Search results for: minimal hepatic encephalopathy

Authors: Erwin Geroleo, Higinio Mappala

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Introduction Overt Hepatic Encephalopathy (OHE) is the most dreaded outcome of liver cirrhosis. Aside from the triggering factors which are already known to precipitate OHE, there is growing evidence that an altered gut microbiota profile (dysbiosis) can also trigger OHE. MHE is the mildest form of hepatic encephalopathy(HE), affecting about one-third of patients with cirrhosis, and close 80% of patients with cirrhosis and manifests as abnormalities in central nervous system function. Since these symptoms are subclinical most patients are not being treated to prevent OHE. The gut microbiota have been evaluated by several studies as a therapeutic option for MHE, especially in decreasing the levels of ammonia, thus preventing progression to OHE Objectives This study aims to evaluate the efficacy of probiotics in terms of reduction of ammonia levels in patient with minimal hepatic encephalopathies and to determine if Probiotics has role in the prevention of progression to overt hepatic encephalopathy in adult patients with minimal hepatic encephalopathy (MHE) Methods and Analysis The literature search strategy was restricted to human studies in adults subjects from 2004 to 2022. The Jadad Score Calculation was utilized in the assessment of the final studies included in this study. Eight (8) studies were included. Cochrane’s Revman Web, the Fixed Effects model and the Ztest were all used in the overall analysis of the outcomes. A p value of less than 0.0005 was statistically significant. Results. These results show that Probiotics significantly lowers the level of Ammonia in Cirrhotic patients with OHE. It also shows that the use of Probiotics significantly prevents the progression of MHE to OHE. The overall risk of bias graph indicates low risk of publication bias among the studies included in the meta-analysis. Main findings This research found that plasma ammonia concentration was lower among participants treated with probiotics (p<0.00001).) Ammonia level of the probiotics group is lower by 13.96 μmol/ on the average. Overall risk of developing overt hepatic encephalopathy in the probiotics group is shown to be decreased by 15% as compared to the placebo group Conclusion The analysis showed that compared with placebo, probiotics can decrease serum ammonia, may improve MHE and may prevent OHE.

Keywords: minimal hepatic encephalopathy, probiotics, liver cirrhosis, overt hepatic encephalopathy

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Authors: S. A. El-Marasy, S. A. El Awdan, R. M. Abd-Elsalam

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This study aimed to investigate the possible neuroprotective effect of chrysin on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also, the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. Male Wistar rats were randomly allocated into five groups. The first group received the vehicle (distilled water) for 21 days and is considered as normal group. While the second one received intraperitoneal dose of TAA (200 mg/kg) at three alternative days during the third week of the experiment to induce HE and is considered as control group. The other three groups were orally administered chrysin for 21 days (25, 50, 100 mg/kg) and starting from day 17; rats received intraperitoneal dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Chrysin reversed TAA-induced motor coordination in rotarod test, cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonemia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.

Keywords: chrysin, hepatic encephalopathy, oxidative stress, rats, thioacetamide, TLR4/NF-κB pathway

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Authors: Marawan Abd Elbaset Mohamed, Hanan A. Ogaly, Rehab F. Abdel-Rahman, Ahmed-Farid O.A., Marwa S. Khattab, Reham M. Abd-Elsalam

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Liver fibrosis is a severe worldwide health concern due to various chronic liver disorders. Hepatic encephalopathy (HE) is one of its most common complications affecting liver and brain cognitive function. Beta-Carotene (B-Car) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. The study attempted to know B-Car neuroprotective potential against thioacetamide (TAA)-induced neurotoxicity and cognitive decline in HE in rats. Hepatic encephalopathy was induced by TAA (100 mg/kg, i.p.) three times per week for two weeks. B-Car was given orally (10 or 20 mg/kg) daily for two weeks after TAA injections. Organ body weight ratio, Serum transaminase activities, liver’s antioxidant parameters, ammonia, and liver histopathology were assessed. Also, the brain’s mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), antioxidant parameters, adenosine triphosphate (ATP), adenosine monophosphate (AMP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) cAMP response element-binding protein (CREB) expression and B-cell lymphoma 2 (Bcl-2) expression were measured. The brain’s cognitive functions (Spontaneous locomotor activity, Rotarod performance test, Object recognition test) were assessed. B-Car prevented alteration of the brain’s cognitive function in a dose-dependent manner. The histopathological outcomes supported these biochemical evidences. Based on these results, it could be established that B-Car could be assigned to treat the brain’s neurotoxicity consequences of HE via downregualtion of MAPK/NF-κB signaling pathways.

Keywords: beta-carotene, liver injury, MAPK, NF-κB, rat, thioacetamide

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Authors: Samir Malhotra, Rajan K. Khandotra, Rakesh K. Dhiman, Neelam Chadha

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There is paucity of data about safety and efficacy of probiotic treatment on patient outcomes in cirrhosis. Specifically, it is important to know whether probiotics can improve mortality, hepatic encephalopathy (HE), number of hospitalizations, ammonia levels, quality of life, and adverse events. Probiotics may improve outcomes in patients with acute or chronic HE. However, it is also important to know whether probiotics can prevent development of HE, even in situations where patients do not have acute HE at the time of administration. It is also important to know if probiotics are useful as primary prophylaxis of HE. We aimed to conduct an updated systematic review and meta-analysis to evaluate the safety and efficacy of probiotics in patients with cirrhosis. We searched PubMed, Cochrane library, Embase, Scopus, SCI, Google Scholar, conference proceedings, and references of included studies till June 2017 to identify randomised clinical trials comparing probiotics with other treatments in cirrhotics. Data was analyzed using MedCalc. Probiotics had no effect on mortality but significantly reduced HE (14 trials, 1073 patients, OR 0.371; 95% CI 0.282 to 0.489). There was not enough data to conduct a meta-analysis on outcomes like hospitalizations and quality of life. The effect on plasma ammonia levels was not significant (SMD -0.429; 95%CI -1.034 – 0.177). There was no difference in adverse events. To conclude, although the included studies had a high risk of bias, the available evidence does suggest a beneficial effect on HE. Larger studies with longer periods of follow-up are needed to determine if probiotics can reduce all-cause mortality.

