PubMed Health⌕ Search

Biomedical subjects

N S Murthy

Publications and source records attributed to N S Murthy.

At least 19 recordsLinked to original sources
PubMed2005

Flow cytometric analysis of Th1 and Th2 cytokines in PBMCs as a parameter of immunological dysfunction in patients of superficial transitional cell carcinoma of bladder.

Transitional cell carcinoma (TCC) is the commonest cancer of the bladder. Although majority of TCC can be diagnosed at an early stage and removed easily by transurethral resection of tumor (TURT), the management of this carcinoma is complicated due to frequent recurrences usually within 6 months to one-year period. An imbalance between the Th1 and Th2 immune responses has been attributed to immune dysregulation in various malignancies. The present study aims to evaluate the Th1 and Th2 balance in Peripheral Blood Mononuclear Cells of 41 TCC patients (20 recurrent and 21 non-recurrent) using flow cytometry. It also further assesses immunological and cellular factors influencing the anti-neoplastic activity of the TCC patients and in 21 normal healthy subjects in terms of their cytokine expression and various cell surface markers. The findings of the study revealed that the cell surface markers CD3+, CD4+ and CD8+ along with NK cells were found to be significantly lower in patients than healthy controls (p < 0.01). The mean percent expression of CD4+ was significantly lower in patients showing recurrence (23.9 +/- 9.84) as compared to patients with non-recurrence (31.1 +/- 12.27). The percentage of CD4+T-cells (mean +/- SD) producing IFN-gamma, IL-2 and TNF-alpha were statistically significantly reduced in patients (19.1 +/- 4.94, 52.3 +/- 20.86 and 12.8 +/- 4.49) as compared to healthy controls (23.3 +/- 3.67, 67.5 +/- 12.0 and 17.6 +/- 5.96 respectively), (p < 0.01, 0.018, 0.001). On the contrary, the mean levels of IL-4, IL-6 and IL-10 in patients (63.8+/-17.01, 60.4+/-14.79 and 65.7 +/- 14.84 respectively) were significantly higher as compared to healthy controls (24.4 +/- 8.77, 26.5 +/- 5.28 and 20.6 +/- 3.81 respectively), (p < 0.001). No statistically significant difference was observed in the cytokine expression between patients showing recurrence and non-recurrence. Patients with bladder cancer seem to develop a Th2 dominant status with a deficient type1 immune response. The lymphocyte evaluation along with cytokine measurement can provide a sensitive and valuable tool for evaluating the function of cell-mediated immunity in these patients and can also find application in therapeutic monitoring of bladder cancer patients as new targets for immunotherapy.

Adult↗
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↗
PubMed2004

Hydration of proteins: SAXS study of native and methoxy polyethyleneglycol (mPEG)-modified L-asparaginase and bovine serum albumin in mPEG solutions.

Two mPEG-modified globular proteins [mPEG: methoxy poly(ethylene glycol)], and their native unmodified forms, were examined by small-angle x-ray scattering to evaluate the extent of their surface hydration. The effects of free and protein-bound mPEG on the hydration shell were modeled with discrete electron density profiles. We show that an mPEG-depleted layer can account for the decrease in the measured radius of gyration R(g) from 34.1 to 31.1 A in native L-asparaginase, and from 32.4 to 31.0 A in native bovine serum albumin (BSA) in mPEG-containing solvents. For mPEG-modified proteins in mPEG-free solvents, we attribute the observed increase in the R(g) over that of the native proteins (approximately 3% in L-asparaginase, and 10% in BSA) to the presence of mPEG on the protein surface. The R(g) of the mPEG-modified proteins in mPEG solutions generally decrease with mPEG concentration. Relative to the corresponding unmodified protein, this decrease in R(g) is much larger in BSA (from 35.6 to 31.2 A) but much smaller (from 34.9 to 34.3 A) in L-asparaginase. From these studies, the thickness of the hydration layer around L-asparaginase and BSA is estimated to be approximately 15 A. Exclusion of polyols from the protein domain could be related to the presence of the hydration shell around the protein.

Animals↗
PubMed2004

Hepatitis E in pregnancy.

