Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 214
Filtrar
1.
Plast Reconstr Surg ; 149(5): 914e-920e, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35271531

RESUMO

BACKGROUND: There have been no formal studies of the use of collagenase clostridium histolyticum (Xiaflex; Endo Pharmaceuticals, Malvern, Pa.) in the anticoagulated patient. Previous study on its use excluded patients receiving anticoagulation therapy. This study reviewed the effects of anticoagulation use in patients undergoing collagenase clostridium histolyticum injection and cord rupture to determine safety and efficacy. METHODS: The authors retrospectively reviewed patients receiving collagenase clostridium histolyticum injections for Dupuytren contracture between 2010 and 2017. Outcomes included type of anticoagulation, skin tear, tendon rupture, lymphadenopathy, sensory abnormality, hematoma, and bleeding. RESULTS: A total of 388 injections were performed in 197 patients. The average clinical follow-up was 311 days. Fifty-two percent of patients (n = 201) were anticoagulated. The vast majority were taking aspirin (acetylsalicylic acid) (n = 182), followed by warfarin (n = 27), clopidogrel (n = 9), apixaban (n = 8), rivaroxaban (n = 4), and dabigatran (n = 2). There were 42 skin tears, 21 in the anticoagulated group. One tendon rupture occurred in the anticoagulated group (acetylsalicylic acid) and none occurred in the nonanticoagulated group (p = 0.34). No patients experienced sensory abnormalities, a hematoma requiring intervention, or uncontrollable bleeding. CONCLUSIONS: Anticoagulation is commonly encountered by hand surgeons treating Dupuytren contracture. There is no significant difference in complications in the anticoagulated patient versus the nonanticoagulated patient. It is safe to perform collagenase clostridium histolyticum injections for Dupuytren contracture in the anticoagulated patient, regardless of the type of anticoagulation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Contratura de Dupuytren , Lacerações , Traumatismos dos Tendões , Anticoagulantes/efeitos adversos , Aspirina , Clostridium histolyticum , Contratura de Dupuytren/cirurgia , Hematoma/induzido quimicamente , Humanos , Injeções Intralesionais , Colagenase Microbiana , Estudos Retrospectivos , Resultado do Tratamento
2.
Breast Cancer ; 29(4): 599-609, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35129812

RESUMO

BACKGROUND: Breast cancer is the most common malignancy among women worldwide. As survival rates increase, breast reconstruction and quality of life gain importance. Of all women undergoing breast reconstruction, approximately, 70% opt for silicone implants and 50% of those develop capsular contracture, the most prevalent long-term complication. The collagenase of the bacterium Clostridium histolyticum (CCH) showed promising results in the therapy of capsule contracture; however, its influence on residual cancer cells is unknown. The aim of this study was to investigate whether CCH-treatment negatively impacts breast cancer cells in vitro and in vivo. METHODS: MDA-MB-231 and MCF-7 cells were used in this study. In vitro, we tested the influence of CCH on proliferation, wound healing, migration and cell cycle by MTT-assay, scratch-assay, transwell-migration-assay, and flow cytometry. In vivo, solid tumors were induced in immune-deficient mice. CCH was injected into the tumors and tumor growth and metastasis formation was monitored by caliper measurement, in vivo bioluminescence imaging and histology. Gene expression analysis was performed by microarray including 27,190 genes. RESULTS: CCH-incubation led to a dose-dependent reduction in proliferation for both cell lines, while wound healing was reduced only in MDA-MB-231 cells. No morphological alterations were monitored in cell cycle or apoptosis. In vivo, bioluminescence imaging and histology did not show any evidence of metastasis. Although CCH led to changes in gene expression of breast cancer cells, no relevant alterations in metastasis-related genes were monitored. CONCLUSION: CCH has no impact on tumor growth or metastasis formation in vitro and in vivo. This paves the way for first clinical trials.


