Las enfermedades metabólicas del hígado / Metabolic liver diseases / Doenças metabólicas hepáticas

El hígado humano, órgano unitario con múltiples funciones vitales, ocupa una posición anatómica privilegiada y estratégica, que le permite recibir información del resto de los órganos y sistemas de la economía. Es posible estar ante una enfermedad hepática con probables complicaciones sistémicas o frente a trastornos extrahepáticos que pueden afectar el hígado. Tal es el caso de las alteraciones en el metabolismo de determinados sustratos que tienen un impacto directo en este órgano y que ocasionan enfermedades hepáticas diversas. Así, se mencionan entre otras: la deficiencia de alfa 1 antitripsina (glicoproteína) que produce colestasis neonatal y cirrosis hepática en adolescentes y adultos con potencial desarrollo de hepatocarcinoma, y la alteración del metabolismo de ciertos metales como el cobre y el hierro, los que al acumularse en el hígado (sobrecarga hepática), dan por resultado las enfermedades de Wilson y hemocromatosis, respectivamente. Estas enfermedades metabólicas, si bien son de baja frecuencia en Argentina, y algunas de ellas difícilmente diagnosticadas en todo el mundo, pueden derivar en una muerte temprana. Esta breve revisión tiene como objetivo enfatizar que las enfermedades metabólicas que afectan al hígado no son una rareza y que pueden presentarse en diversas formas, y así mimetizarse con otras hepatopatías. Lo importante es tenerlas siempre presente.

Human liver, an extraordinary organ with multiple vital functions, takes up a privileged anatomic position, whose strategic site enables it to receive information from the rest of the organism. It is possible to observe liver disease with probable systemic complications, or extrahepatic manifestations that can affect the liver.They could be overthrow metabolisms because of some substances with a direct impact on the gland leading to different liver diseases. Such is the case of Alpha 1 antitrypsin deficiency (a glycoprotein deficiency) which leads to neonatal colestasis and cirrhosis in young and adults, and potentially develop hepatocellular carcinoma. Copper and ironmetabolisms and their accumulation load the hepatocites as a result give rise to Wilson disease and hemochromatosis, respectively. These metabolic diseases, of less frequency in Argentina, are hard to be diagnosed world wide and can lead to premature death. This short revision is aimed at emphasizing that metabolic diseases are not rare and can mimicry different liver diseases.

O fígado humano, órgão unitário com múltiplas funções vitais, ocupa uma posição anatômica privilegiada e estratégica, o que lhe permite receber informações do resto dos órgãos e sistemas da economia. É possível estar diante de uma doença hepática com prováveis complicações sistêmicas ou perante distúrbios extra hepáticos que podem afetar o fígado. Tal é o caso das alterações no metabolismo de certos substratos que têm um impacto direto neste órgão, causando diversas doenças hepáticas. Deste modo, são mencionadas, dentre outras: a deficiência de alfa 1 antitripsina (glicoproteína) que produz colestase neonatal e cirrose hepática nos adolescentes e adultos com potencial desenvolvimento de hepatocarcinoma e a alteração do metabolismo de certos metais como o cobre e o ferro, os quais ao se acumularem no fígado (sobrecarga hepática), resultam nas doenças de Wilson e Hemocromatose, respectivamente. Estas doenças metabólicas, apesar de serem de baixa frequência na Argentina, e algumas delas dificilmente diagnosticadas em todo o mundo, podem levar à morte precoce. Esta breve revisão visa enfatizar que as doenças metabólicas que afetam o fígado não são uma raridade e podem se apresentar de várias formas, mimetizando-se com outras hepatopatias. O importante é que estejam sempre presentes.