Keywords: cirrhosis, hepatic encephalopathy, meta-analysis, probiotic

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Authors: Shahla Afshar Paiman, Sedigheh Madani, Zahra Hosseininezhad

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Introduction: The most common causes of appendix luminal obstruction are fecaliths and lymphoid follicle hyperplasia. Appendicitis is a very rare Gastrointestinal complication of varicella zosterand it is mostly observed in immune-compromised patient. Case presentation: Here we reported a case of varicella zoster-related perforated appendicitis with synchronous encephalopathy as a first presentation of chickenpox in a 10-year-old boy. He had no history of immunodeficiency or predisposing factors and his diagnosis is confirmed by both serological lab tests and abdominal fluid (peritoneal secretion) PCR. Conclusion: Varicella zoster could cause appendicitis as first presentation, along with other critical complications look likes encephalopathy.

Keywords: Varicella zoster, appendicitis, encephalitis, children

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Authors: Ahmed Abdel Sattar Khalil, Hazem Omar

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Background: Image-guided hepatic interventions are integral to the management of infective and neoplastic liver lesions. Over the past decades, 2D ultrasound was used for guidance of hepatic interventions; with the recent advances in ultrasound technology, 3D ultrasound was used to guide hepatic interventions. The aim of this study was to illustrate the added value of 3D image guided hepatic interventions by x matrix technology. Patients and Methods: This prospective study was performed on 100 patients who were divided into two groups; group A included 50 patients who were managed by 2D ultrasonography probe guidance, and group B included 50 patients who were managed by 3D X matrix ultrasonography probe guidance. Thermal ablation was done for 70 patients, 40 RFA (20 by the 2D probe and 20 by the 3D x matrix probe), and 30 MWA (15 by the 2D probe and 15 by the 3D x matrix probe). Chemical ablation (PEI) was done on 20 patients (10 by the 2D probe and 10 by the 3D x matrix probe). Drainage of hepatic collections and biopsy from undiagnosed hepatic focal lesions was done on 10 patients (5 by the 2D probe and 5 by the 3D x matrix probe). Results: The efficacy of ultrasonography-guided hepatic interventions by 3D x matrix probe was higher than the 2D probe but not significantly higher, with a p-value of 0.705, 0.5428 for RFA, MWA respectively, 0.5312 for PEI, 0.2918 for drainage of hepatic collections and biopsy. The complications related to the use of the 3D X matrix probe were significantly lower than the 2D probe, with a p-value of 0.003. The timing of the procedure was shorter by the usage of 3D x matrix probe in comparison to the 2D probe with a p-value of 0.08,0.34 for RFA and PEI and significantly shorter for MWA, and drainage of hepatic collection, biopsy with a P-value of 0.02,0.001 respectively. Conclusions: 3D ultrasonography-guided hepatic interventions by  x matrix probe have better efficacy, less complication, and shorter time of procedure than the 2D ultrasonography-guided hepatic interventions.

Keywords: 3D, X matrix, 2D, ultrasonography, MWA, RFA, PEI, drainage of hepatic collections, biopsy

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Authors: Omar Sorour, Michael Leahy, Thomas Irvine, Vladimir Koren

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Introduction: Covid encephalitis is a rare yet dangerous complication, particularly affecting the older and immunocompromised. Symptoms range from confusion to delirium, coma, and seizures. Although neurological manifestations have become more well-characterized in COVID patients, little is known about whether priorneurological abnormalities may predispose patients to COVID encephalopathy. Case Description: A 73 y.o. male with a CT and MRI-confirmed stable, prior 9 mm cavernoma in the right frontal lobe and no past history of seizures was hospitalized with generalized weakness, abdominal pain, nausea, and shortness of breath with subsequent COVID pneumonia. Three days after the initial presentation, the patient developed a spontaneous generalized tonic-clonic seizure consistent with presumed COVID encephalitis, along with somnolence and confusion. A day later, the patient had two other seizure episodes. Follow-up EEG suggested an inter-ictal epileptic focus with sharp waves corresponding to roughly the same location as the patient’s pre-existing cavernoma. The patient’s seizures stopped shortly thereafter, while his encephalopathy continued for days. Conclusion: We illustrate that a pre-existing anatomic cortical abnormality may act as a potential nidus for new-onset seizure activity in the context of suggested COVID encephalopathy. Future studies may further demonstrate that manifestations of COVIDencephalopathy in certain patients may be more predictable than initially assumed.

