EFFICACY OF ACNE THERAPY IN PATIENTS WITH OVARIAN HYPERANDROGENISM

2021 ◽  
pp. 35-42
Author(s):  
Kalinkina O.B. ◽  
Tezikov Yu.V. ◽  
Lipatov I.S. ◽  
Aravina O.R.
Keyword(s):  
Active Form ◽  
Local Treatment ◽  
The Body ◽  
Favorable Effect ◽  
Dermatological Examination ◽  
Gynecological Examination ◽  
First Choice ◽  
Complex Therapy ◽  
Acne Therapy ◽  
Ovarian Hyperandrogenism

The aim of the study was to show the effectiveness of treatment of acne with moderate severity in women with ovarian hyperandrogenism. A total of 25 female reproductive voerast patients with moderate acne and ovarian hyperandrogenism who were not planning pregnancy were examined. All patients were examined, which included a consultation with a gynecologist with a gynecological examination, ultrasound examination of the pelvic organs, a study of the hormonal status, a biochemical blood test, as well as a dermatological examination with the determination of the dermatological index of acne (DIA). After the examination, the patients underwent complex therapy using the external treatment recommended by the dermatovenerologist (skin cleansing, gel with azelaic acid and / or gel with adapalene), as well as the appointment of a combined oral contraceptive (COC) Jes Plus. Based on this study, it can be concluded that complex therapy, including local treatment and taking Jes Plus, is the first choice in the treatment of androgen-dependent dermopathy, manifested by moderate acne, in patients with ovarian hyperandrogenism due to PCOS. Such therapy contributes not only to the formation of a pronounced clinical result, but also causes a low probability of side effects. The administration of COC containing drospirenon and the active form of folate, in the form of the calcium salt levomefolate, allows a favorable effect on the metabolic processes in the body as a whole, and in particular, provides a positive effect on the skin, the cardiovascular system, reduces the risk of systemic and local inflammation, relieving the state of hyperhomocysteinemia, providing prevention of cardiometabolic risks.

scholarly journals Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Alena Pecinova ◽  
Zdenek Drahota ◽  
Jana Kovalcikova ◽  
Nikola Kovarova ◽  
Petr Pecina ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Respiratory Chain ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Epidemiological Studies ◽  
The Body ◽  
Oxygen Species ◽  
Brown Adipose ◽  
First Choice ◽  
Species Production

Metformin is widely prescribed as a first-choice antihyperglycemic drug for treatment of type 2 diabetes mellitus, and recent epidemiological studies showed its utility also in cancer therapy. Although it is in use since the 1970s, its molecular target, either for antihyperglycemic or antineoplastic action, remains elusive. However, the body of the research on metformin effect oscillates around mitochondrial metabolism, including the function of oxidative phosphorylation (OXPHOS) apparatus. In this study, we focused on direct inhibitory mechanism of biguanides (metformin and phenformin) on OXPHOS complexes and its functional impact, using the model of isolated brown adipose tissue mitochondria. We demonstrate that biguanides nonspecifically target the activities of all respiratory chain dehydrogenases (mitochondrial NADH, succinate, and glycerophosphate dehydrogenases), but only at very high concentrations (10−2–10−1 M) that highly exceed cellular concentrations observed during the treatment. In addition, these concentrations of biguanides also trigger burst of reactive oxygen species production which, in combination with pleiotropic OXPHOS inhibition, can be toxic for the organism. We conclude that the beneficial effect of biguanides should probably be associated with subtler mechanism, different from the generalized inhibition of the respiratory chain.

Optimization of the Global Static and Dynamic Performance of a Vehicle Body by Means of Response Surface Models

2012 ◽  
Author(s):  
Pavlina Mihaylova ◽  
Alessandro Pratellesi ◽  
Niccolò Baldanzini ◽  
Marco Pierini
Keyword(s):  
Response Surface ◽  
Dynamic Performance ◽  
The Body ◽  
Vehicle Body ◽  
Fe Model ◽  
Structural Modifications ◽  
Response Surface Models ◽  
First Choice ◽  
Surface Models ◽  
Body In White