OBJECTIVES: To study the spectrum and the clinical and biochemical course of viral hepatitis E during pregnancy. METHODS: In this prospective study, sera of 62 pregnant women having jaundice in the third trimester of pregnancy were analyzed for markers of hepatitis A, B, C and E viruses. The cord blood samples of hepatitis E virus (HEV)-positive pregnant women at the time of delivery were tested for IgM anti-HEV antibodies by enzyme-linked immunosorbent assay and HEV-RNA by reverse transcriptase polymerase chain reaction. RESULTS: Of the 62 patients, 45.2% had HEV infection and nine developed fulminant hepatic failure (FHF). Eighty-one percent of FHF cases and 37.25% of acute viral hepatitis cases were caused by HEV. Approximately two-thirds of the pregnant women with HEV infection had preterm deliveries. The mortality rate among the HEV-positive pregnant women was 26.9%. Vertical transmission was observed in 33.3% of cases. CONCLUSIONS: One-third of the pregnant women with HEV infection had a severe form of hepatitis in the third trimester of pregnancy, i.e. FHF. Hepatitis E in pregnancy is associated with high rates of preterm labor and mortality.

Adult↗
PubMed2004

Polymorphisms at GSTM1 and GSTT1 gene loci and susceptibility to cervical cancer in Indian population.

Multiple allelism at loci encoding detoxifying enzymes is associated with cancer risk. Glutathione S-transferase (GSTs) catalyzes the conjugation of glutathione to numerous potentially genotoxic compounds. This study evaluates the influence of genetic polymorphisms of GST M1 and GST T1 on susceptibility to cervical cancer. A multiplex polymerase chain reaction method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from cases with cervical cancer (n=142) and normal controls (n=96). The results showed that the frequency of homozygous GSTM1 null genotype was higher in cervical cancer cases (57.0%) as compared to controls (34.4%) and the differences were significant (p<0.05), OR=2.5, 95% CI: 1.4--4.5. The frequency of homozygous GSTT1 null genotype in cancer cases was 19.7% in comparison to 12.5% in controls, however, the difference was not statistically significant (OR=1.7, 95% CI: 0.8-3.8). Significant difference was found between the cases and controls in the distribution of the null genotype of GST M1 in individuals aged above 45 years (p=0.04), but this difference was not significant in individuals aged below 45 years (p=0.06). No significant differences were found in cervical cancer cases and controls when data were analyzed according to age group for GSTT1 null genotype. Further, the combined analysis of both GSTM1 null and GSTT1 null genotypes did not appear to influence the susceptibility to cervical cancer, suggesting that polymorphisms of other detoxifying enzymes may play a significant role in cervical carcinogenesis.

Adult↗
PubMed2003

The prevalence of hepatitis C virus antibodies among the voluntary blood donors of New Delhi, India.

Infection with hepatitis C virus (HCV) is a major cause of transfusion-associated hepatitis, cirrhosis and hepatocellular carcinoma. The present study was conducted with an objective to evaluate the prevalence of anti-HCV antibody in New Delhi, India using a large number of healthy voluntary blood donors. A total of 15,898 healthy voluntary blood donors were subjected to anti-HCV testing (using a commercially available third generation anti-HCV ELISA kit) and 249 were found to be reactive for anti-HCV antibody, yielding an overall prevalence of 1.57%. No significant difference was found between the HCV positivity rate of male (1.57%; 238/15,152) vs. female (1.47%; 11/746) donors, family (1.58%; 213/13,521) vs. altruistic (1.51%; 36/2377) donors and first-time (1.55%; 180/11,605) vs. repeat (1.61%; 69/4293) donors. The age distribution of anti-HCV reactivity showed a maximum prevalence rate of 1.8% in the age group of 20-29 years. In addition, there was a clear trend of decreasing positivity for anti-HCV with increasing age and this trend was statistically significant. The results of the present study show that the prevalence of anti-HCV antibodies in the healthy voluntary blood donors of New Delhi, India is considerably higher than the reported seroprevalence of HCV in majority of the industrialized nations and this represents a large reservoir of infection capable of inflicting significant disease burden on the society. In addition, donors of New Delhi, India showed a trend of decreasing seroprevalence with increasing age, possibly implying a higher exposure rate to HCV in younger subjects.

Adolescent↗
PubMed2003

Polymorphism of the p53 codon 72 Arg/Pro and the risk of HPV type 16/18-associated cervical and oral cancer in India.

