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Mechanical test methods for biomedical membranes.

It is important to estimate the mechanical characteristics and strength of biomedical membrane. For this purpose, previously we have proposed several mechanical test methods for biomedical membranes. To establish the safety design for biomedical membrane, such as cellophane membrane for hemodialysis, it is important to estimate the viscoelastic characteristics of these materials. On the other hand, artificial biomedical membrane such as tympanic membrane, are subjected to noncontact internal air pressure under the membranous state. To estimate mechanical characteristics of such membrane, it is necessary to develop a well-simulated test under the gaseous pressure and the other mechanical test under the membranous state. In this paper, several test methods for these purposes were shown. Furthermore, results obtained by these methods were shown and related to clinical problems. These proposed test methods are quite different from the axial tensile test. But they are also important to estimate the mechanical property of biomedical membrane. Each result obtained by these test methods has its own significance. By selection of the most suitable test method for each purpose and revealing these mutual relations, safety design of artificial organs can be performed from the viewpoint of the strength.

Cellophane↗

Stimulation of islet cell proliferation enhances pancreatic ductal carcinogenesis in the hamster model.

Previous studies have shown that some N-nitrosobis (2-oxopropyl)amine (BOP)-induced ductal/ductular pancreatic cancers in the hamster model develop within islets and that streptozotocin (SZ) pretreatment that caused islet degeneration and atrophy inhibits pancreatic cancer induction. Hence, it appears that in this model islets play a significant role in exocrine pancreatic carcinogenesis. To examine whether stimulation of islet cell proliferation (nesidioblastosis) enhances pancreatic exocrine cancer development, we tested the effect of the pancreatic carcinogen BOP in hamsters after induction of nesidioblastosis by cellophane wrapping. Before wrapping, hamsters were treated with SZ to inhibit pancreatic tumor induction in the unwrapped pancreatic tissues. Control groups with a wrapped pancreas did not receive SZ. Six weeks after SZ treatment, all hamsters were treated with BOP (10 mg/kg body weight) weekly for 10 weeks and the experiment was terminated 38 weeks after the last BOP treatment. Many animals recovered from their diabetes at the time when BOP was injected and many more after BOP treatment. Only nine hamsters remained diabetic until the end of the experiment. Both SZ-treated and control groups developed proliferative and malignant pancreatic ductal-type lesions primarily in the wrapped area (47%) but less frequently in the larger segments of the pancreas, including the splenic lobe (34%), gastric lobe (13%), and duodenal lobe (6%). Only a few lesions developed in the unwrapped pancreatic region of nine diabetic hamsters with atrophic islets, whereas seven of these hamsters had tumors in the wrapped area. Histologically, most tumors appeared to originate from islets, many invasive carcinomas had foci of islets, and some tumor cells showed reactivity with anti-insulin. The results show that, in the BOP hamster model, islets are the site of formation of the major fraction of exocrine pancreatic cancer and that induction of nesidioblastosis enhances pancreatic carcinogenesis.

Animals↗

Psychological stress perturbs epidermal permeability barrier homeostasis: implications for the pathogenesis of stress-associated skin disorders.

BACKGROUND: A large number of skin diseases, including atopic dermatitis and psoriasis, appear to be precipitated or exacerbated by psychological stress. Nevertheless, the specific pathogenic role of psychological stress remains unknown. In 3 different murine models of psychological stress, it was recently shown that psychological stress negatively impacts cutaneous permeability barrier function and that coadministration of tranquilizers blocks this stress-induced deterioration in barrier function. OBJECTIVES AND METHODS: The relationship between psychological stress and epidermal permeability barrier function was investigated in 27 medical, dental, and pharmacy students without coexistent skin disease. Their psychological state was assessed with 2 well-validated measures: the Perceived Stress Scale and the Profile of Mood States. Barrier function was assessed simultaneously with the stress measures at periods of presumed higher stress (during final examinations) and at 2 assumed, lower stress occasions (after return from winter vacation [approximately 4 weeks before final examinations] and during spring vacation [approximately 4 weeks after final examinations]). RESULTS: The subjects as a group demonstrated a decline in permeability barrier recovery kinetics after barrier disruption by cellophane tape stripping, in parallel with an increase in perceived psychological stress during the higher vs the initial lower stress occasions. During the follow-up, presumed lower stress period, the subjects again displayed lower perceived psychological stress scores and improved permeability barrier recovery kinetics, comparable to those during the initial lower stress period. Moreover, the greatest deterioration in barrier function occurred in those subjects who demonstrated the largest increases in perceived psychological stress. CONCLUSION: These studies provide the first link between psychological status and cutaneous function in humans and suggest a new pathophysiological paradigm, ie, stress-induced derangements in epidermal function as precipitators of inflammatory dermatoses.

