Hepatic Reserves Research Articles

Effects of angler’s groundbaits on fish physiology and growth

Although angler’s groundbaits (GBs) can be an important food resource for fish, we do not know much about the effects of GB consumption on the growth and health of fish. To fill this knowledge gap, we conducted a controlled, six-week long feeding trial (feeding ration: 2% of body weight) with common carp at 22 °C (Cyprinus carpio, mean initial body weight: 557 g) to test the effect of two GBs composed mostly of animal-derived ingredients (AN-GBs) and two plant-based GBs (PL-GBs) relative to one aquaculture feed, as a control (five treatment altogether). Consumption of PL-GBs resulted in lower growth rate than AN-GBs, presumably due to the low protein content. However, the unit biomass increment per unit nitrogen input was higher in PL-GBs. Although PL-GBs resulted in reduction of hepatic energy reserves, hepatosomatic index, viscerosomatic index, and body condition did not differ among the treatments. We did not find differences in expression of inflammatory cytokines in the liver. In conclusion, AN-GBs more effectively increases the carrying capacity of fisheries, but fish sequester a higher portion of nitrogen content of PL-GBs –PL-GB input can be more effectively counterbalanced by fish removal. Finally, the GB consumption does not pose a health risk to fish.

Intermittent hypoxia exacerbates metabolic dysfunction-associated fatty liver disease by aggravating hepatic copper deficiency-induced ferroptosis.

Intermittent hypoxia (IH) is an independent risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD). Copper deficiency can disrupt redox homeostasis, iron, and lipid metabolism. Here, we investigated whether hepatic copper deficiency plays a role in IH-associated MAFLD and explored the underlying mechanism(s). Male C57BL/6 mice were fed a western-type diet with adequate copper (CuA) or marginally deficient copper (CuD) and were exposed separately to room air (RA) or IH. Hepatic histology, plasma biomarkers, copper-iron status, and oxidative stress were assessed. An in vitro HepG2 cell lipotoxicity model and proteomic analysis were used to elucidate the specific targets involved. We observed that there were no differences in hepatic phenotypes between CuA-fed and CuD-fed mice under RA. However, in IH exposure, CuD-fed mice showed more pronounced hepatic steatosis, liver injury, and oxidative stress than CuA-fed mice. IH induced copper accumulation in the brain and heart and exacerbated hepatic copper deficiency and secondary iron deposition. In vitro, CuD-treated cells with IH exposure showed elevated levels of lipid accumulation, oxidative stress, and ferroptosis susceptibility. Proteomic analysis identified 360 upregulated and 359 downregulated differentially expressed proteins between CuA and CuD groups under IH; these proteins were mainly enriched in citrate cycle, oxidative phosphorylation, fatty acid metabolism, the peroxisome proliferator-activated receptor (PPAR)α pathway, and ferroptosis. In IH exposure, CuD significantly upregulated the ferroptosis-promoting factor arachidonyl-CoA synthetase long chain family member (ACSL)4. ACSL4 knockdown markedly eliminated CuD-induced ferroptosis and lipid accumulation in IH exposure. In conculsion, IH can lead to reduced hepatic copper reserves and secondary iron deposition, thereby inducing ferroptosis and subsequent MAFLD progression. Insufficient dietary copper may worsen IH-associated MAFLD.

Effectiveness of edoxaban in portal vein thrombosis associated with liver cirrhosis

