Nitric Oxide Synthetase Activity Research Articles

NO/NOS system in prostate cancer

Via activating G-protein receptor transduction pathways,nitric oxide (NO),an important signal molecule,has a complex and diverse role which is closely related with activity and gene expression of nitric oxide synthetase (NOS).NO is involved in tumor related events such as cellular proliferation,migration,especially the angiogenic process,and it is closely related with the occurrence and progression of prostate cancer.NO donors and NOS inhibitors have anti-cancer and radio-chemotherapy enhancement roles. Key words: Nitric oxide; Nitric oxide synthase; Prostatic neoplasmas; Angiogenesis modulating agents

Rutaecarpine inhibits angiotensin II-induced proliferation in rat vascular smooth muscle cells

To evaluate the effects and possible mechanisms of rutaecarpine on angiotensin II (Ang II)-induced proliferation in cultured rat vascular smooth muscle cells (VSMCs). VSMCs were isolated from Male Sprague-Dawley rat aorta, and cultured by enzymic dispersion method. Experiments were performed with cells from passages 3-8. The cultured VSMCs were randomly divided into control, model (Ang II 0.1 μmol/L), and rutaecarpine (0.3-3.0 μmol/L) groups. VMSC proliferation was induced by Ang II, and was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and cell counting. To examine the mechanisms involved in anti-proliferative effects of rutaecarpine, nitric oxide (NO) levels and NO synthetase (NOS) activity were determined. Expressions of VSMC proliferation-related genes including endothelial nitric oxide synthase (eNOS), and c-myc hypertension related gene-1 (HRG-1) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR). Rutaecarpine (0.3-3.0 μmol/L) inhibited Ang II-induced VSMC proliferation and the best effects were achieved at 3.0 μmol/L. The Ang II-induced decreases in cellular NO contents and NOS activities were antagonized by rutaecarpine (P <0.05). Ang II administration suppressed the expressions of eNOS and HRG-1, while increased c-myc expression (P <0.05). All these effects were attenuated by 3.0 μmol/L rutaecarpine (P <0.05). Rutaecarpine is effective against Ang II-induced rat VSMC proliferation, and this effect is due, at least in part, to NO production and the modulation of VMSC proliferation-related gene expressions.

Sub-cytotoxic Concentration of AflatoxinB2 Prevents NO-Mediated Increased Mitochondrial Membrane Potential and Intracellular Killing of &lt;i&gt;Candida albicans&lt;/i&gt; in MacrophagesRunning Title: Changes of Nitric Oxide and Mitochondrial Membrane Potential by Aflatoxin

Aflatoxin B2 (AFB2) is a carcinogenic and immunotoxic metabolite produced by Aspergillus flavus growing on crops and food. The immune functions of rat macrophages when exposed to sub-cytotoxic concentrations of AFB2 which may make exposed people susceptible to Candida albicans infections, have been assessed. This level of AFB2 significantly prevents immune functions of macrophages by inhibiting nitric oxide (NO) production, mitochondrial membrane potential and intracellular killing of C.albicans by macrophages even in the presence of activating signal, interferon-γ. AFB2-induced prevention of increased membrane potential and intracellular killing of C.albicans by macrophages may be due to the prevention of iNOS (inducible nitric oxide synthetase) activity which results in the suppression of NO production. This study provides an important clue to the possibility that macrophages may give refuge to C.albicans for survival and dissemination and thus C.albicans is capable of inducing self-protective effect by the action of AFB2. The presence of AFB2 would thus help the macrophages to allow the C.albicans to replicate and persist, while being invisible to the immune system. This plausibility will give impetus to medicinal development.