Assuntos
Neoplasias da Mama , Contratura , Colagenase Microbiana , Animais , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Clostridium histolyticum , Colagenases/efeitos adversos , Colagenases/uso terapêutico , Contratura/tratamento farmacológico , Contratura/metabolismo , Contratura/prevenção & controle , Feminino , Camundongos , Colagenase Microbiana/efeitos adversos , Colagenase Microbiana/uso terapêutico , Qualidade de Vida , Resultado do Tratamento
3.
Int J Mol Sci ; 22(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34445258

RESUMO

Collagenases are essential enzymes capable of digesting triple-helical collagen under physiological conditions. These enzymes play a key role in diverse physiological and pathophysiological processes. Collagenases are used for diverse biotechnological applications, and it is thus of major interest to identify new enzyme variants with improved characteristics such as expression yield, stability, or activity. The engineering of new enzyme variants often relies on either rational protein design or directed enzyme evolution. The latter includes screening of a large randomized or semirational genetic library, both of which require an assay that enables the identification of improved variants. Moreover, the assay should be tailored for microplates to allow the screening of hundreds or thousands of clones. Herein, we repurposed the previously reported fluorogenic assay using 3,4-dihydroxyphenylacetic acid for the quantitation of collagen, and applied it in the detection of bacterial collagenase activity in bacterial lysates. This enabled the screening of hundreds of E. coli colonies expressing an error-prone library of collagenase G from C. histolyticum, in 96-well deep-well plates, by measuring activity directly in lysates with collagen. As a proof-of-concept, a single variant exhibiting higher activity than the starting-point enzyme was expressed, purified, and characterized biochemically and computationally. This showed the feasibility of this method to support medium-high throughput screening based on direct evaluation of collagenase activity.


Assuntos
Proteínas de Bactérias , Clostridium histolyticum/genética , Colágeno/química , Evolução Molecular Direcionada , Escherichia coli/enzimologia , Colagenase Microbiana , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Clostridium histolyticum/enzimologia , Escherichia coli/genética , Colagenase Microbiana/química , Colagenase Microbiana/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética
4.
J Hand Surg Am ; 46(10): 888-895, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34275684

RESUMO

PURPOSE: The purpose of this study was to compare reintervention and perceived recurrence, with minimum 5 years of telephone follow-up, after limited fasciectomy or collagenase Clostridium histolyticum (CCH) in the treatment of Dupuytren contracture affecting a single digit. METHODS: We performed a retrospective cohort study of 48 patients with single digit treatment who underwent limited surgical fasciectomy at one hospital and 111 patients who underwent CCH treatment at a second hospital from 2010 to 2013. Patients were contacted by telephone about reintervention and perceived recurrence. Average length of telephone follow-up was 7.3 years in the CCH group and 7.4 years in the surgery group. The 2 groups were compared using 2 methods to control for potential confounding bias: (1) propensity score matching and (2) multivariable analysis accounting for potential confounders. RESULTS: After propensity score matching, there were 44 patients in each group with similar disease and demographic characteristics. Rates of reintervention and perceived recurrence were significantly higher in the CCH group than the surgery group at a minimum of 5 years following treatment. CONCLUSIONS: Long-term overall reintervention and perceived recurrence following treatment of Dupuytren contracture affecting a single digit were higher with CCH treatment than surgical fasciectomy when comparing groups with similar baseline characteristics. Our findings may be used to counsel patients on the durability of the outcomes of treatment when considering treatment options for Dupuytren contractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Assuntos
Contratura de Dupuytren , Colagenase Microbiana , Clostridium histolyticum , Contratura de Dupuytren/tratamento farmacológico , Contratura de Dupuytren/cirurgia , Fasciotomia , Seguimentos , Humanos , Injeções Intralesionais , Colagenase Microbiana/uso terapêutico , Recidiva Local de Neoplasia , Pontuação de Propensão , Estudos Retrospectivos , Telefone , Resultado do Tratamento
5.
J Sex Med ; 18(6): 1092-1098, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34020925

