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Current Reviews in Clinical and Experimental Pharmacology - Online First
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Bigels as Novel Drug Delivery Systems: A Systematic Review on Efficiency and Influential Factors
Available online: 30 October 2024More LessBackgroundBigles are novel formulation merging two phase of hydrogel and organogel revealing dual properties to release active agents based on their lipophilic or hydrophilic nature.
MethodsA systematic search was conducted in PubMed, Scopus, and ISI Web of Science to find eligible studies evaluating the efficiency of bigels in drug release. 20 articles were included in the analysis based on the defined criteria.
ResultsThe results indicated that several different natural materials were used for bigel making. Span (52.38%) and Sunflower oil (23.80%) were the most solvents used for organogel formation. Also, gelatin, agar, gums, and other types of biopolymer were used as hydroglators. Most research (33.33%) focused on the release of metronidazole from bigel structure. Also, the range of drug release rates was 1.59 - 100% and in 42.85% of studies was >90%. The nature, content, and properties of both organogel and hydrogel and some process variables such as temperature, mixing speed and storage conditions were highlighted as the main influential factors on bigel formation and its bioactivity.
ConclusionBigels are an innovative structure that provides desired physicochemical and rheological properties for industrial applications. Excellent biocompatibility and in vitro / ex vivo results have been documented for developed bigels. In this regard, an optimal preparation method is very important to show superior therapeutic effects.
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Effectiveness and Tolerability of Various 5-Fluorouracil Formulations as Adjuvant Therapies for Vitiligo Management: A Systematic Review and Meta-Analysis
Authors: Neveen A. Kohaf, Sameh M. Sarsik, Samar Salman and Omnya M. AminAvailable online: 18 October 2024More LessBackgroundAll vitiligo treatments are restricted, and no known treatment reliably produces repigmentation. In this study, we investigated the efficacy and safety of 5-Fluorouracil (5FU) as adjuvant therapy in treating vitiligo.
MethodUsing five significant databases, an electronic systematic search of the literature was conducted. Randomized Clinical Trials (RCTs) that investigated 5FU for treating vitiligo in humans were selected for a meta-analysis and systematic review. This study was conducted by following PROSPERO (CRD42022345736).
ResultsA total of 10 studies involving 302 patients were included in our systematic review. The meta-analysis of eight studies revealed that the combination of 5FU with microneedling showed a statistically significant superior effect in comparison with other treatment modalities in inducing >75% repigmentation (OR= 4.47; 95%CI= (2.39, 8.35), P < 0.00001). 5FU with microneedling versus microneedling alone showed higher efficacy of 5FU with statistically significant results (OR= 4.22; 95%CI= (1.55, 11.44), P= 0.005). Regarding the influence of different formulations of 5FU, the meta-regression revealed that the highest efficacy was achieved when microneedling was combined with liposomal formulations. There were not any reported severe side effects related to 5FU.
Conclusion5FU as an adjuvant treatment for vitiligo was found to be more effective in achieving ≥75% repigmentation rates.
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Understanding Diabetic Wounds: A Review of Mechanisms, Pathophysiology, and Multimodal Management Strategies
Authors: Manisha, Niharika, Praveen Gaur, Radha Goel, Kanak Lata and Rosaline MishraAvailable online: 14 October 2024More LessIntroductionDiabetic wounds are a prevalent and impairing consequence of diabetes mellitus that significantly impacts people's lives and global healthcare systems. Because of disturbances in the wound-healing cascade, these intricate, persistent wounds frequently refuse to heal. Focusing on diabetic wound formation, this study seeks to clarify the complex mechanisms and pathophysiology involved while offering a thorough overview of modern multimodal therapy techniques. The etiology of diabetic wounds entails a complex interplay between tissue destruction caused by hyperglycemia, neuropathy, ischemia, and compromised immune response. Extended inflammation, abnormal protease activity, and low oxygen levels in the tissue exacerbate the healing process. Comprehending these pathogenic mechanisms is essential for formulating efficacious therapeutic strategies.
MethodologyA thorough evaluation of the literature was done. Databases like SciFinder, ScienceDirect, PubMed, Google, Google Scholar, and the Egyptian Knowledge Bank were used to find pertinent publications. More than 200 articles and databases were studied to constitute this paper. The accuracy of the retrieved data was carefully reviewed and cross-checked. The current review aims to define wounds, various methods of classification, and various advancements for wound management as mentioned in scheme 1. Several multidisciplinary strategies, including debridement, unloading, antimicrobial stewardship, and innovative therapeutics, are currently needed to manage diabetic wounds. Debridement—the excision of non-viable tissue—is necessary to create an environment that is conducive to recovery. Biomechanical interventions and offloading help to prevent additional tissue damage caused by repetitive stress. Antimicrobial treatments fight infections, which are a common diabetic wound consequence. Promising supplementary treatments are provided by developments in cellular and tissue-based products, ozone therapy growth factors, bioengineered skin substitutes, and hyperbaric oxygen therapy.
ResultAfter applying article selection criteria and reviewing the quality of the methodology a total of 200 articles were selected to be included in the review. In this review, intricate interactions between peripheral neuropathy, vascular insufficiency, and hyperglycemia in the pathophysiology of diabetic wounds are explained. The efficacy of multimodal therapies is discussed in detail.
