Charge generation, charge transport, and residual charge in the electrospinning of polymers: A review of issues and complications

Electrospinning has become a widely implemented technique for the generation of nonwoven mats that are useful in tissue engineering and filter applications. The overriding factor that has contributed to the popularity of this method is the ease with which fibers with submicron diameters can be produced. Fibers on that size scale are comparable to protein filaments that are observed in the extracellular matrix. The apparatus and procedures for conducting electrospinning experiments are ostensibly simple. While it is rarely reported in the literature on this topic, any experience with this method of fiber spinning reveals substantial ambiguities in how the process can be controlled to generate reproducible results. The simplicity of the procedure belies the complexity of the physical processes that determine the electrospinning process dynamics. In this article, three process domains and the physical domain of charge interaction are identified as important in electrospinning: (a) creation of charge carriers, (b) charge transport, (c) residual charge. The initial event that enables electrospinning is the generation of region of excess charge in the fluid that is to be electrospun. The electrostatic forces that develop on this region of charged fluid in the presence of a high potential result in the ejection of a fluid jet that solidifies into the resulting fiber. The transport of charge from the charge solution to the grounded collection device produces some of the current which is observed. That transport can occur by the fluid jet and through the atmosphere surrounding the electrospinning apparatus. Charges that are created in the fluid that are not dissipated remain in the solidified fiber as residual charges. The physics of each of these domains in the electrospinning process is summarized in terms of the current understanding, and possible sources of ambiguity in the implementation of this technique are indicated. Directions for future research to further articulate the behavior of the electrospinning process are suggested. (C) 2012 American Institute of Physics. [doi: 10.1063/1.3682464]

A general framework for multi-compartmental analysis of drug chemotherapy dynamics in human immunodeficiency virus type-1 infected individuals

An optimal control strategy for the highly active antiretroviral therapy associated to the acquired immunodeficiency syndrome should be designed regarding a comprehensive analysis of the drug chemotherapy behavior in the host tissues, from major viral replication sites to viral sanctuary compartments. Such approach is critical in order to efficiently explore synergistic, competitive and prohibitive relationships among drugs and, hence, therapy costs and side-effect minimization. In this paper, a novel mathematical model for HIV-1 drug chemotherapy dynamics in distinct host anatomic compartments is proposed and theoretically evaluated on fifteen conventional anti-retroviral drugs. Rather than interdependence between drug type and its concentration profile in a host tissue, simulated results suggest that such profile is importantly correlated with the host tissue under consideration. Furthermore, the drug accumulative dynamics are drastically affected by low patient compliance with pharmacotherapy, even when a single dose lacks. (C) 2012 Elsevier Inc. All rights reserved.

Cytokine Balance in Human Malaria: Does Plasmodium vivax Elicit More Inflammatory Responses than Plasmodium falciparum?

Background: The mechanisms by which humans regulate pro-and anti-inflammatory responses on exposure to different malaria parasites remains unclear. Although Plasmodium vivax usually causes a relatively benign disease, this parasite has been suggested to elicit more host inflammation per parasitized red blood cell than P. falciparum. Methodology/Principal Findings: We measured plasma concentrations of seven cytokines and two soluble tumor necrosis factor (TNF)-alpha receptors, and evaluated clinical and laboratory outcomes, in Brazilians with acute uncomplicated infections with P. vivax (n = 85), P. falciparum (n = 30), or both species (n = 12), and in 45 asymptomatic carriers of low-density P. vivax infection. Symptomatic vivax malaria patients, compared to those infected with P. falciparum or both species, had more intense paroxysms, but they had no clear association with a pro-inflammatory imbalance. To the contrary, these patients had higher levels of the regulatory cytokine interleukin (IL)-10, which correlated positively with parasite density, and elevated IL-10/TNF-alpha, IL-10/interferon (IFN)-gamma, IL-10/IL-6 and sTNFRII/TNF-alpha ratios, compared to falciparum or mixed-species malaria patient groups. Vivax malaria patients had the highest levels of circulating soluble TNF-alpha receptor sTNFRII. Levels of regulatory cytokines returned to normal values 28 days after P. vivax clearance following chemotherapy. Finally, asymptomatic carriers of low P. vivax parasitemias had substantially lower levels of both inflammatory and regulatory cytokines than did patients with clinical malaria due to either species. Conclusions: Controlling fast-multiplying P. falciparum blood stages requires a strong inflammatory response to prevent fulminant infections, while reducing inflammation-related tissue damage with early regulatory cytokine responses may be a more cost-effective strategy in infections with the less virulent P. vivax parasite. The early induction of regulatory cytokines may be a critical mechanism protecting vivax malaria patients from severe clinical complications.

