Influence of excipients on absorbtion from soft pharmaceuticals forms

Catedra de tehnologie a medicamentelor, Universitatea de Stat de Medicină și Farmacie „Nicolae Testemițanu” din Republica MoldovaIntroducere. Datorită incidenței crescute a afecțiunilor de piele, în rândul populației din RM una din problemele majore ale cercetărilor din domeniul farmaceutic este elaborarea de noi forme farmaceutice și studiul naturii diferitor excipienți asupra procesului de absorbție. În acest sens au fost studiați diferiți excipienți în forme farmaceutice moi, în scopul dezvoltării terapiei afecțiunilor de piele. Scopul lucrării. În acest studiu ne-am propus ca scop studiul excipienților și influența acestora în absorbția cutanată a formelor farmaceutice moi. Material și metode. Drept materiale au servit diverse reviste de specialitate contemporane din diferite țări și din RM. Rezultate. În urma analizei datelor din literatura de specialitate am constatat că din punct de vedere a biodisponibilității și al eficacității, excipienții folosiți la prepararea formelor medicamentoase moi influențează în mod vădit absorbția substanțelor medicamentoase active prin piele. Absorbția prin piele este un proces complex, dinamic, orice modificare a conținutului substanței active, a excipienților, poate schimba fluxul substanțelor active în zona cutanată. Concluzii. Excipienții folosiți la prepararea formelor medicamentoase moi pot schimba starea fizică și permeabilitatea stratului cornos, în special prin efectul oclusiv, mărind conținutul ăn umiditate din piele, poate îmbunătăți penetrarea substanțelor active. Dintre bazele de unguent, cele mai oclusive sunt bazele grase, anhidre apoi emulsii A/U și cu efect mai mic emulsii U/A. Asupra absorbtiei percutanate, de asemenea pot influența promotorii de absorbție din compoziția excipienților.Introduction. Due to the increased incidence of skin affections, among the population of the Republic of Moldova, one of the major problems of pharmaceutical research is the development of new soft pharmaceutical forms and the study of nature of different excipients in soft pharmaceutical forms for the development of skin disorders therapy. The aim of the study. In this study we aimed to study excipients and their influence on cutaneous absorption of soft pharmaceutical forms. Material and methods. As materials served various contemporary scientific journals from the Republic of Moldova and different countries. Results. Following the information and analysis from the scientific, specialized literature, we have found that from the bioavaibility and efficacy point of view, the excipients used for preparation of soft pharmaceutical forms influence obviously absorbtion of active drug substances through skin. The absorption through skin is a complex, dynamic process, any content modification of the active substance, of the excipients, can change the rate of penetration of active substance into cutaneous area. Conclusions. Excipients used for the preparation of soft drug forms can change the physical state and permeability of stratum corneum, especially by the occlusive effect, increasing the moisture content of the skin, it can improve the penetration of active substances. From the ointment bases, the most occlusive ones are the fatty bases, anhydrous, then W/O emulsions and with a lesser effect O/W emulsions

A PUF-based cryptographic security solution for IoT systems on chip

The integration of multicore processors and peripherals from multiple intellectual property core providers as hardware components of IoT multiprocessor systems-on-chip (SoC) represents a source of security vulnerabilities for the in-chip communication. This paper describes the concept and the practical results of a SoC security implementation that is illustrative for IoT applications. The mechanism employed in this approach uses physically unclonable functions (PUF) and symmetric cryptography in order to encrypt the transferred messages within the SoC between the microprocessor and its peripherals. The mechanism is experimentally validated at FPGA level, the paper describing also an implementation scenario for an IoT ARM based device

