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Sample records for adverse renal effects

  1. Metabolic and renal adverse effects of antiretroviral therapy in HIV-infected children and adolescents.

    PubMed

    Fortuny, Clàudia; Deyà-Martínez, Ángela; Chiappini, Elena; Galli, Luisa; de Martino, Maurizio; Noguera-Julian, Antoni

    2015-05-01

    Worldwide, the benefits of combined antiretroviral (ARV) therapy in morbidity and mortality due to perinatally acquired human immunodeficiency virus infection are beyond question and outweigh the toxicity these drugs have been associated with in HIV-infected children and adolescents to date. In puberty, abnormal body fat distribution is stigmatizating and leads to low adherence to ARV treatment. The other metabolic comorbidities (mitochondrial toxicity, dyslipidemias, insulin resistance and low bone mineral density) and renal toxicity, albeit nonsymptomatic in most children, are increasingly being reported and potentially put this population at risk for early cardiovascular or cerebrovascular atherosclerotic disease, diabetes, pathologic fractures or premature renal failure in the third and fourth decades of life. Evidence from available studies is limited because of methodological limitations and also because of several HIV-unrelated factors influencing, to some degree, the development of these conditions. Current recommendations for the prevention, diagnosis, monitoring and treatment of metabolic and renal adverse effects in HIV-children and adolescents are based on adult studies, observational pediatric studies and experts' consensus. Healthy lifestyle habits (regarding diet, exercise and refraining from toxic substances) and wise use of ARV options are the only preventive tools for the majority of patients. Should abnormal findings arise, switches in one or more ARV drugs have proved useful. Specific therapies are also available for some of these comorbidities, although the experience in the pediatric age is still very scarce. We aim to summarize the epidemiological, clinical and therapeutic aspects of metabolic and renal adverse effects in vertically HIV-infected children and adolescents.

  2. Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

    PubMed

    Ko, J-L; Tsai, C-H; Liu, T-C; Lin, M-Y; Lin, H-L; Ou, C-C

    2016-08-01

    Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity.

  3. Ibuprofen-Induced Hypokalemia and Distal Renal Tubular Acidosis: A Patient's Perceptions of Over-the-Counter Medications and Their Adverse Effects.

    PubMed

    Salter, Mark D

    2013-01-01

    We highlight a case of distal renal tubular acidosis secondary to ibuprofen and codeine use. Of particular interest in this case are the patient's perception of over-the-counter (OTC) medication use, her own OTC use prior to admission, and her knowledge of adverse reactions or side effects of these medications prior to taking them.

  4. Ibuprofen-Induced Hypokalemia and Distal Renal Tubular Acidosis: A Patient's Perceptions of Over-the-Counter Medications and Their Adverse Effects

    PubMed Central

    Salter, Mark D.

    2013-01-01

    We highlight a case of distal renal tubular acidosis secondary to ibuprofen and codeine use. Of particular interest in this case are the patient's perception of over-the-counter (OTC) medication use, her own OTC use prior to admission, and her knowledge of adverse reactions or side effects of these medications prior to taking them. PMID:24829833

  5. Effect of the Obesity Epidemic on Kidney Transplantation: Obesity Is Independent of Diabetes as a Risk Factor for Adverse Renal Transplant Outcomes

    PubMed Central

    Kwan, Jennifer M.; Hajjiri, Zahraa; Metwally, Ahmed

    2016-01-01

    Background Obesity is a growing epidemic in most developed countries including the United States resulting in an increased number of obese patients with end-stage renal disease. A previous study has shown that obese patients with end-stage renal disease have a survival benefit with transplantation compared with dialysis. However, due to serious comorbidities, many centers place restrictions on the selection of obese patients for transplantation. Further, due to obese patients having an increased risk of diabetes, it is unclear whether obesity can be an independent risk, independent of diabetes for increasing adverse renal transplant outcomes. Methods To investigate the role of obesity in kidney transplantation, we used the Scientific Registry of Transplant Recipients database. After filtering for subjects that had the full set of covariates including age, gender, graft type, ethnicity, diabetes, peripheral vascular disease, dialysis time and time period of transplantation for our analysis, 191,091 subjects were included in the analyses. Using multivariate logistic regression analyses adjusted for covariates we determined whether obesity is an independent risk factor for adverse outcomes such as delayed graft function, acute rejection, urine protein and graft failure. Cox regression modeling was used to determine hazard ratios of graft failure. Results Using multivariate model analyses, we found that obese patients have significantly increased risk of adverse transplant outcomes, including delayed graft function, graft failure, urine protein and acute rejection. Cox regression modeling hazard ratios showed that obesity also increased risk of graft failure. Life-table survival curves showed that obesity may be a risk factor independent of diabetes mellitus for a shorter time to graft failure. Conclusions A key observation in our study is that the risks for adverse outcome of obesity are progressive with increasing body mass index. Furthermore, pre-obese overweight

  6. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  7. [Cardiovascular pharmacotherapy. Risks and adverse effects].

    PubMed

    Voigt, N; Heijman, J; Dobrev, D

    2014-03-01

    Adverse side effects of drugs are a significantly underestimated problem in modern medicine. In this review article, we summarize common adverse side effects of cardiovascular drugs. In particular, we highlight the factors promoting these adverse side effects in patients, including reduced hepatic or renal clearance in elderly patients that often requires dosage adjustment. Pharmacodynamic and pharmacokinetic interactions between drugs (e.g. through the cytochrome P450 system or P-glycoproteins) can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. The most prominent cardiac side effects include arrhythmias, e.g. atrioventricular (AV) block, drug-induced long-QT syndrome and torsade de pointes and altered inotropy. Non-cardiac side effects are subsequently discussed grouped by drug class. A better understanding of the risks and side effects of cardiovascular drugs is expected to reduce the mortality and morbidity associated with adverse side effects.

  8. Telithromycin: review of adverse effects.

    PubMed

    2014-11-01

    Telithromycin is a macrolide antibiotic that has been marketed since the early 2000s. It has not been shown to be more effective against any bacteria than other macrolide antibiotics. Its antibacterial activity is in no way remarkable. In early 2014, we reviewed its adverse effect profile using data from periodic safety update reports, drug regulatory agencies, and detailed published case reports. In addition to the adverse effect profile telithromycin shares with the other macrolides, it provokes several specific adverse effects: visual disturbances due to impaired accommodation; taste and smell disorders; severe liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of consciousness. Prolongation of the QT interval with standard oral doses is a worrisome adverse effect. In practice, it is better not to use telithromycin as it exposes patients to disproportionate, serious adverse effects. When treatment with a macrolide antibiotic appears necessary, it is prudent to choose a different macrolide, such as spiramycin or azithromycin, which have fewer adverse effects.

  9. Data and Safety Monitoring Board evaluation and management of a renal adverse event signal in TOPCAT.

    PubMed

    Bristow, Michael R; Sharma, Kavita; Assmann, Susan F; Linas, Stuart; Gersh, Bernard J; Grady, Christine; Rice, Madeline Murguia; Singh, Steven; Boineau, Robin; McKinlay, Sonja M; Greenberg, Barry H

    2017-04-01

    Clinical trial Data and Safety Monitoring Boards (DSMBs) have a primary obligation of ensuring study participant safety, while maintaining trial integrity. The role of DSMBs is expanding, and ideally should include post-hoc reporting of deliberative processes related to clinically important safety issues or factors that could impact on future trial designs. We describe how the TOPCAT DSMB detected, investigated, and adjudicated an unexpectedly large renal adverse event signal midway through the trial, and offer general guidelines for dealing with similar unanticipated occurrences in future trials. The detection of a greater than expected incidence of deterioration in renal function, occurring in 6.1% of patients in the spironolactone arm compared with 3.9% in the placebo arm (P = 0.009), led to an in-depth DSMB review of associated study medication withdrawals and adverse events. The trial continued uninterrupted throughout the review, which reached the conclusions that spironolactone-associated renal dysfunction did not compromise overall patient safety or interfere with a perceived efficacy signal. Although no discrete mechanism for the spironolactone-associated renal adverse event signal was identified, likely possibilities are discussed. In clinical trials, DSMBs and co-ordinating centres should have the resources to detect, investigate, and adjudicate unexpected safety issues, with goals of ensuring patient safety and preserving the potential for detection of therapeutic effectiveness. In TOPCAT, spironolactone-associated renal dysfunction emerged as a potentially trial-threatening adverse event and, although clinically important, did not lead to compromise of patient safety, trial interruption, termination, or apparent loss of treatment effectiveness.

  10. Adverse effects of statins - myths and reality.

    PubMed

    Šimić, Iveta; Reiner, Željko

    2015-01-01

    Statins reduce cardiovascular mortality and morbidity as well as cardiovascular events in patients with a very high risk of cardiovascular disease (CVD) and also in subjects with high or moderate risk by reducing the levels of low-density lipoprotein cholesterol (LDL-C). Although they are considered to be drugs with a very good safety profile, because of their wide use there are many concerns that their adverse effects might compromise their proven beneficial effects. Therefore this article reviews all the data and provides an evidence- based insight what are the proven adverse effects of statins and what are the "myths" about them. The most important side effects include myopathy and rhabdomyolysis. Another side effect is increased activity of liver tests which occurs occasionally and is reversible. However, recent studies even suggest that statin therapy can improve hepatic steatosis. It is beyond any doubt that statins do slightly increase the incidence of type 2 diabetes mellitus in people with two or more components of metabolic syndrome but the cardiovascular benefits of such a treatment by far exceed this risk. Statin therapy has also been associated with some adverse renal effects, eg. acute renal failure, but recent data suggest even a possible protective effect of these drugs on renal dysfunction. Concerns that statins might increase cancer have not been proven. On the contrary, several studies have indicated a possible benefit of these drugs in patients with different types of cancer. Early concerns about cognitive dysfunction and memory loss associated with statins use could not be proven and most recent data even suggest a possible beneficial effect of statins in the prevention of dementia. Systematic reviews and clinical guidelines suggest that the cardiovascular benefits of statins by far out-weight non-cardiovascular harms in patients with cardiovascular risk.

  11. Renal systolic time intervals derived from intra-renal artery Doppler as a novel predictor of adverse cardiac outcomes

    PubMed Central

    Lee, Wen-Hsien; Hsu, Po-Chao; Chu, Chun-Yuan; Chen, Szu-Chia; Lee, Hung-Hao; Lee, Meng-Kuang; Lee, Chee-Siong; Yen, Hsueh-Wei; Lin, Tsung-Hsien; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung; Kuo, Po-Lin; Su, Ho-Ming

    2017-01-01

    The aim of this study was to evaluate the use of renal systolic time intervals measured by electrocardiographic gated Doppler ultrasonography for predicting adverse cardiac events. This longitudinal observation study enrolled 205 patients. Renal systolic time intervals, including pre-ejection period (PEP) and ejection time (ET), and ratio of renal PEP to ET, were measured by electrocardiographic gated Doppler ultrasound. The 14 adverse cardiac events identified in this population included 9 cardiac deaths and 5 hospitalizations for heart failure during an average follow up of 30.9 months (25th–75th percentile: 30–33 months). Renal PEP (hazard ratio = 1.023, P = 0.001), renal ET (hazard ratio = 0.975, P = 0.001) and renal PEP/ET (per 0.01 unit increase, hazard ratio = 1.060, P < 0.001) were associated with poor cardiac outcomes. The addition of renal PEP/ET to a Cox model containing important clinical variables and renal resistive index further improved the value in predicting adverse cardiac events (Chi-square increase, 9.996; P = 0.002). This study showed that parameters of intra-renal hemodynamics were potential predictors of adverse cardiac outcomes. However, the generalizability of these indicators need to be investigated in future large-scale studies. PMID:28266644

  12. The interaction between fluid status and angiopoietin-2 in adverse renal outcomes of chronic kidney disease

    PubMed Central

    Chiu, Yi-Wen; Kuo, Hung-Tien; Lee, Jia-Jung; Lee, Su-Chu; Chen, Tzu-Hui; Lin, Ming-Yen; Hwang, Shang-Jyh; Kuo, Mei-Chuan; Hsu, Ya-Ling; Chen, Hung-Chun

    2017-01-01

    Background Fluid overload is not only the characteristic but also an important complication in chronic kidney disease (CKD) patients. Angiopoietin-2 (Angpt2) disturbs endothelium and vessel permeability, which may induce fluid overload. The aim of this study is to examine the interaction between fluid status and Angpt2 in adverse renal outcomes of CKD. Methods This cohort study enrolled 290 patients with CKD stages 3–5 from January 2011 to December 2011 and followed up until December 2015. Fluid status was presented as overhydration (OH) value measured by body composition monitor, while OH>1.1L was defined as fluid overload. Renal outcomes were defined as commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate < -5 ml/min/1.73 m2/y). Results During a mean follow-up of 38.6±18.3 months, 125 (43.1%) patients progressed to commencing dialysis and 99(34.7%) patients presented rapid renal function decline. All patients were stratified by OH of 1.1L and the median of circulating Angpt2. These patients with both OH>1.1L and high circulating Angpt2 were more likely to reach commencing dialysis compared to other groups. The risks for commencing dialysis and rapid renal function decline were significantly higher in patients with OH>1.1L and high circulating Angpt2 level compared to those with OH≦1.1L and low circulating Angpt2 (2.14, 1.21–3.78, P = 0.009; 4.96, 1.45–16.97, P = 0.01). There was a significant interaction between OH level and circulating Angpt2 in entering dialysis (P-interaction = 0.02). Conclusions Fluid overload and Angpt2 might have a synergistic effect on adverse renal outcomes in CKD patients. PMID:28333979

  13. Thiocolchicoside: review of adverse effects.

    PubMed

    2016-02-01

    Thiocolchicoside has long been used as a muscle relaxant, despite a lack of proven efficacy beyond the placebo effect. Its chemical structure consists of colchicine, a sugar (ose) and a sulphur-containing radical (thio), and its adverse effects are therefore likely to be similar to those of colchicine. Using the standard Prescrire methodology, we reviewed the available data on the adverse effects of thiocolchicoside. Liver injury, pancreatitis, seizures, blood cell disorders, severe cutaneous disorders, rhabdomyolysis and reproductive disorders have all been recorded in the French and European pharmacovigilance databases and in the periodic updates that the companies concerned submit to regulatory agencies. These data do not specify the frequency of the disorders nor do they identify the most susceptible patient populations. Thiocolchicoside is teratogenic in experimental animals and also damages chromosomes. Human data are limited to a follow-up of about 30 pregnant women (no major malformations) and reports of altered spermatogenesis, including cases of azoospermia. In practice, there is no justification for exposing patients to the adverse effects of thiocolchicoside. It is better to use an effective, well-known analgesic for patients complaining of muscle pain, starting with paracetamol.

  14. Adverse effects of cow's milk in infants.

    PubMed

    Ziegler, Ekhard E

    2007-01-01

    The feeding of cow's milk has adverse effects on iron nutrition in infants and young children. Several different mechanisms have been identified that may act synergistically. Probably most important is the low iron content of cow's milk. It makes it difficult for the infant to obtain the amounts of iron needed for growth. A second mechanism is the occult intestinal blood loss, which occurs in about 40% of normal infants during feeding of cow's milk. Loss of iron in the form of blood diminishes with age and ceases after 1 year of age. A third factor is calcium and casein provided by cow's milk in high amounts. Calcium and casein both inhibit the absorption of dietary nonheme iron. Infants fed cow's milk receive much more protein and minerals than they need. The excess has to be excreted in the urine. The high renal solute load leads to higher urine concentration during the feeding of cow's milk than during the feeding of breast milk or formula. When fluid intakes are low and/or when extrarenal water losses are high, the renal concentrating ability of infants may be insufficient for maintaining water balance in the face of high water use for excretion of the high renal solute. The resulting negative water balance, if prolonged, can lead to serious dehydration. There is strong epidemiological evidence that the feeding of cow's milk or formulas with similarly high potential renal solute load places infants at an increased risk of serious dehydration. The feeding of cow's milk to infants is undesirable because of cow's milk's propensity to lead to iron deficiency and because it unduly increases the risk of severe dehydration.

  15. [Finasteride adverse effects: An update].

    PubMed

    Carreño-Orellana, Néstor; Moll-Manzur, Catherina; Carrasco-Zuber, Juan Eduardo; Álvarez-Véliz, Sergio; Berroeta-Mauriziano, Daniela; Porras-Kusmanic, Ninoska

    2016-12-01

    Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

  16. Adverse effects of oral antiviral therapy in chronic hepatitis B

    PubMed Central

    Kayaaslan, Bircan; Guner, Rahmet

    2017-01-01

    Oral nucleoside/nucleotide analogues (NAs) are currently the backbone of chronic hepatitis B (CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects (i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a “Black Box” warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus (HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment. PMID:28261380

  17. Adverse effects of antihypertensive drugs.

    PubMed

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  18. The renal effects of NSAIDs in dogs.

    PubMed

    Lomas, Amy L; Grauer, Gregory F

    2015-01-01

    The quality of life for dogs with osteoarthritis can often be improved with nonsteroidal anti-inflammatory drugs (NSAIDs); however, the number of adverse drug events associated with NSAID use reported to the Federal Drug Administration Center for Veterinary Medicine is higher than that for any other companion animal drug. Of those events, adverse renal reactions are the second most reported. NSAIDs produce pharmacologic effects via inhibition of cyclooxygenase (COX), which decreases production of prostanoids. Prostaglandins are synthesized by both the COX-1 and COX-2 enzymes in the healthy kidney and influence renal blood flow, glomerular filtration rate, renin release, and Na excretion. There are important species differences in the renal expression of COX-1 and COX-2. For example, dogs have higher basal levels of COX-2 expression in the kidney compared with humans. In addition, in dogs with chronic kidney disease, an increase in COX-2 expression occurs and synthesis of prostaglandins shifts to the COX-2 pathway. For those reasons, NSAIDs that target COX-2 may be expected to adversely affect renal function in dogs, especially dogs with chronic kidney disease. The purpose of this review was to evaluate the literature to report the renal effects of NSAIDs in dogs.

  19. Prognostic indicators of adverse renal outcome and death in acute kidney injury hospital survivors

    PubMed Central

    Hamzić-Mehmedbašić, Aida; Rašić, Senija; Balavac, Merima; Rebić, Damir; Delić-Šarac, Marina; Durak-Nalbantić, Azra

    2016-01-01

    Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome. PMID:27471736

  20. Adverse effects of anabolic steroids in athletes. A constant threat.

    PubMed

    Maravelias, C; Dona, A; Stefanidou, M; Spiliopoulou, C

    2005-09-15

    Anabolic-androgenic steroids (AAS) are used as ergogenic aids by athletes and non-athletes to enhance performance by augmenting muscular development and strength. AAS administration is often associated with various adverse effects that are generally dose related. High and multi-doses of AAS used for athletic enhancement can lead to serious and irreversible organ damage. Among the most common adverse effects of AAS are some degree of reduced fertility and gynecomastia in males and masculinization in women and children. Other adverse effects include hypertension and atherosclerosis, blood clotting, jaundice, hepatic neoplasms and carcinoma, tendon damage, psychiatric and behavioral disorders. More specifically, this article reviews the reproductive, hepatic, cardiovascular, hematological, cerebrovascular, musculoskeletal, endocrine, renal, immunologic and psychologic effects. Drug-prevention counseling to athletes is highlighted and the use of anabolic steroids is must be avoided, emphasizing that sports goals may be met within the framework of honest competition, free of doping substances.

  1. Statin-Associated Muscular and Renal Adverse Events: Data Mining of the Public Version of the FDA Adverse Event Reporting System

    PubMed Central

    Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

    2011-01-01

    Objective Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. Methods After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Results Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Conclusions Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events. PMID:22205938

  2. Incidence and management of renal adverse events in patients with relapsed and/or refractory multiple myeloma treated with single-agent carfilzomib.

    PubMed

    Shah, Jatin J

    2013-12-01

    Patients with multiple myeloma (MM) frequently experience renal dysfunction owing to patient-specific risk factors, the pathophysiology of MM, and treatment-related adverse events. The presence of renal complications in patients with MM may be associated with advanced disease and is a negative prognostic factor for survival. Frequently these patients receive reduced or modified dosing regimens, which can result in under-dosing and may adversely affect treatment efficacy. Consequently, there is a need for effective therapies with favorable renal safety profiles. Carfilzomib is a selective proteasome inhibitor approved in the United States as a single agent for the treatment of relapsed and refractory MM. Safety studies have demonstrated that single-agent carfilzomib is well tolerated in patients with relapsed and/or refractory MM and concomitant renal dysfunction. This article reviews the etiology and incidence of renal adverse events in patients with MM, the renal safety profile of single-agent carfilzomib from four phase II studies in patients with relapsed and/or refractory MM, and the management of patients with MM who receive carfilzomib and are at risk for renal complications.

  3. Therapeutic effects of renal denervation on renal failure.

    PubMed

    Wang, Yutang; Seto, Sai-Wang; Golledge, Jonathan

    2013-05-01

    Sympathetic nerve activity (SNA) is increased in both patients and experimental animals with renal failure. The kidney is a richly innervated organ and has both efferent and afferent nerves. Renal denervation shows protective effects against renal failure in both animals and humans. The underlying mechanisms include a decrease in blood pressure, a decrease in renal efferent SNA, a decrease in central SNA and sympathetic outflow, and downregulation of the reninangiotensin system. It has been demonstrated that re-innervation occurs within weeks after renal denervation in animals but that no functional re-innervation occurs in humans for over two years after denervation. Renal denervation might not be renal protective in some situations including bile duct ligation-induced renal failure and ischemia/reperfusion-induced acute kidney injury. Catheter-based renal denervation has been applied to patients with both early and end stage renal failure and the published results so far suggest that this procedure is safe and effective at decreasing blood pressure. The effectiveness of renal denervation in improving renal function in patients with renal failure needs to be further investigated.

  4. The adverse effects of kava.

    PubMed

    Kava, R

    2001-03-01

    In Fiji, kava is also known as yaqona or grog. A convenient sample of 300 kava drinkers in Nadi, Lautoka, Ba and Sigatoka were studied to see whether local people in Fiji experienced side effects of kava use. Because males usually consume kava in Fiji, we approached specific groups of people and asked them to participate in the survey. To evaluate the side effects of kava consumption, we interviewed housewives of male kava drinkers regarding specific effects of kava. We interviewed these housewives during kava drinking sessions since they were usually not taking part in the kava drinking. We also interviewed employers of these kava drinkers and the market vendors in Nadi Town since they were closely involved with kava drinkers. Wives of kava users felt deprived of basic family needs due to the amount of money spent on kava. In Urban schools, 64% males and 46.2% had tried kava. The present study aims to assess the prevalence of side effects of kava usage among a community sample of kava drinkers in Fiji and to compare the result with some of the side effects provided by other studies. The questionnaire also asked how much kava was consumed and the reasons. Since kava use is very much part of our everyday culture and existence, convincing people to change their behavior and kava consumption is a major tasks. I hope that this study would emphasize the need at a national level to educate people on the harmful effects of kava and the need for the health ministry to view very heavy kava intake as contributing to morbidity in Fiji.

  5. Adverse effects of marijuana use.

    PubMed

    Feeney, Kathleen E; Kampman, Kyle M

    2016-05-01

    Marijuana has consistently been reported as the most commonly used illicit substance in the United States each year. Currently, the legalization of marijuana is up for debate across the nation. While marijuana use is prevalent among the adolescent population, research has shown that there can be devastating effects on health and well-being. A review of the literature shows that marijuana use can have a negative impact on physical health, psychological well-being, and multiple psychosocial outcomes. Adolescents who used marijuana more frequently and began using marijuana at an earlier age experienced worse outcomes and long-lasting effects.

  6. Potential adverse effects of phytoestrogens.

    PubMed

    Whitten, P L; Lewis, C; Russell, E; Naftolin, F

    1995-03-01

    Evaluation of the potential benefits and risks offered by naturally occurring plant estrogens requires investigation of their potency and sites of action when consumed at natural dietary concentrations. Our investigations have examined the effects of a range of natural dietary concentrations of the most potent plant isoflavonoid, coumestrol, using a rat model and a variety of estrogen-dependent tissues and endpoints. Treatments of immature females demonstrated agonistic action in the reproductive tract, brain, and pituitary at natural dietary concentrations. Experiments designed to test for estrogen antagonism demonstrated that coumestrol did not conform to the picture of a classic antiestrogen. However, coumestrol did suppress estrous cycles in adult females. Developmental actions were examined by neonatal exposure of pups through milk of rat dams fed a coumestrol, control, or commercial soy-based diet during the critical period of the first 10 postnatal days or throughout the 21 days of lactation. The 10-day treatment did not significantly alter adult estrous cyclicity, but the 21-day treatment produced in a persistent estrus state in coumestrol-treated females by 132 days of age. In contrast, the 10-day coumestrol treatments produced significant deficits in the sexual behavior of male offspring. These findings illustrate the broad range of actions of these natural estrogens and the variability in potency across endpoints. This variability argues for the importance of fully characterizing each phytoestrogen in terms of its sites of action, balance of agonistic and antagonistic properties, natural potency, and short-term and long-term effects.

  7. Perspective on Lithotripsy Adverse Effects

    NASA Astrophysics Data System (ADS)

    Knoll, Thomas; Wendt-Nordahl, Gunnar

    2008-09-01

    Shock wave lithotripsy (SWL) is an effective and without any doubt the least invasive procedure to treat upper urinary tract calculi. Acute complications are rarely reported and do not require specific treatment in most cases. However, one should be aware that energy levels sufficient for stone breakage are capable of damaging tissue as well, and significant hematoma—not only in the kidney but as well in surrounding organs—has been observed. Furthermore, only little is known about the long-term effects of SWL. Some authors have reported an increased incidence of hypertension and possibly also diabetes mellitus. Such chronic diseases—if indeed related to prior SWL—may be a late result of acute SWL-related trauma but the discussion on the underlying pathogenesis is controversial. Many factors have to be considered, such as the natural history of recurrent stone formers, technical principles of SWL, and differences in treatment protocols. Promising studies are currently underway to optimize stone breakage while limiting potential collateral damage. With this progress, SWL remains a safe treatment option for most urinary calculi.

  8. Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

    PubMed

    Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

    2014-01-01

    Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

  9. ADMA predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus undergoing coronary angiography

    PubMed Central

    Heunisch, Fabian; Chaykovska, Lyubov; von Einem, Gina; Alter, Markus; Dschietzig, Thomas; Kretschmer, Axel; Kellner, Karl-Heinz; Hocher, Berthold

    2017-01-01

    Abstract Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide (NO)-synthase and a biomarker of endothelial dysfunction (ED). ED plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of our study was to evaluate serum ADMA concentration as a biomarker of an acute renal damage during the follow-up of 90 days after contrast medium (CM) application. Blood samples were obtained from 330 consecutive patients with diabetes mellitus or mild renal impairment immediately before, 24 and 48 hours after the CM application for coronary angiography. The patients were followed for 90 days. The composite endpoints were major adverse renal events (MARE) defined as occurrence of death, initiation of dialysis, or a doubling of serum creatinine concentration. Overall, ADMA concentration in plasma increased after CM application, although, there was no differences between ADMA levels in patients with and without CIN. ADMA concentration 24 hours after the CM application was predictive for dialysis with a specificity of 0.889 and sensitivity of 0.653 at values higher than 0.71 μmol/L (area under the curve: 0.854, 95% confidential interval: 0.767–0.941, P < 0.001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. 24 hours after the CM application, ADMA concentration in plasma was predictive for MARE with a specificity of 0.833 and sensitivity of 0.636 at a value of more than 0.70 μmol/L (area under the curve: 0.750, 95% confidence interval: 0.602–0.897, P = 0.004). Multivariate logistic regression analysis confirmed that ADMA and anemia were significant predictors of MARE. Further analysis revealed that increased ADMA concentration in plasma was highly significant predictor of MARE in patients with CIN. Moreover, patients with CIN and MARE had the highest plasma ADMA levels 24 hours after CM exposure in our study

  10. ADMA predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus undergoing coronary angiography.

    PubMed

    Heunisch, Fabian; Chaykovska, Lyubov; von Einem, Gina; Alter, Markus; Dschietzig, Thomas; Kretschmer, Axel; Kellner, Karl-Heinz; Hocher, Berthold

    2017-02-01

    Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide (NO)-synthase and a biomarker of endothelial dysfunction (ED). ED plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of our study was to evaluate serum ADMA concentration as a biomarker of an acute renal damage during the follow-up of 90 days after contrast medium (CM) application.Blood samples were obtained from 330 consecutive patients with diabetes mellitus or mild renal impairment immediately before, 24 and 48 hours after the CM application for coronary angiography. The patients were followed for 90 days. The composite endpoints were major adverse renal events (MARE) defined as occurrence of death, initiation of dialysis, or a doubling of serum creatinine concentration.Overall, ADMA concentration in plasma increased after CM application, although, there was no differences between ADMA levels in patients with and without CIN. ADMA concentration 24 hours after the CM application was predictive for dialysis with a specificity of 0.889 and sensitivity of 0.653 at values higher than 0.71 μmol/L (area under the curve: 0.854, 95% confidential interval: 0.767-0.941, P < 0.001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. 24 hours after the CM application, ADMA concentration in plasma was predictive for MARE with a specificity of 0.833 and sensitivity of 0.636 at a value of more than 0.70 μmol/L (area under the curve: 0.750, 95% confidence interval: 0.602-0.897, P = 0.004). Multivariate logistic regression analysis confirmed that ADMA and anemia were significant predictors of MARE. Further analysis revealed that increased ADMA concentration in plasma was highly significant predictor of MARE in patients with CIN. Moreover, patients with CIN and MARE had the highest plasma ADMA levels 24 hours after CM exposure in our study cohort. The impact

  11. [Laser trabeculoplasty: therapeutic options and adverse effects].

    PubMed

    Wacker, T; Eckert, S

    2010-01-01

    Laser trabeculoplasty is a simple method for treating glaucoma and ocular hypertension and has few adverse effects. There are different laser systems for reducing the intraocular pressure of patients with glaucoma and ocular hypertension. Complications include transient intraocular pressure elevation, iritis, and anterior synechiae.

  12. Effects of Renal Denervation on Renal Artery Function in Humans: Preliminary Study

    PubMed Central

    Doltra, Adelina; Hartmann, Arthur; Stawowy, Philipp; Goubergrits, Leonid; Kuehne, Titus; Wellnhofer, Ernst; Gebker, Rolf; Schneeweis, Christopher; Schnackenburg, Bernhard; Esler, Murray; Fleck, Eckart; Kelle, Sebastian

    2016-01-01

    Aim To study the effects of RD on renal artery wall function non-invasively using magnetic resonance. Methods and Results 32 patients undergoing RD were included. A 3.0 Tesla magnetic resonance of the renal arteries was performed before RD and after 6-month. We quantified the vessel sharpness of both renal arteries using a quantitative analysis tool (Soap-Bubble®). In 17 patients we assessed the maximal and minimal cross-sectional area of both arteries, peak velocity, mean flow, and renal artery distensibility. In a subset of patients wall shear stress was assessed with computational flow dynamics. Neither renal artery sharpness nor renal artery distensibility differed significantly. A significant increase in minimal and maximal areas (by 25.3%, p = 0.008, and 24.6%, p = 0.007, respectively), peak velocity (by 16.9%, p = 0.021), and mean flow (by 22.4%, p = 0.007) was observed after RD. Wall shear stress significantly decreased (by 25%, p = 0.029). These effects were observed in blood pressure responders and non-responders. Conclusions RD is not associated with adverse effects at renal artery level, and leads to an increase in cross-sectional areas, velocity and flow and a decrease in wall shear stress. PMID:27003912

  13. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence.

  14. [Hypertension and palmar plantar erythroderma. Management of adverse events of angiogenetic inhibitors in the treatment of renal cell carcinoma].

    PubMed

    Rolfes, N; Lümmen, G

    2011-11-01

    The introduction of angiogenesis inhibitors has altered the systemic therapy of metastatic renal cell carcinoma. Being a"permanent" medication, the management of side effects has special importance, for adverse events may limit therapy. Hypertension (up to 34% of cases) and palmar plantar erythroderma (6-30% of cases) are common side effects.Blood pressure should be monitored during therapy, and arterial hypertension should be treated with a standard medication. If a hypertensive emergency still occurs, a dose reduction or discontinuation of treatment might be indicated.Prophylaxis may prevent or extenuate palmar plantar erythroderma in many cases, enabling regular chemotherapy as planned. In cases with severe clinical symptoms a reduction or interruption of the dose will be necessary. In most cases local therapy is sufficient.

  15. Metabolic and adverse effects of diuretics.

    PubMed

    Wilcox, C S

    1999-11-01

    Diuretics are among the most frequently prescribed drugs. They enjoy a very high clinical reputation for safety and efficacy. However, more than 3 decades of clinical investigation have disclosed a number of abnormalities in fluid electrolyte handling, metabolism, and other adverse effects that can complicate therapy with diuretic drugs. Some of these complications are a direct extension of the wanted action of the drug. These include extracellular fluid volume depletion, associated orthostatic hypotension, and prerenal azotemia. Others are not a direct action of the diuretic, but can be explained as an intranephronal compensation to the diuretic action. These include hypokalemia, in part to increased potassium secretion secondary to the enhanced tubular fluid flow and aldosterone secretion induced by diuretic administration. Metabolic abnormalities are usually mild. Hyperglycemia and carbohydrate intolerance have been related to diuretic-induced hypokalemia, which inhibits insulin secretion by the beta cells, and reductions in extracellular fluid volume and cardiac output. This is compounded by increases in catecholamines from sympathetic nerve activity which decrease peripheral glucose utilization. A mild increase in serum cholesterol concentration is seen frequently during initiation of diuretic therapy, but during steady state therapy after 6 to 12 months, values usually return to baseline. Knowledge of the more common adverse effects induced by diuretics helps the physician in predicting patients at risk and taking effective steps to anticipate or treat adverse responses.

  16. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors.

  17. Environmental Perchlorate Exposure: Potential Adverse Thyroid Effects

    PubMed Central

    Leung, Angela M.; Pearce, Elizabeth N.; Braverman, Lewis E.

    2014-01-01

    Purpose of review This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Recent findings Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant IQ in groups who would be particularly susceptible to perchlorate effects. An update regarding the recent proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. Summary The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants. PMID:25106002

  18. Effects of radiofrequency ablation on individual renal function: assessment by technetium-99m mercaptoacetyltriglycine renal scintigraphy.

    PubMed

    Mukai, Takashi; Sato, Shuhei; Iguchi, Toshihiro; Mimura, Hidefumi; Yasui, Kotaro; Gobara, Hideo; Saika, Takashi; Nasu, Yasutomo; Kumon, Hiromi; Kanazawa, Susumu

    2006-04-01

    We quantitatively evaluated total and individual renal function by technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) renal scintigraphy before and after radiofrequency ablation (RFA) of renal tumors. Eleven patients who underwent Tc-99m MAG3 renal scintigraphy 1 week before and after RFA were evaluated (7 men and 4 women; age range: 23-83 years; mean age: 60.6 years). Five patients had solitary kidneys, and five had normally or minimally functioning contralateral kidneys. One patient had a renal cell carcinoma in the contralateral kidney. One patient with a solitary kidney underwent RFA a second time for a residual tumor. In patients with a solitary kidney, MAG3 clearance decreased after 5 of 6 RFAs, and in patients with a normally functioning contralateral kidney, MAG3 clearance decreased after 4 of 5 RFAs, but no significant differences were observed between before and after treatments. In addition to the total MAG3 clearance, the split MAG3 clearance was evaluated in patients with a normally functioning contralateral kidney. MAG3 clearance decreased in 4 of 5 treated kidneys, while it adversely increased in the contralateral kidneys after 4 of 5 RFAs. No significant differences, however, were observed between before and after treatments. The results of our study revealed no significant differences in sCr, BUN, CCr, or MAG3 clearance between pre- and post-RFA values. These results support data regarding the functional impact and safety of renal RFA in published reports. We evaluated total and individual renal function quantitatively using Tc-99m MAG3 renal scintigraphy before and after treatment. This scintigraphy was very useful in assessing the effects of RFA on renal function.

  19. Adverse effects of new antiepileptic drugs.

    PubMed

    Onat, Filiz; Ozkara, Cigdem

    2004-04-01

    Starting with phenobarbital in the 1900s, it took almost 70-80 years to introduce old-generation agents for the treatment of epilepsy. Then, in eleven years, nine more new antiepileptic drugs were added to the armamentarium. These drugs produce a nearly 40-50% decrease in seizure incidence in refractory patients, but few patients have been able to achieve complete freedom from seizures. So the search for more effective drugs with minimal adverse effect profiles will continue. Although the new antiepileptic drugs do not demonstrate a superior efficacy compared to the older ones, they do offer some advantages in terms of tolerability, fewer drug interactions and simpler pharmacokinetics. However, our knowledge concerning their safety profiles can not yet be considered adequate due to the relatively short time these drugs have been on the market and to the limited number of patients exposed to them. The fact that the serious side effects of felbamate and vigabatrine appeared late after marketing should be taken as an important lesson because it implies the potential for unknown side effects at any time during treatment. Antiepileptic drug treatment should begin with diagnosis of the seizure and epileptic syndrome, followed by selection of the drug most appropriate for treatment of the individual patient, and continued with monitoring of not only the seizures but the adverse effect profile as well.

  20. Immunomodulatory drugs: Oral and systemic adverse effects

    PubMed Central

    Mattila, Riikka; Gomez-Font, Rafael; Meurman, Jukka H.

    2014-01-01

    Objectives: The main objectives are to present the different adverses effects of the immunomodulatory drugs that can impair the quality of life of the immunosupressed patients and study the impact of immunomodualtion on oral diseases. Immunomodulatory drugs have changed the treatment protocols of many diseases where immune functions play a central role, such as rheumatic diseases. Their effect on oral health has not been systematically investigated, however. Study Design: We review current data on the new immunomodulatory drugs from the oral health perspective based on open literature search of the topic. Results: These target specific drugs appear to have less drug interactions than earlier immunomodulating medicines but have nevertheless potential side effects such as activating latent infections. There are some data showing that the new immunomodulatory drugs may also have a role in the treatment of certain oral diseases such as lichen planus or ameliorating symptoms in Sjögren´s syndrome, but the results have not been overly promising. Conclusions: In general, data are sparse of the effect of these new drugs vs. oral diseases and there are no properly powered randomized controlled trials published on this topic. Key words:Immunomodulatory drugs, oral diseases, adverse effects, therapeutic action. PMID:23986016

  1. Agomelatine: a review of adverse effects.

    PubMed

    2013-03-01

    More pharmacovigilance data on agomelatine became available in 2012. The main sources of information were surveillance data from the French national monitoring system, EU periodic safety update reports (PSURs), and the European pharmacovigilance database. The principal adverse effects of agomelatine consist of hepatic, pancreatic, neuropsychiatric, muscular and cutaneous disorders. The harms associated with agomelatine, which has no proven efficacy in depression, clearly outweigh the benefits. Until regulatory agencies decide to withdraw agomelatine from the market, it is up to healthcare professionals to protect patients from this unnecessarily dangerous drug.

  2. [Adverse drug effects in the community pharmacy].

    PubMed

    Arnet, Isabelle; Seidling, Hanna M; Hersberger, Kurt E

    2015-12-01

    Community pharmacists represent an important pillar for the identification and the reporting of adverse drug effects (ADE}. Thanks to their broad view on the pharmacotherapy, over-the-counter medication included, they contribute greatly to the improvement of drug safety. In principle, the community pharmacy will face three groups of ADE which require specific attention. This article deals with these specific ADE groups and presents some illustrative examples from daily practice. Furthermore, we suggest some solutions to identify potential relevant interactions - including herbal-drug interactions - and give tips for daily practice, along with some often overseen cutaneous ADE.

  3. Adverse Effects of Psychotropic Medications: A Call to Action.

    PubMed

    Mago, Rajnish

    2016-09-01

    Adverse effects are common, bothersome, and a leading cause of discontinuation of treatment. The methodology for evaluating adverse effects of medications has been greatly neglected, however, especially in comparison to the methodology for assessment of efficacy of medications. Existing methods for assessment and reporting of adverse effects have important limitations leading to lack of much-needed data related to adverse effects. Lastly, there is little systematic research into management of most adverse effects. A series of recommendations are made in this article about how to improve identification, assessment, reporting, and management of adverse effects.

  4. Adverse effects of differential parental attention1

    PubMed Central

    Sajwaj, Thomas E.; Pinkston, Susan; Cordua, Glenn; Jackson, Carolyn; Herbert, Emily W.; Pinkston, Elsie M.; Hayden, M. Loeman

    1973-01-01

    In two independent parent training projects (Kansas and Mississippi), mothers of deviant young children were observed to follow almost all child behaviors with attention. The mothers were then trained to use differential attention procedures to increase their child's appropriate behaviors and to decrease deviant behaviors. Contrary to expectations, the differential attention procedure produced substantial increases in deviant behavior for four of the children. This adverse effect was maintained over many sessions and was replicated in single organism, reversal designs. A fifth child showed no change. A sixth child showed some improvement. However, this effect was not recovered in a second application of differential attention, and the child became worse. The results underline the importance of subject generality in applied behavior analysis and strongly suggest that service programs using operant techniques must carefully evaluate their effects on behavior. PMID:16795386

  5. Effects of adenosine infusion into renal interstitium on renal hemodynamics

    SciTech Connect

    Pawlowska, D.; Granger, J.P.; Knox, F.G.

    1987-04-01

    This study was designed to investigate the hemodynamic effects of exogenous adenosine in the interstitium of the rat kidney. Adenosine or its analogues were infused into the renal interstitium by means of chronically implanted capsules. In fusion of adenosine decreased glomerular filtration rate (GFR) from 0.81 +/- 0.06 to 0.37 +/- 0.06 ml/min while having no effect on renal blood flow (RBF). The metabolically stable analogue, 2-chloradenosine (2-ClAdo), decreased GFR from 0.73 +/- 0.07 to 021 +/- 0.06 ml/min. Interstitial infusion of theophylline, an adenosine receptor antagonist, completely abolished the effects of adenosine and 2-ClAdo on GFR. The distribution of adenosine, when infused into the renal interstitium, was determined using radiolabeled 5'-(N-ethyl)-carboxamidoadenosine (NECA), a metabolically stable adenosine agonist. After continuous infusion, (/sup 3/H)NECA was distributed throughout the kidney. The effects of NECA to reduce GFR were similar to those of adenosine and 2-ClAdo. They conclude that increased levels of adenosine in the renal interstitium markedly decrease GFR without affecting RBF in steady-state conditions. The marked effects of adenosine agonists during their infusion into the renal interstitium and the complete blockade of these effects by theophylline suggest an extracellular action of adenosine.