Portal vein thrombosis (PVT) worsens the long-term prognosis of patients with cirrhosis; however, the optimal treatment remains to be determined. Reports on the efficacy of direct oral anticoagulants are increasing, and further evidence is needed. Therefore, we investigated the effectiveness of treatment with edoxaban in patients with PVT. We retrospectively reviewed the outcomes of edoxaban and warfarin as antithrombotic therapies for PVT. The median overall survival time was 4.2 years in patients with PVT, with a 1-year survival rate of 70.7% and a 5-year survival rate of 47.9%. The leading cause of death was hepatocellular carcinoma. The overall response rate for thrombolysis in the edoxaban group was 76.7% compared to 29.4% in the warfarin group, and edoxaban significantly improved PVT compared to warfarin. In addition, edoxaban provided long-term improvement of PVT. Warfarin, on the other hand, was temporarily effective but did not provide long-term benefits. The Child–Pugh and albumin-bilirubin scores did not change after edoxaban or warfarin use. No deaths occurred due to adverse events associated with edoxaban or warfarin. Edoxaban as a single agent can achieve long-term recanalization without compromising the hepatic reserves. Edoxaban is easy to initiate, even in an outpatient setting, and could become a major therapeutic agent for the treatment of PVT.

Effect of digestible protein on intermediate metabolism, hepatic enzyme activities, energy reserves, and growth performance of pacu (Piaractus mesopotamicus) in the finishing growth phase.

This study investigated the effect of different levels of digestible protein (DP) on blood metabolites, hepatic enzyme activity of glycolysis and amino acid metabolism, energy reserves, and the production characteristics of pacu (Piaractus mesopotamicus) during the finishing growth phase. Six semi purified and isoenergetic diets, containing 16.3, 20.1, 23.8, 27.2, 31.5, and 34.8% of balanced DP, provided with essential amino acid balance, were hand-fed to pacu (1100.0 ± 10.3 g, initial weight) three times daily for 7 weeks. The experiment consisted of six treatments, with three randomly arranged replicates (tanks) per treatment. The data obtained from this experiment were analyzed by one-way analysis of variance (ANOVA), and significant differences (p < 0.05) between treatments were determined using Tukey's test. Blood metabolites, except serum ammonia and the hepatic enzymes activities of glycolysis and amino acid metabolism, except hexokinase activity were affected (p < 0.05) by balanced DP. The energy reserve indices, except hepatic total lipid content, were also found associated (p < 0.05) with balanced DP. The test diets significantly (p < 0.05) affected growth performance parameters. Higher dietary proteins led to a greater energy uptake by fish from the protein in feed. Overall, fish fed the intermediate level (23.8%) of balanced DP with digestible energy of 17.95 MJ kg-1 showed better production traits and physio-biochemical health markers. This information could help nutritionists and farmers to develop nutritionally balanced and economically and environmentally sustainable aquafeed for promoting healthy and sustainable production of pacu in intensive culture systems.

Pediatric Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is characterized by an acute hepatic insult happening in a patient with underlying cirrhosis with compromised hepatic reserve leading to development of systemic inflammation, sepsis, and organ failure resulting in poor outcome in majority. While Asia Pacific Association for Study of Liver Diseases (APASL) emphasizes on early diagnosis before development of organ failure, European Association for Study of Liver Diseases (EASL) mandates the presence of organ failures to define ACLF. There is a lack of consensus definition of pediatric ACLF although recent APASL guidelines have tried to address the issue. While Wilson disease (WD) and autoimmune hepatitis (AIH) are the most common cause of underlying cirrhosis in children, acute viral hepatitis and flares of WD and AIH are the commonest acute precipitating events. Poor outcomes [death and liver transplantation (LT)] ranging from 19 to 59% have been reported. Prognosis in pediatric ACLF is usually better than that in adults due to greater proportion of treatable etiologies, lesser organ failures, comorbidities and better hepatic reserves. APASL ACLF Research Consortium (AARC) score more than or equal to 11 is predictive of poor 28-90 d mortality. Treatment of pediatric ACLF relies mainly on prompt diagnosis and medical management of a potentially treatable etiology of underlying cirrhosis. Bridging therapies, especially high volume plasma exchange can be initiated early as a bridge to LT or native liver recovery. Those with no improvement in 4-7 d should undergo LT before development of sepsis or multi-organ failure.

