How Atypical Penile Curvature Influence Clinical Outcomes in Patients with Peyronie's Disease Receiving Collagenase Clostridium Histolyticum Therapy?

Collagenase Clostridium Histolyticum Injection for Dupuytren Contracture: 2-Year Follow-up

BACKGROUND: Dupuytren disease is characterized by the development of palmar fibrous tissue that can lead to fixed flexion contracture (FFC) and contribute to functional loss of the involved digits. Our goal was to investigate rates of contracture resolution and recurrence in patients who underwent enzymatic fasciotomy for Dupuytren contracture consisting of collagenase clostridium histolyticum (CCH) injection followed by passive manipulation combined with splinting and home-based therapy. METHODS: We prospectively enrolled 34 patients (44 metacarpophalangeal [MCP] and 33 proximal interphalangeal [PIP] joints) treated by one orthopaedic hand surgeon between November 2010 and November 2014. On day 1, CCH was injected into a palpable fibrous cord of the involved fingers. The next day, the finger was passively extended to its maximal corrective position. FFC was measured for each joint before injection and immediately after manipulation. Patients were instructed to wear an extension splint at night and perform stretching exercises at home and were re-evaluated at 6 weeks, 4 months, 1 year, and 2 years. Resolution was defined as improvement of contracture to ≤ 5° of neutral. Recurrence was defined as an increase in FCC of ≥ 20° after treatment. RESULTS: Immediate contracture resolution occurred in 42 of 44 MCP joints (p < 0.001), improving from 50° to 1.5°, and in 14 of 33 PIP joints (p = 0.182), improving from 44° to 16°. Four joints had recurrence within 6 weeks. Of the 48 joints with minimum 4-month follow-up (mean, 26 months), 12 had recurrence at 2-year follow-up (MCP, 6; PIP, 6). At 2-year follow-up, MCP and PIP contractures measured 17° and 35.5°, respectively. Older age and multiple digit involvement were associated with higher recurrence rates. CONCLUSIONS: CCH offers a safe, nonoperative option to correct FCC in Dupuytren disease with greater success for MCP joints compared to PIP joints. There is a tendency of reoccurrence within 2 years of treatment. Further investigation is needed to determine optimal timing of repeat CCH injection to improve upon or extend the period of contracture resolution.

The Impact of Clostridium Histolyticum Collagenase on the Prevalence and Management of Peyronie's Disease in the United States

PURPOSE: We evaluated the impact of collagenase clostridium histolyticum (CCH) on rates of diagnosis, treatment, and corporal rupture in Peyronie's disease (PD). We examined the impact of CCH on cost of PD treatment. MATERIALS AND METHODS: We extracted data on PD diagnosis (ICD-9 607.95 and ICD-10 N48.6), corporal rupture (ICD-9 959.13 and ICD-10 S39.840A), CCH use (J0775), penile injections (CPT 54200), and corporal rupture repair from 2008 to 2016 in men over 40 years old using the Clinformatics® Data Mart Database (3.7 to 4.9 million males). We analyzed for prevalence of PD, rates of PD treatments, cost associated with treatment, and rates of corporal rupture and repair by year. RESULTS: The prevalence of PD was 0.29% in 2013 and did not increase after CCH entered the market in 2014. An average of 2.52% of men with PD received treatment before CCH, compared with 3.75% after (p<0.0001). Penile injection rates increased (1.34% vs. 2.61%, p<0.0001), while rates of surgical treatments decreased between these periods. There was no change in rate of corporal rupture in men with PD before (0.024%) and after (0.024%) CCH. Overall, only 20.0% of corporal ruptures were repaired. After CCH entered practice, a significant increase in cost occurred (p=0.013). CONCLUSIONS: The prevalence of men with PD did not change after CCH. However, more men with PD received treatment due to an increase in penile injections. The cost of treating PD increased after CCH became available. The overall prevalence of corporal rupture did not change after CCH entered the market.

Collagenase clostridium histolyticum for Peyronie's disease: A new minimally invasive and effective treatment / 中华男科学杂志

The treatment of Peyronie's disease has been a challenge to urologists, as most of the current oral medications are considered hardly valid and the rest of the therapies require strict control of indications, some of which remain controversial, while the final surgical option may be associated with complications such as penile shortening or erectile dysfunction. Collagenase clostridium histolyticum has been proved to be effective in dissolving the penile cavernosal plaque and approved by the Food and Drug Administration of the USA as the first drug to be used for the treatment of Peyronie's disease. This article presents an introduction to the characteristics, safety, efficacy, and procedures of this new treatment, which may benefit urologists and the patients with Peyronie's disease.

