Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats

Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF) was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg−1·day−1) intraperitoneally for 2 weeks. The TAA-CLF rats were randomly divided into five groups (n=8) treated orally for 14 days (mg·kg−1·day−1) as follows: TAA (distilled water), losartan (5 and 10 mg/kg), and candesartan (0.1 and 0.3 mg/kg). Rats were tested for rotarod and open-field tests. Serum and hepatic biochemical markers, and hepatic histopathological changes were evaluated by H&E and Masson's staining. The TAA-CLF rats showed significant increases of hepatic malondialdehyde, hepatic expression of tumor necrosis factor-α (TNF-α), and serum ammonia, alanine aminotransferase, γ-glutamyl transferase, TNF-α, and malondialdehyde levels as well as significant decreases of hepatic and serum glutathione levels. All treatments significantly reversed these changes. The histopathological changes were moderate in losartan-5 and candesartan-0.1 groups and mild in losartan-10 and candesartan-0.3 groups. Only candesartan significantly improved TAA-induced motor dysfunction. In conclusion, therapeutic antifibrotic effects of losartan and candesartan in thioacetamide-induced hepatic fibrosis in rats are possibly through angiotensin-II receptor blocking, antioxidant, and anti-inflammatory activities. Improved motor dysfunction by candesartan could be attributed to better brain penetration and slower "off-rate" from angiotensin-II receptors. Clinical trials are recommended.

Association between MFN2 gene polymorphisms and the risk and prognosis of acute liver failure: a case-control study in a Chinese population

This study aimed to determine the role of mitofusin 2 (MFN2) gene polymorphisms in the risk and prognosis of acute liver failure (ALF). A total of 298 blood samples were collected from 138 ALF patients (case group) and 160 healthy participants (control group). Coagulation function, glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), total bilirubin (TB), blood ammonia and lactic acid (LA) were measured. The predictive evaluation of MFN2 gene polymorphisms in the risk and prognosis of ALF patients was estimated using Kaplan-Meier survival analysis, haplotype analysis, binary logistic regression analysis and Cox regression analysis. Higher levels of GPT, GOT, TB, blood ammonia and LA were observed in ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 than in those with the CC genotype of these two SNPs. The GTACAGC and GTGTGGC haplotypes were a protective factor and a risk factor for ALF, respectively. Blood ammonia and LA levels were independent risk factors and the CC genotype of rs873457 and the CC genotype of rs4846085 were protective factors for ALF. ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 had a lower survival rate than those with other genotypes of these two SNPs. The rs4846085 and rs873457 polymorphisms were both independent factors affecting the prognosis of ALF patients. MFN2 gene polymorphisms (rs873457, rs2336384, rs1474868, rs4846085 and rs2236055) may be associated with ALF and the rs873457 and rs4846085 polymorphisms are correlated with the risk and prognosis of ALF.

Initial Serum Ammonia as a Predictor of Neurologic Complications in Patients with Acute Glufosinate Poisoning

PURPOSE: Glufosinate poisoning can cause neurologic complications that may be difficult to treat due to delayed manifestation. Studies assessing possible predictors of complications are lacking. Although serum ammonia level is a potential predictor of severe neurotoxicity, it has only been assessed via case reports. Therefore, we investigated factors that predict neurologic complications in acute glufosinate-poisoned patients. MATERIALS AND METHODS: We conducted a retrospective review of 45 consecutive glufosinate-poisoning cases that were diagnosed in the emergency department (ED) of Wonju Severance Christian Hospital between May 2007 and July 2014. Patients with a Glasgow Coma Scale (GCS) score of <8, seizure, and/or amnesia were defined to a neurologic complication group. RESULTS: The neurologic complication group (29 patients, 64.4%) comprised patients with GCS<8 (27 patients, 60.0%), seizure (23 patients, 51.1%), and amnesia (5 patients, 11.1%). Non-neurologic complications included respiratory failure (14 patients, 31.1%), intubation and ventilator care (23 patients, 51.1%), shock (2 patients, 4.4%), pneumonia (16 patients, 35.6%), acute kidney injury (10 patients, 22.2%), and death (4 patients, 8.9%). Complications of GCS<8, seizure, respiratory failure, and intubation and ventilator care appeared during latent periods within 11 hrs, 34 hrs, 14 hrs, and 48 hrs, respectively. Initial serum ammonia was a predictor of neurologic complications [odds ratio 1.039, 95% confidence interval (1.001-1.078), p=0.046 and area under the curve 0.742]. CONCLUSION: Neurologic complications developed in 64.4% of patients with acute glufosinate poisoning. The most common complication was GCS<8. Initial serum ammonia level, which can be readily assessed in the ED, was a predictor of neurologic complications.

