Antimicrobial peptide dendrimer interacts with phosphocholine membranes in a fluidity dependent manner: A neutron reflection study combined with molecular dynamics simulations.

The interaction mechanism of a novel amphiphilic antimicrobial peptide dendrimer, BALY, with model lipid bilayers was explored through a combination of neutron reflection and molecular dynamics simulations. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dipalmitoyl-sn-glycero-3-phos-phocholine (DPPC) lipid bilayers were examined at room temperature to extract information on the interaction of BALY with fluid and gel phases, respectively. Furthermore, a 1:4 mixture of POPC and DPPC was used as a model of a phase-separated membrane. Upon interaction with fluid membranes, BALY inserted in the distal leaflet and caused thinning and disordering of the headgroups. Membrane thinning and expansion of the lipid cross-sectional area were observed for gel phase membranes, also with limited insertion to the distal leaflet. However, dendrimer insertion through the entire lipid tail region was observed upon crossing the lipid phase transition temperature of DPPC and in phase separated membranes. The results show clear differences in the interaction mechanism of the dendrimer depending on the lipid membrane fluidity, and suggest a role for lipid phase separation in promoting its antimicrobial activity.

Voltage-Gated Sodium Channels: Mechanistic Insights From Atomistic Molecular Dynamics Simulations.

The permeation of ions and other molecules across biological membranes is an inherent requirement of all cellular organisms. Ion channels, in particular, are responsible for the conduction of charged species, hence modulating the propagation of electrical signals. Despite the universal physiological implications of this property, the molecular functioning of ion channels remains ambiguous. The combination of atomistic structural data with computational methodologies, such as molecular dynamics (MD) simulations, is now considered routine to investigate structure-function relationships in biological systems. A fuller understanding of conduction, selectivity, and gating, therefore, is steadily emerging due to the applicability of these techniques to ion channels. However, because their structure is known at atomic resolution, studies have consistently been biased toward K(+) channels, thus the molecular determinants of ionic selectivity, activation, and drug blockage in Na(+) channels are often overlooked. The recent increase of available crystallographic data has eminently encouraged the investigation of voltage-gated sodium (NaV) channels via computational methods. Here, we present an overview of simulation studies that have contributed to our understanding of key principles that underlie ionic conduction and selectivity in Na(+) channels, in comparison to the K(+) channel analogs.

Molecular dynamics simulations and neutron reflectivity as an effective approach to characterize biological membranes and related macromolecular assemblies.

In combination with other spectroscopy, microscopy, and scattering techniques, neutron reflectivity is a powerful tool to characterize biological systems. Specular reflection of neutrons provides structural information at the nanometer and subnanometer length scales, probing the composition and organization of layered materials. Currently, analysis of neutron reflectivity data involves several simplifying assumptions about the structure of the sample under study, affecting the extraction and interpretation of information from the experimental data. Computer simulations can be used as a source of structural and dynamic data with atomic resolution. We present a novel tool to compare the structural properties determined by neutron reflectivity experiments with those obtained from molecular simulations. This tool allows benchmarking the ability of molecular dynamics simulations to reproduce experimental data, but it also promotes unbiased interpretation of experimentally determined quantities. Two application examples are presented to illustrate the capabilities of the new tool. The first example is the generation of reflectivity profiles for a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayer from molecular dynamics simulations using data from both atomistic and coarse-grained models, and comparison with experimentally measured data. The second example is the calculation of lipid volume changes with temperature and composition from all atoms simulations of single and mixed 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC) bilayers.

Partition coefficients of indoles and betacarbolines.

Partition coefficients for substituted indoles and betacarbolines were determined in octan-1-ol/water and cyclohexane/water. A comparative study of the results in both systems allows us to discuss the effects played by the different molecular structures, substituents, and aromaticity on the distribution properties of these compounds. In particular, the hydrogen-bond donor (HBD) and hydrogen-bond acceptor (HBA) properties of these solutes were characterized and compared with those of structurally related compounds. The Abraham solute descriptors were estimated and partition coefficients (log P) calculated and compared with the experimental values. The results show that the HBD properties are similar for indoles and betacarbolines, and the HBA capacity, as expected, is significantly enhanced by the contribution of the extra pyridinic or piperidinic ring in betacarbolines. The effects of the substituent groups are presented in relation to their contribution to the distribution properties of the compounds studied.

