RESUMEN
Pancreatic ductal adenocarcinoma (PDAC) remains a disease with extremely poor prognosis and limited effective available treatment. Differential expression of miRNAs isolated from tumor tissue has been proposed as a marker for tumor diagnosis, progression, and prognosis. Nevertheless, the prognostic value of miRNAs expression in PDACs for patient outcome still remains unclear. Expression of 7 selected miRNAs, isolated from FFPE samples of 54 PDAC patients, was quantified using RT-qPCR. The relationship of miRNA expression levels with tumor histology, clinicopathological characteristics, patient overall survival (OS), and progress-free survival (PFS), was subsequently evaluated. Overexpression of miR-21, miR-155, and miR-210 was observed in PDACs (up to 72.62, 232.36, and 181.38-fold, respectively), in comparison with non-neoplastic tissues. On the other hand, miR-96 and miR-217 were significantly downregulated in PDACs (up to one hundred times). No differences were, however, noticed between cancer and normal tissues for the expression levels of miR-148a and miR-196a. On the other hand, expression levels of all 7 miRNAs failed to demonstrate a significant correlation with parameters of tumor progression, such as tumor stage, grade, nodal involvement, perineural, and vascular invasion. The positive correlation of miR-210 levels was, however, observed with patient age (ρ=0.35). Additionally, miR-148a and miR-217 expressions have shown a positive association with tubular tumor growth pattern (ρ=0.39; ρ=0.28). The negative correlation of miR-148a values was also demonstrated with dissociative growth pattern and nuclear atypia (ρ=-0.30; ρ=-0.27). Finally, no statistically significant correlation could be demonstrated with the expression levels of all 7 tested miRNAs and PDAC patient survival; neither for OS nor for PFS (p>0.05). Our data have confirmed abnormal miRNAs expression in PDACs in comparison with adjacent non-neoplastic tissue. On the other hand, no correlation was discovered between miRNA expression and parameters of tumor progression. We have found a significant association between histologic tumor growth patterns and miRNA expression, making this work the first study, which analyses this aspect of PDAC. Finally, in our group of patients, no relationship of miRNA levels and patient prognosis could be demonstrated. Therefore, further investigation is required to evaluate the predictive and prognostic potential of miRNAs in a clinical setting.
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Carcinoma Ductal Pancreático , MicroARNs/genética , Neoplasias Pancreáticas , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pancreáticas/genética , PronósticoRESUMEN
Acute liver failure (ALF) is known for extremely high mortality rate, the result of widespread damage of hepatocytes. Orthotopic liver transplantation is the only effective therapy but its application is limited by the scarcity of donor organs. Given the importance in the liver biology of Wnt/beta-catenin signaling pathway, we hypothesized that its stimulation could enhance hepatocyte regeneration and attenuate the course of thioacetamide (TAA)-induced ALF in Lewis rats. Chronic treatment with Wnt agonist was started either immediately after hepatotoxic insult ("early treatment") or when signs of ALF had developed ("late treatment"). Only 23 % of untreated Lewis rats survived till the end of experiment. They showed marked increases in plasma alanine aminotransferase (ALT) activity and bilirubin and ammonia (NH3) levels; plasma albumin decreased significantly. "Early" and "late" Wnt agonist treatment raised the final survival rate to 69 % and 63 %, respectively, and normalized ALT, NH3, bilirubin and albumin levels. In conclusion, the results show that treatment with Wnt agonist attenuates the course of TAA-induced ALF in Lewis rats, both with treatment initiated immediately after hepatotoxic insult and in the phase when ALF has already developed. Thus, the pharmacological stimulation of Wnt/beta-catenin signaling pathway can present a new approach to ALF treatment.
