Heberprot-P's Effect on Gene Expression in Healing Diabetic Foot Ulcers.

NTRODUCTION Diabetic foot ulcers are a chronic complication in patients with diabetes mellitus. They appear as a result of the combination of diabetic polyneuropathy and angiopathy, and in many cases require amputation of the affected extremity. Clinical trials have demonstrated that repeated local infiltration with Heberprot-P can improve healing of chronic diabetic foot ulcers. Although there is evidence of its effects as a granulation stimulator and on cell migration and proliferation, genetic control mechanisms explaining its anti-inflammatory and oxidative stress reduction properties are not yet thoroughly understood. OBJECTIVE Analyze changes in expression of genes involved in healing after treatment of diabetic foot ulcers with Heberprot-P. METHODS Biopsies were collected from diabetic foot ulcers of 10 responding patients before and after 2 weeks' treatment with Heberprot-P (75-µg applied intralesionally 3 times per week). Total RNA was obtained and quantitative PCR used to determine expression of 26 genes related to inflammation, oxidative stress, cell proliferation, ngiogenesis and extracellular matrix formation. Genetic expression was quantified before and after treatment using REST 2009 v2.0.13. RESULTS After treatment, there was a statistically significant increase in expression of genes related to cell proliferation, angiogenesis and formation of extracellular matrix (PDGFB, CDK4, P21, TP53, ANGPT1, COL1A1, MMP2 and TIMP2). A significant decrease was observed in gene expression related to inflammatory processes and oxidative stress (NFKB1, TNFA and IL-1A). CONCLUSIONS Our findings suggest that Heberprot-P's healing action on diabetic foot ulcers is mediated through changes in genetic expression that reduce hypoxia, inflammation and oxidative stress, and at the same time increase cell proliferation, collagen synthesis and extracellular matrix remodeling. The kinetics of expression of two genes related to extracellular matrix formation needs further exploration. KEYWORDS Epidermal growth factor, EGF, diabetic foot ulcer, wound healing, quantitative real-time PCR, gene expression, Cuba.

Expression Changes in Metal-Resistance Genes in Microbacterium liquefaciens Under Nickel and Vanadium Exposure.

Microbacterium liquefaciens MNSH2-PHGII-2 is a nickel-vanadium-resistant bacterium isolated from mine tailings located in Guanajuato, Mexico. In PHGII liquid media, M. liquefaciens has the ability to remove 29.5 ppm of Ni and 168.3 ppm of V. The present study reports, for the first time in M. liquefaciens, the presence of the genes nccA (Ni-Co-Cd resistance), hant (high-affinity nickel transporter), smtA, a metal-binding protein gene, and VAN2 (V resistance), which showed an increased expression under exposure to 200 ppm of Ni and 200 ppm of V during the logarithmic growth phase of the microorganism in PHGII liquid media. Data about the expression profile of genes conferring metal resistance to M. liquefaciens can improve the knowledge of those mechanisms involved in the processes of Ni-V resistance and probably in Ni-V removal processes. Based on our data, we can suggest that M. liquefaciens has the potential to be used in the biological treatment of toxic wastes with high Ni and V content.

Propiedades inmunomoduladoras de las células madre mesenquimales / Inmunomodulatory properties of mesenchymal stem cells

Las estrategias de terapia celular se han utilizado con fines tan diversos como la regeneración de tejidos, la potenciación de la respuesta inmune antígeno específicas para la terapia antitumoral, la liberación de drogas en tejidos dañados y la restauración de la homeostasis en sitios con procesos inflamatorios crónicos. Dentro de las poblaciones celulares con mayor potencial para este tipo de alternativa terapéutica se incluyen las células madre mesenquimales (CMM), un grupo heterogéneo de células estromales multipotentes que se caracterizan por su baja inmunogenicidad y que ha demostrado una elevada versatilidad respecto a sus efectos inmunomoduladores. El presente trabajo recoge evidencias que se han acumulado en la última década que permiten valorar el potencial de las CMM para la terapia celular(AU)

Cellular therapy is a versatile therapeutic approach that has been assessed on tissue regeneration, on the enhancement of tumor specific immune response, on the delivery of drugs to damage tissues and on the restoring of tissue homeostasis at chronic inflamed sites. Among the cell populations used for cellular therapy, multipotent mesenchymal stem cells (MSC) appear as a heterogeneous group of cells with the highest potentiality based on its low immunogenicity and its ability to exert a plethora of immunomodulatory effects. This paper reviews the experimental evidences accumulated during the last decade in order to estimate the relevance of MSC for therapies based on cellular transference(AU)

Effectiveness of hexaminolevulinate fluorescence cystoscopy for the diagnosis of non-muscle-invasive bladder cancer in daily clinical practice: a Spanish multicentre observational study.

