Kupffer cell function during the erythocytic stage of malaria.

BACKGROUND AND AIM: Previous studies using isolated perfused rat liver in vivo have suggested that during the erythrocytic phase of malaria infection, overall phagocytosis by Kupffer cells is enhanced. The aim of the present study was to further investigate the individual phagocytic capacity and prostaglandin E(2) (PGE(2)) secretion of isolated Kupffer cells in vitro, and the immunohistochemical characteristics of Kupffer cells in vivo. METHODS: Malaria was induced in male Sprague-Dawley rats (n = 12) by inoculation with parasitized red cells containing Plasmodium berghei. Kupffer cells were isolated by centrifugal elutriation. RESULTS: A significantly increased yield of Kupffer cells was obtained from malaria-infected livers compared to controls (36.7 +/- 4.5 vs 11.8 +/- 1.1 x10(6) cells, P < 0.0001, n = 12). There was an increased internalization by phagocytosis of [(3)H]-BSA latex microspheres after 60 min in malaria-infected Kupffer cells compared to controls (65.05 +/- 1.5 vs 48.6 +/- 0.7, P < 0.001, n = 12). PGE(2) secretion into the cell culture medium was significantly suppressed in malaria-infected Kupffer cells compared to controls (1167 +/- 88 vs 4537 +/- 383 pg per 10(6) cells, P < 0.001, n = 5). Staining of ED1, ED2 and PCNA was greater in malaria-infected livers compared to control. CONCLUSION: The results indicate that the number of Kupffer cells is significantly increased and their phagocytic activity on a cell-by-cell basis is enhanced during the erythrocytic stage of malaria.

Hepatic Kupffer cell phagocytotic function in rats with erythrocytic-stage malaria.

BACKGROUND: In the erythrocytic phase of malaria, Kupffer cells show marked hypertrophy and hyperplasia and are filled with malarial pigment. However, phagocytic function in this state has not been well characterized. The aim of the present study was to use mouse Plasmodium berghei to infect rats with malaria and study the phagocytic function and morphology of Kupffer cells. METHODS: We used a recirculating isolated perfused rat liver (IPRL) to quantitate Kupffer cell phagocytic clearance of radiolabeled albumin-latex over 120 min in high parasitemia (53 +/- 6%; n = 7) and low parasitemia (approximately 1%; n = 4) malaria-infected rats and littermate controls (n = 7 and n = 4, respectively). In a further group of high-parasitemic rats, perfusion was ceased after 7 min and liver radioactivity also measured. Electron microscopy was performed after perfusions. RESULTS: In high-parasitemia malaria rats, clearance of radiolabeled latex from IPRL perfusate over 120 min was significantly (P < 0.01) faster than in controls, with a lower area under the curve (0.19 +/- 0.02 vs 0.43 +/- 0.07 /mL per min, respectively) and shorter half-life (t1/2k; 2.4 +/- 0.6 vs 10.0 +/- 2.3 min, respectively). Low-parasitemia rats were identical to controls. After 7 min perfusion in high-parasitemic rats (n = 4), total radioactivity in liver homogenates was higher than in controls (n = 4; 33.1 +/- 6.2 vs 18.4 +/- 1.9% of injected radiolabel; P < 0.05). Electron microscopy showed latex in Kupffer cells, more abundantly seen in high-parasitemic animals. CONCLUSIONS: Total Kupffer cell phagocytic activity of the liver is markedly increased in rats with a high parasitemic load of malarial P. berghei infection. This is presumed to reflect an upregulation of scavenger activity phagocytosing erythrocytes and their breakdown products.

Randomized comparison of nasojejunal and nasogastric feeding in critically ill patients.

OBJECTIVE: Critically ill patients often develop large gastric residual volumes during nasogastric feeding as a result of poor gastroduodenal motility. Nasojejunal feeding may decrease the severity of this complication. The aim of this study was to determine whether nasojejunal feeding improved tolerance of enteral nutrition by reducing gastric residual volumes. DESIGN: Randomized, prospective, clinical study. SETTING: Intensive care unit of a university-affiliated hospital. PATIENTS: Seventy-three intensive care unit patients expected to require nutritional support for at least 3 days. INTERVENTIONS: Patients were randomized to receive enteral nutrition via a nasojejunal tube (placed endoscopically) (34 patients) or a nasogastric tube (39 patients). A strict protocol was followed, which included regular gastric residual volume measurement (in both groups), the use of predetermined criteria for intolerance, and an attempt at nasojejunal feeding for those nasogastrically fed patients who were intolerant of enteral nutrition. MEASUREMENTS AND MAIN RESULTS: Endoscopic placement of nasojejunal tubes was successful in 98% with no complications of insertion. Patients fed via a nasojejunal tube had 1) a reduced total gastric residual volume in both the first 24 (197 vs. 491 mL, p = .02) and 48 hrs (517 vs. 975 mL, p = .02); 2) a reduced incidence of a single gastric residual volume >150 mL (32% vs. 74%, p = .001); and 3) a trend toward a reduced incidence of intolerance of enteral nutrition (13% vs. 31%, p = .09). Only 13% of those nasogastrically fed patients who were initially intolerant of enteral nutrition remained intolerant once fed via a nasojejunal tube, and only 1.4% of all patients met criteria for commencement of parenteral nutrition. CONCLUSIONS: Enteral nutrition delivered via a nasojejunal tube is associated with a significant reduction in gastric residual volume, a strong trend toward improved tolerance of enteral nutrition, and an extremely low requirement for parenteral nutrition.