Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retention of many substances takes place in the pathogenesis of uremic toxicity. There are almost 100 different molecules described and defined as uremic toxins. These substances are divided into three groups according to EUTOX group calssification. Small water soluble molecules with a molecular weight less than 500 D are included into the first group. Derivate of guanidines, purines, pyrimidines and methyloamines appeared in this group. There is also an unclassified subgroup with urea as a "classical" toxin which the real role in the uraemic syndrome is still discussed. Main symptoms caused by these molecules are digestive disturbances, neurological changes, hypertension etc. We can eliminate almost all of these toxins with standard methods used during dialysotherapy. Substances with a different molecular weight but connected with proteins determine the second group. AGE-s, phenol derivates, leptin and poliamines beside others create this group. There are many studies that have proved that these toxins cause hypertension, arteriosclerosis and shortened life time of hemodialysed patients. However, melatonin toxicity is not fully proved. Different types of renal replacement therapy are not valid to purify blood from protein-bound substances. Middle molecules are included into the third group, with a molecular weight higher than 500 D. There are cytokines, neuro-transmitters e.g. beta-endorphin, metencephalin and many others accounted into this group. One of them is the parathormon, well known and considered as "universal" toxin for several years. Middle molecules are causing very different effects. They are responsible for: anemia, arteriosclerosis, chronic inflammation and generally increase dialysed patient mortality. Toxic action of several molecules described below is still not proved; however there are some ongoing studies aimed to find pathophysiological links between old and new described uremic toxins.
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PMID:[Clinical and metabolic consequences of uremic toxicity]. 1708 Jul 44

In the first stage of labor, pain is caused by distension of the cervix and low uterine segments in combination with isometric contraction of the uterus. Pain in the second stage of labor is dominated by tissue damage in the pelvis and perineum. Labor pain is due to an activation of nociceptors partly resulting from ischemia. The impulses thus generated are conducted into the spinal cord by afferent C fibers from the cervix and lower uterine segments, and by afferent Adelta and C fibers from the pelvis, pelvic organs and perineum. Labor pain is referred to the dermatomes T(11) and T(12) in the early stage of labor. It spreads to the neighboring dermatomes T(10) and L(1) and eventually involves the dermatomes S(2-4) during the second stage of labor and delivery. As in any other type of pain, labor pain stimulates respiration. This reduces the CO(2) concentration in the blood so that, in pain-free periods, respiratory stimulation is lacking and, in consequence, oxygen concentration in maternal and fetal blood is lowered. Pain-induced sympathetic activation will increase cardiac output in a way that may be deleterious in parturients with heart disease, eclampsia and anemia. Moreover, slowing of gastric emptying may cause nausea and vomiting, and slowing of intestinal propulsive movements may result in ileus and oliguria. An increase in plasma catecholamines and glucocorticoids influences uterine contractions. The amount of beta-endorphin released from the pituitary and placenta into the blood is relatively high but obviously not sufficient to depress pain effectively. Adequate nerve block and epidural anesthesia, as well as measures to relieve anxiety, will help markedly to reduce the risks associated with labor pain.
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PMID:[Labor pain-causes, pathways and issues.]. 1841 27

Non-clinical studies were conducted to evaluate the toxicity of Antalarmin, a corticotropin-releasing hormone type 1 receptor antagonist being developed for therapy of stress-related pathologies. Antalarmin was not genotoxic in bacterial mutagenesis assays, mammalian cell mutagenesis assays, or in vivo DNA damage assays. In a 14-day range-finding study in rats, Antalarmin doses >or=500 mg/kg/day (3,000 mg/m(2)/day) induced mortality. In a 90-day toxicity study in rats, no gross toxicity was seen at doses of 30, 100, or 300 mg/kg/day (180, 600, or 1,800 mg/m(2)/day, respectively). Antalarmin (300 mg/kg/day) induced mild anemia, increases in serum gamma-glutamyl transferase activity, and microscopic hepatic pathology (bile duct hyperplasia and epithelial necrosis, periportal inflammation). Microscopic renal changes (cortical necrosis, inflammation, hypertrophy, nephropathy) were observed in rats at all Antalarmin doses. In a 14-day range-finding study in dogs, Antalarmin doses >or=50mg/kg/day (1,000 mg/m(2)/day) induced repeated emesis and bone marrow suppression. In a 90-day toxicity study in dogs, Antalarmin (4, 8, or 16 mg/kg/day (80, 160, or 320 mg/m(2)/day, respectively)) induced bone marrow and lymphoid depletion, but no gross toxicity. Comparative in vitro studies using rat, dog, and human neutrophil progenitors demonstrated that canine bone marrow cells are highly sensitive to Antalarmin cytotoxicity, while rat and human bone marrow cells are relatively insensitive. As such, the bone marrow toxicity observed in dogs is considered likely to over-predict Antalarmin toxicity in humans. The hepatic and renal toxicities seen in rats exposed to Antalarmin identify those tissues as the most likely targets for Antalarmin toxicity in humans.
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PMID:Integration of in vivo and in vitro approaches to characterize the toxicity of Antalarmin, a corticotropin-releasing hormone receptor antagonist. 1842 34

