scholarly journals Managing Skin Ageing as a Modifiable Disorder – The Clinical Application of Nourella® Dual Approach Comprising a Nano-encapsulated Retinoid, Retilex-A® and a Skin Proteoglycan Replacement Therapy, Vercilex®

2021 ◽  
Author(s):  
Jan Wadstein ◽  
Israel Sánchez Alvarez ◽  
Erling Thom ◽  
Lidia Bernal López
Keyword(s):  
Replacement Therapy ◽  
Skin Irritation ◽  
Dual Therapy ◽  
Skin Thickness ◽  
Synergistic Activity ◽  
Therapeutic Modalities ◽  
Photoaged Skin ◽  
Topical Retinoids ◽  
Wide Range ◽  
Aged Skin

Skin ageing is a progressive but modifiable, multi-factorial disorder that involves all skin tissues. Pertaining to its wide range of physiological and psychosocial complications, skin ageing requires rigorous clinical attention. Topical retinoids and per-oral proteoglycans are promising, non-invasive, therapeutic modalities. To overcome the low bioavailability of conventional free retinoids, Nourella® cream with Retilex-A® (Pharma Medico, Aarhus, Denmark) was developed using a proprietary nano-encapsulation technology. The nano-encapsulation is a sophisticated ‘permeation/penetration enhancer’ that optimises topical drug delivery by increasing surface availability and net absorption ratio. Treatment adherence is also improved by minimising skin irritation. Interventional evidence supports the higher efficacy of Retilex-A® in improving skin thickness and elasticity compared with conventional free forms. It is also reported that the rejuvenating efficacy of Retilex-A® and tretinoin are comparable. Another skin anti-ageing approach is proteoglycan replacement therapy (PRT) with Vercilex®. Vercilex® in Nourella® tablet has the potential to ameliorate proteoglycan dysmetabolism in the aged skin by activating skin cells and improving collagen/elastin turnover. Replicated clinical trials evidenced that PRT can significantly enhance the density, elasticity and thickness of both intrinsically aged and photoaged skin. Evidently, Vercilex® and Retilex-A® share a range of bioactivities, which underlies their synergistic activity observed in a clinical trial. Dual therapy with Nourella® tablets and cream produced higher effect sizes on skin characteristics than monotherapy with each of the two treatments. In conclusion, Nourella® cream and tablets are safe and effective treatments for skin ageing; however, combining the two in a ‘dual skin rejuvenation system’ significantly improves treatment outcomes.

The Management of Post-Tonsillectomy Morbidity in Patients With Sleep Apnoea

2019 ◽  
Vol 70 (10) ◽  
pp. 3738-3740
Keyword(s):  
Day Surgery ◽  
Sleep Apnoea ◽  
Integrative Approach ◽  
Multicenter Studies ◽  
Therapeutic Modalities ◽  
Advantages And Disadvantages ◽  
Obstructive Sleep ◽  
Wide Range ◽  
The Impact ◽  
Surgery Center

The Tonsillectomy in children or adults is an intervention commonly encountered in the ENT (Ear Nose and Throat) and Head and Neck surgeon practice. The current tendency is to perform this type of surgery in major ambulatory surgery centers. Two objectives are thus pursued: first of all, the increase of the patient quality of life through the reintegration into the family as quickly as possible and secondly, the expenses associated with continuous hospitalization are reduced. Any tertiary (multidisciplinary) sleep center must ensure the complete diagnosis and treatment (including surgery) of sleep respiratory disorders. Under these conditions the selection of patients and especially the implementation of the specific protocols in order to control the postoperative complications it becomes essential. The present paper describes our experience of tonsillectomy as treatment for selected patients with chronic rhonchopathy (snoring) and mild to moderate obstructive sleep apnoea. It was presented the impact of antibiotics protocols in reducing the main morbid outcomes following tonsillectomy, in our day surgery center. The obtained results can also be a prerequisite for the integrative approach of the patients with sleep apnoea who were recommended surgical treatment. Considering the wide range of therapeutic modalities used in sleep apnoea, each with its specific advantages and disadvantages, more extensive and multicenter studies are needed. Keywords: post-tonsillectomy morbidity, day surgery center, sleep disorders

Application of essential oils as natural cosmetic preservatives

2013 ◽  
Vol 59 (4) ◽  
pp. 142-156 ◽  
Author(s):  
Mariola Dreger ◽  
Karolina Wielgus
Keyword(s):  
Essential Oil ◽  
Essential Oils ◽  
Contact Allergy ◽  
Skin Irritation ◽  
Antimicrobial Properties ◽  
Antimicrobial Effect ◽  
Synergistic Activity ◽  
Minimum Concentration ◽  
Current State ◽  
Risk Benefit Assessment