Infection of high risk human papillomaviruses (HPVs) specifically the types 16 and 18 has been strongly implicated in the development of cervical cancer. The E6 oncoproteins of these high risk HPVs are known to bind and induce degradation of p53 tumour suppressor protein through the ubiquitin pathways. This degradation is controlled by a common polymorphism of the p53 gene encoding either a proline or an arginine at its codon 72 in exon 4. Recently, it has been demonstrated that the presence of homozygous arginine at codon 72 renders p53 about seven times more susceptible to E6-mediated proteolytic degradation as well as to cervical cancer than those with proline homozygotes or proline/arginine heterozygotes. In India, prevalence of HPV as well as cancers of the uterine cervix and the oral cavity are highest in the world. We have examined this allele-specific predisposition in cervical and oral cancer which is associated with HPV as well as in a non-HPV-linked cancer of the breast. We have carried out investigation in women comprising whole spectrum of cervical lesions with 128 HPV 16/18 positive and 35 HPV negative invasive cervical carcinomas and 34 cases of HPV (16/18) positive and 16 HPV negative cervical dysplasias (mild, moderate and severe) and 104 age-group-matched healthy women as controls. Additionally, we have analysed p53Arg-Pro polymorphism in 13 high risk HPV positive and 31 HPV negative oral cancers along with 20 normal controls and 77 breast cancers with 41 age-matched healthy controls. We observed more than two fold higher risk for homozygous arginine (chi2 = 6.3, df = 2, p = 0.04; OR = 2.3; 95% CI: 1.08-5.16) for HPV 16/18-positive cervical carcinomas when comparison was made only between HPV positive cervical cancers and normal controls but most interestingly, no significant association either in the frequency of homozygous arginine or proline alleles or their heterozygotes could be observed when all the three groups i.e. HPV-positive, HPV-negative cervical cancers and controls were considered simultaneously. No difference was also observed for either arginine or proline polymorphism between women with precancerous lesions of the uterine cervix carrying HPV 16/18 infection and controls. Similarly, increased risk of oral or breast cancer could not be correlated with the polymorphism of arginine/proline allele. Thus the interaction between HPV oncoproteins and the p53 gene polymorphism specifically, homozygous arginine at codon 72 appears to play no role in the development of either cervical or oral cancer and also it can not serve as a biomarker for early identification of cervical, oral or breast cancer.

Adult↗
PubMed2003

Use of antibiotic-loaded polymethyl methacrylate beads in the management of musculoskeletal sepsis--a retrospective study.

OBJECTIVE: To assess the use of antibiotic-loaded polymethyl methacrylate beads in the management of chronic osteomyelitis of different aetiologies: infected osteosynthesis, infected open fractures, and haematogenous osteomyelitis. METHODS: Records of 49 patients with chronic osteomyelitis who were treated at Department of Orthopaedics, Kasturba Medical College, from 1995 to 1999 were studied retrospectively. The diagnosis of chronic osteomyelitis was made on the basis of clinical and radiographic features. Of the 49 patients, 4 had haematogenous osteomyelitis, which later proved to be tuberculosis, and were thus excluded. Antibiotic-loaded acrylic beads were implanted in the remaining patients after thorough debridement. The implant was removed primarily in 16 patients with infected osteosynthesis, who then underwent decompression and sequestrectomy. All wounds were closed primarily. Peri-operative antibiotics were given for 7 days. Beads were removed at the end of 3 weeks followed by bone grafting in 26 patients. Patients were followed up for an average period of 3.7 years. RESULTS: The infective organisms were sensitive to gentamycin in 26 cases and resistant in 19 cases; 14 cases were sensitive to cefuroxime, 11 to cloxacillin, 8 to ampicillin, and 5 to cotrimoxazole. Seven cases were resistant to all antibiotics tested. Of the 19 patients with gentamycin-resistant infection, only one had a poor result. No adverse systemic side-effects such as ototoxicity or nephrotoxicity were seen. Infection did not recur in 39 patients, but 6 patients had low-grade persistent infection at the last follow-up visit. CONCLUSION: In chronic infections, especially those following osteosynthesis, antibiotic beads are a valuable adjuvant. The most valuable advantage is that the wound can be closed primarily, thereby reducing the incidence of nosocomial infections and requirement of nursing care.

