Focal Necrosis In Liver Research Articles

The neonatal liver hosts a spontaneously occurring neutrophil population, exhibiting distinct spatial and functional characteristics from adults.

The elusive nature of the liver immune system in newborns remains an important challenge, casting a shadow over our understanding of how to effectively treat and prevent diseases in children. Therefore, deeper exploration into the intricacies of neonatal immunology might be crucial for improved pediatric healthcare. Using liver intravital microscopy, we unveiled a significant population of granulocytes in the hepatic parenchyma of fetuses and newborns. Utilizing high-dimensional immunophenotyping, we showed dynamic alterations predominantly in granulocytes during neonatal development. Liver intravital microscopy from birth through adulthood captures real-time dynamics, showing a substantial presence of Ly6G + cells that persisted significantly up to 2 weeks of age. Using CyTOF, we characterized neonatal Ly6G + cells as neutrophils, confirmed by morphology and immunohistochemistry. Surprisingly, the embryonic liver hosts a distinct population of neutrophils established as early as the second gestational week, challenging conventional notions about their origin. Additionally, we observed that embryonic neutrophils occupy preferentially the extravascular space, indicating their early establishment within the liver. Hepatic neutrophils in embryos and neonates form unique cell clusters, persisting during the initial days of life, while reduced migratory capabilities in neonates are observed, potentially compensating with increased reactive oxygen species (ROS) release in response to stimuli. Finally, in vivo imaging of acute neutrophil behavior in a newborn mouse, subjected to focal liver necrosis, unveils that neonatal neutrophils exhibit a reduced migratory response. The study provides unprecedented insights into the intricate interplay of neutrophils within the liver, shedding light on their functional and dynamic characteristics during development.

In-vivo investigation of dimethoate toxicity on serum enzymes, target organs and intestinal tissues of albino rats

Dimethoate is a broad spectrum organophosphate insecticide used to control agricultural, industrial and domestic pests. Despite its benefits, toxicities in non-target organisms have been widely reported. This study investigated acute and sub-chronic toxicities of dimethoate in rats. The arithmetic method of Karbar and a modification of repeated 8-week oral toxicity were adopted for the determination of acute and sub-chronic toxicities of dimethoate, respectively. Symptoms of acute toxicity evaluated include muscular weakness, respiratory distress, convulsion and death. Animals that were used for the sub-chronic toxicity studies were divided into 4 groups of 5. Groups 2, 3 and 4 were fed with feeds containing 200, 500 and 800 mg/kg dimethoate respectively, while group 1 served as the control. The weight of the animals were determined weekly for 8 weeks, and thereafter sacrificed. Blood samples were collected for biochemical tests, and the liver, kidney, lung, intestine and heart were excised and processed for histopathological analysis. The calculated median lethal dose (LD50) was 176 mg/kg. Animals in all groups gained weight progressively. However, a dose-dependent significant rise in alanine transaminase and alkaline phosphatise, but not aspartate transaminase accompanied with significant focal necrosis in liver, eosinphilic casts in kidney and intestinal ulceration in group 3 and 4 in animals. In addition, dimethoate- induced inflammation was observed in the liver, kidney, lung and intestine tissues. The derangement of biochemical parameters and relevant histopathological alterations observed in rats exposed to dimethoate are suggestive of toxicity. Therefore necessary precautionary measures should be taking during handling and use.

First isolation and genomic characterization of avian reovirus from black swans (Cygnus atratus) in China

Identification and analysis of the avian reovirus from black swan. Isolation of the strain through the chorioallantoic membrane route of duck embryos, identified through transmission electron microscopy and RT-PCR based on the ARV S2 gene. The complete genome of the ARV strain was obtained using next-generation sequencing technology. The isolated strain of ARV was named CD200801 and was identified through transmission electron microscopy and RT-PCR based on the ARV S2 gene. Experimental infection with CD200801 resulted in the death of ducklings with serious spleen and liver focal necrosis. BLAST analysis of CD200801 sequences showed a 35.5 to 98.6% similarity to a novel duck reovirus that was isolated in recent years. Phylogenetic analysis revealed that CD200801 was closely related to ARV isolates YL, GX-Y7, and XT-18. We report the first avian reovirus infection in the black swan. This study provides important new insights into the evolutionary relationships among different ARV strains and highlights the need for continued surveillance and monitoring of these viruses in both domestic and wild bird flocks. These findings have significant implications for the development of effective strategies for disease prevention and control in the poultry industry.