Maternal obesity in high-risk pregnancies and postpartum infectious complications

Objective: To analyze the association between maternal obesity and postnatal infectious complications in high-risk pregnancies. Methods: Prospective study from August 2009 through August 2010 with the following inclusion criteria: women up to the 5th postpartum day; age L 18 years; high-risk pregnancy; singleton pregnancy with live fetus at labor onset; delivery at the institution; maternal weight measured on day of delivery. The nutritional status in late pregnancy was assessed by the body mass index (BMI), with the application of the Atalah et al. curve. Patients were graded as underweight, adequate weight, overweight, or obese. Postpartum complications investigated during the hospital stay and 30 days post-discharge were: surgical wound infection and/or secretion, urinary infection, postpartum infection, fever, hospitalization, antibiotic use, and composite morbidity (at least one of the complications mentioned). Results: 374 puerperal women were included, graded according to the final BMI as: underweight (n = 54, 14.4%); adequate weight (n = 126, 33.7%); overweight (n = 105, 28.1%); and obese (n = 89, 23.8%). Maternal obesity was shown to have a significant association with the following postpartum complications: surgical wound infection (16.7%, p = 0.042), urinary infection (9.0%, p = 0.004), antibiotic use (12.3%, p < 0.001), and composite morbidity (25.6%, p = 0.016). By applying the logistic regression model, obesity in late pregnancy was found to be an independent variable regardless of the composite morbidity predicted (OR: 2.09; 95% CI: 1.15-3.80, p = 0.015). Conclusion: Maternal obesity during late pregnancy in high-risk patients is independently associated with postpartum infectious complications, which demonstrates the need for a closer follow-up of maternal weight gain in these pregnancies.

Drug-targeting in combined cancer chemotherapy: tumor growth inhibition in mice by association of paclitaxel and etoposide with a cholesterol-rich nanoemulsion

Lipid nanoemulsions (LDE) may be used as carriers of paclitaxel (PTX) and etoposide (ETP) to decrease toxicity and increase the therapeutic action of those drugs. The current study investigates the combined chemotherapy with PTX and ETP associated with LDE. Four groups of 10-20 B16F10 melanoma-bearing mice were treated with LDE-PTX and LDE-ETP in combination (LDE-PTX + ETP), commercial PTX and ETP in combination (PTX + ETP), single LDE-PTX, and single LDE-ETP. PTX and ETX doses were 9 mu mol/kg administered in three intraperitoneal injections on three alternate days. In two control groups mice were treated with saline solution or LDE alone. Tumor growth, metastasis presence, cell-cycle distribution, blood cell counts and histological data were analyzed. Toxicity of all treatments was evaluated in mice without tumors. Tumor growth inhibition was similarly strong in all treatment groups. However, there was a greater reduction in the number of animals bearing metastases in the LDE-PTX + ETP group (30 %) in comparison to the PTX + ETP group (82 %, p < 0.05). Reduction of cellular density, blood vessels and increase of collagen fibers in tumor tissues were observed in the LDE-PTX + ETP group but not in the PTX + ETP group, and in both groups reduced melanoma-related anemia and thrombocytosis were observed. Flow cytometric analysis suggested that LDE-PTX + ETP exhibited greater selectivity to neoplastic cells than PTX-ETP, showing arrest (65 %) in the G(2)/M phase of the cell cycle (p < 0.001). Toxicity manifested by weight loss and myelosuppression was markedly milder in the LDE-PTX + ETP than in the PTX + ETP group. LDE-PTX + ETP combined drug-targeting therapy showed markedly superior anti-cancer properties and reduced toxicity compared to PTX + ETP.

