scholarly journals Synthetic analogs of vitamin D3 in therapy of psoriasis

2018 ◽  
Vol 16 (4) ◽  
pp. 49-54
Author(s):  
Inna V. Petrova ◽  
Rasul M. Radzhabov ◽  
Abdul R. Abdulov ◽  
Magomed G. Manatov ◽  
Ruslan I. Glushakov ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Vitamin D3 ◽  
Skin Diseases ◽  
Interleukin 2 ◽  
Clinical Manifestations ◽  
New Drugs ◽  
Epidermal Keratinocytes ◽  
Synthetic Analogue ◽  
Therapeutic Activity ◽  
Inhibition Of Proliferation

Psoriasis is one of the most common skin diseases and occurs in 1-2% of the population of developed countries. The problem of pathogenetic treatment of psoriasis remains relevant despite the annual appearance of new drugs. The anti-keratinizing effect is particularly important in the treatment of psoriasis. The effect is based on suppression of the proliferation of epidermal keratinocytes, normalization of the differentiation of the nonkeratinizing epithelium and the decrease in the adhesion of horny cells. The last decade is characterized by a deepening of ideas about the biological properties and mechanism of action of vitamin D3. However the vitamin D3 does itself not have therapeutic activity. In this connection the use of synthetic analogues of vitamin D3 which have therapeutic activity is particular of importance. The aim. To evaluate the effectiveness of vitamin D3synthetic analogs for the treatment of psoriasis. Methods. It was retrospective analysis of multicentric studies by a double-blind, randomized method of the effectiveness of vitamin D3 analogs for the treatment of psoriasis in Russia and foreign clinics. The PASI index in assessing the clinical manifestations of psoriasis. Rеsults and discussion. The study of the clinical efficacy of oral forms of the vitamin indicates a positive therapeutic effect in 70-90% of patients but this requires an average of 2.8 months. Therefore for the treatment of psoriasis more widely used synthetic analogue of vitamin D3 – calcipotriol (MS-903), developed exclusively for topical application. Calcipotriol gives minimal side effects and has an intense antipsoriatic effect. The mechanism of action of calcipotriol is based on interaction with specific receptors on keratinocytes which causes inhibition of proliferation, accelerates the morphological differentiation of psoriatic cells, inhibits the activity of interleukin-1 and reduces interleukin-2 production, i.e. has an effect on the pathogenetic mechanisms of psoriasis. Conclusion. Vitamin D3 analogues are effective antipsoriatic drugs that can be used both as monotherapy and in the complex treatment of patients with severe psoriasis.

scholarly journals AgNP-PVP-meglumine antimoniate nanocomposite reduces Leishmania amazonensis infection in macrophages

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ana Patricia Cacua Gélvez ◽  
José Antonio Picanço Diniz Junior ◽  
Rebecca Thereza Silva Santa Brígida ◽  
Ana Paula Drummond Rodrigues
Keyword(s):  
Mechanism Of Action ◽  
Clinical Manifestations ◽  
Leishmania Amazonensis ◽  
New Drugs ◽  
Chemokine Production ◽  
Meglumine Antimoniate ◽  
Membrane Rupture ◽  
Material Deposition ◽  
Species Production

Abstract Background Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and presents different clinical manifestations. The adverse effects, immunosuppression and resistant strains associated with this disease necessitate the development of new drugs. Nanoparticles have shown potential as alternative antileishmanial drugs. We showed in a previous study the biosynthesis, characterization and ideal concentration of a nanocomposite that promoted leishmanicidal activity. In the present study, we conducted a specific analysis to show the mechanism of action of AgNP-PVP-MA (silver nanoparticle–polyvinylpyrrolidone-[meglumine antimoniate (Glucantime®)]) nanocomposite during Leishmania amazonensis infection in vitro. Results Through ultrastructural analysis, we observed significant alterations, such as the presence of small vesicles in the flagellar pocket and in the extracellular membrane, myelin-like structure formation in the Golgi complex and mitochondria, flagellum and plasma membrane rupture, and electrodense material deposition at the edges of the parasite nucleus in both evolutive forms. Furthermore, the Leishmania parasite infection index in macrophages decreased significantly after treatment, and nitric oxide and reactive oxygen species production levels were determined. Additionally, inflammatory, and pro-inflammatory cytokine and chemokine production levels were evaluated. The IL-4, TNF-α and MIP-1α levels increased significantly, while the IL-17 A level decreased significantly after treatment. Conclusions Thus, we demonstrate in this study that the AgNP-PVP-MA nanocomposite has leishmanial potential, and the mechanism of action was demonstrated for the first time, showing that this bioproduct seems to be a potential alternative treatment for leishmaniasis.