Rebalancing liver-infiltrating CCR3+ and CD206+ monocytes improves diet-induced NAFLD

Melatonin has been reported to improve nonalcoholic fatty liver disease (NAFLD), and exploring the underlying mechanisms will be beneficial for better treatment of NAFLD. Choline-deficient high-fat diet (CDHFD)- and methionine/choline-deficient diet (MCD)-fed mice with melatonin intervention exhibit significantly decreased liver steatosis, lobular inflammation, and focal liver necrosis. Single-cell RNA sequencing reveals that melatonin selectively inhibits pro-inflammatory CCR3+ monocyte-derived macrophages (MoMFs) and upregulates anti-inflammatory CD206+ MoMFs in NAFLD mice. Liver-infiltrating CCR3+CD14+ MoMFs are also significantly increased in patients with NAFLD. Mechanistically, melatonin receptor-independent BTG2-ATF4 signaling plays a role in the regulation of CCR3+ MoMF endoplasmic reticulum stress, survival, and inflammation. In contrast, melatonin upregulates CD206+ MoMF survival and polarization via MT1/2 receptors. Melatonin stimulation also regulates human CCR3+ MoMF and CD206+ MoMF survival and inflammation invitro. Furthermore, CCR3 depletion antibody monotherapy inhibits liver inflammation and improves NAFLD in mice. Thus, therapies targeting CCR3+ MoMFs may have potential benefits in NAFLD treatment.

Non-clinical safety evaluation of salvianolic acid A: acute, 4-week intravenous toxicities and genotoxicity evaluations

BackgroundToxicological problem associated with herbal medicine is a significant public health problem. Hence, it is necessary to elaborate on the safety of herbal medicine. Salvianolic acid A (SAA) is a major active compound isolated from Danshen, a popular herbal drug and medicinal food plant in China. The aim of the present study was to explore the toxicological profile of SAA.MethodsThe acute toxicity studies were performed in mice and Beagle dogs with single administration with SAA. A 4-week subchronic toxicity was test in dogs. SAA was intravenously administered at doses of 20, 80 and 300 mg/kg. Clinical observation, laboratory testing and necropsy and histopathological examination were performed. The genotoxic potential of SAA was evaluated by 2 types of genotoxicity tests: a reverse mutation test in bacteria and bone marrow micronucleus test in mice.ResultsIn acute toxicities, the LD50 of SAA is 1161.2 mg/kg in mice. The minimum lethal dose (MLD) and maximal non-lethal dose (MNLD) of SAA were 682 mg/kg and 455 mg/kg in dogs, respectively. The approximate lethal dose range was 455–682 mg/kg. In the study of 4-week repeated-dose toxicity in dogs, focal necrosis in liver and renal tubular epithelial cell, the decrease in relative thymus weight, as well as abnormal changes in biochemical parameters, were observed in SAA 80 or 300 mg/kg group. The no observed adverse effect level (NOAEL) of SAA was 20 mg/kg. Thymus, liver and kidneys were the toxic targets. These toxic effects were transient and reversible. These results indicated that it should note examination of liver and kidney function during the administration of SAA in clinic. Furthermore, SAA had no mutagenic effect at any tested doses.ConclusionThese results provide new toxicological information of SAA for its clinical application and functional food consumption.

Pathology of Fowl Paratyphoid and Molecular Detection of Its Pathogen in Layer Chickens

The study was aimed to ascertain the pathology of fowl paratyphoid and molecular detection of its causal agent (Salmonella spp) in chickens. Pathological and swab samples were collected from layers in Gazipur district, Bangladesh. For observing the gross and microscopic lesions of different organs necropsy and histopathology were done, and to isolate and identify the Salmonella spp, different bacteriological tests and Polymerase Chain Reaction (PCR) were performed. Swabs from 150 chickens showed 66% of salmonellosis. Gram’s staining of isolated bacteria showed pink colored rod shaped bacilli. In biochemical tests, Salmonella fermented dextrose, maltose, xylose, arabinose, dulcitol, mannitol except lactose and sucrose. Investigation of gross lesions at necropsy revealed hemorrhage and congestion in intestine, liver, spleen and ovaries. Necrotic foci were found in liver and spleen, and button like ulceration in cecal tonsils as well. Microscopic lesions included hemorrhage and focal necrosis in liver and spleen. Congestion and infiltrations of inflammatory cells were observed in small intestine. Ovary was hemorrhagic and there was infiltration of heterophils. Biochemically positive and isolated Salmonella organisms were confirmed by PCR method using invA and IE1 primers. The final results showed that a total of 91.7% Salmonella suspected cultures were confirmed as Salmonella Enteritidis. Ann. Bangladesh Agric. (2020) 24(2) : 47-57