Study of plasma amino acid levels in children with autism: an Egyptian sample

The aetiology of autism is unclear and autistic symptoms had been attributed to an abnormal functional imbalance in neurotransmitter amines such as dopamine, noradrenaline and serotonin. To study plasma essential and non-essential amino acid levels, protein electrophoresis, serum ammonia, and urea in autistic children in comparison with controls. Twenty autistic children were compared to twenty healthy age and sex matched normal children serving as control, where serum amino acids, urea, ammonia and protein electrophoresis were estimated. As regards essential amino acid levels, autistic children had significant lower plasma levels of leucine, isoleucine, phenylalanine, methionine and cystine than controls [P < 0.05],while there was no statistical difference in the level of tryptophan, valine, threonine, arginine, lysine and histidine [P > 0.05]. In non-essential amino acid levels, phosphoserine was significantly raised in autistic children than in controls [.P < 0.05]. Autistic children had lower level of hydroxyproline, serine and tyrosine than controls [P < 0.05]. On the other hand there was no significant difference in levels of taurin, asparagine, alanine, citrulline, GABA, glycine, glutamic acid, and ornithine [P > 0.05]. There was no significant difference between cases and controls as regards the levels of urea, ammonia, total proteins, albumin and globulins [alpha 1, alpha 2, beta and gamma] [P > 0.05]. Autistic children had lower levels of some plasma amino acids except for glycine and glutamic acids and phosphoserine were increased with normal serum levels of urea, ammonia, total proteins, albumin and globulins [alpha 1, alpha 2, beta and gamma]

Ammonia levels and the severity of hepatic encephalopathy

To evaluate the correlation between ammonia levels with the severity of HE in patients coming to the tertiary care hospital with liver cirrhosis and hepatic encephalopathy [HE]. Descriptive, analytical study. Shifa International Hospital, Islamabad, from January 2011 to February 2012. A total of 135 patients with liver cirrhosis and HE had serum ammonia levels measured on admission. The diagnosis of HE was based on clinical criteria, and its severity was graded according to the West Haven Criteria for grading of mental status. Ammonia levels were correlated with the severity of HE using Spearman rank correlation. Out of 20 patients with normal ammonia levels, 13 [65%] were in HE I-II, 6 [30%] were in grade-III, while 1 [5%] patient was in grade-IV HE. Out of 45 patients with mild hyperammonemia, 27 [60%] were in grade I-II, 12 [26%] were in grade-III and 6 [13%] were in grade-IV HE. Out of 34 patients with moderate hyperammonemia, 9 [26%] were in grade I-II, 18 [53%] were in grade-III, and 7 [20%] were in grade-IV HE. Out of 36 patients with severe hyperammonemia, 31 [86%] patients were in grade-IV HE [p < 0.001]. Ammonia levels correlated with the severity of hepatic encephalopathy. Greater the ammonia level, severe is the grade of hepatic encephalopathy

Association of Helicobacter pylori with Elevated Blood Ammonia Levels in Cirrhotic Patients: A Meta-Analysis

PURPOSE: The association between Helicobacter pylori (H. pylori) and blood ammonia levels in cirrhotic patients is controversial. We aimed to clarify this controvercy by performing a meta-analysis of published studies. MATERIALS AND METHODS: We searched PubMed, EMBASE and Cochrane library for studies which explored the association between H. pylori and blood ammonia levels in cirrhotic patients before May 2012. Six cohort studies involved in 632 H. pylori positive and 396 H. pylori negative cirrhotic patients were eligible for our analysis. The summary estimates were presented as standard means differences (SMD) and 95% confidence intervals (CI) from individual studies. RESULTS: Overall, there was significant association between H. pylori infection and the elevated blood ammonia levels in cirrhotic patients (SMD=0.34, 95% CI=0.21-0.47, I2=42.1%). Sensitivity analysis further confirmed this association. Subgroup analysis showed that the association was found only in Asian ethnicity, but not in Caucasian ethnicity. CONCLUSION: H. pylori infection is associated with elevated blood ammonia levels in cirrhotic patients, and more large scale studies and stratify analysis are warranted in order to further evaluate this association.

Acute Hepatic Encephalopathy Presenting as Cortical Laminar Necrosis: Case Report

We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.

