Decrease In Serum Albumin Concentration Research Articles

The Impact of Methamphetamine on Liver Injury in Iraqi Male Addicts

Methamphetamine (METH) is a powerful stimulant that affects neurochemical processes controlling heart rate, appetite, blood pressure, body temperature, and wakefulness, making it highly susceptible to abuse. Liver enzymes such as ALT, AST, ALP, and GGT are crucial for liver function. Albumin, a protein synthesized by healthy liver cells, serves as an indicator of chronic liver disease. Additionally, hepatocytes produce bile acids, which are essential for the secretion of bile salts into the bile canaliculi. Disruption in this secretion results in the accumulation of bile salts in the canaliculi, leading to intrahepatic cholestasis. METH-induced liver toxicity involves disruptions in hepatic metabolism, oxidative stress, and increased body temperature, affecting cellular processes such as cell division and the cell cycle and potentially accelerating liver cell apoptosis. The study explores the link between liver toxicity and hepatocyte damage in Iraqi males suffering from addiction. This is a case-control study, conducted at Ibn-Rushed Psychiatric Hospital in Baghdad from July 2023 to February 2024, involved 196 males, with addiction durations exceeding 24 months with varying degrees of methamphetamine (METH) addiction. The study included 187 healthy male controls with no history of drug addiction. Participants were aged 18 to 40 years. Diagnosis was confirmed using a drug test screening card administered by a specialist. The study included liver function tests (ALT, AST, ALP, and GGT), total bilirubin, and albumin concentration assessments. Significant differences were observed between the addicts and controls, particularly a marked decrease in serum albumin concentration in the addicted males. The ROC curve classification model at various thresholds demonstrated that liver enzymes, especially ALT, ALP, and GGT, exhibited increased sensitivity to METH addiction. A histopathological examination was conducted on a deceased 38-year-old male who had a six-year history of chronic amphetamine addiction to confirm liver injury and the resulting elevation of liver enzymes. The findings of this study indicate that METH greatly affects liver function, suggested to the importance of following a preventative measures and effective treatment approaches for monitoring METH addiction progress.

Exploration of Risk Factors of the Onset of Antibiotics-induced Acute Kidney Injury and Its Transfer to Chronic Kidney Disease Using the Medical Information Database

Drug-induced acute kidney injury (AKI) is a serious adverse drug reaction, which results in a significant decline in renal function and is known to progress to chronic kidney disease (CKD). Therefore, appropriate drug therapy is important to avoid the risk of drug-induced AKI and CKD, which are serious concerns in clinical practice. In this study, using the medical information database of Hamamatsu University Hospital, we investigated the risk factors that accelerate the onset of drug-induced AKI or its progression to CKD in patients who received aminoglycoside antibiotics (AGs) or glycopeptide antibiotics (GPs), which are strongly associated with drug-induced AKI and CKD. We performed logistic regression analysis using patients' background, laboratory test results, and concomitant drug use, among other such factors as explanatory variables and drug-induced AKI or CKD onset as objective variables to explore the risk factors for drug-induced AKI and CKD. Our results showed that co-administration of amphotericin B, piperacillin-tazobactam and other AGs and GPs, increased serum creatinine (Scr) and chloride concentrations, serum lactate dehydrogenase activity, and decreased serum albumin concentration were risk factors for drug-induced AKI onset. Moreover, a reduced blood urea nitrogen:Scr ratio at drug-induced AKI onset served as a risk factor for CKD. These results suggest that careful monitoring of the aforementioned factors is important to ensure appropriate usage of these drugs in patients treated with AGs and GPs.