Laparoscopic treatment of traumatic diaphragmatic hernia.

Traumatic diaphragmatic hernia is rare, but is of utmost importance due to its high morbidity and mortality. It is markedly important in patients with blunt abdominal trauma, and diagnosis is difficult because of the numerous associated injuries. A patient with few symptoms of chronic traumatic diaphragmatic hernia is described, who underwent surgery due to a gastric volvulus. Laparoscopic surgery permits repair of these injuries through an abdominal approach, avoiding a thoracic incision or selective intubation.

[Spontaneous perforation of the cecum without colonic obstruction. Report of 3 cases]. / Perfuração espontânea do ceco sem obstrução cólica. Relato de três casos.

Spontaneous perforation of the colon without obstruction is related to intestinal and extra intestinal diseases, mainly gynecological procedures. Its etiology is unknown, and there are many theories. Because of its diagnosis peculiarities, as well as its rarity, and mainly the severity of the disease, the authors describe three cases, relating the necessity of early diagnosis and correct surgical treatment.

Videolaparoscopic cholecystectomy. Analysis of the clinical and functional aspects of mechanical lifting of the abdominal wall.

BACKGROUND: Mechanical lifting of the abdominal wall, a method based on traction and consequent elevation of the abdominal wall, is an alternative procedure to create enough intra-abdominal space necessary for videolaparoscopic surgery, dispensing the need for intraperitoneal gas insufflation. OBJECTIVE: This study aims to evaluate the technical feasibility of this procedure to carry out a videolaparoscopic cholecystectomy, while analyzing the clinical and functional aspects of this technique. PATIENTS AND METHODS: In the Digestive Tract Surgery Discipline of the Medical School at the University of São Paulo, São Paulo, SP, Brazil, was created the equipment to perform videolaparoscopic surgery using this method. The equipment has two sections: an external part which consisted of a frame attached to the operating table, inside which there is a sliding steel cable, moved by a ratched which is located at the lower end of one of the frame rods; the internal rod, the support, has an "L" shape, and its horizontal branch is made up of three turning rods and which is connected to the steel cable after insertion into the abdominal cavity. Ten patients underwent videolaparoscopic cholecystectomy using this equipment. The time taken to install the equipment, the operating area characteristics, the interference from the lifting equipment on surgical movements and on the intra-operative cholangiography, the measurements made of the force used during traction and extension of the abdominal wall elevation, and the medication required for postoperative analgesia were all evaluated. RESULTS: There were no intra-operative complications, and in none of the cases was it found necessary to convert to open surgery. We considered the insertion a safe and uncomplicated procedure, and the traction system efficient. Apart from the elevation of the abdominal wall, the distribution of the viscera inside the abdominal cavity is fundamental for the operating area. Depending on the position of the epigastric trocar, the lifting equipment can interfere with the surgical instruments mobility. It may be necessary to reposition the support to perform the intra-operative cholangiography. The tensional force applied to the peritoneal surface by the lifting rods is small, and no additional postoperative pain was observed using this procedure. CONCLUSION: These results show that using the equipment described in this study, mechanical lifting of the abdominal wall is a feasible alternative for undertaking videolaparoscopic cholecystectomy.

[Training of surgeons in laparoscopic surgery of the digestive system. Experience in 1,818 interventions without accidents and mortality]. / Formação do cirurgião em cirurgia laparoscópica do aparelho digestivo. Experiência de 1.818 intervenções sem acidentes e sem mortalidade.

UNLABELLED: Since the beginning or laparoscopic surgery on University of Sao Paulo Medical School Clinics Hospital, the Digestive Surgery Division established an educational program for surgeons of the alimentary tract. PURPOSE: The course structure includes the information on medical school, extension in laparoscopic surgery league, and surgical formation during the residence, mainly in the fourth year, with a three months period in the Laparoscopic Surgery Unit. METHOD: This model of surgical formation is certainly responsible for the excellent results obtained. RESULTS: An example is the performing of 1818 cholecystectomies in the Laparoscopic Surgery Unit from 1990 till 1998, with 0.9% convertion, and no mortality. The absence of operative accidents or complications give support to the orientation assumed in our Division. CONCLUSION: In a university hospital there is the necessity of professional formation in a well structured program, with humanistic and technical education, in a large period of rotation, but with a solid information and practical structure.

