Mohammed A. Alzoghaibi

Concepts of oxidative stress and antioxidant defense in Crohn’s disease

Oxygen free radical and lipid peroxides (oxidative stress) are highly reactive and represent very damaging compounds. Oxidative stress could be a major contributing factor to the tissue injury and fibrosis that characterize Crohns disease. An imbalance between increased reactive oxygen species levels and decreased antioxidant defenses occurs in Crohns patients. Decreased blood levels of vitamins C and E and decreased intestinal mucosal levels of CuZn superoxide dismutase, glutathione, vitamin A, C, E, and β-carotene have been reported for Crohns patients. Increased levels of proinflammatory cytokines, such as interleukin-1 and -8 and tumor necrosis factor, have been detected in inflammatory bowel disease. Oxidative stress significantly increased the production of neutrophils, chemokines, and interleukin-8. These effects were inhibited by antioxidant vitamins and arachidonic acid metabolite inhibitors in human intestinal smooth muscle cells isolated from the bowels of Crohns disease patients. The main pathological feature of Crohns disease is an infiltration of polymorphonuclear neutrophils and mononuclear cells into the affected part of the intestine. Activated neutrophils produce noxious substances that cause inflammation and tissue injury. Due to the physiological and biochemical actions of reactive oxygen species and lipid peroxides, many of the clinical and pathophysiological features of Crohns disease might be explained by an imbalance of increased reactive oxygen species and a net decrease of antioxidant molecules. This review describes the general concepts of free radical, lipid peroxide and antioxidant activities and eventually illustrates their interferences in the development of Crohns strictures.

Neutrophil expression and infiltration into Crohn's intestine

Crohns disease (CD) is a chronic inflammatory bowel disease (IBD) of unknown etiology. The main pathological feature of IBD is transmural infiltration of polymorphonuclear neutrophils (PMN) and mononuclear cells associated with smooth muscle cell proliferation, accumulation of collagen, thickening and stenosis. While the etiology of Crohns disease remains unknown, increased levels of proinflammatory cytokines, such as IL-1, IL-6, IL-8 and TNF in the inflamed bowel probably play a major role in the tissue injury and fibrosis that ensue. PMNs infiltrate into tissue in response to chemotactic signals produced by the tissue, such as a-chemokines (IL-8). Although, the initial infiltration of neutrophils is beneficial to kill foreign particles and bacteria, persistent infiltration causes tissue damage. This review shows some evidence of neutrophil expression in Crohns bowel and the process of neutrophil infiltration into the inflamed tissue.

Diurnal Intermittent Fasting during Ramadan: The Effects on Leptin and Ghrelin Levels

We aimed to assess the effect of Islamic intermittent fasting, during and outside of Ramadan, on plasma levels of leptin and ghrelin while controlling for several potential confounding variables. Eight healthy male volunteers with a mean age of 26.6±4.9 years reported to the sleep disorders center (SDC) at King Saud University on four occasions: 1) adaptation; 2) 4 weeks before Ramadan while performing Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting. Plasma leptin and ghrelin levels were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. During BLF, there were significant reductions in plasma leptin concentrations at 22:00 and 02:00 compared with the baseline concentrations (at 22:00: 194.2±177.2 vs. 146.7±174.5; at 02:00: 203.8±189.5 vs. 168.1±178.1; p<0.05). During Ramadan, there was a significant reduction in plasma leptin levels at 22:00 (194.2±177.2 vs. 132.6±130.4, p<0.05). No significant difference in plasma ghrelin concentrations was detected during the BL, BLF, or Ramadan periods. Cosinor analyses of leptin and ghrelin plasma levels revealed no significant changes in the acrophases of the hormones during the three periods. The nocturnal reduction in plasma leptin levels during fasting may be the result of the changes in meal times during fasting.

Lipid peroxides in patients with inflammatory bowel disease

BACKGROUND/AIMS In this study, we aimed to determine the levels of malondialdehyde (MDA) in patients with inflammatory bowel disease (IBD) to investigate its contribution to tissue injury in IBD. MATERIALS AND METHODS Forty-two patients with IBD (24 cases of Crohns disease and 18 cases of ulcerative colitis) and 38 matched healthy subjects (control group) were considered for study. MDA levels were quantified by the measurement of thiobarbituric acid reactive substances. RESULTS Plasma MDA levels of Crohns disease patients were significantly higher than the control group, but not higher than the ulcerative colitis patients. Plasma MDA levels of patients with ulcerative colitis were higher than the control group but not significant. CONCLUSION Increased levels of plasma MDA in IBD is an important indication of oxidative stress. Patients with Crohns disease are more susceptible to oxidative stress than patients with ulcerative colitis.

Lipid peroxides in stable asthmatics receiving inhaled steroids and long-acting β2-agonists

Background and objective:  The effect of inhaled steroids on oxidative stress in asthmatics is unclear. The levels of lipid peroxides in the serum of asthmatic patients, whose symptoms were controlled with inhaled corticosteroids and long‐acting β2‐agonists, were measured in this study.

