Altered Liver Function Research Articles

Abstract 4136614: The design of novel therapeutics that target the L-type calcium channel to prevent hypertrophic cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is an inherited autosomal dominant disease of the sarcomere. Pathogenic features include ventricular hypertrophy, increased myofilament calcium sensitivity, myocardial fibrosis, and diastolic dysfunction. At the level of the myocyte there is cytoskeletal disarray, hypercontractility and altered mitochondrial function. Mitochondrial dysfunction is considered to be a key driver in HCM pathology. Research question: We previously demonstrated that the L-type Ca 2+ channel plays a role in the development of HCM facilitated by a structural-functional communication with mitochondria that can be regulated via the alpha interaction domain (AID) of the channel. In search of a preventative HCM therapy, we explored the efficacy of amino acid peptide variants that correspond to the AID of the cardiac L-type Ca 2+ channel. Methods and Results: Consistent with in silico predictions , competition binding assays confirmed that 4 variant peptides bound with higher affinity to the beta subunit than the AID peptide. In vitro studies confirmed that 3 of the 4 peptides could decrease the characteristic hypermetabolic state in myocytes isolated from a murine model of human HCM ( cTnI-G203S ). In vivo treatment of cTnI-G203S mice with peptide variants prevented the development of HCM and the development of fibrosis, in the absence of alterations in blood pressure, or kidney and liver function or changes in behaviour. Of note, the peptide variants also significantly improved contractile function. Similar effects were measured in αMHC 403/+ mice expressing the MYH6 mutation. Conclusions: Here we describe a first in class therapy that uniquely targets the L-type Ca 2+ channel to modify mitochondrial function and prevent hypertrophic cardiomyopathy. The peptides may be effective for treatment of HCM broadly because the mechanism of action involves the modification of mitochondrial function and impaired energy metabolism that is a common characteristic and driver of the pathology.

Redefining space pharmacology: bridging knowledge gaps in drug efficacy and safety for deep space missions

The space environment is incredibly hostile, and humans are vulnerable in such conditions. Astronauts encounter various stress factors during a space journey, including radiation, microgravity, forceful acceleration during launch, altered magnetic fields, and confinement. These stressors significantly impact the human body homeostasis, leading to physio-pathological adaptations, loss of bone density, muscle atrophy, cardiovascular deconditioning, alterations in liver function, vestibular adaptations, and immune system dysregulation. These alterations can potentially influence drug pharmacokinetics and pharmacodynamics, affecting the efficacy and safety of medications administered to astronauts. Due to the limited number of studies on pharmaceuticals conducted in microgravity conditions, it’s challenging to assess the effectiveness and stability of these medications during spaceflight. The objective of the present work is to compare the state-of-the-art knowledge on PK/PD changes and factors likely to affect them during spaceflight, with the subjective perception of the problem by a collection of separate interviews conducted with seven experts in the field. The interviewees were chosen as “experts,” i.e., representatives in a specific discipline, who possess knowledge and experience in space pharmacology, physiology, or biology. Thus, our panel included astronauts, space surgeons, and scientists aiming to bridge the lack of experimental data in the literature. Each interview explores assorted aspects of space physiology and pharmacology, including drug use and storage onboard the ISS; notable consideration has arisen regarding the current research gaps and future space expeditions. All the interviews were held remotely using online conferencing software. None of the interviewees could provide a comprehensive overview regarding potential changes in drugs PK/PD in microgravity conditions. Further, any medication brought on board (whether as part of an astronaut’s medical kit or stored in the ISS pharmacy) is destroyed, thereby suppressing the possibility of analyzing any degradation products resulting from long-term exposure to microgravity and radiation. According to these results, the use of drugs without understanding how they are genuinely absorbed, distributed, metabolized, and excreted in microgravity conditions is concerning, posing risks for drug effectiveness. Conducting genotyping and phenotyping on astronauts would be beneficial for developing personalized pharmacological countermeasures for each astronaut and anticipating expected drug metabolism changes during space missions.