Adult↗

Lamellar macular hole: a complication of cystoid macular edema after cataract extraction.

A woman developed an inner lamellar macular hole and cellophane maculopathy as a complication of chronic cystoid macular edema following cataract extraction. Fluorescein angiography revealed a cystoid pattern of fluorescence in the paracentral area but no evidence of staining in the region of the hole. Following death, histopathologic examination of both eyes confirmed the clinical observations. Biomicroscopic examination and fluorescein angiography are of value in differentiating an inner lamellar macular hole from a full-thickness macular hole and from a pseudomacular hole caused by spontaneous contraction of an epiretinal membrane.

Cataract Extraction↗

Human massive periretinal proliferation. In vitro characteristics of cellular components.

The sources of cellular constituents of fibrous and cellophane membranes formed in massive periretinal proliferation have been unclear. We successfully obtained cellular outgrowths from abnormal vitreous specimens collected at surgery for massive periretinal proliferation in 13 patients, using standard culture techniques. By phase-contrast and ultrastructural morphological criteria, we identified four major cellular constituents: (1) macrophages present in all specimens: (2) pigmented epithelioid cells, present in a majority of specimens; (3) glial-like cells, present in a majority of specimens; and (4) fibroblastic cells, present in all specimens but much more prominent in grossly fibrous tissues. Our findings confirm published reports of pigmented epithelioid cells and glial-like cells in fixed surgical specimens and advance our understanding of the heterogeneity of pathologic cells active in producing this serious complication of retinal reattachment surgery.

Adolescent↗

Development, differentiation, and regeneration potential of the Vervet monkey endocrine pancreas.

Using immunolabelling techniques, characterization of the Vervet monkey pancreas included a study of both its development and its structure and normal functioning in the adult. We found that PP and somatostatin occurred during development before glucagon. Insulin and all four pancreatic peptides occurred in one of the primordial buds prior to fusion. These finding call into question the suggested contribution of only PP cells by the ventral bud and non-PP cells by the dorsal bud. Co-localization of glucagon and PP was observed extensively with their relative expressions occurring in what appeared to be an organised non-random manner. Cells expressing both glucagon and PP persisted in the adult, together with many other combinations, suggesting an interesting plasticity of endocrine cell differentiation in the adult. Cellophane wrapping of the head of the Vervet monkey pancreas was shown to result in a noticeable increase in duct cell proliferation and endocrine cell volume but no increased replication of endocrine cells. Cells, immunoreactive for pancreatic peptides, were observed to bud from the ducts, suggesting a regeneration of endocrine cell tissue by neogenesis, although it is uncertain whether the duct epithelium contains the only stem cell source of new endocrine tissue. Hopefully, further investigations will elucidate a mechanism by which endocrine cell regenerative capacity can be stimulated in diabetics to overcome their absolute or relative deficiencies of insulin production.

Animals↗

Low voltage isoelectric focusing for the study of red cell acid phosphatase polymorphism: improved phenotyping and better agreement with the Hardy Weinberg distribution.

