem. 30 (2), 91-113). The study of darakchasava becomes interesting in the light of these findings. A brief introduction of this medicinal preparation, its formulation, its analysis by HPLC, and some of its properties are discussed in this article.

Antineoplastic Agents, Phytogenic↗

Pythium periplocum, an aggressive mycoparasite of Botrytis cinerea causing the gray mould disease of grape-vine.

Pythium periplocum Dreschler has been found to be an aggressive mycoparasite of Botrytis cinerea, the causal agent of the gray mould disease of the grape-vine. When grown together, the former enters the latter's mycelium, branches freely within, coagulates its cytoplasm and finally tears its hyphae apart, bringing about widespread destruction of the grape-vine pathogen. Extensive coiling around the host, as reported in the case of other mycoparasites belonging to the genus Pythium, has not been observed here. The infected mycelium of B. cinerea fails to infect the grape-vine and does not induce the characteristic gray mould symptoms. Since P. periplocum is not a grape-vine parasite, it could be useful for the biological control of B. cinerea. A brief account of this mycoparasitism is discussed in this article.

Botrytis↗

Pythium ornacarpum: a new species with ornamented oogonia isolated from soil in france.

Pythium ornacarpum sp. nov. was isolated from a soil sample taken from Genlis in the Burgundy region of France. This species is unique because of its ornamented oogonia which are completely surrounded by antheridial filaments. The fungus is closely related to Pythium echinulatum Matthews. Morphological and reproductive aspects of this species as well as a study by PCR of the sequence of the internal transcribed spacer (ITS1) of the nuclear ribosomal gene and its comparison with related species are described here. The nucleotide sequence of the ITS1 region flaking the 5.8S rRNA of this species and other related species are also given here.

Base Sequence↗

Toxicity of a particulate formulation for the intraperitoneal application of mitoxantrone.

Mitoxantrone (MXN) has demonstrated therapeutic efficacy in the intraperitoneal treatment of malignancies. However, severe local toxicity is dose limiting. Therefore, a particulate formulation of MXN, the drug incorporated in albumin microspheres, was evaluated concerning tolerability. Survival rates as well as alterations in body weight, food intake, water intake, urine volume, urine specific gravity, urine protein content, and complete blood count were observed following single or multiple intraperitoneal injections of MXN solution, dispersions containing MXN-loaded microspheres or unloaded microspheres, and the injection vehicle to female and male Sprague-Dawley rats. Applied MXN dosage was equivalent to 30 mg/m2 body surface area. Unloaded microspheres were well tolerated without signs of toxicity. Application of MXN solution or MXN-loaded microspheres resulted in similar survival rates (56% 9 weeks after single injection) and in a comparable bone marrow toxicity (mainly leucopenia). Body weight, food and water intake as well as urine volume were decreased following application of MXN solution, whereas a progressive gain in weight and no remarkable alterations in nutrition and urine excretion were noted after administration of MXN-loaded and unloaded microspheres, or of the injection vehicle. In conclusion, intraperitoneal injection of MXN incorporated in albumin microspheres exhibits in part less toxicity than conventional treatment.

Animals↗

Pythium prolatum isolated from soil in the Burgundy region: a new record for Europe.

Pythium prolatum Hendrix and Campbell has been isolated from a soil sample taken in the Burgundy region in France. The fungus is easily recognisable by its heavily ornamented oogonia with conical to mammiform spines, elongated sporangia, and its diclinous antheridia forming or originating from a tangled mass of hyphae. Descriptions of the morphological and reproductive aspects of Pythium prolatum, the polymerase chain reaction of the internal transcribed spacer (ITS1) of the ribosomal nuclear DNA as well as the nucleotide sequences of ITS1 coding for 5.8S rRNA are given.

Base Sequence↗

Evaluation of mitoxantrone-loaded albumin microspheres following intraperitoneal administration to rats.

Mitoxantrone has demonstrated therapeutic efficacy in the regional treatment of intraperitoneal malignancies. However, severe local toxicity was dose limiting. Consequently, a new injectable sustained delivery formulation of mitoxantrone has been developed: the drug was incorporated (8.2 w/w%) in highly hydrophilic albumin microspheres. In vitro drug release profile was modified by matrix crosslinking extent. The extractable amount of residual crosslinking agent (glutaraldehyde) in the microspheres was lower than 6 ppm. Mitoxantrone concentration in peritoneal fluid and plasma was determined up to 72 h after intraperitoneal administration of 30, 60 and 120 mg mitoxantrone per m2 body surface area as solution and in the form of a dispersion containing mitoxantrone-loaded microspheres to rats. Data analysis revealed sustained release of mitoxantrone from microspheres into peritoneal fluid in all dosage groups. The initial high drug levels in peritoneal fluid and plasma observed after application of mitoxantrone in the solution form were prevented by administration of the drug incorporated in microspheres. However, tumoricidal drug levels in peritoneal fluid were maintained over a comparable time span. In addition, preliminary toxicity data suggest a superior local tolerability of mitoxantrone-loaded microspheres. The dose of intraperitoneally administered mitoxantrone might be increased from 30 to 60 mg per m2 body surface area using the slow release formulation. In conclusion, the described microsphere drug delivery system for mitoxantrone might overcome dose-limiting drug toxicity.