Apoptosis, Mitochondrial Autophagy, Fission, and Fusion Maintain Mitochondrial Homeostasis in Mouse Liver Under Tail Suspension Conditions

Microgravity can induce alterations in liver morphology, structure, and function, with mitochondria playing an important role in these changes. Tail suspension (TS) is a well-established model for simulating the effects of microgravity on muscles and bones, but its impact on liver function remains unclear. In the current study, we explored the regulatory mechanisms of apoptosis, autophagy, fission, and fusion in maintaining liver mitochondrial homeostasis in mice subjected to TS for 2 or 4 weeks (TS2 and TS4). The results showed the following: (1) No significant differences were observed in nuclear ultrastructure or DNA fragmentation between the control and TS-treated groups. (2) No significant differences were detected in the mitochondrial area ratio among the three groups. (3) Cysteine aspartic acid-specific protease 3 (Caspase3) activity and the Bcl-2-associated X protein (bax)/B-cell lymphoma-2 (bcl2) ratio were not higher in the TS2 and TS4 groups compared to the control group. (4) dynamin-related protein 1 (DRP1) protein expression was increased, while mitochondrial fission factor (MFF) protein levels were decreased in the TS2 and TS4 groups compared to the control, suggesting stable mitochondrial fission. (5) No significant differences were observed in the optic atrophy 1 (OPA1), mitofusin 1 and 2 (MFN1 and MFN2) protein expression levels across the three groups. (6) Mitochondrial autophagy vesicles were present in the TS2 and TS4 groups, with a significant increase in Parkin phosphorylation corresponding to the duration of the TS treatment. (7) ATP synthase and citrate synthase activities were significantly elevated in the TS2 group compared to the control group but were significantly reduced in the TS4 group compared to the TS2 group. In summary, the coordinated regulation of apoptosis, mitochondrial fission and fusion, and particularly mitochondrial autophagy preserved mitochondrial morphology and contributed to the restoration of the activities of these two key mitochondrial enzymes, thereby maintaining liver mitochondrial homeostasis in mice under TS conditions.

Unveiling the Interplay: Antioxidant Enzyme Polymorphisms and Oxidative Stress in Preterm Neonatal Renal and Hepatic Functions.

To explore the relationship between oxidative stress biomarkers and the occurrence of acute kidney injury (AKI) alongside notable liver function disturbances in preterm neonates. Given the immaturity of kidneys and incomplete liver development in preterm neonates, oxidative stress poses a considerable threat to their renal and hepatic health. To find out the association between various oxidative stress biomarkers and polymorphisms of antioxidant enzymes with renal and live functions. In this cross-sectional study, we gathered umbilical cord blood and peripheral blood samples for assessing oxidative stress biomarkers and identifying single nucleotide polymorphisms (SNPs) in antioxidant enzymes. Utilizing enzyme-linked immunosorbent assay kits, we quantified these oxidative stress biomarkers. Receiver-operating characteristics curve analysis was employed to ascertain the predictive capacity of these biomarkers, denoted by the area-under-the-curve (AUC). Our findings revealed that umbilical cord heat-shock proteins emerged as robust predictors of neonatal AKI (AUC: 0.92; 95% CI: 0.8-1) with a defined cut-off concentration of 1.8 ng/mL. Likewise, umbilical cord 8-hydroxy-2-deoxy guanosine demonstrated significant predictability for liver function alterations (AUC: 0.7; 95% CI: 0.6-0.9) at a cut-off concentration of 2487.6 pg/mL. We observed significant associations between SNPs in endothelial nitric oxide synthase and catalase with both AKI and impaired liver functions. Prospective studies are warranted to validate these findings, with a particular focus on exploring potential antioxidant interventions aimed at mitigating AKI and liver function abnormalities.