A low voltage isoelectric focusing (IEF) method for typing human red cell acid phosphatase (ACPl) polymorphism is reported. A clear differentiation of the ACPl*A, ACPl*B and ACPl*C allelic products is obtained by minimizing diffusion of the bands during electrophoresis and during enzyme visualization by using a hydrophilic cellophane film soaked with the substrate solution, heated to 50 degrees C, and by reading without incubation in a moist chamber. A population study of ACPl, carried out with this method, on a sample of 624 unrelated individuals of the population of Rome (gene frequencies: ACPl*A = 0.267; ACPl*B = 0.680; ACPl*C = 0.053), showed a good agreement between the observed and expected phenotype distribution (chi 2/2 = 1.35; 0.70 greater than p greater than 0.50).

Acid Phosphatase↗

High resolution density gradient electrophoresis of cellular organelles.

A density gradient electrophoresis apparatus made of Perspex was constructed, with a separation column (7 x 2.2 cm) containing a 0-5% linear Ficoll gradient. The useful separation path is 6 cm. A specially designed gradient mixer is described which fits over the application cone. This cone permits precise gradient and sample introduction as well as undisturbed fractionation after electrophoresis. A bottom circular palladium cathode is separated hydrodynamically but not electrically from the density gradient by a cellophane membrane, merely secured by an O-ring. The top circular platinum anode allows for upward electrophoresis (80-100 min at 10 mA). The markedly higher resolution of subcellular organelles was compared with separations obtained earlier with a small, but much more difficult to fabricate, prototype. Moreover, ease of manipulation was greatly improved. A wide separation distance was obtained between plasma membrane, endoplasmatic reticulum as well as between two populations of lysosomes. Even early, middle, and late endosomes could be separated with high resolution. Soluble isoenzymes could be separated as well and were far away from the vesicle-enclosed enzymes.

Cellulose↗

Detrimental effect of visible light on meiosis of mammalian eggs in vitro.

Short wavelength visible light (less than 470-480 nm) emmitted from ordinary light sources is detrimental to unfertilized hamster eggs in that prolonged exposure to the light disturbs the completion of normal meiosis after the eggs are penetrated by spermatozoa. The fluorescent light commonly used in modern laboratories is more harmful than the light from incandescent lamps. In experiments involving the handling of eggs in vitro, minimal exposure to the light or the use of appropriate filters (e.g., red cellophane sheets) is recommended.

Animals↗

Hermetic packaging of drugs: optimized sealing of foil pouches.

Factors affecting the sealing of foil packages were studied in the sealing of foil packages were studied in three laboratories. The relationship of sealing temperature (with machine speed and pressure kept constant) to the incidence of defective packages was determined. The maximum acceptable limit for defective pouches was 1%. Three tests were employed to detect defects: vacuum-dye, seal strength, and pressurized ammonia vapor. Only the last was sensitive enough to determine the optimum sealing conditions. This test also was capable of detecting leakage sites. Replacement of the cellophane layer of the foil laminate with polyvinylidene chloride-coated polyester improved the barrier properties of the package.

Ammonia↗

Physical model evaluation of topical prodrug delivery--simultaneous transport and bioconversion of vidarabine-5'-valerate III: Permeability differences of vidarabine and n-pentanol in components of hairless mouse skin.

The permeation behavior of 3H-vidarabine (3H-9-beta-D-ara-binofuranosyladenine) and 14C-n-pentanol through different strata of hairless mouse skin was studied using a diffusion cell at 37 degrees under steady-state conditions. Partition coefficients for the skin components verus 0.9% aqueous NaCl solution also were obtained. Various skin preparations including full-thickness skin, cellophane-stripped skin, and dermis membranes of different thicknesses were employed. The dermis membranes were considered to be diffusionally homogenous, and the product of the permeability coefficient and the thickness was taken as the apparent diffusivity. The apparent diffusivities for both compounds investigated were independent of thickness. Therefore, it was concluded that the molecular diffusivity is constant throughout the dermis. Comparisons of permeability coefficients in various strata of the skin revealed that, while the stratum corneum is the major diffusional barrier, the epidermis appears to be significantly less permeable than the dermis.