Adolescent↗
PubMed2002

Maternal and perinatal outcome in varying degrees of anemia.

OBJECTIVES: To analyze the maternal and perinatal outcome in varying degrees of anemia. METHODS: A total of 447 pregnant women were divided into group I (Hb>11 g%, n=123 women), group II (Hb 9-10.9 g%, n=214 women), group III (Hb 7-8.9 g%, n=79 women) group IV (Hb<7 g%, n=31 women). Their maternal and perinatal outcome, mode of delivery, duration of labor and postpartum complications were noted and analyzed using multiple logistic regression to calculate odds ratios (95% CI) for duration of labor, mode of delivery and low birth babies. Chi square or Fisher's exact test was employed for difference in proportions and Student's t-test for testing difference between means. RESULTS: Mean age (27+/-4.25 years) and number of women with parity >3 were highest in group IV. The patients with Hb<8.9 g% had a 4-6-fold higher risk of prolonged labor compared to Hb>11 g%. The odds ratios for abnormal delivery (cesarean and operative vaginal deliveries) showed a 4.8-fold higher risk (95% CI 1.82, 12.7) in patients with Hb </=7.5 g%. The mean birth weight was maximum in the 9.6-10.5 g% category that fell with both increasing and decreasing hemoglobin values, being lowest in Group IV. Women in Group II had lowest number of low birth weight and IUGR babies, no stillbirths and neonatal deaths, lowest induction and operative delivery rates. CONCLUSIONS: Mild anemia fared best in maternal and perinatal outcome. Severe anemia was associated with increased low birth weight babies, induction rates, operative deliveries and prolonged labor.

Adult↗
PubMed2002

Catheter associated urinary tract infections in neurology and neurosurgical units.

OBJECTIVE: Catheter associated bacteriuria is the most common infection acquired in hospitals. The objective of the study was (1) to study the incidence of bacteriuria following indwelling urethral catheterization in patients with short-term vs long-term catheterization (2) to define the antibiotic resistance pattern among these isolates so that the study can provide guidelines for choosing an effective antibiotic against infections in catheterized patients. METHODS: This is a prospective study carried out over a period of 18 months in Neurology/Neurosurgical patients who had indwelling catheters for > or =48 h. RESULTS: In this study, 68 out of 800 (8.5%) adult inpatients acquired urinary tract infection following indwelling bladder catheterizations. The risk was significantly higher for female, elderly patients, critically ill and patients on prolonged catheterization. Among the bacterial pathogens, Escherichia coli was the commonest organism isolated (32.9%) followed by Pseudomonas sp. (15.1%) and Staphylococcus aureus (12.3%). Candida sp. comprised 13.7% of all isolates. Among Gram negative bacterial pathogens maximum number of isolates were sensitive to Amikacin (sensitivity of 42%). All Gram positive organisms were however sensitive to Vancomycin. CONCLUSIONS: Our results provide guidelines for choosing salvage therapy against hospital resistant strains causing infection in catheterized patients. However, antibiotics seem to prevent urinary tract infections but primarily in patients catherized for short duration, i.e. 3-14 days and not in patients with long-term catheterization.

Aged↗
PubMed2001

Drotaverine hydrochloride vs. valethamate bromide in acceleration of labor.

OBJECTIVES: To compare the efficacy and safety of drotaverine hydrochloride and valethamate bromide in shortening the duration of labor. METHODS: In a randomized controlled trial of 150 nulliparous women in established labor with cervical dilation of 4 cm, 50 women were given drotaverine (group I), 50 women were given valethamate (group II) and another 50 women were not given any medication (group III). Duration of labor, mode of delivery, side effects, and neonatal outcome were measured in all cases. Appropriate non-parametric tests and chi(2) tests were used for assessment of statistical significance. RESULTS: In the three groups, 100%, 96% and 46% women delivered within 6 h, respectively. The injection-to-delivery interval was significantly reduced in the drotaverine group (193.96 min) in contrast to the valethamate group (220.68 min) and control group (412.84 min). The rate of cervical dilation was highest in the drotaverine group (2.04 cm/h) compared with the valethamate bromide group (1.86 cm/h) and control group (1.01 cm/h). There were no major maternal or fetal adverse effects in any group, but minor side effects were more common in the valethamate group. CONCLUSION: Both intramuscular drotaverine hydrochloride and valethamate bromide are effective in acceleration of labor; however, drotaverine accelerates labor more rapidly and is associated with less side effects.