O14 Hepatic energy reserves and carnitine palmitoyltransferase activity in grazing dairy cows of two pasture-based systems during lactation

O14 Hepatic energy reserves and carnitine palmitoyltransferase activity in grazing dairy cows of two pasture-based systems during lactation

Disturbances to energy metabolism in juvenile lake sturgeon (Acipenser fulvescens) following exposure to niclosamide

Since the 1960s, invasive sea lamprey (Petromyzon marinus) populations in the Laurentian Great Lakes have been controlled by applying two chemicals, 3-trifluoromethyl-4-nitrophenol (TFM) and 2’,5-dichloro-4’-nitrosalicylanilide (niclosamide, aka. Bayluscide®), to streams infested with larval sea lamprey. These “lampricide” applications primarily rely on TFM, and are often combined with 1–2% niclosamide, which increases treatment effectiveness. Niclosamide is also used alone to treat lentic habitats and in rivers with high discharge. However, little is known about niclosamide’s possible adverse physiological effects on non-target organisms. Of particular concern is the lake sturgeon (Acipenser fulvescens), which is threatened throughout the Great Lakes basin where its habitat often overlaps with larval lamprey. Because niclosamide is believed to impair ATP production by uncoupling oxidative phosphorylation, we determined how it altered metabolic processes and acid-base balance in young-of-the-year (YOY) lake sturgeon exposed to their 9-h LC50 of niclosamide (0.11 mg L-1) for 9 h. Exposure to niclosamide led to decreased brain ATP and glucose reserves, and increased lactate, with no effect on brain glycogen. In contrast, substantial (60%) reductions in glycogen were observed in liver, suggesting that hepatic glycogen reserves were mobilized to meet the brain’s glucose requirements when ATP supply was impaired during niclosamide exposure. Disturbances in carcass included reduced phosphocreatine (65–70%), 2- and 4-fold increases in pyruvate and lactate, and a slight metabolic acidosis, characterized by a 0.1 unit decrease in intracellular pH (pHi). Each of these disturbances were corrected within 24 h following depuration in clean (niclosamide-free) water. We conclude that if lake sturgeon survive exposure to niclosamide, they are able to rapidly replenish their energy stores (glycogen, ATP, phosphocreatine) and correct any corresponding metabolic disturbances within 24 h.

Correlation of Clinicopathological Profile, Prognostic Factors, and Survival Outcomes with Baseline Alfa-Fetoprotein Levels in Patients With Hepatocellular Carcinoma: A Biomarker that is Bruised but Not Broken

The role of Alfa-fetoprotein (AFP) in the management of hepatocellular carcinoma (HCC) is still debated, with differences in recommendations between international guidelines. We analyzed the relationship of the clinicopathological profile, prognostic features, and survival outcomes with baseline serum AFP levels in patients with HCC. Retrospective analysis of a prospectively accrued dataset of consecutive HCC patients was done. 508 treatment naive patients were included in the analysis. AFP at presentation was normal (<10ng/ml) in 18% patients. Patients with very high AFP (>400ng/ml) had poor hepatic reserves (higher mean serum bilirubin, AST, ALT, INR, and lower mean albumin) and advanced disease at presentation (higher incidence of extrahepatic metastasis, and less proportion of patients with well-differentiated tumors). AFP >400ng/ml was an independent predictor for presence of portal vein tumor thrombosis (PVTT) (OR, 4.08; 95% CI, 2.34-7.12; P<0.001), higher tumor size (OR, 2.19; 95% CI, 1.36-3.54, P= 0.001) and advanced BCLC stage (OR, 4.19; 95% CI, 2.51-7.03; P<0.001). Two-third of patients with small HCC (MTD <3cm) and more than half with early-stage HCC (BCLC stage 0/A) had elevated AFP levels. No significant relationship was seen between overall survival (OS) and baseline AFP in patients who underwent surgery, but median OS in patients subjected to nonsurgical therapies was 19.4,10.5 and 5.7 months in patients having AFP <10ng/ml, 10-400ng/ml and >400ng/ml respectively (P= 0.003). AFP >400ng/ml was an independent predictor of survival in patients receiving any form of therapy (HR=2.23; 95% CI=1.19-4.18, P= 0.012). AFP as a biomarker still has a significant role to play in the management of HCC patients and is here to stay till the search for an ideal biomarker in HCC is over.

