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BACKGROUND: Proper proprioceptive and neuromuscular control is crucial for the overhead athlete's performance. The aim of the present study was to evaluate the shoulder joint position sense (JPS) levels in overhead throwing athletes. The secondary aim was to confront the proprioceptive abilities with glenohumeral adaptive changes and pathologies among athletes. METHODS: Ninety professional handball players and 32 healthy volunteers were recruited. JPS levels were measured by an electronic goniometer and expressed as values of an active reproduction of the joint position (ARJP) and as error of ARJP (EARJP) in 3 different reference positions for each movement (abduction and flexion at 60°, 90°, and 120°; internal [IR] and external rotation [ER] at 30°, 45°, and 60°). RESULTS: Side-to-side differences revealed significantly better values of EARJP for the throwing shoulders in abduction at 90° and 120°, flexion at 90° and 120°, IR at 60°, and ER at 30° and 60° compared with the nonthrowing shoulders. Handball players showed significantly better proprioceptive levels in their throwing shoulder compared to the dominant shoulder of the control group in abduction at 90° (P = .037) and 120° (P = .001), flexion at 120° (P = .035), IR at 60° (P = .045), and in ER at 60° (P = .012). DISCUSSION: Handball players present superior shoulder JPS in their dominant throwing shoulder at high range of motion angles when compared to a nonathlete population and to their own nondominant shoulder.
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Lesões do Ombro , Articulação do Ombro , Esportes , Humanos , Estudos Prospectivos , Atletas , Propriocepção , Amplitude de Movimento ArticularRESUMO
INTRODUCTION: Cervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation. METHODS AND ANALYSIS: This trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio. The study is conducted at tertiary perinatal care departments in Poland. It will include patients with cervical insufficiency with the fetal membranes visible in the open cervical canal or protruding into the vagina between 16+0 and 23+6 weeks of pregnancy. They will be randomised into two arms: emergency single-level cerclage with vaginal progesterone or double-level cerclage with vaginal progesterone. All will be administered antibiotics and indomethacin. The primary outcome is the rate of deliveries below 34+0 weeks of gestation, while secondary outcomes include gestational age at delivery, neonatal outcomes, maternal outcomes according to the Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth and cerclage procedure complications. The planned number of participants according to the power analysis is 78. ETHICS AND DISSEMINATION: The study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. It was created according to the requirements of the Declaration of Helsinki for Medical Research involving Human Subject. Ethical approval was obtained from the Ethics Committee of the Centre of Postgraduate Medical Education (no. 1/2022). The study protocol was approved and published by ClinicalTrials.gov (posted on 24 February 2022). All participants gave a written informed consent. After completion of the study its results will be published in a peer-reviewed English language journal. TRIAL REGISTRATION: NCT05268640.
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Cerclagem Cervical , Nascimento Prematuro , Gravidez , Feminino , Humanos , Recém-Nascido , Progesterona , Nascimento Prematuro/prevenção & controle , Nascimento Prematuro/etiologia , Cerclagem Cervical/efeitos adversos , Cerclagem Cervical/métodos , Colo do Útero , Suturas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
To evaluate the prenatal course and perinatal outcome of fetuses with bronchopulmonary sequestration (BPS) managed expectantly or using minimally invasive methods. This was a retrospective study of 29 fetuses with suspected BPS managed between 2010 and 2021 in three fetal medicine centers in Poland. Medline was searched to identify cases of BPS managed expectantly or through minimally-invasive methods. In 16 fetuses with BPS, there was no evidence of cardiac compromise. These fetuses were managed expectantly. Thirteen hydropic fetuses with BPS qualified for intrauterine intervention: a thoraco-amniotic shunt (TAS) was inserted in five fetuses, laser coagulation of the feeding vessel was performed in seven cases, and one fetus had combined treatment. In the combined data from the previous and the current study of various percutaneous interventions for BPS associated with hydrops, the survival rate was 91.2% (31/34) for TAS, 98.1% (53/54) for laser coagulation, and 75% (3/4) for intratumor injection of sclerosant. After taking into account cases with available data, the rate of preterm birth before 37 weeks in the group treated with laser coagulation was 14.3% (7/49) compared to 84.6% (22/26) in the group treated with TAS. The need for postnatal sequestrectomy was lower in the group of fetuses treated with laser coagulation 23.5% (12/51) in comparison to fetuses treated with TAS 84% (21/26). In fetuses with BPS without hydrops, progression of the lesion's volume, leading to cardiac compromise, is unlikely. In hydropic fetuses with BPS, intrauterine therapy using minimally invasive methods prevents fetal demise. Both, the rate of preterm birth and the need for postnatal surgery is significantly lower in the group treated with laser coagulation compared to the group treated with TAS.
