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Development of a simple screening system for endocrine disruptors.

BACKGROUND: An endocrine disruptor is a synthetic chemical, which causes adverse effects in an organism, or its progeny, after causing perturbations in the endocrine system. It is important to know which synthetic chemicals have endocrine-disrupting action. However, an increasing number of synthetic chemicals are being produced by modern synthetic chemistry, and the examination of endocrine disruptor potential has not yet caught up with the advances in synthetic chemistry. In this study, we have developed such a screening system for detecting synthetic chemicals with estrogen-like effects. MATERIAL/METHODS: The system was based on the yeast one-hybrid system. Both HIS3 and lacZ reporter genes connected to three tandem copies of the estrogen response element were prepared. Gal4-estrogen receptor is a fusion protein made from the activation domain (AD) of the yeast GAL4 transactivator gene and then incorporated into a plasmid, which was transfected into the YM4271 yeast cell strain. The estrogen effect was judged by this developed screening system. RESULTS: A dual reporter assay-system was established by transfection of the both HIS3 and lacZ reporter genes into the yeast cells. This screening system enabled the detection of as little as 10-12 mol of beta-estradiol. CONCLUSIONS: These results show that this newly developed dual assay is useful for the screening of endocrine-disruptors that have estrogen-like action.

Dose-Response Relationship, Drug↗

[Research of ultra-structural pathological changes of nervous, endocrine and immune system in heroin addicts].

OBJECTIVE: To investigate ultrastructural pathological changes of Heroin-Addicts. METHODS: Heroin-Addicts' central nervous system, endocrine system, immune system and reproductive system in 4 cases are observed by using transmission electron microscope(TEM). RESULTS: The changes of central nervous system are mitochondrion swelling, crista fragmentation and disappear. Endoplasmic reticulum dilation, nervous fibres and cell organelles reduction; mitochondrion swelling, Partial crista fragmentation and endoplasmic reticulum dilation are also found in endocrine system; Lymphocytes reduction, cytoplasm ingredient reduction and dead lymphocytes increase in immune system; in reproductive system, spermatogenic cells and cell organelles are reduced in the male and follicle disappeared in the female. CONCLUSION: Ultra-structural pathological changes of heroin-addicts are presented acute, chronic oxygen deficiency degeneration and necrosis.

Central Nervous System↗

[Prevalence of CD56 /NCAM molecule in nervous system immune system and endocrine glands--accidental coincidence?].

The authors presented advances in the research on isoform of neural cell adhesion molecule CD56/NCAM, which appears to raise interest not only in biology, but also in clinical medicine. Molecular aspects of its synthesis have been presented and universal features of this protein have been underlined. It appears to play an important role in body homeostasis and especially in the interactions between neural, immune and endocrine systems. In relation to the immune system there are data suggesting significance of local protective and regulatory mechanisms in the liver linked to so called NKT (CD56+) cells. Main sites of prevalence of CD56/NCAM have been indicated both in physiology and pathology, especially in malignancy. CD56/NCAM incidence is common in tumors of neuroectodermal and endocrine origin. Besides it may be expressed on cells of several hemopoetic neoplasms originated both, from lymphoid and myeloid lineage. Moreover, the attention was paid to CD56/ NCAM expression in atypical sites as for example on epithelia of bile ducts in children with extrahepatic biliary atresia and on cells of pancreatic ducts in the course of chronic pancreatitis.

Adrenal Glands↗

Metabolic and membrane-altering toxins, molecular differentiation factors, and pheromones in the evolution and operation of endocrine-signalling systems.

The endocrine systems of vertebrates and higher invertebrates may have evolved functionally from as far back on the evolutionary scale as bacteria and early multicellular organisms and their biological communities, which have been shown to produce a variety of cyclic nucleotides, peptides, fatty acids, prostaglandins and sterols with endocrine-altering effects in primative as well as more highly evolved species.

Animals↗

The avian egg as a test system for endocrine disrupters: effects of diethylstilbestrol and ethynylestradiol on sex organ development.

