Zinc deficiency aggravates abnormal glucose metabolism in thalassemia major patients.

BACKGROUND: The aim was to determine whether reduced serum zinc level has a contributory effect on impairment of insulin secretion in beta-thalassemic patients with transfusion-induced iron overload. MATERIAL/METHODS: Seventy thalassemia patients who received deferoxamine chelation therapy and 69 healthy individuals as the control group were evaluated. A standard oral glucose tolerance test (OGTT) was performed and blood samples for measurement of serum ferritin, zinc, and insulin concentrations were obtained. RESULTS: Although the fasting serum insulin concentrations were quite similar between the patient and the control groups, serum insulin levels were significantly lower in the thalassemia patients one hour and two hours after oral glucose load ingestion compared with the healthy controls. Among the thalassemic adults, zinc deficiency (present in 37% of patients) resulted in significantly lower fasting and 1-hour post-OGTT serum insulin concentrations. The serum zinc level in patients with impaired OGTT was also considerably lower than in patients with normal OGTT. CONCLUSIONS: These data support the assumption that zinc deficiency might lead to an exacerbation of the inability of the pancreas to secrete sufficient amounts of insulin in response to glucose stimulation in beta-thalassemia patients. We suggest that serum zinc levels be routinely monitored in these patients as it might provide useful complementaly information regarding glucose metabolism.

Matrix metalloproteinase 2 secretion in WEHI 164 fibrosarcoma cells is nitric oxide-related and modified by morphine.

Matrix metalloproteinases (MMP) are ubiquitous enzymes involved in extracellular matrix remodeling, and as a consequence in a number of physiological and pathological states, including development, wound healing and cancer. A crucial feature of cancer progression and metastasis is the disruption of extracellular matrix, and spreading of proliferating cancer cells. Modulation of MMP is a main target of cancer research. Using the mouse fibrosarcoma cell line WEHI 164, producing high amounts of MMP-2, we investigated whether we could modulate its production. We report that MMP-2 is under the control of nitric oxide (NO)/nitric oxide synthase (NOS) system. In addition, we show that NOS activity is controlled by opioids in a non-opioid receptor-related manner. Finally, we provide evidence that morphine, when administrated at low, non-toxic concentrations (<10(-9) M) attenuates MMP-2 activity. We conclude that, as morphine is able to decrease metalloproteinase activity via the NO/NOS system, it may have a place in the treatment of several sarcomas including fibrosarcoma.