Dihydrotanshinone I Specifically Inhibits NLRP3 Inflammasome Activation and Protects Against Septic Shock In Vivo

The abnormal activation of the NLRP3 inflammasome is closely related to the occurrence and development of many inflammatory diseases. Targeting the NLRP3 inflammasome has been considered an efficient therapy to treat infections. We found that dihydrotanshinone I (DHT) specifically blocked the canonical and non-canonical activation of the NLRP3 inflammasome. Nevertheless, DHT had no relation with the activation of AIM2 or the NLRC4 inflammasome. Further study demonstrated that DHT had no influences on potassium efflux, calcium flux, or the production of mitochondrial ROS. We also discovered that DHT suppressed ASC oligomerization induced by NLRP3 agonists, suggesting that DHT inhibited the assembly of the NLRP3 inflammasome. Importantly, DHT possessed a significant therapeutic effect on NLRP3 inflammasome–mediated sepsis in mice. Therefore, our results aimed to clarify DHT as a specific small-molecule inhibitor for the NLRP3 inflammasome and suggested that DHT can be used as a potential drug against NLRP3-mediated diseases.

The Effect of Ceftriaxone in Valproic Acid-Induced Mouse Model of Autism

Purpose: Autism is a multifactorial neurodevelopment disease and it has not been disclosed as a hypoglutamatergic or hyerglutamathergic disease. Ceftriaxone is an antibiotic that increases GLT-1 expression in the brain in chronic use. In our study we aimed to investigate the effects of different doses of ceftriaxone in postnatal period in male mice exposed to valproic acid (VPA) at 12.5th day of pregnancy. Material and Methods: A total of 96 Balb/c male mice were divided into 12 groups (n=8 animals per group). Ceftriaxone (50, 100, 200 mg/kg/day) or saline was given to the male offsprings born from pregnant mice administered VPA and/or saline, between days 47 and 55. Dihydrokainic acid (10 mg/kg), a glutamate transporter-1 (GLT-1) inhibitor, was administered intraperitoneally to evaluate whether GLT-1 mediates the effect of ceftriaxone. Three chamber sociability and social interaction test and the rota rod test were performed in all groups on days 54 and 55. GLT-1 levels in the hippocampus were measured by immunohistochemistry and western blotting. Results: In our study, autism-like behaviors were observed in male offspings that were exposed to VPA in the intrauterine period. Chronic ceftriaxone administration has no curative effect on behavioral impairment seen in autism. Conclusion: Our results show that ceftriaxone did not exert significant therapeutic effect on valproic acid-induced mouse model of autism.

Evaluation of pediatric patients with јuvenile idiopathic arthritis treated with biological therapy Tocilizumab (Actemra)

Juvenile idiopathic arthritis (JIA) is the most common chronic disease in childhood. It manifests a heterogenic group of symptoms of arthritis, lasting at least 6 weeks and it appears before the age of 16. Patients who had no good therapeutic response to conventional therapy with Methotrexate were treated with biological therapy. The aim of this paper was to evaluate 9 patients who were receiving Tocilizumab at the Department of Rheumocardiology, University Clinic of Pediatric Diseases in Skopje. Materials and methods: Our study included 9 patients treated at our Department with biological therapy with Tocilizumab. Prior to initiation of the biological therapy, all patients underwent laboratory investigations, purified protein derivative (PPD) skin test for tuberculosis, X ray of the lungs and heart, and analysis of hepatitis markers. All patients were treated with amp. Actemra (tocilizumab) 8 mg/kg/tt i.v. Two of the patients had a severe form of the disease (one with severe systemic form and one with severe oligoarticular form of JIA). All presented patients had clinical remission of the disease. Conclusion: Therapy with tocilizumab in patients with juvenile idiopathic arthritis is a good therapeutic choice. The results obtained in our study have shown a significant therapeutic effect of tocilizumab even in severe forms of the disease.