Addison's disease is a rare disorder in patients with end-stage renal disease (ESRD). In patients, the diagnosis of Addison's disease is difficult in clinical practice because most of the clinical findings of this disease are similar to those of the renal failure. We present a 51-year-old male patient, who underwent hemodialysis therapy for 8 years, diagnosed with Addison's disease after having myalgia, skin hyperpigmentation, weight loss, sweating, and nausea for the past few weeks. The physical examination was completely normal except for muscle weakness, hyperpigmentation on labial mucosa and skin in a patient. The laboratory tests revealed anemia and hypoglycemia. Serum cortisol, adrenocorticotropic hormone (ACTH) levels, and ACTH stimulation test results were consistent with Addison's disease. Adrenal computerized tomography revealed bilateral atrophic glands. Additionally, it was found that elevated serum thyroid stimulating hormone levels and antithyroid peroxidase antibody titer were positive. Our purpose is to emphasize that physicians should be alert to the potential for additional different conditions particularly in terms of adrenal failure in patients with ESRD.
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PMID:Misdiagnosis of Addison's disease in a patient with end-stage renal disease. 2121 12

Hypoadrenocorticism (Addison disease) is an uncommon condition in dogs and even more rare in cats. Hypoadrenocorticism is most often caused by immune-mediated destruction of the adrenal glands resulting in decreased mineralocorticoid and glucocorticoid production. Although less common, some dogs with hypoadrenocorticism have normal serum electrolytes. Hypoadrenocorticism causes a wide variety of clinical symptoms including gastrointestinal upset, weakness, weight loss, and hypovolemia. Laboratory and diagnostic findings vary, but classic abnormalities include hyperkalemia, hyponatremia, azotemia, anemia, and lack of a stress leukogram. However, many other diseases present with similar symptoms and diagnostic findings. Definitive diagnosis requires adrenocorticotropic hormone (ACTH) stimulation testing to demonstrate low basal and post-ACTH cortisol levels. In some cases, ACTH level or basal- and ACTH-stimulated aldosterone levels must also be measured. The prognosis for hypoadrenocorticism is good with appropriate mineralocorticoid and glucocorticoid supplementation.
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PMID:Canine hypoadrenocorticism: pathogenesis, diagnosis, and treatment. 2581 48

A 62-year-old man, receiving chronic haemodialysis and suffering from alcoholic liver cirrhosis and chronic pancreatitis, presented with hypoglycaemic coma. Plasma cortisol was undetectable (< 5.5 nmol/L) with suppressed adrenocorticotropic hormone (ACTH), which established a diagnosis of adrenal failure due to ACTH deficiency. Twenty-five milligrams of oral hydrocortisone eradicated hypoglycaemia. Presentation of adrenal failure in this patient was atypical because he was hypertensive, serum electrolytes including sodium were normal and anaemia was unremarkable, which were all due to end-stage renal disease and its treatment with haemodialysis. As far as we are aware, this is the first case report of hypoglycaemic coma due to adrenal failure in a chronic haemodialysis patient.
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PMID:Hypoglycaemic coma due to adrenal failure in a chronic haemodialysis patient. 2598 98

An 11-year-old neutered male Alaskan Malamute mixed-breed dog was presented with a complaint of polyuria/polydipsia (PU/PD), weight loss, tachypnea, regurgitation, and a previous history of nontreated osteosarcoma of the right distal radius, diagnosed 21 months prior. On physical examination, an abdominal mass was palpated. The abdominal mass was aspirated and cytologically diagnosed as a neuroendocrine tumor, suspected to be a pheochromocytoma. Laboratory examination revealed a mild anemia and thrombocytopenia, markedly elevated ATP and ALP activities, and moderate hypercalcemia. A low-dose dexamethasone suppression test and endogenous adrenocorticotropic hormone (ACTH) concentration were compatible with pituitary hyperadrenocorticism. On urinalysis, proteinuria was noted as well as a high urine metanephrine/creatinine ratio, consistent with a diagnosis of pheochromocytoma. The dog was treated with supportive care and euthanized 6 months later due to decreasing quality of life. On necropsy, an extra-adrenal pheochromocytoma (paraganglioma) was diagnosed in the caudal abdomen, and a pituitary adenoma and an osteosarcoma of the right distal radius were confirmed.
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PMID:Paraganglioma, pituitary adenoma, and osteosarcoma in a dog. 2742 77

Erythropoietin (EPO), known primarily for its erythropoietic activity, is commonly used clinically to treat anemia of chronic kidney disease. However, the expression of EPO receptor (EpoR) beyond erythroid tissue provides for potential extrahematopoietic effects of EPO, including EPO regulation of metabolic homeostasis (Zhang et al., 2014). Small clinical studies have shown that EPO treatment in patients with end-stage renal disease improved glycemic control and insulin sensitivity. Studies in animal models have shown that EPO regulation of metabolism is mainly attributed to its response in fat, and the hypothalamus-pituitary axis (Dey et al., 2016; Dey, Scullen, & Noguchi, 2015; Teng, Gavrilova, et al., 2011; Wang et al., 2013) and is not dependent on its hematopoietic activity. EpoR expression in the hypothalamus is localized to the neurons expressing proopiomelanocortin (POMC) in the arcuate nucleus region, the most important site in the brain for the regulation of physiological energy expenditure. EPO treatment increases POMC production in anorexigenic POMC neurons in the hypothalamus. In the pituitary, EPO modulates the secretion of the POMC-derived peptide, adrenocorticotropic hormone (ACTH) that regulates physiological and metabolic stress response. With EPO produced by cells in the brain, such as astrocytes, and with EPO-stimulated POMC expression in the hypothalamus and EPO-inhibited ACTH secretion in the pituitary, EPO signaling contributes to the hypothalamic-pituitary axis as a major regulator of glucose metabolism and energy homeostasis.
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PMID:Erythropoietin and Hypothalamic-Pituitary Axis. 2862 13


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