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1.
Cureus ; 16(2): e53797, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38465168

RESUMO

BACKGROUND: Mental illness is a disorder that can cause impairment and disability, affecting mood, thinking, and behavior; therefore, early intervention will reduce morbidity. This study aims to evaluate all the personal, family, societal, and medical barriers that prevent mental health patients from seeking consultation and treatment. METHODS: In Saudi Arabia, a cross-sectional study was conducted on 463 individuals aged 18 and above. Data were collected by face-to-face interviews using a validated questionnaire, which consisted of two parts. The first part included sociodemographic data, while the second part contained subsections of society/family, personal, and medical barriers. RESULTS: The results showed that 379 (81.9%) indicated that society and family barriers impacted them, whereas 325 (70.3%) believed that personal barriers hindered seeking help. However, 294 (63.5%) opted for medical barriers as a hindrance. Regarding the highest barriers, 120 of the total respondents (25.9%) saw psychiatric illness as a source of shame and stigma, 166 respondents (35.9%) said that the psychiatric patient is seen as crazy, 159 of them (34.3%) believed it is tough for anyone to talk about their feelings and emotions and 183 respondent (39.5%) feared that psychiatric illness would decrease the chance of marriage to the appropriate person. Our findings also indicated a low trust in hospital treatment, hence a loss of confidence in using medications. CONCLUSION: The findings of this study indicate that societal stigma is the most common barrier preventing people from seeking mental health consultation. Many barriers differ significantly between males and females.

2.
Exp Clin Transplant ; 22(Suppl 1): 290-298, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38385415

RESUMO

OBJECTIVES: Renal complications of COVID-19 are not yet well studied. We aimed to evaluate acute kidney injury prevalence among hospitalized patients with COVID-19 infection and explore its effect on patient outcomes. MATERIALS AND METHODS: We retrospectively evaluated 586 hospitalized patients with COVID-19. Of these patients, 267 (45.5%) developed acute kidney injury, as classified according to the Kidney Disease Improving Global Outcomes guidelines. We compared this group with 319 patients (54.5%) without acute kidney injury. RESULTS: Most patients in both study groups were men; mean age was 60.8 ± 14 versus 51.7 ± 16 years. Comorbid conditions that were substantially predominant among patients with acute kidney injury were diabetes mellitus (64% vs 42.9%), hypertension (72.6% vs 43.5%), and ischemic heart disease (25% vs 14.7%). Fever, cough, shortness of breath, and dehydration were the main presentations among patients with acute kidney injury, and patients in this group had greater prevalence of radiological findings concordant with COVID-19 (86.8% vs 59.8%). Sepsis, volume depletion, shock, arrhythmias, and acute respiratory distress syndrome were higher in patients with acute kidney injury. Anticoagulation (85% vs 59.2%), vasopressors, plasma infusions, antimicrobials, and steroids were more frequently used in patients with acute kidney injury. More patients with acute kidney injury had acute respiratory failure requiring mechanical ventilation (62.3% vs 32.9%), with higher overall mortality rate (63.2% vs 31.1%). CONCLUSIONS: We found more frequent prevalence of acute kidney injury associated with severe COVID-19 than shown in reports from Chinese, European, and North American cohorts. Patients with COVID-19 who developed acute kidney injury had risk factors such as hypertension and diabetes, greater need for mechanical ventilation, were males, and were older age. Mortality was high in this population, especially among older patients and those who developed Kidney Disease Improving Global Outcomes stage 3 disease.


Assuntos
Injúria Renal Aguda , COVID-19 , Hipertensão , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , COVID-19/diagnóstico , COVID-19/terapia , SARS-CoV-2 , Estudos Retrospectivos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Fatores de Risco , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia
3.
Int J Biol Macromol ; 253(Pt 7): 127350, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37838117

