Development of functional biomaterials with micro‐ and nanoscale technologies for tissue engineering and drug delivery applications

Micro‐ and nanotechnologies have emerged as potentially effective fabrication tools for addressing the challenges faced in tissue engineering and drug delivery. The ability to control and manipulate polymeric biomaterials at the micron and nanometre scale with these fabrication techniques has allowed for the creation of controlled cellular environments, engineering of functional tissues and development of better drug delivery systems. In tissue engineering, micro‐ and nanotechnologies have enabled the recapitulation of the micro‐ and nanoscale detail of the cell's environment through controlling the surface chemistry and topography of materials, generating 3D cellular scaffolds and regulating cell–cell interactions. Furthermore, these technologies have led to advances in high‐throughput screening (HTS), enabling rapid and efficient discovery of a library of materials and screening of drugs that induce cell‐specific responses. In drug delivery, controlling the size and geometry of drug carriers with micro‐ and nanotechnologies have allowed for the modulation of parametres such as bioavailability, pharmacodynamics and cell‐specific targeting. In this review, we introduce recent developments in micro‐ and nanoscale engineering of polymeric biomaterials, with an emphasis on lithographic techniques, and present an overview of their applications in tissue engineering, HTS and drug delivery. Copyright © 2012 John Wiley & Sons, Ltd.     

Assessment and Investigation on the Fate of Organochlorine Pesticides in Water and Sediments of International Amir-kalaye Wetland in North of Iran

A total of 48 water samples and 24 sediment samples were collected at four sampling stations along the wetland during four seasons from 2009 to 2010 and analyzed by gas chromatograph–electron capture detector (GC–ECD). In water the total concentration of OCPs was 0.33, 0.01, 0.1 and 0.07 mg/L in summer, autumn, winter and spring, respectively. The most frequent OCP compounds detected were endrin and chlordane (0.08 and 0.07 mg/L), heaxachlorobenzene and chlordane (0.06, 0.02 mg/L), and chlordane (0.07 mg/L) in summer, winter and spring, respectively. The maximum concentration of ΣOCPs was found in samples collected from station 1 in summer (0.26 mg/L). In sediments the total concentrations of OCPs were 15.84 and 2.62 mg/g-dry weight (dw) in summer and winter, respectively. Chlordane was the most frequently found OCP compound, followed by lindane, 9.92 and 2.47 mg/g-dry weight (dw), respectively, in summer. While, lindane (2.52 mg/g-dw) and endosulfan I (0.1 mg/g-dw) were the highest OCP compounds detected in winter. The results obtained in this study show that there still exist a variety of organochlorine pesticide residues in the water and sediments from the Amir-kalaye wetland in Iran.     

Interferon-beta in pediatric multiple sclerosis patients: safety in short-term prescription

None of the approved immunomodulatory drugs in adults Multiple Sclerosis (MS) patients have been officially approved for the pediatric patients and are currently used off-label in this population. In this study, we evaluated the effectiveness and tolerability of intramuscular interferon beta1-a (Avonex(?)) and subcutaneously injected interferon beta1-b (Betaferon(?)) in children with definite relapsing-remitting MS (RRMS). Thirteen patients aged younger than 16, who were recently diagnosed with definite RRMS according to the McDonald's criteria, were enrolled in this study. Six patients were treated with Avonex(?) 30 μg, intramuscularly every week, and seven patients were treated with Betaferon(?) 250 μg, subcutaneously every other day. All patients were treated with adult doses; initially interferon-beta was prescribed with half dose, and it was increased to full adult dose steadily. Eleven girls and two boys, mean (SD) age of 14.7 (1.9) years, were studied. Following nine months of using interferon-beta, nine patients (69.2%) had no relapses and the remaining four, experienced only one relapse. The mean EDSS score was decreased significantly after the study period. The present study provides reasonable data for the use of interferon-beta in Pediatric MS due to lack of short-term complications and safety. Studies with larger sample size and longer follow up duration are required to shed light on the long term impact of the interferon-beta therapy in children.     

