Effects of total parenteral nutrition on exocrine pancreatic secretion

The effects of various components of TPN on the volume output, bicarbonate, and amylase concentration of a postoperative pancreatic fistula were studied.
Concentrated glucose solutions caused a significant decrease in the volume output and amylase concentration while fat solution increased the volume secretion and amylase concentration. Amino acids solution did not significantly effect the fistula output.
An appropriate composition of TPN is of value in the treatment of pancreatic fistula by inhibiting secretion and protecting against major loss of fluid protein and electrolyte.     

Afferent connections to the amygdaloid complex of the rat and cat. I. Projections from the thalamus.

By the use of the retrograde transport of horseradish peroxidase (HRP), the projections from the thalamus to the amygdala were investigated in the rat and cat, with main emphasis on the former species. HRP was injected stereotactically by microiontophoresis in the various amygdaloid nuclei. Several control procedures including the use of different approaches for the introduction of the micropipette were undertaken to eliminate the possibility of misinterpretation due to uptake of the protein by adjacent structures or fibers en passant. The paraventricular and paratenial nuclei of the thalamus were found to project throughout the entire amygdaloid complex. The medial geniculate complex and the basal nucleus of the ventromedial complex (the thalamic taste relay) mainly project to the centromedial part of the amygdala. The basolateral nucleus is the main recipient of a hitherto undescribed bilateral thalamo-amygdaloid pathway originating in the interanteromedial nucleus. The parafasciculare nucleus projects to the central nucleus of the amygdala; in the cat mainly to the lateral subdivision of the central nucleus. The findings are discussed in relation to previous anatomical and electrophysiological studies centered on the amygdaloid complex. Special reference is made to the possible role of the thalamo-amygdaloid connections in the conveyance of sensory information to the amygdala.     

Excitatory action of GABA on immature neurons is not due to absence of ketone bodies metabolites or other energy substrates

Brain slices incubated with glucose have provided most of our knowledge on cellular, synaptic, and network driven mechanisms. It has been recently suggested that γ-aminobutyric acid (GABA) excites neonatal neurons in conventional glucose-perfused slices but not when ketone bodies metabolites, pyruvate, and/or lactate are added, suggesting that the excitatory actions of GABA are due to energy deprivation when glucose is the sole energy source. In this article, we review the vast number of studies that show that slices are not energy deprived in glucose-containing medium, and that addition of other energy substrates at physiologic concentrations does not alter the excitatory actions of GABA on neonatal neurons. In contrast, lactate, like other weak acids, can produce an intracellular acidification that will cause a reduction of intracellular chloride and a shift of GABA actions. The effects of high concentrations of lactate, and particularly of pyruvate (4-5 mm), as used are relevant primarily to pathologic conditions; these concentrations not being found in the brain in normal "control" conditions. Slices in glucose-containing medium may not be ideal, but additional energy substrates neither correspond to physiologic conditions nor alter GABA actions. In keeping with extensive observations in a wide range of animal species and brain structures, GABA depolarizes immature neurons and the reduction of the intracellular concentration of chloride ([Cl(-)](i)) is a basic property of brain maturation that has been preserved throughout evolution. In addition, this developmental sequence has important clinical implications, notably concerning the higher incidence of seizures early in life and their long-lasting deleterious sequels. Immature neurons have difficulties exporting chloride that accumulates during seizures, leading to permanent increase of [Cl(-)](i) that converts the inhibitory actions of GABA to excitatory and hampers the efficacy of GABA-acting antiepileptic drugs.     

Stiripentol, a putative antiepileptic drug, enhances the duration of opening of GABA-A receptor channels

PURPOSE: Stiripentol (STP) is currently an efficient drug for add-on therapy in infantile epilepsies because it improves the efficacy of antiepileptic drugs (AEDs) through its potent inhibition of liver cytochromes P450. In addition, STP directly reduces seizures in several animal models of epilepsy, suggesting that it might also have anticonvulsive effects of its own. However, its underlying mechanisms of action are unknown. METHODS: We examined the interactions of STP with gamma-aminobutyric acid (GABA) transmission by using patch-clamp methods in CA3 pyramidal neurons in the neonatal rat. RESULTS: STP markedly increased miniature inhibitory postsynaptic current (mIPSC) decay-time constant in a concentration-dependent manner. The prolongation of mIPSC duration does not result from an interaction with GABA transporters because it persisted in the presence of GAT-1 inhibitors (SKF-89976A and NO-711). An interaction with benzodiazepine or neurosteroid binding sites also was excluded because STP-mediated increase of decay time was still observed when these sites were initially saturated (by clobazam, zolpidem, or pregnanolone) or blocked (by flumazenil or dehydroepiandrosterone sulfate), respectively. In contrast, saturating barbiturate sites with pentobarbital clearly occluded this effect of STP, suggesting that STP and barbiturates interact at the same locus. This was directly confirmed by using outside-out patches, because STP increased the duration and not the frequency of opening of GABAA channels. CONCLUSIONS: At clinically relevant concentrations, STP enhances central GABA transmission through a barbiturate-like effect, suggesting that STP should possess an antiepileptic effect by itself.     

