Study on the effect of processing methods on the total polyphenol, 2,3,5,4'-tetrahydroxystilben-2-O-ß-D-glucoside, and physcion contents in Fallopia multiflora Thunb. Haraldson root

Abstract This study investigated the changes in the ingredients in Fallopia multiflora Thunb. Haraldson (FMT) root after processing it with different methods such as soaking, stewing, and steaming or combined methods. The total polyphenol, 2,3,5,4'-tetrahydroxystilben-2-O-ß-D-glucoside (THSG), and physcion contents in FMT products after processing were determined using high-performance liquid chromatography (HPLC) and ultraviolet-visible (UV-VIS) methods. The results demonstrated that the processing method and time significantly affected the contents of polyphenol, THSG, and physcion. The physcion and total polyphenol content increased or decreased during processing depending upon the processing time, while the THSG content gradually decreased with an increase in the processing time. The content of physcion (a substance that can cause liver toxicity) was analysed, and the suitable conditions for processing of the FMT products were determined as initial soaking in rice swill for 24 h and subsequent stewing with black beans and water for 12 h

The Human Host Defense Peptide LL-37 Overexpressed in Lung Cell Lines by Methanolic Extract of Valeriana officinalis

Abstract The present study investigated the effects of valerian methanolic extract and valerenic acid on the expression of LL-37 gene and protein in A549 and MRC5 line cells. After preparing Valerian seeds, sowing them in March 2020, and harvesting the rhizome in October 2020, the extract was prepared from the valerian rhizome by maceration method. Valerian acid content was determined using high performance liquid chromatography (HPLC). Two cell lines (A549 and MRC-5) were used to study the effects of valerian extract, and the MTT test was used to evaluate cell viability. The expression of LL-37 mRNA and protein was assessed by Real-Time PCR and western blot, respectively. In vivo safety assessments and histopathological analysis were also conducted. Data was analyzed by Graphpad Prism 8 software. Valerian methanolic extract and valerenic acid upregulated the LL-37 mRNA and protein expression in both treated cell lines. Valerenic acid showed a greater effect on upregulating LL-37 expression than valerian methanolic extract. A549 cells were more sensitive to valerian methanolic extract compared to MRC5 cells, and its cell viability was reduced. Furthermore, liver and kidney-related safety assessments showed that valerian methanolic extract had no toxic effects. In general, it was concluded that the methanolic extract of valerian as well as the resulting valerenic acid as the most important component of the extract has the ability to upregulate LL-37expression. Therefore, methanolic extract of valerian and valerenic acid can be considered for improving the immune system.

Free interstitial levels of metformin in the liver of healthy and diabetic Wistar rats

Abstract In the present study, free interstitial levels reached by metformin in the liver were investigated in control and diabetic rats by microdialysis. Firstly, a bioanalytical method using an HPLC-UV system to determine the drug concentration in microdialysis samples was validated. The blood glucose levels and biochemical parameters were investigated in control and diabetic animals. Following that, both groups received a dose of 50 mg/kg of metformin iv bolus and the free interstitial levels reached in the liver were assessed by microdialysis. The method was validated according to FDA guidelines being suitable to quantify free concentrations of metformin in the liver of control and diabetics rats. Free exposure to metformin was similar in control and diabetic animals: AUC0-∞ 118.50 ± 40.18 vs 112.93 ± 50.25 µg.h/mL, respectively. The half-life in tissue was similar to that described in the literature for plasma. Hence diabetes induced by streptozotocin after administration of nicotinamide in our study did not damage the renal and hepatic function of the animals. The levels reached in the liver were 1.6 times higher than the free plasma concentrations, demonstrating higher liver penetration of metformin. This is the first investigation in liver interstitial concentration of metformin in control and diabetic rats

Protective effects of Baicalin injection on severe acute pancreatitis through regulating follistatin-like-1 signaling pathway by down-regulating miR-429 expression in mice

Abstract In China, Scutellaria is used for treating inflammatory-related diseases. Baicalin is the main active component of Scutellaria and has protective effects on acute pancreatitis. However, the mechanism of Baicalin is still unclear. In this study, the protective effects of baicalin on acute pancreatitis induced by taurocholate and its mechanism are investigated. In this study, mice were randomly divided into three groups: sham operation, model, and treatment groups. Acute pancreatitis in mice was induced by intraperitoneal injection of taurocholate (35 mg/kg). The treatment group was given baicalin (100 mg/kg) 2 h before acute pancreatitis induction. The mRNA expression levels of miR-429, nuclear factor kappa B65(NF-kB65), toll-like receptor 4(TLR4), TNF receptor associated factor6 (TRAF6), NF-kappa-B inhibitor(IkB), Follistatin-like 1 (FSTL1), and interleukin-1 receptor-associated kinase (IRAK) in the liver tissues 24 h after intraperitoneal injection were detected by RT-PCR. Then, the expression levels of NF-kB65, p-NF-κB65, TLR4, TRAF6, IkB, FSTL1, IRAK, p- IRAK, and p- IkB-а proteins were detected by Western blot. IL-6, TNF-α and IL-1 ß in plasma were measured by ELISA, and histopathological changes in the pancreases of the mice were observed. The results showed that after baicalin treatment, miR-429 expression in the pancreatic tissues and the expression levels of NF-kB65, TLR4, TRAF6, p-IkB-а, FSTL1, and p-IRAK decreased. Similarly, pancreatic myeloperoxidase (MPO) activity and the plasma levels of IL-6, TNF-а, IL-12, IL-1ß1, endotoxin, serum amylase, and lipase were reduced. Thus, the pancreatic injury induced by taurocholate was alleviated. The present study indicates that pretreatment with Baicalin can alleviate acute pancreatic injury induced by taurocholate in mice. The mechanism may be associated with the decreased miR-429 expression, reduced FSTL1 signaling pathway activity, TLR4 and TLR4/MyD88 signaling pathway inhibition, and reduced pancreatic inflammation. FSTL1 is the regulatory target for miR-429