Comparing cystatin C changes as a measure of renal function before and after radiotherapy in patients with stomach cancer

The objective of this study was to determine and compare cystatin C changes before and after radiotherapy in patients with stomach cancer who were candidate for radiotherapy. This study was conducted as a prospective cohort one. Eighteen patients with definite diagnosis of stomach cancer under treatment by radiotherapy who presented to Radiotherapy-Oncology Center of Imam Hossein Hospital, Tehran-Iran, and the treatment in all cases was simultaneous chemoradiation with Xeloda were included. In all patients before radiotherapy and after radiotherapy serum creatinine (Cr) and cystatin C were measured simultaneously. Mean cystatin level before treatment (1.2 ± 0.4) was significantly lower than that of post-treatment (1.6 ± 0.36), (P=0.001). Serum Cr level before treatment was 1.15 ± 0.33 and after radiotherapy was 1.08 ± 0.24 and did not show significant difference. Glomerular filtration rate (GFR) of the patients before radiotherapy was -46.8 ± 21.0 and after radiotherapy was 43.8 ± 15.8 that did not have significant difference (P=0.146) and also blood urea nitrogen (BUN) before radiotherapy was 20.72 ± 3.7 and 20 ± 6.38 after radiotherapy that did not have significant difference (P=0.6). Comparison of the cystatin C difference with total radiation dose of the kidneys that are put in three dose groups in radiotherapy field had association that in dose of less that 18 gray (Gy) the cystatin C change showed significant and positive association (P=0.027; r=0.52) and about 18-24 Gy the cystatin C difference showed significant and negative association (P=0.023, r=-0.53). It seems that for evaluating the renal function, serum cystatin C measurement is preferable than serum Cr. level.     

Improving Adult Immunization Practices Using a Team Approach in the Primary Care Setting

Objectives. The objective of this study was to improve the immunization rates of primary care practices using a team approach.Methods. Practices performed 35 random chart abstractions at 2 time points and completed a survey about immunizations at baseline and 12 months after intervention. Data were collected for the following immunizations: influenza, pneumococcal, tetanus diphtheria (Td)/tetanus diphtheria pertussis (Tdap), hepatitis A, hepatitis B, meningococcal, varicella, herpes zoster, and human papilloma virus. Between baseline and after intervention, practice teams were given feedback reports and access to an online educational tool, and attended quality improvement coaching conference calls.Results. Statistically significant improvements were seen for Td/Tdap (45.6% pre-intervention, 55.0% post-intervention; P ≤ .01), herpes zoster (12.3% pre-intervention, 19.3% post-intervention; P ≤ .01), and pneumococcal (52.2% pre-intervention, 74.5% post-intervention; P ≤ .01) immunizations. Data also revealed an increase in the number of physicians who discussed herpes zoster and pneumococcal vaccinations with their patients (23.2% pre-intervention, 43.3% post-intervention; P ≤ .01 and 19.9% pre-intervention, 43.0% post-intervention; P ≤ .01, respectively) as well as an increase in physicians using the Centers for Disease Control and Prevention immunization schedule (52.9% pre-intervention, 88.2% post-intervention; P ≤ .02).Conclusions. The immunization rates of the primary care practices involved in this study improved.The need for improving quality is pervasive in the primary care setting, involving physicians, their practice teams, and administrative staff. The issue of low quality is well documented1–3 and is not partial to any 1 disease condition.4–15 Poor quality is a result of our medical system’s orientation to the urgent, its focus on acute and not chronic care, lack of adherence to evidence-based guidelines, and an increasing number of patients with complex medical conditions.2 Quality is characterized as a systems issue rather than an individual one,16 which has led efforts to focus on the practice team. Practice teams have been shown to improve quality in primary care.17,18 The issues with poor quality in primary care extend to the practice of adult immunizations.19 It is estimated that between 50 000 and 70 000 US adults die each year because of diseases that could be prevented by vaccination.20 For example, influenza is the sixth leading cause of death for adults and contributes to at least 200 000 hospitalizations and 36 000 deaths annually.21,22 Economic costs associated with influenza are projected to be $87.1 billion.23Adult vaccination guidelines, such as those published by the Centers for Disease Control and Prevention (CDC) and Advisory Committee on Immunization Practices,24 are increasingly evidence-based and are a good reference for practices to measure themselves against when doing immunization practice redesign work. Although childhood vaccinations have become a public health success, adult vaccination rates are low, prompting the movement toward “lifespan immunizations.”20,25 However, quality gaps and missed opportunities for vaccination exist between the number of patients who are recommended to receive vaccinations and those who actually receive them.26–30 A variety of barriers at the practice, patient, economic, and social level help explain these missed opportunities. For instance, only 60% of physicians reported using CDC and Advisory Committee on Immunization Practice guidelines as their reference for adult immunizations, and most often reported recommending vaccinations at well visits compared with sick visits.31 Physicians also reported multiple barriers to vaccinating patients, including lack of health insurance, fear of needles, and misconception of the safety and efficacy of vaccinations.31 In turn, patients consistently reported that their physicians do not recommend vaccinations.31,32A comprehensive quality approach was considered to be more effective than mere guideline dissemination because the latter has not been shown to be successful alone in changing practice patterns.33,34 The American College of Physicians (ACP) developed this quality improvement program to help physicians and practice teams learn about the current recommendations and best practices for adult immunization. The goal of this prospective study was to improve the immunization practices of primary care practices by using a team approach.     