Association of dietary inflammation with tooth loss and cognitive decline in older adults from cross-sectional data: The moderated role of albumin

ObjectiveGrowing evidence suggests a potential connection between tooth loss and cognitive function in recent years. Increasing studies have focused on their inter-relationship, however, the underlying mechanism has yet to be fully elucidated. Few studies have considered the role of dietary inflammation and serum albumin in the association between tooth loss and cognitive function. Therefore, the aim of this study was to explore the role of dietary inflammation and serum albumin in the association between tooth loss and cognitive impairment. MethodsA sample of 1,009 US adults from the National Health and Nutrition Examination Survey (NHANES) provided data on oral condition, cognitive function, dietary intake, and serum tests. The association between tooth loss (exposure variable) and cognitive function (outcome variable) was assessed by linear regression. Furthermore, a moderated mediation model was established to examine the influence of dietary inflammation on the association between tooth loss and cognitive tests, and the visualization of the moderating effect of serum albumin concentration was displayed through the Johnson-Neyman curve. ResultsParticipants with impaired dentition had worse cognitive function and a higher Dietary Inflammation Index (DII). DII was highly correlated with Immediate Recall Test (IR), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST), which mediated 16.46 %, 14.41 % and 11.28 % of the effect between tooth loss and cognitive functions. Additionally, the relationship between DII and DSST was moderated by serum albumin concentration. ConclusionTooth loss was associated with cognitive function which was affected by pro-inflammatory dietary patterns and serum albumin level. Clinical significanceThis study presents evidence for dentists that dietary pattern change due to tooth loss plays a role in cognitive deterioration, which can also be moderated by serum albumin level. Therefore, the preservation of natural teeth is important for cognitive function, especially in an immunocompromised population with decreased serum albumin concentrations.

The Effects of Probiotic Lactobacillus rhamnosus GG on Fecal Flora and Serum Markers of Renal Injury in Mice with Chronic Kidney Disease.

In this study, we analyzed intestinal flora in an experimental mouse model of chronic kidney disease (CKD) and investigated whether oral supplementation with probiotic Lactobacillus rhamnosus GG could slow the decline in renal function and inflammatory status of mice with CKD. We surgically induced chronic kidney disease in C57BL/6J male mice aged 8-9 weeks. We used dual-stage 5/6 nephrectomy for this, while the mock group underwent a mock procedure. The experimental (CKD mice) and mock group were administered a daily dose of 10 × 109 colony forming unit (CFU) of probiotic L. rhamnosus GG or 2 g of maltodextrin as a placebo by oral gavage, respectively, for 5 weeks. At the end of the experiment, the fecal samples of the mice were collected and prepared for intestinal microbial diversity analysis. We examined the serum chemistry and renal histology of the mice. Important serum and blood biomarkers were associated with the development of CKD, including increased serum concentrations of creatine, cystatin C, blood urea nitrogen (BUN), and a protein-interleukin-6 (denoted as IL-6), whereas decreased serum albumin concentration was also observed in the mice with CKD. The intestinal flora of the mice with CKD significantly declined in terms of diversity, richness, and homogeneity. The consumption of L. rhamnosus GG probiotic via oral gavage significantly decreased the serum concentration level present in creatinine and blood urea nitrogen. However, it increased albumin in the group with CKD. After probiotic treatment, serum IL-6 levels dropped considerably, and the kidney histopathology score in mice with CKD who were given L. rhamnosus GG improved. Moreover, supplementation with the probiotic significantly improved floral richness and lineage diversity in the mice with CKD.Conclusions: In this study, we found that probiotics significantly attenuated renal failure development, reduced serum levels of proinflammatory cytokine IL-6, and increased the abundance and lineage diversity of intestinal flora in mice with chronic kidney disease.

Increased dietary Trp, Thr, and Met supplementation improves growth performance and protein deposition of salmonella-challenged growing pigs under poor housing conditions.

