Laparoscopic Caudate Resection: How to Safely Manage the Spiegel/IVC Interface.

BACKGROUND: Minimally invasive caudate lobectomy, or even paracaval caudate resection, can be associated with significant bleeding due to its abutment of inferior vena cava (IVC), portal pedicle and hepatic veins.1-3 This risk can be magnified by cirrhosis as well as response to neoadjuvant therapy (a common phenomenon after excellent response to neoadjuvant chemotherapy), leading to obliteration or even fusion of the hepato-caval space.4-7 PATIENT: A 68-year-old female with stage IVa colorectal adenocarcinoma was found to have a single liver metastasis (3.8 × 3.1 cm) in the paracaval caudate lobe. The patient received four cycles of neoadjuvant chemotherapy, leading to inflammatory fusion of the hepato-caval space. Despite this, the patient underwent a safe laparoscopic Spiegel process resection. TECHNIQUE: Prior to surgery, three-dimensional liver and port site modeling was performed to optimize the understanding of the spatial relationship between the tumor, IVC, and portal-hepatic veins. Following inflow control of portal veinous branches, the fused hepato-caval space was dissected. The adhesions were then sharply dissected to mobilize the paracaval caudate lobe off the IVC. Using scissors rather than an energy device reduced the risk of inadvertent thermal injury to the IVC. CONCLUSION: Preoperative virtual hepatectomy facilitates surgical planning, increasing the understanding of the tumor/vessel relationship and port placement. In case of a fused hepato-caval space, low central venous pressure and judicious management of short hepatic vein branches are the key for a successful dissection. Moreover, anticipation of a fused hepato-caval space and its strategic management are paramount when performing a minimally invasive caudate resection.

Single-Cell RNA Sequencing of Sox17-Expressing Lineages Reveals Distinct Gene Regulatory Networks and Dynamic Developmental Trajectories.

During early embryogenesis, the transcription factor SOX17 contributes to hepato-pancreato-biliary system formation and vascular-hematopoietic emergence. To better understand Sox17 function in the developing endoderm and endothelium, we developed a dual-color temporal lineage-tracing strategy in mice combined with single-cell RNA sequencing to analyze 6934 cells from Sox17-expressing lineages at embryonic days 9.0-9.5. Our analyses showed 19 distinct cellular clusters combined from all 3 germ layers. Differential gene expression, trajectory and RNA-velocity analyses of endothelial cells revealed a heterogenous population of uncommitted and specialized endothelial subtypes, including 2 hemogenic populations that arise from different origins. Similarly, analyses of posterior foregut endoderm revealed subsets of hepatic, pancreatic, and biliary progenitors with overlapping developmental potency. Calculated gene-regulatory networks predict gene regulons that are dominated by cell type-specific transcription factors unique to each lineage. Vastly different Sox17 regulons found in endoderm versus endothelial cells support the differential interactions of SOX17 with other regulatory factors thereby enabling lineage-specific regulatory actions.

Modified Ex Vivo Renal Reconstruction to Facilitate Fenestrated-Branched Endovascular Repair of a Thoracoabdominal Aortic Aneurysm.

PURPOSE: To report the use of modified ex vivo renal artery (RA) reconstruction in a patient with 2 small right RAs (RRAs) in anticipation of planned fenestrated-branched endovascular aortic repair (FB-EVAR) of thoracoabdominal aortic aneurysm (TAAA). CASE REPORT: A staged hybrid repair was utilized in a patient with Extent II TAAA involving celiac axis (CA), superior mesenteric artery (SMA), single left RA (LRA), and 2 small (<3 mm) RRAs. The first-stage operation consisted of hepato-renal bypass using modified ex vivo renal reconstruction with single end-to-end anastomosis to both RAs using a saphenous vein graft. A second stage FB-EVAR was performed using patient-specific manufactured stent-graft with 3 fenestrations for the CA, SMA, and LRA 6 weeks later. The patient recovered with no complications. At 4 years, the patient had widely patent hepato-renal bypass and target vessels with normal renal function. CONCLUSION: The use of adjunctive hybrid procedures may optimize or facilitate FB-EVAR. In this patient, salvage of 2 small RAs was not ideally suited for branch stenting but was possible using modified ex vivo RA reconstruction with preservation of kidney parenchyma and function. CLINICAL IMPACT: This case report illustrates a hybrid approach to overcome one of the most frequent limitations to total endovascular incorporation of renal arteries, eg small diameter, early bifurcation and multiple vessels. The modified ex vivo technique allows meticulous renal artery reconstruction without the deleterious effect of warm ischemia and without the cumbersome reconstruction of ureter and vein that is needed with traditional on table ex vivo auto transplantation. The technique is used in a minority of cases and adds the morbidity of open approach. Case selection is of paramount importance.