Electrical stimulation of preganglionic nerve increases tyrosine hydroxylase activity in sympathetic ganglia.

The effect of synaptic stimulation on tyrosine hydroxylase [tyrosine 3-monooxygenase: L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] activity in the rat superior cervical ganglion was studied. The preganglionic cervical sympathetic trunk was stimulated unilaterally at 10 Hz for 30 min. Forty-eight hours later tyrosine hydroxylase activity was 33% higher on the stimulated than on the control side. The enzyme activity restimulated than on the control side. The enzyme activity remained elevated in the stimulated ganglia for 2 days. No change was observed in total ganglion protein. Comparable increases in tyrosine hydroxylase activity were observed in anesthetized and conscious animals.     

Intra-amygdaloid injections of kainic acid: regional metabolic changes and their relation to the pathological alterations

Kainic acid was injected unilaterally in the amygdala of the rat. Following various delays, 2-deoxy-D-[14C]glucose was given intravenously. Autoradiographs of frontal brain sections showed increased glucose uptake in a number of cerebral structures as compared with controls. Most of these structures belong to, or are closely related to, what is traditionally called the 'limbic system'. The structures that show an increased glucose consumption subsequent to kainic acid injections are, with few exceptions, identical to those that are sensitive to the toxic effect that kainic acid exerts on structures distant to the site of injection. The findings are discussed in relation to the hypothesis that the latter effect is secondary to the epileptogenic properties of kainic acid.     

Association of lamivudine resistance in recurrent hepatitis B after liver transplantation with advanced hepatic fibrosis.

BACKGROUND: Orthotopic liver transplantation (OLT) in patients with hepatitis B virus (HBV) infection is known to be associated with a high recurrence rate and poor prognosis. Lamivudine, a nucleoside analogue, is a potent inhibitor of HBV replication, but it is associated with a 14-39% rate of resistance. METHODS: We report on four patients who underwent OLT for HBV infection. In all cases, the HBV infection recurred in the grafted liver and was treated with lamivudine (100 mg daily) on a compassionate-use basis. The patients were monitored closely for serum liver enzymes, hepatitis B surface antigen and HBV DNA (by hybridization). Liver biopsy was performed before and after lamivudine therapy. HBV DNA was amplified from serum for each patient and sequenced through a conserved polymerase domain, the tyrosine-methionine-aspartate-aspartate (YMDD) locus. RESULTS: All four patients exhibited lamivudine resistance 9-20 months after initiation of the drug. In all patients with a clinically mild disease, liver histology findings (12-24 months after lamivudine therapy) showed progressive fibrosis as compared to biopsies performed before lamivudine therapy, with a significant increase (> or =2 points) in the Knodell score in three patients. Moreover, two patients exhibited worsening of the necroinflammatory process. A mutation at the YMDD motif of the HBV polymerase gene was detected in all cases. CONCLUSIONS: Lamivudine resistance frequently occurs in patients with recurrent HBV infection after OLT and is associated with advanced hepatic fibrosis and necroinflammatory process. A combination of antiviral therapies may be necessary.     

Neocortex in the hippocampus: An anatomical and functional study of CA1 heterotopias after prenatal treatment with methylazoxymethanol in rats

Migration disorders cause neurons to differentiate in an abnormal heterotopic position. Although significant insights have been gained into the etiology of these disorders, very little is known about the anatomy of heterotopias. We have studied heterotopic masses arising in the hippocampal CA1 region after prenatal treatment with methylazoxymethanol (MAM) in rats. Heterotopic cells were phenotypically similar to neocortical supragranular neurons and exhibited the same temporal profile of migration and neurogenesis. However, they did not express molecules characteristic of CA1 neurons such as the limbic-associated membrane protein. Horseradish peroxidase injections in heterotopia demonstrated labeled fibers not only in the neocortex and white matter but also in the CA1 stratum radiatum and stratum lacunosum. To study the pathophysiological consequences of this connectivity, we compared the effects of neocortical and limbic seizures on the expression of Fos protein and on cell death in MAM animals. After metrazol-induced seizures, Fos-positive cells were present in CA1 heterotopias, the only hippocampal region to be activated with the neocortex. By contrast, kainic acid-induced seizures caused a prominent delayed cell death in limbic regions and in CA1 heterotopias. Together, these results suggest that neocortical heterotopias in the CA1 region are integrated in both the hippocampal and neocortical circuitry. J. Comp. Neurol. 394:520–536, 1998. © 1998 Wiley-Liss, Inc.