Stone O.J.
18700 Main Street, Huntington Beach, CA 92646 USA
Med. Hypotheses (United Kingdom), 1990, 31/2 (99-103)

Shortly after the introduction of sulfa drugs, sulfapyridine was found tohave unique therapeutic properties, unrelated to antibacterial activity. Later, sulfones were found to share the same properties. The disorders initially improved were dermatitis herpetiformis, pyoderma gangrenosum, subcorneal pustular dermatosis, acrodermatitis continua, impetigo herpetiformis and ulcerative colitis. They were also sometimes helpful in many other disorders. They are effective in select disorders characterized by edema followed by granulocytic inflammation or edema followed by vesicle or bullae formation. The sulfones work in low doses in leprosy and their mode of action is not fully understood. Several pieces of experimental information are available. It is proposed that these drugs are entering or influencing the protein moiety of glycosaminoglycans and decreasing tissue viscosity. This decreased tissue viscosity prevents edema and dilution of tissue fluid and decreases acute inflammation and vesicle and bullae formation.

Symonds D.A.
Dept. Pathol., US Publ. Hlth Serv. Hosp., Baltimore, Md. USA
Arch. Pathol. Lab. Med. (USA), 1978, 102/3 (146-149)

The glycosaminoglycans from normal colonic mucosa and colons with avariety of inflammatory diseases, as well as benign and malignant neoplasms were analyzed. Normal colonic mucosa contains predominantly chondroitin sulfates and dermatan sulfate. Increases in the levels of hyaluronic acid and heparan sulfate, as well as substantial increases in the amount of total glycosaminoglycans were characteristic of invasive colonic adenocarcinoma. Lesser elevations in the amount of total glycosaminoglycans and hyaluronic acid and heparan sulfate were present in neonatal colonic mucosa, villous adenoma, ulcerative colitis, and mucosa adjacent to carcinoma. The degree of elevation was proportional to the dysplastic potential. Since dysplastic lesions have scant connective tissue, the epithelial component of colonic neoplasms may contribute to these neoplasm-related alterations in glycosaminoglycan composition.

Siegel J.
7410 Long Point Rd, Houston, Tex., 77055 USA
Ann. Allergy (USA), 1981, 47/2 (92-94)

That inflammatory bowel disease (IBD) is just another possible facet of allergy is shown by the alleviation of IBD following allergy testing and treatment. This is further borne out by the findings in a survey (questionnaire) of local members of the National Foundation of Ileitis and Colitis (NFIC) in which 70% of individuals with IBD listed other symptoms which were judged to be 'Possibly Allergic.'

Aitola P.T.; Soppi E.T.; Halonen P.J.; Laine S.T.; Matikainen M.J.
Dept. of Surgery, Tampere University Hospital, P.O. Box 2000, FIN-33521 Tampere Finland
Scand. J. Gastroenterol. (Norway), 1994, 29/7 (646-650)

Background: The levels of antibodies against cow's milk proteins inulcerative colitis (UC) were used to study whether mucosal inflammation leads to immune recognition, as a marker of enhanced permeability, of dietary proteins. A further purpose was to study the effect of proctocolectomy on the serum antibody levels against cow's milk proteins and their relation to biochemical and histologic liver abnormalities associated with ulcerative colitis.

Methods: Serum antibody levels against six cow's milk proteins, alpha-casein, alpha-lactalbumin (LA), beta-lactoglobulin A (LGA), beta-lactoglobulin B (LGB), bovine serum albumin (BSA), and whole milk powder (MP) were determined before and after (mean, 24 months) proctocolectomy in 125 patients with ulcerative colitis. Simultaneously, serum liver enzymes were analyzed. A liver biopsy specimen was also obtained at proctocolectomy.

Results: Before proctocolectomy IgA antibody levels were significantly increased against all antigens except BSA. Increased levels of IgM antibodies against LGA, LGB, and BSA were also detected. IgG antibodies were significantly increased only against LGA. After proctocolectomy IgA and IgM antibody levels decreased significantly (p < 0.05) against LGA, LGB, and LA, whereas IgG antibodies increased significantly (p < 0.01). In the patient group with abnormal liver histology (n = 9) the IgA antibodies to all cow's milk proteins were significantly higher (p < 0.02) than in the group with normal liver histology both before and after proctocolectomy. The IgA antibody levels showed a significant positive correlation with alanine amino-transferase and gamma-glutamyltransferase (r value from 0.460 to 0.721, p value from < 0.05 to < 0.01), but not with alkaline phosphatase.

Conclusions: These results suggest that the inflamed mucosa in UC allows the antigenic contents of the bowel to escape. Proctocolectomy alters the antibody levels against certain milk proteins, which may serve as a model to suggest that proctocolectomy, probably by eliminating inflammation, may have positive effects by reducing the foreign pathogenic antigen and immune complex load.