Keywords: cavernoma, covid, encephalopathy, seizures

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Authors: Elsayed Fath Khalifa, Samer Mohamed Daghash

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The aim of the current work study to increase the anatomical knowledge about the cattle egret which considered economically important for farmers. The study was carried out on ten adult, apparently healthy cattle egrets of both sexes. Each bird was exsanguinated; the caudal vena cava was cannulated and flushed with warm normal saline solution (0.9%) then injected with blue colored neoprine (60%) latex in order to study the tributaries of the hepatic portal vein. The origin, course and tributaries of the right and left hepatic portal veins were studied. The hepatic portal venous system collected venous blood from the abdominal viscera including; glandular and muscular stomachs, liver, pancreas, spleen, small intestine and large intestine. The hepatic portal vein was formed by the left and the right hepatic portal veins. The smaller left one drained blood from the glandular and muscular stomachs through the ventral and the left proventriculus as well as the left gastric veins. The most tributaries of the right hepatic portal vein drained blood from the rest of the gastrointestinal tract and the spleen by the proventriculosplenic, the gastropancreaticoduodenal and the common mesenteric veins.

Keywords: cattle egret, common mesenteric vein, hepatic portal vein, anatomy

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Authors: Keivan Jamshidi, Afshin Zahedi

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An abattoir based study was carried out during spring 2011 to investigate pathological conditions of the liver in camels (Camelus deromedarius) slaughtered in the Semnan slaughter house, Northern East of Iran. In this study, 40 carcasses out of 150 randomly selected carcasses inspected at postmortem, found with liver lesions. Proper tissue samples obtained from the livers with macroscopic lesions, fixed in 10% neutral buffer formaldehyde, processed for routine histopathological techniques, and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by H&E staining techniques. In histopathological examination of hepatic tissues, following changes were observed: Hydatid cysts; 65%, Cirrhosis; 10%, Hepatic lipidosis (Mild to Severe fatty changes); 12.5%, Glycogen deposition; 2.5%, Cholangitis; 2.8%, Cholangiohepatitis; 5%, Calcified hydatid cyst; 2.5%, Hepatic abscess; 2.5%, lipofuscin pigments; 17.5%. It is concluded that the highest and lowest prevalent patterns of hepatic lesions were hydatid cysts and Hepatic abscess respectively.

Keywords: camel, liver, lesion, pathology, slaughterhouse

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Authors: Rabab Makki, Deputy Chief Dietitian

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Malnutrition is commonly seen in Liver Disease patients. Prevalence of malnutrition in cirrhosis, is as high as 65-90%. Protein depletion and reduced muscle function are common. There are many mechanisms of malnutrition in liver cirrhosis e.g. insulin resistance, low respiratory quotient, increased glucogenesis etc. Nutrition support improves outcome in patients unable to maintain an intake of 35-40 Kcal/kg and 1.2-1.5 gm/kg/day. Simple methods of assessment such as subjective global assessment, calorie counting, MMC are useful. The value of BCAAs remains uncertain despite a considerable number of studies. Normal protein diets have been given safely to patients with hepatic encephalopathy. Restriction of protein not more than 48 hours pre- and pro-biotic, glutamine, fish oil etc are all part of the latest advanced techniques used.

Keywords: liver cirrhosis, omega 3 for liver disease, nutrition management, malnutrition

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Authors: S. Ameddah, O. Deffa, H. Aissaoui, A. Menad, R. Mekkiou, F. Benayache, S. Benayache

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Acetylhydrazide (ACHD) is a metabolite of the anti-tubercular drug isoniazid (INH) that has been implicated in liver damage. This study was designed to evaluate hapatoprotective of n-BuOH extract of Heliotrpium undulatum (HUBE) in ACHD hepatotoxicity in rats. Hepatic damage was induced by administration of ACHD (300 mg/Kg op). The protection was affected by the administration of HUBE (200 mg/Kg op) for 14 days before ACHD administration, caused a decrease in LPO levels and in the transaminase and ALP levels and restored the GSH and its related enzymes (GPx, GST, GR) (50-62 %). Simultaneous administration of HUBE afforded a partial protection in statue of hepatic GSH conjugating enzymes upon administration of ACHD.

Keywords: heliotrpium undulatum, acetylhydrazide, glutathione conjugating enzymes, oxydatif stress, heaptoprotectif effect

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Authors: Yu Wen Wang, Shyh Ming Kuo, Hsia Ying Cheng, Yu Chiuan Wu

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Liver fibrosis is caused by the activation of hepatic stellate cells in the liver to secrete excessive and deposition of extracellular matrix. In recent years, many treatment strategies have been developed to reduce the activation of hepatic stellate cells and therefore to increase the decomposition of extracellular matrix. Bacopa monnieri, an herbaceous plant of the scrophulariaceae, containing saponins and glycosides, which with antioxidant, anti-inflammation, pain relief and free radical scavenging characteristics. This study was to evaluate the inhibition of hepatic stellate cell activity by Bacopa monnieri extract and its therapeutic potential in treating thioacetamide-induced liver fibrosis in rats. The results showed that the IC50 of Bacopa monnieri extract was 0.39 mg/mL. Bacopa monnieri extract could effectively reduce H2O2-induced hepatic stellate cells inflammation. In the TAA-induced liver fibrosis animal studies, albumin secretion recovered to normal level after treated with Bacopa monnieri extract for 2-w, and fibrosis related proteins, α-SMA and TGF-1levels decreased indicating the extract exerted therapeutic effect on the liver fibrosis. However, inflammatory factors TNF- obviously decreased after 4-w treatment. In summary, we could successfully extract the main component-Bacopaside I from the plant and acquired a potential therapy using this component in treating TAA-induced liver fibrosis in rat.

