Neurodevelopmental outcome of infants with birth asphyxia treated with magnesium sulfate

BACKGROUND: A neuroprotective effect of MgSO(4) has been shown in some animal models of perinatal hypoxic-ischemic brain damage. The aim of the present paper was to determine whether postnatal MgSO(4) infusion (250 mg/kg per day i.v. for 3 days, in combination with dopamine) is safe in infants with severe birth asphyxia, and also observe effects on neurodevelopmental outcome at 18 months. METHODS: Inclusion criteria were clinical history consistent with perinatal asphyxia; gestational age at least 37 weeks; 5 min Apgar score < or =6; failure to initiate spontaneous respiration within 10 min after birth; and symptoms of encephalopathy. On each day MgSO(4) was infused over 1 h in combination with dopamine (5 microg/kg per min). Changes in vital signs, clinical course of encephalopathy, laboratory variables, and adverse events were monitored. Infants were followed for 18 months. RESULTS: Thirty infants were studied. Mean birthweight was 2878 g; mean gestational age, 39.6 weeks, and median 5 min Apgar score, 3. All required endotracheal intubation for resuscitation. Median age at MgSO(4) initiation was 5 h. All infants had moderate or severe hypoxic-ischemic encephalopathy. Mean serum Mg(2+) concentration remained at least 1.3 mmol/L. MgSO(4) caused no change in physiological variables including mean arterial pressure. Two infants died as neonates, while six of 28 survivors had severe neurodevelopmental disability at 18 months; the remaining 22 had no neurodevelopmental disability. CONCLUSION: Postnatal infusion of MgSO(4) with dopamine caused no change in physiological variables. Deaths and severe sequelae were less frequent than in reported cases with the same grade of hypoxic-ischemic encephalopathy severity, and this treatment may improve neurodevelopmental outcome in infants with severe birth asphyxia.     

Further evidence for the presence of subepithelial nerve cells in the rat ileum—an immunohistochemical study

Earlier we observed electronmicroscopically an unidentified but neuron-like subepithelial cell in the crypts of the rat ileum. We have now studied some immunocytochemical characteristics of similar cells in the fluorescence microscope by indirect immunofluorescence. Three markers for neuronal tissues were used: 1) Monoclonal Thy-1-antibodies, demonstrated previously to recognize surface antigens of thymus-derived cells and nervous tissue; 2) Tetatus toxin, which binds to the G_TI ganglioside receptor of nerve cells, and to some other neuronal receptor; and 3) Anti-Protein I-IgG, which is monospecific for Protein I located in synaptic vesicle membranes. The various antisera used for secondary incubations all reacted with leucocytes and other connective tissue cells in the villous cores. When the specific primary antisera of Thy-1 and Protein I, and tetanus toxin, were included, a small number of spindle-shaped cells with two processes, extending just beneath the basal lamina of the epithelium, was observed. These cells had a similar location and appearance as the neuron-like cells observed electronmicroscopically and may be identical with these cells. These results give further evidence that cells with neuron-like characteristics are present in the mucous layer of the small intestine.     

A Case of Ménétrier's Disease Accompanied by Severe Hypogammaglobulinemia

We describe a case of Ménétrier's disease accompanied by severe hypoproteinemia with marked decrease of gamma globulin. Roentogenograms and endoscopic findings of the upper gastrointestinal tract demonstrated enlarged gastric rugae and multiple small protuberances of the duodenal mucosa. Histological findings of gastric biopsy specimens showed mucosal thickening and hypertrophy. Plasminogen activator activities were increased in both gastric and jenunal mucosal biopsy specimens. Severe hypoproteinemia was proven by the Gordon test and by determination of ptotein content of gastric Juice to be due to protein loss into the gastric lumen.     

Adenylate cyclase induces intracellular calcium increase in single human epidermal keratinocytes measured by fluorescence microscopy using Fura 2-AM

Intracellular calcium ([Ca2+]i) is an important second messenger of extracellular signals to induce various cellular responses. Extracellular and intracellular Ca2+ are considered to be important for cellular differentiation and proliferation of epidermal keratinocytes. Several mechanisms which increase [Ca2+]i have been demonstrated in various tissues, but in epidermal keratinocytes these mechanisms are poorly understood. In epidermal keratinocytes the adenylate cyclase-cyclic AMP response is thought to regulate cell proliferation and differentiation. However, the series of reactions which follow the cyclic AMP response remain unknown. Beta-adrenergic agonists increase [Ca2+]i in cultured epidermal keratinocytes, and we have therefore studied whether stimulation of keratinocyte adenylate cyclase could induce [Ca2+]i increase, by using fluorescence microscopy with Fura 2-AM. Adenosine and histamine, which are known to be keratinocyte adenylate cyclase receptor agonists, induced transient [Ca2+]i increase, as did epinephrine. In addition, forskolin, a direct adenylate cyclase activator, and dibutyryl-cyclic AMP also induced an increase in [Ca2+]i. In a calcium-free medium epinephrine, adenosine, histamine and dibutyryl-cyclic AMP induced an increase in [Ca2+]i. These results suggest that cyclic AMP in human epidermal keratinocytes regulates [Ca2+]i, which is released from intracellular stores.     

Enhanced arterial intimal thickening after balloon catheter injury in diabetic animals accompanied by PDGF β-receptor overexpression of aortic media

Abstract. Cultured aortic smooth muscle cells (SMC) of diabetic rats and rabbits, which overexpress platelet-derived growth factor (PDGF) β -receptor compared with controls, have a unique phenotype. In this study we report on the PDGF β -receptor overexpression in aortas of diabetic animals and the increased intimal thickening of carotid arteries in diabetic rabbits after balloon catheter injury compared with that in controls. In diabetic aortas with no treatments of balloon catheter injury, intimal thickening was not observed in spite of the overexpression of PDGF β -receptor, indicating that the growth property of medial SMC in diabetic aortas was changed before the intimal thickening could take place. PDGF is known to be the main contributor to the intimal thickening induced by balloon catheter injury, which is one of several forms of arterial injuries. Intimal thickening after balloon catheter injury in diabetic rabbits increased compared with that in controls. These results imply that PDGF β -receptor overexpression of SMC in medial layers plays an important role in intimal thickening in the formation of advanced diabetic macroangiopathy.