Albumins↗

Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania.

OBJECTIVE: Case series and follow-up studies suggest that clozapine may have mood-stabilizing properties in addition to antipsychotic action in patients with schizoaffective disorder, bipolar type, and bipolar I disorder, but the generalizability of these findings is limited. This article describes a randomized, open study of clozapine add-on therapy versus treatment as usual for patients with treatment-resistant illness and a history of mania. METHOD: Thirty-eight patients meeting the DSM-IV criteria for schizoaffective or bipolar disorder that was deemed treatment-resistant were randomly assigned to clozapine add-on treatment (N = 19) or treatment as usual (no clozapine) (N = 19) and followed up for 1 year. Patients received monthly ratings on the Brief Psychiatric Rating Scale, Clinical Global Impression scale, Bech-Rafaelsen Mania Scale, Hamilton Depression Rating Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Abnormal Involuntary Movement Scale, and a 40-item side effect checklist. Differences between treatment groups were assessed according to a pattern-mix random-regression model. An additional analysis compared group differences in rating scale scores against relative time in the study. RESULTS: Significant between-group differences were found in scores on all rating scales except the Hamilton depression scale. Total medication use over 1 year significantly decreased in the clozapine group. No significant differences between groups in somatic complaints were noted. The subjects with nonpsychotic bipolar I disorder who received clozapine showed a degree of improvement similar to that of the entire clozapine-treated group. Clozapine dose was significantly higher for the patients with schizoaffective illness than for those with bipolar disorder. CONCLUSIONS: The results of this study support clozapine's independent mood-stabilizing property. They demonstrate that clozapine use was associated with significant clinical improvement relative to treatment as usual.

Adult↗

A new species of Pythium isolated from the Burgundy region in France.

Pythium nodosum sp. nov. has been isolated from a soil sample taken in the Burgundy region in France. The fungus has spherical to variously shaped proliferating sporangia, smooth-walled oogonia which are crowded with different antheridial branches making a complicated knot around the former, and aplerotic oospores. Morphological and reproductive aspects of Pythium nodosum as well as the PCR of the internal transcribed spacer (ITS1) of the ribosomal nuclear DNA coupled with restriction fragment length polymorphism analysis are described here. The nucleotide sequences of ITS1 encoding 5.8S rRNA is also given.

Base Sequence↗

Monitoring efficacy of commonly used antimalarials by a 14-day in-vivo test in a new settler's camp in endemic zone at Cox's Bazar.

The study was done in a new settler's camp "Barachara" under Sadar thana of Cox's Bazar district. It has a total population of 784 of all age groups, registered in the middle of the study period. A prospective evaluation of all cases of fever were done over 12 months, to see the pattern of febrile illness among the population and to compare the therapeutic efficacy of two alternative drug regimens for uncomplicated falciparum malaria (UM). Blood for malarial parasite (MP) was done in all cases of fever and was treated in line with the new clinical case definitions and treatment guidelines for malaria in Bangladesh. Slide positive UM cases were subjected to a "14-day in-vivo test" for therapeutic efficacy testing of antimalarial agents. The two drug regimens were randomised by lottery--a) 3 days oral chloroquine plus single dose sulphadoxin/pyrimethamine (CQ + SP) and, b) 3 days oral quinine plus single dose sulphadoxin/pyrimethamine (Q3 + SP). Drug administration was supervised by the field assistant and was followed up on days 3, 7 and 14 for blood slide examinations and clinical assessment. Sensitive response was observed in 79% of the cases in the CQ + SP group and 84% in the Q3 + SP group. Early treatment failure (persistently febrile and parasitaemic on days 3 or 7) was observed in 16% in the CQ + SP group and 9% in the Q3 + SP group. Both the evaluated drug regimens had less than 20% failures and can be used as alternative first line agents and Q3 + SP regimens can also be used as the second line agents for treatment failure (to chloroquine and/or SP) UM cases in the study area.

Adolescent↗

To compare and contrast the various evaluation scoring systems after anterior cruciate ligament reconstruction.

In a prospective study we evaluated with eight established scoring systems 56 patients who received a Leeds-Keio ligament as an anterior cruciate ligament replacement. The systems were compared based upon their total results, as well as their subjective, objective and functional criteria. It was found that the diversity of both the results and criteria within the systems made valid comparisons impossible. From this investigation it was concluded that the use of an internationally standardized evaluation system would provide the best possibility for comparison of surgical results. As a result, we recommend the IKDC Score system together with a visual analogue scale to evaluate subjective knee complaints.

Adult↗

Normative auditory brainstem response data for bone conduction in the dog.

Auditory brainstem response (ABR) is a valuable tool for the diagnosis of hearing disorders in dogs, but is hampered by the lack of published normative data. The aim of the present study was to obtain normative data for bone conduction, without masking, under clearly defined conditions. Subjects comprised 20 Dalmatians and 20 Jack Russell terriers. Two methods were investigated: holding the bone vibrator against the head by hand or by applying a 500 g weight. The results revealed no difference in hearing threshold between the two breeds or for the two methods of applying the bone vibrator to the head. The mean hearing threshold was close to 0 decibels re normal hearing level (dB nHL), which is the biological norm for humans. Hence, bone conduction thresholds can be used for confirmation of conductive hearing impairment in the dog, in the same way as in humans.