RESUMO

This study aims at the development of electrospun polylactic acid nanofibers (PLLA NFs) incorporating smart daclatasvir-loaded chitosan gelatin nanoparticles to be used as medical textiles. First, smart nanoparticles were prepared through ionic gelation and optimized using Design Expert® software where daclatasvir (DAC), chitosan (CS), and gelatin (GL) amounts were selected to be the independent variables. DAC was used owing to its reported Anti-SARS-CoV-2 activity, CS was chosen due to its antimicrobial activity and GL was used owing to its sensitivity to be hydrolyzed upon exposure to Papain-like protease enzyme (PLpro). The optimum DAC-CS/TAN NPs possessed 109 nm size and 94.44 % entrapment efficiency in addition to sustained drug release for 14 days. Furthermore, upon exposure to PLpro, smart DAC-CS/GL NPs released the whole DAC amount within 3 h. Then, DAC-CS/GL NPs were incorporated within PLLA NFs through electrospinning. Swellability was found to increase gradually reflecting the controlled release of DAC from nanofibers within 3 weeks. Cell viability assessments using human fibroblasts showed that the developed nanofibers possess high biocompatibility. An in-vivo animal model for skin irritation was carried out for two weeks where visual inspection and histopathological investigations showed that neither edema nor erythema were observed.


Assuntos
Anti-Infecciosos , COVID-19 , Quitosana , Nanofibras , Nanopartículas , Animais , Humanos , Gelatina
4.
Pharmaceutics ; 15(8)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37631287

RESUMO

A significant number of deaths are reported annually worldwide due to microbial and viral infections. The development of protective medical textiles for patients and healthcare professionals has attracted many researchers' attention. Therefore, this study aims to develop smart drug-eluting nanofibrous matrices to be used as a basic material for medical textile fabrication. First, chitosan/gelatin nanofibers were selected as the basic material owing to the wide antimicrobial activity of chitosan and the capability of gelatin to be hydrolyzed in the abundance of the papain-like protease (PLpro) enzyme secreted by SARS-CoV-2. Daclatasvir (DAC), an NS5A inhibitor, was selected as the model drug based on in silico studies where it showed high anti-SARS-CoV-2 potential compared to FDA-approved references. Due to their reported antimicrobial and antiviral activities, ZnO NPs were successfully prepared and incorporated with daclatasvir in chitosan/gelatin nanofibrous matrices through electrospinning. Afterward, an in vitro release study in a simulated buffer revealed the controlled release of DAC over 21 days from the nanofibers compared to only 6 h for free DAC. On the other hand, the abundance of PLpro induced the complete release of DAC from the nanofibers in only 4-8 h. Finally, the nanofibers demonstrated a wide antimicrobial activity against S. aureus, E. coli, and C. albicans.

5.
Methods Appl Fluoresc ; 11(4)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37586384

RESUMO

Green, one-pot, quick, and easily synthesized nitrogen and sulfur co-doped carbon quantum dots (N,S-CDs) were obtained from cheap and readily available chemicals (sucrose, urea, and thiourea) using a microwave-assisted approach in about 4 min and utilized as a turn-off fluorescent sensor for estimation of natamycin (NAT). First, the effect of N and S doping on the microwave-synthesized CDs' quantum yield was carefully studied. CDs derived from sucrose alone failed to produce a high quantum yield; then, to increase the quantum yield, doping with heteroatoms was carried out using either urea or thiourea. A slight increase in quantum yield was observed upon using thiourea with sucrose, while an obvious enhancement of quantum yield was obtained when urea was used instead of thiourea. Surprisingly, using a combination of urea and thiourea together results in N,S-CDs with the highest quantum yield (53.5%), uniform and small particle size distribution, and extended stability. The fluorescent signal of N,S-CDs was quenched upon addition of NAT due to inner filter effect and static quenching in a manner that allowed for quantitative determination of NAT over a range of 0.5-10.0µg ml-1(LOD = 0.10µg ml-1). The N,S-CDs were applicable for determination of NAT in aqueous humor, eye drops, different environmental water samples, and bread with excellent performance. The selectivity study indicated excellent selectivity of the prepared N,S-CDs toward NAT with little interference from possibly interfering substances. In-silico toxicological evaluation of NAT was conducted to estimate its long-term toxicity and drug-drug interactions. Finally, the preparation of N,S-CDs, and analytical procedure compliance with the green chemistry principles were confirmed by two greenness assessment tools.