Effects of oral exposure to zinc oxide nanoparticles on the peripheral organs of C57BL/6J mice

To investigate the effects of oral exposure of zinc oxide nanoparticles on multiple peripheral organs of C57BL/6J mice. ;Methods: Twenty male C57BL/6J mice were randomly divided into control group and experimental group, with 10 mice in each group. The experimental group was treated with continuous gavage administration of zinc oxide nanoparticle solution at a dose of 20 mg/kg body weight for 60 days, and the control group was given the corresponding amount of normal saline; the mice were weighed once a week. After the end of the exposure, blood samples was collected from the eyeballs, and the levels of blood sugar and lipids, liver and kidney function, and inflammatory factors such as platelet activating factor (PAF), interleukin-6 (IL-6) and tumor septicemia (TNF-α) were detected. Then, tissues sections of the heart, liver, spleen, lung, kidney and small intestine were prepared and their morphological changes were observed after hematoxylin-eosin staining. ;Results: There was no significant difference in body weight between control group and the experimental group. Compared with control group, the serum levels of albumin (ALB), albumin/globulin ratio(A/G), alkaline phosphatase (ALP) activity, aspartate aminotransferase/alanine aminotransferase ratio(AST/ALT), uric acid (UA) and blood urea in the experimental group were increased significantly (P＜0.05 or P＜0.01). There was no significant change in serum inflammatory factors. Pathological examination showed myocardial turbidity, mild inflammatory lesions (focal or small necrosis) in liver, decreased pigmentation in spleen, mild or moderate interstitial inflammation in lungs, and no obvious pathological changes in the kidneys or small intestine. ;Conclusion: Sixty days of oral exposure to nanometer zinc oxide did not cause inflammation in the blood system of C57BL / 6J mice, but it could induce mild pathological changes in the heart, liver, spleen and lungs, and lead to abnormal liver and kidney function.

Repeated-dose 26-week oral toxicity study of ginsenoside compound K in Beagle dogs.

Ginsenoside compound K (CK), a product produced by the intestinal bacteria-mediated breakdown of ginsenoside, exhibits a wide array of pharmacological activities against diverse targets. However, few of preclinical safety evaluation of CK is reported. The present study therefore sought to assess the toxicity of oral CK in Beagle dogs over a 26-week period. All dogs received 4, 12, or 36 mg/kg oral CK doses for 26 weeks with regular monitoring, followed by a 4-week recovery period. Animals were monitored through measurements of temperature, weight, food intake, blood chemistry and hematological findings, electrocardiogram (ECG) measurements, urinalysis, gross necropsy and organ weight and tissue histopathology. Animals in the 36 mg/kg group exhibited an apparent reduction in body weight over the study period, in addition to the presence of focal liver necrosis and increased plasma enzyme levels (alanine aminotransferase, ALT; alkaline phosphatase, ALP) consistent with hepatotoxicity, although there was some evidence suggesting this toxicity was reversible. Animals in the 4 and 12 mg/kg groups did not exhibit any apparent toxicity for any measured parameters. These results thus indicate that the no observed adverse effect level (NOAEL) in dogs is 12 mg/kg.

Preclinical safety of ginsenoside compound K: Acute, and 26-week oral toxicity studies in mice and rats

Ginsenoside compound K (CK) is a hydrolysate of ginsenosides in the soil bacteria. This study evaluated the toxicity of CK as acute and the 26-week repeated-dose. The results of acute toxicity show that CK administered orally to rats and mice did not cause mortality or toxicity at the maximum dosage of 8 g/kg and 10 g/kg, respectively. In the toxicity study for 26-week, rats were administered with CK at doses of 13, 40, or 120 mg/kg, and were observed for 26 weeks and recovery periods of four weeks. Under the conditions, asthenia, hypoactivity, loss of fur and body weight reduction were transiently noticed in males of 120 mg/kg group. Hepatotoxicity and nephrotoxicity also were evident including the elevation of liver and kidney relative weight, along with focal liver necrosis as well as the increase in plasma enzymes (ALT and ALP) in male rats receiving CK (120 mg/kg), but this toxicity might be reversible. For 13 and 40 mg/kg CK groups, there was no significant variation in food habits, clinical signs, urine analysis, body weight, biochemical and hematological values, organ coefficient and histopathology examination. The NOAEL for male and female rats were observed to be 40 and 120 mg/kg, respectively.