Keywords: anti-inflammatory, Bacopa monnieri, fibrosis, hepatic stellate cells, water extract

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Authors: Yee Hooi Min, Mohdnasir Abdul Hadi

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Tensioned membrane structure in the form of Enneper minimal surface can be considered as a sustainable development for the green environment and technology, it also can be used to support the effectiveness used of energy and the structure. Soap film in the form of Enneper minimal surface model has been studied. The combination of shape and internal forces for the purpose of stiffness and strength is an important feature of membrane surface. For this purpose, form-finding using soap film model has been carried out for Enneper minimal surface models with variables u=v=0.6 and u=v=1.0. Enneper soap film models with variables u=v=0.6 and u=v=1.0 provides an alternative choice for structural engineers to consider the tensioned membrane structure in the form of Enneper minimal surface applied in the building industry. It is expected to become an alternative building material to be considered by the designer.

Keywords: Enneper, minimal surface, soap film, tensioned membrane structure

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Authors: Hang T. T. Tran, Ha T. Le, Hanh T. P. Tran, Hung V. Cao, Giang T. H. Nguyen, Dien M. Tran, Tobias Alfvén, Linus Olson

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Background: Hypoxic Ischemic Encephalopathy is one of the major causes of neonatal death and those who survive with severe encephalopathy are more likely to develop adverse long-term outcomes such as neurocognitive impairment and cerebral palsy, which is a huge burden, especially in low-middle income countries. It is important to have a long-term follow-up for early detection and promote early intervention for these groups of high-risk infants. Aim: To determine the neurological outcome of cooling infants at 18 months and identify an optimized neurological examination scale for Hypoxic Ischemic Encephalopathy infants in Vietnam. Method: Descriptive study of neurodevelopmental outcomes at 18 months of HIE infants who underwent therapeutic hypothermia treatment in Vietnam. All survived cooling infants were assessed at discharge and at 6, 12, and 18 months by a pediatric physical therapist and a neurologist using two assessment tools: Ages and Stages Questionnaires and the Hammersmith Infant Neurological Examination scale to detect impairments and promote early intervention for those who require it. Results: During a 3-year period, a total of 130 neonates with moderate to severe HIE underwent therapeutic hypothermia treatment using Phase change material mattress (65% moderate, 35% severe – Sarnat). 43 (33%) died during hospitalization and infancy; among survivors, 69 (79%) completed 3 follow-ups at 18 months. At 18 months, 25 had cerebral palsy, 11 had mild delayed neurodevelopment. At each time-point, infants with a normal/mildly delayed neurodevelopment had significantly higher Ages and Stages Questionnaires and Hammersmith Infant Neurological Examination scores (p<0.05) than those with cerebral palsy. Conclusion: The study showed that the Ages and Stages Questionnaires and Hammersmith Infant Neurological Examination is a helpful tool in the process of early diagnosis of infants at low and high neurological risk and identifying those infants needing specific rehabilitation programme.

Keywords: encephalopathy, phase-change-material, neurodevelopment, cerebral palsy

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Authors: S. Som-Am, B. Grechuk

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Moser’s worm problem is the unsolved problem in geometry which asks for the minimal area of a convex region on the plane which can cover all curves of unit length, assuming that curves may be rotated and translated to fit inside the region. We study a version of this problem asking for a minimal convex cover for closed unit curves. By combining geometric methods with numerical box’s search algorithm, we show that any such cover should have an area at least 0.0975. This improves the best previous lower bound of 0.096694. In fact, we show that the minimal area of convex hull of circle, equilateral triangle, and rectangle of perimeter 1 is between 0.0975 and 0.09763.

Keywords: Moser’s worm problem, closed arcs, convex cover, minimal-area cover

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Authors: Ali Kassem

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Background: In the last few years, factors such as insulin resistance (IR) and hepatic steatosis have been linked to progression of hepatic fibrosis.Patients with chronic liver disease, and cirrhosis in particular, are known to be prone to IR. However, chronic HCV (hepatitis C) infection may induce IR, regardless of the presence of liver cirrhosis. Our aims are to study insulin resistance (IR) assessed by HOMA-IR (Homeostatic Model Assessment Insulin Resistance) as a possible risk factor in disease progression in cirrhotic patients and to evaluate the role of IR in hepatic fibrosis progression. The correlations of HOMA-IR values to laboratory, virological and histopathological parameters of chronic HCV are also examined. Methods: The study included 50 people divided into 30 adult chronic hepatitis C patients diagnosed by PCR (polymerase chain reaction) within previous 6 months and 20 healthy controls. The functional and morphological status of the liver were evaluated by ultrasonography and laboratory investigations including liver function tests and by liver biopsy. Fasting blood glucose and fasting insulin levels were measured and body mass index and insulin resistance were calculated. Patients having HOMA-IR >2.5 were labeled as insulin resistant. Results: Chronic hepatitis C patients with IR showed significantly higher mean values of BMI (body mass index) and fasting insulin than those without IR (P < 0.000). Patients with IR were more likely to have steatosis (p = 0.006), higher necroinflammatory activity (p = 0.05). No significant differences were found between the two groups regarding hepatic fibrosis. Conclusion: HOMA-IR measurement could represent a novel marker to identify the cirrhotic patients at greater risk for the progression of liver disease. As IR is a potentially modifiable risk factor, these findings may have important prognostic and therapeutic implications. Assessment of IR by HOMA-IR and improving insulin sensitivity are recommended in patients with HCV and related chronic liver disease.