  6. Dectin-1 predicts adverse postoperative prognosis of patients with clear cell renal cell carcinoma

    PubMed Central

    Xia, Yu; Liu, Li; Bai, Qi; Wang, Jiajun; Xi, Wei; Qu, Yang; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

    2016-01-01

    Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases. Moreover, Kaplan-Meier method was conducted and high expression of tumoral dectin-1 was associated with shorter patient recurrence free survival (RFS) and overall survival (OS) (P < 0.001 for both). In multivariate analyses, tumoral dectin-1 expression was also confirmed as an independent prognostic factor for patients’ survival together with other clinical parameters (P < 0.001 for RFS and OS). After incorporating these characteristics including tumoral dectin-1 expression, two nomograms were constructed to predict ccRCC patients’ RFS and OS (c-index 0.796 and 0.812, respectively) and performed better than existed integrated models (P < 0.001 for all models comparisons). In conclusion, high tumoral dectin-1 expression was an independent predictor of adverse clinical outcome in ccRCC patients. This molecule and established nomograms might help clinicians in future decision making and therapeutic developments. PMID:27600310

  7. The NAS Perchlorate Review: Adverse Effects?

    SciTech Connect

    Johnston, Richard B.; Corley, Richard; Cowan, Linda; Utiger, Robert D.

    2005-11-01

    To the editor: Drs. Ginsberg and Rice argue that the reference dose for perchlorate of 0.0007 mg/kg per day recommended by the National Academies’ Committee to Assess the Health Implications of Perchlorate Ingestion is not adequately protective. As members of the committee, we disagree. Ginsberg and Rice base their conclusion on three points. The first involves the designation of the point of departure as a NOEL (no-observed-effect level) versus a LOAEL (lowest-observed-adverse- effect level). The committee chose as its point of departure a dose of perchlorate (0.007 mg/kg per day) that when given for 14 days to 7 normal subjects did not cause a significant decrease in the group mean thyroid iodide uptake (Greer et al. 2002). Accordingly, the committee considered it a NOEL. Ginsberg and Rice focus on the fact that only 7 subjects were given that dose, and they 1seem to say that attention should be paid only to the results in those subjects in whom there was a 1fall in thyroid iodide uptake, and that the results in those in whom there was no fall or an increase should be ignored. They consider the dose to be a LOAEL because of the fall in uptake in those few subjects. It is important to note that a statistically significant decrease of, for example, 5% or even 10%, would not be biologically important and, more important, would not be sustained. For example, in another study (Braverman et al. 2004), administration of 0.04 mg/kg per day to normal subjects for 6 months had no effect on thyroid iodide uptake when measured at 3 and 6 months, and no effect on serum thyroid hormone or thyrotropin concentrations measured monthly (inspection of Figure 5A in the paper by Greer et al. suggests that this dose would inhibit thyroid iodide uptake by about 25% if measured at 2 weeks). The second issue involves database uncertainty. In clinical studies, perchlorate has been administered prospectively to 68 normal subjects for 2 weeks to 6 months. In one study (Brabant et al. 1992

  8. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a) Apply criteria of adverse effect. In consultation with the SHPO/THPO and any Indian tribe or Native...

  9. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  10. Combined ureterorenoscopy for ureteral and renal calculi is not associated with adverse outcomes

    PubMed Central

    Turan, Mirac; Ozkanli, Oguz; Avci, Egemen; Basar, Mehmet Murad; Acar, Oguz; Balbay, Mevlana Derya

    2015-01-01

    Introduction We intended to evaluate the feasibility and effectiveness of the simultaneous rigid and flexible ureteroscopic treatment of symptomatic ureteral and ipsilateral small simultaneous calyceal stones. Outcomes of combined therapy were compared with monotherapy alone. Material and methods In this retrospective study, group 1 consisted of 45 patients with middle or lower ureteral and ipsilateral small simultaneous calyceal stones treated by combined therapy. Group 2 included 45 patients with middle or lower ureteral stones only and treated by monotherapy. Stone characteristics, operative time, hospital stay, stone free rates, and complications were compared between groups 1 and 2. Stone free status was defined as no fragments and/or the presence of asymptomatic fragments smaller than 4 mm. Results Mean BMI were 29.3 ±0.9 kg/m2 and 27.6 ±0.6 kg/m2 in groups 1 and 2, respectively. Mean ureteral stone size (7.6 ±0.4 mm vs. 8.0 ±0.4 mm, p = 0.261) and ureteral stone burden (56.0 ±5.5 mm2 vs. 54.8 ±6.1 mm2, p = 0.487) were similar between groups. Mean renal stone size and renal stone burden for group 1 were 7.1 ±0.8 mm and 83.7 ±11.3 mm2. The mean operative time was significantly longer (for a mean of 32.5±1.2 minutes) for group 1 (p = 0.001). Ureteral stents were left in 38 (84.4%) and 19 (42.2%) patients in group 1 and group 2 (p = 0.001). Hospital stay and complication rates were similar between groups. SFRs were 100% for ureteral stones in both groups and 88.9% for renal stones within group 1. Conclusions Simultaneous ureteroscopic treatment of the ureteral and ipsilateral small calyceal stones prolongs operative time and increases use of ureteral stent without leaving any residual renal stones. PMID:26251739

  11. [Management of adverse effects with antituberculosis chemotherapy].

    PubMed

    Tsuyuguchi, Kazunari; Wada, Masako

    2011-02-01

    Tuberculosis has now become a curable disease with chemotherapy. So it is natural that the present issues in tuberculosis management are focused on how to complete standard chemotherapy. In this context, management of adverse effects constitutes an essential part of antituberculosis chemotherapy, as well as directly observed therapy. In this symposium, discussions were held about three major subjects on this issue. First, hepatotoxicity develops frequently and has sometimes fatal outcome, which makes it the most problematic adverse effect. "Management of hepatotoxicity during antituberculosis chemotherapy" was published by the Japanese Society for Tuberculosis (JST) in 2006. Dr. Shinsho Yoshiba evaluated this recommendation and pointed out that the criteria for discontinuation of drug based on AST, ALT and bilirubin levels is too sensitive and the concept of predicting fulminant hepatic failure (FHF) is lacking. He stressed the importance of monitoring serum prothrombin time for predicting FHF. Next, allergic drug reaction such as fever or skin rash often causes distress, although rarely fatal. As isoniazid (INH) and rifampicin (RFP) are key drugs for the cure, readministration of these drugs is often attempted by desensitization therapy. "Recommendation about desensitization therapy of antituberculosis drugs" was also published by JST in 1997. Dr. Yoshihiro Kobashi reported high success rates of 79 percent for INH and 75 percent for RFP according to this recommendation. He also reported correlated factor with the success, such as the longer period from the discontinuation to the desensitization therapy and lower doses of drugs at starting desensitization. Finally, we sometimes experience transient worsening of radiographical findings and general symptoms during antituberculosis chemotherapy. This is presumed to be due to allergic reaction to dead bacilli without requiring discontinuation of the drug. Differential diagnosis includes drug-induced pneumonia requring

  12. Adverse immunologic effects of antithyroid drugs.

    PubMed Central

    Wing, S S; Fantus, I G

    1987-01-01

    Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299

  13. Metabolic effects of renal denervation.

    PubMed

    Thomopoulos, Costas; Spanoudi, Filio; Kyriazis, Ioannis; Anastasopoulos, Ioannis; Ioannidis, Ioannis

    2013-08-01

    In the present review article we address the issue of the potential effect of renal sympathetic denervation (RSD) on metabolic states associated with resistant hypertension. So far, there is an established pathophysiological background denoting that abnormalities in glucose metabolism especially in obese patients and in those with sleep apnea are constantly accompanied by increased sympathetic firing, as assessed by markers of sympathetic activity. Since resistant hypertension is also characterized by enhanced sympathetic activity, it seems logical and biologically plausible, that RSD might favorably influence impaired glucose metabolism, sleep disorders and increased body adiposity beyond BP lowering. Despite the limited evidence from clinical trials, there are promising data suggesting that RSD indeed ameliorates glucose metabolism-related measures in resistant hypertension. Well-designed randomized trials recruiting a larger number of patients with hypertension, and focused on metabolic parameters, may refine the role of RSD as a potential intervention to treat dysmetabolic states associated with hypertension.

  14. Stimulant Treatment over Five Years: Adherence, Effectiveness, and Adverse Effects.

    ERIC Educational Resources Information Center

    Charach, Alice; Ickowicz, Abel; Schachar, Russell

    2004-01-01

    Objective: To evaluate the impact of adherence and medication status on effectiveness and adverse effects of stimulant use in children with attention-deficit/hyperactivity disorder (ADHD) over 5 years. Method: Seventy-nine of 91 participants in a 12-month randomized controlled trial of methylphenidate and parent groups enrolled in a follow-up…

  15. Clinicians' recognition of the metabolic adverse effects of antipsychotic medications.

    PubMed

    Buckley, Peter F; Miller, Del D; Singer, Beth; Arena, John; Stirewalt, Edna M

    2005-11-15

    There is a growing concern regarding the propensity of second generation antipsychotics (SGAs) to induce weight gain and metabolic adverse effects. Recent consensus guidelines have recommended assessment and monitoring procedures to appropriately detect and manage these adverse effects. This study addresses the appreciation and readiness of clinicians to implement management guidelines for these adverse effects. Respondents indicated awareness of the risks of treatment with SGAs. The extent of monitoring for metabolic adverse effects was low and inconsistent across measures and in frequency of evaluation. Ongoing efforts are needed to support and encourage change in clinician practice.

  16. The adverse health effects of chronic cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2014-01-01

    This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment.

  17. The predictive value of arterial stiffness on major adverse cardiovascular events in individuals with mildly impaired renal function

    PubMed Central

    Han, Jie; Wang, Xiaona; Ye, Ping; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei

    2016-01-01

    Objectives Despite growing evidence that arterial stiffness has important predictive value for cardiovascular disease in patients with advanced stages of chronic kidney disease, the predictive significance of arterial stiffness in individuals with mildly impaired renal function has not been established. The aim of this study was to evaluate the predictive value of arterial stiffness on cardiovascular disease in this specific population. Materials and methods We analyzed measurements of arterial stiffness (carotid–femoral pulse-wave velocity [cf-PWV]) and the incidence of major adverse cardiovascular events (MACEs) in 1,499 subjects from a 4.8-year longitudinal study. Results A multivariate Cox proportional-hazard regression analysis showed that in individuals with normal renal function (estimated glomerular filtration rate [eGFR] ≥90 mL/min/1.73 m2), the baseline cf-PWV was not associated with occurrence of MACEs (hazard ratio 1.398, 95% confidence interval 0.748–2.613; P=0.293). In individuals with mildly impaired renal function (eGFR <90 mL/min/1.73 m2), a higher baseline cf-PWV level was associated with a higher risk of MACEs (hazard ratio 2.334, 95% confidence interval 1.082–5.036; P=0.031). Conclusion Arterial stiffness is a moderate and independent predictive factor for MACEs in individuals with mildly impaired renal function (eGFR <90 mL/min/1.73 m2). PMID:27621605

  18. 36 CFR 800.7 - Failure to resolve adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... effects. 800.7 Section 800.7 Parks, Forests, and Public Property ADVISORY COUNCIL ON HISTORIC PRESERVATION PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.7 Failure to resolve adverse effects. (a) Termination of consultation. After consulting to resolve adverse effects pursuant to § 800.6(b)(2), the...

  19. [Pharmacology of misoprostol (pharmacokinetic data, adverse effects and teratogenic effects)].

    PubMed

    Aubert, J; Bejan-Angoulvant, T; Jonville-Bera, A-P

    2014-02-01

    Misoprostol is a synthetic analogue of prostaglandin E1. It is used in gynaecology because of its properties of myometrium smooth muscle cells contraction and its effects on the cervix. Misoprostol oral bioavailability is low and several authors have assessed whether the administration by other routes increased its pharmacodynamic effects. This paper summarizes the pharmacokinetic studies after other routes of administration: vaginal, sublingual, buccal or rectal. It also provides an update on its adverse effects and teratogenic effects.

  20. Using Literature-Based Discovery to Explain Adverse Drug Effects.

    PubMed

    Hristovski, Dimitar; Kastrin, Andrej; Dinevski, Dejan; Burgun, Anita; Žiberna, Lovro; Rindflesch, Thomas C

    2016-08-01

    We report on our research in using literature-based discovery (LBD) to provide pharmacological and/or pharmacogenomic explanations for reported adverse drug effects. The goal of LBD is to generate novel and potentially useful hypotheses by analyzing the scientific literature and optionally some additional resources. Our assumption is that drugs have effects on some genes or proteins and that these genes or proteins are associated with the observed adverse effects. Therefore, by using LBD we try to find genes or proteins that link the drugs with the reported adverse effects. These genes or proteins can be used to provide insight into the processes causing the adverse effects. Initial results show that our method has the potential to assist in explaining reported adverse drug effects.

  1. Programmatic Considerations to Reduce the Risk of Adverse Renal Stone Events in Spaceflight

    NASA Technical Reports Server (NTRS)

    Antonsen, Erik; Pietrzyk, Robert

    2017-01-01

    Introduction: Microgravity exposure may alter the likelihood that astronauts will experience renal stones. The potential risk includes both acute and chronic health issues, with the potential for significant impact on mission objectives. Methods: To understand the role of the NASA's Human Research Program (HRP) research agenda in both preventing and addressing renal stones in spaceflight, current astronaut epidemiologic data and a summary of programmatic considerations are reviewed. Results: Although there has never been a symptomatic renal stone event in a U.S. crewmember during spaceflight, urine chemistry has been altered - likely due to induced changes in renal physiology as a result of exposure to microgravity. This may predispose astronauts to stone formation, leading the HRP to conduct and sponsor research to: 1) understand the risk of stone formation in space; 2) prevent stones from forming; and 3) address stones that may form by providing novel diagnostic and therapeutic approaches. Discussion: The development of a renal stone during spaceflight is a significant medical concern that requires the HRP to minimize this risk by providing the ability to prevent, diagnose, monitor and treat the condition during spaceflight. A discussion of the risk as NASA understands it is followed by an overview of the multiple mitigations currently under study, including novel ultrasound techniques for stone detection and manipulation, and how they may function as part of a larger exploration medical system.

  2. The effects of environmental chemicals on renal function.

    PubMed

    Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

    2015-10-01

    The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease.

  3. The effects of environmental chemicals on renal function

    PubMed Central

    Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

    2015-01-01

    The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease. PMID:26100504

  4. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  5. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  6. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  7. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  8. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  9. Nonhemostatic adverse effects of anticoagulants and antiplatelet agents.

    PubMed

    Walenga, Jeanine M; Thethi, Indermohan; Lewis, Bruce E

    2012-11-01

    The topic of adverse effects of drugs is now receiving due attention in both the lay and medical communities. For drugs of the coagulation disorder class, such as anticoagulants and antiplatelet agents, the obvious adverse effects are bleeding from a dose too high and thrombosis from a dose too low. However, these drugs have other potential adverse effects that are not directly related to blood coagulation, yet cannot be dismissed due to their medical importance. There has been a recent advancement of several new drugs in this category and this number will soon grow as more drugs are reaching the end of their clinical trials. This article will discuss the nonhemostatic adverse effects of anticoagulants and antiplatelet drugs. As the adverse effects of bleeding and thrombosis will be excluded, this article will be in contrast to the typical discussions on the anticoagulant and antiplatelet drug classes.

  10. Adverse health effects of non-medical cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2009-10-17

    For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest-that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.

  11. Renal vascular effects of calcium channel blockers in hypertension.

    PubMed

    Benstein, J A; Dworkin, L D

    1990-12-01

    Recent evidence suggests that calcium channel blockers have specific effects on renal hemodynamics in patients with hypertension and may also slow the progression of chronic renal failure. When these agents are studied in vitro, their predominant effect is to reverse afferent arteriolar vasoconstriction induced by catecholamines or angiotensin II. Because efferent resistance may remain high, glomerular filtration rate rises while renal blood flow remains low. The effects in vivo are less consistent. In human hypertension, calcium channel blockers lower renal resistance and may raise both renal blood flow and glomerular filtration rate. In experimental models of chronic renal disease, calcium channel blockers slow the progression of renal damage; however, variable effects on renal hemodynamics have been found. Other factors implicated in the progression of renal damage, including compensatory renal hypertrophy, platelet aggregation, and calcium deposition, may also be favorably influenced by these agents. Recent studies suggest that calcium channel blockers may have similar protective effects in patients with hypertension and chronic renal disease.

  12. Rare and very rare adverse effects of clozapine

    PubMed Central

    De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

    2015-01-01

    Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

  13. Adverse effects of public health interventions: a conceptual framework.

    PubMed

    Lorenc, Theo; Oliver, Kathryn

    2014-03-01

    Public health interventions may have a range of adverse effects. However, there is limited guidance as to how evaluations should address the possibility of adverse effects. This discussion paper briefly presents a framework for thinking about the potential harms of public health interventions, focusing on the following categories: direct harms; psychological harms; equity harms; group and social harms; and opportunity harms. We conclude that the possibility of adverse effects needs to be taken into account by those implementing and evaluating interventions, and requires a broad perspective on the potential impacts of public health strategies.

  14. Adverse effects of shock waves and strategies for improved treatment in shock wave lithotripsy

    NASA Astrophysics Data System (ADS)

    McAteer, James A.; Evan, Andrew P.; Connors, Bret A.; Williams, James C.; Willis, Lynn R.

    2005-04-01

    Lithotripter SWs rupture blood vessels in the kidney. This acute trauma, accompanied by a fall in renal function, can lead to significant long-term effects such as profound scarring of the kidney cortex and renal papillaea permanent loss of functional renal mass. SWL has been linked to new-onset hypertension in some patients, and recent studies suggest that multiple lithotripsies can actually alter a patient's stone disease leading to formation of stones (brushite) that are harder to break. Cavitation and shear appear to play a role in stone breakage and tissue damage. Progress in understanding these mechanisms, and the renal response to SWs, has led to practical strategies to improve treatment. Slowing the SW-rate, or initiating treatment at low kV/power both improve stone breakage and reduce the number of potentially tissue-damaging SWs needed to achieve comminution. The observation that SWs cause transient vasoconstriction in the kidney has led to studies in pigs showing that a pre-conditioning dose of low-energy SWs significantly reduces trauma from subsequent high-energy SWs. Thus, SWs can induce adverse effects in the kidney, but what we have learned about the mechanisms of SW action suggests strategies that could make lithotripsy safer and more effective. [Work supported by NIH-DK43881, DK55674.

  15. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate for... sheepherding) in the following States, and for Florida sugarcane work, shall be computed by adjusting the...

  16. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate for... sheepherding) in the following States, and for Florida sugarcane work, shall be computed by adjusting the...

  17. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate for... sheepherding) in the following States, and for Florida sugarcane work, shall be computed by adjusting the...

  18. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate for... sheepherding) in the following States, and for Florida sugarcane work, shall be computed by adjusting the...

  19. Plasma neutrophil gelatinase-associated lipocalin as a potential predictor of adverse renal outcomes in immunoglobulin A nephropathy

    PubMed Central

    Park, Ga-Young; Yu, Chung-Hoon; Kim, Jun-Seop; Kang, Yun-Jeong; Kwon, Owen; Choi, Ji-Young; Cho, Jang-Hee; Kim, Chan-Duck; Kim, Yong-Lim

    2015-01-01

    Background/Aims Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). Methods In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. Results The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. Conclusions pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value. PMID:25995665

  20. Environmental lead and renal effects in children.

    PubMed

    Verberk, M M; Willems, T E; Verplanke, A J; De Wolff, F A

    1996-01-01

    The effect of lead on five renal-effect parameters was studied in 151 children (i.e., 3-6-y-olds) who resided at different distances from a lead smelter in Baia Mare, Romania. A relationship was found between concentration of lead in blood (mean +/- standard deviation: 342 +/- 224 microgram/l) and the activity of N-acetyl-beta-D-glucosaminidase in urine, as demonstrated by a 14% increase of N-acetyl-beta-D-glucosaminidase per 100 micrograms/l blood lead that was indicative of renal tubular damage. No relationship was found between blood lead level and the renal-effect parameters albumin, alpha-1-microglobulin, retinol binding protein, or alanine aminopeptidase in urine. Cadmium in blood was not elevated. It is well known that N-acetyl-beta-D-glucosaminidase is a sensitive parameter for renal effects, resulting from lead exposure in adults and from diabetes and nephrotoxic medicines in children. This study is the first to demonstrate an effect of environmental lead exposure on renal integrity in children.

  1. Adverse effects of herbal medicines: an overview of systematic reviews.

    PubMed

    Posadzki, Paul; Watson, Leala K; Ernst, Edzard

    2013-02-01

    This overview of systematic reviews (SRs) aims to evaluate critically the evidence regarding the adverse effects of herbal medicines (HMs). Five electronic databases were searched to identify all relevant SRs, with 50 SRs of 50 different HMs meeting our inclusion criteria. Most had only minor weaknesses in methods. Serious adverse effects were noted only for four HMs: Herbae pulvis standardisatus, Larrea tridentate, Piper methysticum and Cassia senna. The most severe adverse effects were liver or kidney damage, colon perforation, carcinoma, coma and death. Moderately severe adverse effects were noted for 15 HMs: Pelargonium sidoides, Perna canaliculus, Aloe vera, Mentha piperita, Medicago sativa, Cimicifuga racemosa, Caulophyllum thalictroides, Serenoa repens, Taraxacum officinale, Camellia sinensis, Commifora mukul, Hoodia gordonii, Viscum album, Trifolium pratense and Stevia rebaudiana. Minor adverse effects were noted for 31 HMs: Thymus vulgaris, Lavandula angustifolia Miller, Boswellia serrata, Calendula officinalis, Harpagophytum procumbens, Panax ginseng, Vitex agnus-castus, Crataegus spp., Cinnamomum spp., Petasites hybridus, Agave americana, Hypericum perforatum, Echinacea spp., Silybum marianum, Capsicum spp., Genus phyllanthus, Ginkgo biloba, Valeriana officinalis, Hippocastanaceae, Melissa officinalis, Trigonella foenum-graecum, Lagerstroemia speciosa, Cnicus benedictus, Salvia hispanica, Vaccinium myrtillus, Mentha spicata, Rosmarinus officinalis, Crocus sativus, Gymnema sylvestre, Morinda citrifolia and Curcuma longa. Most of the HMs evaluated in SRs were associated with only moderately severe or minor adverse effects.

  2. Adverse Health Effects of Nighttime Lighting

    NASA Astrophysics Data System (ADS)

    Motta, M.

    2012-06-01

    The effects of poor lighting and glare on public safety are well-known, as are the harmful environmental effects on various species and the environment in general. What is less well-known is the potential harmful medical effects of excessive poor nighttime lighting. A significant body of research has been developed over the last few years regarding this problem. One of the most significant effects is the startling increased risk for breast cancer by excessive exposure to nighttime lighting. The mechanism is felt to be by disruption of the circadian rhythm and suppression of melatonin production from the pineal gland. Melatonin has an anticancer effect that is lost when its production is disrupted. I am in the process of developing a monograph that will summarize this important body of research, to be presented and endorsed by the American Medical Association, and its Council of Science and Public health. This paper is a brief overall summary of this little known potential harmful effect of poor and excessive nighttime lighting.

  3. Adverse effects of stress on microbiota

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The complex communities of microorganisms that colonize the gastrointestinal tract impact the health status of an animal. The health of an animal as well as production traits are also affected by exposure to stress. The aim of present study was to evaluate the effects of dehorning stress on the gut ...

  4. Potential adverse health effects of wood smoke

    SciTech Connect

    Pierson, W.E.; Koenig, J.Q.; Bardana, E.J. Jr.

    1989-09-01

    The use of wood stoves has increased greatly in the past decade, causing concern in many communities about the health effects of wood smoke. Wood smoke is known to contain such compounds as carbon monoxide, nitrogen oxides, sulfur oxides, aldehydes, polycyclic aromatic hydrocarbons, and fine respirable particulate matter. All of these have been shown to cause deleterious physiologic responses in laboratory studies in humans. Some compounds found in wood smoke--benzo(a)pyrene and formaldehyde--are possible human carcinogens. Fine particulate matter has been associated with decreased pulmonary function in children and with increased chronic lung disease in Nepal, where exposure to very high amounts of wood smoke occurs in residences. Wood smoke fumes, taken from both outdoor and indoor samples, have shown mutagenic activity in short-term bioassay tests. Because of the potential health effects of wood smoke, exposure to this source of air pollution should be minimal.29 references.

  5. The ability of pretransplant test-dose pharmacokinetic profiles to reduce early adverse events after renal transplantation.

    PubMed

    Kahan, B D; Welsh, M; Rutzky, L; Lewis, R; Knight, R; Katz, S; Napoli, K; Grevel, J; Van Buren, C T

    1992-02-01

    Pretransplant test-dose pharmacokinetic profiles were used to determine individual cyclosporine drug bioavailability and clearance rates in renal transplant patients. Assuming a linear relation between dose and area under the concentration curve (AUC), starting i.v. and p.o. CsA doses were computed from the test-dose results. Target values were 400 ng/ml steady-state concentration (Css) during continuous intravenous infusion, and 500 ng/ml average drug concentration (Cavss = AUC/dosing interval) after oral administration, based upon measurements with the specific monoclonal antibody 3H-tracer radioimmunoassay. The outcomes after dose individualization with a 1-(n = 32), 2-(n = 38), or 3-(n = 41) hr i.v. infusion test dose and a p.o. test dose (n = 111) were compared with 228 historical control patients who received a uniform protocol of CsA i.v. at 2.5 mg/kg/day and p.o. at 14 mg/kg/day. The observed Css after i.v. CsA was within 10% of the target concentration in 73% of recipients tested with the 3-hr protocol, a significantly greater fraction than achieved with either the uniform dose (14%), or the 1-(34%) and 2-(25%) hr protocols. Patients in the 3-hr protocol group showed reduced incidences of delayed graft function, early graft loss, and rejection episodes, and a lower mean serum creatinine value, particularly at 7 but also at 30 days posttransplantation. Administration of the predicted oral dose produced a peak concentration of greater than or equal to 700 ng/ml drug absorption in 60% of recipients at 3 days, 90% at 5 days, and 98% at 7 days. The test-dose method less effectively predicted the appropriate oral CsA dose to produce target Cssav and failed to reduce the 90-day rejection incidence. Despite its limitations with the more-complicated p.o. route, the test-dose method successfully predicts i.v. CsA doses, thereby reducing the incidence of early adverse events.

  6. [Statin-induced adverse effects -- facts and genes].

    PubMed

    Harangi, Mariann; Zsíros, Noémi; Juhász, Lilla; Paragh, György

    2013-01-20

    Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients.

  7. Adverse effects of isolation in hospitalised patients: a systematic review.

    PubMed

    Abad, C; Fearday, A; Safdar, N

    2010-10-01

    The use of transmission precautions such as contact isolation in patients known to be colonised or infected with multidrug-resistant organisms is recommended in healthcare institutions. Although essential for infection control, contact isolation has recently been associated with adverse effects in patients. We undertook a systematic review to determine whether contact isolation leads to psychological or physical problems for patients. Studies were included if (1) hospitalised patients were placed under isolation precautions for an underlying medical indication, and (2) any adverse events related to the isolation were evaluated. We found 16 studies that reported data regarding the impact of isolation on patient mental well-being, patient satisfaction, patient safety or time spent by healthcare workers in direct patient care. The majority showed a negative impact on patient mental well-being and behaviour, including higher scores for depression, anxiety and anger among isolated patients. A few studies also found that healthcare workers spent less time with patients in isolation. Patient satisfaction was adversely affected by isolation if patients were kept uninformed of their healthcare. Patient safety was also negatively affected, leading to an eight-fold increase in adverse events related to supportive care failures. We found that contact isolation may negatively impact several dimensions of patient care. Well-validated tools are necessary to investigate these results further. Large studies examining a number of safety indicators to assess the adverse effects of isolation are needed. Patient education may be an important step to mitigate the adverse psychological effects of isolation and is recommended.

  8. Adverse effects of the radioprotector WR2721

    SciTech Connect

    Cairnie, A.B.

    1983-04-01

    S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR2721) has radioprotective properties, but it is also toxic - in man it causes nausea and vomiting. Since radiation also causes nausea and vomiting it is important to know whether WR2721 would increase or decrease the likelihood of nausea and vomiting after radiation. This question was investigated in rats using the phenomenon of aversion to the taste of saccharin, which is readily inducible and is understood to be controlled in rats by the same pathways that control nausea and vomiting in man. The taste aversion was induced by giving 0.2 Gy /sup 60/Co ..gamma.. radiation 30 min after drinking 0.1% saccharin, or WR2721 immediately after the saccharin, or giving both radiation and WR2721. There were appropriate controls. In sham-irradiated rats, WR2721 (40 or 200 mg/kg, but not 8 mg/kg) produced a significant taste aversion. When WR2721 (40 or 200 mg/kg) was given immediately after the saccharin to irradiated rats it increased the taste aversion significantly, but it did not have any effect at 8 mg/kg. It was concluded that at doses which were optimal for radioprotection (approx.200 mg/kg) or lower, WR2721 increased in rats the taste aversion induced by radiation. By inference if conditioned taste aversion is an appropriate paradigm, WR2721 would increase nausea and vomiting in man induced by radiation.

  9. Adverse effects of thyroid hormone preparations and antithyroid drugs.

    PubMed

    Bartalena, L; Bogazzi, F; Martino, E

    1996-07-01

    Thyroid hormone preparations, especially thyroxine, are widely used either at replacement doses to correct hypothyroidism or at suppressive doses to abolish thyrotropin (thyroid-stimulating hormone) secretion in patients with differentiated thyroid carcinoma after total thyroidectomy or with diffuse/ nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is necessary to administer slightly supraphysiological doses of thyroxine. Possible adverse effects of this therapy include cardiovascular changes (shortening of systolic time intervals, increased frequency of atrial premature beats and, possibly, left ventricular hypertrophy) and bone changes (reduced bone density and bone mass), but the risk of these adverse effects can be minimised by carefully monitoring serum free thyroxine and free liothyronine (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely used antithyroid drugs. They are given for long periods of time and cause adverse effects in 3 to 5% of patients. In most cases, adverse effects are minor and transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life-threatening condition can now be effectively treated by granulocyte colony-stimulating factor administration. Other major adverse effects (aplastic anaemia, thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly rare.

  10. [Desired effects and adverse effects of cannabis use].

    PubMed

    Drewe, J

    2003-06-01

    Although the use of cannabis shows no pronounced acute toxicity, acute psychological and psychomotor disturbances are observed occasionally after intake of single doses. Cannabis use can result in relevant impairment of driving ability. The risk is enhanced by concomitant use of alcohol. This augments the effect of cannabis significantly. After chronic use, significantly more psychotic symptoms become manifest, and there is a risk for developing psychological and physical dependence. Young age and pre-existing psychological disturbances increase the risk of these adverse effects. Chronic marijuana smoking is associated with increased toxicity and the risk of cancer of the respiratory tract. There is evidence of disturbance of the immune system and teratogenic effects of chronic cannabis use.

  11. Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

    PubMed Central

    Ajaltouni, Jean

    2015-01-01

    The misuse of nootropics—any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters—may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of our knowledge this has not been previously reported in the formal medical literature. We briefly describe the most common classes of nootropics, including their postulated or proven methods of actions, their desired effects, and their adverse side effects, and provide a brief discussion of the cases. Our objective is to raise awareness among physicians in general and psychiatrists and addiction specialists in particular of the potentially dangerous phenomenon of unsupervised nootropic use among young adults who may be especially vulnerable to nootropics’ negative effects. PMID:27222762

  12. Renal

    MedlinePlus

    ... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant

  13. Misuse of topical corticosteroids: A clinical study of adverse effects

    PubMed Central

    Dey, Vivek Kumar

    2014-01-01

    Background: Misuse of topical corticosteroids is a widespread phenomenon among young people in India, especially women. The practice is associated with significant adverse effects and poor awareness of these effects among the general public. Aim: This study was conducted to examine the misuse and adverse effects of topical corticosteroids among the people in Bastar region in Chhattisgarh state of India. Materials and Methods: Data collected from patients presenting with at least one of the adverse effects of topical corticosteroids as the chief complaint, from November 2010 to October 2011. Results: Out of the 6723 new patients, 379 (5.63%) had presented with misuse and adverse effects of topical corticosteroids, of whom 78.89% were females. More than 65% of the patients were in the age group 10-29 years. The main reason for using the topical corticosteroids was to lighten skin colour and treat melasma and suntan. Acne (37.99%) and telangiectasia (18.99%) were the most common adverse effects noted. Conclusions: Misuse of topical corticosteroids has a huge impact on dermatological practice, leading to a significant proportion of visits to the dermatologist. This hydra-headed problem needs multi-dimensional interventions, involving educational, legal and managerial approaches with cooperation from different sectors of society. PMID:25396124

  14. Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers

    PubMed Central

    Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong

    2016-01-01

    Introduction Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Methods Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60–89 mL/min; N=8), moderate (eCrCl 30–59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Results Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration–time curve by 34%, 54%–65%, and 102%, respectively. Lesinurad plasma Cmax was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Conclusion Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment. PMID:27843295

  15. Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo.

    PubMed

    Reichman, J; Cohen, S; Goldfarb, M; Shina, A; Rosen, S; Brezis, M; Karmeli, F; Heyman, S N

    2001-01-01

    The constitutive cyclooxygenase (COX)-1 enzyme has been considered the physiologically important isoform for prostaglandin synthesis in the normal kidney. It has, therefore, been suggested that selective inhibitors of the 'inducible' isoform (COX-2) may be free from renal adverse effects. We studied the renal effects of the predominantly COX-2 antagonist nabumetone in isolated perfused kidneys. As compared with controls, kidneys removed after in vivo administration of oral nabumetone (15 mg/kg) disclosed altered renal function with reduced glomerular filtration rate, filtration fraction, and urine volume and enhanced hypoxic outer medullary tubular damage. By contrast, renal function and morphology were not affected in vivo by nabumetone or its active metabolite 6-methoxy-2-naphthylacetic acid. The latter agent (10-20 mg/kg i.v.) did not significantly alter renal microcirculation, as opposed to a selective substantial reduction in medullary blood flow noted with the nonselective COX inhibitor indomethacin (5 mg/kg i.v.). In a rat model of acute renal failure, induced by concomitant administration of radiocontrast, nitric oxide synthase, and COX inhibitors, the decline in kidney function and the extent of hypoxic medullary damage with oral nabumetone (80 mg/kg) were comparable to a control group, and significantly less than those induced by indomethacin. In rats subjected to daily oral nabumetone for 3 consecutive weeks, renal function and morphology were preserved as well. Both nabumetone and 6-methoxy-2-naphthylacetic acid reduced renal parenchymal prostaglandin E2 to the same extent as indomethacin. It is concluded that while nabumetone adversely affects renal function and may intensify hypoxic medullary damage ex vivo, rat kidneys are not affected by this agent in vivo, both in acute and chronic studies. COX selectivity may not explain the renal safety of nabumetone.

  16. Adverse effects of orthodontic treatment: A clinical perspective

    PubMed Central

    Talic, Nabeel F.

    2011-01-01

    Orthodontic treatment is associated with a number of adverse effects, such as root resorption, pain, pulpal changes, periodontal disease, and temporomandibular dysfunction (TMD). Orthodontists should be aware of these effects and associated risk factors. Risk factors linked to root resorption include the duration of treatment, length, and shape of the root, trauma history, habits, and genetic predisposition. PMID:24151415

  17. Neurological adverse effects of methylphenidate may be misdiagnosed as meningoencephalitis.

    PubMed

    Snell, Luke Blagdon; Bakshi, Dinkar

    2015-06-16

    We present a case of adverse neurological effects of methylphenidate therapy for attention deficit and hyperactivity disorder (ADHD). A 7-year-old boy presented to the emergency department (ED) having developed ataxic gait, orofacial dyskinesias and choreoathetosis of the limbs. The results of all blood investigations, EEG and CT scan of the head were unremarkable. Subsequently, a detailed history revealed he was being treated for ADHD, being started on methylphenidate in the past 3 months. Discontinuation of methylphenidate led to significant and rapid amelioration of neurological adverse effects.

  18. Registered Nurses' Knowledge about Adverse Effects of Analgesics when Treating Postoperative Pain in Patients with Dementia.

    PubMed

    Rantala, Maija; Hartikainen, Sirpa; Kvist, Tarja; Kankkunen, Päivi

    2015-08-01

    Registered nurses (RNs) play a pivotal role in treating pain and preventing and recognizing the adverse effects (AEs) of analgesics in patients with dementia. The purpose of this study was to determine RNs' knowledge of potentially clinically relevant AEs of analgesics. A descriptive, cross-sectional study design was used. In all, 267 RNs treating orthopedic patients, including patients with dementia, in 7 university hospitals and 10 central hospitals in Finland, completed a questionnaire. Analgesics were defined according to the Anatomic Therapeutic Classification as strong opioids, weak opioids, nonsteroidal anti-inflammatory analgesics (NSAIDs), and paracetamol. Definitions of AEs were based on the literature. Logistic regression analysis was applied to analyze which variables predicted nurses' knowledge. The RNs had a clear understanding of the AEs of paracetamol and strong opioids. However, the AEs of NSAIDs, especially renal and cardiovascular AEs, were less well known. The median percentage of correct answers was 87% when asked about strong opioids, 73% for weak opioids, and 60% for NSAIDs. Younger RNs had better knowledge of opioid-related AEs (odds ratio [OR] per 1-year increase, 0.97; 95% confidence interval [CI], 0.94-1.00) and weak opioids (OR, 0.96; 95% CI, 0.93-0.99). This study provides evidence of a deficiency in RNs' knowledge, especially regarding the adverse renal and cardiovascular effects of NSAIDs. Such lack of knowledge indicates that hospitals may need to update the knowledge of older RNs, especially those who treat vulnerable patients with dementia.

  19. Immune-mediated Adverse Effects of Anti-CTLA-4 Antibody Therapy in Metastatic Melanoma

    PubMed Central

    Quirk, Shannon K.; Shure, Anna K.; Agrawal, Devendra K.

    2015-01-01

    Ipilimumab, an antibody that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular effects, renal effects, neurologic effects, and others. In this article, a critical evaluation of the underlying mechanisms of irAEs associated with anti-CTLA-4 therapy is presented. Additionally, potentially beneficial effects of combinational therapies to alleviate ipilimumab-induced irAEs in malignant melanoma are discussed. Future research is warranted to elucidate the efficacy of such combination therapies as well as specific biomarkers that would help to predict a clinical response to ipilimumab in patients with malignant melanoma. PMID:26118951

  20. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  1. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  2. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  3. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  4. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information §...

  5. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information §...

  6. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information §...

  7. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information §...

  8. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information §...

  9. Skin-lightening cosmetics: frequent, potentially severe adverse effects.

    PubMed

    2011-09-01

    Skin-lightening cosmetics are used by many women and men around the world. The products contain a variety of substances, which are often unknown to the users. Most of these products include topical corticosteroids, hydroquinone and mercury salts. Many other substances may be added. Several surveys and cohort studies, including several thousand individuals, have shown that regular application of skin-lightening cosmetics to large surface areas can have irreversible cutaneous adverse effects, such as patchy hyper- or hypopigmentation, skin atrophy, stretch marks and delayed wound healing, and can also mask or, on the contrary, promote or reactivate skin infections. Cases of skin cancer have been attributed to skin-lightening cosmetics. A Senegalese cohort study of 147 women showed a statistically significant increase in the risk of hypertension and diabetes linked to the use of skin-lightening agents. Other systemic adverse effects attributed to skin-lightening cosmetics include Cushing's syndrome, adrenal insufficiency, nephrotic syndrome, neurological disorders, and ocular disorders. Hypersensitivity reactions, including anaphylaxis, have also been attributed to these products. Many skin-lightening cosmetics contain substances that can harm the unborn child. For example, tretinoin is teratogenic while salicylic acid is feto-toxic. In practice, users are often unaware of the risk of severe adverse effects associated with skin-lightening cosmetics. Users should be informed of these adverse effects and encouraged to stop using these products, especially when skin disorders appear.

  10. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a) Apply... have been identified subsequent to the original evaluation of the property's eligibility for the... qualities of a property of religious and cultural significance to an Indian tribe or Native...

  11. Mixed-effects Poisson regression analysis of adverse event reports

    PubMed Central

    Gibbons, Robert D.; Segawa, Eisuke; Karabatsos, George; Amatya, Anup K.; Bhaumik, Dulal K.; Brown, C. Hendricks; Kapur, Kush; Marcus, Sue M.; Hur, Kwan; Mann, J. John

    2008-01-01

    SUMMARY A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)’s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system. PMID:18404622

  12. Indoor air pollution: Acute adverse health effects and host susceptibility

    SciTech Connect

    Zummo, S.M.; Karol, M.H.

    1996-01-01

    Increased awareness of the poor quality of indoor air compared with outdoor air has resulted in a significant amount of research on the adverse health effects and mechanisms of action of indoor air pollutants. Common indoor air agents are identified, along with resultant adverse health effects, mechanisms of action, and likely susceptible populations. Indoor air pollutants range from biological agents (such as dust mites) to chemical irritants (such as nitrogen dioxide, carbon monoxide, sulfur dioxide, formaldehyde, and isocyanates). These agents may exert their effects through allergic as well as nonallergic mechanisms. While the public does not generally perceive poor indoor air quality as a significant health risk, increasing reports of illness related to indoor air and an expanding base of knowledge on the health effects of indoor air pollution are likely to continue pushing the issue to the forefront.

  13. Effect of wettability on adverse mobility immiscible floods

    SciTech Connect

    Vives, M.T.; Chang, Y.C.; Mohanty, K.K.

    1995-12-31

    Many immiscible displacements in reservoirs occur at adverse mobility. Effect of wettability on these displacements is not well understood and often ignored in reservoir simulation. Recent macroscopic theories of viscous fingering treat adverse immiscible flows similar to miscible flows, the mixing in the fingered region being controlled by a Todd-Longstaff-type functional form. The wettability of the medium is taken into account only through the use of appropriate relative permeabilities. The goal of this paper is to understand the macroscopic bypassing in adverse mobility immiscible floods. Immiscible displacements are conducted in a quarter 5-spot model in both drainage and imbibition modes at similar effective mobility ratios and viscous-to-gravity numbers. The level of bypassing and gravity override is visualized and measured. Tertiary water-alternating-gas (WAG) displacements are also conducted at various WAG ratios and viscosity ratios. Fractional flow analysis and numerical simulation are used to understand these displacements. Experiments show that macroscopic viscous fingering is present in adverse viscosity immiscible displacements where no saturation shock is expected from 1-D fractional flow theory. Bypassing due to both fingering and gravity override is higher in the drainage mode than in the imbibition mode, with other key parameters being the same. Optimum WAG ratio in water-wet rock is a function of oil/solvent viscosity ratio. The macroscopic flow theory needs to include capillarity and viscous fingering to match these experimental findings.

