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Dimenhydrinate (DMH)-loaded buccal bioadhesive films for the prevention and treatment of motion sickness were prepared and optimized. This study examines the rate of drug release from the films for prolonged periods of time to reduce or limit the frequency of DMH administration. Based on preliminary studies using various polymers and concentrations, hydroxyethylcellulose (2.5, 3.0, and 3.2%), and xanthan gum (2.8%) were chosen as matrix polymers. The films were analyzed with respect to their mechanical, physicochemical, bioadhesive, swelling, and in-vitro release properties. In in-vivo pharmacokinetic studies, xanthan gum-based DMH buccal film was associated with significantly increased DMH plasma levels between 1 h and 5 h after DMH dosing when compared with an oral drug solution. The area under the curve AUC0-7 h value of the mucoadhesive buccal film was two-fold higher than the oral DMH solution. Histological analysis revealed that DMH films cause mild morphological and inflammatory changes in rabbit buccal mucosa. The DMH buccal film is effective for approximately 7 h, thus representing an option for single-dose antiemetic therapy. This dosage regimen could be particularly beneficial for chain travelers who travel for long periods of time.
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Adesivos/administração & dosagem , Adesivos/química , Dimenidrinato/administração & dosagem , Dimenidrinato/química , Mucosa Bucal/metabolismo , Administração Bucal , Animais , Área Sob a Curva , Disponibilidade Biológica , Celulose/análogos & derivados , Celulose/química , Química Farmacêutica/métodos , Dimenidrinato/farmacocinética , Masculino , Polissacarídeos Bacterianos/química , Coelhos , Propriedades de SuperfícieRESUMO
CONTEXT/OBJECTIVE: The addition of chemical enhancers into formulations is the most commonly employed approach to overcome the skin barrier. The objective of this work was to evaluate the effect of vehicle and chemical enhancers on the skin permeation and accumulation of terbinafine, an allylamine antifungal drug. METHODS: Terbinafine (1% w/w) was formulated as a Carbopol 934 P gel formulation in presence and absence of three chemical enhancers, nerolidol, dl-limonene and urea. Terbinafine distribution and deposition in stratum corneum (SC) and skin following 8-h ex vivo permeation study was determined using a sequential tape stripping procedure. The conformational order of SC lipids was investigated by ATR-FTIR spectroscopy. RESULTS AND DISCUSSION: Nerolidol containing gel formulation produced significantly higher enhancement in terbinafine permeation through skin and its skin accumulation was increased. ATR-FTIR results showed enhancer induced lipid bilayer disruption in SC. Urea resulted in enhanced permeation of terbinafine across the skin and a balanced distribution to the SC was achieved. But, dl-limonene could not minimize the accumulation of terbinafine in the upper SC. CONCLUSION: Nerolidol dramatically improved the skin permeation and deposition of terbinafine in the skin that might help to optimize targeting of the drug to the epidermal sites as required for both of superficial and deep cutaneous fungal infections.
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Antifúngicos/administração & dosagem , Naftalenos/administração & dosagem , Veículos Farmacêuticos/farmacologia , Absorção Cutânea/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo , Administração Cutânea , Animais , Antifúngicos/farmacocinética , Cicloexenos/farmacologia , Limoneno , Naftalenos/farmacocinética , Permeabilidade/efeitos dos fármacos , Sesquiterpenos/farmacologia , Suínos , Terbinafina , Terpenos/farmacologia , Ureia/farmacologiaRESUMO
