Cause Of Malabsorption Research Articles

Celiac disease and skin: Psoriasis association

TO THE EDITOR We read with great interest the recent review by Rodrigo on the celiac disease (CD). The author analyzed all aspects of CD. Contrary to common belief, this disorder is a systemic disease, rather than a pure digestive alteration. In fact, CD is associated with several diseases: skin manifestations, endocrine disorders, iron-deficiency anemia, osteoporosis, hypertransaminasemia, neurologic disorders and cancer. In the description of skin manifestations, the author reported the association between CD and dermatitis herpetiformis (DH). This condition affects about 15%-25% of patients with CD. Antibodies for CD have been detected in patients with DH. As CD and DH may be vastly different, they both share a unique intestinal sensitivity to gluten. The rash of DH is thought to be an external marker of the underlying intestinal sensitivity that is likely to be the result of molecular mimicry between the auto-antigen tissue transglutaminase resident in the gut and the skin derived epidermal transglutaminase. However, our study group has reported all CD-associated skin manifestations described in the literature, and in particular psoriasis. Psoriasis is a chronic, relapsing dermatosis characterised by scaling, erythema, and less commonly pustulation. It has been demonstrated that psoriasis is an immunological disease with hyperproliferation of T-cell mediated keratocytes. Immune mechanisms play an important role in the pathogenesis of this disease. In particular, an overexpression of T helper cell type 1 (Th1) cytokines and a relative under-expression of Th2 cytokines have been shown in psoriatic patients. Recent studies showed an association between CD and psoriasis and an improvement of skin lesions after 3-6 mo of gluten free diet (GFD), without other pharmacological approaches. The authors evaluated the effect of GFD in 33 antigliadin antibody (AGA) positive patients and six AGA negative patients with psoriasis in an open study. Of the 33 AGA-positive patients, two had IgA anti-endomysial antibodies (EMA), and at the duodenal biopsy 15 showed an increased number of lymphocytes in the epithelium, but in some patients, this increase was only slight. GFD was started for 3 months. Thirty of 33 patients strictly complied with GFD, have showed a significant decrease of psoriatic lesions. This included a significant decrease in the 16 AGA positive patients with normal histology in duodenal biopsy. The AGA negative patients did not improve. There was also a significant decrease in serum of eosinophil cation protein in patients with elevated AGA. In conclusion, the positive effects of GFD were observed not only in patients with an increased number of lymphocytes in the duodenal epithelium, but also in patients with normal epithelium. We reported severe psoriasis in a CD patient, not responding to specific therapies for psoriasis and in whom the regression of skin lesions after GFD was very rapid. The association between psoriasis and CD was subsequently confirmed by Ojetti et al. The authors evaluated the prevalence of CD in patients affected by psoriasis, and found a high frequency of CD (4.34%) in psoriatic patients. At present, the mechanisms implicated in this association, and the effect of GFD on psoriatic skin lesions are not known. There are some hypotheses: (1) Abnormal small intestinal permeability could be a triggering factor between CD and psoriasis; (2) T cells play an important role in the pathogenesis of both psoriasis and CD. In CD patients, gliadin induces a sensitisation of T cells and this may play a role in the pathogenesis of psoriatic skin lesions; (3) Psoriatic lesions in CD patients could be related to vitamin D deficiency, which is present in both CD and psoriasis. In a recent study, the prevalence of malabsorption in 55 psoriatic patients was evaluated. The authors found that malabsorption was more prevalent among psoriatic patients than among controls and suppose that celiac disease and other diseases associated with psoriasis, such as bacterial overgrowth, parasitic infestations and eosinophilic gastroenteritis, could be the causes of malabsorption in these patients. In conclusion, CD is an enteropathy associated with various extra-intestinal manifestations, including several skin diseases. DH represents the cutaneous manifestation of celiac disease. However, other skin manifestations of CD have been reported in literature, particularly the psoriasis. At present, the data are not homogeneous and

