CREB decreases astrocytic excitability by modifying subcellular calcium fluxes via the sigma-1 receptor.

Astrocytic excitability relies on cytosolic calcium increases as a key mechanism, whereby astrocytes contribute to synaptic transmission and hence learning and memory. While it is a cornerstone of neurosciences that experiences are remembered, because transmitters activate gene expression in neurons, long-term adaptive astrocyte plasticity has not been described. Here, we investigated whether the transcription factor CREB mediates adaptive plasticity-like phenomena in astrocytes. We found that activation of CREB-dependent transcription reduced the calcium responses induced by ATP, noradrenaline, or endothelin-1. As to the mechanism, expression of VP16-CREB, a constitutively active CREB mutant, had no effect on basal cytosolic calcium levels, extracellular calcium entry, or calcium mobilization from lysosomal-related acidic stores. Rather, VP16-CREB upregulated sigma-1 receptor expression thereby increasing the release of calcium from the endoplasmic reticulum and its uptake by mitochondria. Sigma-1 receptor was also upregulated in vivo upon VP16-CREB expression in astrocytes. We conclude that CREB decreases astrocyte responsiveness by increasing calcium signalling at the endoplasmic reticulum-mitochondria interface, which might be an astrocyte-based form of long-term depression.

Treatment of primary spontaneous pneumothorax by videothoracoscopic talc pleurodesis under local anesthesia: a review of 133 procedures.

AIM: To review our experience of treatment of primary spontaneous pneumothorax by videothoracoscopic talc pleurodesis. METHODS: From 2000 to 2008, 124 consecutive patients with primary spontaneous pneumothorax were operated; 105 were men (84.7%) and 19 were women (15.3%) with a mean age of 26.6 years (range 17-46 years). RESULTS: No mortality was recorded. Staging according to Vanderschueren's classification was as follows: stage I, 61 patients (45.9%); stage II, 39 patients (29.3%); stage III, 31 patients (23.3%); stage IV, two patients (1.5%). The overall rate of complications was 9% (12/133), corresponding to prolonged air leak in 9(6.7%) patients and hemothorax in 3(2.2%) patients. Four patients (3%) had recurrence requiring reoperation. There were no episodes of acute respiratory failure, pneumonia or subcutaneous emphysema following talc pleurodesis. CONCLUSIONS: Thoracoscopic pleural talc pleurodesis as a treatment for recurrent pneumothorax is easy, safe, and rapid, and causes minimal morbidity and mortality.

[Specialized training in anesthesiology: the opinions of supervising tutors]. / La formación especializada en Anestesiología desde la perspectiva de los tutores.

OBJECTIVE: To evaluate the common curriculum for teaching theoretical knowledge in anesthesiology in Catalonia, Spain; to assess differences between hospital teaching programs, evaluation systems, and the situation for tutors. MATERIAL AND METHODS: A 35-item questionnaire was sent to 49 accredited tutors during the 2005-2006 academic year. The questionnaire covered 1) the curriculum and training rotations, 2) teaching and research, and 3) assessment and tutorial interventions. An additional question asked the respondent's view on how to improve instruction. RESULTS: Eighty-five percent of the tutors responded. Seventy-eight percent of the residents (168/216) follow some form of external rotation, most often in pediatric anesthesia (79%). The common courses are considered useful by 96% of the tutors. Ninety-two percent are satisfied with the current annual examination and 79% would extend the residency training period to 5 years. Eighty-two percent of the teaching centers have weekly instructional sessions. Eighty-one percent of the tutors consider the resident's logbook, filled in by 77% of residents, to be useful for assessment. Eighty-five percent take teacher training courses, 65% feel that their work is being recognized, and 92% do not allot a specific period of time for teaching. CONCLUSIONS: The survey has helped shed light on the current training situation in Catalonia. The common courses are of great help. The number of external rotations is high, overloading certain areas. Improvements could be made by unifying external rotations, updating the curriculum and extending the training period to 5 years, recognizing the role of the tutor, and establishing a specific time for teaching activity.

