scholarly journals Mechanistic Insights on the Mechanosynthesis of Phenytoin, a WHO Essential Medicine

2021 ◽  
Author(s):  
Francesco Puccetti ◽  
Stipe Lukin ◽  
Krunoslav Užarević ◽  
Evelina Colacino ◽  
Ivan Halasz ◽  
...  
Keyword(s):  
Essential Medicine ◽  
Industrial Applications ◽  
Single Step ◽  
In Situ Monitoring ◽  
Added Value ◽  
World Health ◽  
Pharmaceutical Ingredients ◽  
Isolation And Characterization ◽  
Health Organization

In recent years, mechanochemistry has enriched the toolbox of synthetic chemists, enabling faster and more sustainable access to new materials and existing products, including active pharmaceutical ingredients (APIs). However, molecular-level understanding of most mechanochemical reactions remains limited, delaying the implementation of mechanochemistry in industrial applications. Herein, we have applied in-situ monitoring by Raman spectroscopy to the mechanosynthesis of phenytoin, a World Health Organization (WHO) Essential Medicine, enabling the observation, isolation, and characterization of key molecular-migration intermediates involved in the single-step transformation of benzil, urea, and KOH into phenytoin. This work contributes to the elucidation of a reaction mechanism that has been subjected to a number of interpretations over time and paints a clear picture of how mechanosynthesis can be applied and optimized for the preparation of added-value molecules.

Metody cytogenetyki molekularnej w różnicowaniu agresywnych B-NHL

2019 ◽  
Vol 50 (3) ◽  
pp. 109-115
Author(s):  
Beata Grygalewicz
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
World Health ◽  
High Grade ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Health Organization ◽  
Large B Cell

StreszczenieB-komórkowe agresywne chłoniaki nieziarnicze (B-cell non-Hodgkin lymphoma – B-NHL) to heterogenna grupa nowotworów układu chłonnego, wywodząca się z obwodowych limfocytów B. Aberracje cytogenetyczne towarzyszące B-NHL to najczęściej translokacje onkogenów takich jak MYC, BCL2, BCL6 w okolice genowych loci dla łańcuchów ciężkich lub lekkich immunoglobulin. W niektórych przypadkach dochodzi do wystąpienia kilku wymienionych aberracji jednocześnie, tak jak w przypadkach przebiegających z równoczesną translokacją genów MYC i BCL2 (double hit), niekiedy także z obecnością rearanżacji BCL6 (triple hit). Takie chłoniaki cechuje szczególnie agresywny przebieg kliniczny. Obecnie molekularna diagnostyka cytogenetyczna przy użyciu techniki fluorescencyjnej hybrydyzacji in situ (FISH) oraz, w niektórych przypadkach, aCGH jest niezbędnym narzędziem rozpoznawania, klasyfikowania i oceny stopnia zaawansowania agresywnych, nieziarniczych chłoniaków B-komórkowych. Technika mikromacierzy CGH (aCGH) była kluczowym elementem wyróżnienia prowizorycznej grupy chłoniaków Burkitt-like z aberracją chromosomu 11q (Burkitt-like lymphoma with 11q aberration – BLL, 11q) w najnowszej klasyfikacji nowotworów układu chłonnego Światowej Organizacji Zdrowia (World Health Organization – WHO) z 2016 r. Omówione zostaną sposoby różnicowania na poziomie cytogenetycznym takich chłoniaków jak: chłoniak Burkitta (Burkitt lymphoma – BL), chłoniak rozlany z dużych komórek B (diffuse large B-cell lymphoma – DLBCL) oraz 2 nowych jednostek klasyfikacji WHO 2016, czyli chłoniaka z komórek B wysokiego stopnia złośliwości z obecnością translokacji MYC i BCL2 i/lub BCL6 (high-grade B-cell lymphoma HGBL, with MYC and BCL2 and/or BCL6 translocations) oraz chłoniaka BLL, 11q.