Highly intensified rearing conditions and precarious sanitary management predispose pigs to immune system activation, altered amino acid (AA) metabolism, and decreased growth performance. Thus, the main objective of this study was to evaluate the effects of increased dietary tryptophan (Trp), threonine (Thr), and methionine + cysteine (Met + Cys) supplementation on performance, body composition, metabolism, and immune responses of group-housed growing pigs under challenging sanitary conditions. A hundred and twenty pigs (25.4 ± 3.7 kg) were randomly assigned to a 2 × 2 factorial arrangement, consisting of two sanitary conditions (SC, good [GOOD] or salmonella-challenge and poor housing condition [Salmonella Typhimurium (ST) + POOR]) and two diets, control (CN) or supplemented with AA (Trp, Thr, and Met + Cys:Lys ratios 20% higher than those of the CN diet [AA>+]). Pigs were followed during the growing phase (25-50 kg) and the trial lasted 28 d. The ST + POOR SC pigs were challenged with Salmonella Typhimurium and raised in a poor housing condition. The ST + POOR SC increased rectal temperature, fecal score, serum haptoglobin, and urea concentration (P < 0.05) and decreased serum albumin concentration (P < 0.05) compared with GOOD SC. Body weight, average daily feed intake, average daily gain (ADG), feed efficiency (G:F), and protein deposition (PD) were greater in GOOD SC than in ST + POOR SC (P < 0.01). However, pigs housed in ST + POOR SC fed with AA+ diet had lower body temperature (P < 0.05), increased ADG (P < 0.05) and nitrogen efficiency (P < 0.05), and a tendency for improved PD and G:F (P < 0.10) compared with CN diet fed pigs. Regardless of the SC, pigs fed AA+ diet had lower serum albumin (P < 0.05) and tended to decrease serum urea levels (P < 0.10) compared with CN diet. The results of this study suggest that the ratio of Trp, Thr, and Met + Cys to Lys for pigs are modified by sanitary conditions. Furthermore, supplementation of diets with a blend of Trp, Thr, and Met + Cys improves performance, especially under salmonella-challenge and poor housing conditions. Dietary tryptophan, threonine, and methionine supplementation can modulate immune status and influence resilience to sanitary challenges.

Effects of the Malnutrition-Eat Additional Meal (MEAM) Diet on the Serum Levels of Albumin and C-Reactive Protein in Hemodialysis Patients.

The main objective of this project was to evaluate the efficiency of two kinds of nutritional intervention implemented in hemodialysis patients for 24 weeks (traditional nutritional intervention without a meal served before dialysis for group HG1, and nutritional intervention involving a meal served before dialysis for group HG2), and their impact on nutritional status and serum concentrations of C-reactive protein (CRP). Nutritional status and serum biochemical parameters were analyzed in the control group (CG, n = 70) and in two homogeneous groups of patients, HG1 (n = 35) and HG2 (n = 35). There was an interesting trend in both groups of patients connected with increased intake, mainly of energy and protein. In HG1, the greatest increase in energy intake was observed on Sundays, and in HG2 on the days with dialysis. In HG2, after 24 weeks of the nutritional intervention, an increase in serum albumin (p = 0.0157) and a decrease in CRP concentration (p = 0.0306) were observed, whereas in HG1 there was a decrease in serum albumin concentration (p = 0.0043) with no significant change in CRP concentration. The nutritional intervention applied, called the Malnutrition-Eat Additional Meal (MEAM) diet with an easily digestible meal served before dialysis, was aimed at improving the patients' nutritional status and the obtained results indicate the need not only for substantial reeducation of hemodialysis patients in the area of their diet, but also for undertaking further research and discussions on the possibility of ensuring adequate meals for hemodialysis patients before the dialysis procedure.

Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis

Dialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β2-microglobulin (β2m). Although high serum β2m levels and a long dialysis vintage are the primary and secondary risk factors for the onset of DRA, respectively, patients with these do not always develop DRA, indicating that there are additional risk factors. To clarify these unknown factors, we investigate the effects of human sera on β2m amyloid fibril formation, revealing that sera markedly inhibit amyloid fibril formation. Results from over 100 sera indicate that, although the inhibitory effects of sera deteriorate in long-term dialysis patients, they are ameliorated by maintenance dialysis treatments in the short term. Serum albumin prevents amyloid fibril formation based on macromolecular crowding effects, and decreased serum albumin concentration in dialysis patients is a tertiary risk factor for the onset of DRA. We construct a theoretical model assuming cumulative effects of the three risk factors, suggesting the importance of monitoring temporary and accumulated risks to prevent the development of amyloidosis, which occurs based on supersaturation-limited amyloid fibril formation in a crowded milieu.

