PubMed Health⌕ Search

Biomedical subjects

C L Chander

Publications and source records attributed to C L Chander.

At least 19 recordsLinked to original sources
PubMed2000

An investigation into the effect and mechanisms of action of nicotine in inflammatory bowel disease.

OBJECTIVE AND DESIGN: To determine the effect of nicotine on colonic inflammation in the trinitrobenzenesulphonic acid (TNBS) model of inflammatory bowel disease in comparison with sulphasalazine. MATERIALS: Male Wistar rats were used for the in-vivo and ex-vivo studies. In-vitro studies were performed using human leukemia peripheral blood monocyte cells (THP-1 cells) grown in continuous culture. TREATMENT: Rats were given access to either nicotine (5 or 100 microg/mL) or sulphasalazine (375 microg/mL) in their drinking water for 10 or 2 days respectively before and 3 days after TNBS administration. THP-1 cells were treated with nicotine (10(-14) to 10(-11) M) for 2 h before and after stimulation with 3 microg/mL lipopolysaccharide (LPS). METHODS: Inflammation in the TNBS model was assessed by measuring the tissue myeloperoxidase activity, leukotriene B4 concentration, inducible nitric oxide protein expression, the ex-vivo production of tumour necrosis factor alpha (TNFalpha), macroscopic damage score, plasma corticosterone levels and by a qualitative histological evolution. The effect of nicotine on TNFalpha production in LPS stimulated THP-1 monocyte cells in-vitro was also determined. Statistical comparisons were made using the Mann-Whitney U-test for the macroscopic damage score and an ANOVA for all other parameters. RESULTS: TNBS treated rats given access to 100 microg/mL nicotine in their drinking water had a marked reduction in several of the markers of inflammation compared to control TNBS treated rats, but a greater reduction was found at 5 microg/mL nicotine or 375 microg/mL sulphasalazine, the latter producing comparable reductions in inflammation to the low dose nicotine. Nicotine also caused a significant reduction in TNFalpha release from THP-1 cells. CONCLUSIONS: Nicotine reduced inflammation in the TNBS model of colonic damage confirming the use of nicotine in IBD although the choice of dose requires further investigation. The mechanism of action of nicotine does not involve increased corticosterone levels, but may be a consequence of a reduction in TNFalpha or leukotriene B4 production.

Animals↗
PubMed1999

Colony stimulating factors regulate nitric oxide and prostaglandin E2 production in rat cartilage chondrocytes.

Colony stimulating factors (CSFs) are now widely used in cancer treatment and immunological disease therapy. Both granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) are used to increase neutrophil counts in Felty syndrome. In the present study, the effects of macrophage CSF (M-CSF), G-CSF, GM-CSF and interleukin-3 (IL-3) (10 ng/ml) on the production of nitric oxide and prostaglandin E2 (PGE2) by cartilage explants were examined over 24 and 48 h. The effects of these CSFs were also measured in combination with IL-1 beta (10 ng/ml). M-CSF, GM-CSF and IL-3 had no effect on nitrite production. However, both IL-1 beta and G-CSF caused a significant increase (p < 0.05) in nitrite levels at 48 h. NG-L-arginine-methyl-ester was used to inhibit nitrite production induced by G-CSF and this implicated nitric oxide synthase activity. When G-CSF and IL-1 beta were used in a combined treatment, nitrite levels were significantly increased (p < 0.05) at both 24 and 48 h. Both IL-3 alone and in combination with IL-1 beta caused elevated PGE2 production in this model. PGE2 levels were also significantly increased by stimulation with GM-CSF and IL-3 combined with IL-1 beta. These findings demonstrate that GM-CSF, G-CSF and IL-3 may induce changes in the production of inflammatory mediators such nitric oxide and PGE2 in cartilage chondrocytes. Hence, CSFs may play a vital role in influencing cartilage metabolism in rheumatoid and osteoarthritis.

Animals↗
PubMed1996

Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis.

BACKGROUND: Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease. AIM: To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease. METHODS: Amplified chemiluminescence was used to measure reactive oxygen species production by colonic biopsy specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease. RESULTS: The model was validated by demonstrating that the profile of effects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n = 5, p = 0.009) and 88% (n = 5, p = 0.03), respectively. CONCLUSIONS: The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.

Acetic Acid↗
PubMed1994

Generation of lipid peroxidation products in culinary oils and fats during episodes of thermal stressing: a high field 1H NMR study.

The oxidative deterioration of glycerol-bound polyunsaturated fatty acids (PUFAs) in culinary oils and fats during episodes of heating associated with normal usage (30-90 min at 180 degrees C) has been monitored by high field 1H NMR spectroscopy. Thermal stressing of PUFA-rich culinary oils generated high levels of n-alkanals, trans-2-alkenals, alka-2,4-dienals and 4-hydroxy-trans-2-alkenals via decomposition of their conjugated hydroperoxydiene precursors, whereas only low concentrations of selected aldehydes were produced in oils with a low PUFA content, lard and dripping when subjected to the above heating episodes. Samples of repeatedly used, PUFA-rich culinary oils obtained from restaurants also contained high levels of each class of aldehyde. The dietary, physiological and toxicological ramifications of the results obtained are discussed.