Paganelli R.; Pallone F.; Montano S.; et al.
Cattedra di Immunologia Clinica, Clinica Medica III, Policlinico Umberto I, I-00161 Roma Italy
Int. Arch. Allergy Appl. Immunol. (Switzerland), 1985, 78/1 (81-85)

We studied the class-specific antibody response to the cow's milk antigenbeta-lactoglobulin (beta-LG) in sera from patients with ulcerative colitis and Crohn's disease. IgG and IgM to beta-LG were significantly higher in patients when compared to healthy non-atopic controls, whereas IgA values were similar, and specific IgE absent in all groups. No correlation between IgG- and IgM-containing immune complexes was found with the corresponding isotype of antibody to beta-LG; however, IgM complexes correlated with serum total IgM in ulcerative colitis. In these patients, IgG antibodies were higher in active cases, whereas IgM increased in patients without signs of disease activity. Antibody titers did not correlate with disease duration or administration of antiinflammatory drugs. This pattern of anti-beta-LG reactivity suggests that the presence of intestinal lesions may be revealed by the selective increase of some antibody isotopes to orally administered antigens. Enhanced mucosal permeability may be studied by this type of serological analysis.

Prudden J.F.; Balassa L.L.
Dept. Surg., Coll. Phys. Surg., Columbia Univ., New York, N.Y. USA
Semin.Arthritis Rheum. (USA), 1974, 3/4 (287-321)

Catrix is a material with proven clinical safety and efficacy in thetreatment of important chronic inflammatory conditions. Among these entities the authors have had the most experience with osteoarthritis, psoriasis, anal and perianal conditions, and inflammatory bowel disease. The results in the rheumatic diseases, while still preliminary, are encouraging and deserve intensive further investigation. An expansion of these studies should provide important new information about the nature and treatment of many diseases for which there is no present nontoxic therapy of value.

Mielants H.; Veys E.M.
Department of Rheumatology, University of Ghent, B-9000 Ghent Belgium
J. Rheumatol. (Canada), 1985, 12/2 (287-293)

In an open study, sulfasalazine was given to 15 HLA-B27 positive patientswith asymmetrical pauciarticular arthritis and enthesopathies resistant tononsteroidal antiinflammatory drugs (NSAID). In 11 patients, long lasting remission of inflammatory and biological variables was obtained after 3 to 12 months of treatment. In the other 4 patients significant improvement of the clinical and biological variables was observed. In the 7 patients on whom ileocolonoscopy was performed, inflammatory signs were seen in the terminal ileum or ileococcal valve, suggestive of inflammatory bowel disease (IBD). It is generally accepted that sulfasalazine improves the intestinal symptoms of IBD; our study suggests that it is also beneficial in HLA-B27 related arthropathies resistant to NSAID. No significant adverse reactions were encountered. These findings are encouraging but have to be confirmed in a double blind controlled study.

Mielants H.; Veys E.M.; Cuvelier C.; et al.
Department of Rheumatology, University of Ghent, B-9000 Ghent Belgium
J. Rheumatol. (Canada), 1985, 12/2 (294-298)

Ileocolonoscopy and microscopic examination of ileum biopsies wereperformed on 35 patients with reactive arthritis, with asymmetricalpauciarticular arthritis and enthesopathies. Ileocolonoscopy was alsoperformed on 26 patients with ankylosing spondylitis (AS) and on 19 control patients with rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus and psoriatic arthritis. In the reactive group, ileocolonoscopy showed macroscopic inflammation in 16 cases and abnormal microscopic examination in all but 2 cases, even in patients without gastrointestinal disorders. In the 2 patients with sexually acquired disease, the gut was normal. In the AS group, inflammation was observed in the B27 negative and positive patients with peripheral joint involvement. Occasionally, ileal signs were seen in the HLA-B27 positive patients without peripheral joint involvement. None of the controls showed signs of gut inflammation. Ileocolonoscopy may be of value in detecting subclinical forms of bowel inflammation.

Ramakrishna B.S.; Varghese R.; Jayakumar S.; Mathan M.; Balasubramanian K.A.
Dr. B.S. Ramakrishna, Dept. of Gastrointestinal Sciences, Christian Medical College Hospital, Vellore 632004 India
Journal of Gastroenterology and Hepatology (Australia), 1997, 12/7 (490-494)

Oxygen free radicals produced by neutrophils are important in thepathogenesis of mucosal damage in ulcerative colitis. Vitamin A, vitamin E and cysteine in the plasma can scavenge free radicals. In the present study, plasma levels of vitamin A, vitamin E, cysteine, cystine and protein-bound cysteine were measured in active ulcerative colitis before and immediately after treatment of the active disease, and correlated with disease severity, extent and activity. Plasma vitamin A and cysteine were significantly reduced in active ulcerative colitis compared with controls. Levels of vitamin E, cystine and protein-bound cysteine were not significantly altered in active ulcerative colitis. Vitamin A and cysteine concentrations returned to normal levels (P< 0.05) within 2 weeks of treating active colitis. There were significant negative correlations between clinical severity and the plasma concentrations of vitamin A and cysteine. Plasma cysteine levels also correlated inversely to disease extent. Depletion of the circulating antioxidants, vitamin A and cysteine, in active ulcerative colitis is likely to be important in the pathophysiology of the disease.

