|
Sulfapyride and sulfones decrease
glycosaminoglycans viscosity in dermatitis herpetiformis,
ulcerative colitis, and pyoderma gangrenosum
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.
The glycosaminoglycans of the human colon in
inflammatory and neoplastic conditions
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.
Inflammatory bowel disease: Another possible facet
of the allergic diathesis
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.'
The effect of proctocolectomy on serum antibody
levels against cow's milk proteins in patients with chronic
ulcerative colitis, with special reference to liver
changes
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.
Isotypic analysis of antibody response to a food
antigen in inflammatorybowel disease
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.
The biological activity of bovine cartilage
preparations
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.
HLA-B27 related arthritis and bowel inflammation.
Part 1. Sulfasalazine (salazopyrin) in HLA-B27 related
reactive arthritis
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.
HLA-B27 related arthritis and bowel inflammation.
Part 2. Ileocolonoscopy and bowel histology in patients with
HLA-B27 related arthritis
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.
Circulating antioxidants in ulcerative colitis and
their relationship to disease severity and activity
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.
Nutritional assessment and disease activity for
patients with inflammatory bowel 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.
The role of antioxidant agents on experimental
ulcerative colitis
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.
Does vitamin E supplementation modulate in vivo
arachidonate metabolism in human inflammation?
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.
The prevalence of vitamin K deficiency in chronic
gastrointestinal disorders
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.
Rutoside as mucosal protective in acetic
acid-induced rat colitis
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.
Effect of Quercitrin on acute and chronic
experimental colitis in the rat
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.
The friendly anaerobes
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.
Serum zinc, copper, and selenium levels in
inflammatory bowel disease: Effect of total enteral nutrition
on trace element status
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.
Nutritional status of gastroenterology outpatients:
Comparison of inflammatory bowel disease with functional
disorders
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.
Reactivity of infiltrating T lymphocytes with
microbial antigens in Crohn's disease.
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.
Association of humoral markers of inflammation and
dehydroepiandrosterone sulfate or cortisol serum levels in
patients with chronic inflammatory bowel disease.
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.
Antagonistic effects of sulfide and butyrate on
proliferation of colonic mucosa: a potential role for these
agents in the pathogenesis of ulcerative colitis.
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.
Increased rate of spinal trabecular bone loss in
patients with inflammatory bowel disease.
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.
Effects of short term administration of recombinant
human growth hormone to elderly people.
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.
Distal procto-colitis, natural cytotoxicity, and
essential fatty acids.
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.
Acetic acid-induced colitis in normal and essential
fatty acid deficient rats.
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.
Essential fatty acids in health and chronic
disease.
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.
Nutrition and inflammatory bowel disease.
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.
Dietary monounsaturated n-3 and n-6 long-chain
polyunsaturated fatty acids affect cellular antioxidant
defense system in rats with experimental ulcerative colitis
induced by trinitrobenzene sulfonic acid.
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.
Effect of dietary n-3 fatty acids on
hypoxia-induced necrotizing enterocolitis in young mice. n-3
fatty acids alter platelet-activating factor and leukotriene
B4 production in the intestine.
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.
Nutritional factors in inflammatory bowel
disease.
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.
[Inflammatory bowel disease: importance of
nutrition today].
[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.
|