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Fallo Hepático Agudo/tratamiento farmacológico , Hígado/efectos de los fármacos , Proteínas Wnt/agonistas , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo , Animales , Evaluación Preclínica de Medicamentos , Hígado/metabolismo , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/metabolismo , Masculino , Ratas Endogámicas Lew , TioacetamidaRESUMEN
Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent complication of diabetes, obesity and hypertension. Since it is typically undetected for long periods, it often progresses to end-stage renal disease. CKD is characterized by the development of progressive glomerulosclerosis, interstitial fibrosis and tubular atrophy along with a decreased glomerular filtration rate. This is associated with podocyte injury and a progressive rise in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin receptor type A (ET(A)) promotes renal cell injury, inflammation, and fibrosis which finally lead to proteinuria, it is not surprising that ET(A) receptors antagonists have been proven to have beneficial renoprotective effects in both experimental and clinical studies in diabetic and non-diabetic CKD. Unfortunately, fluid retention encountered in large clinical trials in diabetic CKD led to the termination of these studies. Therefore, several advances, including the synthesis of new antagonists with enhanced pharmacological activity, the use of lower doses of ET antagonists, the addition of diuretics, plus simply searching for distinct pathological states to be treated, are promising targets for future experimental studies. In support of these approaches, our group demonstrated in adult subtotally nephrectomized Ren-2 transgenic rats that the addition of a diuretic on top of renin-angiotensin and ET(A) blockade led to a further decrease of proteinuria. This effect was independent of blood pressure which was normalized in all treated groups. Recent data in non-diabetic CKD, therefore, indicate a new potential for ET(A) antagonists, at least under certain pathological conditions.
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Diuréticos/uso terapéutico , Antagonistas de los Receptores de la Endotelina A/uso terapéutico , Receptor de Endotelina A/metabolismo , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/prevención & control , Animales , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Diuréticos/farmacología , Antagonistas de los Receptores de la Endotelina A/farmacología , Endotelina-1/antagonistas & inhibidores , Endotelina-1/metabolismo , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiologíaRESUMEN
We assessed the effect of the previously uncovered gap junction protein alpha 8 (Gja8) mutation present in spontaneously hypertensive rat - dominant cataract (SHR-Dca) strain on blood pressure, metabolic profile, and heart and renal transcriptomes. Adult, standard chow-fed male rats of SHR and SHR-Dca strains were used. We found a significant, consistent 10-15 mmHg decrease in both systolic and diastolic blood pressures in SHR-Dca compared with SHR (P<0.01 and P<0.05, respectively; repeated measures analysis of variance (ANOVA)). With immunohistochemistry, we were able to localize Gja8 in heart, kidney, aorta, liver, and lungs, mostly in endothelium; with no differences in expression between strains. SHR-Dca rats showed decreased body weight, high-density lipoprotein cholesterol concentrations and basal insulin sensitivity in muscle. There were 21 transcripts common to the sets of 303 transcripts in kidney and 487 in heart showing >1.2-fold difference in expression between SHR and SHR-Dca. Tumor necrosis factor was the most significant upstream regulator and glial cell-derived neurotrophic factor family ligand-receptor interactions was the common enriched and downregulated canonical pathway both in heart and kidney of SHR-Dca. The connexin 50 mutation L7Q lowers blood pressure in the SHR-Dca strain, decreases high-density lipoprotein cholesterol, and leads to substantial transcriptome changes in heart and kidney.
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Presión Sanguínea/fisiología , Conexinas/genética , Conexinas/metabolismo , Hipertensión/genética , Hipertensión/metabolismo , Mutación/fisiología , Animales , Redes Reguladoras de Genes/fisiología , Corazón/fisiología , Riñón/metabolismo , Hígado/metabolismo , Masculino , Ratas , Ratas Endogámicas SHRRESUMEN
Surgical treatment is not commonly recommended in the management of autoimmune pancreatitis. The article describes a dilemma in diagnostics and treatment of a 68-year old man with the mass in the head of the pancreas that mimicked pancreatic cancer and that was diagnosed as a type 1 autoimmune pancreatitis (IgG4-related pancreatitis) after a surgical resection. Diagnosis of the autoimmune pancreatitis is a real clinical challenge, as in the current diagnostic criteria exists some degree of overlap in the findings between autoimmune pancreatitis and pancreatic cancer (indicated by the similarity in radiologic findings, elevation of IgG4, sampling errors in pancreatic biopsy, and the possibility of synchronous autoimmune pancreatitis and pancreatic cancer). Despite the generally accepted corticosteroids as the primary treatment modality in autoimmune pancreatitis, we believe that surgical resection remains necessary in a specific subgroup of patients with autoimmune pancreatitis (Fig. 4, Ref. 37).
