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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 1,693 records · Page 94Linked to original sources
PubMedDate not supplied

Synthesis and biological activity of a biotinylated vasopressin analog.

To study vasopressin receptor-mediated endocytosis using electronmicroscopy methods and to develop avidin affinity columns for receptor purification, we synthesized and tested the biological properties of a biotinylated vasopressin (VP) analog [1-(2-mercapto) propionic acid] 8-[lysine-N6-biotin] VP (B-MLVP). B-MLVP was prepared by coupling biotin to the epsilon amine of the lysine residue in [1-(2-mercapto) propionic acid] 8-(lysine) VP (MLVP). The structure of HPLC purified B-MLVP was confirmed by fast atom bombardment mass spectrometry. B-MLVP effectively competed for arginine vasopressin (AVP) binding sites in canine renal plasma membranes on the surface of LLC-PK1 kidney cells. Dissociation constants of 15 nM and 202 nM were calculated from the results of competition binding assays conducted with membranes and cells, respectively. B-MLVP stimulated adenylate cyclase activity and elevated cellular 3',5',cyclic-AMP (cAMP) content in a manner similar to AVP, indicating it is an agonist of VP action in renal tissue. These observations indicate that B-MLVP is an agonist of VP action and may be used to study renal VP receptors by employing avidin coupled to various reporter groups.

Adenylyl Cyclases↗
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Amphotericin B deoxycholate treatment of visceral leishmaniasis with newer modes of administration and precautions: a study of 938 cases.

Out of 938 parasitologically confirmed patients with visceral leishmaniasis treated with amphotericin B (1 mg/kg bodyweight daily infused in 2 h for 20 days), 935 were cured clinically, 933 parasitologically and 931 ultimately (no relapse within 6 months). Two parasitologically 'not cured' and 4 relapsed patients were cured with 25 infusions, and 1 with double relapse with 30 infusions. The treatment was started only when serum haemoglobin reached 5 g/dL, serum electrolyte imbalance was corrected and sodium stibogluconate-induced myocardial damage stabilized after 10 days' rest. Bronchopneumonia, cardiac failure and acute renal failure caused the death of 1 patient each. Nightblindness, angular stomatitis, neuritis, and petechial haemorrhages improved with appropriate treatment; 2 patients were given blood transfusion for post-treatment anaemia. Nausea and anorexia, and changes in serum creatinine and potassium, became normal in 2 weeks. Immediate withdrawal of the drug and restart after 10 days cured 2 patients who developed acute renal failure. Infusion-related toxicities--shivering, rigor and fever--were minimized but not eliminated by prior administration of hydrocortisone. Tuberculosis and visceral leishmaniasis were treated concurrently. Four pregnant patients were successfully treated without harmful effects on mother and child. It was concluded that the dosage of amphotericin B used was an effective and well-tolerated regimen and achieved 99% cure. Toxicity could be minimized with some precautions. All unresponsive and relapsed patients responded to more amphotericin and no resistance to the drug was seen.

Adolescent↗
PubMedDate not supplied

Recurrent giant cell reparative granuloma of hard palate: role of Tc-99m-MDP three-phase bone scan.

A 42-year-old female presented with pain in the hard palate following surgical curettage for giant cell reparative granuloma. Radiographs of the face at this time did not reveal any abnormality. The surgeons' query was to differentiate fibrosis from recurrence before considering her for recurettage. The three-phase bone scan helped in establishing the diagnosis of recurrence, which was confirmed after histological examination of the curettaged tissue.

Adult↗
PubMedDate not supplied

Gastroesophageal reflux in asthmatic children not responding to asthma medication: a scintigraphic study in 126 patients with correlation between scintigraphic and clinical findings of reflux.

