In erythroid cells, more than 90% of transferrin-derived iron enters mitochondria where ferrochelatase inserts Fe into protoporphyrin IX. However, the path of iron from endosomes to mitochondrial ferrochelatase remains elusive. The prevailing opinion is that, after its export from endosomes, the redox-active metal spreads into the cytosol and mysteriously finds its way into mitochondria through passive diffusion. In contrast, this study supports the hypothesis that the highly efficient transport of iron toward ferrochelatase in erythroid cells requires a direct interaction between transferrin-endosomes and mitochondria (the "kiss-and-run" hypothesis). Using a novel method (flow sub-cytometry), we analyze lysates of reticulocytes after labeling these organelles with different fluorophores. We have identified a double-labeled population definitively representing endosomes interacting with mitochondria, as demonstrated by confocal microscopy. Moreover, we conclude that this endosome-mitochondrion association is reversible, since a "chase" with unlabeled holotransferrin causes a time-dependent decrease in the size of the double-labeled population. Importantly, the dissociation of endosomes from mitochondria does not occur in the absence of holotransferrin. Additionally, mutated recombinant holotransferrin, that cannot release iron, significantly decreases the uptake of Fe by reticulocytes and diminishesFe incorporation into heme. This suggests that endosomes, which are unable to provide iron to mitochondria, cause a "traffic jam" leading to decreased endocytosis of holotransferrin. Altogether, our results suggest that a molecular mechanism exists to coordinate the iron status of endosomal transferrin with its trafficking. Besides its contribution to the field of iron metabolism, this study provides evidence for a new intracellular trafficking pathway of organelles.

Health and disease can only be distinguished by accurate and reliable reference values of a particular laboratory test. It is now a proven fact that there is considerable variation in hematology reference intervals depending on the demographic and preanalytical variables. There are evidences that values provided by manufacturers do not have appropriate application for all populations. Moreover, reference ranges provided by different laboratory manuals and books also do not solve this problem. We are presenting here normal reference ranges of Malaysian population. These values were determined by using Sysmex XE-2100 and ACL 9000 hematology and coagulation analyzers. Results from this study showed that there were considerable differences in the reference values from manufacturers, western population or laboratory manuals compared with those from the local population.

Pre-menopausal women have a lower risk of cardiovascular disease compared to postmenopausal women. Cardiovascular disease is more age dependent in women than in men. The association of platelet activation and cardiovascular thrombotic events is well established. Standardized techniques were used to evaluate platelet activation markers by flow cytometry, using 3-color analysis (CD 61PerCP, CD 62P, and PAC-1) in 49 postmenopausal (mean ± SD age, 56.16 ± 33.51 years) and 42 pre-menopausal (age, 39.38 ± 7.07 years) women. Results of our study showed a significant increase in CD 62P in postmenopausal women as compared to the pre-menopausal group (2.66 ± 4.26% vs. 0.52 ± 2.71%, P < 0.001). Similarly, PAC-1 was significantly increased in post-menopausal women (21.54 ± 2.48% vs. 3.70 ± 2.31%, P < 0.001). Furthermore, there was a significant association of CD 62P with serum estradiol in both groups. PAC-1 was significantly associated with age in both groups. The results suggest the role of platelets in the increased incidence of thrombotic events and disease in post-menopausal women. Am.

Hepatitis C virus infection is a major health problem worldwide. The current study estimated seroprevalence of Hepatitis C virus (HCV) and evaluated associated factors among volunteer blood donors of the Northwest Frontier Province (NWFP), Pakistan. Of 1,131 volunteer blood donors enrolled, 46 (4.1%) were positive for anti-HCV antibodies. Multivariate logistic regression analysis revealed that positive donors were more likely to be 27-32 years old or >32 years old, have had 1-2 injections or >2 injections in the past year, or 1-5 intravenous (IV) drips or >5 I/V drips in the past 5 years. Positive donors had a family history of jaundice and were more likely to have been shaved (facial and armpit) by barbers. There was high prevalence of anti-HCV antibodies among blood donors of the NWFP. Public awareness programs should target the identified risk factors to prevent HCV transmission. We highlight the weakness of the health care system for blood donation, as it does not offer any record management for donors.

These results showed that long-term treatment with losartan shows similar pressure independent reduction in PWV as perindopril among Malay hypertensive subjects with a homogenous "AA" genotype for angiotensin II type 1 receptor and may serve as a suitable alternative to perindopril.