Aldehydes↗
PubMed1993

High resolution proton NMR investigations of rat blood plasma. Assignment of resonances for the molecularly mobile carbohydrate side-chains of 'acute-phase' glycoproteins.

An intense broad resonance at 2.14 ppm present in high field (400, 500 and 600 MHz) Hahn spin-echo 1H-NMR spectra of rat blood plasma, but absent from those of human blood plasma is attributable to the presence of terminal O-acetylsialate sugars in the molecularly mobile carbohydrate side-chains of 'acute-phase' glycoproteins (predominantly alpha 1-acid glycoprotein). The presence of such alternative acetylsugars in the carbohydrate side-chains of rat plasma glycoproteins are of much physiological and experimental significance in view of the regular use of these animals in model systems of human inflammatory conditions.

Acute-Phase Proteins↗
PubMed1993

The role of the contractile fibroblast in the capsules around tissue expanders and implants.

The occurrence, structure and contractility of myofibroblasts in the capsules around tissue expanders and static implants has been studied in the rat, pig and humans. The capsules showed a characteristic layered structure with myofibroblasts being the predominant cell type. Capsular strips contract in vitro in a manner characteristic of fibroblast contraction. The contractile ability decreased with the time since expander insertion; and increased with expander exposure, peri-expander infection and clinical evidence of adverse capsular contracture. An hypothesis is proposed that capsular contracture is analogous to wound contraction, and that intraimplant pressure usually inhibits capsular contraction. Evidence is shown from intraexpander pressure measurements to support this hypothesis. The clinical implications for tissue expansion and breast augmentation are discussed.

Animals↗
PubMed1993

Assessment of a human recombinant manganese superoxide dismutase in models of inflammation.

We evaluated a novel human recombinant preparation of manganese superoxide dismutase (MnSOD) for anti-inflammatory and anti-oxidant activity compared with a copper zinc (CuZn) SOD preparation. The results showed that administration of MnSOD (50, 100 and 200 micrograms kg-1) in the Freund's Complete Adjuvant (FCA) mediated paw oedema model suppressed the inflammation at 4 hours by 43, 25 and 43% (P < 0.001, P < 0.01 and P < 0.001 at respective doses). However, 24 hours post-challenge, MnSOD (50 and 100 micrograms kg-1), suppressed the inflammation by 19% (P < 0.001). In contrast, Mn SOD at higher doses (400-800 micrograms kg-1; 2 mgkg-1) exacerbated the inflammatory response at 4 hours. This pro-inflammatory response declined progressively by 24 hours. Furthermore, CuZn SOD produced no significant effects on the inflammatory response. In the carrageenan-induced synovitis model, Mn SOD (25 and 50 micrograms; intra-articular administration) exacerbated the inflammation at 48 hours. In contrast, Mn SOD at 5 micrograms produced a significant suppression (44%, P < 0.05) in knee joint swelling at 24 hours. The CuZn SOD preparation produced marked pro-inflammatory effects in the joints whilst it lacked activity in the FCA-mediated paw oedema model. These findings support a therapeutic potential of MnSOD in inflammatory disorders, however the compound has a complex pharmaco-dynamic profile.

Animals↗
PubMed1992

Effect of endothelin-1 on croton oil-induced granulation tissue in the rat. A pharmacologic and immunohistochemical study.

BACKGROUND: To date no attempts have been made to determine the role of the endothelial cell derived product, endothelin-1 (ET-1) in granulation tissue development. This study investigates the cellular immunolocalization of ET-1 and its pharmacologic effect on myofibroblast-mediated rat croton oil-induced granulation tissue contraction. EXPERIMENTAL DESIGN: The distribution, cellular localization and temporal production of ET-1 in the tissues was determined by immunohistochemistry at days 7, 14, 21, and 28. The contractile response of the granulation tissue to ET-1 was tested over the same time period, and it effects modified by use of calcium antagonists. The pharmacologic profile was correlated to the ultrastructural development of contractile fibroblast-like cells within the tissue. RESULTS: Endothelin-1 caused reversible concentration-dependent contraction of the granulation tissue. The 21-day granulation tissue was the most responsive, with a maximum increase in tension of 458.9 +/- 41.1 mg; this response could be inhibited by use of calcium antagonists. Of the calcium antagonists tested, verapamil (1 x 10(-4) M) was the most potent inhibitor, giving a 43% reduction in maximum amplitude of the response. It is suggested that entry of extracellular calcium via the L-type potential operated calcium channel, is involved in ET-1 induced responses in contractile fibroblast-like cells or myofibroblasts. Ultrastructural analysis showed a correlation between the pharmacologic sensitivity of the tissue and the development of contractile fibroblast-like cells. The number of cells expressing the phenotypic characteristics of a myofibroblast increased with time, and were first observed at day 7. Immunohistochemistry revealed the presence of increasing numbers of ET-1 labeled cells throughout the time course of study. The ET-1 positive cells were localized to the capillaries. Immunolabeling of serial sections with the rodent endothelial cell specific lectin, Bandeiraea simplicifolia isolectin B4 and factor VIII-related antigen, confirmed the specific localization of ET-1 to endothelial cells. CONCLUSIONS: We present evidence that ET-1 may be an endogenous modulator of myofibroblast-mediated granulation tissue contraction and that the use of calcium antagonists could afford a possible therapeutic control in the treatment of fibrocontractive diseases.