Wasser T.E.; Reed J.F.; Moser K.; Robson P.; Faust L.; Fink L.L.; Wunderler D.
Research Department, The Lehigh Valley Hospital, Cedar Crest and I-78, Allentown, PA 18105-1556 USA
Canadian Journal of Gastroenterology (Canada), 1995, 9/3 (131-136)

Using the Harvard/Willett Semi-Quantitative Food Frequency Questionnaire (H/WSQFFQ), nutritional information was gathered on patients enrolled in an inflammatory bowel disease (IBD) registry. The registry lists 320 patients positive for either ulcerative colitis (n = 124) or Crohn's disease (n = 196). The sample was limited to those 19 to 84 years old (meanplus or minusSD 48.57plus or minus14.98), and comprised 136 males and 184 females. Using a battery of indices, quality of life, disease activity and general well-being were also assessed. Nutritional intake values from the Harvard-Willett data were compared with recommended dietary allowances (RDA) tables by sex age group (19 to 24 years, 25 to 50, 51 and older) to discover any intake deficiencies. Results showed that IBD patients were below RDA guidelines for vitamin E, calcium, magnesium, zinc iodine and selenium. Females were below RDA guildelines for iron while men were below for vitamin B6. There were also some deficiencies according to age in males and two nutrient deficiencies were seen by age group in women. There were no deficiencies by sex or age for vitamins A, C, D and niacin. There were no observed nutrient intake differences between ulcerative colitis and Crohn's disease groups. Patients receiving vitamin or mineral supplementation showed significant decreases in quality of life, regardless of diagnosis (Crohn's disease or ulcerative colitis) group. The H/WSQFFQ is a useful tool for assessment of the nutritional status of the IBD patient because it not only provides valuable measurement data to the clinician, but also adds to patient awareness about nutritional problems associated with IBD.

Cetiner S.; Gorgulu S.; Kaymakcioglu N.; Sen D.
Genel Cerrahi Anabilim Dali, GATA, 06018 Etlik, Ankara Turkey
Bulletin of Gulhane Military Medical Academy (Turkey), 1994, 36/4 (452-457)

One of mediators which have been implicated as the cause of tissue injury in ulcerative colitis is the free oxygen radicals. In this study, it is investigated to induce experimental ulcerative colitis in this group. Vitamin E was administered IP at the same time with, before, before and after Mitomycin C in groups 3, 4 and 5 respectively. In group 2 than group 1, it was observed significantly meaningful histopathological alterations in colonic mucosa and meaningful decrease superoxide dismutase (SOD) levels in plasma (p < 0.01). While meaningful histopathological alterations in colonic mucosa were observed in groups 3 and 5 than group 1 (p < 0.05), but it is not as severe as group 2 and there was not meaningful difference SOD levels in plasma (p < 0.05). In group 4, histopathological alterations in colonic mucosa which were not as severe as group 2, but more severe than groups 3 and 5 and meaningful decrease SOD levels in plasma were observed (p > 0.05). As a result, free oxygen radicals are effective in the pathogenesis of experimental ulcerative colitis. Vitamin E, an antioxidant agent, appears to be a good choice in the treatment of the experimental ulcerative colitis.

Lauritsen K.; Laursen L.S.; Bukhave K.; Rask-Madsen J.
Department of Medical Gastroenterology, Odense University Hospital, Odense, DK-5000 Odense C Denmark
Pharmacol. Toxicol. (Denmark), 1987, 61/4 (246-249)

To determine whether supplementation with the physiological radical scavenger, vitamin E, would modulate arachidonate metabolism in human inflammation, we performed equilibrium dialysis of rectum in eight patients with active ulcerative colitis confined to the rectum. The patients, all off drug treatment, were supplemented with 1920 IU/day of alpha-tocopherol and had rectal dialysis done at entry and after three and 14 days. Luminal concentrations of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), determined by radioimmunoassay in purified dialysates, were significantly raised compared to healthy controls. Supplements caused no change in these levels either at day 4 or 15, although serum-tocopherol showed a 3-fold increase. Also disease activity was unaffected. This failure of vitamin E supplementation to suppress the mucosal release of PGE2 and LTB4 in active inflammation does not encourage controlled trials of the effect of oral vitamin E in ulcerative colitis.

Krasinski S.D.; Russell R.M.; Furie B.C.; et al.
USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111 USA
Am. J. Clin. Nutr. (USA), 1985, 41/3 (639-643)

Vitamin K deficiency results in the appearance of abnormal prothrombin, deficient in gamma-carboxyglutamic acid, in the blood. The presence of abnormal prothrombin can be eliminated or lowered by the administration of vitamin K. Since the abnormal prothrombin antigen assay is approximately 1000-fold more sensitive than the prothrombin time for the diagnosis of vitamin K deficiency, this assay was used to evaluate patients with intestinal abnormalities. Vitamin K deficiency was found in 18 of 58 patients (31%) with chronic gastrointestinal disease and/or resection. All patients with vitamin K deficiency had either Crohn's disease involving the ileum or ulcerative colitis treated with sulfasalazine or antibiotics. Abnormal prothrombin levels returned toward normal in patients treated with vitamin K but not in patients who were not treated with vitamin K. The mean plasma vitamin E level in patients with vitamin K deficiency was significantly lower than in vitamin-K sufficient patients (p<0.01). We conclude that certain chronic forms of gastrointestinal disorders are associated with vitamin K deficiency.

