RESUMO
OBJECTIVES: This TRIPLE study was aimed to evaluate the efficacy of polycarbophil vaginal gel (PCV) in treating symptoms of vaginal atrophy (VA) of peri- and post-menopausal women. MATERIALS AND METHODS: Sexually active women in peri- (n = 29) and post-menopause (n = 54) suffering from VA, were progressively enrolled and treated for 30 days with PCV. Those wishing to continue (n = 73) were treated for additional 180 days. PCV was administered as one application twice a week. The vaginal health index (VHI; range 5 to 25) and the visual analogue score (VAS range for 0 to 100 mm for each item) for vaginal dryness, irritation, and pain at intercourse, along with the global symptoms score (GSS; range 1 to 15) and treatment safety, were evaluated at baseline and after 30 days. In those continuing the treatment an evaluation was performed after additional 180 days. RESULTS: Women in peri and post-menopause were of 48.7 ± 3.3 years and 57.5 ± 5.7 years old., respectively. At baseline all outcomes were significantly worse (p<0.002) in postmenopausal group, except the VHI (p < 0.056). After 30 days VHI increased (p < 0.001) of 4.1 ± 0.5 (mean ± SE), and 5.1 ± 0.4 in peri- and post-menopausal women respectively. VAS of vaginal dryness decreased (p < 0.001) of -24.4 ± 3.6, and -52.7 ± 2.6 (p < 0.001), VAS of irritation decreased (p<0.001) of -18.6 ± 4.4 and -47.8 ± 3.2, VAS of pain decreased (p < 0.001) of -26.2 ± 4.3 and -55.6 ± 3.1 and the GSS decreased (p < 0.001) of -3.9 ± 0.3, and -4.9 ± 0.2, in peri and post-menopausal women, respectively. All the modifications were significantly greater (p < 0.001)(p < 0.032 for GSS) in postmenopausal women, and after 30 days all outcomes were similar in the two groups of women. In comparison to baseline, after 210 days of treatment VHI increased of 7.7 ± 0.3 (p < 0.001), VAS of vaginal dryness decreased of -53.6 ± 1.9 (p < 0.001) VAS of irritation of -42.6 ± 1.4 (p < 0.001) VAS of pain of -46.7 ± 2.3 (p < 0.001) and the GSS of -6.5 ± 0.2 ± 0.2 (p < 0.001). All outcomes improved (p < 0.001) over the values observed after 30 days of treatment (p < 0.001). No side effect was reported. CONCLUSIONS: In peri- and post-menopausal women PCV administration rapidly improves VA symptoms, and its prolongation up to 6 months further increases its efficacy.
Assuntos
Resinas Acrílicas , Atrofia , Pós-Menopausa , Vagina , Cremes, Espumas e Géis Vaginais , Doenças Vaginais , Humanos , Feminino , Atrofia/tratamento farmacológico , Cremes, Espumas e Géis Vaginais/administração & dosagem , Pessoa de Meia-Idade , Vagina/patologia , Vagina/efeitos dos fármacos , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/uso terapêutico , Doenças Vaginais/tratamento farmacológico , Doenças Vaginais/patologia , Perimenopausa , Administração Intravaginal , Resultado do Tratamento , AdultoRESUMO
We investigated the intratracheal instillation of Polyacrylic acid (PAA) in rats to determine if it would cause pulmonary disorders, and to see what factors would be associated with the pathological changes. Male F344 rats were intratracheally instilled with low (0.2â¯mg/rat) and high (1.0â¯mg/rat) doses of PAA. They were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after PAA exposure to examine inflammatory and fibrotic changes in the lungs. There was a persistent increase in the neutrophil count, lactate dehydrogenase (LDH) levels, cytokine-induced neutrophil chemoattractant (CINC) values in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Transforming growth factor-beta 1 (TGF-ß1), a fibrotic factor, showed a sustained increase in the BALF until 6 months after intratracheal instillation, and connective tissue growth factor (CTGF) in lung tissue was elevated at 3 days after exposure. Histopathological findings in the lung tissue showed persistent (more than one month) inflammation, fibrotic changes, and epithelial-mesenchymal transition (EMT) changes. There was also a strong correlation between TGF-ß1 in the BALF and, especially, in the fibrosis score of histopathological specimens. Intratracheal instillation of PAA induced persistent neutrophilic inflammation, fibrosis, and EMT in the rats' lungs, and TGF-ß1 and CTGF appeared to be associated with the persistent fibrosis.
