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1.
J Microencapsul ; 37(6): 413-430, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32421463

RESUMO

Aim: This work aimed to develop topical nanoemulsion gels of cetirizine, a second-generation antihistamine, to avoid its oral intake drawbacks and enhance skin permeation.Methods: Cetirizine nanoemulsions were formulated and characterised for their particle size, polydispersity index, zeta potential, drug release and drug permeation through rat skin. The optimised formulation, obtained using 23 full factorial design, was incorporated in carbopol and chitosan gels and evaluated clinically for urticaria treatment.Results: The optimised formulation had particle size of 32.015 ± 1.87 nm, polydispersity index of 0.29 ± 0.04, zeta potential of -19.31 ± 0.43 mV, cetirizine percent released of 98.50 ± 1.23% and permeability coefficient of 7.65 cm.h-1. Cetirizine nanoemulsion gels were more effective than their control gels in urticaria treatment with significant decrease in the degree of wheals and itching and higher recovery percent.Conclusion: Cetirizine nanoemulsion topical gels are expected to be a rational and effective tool for avoiding cetirizine oral side effects and targeting the affected skin.


Assuntos
Cetirizina/administração & dosagem , Sistemas de Liberação de Medicamentos , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Adolescente , Adulto , Animais , Cetirizina/química , Cetirizina/farmacocinética , Composição de Medicamentos , Liberação Controlada de Fármacos , Emulsões , Géis , Humanos , Masculino , Nanoestruturas , Tamanho da Partícula , Prurido/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Pele/metabolismo , Adulto Jovem
2.
J Surg Res ; 243: 539-552, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31377495

RESUMO

BACKGROUND: Frailty predicts poor outcome after vascular surgery. We determined the predictive utility of the modified frailty index (mFI) after first-time revascularization and identified biomarkers of frailty predictive of outcome in veterans with peripheral arterial disease. METHODS: A retrospective study was performed of first-time revascularizations (open surgery [OS] and endovascular surgery [ES]) in male veterans (2003-2016). Preoperative mFI scores were calculated, and serum and nonserum biomarkers of frailty were recorded. The primary endpoint was 2-y incidence of reintervention, amputation, and mortality. Secondary endpoints included 30-day morbidity and readmissions. RESULTS: Four hundred and thirty one patients (OS, n = 188; ES, n = 243), mean age of 66 ± 9 y, and 16 mo of median follow-up were studied. Mean mFI was 0.39 ± 0.16 for OS and 0.38 ± 0.15 for ES (P = 0.43). 30-day complications (adjusted odds ratio, 4.89; 95% confidence interval [CI]: 1.67-14.33) and readmissions (adjusted hazard ratio [aHR] 3.32; 95% CI: 1.16-9.55) were increased in the OS versus ES group when stratified by mFI. Survival analysis showed a correlation between risk of amputation, death, and composite outcome with increasing mFI (P < 0.005) in both groups. Frailty independently predicted major amputation (aHR 2.16; 1.06-4.39), mortality (aHR 2.62; 95% CI: 1.17-5.88), and composite outcome (aHR 1.97; 95% CI: 1.06-3.68) when the groups are combined. Except for absolute neutrophil count, all preoperative lab values correlated with mFI (P < 0.5). Higher albumin was independently associated with lower risk of amputation (aHR: 0.58 [0.36-0.94]) and mortality (aHR: 0.45 [0.25-0.83]); higher hemoglobin predicted limb salvage (aHR 0.7 [0.62-0.84]). CONCLUSIONS: Frailty predicts short- and long-term outcomes after first-time revascularization in veterans. Hypoalbuminemia and anemia are associated with higher mFI and independently predict poor outcome, suggesting albumin and hemoglobin are viable biomarkers of frailty in veterans.


