Serum Ornithine Carbamoyl Transferase as a Surrogate Marker in Malaria

Ornithine carbamoyl transferase (OCT) activity and other liver function tests were studied in a total of 50 patients of clinical malaria and 15 controls. They were grouped as group I (positive for malarial parasite on peripheral blood smear, n=18), group II (negative for malarial parasite on peripheral blood smear (PBS) but responded to antimalarials, n=17) and group III (peripheral blood smear negative and did not respond to antimalarial therapy, n=15). The mean OCT levels were significantly raised in group I (6.79 ± 1.84 IU/L, p value = 0.006) and group II (5.0 ± 1.15 IU/L, p value = 0.014) as compared to controls (2.5 ± 1.13 IU/L) and returned to normal after treatment In contrast, group III had normal levels except in a case of kala azar and septicemia where OCT levels were high and increased further on treatment. Taking PBS positivity as a gold standard of diagnostic criteria, OCT had a sensitivity of 83% and specificity of 86% with a high positive predictive value of 88% as compared to ALT which had a lower sensitivity of 55% and specificity of 80%. The clinical response rate in PBS negative cases of fever having high OCT level was 83% as compared to 35% in cases with normal OCT level, making OCT a good surrogate marker of malaria. OCT levels could also be of prognostic significance as 2 cases of cerebral malaria had high OCT levels of 11.1 UAL and 10.7 IU/L, respectively.Key Words: Malaria, Ornithine carbamoyl transferase     

Birth of Healthy Children After Preimplantation Diagnosis of Thalassemias

Background: Preimplantation genetic diagnosis (PGD) allows couples at risk of having children with thalassemia to ensure the healthy outcome of their pregnancy. Methods: Seventeen PGD clinical cycles were initiated for Cypriot couples at risk of having children with different thalassemia mutations, including IVS1-110, IVSI-6, and IVSII-745. Unaffected embryos for transfer were selected by testing oocytes, using first and second polar body (PB) removal and nested polymerase chain reaction analysis followed by restriction digestion. Results: Unaffected embryos were selected in 16 of 17 PGD cycles. Of 166 oocytes studied from these cycles, 110 were analyzed by sequential analysis of both the first and the second PB, resulting in preselection and transfer of 45 unaffected embryos. This resulted in seven pregnancies and in the birth of five healthy thalassemia-free children. The embryos predicted to have inherited the affected allele were not transferred. Analysis of these embryos confirmed the PB diagnosis. Conclusions: Sequential first and second PB testing of oocytes is reliable for PGD of thalassemia and is a feasible alternative to prenatal diagnosis in high-risk populations.     

The effect of compounds with antioxidant properties on thrombocyte functional activity

The effect of antioxidant compounds ionol and mexidol and the new phenol derivative N9-imidazo-(1,2 alpha)-benzymidazol (PY-185) on the functional activity of blood platelets was studied. All the compounds under study effectively inhibited blood platelet aggregation both in vitro and in administration into rats, a result of which the blood thrombogenic potential reduced.     

Spectrin-alpha I/61: a new structural variant of alpha-spectrin in a double-heterozygous form of hereditary pyropoikilocytosis

Recent biochemical studies have led to the identification of abnormal spectrins in the erythrocytes of patients with hereditary pyropoikilocytosis (HPP) and hereditary elliptocytosis (HE). In this report we describe the biochemical characterization of the erythrocytes from a proband with severe HPP who is doubly heterozygous for two mutant spectrins (Sp): Sp alpha I/74 and a new, previously undetected, mutant of alpha-spectrin designated Sp alpha I/61. The proband's erythrocytes are unstable when exposed to 45 degrees C, and her membrane skeletons exhibit instability to shear stress. The content of spectrin in the proband's erythrocyte membranes is decreased to 75% of control values. The amount of spectrin dimers in crude 4 degrees C spectrin extracts is increased (58%) as compared with control values (6% +/- 4%). Limited tryptic digestion reveals a marked decrease in the normal 80,000-dalton alpha I domain, an increase in the 74,000-dalton fragment that is characteristic of Sp alpha I/74, and an increase in a series of new fragments of 61,000, 55,000, 21,000, and 16,000 daltons. Both parents are asymptomatic, but they have increased amounts of spectrin dimers (17% to 25%). Limited tryptic digestion of the father's spectrin demonstrates the presence of a previously identified abnormal spectrin (Sp alpha I/74) that is characterized by a decrease in content of the 80,000-dalton peptide and an increase in concentration of the 74,000-dalton peptide. The mother's spectrin digests show a decrease in the amount of 80,000-dalton peptide and the formation of new peptides of 61,000, 55,000, 21,000, and 16,000 daltons. The data indicate that this severe form of HPP is due to the inheritance of two distinct abnormal spectrins, Sp alpha I/74 and a new spectrin mutant, Sp alpha I/61.     

Diagnosing and preventing inherited disease: Pregnancies following pre-conception diagnosis of common aneuploidies by fluorescent in-situ hybridization

Chromosomal aneuploidies contribute considerably to the lowpregnancy rate in in-vitro fertilization (IVF). The objectiveof this experimental work was to explore the possibility ofdetecting common aneuploidies in oocytes by polar body sampling.The study included 45 infertile patients of advanced maternalage participating in an IVF programme. The first polar bodywas removed prior to fertilization or both the first and secondpolar bodies were removed after fertilization and studied byfluorescent in-situ hybridization (FISH) using chromosome-specificprobes for chromosomes X, 18 and/or 13/21. Of 155 oocytes withFISH results, 36 demonstrated chromosomal abnormalities. Of119 oocytes predicted to be free from aneuploidy of chromosomesX, 18 and/or 13/21, 72 were normally fertilized, cleaved andtransferred in 23 treatment cycles, which resulted in two healthydeliveries and three ongoing pregnancies confirmed to be unaffectedby chorionic villous sampling. The method may appear usefulfor the detection of oocytes with common chromosomal aneuploidiesin IVF patients of advanced maternal age.