  14. Energy Drink Consumption: Beneficial and Adverse Health Effects

    PubMed Central

    Alsunni, Ahmed Abdulrahman

    2015-01-01

    Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents. PMID:26715927

  15. Adverse Effects of Bisphosphonates: Implications for Osteoporosis Management

    PubMed Central

    Kennel, Kurt A.; Drake, Matthew T.

    2009-01-01

    Bisphosphonates are widely prescribed and highly effective at limiting the bone loss that occurs in many disorders characterized by increased osteoclast-mediated bone resorption, including senile osteoporosis in both men and women, glucocorticoid-associated osteoporosis, and malignancies metastatic to bone. Although they are generally well tolerated, potential adverse effects may limit bisphosphonate use in some patients. Optimal use of bisphosphonates for osteoporosis requires adequate calcium and vitamin D intake before and during therapy. The World Health Organization fracture risk assessment algorithm is currently available to determine absolute fracture risk in patients with low bone mass and is a useful tool for clinicians in identifying patients most likely to benefit from pharmacological intervention to limit fracture risk. This fracture risk estimate may facilitate shared decision making, especially when patients are wary of the rare but serious adverse effects that have recently been described for this class of drugs. PMID:19567717

  16. Energy Drink Consumption: Beneficial and Adverse Health Effects.

    PubMed

    Alsunni, Ahmed Abdulrahman

    2015-10-01

    Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents.

  17. A Fatal Adverse Effect of Barbiturate Coma Therapy: Dyskalemia

    PubMed Central

    Kwon, Hyun Mook; Baek, Jin Wook; Lee, Sang Pyung

    2016-01-01

    The management guideline for traumatic brain injury (TBI) recommends high-dose barbiturate therapy to control increased intracranial pressure refractory to other therapeutic options. High-dose barbiturate therapy, however, may cause many severe side effects; the commonly recognized ones include hypotension, immunosuppression, hepatic dysfunction, renal dysfunction, and prolonged decrease of cortical activity. Meanwhile, dyskalemia remains relatively uncommon. In this study, we report the case of a hypokalemic patient with severe rebound hyperkalemia, which occurred as a result of barbiturate coma therapy administered for TBI treatment. PMID:27857927

  18. Mechanisms and assessment of statin-related muscular adverse effects.

    PubMed

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-09-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.

  19. Pharmacogenomics of statins: understanding susceptibility to adverse effects

    PubMed Central

    Kitzmiller, Joseph P; Mikulik, Eduard B; Dauki, Anees M; Murkherjee, Chandrama; Luzum, Jasmine A

    2016-01-01

    Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes), statin efficacy (eg, drug targets and pathways), and end-organ toxicity (eg, myopathy pathways) highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy. PMID:27757045

  20. Adverse effects of common medications on male fertility.

    PubMed

    Samplaski, Mary K; Nangia, Ajay K

    2015-07-01

    An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic-pituitary-gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility.

  1. Energy drink use and adverse effects among emergency department patients.

    PubMed

    Nordt, Sean Patrick; Vilke, Gary M; Clark, Richard F; Lee Cantrell, F; Chan, Theodore C; Galinato, Melissa; Nguyen, Vincent; Castillo, Edward M

    2012-10-01

    Energy drink usage is common and contains caffeine or other stimulants. We evaluated demographics, prevalence, reasons and adverse effects with consuming energy beverages. Cross-sectional study of a convenience sample of patients recruited from two San Diego Emergency Departments from January to December 2009. One-thousand-two-hundred-ninety-eight subjects participated of which 52.6% were male. Ethnicity: Caucasian 48.3%, African American 17%, Hispanic 18%, Other 16.7%. Age ranges: 18-29 years (38.4%), 30-54 years (49.6%) and greater than 55 years (12%). Reasons for use: 57% to "increase energy", 9.5% for studying/work projects, 2.4% while prolonged driving, improve sports performance 2%, with ethanol 6.3%, "other" reasons 22.1%. Adverse reactions reported by 33.5% (429) patients. Two-hundred-eighty report feeling "shaky/jittery", insomnia 136, palpitations 150, gastrointestinal upset 82, headache 68, chest pain 39, and seizures in 6. Eighty-five patients reported co-ingestion with illicit "stimulants" including cocaine and methamphetamine. We identified one-third of patients reported at least one adverse effect. Whilst most were not severe, a small number were serious e.g., seizures. In addition, some report purposely ingesting with illicit drugs.

  2. Distinguishing hazards and harms, adverse drug effects and adverse drug reactions : implications for drug development, clinical trials, pharmacovigilance, biomarkers, and monitoring.

    PubMed

    Aronson, Jeffrey K

    2013-03-01

    The terms 'adverse drug effects' and 'adverse drug reactions' are commonly used interchangeably, but they have different implications. Adverse drug reactions arise when a compound (e.g. a drug or metabolite, a contaminant or adulterant) is distributed in the same place as a body tissue (e.g. a receptor, enzyme, or ion channel), and the encounter results in an adverse effect (a physiological or pathological change), which results in a clinically appreciable adverse reaction. Both the adverse effect and the adverse reaction have manifestations by which they can be recognized: adverse effects are usually detected by laboratory tests (e.g. biochemical, haematological, immunological, radiological, pathological) or by clinical investigations (e.g. endoscopy, cardiac catheterization), and adverse reactions by their clinical manifestations (symptoms and/or signs). This distinction suggests five scenarios: (i) adverse reactions can result directly from adverse effects; (ii) adverse effects may not lead to appreciable adverse reactions; (iii) adverse reactions can occur without preceding adverse effects; (iv) adverse effects and reactions may be dissociated; and (v) adverse effects and reactions can together constitute syndromes. Defining an adverse drug reaction as "an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product" suggests a definition of an adverse drug effect: "a potentially harmful effect resulting from an intervention related to the use of a medicinal product, which constitutes a hazard and may or may not be associated with a clinically appreciable adverse reaction and/or an abnormal laboratory test or clinical investigation, as a marker of an adverse reaction."

  3. Adverse health effects of anabolic-androgenic steroids.

    PubMed

    van Amsterdam, Jan; Opperhuizen, Antoon; Hartgens, Fred

    2010-06-01

    Anabolic-androgenic steroids (AAS) are synthetic drugs derived from testosterone. Illegally, these drugs are regularly self-administered by body builders and power lifters to enhance their sportive performance. Adverse side effects of AAS include sexual dysfunction, alterations of the cardiovascular system, psyche and behavior, and liver toxicity. However, severe side effects appear only following prolonged use of AAS at high dose and their occurrence is limited. Occasionally, AAS abuse may be linked to certain social and psychological traits of the user, like low self-esteem, low self-confidence, suffered hostility, childhood conduct disorder, and tendency to high-risk behavior. The overwhelming stereotype about AAS is that these compounds cause aggressive behavior in males. However, the underlying personality traits of a specific subgroup of the AAS abusers, who show aggression and hostility, may be relevant, as well. Use of AAS in combination with alcohol largely increases the risk of violence and aggression. The dependence liability of AAS is very low, and withdrawal effects are relatively mild. Based on the scores for acute and chronic adverse health effects, the prevalence of use, social harm and criminality, AAS were ranked among 19 illicit drugs as a group of drugs with a relatively low harm.

  4. Macrophages are involved in hexachlorobenzene-induced adverse immune effects

    SciTech Connect

    Ezendam, Janine . E-mail: Janine.Ezendam@rivm.nl; Kosterman, Kevin; Spijkerboer, Henneke; Bleumink, Rob; Hassing, Ine; Rooijen, Nico van; Vos, Joseph G.; Pieters, Raymond

    2005-11-15

    Hexachlorobenzene (HCB) is a persistent environmental pollutant that causes adverse immune effects in man and rat. The Brown Norway (BN) rat is very susceptible to HCB-induced immunopathology and oral exposure causes inflammatory skin and lung lesions, splenomegaly, lymph node (LN) enlargement, and increased serum levels of IgE and anti-ssDNA IgM. T cells play an important role but do not account for all adverse effects induced by HCB. Macrophages are probably also important and the relationship between macrophages and T cells was further investigated. To eliminate macrophages clodronate-liposomes were used. Furthermore, a kinetic study was performed to obtain insight in the early phase of the HCB-induced immune response. Also, experiments were performed to detect specific memory T cells. Therefore, an adoptive transfer study was performed. Our results indicate that macrophages are indeed involved in HCB-induced skin lesions, lung eosinophilia, and elevation of IgM against ssDNA. Kinetics showed that both skin and lung lesions appeared early after exposure. Moreover, immune effects could not be adaptively transferred. Thus, both macrophages and T cells are involved in HCB-induced immune effects but HCB exposure does not lead to specific T cell sensitization. Presumably, HCB exposure induces macrophage activation, thereby generating adjuvant signals that polyclonally stimulate T cells. Together, these events may lead to the observed immunopathology in BN rats.

  5. Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products

    PubMed Central

    Bersani, F. Saverio; Coviello, Marialuce; Imperatori, Claudio; Francesconi, Marta; Hough, Christina M.; Valeriani, Giuseppe; De Stefano, Gianfranco; Bolzan Mariotti Posocco, Flaminia; Santacroce, Rita; Minichino, Amedeo; Corazza, Ornella

    2015-01-01

    Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs) as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs) often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications. PMID:26457296

  6. [Progresses on adverse health effects of automobile exhaust].

    PubMed

    Cheng, Yibin; Jin, Yinlong; Liu, Yingchun

    2003-09-01

    The progresses on the latest studies at home and abroad on adverse health effects of automobile exhaust were reviewed in this paper. Particulates and poisonous gases from automobile exhaust were considered to be harmful to respiratory system, immune system and reproductive system. It showed that increased prevalence of respiratory disease (e.g. chronic bronchitis and asthma), and decreased lung function, immunity were associated with automobile exhaust. The carcinogenic potential from the exposure to automobile exhausts needs to be further explored because the carcinogenesis is multifactorial.

  7. Adverse effects of antiretroviral therapy for HIV infection.

    PubMed

    Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

    2004-01-20

    Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

  8. Effects of renal perfusion pressure on renal medullary hydrogen peroxide and nitric oxide production.

    PubMed

    Jin, Chunhua; Hu, Chunyan; Polichnowski, Aaron; Mori, Takefumi; Skelton, Meredith; Ito, Sadayoshi; Cowley, Allen W

    2009-06-01

    Studies were designed to determine the effects of increases of renal perfusion pressure on the production of hydrogen peroxide (H(2)O(2)) and NO(2)(-)+NO(3)(-) within the renal outer medulla. Sprague-Dawley rats were studied with either the renal capsule intact or removed to ascertain the contribution of changes of medullary blood flow and renal interstitial hydrostatic pressure on H(2)O(2) and NO(2)(-)+NO(3)(-) production. Responses to three 30-minute step changes of renal perfusion pressure (from approximately 85 to approximately 115 to approximately 145 mm Hg) were studied using adjustable aortic occluders proximal and distal to the left renal artery. Medullary interstitial H(2)O(2) determined by microdialysis increased at each level of renal perfusion pressure from 640 to 874 to 1593 nmol/L, as did H(2)O(2) urinary excretion rates, and these responses were significantly attenuated by decapsulation. Medullary interstitial NO(2)(-)+NO(3)(-) increased from 9.2 to 13.8 to 16.1 mumol/L, with parallel changes in urine NO(2)(-)+NO(3)(-), but decapsulation did not significantly blunt these responses. Over the range of renal perfusion pressure, medullary blood flow (laser-Doppler flowmetry) rose approximately 30% and renal interstitial hydrostatic pressure rose from 7.8 to 19.7 cm H(2)O. Renal interstitial hydrostatic pressure and the natriuretic and diuretic responses were significantly attenuated with decapsulation, but medullary blood flow was not affected. The data indicate that pressure-induced increases of H(2)O(2) emanated largely from increased tubular flow rates to the medullary thick-ascending limbs of Henle and NO largely from increased medullary blood flow to the vasa recta. The parallel pressure-induced increases of H(2)O(2) and NO indicate a participation in shaping the "normal" pressure-natriuresis relationship and explain why an imbalance in either would affect the blood pressure salt sensitivity.

  9. Adverse effects of bisphenol A on male reproductive function.

    PubMed

    Manfo, Faustin Pascal Tsagué; Jubendradass, Rajamanickam; Nantia, Edouard Akono; Moundipa, Paul Fewou; Mathur, Premendu Prakash

    2014-01-01

    BPA is a ubiquitous environmental contaminant, resulting mainly from manufacturing,use or disposal of plastics of which it is a component, and the degradation of industrial plastic-related wastes. Growing evidence from research on laboratory animals, wildlife, and humans supports the view that BPA produces an endocrine disrupting effect and adversely affects male reproductive function. To better understand the adverse effects caused by exposure to BPA, we performed an up-to-date literature review on the topic, with particular emphasis on in utero exposure, and associated effects on spermatogenesis, steroidogenesis, and accessory organs.BPA studies on experimental animals show that effects are generally more detrimental during in utero exposure, a critical developmental stage for the embryo. BPA has been found to produce several defects in the embryo, such as feminization of male fetuses, atrophy of the testes and epididymides, increased prostate size, shortening of AGD, disruption of BTB, and alteration of adult sperm parameters (e.g.,sperm count, motility, and density). BPA also affects embryo thyroid development.During the postnatal and pubertal periods and adulthood, BPA affects the hypothalamic-pituitary-testicular axis by modulating hormone (e.g., LH and FSH,androgen and estrogen) synthesis, expression and function of respective receptors(ER, AR). These effects alter sperm parameters. BPA also induces oxidative stress in the testis and epididymis, by inhibiting antioxidant enzymes and stimulating lipid peroxidation. This suggests that employing antioxidants may be a promising strategy to relieve BPA-induced disturbances.Epidemiological studies have also provided data indicating that BPA alters male reproductive function in humans. These investigations revealed that men occupationally exposed to BPA had high blood/urinary BPA levels, and abnormal semen parameters. BPA-exposed men also showed reduced libido and erectile ejaculatory difficulties; moreover, the

  10. Adverse Effects Associated with Protein Intake above the Recommended Dietary Allowance for Adults.

    PubMed

    Delimaris, Ioannis

    2013-01-01

    Background. While high-protein consumption-above the current recommended dietary allowance for adults (RDA: 0.8 g protein/kg body weight/day)-is increasing in popularity, there is a lack of data on its potential adverse effects. Objective. To determine the potential disease risks due to high protein/high meat intake obtained from diet and/or nutritional supplements in humans. Design. Review. Subjects. Healthy adult male and female subjects. Method. In order to identify relevant studies, the electronic databases, Medline and Google Scholar, were searched using the terms:"high protein diet," "protein overconsumption," "protein overuse," and "high meat diet." Papers not in English were excluded. Further studies were identified by citations in retrieved papers. Results. 32 studies (21 experimental human studies and 11 reviews) were identified. The adverse effects associated with long-term high protein/high meat intake in humans were (a) disorders of bone and calcium homeostasis, (b) disorders of renal function, (c) increased cancer risk, (d) disorders of liver function, and (e) precipitated progression of coronary artery disease. Conclusions. The findings of the present study suggest that there is currently no reasonable scientific basis in the literature to recommend protein consumption above the current RDA (high protein diet) for healthy adults due to its potential disease risks. Further research needs to be carried out in this area, including large randomized controlled trials.

  11. Adverse effects of outdoor pollution in the elderly.

    PubMed

    Simoni, Marzia; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  12. Adverse effects of outdoor pollution in the elderly

    PubMed Central

    Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  13. Effect of tolazoline on renal function in newborn puppies.

    PubMed

    John, E G; Bhat, R; Assadi, F K; Vidyasagar, D; Fornell, L

    1986-01-01

    Tolazoline is used in pulmonary hypertension and hypoperfusion syndrome during the neonatal period. Some of the side effects of tolazoline are hypotension, bleeding disorders and renal dysfunction. The present study was designed to investigate the effect of hypoxia and tolazoline on renal function in newborn puppies. The data in normal animals administered tolazoline alone did not reveal any statistically significant changes in blood pressure or in renal function. In the hypoxia group changes in renal function were noticed in spite of normal blood pressure. When tolazoline was administered to the hypoxic animals, a marked decrease in blood pressure resulted. Indeed, changes in renal function were more profound in the hypoxic animals receiving tolazoline than in hypoxic animals not receiving tolazoline, even though some of the renal functional values did not reach statistical significance.

  14. Adverse effects of gentamicin in scarlet macaws and galahs.

    PubMed

    Flammer, K; Clark, C H; Drewes, L A; Wilson, R C; Fiorello-Barrett, J

    1990-03-01

    The adverse effects of administration of gentamicin (5 mg/kg of body weight, IM, q 12 h) for 7 days were studied in healthy scarlet macaws (Ara macao) and galahs (Eolophus roseicapillus; cockatoos). Polydipsia and polyuria developed in each species, but were greater and persisted longer in the cockatoos. Peak water intake in the cockatoos more than quadrupled, and remained increased for 23 days after cessation of gentamicin administration. Plasma aspartate transaminase activity increased significantly (P less than 0.05) after treatment in the macaws, and plasma aspartate transaminase and lactate dehydrogenase activities increased in the cockatoos. Single IM administration of gentamicin (5 mg/kg) resulted in mean (+/- SEM) plasma concentration of 20.6 (+/- 1.85) micrograms/ml at 0.5 hour for either species of birds. There were no significant differences between mean plasma gentamicin concentrations for cockatoos and macaws at any time after drug administration, except at 12 hours, when values for cockatoos were significantly (P less than 0.05) greater than those for macaws. The elimination half-life for gentamicin after IM administration of 5 and 10 mg/kg was 1.17 and 1.07 hours, respectively, for macaws and 1.23 and 1.44 hours, respectively, for cockatoos. Correlation between drug disposition and adverse side effects could not be detected.

  15. Adverse health effects of high-effort/low-reward conditions.

    PubMed

    Siegrist, J

    1996-01-01

    In addition to the person-environment fit model (J. R. French, R. D. Caplan, & R. V. Harrison, 1982) and the demand-control model (R. A. Karasek & T. Theorell, 1990), a third theoretical concept is proposed to assess adverse health effects of stressful experience at work: the effort-reward imbalance model. The focus of this model is on reciprocity of exchange in occupational life where high-cost/low-gain conditions are considered particularly stressful. Variables measuring low reward in terms of low status control (e.g., lack of promotion prospects, job insecurity) in association with high extrinsic (e.g., work pressure) or intrinsic (personal coping pattern, e.g., high need for control) effort independently predict new cardiovascular events in a prospective study on blue-collar men. Furthermore, these variables partly explain prevalence of cardiovascular risk factors (hypertension, atherogenic lipids) in 2 independent studies. Studying adverse health effects of high-effort/low-reward conditions seems well justified, especially in view of recent developments of the labor market.

  16. Pharmacovigilance, risks and adverse effects of self-medication.

    PubMed

    Montastruc, Jean-Louis; Bondon-Guitton, Emmanuelle; Abadie, Delphine; Lacroix, Isabelle; Berreni, Aurélia; Pugnet, Grégory; Durrieu, Geneviève; Sailler, Laurent; Giroud, Jean-Paul; Damase-Michel, Christine; Montastruc, François

    2016-04-01

    Self-medication means resorting to one or more drugs in order to treat oneself without the help of a doctor. This phenomenon is developing fast. In this review, we will discuss the main definitions of self-medication; we will then present a few important characteristics of this therapeutic practice: prevalence, reasons, populations involved and drugs used. Whilst the theoretical risks of self-medication have been abundantly discussed in the literature (adverse effects, interactions, product, dosage or treatment duration errors, difficulty in self-diagnosis, risk of addiction or abuse…), there is in fact very little detailed pharmacovigilance data concerning the characteristics and the consequences of this usage in real life. This study therefore describes the all too rare data that is available: patients, clinical characteristics, "seriousness" and drugs involved in the adverse effects of self-medication. It also discusses leads to be followed in order to minimize medication risks, which are obviously not well known and clearly not sufficiently notified.

  17. Symptomatic sinus bradycardia: A rare adverse effect of intravenous ondansetron

    PubMed Central

    Moazzam, Md Shahnawaz; Nasreen, Farah; Bano, Shahjahan; Amir, Syed Hussain

    2011-01-01

    Ondansetron is a serotonin receptor antagonist which has been used frequently to reduce the incidence of post-operative nausea and vomiting in laparoscopic surgery. It has become very popular drug for the prevention of post-operative nausea and vomiting due to its superiority in-terms of efficacy as well as lack of side effects and drug interactions. Although cardiovascular adverse effects of this drug are rare, we found a case of symptomatic sinus bradycardia in a 43-year-old female patient, going for laparoscopic cholecystectomy, who developed the same after she was given intravenous ondansetron in operation theater during premedication. Hence, we report this case, as the rare possibility of encountering bradycardia effect after intravenous administration of ondansetron should be born in mind. PMID:21655029

  18. Possible adverse effects of frying with vegetable oils.

    PubMed

    Dobarganes, Carmen; Márquez-Ruiz, Gloria

    2015-04-01

    The question of whether heated fats in the diet may be detrimental to health is nowadays of the upmost concern, but finding an answer is not easy and requires careful consideration of different aspects of lipid oxidation. This review is divided into two sections. The first part deals with the nature of the new compounds formed at high temperature in the frying process as well as their occurrence in the diet while the second part focuses on their possible nutritional and physiological effects. Oxidation products present in abused frying fats and oils are the compounds most suspected of impairing the nutritional properties of the oils or involving adverse physiological effects. The recent studies on their health implications include those related to their fate and those focused on their effects in metabolic pathways and the most prevalent diseases.

  19. [Surgical renal biopsies: technique, effectiveness and complications].

    PubMed

    Pinsach Elías, L; Blasco Casares, F J; Ibarz Servió, L; Valero Milián, J; Areal Calama, J; Bucar Terrades, S; Saladié Roig, J M

    1991-01-01

    Retrospective study made on 140 renal surgical biopsies (RSB) performed throughout the past 4 years in our Unit. The technique's effectiveness and morbidity are emphasized and the surgical technique and type of anaesthesia described. The sample obtained was enough to perform an essay in 100% cases, and a diagnosis was reached in 98.5%. Thirty-nine patients (27.8%) presented complications, 13 (9.2%) of which were directly related to the surgical technique. No case required blood transfusion and no deaths were reported. The type of anaesthesia used was: local plus sedation in 104 (74.2%) cases, rachianaesthesia in 10 (7.1%) and general in 26 (18.5%). The same approach was used in all patients: minimal subcostal lumbotomy, using Wilde's forceps to obtain the samples. It is believed that RSB is a highly effective, low mortality procedure, easy and quick to perform, and suitable for selected patients.

  20. Thiazolidinediones and their fluid-related adverse effects: facts, fiction and putative management strategies.

    PubMed

    Karalliedde, Janaka; Buckingham, Robin E

    2007-01-01

    Thiazolidinediones (TZDs) or glitazones are agents that are widely used for the treatment of type 2 diabetes mellitus. These drugs have a multitude of therapeutic effects including reduction in insulin resistance and hyperglycaemia, anti-inflammatory effects and amelioration of hypertension, microalbuminuria and hepatic steatosis. The TZD molecular target, peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear transcription factor, is expressed diffusely in humans, including many tissues comprising the cardiovascular and renal systems. This suggests a potential for TZDs to elicit perturbing effects on these systems, which are independent of their effects on glucose and lipid metabolism. One of the most common adverse effects of TZDs is fluid retention, which can result in, or exacerbate, oedema and congestive heart failure (CHF). The frequency of peripheral oedema is approximately 5% when TZDs are used in mono- or combination oral therapy, and about 15% when used with insulin. Patients with type 2 diabetes are at high risk of myriad morbid complications, including CHF. The development of CHF, particularly in the elderly, is a harbinger of premature mortality. TZD-induced oedema is largely peripheral, may have its origins in changes in haemodynamics, with some contribution from molecules, which regulate cell and tissue permeability (e.g. vascular endothelial growth factor and protein kinase Cbeta), and remains the preponderant manifestation of TZD-induced fluid retention even in those with existing heart failure. Preclinical and pilot clinical data attest to the fact that at least part of the fluid retention derives from a direct effect of TZDs on sodium reabsorption via the renal medullary collecting duct, a mechanism that is sensitive to diuretic agents that have this nephron segment as their site of action, in whole or in part (spironolactone, amiloride and hydrochlorothiazide). Our review suggests various potential clinical strategies by which

  1. Adverse testicular effects of Botox® in mature rats

    SciTech Connect

    Breikaa, Randa M.; Mosli, Hisham A.; Nagy, Ayman A.; Abdel-Naim, Ashraf B.

    2014-03-01

    Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicular function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause. - Highlights: • Botox® injections are the trend nowadays, for both medical and non-medical uses. • They were recently suggested for cryptorchidism and

  2. Renal effects of uranium in drinking water.

    PubMed Central

    Kurttio, Päivi; Auvinen, Anssi; Salonen, Laina; Saha, Heikki; Pekkanen, Juha; Mäkeläinen, Ilona; Väisänen, Sari B; Penttilä, Ilkka M; Komulainen, Hannu

    2002-01-01

    Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L. PMID:11940450

  3. Effect of renal impairment on the pharmacokinetics of grepafloxacin.

    PubMed

    Efthymiopoulos, C; Bramer, S L; Maroli, A; Gambertoglio, J G

    1997-01-01

    Grepafloxacin is mainly (approximately 90%) excreted by nonrenal mechanisms. The effect of renal impairment on the pharmacokinetics of grepafloxacin was evaluated in an open-label study involving 20 adults, 15 of whom had some degree of renal impairment (creatinine clearance 7.5 to 64.0 ml/min). Of these 15, 3 had mild renal impairment, 6 had moderate renal impairment, and 6 had severe renal impairment. Grepafloxacin 400 mg was administered orally once daily for 7 days, and pharmacokinetic parameters were measured on days 1 and 7. The results show that both renal clearance and the amount of grepafloxacin excreted unchanged in urine, on day 1 and day 7, were significantly lower in individuals with severe renal impairment compared with those who were healthy. Renal clearance was 0.50 +/- 0.05 ml/min/kg in healthy individuals vs 0.15 +/- 0.05 ml/min/kg in patients with severe renal impairment on day 1, while the corresponding values on day 7 were 0.46 +/- 0.04 ml/min/kg vs 0.14 +/- 0.08 ml/min/kg, respectively. The percentage of grepafloxacin excreted unchanged in urine on day 1 was 5.1 +/- 3.0 in the healthy individuals and 1.5 +/- 0.7 in those with severe renal impairment. On day 7, the corresponding values were 7.9 +/- 1.9 and 2.9 +/- 2.2. No other significant pharmacokinetic differences occurred between the 2 groups. Accumulation during multiple dose administration did not vary with the degree of renal impairment. We conclude that the pharmacokinetics of grepafloxacin are not significantly different in individuals with varying degrees of renal impairment. Hence, dose adjustment is not necessary during treatment of patients with renal dysfunction.

  4. Denosumab. Limited efficacy in fracture prevention, too many adverse effects.

    PubMed

    2011-06-01

    The standard drug for postmenopausal osteoporotic women with a high risk of fracture is alendronic acid, used in conjunction with non-drug measures. There are no drugs with demonstrated efficacy on the risk of fracture in castrated men with prostate cancer. Denosumab, a monoclonal antibody that inhibits a cytokine acting mainly on bone cells and lymphocytes, has been authorised in the European Union for use in both these settings. There are no trials comparing denosumab versus alendronic acid for symptomatic fracture prevention. In two trials involving 1189 and 504 women, the incidence of clinical fractures, recorded as simple adverse effects, did not differ significantly between the groups. In a placebo-controlled trial in about 7900 elderly osteoporotic women, denosumab significantly reduced the incidence of symptomatic vertebral fractures (0.8% versus 2.6% after 3 years) and hip fractures (0.7% versus 1.2%). An indirect comparison, providing weak evidence, suggests that denosumab is less effective than alendronic acid. In a placebo-controlled trial in 1468 castrated men with prostate cancer, denosumab did not reduce the incidence of symptomatic fractures after 3 years. Only the incidence of vertebral fractures, detected on routine radiographs, showed a statistically significant decline (1.5% versus 3.5%). Denosumab has numerous adverse effects. In placebo-controlled trials, this monoclonal antibody was associated with a higher incidence of deep-seated infections such as endocarditis, cancer, and skin rash. More data are needed on the risk of pancreatitis, long-term bone disorders (atypical fractures, delayed fracture healing, osteonecrosis of the jaw), hypocalcaemia and cataracts, all of which were reported in clinical trials. In practice, denosumab is not sufficiently effective to outweigh its established and potential risks in postmenopausal osteoporotic women or in castrated men with prostate cancer.

  5. Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study

    PubMed Central

    Marston, Louise; Walters, Kate; Geddes, John R.; King, Michael; Osborn, David P. J.

    2016-01-01

    0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31–2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47–2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24–2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06–1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects. Conclusions Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options. PMID:27483368

  6. Does Cannabidiol Protect Against Adverse Psychological Effects of THC?

    PubMed

    Niesink, Raymond J M; van Laar, Margriet W

    2013-10-16

    The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD). A literature search was performed in the bibliographic databases PubMed, PsycINFO, and Web of Science using the keyword "cannabidiol." After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone's individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users.

  7. Short-Term Effects of Ankaferd Hemostat for Renal Artery Embolization: An Experimental Study

    SciTech Connect

    Ozbek, Orhan; Acar, Kadir; Koc, Osman; Saritas, Kadir; Toy, Hatice; Solak, Yalcin; Ozbek, Seda; Kucukapan, Ahmet; Guler, Ibrahim; Gaipov, Abduzhappar; Turk, Suleyman; Haznedaroglu, Ibrahim Celaleddin

    2013-04-15

    Renal artery embolization (RAE) is a minimally invasive therapeutic technique that is utilized in a number of disorders. Ankaferd is a novel hemostatic agent with a new mechanism of action independent of clotting factors. We used Ankaferd for RAE in a sheep model. Seven adult female sheep were included in the study. Selective renal arteriogram using 5-F diagnostic catheter was performed to make sure that each kidney was fed by a single renal artery and the animal had normal renal vasculature. Coaxial 2.7-F microcatheter was advanced to the distal main renal artery. Under fluoroscopic guidance, 2 mL of Ankaferd mixed with 2 mL of nonionic iodinated contrast agent was slowly injected. Fluoroscopy was used to observe the deceleration of flow and stagnation. Control renal angiograms were performed just after embolization. After the procedure, the animals were observed for 1 day and then sacrificed with intravenous sodium thiopental. The technical success was observed in seven of the seven animals.. After embolization procedure, none of the animals died or experienced a major systemic adverse event. On macroscopic examination of the embolized kidneys, thrombus at the level of main renal artery formed after Ankaferd embolization was more compact compared with the thrombi that was not Ankaferd-associated, which was observed elsewhere. Microscopically, majority of the renal tubular cells (80-90 %) were necrotic, and there was epithelial cell damage in a small portion of the cells (10-20 %). RAE was safe and effective in the short-term with Ankaferd in studied animals. Further studies should be conducted to better delineate the embolizing potential of this novel hemostatic agent.

  8. Immune checkpoint inhibitors renal side effects and management.

    PubMed

    Rassy, Elie El; Kourie, Hampig R; Rizkallah, Jamale; Karak, Fadi El; Hanna, Colette; Chelala, Dania N; Ghosn, Marwan

    2016-12-01

    The choice of immunotherapy in the treatment of cancer has improved the prognosis of many patients affected by various malignancies. The high expectations foreseen with immunotherapy have led to fast approvals despite the incomplete understanding of the toxicity profiles in the different organs, including the kidneys. The high prevalence of chronic kidney disease in cancer patients complicates the issue further and requires a better knowledge of the renal safety profile to ensure an optimal safe treatment. This review summarizes the present knowledge of renal adverse events secondary to immune checkpoint inhibitors and discusses their pathophysiology, clinical presentation and adequate management. We also advocate the need for a multidisciplinary approach in patients with immune-related toxic adverse events.

  9. The Adverse Effects of Air Pollution on the Nervous System

    PubMed Central

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  10. Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism

    PubMed Central

    Brennan-Speranza, Tara C.; Henneicke, Holger; Gasparini, Sylvia J.; Blankenstein, Katharina I.; Heinevetter, Uta; Cogger, Victoria C.; Svistounov, Dmitri; Zhang, Yaqing; Cooney, Gregory J.; Buttgereit, Frank; Dunstan, Colin R.; Gundberg, Caren; Zhou, Hong; Seibel, Markus J.

    2012-01-01

    Long-term glucocorticoid treatment is associated with numerous adverse outcomes, including weight gain, insulin resistance, and diabetes; however, the pathogenesis of these side effects remains obscure. Glucocorticoids also suppress osteoblast function, including osteocalcin synthesis. Osteocalcin is an osteoblast-specific peptide that is reported to be involved in normal murine fuel metabolism. We now demonstrate that osteoblasts play a pivotal role in the pathogenesis of glucocorticoid-induced dysmetabolism. Osteoblast-targeted disruption of glucocorticoid signaling significantly attenuated the suppression of osteocalcin synthesis and prevented the development of insulin resistance, glucose intolerance, and abnormal weight gain in corticosterone-treated mice. Nearly identical effects were observed in glucocorticoid-treated animals following heterotopic (hepatic) expression of both carboxylated and uncarboxylated osteocalcin through gene therapy, which additionally led to a reduction in hepatic lipid deposition and improved phosphorylation of the insulin receptor. These data suggest that the effects of exogenous high-dose glucocorticoids on insulin target tissues and systemic energy metabolism are mediated, at least in part, through the skeleton. PMID:23093779

  11. Parenteral Lipid Tolerance and Adverse Effects: Fat Chance for Trouble?

    PubMed

    Wanten, Geert J A

    2015-09-01

    Lipid emulsions (LEs) are indispensable sources of fuel calories and (essential) fatty acids (FAs) in modern parenteral nutrition formulations. The use of LE, however, also remains associated with the development of adverse effects. Intolerance for LE mostly becomes apparent upon the development of patient complaints or disturbed blood function tests, mainly of the liver. These issues may be associated with the composition, stability, or the infusion rate of the emulsion. Also, altered balances of (anti)oxidants or the presence or absence of protective or toxic bioactive agents such as phytosterols and tocopherol in LE may lead to complications, especially in already vulnerable patients with an inflammatory condition. While the oldest available LEs are based on pure soybean oil (SO-LE), rich in the proinflammatory ω-6 polyunsaturated fatty acid linoleic acid, more recent next-generation LEs where alternative FA sources such as olive and fish oil (partially) replace soybean oil to lower the content of linoleic acid seem safe and effective. Especially LEs containing fish oil (FO-LE) have less proinflammatory characteristics that promise to convey beneficial effects on immune system and organ functions, although much of the available evidence awaits more robust clinical validation.

  12. Identification and Characterization of Adverse Effects in 21st Century Toxicology

    EPA Science Inventory

    The ILSI Health and Environmental Sciences Institute Project Committee on Distinguishing Adverse from Non-Adverse / Adaptive Effects held a workshop in May 2011 to discuss approaches to identifying adverse effects in the context of the 2007 NRC committee report titled “Toxicity T...

  13. Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

    PubMed

    St Louis, Erik K; Louis, Erik K

    2009-06-01

    The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, "neurotoxic" adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drug-sparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

  14. CORAL: model for no observed adverse effect level (NOAEL).

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Pizzo, Fabiola; Lombardo, Anna; Gadaleta, Domenico; Benfenati, Emilio

    2015-08-01

    The in vivo repeated dose toxicity (RDT) test is intended to provide information on the possible risk caused by repeated exposure to a substance over a limited period of time. The measure of the RDT is the no observed adverse effect level (NOAEL) that is the dose at which no effects are observed, i.e., this endpoint indicates the safety level for a substance. The need to replace in vivo tests, as required by some European Regulations (registration, evaluation authorization and restriction of chemicals) is leading to the searching for reliable alternative methods such as quantitative structure-activity relationships (QSAR). Considering the complexity of the RDT endpoint, for which data quality is limited and depends anyway on the study design, the development of QSAR for this endpoint is an attractive task. Starting from a dataset of 140 organic compounds with NOAEL values related to oral short term toxicity in rats, we developed a QSAR model based on optimal descriptors calculated with simplified molecular input-line entry systems and the graph of atomic orbitals by the Monte Carlo method, using CORAL software. Three different splits into the training, calibration, and validation sets are studied. The mechanistic interpretation of these models in terms of molecular fragment with positive or negative contributions to the endpoint is discussed. The probabilistic definition for the domain of applicability is suggested.

  15. Adverse Effects of Psychotropic Medications in Children: Predictive Factors

    PubMed Central

    Ninan, Ajit; Stewart, Shannon L.; Theall, Laura A.; Katuwapitiya, Shehan; Kam, Chester

    2014-01-01

    Objective: Despite limited information related to efficacy in children, psychotropic medications are commonly prescribed as a first-line treatment for a range of psychiatric diagnoses in children in a variety of clinical settings. Usage has increased over the past three decades. Although psychotropic medications are often effective at treating psychiatric symptoms, the risk of adverse effects (AE) in children is unclear. The current research seeks to identify the mental health characteristics of those children at highest risk of experiencing potential AE from psychotropic medications. Methods: Psychotropic medication monitoring checklists were used to record possible AE for 99 pediatric clients in a tertiary mental health residential treatment centre for the duration of one to eight weeks. Client characteristics, including the number of diagnoses and behavioural variables, were explored for predictive value of potential AE observed. Results: Results showed that the total number of potential AE was positively predicted by the number of DSM-IV categories diagnosed, as well as behavioural symptoms of impulsiveness and uncooperativeness. Conclusions: The findings of this study indicate that the number of potential AE from psychotropic medications may be predictable based on client characteristics. Predicting this likelihood during initial assessment can be useful in directing and monitoring treatment, as well as preventing serious events related to medication use. PMID:25320615

  16. Acute effects of ethanol on renal folate clearance in rats

    SciTech Connect

    Eisenga, B.H.; McMartin, K.E.

    1986-03-05

    Studies of the renal clearance of folic acid in primates demonstrate net reabsorption of folate by a saturable system. The acute administration of ethanol to rats causes a significant increase in urinary folate excretion. The mechanism for this effect is unknown and thus the effect of acute administration of ethanol on the renal absorption and urinary clearance of folate was studied in rats. Folic acid was administered to male Sprague-Dawley rats via continuous intravenous infusion in doses ranging from 3-75 micromoles/kg and renal clearance relative to inulin was determined. The effects of various dose levels of ethanol on these parameters were then determined. At a dose of 15 micromoles/kg, the renal clearance of folate relative to that of inulin was about 0.65 mg/min. At a plasma ethanol level about 100 mg/dl, the renal clearance of folate was not markedly altered. These results suggests that there is net reabsorption of folate in the rat kidney and that moderate doses of ethanol have little effect on renal effect on renal folate reabsorption.

  17. Renal effects of immune checkpoint inhibitors.

    PubMed

    Izzedine, Hassan; Mateus, Christine; Boutros, Céline; Robert, Caroline; Rouvier, Philippe; Amoura, Zahir; Mathian, Alexis

    2016-12-26

    Recent advances in immune checkpoint inhibitor (ICPI) development have led to major improvements in oncology patient outcomes. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are two essential immune checkpoint receptors. Ipilimumab and tremelimumab (anti-CTLA-4-blocking antibodies) and pembrolizumab and nivolumab (antibodies targeting PD-1 receptors) have already been approved by US Food and Drug Administration in several malignancies. Two different forms of ICPI-induced renal damage have been identified, including acute (granulomatous) tubulointerstitial nephritis and immune complex glomerulonephritis. The observed acute renal damage can be reversed upon ICPI drug discontinuation and renal function can recover back to normal following the introduction of systemic corticosteroid treatment. Any delay in treating this complication could result in definitive and irreversible renal injury.

  18. Renal hemodynamic effects of relaxin in humans.

    PubMed

    Smith, Marie; Davison, John; Conrad, Kirk; Danielson, Lee

    2005-05-01

    Rat studies have convincingly demonstrated the essential role of the ovarian hormone relaxin in mediating gestational renal hemodynamic and osmoregulatory changes in that species. We describe a model in nonpregnant volunteers using exogenous hCG to stimulate the production and release of ovarian relaxin in order to assess renal hemodynamic responses. Women (n = 10) were serially studied +/- hCG stimulation during menstrual cycles with measurement of inulin, PAH, and neutral dextran clearances (to determine glomerular filtration rate [GFR], renal plasma flow [RPF], and glomerular porosity, respectively). Controls were women without ovarian function (n = 6) and men (n = 10). GFR and RPF were increased in the luteal phase compared to the follicular phase (15.3% increase in GFR, P < 0.005; 17.8% increase in RPF, P < 0.05). In controls, GFR and RPF were not significantly different between study occasions. Although exogenous hCG did not stimulate relaxin secretion in women without ovarian function or in men, it did so in normal women, but not into the pregnancy range. In no group were renal hemodynamics augmented by administered hCG. In naturally occurring cycles, increased serum relaxin is associated with augmented renal hemodynamics. As luteal stimulation with hCG failed to yield pregnancy relaxin levels, the use of exogenous relaxin for human administration is needed to further elucidate the renal vasodilatory properties of relaxin.

  19. Shocking Results on the Adverse Effects of CO2 Exposures

    NASA Technical Reports Server (NTRS)

    James, John T.

    2012-01-01

    Carbon dioxide (CO2) is released in large quantities from humans while they live and work in spacecraft or work outside the spacecraft during extravehicular activity (EVA). Removal of this anthropogenic pollutant requires major resources, and these resources increase dramatically as the levels of CO2 set to protect human health and performance are reduced. The current Spacecraft Maximum Allowable Concentration of CO2 aboard the ISS is 0.7% or 5.3 mmHg; however, according to Chits (mission action requests), NASA and its international partners have agreed to control CO2 levels to less than 4 mmHg. In the meantime, retrospective investigations attempting to associate crew symptoms with elevated CO2 levels over the life if the International Space Station (ISS) are underway to determine if this level is sufficient to protect against health and performance decrements. Anecdotal reports suggest that crewmembers are not able to perform complex tasks as readily in spaceflight as they were able during ground-based training. While physiological effects of CO2 have been studied for many decades, it is only recently that the effects of CO2 on higher reasoning capabilities have been studied. The initial results are shocking. For example, one study published in the respected journal Environmental Health Perspectives showed obvious adverse effects of CO2 exposures on higher reasoning at 1.9 mmHg. The implications and limitations of this study are paramount in determining future CO2 SMACs for human spaceflight, both aboard the ISS and in exploration-class missions. Key Words: carbon dioxide, spacecraft, air quality, toxic effects

  20. Adverse testicular effects of Botox® in mature rats.

    PubMed

    Breikaa, Randa M; Mosli, Hisham A; Nagy, Ayman A; Abdel-Naim, Ashraf B

    2014-03-01

    Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicular function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause.