Hepatoprotective effects of vildagliptin mitigates lung biochemical and histopathological changes in experimental hepatopulmonary syndrome model in rat

Hepatopulmonary syndrome (HPS) is a liver disease-induced pulmonary complication manifested with arterial hypoxemia. Hepatic cholestasis, encountered in several clinical situations, leads to biliary cirrhosis and HPS, both of which are best reproduced by rat common bile duct ligation (CBDL). Experience from liver transplantation suggests hepatoprotective-based therapy would be most effective in HPS treatment Dipeptidyl peptidase-4 (DPP-4) enzyme is involved in different pathogenic mechanisms of liver diseases. Vildagliptin (Vild) is a DPP-4 inhibitor which possesses favorable anti-inflammatory, anti-oxidant and anti-fibrotic effects. The present work explored hepatoprotective mechanisms of Vild and their participation in its prophylactic effectiveness in HPS induced by CBDL in rats. Male Wistar rats weighing 220–280 g were allocated into 4 groups: normal control, sham, CBDL and CBDL + Vild groups. i.p. saline was administered to the first 3 groups and i.p. Vild (10 mg/kg/day) was given to the fourth group for 6 weeks starting 2 week before CBDL. CBDL produced liver fibrosis, arterial hypoxemia and decreased survivability of rats. It altered liver functions and induced oxidative stress, pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)], vasodilatory molecules [endothelin-1 (ET-1), and inducible and endothelial nitric oxide synthases] and angiogenesis-associated protein [vascular endothelial growth factor-A (VEGF-A)] in liver and lung. Vild ameliorated liver fibrosis, and improved hypoxemia and survivability of CBDL rats and reversed these biochemical alterations. Prophylactic Vild administration attenuated CBDL-induced HPS in rats via direct hepatoprotective effects in the form of anti-oxidant, anti-inflammatory, anti-angiogenic and anti-fibrotic effects beside inhibition of pathological intrahepatic vasodilatation.

Postoperative early laboratory changes and follow-up process of patients underwent hyperthermic intrathoracic chemotherapy

BackgroundThe aim of combining hyperthermic intrathoracic chemotherapy (HITHOC) with surgery is to achieve local control in patients with pleural malignancies. Liver and kidney dysfunction resulting from this procedure have been reported in the literature. The objective of the study is to examine whether the laboratory abnormalities observed during the initial period persist until day 30.MethodsThe study conducted a retrospective analysis of the blood glucose levels, renal function markers, and hepatic function markers of 30 patients who underwent pleurectomy-decortication and HITHOC for pleural mesothelioma from January 2010 to April 2022. The measurements were taken in the postoperative period on the first four and 30th days. The study analyzed the initial and final laboratory results caused by the procedure.ResultsOut of the total of 30 patients, 29, 28, 14, and 12 patients had elevated glucose levels on the first four days after the surgery, respectively. There was no association between glucose abnormalities and preoperative-postoperative diabetes mellitus. A minority of patients experienced atypical alterations in kidney and liver functions during the initial postoperative period. There was no apparent relationship between the renal and hepatic functions in the early and late periods after the surgery.ConclusionAlthough there were fluctuations in glucose levels and renal and hepatic functions in the early period after surgery, there were no persistent alterations in these parameters by day 30. Elevated glucose levels during the early period were not associated with the development of newly diagnosed diabetes mellitus after surgery. The findings of our study provide evidence that HITHOC is a favorable and well-tolerated treatment option for mesothelioma.

Obesity as Inducer of Cognitive Function Decline via Dysbiosis of Gut Microbiota in Rats.