PURPOSE: Recent studies have suggested that positron emission tomography (PET) imaging with (68)Ga-labelled DOTA-somatostatin analogues (SST) like octreotide and octreotate is useful in diagnosing neuroendocrine tumours (NETs) and has superior value over both CT and planar and single photon emission computed tomography (SPECT) somatostatin receptor scintigraphy (SRS). The aim of the present study was to evaluate the role of (68)Ga-DOTA-1-NaI(3)-octreotide ((68)Ga-DOTANOC) in patients with SST receptor-expressing tumours and to compare the results of (68)Ga-DOTA-D-Phe(1)-Tyr(3)-octreotate ((68)Ga-DOTATATE) in the same patient population. METHODS: Twenty SRS were included in the study. Patients' age (n = 20) ranged from 25 to 75 years (mean 55.4 ± 12.7 years). There were eight patients with well-differentiated neuroendocrine tumour (WDNET) grade1, eight patients with WDNET grade 2, one patient with poorly differentiated neuroendocrine carcinoma (PDNEC) grade 3 and one patient with mixed adenoneuroendocrine tumour (MANEC). All patients had two consecutive PET studies with (68)Ga-DOTATATE and (68)Ga-DOTANOC. All images were evaluated visually and maximum standardized uptake values (SUV(max)) were also calculated for quantitative evaluation. RESULTS: On visual evaluation both tracers produced equally excellent image quality and similar body distribution. The physiological uptake sites of pituitary and salivary glands showed higher uptake in (68)Ga-DOTATATE images. Liver and spleen uptake values were evaluated as equal. Both (68)Ga-DOTATATE and (68)Ga-DOTANOC were negative in 6 (30 %) patients and positive in 14 (70 %) patients. In (68)Ga-DOTANOC images only 116 of 130 (89 %) lesions could be defined and 14 lesions were missed because of lack of any uptake. SUV(max) values of lesions were significantly higher on (68)Ga-DOTATATE images. CONCLUSION: Our study demonstrated that the images obtained by (68)Ga-DOTATATE and (68)Ga-DOTANOC have comparable diagnostic accuracy. However, (68)Ga-DOTATATE seems to have a higher lesion uptake and may have a potential advantage.
Assuntos
Imagem Multimodal/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Compostos Organometálicos , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/metabolismo , Receptores de Somatostatina/metabolismo , Estudos RetrospectivosRESUMO
In COVID-19-induced acute respiratory distress syndrome, the lungs are incapable of filling with sufficient air, leading to hypoxemia that results in high mortality among hospitalized patients. In clinical trials, low-molecular-weight heparin was administered via a specially designed soft-mist inhaler device in an investigator initiated, single-center, open-label, phase-IIb clinical trial. Patients with evidently worse clinical presentations were classed as the "Device Group"; 40 patients were given low-molecular-weight heparin via a soft mist inhaler at a dose of 4000 IU per administration, twice a day. The Control Group, also made up of 40 patients, received the standard therapy. The predetermined severity of hypoxemia and the peripheral oxygen saturation of patients were measured on the 1st and 10th days of treatment. The improvement was particularly striking in cases of severe hypoxemia. In the 10-day treatment, low-molecular-weight heparin was shown to significantly improve breathing capability when delivered via a soft-mist inhaler.
RESUMO
The lack of a well defined nanosystem that retains its physicochemical properties and can be tracked in complex biological environments is one reason why the study of NP transport across biological barriers is currently so difficult. As a result, surprisingly little is known about the fate of sub-micron particles once they deposit in the airways of the lung. The aim of this study was to design and manufacture a novel nanoparticle (NP) core that would be physically stable, i.e., not aggregate in biological fluids, and act as a tracking system to investigate NP distribution in the lung. Accordingly, covalent fluorescent labeling (to allow particle tracking) of 40% hydrolyzed poly(vinyl alcohol) was undertaken by inducing dissociation of the carboxylic acid group (ArCOO(-)) of 5(6)-carboxyfluorescein (CF) which then reacted with the hydroxyl group of poly(vinyl alcohol) (PVA) to produce a covalently linked PVA-CF ester. Polymer purification was followed by NP manufacture and characterization in biological media. In contrast to commercial latex particles which aggregated in both cell culture medium and Hank's balanced salt solution (HBSS), the PVA nanoparticles retained their original size (ca. 220 nm), maintained a neutral surface charge in cell culture medium for 24 h and were not acutely toxic to respiratory cells in vitro.
