Elevated Serum γ-Aminobutyric Acid Levels in Children with Reyeʼs Syndrome

Minuk, Gerald Y.; Sarjeant, E J; Buchan, Kevin

doi:10.1097/00005176-198508000-00005

Cited by 8 publications

(6 citation statements)

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“…Although overlap occurred, in accordance with other published data (17)(18)(19), patients with cirrhosis of the liver (Group I) had higher serum GABA levels (1.12 f 0.26 pM, mean k S.E.) than patients in the other two groups (Group 11, 0.41 & 0.05 p M , p < 0.005; Group 111, 0.34 f 0.03 p M , p < 0.02) ( Figure 1).…”

Section: Arterial Blood Pressure Recordingssupporting

confidence: 92%

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Is the hypotension of cirrhosis a GABA-mediated process?

Minuk

MacCannell

1988

Hepatology

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Systolic and diastolic blood pressures were recorded in 176 ambulant patients with chronic liver disease, including 36 patients with compensated cirrhosis (Group I), 119 patients with noncirrhotic chronic liver disease (Group II) and 21 patients with benign structural or functional liver disease (Group III). Group I patients had significantly lower systolic (113.0 +/- 2.2 mm Hg, mean +/- S.E.) and diastolic (65.3 +/- 1.7 mm Hg) pressures than Group II patients (125.8 +/- 3.5 and 76.6 +/- 1.5 mm Hg, respectively (p less than 0.0001) or Group III patients (125.1 +/- 3.4 and 77.5 +/- 2.4 mm Hg, respectively) (p less than 0.0001). Serum levels of GABA, a potent amino acid neurotransmitter with known vasodilatory effects in vitro, were higher in Group I patients (1.12 +/- 0.26 microM, mean +/- S.E.) than in Group II patients (0.41 +/- 0.05 microM) (p less than 0.005) or Group III patients (0.34 +/- 0.03 mM) (p less than 0.05). A constant infusion of GABA into the systemic circulation of six adult dogs, at rates required to achieve serum GABA levels within one order of magnitude of those observed in humans with cirrhosis, resulted in a 17.0 +/- 4.3 mm Hg decrease in systolic pressure (p less than 0.05) and a 10.8 +/- 3.7 mm Hg decrease in diastolic pressure (p less than 0.05). Control amino acids were not vasoactive. The results of this study suggest that, in addition to other vasoactive compounds, a GABA-mediated process might contribute to the hypotension observed in patients with compensated cirrhosis.

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Section: Arterial Blood Pressure Recordingssupporting

confidence: 92%

“…Serum gaba Determinations. Fluorometric ion-exchange chromatography was used to determine serum GABA levels (19,25 24 hr, were anesthetized with 30 mg per kg of sodium pentobarbital, intubated and ventilated with room air using a Harvard respiration pump. Arterial blood gases were checked periodically to ensure adequate ventilation.…”

Section: Patients)mentioning

confidence: 99%

Is the hypotension of cirrhosis a GABA-mediated process?

Minuk

MacCannell

1988

Hepatology

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“…Serum biomarkers and observed associations with HE or MHE are summarized in Table 2 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). IL-6 and TNF-alpha were the most frequently studied biomarkers, with all remaining markers evaluated in 2 or fewer studies.…”

Section: Resultsmentioning

confidence: 99%

“…Study content is summarized in Table 1. The studies included 6 pediatric and 9 mixed cohorts (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Patients in these studies were categorized as either MHE or HE and were compared to controls with and without liver disease.…”

Section: Resultsmentioning

confidence: 99%

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Novel Serum Biomarkers Associated With Pediatric Hepatic Encephalopathy: A Systematic Review