  1. Enzymes approved for human therapy: indications, mechanisms and adverse effects.

    PubMed

    Baldo, Brian A

    2015-02-01

    Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.

  2. Adverse effects of lactational exposure to chlorpyrifos in suckling rats.

    PubMed

    Mansour, S A; Mossa, A H

    2010-02-01

    The present study was undertaken to evaluate the oxidative damage, biochemical and histopathological alterations in sucking rats whose mothers were exposed to the insecticide chlorpyrifos (CPF). Dams were administered CPF, via oral route. Doses equalled 0.01 mg kg(-1) body weight (b.wt.; acceptable daily intake, ADI), 1.00 mg kg(-1) b.wt. (no observed adverse effects level, NOAEL) and 1.35 mg kg(-1) b.wt. (1/100 lethal dose [LD(50)]) from postnatal day 1 until day 20 after delivery. At two high doses of CPF, the body weight gain and relative liver and kidney weight of suckling pups were significantly decreased. Exposure of the mothers to CPF caused increase in lipid peroxidation (LPO) and decrease in superoxide dismutase (SOD) and glutathione-s-transferase (GST) in lactating pups. CPF altered the level of the marker parameters related to the liver and kidneys. Consistent histological changes were found in the liver and kidneys of the subjected pups, especially at the higher doses. The results suggested that the transfer of CPF intoxication through the mother's milk has resulted in oxidative stress and biochemical and histopathological alterations in the suckling pups. The data of this study may be considered as a contribution to the problem of lactational transfer of the relatively less persistent OP pesticides, such as CPF.

  3. Second-Generation Antipsychotics and Extrapyramidal Adverse Effects

    PubMed Central

    Jakovcevski, Igor

    2014-01-01

    Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability. PMID:24995318

  4. Adverse cognitive effects of antiepileptic pharmacotherapy: Each additional drug matters.

    PubMed

    Witt, Juri-Alexander; Elger, Christian E; Helmstaedter, Christoph

    2015-11-01

    The study was set up to evaluate the impact of the total drug load of antiepileptic pharmacotherapy on cognition. Retrospective analyses were based on 834 patients with epilepsy who underwent a brief routine assessment of executive function and verbal memory (EpiTrack Plus) at our department. The total drug load was quantified in two ways: (1) number of concurrent antiepileptic drugs (AEDs) and (2) total drug load according to the defined daily dose (DDD) provided by the World Health Organization. The cognitive measures showed higher inverse correlations with the number of AEDs (executive function: r=-0.35, p<0.001; memory: r=-0.22, p<0.001) than with the total DDD (executive function: r=-0.27, p<0.001; memory: r=-0.17, p<0.001). Reanalysis with statistical control for disease severity hardly changed the aforementioned results. With each additional drug in polytherapy, we observed a significantly lower performance in executive function. In this regard an additional explorative approach revealed that regimens combining AEDs with favorable cognitive profiles were associated with higher cognitive performance. Correlations between indicators of disease severity and drug load indices were low: altogether explaining only up to 9% of the observed variance in drug load. The findings demonstrate a considerable adverse effect of a higher drug load on cognition, especially on executive functions. Simply counting the number of drugs may be sufficient as a rough estimate of the risk of side effects. However, the combination of AEDs with favorable cognitive profiles may attenuate the negative effect of the total drug load.

  5. Ropinirole: new indication. Restless legs: disproportionate adverse effects.

    PubMed

    2006-10-01

    (1) The restless legs syndrome consists of unpleasant sensory and motor symptoms of varying intensity in the lower limbs. Symptoms occur at rest, seated or lying down, are more intense in the evening and at night, and are relieved by moving the limb. This syndrome does not cause serious physical complications. When sleep disturbances occur, non drug methods should be tried first. (2) Ropinirole is a dopaminergic agonist initially marketed for the treatment of Parkinson's disease. It is the first drug to be approved for restless legs syndrome in France. (3) Three double-blind randomised placebo-controlled trials with similar designs showed minimal differences on a composite rating scale. After 12 weeks of treatment, ropinirole led to an improvement of about 3 points on a 40-point scale compared with placebo. (4) A 12-week double-blind randomised controlled trial and including patients who had "responded" to ropinirole showed a lower relapse rate in the group that continued to use ropinirole (32.6%) instead of switching to placebo (57.8%). However, we do not know if this was because of continued drug efficacy or a rebound effect in the placebo group. (5) The adverse effects of ropinirole in patients with restless legs syndrome had already been observed in the treatment of Parkinson's disease, and included nausea, vomiting, drowsiness, a sudden urge to sleep, syncope, hypotension, and hallucinations. (6) An increase in the severity of restless legs symptoms, typically seen with levodopa, was not evaluated in clinical trials of ropinirole. Some cases have nevertheless been reported. They describe the appearance of symptoms increasingly early in the evening, then in the afternoon, or as a rebound effect in the morning or the latter part of the night. Their intensity increases and can affect other parts of the body. (7) In practice, ropinirole has a negative risk-benefit balance in restless legs syndrome, which is a minor health disorder.

  6. Adverse Effects of Pesticides Residues on Biochemical Markers in Pakistani Tobacco Farmers

    PubMed Central

    Khan, Dilshad A; Bhatti, Mahwish M; Khan, Farooq A; Naqvi, Syed T; Karam, A

    2008-01-01

    Tobacco is an important cash crop of Pakistan and tremendous amount of irrational pesticides are being used to control insect growth. The frequency of plasma pesticide residues above acceptable daily intake (ADI) and its correlation with biochemical markers for assessment of adverse health effects in the tobacco farmers at district Sawabi, Pakistan was determined. Total 109 adult males consisting of 55 tobacco farmers exposed to pesticides and 54 controls were included. Pesticides residues in blood were analyzed on HPLC and GC-NPD. Plasma butyrylcholinesterase (BChE) was analyzed by Ellman's method. Biochemical markers including serum calcium, phosphorus, urea, creatinine, bilirubin and liver enzymes were measured on Selectra-E auto analyzer. The tobacco farmers had multiple pesticides residues above ADI in their blood consisting of 35 (63%) methomyl; 31 (56%) thiodicarb; 34(62%) cypermethrin; 27 (49%) Imidacloprid; 18 (32%) Methamidophos and 15 (27%) endosulfan. BChE activity was significantly decreased in the pesticides exposed farmers as compared to controls (P<0.001). Plasma biochemical markers including ALT, AST, CK, LDH and phosphate were significantly raised in the pesticides exposed farmers as compared to control group (P<0.001). Total pesticides residues revealed a significant positive correlation with AST (r=0.42), LDH(r= 0.47), ALT (r=0.20) and phosphorus (r=0.51). Excessive exposure to pesticide caused cytotoxic changes in the hepatic and renal biochemical markers which were positively correlated with pesticide residue. Hence these biomarkers might be used in addition to BChE activity for monitoring of adverse effects of pesticides on the health of farm workers. PMID:19079663

  7. Ziconotide: new drug. Limited analgesic efficacy, too many adverse effects.

    PubMed

    2008-10-01

    (1) When oral morphine does not relieve severe pain and when there is no specific treatment for the underlying cause, the first option is to try subcutaneous or intravenous administration. If this standard treatment fails or is poorly tolerated, intrathecal injection is usually preferred as the direct route to the central nervous system. However, one-quarter to one-half of patients still do not achieve adequate pain relief, and adverse effects are relatively frequent; (2) Ziconotide is not an opiate and is not related to the usual classes of drugs that interfere with nervous transmission in the posterior horn of the spinal cord. Marketing authorization has been granted for "severe, chronic pain in patients who require intrathecal analgesia". The Summary of Product Characteristics (SPC) recommends continuous infusion via an intrathecal catheter connected to a pump; (3) Clinical evaluation of ziconotide does not include any trials versus morphine in patients with nociceptive pain, or any trials versus tricyclic or antiepileptic drugs in patients with neurogenic pain; (4) In a trial in 220 patients in whom systemic morphine had failed, the mean pain score on a 100-mm visual analogue scale was 69.8 mm after three weeks on ziconotide, compared to 75.8 mm with placebo. This difference, although statistically significant, is clinically irrelevant. The proportion of "responders" (reduction of at least 30% in the initial pain score) was respectively 16.1% and 12.0% (no statistically significant difference); (5) The two other placebo-controlled trials included 112 patients with pain linked to cancer or HIV infection, and 257 patients with non-cancer pain. After a titration phase lasting 5 to 6 days, a combined analysis of the two trials showed that the mean pain score was 48.8 mm with ziconotide and 68.4 mm with placebo (statistically significant difference). However, many patients did not complete the titration phase. Efficacy also appeared to differ according to the type

  8. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    PubMed

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  9. The renal effects of SGLT2 inhibitors and a mini-review of the literature.

    PubMed

    Andrianesis, Vasileios; Glykofridi, Spyridoula; Doupis, John

    2016-12-01

    Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new and promising class of antidiabetic agents which target renal tubular glucose reabsorption. Their action is based on the blockage of SGLT2 sodium-glucose cotransporters that are located at the luminal membrane of tubular cells of the proximal convoluted tubule, inducing glucosuria. It has been proven that they significantly reduce glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus (T2DM). The glucosuria-induced caloric loss as well as the osmotic diuresis significantly decrease body weight and blood pressure, respectively. Given that SGLT2 inhibitors do not interfere with insulin action and secretion, their efficacy is sustained despite the progressive β-cell failure in T2DM. They are well tolerated, with a low risk of hypoglycemia. Their most frequent adverse events are minor: genital and urinal tract infections. Recently, it was demonstrated that empagliflozin presents a significant cardioprotective effect. Although the SGLT2 inhibitors' efficacy is affected by renal function, new data have been presented that some SGLT2 inhibitors, even in mild and moderate renal impairment, induce significant HbA1c reduction. Moreover, recent data indicate that SGLT2 inhibition has a beneficial renoprotective effect. The role of this review paper is to explore the current evidence on the renal effects of SGLT2 inhibitors.

  10. The renal effects of SGLT2 inhibitors and a mini-review of the literature

    PubMed Central

    Andrianesis, Vasileios; Glykofridi, Spyridoula; Doupis, John

    2016-01-01

    Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new and promising class of antidiabetic agents which target renal tubular glucose reabsorption. Their action is based on the blockage of SGLT2 sodium-glucose cotransporters that are located at the luminal membrane of tubular cells of the proximal convoluted tubule, inducing glucosuria. It has been proven that they significantly reduce glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus (T2DM). The glucosuria-induced caloric loss as well as the osmotic diuresis significantly decrease body weight and blood pressure, respectively. Given that SGLT2 inhibitors do not interfere with insulin action and secretion, their efficacy is sustained despite the progressive β-cell failure in T2DM. They are well tolerated, with a low risk of hypoglycemia. Their most frequent adverse events are minor: genital and urinal tract infections. Recently, it was demonstrated that empagliflozin presents a significant cardioprotective effect. Although the SGLT2 inhibitors’ efficacy is affected by renal function, new data have been presented that some SGLT2 inhibitors, even in mild and moderate renal impairment, induce significant HbA1c reduction. Moreover, recent data indicate that SGLT2 inhibition has a beneficial renoprotective effect. The role of this review paper is to explore the current evidence on the renal effects of SGLT2 inhibitors. PMID:28203358

  11. Differential renal function in unilateral renal injury: possible effects of radiopharmaceutical choice. [Rats

    SciTech Connect

    Taylor, A. Jr.; Lallone, R.

    1985-01-01

    An abnormal filtration fraction or a significant divergence between a kidney's ability to extract Tc-99m dimercaptosuccinic acid (DMSA) and other function parameters, such as the glomerular filtration rate (GFR) or the effective renal plasma flow (ERPF, could lead to different estimates of relative or absolute renal function, depending on the radiopharmaceutical administered. To evaluate this possible divergence, the authors measured the relative GFR (I-125 iothalamate), ERPF (I-131 hippurate), and Tc-99m DMSA accumulation in adult male Sprague-Dawley rats with unilateral ureteral obstruction or unilateral ischemia at various times after renal injury. The relative ERPF of the obstructed kidney was significantly greater than the relative GFR at all time periods studied; significant but less dramatic differences were noted comparing DMSA with GFR in obstruction and DMSA and ERPF with GRF in ischemia.

  12. [Usefulness and adverse effects of intrathecal metrizamide instillation (author's transl)].

    PubMed

    Masuzawa, H; Shimizu, H; Sano, K

    1979-08-01

    Radiographic quality as well as adverse effects of intrathecal metrizamide instillation was prospectively investigated in thirty-three clinical cases admitted to the department of neurosurgery, University of Tokyo Hospital, and Kantoh Teishin Hospital. Metrizamide CT cisternography was performed in fifteen cases using in most cases 10 ml of 170 mg I/ml solution through lumbar route. Eleven cases exhibited "normal" pattern CSF circulation and the remaining four, "delayed" pattern. Eight cases (53%) experienced headache, nausea, and/or vomiting several hours after the instillation. All of these belong to the "normal" pattern group. Four cases of "normal" pattern received electroencephalographic examinations before and after metrizamide instillation. Three revealed appearance of negative spike and slow wave burst or sharp waves one to twenty-four hours after the instillation, along with penetration of metrizamide into brain parenchyma. Diagnostic quality was interpreted as "good" in eleven cases. Small acoustic neurinoma, pituitary adenoma, arachnoid cyst, and subdural hygroma were diagnosed among others. Metrizamide ventriculography was done in four cases. No untoward effect of significance was attributed to metrizamide per se. Cervical myelograpy and/or CT myelography was done in fourteen cases using, in most cases, 10 ml of metrizamide 170 mgI/ml. Polytome tomography with metrizamide instillation through lateral cervical puncture was highly diagnostic, whereas, ordinary X-ray with lumbar instillation yielded less satisfactory results. CT myelography in cases of subarachnoid block required good consideration on instillation site and positioning of the patient. Six cases (50%) among twelve cases where metrizamide had run into the cranial cavity experienced headache, nausea, and/or vomiting to a lesser degree than those of cisterno graphy. Metrizamide is the first contrast agent ever made which can be safely introduced into human subarachnoid space, if administered

  13. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero G in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Four rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast, five of the seven remaining rats increased the fraction of the filtered sodium excreted and their urinary flow rate. Potassium excretion increased. End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause in the rat a decrease in distal tubular sodium and water reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis. The adequacy of other nonatrial volume control mechanisms in regulating renal salt and water conservation in opposition to the studied atrial-renal (Henry-Gauer) reflex of thoracic vascular distension is confirmed.

  14. Occupational exposure to lead: effects on renal function

    SciTech Connect

    Hong, C.D.; Hanenson, I.B.; Lerner, S.; Hammond, P.B.; Pesce, A.J.; Pollak, V.E.

    1980-10-01

    Although nephrotoxicity is common following exposure to lead, the dose-response relationship in adults with occupational exposure is not well understood because information is lacking on early nephrotoxic effects. By the time serum urea nitrogen and creatinine levels are elevated, renal damage may be advanced and not fully reversible. Detailed investigations of renal glomerular and tubular function were performed in six adults with occupational exposure to lead. In all patients, the serum creatinine and urea nitrogen concentrations were within the normal range. GFR was decreased in all but two. Glucose reabsorptive capacity (TmG) was decreased in all, and this decrease was disproportionately greater than expected from the reduced GFR in all but one. Normal values for renal plasma flow (RFP) were observed in four of the six, and for rho-aminohippurate (PAH) secretory capacity (TmPAh) in all but one. Bicarbonate reabsorptive capacity (TmHCO3) and urinary excretion of beta2-microglobulin were normal in all. Routine clinical laboratory tests are insensitive for the detection of early renal effects of heavy metal exposure. Measurements of renal tubular reabsorptive capacity for glucose appears to be a sensitive method for the early detection of renal effect of lead.

  15. The Relationship Between the Adverse Events and Efficacy of Sorafenib in Patients With Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Study from Northwest China.

    PubMed

    Zheng, Yu; Wang, Fuli; Wu, Guojun; Zhang, Longlong; Wang, Yangmin; Wang, Zhiping; Chen, Peng; Wang, Qing; Lu, Jingyi; Wang, Yujie; Li, Peijun; Wang, Jian; Lu, Xitao; Yuan, Jianlin

    2015-12-01

    The aim of the study is to evaluate the relationship between the adverse events and efficacy of sorafenib in patients with metastatic renal cell carcinoma (mRCC), with a purpose to guide the judgment of efficacy in sorafenib treatment.Eighty-three mRCC patients who received sorafenib therapy at northwest China were studied retrospectively. Univariate and multivariate analyses were performed to correlate tumor response, progression-free survival (PFS), and overall survival (OS) with adverse event types and grades.Among 83 patients who underwent sorafenib therapy, 2 cases (2.4%) had completed response (CR), 14 cases (16.9%) had partial response (PR), 57 cases (68.7%) had stable disease (SD), and 10 cases (12.0%) developed progressive disease (PD). The median PFS and OS were 15.0 and 29.0 months, respectively. The most frequent grade 1 or 2 adverse events included hand-foot syndrome (68.7%), diarrhea (54.2%), and alopecia (51.8%). The most common grade 3 or 4 adverse events were hand-foot syndrome (6.0%), hypertension (4.8%), and diarrhea (3.6%). The frequency and severity of adverse events correlated with tumor response rate (both with P < 0.05). Multivariate analysis showed the independent predictors of better PFS included rash (OR 0.307, 95%CI 0.148-0.636, P = 0.001) and diarrhea (OR 0.391, 95%CI 0.169-0.783, P = 0.008). Elevated transaminase was the independent predictor of poor PFS (OR 2.606, 95%CI 1.299-5.532, P = 0.012). For OS, rash (OR 0.473, 95%CI 0.253-0.886, P = 0.019) and diarrhea (OR 0.321, 95%CI 0.171-0.605, P = 0.000) correlated with better OS.Sorafenib-related adverse events are associated with efficacy in patients with mRCC from northwest China. Rash and diarrhea are independent protective factors of both PFS and OS, and elevated transaminase is an independent risk factor of PFS. A large prospective study is warranted.

  16. Effect of thyroid hormone status and concomitant medication on statin induced adverse effects in hyperlipidemic patients.

    PubMed

    Berta, E; Harangi, M; Zsíros, N; Nagy, E V; Paragh, G; Bodor, M

    2014-06-01

    Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP

  17. Effect of 2'-phosphophloretin on renal function in chronic renal failure rats.

    PubMed

    Peerce, B E; Weaver, L; Clarke, R D

    2004-07-01

    Hyperhosphatemia and secondary hyperparathyroidism are common and severe complications of chronic renal failure. Therapies to reduce serum phosphate have been shown to reduce serum parathyroid hormone (PTH) and slow the progression of renal failure. The effect of the inhibitor of intestinal phosphate absorption, 2'-phosphophloretin (2'-PP), on serum and urine chemistry, renal histology, and cardiac structure in the uremic rat model of renal failure, 5/6 nephrectomy (5/6 NX), was examined. The effect of 2'-PP on serum phosphate, serum PTH, serum total Ca(2+), and ionized Ca(2+), Ca(2+) x P(i) product, urine protein, urine osmolality, and creatinine clearance in 5/6 NX rats was examined. Uremic rats in chronic renal failure were gavaged daily with 25 microM 2'-PP. Over the course of a 5-wk experiment, serum chemistry in untreated uremic rats, 2'-PP-treated uremic rats, and age-matched control rats with normal renal function was determined twice a week. Urine creatinine, urine osmolality, urine phosphate, and urine protein were determined once a week from 24-h collections. 2'-PP reduced serum phosphate 40 +/- 3% compared with a 17% increase in untreated uremic control rats. 2'-PP did not alter total serum Ca(2+). During 5-wk experiments, serum PTH increased 65 +/- 25% in untreated uremic rats and decreased 70 +/- 7% in uremic rats treated with 25 microM 2'-PP. Creatinine clearance decreased 20% in untreated uremic rats compared with a 100% increase in 2'-PP-treated uremic rats. Urine protein decreased and urine osmolality increased in uremic rats treated with 2'-PP. The mechanism of the effect of 2'-PP on serum phosphate was inhibition of intestinal phosphate absorption. 2-PP inhibited intestinal phosphate absorption 50% without altering dietary protein absorption or intestinal Ca(2+) absorption. Over the course of the 5-wk treatment with 2'-PP, uremic animals treated with 2'-PP had a 2-4% weight gain/wk, similar to the weight gain seen in age-matched control rats

  18. Endocrine and Metabolic Adverse Effects of Psychotropic Medications in Children and Adolescents

    ERIC Educational Resources Information Center

    Correll, Christoph U.; Carlson, Harold E.

    2006-01-01

    Objective: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. Method: Selective review of endocrine and metabolic effects of psychotropic…

  19. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.; Discala, V. A.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero g or space, in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast 5 of the 7 remaining rats increased the fraction of the filtered sodium excreted (C sub Na/GFR, p .05) and their urinary flow rate (V, p .05). Potassium excretion increased (U sub k V, p .05). End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause, in rats, a decrease in distal tubular sodium, water and potassium reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis.

  20. Effects of chronic and acute protein administration on renal function in patients with chronic renal insufficiency.

    PubMed

    Bilo, H J; Schaap, G H; Blaak, E; Gans, R O; Oe, P L; Donker, A J

    1989-01-01

    In 6 volunteers with normal renal function, we investigated the effects of various kinds of protein (soy, lactoprotein and beef) and various amounts of an intravenously administered amino acid solution on glomerular filtration (GFR) and effective renal plasma flow (ERPF). As for the protein-induced changes in renal function, rises in GFR and ERPF were lowest with soy protein, and highest with beef (baseline GFR, 110 +/- 5; soy, 122 +/- 5; beef, 131 +/- 5 ml/min/1.73 m2; mean +/- SEM). High doses of intravenous amino acids induced a rise in GFR comparable to that after beef (132 +/- 5 ml/min/1.73 m2). In a combined test a liquid mixed meal together with intravenously administered amino acids induced a comparable increase of the GFR (baseline 114 +/- 5 versus 129 +/- 5 ml/min/1.73 m2). When investigating 9 patients with chronic renal insufficiency after 4 weeks of low protein intake (LP) and after 4 weeks of high protein intake (HP), GFR and ERPF rose significantly under baseline conditions (GFR-LP41 +/- 9 versus GFR-HP 45 +/- 9 ml/min/1.73 m2, p less than 0.02; ERPF-LP 169 +/- 39 versus ERPF-HP 180 +/- 40 ml/min/1.73 m2, p less than 0.02; paired Wilcoxon). At the end of both dietary periods a comparable rise in renal function could be induced through acute stimulation (GFR-LP 20 +/- 5, GFR-HP 16 +/- 4; ERPF-LP 23 +/- 7, ERPF-HP 22 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)

  1. The lifelong effects of early childhood adversity and toxic stress.

    PubMed

    Boyce, W Thomas

    2014-01-01

    A rapidly expanding body of research indicates that early social environments characterized by adversity, subordination and stress, along with individual differences in susceptibility to such environments, create risks for lifelong chronic diseases, including declines in oral health. Emerging findings suggest that gene-environment interplay, resulting in epigenetically regulated differences in gene expression, underlie many such declines in health. The origins of these processes in early life reveal how many of the chronic morbidities of adulthood should be viewed as developmental disorders, with etiologic roots in childhood.

  2. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  3. 40 CFR 152.125 - Submission of information pertaining to adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... to adverse effects. 152.125 Section 152.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Obligations and Rights of Registrants § 152.125 Submission of information pertaining to adverse effects. If at any time the...

  4. 40 CFR 152.125 - Submission of information pertaining to adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... to adverse effects. 152.125 Section 152.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Obligations and Rights of Registrants § 152.125 Submission of information pertaining to adverse effects. If at any time the...

  5. 40 CFR 152.125 - Submission of information pertaining to adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... to adverse effects. 152.125 Section 152.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Obligations and Rights of Registrants § 152.125 Submission of information pertaining to adverse effects. If at any time the...

  6. 40 CFR 152.125 - Submission of information pertaining to adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... to adverse effects. 152.125 Section 152.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Obligations and Rights of Registrants § 152.125 Submission of information pertaining to adverse effects. If at any time the...

  7. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  8. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  9. 40 CFR 152.125 - Submission of information pertaining to adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... to adverse effects. 152.125 Section 152.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Obligations and Rights of Registrants § 152.125 Submission of information pertaining to adverse effects. If at any time the...

  10. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  11. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  12. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  13. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  14. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  15. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  16. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  17. [Hypophosphatemia and refeeding syndrome: a severe and underdiagnosed adverse effect].

    PubMed

    Monti, M; Lamy, O

    2003-10-08

    A 68-year-old woman was hospitalised because of generalised weakness and development of confusional state, related to severe hyponatremia, probably due to an eating disorder with malnutrition. During the first days of hospitalisation the patient eats surprising large amounts of food. The worsening of the confusional state in spite of normalisation of natremia, and the progressive development of anemia and thrombocytopenia, leads to the discovery of a new onset severe hypophosphatemia. The rapid fall in plasma levels of phosphorus, magnesium and potassium are the main futures of the refeeding syndrome. Its clinical manifestations are neurological, muscular, haematological and renal. The development of this syndrome is associated with a high mortality. The refeeding syndrome is seen when carbohydrates are introduced after a period of malnutrition. Identification of patients at risk for the refeeding syndrome (anorexia nervosa, chronic alcoholism, chronic malnutrition, elderly patients, oncology patients), the introduction of cautious progressive nutrition and the careful monitoring of vital signs, electrolytes levels and fluid balance, allows to prevent morbidity and mortality of this syndrome.

  18. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment.

    PubMed

    Kiff, Cara J; Cortes, Rebecca; Lengua, Lilana; Kosterman, Rick; Hawkins, J David; Mason, W Alex

    2012-06-01

    Effects of Timing of Adversity on Adolescent and Young Adult Adjustment Abstract Exposure to adversity during childhood and adolescence predicts adjustment across development. Further, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal sample (N = 808) was followed from age 10 through 27. Perceptions of neighborhood in childhood predicted depression, alcohol use disorders, and HIV risk in young adulthood. Further, the timing of adversity was important in determining the type of problem experienced in adulthood. Youth adjustment predicted adult outcomes, and in some cases, mediated the relation between adversity and outcomes. These findings support the importance of adversity in predicting adjustment and elucidate factors that affect outcomes into young adulthood.

  19. Renal dysfunction after total body irradiation: Dose-effect relationship

    SciTech Connect

    Kal, Henk B. . E-mail: H.B.Kal@UMCUtrecht.nl; Kempen-Harteveld, M. Loes van

    2006-07-15

    Purpose: Late complications related to total body irradiation (TBI) as part of the conditioning regimen for hematopoietic stem cell transplantation have been increasingly noted. We reviewed and compared the results of treatments with various TBI regimens and tried to derive a dose-effect relationship for the endpoint of late renal dysfunction. The aim was to find the tolerance dose for the kidney when TBI is performed. Methods and Materials: A literature search was performed using PubMed for articles reporting late renal dysfunction. For intercomparison, the various TBI regimens were normalized using the linear-quadratic model, and biologically effective doses (BEDs) were calculated. Results: Eleven reports were found describing the frequency of renal dysfunction after TBI. The frequency of renal dysfunction as a function of the BED was obtained. For BED >16 Gy an increase in the frequency of dysfunction was observed. Conclusions: The tolerance BED for kidney tissue undergoing TBI is about 16 Gy. This BED can be realized with highly fractionated TBI (e.g., 6 x 1.7 Gy or 9 x 1.2 Gy at dose rates >5 cGy/min). To prevent late renal dysfunction, the TBI regimens with BED values >16 Gy (almost all found in published reports) should be applied with appropriate shielding of the kidneys.

  20. Impact of pregnancy on underlying renal disease.

    PubMed

    Baylis, Chris

    2003-01-01

    Normal pregnancy involves marked renal vasodilation and large increases in glomerular filtration rate (GFR). Studies in rats reveal that the gestational renal vasodilation is achieved by parallel reductions in tone in afferent and efferent arterioles so GFR rises without a change in glomerular blood pressure. There is some evidence from animal studies that increased renal generation of nitric oxide (NO) may be involved. Although chronic renal vasodilation has been implicated in causing progression of renal disease in nonpregnant states by glomerular hypertension, there are no long-term deleterious effects of pregnancies on the kidney when maternal renal function is normal because glomerular blood pressure remains normal. When maternal renal function is compromised before conception, there are no long-term adverse effects on renal function in most types of renal disease, providing that the GFR is well maintained before conception. When serum creatinine exceeds approximately 1.4 mg/dL, pregnancy may accelerate the renal disease increases and when serum creatinine >2 mg/dL, the chances are greater than 1 in 3 that pregnancy will hasten the progression of the renal disease. The available animal studies suggest that glomerular hypertension does not occur despite diverse injuries. Thus, the mechanisms of the adverse interaction between pregnancy and underlying renal disease remain unknown.

  1. The Effects of Heart Failure on Renal Function

    PubMed Central

    Udani, Suneel M; Koyner, Jay L

    2010-01-01

    Summary Heart-kidney interactions have been increasingly recognized by clinicians and researchers involved in the study and treatment of heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Recent work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of the concomitant cardiac and renal dysfunction remains unclear; however, increasing evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. PMID:20621250

  2. Transient Adverse Side Effects During Neurofeedback Training: A Randomized, Sham-Controlled, Double Blind Study.

    PubMed

    Rogel, Ainat; Guez, Jonathan; Getter, Nir; Keha, Eldad; Cohen, Tzlil; Amor, Tali; Todder, Doron

    2015-09-01

    The benefits of clinical neurofeedback training are well known, however, its adverse side-effects are less studied. This research focuses on the transient adverse side effects of neurofeedback training via a double-blind, sham/controlled methodology. Thirty healthy undergraduate students volunteers were randomly divided into three treatment groups: increasing a modified Sensory Motor Rhythm, increasing Upper Alpha, and Sham/control group who receive a random reward. The training sessions were administered for a total of ten sessions. Questionnaires of transient adverse side effects were completed by all volunteers before each session. The results suggest that similar to most medical treatments, neurofeedback can cause transient adverse side effects. Moreover, most participants reported experiencing some side effects. The side effects can be divided into non-specific side effect, associated with the neurofeedback training in general and specific ones associated with the particular protocol. Sensory Motor Rhythm protocol seems to be the most sensitive to side effects.

  3. Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

    EPA Science Inventory

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe res...

  4. Separate and Cumulative Effects of Adverse Childhood Experiences in Predicting Adult Health and Health Care Utilization

    ERIC Educational Resources Information Center

    Chartier, Mariette J.; Walker, John R.; Naimark, Barbara

    2010-01-01

    Objectives: Objectives of this population-based study were: (1) to examine the relative contribution of childhood abuse and other adverse childhood experiences to poor adult health and increased health care utilization and (2) to examine the cumulative effects of adverse childhood experiences on adult health and health care utilization. Methods:…

  5. Effect of Two Different Methods of Initiating Atomoxetine on the Adverse Event Profile of Atomoxetine

    ERIC Educational Resources Information Center

    Greenhill, Laurence L.; Newcorn, Jeffrey H.; Gao, Haitao; Feldman, Peter D.

    2007-01-01

    Objective: To compare the effects of two different methods for initiating atomoxetine in terms of the incidence of early adverse events. Method: Data on atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were analyzed from five randomized, double-blind, placebo-controlled, acute-phase studies. Two studies involve…

  6. [Ibopamine--acute hemodynamic, renal and neurohumoral effects].

    PubMed

    Wehling, M; Theisen, K

    1991-01-01

    Ibopamine (IP) is a novel dopamine analogue for which beneficial effects have been shown in chronic heart failure. Hemodynamic effects of the substance include an increase in cardiac output and a decrease in the peripheral resistance. Aside from these hemodynamic effects, changes in renal (increased diuresis) and neurohumoral parameters (decreased plasma renin activity, aldosterone, norepinephrine, increased ANF and cGMP) have been found. The renal effects may originate from three independent mechanisms: 1) direct impact of improved hemodynamic parameters on the renal perfusion; 2) the improved cardiac performance results in a reduction of compensatory hormonal adaptations, such as the activation of the renin-angiotensin-aldosterone-axis or the sympathetic system; 3) direct effects on the intrarenal hemodynamic and glomerular/tubular functions induced by stimulation of renal dopaminergic receptors. The continued decrease of the plasma renin activity by 35% results in a reduction of the plasma levels of angiotensin II and aldosterone. Additionally, an increase in plasma atrial natriuretic factor (ANF) and its second messenger cyclic guanosine monophosphate (cGMP) was observed after ibopamine, which could contribute to the diuretic action of the drug. These findings underline the importance of extrarenal effects of a drug in the treatment of heart failure, this may essentially contribute to the improvement of cardiac performance, independent of positive inotropy.

  7. Activation of TREK-1 by morphine results in analgesia without adverse side effects.

    PubMed

    Devilliers, Maïly; Busserolles, Jérôme; Lolignier, Stéphane; Deval, Emmanuel; Pereira, Vanessa; Alloui, Abdelkrim; Christin, Marine; Mazet, Bruno; Delmas, Patrick; Noel, Jacques; Lazdunski, Michel; Eschalier, Alain

    2013-01-01

    Morphine is the gold-standard pain reliever for severe acute or chronic pain but it also produces adverse side effects that can alter the quality of life of patients and, in some rare cases, jeopardize the vital prognosis. Morphine elicits both therapeutic and adverse effects primarily through the same μ opioid receptor subtype, which makes it difficult to separate the two types of effects. Here we show that beneficial and deleterious effects of morphine are mediated through different signalling pathways downstream from μ opioid receptor. We demonstrate that the TREK-1 K(+) channel is a crucial contributor of morphine-induced analgesia in mice, while it is not involved in morphine-induced constipation, respiratory depression and dependence-three main adverse effects of opioid analgesic therapy. These observations suggest that direct activation of the TREK-1 K(+) channel, acting downstream from the μ opioid receptor, might have strong analgesic effects without opioid-like adverse effects.

  8. Evaluation of the therapeutic effect of percutaneous nephroureterolithotomy by Tc-99m diethylenetiaminepentaacetic acid (DTPA) renal scintigraphy--alteration of the renal fraction of blood flow, split-GFR, and renal mean transit time.

    PubMed

    Ishibashi, M; Morita, S; Rabito, C A; Umezaki, N; Matsuoka, K; Noda, S; Eto, K; Ohtake, H

    1990-01-01

    To evaluate the therapeutic effects of percutaneous nephroureterolithotomy, the renal function of eleven patients with renal calculi was studied, pre- and post-intervention. Renal function was determined, by renal scintigraphy with the renal agent, Tc-99m diethylenetriaminepentaacetic acid (DTPA). In each renal scintigram the renogram curve was analyzed and the following were determined by deconvolution analysis; the renal fraction of blood flow (RFBF), DTPA-glomerular filtration ratio (GFR), and the renal mean transit time (MTT). The successful results in percutaneous nephroureterolithotomy (PNL) was proven using the radionuclide technique in most cases. From these results it can be concluded that renal scintigraphy is an effective procedure to evaluate the effect of PNL for treating renal calculi and secondary hydronephrosis.

  9. Effectiveness of Micro-Blowing Technique in Adverse Pressure Gradients

    NASA Technical Reports Server (NTRS)

    Welch, Gerard E.; Larosiliere, Louis M.; Hwang, Danny P.; Wood, Jerry R.

    2001-01-01

    The impact of the micro-blowing technique (MBT) on the skin friction and total drag of a strut in a turbulent, strong adverse-pressure-gradient flow is assessed experimentally over a range of subsonic Mach numbers (0.3 less than M less than 0.7) and reduced blowing fractions (0 less than or equal to 2F/C (sub f,o) less than or equal to 1.75). The MBT-treated strut is situated along the centerline of a symmetric 2-D diffuser with a static pressure rise coefficient of 0.6. In agreement with presented theory and earlier experiments in zero-pressure-gradient flows, the effusion of blowing air reduces skin friction significantly (e.g., by 60% at reduced blowing fractions near 1.75). The total drag of the treated strut with blowing is significantly lower than that of the treated strut in the limit of zero-blowing; further, the total drag is reduced below that of the baseline (solid-plate) strut, provided that the reduced blowing fractions are sufficiently high. The micro-blowing air is, however, deficient in streamwise momentum and the blowing leads to increased boundary-layer and wake thicknesses and shape factors. Diffuser performance metrics and wake surveys are used to discuss the impact of various levels of micro-blowing on the aerodynamic blockage and loss.

  10. Effects of microgravity on renal stone risk assessment

    NASA Technical Reports Server (NTRS)

    Pietrzyk, R. A.; Pak, C. Y. C.; Cintron, N. M.; Whitson, P. A.

    1992-01-01

    Physiologic changes induced during human exposure to the microgravity environment of space may contribute to an increased potential for renal stone formation. Renal stone risk factors obtained 10 days before flight and immediately after return to earth indicated that calcium oxalate and uric acid stone-forming potential was increased after space flights of 4-10 days. These data describe the need for examining renal stone risk during in-flight phases of space missions. Because of limited availability of space and refrigerated storage on spacecraft, effective methods must be developed for collecting urine samples in-flight and for preserving (or storing) them at temperatures and under conditions commensurate with mission constraints.

  11. [Renal side effects of long-term lithium therapy].

    PubMed

    Ibbeken, C; Becker, J U; Baumgärtel, M W

    2012-01-01

    Lithium is widely used in the treatment of bipolar disorders. Long-term administration of lithium often leads to side effects concerning the subjects: nephrology, endocrinology and surgery. This review emphasizes nephrotoxicity.Lithium treatment may disturb responsiveness to antidiuretic hormone (ADH), causing a nephrogenic diabetes insipidus. Furthermore long-term lithium therapy may trigger hyperparathyreoidism with hypercalcemia and chronic interstitial nephritis with development of microcysts. Long-term patients have an increased risk to develop impaired renal function. Lithium-induced endstage renal disease is rare. Termination of lithium treatment may decrease the risk of progression.To ensure security of lithium treatment regular controls of urine osmolarity, lithium-, creatinine- , thyroid stimulating hormone- and calcium-levels are essential. Patients with decreased renal function should be referred to a specialist early.

  12. Beneficial effects of soy protein consumption for renal function.

    PubMed

    Anderson, James W

    2008-01-01

    Alterations in dietary protein intake have an important role in prevention and management of several forms of kidney disease. Using soy protein instead of animal protein reduces development of kidney disease in animals. Reducing protein intake preserves kidney function in persons with early diabetic kidney disease. Our clinical observations led us to the soy-protein hypothesis that "substitution of soy protein for animal protein results in less hyperfiltration and glomerular hypertension with resulting protection from diabetic nephropathy." These components of soy protein may lead to the benefits: specific peptides, amino acids, and isoflavones. Substituting soy protein for animal protein usually decreases hyperfiltration in diabetic subjects and may reduce urine albumin excretion. Limited data are available on effects of soy peptides, isoflavones, and other soy components on renal function on renal function in diabetes. Further studies are required to discern the specific benefits of soy protein and its components on renal function in diabetic subjects.

  13. Effects of water immersion on renal hemodynamics in normal man

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Levinson, R.; Loutzenhiser, R.

    1976-01-01

    The present study was undertaken to delineate the effects of water immersion to the neck (NI) on renal plasma flow and glomerular filtration rate as assessed by the clearance of p-aminohippuric acid (PAH) and inulin, respectively. Nine normal male subjects were studied on two occasions, control and NI. The conditions of seated posture and time of day were identical. Immersion did not alter either clearance at a time when sodium excretion was increasing markedly. The constancy of PAH clearance during NI suggests that renal blood flow is unaltered and that the natriuresis of NI is mediated independently of alterations in overall renal perfusion. The sluggish decline of a natriuresis during recovery is consistent with the presence of a humoral factor contributing to the encountered natriuresis.

  14. Adverse effects of extra-articular corticosteroid injections: a systematic review

    PubMed Central

    2010-01-01

    Background To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue) corticosteroid injection. Methods A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case reports were included, as were prospective and retrospective studies that reported adverse events of corticosteroid injection. All clinical trials which used extra-articular corticosteroid injections were examined. We divided the reported adverse events into major (defined as those needing intervention or not disappearing) and minor ones (transient, not requiring intervention). Results The search yielded 87 relevant studies:44 case reports, 37 prospective studies and 6 retrospective studies. The major adverse events included osteomyelitis and protothecosis; one fatal necrotizing fasciitis; cellulitis and ecchymosis; tendon ruptures; atrophy of the plantar fat was described after injecting a neuroma; and local skin effects appeared as atrophy, hypopigmentation or as skin defect. The minor adverse events effects ranged from skin rash to flushing and disturbed menstrual pattern. Increased pain or steroid flare after injection was reported in 19 studies. After extra-articular injection, the incidence of major adverse events ranged from 0-5.8% and that of minor adverse events from 0-81%. It was not feasible to pool the risk for adverse effects due to heterogeneity of study populations and difference in interventions and variance in reporting. Conclusion In this literature review it was difficult to accurately quantify the incidence of adverse effects after extra-articular corticosteroid injection. The reported adverse events were relatively mild, although one fatal reaction was reported. PMID:20836867

  15. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis

    PubMed Central

    Trindade, E; Menon, D; Topfer, L A; Coloma, C

    1998-01-01

    BACKGROUND: The use of antidepressant medications and the resulting costs have increased dramatically in recent years, partly because of the introduction of selective serotonin reuptake inhibitors (SSRIs). An assessment of the clinical and economic aspects of SSRIs compared with the older tricyclic antidepressants (TCAs) was initiated to generate information for purchasers of these drugs as well as clinicians. One component of this study was an examination of the adverse effects associated with the use of these drugs. METHODS: Searches of bibliographic databases (for January 1980 through May 1996) and manual scanning of both peer-reviewed publications and other documents were used to identify double-blind, randomized controlled trials involving at least one SSRI and one TCA. For the study of adverse effects, only trials that had at least 20 patients in each trial arm and that reported rates of adverse effects in both arms were retained. In total 84 trials reporting on 18 adverse effects were available. Meta-analyses were undertaken to calculate pooled differences in rates of adverse effects. The question of whether the method of eliciting information from patients about adverse effects made a difference in the findings was also examined. Finally, differences in drop-out rates due to adverse effects were calculated. RESULTS: The crude rates of occurrence of adverse effects ranged from 4% (palpitations) to 26% (nausea) for SSRIs and from 4% (diarrhea) to 27% (dry mouth) for TCAs. The differences in the rates of adverse effects between the 2 types of drugs ranged from 14% more with SSRIs (for nausea) to 11% more with TCAs (for constipation). The results did not depend on the method of eliciting information from patients. There were no statistically significant differences between drug classes in terms of drop-outs due to adverse effects. INTERPRETATION: SSRIs and TCAs are both associated with adverse effects, although the key effects differ between the drug classes

  16. Multidisciplinary approach to identification and remedial intervention for adverse late effects of cancer therapy

    SciTech Connect

    McCalla, J.L.

