Tinospora Cordifolia: A Literature Review on Therapeutic uses and Pharmacological Actions

Tinospora cordifolia is a medicinal ayurvedic herb having vast benefit to human health. It is come under the climbing shrub, which belongs to family Menispermaceae and is inherent to India and some extent to China also, and some parts of Australia and Africa. Other names used for Tinospora cordifolia are Guduchi or Amrita or Giloy. Not a single part but whole plant has its own pharmacological effect for human well-being. Tinospora cordifolia has chemical constituents like terpenoids, alkaloids, steroids, lignans, flavonoids and glycosides. It has many pharmacological activities such as immunomodulation, anti-diabatic, antifungal, in hepatotoxicity (hepatic disorder), anti- cancer, anti-HIV potential, antitoxic effect, and in Parkinson disease. This review paper will discuss about the various properties/activities of the plant.

Evaluation of Platelet Counts in the Normal Pregnancy and other Gestational Conditions at Tertiary Care Hospital of Sindh

Background: During gestational period, the most common disorder is hypertension that directly affects the gestation. The frequency of gestational hypertension is increasing day by day and ultimately the pressure is developed on the endothelial wall. Gestational hypertension mostly reduces the platelet counts. Aim of Study: The major theme of this research is evaluating the count of platelet during pregnancy and other gestational conditions. Methodology: A Retrospective research was carried out for the period of 06 months at Gynae and Obstetrics ward at tertiary care hospital of Sindh, Pakistan. Total 104 females were selected with different gestational age and trimester. A questionnaire was filled by all participants that were comprised of demographic data and gestational conditions such as preeclampsia, eclampsia, parity and seizure episodes. Females with highest risk factors diseases such as Diabetes, Hepatic disorder, Anemia, renal disorder and cardio vascular disease were not included in our research. Blood samples were collected from all selected participants for proper platelet count and data was compared with normal ranges of platelet count among the pregnant females. Data was analyzed by using statistical software 24.00 versions. Results: It was observed that 49 patients were having normal pregnancy, 32 had preeclampsia and 23 had eclampsia. 38 participants were first timer & 52 were having second time parity. 58 participants had 2nd trimester of pregnancy. According to condition of anemia, 27 had severe anemic condition whereas 43 had moderate anemic condition. 49 participants had reduced level of platelet count and 17 had very low platelet count. Severity of gestation can be managed through proper management and physician instructions. Hypertension was measured through severity scale, 29 patients had moderate level of hypertension and 22 had severe level of hypertension. 19 participants had very abnormal level of blood count. Conclusion: It was concluded that proper diagnostic test should be conducted on time for proper management of reduced platelet count and there should be proper mass counseling should be conducted in order to overcome the deficiency of platelet count. There should be proper diet and exercise during pregnancy that can manage the condition of hypertension. Severity of gestation can be managed through proper management and physician instructions.

Disseminated Alveolar Echinococcosis.

Alveolar echinococcosis (AE) is caused by the larval form of the tapeworm Echinococcus multilocularis. In humans, E. alveolaris metacestode cells proliferate in the liver inducing a hepatic disorder that mimics liver cancer and can spread to other organs. From 1960 to 1972 mortality was at 70% and 94% after 5 and 10 years of follow-up, respectively. Since then, studies have shown an increasing trend towards improving survival rates [1]. As AE is also spreading to new areas of Eastern Europe, researchers seek to better understand the clinical presentation of pathology, including asymptomatic forms. Clinical case; One 36-year-old woman from Peshkopia has been admitted to the Gastrohephatology department on 20.07.2011 with fatigue, anorexia, dull pain in right hypochondrium, mild epigastric pain, bloating, and weight loss. The epidemiological anamnesis showed that the patient lived in the village and had pets. On physical examination, the patient appeared severely ill with jaundice, massive hepatomegaly, massive mass in the mesogastric area, and anxiety. Laboratory examinations were as follows: Hb 11.1 g/dl, sediment 25 mm/h; leukocytes 6700/mm3; platelets 127000/mm3; prothrombin level 60%, uremia 12.7 mmol/l; creatinine 0.78 mmol /l; ALP 127 U/I; AST 15 U/I; ALT 37 U/I; GGT 131 U/I; bilirubin 3.7 mg/l, albumin 2.8 gr / l, total protein 8.1 gr / l, HbsAg negative, anti-HCV negative. Regarding serology, the titer of anti-echinococcal antibodies was positive (22, n = 11) Conclusions: Clinical presentation and radiologic imaging findings of disseminated alveolar echinococcosis can mimic metastatic malignancy, and diagnosis can be challenging in atypically advanced cases. As the incidence of human alveolar echinococcosis appears to be increasing and, physicians should be aware of alveolar echinococcosis, its epidemiology, and its clinical features.

