A near fatal case of renal colic.
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Aneurysm, Ruptured↗
Biomedical subjects
C J Kelly
Publications and source records attributed to C J Kelly.
Salicylic acid in the serum of subjects not taking aspirin. Comparison of salicylic acid concentrations in the serum of vegetarians, non-vegetarians, and patients taking low dose aspirin.
AIMS: To determine serum salicylic acid concentrations in non-vegetarians and vegetarians not taking salicylate drugs, and to compare these concentrations with those found in patients taking aspirin, 75 mg daily. METHODS: Serum samples were obtained from vegetarians (n = 37) and non-vegetarians (n = 39) not taking salicylate drugs. Non-vegetarians and vegetarians were recruited from the community and from a Buddhist monastery, respectively, in Dumfries and Galloway, Scotland. Patients (n = 14) taking aspirin (75 mg daily) were recruited from the Dumfries diabetic clinic. Serum salicylic acid concentrations were determined using a high performance liquid chromatography method with electrochemical detection. RESULTS: Salicylic acid was detected in every serum sample analysed. Higher serum concentrations of salicylic acid were found in vegetarians than non-vegetarians: median concentrations of 0.11 (range, 0.04-2.47) micromol/litre and 0.07 (range, 0.02-0.20) micromol/litre, respectively; the median of the difference was 0.05 micromol/litre (95% confidence interval for difference, 0.03 to 0.08; p < 0.0001). The median serum concentration of salicylic acid in patients taking aspirin (75 mg daily) was 10.03 (range, 0.23-25.40) micromol/litre, which was significantly higher than that found in non-vegetarians and vegetarians. There was overlap in serum salicylic acid concentrations between the vegetarians and patients taking aspirin. CONCLUSIONS: Salicylic acid, a non-steroidal anti-inflammatory drug, is present in fruits and vegetables and is found in higher concentrations in vegetarians than non-vegetarians. This suggests that a diet rich in fruits and vegetables contributes to the presence of salicylic acid in vivo. There is overlap between the serum concentrations of salicylic acid in vegetarians and patients taking aspirin, 75 mg daily. These findings may explain, in part, the health promoting effects of dietary fruits and vegetables.
Adult↗
Absence of functional inducible NO synthase enhances the efficacy of tolerance induced by high dose antigen feeding.
Recent studies have suggested that IL-12 and IFN-gamma may impair the ability of fed Ag to induce systemic tolerance. Because both of these cytokines can function to directly or indirectly induce inducible NO synthase (iNOS) expression, we have investigated whether the functional expression of iNOS regulates oral tolerance. C57BL/6J wild-type or C57BL/6J NOS2(-/-) mice were gavaged with a single dose of 20 mg of keyhole limpet hemocyanin (KLH), followed by s.c. immunization with KLH/CFA. In the absence of feeding Ag, several parameters of the immune response were more robust in C57BL/6J NOS2(-/-) mice following KLH/CFA immunization, including the magnitude of the delayed-type hypersensitivity response, the proliferative response, and the production of IFN-gamma and IL-2 by Ag-activated draining lymph node cells. These heightened responses in the C57BL/6J NOS2(-/-) mice are still effectively inhibited by feeding KLH. Feeding KLH to the C57BL/6J NOS2(-/-) mice elicited heightened TGF-ss1 production by Ag-activated lymphocytes, as well as augmented total IgG, IgG1, and IgG2a responses to KLH/CFA compared with that seen in Ag-fed wild-type mice. Feeding Ag to the NOS2(-/-) mice suppressed proliferative responses and IFN-gamma production, while increasing IL-4 production and the IgG1/IgG2a ratio even following a booster immunization of KLH/CFA. Administrating L-N:(6)-(1-iminoethyl)-lysine. 2HCl to wild-type mice during the period of Ag feeding reproduced the high TGF-ss1 production seen in Ag-activated lymphocytes from Ag-fed NOS2(-/-) mice. Feeding KLH is followed by transient up-regulation of NOS2 mRNA expression in the Peyer's patches of wild-type mice. Selective inhibition of NOS2 may be a simple way to augment tolerogenic mucosal immune responses.
Administration, Oral↗
Kinetic analysis of a tod-lux bacterial reporter for toluene degradation and trichloroethylene cometabolism.