Diet-induced obesity is a global phenomenon that affects the population worldwide with manifestations at both the phenotypic and genotypic levels. Cognitive function decline is a major global health challenge. The relation between obesity and cognitive function is a debatable issue. The main goal of the current research was to study the implications of obesity on cognitive function and gut microbiota diversity and its impact on plasma and brain metabolic parameters in rats. Obesity was induced in rats by feeding on a high-fat (HF) or a high-fat/high-sucrose (HFHS) diet. The results reveal that both the HF (0.683) and HFHS (0.688) diets were effective as obesity inducers, which was confirmed by a significant increase in the body mass index (BMI). Both diet groups showed dyslipidemia and elevation of oxidative stress, insulin resistance (IR), and inflammatory markers with alterations in liver and kidney functions. Obesity led to a reduction in cognitive function through a reduction in short-term memory by 23.8% and 30.7% in the rats fed HF and HFHS diets, respectively, and learning capacity and visuo-spatial memory reduced by 8.9 and 9.7 s in the rats fed an HF or HFHS diet, respectively. Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Spirochaetes phyla were detected. The Firmicutes/Bacteroidetes ratio (F/B) significantly decreased in the HF group, while it increased in the HFHS group compared to the normal control. The two species, Bacteroides acidifaciens and Bacteroides ovatus, which are associated with IR, were drastically compromised by the high-fat/high-sucrose diet. Some species that have been linked to reduced inflammation showed a sharp decrease in the HFHS group, while Prevotella copri, which is linked to carbohydrate metabolism, was highly enriched. In conclusion: Obesity led to cognitive impairment through changes in short-term and visuo-spatial memory. A metagenomic analysis revealed alterations in the abundance of some microbial taxa associated with obesity, inflammation, and insulin resistance in the HF and HFHS groups.

Phytogenic effects of Marrubium vulgare on the growth performance of weaned piglets: biochemical parameters and liquid chromatographic-electrospray ionization-mass spectrometric profile of plant and animal serum.

Multidrug-resistant bacteria in humans have prompted the search for alternative solutions derived from herbal medicines that can substitute antibiotics in livestock production. Thus, the goal of this study was to evaluate the phytogenic properties of Marrubium vulgare infusion (MVI) on weaned pigs. Thirty animals were randomly divided into five groups of six animals, each receiving a physiological solution, clenbuterol and the infusion extract at doses of 0.01 (MVI 1%), 0.1 (MVI 10%) and 0.2 (MVI 20%) mg kg-1 for 28 days. Biochemical parameters and the liquid chromatographic-electrospray ionization-mass spectrometric (LC-ESI-MS) chemical profiles of the infusion extract and animal serum were studied. The doses MVI 1 and 10% led to weight gain higher than the controls. No significant changes were noted in the biochemical parameters including erythrocytes, hemoglobin, hematocrit, mean corpuscular volume and others. Evaluation of enzymatic levels in blood revealed no significant changes. LC-ESI-MS data of MVI showed the presence of 34 secondary metabolites, and successive chromatographic purification of MVI yielded marrubiin and apigenin as major components. LC-ESI-MS data of animal serum showed the presence of a diterpene, a flavonoid and diverse cholic acid derivatives. Results indicated the doses MVI 1 and 10% promote weight gain with no significant alterations in blood biochemicals, and liver and kidney function. © 2024 Society of Chemical Industry.

Intestinal Dysbacteriosis Contributes to Persistent Cognitive Impairment after Resolution of Acute Liver Failure

Regulating the gut microbiota alleviates hepatic encephalopathy (HE). It remains unclear whether it is imperative to withhold treatment for microbial imbalance after liver functional recovery. The aim of this work was to elucidate the alterations in cognitive behavior, liver function, synaptic transmission, and brain metabolites in acute liver failure (ALF) mice before and after hepatic function recovery. In this study, thioacetamide was injected intraperitoneally to establish an ALF mouse model, which induced HE. By performing hierarchical clustering analysis, we showed that the liver functions normalized, but cognitive dysfunction and intestinal dysbacteriosis were found in the ALF mice 14 days after thioacetamide injection. In addition, fecal microbiota transplantation from the ALF mice with liver function recovery could induce liver injury and cognitive impairment. Moreover, alterations in synaptic transmission were found in the ALF mice with liver function improvement, and the correlations between the gut bacteria and synaptic transmission in the cortex were significant. Finally, we detected apparent alterations in the brain metabolic profiles of the ALF mice after liver function improvement by performing 1H nuclear magnetic resonance spectroscopy, suggesting a risk of HE. These results show that intestinal dysbacteriosis in ALF mice with liver function recovery is sufficient to induce liver injury and cognitive impairment. These results indicate that continuous care may be necessary for monitoring microbial imbalance even in patients with ALF-induced HE whose liver function has recovered significantly.