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INTRODUCTION: Shoulder stability is secured by dynamic and static stabilizers. Rotator cuff is responsible for dynamic stabilization. In cases of shoulder instability their activity is disturbed. Capsulolabral repair restores mainly static stabilization. This surgery treatment technique of shoulder instability was first described by Bankart in 1923. His idea, with further modifications, is commonly used up to this day. Evaluation of muscle shoulder recovery after stabilization should be one of the important criteria to allow patient to return to sport and work. However, not much isokinetic assessment after capsulolabral repair was described. The aim of this study were the following: the comparative assessment of the shoulder rotatory strength in patients following arthroscopic capsulolabral repair of unilateral anterior traumatic instability and clinical assessment with comparison of pre and post-operative results. MATERIAL AND METHODS: Forty-five patients, 14 women and 31 men, with an average follow-up of 4.4 years were tested bilaterally for internal and external rotation strength at four angular velocities. ASES and UCLA tests were collected before and after surgery. RESULTS: The values of peak moment and muscle power parameters were slightly lower for an operated shoulder in comparison to a healthy shoulder for the external rotation. Total work parameter in external rotation was significantly lower for the operated shoulder in comparison to the non-operated side. The internal/external muscle group balance was lower for the operated shoulder in comparison to reference values in the women group. Furthermore, both ASES and UCLA scores were significantly higher after operation. CONCLUSIONS: After arthroscopic capsulolabral shoulder stabilization, slight differences in isokinetic evaluation, especially in external shoulder rotation, occur. It affects rotators muscle balance. In functional evaluation significant improvement in shoulder function occurs.
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Instabilidade Articular , Luxação do Ombro , Articulação do Ombro , Masculino , Humanos , Feminino , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia , Ombro , Articulação do Ombro/cirurgia , Amplitude de Movimento Articular/fisiologia , Artroscopia/métodos , Luxação do Ombro/cirurgiaRESUMO
A prelabor rupture of membranes (PROM) and its subtypes, preterm PROM (pPROM) and term PROM (tPROM), are associated with disturbances in the hemostatic system and angiogenesis. This study was designed to demonstrate the role of single nucleotide polymorphisms (SNPs), localized in CSF2 (rs25881), FLT1 (rs722503), TFPI (C-399T) and TLR9 (rs352140) genes, in PROM. A population of 360 women with singleton pregnancy consisted of 180 PROM cases and 180 healthy controls. A single-SNP analysis showed a similar distribution of genotypes in the studied polymorphisms between the PROM or the pPROM women and the healthy controls. Double-SNP TT variants for CSF2 and FLT1 polymorphisms, CC variants for TLR9 and TFPI SNPs, TTC for CSF2, FLT1 and TLR9 polymorphisms, TTT for FLT1, TLR9 and TFPI SNPs and CCCC and TTTC complex variants for all tested SNPs correlated with an increased risk of PROM after adjusting for APTT, PLT parameters and/or pregnancy disorders. The TCT variants for the CSF2, FLT1 and TLR9 SNPs and the CCTC for the CSF2, FLT1, TLR9 and TFPI polymorphisms correlated with a reduced risk of PROM when corrected by PLT and APTT, respectively. We concluded that the polymorphisms of genes, involved in hemostasis and angiogenesis, contributed to PROM.
