Physiologic importance of glutamine.
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Biomedical subjects
Publications and source records attributed to F Ghishan.
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Four-day fasting in the conscious dog is associated with enhanced ammoniagenesis in both the gut and kidneys and a switch in the hepatic glutamine balance from net uptake to that of net production. In the present study we examined the role that the rise in portal venous ammonium ions plays in regulating nitrogen metabolism in vivo. Three groups of 18- to 24-h fasted conscious dogs with catheters surgically implanted in the femoral artery and in the hepatic, portal, and renal veins for 17-21 days were studied. On the day of the study, one group (n = 6) received intraportal ammonium acetate at 3.0 mumol.kg-1.min-1 intended to result in portal venous ammonium ion levels slightly above those seen in the 4-day fasted dog. Another group (n = 5) received an equimolar infusion of sodium acetate, and a third group (n = 6) received saline (0.9%) and acted as controls. Organ balances across the liver, extrahepatic splanchnic tissues (gut), and kidneys were estimated by the arteriovenous differences multiplied by blood flows. All of the load of ammonium acetate infused intraportally was taken up by the liver. As a result there was an immediate switch in hepatic glutamine balance from that of net uptake to net production similar to that seen in the 4-day fasted dog. Simultaneously, net hepatic production of urea nitrogen doubled. These occurred with no change in acid-base balance or no change in circulating arterial or portal venous levels of insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)
The developmental aspects of calcium uptake by intestinal Golgi vesicles was determined using highly purified Golgi vesicles from enterocytes of suckling (2 wk old), weanling (3 wk old), and adolescent (6 wk old) rats. Calcium uptake by Golgi vesicles at all age groups represented transport into the intravesicular space as evident by temperature dependency and by calcium ionophore A23187-induced calcium efflux studies. Calcium uptake was driven by ATP at all age groups, however, maximal uptake at 15 min was significantly greater in Golgi vesicles of adolescent rats compared to mean values in Golgi vesicles of suckling rats (p less than 0.01). Calcium uptake in the absence of ATP was minimal. The requirement for the adenine base and the hydrolysis of the beta-gamma-phosphodiester was tested by replacement of ATP in the incubation media by CTP and the nonhydrolyzable ATP analogue, adenylyl-(beta-gamma-methylendiphosphonate). Both agents had no stimulatory effect on calcium uptake. Calcium uptake was linear up to 40 s. Kinetic parameters of calcium uptake at free calcium concentrations of 0.04 to 1.0 microM showed a maximal transport capacity of 0.99 +/- 0.05, 0.55 +/- 0.04, and 0.29 +/- 0.03 nmol/mg protein/15 s for adolescent, weanling, and suckling rats, respectively. Km values were 0.16 +/- 0.02, 0.12 +/- 0.03, and 0.07 +/- 0.02 microM for adolescent, weanling and suckling rats, respectively. Km and Vmax values were significantly different between adolescent and suckling rats (p less than 0.01). The calcium regulatory protein calmodulin has no effect on calcium uptake by Golgi vesicles. Vitamin D deficiency in all age groups decreased ATP-dependent calcium uptake. Administration of 1,25-(OH)2 vitamin D3 8 h before death enhanced ATP-dependent calcium uptake in all age groups studied. This enhancement was the result of increase in maximal transport capacity of ATP-dependent calcium uptake. This study demonstrates a vitamin D-regulated ATP-driven calcium uptake by intestinal Golgi vesicles at all age groups including the suckling period. This transport system shows developmental patterns in regard to its kinetic parameters.
Acetaminophen is widely used in children of all ages, and overdosage from this medication is common. Although severe hepatotoxicity from over-dosage occurs in adults, acetaminophen seems to have a wide margin of safety in younger children. This has been ascribed to altered pharmacokinetics in this age group. We report two cases in which severe acetaminophen-induced hepatoxocity occurred in two infants. Neither infant reportedly received potentially toxic dosages, by history, but toxic drug levels were present in both.
A patient with common variable immunodeficiency disease is described with severe colitis confined to the rectosigmoid region. Inflammation was extensive in the regions involved and exhibited a character that we believe is most unusual. Inflammation was transmural in the regions involved. Macrophages were the major inflammatory cells, and no granulomas or giant cells were seen. Although the disorder seemed distinct from either ulcerative colitis or Crohn's disease, the colitis responded favorably to oral azulfidine, prednisone, and to steroid enemas.
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