Utilidad del proteinograma electroforético capilar en el diagnóstico de la Peritonitis Infecciosa Felina (PIF) no efusiva: estudio de caso

Feline infectious peritonitis (PIF) is an infectious disease which has a high mortality rate compared to other infectious diseases among feline population. It clinically manifested under two forms, effusive or non-effusive. PIF’s diagnosis, mainly the non-effusive form, is a clinical challenge based on symptoms, viral detection and laboratory findings. In this regard, the albumin/globulin ratio and the increase on the γ globulin fraction of the capillary zone electrophoresis (PEF) are important and complementary indicators for the antemortem diagnosis of PIF. This job’s objective was to exhibit a feline clinical case clinically diagnosed with non-effusive PIF in which the PEF, along with other complementary routine tests, allowed to reach a definitive diagnosis. PEF’s results showed a polyclonal peak on the γ globulin fraction, a decreased serum albumin concentration and an albumin/globulin ratio of 0,23. Based on these results we discuss how the PEF, mainly on the non-effusive form of PIF, can support this disease diagnosis allowing to dictate an accurate prognosis and helping the clinical veterinarian on therapeutic decisions.

Clinical factors affecting cerebral oxygenation in patients undergoing peritoneal dialysis.

Although cerebral regional oxygen saturation (rSO2) is significantly lower in hemodialysis (HD) patients than that in healthy controls, investigations on cerebral oxygenation in peritoneal dialysis (PD) patients are limited. We aimed to confirm the cerebral oxygenation status and identify the factors affecting cerebral rSO2 in PD patients. Thirty-six PD patients (21 men and 15 women; mean age, 62.8 ± 12.7 years) were recruited. In addition, 27 healthy volunteers (17 men and 10 women; mean age, 43.5 ± 18.8 years) were recruited as a control group. Cerebral rSO2 was monitored at the forehead using an INVOS 5100c oxygen saturation monitor. Cerebral rSO2 was significantly lower in PD patients than that in healthy controls (57.0 ± 7.3% vs 68.9 ± 8.6%, p < 0.001); moreover, cerebral rSO2 was significantly correlated with natural logarithm (Ln)-PD duration (r = -0.389, p = 0.019) and serum albumin concentration (r = 0.370, p = 0.026) in a simple linear regression analysis. Multivariable linear regression analysis was performed using variables that showed a significant correlation and p < 0.20 (serum creatinine, serum sodium, Ln-C-reactive protein, and dosage of erythropoiesis-stimulating agent) with the cerebral rSO2. Cerebral rSO2 was independently associated with Ln-PD duration (standardized coefficient: -0.339) and serum albumin concentration (standardized coefficient: 0.316). Cerebral rSO2 was significantly affected by the PD duration and serum albumin concentration. Further prospective studies are needed to clarify whether preventing a decrease in serum albumin concentration leads to the maintenance of cerebral oxygenation in patients undergoing PD.

Therapeutic efficacy of a Dioscorea membranacea extract in a rat model of hepatocellular carcinoma: Histopathological aspects

Hepatocellular carcinoma (HCC) is most common in adults and has a high mortality rate because of a lack of effective treatment options. We investigated the effect of a medicinal plant as a potential source of drugs against HCC. The rhizomes of Dioscorea membranacea Pierre (DM), Hua-Khao-Yen in Thai, are commonly used as ingredients for alternative treatment of cancer in Thailand. In this study, the anticancer effects of DM extract in HCC-bearing rats were evaluated with respect to gross morphology, histopathology, and leakage of liver enzymes. In untreated HCCs, typical features of liver cancer, including hepatic nodules, thick-cell cords, and pseudoglandular cell arrangements, were observed. In addition, the HCCs showed abnormal reticulin patterns and a high glypican3 expression. In HCC-bearing rats treated with DM the cancer areas and reticulin expression were significantly reduced compared to the untreated group (p < 0.01). Sorafenib, the standard drug to treat HCC, reduced the cancer area further, but increased leakage of liver enzymes and decreased serum albumin concentration, indicating liver toxicity. These findings suggest that DM has an anticancer effect on HCCs in an animal model in vivo with potentially less severe side effects than sorafenib. Therefore, further studies of DM’s mechanism of action in HCC should be carried out.