[Synchronous esophageal and stomach neoplasm: importance of diagnosis and treatment]. / Neoplasias sincrônicas de esôfago e estômago: importância diagnóstica e terapêutica.

The association of esophageal and gastric cancer has been described because of the better technology in methods for diagnosis. In surgery for esophageal cancer, a gastric tube is often prepared to provide a new route for oral ingestion. Although patients with simultaneous esophageal cancer and gastric cancer have been reported, it is often difficult to diagnose the coexistence of gastric cancer preoperatively due to the presence of esophageal stenosis. In this paper we report on one case of the rare combination of squamous cell cancer of the esophagus and simultaneous adenocarcinoma of the stomach.

[Esophagectomy using videosurgery]. / Esofagectomia por videocirurgia]

This is a report of 10 cases of esophagetomy by videosurgery. Five patients had esophageal carcinoma and five had achalasia. The patients who had neoplasia were submitted to thoracoscopic, laparoscopic and cervicotomy and the others who had benign pathology were submitted to laparoscopic with transdiafragmatic approach and cervicotomy. The evolution was very satisfactory but there were complications that had no relation with the method. The follow up is being made and we have no sure about real results.

[Acute appendicitis following laparoscopic inguinal hernioplasty. Coincidence or complication?]. / Apendicite aguda após hernioplastia inguinal laparoscópica: coincidência ou complicação?

Intraperitoneal complications related to laparoscopic inguinal hernia repair by transabdominal approach had been described. The authors report the first case of postoperative acute appendicitis in a patient submitted to a transuretral prostate resection and bilateral inguinal hernioplasty by the TAPP technique, resulting in a second laparoscopic intervention.

[Esophageal intubation for palliative treatment in advanced carcinoma of the esophagus and cardia]. / Tunelização esofágica no tratamento paliativo do câncer avançado do esôfago e da cárdia.

This is a report of 121 cases of advanced esophageal and cardia cancer managed by endoscopic and surgical esophageal intubation. They were submitted to surgical intubation 69 (53%) patients, and 52 (47%) to endoscopic intubation. There were 32.5% of technical complications in endoscopic intubation and 26.5% in surgical intubation. Perfuration was more frequent (11.5%) in endoscopic intubation than surgical group. Mortality rate was 17.3% for endoscopic and 5.8% for surgical intubation. Perfuration was the main cause of death in endoscopic intubation. Survival rate was 3.5 months for endoscopic and 4.7 months for surgical intubation. The majority of patients died of cancer evolution--caquexia (55.5%), carcinomatosis (4.5%) and brain methastasis (1.1%). The results of endoscopic and surgical intubation in this group of patients recommend its use in patients with advanced esophageal and cardic cancer.

[Infantile diarrhea: knowledge and attitudes of mothers at a primary care center]. / Diarrea en la infancia: conocimientos y actitudes de las madres en un centro de atención primaria.

OBJECTIVE: To study the knowledge and attitudes of mothers at a health centre to babies' diarrhoea. DESIGN: A crossover, observational and prospective study. SETTING: Paediatrics clinic at a health centre in the city of Valencia. PARTICIPANTS: 142 mothers who attended the clinic of their own accord. MEASUREMENTS AND MAIN RESULTS: The mothers themselves filled out a questionnaire on what diarrhoea was, its causes, hygiene measures to prevent it and their response when it appeared. 80.3% accurately defined diarrhoea. 94.4% recognised that micro-organisms were the cause. All mothers of unweaned babies not being breast-fed sterilised the feeding bottle adequately and had a proper water-supply. 89.4% said they washed correctly both hands and food before handling food. Although 89.4% knew they should give more liquid to their babies during diarrhoea, only 24.6% used an adequate oral rehydrating solution and 24.2% said they made their babies fast for long periods. Most said they would consult the doctor if their baby had diarrhoea (79.6%) and would go back to the doctor if they noticed complications (96.5%). CONCLUSIONS: Mothers attending a health centre in Valencia had a good attitude to diarrhoea prevention. They often committed errors in oral rehydration and feeding of a baby with diarrhoea, which might cause problems. However their frequent attendance at the doctor's may help avoid these problems.

[Laparoscopic repair of chronic traumatic diaphragmatic hernia: case report and review of the literature]. / Correção laparoscópica de hérnia difragmática traumática crônica: relato de caso revisão da literatura.

