Antonios Kattamis

Statins, bone formation and osteoporosis: hope or hype?

Osteoporosis is a major health problem affecting both men and women. Statins, besides their action as lipid-lowering agents, seem to have additional pleiotropic properties, among them a beneficial effect on bone mineral density. The entirety of experimental and the majority of clinical studies as well as the only relevant meta-analysis suggest that statins have an anabolic effect on bone metabolism. Statins, osteoporosis and adipogenesis share the same pathway, RANKL/OPG. It would appear that an imbalance in this pathway could be responsible for the manifestation of some metabolic disorders such as diabetes mellitus, atherogenesis, multiple myeloma, osteoporosis. Possibly in the future, drugs which can intervene in this biochemical and pathophysiological cascade, like statins, in a variety of doses, could be used for the management of ectopic ossification syndromes and other bone disorders, even as an additive treatment. Until then, further large longitudinal randomized controlled studies for each statin separately are required to confirm this hypothesis.

Combined umbilical cord blood and bone marrow transplantation in the treatment of β-thalassemia major

The authors report on three children with beta-thalassemia major, class II, III, and III according to the Pesaro classification, with a body weight of 16, 62, and 50 kg, respectively, who received grafts using both umbilical cord blood (UCB) and bone marrow (BM) stem cells from their HLA-matched siblings. The number of UCB nucleated cells collected was 2x107/kg, 1.2x107/kg, and 2.5x107/kg, respectively, and was considered insufficient to secure engraftment. The authors increased the number of hematopoetic progenitors by harvesting BM from the same donors. All 3 patients showed prompt engraftment with neutrophil recovery on days 17, 18, and 17 post-transplant, respectively, and platelet recovery on days 19, 25, and 22 post-transplant, respectively. One patient had remarkably increased HbF of values 31, 19, and 12% at 3, 6, and 12 months post-transplant, respectively, which were accompanied by an increase in the Ggamma/Agamma ratio, suggesting UCB-derived hematopoetic reconstitution. All patients are alive and transfusion independent 23, 18, and 16 months post-transplant, respectively. For patients with homozygous beta-thalassemia who are at high risk of graft failure, either because of major prior alloimmunization or an insufficient amount of UCB stem cells, combined transplantation with UCB and BM could offer a quick and safe alternative herapy.

OXIDATIVE STRESS DISTURBANCES IN ERYTHROCYTES OF ß-THALASSEMIA

A prooxidant ± antioxidant balance is normally achieved in aerobic steady state. This balance may be distorted by oxidative stress caused by reactive oxygen species, which are generated in aerobic metabolism. The reactive oxygen species, which include superoxide anion radical, hydrogen peroxide, singlet molecular oxygen, hydroxyl, and nitric oxide radicals, are involved in a number of physiological processes, such as in ̄ ammation, carcinogenesis, radiation damage, photobiological reactions, and aging. Prooxidants generated in the process of oxidative stress are controlled by three main types of defensive mechanisms: prevention, intervention, and repair. The type of defense is mainly associated with the type and half-life of the prooxidant. Prevention is mainly achieved by the combined function of antioxidants and enzymes. Intervention is the domain of chain-breaking antioxidants, such as tocopherols, and repair occurs mainly through enzymatic mechanisms [1, 2]. To this end, evolution has provided sets of complementary enzyme systems, which in some cases are under concerted control; this is of fundamental importance for repair of DNA damage and repair of phospholipids by reacylation pathways. The human plasma contains a variety of nonenzymatic antioxidants, which include the water-soluble ascorbate, glutathione (GSH), urate, and bilirubin and the lipid-soluble ®and ° -tocopherol, ®and ̄ -carotene, lycopene, lutein, ubiquinol-10, and zeaxanthin. The plasma levels of these antioxidants vary signi® cantly and are greatly reduced in case of oxidative stress. Upon oxidation these micronutrients regenerate by coupling to non-radical, reducing systems, such as glutathione/glutathione disul® de, dihydrolipoate/lipoate, or NADPH/NADPC and NADH/NADC [2].

Endocrine problems in ex-thalassemic patients.

Twenty-seven patients (14 females) that were successfully transplanted from a relative matched donor were included in the study. Conditioning regimen included cyclophosphamide (14±16 mg/kg) and busulfan (150±200 mg/kg). ALG was used in most cases. GvHD prophylaxis included cyclosporine, and short course of methotrexate. Five patients received a 2nd transplantation after rejecting their ®rst graft. The mean age at transplantation was 9.3 yr (range: 2.8±16.4). The patients were evaluated at a mean time of 32.7 months (range: 13±68) post-BMT. Serum ferritin levels were estimated before BMT and at the time of evaluation. 2. Results

Pregnancy Complications in a-Thalassemia (Hemoglobinopathy H): A Case Study

Thalassemia intermedia (TI) is a clinical definition which represents a wide spectrum of thalassemia genotypes but mainly includes patients who do not require or only occasionally require transfusion. An uncommon case of a 32-year-old Greek woman, para 1, at the 22nd week + day 3 of gestation with thalassemia intermedia (she was splenectomized), where her pregnancy was complicated with portal vein thrombosis, splenic thrombosis, and partial HELLP, is described. This is a generally uncommon event in thalassemia intermedia. She had no transfusion as her hematologist consulted and she took anticoagulation therapy. Thus, we present for the first time in the literature a case of HbH a-thalassemia pregnant woman whose pregnancy was complicated with portal vein thrombosis, splenic vein thrombosis, and partial HELLP; she was treated with anticoagulation therapy and she had a successful outcome.