Anatomical redistribution of sweating after T2-T3 thoracoscopic sympathicolysis: a study of 210 patients.

BACKGROUND: The cutaneous influence areas of the different sympathetic ganglia have not been fully established to date. The aim of this study was to define the cutaneous influence area of sympathetic ganglia T2-T3. METHODS: A total of 210 patients with primary hyperhidrosis (PH) underwent 420 thoracoscopic sympathicolysis procedures of ganglia T2-T3 in a prospective study. All completed a preoperative questionnaire and a second questionnaire 12 months after the operation. The questionnaires evaluated perspiration in the different body areas. Only the zones of anhidrosis were considered in delimiting the cutaneous expression of sympathetic ganglia T2-T3. RESULTS: Redistribution of perspiration as reported by the patients comprised significant reduction in the palms, axillas, and soles, and an increase in the abdomen, back, and gluteal and popliteal regions. Regarding the incidence of anhidrosis by anatomical location, statistically significant changes were recorded in the head, hands, axillas, and soles (p < 0.001). CONCLUSIONS: Bilateral upper thoracic sympathicolysis is followed by redistribution of body perspiration, with a clear decrease in the zones regulated by mental or emotional stimuli, and an increase in the areas regulated by environmental stimuli, though we are unable to establish the etiology of this redistribution.

Thoracic sympathicolysis for primary hyperhidrosis: a review of 918 procedures.

BACKGROUND: Bilateral upper thoracic sympathectomy or sympathicolysis, currently the standard treatment for palmar or axillary hyperhidrosis, is regarded as a safe procedure. This study evaluates the quantitative and qualitative incidence of intraoperative and postoperative complications resulting from bilateral thoracic sympathicolysis. METHODS: From 1996 to 2004, 458 consecutive patients with primary hyperhidrosis underwent surgery. These patients comprised 143 men (31.2%) and 315 women (68.7%) with a mean age of 26 years (range, 14-52 years). In all but seven cases, the procedure was bilaterally synchronous. RESULTS: No mortality was recorded. The anhydrosis rate was 97.4%, with a hypohidrosis rate of 2.4% and a failure rate of 0.2%. The latter was resolved with reintervention. The mean hospital stay was 17 h. The rate of major perioperative complications with conversion to thoracotomy was 0.4%. The overall rate of postoperative complications was 3.6%. The complications and rates observed were as follows: pneumothorax (2.06%), subcutaneous emphysema (1.08%), pleural bleeding (0.2%), hemothorax (0.1%), and atelectasis (0.1%). Compensatory hyperhidrosis was observed in 48.4% of the patients, but the sensation of compensatory hyperhidrosis was reported in 85.6% of the cases. Excessive dryness of the hands was reported in 0.38%, Horner's syndrome in 0.32%, and gustatory hyperhidrosis in 1.1% of the cases. The overall satisfaction rate was 88.5%. CONCLUSIONS: The results suggest that endoscopic bilateral thoracic sympathicolysis is an effective method for managing primary hyperhidrosis, especially severe palmar hyperhidrosis, but it is necessary to inform patients fully concerning the undesirable effects.

[Results of high bilateral endoscopic thoracic sympathectomy and sympatholysis in the treatment of primary hyperhidrosis: a study of 1016 procedures]. / Resultados de la simpaticólisis y la simpatectomía torácica superior bilateral endoscópica en el tratamiento de la hiperhidrosis primaria. Estudio de 1.016 procedimientos.

