scholarly journals THE ROLE OF IN VIVO MODELS IN PREDICTING TRANSDERMAL PERMEABILITY

2021 ◽  
Vol 91 (1) ◽  
pp. 86-98
Author(s):  
S. S. Malchenkova ◽  
◽  
N. S. Golyak ◽  
V. M. Tsarenkov ◽  
◽  
...  
Keyword(s):  
Structural Features ◽  
World Health ◽  
Laboratory Animals ◽  
Tape Stripping ◽  
In Vivo Models ◽  
Advantages And Disadvantages ◽  
Health Organization ◽  
Transdermal Permeability

The article presents the main types of laboratory animals that are used to study the transdermal permeability of chemical compounds. We described the structural features of epidermis, derma and skin appendages in humans and laboratory animals (small rodents, pigs, monkeys). We also emphasized advantages and disadvantages of various laboratory animals as objects for in vivo transdermal modeling. A method of extrapolation called “The parallelogram method” or «Triple Pack» has been singled out to predict the permeability of the human skin in the presence of experimental data on the permeability of the skin of animals in vivo and humans in vitro. The article describes the experimental design (including preparation of animals, premises and the substance applied) to determine transdermal permeability of substances in vivo under the guidelines of the World Health Organization and the Organization for Economic Cooperation and Development. Tissue microdialysis in volunteers has been identified as the most perfect and safest ways to promptly detect substances in the derma and tape stripping has been made in the cells of the stratum corneum.

scholarly journals Homeopathy and cancer: a literature review

2021 ◽  
Vol 10 (36) ◽  
pp. 145-146
Author(s):  
Marina das Neves Gomes ◽  
Carla Holandino
Keyword(s):  
Literature Review ◽  
Cancer Treatment ◽  
Complementary Therapies ◽  
Adverse Reactions ◽  
The Body ◽  
World Health ◽  
In Vivo Models ◽  
Health Organization

The World Health Organization states that deaths from cancer are increasing reaching an estimated 12 million deaths by 2030 [1]. In Brazil will be about 480,000 new cases by the end of 2011 [2]. For the treatment of cancer conventional therapies are used, such as chemotherapy[3] and radiotherapy [4] which can cause many adverse reactions. Complementary therapies such as homeopathy can be combined to traditional cancer treatment with the aim of minimizing these adverse reactions, relieving the symptoms of the disease itself and its treatment. Other complementary therapies which can aid in cancer treatment are electrotherapy, acupuncture and electroacupuncture, nutritional supplements, probiotics, phytotherapy, among others[5]. The literature shows the homeopathic medicines can be prescribed using the patient’s physical constitution as one strategy to help cancer patients [6-11]. This work aims to compile the literature review done with in vitro and in vivo models describing the mechanisms of action of homeopathic medicines used to treat different kinds of cancer. The research findings showed that homeopathy can help the patient to come to terms with the disease, after cancer diagnosis which often brings with itself denial, fear and a host of psychological disorders that cause an unbalance in the body. In addition, some works done with in vitro and in vivo models have shown that homeopathic medicines can modulate the immune system, activating macrophages and inducing the release of cytokines. These and other effects may help the body to overcome the cancer. The use of homeopathic therapy as complementary to conventional cancer treatment has promising results and should be further investigated.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

scholarly journals Virtual Screening and Statistical Analysis in the Design of New Caffeine Analogues Molecules with Potential Epithelial Anticancer Activity

2018 ◽  
Vol 24 (5) ◽  
pp. 576-594 ◽  
Author(s):  
Josivan da Silva Costa ◽  
Karina da Silva Lopes Costa ◽  
Josiane Viana Cruz ◽  
Ryan da Silva Ramos ◽  
Luciane Barros Silva ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Binding Free Energy ◽  
Inhibitory Effect ◽  
Parametric Models ◽  
World Health ◽  
Pharmacokinetic Properties ◽  
Clinically Significant ◽  
Health Organization

About 132 thousand cases of melanoma (more severe type of skin cancer) were registered in 2014 according to the World Health Organization. This type of cancer significantly affects the quality of life of individuals. Caffeine has shown potential inhibitory effect against epithelial cancer. In this study, it was proposed to obtain new caffeine-based molecules with potential epithelial anticancer activity. For this, a training set of 21 molecules was used for pharmacophore perception procedures. Multiple linear regression analyses were used to propose mono-, bi-, tri-, and tetra-parametric models applied in the prediction of the activity. The generated pharmacophore was used to select 350 molecules available at the ZINCpharmer server, followed by reduction to 24 molecules, after selection using the Tanimoto index, yielding 10 molecules after final selection by predicted activity values > 1.5229. These ten molecules had better pharmacokinetic properties than the other ones used as reference and within the clinically significant limits. Only two molecules show minor hits of toxicity and were submitted to molecular docking procedures, showing BFE (binding free energy) values lower than the reference values. Statistical analyses indicated strong negative correlations between BFE and pharmacophoric properties (high influence on BFE lowering) and practically null correlation between BFE and BBB. The two most promising molecules can be indicated as candidates for further in vitro and in vivo analyzes.