Galvez J.; Cruz T.; Crespo E.; Ocete M.A.; Lorente M.D.; Sanchez de Medina E.; Zarzuelo A.
J. Galvez, Department of Pharmacology, School of Pharmacy, University of Granada, Poligono de Cartuja s/n, E-18071, Granada Spain
Planta Medica (Germany), 1997, 63/5 (409-414)

The effect of the flavonoid rutoside on acetic acidinduced rat colitis was studied. Rats were pretreated orally with different doses of the flavonoid (10, 25, and 100 mg/kg) 48, 24, and 1 hour prior to colitis induction and examined for colonic damage 24 hours later. Colonic inflammation was characterized by gross and microscopical injury, bowel wall thickening, abolition of fluid absorption, glutathione depletion, enhanced leukotriene B4 synthesis, and increased levels of myeloperoxidase and alkaline phosphatase activities. Rutoside treatment (25 and 100 mg/kg) reduced histologic injury and prevented the increase in alkaline phosphatase activity, but it had no effect on myeloperoxidase levels or leukotriene B4 synthesis. In addition, glutathione depletion was effectively counteracted at the dose of 25 mg/kg, whereas fluid absorption was achieved at the highest dose assayed. It is concluded that rutoside has an acute antiinflammatory activity in this model which may be related to a putative direct protective effect on intestinal cells, mainly enterocytes, in which the antioxidative properties of the flavonoid may play a role.

De Medina F.S.; Galvez L.-H.; Romero J.A.; Zarzuelo A.
F.S. De Medina, Department of Pharmacology, School of Pharmacy, University of Granada, 18071 Granada Spain
Journal of Pharmacology and Experimental Therapeutics (USA), 1996, 278/2 (771-779)

Quercitrin was tested for acute and chronic anti-inflammatory activity in trinitrobenzenesulfonic acid-induced rat colitis. The inflammatory status was evaluated by myeloperoxidase, alkaline phosphatase and total glutathione levels, leukotriene B4 synthesis, in vivo colonic fluid absorption, macroscopical damage and occurrence of diarrhea and adhesions. Treatment with 1 or 5 mg/kg of quercitrin by the oral route reduced myeloperoxidase and alkaline phosphatase levels, preserved normal fluid absorption, counteracted glutathione depletion and ameliorated colonic damage at 2 days. Increasing or lowering the dose of the flavonoid resulted in marked loss of effect. The acute anti-inflammatory effect of quercitrin is unrelated to impairment of neutrophil function or lipoxygenase inhibition, and it may be caused by mucosal protection or enhancement of mucosal repair secondary to increased defense against oxidative insult and/or preservation of normal colonic absorptive function. When tested in chronic colitis (2 and 4 weeks), quercitrin treatment (1 or 5 mg/kg . day) decreased colonic damage score and the incidence of diarrhea, and normalized the colonic fluid transport. All other parameters were unaffected. The chronic effect of the flavonoid is apparently related to its action on colonic absorption, although it can be partly secondary to its acute beneficial effect.

Bokkenheuser V.
Department of Pathology, St. Luke's-Roosevelt Hospital Center, 1111 Amsterdam Avenue, New York, NY 10025 USA
Clin. Infect. Dis. (USA), 1993, 16/Suppl. 4 (S427-S434)

Anaerobic bacteria include the most pathogenic of microorganisms. Their primary function, however, is hardly to cause illness. They rarely are involved in epidemics or in clinically significant infections. Some organisms, e.g. lactobacilli, control the normal vaginal ecosystem, and the intestinal anaerobes probably are instrumental in restraining the growth of Clostridium difficile in human carriers. The main role of anaerobes appears to be the provision of catabolic enzymes for organic compounds that cannot be digested by enzymes of eukaryotic origin. They are needed for the catabolism of cholesterol, bile acids, and steroid hormones; they hydrolyze a number of flavonoid glycosides to anticarcinogens; and they detoxify certain carcinogens. Anaerobic enzymes are used industrially in the production of cheese; the conversion of starch to sweeteners; and the transformation of sawdust, wood chips, and waste paper to fuel. Indeed, the anaerobes may well be the gene bank on which future generations of eukaryotic organisms will rely to adapt successfully to an ever-changing world.

Fernandez-Banares F.; Mingorance M.D.; Esteve M.; Cabre E.; Lachica M.; Abad-Lacruz A.; Gil A.; Humbert P.; Boix J.; Gassull M.A.
Department of Gastroenterology, Hospital Universitari 'Germans Trias I Pujol', Carretera del Canyet 2/n, 08916 Badalona Spain
Am. J. Gastroenterol. (USA), 1990, 85/12 (1584-1589)

Serum levels of zinc, copper, and selenium, and alkaline phosphatase activity were prospectively studied in 29 patients with inflammatory bowel disease. Fifteen patients had extensive active colitis (active colitis group). Seven patients had active, and seven cases inactive small bowel or ileocecal Crohn's disease (small bowel disease group). Ninety-three healthy subjects acted as controls. Serum trace element levels were considered in relation to vitamin A and E levels, nutritional parameters, the activity of the disease, and the recent intake of steroids. The effect of total enteral nutrition on serum trace elements was studied in seven cases. Serum zinc levels were lower and serum copper levels higher in the active colitis group than in controls (p = 0.0007, and p = 0.02, respectively). More than 50% of patients with active colonic or small bowel disease showed zinc levels below the 15th percentile of the control group. Serum zinc levels correlated with plasma vitamin A in acute colitis (r = 0.67; p = 0.006), and with both serum albumin concentration (r = 0.76; p = 0.002) and disease activity score (r = -0.67, p = 0.009) in patients with small bowel disease. The copper:zinc ratio was higher in the active colitis group than in controls (p = 0.002). In spite of the increase in serum albumin levels and the decrease in disease activity, serum zinc levels remained low after total enteral nutrition. The implications of the abnormal trace element status in patients with inflammatory bowel disease are discussed.