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Ruptura Prematura de Membranas Fetais/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Lipoproteínas/genética , Polimorfismo de Nucleotídeo Único , Receptor Toll-Like 9/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Adulto , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Idade Materna , Gravidez , Adulto JovemAssuntos
Complicações na Gravidez/prevenção & controle , Cuidado Pré-Natal/normas , Ultrassonografia Pré-Natal/normas , Feminino , Ginecologia/normas , Humanos , Capacitação em Serviço/normas , Programas Nacionais de Saúde/normas , Obstetrícia/normas , Polônia , Guias de Prática Clínica como Assunto , Gravidez , Sociedades Médicas/normasRESUMO
Nicotine decreases food intake, and smokers often report that they smoke to control their weight. To see whether similar phenomena could be observed in the model organism Caenorhabditis elegans, we challenged drug-naïve nematodes with a chronic low (0.01 mM) and high (1 mM) nicotine concentration for 55 h (from hatching to adulthood). After that, we recorded changes in their behavior in a nicotine gradient, where they could choose a desired nicotine concentration. By using a combination of behavioral and morphometric methods, we found that both nicotine and food modulate worm behavior. In the presence of food (E. coli OP50) the nematodes adapted to the low nicotine concentration, when placed in the gradient, chose a similar nicotine concentration like C. elegans adapted to the high nicotine concentration. However, in the absence of food, the nematodes adapted to the low nicotine concentration, when placed in the gradient of this alkaloid, chose a similar nicotine concentration like naïve worms. The nematodes growing up in the presence of high concentrations of nicotine had a statistically smaller body size, compared to the control condition, and the presence of food did not cause any enhanced slowing movement. These results provide a platform for more detailed molecular and cellular studies of nicotine addiction and food intake in this model organism.
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Caenorhabditis elegans/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Nicotina/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Atividade Motora/efeitos dos fármacos , Nicotina/farmacologiaRESUMO
PURPOSE: Glenohumeral range of motion adaptations may affect throwing athletes and contribute to shoulder injury. The purpose of this study was to evaluate shoulder rotation deficits among elite professional handball players and its correlation to the presence of shoulder pain and morphological changes. METHODS: Eighty-seven elite professional handball players and 41 healthy non-athlete volunteers participated in the study. Evaluations included measurement of range of internal and external rotation, total arch of motion, identification of shoulder pain and ultrasound scan for diagnosis of rotator cuff tears and internal impingement. RESULTS: Glenohumeral rotational deficits (>20-25°) were found among 11 players group (13%). The throwing shoulders in the players group showed a decrease in internal rotation and an increase in external rotation with significantly larger ranges among players compared to the non-athlete group. Internal rotation deficit >20° was associated with higher incidence of shoulder pain among players. Both internal rotation deficits (>25°) and total arch of motion deficit (>20°) co-existed with higher incidence of internal impingement. Shoulder pain was common (36/97-41%) and was associated with decreased external rotation and total arch of motion. Internal impingement (found in 13/87-15%) correlated with decreased rotation ranges and a greater deficit in total arch of motion, whereas higher gain in external rotation correlated with a partial rotator cuff tear (found in 12/87-14%). CONCLUSIONS: Shoulder pathologies and problems commonly affected the group of handball players. Greater glenohumeral rotational deficits in throwing shoulders of handball players correlate with shoulder pain and internal impingement, while increased external rotation with partial rotator cuff tears. Such deficits affect 13% of the athlete population. Major clinical relevance of the study is to monitor handball players' shoulders both clinically and by proper imaging. Evaluation of range of rotation seems to identify shoulders at risk of the pathology. LEVEL OF EVIDENCE: Cross-Sectional study with control group, Level II.
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Traumatismos em Atletas/fisiopatologia , Lesões do Ombro/fisiopatologia , Articulação do Ombro/fisiopatologia , Dor de Ombro/fisiopatologia , Adaptação Fisiológica , Adolescente , Adulto , Traumatismos em Atletas/diagnóstico por imagem , Estudos Transversais , Humanos , Masculino , Amplitude de Movimento Articular , Rotação , Lesões do Manguito Rotador/diagnóstico por imagem , Síndrome de Colisão do Ombro/diagnóstico por imagem , Lesões do Ombro/diagnóstico por imagem , Articulação do Ombro/diagnóstico por imagem , Dor de Ombro/etiologia , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: Vasculitides are commonly unrecognized causes of coronary stenosis and myocardial ischemia. We report on a 24-year old patient with Takayasu's arteritis who underwent urgent percutaneous coronary intervention, suffered from symptomatic restenosis of the left main coronary artery during standard immunosuppressive therapy. CASE PRESENTATION: A 24-year old woman was referred for coronary angiography because of typical progressive angina pectoris. On bicycle ergometry, there were both reproducible symptoms and deep ST segment depressions on precordial leads. Semi-selective angiography of the left coronary artery revealed high-grade ostial stenosis. Because of persistent angina pectoris and electrocardiographic signs of acute myocardial ischemia, immediate percutaneous coronary angioplasty with subsequent implantation of an everolimus-eluting stent was performed. This intervention was performed with excellent angiographic results. Because of several concomitant criteria including hypoechogenicity on postprocedural intravascular ultrasonography, the diagnosis of Takayasu's disease was made. The patient was treated with prednisolone and cyclophosphamide for 5 months. Because of recurrent angina pectoris, another coronary angiography was performed, which revealed high-grade in-stent-restenosis. Immunomodulatory therapy was switched to high-dose prednisolone and the anti-IL-6 receptor antagonist tocilizumab. The high-grade in-stent-restenosis persisted, and aortocoronary bypass graft surgery was performed with two saphenous vein grafts to the left anterior descending and circumflex artery. Since then, the patient has been doing well for 2 years. CONCLUSION: In cases of treatment refractoriness during standard immunosuppressive therapy, more recently developed biological compounds may offer an alternative strategy.