Kinetics of toluene and trichloroethylene (TCE) degradation and bioluminescence from the bioreporter Pseudomonas putida B2 and TVA8 were investigated utilizing batch and continuous culture, respectively. Degradation was modeled using a Michaelis-Menten expression for the competition of two substrates for a single enzyme system, and bioluminescence was modeled assuming a luciferase enzyme saturational dependence on toluene as the inducer and growth substrate. During the batch experiments, bioluminescence increased at approximately 90 namp/min for initial toluene concentrations of 10 to 50 mg/L, but more slowly at higher toluene concentrations, suggesting maximum promoter induction at below 10 mg/L and toxic effects above 50 mg/L toluene. TCE degradation did not occur until toluene depletion, presumably due to competition between toluene and TCE for the toluene dioxygenase enzyme. During continuous culture, bioluminescence transiently increased, then gradually decreased in response to increasing step changes in toluene feed concentration. Bioluminescence in the CSTR appeared to be limited by growth substrate and/or inducer.
Biodegradation, Environmental↗
Diaphragmatic dysfunction secondary to experimental lower torso ischaemia-reperfusion injury is attenuated by thermal preconditioning.
BACKGROUND: Preconditioning describes the process whereby tissue exposure to a subcritical stress confers protection from subsequent injuries. This study assessed diaphragmatic muscle function after lower torso ischaemia-reperfusion (IR) and the role of thermal preconditioning in attenuation of this injury. METHODS: Sprague-Dawley rats were randomized into three groups (24 per group): a control group, an IR group that had aortic cross-clamping for 1 h followed by reperfusion, and a third group that received thermal preconditioning 18 h before IR. Diaphragmatic function was assessed at 24 h, 48 h and 7 days. RESULTS: IR resulted in significant diaphragmatic twitch and tetanic dysfunction compared with control muscle. Thermal preconditioning significantly attenuated this injury (P < 0.05). Mean(s.e.m.) muscle twitch and tetanic forces in the IR group were 204.9(17.2) and 282.7(19.2) g respectively at 24 h. Corresponding twitch and tetanic forces in preconditioned muscle were 270.4(25.1) and 552.0(35.2) g. CONCLUSION: This study demonstrated that systemic IR injury produced a respiratory muscle mechanical dysfunction that was attenuated by thermal preconditioning, at 24 h, 48 h and 7 days. Preconditioning may have a role in clinical practice, particularly before elective surgery.
Animals↗
Taurine protects against early and late skeletal muscle dysfunction secondary to ischaemia reperfusion injury.
OBJECTIVE: To assess the efficacy of the cytoprotective B-amino acid taurine in prevention of skeletal muscle dysfunction secondary to ischaemia-reperfusion (IR) injury. DESIGN: Randomised controlled animal study. SETTING: Biomedical research laboratory, teaching hospital, Republic of Ireland. ANIMALS: 96 Sprague Dawley rats. INTERVENTIONS: Rats were randomised into three groups (n = 24/group): control (sham); ischaemia-reperfusion (untreated); and ischaemia-reperfusion + taurine. A further 24 rats were given taurine alone. The rat cremaster skeletal muscle model of four hours of ischaemia followed by reperfusion was used. Taurine 4%wt/vol was given in the animals' water throughout the experiment, beginning 48 hours before the ischaemia was initiated. OUTCOME MEASURES: 8 rats were killed from each group and muscle contractile function was assessed using electrical field stimulation in a tissue bath at 24 hrs, 48 hrs and 7 days. RESULTS: Ischaemia followed by 24 hours, 48 hours or 7 days of reperfusion resulted in significant reduction in both muscle twitch and tetanic contractile function (p < 0.05). This was reversed by taurine, which resulted in significant preservation of twitch and tetanic contractility at all time points including one week of reperfusion (p < 0.05). There was no difference in muscle function between muscle treated with taurine after ischaemia-reperfusion and control muscle, with the same operation but without ischaemia, from 48 hours onwards. CONCLUSIONS: These data show that pharmaceutical use of the endogenous amino acid taurine, unlike many-other agents, protects electrophysiological function in skeletal muscle against both early and late ischaemia-reperfusion injury.
Animals↗
The long term health consequences of polycystic ovary syndrome.