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Nanopartículas/administração & dosagem , Material Particulado/administração & dosagem , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/farmacocinética , Administração por Inalação , Linhagem Celular , Humanos , Nanopartículas/química , Material Particulado/química , Álcool de Polivinil/químicaRESUMO
The objectives of this study were to develop matrix-type transdermal patches of verapamil hydrochloride (VRP) with pectin as a matrix polymer to investigate the influence of several terpenes on in vitro permeation of VRP through rat skin and to evaluate pharmacodynamic activity of transdermal formulations in rats. Matrix-type transdermal patches containing VRP were prepared using pectin as a matrix agent and propylene glycol as a plasticizer agent. Terpenes such as nerolidol, d-limonene, eucalpytol, menthone, and menthol were also used as a chemical enhancer to improve the skin penetration of VRP. The permeation studies were performed using Franz-type diffusion cells and full-thickness excised abdominal rat skin. Effects of terpenes on the permeation parameters of VRP were evaluated. In vitro skin permeation studies showed that nerolidol was the most promising enhancer among the enhancers examined in the present study, followed by d-limonene. Pharmacodynamic activity of the transdermal patches containing nerolidol or d-limonene was evaluated in rats by the measurement of systolic blood pressure for 360 min with the use of the tail cuff method. VRP transdermal patches significantly decreased the systolic blood pressure after 30 min and transdermal patches containing nerolidol and d-limonene maintained the decrease in blood pressure during the observation of 360 min.
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Bloqueadores dos Canais de Cálcio/farmacocinética , Excipientes/química , Verapamil/farmacocinética , Administração Cutânea , Animais , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/farmacologia , Feminino , Técnicas In Vitro , Masculino , Pectinas/química , Ratos , Ratos Wistar , Pele/metabolismo , Absorção Cutânea , Terpenos/química , Fatores de Tempo , Verapamil/administração & dosagem , Verapamil/farmacologiaRESUMO
The aim of this study was to design and evaluate of mucoadhesive gel formulations for the vaginal application of clomiphene citrate (CLM) for local treatment of human papilloma virus (HPV) infections. Chitosan (CHI) and polycarbophil (PC) were covalently modified using the thioglycolic acid and L-cysteine, respectively. The formation of thiol conjugates of chitosan (CHI-TG) and polycarbophil (PC-CYS) were confirmed by FT-IR analysis and PC-CYS and CHI-TG were found to have 148.42 +/- 4.16 and 41.17 +/- 2.34 micromol of thiol groups per gram of polymer, respectively. One percent CLM gels were prepared by combination of various concentrations of PC and CHI with thiolated conjugates of these polymers. Hardness, compressibility, elasticity, adhesiveness and cohesiveness of the gels were measured by Texture profile analysis and the vaginal mucoadhesion was investigated by mucoadhesion test. The increasing in the amount of the thiol conjugates was found to enhance the elasticity, cohesiveness, adhesiveness and mucoadhesion of the gel formulations but not their hardness and compressibility when compared to gels prepared using their respective parent formulations. Slower release rate of CLM from gels was achieved when the polymer concentrations were increased in the gel formulations. PC and its thiol conjugate were found to prolong the release of CLM longer than 70 h unlike gel formulations prepared using CHI and its thiol conjugate which were able to release CLM up to 12 h. Stability of CLM was preserved during the 3 month stability analysis under controlled room temperature and accelerated conditions.
Assuntos
Resinas Acrílicas/química , Adesivos/química , Quitosana/química , Polímeros/química , Compostos de Sulfidrila/química , Cremes, Espumas e Géis Vaginais/química , Resinas Acrílicas/farmacocinética , Adesivos/farmacocinética , Química Farmacêutica , Quitosana/farmacocinética , Força Compressiva , Condiloma Acuminado/tratamento farmacológico , Condiloma Acuminado/virologia , Relação Dose-Resposta a Droga , Humanos , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/crescimento & desenvolvimento , Polímeros/farmacocinética , Compostos de Sulfidrila/farmacocinética , Cremes, Espumas e Géis Vaginais/farmacocinéticaRESUMO