Assuntos
Resinas Acrílicas , Líquido da Lavagem Broncoalveolar , Fator de Crescimento do Tecido Conjuntivo , Fibrose Pulmonar , Ratos Endogâmicos F344 , Fator de Crescimento Transformador beta1 , Animais , Masculino , Fator de Crescimento Transformador beta1/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Resinas Acrílicas/toxicidade , Resinas Acrílicas/administração & dosagem , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Ratos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , L-Lactato Desidrogenase/metabolismo , Heme Oxigenase-1/metabolismo , Quimiocina CXCL1/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Heme Oxigenase (Desciclizante)RESUMO
INTRODUCTION: The aim was to compare the efficacy of polyacrylate polyalcohol copolymer (PPC) injections and dextranomer/hyaluronic acid (Dx/Ha) injections for the endoscopic treatment of vesicoureteral reflux in children. MATERIAL: This retrospective cohort study included 189 young patients who had endoscopic treatment for vesicoureteral reflux from January 2012 to December 2019 in our center. Among them, 101 had PCC injections and 88 had Dx/Ha injections. Indications for treatment were vesicoureteral reflux with breakthrough urinary tract infection or vesicoureteral reflux with renal scarring on dimercaptosuccinic acid (DMSA) renal scan. Endoscopic injection was performed under the ureteral meatus. Early complications, recurrence of febrile urinary tract infection and vesicoureteral reflux after endoscopic injection, ureteral obstruction and reintervention were evaluated and compared between groups. RESULTS: Endoscopic treatment was successful in 90.1% of patients who had PPC injection and in 82% of patients who had Dx/Ha injection. Four patients presented a chronic ureteral obstruction after PPC injection, one with a complete loss of function of the dilated kidney. One patient in the Dx/Ha group presented a postoperative ureteral dilatation after 2 injections. CONCLUSION: Despite a similar success rate after PPC and Dx/Ha injections for endoscopic treatment of VUR, there may be a greater risk of postoperative ureteral obstruction after PPC injections. The benefit of using PPC to prevent febrile UTI and renal scarring in children with low-grade VUR does not seem to outweigh the risk of chronic ureteral obstruction.
Assuntos
Dextranos , Ácido Hialurônico , Obstrução Ureteral , Refluxo Vesicoureteral , Humanos , Refluxo Vesicoureteral/terapia , Estudos Retrospectivos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/uso terapêutico , Ácido Hialurônico/efeitos adversos , Feminino , Masculino , Dextranos/uso terapêutico , Dextranos/administração & dosagem , Dextranos/efeitos adversos , Pré-Escolar , Resultado do Tratamento , Lactente , Resinas Acrílicas/uso terapêutico , Resinas Acrílicas/administração & dosagem , Criança , Injeções , Estudos de Coortes , Ureteroscopia/efeitos adversosRESUMO
OBJECTIVE: There are few effective osteoarthritis (OA) therapies. A novel injectable polyacrylamide hydrogel (iPAAG) previously demonstrated efficacy and safety up to week 26 in an open-label study of knee OA. Here we report longer-term effectiveness and safety data. METHODS: This multi-centre, open-label study included patients with symptomatic and radiographic knee OA. Primary outcome was WOMAC pain (0-100 scale) at 13 weeks, and patients continued to 26 weeks before entering a further 26-week extension phase. Secondary efficacy outcomes included WOMAC stiffness and function subscales, Patient Global Assessment (PGA) and proportion of OMERACT-OARSI responders. Safety outcomes were adverse events (AEs). RESULTS: 49 participants (31 women, mean age 70) received an ultrasound-guided, intra-articular injection of 6 ml iPAAG; 46 completed the extension phase to 52 weeks. There was a significant reduction in the WOMAC pain score from baseline to 52 weeks (- 17.7 points (95% CI - 23.1; - 12.4); p < 0.0001). Similar sustained improvements were observed for WOMAC stiffness (11.0 points; 95% CI - 17.0; - 4.9), physical function (18.0 points; 95% CI - 19.1; - 10.6), and PGA (16.3 points; 95% CI - 23.1; - 9.4). At 52 weeks 62.2% of patients were OMERACT-OARSI responders. From 26 to 52 weeks, 8 adverse effects (AE), including 1 serious AE (cerebrovascular accident) were reported in 5 subjects. None of the new adverse events were thought to be device related. CONCLUSION: This open-label study suggests persistent benefits and safety of iPAAG through 52 weeks after a single injection. TRIAL REGISTRATION: Clinicaltrials.gov NCT04179552.
Assuntos
Resinas Acrílicas , Osteoartrite do Joelho , Humanos , Feminino , Osteoartrite do Joelho/tratamento farmacológico , Resinas Acrílicas/administração & dosagem , Masculino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Seguimentos , Injeções Intra-Articulares , Fatores de Tempo , Hidrogéis/administração & dosagem , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints. ANIMALS: 8 healthy horses. METHODS: In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% PAHG (Noltrex Vet; Nucleus ProVets LLC) and contralateral 0.9% saline control on days 0, 45, 90, and 135. Treatment and control joints were randomly assigned. Synovial fluid was collected before administration of 4% PAHG or 0.9% saline on day 0 and at study completion for cellular and biomarker evaluation. Serial physical and lameness examinations were performed throughout the study. On day 240, gross examination and harvest of cartilage and synovial membrane for histology were completed. RESULTS: There were no histologic changes in articular cartilage or synovial fluid biomarkers. The 4% PAHG was seen on the surface of the synovium in 5 of 8 treated joints 105 days after the last treatment. There are minimal effects following serial injections of 4% PAHG on normal joints in horses following administration at 0, 45, 90, and 135 days, with final evaluation on day 240. CLINICAL RELEVANCE: Serial administration of intra-articular 4% PAHG in horses may provide long-term joint lubrication with no detrimental effects.