Administration, Topical↗

Physical model evaluation of topical prodrug delivery--simultaneous transport and bioconversion of vidarabine-5'-valerate V: Mechanistic analysis of influence of nonhomogeneous enzyme distributions in hairless mouse skin.

The mathematical problem of simultaneous transport and metabolism in the case of nonuniform enzyme distributions in the skin was solved, and the solutions were used for analyzing experimental data. Experimental data were obtained from permeation experiments with 3H-vidarabine and its 5'-valerate using cellophane tape-stripped hairless mouse skin. Results of the analyses revealed that the esterase activity was four to nine times higher in the epidermis than in the dermis, whereas the deaminase activity was about the same in the two strata. These results were in good agreement with independent experiments using tissue homogenates. The enzyme distributions and the previously reported diffusivities were employed in generating concentration profiles for the prodrug and the drug in the skin. These results may be used in predicting the possible therapeutic effect of the prodrug when it is topically applied.

Administration, Topical↗

Medicament release from suppository bases I: Physicochemical characteristics and bioavailability of indomethacin in rabbits.

This investigation was designed to determine the in vitro release of indomethacin from suppository bases and the in vivo bioavailability in rabbits. Suppositories containing 25 mg of indomethacin were made by the fusion method with theobroma oil, esterified fatty acids (C10-C18), and polyethylene glycol 1000. To produce an exact dosage form, a formula for the determination of the displacement value was derived, and it was found that theobroma oil greater than esterified fatty acids (C10-C18) greater than polyethylene glycol 1000. The suppository hardness was determined by using appropriate apparatus and it was found that the esterified fatty acids (C10-C18) allowed the formation of more brittle suppositories. The release rates were determined with the USP dissolution apparatus, with or without cellophane membrane, and it was found that polyethylene glycol 1000 greater than esterified fatty acids (C10-C18) greater than theobroma oil. The bioavailability of indomethacin after rectal administration was greater with polyethylene glycol base. Significant correlation was obtained during the first 45 min between the in vitro release (dialyzing tubing) and the in vivo bioavailability.

Animals↗

Methods for in vitro percutaneous absorption studies V: Permeation through damaged skin.

The permeation of compounds through skin damaged by different methods was compared because agents that are absorbed through skin are sometimes applied to a damaged barrier. The removal of the stratum corneum by stripping the skin with cellophane tape was the most effective method for enhancing absorption. A minimal increase in water permeation was obtained when one abrasion line was made with a hypodermic needle, but the absorption increased substantially when three to six lines were made across the site of application. Similar values were obtained with in vivo and in vitro techniques for penetration of cortisone and nicotinic acid through normal and abraded rat skin. Sever damage by UV irradiation to rats in vivo resulted in nicotinic acid absorption similar to that obtained in vitro through abraded or tape-stripped skin. Damage from mild irradiation could not be accurately duplicated by in vitro methods. The magnitude of the increase in absorption of seven chemicals through abraded human and rat skin was related to the extent to which the molecules were absorbed by the skin. The greatest increases in penetration were obtained with the compounds that were most poorly absorbed.

Animals↗

In vivo percutaneous penetration of some organic compounds related to anatomic site in humans: predictive assessment by the stripping method.

The effect of anatomic site on the in vivo relationship between the total penetration of four compounds and the amount of the compounds present in the stratum corneum at the end of application was studied in humans. For each anatomic site, 1,000 nmol of 14C-radiolabeled benzoic acid, benzoic acid sodium salt, caffeine, or acetylsalicylic acid was applied to 1-cm2 area of skin of male Caucasian patients aged 28 +/- 2 years (groups of 6-8). For each molecule and each site, a first application on the right-hand side of the body allowed total absorption to be determined by measuring the amount excreted in the urine. A second application, performed 48 h later on the contralateral site, enabled the total amount of substance present in the stratum corneum at the end of application (30 min) to be assessed after cellophane-tape stripping of the treated area. The results showed that skin permeability varied substantially, depending both on the physicochemical nature of the molecule and on the anatomical location. In general, the rank order in skin permeability of the studied areas appears to be as follows: arm less than or equal to abdomen less than postauricular less than forehead. Whatever the compound applied, the forehead was approximately 2 times as permeable as the arm or abdomen. Independent of the origin of the differences in permeability observed among sites, there exists a linear correlation (r = 0.97, p less than 0.001) between the amounts of substance present in the stratum corneum at the end of application (30 min) and the total amounts which penetrated within a 4-d period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Factors affecting iontophoretic mobility of metoprolol.