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Revascularização Miocárdica/métodos , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/cirurgia , Adulto , Feminino , Humanos , Imunossupressores/farmacologia , Recidiva , Arterite de Takayasu/tratamento farmacológico , Adulto JovemRESUMO
OBJECTIVES: The aim of the study was to evaluate the relationship between the concentrations of substances released by the placenta: placental growth factor (PIGF), pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) and the risk of early and late preeclampsia (PE) and intrauterine fetal growth restriction (IUGR). MATERIAL AND METHODS: A total of 180 pregnant women between 11+0 and 13+6 weeks gestation were recruited for a case-control study Twenty-two patients suffered from early PE, 29 patients from late PE. Data analyzed during the study included maternal histoty and concentrations of PAPP-A, PlGF beta-hCG. RESULTS: The multiple of the median (MoM) value of the PAPP-A concentrations was 1.01 in the control group (interquartile range (1QR), 0.65-1.55), 0.67 (1QR, 0.382-0.82) in the group of patients with early preeclampsia and 0.74 (IQ, 0.33-1.09) in the group of patients suffering from late preeclampsia. MoM value of the PIGF concentrations was 1.21 in the control group (IQR, 0.93-1.57), 0.62 (IQR, 0.51-0.96) in the group of patients with early preeclampsia and 0.92 (lQR, 0.63-1.09) in the group of patients suffering from late preeclampsia. MoM value of beta-hCG concentrations was 1.14 in the control group (IQR, 0.75-1.49), 1.08(IQR, 0.74-1.23) in the group of patients with early preeclampsia and 1,25(IQR, 1,05-1,49) in the group of patients suffering from late preeclampsia. The performance of screening was determined by the areas under the curve and detection rates, with a fixed false-positive rate of 10%. CONCLUSIONS: Decreased levels of PAPP-A and PIGF are related to an increased risk of preeclampsia and its complications.
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Gonadotropina Coriônica Humana Subunidade beta/sangue , Retardo do Crescimento Fetal/diagnóstico , Pré-Eclâmpsia/diagnóstico , Proteína Plasmática A Associada à Gravidez/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal/sangue , Humanos , Pré-Eclâmpsia/sangue , GravidezAssuntos
Capacitação em Serviço/normas , Complicações na Gravidez/prevenção & controle , Cuidado Pré-Natal/normas , Ultrassonografia Pré-Natal/normas , Feminino , Ginecologia/normas , Humanos , Programas Nacionais de Saúde/normas , Obstetrícia/normas , Polônia , Guias de Prática Clínica como Assunto , Gravidez , Primeiro Trimestre da Gravidez , Garantia da Qualidade dos Cuidados de Saúde/normas , Sociedades Médicas/normasRESUMO
PURPOSE: The purpose of the study was clinical and advanced biomechanical evaluation of shoulder function with respect to rotator cuff (RC) integrity following repair. METHODS: This was a retrospective study of 111 cases with solid single row rotator cuff repair and a minimal one-year follow-up. The RC repair was performed as an open procedure in 42 patients, arthroscopically assisted in 34 and fully arthroscopic in 48 cases. Evaluation protocol included ultrasound evaluation of the RC integrity, clinical evaluation using shoulder scores and advanced biomechanical evaluation (isometric and the isokinetic strength testing). RESULTS: Ultrasound evaluation revealed complete retear in 16%, partial retear in 10% and intact repair in 74% of the cases. Isometric testing of flexion and abduction had shown that shoulders with complete retear were weaker by 45% compared to those with full tendon healing. Isokinetic testing revealed 29-43% deficits in peak external rotation torque comparing complete retear vs. normal healing. Patients' ability to generate shoulder power and withstand a load proved to be lower in circumstances of a complete lack of healing (40-43% and 34-55%, respectively). Partial retears did not have a negative impact on the biomechanical properties of shoulders. Surprisingly, there were no significant differences in the shoulder scores related to the quality of healing. In terms of patient satisfaction the results were good and the patients declared themselves better in all cases, no matter what quality of healing had been recorded ultimately. CONCLUSIONS: According to the results of this research rotator cuff integrity after open or arthroscopic repair does not seem to affect clinical scores. Recurrent tears may result in lower muscle performance in terms of active motion, strength and endurance. Advanced shoulder testing may be essential in assessing the patients' ability to return to sports or heavy labour.