Cervix Uteri↗
PubMed2000

Risk factors for pre-cancerous lesions of the cervix.

Studies on risk factors for pre-cancerous lesions of the uterine cervix have shown strong association with sexual practice. Women with multiple sexual partners and intercourse at early age are at high risk. A role of male partners in further enhancing the risk has been identified. All these support the hypothesis relating to a sexually transmissible aetiological agent. An extensive review of the literature on the risk factors for pre-cancerous lesions of cervix has been carried out. The risk factors were grouped into genital, sexual, chemical, dietary and life factors. Human papilloma virus (HPV) is the major infectious aetiological agent associated with the development of pre-cancerous lesions of cervix. Other co-factors such as multiple sexual partners of the male as well as the female and early age of first intercourse are also involved at the critical aetiological step of progression from low-grade to high-grade lesions. The role of other infectious agents in terms of supportive or interactive effects is not clear. No independent effect for herpes simplex virus 2 on risk is observed. Other risk factors include cigarette smoking, oral contraceptive usage, certain nutritional deficiencies and poor personal hygiene. However, it is not clear whether these factors operate independently from HPV. There is no consistency in the independent effect of these factors on the development of low- to high-grade lesions of cervix. There is a similarity in the patterns of risk between pre-cancerous lesions of the cervix and cervical cancer. Monogamy, late commencement of sexual activity, personal hygiene and use of barrier contraceptive methods help towards primary prevention. In the long-term, primary prevention of cervical neoplasia through HPV immunization of population may be a possibility.

Coitus↗
PubMed2000

The natural history of portal hypertensive gastropathy: influence of variceal eradication.

OBJECTIVE: The natural history and likelihood of bleeding from portal hypertensive gastropathy (PHG) present in patients with portal hypertension before endoscopic variceal obliteration may differ from that in patients who develop PHG during or after variceal eradication. METHODS: A total of 967 variceal bleeders who had achieved variceal eradication by endoscopic sclerotherapy in the recent past were prospectively studied. In all, 88 (9.1%) patients (cirrhosis in 54, noncirrhotic portal fibrosis in 18, and extrahepatic portal vein obstruction in 16) had distinct mucosal lesions. PHG alone was present in 78, PHG with gastric antral vascular ectasia (GAVE) in eight, and GAVE alone in two patients. PHG was graded as mild or severe and according to whether present before (group A) or after endoscopic intervention (group B). Patients underwent regular endoscopy at follow-up to see if the PHG was transitory (disappearing within 3 months), persistent (no change), or progressive. Bleeding from PHG lesions was defined as acute or chronic. RESULTS: Twenty-two (26%) patients had PHG before (group A) and 64 (74%) developed PHG after variceal eradication (group B). During a mean follow-up of 25.1 +/- 14.2 months, PHG lesions disappeared in group A in only two patients (9%), but in group B in 28 (44%) patients (p < 0.05). PHG lesions more often progressed in the former as compared to the latter (18% vs 9.4%, p = NS). The incidence of bleeding was higher in group A than group B (32% vs 4.7%, p < 0.02). Bleeding from PHG occurred in 10 patients (11.6%); seven of them were from group A, and all had either progressive (n = 3) or persistent (n = 4) lesions. CONCLUSIONS: PHG developing after variceal eradication is often transitory and less severe. If PHG is pre-existing, endoscopic therapy for varices could worsen the PHG, with a likelihood of bleeding. Such patients may be benefited by concomitant beta-blocker therapy.

Adolescent↗
PubMed2000

Adrenocorticotropic hormone and growth factor receptors in breast cancer.

Tissues from 100 cases of breast cancer were analysed immunohistochemically for the presence of adrenocorticotropic hormone (ACTH) or ACTH-like peptides and expression of c-erbB-2 oncoprotein, epidermal growth factor receptor (EGF-R) as well as oestrogen receptor (ER). Immunopositivity for ACTH was found in 15% cases of infiltrating duct carcinoma of the breast, whereas 38% and 36% breast tumours were positive for c-erbB-2 and EGF-R respectively. While 27% cases were positive for ER. The immunoexpressions of all parameters were higher in breast cancer cases with upper age group (45 years or above) than the patients below 45 years of age. A significant correlation was observed between the tumour grade and the expression of c-erbB-2 oncoprotein. Further, a positive association between the immunoexpression of c-erbB-2 and EGF-R was noticed. Interestingly, a statistically significant relationship was found between the immunopositivity of ACTH and ER. The study reflects a probable association of ACTH or ACTH-like peptides in pathological process of breast cancer.