Mycobacteriosis as a Healthcare-Associated Infection: A Review of Epidemiologic Studies

2020 ◽  
pp. 37-41
Author(s):  
IV Petrov ◽  
TKh Amirova ◽  
LV Petrova ◽  
FS Petrova
Keyword(s):  
Skin Diseases ◽  
Nontuberculous Mycobacteria ◽  
Clinical Manifestations ◽  
Mycobacterial Infection ◽  
Epidemiologic Studies ◽  
Health Facilities ◽  
Water Supply Systems ◽  
Healthcare Associated Infections ◽  
Healthcare Associated Infection ◽  
Healthcare Associated

Introduction: Healthcare-associated infections are of great socio-economic importance and are characterized by a large number of different pathogens. Nontuberculous mycobacteria are ubiquitous microorganisms that can circulate in a medical organization. The purpose of this review of epidemiologic studies was to establish the main features of mycobacteriosis as a healthcare-associated infection, taking into account the significance of the results and the compliance of the reviewed studies with the criteria of evidence-based medicine. Methods: We did a key word search for “nontuberculous mycobacteria”, “healthcare-associated infections”, and “mycobacteriosis” in several electronic bibliographic databases including Web of Science, PubMed, eLIBRARY, and ResearchGate and selected 127 out of 342 search results. Having analyzed the selected articles, we decided to include 34 of them in this study according to the topic of work. We established that nontuberculous mycobacteria can be found in various objects of health facilities, e.g. water supply systems, medical products and equipment. We also found that mycobacterial infection of nosocomial etiology could have various clinical manifestations (arthritis, keratitis, circulatory and skin diseases, etc.) determined by various aspects, such as heterogeneity of the group of nontuberculous mycobacteria, portals of entry (surgical procedures on various organs and systems of the human body, etc.), pathways of exposure and transmission factors. Resistance of nontuberculous mycobacteria to a number of disinfectants is a special question defining the importance of profound research in terms of ensuring sanitary and anti-epidemic (disinfection) safety within health facilities. Conclusions: Our findings indicate that mycobacterial infection can be considered as a healthcare-associated infection requiring an in-depth assessment from various perspectives including a microbiological monitoring of medical objects, statistical accounting of nosocomial infections, and clinical alertness in the diagnosis of mycobacteriosis by attending physicians and bacteriologists, etc.

scholarly journals The Main Challenges in Systemic Lupus Erythematosus: Where Do We Stand?

2021 ◽  
Vol 10 (2) ◽  
pp. 243
Author(s):  
Matteo Piga ◽  
Laurent Arnaud
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Unmet Need ◽  
Clinical Manifestations ◽  
New Drugs ◽  
Systemic Lupus ◽  
Major Step ◽  
Damage Accrual

Systemic lupus erythematosus (SLE) is an immune-mediated multi-systemic disease characterized by a wide variability of clinical manifestations and a course frequently subject to unpredictable flares. Despite significant advances in the understanding of the pathophysiology and optimization of medical care, patients with SLE still have significant mortality and carry a risk of progressive organ damage accrual and reduced health-related quality of life. New tools allow earlier classification of SLE, whereas tailored early intervention and treatment strategies targeted to clinical remission or low disease activity could offer the opportunity to reduce damage, thus improving long-term outcomes. Nevertheless, the early diagnosis of SLE is still an unmet need for many patients. Further disentangling the SLE susceptibility and complex pathogenesis will allow to identify more accurate biomarkers and implement new ways to measure disease activity. This could represent a major step forward to find new trials modalities for developing new drugs, optimizing the use of currently available therapeutics and minimizing glucocorticoids. Preventing and treating comorbidities in SLE, improving the management of hard-to-treat manifestations including management of SLE during pregnancy are among the remaining major unmet needs. This review provides insights and a research agenda for the main challenges in SLE.

scholarly journals Mechanism of Action of CM-55, a Synthetic Analogue of the Antilipogenic Antibiotic Cerulenin

1974 ◽  
Vol 6 (4) ◽  
pp. 387-392 ◽  
Author(s):  
T. Ohno ◽  
J. Awaya ◽  
T. Kesado ◽  
S. Nomura ◽  
S. Omura
Keyword(s):  
Mechanism Of Action ◽  
Synthetic Analogue

scholarly journals PUVA bath therapy strongly suppresses immunological and epidermal activation in psoriasis: a possible cellular basis for remittive therapy.

