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1.
Ann Pharmacother ; 57(12): 1415-1424, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37076990

RESUMO

OBJECTIVE: To provide nonobstetric practitioners with an overview of key concepts for the pregnant patient and review treatment of 3 common acute nonobstetric diseases encountered in the emergency department setting. DATA SOURCES: A literature search of PubMed was performed (1997-February 2023) using key search terms related to pregnancy, pain, urinary tract infection (UTI), venous thromboembolism (VTE), and anticoagulants. STUDY SELECTION AND DATA EXTRACTION: Relevant articles in English and humans were considered. DATA SYNTHESIS: When caring for a pregnant patient, it is important to utilize appropriate assessments, understand terms used in this population, and recognize how the physiological and pharmacokinetic changes that occur in pregnancy can influence medication use. Pain, UTIs, and VTE are common in this population. Acetaminophen is the most widely used medication for the management of pain during pregnancy and the drug of choice for mild pain in pregnancy not responsive to nonpharmacologic treatment. Pyelonephritis is the most common nonobstetric cause of hospitalization for pregnant patients. Antimicrobial treatment should consider maternal-fetal safety and local resistance patterns. Pregnant and postpartum patients have a 4- to 5-fold increased risk of developing a VTE compared with nonpregnant patients. Low-molecular-weight heparin is the preferred treatment. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Pregnant patients often seek acute care in the emergency department setting for nonobstetric needs. Pharmacists in this setting should understand appropriate assessment questions and terms used within this population, the basics of physiological and pharmacokinetic changes in pregnancy that can impact treatment, and which resources are best to utilize for drug information of the pregnant patient. CONCLUSION: Practitioners in the acute care setting commonly encounter pregnant patients seeking care for nonobstetric concerns. This article covers key pregnancy-related information for the nonobstetric practitioner and focuses on the management of acute pain, UTI, and VTE during pregnancy.


Assuntos
Infecções Urinárias , Tromboembolia Venosa , Gravidez , Feminino , Humanos , Tromboembolia Venosa/tratamento farmacológico , Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular , Infecções Urinárias/tratamento farmacológico , Dor/tratamento farmacológico , Serviço Hospitalar de Emergência
2.
Ann Pharmacother ; 55(4): 459-465, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32885981

RESUMO

BACKGROUND: Drug information resources are commonly used by health-care providers answering pregnancy-related medication questions. In 2015, the United States Food and Drug Administration approved a new pregnancy and lactation medication labeling content and format, removing the pregnancy category, and using a narrative. Despite labeling requirements changing, it is unknown if drug information resources updated monographs to reflect these changes. OBJECTIVE: The primary objective was to evaluate if commonly used drug information resources provide pregnancy information listed similar to the requirements of the Pregnancy and Lactation Labeling Rule (PLLR). Secondary analyses included evaluating the references and inclusion of the pregnancy category rating. METHODS: Pregnancy recommendations for 23 medications were evaluated in 9 drug information resources (Clinical Pharmacology, Drugs in Pregnancy and Lactation, Epocrates®, First Databank, LexiComp® Online, LexiComp® Online Pregnancy & Lactation, In-Depth, Medi-Span®, Micromedex®, and Multum®). The number of references per drug monograph and most recent reference publication year was obtained. RESULTS: LexiComp® Online Pregnancy & Lactation, In-Depth mimics the new PLLR structure and consistently had the highest number of and most recent references when the medication was included. Drugs in Pregnancy and Lactation was the next most similar in content with the PLLR and second in most references per monograph; however, the most recent reference was the textbook publication year. CONCLUSION AND RELEVANCE: LexiComp® Online Pregnancy & Lactation, In-Depth and Drugs in Pregnancy and Lactation provided pregnancy information in a format most similar to the PLLR. However, several drug information resources contained pregnancy categories ratings that were to be removed from medication labeling per the PLLR.