PURPOSE: Upon diagnosis, distant metastases are encountered in 21-50% of neuroendocrine tumours (NETs). However, few systemic treatment options are available for the well-differentiated NETs in the metastatic stage. Lu-DOTATATE is one of the most effective treatments in this limited patient group. We retrospectively investigated its efficacy and effect on the survival in patients with both well-differentiated and grade III NETs who had high uptake in pretherapeutic Ga-DOTATATE PET/computed tomography scans. PATIENTS AND METHODS: Patients with metastatic NETs treated with Lu-DOTATATE between January 2010 and November 2015 in our department were included in this retrospective cohort. Toxicity and adverse effects were evaluated according to SWOG criteria. Progression-free survival (PFS) and overall survival (OS) rates were calculated considering the first date of treatment. Response was evaluated according to RECIST criteria. Potential predictors of survival and response were analysed. RESULTS: Patients (n=186) with metastatic NETs originating from various primary sites (bronchial, pancreatic, nonpancreatic gastroenteropancreatic-NETs, pheochromocytoma-paraganglioma and unknown primary) were treated with 1107 courses of Lu-DOTATATE treatment (median: 6; range: 3-12). Among 160 patients whose responses to treatment could be evaluated according to the RECIST criteria, 28.1% (n=45) had a progressive disease, 21.9% (n=35) had a stable disease, 46.9% (n=75) had a partial response and 3.1% (n=5) had a complete response. Median follow-up was 30.6 months. The Kaplan-Meier estimated median PFS was 36.4 months, mean PFS was 38 months and the mean OS was 55 months. The disease control rates in patients with WHO grades I, II and III were 74, 73 and 60%, respectively, and the OS rates were 61.9, 52.2 and 38.4 months, respectively. We observed no major renal toxicity except a minor increase (11.1%) in average serum creatinine levels. In 33.9% (n=56) of the patients, grade I toxicity; in 9.1% (n=15), grade II; and in 1.2% (n=2), grade III toxicity were observed. CONCLUSION: Lu-DOTATATE therapy is an important treatment option in somatostatin receptor type-2-positive pancreatic, nonpancreatic gastroenteropancreatic-NETs, and lung NETs including metastatic NETs with an unknown primary site and significantly contributed to patients' OS. Additionally, peptide receptor radionuclide therapy may have a role in a selected subgroup of patients with grade III NET with high somatostatin receptor type-2 expression.
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Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
68Ga-PSMA-11 PET/CT has been proven to have high clinical value for imaging of prostate cancer and rapidly gained popularity. In this study, we aimed to investigate absorbed doses of 68Ga-PSMA-11. Seven patients (mean age = 66.9 ± 6.6 years, range: 57-79 years) were enrolled in the study. Whole body PET images were acquired with multiple time points. MIRD method, NUKFIT and OLINDA/EXM software were used for dosimetry calculations. Kidneys, bladder wall, salivary and lacrimal glands received the highest absorbed dose. Estimated absorbed doses to these organs after injection of 150 MBq 68Ga-PSMA-11 were 37.0, 12.6, 14.4 and 6.3 mSv, respectively. Effective dose from PET scanning with 150 MBq injected 68Ga-PSMA-11 was 2.5 mSv. In conclusion, 68Ga-PSMA-11 has a favorable dosimetry profile similar to the 68Ga labeled octreotide analogs, which are used safely in routine clinical practices for many years. No adverse effects were reported. The kidneys were the dose-limiting organs.
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Ácido Edético/análogos & derivados , Oligopeptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Radiometria/métodos , Dosagem Radioterapêutica , Idoso , Carga Corporal (Radioterapia) , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Rim/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Software , Imagem Corporal TotalRESUMO
The purpose of this study was to design novel colon specific drug delivery system containing flurbiprofen (FLB) microsponges. Microsponges containing FLB and Eudragit RS 100 were prepared by quasi-emulsion solvent diffusion method. Additionally, FLB was entrapped into a commercial Microsponge 5640 system using entrapment method. Afterwards, the effects of drug:polymer ratio, inner phase solvent amount, stirring time and speed and stirrer type on the physical characteristics of microsponges were investigated. The thermal behaviour, surface morphology, particle size and pore structure of microsponges were examined. The colon specific formulations were prepared by compression coating and also pore plugging of microsponges with pectin:hydroxypropylmethyl cellulose (HPMC) mixture followed