Omega-3 fatty acids improve psychomotor performance via mechanism not related to nitric acid production

Omega-3 fatty acids (ω-3FAs) are essential polyunsaturated fats that protect the brain from cognitive impairment. It increases the activity of endothelial nitric oxide synthetase (eNOS) and thereby increases the nitric acid (NO) production. This study aimed to explore the effect of ω-3FAs on psychomotor performance and to relate this effect to the reactive nitrogen species. This study was conducted in Department of Pharmacology, College of Medicine, Al-Mustansiriya University in Baghdad, Iraq. Twenty healthy subjects, allocated randomly from medical college students, were participated in the single blind clinical trial. Participants were divided into two groups, each of ten subjects to receive either placebo or (ω-3FAs) (750 mg single oral dose daily for 5 days). They were asked to perform psychomotor performance before and after 5 days of treatment, and venous blood was obtained for determination of serum nitric oxide (NO) and peroxynitrite (ONOO). ω-3FAs treated group was significantly different from placebo-treated group in reducing choice and motor reaction times as well as the critical flicker frequency threshold. The serum levels of NO and ONOO in ω-3FAs-treated group did not significantly differ from placebo-treated group. Short term supplementation of ω-3FAs improves the psychomotor performance in young healthy subjects via a mechanism not related to the production of nitric oxide production. Inflorescence is a panicle few flowered and fruit is a capsule. The data of the results obtained were presented and discussed. Key words: Nitrogen species, psychomotor performance, ω-3FAs

An emerging problem in clinical practice: how to treat chronic headache patients

In this issue, an interesting article by Farinelli and coworkers [1] debates an important emerging and not yet resolved problem: how to treat the chronic headaches complicated by medication overuse. Headache is the most common neurological disease in clinical practice. In Europe, this affects about 51% of the population, of which 31% are tension-type headache and 14% are migraine sufferers; 2% of these patients become chronic sufferers, more than 15/day/month, and chronic daily headache (CDH). 4–5% of general population suffers from a chronic form (CDH), with prevalence between 1.7 and 2.1% in men and between 2.8 and 6.8% in women [2]; within this group of patients in the US general population ranges around 1.3–2% of chronic migraine (CM). A number of possible pathophysiological mechanisms for the transformation from episodic to chronic headache have been proposed including a progressive damage of the central nociceptive system. One physiopathological hypothesis is the activation of N-methyl-D-aspartate (NMDA) and nonNMDA receptors glutamate, released by central nociceptive terminations, induces calcium entry in dorsal horn neurons, as well as in the trigeminal nucleus caudalis. Calcium entry leads to the activation of nitric oxide (NO) synthetase causing NO synthesis. These neurotransmitters produce the release of sensory neuropeptides, such as CGRP and substance P, which support the development of hyperalgesia and maintain central sensitization [3–5]. Medication near-daily use and subsequent medication overuse headache (MOH) have been described by the revised International Classification of Headache Disorders (ICHDs)-IIR criteria as the use of each drug for at least 3 months, for a certain number of days per month, and is one of the most critical parameters in the process of

Decreased glutamine synthetase, increased citrulline–nitric oxide cycle activities, and oxidative stress in different regions of brain in epilepsy rat model

To understand their role in epilepsy, the nitric oxide synthetase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS), and total antioxidant status (TAS), were estimated in different regions of brain in rats subjected to experimental epilepsy induced by subcutaneous administration of kainic acid (KA). The short-term (acute) group animals were killed after 2h and the long term (chronic) group animals were killed after 5days of single injection of KA (15mg/kg body weight). After decapitation of rats, the brain regions were separated and in their homogenates, the concentration of NOx, TBARS and TAS and the activities of NOS, AS, AL, arginase and glutamine synthetase were assayed by colorimetric methods. The results of the study demonstrated the increased activity of NOS and formation of NO in acute and chronic groups epilepsy. The activities of AS and AL were increased and indicate the effective recycling of citrulline to arginine. The activity of glutamine synthetase was decreased in acute and chronic groups of epilepsy compared to control group and indicate the modulation of its activity by NO in epilepsy. The activity of arginase was not changed in acute group; however it was decreased in chronic group and may favor increased production of NO in this condition. The concentration TBARS were increased and TAS decreased in acute and chronic groups of epilepsy and supports the oxidative stress in epilepsy.