scholarly journals The politics of crisis management by regional and international organizations in fighting against a global pandemic: the member states at a crossroads

2021 ◽  
pp. 002085232098451
Author(s):  
Steven Van Hecke ◽  
Harald Fuhr ◽  
Wouter Wolfs
Keyword(s):  
Crisis Management ◽  
International Organizations ◽  
Governance Structure ◽  
Added Value ◽  
World Health ◽  
The European Union ◽  
Member States ◽  
Global Pandemic ◽  
Turbulent Times ◽  
Health Organization

Despite new challenges like climate change and digitalization, global and regional organizations recently went through turbulent times due to a lack of support from several of their member states. Next to this crisis of multilateralism, the COVID-19 pandemic now seems to question the added value of international organizations for addressing global governance issues more specifically. This article analyses this double challenge that several organizations are facing and compares their ways of managing the crisis by looking at their institutional and political context, their governance structure, and their behaviour during the pandemic until June 2020. More specifically, it will explain the different and fragmented responses of the World Health Organization, the European Union and the International Monetary Fund/World Bank. With the aim of understanding the old and new problems that these international organizations are trying to solve, this article argues that the level of autonomy vis-a-vis the member states is crucial for understanding the politics of crisis management. Points for practitioners As intergovernmental bodies, international organizations require authorization by their member states. Since they also need funding for their operations, different degrees of autonomy also matter for reacting to emerging challenges, such as the COVID-19 pandemic. The potential for international organizations is limited, though through proactive and bold initiatives, they can seize the opportunity of the crisis and partly overcome institutional and political constraints.

scholarly journals Building the Case for Clopidogrel as a World Health Organization Essential Medicine

2015 ◽  
Vol 8 (4) ◽  
pp. 447-451 ◽  
Author(s):  
Amisha Patel ◽  
Mahesh Vidula ◽  
Sunny P. Kishore ◽  
Rajesh Vedanthan ◽  
Mark D. Huffman
Keyword(s):  
World Health Organization ◽  
Essential Medicine ◽  
World Health ◽  
Health Organization

scholarly journals Giant Cell Urothelial Carcinoma of Bladder

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Harshima Disvini Wijesinghe ◽  
Ajith Malalasekera
Keyword(s):  
Urothelial Carcinoma ◽  
Giant Cell ◽  
Early Stage ◽  
Giant Cells ◽  
World Health ◽  
World Health Organization Classification ◽  
Health Organization

Giant cell urothelial carcinoma is a rare variant of bladder cancer recognized by the current World Health Organization classification of urologic tumours. It is an aggressive tumour with a poor prognosis that usually presents at an advanced stage. It is characterized histologically by pleomorphic giant cells. We discuss a case of giant cell urothelial carcinoma presenting at an early stage in a previously well 62-year-old woman. Histology showed a tumour comprising pancytokeratin positive bizarre mononuclear and multi-nuclear giant cells admixed with areas of conventional urothelial carcinoma and carcinoma in situ. Three-month follow-up cystoscopy and magnetic resonance imaging showed no evidence of recurrence or pelvic lymphadenopathy.

scholarly journals Recently Described and Clinically Important Entities in Testis Tumors: A Selective Review of Changes Incorporated Into the 2016 Classification of the World Health Organization

2018 ◽  
Vol 143 (6) ◽  
pp. 711-721 ◽  
Author(s):  
Thomas M. Ulbright
Keyword(s):  
Germ Cell ◽  
World Health Organization ◽  
Cell Tumor ◽  
World Health ◽  
Sertoli Cell Tumor ◽  
Trophoblastic Tumor ◽  
The World ◽  
Health Organization

