Bone union formation in the rat mandibular symphysis using hydroxyapatite with or without simvastatin: effects on healthy, diabetic, and osteoporotic rats.

OBJECTIVE: The objective is to compare new bone formation in critical defects in healthy, diabetic, and osteoporotic rats filled with hydroxyapatite (HA) alone and HA combined with simvastatin (SV). MATERIALS AND METHODS: A total of 48 adult female Sprague-Dawley rats were randomized into three groups (n = 16 per group): Group, 1 healthy; Group 2, diabetics; and Group 3, osteoporotics. Streptozotocin was used to induce type 1 diabetes in Group 2, while bilateral ovariectomy was used to induce osteoporosis in Group 3. The central portion of the rat mandibular symphysis was used as a physiological critical bone defect. In each group, eight defects were filled with HA alone and eight with HA combined with SV. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2). RESULTS: In all groups (healthy, diabetics, and osteoporotics), the defects filled with HA + SV presented greater radiological bone union, BMD, histological bone union, and more VEGF and BMP-2 positivity, in comparison with bone defects treated with HA alone. CONCLUSIONS: Combined application of HA and SV improves bone regeneration in mandibular critical bone defects compared with application of HA alone in healthy, diabetic, and osteoporotic rats. CLINICAL RELEVANCE: This study might help to patients with osteoporosis or uncontrolled diabetes type 1, but future studies should be done.

Synergistic effect of photodynamic therapy and alendronate on alveolar bone loss in rats with ligature-induced periodontitis.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) and antiresorptive drugs, such as alendronate (ALN), have been shown to reduce alveolar bone loss. The aim of this study was to evaluate the possible synergic effects of combining PDT and ALN on bone loss in periodontitis in rats. MATERIAL AND METHODS: Periodontitis was induced by ligature in 60 Wistar rats randomized into the following groups: control (Group 1); PDT (Group 2); ALN 0.01 mg/kg (Group 3); ALN 0.25 mg/kg (Group 4); PDT + ALN 0.01 mg/kg (Group 5); and PDT + ALN 0.25 mg/kg (Group 6). The rats were killed on day 12 and the mandibles were processed for macroscopic morphometric analysis, micro-computed tomography to analyze bone mineral density (BMD) and histological analysis. Gingival samples were collected to evaluate myeloperoxidase (MPO) and malonaldehyde (MDA) levels. RESULTS: Bone loss and inflammatory activity in histological studies, from the greatest to least was: control > ALN 0.01 mg/kg > PDT > ALN 0.25 mg/kg > PDT + ALN 0.01 mg/kg > PDT + ALN 0.25 mg/kg, while the order from least to greatest BMD was: control < ALN 0.01 mg/kg < PDT < ALN 0.25 mg/kg < PDT + ALN 0.01 mg/kg < PDT + ALN 0.25 mg/kg. The order of MPO and MDA activity from greatest to least was: control > ALN 0.01 mg/kg > PDT > ALN 0.25 mg/kg > PDT + ALN 0.01 mg/kg > PDT + ALN 0.25 mg/kg. The positive results obtained in the group treated with PDT + ALN 0.25 mg/kg showed statistically significant differences (P ≤ .05) compared with the other 5 groups for BMD, MPO and MDA. CONCLUSION: Combined approach therapy of PDT + ALN 0.25 mg/kg demonstrated a protective effect on alveolar bone loss.