Abstract Nowadays, safety of chemical preservatives has been questioned by a big number of consumers. Traditionally used preservatives often cause skin irritation and lead to allergenic reactions. Growing demands for more natural and preservative-free cosmetics promoted an idea of the replacement of synthetic preservatives with essential oils (EOs) of antimicrobial properties. The antimicrobial effect of essential oil depends on content, concentration and interactions between the main active compounds. Effective preservatives should be characterized by a broad spectrum of antimicrobial activity at a minimum concentration. Formulations containing both types of preservatives: essential oil and a synthetic one have been tested and proposed as a compromise that allows for reducing concentration of both components due to their synergistic activity. Although most essential oils are regarded as safe, some of them may cause risk of contact allergy or phototoxic reaction. A well balanced risk-benefit assessment of essential oils is one of the great challenges for scientists or health policy authorities. This paper presents current state of knowledge on essential oils focused on their antimicrobial properties, the assessment of their efficacy and safety as cosmetic preservatives.

scholarly journals A network-oriented perspective on cardiac calcium signaling

2012 ◽  
Vol 303 (9) ◽  
pp. C897-C910 ◽  
Author(s):  
Christopher H. George ◽  
Dimitris Parthimos ◽  
Nicole C. Silvester
Keyword(s):  
Network Architecture ◽  
Dynamic Range ◽  
Chaotic Behavior ◽  
Dynamic Network ◽  
Signaling Network ◽  
Therapeutic Modalities ◽  
Cell Network ◽  
Biological Oscillators ◽  
Wide Range ◽  
Cellular Ca

The normal contractile, electrical, and energetic function of the heart depends on the synchronization of biological oscillators and signal integrators that make up cellular signaling networks. In this review we interpret experimental data from molecular, cellular, and transgenic models of cardiac signaling behavior in the context of established concepts in cell network architecture and organization. Focusing on the cellular Ca2+ handling machinery, we describe how the plasticity and adaptability of normal Ca2+ signaling is dependent on dynamic network configurations that operate across a wide range of functional states. We consider how (mal)adaptive changes in signaling pathways restrict the dynamic range of the network such that it cannot respond appropriately to physiologic stimuli or perturbation. Based on these concepts, a model is proposed in which pathologic abnormalities in cardiac rhythm and contractility (e.g., arrhythmias and heart failure) arise as a consequence of progressive desynchronization and reduction in the dynamic range of the Ca2+ signaling network. We discuss how a systems-level understanding of the network organization, cellular noise, and chaotic behavior may inform the design of new therapeutic modalities that prevent or reverse the disease-linked unraveling of the Ca2+ signaling network.

scholarly journals Phase-Separating Peptides for Direct Cytosolic Delivery and Redox-Activated Release of Macromolecular Therapeutics.

2021 ◽  
Author(s):  
Yue Sun ◽  
Sze Yi Lau ◽  
Zhi Wei Lim ◽  
Shi Chieh Chang ◽  
Farid Ghadessy ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Transfection Efficiency ◽  
Cellular Membrane ◽  
Small Peptides ◽  
Therapeutic Modalities ◽  
Cytosolic Delivery ◽  
Wide Range ◽  
Redox Responsive ◽  
Intracellular Targets ◽  
Liquid Liquid Phase Separation

Abstract Biomacromolecules are highly promising therapeutic modalities to treat various diseases. However, they suffer from poor cellular membrane permeability, limiting their access to intracellular targets. Strategies to overcome this challenge employ nanoscale carriers that often get trapped in endosome compartments. Here, we report on conjugated peptides forming pH- and redox-responsive coacervate microdroplets by liquid-liquid phase separation (LLPS) that readily cross the cell membrane. A wide range of macromolecules can be quickly recruited within the microdroplets, from small peptides to enzymes as large as 430 kDa to mRNAs. The therapeutic-loaded coacervates bypass endocytosis to directly enter in the cytosol, where they undergo glutathione-mediated release of payload whose bioactivity is retained in the cell, whereas mRNAs exhibit a high transfection efficiency. These peptide coacervates represent a promising platform for intracellular delivery of a large palette of macromolecular therapeutics that have potential in the treatment of various pathologies (e.g. cancers and metabolic diseases), or as carriers for mRNA-based vaccines.

scholarly journals Formulation and Characterization of Glucosamine Sulphate Loaded Carbopol Based Hydrogels for the Management of Osteoarthritis

2020 ◽  
Vol 11 (4) ◽  
pp. 7121-7127
Author(s):  
Sundareswara Kumar Chellaswamy ◽  
Satheesh Babu Natrajan
Keyword(s):  
Skin Irritation ◽  
Glucosamine Sulfate ◽  
Effective Dosage ◽  
Permeation Enhancers ◽  
Simple Method ◽  
Wide Range ◽  
Glucosamine Sulphate ◽  
Tween 40

Osteoarthritis is emerging as the most ordinary form of arthritis, affecting 22-39% of the Indian population. A wide range of medications and therapies are available for the treatment of osteoarthritis. With a desire to develop a therapeutically effective dosage form, the present study was carried out to formulate glucosamine sulfate loaded carbopol based hydrogel. Hydrogels H1 to H6 were formulated without permeation enhancers while formulations H7 to H12 were developed with a different class of permeation enhancers such as PEG400, oleic acid, Tween 40, DMSO and PG. Based on viscosity, it was detected that formulation H4 containing polymer 1% was ideal for incorporating drug. Considering H4 as a placebo, H6 was used for further evaluation. Drug content was found to be 99.2±0.64, with in vitro  drug release of 15±0.86, 22±1.59, 28±0.72, 35±0.68, 40±0.31, 47±0.83, 58±1.59, and 70±0.9 % at a duration of 1, 2, 3, 4, 5, 6, 7, 8 hours respectively. Skin irritation tests carried out on Wistar rats revealed that skin was intact with no inflammation or erythema detected, compared to untreated site. By diffusion disc method, it was evident that the levels of microbial load were relatively low, and no harmful microorganisms were identified. There were no significant changes in physicochemical properties on stability studies. Due to a simple method of preparation and effective drug delivery, glucosamine sulfate loaded hydrogels could be contemplated as a prominent formulation in the beneficiary treatment of osteoarthritis.