Short‐term metabolic responses of gilthead seabream,Sparus aurata, fed diets with different protein and protein: Energy levels

The present study aimed to evaluate, in gilthead sea bream, the effect of dietary protein:energy (P/E) ratio and non-protein energy (NPE) source on the post-prandial profile of plasmatic parameters, hepatic energy reserves, enzymatic activities of digestive enzymes and hepatic key enzymes activities of the glycolytic (HK and GK), lipogenic (G6PDH and FAS), gluconeogenic (FBPase) and amino acid (GDH, AST and ALT) metabolic pathways. Fish (44 ± 0.05 g) were fed for 34 days four diets with high (HP) or low (LP) P/E ratios and lipid (L) or starch (S) as NPE source (diets HPL, HPS, LPL and LPS, respectively). No differences in growth performance were observed between groups. However, FI was lower, and FE was higher in fish fed the HPS diet than in other groups. Plasma triglycerides and glycaemia were affected by diet composition. Hepatic glycogen and lipid content of fish fed the HPL diet were lower than other groups at different post-prandial times. Digestive enzymes peaked between 6 and 12 h after feeding. HK and GK activities peaked at 6 h after feeding and followed the amylase activity peak. Glycolysis and lipogenesis enzyme activities were higher in fish fed the starch than lipid diets. Gluconeogenesis enzyme activity was high, and amino acid catabolism enzyme activity was lower in fish fed the LP than HP diets. In conclusion, dietary NPE sources and P/E ratio affected the metabolic responses in gilthead sea bream; overall, NPE sources affected carbohydrate metabolism and lipogenesis, whereas P/E ratio mainly affected gluconeogenesis and amino acid catabolism.

Patterns of energetic substrate modifications in response to feeding in boas, Boa constrictor (Serpentes, Boidae)

Ambush-foraging snakes that ingest large meals might undergo several months without eating when they use the internal reserves to support the energetic costs of living. Then, morphological and physiological processes might be orchestrated during the transition from fasting to the postprandial period to rapidly use the energetic stores while the metabolic rate is elevated in response to food intake. To understand the patterns of substrates deposition after feeding, we accessed the morphological and biochemical response in Boa constrictor snakes after two months of fasting and six days after feeding. We followed the plasma levels of glucose, total proteins, and total lipids, and we performed the stereological ultrastructural analysis of the liver and the proximal region of the intestine to quantify glycogen granules and lipid droplets. In the same tissues and stomach, we measured the activity of the enzyme fructose-1,6-biphosphatase (FBPase1) involved in the gluconeogenic pathway, and we measured pyruvate kinase (PK) and lactate dehydrogenase (LDH) enzymatic activities involved in the anaerobic pathway in the liver. Briefly, our results indicated an increase in boas' plasma glucose one day after meal intake compared to unfed snakes. The hepatic glycogen reserves were continuously restored within days after feeding. Also, the enzymes involved in the energetic pathways increased activity six days after feeding in the liver. These findings suggest a quick restoring pattern of energetic stores during the postprandial period.

A nutritional strategy to promote gilthead seabream performance under low temperatures