Susceptibilities of the dermatophytes Trichophyton mentagrophytes and T. rubrum microconidia to photodynamic antimicrobial chemotherapy with novel phenothiazinium photosensitizers and red light

Photodynamic antimicrobial chemotherapy (PACT) is a promising alternative to conventional chemotherapy that can be used to treat localized mycosis. The development of PACT depends on identifying effective and selective PS for the different pathogenic species. The in vitro susceptibilities of Trichophyton mentagrophytes and Trichophyton rubrum microconidia to PACT with methylene blue (MB), toluidine blue o (TBO), new methylene blue N (NMBN), and the novel pentacyclic phenothiazinium photosensitizer S137 were investigated. The efficacy of each PS was determined based on its minimal inhibitory concentration (MIC). Additionally, we evaluated the effect of PACT with NMBN and S137 on the survival of the microconidia of both species. 5137 showed the lowest MIC. MIC for S137 was 2.5 mu M both for T. mentagrophytes and T. rubrum, when a light dose of 5J cm(-2) was used. PACT with NMBN (10 mu M and 20J cm(-2)) resulted in a reduction of 4 logs in the survival of the T. rubrum and no survivor of T. mentagrophytes was observed. PACT with S137 at 1 mu M and 20J cm(-2) resulted in a reduction of approximately 3 logs in the survival of both species. When a S137 concentration of 10 mu M was used, no survivor was observed for both species at all light doses (5, 10 and 20J cm(-2)). (C) 2012 Elsevier B.V. All rights reserved.

Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma

Melanoma cells express the platelet-activating factor receptor (PAFR) and, thus, respond to PAF, a bioactive lipid produced by both tumour cells and those in the tumour microenvironment such as macrophages. Here, we show that treatment of a human melanoma SKmel37 cell line with cisplatin led to increased expression of PAFR and its accumulation. In the presence of exogenous PAF, melanoma cells were significantly more resistant to cisplatin-induced cell death. Inhibition of PAFR-dependent signalling pathways by a PAFR antagonist (WEB2086) showed chemosensitisation of melanoma cells in vitro. Nude mice were inoculated with SKmel37 cells and treated with cisplatin and WEB2086. Animals treated with both agents showed significantly decreased tumour growth compared to the control group and groups treated with only one agent. PAFR accumulation and signalling are part of a prosurvival program of melanoma cells, therefore constituting a promising target for combination therapy for melanomas.

Weakness of expiratory muscles and pulmonary complications in malnourished patients undergoing upper abdominal surgery

Background and objective: Malnutrition is prevalent in hospitalized patients and causes systemic damage including effects on the respiratory and immune systems, as well as predisposing to infection and increasing postoperative complications and mortality. This study aimed to assess the impact of malnutrition on the rate of postoperative pulmonary complications, respiratory muscle strength and chest wall expansion in patients undergoing elective upper abdominal surgery. Methods: Seventy-five consecutive candidates for upper abdominal surgery (39 in the malnourished group (MNG) and 36 in the control group (CG)) were enrolled in this prospective controlled cohort study. All patients were evaluated for nutritional status, respiratory muscle strength, chest wall expansion and lung function before surgery. Postoperative pulmonary complications (pneumonia, tracheobronchitis, atelectasis and acute respiratory failure) before discharge from hospital were also evaluated. Results: The MNG showed expiratory muscle weakness (MNG 65 +/- 24 vs CG 82 +/- 22 cm H2O; P < 0.001) and decreased chest wall expansion (P < 0.001), whereas inspiratory muscle strength and lung function were preserved (P > 0.05). The MNG also had a higher incidence of postoperative pulmonary complications compared with the CG (31% and 11%, respectively; P = 0.05). In addition, expiratory muscle weakness was correlated with BMI in the MNG (r = 0.43; P < 0.01). The association between malnutrition and expiratory muscle weakness increased the likelihood of postoperative pulmonary complications after upper abdominal surgery (P = 0.02). Conclusions: These results show that malnutrition is associated with weakness of the expiratory muscles, decreased chest wall expansion and increased incidence of pulmonary complications in patients undergoing elective upper abdominal surgery.

Does Adjunctive Chemotherapy Reduce Remission Rates Compared to Cortisone Alone in Unifocal or Multifocal Histiocytosis of Bone?