The Clinical Effect of Moxifen Tablets Combined with Medroxyprogesterone Acetate Injection on Patients with Endometriosis

Objective: To explore the clinical effect of moxifen tablets combined with medroxyprogesterone acetate injection on patients with endometriosis. Methods: 90 patients with endometriosis from August 2018 to March 2019 were randomly divided into control group and observation group, with 45 cases in each group. The control group was treated with moxifene tablets and the observation group with medroxyprogesterone acetate. The changes of serum sex hormone, P, CA125 levels, adverse reactions and therapeutic effects were compared between the two groups. Result: Before treatment, there was no significant difference in serum sex hormone and P, CA125 levels between the two groups (P > 0.05); after treatment, the indexes of the two groups were reduced, and the LH, E2, FSH, CA125 and P water in the observation group were lower than those in the control group (P < 0.05); the curative effect of the observation group was significantly better than that in the control group (P < 0.05); the incidence of adverse reactions in the observation group was lower than that in the control group (P < 0.05). Conclusion: Moxifene combined with medroxyprogesterone acetate has a significant therapeutic effect on endometriosis. It can significantly reduce the level of serum sex hormone. The incidence of adverse reactions is low and the treatment safety is high. It is worth popularizing.

Clinical Features of Severe Tsutsugamushi Disease Complicated with Hemophagocytic Lymphohistiocytosis

The article discusses a case of severe tsutsugamushi disease complicated with hemophagocytic syndrome in Guangdong Maternal and Child Health Hospital and concludes that blood purification technology has significant therapeutic effect among children with severe HLH complicated with multiple organ dysfunction.

Nanoencapsulation of Polyphenols as Drugs and Supplements for Enhancing Therapeutic Profile - A Review

: Polyphenolic phytoconstituents have been widely in use worldwide since ages and are categorised as secondary metabolites of plants. The application of polyphenols such as quercetin, resveratrol. curcumin as nutritional supplement has been researched widely. The use of polyphenols, and specifically quercetin for improving the memory and mental endurance have shown significant effects among rats. Even though similar results has not been resonated among human but encouraging preclinical results have encouraged researchers to explore other polyphenols to study the effects as supplements among athletes. The phytopharmacological research has elucidated the use of natural polyphenols to prevent and treat various physiological and metabolic disorders owing to its free radical scavenging properties, anti-inflammatory, anti-cancer and immunomodulatory effects. In spite of the tremendous pharmacological profile, one of the most dominant problem regarding the use of polyphenolic compounds is their low bioavailability. Nanonization is considered as one of the most prominent approaches among many. This article aims to review and discuss the molecular mechanisms of recently developed nanocarrier-based drug delivery systems for polyphenols and its application as drugs and supplements. Nanoformulations of natural polyphenols are bioactive agents, such as quercetin, kaempferol, fisetin, rutin, hesperetin, and naringenin epigalloccatechin-3-gallate, genistein, ellagic acid, gallic acid, chlorogenic acid, ferulic acid, curcuminoids and stilbenes is expected to have better efficacy. These delivery systems are expected to provide higher penetrability of polyphenols at cellular levels and exhibit a controlled release of the drugs. It is widely accepted that natural polyphenols do demonstrate significant therapeutic effect. However, the hindrances in their absorption, specificity and bioavailability can be overcome using nanotechnology.

Fixed-Dose Combination of NSAIDs and Spasmolytic Agents in the Treatment of Different Types of Pain—A Practical Review

This review presents the most common disease entities in which combinations of NSAIDs and spasmolytic drugs are used to reduce pain. The benefits of fixed-dose combination products (FDCs) are that they improve the response in people with insufficient monotherapy. Using the synergy or additive effect of drugs, it is possible to obtain a significant therapeutic effect and faster action with the use of smaller doses of individual drugs. In addition, one active ingredient may counteract adverse reactions from the other. Another essential aspect of the use of FDCs is the improvement of medical adherence due to the reduction in the pill burden on patients. It is also possible to develop a fixed-dosed combination product de novo to address a new therapeutic claim and be protected by patents so that the manufacturer can obtain exclusive rights to sell a particular FDC or a formulation thereof. The proposed fixed-dose combinations should always be based on valid therapeutic principles and consider the combined safety profile of all active substances included in the medicinal product. This review aims to identify which combinations of NSAIDs and spasmolytics have been developed and tested and which combinations are still under development.