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Enfermedades Autoinmunes/diagnóstico , Inmunoglobulina G/sangre , Ictericia Obstructiva/etiología , Páncreas/diagnóstico por imagen , Pancreatitis/diagnóstico , Corticoesteroides , Anciano , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Diagnóstico Diferencial , Humanos , Masculino , Páncreas/patología , Neoplasias Pancreáticas , Pancreatitis/inmunología , Pancreatitis/patología , Resultado del TratamientoRESUMEN
PURPOSE: Wilms tumor gene 1 (WT1), a zinc-finger transcription factor essential for testis development and function, along with other genes, was investigated for their role in the pathogenesis of testicular germ cell tumors (TGCT). METHODS: In total, 284 TGCT and 100 control samples were investigated, including qPCR for WT1 expression and BRAF mutation, p53 immunohistochemistry detection, and massively parallel amplicon sequencing. RESULTS: WT1 was significantly (p < 0.0001) under-expressed in TGCT, with an increased ratio of exon 5-lacking isoforms, reaching low levels in chemo-naïve relapsed TGCT patients vs. high levels in chemotherapy-pretreated relapsed patients. BRAF V600E mutation was identified in 1% of patients only. p53 protein was lowly expressed in TGCT metastases compared to the matched primary tumors. Of 9 selected TGCT-linked genes, RAS/BRAF and WT1 mutations were frequent while significant TP53 and KIT variants were not detected (p = 0.0003). CONCLUSIONS: WT1 has been identified as a novel factor involved in TGCT pathogenesis, with a potential prognostic impact. Distinct biologic nature of the two types of relapses occurring in TGCT has been demonstrated. Differential mutation rate of the key TGCT-related genes has been documented.
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Biomarcadores de Tumor/genética , Genes ras , Mutación , Neoplasias de Células Germinales y Embrionarias/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-kit/genética , Neoplasias Testiculares/genética , Proteína p53 Supresora de Tumor/genética , Proteínas WT1/genética , Línea Celular Tumoral , Análisis Mutacional de ADN/métodos , Regulación hacia Abajo , Estudios de Factibilidad , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Masculino , Neoplasias de Células Germinales y Embrionarias/enzimología , Neoplasias de Células Germinales y Embrionarias/patología , Fenotipo , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Neoplasias Testiculares/enzimología , Neoplasias Testiculares/patologíaRESUMEN
The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT1) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of hypoxic pulmonary hypertension in Ren-2 transgenic rats (TGR). Transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. Both TGR and HanSD rats responded to two weeks´ exposure to hypoxia with a significant increase in mean pulmonary arterial pressure (MPAP), however, the increase was much less pronounced in the former. The attenuation of hypoxic pulmonary hypertension in TGR as compared to HanSD rats was associated with inhibition of ACE gene expression and activity, inhibition of AT1receptor gene expression and suppression of ANG II levels in lung tissue. Simultaneously, there was an increase in lung ACE2 gene expression and activity and, in particular, ANG 1-7 concentrations and Mas receptor gene expression. We propose that a combination of suppression of ACE/ANG II/AT1receptor axis and activation of ACE2/ANG 1-7/Mas receptor axis of the RAS in the lung tissue is the main mechanism explaining attenuation of hypoxic pulmonary hypertension in TGR as compared with HanSD rats.
