Liver Albumin Research Articles

Improved liver function in patients with cirrhosis due to chronic hepatitis C virus who achieve sustained virologic response is not accompanied by increased liver volume.

BackgroundSerum albumin level improves in patients with chronic hepatitis C virus (HCV) infection who achieve sustained virologic response (SVR) with antiviral therapy. However, it remains controversial whether liver volume increases along with SVR.MethodsPatients with chronic HCV infection with a history of hepatocellular carcinoma (HCC) who achieved SVR with anti-HCV treatment from March 2003 to November 2017 were enrolled. Patients were followed up with periodic computed tomography (CT) scans to detect HCC recurrence. Patients who underwent treatment for HCC recurrence within 1 year after initiation of anti-HCV treatment were excluded. Laboratory data, including alanine aminotransferase (ALT) level, serum albumin level, and platelet count, were collected at baseline and timepoints after treatment initiation. Liver volume was evaluated at baseline and 24 and 48 weeks after treatment initiation using a CT volume analyzer. A linear mixed-effects model was applied to analyze the chronologic change in liver volume. The correlations between changes in ALT level, albumin level, and liver volume were also evaluated.ResultsOf 108 enrolled patients, 78 had cirrhosis. Serum albumin level continued to increase through 48 weeks after treatment initiation. A significant increase in liver volume was observed only in patients without cirrhosis (P = 0.005). There was a significant correlation between ALT level decrease and albumin level increase (P = 0.018).ConclusionsImproved liver albumin production with SVR was contributed by improved liver cell function rather than increased liver volume in patients with cirrhosis.

Albumin as prognostic value in hospitalised patients with femur neck fracture

Post-surgical state there might be a low formation of the albumin in liver or high degradation of the albumin. In either of the ways the serum albumin will be lowered. Stress and strain is also known to cause hypoalbuminemia i.e low serum level of albumin. Since albumin is a protein it has to be transcribed rom the genes and studies have shown that TNF - alpha supresses this transcription process.

Protective Role of Rockect Seed (Eruca sativa) Extract against Monosodium Glutamate-induced Hepato-renal Toxicity in Male Rats

Background and Objective: Monosodium glutamate (MSG) is identified as an Accent that is used in the food industry as a flavour enhancer with an umami taste that intensifies the meaty, savoury flavour of food. The present study aimed at evaluating the protective and ameliorative role of rocket seeds extract against monosodium glutamate-induced hepatic renal toxicity and oxidative stress in the male rat.
 Materials and Methods: A total of 60 male adult albino rats were equally divided into six groups (G1, Control; G2, rocket seeds (RS); G3, ACCENT or MSG; G4, Co- treated (RS+MSG); G5, Post- treated (MSG+RS); G6, Self-treated MSG). 
 Results: Current results revealed that; a significant increase in serum ALT, AST, ALP, AFP, Urea, Creatinine, potassium ions, chloride ions, cholesterol, triglyceride, HDL, and LDL levels in MSG as compared to control and RS groups. In contrast; a significant decrease in serum albumin, total proteins, catalase, GSH and SOD in liver and kidney homogenates in MSG as compared to control and RS groups. Co- or post-treatment of MSG with rocket seeds improved this change in liver and kidney functions, with best results for co-treatment than post and self-treatment.
 Conclusion: These findings suggested that the misuse of monosodium glutamate may contribute to continuous hepatic and renal damage. This shows that the desired dose of monosodium glutamate can safely be used with grapes seed in improving hepatic and renal damage in monosodium glutamate in young rats.

Serum Albumin Levels of Oral Candidiasis Immunosuppressed Rats Treated With Hyperbaric Oxygen

Objective: To investigate serum albumin levels in oral candidiasis immunosuppressed rats treated with hyperbaric oxygen. One of the predisposing factors for oral candidiasis was the use of immunosuppressive drugs continuously. It can also affect the work of the liver because it’s one of the organs responsible for drug metabolism. Hyperbaric oxygen therapy was used not only to suppressing fungal infections, but also to improve liver function by evaluating the serum albumin levels. Methods: This study used a post-test only control group design. Fifteen Wistar rats were divided into 3 groups(n=5/3): G1 (healthy group), G2 (oral candidiasis immunosuppressed rats group without hyperbaric oxygen therapy), and G3 (oral candidiasis immunosuppressed rats group with hyperbaric oxygen therapy). G2 and G3 groups were immunosuppressed by giving dexamethasone 0,5mg/day/rat orally for 14 days, added with tetracycline 1 mg/day/rat. Hyperbaric oxygen therapy was given to the G3 group in 5 days. Blood serum of rats in all groups was taken to calculate albumin levels. Results: The average value of albumin levels in G2 group showed a decrease compared to the G1 group, while G3 showed the highest level. One way Anova test showed a significant difference among groups (p<0,05). To compare the difference between each group we used LSD test and showed a significant difference (p<0,05) between G1 compared to G2, G1 compared to G3, and G2 compared to G3. Conclusion: Liver albumin levels of oral candidiasis immunosuppressed rats treated with hyperbaric oxygen therapy showed higher levels than those without therapy.

