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Biomedical subjects

Ashok Kumar

Publications and source records attributed to Ashok Kumar.

At least 127 records · Page 7Linked to original sources
PubMed2005

Evaluation of radioprotective effects of Rajgira (Amaranthus paniculatus) extract in Swiss albino mice.

The radioprotective efficacy of aqueous extract of Rajgira (Amaranthus paniculatus) leaves against whole body gamma radiation was studied in Swiss albino mice. The oral administration of Rajgira extract at 800 mg/kg body weight/day for 15 consecutive days before whole body exposure to radiation was found to be effective with the LD50/30 values of 6.33 and 8.62 Gy for irradiation alone and Rajgira+irradiation group, respectively, giving a dose reduction factor of 1.36. This effect of Rajgira accompanied the increased endogenous spleen colonies and the spleen weight without any side effect or toxicity, as well as the modulation of the radiation-induced decrease of reduced glutathione and the radiation-induced increase in lipid peroxidation assessed in the liver and the blood.

Administration, Oral↗
PubMed2005

Maternal thyroid hormonal status in preeclampsia.

BACKGROUND: The physiological changes in the thyroid gland during pregnancy are well understood but only a few reports provide information about thyroid function in complicated pregnancies. AIMS: The present study evaluates thyroid hormonal levels in cases of preeclampsia in the third trimester of pregnancy. SETTINGS & DESIGN: A case-control study was conducted in the antenatal clinic of a public hospital of Delhi. METHOD & MATERIALS: Thyroid hormones, namely triiodothyronine (Free T3), thyroxine (Free T4) and thyroid stimulating hormone (TSH) were evaluated at the time of diagnosis of preeclampsia in 82 pregnant women and equal number of matched controls. STATISTICAL ANALYSIS: The demographic data and hormone levels were analyzed using students' t test, Mann-Whitney test and chi-square test. Pearson two-tailed analysis was used for correlation. RESULTS: Mean TSH levels were significantly higher in preeclamptic group as compared to controls (p< 0.001). However, mean values of thyroid hormones were in the normal range. Approximately 40% preeclamptic women had TSH titres > 5 mIU/ml in the study group as compared to 12.2% in the controls. Approximately 76.7% of 43 pregnant women with abnormal TSH titres and 40% of 121 pregnant women with normal TSH titres belonged to the study group (p< 0.001). The odd ratio corresponding to TSH titres > 5 mIU/ml in preeclamptic women was 4.85 (95% CI 2.19-10.74). CONCLUSIONS: Mean serum TSH levels were significantly increased without concomitant changes in free T3 and T4, in preeclampsia compared to normal pregnancy. Abnormal TSH titres might be associated with a risk for occurrence of preeclampsia.

Adult↗
PubMed2005

Isolation, phage typing and antibiogram of Salmonella from man and animals in northeastern India.

BACKGROUND AND OBJECTIVE: Salmonella is an important zoonotic pathogen and its prevalence in the animals acts as a continuous threat to man. The present study was carried out to report the isolation along with the serotypes, phage types and antibiogram pattern of Salmonella among man, livestock and poultry in the northeastern India. METHODS: A total of 654 samples from diarrhoeic livestock and humans were processed for the isolation of Salmonella. All the isolates were subjected to antibiogram studies against 15 antimicrobials. Representative isolates of S. Typhimurium and S. Enteritidis were phage typed. RESULTS: Ninety five isolates of Salmonella enterica belonging to 5 serotypes- S. Typhimurium, S. Enteritidis, S. Gallinarum, S. Paratyphi B and S. Bareilly were obtained with an overall prevalence rate of 14.40 per cent. S. Typhimurium isolates were distributed among four phages- DT003, DT004, DT096 and DT193 and all the S. Enteritidis isolates belonged to a single phage type, PT13a/7. Interspecies sharing of the phages was observed. Norfloxacin, enrofloxacin, gentamycin and ciprofloxacin were most effective, whereas, doxycycline, ampicillin, amoxycillin and tetracycline were relatively less effective. INTERPRETATION AND CONCLUSION: Our findings showed that three of the five serovars as well as some of the phage types of these serovars were shared by animals and humans indicating the zoonotic potential of the organism. Thus, it is imperative that salmonellosis control measures adopted for humans should give adequate importance to its control in the animals particularly their products.

Animals↗
PubMed2004

Quantum dot-antibody and aptamer conjugates shift fluorescence upon binding bacteria.