Assuntos
Resinas Acrílicas , Biomarcadores , Líquido Sinovial , Animais , Cavalos , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/química , Resinas Acrílicas/administração & dosagem , Injeções Intra-Articulares/veterinária , Feminino , Masculino , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/patologia , Coxeadura Animal/induzido quimicamente , Membrana Sinovial/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Osteoartrite/veterinária , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Articulações/efeitos dos fármacos , Articulações/patologiaRESUMO
Myocardial ischemia-reperfusion injury (MIRI) significantly contributes to the high incidence of complications and mortality associated with acute myocardial infarction. Recently, injectable electroconductive hydrogels (IECHs) have emerged as promising tools for replicating the mechanical, electroconductive, and physiological characteristics of cardiac tissue. Herein, we aimed to develop a novel IECH by incorporating irbesartan as a drug delivery system (DDS) for cardiac repair. Our approach involved merging a conductive poly-thiophene derivative (PEDOT: PSS) with an injectable dual-network adhesive hydrogel (DNAH) comprising a catechol-branched polyacrylamide network and a chitosan-hyaluronic acid covalent network. The resulting P-DNAH hydrogel, benefitting from a high conducting polymer content, a chemically crosslinked network, a robust dissipative matrix, and dynamic oxidation of catechol to quinone exhibited superior mechanical strength, desirable conductivity, and robust wet-adhesiveness. In vitro experiments with the P-DNAH hydrogel carrying irbesartan (P-DNAH-I) demonstrated excellent biocompatibility by cck-8 kit on H9C2 cells and a rapid initial release of irbesartan. Upon injection into the infarcted hearts of MIRI mouse models, the P-DNAH-I hydrogel effectively inhibited the inflammatory response and reduced the infarct size. In conclusion, our results suggest that the P-DNAH hydrogel, possessing suitable mechanical properties and electroconductivity, serves as an ideal IECH for DDS, delivering irbesartan to promote heart repair.
Assuntos
Resinas Acrílicas , Quitosana , Hidrogéis , Traumatismo por Reperfusão Miocárdica , Irbesartana/administração & dosagem , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Quitosana/administração & dosagem , Quitosana/química , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Hidrogéis/toxicidade , Condutividade Elétrica , Elasticidade , Injeções , Linhagem Celular , Animais , Ratos , Modelos Animais de Doenças , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Sobrevivência Celular/efeitos dos fármacosRESUMO
BACKGROUND: Discoid lupus erythematosus (DLE) is an autoimmune disease with multifactor etiology which develops in genetically susceptible patients. Rarely, DLE lesions can mimic other connective tissue disorders such as morphea. The growing application of soft tissue fillers is associated with increasing complications. Some substances used for soft tissue augmentation such as silicon implants may trigger lupus erythematosus diseases. CASE REPORT: Here we report a case of morphea-like discoid lupus erythematosus developed several years after polyacrylamide dermal filler (PAAG) injection for facial rejuvenation. CONCLUSION: As noninvasive procedures like dermal filler injections are increasing worldwide, physicians may consider the long-term probable side effects of these compounds.
Assuntos
Resinas Acrílicas , Preenchedores Dérmicos , Lúpus Eritematoso Discoide , Humanos , Lúpus Eritematoso Discoide/diagnóstico , Lúpus Eritematoso Discoide/induzido quimicamente , Preenchedores Dérmicos/efeitos adversos , Preenchedores Dérmicos/administração & dosagem , Feminino , Resinas Acrílicas/efeitos adversos , Resinas Acrílicas/administração & dosagem , Esclerodermia Localizada/induzido quimicamente , Esclerodermia Localizada/diagnóstico , Técnicas Cosméticas/efeitos adversos , Pessoa de Meia-IdadeRESUMO
This study was conducted to evaluate the effect of polyacrylamide (PAM) supplementation on the intake, digestion, weight gain, metabolism and growth of lambs. A total of ten 30 days old male small-tailed Han lambs with a body weight of 7.7±0.5 kg were divided into two equal groups (n = 5 each) and fed a basal diet or diet supplemented with 2.0 g of PAM per kg diet. The duration of the experiment was 210 days and experimental diets were fed ad libitum throughout the experimental period. Voluntary feed intake (VFI) was measured on daily basis, while body weight was measured on every ten days of the experiment.Two digestive and metabolic trials were conducted at the lamb's age of 95 to 103 days (Trial 1) and at the age of 210 to 218 days (Trial 2). At the end of experiment, all lambs were slaughtered to determine carcass characteristics. Results of the current study showed that supplementation of PAM in the diet of lambs increased the VFI and daily body gain by 14.4% (P < 0.05) and 15.2% (P < 0.01), respectively. In Trial 1, PAM supplementation in the diet increased the digestibility of dry matter (DM), organic matter (OM), crude protein (CP), cellulose, energy, and nitrogen retention by 7.9%, 5.4%, 6.4%, 9.6%, 4.3% and 30.3% (P < 0.01), respectively, and in Trial 2, PAM supplementation in the diet increased the digestibility of DM, OM, CP, cellulose, energy, and nitrogen retention by 9.3%, 7.9%, 7.7%, 11.6%, 6.9% and 38.5% (P < 0.01), respectively. Results of carcass parameter explored that supplementation of PAM in the diet increased the carcass, net meat and lean meat weights by 24.5%, 25.5%, and 30.6% (P < 0.01), respectively, however, PAM supplementation in the diet did not influence the contents of DM, OM, or CP in fresh liver, leg muscle, and rumen tissue; in addition, the CP contents in the Longissimus dorsi muscle was decreased by the supplementation of PAM in the diet. In summary, supplementation of 2.0 g of PAM per kg diet increased the VFI, nutrient digestibility, nitrogen retention, and carcass yield of lambs.
