Hepatic Impairment Research Articles

Low-dose colchicine for atherosclerosis: long-term safety.

Low-dose colchicine (0.5 mg daily) is now FDA-approved for secondary prevention in patients with coronary disease and will be increasingly prescribed in clinical practice. In this State-of-the-Art Review, data were collated from contemporary systemic reviews of case reports, drug registries, and placebo-controlled trials that assessed specific issues of safety related to the continuous use of colchicine in a range of clinical settings to inform physicians, pharmacists, and patients of the absolute risks of continuous use of low-dose colchicine, including among individuals taking statin therapy. Based upon these collective data, it is concluded that aside mild diarrhoea on initiation of colchicine that typically subsides in the vast majority of patients within a week of therapy, continuous use of low-dose colchicine is well tolerated and very safe. It does not affect renal, liver, or cognitive function, has no adverse effects on bleeding, wound healing, fertility, or pregnancy, and does not increase risks of cancer, serious infection, or cause-specific mortality. When appropriately prescribed to patients without significant renal or hepatic impairment, reports of myelosuppression, myotoxicity, and serious drug-drug interactions are rare and no more frequent than placebo, including in patients taking statin therapy. Physicians, pharmacists, and patients can be reassured that in the absence of significant renal or hepatic impairment continuous use of low-dose colchicine can be used safely in patients with atherosclerosis for the purpose of reducing cardiovascular risk.

No Clinically Relevant Effects of Hepatic Impairment on the Pharmacokinetics of a Next Generation Prodrug Troriluzole (P4-4.014)

No Clinically Relevant Effects of Hepatic Impairment on the Pharmacokinetics of a Next Generation Prodrug Troriluzole (P4-4.014)

Hepatitis B virus-specific human stem cell memory T cells differentiate into cytotoxic T cells and eradicate HBV-infected hepatocytes in mice.

Chronic infection with the hepatitis B virus (HBV) induces progressive hepatic impairment. Achieving complete eradication of the virus remains a formidable challenge. Cytotoxic T lymphocytes, specific to viral antigens, either exhibit a numerical deficiency or succumb to an exhausted state in individuals chronically afflicted with HBV. The comprehension of the genesis and dissemination of stem cell memory T cells (TSCMs) targeting HBV remains inadequately elucidated. We identified TSCMs in subjects with chronic HBV infection and scrutinized their efficacy in a murine model with human hepatocyte transplants, specifically the TK-NOG mice. TSCMs were discerned in all subjects under examination. Introduction of TSCMs into the HBV mouse model precipitated a severe necro-inflammatory response, resulting in the elimination of human hepatocytes. TSCMs may constitute a valuable tool in the pursuit of a remedial therapy for HBV infection.

A Study on the Clinical Profile of Non-Organophosphorus Poisoning in a Tertiary Care Hospital

Poisoning is emerging as a very important global health issue particularly in agricultural countries like India. Although wide range of data is available on organophosphorus poisoning cases, studies and data are limited on non-organophosphorus compound poisoning like paraquat, rodenticide (zinc phosphide, yellow phosphorus, sodium monofluroacetate, fluroacetamide, arsenic, warfarins, and scilliroside etc.), pyrethroid, carbamate etc. The present study aims to study the clinical presentation and outcome of the non-organophosphorus poisoning cases. A cross sectional retrospective study was conducted at Assam Medical College and Hospital, Dibrugarh. In this study the data of the patients with nonorganophosphorus poisoning admitted to Assam Medical College from July, 2022 to July, 2023 were collected and analysed. A total of 104 patients were included in the study and most patients belonged to the age group of below 30 years. Out of all the cases highest number patients presented with Paraquat poisoning (48.1%), while distribution of other cases was as follows- Phenyl (12.5%), Pyrethroid (23.1%), Rodenticide (10.6%), Carbamate (1.9%) and Organochloride (3.6%). Vomiting was the most common presenting symptom. Hepatic and renal impairment was observed only in the paraquat poisoning cases and it was also associated with high mortality rate (88%). Acute Hepatitis and Acute kidney Injury was quite common among paraquat poisoning patients and mortality was mainly observed in paraquat, rodenticide and carbamate poisoning cases. Comprehensive care and awareness among general public is necessary for prevention and better management of poisoning cases. Development of proper rational management guidelines is also pivotal for reducing mortality in these cases.