Hyperammonemia in a Patient with Late-Onset Ornithine Carbamoyltransferase Deficiency

Ornithine carbamoyltransferase (OTC) deficiency is a urea cycle disorder that causes the accumulation of ammonia, which can lead to encephalopathy. Adults presenting with hyperammonemia who are subsequently diagnosed with urea cycle disorders are rare. Herein, we report a case of a late-onset OTC deficient patient who was successfully treated with arginine, benzoate and hemodialysis. A 59-yr-old man was admitted to our hospital with progressive lethargy and confusion. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. A plasma amino acid and urine organic acid analysis revealed OTC deficiency. Despite the administration of a lactulose enema, the patient's serum ammonia level increased and he remained confused, leading us to initiate acute hemodialysis. After treatment with arginine, sodium benzoate and hemodialysis, the patient's serum ammonia level stabilized and his mental status returned to normal.

Plasma levels of tumor necrosis factor-alpha and ammonia in patients with liver cirrhosis: correlation with severity of hepatic encephalopathy

The pathogenesis of hepatic encephalopathy [HE] is still incompletely understood, and the precise mechanisms causing brain dysfunction in liver failure are still not fully established. Several theories concerning the pathogenesis of HE have been previously suggested, including the ammonia theory, which received the most attention. Ammonia is still the most incriminated substance in the pathogenesis of HE. However, several problems exist with the ammonia theory. It is traditionally considered that circulating ammonia levels do not correlate well with severity of HE, and some patients with HE have normal circulating levels of ammonia. Another theory is that TNF-alpha is implicated in apoptosis of hepatocytes. This study aimed to determine the plasma levels of TNF-alpha and ammonia in patients with liver cirrhosis and their relation to hepatic encephalopathy [HE]. Circulating levels of TNF-alpha and ammonia were measured in 84 patients with liver cirrhosis [due to hepatitis C in 50 patients and due to hepatitis B in 34 patients], 21 of them had no HE and 63 had various clinical grades of HE [grades 1-4]. TNF-alpha concentrations were measured using commercially available solid-phase high sensitivity enzyme-linked immunosorbent assay. Ammonia levels were determined in venous plasma by the Berthelot reaction. Twenty four healthy controls with matched age and sex were included in the study. There were a statistically significant difference between plasma levels of TNF-alpha and ammonia in patients with liver cirrhosis compared to healthy controls. A significant positive correlation was found between circulating levels of TNF-alpha and those of ammonia [r=0.974, P< 0.0001], and also between circulating levels of both substances and severity of HE in all studied patients [r=0.950, P<0.0001, and r=0.900, P<0.0001 respectively]. TNF-alpha and ammonia were both significant independent predictors of severity of HE [P<0.0001 for both variables]. The results of this study demonstrate a significant positive relationship between TNF-alpha and ammonia in patients with chronic liver disease with HE and strengthen the suggestion that TNF-alpha could be strongly involved in the pathogenesis of HE which would stimulate the development of new treatment modalities to decrease this cytokine. This possibility needs further investigation and elucidation

A new experimental model for acute hepatic failure in rats / Novo modelo experimental em ratos para insuficiência hepática aguda

PURPOSE: To develop a reliable surgical model of acute hepatic failure and hyperammonemia in rats that avoids porto-systemic shunt and bile duct ligation, applicable to hepatic encephalopathy research. METHODS: The pedicles of right lateral and caudate lobes were exposed and clamped. One hour later, the animal was reopened, clamps were released and anterior subtotal hepatectomy (resection of median and left lateral lobes) was performed, comprising 75 percent of liver removal. Four hours after hepatectomy, blood samples and liver tissues were collected from ALF and control groups. RESULTS: Differences between ALF and control groups were significant for ALT, AST, total and direct bilirubin, sodium, potassium, alkaline phosphatasis, gamma-glutamyltransferase and most important, ammonia. Histologically, significant differences were noticed between groups. CONCLUSION: The model is useful for the study of specific aspects of ALF and the development of new therapeutic approaches.

