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Sulfonamides have gained prominence as versatile agents in cancer therapy, effectively targeting a spectrum of cancer-associated enzymes. This review provides an extensive exploration of their multifaceted roles in cancer biology. Sulfonamides exhibit adaptability by acting as tyrosine kinase inhibitors, disrupting pivotal signaling pathways in cancer progression. Moreover, they disrupt pH regulation mechanisms in cancer cells as carbonic anhydrase inhibitors, inhibiting growth, and survival. Sulfonamides also serve as aromatase inhibitors, interfering with estrogen synthesis in hormone-driven cancers. Inhibition of matrix metalloproteinases presents an opportunity to impede cancer cell invasion and metastasis. Additionally, their emerging role as histone deacetylase inhibitors offers promising prospects in epigenetic-based cancer therapies. These diverse roles underscore sulfonamides as invaluable tools for innovative anti-cancer treatments, warranting further exploration for enhanced clinical applications and patient outcomes.
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Antineoplásicos , Neoplasias , Sulfonamidas , Humanos , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Animais , Relação Estrutura-AtividadeRESUMO
Joining the global effort to eradicate tuberculosis, one of the deadliest infectious killers in the world, we disclose in this paper the design and synthesis of new indolinone-tethered benzothiophene hybrids 6a-i and 7a-i as potential anti-tubercular agents. The MICs were determined in vitro for the synthesized compounds against the sensitive M. tuberculosis strain ATCC 25177. Potent compounds 6b, 6d, 6f, 6h, 7a, 7b, 7d, 7f, 7h and 7i were furtherly assessed versus resistant MDR-TB and XDR-TB. Structure activity relationship investigation of the synthesized compounds was illustrated, accordingly. Superlative potency was unveiled for compound 6h (MIC = 0.48, 1.95 and 7.81 µg/mL for ATCC 25177 sensitive TB strain, resistant MDR-TB and XDR-TB, respectively). Moreover, validated in vivo pharmacokinetic study was performed for the most potent derivative 6h revealing superior pharmacokinetic profile over the reference drug. For further exploration of the anti-tubercular mechanism of action, molecular docking was carried out for the former compound in DprE1 active site as one of the important biological targets of TB. The binding mode and the docking score uncovered exceptional binding when compared to the co-crystallized ligand suggesting that it maybe the underlying target for its outstanding anti-tubercular potency.
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Tuberculose Extensivamente Resistente a Medicamentos , Mycobacterium tuberculosis , Tiofenos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/química , Simulação de Acoplamento Molecular , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Relação Estrutura-Atividade , Testes de Sensibilidade MicrobianaRESUMO
ABSTRACT: This article describes an exemplary collaboration in which a librarian was fully embedded in beginner undergraduate nursing courses in a baccalaureate nursing program. The goal was to increase academic help-seeking behaviors and information literacy skills. Students benefited from the intervention and increasingly demonstrated the use of better sources for their evidence-based practice assignments. Library tutorials were permanently integrated into the courses. A collaborative approach to designing research assignments allowed the librarian and nursing faculty to lay a foundation of information literacy in the nursing program and encourage academic help-seeking behaviors.
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AIM: To establish the responses to the Sinopharm HB02 COVID-19 vaccination in the dialysis population, which are not well established. We examined the humoral responses to the Sinopharm COVID vaccine in haemodialysis patients. METHODS: Standard vaccinations (two doses at interval of ~21 days) were given to all consenting haemodialysis patients on dialysis (n = 1296). We measured the antibody responses at 14-21 days after the second vaccine to define the development of anti-spike antibodies >15 AU/ml after vaccination and observed the clinical effects of vaccination. RESULTS: Vaccination was very well tolerated with few side-effects. In those who consented to antibody measurements, (n = 446) baseline sampling showed 77 had positive antibodies, yet received full vaccination without any apparent adverse events. Positive anti-spike antibodies developed in 50% of the 270 baseline negative patients who had full sampling, compared with 78.1% in the general population. COVID infection continues to occur in both vaccinated and unvaccinated individuals, but in the whole group vaccination appears to have been associated with a reduction in the case fatality rate. CONCLUSION: The humoral immune responses to standard HB02 vaccination schedules are attenuated in a haemodialysis cohort, but likely the vaccine saves lives. We suggest that an enhanced HB02 vaccination course or antibody checking may be prudent to protect this vulnerable group of patients. We suggest a booster dose of this vaccine at 3 months should be given to all dialysis patients, on the grounds that it is well tolerated even in those with good antibody levels and there may be a survival advantage.