Initial evaluation and management of the critical burn patient / Evaluación inicial y manejo del paciente quemado crítico

The major improvement in burn therapy is likely to focus on the early management of hemodynamic and respiratory failures in combination with an aggressive and early surgical excision and skin grafting for full-thickness burns. Immediate burn care by first care providers is important and can vastly alter outcomes, and it can significantly limit burn progression and depth. The goal of prehospital care should be to cease the burning process as well as prevent future complications and secondary injuries for burn shock. Identifying burn patients appropriate for immediate or subacute transfer is an important step in reducing morbidity and mortality. Delays in transport to Burn Unit should be minimized. The emergency management follows the principles of the Advanced Trauma Life Support Guidelines for assessment and stabilization of airway, breathing, circulation, disability, exposure and environment control. All patients with suspected inhalation injury must be removed from the enclosure as soon as possible, and immediately administer high-flow oxygen. Any patient with stridor, shortness of breath, facial burns, singed nasal hairs, cough, soot in the oral cavity, and history of being in a fire in an enclosed space should be strongly considered for early intubation. Fibroscopy may also be useful if airway damage is suspected and to assess known lung damage. Secondary evaluation following admission to the Burn Unit of a burned patient suffering a severe thermal injury includes continuation of respiratory support and management and treatment of inhalation injury, fluid resuscitation and cardiovascular stabilization, pain control and management of burn wound (AU)

Los principales avances en el tratamiento de la quemadura se centran en el manejo precoz de la disfunción hemodinámica y respiratoria junto con la excisión quirúrgica agresiva y precoz y el injerto de piel en quemaduras de espesor total. La atención inmediata a la quemadura puede cambiar el pronóstico, limitando significativamente su progresión y profundidad. El objetivo de la asistencia prehospitalaria es detener el proceso de combustión así como prevenir posteriores complicaciones y daños secundarios al shock por quemadura. Identificar los pacientes quemados subsidiarios de traslado inmediato es importante en términos de morbilidad y mortalidad. La demora en el traslado a una Unidad de Quemados de referencia debe ser minimizada. El manejo emergente debe ser el mismo que para cualquier otro paciente politraumatizado, con evaluación y estabilización de la vía aérea, la respiración, la circulación, la discapacidad y el control ambiental. Todos los pacientes con sospecha de inhalación deben ser trasladados del recinto tan pronto como sea posible y administrar inmediatamente oxígeno a alto flujo. Ante un paciente con estridor, dificultad para respirar, quemaduras faciales, vibrisas quemadas, tos, hollín en la cavidad oral e historia de inhalación de humo en un lugar cerrado debe ser considerada la indicación de intubación precoz. La fibroscopia puede ser útil si se sospecha daño de la vía aérea y para evaluar el daño pulmonar conocido. La valoración secundaria tras el ingreso en la Unidad de un paciente que ha sufrido una lesión térmica grave incluye la continuación del soporte respiratorio y el manejo y tratamiento del daño por inhalación, la reanimación con líquidos y la estabilización cardiovascular, el control del dolor y el manejo de la herida (AU)

Initial evaluation and management of the critical burn patient.

The major improvement in burn therapy is likely to focus on the early management of hemodynamic and respiratory failures in combination with an aggressive and early surgical excision and skin grafting for full-thickness burns. Immediate burn care by first care providers is important and can vastly alter outcomes, and it can significantly limit burn progression and depth. The goal of prehospital care should be to cease the burning process as well as prevent future complications and secondary injuries for burn shock. Identifying burn patients appropriate for immediate or subacute transfer is an important step in reducing morbidity and mortality. Delays in transport to Burn Unit should be minimized. The emergency management follows the principles of the Advanced Trauma Life Support Guidelines for assessment and stabilization of airway, breathing, circulation, disability, exposure and environment control. All patients with suspected inhalation injury must be removed from the enclosure as soon as possible, and immediately administer high-flow oxygen. Any patient with stridor, shortness of breath, facial burns, singed nasal hairs, cough, soot in the oral cavity, and history of being in a fire in an enclosed space should be strongly considered for early intubation. Fibroscopy may also be useful if airway damage is suspected and to assess known lung damage. Secondary evaluation following admission to the Burn Unit of a burned patient suffering a severe thermal injury includes continuation of respiratory support and management and treatment of inhalation injury, fluid resuscitation and cardiovascular stabilization, pain control and management of burn wound.

