Instruct: Given a question, retrieve relevant passages that answer the question.
Query: digoxin
This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003. In the case of all approved agents the time frame has been extended to include the 251/2 years from 01/1981 to 06/2006 for all diseases worldwide and from 1950 (earliest so far identified) to 06/2006 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a "natural product mimic" or "NM" to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 155 small molecules, 73% are other than "S" (synthetic), with 47% actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the antiinfective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore we consider that this area of natural product research should be expanded significantly.
INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors are the first line drugs for treatment of erectile dysfunction. Sildenafil (Viagra(R)), tadalafil (Cialis(R)), and vardenafil (Levitra(R)) are from the same class of drugs that inhibit PDE5. Transient visual symptoms such as change in color perception and increased light sensitivity are well-known adverse effects of these drugs and occur in 3-11% of sildenafil users. Vision-threatening (serious) ocular complications, such as nonarteritic ischemic optic neuropathy and cilio-retinal artery occlusion have rarely been reported in PDE5 inhibitor users. AIMS: To highlight and analyze the most recently published case literature on serious ocular complications of PDE5 inhibitors. METHODS: Search of the peer-reviewed English literature was conducted using Medline. The following databases also were searched: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult. The causality assessment of the reported adverse drug reactions was analyzed by applying both the World Health Organization (WHO) Probability Scale and the criteria utilized by the National Registry of Drug-Induced Ocular Side Effects. MAIN OUTCOME MEASURES: To scientifically and objectively find out if PDE5 inhibitors are associated with vision-threatening ocular complications. RESULTS: Eight case reports of serious PDE5 inhibitor-associated ocular complications were identified since January 2006 until February 2011. Case reports included cases of anterior and posterior nonarteritic ischemic optic neuropathy, central retinal vein occlusion, cilio-retinal artery occlusion, acute angle closure glaucoma and optic atrophy after sildenafil use. CONCLUSION: There is lack of conclusive evidence to indicate a direct cause-effect relationship between PDE5 inhibitor use and vision-threatening ocular events. Men who use PDE5 inhibitors appear to suffer vision-threatening complications at the same frequency as the general population. However, minor visual adverse effects occur in 3-11% of users and they are transient and reversible. © 2011 International Society for Sexual Medicine.
Ciguatera is a type of food poisoning associated with the consumption of contaminated marine fish. We report two cases in which painful ejaculation in an affected male and dyspareunia in an unaffected female following her partner's ejaculation suggest the sexual transfer of the responsible agent, ciguatoxin (CTX). Immunoassay of semen samples for CTX were not diagnostic, but the sensitivity and timing of the test employed may have precluded detection of small quantities of the toxin. We conclude that CTX may be present in the semen of men affected with ciguatera toxicity and be capable of producing symptomatology in both males and females during sexual intercourse.
Legumes and the polyphenolic compounds present in them have gained a lot of interest due to their beneficial health implications. Dietary polyphenolic compounds, especially flavonoids, exert antioxidant properties and are potent inhibitors of xanthine oxidase (XO) activity. XO is the main contributor of free radicals during exercise but it is also involved in pathogenesis of several diseases such as vascular disorders, cancer and gout. In order to discover new natural, dietary XO inhibitors, some polyphenolic fractions and pure compounds isolated from two legume plant extracts were tested for their effects on XO activity. The fractions isolated from both Vicia faba and Lotus edulis plant extracts were potent inhibitors of XO with IC50 values range from 40–135 µg/mL and 55–260 µg/mL, respectively. All the pure polyphenolic compounds inhibited XO and their Ki values ranged from 13–767 µM. Ten of the compounds followed the non competitive inhibitory model whereas one of them was a competitive inhibitor. These findings indicate that flavonoid isolates from legume plant extracts are novel, natural XO inhibitors. Their mode of action is under investigation in order to examine their potential in drug design for diseases related to overwhelming XO action.