Collagenase Clostridium Histolyticum in the Treatment of Peyronie's Disease: Review of a Minimally Invasive Treatment Option

Peyronie's disease (PD) is an inflammatory disorder characterized by an abnormal collagen deposition in the tunica albuginea of the penis, leading to fibrous and non-compliant plaques that can impede normal erection. Although pharmacological treatments are available, only intralesional injection therapy and surgical reconstruction have demonstrated tangible clinical efficacy in the management of this condition. Intralesional injection of collagenase clostridium histolyticum (CCH) has come to the forefront of minimally invasive treatment of PD. In this review, the authors provide an update on the safety, efficacy, and indications for CCH. The efficacy of CCH will be assessed on the basis of improvement in the severity of penile fibrosis, curvature, and pain. Numerous well-designed clinical trials and post-approval studies involving more than 1,500 patients have consistently demonstrated the efficacy and tolerability of CCH in the treatment of PD. CCH significantly decreases penile curvature and plaque consistency, as well as improves quality of life. Post-approval studies continue to demonstrate the efficacy of CCH despite broader inclusion criteria for treatment, such as the case with acute phase disease and atypical plaque deformities (i.e., ventral plaques, hourglass narrowing). CCH continues to be the gold standard for non-surgical management of stable phase PD, in the absence of strong evidence supporting oral therapy agents and ongoing evaluation of extracorporeal shockwave therapy. However, recent studies are beginning to provide precedent for the use of CCH in the management of acute phase and atypical PD.

Effect of dopamine on the activity of matrix metalloproteinases and degradation of dentin collagen / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the inhibition effect of dopamine on the activity of matrix metalloproteinases (MMP) and the effect of dopamine on degradation of dentin collagen for its potential use in caries treatment and dentin adhesive.</p><p><b>METHODS</b>In the experiment of MMP activity test, 2.0 g/L dopamine + 1.0 g/L highly purified collagenase type VIII from Clostridium histolyticum served as the experimental group, and deionized water + 1.0 g/L highly purified collagenase type VIII from Clostridium histolyticum served as the negative control group, and 2% chlorhexidine + 1.0 g/L highly purified collagenase type VIII from Clostridium histolyticum served as the positive control group, and the mixture volume ratio of the two ingredients in every group was 1:9. After 15 minutes, the enzyme activity of each sample was tested by MMP activity colerimetric quantitative detection kits, and the test was repeated 5 times in each group. In the experiment of collagen degradation, the dentin slices were demineralized with 37% phosphoric acid for 1 min. In sequence, 2 dentin slices were used to observe the morphology, and the remaining 30 dentine slices were randomly divided into three groups (n = 10) according to random number table: the negative control ones were stored in 100 µl deionized water and 900 µl collagenase (7 days, 37 °C), the positive control ones were stored in 100 µl chlorhexidine and 900 µl collagenase (7 days, 37 °C) and the experimental specimens were stored in 100 µl dopamine and 900 µl collagenase (7 days, 37 °C). The degraded collagen was investigated by assaying hydroxyproline. The framework of collagen was evaluated with field emission scanning electron microscope (FE-SEM).</p><p><b>RESULTS</b>The statistical results of completely random design ANOVA showed that the MMP activity and the amount of degraded collagen of the negative control group [(0.089 ± 0.011) µmol · min⁻¹ · mg⁻¹ and (2 837 ± 201) µg/cm²] were significantly higher than those of the positive control group [(0.038 ± 0.006) µmol · min⁻¹ · mg⁻¹ and (1 288 ± 172) µg/cm²] and the experimental group [(0.030 ± 0.009) µmol · min⁻¹ · mg⁻¹ and (1 389 ± 255) µg/cm²] (P < 0.05). SEM observation indicated that the structural integrity of the collagen network on dentin still existed in experiment samples and positive control groups, however, collagen fibrils were destructed and the structural integrity disappeared in the negative control groups.</p><p><b>CONCLUSIONS</b>Dopamine may inhibit MMP activity and reduce the amount of degraded collagen.</p>

Collagenase activity in prevotella bivius Isolated from patients with premature rupture of membranes