Recurrence-risk stratification using the Beppu score and selection of perioperative chemotherapy for colorectal liver metastases.

The annual postoperative disease-free survival for colorectal liver metastases can be easily estimated by weighting six preoperative clinical parameters (Beppu score). We identified three recurrence-risk stratification groups: the low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). For low-, moderate-, and high-risk patients, hepatectomy alone, hepatectomy with adjuvant chemotherapy, and hepatectomy with preoperative chemotherapy are recommended, respectively. The Beppu score enables the decision on the necessity and timing of perioperative chemotherapy.

Hepatic Oxygenation Changes and Symptomatic Intradialytic Hypotension.

INTRODUCTION: Clinical studies on differences among changes in cerebral and hepatic oxygenation during hemodialysis (HD) in patients with and without intradialytic hypotension (IDH) are limited. We investigated changes in intradialytic cerebral and hepatic oxygenation before systolic blood pressure (SBP) reached the nadir during HD and compared these differences between patients with and without symptomatic IDH. METHODS: We analyzed data from 109 patients with (n = 23) and without (n = 86) symptomatic IDH who were treated with HD. Cerebral and hepatic regional oxygen saturation (rSO2), as a marker of tissue oxygenation and circulation, was monitored during HD using an INVOS 5100c oxygen saturation monitor. Changes in cerebral or hepatic rSO2 when SBP reached the nadir during HD were compared between the groups of patients. RESULTS: The cerebral rSO2 before HD in patients with and without symptomatic IDH was 49.7 ± 11.2% and 51.3 ± 9.1% (p = 0.491). %Changes in cerebral rSO2 did not significantly differ between the two groups from 60 min before the SBP nadir during HD. Hepatic rSO2 before HD in patients with and without symptomatic IDH was 58.5 ± 15.4% and 57.8 ± 15.9% (p = 0.869). The %changes in hepatic rSO2 were significantly lower in patients with symptomatic IDH than in those without throughout the observational period (p < 0.001). We calculated the area under the receiver operating characteristic curve (AUC) and estimated cutoff values for changes in hepatic rSO2 as a symptomatic IDH predictor. The predictive ability at 5 and 40 min before symptomatic IDH onset was excellent, with AUCs and cutoff values of 0.847 and 0.841, and -10.9% and -5.0%, respectively. CONCLUSIONS: Hepatic oxygenation significantly decreased more in patients with symptomatic IDH before its onset, than in those without symptomatic IDH, whereas changes in cerebral oxygenation did not differ. Evaluating changes in hepatic oxygenation during HD might help to predict symptomatic IDH.

Assessment of Silver Nanoparticles Derived from Brown Algae Sargassum vulgare: Insight into Antioxidants, Anticancer, Antibacterial and Hepatoprotective Effect.