    1985-03-01

    Because of advances in surgical technique, radiation therapy, and combined chemotherapy regimens, there has been a dramatic improvement in the survival of children with pediatric malignancies. All treatment modalities are associated with adverse effects that may be manifested months to years after therapy. This article has provided an overview of the physiologic and psychologic adverse effects of antineoplastic therapy and described the multidisciplinary approach used by one institution to identify and initiate appropriate remedial intervention. Nurses can learn to assist in the identification of adverse late effects, provide support to the family, and facilitate appropriate intervention.

  17. Managing patients with side effects and adverse events to immunoglobulin therapy.

    PubMed

    Azizi, Gholamreza; Abolhassani, Hassan; Asgardoon, Mohammad Hossein; Shaghaghi, Shiva; Negahdari, Babak; Mohammadi, Javad; Rezaei, Nima; Aghamohammadi, Asghar

    2016-01-01

    Immunoglobulin therapy has not only served as a lifesaving approach for the prevention and treatment of infections in primary and secondary immunodeficiency diseases, but has also been used as an immunomodulatory agent for autoimmune and inflammatory disorders and to provide passive immunity for some infectious diseases. Most of the adverse effects associated with immunoglobulin therapy are mild, transient and self-limiting. However, serious side effects also occur. Therefore, to minimize the adverse events of immunoglobulin therapy, specialist review of patient clinical status and immunoglobulin products, in addition to selection of appropriate treatment strategy for the management of patients with associated side effects and adverse events, are crucial.

  18. The lifelong effects of early childhood adversity and toxic stress.

    PubMed

    Shonkoff, Jack P; Garner, Andrew S

    2012-01-01

    Advances in fields of inquiry as diverse as neuroscience, molecular biology, genomics, developmental psychology, epidemiology, sociology, and economics are catalyzing an important paradigm shift in our understanding of health and disease across the lifespan. This converging, multidisciplinary science of human development has profound implications for our ability to enhance the life prospects of children and to strengthen the social and economic fabric of society. Drawing on these multiple streams of investigation, this report presents an ecobiodevelopmental framework that illustrates how early experiences and environmental influences can leave a lasting signature on the genetic predispositions that affect emerging brain architecture and long-term health. The report also examines extensive evidence of the disruptive impacts of toxic stress, offering intriguing insights into causal mechanisms that link early adversity to later impairments in learning, behavior, and both physical and mental well-being. The implications of this framework for the practice of medicine, in general, and pediatrics, specifically, are potentially transformational. They suggest that many adult diseases should be viewed as developmental disorders that begin early in life and that persistent health disparities associated with poverty, discrimination, or maltreatment could be reduced by the alleviation of toxic stress in childhood. An ecobiodevelopmental framework also underscores the need for new thinking about the focus and boundaries of pediatric practice. It calls for pediatricians to serve as both front-line guardians of healthy child development and strategically positioned, community leaders to inform new science-based strategies that build strong foundations for educational achievement, economic productivity, responsible citizenship, and lifelong health.

  19. 28-day repeated dose response study of diglycolic acid: Renal and hepatic effects.

    PubMed

    Sprando, Robert L; Mossoba, Miriam E; Black, Thomas; Keltner, Zachary; Vohra, Sanah; Olejnik, Nicholas; Toomer, Howard; Stine, Cynthia; Evans, Eric; Sprando, Jessica L; Ferguson, Martine

    2017-03-25

    The acute oral toxicity of diglycolic acid (DGA) was evaluated. Groups of female rats (n = 8 rats/group) received 28 consecutive daily single doses of 0.3, 1.0, 3.0, 10.0, 30.0, 100.0 or 300.0 mg DGA/kg body weight by gastric intubation. One group of animals served as vehicle control. Tissues and blood serum were collected at necropsy on day 29. Select organs were weighed and fixed in formalin for histopathological analysis. Animals from the 300 mg/kg bw dose group were removed from the study after 5 consecutive days of treatment as a consequence of adverse treatment related effects. The animals in the remaining treatment groups survived the exposure period. No adverse clinical signs were observed throughout the exposure period in the surviving animals. No significant differences from controls were observed for feed and fluid consumption or body weight gain in the surviving animals. Lesions were observed in the kidneys, liver, stomach, intestine, thymus, spleen and bone marrow in animals from the 300 mg/kg dose group and signs of renal tubular regeneration were observed only in the 100 mg/kg dose group. These results suggest that high levels of pure DGA would need to be consumed before renal and other forms of organ toxicity are observed.

  20. Alcohol and cannabis: Comparing their adverse health effects and regulatory regimes.

    PubMed

    Hall, Wayne

    2016-11-28

    The claim that the adverse health effects of cannabis are much less serious than those of alcohol has been central to the case for cannabis legalisation. Regulators in US states that have legalised cannabis have adopted regulatory models based on alcohol. This paper critically examines the claim about adverse health effects and the wisdom of regulating cannabis like alcohol. First, it compares what we know about the adverse health effects of alcohol and cannabis. Second, it discusses the uncertainties about the long term health effects of sustained daily cannabis use. Third, it speculates about how the adverse health effects of cannabis may change after legalisation. Fourth, it questions the assumption that alcohol provides the best regulatory model for a legal cannabis market. Fifth, it outlines the major challenges in regulating cannabis under the liberal alcohol-like regulatory regimes now being introduced.

  1. The Useage of Opioids and their Adverse Effects in Gastrointestinal Practice: A Review

    PubMed Central

    Khansari, MahmoudReza; Sohrabi, MasourReza; Zamani, Farhad

    2013-01-01

    Opium is one of the oldest herbal medicines currently used as an analgesic, sedative and antidiarrheal treatment. The effects of opium are principally mediated by the μ-, κ- and δ-opioid receptors. Opioid substances consist of all natural and synthetic alkaloids that are derived from opium. Most of their effects on gastrointestinal motility and secretion result from suppression of neural activity. Inhibition of gastric emptying, increase in sphincter tone, changes in motor patterns, and blockage of peristalsis result from opioid use. Common adverse effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, dependency and tolerance, and respiratory depression. The most common adverse effect of opioid use is constipation. Although stool softeners are frequently used to decrease opioid-induced bowel dysfunction, however they are not efficacious. Possibly, the use of specific opioid receptor antagonists is a more suitable approach. Opioid antagonists, both central and peripheral, could affect gastrointestinal function and visceromotor sensitivity, which suggests an important role for endogenous opioid peptides in the control of gastrointestinal physiology. Underlying diseases or medications known to influence the central nervous system (CNS) often accelerate the opioid’s adverse effects. However, changing the opioid and/or route of administration could also decrease their adverse effects. Appropriate patient selection, patient education and discussion regarding potential adverse effects may assist physicians in maximizing the effectiveness of opioids, while reducing the number and severity of adverse effects. PMID:24829664

  2. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under...

  3. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under...

  4. The effect of activated charcoal on adenine-induced chronic renal failure in rats.

    PubMed

    Ali, Badreldin H; Alza'abi, Mohamed; Ramkumar, Aishwarya; Al-Lawati, Intisar; Waly, Mostafa I; Beegam, Sumaya; Nemmar, Abderrahim; Brand, Susanne; Schupp, Nicole

    2014-03-01

    Activated charcoal (AC) is a sorbent that has been shown to remove urinary toxins like urea and indoxyl sulfate. Here, the influence of AC on kidney function of rats with experimental chronic renal failure (CRF) is investigated. CRF was induced in rats by feeding adenine (0.75%) for four weeks. As an intervention, AC was added to the feed at concentrations of 10%, 15% or 20%. Adenine treatment impaired kidney function: it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and vanin-1. Furthermore, it raised plasma concentrations of the uremic toxins indoxyl sulfate, phosphate and uric acid. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activity, total antioxidant capacity and reduced glutathione were adversely affected. Most of these changes were significantly ameliorated by dietary administration of AC at a concentration of 20%, while effects induced by lower doses of dietary AC on adenine nephrotoxicity were not statistically significant. The results suggest that charcoal is a useful sorbent agent in dietary adenine-induced CRF in rats and that its usability as a nephroprotective agent in human kidney disease should be studied.

  5. The adverse effects profile of levetiracetam in epilepsy: a more detailed look.

    PubMed

    Mbizvo, Gashirai K; Dixon, Pete; Hutton, Jane L; Marson, Anthony G

    2014-09-01

    The adverse effects profile of levetiracetam in epilepsy is still being fully described. We recently published a Cochrane Review evaluating the effectiveness of levetiracetam, added on to usual care, in treating drug-resistant focal epilepsy. The five most common adverse effects were reported and analysed with no scope for reporting any less common adverse effects than those. Here, we report and analyse the remaining adverse effects (including the five most common). These were (in decreasing order of frequency) somnolence; headache; asthenia; accidental injury; dizziness; infection; pharyngitis; pain; rhinitis; abdominal pain; flu syndrome; vomiting; diarrhoea; convulsion; nausea; increased cough; anorexia; upper respiratory tract infection; hostility; personality disorder; urinary tract infection; nervousness; depression; aggression; back pain; agitation; emotional liability; psychomotor hyperactivity; pyrexia; rash; ECG abnormalities; decreased appetite; nasal congestion; irritability; abnormal behaviour; epistaxis; insomnia; altered mood; anxiety; bloody urine; diplopia; dissociation; memory impairment; pruritis; increased appetite; acne; and stomach discomfort. Only somnolence and infection were significantly associated with levetiracetam. When adverse effects pertaining to infection were combined, these affected 19.7% and 15.1% of participants on levetiracetam and placebo (relative risk 1.16, CI 0.89-1.50, Chi(2) heterogeneity p = 0.13). Somnolence and infection further retained significance in adults while no single adverse effect was significant in children. This review updates the adverse effects profile data on levetiracetam use by empirically reporting its common and uncommon adverse effects and analysing their relative importance statistically using data from a group of trials that possess low Risk of Bias and high Quality of Evidence GRADE scores.

  6. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  7. Chronic renal disease in pregnancy.

    PubMed

    Ramin, Susan M; Vidaeff, Alex C; Yeomans, Edward R; Gilstrap, Larry C

    2006-12-01

    The purpose of this review was to examine the impact of varying degrees of renal insufficiency on pregnancy outcome in women with chronic renal disease. Our search of the literature did not reveal any randomized clinical trials or meta-analyses. The available information is derived from opinion, reviews, retrospective series, and limited observational series. It appears that chronic renal disease in pregnancy is uncommon, occurring in 0.03-0.12% of all pregnancies from two U.S. population-based and registry studies. Maternal complications associated with chronic renal disease include preeclampsia, worsening renal function, preterm delivery, anemia, chronic hypertension, and cesarean delivery. The live birth rate in women with chronic renal disease ranges between 64% and 98% depending on the severity of renal insufficiency and presence of hypertension. Significant proteinuria may be an indicator of underlying renal insufficiency. Management of pregnant women with underlying renal disease should ideally entail a multidisciplinary approach at a tertiary center and include a maternal-fetal medicine specialist and a nephrologist. Such women should receive counseling regarding the pregnancy outcomes in association with maternal chronic renal disease and the effect of pregnancy on renal function, especially within the ensuing 5 years postpartum. These women will require frequent visits and monitoring of renal function during pregnancy. Women whose renal disease is further complicated by hypertension should be counseled regarding the increased risk of adverse outcome and need for blood pressure control. Some antihypertensives, especially angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, should be avoided during pregnancy, if possible, because of the potential for both teratogenic (hypocalvaria) and fetal effects (renal failure, oliguria, and demise).

  8. [Parkinson syndrome, a possible adverse effect of calcium inhibitors].

    PubMed

    Malaterre, H R; Lauribe, P; Paganelli, F; Ramond, B; Lévy, S

    1992-09-01

    The effects of calcium inhibitors are not limited to the muscles and may affect other systems and cause varied side effects. Two cases of Parkinsonian syndrome occurring after starting therapy with calcium inhibitors (verapamil in one case and diltiazem in the other) are reported. Complete regression of the symptoms after withdrawing the drugs was strongly in favour of a causal relationship. The condition could be due to inhibition of the calcium channels in the central nervous system disturbing neurotransmission. This seems to be a rare side effect as there have only been three other reported cases of secondary extrapyramidal syndromes in the literature. However, a Parkinsonian syndrome is very invalidating and clinicians using this family of drugs should be aware of this possible complication.

  9. Ecchymoses as an adverse effect of fluoxetine treatment.

    PubMed

    Fountoulakis, Konstantinos N; Samolis, Stavros; Iacovides, Apostolos; St Kaprinis, George

    2007-07-30

    We report a case of a 28-year-old major depressive female patient who manifested ecchymoses following fluoxetine use. After substitution of sertraline, her depression resolved after 4 weeks and ecchymoses 1.5 months latter. This is an unexplored side-effect with unknown long-term consequences that warrants further study.

  10. The (Adverse) Effects of Expanding Higher Education: Evidence from Italy

    ERIC Educational Resources Information Center

    Oppedisano, Veruska

    2011-01-01

    Over the period 1995-1998 Italy experienced an expansion of its higher education supply with the aim of reducing regional differences in educational attainment. This paper evaluates the effects of this policy on enrolment, drop out and academic performance. The paper combines differences across provinces in the number of campuses constructed with…

  11. Concrete blocks` adverse effects on indoor air and recommended solutions

    SciTech Connect

    Ruppersberger, J.S.

    1995-04-01

    Air infiltration through highly permeable concrete blocks can allow entry of various serious indoor air pollutants including radon. An easy approach to avoiding these pollutants is to select a less-air-permeable concrete block. Tests show that air permeability of concrete blocks can vary by a factor greater than 50 (0.63--35 standard L/min/m{sup 2} at 3 Pa). The surface texture of the blocks correlates well with air permeability; test results of smoother, closed-surface-texture blocks were usually less air-permeable. During construction, air infiltration can be minimized by capping walls and carefully sealing around openings for utilities or other penetrations. Structures with indoor air-quality problems due to soil-gas entry can be mitigated more effectively with less coating material if the blocks have a closed surface texture. All coatings evaluated--cementaceous block filler (which has the lowest applied cost and is more than 99.5% effective), surface bonding cement, water-based epoxy, polysulfide vinyl acrylic, and latex (three coats)--were highly effective (more than 98%) in reducing air permeability when adequately applied. Coating selection should be influenced by expected service life, considering surface condition and cost.

  12. Adverse effects in children after unintentional buprenorphine exposure.

    PubMed

    Geib, Ann-Jeannette; Babu, Kavita; Ewald, Michele Burns; Boyer, Edward W

    2006-10-01

    Buprenorphine in sublingual formulation was recently introduced to the American market for treatment of opioid dependence. We report a series of 5 toddlers with respiratory and mental-status depression after unintentional buprenorphine exposure. Despite buprenorphine's partial agonist activity and ceiling effect on respiratory depression, all children required hospital admission and either opioid-antagonist therapy or mechanical ventilation. Results of routine urine toxicology screening for opioids were negative in all cases. Confirmatory testing was sent for 1 child and returned with a positive result. The increasing use of buprenorphine as a home-based therapy for opioid addiction in the United States raises public health concerns for the pediatric population.

  13. The uses and adverse effects of beryllium on health

    PubMed Central

    Cooper, Ross G.; Harrison, Adrian P.

    2009-01-01

    Context: This review describes the health effects of beryllium exposure in the workplace and the environment. Aim: To collate information on the consequences of occupational and environmental exposure to beryllium on physiological function and well being. Materials and Methods: The criteria used in the current review for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability, and Health. Articles were classified based on acute and chronic exposure and toxicity of beryllium. Results: The proportions of utilized and nonutilized articles were tabulated. Years 2001–10 gave the greatest match (45.9%) for methodological parameters, followed by 27.71% for 1991–2000. Years 1971–80 and 1981–90 were not significantly different in the information published and available whereas years 1951–1960 showed a lack of suitable articles. Some articles were published in sources unobtainable through requests at the British Library, and some had no impact factor and were excluded. Conclusion: Beryllium has some useful but undoubtedly harmful effects on health and well-being. Measures need to be taken to prevent hazardous exposure to this element, making its biological monitoring in the workplace essential. PMID:20386622

  14. The Adverse Effects of Alcohol on Vitamin A Metabolism

    PubMed Central

    Clugston, Robin D.; Blaner, William S.

    2012-01-01

    The objective of this review is to explore the relationship between alcohol and the metabolism of the essential micronutrient, vitamin A; as well as the impact this interaction has on alcohol-induced disease in adults. Depleted hepatic vitamin A content has been reported in human alcoholics, an observation that has been confirmed in animal models of chronic alcohol consumption. Indeed, alcohol consumption has been associated with declines in hepatic levels of retinol (vitamin A), as well as retinyl ester and retinoic acid; collectively referred to as retinoids. Through the use of animal models, the complex interplay between alcohol metabolism and vitamin A homeostasis has been studied; the reviewed research supports the notion that chronic alcohol consumption precipitates a decline in hepatic retinoid levels through increased breakdown, as well as increased export to extra-hepatic tissues. While the precise biochemical mechanisms governing alcohol’s effect remain to be elucidated, its profound effect on hepatic retinoid status is irrefutable. In addition to a review of the literature related to studies on tissue retinoid levels and the metabolic interactions between alcohol and retinoids, the significance of altered hepatic retinoid metabolism in the context of alcoholic liver disease is also considered. PMID:22690322

  15. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  16. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  17. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  18. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  19. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  20. Adverse health effects of air pollutants in a nonsmoking population.

    PubMed

    Pope, C A

    1996-07-17

    Utah Valley has provided an interesting and unique opportunity to evaluate the health effects of respirable particulate air pollution (PM10). Residents of this valley are predominantly nonsmoking members of the Church of Jesus Christ of Latter-day Saints (Mormons). The area has moderately high average PM10 levels with periods of highly elevated PM10 concentrations due to local emissions being trapped in a stagnant air mass near the valley floor during low-level temperature inversion episodes. Due to a labor dispute, there was intermittent operation of the single largest pollution source, an old integrated steel mill. Levels of other common pollutants including sulfur dioxide, ozone, and acidic aerosol are relatively low. Studies specific to Utah Valley have observed that elevated PM10 concentrations are associated with: (1) decreased lung function; (2) increased incidence of respiratory symptoms; (3) increased school absenteeism; (4) increased respiratory hospital admissions; and (5) increased mortality, especially respiratory and cardiovascular mortality.

  1. Real-world use of pomalidomide and dexamethasone in double refractory multiple myeloma suggests benefit in renal impairment and adverse genetics: a multi-centre UK experience.

    PubMed

    Maciocia, Nicola; Melville, Andrew; Cheesman, Simon; Sharpley, Faye; Ramasamy, Karthik; Streetly, Matthew; Jenner, Matthew; Benjamin, Reuben; Schey, Steve; Maciocia, Paul; Popat, Rakesh; D'sa, Shirley; Rismani, Ali; Cerner, Aviva; Yong, Kwee; Rabin, Neil

    2017-03-01

    Myeloma patients who become refractory to immunomodulatory agents (IMiDs) and bortezomib have poor survival, with limited therapeutic options. Pomalidomide has shown improved survival and good tolerability in this patient cohort in clinical trials, but real world data are scarce. We retrospectively analysed all patients treated with pomalidomide at five UK centres between 2013 and 2016. Of 85 patients identified, 70 had sufficient information for response assessments. Median age was 66 years [40-89], 96·5% were refractory to IMiDs, 72·9% were refractory to both an IMiD and bortezomib and 92·9% were refractory to their last treatment. Of 45 patients with fluorescence in situ hybridization results 64% had adverse risk, 19 patients (22·4%) had an estimated glomerular filtration rate <45 ml/min. Grade ≥3 non-haematological toxicities occurred in 42·4%, and grade ≥3 neutropenia and thrombocytopenia in 38% and 24% respectively, but only 18·8% had dose reductions. The overall response rate was 52·9%. At a median follow-up of 13·2 months, median progression-free survival was 5·2 months [95% confidence interval (CI) 4·150-6·238], and median overall survival was 13·7 months (95% CI 11·775-15·707). No significant difference was seen in response, survival or tolerability by renal function, age or cytogenetic risk. This real-world data support the results seen in published clinical trials.

  2. Adversity in Preschool-Aged Children: Effects on Salivary Interleukin-1β

    PubMed Central

    Tyrka, Audrey R.; Parade, Stephanie H.; Valentine, Thomas R.; Eslinger, Nicole M.; Seifer, Ronald

    2016-01-01

    Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary IL-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records, and contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. Number of past month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Post-challenge IL-1β displayed positive associations with each adversity variable, but were not significant. CRP was not significantly associated with any of the adversity variables. Given evidence suggesting involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

  3. Common Adverse Effects of Anti-TNF Agents on Gestation

    PubMed Central

    Antsaklis, Panagiotis; Galanopoulos, Nikolaos; Kontomanolis, Emmanuel

    2016-01-01

    Autoimmune disease has affected up to 50 million Americans, according to the American Autoimmune Related Diseases Association (AARDA) and 75 percent of those affected are women. These inflammatory diseases have variable activity and a lot of women will have to undergo major therapies during and after pregnancy. Many of the women suffering from these disease will improve during gestation. However a lot of women will require continuation of disease-modifying therapies (i.e., biological therapies) throughout pregnancy and post-partum involving many risks. In the past decade all gaze turned to biological therapies, as an attempt, to obtain even more effective medications in order to suppress the exacerbation of autoimmune disease, even at the most unfit circumstances such as pregnancy. The results are both satisfying and promising since increasingly proven thoughts prevail on making anti-TNF agents first-line medications, clearing up the limited knowledge over human influence. The purpose of this review is to summarize the results of the reports with the highest and representative range of patients of the last decade involving the use of anti-TNF agents during pregnancy. PMID:28044081

  4. Long-term antidepressant use: patient perspectives of benefits and adverse effects

    PubMed Central

    Cartwright, Claire; Gibson, Kerry; Read, John; Cowan, Ondria; Dehar, Tamsin

    2016-01-01

    Long-term antidepressant treatment has increased and there is evidence of adverse effects; however, little is known about patients’ experiences and views of this form of treatment. This study used mixed methods to examine patients’ views and experiences of long-term antidepressant treatment, including benefits and concerns. Data from 180 patients, who were long-term users of antidepressants (3–15 years), were extracted from an anonymous online survey of patients’ experiences of antidepressants in New Zealand. Participants had completed rating scales about the effectiveness of antidepressants, levels of depression before and during antidepressant use, quality of life, and perceived adverse effects. Two open-ended questions allowed participants to comment on personal experiences. The majority (89.4%) reported that antidepressants had improved their depression although 30% reported moderate-to-severe depression on antidepressants. Common adverse effects included withdrawal effects (73.5%), sexual problems (71.8%), and weight gain (65.3%). Adverse emotional effects, such as feeling emotionally numb (64.5%) and addicted (43%), were also common. While the majority of patients were pleased with the benefits of antidepressant treatment, many were concerned about these adverse effects. Some expressed a need for more information about long-term risks and increased information and support to discontinue. PMID:27528803

  5. Adverse effects of psychological therapy: An exploratory study of practitioners' experiences from child and adolescent psychiatry.

    PubMed

    Jonsson, Ulf; Johanson, Josefin; Nilsson, Elin; Lindblad, Frank

    2016-07-01

    The scientific knowledge about adverse effects of psychological therapies and how such effects should be detected is limited. It is possible that children and adolescents are particularly vulnerable and need specific support in order to express adverse effects. In this exploratory study, we used a qualitative approach to explore practitioners' experiences of this phenomenon. Fourteen practitioners providing psychological therapy within the Child and Adolescent Psychiatric Service were interviewed. Qualitative content analysis was applied to the data. Four overarching categories brought up by the practitioners were identified: vagueness of the concept (reflecting that the concept was novel and hard to define), psychotherapist-client interaction (encompassing aspects of the interaction possibly related to adverse effects), consequences for the young person (including a range of emotional, behavioural and social consequences) and family effects (e.g. professional complications and decreased autonomy for the parent). Professional discussions on these issues could improve psychological therapy for children and adolescents. Based on our findings and previous research, we propose three basic aspects to consider when adverse effects are detected and managed in this context: typology (form, severity and duration), aetiology (hypothesis about the causes) and perspective (adverse effects seen from the points of view of different interested parties).

  6. Assessment of Aerobic Exercise Adverse Effects during COPD Exacerbation Hospitalization

    PubMed Central

    Mesquita, Carolina Bonfanti; Caram, Laura M. O.; Dourado, Victor Zuniga; de Godoy, Irma; Tanni, Suzana Erico

    2017-01-01

    Introduction. Aerobic exercise performed after hospital discharge for exacerbated COPD patients is already recommended to improve respiratory and skeletal muscle strength, increase tolerance to activity, and reduce the sensation of dyspnea. Previous studies have shown that anaerobic activity can clinically benefit patients hospitalized with exacerbated COPD. However, there is little information on the feasibility and safety of aerobic physical activity performed by patients with exacerbated COPD during hospitalization. Objective. To evaluate the effects of aerobic exercise on vital signs in hospitalized patients with exacerbated COPD. Patients and Methods. Eleven COPD patients (63% female, FEV1: 34.2 ± 13.9% and age: 65 ± 11 years) agreed to participate. Aerobic exercise was initiated 72 hours after admission on a treadmill; speed was obtained from the distance covered in a 6-minute walk test (6MWT). Vital signs were assessed before and after exercise. Results. During the activity systolic blood pressure increased from 125.2 ± 13.6 to 135.8 ± 15.0 mmHg (p = 0.004) and respiratory rate from 20.9 ± 4.4 to 24.2 ± 4.5 rpm (p = 0.008) and pulse oximetry (SpO2) decreased from 93.8 ± 2.3 to 88.5 ± 5.7% (p < 0.001). Aerobic activity was considered intense, heart rate ranged from 99.2 ± 11.5 to 119.1 ± 11.1 bpm at the end of exercise (p = 0.092), and patients reached on average 76% of maximum heart rate. Conclusion. Aerobic exercise conducted after 72 hours of hospitalization in patients with exacerbated COPD appears to be safe. PMID:28265180

  7. Interactive effects of social adversity and respiratory sinus arrhythmia activity on reactive and proactive aggression.

    PubMed

    Zhang, Wei; Gao, Yu

    2015-10-01

    Abnormal parasympathetic nervous system (PNS)-related cardiac activity has been linked to aggression. However, little is known about how it interacts with psychosocial adversity in predisposing to reactive-proactive aggression. In the current study, 84 male and female college students self-reported reactive and proactive aggression, and were assessed for respiratory sinus arrhythmia (RSA), a measure of PNS-related cardiac activity, during rest and when they contemplated an emotion-evoking decision-making task. Regression analyses showed that (a) resting RSA was positively linked to reactive aggression in conditions of high social adversity, and (b) RSA reactivity was positively associated with reactive but negatively associated with proactive aggression, in conditions of low social adversity. Main effects were not found for psychophysiological functioning or psychosocial adversity, suggesting the importance of their interaction. Findings support a biosocial basis for aggression and add additional support for the distinctions between reactive and proactive aggression.

  8. Pretreatment Predictors of Adverse Radiation Effects After Radiosurgery for Arteriovenous Malformation

    SciTech Connect

    Hayhurst, Caroline; Monsalves, Eric; Prooijen, Monique van; Cusimano, Michael; Tsao, May; Menard, Cynthia; Kulkarni, Abhaya V.; Schwartz, Michael; Zadeh, Gelareh

    2012-02-01

    Purpose: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. Methods and Materials: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzed to identify predictors of adverse radiation effects. Results: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm{sup 3}, above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Conclusions: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series suggest the

  9. Luteinizing hormone--releasing hormone agonists: a quick reference for prevalence rates of potential adverse effects.

    PubMed

    Walker, Lauren M; Tran, Susan; Robinson, John W

    2013-12-01

    Men with prostate cancer (PCa) frequently undergo androgen deprivation therapy (ADT), typically in the form of a depot injection of luteinizing hormone-releasing hormone agonists (LHRHa). LHRHa are associated with many adverse effects (eg, hot flashes, sexual dysfunction, loss of muscle mass, osteopenia, metabolic syndrome), which drastically impact patient quality of life. This literature review, which includes a comprehensive table documenting prevalence rates, provides a quick reference for health care professionals involved in the care of men undergoing ADT with LHRHa. Primary sources were acquired from PubMed using the search terms "androgen deprivation therapy" and each potentially adverse effect (eg, "androgen deprivation therapy and hot flashes"). Commonly cited review articles were also examined for citations of original studies containing prevalence rates. More than 270 articles were reviewed. In contrast to many existing reviews, rates are cited exclusively from original sources. The prevalence rates, obtained from original sources, suggest that more than half of documented adverse effects are experienced by as many as 40% or more of patients. A critique of the literature is also provided. Although there is a vast literature of both original and review articles on specific adverse effects of LHRHa, the quality of research on prevalence rates for some adverse effects is subpar. Many review articles contain inaccuracies and do not cite original sources. The table of prevalence rates will serve as a quick reference for health care providers when counseling patients and will aid in the development of evidence-based patient education materials.

  10. Uncommon side effect of MMF in renal transplant recipients.

    PubMed

    Balal, M; Demir, E; Paydas, Saime; Sertdemir, Y; Erken, U

    2005-01-01

    Mycophenolate mofetil (MMF) is a potent immunosuppressive agent used in renal transplantation. Gastrointestinal and hematological side effects are commonly observed, but hepatotoxicity has not been reported. In this study, we assessed MMF-related hepatotoxicity in renal transplant recipients. A total of 124 renal transplantation recipients (RTRs) were evaluated for elevated liver enzymes associated with MMF, and 79 patients were enrolled to the study. Patients used MMF 2 g/day. The patients who had progressive increase in liver enzymes after renal transplantation and their AST, ALT, GGT, ALP, bilirubin levels, hepatitis, cytomegalovirus (CMV), abdominal ultrasonography, duration of hepatotoxicity, and decreased dosage or withdrawal of MMF were recorded. Also, we evaluated their liver enzymes while the patients were on the waiting list. Of the 79 patients, 11 patients (13.9%) had a progressive increase in liver enzymes. The median (min-max) age of the patients with MMF-hepatotoxicity was 29 (19-54) and 72.7% of them were male. None of the patients had hepatitis B or C, CMV infection, or other possible causes for elevated liver enzymes and their abdominal ultrasonography were normal. High liver enzyme levels regressed after the withdrawal (n=6) or reduce dosage (n=5) of MMF. The median time of the increase in liver enzymes was 28 (4-70) days and after 50% reduction or withdrawal of MMF, returned to normal values in 16 (4-210) days. The median levels of ALT in waiting list (I), before (II), and after (III) reduction dosage or withdrawal of MMF were 22.0 (3-22), 222.0 (51-508), and 33.0 (21-64) U/L, respectively (p I-II=0.004,p I-II=0.013, andp II-III=0.005). There were no differences for ALP, GGT, total bilirubin, and direct bilirubin levels. Also, the correlation between recovery time of ALT and persistence time of ALT elevation before adjustment of MMF was significant (r=0.739, p=0.009). Consequently, after renal transplantation, hepatotoxicity can occur due to a

  11. Renal effects of atriopeptin (AP) II in conscious SHR

    SciTech Connect

    Smits, J.F.; Debets, J.M.; Struyker-Boudier, H.A.; Daemen, M.J.

    1986-03-05

    Diuresis and natriuresis following APs has been suggested to depend upon increased renal blood flow (RBF). In a previous study, they found that APII infusions in conscious SHR decrease RBF. In this study, they report effects of APII on glomerular filtration rate (GFR) and renal excretory function in conscious SHR. Male SHR were equipped with arterial and venous catheters. Furthermore, a special catheter was implanted into the bladder to allow continuous urine sampling from conscious, freely moving rats. Animals were allowed at least 4 days to recover. In one group of SHR, APII (N=7) or saline (N=7) was infused to quantitate excretion of water, Na/sup +/, and K/sup +/. Two other groups of SHR (N=8 each) were infused with /sup 51/Cr-EDTA and /sup 125/I-PAH. GFR and renal plasma flow (ERPF) were calculated from urine and a mid-time plasma sample during APII or saline infusion. Following changes in infusion rates, urine from the first 5 min was discarded, after which a 10-min collection was made. APII (0.5-4 ..mu..g/kg/min) increased water, Na/sup +/ and K/sup +/ output maximally during 2 ..mu..g/kg/min. ERPF decreased from 10.7 +/- 1.1 ml/min to 7.9 +/- 0.5 ml/min. GFR did not change significantly. Filtration fraction increased from 24 +/- 1% to 33 +/- 2%. Fractional water excretion increased from 0.8 +/- 0.2% to 2.5 +/- 0.7%. Saline infusions did not affect renal function. The results indicate that in conscious SHR, APII causes diuresis and natriuresis which does not depend upon increased GFR, but, rather, upon a primary tubular effect.

  12. Visualization of serotonin effects on renal vessels of rats.

    PubMed

    Endlich, K; Kühn, R; Steinhausen, M

    1993-02-01

    We studied the effects of serotonin (5-hydroxytryptamine, 5-HT) on glomerular blood flow (GBF) and on renal vessel diameters in the hydronephrotic kidney and in vascular casts of normal kidneys of rats. 5-HT (60 min after local application of 10(-8) mol.liter-1) constricted the arcuate arteries (-10 +/- 2% to -14 +/- 2%, mean +/- SEM), dilated the interlobular arteries (+13 +/- 2%) and afferent arterioles (+17 +/- 3%), and decreased GBF (-44 +/- 5%). In contrast to normal autoregulation, reduction of renal perfusion pressure after local application of 5-HT from 118 +/- 3 mm Hg by 10 and 20 mm Hg reduced GBF by 12 +/- 2% and 23 +/- 3%, respectively. The 5-HT2 antagonist, ritanserin (60 min after local application of 10(-6) mol.liter-1), dilated all preglomerular vessels and increased GBF. In the presence of ritanserin, 5-HT lost nearly all vascular effects. During infusion of 5-HT (5 micrograms.min-1 i.v. for 20 min) vascular reactions were similar to those under local application. After cyclooxygenase inhibition with indomethacin, infusion of 5-HT failed to constrict the arcuate arteries whereas vasodilation of the small preglomerular vessels remained unaffected. Analyzing vascular casts of normal kidneys we observed considerable vascular spasms and an average vasoconstriction of the interlobar arteries of 19 +/- 9% after i.v. infusion of 5-HT. We believe that 5-HT decreases GBF by 5-HT2 receptor-mediated constriction of the large renal vessels which are modulated by the prostaglandin system, whereas 5-HT dilates the small preglomerular vessels, most likely via 5-HT1-like receptors. Furthermore, our data indicate that 5-HT impairs the myogenic component of renal autoregulation in the low pressure range.

  13. Lycopersicon esculentum (Tomato) Prevents Adverse Effects of Lead on Blood Constituents

    PubMed Central

    SALAWU, Emmanuel O

    2010-01-01

    Background: Lead is known for its adverse effects on various organs and systems. In this study, the ability of lead to adversely affect blood parameters was investigated, and Lycopersicon esculentum, or commonly known as tomato (a source of antioxidants), was administered orally in the form of tomato paste (TP) to reduce the adverse effects of lead. Methods: The study involved 56 Wistar rats divided equally into 4 groups of 14 rats each: Control, LAG, TPG, and LA+TPG. Control and TPG rats were given distilled water ad libitum, while LAG and LA+TPG rats were given 1% lead (II) acetate (LA) per day. TPG and LA+TPG rats were additionally treated with 1.5 ml of TP per day. All treatments lasted for 10 weeks, after which the rats were weighed and sacrificed, and haematological and biochemical parameters were measured. The independent samples t test was used to analyse the results. Results: Lead caused significant reductions in the following parameters: weight; packed cell volume; red blood cell and white blood cell counts; the percentages of lymphocytes and monocytes; total serum protein, albumin, and globulin levels; and plasma superoxide dismutase and catalase activities. In contrast, lead caused a significant increase in the percentage of neutrophils and the plasma malondialdehyde concentration. TP, however, significantly prevented the adverse effects of LA. Conclusion: The oral administration of TP prevents the adverse effects of lead on blood constituents. PMID:22135544

  14. Adverse cardiac effects of exogenous angiotensin 1-7 in rats with subtotal nephrectomy are prevented by ACE inhibition

    PubMed Central

    Griggs, Karen; Patel, Sheila K.

    2017-01-01

    We previously reported that exogenous angiotensin (Ang) 1–7 has adverse cardiac effects in experimental kidney failure due to its action to increase cardiac angiotensin converting enzyme (ACE) activity. This study investigated if the addition of an ACE inhibitor (ACEi) to Ang 1–7 infusion would unmask any beneficial effects of Ang 1–7 on the heart in experimental kidney failure. Male Sprague–Dawley rats underwent subtotal nephrectomy (STNx) and were treated with vehicle, the ACEi ramipril (oral 1mg/kg/day), Ang 1–7 (subcutaneous 24 μg/kg/h) or dual therapy (all groups, n = 12). A control group (n = 10) of sham-operated rats were also studied. STNx led to hypertension, renal impairment, cardiac hypertrophy and fibrosis, and increased both left ventricular ACE2 activity and ACE binding. STNx was not associated with changes in plasma levels of ACE, ACE2 or angiotensin peptides. Ramipril reduced blood pressure, improved cardiac hypertrophy and fibrosis and inhibited cardiac ACE. Ang 1–7 infusion increased blood pressure, cardiac interstitial fibrosis and cardiac ACE binding compared to untreated STNx rats. Although in STNx rats, the addition of ACEi to Ang 1–7 prevented any deleterious cardiac effects of Ang 1–7, a limitation of the study is that the large increase in plasma Ang 1–7 with ramipril may have masked any effect of infused Ang 1–7. PMID:28192475

  15. Renal handling and acute urinary electrolyte effects of aminoglycoside antibiotics: use of a solitary renal autotransplant in the conscious sheep.

    PubMed

    Bennett, W M; McDougall, J; Potocnik, S; Wright, R D; Whitworth, J A

    1983-01-17

    Renal handling of the aminoglycoside antibiotics gentamicin and tobramycin were studied before and after one hour of constant intravenous infusions adjusted to maintain a concentration of 15 micrograms/mL. A solitary renal autotransplant model in four conscious volume replete 40 Kg sheep was used. This unique surgical preparation allows sampling of renal arterial and renal venous blood as well as urine drained through an exteriorized parotid-ureteral fistula. This surgical preparation has considerable potential in renal pharmacology since it uses a conscious, large animal. Baseline studies in this preparation demonstrated normal, 51CrEDTA and 125 I PAH, clearances which were unaffected by the drugs. Aminoglycoside binding to pooled sheep sera was 11% at physiologic PH, calcium and magnesium concentrations. A-V difference was 1.3 +/- .3 micrograms/mL and extraction by the kidney was 9 +/- 3.2% with no differences between gentamicin and tobramycin. Clearance of gentamicin was 84% and tobramycin 86% of GFR. There was no evidence of tubular injury as evidenced by unchanged urinary beta-2 microglobulin excretion. Serum Na, K, Ca and Mg did not change over the course of the study. Both drugs caused a prompt decrease in absolute and fractional sodium excretion while only gentamicin produced a kaliuresis. Early aminoglycoside effects on electrolyte balance may be an eventual determinant of nephrotoxic potential rather than differences in renal drug handling.

  16. Redox nanoparticle therapeutics to cancer--increase in therapeutic effect of doxorubicin, suppressing its adverse effect.

    PubMed

    Yoshitomi, Toru; Ozaki, Yuki; Thangavel, Sindhu; Nagasaki, Yukio

    2013-11-28

    The ultimate goal of cancer chemotherapy is to achieve a cure without causing any adverse effects. We have developed a pH-sensitive redox nanoparticle (RNP(N)), which disintegrates under acidic conditions and exposes nitroxide radicals, leading to strongly scavenging reactive oxygen species (ROS). After intravenous administration of RNP(N) to tumor bearing mice, it effectively accumulated in tumors due to the leaky neovascular and immature lymphatic system and scavenged ROS, resulting in suppression of inflammation and activation of NF-кB, after disintegration of RNP(N) in the tumors. Pre-administration of RNP(N) prior to treatments with anticancer agents, doxorubicin, to tumor-bearing mice significantly suppressed the progression of tumor size, compared to low-molecular weight 4-hydroxy-TEMPO. Interestingly, the administration of RNP(N) suppressed adverse effects of doxorubicin to normal organs due to the scavenging ROS and suppression of inflammation, which was confirmed by reduction in lactate dehydrogenase and creatine phosphokinase activities in plasma. RNP(N) is thus anticipated as a novel and ideal adjuvant for cancer chemotherapy.

  17. Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

    SciTech Connect

    Herrera, Higmar; Yanez, Elvia

    2010-12-07

    This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55{+-}13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher age (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).

  18. A review of the adverse effects and safety of noradrenergic antidepressants.

    PubMed

    Whiskey, Eromona; Taylor, David

    2013-08-01

    There are a variety of noradrenergic antidepressants available, most of which act by inhibiting neuronal noradrenaline re-uptake, although few drugs are specific for this action. Where drugs have numerous actions the adverse effects of noradrenaline reuptake may be difficult to isolate, although in this respect the adverse effects of reboxetine, a specific noradrenaline re-uptake inhibitor, are illuminating. Noradrenergic antidepressants typically cause minor changes in blood and heart rate, sweating and insomnia. Other pharmacological actions shown by non-specific antidepressants may act to worsen or mitigate these adverse effects. Noradrenergic drugs are less likely than selective serotonin reuptake inhibitors (SSRIs) to cause sexual dysfunction but more likely to cause urinary hesitancy. Doubts remain over the relative propensity for antidepressants with different modes of action to cause diabetes and hyponatraemia. Noradrenergic actions do not seem to confer a risk of death in overdose.

  19. Effect of Ramipril on Urinary Protein Excretion in Maintenance Renal Transplant Patients Converted to Sirolimus.

    PubMed

    Mandelbrot, D A; Alberú, J; Barama, A; Marder, B A; Silva, H T; Flechner, S M; Flynn, A; Healy, C; Li, H; Tortorici, M A; Schulman, S L

    2015-12-01

    This prospective, randomized, double-blind, placebo-controlled study evaluated the effects of ramipril on urinary protein excretion in renal transplant patients treated with sirolimus following conversion from a calcineurin inhibitor. Patients received ramipril or placebo for up to 6 weeks before conversion and 52 weeks thereafter. Doses were increased if patients developed proteinuria (urinary protein/creatinine ratio ≥0.5); losartan was given as rescue therapy for persistent proteinuria. The primary end point was time to losartan initiation. Of 295 patients randomized, 264 met the criteria for sirolimus conversion (ramipril, 138; placebo, 126). At 52 weeks, the cumulative rate of losartan initiation was significantly lower with ramipril (6.2%) versus placebo (23.2%) (p < 0.001). No significant differences were observed between ramipril and placebo for change in glomerular filtration rate from baseline (p = 0.148) or in the number of patients with biopsy-confirmed acute rejection (13 vs. 5, respectively; p = 0.073). One patient in the placebo group died due to cerebrovascular accident. Treatment-emergent adverse events were consistent with the known safety profile of sirolimus and were not potentiated by ramipril co-administration. Ramipril was effective in reducing the incidence of proteinuria for up to 1 year following conversion to sirolimus in maintenance renal transplant patients.