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Artroscopia/métodos , Lesões do Manguito Rotador , Manguito Rotador/cirurgia , Articulação do Ombro/fisiopatologia , Articulação do Ombro/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Resistência Física/fisiologia , Amplitude de Movimento Articular/fisiologia , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos , Manguito Rotador/fisiopatologia , Falha de Tratamento , Cicatrização/fisiologiaRESUMO
Loss of Abcc6 gene expression was identified to be responsible for dystrophic calcification of the heart (DCC) or vessels after acute injury in several strains of laboratory mice. This calcification shares features with osteogenesis and may involve osteogenic factors. Tissue expression of osteopontin (Opn) and 11 osteogenic transcription factors were studied in vivo in mouse models for DCC and in vitro using luciferase reporter gene assays. Compared with DCC-resistant C57BL/6 mice, a significant increase in Opn transcription was demonstrated in necrotic lesions of both DCC-susceptible C3H/He and B6.C3H(Dyscalc1) congenic mice at day 3 after injury. Significant increases in gene expression were also demonstrated for the transcription factors runt domain-containing transcription factor 2 (Runx2), vitamin D receptor (Vdr), SRY (sex-determining region Y)-box 9 protein, and Nfkb1 in C3H/He mice versus C57BL/6 controls. However, only Runx2 remained significantly increased in the B6.C3H(Dyscalc1) congenic mice, which carry only the Dyscalc1 locus with functional Abcc6 deletion on a C57BL/6 genetic background. Luciferase assay use increased Opn promoter activity, which was demonstrated after overexpression of Runx2. A poly-T stretch insertion was identified to stabilize the binding of Runx2, thus significantly enhancing Opn promoter activity. This Runx2-mediated activation was further enhanced by cotransfection with Vdr. Our data suggest a key role of Runx2 in the regulation of Opn in a model of cardiovascular calcification and demonstrate a synergistic cooperation of Runx2 and Vdr.
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Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Osteopontina/metabolismo , Receptores de Calcitriol/metabolismo , Calcificação Vascular/metabolismo , Transportadores de Cassetes de Ligação de ATP/deficiência , Animais , Biomarcadores/metabolismo , Western Blotting , Feminino , Imuno-Histoquímica , Medições Luminescentes , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Osteochondroma is one of the most frequent benign bone tumors in children. Its incidence is hard to determine because this tumor usually is asymptomatic. These tumors may present as solitary, nonhereditary lesions or as hereditary multiple osteochondromas that are inherited in an autosomal dominant manner. Although osteochondromas are usually asymptomatic, significant symptoms may occur because of complications such as bone fracture, bone deformation, or joint problems. The tumor may also mechanically compress nerves or vessels. Osteochondromas growing inwardly may cause injury to internal organs. The authors present a preterm (34 weeks of corrected gestational age) neonate in whom osteochondroma, although histologically benign, caused death because of its size and location. Prenatal ultrasound imaging performed during the third trimester of pregnancy showed bilateral hydrothorax and hydroperitoneum as well as heterogeneous parenchymal area on the right side of the thorax. After birth, the neonate's condition was extremely severe. Although intensive and multidirectional treatment was applied, the condition of the infant continued to deteriorate and he died 26 h after birth. The autopsy confirmed presence of the tumor - osteochondroma - that caused total mediastinal shift with significant hypoplasia of both lungs and with signs of significant compression of the superior and inferior vena cava.