Assuntos
Resinas Acrílicas , Ração Animal , Suplementos Nutricionais , Animais , Masculino , Ração Animal/análise , Peso Corporal , Celulose/farmacologia , Dieta/veterinária , Digestão/efeitos dos fármacos , Digestão/fisiologia , Ingestão de Alimentos , Nitrogênio/metabolismo , Nutrientes , Rúmen/metabolismo , Ovinos/metabolismo , Carneiro Doméstico/metabolismo , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/uso terapêuticoRESUMO
Protein affinity reagents that specifically and strongly bind to target molecules are widely used in disease detection, diagnosis, and therapy. Although antibodies and their fragments are the gold standard in protein-protein inhibitors (PPIs), synthetic polymers such as linear polymers, dendrimers, and nanoparticles as cost-effective PPIs have attracted great attention as alternatives to antibodies. These polymers exhibit high affinity to the target by imitating natural protein-protein interactions. However, only a few in vivo applications have been reported. Here, our recent advances in the development of synthetic polymers for in vivo application are reviewed. Poly(N-isopropylacrylamide) (pNIPAm) was used as a model of synthetic affinity reagents. Incorporation of both sulfated carbohydrate and hydrophobic monomers into lightly crosslinked pNIPAm nanoparticles (NPs) captured and neutralized vascular endothelial growth factor (VEGF) and inhibited tumor growth upon intravenous injection into tumor-bearing mice. Modification of a liposome with the pNIPAm-based linear polymer increased the polymer circulation time after intravenous injection and improved the affinity for the target. The pNIPAm-based NPs delivered by oral administration captured the target small molecules and inhibited their absorption from the intestine. Our recent findings provide useful information for the design of synthetic polymers that capture target molecules in vivo.
Assuntos
Resinas Acrílicas , Desenho de Fármacos/métodos , Terapia de Alvo Molecular/métodos , Nanopartículas , Polímeros , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/química , Resinas Acrílicas/metabolismo , Resinas Acrílicas/farmacologia , Administração Oral , Animais , Humanos , Interações Hidrofóbicas e Hidrofílicas , Indicadores e Reagentes , Injeções Intravenosas , Lipossomos , Camundongos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Polímeros/administração & dosagem , Polímeros/química , Polímeros/metabolismo , Polímeros/farmacologia , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
The goal of this study was to develop and examine the nanogel-based topical delivery system of mupirocin. Nanogels were prepared with chitosan and bovine serum albumin by ionic gelation and Carbopol 940 was added to improve the gelling/adhesive properties. Detailed characterization studies were performed and the cellular binding capacity of radiolabeled nanogels was investigated on CCD-1070Sk cell lines. Results indicate the successful formation of nanogels with particle size and zeta potential ranged between 341.920-603.320 nm and 13.120-24.300 mV, respectively. The mechanical and rheological studies proved pseudoplastic and strong elastic gel behavior (G' > G''). Mupirocin was successfully entrapped into nanogels with a ratio of more than 95% and the loaded drug was slowly released up to 93.89 ± 3.07% within 24 h. The ex vivo penetration and permeation percentages of mupirocin were very low (1.172 ± 0.202% and 0.161 ± 0.136%) indicating the suitability of nanogels for dermal use against superficial skin infections. The microbiological studies pointed out the effectiveness of nanogels against Staphylococcus aureus strains. Nanogels did not show toxicity signs and the cell binding capacity of radiolabeled formulations was found to be higher than [99mTc]NaTcO4 to CCD-1070Sk cell line. Overall, mupirocin nanogels might be considered as a potential and safe topical treatment option for bacterial skin infections.
Assuntos
Antibacterianos/administração & dosagem , Mupirocina/administração & dosagem , Nanogéis , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/química , Administração Cutânea , Antibacterianos/farmacocinética , Quitosana/administração & dosagem , Quitosana/química , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Humanos , Mupirocina/farmacocinética , Nanogéis/administração & dosagem , Nanogéis/química , Permeabilidade , Compostos Radiofarmacêuticos , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacosRESUMO
A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0-96 for the nanofibers was 9-20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.