Assuntos
Procedimentos Endovasculares/mortalidade , Fragilidade/complicações , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Biomarcadores/sangue , Fragilidade/sangue , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Doença Arterial Periférica/complicações , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Veteranos/estatística & dados numéricos
3.
AAPS PharmSciTech ; 19(5): 2155-2173, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29714001

RESUMO

Felodipine has a very low bioavailability due to first-pass metabolism. The aim of this study was to enhance its bioavailability by transdermal application. Felodipine-loaded transferosomes were prepared by thin-film hydration using different formulation variables. An optimized formula was designed using statistical experimental design. The independent variables were the used edge activator, its molar ratio to phosphatidylcholine, and presence or absence of cholesterol. The responses were entrapment efficiency of transferosomes, their size, polydispersity index, zeta potential, and percent drug released after 8 h. The optimized formula was subjected to differential scanning calorimetry studies and its stability on storage at 4°C for 6 months was estimated. This formula was improved by incorporation of different permeation enhancers where ex vivo drug flux through mice skin was estimated and the best improved formula was formulated in a gel and lyophilized. The prepared gel was subjected to in vivo study using Plendil® tablets as a reference. According to the calculated desirability, the optimized transferosome formula was that containing sodium deoxycholate as edge activator at 5:1 M ratio to phosphatidylcholine and no cholesterol. The thermograms of this formula indicated the incorporation of felodipine inside the prepared vesicles. None of the tested parameters differed significantly on storage. The lyophilized gel of labrasol-containing formula was chosen for in vivo study. The relative bioavailability of felodipine from the designed gel was 1.7. In conclusion, topically applied lyophilized gel containing felodipine-loaded transferosomes is a promising transdermal delivery system to enhance its bioavailability.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Felodipino/administração & dosagem , Géis/administração & dosagem , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Animais , Animais Recém-Nascidos , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Felodipino/química , Felodipino/metabolismo , Liofilização , Géis/química , Géis/metabolismo , Lecitinas/administração & dosagem , Lecitinas/química , Lecitinas/metabolismo , Lipossomos , Camundongos , Absorção Cutânea/fisiologia , Comprimidos , Adesivo Transdérmico
4.
AAPS PharmSciTech ; 19(4): 1529-1543, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29470829

RESUMO

Serious adverse effects and low selectivity to cancer cells are the main obstacles of long term therapy with Tamoxifen (Tmx). This study aimed to develop Tmx-loaded span-based nano-vesicles for delivery to malignant tissues with maximum efficacy. The effect of three variables on vesicle size (Y1), zeta potential (Y2), entrapment efficiency (Y3) and the cumulative percent release after 24 h (Y4) were optimized using Box-Behnken design. The optimized formula was prepared and tested for its stability in different storage conditions. The observed values for the optimized formula were 310.2 nm, - 42.09 mV, 75.45 and 71.70% for Y1, Y2, Y3, and Y4, respectively. The examination using electron microscopy confirmed the formation of rounded vesicles with distinctive bilayer structure. Moreover, the cytotoxic activity of the optimized formula on both breast cancer cells (MCF-7) and normal cells (BHK) showed enhanced selectivity (9.4 folds) on cancerous cells with IC50 values 4.7 ± 1.5 and 44.3 ± 1.3 µg/ml on cancer and normal cells, respectively. While, free Tmx exhibited lower selectivity (2.5 folds) than optimized nano-vesicles on cancer cells with IC50 values of 9.0 ± 1.1 µg/ml and 22.5 ± 5.3 µg/ml on MCF-7 and BHK cells, respectively. The promising prepared vesicular system, with greater efficacy and selectivity, provides a marvelous tool to overcome breast cancer treatment challenges.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias da Mama/metabolismo , Portadores de Fármacos/metabolismo , Nanopartículas/metabolismo , Tamoxifeno/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Animais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/química , Antineoplásicos Hormonais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cricetinae , Relação Dose-Resposta a Droga , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Feminino , Humanos , Células MCF-7 , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Tamoxifeno/administração & dosagem , Tamoxifeno/química , Resultado do Tratamento
5.
J Fluoresc ; 26(6): 2087-2093, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27542171