Trace semantics via determinization

This paper takes a fresh look at the topic of trace semantics in the theory of coalgebras. The first development of coalgebraic trace semantics used final coalgebras in Kleisli categories, stemming from an initial algebra in the underlying category (see notably~\cite{HasuoJS07}). This approach requires some non-trivial assumptions, like dcpo enrichment, which do not always hold, even in cases where one can reasonably speak of traces (like for weighted automata). More recently, it has been noticed (see~\cite{SBBR10}) that trace semantics can also arise by first performing a determinization construction. In this paper, we develop a systematic approach, in which the two approaches correspond to different orders of composing a functor and a monad, and accordingly, to different distributive laws. The relevant final coalgebra that gives rise to trace semantics does not live in a Kleisli category, but more generally, in a category of Eilenberg-Moore algebras. In order to exploit its finality, we identify an extension operation, that changes the state space of a coalgebra into a free algebra, which abstractly captures determinization of automata. Notably, we show that the two different views on trace semantics are equivalent, in the examples where both approaches are applicable.We are grateful to the anonymous referees for valuable comments. The work of Alexandra Silva is partially funded by the ERDF through the Programme COMPETE and by the Portuguese Foundation for Science and Technology, project Ref. FCOMP-01-0124-FEDER-020537 and SFRH/BPD/71956/2010

Design, Synthesis and Biological Activity Evaluation of S-Substituted 1H-5-Mercapto-1,2,4-Triazole Derivatives as Antiproliferative Agents in Colorectal Cancer

Colon cancer is a widespread pathology with complex biochemical etiology based on a significant number of intracellular signaling pathways that play important roles in carcinogenesis, tumor proliferation and metastasis. These pathways function due to the action of key enzymes that can be used as targets for new anticancer drug development. Herein we report the synthesis and biological antiproliferative evaluation of a series of novel S-substituted 1H-3-R-5-mercapto-1,2,4-triazoles, on a colorectal cancer cell line, HT-29. Synthesized compounds were designed by docking based virtual screening (DBVS) of a previous constructed compound library against protein targets, known for their important role in colorectal cancer signaling: MEK1, ERK2, PDK1, VEGFR2. Among all synthesized structures, TZ55.7, which was retained as a possible PDK1 (phospholipid-dependent kinase 1) inhibitor, exhibited the most significant cytotoxic activity against HT-29 tumor cell line. The same compound alongside other two, TZ53.7 and TZ3a.7, led to a significant cell cycle arrest in both sub G0/G1 and G0/G1 phase. This study provides future perspectives for the development of new agents containing the 1,2,4-mercapto triazole scaffold with antiproliferative activities in colorectal cancer

Preparing for pandemics: a systematic review of pandemic influenza clinical management guidelines

Background: The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and mortality by improving the quality of clinical decisions. This systematic review aims to evaluate the availability, inclusivity, and quality of pandemic influenza CMGs, to identify gaps that can be addressed to strengthen pandemic preparedness in this area. Methods: Ovid Medline, Ovid Embase, TRIP (Turning Research Into Practice), and Guideline Central were searched systematically from January 2008 to 23rd June 2022, complemented by a grey literature search till 16th June 2022. Pandemic influenza CMGs including supportive care or empirical treatment recommendations were included. Two reviewers independently extracted data from the included studies and assessed their quality using AGREE II (Appraisal of Guidelines for Research & Evaluation). The findings are presented narratively. Results: Forty-eight CMGs were included. They were produced in high- (42%, 20/48), upper-middle- (40%, 19/48), and lower-middle (8%, 4/48) income countries, or by international organisations (10%, 5/48). Most CMGs (81%, 39/48) were over 5 years old. Guidelines included treatment recommendations for children (75%, 36/48), pregnant women (54%, 26/48), people with immunosuppression (33%, 16/48), and older adults (29%, 14/48). Many CMGs were of low quality (median overall score: 3 out of 7 (range 1–7). All recommended oseltamivir; recommendations for other neuraminidase inhibitors and supportive care were limited and at times contradictory. Only 56% (27/48) and 27% (13/48) addressed oxygen and fluid therapy, respectively. Conclusions: Our data highlights the limited availability of up-to-date pandemic influenza CMGs globally. Of those identified, many were limited in scope and quality and several lacked recommendations for specific at-risk populations. Recommendations on supportive care, the mainstay of treatment, were limited and heterogeneous. The most recent guideline highlighted that the evidence-base to support antiviral treatment recommendations is still limited. There is an urgent need for trials into treatment and supportive care strategies including for different risk populations. New evidence should be incorporated into globally accessible guidelines, to benefit patient outcomes. A ‘living guideline’ framework is recommended and further research into guideline implementation in different resourced settings, particularly low- and middle-income countries

