High Effective Therapy Research Articles

Uji Efek Nefroprotektif Ekstrak Etanol Daun Kari (Murraya Koenigii (L.) Spreng) Terhadap Kadar Blood Urea Nitrogen (BUN) Dan Kreatinin Tikus Putih Jantan Galur Wistar (Rattus Norvegicus) Yang Diinduksi Doksorubisin

Cancer is one of the leading causes of death in the world. A highly-effective therapy in cancer is chemotherapy using doxorubicin. Sustainable doxorubicin usage could damage the kidneys due to Reactive Oxygen Species (ROS) formation that could be seen by increased levels of BUN and creatinine. Curry leaves are commonly found in Aceh and has high antioxidant rate so it has the potential to suppress kidney damage due to the use of doxorubicin. These antioxidants could be useful for decreasing levels of BUN and creatinine. The purpose of this research is to test the nephroprotective effect of Ethanol Extract of Curry Leaves (EECL) to prevent kidney failure on doxorubicin induced wistar strain male white rats. The method of this research is experimental with post test only control group design. The number of samples used was 25 rats which were divided into 5 groups. Positive control group (given vitamin E), negative control group (given CMC-Na 0,5%), and treatment groups (given EECL at doses 50 mg/kgBB, 100 mg/kgBB, and 200 mg/kgBB) orally for 7 days straight and doxorubicin 15 mg/kgBB was induced on the 8th day. The results show that the BUN levels in the treatment group given EECL at doses 50 mg/ kgBB and 100 mg/kgBB are close to the positive control group, but the creatinine levels are still significantly different. Meanwhile, the treatment group that was given EECL at dose 200 mg/kgBB, both BUN and creatinine levels, are close to the positive control group. The conclusion of this study is that EECL has a nephroprotective effect on doxorubicin induced rats and the most effective dose is 200 mg/kgBB.

Vasoprotective effect of effective lipid-lowering therapy in patients with ST-segment elevation myocardial infarction

To study the vasoprotective effects of atorvastatin depending on the achievement of the target level of low-density lipoprotein cholesterol (LDL-C) in patients with ST-segment elevation myocardial infarction (STEMI) within 48 weeks of follow-up. Included were 112 STEMI patients who received atorvastatin 20-40-80 mg. On days 7-9 from the onset of the disease, after 24 and 48 weeks, ultrasound examination of the carotid arteries with RF technology and applanation tonometry were performed, the lipid profile was determined. The patients were divided into groups: group 1 (n=41) of highly effective therapy (HET) - who achieved the target LDL-C after 24 and 48 weeks; group 2 (n=29) in relatively effective therapy (RET) - achieving target values at 24th or 48th week; group 3 (n=42) insufficiently effective therapy (IET) - did not reach the target LDL-C. When examining the carotid arteries in the HET group, the intima-media thickness (IMT) decreased by 10.7-13.1%, the b index - by 14.9-26.3% after 24-48 weeks. In the RET group, the IMT regression was 10.4-13.3%; b index - 23.9% by the 48th week. In the IET group, the b index decreased by the 48th week by 14.3%. According to applanation tonometry in the HET group, the central pressure did not change. In the RET group, systolic pressure in the aorta increased by 10-15.7% after 24-48 weeks, pulse pressure - by 33.9% by the end of observation. With IET, the increase was 8.6-6.8 and 19.8-25.9%, respectively. The odds ratio of developing endpoints in the RET group was 4.7 (95% CI 1.2-26.4; p=0.02), in the IET group - 3.9 (95% CI 1.1-24.8; p=0.03) compared with HET. The most pronounced vasoprotective effect and a decrease in cardiovascular risk are associated with the achievement of the target LDL-C throughout the entire treatment period.