Combination of Caffeine and Liver Albumin Plus Protects against Smoking-Induced Liver Injury in Rats

Background: A number of studies have revealed the hepatoprotective effect of coffee and tea. However, the role of caffeine on smoking-induced liver injury is not well elucidated. Liver Albumin Plus (LAP) is a liver supplement given in different liver diseases; to our knowledge, its role in smoking-induced liver injury is not clear. Objectives: This study aimed to find out the protective effect of caffeine and LAP alone and in combination in attenuation of smoking-induced liver injury. Methods: Thirty male albino rats were divided into a control group and a smoking group; the smoking group was then subdivided into a smoking group, a smoking + caffeine group, a smoking + LAP group, and a smoking + caffeine + LAP group. At the end of the experimental study, blood samples were collected for assessment of liver enzymes, alpha-fetoprotein (AFP), and interleukin 6, and livers were excised. Biochemical analysis of hydrogen peroxide (H₂O₂), superoxide dismutase (SOD), and hypoxia-inducible factor (HIF) as well as histological examination were done. Results: The results showed that smoking elevated liver enzymes, AFP, H₂O₂, and HIF and decreased SOD; histologically, deterioration of the liver was observed. On administration of caffeine, significant (p < 0.05) improvement in all measured parameters and preserved liver histological structure were observed, while intake of LAP alone showed some improvement. In combination, all liver parameters were improved and histological structure was preserved in contrast to each drug alone. Conclusion: It is better to give a combination of caffeine and LAP with cigarettes smoking to attenuate smoking-induced liver injury.

Significance of the preoperative regional maximal removal rate of technetium-99m-galactosyl human serum albumin in the future remnant liver: a sequential study of regional maximal removal rate of technetium-99m-galactosyl human serum albumin in the whole liver.

The relationship between posthepatectomy complications and liver functional parameters was preliminary reported in a pilot study. The present study sequentially evaluated the clinical significance of maximal removal rate of technetium-99m-galactosyl human serum albumin (GSARmax) in the future remnant liver (rGSARmax) in patients to predict posthepatectomy complications. Between 2010 and August 2017, GSARmax, rGSARmax, their difference (Dif), and the rGSARmax to GSARmax ratio were examined in 247 additional patients who underwent hepatectomy for liver and biliary diseases. Hepatectomy-related postoperative complications (i.e. long-term ascites, intra-abdominal infection, and hepatic failure) occurred in 73 (29.6%) patients. The median and mean preoperative GSARmax values were 0.477 and 0.498±0.166 mg/min, respectively; rGSARmax values were 0.341 and 0.366±0.145 mg/min, respectively; Dif values were 0.105 and 0.132±0.111 mg/min, respectively; and the rGSARmax to GSARmax ratio values were 0.774 and 0.746±0.177, respectively. Among these, the GSARmax and rGSARmax values were significantly correlated with the liver functional parameters ICGR15, LHL15, HH15, prothrombin activity, serum hyaluronic acid level, and platelet count (all P<0.01). The rGSARmax values were significantly lower in patients with long-term ascites (P<0.05), and the predictive cutoff values of rGSARmax were 0.290 mg/min; however, the multivariate logistic regression analysis showed that rGSARmax was not independently related to long-term ascites. When accompanied by other functional liver reserve parameters, rGSARmax seemed to be an alternative liver functional parameter related to ascites.