OBJECTIVE: Thoracic sympatholysis and sympathectomy are the current standard treatments for primary hyperhidrosis. In this study, we evaluated the incidence of peri- and postoperative complications associated with these procedures. PATIENTS AND METHODS: From 1996 to 2004, 520 consecutive patients (364 women), with a mean age of 26.8 years, were treated for primary hyperhidrosis at our hospital. The procedure was bilateral in all but 24 cases. The 484 patients in the sympatholysis group underwent a single intervention while the 36 patients in the sympathectomy group underwent 2 separate interventions. RESULTS: No deaths occurred. Anhidrosis of the target area was achieved in 97.6% of patients while 2.2% experienced hypohidrosis. In 0.2% of the cases, the procedure was initially unsuccessful and a second intervention was required. The mean duration of hospital stay was 72 hours for patients in the sympathectomy group and 17 hours for the sympatholysis group. Serious intraoperative complications requiring conversion to thoracotomy were recorded in 0.2% of patients. Postoperative complications--of which pneumothorax was the most common--occurred in 5.2% of the cases (in 22.5% of the sympathectomy group and 3.55% of the sympatholysis group). Compensatory hyperhidrosis occurred in 48.4% of the patients, excessive dryness of the hands and palpebral ptosis in 0.38%, and gustatory sweating in 0.9%. The degree of patient satisfaction was quite high (88.5%) and only 2.3% were very unsatisfied. CONCLUSIONS: Given the results obtained, we can conclude that both sympatholysis and sympathectomy are appropriate treatments for hyperhidrosis. Nonetheless, because sympatholysis is both easier to perform and less aggressive, we consider it the treatment of choice for primary hyperhidrosis.

[Primary hyperhidrosis and anxiety: a prospective preoperative survey of 158 patients]. / Hiperhidrosis primaria y ansiedad: estudio prospectivo preoperatorio de 158 pacientes.

OBJECTIVE: To determine the location of hyperhidrosis, the accompanying signs and symptoms, and patient anxiety assessed on 2 scales and standardized psychometric instruments. PATIENTS AND METHODS: A prospective study of patients with hyperhidrosis was carried out between September 1, 2001 and June 30, 2003 with a self-administered preoperative questionnaire. The variables studied included the location of hyperhidrosis, the accompanying signs and symptoms, and the self-reported degree of anxiety and perception of its effect on daily life assessed by the State-Trait Anxiety Inventory (STAI) and a questionnaire designed in our department. RESULTS: Palmar hyperhidrosis was reported by 93.6% of patients, plantar by 70.2%, axillary by 66.4%, facial by 12.1%, groin by 8.2%, chest by 5%, and abdominal by 2%. While more than 50% of the patients reported facial blushing and palpitations as accompanying signs and symptoms, approximately 30% experienced epigastric pain, trembling, and headaches. Over half of the patients reported that their anxiety was incapacitating, and a mere 1.2% experienced none at all. STAI scores were similar to those of the general population whereas scores on our department's questionnaire reflected those of the self-reported anxiety ratings. CONCLUSIONS: Primary hyperhidrosis is a disorder in which excessive sweating occurs mainly, but not exclusively, on the palms. The condition is accompanied by signs and symptoms typical of autonomic nervous system hyperactivity and by a degree of anxiety that has an incapacitating effect on normal life, although that anxiety is not detected by the STAI questionnaire alone.

Amperometric magnetoimmunosensor for ErbB2 breast cancer biomarker determination in human serum, cell lysates and intact breast cancer cells.

A highly sensitive amperometric magnetoimmunosensor for the determination of ErbB2 protein, a well-known biomarker related to high-impact high-incidence diseases such as breast cancer, is described. A sandwich format involving the covalent immobilization of a specific capture antibody onto magnetic beads (MBs) and incubation of the modified MBs with a mixture solution of the antigen and a HRP-labeled detector antibody was used. The resulting modified MBs were captured on the surface of a disposable screen-printed carbon electrode (SPCE) and the amperometric responses at -0.20 V were measured. This ErbB2 magnetoimmunosensor exhibited a very low detection limit of 26 pg mL(-1) far below the established cut-off for this biomarker (15 ng mL(-1)) and was successfully applied to the quantitation of ErbB2 in human serum and cell lysates samples without any matrix effect. In addition, the developed assay allowed the assessment of ErbB2 status directly in intact breast cancer cells. The results correlated well with those obtained with a commercial ELISA method, thus demonstrating that the new magnetoimmunosensing platform offers a truthful and useful analytical tool to be easily applied in breast cancer diagnosis through either ErbB2 protein determination or breast cancer cell status detection.