Krishnan

Rao

Chang

et al. 2023

Journal of Pediatric Gastroenterology &Amp; Nutrition

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Background:The pathophysiology of pediatric hepatic encephalopathy (HE) is not well understood. Various serum biomarkers associated with HE may provide insight into its pathology, but their use and interpretation in clinical practice for diagnosis and prognostication remain undetermined. We sought to investigate reported correlations of serum biomarkers with presence and degree of HE in children. Methods: We conducted a systematic review of studies examining novel serum biomarkers and cytokines in association with HE that included children on PubMed, Embase, Lilacs, and Scopus. We utilized Covidence for abstract and text review by 2 independent reviewers for each study. Results: We reviewed 2824 unique publications; 15 met criteria for inclusion. Categories of biomarkers reported were inflammatory cytokines, products of amino acid metabolism, trace elements and vitamins, and hepatic and neuro biomarkers. Of 19 individual biomarkers, only 5 were measured in more than 1 study. Elevations in interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were most commonly reported as associated with HE. Notably, we observed lower average IL-6 and TNF-alpha levels in pediatric-only studies compared to mixed age studies. Overall, high bias and poor applicability to our review question was observed. We encountered low numbers of studies with pediatric focus, and few conducted with low bias study designs. Conclusion: Investigated biomarkers span a large range of categories and suggest potentially useful correlations with HE. Further well-designed prospective biomarker research is necessary to better elucidate the pathogenesis of HE in children and improve early detection and clinical care.

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The effect of GABA on serum and hepatic polyamine concentrations after partial hepatectomy in rats

et al. 1991

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Serum and hepatic polyamine concentrations in-inhibitory properties (5-7 1. Although the mechanism eluding putrescine, spermidine and spermine were whereby GABA inhibits cell growth has yet to be documented at Various time intervals after Partial determined, GABA has been reported to alter ornithine hePatectomY in rats treated with GABA (500 PdW decarboxylase (ODC) activity, the enzyme primarily body wt) Or isotonic saline. Aside from a transient responsible for polyamine synthesis (8, 9). Of interest, effect on serum polyamine concentrations. In the liver, however, GABA treatment markedly attenuated the animals and with fulminant increase in hepatic putrescine concentrations that hepatic failure, a condition in which hepatic regeneroccurs after partial hepatectomy such that levels were ative activity may be suppressed (10-13). The PuTose of 646, 74% and 1ooo/t lower than in saline-treated con-this study was to determine whether systemic serum trols on days 1, 2 and 3 after partial hepatectomy GABA concentrations similar to those reported in (p < 0.005, p < 0.01 and p < 0.05, respectively). Sper-animals and humans with liver failure interfere with midine and spermine concentrations in the liver were hepatic polymine synthesis. not affected by GABA treatment. To determine the mechanism whereby GABA lowers putrescine concen-METHODS AND MATERIALS trations in regenerating liver, ornithine decarboxylase messenger RNA and enzyme activity were documented Animals and Surgery. Adult male Sprague-Dawley rats after GABA treatment, Although ornithine decarhx-(200 to 250 g m ) were obtained from Charles River Canada ylase messenger RNA levels were ornithine (St. Constant, Quebec). The animals were housed in a decarbowlase enzyme was si@ficantly intemperature-and light-controlled room (7 AM to 7 PM). Seventy hibited 12 after hepatectomy in GABApercent partial hepatectomies were performed with the antreated rats with saline-treated controls. imals under light ether anesthesia between 9 and 12 AM as me results of this study indicate that GABA inhibits described by Higgins and Anderson (14). Sham hepatectomies hepatic putrescine synthesis at a posttranscriptional consisted of laparotomy and exteriorization of an identical level in rats after hepatectomy. amount of liver tissue for a similar time as that required for a could help to explain the impairment in hepatic regen-70% partial hepatectomy. erative activity that occurs in patients with elevated Study Croups. In GABA-treated animals, preliminary exserum GABA concentrations and fdminant hepatic periments in which serum GABA concentrations were deterfailure. (HEPATOLOGY 199 1; 14:685-689.) mined 4 h r after intraperitoneal GABA administration (peak level) and immediately before the next dose of GABA (trough level) were used to derive the dosage of GABA required to promotors Of provide serum concentrations that approximate those reported ProkWotic and eukWotic cells (1). Previous data in animals and humans with fulminant hepatic failure (5 to 30 indicate that polyamines and putr...

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Elevated Serum γ-Aminobutyric Acid Levels in Children with Reyeʼs Syndrome

Cited by 8 publications

References 0 publications

Is the hypotension of cirrhosis a GABA-mediated process?

Is the hypotension of cirrhosis a GABA-mediated process?

Novel Serum Biomarkers Associated With Pediatric Hepatic Encephalopathy: A Systematic Review

The effect of GABA on serum and hepatic polyamine concentrations after partial hepatectomy in rats

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