Efficacy of an herbal compound in decreasing steatosis and transaminase activities in non-alcoholic fatty liver disease: A randomized clinical trial

Abstract Hepatoprotective effects of many herbal agents have been reported in animal studies and clinical trials. In this study, five hepatoprotective plants with potent antioxidant, anti-inflammatory, and hypolipidemic effects were chosen to prepare a polyherbal compound for managing NAFLD. Sixty patients with NAFLD were randomly divided into treatment and control groups (2:1 ratio). Both group were advised to take healthy diet and exercise. The treatment group also received herbal capsules containing 400 mg of the mixture of Anethum graveolens, Citrus aurantium, Cynara scolymus, Portulaca oleracea, and Silybum marianum (2 capsules, thrice daily, for two months). The liver ultrasound and biochemical markers including the serum lipids, liver enzymes, and glucose were evaluated before starting the study and at the end of the treatment. Thirty patients in the treatment group and sixteen patients in the control group completed the study. The herbal compound significantly decreased the serum level of alanine transaminase (ALT), aspartate transaminase (AST), and total cholesterol. Treatment with the herbal compound significantly improved the grade of the fatty liver, but no significant change was found in the control group. In conclusion, the formulated herbal compound appeared to be effective in biochemical improvement and decreasing the grade of the fatty liver in the patients with NAFLD.

Effects of low-level laser therapy on liver regeneration and laser parameters employed / Efeitos da laserterapia de baixa potência na regeneração hepática e parâmetros empregados de laser

Low-level laser therapy has several biological effects; one of them is tissue regeneration. Recent studies have been held on the application of laser therapy on the liver of rats after partial hepatectomy to promote liver regeneration. The aim of this article was to review the recent studies on the effects of low-level laser therapy on rat liver regeneration after partial hepatectomy and the laser parameters used in those studies. A review of recent relevant literature was performed in Pubmed, Scielo, Medline, and Bireme databases. Articles related to the application of low-level laser therapy on hepatic regeneration were included. Articles with hepatic regeneration in the presence of pathologies were not included. Nine studies were found matching the study criteria. In most studies, low-level laser therapy promoted liver regeneration after partial hepatectomy, without further damage to the remaining liver. Not all laser parameters required for the reproducibility of the study were described by all authors. The therapeutic use of low-level laser therapy in liver regeneration can be promising; however, since the liver is a vital organ, and the laser application is intraoperative, future studies are necessary. The parameters used must be properly described and standardized to allow the reproducibility of the study, in order to define a therapeutic window and thus, consider its clinical use. It is also essential to clarify the mechanisms by which laser promotes liver regeneration to guarantee its safety and therapeutic efficacy.

Laserterapia de baixa potência tem vários efeitos biológicos, sendo um deles a regeneração de tecido. Sua aplicação no fígado de ratos após hepatectomia parcial para promoção de regeneração hepática tem sido estudada recentemente. O objetivo deste artigo foi revisar os estudos recentes dos efeitos da laserterapia de baixa potência na regeneração de fígado de ratos após hepatectomia parcial de fígado e os parâmetros de laser empregados. Uma revisão da literatura relevante recente foi realizada nas bases de dados Pubmed, Scielo, Medline e Bireme. Artigos sobre a aplicação da laserterapia de baixa potência na regeneração de fígado foram incluídos. Artigos sobre regeneração hepática na presença de patologias foram excluídos. Nove estudos foram encontrados correspondendo aos critérios do estudo. Na maioria dos estudos, a laserterapia de baixa potência promoveu regeneração hepática após hepatectomia parcial, sem causar danos adicionais ao fígado remanescente. Não foram descritos todos os parâmetros necessários para reprodutibilidade dos estudos por todos os autores. O uso terapêutico da laserterapia de baixa potência na regeneração de fígado pode ser promissor, entretanto, como o fígado é um órgão vital e a aplicação do laser é intraoperativa, estudos futuros são necessários, assim como os parâmetros da aplicação de laser precisam ser descritos apropriadamente e padronizados, para permitir a reprodutibilidade do estudo, para que uma janela terapêutica possa ser definida e seu uso clínico possa ser considerado. Também é essencial esclarecer através de quais mecanismos o laser promove regeneração de fígado para garantir sua segurança e eficácia terapêutica.