A study of Serum Albumin level and it’s association in cure in chronically ill patients

Background: In cases of a pathological state there might be a low formation of the albumin in liver or high degradation of the albumin. In either of the ways the serum albumin will be lowered. Stress and strain is also known to cause hypoalbuminemia i.e low serum level of albumin. Since albumin is a protein it has to be transcribed rom the genes and studies have shown that TNF - alpha supresses this transcription process. The TNF – alpha is known to increase in any inflammation and thus forms a cascade. In case of hospitalised patients the stress and strain in pre surgical patients and chronically hospitalised patients the serum albumin levels are known to be less than normal. In chronically hospitalised patients the nutritional cause can also be taken into consideration for lower serum albumin levels. Early detection of these low levels of serum albumin levels helps the the physicians to intervene and thus cut off the progression of the disease. A sincere effort has been made in this study to understand the relations of the serum albumin level and its effects on the prognosis of the chronic diseases and outcome of the treatment if the patient is undergoing any. This study is intended to help the physician, surgeon and general practitioners to understand and intervene in the event and thus help the patient to recover earlier and in a better way. Aim of the study: is to estimate the mean serum albumin levels in hospitalised patients, to estimate the mean serum albumin levels in patients undergoing surgery and to correlate the serum albumin levels and the prognosis of the patient. Methods: This study was done in the Department of General Medicine at Kanachur Institute of Medical Sciences, Mangalore. This study was done from Jan 2017 to Dec 2018 The study is a cross – sectional study. The study is also double blinded and randomised. The study is a multi - level study. The sample size included one hundred patients. One hundred patients were identified in the department of Medicine. The patients were either chronically ill who were hospitalised for more than three weeks or who were undergoing treatment. The serum albumin levels were estimated. In chronically hospitalised patients the patients were divided into three groups 1. Serum levels less than 2 gm / Dl 2. Serum levels between 2 g/ dl and 5 gm / Dl 3. Serum levels more than 5 gm / Dl The serum albumin levels were again estimated and the prognosis was checked in the form of pain, worsening of symptoms, positive progression of disease, cure and death. In each group the necessary treatment was given in the form of nutrition supplementation and was observed for the prognosis. The serum albumin levels were again estimated and the prognosis was checked in the form of pain, worsening of symptoms, positive progression of disease, cure and death. Result: In the present study there is a significant difference in the prognosis of the patients when the serum albumin level increases in the serum. The mean serum levels in the three groups were found to be 1.95 gm / Dl, 2.85 gm / Dl and 5.1 gm / Dl. In the third group the cure was complete with treatment, showing the significance of serum albumin levels in the prognosis and outcome of the disease. Conclusion: The disease prognosis was significantly altered when the low serum albumin was altered.

English

Interest is renewed in herbal medicine since it is believed it has less side effects and is safer. In addition, there has been continued demand to obtain more drugs from plant sources to alleviate various ailments of mankind. This study is aimed at investigating the antimalarial activity in an herbal cocktail and individual plant extracts contained on Plasmodium berghei in infected Wistar rats. Thirty five Wistar rats randomly assigned into seven groups of five were used. The cocktail and individual aqueous extracts of Azadirachta indica, Mangifera indica, Carica papaya, and Citrus limon were orally administered to the infected Wistar rats weighing an average of 200 g at standard doses of 100 mg/kg/day for seven days, with the exception of aqueous leaf extract of A. indica which was administered at a dose of 10 mg/kg/day. The therapeutic effects of the cocktail and the individual extracts against P. berghei were investigated and the effects on the liver were histologically assessed. Biochemical assays for liver markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein (TP) and albumin (ALB) were also assessed. The results showed that the cocktail and individual extracts possess antimalarial activity, by reducing the degree of parasitaemia, inducing recovery of hepatic cells and reduction of malaria associated liver pathology. Administration of the extracts did not significantly alter the level of albumin and total protein, no increase was observed in AST activity (P > 0.05). Significant increase was observed in the ALT activities among the rats administered with the cocktail or that which contained extract (P < 0.0001). In conclusion, the cocktail and the individual extracts possess antimalarial activity, thus justifying their usage in traditional medical practice. Extensive studies for validation of various medicinal plants used in treating malaria should be further conducted Key words: Plasmodium berghei, cocktail, aspartate aminotransferase, alanine aminotransferase, total protein, albumin.

Features of diagnostics of the hepatobiliary system diffuse lesions in children with herpes viral infection caused by Epstein-Barr virus (both isolated and in the form of mixed herpesvirus infection)