Food, especially dairy products, meat, and fish, is the primary source of environmental exposure to dioxins in the general population. Little data exists on dioxin levels in the popular and widely consumed "fast foods". Data presented in a previously published pilot study was limited to measuring only the levels of dioxins and dibenzofurans in three types of U.S. fast food. This study adds to the previous paper by presenting data, in addition to dioxins and dibenzofurans, on the closely related dioxin-like polychlorinated biphenyls (PCBs), and the persistent metabolite of DDT, 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (DDE), in four types of popular U.S. fast food. These include McDonald's Big Mac Hamburger, Pizza Hut's Personal Pan Pizza Supreme, Kentucky Fried Chicken (KFC) three piece original recipe mixed dark and white meat luncheon package, and Häagen-Daz chocolate-chocolate chip ice cream. Dioxin plus dibenzofuran dioxin toxic equivalents (TEQ) ranged from 0.03 to 0.28 TEQ pg/g wet or whole weight for the Big Mac, from 0.03 to 0.29 for the Pizza, from 0.01 to 0.31 for the KFC, and from 0.03 to 0.49 TEQ pg/g for the ice cream. Daily TEQ consumption per kilogram body weight (kg/BW), assuming an average 65 kg adult and a 20 kg child, from one serving of each of these fast food ranged between 0.046 and 1.556 pg/kg in adults whereas in children the values were between 0.15 and 5.05 pg/kg. Total measured PCDD/Fs in the Big Mac, Personal Pan Pizza, KFC, and the Häagen-Daz ice cream varied from 0.58 to 9.31 pg/g. Measured DDE levels in the fast foods ranged from 180 to 3170 pg/g. Total mono-ortho PCB levels ranged up to 500 pg/g or 1.28 TEQ pg/g for the KFC and for di-ortho PCBs up to 740 pg/g or 0.014 TEQ pg/g for the pizza sample. Total PCB values in the four samples ranged up to 1170 pg/g or 1.29 TEQ pg/g for the chicken sample.
Ciguatera is an important form of human poisoning caused by the consumption of seafood. The disease is characterised by gastrointestinal, neurological and cardiovascular disturbances. In cases of severe toxicity, paralysis, coma and death may occur. There is no immunity, and the toxins are cumulative. Symptoms may persist for months or years, or recur periodically. The epidemiology of ciguatera is complex and of central importance to the management and future use of marine resources. Ciguatera is an important medical entity in tropical and subtropical Pacific and Indian Ocean regions, and in the tropical Caribbean. As reef fish are increasingly exported to other areas, it has become a world health problem. The disease is under-reported and often misdiagnosed. Lipid-soluble, polyether toxins known as ciguatoxins accumulated in the muscles of certain subtropical and tropical marine finfish cause ciguatera. Ciguatoxins arise from biotransformation in the fish of less polar ciguatoxins (gambiertoxins) produced by Gambierdiscus toxicus, a marine dinoflagellate that lives on macroalgae, usually attached to dead coral. The toxins and their metabolites are concentrated in the food chain when carnivorous fish prey on smaller herbivorous fish. Humans are exposed at the end of the food chain. More than 400 species of fish can be vectors of ciguatoxins, but generally only a relatively small number of species are regularly incriminated in ciguatera. Ciguateric fish look, taste and smell normal, and detection of toxins in fish remains a problem. More than 20 precursor gambiertoxins and ciguatoxins have been identified in G. toxicus and in herbivorous and carnivorous fish. The toxins become more polar as they undergo oxidative metabolism and pass up the food chain. The main Pacific ciguatoxin (P-CTX-1) causes ciguatera at levels=0.1 microg/kg in the flesh of carnivorous fish. The main Caribbean ciguatoxin (C-CTX-1) is less polar and 10-fold less toxic than P-CTX-1. Ciguatoxins activate sodium ion (Na ) channels, causing cell membrane excitability and instability. Worldwide coral bleaching is now well documented, and there is a strong association between global warming and the bleaching and death of coral. This, together with natural environmental factors such as earthquakes and hurricanes, and man-made factors such as tourism, dock construction, sewage and eutrophication, may create more favourable environments for G. toxicus. While low levels of G. toxicus are found throughout tropical and subtropical waters, the presence of bloom numbers is unpredictable and patchy. Only certain genetic strains produce ciguatoxins, and environmental triggers for increasing toxin production are unknown.