Effect of long-term consumption of oxidized polyunsaturated fatty acids on atherosclerotic lesion in LDL receptor knockout mice / Efeito do consumo crônico de ácidos graxos poliinsaturados oxidados na aterosclerose em camundongos knockout para receptor de LDL

Polyunsaturated fatty acids (PUFA) are susceptible to enzymatic and non-enzymatic oxidation, leading to the production of secondary compounds that present different physiological effects. Among the PUFA, the products formed from Omega 6 (n-6 FA) and Omega 3 (n-3 FA) fatty acids oxidation can modulate inflammation, dyslipidemia and oxidative stress preventing or reducing the atherosclerosis progression. In fact, the effect of chronic intake of edible oils containing products of polyunsaturated fatty acids oxidation (POPs) on atherosclerosis is still controversial. In general POPs from n-6 FA have a more pro-inflammatory profile than POPs from n-3 FA. Thus, the objective of this study was to compare the chronic intake of partially oxidized n-6 FA and n-3 FA rich oils on atherosclerosis biomarkers. Initially, six edible oils containing a higher amount of n-6 and n-3 FA were submitted to oxidative conditions, simulating the steps of transport, storage and consume. It was observed that oxidative reaction started in all oils since the first step and at the moment of consumption, some oxidative chemical markers were out the legal range suggested by the Official Agencies. In addition, it was possible to identify the type of secondary product formed from each precursor oil, providing a better information for oils quality control. After this step, fish and soybean oils were chosen as n-3 FA and n-6 FA rich oils, respectively. Using LDLr(-/-) mice, the effect of three oxidative levels of soybean oil was evaluated after 24 weeks of supplementation. Animals fed with the oil with the highest level of oxidation (fried and reused oil) showed no body weight gain, suggesting that POPs from soybean oil at this level could promote a browning effect on white adipose tissue by increasing UCP-1 expression. This group also showed the highest concentration of lipoproteins in plasma. However, these metabolic differences did not accelerate atherosclerosis in the animals. Finally, the effect of POPs from n-3 FA and n-6 FA oxidation were compared also using LDLr(-/-) mice as model for experimental atherosclerosis. Some alterations observed after n-3 FA supplementation, such as the increase of liver weight, IL-6, SONPC, 8-HETE and 15-F2-Isop and the decrease of BAT and glucose, were reversed by their POPs. In addition, POPs from n-6 FA caused increased of LDL and 5-HETE. As observed in the previous study, these metabolic alterations were not enough to prevent or accelerate atherosclerosis, as measured by histological analysis of the lesion size in the aorta. These results suggest that although a significant amount of POPs are being consumed by diet, their metabolic effects did not influence atherosclerotic plaques in the animal model. However, besides lesion area in the aortas, new studies should also evaluate the plaques stability

Os ácidos graxos poliinsaturados (PUFA) são suscetíveis à oxidação enzimática e não enzimática, levando à produção de compostos secundários que apresentam diferentes efeitos fisiológicos. Entre os PUFA, os produtos formados a partir da oxidação dos ácidos graxos ômega 6 (n-6 FA) e ômega 3 (n-3 FA) podem modular a inflamação, dislipidemia e estresse oxidativo, impedindo ou reduzindo a progressão da aterosclerose. De fato, o efeito da ingestão crônica de óleos contendo produtos da oxidação de ácidos graxos poliinsaturados (POPs) na aterosclerose ainda é controverso. Em geral, os POPs dos n-6 FA têm um perfil mais pró-inflamatório do que os POPs dos n-3 FA. Assim, o objetivo deste estudo foi comparar a ingestão crônica de POPs provenientes de óleos ricos em n-6 FA e n-3 FA em biomarcadores de aterosclerose. Inicialmente, seis óleos ricos em n-6 FA e n-3 FA foram submetidos a condições oxidativas, simulando as etapas de transporte, armazenamento e consumo. Observou-se que a reação oxidativa iniciou-se em todos os óleos desde a primeira etapa e, no momento do consumo, alguns marcadores oxidativos estavam fora da faixa legal sugerida pelas agências reguladoras. Além disso, foi possível identificar o tipo de produto secundário formado a partir de cada óleo precursor, fornecendo melhores informações para o controle de qualidade dos óleos. Após esta etapa, os óleos de peixe e soja foram escolhidos como óleos ricos em n-3 FA e n-6 FA, respectivamente. Utilizando camundongos LDLr(-/-), o efeito de três níveis oxidativos de óleo de soja foi avaliado após 24 semanas de suplementação. Os animais alimentados com o óleo com maior nível de oxidação (óleo frito e de reuso) não apresentaram ganho de peso corporal, sugerindo que os POPs do óleo de soja nesse nível de oxidação pudessem promover um efeito de Browning no tecido adiposo branco, aumentando a expressão de UCP-1. Este grupo também mostrou a maior concentração de lipoproteínas no plasma. No entanto, essas diferenças metabólicas não aceleraram a aterosclerose nos animais. Finalmente, o efeito de POPs da oxidação de óleos ricos em n-3 FA e n-6 FA foi comparado também usando camundongos LDLr(-/-), como modelo para aterosclerose experimental. Algumas alterações observadas após a suplementação com óleo de peixe fresco, como aumento do peso hepático, IL-6, SONPC, 8-HETE e 15-F2-IsoP e diminuição da BAT e glicose, foram revertidas por seus POPs. Além disso, os POPs do óleo de soja causaram aumento de LDL e 5-HETE. Como observado no estudo anterior, essas alterações metabólicas não foram suficientes para prevenir ou acelerar a aterosclerose, medida pela análise histológica do tamanho da lesão na aorta. Esses resultados sugerem que, embora uma quantidade significativa de POPs esteja sendo consumida pela dieta, seus efeitos metabólicos não influenciaram as placas ateroscleróticas no modelo animal. Porém, além da área de lesão nas aortas, novos estudos também devem avaliar a estabilidade das placas