OBJETIVO: Desenvolver um modelo cirúrgico de IHA e hiperamonemia em ratos, que evita o shunt porto-sistêmico e a ligadura do ducto biliar, que seja aplicável à pesquisa de encefalopatia hepática. MÉTODOS: Após anestesia geral e laparotomia mediana, os pedículos dos lobos laterais direito e caudado foram isolados e clampeados. Após 1 hora, o animal foi reaberto, os clampes retirados e foi realizada hepatectomia anterior subtotal (ressecção dos lobos médio e lateral esquerdo), compreendendo a remoção de 75 por cento do parênquima. Quatro horas após a hepatectomia, amostras de sangue e tecido hepático foram coletadas nos grupos IHA e controle. RESULTADOS: Diferenças entre os grupos IHA e controle foram significativas para ALT, AST, bilirrubina total e direta, sódio, potássio, fosfatase alcalina, gama glutamiltransferase e principalmente amônia. Histologicamente, diferenças significativas foram observadas entre os grupos. CONCLUSÃO: O modelo é útil para o estudo de aspectos específicos da IHA e o desenvolvimento de novas abordagens terapêuticas.

Métodos de avaliação da fadigabilidade muscular periférica e seus determinantes energético-metabólicos na DPOC / Methods for the assessment of peripheral muscle fatigue and its energy and metabolic determinants in COPD

Está bem estabelecido que, além do acometimento pulmonar, a DPOC apresenta consequências sistêmicas que podem convergir para a disfunção muscular periférica, com maior fadigabilidade muscular, menor tolerância ao exercício e menor sobrevida nesses pacientes. Tendo em vista as repercussões negativas da fadiga muscular precoce na DPOC, esta revisão teve como objetivo discutir os principais achados da literatura relacionados aos seus determinantes metabólicos e bioenergéticos e suas repercussões funcionais, bem como seus métodos de identificação e de quantificação. O substrato anatomofuncional da maior fadigabilidade muscular na DPOC parece incluir a redução dos níveis de fosfatos de alta energia, a redução da densidade mitocondrial, a lactacidemia precoce, o aumento da amônia sérica e a perfusão muscular reduzida. Essas alterações podem ser evidenciadas por falência de contração, redução da taxa de disparo das unidades motoras e maior recrutamento de unidades motoras numa dada atividade, exteriorizando-se funcionalmente por redução da força, potência e resistência musculares. Esta revisão mostra também que diversos tipos de regimes contráteis e protocolos têm sido utilizados com o intuito de detectar fadiga nessa população. A partir de tais conhecimentos, estratégias reabilitadoras podem ser traçadas visando o aumento da resistência à fadiga muscular nessa população.

It has been well established that, in addition to the pulmonary involvement, COPD has systemic consequences that can lead to peripheral muscle dysfunction, with greater muscle fatigue, lower exercise tolerance and lower survival in these patients. In view of the negative repercussions of early muscle fatigue in COPD, the objective of this review was to discuss the principal findings in the literature on the metabolic and bioenergy determinants of muscle fatigue, its functional repercussions, as well as the methods for its identification and quantification. The anatomical and functional substrate of higher muscle fatigue in COPD appears to include lower levels of high-energy phosphates, lower mitochondrial density, early lactacidemia, higher serum ammonia and reduced muscle perfusion. These alterations can be revealed by contraction failure, decreased firing rates of motor units and increased recruitment of motor units in a given activity, which can be functionally detected by a reduction in muscle strength, power and endurance. This review article also shows that various types of muscle contraction regimens and protocols have been used in order to detect muscle fatigue in this population. With this understanding, rehabilitation strategies can be developed in order to improve the resistance to muscle fatigue in this population.

A critical analysis of studies assessing L-ornithine-L-aspartate (LOLA) in hepatic encephalopathy treatment / Uma análise crítica dos estudos de avaliação do L-ornitina-L-aspartato (LOLA) no tratamento da encefalopatia hepática

CONTEXT: Experimental and clinical studies suggest that LOLA may have a favorable influence on hepatic encephalopathy due to the effect on the reduction of ammonia, and improvement of the symptoms and laboratory findings. OBJECTIVES: To evaluate and to critically analyze the efficacy and/or effectiveness results of the use of LOLA when compared to placebo in the treatment of hepatic encephalopathy. DATA SOURCES: LILACS, SciELO, MEDLINE, PubMed database and Cochrane Collaboration Register of Controlled Trials were searched from 1966 to September of 2006. The review has included all the randomized controlled double-blind clinical trials performed in humans in English language. RESULTS: Four studies published between 1993 and 2000 were selected and reviewed. LOLA was showed as being able to reduce hyperammonemia in patients with hepatic encephalopathy, when compared to patients in the placebo group. CONCLUSIONS: Although the trials have shown efficacy of LOLA in reducing hyperammonemia of hepatic encephalopathy, sufficient evidence of a significant beneficial effect of LOLA on patients with hepatic encephalopathy was not found. The studies performed in this area were small, with short follow-up periods and half of them showed low methodological quality.

