A case report on anti-tubercular agent induced hepatotoxicity

Hepatotoxicity is the serious adverse effect of tuberculosis treatment and it leads to the discontinuation of Anti-tubercular agent (ATT) causing increased drug resistance, morbidity and mortality. We report a 69 years old male patient with ATT induced hepatotoxicity.

Relationship between body mass index, liver enzymes and high-sensitivity C-reactive protein in type 2 diabetes mellitus patients

Background: Obesity is a frequent co-morbid condition associated with excessive increase in weight. It is one of the most important modifiable risk factors in the pathogenesis of type 2 diabetes mellitus (T2DM). Obesity may be associated with liver disease and the progression of hepatic dysfunction. Also, highly sensitive C-reactive protein (hsCRP), which is elevated in inflammatory situations, can be produced by monocyte-derived macrophages in adipose tissue may also disrupt liver functions. Methods: A case control study with 50 patients of T2DM and 50 age and sex matched individuals were taken to serve as controls. Results: The body mass index (BMI) and waist circumference were increased in T2DM patients as compared to controls. However, the variations in liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum alkaline phosphatase (ALP) and hsCRP were increased in individuals of normal BMI as compared with individuals of overweight BMI. Conclusions: Individuals with normal Body mass index had an increased risk of developing T2DM along with progression of hepatic dysfunction. No associations were observed between chronic low-grade inflammation and BMI and with pathogenesis of obesity-related insulin resistance.

The effects of antibiotics on liver enzymes in pregnancy

Background: Antibiotics are increasingly being prescribed during pregnancy. Even though safe non-teratogenic drugs are prescribed, due to altered pharmacokinetics during pregnancy can have adverse effects on hepatic metabolism. Methods: This was a prospective analytical study conducted in the department of obstetrics and gynecology at ESIC Medical College and PGIMSR, Bengaluru, Bengaluru from August 2022 to January 2023, 62 pregnant women diagnosed with infection were admitted and evaluated for the effects of antibiotics on liver enzymes. All cases had undergone a baseline Liver function test before antibiotic therapy were compared and statistically analyzed with the liver enzymes, alanine transaminase (ALT), and aspartate transaminase (AST) values after 7 days of the antibiotic course. Results: In this study, the mean age of pregnant women enrolled was 26±3.62 years. Both primi (45.2%) and multigravida (54.8%) were equally represented. The most commonly prescribed antibiotic was cefotaxime (67.7%). The mean pre AST was 17.92±11.28 and post-AST was 18.34±15.55 U/l (paired t-test =0.861) and the mean pre-ALT was 13.09±19.82 and post-AST was 11.7±8.01 U/l (paired t-test =0.533). Hence there were no significant changes in post-AST and post-ALT compared to Pre AST and ALT values. Conclusions: In this study the common antibiotics administered were cephalosporins and they didn’t show any effects on AST or ALT values after completing the antibiotic course.

A Survey on Current Activities and Issues of Pharmacists at Facilities Calculating Fees for the Implementation of Antimicrobial Stewardship in Ehime / 社会薬学

Although the fees for the implementation of antimicrobial stewardship (AS addition) were newly established in the 2018 revision of medical fees, more detailed activities and issues of pharmacists at facilities calculating AS addition have not been clarified so far. Therefore, to understand the current status of AS activities and problems, we conducted a questionnaire survey of facilities that calculate the additional fee for infection prevention measures 1 and investigated whether there are differences in AS activities between facilities where pharmacists are full-time employees and facilities where non-pharmacists are full-time employees. The results showed that the number of antimicrobial agents used by full-time pharmacists was larger than that by non-pharmacists. In addition, the frequency of AS was lower for non-full-time workers than for full-time workers, with most full-time workers performing AS every day, while non-full-time workers performing AS two to three days a week. In addition, non-full-time workers lacked human resources and work time, and did not have sufficient work materials. The survey revealed that AS activities’ current status and problems differ between full-time and non-full-time employees.