Palbociclib in breast cancer neoadjuvant setting

Cyclin-dependent kinase 4/6 inhibitors represent a major advance in breast cancer treatment, emerging as the standard of care of the initial treatment of hormone receptor-positive and HER2-negative metastatic breast cancer. Their activity in this subset of patients leads to interest in their use in the adjuvant and neoadjuvant settings. This case report presents a real-life case of cyclin-dependent kinase 4/6 inhibitors use in a patient initially considered to have stage IV luminal HER2-negative breast cancer with liver metastasis. The discrepancy of treatment response between the breast tumor and liver node led to a repetition of the liver biopsy, which revealed metastasis of a neuroendocrine tumor of unknown primary. The breast tumor showed a partial response, and the initial therapeutic strategy was then redefined for curative intent. While cyclin-dependent kinase 4/6 inhibitors are not yet approved for clinical practice in the neo / adjuvant treatment of hormone receptor-positive breast cancer, this case report portrays a successful example of its application in a neoadjuvant setting.

Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice

Up to date, the management of hepatotoxicity induced by a suicidal or unintentional overdose of acetaminophen (APAP) remains a therapeutic challenge. The present study aimed to elucidate the potential effect of sitagliptin, a DPP-4 inhibitor, to ameliorate the acute injurious effects of acetaminophen on the liver. APAP toxicity was induced in mice by an intraperitoneal injection of APAP (400 mg/kg). The effect of treatment with sitagliptin, initiated 5 days prior to APAP injection, was evaluated. Serum indices of hepatotoxicity, oxidative stress markers in liver tissues, serum IL-1ß, and TNF-α in addition to hepatic- NF-E2-related factor-2 (Nrf2) were determined. Our results showed that APAP induced marked hepatic injury as evidenced by an increase in serum levels of ALT and AST, in addition to the deterioration of histological grading. Oxidative stress markers, serum TNF-α, and IL-1ß were also elevated. Sitagliptin successfully ameliorated the histological changes induced by APAP, improving liver function tests and liver oxidant status accompanied with a marked increase in Nrf2 level in hepatic tissues. Thus, the hepatoprotective effects of sitagliptin in this animal model seem to involve Nrf2 modulation, coincidental with its anti-inflammatory and antioxidant effects

Costus root aqueous extract modulates rat liver toxicity, DNA damage, injury, proliferation alterations induced by plant growth regulator Ethephon

Ethephon (Ethrel®) is an ethylene-based plant growth regulator that used in agriculture and it has direct and indirect effects on human health, direct effect via its inhalation during usage in agriculture and indirect effect through the diet (Fruits and vegetables) that is sprayed with it. The current study aimed to examine the possible modifying effects of costus (Saussurea lappa) root aqueous extract against Ethephon induced liver toxicity, injury, DNA fragmentation and PCNA alterations in male rats. Fifty adult male rats were divided into 5 groups (1st, control; 2nd, Costus; 3rd, Ethephon; 4th, Post treated Ethephon with costus; 5th, self-healing Ethephon). Current results revealed that; a significant increase in aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), liver injury, DNA damage and PCNA expressions in Ethephon group when compared with control group. In contrast; a significant decrease in albumin and total proteins in Ethephon group when compared with control group. Treatment of rats with costus after Ethephon improved these alterations as compared with Ethephon self-healing. So, it could be concluded that costus root extract worth to be considered as a natural substance for ameliorating the hepatic toxicity induced by plant growth regulator Ethephon.

