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1.
J Shoulder Elbow Surg ; 32(11): 2207-2213, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37276919

RESUMO

BACKGROUND: Biomechanical testing of abduction moment arms presents a useful method to assess the contributions of individual rotator cuff muscles to glenohumeral function. This study aimed to investigate the changes in abduction moment arms after the treatment of supraspinatus tears with superior capsular reconstruction (SCR), bursal acromial reconstruction (BAR), and a combined SCR-BAR procedure, all with human dermal allograft. METHODS: We tested 7 fresh-frozen cadaveric specimens under 6 conditions: (1) intact, (2) 50% supraspinatus tear (partial tear), (3) 100% supraspinatus tear, (4) SCR, (5) SCR combined with BAR, and (6) BAR. In each condition, the moment arms for the individual muscles of the teres minor, subscapularis, and infraspinatus were calculated throughout 90° of abduction using a motion capture system. Analysis of variance and post hoc Tukey testing were performed to determine significance. RESULTS: In the teres minor, the moment arms in the SCR (11.9 mm), BAR (10.1 mm), and SCR-BAR (11.9 mm) conditions were greater than those in the intact (8.5 mm; P = .001, P = .001, and P = .001, respectively), partial tear (9.1 mm; P = .001, P = .128, and P = .001, respectively), and complete tear (8.8 mm; P = .001, P = .011, and P = .001, respectively) conditions. Similarly, in the subscapularis, the moment arms in the SCR (13.4 mm), BAR (13.8 mm), and SCR-BAR (13.5 mm) conditions were greater than those in the intact (10.6 mm; P = .006, P = .001, and P = .003, respectively) and partial tear (10.4 mm; P = .006, P = .001, and P = .003, respectively) conditions. In the teres minor, the SCR (11.9 mm) and SCR-BAR (11.9 mm) conditions were also found to have significantly increased moment arms compared with the BAR condition (10.1 mm; P = .001 and P = .001, respectively). In the infraspinatus, the BAR condition (13.8 mm) was found to have a significantly decreased moment arm compared with the partial tear condition (15.8 mm, P = .026), with no other significant findings between conditions. CONCLUSION: Our results suggest that the moment arm contributions of the individual muscles comprising the rotator cuff can change after reconstruction to compensate for tears. SCR and SCR-BAR increase the moment arms in the teres minor and subscapularis, potentially allowing for increased abduction ability.

2.
J Wound Care ; 32(Sup5): S6-S10, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37121665

RESUMO

OBJECTIVE: The objective of the current study was to evaluate outcomes of elective knee arthroscopy portal closure comparing two skin closure techniques. METHOD: This was a randomised controlled trial including healthy volunteers aged ≥18 years undergoing elective knee arthroscopy that used two portals. At the time of surgery, each patient's two arthroscopy portal closures were randomised to one of two closure techniques; the first technique used approximation of the skin with a micro-anchor skin dressing (BandGrip Inc., US), while the second closure technique used an absorbable suture (Biosyn Monofilament, Medtronic) and a liquid bonding agent skin closure (Dermabond, Ethicon Inc., US). Postoperative complications and patient-reported outcomes were evaluated at the first visit after knee arthroscopy and at six weeks postoperatively. RESULTS: A total of 38 patients (76 portals) were enrolled in this study. No patients reported wound complications of either portal; thus, there was no significant difference (p>0.05) in wound complication rates between the skin closure techniques. Survey questions regarding any difference in appearance and cosmesis between the closure techniques' portal sites were responded to by 15 patients, all of whom indicated no difference in appearance between the portal sites. There was also no statistically significant difference between the two closure techniques with regards to appearance. CONCLUSION: There was no significant difference in presence of wound complications or appearance between skin closure with the micro-anchor skin dressing and the absorbable suture/liquid bonding agent skin closure.


