Hepatic Side Research Articles

The antihyperlipidemic effects of coenzyme Q10 and gemfibrozil on hyperlipidemic male rats: a comparative study

Dyslipidemia is considered as the most common risk factor for cardiovascular diseases, cerebrovascular diseases, and fatty liver disease. The available therapy aimed to decrease lipid profile and reduced long-term risk which do require lifelong therapy, hence adverse effects are suggestive. The goal of the present study is to compare the anti¬hyperlipidemic influence and hepatic side effects of CoQ10 and gemfibrozil in the hyperlipidemic male rats model. Twenty-five albino rats were divided into 5 groups: group 1(normal group), group 2 (olive oil group), group 3(hyperlipidemia-induced group) group 4 (CoQ10-treated group), and group 5 (gemfibrozil-treated group). Induction of hyperlipidemia lasts for 90 days and treatment lasts for 30 days. Serum liver enzyme analysis and liver histological study conducted to demonstrate the safety profile of the treatment agents. Analysis of the data revealed that the lipid profile parameters (except HDL) and liver enzymes were significantly (p< 0.001) higher in the hyperlipidemic group (Group 3) compared to either the control group (Group 1) or olive oil group. Using CoQ10 (Group 4) and gemfibrozil (Group 5) has revealed that the lipid parameters and liver enzymes were significantly (p<0.001) lower compared to the hyperlipidemic group (Group 3). Compared to control group, liver showed congestion of sinusoids, severe necrosis of hepatocytes, vacuolar degradation, and infiltration of inflammatory cells, these effects reversed in presence of CoQ10. Compared to gemfibrozil, CoQ10 provides safer and equally effective option for treatment of dyslipidemia represented by improved lipid parameters and liver enzymes alongside protected hepatic architecture.

Prognostic factors for resected cases with gallbladder carcinoma: a systematic review and meta-analysis.

Current meta-analysis was performed to systematically evaluate the potential prognostic factors for overall survival among resected cases with gallbladder carcinoma. PubMed, EMBASE, and the Cochrane Library were systematically retrieved and hazard ratio (HR) and its 95% confidence interval were directly extracted from the original study or roughly estimated via Tierney's method. Standard Parmar modifications were used to determine pooled HRs. A total of 36 studies with 11502 cases were identified. Pooled results of univariate analyses indicated that advanced age (HR=1.02, P =0.00020), concurrent gallstone disease (HR=1.22, P =0.00200), elevated preoperative CA199 level (HR=1.93, P <0.00001), advanced T stage (HR=3.09, P <0.00001), lymph node metastasis (HR=2.78, P <0.00001), peri-neural invasion (HR=2.20, P <0.00001), lymph-vascular invasion (HR=2.37, P <0.00001), vascular invasion (HR=2.28, P <0.00001), poorly differentiated tumor (HR=3.22, P <0.00001), hepatic side tumor (HR=1.85, P <0.00001), proximal tumor (neck/cystic duct) (HR=1.78, P <0.00001), combined bile duct resection (HR=1.45, P <0.00001), and positive surgical margin (HR=2.90, P <0.00001) were well-established prognostic factors. Pathological subtypes ( P =0.53000) and postoperative adjuvant chemotherapy ( P =0.70000) were not prognostic factors. Pooled results of multivariate analyses indicated that age, gallstone disease, preoperative CA199, T stage, lymph node metastasis, peri-neural invasion, lymph-vascular invasion, tumor differentiation status, tumor location (peritoneal side vs hepatic side), surgical margin, combined bile duct resection, and postoperative adjuvant chemotherapy were independent prognostic factors. Various prognostic factors have been identified beyond the 8th AJCC staging system. By incorporating these factors into a prognostic model, a more individualized prognostication and treatment regime would be developed. Upcoming multinational studies are required for the further refine and validation.

Laparoscopic Portal Vein Ligation and Embolization During First-Stage Hepatectomy for Initially Unresectable Colorectal Liver Metastases.