Langerhans cell histiocytosis (LCH) is a rare disorder that can affect almost any organ, including bone. Treatment options include local corticosteroid infiltration in isolated bone lesions and oral corticosteroids and chemotherapy in multifocal bone lesions. Several studies show local corticosteroid injection in unifocal bone lesions heal in more than 75% of patients with minimal side effects. Therefore, it is unclear whether chemotherapy adds materially to the healing rate. We therefore compared overall survival, remission rate, and recurrence rate in patients with bone LCH treated with chemotherapy and corticosteroids or corticosteroids alone. We retrospectively reviewed the records of 198 patients with LCH since 1950. Median age at diagnosis was 5 years, male-to-female ratio was 1.33, and the most frequent symptom was local pain (95%). We recorded the disease presentation, demographics, treatment, and clinical evolution of each patient. Minimum followup was 4 months (median, 24 months; range, 4-360 months). The survival rate of the systemic disease group was 76.5% (65 of 85) while the survival rate in the unifocal and multifocal bone involvement groups was 100% at a median 5-year followup. All patients with unifocal bone involvement and 40 of 43 (93%) with multifocal bone involvement had complete remission. One of 30 patients with multifocal bone involvement treated with chemotherapy and oral corticosteroids did not achieve remission whereas two of six receiving only corticosteroids did not achieve remission. Our observations suggest intralesional corticosteroid injection without adjunctive chemotherapy achieves remission in unifocal bone LCH but may not do so in multifocal single-system bone involvement. Larger series would be required to confirm this observation. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Juvenile angiofibroma: major and minor complications of preoperative embolization

Introduction: Juvenile angiofibromas (JA) are highly vascular, benign tumours for which surgery is the treatment of choice. In most services, embolisation is performed prior to resection. Nevertheless, there are few data on the complications of preoperative embolisation for JA. Aim: To describe major and minor complications of preoperative embolisation in a 32-year experience of patients undergoing surgical resection of JA at a tertiary hospital. Methods: Retrospective chart review study of 170 patients who underwent surgical resection of JA at a tertiary hospital between September 1976 and July 2008. Results: All patients were male. Age ranged from 9 to 26 years. Ninety-one patients had no complications after embolisation. Overall, 105 complication events occurred of which four major and 101 minor. Conclusion: In our series, preoperative embolisation for JA produced no irreversible complications and no aesthetic or functional sequelae. The vast majority of complications were transient and amenable to clinical management.

Preoperative 6-min walking distance does not predict pulmonary complications in upper abdominal surgery

Background and objective: Field exercise tests have been increasingly used for pulmonary risk assessment. The 6-min walking distance (6MWD) is a field test commonly employed in clinical practice; however, there is limited evidence supporting its use as a risk assessment method in abdominal surgery. The aim was to assess if the 6MWD can predict the development of post-operative pulmonary complications (PPCs) in patients having upper abdominal surgery (UAS). Methods: This prospective cohort study included 137 consecutive subjects undergoing elective UAS. Subjects performed the 6MWD on the day prior to surgery, and their performance were compared with predicted values of 6MWD (p6MWD) using a previously validated formula. PPCs (including pneumonia, tracheobronchitis, atelectasis with clinical repercussions, bronchospasm and acute respiratory failure) were assessed daily by a pulmonologist blinded to the 6MWD results. 6MWD and p6MWD were compared between subjects who developed PPC (PPC group) and those who did not (no PPC group) using Student's t-test. Results: Ten subjects experienced PPC (7.2%) and no significant difference was observed between the 6MWD obtained in the PPC group and no PPC group (466.0 +/- 97.0 m vs 485.3 +/- 107.1 m; P = 0.57, respectively). There was also no significant difference observed between groups for the p6MWD (100.7 +/- 29.1% vs 90.6 -/+ 20.9%; P > 0.05). Conclusions: The results of the present study suggest that the 6-min walking test is not a useful tool to identify subjects with increased risk of developing PPC following UAS.