by tabletting. In vitro dissolution studies were done on all formulations and the results were kinetically and statistically evaluated. The microsponges were spherical in shape, between 30.7 and 94.5microm in diameter and showed high porosity values (61-72%). The pore shapes of microsponges prepared by quasi-emulsion solvent diffusion method and entrapment method were found as spherical and cylindrical holes, respectively. Mechanically strong tablets prepared for colon specific drug delivery were obtained owing to the plastic deformation of sponge-like structure of microsponges. In vitro studies exhibited that compression coated colon specific tablet formulations started to release the drug at the 8th hour corresponding to the proximal colon arrival time due to the addition of enzyme, following a modified release pattern while the drug release from the colon specific formulations prepared by pore plugging the microsponges showed an increase at the 8th hour which was the time point that the enzyme addition made. This study presents a new approach based on microsponges for colon specific drug delivery.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Colo/metabolismo , Sistemas de Liberação de Medicamentos , Flurbiprofeno/administração & dosagem , Algoritmos , Anti-Inflamatórios não Esteroides/química , Composição de Medicamentos , Desenho de Fármacos , Emulsões , Flurbiprofeno/química , Cinética , Nanopartículas , Tamanho da Partícula , Porosidade , Comprimidos com Revestimento EntéricoRESUMO
In this study, heparin-loaded microspheres having smooth surface and small particle size were designed in order to provide the absorption of heparin through nasal mucosa. For this purpose, microspheres at different polymer/drug ratios (1:10, 1:2.5 and 1:1) and at different concentrations of polyvinyl alcohol, emulsifying agent (1.5% and 2.5% w/v) were prepared by solvent evaporation method with poly(lactic acid). The microspheres were for evaluated shape and surface properties, particle size, production yield, encapsulation efficiency and in vitro drug release. Based on the in vitro data, selected microspheres were applied by nasal route to Wistar albino rats. According to in vivo studies, heparin-loaded microspheres may be used by nasal route as an alternative to parenteral route.
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Anticoagulantes/administração & dosagem , Anticoagulantes/farmacocinética , Heparina/administração & dosagem , Heparina/farmacocinética , Microesferas , Administração Intranasal , Animais , Disponibilidade Biológica , Coagulação Sanguínea/efeitos dos fármacos , Preparações de Ação Retardada , Emulsificantes/química , Feminino , Ácido Láctico/química , Mucosa Nasal/metabolismo , Tempo de Tromboplastina Parcial , Tamanho da Partícula , Poliésteres , Polímeros/química , Álcool de Polivinil/química , Ratos , Ratos Wistar , Solubilidade , Propriedades de Superfície , TemperaturaRESUMO
PURPOSE: The aim of the study was to evaluate the diagnostic value of the prostate-specific membrane antigen (PSMA) ligand (68)Ga-HBED-CC (PSMA PET/CT) in patients with prostate cancer and evaluate the value of early imaging of the pelvis. MATERIALS AND METHODS: The files of 28 patients were retrospectively evaluated. All patients had a histopatological confirmation of prostate cancer. PSMA PET/CT images were obtained at 5 and 60 min after injection from all patients. RESULTS: Intense pathologic radiotracer uptake was observed in 23 patients (77%) at the site of primary tumour. Lymph node metastases were detected in 10 patients (36%) and bone metastases were detected in seven patients (25%). Bone scan (n=25) results revealed metastatic bone lesions in four patients, equivocal results in nine patients and normal results in 12 patients. PSMA PET/CT confirmed bone metastases in all four patients. Pathologic radiotracer uptake in PSMA PET/CT scans was observed only in one patient among those who had equivocal bone scans. PSMA PET/CT showed additional bone lesions in two patients who had a normal bone scan. When we compared early and late pelvic images we found no difference in the number of lesions detected. The maximum standardized uptake value (SUV(max)) for primary tumour, lymph nodes and bone metastases was significantly higher in late images. CONCLUSION: PSMA PET/CT imaging seems to be a valuable imaging modality for evaluation of primary prostate cancer and it seems to have potential for the detection of lymph node and bone metastases. Early images 5 min p.i. can help to better distinguish between urinary bladder (before tracer accumulation occurs) and tumour lesions.