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Formação de Anticorpos , Vacinas contra COVID-19 , COVID-19 , Imunogenicidade da Vacina/imunologia , Falência Renal Crônica , Diálise Renal , SARS-CoV-2/imunologia , Formação de Anticorpos/efeitos dos fármacos , Formação de Anticorpos/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/estatística & dados numéricos , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/imunologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Resultado do Tratamento , Emirados Árabes Unidos/epidemiologia , Vacinação/métodos , Vacinação/estatística & dados numéricos , Vacinas de Produtos InativadosRESUMO
A sensitive and selective UPLC-MS/MS method was developed for the synchronized determination of four drugs used in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, azithromycin, apixaban, dexamethasone, and favipiravir in rat plasma. using a Poroshell 120 EC-C18 column (50 mm × 4.6 mm, 2.7 m) with a high-resolution ESI tandem mass spectrometer detection with multiple reaction monitoring. We used an Agilent Poroshell column, which is characterized by a stationary phase based on non-porous core particles. With a remarkable improvement in the number of theoretical plates and low column backpressure. In addition, the developed method was employed in studying the potential food-drug interaction of grapefruit juice (GFJ) with the selected drugs which affects their pharmacokinetics in rats. The LC-MS/MS operated in positive and negative ionization mode using two internal standards: moxifloxacin and chlorthalidone, respectively. Liquid- liquid extraction of the cited drugs from rat plasma was accomplished using diethyl ether: dichloromethane (70:30, v/v). The analytes were separated using methanol: 0.1 % formic acid in water (95: 5, v/v) as a mobile phase in isocratic mode of elution pumped at a flow rate of 0.3 mL/min. A detailed validation of the bio-analytical method was performed in accordance with US-FDA and EMA guidelines. Concerning the in vivo pharmacokinetic study, the statistical significance between the results of the test groups receiving GFJ along with the cited drugs and the control group was assessed demonstrating that GFJ increased the plasma concentration of azithromycin, apixaban, and dexamethasone. Accordingly, this food-drug interaction requires cautious ingestion of GFJ in patients using (SARS-CoV-2) medications as it can produce negative effects in the safety of the drug therapy. A potential drug-drug interaction is also suggested between those medications requiring a suitable dose adjustment.
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Nonsteroidal anti-inflammatory drugs represent one of the most popularly used classes of drugs. However, their long-term administration is associated with various side effects including gastrointestinal ulceration. One of the major reasons of NSAIDs ulcerogenicity is direct damage of the epithelial lining cells by the acidic moieties present in many drugs. Another drawback for this acidic group is its rapid metabolism and clearance through Phase II conjugation. Three series of thiophene and thienopyrimidine derivatives were designed and synthesized as nonacidic anti-inflammatory agents. In vivo testing of their analgesic activity indicated that compounds 2b and 7a-d showed higher PI values than that of the positive control drugs, indomethacin and celecoxib. The latter compounds 2b and 7a-d were subjected to further anti-inflammatory activity testing where they showed comparable percentage edema inhibition to that of indomethacin and celecoxib. Compounds 2b, 7a, 7c, and 7d inhibited PGE2 synthesis by 61.10%-74.54% (71.47% for indomethacin, and 80.11% for celecoxib). The same compounds inhibited the expression of rat mPGES-1 and cPGES3 by 74%-83% (77% for indomethacin, and 82% for celecoxib) and 48%-70% (62% for indomethacin, and 70% for celecoxib), respectively. The stability of the most active compound 2b in Nonenzymatic gastrointestinal fluids and in human plasma was tested. Additionally, studying the metabolic stability of compound 2b in S9 rat liver fraction showed that it displayed a slow in vitro clearance with half-life time 1.5-fold longer than indomethacin. The metabolites of 2b were predicted via UPLC-MS/MS. In silico ADMET profiling study was also included.