Animals↗
PubMed1991

The effects of estrogens on cartilage degradation using in vivo and in vitro models.

We have investigated the effects of estradiol on cartilage breakdown. The model of arthritis used involved the subcutaneous implantation of rat femoral head cartilage (FHCs) into the dorsal region of female mice. The FHCs had been previously wrapped in sterile 5 mg cotton to provoke the growth of granulomatous tissue adjacent to cartilage. Animals were dosed daily, a day after implantation, for 14 days with either 17 beta-estradiol or tamoxifen at different doses. The FHCs were removed and analysed for glycosaminoglycan (GAG) content. The results demonstrated that estradiol accelerated cartilage breakdown in a dose dependent manner, an effect which is blocked by tamoxifen. In addition, estradiol was found to increase cartilage degradation in an in vitro model using FHCs. This effect was enhanced by the addition of fibroblasts.

Animals↗
PubMed1990

The protective effects of cell-free fluid exudate on cartilage degradation in vitro.

In a short-term culture system, polymorphonuclear neutrophils (PMNs) were shown to cause significant loss of glycosaminoglycan (GAG) from cartilage. In addition, a lysate of these cells, and in particular cells stimulated with a phorbol ester, greatly enhanced this loss of GAG. This loss could be partially or completely inhibited by the addition of cell-free fluid exudate to the system. In other long-term culture experiments, IL-1a was shown to enhance fibroblast-induced GAG loss from cartilage. In this system too the breakdown was inhibited by cell-free fluid exudate. Initial characterization of the protective agent or agents shows them to be heat-stable at 56 degrees C and to be non-dialysable. It is proposed that in the chronic inflammatory joint disease, rheumatoid arthritis, the fluid phase of an inflammatory response may have a protective effect against the underlying pathological processes.

Animals↗
PubMed1989

The effect of indomethacin on cartilage breakdown.

The effects of recombinant interleukin-1 alpha (rIL-1 alpha) and indomethacin on the glycosaminoglycan (GAG) content of rat femoral head cartilage (FHC) were studied in vitro. Net GAG loss was observed from cartilage cultured in the presence of indomethacin plus rIL-1 alpha. Indomethacin and rIL-1 alpha alone caused no net loss of GAG from cartilage unless the cartilage was cultured in the presence of fibroblasts.

Animals↗
PubMed1989

Anti-inflammatory effects of endothelin-1.

Endothelin-1 (ET-1), when injected intradermally in rats concurrently with FMLP, did not suppress cell accumulation 6 h later. In view of the fact that ET-1 can antagonize mediators of increased vascular permeability, it is proposed that this is further evidence that fluid and cell accumulation at an inflammatory site are separate processes.

Animals↗
PubMed1989

The effects of heparin and cortisone on an experimental model of pannus.

The effects of heparin and cortisone were investigated in a model of experimental pannus-mediated cartilage degradation. Rat femoral head cartilages were implanted bilaterally (sc.) into female mice either non-wrapped or wrapped in cotton. Animals were treated with tap water (p.o.), heparin 1000 Units (p.o.), cortisone 2 mg/kg (s.c) and heparin-cortisone combined. After 14 days, the implants were removed and analysed for exudate volume, granulation-tissue dry weight and cartilage glycosamino-glycan (GAG) content. In the heparin-treated animals there was a significant (p less than 0.001) increase in the granulation-tissue dry weight, whilst combined treatment significantly (p less than 0.001) reduced both exudate volume and cartilage degradation. It is possible that the effects on angiogenesis may indicate novel treatment for the growth of pannus and cartilage breakdown.

Animals↗
PubMed1989

The chemotactic properties of cartilage glycosaminoglycans for polymorphonuclear neutrophils.

Cartilage breakdown products have been tested for their effects on the locomotion of rat polymorphonuclear neutrophils in vitro. Chondroitin sulphate, keratan sulphate and hyaluronic acid were used in checkerboard migration assays to differentiate chemotaxis from chemokinesis. All test substances showed both chemokinetic and chemotactic activities. The same substances were then injected intradermally to determine their effects on vascular permeability and leukocyte accumulation in vivo. There was no significant effect on vascular permeability 30 minutes after injection as measured by a dye-leakage method. Histological examination of skin sections taken 6 hours after injection showed modest accumulations of polymorphonuclear neutrophils. It is suggested that cartilage breakdown products may account for the persistence of polymorphonuclear neutrophils in some chronic inflammatory joint diseases.

Animals↗