Wound pH-Responsive Sustained Release of Therapeutics from a Poly(NIPAAm-co-AAc) Hydrogel

Wound pH strongly influences residence time and activity of various growth factors during wound healing. Hence, a pH-responsive sustained release growth factor delivery system could be beneficial for effective treatment of wound. In this context, an effort was made to evaluate the potential of a poly(N-isopropylacrylamide-co-acrylic acid) hydrogel as pH-sensitive sustained release system for wound-pH-dependent therapeutics delivery. The polymer was synthesized via radical copolymerization and influence of pH on lower critical solution temperature (LCST), microarchitechture and swelling of the hydrogel was evaluated. Results showed a pH-dependent variation in the physical properties of the hydrogel within the wound pH range. Fluorescence recovery after photobleaching (FRAP) analysis endorsed a pH dependent restricted diffusion of the BSA in the hydrogel. Later, release of bovine serum albumin (BSA), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) (each 5%, w/v) from the hydrogel within the range of wound pH (pH 6.7–7.9) were examined. Analysis showed non-Fickian release of therapeutics from the hydrogel with a significant variation in release rate and cumulative release with the increase in pH. Retention of the bioactivity of the released EGF was confirmed by studying murine dermal fibroblast cell proliferation in vitro. Finally, a growth factor (EGF or VEGF)-loaded hydrogel was applied on a murine excisional wound model and showed augmentation of wound healing in comparison to conventional sustained release growth factor therapy.     

Synthesis and Characterization of Zwitterionic Co-polymers as Matrices for Sustained Metoprolol Tartrate Delivery

Very stable co-polymer (vinyl acetate (VA)-co-3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) (p(VA-co-DMAPS)) latexes with different compositions have been synthesized by emulsifier-free emulsion co-polymerization. The dry p(VA-co-DMAPS)s have been used in the preparation of drug tablets for sustained Metoprolol tartrate release. It has been shown that the tablet swelling depends on the mol fraction of DMAPS monomer units (m _DMAPS), pH and ionic strength (I). An original explanation, based on the swelling behavior of p(VA-co-DMAPS), has been proposed for the "overshooting" phenomenon observed. It assumes the formation of hydrophilic domains with a higher m _DMAPS in the co-polymer tablets. The formation of dipole–dipole clusters between the DMAPS units at different m _DMAPS and I are the main cause for the established differences in both the swelling kinetics of the p(VA-co-DMAPS) matrices and Metoprolol tartrate release. The obtained results show that for p(VA-co-DMAPS) matrices-based tablets controlled sustained Metoprolol tartrate release can be realized just by varying two parameters, co-polymer composition and I.     

Novel Degradable Co-polymers of Polypyrrole Support Cell Proliferation and Enhance Neurite Out-Growth with Electrical Stimulation

Synthetic polymers such as polypyrrole (PPy) are gaining significance in neural studies because of their conductive properties. We evaluated two novel biodegradable block co-polymers of PPy with poly(ε-caprolactone) (PCL) and poly(ethyl cyanoacrylate) (PECA) for nerve regeneration applications. PPy–PCL and PPy–PECA co-polymers can be processed from solvent-based colloidal dispersions and have essentially the same or greater conductivity (32 S/cm for PPy–PCL, 19 S/cm for PPy–PECA) compared to the PPy homo-polymer (22 S/cm). The PPy portions of the co-polymers permit electrical stimulation whereas the PCL or PECA blocks enable degradation by hydrolysis. For in vitro tests, films were prepared on polycarbonate sheets by air brushing layers of dispersions and pressing the films. We characterized the films for hydrolytic degradation, electrical conductivity, cell proliferation and neurite extension. The co-polymers were sufficient to carry out electrical stimulation of cells without the requirement of a metallic conductor underneath the co-polymer film. In vitro electrical stimulation of PPy–PCL significantly increased the number of PC12 cells bearing neurites compared to unstimulated PPy–PCL. For in vivo experiments, the PPy co-polymers were coated onto the inner walls of nerve guidance channels (NGCs) made of the commercially available non-conducting biodegradable polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV). The NGCs were implanted in a 10 mm defect made in the sciatic nerve of rats, and harvested after 8 weeks. Histological staining showed axonal growth. The studies indicated that these new conducting degradable biomaterials have good biocompatibility and support proliferation and growth of PC12 cells in vitro (with and without electrical stimulation) and neurons in vivo (without electrical stimulation).     