Assuntos
Natamicina , Pontos Quânticos , Pontos Quânticos/química , Carbono/química , Micro-Ondas , Ureia , Tioureia
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 292: 122399, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-36724684

RESUMO

The purpose of the present work was to establish a fast and convenient strategy for lomefloxacin analysis using a fluorimetric approach. The methodology was based on the complex formation of the drug with aluminum ion to give a product having high fluorescence. Adding sodium dodecyl sulfate led to further boosting the intensity of fluorescence which was recorded at 429 nm after excitation at 332 nm. The relationship of emission intensity with lomefloxacin concentration was linear at 10-130 ng mL-1 with a correlation coefficient of 0.9996. The quantitation limit was 11.4 ng mL-1 and detection limit was 3.8 ng mL-1. The reaction conditions were carefully studied which included the pH, buffer type, its concentration, the type and concentration of surfactant and the diluting solvent. The method was utilized to quantify the aforementioned drug in tablet formulations and in real human plasma with high accuracy and reliability.


Assuntos
Fluoroquinolonas , Metais , Humanos , Espectrometria de Fluorescência/métodos , Reprodutibilidade dos Testes , Fluoroquinolonas/análise , Solventes
7.
Luminescence ; 38(1): 39-46, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36482153

RESUMO

Methylglyoxal (MGO) is a genotoxic α-dicarbonyl compound. Recently, it was found to be formed in glycerol preparations during storage through auto-oxidation. A simple fluorimetric determination of the carcinogenic degradation product of glycerol, MGO, was developed and validated. The proposed method is based on the derivatization of MGO with 4-carbomethoxybenzaldehyde (CMBA) and ammonium acetate to yield a fluorescent imidazole derivative that can be measured at 415 nm after excitation at 322 nm. The optimized conditions were determined to be 0.2 M CMBA, 1.0 M ammonium acetate and a reaction time of 40 min at 90°C using ethanol as diluting solvent. The linear range was 10.0-200.0 ng/ml. Detection and quantification limits were 2.22 and 6.72 ng/ml, respectively. The proposed method was validated according to International Council for Harmonisation (ICH) guidelines and compared with the reported method and no significant difference was found. It was successfully applied for the determination of MGO in six different glycerol-containing pharmaceutical preparations and dietary supplements.


Assuntos
Glicerol , Aldeído Pirúvico , Espectrometria de Fluorescência/métodos , Óxido de Magnésio , Suplementos Nutricionais , Preparações Farmacêuticas
8.
Cureus ; 15(12): e49868, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38169912

RESUMO

Sepsis is a life-threatening emergency that arises owing to a dysregulated host response to infection, leading to existence organ dysfunction. Vitamin C administration has led to a lower mortality rate in sepsis. N-acetylcysteine (NAC) treatment during sepsis improves hepatic function and enhances tissue oxygenation. The objective of this case report is to investigate the synergistic effect of the combination of vitamin C, thiamine, and NAC in delaying sepsis cascade and prolongation of survival time. In this case report, an oral dose of vitamin C 500 mg three times daily in combination with IV thiamine 100 mg three times daily, IV NAC, and hydrocortisone stress dose resulted in 12 days of survival of an immunocompromised patient with ventilator-associated pneumonia on single anti-pseudomonas beta-lactam antibiotic. The patient was a 60-year-old Malay female with previous bone marrow transplantation surgery and a medical history of ischemic stroke on phenytoin and valproate therapy. The patient was transferred to a medical ward in Penang General Hospital, Malaysia, due to community-acquired pneumonia. She was on ceftriaxone for five days, then sedated and ventilated in the ICU, with a shift to cefepime for three days, which was then changed to meropenem for nine days until the last day of life. Total anti-pseudomonas coverage was 12 days. The patient had multiple comorbidities from phenytoin-induced hepatic encephalopathy, acute kidney injury, and three sessions of hemodialysis. IV vitamin C was not available, so an oral dose was administered with potential efficacy in delaying the sepsis inflammatory cascade, leading to the use of a single (not double) anti-pseudomonas antibiotic for 12 days. Prolonged survival duration may be expected in the case of normal bone marrow patients with ventilator-associated pneumonia sepsis. In conclusion, Vitamin C, thiamine, and NAC combination resulted in delayed sepsis progression for 12 days and the survival of the immunocompromised patient on a single anti-pseudomonas beta-lactam antibiotic.