Assessment and comparison of immunoregulatory activity of four hydrosoluble fractions of Angelica sinensisin vitro on the peritoneal macrophages in ICR mice

Angelica sinensis (Oliv) Diels, a traditional oriental herbal medicine, is known to have immunostimulatory and antitumor effects. In this paper, four hydrosoluble fractions were obtained and purified from A. sinensis including: Angelica polysaccharide, oligosaccharides (Angelica oligosaccharide and Angelica sucrose) and Angelica total amino acid, named APS, AOS, AS, and TAA, respectively. Moreover, the immunomodulatory activity of these four fractions on murine peritoneal macrophages were assessed and compared from various aspects including cell proliferation, phagocytic activity, nitric oxide (NO) and hydrogen peroxide (H 2O 2) release, induced nitric oxide synthetase (iNOS) and lysozyme (LZM) activity, intracellular adhesion molecule-1 (ICAM-1) expression on cell surface and Toll-like receptor 4 (TLR4) gene expression. Although APS exhibited the most obvious growth facilitative activity, AOS did better in activation of H 2O 2 release; TAA exerted the best activation of phagocytic activity, production of NO and ICAM-1 expression. Furthermore, we found that the action mode of the four fractions was similar to that of LPS and the mechanism may be related to the upregulation of TLR4 mRNA. These results demonstrated that oligosaccharide and amino acid fractions, as well as polysaccharide fraction of Radix A. sinensis, could serve as immunomodulator and TLR4 as one of the immune receptors may play important role for this action.

Antidiabetic properties of purified polysaccharide fromHedysarum polybotrys

Hedysarum polybotrys polysaccharide (HPS) is the principal active fraction responsible for the antidiabetic properties of this species. The aim of this study was to determine the antidiabetic properties of 4 purified fractions of different molecular weight range HPSs (HPS1, HPS2, HPS3, HPS4). HPS3 was selected for examination of its hypoglycemic mechanism because of its significant hypoglycemic effect in alloxan-induced diabetic mice. The changes in blood glucose levels and oral glucose tolerance tests (OGTT) showed that hypoglycemia was more pronounced in HPS3-treated groups than in the diabetes mellitus model (DM) control group. The interleukin-6, tumor necrosis factor-alpha, leptin, and free fatty acid levels were significantly lower in the HPS3-treated groups and HPS3 + metformin (HPS3+MET) group than in the DM control group, while plasma insulin, hepatic glycogen, superoxide dismutase, and nitric oxide synthetase activity were significantly higher. Treatment with HPS3 or HPS3+MET also significantly lowered malonaldehyde levels compared with the DM control group, while it elevated the nitric oxide and total antioxidant capacity. HPS3 altered the plasma lipid levels by lowering cholesterol and triglyceride concentrations, while elevating the plasma high-density lipoprotein cholesterol level. Therefore, these results suggest that HPS3 may partly ameliorate hyperglycemia and hyperlipidemia associated with type 2 diabetes through increased insulin secretion, inhibition of lipid peroxidation, promotion of sensitivity to insulin, suppression of gluconeogenesis and reduction in the biosynthesis fatty acid, cholesterol and cell cytokines related to insulin resistance, and it could be a useful adjunct therapy to a proven first-line therapy for type 2 diabetes using metformin.

Review article: nitric oxide from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis

Factors initiating human ulcerative colitis (UC) are unknown. Dysbiosis of bacteria has been hypothesized to initiate UC but, to date, neither the nature of the dysbiosis nor mucosal breakdown has been explained. To assess whether a dysbiosis of anaerobic nitrate respiration could explain the microscopic, biochemical and functional changes observed in colonocytes of UC. Published results in the gastroenterological, biochemical and microbiological literature were reviewed concerning colonocytes, nitrate respiration and nitric oxide in the colon in health and UC. A best-fit explanation of results was made regarding the pathogenesis and new treatments of UC. Anaerobic nitrate respiration yields nitrite, nitric oxide (NO) and nitrous oxide. Colonic bacteria produce NO and UC in remission has a higher lumenal NO level than control cases. NO with sulphide, but not NO alone, impairs beta-oxidation, lipid and protein synthesis explaining the membrane, tight junctional and ion channel changes observed in colonocytes of UC. The observations complement therapeutic mechanisms of those probiotics, prebiotics and antibiotics useful in treating UC. The prolonged production of bacterial NO with sulphide can explain the initiation and barrier breakdown, which is central to the pathogenesis of UC. Therapies to alter bacterial nitrate respiration and NO production need to evolve. The production of NO by colonic bacteria and that of the mucosa need to be separated to pinpoint the sequential nature of NO damage in UC.