Hepatoprotective and Antioxidant Activities of the Essential Oil from Maqian (Zanthoxylum myriacanthum var. pubescens) in Streptozotocin-induced Diabetic Mice

Background & objectives: Diabetes is a metabolic disorder and it can affect many organs and different types of antioxidant enzymes through increased production of reactive oxygen species (ROS). A few essential oils have been reported to have antioxidant and antidiabetic effects. The objective of our present study is to explore the anti-diabetic potential of Maqian essential oil (MQEO). Aim: The aim of this study was to evaluate the hepatoprotective and antioxidant effect of MQEO in streptozotocin (STZ)-induced diabetes in mice. Method: Diabetes was induced in male ICR mice with a single intraperitoneal injection of STZ (200 mg/kg body weight). MQEO was administered orally for 7 days. At the end of experiment liver was weighed and enzymatic and non-enzymatic oxidative stress parameters were measured, and part of liver was examined by hematoxylin/eosin staining. Results: MQEO treatment resulted in significantly decreased MDA level and increased antioxidant enzymes including superoxide dismutase, catalase, glutathione peroxidase and glutathione-Stransferase in STZ-diabetic mice. Histology examination showed severe pathology changes in diabetic mice including congestion of sinusoids and focal necrosis in liver and MQEO restored tissue architecture almost as in the normal control mice. Conclusion: MQEO has pronounced antioxidant effect and could reverse liver damages in STZ-induced diabetic mice. It could be useful for controlling diabetic complications.

Immune Response to Koi Herpesvirus (KHV) of Koi and Koi × Red Common Carp (Cyprinus carpio).

ABSTRACTKoi herpesvirus (KHV), also known as Cyprinid herpes virus 3 (Cyprinid 3) is lethal disease in common carp and koi (Cyprinus carpio). Two different groups (KK and RK) were infected KHV by intraperitoneal injection. Fish for gene expression analysis were sampled at 0 h, 12 h, 24 h, 48 h and 72 h post infection (p.i). The results showed that two immune related gene, Interferons (INFs) ɑβ and Interleukin (IL)-12 p35 induced a high response in RK. The IL-12 p35 cytokine and Toll-like receptor (TLR) 9 were significantly high expressed on 48 h post infection (p.i) in RK as compared to the KK. The histopatological examination reveals focal necrosis in liver and infiltrate of lymphocytes in spleen of KK as compared to the RK. In immunohistochemistry analysis, the KHV protein high expressed in the infected kidney cell and slenocyte of KK. Therefore, the expression of IL-12 p35, IFN ɑβ and TLR 9 may provide a potentially genes related with KHV resistance in Koi and red common carp × koi.

Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats.

Doxorubicin (DOX), a potent broad‑spectrum chemotherapeutic agent used for the treatment of several types of cancer, is largely limited due to its serious side effects on non‑target organs. Thus, the present study aimed to investigate whether berberine (Ber), an isoquinoline alkaloid, could reduce DOX‑induced acute hepatorenal toxicity in rats. Fifty rats were randomly divided into five groups: i)Control group, ii)DOX group, iii)DOX+Ber (5mg kg) group; iv)DOX+Ber (10mg kg), and v)DOX+Ber (20mg kg) group. In the tests, body weight, organ index, general condition and mortality were observed. In addition, the serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TCHO) and blood urea nitrogen (BUN) were determined to evaluate hepatorenal function. Hepatorenal toxicity was further assessed using hematoxylin and eosin stained sections. Furthermore, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) in rat serum or tissue homogenate were also assessed to determine the mechanisms of action. Results suggested that pretreatment with Ber ameliorated the DOX‑induced liver and kidney injury by lowering the serum ALT, AST, TCHO and BUN levels, and the damage observed histologically, such as hemorrhage and focal necrosis of liver and kidney tissues induced by DOX were also attenuated by Ber. Furthermore, Ber also exerted certain antioxidative properties through reversing the changes in the levels of MDA, SOD, GSH and MDA induced by DOX. These findings indicate that Ber has protective effects against DOX‑induced acute hepatorenal toxicity in rats. Combination of Ber with DOX is a novel strategy that has the potential for protecting against DOX‑induced hepatorenal toxicity in clinical practice.