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Angiotensina I/metabolismo , Hipertensión Pulmonar/prevención & control , Hipoxia/complicaciones , Pulmón/enzimología , Fragmentos de Péptidos/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina , Renina/metabolismo , Angiotensina II/metabolismo , Enzima Convertidora de Angiotensina 2 , Animales , Presión Arterial , Modelos Animales de Enfermedad , Hipertensión Pulmonar/enzimología , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/fisiopatología , Hipoxia/enzimología , Hipoxia/fisiopatología , Proto-Oncogenes Mas , Ratas Sprague-Dawley , Ratas Transgénicas , Receptor de Angiotensina Tipo 1/metabolismo , Renina/genética , Transducción de Señal , Vasoconstricción , VasodilataciónRESUMEN
OBJECTIVE: Analysis of one case of vulvar extramammary Paget´s disease (EMPD) and associated well differentiated endometrial adenocarcinoma.Desing: A case report. METHODS AND RESULTS: On this case report we present current theoretical knowledge about EMPD, difficulty of diagnostics, treatment and dispensarization the patients with this rare intraepithelial non-squamous neoplasia. We report a rare case of a 62 years old female patient with extramammary Paget´s disease of vulva and associated well differentiated endometrial adenocarcinoma. CONCLUSIONS: EMPD is a rare intraephitelial non-squamous neoplasia, which represents less then 1% vulvar tumors. Predominantly it affects white women between 60 and 80 years of age. EMPD occurs in cutaneous areas bearing apocrine glands - vulva, perineum, perianal area, axilla, penis, scrotum and rarely region of tights or buttocks. It is characterized microscopically by the presence of specific tumor cells called Paget´s cells - atypical large cells with pale clear cytoplasm and large round nuclei. KEYWORDS: extramammary Paget´s disease, EMPD, Paget´s cells, vulvectomy, imiquimod 5%, photodynamic therapy, imunotherapy, radiotherapy.
RESUMEN
Acute liver failure (ALF) is a clinical condition with very high mortality rate. Its pathophysiological background is still poorly understood, which necessitates a search for optimal experimental ALF models with features resembling those of the human disorder. Taking into consideration reproducibility of induction of ALF, adequate animal size, cost of animals, the required time gap between insult and death of animals ("therapeutic window"), potential risk to investigator and other aspects, administration of thioacetamide (TAA) in rats is currently most recommended. However, the fundamental details of this ALF model have not yet been evaluated. This prompted us to investigate, first, the course of ALF as induced by intraperitoneal TAA at doses increasing from 175 to 700 mg/kg BW per day. The animals' survival rate, plasma alanine and aspartate aminotransferase activities, and bilirubin and ammonia levels were determined over the follow-up period. Second, we examined whether Wistar and Lewis rats exhibit any differences in the course of ALF induced by different TAA doses. We found that the optimal dose for ALF induction in rats is 350 mg.kg(-1) i.p., given as a single injection. Wistar rats proved more susceptible to the development of TAA-induced ALF compared with Lewis rats. Collectively, our present findings provide a sound methodological background for experimental studies aimed at evaluation of pathophysiology and development of new approaches in the therapy of ALF.