Antitumor efficacy of EDTA co-treatment with cisplatin in tumor-bearing mice

Ethylenediamine tetraacetic acid (EDTA) is used in various medical applications. The aim of this study is to investigate the antitumor efficacy of EDTA alone or with cisplatin (Cis). Fifty male albino mice were used to assess the median lethal dose (LD50) of EDTA via intraperitoneal (i.p) injection. To determine the antitumor activity, fifty female albino mice were divided into five groups as the following; Group 1 (Gp1) was negative control; (Gp2-5) inoculated i.p with 2×106 Ehrlich Ascites Carcinoma (EAC) cells/mouse. After one day, Gp3, Gp4 and Gp5 injected with Cis (2 mg/kg), EDTA (25 mg/kg) and Cis (2 mg/kg)/EDTA (25 mg/kg) for six days, respectively. At day 14, all groups were sacrificed to assess the tumor profile, liver enzymes (alanine transaminases and aspartate transaminases), kidney function (urea and creatinine) and electrolytes (Na+, K+ and Ca2+). The results showed that the i.p LD50 of EDTA was 250 mg/kg. Treatment with EDTA alone did not show any antitumor activity and did not interfere with the antitumor efficacy of Cis. Biochemical findings revealed that EDTA had mild toxicity on liver and kidneys functions. In summary, EDTA had no antitumor effect and did not alter the Cis efficacy.

Agenesia do lobo direito hepático: um achado incomum nos exames de diagnóstico por imagem / Agenesis of the right hepatic lobe: an unusual finding in diagnostic imaging tests

Hepatic lobar agenesis is an uncommon condition observed in 1/19,000 autopsies and may be rarer in the right lobe, with about 40 cases reported in the literature. Its diagnosis is based on the non-iden-tification of the hepatic duct, the corresponding portal and hepatic veins. We describe a case of right hepatic lobe agenesis as found in abdominal imaging in a 63-year-old woman with chronic diffuse abdominal discomfort and laboratory findings of a slight elevation of liver enzymes (AU)

Leiomiosarcoma intratesticular primario diagnosticado por biopsia hepática percutánea ecodirigida / Intratesticular Leiomyosarcoma Diagnosed by Percutaneous Liver Biopsy

Se presenta el caso clínico de un varón de 80 años diagnosticado de leiomiosarcoma testicular primario, a raíz de alteraciones del perfil hepático en analítica sanguínea y lesiones ocupantes de espacio (LOE) hepatoesplénicas en ecografía abdominal. En primer lugar, se realizó punción de lesión hepática y posteriormente orquiectomía radical, revelando concordancia histológica, compatible con leiomiosarcoma intratesticular. Presentamos el caso clínico debido a la rareza de ese tipo de tumores, sobre todo en estadio III, y su peculiar diagnóstico, tras la detección de alteración hepática tanto analítica como ecográfica

We present a case of an 80-year-old male diagnosed with primary testicular leiomyosarcoma due to the detection of hepatic profile analytical alterations and hepatosplenic space-occupying lesions in abdominal ultrasound. Puncture of hepatic lesion was performed first and radical orchiectomy later, revealing histological concordance, compatible with intratesticular leiomyosarcoma. We present the case due to the uncommon of this type of tumors, especially in stage III and its peculiar diagnosis, secondary of hepatic alteration, both analytic and ultrasound.

Influência da insulina sobre vias de sinalização envolvidas na peritonite provocada por inoculação de staphylococcus aureus em animais sadios e diabéticos / Influence of insulin on signaling pathways involved in peritonitis caused by inoculation of staphylococcus aureus in healthy and diabetic animals