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Osteocondroma/congênito , Osteocondroma/patologia , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Masculino , Osteocondroma/diagnóstico por imagem , Gravidez , Radiografia Torácica , Ultrassonografia Pré-NatalRESUMO
Antiproliferative factor (APF) is a potent frizzled protein 8-related sialoglycopeptide inhibitor of bladder epithelial cell proliferation that mediates its activity by binding to cytoskeletal associated protein 4 in the cell membrane. Synthetic asialylated APF (as-APF) (Galß1-3GalNAcα-O-TVPAAVVVA) was previously shown to inhibit both normal bladder epithelial as well as T24 bladder carcinoma cell proliferation and heparin-binding epidermal growth factor-like growth factor (HB-EGF) production at low nanomolar concentrations, and an L: -pipecolic acid derivative (Galß1-3GalNAcα-O-TV-pipecolic acid-AAVVVA) was also shown to inhibit normal bladder epithelial cell proliferation. To better determine their spectrum of activity, we measured the effects of these APF derivatives on the proliferation of cells derived from additional urologic carcinomas (bladder and kidney), non-urologic carcinomas (ovary, lung, colon, pancreas, and breast), and melanomas using a (3)H-thymidine incorporation assay. We also measured the effects of as-APF on cell HB-EGF and matrix metalloproteinase (MMP2) secretion plus cell invasion, using qRT-PCR, Western blot and an in vitro invasion assay. L: -pipecolic acid as-APF and/or as-APF significantly inhibited proliferation of each cell line in a dose-dependent manner with IC(50)'s in the nanomolar range, regardless of tissue origin, cell type (carcinoma vs. melanoma), or p53 or ras mutation status. as-APF also inhibited HB-EGF and MMP2 production plus in vitro invasion of tested bladder, kidney, breast, lung, and melanoma tumor cell lines, in a dose-dependent manner (IC(50) = 1-100 nM). Synthetic APF derivatives are potent inhibitors of urologic and non-urologic carcinoma plus melanoma cell proliferation, MMP2 production, and invasion, and may be useful for development as adjunctive antitumor therapy(ies).
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Carcinoma/tratamento farmacológico , Glicoproteínas/farmacologia , Melanoma/tratamento farmacológico , Receptores de Superfície Celular/metabolismo , Carcinoma/metabolismo , Carcinoma/patologia , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Invasividade Neoplásica , Prognóstico , Sialoglicoproteínas/metabolismo , Bexiga Urinária/metabolismo , Bexiga Urinária/patologiaRESUMO
Human α-defensin 5 (HD5, HD5(ox) to specify the oxidized and disulfide linked form) is a 32-residue cysteine-rich host-defense peptide, expressed and released by small intestinal Paneth cells, that exhibits antibacterial activity against a number of Gram-negative and -positive bacterial strains. To ascertain the contributions of its disulfide array to structure, antimicrobial activity, and proteolytic stability, a series of HD5 double mutant peptides where pairs of cysteine residues corresponding to native disulfide linkages (Cys(3)-Cys(31), Cys(5)-Cys(20), Cys(10)-Cys(30)) were mutated to Ser or Ala residues, overexpressed in E. coli, purified, and characterized. A hexa mutant peptide, HD5[Ser(hexa)], where all six native Cys residues are replaced by Ser residues, was also evaluated. Removal of a single native S-S linkage influences oxidative folding and regioisomerization, antibacterial activity, Gram-negative bacterial membrane permeabilization, and proteolytic stability. Whereas the majority of the HD5 mutant peptides show low micromolar activity against Gram-negative E. coli ATCC 25922 in colony counting assays, the wild-type disulfide array is essential for low micromolar activity against Gram-positive S. aureus ATCC 25923. Removal of a single disulfide bond attenuates the activity observed for HD5(ox) against this Gram-positive bacterial strain. This observation supports the notion that the HD5(ox) mechanism of antibacterial action differs for Gram-negative and Gram-positive species [Wei et al. (2009) J. Biol. Chem. 284, 29180-29192] and that the native disulfide array is a requirement for its activity against S. aureus.