scholarly journals Differentiated approach to replacement therapy in exocrine pancreatic insufficiency

2020 ◽  
Vol 47 (2) ◽  
pp. 37-49
Author(s):  
N. B. Gubergrits ◽  
N. V. Byelyayeva ◽  
A.Ye. Klochkov ◽  
G. M. Lukashevich ◽  
P. G. Fomenko
Keyword(s):  
Replacement Therapy ◽  
Pancreatic Insufficiency ◽  
Skin Irritation ◽  
Exocrine Pancreatic Insufficiency ◽  
Severe Exacerbation ◽  
Enzyme Preparations ◽  
Enzyme Replacement ◽  
Malabsorption Syndromes ◽  
Unpleasant Odor ◽  
Bladder Diseases

The article is an overview of current ideas about indications and features of various enzyme preparations (EP). The following requirements are applied for all EP: nontoxicity, resistance to hydrochloric acid and pepsin, good tolerance by patients, no significant side effects, optimal effect at pH≈6.0, rapid release of enzymatic activity in the small intestine at pH≈6.0, while maintaining this activity no less than 2 hours, high enzyme activity, compliance with the composition stated on the label, high serial homogeneity of the preparation, no unpleasant odor and taste. Considering the variety of pathogenetic mechanisms and nosological units that occur with maldigestion and malabsorption syndromes, the spectrum of indications for EP is rather wide: pancreatic, liver, gall bladder diseases, preparation for instrumental studies, etc. The authors present a modern algorithm (“steps”) of enzyme therapy. A differentiated approach to the choice of EP is developed depending on the pathology that the patient suffers from, EP composition, and features of its action. Attention is drawn to the possible reasons for the lack of effectiveness of replacement therapy, general contraindications to the prescription of EP (acute pancreatitis, severe exacerbation of chronic pancreatitis, hypersensitivity to the drug components) and their individual components (bile acids, nicotinamide, activated charcoal). Complications of enzyme replacement therapy are indicated, namely: pain in the oral cavity; skin irritation in the perianal region; abdominal discomfort; nausea; fibrosing colopathy; allergic reactions; sometimes hyperuricosuria; pancreatin shaping complexes with folic acid, disrupting its absorption.

scholarly journals New Insights Into the Antibacterial Mechanism of Cryptotanshinone, a Representative Diterpenoid Quinone From Salvia miltiorrhiza Bunge

2021 ◽  
Vol 12 ◽  
Author(s):  
Bo-Chen Chen ◽  
Zhi-Shan Ding ◽  
Jian-Sheng Dai ◽  
Ni-Pi Chen ◽  
Xing-Wen Gong ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Antimicrobial Agents ◽  
Salvia Miltiorrhiza ◽  
Membrane Vesicles ◽  
Redox Balance ◽  
Docking Study ◽  
Synergistic Activity ◽  
Metabolome Analysis ◽  
Molecular Docking Study ◽  
Wide Range

The rapid rise of antibiotic resistance causes an urgent need for new antimicrobial agents with unique and different mechanisms of action. The respiratory chain is one such target involved in the redox balance and energy metabolism. As a natural quinone compound isolated from the root of Salvia miltiorrhiza Bunge, cryptotanshinone (CT) has been previously demonstrated against a wide range of Gram-positive bacteria including multidrug-resistant pathogens. Although superoxide radicals induced by CT are proposed to play an important role in the antibacterial effect of this agent, its mechanism of action is still unclear. In this study, we have shown that CT is a bacteriostatic agent rather than a bactericidal agent. Metabolome analysis suggested that CT might act as an antibacterial agent targeting the cell membrane. CT did not cause severe damage to the bacterial membrane but rapidly dissipated membrane potential, implying that this compound could be a respiratory chain inhibitor. Oxygen consumption analysis in staphylococcal membrane vesicles implied that CT acted as respiratory chain inhibitor probably by targeting type II NADH:quinone dehydrogenase (NDH-2). Molecular docking study suggested that the compound would competitively inhibit the binding of quinone to NDH-2. Consistent with the hypothesis, the antimicrobial activity of CT was blocked by menaquinone, and the combination of CT with thioridazine but not 2-n-heptyl-4-hydroxyquinoline-N-oxide exerted synergistic activity against Staphylococcus aureus. Additionally, combinations of CT with other inhibitors targeting different components of the bacterial respiratory chain exhibit potent synergistic activities against S. aureus, suggesting a promising role in combination therapies.

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