The effect of different factors on the iontophoretic transport of metoprolol was analyzed. In vitro experiments were first performed in a diffusion cell with a cellophane membrane. Comparison of different pH, buffers, and ionic strengths in the donor compartment showed that higher iontophoretic transport was obtained with phthalate buffer (0.01 M) at pH 3. When the current density increased, the flux of metoprolol also increased. A decrease in drug concentration or an increase in viscosity slowed down the iontophoretic transport of metoprolol. The fluxes of metoprolol through hairless rat skin were strongly enhanced compared with passive diffusion. Direct current seemed to be more efficient than pulse current. When the on:off ratio of the pulse current was reduced, the flux also decreased.

Algorithms↗

Transdermal iontophoresis and solute penetration across excised human skin.

The potential of transdermal iontophoresis to facilitate drug delivery was evaluated by studying the transport kinetics of model compounds salicylate (anion), phenylethylamine (cation), mannitol (polar neutral compound of low molecular weight), and inulin (polar neutral compound of high molecular weight) using an excised human skin model. The transport kinetics of solutes were determined across both intact and cellophane-tape-stripped dermatomed skin both in the presence and absence of applied current to probe the mechanisms of iontophoretic delivery. Iontophoresis effectively enhanced delivery of all compounds relative to passive transport. The skin is shown to be both ion selective and size selective. On the basis of results from present work and other studies, the "aqueous pathway" of iontophoretic transport is further reinforced.

Administration, Cutaneous↗

An overview of polylactides as packaging materials.

Polylactide polymers have gained enormous attention as a replacement for conventional synthetic packaging materials in the last decade. By being truly biodegradable, derived from renewable resources and by providing consumers with extra end-use benefits such as avoiding paying the "green tax" in Germany or meeting environmental regulations in Japan, polylactides (PLAs) are a growing alternative as a packaging material for demanding markets. The aim of this paper is to review the production techniques for PLAs, summarize the main properties of PLA and to delineate the main advantages and disadvantages of PLA as a polymeric packaging material. PLA films have better ultraviolet light barrier properties than low density polyethylene (LDPE), but they are slightly worse than those of cellophane, polystyrene (PS) and poly(ethylene terephthalate) (PET). PLA films have mechanical properties comparable to those of PET and better than those of PS. PLA also has lower melting and glass transition temperatures than PET and PS. The glass transition temperature of PLA changes with time. Humidity between 10 and 95% and storage temperatures of 5 to 40 degrees C do not have an effect on the transition temperature of PLA, which can be explained by its low water sorption values (i.e. <100 ppm at Aw = 1). PLA seals well at temperatures below the melting temperature but an appreciable shrinking of the films has been noted when the material is sealed near its melting temperature. Solubility parameter predictions indicate that PLA will interact with nitrogen compounds, anhydrides and some alcohols and that it will not interact with aromatic hydrocarbons, ketones, esters, sulfur compounds or water. The CO2, O2 and water permeability coefficients of PLA are lower than those of PS and higher than those of PET. Its barrier to ethyl acetate and D-limonene is comparable to PET. The amount of lactic acid and its derivatives that migrate to food simulant solutions from PLA is much lower than any of the current average dietary lactic acid intake values allowed by several governmental agencies. Thus, PLA is safe for use in fabricating articles for contact with food.

Biocompatible Materials↗