Isoflurane, like sepsis, decreases CYP1A2 liver enzyme activity in intensive care patients: a clinical study and network model.

Liver function of intensive care patients is routinely monitored by static blood pathology. For specific indications, liver specific cytochrome activity may be measured by the commercially available maximum liver function capacity (LiMAx) test via quantification of the cytochrome P450 1A2 (CYP1A2) dependent C-methacetin metabolism. Sedation with the volatile anesthetic isoflurane was suspected to abrogate the correlation of LiMAx test with global liver function. We hypothesized that isoflurane has a CYP1A2-activity and LiMAx test result decreasing effect. In this monocentric, observational clinical study previously liver healthy intensive care patients, scheduled to be changed from propofol to isoflurane sedation, were enrolled. LiMAx testing was done before, during and after termination of isoflurane sedation. The mean LiMAx value decreased during isoflurane sedation. Septic patients (n = 11) exhibited lower LiMAx values compared to non-septic patients (n = 11) at all time points. LiMAx values decreased with isoflurane from 140 ± 82 to 30 ± 34 µg kg-1 h-1 in the septic group and from 253 ± 92 to 147 ± 131 µg kg-1 h-1 in the non-septic group while laboratory markers did not imply significant hepatic impairment. Lactate increased during isoflurane inhalation without clinical consequence. Sepsis and isoflurane have independently demonstrated an effect on reducing the hepatic CYP1A2-activity. A network model was constructed that could explain the mechanism through the influence of isoflurane on hypoxia inducible factor (HIF-1α) by upregulation of the hypoxia-inducible pathway and the downregulation of CYP1A2-activity via the ligand-inducible pathway. Thus, the increased anaerobic metabolism may result in lactate accumulation. The influence of isoflurane sedation on the validated correlation of global liver function with CYP1A2-activity measured by LiMAx testing needs to be investigated in more detail.

Cholinergic anti-inflammatory pathway confers protective effects in septic shock rats

Background: Septic shock can lead to multiple organ dysfunction. The cholinergic anti-inflammatory pathway is known to prevent organ damage from infection by modulating the inflammatory response. However, the modulatory capacity of cholinergic anti-inflammatory pathways in septic shock remains unclear. Methods: Cecal ligation and puncture (CLP) was used to establish a rat model of septic shock. Bilateral cervical vagal nerve isolation, dual cervical vagotomy, and vagus nerve stimulation (VNS) were used to inhibit or activate cholinergic anti-inflammatory pathways. Tacrine and α-bungarotoxin groups were used to mimic the activation and shutdown of cholinergic anti-inflammatory pathways. The survival status, hemodynamic indicators, inflammatory cytokine content, and inflammatory response of liver and kidney tissues of the rats were detected. Results: Dual cervical vagotomy significantly exacerbated the hepatic (p < 0.05) and renal (p < 0.05) impairment in septic shock rats relative to the sham-operated group. Tacrine, a cholinergic potentiator, significantly alleviated liver (p < 0.05) and kidney (p < 0.05) damage in septic shock rats. Dual cervical vagotomy significantly promoted the expression of pro-inflammatory factors caused by septic shock in rat liver and kidney tissues (p < 0.05), while Tacrine treatment inhibited the increase of inflammatory factors (p < 0.05). Conclusions: Activation of the cholinergic anti-inflammatory pathway exerts protective effects on multiple organ dysfunction caused by septic shock. The cholinergic enhancer, Tacrine, and VNS effectively ameliorated liver and kidney damage, improved hemodynamic indicators, and enhanced survival rates in septic shock rats.

