By L. Farmon. Creighton University. 2019.
Proximal dysphagia is caused by involvement of striated mus- cle in the pharynx or proximal esophagus discount kamagra effervescent 100 mg with mastercard. This involvement correlates well with the sever- ity of the muscle disease and is steroid-responsive 100 mg kamagra effervescent with amex. Distal dysphagia purchase kamagra effervescent 100mg on-line, which ofen presents as refux discount 100mg kamagra effervescent otc, is related to involvement of nonstriated muscle and appears to be more frequent in patients who have an overlap syndrome with scleroderma or another collagen vascular disorder. Dysphagia is associated with a poor prognosis and correlates with the presence of pulmonary involvement. Pulmonary disease occurs in dermatomyositis and polymyositis in approximately 15% to 30% of patients (Marie et al. Lung disease may also occur as a direct complication of the muscle disease, such as hypoventila- tion or aspiration in patients with dysphagia, or may be a result of treatment, such as with opportunistic infections or drug-induced hypersensitivity pneumonitis. In a retrospective review of 70 patients with myositis-associated interstitial lung dis- ease seen at Mayo Clinic between 1990 and 1998, most of the patients presented with either symptoms of lung disease or symptoms of myositis alone, whereas only 15 patients pre- sented with the involvement of both simultaneously (Douglas et al. In general, the lung disease was at frst felt to be a pneumonitis that was antibiotic resistant. Biopsy of the lung revealed non-specifc interstitial pneumonitis or difuse alveolar damage in a major- ity of those who were biopsied. It is unclear exactly how many of these patients had dermatomyosi- tis, but perhaps between 8 and 12. Patients with Jo-1 antibodies (19 of 50 who were tested) had roughly the same fea- tures and prognosis as those who did not have this antibody. Var- ious abnormalities have been described which most commonly include conduction defects and rhythm disturbances. Although congestive heart failure, pericarditis, and valvular dis- ease may occur, they are much less frequent. Depending on the report, cardiac manifes- tations may occur in up to 50% of patients, but only a small proportion of these patients manifest symptoms. It is not known whether the identifcation of asymptomatic abnor- 250 Ruth Ann Vleugels and Jeffrey P. Calcinosis cutis is manifested by frm, yellow-white or skin-col- ored nodules, which ofen occur over bony prominences. Occasionally, these nodules can extrude through the surface of the skin, in which case secondary infection may occur. Cal- cifcation of the muscles is ofen asymptomatic and may be seen only on radiological ex- amination. In severe forms, the calcinosis can cause loss of function, and rarely, bone for- mation is possible. This is a change from the previous notion that all patients with dermatomyositis would have some degree of muscle involvement by defnition if physi- cians simply investigated sufciently to fnd it. Within current nomenclature proposed by Sontheimer, clinically amyopathic dermatomyositis includes patients with both amyo- pathic and hypomyopathic dermatomyositis (Sontheimer, 2002). Amyopathic dermatomyositis, historically known as dermatomyositis sin myositis (Bohan et al. By defnition, these patients must not have received two consecu- tive months or more of systemic immunosuppressive therapy in the frst six months afer skin disease onset and must not have received medications known to cause dermatomyosi- tis-like skin changes (Sontheimer, 2002). Tese cases can be referred to as provisional amy- opathic dermatomyositis until two years afer diagnosis, at which point they can be called confrmed amyopathic dermatomyositis. Using these criteria, 1020% of patients with der- matomyositis seen in academic health centers have clinically amyopathic disease (Jorizzo, 2002). Although amyopathic dermatomyositis presents with cutaneous disease indistinguish- able from that of classic dermatomyositis, it is considered a distinct entity rather than a group of patients in which muscle abnormalities are not yet detectable. Importantly, these fndings do not reliably predict the onset of clinically signifcant muscle disease at a later time and should therefore not necessarily warrant more aggressive therapeutic intervention. Sontheimer reported that none of the patients with hypomyopathic dermatomyositis in the series mentioned above had devel- oped clinically signifcant muscle weakness at the time of follow-up despite an average du- ration of skin disease of 5. Similar to classic dermatomyositis, there is a female predominence, a peak onset in