Two-stage hepatectomy (TSH) is the only treatment for the patients with multiple bilobar colorectal liver metastases (CRMs) who are not candidates for one-step hepatectomy because of insufficient future remnant liver volume and/or impaired liver function.1-5 Although laparoscopic approaches have been introduced for TSH,6-8 the postoperative morbidity and mortality remains high because of the technical difficulties during second-stage hepatectomy.9,10 The authors present a video of laparoscopic TSH with portal vein (PV) ligation and embolization, which minimizes adhesions and PV thrombosis risk in the remnant liver, thereby facilitating second-stage hepatectomy. Three patients with initially unresectable bilateral CRMs received a median of chemotherapy 12 cycles, followed by conversion TSH. After right PV ligation, laproscopic PV embolization was performed by injection of 100% ethanol into the hepatic side of the right PV using a 23-gauge winged needle. After PV embolization, a spray adhesion barrier (AdSpray, Terumo, Tokyo, Japan)11 was applied. During the first stage of hepatectomy, two patients underwent simultaneous laparoscopic colorectal resection (left hemicolectomy and high anterior resection). In the initial hepatectomy, two patients underwent two limited hepatectomies each, and one patient underwent six hepatectomies in the left lobe. After hepatectomy, all the patients underwent right PV embolization. During the second stage, two patients underwent open extended right hepatectomy (right adrenalectomy was performed because of adrenal invasion in one patient), and one patient underwent laparoscopic extended right hepatectomy. No postoperative complications occurred in the six surgeries. Laparoscopic TSH with PV embolization is recommended for safe completion of the second hepatectomy.

Morphometric, biochemical and histopathological effects of sofosbuvir (sovaldi) on testes of adult male albino rats

ABSTRACT Sofosbuvir treatment regimens for chronic HCV infection have recently been linked to extra hepatic side effects. This study aimed to show how sofosbuvir affected the adult male albino rat testis. Forty adult male albino rats were used. The rats were equally split into two main groups (I and II), then each group subdivided into two subgroups (A and B). Each rat in group I (control) received 0.5 ml of distilled water every day for four weeks. Each rat in group II (sofosbuvir-treated) received 0.5 ml of distilled water containing 7.2 mg of sofosbuvir every day for four weeks. After four weeks (subgroups IA and IIA) and eight weeks (subgroups IB and IIB) of treatment, the rats were sacrificed. Histological, biochemical, and morphometric studies on the testes were conducted. The data were analyzed. Examination of testes of sovaldi treated group revealed histopathological changes. Biochemical and morphometric analysis showed reduced levels of reduced glutathione and seminiferous tubule epithelial height respectively. Following a 4-week drug withdrawal period, the testes only partially recovered. We concluded that sofosbuvir induced deteriorating changes in the adult male albino rats’ testes. These changes were proved by histological and biochemical studies. These changes were incompletely reversible after cession of treatment. Researches investigating the effect of adding drugs that have antioxidant properties during sofosbuvir therapy are recommended.

The Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Receiving Tocilizumab: A Systematic Review and Meta-Analysis.

Tocilizumab has demonstrated optimal efficacy and safety in patients with rheumatoid arthritis (RA) from clinical trials. However, the risk of hepatitis B virus reactivation (HBVr) in these patients remains uncertain because patients with underlying HBV have been excluded in phase III studies. Systematical reviews were conducted on PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to 21 February 2023. Random-effects meta-analysis was performed to calculate the pooled incidence of HBV reactivation. We included 0 clinical trials and 11 observational studies with a total of 25 HBsAg+ and 322 HBsAg-/anti-HBc+ RA patients. Among the HBsAg+ patients without antiviral prophylaxis, the pooled rate was 69.4% (95% CI, 32.9-91.3), with a median time of 4 months (range, 1-8 months) from tocilizumab initiated. Half of these patients with HBVr experienced hepatitis flare-up but no deaths. HBVr was eliminated with prophylaxis in this population. Among HBsAg-/anti-HBc+ patients, the pooled incidence of reactivation was 3.3% (95% CI, 1.6-6.7), with a median time of 10 months (range, 2-43 months) from tocilizumab initiated. HBVr was not associated with hepatitis flare-up and death. HBsAg-/anti-HBc+ patients without anti-HBs antibodies had a significantly higher risk of HBVr (Odds ratio, 12.20; 95% CI, 1.16-128.06). This systematic review indicated that the risk of HBVr in RA patients with anti-HBs-, HBsAg+, or HBsAg-/anti-HBc+ cannot be ignored but may be avoided. Clinicians should consider implementing appropriate antiviral prophylaxis and monitoring policies for RA patients to avoid unnecessary hepatic side effects from tocilizumab treatment.