An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge

One limitation in the development of an improved cellular response needed for an effective HIV-vaccine is the inability to induce robust effector T-cells capable of suppressing a heterologous challenge. To improve cellular immune responses, we examined the ability of an optimized DNA vaccine to boost the cellular immune responses induced by a highly immunogenic Ad5 prime. Five Chinese rhesus macaques received pVax encoding consensus (con) gag/pol/env intramuscularly (IM) with electroporation followed by the Merck Ad5 gag/pol/nef vaccine. A second group of five animals were vaccinated with Merck Ad5 gag/pol/nef followed by pVax gag/pol/env. One year following vaccination, Ad5-prime DNA-boosted monkeys and four unvaccinated controls received an intrarectal challenge with 1000 ID50 SIV(mac)251. The quality and magnitude of the T-cell response was analyzed by ELISpot and polyfunctional flow cytometry. We observed that an Ad5-prime DNA-boost resulted in significantly elevated SIV-specific T-cell responses even compared with animals receiving a DNA-prime Ad5-boost. Ad5 prime DNA boosted animals were capable of suppressing a pathogenic SIV(mac)251 challenge. Peak control correlated with the expansion of HLA-DR(+) CD8(+) T-cells two weeks post-infection. These data illustrate that high optimization of a DNA vaccine can drive of immune responses primed by a robust vector system. This previously unachievable feature of these newly optimized DNAs warrants future studies of this strategy that may circumvent issues of serology associated with viral vector prime-boost systems.     

Liposomal SLA co-incorporated with PO CpG ODNs or PS CpG ODNs induce the same protection against the murine model of leishmaniasis

First generation Leishmania vaccines consisting of whole killed parasites with or without adjuvants have reached phase 3 trial and failed to show enough efficacy mainly due to the lack of an appropriate adjuvant. In this study, the nuclease-resistant phosphorothioate CpG oligodeoxynucleotides (PS CpG) or nuclease-sensitive phosphodiester CpG ODNs (PO CpG) were used as adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Due to the susceptibility of PO CpG to nuclease degradation, an efficient liposomal delivery system was developed to protect them from degradation. 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid was used because of its unique adjuvanticity and electrostatic interaction with negatively charged CpG ODNs. To evaluate the role of liposomal formulation in protection rate and enhanced immune response, BALB/c mice were immunized subcutaneously with liposomal soluble Leishmania antigens (SLA) co-incorporated with PO CpG (Lip-SLA-PO CpG), Lip-SLA-PS CpG, SLA+PO CpG, SLA+PS CpG, SLA or buffer. As criteria for protection, footpad swelling at the site of challenge, parasite loads, the levels of IFN-γ and IL-4, and the IgG subtypes were evaluated. The groups of mice receiving Lip-SLA-PO CpG or Lip-SLA-PS CpG showed a high protection rate compared with the control groups. In addition, there was no significant difference in immune response generation between mice immunized with PS CpG and the group receiving PO CpG when incorporated into the liposomes. The results suggested that liposomal form of PO CpG might be used instead of PS CpG in future vaccine formulations as an efficient adjuvant.     

Natural analcime zeolite modified with 2,3,5,6-tetra(2-pyridyl)pyrazine for preconcentration and determination of trace amounts of cadmium by flame atomic absorption spectrometry

An analytical method using natural analcime zeolite modified with tppz (2,3,5,6-tetra-pyridylpyrazine) for preconcentration of cadmium, in a column system, and their sequential determination by flame atomic absorption spectrometry (FAAS), was developed. In this work, cadmium was adsorbed onto natural analcime zeolite modified with tppz and then was recovered by nitric acid. Solutions of cadmium were passed through a glass column packed with 100?mg of the sorbent material, at pH 5.0, and cadmium was eluted with 2.0?M HNO(3) at a flow rate of 2.0?ml?min(-1). The relative standard deviation (RSD) for eight replicate determinations at the 2.5?μg of cadmium was ±0.94%. The calibration curve using the preconcentration system was linear from 0.01 to 4?μg?ml(-1) in final solution with a correlation coefficient of 0.9993. This method was successfully applied for the determination of cadmium in various samples.