Current Therapeutic Research-clinical and Experimental最新文献

Background

Although controversial, experimental data suggest the use of propofol may be associated with neurotoxicity. The mechanisms responsible for propofol neurotoxicity in animals are not yet clear.

Objective

This study aimed to determine the effects of propofol on the proliferation of neural stem cells in rat hippocampus and the mechanisms underlying these effects.

Methods

Forty-five adult male Sprague-Dawley rats were randomly divided into 5 groups: Control (N group), intralipid (V group), 30 mg/kg propofol (Prop30 group), 60 mg/kg propofol (Prop60 group), and 120 mg/kg propofol (Prop120 group). The rats in all groups received 5, once daily intraperitoneal injections. For each of the 5 days, the N group received 6 mL/kg normal saline, the V group received 6 mL/kg fat emulsion, the Prop30 group received 30 mg/kg propofol, the Prop60 group received 60 mg/kg propofol, and the Prop120 group received 120 mg/kg propofol. Memory function was scored daily using the Morris water maze test. Immunofluorescence staining was used to histologically monitor the proliferation and differentiation of the rats’ hippocampal neural stem cells, and real time quantitative polymerase chain reaction and Western blotting were used to determine the expression of Notch3, Hes1, and Hes5.

Results

Compared with the N group, the Prop120 group exhibited reduced learning and memory, whereas there were no significant differences for the Prop60 group. The number of β-tubulin III⁺ cells increased in the Prop60 group, but decreased in the Prop120 group. Compared with the N group, the relative expression of Notch3 and Hes5 increased significantly in the Prop60 group, whereas this expression decreased in the Prop120 group.

Conclusions

These data demonstrate that repeated, subchronic (5 days) intraperitoneal injections of 60 mg/kg propofol can effectively promote rat hippocampal neural stem cells proliferation and differentiation, and that this is likely mediated by its effects on the Notch3-Hes5 pathway.

Background

Multiple sclerosis (MS) is a chronic autoimmune disease. Current medications have some limitations such as low efficacy and high side effects. In recent years, statins have been raised as potential therapeutics for MS treatment with minimal complications. In addition, patient monitoring using suitable molecular markers is necessary for treatment response evaluation.

Objective

The aim of the present study was the evaluation of SIRT1 gene expression changes following rosuvastatin therapy in patients with MS.

Methods

This before–after uncontrolled clinical trial study was performed on 25 patients with MS. Patients were treated with 20 mg rosuvastatin daily for 3 months. The Expanded Disability Status Scale (EDSS) was measured before and after statin therapy. Blood samples were taken from patients 2 times, before and after statin therapy, and centrifuged for white blood cell isolation. Total RNA was extracted using RNX-plus reagent, and complementary DNA was synthesized using Pars Tous cDNA Synthesis Kit. Real-time polymerase chain reaction was done using SYBR blue master mix and gene-specific primers in Roche light cycler. Patients’ information was recorded using a checklist. Data analysis was performed using SPSS version 23 and Graph Pad version 9 software and P < 0.05 was considered a significant level.

Results

SIRT1 was significantly upregulated in MS patients after statin therapy. Subsequently, EDSS of patients was decreased along with the increase in SIRT1 gene expression, although EDSS changes were not significant (P > 0.05). Pearson correlation test showed no significant relationship between EDSS and SIRT1 gene expression (P > 0.05). No significant relationship was observed between SIRT1 expression or EDSS levels with patients’ age, sex, weight, height, and body mass index and administrated drugs (P > 0.05).

Conclusions

SIRT1 potentially is a sensitive and reliable biomarker for patients with MS monitoring during statin therapy.

Background

Sexuality is a natural component of human behavior. The general population has been extensively studied since the first half of the 20th century. On the other hand, regarding patients treated for schizophrenia, discussing sexual disorders was initially considered inappropriate because it was believed they should not be sexually active. Given these findings, this work proposes to study the sexuality of patients with schizophrenia.

Objectives

Our objectives were to assess the sexuality of patients with schizophrenia, to identify factors associated with sexual dysfunction among these patients, and to determine practitioners' attitudes toward the sexuality of our study population.

Methods

This is a cross-sectional study carried out in the Psychiatry Department of Kairouan (outpatient department), including 46 patients diagnosed with schizophrenia. A pre-established information sheet was completed for each patient recruited, including sociodemographic and clinical data; on the other hand, 3 scales ensured a sexual psychometric evaluation: Psychotropic-Related Sexual Dysfunction Questionnaire, Arizona Sexual Experiences Scale, and Changes in Sexual Functioning Questionnaire-Male Clinical Version.