Cardiac and hepatic side effects of fluoxetine in male and female adolescent rats.

Fluoxetine (FLX) is widely prescribed as an antidepressant medicine in the juvenile population. Although some adverse effects of FLX have been reported in adults, the present study aimed to investigate the side effects of FLX treatment during adolescence on the cardiac and hepatic systems. Male and female rats were gavaged with FLX (5mg/kg/day) on postnatal days (PND) 21 to PND 60. Following treatment, blood samples were collected and hepatic enzymes were evaluated. The specimens of the liver and heart of animals were subjected to histopathological assessment. Fluoxetine significantly raised serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in males, whereas the aspartate aminotransferase (AST) level increased in both male and female animals. In the histopathological study, hepatic plates were more seriously affected, and the sinusoids were irregular in adolescent male rats. Degenerative changes were observed especially in the first and second hepatic zones of FLX-treated male rats. Signs of inflammation and accumulation of lymphoid groups were frequently observed in the portal triad of the hepatic lobules. These alterations were more severe in male livers. Minimum or nearly normal changes were observed in female liver slides. In addition, the histological assessment indicated that treatment with FLX during adolescence also increased the heart's weight and the wall thickness of the right and left ventricles (hypertrophy) in male and especially female animals. Our findings may provide new insights into the cardiac and hepatic adverse effects of FLX.

Chondroitin Sulphate-Chitosan polyelectrolyte complexes for etorocoxib transdermal delivery: in silico, in vitro and in vivo studies

Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects around 1% globally leading to joint inflammation and disability. Etorocoxib (ETR) is a potent COX-2 inhibitor traditionally used orally to alleviate RA induced inflammation, yet it causes hepatic side effects on prolonged use. This study aims for in silico optimization of ETR polyelectrolyte complex (PEC) utilizing chondroitin sulphate (CS) and chitosan (CH) for transdermal delivery to RA-inflamed joints with a synergistic anti-inflammatory action owing to CS. An artificial neural network (ANN) combined with 22 factorial design was used to optimize the PEC formula according to particle size (PS) and entrapment efficiency (%EE) by varying CS and CH concentrations. The optimum ETR PEC was incorporated in a gel and examined for its in vitro release, ex vivo permeation, in vivo inflammatory biomarkers, and histopathological evaluation in rats. The optimized formula (F3) with 0.1 CH% w/w and 0.5 CS %w/w showed a PS of 214.98 ± 17.24 nm, %EE 75.31 ± 1.67%, and enhanced in vitro release profile, ex vivo permeation and in vivo anti-inflammatory effect compared to ETR gel via suppressing the expression of IL-6, TNF-α, and TGF-β pro-inflammatory cytokines as well as the additional anti-inflammatory effect of CS. In conclusion, ETR-PEC gel holds promise as transdermal therapy for managing RA-induced inflammation.

Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.