adults in the ffh and sixth decades, and a pediatric population afected by amyopathic dermatomyositis. Finally, similar to classic dermatomyositis, amyopathic deramtomyositis has associations with both pulmonary disease and cancer, mandating that these patients be followed for manifestations of both interstitial lung disease and malignancy. Overall, the reported frequency of malignancy in dermat- omyositis has varied from 6% to 60%, with most large population-based cohort studies re- vealing a frequency of about 20 to 25%. While polymyositis patients had a slight increase in cancer frequency, it was not highly signifcant and could be explained by a more aggressive cancer search creating a diagnostic suspicion bias. In this study, patients with malignancy-associated dermatomyositis were more frequently male and over the age of forty-fve and were less likely to have inter- stitial lung disease. In the recent population-based study from Mayo Clinic, malignancy was present in 28% of patients (Bendewald et al. In addition, the myositis may follow the course of the malignancy (a paraneoplastic course) or may follow its own course independent of the treatment of the malignancy. Studies demonstrating the benefts of cancer surgery on myositis as well as those showing no relationship of the myositis to the malignancy have been reported. In some Southeast Asian populations, nasopharyngeal can- cer seems to be overrepresented (Peng et al. Of note, the increased risk of malignancy occurs with adult dermatomyositis, but not with the juvenile form of the disease. In the past, there was concern about whether the use of immunosuppressive therapies would predispose the patient to an excess cancer risk. This has not proven to be the case in several studies, with most cancers being reported within the frst three years following diagnosis. A fulminant course may be present, but most ofen the onset is indolent and chil- dren are frst thought to have viral infections or dermatitis. A recent report detailed the chronic nature of this disease in children, with many patients requir- ing therapy to suppress their disease activity more than three years afer diagnosis (Huber et al. In one study it was noted that the development of calcinosis was not related to initial therapy, but was associated with a lower score on an assessment instrument of physical function. Additional studies demonstrate that early and aggressive intervention with sys- temic therapy seems to decrease the risk of development of calcinosis (Fisler et al. This has been best doc- 6 Dermatomyositis 253 umented for hydroxyurea in which de-challenges and re-challenges have been performed (Daoud et al. None of the cases associated with hy- droxyurea had associated mysotis, however, greater than seventy-fve percent of the non- hydroxyurea cases reported myositis and several had associated pulmonary involvement. Once the presence of cutaneous disease has been established, a systematic investigation for the presence of muscle disease, systemic disease, and / or a potentially associated malignancy should ensue. Serologic tests are ofen ordered, but their clinical application is at best controversial. Perhaps as fur- ther studies are performed, serologic testing will become clinically useful. Evalu- ation has several purposes: assessment of severity, prediction of prognosis, and identifca- tion of associated disorders. The severity of the myositis ofen correlates with enzyme levels and degree of weakness. The likelihood of malignancy increases with age and the sites vary depending on the patients age. Malignancy evaluation is repeated annually for at least the frst three-years following di- agnosis as well as with any new symptoms. The overrepresentation of cancer in these pa- tients seemingly approaches normal levels afer three-years (Hill et al. Bedrest is ofen valu- able in the individual with progressive weakness; however, this must be combined with a range-of-motion exercise program to prevent contractures. Patients who have evidence of dysphagia should have the head of their bed elevated and should avoid eating meals imme- diately before retiring. Studies demon- strate that patients with infammatory muscle disease who participate in these programs have improved muscle strength and endurance and note reduced disease activity. In addi- tion, improvement in strength has been demonstrated even in the course of active disease, rather than inducing fares in muscle involvement (de Salles Painelli et al.