Gee M.I.; Grace M.G.A.; Wensel R.H.; et al.
Department of Food and Nutrition, Faculty of Home Economics, University of Alberta, Edmonton, Alta. Canada
J. Am. Diet. Assoc. (USA), 1985, 85/12 (1591-1599)

Dietary intakes of two groups of gastrointestinal patients, one group with inflammatory bowel disese (IBD) - Crohn's disease or chronic ulcerative colitis - and the other with functional disorders (FD) - irritable bowel syndrome, nonulcer dyspepsia or gastroesophageal reflux disease, were assessed by means of 48-hour recalls. The relationships between dietary intake and anthropometric and biochemical measurements were examined. The IBD group had lower mean serum albumin and hemoglobin levels (p < .05); however, FD patients had less adequate diets. The mean energy intake of women with FD was significantly lower than that of women with IBD (p < .05) and was associated with inadequate or marginal intakes of many nutrients. Comparison of nutrient intakes between the IBD and FD groups revealed a significantly lower mean intake of folate, ascorbic acid, and vitamin A for women with FD than for women with IBD (p < .05). In general, women had poorer diets and a higher prevalence of abnormal biochemical parameters than men. One notable feature of the dietary pattern of the women was that they consumed less meat than the general population consumed. Increasing meat consumption would improve the intake of many nutrients, including protein and iron. The results of this study suggest that more attention should be given to the adequacy of dietary intakes of gastrointestinal patients in general and of women in particular.

Pirzer U, Schonhaar A, Fleischer B, Hermann E, Meyer zum Buschenfelde KH
First Department of Medicine, University of Mainz, Germany.
Lancet 1991 Nov 16;338(8777):1238-9

Intestinal T lymphocytes are normally unresponsive to microbial and recall antigens in vitro, whereas the same antigens induce strong immune responses in peripheral-blood-derived T cells. We obtained T lymphocytes from peripheral blood and from the non-inflamed and inflamed intestinal mucosa of 6 patients (3 male, 3 female; mean age 33 years) with Crohn's disease. The T cells were stimulated in vitro with a range of microbial antigens. Whereas T cells from normal mucosa were unresponsive, those from inflamed mucosa had a proliferative response comparable to that of the peripheral-blood-derived T cells. These findings suggest that physiologic unresponsiveness to luminal antigens is abrogated in the inflammatory lesions of Crohn's disease patients. Infiltrating T lymphocytes may therefore mediate chronic inflammation on encountering the many antigens present in the intestine.

Straub RH, Vogl D, Gross V, Lang B, Scholmerich J, Andus T
Department of Internal Medicine I, University Medical Center, Regensburg, Germany.
Am J Gastroenterol 1998 Nov;93(11):2197-202

OBJECTIVES: Dehydroepiandrosterone sulfate (DHEAS) and cortisol are multifunctional adrenal hormones with immunomodulating properties. DHEAS levels were found to be very low in chronic inflammatory diseases. This study aimed to shed more light on the interrelation between DHEAS and cortisol (and humoral markers of inflammation) in chronic inflammatory bowel disease.

METHODS: DHEAS and cortisol serum levels were measured by ELISA in the serum of 66 normal subjects, 115 patients with Crohn's disease (CD) and 64 patients with ulcerative colitis (UC). Humoral markers of inflammation and disease activity scores were assessed by standard techniques.

RESULTS: DHEAS was lower in patients with CD (p < 0.005) and UC (p < 0.005) than in controls, which was, in part, dependent on previous corticosteroid treatment (p < 0.01). In CD patients, z-normalized DHEAS was inversely correlated with blood sedimentation rate (p = 0.017). Z-normalized DHEAS was negatively correlated with interleukin-6 (IL-6) in the form of a trend (p = 0.068), and z-normalized DHEAS was significantly positively correlated with hemoglobin (p = 0.001) but not with the Crohn's disease activity index. Cortisol, however, was positively correlated with blood sedimentation rate (p = 0.034) and C-reactive protein (p = 0.006). In contrast, in UC patients no such correlation of z-normalized DHEAS or cortisol and parameters of humoral inflammatory activity or Rachmilewitz index exist.

CONCLUSIONS: DHEAS as a marker of inflammation was low in CD and UC. In CD patients, low DHEAS and high cortisol serum levels were associated with higher humoral inflammatory activity. With respect to humoral inflammatory activity in CD patients, DHEAS and cortisol seem to be inversely regulated, which may have an impact on several immune functions, such as IL-6 secretion.