Astragalin Inhibits Apoptosis of Cerebral Cortex Neurons in APP/PS1 Mice / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of Astragalin （AST） on apoptosis of cerebral cortex neurons in APP/PS1 transgenic mice. MethodsEighteen six-month-old male APP/PS1 transgenic mice were randomly divided into APP/PS1 group， APP/PS1+ 40 mg/kg AST group and APP/PS1+ 20 mg/kg Donepezil （DNP） group， with six mice in each group. At the same time， six male C57BL/6 mice were selected as the normal control group. After intraperitoneal injection of AST once a day and continuous administration for one month， we used Tunel staining to detect the apoptosis of neurons in the cerebral cortex of APP/PS1 mice； immunofluorescent staining to examine the expression of apoptosis-related proteins Bax， Bcl-2， Caspase9 and Cleaved-Caspase3 in the cerebral cortex neurons of APP/PS1 mice； Western blot method to evaluate the changes of the expression of Bax， Bcl-2， Caspase9 and Caspase3. ResultsTunel staining showed that 40 mg/kg AST and 20 mg/kg DNP both reduced the apoptosis of neurons in the cerebral cortex of APP/PS1 mice， AST with more significant inhibition effect. Immunofluorescent staining revealed that 40 mg/kg AST and 20 mg/kg DNP both inhibited the expression of Bax， Caspase9， and Cleaved-Caspase3， and icreased the expression of Bcl-2 in the cerebral cortex neurons of APP/PS1 mice. Western blot results further confirmed that 40 mg/kg AST and 20 mg/kg DNP both down-regulated the expression of Bax （P < 0.05， P < 0.05）， Caspase9 （P < 0.005， P < 0.05） and Caspase3 （P < 0.0001， P < 0.0001） ， and up-regulated the expresstion of Bcl-2 （P < 0.05， P < 0.05） in the cerebral cortex neurons of APP/PS1 mice. ConclusionsAST can inhibit the apoptosis of cerebral cortex neurons in APP/PS1 mice.

Prevalence of Hepatitis D Virus among People Attending the Antiretroviral Clinic and the Effect on the Liver Function Enzymes

Hepatitis D virus is an incomplete RNA virus requiring the assistance of the hepatitis B virus, specifically the HBsAg, to be infectious in humans. This study was designed to determine the prevalence of HDV among HIV patients and the effect on liver enzymes. The study was conducted at the Rivers state University Teaching hospital, Port Harcourt, Rivers State. Blood samples were obtained through vein puncture from 93 adults of which 41(44%) were males while 52(56%) were females between the ages 18 and 70 years attending the antiretroviral clinic and CD4+ cell count was also obtained. The samples were preserved at -20ºC. Each of the samples was tested using a SWE-Care rapid strip (China) for the presence of HBsAg. HDV antibody was detected using a Dia. Pro ELISA kit (Italy). The AST, ALT and ALP were determined. SPSS 21 was used to analyze the data and P values were determined. From the total samples collected, 7(7.5%) of them were positive to the HBsAg test of which 3(3.2%) were males, while 4(4.3%) of them were females. Of the 7 people positive to the HBsAg, 6(6.4%) were positive to the HDV antibody with 3(3.2%) females and 3(3.2%) males. There was significant depletion of the CD4+ cells across the groups. For the liver function test, the P values were ? 0.05 for AST, ALT and ? 0.05 for ALP. The HDV infection from the study was not gender, nor age based and suggests a negative impact on the CD4 cells. The liver function enzyme analysis, suggest higher risk of hypertension in HIV/HBV/HDV infection.

Evaluation of Pathogens Causing Urinary Tract Infection and Their Sensitivity Pattern

Background: UTI constitute a major public health problem in India accounting 2nd most common infection next to respiratory tract infection. They are responsible for increasing treatment cost and significant morbidity.Aim:-To determine the incidence of UTI, evaluation of pathogens responsible and their antimicrobial susceptibility pattern in the population.Methods:Urine samples were collected from 300 patients attending the OPD Patna medical college, Patna during the period of 18 months (January 2017 to June 2018) Antimicrobial sensitivity testing was done for the bacterial isolates present in the sample by Kirby- Bauer disc diffusion method. Only those samples were taken into consideration which develops count equal to or greater than 1*105CFU/ml as indicated by Kass.Results:Out of 300 samples collected 146 (48.66%)) yielded bacterial growth. Out of 146 culture isolates E.Coli was the most common pathogen followed by klebsiella, CoNS and staphylococcus. Antibiotic sensitivity was performed on all the isolates. It was observed that highest sensitivity was 49.31% to amikacin, gentamycin (45.89%), nitrofurantoin (38.35%) meropenem (27.39%).Conclusions:It was observed that high grade of resistance to ampicillin, cotrimoxazole, ciprofloxacin, cefuroxime, chloramphenicol, cefotaxime, cefazolin, amoxicillin + clavulanic acid and gentamycin is present as a result of misuse or improper use of antibiotic in the community. Hence urine culture is necessary for the diagnostic screening of UTI before the treatment.