The pathology of malabsorption: current concepts

Intestinal malabsorption results from a wide variety of causes, which can most easily be organized into three groups. Maldigestion arises from problems with mixing or with digestive mediators, and includes post-gastrectomy patients and those with deficiencies of pancreatic or intestinal enzymes, or of bile salts. Mucosal and mural causes of malabsorption are abundant, and include gluten-sensitive enteropathy, tropical sprue, autoimmune enteropathy, and HIV/AIDS-related enteropathy, as well as mural conditions such as systemic sclerosis. Finally, microbial causes of malabsorption include bacterial overgrowth, Whipple's disease, and numerous infections or infestations that are most frequently seen in immunocompromised patients. An overview of the most common and interesting entities in each of these categories follows, along with a discussion of current concepts. Mucosal conditions and microbial causes of malabsorption are given special attention.

Coeliac disease: relationship to endocrine autoimmunity

Coeliac disease is a common cause of malabsorption. It is associated with a genetic predisposition but environmental influences are important. A number of disorders are associated with coeliac disease including type 1 diabetes and Addison’s disease. A small bowel biopsy is required to make the diagnosis and treatment consists of a gluten-free diet. This short report describes a male with Addisons who went on to develop type 1 diabetes and coeliac disease. The discussion reviews coeliac disease and its associations. Case history

Celiac Sprue Associated Membranoproliferative Glomerulonephritis

A 50 year old hispanic male with hypertension, urticaria pigmentosa, vitamin B 12 deficiency and anemia was evaluated for chronic diarrhea and was diagnosed to have celiac sprue with positive antigliadin antibodies. He also complained of having a foamy urine but did not undergo formal evaluation of kidney function initially.He was started on a gluten free diet with resolution of diarrheal symptoms but kept having proteinuria and soon developed swelling of both his lower extremities. Subsequent evaluation revealed the presence of nephrotic syndrome with a 24 hour urine protein of 4.7 gms. He had a serum creatinine of 1.2mg/dl, Hemoglobin of 10.5 g/dl, low C3 and normal C4 levels. A kidney biopsy performed diagnosed him to have membranoproliferative glomerulonephritis(MPGN). He was started on PO steroids (without any cytotoxic agents) which he received for 6 months. He responded to treatment after six months of therapy and has stayed in disease remission. Celiac sprue is a common cause of malabsorption in Caucasians, and the etiology of the disease is suspected to involve environmental, immunologic and genetic factors. The immunologic components suspected are the IgA antibodies (IgA antigliadin, IgA antiendomysial and IgA anti-tissue transglutaminase). Circulating immune complexes have been noted to be deposited in the kidney and are occasionally implicated in causing IgA nephropathy. But the occurence of MPGN in the setting of Celiac disease is more infrequent. We report this rare occurence of MPGN in a patient with celiac disease. The potential significance of identifying patients with celiac disease to have MPGN may have important implications to understanding the etiology of these diseases. This case suggests that the possible source of antigen in celiac disease with MPGN may be of a dietary origin which required treatment with steroids to maintain remission of disease.

Digestive functions

Most foods cannot be absorbed in the form in which they are present but require digestion into smaller compounds that can be more easily absorbed. The basic process of digestion for the three major foods (carbohydrates, proteins, fats) is hydrolysis. Most absorption takes place in the small intestine. The processes of digesting carbohydrates, proteins and fats are described in detail. The absorption of ions and water is also discussed. The causes of malabsorption are identified.

Malabsorption in psoriatic patients: Cause or consequence?

