Current Reviews in Clinical and Experimental Pharmacology最新文献

Background: The current therapy of Rheumatoid Arthritis (RA) is confronted with many challenges such as inadequate response, infection, and treatment failure.

Aim and objective: The main objective was to assess the efficacy and safety of tocilizumab (TCZ) in subjects with RA using the available evidence from published randomized controlled trials.

Methods: The current systematic review was performed on nine randomized controlled trials from 2002 to 2016 for TCZ in subjects with rheumatoid arthritis. The primary outcomes were the clinical improvement in American College Rheumatology 20% (ACR20) or Disease Activity Score remission (DAS28), in addition to other outcomes such as ACR50 and ACR70 in the intention-to-treat population.

Results: We have conducted a systematic review on nine randomized controlled trials, with 4129 [100%] enrolled, of which 3248 [78.7%] were on the intention-to-treat. 2147 (66.1%) were treated with TCZ and 1101 (33.9%) have had received placebo or methotrexate or other conventional Disease- Modifying Anti-rheumatic Drugs (cDMARD) or biologic Disease-Modifying Anti-rheumatic Drugs (bDMARDs). In subjects taking TCZ with or without concomitant methotrexate, compared to placebo, subjects treated with TCZ 4 or 8 mg/kg were substantially and statistically significantly more likely than placebo or methotrexate to achieve the ACR20 and/or DAS28. There were no statistically significant differences in serious adverse events such as serious infection; however, subjects on TCZ were more likely to have increased lipid profiles.

Conclusion: TCZ mono-therapy or in combination with methotrexate is valuable in diminishing rheumatoid arthritis disease activity and improving disability. Treatment with TCZ was associated with a significant surge in cholesterol levels but no serious adverse effects. Randomized clinical trials with safety as the primary outcome are warranted to report these safety issues.

The neurobiology drug discovery landscape has transformed over the past decade or so by the discovery of allosteric modulators of receptor superfamilies. A wide range of physiological reactions can occur in response to a limited number of neurotransmitters. This review provides an update on physiological features of the receptors and the signaling pathways that are generated in response to neuroreceptor activation that allow the explanation of this vast array of neurotransmitter responses. Primarily based upon structure, receptors in the nervous system can be classified into four groups: Gprotein coupled receptors, ligand-gated receptors, enzyme-linked receptors, and nuclear receptors. With a particular emphasis on the central nervous system, i.e., brain, spinal cord, and optic nerves, we identify the neuroreceptors, their endogenous agonists, antagonists, sites of expression within the nervous system, current neuropharmacological clinical use, and potential for new drug discovery. New molecular approaches and advances in our knowledge of neuronal communication in processes involved in development, functioning and disorders of the nervous system combined with opportunities to re-purpose existing drugs for new indications continue to highlight the exciting opportunities to improve human health.

Aim: Various research was conducted during the last decade, with inconsistent findings regarding iron death anaemia (IDA) perils vis-à-vis utilization of proton-pump inhibitors (PPIs). Consequently, recent systematic review and meta-analysis were implemented to evaluate IDA-related perils concerning the utilization of proton-pump inhibitors.

Methods: The databases of EBSCOhost, PubMed® and Cochrane Central were searched from the research outset until February 28, 2021 purposely to identify all research with objectives that align with the present research investigation. The Newcastle-Ottawa Scale (NOS) was utilized for the evaluation of the research investigation standard. The prime (1º) goal of the research was to gauge IDA peril among users of proton-pump inhibitors (PPI). For data processing, RevMan (Review Manager) version 5.4 was employed.

Results: In total, fourteen investigations research was employed in this systematic review and metaanalysis. The combined relative risk of nine research exhibited a numerically consequential interrelation betwixt the utilization of proton-pump inhibitors and IDA peril (RR 2.56 [95% CI 1.43-4.61], p < 0.00001). Contemporary systematic review and meta-analysis examination posit that proton-pump inhibitor consumers are prone to greater peril of coming down with IDA in comparison to non-PPI users.

Conclusion: In keeping with the findings of my research, prescriber physicians should exercise caution when prescribing PPIs to individuals taking it for a long time to avoid the peril of IDA. Additionally, their serum iron level should be checked to ensure that proton-pump inhibitors are safe.