Keywords: hepatic fibrosis, hepatitis C virus infection, hepatic steatosis, insulin resistance

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Authors: Laura Acevedo-Pacheco, Janet Alejandra Gutierrez-Uribe, Lucia Elizabeth Cruz-Suarez, Segio Othon Serna-Saldivar

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Seaweeds can generate changes in the metabolism of lipids; as a consequence, this may diminish cholesterol and other lipids in the blood. However, the consumption of marine algae may also alter the functions of other organs. Therefore, the objective of this research was to study the effect of two different sorts of algae (Ecklonia arborea and Silvetia compressa) in the metabolism of lipids, as well as, in the physiology of the liver. Wistar male rats were fed for two months with independent diets composed of 20% of fat and 2.5% of E. arborea and S. compressa each. Blood parameters (cholesterol, lipoproteins, triglycerides, hepatic enzymes) and triglycerides in the liver were quantified, and also hepatic histology analyses were performed. While S. compressa reduced 18% total cholesterol compared to the positive control, E. arborea increased it 5.8%. Animals fed with S. compressa presented a decrement, compared to the positive control, not only in low density lipoproteins levels (53%) but also in triglycerides (67%). The presence of steatosis in the histologies and the high levels of triglycerides showed an evident lipid accumulation in hepatic tissues of rats fed with both algae. These results indicate that even though S. compressa showed a promising resource to decrease total cholesterol and low-density lipoproteins in blood, a detrimental effect was observed in liver physiology. Further investigations should be made to find out if toxic compounds associated with these seaweeds may cause liver damage especially in terms of heavy metals.

Keywords: brown algae, Eisenia arborea, hepatic metabolism, lipidemic metabolism, Pelvetia compressa, steatosis

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Authors: Khaled S. Al Salhen

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Aldehyde oxidase is molybdo-flavoenzyme involved in the oxidation of hundreds of endogenous and exogenous and N-heterocyclic compounds and environmental pollutants. Uncharged N-heterocyclic aromatic compounds such phenanthridine are commonly distributed pollutants in soil, air, sediments, surface water and groundwater, and in animal and plant tissues. Phenanthridine as uncharged N-heterocyclic aromatic compound was incubated with partially purified aldehyde oxidase from rainbow trout fish liver. Reversed-phase HLPC method was used to separate the oxidation products from phenanthridine and the metabolite was identified. The 6(5H)-phenanthridinone was identified the major metabolite by partially purified aldehyde oxidase from fish liver. Kinetic constant for the oxidation reactions were determined spectrophotometrically and showed that this substrate has a good affinity (Km = 78 ± 7.6 µM) for hepatic aldehyde oxidase, coupled with a relatively high oxidation rate (0.77± 0.03 nmol/min/mg protein). In addition, the kinetic parameters of hepatic fish aldehyde oxidase towards the phenanthridine substrate indicate that in vitro biotransformation by hepatic fish aldehyde oxidase will be a significant pathway. This study confirms that partially purified aldehyde oxidase from fish liver is indeed the enzyme responsible for the in vitro production 6(5H)-phenanthridinone metabolite as it is a major metabolite by mammalian aldehyde oxidase.

Keywords: aldehyde oxidase, fish, phenanthridine, specificity

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Authors: Alaa E. El-sisi, Sherin Zakaria

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Rebamipide is an antiulcer drug with unique properties such as anti-inflammatory action. It induces endogenous prostaglandin e2 (PGE2). PGE2 is considered as a potent physiological suppressor of liver fibrosis. Aim of study: This study investigated the effect of rebamipide on hepatic fibrosis. Material and Method: Hepatic fibrosis was induced by intraperitoneal injections (IP) injection of CCl4 (0.45 mL/kg) in corn oil 1:5 twice a week for 4 weeks. Rats were divided into four groups as follow: Group 1 treated with CCL4 only, group 2 and 3 treated with CCL4 and rebamipide 60 mg/kg/day (group2) or 100 mg/kg/day (group3), and the fourth group was considered as control group and treated with vehicles. ALT, AST, and Bilirubin were assayed in serum. Antioxidant markers such as malondialdhyde (MDA) and superoxide dismutase (SOD) and fibrotic markers such as hyaluronic acid (HA) and procollagen-III (procol-III) were evaluated in liver tissues. IL-10 as well as PGE2 were also assayed in liver tissues. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen precipitation in liver tissues was visualized using masson trichrom stain. Results: Rebamipide inhibit CCL4 induced increase in ALT and AST significantly (p < 0.05). Rebamipide exerted an antioxidant effect as it inhibits CCL4 induced increased MDA level and decreased SOD activity. Fibrotic markers assay revealed that repamipide (60 or 100 mg/kg/day) decreased the level of procol-III and HA compared to CCl4 (p < 0.05). Oral administration of Rebamipide was associated with a significant increase (p < 0.05) of PGE2 and IL-10. Rebamipide especially at the dose of (100 mg/kg/day) restores liver histology structure and abolish collagen precipitation in liver tissues. Conclusion: Rebamipide retards hepatic fibrosis induced by CCL4 may be through the induction of PGE2 level.

Keywords: fibrotic markers, hepatic fibrosis, PGE2, rebamipide

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Authors: Tae-Hoon Kim, Kwon-Ha Yoon, Hong Young Jun, Ki-Jong Kim, Young Hwan Lee, Myeung Su Lee, Keum Ha Choi, Ki Jung Yun, Eun Young Cho, Yong-Yeon Jeong, Chung-Hwan Jun

