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2.
Bioorg Chem ; 147: 107409, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38714116

RESUMEN

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.


Asunto(s)
Antineoplásicos , Neoplasias , Sulfonamidas , Humanos , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Animales , Relación Estructura-Actividad
4.
Bioorg Chem ; 143: 107009, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38070474

RESUMEN

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.


Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas , Mycobacterium tuberculosis , Tiofenos , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/química , Simulación del Acoplamiento Molecular , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Relación Estructura-Actividad , Pruebas de Sensibilidad Microbiana
5.
BMC Chem ; 17(1): 164, 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38001500

RESUMEN

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.

6.
Bioanalysis ; 15(22): 1327-1341, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37902824

RESUMEN

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.


Asunto(s)
Citrus paradisi , Espectrometría de Masas en Tándem , Ratas , Humanos , Animales , Espectrometría de Masas en Tándem/métodos , Rivaroxabán , Ticagrelor , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida
7.
Nurse Educ Pract ; 72: 103758, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37660519

RESUMEN

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.


Asunto(s)
Bachillerato en Enfermería , Enfermeras y Enfermeros , Estudiantes de Enfermería , Femenino , Niño , Humanos , Lactancia Materna , Estudios Transversales , Competencia Clínica , Estudios Prospectivos , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios
8.
EClinicalMedicine ; 64: 102195, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37731938

RESUMEN

Background: COVID-19 vaccines that offer broad-spectrum protection are needed. We aimed to evaluate the safety and immunogenicity of multivalent vaccines, SCTV01E and SCTV01C, and compare them with an inactivated vaccine. Methods: In the phase 3 trial (ClinicalTrials.gov: NCT05323461), adult participants previously vaccinated with Sinopharm's inactivated SARS-CoV-2 vaccine (BBBIP-CorV) were assigned to receive one booster dose of BBBIP-CorV, 20 µg SCTV01C, or 30 µg SCTV01E. The primary endpoint was to evaluate the geometric mean titers (GMT) of neutralizing antibody (nAb) against the Delta and Omicron BA.1 variants on day 28 after injection. Additional endpoints included GMTs of nAb against Delta (B.1.617.2) and Omicron BA.1 variants on day 180, GMTs against BA.5 on day 28, as well as solicited adverse events (AEs) within seven days, unsolicited AEs within 28 days, and serious AEs, AEs of special interest within 180 days after vaccination. Findings: Between May 30, 2022 and October 28, 2022, a total of 1351 participants were randomized to BBBIP-CorV, SCTV01C, or SCTV01E in a 1:1:1 ratio, with immunogenicity assessments performed on the first 300 participants. For BBBIP-CorV, SCTV01C, and SCTV01E groups, the day 28 GMTs of neutralizing antibody against Omicron BA.1 were a 2.38-, 19.37-, and 28.06-fold increase from baseline; the GMTs against Omicron BA.5 were 2.07-, 15.89- and 21.11-fold increases; the GMTs against Delta variants were 1.97-, 12.76-, and 15.88-fold increases, respectively. The day 28 geometric mean ratio (GMR) of SCTV01C/BBIBP-CorV for Omicron BA.1 was 6.49 (95% CI: 4.75, 8.88), while the GMR of SCTV01E/BBIBP-CorV was 9.56 (95% CI: 6.85, 13.33). For the Delta variant, the day 28 GMR of SCTV01C/BBIBP-CorV was 6.26 (95% CI: 4.78, 8.19), and the day 28 GMR of SCTV01E/BBIBP-CorV was 7.26 (95% CI: 5.51, 9.56). On Day 180, the GMTs against Omicron BA.1 were 2.80-, 9.51-, and 15.56-fold increase from baseline, while those against Delta were 1.58-, 5.49-, and 6.63-fold for BBBIP-CorV, SCTV01C, and SCTV01E groups, respectively. Subgroup analyses showed that SCTV01C and SCTV01E induced uniformly high GMTs against both BA.1 and BA.5, demonstrating its superiority over BBIBP-CorV, regardless of baseline GMT levels. Safety and reactogenicity were similar among the three vaccines. Most AEs were Grade 1 or 2. There were 15 ≥Grade 3 AEs: 6 in the BBIBP-CorV group, 4 in the SCTV01C group and 5 in the SCTV01E group. No SAE was reported and one grade 1 AESI (Bell's palsy) was observed in SCTV01C group. Interpretation: A booster dose of the tetravalent vaccine SCTV01E consistently induced high neutralizing antibody responses against Omicron BA.1, BA.5, and Delta variants, demonstrating superiority over inactivated vaccine. There is evidence to suggest that SCTV01E may have GMT superiority over bivalent vaccine SCTV01C against Delta, BA.1 and BA.5 variants. Funding: This study was sponsored by Sinocelltech Ltd., and funded by the Beijing Science and Technology Planning Project [Z221100007922012] and the National Key Research and Development Program of China [2022YFC0870600].