Background: H. pylori infection, one of the most prevalent infectious diseases, can cause severe health problems. Therefore, it seems to be crucial to effectively counter the H. pylori infection with a well-tolerated eradication regimen. However, since the discovery of H. pylori, the optimal treatment for this disease is still unclear and remains controversial.

Objectives: The present study aims to estimate the efficacy of standard triple therapy for eradicating H. pylori by systematic review and meta-analysis.

Methods: We identified randomized clinical trials [RCTs] involving triple therapy PPIAC/M [Omeprazole, Amoxicillin, and Clarithromycin/Metronidazole] in the first-line treatment of H. pylori infection and reported eradication rate through electronic and manual searches in PubMed, ISI, EMBASE, the Cochrane Central Register, and Scopus databases. Data were analyzed using the random effect model, and the Cochrane Q test and I² statistics were used to assess heterogeneity. Statistical analyses were performed using STATA version 12.

Results: Forty-seven RCTs [PPIAC: 40 RCTs and PPIAM: 7 RCTs] with 4,938 patients selected as eligible for the final analysis. Per-protocol eradication rate was 80% [95% CI: 74-84] and 80% [95% CI: 73-87] for PPIAC and PPIAM regimens, respectively. The eradication rate for PPIAC and PPIAM regimens was 83% [95% CI: 70%-95%] and 83% [95% CI: 75%-90%] and also 77% [95% CI: 68%- 88%] and 78% [95% CI: 69%-88%], respectively. Based on different treatment durations, the pooled estimates of PP [per-protocol analysis] treatment outcomes were found the highest in 14-day treatment in both regimens.

Conclusion: Standard triple therapy PPIAC/M is recommended to be an effective and safe regimen, although adequate data are not available to suggest PPIAC/M as the first-line therapy for H. Pylori infection. Interestingly, our analysis demonstrated that PPIAC/M regimens were more effective in Asian than European populations.

Background: Disease-Modifying Therapies (DMTs) for Multiple Sclerosis (MS) are widely used given their proven efficacy in the relapsing form of the disease, while recently, Siponimod and Ocrelizumab have been approved for the progressive forms of the disease. Currently, 22 diseasemodifying drugs are approved by the FDA, while in 2012, only nine were present in the market. From March 2019 until August 2020, six new drugs were approved. This rapid development of new DMTs highlighted the need to update our knowledge about their short and long-term safety.

Objective: This review summarizes the available safety data for all the Disease-Modifying Therapies for Multiple Sclerosis and presents the monitoring plan before and during the treatment.

Methods: A literature search was conducted using PUBMED and COCHRANE databases. Key journals and abstracts from major annual meetings of Neurology, references of relevant reviews, and relative articles were also manually searched. We prioritized systematic reviews, large randomized controlled trials (RCTs), prospective cohort studies, and other observational studies. Special attention was paid to guidelines and papers focusing on the safety and monitoring of DMTs.

Conclusion: Data for oral (Sphingosine 1-phosphate (S1P) receptor modulators, Fumarates, Teriflunomide, Cladribine), injectables (Interferons, Glatiramer acetate, Ofatumumab), and infusion therapies (Natalizumab, Ocrelizumab, Alemtuzumab) are presented.

Recent reports suggest that prediabetes is a risk factor for developing severe COVID-19 complications through underlying mechanisms involving undiagnosed sub-clinical inflammation. However, we remain without a clinical approach for managing COVID-19 in prediabetic cases. The subclinical inflammation in prediabetes is associated with elevated DPP4 levels and activity. DPP4 has pleiotropic actions, including glycaemia regulation and immuno-modulation. Recently, DPP4 has been recognised as a co-receptor for COVID-19 for entering host cells. In addition to improving glycaemia, DPP4 inhibition is associated with reduced inflammation. In this submission, we explore the potential use of DPP4 inhibitors as therapeutic agents for prediabetic patients in managing the deleterious effects of COVID-19. DPP4 inhibitors (gliptins), such as linagliptin and sitagliptin, have therapeutic effects, which have been shown to extend beyond glycaemic control with no risk of hypoglycaemia. By the nature of their mechanism of action, gliptins are not associated with hypoglycaemia, unlike their anti-glycaemic counterparts, as they mainly target postprandial glycaemia. Moreover, DPP4 inhibitors may represent a safer option for prediabetic individuals in managing prediabetes either as a prophylactic or curative treatment for COVID-19. We envisage that beyond improved glycaemic control, the use of DPP4 inhibitors would also alleviate the cytokine storm, resulting in a reduction in the severity of COVID-19 symptoms and consequently reducing the morbidity and mortality in prediabetic COVID- 19 patients.