Concept FE models of the vehicle structure are often used to optimize it in terms of static and dynamic stiffness, as they are parametric and computationally inexpensive. On the other hand they introduce modeling errors with respect to their detailed FE equivalents due to the simplifications made. Even worse, the link between the concept and the detailed FE model can be sometimes lost after optimization. The aim of this paper is to present and validate an alternative optimization approach that uses the detailed FE model of the vehicle body-in-white instead of its concept representation. Structural modifications of this model were applied in two different ways — by local joint modifications and by using mesh morphing techniques. The first choice was motivated by the strong influence of the structural joints on the global vehicle performance. For this type of modification the plate thicknesses of the most influent car body joints were changed. In the second case the overall car dimensions were modified. The drawback of using detailed FE models of the vehicle body is that they can be times bigger than their concept counterparts and can thus require considerably more time for structural analysis. To make the approach proposed in this work a feasible alternative for optimization in the concept phase response surface models were introduced. With them the global static and dynamic performance of the body-in-white was represented by means of approximating polynomials. Optimization on such mathematical models is fast, so the choice of the optimization algorithm is not limited only among local-search strategies. In the current study Genetic Algorithm was used to increase the chances for finding better design alternatives. Two different optimization problems were defined and solved. Their final solutions were presented and compared in terms of structural modifications and resulting responses. The approach in this paper can be successfully used in the concept phase as it is fast and reliable and at the same time it avoids the problems typical for concept models.

scholarly journals Design and Synthesis of Antiviral Iminoribitol C-Nucleosides

2021 ◽  
Author(s):  
◽  
Ye Li
Keyword(s):  
Antiviral Activity ◽  
Rna Polymerase ◽  
Nucleoside Analogue ◽  
Rna Viruses ◽  
Active Form ◽  
Building Blocks ◽  
The Body ◽  
Nucleoside Analogues ◽  
Federal Drug Administration ◽  
Pharmacologically Active

<p>Infections caused by RNA viruses, such as Ebola and Zika, continue to exist worldwide as significant public health problems. In response to the urgent need for safer and more efficacious treatment options to treat infections caused by RNA viruses, the pharmaceutical and biotechnology industries have devoted significant efforts over the last two decades to discovering and developing new antiviral agents. One such antiviral, Sofosbuvir®, was approved by the US Federal Drug Administration (FDA) in 2014 and has revolutionized the treatment of Hepatitis-C. Sofosbuvir® was the second largest selling drug in the world in 2016 and in just twenty-one months Gilead reported sales worth $26.6 billion USD.The strategy of using nucleoside analogues to inhibit viral RNA dependent RNA polymerase(RdRp)has been pursued since the 1970s, and exemplified bythe discovery and development of ribavirin. The natural substrates of RNA polymerases are nucleoside triphosphates and often the efficacy of nucleoside analogues as antivirals are dependent on their ability to be converted by the host or virus to mono-, di-, and ultimately tri-phosphate analogues which block the active site of RNA polymerase as an analogue of the substrate causing chain termination. Recently Biocryst Pharmaceuticals (Biocryst) described the anti-viral properties of Immucillin-A (Galidesivir), an iminoribitol based nucleoside analogue, which was found to have broad spectrum antiviral activity especially against RNA viruses including Ebola. Researchers at the Ferrier Research Institute (Ferrier) have synthesizedan analogue of Immucillin-A, 8-aza-Immucillin-A (AIA) which shows comparable activityto Immucillin-A, in anti-viral screens against Ebola, and this antiviral activity forms part of a US patent application. The Ferrier is keen to further exemplify this compound class through the synthesis of analogues of both Immucillin-A and AIA as well as improve the overall synthesis of the lead compound AIA.Included as part of this study is the synthesis of pro-drugs of these iminoribitol based nucleoside analogues. Prodrugs are metabolized inside the body and are often converted to the corresponding pharmacologically active form. In general, prodrug strategies have improved the bioavailability and efficacy of many drugs. In particular, prodrugs strategies involving nucleoside analogue antivirals, which target RNA polymerase, have been particularly effective as they ensure conversion to the monophosphate in vivo. Conversion to the 5’-monophosphate form of a nucleoside analogue is the rate limiting step to the inhibition of the RNA polymerase –prior to its conversion to the triphosphateanalogue. The prodrug is effectively a protected monophosphate, and is then readily converted to monophosphate by the host and then onto the di-and tri-phosphate by kinases in both the host and virus. ProTide prodrugs, such as Sofosbuvir® provide a verified strategy for improving anti-viral activity and hence our desire to synthesize pro-drugs of all our iminoribitol based nucleoside analogues. This research thesis also involved repeating the known synthesis of the Immucillins, in particular, Immucillin-H (Forodesine), which requires in excess of 20 linear synthetic steps to make. The linear synthetic route to Immucillin-H was used instead of the more convenient convergent method developed by the Ferrier as several key synthetic intermediates in this progress were utilized in the attempted synthesis of some of the planned nucleoside analogues of AIA. As part of this work the candidate learned aspects of scaling up chemical reactions andthe critical analysis of both reaction hazards and reagent compatibilities at scale. Where possible and given the number of synthetic steps involved the candidate was also interested in improving the yields of the building blocks involved in the synthesis of the Immucillins with limited success.</p>

scholarly journals A relapse of pemphigus vulgaris in pemphigus herpetiformis or a phenotypic “switch”

