Acute-phase protein response to infection in severe malnutrition

It is not known whether malnourished infant can mount a comprehensive acute-phase protein (APP) response and, if so, whether this is achieved by increasing APP synthesis rates. To address these issues, we measured 1) the plasma concentrations of five APPs (C-reactive protein, O1-acid glycoprotein, O1-antitrypsin, haptoglobin, and fibrinogen) and 2) the synthesis rates of three APPs (O1-antitrypsin, haptoglobin, and fibrinogen) using a constant intragastric infusion of [2H3] leucine in nine infected marasmic children at 2 days postadmission (study 1), 9 days postadmission when infections had cleared (study 2), and 59 days postadmission at recovery (study 3). Except for fibrinogen, the plasma concentrations of all APPs were higher in study 1 than in studies 2 and 3. Although the rate of synthesis of haptoglobin was significantly greater in study 1 than in study 2, the rates of fibrinogen and O1-antitrypsin synthesis were similar in all three studies. These results show that 1) severely malnourished children can mount an APP response to infection which does not include fibrinogen and 2) the APP response is accomplished through different mechanisms. (AU)

Protein-losing enteropathy and trichuriasis - abstract

The phenomenon of protein-losing enteropathy (PLE) is defined as the abnormal loss of serum proteins into the gastrointestinal tract resulting from a variety of gastrointestinal abnormalities. Infestation of the large bowel and terminal ileum by adult Trichuris trichiura results in inflammatory reactions surrounding the sites of attachment. This study establishes Trichuris dysentery syndrome as one of the clinical disorders characterized by PLE. The clearance by the gut alpha-1-antitrypsin (OAT), a serum protein that resists proteolysis by digestive enzymes, was assessed in (i) subjects infected by the parasitic nematode and presenting with the Trichuris dysentery syndrome, and (ii) subjects manifesting no gastrointestinal diseases nor having conditions or receiving drugs likely to cause PLE. All subjects were within the age range 3 through 11 years, inclusive. A linear regression analysis showed a significant correlation between clearance of O AT and adult worm count (r = 0.4, p<0.05). The daily loss of this amount of serum protein is likely to be a considerable part of the cost to the host of this chronic parasitic infection (AU)

Plasma protein response in children with trichuris dysentry syndrome - abstract

In Trichuris Dysentry Syndrome (TDS), we have elsewhere shown an IgE-mediated mucosal mast cell inflammatory response and infiltration of the colonic lamina propria by macrophages with evidence of the cellular production to TNF O. There is an increased concentration of this cytokine in the systemic circulation: both this and the correlation of finger-clubbing with worm load are evidence of an inflammatory response which is systemic as well as local to the intestine. We therefore assayed the plasmas of 53 TDS children, 16 "disease control" (DC) and 20 "normal control" (NC) children for plasma protein changes. DC children were Trichuris negative patients who had clinical indications for colonoscopy, mainly chronic diarrhoea; NC were trichuris-negative asymptomatic children of similar background to the TDS patients who were subjected to venepuncture and non-invasive tests of intestinal permeability and intestinal protein clearance (normal). There was a significant increase (p<0.05) in the means of C-Reactive protein (CRP) and antitrypsin in the TDS compared with the NC group. The mean increase in the DC group was significantly differernt from the NC. The reduction in the mean albumin concentration in TDS compared with NC children was not quite significant (p=0.05). Caeruloplasmin showed a significant difference only between the DC and NC children (p < 0.05). The other plasma proteins assayed, transferrin and fibrinogen, showed no significant difference in their means among the three groups. These changes in plasma protein concentrations are indicative of a generalized sytemic response to Trichuris trichuria and correspond to a continuous, mile "acute phase response" to this chronic infection (AU)

Familial pulmonary emphysema - abstract

Two brothers, aged 39 years and 37 years, of African origin, attending the University Hospital of the West Indies, have been shown to have familial pulmonary emphysema with a severe depletion in serum alpha - 1 antitrypsin levels, the main proteinase inhibitors in human serum. Previous reports of this disorder have come from the United States of America and Europe. This is the first report from the Caribbean, and the second of its occurrence in subjects of African descent. The elder brother, who is the worse affected, noted breathlessness from 27 years of age, and is now totally disabled. The younger brother, became dyspnoeic at 32 years and now has to stop for breath after walking 100 yard, Both have a chronic cough with intermittent sputum production. Initially they were heavy smokers, but dyspnoea has forced the younger brother to reduce his consumption, and the elder brother to give up the habit. Chest radiographs and , in the younger brother lung volume and pulmonary gas transfer studies confirm emphysema. The elder brother is too ill to have lung function tests. The disease is inherited as a Mendelian recessive disorder. Serum alpha - 1 antitrypsin levels of both brothers are less than 25 mg per cent indicative of the homozygous state. The mother, one brother, and all three of the patients' children are heterozygotes for the gene with levels between 25 mg and 150 mg per cent. One brother and two sisters, and all their children have normal levels in excess of 150 mg per cent. The father died some years ago, but had no history of lung disease. The nature of the association between pulmonary emphysema and low levels of serum alpha - 1 antitrypsin remains uncertain (AU)