Inhibition of Na(+),K(+)-ATPase in the hypothalamus, pons and cerebellum of the offspring rat due to experimentally-induced maternal hypothyroidism.

Neurodevelopment is known to be particularly susceptible to thyroid hormone insufficiency and can result in extensive structural and functional deficits within the central nervous system (CNS), subsequently leading to the establishment of cognitive impairment and neuropsychiatric symptomatology. The current study evaluated the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism (as a suggestive multilevel experimental approach to the study of hypothyroidism-induced changes that has been developed and characterized by the authors) on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a CNS region-specific manner. The activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase in the offspring hypothalamus, cerebellum and pons were assessed. The study demonstrated that maternal exposure to PTU (0.05% w/v in the drinking water) during the critical periods of neurodevelopment can result in an inhibition of hypothalamic, pontine and cerebellar Na(+),K(+)-ATPase; a major marker of neuronal excitability and metabolic energy production as well as an important regulator of important systems of neurotransmission. On the other hand, no significant changes in the activities of the herein offspring CNS regions' AChE and Mg(2+)-ATPase were recorded. The observed Na(+),K(+)-ATPase inhibition: (i) is region-specific (and non-detectable in whole brain homogenetes), (ii) could constitute a central event in the pathophysiology of clinically-relevant hypothyroidism-associated developmental neurotoxicity, (iii) occurs under all examined experimental schemes, and (iv) certainly deserves further clarification at a molecular and histopathological level. As these findings are analyzed and compared to the available literature, they also underline the need for the adoption and further study of Na(+),K(+)-ATPase activity as a consistent neurochemical marker within the context of a systematic comparative study of existing (and novel) simulation approaches to congenital and early age hypothyroidism.

Hereditary pancreatitis: dilemmas in differential diagnosis and therapeutic approach.

INTRODUCTION: Hereditary pancreatitis (HP) is a rare, heterogeneous familial disease and should be suspected in any patient who has suffered at least two attacks of acute pancreatitis for which there is no underlying cause and unexplained chronic pancreatitis with a family history in a first- or second-degree relative. Genetic factors have been implied in cases of familial chronic pancreatitis. The most common PRSS1 mutations worldwide are the R122H and N29I variants. CLINICAL FEATURES: HP usually appears with an acute, a recurrent acute, and a chronic phase, referring to the inflammation of the pancreas and the symptoms' onset and duration. The clinical features of acute pancreatitis begin in childhood and last less than 6 months. HP carries a 50-70-fold increased risk of pancreatic cancer within 7-30 years of disease onset. HP diagnosis is defined by the presence of a detected cationic trypsinogen gene mutation (with or without clinical or radiological manifestations of chronic pancreatitis) or when the patient's family satisfies the requirements of the EUROPAC. TREATMENT: With regard to the therapeutic approach, pancreatic enzyme replacement therapy and analgesics are offered to control pain. In addition, endoscopic and surgical intersections are reserved for all relevant complications. Unfortunately, surgical removal of affected pancreatic tissue does not necessarily guarantee the patient's long-term survival. Furthermore, the prognostic factors and the efficacy of extended resection remain controversial.