Synergistic Effects of Quercetin-modified Silicone Gel Sheet in Scar Treatment

Both silicone gel and quercetin are effective in scar treatment but have different action mechanisms. Quercetin is mainly applied in the gel form and can lead to poor adhesion of silicone gel sheet; therefore, they cannot be combined in clinical use. In this study, a silicone gel sheet that releases quercetin in a sustained manner for 48 hours was successfully developed. Four round scars (Ø: 1 cm) were made in the ears of New-Zealand albino rabbits (n=10). After scar healing, the rabbits were divided into four groups: blank control group with no treatment, silicone gel sheet group with dressing change every 2 days, quercetin group with dressing change 3 times daily, and combination treatment group with dressing change every 2 days. Scar assessment was performed 3 months later. Transepidermal water loss showed no difference between the combination treatment group and the silicone gel sheet group, but was lower than that in the quercetin group and the blank control group. Immunohistochemistry of CD 31 and proliferating cell nuclear antigen showed the following results: combination treatment group < silicone gel sheet group = quercetin group < blank control group. Polymerase chain reaction results showed that the expression of type-I and type-III collagen in the combination treatment group and the quercetin group was significantly lower than that in the other two groups. Thus, quercetin-modified silicone gel sheet combines the advantages of the two treatments and is more effective at inhibiting cell proliferation in scar tissue than either of the two treatments alone.

The new Epoch of Antithrombotic Therapy in the Long-Term Prevention of a non-Cardioembolic Stroke

This article presents current opinions on the role of antithrombotic therapy in secondary prevention of cardiovascular diseases (CVD) in patients after noncardioembolic stroke or a transient ischemic attack on the background of sinus rhythm. This review analytically analyses evidence-based data on antithrombotic drugs used for this secondary prevention. Despite the fact that acetylsalicylic acid (ASA) is still a “gold standard” for prevention of noncardioembolic stroke, the search for rational combinations of antithrombotic drugs to increase the effectiveness of preventive treatment is relevant. The question whether the rivaroxaban treatment as monotherapy or in combination with ASA is more effective than the ASA monotherapy for secondary prevention of cardiovascular complications (CVC) was addressed in the COMPASS study. In that study, three regimens of antithrombotic therapy were compared in patients with stable atherosclerotic CVD: rivaroxaban (2.5 mg twice a day) in combination with ASA (100 mg/day); rivaroxaban (5 mg twice a day); and ASA (100 mg/day). Risk for development of major CVC (death, stroke, myocardial infarction (IM)) was lower (p<0.001) in the rivaroxaban+ASA combination treatment group than in the ASA monotherapy group; however, the risk of major bleedings was somewhat higher. Total risk based on the definition of “pure clinical benefit” was lower for the rivaroxaban+ASA combination treatment than for the ASA monotherapy. The rivaroxaban monotherapy did not result in a significant decrease in the risk of major CVC compared to the ASA monotherapy but significantly increased the risk of major bleedings. Incidence of repeated ischemic stroke for a year was 1.1% for the combination therapy, 2.6% for the rivaroxaban therapy, and 3.4% for the ASA monotherapy with significant differences between the combination treatment group and the ASA monotherapy group (p<0.01). Relative risk of repeated stroke was 67% lower for the combination therapy group compared to the ASA monotherapy group. The combination of rivaroxaban (2.5 mg twice a day) and ASA (100 mg) opens a new epoch of antithrombotic treatment for primary and secondary prevention of stroke in patients with a stable atherosclerotic CVD and sinus rhythm.

A Treatment Combined Prussian Blue Nanoparticles With Low-intensity Pulsed Ultrasound Alleviates Cartilage Damage in Knee Osteoarthritis by Initiating PI3K/Akt/mTOR Pathway

Background: Reactive oxidative stress (ROS) related apoptosis in chondrocytes and extracellular matrix (ECM) degradation play crucial roles in the process of osteoarthritis (OA). Prussian blue nanoparticles (PBNPs) are known to scavenge ROS in cellular. Low-intensity pulsed ultrasound (LIPUS) has been used as a non-invasive modality for the is widely used in clinical rehabilitation management of OA. Methods: In this study, we aim to investigate the effects of PBNPs/LIPUS combined treatment on knee osteoarthritis (KOA) and to determine whether phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway mediates this process. Use LPS to process primary cells of knee joint cartilage to establish a cartilage knee arthritis model. After treated with LIPUS and PBNPs, cell viability was rated by CCK-8 and ROS levels were assessed by DCFH-DA. Cell apoptosis was estimated by flow cytometry and TUNEL staining. Articular pathological changes were observed by naked eyes, H&E, and Safranin O staining, then monitored by cartilage lesion grades and Mankin’s score. Protein levels of cleaved caspase-3, Bcl-2, Bax, p-PI3K, PI3K, p-Akt, Akt, p-mTOR, mTOR, IL-1β, MMP3, MMP13, p-JINK, JINK, p-c-Jun, and c-Jun were subjected to western blot. Results: Cellular ROS, apoptosis rate, and TUNEL staining of chondrocytes were fairly decreased in the PBNPs group and the LIPUS group but drastically down-regulated in the PBNPs/LIPUS combination treatment group when compared with the LPS group. Both PBNPs and LIPUS decreased the grades of cartilage lesions and Mankin scores of knee articular cartilage, while combined administration achieved more reduction. Western blot results showed that the cleaved caspase-3, Bax, IL-1β, MMP3 and MMP13 in the PBNPs and LIPUS groups slightly decreased, and Bcl2 increased slightly, while in the combination treatment group, the former was significantly decreased, and Bcl2 was Significantly increased. Conclusion: The PBNPs/LIPUS combination treatment increased protein levels of p-PI3K, p-Akt, and p-mTOR but decreased the protein levels of p-JINK and p-c-Jun, in vitro and vivo. The PBNPs/LIPUS combination treatment reduced cellular ROS, apoptosis, and matrix metalloproteinases (MMPs), as a consequence, alleviated articular cartilage damage in KOA. Moreover, the PBNPs/LIPUS combination treatment suppressed the JINK/c-Jun signal pathway.