Hyperphosphatemia and hyperparathyroidism, frequently observed in patients with endstage renal disease, are associated with renal osteodystrophy, organ calcification, cardiovascular disease and sudden death. Restriction of dietary protein and phosphorus is beneficial in slowing the progression of renal failure. Dietary phosphorus restriction must be prescribed at all stages of renal failure in adults. It may be achieved by decreasing protein intake and avoiding foods rich in phosphorus. An average of 60-80% of the phosphorus intake is absorbed in the gut in dialysis patients. If phosphate binders are employed, the phosphorus absorbed from the diet may be reduced to 40%. Conventional hemodialysis with a high-flux, high-efficiency dialyzer removes approximately 30 mmol (900 mg) phosphorus during each dialysis performed three times weekly. Therefore, 750 mg of phosphorus intake should be the critical value above which a positive balance of phosphorus may occur. This value corresponds to a protein diet of 45-50 g/day or 0.8 g/kg body weight/day for a 60 kg patient. Target levels should become 9.2-9.6 mg/dl for calcium, 2.5-5.5 mg/dl for phosphorus, <55 mg2/dl2 for the calcium-phosphorus product, and 100-200 pg/ml for intact parathyroid hormone.
During the last few years, there has been increasing interest in buccal epithelial cells for cytogenetic evaluation of different materials. In the present study, the use of these cells and peripheral lymphocytes for cytogenetic evaluation of chlorhexidine digluconate (CHX) with comet assay (single cell gel electrophoresis, or SCGE) is reported. This technique detects DNA strand breaks in individual cells in alkaline conditions. Thirteen volunteers were requested to rinse their mouths with 0.12% CHX solution for 18 days. Buccal epithelial cells and peripheral blood lymphocytes were obtained from all participants at baseline and the end of the experimental period. One hundred cells per subject were analysed for the DNA damage. A statistical increase was observed in the damaged buccal and blood cells after the CHX application. The mean grade of damage in buccal cells was statistically different from that in blood cells. Due to minimal absorption of chlorhexidine into the tissues and low concentrations of free chlorhexidine in the oral cavity, the DNA damage produced by chlorhexidine in lymphocytes was lower than in buccal epithelial cells. As chlorhexidine does not accumulate in the body, the frequencies of DNA damage could be transient. Detected DNA damage after CHX use might be the indication of an earlier effect, before DNA repair begins, and could be reversible.
A streptomycete was isolated from an Easter Island soil sample and found to inhibit Candida albicans, Microsporum gypseum and Trichophyton granulosum. The antibiotic-producing microorganism was characterized and identified as Streptomyces hygroscopicus. The antifungal principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named rapamycin. Rapamycin is mainly active against Candida albicans; minimum inhibitory concentration against ten strains ranged from 0.02 to 0.2 mug/ml. Its apparent activity against Microsporum gypseum and Trichophyton granulosum is lower because of its instability in culture media on prolonged incubation required by these fungi. No activity was observed against gram-positive and gram-negative bacteria. Acute toxicity in mice is low.
In a group of patients dying suddenly from ischemic heart disease, the uninfarcted heart muscle contained significantly lower concentrations of magnesium, iron, and potassium and a significantly higher concentration of calcium than the heart muscle from a group of normal controls and a group of patients dying more than three months after a coronary thrombosis. The late death group had significantly lower concentrations of manganese and copper than the normal group, and a slight decrease in magnesium concentration which was probably significant. There was no significant difference in the sodium concentration between the three groups. The results are discussed in relation to the increased death rate from ischemic heart disease in areas with soft drinking water, and possible dietary deficiencies in mineral salts.
Reactive oxygen species produced during vigorous exercise may permeate into cell nuclei and induce oxidative DNA damage, but the supporting evidence is still lacking. By using a 42 km marathon race as a model of massive aerobic exercise, we demonstrated a significant degree of unrepaired DNA base oxidation in peripheral immunocompetent cells, despite a concurrent increase in the urinary excretion of 8-hydroxy-2'-deoxyguanosine. Single cell gel electrophoresis with the incorporation of lesion-specific endonucleases further revealed that oxidized pyrimidines (endonuclease III-sensitive sites) contributed to most of the postexercise nucleotide oxidation. The oxidative DNA damage correlated significantly with plasma levels of creatinine kinase and lipid peroxidation metabolites, and lasted for more than 1 week following the race. This phenomenon may be one of the mechanisms behind the immune dysfunctions after exhaustive exercise.