Arrival cortisol measurement in veal calves and its association with body weight, protein fractions, animal health and performance

Male dairy calves are exposed to an accumulation of transport, social and environmental stressors while transferred to fattening units. As a consequence, calves show high cortisol concentrations upon arrival at the veal facility. Whether cortisol levels as measured on arrival can be associated with animal health, welfare and production results is currently unknown.The first objective of this prospective cohort study was to determine possible associations of arrival serum cortisol concentration with health and production variables of veal calves and other arrival predictors like body weight and γ-globulin concentration. The second aim was to investigate potential clustering of arrival risk factors in veal calves for developing bovine respiratory disease (BRD) based on arrival body weight, serum cortisol concentration, total protein and protein fractions. In total, 105 male Holstein calves from two consecutive production cycles in a single, commercial white veal farm were blood sampled directly at arrival on the farm to determine serum cortisol, total protein and protein fractions. All calves were weighed the day after arrival and clinical signs, average daily weight gain (ADG) and carcass weight were collected. Also, all calves of both production cohorts were repeatedly examined by thoracic ultrasonography at the onset of group respiratory disease symptoms (2−3 weeks after arrival) and four weeks later. Linear and logistic mixed models together with k-means clustering were used for statistical analyses.Calves showed on average high, but individually variable serum cortisol concentrations (mean value = 96.6 ng/mL ± standard deviation (SD) = 48.8; Range (R) = 50.0−317 ng/mL). Arrival cortisol, body weight and γ-globulin content were not significantly associated. Serum cortisol and albumin concentrations at arrival were associated with chronic, unresponsive pneumonia. For each increase of serum cortisol concentration by 10 ng/mL, the odds for lung consolidation of ≥1 cm in depth at the second ultrasonography increased, odds ratio (OR) = 1.03 (95 % confidence interval (CI) = 1.01–1.06; P < 0.050). For every decrease in serum albumin concentration by 1g/L, the OR for developing pneumonia was 1.23 (95 % CI= 1.04–1.46; P < 0.015). Additionally, two clusters of calves were identified based upon arrival status: a low risk cluster with below average stress-induced cortisol values, above average body weight, no acute phase response (APR) and no failure of passive immune transfer (FPIT), and a high risk cluster with above average cortisol values, below average body weight, APR and FPIT. High risk calves had higher odds for developing clinical BRD (OR= 3.88 (95 % CI=1.20−12.53; P < 0.020)) and lung consolidation ≥1 cm in depth at week 6−7 after arrival (OR= 3.93 (95 % CI=1.34−11.53; P < 0.013)).Avoiding high cortisol levels upon arrival of calves is important for animal welfare, but also for reduction of the prevalence of chronic, unresponsive pneumonia and the associated need for (repeated) antimicrobial treatment and production losses.

Synergistic curative effect of Boswellic acid and Cisplatin against Diethyl nitrosamine -induced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a primary malignancy of hepatocyte. Boswellic acids are the effective components of gum resin of Boswellia serrata, which have anti-inflammatory properties. Cisplatin is used as a chemotherapeutic agent for treatment of HCC. The present study aims to evaluate the role of Boswellic acid in HCC treatment and as a chemo-sensitizer for Cisplatin treatment of HCC in rats that is induced by orally administration of Diethyl nitrosamine (DEN). Sixty rats were divided in to sex groups, 10 rats each, group 1: normal control group, group 2: cisplatin (1.5 mg/Kg b.wt), group 3: received the Diethyl nitrosamine (DEN) (20 mg/kg b.wt), group 4: received DEN as in group 3 and then treated with cisplatin, group 5: received DEN as in group 3 and then treated with Boswellic acid (500 mg/kg b.wt) and group 6: received DEN as in group 3 and then treated with cisplatin and Boswellic acid. After 10 weeks animals were sacrificed and liver tissue were removed for Histopathological and tissue parameters examination. A significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, a significant decrease in serum albumin concentration. Also a significant increases in liver transforming growth factor-beta 1 (TGF-b1), B-cell lymphoma 2 (Bcl-2) and nuclear factor kappa β (NF-kβ) concentrations and a significant decrease in Caspase.3 activity were recorded in DEN-treated rats while treatment with Boswellic acid and Cisplatin reduced the severity of HCC and enhanced histopathological findings, these result suggesting the efficacy of Boswellic acid supplementation as an anti-HCC.

The potential therapeutic effect of Luteolin against Diethyl nitrosamine induced hepatocellular carcinoma in rats.