[Total intravenous anesthesia for repositioning an implantable defibrillator in a patient with long QT syndrome]. / Anestesia total intravenosa para recolocación de un desfibrilador automático implantable en paciente con síndrome de QT-largo.

We report the case of a 27-year-old woman with congenital long QT syndrome (LQTS) who was scheduled for surgery to reposition an implantable defibrillator. Given the risk of sudden death due to fatal ventricular arrhythmia, the woman required implantation of a defibrillator with pacemaker capability. Combined anesthesia-analgesia was used in order to minimize the risk of ventricular arrhythmia caused by increased serum concentrations of catecholamines. When cardioversion, defibrillation and anti-tachycardia functions had been deactivated, anesthesia was induced with propofol, fentanyl and rocuronium. Anesthesia was maintained with an infusion of propofol and remifentanil. We describe the pathophysiology and treatment of LQTS and discuss anesthetic management for repositioning a defibrillator in a patient with congenital LQTS.

Anestesia total intravenosa para recolocación de un desfibriladorautomático implantable en paciente con síndrome de QT-largo / Total intravenous anesthesia for repositioning an implantable defibrillator in a patient with long QT syndrome

Presentamos el caso de una mujer de 27 años, con síndromede QT-largo (SQTL) de origen congénito, programadapara recolocación de un desfibrilador automáticoimplantable (DAI). Debido al riesgo de muerte súbitasecundario a arritmias ventriculares letales, precisó laimplantación de un DAI con capacidad de marcapasos.Para minimizar el riesgo de arritmias ventricularessecundarias al incremento de las concentraciones séricasde catecolaminas, la técnica anestésica elegida se basó enla analgesia. Desactivadas las funciones de cardioversión,desfibrilación y antitaquiarritmias, se procedió a lainducción anestésica con propofol, fentanilo y rocuronio.El mantenimiento anestésico se realizó con perfusión depropofol y remifentanilo. Describimos la fisiopatología yel tratamiento del SQTL, y se discute el manejo anestésicopara la recolocación de un DAI en una pacienteafecta de SQTL de origen congénito (AU)

We report the case of a 27-year-old woman withcongenital long QT syndrome (LQTS) who was scheduledfor surgery to reposition an implantable defibrillator.Given the risk of sudden death due to fatal ventriculararrhythmia, the woman required implantation of adefibrillator with pacemaker capability. Combinedanesthesia-analgesia was used in order to minimize therisk of ventricular arrhythmia caused by increased serumconcentrations of catecholamines. When cardioversion,defibrillation and anti-tachycardia functions had beendeactivated, anesthesia was induced with propofol,fentanyl and rocuronium. Anesthesia was maintainedwith an infusion of propofol and remifentanil. Wedescribe the pathophysiology and treatment of LQTS anddiscuss anesthetic management for repositioning adefibrillator in a patient with congenital LQTS (AU)

p21(Waf1/Cip1/Sdi1) mediates retinoblastoma protein degradation.

Damage-induced G1 checkpoint in mammalian cells involves upregulation of p53, which activates transcription of p21(Waf1) (CDKN1A). Inhibition of cyclin-dependent kinase (CDK)2 and CDK4/6 by p21 leads to dephosphorylation and activation of Rb. We now show that ectopic p21 expression in human HT1080 fibrosarcoma cells causes not only dephosphorylation but also depletion of Rb; this effect was p53-independent and susceptible to a proteasome inhibitor. CDK inhibitor p27 (CDKN1B) also caused Rb dephosphorylation and depletion, but another CDK inhibitor p16 (CDKN2A) induced only dephosphorylation but not depletion of Rb. Rb depletion was observed in both HT1080 and HCT116 colon carcinoma cells, where p21 was induced by DNA-damaging agents. Rb depletion after DNA damage did not occur in the absence of p21, and it was reduced when p21 induction was inhibited by p21-targeting short hairpin RNA or by a transdominant inhibitor of p53. These results indicate that p21 both activates Rb through dephosphorylation and inactivates it through degradation, suggesting negative feedback regulation of damage-induced cell-cycle checkpoint arrest.