Cytomegalovirus colitis as intestinal obstruction in an immunocompetent adolescent: a case report and literature review

BackgroundCytomegalovirus infection manifests varying clinical characteristics and severity in diverse populations with different immune statuses. The signs and symptoms of gastrointestinal involvement are nonspecific. Here, we present a case of cytomegalovirus colitis in an immunocompetent adolescent, which manifested as intestinal pseud-obstruction.Case presentationA 15-year-old man who had contracted novel coronavirus infection one month earlier was admitted to our hospital with fever, abdominal pain, and hematochezia. His abdomen was distended, and laboratory evaluation revealed a decrease in the blood count, an increase in inflammatory indicators and hepatic impairment. Imaging shows bowel wall thickening and dilatation of the colon. A diagnosis of intestinal infection combined with acute intestinal pseud-obstruction was made. Diarrhea persisted despite conservative treatment with empirical antibiotics. A colonoscopy was performed. Pathology confirmed cytomegalovirus infection. Ganciclovir therapy was initiated, and subsequent review showed a good recovery.ConclusionsThe case was diagnosed as cytomegalovirus colitis. We reviewed the reports of 9 cases of bowel obstruction, including our own, and found that the majority of the adult patients were elderly with underlying disease. Clinical and endoscopic manifestations are typically nonspecific, and imaging shows typical signs of intestinal obstruction. The final diagnosis was confirmed by pathology. Most of them have a good prognosis. We suggest that cytomegalovirus colitis can also lead to intestinal obstruction and that viral reactivation in immunocompetent individuals may be associated with inflammatory conditions and viral coinfection, particularly with the novel coronavirus.

CBD and THC in Special Populations: Pharmacokinetics and Drug-Drug Interactions.

Cannabinoid use has surged in the past decade, with a growing interest in expanding cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) applications into special populations. Consequently, the increased use of CBD and THC raises the risk of drug-drug interactions (DDIs). Nevertheless, DDIs for cannabinoids, especially in special populations, remain inadequately investigated. While some clinical trials have explored DDIs between therapeutic drugs like antiepileptic drugs and CBD/THC, more potential interactions remain to be examined. This review summarizes the published studies on CBD and THC-drug interactions, outlines the mechanisms involved, discusses the physiological considerations in pharmacokinetics (PK) and DDI studies in special populations (including pregnant and lactating women, pediatrics, older adults, patients with hepatic or renal impairments, and others), and presents modeling approaches that can describe the DDIs associated with CBD and THC in special populations. The PK of CBD and THC in special populations remain poorly characterized, with limited studies investigating DDIs involving CBD/THC in these populations. Therefore, it is critical to evaluate potential DDIs between CBD/THC and medications that are commonly used in special populations. Modeling approaches can aid in understanding these interactions.

Clinical Pharmacology of the Antibody-Drug Conjugate Enfortumab Vedotin in Advanced Urothelial Carcinoma and Other Malignant Solid Tumors.

Enfortumab vedotin is an antibody-drug conjugate comprised of a human monoclonal antibody directed to Nectin-4 and monomethyl auristatin E (MMAE), a microtubule-disrupting agent. The objectives of this review are to summarize the clinical pharmacology of enfortumab vedotin monotherapy and demonstrate that the appropriate dose has been selected for clinical use. Pharmacokinetics (PK) of enfortumab vedotin (antibody-drug conjugate and total antibody) and free MMAE were evaluated in five clinical trials of patients with locally advanced or metastatic urothelial carcinoma (n=748). Intravenous enfortumab vedotin 0.5-1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle showed linear, dose-proportional PK. No significant differences in exposure or safety of enfortumab vedotin and free MMAE were observed in mild, moderate, or severe renal impairment versus normal renal function. Patients with mildly impaired versus normal hepatic function had a 37% increase in area under the concentration-time curve (0-28 days), a 31% increase in maximum concentration of free MMAE, and a similar adverse event profile. No clinically significant PK differences were observed based on race/ethnicity with weight-based dosing, and no clinically meaningful QT prolongation was observed. Concomitant use with dual P-glycoprotein and strong cytochrome P450 3A4 inhibitors may increase MMAE exposure and the risk of adverse events. Approximately 3% of patients developed antitherapeutic antibodies against enfortumab vedotin 1.25 mg/kg. These findings support enfortumab vedotin 1.25 mg/kg monotherapy on days 1, 8, and 15 of a 28-day cycle. No dose adjustments are required for patients with renal impairment or mild hepatic impairment, or by race/ethnicity.