CONTEXTO: Estudos experimentais e clínicos sugerem que a L-ornitina-L-aspartato pode ter uma influência favorável na encefalopatia hepática em virtude do seu efeito na redução da amônia, e melhora dos sintomas e achados laboratoriais. OBJETIVOS: Avaliar e analisar criticamente os estudos de eficácia e/ou efetividade do uso de L-ornitina-L-aspartato quando comparado com placebo no tratamento da encefalopatia hepática. FONTES DE INFORMAÇÃO: Foram pesquisadas as bases de dados LILACS, SciELO, MEDLINE, PubMed e o Registro de Ensaios Controlados da Colaboração Cochrane no período de 1966 até setembro de 2006. A revisão incluiu todos os ensaios clínicos controlados randomizados, duplo-cego, em seres humanos, no idioma inglês. RESULTADOS: Foram selecionados e revisados quatro estudos publicados entre 1993 e 2000, que mostraram que a L-ornitina-L-aspartato foi capaz de reduzir a hiperamonemia em portadores de encefalopatia hepática, quando comparados ao grupo que utilizou placebo. CONCLUSÕES: Embora os estudos tenham demonstrado eficácia da L-ornitina-L-aspartato em reduzir a hiperamonemia da encefalopatia hepática, não foi encontrada evidência suficiente que a L-ornitina-L-aspartato tenha um efeito clínico benéfico significativo em pacientes com encefalopatia hepática. Os ensaios realizados neste campo foram pequenos com períodos curtos de acompanhamento e a metade deles com baixa qualidade metodológica.

Detecção de encefalopatia hepática mínima através de testes neuropsicológicos e neurofisiológicos e o papel da amônia no seu diagnóstico / Minimal hepatic encephalopathy detection by neuropsychological and neurophysiological methods and the role of ammonia for its diagnosis

CONTEXTO: A encefalopatia hepática mínima vem sendo sistematicamente investigada em pacientes com cirrose hepática. Entretanto, existem controvérsias quanto aos melhores métodos, bem como o papel da amônia para seu diagnóstico. OBJETIVO: Avaliar a frequência de encefalopatia hepática mínima diagnosticada através de testes neuropsicológicos e neurofisiológicos em cirróticos, bem como os possíveis fatores de risco para esta condição, incluindo o papel da concentração arterial de amônia em seu diagnóstico. MÉTODOS: Indivíduos com cirrose hepática foram avaliados através do teste de conexão numérica partes A e B (TCN-A e TCN-B) e potencial evocado relacionado a eventos (P300). O diagnóstico de encefalopatia hepática mínima foi feito quando da presença de anormalidade no P300 e em, pelo menos, um dos testes neuropsicológicos. As concentrações arteriais de amônia, a escolaridade e a gravidade da cirrose hepática também foram avaliadas em todos. RESULTADOS: Foram avaliados 48 pacientes cirróticos, com média de idade 50 ± 8 anos, sendo 79 por cento do sexo masculino. As principais causas foram a alcoólica e a viral. O P300 foi anormal em 75 por cento dos casos e o TCN-A e TCN-B anormais em 58 por cento e 65 por cento dos casos, respectivamente. Os resultados do TCN-B foram influenciados pela escolaridade. A frequência de encefalopatia hepática mínima foi de 50 por cento. A concentração arterial de amônia não foi significantemente maior em pacientes com diagnóstico de encefalopatia hepática mínima (195 ± 152 mmol/L versus 148 ± 146 mmol/L; P>0,05). Não houve diferença significante entre os grupos com e sem encefalopatia hepática mínima quanto às demais variáveis estudadas. CONCLUSÃO:A encefalopatia hepática mínima é condição frequente em pacientes com cirrose hepática. A concentração arterial de amônia não parece ter papel importante no seu diagnóstico.