RESUMO

A sensitive and selective spectrofluorimetric method has been developed for the rapid determination of europium(III). This method is based on the formation of nonluminous complex between Eu(III) and a Schiff base reagent N, N'-bis (salicylidene)-1,2-phenylenediamine (PABD) and measuring the fluorescence quenching of Eu(III)-PABD complex at λex/em = 390/577 nm. The fluorescence intensity complex decreased linearly by increasing the Eu(III) concentration in the range of 1.0-13.0 µM. The optimum conditions for the complex formation were determined such as a pH .0 of borate buffer. The limits of detection (LOD) and quantification (LOQ) of Eu(III) were determined and found to be 0.217 and 0.653 µM, respectively. The maximum relative standard deviation of the method for an europium(III) standard of 6.0 µM was 2.07 % (n = 6). The proposed procedures could be applied successfully for the determination of the investigated metal ion in some spiked water samples with a good precision and accuracy compared to official and reported methods as revealed by t- and F-tests.

6.
BMJ Case Rep ; 17(6)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38925672

RESUMO

Multiple myeloma is a rare haematological malignancy characterised by the clonal proliferation of plasma cells within the bone marrow. Typical manifestations include bone pain, fatigue and monoclonal protein elevation in serum and urine. Less than 1% of cases develop myelomatous pleural effusion, a severe complication indicative of advanced disease and a very poor prognosis.Here, we present a case of a woman with a new diagnosis of multiple myeloma complicated by bilateral myelomatous pleural effusions as the initial presentation. This case underscores the diverse clinical spectrum of multiple myeloma, the significance of timely diagnosis and the threatening implications associated with myelomatous pleural effusions.


Assuntos
Mieloma Múltiplo , Derrame Pleural Maligno , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Feminino , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Derrame Pleural/etiologia , Derrame Pleural/diagnóstico
7.
Cureus ; 15(8): e43593, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37719507

RESUMO

Percutaneous tracheostomy (PT) is a commonly performed procedure in ICUs as a safe and cost-effective alternative to surgical tracheostomy (ST). Bronchoscopy is frequently used during PT for real-time confirmation of needle placement and tube positioning. We present a case of a 42-year-old female with a complex medical history who underwent PT and experienced acute airway loss due to endotracheal tube obstruction caused by accumulated secretions. To prevent such complications, vigilance regarding airway obstruction, cautious bronchoscope advancement, avoiding endotracheal tube puncture, and readiness to abort the procedure and replace the tube are crucial.

8.
Cureus ; 15(11): e49736, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38161902

RESUMO

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare, life-threatening condition causing significant thrombocytopenia and bleeding with the risk of developing intracerebral hemorrhage (ICH). It results from maternal immunizations against fetal platelet antigens. Here, we report a case of a pregnant patient at 30 weeks gestation who presented to the hospital with a low platelet count of 90 th/mm3 and was found to have anti-human platelet antigen (HPA) 1a, 2b antibodies. She was treated with a weekly infusion of IV immunoglobulins. However, her condition was complicated by the development of hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, which was treated promptly with a platelet transfusion and intravenous magnesium. Even though the child had severe thrombocytopenia and its associated complications, there were no signs of post-delivery thrombocytopenia or any other adverse effects. This case report highlights the importance of the antenatal management of the FNAIT to prevent severe fetal complications, such as ICH.

9.
Cureus ; 14(1): e21170, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35165619

RESUMO

Lung cancer is the leading cause of cancer death globally and in the United States. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. A progressive increase in morbidity and mortality is seen with advanced disease. Identifying specific driver mutations, such as anaplastic lymphoma kinase (ALK) mutations and directed therapy, has improved the quality of life and survival in ALK-positive NSCLC patients. Here, we present the case of a 37-year-old female who was diagnosed with stage IV NSCLC (adenocarcinoma) with a positive ALK mutation six years ago. Our case report highlights a rare ALK mutation NSCLC treated with targeted ALK inhibitor therapy. Despite having advanced-stage cancer, the treatment significantly impacted her survival with an improved quality of life.