Development of a biodegradable prosthesis through tissue engineering, for the organ-replacement or substitution of the extrahepatic bile duct

Introduction and ObjectivesThere are different situations in which an extrahepatic bile duct replacement or substitute is needed, such as initial and localized stages of bile duct cancer, agenesis, stenosis, or bile duct disruption. Materials and MethodsA prosthesis obtained by electrospinning composed of Poly (D,L-lactide-co-glycolide) (PGLA) - Polycaprolactone (PCL) - Gelatin (Gel) was developed, mechanical and biological tests were carried out to evaluate resistance to tension, biocompatibility, biodegradability, cytotoxicity, morphological analysis and cell culture. The obtained prosthesis was placed in the extrahepatic bile duct of 15 pigs with a 2-year follow-up. Liver function tests and cholangioscopy were evaluated during follow-up. ResultsMechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable. The prosthesis implanted in the experimental model allowed cell adhesion, migration, and proliferation, maintaining bile duct permeability without altering liver function tests. Immunohistochemical analysis indicates the presence of biliary epithelium. ConclusionsA tubular scaffold composed of electrospun PGLA-PCL-Gel nanofibers was used for the first time to replace the extrahepatic bile duct in pigs. Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable, making it an excellent candidate for use in bile ducts and potentially in other tissue engineering applications.

Medical complications among acute leukaemia patients receiving inward induction chemotherapy at haematooncology section of the National Cancer Institute, Sri Lanka

Introduction: Acute leukaemias are complicated with numerous disease and treatment related medical complications. Infection is one of the major complications and is related to chemotherapy associated-neutropaenia. This study aims to identify medical complications in acute leukaemia patients during the induction chemotherapy period. Results: Medical complications were observed in patients receiving induction chemotherapy N=50. Infections and electrolyte disturbances were the most frequently observed complications (74% each) followed by chemotherapy induced neutropaenia (38%), alteration of liver functions (32%), steroid induced hyperglycaemia (28%) and bleeding (16%). Thrombosis and tumour lysis were detected at lesser frequencies (4% each). Among infections, the majority showed evidence of blood stream infection (27%) followed by pulmonary infections (24.3%). Gram negative organisms were the most frequently identified pathogen. Among the electrolyte disturbances, hypokalaemia (48%), hyponatraemia (48%), and hypocalcaemia (44%) were more prevalent. Mean duration from initiation of chemotherapy to neutrophil nadir was 10.05 days.Conclusions: Patients with acute leukaemia encounter a multitude of disease and treatment related medical complications during induction chemotherapy. Infection is the most common complication with higher rates of bacteraemia and gram-negative sepsis. This is likely to be a result of treatment related neutropaenia. However, further focused studies on neutropaenic sepsis during induction chemotherapy are recommended. Clinical vigilance, strict and improved infection control strategies are necessary to improve the outcome of these patients.

Acetaldehyde and Butyrate: Their Biological Effects on the Liver and the Gut Axis

Abstract: The gut is the most accommodating environment in the human body for bacteria. The microbial community there is both dense and varied. The gut microbe forms an axis with the human liver, according to the theory of liver disease causation. The portal vein, systemic circulation, and biliary tract all provide bidirectional connections between the liver and the intestines. The liver secretes bile acid and a wide variety of bioactive mediators into the biliary tract and general circulation. : On the other hand, the portal vein carries microbial-produced endogenous compounds from the colon to the liver, where they might disrupt liver function. Acetyl-aldehyde and butyrate are two of the many byproducts produced by the microbiota in the human gut in response to indigestible food. In addition, these two waste products alter liver function and play an important role in maintaining intestinal health in humans. This paper reviews the literature on the link between butyrate and acetyl-aldehyde production in the human gut and the organ's role in the development of liver disease. Butyrate, acetyl-aldehyde, and liver disease all play roles in the gut-liver axis.