Current practices in performing frozen sections for thyroid and parathyroid surgery cheap 100 mg kamagra effervescent visa. Prospective study comparing scrape cytology and frozen section in the intraoperative identification of parathyroid tissue purchase 100 mg kamagra effervescent amex. Role of gamma probes in performing minimally invasive parathyroidectomy in patients with primary hyperparathyroidism: optimization of preoperative and intraoperative procedures order 100mg kamagra effervescent free shipping. Intraoperative localization of parathyroid glands with gamma counter probe in primary hyperparathyroidism: A prospective study generic kamagra effervescent 100 mg online. Diagnosis of parathyroid adenomas: efficacy of measuring parathormone levels in needle aspirates of cervical masses. Direct, minimally invasive adenomectomy for primary hyperparathyroidism: An alternative to conventional neck exploration? Profile of a clinical practice: Thresholds for surgery and surgical outcomes for patients with primary hyperparathyroidism: A National survey of endocrine surgeons. Surgeon volume as a predictor of outcomes in inpatient and outpatient endocrine surgery. Do the National Institutes of Health consensus guidelines for parathyroidectomy predict symptom severity and 220 Thyroid and Parathyroid Diseases New Insights into Some Old and Some New Issues surgical outcome in patients with primary hyperparathyroidism? A quick intraoperative parathyroid hormone assay in the surgical management of patients with primary hyperparathyroidism: a study of 206 consecutive cases. Intraoperative confirmation of parathyroid tissue during Parathyroid Exploration: A Retrospective Evaluation of the Frozen Section. A spike in parathyroid hormone during neck exploration may cause a false-negative intraoperative assay result. Additionally, other members are called orphans and could either bind to ligands that have not yet been identified or modulate gene expression in a ligand independent fashion (Webb et al. This family of proteins can be modulated by natural and synthetic ligands and are therefore promising targets for drug discovery. The natural ligands may include different kinds of plant molecules or even a combination of compounds present in raw extracts of medicinal plants. This extension in the ligand structure blocks normal receptor function by occupying the pocket region where the hormone normally binds. Although no direct interaction of the compound with estrogen receptor seems to be necessary for estrogenic action, the author classified this plant ligand as a novel class of potent phytoestrogen (Chan et al. Also sesame ligands, from Sesamum indicum (flowering plant, native to Africa and widely naturalized in tropical regions around the world), and their metabolites have been evaluated for estrogenic activities (Pianjing et al. According to the author, this phytochemical could be developed as a therapeutic agent to treat both androgen-stimulated and castration-resistant prostate cancer. This species, also known as Chinese liquorice, is a flowering plant native to Asia, which is used in traditional Chinese medicine. From these studies, we can conclude that diet has a significant influence on the activity of the androgen receptors and possibly other types of nuclear receptor. If so, a wide range of diseases may be avoided by increasing intake of food that contains hormone analogs or other nuclear receptor modulators. In a work about patients where thyroid have been removed partially or totally due to thyroid cancer, the plant R. This interferes with thyroid hormone transport proteins and 5-deiodinase type I activities in peripheral tissues, leading to altered thyroid hormone action at the cellular level. Synthetic flavonoids, such as F21388, which is structurally similar to thyroxine, cross the placenta and also reach the fetal brain of animal models (Hamann et al. The cruciferous family was also referred when we consider thyroid modulators in plant. In a study that examined the effects of both soy-foods and specific phytoestrogenic molecules on the development of thyroid cancer in humans it was demonstrated that intake of plants from that family decreases the risk of this kind of cancer (Horn-Ross et al. The Synthetic and Plant Derived Thyroid Hormone Analogs 227 compounds that may be associated with this effect are, according to the author, isoflavones, lignans and 2-hydroxyestrogens. Although anti-carcinogenic response was linked to those molecules, it was not explained how they may affect metabolism in humans or their physiological mechanism of action. It seems to have a cross talk between the thyroid hormone receptor and the estrogen receptor. Our recent results (Cunha Lima et al, not published) have shown that ligands originally referred for thyroid diseases have activated estrogen receptor in transient transfection assays. This could