Many environmental contaminants are known or suspected to interfere with hormonal function in animals. In vivo test methods to detect and characterize chemicals that disrupt the endocrine system are therefore urgently needed. In this study, we assessed the usefulness of abnormalities of the reproductive organs as test endpoints for estrogenic activity of xenobiotics in Japanese quail embryos. Two synthetic estrogens, diethylstilbestrol (DES) and ethynylestradiol (EE2), were injected into the yolks of embryonated eggs. At a dose as low as 2 ng EE2/g egg, all male embryos became feminized, containing ovary-like tissue in the left testis. The extent of feminization of the testes was determined by measuring the relative area of the ovary-like component. Persistent Müllerian ducts (oviducts) in male embryos, and malformations of the Müllerian ducts in females occurred at 2 ng EE2/g egg and higher doses. DES was approximately one-third to one-tenth as potent as EE2. The morphological changes studied were dose-dependent, indicating that they are useful as test endpoints for estrogenic activity. Feminization of the left testis in males proved to be the most sensitive endpoint. We propose the quail egg as a simple in vivo test system for estrogenic compounds.

Androgen-Insensitivity Syndrome↗

Minireview: overview of the renin-angiotensin system--an endocrine and paracrine system.

Since the discovery of renin as a pressor substance in 1898, the renin-angiotensin (RAS) system has been extensively studied because it remains a prime candidate as a causative factor in the development and maintenance of hypertension. Indeed, some of the properties of the physiologically active component of the RAS, angiotensin II, include vasoconstriction, regulation of renal sodium and water absorption, and increasing thirst. Initially, its affect on blood pressure was thought to be mediated primarily through the classical endocrine pathway; that is, the generation of blood-borne angiotensin with actions in target tissues. More recently, however, it has become appreciated that a local autocrine or paracrine RAS may exist in a number of tissues, and that these may also play a significant role in regulating blood pressure. Some of the difficulties in studying tissue RAS stem from the limitations of pharmacology in not differentiating between RAS products made systemically from those synthesized locally. However, the development of transgenic animals with highly specific promoters to target the RAS to specific tissues provided important tools to dissect these systems. Thus, this minireview will discuss recent advances in understanding the relationship between endocrine and paracrine (tissue) RAS using transgenic models.

Animals↗

Endocrine disorders affecting the cardiovascular system.

Endocrine disorders can affect the cardiovascular system in many ways. Patients admitted to an intensive care unit with primary cardiovascular diagnoses may have underlying endocrine dysfunction that can cause or adversely influence cardiovascular problems. Early diagnosis and treatment of endocrine disease can often prevent or reverse cardiovascular problems and contribute to more acceptable patient outcomes.

Cardiovascular Diseases↗

Aluminum: impacts and disease.

Aluminum is the most widely distributed metal in the environment and is extensively used in modern daily life. Aluminum enters into the body from the environment and from diet and medication. However, there is no known physiological role for aluminum within the body and hence this metal may produce adverse physiological effects. The impact of aluminum on neural tissues is well reported but studies on extraneural tissues are not well summarized. In this review, the impacts of aluminum on humans and its impact on major physiological systems are summarized and discussed. The neuropathologies associated with high brain aluminum levels, including structural, biochemical, and neurobehavioral changes, have been summarized. In addition, the impact of aluminum on the musculoskeletal system, respiratory system, cardiovascular system, hepatobiliary system, endocrine system, urinary system, and reproductive system are discussed.

Aluminum↗

Local cardiac renin-angiotensin system: hypertension and cardiac failure.

In addition to the effect on arterial pressure, angiotensin II, the effector peptide of the renin-angiotensin system (RAS), exerts mitogenic and growth promoting effects on cardiac myocytes and non-myocytic elements; and both of these effects significantly contribute to the development and progression of hypertensive heart disease (HHD). The traditional concept of the RAS as a systemic, endocrine system has been expanded and the identification of its components in many organs and tissue has been amassed. This paper reviews evidence that supports the concept that the cardiac RAS participate importantly in the development and risk of HHD.

Aldosterone↗

Reduced growth of calves and its reversal by use of anabolic agents.

Disease has profound effects on the immune system, endocrine system, and on the growth process. Since diseases are catabolic to the animal, there is current interest in the possible role of anabolic hormones to counter the effects of disease in general and minimize the effects of a disease process on growth and development. A number of anabolic hormones, such as growth hormone (GH) and estradiol + progesterone (EP), have been studied for their role in enhancing growth and stimulating immune function and are thus candidates for hormonal intervention in disease processes. GH has been shown to be effective in countering some of the deleterious effects of endotoxemia but was ineffective in a parasitic disease model. Studies with EP have shown similar success with both endotoxemia and a parasitic disease model. Moreover, GH and EP do not share a common mechanism of action, suggesting that the effects are not simply due to anabolic actions. While the mechanism of action of GH in endotoxemia has been examined, the effects of EP are via an unknown mechanism, possibly by inhibition of IL-I action or inhibition of nitric oxide overproduction.

Animals↗

Surgical management of palmar hyperhidrosis.

