By I. Roland. San Jose Christian College. 2018.

Extensive research on the physiological activity of the skin has provided evidence that even small changes in the environment can modify the activity of skin tissue (3 generic v-gel 30 gm free shipping herbals for weight loss,4) 30gm v-gel fast delivery humboldt herbals. As mentioned by Gilchrest, the Food and Drug Administration asked her to define water as a drug, when water was applied on the skin under experimental condi- tions (7). Registration of a product as a drug requires many elaborate and costly procedures; therefore, the manufacturer of a product with pharmaceutical activity would prefer to have the product registered as a cosmetic. This might mean that the pharmaceutical activity of the product is not mentioned and/or investigated, and, as a result of these confusing and old-fashioned regulatory rules, important information is not given to the public. The introduction of the term ‘‘cosmeceutical’’ enables us to classify more precisely a product with an activity that is intended to treat or prevent a (mild) skin (abnormality). In order to avoid introducing new definition criteria, we sug- gest that cosmeceuticals are only regarded as a subclass within the domain of a Definition 11 Table 1 Cosmeceuticals as a Subclass of Cosmetics (Europe and Japan) and as a Subclass of Drugs (U. In Europe and Japan, cosmeceuticals can be regarded as a subclass of cosmetics; however, in the United States cosmeceuticals can only be regarded as a subclass of drugs. Cosmeceuticals could be characterized as fol- lows: (1) The product has pharmaceutical activity and can be used on normal or near-normal skin. The definition of minor skin disorders or mild skin abnormalities is difficult and can be regarded as cosmetic indications. Even socioeconomic factors may have an impact on whether a skin disorder is regarded as a disease or as a cosmetic indication (8,9). Nevertheless, in most western countries there is no written consensus that skin abnormalities that are treated by over-the-counter drugs may be regarded as mild skin disorders or may be termed cosmetic indications (9,10). The procedure for registration of a cosmeceutical should not be as cumber- some as for drugs. The intended activity of the cosmeceutical for treatment of a minor skin disorder should be demonstrated by clinical studies within the frame- work of good clinical practice. Moreover, it should be shown that safety require- ments are optimal and that no side effects can be expected (11). The safety evalua- tion is mandatory for cosmetics in Europe, according to articles 2, 12, and 13. In the United States, this would mean that a subclass of drugs (cosmeceuti- cals) are registered in a similar manner as over-the-counter products (12). It would be beneficial if these countries could agree on the definitions of cosmetics and drugs and, in so doing, define cosmeceuticals as a subclass of cosmetics. This would prevent the current situation in which certain products are registered as drugs in the United States (sunscreens) and as cosmetics or cosmeceuticals in Europe and Japan. Evidence that cell shedding from plantar stratum corneum in vitro involves endogenous proteolysis of desmosomal protein desmogein. Aging skin was to be accepted as an inevitable, irreversible, and trivial conse- quence of getting old. These observations have coincided with several pertinent phenomena: (1) the incredible growth of scientific knowl- edge in recent years; (2) people in western populations living longer and spending increased leisure time exposed to sun in outdoor activities; and (3) the rampant cosmetic claims for products that will ‘‘turn back the clock’’ to youth overnight. One is the northern hemisphere, where life is rigid, cold scientific proof is difficult, and only the hardiest survive in the frozen tundras of pharmaceutical bureaucracy and governmental regulation. The southern hemisphere is friendly and warm and things that make you ‘‘feel’’ better are considered good, rather than inherently evil because they are not ‘‘natural’’ and may prevent us from looking our age. Advocacy of the term cosmeceutical, as an attempt to compromise and bridge the gap between cosmetic and pharmaceutical, greatly enlivened the de- bate. In fact, the debate has forced us to reevaluate what we truly believe, even made us iconoclasts, willing to listen to new ideas. It has taken place during an era of unprecedented discovery about the structure and functioning of the skin, and the discussion has begun to rise above the former shrill hysteria and is now on a higher plane of logic and scientific facts. On one hand, appearance of the facial skin makes this condition so obvious to the subject and observers, which in turn makes the use of cosmetic products so appealing. On the other hand, only a pharmaceutical product can truly and meaningfully effect change in the substantial pathology of the condition. The clear demonstration of the clinical efficacy of tretinoin, a pharmaceutically active retinoid topically ap- plied for a cosmetic condition, speaks to the utility of the term cosmeceutical. Cosmetic effect should be at least a partial result of structural or functional change, which can be reproducibly demonstrated by some reliable, accurate, and validated methodology—be it clini- cal or instrumental. Topical products presently predominate in the discussion, yet nontoxic, systemic substances such as vitamins and naturally occurring sub- stances should also be considered in the definition. Distinction between intrinsic aging of the skin and photoaging has been repeatedly emphasized, but in the context of this discussion it has little relevance; skin that is visible and cosmetically deteriorated is invariably sun exposed and usually highly sun damaged.