Comparative discontinuation, effectiveness, and switching practices of dimethyl fumarate and fingolimod at 36-month follow-up

BackgroundDimethyl fumarate (DMF) and fingolimod (FTY) are approved oral disease modifying therapies (DMTs) for relapsing multiple sclerosis (MS). There are currently no known head-to-head studies comparing DMF and FTY over 36 months, which leaves their relative effectiveness unknown. ObjectiveTo assess real-world discontinuation, effectiveness, and switching practices of DMF and FTY over 36 months along with disease activity after switching DMT. MethodsPatients prescribed DMF (n = 737) and FTY (n = 535) from two academic MS centers were retrospectively reviewed. Discontinuation and effectiveness outcomes were assessed using propensity score (PS) weighting. PS model covariates included sociodemographics and clinical and MRI characteristics. ResultsDiscontinuation was more common in DMF (58.3%) versus FTY (45.2%) over 36 months [OR = 1.81, 95% CI (1.41–2.31), p < .001], largely driven by intolerance [OR = 1.63, 95% CI (1.18–1.73), p < .001]. There were no differences in clinical relapses [OR = 1.27, 95% CI (0.90–1.79), p = .17], gadolinium-enhancing (GdE) lesions [OR = 1.25, 95% CI (0.85–1.84), p = .26], or new T2-hyperintense lesions [OR = 0.99, 95% CI (0.74–1.32), p = .93]. Within 12 months of DMF/FTY discontinuation, switchers to highly effective therapy (HET) versus other DMTs (injectables/orals) had fewer relapses (DMF/HET, 5.9% versus DMF/Other, 14.2%, p = .03; FTY/HET, 11.6% versus FTY/Other, 18.0%, p = .04) and fewer GdE lesions post-FTY (DMF/HET, 10.3% versus DMF/Other, 14.3%, p = .36; FTY/HET, 11.9% versus FTY/Other, 21.5%, p = .04). ConclusionThis combined analysis showed similar effectiveness for DMF and FTY over 36 months with higher DMF discontinuations. Disease activity was lower in switchers to HET versus injectable/oral therapies after DMF/FTY cessation.

PWE-094 Understanding The Efficacy of Faecal Microbiota Transplantation in Clostridium Difficile Infection: Re-Establishment of Gut Microbiota with The Ability to Degrade Bile?

Introduction Faecal microbiota transplantation (FMT) has recently emerged as a highly-effective therapy for recurrent/ refractory Clostridium difficile (recently re-named Peptoclostridium difficile) infection (CDI); however, the specific mechanisms underlying the efficacy of FMT remain largely unclear. Given that different bile salt metabolites differentially affect C. difficile ’s ability to germinate and grow both in vitro and in vivo, we hypothesised that CDI is characterised by perturbed bile acid metabolism, and that FMT may exert its efficacy through re-establishment of gut microbiota that restore this process to normal. Methods Stool samples were collected from healthy volunteer donors participating in an FMT programme, whilst serial stool samples were collected from a patient successfully treated with FMT for refractory CDI both pre- and post-transplantation. Samples were assayed for structure of the gut microbiota using 16 S rRNA gene sequencing, and for bile acid profiling via liquid chromatography mass spectrometry (LC-MS). Presence of bile salt hydrolases (responsible for deconjugation of glycine- and taurine-conjugated primary bile acids within the gut) was assessed via PCR of bacterial DNA extracted from stool. Results A 61 year-old man with refractory CDI was treated with FMT. He demonstrated a modest improvement in diarrhoea after a first FMT, but an immediate, complete and sustained resolution of symptoms after a second FMT from a different donor (performed two weeks after the first). 16 S rRNA gene sequencing demonstrated a pattern of faecal bacterial communities that closely resembled that of the healthy donors by one week after the second FMT. Faecal LC-MS analysis revealed the patient’s gut bile acid profile pre-FMT to be enriched sixfold in taurocholic acid (a potent trigger for C. difficile spore germination in vitro ). Post-FMT, the patient’s gut bile acid profile resembled that of healthy donors, with loss of taurocholate and enrichment of secondary bile acids (which are recognised in vitro as inhibitors of C. difficile growth). PCR of bacterial DNA extracted from faeces displayed no detectable BSH genes in the recipient either pre-FMT or by one week following the first FMT, but BSH presence was confirmed in the recipient by one week following the second FMT, as well as in both donors. Conclusion FMT may restore bile-degrading members of the gut microbiota, and consequently restore a normal bile acid metabolism to the gut that protects against C. difficile germination. Disclosure of Interest None Declared