Nodular histiocytic/mesothelial hyperplasia: a clinicopathologic analysis of 7 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathologic and immunohistochemical features of nodular histiocytic/mesothelial hyperplasia (NHMH) and to improve the knowledge of this disease.</p><p><b>METHODS</b>Seven cases of NHMH were collected and the clinicopathologic and immunohistochemical data were analyzed with review of the literature.</p><p><b>RESULTS</b>Seven male patients aged from 1.5 to 5.0 years (mean 2.8). The main clinical symptom was an inguinal mass.Grossly, main pathological changes were the mural nodule or free nodule in lumen, with diameter of 0.1-0.5 cm.Histologically, the tumor cell morphology was relatively single, cohesive polygonal or oval cells which were arranged in solid sheets or nests, usually with ovoid or deeply grooved nuclei and a moderate amount of pale pink cytoplasm in the nodular collection area. The nuclei had delicate chromatin and no obvious atypia, and mitosis was incidentally found. A few scattered lymphocytes were found in the stroma. The cyst wall was lined by a single layer of mesothelial cells.Immunohistochemically, the most cells in nodular lesion were strongly positive for the histiocytic marker CD68, vimentin and α1-antichymotrypsin, while lining mesothelial cells on the wall were positive for calretinin, MC, WT1, CK5/6, CKpan and EMA.</p><p><b>CONCLUSIONS</b>NHMH is a rare and benign tumor-like lesion, and easy to be misdiagnozed, which should be distinguished from neuroendocrine tumors, Langerhans cell histiocytosis, seminoma, mesothelioma and so on. The correct diagnosis of this lesion depends on the clinical characteristics, morphology and immunohistochemistry.</p>

Clinical features and prognosis of solid-pseudopapillary tumor of the pancreas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the clinicopathological and immunohistochemical features, histogenesis and biological behavior, clinical treatment and prognosis of solid pseudopapillary tumor of the pancreas (SPT).</p><p><b>METHODS</b>Routine HE and immunohistochemical (SP) stainings were used in the pathological examination of 18 cases of SPT. Their clinical data were retrospectively analyzed. All the 18 postoperative patients were followed-up for 3 months to 10 years with an average of 29.2 months.</p><p><b>RESULTS</b>There were 16 females and 2 males, age ranging from 9 to 65 years with mean age of 25.3 years. Abdominal pain and palpable mass were among the major complains. Tumors were encapsulated and mixed with solid and cystic tissues. Histological features were pseudopapillary structure with a fibrovascular core. Immunhistologically, most tumors were positive for alpha-AT, alpha-ACT and Vim, with a high percentage of 94.4%. The eighteen cases were followed-up from 3 to 120 months. Five cases received reoperation after recurrence, and 14 cases were alive. Maximum survival time was 121 months and the minimum survival time was 3 months, with a median survival time of 23.0 months. The 5-year survival rate was 72.2%. A Kaplan-Meier analysis revealed that patient's age, tumor size, pathologic features, metastasis were major prognostic factors for SPT.</p><p><b>CONCLUSION</b>SPT is a tumor of low-grade malignancy and may be derived from multipotent stem cells. SPT most frequently affects young female, and has distinct clinicopathologic manifestation with excellent prognosis after surgical treatment.</p>

Haematologial manifestations in HCV infected patients at Sharkia Governerate, Egypt

The aim of this study was to evaluate the hematological manifestations occurring in patients suffering from chronic hepatitis C virus [HCV] infection. Positive HCV-RNA cases [109] were subjected to complete blood count [CBC], prothrombin time [PT], partial thromboplastin time [PTT], bleeding time [BT], coagulation time [CT], detection of fibrinogen degradation products [FDPs], measurement of plasma alpha- antitrypsin [AAT], then bone marrow [BM] aspiration and examination for 20 cases. The patients were classified into three groups according to the histopathological staging and grading of liver biopsy. The comparison between groups according to histopathological grading and staging for hematological and chemical parameters revealed a significant statistical difference in platelets count, S albumin, ALT and AST levels. The comparison between groups according to histopathological grading and staging for coagulation profile, AAT level and FDPs revealed a significant statistical difference between all parameters. Bone marrow aspiration and examination revealed mild hypocellularity with an increased number of lymphocytes and a relevance of plasmacytoid-lymphocytes