2022 ◽  
Vol 13 (1) ◽  
pp. 107-108
Author(s):  
Siham Belmourida ◽  
Meriame Meziane ◽  
Nadia Ismaili ◽  
Laila Benzekri ◽  
Badreddine Hassam ◽  
...  
Keyword(s):  
Corticosteroid Therapy ◽  
Transition Period ◽  
Pemphigus Vulgaris ◽  
Skin Lesions ◽  
Exceptional Case ◽  
The Body ◽  
Direct Immunofluorescence ◽  
Phenotypic Switch ◽  
Dermatological Examination ◽  
Phenotypic Transition

Sir, Pemphigus herpetiformis (PH) was originally described by Jablonska et al. in 1975. Clinically, PH presents itself as a herpetiform dermatitis with immunopathological characteristics of pemphigus [1,2]. We report an exceptional case of typical pemphigus vulgaris (PV) relapsing after 36 years in PH. A 65-year-old patient, followed for PV for 36 years and treated with corticosteroid therapy with a remission for more than thirty years, consulted for pruriginous lesions evolving for the previous eight months. A dermatological examination revealed urticariform pruriginous ring lesions surmounted by small peripheral vesicles spread throughout the body (Fig. 1), sparing the mucous membranes, and without Nikolsky’s sign. After two non-specific skin biopsies, the histological examination revealed an intraepidermal bubble with acantholytic cells and eosinophilic spongiosis (Figs. 2a and 2b). Direct immunofluorescence confirmed the diagnosis of pemphigus and indirect immunofluorescence was at the upper limit. The diagnosis of a PV relapse in PH was retained and a dapsone-based treatment was initiated at a dose of 150 mg/day and stopped seven days later when met with hemolytic anemia. Oral corticosteroid therapy involving prednisone at a dose of 1 mg/kg/day was initiated but, given the persistence of the pruritus, the decision was to combine methotrexate at a dose of 12.5 mg/week. A good evolution and a decline within eight months were observed. An improved pruritus and the disappearance of the skin lesions were achieved after one month of treatment. PV and PH are two different anatomical and clinical entities of the autoimmune disease pemphigus, with distinct clinical, histopathological, and immunopathological characteristics [1,2]. Our observation documents a complete phenotypic “switch” of pemphigus with a transition from PV to PH both clinically, histologically, and immunologically. Several rare cases of PV switching to superficial pemphigus (SP) (“phenotypic switch”) have, since 1991, been reported, with a higher frequency this direction than otherwise; the transition period varies from six months to twenty years [3]. To the best of our knowledge, no case has been described of a progression from PV to PH. Having observed one firsthand, we are first to describe the case of a complete phenotypic switch from PV to PH. The mechanism of such a transition remains poorly understood and is often observed during a relapse. Some authors suggest that the effect of immunosuppressants on the desmoglein DSG3 more marked than on DSG1 could explain the relapse of PS in PH [3,4]. Future studies on the immunological factors and predictors of PV relapses after the discontinuation of treatment would be useful to better understand the mechanisms of a relapse in pemphigus, with or without a phenotypic transition.

scholarly journals Serological monitoring of cattle mycoplasmosis

2020 ◽  
Vol 49 (6) ◽  
pp. 88-95
Author(s):  
M. A. Leonova ◽  
I. S. Onishchenko ◽  
N. Yu. Balybina ◽  
I. N. Pen’kova
Keyword(s):  
Enzyme Immunoassay ◽  
Carrier Phase ◽  
Active Form ◽  
Clinical Manifestations ◽  
Growth Dynamics ◽  
The Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Novosibirsk Region ◽  
Intensive Use ◽  
Chronic Course