10.
J Invest Surg ; 35(4): 814-820, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34455896

RESUMO

BACKGROUND: The second part of the duodenum is the most common part to be involved with duodenal gastrointestinal tumors (D2-GISTs). Localized resection (LR) and pancreaticoduodenectomy (PD) are two viable options for curative resection. The aim of this study is to compare the middle-term outcomes in patients with D2-GIST after either LR or PD in a single institution. PATIENTS AND METHODS: Overall, 53 patients with non-metastatic D2-GIST were analyzed. Either LR or PD was executed depending on the involvement of the ampulla of Vater. The tumors were stratified in accordance with the Miettinen classification for tumor behavior. The patients were followed up for 3 years for recurrence and survival. RESULTS: Thirty-two of the patients were females (60%) and 21 males (40%), with a mean age of 55 ± 8 years. Bleeding was the most common presentation in 19 patients (36%). LR was performed in 41 patients (77%), whereas PD was performed in 12 patients (23%). Three-year survival and recurrence were comparable between the two groups. The disease-free survival at 3 years was 85% and 92% in LR and PD group, respectively. The PD group had a significantly longer operative time and a higher incidence of postoperative pancreatic fistula. Otherwise, no statistically significant difference was calculated. A significantly shorter survival was calculated in those with a mitotic index of >5 and also for tumors classified as high grade in accordance with the Miettinen classification. 71% of those with recurrence had high mitotic index > 5/hpf. CONCLUSIONS: LR for D2-GIST is an acceptable alternative to PD with satisfactory middle-term outcomes. For tumors involving the ampulla of Vater, PD is still indicated. Furthermore, tumor biology predicts the likelihood of survival and recurrence.


Assuntos
Neoplasias Duodenais , Tumores do Estroma Gastrointestinal , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Duodeno/patologia , Duodeno/cirurgia , Feminino , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Pancreaticoduodenectomia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
11.
Cureus ; 14(5): e24980, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35719778

RESUMO

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome is a multisystem disorder. Peripheral neuropathy and monoclonal plasma cell disorder are the most common manifestations of POEMS. Although osteosclerotic or mixed sclerotic-lytic lesions are typical, osteolytic lesions are rarely encountered. We present a case of a 39-year-old male with a history of multiple endocrine disorders who presented with paresthesia, edema, and hyperpigmentation and was eventually diagnosed with POEMS syndrome. Patients with unexplained neuropathy should be evaluated for POEMS syndrome, especially when it is associated with other findings like endocrinopathy, organomegaly, skin changes, or edema.

12.
Cureus ; 14(3): e23708, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35510010

RESUMO

Immunocompromised status predisposes an individual to infection from bacteria, fungi, and viruses that are otherwise uncommon. The presence of carcinoma and the use of chemotherapy weakens one's immune system and leads to opportunistic infections of many kinds. Aspergilloma is a fungal ball that grows inside a primary cavitary lesion within the pulmonary parenchyma. Generally, immunocompromised individuals have severe and invasive infections from Aspergillus. Here, we present a case report of a female with breast carcinoma undergoing chemotherapy who previously had a lung abscess with Klebsiella. During her subsequent presentation, she was detected to have aspergilloma along with multi-drug-resistant organisms in the lung abscess along with metastasis of breast carcinoma and lung squamous cell carcinoma encapsulating the fungal ball.

13.
Cureus ; 13(8): e16871, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34513446

RESUMO

Mass vaccination campaigns are being run all over the globe to combat the ongoing COVID-19 pandemic. There have been several reports of immune thrombocytopenic purpura (ITP) occurrence following COVID-19 vaccination. However, ITP due to the Pfizer-BioNTech vaccine has been rarely reported, and a causal link has not been identified. The pathophysiology behind immune thrombocytopenia is similar to heparin-induced thrombocytopenia. The management is also similar to other secondary immune thrombocytopenia. We present a case of a 67-year old female diagnosed with immune thrombocytopenia following Pfizer-BioNTech vaccination. The treatment was resistant to high-dose steroids, intravenous immunoglobulin (IVIG), and rituximab and eventually responded to a thrombopoietin-stimulating agent.