CdSe/ZnS quantum dots (QDs) exhibited fluorescence emission blue shifts when conjugated to antibodies or DNA aptamers that are bound to bacteria. The intensity of the shifted emission peak increased with the number of bound bacteria. Curiously, the emission was consistently shifted to approximately 440-460 nm, which is distinctly different from the major component of the natural fluorescence spectrum of these QDs. This minor emission peak can grow upon conjugation to antibodies or aptamers and subsequent binding to bacterial cell surfaces. We hypothesize that the wavelength shift is due to changes in the chemical environment of the QD conjugates when they encounter the bacterial surface and may be due to physical deformation of the QD that changes the quantum confinement state. Regardless of the mechanism, these remarkable emission wavelength shifts of greater than 140 nm in some cases strongly suggest new applications for QD-receptor conjugates.

Antigen-Antibody Complex↗
PubMed2004

Lactose biosensor based on Langmuir-Blodgett films of poly(3-hexyl thiophene).

An amperometric lactose biosensor was developed by immobilizing lactase (EC 3.2.1.23) and galactose oxidase (GaO) (EC 1.1.3.9) in Langmuir-Blodgett (LB) films of poly(3-hexyl thiophene) (P3HT)/stearic acid (SA) for estimation of lactose in milk and its products to prevent "lactose intolerance". The enzyme immobilized LB film was used as working electrode and platinum as reference electrode. The enzyme electrodes show a linearity 1-6 g/dL of lactose and have a shelf life more than 120 days. The reusability of electrode was found ten times with 3% loss in current response. The enzyme electrode was characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and kinetic parameters such as pH, temperature and stability. The working electrode may be used for the estimation of lactose/galactose in food and biological fluids.

Animals↗
PubMed2004

Extracellular calcium induces COX-2 in osteoblasts via a PKA pathway.

We have shown that extracellular calcium [Ca(+2)](e) induces cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) production via an ERK signaling pathway in osteoblasts. In this study, we examined the roles of protein kinase C (PKC) and A (PKA) signaling pathways in the [Ca(+2)](e) induction of COX-2 in primary calvarial osteoblasts from mice transgenic for -371 bp of the COX-2 promoter fused to a luciferase reporter. Neither PKC specific inhibitors nor downregulation of the PKC pathway by phorbol myristate acetate (PMA) affected the [Ca(+2)](e) stimulation of COX-2 mRNA or promoter activity. In contrast, PKA inhibitors, used at doses that inhibited forskolin-stimulated luciferase activity by 90%, reduced [Ca(+2)](e)-stimulated COX-2 mRNA expression and promoter activity by 80-90%. [Ca(+2)](e) also stimulated a 2- to 3-fold increase in cAMP production. Hence, the [Ca(+2)](e) induction of COX-2 mRNA expression and promoter activity was independent of the PKC pathway and dependent on the PKA signaling pathway.

Animals↗
PubMed2004

Integrated isolation of antibody fragments from microbial cell culture fluids using supermacroporous cryogels.

The present paper describes a chromatographic capture/purification step for the recovery of proteins directly from undiluted and unclarified cell culture broths using supermacroporous dimethylacrylamide (DMAA) cryogel. The interconnected character and the size (10-100 microm) of the pores of the adsorbent make it possible to process whole cell fermentation broths without blocking the column. Cu2+-iminodiacetic acid (IDA) DMAA cryogel has been used for the isolation and purification of excreted (His)6-tagged single chain (sc) Fv antibody fragments, (His)6-scFv, from E. coli cell culture. Bound protein was recovered with 0.2 M imidazole or with 20 mM EDTA and was practically cell-free. Chromatographic capture using Cu2+-IDA cryogel column was performed at flow rates of 300 and 600 cm/h, respectively and resulted in 84-96% recovery of (His)6-scFv fragments with a purification factor of 13-15. The DMAA cryogel adsorbent is mechanically stable, can withstand harsh cleaning-in-place procedure and is relatively inexpensive. Chromatographic isolation of proteins using cryogels allows efficient removal of cells and can be operated at a flow rate as high as 600 cm/h. This novel technique has proven to be a scalable process, does not require special equipment and can be a good alternative to expanded bed adsorption and other integrated isolation techniques.

Acrylamide↗
PubMed2004

Evidences showing ultraviolet-B radiation-induced damage of DNA in cyanobacteria and its detection by PCR assay.