Women with polycystic ovary syndrome have both insulin resistance and beta cell dysfunction. Consequently, they are at increased risk of developing diabetes and cardiovascular disease. Women with polycystic ovary syndrome present to clinicians at a young age and as such offer a unique opportunity to identify insulin resistant patients at an early stage. This enables the modification of risk factors and diagnosis of diabetes before the onset of macro- and micro-vascular symptoms. Increased emphasis should thus be placed on long term risk management and diabetic screening with advice on smoking, exercise and, if appropriate, weight loss. Where possible drugs that exacerbate insulin resistance should be avoided and consideration should be given to the use of insulin sensitising agents, particularly in the obese.
Diabetes Mellitus, Type 2↗
Taurine prevents interleukin-2-induced acute lung injury in rats.
BACKGROUND: The therapeutic efficacy of interleukin-2 (IL-2) has been limited by a dose-dependent vascular leak syndrome. This may be related to neutrophil-mediated endothelial injury. Taurine has been shown to decrease this injury in vitro. This study investigates the role of taurine in preventing IL-2-induced lung injury, and the role of neutrophil-endothelial interactions in mediating this injury. METHODS: Study 1: Sprague-Dawley rats (n = 12/groups) were randomised to controls, IL-2-treated (1 x 10(6) units), and IL-2-treated with taurine (4% solution, orally for 48 h prior to IL-2 therapy). Lung injury was measured by extravascular lung water (wet/dry weight) and bronchoalveolar lavage protein concentration. Neutrophil infiltration was evaluated by measuring myeloperoxidase activity and bronchoalveolar lavage neutrophil concentration. Study 2: Rats (n = 10/group) were randomised into the same groups as study 1. Neutrophil-endothelial interactions in mesenteric vessels were assessed by intravital microscopy at half-hourly intervals. RESULTS: Taurine reduced IL-2-induced acute lung injury as reflected by a decrease in wet-to-dry lung weight ratio from 7.2 +/- 0.5 in the IL-2 group to 4.7 +/- 0.3 in the taurine group (p < 0.05), and a decrease in bronchoalveolar neutrophil concentration from 823 +/- 19.5 in the IL-2 group to 538 +/- 18 in the taurine group (p < 0.05). Intravital microscopy demonstrated that IL-2 increased leucocyte adhesion and migration in mesenteric vessels, and that this was significantly reduced by taurine. CONCLUSION: These data suggest that taurine prevents IL-2-induced tissue injury in part by decreasing neutrophil-endothelial interactions.
Acute Disease↗
Implementation of guidelines for HIV counseling and voluntary HIV testing of pregnant women.
OBJECTIVES: This study assessed HIV counseling and testing among pregnant women. METHODS: A survey was administered to 9115 women who gave birth at 66 Chicago-area hospitals in 1997 and 1998. RESULTS: Fifty-eight percent of the women received HIV counseling, and 65% were offered testing. Fifty-six percent were tested for HIV. Among the women tested, 88% were given their test result. Women were more likely to be tested if they received HIV counseling and were more likely to be offered testing if they received such counseling. CONCLUSIONS: Rates of HIV counseling for, and offers of testing to, pregnant women need to be increased.
AIDS Serodiagnosis↗
An emerging role for agmatine.
Polyamines, required components of proliferation, are autoregulated by the protein antizyme. To date, agmatine is the only molecule other than the polyamines that can induce antizyme, and thus influence cell homeostasis and growth. Agmatine has effectively suppressed proliferation in immortalized and transformed cell lines. An increased sensitivity to the anti-proliferative effects of agmatine observed in Ras transformed versus native cells paralleled an increase in agmatine uptake in the transformed cells. We hypothesize that agmatine may target transformed cells via selective transporters.
Agmatine↗
Recombinant human manganese superoxide dismutase attenuates early but not delayed skeletal muscle dysfunction following reperfusion injury.
OBJECTIVES: to assess the efficacy of recombinant human manganese superoxide dismutase (rhMnSOD) in prevention of early and late skeletal muscle ischaemia-reperfusion injury mediated by superoxide (O2-). Design : randomised controlled trial. MATERIALS: seventy-two Sprague-Dawley rats (250-350 g) randomised to receive either 7.5 mg/kg of rhMnSOD or saline. Four hours of ischaemia was induced in the cremaster muscle by dissecting free and clamping its vascular supply. Cremaster muscle contractile function was assessed following 90 minutes, 24, 48 hours and one week of reperfusion. Electrophysiological muscle function was assessed using electrical field stimulation in an organ bath system. RESULTS: muscle function in the untreated groups following ischaemia reperfusion was significantly reduced at 90 minutes, 24, 48 hours and one week of reperfusion (p <0.05). rhMnSOD significantly protected and maintained normal muscle function at 24 and 48 hours (p <0.001). However at one week of reperfusion there was a reduction in function of the treated muscle, such that there was no significant difference between treated and untreated muscle at this point in time. CONCLUSIONS: these data demonstrate that skeletal muscle dysfunction after ischaemia reperfusion injury is attenuated at 24 and 48 hrs of reperfusion by the superoxide scavenger rhMnSOD. This protective effect is not maintained after seven days of reperfusion.