9.
Sci Rep ; 12(1): 15319, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097190

RESUMO

A green spectrofluorimetric method was introduced for the determination of selected genotoxic impurities; 2-aminopyridine and 3-aminopyridine in different pharmaceutical raw materials and dosage forms. The method relied on the native fluorescence of these impurities in acidic medium. The experimental conditions were carefully studied and optimized, and the method was validated according to International Council on Harmonisation (ICH) guidelines. The linear range for both analytes was 2.50-100 ng/mL with good determination coefficients of 0.9995 and 0.9992 and detection limits of 0.62 ng/mL and 0.74 ng/mL for 2-aminopyridine and 3-aminopyridine, respectively. The method was successfully applied for determination of 2-aminopyridine and 3-aminopyridine in four active pharmaceutical ingredients and nine dosage forms with satisfactory percentage recoveries and without interference from co-formulated excipients. Analytical performance of the proposed method was comparable to that of the reported methods; hence, the proposed method can be used as a simple and low-cost alternative in quality control laboratories.


Assuntos
Dano ao DNA , Calibragem , Preparações Farmacêuticas , Espectrometria de Fluorescência/métodos
10.
Life (Basel) ; 12(6)2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35743948

RESUMO

This study was conducted to investigate the effect of the Ficus sycomorus extract on Eimeria intestinalis in experimentally infected rabbits. For this purpose, forty male 30-day-old rabbits (Blanc de Bouscat) were divided into four groups (n = 10 in each group). Rabbits kept in the first group served as negative control (non-treated-non-infected). Rabbits kept in the second, third, and fourth groups were challenged at 10 weeks old with 3 × 104E. intestinalis sporulated oocysts. The third and fourth groups were treated orally with diclazuril 10% (0.05 mg/kg body weight) and F. sycomorus (100 mg/Kg) for three consecutive days, respectively. The efficacy was assessed based on the growth performance parameters, clinical symptoms, oocyst shedding, histopathological findings, and hematological parameters for 16 days post challenge. The study revealed that rabbits treated with F. sycomorus methanolic extract and diclazuril showed mild clinical symptoms with a significant decrease in oocyst shedding compared with the positive control. Moreover, the diclazuril-treated group showed the highest leukocytic count and the lowest monocytes percentage compared with other groups. Furthermore, the lowest lymphocytes percentage was recorded in the control positive group. Histopathologically, moderate coccidia infestation in the intestinal mucosa and moderate hydropic degeneration of hepatocytes were observed in the diclazuril treated group compared with the negative control. However, mild coccidia infestation in the intestinal mucosa and slight coagulative necrosis of hepatocytes was found in the F. sycomorus treated group. In conclusion, F. sycomorus methanolic extract had promising effects on the live performance, oocyst count, and blood variables, while it possesses adverse consequences on the hepatic tissues. Further studies are required to optimize the dose and extraction method to mitigate its side effects.

11.
BMC Chem ; 16(1): 33, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568922

RESUMO

A vortex-assisted dispersive liquid-liquid microextraction (DLLME) method, mated to chemometrics and combined with HPLC/UV detection was optimized and validated for enrichment and determination of repaglinide in environmental samples using nateglinide as an internal standard (IS). A phosphate buffer (10 mM, pH 2.5): acetonitrile (45:55, v/v) was used as a mobile phase with a flow rate of 1 mL/min in an isocratic elution mode. Chemometrics-assisted optimization was performed using a quadratic integrated D-optimal design. The developed model assessed the statistical significance of the independent variables and their interactions to attain the optimum conditions revealing that extractant type, extractant volume and pH are the most influential factors. Optimization of the extraction procedures was performed with the aid of Design Expert 8® software, which suggested 58 different experiments. The optimal conditions were 30 µL of 1-octanol as extractant, 100 µL of acetonitrile as a disperser at pH 8. Under the optimized conditions, the method showed linearity over the range of 1-100 ng/mL with a limit of detection of 0.4 ng/mL. The accuracy, the intra- and inter-day precision were assessed, the %recoveries were found to be between 98.48 and 100.81% with %RSD lower than 1.3. Using chemometrics in method optimization helped achieve the maximum possible enrichment with the least effort, time, and reagents while considering all possible interactions between variables.