Approach to the patient with abnormal liver biochemistry

Altered liver function tests are a common finding that requires careful interpretation and thorough correlation with the patient's clinical picture. This paper provides a systematic and practical approach to the management of patients with alterations in their liver biochemistry. The fundamental concepts of liver anatomy and physiology are reviewed, emphasizing the importance of understanding the microscopic organization of the organ and key metabolic processes. The most used liver tests, their interpretation and the patterns of alterations that may occur will be described, and the importance of a detailed anamnesis will be emphasized. Guidelines are provided for the diagnostic approach according to the pattern of alteration observed and the different patterns of transaminase elevation, from mild to moderate and severe, and their possible causes are discussed in detail. The importance of considering fatty liver disease as a frequent cause of mild and persistent transaminase elevations is highlighted, and noninvasive tools for the evaluation of liver fibrosis, such as specialized scores and markers, are mentioned. In summary, this document presents an updated and practical text for the proper interpretation of alterations in liver biochemistry, emphasizing the importance of a close correlation with the clinical context of the patient, which will allow an accurate diagnosis and appropriate management.

Monascus red pigments alleviate high-fat and high-sugar diet-induced NAFLD in mice by modulating the gut microbiota and metabolites.

Monascus red pigments (MRP) may have benefits against NAFLD with an unclear mechanism. This study aimed to explore the protective effect of MRP supplementation against NAFLD through regulation of gut microbiota and metabolites. The C57BL/6 mice animals were randomly allocated into the normal diet (NC), HFHS diet-induced NAFLD model, and MRP intervention group fed with HFHS diet. Serum lipid profiles and liver function parameters were measured. Liver and colon histopathology analysis was conducted to determine the injury in the liver and colon. 16S rRNA gene sequencing was employed to analyze gut microbial composition from fecal samples. Untargeted metabonomics was performed to analyze changes in metabolites in serum and fecal samples. MRP supplementation significantly improved the HFHS-induced alterations in body weight, lipid profiles, and liver function (p < .01). MRP supplementation decreased the abundance of Akkermansia, Candidatus saccharimonas, Dubosiella, and Oscillibacter, while increasing Lactobacillus, Lachnospiraceae NK4A136 group, and Rikenella in mice fed the HFHS diet. Furthermore, MRP supplementation improved the serum and fecal metabolic profiles induced by the HFHS diet, primarily involving the arachidonic acid metabolism, unsaturated fatty acid biosynthesis, and adipocyte lipolysis pathways. Liver function and lipid profiles were closely associated with the abundance of Lactobacillus, Streptococcus, Oscillibacter, Akkemansia, and Desulfovibrio (p < .01). These findings revealed that MRP supplementation may help restore gut microbiota composition and balance its metabolites, thereby improving NAFLD. This study presents a novel outlook on the potential benefits of MRP supplementation in ameliorating NAFLD and supports the application of MRP as a new functional food.

Comparative Study of Levels of Serum Bilirubin, Serum Transaminase, Serum Alkaline Phosphatase, and Prothrombin Time After Laparoscopic Cholecystectomy and Open Cholecystectomy.

Laparoscopic cholecystectomy (LC) is universally accepted as the gold standard treatment for symptomatic gallstones. However, it has some drawbacks. Some of the major drawbacks of LC include increased bile duct injuries and longer operation time. Furthermore, it may cause changes in the body systems, such as alterations in acid-base, pulmonary status, cardiovascular system, and liver function. Thus far, no causes for these changes have been identified. This study aimed to evaluate the effect of laparoscopic and open cholecystectomy on liver enzymes, prothrombin time (PT), and serum bilirubin. In the current study, we found significant increases in aspartate transferase (AST), alanine transaminase (ALT), and total bilirubin, on day 1 and day 3 after LC but no significant change in alkaline phosphatase (ALKP) and PT.It is important for surgeons to know about these transient changes in the immediate postoperative period to avoid misdiagnosis and adopt proper treatment and management.