Dentre tantas complicações do diabetes mellitus (DM), a infecção por bactérias comuns da microbiota superficial da pele como, por exemplo, a bactéria Gram-positiva Staphylococcus aureus, causadora de infecções como a peritonite, com altos índices de hospitalização e morte. A hipótese deste trabalho é a que o efeito da insulina na ativação das vias de sinalização MAPK, PKC e PI3K em peritonite induzida por S. aureus em animais diabéticos e não diabéticos possa regular a produção de citocinas. Foram utilizadas amostras de fígado, rim, linfonodos peritoniais e baço de animais oriundos de estudo anterior (Projeto FCF/USP-375), no qual animais diabéticos (aloxana, 42 mg/kg, i.v., 10 dias) e não-diabéticos com peritonite decorrente da infecção por S. aureus receberam uma dose de 4 UI e 1 UI de insulina NPH, respectivamente, por via subcutânea, 2 horas antes da infecção com S. aureus, e outras 3 doses de 2 UI e 0,5 UI às 17h00', respectivamente. A glicemia foi determinada no dia anterior, 10 dias após a injeção de aloxana e após os tratamentos com insulina. Em amostras de fígado, rim, linfonodo e baço dos animais supra citados foram avaliados a dosagem de citocinas (IL-1ß, IL-4, IL-10, TNF-α, CINC-1, CINC-2 e CINC-3) por ensaios de enzima-imunoensaio (ELISA); em homogenato de fígado foram avaliadas a expressão das moléculas das vias MAPK (fosfo P-38, fosfo ERK p42/44), PKC (fosfo PKC-α, fosfo PKC-δ) e PI3K (fosfo-AKT) pelo método de Western Blotting. Na avaliação do fígado, a insulina foi capaz de aumentar a concentração das citocinas IL-4 e TNF-α que apresentavam-se diminuídas em animais não diabéticos, em relação aos animais não diabéticos e não infectados, mas nos animais diabéticos, na infecção pela cepa N315, a insulina diminuiu a concentração de IL-4, que não estava alterada pela infecção, e não foi capaz de aumentar a concentração de IL-1ß que estava diminuída na infecção, em relação aos animais diabéticos e não infectados. Em linfonodos peritoniais de animais não diabéticos infectados pela cepa N315, a insulina diminuiu a produção de IL-1ß e IL-10, que não estavam alteradas na infecção, e diminuiu a concentração de IL-4, que estava aumentada na infecção, em relação aos animais não diabéticos e não infectados; em animais diabéticos, a insulina diminuiu a produção das citocinas IL-1ß e CINC-1, que estavam aumentadas, e aumentou a concentração de IL-10, que estava diminuída na infecção com a cepa N315, mas baixou a concentração de IL-4, em relação aos animais infectados, e na infecção pela cepa ATCC, a insulina aumentou a produção de IL-1ß, CINC-1 e CINC-3 dos animais tratados, em relação aos infectados e não tratados. Em baço, a insulina diminuiu a produção de IL-10 na infecção pela cepa ATCC tanto em animais não diabéticos quanto em animais diabéticos e, nesse último grupo, também aumentou a produção de CINC-3 em relação aos animais diabéticos não infectados; na infecção com a cepa N315, a insulina não aumentou a concentração de IL-1ß e TNF-α, que estavam diminuídas na infecção. Em rim, não houveram alterações significativas na produção de citocinas na infecção com nenhuma das cepas estudadas, nem para os grupos diabéticos, nem para os não diabéticos. Verificou-se que os animais diabéticos apresentam maior alteração tanto nas vias de sinalização estudadas quando na produção de citocinas pró-inflamatórias, quando comparados aos animais não diabéticos, na infecção por ambas as cepas de S. aureus estudadas. Assim, os resultados obtidos sugerem que o tratamento com insulina possa modular parcialmente a produção das citocinas IL-1ß, TNF-α e IL-10 no fígado e nos linfonodos peritoniais dos animais infectados principalmente pela cepa N315 de S.aureus, modulando parcialmente a expressão das moléculas da via de sinalização (MAPK e PKC), envolvidas na produção dessas citocinas

Among so many complications of diabetes mellitus (DM), infection by common bacteria of the superficial microbiota of the skin, for example, a gram-positive bacteria Staphylococcus aureus, causing infections like peritonitis, with high rates of hospitalization and death. The hypothesis of this study is that the effect of insulin on the activation of MAPK, PKC and PI3K signaling pathways in peritonitis induced by S. aureus in diabetic and non-diabetic animals may regulate the production of proinflammatory cytokines. Liver, kidney, peritonial lymph nodes and spleen samples of animals from the previous study (FCF / USP-375 Project) were used in this project; diabetic animals (alloxan, 42 mg / kg, iv, 10 days) and non-diabetic animals with peritonitis due to S. aureus infection received one dose of 4 IU and 1 IU of NPH insulin, respectively, subcutaneously, 2 hours before infection with S. aureus, and another 3 doses of 2 IU and 0.5 IU at 5:00 p.m., respectively. Blood glucose was determined the day before, 10 days after alloxan injection and after insulin treatments. In the liver, kidney, lymph node and spleen samples of the above-mentioned animals the cytokines (IL-1ß, IL-4, IL-10, TNF-α, CINC- 2 and CINC-3) by enzyme-immunoassay (ELISA) assays; we avaliated, by Western Blotting, the signaling pathways MAPK (phospho-P-38, phospho ERK p42 / 44), PKC (phospho PKC-α and phospho PKC-δ) and PI3K (phospho AKT) in liver, insulin was able to increase the concentration of cytokines IL-4 and TNF-α that were decreased in non-diabetic animals, in relation to non-diabetic and non-infected animals, but in diabetic animals, in strain N315, insulin decreased the concentration of IL-4, which was not altered by the infection, and was not able to increase the concentration of IL-1ß that was decreased in infection, relative to diabetic and uninfected animals. In peritonial lymph nodes from non-diabetic animals infected with the N315 strain, insulin decreased the production of IL-1ß and IL-10, which were not altered in the infection, and decreased the concentration of IL-4, which was increased in infection, in relation to non-diabetic and non-infected animals; in diabetic animals, insulin decreased IL-1ß and CINC-1 which were increased, and increased the concentration of IL-10, which was decreased in infection with strain N315, but decreased the concentration of IL-4 in Infected animals, and in infection by the ATCC strain, insulin increased the production of IL-1ß, CINC-1 and CINC-3 of treated animals over infected and untreated animals. In spleen, insulin decreased IL-10 production on infection by the ATCC strain in both non-diabetic and diabetic animals and, in this last group, also increased the production of CINC-3 in relation to uninfected diabetic animals; in infection with the N315 strain, insulin did not increased the concentration of IL-1ß and TNF-α, which were decreased in infection. In kidney, there were no significant changes in cytokine production in infection with any of the strains studied, neither for diabetic groups nor for non-diabetics. It was verified that diabetic animals present a greater alteration both in the signaling pathways studied and in the production of pro-inflammatory cytokines, when compared to non-diabetic animals, in the infection by both strains of S. aureus studied. Thus, the results suggest that insulin treatment may partially modulate the production of IL-1ß, TNF-α and IL-10 cytokines in the liver and in the peritonial lymph nodes of animals infected mainly with S. aureus strain N315, since they partially modulating the expression of signaling pathway molecules (MAPK and PKC), involved in the production of these cytokines

