Mild Inflammatory Disease Research Articles

Vitamin C Physiology: The Known and the Unknown in Obesity

Vitamin C is effective in strengthening the immune system, capillary blood vessels and protecting the dental health, as well as in the convenient use of iron, calcium, thiamine, riboflavin, folic acid, vitamin A and E in the body. Vitamin C also acts as a cofactor for 15 different enzymes, and shows antioxidant activity as a electron donor reducing agent. It acts as a powerful free radical scavenger by protecting tissues against oxidative stress and reduces inflammation. Obesity is defined as “mild inflammatory disease” due to the increase in inflammatory markers such as C reactive protein (CRP), tumor necrosis factor alpha (TNF) and IL-6. Since antioxidant enzyme activity and serum antioxidant levels decrease in obese individuals, the effect of antioxidant vitamins on weight loss is further investigated. In studies investigating the effectiveness of vitamin C in the treatment of obesity; vitamin C was found to reduce systemic inflammation by inhibiting CRP and TNF alpha pathways, shown to inhibit the hypoxia in adipose tissue with potential for protection against free radicals and decreasing lipid peroxidation. On the other hand, it was shown that vitamin C inhibits mature adipocyte formation and cell growth, inhibits lipolysis, and can be considered as a treatment model for obesity to offer solutions for abnormal fat accumulation. In this review, the action mechanism of vitamin C and its role in dietary treatment were investigated in order to prevent obesity complications and to provide weight loss.

The ssDNA exonucleases PLD3 and PLD4 are required to prevent lethal primary HLH-like disease in mice

Abstract Leukocyte sensing of microbial genetic material often elicits beneficial proinflammatory cytokines, but dysregulated responses can cause severe pathogenesis. Genome-wide association studies have linked Phospholipase D3 (PLD3) to Alzheimer’s disease and PLD4 to rheumatoid arthritis and systemic sclerosis. PLD3 and PLD4 are endolysosomal proteins with no detectable phospholipase activity. PLD4 deficient mice have a mild inflammatory disease, marked by elevated interferon-γ (IFN γ) and splenomegaly. These phenotypes were traced to an altered responsiveness of PLD4-deficient dendritic cells to ligands of the single-stranded DNA (ssDNA) sensor Toll-like receptor 9 (TLR9). Thioglycolate elicited peritoneal macrophages from PLD3-deficient mice also had exaggerated TLR9 responses to particular ligands. Although PLD4 and PLD3 were presumed to be phospholipases, we found that they are 5′-ssDNA exonucleases that break down TLR9 ligands. Mice deficient in both PLD3 and PLD4 died pre-weaning from an inflammatory disease with many similarities to primary hemophagocytic lymphohistiocytosis (HLH). The levels of IFN γ, IL-6, TNF α, IL-10 and ferritin were markedly elevated in the serum of Pld3−/−Pld4−/− mice. Low blood platelets, severe anemia, liver steatosis, and hemophagocytosis were evident in Pld3−/−Pld4−/− mice. The lethal inflammation in PLD3 and PLD4 deficient animals was only marginally improved by IFN γ deficiency, however inactivation of UNC93B1 rescues their survival, revealing excessive endosomal TLR signaling is responsible for driving the disease.

The Effect of Resistance Training with Theraband on the Transforming Growth Factor-β in the Elderly Women

Background: Ageing and physical inactivity can negatively affect immune system. On the contrary, a healthy lifestyle and physical activity can improve immune system and prevent from mild inflammatory diseases. Transforming Growth Factor-β (TGF-β) can play an important role in the regulation of immune function and inflammation. This study aimed to investigate the effects of 8 weeks of theraband resistance training on the plasma level of TGF-β in the elderly women. Materials and Methods: Eighteen inactive elderly women were selected and randomly assigned to either theraband (n=10) and control (n=8) groups. The theraband group attended 24 exercise sessions conducted over an 8-week period (3 sessions/week). Exercise load was increased according to the color of theraband. The TGF-β level in plasma was measured by ELISA. Results: Mean±SD plasma level of TGF-β in the theraband group (39.42±9.46) significantly decreased compared to that in the control group (64.26±21.39) (P=0.031).Conclusion: The results showed that lower level of TGF-β and improvement of immune system following resistance training may (at least partially) protect the elderly women against infectious and inflammatory diseases.