Context.— In 2016 the World Health Organization published a revised classification of testicular neoplasms based upon advances in understanding their pathogenesis and molecular biology. The rationale for this revision and additional clinically relevant observations were the topics of a talk given to the Houston Society of Clinical Pathologists in April 2017. This paper summarizes that talk. Objective.— To summarize and explain the most important changes to the classification of testicular neoplasms in the World Health Organization 2016 revision. Data Sources.— Peer-reviewed published literature and contributions by individuals with expertise in this area that were also reviewed by genitourinary pathologists. Conclusions.— Most changes occurred in the germ cell tumor classification, including replacement of the terms intratubular germ cell neoplasia unclassified and carcinoma in situ by germ cell neoplasia in situ; subdivision of the tumors into 2 main categories, those derived from germ cell neoplasia in situ and those not derived from germ cell neoplasia in situ; distinction of germ cell neoplasia in situ from germ cells with delayed maturation and pre–germ cell neoplasia in situ; expansion of the trophoblastic tumor category to include epithelioid trophoblastic tumor and cystic trophoblastic tumor; and substitution of spermatocytic tumor for spermatocytic seminoma and its placement in the non–germ cell neoplasia in situ group. Other revisions included eliminating sclerosing Sertoli cell tumor as a distinct entity; the recognition of intratubular hyalinizing Sertoli cell tumor; and acceptance of the role of undifferentiated gonadal tissue in the pathogenesis of gonadoblastoma.

scholarly journals Drug utilization patterns of antidepressants in Federal Neuro-Psychiatric Hospital Lagos, Nigeria

2017 ◽  
Vol 6 (5) ◽  
pp. 12 ◽  
Author(s):  
Oyinlade A. Kehinde ◽  
Emmanuel N. Anyika ◽  
Isaac Abah
Keyword(s):  
Average Cost ◽  
Treatment Guidelines ◽  
Tertiary Care ◽  
Essential Medicine ◽  
Prescribing Patterns ◽  
World Health ◽  
Rational Drug ◽  
Generic Prescribing ◽  
Cost Of Drugs ◽  
Health Organization

Backgroud: The paucity of information on prescribing patterns and use of antidepressants in accordance with practice guidelines necessitated this study in Nigeria.Objective: To assess the prescribing patterns of antidepressants, average cost of prescriptions and the index of rational drug prescribing (IRDP) in a Nigerian tertiary care hospital.Methods: A retrospective study which involved the assessment of 683 prescriptions and case records of patients who received antidepressants from 1st January 2013 to 31st December 2014 was conducted. Information on diagnosis, patients’ demographics, prescribing patterns and cost of medications was obtained therefrom. Compliance to the World Health Organization (WHO) prescribing indicators and Nigerian Standard Treatment Guidelines (STG) was assessed. The IRDP for antdepressants was determined using a validated mathematical model. The statistical analysis was performed using SPSS version 20.Results: Tricyclic antidepressants (TCAs) were the most commonly prescribed drug group (61.3%), followed by selective serotonin re-uptake inhibitors (SSRIs) with a total of 38.7%. On the average, three drugs were prescribed per prescription, while 60.3% and 38.3% of the drugs were prescribed from National Essential Medicine List (NEML) and STG respectively. The IRDP was 3.96 over 5 points. The average cost of drugs per prescription was 4.2 USD. The cost of drugs in the prescriptions written according to STG was lower compared to that in prescriptions not compliant with the STG (p < .001).Conclusions: TCAs are the most commonly prescribed antidepressants due to their affordability. The generic prescribing, medicines prescribed from the NEML and in compliance with the STG were less than the WHO standard. The rational drug use is suboptimal. Better prescribing habits, affordability and use of newer antidepressants should be encouraged by the hospital management.

Can luteolin be a therapeutic molecule for both colon cancer and diabetes?