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Carcinógenos/toxicidad , Fallo Hepático Agudo/inducido químicamente , Tioacetamida/toxicidad , Animales , Carcinógenos/administración & dosificación , Relación Dosis-Respuesta a Droga , Hígado/patología , Fallo Hepático Agudo/patología , Masculino , Ratas , Ratas Endogámicas Lew , Ratas Wistar , Especificidad de la Especie , Tioacetamida/administración & dosificaciónRESUMEN
OBJECTIVE: To evaluate risk factors for development of recurrent disease in borderline ovarian tumors. DESIGN: Retrospective study of 10-years single institution population. SETTING: Dept. of Gynecology and Obstetrics, 3rd Medical Faculty of Charles University in Prague. METHOD: 59 consecutive cases of borderline ovarian tumors (BOT) were analyzed for age, histopathological type, DNA ploidy, stage, presence of invasive and non-invasive peritoneal implants, type of surgical procedure, residual disease, adjuvant therapy, recurrence and long-time prognosis of the patients. RESULTS: Median follow-up was 47 months (range 1-144). There were 5 (8.5%) patients with DNA aneuploid tumors in the study group; 4 of them were younger than 50 years, 4 of them were early stage serous BOT; no one recur so far. No death of disease was described in the whole study group; only 2 patients (3.4%) developed recurrent disease - both were young patients after conservative surgery for serous diploid stage I/II BOT. Conservative surgery was the only significant factor for recurrence in univariate analysis (p = 0.0159) in our setting. CONCLUSION: DNA ploidy was not proved to be prognostic factor in borderline ovarian tumors in our study group. The only significant risk factor for development of recurrent disease was conservative surgery, with no influence on overall survival.
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Recurrencia Local de Neoplasia , Neoplasias Ováricas/patología , Adulto , Anciano , Anciano de 80 o más Años , ADN de Neoplasias/genética , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/cirugía , Ploidias , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
OBJECTIVE: To develop guideline for primary surgical treatment of endometrial carcinoma. DESIGN: Review, consensus of expert group. SETTING: Dept. of Gynaecology and Obstetrics, 3rd Medical Faculty of Charles University in Prague. METHOD: A retrospective review of published data, analysis of statistic data from Czech Republic, consensus among proposers and opponents. RESULTS: The guideline recognizes endometrial carcinoma patients based on their risk and recommends type of surgical treatment for certain group. It emphasizes the importance of centralized oncogynaecological treatment. Surgical staging remains the basic principle for treatment of endometrial carcinoma patients. The aim of pre-operative diagnostics is to estimate the extent of the disease--"interim staging", that can be different from definitive histopathological staging. Based on risk factors patients are divided into low or high risk group. Standard procedure for low risk patients is hysterectomy and bilateral salpingoophorectomy. It is advisable to use peroperative biopsy in these patients that can shift the patient to high risk group. High risk patients are recommended for hysterectomy, bilateral salpingoophorectomy, and systematic aortopelvic lymphadenectomy. The guideline contains recommendation for young patients wishing to preserve their fertility, for cases of inadequate surgery and for follow-up. CONCLUSION: Guideline for treatment of endometrial carcinoma is recommendation for clinicians and other subjects who participate on the process of the diagnostics/treatment of endometrial carcinoma patients. All points of the guideline were discussed and voted about by all participants of expert group.
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Neoplasias Endometriales/cirugía , Protocolos Clínicos , Neoplasias Endometriales/diagnóstico , Femenino , HumanosRESUMEN
INTRODUCTION: Post-traumatic splenic pseudocysts are rare condition and comprise more than 75% of non-parasitic cysts. They result from subcapsular or intraparenchymatous hematoma, by its liquefaction and creation of the fibrous peripheral capsula. Splenic pseudocysts have no epithelial lining, its diameter could be more than 15 cm and are mostly symptomatic. CASE REPORT: A female, 53 years old, was admitted to the Clinic of surgery with blunt pains in the left hypochondrium after falling on the left side of body 6 months ago. Ultrasonography and CT scan reveal posttraumatic pseudocyst of the spleen, 156 x 135 x 148 mm in diameter. The splenic parenchyma was reduced to 15 mm dorso-caudal. Extirpation of the pseudocyst and splenectomy during laparotomy was performed with healing per primam. The patient was discharged 6 day after surgery. CONCLUSION: Posttraumatic splenic pseudocysts are good diagnosed in CT scan. Giant pseudocysts and psuedocysts in splenic hilus require surgical resection. Spleen parenchyma preserving operations, currently recommended in small cysts, reduce the risk of early and late septic complications, particularly overwhelming postsplenectomy sepsis. Partial splenectomy offers a definitive treatment of a splenic cyst while preserving splenic functions. Miniinvasive surgery as a percutaneous drainage and laparoscopic fenestration have an unacceptably high rate of failure.