Role of Cytokines during Epileptogenesis and in the Transition from the Interictal to the Ictal State in the Epileptic Mutant EL Mouse

Purpose Epileptic mutant EL mice show secondary generalized seizures. Seizure discharges initiate in the parietal cortex and generalize through the hippocampus. We have previously demonstrated an increase in the activity of inducible nitric oxide synthetase (iNOS) as well as a decrease in the activity of superoxide dismutase (SOD) in the hippocampus of EL mice, suggesting that cell toxic free radicals are increased in the brain of EL mice. In parallel with this, neurotrophic factors were significantly increased in the hippocampus of EL mice in earlier developmental stages before exhibiting frequent seizures. These findings were no longer present after frequent seizures, suggesting that these events may trigger ictogenesis. On the other hand, it is reported that limbic seizures rapidly induce cytokines and related inflammatory mediators. It remains to be seen, however, whether cytokines contribute to the transition from interictal to ictal state. The present study was designed to address this issue using EL mice. Methods EL mice at the age from 4 to 23 weeks and their control animal, DDY mice at the age of 10 and 20 weeks were used. Seizures were induced in EL mice once every week since 5 weeks. Cytokines, such as interleukin-1 alpha (IL-1a), interleukin 1-beta (IL-1b), IL-6, IL-1 receptor (IL-1r), IL-1 receptor antagonist (IL-ra) and tumor necrosis factor alpha (TNF-a) were examined by Western blotting in the ‘focus complex’ of brain (namely, in the parietal cortex and hippocampus) of EL mice in the interictal period at different developmental stages. In 15 week old EL mice, which show seizures once a week, these cytokines were similarly determined 5 min, 2 hr, 4 hr, 11 hr, 24 hr, 3 days and 6 days after the last seizure induced. Results A significant increase in the level of cytokines was observed in the brain of EL mice at any stages during development, compared with the level of cytokines in the brain of control DDY. Cytokines were increased predominantly before experiencing frequent seizures. In EL mice at the age of 15 weeks, the level of cytokines in the hippocampus was highest 6 days after seizures. In the parietal cortex, cytokines were most highly expressed 2 hr after seizures. The results indicate that cytokines were kept up-regulated until next seizures in the hippocampus, whereas they were transiently up-regulated immediately after seizures in the parietal cortex. Conclusion It is concluded that in the brain of EL mice, pro-inflammatory cytokines are increased progressively and periodically in association with the development and the seizure activity, respectively. A periodic increase of cytokines prior to the next seizure episode may play a role in triggering the ictal activity. Namely, alteration of region-specific cytokines may induce ictal activities from the interictal state. It is conceivable that inflammatory cytokines may work together with neuronal factors during epileptogenesis and in the transition from interictal to ictal state.