Algae are used as safe materials to fabricate novel nanoparticles to treat some diseases. Marine brown alga Sargassum vulgare are used to fabricate silver nanoparticles (Sv/Ag-NPs). The characterization of Sv/Ag-NPs was determined by TEM, EDX, Zeta potential, XRD, and UV spectroscopy. The Sv/Ag-NPs were investigated as antioxidant, anticancer, and antibacterial activities against Gram-positive bacteria Bacillus mojavensis PP400982, Staphylococcus caprae PP401704, Staphylococcus capitis PP402689, and Staphylococcus epidermidis PP403851. The activity of the Sv/Ag-NPs was evaluated as hepatoprotective in vitro in comparison with silymarin. The UV-visible spectrum of Sv/Ag-NPs appeared at 442 nm; the size of Sv/Ag-NPs is in range between 6.90 to 16.97 nm, and spherical in shape. Different concentrations of Sv/Ag-NPs possessed antioxidant, anticancer activities against (HepG-2), colon carcinoma (HCT-116), cervical carcinoma (HeLa), and prostate carcinoma (PC-3) with IC50 50.46, 45.84, 78.42, and 100.39 µg/mL, respectively. The Sv/Ag-NPs induced the cell viability of Hep G2 cells and hepatocytes treated with carbon tetrachloride. The Sv/Ag-NPs exhibited antibacterial activities against Staphylococcus caprae PP401704, Staphylococcus capitis PP402689, and Staphylococcus epidermidis PP403851. This study strongly suggests the silver nanoparticles derived from Sargassum vulgare showed potential hepato-protective effect against carbon tetrachloride-induced liver cells, and could be used as anticancer and antibacterial activities.

Bile acids promote lipopolysaccharide clearance via the hepato-biliary pathway in broiler chickens.

Lipopolysaccharide (LPS) acts as a trigger that disrupts metabolic functions and the immune system. While bile acids (BA) have detoxification and anti-inflammatory effects, their role in promoting LPS excretion in broiler chickens remains unclear. This study aimed to investigate the potential of exogenous BA to enhance hepatic clearance of LPS and thereby potentially alleviate LPS-induced liver injury in broiler chickens. Forty-five 21-day-old male broiler chickens were randomly assigned to three groups: the control group, which received daily intraperitoneal injections of a solvent for LPS treatment and a gavage solvent for BA treatment; the LPS group, which received daily intraperitoneal injections of 0.5 mg/kg body weight LPS and a gavage solvent for BA treatment; the LPS + BA group, which received daily intraperitoneal injections of 0.5 mg/kg body weight LPS and 60 mg/kg body weight BA by gavage. BA administered by gavage protected the broiler chickens from increases in liver and spleen indices, systemic inflammatory response, and hepatic damage induced by LPS. Hepatic clearance of LPS was enhanced, as evidenced by decreased serum LPS levels and accelerated excretion into the gallbladder. Additionally, the LPS-induced downregulation of detoxification genes, including those for the lipoprotein receptor and bile acids export pump, was reversed by BA administered by gavage. Furthermore, nuclear transcription factors such as the Farnesoid X receptor (FXR) and Liver X receptor α (LXRα) were enhanced in BA-treated broiler chickens. These findings suggest that BA administration via gavage enhances hepatic LPS clearance through the upregulation of hepatic uptake and efflux proteins, likely mediated by the activation of nuclear transcription factors FXR and LXRα.

Efficacy of Unilateral External Oblique Intercostal Fascial Plane Block Versus Subcostal TAP Block in Laparoscopic Cholecystectomy: Randomized, Prospective Study.

BACKGROUND: This study aimed to evaluate the effectiveness of unilateral external oblique intercostal nerve block (EOIB) in laparoscopic cholecystectomy surgery. MATERIAL AND METHODS: After ethics committee approval, ASA I-II patients aged 18-70 who would undergo laparoscopic cholecystectomy surgery were included in the study. The patients were divided into two groups, external oblique intercostal nerve block (Group EOIB) and oblique subcostal transversus abdominis plane block (Group OSTAP). After surgery, EOIB or OSTAP block was administered with 20 mL of .25% bupivacaine then routine analgesia protocol was applied with iv paracetamol, and tramadol. Visual analog scale (VAS) scores and patient-controlled analgesia (PCA) consumption were monitored 24 hours after the operation. It was administered 25 mg pethidine as a rescue analgesic to patients with VAS ≥4. RESULTS: Thirty six patients for Group EOIB and thirty four patients for Group OSTAP were included in the study. Lower VAS scores were observed in all groups. When PCA consumption, side effects, rescue analgesia consumption, and patient satisfaction were evaluated, there was no statistically significant difference between the groups (P > .05). CONCLUSION: It was observed that EOIB showed similar analgesic activity to the OSTAP block. EOIB may also be a part of postoperative multimodal analgesia by reducing postoperative opioid consumption in LC.