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Quistes/etiología , Enfermedades del Bazo/etiología , Heridas no Penetrantes/complicaciones , Quistes/diagnóstico por imagen , Quistes/cirugía , Femenino , Humanos , Persona de Mediana Edad , Enfermedades del Bazo/diagnóstico por imagen , Enfermedades del Bazo/cirugía , Tomografía Computarizada por Rayos XAsunto(s)
ADN Viral/sangre , Herpesvirus Humano 4/genética , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/virología , Valor Predictivo de las Pruebas , Adolescente , Adulto , Anciano , Femenino , Enfermedad de Hodgkin/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Carga Viral , Adulto JovenRESUMEN
The rat strain transgenic for the murine Ren-2 renin gene (TGR) is defined as a monogenic model of angiotensin II-dependent hypertension with endogenous activation of the renin-angiotensin system. Homozygous males TGR develop malignant hypertension with a strong salt-sensitive component. These animals show severe hypertension, proteinuria and high mortality. Morphological changes of renal parenchyma correspond to chronic ischemic glomerular changes. Heterozygous TGR develop only mild hypertension and thus provide a more suitable model of hypertension regarding to clinical studies. Within the renal parenchyma, secondary focal segmental glomerulosclerosis (FSGS) predominates. High-salt diet in heterozygous animals induces transition from benign to malignant phase of hypertension. In this case, ischemic glomerular changes are superimposed on preexisting secondary FSGS. In the regression model of hypertension (late-onset treatment) the effect of salt intake is attenuated. In homozygous TGR, early selective ET(A) receptor blockade decreased blood pressure and ameliorated end-organ damage. Late selective ET(A) receptor blockade reduced podocyte injury despite final severe hypertension. Survival rate was markedly improved in both regimens with ET(A) selective blockade, while there was only partial improvement with early non-selective blockade. Both bosentan and atrasentan decreased ET-1 levels in both regimens. In heterozygous TGR, early and late ET(A) treatment substantially while ET(A)/ET(B) treatment partially improved survival rate. Significant effect on BP was found with early and late ET(A) blockade, while ET(A)/ET(B) blockade had no effect. Bosentan and atrasentan similarly decreased ET-1 levels on both regimens. In conclusion, selective ET(A) receptor blockade is superior to nonselective ET(A)/ET(B) receptor blockade in attenuating hypertension and end-organ damage. Its effect is more pronounced when applied early in the life.
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Antihipertensivos/farmacología , Antagonistas de los Receptores de la Endotelina A , Glomeruloesclerosis Focal y Segmentaria/prevención & control , Hipertensión/tratamiento farmacológico , Pirrolidinas/farmacología , Renina/genética , Sulfonamidas/farmacología , Animales , Atrasentán , Presión Sanguínea/efectos de los fármacos , Bosentán , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Antagonistas de los Receptores de la Endotelina B , Endotelina-1/metabolismo , Glomeruloesclerosis Focal y Segmentaria/genética , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Heterocigoto , Homocigoto , Hipertensión/complicaciones , Hipertensión/genética , Hipertensión/metabolismo , Hipertensión/fisiopatología , Masculino , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Podocitos/patología , Ratas , Ratas Transgénicas , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Cloruro de Sodio Dietético , Factores de TiempoRESUMEN
Resistin is a member of adipokine family involved in the regulation of inflammatory reactions and insulin sensitivity. In presented study its possible role in the development of benign prostate hyperplasia and prostate cancer was evaluated. Blood samples and prostate specimens were collected from 26 patients with benign prostate hyperplasia (BPH) and from 42 patients with prostate cancer (PCa) stage pT2 (n=18) and pT3 (n=24). Selected metabolic and biochemical parameters and serum resistin levels were measured and anthropometric measurements were performed as well as tissue immunohistochemistry for resistin. Serum resistin levels did not differ significantly between benign hyperplasia and prostate cancer but in cancer patients there was a trend towards decrease with higher cancer stage. Moreover, serum resistin levels were significantly lower in patients with seminal vesicle invasion in comparison to those without invasion. While in BPH serum resistin levels correlated with insulin resistance, inflammatory status and cortisol, in PCa positive correlation with F/T PSA ratio and cortisol was observed. Tissue immunohistochemistry did not show any differences in staining pattern between benign and neoplastic prostate tissue. We conclude that serum resistin levels do not significantly differ between patients with benign prostate hyperplasia and prostate cancer, but there is a trend towards decrease in resistin serum levels in advanced cancer cases.