Adrenocorticotropic Hormone↗
PubMed1999

Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding.

BACKGROUND AND METHODS: We compared propranolol therapy and endoscopic ligation for the primary prevention of bleeding from esophageal varices. This prospective, controlled trial included consecutive eligible patients who had large varices (>5 mm in diameter) that were at high risk for bleeding. The patients were assigned to either propranolol therapy, at a dose sufficient to decrease the base-line heart rate by 25 percent, or variceal ligation, to be performed weekly until the varices were obliterated or so reduced in size that it was not possible to continue treatment. RESULTS: Of the 89 patients, 82 of whom had cirrhosis of the liver, 44 received propranolol and 45 underwent variceal ligation. The mean (+/-SD) duration of follow-up in each group was 14+/-9 and 13+/-10 months, respectively. The mean time required to achieve an adequate reduction in the heart rate was 2.5+/-1.7 days; the mean number of sessions needed to complete variceal ligation was 3.2+/-1.1. After 18 months, the actuarial probability of bleeding was 43 percent in the propranolol group and 15 percent in the ligation group (P=0.04). Twelve patients in the propranolol group and four in the ligation group had bleeding. Three of the four in the ligation group had bleeding before their varices had been obliterated. Nine patients in the ligation group had recurrent varices, a mean of 3.7 months after the initial treatment. Five patients in each group died; bleeding from the varices was the cause of death of four patients in the propranolol group and of three in the ligation group. There were no serious complications of variceal ligation; in the propranolol group, treatment was stopped in two patients because of side effects. CONCLUSIONS: In patients with high-risk esophageal varices, endoscopic ligation of the varices is safe and more effective than propranolol for the primary prevention of variceal bleeding.

Adrenergic beta-Antagonists↗
PubMed1999

Combination therapy of pentoxifylline and TNFalpha monoclonal antibody in dextran sulphate-induced mouse colitis.

BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) has been suspected of playing an important role in the pathogenesis of inflammatory bowel diseases, and has become a target for the treatment of these diseases. Open-label, placebo controlled studies have shown that engineered CDP571 and chimeric anti-TNF antibody (cA2) provide a significant benefit in Crohn's disease. Since these antibodies have to be used repeatedly to maintain remission in inflammatory bowel disease, there is a concern that their use may compromise host defence and produce toxic side-effects. METHODS: We evaluated the combined use of mouse specific TNFalpha mab (25 microg/mouse, Endogen) and pentoxifylline (PF, 100 mg/kg/day, p.o., TNFalpha release inhibitor) in the DSS (3% dextran sulphate solution) model of mouse colitis. Colitis was induced by the feeding of 3% DSS for three cycles. The study groups were: Group I: single injection of rat anti-mouse IgG, Group II: single injection of TNFalpha mab, Group III: daily PF for three cycles, Group IV: single injection of TNFalpha mab + PF for three cycles, Group V: TNFalpha mab at the beginning of each cycle (three injections) and Group VI: TNFalpha mab (three injections) + daily PF for three cycles. Daily disease activity (DAI) was measured throughout the study. At the end of each cycle, colon tissue was processed for histology, myeloperoxidase (MPO) and plasma TNFalpha. RESULTS: Mice treated with a single injection of TNFalpha alone or TNFalpha mab + PF showed significantly lower DAI, inflammation scores and ulcer index compared with the IgG treated group. Mice treated with TNFalpha mab + PF had no ulcers. Multiple injections of TNFalpha mab or TNFalpha mab + PF showed greater inhibition in DAI and cytokines in the first two cycles. However, in the third cycle, multiple injections of TNFalpha mab showed adverse proinflammatory effects. CONCLUSION: The simultaneous administration of pentoxifylline and TNFalpha mab may enhance therapeutic outcomes in inflammatory bowel disease and reduce the side-effects associated with the repeated use of TNFalpha mab.

Animals↗