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Antígenos de Superfície/metabolismo , Ácido Edético/análogos & derivados , Glutamato Carboxipeptidase II/metabolismo , Pelve/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Ácido Edético/metabolismo , Humanos , Ligantes , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Recidiva , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Somatostatin receptor (Sstr) scintigraphy with radiolabelled somatostatin analogues has been used extensively for the diagnosis and therapy of Sstr-expressing tumours. It has been shown that well-differentiated thyroid cancer (WDTC) cells have a high expression of Sstr2, Sstr3 and Sstr5. Hence, WDTC cells could be an ideal target for the evaluation of lesion uptake of Ga-68 DOTA-1-NaI3-octreotide (DOTA-NOC), which has a high affinity not only to Sstr2 but also to Sstr3 and Sstr5. The aim of the present study was to evaluate the value of Ga-68 DOTA-NOC as a target for Sstr2-expressing, Sstr3-expressing and Sstr5-expressing tumours in WDTC patients and to compare the results with those of Ga-68 DOTA-TATE in the same patient population. METHOD: Thirteen patients with WDTC were included in our study: nine with papillary thyroid cancer, three with Hurthle cell carcinoma and one with follicular thyroid carcinoma. All patients had elevated serum thyroglobulin levels and negative post-therapeutic I-131 whole-body scans, which were obtained after the last radioiodine treatment. All patients had undergone two consecutive PET imaging studies with Ga-68 DOTA-D-Phe1-Tyr3-octreotate (DOTA-TATE) and Ga-68 DOTA-NOC, respectively. All images were evaluated visually, and maximum standardized uptake values were calculated. RESULTS: Both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET images gave comparable results. Among the 13 patients, imaging with both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC gave negative results in five (38%) patients and positive results in eight (62%) patients. A total of 45 lesions were identified on Ga-68 DOTA-TATE images and 42 on Ga-68 DOTA-NOC images; three lesions were missed. Lesion uptake was significantly higher on Ga-68 DOTA-TATE images. Maximum standardized uptake values of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC were 12.9±9.1 and 6.3±4.1 (n=54, P<0.001), respectively. CONCLUSION: Our study suggested that Ga-68 DOTA-TATE has a higher lesion uptake even in WDTC patients and may have potential advantage over Ga-68 DOTA-NOC.
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Adenocarcinoma Folicular/diagnóstico por imagem , Carcinoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adenoma Oxífilo , Adulto , Idoso , Antineoplásicos Hormonais , Carcinoma Papilar , Feminino , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida , Compostos Organometálicos , Compostos Radiofarmacêuticos , Câncer Papilífero da TireoideRESUMO
INTRODUCTION: Recent studies have suggested that PET imaging with Ga-68-labelled DOTA-somatostatin analogues such as octreotide and octreotate is useful in diagnosing neuroendocrine tumours (NETs) and has superior value over both computed tomography and planar and SPECT somatostatin receptor scintigraphy. PURPOSE: The aim of the present study was to evaluate the role of Ga-68 DOTA-lanreotide (Ga-68-DOTA-LAN) in patients with somatostatin receptor (sst)-expressing tumours and to compare the results of Ga-68 DOTA-D-Phe1-Tyr3-octreotate (Ga-68-DOTA-TATE) in the same patient population. MATERIALS AND METHODS: Twelve patients with NETs who were referred to our department for somatostatin receptor scintigraphy were included in the study. There were four patients with well-differentiated neuroendocrine tumour (WDNET) grade 1, two patients with WDNET grade 2, and three patients with poorly differentiated neuroendocrine carcinoma (PDNEC) grade 3. There was also one patient with medullary thyroid cancer, one patient with meningioma and one patient with MEN-1. All patients underwent two consecutive PET imaging studies with Ga-68-DOTA-TATE and Ga-68 DOTA-LAN. All images were evaluated visually, and maximum standardized uptake value was calculated for quantitative evaluation. RESULTS: On visual examination of maximum intensity projection images, GA-68 DOTA-LAN was seen to have high background activity and high bone marrow uptake. Both tracers defined 67 lesions. Ga-68 DOTA-TATE images revealed 63 (94%) clearly defined lesions, missing four lesions. In contrast, Ga-68 DOTA-LAN images defined only 23 (44%) lesions, missing 44 (56%) lesions. Thirty-two bone lesions were detected on Ga-68-DOTA-TATE images. Among them, only 11 (34%) were positive on Ga-68 DOTA-LAN images, whereas 21 (66%) were negative. When we evaluated liver, mediastinum and gastrointestinal tract lesions, Ga-68 DOTA-LAN was seen to be positive for 12 (34%) lesions and negative for 23 (66%) lesions. CONCLUSION: Although the results are preliminary, the image quality obtained by Ga-68-DOTA-TATE seems to be superior to that obtained by Ga-68 DOTA-LAN. With its significantly higher lesion uptake and higher ability to detect lesions, Ga-68-DOTA-TATE seems to be a better radioligand compared with Ga-68-DOTA-LAN for the diagnosis of NETs.