Purpose: to improve the treatment quality and prognosis of herpesvirus infection in children caused by the Epstein-Barr virus (both isolated and in the form of mixed herpesvirus infection) based on the study of clinical, biochemical and immunological parameters of the hepatobiliary system. Materials and methods: We examined 95 children aged 3 to 7 years with herpesvirus infection, who were divided into three groups (the I group – children with acute Epstein-Barr infection, the II group – children with Epstein-Barr infection in combination with cytomegalovirus infection, the ІІІ group – children with Epstein-Barr infection and herpesvirus infection type 6). Age-matched healthy control group consisted of 20 children. The diagnosis was verified using a polymerase chain reaction. Biochemical studies included determination of total protein and its fractions, total bilirubin and its fractions, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, thymol index. All patients underwent echosonography of the liver. The level of cytokines (IL-1β, IL-4) and antiviral protection parameters – the content of natural killers (CD16+), T-helper (CD4 +) and/or cytotoxic lymphocytes (CD8 +) were evaluated. Results. In all examined children the disease started acutely from general intoxication syndrome, lesion of the nasopharynx and oropharynx, which were more pronounced in the children of the 1st and 2nd examined groups. Manifestations of the viral exanthema and enanthema were more commonly and pronounced in children of the III group. Most children (61.8 %) with Epstein-Barr infection in combination with herpesvirus infection type 6 had disturbances in the central nervous system. The lesions of lymphoid tissue occurred in 73 (76.7 %) children and were more prevalent in the 1st and 2nd surveyed groups. The constant symptom of the disease was hepatomegaly. Splenomegaly was observed in 82 (86.7 %) patients. We have noted an increase in the levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in the examined children. These changes were more pronounced in children of the 2nd group. Herewith, cytolysis of hepatocytes in most cases among children of all examined groups was not accompanied by hyperbilirubinemia. The jaundice of the skin and mucous membranes occurred only in 18.5% of all examined patients, who were diagnosed with moderate hyperbilirubinemia (60.0 ± 4.6 μmol/l). Proteinogram parameters in the examined patients in the acute period were characterized by a decrease in albumin content, an increase in the content of α1-, α2- and γ-globulins and a decrease in the albumin / globulin ratio. These indicators were significantly changed in the 2nd surveyed group. The majority of examined patients had coagulogram indices on average matched to the age norm. One third of patients showed moderately elevated fibrinogen levels. Immune disorders, that accompany the herpesvirus infection, are characterized by an imbalance of proinflammatory and anti-inflammatory cytokines. Indicators of portal hemodynamics in patients of the I group in the acute period of the disease were characterized by moderate changes such as a decrease in hepatic artery and portal vein blood flow without viscoelasticity and peripheral vascular resistance violations. In the II group the decrease in the diameter of the common hepatic artery and the increase in the diameter of the portal vein, the decrease in the vessels blood flow with a decrease in their viscoelasticity and peripheral vascular resistance was noted. In the III group of patients the hepatic artery and portal vein hemodynamic changes, which had a compensatory character, were identified. Conclusions: Taking into account the revealed clinical changes, it can be noted that lesions of the nasopharynx, more pronounced manifestations of intoxication and hepatolienal syndromes prevailed in infants with herpesvirus infection. Proinflammatory cytokines overactivity in patients with Epstein-Barr viral infection in combination with cytomegalovirus infection causes a longer intoxication period, pronounced liver enlargement, elevation of transaminases and inhibition of liver albumin synthesis. It could be reasonable to prescribe vasoactive therapy for patients with Epstein-Barr virus infection in combination with cytomegalovirus infection both in the acute and reconvalescence period of the disease followed by structural-functional and hemodynamic state of the liver monitoring at the stages of medical rehabilitation.

A 12-week evaluation of annatto tocotrienol supplementation for postmenopausal women: safety, quality of life, body composition, physical activity, and nutrient intake

BackgroundEvidence suggests that tocotrienols may benefit bone health in osteopenic women. However, their safety in this population has never been investigated. This study was to evaluate the safety of a 12-week supplementation of annato tocotrienol in postmenopausal osteopenic women, along with effects of the supplementation on quality of life, body composition, physical activity, and nutrient intake in this population.MethodsEighty nine postmenopausal osteopenic women were randomly assigned to 3 treatment arms: (1) Placebo (430 mg olive oil/day), (2) Low tocotrientol (Low TT) (430 mg tocotrienol/day from DeltaGold 70 containing 300 mg tocotrienol) and (3) High tocotrienol (High TT) (860 mg tocotrienol/day from DeltaGold 70 containing 600 mg tocotrienol) for 12 weeks. DeltaGold 70 is an extract from annatto seed with 70% tocotrienol consisting of 90% delta-tocotrienol and 10% gamma-tocotrienol. Safety was examined by assessing liver enzymes (aspartate aminotransferase, alanine aminotransferase), alkaline phosphatase, bilirubin, kidney function (blood urea nitrogen and creatinine), electrolytes, glucose, protein, albumin, and globulin at 0, 6, and 12 weeks. Serum tocotrienol and tocopherol concentrations were assessed and pills counted at 0, 6, and 12 weeks. Quality of life, body composition, physical activity, and dietary macro- and micro-nutrient intake were evaluated at 0 and 12 weeks. A mixed model of repeated measures ANOVA was applied for analysis.ResultsEighty seven subjects completed the study. Tocotrienol supplementation did not affect liver or kidney function parameters throughout the study. No adverse event due to treatments was reported by the participants. Tocotrienol supplementation for 6 weeks significantly increased serum delta-tocotrienol level and this high concentration was sustained to the end of study. There was no difference in serum delta-tocotrienol levels between the Low TT and the High TT groups. No effects of tocotrienol supplementation were observed on quality of life, body composition, physical activity, and nutrient intake.ConclusionsAnnatto-derived tocotrienol up to 600 mg per day for 12 weeks appeared to be safe in postmenopausal osteopenic women, particularly in terms of liver and kidney functions. Tocotrienol supplementation for 12 weeks did not affect body composition, physical activity, quality of life, or intake of macro- and micro-nutrients in these subjects.Trial registrationClinicalTrials.gov identifier: NCT02058420. Title: Tocotrienols and bone health of postmenopausal women.