盐酸恩丹西酮缓释片的研制及体外释药特性

制备盐酸恩丹西酮缓释片并对影响释药的因素进行考察。以羟丙甲纤维素（HPMC）为骨架材料制备了盐酸恩丹西酮缓释片，通过正交设计试验优选最佳处方和工艺。对影响释药的因素，如HPMC的黏度和用量、填充剂的种类、制片工艺、润湿剂及释放介质pH等进行了考察。盐酸恩丹西酮缓释片体外释药符合Higuchi方程，HPMC的黏度、填充剂的种类及测定释放度的转速对该缓释片的释药几乎无影响，而制片工艺、润湿剂及释放介质pH值对缓释片释药影响较大。盐酸恩丹西酮缓释片在体外12h缓释效果较好。     

Synthesis and Characterization of CREKA-Targeted Polymers for the Disruption of Fibrin Gel Matrix Propagation

Recently, efforts to control the propagation of the fibrin gel matrix (FGM) are under investigation as a means of limiting the formation of post-surgical adhesions (PSAs). A series of polymeric biomaterials based on block co-polymers of methacrylic acid (MA) and methoxypolyethylene glycol methacrylate (PEGMA) have been synthesized and characterized in order to study the impact of molecular architecture on the performance of these materials in suppressing FGM development. A robust synthetic strategy has been developed to facilitate the well controlled variation of numerous structural properties, including the relative size of each polymer block, the total polymer length, and the length of poly(ethylene glycol) (PEG) chain length, and to incorporate the fibrin-targeting pentapeptide cysteine–arginine–glutamic acid–lysine–alanine (CREKA). Preliminary investigations, based on quartz crystal microgravimetry (QCM), indicate the importance of molecular architecture in modulating the FGM propagation from model surfaces.     

Ganglion Cells with Sustained Activity in the Fish Retina and Their Possible Function in Evaluation of Visual Scenes

Neuroscience and Behavioral Physiology - Background extracellular spike activity of single ganglion cells was recorded from axon terminals in the optic tectum of living immobilized fish. The sizes...     

Evaluation of a group intervention for children with food allergy and their parents

BACKGROUND: Children with food allergy and their parents may experience substantial stress related to the risk of serious reactions and the demands of allergy management. OBJECTIVE: To evaluate a group intervention for children with food allergy and their parents designed to increase parent-perceived competence in coping with food allergy and to decrease the parent-perceived burden associated with food allergy. METHODS: Sixty-one children aged 5 to 7 years with food allergy and their parents attended 1 of 4 half-day workshops, with parent and child groups run concurrently. Parents completed self-report measures of perceived competence in coping with food allergy at 3 time points: preworkshop (within 8 weeks of the intervention), postworkshop (immediately after the intervention), and follow-up (4-8 weeks after the intervention). Parents completed a measure of burden associated with food allergy at preworkshop and follow-up. Parents and children also completed evaluations of the study intervention. RESULTS: Parent-perceived competence in coping with food allergy increased significantly from preworkshop to postworkshop and follow-up, and parent-perceived burden associated with food allergy decreased from preworkshop to follow-up. Parent and child evaluations of the workshop were favorable. CONCLUSIONs: These findings provide preliminary support for the effectiveness and feasibility of a group intervention for children with food allergy and their parents and suggest the importance of controlled evaluations of group interventions in this population in the future.     

Evaluation of a psychoeducation program for Chinese clients with schizophrenia and their family caregivers

Objectives

To evaluate the effectiveness of a psychoeducation program for Chinese clients with schizophrenia and their family caregivers.

Methods

A randomized controlled trial was conducted. Seventy-three clients with a diagnosis of schizophrenia and their caregivers (n = 73) were recruited and randomized into a study (n = 36) and control group (n = 37). Ten psychoeducation sessions were provided to the study group. The outcomes were measured at the baseline, immediately after (post-1), six months (post-2), and 12 months after the intervention (post-3).

Results

There were significant treatment effects across time for all client outcomes: adherence to medication (p < 0.01), mental status (p < 0.01), and insight into illness (p < 0.01). However, no significant differences were found between groups at the post-3 measures for all client outcomes. For the caregivers, significant group differences were only detected in self-efficacy at the post-1 (p = 0.007) and post-2 (p < 0.001) measures, the level of satisfaction at the post-1 (p = 0.033) and post-2 (p < 0.021) measures, and the perception of family burden at the post-2 measures (p = 0.043).

Conclusion

A psychoeducation intervention had positive effects on Chinese clients and their caregivers. However, these effects might not be sustained 12 months after the intervention.

Practice implications

To substantiate its effects, psychoeducation should be an ongoing intervention, with its outcomes constantly evaluated.     