INTRODUCTION: This case report describes a patient who developed rhabdomyolysis temporally associated with the use of a mislabeled acai berry dietary supplement. METHODS AND RESULTS: The authors describe a 22-year-old man presenting with rhabdomyolysis approximately 2 weeks after starting a weight-loss dietary supplement. His medical history was significant only for hypertension treated with amlodipine. The diagnosis of rhabdomyolysis was confirmed (creatine kinase, 84,000 IU/L, positive urine myoglobin) with other potential causes ruled out. The signs and symptoms of the patient gradually resolved and he was discharged on hospital day 5. Assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 3, indicating a possible relationship between the supplement and rhabdomyolysis. Although the product was labeled and promoted as containing acai berry and additional ingredients, there was no acai berry found on analysis. CONCLUSION: Clinicians should be aware that all dietary supplements may vary in uniformity and contain unknown contaminants.
In the early 1970s, aluminium toxicity was first implicated in the pathogenesis of clinical disorders in patients with chronic renal failure involving bone (renal osteomalacia) or brain tissue (dialysis encephalopathy). Before that time the toxic effects of aluminium ingestion were not considered to be a major concern because absorption seemed unlikely to occur. Meanwhile, aluminium toxicity has been investigated in countless epidemiological and clinical studies as well as in animal experiments and many papers have been published on the subject. It is now commonly acknowledged that aluminium toxicity can be induced by infusion of aluminium-contaminated dialysis fluids, by parenteral nutrition solutions, and by oral exposure as a result of aluminium-containing pharmaceutical products such as aluminium-based phosphate binders or antacid intake. Over-the-counter antacids are the most important source for human aluminium exposure from a quantitative point of view. However, aluminium can act as a powerful neurological toxicant and provoke embryonic and fetal toxic effects in animals and humans after gestational exposure. Despite these facts, the patient information leaflets from European antacids that are available OTC show substantial differences regarding warnings from aluminium toxicity. It seems advisable that all patients should receive the same information on aluminium toxicity from patient information leaflets, in particular with regard to the increased absorption through concomitant administration with citrate-containing beverages and the use of such antacids during pregnancy.
Ilex paraguariensis dried and minced leaves are made into a brewed tea, prepared in a sui generis manner by large populations in South America, having evolved from a tea drunk by the Guarani ethnic group to a beverage that has a social and almost ritualistic role in some South American modern societies. It is used both as a source of caffeine, in lieu or in parallel with tea and coffee, but also as a therapeutic agent for its alleged pharmacological properties. Although with some exceptions, research on biomedical properties of this herb has had a late start and strongly lags behind the impressive amount of literature on green tea and coffee. However, in the past 15 years, there was a several-fold increase in the literature studying Ilex paraguariensis properties showing effects such as antioxidant properties in chemical models and ex vivo lipoprotein studies, vaso-dilating and lipid reduction properties, antimutagenic effects, controversial association with oropharyngeal cancer, anti-glycation effects and weight reduction properties. Lately, promising results from human intervention studies have surfaced and the literature offers several developments on this area. The aim of this review is to provide a concise summary of the research published in the past three years, with an emphasis on translational studies, inflammation and lipid metabolism. Ilex paraguariensis reduces LDL-cholesterol levels in humans with Ilex paraguariensis dyslipoproteinemia and the effect is synergic with that of statins. Plasma antioxidant capacity as well as expression of antioxidant enzymes is positively modulated by intervention with Ilex paraguariensis in human cohorts. A review on the evidence implicating Ilex paraguariensis heavy consumption with some neoplasias show data that are inconclusive but indicate that contamination with alkylating agents during the drying process of the leaves should be avoided. On the other hand, several new studies confirm the antimutagenic effects of Ilex paraguariensis in different models, from DNA double breaks in cell culture models to mice studies. Novel interesting work has emerged showing significant effect on weight reduction both in mice and in rat models. Some mechanisms involved are inhibition of pancreatic lipase, activation of AMPK and uncoupling of electron transport. Intervention studies in animals have provided strong evidence of anti-inflammatory effects of Ilex paraguariensis, notably protecting cigarette-induced lung inflammation acting on macrophage migration and inactivating matrix-metalloproteinase. Research on the effects of Ilex paraguariensis in health and disease has confirmed its antioxidant, anti-inflammatory, antimutagenic and lipid-lowering activities. Although we are still waiting for the double-blind, randomized prospective clinical trial, the evidence seems to provide support for beneficial effects of mate drinking on chronic diseases with inflammatory component and lipid metabolism disorders. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Background Epidemiologic studies suggest that there may be an association between environmental exposure to persistent organic pollutants (POPs) and diabetes. Objective The aim of this study was to test the hypothesis that residential proximity to POP-contaminated waste sites result in increased rates of hospitalization for diabetes. Methods We determined the number of hospitalized patients 25–74 years of age diagnosed with diabetes in New York State exclusive of New York City for the years 1993–2000. Descriptive statistics and negative binomial regression were used to compare diabetes hospitalization rates in individuals who resided in ZIP codes containing or abutting hazardous waste sites containing POPs (“POP” sites); ZIP codes containing hazardous waste sites but with wastes other than POPs (“other” sites); and ZIP codes without any identified hazardous waste sites (“clean” sites). Results Compared with the hospitalization rates for diabetes in clean sites, the rate ratios for diabetes discharges for people residing in POP sites and “other” sites, after adjustment for potential confounders were 1.23 [95% confidence interval (CI), 1.15–1.32] and 1.25 (95% CI, 1.16–1.34), respectively. In a subset of POP sites along the Hudson River, where there is higher income, less smoking, better diet, and more exercise, the rate ratio was 1.36 (95% CI, 1.26–1.47) compared to clean sites. Conclusions After controlling for major confounders, we found a statistically significant increase in the rate of hospitalization for diabetes among the population residing in the ZIP codes containing toxic waste sites.
Caffeine is a natural alkaloid methylxanthine that is found in various plants such as coffee or tea. Symptoms of a severe overdose may present with hypokalemia, hyponatremia, ventricular arrhythmias, hypertension followed by hypotension, respiratory failure, seizures, rhabdomyolysis, ventricular fibrillation and finally circulatory collapse. A 21-year-old woman called for the ambulance herself soon after the ingestion of about 10,000 mg of caffeine. At the arrival of the ambulance, the patient went into cardiac arrest almost immediately. After a total resuscitation period of 34 min including seven counter-shocks and 2 mg epinephrine, the patient was stable enough to be transferred to the hospital. The patient soon went into VF again and received two more counter-shocks and 1 mg epinephrine and finally an intravenous bolus dose of 300 mg amiodarone. The initial arterial blood gas showed pH at 6.47, lactate at 33 mmol/l and potassium level at 2.3 mmol/l. Unfortunately, no blood samples for caffeine analysis were taken. Three days after hospital admission, the patient developed myoclonus, which did not respond to medical treatment. Excessive intake of caffeine may produce arrhythmias and pronounced hypokalemia and ensuing ventricular fibrillation. In case of counter-shock-resistant VF, it can be necessary to give an early loading dose of amiodarone. Furthermore, it may be beneficial to replace the potassium as early as possible. Epinephrine and buffer solutions used during resuscitation may further decrease blood potassium levels and should be administrated cautiously. Epinephrine can be replaced by other vasopressor drugs, such as vasopressin without effects on beta-receptors.
BACKGROUND: Exposure to over-the-counter (OTC) ibuprofen and other OTC non-steroidal anti-inflammatory drugs (NSAIDs) is substantial. Although the literature on gastrointestinal (GI) safety of NSAID therapy is extensive, the risk profiles of OTC and prescription dosing are seldom separated, and few studies provide risks specific to OTC ibuprofen. OBJECTIVE: To conduct a literature review to evaluate the risk of GI bleeding events related to OTC ibuprofen use. METHODS: Published clinical trials, observational studies, and meta-analyses of OTC ibuprofen use, defined as up to 1200 mg/day or stated as 'over the counter,' reporting endpoints of incidence rates and proportions of GI bleeding events (e.g., GI bleeding-related hospitalizations and deaths) were identified via MEDLINE through 2010. Data from these studies were summarized. RESULTS: Twenty studies (nine observational, ten clinical trials, one meta-analysis) reporting incidence rates and proportions of a GI bleeding-related event associated with OTC or OTC-specific doses of ibuprofen were included. The frequency of a GI-related hospitalization was <0.2% for patients on OTC-comparable doses. Incidence rates among those using OTC-comparable doses ranged from 0 to 3.19 per 1000 patient-years. The incidence of a GI bleeding-related event increased with age and the use of concomitant medications, and there was a general, though not always statistically significant, ibuprofen dose-response relationship. The relative risk of any GI bleeding-related event ranged from 1.1 to 2.4 for users of OTC-specific doses of ibuprofen compared to non-users. CONCLUSIONS: Studies reported low incidence of GI bleeding events with use of OTC ibuprofen. Few published studies that specifically investigated OTC ibuprofen use were identified. Varying methodologies and definitions of exposure and outcomes prevented direct comparison of many results. Only studies that used the methods herein described were identified. Further research evaluating the risk of GI bleeding events in patients taking OTC-specific ibuprofen use may be useful.