Impact of ultraviolet-B radiation in causing the damages to the DNA of the cyanobacterium, Anabaena strain BT2 has been investigated. Exposure of genomic DNA (in vitro) to UV-B radiation for 1 h did not cause any shift in the absorption peak (lambda(max)) but more than 30% increase in absorbance was noticed in comparison to untreated control DNA (no exposure to UV-B). This increase in absorbance in a way may be comparable to typical hypochromic effect but there was no decrease in absorbance following transfer of UV-B-treated DNA to fluorescent light or in the dark. That the damaging effect of UV-B radiation on native structure of DNA is indeed real was also evident from the PCR-based assay such as RAPD, rDNA amplification, and ARDRA. Template activity of UV-B-treated genomic DNA was drastically inhibited, there was no amplification in RAPD assay after prior exposure of DNA to UV-B for 60 min. Only one band of approximately 400 bp was observed even after 60 min of exposure which suggests that certain segment of DNA strand is resistant to UV-B effects. Similar to the effects on RAPD profile, amplification of rDNA was significantly inhibited following exposure of genomic DNA to UV-B. Our findings clearly demonstrate that UV-B does affect the DNA of cyanobacteria and the killings of these microbes might be due to the irreversible damages caused to DNA by this high energy radiation. It is felt that PCR assay may be conveniently used for screening the damages caused to DNA by UV-B radiation in cyanobacteria and other microorganisms.

Anabaena↗
PubMed2004

Nuclear factor-kappaB: its role in health and disease.

Nuclear factor-kappaB (NF-kappaB) is a major transcription factor that plays an essential role in several aspects of human health including the development of innate and adaptive immunity. The dysregulation of NF-kappaB is associated with many disease states such as AIDS, atherosclerosis, asthma, arthritis, cancer, diabetes, inflammatory bowel disease, muscular dystrophy, stroke, and viral infections. Recent evidence also suggests that the dysfunction of NF-kappaB is a major mediator of some human genetic disorders. Appropriate regulation and control of NF-kappaB activity, which can be achieved by gene modification or pharmacological strategies, would provide a potential approach for the management of NF-kappaB related human diseases. This review summarizes the current knowledge of the physiological and pathophysiological functions of NF-kappaB and its possible role as a target of therapeutic intervention

Animals↗
PubMed2004

Synthesis of some newer derivatives of substituted quinazolinonyl-2-oxo/thiobarbituric acid as potent anticonvulsant agents.

5-[1'-[3"-Aminoacetyl-2"-methyl-6",8"-dihalosubstitutedquinazolin-4"(3"H)-onyl]-thiosemicarbazido]-2-oxo/thiobarbituric acids 3a-3h and 5-[2'-amino-5'-[3"-aminomethylene-2"-methyl-6",8"-dihalosubstitutedquinazolin-4"(3"H)-onyl]-1',3',4'-thiadiazol-2'-yl]-2-oxo/thiobarbituric acid 5a-5h were prepared by incorporating 1-[3'-aminoacetyl-2'-methyl-6",8"-dihalosubstituted-quinazolin-4'(3'H)-onyl]-thiosemicarbazides 2a-2d and 2-amino-5-[3'-aminomethylene-2'-methyl-6',8'-dihalosubstituted-quinazolin-4'(3'H)-onyl]-1,3,4-thiadiazoles 4a-4 h respectively at 5(th) position of 2-oxo/thiobarbituric acids (via Mannich reaction). All the newly synthesized compounds were screened for their anti-convulsant activity in MES and PTZ models and were compared with standard drugs phenytoin sodium and sodium valproate. Interestingly, these compounds were found to be devoid of sedative and hypnotic activities when tested. Out of the compounds studied, the most active compound 5h, that is 5-[2'-amino-5'-[3"-aminomethylene-2"-methyl-6",8"-dibromoquinazolin-4"(3"H)-onyl]-1',3',4'-thiadiazol-2'-yl]-2-thiobarbituric acid showed activity (90%) more potent than the standard drug.

Animals↗
PubMed2004

Enhanced long-term potentiation during aging is masked by processes involving intracellular calcium stores.