Levilactobacillus brevis MZ384011 and Levilactobacillus brevis MW362779 can mitigate lead induced hepato-renal damage by regulating visceral dispersion and fecal excretion.

Heavy metal pollution is a global issue. Current study provides evidence on Pb toxicity ameliorative potential and safe nature of Levilactobacillus brevis MZ384011 (S1) and Levilactobacillus brevis MW362779 (S2), isolated from carnivore gut and human milk, respectively. In a 60-days experiment, the rats were distributed into six groups. G-I, G-V and G-VI were kept on normal diet, while GII-IV were fed on lead nitrate (500 mg/kg) supplemented food, throughout experiment. After confirmation of Pb toxicity in GII-IV at 15th day, S1 was orally administered to G-III and G-V while S2 was given to G-IV and G-VI at a dose of 1 × 109 CFU/animal/day. On day 60 of experiment, positive control (G-II) displayed significant reduction in body weight, total protein, albumin, globulin, mineral profile, erythrocyte count, hemoglobin, hematocrit and hematological indices and elevation in leukocyte count, alanine aminotransferase, aspartate aminotransferase, bilirubin, uric acid and creatinine along with alterations in hepato-renal architecture. With reference to G-II, the G-III and G-IV displayed significant improvement in all aforementioned parameters, 40-60% reduction in tissue Pb levels (blood, liver, kidney and adipose tissue) and elevation in fecal Pb contents (p = 0.000). The groups V and VI did not show any sign of toxicity. The findings confirm that strains are safe for biological application and can reverse Pb toxicity by facilitating fecal Pb excretion and reducing its systemic dispersal. To best of our information this is the first report on Pb toxicity ameliorative role of Levilactobacillus brevis from human milk, the safest source.

The hepato-ovarian axis: genetic evidence for a causal association between non-alcoholic fatty liver disease and polycystic ovary syndrome.

BACKGROUND: Recent studies found associations between non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), but the causal nature of this association is still uncertain. METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) analysis to test for the causal association between NAFLD and PCOS using data from a large-scale biopsy-confirmed NAFLD genome-wide association study (GWAS) (1483 cases and 17,781 controls) and PCOS GWAS (10,074 cases and 103,164 controls) in European ancestries. Data from glycemic-related traits GWAS (in up to 200,622 individuals) and sex hormones GWAS (in 189,473 women) in the UK Biobank (UKB) were used in the MR mediation analysis to assess potential mediating roles of these molecules in the causal pathway between NAFLD and PCOS. Replication analysis was conducted using two independent datasets from NAFLD and PCOS GWASs in the UKB and a meta-analysis of data from FinnGen and the Estonian Biobank, respectively. A linkage disequilibrium score regression was conducted to assess genetic correlations between NAFLD, PCOS, glycemic-related traits, and sex hormones using full summary statistics. RESULTS: Individuals with higher genetic liability to NAFLD were more likely to develop PCOS (OR per one-unit log odds increase in NAFLD: 1.10, 95% CI: 1.02-1.18; P = 0.013). Indirect causal effects of NAFLD on PCOS via fasting insulin only (OR: 1.02, 95% CI: 1.01-1.03; P = 0.004) and further a suggestive indirect causal effect via fasting insulin in concert with androgen levels were revealed in MR mediation analyses. However, the conditional F statistics of NAFLD and fasting insulin were less than 10, suggesting likely weak instrument bias in the MVMR and MR mediation analyses. CONCLUSIONS: Our study suggests that genetically predicted NAFLD was associated with a higher risk of developing PCOS but less evidence for vice versa. Fasting insulin and sex hormones might mediate the link between NAFLD and PCOS.

Association between sarcopenia and postoperative complications in patients undergoing surgery for gastrointestinal or hepato-pancreatico-biliary cancer.