Assuntos
Artroscopia , Articulação do Joelho , Humanos , Adolescente , Adulto , Articulação do Joelho/cirurgia , Complicações Pós-Operatórias , Técnicas de Fechamento de Ferimentos , Bandagens
3.
Sports Health ; 15(1): 105-110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35081842

RESUMO

CONTEXT: In-season glenohumeral instability is a common clinical dilemma faced by physicians who care for athletes. Both nonoperative and operative management of athletes with in-season glenohumeral instability have been well described. Functional bracing remains less understood as a treatment modality. This review aims to provide an update on the most recent literature regarding the use of functional bracing for shoulder instability. EVIDENCE ACQUISITION: MEDLINE (PubMed and Ovid platforms), Web of Science, Embase, and Cochrane Database of Systemic Reviews were searched for articles available in English through June 1, 2021. The search terms shoulder brace, shoulder instability, athlete, in-season, glenohumeral instability, anterior shoulder instability, posterior shoulder instability, and bracing were used. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 3. RESULTS: Research on the clinical outcomes of functional bracing remains mixed for patients with shoulder instability. Two studies have demonstrated improved return to play with functional bracing, while 1 study demonstrated no difference in return to play between braced athletes and nonbraced athletes with anterior instability. One previous study demonstrated that prophylactic use of bilateral shoulder stabilizing braces significantly decreased time lost due to injury in athletes with posterior instability. Previous biomechanical studies have demonstrated improved proprioception with brace wear as well as successful limitation of active shoulder range of motion. CONCLUSION: Bracing in athletes with shoulder instability remains an important nonoperative treatment modality. While clinical benefits are yet to be validated through high-quality studies, preliminary results suggest a potential benefit to recovery, with minimal downsides. Nevertheless, the use of bracing remains an individual choice but is especially recommended in settings of high-risk sports for shoulder instability, such as football.


Assuntos
Futebol Americano , Instabilidade Articular , Luxação do Ombro , Lesões do Ombro , Articulação do Ombro , Humanos , Luxação do Ombro/cirurgia , Instabilidade Articular/cirurgia , Ombro , Estações do Ano , Lesões do Ombro/terapia , Atletas , Volta ao Esporte , Recidiva
4.
Eur J Orthop Surg Traumatol ; 33(2): 353-360, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35088146

RESUMO

PURPOSE: The purpose of this study was to investigate length of stay, postoperative mobilization and discharge disposition following intramedullary nailing of ballistic femoral shaft fractures stratified by nailing technique. METHODS: All adult patients with isolated ballistic femoral shaft fractures between May 1, 2018, and September 1, 2021, were reviewed. The final cohort included 69 ballistic femur fractures in 69 patients. Of the 69 patients included, 29 were treated with retrograde nailing while 40 were treated with antegrade nailing. RESULTS: The average length of stay of patients treated with antegrade nailing was 2.55 days (SD 1.3 days) compared with 3.45 days (SD 2.3 days) for patients treated with retrograde nailing; this was statistically significant (P = 0.04). Median steps on POD1 for antegrade nailing were 20 and 8 for retrograde. There was no significant difference in VAS pain scores between the two cohorts. All patients were discharged home. CONCLUSION: The average length of stay for patients who underwent antegrade nailing was significantly shorter when compared with the retrograde nailing. Patients in the antegrade cohort mobilized further than the retrograde cohort in the immediate postoperative setting. We found no significant difference in VAS pain scores between the two cohorts.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Adulto , Humanos , Fixação Intramedular de Fraturas/efeitos adversos , Tempo de Internação , Consolidação da Fratura , Fraturas do Fêmur/cirurgia , Fraturas do Fêmur/etiologia , Dor/etiologia , Pinos Ortopédicos , Resultado do Tratamento , Estudos Retrospectivos
5.
Eur J Orthop Surg Traumatol ; 33(4): 851-856, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35129680