Assuntos
Rotulagem de Medicamentos/normas , Lactação/efeitos dos fármacos , Preparações Farmacêuticas/normas , Gravidez/efeitos dos fármacos , United States Food and Drug Administration/normas , Animais , Aleitamento Materno/tendências , Rotulagem de Medicamentos/tendências , Feminino , Humanos , Lactação/fisiologia , Gravidez/fisiologia , Estados Unidos/epidemiologia , United States Food and Drug Administration/tendências
3.
J Nanobiotechnology ; 19(1): 291, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579731

RESUMO

BACKGROUND: Treatment of bacterial biofilms are difficult and in many cases, expensive. Bacterial biofilms are naturally more resilient to antimicrobial agents than their free-living planktonic counterparts, rendering the community growth harder to control. The present work described the risks of long-term use of an important alternative antimicrobial, silver nanoparticles (NAg), for the first time, on the dominant mode of bacterial growth. RESULTS: NAg could inhibit the formation as well as eradicating an already grown biofilm of Pseudomonas aeruginosa, a pathogen notorious for its resilience to antibiotics. The biofilm-forming bacterium however, evolved a reduced sensitivity to the nanoparticle. Evidence suggests that survival is linked to the development of persister cells within the population. A similar adaptation was also seen upon prolonged exposures to ionic silver (Ag+). The persister population resumed normal growth after subsequent passage in the absence of silver, highlighting the potential risks of recurrent infections with long-term NAg (and Ag+) treatments of biofilm growth. The present study further observed a potential silver/antibiotic cross-resistance, whereby NAg (as well as Ag+) could not eradicate an already growing gentamicin-resistant P. aeruginosa biofilm. The phenomena is thought to result from the hindered biofilm penetration of the silver species. In contrast, both silver formulations inhibited biofilm formation of the resistant strain, presenting a promising avenue for the control of biofilm-forming antibiotic-resistant bacteria. CONCLUSION: The findings signify the importance to study the nanoparticle adaptation phenomena in the biofilm mode of bacterial growth, which are apparently unique to those already reported with the planktonic growth counterparts. This work sets the foundation for future studies in other globally significant bacterial pathogens when present as biofilms. Scientifically based strategies for management of pathogenic growth is necessary, particularly in this era of increasing antibiotic resistance.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Nanopartículas Metálicas/uso terapêutico , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Nanopartículas , Infecções por Pseudomonas , Pseudomonas aeruginosa/efeitos dos fármacos , Prata
4.
Int J Mol Sci ; 22(18)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34575891

RESUMO

Zinc pyrithione (ZnPT) is an anti-fungal drug delivered as a microparticle to skin epithelia. It is one of the most widely used ingredients worldwide in medicated shampoo for treating dandruff and seborrheic dermatitis (SD), a disorder with symptoms that include skin flaking, erythema and pruritus. SD is a multi-factorial disease driven by microbiol dysbiosis, primarily involving Malassezia yeast. Anti-fungal activity of ZnPT depends on the cutaneous availability of bioactive monomeric molecular species, occurring upon particle dissolution. The success of ZnPT as a topical therapeutic is underscored by the way it balances treatment efficacy with formulation safety. This review demonstrates how ZnPT achieves this balance, by integrating the current understanding of SD pathogenesis with an up-to-date analysis of ZnPT pharmacology, therapeutics and toxicology. ZnPT has anti-fungal activity with an average in vitro minimum inhibitory concentration of 10-15 ppm against the most abundant scalp skin Malassezia species (Malassezia globosa and Malassezia restrica). Efficacy is dependent on the targeted delivery of ZnPT to the skin sites where these yeasts reside, including the scalp surface and hair follicle infundibulum. Imaging and quantitative analysis tools have been fundamental for critically evaluating the therapeutic performance and safety of topical ZnPT formulations. Toxicologic investigations have focused on understanding the risk of local and systemic adverse effects following exposure from percutaneous penetration. Future research is expected to yield further advances in ZnPT formulations for SD and also include re-purposing towards a range of other dermatologic applications, which is likely to have significant clinical impact.