BACKGROUND AND OBJECTIVES: Despite surgical advances, postoperative complications persist, affecting oncologic outcomes and increasing treatment costs. It is important to identify a marker that can predict postoperative complications, which can help prehabilitate patients before surgery. This study evaluated sarcopenia as a predictive marker of postoperative complications in patients undergoing surgery for gastrointestinal (GI) or hepato-pancreatico-biliary (HPB) cancer. METHODS: Sarcopenia was assessed using the skeletal muscle index at the third lumbar vertebra on abdominal computed tomography. The predictive ability of sarcopenia was evaluated by adjusting for other clinicopathological factors. RESULTS: Of the 210 patients, 81 (38.57%) were sarcopenic. The overall morbidity and mortality were 33.81% and 2.86%, respectively. Major complications (Clavien-Dindo Grade ≥ III) were observed in 10.95% patients and sarcopenic patients were significantly more likely to develop major complications (p = 1.42 × 10-10 ). Sarcopenia (p = 6.13 × 10-6 ; odds ratio = 12.29) independently predicted postoperative complications and prolonged hospital stay (p = 0.01). CONCLUSION: Sarcopenia objectively predicted the development of postoperative complications and prolonged hospital stay in patients undergoing surgery for GI or HPB cancer. This may facilitate the prehabilitation of patients planned for surgery to reduce the risk of complications.

Justicia carnea extracts ameliorated hepatocellular damage in streptozotocin-induced type 1 diabetic male rats via decrease in oxidative stress, inflammation and increasing other risk markers.

IntroductionDiabetes mellitus is still a raging disease not fully subdued globally, especially in Africa. Our study aims to evaluate the anti-diabetic potentials of Justicia carnea extracts [crude (JCC), free (JFP) and bound phenol (JBP) fractions], in streptozotocin (STZ)-induced type-1 diabetes in male albino rats.Materials and MethodsAbout thirty (30) animals were induced for type 1 diabetes with STZ; thereafter, treatment began for 14 days, after which the animals were euthanized, blood/serum was collected, the liver was removed and divided into two portions, for biochemical and histopathological analyses. Standard procedures were used to evaluate the liver biomarkers, like alanine transaminase (ALT), fructose-1,6-bisphosphatase, glucose-6- phosphatase, hexokinase activities, albumin, bilirubin, hepatic glucose concentrations; antioxidant status and pro- and anti-inflammatory cytokines were similarly assessed.ResultsThese results revealed that the extracts ameliorated the harmful effects of STZ-induced diabetes in the liver by enhancing the activities of liver-based biomarkers, reducing the concentrations of pro-inflammatory cytokines and increasing the anti-inflammatory cytokine.DiscussionThe results agreed with previous research, and the free phenol fraction showed excellent results compared to othersConclusionThese suggested that J. carnea could serve as an alternative remedy in ameliorating liver complications linked to oxidative damage and inflammation in STZ-induced type-1 diabetes.

Utility and diagnostic accuracy of intraoperative frozen sections in hepato-pancreato-biliary surgical pathology.

BACKGROUND AND PURPOSE: Hepato-pancreato-biliary (HPB) surgeries are one of the most challenging and complex procedures. Intraoperative frozen section (IFS) diagnosis plays a pivotal role in management decisions. Comprehensive large cohort studies evaluating utility of IFS in HPB malignancies are lacking. This study aimed to evaluate the accuracy of frozen section analysis and to analyse discrepancies and impact of IFS on the surgical decisions. PATIENTS AND METHODS: This was a retrospective study of IFS received for the HPB specimens between years 2009 and 2021. The results were compared to the permanent sections to evaluate diagnostic accuracy, sensitivity and specificity. Indications, disagreements and impact on the surgical management were analysed. RESULTS: A total of 1008 specimens were evaluated: bile duct margin (279; 27.7%), gallbladder (203; 20.1%), liver lesions (125 cases; 12.4%), lymph nodes (147; 14.6%), pancreatic margin (120; 11.9%) and deposits (134; 13.3%). IFS were diagnosed as negative for malignancy (805; 79.9%), positive for dysplasia (8; 0.8%), suspicious for malignancy (6; 0.6%) and positive for malignancy (189; 18.8%). The overall diagnostic accuracy was 98.4%, and the discordant rate was 1.6%. The sensitivity, specificity, positive predictive value and negative predictive value were 94.7%, 99.4%, 97.5% and 98.6% respectively. The most important reason of discordant results was technical, followed by interpretational and sampling errors. CONCLUSION: The study demonstrates high diagnostic accuracy (98.4%) of IFS in a large dataset of HPB specimens. This comprehensive analysis apprises of the indications, errors and the impact of IFS diagnosis on subsequent HPB surgical management.