Gilthead seabream (Sparus aurata) is vulnerable to low water temperature, which may occur in the Southern Europe and Mediterranean region during Winter. Fish are poikilothermic animals, therefore feed intake, digestion, metabolism and ultimately growth are affected by water temperature. This study aimed to evaluate growth performance, feed utilisation, nutrient apparent digestibility, and nitrogen losses to the environment in gilthead seabream juveniles reared under low temperature (~13 °C). Three isolipid and isoenergetic diets were formulated: a diet similar to a commercial feed (COM) that contained 44% crude protein and 27.5% fishmeal, and two experimental diets with a lower protein content of 42% (ECO and ECOSup). In both ECO diets fishmeal inclusion was reduced (10% in ECO and 7.5% in ECOSup diet) and 15% poultry meal was included. Additionally, the ECOSup diet was supplemented with a mix of feed additives intended to promote fish growth performance and feed intake. The ECO diets presented lower production costs than the COM diet, whilst incorporating more sustainable ingredients. Gilthead seabream juveniles (±154.5 g initial body weight) were randomly assigned to triplicate tanks and fed the diets for 84 days. Fish fed the ECOSup diet attained a similar final body weight than fish fed the COM diet, significantly higher than fish fed the ECO diet. ECOSup fed fish presented significantly higher hepatosomatic index than COM fed fish, most likely due to higher hepatic glycogen reserves. The viscerosomatic index of ECOSup fed fish were significantly lower compared to COM fed fish, which is a positive achievement from a consumer's point of view. ECOSup diet exhibited similar nutrient digestibility than the COM diet. Moreover, feeding fish with the ECO diets resulted in lower faecal nitrogen losses when compared to COM fed fish. The results suggest that feeding gilthead seabream with an eco-friendly diet with a mix of feed additives such as the ECOSup diet, promoted growth and minimised nitrogen losses to the environment. Nutritional strategies that ultimately promote feed intake and diet utilisation are valuable tools that may help conditioning fish to sustain growth even under low temperatures.

Effects of feed restriction on growth performance, lipid mobilization, and gene expression in rose spotted snapper (Lutjanus guttatus)

The effects of feed deprivation were evaluated for 1week and 2weeks in Lutjanus guttatus juveniles. A significant reduction in body mass was observed in both feed deprivation schemes, as well as in hepatosomatic, viscerosomatic and mesenteric fat indexes. The composition of fasted fish was characterized by a decrease in lipid content; the liver displayed an intense reduction of lipid reserves in both fasted groups, and increased expression of the lysosomal acid lipase. 1week after re-feeding, both experimental groups showed an increase in specific growth rate, feed intake and feed conversion ratio. A recovery in hepatic lipid reserves was observed, and the expression of the lysosomal acid lipase decreased, although lipid content in both groups was still significantly lower than in control groups. Hepatic expression of the growth hormone receptor decreased after fasting, and remained low even after the fish were fed, whereas the expression of insulin-like growth factor 1 and 2 increased after fasting and decreased in both groups when fish were fed again. Altogether, these results showed a partial compensatory growth response in L. guttatus juveniles after fasting, with enhanced growth rates and improved feed efficiency. Fish used stored lipid reserves as the main energy source, and the expression of growth-related and lipid mobilization marker genes in the liver showed similar patterns in both fasting schemes. Based on the results, we suggest as much as 1-week fasting intervals during grow-out programmes to reduce visceral fat and increase growth rate in this species.

Mango pulp meal in diets for Nile tilapia (Oreochromis niloticus): Digestibility, Growth performance, Biochemical analysis, Digestive enzyme activity, hematological variables

ABSTRACT The objective of this study was to evaluate the potential of mango pulp meal (MPM) as an ingredient for extruded diets for Nile tilapia juveniles. In the first trial, the digestibility of energy, dry matter, crude protein, and amino acids was determined, using 80 juveniles (average weight 25.00 ± 0.50 g), fed with a reference diet and a test diet containing the proportion of 70% of the reference diet and 30% of the MPM. Chromium oxide (Cr2O6) was used as an digestibility indicator and feces were collected using the Adapted Guelph System. The second assay assessed the growth performance; biochemical analysis; digestive enzyme activity; hematological variables for 300 juveniles fish (average weight 26.66 ± 0.17 g), fed for 45 days with balanced diets containing 0 (control), 40, 80, 120, and 160 g of MPM per kg-1. The dry matter, crude protein, and crude energy apparent digestibility coefficients of MPM were 39.26, 50.18, and 44.5%, respectively. The growth performance of the animals was negatively impacted by the MPM, however the hematological parameters and plasma concentrations of albumin, total proteins and cholesterol were not altered. However, the increase on hepatic glycogen reserves, glycemia, and alanine aminotransferase plasmatic enzyme activity demonstrated that MPM diet inclusion promoted oxidative metabolism conditions that could cause hepatocellular damage and affect fish health, if fed for long periods or at higher levels of MPM than analyzed in this study.