Crizotinib-induced toxicity in an experimental rat model.

The aim of the present study was to evaluate the effect of crizotinib on visceral organs in an experimental rat model. Eighteen Wistar albino rats were divided into three groups: experimental toxicity was induced with crizotinib (10mg/kg) administered for 28 days (Group 1), 42 days (Group 2) orally by gavage. Control group received only distilled water. Rats in Group 1 and Group 2 were sacrificed after the collection of blood and tissue samples on the 28th and 42nd days, respectively. Subjects in Group 1 and Group 2 had abnormal histology mainly in lung and liver. There were intraalveolar hemorrhage in lungs; mild portal inflammation, perivenular focal and confluent necrosis in liver; inflammatory reaction in renal pelvis and periureteral areas, and focal pancreatitis in pancreas. This study is the first to evaluate the histopathological features of toxicity of crizotinib in a rat model.

Ebola viral encephalitis and myelitis

Ebola Virus Disease (EVD), formerly known as Ebola Haemorrhagic Fever, is a severe, often fatal illness in humans. To the best of our knowledge there is no link between Ebola and Encephalitis.Recent evidence suggests converging pathways through which viral infection, and its associated immune surveillance processes, may alter integrity of the BBB, and lead to inflammation, swelling of the brain parenchyma and associated neurological syndromes.Classical presentation is as a triad of fever, headache and altered mental state. There may be other findings either on examination or on imaging which, together with a travel history, may give clues as to the aetiology. It is important to note that in high- and middle-income countries the commonest cause of viral encephalitis is herpes simplex and Ebola.The organs of monkeys infected with Ebola haemorrhagic fever were examined by light and electron microscopy during the acute stage of disease. The virus caused focal coagulative necrosis in liver, spleen, kidney, lung and testis and widespread mild vascular damage. In brain there was intense congestion, with erythrocyte 'sludging', but no inflammatory reaction, significant injury to microvasculature in all organs. Virus replicated in endothelial cytoplasm causing focal necrosis, separation of tight junctions and detachment from basement membranes. These changes were associated with oedema and haemorrhage, contributing to hypovolaemic shock were not sufficiently extensive to account for severity of vascular collapse.Therefore, alongside with chest and abdominal pain, cough, conjunctivitis, jaundice, pancreatitis, lymphadenopathy, delirium, and coma, other complications after second week of infection include transverse myelitis and encepalitis. Ebola Virus Disease (EVD), formerly known as Ebola Haemorrhagic Fever, is a severe, often fatal illness in humans. To the best of our knowledge there is no link between Ebola and Encephalitis. Recent evidence suggests converging pathways through which viral infection, and its associated immune surveillance processes, may alter integrity of the BBB, and lead to inflammation, swelling of the brain parenchyma and associated neurological syndromes. Classical presentation is as a triad of fever, headache and altered mental state. There may be other findings either on examination or on imaging which, together with a travel history, may give clues as to the aetiology. It is important to note that in high- and middle-income countries the commonest cause of viral encephalitis is herpes simplex and Ebola. The organs of monkeys infected with Ebola haemorrhagic fever were examined by light and electron microscopy during the acute stage of disease. The virus caused focal coagulative necrosis in liver, spleen, kidney, lung and testis and widespread mild vascular damage. In brain there was intense congestion, with erythrocyte 'sludging', but no inflammatory reaction, significant injury to microvasculature in all organs. Virus replicated in endothelial cytoplasm causing focal necrosis, separation of tight junctions and detachment from basement membranes. These changes were associated with oedema and haemorrhage, contributing to hypovolaemic shock were not sufficiently extensive to account for severity of vascular collapse. Therefore, alongside with chest and abdominal pain, cough, conjunctivitis, jaundice, pancreatitis, lymphadenopathy, delirium, and coma, other complications after second week of infection include transverse myelitis and encepalitis.

NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity

The Beclin 1-Vps34 complex, the core component of the class III phosphatidylinositol-3 kinase (PI3K-III), binds Atg14L or UVRAG to control different steps of autophagy. However, the mechanism underlying the control of PI3K-III activity remains elusive. Here we report the identification of NRBF2 as a component in the specific PI3K-III complex and a modulator of PI3K-III activity. Through its MIT domain, NRBF2 binds Atg14L directly and enhances Atg14L-linked Vps34 kinase activity and autophagy induction. NRBF2 deficient cells exhibit enhanced vulnerability to ER stress that is reversed by re-introducing exogenous NRBF2. NRBF2 deficient mice develop focal liver necrosis and ductular reaction, accompanied by impaired Atg14L-linked Vps34 activity and autophagy, though the mice show no increased mortality. Our data reveals a key role for NRBF2 in the assembly of the specific Atg14L-Beclin 1-Vps34-Vps15 complex for autophagy induction. Thus, NRBF2 modulates autophagy via regulation of PI3K-III and prevents ER stress-mediated cytotoxicity and liver injury.

Rapidly progressing fatal reperfusion syndrome caused by acute critical ischemia of the lower limb

The most severe complication of ischemia-reperfusion injury following lower limb arterial surgery is reperfusion syndrome. Therefore, our aim was to describe the extent of muscle damage and the reperfusion syndrome-related remote organ lesions in detail, through a well-documented case of long-lasting infrarenal aorta thrombosis. After urgent revascularization, several clinical signs of multiple organ dysfunction were detectable, including the circulatory, urinary, respiratory, gastrointestinal, and hemostatic systems. Upon histological examination, intraoperative muscle biopsy showed severe muscle damage. Muscle fiber viability was assessed with a special nitroblue tetrazolium staining-based viability test developed by our team; the obtained results indicated significant degree of muscle damage before this was confirmed by conventional histological methods. Thorough postmortem examination confirmed the presence of remote organ damage. The pathological findings included acute tubular necrosis, myocardial and jejunal infarctions, ischemic pancreatitis, and diffuse alveolar damage with hyaline membrane formation in the lungs and focal centrilobular liver necrosis. By using special staining techniques, the presence of myoglobin and lipofuscin deposits was confirmed in the kidney samples. In this paper, we present a patient who developed all major complications following long-lasting arterial occlusion. We also introduce a novel method to assess the degree of ischemic injury, which may be suitable in the near future for the rapid detection of irreversible muscle injury. Therefore, the mortality of the disease might be reduced.

Clinical analyses of laparoscopic hepatectomy for liver neoplasms: a report of 21 cases

The clinical data were retrospectively analyzed for 21 cases of liver neoplasms undergoing laparoscopic hepatectomy from December 2007 to October 2012. Among 11 cases of borderline hepatocellular carcinoma (HCC) (1.0-9.0 cm), 6 of them were of micro hepatocellular carcinoma (MHCC) with a diameter ≤2 cm. There were 10 cases of borderline hepatic benign tumor, including liver hemangioma (n=7), hepatic adenoma (n=1), liver lymphoma (n=1) and liver focal necrosis (n=1). According to Couinaud's liver segmentation method, neoplasm was located on segment Ⅲ (n=13), segment Ⅳ (n=6), segment Ⅴ (n=1) and segment Ⅵ (n=1). Laparoscopic hepatectomy was successful in all patients. There was neither conversion into open approach nor postoperative complications of bile leakage, air embolism or perioperative mortality, etc. The mean operative duration was (120 ± 30) minutes, average hemorrhagic volume (165±79) ml and normal diet & ambulation at Day 1-2 post-operation. The average postoperative hospitalization stay was (16±10)days and 1-year survival rate 100%. The parameters of leucocyte, liver enzymes, albumin and bilirubin returned to normal at Week 1 post-operation. Once a reasonable surgical indication is selected, laparoscopic resection is both safe and effective for peripheral micro hepatocellular carcinoma. Key words: Liver neoplasms; Laparoscopy

Protective Effect of Petroselinum crispum(parsley)extract on histopathological changes in liver ,kidney and pancreas induced by Sodium Valproate- In male Rats