14.
Pharmaceutics ; 13(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34834242

RESUMO

This study aimed at delivering intranasal zolmitriptan directly to the brain through preparation of bilosomes incorporated into a mucoadhesive in situ gel with extended nasal mucociliary transit time. Zolmitriptan-loaded bilosomes were constructed through a thin film hydration method applying Box-Behnken design. The independent variables were amount of sodium deoxycholate and the amount and molar ratio of cholesterol/Span® 40 mixture. Bilosomes were assessed for their entrapment efficiency, particle size and in vitro release. The optimal bilosomes were loaded into mucoadhesive in situ gel consisting of poloxamer 407 and hydroxypropyl methylcellulose. The systemic and brain kinetics of Zolmitriptan were evaluated in rats by comparing intranasal administration of prepared gel to an IV solution. Statistical analysis suggested an optimized bilosomal formulation composition of sodium deoxycholate (5 mg) with an amount and molar ratio of cholesterol/Span® 40 mixture of 255 mg and 1:7.7, respectively. The mucoadhesive in situ gel containing bilosomal formulation had a sol-gel temperature of 34.03 °C and an extended mucociliary transit time of 22.36 min. The gelling system possessed enhanced brain bioavailability compared to bilosomal dispersion (1176.98 vs. 835.77%, respectively) following intranasal administration. The gel revealed successful brain targeting with improved drug targeting efficiency and direct transport percentage indices. The intranasal delivery of mucoadhesive in situ gel containing zolmitriptan-loaded bilosomes offered direct nose-to-brain drug targeting with enhanced brain bioavailability.

15.
Cureus ; 13(10): e18526, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34765329

RESUMO

Non-small cell lung cancer (NSCLC) constitutes around 85% of lung cancer cases. Advanced non-small cell lung cancer has a poor prognosis. Immunotherapy plays a pivotal role in managing advanced non-small cell lung cancer not positive for driver mutations. Nivolumab is a monoclonal antibody against programmed death-ligand 1 (PDL1). It is approved as a second-line treatment for patients with advanced non-small cell lung cancer who progress on or after chemotherapy. We present a case of a 71-year-old female with advanced non-small cell lung cancer without any driver mutations diagnosed four years ago. Her disease progressed while on conventional chemotherapy, and she was started on nivolumab three and a half years ago. Her lung nodules resolved, she did not show signs of progression, and her performance status improved while on nivolumab. This case report highlights the current role of nivolumab in the management of NSCLC. Patients whose condition worsens while on conventional chemotherapy can respond very well to modern targeted immunotherapy.

16.
Mol Med Rep ; 21(4): 1959-1964, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32319637

RESUMO

Intimal hyperplasia (IH) is a pathologic process that leads to restenosis after treatment for peripheral arterial disease. Heat shock protein 90 (HSP90) is a molecular chaperone that regulates protein maturation. Activation of HSP90 results in increased cell migration and proliferation. 17­N­allylamino­17­demethoxygeldanamycin (17­AAG) and 17­dimethylaminoethylamino­17­demethoxygeldanamycin (17­DMAG) are low toxicity Food and Drug Association approved HSP90 inhibitors. The current study hypothesized that HSP90 inhibition was predicted to reduce vascular smooth muscle cell (VSMC) migration and proliferation. In addition, localized HSP90 inhibition may inhibit post­angioplasty IH formation. For proliferation, VSMCs were treated with serum­free media (SFM), 17­DMAG or 17­AAG. The selected proliferative agents were SFM, platelet derived growth factor (PDGF) or fibronectin. After three days, proliferation was measured. For migration, VSMCs were treated with SFM, 17­AAG or 17­DMAG with SFM, PDGF or fibronectin as chemoattractants. Balloon injury to the carotid artery was performed in rats. The groups included in the present study were the control, saline control, 17­DMAG in 20% pluronic gel delivered topically to the adventitia or intraluminal delivery of 17­DMAG. After 14 days, arteries were fixed and sectioned for morphometric analysis. Data was analyzed using ANOVA or a student's t­test. P<0.05 was considered to indicate a statistically significant difference. The results revealed that 17­AAG and 17­DMAG had no effect on cell viability. PDGF and fibronectin also increased VSMC proliferation and migration. Furthermore, both 17­AAG and 17­DMAG decreased cell migration and proliferation in all agonists. Topical adventitial treatment with 17­DMAG after balloon arterial injury reduced IH. HSP90 inhibitors suppressed VSMC proliferation and migration without affecting cell viability. Topical treatment with a HSP90 inhibitor (DMAG) decreased IH formation after arterial injury. It was concluded that 17­DMAG may be utilized as an effective therapy to prevent restenosis after revascularization.