Evaluation of a program for the pharmacologic management of children with asthma

An evaluation of a program used for the pharmacologic management of asthma was conducted by a retrospective chart review of patients seen by the Pediatric Allergy and Pulmonary Service at the University of Iowa. A scheme for drug selection based on pharmacologic and physiologic principles had been used to determine the medication requirements needed to attain specified therapeutic goals. Explicit criteria, defined prior to the review, were used to confirm the diagnosis, characterize the patients as chronically or intermittently symptomatic, and grade the disease by severity prior to the initiation of therapy. Of the 25 patients with intermittent symptoms, none of the patients with the 2 least severe grades of asthma required more than as-needed bronchodilators for control of symptoms while 80% of the patients in the 2 more severe grades required corticosteroids (p = 0.002). Among the 172 patients with chronic symptoms, a single noncorticosteroid prophylactic drug (usually theophylline in optimal doses) was the final management requirement for nearly 90% of the 27 patients in the 2 least severe grades of chronic asthma, for 70% of 129 patients in grade III, and in only 30% of the 16 patients in grade IV, the most severe grade (p < 0.001). This method for evaluating a pharmacologic management program has implications both for physician education and identification of patients used in drug trials.     

Synthesis of Monodisperse Polymer Microspheres with Mercapto Groups and Their Application as a Stabilizer for Gold Metallic Colloid

Summary: Monodisperse polymer microspheres with functional mercapto groups on the surface were prepared from poly[(ethylene glycol dimethacrylate)‐co‐(2‐hydroxyethyl methacrylate)], poly(EGDMA‐co‐HEMA), microspheres successively through esterification of the active hydroxyl groups with acryloyl chloride to introduce carbon‐carbon double bonds and then the addition reaction of hydrogen sulfide to the double bond at pH 10–11. All of the polymer microspheres were characterized by scanning electron microscopy (SEM) and FT‐IR spectra. The mercapto‐functionalized polymer microspheres were utilized as a stabilizer for gold metallic colloids through coordination of the mercapto group on the polymer with gold metallic nanoparticles, which were prepared by the reduction of gold chloride trihydrate with sodium borohydride as the reductant. The size and morphology of the gold on the microspheres were determined to be of narrow dispersity (in the range 4–8 nm) by transmission electron microscopy (TEM).

Preparation of mercapto‐modified polymer microspheres and their application as a stabilizer for gold metallic colloids.     

Evaluation of a patient with both aquagenic and cholinergic urticaria

An 11-yr-old girl presented with a history of urticaria induced by warm or cool showers, exercise, and emotional stimuli. During evaluation she repeatedly developed generalized punctate urticaria, pruritus, palpitations, and headaches after warm baths or exercise, and she had a positive methacholine skin test. She developed similar lesions and pruritus after local application of sterile water, tap water, ethanol, normal saline, or 3% saline. The diagnosis of combined aquagenic and cholinergic urticaria was made and presented a unique opportunity to study and compare mediator release and clinical symptoms in both conditions. The patient was submerged in bath water at either 37° or 41° C to induce either aquagenic or cholinergic urticaria, respectively. Histamine was released into the systemic circulation in both condition in a similar time course; however, systemic symptoms occurred only after the 41° C bath. After failure to induce tolerance to the 41° C bath water, hydroxyzine therapy was instituted. One week later she was rechallenged; few symptoms appeared, and a rise in serum histamine was not detected as had been shown in previous challenges. The data suggest that in our patient, hydroxyzine may have contributed to the inhibition of both histamine release and the appearance of symptoms during hot bath challenging.     

Rational Design and Evaluation of a Multiepitope Chimeric Fusion Protein with the Potential for Leprosy Diagnosis