  20. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., respiratory, oral). (B) List signs/symptoms/adverse effects. (C) If laboratory tests were performed, list name... effect). (D) Route of exposure (e.g., skin, eye, respiratory, oral). (E) Time between exposure and onset... of systems supplied. (C) If finished water samples, water supply systems sampled. (D) If...

  1. On the Likelihood of Single-Walled Carbon Nanotubes Causing Adverse Marine Ecological Effects

    EPA Science Inventory

    This brief article discusses the ecological effects of single-walled carbon nanotubes (SWNTs)in the marine environment. Based on new research and a review of the scientific literature, the paper concludes that SWNTs are unlikely to cause adverse ecological effects in the marine ...

  2. The College Student and Marijuana: Research Findings Concerning Adverse Biological and Psychological Effects.

    ERIC Educational Resources Information Center

    Nicholi, Armand M., Jr.

    1983-01-01

    This paper focuses on current knowledge about adverse biological and psychological affects of marijuana use, with special reference to risks for college students. Short-term effects on intellectual functioning and perceptual-motor coordination and long-term effects on reproduction and motivation are highlighted. (PP)

  3. Mechanism of renal effects of intracerebroventricular histamine in rabbits.

    PubMed

    Kook, Y J; Kim, K K; Yang, D K; Ahn, D S; Choi, B K

    1988-01-01

    Histamine, when given intracerebroventricularly (i.c.v.), has been reported to produce antidiuresis in the rabbit. In this study it was attempted to elucidate the mechanism involved in the effect. Histamine (H), 100 micrograms/kg i.c.v., produced antidiuresis with decreases in renal plasma flow and glomerular filtration rate in urethane-anesthetized rabbits. With larger doses, a tendency towards increased electrolyte excretion was noted in spite of decreased filtration. In the denervated kidney, marked diuresis and natriuresis were observed following i.c.v. H, whereas the contralateral innervated kidney responded with typical antidiuresis. Reserpinized rabbits also responded with marked natriuresis to i.c.v. H. Diphenhydramine (D), 250 micrograms/kg i.c.v., increased urine flow rate, sodium and potassium excretion, along with increase in renal perfusion. With 750 micrograms/kg i.c.v., marked natriuresis was observed in spite of decreased filtration. When H was given after D (250 micrograms/kg) the antidiuresis was completely abolished, and diuresis became more prominent. Cimetidine, 250 micrograms/kg i.c.v., elicited antidiuresis with decreases in renal hemodynamics, the pretreatment with cimetidine did not influence the antidiuresis by H and no natriuresis was noted. The present study suggests that histamine, given i.c.v., influences renal function in dual ways, i.e., antidiuresis by increasing the sympathetic tone to the kidney and diuresis due to some humoral natriuretic factor, the latter becoming apparent only when the former influence has been removed, and further suggests that H1-receptors might be involved in the nerve-mediated antidiuresis, whereas H2-receptors might mediate the humorally induced natriuresis and diuresis.

  4. Short-term medical benefits and adverse effects of weight loss.

    PubMed

    Pi-Sunyer, F X

    1993-10-01

    Weight loss reduces many of the health hazards associated with obesity including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, sleep apnea, hypoxemia and hypercarbia, and osteoarthritis. Potential adverse effects of weight loss include a greater risk for gallstone formation and cholecystitis, excessive loss of lean body mass, water and electrolyte problems, mild liver dysfunction, and elevated uric acid levels. Less consequential problems such as diarrhea, constipation, hair loss, and cold intolerance may also occur. The short-term adverse effects are not severe enough to contraindicate weight loss, nor do they outweigh its short-term benefits.

  5. The effects of renal impairment on the pharmacokinetics, safety, and tolerability of naloxegol.

    PubMed

    Bui, Khanh; She, Fahua; Sostek, Mark

    2014-12-01

    The impact of renal impairment on the pharmacokinetics of a 25-mg oral dose of naloxegol was examined in patients with renal impairment classified as moderate, severe, or end-stage renal disease (ESRD) and compared with healthy subjects (n = 8/group). Geometric mean area under the plasma concentration-time curve (AUC) was increased in patients with moderate (1.7-fold) or severe (2.2-fold) impairment, and maximum plasma concentrations (Cmax ) were elevated in patients with moderate (1.1-fold) or severe (1.8-fold) impairment. These findings were driven by higher exposures in two patients in each of the moderate and severe impairment groups; exposures in all other patients were similar to the control group. Overall exposures in ESRD patients were similar and Cmax was 29% lower versus normal subjects. Renal impairment minimally affected other plasma pharmacokinetic parameters. As renal clearance was a minor component of total clearance, exposure to naloxegol was unaffected by the degree of renal impairment, with no correlation between either AUC or Cmax and estimated glomerular filtration rate (eGFR). Hemodialysis was an ineffective means to remove naloxegol. Naloxegol was generally well tolerated in all groups. Renal impairment could adversely affect clearance by hepatic and gut metabolism, resulting in the increased exposures observed in outliers of the moderate and severe renal impairment groups.

  6. Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, nonrandomized study

    PubMed Central

    Mehta, Rashmi; Hardes, Kelly; Brealey, Noushin; Tombs, Lee; Preece, Andrew; Kelleher, Dennis

    2015-01-01

    Background Umeclidinium and vilanterol, long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease, are primarily eliminated via the hepatic route; however, severe renal impairment may adversely affect some elimination pathways other than the kidney. Objectives To evaluate the effect of severe renal impairment on the pharmacokinetics of umeclidinium and umeclidinium/vilanterol. Methods Nine patients with severe renal impairment (creatinine clearance <30 mL/min) and nine matched healthy volunteers received a single dose of umeclidinium 125 μg; and after a 7- to 14-day washout, a single dose of umeclidinium/vilanterol 125/25 μg. Results No clinically relevant increases in plasma umeclidinium or vilanterol systemic exposure (area under the curve or maximum observed plasma concentration) were observed following umeclidinium 125 μg or umeclidinium/vilanterol 125/25 μg administration. On average, the amount of umeclidinium excreted in 24 hours in urine (90% confidence interval) was 88% (81%–93%) and 89% (81%–93%) lower in patients with severe renal impairment compared with healthy volunteers following umeclidinium 125 μg and umeclidinium/vilanterol 125/25 μg administration, respectively. Treatments were well tolerated in both populations. Conclusion Umeclidinium 125 μg or umeclidinium/vilanterol 125/25 μg administration to patients with severe renal impairment did not demonstrate clinically relevant increases in systemic exposure compared with healthy volunteers. No dose adjustment for umeclidinium and umeclidinium/vilanterol is warranted in patients with severe renal impairment. PMID:25565796

  7. A replication of the study ‘Adverse effects of spinal manipulation: a systematic review’

    PubMed Central

    2012-01-01

    and related adverse effects. PMID:22998971

  8. Post-Finasteride Adverse Effects in Male Androgenic Alopecia: A Case Report of Vitiligo.

    PubMed

    Motofei, Ion G; Rowland, David L; Georgescu, Simona R; Tampa, Mircea; Paunica, Stana; Constantin, Vlad D; Balalau, Cristian; Manea, Mirela; Baleanu, Bogdan C; Sinescu, Ioanel

    2017-01-01

    Finasteride has proved to be relatively safe and effective in the therapeutic management of male androgenic alopecia. However, literature data report several endocrine imbalances inducing various adverse effects, which often persist after treatment cessation in the form of post-finasteride syndrome. Here we present the case of a 52-year-old man receiving finasteride (1 mg/day) who developed an uncommon adverse effect represented by generalized vitiligo 2 months after finasteride discontinuation. Associated adverse effects encountered were represented by mild sexual dysfunction (as determined by the International Index of Erectile Function, IIEF) and moderate depressive symptoms (according to DSM-V criteria), all of these manifestations aggregating within/as a possible post-finasteride syndrome. Further studies should develop and compare several therapeutic approaches, taking into account not only compounds that decrease the circulating dihydrotestosterone level but also those that could block the dihydrotestosterone receptors (if possible, compounds with selective tropism towards the skin). In addition, the possibility of predicting adverse effects of finasteride (according to hand preference and sexual orientation) should be taken into account.

  9. Renal Expression of FGF23 in Progressive Renal Disease of Diabetes and the Effect of Ace Inhibitor

    PubMed Central

    Benigni, Ariela; Corna, Daniela; Tomasoni, Susanna; Rottoli, Daniela; Gaspari, Flavio; Remuzzi, Giuseppe; Zoja, Carlamaria

    2013-01-01

    Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone mainly produced by bone that acts in the kidney through FGF receptors and Klotho. Here we investigated whether the kidney was an additional source of FGF23 during renal disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23 and Klotho was assessed in Zucker diabetic fatty (ZDF) and control lean rats at 2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of angiotensin converting enzyme (ACE) inhibitor in this model was associated with changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric, to 8 months of age. FGF23 mRNA was not detectable in the kidney of lean rats, nor of ZDF rats at 2 months of age. FGF23 became measurable in the kidney of diabetic rats at 4 months and significantly increased thereafter. FGF23 protein localized in proximal and distal tubules. Renal Klotho mRNA and protein decreased during time in ZDF rats. As renal disease progressed, serum phosphate levels increased in parallel with decline of fractional phosphorus excretion. Ramipril limited proteinuria and renal injury, attenuated renal FGF23 upregulation and ameliorated Klotho expression. Ramipril normalized serum phosphate levels and tended to increase fractional phosphorus excretion. These data indicate that during progressive renal disease the kidney is a site of FGF23 production which is limited by ACE inhibition. Interfering pharmacologically with the delicate balance of FGF23 and phosphorus in diabetes may have implications in clinics. PMID:23967103

  10. The Role of Mindfulness in Reducing the Adverse Effects of Childhood Stress and Trauma

    PubMed Central

    Ortiz, Robin; Sibinga, Erica M.

    2017-01-01

    Research suggests that many children are exposed to adverse experiences in childhood. Such adverse childhood exposures may result in stress and trauma, which are associated with increased morbidity and mortality into adulthood. In general populations and trauma-exposed adults, mindfulness interventions have demonstrated reduced depression and anxiety, reduced trauma-related symptoms, enhanced coping and mood, and improved quality of life. Studies in children and youth also demonstrate that mindfulness interventions improve mental, behavioral, and physical outcomes. Taken together, this research suggests that high-quality, structured mindfulness instruction may mitigate the negative effects of stress and trauma related to adverse childhood exposures, improving short- and long-term outcomes, and potentially reducing poor health outcomes in adulthood. Future work is needed to optimize implementation of youth-based mindfulness programs and to study long-term outcomes into adulthood. PMID:28264496

  11. The Role of Mindfulness in Reducing the Adverse Effects of Childhood Stress and Trauma.

    PubMed

    Ortiz, Robin; Sibinga, Erica M

    2017-02-28

    Research suggests that many children are exposed to adverse experiences in childhood. Such adverse childhood exposures may result in stress and trauma, which are associated with increased morbidity and mortality into adulthood. In general populations and trauma-exposed adults, mindfulness interventions have demonstrated reduced depression and anxiety, reduced trauma-related symptoms, enhanced coping and mood, and improved quality of life. Studies in children and youth also demonstrate that mindfulness interventions improve mental, behavioral, and physical outcomes. Taken together, this research suggests that high-quality, structured mindfulness instruction may mitigate the negative effects of stress and trauma related to adverse childhood exposures, improving short- and long-term outcomes, and potentially reducing poor health outcomes in adulthood. Future work is needed to optimize implementation of youth-based mindfulness programs and to study long-term outcomes into adulthood.

  12. Late-onset Tay-Sachs disease: adverse effects of medications and implications for treatment.

    PubMed

    Shapiro, B E; Hatters-Friedman, S; Fernandes-Filho, J A; Anthony, K; Natowicz, M R

    2006-09-12

    The authors conducted a retrospective and brief prospective study of adverse effects of approximately 350 medications in 44 adults with late-onset Tay-Sachs disease (LOTS). Some medications were relatively safe, whereas others, particularly haloperidol, risperidone, and chlorpromazine, were associated with neurologic worsening.

  13. Potassium fertilization mitigates the adverse effects of drought on selected Zea mays cultivars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the present study, the role of potassium (K) in mitigating the adverse effects of drought stress (DS) on 2 maize (Zea mays L.) cultivars, ‘Shaandan 9’ (S9; drought-tolerant) and ‘Shaandan 911’ (S911; drought-sensitive), was assessed. K application increased dry matter (DM) across all growth stage...

  14. ENVIRONMENTAL POLLUTANTS AND ADVERSE HUMAN HEALTH EFFECTS: HAZARD IDENTIFICATION USING INTERREGION COMPARISONS

    EPA Science Inventory

    Background: Associations between adverse health effects and environmental exposures are difficult to study, because exposures may be widespread, low-dose in nature, and common throughout the study population. Therefore, individual risk-factor epidemiology may not be the right to...

  15. Caregiver Acceptance of Adverse Effects and Use of Cholinesterase Inhibitors in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Oremus, Mark; Wolfson, Christina; Vandal, Alain C.; Bergman, Howard; Xie, Qihao

    2007-01-01

    Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire…

  16. ARE ENVIRONMENTAL EXPOSURES TO CHLOROPHENOXY HERBICIDES ASSOCIATED WITH AN INCREASE IN ADVERSE HUMAN HEALTH EFFECTS?

    EPA Science Inventory

    Background: Associations between adverse health effects and environmental exposures are difficult to study because exposures may be widespread, low-dose in nature, and common throughout the study population. Individual risk-factor epidemiology may not be able to initially ident...

  17. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Flagging of studies for potential... Provisions § 161.34 Flagging of studies for potential adverse effects. (a) Any person who submits a study of... registration, or to satisfy a requirement imposed under FIFRA sec. 3(c)(2)(B), must submit with the study...

  18. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Flagging of studies for potential... Provisions § 161.34 Flagging of studies for potential adverse effects. (a) Any person who submits a study of... registration, or to satisfy a requirement imposed under FIFRA sec. 3(c)(2)(B), must submit with the study...

  19. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Flagging of studies for potential... Provisions § 161.34 Flagging of studies for potential adverse effects. (a) Any person who submits a study of... registration, or to satisfy a requirement imposed under FIFRA sec. 3(c)(2)(B), must submit with the study...

  20. Adverse Effect of Child Abuse Victimization among Substance-Using Women in Treatment.

    ERIC Educational Resources Information Center

    Kang, Sung-Yeon; Magura, Stephen; Laudet, Alexandre; Whitney, Shirley

    1999-01-01

    Study examined adverse effects of childhood sexual/physical abuse among substance-abusing women with children. Several significant differences between abused and nonabused women were found in service outcomes. Abused women had more problems relating to drug use and psychiatric/psychological adjustment at follow-up. Findings support a need for…

  1. The Risk of Adverse Impact in Selections Based on a Test with Known Effect Size

    ERIC Educational Resources Information Center

    De Corte, Wilfried; Lievens, Filip

    2005-01-01

    The authors derive the exact sampling distribution function of the adverse impact (AI) ratio for single-stage, top-down selections using tests with known effect sizes. Subsequently, it is shown how this distribution function can be used to determine the risk that a future selection decision on the basis of such tests will result in an outcome that…

  2. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    PubMed Central

    Croft, Ashley M; Herxheimer, Andrew

    2002-01-01

    Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis. PMID:11914150

  3. Genetic Predictors of Adverse Radiotherapy Effects: The Gene-PARE project

    SciTech Connect

    Ho, Alice Y.; Atencio, David P.; Peters, Sheila; Stock, Richard G.; Cesaretti, Jamie A.; Green, Sheryl; Formenti, Silvia C.; Haffty, Bruce; Drumea, Karen; Leitzin, Larisa M.D.; Kuten, Abraham; Azria, David; Ozsahin, Mahmut; Overgaard, Jens; Andreassen, Christian N.; Trop, Cynthia S.; Park, Janelle; Rosenstein, Barry S. |||. E-mail: barry.rosenstein@mssm.edu

    2006-07-01

    Purpose: The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of specific genetic variants, would therefore be of value. The purpose of the Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE) project is to help achieve this goal. Methods and Materials: A continuously expanding biorepository has been created consisting of frozen lymphocytes and DNA isolated from patients treated with radiotherapy. In conjunction with this biorepository, a database is maintained with detailed clinical information pertaining to diagnosis, treatment, and outcome. The DNA samples are screened using denaturing high performance liquid chromatography (DHPLC) and the Surveyor nuclease assay for variants in ATM, TGFB1, XRCC1, XRCC3, SOD2, and hHR21. It is anticipated that additional genes that control the biologic response to radiation will be screened in future work. Results: Evidence has been obtained that possession of variants in genes, the products of which play a role in radiation response, is predictive for the development of adverse effects after radiotherapy. Conclusions: It is anticipated that the Gene-PARE project will yield information that will allow radiation oncologists to use genetic data to optimize treatment on an individual basis.

  4. The adverse effects of long-term l-carnitine supplementation on liver and kidney function in rats.

    PubMed

    Liu, L; Zhang, D-M; Wang, M-X; Fan, C-Y; Zhou, F; Wang, S-J; Kong, L-D

    2015-11-01

    Levo-Carnitine (l-carnitine) is widely used in health and food. This study was to focus on the adverse effects of 8-week oral supplementation of l-carnitine (0.3 and 0.6 g/kg) in female and male Sprague Dawley rats. l-carnitine reduced body and fat weights, as well as serum, liver, and kidney lipid levels in rats. Simultaneously, hepatic fatty acid β-oxidation and lipid synthesis were disturbed in l-carnitine-fed rats. Moreover, l-carnitine accelerated reactive oxygen species production in serum and liver, thereby triggering hepatic NOD-like receptor 3 (NLRP3) inflammasome activation to elevate serum interleukin (IL)-1β and IL-18 levels in rats. Alteration of serum alkaline phosphatase levels further confirmed liver dysfunction in l-carnitine-fed rats. Additionally, l-carnitine may potentially disturb kidney function by altering renal protein levels of rat organic ion transporters. These observations may provide the caution information for the safety of long-term l-carnitine supplementation.

  5. Renal Denervation Normalizes Arterial Pressure With No Effect on Glucose Metabolism or Renal Inflammation in Obese Hypertensive Mice.

    PubMed

    Asirvatham-Jeyaraj, Ninitha; Fiege, Jessica K; Han, Ruijun; Foss, Jason; Banek, Christopher T; Burbach, Brandon J; Razzoli, Maria; Bartolomucci, Alessandro; Shimizu, Yoji; Panoskaltsis-Mortari, Angela; Osborn, John W

    2016-10-01

    Hypertension often occurs in concurrence with obesity and diabetes mellitus, commonly referred to as metabolic syndrome. Renal denervation (RDNx) lowers arterial pressure (AP) and improves glucose metabolism in drug-resistant hypertensive patients with high body mass index. In addition, RDNx has been shown to reduce renal inflammation in the mouse model of angiotensin II hypertension. The present study tested the hypothesis that RDNx reduces AP and renal inflammation and improves glucose metabolism in obesity-induced hypertension. Eight-week-old C57BL/6J mice were fed either a low-fat diet (10 kcal%) or a high-fat diet (45 kcal%) for 10 weeks. Body weight, food intake, fasting blood glucose, and glucose metabolism (glucose tolerance test) were measured. In a parallel study, radiotelemeters were implanted in mice for AP measurement. High fat-fed C57BL/6J mice exhibited an inflammatory and metabolic syndrome phenotype, including increased fat mass, increased AP, and hyperglycemia compared with low-fat diet mice. RDNx, but not Sham surgery, normalized AP in high-fat diet mice (115.8±1.5 mm Hg in sham versus 96.6±6.7 mm Hg in RDNx). RDNx had no significant effect on AP in low-fat diet mice. Also, RDNx had no significant effect on glucose metabolism or renal inflammation as measured by the number of CD8, CD4, and T helper cells or levels of inflammatory cytokines in the kidneys. These results indicate that although renal nerves play a role in obesity-induced hypertension, they do not contribute to impaired glucose metabolism or renal inflammation in this model.

  6. Quality of life and adverse effects of olanzapine versus risperidone therapy in patients with schizophrenia.

    PubMed

    Chaves, Katarina Melo; Serrano-Blanco, Antoni; Ribeiro, Susana Barbosa; Soares, Luiz Alberto Lira; Guerra, Gerlane Coelho Bernardo; do Socorro Costa Feitosa Alves, Maria; de Araújo Júnior, Raimundo Fernandes; de Paula Soares Rachetti, Vanessa; Filgueira Júnior, Antônio; de Araújo, Aurigena Antunes

    2013-03-01

    This cross-sectional study aimed to compare the effects of treatment with an atypical antipsychotic drug (olanzapine or risperidone) on quality of life (QoL) and to document adverse effects in 115 patients diagnosed with schizophrenia who attended the ambulatory service of Hospital Dr. João Machado, Natal, Rio Grande do Norte, Brazil. Socioeconomic, sociodemographic, and clinical variables were compared. The QoL Scale validated for Brazil (QLS-BR) was used to evaluate QoL, and adverse effects were assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Data were analyzed using the χ(2) test and Student's t test, with a significance level of 5 %. Patients in both drug groups showed severe impairment in the occupational domain of the QLS-BR. Global QLS-BR scores indicated impairment among risperidone users and severe impairment among olanzapine users. The most significant side effects were associated with risperidone, including asthenia/lassitude/fatigue, somnolence/sedation, paresthesia, change in visual accommodation, increased salivation, diarrhea, orthostatic posture, palpitations/tachycardia, erythema, photosensitivity, weight loss, galactorrhea, decreased sexual desire, erectile/orgasmic dysfunction, vaginal dryness, headache, and physical dependence. QoL was impaired in patients using olanzapine and in those using risperidone. Risperidone use was associated with psychic, neurological, and autonomous adverse effects and other side effects.

  7. From the exposome to mechanistic understanding of chemical-induced adverse effects.

    PubMed

    Escher, Beate I; Hackermüller, Jörg; Polte, Tobias; Scholz, Stefan; Aigner, Achim; Altenburger, Rolf; Böhme, Alexander; Bopp, Stephanie K; Brack, Werner; Busch, Wibke; Chadeau-Hyam, Marc; Covaci, Adrian; Eisenträger, Adolf; Galligan, James J; Garcia-Reyero, Natalia; Hartung, Thomas; Hein, Michaela; Herberth, Gunda; Jahnke, Annika; Kleinjans, Jos; Klüver, Nils; Krauss, Martin; Lamoree, Marja; Lehmann, Irina; Luckenbach, Till; Miller, Gary W; Müller, Andrea; Phillips, David H; Reemtsma, Thorsten; Rolle-Kampczyk, Ulrike; Schüürmann, Gerrit; Schwikowski, Benno; Tan, Yu-Mei; Trump, Saskia; Walter-Rohde, Susanne; Wambaugh, John F

    2017-02-01

    The exposome encompasses an individual's exposure to exogenous chemicals, as well as endogenous chemicals that are produced or altered in response to external stressors. While the exposome concept has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. Here, we explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept that structures and organizes the sequence of biological events from an initial molecular interaction of a chemical with a biological target to an adverse outcome. Complementing exposome research with the AOP concept may facilitate a mechanistic understanding of stress-induced adverse effects, examine the relative contributions from various components of the exposome, determine the primary risk drivers in complex mixtures, and promote an integrative assessment of chemical risks for both human and environmental health.

  8. Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China

    PubMed Central

    Wu, Junyi; Hu, Yanmei; Zhu, Yin; Yin, Ping; Litscher, Gerhard; Xu, Shifen

    2015-01-01

    As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world. PMID:26339265

  9. The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles

    PubMed Central

    Ali, Badreldin H; Shalaby, Asem; Manoj, Priyadarsini; Waly, Mostafa I; Yasin, Javed; Fahim, Mohamed; Nemmar, Abderrahim

    2015-01-01

    Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24 h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6 mg/kg) and four days later, they were exposed intratracheally to DEP (0.5 mg/kg), and were sacrificed 24 h later. Oral TQ (20 mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP. PMID:25925792

  10. Effects of the antioxidant drug tempol on renal oxygenation in mice with reduced renal mass.

    PubMed

    Lai, En Yin; Luo, Zaiming; Onozato, Maristela L; Rudolph, Earl H; Solis, Glenn; Jose, Pedro A; Wellstein, Anton; Aslam, Shakil; Quinn, Mark T; Griendling, Kathy; Le, Thu; Li, Ping; Palm, Fredrik; Welch, William J; Wilcox, Christopher S

    2012-07-01

    We tested the hypothesis that reactive oxygen species (ROS) contributed to renal hypoxia in C57BL/6 mice with ⅚ surgical reduction of renal mass (RRM). ROS can activate the mitochondrial uncoupling protein 2 (UCP-2) and increase O(2) usage. However, UCP-2 can be inactivated by glutathionylation. Mice were fed normal (NS)- or high-salt (HS) diets, and HS mice received the antioxidant drug tempol or vehicle for 3 mo. Since salt intake did not affect the tubular Na(+) transport per O(2) consumed (T(Na/)Q(O2)), further studies were confined to HS mice. RRM mice had increased excretion of 8-isoprostane F(2α) and H(2)O(2), renal expression of UCP-2 and renal O(2) extraction, and reduced T(Na/)Q(O2) (sham: 20 ± 2 vs. RRM: 10 ± 1 μmol/μmol; P < 0.05) and cortical Po(2) (sham: 43 ± 2, RRM: 29 ± 2 mmHg; P < 0.02). Tempol normalized all these parameters while further increasing compensatory renal growth and glomerular volume. RRM mice had preserved blood pressure, glomeruli, and patchy tubulointerstitial fibrosis. The patterns of protein expression in the renal cortex suggested that RRM kidneys had increased ROS from upregulated p22(phox), NOX-2, and -4 and that ROS-dependent increases in UCP-2 led to hypoxia that activated transforming growth factor-β whereas erythroid-related factor 2 (Nrf-2), glutathione peroxidase-1, and glutathione-S-transferase mu-1 were upregulated independently of ROS. We conclude that RRM activated distinct processes: a ROS-dependent activation of UCP-2 leading to inefficient renal O(2) usage and cortical hypoxia that was offset by Nrf-2-dependent glutathionylation. Thus hypoxia in RRM may be the outcome of NADPH oxidase-initiated ROS generation, leading to mitochondrial uncoupling counteracted by defense pathways coordinated by Nrf-2.

  11. Mechanism of glucocorticoid effect on renal transport of phosphate.

    PubMed

    Turner, S T; Kiebzak, G M; Dousa, T P

    1982-11-01

    We explored whether glucocorticoid administration, a known stimulus of renal gluconeogenesis (GNG), could decrease avid inorganic phosphate (Pi) reabsorption in rats stabilized on low-phosphorus diet (LPD). Rats adapted to LPD were injected with the glucocorticoid (GCD) triamcinolone acetonide (1.25 or 2.5 mg.100 g body wt-1.day-1 ip) for 2 days; they showed a profound increase in urinary excretion of Pi during the injection period. In clearance studies GCD increased the clearance and fractional excretion of Pi but did not change the filtered load of Pi. Initial "uphill" Na+-gradient (Nao+ greater than Nai+)-dependent uptake of 32Pi by luminal brush-border membrane (BBM) vesicles prepared from renal cortex of rats treated with GCD was markedly (greater than 40%) decreased compared with control rats; Na+-gradient-dependent uptake of D-[3H]glucose was not diminished. At the "equilibrium" time interval, measured at 120 min, BBM vesicles from control and GCD-treated rats did not differ in the uptake of 32Pi or D-[3H]glucose. With kinetic analysis, BBM from GCD-treated rats showed a marked decrease (-40%) in the maximum velocity (Vmax) of initial Na+-dependent 32Pi uptake, but the apparent affinity of the BBM transport system for Pi (apparent Km = 0.078 mM Pi) was not different from that of controls. Alkaline phosphatase specific activity was much lower (-40%) in BBM from GCD-treated rats compared with controls, but the activities of three other BBM enzymes (maltase, leucine aminopeptidase, and gamma-glutamyl transferase) were not different. The addition of triamcinolone to BBM in vitro had no effect on either Na+-dependent uptake of 32Pi or alkaline phosphatase activity. The rate of GNG from alpha-ketoglutarate was significantly increased in cortical slices from GCD-treated rats adapted to LPD. Also, the NAD+-to-NADH ratio was higher in the renal cortex of GCD-treated rats, although the total content of NAD [NAD+ + NADH] was not different from controls. Renal excretory

  12. In Silico Elucidation of the Molecular Mechanism Defining the Adverse Effect of Selective Estrogen Receptor Modulators

    PubMed Central

    Xie, Lei; Wang, Jian; Bourne, Philip E

    2007-01-01

    Early identification of adverse effect of preclinical and commercial drugs is crucial in developing highly efficient therapeutics, since unexpected adverse drug effects account for one-third of all drug failures in drug development. To correlate protein–drug interactions at the molecule level with their clinical outcomes at the organism level, we have developed an integrated approach to studying protein–ligand interactions on a structural proteome-wide scale by combining protein functional site similarity search, small molecule screening, and protein–ligand binding affinity profile analysis. By applying this methodology, we have elucidated a possible molecular mechanism for the previously observed, but molecularly uncharacterized, side effect of selective estrogen receptor modulators (SERMs). The side effect involves the inhibition of the Sacroplasmic Reticulum Ca2+ ion channel ATPase protein (SERCA) transmembrane domain. The prediction provides molecular insight into reducing the adverse effect of SERMs and is supported by clinical and in vitro observations. The strategy used in this case study is being applied to discover off-targets for other commercially available pharmaceuticals. The process can be included in a drug discovery pipeline in an effort to optimize drug leads and reduce unwanted side effects. PMID:18052534

  13. Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

    PubMed Central

    Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

    2016-01-01

    Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal

  14. Rational therapy for diabetes: early recognition of adverse effects and avoidance of disruptive false alarms.

    PubMed

    Raz, Itamar; Eldor, Roy

    2012-05-01

    Corresponding to the uncontrolled diabetes pandemic, significant effort has been invested in developing new therapeutic options. Nevertheless, all medicines have possible adverse effects. Recently, a trend of 'scrutinizing' novel hypoglycaemic drug side effects based on scant scientific data has emerged. With recent publications highlighting possible dangers of rosiglitazone, insulin glargine, sitagliptin, exenatide and, most recently, pioglitazone, it seems that all means are valid and that every database is suitable, even if specifically defined as inadequate for the purpose of data analysis. The use of such data may lead authors to draw erroneous conclusions that may be granted unwarranted impact upon publication in leading scientific journals and eventually lead patients and misinformed physicians to wrongly change beneficial medication regimes. Adherence to strict scientific methodology, ongoing large clinical trials and creating adjudicated patient databases may facilitate early recognition of adverse effects while avoiding disruptive false alarms.

  15. General and specific effects of early-life psychosocial adversities on adolescent grey matter volume☆

    PubMed Central

    Walsh, Nicholas D.; Dalgleish, Tim; Lombardo, Michael V.; Dunn, Valerie J.; Van Harmelen, Anne-Laura; Ban, Maria; Goodyer, Ian M.

    2014-01-01

    Exposure to childhood adversities (CA) is associated with subsequent alterations in regional brain grey matter volume (GMV). Prior studies have focused mainly on severe neglect and maltreatment. The aim of this study was to determine in currently healthy adolescents if exposure to more common forms of CA results in reduced GMV. Effects on brain structure were investigated using voxel-based morphometry in a cross-sectional study of youth recruited from a population-based longitudinal cohort. 58 participants (mean age = 18.4) with (n = 27) or without (n = 31) CA exposure measured retrospectively from maternal interview were included in the study. Measures of recent negative life events (RNLE) recorded at 14 and 17 years, current depressive symptoms, gender, participant/parental psychiatric history, current family functioning perception and 5-HTTLPR genotype were covariates in analyses. A multivariate analysis of adversities demonstrated a general association with a widespread distributed neural network consisting of cortical midline, lateral frontal, temporal, limbic, and cerebellar regions. Univariate analyses showed more specific associations between adversity measures and regional GMV: CA specifically demonstrated reduced vermis GMV and past psychiatric history with reduced medial temporal lobe volume. In contrast RNLE aged 14 was associated with increased lateral cerebellar and anterior cingulate GMV. We conclude that exposure to moderate levels of childhood adversities occurring during childhood and early adolescence exerts effects on the developing adolescent brain. Reducing exposure to adverse social environments during early life may optimize typical brain development and reduce subsequent mental health risks in adult life. PMID:25061568

  16. Mining multi-item drug adverse effect associations in spontaneous reporting systems

    PubMed Central

    2010-01-01

    Background Multi-item adverse drug event (ADE) associations are associations relating multiple drugs to possibly multiple adverse events. The current standard in pharmacovigilance is bivariate association analysis, where each single drug-adverse effect combination is studied separately. The importance and difficulty in the detection of multi-item ADE associations was noted in several prominent pharmacovigilance studies. In this paper we examine the application of a well established data mining method known as association rule mining, which we tailored to the above problem, and demonstrate its value. The method was applied to the FDAs spontaneous adverse event reporting system (AERS) with minimal restrictions and expectations on its output, an experiment that has not been previously done on the scale and generality proposed in this work. Results Based on a set of 162,744 reports of suspected ADEs reported to AERS and published in the year 2008, our method identified 1167 multi-item ADE associations. A taxonomy that characterizes the associations was developed based on a representative sample. A significant number (67% of the total) of potential multi-item ADE associations identified were characterized and clinically validated by a domain expert as previously recognized ADE associations. Several potentially novel ADEs were also identified. A smaller proportion (4%) of associations were characterized and validated as known drug-drug interactions. Conclusions Our findings demonstrate that multi-item ADEs are present and can be extracted from the FDA’s adverse effect reporting system using our methodology, suggesting that our method is a valid approach for the initial identification of multi-item ADEs. The study also revealed several limitations and challenges that can be attributed to both the method and quality of data. PMID:21044365

  17. 75 FR 7293 - Temporary Agricultural Employment of H-2A Workers in the United States: 2010 Adverse Effect Wage...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

    ... collective bargaining rate, or the Federal or State minimum wage rate, in effect at the time work is...: 2010 Adverse Effect Wage Rates, Allowable Charges for Agricultural Workers' Meals, and Maximum Travel... Department of Labor (Department) is issuing this Notice to announce the new 2010 Adverse Effect Wage...

  18. Adverse effects of industrial multiwalled carbon nanotubes on human pulmonary cells

    PubMed Central

    Tabet, Lyes; Bussy, Cyrill; Amara, Nadia; Setyan, Ari; Grodet, Alain; Rossi, Michel J.; Pairon, Jean-Claude; Boczkowski, Jorge; Lanone, Sophie

    2009-01-01

    The aim of this study was to evaluate adverse effects of multi-walled carbon nanotubes (MWCNT) produced for industrial purposes, on the human epithelial cell line A549. MWCNT were dispersed in dipalmitoyl lecithin (DPL), a component of pulmonary surfactant, and the effects of dispersion in DPL were compared to those in 2 other media: ethanol (EtOH) and phosphate buffer saline (PBS). Effects of MWCNT were also compared to those of 2 asbestos fibers (chrysotile and crocidolite) and carbon black (CB) nanoparticles, not only in A549 cells, but also on mesothelial cells (MeT5A human cell line), used as an asbestos-sensitive cell type. MWCNT formed agglomerates on top of both cell lines (surface area 15–35 μm2), that were significantly larger and more numerous in PBS than in EtOH and DPL. Whatever the dispersion media, incubation with 100 μg/ml MWCNT induced a similar decrease in metabolic activity without changing cell membrane permeability or apoptosis. Neither MWCNT cellular internalization nor oxidative stress were observed. In contrast, asbestos fibers penetrated into the cells, decreased metabolic activity but not cell membrane permeability and increased apoptosis, without decreasing cell number. CB was internalized without any adverse effects. In conclusion, this study demonstrates that MWCNT produced for industrial purposes exert adverse effects without being internalized by human epithelial and mesothelial pulmonary cell lines. PMID:19034795

  19. Renal physiology of nocturia.

    PubMed

    Verbalis, Joseph G

    2014-04-01

    Renal function, diurnal fluctuations in arginine vasopressin (AVP) secretion, sex, and advanced age affect urine formation and may contribute to nocturia. Renal effects of AVP are mediated by AVP V2 receptors in the kidney collecting duct. Changes in AVP concentration have the greatest relative effects on urine volume when AVP levels are low; therefore small changes can have a large effect on renal water excretion. AVP is the major regulator of water excretion by the kidneys, and AVP levels have been shown to affect nocturnal voiding. Results of several studies show that patients with nocturia had no significant variation in plasma AVP, whereas patients without nocturia had significant diurnal variation in plasma AVP. The V2 receptor gene is located on the X chromosome, which has important sex-specific consequences. For example, mutations in the V2 gene can cause nephrogenic diabetes insipidus, predominantly in men. Age-related changes in water metabolism are associated with overall body composition, kidney, and brain. Older people generally experience decreased extracellular fluid and plasma volume, which leads to increased adverse consequences from net body water gain or loss. Renal function declines with age, and the ability to concentrate urine and conserve sodium is reduced in the elderly. Thirst perception is also decreased in the elderly, who, compared with younger people, tend to hypersecrete AVP in response to higher plasma osmolality, possibly resulting in hyponatremia. These aspects of renal physiology should be considered when antidiuretic drugs are prescribed for the treatment of nocturia.

  20. Adverse effects of oral corticosteroids in relation to dose in patients with lung disease

    PubMed Central

    Walsh, L; Wong, C; Oborne, J; Cooper, S; Lewis, S; Pringle, M; Hubbard, R; Tattersfield, A

    2001-01-01

    BACKGROUND—The adverse effects of oral corticosteroids are widely recognised but there are few quantitative data on which to base advice to patients. In a two part cross sectional study we compared adverse effects in patients with lung disease taking oral corticosteroids and control subjects and related the adverse effects to corticosteroid dose in the patient group.
METHODS—Data on oral corticosteroid use, lifestyle, fractures, and other possible adverse effects were collected by questionnaire and compared between a community based cohort of patients taking continuous or frequent intermittent oral corticosteroids for asthma, chronic obstructive pulmonary disease, or alveolitis and age and sex matched control subjects. Dose related effects were explored in the corticosteroid group using cumulative dose quartiles and multiple logistic regression.
RESULTS—A total of 367 patients (⩾50 years, 48% female) and 734 control subjects completed the questionnaire. The cumulative incidence of fractures since the time of diagnosis was 23% for patients taking oral corticosteroids and 15% in the control group (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.3 to 2.6). Patients were more likely to have had a fracture of the vertebrae (OR 10; 95% CI 2.9 to 34), hip (OR 6; 95% CI 1.2 to 30), and ribs or sternum (OR 3.2, 95% CI 1.6 to 6.6) than control subjects. They also reported a significant increase in cataracts, use of antacids, muscle weakness, back pain, bruising, oral candidiasis, and having fewer teeth. The effects of oral corticosteroids were dose related: the odds ratio for patients in the highest compared with the lowest cumulative dose quartile (median prednisolone dose 61 g versus 5 g) ranged from 2 for all fractures to 9 for vertebral fractures and bruising.
CONCLUSIONS—By quantifying the morbidity associated with the use of oral corticosteroids, this study should help to rationalise their long term use.

 PMID:11254818

  1. Effects of Polyphenols from Grape Seeds on Renal Lithiasis

    PubMed Central

    Grases, Felix; Prieto, Rafel M.; Fernandez-Cabot, Rafel A.; Costa-Bauzá, Antonia; Tur, Fernando; Torres, Jose Juan

    2015-01-01

    Nephrolithiasis is a complex disease that results from a combination of factors related to both urine composition and kidney morphoanatomy. Development of calcium oxalate monohydrate papillary calculi is linked to initial subepithelial calcification of renal papilla. Progressive tissue calcification depends on preexisting injury and involves reactive oxygen species. Many plant extracts that protect against oxidative stress manifest antilithiasic activity. Our study focused on determining the effects of polyphenols on a lithiasis rat model. Rats were pretreated with polyphenols and grape seed extracts, followed by posterior induction of hyperoxalosis via treatment with ethylene glycol plus NH4Cl. The concentrations of calcium and other elements in kidney were determined, along with histological examination of kidney and 24 h urine analysis. Significant differences were observed in the renal calcium content between the control plus ethylene glycol-treated group and the epicatechin plus ethylene glycol-treated, red grape seed extract plus ethylene glycol-treated, and white grape seed extract plus ethylene glycol-treated groups, with reductions of about 50%. The antioxidant activity of polyphenols extracted from red and white grape seeds may be critical in the prevention of calcium oxalate monohydrate papillary calculus formation, particularly if calculi are induced by lesions caused by cytotoxic compounds with oxidative capacity. PMID:25883748

  2. Effect of Shock Wave Lithotripsy on Renal Hemodynamics

    NASA Astrophysics Data System (ADS)

    Handa, Rajash K.; Willis, Lynn R.; Evan, Andrew P.; Connors, Bret A.

    2008-09-01

    Extracorporeal shock wave lithotripsy (SWL) can injure tissue and decrease blood flow in the SWL-treated kidney, both tissue and functional effects being largely localized to the region targeted with shock waves (SWs). A novel method of limiting SWL-induced tissue injury is to employ the "protection" protocol, where the kidney is pretreated with low-energy SWs prior to the application of a standard clinical dose of high-energy SWs. Resistive index measurements of renal vascular resistance/impedance to blood flow during SWL treatment protocols revealed that a standard clinical dose of high-energy SWs did not alter RI during SW application. However, there was an interaction between low- and high-energy SWL treatment phases of the "protection" protocol such that an increase in RI (vasoconstriction) was observed during the later half of SW application, a time when tissue damage is occurring during the standard high-energy SWL protocol. We suggest that renal vasoconstriction may be responsible for reducing the degree of tissue damage that normally results from a standard clinical dose of high-energy SWs.

  3. Effects and Side Effects of Using Sorafenib and Sunitinib in the Treatment of Metastatic Renal Cell Carcinoma

    PubMed Central

    Randrup Hansen, Caroline; Grimm, Daniela; Bauer, Johann; Wehland, Markus; Magnusson, Nils E.