RESUMO

BACKGROUND: It is currently unclear if men with Peyronie's Disease (PD) who achieve minimal benefits with the first 2 series of Collagenase Clostridium Histolyticum (CCH) injections should continue with additional injections. AIM: To analyze curvature improvements from the final two series of CCH injections based on amount of improvement during the first 2 series. METHODS: A prospective registry was analyzed of all men undergoing CCH injections for PD at a single institution. Men were included if they had completed a full 4 series (8 injections) of CCH and had baseline, interval (after 2 series), and/or final (after 4 series) curvature assessments available. Men were stratified into cohorts using baseline-to-interval assessments of ≤10° (or ≤20%) and >10° (or >20%), and improvements were compared using interval-to-final assessments. OUTCOMES: The primary outcome was interval-to-final curvature improvements stratified by ≤10°/>10° or ≤20%/>20% improvements achieved during the baseline-to-interval period. Secondary outcomes included analyses of demographic and pathophysiologic variables to determine associations with significant improvements during the final 2 CCH series. RESULTS: A total of 296 PD men were identified as receiving at least one CCH injection, of whom 175 had baseline-to-interval, 84 interval-to-final, and 115 with baseline-to-final measurements. Mean age was 56.6, PD duration 28.6 months, baseline curvature 63.4°, hourglass deformity 36.2%, and calcification 20%. Mean overall curve improvement was -21.5° (33.1%). Among men who experienced ≤20% improvements after 2 series, the mean subsequent curvature change was -24.6% during the final two series (vs +4.3% of those with >20% initial improvement, P< .001), and they were 2.7x more likely to experience >20% subsequent curve improvements. Thirty-one percent of those who achieved >10° during the first 2 series experienced benefits during the final 2 series compared to 70% of men who had ≤10° improvement initially. No demographic or pathophysiological variables predicted likelihood for improvements during the final 2 series of injections. CLINICAL IMPLICATIONS: Men who fail to achieve significant benefits with 2 series of CCH injections may benefit from completing the final 2 series. STRENGTHS AND LIMITATIONS: Strengths including a relatively large, prospective series. Limitations include a single center, nonrandomization, nonblinded assessments, and restriction to men who completed eight injections. CONCLUSIONS: In the current series, approximately 2/3 of men who fail to achieve >10° or 20% curve improvements with an initial 2 series of CCH injections achieved >10° or 20% improvements with the subsequent 2 series. Alom M, Burgon H, Ziegelmann M, et al. Continuing Collagenase Clostridium Histolyticum Injections Among Initial Nonresponders Results in Significant Curvature Improvements in the Majority of Peyronie's Disease Men. J Sex Med 2021;18:1092-1098.


Assuntos
Colagenase Microbiana , Induração Peniana , Clostridium histolyticum , Humanos , Injeções Intralesionais , Masculino , Colagenase Microbiana/uso terapêutico , Pessoa de Meia-Idade , Induração Peniana/tratamento farmacológico , Pênis , Resultado do Tratamento
8.
Sci Rep ; 11(1): 4187, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603127

RESUMO

Collagen is the most abundant protein in higher animals and as such it is a valuable source of amino acids and carbon for saprophytic bacteria. Due to its unique amino acid composition and triple-helical tertiary structure it can however only be cleaved by specialized proteases like the collagenases secreted by some bacteria. Among the best described bacterial collagenases are ColG and ColH from Clostridium histolyticum. Many Bacillus species contain homologues of clostridial collagenases, which play a role in some infections caused by B. cereus. Detailed biochemical and enzymatic characterizations of bacillial collagenases are however lacking at this time. In an effort to close this gap in knowledge we expressed ColQ1 from B. cereus strain Q1 recombinantly, investigated its metal dependency and performed peptide, gelatin and collagen degradation assays. Our results show that ColQ1 is a true collagenase, cleaving natively folded collagen six times more efficiently than ColG while at the same time being a similarly effective peptidase as ColH. In both ColQ1 and ColG the rate-limiting step in collagenolysis is the unwinding of the triple-helix. The data suggest an orchestrated multi-domain mechanism for efficient helicase activity.


Assuntos
Bacillus cereus/metabolismo , Colagenases/metabolismo , Sequência de Aminoácidos , Animais , Clostridium histolyticum/metabolismo , Colágeno/metabolismo , Cristalografia por Raios X/métodos , Suínos
9.
Diabetes ; 70(4): 917-931, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33608422

RESUMO

Efficacy of glucokinase activation on glycemic control is limited to a short-term period. One reason might be related to excess glucose signaling by glucokinase activation toward ß-cells. In this study, we investigated the effect of glucokinase haploinsufficiency on glucose tolerance as well as ß-cell function and mass using a mouse model of type 2 diabetes. Our results showed that in db/db mice with glucokinase haploinsufficiency, glucose tolerance was ameliorated by augmented insulin secretion associated with the increase in ß-cell mass when compared with db/db mice. Gene expression profiling and immunohistochemical and metabolomic analyses revealed that glucokinase haploinsufficiency in the islets of db/db mice was associated with lower expression of stress-related genes, greater expression of transcription factors involved in the maintenance and maturation of ß-cell function, less mitochondrial damage, and a superior metabolic pattern. These effects of glucokinase haploinsufficiency could preserve ß-cell mass under diabetic conditions. These findings verified our hypothesis that optimizing excess glucose signaling in ß-cells by inhibiting glucokinase could prevent ß-cell insufficiency, leading to improving glucose tolerance in diabetes status by preserving ß-cell mass. Therefore, glucokinase inactivation in ß-cells, paradoxically, could be a potential strategy for the treatment of type 2 diabetes.