Despite the reduction in the number of leprosy cases registered worldwide as a result of the widespread use of multidrug therapy, the number of new cases detected each year remains stable in many countries. This indicates that Mycobacterium leprae, the causative agent of leprosy, is still being transmitted and that, without an earlier diagnosis, transmission will continue and infection will remain a health problem. The current means of diagnosis of leprosy is based on the appearance of clinical symptoms, which in many cases occur after significant and irreversible nerve damage has occurred. Our recent work identified several recombinant antigens that are specifically recognized by leprosy patients. The goal of the present study was to produce and validate the reactivity of a chimeric fusion protein that possesses the antibody binding properties of several of these proteins. The availability of such a chimeric fusion protein will simplify future test development and reduce production costs. We first identified the antibody binding regions within our top five antigen candidates by performing enzyme-linked immunosorbent assays with overlapping peptides representing the amino acid sequences of each protein. Having identified these regions, we generated a fusion construct of these components (protein advances diagnostic of leprosy [PADL]) and demonstrated that the PADL protein retains the antibody reactivity of the component antigens. PADL was able to complement a protein that we previously produced (the leprosy IDRI [Infectious Disease Research Institute] diagnostic 1 [LID-1] protein) to permit the improved diagnosis of multibacillary leprosy and that had a good ability to discriminate patients with multibacillary leprosy from control individuals. A serological diagnostic test consisting of these antigens could be applied within leprosy control programs to reduce transmission and to limit the appearance of leprosy-associated disabilities and stigmatizing deformities by directing treatment.Leprosy is a devastating disease caused by infection with the bacterium Mycobacterium leprae. The clinical symptoms, underlying immunological responses, bacterial burden, and pathology vary widely between individuals. In 1966, Ridley and Jopling proposed a now widely used classification scheme that allows reasonable consistency in clinical and research practice by dividing the leprosy spectrum into five parts (18). Patients with the true tuberculoid (TT) form of leprosy present with few skin lesions and little nerve damage, granulomas that are histologically similar to those found in tuberculosis, and a T-helper-1-skewed immune response such that very few, if any, bacteria can be detected in biopsy specimens. At the other end of the spectrum, patients with the lepromatous leprosy (LL) form present with multiple skin lesions and a loss of sensation caused by nerve damage. Patients with LL leprosy have diffuse rather than well-organized granulomas mainly consisting of foamy macrophage influxes, and the immune response is biased toward a T-helper-2 type of response. Consequently, large numbers of bacteria and high antibody titers to components of M. leprae can be observed in LL patients. The borderline tuberculoid (BT), the borderline borderline (BB), and borderline lepromatous (BL) forms are distinguishable between the polar extremes of the TT and LL forms, according to the number lesions and the organization of the granuloma (22).Leprosy is typically classified on the basis of clinical manifestations and skin smear results. Simple guidelines have been suggested by the World Health Organization (WHO), with diagnostic criteria listed as being one or more of the following: hypopigmented or reddish skin patches with a definite loss of sensation, thickened peripheral nerves, and the appearance of acid-fast bacilli on analysis of skin smears and biopsy specimens (25a). In the classification based on skin smears, patients showing negative smears with samples from all sites are grouped as having paucibacillary (PB) leprosy, while those showing positive smears with samples from any site are grouped as having multibacillary (MB) leprosy. In practice, however, because skin-smear services are absent or unreliable, most programs use clinical criteria to classify individual patients and select their treatment regimens. The clinical system uses the number of skin lesions and the number of nerves involved to group leprosy patients into one of two simplified categories: MB leprosy (five or more lesions) and PB leprosy (less than five lesions). Thus, TT patients and most BT patients are categorized as having PB leprosy, while LL, BL, BB, and some BT patients are categorized as having MB leprosy.Leprosy treatment involves a prolonged regimen of antibiotics in the form of multidrug therapy (MDT). For MB leprosy, a combination therapy employing rifampin, dapsone, and clofazimine is recommended for 12 months, while for PB leprosy a regimen with only rifampin and dapsone given over 6 months is recommended. It is particularly important to ensure that patients with MB disease are not undertreated with the regimen for the PB form of the disease. Thus, determination of an appropriate treatment regimen requires the accurate and differential diagnosis of the MB and PB forms.A rapid, easy-to-use test that would simplify leprosy diagnosis could greatly assist with the prompt initiation of treatment. Tests based on IgM recognition of phenolic glycolipid I (PGL-I) have been used in a confirmatory role in the clinic (3, 4, 6, 14, 19, 20, 26). Testing for the presence of PGL-I-specific IgM gives a fairly high false-positive rate (>10%) in areas where leprosy is endemic, and while positive responses are indicated to be risk factors in the development of disease, the fact that many people with antibodies against PGL-I do not develop leprosy has hindered the widespread adoption of these tests in screening programs (4, 5, 14). For these reasons, additional antigens have been produced by our group and others with the goal of providing a clear, accurate, and rapid means of diagnosis of leprosy (8, 9, 15, 23).In the study described here, we have extended our previous observations by creating a new polyepitope chimeric fusion protein with the potential to bind to serum antibodies of leprosy patients to provide a leprosy diagnosis. We refined our previous observations by determining antibody-reactive regions within select antigens in order to produce a synthetic protein that combines these reactive portions within a single product. Our results indicate that all portions contained within the synthetic protein retain their antibody binding activity and that this protein has utility for leprosy diagnosis.     