An umbrella review of the surgical performance of Harmonic ultrasonic devices and impact on patient outcomes.

BACKGROUND: For thirty years, the Harmonic scalpel has been used for precise dissection, sealing and transection. There are numerous meta-analyses on individual surgical procedures with Harmonic, but no overarching review covering all the areas. This umbrella review seeks to summarize the clinical results from the use of Harmonic across surgical fields and broadly quantify its effects on patient outcomes. METHODS: MEDLINE, EMBASE, and Cochrane Databases were searched for meta-analyses (MAs) of randomized controlled trials (RCTs) comparing Harmonic devices to conventional techniques or advanced bipolar (ABP) devices. For each procedure type, the most comprehensive MAs were evaluated. RCTs not already analysed in a MA were also included. Operating time, length of stay, intraoperative blood loss, drainage volume, pain, and overall complications were evaluated, and the methodological quality and certainty of evidence were assessed. RESULTS: Twenty-four systematic literature reviews were identified on colectomy, hemorrhoidectomy, gastrectomy, mastectomy, flap harvesting, cholecystectomy, thyroidectomy, tonsillectomy, and neck dissection. There were also 83 RCTs included. In every MA evaluated, Harmonic devices were associated with either statistically significant or numerical improvements in every outcome compared with conventional techniques; most MAs reported a reduction in operating time of ≥ 25 min. Harmonic versus ABP device MAs in colectomy and thyroidectomy showed no significant differences in outcomes. CONCLUSION: Across surgical procedures, Harmonic devices demonstrated improved patient outcomes for operating time, length of stay, intraoperative bleeding, drainage volume, pain, and overall complications compared to conventional techniques. Additional studies are required to assess differences between Harmonic and ABP devices.

Is the use of a routine intraoperative cholangiogram necessary in laparoscopic cholecystectomy?

INTRODUCTION: Although laparoscopic cholecystectomy (LC) has been standard of care for symptomatic gallstone disease for almost 30 years, the use of routine intraoperative cholangiogram (IOC) remains controversial. There are marked variations in the use IOC during LC internationally. Debate has continued about its benefit, in part because of inconsistent benefit, time, and resources required to complete IOC. This literature review is presented as a debate to outline the arguments in favour of and against routine IOC in laparoscopic cholecystectomy. METHODS: A standard literature review of PubMed, Medline, OVID, EMBASE, CINHIL and Web of Science was performed, specifically for literature pertaining to the use of IOC or alternative intra-operative methods for imaging the biliary tree in LC. Two authors assembled the evidence in favour, and two authors assembled the evidence against. RESULTS: From this controversies piece we found that there is little discernible change in the number of BDIs requiring repair procedures. Although IOC is associated with a small absolute reduction in bile duct injury, there are other confounding factors, including a change in laparoscopic learning curves. Alternative technologies such as intra-operative ultrasound, indocyanine green imaging, and increased access to ERCP may contribute to a reduction in the need for routine IOC. CONCLUSIONS: In spite of 30 years of accumulating evidence, routine IOC remains controversial. As technology advances, it is likely that alternative methods of imaging and accessing the bile duct will supplant routine IOC.

USE of Biodegradable STENTS in Pancreaticoduodenectomy: Initial Experience.