Gastroesophageal reflux (GER) is frequently found in association with asthma. Successful control of GER in these patients may improve in their asthma symptoms. The present retrospective analysis was undertaken to find out the incidence of GER in asthmatic children not responding to routine antiasthmatic medications and to find out if there is a clinical correlation between the symptoms of GER and scintigraphic evidence of GER in these patients. A total of 126 children with a mean age of 2.31 years and range 6 months to 6 years were evaluated. The children were divided into two groups. Group I (n = 100) consisted of children with asthma but no clinical symptoms of GER. Group II (n = 26) consisted of those children with asthma and clinical symptoms of GER. Radionuclide scintigraphy was performed with 100-200 microCi (3.7-7.4 MBq) of Tc99m-sulphur colloid. All 33 out of 126 (26%) children had GER on scintigraphy. In Group I, only 23 (23%) had reflux while in Group II, 10 (38.5%) had reflux. In conclusion, esophageal scintiscanning can be used to detect GER in asthmatic children refractory to routine antiasthmatic medication irrespective of the presence or absence of symptoms suggestive of GER.

Anti-Asthmatic Agents↗
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Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to control transcription required for M-phase.

BACKGROUND: The 'CLB2 cluster' in Saccharomyces cerevisiae consists of approximately 33 genes whose transcription peaks in late G2/early M phase of the cell cycle. Many of these genes are required for execution of the mitotic program and then for cytokinesis. The transcription factor SFF (SWI5 factor) is thought to regulate a program of mitotic transcription in conjunction with the general transcription factor Mcm1p. The identity of SFF has yet to be determined; hence further understanding of the mechanisms that regulate entry to M phase at the transcriptional level requires characterization of SFF at the molecular level. RESULTS: We have purified the biochemical activity corresponding to SFF and identified it as the forkhead transcription factor Fkh2p. Fkh2p assembles into ternary complexes with Mcm1p on both the SWI5 and CLB2 cell-cycle-regulated upstream activating sequence (UAS) elements in vitro, and in an Mcm1 p-dependent manner in vivo. Another closely related forkhead protein, Fkh1p, is also recruited to the CLB2 promoter in vivo. We show that both FKH1 and FKH2 play essential roles in the activation of the CLB2 cluster genes during G2-M and in establishing their transcriptional periodicity. Hence, Fkh1p and Fkhp2 show the properties expected of SFF, both in vitro and in vivo. CONCLUSIONS: Forkhead transcription factors have redundant roles in the control of CLB2 cluster genes during the G2-M period of the cell cycle, in collaboration with Mcm1p.

Cell Cycle Proteins↗
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A novel pregnane derivative from Sarcostemma brevistigma.

A new pregnane derivative designated as bregenin [1] has been isolated from the dried twigs of Sarcostemma brevistigma. Chemical and spectroscopic evidence is consistent with the structure 3 beta, 14 beta, 16 alpha, 17 beta tetrahydroxypregn-5-en-20-one for bregenin.

Chemical Phenomena↗
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Caffeine-derived N-nitroso compounds. II. Synthesis and characterization of nitrosation products from caffeidine and caffeidine acid.

Caffeine on alkaline hydrolysis produces caffeidine [1-methyl-4-(methylamino)-5-(N-methylcarbamoyl)imidazole] and caffeidine acid [N-[4-(5-carboxy-1-methylimidazolyl)]-N,N'-dimethylurea]. We now report the synthesis and chemical characterization of mononitrosocaffeidine [1-methyl-4-(N-methyl-N-nitrosoamino)-5-(N-methylcarbamoyl)i midazole], dinitroso-caffeidine [1-methyl-4-(N-methyl-N-nitrosoamino)-5-(N-methyl-N-nitrosocarb amo yl) imidazole], and mononitrosamidocaffeidine [1-methyl-4-(methylamino)-5-(N-methyl-N-nitrosocarbamoyl)-Imidazole] based on spectral analysis. The characterization of nitrosated byproducts obtained during the synthesis of these compounds is also presented. Caffeidine is shown to undergo rapid nitrosation in acidic medium to form mononitrosocaffeidine (MNC), an asymmetric N-nitrosamine, and dinitrosocaffeidine (DNC), a N-nitrosamide. Although the reaction proceeds with preferential nitrosation of the amino group in caffeidine, the results also support partial involvement of a mononitrosamide intermediate in the formation of MNC and DNC through transnitrosation of the amino group. The stability data suggest that the nitroso group at the amino nitrogen in DNC influences the reactivity of amide nitroso group. The presence of a trisubstituted ureide moiety in caffeidine acid has been confirmed by NMR nuclear Overhauser effect experiments. Nitrosation of caffeidine acid under acidic conditions produced N,N'-dimethylparabanic acid (DMPA, N,N'-dimethylimidazolidinetrione) as a major product with low amounts of mononitrosocaffeidine and N,N'-dimethyl-N-nitrosourea, whereas nitrosation with NOBF4/pyridine in aprotic medium gave rise to an anhydride, 1,4-dimethyl-4,5-dihydro-5,7-dioxo-1H,7H-imidazo[4,5-d][1,3]oxazine. The nitrosation of methyl ester of caffeidine acid resulted in the formation of a N-nitrosourea derivative, N-[4-(5-carboxy-1-methylimidazolyl)]-N'-nitroso-N,N'-dimethylurea. (ABSTRACT TRUNCATED AT 250 WORDS)