Pharmacological induction of Hsp70 protects apoptosis-prone cells from doxorubicin: comparison with caspase-inhibitor- and cycle-arrest-mediated cytoprotection.

Selective modulation of cell death is important for rational chemotherapy. By depleting Hsp90-client oncoproteins, geldanamycin (GA) and 17-allylamino-17-demethoxy-GA (17-AAG) (heat-shock protein-90-active drugs) render certain oncoprotein-addictive cancer cells sensitive to chemotherapy. Here we investigated effects of GA and 17-AAG in apoptosis-prone cells such as HL60 and U937. In these cells, doxorubicin (DOX) caused rapid apoptosis, whereas GA-induced heat-shock protein-70 (Hsp70) (a potent inhibitor of apoptosis) and G1 arrest without significant apoptosis. GA blocked caspase activation and apoptosis and delayed cell death caused by DOX. Inhibitors of translation and transcription and siRNA Hsp70 abrogated cytoprotective effects of GA. Also GA failed to protect HL60 cells from cytotoxicity of actinomycin D and flavopiridol (FL), inhibitors of transcription. We next compared cytoprotection by GA-induced Hsp70, caspase inhibitors (Z-VAD-fmk) and cell-cycle arrest. Whereas cell-cycle arrest protected HL60 cells from paclitaxel (PTX) but not from FL and DOX, Z-VAD-fmk prevented FL-induced apoptosis but was less effective against DOX and PTX. Thus, by inducing Hsp70, GA protected apoptosis-prone cells in unique and cell-type selective manner. Since GA does not protect apoptosis-reluctant cancer cells, we envision a therapeutic strategy to decrease side effects of chemotherapy without affecting its therapeutic efficacy.

Cell cycle checkpoint status in human malignant mesothelioma cell lines: response to gamma radiation.

Knowledge of the function of the cell cycle checkpoints in tumour cells may be important to develop treatment strategies for human cancers. The protein p53 is an important factor that regulates cell cycle progression and apoptosis in response to drugs. In human malignant mesothelioma, p53 is generally not mutated, but may be inactivated by SV40 early region T antigen (SV40 Tag). However, the function of p53 has not been investigated in mesothelioma cells. Here, we investigated the function of the cell cycle checkpoints in six human mesothelioma cell lines (HMCLs) by studying the cell distribution in the different phases of the cell cycle by flow cytometry, and expression of cell cycle proteins, p53, p21(WAF1/CIP1) and p27(KIP1). In addition, we studied p53 gene mutations and expression of SV40 Tag. After exposure to gamma-radiation, HMCLs were arrested either in one or both phases of the cell cycle, demonstrating a heterogeneity in cell cycle control. G1 arrest was p21(WAF1/CIP1)- and p53-dependent. Lack of arrest in G1 was not related to p53 mutation or binding to SV40 Tag, except in one HMCL presenting a missense mutation at codon 248. These results may help us to understand mesothelioma and develop new treatments.

Concurrent herpes simplex type 1 and varicella-zoster in the V2 dermatome in an immunocompetent patient.

A unique feature of herpesviruses is their ability to establish latent infection within the nervous system by colonizing peripheral sensory ganglia, which results in subsequent episodic outbreaks of infection triggered by precipitating events. Despite the latent nature of both herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) within these sensory ganglia, simultaneous outbreaks of these viruses are uncommon. This is generally attributed to the differing reactivation features of these 2 viruses. Four cases of concurrent HSV-1 and VZV infection are described in the literature. We report concurrent infection of HSV-1 and VZV within the same V2 dermatome in an immunocompetent patient.

Control of cell cycle progression in human mesothelioma cells treated with gamma interferon.