RESUMO

OBJECTIVE: The purpose of this study was to describe the frequency of nerve injury associated with lower extremity ballistic trauma, the associated skeletal and soft tissue injuries, and the rate of neurologic recovery. DESIGN AND SETTING: A retrospective review of an institutional trauma database was completed at a single level 1 trauma academic medical center. PATIENTS: This was an institutional review board approved retrospective cohort study of patients over 16 years of age presenting with ballistic-related traumatic injury to the lower extremities between May 2018 and May 2019. All patients identified with lower extremity ballistic trauma were included in this study. The rate of nerve palsy, associated skeletal injury, and operative fixation were recorded for each anatomic zone. Rates of associated concomitant vascular injury, fracture, and compartment syndrome were collected through a review of the electronic medical records. Chart review was performed to evaluate outcomes and nerve recovery. RESULTS: Twenty-one patients (21 extremities, 21/148, 14%) were diagnosed by attending physicians, fellowship-trained in orthopedic trauma, as having ballistic-related nerve injuries. Seventy-three percent of patients with a documented neurologic injury (11/15) demonstrated complete nerve recovery as measured by the MRC and sensory scale assessment at most recent follow-up, while the rest demonstrated no improvement in their neurologic deficits from presentation. The rate of associated vascular injury in patients with lower extremity nerve palsies was 38% (8/21). While the rate of vascular injury in the absence of neurologic injury was 3% (4/127). CONCLUSIONS: This series of lower extremity nerve injuries in a large sample of urban lower extremity ballistic trauma noted a high rate of concomitant nerve injuries. An associated diagnosis of a vascular injury appears to portend a higher risk of neurologic injury. Treating surgeons should have a high index of suspicion for associated vascular injury in patients presenting with a ballistic lower extremity nerve palsy.


Assuntos
Traumatismos da Perna , Traumatismos dos Nervos Periféricos , Traumatismos do Sistema Nervoso , Lesões do Sistema Vascular , Ferimentos por Arma de Fogo , Humanos , Estudos Retrospectivos , Ferimentos por Arma de Fogo/complicações , Traumatismos da Perna/cirurgia , Extremidade Inferior , Paralisia
6.
Arthroscopy ; 39(3): 706-715, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36395965

RESUMO

PURPOSE: To provide a biomechanical comparison between human dermal (HD) allograft and long head of biceps tendon (LHBT) autograft with and without posterior side-to-side suturing for superior capsule reconstruction. METHODS: Eight fresh-frozen cadaveric shoulder specimens were tested in 5 conditions: (1) intact, (2) complete supraspinatus tear, (3) LHBT, (4) LHBT with side-to-side suturing, and (5) HD allograft with side-to-side suturing. Functional abduction force, superior translation of humeral head, translational range of motion, and rotational range of motion were tested at 0°, 30°, 60°, and 90° of abduction within each condition. Data were analyzed using analysis of variance with post-hoc Tukey testing for pairwise comparison, with a significance value set at .05. RESULTS: Functional abduction force in the LHBT, LHBT + suture, and HD + suture conditions was significantly increased compared with the supraspinatus tear condition at abduction angles of 30° (P = .011, .001, and .017, respectively), 60° (P = .004, .001, and .002, respectively), and 90° (P = .013, .001, and .038, respectively). In addition, superior translation of the humeral head in the LHBT, LHBT + suture, and HD + suture conditions was significantly decreased compared with the tear condition at abduction angles of 30° (P = .03, .049, .03, respectively) and 60° (P = .02, .04, .03, respectively). All 3 reconstructive techniques were statistically identical to the intact rotator cuff condition in regard to translational and rotational range of motion. CONCLUSIONS: Superior capsule reconstruction with LHBT autograft without side-to-side suturing, LHBT with posterior side-to-side suturing, and HD allograft with posterior side-to-side suturing all equivalently restore functional abduction force and decrease superior translation of the humeral head after a complete supraspinatus tear. CLINICAL RELEVANCE: Superior capsule reconstruction with long head of the biceps tendon autograft and human dermal allograft both restore functional abduction force and decrease superior translation of the humeral head, while displaying no losses in the range of motion in a cadaveric model.