Modification of phenylephrine induced contraction of human vessel rings by L-arginine and L-arginine methyl ester

Endothelial dysfunction is associated to a lower production of nitric oxide and a reduction of endothelium mediated vasodilation. To study the effects of pharmacological agents that modify nitric oxide synthetase (NOS) activity on tension changes induced by phenylephrine in rings of internal mammary and radial arteries and saphenous vein. Vessel rings of 7 to 10 mm length were obtained from 32 patients subjected to coronary vascular surgery Fourteen samples of radial artery, 12 samples of internal mammary artery and 15 samples of saphenous vein were obtained. A maximal contraction was induced with KC1 and dose response curves for phenylephrine (FE) in the absence or presence of L-arginine and L-arginine methyl ester (L-NAME), were constructed. The tension induced by FE in internal mammary artery and saphenous vein reached a maximum, near 90% of 80 mM KCl-induced contraction, but in the radial artery, it reached a maximum of 63% (p <0.05). In all vessels, the dose response curves were significantly shifted to the right by L-arginine and to the left by L-NAME. Pre-incubation of human rings with L-ARG or L-NAME, changed the response to FE induced contraction, which may be related to different degrees of endothelial nitric oxide production or NO sensitivity. The basal NO production in radial artery seems to be larger than the other vessels.

Influencia del sistema nitridérgico en la respuesta contráctil a fenilefrina de anillos de vasos usados en revascularización coronaria

Endothelial dysfunction is associated to a lower production of nitric oxide and a reduction of endothelium mediated vasodilation.To study the effects of pharmacological agents that modify nitric oxide synthetase (NOS) activity on tension changes induced by phenylephrine in rings of internal mammary and radial arteries and saphenous vein.Vessel rings of 7 to 10 mm length were obtained from 32 patients subjected to coronary vascular surgery Fourteen samples of radial artery, 12 samples of internal mammary artery and 15 samples of saphenous vein were obtained. A maximal contraction was induced with KC1 and dose response curves for phenylephrine (FE) in the absence or presence of L-arginine and L-arginine methyl ester (L-NAME), were constructed.The tension induced by FE in internal mammary artery and saphenous vein reached a maximum, near 90% of 80 mM KCl-induced contraction, but in the radial artery, it reached a maximum of 63% (p <0.05). In all vessels, the dose response curves were significantly shifted to the right by L-arginine and to the left by L-NAME.Pre-incubation of human rings with L-ARG or L-NAME, changed the response to FE induced contraction, which may be related to different degrees of endothelial nitric oxide production or NO sensitivity. The basal NO production in radial artery seems to be larger than the other vessels.

Administration of a herbal immunoregulation mixture enhances some immune parameters in carp (Cyprinus carpio)

The herbal immunoregulation mixture (HIRM) were extracts of several traditional Chinese medicines (TCMs): Astragalus membranaceus (from the root and stem), Polygonum multiflorum Thunb. (from the root), Isatis tinctoria L. (from the root), Glycyrrhiza glabra (from the stem). Immune parameters, which included macrophage phagocytic activity, macrophage reactive oxygen species (ROS), activity of serum lysozyme, nitric oxide synthetase (NOS) and superoxide dismutase (SOD), levels of total serum protein, globulin, albumin, triglyceride and cholesterol, were determined in carp that had been fed diets containing HIRM at 0.5% or 1% for 30 days. The results showed that, compared with those in the control group, the diets with 0.5% and 1% HIRM resulted in significant increase in macrophage phagocytic activity, macrophage ROS and the levels of total protein, globulin, albumin and NOS activity in serum (P 0.05). On the other hand, 0.5% HIRM led to evident enhancement of NOS activity and cholesterol level compared to 1% HIRM. These results indicated that HIRM might elevate the function of immunity in carp (Cyprinus carpio).

VEGFR2 blockade in patients with solid tumors: Mechanism of hypertension and effects on vascular function

