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1.
J Orthop Res ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017392

RESUMO

Despite the success of standard antiseptic irrigation solutions in reducing periprosthetic joint infection (PJI) rates, there is still a need for more effective solutions. Synergistic use of povidone-iodine (PI) and hydrogen peroxide (H2O2) has shown promising results; however, the optimal solution concentration balancing bactericidal activity and osseointegration remains unknown. This study aims to evaluate the impact of these antiseptic irrigation solutions on osseointegration and the bone-implant interface strength in vivo. Forty C57BL/6 mice underwent bilateral tibial implantation surgery and were randomly allocated into three groups receiving 0.3% PI, 10% PI mixed with 3% H2O2, or saline as irrigation solutions intraoperatively. Assessments were performed on postoperative Days 1 and 28, including plain radiographs, microcomputed tomography (microCT) evaluation, histological analysis, immunohistochemistry, and biomechanical pull-out testing. No wound complications were observed. MicroCT scans revealed no differences in peri-implant trabecular bone parameters. Biomechanical pull-out testing showed no differences in the bone-implant interface strength across groups. Histological analysis indicated no differences in bone and bone marrow percentage areas among treatment groups. Immunohistochemical analysis demonstrated no differences among groups in peri-implant osteocalcin, osterix, or endomucin-positive cells. In conclusion, using either antiseptic irrigation solution showed no differences in osseointegration parameters compared to the control group, demonstrating safety and the absence of toxicity. CLINICAL RELEVANCE: Dilute 0.3% povidone-iodine and a 1:1 combination of 10% povidone-iodine mixed with 3% hydrogen peroxide can be safely used during primary and revision total joint arthroplasty without compromising osseointegration or causing wound complications.

2.
Nature ; 621(7979): 602-609, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37704733

RESUMO

Vertebral bone is subject to a distinct set of disease processes from long bones, including a much higher rate of solid tumour metastases1-4. The basis for this distinct biology of vertebral bone has so far remained unknown. Here we identify a vertebral skeletal stem cell (vSSC) that co-expresses ZIC1 and PAX1 together with additional cell surface markers. vSSCs display formal evidence of stemness, including self-renewal, label retention and sitting at the apex of their differentiation hierarchy. vSSCs are physiologic mediators of vertebral bone formation, as genetic blockade of the ability of vSSCs to generate osteoblasts results in defects in the vertebral neural arch and body. Human counterparts of vSSCs can be identified in vertebral endplate specimens and display a conserved differentiation hierarchy and stemness features. Multiple lines of evidence indicate that vSSCs contribute to the high rates of vertebral metastatic tropism observed in breast cancer, owing in part to increased secretion of the novel metastatic trophic factor MFGE8. Together, our results indicate that vSSCs are distinct from other skeletal stem cells and mediate the unique physiology and pathology of vertebrae, including contributing to the high rate of vertebral metastasis.


Assuntos
Neoplasias da Mama , Linhagem da Célula , Metástase Neoplásica , Coluna Vertebral , Células-Tronco , Humanos , Neoplasias da Mama/patologia , Diferenciação Celular , Autorrenovação Celular , Metástase Neoplásica/patologia , Osteoblastos/citologia , Osteoblastos/patologia , Coluna Vertebral/citologia , Coluna Vertebral/patologia , Células-Tronco/citologia , Células-Tronco/metabolismo , Células-Tronco/patologia , Biomarcadores
3.
J Orthop Surg (Hong Kong) ; 28(2): 2309499020938865, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32700655

RESUMO

PROPOSE: Total hip arthroplasty (THA) is associated with a significant risk of venous thromboembolism (VTE). Different thromboprophylaxis strategies have been used to prevent VTE. The primary aim of this study was to report the incidence of VTE and compare the efficacy and safety of rivaroxaban to enoxaparin. The secondary outcome was to report the incidence of silent deep venous thrombosis (DVT) using computed tomography venography. METHODS: One hundred sixty patients who underwent THA were enrolled in a prospective study. Patients were randomized into two groups as follows: those who received rivaroxaban 10 mg oral daily (group RXE) and those who received enoxaparin 40 IU/day subcutaneously for 14 days (group ENO). RESULTS: Both groups were matched for age, sex, comorbidities, special habits and preoperative laboratory investigations. The overall incidence of DVT was 5% (n = 8), which included four patients clinically diagnosed as having DVT and four with silent DVT. All the DVT cases occurred in veins below the knee and in the group RXE; none of the cases occurred in group ENO (p = 0.04). The incidence of DVT was significantly higher in patients with high body mass indexes (p < 0.001), older age (p = 0.024) and medical comorbidities (p = 0.14). No mortality, pulmonary embolism, stroke, wound infection or major bleeding occurred in either group. CONCLUSIONS: Among the patients who underwent hip arthroplasty, rivaroxaban prophylaxis was found to be associated with lower efficacy and similar safety outcomes as compared with enoxaparin anticoagulants.