Assuntos
Lesões do Manguito Rotador , Articulação do Ombro , Humanos , Lesões do Manguito Rotador/cirurgia , Autoenxertos , Articulação do Ombro/cirurgia , Ruptura/cirurgia , Aloenxertos , Cadáver , Fenômenos Biomecânicos , Amplitude de Movimento Articular
7.
J Orthop Trauma ; 37(3): e104-e110, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36219777

RESUMO

OBJECTIVES: To biomechanically investigate a novel modified all-suture construct compared with commercially available suspensory button fixation for stabilization of the syndesmosis. METHODS: Eight matched pairs of cadaver lower limbs were obtained. We used a material testing machine and Optotrak optoelectronic 3D motion measurement system for testing. Syndesmotic injuries were simulated, and specimens were fixed with either a suspensory suture button or modified all-suture construct. Repaired specimens were then cyclically loaded for 500 cycles. Spatial relationship of the tibia and fibula were continuously monitored for the intact, destabilized, and repaired states. The results were analyzed using independent samples t test. RESULTS: There was no significant difference in sagittal or coronal plane translation between intact and either repair. Compared with the intact state, both repair techniques demonstrated significantly more external rotation of the fibula relative to the tibia and decreased construct stiffness. Cycling of the specimens did not significantly increase coronal or sagittal plane translation; however, external rotation of the fibula relative to the tibia increased and stiffness decreased with cycling for both repair techniques. CONCLUSIONS: Our data suggest that sagittal and coronal plane translation is no different from the intact state for both fixation techniques. However, rotation of the fibula relative to the tibia was increased, and construct stiffness was decreased compared with the intact state for both fixation techniques. These findings suggest that an all-suture construct could offer syndesmotic fixation comparable with proprietary suspensory button fixation in a cadaver model.


Assuntos
Traumatismos do Tornozelo , Parafusos Ósseos , Humanos , Fíbula/cirurgia , Articulação do Tornozelo/cirurgia , Suturas , Traumatismos do Tornozelo/cirurgia , Técnicas de Sutura , Cadáver
8.
Polymers (Basel) ; 14(22)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36432998

RESUMO

Body-temperature programmable elastic shape memory hybrids (SMHs) have great potential for the comfortable fitting of wearable devices. Traditionally, shore hardness is commonly used in the characterization of elastic materials. In this paper, the evolution of shore hardness in body-temperature programmable elastic SMHs upon cyclic loading, and during the shape memory cycle, is systematically investigated. Upon cyclic loading, similar to the Mullins effect, significant softening appears, when the applied strain is over a certain value. On the other hand, after programming, in general, the measured hardness increases with increase in programming strain. However, for certain surfaces, the hardness decreases slightly and then increases rapidly. The underlying mechanism for this phenomenon is explained by the formation of micro-gaps between the inclusion and the matrix after programming. After heating, to melt the inclusions, all samples (both cyclically loaded and programmed) largely recover their original hardness.

9.
J Am Coll Surg ; 235(2): 285-292, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35839404

RESUMO

BACKGROUND: Infections after abdominal surgery remain a significant problem. Although preoperative antibiotic prophylaxis is a primary strategy used to reduce postoperative infections, it is typically prescribed based on standardized protocols, without attention to previous infection or antibiotic history. Patients with a previous infection after surgery may be at higher risk for infectious complications after subsequent operations owing to antibiotic resistance. We hypothesized that a previous postoperative infection is a significant risk factor for the development of infection after a second unrelated surgery. STUDY DESIGN: We performed a retrospective study of patients who had undergone 2 unrelated abdominal operations at a tertiary care center from 2012 to 2018. Clinical variables and microbiological culture results were abstracted. Univariate and multivariable regression models were constructed. RESULTS: Of 758 patients, 15.0% (n = 114) developed an infection after the first operation. After the second operation, 22.8% (n = 26) of those with a previous infection developed another infection, whereas the incidence of an infection after the second operation was only 9.5% (n = 61) in patients who did not develop an infection after the first operation. Multivariable analysis demonstrated that previous infection (odds ratio 2.49, 95% CI 1.46 to 4.25) was associated with future infection risk. Microbiological analysis found that infections after the second surgery were significantly more likely to be antibiotic resistant than infections after the first surgery (82.3% vs 64.1%; p = 0.036). Strikingly, 49% of infections after the second surgery were resistant to the antibiotic prophylaxis given at the time of incision. CONCLUSIONS: Previous postoperative infection is an independent risk factor for a subsequent postoperative infection and is associated with resistance to standard prophylaxis. Individualization of antibiotic prophylaxis in patients with a previous postoperative infection is warranted.