CONTEXT: Minimal hepatic encephalopathy has been systematically investigated in cirrhotic patients. Although, there are controversies regarding the best methods as well as the role of ammonia for its diagnosis. OBJECTIVE: To evaluate the frequency of minimal hepatic encephalopathy diagnosed by neuropsychological and neurophysiological methods in cirrhotic patients, as well as possible associated risk factors for this condition, including the role of arterial ammonia concentrations for its diagnosis. METHODS: Cirrhotic patients were evaluated by the number connection test parts A and B (NCT-A and NCT-B), and auditory evoked-related potentials (P300). Minimal hepatic encephalopathy was diagnosed by the presence of abnormal P300 and in unless one of the performed neuropsychologic tests. Arterial ammonia concentration, scholarity and cirrhosis severity accessed by Child-Pugh classification were evaluated in all. RESULTS: Forty-eight cirrhotic patients were evaluated, with median age 50 ± 8 years old, 79 percent male. The main etiologies were alcoholic and viral. The P300 was abnormal in 75 percent of cases, while NCT-A and NCT-B were abnormal in 58 percent and 65 percent, respectively. The NCT-B results were influenced by scholarity. The minimal hepatic encephalopathy frequency was 50 percent. Arterial ammonia concentration was not significantly increased in minimal hepatic encephalopathy diagnosed patients (195 ± 152 mmol/L versus 148 ± 146 mmol/L; P>0,05). There was no difference between groups with or without minimal hepatic encephalopathy in the other studied variables. CONCLUSION: Minimal hepatic encephalopathy is a frequent condition in cirrhotic patients. The arterial ammonia concentration does not play a major role in its diagnosis.

Effect of barn ventilation on blood gas status and some physiological traits of dairy cows.

Twenty Holstein friesian and Brown swiss cows were used to investigate the effect of insufficient in barn ventilation on blood gas status and some physiological traits of the cows. Animals were kept in mechanically ventilated barn in stall barn (I); and the ventilation funnels of the barn were closed to simulate traditional habits of the region's breeders (II); then cows were transfered open-shed barn (III). For each experimental of 10 days period, respiration and pulse rates and blood gas of animals were measured. Temperature, relative humidity, CO2 and NH3 concentrations were recorded in each barns. In mechanically ventilated barn, climatic and atmospheric gas was in normal ranges for the cows but in unventilated barn they were at the upper levels. In experiment II, blood pH was decreased without pCO2 change. The highest blood pO2 and HCO3(-) levels were found when the animals were kept in open-shed barn (III). Measured parameters were not influenced by breed of the cows. Blood pH, pO2 HCO3(-), respiration and pulse rates of the cows were significantly affected by barn types (p < 0.05 and p < 0.01). Respiration and pulse rates were higher in inadequate (II) barn conditions than those of open-shed. Higher levels of gases, especially carbon dioxide, in the unventilated barn significantly influenced biological parameters of cows. It is concluded that poor ventilation caused considerable changes in physiologic parameters of the cows and can potentially affect animal health and production.

Minimal hepatic encephalopathy: time to recognise and treat.

Minimal hepatic encephalopathy represents a part of the spectrum of hepatic encephalopathy and is the mildest form. While patients with hepatic encephalopathy have impaired intellectual functioning, personality changes, altered levels of consciousness, and neuromuscular dysfunction, patients with minimal hepatic encephalopathy have no recognisable clinical symptoms of hepatic encephalopathy but have mild cognitive and psychomotor deficits. The prevalence of minimal hepatic encephalopathy has been reported to vary between 30% and 84% in patients with liver cirrhosis and is higher in patients with poor liver function. The diagnosis is usually made by neuropsychological and/or neurophysiological testing in cirrhotic patients who are otherwise normal on neurological examination. Minimal hepatic encephalopathy is a clinically significant disorder that impairs the health-related quality of life, predicts the development of overt encephalopathy and is probably associated with a poor prognosis. Thus screening all patients with cirrhosis for minimal hepatic encephalopathy using psychometric testing is recommended. Pharmacologic therapy is recommended for patients diagnosed with minimal hepatic encephalopathy. The pathogenesis of minimal hepatic encephalopathy is considered similar to that of overt hepatic encephalopathy and ammonia plays a key role. Thus ammonia lowering agents such as lactulose, L-ornithine and L-aspartate that have good safety profiles are recommended. Future studies will better define the role of probiotics, levocarnitine and sodium benzoate.

L-ornithine-L-aspartate infusion efficacy in hepatic encephalopathy

To determine the efficacy of L-ornithine-L-aspartate in treatment of hepatic encephalopathy. Randomized, placebo-controlled trial. Department of Gastroenterology and Hepatology, Sheikh Zayed Hospital, Lahore, from February to August 2005. Cirrhotic patients with hyperammonemia and overt hepatic encephalopathy were enrolled. Eighty patients were randomized to two treatment groups, L-ornithine-L-aspartate [20g/d] or placebo, both dissolved in 250mL of 5% dextrose water and infused intravenously for four hours a day for five consecutive days with 0.5 g/kg dietary protein intake at the end of daily treatment period. Outcome variables were postprandial blood ammonia and mental state grade. Adverse reactions and mortality were also determined. Both treatment groups were comparable regarding age, gender, etiology of cirrhosis, Child-Pugh class, mental state grade and blood ammonia at baseline. Although, improvement occurred in both groups, there was a greater improvement in L-ornithine-L-aspartate group with regard to both variables. Four patients in the placebo group and 2 in L-ornithine-L-aspartate group died. L-ornithine-L-aspartate infusions were found to be effective in cirrhotic patients with hepatic encephalopathy