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Hiperplasia Prostática/sangre , Neoplasias de la Próstata/sangre , Resistina/sangre , Anciano , Progresión de la Enfermedad , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patologíaRESUMEN
Female carriers of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency have somatic cell mosaicism of HPRT activity and are healthy. We report a 50-year-old woman without gout or nephrolithiasis. She was never on allopurinol. Normal serum uric acid concentrations, increased plasma hypoxanthine, and xanthine were found. HPRT activity in erythrocytes was surprisingly low: at 8.6 nmol h(-1) mg (-1) haemoglobin. Mutation analysis revealed a heterozygous HPRT gene mutation, c.215A > G (p.Tyr72Cys). Assessment of X-inactivation ratio has shown that > 75% of the active X-chromosome bears the mutant allele and could explain these unusual, previously undescribed findings.
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Hipoxantina Fosforribosiltransferasa/deficiencia , Síndrome de Lesch-Nyhan/enzimología , Síndrome de Lesch-Nyhan/genética , Adulto , Alelos , Femenino , Heterocigoto , Humanos , Hipoxantina Fosforribosiltransferasa/genética , Hipoxantina Fosforribosiltransferasa/metabolismo , Síndrome de Lesch-Nyhan/metabolismo , Síndrome de Lesch-Nyhan/patología , Masculino , Persona de Mediana Edad , Mutación , Linaje , Purinas/sangre , Síndrome , Inactivación del Cromosoma XRESUMEN
Serum levels of adiponectin were measured in patients with benign prostatic hyperplasia and prostate cancer of pT2 and pT3 stage. Adiponectin ELISA assay, immunohistochemistry, and selected metabolic and biochemical parameters measurement was performed in 25 patients with benign prostatic hyperplasia and 43 with prostate cancer (17 patients with organ-confined and 26 patients with locally advanced disease). Serum adiponectin levels did not differ between prostate benign hyperplasia and cancer clinical stage T2, but was significantly higher in pT3 relative to pT2 group (14.51+/-4.92 vs. 21.41+/-8.12, P = 0.003). Tissue immunohistochemistry showed enhanced staining in neoplastic prostate glands and intraepithelial neoplasia relative to benign prostatic hyperplasia without distinction between disease grade and stage. Serum adiponectin levels are higher in locally advanced relative to organ-confined prostate cancer and may thus serve as an auxiliary marker providing further improvement for discrimination between pT2 and pT3 stages.
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Biomarcadores de Tumor/sangre , Hiperplasia Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Adiponectina/sangre , Anciano , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Prostatectomía , Hiperplasia Prostática/patología , Hiperplasia Prostática/cirugía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugíaRESUMEN
Experimental model of 5/6 nephrectomy or the remnant kidney model represents one of the most used animal models of progressive renal failure by reduced nephron number, best-characterized in rats. The reduction of renal mass is achieved by either infarction or surgical excision of both poles, with removal of the contralateral kidney. It enables to investigate the influence of pharmacological, nutritive and other factors on functional and morphological renal parameters. 5/6 nephrectomy produced by infarction is characterised by high plasma renin levels. By contrast, reduction of an equivalent amount of renal parenchyma by surgical excision does not result in the development of hypertension and plasma renin activity is normal to low. The initially normal remnant nephrons undergo compensatory functional and structural adaptations. Simultaneous glomerular hypertension is one of the main factors responsible for the development of renal injury. Morphologicaly progressive focal segmental to global glomerulosclerosis is present, accompanied clinically by increasing proteinuria and deteriorating renal function.