3037 Background: Hypertension is the most common side effect in trials with inhibitors of vascular endothelial growth factor (VEGF) signaling, although the underlying pathophysiology is unclear. As the use of anti-VEGF therapy is increasing, hypertension and related serious adverse events are likely to become more important. Methods: To better understand this pathophysiology,blood pressure and vascular function parameters were assessed in this substudy of a phase I trial in patients with advanced solid tumours treated with BAY 57–9352, an oral VEGF receptor 2 (VEGFR2) inhibitor. Blood pressure, flow-mediated dilatation (FMD), nitroglycerin-mediated dilatation (NMD) and pulse-wave velocity (PWV) were measured at baseline and after 5 weeks of daily treatment in 10 patients. Patients were spread out over different cohorts, taking different dosages of study drug. Results: Mean systolic blood pressure increased from 129.0 mm Hg to 139.4 mm Hg after 5 weeks of treatment (difference 10.4 mm Hg; 95% confidence interval (CI) 5.0–15.7 mm Hg; p=0.002). Mean diastolic blood pressure increased from 80.9 to 87.4 mm Hg (difference 6.5 mm Hg; 95% CI 1.7–11.3; p=0.013). Endothelium-dependent vasodilatation (FMD) decreased from 5.6% to 3.0% (95% CI 1.1–3.9%; p=0.003). NMD, indicating endothelium-independent vasodilatation, also decreased from 12.9% to 7.7% (95% CI 2.7–7.6%; p=0.001). Arterial stiffness (PWV), increased from 9.4 m/s to 10.3 m/s (p=0.07). Conclusions: Inhibition of VEGFR2 significantly increases systolic and diastolic blood pressure. As VEGF enhances endothelial nitric oxide (NO) synthetase activity, the clear decrease in FMD could be explained by reduced bioavailability of NO. The decrease in NMD may be a direct effect of VEGFR2 inhibition on vascular smooth muscle cells. However, a more likely hypothesis for these profound vascular effects is a reduced number of microvessels (i.e. rarefaction). As the microcirculation is largely responsible for peripheral resistance, the rarefaction associated with VEGFR2 inhibition is likely to increase peripheral resistance and lead to hypertension. [Table: see text]

EFFECT OF HE:NE LASER ON NEUTROPHILS PHAGOCYTIC ACTIVITY

The aim of this study is to investigate the effects exerted by He:Ne laser (632.8 nm) low level laser irradiation (LLLI) on neutrophil activity in response to op sonized zymosan. Human buffy coat leukocytes primed with opsonized zymosan were exposed to 10 mw He:Ne laser at energy densities of 1-5 J/cm 2 . Phagocytic activity was assessed by measuring percent of phagocytosis, H2O2 and nitric oxide (NO) generation together with neutrophil-associated nitric oxide synthetase activity (NOS) and Arginase I mRNA. LLLI stimulated neutrophil's phagocytic activity and free radicals generation. This effect was intensified, when neutrophils were dually stimulated by LLLI and opsonized zymosan within the dose range of 3-5 with maximum activity at 5 J/cm 2 .

Diet- and Colonization-Dependent Intestinal Dysfunction Predisposes to Necrotizing Enterocolitis in Preterm Pigs

Preterm birth and formula feeding are key risk factors associated with necrotizing enterocolitis (NEC) in infants, but little is known about intestinal conditions that predispose to disease. Thus, structural, functional, and microbiologic indices were used to investigate the etiology of spontaneous NEC development in preterm pigs. Piglets were delivered by cesarean section at 92% gestation, reared in infant incubators, and fed infant formula or colostrum every 3 hours (n = 120) until tissue collection at 1-2 days of age. Clinical and histopathologic signs of NEC were observed in 57% of pigs fed FORMULA (26/46) and in 5% of pigs fed COLOSTRUM (2/38) (P < .05). Relative to COLOSTRUM, both healthy and sick FORMULA pigs had reduced intestinal villous heights, enzyme activities, nutrient absorption, and antioxidant levels and higher inducible nitric oxide synthetase activity (P < .05). In healthy pigs, mucosal microbial diversity remained low and diet independent. NEC pigs showed bacterial overgrowth, and a high mucosal density of Clostridium perfringens was detected in some but not all pigs. Germ-free conditions and antiserum against Clostridium perfringens toxin prevented intestinal dysfunction and NEC in formula-fed pigs, whereas the gut trophic factors, epidermal growth factor, and glucagon-like peptide 2 had limited effects. A subclinical, formula-induced mucosal atrophy and dysfunction predispose to NEC and bacterial overgrowth. The adverse feeding effects are colonization dependent and may be reduced by factors in colostrum that include antibodies against aggressive toxins such as those of Clostridium perfringens.