Hyperhidrosis is an idiopathic pathologic condition characterized by excessive sweating beyond that required to cool the body. Disturbance of the central nervous system, endocrine system, or obesity has been associated with this condition. Patients have a history of several years of occupational or social embarrassment. Individuals of Japanese ancestry and Jews of Northern African, Yemeni, or Balkan descent are predisposed to the condition. Nonoperative therapy is merely temporizing and unacceptable because of lack of efficacy or side effects. Surgical intervention provides effective and permanent control. The key to surgical correction appears to be the division of the sympathetic chain above the T-2 ganglion and below the T-3 ganglion of the involved side with removal of the entire T2-3 segment with its corresponding spinal nerves. This paper presents our experience with the dorsal thoracic approach for interruption of sympathetic innervation for severe palmar hyperhidrosis. We also review surgical efficacy of various approaches to the sympathetic chain, as well as possible side effects of operative intervention.

Adult↗

The future: critical knowledge about anti-itch therapy.

Itch is an extremely frequent and enervating symptom of many diseases. Current anti-itch therapy, which is based almost exclusively on an "immunocentric" viewpoint, is often unsatisfactory. Recent studies show that this symptom is in fact the result of a complex interplay among skin, nervous system, endocrine system, and immune system. This explains the frequent failure of therapeutic strategies focused only on a single factor and suggests the usefulness of a polypharmacologic symptomatic treatment, designed on a case-by-case basis as a result of a multidisciplinary approach. We discuss the perspectives of anti-itch therapy in light of the new pathogenetic and pharmacologic acquisitions.

Antipruritics↗

Identifying critical windows of exposure for children's health.

Several authors have considered the importance of exposure timing and how this affects the outcomes observed, but no one has systematically compiled preconceptional, prenatal, and postnatal developmental exposures and subsequent outcomes. Efforts were undertaken to examine the information available and to evaluate implications for risk assessment for several areas: a) respiratory and immune systems, b) reproductive system, c) nervous system, d) cardiovascular system, endocrine system, and general growth, and e) cancer. Major conclusions from a workshop on "Critical Windows of Exposure for Children's Health" included a) broad windows of sensitivity can be identified for many systems but detailed information is limited; b) cross-species comparisons of dose to target tissue and better data on the exposure-dose-outcome continuum are needed; c) increased interaction among scientific disciplines can further understanding by using laboratory animal results in designing epidemiological studies and human data to suggest specific laboratory studies on mechanisms and agent-target interactions; and d) thus far, only limited attention has been given to peripubertal/adolescent exposures, adult consequences of developmental exposures, and genome-environment interactions. More specific information on developmental windows will improve risk assessment by identifying the most sensitive window(s) for evaluation of dose-response relationships and exposure, evaluation of biological plausibility of research findings in humans, and comparison of data across species. In public health and risk management, information on critical windows may help identify especially susceptible subgroups for specific interventions.

Adolescent↗

Evaluation of the ergogenic properties of ginseng: an update.

Ginseng has been used in the Orient for several thousand years as an 'adaptogenic' as well as a 'restorative' agent. It has been used to treat nervous disorders, anaemia, wakefulness, dyspnoea, forgetfulness and confusion, prolonged thirst, decreased libido, chronic fatigue, angina and nausea. Although the mechanisms underlying the alleged effects of ginseng remain to be elucidated, there is an extensive animal literature dealing with the effects of ginseng on the cardiovascular system, central nervous system, endocrine system, metabolism, and immune system. In our previous review dealing with the efficacy of ginseng, we concluded that while studies with animals show that ginseng, or its active components, may prolong survival to physical or chemical stress, there is generally a lack of controlled research demonstrating the ability of ginseng to improve or prolong performance in fatigued humans. In this review, we extend our earlier analysis on the potential efficacy of ginseng use in the enhancement of physical performance and modification of fatigue states. Our analysis reveals that published literature appearing since our earlier review has not resolved the equivocal nature of research evidence involving animals or humans. Also, the lack of unanimity in this research can be explained on the basis of various methodological problems such as inadequate sample size and lack of double-blind, control and placebo paradigms. In addition, the absence of acceptable approaches to the problem of 'sourcing', in concert with an absence of compliance data in human research, further complicates the interpretation of this research literature. Nevertheless, the use of ginseng continues to grow, and current sales are estimated to be over $US300 million annually. There is clearly a need for systematic research dealing with the efficacy of ginseng, and this research needs to take into account basic, fundamental design considerations if there is to be any hope of establishing whether or not ginseng possesses efficacy.

Affect↗