Antiviral protease inhibitors are peptidomimetic molecules that block the active catalytic center of viral proteases and, thereby, prevent the cleavage of viral polyprotein precursors into maturation. They continue to be a key class of antiviral drugs that can be used either as boosters for other classes of antivirals or as major components of current regimens in therapies for the treatment of infections with human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, sustained/lifelong treatment with the drugs or drugs combined with other substance(s) often leads to severe hepatic side effects such as lipid abnormalities, insulin resistance, and hepatotoxicity. The underlying pathogenic mechanisms are not fully known and are under continuous investigation. This review focuses on the general as well as specific molecular mechanisms of the protease inhibitor-induced hepatotoxicity involving transporter proteins, apolipoprotein B, cytochrome P450 isozymes, insulin-receptor substrate 1, Akt/PKB signaling, lipogenic factors, UDP-glucuronosyltransferase, pregnane X receptor, hepatocyte nuclear factor 4α, reactive oxygen species, inflammatory cytokines, off-target proteases, and small GTPase Rab proteins related to ER-Golgi trafficking, organelle stress, and liver injury. Potential pharmaceutical/therapeutic solutions to antiviral drug-induced hepatic side effects are also discussed.

Traditional Korean Medicine Treatment for Sequelae After Tamoxifen in Breast Cancer Patients: Two Case Reports

Objective: The purpose of this study is to report two cases of breast cancer patients whose side effects after Tamoxifen were treated with traditional Korean medicine.Methods: Two breast cancer patients underwent Tamoxifen after breast-conserving surgery, and both were treated with traditional Korean medicine. Subjective discomfort symptoms were evaluated using the Numerical Rating Scale. Adverse events were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0.Results: After treatment with traditional Korean medicine, the discomfort symptoms that occurred after Tamoxifen, such as osteoarthritis, hot flushes, and cold sweat, all gradually improved. In addition, no hematologic, hepatic, or renal side effects were observed from the traditional Korean medicine treatment.Conclusion: This case study suggests that traditional Korean medicine may contribute to the improvement of side effects caused by Tamoxifen and enhance the quality of life of patients.

Iron Overload Following Hematopoietic Stem Cell Transplantation: Prevalence, Severity, and Management in Children and Adolescents with Malignant and Nonmalignant Diseases

Iron overload (IOL) is a frequently reported complication following hematopoietic stem cell transplantation (HSCT) that has been investigated extensively in the field of hemoglobinopathies but has not been thoroughly characterized after HSCT in pediatric malignancies. Our aim was to assess prevalence, severity, risk factors, and management of IOL, as defined using biochemical (serum ferritin) and radiologic tools (T2*-weighted magnetic resonance imaging [MRI]), in a cohort of pediatric patients who underwent HSCT for either malignant or benign diseases. This monocentric, retrospective, observational study included all the 163 patients alive and in continuous remission at 24 months post-HSCT out of the 219 consecutive children and adolescents who underwent HSCT at our institution between 2012 and 2018, were included in the study. IOL was classified into 4 categories: absent, mild, moderate, and severe. Among the 163 patients, 73% had some degree of IOL (mild in 37%, moderate in 29%, and severe in 7%). Moderate/severe IOL was more frequent among patients diagnosed with a malignant disease versus those with a benign disease (43% versus 19%; P = .0065). Trend lines for serum ferritin showed a "bell-shaped" distribution, with the highest levels recorded during the first 6 months post-HSCT, followed by a spontaneous reduction. Both pre-HSCT (1659 ng/mL versus 617 ng/mL; P < .001) and maximum post-HSCT (2473 ng/mL versus 1591 ng/mL; P < .001) median ferritin levels were statistically higher in the patients with malignancies. Radiologic assessment of IOL confirmed a more severe degree in patients with malignant disorders compared to those with benign disorders (median T2*-MRI, 4.20 msec [interquartile range (IQR), 3.0 to 6.40 msec] versus 7.40 msec [IQR, 4.90 to 11.00 msec]; P = .008). T2* levels were associated with the number of transfusions performed (P = .0006), with a steeper drop in T2* values for the first 20 transfusions and a milder slope for subsequent transfusions. T2* and ferritin values showed a statistically significant negative exponential relationship (P < .0001), although a ferritin level ≥1000 ng/mL showed poor specificity (48%) and low positive predictive value (53%) for discriminating moderate-to-severe IOL from absent-mild IOL as assessed by T2*-MRI, but with high sensitivity (92%) and negative predictive value (91%). In a multivariable model, >20 transfusions (odds ratio [OR], 4.07; 95% confidence interval [CI], 1.61 to 10.68; P = .003) and higher pre-HSCT ferritin level (P < .001) were associated with the risk of developing moderate-to-severe IOL. Use of a sibling donor (OR, .29; 95% CI, .10 to .77; P=.015) and a nonmalignancy (OR, .27; 95% CI, .08 to .82; P=.026) were protective factors. Phlebotomy (66%), low-dose oral chelators (9%), or a combined approach (25%) were started at a median of 12 months after HSCT in 78% of the patients with IOL. Six percent of the patients treated exclusively with phlebotomy (median, 14, significantly higher in patients >40 kg) discontinued phlebotomy owing to poor venous access, lack of compliance, or hypotension, whereas 39% of patients treated with chelators developed mild renal or hepatic side effects that resolved after tapering or discontinuation. Patients with malignancies showed statistically higher pre-HSCT and post-HSCT ferritin levels and lower T2* values. High ferritin level recorded on T2*-MRI showed unsatisfactory diagnostic accuracy in predicting IOL; thus, T2*-MRI should be considered a key tool for confirming IOL after HSCT in patients with an elevated serum ferritin level. IOL treatment is feasible after HSCT.