Preparing for pandemics: a systematic review of pandemic influenza clinical management guidelines

Background: The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and mortality by improving the quality of clinical decisions. This systematic review aims to evaluate the availability, inclusivity, and quality of pandemic influenza CMGs, to identify gaps that can be addressed to strengthen pandemic preparedness in this area. Methods: Ovid Medline, Ovid Embase, TRIP (Turning Research Into Practice), and Guideline Central were searched systematically from January 2008 to 23rd June 2022, complemented by a grey literature search till 16th June 2022. Pandemic influenza CMGs including supportive care or empirical treatment recommendations were included. Two reviewers independently extracted data from the included studies and assessed their quality using AGREE II (Appraisal of Guidelines for Research & Evaluation). The findings are presented narratively. Results: Forty-eight CMGs were included. They were produced in high- (42%, 20/48), upper-middle- (40%, 19/48), and lower-middle (8%, 4/48) income countries, or by international organisations (10%, 5/48). Most CMGs (81%, 39/48) were over 5 years old. Guidelines included treatment recommendations for children (75%, 36/48), pregnant women (54%, 26/48), people with immunosuppression (33%, 16/48), and older adults (29%, 14/48). Many CMGs were of low quality (median overall score: 3 out of 7 (range 1–7). All recommended oseltamivir; recommendations for other neuraminidase inhibitors and supportive care were limited and at times contradictory. Only 56% (27/48) and 27% (13/48) addressed oxygen and fluid therapy, respectively. Conclusions: Our data highlights the limited availability of up-to-date pandemic influenza CMGs globally. Of those identified, many were limited in scope and quality and several lacked recommendations for specific at-risk populations. Recommendations on supportive care, the mainstay of treatment, were limited and heterogeneous. The most recent guideline highlighted that the evidence-base to support antiviral treatment recommendations is still limited. There is an urgent need for trials into treatment and supportive care strategies including for different risk populations. New evidence should be incorporated into globally accessible guidelines, to benefit patient outcomes. A ‘living guideline’ framework is recommended and further research into guideline implementation in different resourced settings, particularly low- and middle-income countries

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Sista milen i svensk detaljhandel

Abstract Purpose: The purpose of this study is to explore last mile delivery practices among large and medium Swedish omni-channel (OC) retailers and e-tailers. Also, the study aims at analyzing what similarities and differences exist between the two types of retailers. Method: A literature review was carried out in order to gain more knowledge about the topic and develop a theoretical framework, used for analyzing data. Also, a quantitative study was conducted through electronic surveys (secondary data) and website observations (primary data). The 100 retailers were large and medium OC retailers and e-tailers and were selected based on a probability sample.  Findings: The study has shown that there are plenty of similarities and differences between the two kinds of retailers. Some of the delivery practices and options that OC retailers and e-tailers perform similarly are unattended HD (unattended home delivery), attached C&C (click and collect), drop shipping, free solitary C&C (click and collect). There are also differences between retailers when it comes to attended HD, time slot, eco delivery or LTL-Courier (Less Than Truckload-courier). E-tailers offer more competitive remote deliveries with more free remote delivery options. OC retailers leverage on both store network and remote delivery services. Thus, OC retailers can learn how to cope with e-commerce growth and adapt their delivery services as e-tailers do. Limitations: This study has a geographical focus on Swedish OC retailers and e-tailers. The data that was collected has been limited to the logistics variables: delivery mode, velocity, time slot, slot price differentiation, delivery fee, eco delivery, picking location, delivery area and transport service. Theoretical implications: This study is an important step towards contributing to academic theoretical literature regarding last mile delivery practices. Based on the previous frameworks, new logistical variables were added, such as more velocities, delivery fee, eco delivery and drop shipping. These contributions were helpful in the process of exploring characteristics about retailers and how they differ from each other. Managerial implications: This research is valuable for managers and retailers in order to find the best logistical strategy. It could be beneficial for OC retailers who face challenges that e-commerce brings and compete with e-tailers. Keywords: Last-mile delivery, Retailing, Omni-channel, E-tailers, E-commerce. Paper type: Research pape