Journal of Toxicology-cutaneous and Ocular Toxicology最新文献

{"title":"Nutraceuticals: the link between nutrition and medicine","authors":"H. Biesalski","doi":"10.1081/CUS-120004324","DOIUrl":"https://doi.org/10.1081/CUS-120004324","url":null,"abstract":"Nutrition science during recent decades has been focused on the detection and understanding of deficiencies. With increasing knowledge of the existence and action of vitamins, specific recommendations were given with the aim of avoiding classical deficiency diseases such as xerophthalmia, beriberi, etc. A further step was the epidemiological evidence that diet contributes to the risk of certain diseases. The major finding was the correlation of a high fat intake with several kinds of cancer and cardiovascular disease. The consequences were special lowfat and low-cholesterol foods. However, the increasing knowledge about micronutrients including vitamins, minerals, and further compounds (carotenoids, flavonoids, anthocyans, etc.) on a molecular level together with results from epidemiological studies opens a new and exciting field of nutrition science, nutraceuticals (NC), as a link between nutrition and medicine. Nutraceutical is a term coined in 1979 by Stephen DeFelice (1). According to DeFelice, it is defined “as a food or parts of food, that provide medical or health benefits, including the prevention and treatment of disease.” Subsequently, several other terms (medical food, functional food, nutritional supplements) were used. Nutraceuticals may range from isolated nutrients, dietary supplements, and diets to genetically engineered “designer” foods, herbal products, and processed products, such as cereals, soups, and beverages. The increasing interest in nutraceuticals reflects the fact that consumers hear about epidemiological studies","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"20 1","pages":"30 - 9"},"PeriodicalIF":0.0,"publicationDate":"2001-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90767097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo methods for percutaneous absorption measurements","authors":"R. Wester, H. Maibach","doi":"10.1081/CUS-120001866","DOIUrl":"https://doi.org/10.1081/CUS-120001866","url":null,"abstract":"There is a persistent belief that skin viability has little importance in percutaneous absorption. This concept of skin as a passive membrane has led to the domination of the study of percutaneous absorption by laws of mass action and physical diffusion. This concept has also led investigators to use skin excised from cadavers (human and animal) and then to physically (e.g., by freezing or heat separation) and chemically isolate skin sheets or sections and determine chemical diffusion across these treated tissues. A recent study shows that these methods destroy skin viability (1). Human skin viability currently can be maintained for up to a week under the proper conditions. A consequence of this earlier concept was the designation of the stratum corneum as the barrier to percutaneous absorption. Many compounds such as low-molecular-weight alcohols were studied, and the barrier properties of the isolated stratum corneum were demonstrated for these chemicals. It has then been assumed that the stratum corneum is the primary barrier for all compounds. The need to study percutaneous absorption has its reality in dermatotoxicity, by which compounds pose a threat to human health, and in dermatopharmacology, for which drugs need to be delivered into and through the skin to treat disease both locally (skin disease) and systemically (transdermal delivery). Most compounds and defined drugs that are of interest and concern in dermatotoxicology and dermatopharmacology are lipophilic.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"1 1","pages":"411 - 422"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85161619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mathematical models in percutaneous absorption","authors":"M. Roberts, Y. Anissimov, Richard A. Gonsalvez","doi":"10.1081/CUS-120001859","DOIUrl":"https://doi.org/10.1081/CUS-120001859","url":null,"abstract":"A number of mathematical models have been used to describe percutaneous absorption kinetics. In general, most of these models have used either diffusion-based or compartmental equations. The object of any mathematical model is to a) be able to represent the processes associated with absorption accurately, b) be able to describe/summarize experimental data with parametric equations or moments, and c) predict kinetics under varying conditions. However, in describing the processes involved, some developed models often suffer from being of too complex a form to be practically useful. In this chapter, we attempt to approach the issue of mathematical modeling in percutaneous absorption from four perspectives. These are to a) describe simple practical models, b) provide an overview of the more complex models, c) summarize some of the more important/useful models used to date, and d) examine sonic practical applications of the models. The range of processes involved in percutaneous absorption and considered in developing the mathematical models in this chapter is shown in Fig. 1. We initially address in vitro skin diffusion models and consider a) constant donor concentration and receptor conditions, b) the corresponding flux, donor, skin, and receptor amount-time profiles for solutions, and c) amount- and flux-time profiles when the donor phase is removed. More complex issues, such as finite-volume donor phase, finite-volume receptor phase, the presence of an efflux. rate constant at the membrane-receptor interphase, and two-layer diffusion, are then considered. We then look at specific models and issues concerned with a) release from topical products, b) use of compartmental models as alternatives to diffusion models, c) concentration-dependent absorption, d) modeling of skin metabolism, e) role of solute-skin-vehicle interactions, f) effects of vehicle loss, a) shunt transport, and h) in vivo diffusion, compartmental, physiological, and deconvolution models. We conclude by examining topics such as a) deep tissue penetration, b) pharmacodynamics, c) iontophoresis, d) sonophoresis, and e) pitfalls in modeling.