Assuntos
Antibioticoprofilaxia , Infecção da Ferida Cirúrgica , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle
10.
J Orthop ; 31: 121-123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35535233

RESUMO

Purpose: No validated method currently exists to preoperatively estimate tibial nail length for tibial fractures. While various anthropometric measurements have been suggested, none seem to allow for both accuracy and practicality, complicating treatment. This study aimed to evaluate the use of patient body height in preoperatively predicting tibial nail length. Methods: Patients with tibial fractures treated with intramedullary nail at a single level 1 trauma center were included. Patient body height and tibial nail size were used to develop a predictive equation. Results: 220 patients were included and reviewed in this study. A logarithmic predictive equation was developed to accurately predict tibial nail length 82% of the time. Conclusions: Tibial nail length can be accurately predicted from patient body height. Compared to other anthropometric measurements, patient body height can be easily and consistently measured. Additionally, this study involved the largest sample size compared to other anthropometric studies predicting tibial nail length.

11.
J Hand Surg Am ; 47(6): 554-560, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35216864

RESUMO

The etiology, epidemiology, and treatment outcomes of ganglions in children have not been studied in depth. Most research has mainly focused on adults with this condition, with some research suggesting differing epidemiology and outcomes in the pediatric population. This review focuses on the existing literature on pediatric ganglions of the hand and wrist, highlighting 17 studies focused on prevalence and treatment outcomes. Within the pediatric population, epidemiology and outcomes differ depending on patient age. In children aged <10 years, cysts present on the volar aspect of the wrist and are generally amenable to observation, with spontaneous regression. For patients aged >10 years, ganglions resemble those in the adult population and present on the dorsal aspect of the wrist. Open surgical excision demonstrates a relatively low recurrence rate with minimal complications and is currently recommended for treatment.


Assuntos
Cistos Glanglionares , Punho , Adulto , Criança , Cistos Glanglionares/cirurgia , Mãos/cirurgia , Humanos , Resultado do Tratamento , Punho/cirurgia , Articulação do Punho/cirurgia
12.
J Surg Oncol ; 124(7): 1106-1114, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34310702

RESUMO

BACKGROUND AND OBJECTIVES: Recent studies suggest that bacteria influence the pathogenesis of primary colorectal cancer (CRC), yet their role in recurrence after resection is largely unknown. We have discovered that collagenase-producing bacteria promote cancer recurrence in mice, and that antibiotic bowel decontamination decreases colonization of these same organisms in humans. We hypothesized that preoperative combined mechanical and oral antibiotic bowel preparation would improve disease-free survival (DFS) in patients undergoing surgery for CRC. METHODS: We reviewed a cancer registry of patients treated for CRC at a tertiary center. Patients who received bowel preparation were compared to those that did not via a 1:1-propensity score matched for follow-up, age, sex, BMI, stage, location, chemoradiation, infection, anastomotic leak, and blood transfusion. RESULTS: One thousand two hundred and seventy-nine patients met inclusion criteria. Following propensity score matching, 264 patients receiving bowel prep were matched to 264 patients who did not. Kaplan-Meier estimates showed that patients who received bowel prep had a significantly improved 5-year DFS compared to those that did not (76.3% vs. 64.2%; p < .01). Cox regression demonstrated that bowel prep was associated with improved DFS (HR, 0.57; 95% CI, 0.37-0.89; p < .01). CONCLUSION: Combined mechanical and oral antibiotic bowel preparation is independently associated with improved recurrence-free survival in patients undergoing surgery for CRC.