Efficacy and Tolerability of Probenecid as Urate-lowering Therapy in Gout; Clinical Experience in High-prevalence Population

Objective.Probenecid is recommended as urate-lowering therapy (ULT) in patients with gout where xanthine oxidase inhibitors are ineffective, not tolerated, or contraindicated. The aim of our study was to determine the efficacy of probenecid to achieve serum urate (SU) targets (< 0.36 mmol/l) in clinical practice.Methods.We identified 57 patients prescribed with probenecid from a database of 521 rheumatology clinic attenders with gout. Demographic characteristics, indications for probenecid, probenecid doses, side effects, and laboratory data including estimated glomerular filtration rate (eGFR) and SU were recorded.Results.There were 30/57 (53%) patients treated with probenecid as monotherapy and 27/57 (47%) patients treated with probenecid in combination with allopurinol. Target SU concentrations (< 0.36 mmol/l) were achieved in 10/30 (33%) of the probenecid monotherapy group and 10/27 (37%) of the combination treatment group. Baseline SU concentrations, but not eGFR or probenecid dose, independently predicted achievement of target SU. Target SU was achieved in 5/15 (33%) patients with eGFR < 50 ml/min/1.73 m2. There was no difference in the percentage of patients achieving SU target in those with eGFR < 50 ml/min/1.73 m2 compared with those with eGFR ≥ 50 ml/min/1.73 m2. Adverse events attributed to probenecid were observed in 8/42 (19%) patients with eGFR ≥ 50 ml/min/1.73 m2 and in 2/15 (13%) patients with eGFR < 50 ml/min/1.73 m2.Conclusion.Probenecid has moderate efficacy as ULT in clinical management of patients with complex gout who have a lack of efficacy or intolerance to allopurinol. Patients with chronic kidney disease may respond to probenecid with similar rates of adverse events.

A Community-Based Clinic Survey of Antidepressant Use in Persons with Schizophrenia

Objective: To determine the rates of antidepressant and antipsychotic use in the treatment of schizophrenia. Method: The primary therapists at 8 community mental health centres in a metropolitan Canadian city completed a survey questionnaire for all of their active clients. Information was collected about diagnoses, medication treatments, and clinical variables. Results: There were 3555 clients, 1552 (43.7%) of which had a diagnosis of schizophrenia. Of clients with schizophrenia, 94% were prescribed antipsychotic medications, and 11.6% of these were also prescribed antidepressant medications. There were differences between the combination-treatment group and the antipsychotic-alone group in gender ratio, rates of concurrent diagnoses of mood disorder, level of current functioning, and total number of hospitalizations. Conclusion: In this community-based sample of clients with schizophrenia, antidepressants and antipsychotics are commonly prescribed in combination, even though the rate of concurrent mood disorders diagnoses is low. Further studies should clarify the efficacy and indications for antidepressant use in this population.

Comparative Efficacy and Safety of Terfenadine with Pseudoephedrine and Terfenadine alone in Allergic Rhinitis

A randomized, double-blind clinical trial was conducted on 41 adult patients to compare the efficacy and safety of the combination of terfenadine and pseudoephedrine with that of terfenadine alone. Efficacy of treatment evaluated by the physician and patients showed an excellent rating in 45.45% patients in the combination treatment group compared with an excellent rating in 10.53% in the single treatment group. The difference between both treatments was statistically significant, with a z value of 1.660 ( p < 0.05). The combination of terfenadine and pseudoephedrine was found to result in faster relief in a greater number of patients than terfenadine alone. However, both drugs were well tolerated.

Graded compression Stockings with and without Heparin-Dihydroergotamine in the Prevention of Deep Venous Thrombosis following Elective Hip Alloplasty

Two hundred and five patients scheduled for total hip alloplasty were randomized to one of the following two regimes, in order to prevent postoperative thromboembolism. (1) Graded compression stockings and heparin 5000 iu/dihydroergotamine 0.5 mg twice a day subcutaneously. (2) Graded compression stockings and placebo twice a day subcutaneously. Screening for deep venous thrombosis (DVT) was carried out by 99mTc-plasmin scintimetry and whenever this was indicative for DVT, ascending phlebography was performed. The definitive criteria for DVT were intraluminal filling defects on phlebography. If DVT was diagnosed, pulmonary perfusion/ventilation scintigraphy was performed. In the group receiving heparin/dihydroergotamine 11 of 96 patients (11%) developed DVT and in the placebo group 25 of 109 patients (23%) developed DVT (P < 0.05). One patient in the combination treatment group and seven patients in the placebo group developed pulmonary embolism ( P < 0.05). It is concluded that the combination of graded compression stockings, low dose heparin and dihydroergotamine is superior to graded compression stockings alone in preventing thromboembolism following total hip alloplasty.