Assuntos
Artroplastia do Joelho/efeitos adversos , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/epidemiologia , Adulto , Idoso , Anticoagulantes/uso terapêutico , Artroplastia de Quadril/métodos , Egito/epidemiologia , Enoxaparina/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Adulto Jovem
4.
J Bone Joint Surg Am ; 102(7): 543-549, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32079872

RESUMO

BACKGROUND: Male patients undergoing total joint arthroplasty have a higher risk of periprosthetic joint infection (PJI) compared with female patients. The exact reason for this finding is not well known. This study aimed to determine if patients with symptomatic benign prostatic hyperplasia (BPH) are at increased risk of PJI. METHODS: A total of 12,902 male patients who underwent primary or revision total joint arthroplasty from January 2006 to April 2017 were retrospectively identified. The mean patient age was 62.47 years and the mean patient body mass index was 30.1 kg/m. The majority of patients were Caucasian or African American. Most surgical procedures involved the hip joints (57.8%) and were primary arthroplasties (86%). Of these patients, 386 (3%) had symptomatic BPH. Among this group, 250 patients with symptomatic BPH were identified and were matched in an approximate 1:3 ratio with 708 control patients. Using the International Consensus Meeting criteria, patients who developed PJI were identified. RESULTS: The PJI rate was 7.9% in the symptomatic BPH group and 2.8% in the control group. Multivariate regression analysis in unmatched groups showed that symptomatic BPH was a strong independent risk factor for PJI. After matching for variables related to outcomes, symptomatic BPH remained a significant risk factor for PJI (p = 0.01). CONCLUSIONS: Patients with symptomatic BPH had a higher risk of PJI compared with the control patients. This may partly explain the higher rate of PJI that is seen in male patients. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Artroplastia de Substituição/efeitos adversos , Hiperplasia Prostática/complicações , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Adulto Jovem
5.
Int J Surg Case Rep ; 77: 711-715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33395881

RESUMO

INTRODUCTION: Accelerated femoral head avascular necrosis after a single dose intra-articular steroid injection is a rare pathology. Few cases were reported in the literature. Most cases were managed with total hip arthroplasty. CASE PRESENTATION: In this study, we report two rare cases of destructive osteonecrosis of the femoral head. Both patients presented with hip osteoarthritis that failed nonoperative measures. A single intra-articular corticosteroid injection was administered for each patient. Both patients had femoral head destruction and significant resorption at 14 and 11 weeks, respectively. Septic arthritis was ruled out by blood tests and joint aspiration. Total hip arthroplasty (THA) was undertaken and histology reports confirmed the osteonecrosis. The postoperative follow-up was uneventful with satisfactory hip function. DISCUSSION AND CONCLUSION: Destructive osteonecrosis of the femoral head is a rare catastrophic potential complication of intra-articular corticosteroid injection. Hence, physicians must consider this complication when counseling patients before an intra-articular corticosteroid hip injection.

6.
AAPS PharmSciTech ; 12(1): 239-47, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21225383

RESUMO

Jojoba oil-based emulgel formulations were prepared using different concentrations of various gelling agents, such as hydroxypropyl methylcellulose (HPMC) and Carbopol 934 P and combination of both. The prepared emulgels were physically evaluated for their stability after temperature cycle test, centrifugation and long-term shelf storage for 1 year at room temperature. The in vitro release at 37 °C was studied to define the effect of the concentration and type of the gelling agent. A comparison between the formulated emulgels and two commercially available products, Candistan® and Canesten® creams, was carried out to judge their efficacy and stability. The prepared emulgels exhibited non-Newtonian shear thinning behavior with little or no thixotropy. Four emulgels showed excellent stability as they demonstrated consistent rheological model under different treatment conditions. The in vitro release test showed variation in the extent of percent drug released. The drug release from the commercial preparation was lower than some of the prepared emulgel formulae. One formula containing combination of the two gelling agents (HPMC and Carbopol 934 P), showed excellent stability and high extent of clotrimazole release was microbiologically evaluated against Candida albicans using cylinder and plate method. The selected formula showed superior antimycotic activity compared to the commercially available formulation. Further in vivo animal studies for the obtained stable formula is recommended.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Clotrimazol/administração & dosagem , Clotrimazol/química , Sistemas de Liberação de Medicamentos , Acrilatos/química , Administração Tópica , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Clotrimazol/farmacocinética , Clotrimazol/farmacologia , Formas de Dosagem , Estabilidade de Medicamentos , Emulsões , Excipientes/química , Géis , Humanos , Derivados da Hipromelose , Metilcelulose/análogos & derivados , Metilcelulose/química , Viscosidade , Ceras/química
7.
Pharm Dev Technol ; 16(3): 219-27, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20163325