Christl SU Eisner HD Dusel G Kasper H Scheppach W.
Dig Dis Sci (1996 Dec) 41(12):2477-81I

It has been shown that feces of patients with ulcerative colitis uniformly contain sulfate reducing bacteria. Sulfide produced by these bacteria interferes with butyrate-dependent energy metabolism of cultured colonocytes and may be involved in the pathogenesis of ulcerative colitis. Mucosal biopsies from the sigmoid rectum of 10 patients (no cancer, polyps, inflammatory bowel disease) were incubated with either NaCl, sodium hydrogen sulfide (1 mmol/L), a combination of both sodium hydrogen sulfide and butyrate (10 mmol/L), or butyrate. Mucosal proliferation was assessed by bromodeoxyuridine labeling of cells in S-phase. Compared to NaCl, sulfide increased the labeling of the entire crypt significantly, by 19% (p < 0.05). This effect was due to an expansion of the proliferative zone to the upper crypt (compartments 3-5), where the increase in proliferation was 54%. Sulfide-induced hyperproliferation was reversed when samples were coincubated with sulfide and butyrate. The study shows that sodium hydrogen sulfide induces mucosal hyperproliferation. Our data support a possible role of sulfide in the pathogenesis of UC and confirm the role of butyrate in the regulation of colonic proliferation and in the treatment of UC.

Motley RJ Crawley EO Evans C Rhodes J Compston JE.
Gut (1988 Oct) 29 (10):1332-6

The rate of spinal trabecular bone loss during one year was measured in 54 patients with inflammatory bowel disease. The mean change in spinal bone mineral content was -5.1 mg/ml K2HPO4, representing 3% of the initial bone mineral content. The rate of bone loss showed a significant negative correlation with body mass index (r = -0.276, p less than 0.05) but no other significant correlations were found with other clinical or biochemical indices, including the total amount of prednisolone taken during the course of the study. Eleven patients had bone loss greater than 15 mg/ml/year; these included four non steroid-treated patients, two of whom had disease confined to the large bowel. The results indicate rapid rates of bone loss in some patients with inflammatory bowel disease over the course of one year. Although steroid therapy and malnutrition are likely to be contributory factors in some patients, other as yet unidentified risk factors also operate. The rapid bone loss observed in some patients emphasises the need for effective prophylactic regimes.

Marcus R Butterfield G Holloway L Gilliland L Baylink DJ Hintz RL Sherman BM.
J Clin Endocrinol Metab (1990 Feb) 70(2):519-27

We evaluated the effects of recombinant human GH (rhGH) in 16 men and women more than 60 yr of age. After 10 days of dietary equilibration and control collections, subjects were randomly assigned to receive 0.03, 0.06, or 0.12 mg/kg rhGH by daily injection for 7 days. A brisk rise in circulating somatomedin-C (insulin-like growth factor-I) occurred in all subjects, and this rise was dose dependent. RhGH produced striking changes in nitrogen retention, sodium excretion, and the parathyroid-vitamin D axis. Twenty-four-hour urinary nitrogen excretion decreased from 8.00 +/- 0.33 to 5.01 +/- 0.33 g (P less than 0.001), and sodium excretion decreased from 45.9 +/- 2.96 to 21.2 +/- 3.48 mmol/day (P less than 0.001). Serum calcium concentrations did not change, but serum inorganic phosphorus levels of 1.08 +/- 0.04 mmol/L at baseline increased significantly after rhGH treatment to 1.33 +/- 0.04 mmol/L (P less than 0.001). Increases were also observed in circulating PTH (53.2 +/- 6 vs. 39.5 +/- 4.2 ng/L; P less than 0.01) and calcitriol (82.8 vs. 65.8 pmol/L; P less than 0.05). A rise in serum osteocalcin (10.3 +/- .86 vs. 8.0 +/- 0.5 micrograms/L; P less than 0.05) was accompanied by increased urinary excretion of hydroxyproline (628 +/- 63 vs. 406 +/- 44 mumol/day; P less than 0.01). Despite the reduction in sodium excretion, marked increases were observed in urinary calcium (6.04 +/- 0.97 vs. 3.27 +/- 0.40 mmol/day; P less than 0.01). rhGH significantly impaired oral glucose tolerance and reduced insulin sensitivity, but was otherwise well tolerated and produced no systematic changes in weight or blood pressure. The results of this study indicate that RhGH requires further study as a potential agent for attenuating or reversing the loss of muscle and bone in elderly people.

Almallah YZ, Richardson S, O'Hanrahan T, Mowat NA, Brunt PW, Sinclair TS, Ewen S, Heys SD, Eremin O
Department of Surgery, University of Aberdeen, United Kingdom.
Am J Gastroenterol 1998 May;93(5):804-9

OBJECTIVES: Recently, it has been postulated that patients with ulcerative colitis have altered natural cytotoxicity, in particular natural killer (NK) and lymphokine-activated killer (LAK) cell activities. These cellular mechanisms have been postulated to play an etiological role in the pathogenesis of the disease process. We have shown previously that the essential fatty acids (EFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) specifically inhibit natural cytotoxicity. Our aim was to evaluate the role of omega-3 EFA in the modulation of natural cytotoxicity and disease activity in patients with distal procto-colitis.