[Histopathological changes in sympathetic ganglia of patients treated surgically for palmar-axillary hyperhidrosis. A study of 55 biopsies]. / Cambios anatomopatológicos observados en los ganglios simpáticos de pacientes intervenidos de hiperhidrosis palmar-axilar. Estudio de 55 muestras.

INTRODUCTION: Primary palmar hyperhidrosis (PPH) mainly affects the sympathetic ganglia. This study aims to analyze the histopathological changes in the sympathetic ganglia of patients with PPH. MATERIAL AND METHOD: We studied 55 tissue samples from 35 patients with PPH who underwent T2-T3 gangliectomy for definitive treatment of their disease, analyzing the presence of inflammation, chromatolysis and lipofuscin accumulation. Findings were analyzed in relation to age, compensatory sweating and type of surgery: unilateral, synchronic bilateral or sequential bilateral. RESULTS: We found inflammation in 5.5%, chromatolysis in 61.8% and lipofuscin accumulation in 41.8% of the samples. Chromatolysis and lipofuscin were found without inflammation in 32.1%. Chromatolysis and lipofuscin accumulation were each found in 60% of the samples from synchronic bilateral sympathectomies. However, those percentages decreased between the first and second sympathectomies in sequential procedures, such that chromatolysis was found in 71.4% of first-procedure samples and 42.8% of second-procedure samples; the rates for lipofuscin accumulation changed from 64.2% to 14.2%. Although findings were unrelated to age, they did correlate with compensatory sweating, which was found in 79.7% of patients undergoing synchronic bilateral sympathectomy, 78.5% of sequential bilateral sympathectomy patients and only 56.25% of unilateral sympathectomy patients. CONCLUSIONS: Neuronal death and lipofuscin accumulation unrelated to inflammation are evident in sympathetic ganglia from patients with PPH. Such changes are atypical for a group of patients whose mean age is 29 years, unless such lesions are the result of functional hyperstimulation. Surgery performed sequentially does not lead to overloading of contralateral T2-T3 ganglia; on the contrary, decreased injury is evident.

[Compensatory sweating after upper thoracic sympathectomy. Prospective study of 123 cases]. / Sudación compensatoria secundaria a la simpaticólisis torácica superior. Estudio prospectivo de 123 casos.

OBJECTIVE: The most unpleasant consequence of upper thoracic sympathectomy is compensatory sweating (CS). De-pending on the series, the incidence of CS ranges from 24% to 85%. The aim of this study was to determine the relation between CS and the following factors: distribution of hyperhidrosis, procedure performed (unilateral, synchronic bilateral, or sequential bilateral), and number of sympathetic ganglia eliminated. In addition, the degree of patient satisfaction was recorded as objectively as possible. PATIENTS AND METHODS: Prospective study of 123 patients who underwent upper thoracic sympathectomy for palmar and/or axillary hyperhidrosis between 1 January, 1996 and 1 June, 2002 at our unit. All patients completed a questionnaire on symptoms 8 weeks before and after surgery to deter-mine postoperative changes in distribution of the hyperhidrosis and the overall degree of satisfaction on a scale of 0 to 4. RESULTS: The sensation of CS was reported by 86.1% of the patients. When asked to relate this sensation to changes in sweating intensity in specific parts of the body, 46.54% reported CS and 48.37% no change. The trunk was the only region where statistically significant increases in CS occurred; in the feet, a decrease in sweating was noted. No differences in CS were observed with respect to the type of surgery or the number of sympathetic ganglia eliminated. The overall results were considered very satisfactory or quite satisfactory by 84.55% of the patients, while 4.88% were very dissatisfied. CONCLUSIONS: Although CS is a side effect of upper thoracic sympathectomy, not all patients are affected by it. Significant CS occurs mainly in the back, chest, and abdomen. Neither the type of intervention nor the number of ganglia eliminated has an effect on CS. This side effect notwithstanding, overall satisfaction with the treatment is very satisfactory given that the palmar hyperhidrosis is eliminated.