The management of diaphragmatic injury would appear to be a simple matter of suturing the defect. However, preoperative diagnosis can be difficult and even at the time of surgery some diaphragmatic injuries can be overlooked if careful exploration in not done. Associated injuries tend to divert attention from the diaphragmatic injury. Laparoscopic diagnosis and repair have been described with successful.

[Reconstruction of a thoracic wall defect using a flap of omentum obtained by laparoscopy]. / Obtenção de retalho de epíplon por via laparoscópica para reconstrução de defeito da parede torácica.

Reconstructive of complex chest wall defects following infected sternotomy represents a surgical challenge. Several options were described for these defects reconstructions, using muscles flaps and omentum which provided obliteration of dead space and coverage. We present a reconstruction of a major chest and abdominal wall defect in a 62-year old patient, who had mediastinitis, osteomyelitis and necrosis of sternum after myocardial revascularization. The pectoralis major was used unsuccessfully, with total loose of the flap. After wound failure, a flap of omentum based on the left gastroepiploic vessels was obtained by a laparoscopic surgery, with no complication. The omentum was translocated through the defect that reached the abdominal wall covering the defect and allowing the use of split-thickness grafts. The laparoscopic procedure showed advantages over the laparotomy in the management of omentum, with the same results in the reconstruction of the defect added the advantages of a minimal invasive procedure, mainly in patient with bad clinical conditions.

Omental flap obtained by laparoscopic surgery for reconstruction of the chest wall.

The reconstruction of complex defects of the chest wall after infection of the sternotomy wound presents a great challenge. Various options have been described for these reconstructions using muscle and omental flaps to fill the space and cover the defect. A case of reconstruction of a large defect of the chest cage and abdominal wall in a 62-year-old patient is presented. After surgery for revascularization of the myocardium, the patient developed mediastinitis, osteomyelitis, and necrosis of the sternum. The pectoralis major muscle was utilized for the reconstruction, but total loss of the flap occurred. After débridement, an omental flap obtained by laparoscopy was employed based on the left gastroepiploic artery. The omentum was transposed without complications through the abdominal wall defect. An overlay skin graft with the omentum as receptor bed completed the closure. There are advantages in using minimally invasive videolaparoscopy compared with laparotomy in obtaining the omentum, with the same result regarding reconstruction of the defect.

p21Waf1/Cip1 expression is a prognostic marker in curatively resected esophageal squamous cell carcinoma, but not p27Kip1, p53, or Rb.

BACKGROUND: p21Waf1/Cip1 (p21), p27Kip1 (p27), p53, and Rb play critical roles in cell cycle regulation and may influence the clinical behavior of tumors. We examined whether their expression is useful to predict survival of patients with esophageal squamous cell carcinoma (ESC). METHODS: Expression of p21, p27, p53, and Rb was studied by the immunohistochemical method in specimens from 62 patients with curatively resected ESC tumors and scored by a computerized image analysis system. RESULTS: The median expression scores of p21, p27, p53, and Rb (14, 12, 27, and 50, respectively) were used as cut-off points to define low and high expression groups for each protein. The 5-year survival rate for the high p21 expression group was 68%; that for the low expression group was 31% (P = .0062). p27, p53, and Rb were not correlated with overall survival. When patients were categorized into four groups based on p21 expression level and lymph node involvement (pN), the survival curves were significantly different (P = .0017). Thus, patients without lymph node involvement but with low p21 expression had survival similar to that of patients with lymph node involvement and high p21 expression. Multivariate analysis showed that age (P = .0102), lymph node involvement (P = .0076), and p21 (P = .0276) were independent prognostic factors. CONCLUSIONS: Expression of p21 is an independent prognostic factor in curatively resected ESC. Definition of new subgroups of patients based on p21 expression may help to enhance the stratification of stage.

[Videolaparoscopic treatment of hepatic single cysts]. / Tratamento videolaparoscópico dos cistos simples de fígado.

We report a study of 6 patients with simple hepatic cyst. All were underwent laparoscopic surgical treatment. The median age of patients was 66 years, 5 women and 1 man were in the series. Cyst diameters varied from 3 to 15 cm. The treatment of choice is laparoscopic fenestration and resection of external part. There were no complications in postoperative period and the follow-up results are encouraging.