Extrapolation of the Hepatic Clearance of Drugs in the Absence of Albumin In Vitro to That in the Presence of Albumin In Vivo: Comparative Assessement of 2 Extrapolation Models Based on the Albumin-Mediated Hepatic Uptake Theory and Limitations and Mechanistic Insights

The extrapolation of hepatic clearance (CL) from data determined in an in vitro assay in the absence of albumin (ALB) to that in the presence of ALB in liver in vivo was often inaccurate using traditional in vitro-to-in vivo extrapolation (IVIVE) methods for drugs binding to the ALB. It is recognized that considering an ALB-facilitated hepatic uptake phenomenon in the IVIVE can improve the extrapolation. Therefore, the present study provides a comparison of 2 existing models that account for the ALB-facilitated hepatic uptake phenomenon in the IVIVE of CL. These models assume an interaction of the ALB-bound drug complex with the hepatocyte membrane that enhanced the dissociation of the drug from ALB to result in increased unbound intracellular drug levels available for metabolism or transporter-mediated elimination. One model refers to the old facilitated-dissociation model (FDM), which is based on a binding isotherm and necessitates knowing the specific input parameters of the interaction (i.e., relative capacity of the interaction, dissociation constant, number of binding sites, and ALB concentration). The other model is based on the same theory but is recent and more speculative although it presumes that each interaction between the ALB-drug complex and the hepatocyte surface would at all times enhance and deliver the dissociated bound drug moiety into the hepatocytes and therefore, has the advantage to use less binding information. Consequently, this second model simply consists of adjusting the unbound fraction determined in plasma in vitro of each drug (fup-adjusted) with the real differential of ALB concentration between the plasma and liver in vivo to estimate the corresponding differential of ALB-drug complex also assumed available to deliver the unbound drug moiety for hepatic uptake in vivo versus in vitro. Application of these 2 models (FDM and fup-adjusted) significantly improved the IVIVEs of CL of drugs, and hence, the next step was to compare these 2 models with the same data set. Recently published data on the hepatic uptake of 2 organic anions, namely 1-anilino-8-naphthalene sulfonate and pitavastatin, provide all binding information. As expected, the results indicate that these 2 models are conceptually and mathematically equivalent as well as they successfully predicted the experimentally determined ratios of the unbound intrinsic CL (CLint) in the presence of ALB in vivo to that in the absence of ALB in vitro. However, the 2 models were equivalent particularly for pitavastatin because its ALB-drug complex showed a relevant capacity of interaction and dissociation with the hepatocyte membrane. Conversely, for 1-anilino-8-naphthalene sulfonate, the model of fup-adjusted overestimated the ratio of unbound CLint by contrast to the FDM model because its ALB-drug complex demonstrated a significantly lower capacity of interaction with the membrane. The rational is simply because the model of fup-adjusted presumably assumed an important facilitated-uptake phenomenon for each drug, whereas the FDM model was derived from binding data specific to each drug. Overall, these 2 models are complementary, and all contribute toward achieving the same objective of quantifying the ALB-facilitated uptake phenomenon; however, the FDM model is more specific, but its application necessitates collecting more binding data compared with the model of fup-adjusted that can be used prospectively to predict the maximal effect of the facilitated-hepatic uptake in IVIVE.