Bacterial vaginosis [BV] has been considered to be the most prevalent infection found in sexually active women. BV is thought to paly an important role in the premature rupture of membranes [PROM] and preterm birth. Preterm delivery accounts for a substantial percentage of low birth weight infants and perinatal mortality and morbidity. Bacteroides and Prevotella species have been isolated from the amniochorion of women with preterm birth and PROM. Women with >10 [4]/mL Prevotella bivius [formerly Bacteroides bivius] have a 60-100% higher rate of preterm delivery. The purpose of this study was to determine wether some strains of Prevotella species isolated from PROM and BV patients produce proteases especially collagenase enzymess which faciliate the rupture of membranes leading to preterm birth. Vaginal specimens have been obtained from 120 women with BV and premature rupture of membrane in 30-44 weeksss gestational age. Twenty anaerobic coccobacilli consisiting of Bacteroides fragilis, black pigmented Bacteroides and Prevotella bivius were isolated and identiofied. The isolates were examined for protease activity, using porcine skin gelatin and casein as substrates by Martleys method. Elastase and collagenase activity were detected using elastin, guinea pig collagen, bovine Achilles tendon collagen, FALGPA and GP, VPR as substrates by leverson method. Collagenase and elatase activity was detected in 90 and 100% of isolates. Gelatinase and caseinase activity was detected in 40 and 50% of isolates. Collagenase produced by Prevotella bivia isolates was purrified by ammonium sulphate precipitation, gel filtration and ion exchange chromatography. The collagenase was cleaved from the synthetic collagen substrate FALGPA, and GP, VPK substrates. The activity of the enzyme was inhibited by EDTA, Antipain and PMSF. This study suggests that proteases produced by Prevotella bivia may be involved in pathogenesis of premature rupture of membrane. PROM before 37 weeks has been reported to be significantly higher among patients with Bacteroides and Prevotella colonisation of the genital tract. The amniochorion consists of collage and elastin which convey physical integrity to the placenta. Collagenase and elastase released into genital tract may promote connective tissue destruction in the cervix and chorioammion membranes

Colagenase óvulos na pós-cauterizaçäo do colo uterino / Collagenase ovules in post-cauterization of uterine cervix

O autor estudou a colagenase sob a forma de óvulos vaginais na pós-cauterizaçäo do colo uterino. O estudo foi duplo-cego e constou de 40 pacientes, sendo que 20 receberam placebo e 20 a substância ativa. Os óvulos eram fornecidos às pacientes aleatóriamente. Foi observada uma melhora acentuada na cicatrizaçäo do colo uterino das pacientes que usaram a substância ativa. A tolerabilidade do medicamento, a evoluçäo da cicatrizaçäo e a eficácia do medicamento foram muito boas. A citologia e a bacterioscopia foram melhores na fase final. Näo houve efeitos colaterais. Aconselha o autor o uso de Colagenase com Clorafenicol óvulos no tratamento do colo uterino após a cauterizaçäo

Ruptura prematura de membranas: mecanismos de la enfermedad / Premature rupture of the choriommiotic membranes: physiopathogenic mechanism

La ruptura de membranas corioamnióticas (RPM) está asociada a complicaciones perinatales y es la causa identificada más frecuente de parto pretérmino. A pesar de que la RPM se ha estudiado desde hace tiempo, en las actualidad hay controversia entre los mecanismos que la median y su etiopatogenia no ha sido bien comprendida. Actualmente se reconoce que el rompimiento de las membranas se asocia al aumento de presión intrauterina, siendo una diferencia que las membranas que se rompen en forma prematura son más débiles que las normales, sin embargo, la pura explicación mecánica parece incompleta, por lo que se han estudiado otros factores que podrían estar relacionados con la RPM entre los que se encuentran el infeccioso, el dietético y otros como pueden ser maniobras quirúrgicas, incompetencia ítsmico-cervical y polihidramnios. Por otro lado se han analizado aspectos moleculares relacionados con la RPM, estas comprenden studios sobre el metabolismo de la colégena que es principal constituyente de las membranas corioamnióticas, como resultado de ellos, se han propuesto diferentes niveles de daño que adectan tanto a la síntesis como a la degradación de la colágena

Cuantificación de colagenasa en pulpas de dientes temporales y permanentes / Quantification of collagenase in pulps from primary and permanent teeth