Objective. The aetiopathogenesis of psoriasis is still unclear. Associations between gut and skin diseases are well known, since psoriatic patients show a high prevalence of coeliac disease. Small-bowel abnormalities can cause clinical or, more frequently, laboratory alterations that give rise to malabsorption. The aim of the study was to evaluate the prevalence of malabsorption in psoriatic patients. Material and methods. Fifty-five (29 M, 26 F, mean age 51±8 years) psoriatic patients in the Dermatology Centre of our hospital and 65 healthy controls (36 M, 29 F, mean age 47±9 years) were screened for malabsorption using a D-xylose test. Psoriatic subjects who resulted positive were further investigated in order to reach a better characterization of the malabsorption using serum antigliadin, antiendomysium and anti-transglutaminase antibodies, H2 lactulose breath test, the parasitological faecal test and colonoscopy with retrograde ileoscopy. Results. Altered D-xylose absorption was found in 60% (33/55) of psoriatic patients and in 3% (2/65) of controls. Of the former, 6% had coeliac disease, 21% had bacterial overgrowth, 3% had parasitic infections and 1 patient presented eosinophilic gastroenteritis. Conclusions. Malabsorption was more prevalent among psoriatic patients than among controls. Coeliac disease, bacterial overgrowth, parasitic infestations and eosinophilic gastroenteritis could be possible causes of malabsorption in these patients. Further studies are needed to clarify the pathogenesis and possible causative associations between gut and skin diseases.

Limitations of faecal elastase-1 and chymotrypsin as tests of exocrine pancreatic disease in adults

The faecal enzymes elastase and chymotrypsin are a relatively inexpensive non-invasive means of investigating causes of malabsorption. However, such tests may be affected by enzyme degradation or faecal dilution. Faecal elastase-1 and chymotrypsin were measured in 225 patients in whom pancreatic disease was suspected, and the association between faecal free water and pH with these faecal enzymes was examined in subjects with normal pancreatic function. The sensitivity of faecal elastase-1 and chymotrypsin for identifying exocrine pancreatic disease was 75% and 60%, respectively. Corresponding specificities for excluding disease were 95% and 97%. The positive predictive value for faecal elastase-1 increased from 58% to 92% when watery diarrhoea was excluded. Faecal elastase-1 (inversely) and chymotrypsin (directly) were significantly associated with percentage faecal free water content in subjects without pancreatic disease. Faecal elastase-1 was not related to faecal pH, whereas chymotrypsin was inversely related to pH. Faecal elastase-1 is a more sensitive test for exocrine pancreatic disease in adults but is affected by dilution in patients with watery diarrhoea. The value of faecal chymotrypsin is limited by intestinal degradation.

Treatment Options for Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases that affect 0.5 to 40 per 100,000 and 1 to 6 per 100,000 Americans, respectively. Prompt recognition and management of the clinical manifestations of these diseases is essential for the patients' well-being and ultimate outcome. Ursodeoxycholic acid (UDCA), 13 to 15 mg/kg per day, is the standard therapy for PBC and should be offered to every patient. It has been shown to slow progression of the disease and prevent the need for liver transplantation, which is the last recourse for patients with end-stage disease. However, there is no effective therapy for PSC yet. Patients are managed symptomatically, with surgical or endoscopic interventions as needed in cases of significant biliary obstruction. Complications of chronic cholestasis are seen in both PBC and PSC, with pruritus and fatigue being the most common complaints. The first choice for the treatment of pruritus is still cholestyramine, starting at 4 g/d. The pathogenesis of fatigue is poorly understood in this population; unrecognized hypothyroidism should be excluded. The use of antidepressants is currently under evaluation, but there is no specific therapy for fatigue as of yet. For prevention of severe osteoporosis, we recommend supplementation with 800 IU vitamin D and 1500 mg calcium/d. In patients with PBC and established osteoporosis, the use of alendronate and vitamin K appears to cause an increase in bone mineral density. Further studies are necessary before either of these drugs is routinely recommended. Finally, fat-soluble vitamin deficiencies are noted with more advanced disease. We recommend that serum levels be checked in high-risk patients, and that vitamins are replaced as appropriate with water-soluble supplements. However, other causes of malabsorption must be ruled out, including pancreatic insufficiency and celiac sprue.

Bone mineral density and importance of a gluten-free diet in patients with celiac disease in childhood.