Safrole oxide induced human umbilical vein vascular endothelial cell differentiation into neuron-like cells by depressing the reactive oxygen species level at the low concentration

Previously, we found that 5–25 μg/ml safrole oxide could inhibit apoptosis and dramatically make a morphological change in human umbilical vein vascular endothelial cells (HUVECs). But the possible mechanism by which safrole oxide function is unknown. To answer this question, in this study, we first investigated the effects of it on the activity of nitric oxide synthetase (NOS), the expressions of Fas and integrin β4, which play important roles in HUVEC growth and apoptosis, respectively. The results showed that, at the low concentration (10 μg/ml), safrole oxide had no effects on NOS activity and the expressions of Fas and integrin β4. Then, we investigated whether HUVECs underwent differentiation. We examined the expressions of neuron-specific enolase (NSE) and neurofilament-L (NF-L). Furthermore, we analyzed the changes of intracellular reactive oxygen species (ROS). After 10 h of treatment with 10 μg/ml safrole oxide, some HUVECs became neuron-like cells in morphology, and intensively displayed positive NSE and NF-L. Simultaneously, ROS levels dramatically decreased during HUVECs differentiation towards neuron-like cells. At the low concentration, safrole oxide induced HUVECs differentiation into neuron-like cells. Furthermore, our data suggested that safrole oxide might perform this function by depressing intracellular ROS levels instead of by affecting cell growth or apoptosis signal pathways.

The effects of selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib, on experimental colitis induced by acetic acid in rats

Several mediators may be involved in the pathogenesis of inflammatory bowel disease, as well as in experimental colitis. The present work was conducted to investigate the effects of the two selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib, on experimentally induced colitis in rats. Rectal instillation of acetic acid was used to induce the colitis. Acetic acid treatment caused haemorrhagic diarrhoea and weight loss in rats. Celecoxib (5 mg/kg) or rofecoxib (2.5 mg/kg), when given twice daily by the oral route, reduced the degree of haemorrhagic diarrhoea and the weight loss produced. In addition, they produced a significant reduction in the degree of colonic injury, the rise in myeloperoxidase (MPO) levels, total nitric oxide synthetase (NOS) activity, platelet-activating factor (PAF), histamine levels and prostaglandin E 2 levels. In contrast, there was a significant increase in the levels of reduced glutathione (GSH). Thus, the findings of the present study provide evidence that selective cyclooxygenase-2 inhibitors may be beneficial in patients with inflammatory bowel disease.

Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats

Ulcerative colitis is a common inflammatory bowel disease (IBD) of unknown etiology. Recent studies have revealed the role of some microorganisms in the initiation and perpetuation of IBD. The role of antibiotics in the possible modulation of colon inflammation is still uncertain. In this study, we evaluated the effects of two macrolides, namely azithromycin and erythromycin, at different doses on the extent and severity of ulcerative colitis caused by intracolonic administration of 3% acetic acid in rats. The lesions and the inflammatory response were assessed by histology and measurement of myeloperoxidase (MPO) activity, nitric oxide synthetase (NOS) and tumor necrosis factor alpha (TNFα) in colonic tissues. Inflammation following acetic acid instillation was characterized by oedema, diffuse inflammatory cell infiltration and necrosis. Increase in MPO, NOS and TNFα was detected in the colonic tissues. Administration of either azithromycin or erythromycin at different dosage (10, 20 and 40 mg/kg orally, daily for 5 consecutive days) significantly ( P < 0.05) reduced the colonic damage, MPO and NOS activities as well as TNFα level. This reduction was highly significant with azithromycin when given at a dose of 40 mg/kg. It is concluded that azithromycin and erythromycin may have a beneficial therapeutic role in ulcerative colitis.

Legionella pneumophila Infection Possibly Related to Treatment With Infliximab

Legionella pneumophila Infection Possibly Related to Treatment With Infliximab