OBJECTIVE: To assess the sensitivity and specificity of blue-light cystoscopy (BLC) with hexaminolevulinate as an adjunct to white-light cystoscopy (WLC) vs WLC alone for the detection of non-muscle-invasive bladder cancer (NMIBC), in routine clinical practice in Spain. PATIENTS AND METHOD: An intra-patient comparative, multicentre, prospective, observational study. Adults with suspected or documented primary or recurrent NMIBC at eight Spanish centres were included in the study. All patients were examined with WLC followed by BLC with hexaminolevulinate. We evaluated the detection rate of bladder cancer lesions by WLC and BLC with hexaminolevulinate, overall and by tumour stage and compared with histological examination of the biopsied lesions. Sensitivity and specificity was calculated. RESULTS: In all, 1,569 lesions were identified from 283 patients: 621 were tumour lesions according to histology and 948 were false-positives. Of the 621 tumour lesions, 475 were detected by WLC (sensitivity 76.5%, 95% confidence interval [CI] 73.2-79.8) and 579 were detected by BLC (sensitivity 93.2%, 95% CI 91.0-95.1; P < 0.001). There was a significant improvement in the sensitivity in the detection of all types of NMIBC lesions with BLC compared with WLC. Of 219 patients with tumours, 188 had NMIBC [highest grade: carcinoma in situ (CIS), n = 36; Ta, n = 87; T1, n = 65). CIS lesions were identified more with BLC (n = 27) than with WLC [n = 19; sensitivity: BLC 75.0% (95% CI 57.8-87.9) vs WLC 52.8% (95% CI 35.5-69.6); P = 0.021]. Results varied across centres. CONCLUSIONS: This study shows that improvement in diagnosis of NMIBC, mainly CIS and Ta tumours, obtained with BLC with hexaminolevulinate as an adjunct to WLC vs WLC alone can be shown in routine clinical practice.

Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction).

OBJECTIVES: The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. BACKGROUND: Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). METHODS: The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. RESULTS: Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). CONCLUSIONS: In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial; NCT01311700).

Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial.

BACKGROUND: The effect of ß-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously before reperfusion). METHODS AND RESULTS: Patients with Killip class II or less anterior ST-segment-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean ± SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6 ± 15.3 versus 32.0 ± 22.2 g; adjusted difference, -6.52; 95% confidence interval, -11.39 to -1.78; P=0.012). In patients with pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was -8.13 (95% confidence interval, -13.10 to -3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09-5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21). CONCLUSIONS: In patients with anterior Killip class II or less ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01311700. EUDRACT number: 2010-019939-35.

Cardiac anatomy for the interventional arrhythmologist: I.terminology and fluoroscopic projections.

Cardiac anatomy is complex and its understanding is essential for the interventional arrhythmologist. The first difficulty is the terminology used to describe the location of sites of mapping and ablation. For many years, electrophysiologists have named these positions following the conventional electrocardiographical vocabulary, or the terminology used by surgeons performing arrhythmic surgery. This traditional nomenclature, however, failed to take note of the crucial principle of considering the location of the heart in the human body as viewed in its erect position. In other words, it had failed to use an attitudinally appropriate terminology. Almost 10 years ago, a new attitudinal nomenclature was proposed for the right and left atrioventricular junctions. In this first of a series of reviews of cardiac anatomy as seen by the interventional arrhythmologist, we discuss the role of attitudinally appropriate terminology, and relate this to the projections used for cardiac fluoroscopy, fluorography, and angiography. Throughout our series of reviews, we will illustrate the value of The Visible Human Slice and Surface Server in facilitating the understanding of the fluoroscopic anatomy. (PACE 2010; 497-507).

Thyroid implants after surgery and blunt trauma.

The differential diagnosis of thyroid tissue found laterally in the neck includes several conditions: lymph node deposits of thyroid carcinoma, "benign metastatic thyroidosis," detached thyroid nodules, and true ectopic thyroid tissue. We have studied nine cases with thyroid deposits in the soft tissues of the neck that do not conform to these diagnoses. We present evidence that they represent surgical or traumatic implantation of thyroid neoplasms. Eight of the nine cases presented one to 26 years after initial surgery. Adequate information of the operative procedure was available in seven cases, one patient underwent subtotal lobectomy and six subtotal thyroidectomy for a nodular gland. The nodules occurred within the operation field with no evidence that they were within lymph nodes. In six cases, birefringent particles consistent with talc from the earlier operation were found adjacent to the nodules. Three cases showed implants of colloid nodules, three of follicular adenoma, one of oncocytic (Hürthle) cell adenoma and one of follicular carcinoma. In the ninth case, infiltrating thyroid tissue in muscle and fibrous tissue presented 3 years after major blunt trauma to the neck. The tissue resembled that in a disrupted thyroid nodule present in the gland itself and was regarded as traumatically implanted. The observation that surgery or trauma to a nodular thyroid can occasionally lead to multiple subcutaneous thyroid implants has implication for management of thyroid disease. Therapy may be difficult; recurrence followed surgical removal of the nodules in three cases, and radioiodine may be a more effective therapy. Recognition of this entity is important for accurate pathologic diagnosis. It is apparently limited to implantation of tumor. The absence of implantation of normal or hyperplastic thyroid, despite the high frequency of partial thyroidectomy in Graves' disease, has pathobiological implications. These findings also support the generally held view that lobectomy rather than nodulectomy is the operation of choice for a solitary nodule.

Caracterización etiológica de las meningoencefalitis asépticas en la provincia Ciego de Avila, Cuba / Etiologic characterization of aseptic meningoencephalitis in the province of Ciego de Avila, Cuba

Se realiza análisis prospectivo aleatorio a 198 pacientes con meningoencefalitis aséptica (MEA) ingresados en el servicio de medicina del hospital provincial ®Dr. Antonio Luaces Iraola¼ de Ciego de Avila, Cuba. Se les efectuó estudios con sueros pareados para determinar anticuerpos neutralizantes a enterovirus, pruebas de hemoglutinación, neutralización viral para arbovirus, hemolítica para leptospira y estudio virológico de heces fecales buscando enterovirus. En 36.8 por ciento de los pacientes se encontró como agente etiológico un enterovirus. El segundo agente en frecuencia fue la leptospira en 14.6 por ciento. Se determinó el agente etiológico en 51.4 por ciento de los pacientes estudiados