Hepatocellular carcinoma (HCC) is one of the main causes leading to cancer mortality. Luteolin derived from celery and has anti-cancer activity. Cisplatin is used as a chemotherapeutic agent for the treatment of HCC. A major problem with Cisplatin is the development of Cisplatin chemo resistance. This study aims to evaluate the role of Luteolin in HCC treatment and as a chemo-sensitizer for Cisplatin treatment of HCC in rats. Sixty rats were divided in to sex groups, 10 rats each, group 1: normal control group, group 2: cisplatin (1.5 mg/Kg b.wt) for four weeks and group 3: received the Diethyl nitrosamine (DEN) (20 mg/kg b.wt), group 4: received DEN as in group 3 and then treated with cisplatin, group 5: received DEN as in group 3 and then treated with Luteolin (0.2 mg/kg b.wt) and group 6: received DEN as in group 3 and then treated with cisplatin and Luteolin. After 10 weeks animals were sacrificed and liver tissue were removed for Histopathological and tissue parameters examination. A significant increase in serum serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, a significant decrease in serum albumin concentration. Also a significant increases in liver transforming growth factor-beta 1 (TGF-b1), B-cell lymphoma 2 (Bcl-2) and nuclear factor kappa β (NF-kβ) concentrations and a significant decrease in Caspase.3 activity were recorded in DEN-treated rats while treatment with Luteolin and Cisplatin reduced the severity of HCC and enhanced histopathological findings, these result suggesting the efficacy of Luteolin supplementation as an anti-HCC.

Lycopene Attenuated Nitrosodiethylamine-Induced Hepatocarcinogenesis by Modulating the Metabolic Activation and Detoxification Enzymes

Lycopene was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and anticancer activity. This study was done to investigate the protective effects of Lycopene on diethylnitrosamine (DEN)- induced hepatocarcinogensis in rats. Forty-five male albino rats were divided into three groups. Group I (normal control group): rats administered distilled water only. Group II: rats received diethylnitrosamine (200 mg/kg b.wt/i.p), two weeks later rats received (2 ml/kg b. wt) Carbon tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl4 injections were repeated once again after 1 month from first DEN injection. Group III: rats received DEN+CCl4 as in group II then treated with lycopene at a dose of (20 mg/kg b.wt/orally) dissolved in tween-80% for 6 weeks. All animals were sacrificed after the end of experiment. DEN induced HCC showed significant increase in hepatic marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease in serum albumin concentration. Also, the results of molecular analysis in liver tissue revealed significant up-regulation in TNF-α gene expression level. Conversely, down-regulation in tumor suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with lycopene to DEN induced HCC protects the liver cells from damage by regulating the biochemical parameters. Lycopene was able to mitigate liver tissue damage induced by DEN through increasing of Cyp2E1 and P53 in addition to decreasing TNF-α gene expression level and ameliorate all serum liver function parameters. These findings suggested, the potential efficacy of lycopene as an additional chemo preventive agent in treatment of hepatocellular carcinoma by modulating the apoptosis, anti-inflammatory and detoxification effects.

Proanthocyanidin inhibit the development of diethylnitrosoamine induced premalignant phenotype in rat chemical hepatocarcinogensis model

Proanthocyanidin was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and anticancer activity. This study was done to investigate the protective effects of Proanthocyanidin on Diethylnitrosamine induced hepatocarcinogensis in rats. Fourty five male albino rats were divided into three groups. Group Ӏ: (normal control group): rats administered distilled water only. Group II: rats received Diethylnitrosamine (200 mg/kg b.wt/i.p), 2 weeks later rats received (2 ml/kg b.wt) Carbon tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl4 injections were repeated once again after 1 month from the first DEN injection. Group III: rats received DEN+CCl4 then treated with proanthocyanidin at a dose of (100 mg/kg b.wt/orally) dissolved in DMSO 7% for 6 weeks. All animals were sacrificed after the end of experiment. DEN induced HCC showed significant increase in hepatic marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease in serum albumin concentration. Also, the results of molecular analysis in liver tissue revealed significant up-regulation in TNF-α gene expression level. Conversely, down-regulation in tumor suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with proanthocyanidin to DEN induced HCC protects the liver cells from damage by regulating the biochemical parameters. The obtained results suggest that proanthocyanidin can inhibit the proliferation of HCC cells through inducing tumor cell apoptosis via activation of the p53 pathway and detoxification enzyme Cyp2E1 and inhibition of TNF-α overexpression. Proanthocyanidin may thus be used as a potentially promising agent to inhibit HCC cell proliferation and may be a novel natural product for the management treatment of HCC.