Doking studije nekih jedinjenja sa pirazolom u aktivnom mestu ciklooksigenaze-2

Whereas nonselective nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen and diclofenac, inhibit both cyclooxygenase-1 and cyclooxigenase-2 enzymes, selective inhibitors target cyclooxygenase-2, which is overexpressed in inflammation, but also in cancer, atherosclerosis, Alzheimer's disease, and Parkinson's disease. Potential cardiovascular and hepatic side effects of cyclooxygenase-2 inhibitors have limited their use. The development of selective and safe cyclooxygenase-2 inhibitors remains a high priority in drug discovery. Based on the structure of previously investigated newly synthesized b-hydroxy-b-arylpropanoic acids, two groups of compounds were designed: analogs in which one of the benzene rings was replaced by a pyrazole, while the carboxyl group was retained, and amides of b-hydroxy-b-arylpropanoic acids with pyrazole. The compounds were docked into the 3D structure of the catalytic site of the enzyme cyclooxygenase-2 using AutoDock Vina 1.2.0. and the obtained interactions were compared with the interactions of celecoxib, a selective inhibitor. The amides had lower binding energies than the designed acids, which makes them attractive target compounds for synthesis and further examination.

Residual cancer is a strong predictor of survival in T3 incidental gallbladder cancer

Background and purposeIndex cholecystectomy is insufficient for curing T3 incidental gallbladder cancer (IGC), and once residual cancer (RC) is found, the prognosis is often poor. The purpose of this study was to investigate the effect of RC on the prognosis and the optimal choice of adjuvant therapy for R0 reresection patients with T3 IGC.MethodsWe retrospectively reviewed data from patients with T3 IGC who underwent radical reresection from January 2013 to December 2018. RC was defined as histologically proven cancer at reresection. Demographics and tumour treatment-related variables were analysed in correlation with RC and survival. Adjuvant (Adj) chemoradiotherapy (CRT) was correlated with overall survival (OS) and disease-free survival (DFS).ResultsOf the 167 patients with IGC who underwent surgery, 102 underwent radical extended resection. Thirty-two (31.4%) RCs were found. Hepatic side tumours (T3h) and both side tumours (T3h + T3p) were associated with the presence of RC. In multivariate analysis, RC and lymph node metastasis were independent prognostic factors for DFS and OS (P < 0.05). RC was associated with a significantly shorter median OS (20 vs. 53 months; P < 0.01) and DFS (11 vs. 40 months; P < 0.001) despite R0 resection. For R0 reresection patients with RC and/or lymph node metastasis, Adj CRT significantly improved OS (P = 0.024).ConclusionResidual cancer and lymphatic metastasis are important factors for the poor prognosis of T3 IGC despite R0 resection, and these patients should actively receive adjuvant therapy.