KINESITHERAPY AND ULTRASOUND IN CHILDREN WITH BRONCHIAL ASTHMA

Introduction:- There are no studies in the literature on the combination of kinesitherapy and ultrasound in children with bronchial asthma. Objective:- To compare the effect of the combination of kinesitherapy and ultrasound in children with bronchial asthma compared to a control group without rehabilitation. Material and methods:- 24 children (age 9.63 ± 3.56 years) with bronchial asthma were followed for 10 days (5 days as inpatients and 5 days as outpatients). They were randomized into two identical groups - physiotherapeutic and control. Both groups were treated with standard pharmacotherapy. The physiotherapy group was further treated with kinesitherapy and ultrasound. Spirometric and anthropometric parameters were recorded at the beginning and end of the therapeutic course. The ratios between actual and expected spirometric parameters, adjusted for all anthropometric parameters, were included in the statistical analysis. Results:- In both groups, the ratios between the actual and the expected spirometric parameters improved significantly after 10 days of treatment compared to before (P<0.05). The improvement after treatment was significantly greater in the physiotherapeutic compared to the control group (P<0.05). Conclusion:- In the 10-day treatment of children with bronchial asthma, the combination of kinesitherapy and ultrasound has a significant therapeutic effect, building on that of pharmacotherapy.

Veillonella parvula: a strictly anaerobic bacterium with high efficacy for safe and specific tumor targeting and colonization

Bacterial cancer therapy has gained lots of attention in the past decade and is now considering a reliable option for the future. However, some concerns have limited its application into clinic settings like insufficient colonization of tumors and infectious origin of the currently used bacteria. Veillonella parvula (V. parvula) as a strictly anaerobic bacterium which has rarely identified as a pathogen in human, was intravenously administrated into 4T1 breast tumor-bearing BALB/c mice. V. parvula exhibited significant tumor-targeting and colonization efficacy, 24 h after administration and formed clustered colonies at the tumors’ central region. The normal organs became completely clear from the bacteria after 72 h, and no side effects or death were observed at the animals after administration of V. parvula. Although mean tumor volumes in the V. parvula treated group was lower than the control (~ 25.4%), their difference wasn’t statistically significant (P > 0.05). Despite significant tumor colonization (5500000:1 in comparison with normal organs), V. parvula didn’t cause a significant therapeutic effect on the metastasis or survival time of tumor-bearing mice. Taking together, V. parvula is a completely safe and tumor-specific targeting agent per se, without any genetic manipulation.

Results of the use of cladribine in children with acute myeloid leukemia in the treatment according to the AML-MM-2006 protocol

The aim of this work was to evaluate the results of the use of cladribine in the treatment according to the AML-MM-2006 protocol as post-remission therapy in children. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The article presents the experience of treating children with AML at the Russian Children's Clinical Hospital, and later at the Dmitry Rogachev National Research Center within the framework of the AML-MM-2006 protocol. For the period from 2006 to 2018, 25 children were included in the study. As a comparison, to assess the effectiveness of therapy, the remaining cohort of patients from the intermediate risk group, which consisted of 83 children, was selected. Ultimately, the addition of cladribine in consolidation therapy did not show a significant therapeutic effect (event-free survival 0.47 ± 0.1 for the cladribine group, 0.52 ± 0.06 for the control group), including the development of relapse (56% patients in the cladribine group had a relapse, in the control group – in 34.5%). Thus, the study proved that further inclusion of cladribine in consolidation therapy for primary AML is inappropriate.