Animals↗

Direct Coombs test-negative autoimmune hemolytic anemia and low-affinity IgG class antibodies.

Autoimmune hemolytic anemia, in which the direct antiglobulin test (DAT) is negative or weakly positive, may be due to low-affinity autoantibodies. We describe two such cases. An 8-year-old male presented with weight loss, jaundice, a hemoglobin of 33 g/L, reticulocytes of 306 x 10(9)/L, and haptoglobin of < 0.1 g/L. The DAT was negative. After washing the red blood cells (RBCs) with saline at 4 degrees C, the DAT was positive for IgG and an eluate contained an IgG3 autoantibody, thus confirming a diagnosis of autoimmune hemolytic anemia (AIHA). Red cell transfusions and corticosteroids were given with eventual complete recovery. A 73-year-old male had a hemoglobin of 89 g/L and haptoglobin of < 0.1 g/L. The DAT was initially negative but was positive for IgG using cold-washed (4 degrees C) RBCs; it was also positive with unwashed cells in the DiaMed system and an eluate contained IgG1 autoantibody. AIHA was therefore confirmed and prednisolone started but continued hemolysis necessitated splenectomy before full recovery occurred. Although RBCs may be strongly sensitized with low-affinity autoantibodies in vivo, the IgG is easily removed when RBCs are washed at room temperature for a DAT. The DiaMed system that uses unwashed RBCs overcomes this problem, but cold washing the RBCs at 4 degrees C must be used when preparing eluates.

Journal Article↗

Biological properties of fluoroglutamate-containing analogs of folates and methotrexate with altered capacities to form poly (gamma-glutamate) metabolites.

Fluoroglutamate-containing analogs of folates and methotrexate (MTX) with altered capacities for poly (gamma-glutamate) metabolism were synthesized to probe the biological roles of polyglutamates. Compared to folic acid, DL-e,t-gamma-fluorofolic acid, a compound that is a poor substrate for polyglutamylation, was approximately 25-fold less potent in promoting growth of folate-depleted H35 rat hepatoma cells. DL-beta,beta-Difluorofolic acid, a compound that forms diglutamates more readily than does folic acid, was at least equivalent to folic acid in potency. Leucovorin (LV), a reduced folate, was 30-fold more potent than folic acid in promoting growth, whereas the analogous form of DL-e,t-gamma-fluorofolate, DL-e,t-gamma-fluoroleucovorin (DL-e,t-gamma-FLV) was only 4-fold more potent than folic acid. Both LV and DL-e,t-gamma-FLV protected or "rescued" cells from the growth inhibitory effects of MTX; however a 37- to 46-fold higher concentration of the fluoro analog was required. Folic acid, DL-e,t-gamma-fluorofolic acid, LV, and DL-e,t-gamma-FLV each potentiated the growth inhibitory effect of 5-fluoro-2'-deoxyuridine on CCRF-CEM human leukemia cells; higher concentrations of fluorinated analogs again were required. Stereochemically pure L-t-gamma-fluoromethotrexate (L-t-gamma-FMTX), a poor substrate for polyglutamylation, was evaluated as a cell growth inhibitor. In continuous exposure, L-t-gamma-FMTX), was 7-fold less potent than MTX as an inhibitor of CCRF-CEM growth. Results with these fluorinated folate and MTX analogs offer insight into the importance of polyglutamate metabolism to these biological and pharmacological effects.

Animals↗

Analysis of genetic instability during mammary tumor progression using a novel selection-based assay for in vivo mutations in a bacteriophage lambda transgene target.

Genetic instability is thought to be responsible for the numerous genotypic changes that occur during neoplastic transformation and metastatic progression. To explore the role of genetic instability at the level of point mutations during mammary tumor development and malignant progression, we combined transgenic mouse models of mutagenesis detection and oncogenesis. Bitransgenic mice were generated that carried both a bacteriophage lambda transgene to assay mutagenesis and a polyomavirus middle T oncogene, mammary gland-targeted expression of which led to metastatic mammary adenocarcinomas. We developed a novel assay for the detection of mutations in the lambda transgene that selects for phage containing forward mutations only in the lambda cII gene, using an hfl- bacterial host. In addition to the relative ease of direct selection, the sensitivity of this assay for both spontaneous and chemically induced mutations was comparable to the widely used mutational target gene, lambda lacI, making the cII assay an attractive alternative for mutant phage recovery for any lambda-based mouse mutagenesis assay system. The frequencies of lambda cII- mutants were not significantly different in normal mammary epithelium, primary mammary adenocarcinomas, and pulmonary metastases. The cII mutational spectra in these tissues consisted mostly of G/C-->A/T transitions, a large fraction of which occurred at CpG dinucleotides. These data suggest that, in this middle T oncogene model of mammary tumor progression, a significant increase in mutagenesis is not required for tumor development or for metastatic progression.

Animals↗