Inflammatory bowel disease in India—changing paradigms

Inflammatory bowel disease is an emerging problem in Asia including India. Clinical data on this disease from eastern India and on its temporal trends in India is scarce. Existing Indian data on inflammatory bowel disease were retrieved using PubMed and a comparison of earlier data (up to 1980s) was made with more recent data (1990s and later) and our own data to find any significant differences. Our data included clinical data of 40 and ten consecutive patients with ulcerative colitis and Crohn's disease, respectively, collected prospectively from January 2003 to June 2009. For those whose symptoms started before 2003, data collection was partly retrospective. It included demography, symptoms and duration at presentation, follow-up findings, course, extraintestinal manifestations, treatment outcome and complications. Data were analysed by descriptive and analytical statistics. Sixty-five percent of our ulcerative colitis patients presented with pancolitis, majority had severe clinical, endoscopic and histologic disease commensurate with other recent studies but in contrast to milder presentation in earlier studies. Of our patients, 27.5% developed pseudopolyposis of colon, two within 1year of disease onset; 10% developed cancer colon for whom disease duration of 10years or more was the only significant risk factor. Majority of our patients with Crohn's disease had mild inflammatory disease involving small gut which was controlled with aminosalicylates. Obscure lower GI bleed was an important mode of presentation. Ulcerative colitis is presenting with increasing severity and extent in recent times. Rapid development of colonic pseudopolyposis was observed.

Vasoactive intestinal peptide impairs leucocyte migration but fails to modify experimental murine colitis

Inflammatory bowel diseases are chronic inflammatory disorders of the gastrointestinal tract. Vasoactive intestinal peptide (VIP) is a neuropeptide with known anti-inflammatory activity. We have demonstrated previously that administration of VIP inhibits leucocyte migration in a murine model of delayed-type hypersensitivity, and anti-inflammatory efficacy is supported by other studies. The aim of this study was to investigate the VIP effects in a murine model of intestinal inflammation. Colitis was induced in BALB/c mice by a 2.5 mg enema of 2,4,6-trinitrobenzenesulphonic acid (TNBS) and the mice were killed on day 7. Mice were administered either a 3-day (therapeutic) or 7-day (prophylactic) constant infusion of VIP by subcutaneously implanted mini-osmotic pumps, or intraperitoneal (i.p.) injection of VIP on alternate days over 7 days. Clinical disease scores, weight changes, histopathology of colon tissues, plasma VIP levels, cytokine levels and chemotaxis of peripheral blood mononuclear cells were evaluated. After administration of TNBS, mice quickly developed severe colitis accompanied by dramatic body weight loss (20% by day 6) and high mortality (30%). Prophylactic treatment using high-dose VIP abrogated leucocyte chemotaxis; however, it failed to ameliorate the weight loss and mortality. Moreover, VIP delivered either by constant infusion or i.p. failed to modify the clinical, histological or cytokine markers of disease. Our studies show that, despite an ability to inhibit chemokine-induced chemotaxis of mononuclear cells, VIP was unable to modulate TNBS-induced colitis. This contrasts with the efficacy of VIP in models of mild inflammatory disease and suggests that VIP is unlikely to provide a useful model for novel anti-IBD therapy.

Primary angiitis of the central nervous system: report of five biopsy-confirmed cases from Colombia

Introduction Primary (isolated) angiitis of the central nervous system (PACNS) is a rare cause of cerebrovascular disease (CVD), and few leptomeningeal and brain biopsy (LBB)-confirmed cases have been reported from South America. Methods We retrospectively reviewed charts of patients with diagnosis of cerebral angiitis admitted between March 1991 and July 2001 to a single university hospital in Medellin, Colombia. Patients with definitive diagnosis of PACNS by Alrawi et al.'s [A. Alrawi, J.D. Trobe, M. Blaivas, D.C. Musch, Brain biopsy in primary angiitis of the central nervous system. Neurology, 53 (1999), 858-860] LBB criteria were selected. We excluded other causes of cerebral angiitis as well as cases without LBB confirmation. Results We report five patients, four men and one woman, with a mean age at onset of 24.4 years, and an average disease progression of 12.4 days. Four presented with headache and motor weakness, three had seizures, and two had alterations of consciousness. Cerebral MRI was abnormal in all five cases; brain CT in four, and cerebral angiography in two. The cerebrospinal fluid (CSF) was abnormal in two patients. Leptomeningeal and brain biopsies revealed mononuclear infiltration in the wall of small blood vessels in all. Three had concurrent meningeal and cerebral involvement, two had necrotizing angiitis, and one had vascular and encephalitic lesions. All received only steroid treatment; the 1-year follow-up revealed good prognosis without relapses. Conclusion We report five biopsy-proven cases of PACNS from Colombia associated with neurological and neuroimaging abnormalities; these patients presented a mild inflammatory disease that was correlated with few CSF abnormalities and good response to single steroid treatment without relapses. Leptomeningeal and brain biopsy is mandatory for a definitive diagnosis.