Assuntos
Antifúngicos/administração & dosagem , Epitélio/efeitos dos fármacos , Compostos Organometálicos/administração & dosagem , Piridinas/administração & dosagem , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Antifúngicos/química , Dermatite Seborreica/diagnóstico , Dermatite Seborreica/tratamento farmacológico , Dermatite Seborreica/etiologia , Disbiose , Epiderme/efeitos dos fármacos , Epitélio/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Imagem Óptica/métodos , Compostos Organometálicos/química , Piridinas/química , Pele/microbiologia , Absorção Cutânea , Análise Espectral
5.
Int J Mol Sci ; 22(22)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34830253

RESUMO

Zinc oxide nanoparticle (ZnO NP)-based sunscreens are generally considered safe because the ZnO NPs do not penetrate through the outermost layer of the skin, the stratum corneum (SC). However, cytotoxicity of zinc ions in the viable epidermis (VE) after dissolution from ZnO NP and penetration into the VE is ill-defined. We therefore quantified the relative concentrations of endogenous and exogenous Zn using a rare stable zinc-67 isotope (67Zn) ZnO NP sunscreen applied to excised human skin and the cytotoxicity of human keratinocytes (HaCaT) using multiphoton microscopy, zinc-selective fluorescent sensing, and a laser-ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) methodology. Multiphoton microscopy with second harmonic generation imaging showed that 67ZnO NPs were retained on the surface or within the superficial layers of the SC. Zn fluorescence sensing revealed higher levels of labile and intracellular zinc in both the SC and VE relative to untreated skin, confirming that dissolved zinc species permeated across the SC into the VE as ionic Zn and significantly not as ZnO NPs. Importantly, the LA-ICP-MS estimated exogenous 67Zn concentrations in the VE of 1.0 ± 0.3 µg/mL are much lower than that estimated for endogenous VE zinc of 4.3 ± 0.7 µg/mL. Furthermore, their combined total zinc concentrations in the VE are much lower than the exogenous zinc concentration of 21 to 31 µg/mL causing VE cytotoxicity, as defined by the half-maximal inhibitory concentration of exogenous 67Zn found in human keratinocytes (HaCaT). This speaks strongly for the safety of ZnO NP sunscreens applied to intact human skin and the associated recent US FDA guidance.


Assuntos
Epiderme/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Protetores Solares/farmacologia , Óxido de Zinco/farmacologia , Abdominoplastia/métodos , Administração Cutânea , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Epiderme/ultraestrutura , Feminino , Fluoresceínas/química , Corantes Fluorescentes/química , Humanos , Queratinócitos/citologia , Queratinócitos/ultraestrutura , Nanopartículas Metálicas/ultraestrutura , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Pessoa de Meia-Idade , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Quinolonas/química , Absorção Cutânea/fisiologia , Compostos de Tosil/química
6.
Ann Pharmacother ; 53(9): 899-904, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30907111

RESUMO

Background: Multiple resources aid the interprofessional health care team when recommending medications for lactating patients. Varying degrees of breastfeeding compatibility and safety are recommended in different resources. New Food and Drug Administration labeling for lactation is being phased in to provide more consistent language in safety recommendations. Objective: The objective of this study is to evaluate lactation recommendations for select medications from different drug information resources to determine the compatibility recommendations for lactating patients. Methods: The breastfeeding recommendations for 19 medications were analyzed in 10 drug information resources. Each drug was reviewed in each resource and the published recommendations evaluated. Results:Medications and Mothers' Milk 18th Edition and LactMed had the most medications listed as compatible with breastfeeding, with Lexicomp Online, Drugs in Pregnancy and Lactation Online, and Epocrates following. LactMed stands out from the group with an average of 15.1 references per medication and number of references ranging from 0 to 58. Date ranges of references used by select resources varied. References to support recommendations ranged from 1979 to 2018 for the select resources. Conclusion and Relevance: Variation continues to exist across resources with regard to recommendations for medication safety in lactation. LactMed represents the most up-to-date and comprehensive review of literature in this review. When making decisions regarding medication use during lactation, health care professionals should consider reviewing data behind the recommendations and consulting multiple resources.


Assuntos
Aleitamento Materno/tendências , Lactação/fisiologia , Valores de Referência , Feminino , Humanos , Gravidez
7.
Toxicol Appl Pharmacol ; 343: 40-47, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29471083

RESUMO

Zinc pyrithione is an active component incorporated in an extensive range of topically applied commercial products that are used worldwide. Despite its prevalence, no published study has investigated the penetration of zinc from the zinc pyrithione complex into human skin. Zinc is crucial for healthy skin function however an elevated concentration of labile zinc is toxic outside a narrow concentration range. Synchrotron X-ray fluorescence microscopy in conjunction with X-ray absorption near edge structure spectroscopy was used to map the deposition of zinc, quantitate the amount of zinc within the skin and to identify a change in the chemical form of zinc after application. This study has demonstrated a ~3.8 fold increase in zinc concentration within the viable epidermis (VE) after 24 h topical application of zinc pyrithione that increased significantly by ~250 fold after 48 h when compared to control skin. Confocal microscopy using a labile zinc specific dye, ZinPyr-1, showed that zinc pyrithione disrupted the skin cells zinc homeostasis and significantly increased the intracellular zinc concentration leading to cell toxicity. Overall, this study demonstrates that topical application of zinc pyrithione formulations leads to an increase in zinc penetration in human skin, consequently, raising concerns for potential localised toxicity to occur.