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Analgésicos , Tiofenos , Animais , Humanos , Ratos , Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Celecoxib/uso terapêutico , Cromatografia Líquida , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Edema/tratamento farmacológico , Indometacina/farmacologia , Espectrometria de Massas em Tandem , Tiofenos/farmacologiaRESUMO
OBJECTIVES: The aims of the study were to evaluate the effects of two types of intrauterine contraceptive device (IUCD) on uterine artery Doppler indices. METHODS: A multicentre randomised clinical trial was conducted between November 2019 and August 2020. Sixty-six multiparous women aged 18-45 years seeking intrauterine contraception were randomly assigned to receive either the levonorgestrel-releasing intrauterine system (LNG-IUS) or the copper intrauterine device (Cu-IUD). Each group comprised 33 participants. Primary outcome measures were menstrual changes and changes in uterine artery Doppler indices 3 and 6 months after IUCD insertion. Secondary outcomes measures were the relation between Doppler indices and menstrual changes, adverse effects of the assigned contraceptive method and user acceptability of the method. RESULTS: Uterine artery pulsatility index (PI) and resistance index (RI) were significantly higher among women in the LNG-IUS group (p < .001 at 6 months). Whereas the number of women reporting heavy menstrual bleeding decreased at 3 and 6 months in the LNG-IUS group it significantly increased in the Cu-IUD group (p < .001 at 6 months). Multiple logistic regression analysis of participant characteristics and occurrence of heavy menstrual bleeding revealed a significant association with uterine artery RI (p < .01) and the type of IUCD (p < .001). CONCLUSION: IUCDs are associated with Doppler changes that may be associated with their reported side effects.
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Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos Medicados , Artéria Uterina , Adolescente , Adulto , Anticoncepcionais Femininos/efeitos adversos , Feminino , Humanos , Dispositivos Intrauterinos de Cobre/efeitos adversos , Dispositivos Intrauterinos Medicados/efeitos adversos , Levanogestrel/efeitos adversos , Pessoa de Meia-Idade , Ultrassonografia Doppler , Artéria Uterina/diagnóstico por imagem , Adulto JovemRESUMO
In the current coronavirus disease 2019 (COVID-19) pandemic there is a mass screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) happening around the world due to the extensive spread of the infections. There is a high demand for rapid diagnostic tests to expedite the identification of cases and to facilitate early isolation and control spread. Hence this study evaluates six different rapid nucleic acid detection assays that are commercially available for SARS-CoV-2 virus detection. Nasopharyngeal samples were collected from 4981 participants and were tested for the SARS-CoV-2 virus by the gold standard real-time reverse-transcription polymerase chain reaction (RT-PCR) method and with one of these six rapid methods of detection. Evaluation of the rapid nucleic acid detection assays was done by comparing the results of these rapid methods with the gold standard RT-qPCR results for SARS-COV-2 detection. AQ-TOP had the highest sensitivity (98%) and a strong kappa value of 0.943 followed by Genechecker and Abbot ID NOW. The POCKIT (ii RT-PCR) assay had the highest test accuracy of 99.29% followed by Genechecker and Cobas Liat. Atila iAMP showed the highest percentage of invalid reports (35.5%) followed by AQ-TOP with 6% and POCKIT with 3.7% of invalid reports. Genechecker system, Abbott ID NOW, and Cobas Liat were found to have the best performance and agreement when compared with the standard RT-PCR for COVID-19 detection. With further research, these rapid tests have the potential to be employed in large-scale screening of COVID-19.