    2017-01-01

    In recent years, targeted therapies have proven beneficial in terms of progression-free survival (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC). The tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib are included in international clinical guidelines as first-line and second-line therapy in mRCC. Hypertension is an adverse effect of these drugs and the degree of hypertension associates with the anti-tumour effect. Studies have compared newer targeted drugs to sorafenib and sunitinib in terms of PFS, OS, quality of life and safety profiles. Phase III studies presented promising response rates and acceptable safety profiles of axitinib and tivozanib compared to sorafenib, and a phase II study reported greater efficacy using a combination of bevacizumab and IFN-α compared to sunitinib. Treatment with nintedanib exhibited a notably low prevalence of hypertension compared to sunitinib. The use of sorafenib and sunitinib are challenged by new drugs, but do not appear likely to be substituted in the near future. To clarify whether newer targeted drugs should replace sorafenib and sunitinib, more research is needed. This manuscript reviews the current utility and adverse effects of sorafenib and sunitinib and newer targeted therapies in the treatment of mRCC. PMID:28230776

  4. Adverse health effects and unhealthy behaviors among medical students using Facebook.

    PubMed

    Al-Dubai, Sami Abdo Radman; Ganasegeran, Kurubaran; Al-Shagga, Mustafa Ahmed Mahdi; Yadav, Hematram; Arokiasamy, John T

    2013-01-01

    Little is known about the relationships between adverse health effects and unhealthy behaviors among medical students using Facebook. The aim of this study was to determine the associations between adverse health effects and unhealthy behaviors with Facebook use. A cross-sectional study was conducted in a private university in Malaysia among 316 medical students. A self-administered questionnaire was used. It included questions on sociodemographics, pattern of Facebook use, social relationship, unhealthy behaviors, and health effects. Mean age was 20.5 (±2.7) years. All students had a Facebook account. The average daily Facebook surfing hours were 2.5 (±1.7). Significant associations were found between average hours of Facebook surfing and the following factors: isolation from family members and community, refusing to answer calls, musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours spent on Facebook were significantly associated with holding urination and defecation while online, surfing Facebook until midnight, and postponing, forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook were associated with adverse health effects and unhealthy behaviors among medical students, as well as social isolation from the family and community.

  5. Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.

    PubMed

    El-Sayed, Wael M; Al-Kahtani, Mohamed Ali

    2011-09-01

    Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

  6. Evidence for adverse effect of perinatal glucocorticoid use on the developing brain

    PubMed Central

    2014-01-01

    The use of glucocorticoids (GCs) in the perinatal period is suspected of being associated with adverse effects on long-term neurodevelopmental outcomes for preterm infants. Repeated administration of antenatal GCs to mothers at risk of preterm birth may adversely affect fetal growth and head circumference. Fetal exposure to excess GCs during critical periods of brain development may profoundly modify the limbic system (primarily the hippocampus), resulting in long-term effects on cognition, behavior, memory, co-ordination of the autonomic nervous system, and regulation of the endocrine system later in adult life. Postnatal GC treatment for chronic lung disease in premature infants, particularly involving the use of dexamethasone, has been shown to induce neurodevelopmental impairment and increases the risk of cerebral palsy. In contrast to studies involving postnatal dexamethasone, long-term follow-up studies for hydrocortisone therapy have not revealed adverse effects on neurodevelopmental outcomes. In experimental studies on animals, GCs has been shown to impair neurogenesis, and induce neuronal apoptosis in the immature brains of newborn animals. A recent study has demonstrated that dexamethasone-induced hypomyelination may result from the apoptotic degeneration of oligodendrocyte progenitors in the immature brain. Thus, based on clinical and experimental studies, there is enough evidence to advice caution regarding the use of GCs in the perinatal period; and moreover, the potential long-term effects of GCs on brain development need to be determined. PMID:24778691

  7. The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects.

    PubMed

    van Amsterdam, Jan; Brunt, Tibor; van den Brink, Wim

    2015-03-01

    Cannabis use is associated with an increased risk of psychosis in vulnerable individuals. Cannabis containing high levels of the partial cannabinoid receptor subtype 1 (CB1) agonist tetrahydrocannabinol (THC) is associated with the induction of psychosis in susceptible subjects and with the development of schizophrenia, whereas the use of cannabis variants with relatively high levels of cannabidiol (CBD) is associated with fewer psychotic experiences. Synthetic cannabinoid receptor agonists (SCRAs) are full agonists and often more potent than THC. Moreover, in contrast to natural cannabis, SCRAs preparations contain no CBD so that these drugs may have a higher psychosis-inducing potential than cannabis. This paper reviews the general toxicity profile and the adverse effects of SCRAs with special emphasis on their psychosis-inducing risk. The review shows that, compared with the use of natural cannabis, the use of SCRAs may cause more frequent and more severe unwanted negative effects, especially in younger, inexperienced users. Psychosis and psychosis-like conditions seem to occur relatively often following the use of SCRAs, presumably due to their high potency and the absence of CBD in the preparations. Studies on the relative risk of SCRAs compared with natural cannabis to induce or evoke psychosis are urgently needed.

  8. Technical evaluation report, AGARD Fluid Dynamics Panel Symposium on Effects of Adverse Weather on Aerodynamics

    NASA Technical Reports Server (NTRS)

    Reinmann, J. J.

    1991-01-01

    The purpose of the meeting on Effects of Adverse Weather on Aerodynamics was to provide an update of the stae-of-the-art with respect to the prediction, simulation, and measurement of the effects of icing, anti-icing fluids, and various precipitation on the aerodynamic characteristics of flight vehicles. Sessions were devoted to introductory and survey papers and icing certification issues, to analytical and experimental simulation of ice frost contamination and its effects of aerodynamics, and to the effects of heavy rain and deicing/anti-icing fluids.

  9. Penicillamine revisited: historic overview and review of the clinical uses and cutaneous adverse effects.

    PubMed

    Ishak, Rim; Abbas, Ossama

    2013-06-01

    Penicillamine is a well-known heavy metal chelator, classically used in the treatment of Wilson disease, rheumatoid arthritis, and cystinuria. From a dermatologic standpoint, penicillamine was found to be useful in the treatment of systemic sclerosis. The successful therapeutic uses of penicillamine have been hindered by its numerous adverse effects, both cutaneous and extra-cutaneous. It is a unique drug since it provokes a diversity of dermatologic manifestations that include (1) acute hypersensitivity reactions, (2) dermopathies characterized by elastic fiber abnormalities including elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum, (3) autoimmune disorders such as pemphigus and penicillamine-induced lupus erythematosus-like syndrome, and (4) miscellaneous dermatoses that result from undefined mechanisms. These cutaneous adverse effects may correlate with the dosage and duration of penicillamine therapy as well as the disease being treated.

  10. Statistical Mining of Potential Drug Interaction Adverse Effects in FDA's Spontaneous Reporting System.

    PubMed

    Harpaz, Rave; Haerian, Krystl; Chase, Herbert S; Friedman, Carol

    2010-11-13

    Many adverse drug effects (ADEs) can be attributed to drug interactions. Spontaneous reporting systems (SRS) provide a rich opportunity to detect novel post-marketed drug interaction adverse effects (DIAEs), as they include populations not well represented in clinical trials. However, their identification in SRS is nontrivial. Most existing research have addressed the statistical issues used to test or verify DIAEs, but not their identification as part of a systematic large scale database-wide mining process as discussed in this work. This paper examines the application of a highly optimized and tailored implementation of the Apriori algorithm, as well as methods addressing data quality issues, to the identification of DIAEs in FDAs SRS.

  11. A Cohort Study on Long-Term Adverse Effects of Parental Drinking: Background and Study Design

    PubMed Central

    Lund, Ingunn Olea; Bukten, Anne; Storvoll, Elisabet E; Moan, Inger Synnøve; Skurtveit, Svetlana; Handal, Marte; Nordfjærn, Trond; Brunborg, Geir Scott; Rossow, Ingeborg

    2015-01-01

    Although many studies have addressed adverse outcomes in children of parents with alcohol abuse/dependence, less is known about the possible long-term effects of more normative patterns of parental alcohol consumption, including drinking at lower risk levels and heavy episodic or binge drinking. The extent of harm from parental drinking may therefore be underestimated. With this research proposal, we describe a project that aims to assess possible long-term adverse effects of parental drinking by combining survey and nationwide registry data. Advantages of a longitudinal general population cohort design include that it allows for detailed information on parental drinking through survey data and identification of possible negative long-term health and social outcomes from exposure to parental drinking 1–19 years after exposure through continuously updated nationwide registers. The rich information available from combining survey and registry data allows us to take into account important confounders, mediators, and moderators. PMID:26688663

  12. [Asthma and polyposis. Efficacy and adverse effect of endonasal ethmoidectomy. Results apropos of 70 patients].

    PubMed

    Korchia, D; Thomassin, J M; Doris, J M; Badier, M

    1992-01-01

    The authors report the efficacy and adverse effects of intranasal ethmoidectomy in 70 patients with asthma and persistent severe symptoms from nasosinal polyposis despite repeated prior treatment. The efficacy was defined according to the evolution of symptoms and endoscopic findings. Adverse effects were evaluated according to subjective clinical and therapeutic data in all 70 patients. In addition, 25 patients had complete pre and post-operative pulmonary function tests. The results confirm that intranasal micro-surgery does not increase the severity of asthma. On the other hand, no significant improvement in bronchial function was noted after ethmoidectomy. Finally, the authors emphasize the poorer results obtained in Widal's disease and the importance, after the failure of medical treatment, of using of sufficiently extensive surgical procedure in order to decrease the incidence of recurrences.

  13. Role of mitochondrial dysfunction in renal fibrosis promoted by hypochlorite-modified albumin in a remnant kidney model and protective effects of antioxidant peptide SS-31.

    PubMed

    Zhao, Hao; Liu, Yan-Jun; Liu, Zong-Rui; Tang, Dong-Dong; Chen, Xiao-Wen; Chen, Yi-Hua; Zhou, Ru-Ning; Chen, Si-Qi; Niu, Hong-Xin

    2017-03-18

    Oxidative stress aggravates renal fibrosis, a pathway involved in almost all forms of chronic kidney disease (CKD). However, the underlying mechanism involved in the pathogenesis of renal oxidative stress has not been completely elucidated. In this study, we explored the role and mechanism of hypochlorite-modified albumin (HOCl-alb) in mediating oxidative stress and fibrotic response in a remnant-kidney rat model. Five-sixths nephrectomy (5/6 NX) was performed on the rats and then the animals were randomly assigned to intravenous treatment with either vehicle alone, or HOCl-rat serum albumin (RSA) in the presence or absence of SS-31 (administered intraperitoneally). A sham-operation control group was set up concurrently. Compared with the control group, 5/6 NX animals displayed marked mitochondrial (mt) dysfunction, as evidenced by decrease of mitochondrial membrane potential (MMP), ATP production, mtDNA copy number alterations and manganese superoxide dismutase (MnSOD) activity, release of cytochrome C (Cyto C) from mitochondria to the cytoplasm, and increase of mitochondrial reactive oxygen species in renal tissues. They also displayed increased levels of HOCl-alb in both plasma and renal tissues. These changes were accompanied by accumulation of extracellular matrix, worsened proteinuria, deteriorated renal function, and a marked increase of macrophage infiltration along with up-regulation of monocyte chemoattractant protein (MCP)-1 and transforming growth factor (TGF)-β1 expression. HOCl-alb challenge further exacerbated the above biological effects in 5/6 NX animals, but these adverse effects were prevented by administration of SS-31, a mitochondrial targeted antioxidant peptide. These data suggest that accumulation of HOCl-alb may promote renal inflammation and fibrosis, probably related to mitochondrial oxidative stress and dysfunction and that the mitochondrial targeted peptide SS-31 might be a novel therapy for renal fibrosis and chronic renal failure

  14. In vitro effects of nanoparticles on renal cells

    PubMed Central

    L'Azou, Béatrice; Jorly, Joana; On, Dinhill; Sellier, Elisabeth; Moisan, Frédéric; Fleury-Feith, Jocelyne; Cambar, Jean; Brochard, Patrick; Ohayon-Courtès, Céline

    2008-01-01

    Background The ability of nanoparticles to cross the lung-blood barrier suggests that they may translocate to blood and to targets distant from their portal of entry. Nevertheless, nanotoxicity in organs has received little attention. The purpose of this study was to evaluate nanotoxicity in renal cells using in vitro models. Various carbon black (CB) (FW2–13 nm, Printex60-21 nm and LB101-95 nm) and titanium dioxide (TiO2-15 and TiO2-50 nm) nanoparticles were characterized on size by electron microscopy. We evaluated theirs effects on glomerular mesangial (IP15) and epithelial proximal tubular (LLC-PK1) renal cells, using light microscopy, WST-1 assay, immunofluorescence labeling and DCFH-DA for reactive oxygen species (ROS) assay. Results Nanoparticles induced a variety of cell responses. On both IP15 and LLC-PK1 cells, the smallest FW2 NP was found to be the most cytotoxic with classic dose-behavior. For the other NPs tested, different cytotoxic profiles were found, with LLC-PK1 cells being more sensitive than IP15 cells. Exposure to FW2 NPs, evidenced in our experiments as the most cytotoxic particle type, significantly enhanced production of ROS in both IP15 and LLC-PK1 cells. Immunofluorescence microscopy using latex beads indicated that depending on their size, the cells internalized particles, which accumulated in the cell cytoplasm. Additionally using transmission electronic microscope micrographs show nanoparticles inside the cells and trapped in vesicles. Conclusion The present data constitute the first step towards determining in vitro dose effect of manufactured CB and TiO2 NPs in renal cells. Cytotoxicological assays using epithelial tubular and glomerular mesangial cell lines rapidly provide information and demonstrated that NP materials exhibit varying degrees of cytotoxicity. It seems clear that in vitro cellular systems will need to be further developed, standardized and validated (relative to in vivo effects) in order to provide useful screening

  15. Effect of pentoxifylline on renal outcomes in chronic kidney disease patients: A systematic review and meta-analysis.

    PubMed

    Leporini, Christian; Pisano, Anna; Russo, Emilio; D'Arrigo, Graziella; de Sarro, Giovambattista; Coppolino, Giuseppe; Bolignano, Davide

    2016-05-01

    Chronic kidney disease (CKD) represents an important health problem worldwide and the search for new therapeutic approaches for retarding CKD progression is a timely issue. Recent evidence suggest that the anti-inflammatory and hemorrheologic drug Pentoxifylline (PTX), may produce favorable effects on kidney function. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to ascertain whether PTX derivatives, alone or in combination to other treatments, may be useful in slowing down disease progression in patients with diabetic or non-diabetic CKD. We found 26 studies (1518 subjects) matching our search criteria. Information on the effects of PTX on hard renal outcomes (doubling of serum creatinine or need for chronic dialysis) were lacking in all the reviewed trials. Conversely, PTX was effective in reducing proteinuria compared to control, a benefit that was more evident in patients with type-1 diabetes mellitus, higher proteinuria at baseline and early renal impairment. An improvement in renal function (eGFR/creatinine clearance) was observed particularly in patients with more advanced CKD stage and in studies with longer follow-up. Conversely, cumulative analyses did not reveal any evident reduction in urinary albumin excretion, even in diabetic patients. The use of PTX was relatively safe as most trials recorded only minor gastrointestinal adverse effects. Although these findings point at some reno-protective effects of PTX, there is no conclusive evidence proving the usefulness of this agent for improving renal outcomes in subjects with chronic kidney disease of various etiology. Future trials adequately powered and designed on hard clinical end-points are needed.

  16. Neurodevelopment in children with intrauterine growth restriction: adverse effects and interventions.

    PubMed

    Wang, Yan; Fu, Wei; Liu, Jing

    2016-01-01

    Intrauterine growth restriction (IUGR) is associated with higher rates of fetal, perinatal, and neonatal morbidity and mortality. The consequences of IUGR include short-term metabolic, hematological and thermal disturbances that lead to metabolic syndrome in children and adults. Additionally, IUGR severely affects short- and long-term fetal brain development and brain function (including motor, cognitive and executive function) and neurobehavior, especially neuropsychology. This review details the adverse effects of IUGR on fetal brain development and discusses intervention strategies.

  17. Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

    SciTech Connect

    Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark; Gentili, Fred; Heydarian, Mostafa; Tsao, May; Schwartz, Michael; Prooijen, Monique van; Millar, Barbara-Ann; Menard, Cynthia; Kulkarni, Abhaya V.; Laperriere, Norm; Zadeh, Gelareh

    2012-04-01

    Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; and trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.

  18. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect.

    PubMed

    Mathew, Thomas; Sarma, G R K; Nadig, Raghunandan; Varghese, Raji

    2012-04-15

    Somnambulism (sleepwalking) is a disorder of arousal that falls under "parasomnia" group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers. This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine.

  19. Tooth-Bleaching: A Review of the Efficacy and Adverse Effects of Various Tooth Whitening Products.

    PubMed

    Majeed, Abdul; Farooq, Imran; Grobler, Sias R; Rossouw, R J

    2015-12-01

    Tooth bleaching (whitening) is one of the most common and inexpensive method for treating discolouration of teeth. Dental aesthetics, especially tooth colour, is of great importance to majority of the people; and discolouration of even a single tooth can negatively influence the quality of life. Therefore, a review of the literature was carried out (limited to aesthetic tooth-bleaching) to provide a broad overview of the efficacy and adverse effects of various tooth whitening products on soft and hard oral tissues.

  20. Effect of chronic renal medullary nitric oxide inhibition on blood pressure.

    PubMed

    Mattson, D L; Lu, S; Nakanishi, K; Papanek, P E; Cowley, A W

    1994-05-01

    The effects of chronic nitric oxide inhibition in the renal medulla on renal cortical and medullary blood flow, sodium balance, and blood pressure were evaluated in conscious uninephrectomized Sprague-Dawley rats. During a 5-day renal medullary interstitial infusion of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 120 micrograms/h) in saline (0.5 ml/min), renal medullary blood flow was selectively decreased by 30% after 2 h and was maintained at that level for the entire infusion. The decrease in medullary blood flow was associated with sodium retention and increased blood pressure. After the cessation of L-NAME infusion, medullary blood flow returned to control, and the sodium balance became negative as blood pressure returned to baseline. These data indicate that renal medullary nitric oxide plays an important role in the regulation of renal blood flow, sodium excretion, and blood pressure.

  1. Possible adverse effect of chromium in occupational exposure of tannery workers.

    PubMed

    Kornhauser, Carlos; Wróbel, Katarzyna; Wróbel, Kazimierz; Malacara, Juan Manuel; Nava, Laura Eugenia; Gómez, Leobardo; González, Rita

    2002-04-01

    Our aim was to investigate the adverse effects of occupational exposure to trivalent chromium. We measured chromium and iron levels in serum and urine and hemoglobin levels in tannery workers and unexposed persons. We studied three groups of subjects. Group 1 included 15 non-smoking male tannery workers highly exposed to chromium from tanning and retanning departments. Group 2 included 14 non-smoking male tannery workers with moderate chromium exposure from dying, drying and finishing departments. Group 3 included 11 healthy, non-smoking male subjects without direct chromium exposure. Higher serum chromium levels were observed in groups 1 and 2 with respect to group 3 (mean values respectively: 0.43; 0.25 and 0.13 microg x l(-1)). Urine chromium levels in group 1 were higher than those in controls (mean values: 1.78 and 1.35 microg x l(-1)). In group 1 an inverse association was found between serum chromium and urine iron (-0.524), urine chromium and hemoglobin (-0.594) and between the urine chromium to iron ratio and hemoglobin (-0.693, p<0.05). The results suggest a chromium adverse effect on iron metabolism, possibly associated with excessive body chromium accumulation. In conclusion, chromium urine test could be recommended for diagnosis of chromium adverse effect on iron metabolism. Further studies are needed to quantify the relationship between urine chromium and hemoglobin metabolism.

  2. A strategy for regulatory action when new adverse effects of a licensed product emerge.

    PubMed

    Aronson, Jeffrey K; Price, Deirdre; Ferner, Robin E

    2009-01-01

    Regulatory agencies grant product licences (marketing authorizations) for medicinal products in the light of evidence that the balance between benefit and harm in the population is favourable. Here we consider a framework for allowing regulatory agencies to make rational decisions when reviewing product licences in the light of new information about harms that change that balance. The regulator can revoke the product licence, restrict the product's availability or change the 'label' in different ways. We examine the features of the adverse effect that may be relevant in making the decision: namely, individual differences in susceptibility; the possibility of monitoring; and the availability of protective strategies. The balance of benefit and harm, and the time-course and dose relation of the adverse effect play important roles in the decision-making process. We set out how these factors can help determine the logical response to new information on the balance between benefit and harm, and provide a series of relevant examples. We believe that when regulatory agencies have to decide how to amend the product licence of a drug when new serious adverse effects cause concern, they would find it useful to adopt a framework of this kind, using different strategies for different cases. Our proposed framework could also be useful in risk management planning during drug development.

  3. The Adverse Effect of Hypertension in the Treatment of Thyroid Cancer with Multi-Kinase Inhibitors

    PubMed Central

    Ancker, Ole Vincent; Wehland, Markus; Bauer, Johann; Infanger, Manfred; Grimm, Daniela

    2017-01-01

    The treatment of thyroid cancer has promising prospects, mostly through the use of surgical or radioactive iodine therapy. However, some thyroid cancers, such as progressive radioactive iodine-refractory differentiated thyroid carcinoma, are not remediable with conventional types of treatment. In these cases, a treatment regimen with multi-kinase inhibitors is advisable. Unfortunately, clinical trials have shown a large number of patients, treated with multi-kinase inhibitors, being adversely affected by hypertension. This means that treatment of thyroid cancer with multi-kinase inhibitors prolongs progression-free and overall survival of patients, but a large number of patients experience hypertension as an adverse effect of the treatment. Whether the prolonged lifetime is sufficient to develop sequelae from hypertension is unclear, but late-stage cancer patients often have additional diseases, which can be complicated by the presence of hypertension. Since the exact mechanisms of the rise of hypertension in these patients are still unknown, the only available strategy is treating the symptoms. More studies determining the pathogenesis of hypertension as a side effect to cancer treatment as well as outcomes of dose management of cancer drugs are necessary to improve future therapy options for hypertension as an adverse effect to cancer therapy with multi-kinase inhibitors. PMID:28335429

  4. Adverse events in 50 cats with allergic dermatitis receiving ciclosporin.

    PubMed

    Heinrich, Nicole A; McKeever, Patrick J; Eisenschenk, Melissa C

    2011-12-01

    Ciclosporin is an immunosuppressive drug that has been used to treat allergies and other immune-mediated diseases in cats, dogs and humans. Information about the adverse effects of ciclosporin in cats has been limited to smaller studies and case reports. Adverse effects in dogs are mainly gastrointestinal in nature, but humans can also experience hypertension and altered renal function. The aim of this retrospective case series study was to document the occurrence and clinical appearance of adverse events in cats receiving ciclosporin to treat allergic skin disease. The medical records of 50 cats with allergic dermatitis treated with oral ciclosporin (1.9-7.3 mg/kg/day) were reviewed. Adverse events occurred in 66% (33 cats). Adverse events likely to be associated with ciclosporin included the following: vomiting or diarrhoea within 1-8 weeks of receiving ciclosporin (24%), weight loss (16%), anorexia and subsequent hepatic lipidosis (2%) and gingival hyperplasia (2%). Other adverse events less likely to be associated with ciclosporin therapy included the following: weight gain (14%), dental tartar and gingivitis (10%), otitis (4%), chronic diarrhoea (4%), inflammatory bowel disease with indolent gastrointestinal lymphoma (2%), urinary tract infection (2%), cataract (2%), elevated liver enzymes (2%), hyperthyroidism and renal failure (2%) and transient inappropriate urination (2%). Some cats experienced multiple adverse events. Case-control studies are needed to prove cause and effect of ciclosporin with regard to these adverse events.

  5. Functional consequences of prenatal methylmercury exposure: effects on renal and hepatic responses to trophic stimuli and on renal excretory mechanisms

    SciTech Connect

    Slotkin, T.A.; Kavlock, R.J.; Cowdery, T.; Orband, L.; Bartolome, M.

    1986-01-01

    The effects of prenatal exposure to methylmercury on the functional development of renal and hepatic response systems was examined in the developing rat. Methylmercury produced an elevation of basal activity of renal ornithine decarboxylase (ODC, an enzyme involved in regulation of cellular maturation) and an eventual relative hypertrophy; liver ODC was reduced and hypertrophy was not evident. In contrast, the reactivity of liver ODC to trophic stimulants (vasopressin, isoproterenol) was markedly enhanced by prenatal methylmercury exposure, whereas renal ODC responses were much less affected (vasopressin) or actually reduced (isoproterenol). Targeted actions of methylmercury on renal excretory function were also prominent, with increased fractional excretions urea and electrolytes and an eventual reduction in glomerular filtration as assessed by creatinine clearance. These studies show that doses of methylmercury ordinarily associated with selective actions on development of neurobehavioral patterns also influence the functional ontogeny of other organ systems; furthermore, the fact that the target tissues are different for prenatal vs postnatal methylmercury exposure, indicates that the functional teratology of methylmercury exhibits critical periods of sensitivity.

  6. Effect of a stable prostacyclin analogue on canine renal allograft rejection.

    PubMed Central

    Tobimatsu, M; Ueda, Y; Toyoda, K; Saito, S; Konomi, K

    1987-01-01

    The effect of OP-41483 (Ono Pharmaceutical Co., Osaka, Japan), a stable prostacyclin analogue, on canine renal allograft rejection was investigated. Administration for 4 days after transplantation significantly increased renal cortical blood flow and urine output when compared with untreated dogs with renal allografts. Serum creatinine levels remained relatively low during postoperative days 1-4. Mean animal survival time was prolonged. Vascular lesions and mononuclear cell infiltration were greatly diminished in biopsy specimens removed on day 4. This stable prostacyclin analogue provided a degree of protection against canine renal allograft rejection. Images Figs. 1A and B. PMID:3545109

  7. Renal disease in pregnancy.

    PubMed

    Sanders, C L; Lucas, M J

    2001-09-01

    Women with renal disease who conceive and continue a pregnancy are at significant risk for adverse maternal and fetal outcomes. Risk is inversely related to the degree of renal insufficiency. Pregnancy-induced changes in the urinary tract can temporarily increase renal function compromise, such as nephrosis, but most often results in no net increase in dysfunction. Common complications of pregnancy--such as hypertension and hypovolemia--can be associated with acute renal injury or aggravation of pre-existing disease.

  8. Health-protective and Adverse Effects of the Apolipoprotein E ε2 Allele in Older Males

    PubMed Central

    Kulminski, Alexander M.; Ukraintseva, Svetlana V.; Arbeev, Konstantin G.; Manton, Kenneth G.; Oshima, Junko; Martin, George M.; Il'yasova, Dora; Yashin, Anatoli I.

    2009-01-01

    OBJECTIVES: To re-examine a health-protective role of the common Apolipoprotein E (APOE) polymorphism focusing on connections between the APOE ε2-containing genotypes and impairments in instrumental activities of daily living [IADL] in older (65+) males and females. To examine how these connections may be mediated by diagnosed coronary heart disease (CHD), Alzheimer's disease, colorectal cancer, macular degeneration (MD), and atherosclerosis. DESIGN: Retrospective cross-sectional study. SETTING: The unique disability-focused data from a genetic sub-sample of the 1999 National Long Term Care Survey linked with Medicare service use files. PARTICIPANTS: 1733 genotyped individuals interviewed on IADL disabilities. MEASUREMENTS: Indicators of IADL impairments, five geriatric disorders, and ε2-containing genotypes. RESULTS: The ε2/3 genotype is a major contributor to adverse associations between the ε2 allele and IADL disability in males [Odds Ratio (OR)=3.09, Confidence Interval (CI)=1.53-6.26)]. It shows, however, significant protective effects for CHD (OR=0.55, CI=0.33-0.92), while CHD is adversely associated with IADL disability (OR=2.18, CI=1.28-3.72). The presence of five diseases does not significantly alter the adverse association between ε2-containing genotypes and disability. Protective effects of the ε2/3 genotype for CHD (OR=0.52, CI=0.27-0.99) and deleterious effects for IADL (OR=3.50, CI=1.71-7.14) for males hold in multivariate models with both these factors included. No significant associations between the ε2-containing genotypes and IADL are found in females. CONCLUSIONS: The ε2 allele can play a dual role in males, protecting them against some health disorders, while promoting others. Strong adverse relationships with disability suggest that ε2-containing genotypes can be unfavorable factors for the health/well-being of aging males. PMID:18179501

  9. Second-generation antipsychotics: is there evidence for sex differences in pharmacokinetic and adverse effect profiles?

    PubMed

    Aichhorn, Wolfgang; Whitworth, Alexandra B; Weiss, Elisabeth M; Marksteiner, Josef

    2006-01-01

    Six second-generation antipsychotics (SGAs), aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone, are currently US FDA approved. The aim of this review is to investigate whether sex differences exist for efficacy and adverse effects of these drugs.Sex-related differences have been shown in the pharmacokinetics of cytochrome P450 (CYP), with a higher activity in females for CYP3A4 and CYP2D6. However, even if there are pharmacokinetic differences between females and males, significantly higher plasma concentrations in women have been demonstrated only for olanzapine and clozapine. To date, sex differences in adverse effects have not been well studied, but some adverse effects such as weight gain, hyperprolactinaemia and cardiac effects are reported to be particularly problematic for women. Most of the studies reviewed indicate that clozapine and olanzapine are associated with greater bodyweight gain than the other atypical antipsychotics, and that serious adverse effects such as metabolic syndrome, which includes increased visceral adiposity, hyperglycaemia, hypertension and dyslipidaemia induced by SGAs, are more frequent in females. According to most studies, the risk for cardiac adverse effects induced by SGAs is the same in male and female patients. Although women are at a lower risk of sudden cardiac death, they have a higher risk of induced long QT syndrome from antiarrhythmic and, probably, antipsychotic drugs. The propensity of sexual dysfunctions is higher with conventional antipsychotics than with SGAs. Additionally, there is some evidence that female sexual dysfunction is associated with high prolactin levels; however, whether the degree of prolactin level elevation is different between female and male patients remains controversial. There is no evidence for sex differences for any of the SGAs to cause a higher rate of extrapyramidal symptoms, acute dystonia or any other movement disturbance. Knowledge of the risks and benefits

  10. Effects of a high protein intake on renal acid excretion in bodybuilders.

    PubMed

    Manz, F; Remer, T; Decher-Spliethoff, E; Höhler, M; Kersting, M; Kunz, C; Lausen, B

    1995-03-01

    Bodybuilders often prefer a high protein diet to achieve maximum skeletal muscle hypertrophy. In this study the effect of a high protein diet on renal acid load and renal handling of proton excretion was studied comparing dietary intake and urinary ionograms in 37 male bodybuilders and 20 young male adults. Energy intake (+ 7%), protein intake (128 vs 88 g/d/1.73 m2), and renal net acid excretion (95 vs 64 mmol/d/1.73 m2) were higher in the bodybuilders than in the controls, however, urine-pH was only slightly lower (5.83 vs 6.12). In the bodybuilders renal ammonium excretion was higher at any given value of urine pH than in the controls. In a regression analysis protein intake proved to be an independent factor modulating the ratio between urine-pH and renal ammonium excretion. The concomitant increase of renal net acid excretion and maximum renal acid excretion capacity in periods of high protein intake appears to be a highly effective response of the kidney to a specific food intake leaving a large renal surplus capacity for an additional renal acid load.

  11. The effect of MMF dose and trough levels on adverse effects in pediatric heart transplant recipients.

    PubMed

    Siddiqi, Nida; Lamour, Jacqueline M; Hsu, Daphne T

    2015-09-01

    Limited pharmacokinetic and safety data exist for MMF in pediatric HTR. Previously targeted MPA-TL are 1.5-3.0 μg/mL. The objective of this study was to assess the outcomes targeting MPA-TL of 0.8-2.0 μg/mL in pediatric HTR. MPA-TL were retrospectively collected 2-12 months post-transplant. Acute rejection, infection, leukopenia, and GI complaints were then correlated with MPA-TL. A total of 355 MPA-TL from 22 HTR were included. Median age was 2.5 yr. Primary indication for transplant was dilated cardiomyopathy (64%). Mean MPA-TL was 1.7 ± 0.9 μg/mL. African American patients received significantly higher doses (702 ± 235 mg/m(2) ) compared with other races (p = 0.035). Leukopenia was less common in patients with SUB MPA vs. others (p = 0.01). MMF was discontinued for GI complaints in one patient and leukopenia in two patients. One SUB patient had acute rejection, and one SUP patient had infection. One-yr survival was 100%. Targeting a lower range for MPA-TL was not associated with significant rejection or infection. Despite lower MPA-TL, MMF was discontinued in 3/22 patients for adverse effects.

  12. The Ginkgo biloba Extract Reverses the Renal Effects of Titanium Dioxide Nanoparticles in Adult Male Rats

    PubMed Central

    Reynoso-Andeola, Irma Guadalupe; Jaramillo-Juárez, Fernando; Martínez-Ruvalcaba, Haydée; Posadas del Rio, Francisco A.

    2016-01-01

    The Ginkgo biloba extract (GbE) is a commercial product used as a nutraceutic herbal remedy in Europe and US. It contains 27% of the polyphenols isorhamnetin, kaempferol, and quercetin, as antioxidants. We used male adult Wistar rats (200–300 g), divided into four groups: control group (treated with 5.0 mg/kg of sodium chloride, intravenous), titanium dioxide nanoparticles (TiO2-NPs) group (5.0 mg/kg, intravenous), GbE group (10 mg/kg, intraperitoneal), and GbE + TiO2-NPs group (treated 24 h before with 10 mg/kg of GbE, intraperitoneal), followed, 24 h later, by 5.0 mg/kg of TiO2-NPs intravenously. The statistical analysis was performed using Student's t-test for grouped data with ANOVA posttest. The GbE protected renal cells against the effects of TiO2-NPs because it reversed the increased activity of γ-glutamyltranspeptidase and the enzymatic activity of dipeptidylaminopeptidase IV at all times tested (0–5, 5–24, 24–48, and 48–72 h). Also it reversed the glucosuria, hypernatriuria, and urine osmolarity at three times tested (5–24, 24–48, and 48–72). Thus, we conclude that GbE has a beneficial activity in the cytoplasmic membranes of brush border cells on the renal tubules, against the adverse effects that can be produced by some xenobiotics in this case the TiO2-NPs, in experimental rats. PMID:27042354

  13. Adverse Drug Effects and Preoperative Medication Factors Related to Perioperative Low-Dose Ketamine Infusions.

    PubMed

    Schwenk, Eric S; Goldberg, Stephen F; Patel, Ronak D; Zhou, Jon; Adams, Douglas R; Baratta, Jaime L; Viscusi, Eugene R; Epstein, Richard H

    2016-01-01

    High-dose opioid administration is associated with significant adverse events. Evidence suggests that low-dose ketamine infusions improve perioperative analgesia over conventional opioid management, but usage is highly variable. Ketamine's adverse drug effects (ADEs) are well known, but their prevalence during low-dose infusions in a clinical setting and how often they lead to infusion discontinuation are unknown. The purposes of this study were 3-fold: (1) to identify patient factors associated with initiation of ketamine infusions during spine surgery, (2) to identify specific spine procedures in which ketamine has been used most frequently, and (3) to identify ADEs associated with postoperative ketamine infusions and which ADEs most frequently led to discontinuation. Spine surgery was chosen because of its association with moderate to severe pain and a relatively high use of ketamine infusions in this population at our hospital.

  14. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects.

    PubMed

    Streissguth, Ann P; Bookstein, Fred L; Barr, Helen M; Sampson, Paul D; O'Malley, Kieran; Young, Julia Kogan

    2004-08-01

    Clinical descriptions of patients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) suggest major problems with adaptive behavior. Five operationally defined adverse outcomes and 18 associated risk/protective factors were examined using a Life History Interview with knowledgeable informants of 415 patients with FAS or FAE (median age 14 years, range 6-51; median IQ 86, range 29-126). Eighty percent of these patients were not raised by their biological mothers. For adolescents and adults, the life span prevalence was 61% for Disrupted School Experiences, 60% for Trouble with the Law, 50% for Confinement (in detention, jail, prison, or a psychiatric or alcohol/drug inpatient setting), 49% for Inappropriate Sexual Behaviors on repeated occasions, and 35% for Alcohol/Drug Problems. The odds of escaping these adverse life outcomes are increased 2- to 4-fold by receiving the diagnosis of FAS or FAE at an earlier age and by being reared in good stable environments.

  15. Undesirable and adverse effects of tooth-whitening products: a review.

    PubMed

    Goldberg, Michel; Grootveld, Martin; Lynch, Edward

    2010-02-01

    Hydrogen peroxide (H(2)O(2)) is a powerful oxidising agent. It gives rise to agents known to be effective bleaching agents. The mechanisms of bleaching involve the degradation of the extracellular matrix and oxidation of chromophores located within enamel and dentin. However, H(2)O(2) produces also local undesirable effects on tooth structures and oral mucosa. In clinical conditions, the daily low-level doses used to produce tooth whitening never generate general acute and sub-acute toxic effects. Genotoxicity and carcinogenicity only occur at concentrations that are never reached during dental treatments. Some transient adverse effects have been reported on the oral mucosa and the digestive tract if the product is swallowed. Local effects may occur on the oral mucosa and dental tissues during whitening, namely, pulp sensitivity, cervical resorption, release of selected components of dental restorative materials, and alteration of the enamel surface. Most of the local effects are dependent of the technique and concentration of the product so far used, but as the results of bleaching obtained are not stable, repeated treatments add to the adverse effects. The informed decision to administer or not and the control of bleaching effects should stand in the hand of dental surgeons and certainly not as it appears at present, as cosmetics sold without any restriction despite the potential health hazards of peroxides.

  16. Sedimentary selenium as a causal factor for adverse biological effects: Toxicity thresholds and stream modeling

    SciTech Connect

    Va Derveer, W.; Canton, S.

    1995-12-31

    Selenium (Se) in the aquatic environment exhibits a strong association with particulate organic matter and as a result, measurements of waterborne concentration can be an unreliable predictor of bioaccumulation and adverse effects. Particulate-bound Se, typically measured as sedimentary Se, has been repeatedly implicated as a causal factor for Se bioaccumulation and subsequent potential for reproductive failures in fish and/or birds at sites receiving coal-fired power plant and refinery effluents as well as irrigation drainage. In fact, the premise that adverse biological effects are largely induced by sedimentary Se satisfies all of Hill`s criteria for a causal association. Despite these findings, most efforts to control Se continue to focus on waterborne concentrations because sedimentary toxicity thresholds are largely unknown. Sedimentary Se and associated biological effects data from studies of Se-bearing industrial effluent and irrigation drainage were compiled to initiate development of biological effects thresholds, The probability of adverse effects on fish or birds appears to be low up to a sedimentary Se concentration of about 2.8 {micro}g/g dry weight and high at 6.4 {micro}g/g dry weight (10th and 50th percentile of effects data, respectively). In addition, a preliminary regression model was derived for predicting dissolved to sedimentary Se transfer in streams as an interactive function of site-specific sedimentary organic carbon content (R{sup 2} = 0,870, p < 0.001) based on irrigation drainage studies in Colorado. This dissolved Se interaction with sedimentary organic carbon provides a possible explanation for the variable biological response to waterborne Se-organic-rich sites are predisposed to greater Se bioaccumulation and subsequent biological effects than organic-poor sites.

  17. Potential adverse effects of amphetamine treatment on brain and behavior: a review.

    PubMed

    Berman, S M; Kuczenski, R; McCracken, J T; London, E D

    2009-02-01

    Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central toxicity and adverse

  18. Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

    PubMed Central

    DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H.; Caudill, Jonathan W.; Trulson, Chad R.; Baglivio, Michael T.

    2017-01-01

    Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered. PMID:28327508

  19. Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

    PubMed

    DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H; Caudill, Jonathan W; Trulson, Chad R; Baglivio, Michael T

    2017-03-22

    Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered.

  20. Renal Handling of Circulating and Renal-Synthesized Hepcidin and Its Protective Effects against Hemoglobin-Mediated Kidney Injury.

    PubMed

    van Swelm, Rachel P L; Wetzels, Jack F M; Verweij, Vivienne G M; Laarakkers, Coby M M; Pertijs, Jeanne C L M; van der Wijst, Jenny; Thévenod, Frank; Masereeuw, Rosalinde; Swinkels, Dorine W

    2016-09-01

    Urinary hepcidin may have protective effects against AKI. However, renal handling and the potential protective mechanisms of hepcidin are not fully understood. By measuring hepcidin levels in plasma and urine using mass spectrometry and the kidney using immunohistochemistry after intraperitoneal administration of human hepcidin-25 (hhep25) in C57Bl/6N mice, we showed that circulating hepcidin is filtered by the glomerulus and degraded to smaller isoforms detected in urine but not plasma. Moreover, hepcidin colocalized with the endocytic receptor megalin in proximal tubules, and compared with wild-type mice, megalin-deficient mice showed higher urinary excretion of injected hhep25 and no hepcidin staining in proximal tubules that lack megalin. This indicates that hepcidin is reaborbed in the proximal tubules by megalin dependent endocytosis. Administration of hhep25 concomitant with or 4 hours after a single intravenous dose of hemoglobin abolished hemoglobin-induced upregulation of urinary kidney injury markers (NGAL and KIM-1) and renal Interleukin-6 and Ngal mRNA observed 24 hours after administration but did not affect renal ferroportin expression at this point. Notably, coadministration of hhep25 and hemoglobin but not administration of either alone greatly increased renal mRNA expression of hepcidin-encoding Hamp1 and hepcidin staining in distal tubules. These findings suggest a role for locally synthesized hepcidin in renal protection. Our observations did not support a role for ferroportin in hhep25-mediated protection against hemoglobin-induced early injury, but other mechanisms of cellular iron handling may be involved. In conclusion, our data suggest that both systemically delivered and locally produced hepcidin protect against hemoglobin-induced AKI.

  1. Parent Report of Antidepressant, Anxiolytic, and Antipsychotic Medication Use in Individuals with Williams Syndrome: Effectiveness and Adverse Effects

    ERIC Educational Resources Information Center

    Martens, Marilee A.; Seyfer, Daisha L.; Andridge, Rebecca R.; Foster, Jessica E. A.; Chowdhury, Monali; McClure, Kelsey E.; Coury, Daniel L.