Assuntos
Epiderme/diagnóstico por imagem , Epiderme/metabolismo , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/metabolismo , Piridinas/administração & dosagem , Piridinas/metabolismo , Absorção Cutânea/fisiologia , Administração Tópica , Adulto , Linhagem Celular , Epiderme/efeitos dos fármacos , Feminino , Humanos , Técnicas de Cultura de Órgãos , Absorção Cutânea/efeitos dos fármacos , Espectroscopia por Absorção de Raios X/métodos , Zinco/administração & dosagem , Zinco/metabolismo , Óxido de Zinco/administração & dosagem , Óxido de Zinco/metabolismo
8.
Int J Legal Med ; 132(3): 691-701, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29177703

RESUMO

DNA quantification is a vital step in forensic DNA analysis to determine the optimal input amount for DNA typing. A quantitative real-time polymerase chain reaction (qPCR) assay that can predict DNA degradation or inhibitors present in the sample prior to DNA amplification could aid forensic laboratories in creating a more streamlined and efficient workflow. This study compares the results from four commercial qPCR kits: (1) Investigator® Quantiplex® Pro Kit, (2) Quantifiler® Trio DNA Quantification Kit, (3) PowerQuant® System, and (4) InnoQuant® HY with high molecular weight DNA, low template samples, degraded samples, and DNA spiked with various inhibitors.The results of this study indicate that all kits were comparable in accurately predicting quantities of high quality DNA down to the sub-picogram level. However, the InnoQuant(R) HY kit showed the highest precision across the DNA concentration range tested in this study. In addition, all kits performed similarly with low concentrations of forensically relevant PCR inhibitors. However, in general, the Investigator® Quantiplex® Pro Kit was the most tolerant kit to inhibitors and provided the most accurate quantification results with higher concentrations of inhibitors (except with salt). PowerQuant® and InnoQuant® HY were the most sensitive to inhibitors, but they did indicate significant levels of PCR inhibition. When quantifying degraded samples, each kit provided different degradation indices (DI), with Investigator® Quantiplex® Pro indicating the largest DI and Quantifiler® Trio indicating the smallest DI. When the qPCR kits were paired with their respective STR kit to genotype highly degraded samples, the Investigator® 24plex QS and GlobalFiler® kits generated more complete profiles when the small target concentrations were used for calculating input amount.


Assuntos
Degradação Necrótica do DNA , Impressões Digitais de DNA , Reação em Cadeia da Polimerase em Tempo Real/instrumentação , DNA/análise , Humanos , Repetições de Microssatélites
9.
Mikrochim Acta ; 185(2): 128, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29594671

RESUMO

The authors describe the synthesis of water-soluble and fluorescent graphene oxide quantum dots via acid exfoliation of graphite nanoparticles. The resultant graphene oxide quantum dots (GoQDs) were then modified with folic acid. Folic acid receptors are overexpressed in cancer cells and hence can bind to functionalized graphene oxide quantum dots. On excitation at 305 nm, the GoQDs display green fluorescence with a peak wavelength at ~520 nm. The modified GoQDs are non-toxic to macrophage cells even after prolonged exposure and high concentrations. Fluorescence lifetime imaging and multiphoton microscopy was used (in combination) to image HeCaT cells exposed to GoQDs, resulting in a superior method for bioimaging. Graphical abstract Schematic representation of graphene oxide quantum dots, folic acid modified graphene oxide quantum dots (red), and the use of fluorescence lifetime to discriminate against green auto-fluorescence of HeCaT cells.