Spirullina inhibit the development of diethylnitrosoamine induced premalignant phenotype in rat chemical hepatocarcinogensis model

Spirulina was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and anticancer activity. This study was done to investigate the protective effects of spirullina on DEN induced hepatocarcinogensis in rats. Fourty-five male albino rats were divided into three groups. Group Ӏ :(normal control group): rats administered distilled water only. Group II: rats received diethylnitrosoamine (200 mg/kg b.wt/i.p), 2 weeks later rats received (2 ml/kg b.wt) Carbon tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl4 injections were repeated once again after 1 month from first DEN injection. Group III: rats received DEN then treated with spirullina platensis at a dose level of (800 mg/kg b.wt/orally) dissolved in distilled water for 6 weeks. DEN induced HCC showed significant increase in hepatic marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease in serum albumin concentration. Also, the results of molecular analysis in liver tissue revealed significant up-regulation in TNF-α gene expression level. Conversely, down-regulation in tumor suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with spirullina platensis to DEN induced HCC protects the liver cells from damage by regulating the biochemical parameters. Spirullina platensis was able to mitigate liver tissue damage induced by DEN through increasing of Cyp2E1 and P53 in addition to decreasing TNF-α gene expression level and ameliorate all serum liver function parameters. The obtained results suggest spirullina platensis can inhibit the proliferation of HCC cells through inducing tumor cell apoptosis via activation of the p53 pathway, improvement of detoxification Enzyme and suppression of inflammation by inhibition of TNF-α overexpression. Spirullina may thus be used as a potentially promising agent to inhibit HCC cell proliferation and may be a novel natural product for the management of HCC.

Hypoalbuminemia: a price worth paying for improved dialytic removal of middle-molecular-weight uremic toxins?

Hemodiafiltration (HDF) increases the removal of middle-molecular-weight uremic toxins and may improve outcomes in patients with end-stage kidney disease (ESKD), but it requires complex equipment and comes with risks associated with infusion of large volumes of substitution solution. New high-flux hemodialysis membranes with improved diffusive permeability profiles do not have these limitations and offer an attractive alternative to HDF. However, both strategies are associated with increased albumin loss into the dialysate, raising concerns about the potential for decreased serum albumin concentrations that have been associated with poor outcomes in ESKD. Many factors can contribute to hypoalbuminemia in ESKD, including protein energy wasting, inflammation, volume expansion, renal loss and loss into the dialysate; of these factors, loss into the dialysate is not necessarily the most important. Furthermore, recent studies suggest that mild hypoalbuminemia per se is not an independent predictor of increased mortality in dialysis patients, but in combination with inflammation it is a poor prognostic sign. Thus, whether hypoalbuminemia predisposes to increased morbidity and mortality may depend on the presence or absence of inflammation. In this review we summarize recent findings on the role of dialysate losses in hypoalbuminemia and the importance of concomitant inflammation on outcomes in patients with ESKD. Based on these findings, we discuss whether hypoalbuminemia may be a price worth paying for increased dialytic removal of middle-molecular-weight uremic toxins.

Impact of serum albumin levels on long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset acute myocardial infarction

BackgroundTo evaluate the association of serum albumin (SA) with long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset acute myocardial infarction (AMI). MethodsThe cohort study enrolled 2305 patients with first-onset AMI. The median follow-up was of 1088days (3years). Impacts of SA on long-time mortality after AMI were determined using multivariate Cox proportional hazard regression analysis with backward selection. ResultsThe patients were divided into three categories by SA tertiles (≤3.62, 3.63–4.08, >4.08g/dl). High tertile group was used as reference, the adjusted HRs for all-cause death were 1.21 (P=0.338) and 1.74 (P=0.003) for intermediate and low tertile, respectively (p-for-trend=0.001); The equivalent values for cardiovascular death were 1.13 (P=0.588) and 1.64 (P=0.022), respectively (p-for-trend=0.009); The corresponding values for cardiac death were 1.07 (P=0.806) and 1.59 (P=0.048), respectively (p-for-trend=0.022). Moreover, adjusted HRs per 1-g/dl decrease in SA concentrations were 1.66 (P=0.001) for all-cause death, 1.47 (P=0.024) for cardiovascular death, and 1.61 (P=0.012) for cardiac death. ConclusionsLow SA level (≤3.62g/dl) on admission was an independent predictor of long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset AMI. There was a dose–response relationship between decreased SA concentrations and increased long-term all-cause, cardiovascular, and cardiac mortality.