Results

Concerning the evaluation of sexuality according to the scales used, sexual dysfunction according to Psychotropic-Related Sexual Dysfunction Questionnaire scores was observed in 31 patients (67.4%). According to Arizona Sexual Experiences Scale scores, 24 patients (52%) had a sexual dysfunction, and for the total score of the Changes in Sexual Functioning Questionnaire-Male Clinical Version, 27 patients (58.7%) had a sexual dysfunction. We cannot confirm the existence of a relationship between the dose of the current treatment (in chlorpromazine equivalent) used and the results of the test assessing sexuality. In addition to these results, we can deduce the existence of a statistically significant association between the antipsychotic agent used and the results of the Psychotropic-Related Sexual Dysfunction Questionnaire only.

Conclusions

We recommend that screening for sexual dysfunction in patients followed for schizophrenia should be systematic, regardless of the antipsychotic molecule type and dosage. In this regard, we recommend the establishment of a better therapeutic relationship between caregivers and patients with schizophrenia, based on empathy and trust, so that the latter feel comfortable enough to address the sexual dimension in general and sexual dysfunction in particular.

Background

Schistosomiasis is an acute and chronic parasitic disease caused by blood flukes of the genus Schistosoma. The current drugs for treating schistosomiasis are associated with some side effects.

Objective

The aim of this systematic study was an overview of the treatment of diseases caused by Schistosoma based on nanoparticles.

Methods

In the present systematic research with keywords “Schistosoma”, “parasitism”, “anti-Schistosoma activity”, “nanoparticles”, “metal nanoparticles”, “silver nanoparticles”, “gold nanoparticles”, “polymer nanoparticles”, “PLGA nanoparticles”, “nanoemulsions”, “in vitro”, and “in vivo” from five English-language databases, including ScienceDirect, europePMC, PubMed, Scopus, Ovid, and Cochrane were searched from 2000 to 2022 by 2 researchers.

Results

In the initial search, 250 studies were selected. Based on the inclusion and exclusion criteria, 27 articles were finally selected after removing duplicate, unrelated, and articles containing full text. In present article, the most nanoparticles used against Schistosoma were gold nanoparticles (22%).

Conclusions

The results indicate the high potential of various nanoparticles, including metal nanoparticles, against Schistosoma. Also, the remarkable anti-schistosomal activity of nanoparticles suggests their use in different fields to eliminate this pathogenic microorganism so that it can be used as an effective candidate in the preparation of anti-schistosomal compounds because these compounds have fewer side effects than chemical drugs. Ther Res Clin Exp. 2023; XX:XXX–XXX).

Background

Opioid-induced constipation (OIC) may increase the risk of fecal impaction and mortality in patients with advanced illness. Methylnaltrexone (MNTX) is efficacious for OIC.

Objective

The purpose of this analysis was to evaluate cumulative rescue-free laxation response with repeat MNTX dosing in patients with advanced illness who were refractory to current laxative regimens and to assess the influence, if any, of poor functional status on response to MNTX treatment.

Methods

This analysis included pooled data from patients with advanced illness and established OIC who were on a stable opioid regimen in a pivotal, randomized, placebo (PBO)-controlled clinical trial (study 302 [NCT00402038]) or a randomized, PBO-controlled Food and Drug Administration-required postmarketing study (study 4000 [NCT00672477]). Patients in study 302 received subcutaneous MNTX 0.15 mg/kg or PBO every other day, whereas those in study 4000 received MNTX 8 mg (body weight ≥38 to <62 kg), MNTX 12 mg (body weight ≥62 kg), or PBO every other day. Outcomes included cumulative rescue-free laxation rates at 4- and 24-hours postdose for the first 3 doses of study drug and time to rescue-free laxation. To assess if functional status influenced treatment outcomes, we performed a secondary analysis on the outcomes stratified by baseline World Health Organization/Eastern Cooperative Oncology Group performance status, pain scores, and safety.

Results

One hundred eighty-five patients received PBO and 179 patients received MNTX. The median age was 66.0 years, 51.5% were women, 56.5% had a baseline World Health Organization/Eastern Cooperative Oncology Group performance status score >2, and 63.4% had a primary diagnosis of cancer. Cumulative rescue-free laxation rates were significantly higher with MNTX than PBO 4- and 24-hours after doses 1, 2, and 3 (P < 0.0001), and between-treatment comparisons remained significant (P < 0.0001) regardless of performance status. The estimated time to first rescue-free laxation was shorter for patients receiving MNTX versus PBO. No new safety signals were identified.