Aprocitentan (TRYVIO)

Abstract Aprocitentan (TRYVIO), is the first and only endothelin receptor antagonist for the treatment of high blood pressure not adequately controlled in combination with 3 combined antihypertensive class drugs. Aprocitentan is a dual endothelin receptor antagonist that inhibits the binding of ET-1 to both ETA and ETB receptors. Aprocitentan tablets are available as 12.5 mg orally once daily. It can be administered to subjects with mild and moderate hepatic impairment without the need for dose adjustment. The most frequently reported adverse reactions to during the 4-week double blind placebo-controlled treatment period (part 1) of the PRECISION study is edema and anaemia. Others include embryo-fetal toxicity, hepatotoxicity, fluid retention, hemoglobin decrease, decreased sperm counts. Aprocitentan is contraindicated in pregnancy and in patients who are hypersensitive to aprocitentan or any of its excipients.

Proteomics Reveals the Role of Paederia scandens in ameliorating Non-alcoholic Fatty Liver Disease in a Rat Model

This study was conducted to evaluate the effect of Paederia scandens on high-fat diet­induced non-alcoholic fatty liver disease (NAFLD) in a rat model and further show the therapeutic mechanisms of Paederia scandens. Thirty rats weighing 180 ± 12 g (6 weeks old) were randomly divided into three groups: A control group (CG), a high-fat diet model group (HF), and a Paederia scandens intervention group (PS). After 45 days, the rats' serum lipid metabolism, liver injury parameters, and liver proteomics were detected. The results indicated that dietary Paederia scandens significantly reduced the levels of triglycerides, total cholesterol, glucose, and low-density lipoprotein cholesterol in the NAFLD rats compared with those in the HF group. Meanwhile, decreased levels of alanine aminotransferase and aspartate transaminase were observed in rats of the PS group. In addition, 382 differentially abundant proteins were identified between the HF and PS groups. Protein-protein interaction network analysis identified 14 keystone proteins that might play critical roles in ameliorating NAFLD. In particular, Paederia scandens treatment significantly upregulated the levels of Hadh, Hadhb, Acadl, Acox1, Acox3, Cyp3a2, and Cyp1a1, which are involved in fatty acid β‑oxidation, PPAR, and cytochrome P450 signaling pathways. Hence, the data demonstrated that Paederia scandens ameliorates hepatic lipid accumulation and impairment by enhancing fatty acid β-oxidation and activating PPAR and cytochrome P450 signaling pathways. These data provide new insights into the treatment of NAFLD and suggest the potential of Paederia scandens as an effective therapy.

Hepatoxicity Induced from Exposure of Male Rats to Low Doses of Tributyltin Chloride

Tributyltin (TBT) is a contaminant found all over the world. It is a member of the organotin class, which includes several widely disseminated, very hazardous compounds that have been linked to endocrine disruption. Consumption of TBT-contaminated seafood and drinking water are the most common routes of exposure among the susceptible population to man at low doses. The main goal of this study is to recognize the hepatotoxicity of low doses of TBT chloride (10-2000 µg/Kg body weight) in male rats for 45 days. TBT significantly induce hepatic impairment of antioxidant systems, oxidative stress, lipid peroxidation, and histological abnormalities in the liver architecture. In conclusion: the TBT at low doses could induce hepatotoxicity at low levels due to its lipophilic properties and the ability for accumulation in tissues.

Ameliorative effect of Quercetin and Omega-3 Fatty Acids on haematological and liver function impairment induced by mosquito coil smoke in male Wistar rats