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"14 1","pages":"221 - 270"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80237543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DERMAL TOXICITY OF LINEAR ALKYLBENZENE SULPHONATE AND NICKEL IN GUINEA PIGS","authors":"A. Mathur, R. Shanker","doi":"10.1081/CUS-100000337","DOIUrl":"https://doi.org/10.1081/CUS-100000337","url":null,"abstract":"Guinea pigs were dermally exposed to linear alkylbenzene sulphonate (LAS) or nickel or in combination. In general, lipid peroxidation, histamine contents, acid phosphatase, β-glucuronidase, alkaline phosphatase, and glutathione-S-transferase showed elevations when exposed simultaneously to LAS and Ni. The Ni contents also increased in the skin. Histologically the skin revealed more hyperkeratinization and degenerative changes when it was exposed simultaneously to LAS and Ni.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"5 1","pages":"23 - 27"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84628510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental stressors and the eye","authors":"J. Trevithick, K. Mitton","doi":"10.1081/CUS-120001854","DOIUrl":"https://doi.org/10.1081/CUS-120001854","url":null,"abstract":"Of all our senses, the most valued is sight. The eye, by virtue of its function in vision, must be in contact with the external environment. The cornea admits light, which is fine-focused by the lens into images and passes through aqueous and vitreous humors before reaching the retina. All of the component parts of the eye are susceptible to environmental stresses, depending on whether direct or indirect effects are involved, because of its external exposure. Indirect effects can arise when, for instance, one component of the eye influences another, either by (1) damaging lipid peroxides originating in the degenerating retina, causing damage to the lens posterior (1–4); or (2) immune damage to the lens via the aqueous humor from plasma antibodies to lens proteins (5). Direct effects can occur when toxic substances or physical trauma contact the eye surface, damaging the cornea. Penetrating wounds can damage the lens epithelium, and chemicals in the environment can diffuse across the cornea and aqueous humors to damage the lens epithelium or trabecular meshwork. Unfortunately, medications necessary for serious medical conditions, such as steroidal anti-inflammatory drugs, can have damaging side effects on the lens or cause a harmful elevation in intraocular pressure. Nutritional influences can also be very important, potentiating in severe deficiencies causing damage to the cornea, lens, or retina.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"33 1","pages":"71 - 88"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85379842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AN IN VITRO MODEL OF OXIDATIVE STRESS AND HYPOXIA IN RETINAL PIGMENTED EPITHELIAL CELLS","authors":"M. Palmero, J. Bellot, C. García-Cabanes, A. Orts","doi":"10.1081/CUS-100000339","DOIUrl":"https://doi.org/10.1081/CUS-100000339","url":null,"abstract":"Retinal pigmented epithelium (RPE) is an ocular tissue that performs a variety of functions including metabolism of photoreceptors. It constitutes an electrical and chemical barrier regulating the movement of solutes and ions between neural retina and the choriocapillary network. Reactive oxygen intermediate (ROI) generation has been implicated in the etiology of certain neurodegenerative diseases of the eye, which may be positively altered by treatment with antioxidant drugs. Cell viability under oxidative stress, hypoxia, and ischemic conditions in RPE were studied in vascular epithelium (VE) cells in culture to explore the possible role of vitamin C and N-acetyl-cysteine to prevent cell injury. The results of this study show that RPE cells may be protected against free radicals and products of peroxidation by endogenous scavengers by treatment with antioxidant drugs.","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"52 1","pages":"39 - 47"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77209423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of molecular transport across human stratum corneum in vivo","authors":"A. Naik, Y. Kalia, F. Pirot, R. Guy","doi":"10.1081/CUS-120001861","DOIUrl":"https://doi.org/10.1081/CUS-120001861","url":null,"abstract":"A percutaneously delivered therapeutic agent, whether directed at the systemic circulation or the local tissues, must traverse the stratum corneum (SC), which effectively restricts molecular transport between the external environment and the interior of the human body. The composition of the SC, and the highly tortuous nature of the extracellular pathway (1), makes this relatively thin biomembrane perhaps the body’s most efficient barrier. This has been a great boon to the transdermal formulation scientist, who can effortlessly evaluate transcutaneous drug transport by relatively uncomplicated in vitro diffusion experiments using excised or “simulated” skin. These experiments have been, and remain, instrumental to the preliminary screening of transdermal candidates, formulation excipients, and in mechanistic assessments, but, as with all methodology, present a