Celiac disease (CD), a common cause of malabsorption, is known to be associated with disorders of the skeleton, but there are conflicting data about the effect of diet on bone metabolism. The aims of this study were to investigate the prevalence of osteopenia; to identify the relationship between bone mineral density (BMD), serum calcium, and parathyroid hormone levels; and to determine the effect of gluten-free diet on BMD in children with celiac disease. The study included 32 patients with CD (group 1) and 82 healthy controls (group 2). The patients with CD were evaluated under 2 subgroups, ie, 16 patients with recent diagnosis (group 1a) and 16 patients who follow their diet strictly (group 1b). BMD values and concentrations of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were determined on entry to the study and at 12 months in celiac patients. These values were compared with those of healthy control participants. BMD and bone mineral content values in patients with recent diagnosis were found to be significantly lower than the control group. The BMD values in patients with recent diagnosis were significantly increased after a gluten-free diet for 1 year. Osteopenia was found more commonly in patients with recent diagnosis than patients in whom a gluten-free diet had been instituted. At 1-year follow-up, osteopenia was not resolved with the gluten-free diet, and this was especially true in patients without gastrointestinal manifestation. In patients with recent diagnosis (group 1a), the mean calcium level was found to be lower than the patients who follow their diet strictly (group 1b). There was a positive correlation between calcium level and BMD and bone mineral content. BMD is almost invariably low in newly diagnosed celiac patients in childhood. We therefore recommend that BMD should be evaluated in patients with CD. Strict gluten avoidance promoted a significant increase in BMD. However, values still remained markedly low after 1 year of follow-up in some patients. These patients should be followed for longer periods of time with yearly BMD evaluation, as 1 year of diet therapy was found to be insufficient for osteopenia to be resolved.

DIARRHEA AND MALABSORPTION IN THE ELDERLY

Physicians who care for elderly patients should be alert to the possible presence of diarrhea and malabsorption. Older patients may not admit to having chronic diarrhea, particularly if they also are incontinent. If diarrhea is of short duration, an infectious cause is at least as common as in the young. Institutionalized elderly are particularly prone to gastrointestinal infections, but the manifestations may not be overt. When an intestinal infection and potential medication-induced gastrointestinal disturbances have been excluded, the differential diagnosis of diarrhea in the elderly is the same as in the young. Causes include intestinal malabsorption, even though diarrhea is a less common manifestation of malabsorption in the old than in younger patients. In the elderly, micronutrient deficiency is a common presenting clinical picture; because the symptoms of malabsorption are covert, the diagnosis often is delayed, and nutritional deficiencies are more common and more severe than in the young. Because the elderly have less nutritional reserve than the young, these deficiencies are clinically much more devastating in the elderly. Although the causes of malabsorption, as a whole, are similar in older and younger patients, chronic pancreatic insufficiency of unknown cause and intestinal bacterial overgrowth without an anatomic abnormality of the small intestine are syndromes that are specific to the elderly and must be considered in any older patient with unexplained weight loss or failure to thrive. Often, therapeutic trials are necessary to establish a potential diagnosis.

Celiac disease: the past, the present, the future.

* Abbreviations: CD = : celiac disease • HLA = : human leukocyte antigen • EmA = : antiendomysium antibodies • TJ = : tight junction • TTG = : tissue transglutaminase Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten-containing grains (ie, wheat, barley, and rye) in susceptible individuals. Both in vivo challenges and in vitro immunologic studies support the possibility that oat (once considered toxic for CD patients) can be safely ingested.1 However, because of uncontrolled harvesting and milling procedures, a cross-contamination of oat with gluten is a concern. It is the gliadin fraction of wheat gluten, and similar alcohol-soluble proteins in other grains, that are the environmental factors responsible for the development of the intestinal damage. The disease is associated with human leukocyte antigen (HLA) alleles DQA1\*0501/DQB1\*0201, and in the continued presence of gluten the disease is self-perpetuating.2 The typical intestinal damage characterized by loss of absorptive villi and hyperplasia of the crypts completely resolves on elimination of gluten-containing grains from the patients' diet. CD represents a common cause of malabsorption in western countries with apparent geographic variation in incidence. In the second century AD, Aretaeus from Cappadocia described what is believed to be the first report of a gastrointestinal condition resembling CD.3 Approximately 1700 years later, the connection between the ingestion of certain cereals and the onset of gastrointestinal symptoms typical of CD was established.4For the past 18 centuries, CD has been perceived as a disease whose clinical presentation was quite uniform. The case identification was entirely based on the search for symptoms such as chronic diarrhea, abdominal distension, and weight loss (or poor weight gain) occurring in young children a few weeks/months after the introduction of solid food to their diet. Therefore, early epidemiologic studies targeted the pediatric population experiencing this typical clinical presentation of the disease. In the past 5 decades, a substantial number of epidemiologic studies have been conducted in Europe to establish the frequency of …

