Polymer colon drug delivery systems and their application to peptides, proteins, and nucleic acids

Most therapeutic peptides and proteins are administered via the parenteral route, which presents numerous drawbacks and limitations. To overcome these drawbacks, alternative administration routes, such as oral or mucosal routes, have been investigated. The oral route presents a series of attractive advantages for the administration of therapeutic compounds, such as the avoidance of the pain and discomfort associated with injections, good patient compliance, and being less expensive to produce. However, oral administration of peptides, proteins, or nucleic acids also presents several difficulties because of their instability in the upper gastrointestinal (GI) tract and their poor transport across biologic membranes. Among the various approaches developed to improve the oral delivery of peptides, proteins, or nucleic acids, specific delivery to the colon has attracted a lot of interest because of its potential for the local treatment of colonic diseases, systemic delivery of poorly absorbed drugs, and vaccine delivery. Numerous pharmaceutical approaches described in this review have been exploited for the development of colon-targeted drug delivery systems using various concepts, such as pH-dependent, time-dependent, pressure-controlled, or bacterially triggered delivery systems. The action of the pH-dependent delivery systems is based on pH differences between the stomach and the ileum. Time-dependent delivery systems are based on the transit time of pharmaceutical dosage forms in the GI tract, drug release being delayed until they reach the colon. A combination of pH- and time-dependent delivery systems has also been described to avoid the drawbacks of both strategies. The pressure-controlled delivery concept exploits the physiologic luminal pressure of the colon as the driving force for site-specific delivery of drugs. Finally, bacterially triggered delivery systems exploit the enormous diversity of enzymatic activity associated with the colonic microflora. Bacterially triggered delivery systems are generally composed of polymers, which are specifically degraded by colonic enzymes of microbial origin. These polymers have been used to form prodrugs with the drug moiety, as coating materials for the drug core, or as embedding media to entrap the drug into matrix or hydrogel systems. Each of these concepts has advantages and limitations. They present varied colonic specificity and, among them, bacterially triggered delivery systems in particular show the greatest potential for colonic delivery of peptides, proteins, and nucleic acids.     

Metabolism of 2-phenylethylamine and phenylacetaldehyde by precision-cut guinea pig fresh liver slices.

2-Phenylethylamine is an endogenous constituent of human brain and is implicated in cerebral transmission. It is also found in certain foodstuffs and may cause toxic side-effects in susceptible individuals. Metabolism of 2-phenylethylamine to phenylacetaldehyde is catalyzed by monoamine oxidase and the oxidation of the reactive aldehyde to its acid derivative is catalyzed mainly by aldehyde dehydrogenase and perhaps aldehyde oxidase, with xanthine oxidase having minimal transformation. The present investigation examines the metabolism of 2-phenylethylamine to phenylacetaldehyde in liver slices and compares the relative contribution of aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase activity in the oxidation of phenylacetaldehyde with precision-cut fresh liver slices in the presence/absence of specific inhibitors of each enzyme. In liver slices, phenylacetaldehyde was rapidly converted to phenylacetic acid. Phenylacetic acid was the main metabolite of 2-phenylethylamine, via the intermediate phenylacetaldehyde. Phenylacetic acid formation was completely inhibited by disulfiram (specific inhibitor of aldehyde dehydrogenase), whereas isovanillin (specific inhibitor of aldehyde oxidase) inhibited acid formation to a lesser extent and allopurinol (specific inhibitor of xanthine oxidase) had little or no effect. Therefore, in liver slices, phenylacetaldehyde is rapidly oxidized by aldehyde dehydrogenase and aldehyde oxidase with little or no contribution from xanthine oxidase.     

Medial cortex strain distribution during noncemented total hip arthroplasty

Intraoperative proximal femur fractures are a significant concern during noncemented total hip arthroplasty. The current study was performed to investigate the hypothesis that broaching the femur and inserting the stem without using mallet applied impact loads will reduce the risk of intraoperative fracture. Rosette strain gauges were applied to the medial and anteromedial cortex of six human anatomic specimen femurs to compare the strain distribution for broaching and stem insertion. Eight additional femurs were used to compare the strain distribution for stem insertion using impact loading and constant rate stem insertion. For the impact loading stem insertions, the soft tissues surrounding the femur were modeled. Constant rate stem insertions were performed using a mechanical testing machine. The largest strains measured at the medial and anteromedial sites primarily were aligned with the femur hoop axis. The largest strain magnitude, orientation, and sign (tensile or compressive) varied widely among femurs. The stem insertion strains were significantly larger than the broaching strains (two-way analysis of variance with replication). The impact stem insertion strains were not significantly different from the constant rate stem insertion strains. The results indicate that the femur geometry and material properties have a greater influence on the strain distribution than does the implantation technique.     