Circulating LTB4 and Eotaxin-1 in stable asthmatics on inhaled corticosteroids and long-acting β 2-agonists

BACKGROUND : Leukotrienes B4 (LTB4) and eotaxin-1 are thought to play a pivotal role in the pathogenesis of asthma. This study investigates the plasma levels of LTB4 and eotaxin-1 in symptom-free asthmatics on inhaled corticosteroids (ICS) and long-acting β2 (LABA) . MATERIALS AND METHODS : Twenty asthmatic patients treated with ICS and LABA for 3 months and 17 matched healthy subjects were recruited. LTB4 and eotaxin-1 were measured in the serum by a specific enzyme immunoassay kit. RESULTS : Treatment resulted in significant improvement in FEV1 and disappearance of symptoms. LTB4 levels were significantly lower in the treated asthmatics compared to the healthy subjects (19.17 ± 0.8 pg/ml versus 23.34 ± 0.82 pg/ml respectively, P CONCLUSION : Asthmatics treated with ICS and LABA showed significantly lower levels of LTB4 compared to healthy subjects. Regular use of inhaled corticosteroids and long-acting β2 may help in controlling the inflammatory process in asthma. Further studies are needed to confirm these findings and assess the association between clinical and physiological parameters and circulating chemokines and cytokines.

Factors regulating the renal circulation in spontaneously hypertensive rats

Hypertension is one of the leading causes of health morbidity and mortality which are linked to many life threatening diseases such as stroke heart problems and renal dysfunction. The integrity of renal microcirculation is crucial to maintaining the clearance and the excretory function in the normotensive and hypertensive conditions. Furthermore, any alteration in the renal function is involved in the pathophysiology of hypertension. The aim of this review is to provide a brief discussion of some factors that regulate renal haemodynamics in spontaneously hypertensive rats, an animal model of hypertension, and how these factors are linked to the disease.

Upregulation of the proinflammatory cytokine-induced neutrophil chemoattractant-1 and monocyte chemoattractant protein-1 in rats' intestinal anastomotic wound healing—Does it matter?

BACKGROUND The proinflammatory cytokines and growth-promoting factor are essential components of the wound healing process. We hypothesized that under healthy conditions, faster healing of intestinal anastomotic wound is due to an early upregulation of proinflammatory cytokines, cytokine-induced neutrophil chemoattractant-1 (CINC-1) that is followed by a quicker upregulation of homeostatic chemokine, monocyte chemoattractant protein-1 (MCP-1) and late upregulation of transforming growth factor (TGF-β). METHODS We characterized the time course of CINC-1, MCP-1 and TGF-β release at four wounds (skin, muscle, small bowel, and colonic anastomosis) after surgery on 38 juvenile male Sprague Dawley rats. The tissue samples of each site were harvested at 0 (control), 1, 3, 5, 7 and 14 days postoperatively (n = 6-8/group) and analyzed by ELISA kits for CINC-1, MCP-1 and TGF-β. RESULTS CINC-1 expression peaked earlier in muscle and colonic wounds when compared to skin and small bowel. MCP-1 levels were elevated early in skin and muscle wounds, but later expression of MCP-1 was shown in colonic wounds. TGF-β levels were unchanged in all wound sites. CONCLUSION An earlier peak in CINC-1 levels and later expression of MCP-1 were seen in colonic wounds, but no significant increase in TGF-β levels was observed. These findings support the early healing process in intestinal anastomotic wounds.

The effect of Ramadan intermittent fasting on lipid peroxidation in healthy young men while controlling for diet and sleep: A pilot study

Aims: We hypothesized that if we control for lifestyle changes during Ramadan, Ramadan Islamic intermittent fasting (IF) reduces oxidative stress. This study was conducted to examine the effect of Islamic IF during and outside of Ramadan on the circadian changes in lipid peroxidation marker malondialdehyde (MDA) during and outside while controlling for potential confounders. Methods: Serum MDA concentration was measured in eight healthy male volunteers at baseline (BL), after fasting for 1 week before Ramadan (BL fasting), and during Ramadan. Blood samples were drawn at 22:00, 02:00, 04:00, 06:00, and 11:00. The participants were admitted to the sleep laboratory and monitored for 24 h on the day of the measurements. In the laboratory, each participant received meals of fixed compositions and caloric contents based on their ideal body weights. Light exposure, physical activity, and total sleep duration were uniformly maintained during the three study periods. Results: The participants had a mean age of 26.6 ± 4.9 years and a mean body mass index of 23.7 ± 3.5 kg/m2. No significant changes were observed in MDA levels and blood glucose during BL, BL fasting, or Ramadan. Conclusion: In this pilot study, under conditions of fixed sleep-wake schedules and caloric intake, Ramadan IF does not alter serum MDA levels in healthy subjects. Larger studies are needed to confirm these findings.

The time course of cytokine expressions plays a determining role in faster healing of intestinal and colonic anastomatic wounds

Objectives: Inflammation is critical in the early phases of wound healing. It has been reported previously that small intestinal and colonic wounds display a more rapid healing than those of other organs. However, the underlying mechanism has not yet been elucidated. Here we examined whether differences in the time course of specified cytokine expression, in colonic and small intestinal anastomotic lesions, might play a major role in this observation in comparison to lesions effecting skin and muscle tissue. Materials and Methods: Tissue lesions were applied to 36 male Sprague–Dawley rats. Tissue samples were harvested at 1, 3, 5, 7, and 14 days postoperatively with the levels of TNF-α, IL-6, and IFN-α determined by ELISA-derived methods. Results: The characteristics of TNF-α, IL-6, and IFN-α expression during the healing process for intestinal and colonic lesions were comparable. However, data differed significantly with that observed during healing of skin and muscle lesions. Intestinal and colonic lesions exhibited a significant and sustained increase in specified cytokine levels on day 5 to day 14 as compared with day 1 and 3. Skin and muscle lesions had random or unaltered cytokine levels throughout the study period. Conclusion: Differences in expression of cytokines TNF-α, IL-6, and IFN-α indicate that these play an important role underlying the more rapid healing processes observed in small intestinal and colonic lesions.