Lipid profile in smokers and non-smokers associated with pulmonary emphysema

The changes in lipid profile and lipid peroxidation in smoking and non-smoking subjects associated with emphysema and their effects on heart were investigated. Forty male subjects were selected and classified clinically into four groups; control, cigarette smoking subjects without emphysema, non-smoking subjects with emphysema, and cigarette smoking subjects with emphysema. Serum thiobarbituric acid reactive substances [TBARS] were assessed as a direct indicator of lipid peroxidation. Serum total lipid, total cholesterol, triglycerides, high density lipoprotein-cholesterol [HDL-C], and low density lipoprotein-cholesterol [LDL-C] were evaluated. Serum creatine kinase [CK] activity was assessed as a direct indicator of heart injury. Serum alpha-1-antitrypsin [AAT] level was measured as an indicator of emphysema. As compared to control, emphysematous and non-emphysematous groups showed alteration in lipid profile including significant increase in all lipid components, except HDL-C. In comparison with smoking group without emphysema, all lipid components revealed no significant change in non-smoking subjects with emphysema, while a sign of lipid impairments was high in cigarette smoking group with emphysema as compared to smoking group without emphysema. The level of TBARS and CK activity were higher in the two groups with emphysema as compared to either controls or smoking subjects without emphysema. In contrast, the AAT levels were low in the two groups with emphysema as compared to controls and smoking subjects without emphysema. It is clear from the foregoing findings that emphysema, especially in smoking subjects, was mainly associated with oxygen- derived free radicals that damage lipids in peribronchiolar alveoli of the lung tissues accompanied with elevation in total lipid, triglyceride, total cholesterol, LDL-C levels, that may lead to the high risk of heart diseases

Apolipoprotein E Gene and Alpha 1-Antichymotrypsin Gene in Brain of Sporadic Alzheimer's Disease

BACKGROUND: This study aims to detect any causative genetic alterations and to demonstrate any correlations of these genes in the pathogenesis of mostly late-occurring sporadic type of Alzheimer's disease (AD). METHODS: A total of 67 registered cases of autopsy-confirmed brain tissues were analyzed. Included here was sporadic AD (n=41), vascular dementia (n=17), and non-demented physiologically aging control brains (n=9). ApoE genotyping was done with the enzymatic digestion, and allele specific PCR was done to analyze the -491 A/T polymorphism of ApoE. Detection of polymorphism of alpha 2-macroglobulin (A2M) was done with enzymatic digestion and DNA sequencing. RT-PCR products were electrophoresed to detect mRNA expression of alpha 1-antichymotrypsin (ACT). RESULTS: A prevalence rate of ApoE E4 genotype (E3/E4, E4/E4) showed significantly higher in patients with AD than in patients with vascular dementia (43.8% vs. 11.7%, p=0.019). Only 1 out of 4 cases of sporadic AD was associated with the E4/E4 allele. -491A/ T polymorphism of the ApoE promoter was found only in AD (2/41 cases, 4.9%). The incidence of heterozygous allelic polymorphism with 5 bp deletions in exon 18 of A2M-2 was 4.9% (2 out of 41) in AD. Messenger RNA expression of ACT, which is closely associated with the ApoE E4 allele, was increased in AD in comparison with normal control (p=0.0002). CONCLUSIONS: ApoE4 genotype and ACT are closely related to the pathogenesis of late-onset sporadic AD. Neither -491 polymorphism of ApoE promoter nor A2M-2 showed close association with AD in these brain samples.

Intestinal absorptive status and gut contamination among Egyptian thalassemic children

In this study, the intestinal absorptive status and the prevalence of small bowel bacterial overgrowth were assessed in 72 thalassemic children. They were classified according to the onset of the disease, the splenic status and type of chelation therapy into three groups. Group I included 15 newly diagnosed cases. Group II included 30 thalassemic children receiving subcutaneous desferrioxamine [DF] as a chelation therapy [15 of them had intact spleen and 15 were splenectomized]. Group III included 27 patients receiving oral salicylhydroxamic acid [SHAM] as a chelation therapy [12 of them had intact spleen and 15 were splenectomized]. Fifteen healthy age and sex matched children served as controls. The results revealed that the levels of fecal alpha-1 antitrypsin [a marker of enteric protein loss] were significantly higher in all studied groups as compared with the control group. In conclusion, malabsorption was a common finding in thalassemic patients regardless of the duration, type of chelation therapy and whether splenectomized or not. Furthermore, small bowel bacterial overgrowth was also common in thalassemic cases, especially the splenectomized ones due to the profound immune disturbances occurring after splenectomy

Malignant Fibrous Histiocytoma of the Liver

Primary sarcomas of the liver are rare. A case of primary malignant fibrous histiocytoma of the liver is reported. A 55-year-old male was admitted with epigastric pain. An abdominal computed tomographic scan disclosed a 10cm, low-density area in the left lobe of the liver. Histological examination of the resected tumor showed bundles of spindle cells arranged in a storiform pattern. In some areas, many bizarre giant cells were scattered. Immunohistochemically, tumor cells were positive for alpha 1-antitrypsin and alpha 1-antichymotrypsin, and weakly positive for vimentin. The tumor cells did not express cytokeratin, desmin or alpha fetoprotein.