The contribution of Ca(2+) release from intracellular Ca(2+) stores (ICS) for regulation of synaptic plasticity thresholds during aging was investigated in hippocampal slices of old (22-24 mo) and young adult (5-8 mo) male Fischer 344 rats. Inhibition of Ca(2+)-induced Ca(2+) release by thapsigargin, cyclopiazonic acid (CPA), or ryanodine during pattern stimulation near the threshold for synaptic modification (5 Hz, 900 pulses) selectively induced long-term potentiation (LTP) to CA1 Schaffer collateral synapses of old rats. Increased synaptic strength was specific to test pathways and blocked by AP-5. Intracellular recordings demonstrated that ICS plays a role in the augmentation of the afterhyperpolarization (AHP) in old rats. The decrease in the AHP by ICS inhibition was reversed by the L-channel agonist, Bay K8644. Under conditions of ICS inhibition and a Bay K8644-mediated enhancement of the AHP, pattern stimulation failed to induce LTP, consistent with the idea that the AHP amplitude shapes the threshold for LTP induction. Finally, ICS inhibition was associated with an increase in the N-methyl-d-aspartate (NMDA) receptor component of synaptic transmission in old animals. This increase in the synaptic response was blocked by the calcineurin inhibitor FK506. The results reveal an age-related increase in susceptibility to LTP-induction that is normally inhibited by ICS and suggest that the age-related shift in Ca(2+) regulation and Ca(2+)-dependent synaptic plasticity is coupled to changes in cell excitability and NMDA receptor function through ICS.

Aging↗
PubMed2004

Dexamethasone inhibits IL-12p40 production in lipopolysaccharide-stimulated human monocytic cells by down-regulating the activity of c-Jun N-terminal kinase, the activation protein-1, and NF-kappa B transcription factors.

IL-12 plays a critical role in the development of cell-mediated immune responses and in the pathogenesis of inflammatory and autoimmune disorders. Dexamethasone (DXM), an anti-inflammatory glucocorticoid, has been shown to inhibit IL-12p40 production in LPS-stimulated monocytic cells. In this study, we investigated the molecular mechanism by which DXM inhibits IL-12p40 production by studying the role of the mitogen-activated protein kinases (MAPKs), and the key transcription factors involved in human IL-12p40 production in LPS-stimulated monocytic cells. A role for c-Jun N-terminal kinase (JNK) MAPK in LPS-induced IL-12p40 regulation in a promonocytic THP-1/CD14 cell line was demonstrated by using specific inhibitors of JNK activation, SP600125 and a dominant-negative stress-activated protein/extracellular signal-regulated kinase kinase-1 mutant. To identify transcription factors regulating IL-12p40 gene transcription, extensive deletion analyses of the IL-12p40 promoter was performed. The results revealed the involvement of a sequence encompassing the AP-1-binding site, in addition to that of NF-kappaB. The role of AP-1 in IL-12p40 transcription was confirmed by using antisense c-fos and c-jun oligonucleotides. Studies conducted to understand the regulation of AP-1 and NF-kappaB activation by JNK MAPK revealed that both DXM and SP600125 inhibited IL-12p40 gene transcription by inhibiting the activation of AP-1 and NF-kappaB transcription factors as revealed by luciferase reporter and gel mobility shift assays. Taken together, our results suggest that DXM may inhibit IL-12p40 production in LPS-stimulated human monocytic cells by down-regulating the activation of JNK MAPK, the AP-1, and NF-kappaB transcription factors.

Adult↗
PubMed2004

Severe hyperthyroidism induces mitochondria-mediated apoptosis in rat liver.

Thyrotoxicosis may be associated with a variety of abnormalities of liver function. The pathogenesis of hepatic dysfunction in thyrotoxicosis is unknown, but has been attributed to mitochondrial dysfunction. We studied the effect of altered thyroid function on the apoptotic index in rat liver. Extensive DNA fragmentation and significantly increased caspase-3 activity (P <.001) and caspase-9 activation (P <.005) were observed in hyperthyroid rat liver; cell death by apoptosis was confirmed. In hyperthyroid rat liver, 60% of mitochondria exhibited disruption of their outer membranes and a decrease in the number of cristae. These findings, along with significant translocation of cytochrome c and second mitochondria-derived activator of caspases to cytosol (P <.005), suggest activation of a mitochondrial-mediated pathway. However, no change in the expression levels of Bcl-2, Bax, and Bcl-x(L) were found in hyperthyroidism. For in vitro experiments, rat liver mitochondria were isolated and purified in sucrose density gradients and were treated with triiodothyronine (T3; 2-8 microM). T3 treatment resulted in an abrupt increase in mitochondrial permeability transition. Using a cell-free apoptosis system, the apoptogenic nature of proteins released from mitochondria was confirmed by observing changes in nuclear morphologic features and DNA fragmentation. Proteins released by 6 microM T3 contained significantly increased amounts of cytochrome c (P <.01) and induced apoptotic changes in 67% of nuclei. In conclusion, using in vivo and in vitro approaches, we provide evidence that excess T3 causes liver dysfunction by inducing apoptosis, as a result of activation of a mitochondria-dependent pathway. Thus, the results of this study provide an explanation for liver dysfunction associated with hyperthyroidism.