The use of mosquito coils is one method adopted to control malaria Inhalation of the coil smoke causes adverse effects, including hepatic and haematological toxicities associated with oxidative stress. Therefore, this study investigated the effects of phytochemical antioxidants (Quercetin and Omega-3) on mosquito coil smoke-induced haematological and hepatic impairments. Twenty male Wistar rats were divided into 4 groups viz control, mosquito coil-only (MC), mosquito coil+Quercetin (MC+Q) and mosquito coil+Omega-3 (MC+OM3) groups of five rats each. Quercetin and Omega-3 were administered daily at 20mg/kg and 600mg/kg respectively. The duration of daily exposure and treatment was 42 days after which blood samples were collected via cardiac puncture for determination of relevant haematological and hepatic parameters. The RBC count was significantly reduced in the MC group compared with the control (P<0.05) but was higher in the MC+Quercetin group than in the MC group. Haemoglobin was decreased in the MC and MC+Omega-3 groups compared with the control (P<0.05). White blood cell count was higher in the MC group than in the control group (P<0.05) but lower in the MC+OM3 and MC+Q groups than in the MC group (P<0.05). The lymphocyte count was higher in the MC group than in the control group (P<0.05). Serum aspartate transaminase and alanine transaminase were significantly increased (P<0.05) in the MC group compared with the control group but were reduced (P<0.05) in the MC+OM3 and MC+Q groups compared with the MC group. Serum alkaline phosphatase was significantly higher (P<0.05) in the MC group than in control (P<0.05) but significantly lower (P<0.05) in the MC+OM3 group than in the MC group. Serum total bilirubin was significantly elevated in the MC group compared to that in the control group (P<0.05). The serum concentration of direct bilirubin was significantly higher (P<0.05) in the MC group than in the control group. We conclude that Omega-3 and Quercetin ameliorate haematological and hepatic function impairments in Wistar rats exposed to mosquito coil smoke.

Miliary tuberculosis diagnosed by diffuse hepatic uptake on PET/CT and transjugular liver biopsy.

The patient was an 81-year-old man. In his 20s, he had been treated with pharmacotherapy for pulmonary tuberculosis for 1 year. He presented to the Department of Respiratory Medicine with a chief complaint of dyspnea. The possibility of respiratory disease appeared to be low, but hepatic impairment was detected. The patient was thus referred to our department. Though the cause of hepatic impairment was unknown, the soluble interleukin-2 receptor level was elevated, suggesting malignant lymphoma. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) revealed diffuse, homogenous, intense FDG uptake in the entire liver, and transjugular liver biopsy confirmed the diagnosis. Histopathological examination revealed an epithelioid granuloma, and auramine staining was positive for bacilli suggestive of tuberculosis. CT revealed diffuse micronodular shadows in the lung, yielding a diagnosis of miliary tuberculosis. Therefore, the patient was prescribed antituberculosis medication by the Department of Respiratory Medicine. His subsequent clinical course was good. The miliary (hepatic) tuberculosis was typical based on the diffuse, homogenous, intense FDG uptake throughout the liver observed on PET-CT.

Effect of Hepatic Impairment on the Pharmacokinetics of Fenfluramine and Norfenfluramine.

Fenfluramine (Fintepla®) is approved for the treatment of seizures associated with the rare epileptic encephalopathies Dravet syndrome and Lennox-Gastaut syndrome. Fenfluramine is extensively metabolized; thus, patients with hepatic impairment (HI) might experience changes in exposure to fenfluramine or its metabolites. In this phase 1 study, we investigated the pharmacokinetics (PK) and safety of a single oral dose of 0.35 mg/kg fenfluramine in subjects with mild (n = 8), moderate (n = 8), or severe (n = 7) HI (Child-Pugh A/B/C, respectively) and healthy control subjects (n = 22) matched for sex, age, and BMI. All subjects underwent serial sampling to determine total plasma concentrations of fenfluramine and its active metabolite, norfenfluramine. Hepatic impairment was associated with increases in fenfluramine exposures, mainly area-under-the-curve (AUC). Geometric least squares mean ratios (90% confidence intervals) for fenfluramine AUC0-∞ in mild, moderate, and severe HI versus healthy controls were 1.98 (1.36-2.90), 2.13 (1.43-3.17), and 2.77 (1.82-4.24), respectively. Changes in exposure to norfenfluramine in mild, moderate, and severe HI were minimal compared with normal hepatic function. Exposures to fenfluramine and norfenfluramine in all HI groups were within the ranges that have been characterized in the overall development program, including ranges examined in exposure-response relationships for efficacy and safety in patients, and determined to have an acceptable safety profile. Mild and moderate HI had a modest effect on fenfluramine exposure that was not clinically meaningful, whereas the higher fenfluramine exposure in severe HI may require dose reduction based on general caution in this population. The modest decrease in norfenfluramine exposure is not considered clinically relevant.