2018 ◽  
Vol 18 (4) ◽  
pp. 230-239 ◽  
Author(s):  
Rashmi K Ambasta ◽  
Rohan Gupta ◽  
Dhiraj Kumar ◽  
Saurabh Bhattacharya ◽  
Aditi Sarkar ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
World Health ◽  
Molecular Signaling ◽  
Immunofluorescence Analysis ◽  
Number Of Patients ◽  
Patients With Diabetes ◽  
Health Organization ◽  
Multiple Signaling

Abstract Diabetes and colon cancer are the leading cause of mortality worldwide. According to World Health Organization, the number of patients with diabetes and cancer is going to be elevated by 50% in 2020. However, several flavonoids have been known to be useful in reducing the chance of cancer/diabetes but the hunt of a single biomolecule that can act as therapeutic and preventive molecules for future epidemic continues. In this review, we aim to perform an illustration of all researches done that target molecular signaling using luteolin in cancer/diabetes and predicted target protein using PharmMapper. The search confirms that luteolin can be a remedial molecule for both cancer and diabetes via acting on variety of signaling pathway. Furthermore, we also intend to illustrate/compare the predicted and verified molecular modes of action of luteolin. Fluorescence in situ hybridization analysis confirms the expression of CCND1 in colon cancer while immunofluorescence analysis confirms the CDK4 in diabetes. Finally, an effort has been made to map docking of marker protein-luteolin at a particular site using docking software. This review gives a holistic overview about luteolin as a therapeutic molecule for cancer/diabetes via acting on multiple signaling cascade such as p53, Wnt, eNOS, iNOS, SOD and MMP9, with especial emphasis on the cyclin-CDK pathway. Altogether, the review concludes that luteolin can be a molecule for the therapy of both cancer and diabetes by acting on broad signaling pathway.

scholarly journals Getting Histoplasmosis on the Map of International Recommendations for Patients with Advanced HIV Disease

2019 ◽  
Vol 5 (3) ◽  
pp. 80 ◽  
Author(s):  
Bongomin ◽  
Kwizera ◽  
Denning
Keyword(s):  
Fungal Infections ◽  
Universal Access ◽  
Essential Medicine ◽  
Public Health Problem ◽  
World Health ◽  
Disseminated Histoplasmosis ◽  
Life Threatening Illness ◽  
Global Action ◽  
Health Organization ◽  
Advanced Hiv Disease

Progressive disseminated histoplasmosis, caused by H. capsulatum, is a life-threatening illness and is an AIDS-defining opportunistic infection. It is neglected, worryingly under-diagnosed, and often misdiagnosed as cancer or tuberculosis with fatal consequences. Globally, over 100,000 cases of disseminated histoplasmosis have been estimated. In 2017, the World Health Organization (WHO) noted that disseminated histoplasmosis is a significant cause of mortality in AIDS patients. Through the rigorous efforts of the Global Action Fund for Fungal Infections (GAFFI) and partners, in 2019, the Histoplasma antigen test was included on the 2nd Edition of the WHO List of Essential Diagnostics. The drugs used in the treatment of histoplasmosis (amphotericin B and itraconazole) are on the WHO Essential Medicine List. The Manaus Declaration on histoplasmosis in the Americas and the Caribbean, where histoplasmosis kills more people with HIV than tuberculosis, advocates for universal access to rapid testing for histoplasmosis and availability of essential drugs for the treatment of histoplasmosis in every country by 2025. Hyperendemic areas are present in the Americas, Caribbean, Southeast Asia, and Latin America. In conclusion, histoplasmosis remains an important clinical and public health problem. To reduce HIV-associated mortality, disseminated histoplasmosis must be addressed through advocacy, increased awareness, and universal access to essential diagnostics and antifungal agents.