The results of studying the immune response with persistence of the microorganism of the genus Mycoplasma in the body of cows are presented. The study (2019) was conducted in dairy farms in five districts of Novosibirsk region. Identification of individual specific antibodies of class G to microorganisms of the genus Mycoplasma was carried out in 186 samples of blood serum of cattle. The study was carried out by enzyme immunoassay with the MycoplasmaIgG antibodies ELISA VET kit. In the majority of the studied farms, a prolonged persistence of the microorganism of the genus Mycoplasma was noted. It was found that mycoplasma, having weak immunogenicity, mainly causes a chronic course of the disease. In an enzyme-linked immunoassay, this phenomenon was recorded in dubious reactions in 60.8% of animals. In some farms during the study, a period of reactivation of the disease was noted, which appeared in the transition of the disease from the carrier phase to the active form with clinical manifestations. In the enzyme immunoassay, 7.5% of the animals reacted positively. It was noted that in farms with positively reacting animals, the probability of isolation and spread of the pathogen from sick animals is high. No reaction to the presence of class G antibodies to microorganisms of the genus Mycoplasma was detected in 31.7% of the animals studied. In most farms, the growth dynamics of animals with dubious response was noted to depend on their physiological period. The connection of the duration of cow lactation with the dubious antibody response in an enzyme-linked immunosorbent assay was established. The possibility of connecting this phenomenon with highly intensive use of productive animals, which leads to an increase in stress levels and a decrease in homeostasis and immunity, is shown.

Clinical study of mucosa-associated lymphoid tissue lymphomas of the head and neck

2011 ◽  
Vol 126 (3) ◽  
pp. 271-275
Author(s):  
S Hosokawa ◽  
J Okamura ◽  
Y Takizawa ◽  
G Takahashi ◽  
K Hosokawa ◽  
...  
Keyword(s):  
Head And Neck ◽  
Surgical Resection ◽  
Lymphoid Tissue ◽  
Early Stage ◽  
Local Treatment ◽  
Response To Treatment ◽  
Limited Information ◽  
Early Stage Disease ◽  
First Choice

AbstractBackground:Limited information is available on mucosa-associated lymphoid tissue lymphomas arising in the head and neck.Method:A retrospective analysis was conducted of 20 patients who were histologically diagnosed with mucosa-associated lymphoid tissue lymphoma and treated at our institution between January 1990 and December 2009.Results:Treatment consisted of surgical resection alone in two patients (10 per cent), surgical resection with consecutive radiotherapy in one (5 per cent), and radiotherapy alone in eight (40 per cent). Three patients (15 per cent) were treated with systemic chemotherapy, and three (15 per cent) received chemoradiotherapy. Three patients (15 per cent) were informed of the diagnosis but not treated for their condition.Conclusion:All of the 20 patients were still alive after a mean follow-up period of 50.8 months. Local treatment for mucosa-associated lymphoid tissue lymphoma of the head and neck should be the first choice in early-stage disease. However, prolonged follow up is important to determine these patients' long-term response to treatment.

Molecule which changed the view on skin treatment

2021 ◽  
pp. 44-55
Author(s):  
L.Ya. Fedorich
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Local Treatment ◽  
Mechanisms Of Action ◽  
Clinical Effects ◽  
Topical Retinoids ◽  
Acne Therapy ◽  
Universal Mechanism

Objective — to study the modern classification, mechanisms of action and clinical effects of vitamin A derivatives, to analyze retinoid for local treatment of various dermatoses with a universal mechanism of action at the epidermis and dermis levels. Materials and methods. A review of the literature and an analysis of the results of international clinical trials of drugs based on the natural retinoid of the first generation — tretinoin (retinoic acid) is presented. The works of dozens of authors since 1980s to the present day are analyzed. Most sources provide detailed information on the results of topical retinoids in acne therapy, which are the base of clinical guidelines. Long-term (6 months or more) studies of retinoic acid-based preparations carried out in recent decades have discovered the unique clinical effects of tretinoin in the treatment of skin photoaging, actinic keratosis, etc. They are achieved due to the effect of tretinoid on the nuclear receptors of keratinocytes and fibroblasts. Results and discussion. The molecular mechanisms of action of retinoic acid, realizing the cellular and tissue effects of the most studied retinoid, are systematized and grouped in a single review. It has been proven that a unique feature of tretinin is its ability to activate directly all subtypes of RARs- and, indirectly, RARs-nuclear receptors of skin cells. A new modern drug for external use is presented — AltrenoТМ lotion containing micronized 0.05 % tretinoin in combination with sodium hyaluronate, soluble collagen and glycerin. This combination exhibits the expected clinical efficacy in acne therapy and prevents side effects such as dryness, redness and exfoliation. AltrenoТМ is approved for use in children of 9 years of age and older. Conclusions. Tretinoin (retinoic acid) is a modern powerful retinoid with a universal mechanism of action, recommended for the treatment of acne.