Prospective Evaluation of Raised Liver Transaminases in Asymptomatic Patients Attending OPD in a Tertiary Care Hospital

Background: Liver diseases are a cause of worldwide morbidity .The course is usually long and has no signs before the development of late stage disease. The only indicative markers are liver enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) during asymptomatic period. There is a paucity of data from our subcontinent regarding the prevalence, risk factors and etiology of asymptomatic chronically raised liver enzymes.The aim of the study was to determine the prevalence, risk factors and etiology associated with unexplained chronically raised liver transaminases in patients attending OPD in a tertiary care hospital.Methods:This was a prospective study conducted in the Department of Gastroenterology, MMIMSR, Mullana from July 2019-Dec 2020 in 50 patients who presented with chronically raised liver enzymes. Detailed comprehensive history, physical examination and investigation was done to identify etiology and risk factors associated with raised liver enzymes.Results:566 patients were screenedfor inclusion in the study. The prevalence of raised transaminases in asymptomatic patients was 9.4%. NAFLD was the most common etiology of raised liver transaminases, seen in 70 % of patients followed by Hepatitis C and Hepatitis B. Dyslipidemia was the most important risk factor associated with NAFLD.Conclusion:NAFLD should be kept in mind while dealing patients with unexplained transaminitis. Earlier detection could help halt the progression to chronic liver disease.

Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.

Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses

Constitutive androstane receptor induced-hepatomegaly and liver regeneration is partially

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67

Serum liver enzyme profile in Timor deer (Cervus timorensis) with fascioliasis in Indonesia

@#Timor deer (Cervus timorensis) at Surabaya zoo, Indonesia, that were found to be naturally infected with Fasciola, showed elevated level of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Of a total of 75 deer examined, 12 (25%) of the 47 adult deer and 8 (29%) of the 28 juvenile deer were found to be infected with fascioliasis, as evidenced by the shedding of the parasite eggs. The level of ALT, AST and ALP were significantly elevated (p<0.05) in all the infected deer. Only Fasciolainfected deer showed elevated serum liver enzyme. Deer with elevated enzyme level show a trend that positively correspond with higher Egg per gram of feces (EPG). The average size of the parasite eggs at 169.0±11.1 × 96.0±3.5μm, correspond well with that of Fasciola gigantica. No other trematode eggs were observed besides that of F. gigantica. There was no significant difference in the enzyme profile between the two sexes in both the infected and the uninfected group. This is the first report of the elevation of serum liver enzyme in Timor deer that is associated with not only fascioliasis and also correspond positively with the EPG.

Effect of tiopronin combined with glutathione on biochemical indicators of patients with non-alcoholic fatty liver / 药学实践杂志

Objective To observe the effect of tiopronin combined with glutathione on the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT),blood fat and laminin (LN) in patients with non-alcoholic fatty liver. Methods A total of 84 non-alcoholic fatty liver patients admitted to our hospital from March 2018 to September 2019 were selected and randomly divided into control group and observation group, with 42 cases in each group. The control group was treated with tiopronin, and the observation group was treated with glutathione and tiopronin. The levels of ALT, AST, GGT and blood fat were recorded and compared before and after treatment. Results After treatment, the levels of ALT, AST and GGT in the two groups were significantly lower than before treatment (P<0.05). After treatment, the levels of ALT, AST, and GGT in the observation group were different from those in the control group, which was statistically significant (P<0.05). Before treatment, there was no difference in serum TC, TG, and LDL levels between the two groups, which was not statistically significant (P>0.05). The above-mentioned serum levels of the observation group after treatment were lower than those in the control group, and there was a difference, which was statistically significant (P<0.05); the levels of PCⅢ, PCⅣ, and LN in the treatment group after treatment were significantly lower than those of the control group. The difference was statistically significant (P<0.05). Conclusion The application of tiopronin combined with glutathione in the treatment of non-alcoholic fatty liver can promote the recovery of liver function and reduce the concentrations of TC, TG and LDL, which is worthy of clinical promotion.