Dry-eye syndrome (DES) is a multifactorial disease affecting millions of individuals worldwide. Various factors, including age, hormonal status, genetics, sex, immune status, innervation status, nutrition, pathogens, and environmental stress, can alter the cellular and molecular structure or function of components of the ocular surface system. The resulting imbalance increases susceptibility to desiccation and epithelial damage, leading to a vicious circle in which inflammation amplifies and sustains further damage by chronic deregulation of the system. Lubricating agents and steroids have been used as treatment options. However, as the causes of the disease become better elucidated, the more chemically complex cyclosporine A has become an increasingly useful treatment option and in the United States is currently the only Food and Drug Administration (FDA)-approved prescription drug for the treatment of dry eye. The safety and efficacy of cyclosporine have been shown in numerous studies.
OBJECTIVE: Low-level exposure to some persistent organic pollutants (POPs) has recently become a focus because of their possible link with the risk of diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional associations of the serum concentrations of POPs with diabetes prevalence were investigated in 2,016 adult participants in the National Health and Nutrition Examination Survey 1999-2002. Six POPs (2,2',4,4',5,5'-hexachlorobiphenyl, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, oxychlordane, p,p'-dichlorodiphenyltrichloroethane, and trans-nonachlor) were selected, because they were detectable in >or=80% of participants. RESULTS: Compared with subjects with serum concentrations below the limit of detection, after adjustment for age, sex, race and ethnicity, poverty income ratio, BMI, and waist circumference, diabetes prevalence was strongly positively associated with lipid-adjusted serum concentrations of all six POPs. When the participants were classified according to the sum of category numbers of the six POPs, adjusted odds ratios were 1.0, 14.0, 14.7, 38.3, and 37.7 (P for trend < 0.001). The association was consistent in stratified analyses and stronger in younger participants, Mexican Americans, and obese individuals. CONCLUSIONS: There were striking dose-response relations between serum concentrations of six selected POPs and the prevalence of diabetes. The strong graded association could offer a compelling challenge to future epidemiologic and toxicological research.
ESC is to create an inventory of cardiovascular disease registries and a task force on data standardization
The US Environmental Protection Agency's 2004 Dioxin Reassessment included a characterization of background exposures to dioxin-like compounds, including an estimate of an average background intake dose and an average background body burden. These quantities were derived from data generated in the mid-1990s. Studies conducted in the 2000s were gathered in an attempt to update the estimates generated by the Reassessment. While these studies suggest declines in the average background dose and body burden, a precise quantification of this decline, much less a conclusion that a decline has indeed occurred, cannot be made because of the inconsistency of study design and data sources, and the treatment of non-detects in the generation of congener average concentrations. The average background intake of the Reassessment was 61.0 pg TEQ/day, and using more current data, the average background intake was 40.6 pg TEQ/day. The average body burden from the surveys in the mid-1990s was 22.9 pg TEQ/g lipid weight (pg/g lwt). More recent blood concentration data, from NHANES 2001/2, suggest an adult average at 21.7 pg/g TEQ lwt. These TEQ values include the 17 dioxin and furan congeners and 3 coplanar PCBs, and were generated substituting ND=(1/2)DL or ND=DL/sq rt (2). Results are provided for ND=0 and analyses conducted to evaluate the impacts of this substitution. A more detailed examination of beef and pork data from similarly designed national statistical surveys show that declines in pork are statistically significant while the beef concentrations appeared to have remained constant between the time periods.