Background: Matrix metalloproteinases, as components of the proteolytic system, are deemed to be implicated in the pathogenesis and progression of several rheumatic diseases. Their role in spondyloarthritis has been investigated by several studies.

Objective: This article aims to review and summarize the current knowledge related to metalloproteinases in patients with spondyloarthritis.

Methods: To examine the association between matrix metalloproteinases and spondyloarthritis, we conducted a narrative review using a literature search in SCOPUS for English-language sources. The search included studies published from the database inception to December 2020.

Results: A total number of 74 articles were included. It was found that levels of matrix metalloproteinases 3 were higher in radiographic axial spondyloarthritis patients and seemed to play a role in the progression of joint damage. The levels of matrix metalloproteinases 1, 2, and 9 were upregulated in psoriatic arthritis patients compared to psoriasis and could identify psoriasis patients who would develop rheumatic manifestations. The levels of matrix metalloproteinases correlated significantly with disease activity in ankylosing spondylitis and decreased upon treatment with Tumor Necrosis Factor inhibitors (TNFi).

Conclusion: Excessive matrix metalloproteinases activity is associated with articular destruction. Their levels can reflect disease activity, structural damage, and response to TNFi in patients with spondyloarthritis. Nevertheless, further studies are needed to confirm these results.

In Covid-19 cases, elderly patients in long-term care facilities, children younger than five years with moderate symptoms, and patients admitted to ICU or with comorbidities are at a high risk of coinfection, as suggested by the evidence. Thus, in these patients, antibiotic therapy based on empirical evidence is necessary. Finding appropriate antimicrobial agents, especially with antiviral and anti-inflammatory properties, is a promising approach to target the virus and its complications, hyper-inflammation, and microorganisms resulting in co-infection. Moreover, indiscriminate use of antibiotics can be accompanied by Clostridioides difficile colitis, the emergence of resistant microorganisms, and adverse drug reactions, particularly kidney damage and QT prolongation. Therefore, rational administration of efficient antibiotics is an important issue. The main objective of the present review is to provide a summary of antibiotics with possible antiviral activity against SARS-CoV-2 and anti-immunomodulatory effects to guide scientists for further research. Besides, the findings can help health professionals in the rational prescription of antibiotics in Covid-19 patients with a high risk of co-infection.

Background: Deficits in cognitive functions are observed in various diseases. The term "nootropics" refers to the compounds that increase mental functions, including memory, motivation, concentration and attention. Given the complexity and vastness of the processes involved in cognition, developing an appropriate animal model for the screening of nootropic agents still remains a daunting task.

Objectives: This review attempts to elicit the current trends in the animal models being used for screening of nootropic agents and effectively use this knowledge to improve prospects embarking on this area of research.

Methods: Electronic searches were carried out on PubMed using the keywords "nootropic agents"[MeSH Term] OR "nootropic drugs" [MeSH Term] AND "animal model" [MeSH Term] OR "animal model, experimental" [MeSH Term]. All relevant studies from 2016 to 31st August, 2021, were then reviewed to meet the stated objective.

Results: The most commonly used disease model for screening of nootropic agents was found to be the animal model of Alzheimer's disease. Disease models of vascular dementia or stroke, depression or anxiety, schizophrenia, epilepsy or seizure, diabetes and traumatic brain injury, among others, have also been used. There exists a wide variety of behavioral tests to assess cognition.

Conclusion: Since a variety of etiologies can affect cognitive processes. Hence, a nootropic agent may be screened in a variety of disease models. The most widely used and appropriate method to assess cognition would be by combining the behavioral and biochemical assays so that a more comprehensive profile of the nootropic effects of a drug can be elicited.