1994 ◽  
Vol 180 (1) ◽  
pp. 283-296 ◽  
Author(s):  
V P Vallat ◽  
P Gilleaudeau ◽  
L Battat ◽  
J Wolfe ◽  
R Nabeya ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Interleukin 2 ◽  
Epidermal Keratinocytes ◽  
Therapeutic Effects ◽  
Sustained Remission ◽  
Puva Therapy ◽  
Cellular Basis ◽  
Bath Therapy ◽  
Puva Treatment

Psoriasis is characterized by alterations in both the epidermis and dermis of the skin. Epidermal keratinocytes display marked proliferative activation and differentiate along an "alternate" or "regenerative" pathway, while the dermis becomes infiltrated with leukocytes, particularly interleukin 2 (IL-2) receptor-bearing "activated" T cells. Psoralens, administered by the oral route, have therapeutic effects in psoriasis when photochemically activated by ultraviolet A light (PUVA therapy). Recently psoralen bath therapy has been introduced to more effectively deliver this agent to the diseased skin. We have correlated the efficacy of PUVA bath therapy with its effects on specific molecular and cellular parameters of disease, in 10 consecutive patients with recalcitrant psoriasis. Rapid clearing of lesions occurred in 8 out of 10 patients. Biopsies were taken from lesional and nonlesional skin before and after a single round of therapy, and observation was continued in our Clinical Research Center at The Rockefeller University. Enumeration of cycling keratinocytes with the Ki-67 monoclonal antibody showed that PUVA reduced cell proliferation by 73%. The pathological increase in insulin-like growth factor 1 (IGF-1) receptors was reversed, whereas epidermal growth factor (EGF) receptors, which are also increased in psoriasis, remained unchanged. Keratinocyte proteins that are expressed in abnormal sites of the epidermis during psoriasis, i.e., keratin 16, filaggrin, and involucrin, were, after PUVA treatment, localized to their normal sites. Epidermal and dermal T-lymphocytes (CD3+), as well as CD4+, CD8+, and IL-2 receptor+ subsets, were strongly suppressed by PUVA, with virtual elimination of IL-2 receptor+ T cells in some patients. Consistent with diminished lymphocyte activation, HLA-DR expression by epidermal keratinocytes was markedly reduced in treated skin. In comparison to cyclosporine treatment of psoriasis, PUVA therapy leads to more complete reversal of pathological epidermal and lymphocytic activation, changes which we propose to be the cellular basis for a more sustained remission of disease after PUVA treatment.

scholarly journals Lymphokine abnormalities in aplastic anemia: implications for the mechanism of action of antithymocyte globulin

Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 407-413
Author(s):  
P Gascon ◽  
NC Zoumbos ◽  
G Scala ◽  
JY Djeu ◽  
JG Moore ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Mechanism Of Action ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Lymphocyte Function ◽  
Normal Range ◽  
Flow Microfluorometry ◽  
Nonadherent Cells ◽  
Hematopoietic Response

Anti-thymocyte globulin (ATG) provides effective therapy for many patients with aplastic anemia, and its mechanism of action has been presumed to be secondary to lymphocytotoxicity. However, our studies of lymphocyte function in aplastic anemia show marked abnormalities of lymphokine production, which ATG may modulate. In 12 of 17 patients with aplastic anemia, interleukin 2 (IL2) production was markedly elevated in vitro (P less than .01 by paired statistical analysis). Expression of the IL2 receptor, or Tac antigen, on peripheral lymphocytes assessed by flow microfluorometry was also increased above the normal range in 11 of 15 cases. Studies of ATG suggested that it might act to stimulate lymphocyte function. In vitro, ATG is a mitogen, as measured by incorporation of 3H-thymidine into blood mononuclear cells; the response of cells to ATG from patients with aplastic anemia was exaggerated in comparison with normals. Cell proliferation was accompanied by production of IL2 to levels that were, in some cases, similar to those obtained with lectin stimulation. Finally, supernatants from lymphocytes cultured in the presence of ATG were able to replace adherent cells in providing growth factors for the support of nonadherent cells in methylcellulose hematopoietic colony assays. These results provide a mechanism for an “immunostimulatory” action of ATG in effecting hematopoietic response in some patients with aplastic anemia.

scholarly journals Target Therapy in Acute Myeloid Leukemia

2020 ◽  
Author(s):  
Vasko Graklanov
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Acute Leukemia ◽  
Mechanism Of Action ◽  
Myeloid Leukemia ◽  
Target Therapy ◽  
New Drugs ◽  
Cytotoxic Treatment ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is the most common form of acute leukemia in elderly patients. Over the past four decades the basic therapeutic armamentarium was the standard cytotoxic treatment. The new insights in understanding the pathogenesis of AML was the momentum that revolutionized the treatment landscape in AML. The last five years unprecedented growth has been seen in the number of target therapy drugs for the treatment of AML. These new drugs did not just have a clinical benefit as single agents but also have improved AML patient outcomes if combined with conventional cytotoxic therapy. Here, we review recent advances in target-based therapy for patients with AML focusing on their mechanism of action and the results from already published clinical trials.