Chlorhexidine (CHX) is one of the most commonly prescribed antiseptic agents in the dental field. It has a long-lasting antibacterial activity with a broad-spectrum of action and it has been shown to reduce plaque, gingival inflammation and bleeding. Its use is considered a powerful adjuvant to mechanical oral hygiene (brushing and flossing), especially in those cases in which it cannot be performed correctly. Available as mouthwash, gel, aerosol, spray and disks, CHX is considered a safe compound, with minimal and transitory local and systemic side effects. Data support its periodic use as an adjuvant to normal brushing and flossing in subjects unable to maintain proper oral hygiene due to physical and/or mental impairment, or lack of motivation, or decreased salivary rate. CHX is also a useful alternative to mechanical oral hygiene procedures in those cases in which they are contraindicated, e.g. after a surgical procedure, or as a preoperative rinse before procedures in which use of a dental dam is not possible. The aim of this article is to offer a complete review of literature regarding the characteristics, the applications and the problems associated with the use of chlorhexidine in the dental field.
The pharmacology, clinical efficacy, adverse effects, drug interactions, and place in therapy of bitter melon are described. Bitter melon (Momordica charantia) is an alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus. Components of bitter melon extract appear to have structural similarities to animal insulin. Antiviral and antineoplastic activities have also been reported in vitro. Four clinical trials found bitter melon juice, fruit, and dried powder to have a moderate hypoglycemic effect. These studies were small and were not randomized or double-blind, however. Reported adverse effects of bitter melon include hypoglycemic coma and convulsions in children, reduced fertility in mice, a favism-like syndrome, increases in gamma-glutamyltransferase and alkaline phosphatase levels in animals, and headaches. Bitter melon may have additive effects when taken with other glucose-lowering agents. Adequately powered, randomized, placebo-controlled trials are needed to properly assess safety and efficacy before bitter melon can be routinely recommended. Bitter melon may have hypoglycemic effects, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring.
Cisapride is a substituted benzamide compound that stimulates motor activity in all segments of the gastrointestinal tract by enhancing the release of acetylcholine from the enteric nervous system. Cisapride is administered orally in the treatment of gastro-oesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction syndromes and chronic constipation. In gastro-oesophageal reflux disease in both adults and children, cisapride provides symptomatic improvement and mucosal healing. Long term treatment with cisapride is effective in the prevention of relapse of oesophagitis. Cisapride improves gastric emptying rates and improves symptoms in patients with gastroparesis of various origins. Unlike domperidone and metoclopramide, long term administration of cisapride seems to result in persistently enhanced gastric emptying. Cisapride is also effective in improving symptoms in patients with functional dyspepsia. In comparative studies in patients with functional dyspepsia, cisapride was at least as effective as metoclopramide, domperidone, clebopride, ranitidine and cimetidine. Cisapride increases stool frequency and reduces laxative consumption in patients with idiopathic constipation. Severe cases of slow transit constipation seem refractory to cisapride. Clinical studies also indicate that cisapride might be effective in the treatment of chronic intestinal pseudo-obstruction, postoperative ileus, peptic ulcer and irritable bowel syndrome. Further clinical studies are warranted to define the role of cisapride in these conditions. The dosage of cisapride ranges from 5mg 3 times daily to 20mg twice daily. Cisapride is generally well tolerated, both during short and long term treatment. In children, cisapride is also well tolerated in doses of 0.2 to 0.3 mg/kg, 3 to 4 times daily.(ABSTRACT TRUNCATED AT 250 WORDS)
A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its ability to alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatment dosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study. For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased -3.67 +/- 1.56, -7.33 +/- 1.18, and -6.88 +/- 1.43 (mean +/- SE, P = .100, < .001, and < .001 compared to baseline), the Quality of Life score (QOL score) improved by -0.71 +/- 0.23, -1.48 +/- 0.24, and -1.75 +/- 0.25 (mean +/- SE, P = .163 and .012 compared to placebo and P = .103, < .001, and < .001 compared to baseline), and the number of subjects whose LUTS grade changed from "moderate/severe" to "mild" increased by three, six, and 10 (P = .188, .032, and .012 compared to baseline). Maximum urinary flows insignificantly increased 0.43 +/- 1.57, 1.86 +/- 1.08, and 2.7 +/- 1.93 mL/second (mean +/- SE, no statistical significance reached), and postvoiding urine volume decreased insignificantly by -29.4 +/- 20.46, -19.2 +/- 16.91, and -55.62 +/- 36.45 mL (mean +/- SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOL score were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lignan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of commonly used intervention agents of alpha1A-adrenoceptor blockers and 5alpha-reductase inhibitors.