Assuntos
Compostos Heterocíclicos com 1 Anel , Imagem Multimodal/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Compostos Organometálicos , Peptídeos Cíclicos , Tomografia por Emissão de Pósitrons/métodos , Somatostatina/análogos & derivados , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/metabolismo , Receptores de Somatostatina/metabolismoRESUMO
Inhaled heparin appears to provide benefit in the management of airway hyper-reactivity and inflammation. The pharmacodynamics of inhaled heparin are however transient. Providing sustained heparin concentrations in the respiratory tract should provide for an extended duration of action. We examined the in-vivo efficacy of a nebulised controlled-release microparticle formulation of heparin in modifying antigen-induced airway hyper-reactivity (AHR) and lung inflammation. Heparin-loaded biodegradable poly (D,L-lactide-co-glycolide) microparticles were prepared by spray-drying. Aerosol properties for both nebulised heparin solution and heparin microparticles displayed characteristics consistent with heparin delivery to the respiratory tract. In vitro release assays showed heparin to be released from the microparticles over 8-12 h and for the heparin to remain functional. Temporal pharmacodynamic responses were studied in an ovalbumin-sensitised in vivo model exhibiting AHR and airway inflammation. Despite a reduced total dose of heparin deposited in the airways following nebulisation with heparin microparticles, this treatment led to a more sustained inhibitory effect upon AHR and airway inflammation than equivalent doses of nebulised heparin solution. The work supports extended-release heparin as an inhalation dosing strategy in experimental therapeutic applications aimed at improving the pharmacodynamics of heparin in the treatment of AHR and lung inflammation.
Assuntos
Hiper-Reatividade Brônquica/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Heparina/administração & dosagem , Pneumonia/tratamento farmacológico , Administração por Inalação , Animais , Antígenos , Hiper-Reatividade Brônquica/induzido quimicamente , Preparações de Ação Retardada , Portadores de Fármacos/química , Cobaias , Heparina/química , Ácido Láctico/química , Pulmão/metabolismo , Masculino , Nebulizadores e Vaporizadores , Ovalbumina , Pneumonia/induzido quimicamente , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , SoluçõesRESUMO
Our purpose was to compare the efficacy of 25 microg and 50 microg intravaginally administered misoprostol tablets for cervical ripening and labor induction. Either 25-microg (n: 58) or 50-microg (n: 56) misoprostol tablets were randomly administered intravaginally to 114 subjects with an unripe cervix for labor induction. The physician was blinded to the medication. Intravaginal misoprostol was given every 4 h until the onset of labor. The mean Bishop score before misoprostol administration was 2.1 +/- 1.6 in the 25-microg group and 2.0 +/- 1.4 in the 50-microg group (p > 0.05). With the 25-microg dose the time until delivery was significantly longer (991.2 +/- 514.4 min vs. 703.12 +/- 432.6 min in the 50-microg group). The use of oxytocin augmentation was significantly higher in the 25-microg group (63.8%) than the 50-microg group (32.1%; p < 0.05). The proportions of patients with tachysystoles and hypersystoles were not significantly different between the two groups (19 and 6.9%, respectively, in the 25-microg group and 25 and 17.8%, respectively, in 50-microg group; p > 0.05). Overall, in the 25-microg group more women achieved vaginal delivery (79.3 vs. 60.7%; p < 0.05). The rate of cesarean sections due to non-reassuring fetal status was higher in the 50-microg misoprostol group (28.6 vs. 10.3%; p < 0.05). The number of neonates with a low 1-min Apgar score (<7) was significantly higher in the 50-microg misoprostol group (26.8 vs. 8.6%; p < 0.05), but 5-min Apgar scores and umbilical artery blood gas values at the time of delivery were not significantly different between the groups (p > 0.05). One patient in the 25-microg group suffered a ruptured uterus. Intravaginal administration of 25 microg of misoprostol is a clinically effective labor induction regimen and has the least adverse effects and complications.