explain why phytoestrogens have caused responses in thyroid cancer and thyroid hormone analogs have also effect in breast cancer, for example. The most severe responses are those related to the heart, which can lead to serious cardiopathies and are due to the isoform of the receptor, as cited previously. A single base difference in the pocket of the protein can lead to these harmful responses. This means that we have a two step work on the search for new agonists and antagonists: they should mimesis the response caused by the thyroid hormone (or antagonize it, depending on the disease) and second, they should have a specificity to avoid tachycardia and more serious heart problems. Since women hormone analogs may interfere with the function of the thyroid, as referred before with some flavonoids, they may have beneficial effects in cases of thyroid cancer. Nevertheless those compounds may influence thyroid actions at the cellular level and could cause side effects harmful for healthy individuals. This approach has an increased probability of success in locations with higher biodiversity; because they contain a privileged number of candidate species. Along with botanical diversity, ethnobotanical surveys are likely to succeed where the population has an in depth knowledge of medicinal plants and systematically uses those plants to treat a range of metabolic disorders. The city has hot, tropical weather, with average daily highs reaching 170C in the winter and 380C in the summer. Northeastern Brazil is the economically poorest region of the country, 60% of the active population has an income under $100 per month, (Brazilian Institute of Statistics and Geography, 2003) and many residents depend on medicinal plants to treat multiple ailments and diseases. Leaves were most commonly used in preparations (87%), followed by the whole plant (10%), and fruits and seeds (3%). The majority of the preparation (88%) required decoction (boiling the plant tea for at least 5 minutes); the rest includes infusion (liquid preparation without boiling) and ingestion of the fresh plant. Among the plant parts used the leaves were more frequent (87%), followed by the whole plant (10%), seeds and fruits (3%). The families Asteraceae (17%), Lamiaceae (15%) and Myrtaceae (12%) were the most cited among plants referred. This survey identified botanical families frequently cited in other surveys of medicinal plant use in Brazil. In two studies conducted in the state of Rio de Janeiro, one in Rio city (Azevedo & Silva) and one in the reservation of Mangaratiba (Medeiros et al. These data suggest that the Asteraceae and Lamiaceae family have excellent pharmacological potential on different kinds of diseases and they are currently being investigate in many clinical studies. Among the plants used for obesity control, with probable effect on the metabolism, Borreria verticillata (carqueija or vassorinha-de-boto) was the species with the highest number of references in our survey. This plant, also used for the treatment of diabetes type 2, is found across Brazil. Phytochemical studies have demonstrated the presence of alcaloids and iridoids (Vieira et al. The teas of Tragia volubilis leaves and the seeds of Ocimum gratissimum were also used in combination with niphedipine and aspirin. The most extreme side effects symptoms are associated with the T4 hormone replacement for patients whose thyroid was partially or completely removed. In addition to the plants cited for treatment of thyroid problems, watercress (Nasturtium officinale R. Although the majority of the patients did not tell their doctors they were using those teas, there are no reported adverse side effects due to the combination of the plant products and the medications indicated, nor any reference in the literature about harmful effect of such interaction. Ethnobotanical surveys are good source of information for drug candidates and offer a less expensive way of finding hormone analogs than the design of synthetic compounds. The cited information represents an important source of regional knowledge on plants with pharmacological potential and presents 31 candidates (Table 1) that might contain triiodothyronine (T3) and thyroxin (T4) analogs, including agonists, antagonists and other compounds able to modulate thyroid receptor that may act against metabolic disorders. In particular, the capital of Bahia has numerous plants used by inhabitants to treat diseases and this use is part of the local culture, based in the Candombl (religion of African origin which uses many plants in rituals and treatments). Therefore, it is necessary to scientifically systematize and analyze this phytotherapic knowledge so that those species can be identified and their pharmacological properties tested. Table 2 lists the species referred in this survey that had their active principles identified and/or properties confirmed, and the bibliographic references where the data was obtained. These works include results from clinical and experimental studies aiming the confirmation of therapeutic properties. Medicinal plants candidates for thyroid hormone analogs according to ethnobotanical research in Salvador-Bahia, Brazil (Cunha Lima, 2008).