12.
Clin Transplant ; 35(6): e14297, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33768630

RESUMO

INTRODUCTION: COVID-19 is an ongoing pandemic with high morbidity and mortality and with a reported high risk of severe disease in kidney transplant recipients (KTR). AIM: We aimed to report the largest number of COVID-19-positive cases in KTR in a single center and to discuss their demographics, management, and evolution. METHODS: We enrolled all the two thousand KTR followed up in our center in Kuwait and collected the data of all COVID-19-positive KTR (104) from the start of the outbreak till the end of July 2020 and have reported the clinical features, management details, and both patient and graft outcomes. RESULTS: Out of the one hundred and four cases reported, most of them were males aged 49.3 ± 14.7 years. Eighty-two of them needed hospitalization, of which thirty-one were managed in the intensive care unit (ICU). Main comorbidities among these patients were hypertension in 64.4%, diabetes in 51%, and ischemic heart disease in 20.2%. Management strategies included anticoagulation in 56.7%, withdrawal of antimetabolites in 54.8%, calcineurin inhibitor (CNI) withdrawal in 33.7%, the addition of antibiotics in 57.7%, Tocilizumab in 8.7%, and antivirals in 16.3%. During a follow-up of 30 days, the reported number of acute kidney injury (AKI) was 28.7%, respiratory failure requiring oxygen therapy 46.2%, and overall mortality rate was 10.6% with hospital mortality of 13.4% including an ICU mortality rate of 35.5%. CONCLUSION: Better outcome of COVID-19-positive KTR in our cohort during this unremitting stage could be due to the younger age of patients and early optimized management of anticoagulation, modification of immunosuppression, and prompt treatment of secondary bacterial infections. Mild cases can successfully be managed at home without any change in immunosuppression.


Assuntos
COVID-19 , Transplante de Rim , Anticoagulantes/uso terapêutico , Feminino , Humanos , Terapia de Imunossupressão , Transplante de Rim/efeitos adversos , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Transplantados
13.
J Chromatogr Sci ; 59(3): 297-304, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33275653

RESUMO

A validated method for preconcentration and determination of nateglinide in plasma was developed using vortex-assisted dispersive liquid-liquid microextraction. Different variables that affect extraction efficiency were studied and optimized, including type and volume of extractant, type and volume of disperser, pH of diluent, salt addition effect, centrifugation and vortex time. Nateglinide was extracted using 30 µL of 1-octanol as an extractant and 200 µL of methanol as a disperser. The enrichment factor reached 330 under the optimum conditions. High-performance liquid chromatography/ultraviolet was used for detection using phosphate buffer (pH 2.5, 10 mM): acetonitrile (45:55, v/v) as a mobile phase at a flow rate of 1 mL/min. The method was linear over the range of 50-20,000 ng/mL with a limit of detection of 15 ng/mL (signal-to-noise ratio = 3). Intra- and inter-day precision had %relative standard deviation <6% (n = 3) and the %recoveries were found to be between 102.5 and 105.9%. The proposed method is simple, sensitive, eco-friendly, cost-effective and powerful for microextraction of nateglinide from human plasma samples.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Microextração em Fase Líquida/métodos , Nateglinida/sangue , Humanos , Limite de Detecção , Modelos Lineares , Nateglinida/isolamento & purificação , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta
14.
Braz. J. Pharm. Sci. (Online) ; 57: e18954, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1345456

RESUMO

The ethanolic extract of resinous sediment (EERS) of Etlingera elatior young inflorescence was examined for its anticancer effect and potential antioxidant activity. The anticancer effect of the EERS was evaluated on four human cancer cell lines, HCT 116, HT-29, Hela, and MCF-7, using the MTT assay. GC-MS analysis showed that the main components found in the EERS were nonyl cyclopropane (4.44%), 1-tetradecane (3.66%), cyclotetradecane (2.41%), cyclododecane (1.92%), and 1-decene (1.72%). The antioxidant activity was determined through different methods. High amounts of TPC and TFC in the EERS were found. Moderate antioxidant capacity of the EERS was detected by DPPH and ABTS assays, with EC50 values of 44.19 and 56.61 µg/mL and a high FRAP value of 281.79 nmol Fe+2 equivalent/mg extract. In the MTT assay, the EERS showed potent anticancer activity, with IC50 values of 19.82, 37.001, 50.49, and 53.29 µg/mL against HT-29, HCT 116, Hela, and MCF-7 tumour cell lines, respectively. Moreover, the results were comparable to or less potent than the standard reference drug, 5-fluorouracil. The results showed that the EERS of Etlingera elatior inflorescence contained a high amount of polyphenols and flavonoids, which may to the selective antiproliferative effects towards colon cancer in vitro