Con el fin de determinar y comparar la cantidad de colagenasa en pulpas de dientes temporales y permanentes, asociándola al proceso fisiológico de la reabsorción radicular en dientes temporales, se realizó este estudio en 25 pulpas sanas de 14 dientes permanentes y 11 temporales. Se cuantificó la cantidad de colagenasa empleando anticuerpos policlonales y detectándola por medio de la técnica de ELISA. Se estimó un promedio de colagenasa para las pulpas de dientes temporales de 49.02 ng. y para las pulpas de dientes permanentes de 35.72 ng. Estos hallazgos permiten evidenciar una diferencia significativa entre los dos tipos de pulpas, sin embargo es probable que el mecanismo de regulación enzimática no esté relacionado únicamente con la cantidad de la enzima, sino con su "actividad o inactividad" y por tanto la función de la colagenasa en la pulpa no sea igual en ambos tipos de dentición

A monoclonal antibody specific for a 40 kDa polypeptide recognizes pathogenic strains of Entamoeba histolytica

In vitro interaction of Entamoeba hystolytica trophozoites with collagen induces the intracellular formation and release of electron-dense granules (EDGs). We determined that four polypeptides in EDGs total antigen by SDS-PAGE were absent in trophozoite extracts. A monoclonal antibody raised against these EDGs recognized a polypeptide of 40 kDa specific for the pathogenic strains of E. histolytica. In addition, this mAb recognized a 96 kDa peptide masked by carbohydrates

La matriz extracelular y los diferentes tipos de colágena / The extracellular matrix and the different collagen types

Las cilágenas son una familia de proteínas que forman parte de la matriz extracelular. Se han descrito hasta ahora, 14 tipos genéticos que tienen en común, ser proteínas estructurales que contienen uno o más dominios con una estructura de triple hélice. Todas las moléculas participan en agregados supramoleculares y forman estructuras muy variadas que se han intentado agrupar en diferentes clases. 1) las colágenas fibrilares que se encuentran en la mayoría de los tejidos conjuntivos y que constituyen las fibras con bandas características que se observan al microscopio electrónico (colágenas tipo I, II, III V y XI); 2) Las colágenas, con triple hélice interrumpida, asociadas a fibras que parecen conectar las fibrillas a otros elementos de la matriz (colágenas tipo IX, XII y XIV); 3) Las colágenas que forman láminas basales o membranas proteicas que rodean tejidos u organismos (colágenas tipo IV y VIII); 4) Colágenas que forman fibrillas de encaje entre el epitelio basal y las fibras de colágenas (colágena tipo VII); 5) Colágenas que forman filamentos en rosario que pueden interactuar entre las fibras y las células (colágenas tipo VI)

Fine structure of sensore nerve endings and SEM study of the palatine mucosa of rats

Se estudió la estructura fina de las terminaciones sensoriales nerviosas, a través de microscopÍa electrónica de barrido de la superficie celular y del tejido conectivo epitelial. La superficie epitelial de la mucosa palatina de la rata mostró una superficie de células planas y algunas elevaciones de la mucosa. La superficie de la célula está caracterizada por la presencia de numerosos micropliegues. Especímenes tratados con HCL-colagenasa revelaron que la interfase del tejido conectivo-epitelial presentaba varios surcos, circulares y alargados. Las pequeñas proyecciones citoplasmáticas son claramente visibles. Las terminaciones nerviosas libres bajo el epitelio se encuentran en el pequeño tejido conectivo papilar y están circundados por una delgada lámina de células de Schwann. El axoplasma mostró numerosas mitocondrias, neurofilamentos cuerpos multicorpustulares y pequeñas protusiones citoplasmáticas

Rabbit parotid gland acini as revealed by scanning electron microscopy

Foi utilizada a técnica de HCL-colagenase pra observar a superfície dos ácinos de glândula parótida de coelhos. Evidenciaram-se numerosos grupamentos de ácino, contendo cada um vários ácinos de forma esféricas que meem de 10 a 25 micronm de diâmetro. Cada ácino possui uma superfície lisa e ligeirametne convexa. Também existem pequenos vasos nos espaços interacinares medindo de 3 a 5 micronm de diâmetro. As fibras nervosas terminais associadas säo notadas ao longo da superfície dos ácinos. Näo foram observadas células mioepiteliais junto a superfície dos ácinos

Preparación de células paratiroides caninas vivas mediante digestión enzimática: descripción del método / Canine parathyroid cells preparation employing enzyme digestion: description of the method