[Ineffectiveness of incentive spirometry as coadjuvant of conventional physiotherapy for the prevention of postoperative respiratory complications after thoracic and esophageal surgery]. / Ineficacia de la espirometría incentiva como coadyuvante de la fisioterapia convencional en la prevención de las complicaciones respiratorias postoperatorias de la cirugía torácica y esofágica.

We have studied the efficacy of routine use of incentive spirometry (IS) in two groups of patients: group 1 (n = 18) with IS, and group 2 (n = 19), no IS. All patients suffered from lung or esophagus neoplasm and received respiratory physiotherapy before and after the operation. They underwent high chest and abdomen surgery. The incidence of alterations of pulmonary auscultation, roentgenologic abnormalities and alterations of the alveolar-arterial difference of oxygen (D[A-a]O2) as well as postoperative complications were similar in both groups. Patients undergoing digestive surgery presented a higher frequency of pleural effusion (p less than 0.05) and of them, the subgroup with IS stayed at the hospital for a longer time (47.2 +/- 32 days) than the subgroup undergoing digestive surgery not submitted to IS (p less than 0.01) probably because of the higher incidence of neoplasms of the mean third of the esophagus in such group. In our study and in the context of the type of surgery studied, the routine use of IS does not decrease the frequency of clinical and roentgenologic alterations neither improves the efficacy of postoperative gas interchange.

[Hemothorax as complication of laparoscopic technique]. / Un hemotórax como complicación de la técnica laparoscópica.

A 69-year-old woman with a hiatal hernia and esophagitis caused by reflux was scheduled for laparoscopic Nissen fundoplication. Anesthetic induction was accomplished with fentanyl, propofol and rocuronium and maintenance with sevoflurane and rocoronium. Hemodynamics were stable until the end of surgery, when a sudden decrease in blood pressure to 40/20 mm Hg and arterial carbon dioxide tension to 14 mm Hg were observed. Anesthetic insufflation was stopped and physiological saline solution and ephedrine were administered. Hemothorax and air embolism were ruled out. After hemodynamic recovery, renewal of anesthetic insufflation was contraindicated, laparoscopy was halted, and hemoperitoneum was ruled out. After extubation, the patient was transferred to the recovery room, where hemodynamic instability worsened progressively. A chest radiograph suggest left hemothorax and an emergency thoracotomy was performed. After evacuation of multiple clots from the pleural cavity, the point of hemorrhage was located at the right crus of the diaphragm and bleeding was arrested. Postoperative recovery continued with no further events. The most common complications of laparoscopy are pneumothorax, gastroesophageal perforation and hemorrhage. However, given the complexity of the technique, the possibility of bleeding in the pleural cavity, as occurred in this case, should be considered. This case highlights the importance of rigorous intraoperative monitoring and postoperative surveillance by the anesthesiologist.

[Usefulness of pulse oximetry in thoracic surgery]. / Utilidad de la pulsioximetría en cirugía torácica.

Saturation of hemoglobin in arterial blood was simultaneously measured by co-oximetry (SaO2) and by pulse oximetry (SpO2) in 228 samples from 42 patients undergoing general anesthesia for thoracic surgery. Data was referred to SaO2 obtained with arterial catheterization. We found a significant correlation (r: 0.949 and p less than 0.001) and the mean differences were 0.77 +/- 1.84. The correlation between PaO2 and the difference among both methods was significantly negative (r: -0.20; p less than 0.001). Although there was a significant correlation, the method loses reliability and accuracy in patients with hypoxemia. In these patients oximetric values are slightly lower than those obtained with arterial cannulation. We emphasize the clinical usefulness of this technique since it is instantaneous and allowed immediate therapeutic actions.