Assuntos
Ácido Fólico/química , Grafite/química , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Pontos Quânticos/química , Linhagem Celular Tumoral , Receptores de Folato com Âncoras de GPI/análise , Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/metabolismo , Humanos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Neoplasias/patologia
10.
J Pediatr Hematol Oncol ; 39(7): e403-e405, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28452855

RESUMO

Hemophilia A is an X-linked, recessive disorder resulting from mutations in the f8 gene. Here we report the rare case of a female compound heterozygote with mild factor VIII deficiency (fVIII:C 9%) and moderate phenotype. On investigation she was confirmed to have normal Von Willebrand factor studies with a 46XY genotype. Further genetic testing revealed 3 mutations in the f8 gene: 1 novel missense mutation (c.6142T>G), 1 novel in-frame deletion (c.1281_1292del), and another missense mutation of unclear significance (c.3780C>G). Both parents had normal coagulation profiles; however, the 2 novel mutations were present in the patient's mother and the known missense mutation was present in her father. This unusual case demonstrates the utility in genetic analysis for f8 gene mutational analysis and suggests a compound effect of the 3 identified mutations as a cause for factor deficiency.


Assuntos
Fator VIII/genética , Hemofilia A/genética , Mutação de Sentido Incorreto , Feminino , Humanos , Linhagem , Fenótipo , Deleção de Sequência
11.
Adv Neonatal Care ; 16(4): 264-72, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27391563

RESUMO

BACKGROUND: Very low birth-weight (<1500 g) infants are vulnerable to their environment during the first hour after birth. We designed an evidence-based golden hour protocol (GHP) with a goal to stabilize and perform admission procedures within 1 hour of birth at a level IIIB neonatal intensive care unit (NICU). PURPOSE: The aim of this quality improvement project was to ascertain whether an evidence-based GHP would improve care efficiency and short-term outcomes. METHODS: Rapid cycles of change using Plan Do Study Act were utilized to document progress and gain knowledge during the quality improvement project. Measures were plotted with statistical process control methods (SPC), which analyzed improvement over time. RESULTS: Both admission temperature and glucose-level means were within reference range throughout the project and predicted a stable process. We observed significantly decreased time to initiation of intravenous fluids and antibiotics. An upward trend of surfactant administration within the first 2 hours of life was also observed. IMPLICATIONS FOR PRACTICE: The use of a GHP provided an organized approach to admission procedures and care. By using a checklist and recording intervention times, NICU caregivers were more aware of time management for each intervention and were able to decrease time to initiation of intravenous fluids and antibiotics. IMPLICATIONS FOR RESEARCH: Future research should focus on establishing normal blood pressure ranges and safe pain management during the "golden hour" and beyond. Future quality improvement should focus on improving subsequent temperature and blood glucose levels after admission umbilical artery and venous catheter placement.


Assuntos
Cuidado do Lactente/métodos , Recém-Nascido de muito Baixo Peso , Terapia Intensiva Neonatal/métodos , Equipe de Assistência ao Paciente/organização & administração , Melhoria de Qualidade , Tempo para o Tratamento , Antibacterianos/administração & dosagem , Glicemia , Temperatura Corporal , Protocolos Clínicos , Hidratação , Humanos , Recém-Nascido , Surfactantes Pulmonares/administração & dosagem
13.
J Pediatr Pharmacol Ther ; 29(2): 100-106, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38596421

RESUMO

The concept of the second victim, described as the sense of victimization of health care professionals following the exposure to a traumatic, unanticipated medical error, was first introduced in 2000 by Albert W. Wu. Since then, the concept has gained immense traction and inspired the generation of assistance programs for second victims. With most second victim occurrences resulting from medication errors, pediatric pharmacists are at a high risk of experiencing second victim phenomenon. Second victims may experience both psychological and physical symptoms of distress often akin to post-traumatic stress disorder. Typical trajectories for second victims, as well as typical support needs, have been previously described, with several organizations responding by creating formal programs designed to support their staff in the events of traumatic workplace experiences. Most support programs involve peer-to-peer support, group sessions, and programs designed to increase coping skills. Additional resources are available for health care workers who do not have formalized support programs at their institution, although these are limited. Despite these resources, institutions across the country have room for additional growth in their support of employees who become second victims to tragedy.