Assuntos
Glucoquinase/metabolismo , Glucose/metabolismo , Metaboloma/fisiologia , Animais , Clostridium histolyticum/fisiologia , Glucoquinase/genética , Glucose/genética , Teste de Tolerância a Glucose , Imuno-Histoquímica , Células Secretoras de Insulina/metabolismo , Metaboloma/genética , Camundongos , Reação em Cadeia da Polimerase em Tempo Real
10.
ChemMedChem ; 16(8): 1257-1267, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33506625

RESUMO

Microbial infections are a significant threat to public health, and resistance is on the rise, so new antibiotics with novel modes of action are urgently needed. The extracellular zinc metalloprotease collagenase H (ColH) from Clostridium histolyticum is a virulence factor that catalyses tissue damage, leading to improved host invasion and colonisation. Besides the major role of ColH in pathogenicity, its extracellular localisation makes it a highly attractive target for the development of new antivirulence agents. Previously, we had found that a highly selective and potent thiol prodrug (with a hydrolytically cleavable thiocarbamate unit) provided efficient ColH inhibition. We now report the synthesis and biological evaluation of a range of zinc-binding group (ZBG) variants of this thiol-derived inhibitor, with the mercapto unit being replaced by other zinc ligands. Among these, an analogue with a phosphonate motif as ZBG showed promising activity against ColH, an improved selectivity profile, and significantly higher stability than the thiol reference compound, thus making it an attractive candidate for future drug development.


Assuntos
Acetanilidas/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Quelantes/farmacologia , Inibidores de Metaloproteinases de Matriz/farmacologia , Organofosfonatos/farmacologia , Acetanilidas/síntese química , Acetanilidas/toxicidade , Animais , Bacillus cereus/enzimologia , Proteínas de Bactérias/metabolismo , Linhagem Celular Tumoral , Quelantes/síntese química , Quelantes/toxicidade , Clostridium histolyticum/enzimologia , Colágeno/metabolismo , Colagenases/metabolismo , Células HEK293 , Humanos , Inibidores de Metaloproteinases de Matriz/síntese química , Inibidores de Metaloproteinases de Matriz/toxicidade , Organofosfonatos/síntese química , Organofosfonatos/toxicidade , Suínos , Peixe-Zebra , Zinco/química
11.
Sci Rep ; 11(1): 166, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420247

RESUMO

In the present study we aimed to investigate the surgical outcomes of patients with persistent penile curvature (PC) after Collagenase Clostridium histolyticum (CCH) intraplaque injections. Data from 90 patients with persistent PC after CCH in a multicentre study from 6 andrological centres were retrospectively reviewed. Three standardized surgical techniques were performed. Group 1: plaque incision grafting (PIG) with penile prosthesis implant (PPI); Group 2: PIG without PPI; Group 3: Nesbit technique. Hospital stay, operative time, postoperative complications and PC persistency/recurrence (> 20°) were evaluated. Overall satisfaction and functional outcomes were assessed through International Index of Erectile Function-Erectile Function (IIEF-EF), Peyronie's Disease Questionnaire (PDQ), Female Sexual Function Index (FSFI) administered pre and 3 months postoperatively. Of all, 25 (27.8%) patients received grafting procedure + PPI (Group 1), 18 (20.0%) patients belonged to Group 2, and 47 (52.2%) to Group 3. Bovine pericardium graft and collagen fleece have been used in in 22 (51.2%) and 21 (48.8%) patients, respectively. Median penile length after surgery was 13.0 cm (IQR 12.0-15.0). After surgery, Group 1 showed higher increase in penile length after surgery and better improvements in terms of PDQ-PS. In contrast, both IIEF-EF and FSFI scores did not differ among groups. Overall, 86 (95.6%) did not report any complication. 4 (4.4%) patients had PC recurrence; of those, 2 (8.0%), 1 (5.6%) and 1 (2.1%) cases were observed in Group 1, Group 2 and Group 3, respectively. In case of persistent PC after CCH, surgical correction by grafting with or without concomitant PPI or Nesbit technique emerged as a technically feasible, effective and safe procedure, with no significant postoperative complications.