scholarly journals The Frequency and Causes of Subepidermal Gaps or Blisters and the Compliance Rate Between Clinical Diagnosis and Pathology Reports from 2015 to 2019

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Abbas Darjani ◽  
Hojat Eftekhari ◽  
Seyedeh Rojin Amini Rad ◽  
Narges Alizadeh ◽  
Rana Rafiee ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Skin Diseases ◽  
Histopathological Examination ◽  
Compliance Rate ◽  
Clinical Manifestations ◽  
Final Diagnosis ◽  
Direct Immunofluorescence ◽  
Diagnostic Challenge ◽  
Cross Sectional ◽  
Pathology Reports

Background: Skin diseases are the fourth most common cause of human illness, and blisters with different clinical manifestations make a diagnostic challenge. Objectives: This study aimed to evaluate the frequency and causes of subepidermal gaps or blisters, as well as the compliance rate between the initial and final clinical diagnoses based on pathology reports. Methods: In this cross-sectional study, pathology reports of subepidermal blisters or gaps were evaluated in the patients referred to the Razi Laboratory of Rasht from 2015 to 2019. The samples were examined by a pathologist after hematoxylin and eosin staining. The reports included demographic information, clinical differential diagnoses, final diagnosis, direct immunofluorescence findings, and salt split results. Finally, the compliance rate of clinical diagnosis with pathology reports was determined. Results: A total of 183 pathology reports were evaluated, 170 of which contained the final diagnosis. Females were more frequently affected by the disease, and pemphigoid bolus and lichen planus were the most prevalent final diagnoses. The compliance rate between the initial and final diagnoses was 94%. About 37.2% of the reports lacked direct immunofluorescence (DIF) and salt split, and only 42.6% of the samples had undergone DIF examination, while 20.2% had both DIF and salt split. There was no significant association between the compliance rate of the final diagnosis with age, sex, and undergoing diagnostic tests. Conclusions: A high incidence of subepidermal gaps or blisters was seen in middle-aged individuals and females. The compliance rate of the initial clinical diagnosis with the final diagnosis based on pathological reports was high. Our findings emphasize the importance of histopathological examination and the complementary role of direct immunofluorescence and salt split in diagnosis.

scholarly journals Hemophagocytic Lymphohistiocytosis Syndrome As Presenting Sign For Acute Monocytic Leukaemia- A Case Report.

2020 ◽  
Vol 7 (08) ◽  
pp. 4918-4924
Author(s):  
Gal Sahaf Levin ◽  
Gida Ayada ◽  
Moshe Yeshurun ◽  
Oleg Rogach ◽  
Shaul Lev
Keyword(s):  
Acute Myeloid Leukemia ◽  
Organ Failure ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Myeloid Leukemia ◽  
Case Reports ◽  
Transitional Cell ◽  
Interleukin 2 ◽  
Clinical Manifestations ◽  
Multi Organ Failure ◽  
Acute Myeloid

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare aggressive syndrome of excessive immune activation. Clinical manifestations of this syndrome mimic various other clinical conditions making the diagnosis harder to achieve. These manifestations are believed to be a result of cytokine storm which leads, eventually, to a multi-organ failure and eventually death. The latter two might be prevented if HLH was diagnosed early. HLH is classified into primary consist of monogenic disorders and secondary occurs as a complication in various settings such as infection, autoimmune disease, and malignancy. In hematologic malignancies, HLH is classically associated with specific entities, mainly, lymphoma or induced by treatment-related infections. Acute myeloid leukemia, on the other hand, is less common trigger with only few case reports.   Case presentation: An 83-years-old, 5 years free of transitional cell man, presented with unstable atrial fibrillation was intubated and shortly after that he developed a multi-organ failure. Bicytopenia and a high level of ferritin aroused a clinical suspicion of HLH syndrome. Further evaluation revealed high levels of soluble interleukin 2 receptors and no activity of natural killers cells. A bone marrow was performed and it did not show phagocytosis, however, acute myeloid leukemia (AML) was diagnosed. AML was suggested to be associated with chemotherapy that our patient received 5 years earlier.   Conclusion: Hemophagocytic lymphohistiocytosis can be present as a multi-organ failure requiring a high index of suspicion. Chemotherapy related-AML can be a trigger for HLH. 

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