scholarly journals Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021

2021 ◽  
Vol 12 ◽  
Author(s):  
Safaet Alam ◽  
Taslima Binte Kamal ◽  
Md. Moklesur Rahman Sarker ◽  
Jin-Rong Zhou ◽  
S. M. Abdur Rahman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Case Series ◽  
Basic Knowledge ◽  
World Health ◽  
Current Status ◽  
Drug Candidates ◽  
Health Organization ◽  
Meta Analyses

COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.

scholarly journals Accelerated repurposing and drug development of pulmonary hypertension therapies for COVID-19 treatment using an AI-integrated biosimulation platform

2020 ◽  
Author(s):  
Kaushik Chakravarty ◽  
Victor Antontsev ◽  
Aditya Jagarapu ◽  
Yogesh Bundey ◽  
Hypatia Hou ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Renin Angiotensin System ◽  
The United States ◽  
Mechanistic Modeling ◽  
World Health ◽  
Channel Blockers ◽  
Health Organization ◽  
Line Of Therapy

Abstract A World Health Organization-declared pandemic, COVID-19, has affected more than 4 million people worldwide with over 100,000 deaths and growing in the United States. Due to the fast-spreading and multi-targeted nature of the virus, it is clear that drugs and/or vaccines need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically Angiotensin converting enzyme (ACE), and Ca2+ -mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors (e.g. benazepril) and calcium channel blockers (CCB, e.g. amlodipine), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCB and ACEI compounds to tissues implicated in COVID-19 pathogenesis.

scholarly journals Definition and Measurement of Follicle Stimulating Hormone

2000 ◽  
Vol 21 (1) ◽  
pp. 5-22 ◽  
Author(s):  
Matthew P. Rose ◽  
Rose E. Gaines Das ◽  
Adam H. Balen
Keyword(s):  
Single Molecule ◽  
Early Recognition ◽  
Biological Activities ◽  
World Health ◽  
In Vitro Assays ◽  
Assay Method ◽  
Endocrine Activity ◽  
Health Organization

Abstract FSH has a key role in the development and function of the reproductive system and is widely used both diagnostically and therapeutically in developmental and reproductive medicine. The accurate measurement of FSH levels, in patients for diagnosis and monitoring and in therapeutic preparations for clinical use, is essential for safe and successful treatment. Historically, FSH was defined on the basis of classical in vivo endocrine activity, and early therapeutic preparations were calibrated using in vivo bioassays. There was early recognition that reference preparations were required for calibration if the results from different laboratories were to be comparable. In response to the perceived need, the World Health Organization established the first standard for such preparations in 1959. Subsequent developments in biotechnology have led to recognition that there is no single molecule that can be uniquely defined as FSH, and that FSH can induce a range of biological activities. Several highly purified standards for FSH are now available, but discontinuity and heterogeneity of estimates of FSH activity in terms of these standards made using in vitro assays and binding assays have been noted. It is thus essential that any measurement of FSH include specification both of the standard with which the measured FSH is compared and the assay method used for that comparison.

scholarly journals Plasticity of fimbrial genotype and serotype within populations of Bordetella pertussis: analysis by paired flow cytometry and genome sequencing

Microbiology ◽  
2014 ◽  
Vol 160 (9) ◽  
pp. 2030-2044 ◽  
Author(s):  
Thomas E. Vaughan ◽  
Catherine B. Pratt ◽  
Katie Sealey ◽  
Andrew Preston ◽  
Norman K. Fry ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Genome Sequencing ◽  
Bordetella Pertussis ◽  
World Health ◽  
Human Respiratory Tract ◽  
Dna Elements ◽  
Health Organization ◽  
Culture Variability

The fimbriae of Bordetella pertussis are required for colonization of the human respiratory tract. Two serologically distinct fimbrial subunits, Fim2 and Fim3, considered important vaccine components for many years, are included in the Sanofi Pasteur 5-component acellular pertussis vaccine, and the World Health Organization recommends the inclusion of strains expressing both fimbrial serotypes in whole-cell pertussis vaccines. Each of the fimbrial major subunit genes, fim2, fim3, and fimX, has a promoter poly(C) tract upstream of its −10 box. Such monotonic DNA elements are susceptible to changes in length via slipped-strand mispairing in vitro and in vivo, which potentially causes on/off switching of genes at every cell division. Here, we have described intra-culture variability in poly(C) tract lengths and the resulting fimbrial phenotypes in 22 recent UK B. pertussis isolates. Owing to the highly plastic nature of fimbrial promoters, we used the same cultures for both genome sequencing and flow cytometry. Individual cultures of B. pertussis contained multiple fimbrial serotypes and multiple different fimbrial promoter poly(C) tract lengths, which supports earlier serological evidence that B. pertussis expresses both serotypes during infection.