Principles of Cancer Treatment

2019 ◽  
Author(s):  
Samantha J. Baker ◽  
J. Bart Rose
Keyword(s):  
Hormone Therapy ◽  
Systemic Chemotherapy ◽  
Local Treatment ◽  
Local Environment ◽  
The Body ◽  
Isolation Techniques ◽  
Treatment Plans ◽  
Systemic Side Effects ◽  
Locoregional Therapies ◽  
Key Words Biopsy

Surgeons often play a pivotal role in the treatment plans for cancer patients, especially when the plan of action includes resection. Locoregional therapies have the advantage of treating the tumor and its local environment while minimizing systemic effects. Other examples of local treatment include radiotherapy and chemotherapy delivered with isolation techniques. In contrast, systemic chemotherapy, systemic radiation, hormone therapy, and immunotherapy are administered throughout the body. Systemic therapy is most useful in treating disease distant to the site of origin but can be limited by systemic side effects. This chapter explores each of these treatment arms in more detail and provides examples of when such options may be deployed. This review contains 1 figure, 2 tables, and 67 references. Key Words: Biopsy, Cancer, Chemotherapy, Directed therapy, Hormone therapy, Immunotherapy, Lymph nodes, Proton therapy, Radiation therapy, Staging

Vitamin D and atopic dermatitis

2021 ◽  
pp. 26-36
Author(s):  
Mariya Aleksandrovna Bochkareva ◽  
Svetlana Viktorovna Bulgakova ◽  
Anula Viktorovna Melikova
Keyword(s):  
Vitamin D ◽  
Atopic Dermatitis ◽  
Mineral Metabolism ◽  
Active Form ◽  
Allergic Diseases ◽  
The Body ◽  
Biological Processes ◽  
Skeletal System ◽  
Rapid Spread ◽  
Global Health Problem

Allergic diseases, in particular, atopic dermatitis, are becoming a global health problem due to the rapid spread, both as an independent disease and as a predictor of the development of bronchial asthma. Discovery of all the processes of the pathogenesis of atopic dermatitis will provide great opportunities for the prevention and treatment of this disease. In this regard, special attention is paid to vitamin D, which becomes more and more popular all over the world every year. In addition to the known and studied consequences of vitamin D deficiency for skeletal system health and mineral metabolism, recent studies have shown that calcitriol, the active form of vitamin D, is involved in many biological processes in the body, including the regulation of the immune system. The discovery of the vitamin D receptor on various cells of the body opens up new prospects for studying the course of various diseases, such as diabetes mellitus, vascular atherosclerosis, obesity, autoimmune diseases, oncology and allergies. The review will be devoted to this problem. 38 foreign and 2 domestic sources are cited.

scholarly journals N-Acetyl-Cysteine supplementation lowers high homocysteine plasma levels and increases Glutathione synthesis in the trans-sulfuration pathway

2019 ◽  
Vol 13 (4) ◽  
pp. 234-240
Author(s):  
Federico Cacciapuoti
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Active Form ◽  
The Body ◽  
Glutamate Cysteine Ligase ◽  
Pathological Conditions ◽  
Transsulfuration Pathway ◽  
Antioxidant Function ◽  
Acetyl Cysteine ◽  
Rate Limiting

Glutathione (GSH), a compound derived of a combination of three amino acids – cysteine, glycine and glutamine – is the final product of homocysteine (Hcy) metabolism  in the transsulfuration pathway. The major determinants of GSH synthesis are the availability of cysteine and the activity of the rate-limiting enzyme, glutamate cysteine ligase (GCL). A deficiency in  transsulfuration pathway leads to excessive Hcy production (HHcy) and reduced GSH synthesis. This tripeptide, that exists in the reduced or active  form (GSH) and oxidized variant (GSH), is the main antioxidant of the  body.  Independently of its antioxidant function, the compound  has an anti-inflammatory role too, reducing the production of interleukines and the expression of TNF-alfa and iNOS synthase. A dysregulation of GSH synthesis is recognized as contributing factor to the pathogenesis of many pathological conditions. But, the insufficiency of the transsulfuration pathway is also responsible of HHcy. Besides, this condition  decreases the activity of cellular “gluthatione peroxidase”, an intracellular antioxidant enzyme that reduces hydrogen peroxide to water with the prevalence of GSSH on GSH. The consequent GSH/GSSH impaired ratio also causes some common cardiovascular and neurodegenerative disorders. In both occurrences, N-Acetyl-Cysteine (NAC) supplementation supplies the cysteine necessary for GSH synthesis and contemporarily reduces HHcy, improving  the GPx1 activity and further reducing oxidative stress.

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