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Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/isolamento & purificação , Teste de Ácido Nucleico para COVID-19/instrumentação , Teste de Ácido Nucleico para COVID-19/normas , Humanos , Nasofaringe/virologia , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/genética , Sensibilidade e Especificidade , Emirados Árabes UnidosRESUMO
BACKGROUND: The current pandemic of the SARS-CoV-2 virus, widely known as COVID-19, has affected millions of people around the world. The World Health Organization (WHO) has recommended vigorous testing to differentiate SARS-CoV-2 from other respiratory infections to aid in guiding appropriate care and management. Situations like this have demanded robust testing strategies and pooled testing of samples for SARS-CoV-2 virus has provided the solution to mass screening of people for COVID-19. A pooled testing strategy can be very effective in testing when resources are limited, yet it comes with its own limitations. These benefits and limitations need critical consideration when it comes to testing highly infectious diseases like COVID-19. METHODS: This study evaluated the pooled testing of nasopharyngeal swabs for SARS-COV-2 by comparing the sensitivity of individual sample testing with 4-and 8-pool sample testing. Median cycle threshold (Ct) values were compared, and the precision of pooled testing was assessed through an inter- and intra-assay of pooled samples. Coefficient of variance was calculated for inter- and intra-assay variability. RESULTS: The sensitivity becomes considerably lower when the samples are pooled. There is a high percentage of false negative reports with larger sample pool size and when the patient viral load is low or weak positive samples. High variability was seen in the intra- and inter-assay, especially among weak positive samples and when more number of samples are pooled together. CONCLUSION: As COVID - 19 infection numbers and need for testing remain high, we must meticulously evaluate the testing strategy for each country depending on its testing capacity, infrastructure, economic strength, and need to determine the optimal balance on the cost-effective strategy of resource saving and risk/ cost of missing positive patients.
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Teste para COVID-19/métodos , COVID-19/diagnóstico , Programas de Rastreamento/métodos , Técnicas de Laboratório Clínico , Humanos , Pandemias , SARS-CoV-2 , Sensibilidade e Especificidade , Carga ViralRESUMO
BACKGROUND: The safety of combining buprenorphine with a benzodiazepine or barbiturate in the treatment of concurrent alcohol and opioid withdrawal has not been well established. In this study we examine a cohort of patients treated with buprenorphine and phenobarbital or benzodiazepines for co-occurring opioid and alcohol withdrawal. METHODS: This is a retrospective cohort study of ED patients treated for opioid and alcohol withdrawal from January through December 2018. The primary outcome was unexpected airway intervention, or the administration of naloxone for respiratory depression. RESULTS: There were 16 patients treated for opioid and alcohol withdrawal. The mean age was 44.3 (standard deviation [SD] 13.1), 12 (75.0%) were male, and 8 (50.0%) of the patients were admitted to the hospital. For opioid withdrawal, six patients received intravenous buprenorphine, with doses between 0.3 mg to 1.8 mg; 12 patients received sublingual buprenorphine, with doses between 4 mg to 32 mg. For alcohol withdrawal, 10 patients received lorazepam with doses between 1 mg and 8 mg; 10 patients received phenobarbital with doses between 260 mg to 1040 mg. There were no unexpected airway interventions related to medications used for opioid or alcohol withdrawal. One patient with severe pneumonia was an expected intubation for respiratory failure. CONCLUSIONS: We describe a cohort of patients treated for opioid and alcohol withdrawal in the ED. There were no serious adverse events related to the medications used to treat opioid or alcohol withdrawal. Further work should assess optimal use of medical therapy for opioid and alcohol withdrawal and the transition to maintenance treatment for substance use disorders.