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Purpose: To assess the changes of hepatic metabolite for differentiation between non-alcoholic steatohepatitis (NASH) and simple steatosis on proton magnetic resonance spectroscopy (1H-MRS) in both humans and animal model. Methods: The local institutional review board approved this study and subjects gave written informed consent. 1H-MRS measurements were performed on a localized voxel of the liver using a point-resolved spectroscopy (PRESS) sequence and hepatic metabolites of alanine (Ala), lactate/triglyceride (Lac/TG), and TG were analyzed in NASH, simple steatosis and control groups. The group difference was tested with the ANOVA and Tukey’s post-hoc tests, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristics (ROC) curve. The associations between metabolic concentration and pathologic grades or non-alcoholic fatty liver disease(NAFLD) activity scores were assessed by the Pearson’s correlation. Results: Patient with NASH showed the elevated Ala(p<0.001), Lac/TG(p < 0.001), TG(p < 0.05) concentration when compared with patients who had simple steatosis and healthy controls. The NASH patients were higher levels in Ala(mean±SEM, 52.5±8.3 vs 2.0±0.9; p < 0.001), Lac/TG(824.0±168.2 vs 394.1±89.8; p < 0.05) than simple steatosis. The area under the ROC curve to distinguish NASH from simple steatosis was 1.00 (95% confidence interval; 1.00, 1.00) with Ala and 0.782 (95% confidence interval; 0.61, 0.96) with Lac/TG. The Ala and Lac/TG levels were well correlated with steatosis grade, lobular inflammation, and NAFLD activity scores. The metabolic changes in human were reproducible to a mice model induced by streptozotocin injection and a high-fat diet. Conclusion: 1H-MRS would be useful for differentiation of patients with NASH and simple hepatic steatosis.

Keywords: non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, 1H MR spectroscopy, hepatic metabolites

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Authors: S. H. Jang

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Posterior reversible encephalopathy syndrome (PRES) is characterized by acute neurologic symptoms (visual loss, headache, altered mentality and seizures) and by typical imaging findings (bilateral subcortical and cortical edema with predominatly posterior distribution). Nephrotic syndrome is a syndrome comprising signs of proteinuria, hypoalbuminemia, and edema. It is well known that hypertension predispose patient with nephrotic syndrome to PRES. A 45-year old male was referred for suddenly developed vertigo, disequilibrium. He had previous history of nephrotic syndrome. His medical history included diabetes controlled with medication. He was hospitalized because of generalized edema a few days ago. His vital signs were stable. On neurologic examination, his mental state was alert. Horizontal nystagmus to right side on return to primary position was observed. He showed good grade motor weakness and ataxia in right upper and lower limbs without other sensory abnormality. Brain MRI showed increased signal intensity in FLAIR image, decreased signal intensity in T1 image and focal enhanced lesion in T1 contrast image at whole midbrain, pons and cerebellar peduncle symmetrically, which was compatible with vasogenic edema. Laboratory findings showed severe proteinuria and hypoalbuminemia. He was given intravenous dexamethasone and diuretics to reduce vasogenic edema and raise the intra-vascular osmotic pressure. Nystagmus, motor weakness and limb ataxia improved gradually over 2 weeks; He recovered without any neurologic symptom and sign. Follow-up MRI showed decreased vasogenic edema fairly. We report a case of brain stem PRES in normotensive, nephrotic syndrome patient.

Keywords: posterior reversible encephalopathy syndrome, MRI, nephrotic syndrome, vasogenic brain edema

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Authors: Chittapon Jantararussamee, Malai Taweechotipatr, Udomsri Showpittapornchai, Wisuit Pradidarcheep

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Hepatic fibrosis is characterized by collagen accumulation in hepatic lobules following wound healing process. If lefts untreated, it could progress into hepatic cirrhosis, portal hypertension, and liver failure. Probiotics comprise of lactic acid bacteria which are crucial components of the intestinal microflora and possess many beneficial properties. The objective of this study is to investigate the hepatoprotective effects of probiotic lactic acid bacteria (mixture of Lactobacillus paracasei, Lactobacillus casei, and Lactobacillus confusus at a ratio of 1: 1: 1) on thioacetamide-induced liver fibrotic rats in term of histomorphology study. Twenty-four male Wistar rats were randomly divided into four groups with 6 rats each: (A) control, (B) fibrotic, (C) fibrotic+probiotic, and (D) probiotic. Group (A) received daily oral administration of distilled water. Group (B and C) were induced by intraperitoneal injection of thioacetamide (TAA) (200 mg/kg BW) 3 times per week for consecutive 8 weeks. In probiotic-treated group (C and D), the number of a mixture of the viable microbial cells at 10⁹ CFU/ml was administered orally daily. After sacrifice, liver tissues were collected and processed for routine histological technique and stained with Sirius red. It was found that the fibrotic rats showed hepatic injury marked by area of inflammation, hydropic degeneration of hepatocytes, and accumulation of myofibroblast-like cells. The collagen fibers were substantially accumulated in the hepatic lobules. Moreover, probiotic-treated group significantly reduced the accumulation of collagen in rats treated by TAA. The liver damage was found to be lesser in the probiotic-treated group. It was noted that the liver tissues of control and probiotics groups were shown to be normal. Administration with probiotic lactic acid bacteria could improve the histomorphology in fibrotic liver and be useful for prevention of hepatic disorders.

Keywords: liver fibrosis, probiotics, lactic acid bacteria, thioacetamide

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Authors: Aadil Khan, Yasser Chomayil, P. P. Venugopalan

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Background: Budd-Chiari syndrome is caused by thrombosis of the hepatic veins and/or the thrombosis of the intrahepatic or suprahepatic IVC. The etiology remains idiopathic in 16% -35% of cases. Malignancy, rheumatological disorder, myeloproliferative disease, inheritable coagulopathy, infection or hyperestrogen state can be identified in many cases. Methodology: Review of case records of the patient presented to Aster Medcity, Emergency Department, Cochin. Introduction:17 years old female was presented to ED with fever, jaundice and abdominal distention since 1 week. O/E: Pallor+, icterus+. Abdomen- gross distension+, shifting dullness+, generalized anasarca+. USG abdomen showed hepatomegaly with mild coarse echotexture and moderate to gross ascites. CT abdomen and chest showed hepatomegaly with thrombosis of all three hepatic vein and moderate ascites suggestive of Budd-Chiari syndrome. Patient was taken for catheter vein thrombolysis. Venogram done the next day revealed almost > 50% opening of the right hepatic vein. Concurrent doppler showed colour and doppler signals in middle hepatic veins. She gradually improved and was discharged home on anticoagulant and adviced regular follow up. Conclusion: Being a rare disease in this young population, high suspicion is required when evaluating young patients with abdominal pain and jaundice.