Assuntos
Resinas Acrílicas/química , Administração Oftálmica , Quitosana/química , Nanofibras/química , Ofloxacino/química , Álcool de Polivinil/química , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/farmacocinética , Animais , Antibacterianos/química , Química Farmacêutica/métodos , Quitosana/administração & dosagem , Quitosana/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Nanofibras/administração & dosagem , Ofloxacino/administração & dosagem , Ofloxacino/farmacocinética , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/farmacocinética , Coelhos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
BACKGROUND: This is a updated version of our Cochrane Review published in Issue 6, 2012. Sexually-transmitted infections (STIs) continue to rise worldwide, imposing an enormous morbidity and mortality burden. Effective prevention strategies, including microbicides, are needed to achieve the goals of the World Heath Organization (WHO) global strategy for the prevention and control of these infections. OBJECTIVES: To determine the effectiveness and safety of topical microbicides for preventing acquisition of STIs, including HIV. SEARCH METHODS: We undertook a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CLIB, Web of Science, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and reference lists of relevant articles up to August 2020. In addition, we contacted relevant organisations and experts. SELECTION CRITERIA: We included randomised controlled trials of vaginal microbicides compared to placebo (except for nonoxynol-9 because it is covered in related Cochrane Reviews). Eligible participants were sexually-active non-pregnant, WSM and MSM, who had no laboratory confirmed STIs. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies, extracted data, and assessed risks of bias in duplicate, resolving differences by consensus. We conducted a fixed-effect meta-analysis, stratified by type of microbicide, and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included eight trials from the earlier version of the review and four new trials, i.e. a total of 12 trials with 32,464 participants (all WSM). We did not find any eligible study that enrolled MSM or reported fungal STI as an outcome. We have no study awaiting assessment. All 12 trials were conducted in sub-Saharan Africa, with one having a study site in the USA, and another having a site in India. Vaginal microbicides tested were BufferGel and PRO 2000 (1 trial, 3101 women), Carraguard (1 trial, 6202 women), cellulose sulphate (2 trials, 3069 women), dapivirine (2 trials, 4588 women), PRO 2000 (1 trial, 9385 women), C31G (SAVVY) (2 trials, 4295 women), and tenofovir (3 trials, 4958 women). All microbicides were compared to placebo and all trials had low risk of bias. Dapivirine probably reduces the risk of acquiring HIV infection: risk ratio (RR) 0.71, (95% confidence interval (CI) 0.57 to 0.89, I2 = 0%, 2 trials, 4588 women; moderate-certainty evidence). The other microbicides may result in little to no difference in the risk of acquiring HIV (low-certainty evidence); including tenofovir (RR 0.83, 95% CI 0.68 to 1.02, cellulose sulphate (RR 1.20, 95% CI 0.74 to 1.95, BufferGel (RR 1.05, 95% CI 0.73 to 1.52), Carraguard (RR 0.89, 95% CI 0.71 to 1.11), PRO 2000 (RR 0.93, 95% CI 0.77 to 1.14), and SAVVY (RR 1.38, 95% CI 0.79 to 2.41). Existing evidence suggests that cellulose sulphate (RR 0.99, 95% CI 0.37 to 2.62, 1 trial, 1425 women), and PRO 2000 (RR 0.95, 95% CI 0.73 to 1.23) may result in little to no difference in the risk of getting herpes simplex virus type 2 infection (low-certainty evidence). Two studies reported data on tenofovir's effect on this virus. One suggested that tenofovir may reduce the risk (RR 0.55, 95% CI 0.36 to 0.82; 224 participants) while the other did not find evidence of an effect (RR 0.94, 95% CI 0.85 to 1.03; 1003 participants). We have not reported the pooled result because of substantial heterogeneity of effect between the two studies (l2 = 85%). The evidence also suggests that dapivirine (RR 1.70, 95% CI 0.63 to 4.59), tenofovir (RR 1.27, 95% CI 0.58 to 2.78), cellulose sulphate (RR 0.69, 95% CI 0.26 to 1.81), and (Carraguard (RR 1.07, 95% CI 0.75 to 1.52) may have little or no effect on the risk of acquiring syphilis (low-certainty evidence). In addition, dapivirine (RR 0.97, 95% CI 0.89 to 1.07), tenofovir (RR 0.90, 95% CI 0.71 to 1.13), cellulose sulphate (RR 0.70, 95% CI 0.49 to 0.99), BufferGel (RR 0.97, 95% CI 0.65 to 1.45), Carraguard (RR 0.96, 95% CI 0.83 to 1.12), and PRO 2000 (RR 1.01, 95% CI 0.84 to 1.22) may result in little to no difference in the risk of acquiring chlamydia infection (low-certainty evidence). The evidence also suggests that current topical microbicides may not have an effect on the risk of acquiring gonorrhoea, condyloma acuminatum, trichomoniasis, or human papillomavirus infection (low-certainty evidence). Microbicide use in the 12 trials, compared to placebo, did not lead to any difference in adverse event rates. No study reported on acceptability of the intervention. AUTHORS' CONCLUSIONS: Current evidence shows that vaginal dapivirine microbicide probably reduces HIV acquisition in women who have sex with men. Other types of vaginal microbicides have not shown evidence of an effect on acquisition of STIs, including HIV. Further research should continue on the development and testing of new microbicides.