Caffeine↗
PubMedDate not supplied

Correlation between LUTS (AUA-SS) and erectile dysfunction (SHIM) in an age-matched racially diverse male population: data from the Prostate Cancer Awareness Week (PCAW).

The relationship between lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia and sexual health in men participating in a national multicenter screening program was studied. A total of 12 679 men were screened for prostate cancer in the year 2003. Of these, 6641 men had completed both the American Urological Association Symptom Score (AUA-SS) and the Sexual Health Inventory for Men (SHIM) questionnaires. We assessed the apparent effect of comorbidities (ischemic heart disease, hypertension, hypercholesteremia and diabetes), smoking habits and testosterone level on the overall sexual health. Age and race were also assessed as factors affecting the SHIM score. We used a general linear multivariable regression analysis to express the effect of these variables on the sexual health in these men adjusting for the apparent effect of LUTS. The mean and median age of the population was 58.4 +/- 9.8 and 58 y, respectively. The median AUA-SS was 4/25 (mean=5.7 +/- 5.3) and SHIM score was 19/25 (mean=16.3 +/- 5.9). Of the men, 4948 (75%) were Caucasian and 1154 (17%) were from African-American racial origin. A high AUA-SS appears to have a negative effect on the overall sexual health (P<0.05) after adjusting for all other confounding factors. As expected, age showed a significant inverse correlation with SHIM score (P<0.05). Caucasian men on average appear to have a significantly higher SHIM score by 6.5 points when compared to African-American men after adjusting for age, comorbidities, smoking habits, and AUA-SS (P<0.05). However, with increasing age, the difference in SHIM score diminishes between the two groups. Further, smoking and comorbidities were strong predictors of poor sexual health performance. Interestingly, hypogonadism (testosterone <300 ng/dl) was not a significant risk factor (P=0.104) when adjusting for all other variables. Nonetheless, in a univariate analysis, testosterone levels significantly correlated with reported SHIM scores (P<0.05). The overall sexual health in aging men is substantially affected not only by age, but by the severity of their urinary symptoms after adjusting for the most common known risk factors, suggesting perhaps a common underlying pathophysiology. Moreover, race appears to constitute another neglected potential risk factor, which should be investigated further in future studies.

Adult↗
PubMedDate not supplied

Single dilution ELISAs using soluble piroplasm, cellular schizont and soluble schizont antigens for the detection of antibodies against Theileria annulata.