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Transtornos Relacionados ao Uso de Álcool/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adulto , Idoso , Buprenorfina/administração & dosagem , Serviço Hospitalar de Emergência , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Lorazepam/administração & dosagem , Masculino , Pessoa de Meia-Idade , Antagonistas de Entorpecentes/administração & dosagem , Fenobarbital/administração & dosagem , Estudos RetrospectivosRESUMO
An accurate and sensitive UPLC-MS/MS method was developed and validated for the simultaneous estimation of the newly developed combination of sacubitril and valsartan and the co-administered drugs nebivolol, chlorthalidone and esomeprazole in human plasma. Solid-phase extraction was conducted for the purification and extraction of the drugs from human plasma. Chromatographic separation was carried out on an Agilent SB-C18 (1.8 µm, 2.1 × 50 mm) column using losartan as internal standard. Isocratic elution was applied using acetonitrile-0.1% formic acid in water (85: 15, v/v) as mobile phase. Detection was carried out using a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring, at positive mode at m/z 412.23 â 266.19 for sacubitril, m/z 436.29 â 235.19 for valsartan, m/z 405.8 â 150.98 for nebivolol, m/z 346.09 â 198 for esomeprazole and a selected combination of two fragments m/z 423.19 â 207.14 and 423.19 â 192.2 for losartan (internal standard), and in negative ionization mode at m/z 337.02 â 190.12 for chlorthalidone. The method was linear over the concentration ranges 30-2,000 ng/ml for sacubitril, 70-2,000 ng/ml for valsartan, esomeprazole and chlorthalidone and 70-5,000 pg/ml for nebivolol. The developed method is sensitive and selective and could be applied for dose adjustment, bioavailability and drug-drug interaction studies.
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Aminobutiratos/sangue , Compostos de Bifenilo/sangue , Cromatografia Líquida de Alta Pressão/métodos , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Valsartana/sangue , Aminobutiratos/administração & dosagem , Aminobutiratos/isolamento & purificação , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/isolamento & purificação , Clortalidona/administração & dosagem , Clortalidona/sangue , Clortalidona/isolamento & purificação , Combinação de Medicamentos , Estabilidade de Medicamentos , Esomeprazol/administração & dosagem , Esomeprazol/sangue , Esomeprazol/isolamento & purificação , Humanos , Limite de Detecção , Modelos Lineares , Nebivolol/administração & dosagem , Nebivolol/sangue , Nebivolol/isolamento & purificação , Reprodutibilidade dos Testes , Valsartana/administração & dosagem , Valsartana/isolamento & purificaçãoRESUMO
Importance: Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. Objective: To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. Design, Setting, and Participants: Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. Interventions: Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)-only control (n = 13 458); they received 2 intramuscular injections 21 days apart. Main Outcomes and Measures: The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. Results: Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase-polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]). Conclusions and Relevance: In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending. Trial Registration: ClinicalTrials.gov Identifier: NCT04510207; Chinese Clinical Trial Registry: ChiCTR2000034780.
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Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Imunogenicidade da Vacina , Adulto , COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Conjuntos de Dados como Assunto , Método Duplo-Cego , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Oriente Médio , Vacinas de Produtos Inativados/imunologiaRESUMO
The ultrasound-guided transversus abdominis plane (TAP) block or TAP block is a well-established regional anesthetic block used by anesthesiologists for peri-operative pain control of the anterior abdominal wall. Multiple studies have demonstrated its utility to control pain for a range of procedures from inguinal hernia repair, laparoscopic cholecystectomies to cesarean sections [1-3]. There are no cases describing the efficacy of the ultrasound-guided TAP block in the emergency department as a part of a multimodal pain pathway for patients diagnosed with acute appendicitis. We developed a pain protocol in conjunction with our surgical colleagues that incorporates the TAP block to reduce opioid use, and better treat acute pain in patients with acute appendicitis diagnosed in the emergency department. We successfully performed ultrasound-guided TAP blocks in 3 patients with computed tomography confirmed appendicitis, reducing pain and need for further opioid use. This interdepartmental collaborative pathway could be an ideal anesthetic plan for patients diagnosed in the emergency department with acute appendicitis.