Background. Plastic stents have been used to avoid postoperative pancreatic fistula (POPF) following Whipple's Pancreaticoduodenectomy (WPD), but they may cause some stent-related complications. Biodegradable stents have been recently introduced and might be a safe alternative. Here we present our initial experience with their use. Methods. Between March 1, 2020, and September 30, 2020, ten (10) consecutive patients underwent WPD. They all had conventional two-layer pancreaticojejunostomy with the placement of an internal biodegradable stent. They were assessed for technical feasibility, pancreatic leak, and stent-related complications. Results. The use of biodegradable stents was technically feasible in all patients, despite some difficulties in insertion due to stent stiffness and design. After a median follow-up period of 124 days, none of the patients suffered POPF. One patient had a biochemical pancreatic leak with no clinical significance. The median hospital stay was 7 days, and there were no stent-related complications. Conclusion. Biodegradable stents are technically feasible and safe in WPD with good short-term outcomes. They might provide a better alternative to plastic stents and their potential complications. Larger long-term studies are needed to validate efficacy and safety. Few modifications of the stent's design might be needed to facilitate use in open surgery.

Dietary supplementations modulate the physiological parameters, fatty acids profile and the growth of red claw crayfish (Cherax quadricarinatus).

An optimal diet is an important factor for the proper growth and health of crustaceans. However, the regulation of antioxidant activity and non-specific immunity related to the consumption of feed additives has not been studied in RC-crayfish. Triplicate groups of 20 crayfish/tank (36.72 ± 0.70 g) fed with a basal diet and sixteen experimental diets that contained five feed additives with four grade levels (40, 160, 240 and 320 mg/kg vitamin E, 2, 4, 6 and 8 g/kg nucleotides, 2, 4, 6 and 8 g/kg Haematococcus pluvialis, 5, 10, 15 and 20 g/kg arachidonic acid and 2.5, 5, 10 and 15 g/kg yeast extract) on physiological parameters, fatty acids profile and growth of Cherax quadricarinatus for a period of 70 days by using orthogonal array method (L16 45 ). The results showed that the antioxidants activity in the haemolymph and hepatopancreas were both higher in crayfish fed with diets NO. 9 to 12 than others. Also, all the diets except diets NO. 13 to 16 showed lower free radicals contents than the control group. Similarly, significantly higher non-specific immune parameters were observed in the hepatopancreas of crayfish supplementations than those fed a control diet. Biochemical parameters related to protein profile in haemolymph increased in diets NO. 9 to 12 and then decreased in control and diets NO. 13 to 16, while the highest biochemical parameters related to lipid profile except HDL-c contents in haemolymph were observed in crayfish fed the control diet. Fatty acid composition in the hepatopancreas, muscle and ovary of RC-crayfish was significantly influenced by using the combination of Vit E, NT, H. pluvialis and YP compared to the control group. Compared to all treatments, RC-crayfish fed with diets NO. 2 and 12 had significantly stimulated higher growth performance and feed utilisation. Overall, our results suggest that diets supplemented with Vit E level of 240 mg/kg, in combination with 8 g/kg NT, 4 g/kg, H. pluvialis, 5 g/kg ARA and 10 g/kg YP are the promising treatments to increase antioxidants activity, non-specific immune response, fatty acids composition and growth of RC-crayfish. However, high dietary supplementations level can reduce antioxidants activity, immunity and inhibit growth.

Acute Porphyria: An Unusual Case Of Quadriparesis, Hypertension, Recurrent Severe Cyclic Abdominal Pain, And Seizures.

Porphyria refers to a rare group of genetically inherited or acquired disorders that arise due to reduced metabolic activity of any of the enzymes in the haem biosynthetic pathway. Defect in any enzyme causes the presentation of symptoms of porphyria. The epidemiology of Acute Intermittent Porphyria (AIP) is complicated because of its rarity and delay in diagnosis. We present the case of a seven-year-old girl who presented with multisystem involvement; her symptoms were quadriparesis, hypertension, recurrent severe cyclic abdominal pain, and seizures. These symptoms together were not explained by the differentials taken into account. She presented before puberty with no family history of such conditions, while being born of consanguineous marriage. Her symptoms along with urinary porphobilinogen positivity test helped to reach the diagnosis of AIP in the absence of cutaneous manifestations. This case highlights the variable presentation of porphyria and emphasises the importance of appropriate and timely diagnosis and management in these patients.