Single dilution ELISAs were standardised for the determination of antibody titres against Theileria annulata using three antigens namely soluble piroplasm, cellular schizont or soluble schizont antigens. Antibody titres of 20 cattle serum samples of known identity were determined by multi-dilution ELISA using the three antigens. The ratio of the optical density (OD) of known positive and known negative sera at different serum dilutions were calculated and termed as positive/negative (P/N) ratios. Coefficients of correlation (r) were calculated between the P/N ratios at different dilutions of known sera and their log10 antibody titres by multi-dilution ELISA. The value of "r" was the highest at the dilution of 1:400. From the log10 antibody titres of known sera and their P/N ratios at the dilution of 1:400, regression equations (Y = a + bX, where Y = predicted log10 titre, X = the P/N ratio at 1:400 dilution) were calculated separately for the three antigens. Thus, the equations Y = 1.63 + 1.35X for soluble piroplasm, Y = 2.67 + 0.547X for cellular schizont and Y = 1.817 + 0.663X for soluble schizont antigens were derived. Test sera were diluted to 1:400 and their OD were read in duplicate wells and converted to P/N ratios. The antibody titres were predicted from the P/N ratios using the above mentioned regression equations. Twenty randomly selected sera tested by single and multidilution ELISAs showed non-significant differences (P < 0.01) between antibody titres. Antibody titres of 90 unknown field sera of cattle were determined by single dilution ELISA. The piroplasm antigen detected higher antibody titres followed by cellular schizont and soluble schizont antigens. The study revealed that a single dilution ELISA could be successfully used for field epidemiological studies of tropical theileriosis.

Animals↗
PubMedDate not supplied

A new chromone from Cassia nodosa.

A new chromone named as 5,4'-dihydroxy-7-methyl 3-benzyl chromone (1) along with three known flavonoid compounds as unsubstituted flavone, kaempferol-3-o-rhamnoside and quercetin-3-o-arabinoside have been isolated from the leaves of Cassia nodosa. Their structures have been established by means of chemical and spectral evidences (IR, UV, 1H-NMR, 13C-NMR and mass spectra).

Cassia↗
PubMedDate not supplied

Formulation, characterization, and in vitro release of glyburide from proliposomal beads.

The objective of our study was to formulate and evaluate proliposomes in the form of enteric-coated beads using glyburide as a model drug. The beads were enteric coated with Eudragit L-100 by a fluidized bed coating process using triethyl citrate as plasticizer. Content uniformity of glyburide was estimated using HPLC analysis of beads dissolved in methanol. These proliposomal beads formed liposomes on disintegration in phosphate buffered saline (pH 7.4), which was confirmed by transmission electron microscopy. The dissolution study of enteric-coated beads exhibited enhanced dissolution compared with pure drug and a marketed product. Liposomes can be successfully prepared for oral administration in the form of enteric-coated beads that may offer a stable system to produce liposomes for oral administration.

Chemistry, Pharmaceutical↗
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LNA (locked nucleic acid) and the diastereoisomeric alpha-L-LNA: conformational tuning and high-affinity recognition of DNA/RNA targets.

The remarkable binding properties of LNA (Locked Nucleic Acid) and alpha-L-LNA (the alpha-L-ribo configured diastereoisomer of LNA) are summarized, and hybridization results for LNA/2'-O-Me-RNA chimera and LNAs with a "dangling" nucleotide are introduced. In addition, results from NMR investigations on the furanose conformations of the individual nucleotide monomers in different duplexes are presented. All these data are discussed with focus on the importance of conformational steering of unmodified nucleotides in partly modified LNA and alpha-L-LNA sequences in relation to the unprecedented binding properties of LNA and alpha-L-LNA.

DNA↗
PubMedDate not supplied

Effect of antibiotics on Oxalobacter formigenes colonization of human gastrointestinal tract.

BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in the human gastrointestinal tract that degrades oxalate and reduces its availability for absorption. This bacterium is assumed to be antibiotic sensitive, and repeated antibiotic therapies could eradicate it. The aim of the present study was to determine the differences in the colonization by O. formigenes of individuals who had been on antibiotics for at least 5 days at the time of sample collection and individuals who had not taken antibiotics for at least 3 months. PATIENTS AND METHODS: Stool samples were collected from 80 individuals without stone disease (35 with and 45 without antibiotic consumption) and 100 patients with stone disease (20 with and 80 without antibiotic consumption). Oxalobacter formigenes was detected by a polymerase chain reaction-based method, and the presence/absence of O. formigenes was correlated with urinary oxalate concentrations. RESULTS: Lower percentages of individuals without stone disease and with stone disease who were consuming antibiotics had O. formigenes colonization than individuals without antibiotic consumption. Urinary oxalate concentrations were higher in the individuals without O. formigenes than in colonized individuals. CONCLUSION: Our observations confirm a direct association between antibiotic consumption and absence of O. formigenes. Absence of intestinal O. formigenes could represent a pathogenic factor in calcium oxalate urolithiasis when antibiotics are prescribed generously.