Recombinant human interferon gamma (r-hu-IFNgamma) exerts both antitumoral activity in the early stages of human malignant mesothelioma and a cytostatic effect in human mesothelioma (HM) cell lines in vitro. The antiproliferative effect of interferons (IFNs) reported in a variety of cells has been attributed to several mechanisms. In order to progress in the understanding of HM cell growth modulation by r-hu-IFNgamma, modifications of cell cycle progression and expression of key cell cycle regulator proteins in response to r-hu-IFNgamma were examined. Nine HM cell lines were studied, including one resistant to the antiproliferative effect of r-hu-IFNgamma. Except in the resistant cell line r-hu-IFNgamma produced an arrest in the G1 and G2-M phases of the cell cycle, associated with a reduction in both cyclin A and cyclin dependent kinase inhibitors (CDKIs) expression. Moreover cyclin B1/cdc2 activity was decreased. The present study provides the first evidence of a G2-arrest in r-hu-IFNgamma-treated HM cell lines and indicates that HM cell lines, despite their tumorigenic origin still support cell cycle control. The cell cycle arrest induced by r-hu-IFNgamma seems to depend on cyclin regulation through p21(WAF1/CIP1)- and p27(Kip1)-independent mechanisms and is not directly related to the induced DNA damage.

Absence of SV40 large T-antigen expression in human mesothelioma cell lines.

Simian virus (SV) 40 and SV40-like DNA sequences have recently been detected in several types of human tumors, including malignant mesothelioma. However, the presence of SV40 DNA sequences is not sufficient to account for its possible role in tumor development because the viral proteins must be expressed and ultimately impair the function of relevant cell proteins, such as p53 and pRb. In this study we investigated SV40 large T antigen (SV40 Tag) protein expression in mesothelioma cell lines, established in our laboratory, by Western blotting, immunoprecipitation, and immunocytochemistry using Tag-specific mouse monoclonal antibodies (mAbs) Ab-1 (or Pab 419). By Western blotting of cell extracts, none of the mesothelioma cell lines expressed detectable amounts of SV40 Tag. However, we found that Ab-1 as well as Pab-101, another SV 40 Tag-specific mAb, may generate false-positive signals due to the fact that both antibody preparations are contaminated by a protein of similar size (90 kD) as SV40 Tag and react with the various secondary horseradish peroxidase- conjugated antimouse immunoglobulin Gs tested. The present study suggests that immunodetection of SV40 Tag protein may be puzzling because this contaminating Taglike protein may bind to particular cell structures, thereby generating false-positive signals.

Human malignant mesothelioma cell growth: activation of janus kinase 2 and signal transducer and activator of transcription 1alpha for inhibition by interferon-gamma.

Intrapleural injections of recombinant human IFN-gamma have shown some efficacy in reducing tumor growth in early stages of diffuse malignant mesothelioma (DMM). Here, we have addressed the potential therapeutic effect of IFN-gamma in DMM by investigating the activation of the JAK/STAT signaling pathway in seven human mesothelioma cell lines (HMCLs) that were differentially responsive to the antiproliferative activity of IFN-gamma. We showed that janus kinase 2 (JAK2) and signal transducer and activator of transcription 1 (STAT1) were phosphorylated on tyrosine residues within 15 min in all the HMCLs in which IFN-gamma (500 units/ml) inhibited proliferation. In addition, STAT1 binding activity to the gamma-activated sites DNA sequence was detected within 15 min in electrophoretic mobility-shift assay analysis, and IFN regulatory factor-1 RNA expression was observed within 6 h in the more responsive cells (72.7-95.2% inhibition of DNA synthesis after 72 h of treatment). Conversely, in several HMCLs, absent or limited growth suppressive effect (less than 22% inhibition of DNA synthesis) was associated with alterations in expression or activation of JAK2 or STAT1 or, downstream, with low induction of IFN regulatory factor-1 RNA expression and/or STAT1 protein expression following IFN-gamma treatment. These data suggest that at least part of the IFN-gamma effect on proliferation of HMCLs is mediated directly through activation of the JAK/STAT1 signaling pathway, and it could account for the antitumoral activity reported in DMM patients treated with IFN-gamma.