scholarly journals Standards for the assay of Creutzfeldt–Jakob disease specimens

2004 ◽  
Vol 85 (6) ◽  
pp. 1777-1784 ◽  
Author(s):  
P. Minor ◽  
J. Newham ◽  
N. Jones ◽  
C. Bergeron ◽  
L. Gregori ◽  
...  
Keyword(s):  
Collaborative Study ◽  
Sample Volume ◽  
World Health ◽  
Systematic Effect ◽  
The Status ◽  
Jakob Disease ◽  
Health Organization ◽  
Sporadic Cjd

Assays for the agent of Creutzfeldt–Jakob disease (CJD) include measurement of infectivity in different animal systems, such as wild-type or transgenic mice, and detection of PrPSc by different methods and formats. The various assays could be best calibrated against each other by use of uniform readily available materials, and samples of four human brains, two from sporadic CJD patients, one from a variant CJD patient and one from a non-CJD patient, have been prepared as 10 % homogenates dispensed in 2000 vials each for this purpose. Results of in vitro methods, particularly immunoblot assays, were compared in the first collaborative study described here. While dilution end-points varied, the minimum detectable volume was surprisingly uniform for most assays and differences in technical procedure, other than the sample volume tested, had no detectable systematic effect. The two specimens from sporadic CJD cases contained both type 1 and type 2 prion proteins in approximately equal proportions. The materials have been given the status of reference reagents by the World Health Organization and are available for further study and assessment of other in vitro or in vivo assay procedures.

scholarly journals Natural and Synthetic Biomaterials for Engineering Multicellular Tumor Spheroids

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2506
Author(s):  
Advika Kamatar ◽  
Gokhan Gunay ◽  
Handan Acar
Keyword(s):  
Cancer Research ◽  
Three Dimensional ◽  
3D Culture ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
In Vivo Models ◽  
Advantages And Disadvantages ◽  
Natural And Synthetic

The lack of in vitro models that represent the native tumor microenvironment is a significant challenge for cancer research. Two-dimensional (2D) monolayer culture has long been the standard for in vitro cell-based studies. However, differences between 2D culture and the in vivo environment have led to poor translation of cancer research from in vitro to in vivo models, slowing the progress of the field. Recent advances in three-dimensional (3D) culture have improved the ability of in vitro culture to replicate in vivo conditions. Although 3D cultures still cannot achieve the complexity of the in vivo environment, they can still better replicate the cell–cell and cell–matrix interactions of solid tumors. Multicellular tumor spheroids (MCTS) are three-dimensional (3D) clusters of cells with tumor-like features such as oxygen gradients and drug resistance, and represent an important translational tool for cancer research. Accordingly, natural and synthetic polymers, including collagen, hyaluronic acid, Matrigel®, polyethylene glycol (PEG), alginate and chitosan, have been used to form and study MCTS for improved clinical translatability. This review evaluates the current state of biomaterial-based MCTS formation, including advantages and disadvantages of the different biomaterials and their recent applications to the field of cancer research, with a focus on the past five years.

scholarly journals The Potential Anticancer Activity of Phytoconstituents against Gastric Cancer—A Review on In Vitro, In Vivo, and Clinical Studies

2020 ◽  
Vol 21 (21) ◽  
pp. 8307
Author(s):  
Sylwia Nakonieczna ◽  
Aneta Grabarska ◽  
Wirginia Kukula-Koch
Keyword(s):  
Gastric Cancer ◽  
Natural Products ◽  
World Health ◽  
Plant Origin ◽  
Active Metabolites ◽  
Pharmacological Significance ◽  
Health Organization

Gastric cancer belongs to the heterogeneous malignancies and, according to the World Health Organization, it is the fifth most commonly diagnosed cancer in men. The aim of this review is to provide an overview on the role of natural products of plant origin in the therapy of gastric cancer and to present the potentially active metabolites which can be used in the natural therapeutical strategies as the support to the conventional treatment. Many of the naturally spread secondary metabolites have been proved to exhibit chemopreventive properties when tested on the cell lines or in vivo. This manuscript aims to discuss the pharmacological significance of both the total extracts and the single isolated metabolites in the stomach cancer prevention and to focus on their mechanisms of action. A wide variety of plant-derived anticancer metabolites from different groups presented in the manuscript that include polyphenols, terpenes, alkaloids, or sulphur-containing compounds, underlines the multidirectional nature of natural products.

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