Assuntos
Antibioticoprofilaxia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Laxantes/administração & dosagem , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Sistema de Registros , Estudos Retrospectivos , Adulto Jovem
13.
Microcirculation ; 28(3): e12682, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33523573

RESUMO

The lymphatic system is a vast network of vessels that functions to return excess fluid from the interstitial space to the blood stream. Lymphovenous shunts are anastomoses, either natural or surgical, that connect the lymphatic and venous systems. Connections between the thoracic duct and venous system or between the right lymphatic duct and venous system are prime examples of anatomic lymphovenous shunts. Lymphovenous shunts are also present peripherally in tissues such as lymph nodes. Furthermore, pathologic lymphovenous shunts are observed in conditions such as lymphedema, malignancy, and lymphovenous malformations. Surgically, lymphovenous shunts may be constructed as an approach to treat lymphedema. Here, we discuss anatomic and surgical lymphovenous shunts in the context of normal development and disease. This perspective is intended to give an understanding of the role of lymphovenous shunts in health and disease and to show how they can be leveraged to treat disease surgically.


Assuntos
Vasos Linfáticos , Linfedema , Humanos , Linfonodos , Sistema Linfático , Vasos Linfáticos/cirurgia
14.
Cell Chem Biol ; 27(5): 525-537.e6, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32130941

RESUMO

The PI5P4Ks have been demonstrated to be important for cancer cell proliferation and other diseases. However, the therapeutic potential of targeting these kinases is understudied due to a lack of potent, specific small molecules available. Here, we present the discovery and characterization of a pan-PI5P4K inhibitor, THZ-P1-2, that covalently targets cysteines on a disordered loop in PI5P4Kα/ß/γ. THZ-P1-2 demonstrates cellular on-target engagement with limited off-targets across the kinome. AML/ALL cell lines were sensitive to THZ-P1-2, consistent with PI5P4K's reported role in leukemogenesis. THZ-P1-2 causes autophagosome clearance defects and upregulation in TFEB nuclear localization and target genes, disrupting autophagy in a covalent-dependent manner and phenocopying the effects of PI5P4K genetic deletion. Our studies demonstrate that PI5P4Ks are tractable targets, with THZ-P1-2 as a useful tool to further interrogate the therapeutic potential of PI5P4K inhibition and inform drug discovery campaigns for these lipid kinases in cancer metabolism and other autophagy-dependent disorders.


Assuntos
Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Domínio Catalítico/efeitos dos fármacos , Linhagem Celular Tumoral , Descoberta de Drogas , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular , Fosfotransferases (Aceptor do Grupo Álcool)/química , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/química
15.
J Med Chem ; 61(14): 6293-6307, 2018 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-29920098

RESUMO

Previous studies identified an adamantane dipeptide piperazine 3.47 that inhibits Ebola virus (EBOV) infection by targeting the essential receptor Niemann-Pick C1 (NPC1). The physicochemical properties of 3.47 limit its potential for testing in vivo. Optimization by improving potency, reducing hydrophobicity, and replacing labile moieties identified 3.47 derivatives with improved in vitro ADME properties that are also highly active against EBOV infection, including when tested in the presence of 50% normal human serum (NHS). In addition, 3A4 was identified as the major cytochrome P450 isoform that metabolizes these compounds, and accordingly, mouse microsome stability was significantly improved when tested in the presence of the CYP3A4 inhibitor ritonavir that is approved for clinical use as a booster of anti-HIV drugs. Oral administration of the EBOV inhibitors with ritonavir resulted in a pharmacokinetic profile that supports a b.i.d. dosing regimen for efficacy studies in mice.


Assuntos
Ebolavirus/efeitos dos fármacos , Ebolavirus/fisiologia , Internalização do Vírus/efeitos dos fármacos , Animais , Chlorocebus aethiops , Avaliação Pré-Clínica de Medicamentos , Ésteres/química , Ésteres/farmacologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células Vero
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