Assuntos
Angioplastia/efeitos adversos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Túnica Íntima/patologia , Animais , Benzoquinonas/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fibronectinas/farmacologia , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Hiperplasia , Lactamas Macrocíclicas/farmacologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Ratos Sprague-Dawley
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 242: 118711, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-32738759

RESUMO

Herein, the presented manuscript provides for an extensive spectrofluorimetric method for micro determination of silver ion. This established method based on the use of the three synthesized 2,6-disubstituted pyridine derivatives (R1, R2 and R3) through exploiting their high fluorescence emission property. A noticeable effect on the fluorescence emission of the reagents after chelation with Ag (I) was monitored. Its noteworthy that the sensitivity and stability of this method was increased by using micellar medium. After chelation with Ag(I), the fluorescence emission of the ligands R1 and R2 were effectively quenched in a regular manner by increasing Ag(I) concentration. In contrast, an increase of the fluorescence intensity for reagent R3 after addition of Ag (I) was observed. The solvatochromism for all reagents under investigation was examined in different solvent. Furthermore, the chelation between Ag(I) and the and designed pyridine reagents was assessed spectrophotometrically. The optimum conditions for the most stable complexes which give a high signal difference were explored and well-determined. The linear range for determination of silver ion were determined and found to be 0.18-1.16, 0.06-0.59 and 0.18-1.43 µg mL-1 for R1, R2 and R3, respectively. The statistical analytical parameters such as LOD, LOQ, SD of slope, SD of intercept and RDS were calculated. In addition, the developed methods were efficaciously applied for determination of Ag(I) in some water samples. These selective complexation methods found to be in good precision compared to official and reported method as revealed F-test.

18.
J Clin Oncol ; 37(26): 2360-2367, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31361535

RESUMO

PURPOSE: Pemetrexed or bevacizumab is used for maintenance therapy of advanced nonsquamous non-small-cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. We conducted a randomized study to determine the optimal maintenance therapy. PATIENTS AND METHODS: Patients with advanced nonsquamous NSCLC and no prior systemic therapy received carboplatin (area under the curve, 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) for up to four cycles. Patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab (15 mg/kg), pemetrexed (500 mg/m2), or a combination of the two agents. The primary end point was overall survival, with bevacizumab serving as the control group. RESULTS: Of the 1,516 patients enrolled, 874 (57%) were randomly assigned after induction therapy to one of the three maintenance therapy groups. With a median follow-up of 50.6 months, median survival with pemetrexed was 15.9 months, compared with 14.4 months with bevacizumab (hazard ratio [HR], 0.86; P = .12); median survival with pemetrexed and bevacizumab was 16.4 months (HR, 0.9; P = .28); median progression-free survival was 4.2, 5.1 (HR, 0.85; P = .06), and 7.5 months (HR, 0.67; P < .001) for the three groups, respectively. Incidence of worst grade 3 to 4 toxicity was 29%, 37%, and 51%, respectively, for bevacizumab, pemetrexed, and the combination regimen. CONCLUSION: Single-agent bevacizumab or pemetrexed is efficacious as maintenance therapy for advanced nonsquamous NSCLC. Because of a lack of survival benefit and higher toxicity, the combination of bevacizumab and pemetrexed cannot be recommended.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/uso terapêutico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Pemetrexede/administração & dosagem , Pemetrexede/efeitos adversos , Intervalo Livre de Progressão
19.
Eur J Pharm Biopharm ; 69(3): 993-1003, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18396390