Detection of impaired intestinal absorption of long-chain fatty acids: validation studies of a novel test in a rat model of fat malabsorption

Classic fat balance studies detect fat malabsorption but do not discriminate between the potential causes of malabsorption, such as impaired intestinal lipolysis or reduced uptake of fatty acids. We aimed to validate a novel test for the specific, sensitive detection of impaired intestinal uptake of long-chain unesterified fatty acids in an appropriate rat model of fat malabsorption. The absorption and appearance in plasma of [(13)C]palmitic acid were determined in control rats and in rats with fat malabsorption due either to chronic bile deficiency (permanent bile diversion) or to oral administration of the lipase inhibitor orlistat (200 mg/kg diet). [(13)C]Palmitic acid results were compared with the percentage absorption of ingested dietary fat determined by fat balance. Between 1 and 6 h after intraduodenal administration, plasma [(13)C]palmitate concentrations in control rats were 4-10-fold higher than in bile-deficient rats (P < 0.05) but were not significantly different between orlistat-supplemented rats and their controls. In control and bile-deficient rats, plasma [(13)C]palmitate concentrations allowed complete discrimination between normal (>92%) and reduced (<92%) fat absorption, whereas the percentage absorption of [(13)C]palmitate over 48 h appeared to be highly correlated with the percentage absorption of ingested dietary fat (r = 0.89, P < 0.001). The [(13)C]palmitic acid absorption test detects impaired intestinal absorption of long-chain fatty acids selectively and sensitively in a rat model of fat malabsorption due to bile deficiency. Our data strongly support the use of the [(13)C]palmitic acid absorption test for the diagnosis of clinical fat malabsorption syndromes.

Postgastrectomy pancreatic malabsorption

More patients are surviving surgery for gastric carcinoma than ever before. The possible causes of malabsorption following total gastrectomy are multifactorial, and pancreatic insufficiency has been proposed as one mechanism. Other contributing factors include loss of gastric reservoir, rapid small bowel transit, small bowel bacterial overgrowth and the type of operation performed. Although pancreatic exocrine insufficiency has been demonstrated after gastrectomy, the key question remains whether pancreatic enzyme supplements offer any substantial clinical benefit to the patient. The evidence to date does not support the routine use of pancreatic enzyme supplementation after gastrectomy.

Vitamin K deficiency embryopathy: A phenocopy of the warfarin embryopathy due to a disorder of embryonic vitamin K metabolism

Three unrelated infants presented with radiographic punctate calcifications, nasal hypoplasia, and abnormalities of the spine. Additional anomalies included cupped ears in 2 patients and one each with Dandy-Walker malformation with hydrocephaly, congenital cataracts, and peripheral pulmonary artery stenosis. The mothers of these 3 patients had chronic conditions associated with intestinal malabsorption requiring total parenteral nutrition for varying periods of time. The underlying causes of malabsorption were celiac disease, short bowel syndrome secondary to surgical resection, and jejuno-ileal bypass, respectively. Bleeding diathesis occurred in one mother requiring vitamin K supplementation during the second and third trimesters of pregnancy. We speculate that the chondrodysplasia punctata and other abnormalities in these children were caused by an acquired maternal vitamin K deficiency manifested during early pregnancy. However, the involvement of other vitamin deficiencies cannot be excluded. Thus, vitamin K deficiency of the embryo secondary to maternal malabsorption appears to be a third vitamin K-related mechanism leading to chondrodysplasia punctata in addition to warfarin embryopathy and epoxide reductase deficiency (pseudo-warfarin embryopathy). Am. J. Med. Genet. 72:129–134, 1997. © 1997 Wiley-Liss, Inc.