Catabolic dominance—The predominant breaking down of more complex substances into simpler ones in living organisms buy cheap v-gel 30gm on line herbals and supplements, often resulting in a release of energy discount v-gel 30 gm fast delivery rajasthan herbals international. Chronic fatigue syndrome —A serious and complicated disorder defined by profound fatigue that is unimproved by rest and worsens with activity. Symptoms may include weakness, muscle pain, sleep problems, and impaired memory and concentration, and may result in reduced participation in daily activities. Chronic stress response— This reaction is caused by long-term activation of the stress-response system— and the subsequent overexposure to cortisol and other stress hormones that can disrupt almost all of your body’s processes— putting you at increased risk of numerous health problems. Circadian rhythms— Physical, mental, and behavioral changes that follow a roughly twenty- four-hour cycle, responding primarily to light and darkness in an organism’s environment. They are found in most living things, including animals, plants, and many tiny microbes. Clomiphene citrate (also known as Clomid)—A fertility prescription that may increase the number of eggs released at ovulation. It plays a role in bones, the circulatory system, the immune system, the nervous system, stress responses, and the metabolism of fats, carbohydrates, and proteins. This response can serve as a reliable marker of hypothalamic-pituitary- adrenocortical activity. It is used by men for erectile dysfunction, and by healthy men and women who have low levels of certain hormones, to improve well-being and sexuality, as well as for slowing or reversing aging, improving thinking skills in older people, decreasing the symptoms of menopause, and slowing the progress of Alzheimer’s disease. Diabetes—High blood sugar, present when the body cannot move sugar into its fat, liver, and muscle cells to be stored for energy. This is because the pancreas does not make enough insulin or cells do not respond to insulin normally. Dopamine—A neurotransmitter that helps control the brain’s reward and pleasure centers. It also helps regulate movement and emotional responses, and it enables us to not only see rewards but also to take action to move toward them. Double-blind trials—A drug trial in which neither the researchers nor the patients know what they are getting. The computer gives each patient a code number and the code numbers are allocated to the treatment groups so that neither the patient nor the doctors know whether the treatment is medicine or a placebo. Eczema (Atopic dermatitis)— A long-term skin disorder that involves scaly and itchy rashes. Endogenous—Caused by factors within the body, resulting from conditions within the organism. Endometriosis—A female health disorder that occurs when cells from the lining of the womb (uterus) grow in other areas of the body. This can lead to pain, irregular bleeding, and problems getting pregnant (infertility). Epidemiologists—Scientists who investigate and describe the causes and spread of disease, and develop the means for prevention or control. They respond to disease outbreaks, determining their causes and helping to contain them. Epinephrine—A hormone with neurotransmitters made in the inner core of the adrenals that help you focus and problem-solve. It creates amounts of glucose and fatty acids that can be used by the body as fuel in times of stress or danger when increased alertness or exertion is required. It is responsible for the growth of the womb (uterus), breast development, fallopian tubes, and vagina, and plays a role in the distribution of body fat in women. It is used to treat breast tenderness, cysts, cancer, fibroids, endometriosis, endometrial cancer, hot flashes, and symptoms in women who are experiencing or have experienced menopause. Fibromyalgia—A common syndrome in which a person has long-term, body-wide pain and tenderness in the joints, muscles, tendons, and other soft tissues. Fibromyalgia has also been linked to fatigue, sleep problems, headaches, depression, and anxiety. Free T3 (Free triiodothyronine)—A free T3 (fT3) test is used to assess thyroid function.

Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration proven v-gel 30 gm herbs pregnancy. Formation of extensive canalicular net- works by rat hepatocytes cultured on collagen-sandwich configuration discount v-gel 30 gm on-line herbals solutions. Expression and regulation of cyto- chrome P450 enzymes in primary cultures of human hepatocytes. Enhance cyclosphosphamide and ifosfamide activationinprimaryhumanhepatocyte cultures: response of cytochrome P- 450 inducers and autoinduction by oxazaphosphorines. A microassay for measuring cyto- chrome P4501A1 and P4502B1 activities in intact human and rat hepatocytes cultured on 96-well plates. Human liver microsomal steroid metabolism: identification of the major microsomal steroid hormone 6 betahy- droxylase cytochrome P-450 enzyme. Description of a 96-well plate assay to measure cytochrome P4503A inhibition in human liver microsomes using a selec- tive fluorescent probe. Human hepatocyte growth factor down-regulates the expression of cytochrome P450 isozymes in human hepatocytes in primary culture. Use of the polymerase chain reaction in the quantitation of mdr-1 gene expression. Measurement of cytochrome P450 gene induction in human hepatocytes using quantitative real-time reverse transcriptase- polymerase chain reaction. Minireview precision-cut tissue slices: applications in pharmacology and toxicology. Induction of cytochrome P-450- dependent enzyme activities in cultured rat liver slices. Cytochrome P-450 1 Al/1 A2 induction, albumin secretion, and histological changes in cultured liver slices. Induction of cytochrome P450 isoenzymes in cultured precision-cut rat and human liver slices. Xenobiotic metabolism in rat, dog and human precision-cut liver slices, freshly isolated hepatocytes, and vitrified precision-cut liver slices. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Perpetrators are those drugs (or other environmental factors) that inhibit or induce the enzyme that is otherwise responsible for clearing a victim drug. Likewise, genetic polymorphisms that result in the overexpression of enzyme activity [i. From a drug interaction perspective, victim drugs are also known as objects, whereas perpetrators are also known as precipitants. Reaction phenotyping is the process of identifying the enzyme or enzymes that are largely responsible for metabolizing a drug candidate. When biotransformation is known or suspected to play a significant role in the clearance of a drug candidate (which applies to most drug candidates with a log D7. Reaction phenotyping allows an assessment of the victim potential of a drug candidate. Terfenadine, cisapride, astemizole, and cerivastatin are all victim drugs, so much so that they have all been withdrawn from the market or, in the case of cisapride, made available only with severe restrictions. The relationship between fractional metabolism by a single enzyme and the fold increase in drug exposure that results from the loss of that enzyme is shown in Figure 1, which shows that the rela- tionship is not a linear one. Fractional metabolism by an enzyme determines the magnitude of the increase in drug exposure in individuals lacking the enzyme, but it does not determine its pharmacological or toxicological consequences. These are a function of therapeutic index, which is a measure of the difference between the levels of drug associated with the desired therapeutic effect and the levels of drug associated with adverse events. For drugs with a large therapeutic index, a high degree of clearance by a polymorphically expressed enzyme is not neces- sarily an obstacle to regulatory approval. Genetic polymorphisms give rise to four basic phenotypes on the basis of the combination of allelic variants that encode a fully functional enzyme (the wild-type or *1 allele designated “þ”), a partially active enzyme (designated “*”), or an inactive enzyme (designated “À”). This traditional classification scheme has been revised recently on the basis of an activity score, which assigns to each allelic variant a functional activity value from one (for the wild-type or *1 allele) to zero (for any com- pletely nonfunctional allele), as reviewed by Zineh et al. The adverse effect of warfarin, namely excessive anticoagulation that can result in fatal hemorrhaging, is an extension of its pharmacological effect (inhibition of the synthesis of 236 Ogilvie et al.