Assuntos
Clostridium histolyticum/metabolismo , Colagenase Microbiana/farmacologia , Induração Peniana/cirurgia , Adulto , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Implante Peniano , Período Pós-Operatório , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento
12.
Aesthetic Plast Surg ; 45(3): 1273-1281, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32968820

RESUMO

BACKGROUND: Irradiation therapy limits the utilization of silicone implants for breast reconstruction due to a significant risk for capsular contracture. The injection of the collagenase of the bacterium Clostridium histolyticum (CCH) might trivialize this risk by providing a minimal-invasive treatment option by capsular contracture degradation. However, efficacy in degrading breast implant capsules induced by fractionated irradiation remains unclear. METHODS: Twenty-four rats in three groups received miniature silicone implants in a submuscular pocket. After 3D dose calculation and treatment field definition, rats of two groups underwent fractionated radiotherapy (6 × 8 Gy) using a linear accelerator. A third group served as control. On day 120, one irradiated group received injections of 0.3 mg/ml collagenase. Administration of plain solvent solution served as control in the two other groups. Outcome parameters included CT-imaging, histology, vessel wall analysis, immunohistochemistry, chemical collagen quantification and gene expression analysis. RESULTS: Fractioned irradiation leads to a significant increase in collagen deposition around silicone implants with higher capsule thickness and collagen density when comparing all groups. Additionally, significant alterations of collagen fiber deposition were evident. Vessel wall thickness was significantly increased after radiotherapy. The injection of collagenase led to a significant reduction of capsule thickness, collagen density and content. However, the collagenase application induced a significant overexpression of TGFß1. No side effects were monitored. CONCLUSIONS: The CCH proved to be a safe and effective approach to degrade capsule tissue induced by fractionated irradiation in an animal model. This may pave its way for clinical application in implant-based breast reconstruction patients. LEVEL OF EVIDENCE: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Implante Mamário , Implantes de Mama , Contratura , Animais , Implantes de Mama/efeitos adversos , Clostridium histolyticum , Colagenases , Humanos , Contratura Capsular em Implantes/etiologia , Ratos
13.
J Hand Surg Asian Pac Vol ; 25(4): 453-461, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33115367

RESUMO

Background: Management of Dupuytren Disease is variable, and influenced by multiple factors including location, extent of disease, surgical preference and familiarity with different treatment techniques. The objective of this study was to determine current Dupuytren Disease management trends in Australia. Methods: A questionnaire was sent through The Australian Hand Surgery Society to all members. In addition to demographic data, indications and preferences for different management interventions were surveyed on location of disease, age and activity level of the patient. Results: 99 (48%) of the Australian Hand Surgery Society members completed the survey. Respondents were primarily Orthopaedic (50%) or Plastic (49%) Surgeons, and most worked in private (99%) and public (71%) practice. Surgeon's believed that Tubiana's treatment goals to correct deformity was the most important (60%) and to shorten post-operative recovery (60%) was the least important. Only 42% of respondents perform needle aponeurotomy for Dupuytren Disease. In contrast 70% of respondents perform collagenase injections, with manipulation most commonly undertaken on the second day (46%) and skin tears (52%) the most common complication. Seventy-five percent of the respondents feel there is sufficient evidence to support the treatment of Dupuytren disease with collagenase injections. Ninety nine percent of all respondents perform fasciectomes for Dupuytren Disease, with Limited (without graft) (76%) the most routine performed. Conclusions: Several procedural options for the treatment of Dupuytren Disease exist within Australia. This study shows current Australian practice trends and highlights the increasing use of collagenase.