Ophthalmoscopic contact lenses for transpupillary thermotherapy

Ophthalmoscopic contact lenses for transpupillary thermotherapy (TTT) must provide effective visualization of retinal treatment sites and transmission of infrared diode laser radiation. Selection and proper use of retinal laser lenses requires knowledge of their lateral magnification, laser beam magnification factor, field of view and resolution. Optical performance is analyzed for Goldmann-type lenses and a series of inverted image lenses of differing magnification. Goldmann lenses have the highest resolution, but inverted image lenses of comparable magnification have 2.5 times or more their field of view. Inverted image lenses of similar magnification can differ in resolution. They require 2-4% more incident laser power to produce the same retinal irradiance as a Goldmann lens, but this difference is small in comparison to other clinical variables. Tilting an ophthalmoscopic contact lens up to 15° causes little distortion in the circularity of the retinal spot formed by a laser beam or difference in retinal irradiance across the spot. Inverted image lenses produce higher anterior segment irradiances than Goldmann-type lenses, but anterior segment injuries are less likely in TTT than conventional visible light, short-pulse retinal photocoagulation because of the comparatively low irradiances used in TTT and the decreased absorption of diode laser infrared radiation in ocular media and melanin.     

Protein‐energy intakes in a malnourished population after increasing the supply of the dietary staples

This paper examines the extent to which food intake in malnourished populations is affected by increasing the availability of the dietary staples. Free amounts of corn and beans were supplied to 47 families in a rural Guatemalan community during eight weeks. Relative to a six‐week baseline period, adults increased their intakes by about 400 kcal (1.68 MJ) and 15 gof protein per day. The average changes for pre‐school children were 198 kcl (0.83 MJ) and 5.8 g of protein per day. The findings suggest that it is possible for adults to satisfy their energy and protein needs by consuming more corn and beans. In children, bulk may be a limiting factor and it may be necessary to resort to additional measures, such as increasing the energy density of the diet, to satisfy needs.     

qMRI relaxometry of mandibular bone marrow: A monomodal distribution in sickle cell disease

Purpose:

To identify and characterize sickle cell disease (SCD)‐related changes in the composition of mandibular bone marrow using qMRI relaxometry histograms.

Materials and Methods:

Thirteen SCD patients and 17 controls underwent brain MR imaging with the mixed turbo spin‐echo (TSE) pulse sequence at 1.5T. The mandible was manually segmented and divided into body, angle, ramus, and condyle. T1 and T2 histograms of each mandible were modeled with Gaussian functions. The relaxation time histogram peaks were calculated, and the number of monomodal versus bimodal curves was compared.

Results:

SCD patients exhibited monomodal distributions on both T1 and T2 histograms, consistent with a composition of predominantly red hematopoietic marrow. Eighty‐eight percent of mandibles in control subjects exhibited a bimodal distribution in T1 and all showed a bimodal distribution in T2, indicating mixed but predominantly yellow marrow composition. The second peak in control subjects was shorter in T1 and longer in T2, consistent with yellow marrow composition.

Conclusion:

Instead of physiological fatty replacement, SCD patients exhibit red marrow persistence in the mandible, likely due to the increased demand for hematopoiesis. This phenomenon can be manifested by a monomodal curve in both T1 and T2 relaxometric histograms. J. Magn. Reson. Imaging 2013;37:1182–1188. © 2012 Wiley Periodicals, Inc.     

Pesticides as risk factors for head and neck cancer: A review

Humans may be exposed to pesticides such as fungicides, herbicides, and insecticides, during occupational and non‐occupational activities. Pesticides could be related to cancer development mainly because of their effects on the endocrine and immune systems and their cumulative effect. The present review evaluated in current literature evidence of an association between exposure to pesticides and the occurrence of head and neck cancer (HNC). A literature search for cohort studies was conducted in the PubMed, Web of science, and Cochrane databases. Methodological quality of each study was rated with the Scottish Intercollegiate Guidelines Network (SIGN) checklist. One thousand one hundred and thirty‐two studies were identified. Thirty‐two were included. Most of the studies found addressed occupational exposure to pesticides and were conducted in Europe and North America. Eleven high‐quality studies were found. Most of them found no association between exposure to pesticides and increased risk of HNC. Two studies found some evidence of a positive association between pesticide (malathion and atrazine) exposure and thyroid cancer. The literature review does not support a clear evidence for association between pesticides exposure and HNC. Only limited evidence points to a positive association between exposure to some pesticides and thyroid cancer. Further standardized studies based on appropriate designs are required to clarify the effect of pesticides on the genesis of HNC, considering dose, length of exposure, and type of pesticide.