[Prevention of cross contamination, patient to anesthesia apparatus to patient, using filters]. / Profilaxis de la contaminación cruzada, enfermo-aparato de anestesia-enfermo, mediante filtros.

Concern for cross infections from patient to patient via apparatus is particularly relevant today. There are several ways to prevent patient contamination through anesthetic devices. Although there is no clinical evidence for using one alternative over another and each hospital establishes its own hygienic protocols, we have introduced the systematic use of filters with patients undergoing general anesthesia. We describe the features of filters available on the market and our protocol for their use. The efficacy of a filter depends on whether bacteria or viruses are to be controlled. Filters can be classified into three groups or generations based on mesh quality: 1) heat and humidity exchangers (HHE), with large mesh screens that allow water to pass through; 2) bacterial filters (FHHE), with finer mesh that is permeable to droplets of water and 3) folded membrane filters (FHHE) that are hydrophobic, with very fine mesh that stops water. We describe three basic physical tests (passage of water, passage of smoke and increase of resistance when applied to the patient) for filters to be classified. The ideal filter is hydrophobic and does not increase circuit resistance over the amount specified. Four principles are emphasized in the protocol: 1) the filter forms a part of the patient, not the apparatus; 2) proper placement of the filter is between the patient and the circuit's "Y" piece; 3) the main purpose of the filter is to prevent contamination of the apparatus, and 4) if a hydrophobic filter is used with each patient, the use of a disposable respiratory circuit is not called for.

Biosensors in forensic analysis. A review.

Forensic analysis is an important branch of modern Analytical Chemistry with many legal and socially relevant implications. Biosensors can play an important role as efficient tools in this field considering their well known advantages of sensitivity, selectivity, easy functioning, affordability and capability of miniaturization and automation. This article reviews the latest advances in the use of biosensors for forensic analysis. The different methodologies for the transduction of the produced biological events are considered and the applications to forensic toxicological analysis, classified by the nature of the target analytes, as well as those related with chemical and biological weapons critically commented. The article provides several Tables where the more relevant analytical characteristics of the selected reported methods are gathered.

Amperometric magnetoimmunoassay for the direct detection of tumor necrosis factor alpha biomarker in human serum.

An amperometric immunoassay for the determination of tumor necrosis factor alpha (TNFα) protein biomarker in human serum based on the use of magnetic microbeads (MBs) and disposable screen-printed carbon electrodes (SPCEs) has been developed. The specifically modified microbeads were magnetically captured on the working electrode surface and the amperometric responses were measured at -0.20V (vs. Ag pseudo-reference electrode), upon addition of hydroquinone (HQ) as electron transfer mediator and H2O2 as the enzyme substrate. After a thorough optimization of the assay, extremely low limits of detection were achieved: 2.0pg mL(-1) (36fM) and 5.8pg mL(-1) (105fM) for standard solutions and spiked human serum, respectively. The simplicity, robustness and this clinically interesting LOD proved the developed TNFα immunoassay as a good contender for real clinical application.

Anti-inflammatory properties of superoxide dismutase modified with carboxymetil-cellulose polymer and hydrogel.

Superoxide dismutase (SOD) was chemically bound to carboxymethyl-cellulose (CMC) polymer.Furthermore, SOD was also trapped into two hydrogels of CMC with 50% and 90% crosslinking degree. The ability of the two SOD-CMC hydrogels to capture SOD and their release kinetics were investigated. ATR FT-IR spectrometry was used to study the conformation of SOD interacting with both CMC polymer and hydrogels. The effect of SOD-CMC polymer conjugate and SOD-CMC hydrogel systems upon human fibroblasts was studied in vitro measuring the cell proliferation inhibition index and evaluating cell morphology. Using the xanthine oxidase-nitroblue tetrazolium assay, the specific activity of bound SOD to CMC polymer or trapped into hydrogels was evaluated. The specific activity of the enzyme was higher in SOD-CMC hydrogels than in SOD-CMC polymer conjugates.