Pharmacokinetics and Safety of Firsocostat, an Acetyl-Coenzyme A Carboxylase Inhibitor, in Participants with Mild, Moderate, and Severe Hepatic Impairment.

Firsocostat is an oral, liver-targeted inhibitor of acetyl-coenzyme A carboxylase in development for the treatment of metabolic dysfunction-associated steatohepatitis. Hepatic organic anion transporting polypeptides play a significant role in the disposition of firsocostat with minimal contributions from uridine diphospho-glucuronosyltransferase and cytochrome P450 3A enzymes. This phase 1 study evaluated the pharmacokinetics and safety of firsocostat in participants with mild, moderate, or severe hepatic impairment. Participants with stable mild, moderate, or severe hepatic impairment (Child-Pugh A, B, or C, respectively [n = 10 per cohort]) and healthy matched controls with normal hepatic function (n = 10 per cohort) received a single oral dose of firsocostat (20 mg for mild and moderate hepatic impairment; 5 mg for severe hepatic impairment) with intensive pharmacokinetic sampling over 96 h. Safety was monitored throughout the study. Firsocostat plasma exposure (AUCinf) was 83%, 8.7-fold, and 30-fold higher in participants with mild, moderate, and severe hepatic impairment, respectively, relative to matched controls. Firsocostat was generally well tolerated, and all reported adverse events were mild in nature. Dose adjustment is not necessary for the administration of firsocostat in patients with mild hepatic impairment. However, based on the observed increases in firsocostat exposure, dose adjustment should be considered for patients with moderate or severe hepatic impairment, and additional safety and efficacy data from future clinical trials will further inform dose adjustment.

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis.

Acute liver failure (ALF) has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis. The silent information regulator sirtuin 1 (SIRT1)-mediated deacetylation affects multiple biological processes, including cellular senescence, apoptosis, sugar and lipid metabolism, oxidative stress, and inflammation. To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms. This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) testing. C57BL/6 mice were also intraperitoneally pretreated with SIRT1, p53, or glutathione peroxidase 4 (GPX4) inducers and inhibitors and injected with lipopolysaccharide (LPS)/D-galactosamine (D-GalN) to induce ALF. Gasdermin D (GSDMD)-/- mice were used as an experimental group. Histological changes in liver tissue were monitored by hematoxylin and eosin staining. ALT, AST, glutathione, reactive oxygen species, and iron levels were measured using commercial kits. Ferroptosis- and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction. SIRT1, p53, and GSDMD were assessed by immunofluorescence analysis. Serum AST and ALT levels were elevated in patients with ALF. SIRT1, solute carrier family 7a member 11 (SLC7A11), and GPX4 protein expression was decreased and acetylated p5, p53, GSDMD, and acyl-CoA synthetase long-chain family member 4 (ACSL4) protein levels were elevated in human ALF liver tissue. In the p53 and ferroptosis inhibitor-treated and GSDMD-/- groups, serum interleukin (IL)-1β, tumour necrosis factor alpha, IL-6, IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated. In mice with GSDMD knockout, p53 was reduced, GPX4 was increased, and ferroptotic events (depletion of SLC7A11, elevation of ACSL4, and iron accumulation) were detected. In vitro, knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels, the cytostatic rate, and GSDMD expression, restoring SLC7A11 depletion. Moreover, SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group, accompanied by reduced p53, GSDMD, and ACSL4, and increased SLC7A11 and GPX4. Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalN-induced in vitro and in vivo models. SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

Outcomes of Dorsolumbar and Lumbar Spinal Tuberculosis Treated by MinimallyInvasive and Open Techniques: A Prospective Comparative Study.