Alanine Transaminase↗
PubMed2004

Protection of swiss albino mice against whole-body gamma irradiation by Mentha piperita (Linn.).

The radioprotective effects of Mentha oil (Mentha piperita Linn.) against radiation induced haematological alterations in peripheral blood and the survival of Swiss albino mice were studied. Mentha oil 40 micro L/animal/day for 3 consecutive days when fed orally prior to whole-body gamma irradiation (8 Gy) showed protection of the animals in terms of the survival percentage and haematological parameters in mice. Fifty per cent of the animals died within 20 days and 100% mortality was observed up to 30 days post-irradiation in the control irradiated group. Whereas only 17% of the mice died within 30 days in the experimental group (Mentha oil pretreated irradiated). The total RBC count decreased maximally at 24 h (3.45 +/- 0.20 x 10(12)/L, p < 0.001), similar observations were obtained for the WBC count, haemoglobin content and haematocrit percentage in the irradiated control animals. However, in irradiated animals pretreated with Mentha oil, although the initial values of haematological components were lower they later showed a remarkable recovery reaching normal at 30 days post-irradiation compared with the irradiated control animals. In general, the recovery of the blood cell number in irradiated animals depends on the survival of stem cells and their derivatives. The results from the present study suggest that the oil of Mentha piperita (Linn.) has a radioprotective role in stimulating/protecting the haematopoietic system. Hence, enhanced survival and an increase in the haematological constituents of peripheral blood of mice against lethal gamma radiation was observed.

Administration, Oral↗
PubMed2004

Should laparoscopic cholecystectomy be performed in patients with thick-walled gallbladder?

BACKGROUND/PURPOSE: Laparoscopic cholecystectomy is the procedure of choice for patients with symptomatic cholelithiasis. This procedure is contraindicated in patients with gall-bladder cancer (GBC) because of fear of dissemination of the disease. One of the findings raising the suspicion of GBC is a thick-walled gallbladder (TWGB). METHODS: A prospective study of patients with TWGB was done over a period of 10 months at a tertiary-level referral hospital in northern India. We studied the clinical profiles, investigations (ultrasound [US] and computerized tomography [CT]) and management plans in these patients. RESULTS: A total of 60 patients were included in the study. After cholecystectomy, histopathology of gallbladders showed GBC in 2 (3.3%) patients. The remaining 58 patients had chronic cholecystitis, of whom 28 (48%) had xanthogranulomatous variant chronic cholecystitis. Cholecystectomy by the laparoscopic method was attempted in 46 (77%) patients and by open technique in the remaining 14 (23%) patients. Laparoscopic cholecystectomy was successful in 40 of the 46 (87%) patients in whom it was attempted. Obscure anatomy, suspicion of GBC, and bile duct injury were the causes of conversion, in the remaining 13% (6/46). None of the 11 patients who had a CT examination because of clinical or US suspicion of malignancy turned out to have GBC at final histology. Both the cases of GBC in this study were incidental findings on final histopathology. CONCLUSIONS: Laparoscopic cholecystectomy can be successfully performed in the majority of patients with diffuse TWGB, with appropriate selection. There is, however, an increased chance of conversion to open cholecystectomy in these patients. If there is an intraoperative suspicion of GBC, early conversion to open cholecystectomy and frozen section/imprint cytology will help to decide the further treatment during surgery.

Adolescent↗
PubMed2004

Synthesis and pharmacological evaluation of newer substituted benzoxazepine derivatives as potent anticonvulsant agents.

A series of 2-substitutedphenyl-3-(substitutedphenylamino)methyl-2,3-dihydro-4-diphenylamino-1,5-benzoxazepines (4a-4p) and 2-substitutedphenyl-3-substitutedphenylazo-2,3-dihydro-4-diphenylamino-1,5-benzoxazepines (5a-5p) have been synthesized from 2-substitutedphenyl-2,3-dihydro-4-diphenylamino-1,5-benzoxazepines (3a-3d) by the Mannich reaction and diazotization reaction, respectively. All these compounds were screened, in vivo, for their anticonvulsant activity and acute toxicity studies. Compounds 4p and 5p were found to be most potent compounds of this series and were compared with the reference drug phenytion sodium, lamotrigine and sodium valproate. The structures of these compounds have been established by IR, (1)H NMR and mass spectroscopic data.

Animals↗