RESUMO

The development of rapid disintegrating tablets (RDT) requires the use of highly soluble components to support the intended use of these products. In an attempt to prepare RDT of indomethacin, its solid dispersion with polyvinyl pyrrolidone K25 (PVP) was incorporated in a fast disintegrating matrix. Drug polymer interactions were investigated using X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Indomethacin 1:1 solid dispersion with PVP was used to prepare its RDT. Two factors at 3 levels full factorial design were employed as a statistical approach to optimize the amount of superdisintegrant (Ac-di-sol) and hardness value regarding the desired disintegration and release characteristics. Drug to carrier ratio was the controlling factor for dissolution improvement. XRD and FTIR data revealed a remarkable interaction between the drug and the carrier that might be responsible for the dissolution enhancement. Multiple regression analysis revealed a significant effect of the polynomial terms for obtaining rapid disintegrating tablets. It was inferred that the hardness value is the most important factor controlling the disintegration time and the release characteristics. In conclusion, this study demonstrated that quality by design (QbD) is a potential paradigm for understanding the quality and optimizing the formulation of RDT containing indomethacin solid dispersion.


Assuntos
Portadores de Fármacos/química , Indometacina , Povidona , Química Farmacêutica , Estabilidade de Medicamentos , Dureza , Humanos , Indometacina/administração & dosagem , Indometacina/química , Cinética , Povidona/administração & dosagem , Povidona/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos/química , Difração de Raios X
8.
J Pak Med Assoc ; 60(3): 171-4, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20225770

RESUMO

OBJECTIVE: To determine the frequency of symptomatic and asymptomatic peripheral arterial disease (PAD) in patients presenting with acute coronary syndrome (ACS) at a tertiary care center in Karachi. METHODS: A total of 350 consecutive patients presenting with ACS were recruited in this cross-sectional study. All patients were enrolled from the emergency department of the National Institute of Cardiovascular Diseases (NICVD), Karachi. RESULTS: PAD, determined by presence of claudicant symptoms on interview and/or an ankle-brachial index (ABI) score less than 0.90, was present in 17.7% of patients, of whom 9.1% had no symptoms of intermittent claudication (IC) and 11.7% had no rest pain. CONCLUSIONS: Concomitant PAD is frequent among ACS patients in our study. ABI screening is simple and yields a high proportion of patients with extensive atherosclerosis who may require more aggressive atherosclerosis risk management.


Assuntos
Síndrome Coronariana Aguda/complicações , Doenças Vasculares Periféricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Estudos Transversais , Feminino , Indicadores Básicos de Saúde , Humanos , Claudicação Intermitente/etiologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Paquistão/epidemiologia , Doenças Vasculares Periféricas/diagnóstico , Doenças Vasculares Periféricas/etiologia , Fatores de Risco
9.
AAPS PharmSciTech ; 7(3): 61, 2006 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-17025242

RESUMO

The purpose of this study was to develop poly(d,l-lactic-co-glycolic acid) (PLGA)-based anastrozole microparticles for treatment of breast cancer. An emulsion/extraction method was used to prepare anastrozole sustained-release PLGA-based biodegradable microspheres. Gas chromatography with mass spectroscopy detection was used for the quantitation of the drug throughout the studies. Microparticles were formulated and characterized in terms of encapsulation efficiency, particle size distribution, surface morphology, and drug release profile. Preparative variables such as concentrations of stabilizer, drug-polymer ratio, polymer viscosity, stirring rate, and ratio of internal to external phases were found to be important factors for the preparation of anastrozole-loaded PLGA microparticles. Fourier transform infrared with attenuated total reflectance (FTIR-ATR) analysis and differential scanning calorimetry (DSC) were employed to determine any interactions between drug and polymer. An attempt was made to fit the data to various dissolution kinetics models for multiparticulate systems, including the zero order, first order, square root of time kinetics, and biphasic models. The FTIR-ATR studies revealed no chemical interaction between the drug and the polymer. DSC results indicated that the anastrozole trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. The highest correlation coefficients were obtained for the Higuchi model, suggesting a diffusion mechanism for the drug release. The results demonstrated that anastrozole microparticles with PLGA could be an alternative delivery method for the long-term treatment of breast cancer.


Assuntos
Antineoplásicos/administração & dosagem , Ácido Láctico/administração & dosagem , Nitrilas/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Polímeros/administração & dosagem , Triazóis/administração & dosagem , Anastrozol , Química Farmacêutica , Preparações de Ação Retardada , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Ácido Láctico/metabolismo , Tamanho da Partícula , Ácido Poliglicólico/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/metabolismo
10.
AAPS PharmSciTech ; 7(2): E55, 2006 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-16796372

RESUMO

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1:9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 3(2) randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug.


Assuntos
Química Farmacêutica/métodos , Portadores de Fármacos/química , Lactonas/administração & dosagem , Lactonas/química , Boca/química , Saliva/química , Sulfonas/administração & dosagem , Sulfonas/química , Comprimidos/química , Absorção , Administração Oral , Difusão , Humanos , Povidona/química , Controle de Qualidade , Solubilidade , Comprimidos/análise
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