METHODS: In this pilot study patients were randomized into two groups. Each patient received either fish oil extract (EPA, 3.2 g, and DHA, 2.4 g) (n = 9) or sunflower oil (placebo) (n = 9) daily in a double-blind manner for 6 months. Monthly assessments of disease activity (clinical and sigmoidoscopic scores) and histological evaluation of mucosal biopsies were carried out. Also, the circulating levels and activities of NK and LAK cells, using flow cytometric analysis (CD16+ CD56+) and in vitro 51 chromium release assays (K562), respectively, were monitored.

RESULTS: After 6 months' supplementation with EFA, there was improvement in the clinical activity compared with pretreatment evaluation. There was significant reduction in the sigmoidoscopic and histological scores in the EFA group compared with the placebo group. Essential fatty acid supplementation for 6 months also induced significant reduction in the circulating numbers of CD16+ and CD56+ cells and the cytotoxic activity of NK cells, compared with the placebo group.

CONCLUSIONS: This pilot study has demonstrated that omega-3 fatty acids can suppress natural cytotoxicity and reduce disease activity in patients with distal procto-colitis. These findings suggest a therapeutic strategy for managing patients with inflammatory bowel disease.

Mascolo N, Izzo AA, Autore G, Maiello FM, Di Carlo G, Capasso F
Department of Experimental Pharmacology, University of Naples, Federico II, Naples, Italy.
J Pharmacol Exp Ther 1995 Jan;272(1):469-75

Eicosanoids and platelet-activating factor (PAF) production increases in experimental colitis. Both eicosanoids and PAF seem to arise from similar membrane phospholipids. To support both these suggestions we have investigated whether a fat-free diet, which should alter production of eicosanoids and PAF, affects experimental colitis. Essential fatty acid deficient (EFAD) rats were obtained by putting 4-week-old animals on a fat-free diet for 3 months. Experimental colitis was induced by a single intracolonic administration of 2 ml of 4% acetic acid. One to seven days later the animals were sacrificed and the colon removed to assess macroscopically and histologically intestinal damage. Eicosanoids and PAF levels were also measured in the mucosa scrapings by specific radioimmunoassay. The injury to the colon was more evident in control rats compared with EFAD rats. Besides colonic tissue of control rats showed a highly significant increase of PGE2, LTB4 and PAF, compared with levels in EFAD rats. Our results indicate that fat-free diet reduces tissue damage, and at the same time PGE2, LTB4 and PAF colonic content.

Simopoulos AP
Center for Genetics, Nutrition and Health, Washington, DC.
Am J Clin Nutr 1999 Sep;70(3 Suppl):560S-9S

Human beings evolved consuming a diet that contained about equal amounts of n-3 and n-6 essential fatty acids. Over the past 100-150 y there has been an enormous increase in the consumption of n-6 fatty acids due to the increased intake of vegetable oils from corn, sunflower seeds, safflower seeds, cottonseed, and soybeans. Today, in Western diets, the ratio of n-6 to n-3 fatty acids ranges from approximately 20-30:1 instead of the traditional range of 1-2:1. Studies indicate that a high intake of n-6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggregatory, characterized by increases in blood viscosity, vasospasm, and vasoconstriction and decreases in bleeding time. n-3 Fatty acids, however, have antiinflammatory, antithrombotic, antiarrhythmic, hypolipidemic, and vasodilatory properties. These beneficial effects of n-3 fatty acids have been shown in the secondary prevention of coronary heart disease, hypertension, type 2 diabetes, and, in some patients with renal disease, rheumatoid arthritis, ulcerative colitis, Crohn disease, and chronic obstructive pulmonary disease. Most of the studies were carried out with fish oils [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. However, alpha-linolenic acid, found in green leafy vegetables, flaxseed, rapeseed, and walnuts, desaturates and elongates in the human body to EPA and DHA and by itself may have beneficial effects in health and in the control of chronic diseases.

Han PD, Burke A, Baldassano RN, Rombeau JL, Lichtenstein GR
University of Pennsylvania School of Medicine, Philadelphia, USA.
Gastroenterol Clin North Am 1999 Jun;28(2):423-43, ix

This article reviews the nutritional aspects of inflammatory bowel disease (IBD) including the mechanisms and manifestations of malnutrition and the efficacy of nutritional therapies. Nutrient deficiencies in patients with IBD occur via several mechanisms and may complicate the course of the disease. Nutritional status is assessed by clinical examination and the use of nutritional indices such as the Subjective Global Assessment of nutritional status. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need parenteral nutrition.

Nieto N, Fernandez MI, Torres MI, Rios A, Suarez MD, Gil A
Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Granada, Spain.
Dig Dis Sci 1998 Dec;43(12):2676-87

The intrarectal administration of trinitrobenzene sulfonic acid in rats induces ulcerative colitis, which results in histological alterations of colonic mucosa, severe modification of the cellular antioxidant defense system, and enhanced production of inflammatory eicosanoids. This study evaluated the influence of different dietary fatty acids, i.e., monounsaturated, n-3, and n-3 + n-6 polyunsaturated fatty acids, on the recovery of the colonic mucosa histological pattern, the cellular antioxidant defense system of colon, and PGE2 and LTB4 colonic mucosa contents in a model of ulcerative colitis induced by intrarectal administration of trinitrobenzene sulfonic acid. Administration of dietary n-3 polyunsaturated fatty acids led to a minimum stenosis score, a higher histological recovery, lower colon alkaline phosphatase and gamma-glutamyltranspeptidase activities, and lower mucosal levels of PGE2 and LTB4 compared with the other two experimental groups. However, glutathione transferase, glutathione reductase, glutathione peroxidase, and catalase activities were lower in the group treated with n-3 polyunsaturated fatty acids than in the groups fed with either the monounsaturated or the n-6 + n-3 polyunsaturated enriched diet. We conclude that n-3 polyunsaturated fatty acids can be administered to prevent inflammation in ulcerative colitis, but they cause a decrease in the colonic antioxidant defense system, promoting oxidative injury at the site of inflammation.