Vitamin K deficiency embryopathy: A phenocopy of the warfarin embryopathy due to a disorder of embryonic vitamin K metabolism

Three unrelated infants presented with radiographic punctate calcifications, nasal hypoplasia, and abnormalities of the spine. Additional anomalies included cupped ears in 2 patients and one each with Dandy-Walker malformation with hydrocephaly, congenital cataracts, and peripheral pulmonary artery stenosis. The mothers of these 3 patients had chronic conditions associated with intestinal malabsorption requiring total parenteral nutrition for varying periods of time. The underlying causes of malabsorption were celiac disease, short bowel syndrome secondary to surgical resection, and jejuno-ileal bypass, respectively. Bleeding diathesis occurred in one mother requiring vitamin K supplementation during the second and third trimesters of pregnancy. We speculate that the chondrodysplasia punctata and other abnormalities in these children were caused by an acquired maternal vitamin K deficiency manifested during early pregnancy. However, the involvement of other vitamin deficiencies cannot be excluded. Thus, vitamin K deficiency of the embryo secondary to maternal malabsorption appears to be a third vitamin K-related mechanism leading to chondrodysplasia punctata in addition to warfarin embryopathy and epoxide reductase deficiency (pseudo-warfarin embryopathy).

A Standardized Diet for Performing Fecal Fat Excretion Studies

Quantitative fecal fat excretion analysis is a test that is frequently used in the evaluation of diarrhea and malabsorption. Unfortunately, the dietary fat intake during the testing period influences the outcome. The clinical usefulness of the test can thereby be affected. We propose the use of a standardized diet for timed analysis of fecal fat excretion. We also provide 2 sample menus that can be used for this purpose. Quantitative analysis of fecal fat excretion has become an invaluable tool in the evaluation of diarrhea. The protocol described by Van de Kamer et al¹in 1949 is still used today, with only minor modifications. The test is clinically useful in determining the cause of diarrhea. Other investigators have suggested that the degree of steatorrhea is helpful in distinguishing pancreatic insufficiency from other causes of malabsorption,^2,3The dilemma concerning the determination of fecal fat excretion during a timed interval

Where have all the American celiacs gone?

Celiac disease is a common cause of malabsorption in western countries, with significant geographic variation in incidence. Recent epidemiological studies using serology tests, however, suggest that the disease is more common than previously realized and homogeneously distributed in Europe. These studies have also demonstrated that the clinical presentation of the disease may greatly vary even between neighboring countries. Celiac disease remains a rare diagnosis in the United States. Whether the disease is underdiagnosed or is truly rare remains to be established. We have conducted preliminary studies, both on pediatric patients and adult blood donors, that seem to suggest that the prevalence of positive screening tests for celiac disease in the USA is equivalent to that reported in similar screening studies conducted in Europe. These data also suggest that the dimensions of the American celiac disease iceberg seem to be similar to those of the European one. The visible tip of the American iceberg, however, appears to be much smaller, since most of it still remains submerged. The reasons for these divergences remain unknown and may only be partially related to the limited attention to the disease by the American scientific community. Large, multicenter serological screening studies are needed to define the true prevalence of celiac disease in the United States.