Analysis of cell cycle disruptions in cultures of rat pleural mesothelial cells exposed to asbestos fibers.

The control of DNA integrity in mammalian cells is important to maintain the cell homeostasis and prevent neoplastic transformation. Control of cell division and cell death permits repair or elimination of damaged cells. Since asbestos fibers can produce DNA damage, chromosome alterations and apoptosis in several sorts of cells, including mesothelial cells, it was interesting to investigate cell cycle disturbances in rat pleural mesothelial cells (RPMC) treated with asbestos fibers. Cell cycle analyses were performed in RPMC exposed to crocidolite (10 and 20 microg/cm2) and chrysotile (5 and 10 microg/cm2) for different times (4 to 48 h). Both fiber types entailed a G2/M accumulation in agreement with a delay in the mitosis course. Chrysotile fibers produced a G0/G1 accumulation associated with a time-dependent p53 and p21 expression. Crocidolite exposure resulted in a delay in the G1/S transition paralleling a low rate of p53 expression. These results are in agreement with a DNA damaging potential of asbestos fibers since similar results were found following RPMC exposure to gamma rays. In asbestos-treated RPMC, a low rate of apoptosis was found suggesting that RPMC may follow a DNA repair pathway that could contribute to the formation of DNA lesions. In addition, the cell cycle disturbances at the G2/M checkpoint suggest that genetically altered cells have progressed through the cycle and support the already published findings on the ability of asbestos fibers to impair cell division.

[Health education in school]. / La educación sanitaria en la escuela.

OBJECTIVES: To discover the contents of health education taught at present in the EGB (basic) schools of Castelldefels, the opinions of teachers on health education in schools, and to stimulate reflection among teachers and health-workers on health education at school. DESIGN: A crossover study using a self-administered questionnaire. SETTING: EGB schools in the town of Castelldefels. PARTICIPANTS: All the EGB teachers in Castelldefels (n = 261). MEASUREMENTS AND MAIN RESULTS: 148 teachers (57%) replied to the survey. Health education was considered necessary by 56.8% and essential by 33.1%. They needed technical support and adequate material to carry it through. Integration of health education into the teaching programmes of the school syllabus's different subjects was the best way of carrying it out, in the view of the majority. The advantage of different subjects coincided with those described in the "Health Plan for Catalonia". CONCLUSIONS: Given that we consider teachers to be the professionals best-placed to carry out health education at school, it is useful to confirm their awareness of its importance. As health education is also an objective of the primary care teams, these should be the reference and support point for teachers' demands for technical help.

[Femoral hernia in children]. / Hernia femoral en el niño.

Femoral hernia is rare in adults and even less common in children, to the point that expert surgeons have limited experience with it. Eleven patients with femoral hernia have been operated upon in our service during the past 15 years. Preoperative diagnosis was made in 6 cases (54.5%), and we underline that the ideal therapy began with this early diagnosis. We review the etiologies, clinical findings and treatment of femoral hernia in children.

Minimum-order Wiener modelling of spike-output systems.

Systems that generate spike outputs in response to continuous inputs abound in neurophysiology. The study of their dynamics with the use of systems analysis methods has been complicated by the difference in modality of the input and output signals. When the problem is placed in the framework of Wiener's theory in discrete time, an infinite functional series is required for the formal representation of the input-output relation. This has given rise to the belief that a large number of Wiener functionals is needed in practice before a model of reasonable accuracy can be obtained. In this paper, we introduce the concept of minimum-order Wiener models for spike-output systems, and we show that a low-order Wiener model is adequate in many cases for predicting fully the timing of the output spikes.