Asunto(s)
Modelos Animales de Enfermedad , Fallo Renal Crónico/fisiopatología , Nefrectomía/métodos , Nefronas/fisiopatología , Adaptación Fisiológica , Animales , Progresión de la Enfermedad , Tasa de Filtración Glomerular , Riñón/patología , Fallo Renal Crónico/patología , Proteinuria , Circulación RenalRESUMEN
BACKGROUND: Resistin is a newly identified adipocytokine which has demonstrated links between obesity and insulin resistance in rodents. In humans, proinflammatory properties of resistin are superior to its insulin resistance-inducing effects. OBJECTIVES: To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis and spondylarthropathies (SpA), and to study its relationship with inflammatory status and rheumatoid arthritis disease activity. METHODS: Resistin expression and localisation in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin (IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant protein-1 levels were measured. The clinical activity of patients with rheumatoid arthritis was assessed according to the 28 joint count Disease Activity Score (DAS28). RESULTS: Resistin was detected in the synovium in both rheumatoid arthritis and osteoarthritis. Staining in the sublining layer was more intensive in patients with rheumatoid arthritis compared with those with osteoarthritis. In rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial fluid resistin was higher in patients with rheumatoid arthritis than in those with SpA or osteoarthritis (both p<0.001). In patients with rheumatoid arthritis and SpA, serum resistin levels were higher than those with osteoarthritis (p<0.01). Increased serum resistin in patients with rheumatoid arthritis correlated with both CRP (r=0.53, p<0.02), and DAS28 (r=0.44, p<0.05), but not with selected (adipo) cytokines. CONCLUSION: The upregulated resistin at local sites of inflammation and the link between serum resistin, inflammation and disease activity suggest a role for resistin in the pathogenesis of rheumatoid arthritis.
Asunto(s)
Artritis Reumatoide/metabolismo , Resistina/análisis , Membrana Sinovial/química , Adulto , Anciano , Artritis Reumatoide/sangre , Biomarcadores/sangre , Femenino , Humanos , Técnicas para Inmunoenzimas , Mediadores de Inflamación/análisis , Masculino , Microscopía Confocal , Persona de Mediana Edad , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Rodilla/metabolismo , Resistina/sangre , Índice de Severidad de la Enfermedad , Espondiloartropatías/sangre , Espondiloartropatías/metabolismo , Líquido Sinovial/químicaRESUMEN
BACKGROUND: AA amyloidosis caused by the chronic inflammation accompanying gouty arthritis is extremely rare and familial occurrence has not been described so far. CASE REPORT: We present the case of two brothers (47 and 44 years old) with 7- and 10-year history of hyperuricaemia and chronic tophaceous gout with polyarticular involvement. The enzymatic assay performed in their erythrocytes proved the partial hypoxanthine-guanine phosphoribosyl transferase deficiency (Kelley-Seegmiller syndrome), the genetic defect of purine metabolism. Later on they developed proteinuria and chronic renal insufficiency /CRI/. Renal biopsy disclosed the combination of AA amyloidosis and gouty nephropathy in both the cases. Despite the standard treatment the older brother progressed to chronic renal failure. On the contrary, the younger one being longterm treated with oral colchicin have stabilized CRI. CONCLUSIONS: Only several cases of AA renal amyloidosis until recently, secondary to gout have been reported. Our case represents the first report of familial occurrence of this extremely rare disease.