Tumores malignos de células germinativas do ovário: expressäo de enolase Neurônio-específica, alfa-1-antitripsina e alfa-1-antiquimotripsina / Malignant tumors of germinoma: expression of phosphopyruvate, alpha 1-antitrypsin and alpha 1-antichymotrypsin

Foi realizado um estudo imuno-histoquímico para verificar a expressäo de enolase neurônio-específica (NSE), alfa 1-antitripsina (AAT) e alfa 1-antiquimotripsina (AAQT) em tumores malignos de células germinativas do ovário. As reaçöes imuno-histoquímicas foram realizadas em tecidos previamente fixados em formol e embebidos em parafina de sete disgerminomas, três tumores do seio endodérmico, três teratomas imaturos e um oriocarcinoma. Todos os tumores, exceto o coriocarcinoma, expressaram NSE. As reaçös com anticorpos anti-AAT e AAQT foram positivas em todos os tipos histológicos dos tumores. Estes dados sugerem que NSE, AAT ou AAQT podem ser mais um marcador para os tumores de células germinativas do ovário.

Serum protease inhibitors in opisthorchiasis, hepatoma, cholangiocarcinoma, and other liver diseases.

Serum alpha 1-antitrypsin, alpha 1-antichymotrypsin and alpha 2-macroglobulin increased significantly in patients suffering from liver diseases: hepatoma, amoebic liver abscess, hepatitis, hepatic cirrhosis, cholangiocarcinoma, carcinoma of the head of pancreas including liver fluke infection (opisthorchiasis). Marked increase of alpha 1-antitrypsin and alpha 1-antichymotrypsin were found in cholangiocarcinoma, carcinoma of the head of pancreas, amoebic liver abscess, hepatic cirrhosis and hepatoma. alpha 2-macroglobulin increased markedly in hepatic cirrhosis. The concentrations of protease inhibitors found in opisthorchiasis were only moderately elevated.

Trypsin and chymotryosin inhinitor of Vigna unguiculata seeds - involvement of tyrosyls in its interaction with proteases

When trypsin and chymotrypsin inhibitor of Vigna unguiculata seeds (black-eyed pea trypsin and chymotrypsin inhibitor, BTCI) combines with ß-trysin, 4.0, 1.5, 5.0, 5.8, and 6.6 tyrosyl residues are shield from reaction with N-acetylimidazole, at reagent/protein molar ratios of 60, 120, 200, 350 and 500, respectively. This may result from the presence of tyrosyl residues in the zone of contact between enzyme and inhibitor. In the interaction of BTCI and alpha-chymotrypsin, only 0.6 tyrosyl residues are shielded from the reaction with N-acetylimidazole, at a 500-fold reagent molar excess

An infrared spectroscopic study on the secondary structure of the black-eyed pea trypsin and chymotrypsin inhibitor - amide I-III and V bands

The infrared spectrum of native black-eyed pea trypsin and chymotrypsin inhibitor (BTCI) in solid film was measured from 550 to 1750 cm-1 and amide I-III, and V regions have been analyzed. By comparison between the observed bands with the modes calculated for several structures (available inthe literature), the occurrence in BTCI of unordered, antipatallel ß-sheet, and ß-turn structures is suggested

Serum alpha-1 antichymotrypsin is a possible growth inhibitor of Plasmodium falciparum.

Serum protease inhibitors were determined in paired sera from 7 patients with cerebral malaria and 2 patients with acute malaria showing high and low growth inhibition activity in the initial and follow-up sera respectively. Alpha-1 antichymotrypsin and alpha-1 antitrypsin but not alpha-2 macroglobulin showed direct correlation with the growth inhibition activity. When alpha-1 antitrypsin was deliberately added to the malarial culture no growth inhibition occurred indicating that the alpha-1 antichymotrypsin was the most likely factor responsible for inhibition of growth of malarial parasites in vitro.