Complementary effect of Capparis spinosa L. and silymarin with/without praziquantel on mice experimentally infected with Schistosoma mansoni

SummarySchistosomiasis remains to be the most common fibrotic disease resulting from inflammation and deposition of scar tissue around trapped parasitic eggs in the liver. Though chemotherapy eradicates matured worms efficiently and prevents the accumulation of schistosome eggs, fewer effective drugs are directed to reverse the present hepatic fibrosis. Therefore, treatment targeting hepatic fibrosis associated with schistosomiasis remains a challenging proposition.The present study was designed to investigate the potential complementary schistosomicidal and hepatoprotective activities of the methanol extract of Capparis spinosa L. (C. spinosa) with or without praziquantel (PZQ) and compare results with silymarin (Milk thistle), a known hepatoprotective and antifibrotic agent, on induced liver fibrosis by experimental Schistosoma mansoni (S. mansoni) infection. Total polyphenols in the extract were determined using colorimetric assay.C. spinosa L. caused a partial decrease in worm burden; a statistically significant reduction in hepatic and intestinal tissue egg load, what was associated histopathologically with decreasing in both the number and diameter of granulomas, as well as restoring serum aminotransferases (AST & ALT), alkaline phosphatase (ALP) and improving liver albumin synthesis. The best results were obtained in the group of mice treated with C. spinosa L. and PZQ together. Quantitative estimation of total polyphenols content using colorimetric assay showed that C. spinosa L. leaves contain higher concentration of polyphenolic compounds than fruits.It was concluded that C. spinosa L. has a promising hepatoprotective and antifibrotic properties and could be introduced as a safe and effective therapeutic tool with PZQ in the treatment of schistosomal liver fibrosis. Nevertheless further studies on the mechanism of action of C. spinosa L. in chronic liver diseases may shed light on developing therapeutic methods in clinical practice.

Hepatoprotective Activity of Aruvadha churnam a Traditional Siddha Formulation against Paracetamol Induced Liver Damage in Rats

Background: Aruvadha Churnam, a Siddha formulation is commonly employed in Siddha system of medicine in management of hepatic ailments. Aim: The aim of the present study was to evaluate anti-hepatotoxic potential of Aruvadha Churnam against Paracetamol induced liver damage in Wistar Albino rats. Materials and Methods: Aruvadha Churnam at 360, 1800, and 2400 mg/kg/day, p.o. doses were administered orally to rats for 8 days. Silymarin (50 mg/kg body weight, p.o.) was used as a reference drug in the study. Single dose of Paracetamol (3 g/kg, p.o.) was administered on the 8th day after treatment. Animals were sacrificed 48 h after the administration of Paracetamol, and serumlevels of liver markers (SGOT, SGPT, ALP, Bilirubin), Cholesterol, Triglycerides, Creatinine, Total Protein and Albumin were measured. Livers were excised from animals for histopathological studies. Results: Pretreatment with different dosages of Aruvadha Churnamlowered the levels of the serum parameters when compared to the hepatotoxic control group, which indicates the regeneration of damaged hepatocytes and restoration of its normal functions. The formulation was found to be effective at 1800mg/kg bw (Intermediate dose)whereas 2400mg/kg bw (High dose) showed a ceiling effect. The biochemical observations were paralleled by histopathological findings in rat liver both in the case of paracetamol and treatment groups. Conclusion: The current investigation supports the claim that this traditional siddha formulation is used in the treatment of liver ailments and also provides scientific evidence for its protective effects against Paracetamol induced hepatic damage.

Diagnosis of dengue- an overview

The first investigation ordered on clinical suspicion of dengue is complete blood count. The classical dengue triad includes increased hematocrit, atypical plasmacytoidlymphocytosis and thrombocytopenia [1].Hemoconcentration (hematocrit elevated > 45% or by > 20% from previous value) is diagnostic of Dengue Hemorrhagic Fever. Further confirmation is usually made with Dengue Antigen test. During early stages of the disease around 4-5 days of fever onset, virus isolation, nucleic acid or antigen detection are used to diagnose the virus from serum, plasma or tissues. However serology remains the method of choice during convalescence. Other tests include antibody titre for dengue virus types, Polymerase chain reaction (PCR), Liver function tests, Serum protein & albumin levels & Coagulation panel.