Green Tea Consumption Is Increasing but There Are Significant Hepatic Side Effects

Herbal medicines including teas and plant extracts have been in use for thousands of years. There are reports of the use of herbal preparations in Egypt, China, India, and Samaria. Many patients consider “natural” herbal teas to be completely free of unwanted side effects. Many herbal products, however, have biological activities that can result in severe hepatic cell toxicity or interact with other herbal products or prescription medications. Their use is increased dramatically. The most common herbal teas and nonmineral natural products are used as self-medication, principally for health improvement. However, these products are potentially dangerous to some individuals. Monitoring for liver injury is an important aspect of drug and herbal safety assessment. When present, herbal-induced liver injury (HILI) may limit the use or result in the discontinuation of these agents. HILI can exhibit with a wide spectrum of clinical and laboratory manifestations, ranging from asymptomatic elevations in aminotransferases to acute liver failure. Most cases of HILI resolve within several weeks after herbal remedy discontinuation. However, some cases can persist as low-level aminotransferase elevations. Our review aims to (1) describe the possible significant discrepancies between the ingredients listed on the label and the actual contents of the preparation; (2) evaluate teas containing multiple plants or herbs which may be adulterated by more toxic herbs, heavy metals, microbials, pharmaceuticals, and medicines; (3) describe pathophysiologic events in herbal tea-induced hepatotoxicity; and (4) discuss the key elements required for attributing the consumption of tea to the induction of liver injury. The widespread use of mixed heterogeneous remedies and the lack of randomized trials are an obstacle to providing safe use of plant-derived teas.

Development and evaluation of transdermal delivery system of tranylcypromine for the treatment of depression.

Tranylcypromine (logP = 1.34, MW = 133.19g/mol) is a monoamine oxidase inhibitor used in treating major depressive disorder and is available only as oral tablets. Transdermal delivery of tranylcypromine minimizes hepatic and gastrointestinal side effects associated with oral dosing and prevents systemic side effects improving patient compliance. A two-day suspension-based transdermal delivery method was developed in this study, and the delivery of tranylcypromine across dermatomed porcine ear skin was evaluated. Different penetration enhancers were screened, namely, isopropyl myristate, oleyl alcohol, oleic acid, and a combination of oleic acid and oleyl alcohol. Isopropyl myristate was chosen as the penetration enhancer, and suspension-based transdermal patches were formulated with acrylate and polyisobutylene pressure-sensitive adhesives by the solvent evaporation method. The release liner and backing membrane were chosen, and the drying time for each patch was optimized. The optimized patches were characterized for their adhesive properties, drying time, peel test, shear strength, and uniformity in drug content. In vitro permeation studies were performed on dermatomed porcine ear skin using vertical static Franz diffusion cells, and the receptor samples were collected at predetermined time points for 48h. The samples were analyzed in a validated UPLC method. Acrylate-based suspension patch delivered a significantly higher amount of drug (712 ± 21.46μg/cm2) as compared to passive delivery from drug dissolved in propylene glycol (461.49 ± 75.55μg/cm2), reaching the two-day therapeutic target. However, the PIB-based suspension patch delivered 559.25 ± 12.37μg/cm2 of tranylcypromine across the skin but did not reach the required target.

Eye Lesions during HIV/AIDS Infection: About 75 Patients

Ocular attaints during AIDS are multiple and can affect both the ant segment, post, and appendices. Post-segment disorders may be directly related to HIV itself, opportunistic infections, or neoplasia dominated lymphoma. Changes in vision are mainly due to retinitis CMV (most common) and retinitis VZV (most severe) Eye surveillance of AIDS patients is therefore very important. General antiviral treatments do not prevent relapse and have hepatic and renal side effects.

Laparoscopic isolated liver segmentectomy 8 for malignant tumors: techniques and comparison of surgical results with the open approach using a propensity score-matched study.