14.
Artigo em Inglês | MEDLINE | ID: mdl-37107736

RESUMO

Paternal mental health continues to be a health concern in the UK. Paternal leave entitlement and workplace cultures have failed to support fathers in navigating the complexity of fatherhood, which has an impact on fathers' wellbeing. Interviewing twenty fathers in the York area, this study seeks to explore the impact of parental leave entitlements and workplace cultures on fathers' mental health. The findings demonstrate that the influence of gendered norms and hegemonic masculinity perceptions are ingrained in the current leave entitlement and workplace cultures. While fathers are entitled to take leave, the leave is significantly insufficient to allow them to forge a meaningful bond with a newborn or adapt to the change in routine brought about by the birth of a baby. Furthermore, workplace cultures fail to recognise the responsibilities that come with fatherhood and provide insufficient support for fathers. The COVID-19 lockdown presented fathers with a unique opportunity to be available and take on more family responsibilities. Fathers felt they did not have to navigate gendered and hegemonic perceptions to spend more time with the family. This paper challenges structural and cultural barriers that prevent fathers from taking leave and impacting negatively on fathers' mental health. The paper suggests a review of the current paternal leave entitlement and cultural change in the workplace.


Assuntos
COVID-19 , Saúde Mental , Masculino , Lactente , Recém-Nascido , Humanos , Controle de Doenças Transmissíveis , Pai/psicologia , Local de Trabalho
15.
Eur J Pharm Biopharm ; 185: 148-164, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36842718

RESUMO

Seborrheic dermatitis (SD) is a common dermatological disorder with symptoms that include skin flaking, erythema and pruritus. This review discusses the topical products available for treating SD, which target several aspects of disease pathobiology, including cutaneous microbial dysbiosis (driven by Malassezia yeast), inflammation, sebum production and skin barrier disruption. Among the various treatments available, zinc pyrithione (ZnPT) based products that exhibit anti-fungal action are the market leaders. A skin compartment approach is presented here for combining ZnPT exposure information with threshold levels for anti-fungal efficacy and toxicity, overall providing a comprehensive picture of ZnPT therapeutics and safety. While Malassezia yeast on the surface are effectively targeted, yeast residing beyond the superficial follicle may not receive adequate ZnPT for anti-fungal effect forming the basis for skin re-colonisation. Levels entering systemic circulation from topical delivery are well below toxic thresholds, however the elevated zinc levels within the viable epidermis warrants further investigation. Strategies to improve formulation design can be broadly classified as influencing 1) topical delivery, 2) therapeutic bioactivity, 3) skin mildness, and 4) sensory attributes. Successful SD treatment ultimately requires formulations that can balance efficacy, safety, and consumer appeal.


Assuntos
Dermatite Seborreica , Malassezia , Humanos , Dermatite Seborreica/tratamento farmacológico , Dermatite Seborreica/microbiologia , Saccharomyces cerevisiae , Pele , Epiderme , Sebo
16.
Pharmaceutics ; 15(11)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-38004557

RESUMO

Non-melanoma skin cancer (NMSC) is the most prevalent malignancy worldwide, with approximately 6.3 million new cases worldwide in 2019. One of the key management strategies for NMSC is a topical treatment usually utilised for localised and early-stage disease owing to its non-invasive nature. However, the efficacy of topical agents is often hindered by poor drug penetration and patient adherence. Therefore, various research groups have employed advanced drug delivery systems, including topical patches to overcome the problem of conventional topical treatments. This review begins with an overview of NMSC as well as the current landscape of topical treatments for NMSC, specifically focusing on the emerging technology of topical patches. A detailed discussion of their potential to overcome the limitations of existing therapies will then follow. Most importantly, to the best of our knowledge, this work unprecedentedly combines and discusses all the current advancements in innovative topical patches for the treatment of NMSC. In addition to this, the authors present our insights into the key considerations and emerging trends in the construction of these advanced topical patches. This review is meant for researchers and clinicians to consider utilising advanced topical patch systems in research and clinical trials toward localised interventions of NMSC.