To compare the outcomes of minimally invasive and open techniques in the surgical management of dorsolumbar and lumbar spinal tuberculosis (STB). Skeletally mature patients with active STB involving thoracolumbar and lumbar region confirmed by radiology (X-ray, MRI) and histopathological examination were included. Healed and mechanically stable STB, patients having severe hepatic and renal impairment, coexisting spinal conditions such as ankylosing spondylitis and rheumatoid arthritis, and patients unwilling to participate were excluded from the study. The patients were divided in to two groups, group A consisted of patients treated by MIS techniques and group B consisted of patients treated by open techniques. All the patients had a minimum follow-up of 24months. A total of 42 patients were included in the study. MIS techniques were used in 18 patients and open techniques were used in 24 patients. On comparison between the two groups, blood loss (234ml vs 742ml), and immediate post-operative VAS score (5.26 vs 7.08) were significantly better in group A, whereas kyphotic correction (16° vs 33.25°) was significantly better in group B. Rest of the parameters such as duration of surgery, VAS score, ODI score and number of instrumented levels did not show significant difference between the two groups. MIS stabilization when compared to open techniques is associated with significant improvement in immediate post-operative VAS scores. The MIS approaches at 2-year follow-up have functional results similar to open techniques. MIS is inferior to open techniques in kyphosis correction and may be associated with complications.

Evaluating maternal toxicity induced by aqueous extract of Bambusa vulgaris shoot through biochemical, hematological, and histopathological assessment in pregnant Wistar rats

Exposure to teratogenic agents during pregnancy can lead to fetal abnormalities. Establishing histological, hematological, and biochemical parameters is pivotal to enhancing the evaluation of the effect of any substance on embryo-fetal development. The present study investigated the maternal toxicity of aqueous extract of Bambusa vulgaris Schrad. ex J.C. Wendl shoots in pregnant Wistar rats. The pregnant rats were then allocated into four groups (n=6): a control group (without treatment) and three test groups (treated with the extract 250, 500, and 1000 mg/Kg, respectively). The treatment was initiated on gestational day (GD) 6 and continued until the 15th day. On GD 20, all the rats were anesthetized and subjected to laparotomy. Blood samples were collected from the pregnant rats for hematological and biochemical analyses, while various organs were isolated for histopathological studies. The study demonstrates dose-dependent toxicity of the extract, with significant variations (P<0.001) observed in ALP and AST levels at the 1000 mg/kg dose, suggesting hepatic impairment in maternal subjects. Moreover, significant variations in total leukocyte and lymphocyte counts suggested pronounced inflammation or multi-organ dysfunction at this dose. Histopathological examination also revealed various indicators of multi-organ failure, including transmural mixed inflammation in the gall bladder, disruption of cardiac myofibre arrangement, tubular cell damage in the kidneys, cellular alterations in the liver, shrinking of pancreatic Langerhans islets, and lymphoid depletion in the spleen at 1000 mg/kg dose. These findings underscore the potential maternal toxicity associated with Bambusa vulgaris shoots, highlighting its potential risk for consumption during pregnancy and emphasizing the need for further research and caution regarding its use during this critical period.

Pueraria lobata Resistant Starch Regulating Lipid Metabolism and Gut Microbiota in High‐Fat Diet Mice

AbstractPueraria lobata resistant starch (PLRS) is prepared by modifying Pueraria lobata starch with pullulanase, and the PLRS modulate lipid metabolism disorders and gut microbiota structure are hypothesized in high‐fat diet (HFD) mice. The results reveal that the PLRS can alleviate lipid metabolism disorders by significantly upregulating the abundance of Akkermansia, Lactobacillus, Blautia, and Dubosiella, but markedly downregulating Staphylococcus in HFD mice. The PLRS may decrease the gain of weight, biochemical index, ameliorate hepatic impairment, and histopathological. Molecular mechanisms have elucidated that the PLRS may exert reducing fat accumulation and stabilize the gut microbiota effects through the modulation of the fatty acid metabolic signaling pathway and the PPAR signaling pathway. Therefore, these results suggest that this prebiotic carbohydrate may regulate lipid metabolism and gut microbiota in HFD mice and can be used to prepare healthy lipid‐lowering functional foods to attenuate obesity problems.