Assuntos
Anti-Infecciosos Locais/administração & dosagem , Infecções Sexualmente Transmissíveis/prevenção & controle , Resinas Acrílicas/administração & dosagem , Adenina/administração & dosagem , Adenina/análogos & derivados , Administração Intravaginal , Agaricales/química , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Viés , Celulose/administração & dosagem , Celulose/efeitos adversos , Celulose/análogos & derivados , Feminino , Infecções por HIV/prevenção & controle , Humanos , Naftalenossulfonatos/administração & dosagem , Placebos/administração & dosagem , Polímeros/administração & dosagem , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Alga Marinha/química , Tenofovir/administração & dosagem , Tenofovir/efeitos adversosRESUMO
PURPOSE: To evaluate the safety and efficacy of 2 locoregional therapies (LRTs) including hepatic artery embolization (HAE) and transarterial radioembolization (TARE) in the treatment of patients with metastatic ovarian cancer to the liver. MATERIAL AND METHODS: From October 2010 to May 2019, the data of 15 consecutive patients (median age, 54 years ± 9.8; range, 35-78 years) with hepatic metastatic ovarian cancer who were treated with either HAE (n = 6; 40%) or TARE (n = 9; 60%) were reviewed. The most common histopathologic type was epithelial ovarian carcinoma (80%). The most common chemotherapy regimens used prior to embolization included carboplatin, paclitaxel, cisplatin, and bevacizumab. Patients received a mean of 4 lines ± 3 (range, 1-9) of chemotherapy. All patients with serous carcinoma were resistant to platinum at the time of embolization. Indications for embolization were progression of disease to the liver while receiving chemotherapy in 14 (93.3%) patients and palliative pain control in 1 patient. RESULTS: The overall response rates at 1, 3, and 6 months were 92.4%, 85.6%, and 70%, respectively. Median overall survival from the time of LRT was 9 (95% confidence interval [CI], 4-14) months. Median local tumor progression was 6.4 months ± 5.03 (95% CI, 3.3-9.5). No grade 3-5 adverse events were detected in either group. CONCLUSIONS: HAE and TARE were well tolerated in patients with metastatic ovarian cancer to the liver and possibly ensured prolonged disease control in heavily treated, predominantly in patients resistant to platinum. Larger numbers are needed to verify these data.
Assuntos
Resinas Acrílicas/administração & dosagem , Embolização Terapêutica , Gelatina/administração & dosagem , Artéria Hepática , Neoplasias Hepáticas/terapia , Neoplasias Ovarianas/terapia , Compostos Radiofarmacêuticos/administração & dosagem , Resinas Acrílicas/efeitos adversos , Adulto , Idoso , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Gelatina/efeitos adversos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Cidade de Nova Iorque , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Tamanho da Partícula , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de TempoRESUMO
PURPOSE: To evaluate the safety and efficacy of superior rectal artery embolization (SRAE) with different-sized tris-acryl gelatin microspheres in symptomatic hemorrhoidal disease (HD). MATERIALS AND METHODS: Forty-two patients (male, 30; female, 12; median age, 45 years) with symptomatic HD (2 grade I, 8 grade II, 17 grade III, and 15 grade IV) were divided into 3 experimental arms (500-700 µm, 700-900 µm, and 900-1,200 µm groups; each had 14 patients) in a prospective randomized style to perform SRAE. Follow-up was performed by rectoscopy, clinical examination, and questionnaires. The primary outcome measure was the clinical success rate at 12 months. Secondary outcome measures were technical success rate, recurrence rate, procedure-related mortality, procedure-related complications, and any outcome changes between particle sizes. RESULTS: No procedure-related deaths or major morbidities were observed. There was a 54% minor complication rate (n = 23/42) in the treated zone: 45% sustained small superficial ulcerations (n = 19/42), 7% small rectosigmoid junction ulcerations (n = 3/42), and 2% small fibrotic scar tissue (n = 1/42). The clinical success rate was 93%. Of the groups, the best French bleeding score decrease was obtained in the 900-1,200 µm group. There were improvements in the quality of life score and visual analogue scale score after the SRAE procedure, although not in the Goligher score. No recurrent disease was observed. CONCLUSIONS: SRAE with tris-acryl gelatin microspheres for symptomatic HD is a safe and efficient treatment, with results favoring the use of larger microspheres.