Conclusions

Repeated use of MNTX represents a safe and effective treatment for OIC in patients with advanced illness regardless of baseline performance status. ClinicalTrials.gov identifier: NCT00672477. (Curr Ther Res Clin Exp. 2023; 84:XXX–XXX)

© 2023 Elsevier HS Journals, Inc.

Background

A group of Italian experts in impetigo medical care sought to define 10 statements to describe the ideal characteristics of the best local antibiotic treatments, and to provide relevant information re- garding their appropriate use and prescription that should be considered in clinical practice for impetigo management.

Objective

A group of Italian experts in impetigo medical care sought to define 10 statements to describe the ideal characteristics of the best local antibiotic treatments, and to provide relevant information regarding their appropriate use and prescription that should be considered in clinical practice for impetigo management.

Methods

A consensus on ideal features of antibiotic therapy for the treatment of impetigo was appraised by an online Delphi-based method, based on a panel of 61 infectious disease specialists, pediatricians, and dermatologists coordinated by a scientific committee of 5 experts specializing in impetigo management.

Results

Full or very high consensus was reached on the 10 statements identified to describe the characteristics of the best hypothetic antibiotic therapy for impetigo together with indications for appropriate antibiotics use.

Conclusions

Several criteria have to be considered when selecting topical antibacterial therapy for impetigo. Beyond efficacy and safety, antimicrobial susceptibility and pharmacological characteristics of the agent are essential points. Formulation of the antimicrobial product is fundamental, as well as patient and caregiver preference, to facilitate therapeutic adherence, to achieve the infection control, and to obtain the best benefit from treatment (Curr Ther Res Clin Exp. 2023; 84:XXXXXX).

Background

Many natural products have immunomodulatory properties. However, the mechanism of immunomodulatory activities are poorly understood.

Objectives

This study evaluated the influence of bovine colostrum products, a whey product, or their combinations with other natural products on human peripheral blood mononuclear cells’ (PBMC) ability to produce cytokines upon activation.

Methods

PBMCs were pretreated with ultrafiltered colostrum, nano-filtered bovine colostrum, egg yolk extract, a botanical blend, colostrum + egg yolk extract, colostrum + egg yolk + botanical blend, and fermented whey and then stimulated with lipopolysaccharide or phytohemagglutinin. Cytokine production was measured by the Luminex assay.

Results

All study products demonstrated immunomodulatory properties by regulating cytokines production by activated PBMCs. Ultrafiltered colostrum alone displayed the highest immune stimulatory activity. It stimulated proinflammatory cytokine production by lipopolysaccharide-activated PBMCs and suppressed cytokine production by phytohemagglutinin-activated cells. Other study products mainly suppressed cytokine release by both cell types. The immunomodulatory properties depended upon the dose of the products used in the study.

Conclusions

All tested products modulated innate and adaptive immune cell activities. Most of the products demonstrated anti-inflammatory properties, except ultrafiltered colostrum, which stimulated the lipopolysaccharide-activated PBMC production of inflammatory cytokines. These products can be potentially used to support overall immune health.

Background

Antisense transcript of the B-cell translocation gene 3 (ASBEL) is a highly conserved antisense non-coding RNA (ncRNA) and participates in a variety of biological processes. However, the ASBEL expression status in pancreatic ductal adenocarcinoma (PDAC) and its correlation with BTG3 expression and tumor cell progression were not completely clear.

Objective

We conducted cell experiments and animal experiments to confirm that ASBEL plays a crucial role in the tumorigenesis of PDAC by targeting BTG3.

Methods

ASBEL regulation in PDAC tumorigenesis was evaluated using Western blotting, quantitative polymerase chain reaction, Cell Counting Kit-8 assay, flow cytometry, and cell transfection. We also evaluated the expression of ASBEL and BTG3 in tumor tissues and cells using Western blotting and quantitative real-time polymerase chain reaction. Finally, we explored the role of ASBEL in tumor development by silencing or overexpressing ASBEL gene in AsPC-1 or CFPAC-1 cells, respectively, and evaluated the antitumor activity in vivo using an ASBEL antagonist.

Results

Our study revealed the expression of ASBEL in all pancreatic cell lines. The expression level of ASBEL in tumor tissues was found to be higher than that of paracarcinomatous tissues. ASBEL suppresses expression of BTG3, enhances proliferation and suppresses apoptosis, and promotes migration and invasion in pancreatic cancer cell. Antagonist regulates the expression of ASBEL in AsPC-1, and suppresses tumor growth in xenograft mouse model.

Conclusions

Our results indicate that ASBEL may play a tumor-promoting factor in PDAC by targeting BTG3 and could be as an important biomarker for PDAC treatment. (Curr Ther Res Clin Exp. 2023; 84:XXX–XXX).