Elevación crónica de creatincinasa / Chronic creatinine elevation

Las miopatías son entidades en las que se produce afectación musculo esquelética con elevación de creatincinasa en suero. La Enfermedad de Addison y la Hipertermia Maligna constituyen causas poco comunes de miopatía. La Enfermedad de Addison corresponde a una insuficiencia suprarrenal primaria producida por un déficit de glucocorticoides, mineral corticoides y andrógenos por destrucción de la corteza suprarrenal, cuyos síntomas son inespecíficos y el tratamiento es con hidrocortisona. La Hipertermia Maligna se produce por una alteración genética en la que los anestésicos inhalados y los relajantes musculares desencadenan una hipertermia progresiva, con rigidez muscular, taquicardia, hipotensión, rabdomiolisis, y coagulación intravascular diseminada (AU)

Myopathy is a disease that affects the musculoskeletal system with elevated serum creatinine. Addison’s Disease and Malignant Hyperthermia, are rare causes of myopathy. Addison’s disease, also known as primary adrenal insufficiency, occurs when the adrenal gland does not produce enough glucocorticoids, mineralocorticoids and androgens because of the destruction of the adrenal cortex. Symptoms are non-specific and it is treated with hydrocortisone. Malignant Hyperthermia is a genetic disorder, in which inhaled anaesthetics and muscle relaxants, trigger progressive hyperthermia with muscle rigidity, tachycardia, hypotension, rhabdomyolysis, and disseminated intravascular coagulation (AU)

Ubiquitous mitochondrial creatine kinase is overexpressed in the conditioned medium and the extract of LNCaP lineaged androgen independent cell lines and facilitates prostate cancer progression.

BACKGROUND: Androgen independent prostate cancer (AIPC) is not responsive to androgen ablation therapy. The biomarkers of AIPC are lack. Numerous proteomics studies have focused on finding new markers of AIPC and exploring their possible functions, but little is known about the difference between conditioned medium (CM) from AIPC and androgen dependent prostate cancer (ADPC) cells. METHODS: We performed a proteome analysis of CM from LNCaP, C4-2, and C4-2B cells by a two dimensional electrophoresis based technology. Western blots and immunohistochemical studies were employed to explore the expression pattern of the identified protein in prostate cancer cell lines and clinical specimens, respectively. Then we examined the possible roles and mechanisms of the ubiquitous mitochondrial creatine kinase (uMtCK) in vitro. RESULTS: Besides prostate specific antigen (PSA) and insulin-like growth factor binding protein-2 (IGFBP2), uMtCK was identified in the CM of AIPC cells. uMtCK was up-regulated in AIPC cells and in human prostate cancer tissues at WHO grade III. Stably transfected exogenous uMtCK showed a growth promoting effect rather than mock vector in LNCaP cells, with or without bicalutamide in culture medium. Further assays showed that higher degrees of ROS generation and Akt signaling pathway activation in LNCaP-uMtCK than in LNCaP-neo cells. CONCLUSIONS: We showed that uMtCK could be easily detected in CM of LNCaP lineaged AIPC cells. Exogenous uMtCK in LNCaP cells surprisingly contributed to overproduction of ROS, activation of Akt signaling pathway and more aggressive phenotypes including androgen independence development.

Progressive decrease of phosphocreatine, creatine and creatine kinase in skeletal muscle upon transformation to sarcoma.

In vertebrates, phosphocreatine and ATP are continuously interconverted by the reversible reaction of creatine kinase in accordance with cellular energy needs. Sarcoma tissue and its normal counterpart, creatine-rich skeletal muscle, are good source materials to study the status of creatine and creatine kinase with the progression of malignancy. We experimentally induced sarcoma in mouse leg muscle by injecting either 3-methylcholanthrene or live sarcoma 180 cells into one hind leg. Creatine, phosphocreatine and creatine kinase isoform levels decreased as malignancy progressed and reached very low levels in the final stage of sarcoma development; all these parameters remained unaltered in the unaffected contralateral leg muscle of the same animal. Creatine and creatine kinase levels were also reduced significantly in frank malignant portions of human sarcoma and gastric and colonic adenocarcinoma compared with the distal nonmalignant portions of the same samples. In mice, immunoblotting with antibodies against cytosolic muscle-type creatine kinase and sarcomeric mitochondrial creatine kinase showed that both of these isoforms decreased as malignancy progressed. Expressions of mRNA of muscle-type creatine kinase and sarcomeric mitochondrial creatine kinase were also severely downregulated. In human sarcoma these two isoforms were undetectable also. In human gastric and colonic adenocarcinoma, brain-type creatine kinase was found to be downregulated, whereas ubiquitous mitochondrial creatine kinase was upregulated. These significantly decreased levels of creatine and creatine kinase isoforms in sarcoma suggest that: (a) the genuine muscle phenotype is lost during sarcoma progression, and (b) these parameters may be used as diagnostic marker and prognostic indicator of malignancy in this tissue.

Fascitis eosinofílica, respuesta favorable al tratamiento con ciclosporina A / Eosynophilic fasciitis. Favorable response to treatment with Cyclosporin A

Introducción: La fascitis eosinofílica (FE) es una enfermedad de origen desconocido, caracterizada por induración de la piel, debido a inflamación de las fascias del tejido conjuntivo. Afecta principalmente a las extremidades y se acompaña de elevación de inmunoglobulinas y eosinofilia periférica. Objetivo: Evaluar la eficacia de ciclosporina A en pacientes con FE con resistencia al tratamiento convencional con glucocorticoides. Pacientes y método: Presentamos 3 pacientes con manifestaciones clínicas y serológicas de FE que tuvieron resistencia al tratamiento estándar con glucocorticoides (30 a 50 mg/día, durante un período de hasta 8 meses). Las manifestaciones clínicas principales fueron: induración de la piel de las extremidades y el tronco que se acompañó de eosinofilia periférica y elevación de la creatincinasa. Histológicamente se observó un engrosamiento con intensa inflamación linfocitaria de las fascias. Resultados: Todos los pacientes fueron tratados con ciclosporina A, a dosis de 5 a 7 mg/kg/día con una rápida mejoría clínica (2 meses). El tratamiento condujo, en todos los casos, a una remisión clínica que permitió reducir e incluso retirar la ciclosporina A durante el seguimiento. Conclusiones: La ciclosporina A parece una alternativa terapéutica eficaz en el tratamiento de pacientes con FE resistente a glucocorticoides (AU)

Introduction: Eosinophilic fasciitis (EF) is a disease of unknown aetiology characterized by cutaneous swelling and indurations. The disease affects predominantly the extremities and usually show an elevation of serum immunoglobulins, and eosinophilia. Objective: Evaluation of the efficacy of cyclosporine A as a therapeutic alternative in patients with EF refractory to steroids. Patients and method: We report 3 patients with clinical, laboratory and pathologic characteristics of EF who did not show a satisfactory response to steroids treatment. All patients disclosed scleroderma-like signs with orange skin, groove sign, and indurations of the affected extremities associated to peipheral eosinophilia and increased creatine-kinase. Epidermis histological findings were normal and intense linfocitary inflammation of the fascia was observed in all patients’ biopsies. All patients were treated for average of 8 months with prednisone 30-50 mg daily with an insufficient clinical response. Results: Patients started on cyclosporine A 5-7 mg/kg/day, showing a fast improvement (2 months). The treatment induces a clinical remission that permits to reduce or even stops the cyclosporine A treatment during follow-up. Conclusions: It seems that cyclosporine A may be a effective therapeutic alternative in patients with EF refractory to steroids (AU)