Incidence of Bone Marrow (BM) Fibrosis in Multiple Myeloma (MM) Patients and Its Relationship to Cytogenetic (CG) Abnormalities in a Minority Population

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5077-5077
Author(s):  
Gurinder Sidhu ◽  
Rabia Latif ◽  
Jinli Liu ◽  
Constantine Axiotis ◽  
Ratesh Khillan ◽  
...  
Keyword(s):  
African American ◽  
Conflicts Of Interest ◽  
World Health ◽  
Minority Population ◽  
Kings County ◽  
Cytogenetic Data ◽  
The World ◽  
Grade 3 ◽  
Health Organization

Abstract Abstract 5077 Background: The incidence of BM fibrosis in MM is low and uncertain, and its causes are not known. Cytogenetic and fluorescence in situ hybridization (FISH) in some MM patients reveals prognostically significant anomalies. Methods: Records of patients with MM seen at Kings County Hospital from 2004 through 2010 were reviewed, the histological sections of patients reported to have fibrosis we re-examined. The degree of fibrosis was graded according to the World Health Organization system. Results: Records of 113 patients were reviewed, 110 (97%) were African American (AA). Of these, 62 (55%) were female and 51 (45%) male. Their age ranged (median 65) from 38 to 89 years. Cytogenetic data (CGD) was available in 46 patients; and abnormal in 10 (22%) and normal in 36 (78%) of those. All patients with abnormalities of chromosomal number were hyperdiploid. Of 113 patients, 62 (55%) were female, 110 were African American. Ages ranged from 38–89 (median 65) years. Cytogenetic data was available for 46 patients and abnormal in 10 (22%). All patients with abnormal chromosome numbers were hyperdiploid. FISH studies to detect abnormalities in chromosomes 13, 14 and 17 were available in 25 and abnormal in 2 (8%). BM fibrosis had been initially noted in 27 of 113 patients (24%), and confirmed by another hematopathologist; 17 (63%) were women. The ages of the patients with fibrosis ranged from 4–79 years: median age was 67, 67 for the women and 62 for the men. Focal and grades 1, 2 and 3 fibrosis were noted in 2 (7%), 12 (44%), 7 (26%) and 6 (22%) of patients. Grade 3 fibrosis was found in 24% of the women and 20% of the men with fibrosis. CG data was available for 17 fibrosis patients and abnormal (hyperdipliod) in 2 (18%). FISH studies for chromosomes 13, 14 and 17 were normal in the 7 patients studied. CGD for all 8 of the female fibrosis patients studied were normal, and abnormal in 2 of the 9 men (22%). Conclusions: Of our 113 AA myeloma patients 25% had detectable BM fibrosis, but it was grade 3 in only 5%. Female preponderance was more marked in the patients with fibrosis than in the whole MM group. CG and FISH data did not distinguish patients with and without fibrosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Multimodality Technologies in the Assessment of Hematolymphoid Neoplasms

2017 ◽  
Vol 141 (3) ◽  
pp. 341-354 ◽  
Author(s):  
Shiyong Li ◽  
David L. Jaye ◽  
Kyle T. Bradley ◽  
Linsheng Zhang ◽  
Debra Saxe ◽  
...  
Keyword(s):  
World Health ◽  
Initial Assessment ◽  
Additional Information ◽  
Appropriate Treatment ◽  
Disease Entities ◽  
Minimal Disease ◽  
Health Organization ◽  
Hematolymphoid Neoplasms ◽  
Immunophenotypic Analysis

Accurate assessment of tissues for hematolymphoid neoplasms requires an integrated multiparameter approach. Although morphologic examination by light microscopy remains the mainstay of initial assessment for hematolymphoid neoplasms, immunophenotypic analysis by immunohistochemistry and/or flow cytometry is essential to determine the pattern of differentiation and to detect minimal disease when morphology is inconclusive. In some cases, immunophenotypic analysis provides additional information for targeted immunotherapy and prognostication. Genotypic studies, including cytogenetics, fluorescence in situ hybridization, DNA microarray, polymerase chain reaction, and/or next-generation sequencing, are also imperative for subclassification of the genetically defined disease entities in the current World Health Organization classification of hematolymphoid neoplasms. Moreover, genotypic studies can establish clonality, stratify patients to determine appropriate treatment, and monitor patients for treatment response.

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