danial dehghan
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It is believed that preformed antibodies are responsible for blood transfusion reactions and transplant rejections. In order to remove a tumor, the tissue must be rejected. On the basis of transfusion reaction and transplantation immunology, we hypothesized that allogeneic serum can inhibit tumor growth when injected intra-tumor. Initially, an in vitro cytotoxicity test was conducted using the C57BL/6 serum (intact or decomplemented) in combination with the BALB/c-originating CT26 cell line. The CT26 cell line was used to establish a mouse model of colon cancer. When the tumor was palpable, C57BL/6 serum was injected intra-tumor. In addition to tumor size, hypoxia, metastatic capacity, angiogenesis, and metabolic and inflammatory status, we evaluated matrix metalloproteinase-2 (MMP)-2 and 9, vascular endothelial growth factor (VEGF)-A, Cluster of Designation (CD) 31, CD38 and interleukine (IL)-10. An in vitro experiment showed that heat-inactivated C57BL/6 serum had significantly lower cytotoxic effects on BALB/c-derived CT26 cells than intact C57BL/6 serum or BALB/c serum. In vivo experiments revealed that tumor size, HIF-1α, MMP-2, and MMP-9 levels were significantly lower in the experimental group than in the control group. In contrast to control animals, allogeneic serum treatment led to marked reductions in CD31, VEGF-1, CD38, and IL-10 levels. A new approach to serum or plasma therapy and allogeneic vaccines for cancer is intra-tumor injection of allogeneic serum. In light of the ease and availability of allogeneic immunotherapies, allogeneic serum and plasma therapy could potentially be used as an alternative monotherapy or in combination with other therapies.
Keywords: Allogeneic serum, Angiogenesis, Cluster of designation 38, Hypoxia-inducible factor 1, Alpha subunit, Interleukin-10, Matrix metalloproteinases -
Background
While several antivirals have been considered among the candidate repurposed drugs against SARS-CoV-2 infection, limited evidence exists on Atazanavir/Ritonavir.
ObjectivesThis trial was designed to assess the efficacy of Atazanavir/Ritonavir compared to Lopinavir/Ritonavir, another antiretroviral drug investigated in the previous studies.
MethodsThis randomized, double-blind clinical trial was conducted on hospitalized patients with laboratory or confirmed SARS CoV-2 infection. Patients were randomly assigned (1:1) to receive either Lopinavir/Ritonavir (200mg Lopinavir+50mg Ritonavir, twice a day) or Atazanavir/Ritonavir (300mg Atazanavir+100 mg Ritonavir, once a day) for up to 14 days during their admission along with the standard care. The primary endpoint was total all-cause death in all patients during the hospitalization period. Secondary outcomes included length of hospitalization.
ResultsOut of 103 adults included in the analysis 54 and 49 were assigned to Atazanavir/Ritonavir and Lopinavir/Ritonavir groups, respectively. The occurrence of adverse effects, defined as symptoms attributed to the drugs which no longer appear upon the cessation of the drug, was higher for cardiac side effects in Atazanavir/Ritonavir group. No statistically significant difference was observed between the two groups in terms of the length of hospitalization. After adjustment for other covariates in the study, treatment with Atazanavir/ritonavir did not result in a significant reduction in mortality compared to treatment with Lopinavir/Ritonavir.
ConclusionThe efficacy of Atazanavir/Ritonavir in this preliminary study was not superior to Lopinavir/Ritonavir in reducing mortality and length of hospitalization in COVID-19 patients. However, the limited efficacy of both compounds does not support their use in primary care for COVID-19 patients.
Keywords: Atazanavir, COVID-19, Lopinavir, Ritonavir, Randomized Clinical Trial, SARS-CoV-2 -
زمینه و اهداف
عفونت های سودوموناس آیروژینوزا مقاوم به آنتی بیوتیک معمولا سخت درمان می شوند و آنتی بیوتیک های محدودی برای درمان وجود دارد. مقاومت این ارگانیسم نسبت به عوامل ضد میکروبی در حال افزایش است و فاکتورهای بیماریزای آن نیز مشخص شده است. لذا در این مطالعه کوتاه، اثر سینرژیسم نانوذره نقره و اریترومایسین علیه سودوموناس آیروژینوزا دارای اگزوتوکسین A جدا شده از ترشح زخم های سوختگی بررسی شد.
مواد و روش کاردر این مقاله کوتاه، 40 نمونه از محل ترشح زخم های سوختگی با سواپ گرفته شد و با انجام تست های تشخیصی و افتراقی استاندارد 26 نمونه سودوموناس آیروژینوزا جدا گردید. وجود ژن اگزوتوکسین A با روش PCR و الگوی مقاومت آنتی بیوتیکی با روش کربی بایر ارزیابی شد. سپس اثر مخلوط نانو ذره نقره و اریترومایسین در 10 رقت برای بررسی حداقل غلظت مهارکنندگی به صورت میکرودیلوشن و مقایسه با نتایج الگوی مقاومت آنتی بیوتیکی استفاده شد.
یافته ها و نتیجه گیریاز 26 نمونه سودوموناس آیروژینوزا 25 نمونه واجد ژن اگزوتوکسین A بودند. برای حداقل غلظت مهاری، این باکتری نسبت به نانو ذرات نقره حساس و نسبت به اریترومایسین مقاوم بود. در آخر اینکه هیچ گونه همکاری بین این دو ماده برای مهار این باکتری وجود نداشت.
کلید واژگان: نانو ذرات نقره, سودوموناس آئئروژینوزا, اریترومایسین, حداقل غلظت مهاری, اگزوتوکسین ABackgroundPseudomonas aeruginosa infections are resistant to antimicrobial agents and produce toxic virulence factors such as exotoxin A. Studies have shown that some nanoparticle compounds and antibiotics have a synergistic effect. Therefore, the aim of this study was to investigate the synergistic effect of silver nanoparticles and erythromycin on antibiotic-resistant P. aeruginosa.
Materials & MethodsIn this descriptive cross-sectional study, 40 cultured samples of burn wound secretions were taken from Imam Musa Kazem (PBUH) Burns Hospital in Isfahan, Iran. Diagnostic and differential tests were performed. Antibiogram was performed to obtain the bacterial resistance pattern and the exotoxin A gene was detected by PCR. The bacterial minimum inhibitory concentration (MIC) was then applied to the silver nanoparticles (shape and mean size) and erythromycin separately and a common mixture of both in 10 dilutions to investigate the synergistic effect.
Results & ConclusionA number of 26 bacteria were strains of P. aeruginosa. Of samples, 25 (96.15%) had exotoxin A gene. All samples were sensitive to all erythromycin concentrations. The mean MIC of nanoparticles against bacteria was reported to be 2 μg/mL. A solution of 40 μg/mL erythromycin and 2 μg/mL nanoparticles was also considered as MIC solution. Pseudomonas aeruginosa is sensitive to erythromycin to very low concentrations of silver particles. But no synergistic effect between silver nanoparticles and erythromycin was reported for this bacterium. Based on PCR results and antibiotic resistance pattern, a significant number of the samples contained the exotoxin A gene and the use of erythromycin alone was not appropriate for treatment.
Keywords: Silver nanoparticles, Pseudomonas aeruginosa, Erythromycin, Minimum Concentration, Exotoxin A
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