Characterizing the composition, metabolism and physiological functions of the fatty liver in Rana omeimontis tadpoles

BackgroundFat storage is required for the life cycle of many organisms. The primary fat depot for most vertebrates is white adipose tissue. However, in primitive vertebrates (e.g., agnathan group and elasmobranchs), the liver is usually responsible for fat storage. Among the vertebrates, amphibians have a unique status, as their larvae live in the water and exhibit some primitive traits that are similar to fish. Although it has been recognized that adult frogs use their abdominal white adipose tissue as a primary fat depot, how tadpoles store their fat is still inconclusive. The metabolic traits and physiological functions of primitive fat depots may have wide-ranging implications on the pathology of abnormal lipid deposition in mammals and the evolution of fat storage.ResultsRana omeimontis tadpoles used their liver as the primary fat depot. In sufficiently fed tadpoles at stage 30–31, the hepatosomatic index (HSI) reached up to 7%, and triglycerides (TG) accounted for 15% of liver weight. Their liver resembled white adipose tissue in histological morphology, characterized by polygonal hepatocytes filled with fat. Their liver metabolic composition was unique, characterized by the dominance of maltotriose, arachidonic acid and dipeptides in soluble carbohydrates, free fatty acids and amino acids. Hepatic fat was the major metabolic fuel of fasted R. omeimontis tadpoles, which had similar reserve mobilization and allocation patterns as mammals. From a developmental perspective, hepatic fat was important to fuel late metamorphic climax. Interestingly, starvation induced accelerated metamorphosis in tadpoles with high HSI (4.96 ± 0.21%). However, this phenomenon was not observed in tadpoles with low HSI (2.71 ± 0.16%), even though they had similar initial body weight and developmental stage. Hepatic fat abundance was the most prominent difference between the two groups.ConclusionTo the best of our knowledge, this is the first report that liver can be the primary fat depot in vertebrates with higher evolutionary status than bony fish. The unique hepatic histological and metabolic traits likely either guard their liver against lipotoxicity or make their hepatocytes adapt to fat accumulation. This fatty liver could be a primitive counterpart of mammalian white adipose tissue (WAT). In addition, our study showed that the hepatic reserves of tadpoles, especially TG content, may provide body condition signals to modulate metamorphosis.

240P - Hepatic reserve and the other conditions for regorafenib as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib in Japanese practical setting

Background: In RESORCE trial, which revealed that regorafenib has improved survival of the patients with advanced hepatocellular carcinoma (aHCC) after sorafenib, only patients with preserved hepatic reserve were included. We investigated change of hepatic reserve and the other conditions for proven benefit of regorafenib after sorafenib treatment in Japanese practical setting. Methods: We retrospectively reviewed change of Child-Pugh score and the other conditions at commencement and cessation of sorafenib, and evaluated the effect of change in Child-Pugh scores on second line treatment and outcomes in patients with aHCC. Results: Of the 120 patients whose aHCC were treated with sorafenib, 87 patients (73%) and 67 patients (56%) had sufficient hepatic reserve that is Child-Pugh A. After median 2.4 months of sorafenib treatment, hepatic reserve remained Child-Pugh A in 57 of 87 (66%) patients with Child-Pugh A before sorafenib, and it improved to Child-Pugh A in 10 of 33 (33%) patients with Child-Pugh B before sorafenib. At cessation of sorafenib treatment, only 50 patients (42%) fulfilled key inclusion criteria of RESORCE trial (Child-Pugh A, ECOG PS 0 or 1, tumor progression on imaging and administration of ≥ 400mg of sorafenib for at least 20 of the last 28 days before discontinuation; 67 patients (56%), 103 patients (86%), 90 patients (75%), and 86 patients (72%) fulfilled each criterion, respectively). Multivariate analysis revealed that only Child-Pugh score of 5 before sorafenib was contributing factor to Child-Pugh A at cessation of sorafenib. Significantly more patients with Child-Pugh A at cessation of sorafenib treated by any subsequent therapies compared to patients with Child-Pugh B (86.6 vs 52.8%; P < 0.001) and had better outcome (median overall survival of 13.7 vs 7.1 months; P = 0.004). Conclusions: Sorafenib treatment can deteriorate hepatic reserves even if the patients have sufficient hepatic reserve before treatment. Maintaining hepatic reserve during sorafenib treatment should be taken care because it contributes to treatment of subsequent therapies such as regorafenib treatment and longer survival of patients with aHCC. Legal entity responsible for the study: Kanazawa University Hospital Funding: None Disclosure: All authors have declared no conflicts of interest.