Stem cell therapies for autoimmune hepatitis

Autoimmune hepatitis is a chronic inflammatory hepatic disorder which may cause liver fibrosis. Appropriate treatment of autoimmune hepatitis is therefore important. Adult stem cells have been investigated as therapies for a variety of disorders in latest years. Hematopoietic stem cells (HSCs) were the first known adult stem cells (ASCs) and can give rise to all of the cell types in the blood and immune system. Originally, HSC transplantation was served as a therapy for hematological malignancies, but more recently researchers have found the treatment to have positive effects in autoimmune diseases such as multiple sclerosis. Mesenchymal stem cells (MSCs) are ASCs which can be extracted from different tissues, such as bone marrow, adipose tissue, umbilical cord, and dental pulp. MSCs interact with several immune response pathways either by direct cell-to-cell interactions or by the secretion of soluble factors. These characteristics make MSCs potentially valuable as a therapy for autoimmune diseases. Both ASC and ASC-derived exosomes have been investigated as a therapy for autoimmune hepatitis. This review aims to summarize studies focused on the effects of ASCs and their products on autoimmune hepatitis.

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice

Background: Atezolizumab plus bevacizumab was approved for patients with hepatocellular carcinoma (HCC). Although clinical trials have revealed its efficacy, the outcomes in the real-world clinical practice are unclear. We retrospectively evaluated the efficacy and safety of atezolizumab plus bevacizumab for HCC. Materials and Methods: This is a multicenter study conducted between November 2020 and March 2021. Among the 61 patients, 51 were assessed for progression-free survival (PFS), therapeutic response, and adverse events (AEs). Results: The median PFS was 5.4 months. The objective response rate (ORR) was 35.3%. The disease control rate (DCR) was 86.3%. The incidence rates of AEs at any grade and grade >3 were 98.0% and 29.4%, respectively. The most frequent AE at any grade and grade >3 was hepatic disorder. In patients with a previous history of molecular targeted agent (MTA) or the degree of albumin-bilirubin (ALBI) grade, there were no significant differences in the PFS, ORR, DCR, and incidence rates of AEs. Conclusion: The study demonstrated that atezolizumab plus bevacizumab was effective and safe for patients with HCC even in the real-world setting including patients with a previous MTA history or other than ALBI grade 1.

Kandungan Bilangan Peroksida Minyak Goreng Pedagang di Jalan Perintis Kemerdekaan Kota Padang

Background. Indonesian usually using repeatedly cooking oil for deep frying process. The repeated use of cooking oil can be found among street vendors. Consumption of repeatedly cooking oil could lead to hepatic disorder, cardiovasular disorder and even cancer. Objective. The research aims to describe and analyze peroxide value in cooking oil used by street vendors in Perintis Kemerdekaan street in Padang City. Methods. This is a descriptive research. The reseacrh objects were taken by purposive sample method and 23 samples cooking oil used by traders. This research was conducted at Clinical Laboratory of West Sumatera from October 2019 to May 2020. Results. This research found out 14 from 23 of cooking oil used by street vendors have peroxide value above the Indonesian National Standard (abbreviated SNI) 01-3741-2013. Cooking oil used by fritter street vendors have average peroxide value is 15.10 mEq O2/kg while pecel catfish and chicken street vendors is 10.29 mEq O2/kg. The avarage peroxide value in each type of cooking oil are bulk 10,81 mEq O2/kg, branded 14,64 mEq O2/kg and mixture 16,28 mEq O2/kg. Conclusion. More than half of the samples tested had exceed the maximum peroxide values (> 10 mEq O2/kg) and the highest average are found in fritter street vendor and mixture of bulk and branded cooking oil.

POS1035 UPADACITINIB AS MONOTHERAPY AND IN COMBINATION WITH NON-BIOLOGIC DMARDs FOR THE TREATMENT OF PSORIATIC ARTHRITIS: SUBGROUP ANALYSIS FROM TWO PHASE 3 TRIALS