Agenesia del lóbulo hepático derecho asociado a agenesia vesicular / Agenesis of the right hepatic lobe associated with gallbladder agenesis

Background: Anatomical abnormalities of the liver are rare and their association with gallbladder agenesis are even more uncommon. Case report: We report a 63 years old man complaining of jaundice, without pain or fever. A magnetic resonance imaging showed a right hepatic lobe agenesis associated with gallbladder agenesis. Jaundice subsided spontaneously.

Introducción: Las anomalías anatómicas del hígado son raras, la asociación a una agenesia vesicular es más infrecuente aún, siendo su diagnóstico generalmente un hallazgo. Caso clínico: Presentamos el caso de un paciente masculino de 63 años que consulta por ictericia, sin dolor ni fiebre, al cual se le realiza diagnóstico por imagen con resonancia magnética de agenesia de lóbulo hepático derecho asociado a agenesia vesicular. Dado que el paciente no tiene litiasis biliar, se decide tratamiento médico.

Experiencia de diez años en resecciones hepáticas / Ten years experience in hepatic resections

Revisamos experiencia reciente y resultados obtenidos con resecciones hepáticas mayores en pacientes referidos a nuestra institución. Revisión retrospectiva de historias clínicas de pacientes entre agosto de 1998 y agosto de 2008, con el objetivo de precisar el tipo de cirugía efectuada, indicaciones principales, complicaciones y morbimortalidad operatoria. 22 pacientes cuyas historias estuvieron disponibles para revisión. La principal indicación de cirugía fueron neoplasias malignas 86,4% de los casos, las metástasis de carcinoma colorrectal (7) la primera indicación seguida de hepatocarcinoma (4). Otras indicaciones incluyeron: colangiocarcinomas perifericos (2), metástasis de tumores neuroendocrinos (2), diversas lesiones benignas (3) otros tumores (4). La hepatectomía derecha y segmentectomías anatómicas fueron los más frecuentes con un 27,3 % cada uno, seguidos de segmentectomía lateral izquierda (II y III) en 19%. El tiempo operatorio promedio fue 270,4 min (rango: 180-560 min). El promedio de estancia hospitalaria fue 7,7 días (rango:4-30). El 8% de nuestros pacientes no requirió estancia posoperatoria inmediata en UTI. La tasa de complicaciones fue 44,5% siendo el derrame pleural reactivo y el sangrado posoperatorio más frecuentes. La tasa de reintervención fue 18,2%. La mortalidad global fue 9% (2/22), y la inherente al procedimiento quirúrgico 4,5% (1/22). Las resecciones hepáticas mayores son un procedimiento relevante en el armamento del cirujano oncólogo dedicado al tratamiento de neoplasias digestivas, la morbimortalidad operatoria en nuestra institución es similar a otros centros de mayor volumen a nivel internacional.

Review the recent experience and results of major hepatic resections of patients treated at our institution. Retrospective review of clinical records patients submitted to major hepatic resection inten years, between August 1998 to August 2008, with descriptive statistics of type of surgery, indications, complications and surgical related morbimortality. Twenty two patients with complete clinical records for review were included. The main indication for surgery were malignant neoplasms in 86,4% of the cases,being colorectal liver metastasis (7) the first one followed by hepatocarcinomas (4). Other indications included:The periferic colanghiocarcinomas (2), metastasis from neuroendocrine tumors (2), varied beningn lesions (3)and other tumors (4). Right hepatectomy and anatomical segmentectomies were the most frequent procedures 27.3% each, followed by left lateral segmentectomy (II - III) in19% of the cases. Medium operative time was 270.4 min (range: 180-560 min). Mean hospital stay was 7.7 days (range: 4-30). 8% of the patients did not required post operative ICU care. Complications rate was 44.5% being reactive pleural effusion and postoperative bleedingthe most frecuent ones. Reintervention rate was 18.2%, global mortality 9% (2/22), and surgical related mortality was 4.5% (1/22). Major hepatic resections are a relevant procedure in the armament of surgical oncologists dedicated to treatment of digestive neoplasms, the number of such procedures done at public institutions are limited. Operative morbimortality in our institution is similar to other major volume centers.