Assuntos
Contratura de Dupuytren/terapia , Padrões de Prática Médica/estatística & dados numéricos , Cirurgiões , Adulto , Idoso , Austrália , Clostridium histolyticum , Fasciotomia/estatística & dados numéricos , Humanos , Injeções/estatística & dados numéricos , Colagenase Microbiana/uso terapêutico , Pessoa de Meia-Idade , Agulhas , Inquéritos e Questionários
14.
Drug Des Devel Ther ; 14: 2707-2713, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764872

RESUMO

BACKGROUND/HYPOTHESIS: Adhesive capsulitis of the shoulder results in pain and restricted movement of the glenohumeral joint. Hypothesis: There would be a difference in active range of movement in the affected shoulder of patients with adhesive capsulitis after receiving a series of injections of collagenase Clostridium histolyticum (CCH) compared to placebo. METHODS: This study reports the results from a single site that was part of a 321-participant, multicenter, double-blind, prospective parallel-group, randomized controlled clinical trial. Inclusion criteria: over 18 years of age, unilateral idiopathic adhesive capsulitis for >3 months, but <12 months. Exclusion criteria: recent physical therapy, injections, subacromial impingement, calcific tendonitis or glenohumeral joint arthritis in the affected shoulder. Subjects were randomized 3:1 to receive CCH 0.58 mg or placebo under ultrasound guidance. Injections were on days 1, 22, and 43. The primary outcome measure was a functional assessment of active range of movement. RESULTS: Overall, 37 patients were screened, 26 subjects were excluded, and 11 subjects were randomly assigned to the treatment group (n=9) or the control group (n=2). Both control and treatment groups showed improvement in ROM between baseline and day 95. In the treatment group, AROM improved from the baseline of 272.89° (SD 86.25) to 462.11° (SD 96.89) and the control group from 246.00° (SD 5.66) to 451.50° (SD 50.20) at day 95 with no statistical difference between groups p=0.78. Site data were in line with the whole study findings. Treatment-related adverse events at the injection site, including haematoma (bruising) and localised pain and swelling, were common. CONCLUSION: Although the participants showed improvement in function, statistical significance was neither reached in the site nor the overall study cohort. Given the adverse events and the potential risks of the procedure, we would not recommend this drug for the treatment of adhesive capsulitis of the shoulder. LEVEL OF EVIDENCE: 2, cohort from one site of RCT.


Assuntos
Bursite/terapia , Clostridium histolyticum/enzimologia , Colagenases/efeitos adversos , Adulto , Bursite/diagnóstico , Bursite/fisiopatologia , Colagenases/administração & dosagem , Colagenases/metabolismo , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ombro/fisiopatologia
15.
Andrologia ; 52(10): e13740, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32780475

RESUMO

The intraplaque injection of collagenase from Clostridium Histolyticum (CCH) was established as an effective therapeutic alternative for selected patients with Peyronie's disease (PD). There is no consensus on the use of pre-procedure anaesthesia. The aim of this pilot study was to assess the efficacy and safety of dorsal penile block before CCH injections in reducing procedure related pain. The treatment protocol described in the IMPRESS trials was adopted. The first injection of the first cycle was given without anaesthesia, while the second after penile block. After the administration of each injection, the pain related to the procedure was evaluated with the Wong-Baker-FACES® -Pain-Rating-Scale. Thirty patients were included. Mean age 56.7 (SD: 9.61) years. Mean basal penile curvature 59.37º (SD: 18.26). The mean pain value related to the procedure measured after the first injection of the first cycle (without anaesthesia) was 5.4 (SD: 2.13), while after the second injection (with anaesthesia) was 2.5 (SD: 1.92), (p < .001). The treatment was more painful in patients with dorsal plaques (mean:6.2) than in patients with lateral plaques (mean: 4.35) (p = .01). We can conclude that penile block before CCH injection in patients with PD seems an effective and safe measure to decrease the pain related to the procedure.


Assuntos
Induração Peniana , Nervo Pudendo , Clostridium histolyticum , Colagenases/uso terapêutico , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Induração Peniana/tratamento farmacológico , Pênis , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
16.
J Hand Surg Am ; 45(10): 989.e1-989.e10, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32546304

RESUMO

PURPOSE: Skin tears are an unpleasant complication that may occur after collagenase Clostridium histolyticum (CCH) administration to treat Dupuytren contractures of the fingers. The purpose of this study was to determine risk factors for the development of this complication. METHODS: Over a 6-year period, patients with a measurable metacarpophalangeal or proximal interphalangeal joint Dupuytren contracture and a palpable cord treated with CCH were prospectively observed. Patients were assessed for the development of skin tears immediately on the day of manipulation as well 30 days or more after manipulation. RESULTS: A total of 117 patients (174 cords) met inclusion criteria. There was a 25.6% incidence of skin tears (30 of 117 patients; 33 skin tears). Multivariable regression analysis revealed that patients with a combined digital flexion contracture (total combined metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joint contracture) of 75° and greater and those treated with 2 simultaneous doses of CCH in the same hand were more likely to sustain a tear. All skin tears healed with nonsurgical management at short-term follow-up. CONCLUSIONS: Although a relatively minor complication, skin tears are not well-tolerated by all patients and may change the postinjection course of orthosis use, wound care, and manual activity. Based on these results, patients with digital contractures 75° or greater and those treated with 2 simultaneous doses of CCH in the same hand may be counseled that they have a higher likelihood of developing a skin tear during manipulation. Pretreatment education may reduce anxiety experienced by patients who otherwise unexpectedly develop a skin tear at the time of manipulation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.