Assuntos
Resinas Acrílicas/administração & dosagem , Artérias , Embolização Terapêutica , Hemorragia Gastrointestinal/terapia , Gelatina/administração & dosagem , Hemorroidas/terapia , Reto/irrigação sanguínea , Resinas Acrílicas/efeitos adversos , Adolescente , Adulto , Idoso , Embolização Terapêutica/efeitos adversos , Feminino , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Gelatina/efeitos adversos , Hemorroidas/complicações , Hemorroidas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Estudos Prospectivos , Qualidade de Vida , Recidiva , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento , Turquia , Adulto JovemRESUMO
PURPOSE: To develop and characterize a porcine model of liver cancer that could be used to test new locoregional therapies. MATERIALS AND METHODS: Liver tumors were induced in 18 Oncopigs (transgenic pigs with Cre-inducible TP53R167H and KRASG12D mutations) by using an adenoviral vector encoding the Cre-recombinase gene. The resulting 60 tumors were characterized on multiphase contrast-enhanced CT, angiography, perfusion, micro-CT, and necropsy. Transarterial embolization was performed using 40-120 µm (4 pigs) or 100-300 µm (4 pigs) Embosphere microspheres. Response to embolization was evaluated on imaging. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy. RESULTS: Liver tumors developed at 60/70 (86%) inoculated sites. Mean tumor size was 2.1 cm (range, 0.3-4 cm) at 1 week. Microscopically, all animals developed poorly differentiated to undifferentiated carcinomas accompanied by a major inflammatory component, which resembled undifferentiated carcinomas of the human pancreatobiliary tract. Cytokeratin and vimentin expression confirmed epithelioid and mesenchymal differentiation, respectively. Lymph node, lung, and peritoneal metastases were seen in some cases. On multiphase CT, all tumors had a hypovascular center, and 17/60 (28%) had a hypervascular rim. After transarterial embolization, noncontrast CT showed retained contrast medium in the tumors. Follow-up contrast-enhanced scan showed reduced size of tumors after embolization using either 40-120 µm or 100-300 µm Embosphere microspheres, while untreated tumors showed continued growth. CONCLUSIONS: Liver tumors can be induced in a transgenic pig and can be successfully treated using bland embolization.
Assuntos
Resinas Acrílicas/administração & dosagem , Embolização Terapêutica , Gelatina/administração & dosagem , Neoplasias Hepáticas/terapia , Resinas Acrílicas/toxicidade , Animais , Animais Geneticamente Modificados , Linhagem Celular , Modelos Animais de Doenças , Embolização Terapêutica/efeitos adversos , Gelatina/toxicidade , Genes p53 , Genes ras , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Sus scrofa/genética , Fatores de Tempo , Carga Tumoral , Microtomografia por Raio-XAssuntos
Abscesso/cirurgia , Resinas Acrílicas/efeitos adversos , Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/efeitos adversos , Drenagem/métodos , Abscesso/diagnóstico , Abscesso/etiologia , Resinas Acrílicas/administração & dosagem , Bochecha/diagnóstico por imagem , Bochecha/cirurgia , Preenchedores Dérmicos/administração & dosagem , Humanos , Injeções Subcutâneas/efeitos adversos , Tela Subcutânea/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Tough hydrogels with the ability to be repeatedly processed into various shapes as thermoplastics are highly desired in advanced medical devices and tissue engineering. Here, we have developed a kind of versatile supramolecular hydrogel with a network cross-linked by double hydrogen bonds from poly(N-acryloyl glycinamide) (PNAGA). The resulting PNAGA-30 hydrogels (30 wt% solid content) are tough, re-processable, and recyclable similar to thermoplastics. The hydrogels in the form of fragments can be easily re-processed into various shapes including sheet, filament, cylinder and other complex shapes by using simple stamping and injection methods. The mechanical properties of the re-programed hydrogels are comparable to the properties of the original hydrogels. The re-processability and robust mechanical properties of the PNAGA hydrogels are promising for practical applications in soft materials, tissue engineering and wearable devices. Furthermore, the PNAGA-30&LiCl ionic hydrogels can be fabricated by simply compositing LiCl into thermoplastic hydrogels. The PNAGA-30&LiCl hydrogels can function as multifunctional strain sensors to monitor large human movements and tiny vibrations, thereby showing great application potential in robotics, biomedical prosthetics, personal healthcare monitoring and so on.