Stress-induced secretion of glucocorticoids such as cortisol evolved to help us respond to physical threats in our external environment discount v-gel 30gm with amex herbalism. Ironically buy v-gel 30 gm otc herbals product models, the same stress response is mostly triggered in our modern lives by emotional stress and causes damage. Understanding what happens during adrenal dysregulation is helpful when you’re exploring what integrative treatments may be most appropriate and effective, as described later in The Solution section for high and low cortisol. Low sodium and potassium may occur if production of aldosterone, another hormone made in the outer shell or cortex of the adrenal gland, is low from adrenal dysregulation. Aldosterone controls the level of electrolytes in your blood and urine, mediating water retention and blood pressure. Symptoms include a fast pulse, palpitations, light- headedness, fatigue, frequent urination, thirst, and salt cravings. Symptoms of this medical disorder include widespread and protracted pain, a heightened sensitivity to pressure, joint stiffness, debilitating fatigue, and difficulty sleeping. Symptoms may include weakness, muscle pain, sleep problems, and impaired memory and concentration, and they may result in reduced participation in daily activities. When allostatic load is more than you can tolerate, you are at significant risk for burnout. She started taking licorice, which helps the adrenals produce more cortisol, and got on her proper dose of thyroid medicine. Common symptoms include fatigue, headache, disturbed sleep, pain, attention deficit disorder, feelings of apathy and meaninglessness, and detachment from work. The International Labor Organization estimates that 10 percent of the workforce in North America and Europe experiences burnout. Allostatic load is a measure of biological strain on your body from poor stress response, and imbalanced cortisol is the primary marker. Recently, fifteen biological markers of stress reactivity were consolidated into an allostatic load index and shown to predict burnout. Burnout can happen to anyone, but it’s seen frequently in teachers, caregivers, nurses, doctors, and social service staff— professions in which people care directly for others and in which women predominate. A study of female teachers showed higher cortisol levels while they were teaching and lower to normal levels when not 35 teaching. Some of my patients exit adrenal overdrive only when they go on vacation, and even then they take their cell phones and laptops. The parasympathetic nervous system never has a chance to calm their systems back to normal. Our penchant for smartphones and our endless availability, overwork, multitasking, and perhaps our addiction to excess have led to an allostatic load that’s often more than we can bear. Many mainstream doctors take the easy way and prescribe an antidepressant, yet here’s what concerns me: few women are tested for hormonal causes of their ennui (for instance, 20 percent are known to have thyroid problems associated with depression), and even fewer are informed about the increased risk of stroke, breast and ovarian cancer, low libido, preterm birth, infant convulsions, and weight gain associated with taking antidepressants. Even worse, very few of these women are told that antidepressants help only the most 36 severe cases. Given the list of adverse effects, antidepressants are worse than placebo if depression is mild to moderate. Don’t get me wrong: I’m not suggesting that we discard antidepressants any time soon. I simply believe that they’re overused, few patients get full informed consent, and the root cause—often neuroendocrine imbalance—is sometimes overlooked. We want to avoid the either/or thinking that polarizes women—that makes women feel damned if they do take an antidepressant given the risks and loss of sexual interest, and damned if they don’t. Women need more choices, preferably choices that are natural and address the root cause of their discontent. Some conventional clinicians might even be resistant to considering any other options, such as looking at your cortisol levels, despite the documentation I’ve provided in this chapter (and on my webpage specifically for practitioners: http://thehormonecurebook. I believe that with a closer look, many burned-out women would show adrenal dysregulation, given the telltale signs of insulin resistance, decreased immunity, midsection weight gain, fatigue, tension, and low mood. This is when you need to find a doctor who will work with you, in a partnership that feels aligned with your goals and belief system. It’s also important to develop tools to dance with stress and to deal with a frantic lifestyle. In Appendix D, I’ve included a checklist for how to find a practitioner who is an ally in your health goals.