Keywords: Budd-Chiari syndrome, rare disease, abdominal pain, India

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Authors: Ana Carolina Kogawa, Selma Gutierrez Antonio, Hérida Regina Nunes Salgado

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Rifaximin is an oral antimicrobial, gut - selective and not systemic with adverse effects compared to placebo. It is used for the treatment of hepatic encephalopathy, travelers diarrhea, irritable bowel syndrome, Clostridium difficile, ulcerative colitis and acute diarrhea. The crystalline form present in the rifaximin with minimal systemic absorption is α, being the amorphous form significantly different. Regulators are increasingly attention to polymorphisms. Polymorphs can change the form by altering the drug characteristics compromising the effectiveness and safety of the finished product. International Conference on Harmonization issued the ICH Guidance Q6A, which aim to improve the control of polymorphism in new and existing pharmaceuticals. The objective of this study was to obtain polymorphic forms of rifaximin employing recrystallization processes and characterize them by thermal analysis (thermogravimetry - TG and differential scanning calorimetry - DSC), X-ray diffraction, scanning electron microscopy and solubility test. Six polymorphic forms of rifaximin, designated I to VI were obtained by the crystallization process by evaporation of the solvent. The profiles of the TG curves obtained from polymorphic forms of rifaximin are similar to rifaximin and each other, however, the DTG are different, indicating different thermal behaviors. Melting temperature values of all the polymorphic forms were greater to that shown by the rifaximin, indicating the higher thermal stability of the obtained forms. The comparison of the diffractograms of the polymorphic forms of rifaximin with rifaximin α, β and γ constant in patent indicate that forms III, V and VI are formed by mixing polymorph β and α and form III is formed by polymorph β. The polymorphic form I is formed by polymorph β, but with a significant amount of amorphous material. Already, the polymorphic form II consists of polymorph γ, amorphous. In scanning electron microscope is possible to observe the heterogeneity of morphological characteristics of crystals of polymorphic forms among themselves and with rifaximin. The solubility of forms I and II was greater than the solubility of rifaximin, already, forms III, IV and V presented lower solubility than of rifaximin. Similarly, the bioavailability of the amorphous form of rifaximin is considered significantly higher than the form α, the polymorphic forms obtained in this work can not guarantee the excellent tolerability of the reference medicine. Therefore, studies like these are extremely important and they point to the need for greater requirements by the regulatory agencies competent about polymorphs analysis of the raw materials used in the manufacture of medicines marketed globally. These analyzes are not required in the majority of official compendia. Partnerships between industries, research centers and universities would be a viable way to consolidate researches in this area and contribute to improving the quality of solid drugs.

Keywords: electronic microscopy, polymorphism, rifaximin, solubility, X-ray diffraction

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Authors: Carl Eiselen, Stephen O’Hagan

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Background: Q fever, caused by the obligate intracellular bacterium Coxiella burnetii, is an infectious disease with variable systemic manifestations. Its potential to cause ocular complications has not been reported before in Australia. This case study explores the unusual presentation of asymptomatic acute multifocal retinitis (AMR) in a patient with acute Q fever endocarditis and hepatitis in rural Queensland, Australia. Case Presentation: A 48-year-old male gardener presented with flu-like symptoms, weight loss, and encephalopathy. Despite systemic malaise, he had no ocular symptoms. Laboratory investigations confirmed acute Q fever, and imaging studies identified hepatic involvement and endocarditis. The retinal screening revealed asymptomatic AMR, corroborated by fundus examination and SD-OCT. Following treatment with Doxycycline and hydroxychloroquine, both systemic and ocular manifestations improved. Discussion: This is the first documented case of asymptomatic AMR associated with Q fever. The patient’s lack of autoantibodies challenges the established understanding of Q fever endocarditis and suggests potential alternative mechanisms. Conclusion: This case report expands our understanding of the multi-systemic impact of Q fever, highlighting the need for comprehensive clinical evaluation and including retinal screening in the setting of acute infection. The disease's underlying mechanism for ocular involvement is not yet established.

Keywords: Coxiella Burnetti, Q fever, ocular manifestation, acute multifocal retintis, endocarditis

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Authors: Belgherbi Aicha, Hadjidj Ismahen, Bessaid Abdelhafid

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The interpretation of medical images benefits from anatomical and physiological priors to optimize computer- aided diagnosis applications. Segmentation of liver and liver lesion is regarded as a major primary step in computer aided diagnosis of liver diseases. Precise liver segmentation in abdominal CT images is one of the most important steps for the computer-aided diagnosis of liver pathology. In this papers, a semi- automated method for medical image data is presented for the liver and liver lesion segmentation data using mathematical morphology. Our algorithm is currency in two parts. In the first, we seek to determine the region of interest by applying the morphological filters to extract the liver. The second step consists to detect the liver lesion. In this task; we proposed a new method developed for the semi-automatic segmentation of the liver and hepatic lesions. Our proposed method is based on the anatomical information and mathematical morphology tools used in the image processing field. At first, we try to improve the quality of the original image and image gradient by applying the spatial filter followed by the morphological filters. The second step consists to calculate the internal and external markers of the liver and hepatic lesions. Thereafter we proceed to the liver and hepatic lesions segmentation by the watershed transform controlled by markers. The validation of the developed algorithm is done using several images. Obtained results show the good performances of our proposed algorithm