Akisu M, Baka M, Coker I, Kultursay N, Huseyinov A
Department of Pediatrics, Ege University Medical School, Izmir, Turkey
makisu@hotmail.com
Biol Neonate 1998;74(1):31-8

Necrotizing entercolitis (NEC) is an important neonatal disease with a high mortality rate. Inflammatory mediators, such as mainly platelet-activating factor (PAF), leukotrienes (LT) and tumor necrosis factor play an important role in the genesis of NEC. Diets in omega-3 (n-3) fatty acids appear to have an antiinflammatory effect, which is thought to be due to decreased active prostaglandins and leukotrienes production after incorporation of these fatty acids into cell membrane phospholipids. We investigated the protective effect of fish oil (source of n-3 fatty acids) on hypoxia-induced model of NEC. Young mice were divided into three groups; group 1 mice were fed standard chow (n-3 fatty acids-free), group 2 was fed a chow supplemented by 10% fish oil for 4 weeks. Group 3 mice served as control. We examined the intestinal lesions by light microscopy and measured intestinal tissue PAF and LB4 levels in hypoxia-induced model of NEC. Significantly increased intestinal PAF and LTB4 levels were found in group 1 mice when compared to group 2 and group 3 mice. The histopathology of the intestinal lesions in group 1 animals was characteristic of ischemic injury. In the n-3 fatty acids-supplemented animals these lesions were milder. The present study shows that endogenously released PAF and LTB4 play an important role in mediating hypoxia-induced intestinal necrosis. The present study also suggests that dietary supplementation with n-3 fatty acids suppress intestinal PAF and LTB4 generation in hypoxia-induced bowel necrosis. The intestinal protective effect of n-3 fatty acids in an experimental model of NEC may open new insight into the treatment and prevention of NEC in neonates.

Hunter JO
Addenbrooke's Hospital, Gastroenterology Research Unit, Cambridge, UK.
Eur J Gastroenterol Hepatol 1998 Mar;10(3):235-7

During the past 20 years there has been growing interest in the importance of nutritional factors in the pathogenesis of inflammatory bowel disease. There are so far no definite links between ulcerative colitis and diet, but links with Crohn's disease have been studied by both epidemiologists and clinicians. Epidemiological studies, although retrospective, have suggested that patients with Crohn's disease eat more sugar and sweets that control individuals; however, when dietary sugar is restricted, there is little clinical benefit. The clinical approach to nutrition in Crohn's disease has been by the use of elemental diets, which will produce symptomatic and objective remission in up to 90% of compliant patients. Those who return to normal eating soon relapse but, in some studies, have enjoyed prolonged remission on exclusion diets. The foods excluded have been not sugar, but predominantly cereals, dairy products and yeast. Attention has now switched to the possible harmful role of fat in Crohn's disease. The efficacy of elemental feeds appears to depend not on the presentation of nitrogen but on the amount of long chain triglyceride present. Increases in recent years in the frequency of Crohn's disease in Japan have been correlated with increased dietary fat intake, and a recent study suggested that W-3 fatty acids, which are metabolized by immunomodulatory leukotrienes and prostaglandins, may have a beneficial role to play. The links between nutrition and Crohn's disease have now become strong and the role of fat may be the most exciting of all.

[Article in Spanish]
Jorquera Plaza F, Espinel Diez J, Olcoz Goni JL
Seccion de Digestivo, Hospital de Leon, Espana.
Nutr Hosp 1997 Nov-Dec;12(6):289-98

Malnutrition is a very common situation in patients inflammatory with intestinal disease (IID), which can be caused by a multitude of factors. It has been shown that nutritional support not only improves the nutritional condition of the patients, but in Crohn's disease it also has an effect on the activity of the disease, although this effect is smaller than that of steroids. Elemental diets are no more efficient than polymeric diets except under very special circumstances, but they are more expensive and patients tolerate them worse. A digestive pause is not recommended unless there is an absolute contraindication for the use of the digestive tract. Therefore, parenteral nutrition, which is more expensive and can cause serious complications, will be reserved for very specific indications. The use of fish oil supplements, either because it competes with arachidonic acid and prevents the initiation of the inflammatory cascade, or because it decreases the production of cytokines, has shown to be potentially useful in inflammatory intestinal disease, and this must be confirmed by further studies. Short chain fatty acids enemas have shown promising results in distal ulcerative colitis but the lack of homogeneity in the studies makes it necessary for these results to be consolidated in new studies. Nutritional support is especially interesting in children with inflammatory intestinal disease given that the growth retardation which is often seen in severe cases, can be controlled by adequate enteral or parenteral diets.