Background:Approximately 40% of PsA patients (pts) on advanced therapy are on monotherapy.1,2 Upadacitinib (UPA) showed efficacy and safety in pts with active PsA in the Phase 3 SELECT-PsA 1 and SELECT-PsA 2 clinical trials.3,4Objectives:Assess efficacy and safety in subgroups of pts treated with UPA as monotherapy or in combination with non-biologic disease-modifying antirheumatic drugs (non-bDMARDs).Methods:The SELECT-PsA program enrolled pts with prior inadequate response (IR) or intolerance to ≥1 non-bDMARD (N=1705) and prior IR or intolerance to ≥1 bDMARD (N=642). Data from both trials was integrated for pts receiving placebo (PBO), UPA 15 mg once daily (QD) and UPA 30 mg QD. Stable background treatment of ≤2 non-bDMARDs was permitted, but not required. Analysis includes UPA monotherapy vs combination therapy for endpoints: ACR20/50/70 responses and change from baseline in pain and HAQ-DI (Wk 12); Static Investigator Global Assessment of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline and PASI75/90/100 responses (Wk 16); proportion of pts achieving resolution of enthesitis, dactylitis, and minimal disease activity (Wk 24). Binary outcomes, using the Cochran-Mantel-Haenszel-method and continuous outcomes, using mixed-effects model, were analyzed for repeated measures in the subgroups of UPA monotherapy and combination therapy. Point estimates and 95% confidence intervals (CIs) of PBO subtracted treatment effect were calculated. Treatment-emergent adverse events (TEAEs) were analyzed.Results:Of 1916 pts, 574 (30%) received monotherapy and 1342 (70%) received combination therapy; 84% in combination therapy group received MTX +/- another non-bDMARD. Both UPA monotherapy and combination therapy led to improvements in efficacy vs PBO and across endpoints, for each dose, generally consistent point estimates of PBO subtracted treatment effect and associated overlapping CIs were observed (Figure 1). Generally, frequency of AEs and serious AEs, were comparable with UPA administered as monotherapy and combination therapy (Table 1). Frequency of AEs of serious infections and hepatic disorder were lower with monotherapy while frequency of AEs leading to discontinuation of study drug were lower with combination therapy. Most hepatic disorders were transient transaminase elevations.Conclusion:In the SELECT PsA trials, efficacy and safety of UPA was generally consistent when administered as monotherapy or when given in combination with non-bDMARDs. Results from this analysis support the use of UPA with or without concomitant non-bDMARDs.References:[1]Ianculescu I and Weisman MH, Clin Exp Rheumatol 2015; 33:S94–S97.[2]Mease PJ, et al. RMD Open 2015; 1:e0000181.[3]McInnes IB, et al. Ann Rheum Dis, 2020; 79:12.[4]Genovese MC, et al. Ann Rheum Dis, 2020; 79:139.Acknowledgements:AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea of AbbVie Inc.Disclosure of Interests:Peter Nash Speakers bureau: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Consultant of: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Grant/research support from: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Pascal Richette Speakers bureau: AbbVie, Biogen, Janssen, BMS, Roche, Pfizer, Amgen, Sanofi-Aventis, UCB, Lilly, Novartis, and Celgene, Consultant of: AbbVie, Biogen, Janssen, BMS, Roche, Pfizer, Amgen, Sanofi-Aventis, UCB, Lilly, Novartis, and Celgene, Laure Gossec Speakers bureau: Abbvie, Amgen, Biogen, BMS, Celgene, Lilly, Novartis, Pfizer, Janssen, Sandoz, Sanofi-Aventis, UCB, Consultant of: Abbvie, Amgen, Biogen, BMS, Celgene, Lilly, Novartis, Pfizer, Janssen, Sandoz, Sanofi-Aventis, UCB, Grant/research support from: Abbvie, Amgen, Biogen, BMS, Celgene, Lilly, Novartis, Pfizer, Janssen, Sandoz, Sanofi-Aventis, UCB, Antonio Marchesoni Speakers bureau: AbbVie, BMS, Celgene, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Celgene, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Novartis, UCB, Grant/research support from: UCB, Koji Kato Shareholder of: AbbVie, Employee of: AbbVie, Erin McDearmon-Blondell Shareholder of: AbbVie, Employee of: AbbVie, Elizabeth Lesser Shareholder of: AbbVie, Employee of: AbbVie, Reva McCaskill Shareholder of: AbbVie, Employee of: AbbVie, Dai Feng Shareholder of: AbbVie, Employee of: AbbVie, Jaclyn Anderson Shareholder of: AbbVie, Employee of: AbbVie, Eric Ruderman Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, and Pfizer.

Metronidazole enhances steatosis-related early-stage hepatocarcinogenesis in high fat diet-fed rats through DNA double-strand breaks and modulation of autophagy

Nonalcoholic fatty liver disease is a hepatic disorder with deposition of fat droplets, and has a high risk of progression to steatosis-related hepatitis and irreversible hepatic cancer. Metronidazole (MNZ) is an antiprotozoal and antimicrobial agent widely used to treat patients infected with anaerobic bacteria and intestinal parasites; however, MNZ has also been shown to induce liver tumors in rodents. To investigate the effects of MNZ on steatosis-related early-stage hepatocarcinogenesis, male rats treated with N-nitrosodiethylamine following 2/3 hepatectomy at week 3 were received a control basal diet, high fat diet (HFD), or HFD containing 0.5% MNZ. The HFD induced obesity and steatosis in liver, accompanied by altered expression of Pparg and Fasn, genes related to lipid metabolism. MNZ increased nuclear translocation of lipid metabolism-related transcription factor peroxisome proliferator-activated receptor gamma in hepatocytes, together with altered liver expression of lipid metabolism genes (Srebf1, Srebf2, Pnpla2). Furthermore, MNZ significantly increased the number of preneoplastic liver foci, accompanied by DNA double-strand breaks and late-stage autophagy inhibition, as reflected by increased levels of γ-H2AX, LC3, and p62. Therefore, MNZ could induce steatosis-related hepatocarcinogenesis by inducing DNA double-strand breaks and modulating autophagy in HFD-fed rats.