17.
J Forensic Sci ; 68(2): 596-607, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36725687

RESUMO

Formalin-fixed tissues provide the medical and forensic communities with alternative and often last resort sources of DNA for identification or diagnostic purposes. The DNA in these samples can be highly degraded and chemically damaged, making downstream genotyping using short tandem repeats (STRs) challenging. Therefore, the use of alternative genetic markers, methods that pre-amplify the low amount of good quality DNA present, or methods that repair the damaged DNA template may provide more probative genetic information. This study investigated whether whole genome amplification (WGA) and DNA repair could improve STR typing of formaldehyde-damaged (FD) tissues from embalmed cadavers. Additionally, comparative genotyping success using bi-allelic markers, including INDELs and SNPs, was explored. Calculated random match probabilities (RMPs) using traditional STRs, INDEL markers, and two next generation sequencing (NGS) panels were compared across all samples. Overall, results showed that neither WGA nor DNA repair substantially improved STR success rates from formalin-fixed tissue samples. However, when DNA from FD samples was genotyped using INDEL and SNP-based panels, the RMP of each sample was markedly lower than the RMPs calculated from partial STR profiles. Therefore, the results of this study suggest that rather than attempting to improve the quantity and quality of severely damaged and degraded DNA prior to STR typing, a more productive approach may be to target smaller amplicons to provide more discriminatory DNA identifications. Furthermore, an NGS panel with less loci may yield better results when examining FD samples, due to more optimized chemistries that result in greater allelic balance and amplicon coverage.


Assuntos
Impressões Digitais de DNA , Antropologia Forense , Humanos , Impressões Digitais de DNA/métodos , Formaldeído , Genótipo , DNA/análise , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único
18.
Int J Nanomedicine ; 18: 1007-1029, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36855538

RESUMO

Background: Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara®) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option. Methods: Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach. The optimized formulation was then incorporated into a matrix-type topical patch as an alternative dosage form for topical application and evaluated for IMQ deposition across different skin layers in comparison to the performance of the commercial product. Additionally, our work also attempted to highlight the possibility of implementing environment-friendly practices in our IMQ-NLCs formulation development by reviewing our analytical methods and experimental designs and reducing energy and solvent consumption where possible. Results: In this study, stearyl alcohol, oleic acid, Tween® 80 (polysorbate 80), and Gelucire® 50/13 (Stearoyl polyoxyl-32 glycerides) were selected for formulation development. The formulation was optimized using a 2k factorial design and a central composite design. The optimized formulation achieved the average particle size, polydispersity index, and zeta potential of 75.6 nm, 0.235, and - 30.9 mV, respectively. Subsequently, a matrix-type patch containing IMQ-NLCs was developed and achieved a statistically significant improvement in IMQ deposition in the deeper skin layers. The IMQ deposition from the patch into the dermis layer and receptor chamber was 3.3 ± 0.9 µg/cm2 and 12.3 ± 2.2 µg/cm2, while the commercial cream only deposited 1.0 ± 0.8 µg/cm2 and 1.5 ± 0.5 µg/cm2 of IMQ, respectively. Conclusion: In summary, IMQ-NLC-loaded patches represent great potential as a topical treatment option for skin cancer with improved patient compliance.


Assuntos
Nanoestruturas , Pele , Humanos , Imiquimode , Alimentos , Glicerídeos
20.
J Forensic Sci ; 67(4): 1336-1347, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35442526

RESUMO

Crime laboratories have been faced with large casework backlogs due to lengthy processing times, limited resources and scientists, and rising crime rates. Evidence related to sexual assault crimes, specifically sexual assault kits (SAKs), heavily contribute to the reported backlogs. Although more sensitive, faster chemistries and automated techniques have been implemented over the years, the traditional STR workflow remains relatively unchanged. Enhanced workflows such as direct PCR and Rapid DNA have the potential to streamline the processing of forensic evidence items including those commonly submitted in SAKs, but the FBI QAS guidelines restrict CODIS-approved labs from implementing these methods for forensic samples. Recent studies have shown decreased turnaround times and improved or comparable profiling success with both approaches. However, review of the literature shows a lack of in-depth research comparing traditional DNA workflows to faster and more sensitive direct PCR and/or Rapid DNA approaches for evidentiary samples, especially for SAKs. By providing the forensic science and criminal justice communities with the strengths and limitations of direct PCR and Rapid DNA methods, stakeholders and policy makers may be better informed.


Assuntos
Vítimas de Crime , Delitos Sexuais , DNA/análise , Impressões Digitais de DNA , Humanos , Aplicação da Lei/métodos , Reação em Cadeia da Polimerase , Manejo de Espécimes
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