DiscussionA thorough comprehension of the complex mechanisms that underlie diabetic wounds is essential for efficient therapy. This review emphasizes how important multimodal approaches are to treating the complex pathophysiology of these wounds. Clinicians can greatly enhance the prognosis of patients with diabetic foot ulcers by addressing vascular insufficiency, neuropathy, infection, and poor healing.
ConclusionTimely wound resolution remains a key difficulty despite the implementation of multimodal methods. To customize therapies, personalized medicine strategies utilizing genetic and proteomic biomarkers must be the main focus of future research. Furthermore, cutting-edge biotechnologies with the potential to transform diabetic wound treatment include optogenetics and nanomedicine.
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Bleeding vs Thrombosis: Treatment Strategy for Women Having Large Uterine Fibroids and DVT
By Kiran SharmaAvailable online: 09 October 2024More LessLarge uterine fibroids (UFs) are clonal neoplasms of the uterus that form during the mid and late-aged women. Such women generally consume oral contraceptive pills, tranexamic acid, or NSAIDS to manage heavy menstrual bleeding (HMB) and associated complications while waiting for a conclusive procedure or avoiding hysterectomy. The procoagulant effect of these medicinal agents can result in venous stasis of the lower limbs, leading to deep vein thrombosis (DVT), a challenging complication with HMB. We examine the complicated state of heavy bleeding with thrombosis and explore better management options. It has been seen that women with hypothyroidism have an increased risk of getting DVT due to an alteration in the coagulation system. These incidences are mostly associated with higher uterine weight, which is related to the extrinsic compression of the inferior vena cava. In such cases, the occurrence of postoperative thrombosis is riskier if hysterectomy/myomectomy is the only option. Utilization of appropriate anticoagulants with modification of the steroid-hormone system using hormone agonists or antagonists (e.g., levonorgestrel intrauterine system, high-dose progestin-only therapy, danazol, aromatase inhibitors, Vitamin-D supplements or selective estrogen receptor modulators) could be an effective technique, but adverse consequences of continued use should be monitored. More research is needed into the basic biology associated with the role of growth factors and genetic alterations in these malignancies. The development of new leiomyomas following conservative therapy is also a significant issue.
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Interferon Causes Endothelial Injury in Humans
Available online: 07 October 2024More LessTherapy with exogenous interferon and human conditions that feature endogenous interferon upregulation may be associated with endothelial damage that primarily involves small blood vessels. Endothelial injury associated with interferon may display different clinical expression, including thrombotic microangiopathy, Raynaud’s phenomenon, vasculopathy of dermatomyositis and atrophic papulosis, interferon-associated skin angiopathy, systemic capillary leak syndrome, collapsing glomerulopathy, interstitial lung disease, pulmonary hypertension, and retinopathy. Interferon-induced endothelial damage involves complement-mediated injury, although pathogenic mechanisms by which interferon promote abnormal complement activation on endothelial cells are not fully understood. Human interferon-γ (type II interferon) binds to heparan sulfate on the endothelial surface, suggesting that overproduction of interferon-γ may hinder factor H attachment to the same location. Absence of factor H on self surfaces promotes activation of the alternative pathway of complement and complement-mediated endothelial damage. Type I interferon typically induces the generation of antibodies. Type I interferon upregulation may elicit the formation of autoantibodies against factor H. These autoantibodies block factor H binding to endothelial surfaces, abolishing the protective effect of factor H on complement-mediated damage. In addition, interferon induces insulin resistance which is associated with reduced heparan sulfate in the extracellular matrix, including the endothelial surface. Decreased amount of heparan sulfate suppresses factor H attachment, promoting activation of the alternative pathway of complement. Complement blockade with eculizumab (a monoclonal antibody against C5) improves endothelial damage in patients with thrombotic microangiopathy and other situations associated with interferon upregulation and interferon-induced endothelial injury, suggesting that complement-mediated injury is clinically relevant under conditions that feature interferon overproduction.
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Nonopioid Drugs for Postoperative Pain: A Selection Governed by Choices of the Authors of Academic Articles
Authors: Igor Kissin and Kamen V. VlassakovAvailable online: 01 October 2024More LessThe opioid crisis has profoundly changed the interest in using nonopioid analgesics. This review identified nonopioid drugs receiving the most interest in the treatment of postoperative pain. Publication-based interest, which reflects the authors’ choices of subjects for academic articles, was used to show the shifts in their interest. The authors’ choices of a particular drug for an article’s subject were regarded as reflective of the collective opinion of experts most knowledgeable on the subject. The frequency with which a drug was the topic of an article was measured with the use of specific bibliometric indices. They were employed to select nonopioid drugs for this review. These included acetaminophen, dexmedetomidine, dexamethasone, ketamine, gabapentin, ibuprofen, ketorolac, diclofenac, magnesium sulfate, clonidine, intravenous lidocaine, and meloxicam (in order of most to least bibliometric interest). Individual reviews on these agents described how the bibliometric indices characterized a drug. They also addressed the question of whether a nonopioid analgesic produced a marked opioid-sparing effect. Information relative to this question was presented via the results of meta-analyses with emphasis on the possible reduction of opioid-related side effects. Overall, nonopioid drugs demonstrating the largest popularity among authors and continuous interest growth in 2018-2022 include acetaminophen, dexmedetomidine, dexamethasone, and ibuprofen. The relevant meta-analyses show that nonopioids, administered as components of multimodal analgesia, provided the opioid-sparing effect; they also show that the most common change in the opioid-related side effects was a lower incidence of postoperative nausea and vomiting.
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