Assuntos
Contratura de Dupuytren , Colagenase Microbiana , Pele/lesões , Clostridium histolyticum , Contratura de Dupuytren/tratamento farmacológico , Humanos , Injeções Intralesionais , Colagenase Microbiana/efeitos adversos , Fatores de Risco , Resultado do Tratamento
17.
Biomolecules ; 10(6)2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521614

RESUMO

The metabolic variation in the essential oil composition of Premna odorata leaves obtained from different seasons was quantitatively and qualitatively determined employing GC/MS (Gas Chromatography coupled with Mass Spectrometry) and GC/FID (Gas chromatography equipped with flame ionization detector) techniques. It displayed the existence of 97 constituents accounting for 94.19%, 92.27%, 91.95% and 92.63% for POS (spring), POM (summer), POA (autumn) and POW (winter) whole essential oils. ß-Caryophyllene constituting the main metabolite in the oil in the different seasons. To better visualize the differences between them, GC data were exposed to chemometric analysis. A PCA (principal component analysis) score plot revealed the closeness of POS and POW. Molecular modelling on collagenase, elastase and hyaluronidase enzymes active centres shows that different compounds existing in the essential oil of Premna odorata leaves shows binding to the active sites with variable degrees that suggested its anti-ageing potential. Palmitic acid displayed the highest fitting for both the collagenase and elastase active centres in both pH-based and rule-based ionization methods with ∆G equals -78.27 and -44.77 kcal/mol, respectively; meanwhile, heptacosane showed the highest fitting score in the hyaluronidase centre with ∆G = -43.78 kcal/mol. In vitro assays consolidates the obtained modelling studies in which essential oil shows considerable anti-elastase and anti-hyaluronidase potential as evidenced by their IC50 values being 49.3 and 37.7 µg/mL, respectively; meanwhile, the essential oil of Premna odorata leaves displayed mild anti-collagenase potential. Thus, it can be concluded that Premna odorata could serve as a promising anti-ageing naturally occurring drug that could be effectively incorporated by pharmaceutical industries in cosmetics combating ageing and skin wrinkling.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Óleos Voláteis/farmacologia , Estações do Ano , Verbenaceae/química , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Bovinos , Clostridium histolyticum/enzimologia , Colagenases/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Hialuronoglucosaminidase/antagonistas & inibidores , Hialuronoglucosaminidase/metabolismo , Modelos Moleculares , Óleos Voláteis/química , Óleos Voláteis/metabolismo , Elastase Pancreática/antagonistas & inibidores , Elastase Pancreática/metabolismo , Folhas de Planta/química , Análise de Componente Principal
18.
J Med Chem ; 63(15): 8359-8368, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32470298

RESUMO

In light of the global antimicrobial-resistance crisis, there is an urgent need for novel bacterial targets and antibiotics with novel modes of action. It has been shown that Pseudomonas aeruginosa elastase (LasB) and Clostridium histolyticum (Hathewaya histolytica) collagenase (ColH) play a significant role in the infection process and thereby represent promising antivirulence targets. Here, we report novel N-aryl-3-mercaptosuccinimide inhibitors that target both LasB and ColH, displaying potent activities in vitro and high selectivity for the bacterial over human metalloproteases. Additionally, the inhibitors demonstrate no signs of cytotoxicity against selected human cell lines and in a zebrafish embryo toxicity model. Furthermore, the most active ColH inhibitor shows a significant reduction of collagen degradation in an ex vivo pig-skin model.