Survival benefit of TACE combined with sorafenib for hepatocellular carcinoma patients with portal vein tumor thrombus

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignant tumor and the world’s fifth most common tumor. Portal vein tumor thrombosis (PVTT) have been appeared about 10–40% for HCC patients (1,2). PVTT predicted a dismal prognosis, because they promoted HCC recurrence and metastasis, impaired hepatic reserves, raised portal vein pressure, and reduced portal vein flow. The median survival time (MST) of HCC and PVTT patients is obviously decreased compared to those without PVTT. According to the invading location in portal vein of the PVTT, the studies from our group proposed “Cheng’s classification” to divided the PVTT into four types (type I, being segmental/sectoral branches of portal vein; type II, being left and/or right portal vein; type III, being main portal vein trunk, and type IV, being superior mesenteric vein) (3,4). According to the guidelines from Barcelona Clinic Liver Cancer (BCLC), HCC with PVTT was classified as advanced HCC (BCLC stage C). They recommended sorafenib as the standard treatments for patients with advanced HCC. However, some studies have shown that some treatment modalities like transarterial chemoembolization (TACE), radiotherapy (RT), transarterial radioembolization (TARE), and resection-based multimodal treatments in some selected HCC and PVTT patients may prefer better outcomes than sorafenib (5-7). Our comments were responded to “editorial on combination treatment beyond sorafenib alone for HCC with portal vein tumor thrombosis”, and indicated that the new advances treatments were applied for HCC patients with PVTT.

In situ evaluation of the toxicological impact of a wastewater effluent on the fish Prochilodus lineatus: biochemical and histological assessment

Sewage effluents are the most important source of emergent pollutants in the aquatic environment. In the present study the toxicological impact of an untreated sewage effluent on the Prochilodus lineatus fish was assessed under field conditions using a caging experiment. The biomarkers which were measured here involved oxidative stress markers, hepatic function parameters, neurotoxicity indicators, energy reserves, histological alterations and brain cell proliferation. In addition, water quality parameters including the occurrence of some human pharmaceuticals were measured. Juveniles of P. lineatus were caged for 15days at three sites: the effluent site, and 2km upstream and downstream from the effluent discharge. Caffeine, atenolol, carbamazepine, enalapril and sildenafil were detected in water river samples. The increased activation of caspase-3 and the decreased cell proliferation in the diencephalon showed that the brain of fish caged at the effluent was affected. These fish also displayed a rise in hepatic transaminase activity, and oxidative stress in liver and gills which was evidenced by an increased lipid peroxidation and activation of antioxidant enzymes. At tissue level, increased glycogen and decreased lipid contents in liver as well as the highest indexes of hepatic lesions were also observed in the fish caged at the effluent. Both biochemical and histopathological findings demonstrated that effects were more severe on the liver of such fish than on their gills. The in situ exposure method carried out in our study makes it possible to observe the real effects of the sewage effluent on fish. Furthermore, our results also provide a better understanding of the harmful effects of wastewater effluents on the aquatic wildlife.

Acetazolamide Use in Severe Chronic Obstructive Pulmonary Disease. Pros and Cons.

