Decreased sensitivity of artesunate and chloroquine of Plasmodium falciparum infecting hemoglobin H and/or hemoglobin constant spring erythrocytes.

Plasmodium falciparum infecting hemoglobin (Hb) H and/or Hb Constant Spring erythrocytes in vitro was relatively more resistant than that infecting normal erythrocytes to artesunate and chloroquine, while the sensitivity to pyrimethamine was unchanged. The 50% inhibitory concentrations (IC50) for artesunate in HbH (alpha-thal 1/alpha-thal 2), HbH (alpha-thal 1/Hb Constant Spring), and homozygous Hb Constant Spring erythrocytes were 4.5 +/- 2.8, 8.5 +/- 3.2, and 2.6 +/- 1.6 nM compared with 0.82 +/- 0.35 nM in normal erythrocytes (P less than 0.002 for all three cases). The IC50 for chloroquine were 97 +/- 46, 162 +/- 67, and 93 +/- 36 nM, respectively, in the variant erythrocytes, compared with 48 +/- 13 nM in normal erythrocytes (P less than 0.002, 0.002, and 0.02, respectively). The differences in sensitivity to artesunate and chloroquine of the parasite infecting HbH erythrocytes are probably related to their oxidative mode of action and relatively high amounts of antioxidant enzymes in the host erythrocytes. This novel example of dependence on the host of the malarial parasite drug sensitivity may have implications for chemotherapy of malaria in patients with genetically variant erythrocytes.     

Different patterns of intraerythrocytic inclusion body distribution in the two types of haemoglobin H disease. An ultrastructural study

Electron microscopic examination of intraerythrocytic inclusion bodies induced by methylene blue was carried out in 7 non-splenectomized patients with haemoglobin (Hb) H disease. In classical Hb H disease with the genotype of alpha-thalassaemia 1/alpha-thalassaemia 2 the inclusion bodies were mostly membrane-associated. In contrast, in Hb H disease of alpha-thalassaemia 1/Hb Constant Spring genotype the majority of inclusion bodies were in a floating stage. Possible mechanisms for the unexpected difference are discussed.     

Increased phagocytosis of Plasmodium falciparum-infected erythrocytes with haemoglobin E by peripheral blood monocytes

Erythrocytes from subjects with homozygous and heterozygous haemoglobin E (HbE) infected with Plasmodium falciparum in vitro were phagocytosed to a greater extent by normal human monocytes than infected erythrocytes from normal subjects. Susceptibility to phagocytosis was maximal when the parasites developed to trophozoite and schizont stages in both normal and patients' erythrocytes. The increased susceptibility of P. falciparum-infected HbE erythrocytes to phagocytosis by monocytes may play a role in protection against malaria.     

Automated cytochemistry in non-Hodgkin's lymphoma: a new method for determination of cells from lymph node biopsy

Cell suspension prepared from the lymph node biopsy of patients with non-Hodgkin's lymphoma (NHL), metastatic carcinoma (MC) and non-neoplastic lymphadenopathies (NL) were analyzed by the Hemalog D, automated differential counter. The preparation of lymph node cells is described first in this study. The results show that the percentage of large cells (diameter greater than 13.5 micron) stained negatively with peroxidase (LUC, large unstained cells) was remarkably increased in patients with NHL (mean +/- SEM = 18.6 +/- 3.1%) and was particularly increased in the subgroup, diffuse histiocytic type (31.1 +/- 5.3%). Patients with MC had a raised percentage of nonspecific esterase-positive cells (9.2 +/- 1.4%) compared to patients in the NHL and NL groups. Patients in the NL group had low percentages of both LUC (5.3 +/- 0.7%) and nonspecific esterase-positive cells (1.8 +/- 0.2%). Quantitation of cells in the lymph node by using the Hemalog D may assist in the diagnosis of lymph node diseases.     

Serum vitamin A and E in pregnant women with hemoglobinopathies.

OBJECTIVE: To evaluate the relationship between the status of serum vitamin A, E and hemoglobinopathies among Thai pregnant women. METHODS: This was a cross-sectional study in which serum vitamin A and E were assessed in 323 pregnant women with normal hemoglobin and 73 with hemoglobinopathies (47 with hemoglobin E and 26 with thalassemia) during the first trimester. RESULTS: There were no significant differences in the mean serum vitamin A, E concentrations and vitamin E/cholesterol ratio between pregnant women with normal hemoglobin and hemoglobinopathies, while confounding variables that might affect serum vitamin levels i.e. maternal age, gravida, BMI, gestational age, hematocrit, hemoglobin, mean corpuscular hemoglobin concentration and blood group were not different. CONCLUSION: The results of this study suggest that antenatal care in terms of micronutrients-vitamin A, E in Thai pregnant women with hemoglobinopathies should not be different from normal pregnant women.     

Hepatic Megalocytosis in Chronic Lasiocarpine Poisoning: Some Functional Studies

In an attempt to understand the nature of cytoplasmic and nuclear enlargement of liver cells designated as megalocytosis that results from chronic poisoning by lasiocarpine, a pyrrolizidine alkaloid, certain functional aspects of these cells were investigated together with the study of their morphology. The RNA polymerase activity of the megalocyte nuclei was essentially comparable to the activity observed in normal liver cells. Further, the inducibility of tryptophan pyrrolase activity by hydrocortisone, in the livers of rats treated chronically with lasiocarpine is an indication that translational mechanisms are intact. However, the increased uptake of 3H-thymidine by megalocytes, in the absence of observable mitotic activity, suggests that these cells are in the process of hypertrophy. It is concluded that the megalocytes are functionally normal cells, except that they are in the process of cellular hypertrophy and are incapable of division due to potent antimitotic action of the pyrrolizidine alkaloids.     

Erythrocyte volume and haemoglobin concentration in haemoglobin H disease: discrimination between the two genotypes.

Erythrocyte volume and haemoglobin concentration in individual red cells from 62 patients with Hb H disease: 37 with H genotype (alpha-thalassaemia 1/alpha-thalassaemia 2) and 25 H/CS genotype (alpha-thalassaemia 1/Hb Constant Spring) were measured using the H*1 haematology analyser. All 25 cases with H/CS genotype, the more severe genotype, had microcytes (red cells with a volume smaller than 60 fl) less than 35% and hypochromic red cells (red cells with haemoglobin concentration less than 28 g/dl) more than 35%. A discriminant function, the ratio between the percentage of hypochromic red cells and the percentage of microcytes (Hypo/Micro), was proposed. Most of the H/CS patients (76%) had Hypo/Micro greater than 2.5 whereas those of H patients (82%) were below 2.5. Red cell volume histograms were also characteristically different between the two genotypes: the H/CS had a peak between 60 and 90 fl while the H genotype showed a peak at or very close to 60 fl, indicating a greater degree of microcytosis. Increased hypochromia with a slight decrease in cell size of H/CS red cells suggests that the poor degree of haemoglobinization has no linkage or very little role in disturbing the synthesis of membrane proteins and their assembly to the plasma membrane.