Presencia de eimerias en alpacas destetadas y alternativa de control sin ocasionar daño hepático

Considerando que la eimeriosis en alpacas es una enfermedad mortal, se plantea el objetivo de brindar una alternativa profiláctica en alpacas destetadas. Se evaluaron 30 alpacas del CICAS “La Raya” Cusco en Agosto 2022, distribuidas en 3 grupos de 10 alpacas, grupo1 (G1) 15 mg/kpv, grupo2 (G2) 22,5 mg/kpv de Toltrazuril y grupo3 (G3) control. Se realizó análisis coproparasitológico cualitativo de concentración por flotación y cuantitativo mediante método de McMaster modificado pre y post tratamiento; un posible daño hepático se evidenció mediante niveles séricos de alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). Como resultados, se identificaron eimerias en el 93,33% de alpacas destetadas, siendo más prevalente E. macusaniensis (63,33%). Así mismo, Toltrazuril a 22,5 mg/kpv controla parcialmente E. macusaniensis, mientras que a 15 y 22,5 mg/kpv controlan efectivamente a E. lamae a los 14 días post tratamiento; los niveles de AST y ALT en alpacas con 22,5 mg/kpv de Toltrazuril fueron 5,7 UI/L y 195,8 UI/L, respectivamente. En conclusión, Toltrazuril logra controlar a eimerias patógenas en alpacas, de manera parcial a E. macusaniensis, pero de forma efectiva a eimerias pequeñas como E. lamae sin alterar la función hepática en alpacas destetadas.

Living tape worms in the duodenal lumen: A rare case report

Fascioliasis is an infection caused by a trematode of the liver, Fasciola hepatica, which affects sheep, goats and cattle. Humans become accidental hosts through drinking contaminated water or ingesting raw green vegetables that has been contaminated with encysted metacercariae, which is the infective form. Fascioliasis has a hepatic phase and a biliary phase, each displaying different clinical signs and symptoms. Common signs and symptoms of the hepatic phase are abdominal pain, fever, eosinophilia, and abnormal liver function tests. The biliary phase of the disease usually presents with intermittent right upper quadrant pain with or without cholangitis or cholestasis. However, it is very rare to find a living flukes in the common bile duct (CBD) and duodenal lumen as it usually lives in gall-bladder and smaller biliary tracts. Here we report a case of human infestation of Fasciola hepatica, who presented with respiratory tract infection with abdominal pain &amp; dyspeptic symptoms and eventually during evaluation, an upper gastro-intestinal endoscopy revealed several flat worms at the second part of the duodenum. The worms were sent to microbiology department for identification. The organisms were confirmed to be Fasciola hepatica. The patient was given tablet Nitazoxanide 500mg 12 hourly for 7 days. The symptoms reduced in intensity after two days of nitazoxanide. The patient was then discharged with an advice of a stool routine examination after one month of completion of nitazoxanide. As fasciolosis is non endemic in our country, a high degree of suspicion is required to ensure early detection and management of such cases. Patients with abdominal pain, altered liver function tests &amp; eosinophilia should always be evaluated for a suspected Fasciola hepatica infection and should be kept as a differential in these cases. Bangladesh Crit Care J March 2024; 12 (1): 54-57

Features of clinical and laboratory manifestations of moderate-to-severe COVID-19 in male and female inpatients

The article presents results of a study of the moderate to severe coronavirus infection COVID-19 in male and female male and female hospitalized inpatients. It has been shown that in hospitalized men with moderate to severe coronavirus infection there are more pronounced manifestations of the common inflammatory reaction such as hyperthermia (p&lt;0,05), neutrophilic leukocytosis(p&lt;0,05), and CRP-elevation(p&lt;0,05). Kidney damage was more severe in men than in women initially (p&lt;0,05) and after treatment (p&lt;0,05). Alterations in liver function of male patients were observed at initiation and post-treatment, while female patients only developed such nearing the end of hospitalization.