Synergetic delivery of triptolide and Ce6 with light-activatable liposomes for efficient hepatocellular carcinoma therapy

Hepatocellular carcinoma (HCC) has been known as the second common leading cancer worldwide, as it responds poorly to both chemotherapy and medication. Triptolide (TP), a diterpenoid triepoxide, is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC. However, its clinical application has been limited owing to its severe systemic toxicities, low solubility, and fast elimination in the body. Therefore, to overcome the above obstacles, photo-activatable liposomes (LP) integrated with both photosensitizer Ce6 and chemotherapeutic drug TP (TP/Ce6-LP) was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy. The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention (EPR) effect. Under laser irradiation, the photosensitizer Ce6 generated reactive oxygen species (ROS) and further oxidized the unsaturated phospholipids. In this way, the liposomes were destroyed to release TP. TP/Ce6-LP with NIR laser irradiation (TP/Ce6-LP+L) showed the best anti-tumor effect both

Hepatocellular Liver Function of Immunosuppressed Rats with Oral Candidiasis after Hyperbaric Oxygen Treatment: Alanine Transaminase and Aspartate Transaminase Levels

ABSTRACT@#Hepatocellular utility is observed by measuring the hepatocellular enzymes. Changes in its serum levels are related to liver dysfunction. Liver is one of the immunoprotective organs. Continuous use of immunosuppressive drugs can cause oral candidiasis and give effects to liver function. Hyperbaric oxygen treatment (HBOT), while reducing fungal infections, can also repair the liver function. The aim of this study was to investigate the alanine transaminase (ALT) and aspartate transaminase (AST) levels of immunosuppressed rats with oral candidiasis treated with hyperbaric oxygen. Twelve Wistar rats were divided into three groups: K− (normal/ healthy), K+ (oral candidiasis immunosuppressed rats), and P (oral candidiasis immunosuppressed rats treated hyperbaric oxygen). K+ and P groups were immunosuppressed by giving dexamethasone 0.5 mg/day/rat orally for 14 days, added with tetracycline 1 mg/day/rat. HBOT was given in five days successively. Blood serum of rats in all groups were taken to calculate the ALT and AST levels. ALT and AST levels in K+ showed higher value than K− and P groups. The data were analysed with one-way ANOVA test and showed significant difference in ALT levels (p < 0.05), while in AST levels there was no significant difference among the groups (p > 0.05). This study showed that HBOT affected the ALT and AST levels of immunosuppressed rats with oral candidiasis.

Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy

Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG

Proteomics and metabolic phenotyping define principal roles for the aryl hydrocarbon receptor in mouse liver

Dioxin-like molecules have been associated with endocrine disruption and liver disease. To better understand aryl hydrocarbon receptor (AHR) biology, metabolic phenotyping and liver proteomics were performed in mice following ligand-activation or whole-body genetic ablation of this receptor. Male wild type (WT) and

Bile acid homeostasis in female mice deficient in

Bile acids (BAs) are amphipathic molecules important for metabolism of cholesterol, absorption of lipids and lipid soluble vitamins, bile flow, and regulation of gut microbiome. There are over 30 different BA species known to exist in humans and mice, which are endogenous modulators of at least 6 different membrane or nuclear receptors. This diversity of ligands and receptors play important roles in health and disease; however, the full functions of each individual BA

3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C, Nanopore, and RNA sequencing

The three-dimensional (3D) conformation of chromatin is integral to the precise regulation of gene expression. The 3D genome and genomic variations in non-alcoholic fatty liver disease (NAFLD) are largely unknown, despite their key roles in cellular function and physiological processes. High-throughput chromosome conformation capture (Hi-C), Nanopore sequencing, and RNA-sequencing (RNA-seq) assays were performed on the liver of normal and NAFLD mice. A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments, topologically associated domains (TADs), and chromatin loops by Hi-C, and whole genome sequencing identifying structural variations (SVs) and copy number variations (CNVs) by Nanopore sequencing. We identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements, between normal and NAFLD mice, and revealed gene dysregulation frequently accompanied by these variations. Candidate target genes were identified in NAFLD, impacted by genetic rearrangements and spatial organization disruption. Our data provide a high-resolution 3D genome interaction resource for NAFLD investigations, revealed the relationship among genetic rearrangements, spatial organization disruption, and gene regulation, and identified candidate genes associated with these variations implicated in the pathogenesis of NAFLD. The newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.