La secreción de hormona paratiroidea (PTH) se ha caracterizado con una preparación de células individuales, obtenidas mediante digestión enzimática de glándulas paratiroides previamente fragmentadas, obtenidas quirúrgicamente d diferentes especies, incluida la humana. Esta preparación permite establecer condiciones experimentales controladas, imposibles de obtener en vivo. Tiene además la ventaja de conservar todas las funciones secretoras de las células intactas, inclusive, las de los tejidos anormales. Este trabajo describe las modificaciones metodológicas necesarias para obtener una preparación de células paratiroideas a partir de glándulas caninas, especie en la que el metabolismo mineral es muy similar al del humano y que se puede estudiar experimentalmente con facilidad. Demonstramos que, en estas células, tanto el curso temporal como la influencia de las concentraciones extracelulares de calcio influyen de manera normal en la secreción de PTH, misma que aumentó sobre la secreción basal hasta 264.4 ñ 53.9 pg/10 células cuando la concentración extracelular de calcio fue de 0.5 mM y hasta 212 ñ 51.1 pg/10 células a concentración extracelular de calcio de 2.0 mM (p < 0.05). La región linear del incremento temporal en secreción de PTH mostró una correlación altamente significativa en ambas concentraciones de calcio (0.5 mM r = 0.93, 2mM r = 0.97). Concluimos que utilizando este método se obtiene células paratiroideas individuales, viables, que conservan su capacidad secretora intacta, aplicables al estudio del funcionamiento paratiroideo canino in vitro

Isolamento das ilhotas de Langerhans pela digestäo do tecido pancreático com colagenase tipo V: estudo experimental em cäes / Isolation of islets of Langerhans by digestion of pancreatic tissue with collagenase type V: experimental study in dogs

O autotransplante de ilhotas de Langerhans é método usado na prevençäo, correçäo ou minimizaçäo do diabetes pancreático. Um dos pontos críticos para o êxito desse empreendimento é o método de separaçäo e enriquecimento do tecido insular pancreático. Para estudar a açäo da colagenase, 23 pâncreas de cäes obtidos por pancreatectomia total, depois de devidamente manipulados, foram incubados com colagenase na dosagem de 600 unidades/grama de tecido pancreático. Constituiu-se também um grupo controle composto por 15 cäes, nos quais foi utilizada a mesma metodologia, mas näo se empregou a enzima. Os resultados mostraram que o conteúdo tecidual de insulina foi maior e o conteúdo tecidual de amilase foi menor nos tecidos pancreáticos tratados com colagenase. A contagem dos elementos histológicos mostrou que o tecido pancreático tratado com colagenase teve um conteúdo menor de tecido colágeno (< ou = 0,0001), e maior de tecido endócrino (p< ou - 0,0001). Concluiu-se que a preparaçäo de tecido pancreático com colagenese aumentou a concentraçäo de tecido endócrino, fazendo com que as ilhotas ficassem mais isoladas do restante do parênquima pancreático. Além disso, a diminuiçäo do conteúdo tecidual de amilase, e, por analogia, dos demais fermentos pancreáticos exócrinos, reduziria a açäo lesiva da secreçäo exócrina pancreática sobre as ilhotas. Esses resultados sugerem uma açäo eficaz da colagenase tipo V no isolamento e na concentraçäo das ilhotas pancreáticas

Cicatrizaçäo de lesöes cutâneas com o uso de colagenase associada a cloranfenical em pomada / Cutaneous wounds cicatrization with the use of colagenases associated with chloranfenicol in ointment form

Foram estudados 20 indivíduos com lesöes cutâneas, sendo oito com lesöes actínicas, quatro com dermatite química por fármacos antineoplásicos, dois com úlcera varicosa e seis com lesöes metastáticas ulceradas e infectadas. Usou-se, localmente, associaçäo de clostridiopeptidase A + proteases e cloranfenicol, precedido de limpeza com líquido de Dakin e água oxigenada, duas vezes ao dia. O critério usado para a obtençäo dos resultados foi o seguinte: + (cura de lesäo inicial); ++ (melhora em cerca de 50% da lesäo inicial); +++ (inalteraçäo da lesäo) e ++++ (progressäo da lesäo). Os resultados obtidos foram os seguintes: a. oito actínicas: + para cada; b. quatro dermatites químicas: uma com + e três com + + +; c. duas úlceras varicosas: + para cada uma; d. seis lesöes metastáticas: quatro com + + + + e duas com + + + (com melhora da infecçäo subjacente em todos)