Screening for coeliac disease as a possible maternal risk factor for neural tube defect

Coeliac disease is an important cause of malabsorption, particularly of folic acid, in adults. We investigated the possibility that it might be a maternal risk factor for neural tube defect (NTD)-associated pregnancy by screening affected mothers using serum endomysial antibody (EmA) which has high sensitivity and specificity for coeliac disease. One (1.6%) of 60 patients was EmA positive and had a diagnosis of coeliac disease confirmed by the finding of villous atrophy on jejunal biopsy. In conclusion, the majority of NTD-associated pregnancies are not associated with maternal coeliac disease and our study is additional evidence that abnormalities of folic acid metabolism rather than absorption are the most important risk factors for NTD. Further studies are needed to determine whether the coeliac disease prevalence among women with NTD-affected pregnancy is higher than that of the general population.

Lipid deposition in intestine as a possible cause of malabsorption of nutrients in zinc-deficient common carp (Cyprinus carpio).

An experiment was performed to examine the interaction between Zn deficiency and lipid intake in carp. The carp were given a high-lipid diet that was either Zn-deficient (ZD) or Zn-supplemented (ZS), or were pair-fed (PF) the ZS diet to the intake of the ZD group. After 8 weeks the carp were killed and measurements were made of intestinal glucose uptake, levels of DNA, RNA and triacylglycerol, and alkaline phosphatase (EC 3.1.3.1) activity in liver and intestine samples. A further group of similar carp were given the same diets but at week 8 were transferred to low-lipid diets, with the exception of half the ZD group. After a further 8 weeks of treatment, carps were killed for biochemical studies. Intestinal [14C]glucose uptake, levels of DNA, RNA and alkaline phosphatase activity in intestine and liver were significantly (P < 0.05) lower in the high-lipid ZD group than in the high-lipid ZS and PF diet groups. The triacylglycerol concentration in the intestine was higher in the high-lipid ZD group than in the other two groups. When the carp were given the corresponding low-lipid diets, the variables measured in intestine and liver of the ZD group were close to those of the other groups. The results of this study demonstrate that lipid, when present in excess in the diet, accumulates in the intestine under Zn-deficient conditions and may reduce the absorption of glucose in carp. The reduced RNA and DNA levels and alkaline phosphatase activity in liver and intestine of ZD fish compared with those of ZS fish given high-lipid diets is proposed to be due to the malabsorption of nutrients linked with lipid deposition in the intestine, rather than their dependence on the level of Zn in the diet.

Development of malabsorption and nutritional complications in simian immunodeficiency virus-infected rhesus macaques

To assess the development and cause of malabsorption in rhesus macaques following experimental simian immunodeficiency virus (SIV) infection and to evaluate its impact on nutritional status. Clinical malabsorption tests and serial jejunal aspirates and biopsies were obtained from nine SIV-infected and three uninfected animals prior to infection and at 1, 2, 4, 8, 12, 24, 40 and 52 weeks postinoculation. Malabsorption was measured by sucrose breath hydrogen (H2) analysis and blood assay of D-xylose. Digestive enzyme activity was determined in jejunal mucosal homogenates. Bacterial and protozoal flora were determined in jejunal aspirates. Nutritional assessment was evaluated using specific blood micronutrient values. Cellular targets of SIV in the jejunum were determined by combined in situ hybridization and immunohistochemistry. Eight out of nine SIV-infected monkeys, including asymptomatic animals, exhibited malabsorption by either increased breath H2 and/or decreased blood D-xylose. All animals that died of AIDS had diarrhea, D-xylose malabsorption and decreased sucrase activity. Significant changes in nutritional status were associated with malabsorption. Bacterial overgrowth was not considered to be a cause of malabsorption. Histopathological biopsy findings included dilated villus lacteals, excessive cellular debris, lymphoplasmocytic infiltrates and cytoplasmic vacuoles in crypt epithelial cells. SIV-infected T cells and macrophages were detected as early as 1 week postinoculation. SIV-associated malabsorption can occur prior to clinical complications of disease. Severe intestinal complications are associated with malabsorption and malnutrition in the terminal stages of AIDS. The high proportion of macaques experiencing malabsorption without detectable pathogens, suggests an enteropathogenic role for SIV.