Acetazolamide is a carbonic anhydrase (CA) inhibitor sometimes used as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) with the goal of improving oxygenation, reducing carbon dioxide retention, and aiding liberation from mechanical ventilation and/or attempting to correct a metabolic alkalosis. However, the net effect of CA inhibition is multifactorial and complex, because CA is inhibited in many tissues that may negatively affect the patient with lung disease. The full impact of acetazolamide and other CA inhibitors depends critically on dosing, age, and pulmonary, renal, hepatic, hematological, and respiratory muscle function and reserves. This review examines the literature and indications for acetazolamide use in patients with COPD dating back to its initial release 6 decades ago. There are very few studies specifically designed to address the population with severe COPD, as such patients were frequently excluded from trials. We therefore discuss the complexity of CA inhibition and its potential benefits and dangers and describe ways in which the pathophysiology of patients with severe COPD puts them at considerable risk for serious adverse consequences. We offer guidance on the careful and rational use of acetazolamide in patients with respiratory disorders.

Impact of abiotic factors on some biological indices of Cyprinus carpio (L., 1758) in Ghrib dam lake, (Algeria)

AbstractThis study was conducted with a sample of 733 Cyprinus carpio collected between May 2013 and February 2016 from the ecosystem lake in the Ghrib dam which is eutrophic. Cyprinus carpio in this dam is characterized by a single fractional spawning that begins in the spring and ends in the late summer. The distributions of the viscerosomatic and gonadosomatic indices decrease between the spring and summer seasons. These periods correspond to the spawning period and the biological break of this species. They progressively increase between autumn and winter when the biological activity of the species returns. The hepatosomatic index progressively decreases between the spring and the summer when the hepatic reserves are used for reproduction. The repletion index shows that the trophic activity of C. carpio is intense in the spring. The condition factor varies between 1.1 and 1.35. The evolution of the biological indices of both sexes is well stressed in well‐defined periods according to the seasons. The values are weak for males and high for females. The redundancy analysis allows the characterization of the influence of the physico‐chemical parameters of the dam water, especially the role of the nutritious elements, in the biological seasonal cycle of C. carpio.

Temperature during the last week of incubation. III. Effects on chicken embryo physiology

We investigated effects of eggshell temperature (EST) of 35.6, 36.7, 37.8, or 38.9°C applied from d of incubation (E) 15, E17, or E19 onward on chicken embryo physiology. A total of 2,850 first-grade eggs of a 43-week-old Ross 308 broiler breeder flock were incubated at an EST of 37.8°C until E15. From E15, E17, or E19 onward, eggs were incubated at an EST of 35.6, 36.7, 37.8, or 38.9°C. Plasma glucose, uric acid, and lactate concentrations, and hepatic glycogen amount and concentration were measured at E15, E17, E19, internal pipping (IP), external pipping (EP), and hatch.An EST of 38.9°C applied from E15 onward decreased the amount of hepatic glycogen from E19 to IP and resulted in a lower glycogen amount at IP compared to all other EST. At EP, when oxygen (O2) becomes largely available, an EST of 38.9°C resulted in a higher glycogen amount and concentration compared to IP, which suggests that plasma glucose between IP and EP might be used for building up hepatic glycogen reserves. However, hepatic glycogen levels remained considerably lower at IP, EP, and hatch at an EST of 38.9°C, compared to an EST of 35.6 and 36.7°C.Opposite to an EST of 38.9°C, from IP onward, an EST of 35.6°C resulted in a higher glycogen amount and concentration compared to all other EST, which might be caused by the higher O2 availability relative to the lower metabolic rate, which provided time to build up glycogen stores from excessive glucose. A higher availability of hepatic glycogen might contribute to an improved physiological status of the broiler chicken embryo toward hatch. Hepatic gluconeogenesis is crucial for developing embryos, as glucose is the major energy source from IP until hatch. At hatch, no effect of EST was found for glucose, uric acid, or lactate.Results of this study emphasize that EST of 35.6 and 36.7°C from E15 onward appear to be beneficial for chicken embryo physiology.