RESUMO

Although famotidine was reported to be 7.5 and 20 times more potent than ranitidine and cimetidine, respectively, its oral bioavailability is low and variable; due mainly to its poor aqueous solubility. The purpose of this study was to improve famotidine dissolution through its formulation into liquisolid systems and then to investigate the in vitro and in vivo performance of the prepared liquisolid tablets. The new mathematical model was utilized to formulate various liquisolid powder systems. Both DSC and XRD suggested loss of famotidine crystallinity upon liquisolid formulation which was further confirmed by SEM indicating that even though the drug existed in a solid dosage form, it is held within the powder substrate in a solubilized, almost molecularly dispersed state, which contributed to the enhanced drug dissolution properties. All the tested liquisolid tablet formulations showed higher drug dissolution rates (DR) than the conventional, directly compressed tables. In addition, the selected optimal formula released 78.36% of its content during the first 10 min which is 39% higher than that of the directly compressed tablets. Further, the bioavailability study indicated that the prepared optimal liquisolid formula did not differ significantly from the marketed famotidine tablets concerning Cmax, tmax, and AUC(0-8) at P<0.05.


Assuntos
Antiulcerosos/administração & dosagem , Antiulcerosos/química , Famotidina/química , Adulto , Área Sob a Curva , Disponibilidade Biológica , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Famotidina/administração & dosagem , Humanos , Masculino , Microscopia Eletrônica de Varredura , Modelos Estatísticos , Pós , Propilenoglicóis/química , Solubilidade , Comprimidos , Difração de Raios X
20.
J Pharm Sci ; 106(1): 111-122, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27544432

RESUMO

This research purposed to formulate an optimized imatinib mesylate (IM)-loaded niosomes to improve its chemotherapeutic efficacy. The influence of 3 formulation factors on niosomal vesicular size (Y1), zeta potential (Y2), entrapment capacity percentage (Y3), the percentage of initial drug release after 2 h (Y4), and the percentage of cumulative drug release after 24 h (Y5) were studied and optimized using Box-Behnken design. Optimum desirability was specified and the optimized formula was prepared, stability tested, morphologically examined, checked for vesicular bilayer formation and evaluated for its in vitro cytotoxicity on 3 different cancer cell lines namely MCF-7, HCT-116, and HepG-2 in addition to 1 normal cell line to ensure its selectivity against cancer cells. The actual responses of the optimized IM formulation were 425.36 nm, -62.4 mV, 82.96%, 18.93%, and 89.45% for Y1, Y2, Y3, Y4, and Y5, respectively. The optimized IM-loaded niosomes confirmed the spherical vesicular shape imaged by both light and electron microscopes and further proven by differential scanning calorimetry. Moreover, the optimized formula exhibited improved stability on storage at 4 ± 2°C and superior efficacy on MCF7, HCT-116, and HepG2 as IC50 values were 6.7, 16.4, and 7.3 folds less than those of free drug, respectively. Interestingly, IC50 of the optimized formula against normal cell line was ranged from 3 to 11 folds higher than in different cancer cells indicating a higher selectivity of the optimized formula to cancer cells. In conclusion, the incorporation of IM in niosomes enhanced its efficacy and selectivity toward cancer cells, presenting a promising tool to fight cancer using this approach.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Mesilato de Imatinib/administração & dosagem , Nanocápsulas/química , Adenocarcinoma/patologia , Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias do Colo/patologia , Humanos , Mesilato de Imatinib/farmacologia , Nanocápsulas/ultraestrutura , Tamanho da Partícula
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