Animals↗
Vitamin C reduces ischaemia-reperfusion-induced acute lung injury.
OBJECTIVES: to evaluate vitamin C supplementation in the prevention of ischaemia-reperfusion (I-R) induced acute lung injury. DESIGN: Sprague-Dawley rats (n =6/group) were randomised into Control, I-R and I-R pretreated with vitamin C (3.3 g over 5 days). Ischaemia-reperfusion injury was induced by 30 minutes infrarenal aortic cross-clamping and 120 minutes reperfusion. METHODS: pulmonary microvascular injury was measured by broncho-alveolar lavage protein concentration, pulmonary neutrophil infiltration by tissue myeloperoxidase activity and bronchoalveolar lavage neutrophil counts. In a second experiment (n =5/group) neutrophil respiratory burst activity was measured in Control and vitamin C groups. RESULTS: ischaemia-reperfusion resulted in a significant increase in both microvascular leakage and pulmonary neutrophil infiltration as measured by bronchoalveolar lavage protein concentration and pulmonary myeloperoxidase activity respectively. Pretreatment with vitamin C significantly attenuated both microvascular leakage and neutrophil infiltration. Neutrophil respiratory burst activity was significantly reduced in the vitamin C group (13.02 m.c.f.+/-0.3) compared with Control (19.04 m.c.f.+/-1. 9),p <0.02. CONCLUSION: these data suggest that oral vitamin C therapy protects against ischaemia-reperfusion-induced acute lung injury, possibly by attenuating neutrophil respiratory burst activity.
Animals↗
Regulation of intracellular polyamine biosynthesis and transport by NO and cytokines TNF-alpha and IFN-gamma.
Nitric oxide (NO) has been described to exert cytostatic effects on cellular proliferation; however the mechanisms responsible for these effects have yet to be fully resolved. Polyamines, conversely, are required components of cellular proliferation. In experimental models of inflammation, a relationship between these two pathways has been suggested by the temporal regulation of a common precursor, arginine. This study was undertaken to determine the effects NO and the NO synthase (NOS)-inducing cytokines, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), exert on polyamine regulation. The transformed kidney proximal tubule cell line, MCT, maintains high constitutive levels of the first polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). NO donors markedly suppressed ODC activity in MCT and all other cell lines examined. TNF-alpha and IFN-gamma induction of NO generation resulted in suppressed ODC activity, an effect prevented by the inducible NOS inhibitor L-N6-(1-iminoethyl)lysine (L-NIL). Dithiothreitol reversal of NO-mediated ODC suppression supports nitrosylation as the mechanism of inactivation. We also evaluated polyamine uptake, inasmuch as inhibition of ODC can result in a compensatory induction of polyamine transporters. Administration of NO donors, or TNF-alpha and IFN-gamma, suppressed [3H]putrescine uptake, thereby preventing transport-mediated reestablishment of intracellular polyamine levels. This study demonstrates the capacity of NO and inflammatory cytokines to regulate both polyamine biosynthesis and transport.
3T3 Cells↗
Cellular immunity and the tubulointerstitium.
In the past two decades, there has been an increasing appreciation of the relationship between alterations in the interstitial compartment of the kidney and decrements in glomerular filtration rate. In human renal disease, injury patterns in the interstitial compartment consist of a spectrum from predominantly inflammatory to predominantly fibrotic. This review synthesizes information on the pathogenesis of inflammatory interstitial nephritis into a conceptual framework for understanding this important form of human renal disease.
Epitopes↗
Nitric oxide in interstitial nephritis and other autoimmune diseases.