Effect of triple therapy for helicobacter pylori eradication on hepatic encephalopathy: a randomized controlled trial

Helicobacter pylori [H. pylori] infection could potentially contribute to the development and severity of hepatic encephalopathy due to strong urease activity in the stomach of H. pylori infected cirrhotic patients. To assess the effect of triple eradication therapy for H. pylori on hepatic encephalopathy. Open randomized controlled clinical trial with 4 arms. liver diseases unit in Suez Canal University Hospital - tertiary care. Forty four Hp+ [Group 1] and 44 Hp- patients [Group 2] [based on rapid urease test of gastric biopsy] with hepatic encephalopathy grade 1 - 3. Triple eradication therapy for H. pylori versus standard treatment for hepatic encephalopathy in group 1 and antimicrobial therapy [without Omeprazole] versus standard treatment in group 2 for 14 days. Blind assessment of the grade of encephalopathy before and within three days from end of treatment. One grade improvement was considered treatment success. Success rate was 18.2% in standard treatment and 63.6% in triple therapy [p< 0.001] in H pylori positive. While in H. pylori negative patients the success was 9.1% in standard treatment versus 59.1% [P< 0.001] in and antimicrobial therapy. Success rate was not significantly different between standard treatment or between triple therapy and antimicrobial therapy among both groups. Among other factors in logistic regression models both triple therapy [OR: 1.03<6.22<37.69, P= 0.047] and antimicrobial therapy [OR: 2.09<11.42<59.46, P= 0.02] were significant predictors of success in the respective groups. Both triple eradication therapy for H. pylori and antimicrobial therapy only, equally improve the outcome of management of hepatic encephalopathy. The improvement may be attributed to the effect of antimicrobial therapy on ammonia producing gut flora rather than H. pylori eradication. H pylori eradication therapy adds no benefit in hepatic encephalopathy

Early graft function and carboxyhemoglobin level in liver transplanted patients

Heme-Oxygenase-1 catalyzes hemoglobin into bilirubin, iron, and carbon monoxide, a well known vasodilator. Heme-Oxygenase-1 expression and carbon monoxide production as measured by blood carboxyhemoglobin levels, increase in end stage liver disease patients. We hypothesized that there may be a correlation between carboxyhemoglobin level and early graft function in patients undergoing liver transplant surgeries. In a descriptive retrospective study, 39 patients who underwent liver transplantation between the year 2005 and 2006 at KFSH and RC, are included in the study. All patients received general anesthesia with isoflurane in 50% oxygen and air. Levels of oxyhemoglobin, carboxyhemoglobin and methemoglobin concentration in percentage were recorded at preoperative time, anhepatic phase, end of surgery, ICU admission and 24 hr after surgery. The level of lactic acid, prothrombin time [PT], partial thrombin time [PTT], serum total bilirubin and ammonia were also recorded at ICU admission and 24 hr after surgery. The numbers of blood units transfused were recorded. 39 patients were included in the study with 13/39 for living donor liver transplant [LDLT] compared to 26/39 patients scheduled for deceased donor liver transplant [DDLT]. The mean age was 35.9 +/- 16.9 years while the mean body weight was 60.3 +/- 20.9 Kg. Female to male ratio was 21/18. The median packed red blood cell [PRBC] units was 4 [Range 0-40]. There was a significant increase in carboxyhemoglobin level during the anhepatic phase, end of surgery and on ICU admission compared with preoperative value [p < 0.005]. However, there was insignificant changes in methemoglobin level and significant decrease in oxyhemoglobin levels throughout the study period compared to the preoperative value [p < 0.005]. The changes in carboxyhemoglobin level on ICU admission and 24 hrs postoperatively were positively correlated with the changes in serum total bilirubin and prothrombin time [R = 0.35, 0.382, 0.325 and 0.31] respectively p < 0.05] but not with the changes in serum lactic acid. The same strong correlation was found when analysing LDLT and DDLT patients separately between carboxyhemoglobin concentration and PT and total bilirubin while still the correlation with lactic acid was weak. There was no correlation between average perioperative carboxyhemoglobin concentration during different timing of measurements and average units of transfused blood [R = -0.02] p > 0.05. The changes in carboxyhemoglobin level significantly correlate with the changes in graft functions particularly prothrombin time and serum total bilirubin and may be used as an early, rapid and simple test for early evaluation of graft function