Abolishment of proximal tubule albumin endocytosis does not affect plasma albumin during nephrotic syndrome in mice

The megalin/cubilin receptor complex is required for proximal tubular endocytosis and degradation of filtered albumin. An additional high-capacity retrieval pathway of intact albumin for the recovery of large amounts of filtered albumin has been proposed, possibly involving cooperation between megalin/cubilin and the neonatal Fc receptor. To clarify the potential role of such a pathway, we examined the effects of megalin/cubilin gene inactivation on tubular albumin uptake and plasma albumin levels in nephrotic, podocin knockout mice. Immunofluorescence microscopy of megalin/cubilin/podocin knockout mouse kidneys demonstrated abolishment of proximal tubule albumin uptake, in contrast to the excessive albumin accumulation observed in podocin knockout mice compared to controls. Correspondingly, urinary albumin excretion was increased 1.4 fold in megalin/cubilin/podocin compared to podocin knockout mice (albumin/creatinine: 226 vs. 157 mg/mg). However, no difference in plasma albumin levels was observed between megalin/cubilin/podocin and podocin knockout mice, as both were reduced to approximately 40% of controls. There were no differences in liver albumin synthesis by mRNA levels and protein abundance. Thus, megalin/cubilin knockout efficiently blocks proximal tubular albumin uptake in nephrotic mice but plasma albumin levels did not differ as a result of megalin/cubilin-deficiency, suggesting no significance of the megalin/cubilin-pathway for albumin homeostasis by retrieval of intact albumin.

Renal Clearable New NIR Probe: Precise Quantification of Albumin in Biofluids and Fatty Liver Disease State Identification through Tissue Specific High Contrast Imaging in Vivo.

Development of a highly photostable, renal clearable, and nontoxic new NIR probe (CyG) for precise quantification of albumin in different biofluids and liver targeted in vivo albumin visualization is demonstrated. CyG's inherent property to interact selectively with albumin among different biomolecules in intracellular environment with high degree of sensitivity helps CyG in targeted liver imaging. In addition to its long excitation/emission wavelengths (λex = 740 nm, λem = 804 nm), which are much above the biological tissue opaque window (400-700 nm) ensuring better photon penetration, diminished tissue autofluorescence and high contrasts, its molecular mass and size are far below the renal cutoff and hence, CyG qualifies as imaging material for clinical studies. We anticipate that CyG will provide new strategies to overcome the pitfall of present day albumin detection methods as well as accelerate the detection process at relatively lower costs without compromising the accuracy of detection. Moreover, the renal excretion kinetic and intrahepatic albumin binding affinity of CyG can further be used to differentiate between fatty liver from healthy liver in an experimentally arrived mouse model using noninvasive technique.

Transplantation of umbilical cord blood-derived mesenchymal stem cells to treat liver cirrhosis in mice: a comparison of tail and portal vein injection

Introduction: To date, there have been many studies indicating the positive effects of stem cells on treating liver cirrhosis. In this study, we used umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) for treatment in a mouse model of liver cirrhosis. Specifically, we determined and compared the effectiveness of two methods of MSC injection (tail vein versus portal vein).&#x0D; Methods: Liver cirrhosis in male Swiss mice (of age approximately 11 weeks or under) was induced by administration of carbon tetrachloride (CCl4; 1 ml/kg). One million UCB-MSCs were then transplanted into cirrhotic mice via the portal vein or tail vein. After 21 days, blood samples were collected for measurement of transaminase, bilirubin and albumin. The expression of fibrosis-associated genes, specifically procollagen – alpha 1 and integrin – beta1, were assessed using quantitative RT-PCR. The histopathology of the specimens was also evaluated using hematoxylin/eosin, Masson trichrome staining, and immunohistochemistry using collagen type 1 and alpha-SMA antibodies.&#x0D; Results: After 21 days, cirrhotic mice treated with UCB-MSCs showed recovery of bilirubin index, increase of liver albumin synthesis, inhibition of fibrosis-related gene expression (e.g. procollagen – alpha 1 and integrin – beta1), and remodeling of liver histology. From comparison of the different routes of transplantation, UCB-portal route was significantly more effective than UCB-tail route at reducing aspartate transaminase (AST) activity and bilirubin index (P&lt;0.05), and inhibiting procollagen – alpha 1 and integrin – beta1 expression (P&lt;0.05). UCB-MSCs from both transfusion routes showed accelerated improvement of liver histopathology.&#x0D; Conclusion: Therapeutic strategies using UCB-MSCs have proven to be promising for the treatment of liver cirrhosis. Injection of UCB-MSC via portal vein was more effective than tail vein for cirrhosis treatment.&#x0D; &#x0D; Peer Review Details&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Peer review method: Single-Blind (Peer-reviewers: 02) Peer-review policy&#x0D; Plagiarism software screening?: Yes&#x0D; Date of Original Submission: 17 August 2017&#x0D; Date accepted: 30 August 2017&#x0D; Peer reviewers approved by: Dr. Lili Hami &#x0D; Editor who approved publication: Dr. Phuc Van Pham&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Maternal Circulating Transthyretin Level Is Longitudinally Associated With Increased Risk of Gestational Diabetes Mellitus: It Is Not Just an Indicator of Nutritional Status