Nitric oxide can be generated by macrophages, as well as many other cell types, through a cytokine inducible isoform of nitric oxide synthase. Historically the effector functions ascribed to iNOS-generated NO have been the control of intracellular organisms and tumor cell cytotoxicity. However, there is a growing appreciation that iNOS generated NO can additionally play an important role in immunoregulation. In this review, the authors outline the effects of iNOS inhibition or genetic deletion on the expression of several autoimmune diseases and discuss potential mechanisms underlying the immunosuppressive effects of NO.
Animals↗
Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels.
Polyamines are required for entry and progression of the cell cycle. As such, augmentation of polyamine levels is essential for cellular transformation. Polyamines are autoregulated through induction of antizyme, which represses both the rate-limiting polyamine biosynthetic enzyme ornithine decarboxylase and cellular polyamine transport. In the present study we demonstrate that agmatine, a metabolite of arginine via arginine decarboxylase (an arginine pathway distinct from that of the classical polyamines), also serves the dual regulatory functions of suppressing polyamine biosynthesis and cellular polyamine uptake through induction of antizyme. The capacity of agmatine to induce antizyme is demonstrated by: (a) an agmatine-dependent translational frameshift of antizyme mRNA to produce a full-length protein and (b) suppression of agmatine-dependent inhibitory activity by either anti-antizyme IgG or antizyme inhibitor. Furthermore, agmatine administration depletes intracellular polyamine levels to suppress cellular proliferation in a transformed cell line. This suppression is reversible with polyamine supplementation. We propose a novel regulatory pathway in which agmatine acts as an antiproliferative molecule and potential tumor suppressor by restricting the cellular polyamine supply required to support growth.
3T3 Cells↗
The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation.
The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors that is predominantly expressed in adipose tissue, adrenal gland and spleen. PPAR-gamma has been demonstrated to regulate adipocyte differentiation and glucose homeostasis in response to several structurally distinct compounds, including thiazolidinediones and fibrates. Naturally occurring compounds such as fatty acids and the prostaglandin D2 metabolite 15-deoxy-delta prostaglandin J2 (15d-PGJ2) bind to PPAR-gamma and stimulate transcription of target genes. Prostaglandin D2 metabolites have not yet been identified in adipose tissue, but are major products of arachidonic-acid metabolism in macrophages, raising the possibility that they might serve as endogenous PPAR-gamma ligands in this cell type. Here we show that PPAR-gamma is markedly upregulated in activated macrophages and inhibits the expression of the inducible nitric oxide synthase, gelatinase B and scavenger receptor A genes in response to 15d-PGJ2 and synthetic PPAR-gamma ligands. PPAR-gamma inhibits gene expression in part by antagonizing the activities of the transcription factors AP-1, STAT and NF-kappaB. These observations suggest that PPAR-gamma and locally produced prostaglandin D2 metabolites are involved in the regulation of inflammatory responses, and raise the possibility that synthetic PPAR-gamma ligands may be of therapeutic value in human diseases such as atherosclerosis and rheumatoid arthritis in which activated macrophages exert pathogenic effects.
Bone Marrow Cells↗
Herbimycin-A attenuates ischaemia-reperfusion induced pulmonary neutrophil infiltration.
OBJECTIVES: To determine whether pharmacological induction of heat shock proteins (HSPs) by herbimycin-A (a tyrosine-kinase inhibitor) would protect against neutrophil-mediated lung injury in an animal model of lower torso ischaemia-reperfusion. MATERIALS AND METHODS: Sprague-Dawley rats were randomised into three groups: the control group underwent midline laparotomy only; the ischaemia-reperfusion (IR) group underwent laparotomy and clamping of the infrarenal abdominal aorta for 30 min followed by 2 h of reperfusion; the third group (HerbIR) was pretreated with herbimycin-A 18 h prior to IR insult. Wet to dry lung weight ratio (W:D), bronchoalveolar lavage protein concentration (BALprot), tissue myeloperoxidase activity (MPO) and bronchoalveolar lavage neutrophil count (BALPMN) were measured. Heat shock protein 72 (HSP72) expression in lung, intestine, mesentery and liver was measured using Western immunoblotting. RESULTS: IR resulted in acute lung injury with tissue oedema (W:D) and neutrophil infiltration (PMO, BALPMN). Herbimycin-A, in vivo, induced HSP expression and attenuated neutrophil infiltration (MPO, BALPMN). CONCLUSION: These data indicate that herbimycin-A protects against ischaemia-reperfusion induced pulmonary neutrophil infiltration, possibly by increasing the expression of heat shock proteins.
Animals↗