ABSTRACT
Hypokalemia and hypomagnesemia are frequently observed in patients with chronic alcoholism. However, the involvement of deranged cortisol regulation in patients with those conditions has not been reported. A 63-year-old Japanese male with chronic alcoholism was referred to the Department of Diabetes, Endocrinology and Metabolism for examination and treatment of hypokalemic periodic paralysis. Laboratory findings showed hypokalemia (2.3 mmol/l), as well as a high level of urinary excretion of potassium and hypomagnesemia (1.2 mg/dl), whereas urinary excretion of magnesium was undetectable. Potassium infusion treatment recovered that level in serum to 4.1 mmol/l, though it decreased to 2.2 mmol/l following discontinuation. A dexamethasone suppression test and urinary cortisol level showed corticotropin-dependent hypercortisolemia. However, gadolinium-enhanced MRI revealed no evidence of pituitary adenoma. The patient recovered from hypokalemia following an administration of magnesium in addition to potassium, which was accompanied by potassium over-excretion improvement. After being discharged, serum potassium level was maintained within a normal range with only magnesium infusion treatment. Furthermore, alcohol intake was reduced from 160 to 20 g/day and an endocrinological re-examination after that restriction showed normal cortisol regulation. The patient was diagnosed with pseudo-Cushing's syndrome induced by alcohol abuse. Serum potassium level was maintained within a normal range even after discontinuation of magnesium supplementation. Our findings in this case indicate that pseudo-Cushing's syndrome in conjunction with hypomagnesemia may be involved in development of hypokalemia in patients with chronic alcoholism.
ABSTRACT
Mucopolysaccharidosis type VII (MPSVII) is a lysosomal storage disease resulted from a deficiency of the enzyme beta-glucuronidase (GUSB), which is necessary for degradation of glycosaminoglycans (GAGs). The deficiency of GUSB causes progressive accumulation of GAGs and subsequent lysosomal distension in multiple tissues, including the central nervous system (CNS). In murine experiments, bone marrow transplant, enzyme replacement, viral vectors, and genetically modified cells were successfully used for correction of the visceral accumulation of GAGs, but little improvement was seen in the brain, because these therapeutic agents cannot cross the blood-brain barrier (BBB). Although direct intracerebral injection of GUSB-encoding viral vectors has been developed to bypass the BBB, the possibility of tumor formation and the toxicity of over-expressed GUSB have been reported. In this study, we generated immortalized human amniotic epithelial (IHAE) cells to maintain the effect of implantation, and encapsulated these cells to prevent harmful immunological response and tumor formation and to regulate the level of GUSB expression within the host. Moreover, we generated IHAE cells that over-express and secrete human GUSB following transduction with an adenoviral vector encoding human GUSB. Therapeutic efficacy for MPSVII was evaluated in and ex vivo experiments using these encapsulated genetically engineered GUSB-encoding IHAE cells. We confirmed that encapsulated genetically engineered IHAE cells could secrete significant amounts of GUSB outside the capsule in vitro and into the cerebral parenchyma of C3H mice seven days after the capsule implantation. Thus, encapsulation cell therapy using genetically engineered IHAE cells is an effective armamentarium for the treatment of MPSVII.