Transthyretin (TTR) is a carrier protein that transports thyroid hormones and retinol. Conventionally, a higher serum TTR level is usually taken as a sensitive clinical indicator of better protein nutritional status (1). However, emerging evidence has given us clues that TTR may contribute to gestational diabetes mellitus (GDM) (2–5). If this is the case, our previous “good impression” of TTR might be overturned. However, few population-based studies have focused on this issue. In this prospective cohort study, we measured serum TTR, total protein (TP), albumin (Alb), and other parameter levels in the regular antenatal liver and renal function (LRF) test at 13–20 gestational weeks in 1,914 pregnant women (aged 18–45 years) belonging to the ongoing Tongji Maternal and Child Health Cohort (TMCHC) study in China. All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethics review committee of Tongji Medical College of Huazhong University of Science and Technology and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Using logistic regression, we analyzed the association between …

Evaluation of hepatorenal impairments in Wistar rats coexposed to low-dose lead, cadmium and manganese: insights into oxidative stress mechanism

The study aims to evaluate effects of chronic low-dose coexposure to lead (Pb), cadmium (Cd) and manganese (Mn) on hepatorenal toxicity and oxidative stress. Young male Wistar rats were treated with Pb acetate (1.4 mg/kg BW), Cd chloride (0.01 mg/kg BW), Mn chloride (0.14 mg/kg BW) and their combination (Pb + Cd + Mn) by oral gavage, for 15 weeks. Liver enzymes, albumin (Alb), globulin (Glb), total protein, creatinine, urea and electrolyte concentrations were measured in the serum. Hepatic and renal malondialdehyde (MDA), glutathione peroxidase-1 (GPx1) and metallothionein-1 (MT1) concentrations were measured by enzyme immunoassay technique. Chronic exposure to the metals significantly (p < .05) increased serum Glb concentration and decreased Alb/Glb ratio, compared to the controls. Serum creatinine concentration significantly (p < .05) decreased in the Pb, Cd and Pb + Cd + Mn groups, but elevated in the Mn group. Hepatic MDAs rose significantly (p < .05) in the Pb group, while hepatic GPx1 activities increased significantly (p < .05) in the Cd, Mn and Pb + Cd + Mn groups. Hepatic and renal MT1 concentration decreased (p < .05) in the Mn group only. Biochemical alterations were confirmed by light microscopy of the liver and kidneys, which showed degenerative changes. It is concluded that prolonged coexposure to environmentally relevant levels of Pb, Cd and Mn impairs liver and kidney functions via the induction of oxidative stress, and it underlines the importance of studying toxicants in combination.

Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements.

Serum albumin concentration (CP) is a remarkably strong prognostic indicator of morbidity and mortality in both sick and seemingly healthy subjects. Surprisingly, the specifics of the pathophysiology underlying the relationship between CP and ill-health are poorly understood. This review provides a summary that is not previously available in the literature, concerning how synthesis, catabolism, and renal and gastrointestinal clearance of albumin interact to bring about albumin homeostasis, with a focus on the clinical factors that influence this homeostasis. In normal humans, the albumin turnover time of about 25 days reflects a liver albumin synthesis rate of about 10.5 g/day balanced by renal (≈6%), gastrointestinal (≈10%), and catabolic (≈84%) clearances. The acute development of hypoalbuminemia with sepsis or trauma results from increased albumin capillary permeability leading to redistribution of albumin from the vascular to interstitial space. The best understood mechanism of chronic hypoalbuminemia is the decreased albumin synthesis observed in liver disease. Decreased albumin production also accounts for hypoalbuminemia observed with a low-protein and normal caloric diet. However, a calorie- and protein-deficient diet does not reduce albumin synthesis and is not associated with hypoalbuminemia, and CP is not a useful marker of malnutrition. In most disease states other than liver disease, albumin synthesis is normal or increased, and hypoalbuminemia reflects an enhanced rate of albumin turnover resulting either from an increased rate of catabolism (a poorly understood phenomenon) or enhanced loss of albumin into the urine (nephrosis) or intestine (protein-losing enteropathy). The latter may occur with subtle intestinal pathology and hence may be more prevalent than commonly appreciated. Clinically, reduced CP appears to be a result rather than a cause of ill-health, and therapy designed to increase CP has limited benefit. The ubiquitous occurrence of hypoalbuminemia in disease states limits the diagnostic utility of the CP measurement.