Anatomic isolated liver segmentectomy 8 (ILSeg8) for malignancies remains technically challenging. The feasibility, safety, and oncologic validity of laparoscopic ILSeg8 are undefined, and thus were evaluated in comparison with the open approach. This study enrolled 35 open and 29 laparoscopic ILSeg8 cases of hepatocellular carcinoma (n = 47), metastatic liver tumors (n = 16), and intrahepatic cholangiocarcinoma (n = 1) at our institution. The surgical techniques were based on the pre-hepatectomy extrahepatic Glissonian pedicle control, followed by cranial-to-caudal parenchymal dissection from the hepatic vein root side. The short- and long-term outcomes after ILSeg8 were retrospectively evaluated and compared between the open and laparoscopic approaches using 1:1 propensity score matching (PSM). Both before and after PSM, the laparoscopic ILSeg8 group had significantly less blood loss, lower postoperative serum bilirubin level, and a shorter postoperative hospital stay than the open group. The overall survival rates were comparable between the laparoscopic and open groups before (P = 0.017) and after (P = 0.043) PSM, with the similar recurrence-free survival rates between the groups. In a multivariable analysis of the cohort before PSM (n = 64), the laparoscopic approach was identified to be an independent factor for favorable overall survival (hazard ratio = 0.20, P = 0.039). Laparoscopic ILSeg8 using the extrahepatic Glissonian approach and hepatic vein root at first parenchymal dissection was feasible, safe, and oncologically acceptable. In ILSeg8 for malignancy, the laparoscopic approach potentially confers short-term advantages over the open approach with comparable long-term outcomes in select patients.

Acipimox Induces the Hepatic Accumulation of Long‐Chain Diacylglycerides and Triglycerides in Severely Burned Sprague Dawley Rats

ObjectivePersistent lipolysis is a hallmark of severe burns, contributing to futile triglyceride cycling and the accumulation of lipid in ectopic tissues. It has been suggested that the administration of acipimox, a potent inhibitor of lipolysis, may blunt the hypermetabolic response to burns. However, what impact massive burns has on the accumulation of individual lipid species in the liver and how this is affected by acipimox treatment is unknown.HypothesisWe hypothesize that large burns results in the accumulation of lipotoxic species within the liver and that this can be prevented by administering acipimox.MethodsThirty‐two male Sprague Dawley rats were randomized to receive either a scald burn (~60% total body surface area) or sham procedure, performed under isoflurane general anesthesia. Afterwards, animals were further randomized to receive either acipimox (50 mg/kg/day) or vehicle (saline) by i.p. injection administered once a day for 7 days. On day 7, animals were euthanized and the liver snap frozen in liquid nitrogen. Liver lipids were extracted by using a chloroform:methanol (2:1) solution and diacylglycerol (DAG), triacylglycerol (TAG), free fatty acids (FFA) and cholesterol esters (CE) separated by thin‐layer chromatography. Afterwards, individual lipid classes were esterified to methyl esters, derivatized using heptane, and analyzed by gas chromatography (GC). The fatty acids C16:0, C18:0, cis/trans C18:1, cis 18:2, C20:0, C22:0, C24:0, and C22:6 were resolved by GC for each of the lipid classes examined.ResultsLiver weights were comparable between groups. Burn injury had no significant effect on the concentration of liver lipids compared to sham treated animals, irrespective of lipid class (P &gt; 0.05). In contrast, the administration of acipimox significantly increased liver C16:0 (2.1‐fold; P &lt; 0.05), trans C18:1 (2.5‐fold; P &lt; 0.05), and cis C18:2 (5.5‐fold; P &lt; 0.05) TAG content in burned animals, when compared to injured animals treated with vehicle. No effect of acipimox on liver lipids was observed in sham treated animals.ConclusionContrary to expectations, acipimox causes the accumulation of long‐chain TAGs in rat liver following massive burns, but this is not observed in response to burn injury alone. The ability of acipimox to cause unwanted hepatic metabolic side effects warrants further investigation before it is used clinically to treat massive burns.