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Apendicite/cirurgia , Bloqueio Nervoso/métodos , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle , Músculos Abdominais/diagnóstico por imagem , Adulto , Analgésicos não Narcóticos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Anestésicos Locais/administração & dosagem , Apendicite/diagnóstico por imagem , Serviços Médicos de Emergência/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Tomografia Computadorizada por Raios X , Ultrassonografia de IntervençãoRESUMO
Grapefruit juice inhibits esterase enzyme. Therefore, a possible interaction with ester prodrugs should be taken into consideration. In this study, the influence of grapefruit juice on sacubitril (SAC) rat liver S9 activation by esterase enzyme was evaluated. An RP-HPLC method was developed and validated for estimation of SAC in rat liver S9 fraction using a C18 Cyano column as stationary phase and acetonitrile-sodium di-hydrogen phosphate buffer (0.02 m, pH 4 adjusted by o-phosphoric acid, 40:60, v/v), as mobile phase at a flow rate of 1 mL/min and UV detection at 254 nm. The method was successfully applied to an in vitro study in which SAC was incubated with rat liver S9 fraction prepared from rats that had previously ingested grapefruit juice for a week. The calculated SAC concentration after incubation was compared with that of SAC incubated with rat liver S9 fraction from the rat control group. The statistical significance between the results of test and control incubation sets was assessed. In conclusion, the current study demonstrated that grapefruit juice decreased SAC hydrolysis, hence delaying its activation to sacubitrilat (active form) in gut lumen. Based on this food-drug interaction, it may be required that grapefruit juice should be consumed with caution in patients receiving SAC.
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Aminobutiratos/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Citrus paradisi/química , Sucos de Frutas e Vegetais , Microssomos Hepáticos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tetrazóis/farmacologia , Aminobutiratos/farmacocinética , Animais , Compostos de Bifenilo , Combinação de Medicamentos , Limite de Detecção , Modelos Lineares , Extratos Vegetais/farmacocinética , Ratos , Reprodutibilidade dos Testes , Tetrazóis/farmacocinética , ValsartanaRESUMO
AIM: To assess serum 25-hydroxyvitamin D 25(OH)D level in obese pregnant Sudanese women in early pregnancy. METHODS: A match case-control study was conducted in Saad Abualila Hospital (Khartoum, Sudan). The cases were obese (body mass index [BMI] ≥ 30.0 kg/m2 ) women. Controls were women with normal BMI (18.5-24.9 kg/m2 ) matched for age, parity and gestational age. The 25(OH)D level was measured using ELISA. RESULTS: There was no significant difference between the two groups in their age, parity or gestational age. There was no significant difference in the median (interquartile) level of the serum (25(OH)D between obese pregnant women and normal weight pregnant women (3.05 [11.100-15.937] ng/ml vs 13.05 [10.950-17.362] ng/ml, P = 0.237). There was no significant correlation between BMI and 25(OH)D level (r = -0.133, P = 0.149). CONCLUSION: There was no significant difference in the 25(OH)D level between the obese pregnant women and normal weight pregnant women in this study.
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Obesidade/sangue , Complicações na Gravidez/sangue , Vitamina D/análogos & derivados , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Vitamina D/sangueRESUMO
BACKGROUND: United Arab Emirates, has reported the first case of COVID-19 in January 2020 and by October 2022, a total of 1 Million cases and 2348 deaths due to COVID-19 have been reported. The Abu Dhabi Public Health Center, has led a novel initiative to conduct a large scale genomic surveillance project. The aim of this surveillance project is to generate data to guide public health pandemic response decision making. METHODS: Samples mainly from the community, points of entry to the emirate and healthcare facilities were collected for surveillance using both targeted PCR and/or Genome sequence analysis. Sample criteria were defined and specific metadata were collected in parallel. Using the unique identifiers and through the available datasets, epidemiological and clinical data were integrated. RESULTS: A total of 385,191 sample undertake analysis (from January 2021 to October 2022) either genotyping and/or sequence analysis. The most frequently encountered lineages in the community and among severe cases were reported. CONCLUSIONS: Genomic surveillance is a major tool essential for guiding public health measures throughout the pandemic.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Saúde Pública , Emirados Árabes Unidos/epidemiologiaRESUMO
Aim: An eco-friendly ultra-performance liquid chromatography-tandem mass spectrometry method was developed to study the pharmacokinetics of rivaroxaban and ticagrelor in rat plasma, utilizing moxifloxacin as an internal standard. The food-drug interaction between grapefruit juice and these drugs was also investigated. Methods: Liquid-liquid extraction was used. A nonporous stationary phase Agilent® Poroshell 120EC C18 column was used with methanol: 0.1% aqueous formic acid (95:5 v/v) as a mobile phase. The detection was performed in multiple reaction monitoring mode using positive electrospray ionization. The method's validation was conducted in accordance with US FDA and European Medicines Agency guidelines. Results & conclusion: Grapefruit juice should be ingested with caution in patients treated with antithrombotic medications as it may increase their plasma concentration, inducing bleeding, and requires close clinical monitoring.