Evaluation of a new point-of-care test for influenza A and B virus in travellers with influenza-like symptoms

Point-of-care (POC) tests for influenza facilitate clinical case management, and might also be helpful in the care of travellers who are at special risk for influenza infection. To evaluate influenza POC testing in travellers, a new assay, the ImmunoCard STAT! Flu A and B, was used to investigate travellers presenting with influenza-like symptoms. Influenza virus infection was diagnosed in 27 (13%) of 203 patients by influenza virus-specific PCR and viral culture. The POC test had sensitivity and specificity values of 64% and 99% for influenza A, and 67% and 100% for influenza B, respectively. Combined sensitivity and specificity were 67% and 99%, respectively, yielding positive and negative predictive values of 95%, and positive and negative likelihood ratios of 117 and 0.34, respectively. The convenient application, excellent specificity and high positive likelihood ratio of the POC test allowed rapid identification of influenza cases. However, negative test results might require confirmation by other methods because of limitations in sensitivity. Overall, influenza POC testing appeared to be a useful tool for the management of travellers with influenza-like symptoms.     

Evaluation of a voluntary, military-style residential treatment program for adolescents with academic and conduct problems.

This study evaluated the effectiveness of a military-style residential treatment program for adolescents with academic and conduct problems. Two hundred twelve referred adolescents were separated into 3 groups for analyses: (a) adolescents who completed the 22-week program, (b) adolescents who prematurely withdrew, and (c) wait-list controls. Adolescents' socioemotional and behavioral functioning were measured at baseline and 6 months after treatment. Results showed statistically and clinically significant reductions in externalizing symptoms and increases in adaptive behavior associated with treatment. Treatment was also associated with increased likelihood of high school completion or employment and decreased likelihood of alcohol or drug problems and arrest. The relation between treatment participation and outcomes was moderated by adolescents' living environments after treatment, but it was not moderated by age of symptom onset. The benefits of treatment may be partially attributable to the voluntary nature of the intervention.     

Development and Evaluation of a Loop-mediated Isothermal Amplification Combined with Au-nanoprobe Assay for Rapid Detection of Mycobacterium tuberculosis

Loop-mediated isothermal amplification (LAMP) has been proposed as an inexpensive and easy to perform assay for molecular diagnostics. We present a novel strategy for the detection of LAMP amplicons derived from Mycobacterium tuberculosis by the use of Au-nanoprobes. When applied to a total of 93 clinical specimens, the LAMP assay demonstrated sensitivity and specificity higher than that of polymerase chain reaction and culture. The Au-nanoprobe augmented LAMP test platform with its advantages of robust reagents and a simple colorimetric detection method can be adapted easily for the rapid detection of other infectious disease agents at a low cost.     

Evaluation of a structured pharmacist-led inhalation technique assessment service for patients with asthma and COPD in Norwegian pharmacies

Objective

To investigate whether the inhalation technique improved among patients with asthma and chronic obstructive pulmonary disease after an Inhalation Technique Assessment Service (ITAS), and to assess the patients’ and pharmacists’ perceptions of ITAS.

Evaluation of a semi-automated Seegene PCR workflow with MTB,MDR, and NTM detection for rapid screening of tuberculosis in a low-prevalence setting

In areas of low tuberculosis (TB) prevalence, laboratory diagnosis of TB may essentially cover non-tuberculous mycobacteria (NTM) in addition to Mycobacterium tuberculosis (MTB). In this study, a semi-automated PCR workflow distinguishing MTB and NTM (Anyplex™ MTB/NTMe, Seegene) and subsequently detecting MTB isoniazid/rifampicin resistance (Allplex™ MTB/MDRe, Seegene) was evaluated for replacing smear microscopy of acid-fast bacilli as the rapid screening method for TB. With 279 clinical samples, 47 cultures positive for MTB and 76 for NTM, the Anyplex™ MTB/NTMe assay and smear microscopy showed equal sensitivities (49.6% vs 50.8%, respectively) but Anyplex™ MTB/NTMe was more sensitive for MTB (63.8% vs 25.6%) than for NTM (40.8% vs 64.5%). Allplex™ MTB/MDRe showed a slightly higher sensitivity of 68.1% for MTB (32/47 positive, n = 222). Antibiotic resistance profiles were correctly identified for all MTB isolates (one MDR isolate). Specificity was 100% for both assays. Anyplex™ MTB/NTMe detected all the 18 NTM species present in the study. The analytical performance of the evaluated high-throughput workflow was relatively weak compared to culture but potentially adequate as a rapid screening method analogous to smear microscopy with additional differentiation between TB, MDR-TB, and NTM.