Serum levels of astroglial S100-beta and neuron-specific enolase in hepatic encephalopathy patients

To find a reliable, noninvasive method for the diagnosis of cognitive impairment in patients with hepatic cirrhosis we measured serum levels of astroglial S100beta and neuron-specific enolase in cirrhotic patients with and without hepatic encephalopathy [HE]. S100beta levels showed a significant increase in groups with HE stage 1 and 2 compared to both control and cirrhosis patients. However serum neuron-specific enolase levels were not significantly different between the studied groups. S100beta levels had a specificity of 91.3% and sensitivity of 51.7% for detection of HE from cirrhosis. Serum S100beta may be a useful surrogate marker for the diagnosis of mild cognitive impairment in cirrhotic patients before they progress to more advanced stages of HE

Study of neurometabolic disorders in Egyptian children

Background: Metabolic brain diseases usually present with a complex neurological picture so they are often overlooked. This prospective study was undertaken to focus on the clinical aspects, biochemical abnormalities and neuroimaging of the brain in children suffering from neurometabolic disorders

Patients and methods: This study was carried out on 130 patients suspected clinically of having metabolic brain diseases and presented to the neuropediatric clinic, neonatal intensive care unit in Benha faculty of medicine and the neurometabolic specialized clinic in Abu El-Reesh hospital. The diagnosis of neurometabolic disorders was confirmed in 29 children [22%]. They were 19 males and 10 females, their age ranged from 5 days to 10 yrs with mean age 3.61 +/- 2.2 years. They presented with clinical manifestations suggestive of metabolic brain diseases. They were subjected to thorough history, clinical examination, investigations in the form of serum ammonia, serum lactate ,blood glucose, blood gases assessment, ketone bodies in urine, CPK [creatine phosphokinase],urine organic acids, plasma aminogram, enzymatic assay, EMG [Electromyography],EEG[electroencephalography], muscle biopsy, CT and MRI of the brain

Results: Patients were classified according to their clinical presentations, biochemical and radiological findings into 5 groups, Group I, Organic acidemia 10 cases [34.5%], including, Methyl malonic acidemia [4 cases], Biotinidase deficiency [3 cases], Glutaric Aciduria type 1 [2 cases] and Maple syrup urine disease [one case]. Group II, Mitochondrial disorders 9 cases [31%] including, Leigh syndrome [4 cases], Pyruvate dehydrogenase deficiency [2 cases], mitochondrial encephalomyopathy [2 cases] and MELAS syndrome[mitochondrial encephalopathy, lactic acidosis and stroke] [one case]. Group III, Urea cycle abnormalities 5 cases [17.2 %]. Group IV Aminoacidopathy 3 cases [10.4 %]in the form of Phenylketonuria. Group V Fatty acid oxidation defect 2 cases [6.9%]. The main neurological manifestations were global developmental delay [93.1%], seizures [89.7%], hypertonia [65.5%] and microcephaly [55.2%]. Biochemical abnormalities were: Group I: had acidosis in 9 cases[90%] [ketoacidosis in [4 cases],lactic acidosis in[3 cases],acidosis without ketosis in [2 cases]], ketosis only in one case [10%] and hyperammonemia in 7 cases [70%] of cases. GroupII: had mainly lactic acidosis 5 cases [55.6%] and mild hyperammonemia [11.1%]. GroupIII: had isolated hyperammonemia [100%]. Group IV: had hyperphenylalaninemia in [100%] of cases with phenylketonuria. Group V: had lactic acidosis,mild hyperammonemia, hypoglycemia and absent ketosis in [100%]of cases. Neuroimaging showed abnormal findings in the form of basal ganglia abnormalities [41.4%], brain atrophy [27.5%], diffuse demeylination and focal demeylination [6.9%]each and normal findings in [17.3%]

Conclusion: Presence of unexplained neurological symptoms whose severity is out of proportion to the inciting illness should arouse suspicion of a metabolic disease. Screening tests like blood gas analysis, blood levels of lactate, glucose and ammonia, urine examination for ketones and neuroimaging provide valuable clues to the presence of an underlying metabolic disease