Assuntos
Proteínas de Bactérias/metabolismo , Clostridium histolyticum/enzimologia , Colagenases/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Metaloendopeptidases/metabolismo , Pseudomonas aeruginosa/enzimologia , Succinimidas/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Linhagem Celular , Infecções por Clostridium/tratamento farmacológico , Clostridium histolyticum/efeitos dos fármacos , Humanos , Inibidores de Metaloproteinases de Matriz/química , Metaloendopeptidases/antagonistas & inibidores , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Succinimidas/química , Suínos , Peixe-Zebra
19.
Expert Opin Biol Ther ; 20(6): 559-564, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32345061

RESUMO

Introduction: Collagenase clostridium histolyticum (CCH) is the first and only licensed medical treatment for men with Peyronie's disease (PD). Published literature shows intralesional CCH injection as an effective and safe minimally invasive treatment in a specific subgroup of PD patients.Areas covered: The authors discuss pharmacodynamics and pharmacokinetics as well as clinical outcomes and safety profile from major CCH studies in PD. All relevant CCH studies published in PubMed and EMBASE databases up to June 2019 were included.Expert opinion: Given the variability in treatment schedule and drug access coupled with the potential need for further treatment, strict patient selection and the use of adjunctive strategies are key determinants to maximize clinical efficacy of intralesional CCH. Furthermore, longer-term follow-up data on the clinical outcomes, safety and durability of CCH in larger multi-center studies and post-marketing surveillance data are necessary to provide a comparison to other standard PD treatment options.


Assuntos
Clostridium histolyticum/enzimologia , Colagenase Microbiana/uso terapêutico , Induração Peniana/terapia , Esquema de Medicação , Equimose/etiologia , Humanos , Injeções Intralesionais , Masculino , Colagenase Microbiana/metabolismo , Ereção Peniana/fisiologia , Resultado do Tratamento
20.
Clin Drug Investig ; 40(6): 583-588, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32342279

RESUMO

BACKGROUND AND OBJECTIVE: Plaque formation ordinarily takes place in the acute phase of Peyronie's disease. There is no unanimous consent regarding the management of the acute phase of Peyronie's disease. The objective of this study was to evaluate the advantages of using a single intralesional injection of collagenase Clostridium histolyticum in patients with the active phase of Peyronie's disease and to assess its effect on disease progression by reducing penile curvature and ameliorating pain during sexual intercourse. METHODS: Sexually active men aged older than 18 years with the acute phase of Peyronie's disease were enrolled. All patients received treatment with a single intralesional injection of collagenase Clostridium histolyticum. The primary outcome of the study was the change in penile curvature after treatment while secondary outcomes were the change in sexual function (International Index of Erectile Function [IIEF-5]) and in the Peyronie Disease Questionnaire (PDQ) and its sub-scores, PDQ-PS (psychological symptoms), PDQ-PP (penile pain) and PDQ-BD (bother disease). RESULTS: Overall, 74 patients were enrolled. Mean penile curvature at baseline was 41.1° ± 12.2°. The mean changes before and at the 3-month evaluation in terms of penile curvature, Visual Analog Scale score at rest, and Visual Analog Scale score during intercourse were - 19.3 ± 8.4 (p < 0.0001), - 0.8 ± 1.1 (p < 0.0001) and - 3.8 ± 0.9 (p < 0.0001) with the benefit persisting also after 6 months. Moreover, improvements of mean IIEF-5 score (1.1 ± 0.9, p = 0.03; 0.9 ± 0.5, p = 0.02), PDQ-PS (- 2.7 ± 2.2; - 2.5 ± 2.0, p = 0.01), PDQ-PP (- 1.2 ± 1.6; - 1.1 ± 1.2, p = 0.02) and PDQ-BD (- 3.8 ± 3.4; - 3.5 ± 3.1, p = 0.001) were observed 3 and 6 months after the end of treatment, respectively. At the multivariable regression analysis, the time since disease onset (modelled with non-linear terms) and baseline curvature were independently associated with the degree of curvature improvement (coefficient: 0.30; 95% confidence interval 0.16-0.44) after a single intralesional injection (all p < 0.03). CONCLUSIONS: Although intralesional therapy with collagenase Clostridium histolyticum is not yet indicated for the acute phase of Peyronie's disease, these preliminary results suggest the effectiveness of this minimally invasive option by improving penile curvature and IIEF-5 and PDQ scores.


Assuntos
Clostridium histolyticum/enzimologia , Colagenases/uso terapêutico , Induração Peniana/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Idoso , Colagenases/administração & dosagem , Progressão da Doença , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Dor , Inquéritos e Questionários , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...