The Protective Potential of Petroselinum crispum (Mill.) Fuss. on Paracetamol-Induced Hepatio-Renal Toxicity and Antiproteinuric Effect: A Biochemical, Hematological, and Histopathological Study.

Background and Objectives: Paracetamol overdose is a significant global issue due to its widespread use, which can lead to a lack of awareness regarding its potential side effects. Paracetamol can harm the liver, possibly resulting in liver failure. Conversely, this study employed extracts from Petroselinum crispum (PC), known for its rich content of bioactive compounds, with demonstrated antioxidant properties shown in previous research as well as protective effects against various diseases. The primary objective of this study was to investigate the potential protective effects of Petroselinum crispum on altered hematological and biochemical parameters in the blood of rats exposed to paracetamol. Materials and Methods: The study involved twenty Wistar rats divided into four groups. Different groups of male rats were administered PC extract at 200 mg/kg body weight daily for 15 days, along with a standard reference dose of paracetamol at 200 mg/kg. The study assessed hepatoprotection capacity by analyzing liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, albumin, and lipid profiles. Renal safety was evaluated through creatinine, urea, uric acid, lactate dehydrogenase (LDH), and total protein. Additionally, histopathological examinations of the liver and kidneys were conducted. Results: Following Paracetamol overdose, there were reductions in hemoglobin levels, serum total protein, albumin, and uric acid. Paracetamol overdose also elevated levels of several blood biomarkers, including creatinine, urea, nitrogen, ALT, AST, triglycerides, LDH activity, white blood cell count, and platelet count compared to the control group. However, using an ethanolic extract of Petroselinum crispum significantly mitigated the severity of these alterations and the extent of the effect correlated with the dose administered. Parsley extract helped prevent proteinuria and low hemoglobin, which are common side effects of Paracetamol. Conclusions: Therefore, parsley may hold promise in managing liver and kidney conditions-particularly in addressing proteinuria. Ultimately, these results may have implications for human health by potentially mitigating paracetamol-induced renal, hepatic, and hematological toxicity.

Apigenin alleviates cancer drug Sorafenib induced multiple toxic effects in Swiss albino mice via anti-oxidative stress.

Sorafenib is an FDA-approved chemotherapeutic drug used as standard therapy for advanced-stage cancers. However, Sorafenib-induced multiple adverse effects are a major limitation that directly impacts patients' physical and physiological well-being. Therefore, it is vital to identify agents that can lessen the associated adverse effects and enhance efficacy. Apigenin, a dietary plant flavone, is a bioactive-compound present in fruits and vegetables having anti-oxidant, anti-inflammatory, and anti-cancer properties. Our study aimed to investigate Sorafenib-induced toxic effects at genomic, cellular, and tissue level and the potential protective effects of Apigenin. To achieve our goal, we treated Swiss albino mice with Apigenin (50 mg/kg bw) alone or in combination with Sorafenib (40 mg/kg bw). Next, we performed DNA interaction, genotoxicity, oxidative damages, anti-oxidant activities, liver enzyme levels, and histopathological studies. We demonstrated that Apigenin and Sorafenib bind DNA via electrostatic interaction. Further, Sorafenib induces genetic, oxidative, and tissue damages characterized by an increase in chromosomal aberrations and micronucleus, reactive oxygen species (ROS) and reactive nitrogen species (RNS), oxidative and DNA damage, lipid peroxidation, and hepato-renal damages, and a decrease in antioxidant-enzymes. Interestingly, the Sorafenib-induced adverse effects were ameliorated by Apigenin. Our findings indicate that Apigenin has protective effects against Sorafenib-induced toxicity and could be combined with Sorafenib to lessen its adverse effects and enhance its efficacy. However, further pre-clinical and clinical studies are required to evaluate Apigenin's effectiveness with Sorafenib.