9.
Nurs Educ Perspect ; 2023 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-37428646

RESUMEN

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.

10.
Nat Commun ; 14(1): 4043, 2023 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-37422518

RESUMEN

The safety and immunogenicity of a protein-based tetravalent vaccine SCTV01E that contains spike protein ectodomain (S-ECD) of Alpha, Beta, Delta and Omicron BA.1 are assessed and compared with bivalent protein vaccine SCTV01C (Alpha and Beta variants) and monovalent mRNA vaccine (NCT05323461). The primary endpoints are the geometric mean titers (GMT) of live virus neutralizing antibodies (nAb) to Delta (B.1.617.2) and Omicron BA.1 at day 28 post-injection. The secondary endpoints include the safety, day 180 GMTs against Delta and Omicron BA.1, day 28 GMTs to BA.5, and seroresponse rates of neutralizing antibodies and T cell responses at day 28 post-injection. 450 participants, comprising of 449 males and 1 female, with a median age (range) of 27 (18-62) years, are assigned to receive one booster dose of BNT162b2, 20 µg SCTV01C or 30 µg SCTV01E and completed 4-week follow-up. All SCTV01E related adverse events (AEs) are mild or moderate and no Grade ≥3 AE, serious AE or new safety concerns are identified. Day 28 GMT of live virus neutralizing antibodies and seroresponse against Omicron BA.1 and BA.5 with SCTV01E are significantly higher than those with SCTV01C and BNT162b2. These data indicate an overall neutralization superiority with tetravalent booster immunization in men.


Asunto(s)
Vacuna BNT162 , COVID-19 , Masculino , Humanos , Femenino , Lactante , COVID-19/prevención & control , SARS-CoV-2 , Anticuerpos Bloqueadores , Anticuerpos Neutralizantes , Anticuerpos Antivirales
11.
Infect Genet Evol ; 109: 105411, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36775046

RESUMEN

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.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Salud Pública , Emiratos Árabes Unidos/epidemiología
12.
Signal Transduct Target Ther ; 8(1): 20, 2023 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-36596779

RESUMEN

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.


Asunto(s)
COVID-19 , Vacunas , Adulto , Humanos , SARS-CoV-2 , COVID-19/prevención & control
13.
Artículo en Inglés | MEDLINE | ID: mdl-36674223

RESUMEN

(1) Background: Children spend a lot of time within schools. The school setting generally has many ergonomic hazards and reinforced behavior patterns which put children at greater risk of environmental hazards than adults during their critical developmental stages. (2) Objective: The aim of the current study was to investigate the prevalence of musculoskeletal disorders (MSDs) and detect spinal deformities amongst general and technical secondary school students. (3) Methods: A total of 418 students from the second grade of secondary school in Shaquira governorate, Egypt participated in this cross-sectional study. Each student in the study was screened via Nordic Musculoskeletal Questionnaire (NMQ) and had their upper limb posture measured via RULA (Rapid Upper Limb assessment), and the deviation in their thoracic curve was measured using a scoliometer. (4) Results: There was a prevalence of MSDs amongst students as there were 69.7% of general school students and 83.8% of the technical school students suffering from MSDs with a statistically significant difference between both technical and general school students in RULA score and musculoskeletal complaints, whereas there were non-statistical differences in the scoliometer scale in both general and technical education students. (5) Conclusions: Musculoskeletal problems are prevalent among Egyptian secondary school students, with higher prevalence between technical school students. Therefore, preventive measures and strategies are recommended to overcome the future complications of these musculoskeletal disorders.


Asunto(s)
Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Adulto , Niño , Humanos , Egipto/epidemiología , Prevalencia , Estudios Transversales , Ergonomía , Estudiantes , Enfermedades Musculoesqueléticas/etiología , Instituciones Académicas , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiología
14.
EBioMedicine ; 87: 104386, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36470077