Comparative Analysis of the Complications of 5347 Endomyocardial Biopsies Applied to Patients After Heart Transplantation and With Cardiomyopathies: A Single-center Study

Introduction. Endomyocardial biopsy (EMB) plays an important role in allograft surveillance to screen an acute rejection episode after heart transplantation (HT), to diagnose an unknown cause of cardiomyopathies (CMP) or to reveal a cardiac tumor. However, the procedure is not risk free. Objective. The main objective of this research was to describe our experience with EMB during the last 33 years comparing surgical risk between FIT versus no-HT patients. Method. We analyzed retrospectively the data of 5347 EMBs performed from 1978 to 2011 (33 years). For surveillance of acute rejection episodes after HT we performed 3564 (66.7%), whereas 1777 (33.2%) for CMP diagnosis, and 6 (1.0%) for cardiac tumor identification. Results. The main complications due to EMB were divided into 2 groups to facilitate analysis: major complications associated with potential death risk, and minor complications. The variables that showed a significant difference in the HT group were as follows: tricuspid Injury (.0490) and coronary fistula (.0000). Among the no-HT cohort they were insufficient fragment (.0000), major complications (.0000) and total complications (.0000). Conclusions. EMB can be accomplished with a low risk of complications and high effectiveness to diagnose CMP and rejection after HT. However, the risk is great among patients with CMP due to their anatomic characteristics. Children also constitute a risk group for EMB due to their small size in addition to the heart disease. The risk of injury to the tricuspid valve was higher among the HT group.

Antiparasitical chemotherapy in Chagas' disease cardiomyopathy: current evidence

Chronic chagasic cardiomyopathy affects 20% of Chagas disease patients. At present, Chagas disease chemotherapy uses nitrofurans, benznidazole (Rochagan (R), Rodanil (R), Roche) or nifurtimox (Lampit (R), Bayer). Treatment during acute and recent chronic phases in childhood effects 71.5% and 57.6%, respectively, of parasitological cure. However, in clinical trials during the late chronic phase, only 5.9% of parasitological cure were achieved. This review focuses on the benefit from aetiological treatment to avoid, stop or revert myocarditis. Divergent data gathered from clinical practice are not convincing to support prescription of aetiological treatment as routine for indeterminate and cardiac chronic patients.

Complications of misdiagnosis of maxillary canine ectopic eruption

Ectopic eruption of maxillary canines can be associated with root resorption of adjacent teeth. This case report describes and discusses an interesting case of a 15-year-old girl with a Class III malocclusion and an impacted maxillary canine. Because of the unfavorable position of the ectopic canine and the severe root resorption of the maxillary left central and lateral incisors, the treatment options included extraction of the maxillary permanent canines. The mandibular first premolars were extracted to compensate for the Class III malocclusion. A panoramic radiograph taken earlier in the mixed dentition already indicated a possible eruption disturbance of the maxillary left permanent canine. The importance of early diagnosis of maxillary canine ectopic eruption is highlighted in this case report. The early identification of radiographic signs of an ectopic pathway of eruption should be followed by deciduous canine extraction to prevent canine retention and maxillary incisor root resorption. (Am J Orthod Dentofacial Orthop 2012;142:256-63)

Keratocystic odontogenic tumors and Carnoy's solution: results and complications assessment

Oral Diseases (2012) 18, 548557 Objective: Keratocystic odontogenic tumors (KOTs) can be treated with Carnoys solution, although this treatment modality is not free from complications. It is important to verify the incidence of complications after the use of Carnoys solution and compare these with the literature. Materials and methods: This study verified the effects of a complementary treatment for KOTs and assessed the incidence of such complications as recurrence, infection, sequestrum formation, mandibular fracture, dehiscence, and neuropathy. Results: Twenty-two KOTs treated with Carnoys solution combined with peripheral ostectomy were included, and the follow-up period varied from 12 to 78 months with a mean of 42.9 months. Complications included recurrence (4.5%), dehiscence (22.7%), infection (4.5%), and paresthesia (18.2%). No difference was found among lesions associated (9.1%) or not (0%) with nevoid basal cell carcinoma syndrome (P > 0.05). Dehiscence was influenced by marsupialization (P < 0.05), and paresthesia was observed exclusively in cases of mandibular canal fenestration (P < 0.01). Conclusions: Complementary treatment with Carnoys solution and peripheral ostectomy appear to provide efficient treatment for KOTs. Complications originating from the use of the solution are less frequent and less serious than complications associated with cryotherapy. Neuropathy seems to be related to direct contact between the solution and the epineurium.