O255: Is a low calorie "liver shrinking" diet predictive of long term weight loss and metabolic improvement after sleeve gastrectomy?

Abstract Introduction Limited evidence exists regarding pre-operative “liver shrinking” diet, but a two-week period of low calorie diet (LCD) is mandated before bariatric surgery, with weight outcomes rarely measured. Longer periods of LCD can ameliorate obesity, diabetes and metabolic-associated-fatty-liver disease (MAFLD). Primary aim to determine if response to LCD is predictive of long-term weight loss. Secondary aim to determine if alteration in liver function, and MAFLD, correlate with weight change after diet/ in follow up. Methodology Patients undergoing sleeve gastrectomy recruited and weight, blood plasma and 16S rRNA faecal microbiome profile recorded at baseline, following two-week LCD and at six-months, with liver biopsy at surgery (6). Results First nine patients had median baseline BMI 47.3kg/m2, and 34.7 kg/m2 at 6-months (-12.3kg/m2). Median excess weight loss was 8.6% (6.35kg) after LCD and 47.57% (34.65kg) at 6-months. Spearman’s Rank Correlation was weakly positive (0.5) for absolute weight loss between LCD and follow up, and was 0.25 using excess weight loss (non-significant). Change in liver function and MAFLD grade did not correlate with weight loss following LCD and at 6-months. Conclusions Weight loss response to LCD correlated poorly with long-term weight loss (analysing by absolute/ excess weight). Liver health and MAFLD did not predict 6-month weight loss. A dramatic response to LCD may not manifest in longer term metabolic improvement after surgery. We will also report on faecal microbiome; it appears more complex mechanisms underpin weight change and response to dietary manipulation in the surgical cohort than can be extrapolated from population studies.

Tumor-activated IL-2 mRNA delivered by lipid nanoparticles for cancer immunotherapy

Interleukin-2 (IL-2) exhibits the unique capacity to modulate immune functions, potentially exerting antitumor effects by stimulating immune responses, making it highly promising for immunotherapy. However, the clinical use of recombinant IL-2 protein faces significant limitations due to its short half-life and systemic toxicity. To overcome these challenges and fully exploit IL-2's potential in tumor immunotherapy, this study reports the development of a tumor-activated IL-2 mRNA, delivered via lipid nanoparticles (LNPs). Initially, ionizable lipid U-101 derived nanoparticles (U-101-LNP) were prepared using microfluidic technology. Subsequent in vitro and in vivo delivery tests demonstrated that U-101-LNP achieved more effective transfection than the approved ALC-0315-LNP. Following this, IL-2F mRNAs, encoding fusion proteins comprising IL-2, a linker, and CD25 (IL-2Rα), were designed and synthesized through in vitro transcription. A cleavable linker, consisting of the peptide sequence SGRSEN↓IRTA, was selected for cleavage by matrix metalloproteinase-14 (MMP-14). IL-2F mRNA was then encapsulated in U-101-LNP to create U-101-LNP/IL-2F mRNA complexes. After optimization, assessments of expression efficiency, masking, and release characteristics revealed that IL-2F with linker C4 demonstrated superior performance. Finally, the antitumor activity of IL-2F mRNA was evaluated. The results indicated that U-101-LNP/IL-2F mRNA achieved the strongest antitumor effect, with an inhibition rate of 70.3%. Immunohistochemistry observations revealed significant expressions of IL-2, IFN-γ, and CD8, suggesting an up-regulation of immunomodulation in tumor tissues. This effect could be ascribed to the expression of IL-2F, followed by the cleavage of the linker under the action of MMP-14 in tumor tissue, which sustainably releases IL-2. H&E staining of tissues treated with U-101-LNP/IL-2F mRNA showed no abnormalities. Further evaluations indicated that the U-101-LNP/IL-2F mRNA group maintained proper levels of inflammatory factors without obvious alterations in liver and renal functions. Taken together, the U-101-LNP/IL-2F mRNA formulation demonstrated effective antitumor activity and safety, which suggests potential applicability in clinical immunotherapy.