RESUMEN

BACKGROUND: Booster vaccination is an efficient way to address the waning protection of vaccines and immune escape of SARS-CoV-2 variants. We aimed to assess the safety and immunogenicity of SCTV01C, a novel bivalent protein vaccine as a booster for people who previously received two doses of mRNA vaccine. METHODS: In this randomized, phase 1/2 trial, adults fully vaccinated with mRNA vaccines 3-24 month earlier were enrolled. Participants received SCTV01C at 20 µg, 40 µg or placebo. The primary endpoints were adverse reactions within 7 days and immunogenicity on Day 28 after vaccination. This trial was registered with ClinicalTrials.gov (NCT05043311). FINDINGS: Between January 27 and April 28, 2022, 234 adults were randomly assigned to receive SCTV01C or placebo. The most common solicited adverse events (AEs) were Grade 1 injection-site pain (10.7%) and pyrexia (6.3%). There were no reports of Grade 3 or above solicited AE, serious AEs or AEs of special interests. On Day 28 post the booster, the geometric mean concentrations (GMCs) of the specific binding IgG antibodies to spike protein for placebo, 20 µg and 40 µg SCTV01C were 1649, 4153 and 5354 BAU/mL, with fold of increase from baseline of 1.0, 2.8 and 3.4-fold, respectively. GMTs of neutralizing antibodies against live Delta variant were 1280, 3542, and 4112, with fold of increase of 1.1, 3.9 and 4.1-fold, respectively; GMTs of neutralizing antibodies against live Omicron variant were 218, 640, and 1083, with fold of increase of 1.1, 4.4 and 5.1-fold, respectively. Participants with low neutralizing antibody titers at baseline (below the lower limit of quantitation) had 64.0 and 49.4-fold of increase in GMTs for Delta and Omicron, respectively. INTERPRETATION: The heterologous booster of SCTV01C was safe, and induced uniformly high cross-neutralization antibody responses against Delta and Omicron variants. FUNDING: Beijing Science and Technology Plan Project (Z221100007922012) and the National Key Research and Development Program of China (2022YFC0870600) supported this study.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Adulto , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Método Doble Ciego , Vacunas de ARNm , SARS-CoV-2 , Vacunas Combinadas , Vacunas contra la COVID-19/efectos adversos
16.
Curr Med Res Opin ; 38(12): 2069-2075, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36274640

RESUMEN

BACKGROUND: Breakthrough infections post-COVID-19 vaccination occur with the emerging variants of the SARS-CoV virus which might be either due to the newer variants escaping immune response or the waning of antibodies over time. However, there is lack of long-term follow-up evidence on the waning of immune response following inactivated COVID-19 vaccine. METHODS: A retrospective, observational study was conducted on serum samples of individuals who had received two doses of BBIBP-CorV vaccine. Individual's antibody responses were evaluated based on IgG anti-S and neutralizing antibodies measurements. Antibody samples were categorized into four groups, defined by the time interval from the individual's receipt of the BBIBP-CorV vaccine: <30 days, 30-90 days, 91-180 days and >180 days. RESULTS: A total of 6668 serum samples from inactivated BBIBP-CorV vaccine recipients were analyzed for IgG anti-S and neutralizing antibodies. 571 (8.6%) samples were tested during the first 29 days interval post vaccination, 3642 (54.6%) were tested during 30-90 days interval, 2173 (32.6%) samples were tested during 91 to 180 days interval and 282(4.2%) were tested at >180 days interval post vaccination. We found that more than 50% of the individuals had antibody titers below the average cut-off range at the 91-180 days interval post vaccination. Older age (>60 years), male gender, chronic kidney disease, hypertension, immunodeficiencies and increased interval post vaccination emerged as independent risk factors associated with lower immune response. CONCLUSION: Inactivated BBIBP-CorV vaccine recipients, based on age, gender and associated comorbid conditions might need booster doses at an earlier interval than the currently followed six months interval.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Masculino , Humanos , Lactante , Estudios Retrospectivos , Vacunación , Anticuerpos Neutralizantes , Inmunoglobulina G
17.
Drug Dev Res ; 83(8): 1739-1757, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36074734

RESUMEN

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.


Asunto(s)
Analgésicos , Tiofenos , Animales , Humanos , Ratas , Analgésicos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios no Esteroideos/farmacología , Celecoxib/uso terapéutico , Cromatografía Liquida , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Edema/tratamiento farmacológico , Indometacina/farmacología , Espectrometría de Masas en Tándem , Tiofenos/farmacología
18.
J Hosp Palliat Nurs ; 2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36083224

RESUMEN

COVID-19 has taken 1 million lives as of March 22, 2022. The restrictions and enforced social distancing imposed because of the COVID-19 pandemic adversely affected the way people die, often alone in hospitals without their family members or loved ones by their side. Religious and cultural beliefs predominantly influence every aspect of people's lives, especially during the end of life (EOL). Islam is the fastest growing religion worldwide after Christianity and the third most practiced religion in the United States. The Islamic religion specifies how Muslim practice health and wellness, death, and EOL care. Islamic teachings provide a roadmap on EOL practices and death rituals that must be followed by the practicing individual. Scarce empirical studies exist on practices and rituals of Muslims near death and dying. Therefore, the aim of this case report is to provide a practical framework for health care practitioners to understand essential Islamic EOL practices and provide resources to guide clinical practice.

19.
Microchem J ; 181: 107769, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35855210

RESUMEN

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.

20.
Signal Transduct Target Ther ; 7(1): 172, 2022 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-35665745

RESUMEN

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01-63.85 folds on day 28 after vaccination, whereas only 4.20-16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Humanos , SARS-CoV-2
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