Keywords: anisotropic diffusion filter, CT images, hepatic lesion segmentation, Liver segmentation, morphological filter, the watershed algorithm

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Authors: Hirokatsu Kawashima

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In an attempt to elucidate relationships between listening to music and pronunciation learning, a classroom-based investigation was conducted with Japanese EFL learners (n=45). The subjects were instructed to listen to English songs they liked on YouTube, especially paying attention to phonologically similar vowel and consonant minimal pair words (e.g., live and leave). This kind of activity, which included taking notes, was regularly carried out in the classroom, and the same kind of task was given to the subjects as homework in order to reinforce the in-class activity. The duration of these activities was eight weeks, after which the program was evaluated on a 9-point scale (1: the lowest and 9: the highest) by learners’ self-evaluation. The main questions for this evaluation included 1) how good the learners had been at pronouncing vowel and consonant minimal pair words originally, 2) how often they had listened to songs good for pronouncing vowel and consonant minimal pair words, 3) how frequently they had moved their mouths to vowel and consonant minimal pair words of English songs, and 4) how much they thought the program would support and enhance their pronunciation learning of phonologically similar vowel and consonant minimal pair words. It has been found, for example, A) that the evaluation of this program is by no means low (Mean: 6.51 and SD: 1.23), suggesting that listening to music may support and enhance pronunciation learning, and B) that listening to consonant minimal pair words in English songs and moving the mouth to them are more related to the program’s evaluation (r =.69, p=.00 and r =.55, p=.00, respectively) than listening to vowel minimal pair words in English songs and moving the mouth to them (r =.45, p=.00 and r =.39, p=.01, respectively).

Keywords: minimal pair, music, pronunciation, song

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Authors: Irfana M., Priyandi Kabasi

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Children with specific language impairment (SLI) have difficulty acquiring and using language despite having all the requirements of cognitive skills to support language acquisition. These children have normal non-verbal intelligence, hearing, and oral-motor skills, with no history of social/emotional problems or significant neurological impairment. Nevertheless, their language acquisition lags behind their peers. Phonological complexity can be considered to be the major factor that causes the inaccurate production of speech in this population. However, the implementation of various ranges of complex phonological stimuli in the treatment session of SLI should be followed for a better prognosis of speech accuracy. Hence there is a need to study the levels of phonological complexity. The present study consisted of 7 individuals who were diagnosed with SLI and 10 developmentally normal children. All of them were Hindi speakers with both genders and their age ranged from 4 to 5 years. There were 4 sets of stimuli; among them were minimal contrast vs maximal contrast nonwords, minimal coarticulation vs maximal coarticulation nonwords, minimal contrast vs maximal contrast words and minimal coarticulation vs maximal coarticulation words. Each set contained 10 stimuli and participants were asked to repeat each stimulus. Results showed that production of maximal contrast was significantly accurate, followed by minimal coarticulation, minimal contrast and maximal coarticulation. A similar trend was shown for both word and non-word categories of stimuli. The phonological complexity effect was evident in the study for each participant group. Moreover, present study findings can be implemented for the management of SLI, specifically for the selection of stimuli.

Keywords: coarticulation, minimal contrast, phonological complexity, specific language impairment

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Authors: Feng Zhang, Li Chen, Desong Kong, Xiaoping Zhang, Xiaojing Zhu, Yin Lu, Shizhong Zheng

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Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.

Keywords: angiogenesis, hepatic stellate cell, curcumin, peroxisome proliferator-activated receptor-γ

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Authors: Jeffey George, Varghese Thomas

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Background and Objectives: PHG is an important source of gastrointestinal bleeding in patients with portal hypertension. Aim: To assess the progression to severe portal hypertensive gastropathy(PHG) in patients with cirrhosis who were treated with maximum tolerated dose of propranalol, after variceal eradication to grade II or below. Methods: Cirrhotic patients(child A and B) presenting with upper gastrointestinal bleeding with endoscopic findings of mild or no PHG were followed up over 6 months after variceal eradication to assess the progression to severe PHG. Included patients were randomised to either maximum tolerated doses of propranalol (group A) or to no treatment (group B). Primary end point of the study were the development of gastrointestinal bleed, evidence of hepatic decompensation and death. Progression to severe PHG were compared between the two groups. Results: 56 patients (49 males) were enrolled (group A = 28, group B = 28). 8 patients were excluded from final analysis (gi bleed=5, encephalopathy=2,HCC=1 including 4 deaths).3 patients were lost to follow-up, and 1 developed intolerance to propranalol. Mean dose of propranalol used was 60 mg per day. Progression to severe PHG in the fundus over 6 months was 23.8% in group A versus 15.8 % in group B (p = 0.52). Severe PHG was noted in body in 14.3% in group A versus 21.1% in group B (p = 0.57). 23.8 % in group A had progression to severe PHG compared with 15.8 % in group B (p =0.52). There was no statistically significant difference in the progression of PHG between the two groups(p=0.43). Conclusion: In this short term study propranalol was found not to prevent the progression to severe portal hypertensive gastropathy in cirrhotic patients who had undergone endotherapy for esophageal varices.

Keywords: propranalol, portal hypertensive gastropathy, cirrhotic patients, gastroenterology

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