The present study was done to investigate the protective effect parsley extract against liver ,kidney ,pancreas damage induced by sodium valoproate in rats,The protective effect of alcoholic parsley extract against toxicity induced by sodium valproate (SVP) in male rats was studied. These experiment was carried out along 7 weeks, twenty four male rats divided into three equal groups. Group (1) was kept as normal control (given vehicle), while rats of group (2) were given orally SVP in a dose of 500 mg/kg /day. While group (3) protected by parsley extract dose of 200 mg/kg /day and receive orally SVP in a dose of 500 mg/kg /day for 7 weeks at end of experiment animal were scarified and tissue of liver ,kidney and pancreas were isolated for study histopathological changes . The histopathological changes of liver reveal mild degree of steatosis reflected by micro vacuoles of the cytoplasm , Loss of normal arraying of hepatocytes indicates mild degree of liver atrophy , central vein. Focal liver necrosis, the dead cells are replaced by leukocytic infiltration .The histopathological changes of kidney tissue treated with valproate reveal The proximal and the distal convoluted tubules show hydropic changes(small white vacules within the cytoplasma and The glomeruli show hypercellularity. More ever study reveal there is no histopathological changes could be detected in pancreas except there is interstitial edema in animal treated with valproic acid. Conclusion: Petroselinum crispum(parsley) exhibited significant anti-hepatotoxic activities and protective activity on kidney damage induced by valoproic acid .

Impairment of endoplasmic reticulum in liver as an early consequence of the systemic inflammatory response in rats

It is well known that systemic inflammatory response (SIR) often causes liver dysfunction. The aim of this study was to identify the intracellular compartment in the liver most susceptible to SIR. We analyzed morphology, ultrastructure, proteome, and expression of relevant genes in livers of rats subjected to endotoxic shock. Histological examination revealed that focal necrosis in liver was insignificant to explain liver dysfunction. Electron microscopy revealed no morphological changes in the mitochondrial structure and in the cytosol, but dilated endoplasmic reticulum (ER) cisterns were frequently observed. Apoptosis was found in white blood cells within liver tissue but not in hepatocytes. Mitochondrial, ER, and cytosolic fractions were subjected to proteome analysis by difference gel electrophoresis, and the protein spots with the highest degree of differential regulation were identified with mass spectrometry. The most pronounced proteome changes appeared in the ER, manifested as a remarkable downregulation of several proteins essential for ER functions, such as protein synthesis and transport, whereas the changes in mitochondrial and cytosolic fractions suggested a compensatory response. ER stress, as an underlying mechanism for ER impairment, was confirmed by analysis of upstream (splicing X-box-binding protein 1 mRNA) and downstream (e.g., 78-kDa glucose-regulated protein mRNA) markers, suggesting ongoing unresolved ER stress as a cause for ER dilation. Because ER is the intracellular compartment responsible for the major liver functions, our data suggest that inflammatory mediators induce unresolved ER stress, resulting in the biochemical, functional, and morphological impairment of ER that in turn causes liver dysfunction. The pathway activating ER stress in response to SIR is not known yet.

The African Green Monkey (Cercopithecus aethiops) as a non-human primate model for infections with Cyclospora Cayetanensis

Clinical epidemiology and pathogenesis of Cyclospora species was studied in 64 wild-trapped Cercopithecus aethiops at the Institute of Primate Research, Nairobi, Kenya. The monkeys were screened for Cyclospora parasites using conventional microscopy, examination of hot Safranin stained faecal smears, Cyclospora specific antibody responses and molecular characterization of DNA following nested Polymerase Chain Reaction (PCR) amplification. Efficacy of Trimethoprim-Sulphamethoxazole therapy for Cyclospora positive monkeys was evaluated. Experimental Cyclospora infections were established by oral inoculation. Oocyst shedding was used to confirm establishment and duration of infection. Gross and histopathological characteristics were described . The animals remained asymptomatic. Cyclospora parasites were identified in 41 (64%) of animals with infections mostly in male adults. Incubation period was 14-17 days, the duration of infection one to two months. A PCR product of 294 base pair was visualized, confirming Cyclospora species in the natural and experimental infections. Cyclospora specific antibody responses were recorded in positive monkeys. Response to treatment was evaluated by cessation Cyclospora oocyst shedding by D17 post-treatment and decreased Cyclospora specific antibody levels. Relapse infections occurred in 33% of the treated animals but responded to second TMP-SMX therapy. Pathological findings recorded were moderate haemorrhagic enteritis, parasites vacuoles in the enterocytes, mild lymph node enlargement, lymphocytic infiltrations, focal necrosis and granulomas in the liver. In conclusion, the study demonstrated that AGM may offer a suitable model for study of cyclosporiasis.