Assuntos
Zingiberaceae/classificação , Inflorescência/anatomia & histologia , Fluoruracila/farmacologia , Neoplasias , Antioxidantes/análise , Técnicas In Vitro/métodos , Preparações Farmacêuticas , Anticarcinógenos/efeitos adversos , Neoplasias do Colo/patologia
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 240: 118624, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32604051

RESUMO

Herein, a selective and rapid spectrofluorimetric method coupled with experimental design approach for reliable and efficient determination of two α-blockers, namely: terazosin hydrochloride (TER) and doxazosin mesylate (DOX) in their marketed tablets was developed. The presented method adopts formation of a semi-quinoid form of the studied drugs in borate buffer. The effects of parameters influencing fluorescence intensity including pH, the volume of buffer and diluting solvent were optimized using an experimental design methodology. The optimum conditions were found to be pH: 9.8, the volume of buffer: 2.0 mL and diluting solvent: water. Under the optimum experimental conditions, a large enhancement of the studied drugs fluorescence was obtained, measured at 387 after excitation at 246 nm for either TER or DOX with limits of detection 0.05 and 0.14 ng mL-1 and limits of quantification 0.14 and 0.43 ng mL-1 in the concentration ranges of 0.2-30.0 ng mL-1 and 0.5-30.0 ng mL-1 for TER and DOX, respectively. The presented method was validated according to the ICH guidelines. Furthermore, it extended to perform the content uniformity testing and analysis of the studied drugs in spiked human plasma with % recovery (96.00 ± 0.45-101.42 ± 1.20%, n = 3).


Assuntos
Doxazossina , Projetos de Pesquisa , Antagonistas Adrenérgicos alfa , Fluorescência , Humanos , Espectrometria de Fluorescência , Comprimidos
16.
Diabetes Metab Syndr ; 14(4): 341-346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32305775

RESUMO

BACKGROUND: Peripheral neuropathy (PN) is a complaint with often unidentified reasons. Some medicines, including statins therapy, are anticipated to be amongst the reasons for PN. AIMS: This study intended to assess the association of peripheral neuropathy with statins therapy amongst Type 2 diabetic patients. METHODS: At Penang General Hospital, 757 cases were categorized into two groups (564 with statins therapy and 193 without statins therapy). The diagnosis of PN was investigated retrospectively for a period of 10 years (2006-2016). Confounding risk factors as age, diabetes period, hypertension, glycemic control, other co-morbidity, and prescriptions were matched. RESULTS: About 129 (22.9%) cases from 564 statins users had PN. Only 30 (15.5%) subjects had PN from 193 statins non-users. Chi-square test showed a significant variance among statins treatment cohort and statin-free cohort in the occurrence of PN (P-value: 0.001). Spearman's investigation presented a positive correlation (r: 0.078, p-value: 0.031) among statins use and PN prevalence. Binary logistic regression was statistically significant for statins therapy as a predictor of peripheral neuropathy incidence (r2: 0.006, p-value: 0.027) amid diabetic patients. The relative risk of peripheral neuropathy connected with statins therapy is (RR: 1.47, 95% CI: 1.02-2.11). The excess relative risk is 47.1%. While the absolute risk (AR) is 7.3% and the number needed to harm (NNH) is 14. CONCLUSIONS: The study indicated a positive association between peripheral neuropathy and statins utilization. Peripheral neuropathy was higher amongst statins users than the statins-free group.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Neuropatias Diabéticas/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Biomarcadores/análise , Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/induzido quimicamente , Neuropatias Diabéticas/patologia , Feminino , Seguimentos , Humanos , Incidência , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
17.
Stem Cell Res Ther ; 10(1): 290, 2019 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547869

RESUMO

BACKGROUND: Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite remarkable short-term recovery, long-term lung survival continues to face several major challenges, including chronic rejection and severe toxic side effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The novel Cymerus™ manufacturing facilitates production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. METHODS: Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c → C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium, and collagen deposition during rejection. RESULTS: We demonstrated that iPSC-derived MSC treatment leads to significant increases in hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, and IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post transplantation. CONCLUSIONS: Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune tolerance and rescue allograft from sustained hypoxic/ischemic phase, and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.