A study on the anomalies of liver in the south Indian cadavers / Estudio sobre las anomalías del hígado en cadáveres del sur de India

Liver is the largest gland in the body and rarely shows variations in its lobes and fissures. We studied 55 Formalin-fixed livers for occurrence of abnormal shape, lobes, fissures and position of gall bladder. In 60 percent of cases the liver was normal. 40 percent livers showed one or the other variations. Additional lobes were found in 9.09 percent of cases. Additional fissure was found in 1.81 percent of cases. Presence of dumbbell shaped caudate lobe and presence of large papillary process was noted in 1.81 percent cases each. In 1.81 percent cases the fissure for ligamentum teres was absent or situated on the anterior surface of the liver. In 1.81 percent of cases each the liver was either extremely long or extremely flat. In 18.18 percent of the cases, the gall bladder was short and its fundus did not project beyond the inferior border of the liver. These findings may be useful for surgeons and radiologists.

El hígado es la glándula más grande del cuerpo y rara vez muestra variaciones en sus lóbulos y fisuras. Se estudiaron 55 hígados fijados en formalina para observar variaciones de su forma, lóbulos, fisuras y posición de la vesícula biliar. En el 60 por ciento de los casos, el hígado tuvo una forma normal. El 40 por ciento restante mostró alguna variante. Se encontraron lóbulos adicionales en el 9,09 por ciento de los casos. Una fisura adicional se encontró en 1,81 por ciento de los casos. La presencia de un lóbulo caudado en forma de mancuerna o reloj de arena, y la presencia de un gran proceso papilar se observó en el 1,81 por ciento de los casos, respectivamente. En 1,81 por ciento de los casos la fisura de ligamento redondo estaba ausente o situada en la superficie anterior del hígado. En 1,81 por ciento de los casos el hígado era muy largo o plana, respectivamente. En el 18,18 por ciento de los casos, la vesícula biliar fue corta y su fondo no se proyectó más allá del margen inferior del hígado. Estos resultados pueden ser útiles para cirujanos y radiólogos.

Serum γ - glutamyltransferase activity as an indicator of chronic liver injury in cattle with no clinical signs / γ - glutamiltransferase como indicador de lesão hepática crônica em bovinos sem sinais clínicos

This study aimed to determine the power of the serum aspartate aminotransferase (AST) and gamma-glutamyltransferasase (GGT) activities and of the albumin and cholesterol dosages for detecting hepatic histopathological injuries. A total of 220 healthy male Nelore cattle that had been extensively bred were evaluated. Blood and liver samples were collected on the day of slaughter for biochemical and histopathological tests. The results showed that the sensitivity to AST, GGT, albumin, and cholesterol tests were respectively 22.4%, 22.4%, 36%, and 37.2%.

Determinou-se a capacidade da dosagem das atividades séricas da aspartato aminotransferase (AST) e gama-glutamiltransferase (GGT) e das dosagens de albumina e de colesterol para a detecção de lesões histopatológicas hepáticas. Foram avaliados 220 bovinos, machos da raça Nelore, criados de forma extensiva. Amostras de sangue e de fígado foram coletadas para a realização dos testes histopatológicos e bioquímicos no dia do abate. Os resultados mostraram que a sensibilidade dos testes de AST, GGT, albumina e colesterol foram, respectivamente, de 22,4%, 22,4%, 36%, e 37,2%. A especificidade dos testes AST, GGT, albumina e colesterol foram, respectivamente, de 78,8%, 90,4%, 75,6% e 68,3%.

Liver Function Tests in Type 2 Diabetes Mellitus Patients with and without Oral Hypoglycemic Agents and Statin Intake.

Background: Type 2 diabetes (T2DM) is often associated with liver function abnormalities, covering the entire spectrum from asymptomatic transamnitis to cirrhosis. The oral drugs used in diabetes are also associated with hepatic insult. Aims: Here we have tried to assess the prevalence the liver function test abnormality in type 2 diabetes mellitus patients with special reference to intake of oral hypoglycemic agents (OHA) and statins. Methods: We selected 101 patients of Type 2 Diabetes mellitus (T2DM). Among those diabetic patients 50 were on oral hypoglycemic drugs (OHA) and statins for at least last 6 months. Another 51 age and sex matched patients were diabetic but not on these drugs. The patients were screened for any existing liver disease by biochemical tests. Results and analysis: Our results showed that the prevalence of elevated liver enzymes and bilirubin is more in Diabetic patient than normal values but the oral hypoglycemic drugs and statins had no added effect. Altogether 70 patients (69.3%) had at least one liver function test abnormality. In our study, 4.95% of the patients had elevated bilirubin (>2.5 mg/dL). 24.75% of the study patients had ALT levels above normal (40 U/L) although high values (>100 U/L) were present only in 5 (4.95%). High AST levels (>40) was found in 34.65% cases. Mean alkaline phosphatase levels in 2 groups were similar (213.96 ± 46.2 vs. 222.75 ± 42.52 U/ L). Serum proteins, INR and alkaline phosphatase did not also show any association with drug intake in our study. Conclusion: Thus screening for liver function abnormalities can be a useful test in diabetic population to prevent future complications.