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Resinas Acrílicas/síntese química , Reutilização de Equipamento , Hidrogéis/síntese química , Engenharia Tecidual/métodos , Dispositivos Eletrônicos Vestíveis , Resinas Acrílicas/administração & dosagem , Humanos , Hidrogéis/administração & dosagem , Estresse MecânicoRESUMO
PURPOSE: To compare the outcomes of prostatic artery embolization (PAE) in patients with different intravesical prostatic protrusion (IPP) grades. MATERIALS AND METHODS: This retrospective single-center study included 128 patients (aged 50-86 years) who underwent PAE from 2013 to 2017. IPP grades were classified as follows: grade I (<10 mm), grade II (10-19 mm), and grade III (≥20 mm). Nineteen patients (14.8%) had grade I [mean IPP 7.8 mm, prostatic volume (PV) 64.1 cm3], 77 (60.2%) had grade II (mean IPP 14.9 mm, PV 87.0 cm3), and 32 (25%) had grade III (mean IPP 26.2 mm, PV 132.6 cm3), P < .01. The outcomes, including PV, international prostate symptom score (IPSS), and quality of life (QoL), were compared between the IPP grades at the 12-month follow-up. Clinical failure was defined as IPSS >7 or QoL >2. RESULTS: IPP decreased (I: -8.2%, II: -27.3%, and III: -38.7%, P = .01), and all other endpoints improved (P < .01). Adjusted covariance analysis, considering baseline PV as a confounding factor, showed no correlation between the 12-month outcomes and baseline IPP. Clinical failure was observed in 17/128 patients (13.3%) and was similar in prevalence among the IPP groups (P = .20). Minor complications occurred in 43 patients (33.6%) and major in 3 (2.3%). There were statistical differences in the complications between IPP grades II and III (P < .01). CONCLUSIONS: PAE was similarly effective in all the IPP grades at the 12-month follow-up, and there was no difference in the clinical failure between the groups. Complications in IPP grade III were more frequent than those in IPP grade II.
Assuntos
Resinas Acrílicas/administração & dosagem , Artérias , Embolização Terapêutica , Gelatina/administração & dosagem , Sintomas do Trato Urinário Inferior/terapia , Próstata/irrigação sanguínea , Hiperplasia Prostática/terapia , Resinas Acrílicas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Artérias/diagnóstico por imagem , Embolização Terapêutica/efeitos adversos , Gelatina/efeitos adversos , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico por imagem , Sintomas do Trato Urinário Inferior/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/fisiopatologia , Qualidade de Vida , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do Tratamento , UrodinâmicaRESUMO
BACKGROUND: Anatomical segmentectomy is more and more widely used in lung nodules and early stage lung cancer. Postoperative lung air leakage is one of the common complications after surgery. This study aimed to explore the effect of the application of repair materials in precise segmentectomy under thoracoscopy in reducing postoperative lung air leakage. METHODS: This study included patients admitted to the Department of Thoracic Surgery of Jiangsu Provincial People's Hospital who were scheduled to undergo thoracoscopic segmentectomy from August 1, 2018 to July 31, 2019. According to the difference of the materials used in the treatment of the inter-segment interface during the operation: patients who used microporous polysaccharide hemostatic powder+fibrin adhesive glue+absorbable polyglycolic acid patch were divided into group A, and the patients with fibrin adhesive+absorbable polyglycolic acid patch were divided into group B. The preoperative basic information of all patients and the daily postoperative chest drainage volume, the indwelling time of the chest drainage tube, the chest radiograph before the chest drainage tube is removed, the chest radiograph after the chest drainage tube is removed, blood routine and postoperative hospital stay were collected and recorded, and the effect of the application of intraoperative repair materials on postoperative lung air leakage was analyzed. RESULTS: There were statistically significant differences in the indwelling time of thoracic drainage tube (P=0.019) and postoperative hospital stay (P=0.017) between the two groups. CONCLUSIONS: Compared with the use of the fibrin glue+absorbability polyglycolic acid patch, the use of microporous polysaccharide hemostatic powder+fibrin glue+absorbability polyglycolic acid patch in the treatment of the inter-segment interface during segmentectomy can better reduce the incidence of postoperative air leakage and shorten the postoperative hospital stay.
Assuntos
Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Pneumotórax/terapia , Complicações Pós-Operatórias/terapia , Resinas Acrílicas/administração & dosagem , Adulto , Tubos Torácicos , Drenagem , Feminino , Humanos , Pulmão/fisiopatologia , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Pneumotórax/etiologia , Polissacarídeos/administração & dosagem , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Induction of protective mucosal T cell memory remains a formidable challenge to vaccinologists. Using a combination adjuvant strategy that elicits potent CD8 and CD4 T cell responses, we define the tenets of vaccine-induced pulmonary T cell immunity. An acrylic-acid-based adjuvant (ADJ), in combination with Toll-like receptor (TLR) agonists glucopyranosyl lipid adjuvant (GLA) or CpG, promotes mucosal imprinting but engages distinct transcription programs to drive different degrees of terminal differentiation and disparate polarization of TH1/TC1/TH17/TC17 effector/memory T cells. Combination of ADJ with GLA, but not CpG, dampens T cell receptor (TCR) signaling, mitigates terminal differentiation of effectors, and enhances the development of CD4 and CD8 TRM cells that protect against H1N1 and H5N1 influenza viruses. Mechanistically, vaccine-elicited CD4 T cells play a vital role in optimal programming of CD8 TRM and viral control. Taken together, these findings provide further insights into vaccine-induced multifaceted mucosal T cell immunity with implications in the development of vaccines against respiratorypathogens, including influenza virus and SARS-CoV-2.