Differential effects of hepatic cirrhosis on the intrinsic clearances of sorafenib and imatinib by CYPs in human liver

The tyrosine kinase inhibitors sorafenib and imatinib are important in the treatment of a range of cancers but adverse effects in some patients necessitate dosage modifications. CYP3A4 has a major role in the oxidation of sorafenib to its N-oxide and N-hydroxymethyl metabolites and also acts in concert with CYP2C8 to mediate imatinib N-demethylation. CYP3A4 expression and function are impaired in patients with advanced liver disease, whereas the functions of CYP2C enzymes are relatively preserved. We evaluated the biotransformation of sorafenib and imatinib in well-characterized microsomal fractions from 17 control subjects and 19 individuals with hepatic cirrhosis of varying severity. The principal findings were that liver disease impaired the microsomal oxidation of sorafenib to its major metabolites to 40–44% of control (P<0.01), whereas the N-demethylation of imatinib was relatively unimpaired. The impairments in sorafenib biotransformation were correlated with decreased serum albumin concentrations and increased serum bilirubin concentrations in patients with liver disease, but not with the overall grade of liver disease according to the Child-Pugh system. In contrast, there was no relationship between imatinib N-demethylation and clinicopathologic factors in liver disease patients. These findings were accounted for in terms of the differential roles of CYPs 3A4 and 2C8 in the intrinsic clearance of the drugs. CYP3A4 has the major role in the intrinsic clearance of sorafenib but plays a secondary role to CYP2C8 in the intrinsic clearance of imatinib. In agreement with these findings CYP2C protein expression and CYP2C8-mediated paclitaxel 6α-hydroxylation were unimpaired in cirrhotic livers. This information could be adapted in individualized approaches such as in vivo CYP3A4 phenotyping to optimize sorafenib safety and efficacy in cancer patients with liver dysfunction.

Long-term clinical impact of serum albumin in coronary artery disease patients with preserved renal function

Background and aimsLow serum albumin level is reportedly associated with worse clinical outcomes in patients with chronic kidney disease (CKD). However, associations between decreased serum albumin level and outcomes in non-CKD patients with coronary artery disease (CAD) remain unclear. Therefore, we aimed to evaluate the prognostic value of serum albumin concentrations in stable CAD patients with preserved renal function. Methods and resultsWe studied 1316 patients with CAD and preserved renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2) who underwent their first PCI between 2000 and 2011 and had data available for pre-procedural serum albumin. Patients were assigned to quartiles based on pre-procedural albumin concentrations. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. Mean albumin concentration was 4.1 ± 0.4 g/dL. During the median follow-up of 7.5 years, 181 events occurred (13.8%). Kaplan–Meier curves revealed that patients with decreased serum albumin concentrations showed a higher event rate for MACE (log-rank, p < 0.0001). Using the highest tertiles (>4.3 g/dL) as reference, adjusted hazard ratios were 1.97 (95% CI, 1.12–3.55), 1.77 (95% CI, 0.99–3.25), and 1.19 (95% CI, 0.68–2.15) for serum albumin concentrations of <3.9, 3.9–4.0, and 4.1–4.3 g/dL, respectively. Decreased serum albumin concentration was associated with MACE even after adjusting for other independent variables (HR, 2.21 per 1-g/dL decrease; 95% CI, 1.37–3.56, p = 0.001). ConclusionDecreased serum albumin concentration independently predicted worse long-term prognosis in non-CKD patients after PCI. Pre-procedural serum albumin concentration could offer a useful predictor for patients with CAD and preserved renal function.