Assuntos
Rejeição de Enxerto/terapia , Sobrevivência de Enxerto , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Órgãos/métodos , Traqueia/transplante , Tolerância ao Transplante , Animais , Células Cultivadas , Rejeição de Enxerto/imunologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/imunologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante de Órgãos/efeitos adversos , Linfócitos T Reguladores/imunologia
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 217: 182-189, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30933783

RESUMO

A simple selective luminescent dependent approach was established for quantitation of two selective ß2 agonists namely; Fenoterol hydrobromide (FEN) and Salmeterol xinafoate (SAL). This approach utilizes the capability of the cited drugs to undergo a complexation reaction with Europium ion (Eu3+) in the presence of 1,10-phenanthroline as a co-ligand. The resultant complex leads to a hypersensitive transition and enhancement of the Eu3+ emission peak at 615nm (279nm excitation). Under the optimized conditions, the rectilinear concentration plots of both drugs were (70-1500ngmL-1) and (100-2000ngmL-1) with limit of quantitation 51.3 and 84.4ngmL-1 for FEN and SAL, respectively. The luminescence properties of the complex and its optimum formation conditions were carefully investigated according to the regulations of ICH and the method was successfully applied in plasma. The good accuracy and selectivity of the suggested method allowed extending the proposed protocol into stability study of the cited drugs.


Assuntos
Európio/química , Fenoterol/sangue , Fenoterol/química , Xinafoato de Salmeterol/sangue , Xinafoato de Salmeterol/química , Estabilidade de Medicamentos , Humanos
19.
Luminescence ; 33(7): 1226-1234, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30094938

RESUMO

Alpha1-adrenergic-blocking drugs, namely; alfuzosin hydrochloride (ALF), doxazosin mesylate (DOX) and terazosin hydrochloride (TER) are effective as antihypertensive agents as well as in management of benign prostatic hypertrophy. In this study, a simple, very fast, highly sensitive and cheap technique was optimized for assay of these drugs in pure states and pharmaceutical tablets. The proposed method is dependent on enhancement of the native fluorescence of investigated drugs using the polyoxyethylene 50 stearate (POE50S) micellar system. The method showed excitation at 325, 340 and 250 nm for ALF, DOX and TER, respectively and an emission maxima at 382 nm. The fluorescence intensity-concentration charts of studied drugs were attained utilizing concentration ranges (2.0-60.0 ng mL-1 ) for DOX and (4.0-100.0 ng mL-1 ) for ALF and TER with quantitation limits 2.9, 1.6 and 2.5 ng mL-1 for ALF, DOX and TER, respectively. The suggested technique was approved according to International Council for Harmonisation (ICH) standards and the United States Food and Drug Administration (US FDA) bioanalytical method validation and has been effectively applied for assay of these medications in their dosage forms as well as for content uniformity test. The developed procedure was also efficiently applied for determination of these drugs in real human plasma with high accuracy.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/sangue , Anti-Hipertensivos/sangue , Espectrometria de Fluorescência/métodos , Doxazossina/sangue , Fluorescência , Humanos , Limite de Detecção , Micelas , Preparações Farmacêuticas/sangue , Plasma/química , Prazosina/análogos & derivados , Prazosina/sangue , Quinazolinas/sangue , Comprimidos/química
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 204: 702-707, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-29982162

RESUMO

A new, specific, precise and very sensitive spectrofluorimetric methodology has been established and approved for determination of Fenoterol hydrobromide (FEN) in its pharmaceutical forms and spiked plasma. The strategy utilized the phenolic nature of FEN and its capacity to undergo Von Pechman synthesis of coumarin. In this study, Fenoterol hydrobromide reacts with ethyl acetoacetate in presence of concentrated sulfuric acid to form an extremely fluorescent coumarin derivative measured at 480 nm (λex: 420 nm). Different reaction variables affecting development and stability of the formed coumarin derivative were precisely examined and enhanced to guarantee greatest sensitivity of the strategy. The recommended procedure was found to obey Beer's law in concentration range of (300-2000) pg mL-1 with quantitation limit 130 pg mL-1, revealing high sensitivity of the suggested method. The proposed procedure was completely examined and approved through the ICH guidelines and was efficiently applied for the determination of the cited drug in spiked plasma and its dosage forms.


Assuntos
Cumarínicos/química , Fenoterol/análise , Fenoterol/química , Corantes Fluorescentes/química , Espectrometria de Fluorescência/métodos , Fenoterol/sangue , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Ácidos Sulfúricos
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