Chemical constituents, anti-hyperuricemic and anti-gouty arthritis activities of extract of Herpetospermum caudigerum

In this paper, we studied the anti-hyperuricemia and anti-gouty arthritis effects of the ethyl acetate extract of Herpetospermum caudigerum (EH), and applied ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) technology to analyze and identify the chemical components of EH. EH can dramatically lower serum uric acid (UA) levels in the hyperuricemia mice model induced by potassium oxazine (PO). In addition, in the gouty arthritis rats model established by sodium urate, the ankle swelling degree, serum uric acid (UA), IL-1β, and TNF-α related inflammatory cytokines all decreased by treating with EH. Consequently, EH appears to have anti-hyperuricemia and anti-gouty arthritis activities, making it a viable option for anti-gout drugs without hepatic and renal side effects, and its effective substances of anti-gout can be further illustrated by UPLC-Q-Orbitrap HRMS analysis of 48 compounds.

Review on Reverse Pharmacology of Jawarhar Mahakashaya Drugs for Anti-pyretic Activity in Momoherbal and Polyherbal Form

Ayurvedic Jawarahara Mahakashaya (JhMh) includes Sariva, Sharkara, Patha, Manjishtha, Draksha, Pilu, Parushaka, Abhaya, Amalaka and Bibhitaka drugs as a set of ten herbal drugs, means this set of drug is effective in countering Jawar (fever) in single drug form or combined formulation. Globally the most accepted drugs which are used to cure pyrexia are NSAIDS. It is reported that most of these chemical antipyretic formulations has been associated with gastrointestinal, renal, hepatic, CNS and dermatological side effects. Extensive literature searches both electronic online databases on concerning issues. Drugs of Jawarhar Mahakashaya in monoherbal and polyherbal form have shown significant antipyretic activity in pre-clinical set up as mentioned in Ayurvedic literatures. The main aim of this paper is to review reverse pharmacology of JhMh drugs is described in terms of Ayurveda and is supported parallelly with the facts and findings of scientific researches done in modern science. JhMh can replace the side effects of chemical drugs and stand as sustainable antipyretics if used judicious.

Probiotics counteract hepatic steatosis caused by ketogenic diet and upregulate AMPK signaling in a model of infantile epilepsy.

SummaryBackgroundInfantile spasms syndrome (IS) is a type of epilepsy affecting 1.6 to 4.5 per 10,000 children in the first year of life, often with severe lifelong neurodevelopmental consequences. Only two first-line pharmacological treatments currently exist for IS and many children are refractory to these therapies. In such cases, children are treated with the ketogenic diet (KD). While effective in reducing seizures, the diet can result in dyslipidemia over time.MethodsEmploying a neonatal Sprague-Dawley rat model of IS, we investigated how the KD affects hepatic steatosis and its modulation by a defined probiotic blend. A combination of multiple readouts, including malondialdehyde, fatty acid profiles, lipid metabolism-related enzyme mRNA expression, mitochondrial function, histone deacetylase activity, cytokines and chemokines were evaluated using liver homogenates.FindingsThe KD reduced seizures, but resulted in severe hepatic steatosis, characterized by a white liver, triglyceride accumulation, elevated malondialdehyde, polyunsaturated fatty acids and lower acyl-carnitines compared to animals fed a control diet. The KD-induced metabolic phenotype was prevented by the co-administration of a blend of Streptococcus thermophilus HA-110 and Lactococcus lactis subsp. lactis HA-136. This probiotic blend protected the liver by elevating pAMPK-mediated signaling and promoting lipid oxidation. The strains further upregulated the expression of caspase 1 and interleukin 18, which may contribute to their hepatoprotective effect in this model.InterpretationOur results suggest that early intervention with probiotics could be considered as an approach to reduce the risk of hepatic side effects of the KD in children who are on the diet for medically indicated reasons.FundingThis study was funded by the Alberta Children's Hospital Research Institute and Mitacs Accelerate Program (IT16942).