Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran

BACKGROUND: The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications. METHODS: Two hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH) D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD) measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires. RESULTS: Short stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 ± 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH) D below 23 nmol/l were detected. CONCLUSION: High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions

Multifactorial anticancer effects of digalloyl-resveratrol encompass apoptosis, cell-cycle arrest, and inhibition of lymphendothelial gap formation in vitro

BACKGROUND: Digalloyl-resveratrol (di-GA) is a synthetic compound aimed to combine the biological effects of the plant polyhydroxy phenols gallic acid and resveratrol, which are both radical scavengers and cyclooxygenase inhibitors exhibiting anticancer activity. Their broad spectrum of activities may probably be due to adjacent free hydroxyl groups. METHODS: Protein activation and expression were analysed by western blotting, deoxyribonucleoside triphosphate levels by HPLC, ribonucleotide reductase activity by 14 C-cytidine incorporation into nascent DNA and cell-cycle distribution by FACS. Apoptosis was measured by Hoechst 33258/propidium iodide double staining of nuclear chromatin and the formation of gaps into the lymphendothelial barrier in a three-dimensional co-culture model consisting of MCF-7 tumour cell spheroids and human lymphendothelial monolayers. RESULTS: In HL-60 leukaemia cells, di-GA activated caspase 3 and dose-dependently induced apoptosis. It further inhibited cell-cycle progression in the G1 phase by four different mechanisms: rapid downregulation of cyclin D1, induction of Chk2 with simultaneous downregulation of Cdc25A, induction of the Cdk-inhibitor p21(Cip/Waf) and inhibition of ribonucleotide reductase activity resulting in reduced dCTP and dTTP levels. Furthermore, di-GA inhibited the generation of lymphendothelial gaps by cancer cell spheroid-secreted lipoxygenase metabolites. Lymphendothelial gaps, adjacent to tumour bulks, can be considered as gates facilitating metastatic spread. CONCLUSION: These data show that di-GA exhibits three distinct anticancer activities: induction of apoptosis, cell-cycle arrest and disruption of cancer cell-induced lymphendothelial disintegration. British Journal of Cancer (2010) 102, 1361-1370. doi:10.1038/sj.bjc.6605656 www.bjcancer.com (C) 2010 Cancer Research U

New clinical syndromes in dermatology

Dermatologists are in the unique position to be able to diagnose serious systemic diseases through skin findings; in addition, cutaneous manifestations can be associated with internal symptoms and clarify the pathogenesis and treatment of challenging new syndromes. Calciphylaxix, now renamed Calcific Uremic Arteriolopathy, primarily affects patients with end-stage renal disease with concomitant hyperphosphatemia, increased calcium-phosphate product and hyperparathyroidism, skin biopsy and wound care are crucial parts of the diagnosis and treatment. Hyperhomocysteinemia may play a very important role in many cutaneous and systemic diseases including, chronic cutaneous wounds, systemic lupus erythematosus, Behcet's disease and psoriasis. Through a skin biopsy and biochemical analysis of the proteoglycans accumulation it may be possible to diagnose a new systemic mucinosis and prevent sudden death in patients with severe mitral valve prolapse. Nephrogenic Fibrosing Dermopathy is a newly described fibrosing disorder occurring in patients with end stage renal disease, the etiology and pathogenesis are still unknown, and the ultimate course of this disease has not been defined

Basal cell carcinoma of the areola in a man

Basal cell carcinomas (BCCs) that arise in sun-protected sites are quite uncommon. We report a case of BCC of the areola, which is extremely rare. Mohs micrographic surgery was used for the treatment. The etiologic factors of BCCs in sun-protected areas are discussed, and previous studies regarding the treatment modalities are reviewed

132 Can a Topical Antimicrobial Agent Penetrate a Bi‐Layered Cell Therapy and be Effective Against Methicillin‐Resistant Staphylococcus Aureus?

Background:  Bilayered cell therapy (BLCT) is a significant advancement in the field of wound healing. BLCT expresses multiple growth factors found in normal skin, and provides a biologically active matrix in chronic wounds. Antibiotic‐resistant bacterium continues to be a major problem in chronic wounds. The use of appropriate topical antimicrobial agents could be one of the first steps in prevention of wound infection, although their use with BLCT is limited due to reported toxicity to cultured keratinocytes. Objectives:  This study was designed to see whether a topical antimicrobial agent is able to permeate through the BLCT and inhibits the growth of Methicillin‐Resistant Staphylococcus Aureus (MRSA). Mupirocin was used because of its lack of toxicity to cultured keratinocytes. Methods:  MRSA (ATCC# 33591) strain was used for these studies. The entire surface of blood agar plates were covered with a high inoclum of MRSA. BLCT specimens were placed on the agar plates and mupirocin was then applied on the top surface. As a positive control, mupirocin was applied directly on the agar plate, while BLCT specimens alone were used as negative control. The plates were subsequently incubated for 24 hours after which the zones of inhibition were assessed. Results:  Placing mupirocin on top of BLCT gave a 41.9 ± 17.2 mm inhibition zone diameter. Although it was smaller than the inhibition zone diameter produced by direct administration of mupirocin (26.3 ± 9.4 mm), this difference was not statistically significant. BLCT by itself did not create a zone of inhibition. Conclusion:  Mupirocin is able to permeate BLCT and inhibit the bacterial growth underneath it. This study may have important clinical implications

143 The Effect of Various Antimicrobial Agents on Acinetobacter Baumannii: An In Vitro Evaluation

Background:  Acinetobacter baumannii has recently emerged as an important hospital‐acquired pathogen, especially in surgery, burn, and intensive care units. Due to its ability to develop resistance to antimicrobials, wound infection with A. baumannii is difficult to treat, and can lead to septicemia and even death. Use of appropriate topical antimicrobial agents in these circumstances could be one of the first steps in prevention of A. baumannii wound infection. Objectives:  In this study, we will discuss the in vitro effects of seven common topical antimicrobial creams and dressings on A. baumannii. Methods:  A. Baumannii ATCC# 6919 was subjected to sensitivity tests against mupirocin, silver sulfadiazine, mafenide acetate, a double antibiotic combination of polymyxin and bacitracin, a triple antibiotic combination of Neomycin, bacitracin and polymyxin, and two silver‐containing dressings. Zones of inhibition were measured after 24 hours incubation period. Results and Conclusion:  Of the evaluated antimicrobial agents, mafenide acetate was the most efficacious followed by mupirocin, triple and double antibiotic combinations in decreasing order. The silver‐containing dressings yielded a lesser zone of inhibition as compared to the previously mentioned, and no zone of inhibition was observed using silver sulfadiazine. Further in vivo studies on the effect of antimicrobial agents against A. Baumannii are necessary to substantiate these findings and determine the potential clinical relevance of these therapies