number of obvious limitations, which collectively generate a cogent argument for human in vivo evaluations in many situations. First, the SC unfortunately lacks the consistent performance desirable of most synthetic rate-determining membranes in that its barrier properties vary both","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"26 1","pages":"279 - 301"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89667300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of ocular free radicals in age-related macular degeneration","authors":"P. Bernstein, Nikita B. Katz","doi":"10.1081/CUS-120001856","DOIUrl":"https://doi.org/10.1081/CUS-120001856","url":null,"abstract":"Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the western world, is a major ocular public health problem of increasing concern, especially in light of the world’s rapidly growing elderly population. It is a particularly frustrating disease for ophthalmologists and their patients due to its relentless progressive course, which can ultimately lead to legal blindness. For the vast majority of patients, there are no proven interventions that can halt or reverse the damage wrought by the disease. Since treatment options in the late stages of AMD are so limited, there is considerable interest in identifying modifiable environmental risk factors that in turn could be used to guide early intervention strategies to lessen the risk of visual loss from AMD in susceptible individuals. As will be discussed below, there is substantial evidence that retinal pathology due to AMD is in part mediated by oxidative damage to photoreceptors and other ocular cells. The possibility that individuals can modulate their risk of visual loss from AMD by decreasing their exposure to environmental oxidants or by increasing their dietary consumption of antioxidants has been enthusiastically embraced by many members of the ophthalmic community, by the nutraceutical industry, and by the general public. The scientific basis to support these interventions, however, often lags behind the popular wisdom. In this chapter, the pathogenesis of AMD will be reviewed, the possible mechanisms for free radical","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"4 1","pages":"141 - 181"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78994564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Routes of exposure: Topical and transdermal","authors":"M. Cukierski, A. Loper","doi":"10.1081/CUS-120001865","DOIUrl":"https://doi.org/10.1081/CUS-120001865","url":null,"abstract":"The dermal route of administration poses a number of scientific, technical, and regulatory challenges to those charged with characterizing the safety of new excipients for topical or transdermal use. Many of these challenges will be discussed in this chapter. The goal of safety testing is the protection of patients from potential harm caused by a new excipient that will be applied to the skin. This chapter highlights scientific, technical, and some regulatory nuances specific to the dermal route of administration for the safety assessment of new pharmaceutical excipients. Reliance on dermal drug-testing strategies, which are not always straightforward, may result in a scope of testing that exceeds that necessary for an excipient. The most difficult aspects of developing a preclinical (nonclinical) toxicology strategy for a new pharmaceutical excipient are (a) to determine if certain testing is necessary or relevant, and (b) to successfully use the results of the toxicology studies to help direct clinical study designs. Recently, the Safety Committee of the International Pharmaceutical Excipients Council (IPEC) published proposed guidelines for the safety testing of new pharmaceutical excipients (1).","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"11 1","pages":"367 - 410"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73620460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood flow as a technology in percutaneous absorption: The assessment of the cutaneous microcirculation by laser Doppler and photoplethysmographic techniques","authors":"E. Tur","doi":"10.1081/CUS-120001869","DOIUrl":"https://doi.org/10.1081/CUS-120001869","url":null,"abstract":"Optical techniques for blood flow measurement were first introduced more than 60 years ago with the innovation of photoplethysmography (1), substantiated and expanded by Hertzman (2). Laser Doppler techniques came forth 40 years later (3), followed by the manufacture of commercial devices (4,5), and consequently photoplethysmography was put aside. These optical methodologies enable tracing of the movement of red blood cells in the skin. This is useful in following percutaneous penetration, when the penetrant has an effect on blood vessels or on blood flow. In addition, physiology and anatomy of the skin can be studied, as well as pathology. Moreover, laser Doppler flowmetry (LDF) measurements are applicable in the evaluation of internal diseases and conditions that affect the skin microvasculature. The diverse application areas of the technique include tissues other than the skin, like the buccal, nasal, or rectal mucosa, as well as the intestine through an endoscope, and kidney, liver, or lung intraoperatively. This chapter exclusively deals with cutaneous laser Doppler flowmetry (LDF) and reviews only investigations where this method was used to measure skin blood flow. In each field of LDF investigation, knowledge has broadened in the last few years. In view","PeriodicalId":17547,"journal":{"name":"Journal of Toxicology-cutaneous and Ocular Toxicology","volume":"48 1","pages":"429 - 459"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79116386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}