Absorption↗
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Case report: managing fractures in non-compliant alcoholic patients--a challenging task.

AIMS: To investigate whether there are extractable conclusions for limb fracture management in dependent alcoholics. METHODS: We discuss four cases of dependent alcoholics who presented in our department over a 12-month period, and who developed significant complications owing to non-compliance with treatment. RESULTS: Initial treatment, although appropriate, failed because of non-compliance. This led to further admissions, wound infections and surgery to enable cure. CONCLUSIONS: Our case reports indicate that for upper limb fractures of the middle third of the humerus, non-operative treatment or internal fixation with out-patient detoxification is appropriate. Lower limb fractures, on the other hand, should be dealt with by external fixation and in-patient detoxification. It is imperative that the alcohol dependence is addressed if we are to decrease non-compliance.

Adult↗
PubMedDate not supplied

Effect of lumbar orthotics on trunk muscle strength.

Weakening of the trunk muscles is thought to be one disadvantage of prolonged lumbar orthotic use. This study examines weakness of the trunk flexor and extensor muscles in patients who are wearing lumbar orthotics for extended periods. Strength of the trunk flexor and trunk extensor muscles was tested in 24 individuals, using the Kinetic computer. Both concentric and eccentric forces were recorded. Four groups of patients were studied. Group 1 (n = 6) consisted of patients with low back pain who had used a lumbar orthotic for a prolonged period of time. Group 2 (n = 6) consisted of hospital employees with no history of low back pain, who wore lumbar orthotics prophylactically, for back protection. Group 1C (n = 6) consisted of healthy controls, with no history of either back pain or lumbar orthotic use, who were individually age- and gender-matched to each patient in Group 1. Group 2C (n = 6) consisted of healthy controls matched in the same fashion to each patient in Group 2. After consultation with a statistician, statistical analysis was performed using the Wilcoxon's test. Nonparametric statistics were chosen because of the lack of evidence of a normal distribution of the parameters being studied. This analysis revealed significant weakness in concentric flexion (P = 0.0464), concentric extension (P = 0.0277), and eccentric extension (P = 0.0464) in Group 1 compared with matched controls in Group 1C. The only significant weakness compared with controls in Group 2 was in eccentric flexion (P = 0.0277). Trends were toward weakness in the orthotic users for the other motions studied, with a P value of less than 0.1 for eccentric extension. Prolonged use of lumbar orthotics may be associated with trunk muscle weakness in the population studied. Prescribers should continue to limit duration of use when possible and to consider strengthening exercises when prolonged use is anticipated.

Adult↗
PubMedDate not supplied

Deep vein thrombosis after lower limb amputation.

OBJECTIVE: The purpose of this study is to prospectively document the incidence of deep vein thrombosis (DVT) in the residual limb after a below-knee amputation. DESIGN: Eight of 13 male patients, admitted to the acute rehabilitation floor after a below-knee amputation, were included in the study. Patients already receiving anticoagulants were excluded. An investigator questioned the patient regarding the patient's risk factors for DVT and history of DVT and pulmonary embolus. A coagulation profile was obtained for all patients. A Doppler ultrasound was completed on the residual limb 2 wk after amputation, and if negative, it was repeated 2 wk later. Patients found to have a DVT were treated appropriately. The incidence of DVT was calculated by a point estimate, and a 95% confidence interval was calculated using simple large sample methods. RESULTS: Four of the eight patients had ultrasound evidence of DVT in the thigh. Two of the four patients had signs or symptoms of a DVT. There were a comparable number of risk factors for DVT in both groups. Laboratory values were not statistically significant in predicting the occurrence of DVT, probably because of the limited number of subjects. CONCLUSIONS: The present study supports the assumption that the diagnosis of lower limb DVT is frequently associated with lower limb amputation. However, a larger sample may be necessary to conclude that a routine screening ultrasound of the lower limbs is indicated after a below-knee amputation.

Adult↗