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Citrus paradisi , Espectrometria de Massas em Tandem , Ratos , Humanos , Animais , Espectrometria de Massas em Tandem/métodos , Rivaroxabana , Ticagrelor , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia LíquidaRESUMO
Three-levels Box-Behnken design was used in the experimental design approach for the optimization of chromatographic parameters to achieve the optimum resolution and sharp peak shape within a reasonable run time. A method that is sensitive, reliable, and selective was constructed and validated for the simultaneous measurement of a combination therapy that contains blood-thinning and cholesterol-lowering compounds. The four cited drugs namely, aspirin (ASP), clopidogrel (CLP), atorvastatin (ATV) and rosuvastatin (ROS) were estimated in bulk and in pharmaceutical dosage forms in line with International Council for Harmonization guidelines. The separation was done utilizing Kinetex 2.6 C18 column (100 mm, 4.6 mm, 5 m) and RP-HPLC with diode array detector. The separation of the cited drugs and the degradation product of ASP was achieved with mobile phase composed of acetonitrile: KH2PO4 buffer in a gradient mode with pH 3.2 at room temperature. The four drugs were linear over the concentration range (0.05-50 µg/mL). The technique is feasible to be used in quality control laboratories. To picture the green profile of the developed method, four greenness assessment tools were applied. National environmental methods index (NEMI), analytical eco-scale assessment (ESA), green analytical procedure index (GAPI) and analytical greenness metric (AGREE) are the most widely used metrics. They were employed to evaluate the greenness profile of the proposed method and to perform a detailed greenness comparison between the developed method and some of the reported methods for the determination of the investigated drugs. The developed method was found to be relatively green with 0.54 AGREE score.
RESUMO
RESEARCH AIMS: The aims of this study are to compare the knowledge and attitude scores between undergraduate and graduate nursing students and to identify the variables associated with higher breastfeeding knowledge and attitudes. BACKGROUND: Nurses' knowledge and attitudes towards breastfeeding greatly impact their roles in promoting and supporting breastfeeding. However, they may not have sufficient knowledge and/or positive attitudes to support and advocate for these families. Many studies focused on professional nurses or undergraduate students' knowledge, attitudes, and beliefs. Few studies included registered nurses enrolled in post licensure undergraduate and graduate nursing programs. DESIGN: A cross-sectional, prospective, and descriptive study. METHODS: A convenient sample of 95 nursing students (50 undergraduate and 45 graduate) was recruited from an ethnically diverse, urban university in Southern California. Students voluntarily completed an online survey adapted from Brodribb, et al. (2008). Bivariate analysis was conducted to identify relationships between study variables. RESULTS: Compared to undergraduates, graduate students scored higher on knowledge and attitudes towards breastfeeding (p < 0.001). Students' perception of their prior academic breastfeeding preparation was not related to their current knowledge and attitudes. Age, having children, exclusively breastfed own baby, and duration of personal breastfeeding were positively associated with attitudes and knowledge (p < 0.05 for all variables). Years of nursing experience (p = .01) was positively associated with attitudes only. CONCLUSIONS: Compared to academic preparation, age, having children, and personal breastfeeding experiences seem to be better indicators of breastfeeding knowledge and attitudes. Nursing programs should exert more effort in enhancing curricular evidence based breastfeeding education. More research is needed to support these efforts.