Free and bound ferulic trolled trial on specifc antioxidant supplementation was acid represent the major component in all cases cheap kamagra effervescent 100 mg without a prescription, followed insufcient to prove the efectiveness of each of the vitamin by p-coumaric acid purchase kamagra effervescent 100 mg with amex, sinapic acid cheap kamagra effervescent 100mg free shipping, and cafeic acid order 100mg kamagra effervescent otc. However, supplements in preventing or treating cardiovascular disease hydroxycinnamicacidshavebeenfoundtobemoreabundant . To date, more information is needed to clarify the rela- in red orange than in blond juices. Ferulic acids and cafeic tion between the intake of single carotenoids, and the risk of acidareamongthemoststudiedhydroxycinnamicacids heart diseases. As a component of lignin, ferulic acid is Due to the incapacity to synthesize vitamin C, humans a precursor in the manufacture of other aromatic compounds. It is found in all plants because Oxidative Medicine and Cellular Longevity 7 it is a key intermediate in the biosynthesis of lignin, one of the  A. The cafeic acid phenethyl mechanism of the antioxidant properties of cyanidin-3-O- - ester has been found to be a potent free radical scavenger glucopyranoside, Free Radical Research,vol. Herbert,Horticultural Varieties ischemia/reperfusion injury , cerebral damage induced of Citrus,1967. Saija, Antioxidant efectiveness as infuenced by phenolic content of fresh orange juices, Journal of Agricul- anti-infammatory action seems to depend on its efect on tural and Food Chemistry,vol. A synergic inhibits fat accumulation in mice, International Journal of action between organic farming and social activities may Obesity,vol. Program in Neuropharmacology, University of Flavonoid composition of citrus juices, Molecules,vol. Evans, The compositional characterisation and antioxidant activity of fresh juices from sicilian sweet orange (Citrus sinensis L. Yeh, Hesperidin inhibited acetaldehyde-induced matrix mental myocardial ischemic rats, Redox Report,vol. Dugo, cell lines: relationship between structure and activity, Melano- Determination of anthocyanins in blood orange juices by ma Research,vol. Matlack, observations on the red color of the blood and Melan-a melanocyte cell lines: infuence of the sequential orange, Plant Physiology,vol. Stevens, Vitamins C and E: benefcial in carotenoid content and biosynthetic gene expression in juice efects from a mechanistic perspective,Free Radical Biology and sacs of four orange varieties (Citrus sinensis) difering in fesh Medicine, vol. Buettner, The pecking order of free radicals and antioxi- cine and Pharmacotherapy, vol. Frei, Human neutrophils oxidize low-density women, European Journal of Epidemiology,vol. Mecocci, Plasma carotenoid and malondialdehyde levels in Trombosis, and Vascular Biology,vol. Carson, Routine vitamin supplementation orange juices, Journal of Agricultural and Food Chemistry,vol. Parlakpinar, endhi, Chemopreventive potential of ferulic acid in 7,12-dim- and A. Acet, Efects of cafeic acid phenethyl ester on cerebral ethylbenz[a]anthracene-induced mammary carcinogenesis in cortex: structural changes resulting from middle cerebral artery Sprague-Dawley rats, European Journal of Pharmacology,vol. Hakverdi, Cafeic acid phenethyl ester suppresses oxidative stress in Escherichia coli-induced pyelonephritis in rats, Molec- ular and Cellular Biochemistry,vol. Comlekci, Protective efects of melatonin and cafeic acid phenethyl ester against retinal oxida- tive stress in long-term use of mobile phone: a comparative study, Molecular and Cellular Biochemistry,vol. Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Visceraladiposetissueisamainsourceof deteriorating multiple organ function, leading to aging. Perturbation of the redox signaling generation and endothelial dysfunction through upregula- due to oxidative stress deteriorates endothelial function and tion of Nox, leading to insulin resistance or type 2 diabetes promotes atherosclerosis. The Diverse benefts of astaxanthin in the clinical arena, present review will discuss the issue as to why general antiox- with excellent safety and tolerability, have been extensively idants have failed to provide appreciable antiatherosclerotic reviewed . It appears that astaxanthin clinical success efects, and how the site-specifc antioxidative therapy exerts extends beyond protection against oxidative stress and benefcial efects on the cardiovascular system. Nevertheless, larger sized randomized controlled trials for subjects with lifestyle-related diseases are required 2. Effects of General Antioxidants on tine use of antioxidants for treatment of these diseases. This Ischemic Tolerance is because no appreciable benefts have been demonstrated in multiple clinical trials that employed general antioxidants. It may be argued that more that a brief period of repetitive cardiac ischemia/reperfusion than one antioxidant is required for clinical efectiveness. It is also possible that antioxidants or by-products may and inhibition of glycogen synthase kinase-3 . Nox2 to heart failure from physiological adaptation against pres- phox also known as gp91 was originally found in phagocytes sure overload to the heart. Nox1, which is the frst homolog of Nox2, is systemic infammation and oxidative stress . Conversely, Ray in the cardiovascular system and the visceral adipose tissue et al. Tese fndings indicate that the use of nonselective Nox inhibitors is not suitable for ameliorating 4. Because atheroscle- oxidative stress in the cardiovascular system and provides rosis is facilitated by dyslipidemia in conjunction with oxida- a basis for employing specifc inhibitors that block only tive stress, numerous studies have investigated relative contri- inducible Nox. In this study, while vitamin E and probucol were efec- key to promote endothelial dysfunction and hypertension tive in reducing several indices of oxidative stress including [31, 32]. It appears that in this combined model of that is incorporated into the intima of the blood vessel. Anumberofstudiesshowthatincreased cally encountered in the heart afer percutaneous coro- physical activity reduces oxidative stress. Tese studies suggest that exercise promotes atheroprotection possibly by reducing that anticytokine therapy afer reperfusion may be efective or preventing oxidative stress and infammation through in ameliorating reperfusion injury by preventing activation at least two distinct mechanisms. The antiatherosclerotic efect of allop- evidence suggests that serum uric acid is an important and urinol has also been reported in clinical studies for patients independent risk factor for cardiovascular and renal disease, with a variety of cardiovascular risk factors. The level of uric acid in the blood is increased with endothelial function in diabetic normotensive patients . Similar Oxidative Medicine and Cellular Longevity 5 fndings were reported by a number of other investigators factors [10, 69, 70]. Terefore, of allopurinol prevention of myocardial reperfusion injury any interventions against oxidative stress to endothelial cells seems to be provoked by protection of endothelial cells such as lifestyle modifcation, especially calorie restriction from oxidative stress. The cardioprotective efect of red wine has to involve redox signaling through mild uncoupling and been attributed to antioxidants present in the polyphenol membrane depolarization of mitochondria that feedbacks to fraction. It has been demonstrated resveratrol, catechin, epicatechin, and proanthocyanidins. I, and inhibited the mitochondrial apoptotic cascade leading to neuronal cell death in the hippocampus following status epilepticus . However, recent studies have shown that process results in a futile cycle and dissipation of oxidation chronic rosiglitazone administration is associated with an energy as heat. Otani, Oxidative stress as pathogenesis of cardiovascular risk associated with metabolic syndrome, Antioxidants & Redox Signaling,vol. Wiswedel, Beta-carotene cleavage products tem in the pathogenesis of atherosclerosis, Journal of Medical induce oxidative stress in vitro by impairing mitochondrial Investigation,vol. Murphy,Aredox- growth factor-beta1 in hypertensive rats, Molecular and Cellu- based mechanism for cardioprotection induced by ischemic lar Biochemistry,vol. Risks and consequences in the Normative reperfusion-induced arrhythmias in the rat. A novel signal transduction mech- regulation and relevance for cardiovascular pathophysiology, anism for transcellular communication, Hypertension,vol. Kirwan, Efects of exercise and caloric nitrate tolerance, Circulation Research,vol. Suliman, Mitochondrial tran- in regulation of mitochondrial energetics and calcium trans- scription factor A induction by redox activation of nuclear port, Circulation Research, vol.