    2012-01-01

    Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage…

  2. Effects of combined carotid chemoreceptor and atrial receptor stimulation on renal blood flow in anaesthetized dogs.

    PubMed Central

    Kappagoda, C T; Karim, F; Mackay, D

    1983-01-01

    In dogs anaesthetized with chloralose and artificially ventilated, carotid chemoreceptors were stimulated by changing the perfusate of the vascularly isolated carotid bifurcations from arterial to venous blood. Left atrial receptors were stimulated by distending balloons in two pulmonary vein-left atrial junctions and in this left atrial appendage. The left renal blood flow was measured by an electromagnetic flow meter at a constant systemic (renal) arterial pressure in preparations in which heart rate changes were prevented by administration of propranolol hydrochloride (0.5 mg kg-1) and atropine sulphate (0.4 mg kg-1). Muscular movement was prevented by gallamine triethiodide (0.2 mg kg-1). Stimulation of left atrial receptors resulted in a significant increase (P less than 0.001) in renal blood flow of 5.6 +/- 0.88 ml min-1 100 g-1 renal mass from a control of 223 ml min-1 100 g-1 renal mass. The responses were abolished by cooling the cervical vagus nerves to 6-8 degrees C. Stimulation of carotid chemoreceptors, by perfusion of the carotid bifurcations by venous blood, caused a decrease in renal blood flow of 20 +/- 6.9 ml min-1 100 g-1 renal mass from 224 ml min-1 100 g-1 renal mass. Stimulation of left atrial receptors during venous perfusion of carotid chemoreceptors resulted in an increase in renal blood flow of 10.9 +/- 1.82 ml min-1 100 g-1 renal mass from 208 ml min-1 100 g-1 renal mass. These results show that atrial receptors and chemoreceptors can interact in their effects on renal blood flow. PMID:6410054

  3. Inhaled diesel emissions generated with cerium oxide nanoparticle fuel additive induce adverse pulmonary and systemic effects.

    PubMed

    Snow, Samantha J; McGee, John; Miller, Desinia B; Bass, Virginia; Schladweiler, Mette C; Thomas, Ronald F; Krantz, Todd; King, Charly; Ledbetter, Allen D; Richards, Judy; Weinstein, Jason P; Conner, Teri; Willis, Robert; Linak, William P; Nash, David; Wood, Charles E; Elmore, Susan A; Morrison, James P; Johnson, Crystal L; Gilmour, Matthew Ian; Kodavanti, Urmila P

    2014-12-01

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe.

  4. Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

    PubMed Central

    Snow, Samantha J.; McGee, John; Miller, Desinia B.; Bass, Virginia; Schladweiler, Mette C.; Thomas, Ronald F.; Krantz, Todd; King, Charly; Ledbetter, Allen D.; Richards, Judy; Weinstein, Jason P.; Conner, Teri; Willis, Robert; Linak, William P.; Nash, David; Wood, Charles E.; Elmore, Susan A.; Morrison, James P.; Johnson, Crystal L.; Gilmour, Matthew Ian; Kodavanti, Urmila P.

    2014-01-01

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe. PMID:25239632

  5. [Renoprotective effects of statins under the conditions of acute renal failure, caused by rhabdomyolysis].

    PubMed

    Zamorskiĭ, I I; Zeleniuk, V G

    2014-01-01

    The experiment on white rats was targeted at the examination of influence of statins (atorvastatin, lovastatin, simvastatin) under the conditions of acute renal failure, caused by rhabdomyolysis. Renoprotective effects of statins were demonstrated by reduction of hyperazotemia and proteinuria and improvement of renal excretory function, which correlated with antioxidant properties of drugs.

  6. Effect of inhibition of converting enzyme on renal hemodynamics and sodium management in polycystic kidney disease.

    PubMed

    Torres, V E; Wilson, D M; Burnett, J C; Johnson, C M; Offord, K P

    1991-10-01

    We compared the tubular transport of sodium and the erythrocyte sodium-lithium countertransport activity in hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) and in normotensive control subjects. In addition, we assessed the effects of inhibition of converting enzyme on renal hemodynamics and sodium excretion in hypertensive patients with ADPKD to provide information on mechanisms responsible for the increased renal vascular resistance and filtration fraction and the adjustment of the pressure-natriuresis relationship during saline expansion, observed in patients with ADPKD, hypertension, and preserved renal function. In comparison with normotensive control subjects, the hypertensive patients with ADPKD had lower renal plasma flows, higher renal vascular resistances and filtration fractions, and similar proximal and distal fractional reabsorptions of sodium. The administration of enalapril resulted in significant increases in the renal plasma flow and significant reductions in mean arterial pressure, renal vascular resistance, and filtration fraction, but the glomerular filtration rate remained unchanged. Despite the significant reduction in mean arterial pressure during inhibition of converting enzyme, the distal fractional reabsorption of sodium decreased while the total fractional excretion of sodium remained unchanged or increased slightly. No significant differences were detected between the normotensive control subjects and the hypertensive patients with ADPKD in erythrocyte sodium-lithium countertransport activity, plasma renin activity, plasma aldosterone concentration, or atrial natriuretic factor. These results suggest that the renal renin-angiotensin system plays a central role in the alterations in renal hemodynamics and sodium management associated with the development of hypertension in ADPKD.

  7. Scientific and Regulatory Policy Committee: Recommended ("Best") Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies.

    PubMed

    Kerlin, Roy; Bolon, Brad; Burkhardt, John; Francke, Sabine; Greaves, Peter; Meador, Vince; Popp, James

    2016-02-01

    Recommendations (best practices) are provided by the Society of Toxicologic Pathology's Adversity Working Group for making consistent interpretations of test article-related effects as "adverse" and assigning a "no observed adverse effect level" (NOAEL) in nonclinical toxicity studies. Adverse is a term indicating "harm" to the test animal, while nonadverse indicates lack of harm. Adverse findings in the study reports should be defined in relation to effects on the test species used and within the context of the given study. Test article-related effects should be described on their own merits, and decisions to consider them as adverse or nonadverse should be justified. Related effects may be discussed together; in particular, markers of toxicity that are not in and of themselves adverse ideally should be discussed in conjunction with the causal toxicity to determine adversity. Adverse findings should be identified in subreports (clinical data, pathology data, etc.) if sufficient information is available, and/or in the final study report as individual or grouped findings, but study NOAELs should be established at the level of the overall study report. Interpretations such as "not biologically relevant" or "not toxicologically important" should be avoided unless defined and supported by scientific rationale. Decisions defining adverse findings and the NOAEL in final study reports should combine the expertise of all contributing scientific disciplines. Where possible, use of NOAELs in data tables should be linked to explanatory text that places them in context. Ideally, in nonclinical summary documents, NOAELs from multiple studies are considered together in defining the most important adverse responses in the most sensitive species. These responses are then considered along with an understanding of their likely mechanisms, as well as other information such as variability in species sensitivity, comparative pathology, reversibility and progression, kinetics, and

  8. Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts.

    PubMed

    Pernodet, Nadine; Fang, Xiaohua; Sun, Yuan; Bakhtina, Asya; Ramakrishnan, Aditi; Sokolov, Jonathan; Ulman, Abraham; Rafailovich, Miriam

    2006-06-01

    Nanoscale engineering is one of the most dynamically growing areas at the interface between electronics, physics, biology, and medicine. As there are no safety regulations yet, concerns about future health problems are rising. We investigated the effects of citrate/gold nanoparticles at different concentrations and exposure times on human dermal fibroblasts. We found that, as a result of intracellular nanoparticle presence, actin stress fibers disappeared, thereby inducing major adverse effects on cell viability. Thus, properties such as cell spreading and adhesion, cell growth, and protein synthesis to form the extracellular matrix were altered dramatically. These results suggest that the internal cell activities have been damaged.

  9. The effect of adverse information and positive promotion on women's preferences for prescribed contraceptive products.

    PubMed

    Knox, Stephanie A; Viney, Rosalie C; Gu, Yuanyuan; Hole, Arne R; Fiebig, Denzil G; Street, Deborah J; Haas, Marion R; Weisberg, Edith; Bateson, Deborah

    2013-04-01

    Recent rapid growth in the range of contraceptive products has given women more choice, but also adds complexity to the resultant decision of which product to choose. This paper uses a discrete choice experiment (DCE) to investigate the effect of adverse information and positive promotion on women's stated preferences for prescribed contraceptive products. In November 2007, 527 Australian women aged 18-49 years were recruited from an online panel. Each was randomly allocated to one of three information conditions. The control group only received basic information on contraceptive products. One treatment group also received adverse information on the risks of the combined oral pill. The other group received basic information and promotional material on the vaginal ring, newly introduced into Australia and on the transdermal patch, which is unavailable in Australia. Respondents completed 32 choice sets with 3 product options where each option was described by a product label: either combined pill, minipill, injection, implant, hormonal IUD, hormonal vaginal ring, hormonal transdermal patch or copper IUD; and by the attributes: effect on acne, effect on weight, frequency of administration, contraceptive effectiveness, doctor's recommendation, effect on periods and cost. Women's choices were analysed using a generalized multinomial logit model (G-MNL) and model estimates were used to predict product shares for each information condition. The predictions indicated that adverse information did not affect women's preferences for products relative to only receiving basic information. The promotional material increased women's preferences for the transdermal patch. Women in all groups had a low preference for the vaginal ring which was not improved by promotion. The findings highlight the need for researchers to pay attention to setting the context when conducting DCEs as this can significantly affect results.

  10. Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review

    PubMed Central

    Hirshburg, Jason M.; Kelsey, Petra A.; Therrien, Chelsea A.; Gavino, A. Carlo; Reichenberg, Jason S.

    2016-01-01

    Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment. PMID:27672412

  11. Renal and blood pressure effects from environmental cadmium exposure in Thai children

    SciTech Connect

    Swaddiwudhipong, Witaya; Mahasakpan, Pranee; Jeekeeree, Wanpen; Funkhiew, Thippawan; Sanjum, Rungaroon; Apiwatpaiboon, Thitikarn; Phopueng, Ittipol

    2015-01-15

    Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of β{sub 2}-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥1 μg/g creatinine. The prevalence of urinary cadmium ≥1 μg/g creatinine was significantly higher in girls and in those consuming rice grown in cadmium-contaminated areas. The geometric mean levels of urinary β{sub 2}-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary β{sub 2}-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children. - Highlights: • Few studies show renal effects from environmental cadmium exposure in children. • We report renal and blood pressure effects from cadmium exposure in Thai children. • Urinary β{sub 2}-microglobulin and calcium increased with increasing urinary cadmium. • The study found no association between urinary cadmium levels and blood pressure. • Environmental cadmium exposure can affect renal functions in children.

  12. Protective effect of Urtica dioica L. on renal ischemia/reperfusion injury in rat.

    PubMed

    Sayhan, Mustafa Burak; Kanter, Mehmet; Oguz, Serhat; Erboga, Mustafa

    2012-12-01

    Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. This study was designed to investigate the effect of Urtica dioica L. (UD), in I/R induced renal injury. A total of 32 male Sprague-Dawley rats were divided into four groups: control, UD alone, I/R and I/R + UD; each group contain 8 animals. A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. In the UD group, 3 days before I/R, UD (2 ml/kg/day intraperitoneal) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and kidney tissues samples were obtained for histopathological investigation in all groups. To date, no more histopathological changes on intestinal I/R injury in rats by UD treatment have been reported. Renal I/R caused severe histopathological injury including tubular damage, atrophy dilatation, loss of brush border and hydropic epithelial cell degenerations, renal corpuscle atrophy, glomerular shrinkage, markedly focal mononuclear cell infiltrations in the kidney. UD treatment significantly attenuated the severity of intestinal I/R injury and significantly lowered tubulointerstitial damage score than the I/R group. The number of PCNA and TUNEL positive cells in the control and UD alone groups was negligible. When kidney sections were PCNA and TUNEL stained, there was a clear increase in the number of positive cells in the I/R group rats in the renal cortical tissues. However, there is a significant reduction in the activity of PCNA and TUNEL in kidney tissue of renal injury induced by renal I/R with UD therapy. Our results suggest that administration of UD attenuates renal I/R injury. These results suggest that UD treatment has a protective effect against renal damage induced by renal I/R. This protective effect is possibly due to its ability to inhibit I/R induced renal damage, apoptosis and cell proliferation.

  13. Protective Effects of Luteolin on Lipopolysaccharide-Induced Acute Renal Injury in Mice

    PubMed Central

    Xin, Shao-bin; Yan, Hao; Ma, Jing; Sun, Qiang; Shen, Li

    2016-01-01

    Background Sepsis can cause serious acute kidney injury in bacterium-infected patients, especially in intensive care patients. Luteolin, a bioactive flavonoid, has renal protection and anti-inflammatory effects. This study aimed to investigate the effect and underlying mechanism of luteolin in attenuating lipopolysaccharide (LPS)-induced renal injury. Material/Methods ICR mice were treated with LPS (25 mg/kg) with or without luteolin pre-treatment (40 mg/kg for three days). The renal function, histological changes, degree of oxidative stress, and tubular apoptosis in these mice were examined. The effects of luteolin on LPS-induced expression of renal tumor necrosis factor-α (TNF-α), NF-κB, MCP-1, ICAM-1, and cleaved caspase-3 were evaluated. Results LPS resulted in rapid renal damage of mice, increased level of blood urea nitrogen (BUN), and serum creatinine (Scr), tubular necrosis, and increased oxidative stress, whereas luteolin pre-treatment could attenuate this renal damage and improve the renal functions significantly. Treatment with LPS increased TNF-α, NF-κB, IL-1β, cleaved caspase-3, MCP-1, and ICAM-1 expression, while these disturbed expressions were reversed by luteolin pre-treatment. Conclusions These results indicate that luteolin ameliorates LPS-mediated nephrotoxicity via improving renal oxidant status, decreasing NF-κB activation and inflammatory and apoptosis factors, and then disturbing the expression of apoptosis-related proteins. PMID:28029146

  14. Use of urinary renal biomarkers to evaluate the nephrotoxic effects of melamine or cyanuric acid in non-pregnant and pregnant rats.

    PubMed

    Bandele, O J; Stine, C B; Ferguson, M; Black, T; Olejnik, N; Keltner, Z; Evans, E R; Crosby, T C; Reimschuessel, R; Sprando, R L

    2014-12-01

    Although traditional assessments of renal damage detect loss of kidney function, urinary renal biomarkers are proposed to indicate early changes in renal integrity. The recent adulteration of infant formula and other milk-based foods with melamine revealed a link between melamine ingestion and nephropathy. Thus, the effects of melamine and related analogs (e.g., cyanuric acid) should be assessed in other potentially sensitive groups. We evaluated whether urinary Kim-1, clusterin, and osteopontin could detect the effects of high doses of melamine or cyanuric acid in pregnant and non-pregnant female rats gavaged with 1000 mg/kg bw/day for 10 days. We demonstrate that these biomarkers can differentiate the severity of effects induced by melamine or cyanuric acid. All melamine-treated animals experienced adverse effects; however, pregnant rats were most sensitive as indicated by increased SCr, BUN, and kidney weights, decreased body weight, and presence of renal crystals. These effects coincided with elevated urinary biomarker levels as early as day 2 of exposure. One cyanuric acid-treated rat displayed effects similar to melamine, including increased urinary biomarker levels. This work illustrates that these biomarkers can detect early effects of melamine or cyanuric acid crystal-induced nephropathy and further supports the use of urinary protein immunoassays as a powerful, non-invasive method to assess nephrotoxicity.

  15. Safety Profile of Finasteride: Distribution of Adverse Effects According to Structural and Informational Dichotomies of the Mind/Brain.

    PubMed

    Motofei, Ion G; Rowland, David L; Manea, Mirela; Georgescu, Simona R; Păunică, Ioana; Sinescu, Ioanel

    2017-02-04

    Finasteride is currently used extensively for male androgenic alopecia and benign prostatic hyperplasia; however, some adverse effects are severe and even persistent after treatment cessation, the so-called 'post-finasteride syndrome'. The following most severe adverse effects-sexual dysfunction and depression-often occur together and may potentiate one other, a fact that could explain (at least in part) the magnitude and persistence of finasteride adverse effects. This paper presents the pharmacological action of finasteride and the corresponding adverse effects, the biological base explaining the occurrence, persistence and distribution of these adverse effects, and a possible therapeutic solution for post-finasteride syndrome. The distribution of finasteride adverse effects is presented within a comprehensive and modern neuro-endocrine perspective related to structural and informational dichotomies of the brain. Understanding the variation of finasteride side effects among different populations would be necessary not only to delineate the safety profile of finasteride for different subgroups of men (a subject may or may not be affected by a certain anti-hormonal compound dependent on the individual neuro-endocrine profile), but also as a possible premise for a therapeutic approach of finasteride adverse effects. Such therapeutic approach should include administration of exogenous hormones, which are deficient in men with post-finasteride syndrome, namely dihydrotestosterone (in right-handed men) or progesterone/dihydroprogesterone (in left-handed subjects).

  16. Efficacy of Rasayana Avaleha as adjuvant to radiotherapy and chemotherapy in reducing adverse effects

    PubMed Central

    Vyas, Purvi; Thakar, A. B.; Baghel, M. S.; Sisodia, Arvind; Deole, Yogesh

    2010-01-01

    Cancer is the most dreadful disease affecting mankind. The available treatments such as chemotherapy and radiotherapy have cytotoxic effects, which are hazardous to the normal cells of the patient, causing many unnecessary effects. This further leads to complications of the therapy, impaired health, and deterioration of quality of life, resulting in mandatory stoppage of the treatment. In the present study, the efficacy of an Ayurvedic formulation, Rasayana Avaleha, has been evaluated as an adjuvant medication to modern radiotherapy and chemotherapy. A total of 36 cancer patients were registered in this trial and were divided into two groups, group A and group B. In group A, the patients were treated with radiotherapy and chemotherapy along with adjuvant Rasayana Avaleha (RT + CT + RA), while in group B only radiotherapy and chemotherapy (RT + CT) were given, as the control group. After assessing the results, it was observed that Rasayana Avaleha gave better results in controlling the adverse effect of chemotherapy and radiotherapy in comparison with the control group. Therefore, Rasayana Avaleha has proved to be an effective adjuvant therapy in protecting patients from the adverse effects of chemotherapy and radiotherapy. PMID:22048532

  17. Apoptosis May Explain the Pharmacological Mode of Action and Adverse Effects of Isotretinoin, Including Teratogenicity.

    PubMed

    Melnik, Bodo C

    2017-02-08

    Isotretinoin (13-cis retinoic acid) is the most effective sebum-suppressive drug for the treatment of severe acne. Its effect depends on sebocyte apoptosis, which results from isotretinoin-induced expression of the apoptotic protein tumour necrosis factor-related apoptosis-inducing ligand, insulin-like growth factor-binding protein-3 and neutrophil gelatinase-associated lipocalin. This review proposes that the pharmacological mode of action of isotretinoin in the treatment of severe acne, acute promyelocytic leukaemia, and neuroblastoma results from apoptosis. Furthermore, apoptosis may be the underlying and unifying mechanism of the adverse effects of isotretinoin on neural crest cells (teratogenicity), hippocampal neurones (depression), epidermal keratinocytes and mucosa cells (mucocutaneous side-effects), hair follicle cells (telogen effluvium), intestinal epithelial cells (inflammatory bowel disease), skeletal muscle cells (myalgia and release of creatine kinase), and hepatocytes (release of transaminases and very low-density lipoproteins). Genetic variants of components of the apoptotic signalling cascade, such as RARA polymorphisms, might explain variations in the magnitude of isotretinoin-induced apoptotic signalling and apparently identify subgroups of patients who experience either stronger adverse effects with isotretinoin therapy or resistance to treatment.

  18. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus update.

    PubMed

    Mancini, G B John; Tashakkor, A Yashar; Baker, Steven; Bergeron, Jean; Fitchett, David; Frohlich, Jiri; Genest, Jacques; Gupta, Milan; Hegele, Robert A; Ng, Dominic S; Pearson, Glen J; Pope, Janet

    2013-12-01

    The Proceedings of a Canadian Working Group Consensus Conference, first published in 2011, provided a summary of statin-associated adverse effects and intolerance and management suggestions. In this update, new clinical studies identified since then that provide further insight into effects on muscle, cognition, cataracts, diabetes, kidney disease, and cancer are discussed. Of these, the arenas of greatest controversy pertain to purported effects on cognition and the emergence of diabetes during long-term therapy. Regarding cognition, the available evidence is not strongly supportive of a major adverse effect of statins. In contrast, the linkage between statin therapy and incident diabetes is more firm. However, this risk is more strongly associated with traditional risk factors for new-onset diabetes than with statin itself and any possible negative effect of new-onset diabetes during statin treatment is far outweighed by the cardiovascular risk reduction benefits. Additional studies are also discussed, which support the principle that systematic statin rechallenge, and lower or intermittent statin dosing strategies are the main methods for dealing with suspected statin intolerance at this time.

  19. Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

    PubMed

    Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

    2014-01-01

    The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications.

  20. Adverse reproductive effects of maternal low-dose melamine exposure during pregnancy in rats.

    PubMed

    Chu, Ching Yan; Tang, Ling Ying; Li, Lu; Shum, Alisa Sau Wun; Fung, Kwok Pui; Wang, Chi Chiu

    2017-01-01

    Melamine is a heterocyclic, aromatic amine and nitrogen-enriched environmental toxicant, found in not only adulterated foodstuffs but also industrial household tableware and paints. Previous studies demonstrated adverse effects of high-dose melamine on human infants and pregnant animals, but effects of low-dose melamine on pregnancy have not been reported. In this study, reproductive effects of low-dose melamine were investigated in pregnant rats. Melamine in the range of 12.5-50 mg/kg was administered to pregnant rats at different gestational stages. Maternal weight gain was not significantly affected, and other maternal morbidity was not observed. Low-dose melamine exposure during pregnancy increased fetal size but reduced somite number in gastrulation (GD8.5-GD10.5) and organogenesis (GD10.5-GD16.5) periods, and increased incidence of stillbirth in whole gestational period (GD0.5 to delivery). Embryotoxicity of melamine was further confirmed by whole embryo culture in vitro that melamine retarded embryonic growth, impaired development of brain and heart, and induced open neural tube and atrioventricular defects with increased apoptosis. In conclusion, adverse reproductive effects of low-dose melamine during pregnancy were identified in the developing rat embryos and the perinatal effects of melamine were gestational and developmental stage dependent. Detailed hazard and risk assessment of melamine in reproduction system are warrant. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 131-138, 2017.

  1. Time-Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach.

    PubMed

    Vogs, Carolina; Altenburger, Rolf

    2016-07-19

    Chemicals affect unicellular algae as a result of toxicokinetic and toxicodynamic processes. The internal concentration of chemicals in algae cells typically reaches equilibrium within minutes, while damage cumulatively increases over hours. The time gap between the steady state of internal exposure and damage development is thus suspected to span up to hours, mainly due to toxicodynamic processes. The quantification of rate-limited toxicodynamic processes, aggregated as a progressive effect from an initiating molecular event through biological key events toward the adverse outcome on algae growth inhibition, might discriminate between different adverse outcome pathways (AOPs). To support our hypothesis, we selected six chemicals according to different physicochemical properties and three distinctly dissimilar AOPs. The time courses of internal concentrations were linked to the observed affected Scenedesmus vacuolatus growth using toxicokinetic-toxicodynamic modeling. Effects on cell growth were explained by effect progression and not by the time to reach internal equilibrium concentration. Effect progression rates ranged over 6 orders of magnitude for all chemicals but varied by less than 1 order of magnitude within similar AOP (photosystem II inhibitors > reactive chemicals > lipid biosynthesis inhibitors), meaning that inhibitors of photosystem II advance an effect toward algae growth fastest compared to reactive chemicals and inhibitors of lipid biosynthesis.

  2. Novel Associations between FAAH Genetic Variants and Postoperative Central Opioid related Adverse Effects

    PubMed Central

    Sadhasivam, Senthilkumar; Zhang, Xue; Chidambaran, Vidya; Mavi, Jagroop; Pilipenko, Valentina; Mersha, Tesfaye B.; Meller, Jaroslaw; Kaufman, Kenneth M.; Martin, Lisa J.; McAuliffe, John

    2014-01-01

    Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year in due to opioid induced respiratory depression in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype blinded observational study 259 healthy children between 6 and 15 years that received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, respiratory depression (RD), postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (PACU) due to RD and PONV were analyzed. Five specific FAAH SNPs had significant associations with more than 2 fold increased risk for refractory PONV (adjusted p<0.0018), and nominal associations (p<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. FAAH SNP, rs324420 is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related respiratory depression, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy. PMID:25558980

  3. Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects.

    PubMed

    Sadhasivam, S; Zhang, X; Chidambaran, V; Mavi, J; Pilipenko, V; Mersha, T B; Meller, J; Kaufman, K M; Martin, L J; McAuliffe, J

    2015-10-01

    Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year because of opioid-induced respiratory depression (RD) in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype-blinded observational study in which 259 healthy children between 6 and 15 years of age who received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, RD, postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (postoperative anesthesia care unit, PACU) due to RD and PONV were analyzed. Five specific FAAH single nucleotide polymorphisms (SNPs) had significant associations with more than twofold increased risk for refractory PONV (adjusted P<0.0018), and nominal associations (P<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. The FAAH SNP, rs324420, is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related RD, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy.

  4. Adverse effects of drugs used in the management of constipation and diarrhoea.

    PubMed

    Gattuso, J M; Kamm, M A

    1994-01-01

    Most laxatives, if used intermittently in the absence of contraindications, are relatively safe. Bulking agents may diminish absorption of some minerals and drugs, but this is not usually clinically significant. Ispaghula can cause serious allergic reactions. The chronic ingestion of stimulant laxatives has been blamed for the development of the 'cathartic colon', but there are no definitive studies which have demonstrated this. Dantron (danthron) preparations should only be used in older patients and the terminally ill because of the risk of hepatotoxicity with this drug. Oral oxyphenisatine should no longer be used. Senna would appear to be the stimulant laxative of choice during pregnancy and lactation. Bisacodyl is the polyphenolic derivative of choice. Lactulose, sorbitol and lactilol rarely cause significant adverse effects. Magnesium salt laxatives and phosphate enemas can cause serious metabolic disturbances in babies and young children. Liquid paraffin is contraindicated if there is any risk of aspiration. Interference with the absorption of fat soluble vitamins would not appear to be clinically significant. Docusate sodium may potentiate the hepatotoxicity of other drugs, but reports of this are rare. The role of cisapride in constipation has not been established. Antidiarrhoeal drugs are second line drugs whose use is aimed at minimising inconvenience and discomfort. No antidiarrhoeals can be recommended for children under 4 years of age. Loperamide is the drug of choice in older children and adults. The atropine component of diphenoxylate/atropine combinations can cause significant adverse effects. Bismuth salicylate is an inconvenient treatment for travellers' diarrhoea as large frequent doses of the liquid formulation are needed. Some bismuth can be absorbed and there is the potential to cause encephalopathy. Octreotide, methysergide and cholestyramine have a role for specific causes of diarrhoea only. Octreotide is effective in high output states

  5. Vitamin D mitigates the adverse effects of obesity on breast cancer in mice.

    PubMed

    Swami, Srilatha; Krishnan, Aruna V; Williams, Jasmaine; Aggarwal, Abhishek; Albertelli, Megan A; Horst, Ronald L; Feldman, Brian J; Feldman, David

    2016-04-01

    Obesity is an established risk factor for postmenopausal breast cancer (BCa), insulin resistance, and vitamin D deficiency, and all contribute to increased synthesis of mammary estrogens, the drivers of estrogen receptor-positive (ER+) BCa growth. As both dietary vitamin D and calcitriol treatments inhibit breast estrogen synthesis and signaling, we hypothesized that vitamin D would be especially beneficial in mitigating the adverse effects of obesity on ER+BCa. To assess whether obesity exerted adverse effects on BCa growth and whether vitamin D compounds could reduce these unfavorable effects, we employed a diet-induced obesity (DIO) model in ovariectomized C57BL/6 mice. Breast tumor cells originally from syngeneic Mmtv-Wnt1 transgenic mice were then implanted into the mammary fat pads of lean and obese mice. DIO accelerated the initiation and progression of the mammary tumors. Treatments with either calcitriol or dietary vitamin D reduced the adverse effects of obesity causing a delay in tumor appearance and inhibiting continued tumor growth. Beneficial actions of treatments with vitamin D or calcitriol on BCa and surrounding adipose tissue included repressed Esr1, aromatase, and Cox2 expression; decreased tumor-derived estrogen and PGE2; reduced expression of leptin receptors; and increased adiponectin receptors. We demonstrate that vitamin D treatments decreased insulin resistance, reduced leptin, and increased adiponectin signaling and also regulated the LKB1/AMPK pathway contributing to an overall decrease in local estrogen synthesis in the obese mice. We conclude that calcitriol and dietary vitamin D, acting by multiple interrelated pathways, mitigate obesity-enhanced BCa growth in a postmenopausal setting.

  6. Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers.

    PubMed

    Weaver, Virginia M; Lee, Byung-Kook; Todd, Andrew C; Ahn, Kyu-Dong; Shi, Weiping; Jaar, Bernard G; Kelsey, Karl T; Lustberg, Mark E; Silbergeld, Ellen K; Parsons, Patrick J; Wen, Jiayu; Schwartz, Brian S

    2006-09-01

    Genetic polymorphisms that affect lead toxicokinetics or toxicodynamics may be important modifiers of risk for adverse outcomes in lead-exposed populations. We recently reported associations between higher patella lead, which is hypothesized to represent a lead pool that is both bioavailable and cumulative, and adverse renal outcomes in current and former Korean lead workers. In the present study, we assessed effect modification by polymorphisms in the genes encoding for delta-aminolevulinic acid dehydratase (ALAD), the vitamin D receptor (VDR), and endothelial nitric oxide synthase on those associations. Similar analyses were conducted with three other lead biomarkers. Renal function was assessed via blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, urinary N-acetyl-beta-D-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) microg/dl, 75.1 (101.1)and 33.6 (43.4) microg Pb/g bone mineral, and 0.63 (0.75) microg Pb/mg creatinine, respectively, in 647 lead workers. Little evidence of effect modification by genotype on associations between patella lead and renal outcomes was observed. The VDR polymorphism did modify associations between the other lead biomarkers and the serum creatinine and calculated creatinine clearance. Higher lead dose was associated with worse renal function in participants with the variant B allele. Models in two groups, dichotomized by median age, showed that this effect was present in the younger half of the population. Limited evidence of effect modification by ALAD genotype was observed; higher blood lead levels were associated with higher calculated creatinine clearance among participants with the ALAD(1-2) genotype. In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes.

  7. Effects of environmental cadmium and lead exposure on adults neighboring a discharge: Evidences of adverse health effects.

    PubMed

    Cabral, Mathilde; Toure, Aminata; Garçon, Guillaume; Diop, Cheikh; Bouhsina, Saâd; Dewaele, Dorothée; Cazier, Fabrice; Courcot, Dominique; Tall-Dia, Anta; Shirali, Pirouz; Diouf, Amadou; Fall, Mamadou; Verdin, Anthony

    2015-11-01

    The purpose of the study was to determine Pb and Cd concentrations in humans and to assess the effect of co-exposure to these metals on biomarkers of oxidative stress and nephrotoxicity. Blood and urine levels of Pb and Cd, oxidative stress and urinary renal biomarkers were measured in 77 subjects neighboring a discharge and 52 in the control site. Exposed subjects showed significantly higher levels of lead and cadmium in blood and urine than the controls. Excessive production of reactive oxygen species induced by these metals in exposed subjects conducted to a decrease in antioxidant defense system (GPx, Selenium, GSH) and an increase in lipid peroxidation (MDA). Moreover, changes in markers of nephrotoxicity (high urinary concentrations of total protein, RBP and CC16, as well as GSTα and LDH increased activities) suggested the occurrence of discrete and early signs of impaired renal function for the discharge neighboring population.

  8. Renal arteriography

    MedlinePlus

    Renal angiogram; Angiography - kidney; Renal angiography; Renal artery stenosis - arteriography ... an artery by a blood clot Renal artery stenosis Renal cell cancer Angiomyolipomas (noncancerous tumors of the ...

  9. Comparison of the Protective Effects of Erythropoietin and Melatonin on Renal Ischemia-Reperfusion Injury

    PubMed Central

    Banaei, Shokofeh; Ahmadiasl, Nasser; Alihemmati, Alireza

    2016-01-01

    Background Renal ischemia-reperfusion (IR) contributes to the development of acute renal failure (ARF). Oxygen free radicals are considered to be the principal components involved in the pathophysiological tissue alterations observed during renal IR. Objectives In this study, we compared the effects of melatonin (MEL) and erythropoietin (EPO), both known antioxidant and anti-inflammatory agents, on IR-induced renal injury in rats. Materials and Methods Wistar albino rats were unilaterally nephrectomized and then subjected to 45 minutes of renal pedicle occlusion followed by 24 hours of reperfusion. MEL (10 mg/kg, i.p) and EPO (5000 U/kg, i.p) were administered prior to the onset of ischemia. After 24 hours of reperfusion and following decapitation, blood samples were collected for the determination of the hemoglobin (Hb) and hematocrit (Hct) levels. Additionally, renal samples were taken for histological evaluation. Results Ischemia-reperfusion significantly decreased the observed Hb and Hct values. The histopathological findings in the IR group confirmed that there was an increase in the hyaline cast and thickening of the Bowman capsule basement membrane. Treatment with EPO or MEL significantly increased the Hb and Hct values. In the MEL + IR group, the histopathological changes were lower than those found in the EPO + IR group. Conclusions Treatment with EPO and MEL had a beneficial effect on renal IR injury. The results may also indicate that MEL protects against morphological damage better than EPO in renal IR injury. PMID:27921018

  10. Acute effects of ferumoxytol on regulation of renal hemodynamics and oxygenation

    PubMed Central

    Cantow, Kathleen; Pohlmann, Andreas; Flemming, Bert; Ferrara, Fabienne; Waiczies, Sonia; Grosenick, Dirk; Niendorf, Thoralf; Seeliger, Erdmann

    2016-01-01

    The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI). This study details the impact of ferumoxytol on regulation of renal hemodynamics and oxygenation. In 10 anesthetized rats, a single intravenous injection of isotonic saline (used as volume control) was followed by three consecutive injections of ferumoxytol to achieve cumulative doses of 6, 10, and 41 mg Fe/kg body mass. Arterial blood pressure, renal blood flow, renal cortical and medullary perfusion and oxygen tension were continuously measured. Regulation of renal hemodynamics and oxygenation was characterized by dedicated interventions: brief periods of suprarenal aortic occlusion, hypoxia, and hyperoxia. None of the three doses of ferumoxytol resulted in significant changes in any of the measured parameters as compared to saline. Ferumoxytol did not significantly alter regulation of renal hemodynamics and oxygenation as studied by aortic occlusion and hypoxia. The only significant effect of ferumoxytol at the highest dose was a blunting of the hyperoxia-induced increase in arterial pressure. Taken together, ferumoxytol has only marginal effects on the regulation of renal hemodynamics and oxygenation. This makes ferumoxytol a prime candidate as contrast agent for renal MRI including the assessment of renal blood volume fraction. PMID:27436132

  11. Protective effect of angiotensin II-induced increase in nitric oxide in the renal medullary circulation.

    PubMed

    Zou, A P; Wu, F; Cowley, A W

    1998-01-01

    This study examined the effect of intravenous infusion of subpressor doses of angiotensin (Ang II) on renal medullary blood flow (MBF), medullary partial oxygen pressure (PO2), and nitric oxide (NO) concentration under normal conditions and during reduction of the medullary nitric oxide synthase (NOS) activity in anesthetized rats. With laser Doppler flowmetry and polarographic measurement of PO2 with microelectrodes, Ang II (5 ng/kg per minute) did not alter renal cortical and medullary blood flows or medullary PO2. N(omega)-nitro-L-arginine methyl ester (L-NAME) was infused into the renal medullary interstitial space at a dose of 1.4 microg/kg per minute, a dose that did not significantly alter basal levels of MBF or PO2. Intravenous infusion of Ang II at the same dose in the presence of L-NAME decreased MBF by 23% and medullary PO2 by 28%, but it had no effect on cortical blood flow or arterial blood pressure. An in vivo microdialysis-oxyhemoglobin NO trapping technique was used in other rats to determine tissue NO concentrations using the same protocol. Ang II infusion increased tissue NO concentrations by 85% in the renal cortex and 150% in the renal medulla. Renal medullary interstitial infusion of L-NAME (1.4 microg/kg per minute) reduced medullary NO concentrations and substantially blocked Ang II-induced increases in NO concentrations in the renal medulla, but not in the renal cortex. Tissue slices of the renal cortex and medulla were studied to determine the effects of Ang II and L-NAME on the nitrite/nitrate production. Ang II stimulated the nitrite/nitrate production predominately in the renal medulla, which was significantly attenuated by L-NAME. We conclude that small elevations of circulating Ang II levels increase medullary NO production and concentrations, which plays an important role in buffering the vasoconstrictor effects of this peptide and in maintaining a constancy of MBF.

  12. Putative Kappa Opioid Heteromers As Targets for Developing Analgesics Free of Adverse Effects

    PubMed Central

    2015-01-01

    It is now generally recognized that upon activation by an agonist, β-arrestin associates with G protein-coupled receptors and acts as a scaffold in creating a diverse signaling network that could lead to adverse effects. As an approach to reducing side effects associated with κ opioid agonists, a series of β-naltrexamides 3–10 was synthesized in an effort to selectively target putative κ opioid heteromers without recruiting β-arrestin upon activation. The most potent derivative 3 (INTA) strongly activated KOR-DOR and KOR-MOR heteromers in HEK293 cells. In vivo studies revealed 3 to produce potent antinociception, which, when taken together with antagonism data, was consistent with the activation of both heteromers. 3 was devoid of tolerance, dependence, and showed no aversive effect in the conditioned place preference assay. As immunofluorescence studies indicated no recruitment of β-arrestin2 to membranes in coexpressed KOR-DOR cells, this study suggests that targeting of specific putative heteromers has the potential to identify leads for analgesics devoid of adverse effects. PMID:24978316

  13. Injected nanoparticles: the combination of experimental systems to assess cardiovascular adverse effects.

    PubMed

    Vlasova, Maria A; Tarasova, Olga S; Riikonen, Joakim; Raula, Janne; Lobach, Anatoly S; Borzykh, Anna A; Smirin, Boris V; Kauppinen, Esko I; Eletskii, Alexander V; Herzig, Karl-Heinz; Salonen, Jarno; Tavi, Pasi; Lehto, Vesa-Pekka; Järvinen, Kristiina

    2014-05-01

    When nanocarriers are used for drug delivery they can often achieve superior therapeutic outcomes over standard drug formulations. However, concerns about their adverse effects are growing due to the association between exposure to certain nanosized particles and cardiovascular events. Here we examine the impact of intravenously injected drug-free nanocarriers on the cardiovasculature at both the systemic and organ levels. We combine in vivo and in vitro methods to enable monitoring of hemodynamic parameters in conscious rats, assessments of the function of the vessels after sub-chronic systemic exposure to nanocarriers and evaluation of the direct effect of nanocarriers on vascular tone. We demonstrate that nanocarriers can decrease blood pressure and increase heart rate in vivo via various mechanisms. Depending on the type, nanocarriers induce the dilation of the resistance arteries and/or change the responses induced by vasoconstrictor or vasodilator drugs. No direct correlation between physicochemical properties and cardiovascular effects of nanoparticles was observed. The proposed combination of methods empowers the studies of cardiovascular adverse effects of the nanocarriers.

  14. Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms.

    PubMed

    Steiner, Sandro; Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

    2016-07-01

    Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially concerning the nature of the components of diesel exhaust responsible for the effects and how they could be eliminated from the exhaust. This review describes the fundamental properties of diesel exhaust as well as the human respiratory tract and concludes that adverse health effects of diesel exhaust not only emerge from its chemical composition, but also from the interplay between its physical properties, the physiological and cellular properties, and function of the human respiratory tract. Furthermore, the primary molecular and cellular mechanisms triggered by diesel exhaust exposure, as well as the fundamentals of the methods for toxicological testing of diesel exhaust toxicity, are described. The key aspects of adverse effects induced by diesel exhaust exposure described herein will be important for regulators to support or ban certain technologies or to legitimate incentives for the development of promising new technologies such as catalytic diesel particle filters.

  15. Putative kappa opioid heteromers as targets for developing analgesics free of adverse effects.

    PubMed

    Le Naour, Morgan; Lunzer, Mary M; Powers, Michael D; Kalyuzhny, Alexander E; Benneyworth, Michael A; Thomas, Mark J; Portoghese, Philip S

    2014-08-14

    It is now generally recognized that upon activation by an agonist, β-arrestin associates with G protein-coupled receptors and acts as a scaffold in creating a diverse signaling network that could lead to adverse effects. As an approach to reducing side effects associated with κ opioid agonists, a series of β-naltrexamides 3-10 was synthesized in an effort to selectively target putative κ opioid heteromers without recruiting β-arrestin upon activation. The most potent derivative 3 (INTA) strongly activated KOR-DOR and KOR-MOR heteromers in HEK293 cells. In vivo studies revealed 3 to produce potent antinociception, which, when taken together with antagonism data, was consistent with the activation of both heteromers. 3 was devoid of tolerance, dependence, and showed no aversive effect in the conditioned place preference assay. As immunofluorescence studies indicated no recruitment of β-arrestin2 to membranes in coexpressed KOR-DOR cells, this study suggests that targeting of specific putative heteromers has the potential to identify leads for analgesics devoid of adverse effects.

  16. Risk, mercury levels, and birds: relating adverse laboratory effects to field biomonitoring.

    PubMed

    Burger, J; Gochfeld, M

    1997-11-01

    There is an abundance of field data on levels of mercury in a variety of organisms and there are a number of studies that demonstrate the adverse effects of mercury on laboratory animals, but few studies examine the relationship between the two. Thus it is often difficult to determine the ecological relevance of mercury concentrations found in nature, or to predict the ecosystem consequences of current levels. In this paper we review the levels in tissues that are associated with adverse effects in birds from laboratory studies and compare these with levels found in wild bird populations in the New York Bight to provide a basis for interpreting values in avian populations. We use feathers from fledgling birds which would have been fed on locally obtained food to eliminate the problem of where toxic burdens were acquired by more mobile adult birds. Laboratory studies indicate that in some species mercury levels of 1.5 ppm in eggs and/or 5 to 40 ppm in the feathers of birds are associated with adverse effects, including impaired reproduction. We report egg levels in birds that range as high as 3.8 ppm and feather levels that range as high as 10.3 ppm, although means are much lower. The levels in eggs of some wild birds in the New York Bight are within the range known to lower hatchability, embryo and chick survival, and chick weight, all variables that reduce reproductive success. Species with high egg levels include Forster's tern (Sterna forsteri) and black skimmer (Rynchops niger). Levels in feathers of some young wild birds from the New York Bight are within the range associated with reduced hatchability of eggs, behavioral abnormalities of adults, and infertility. Species with dangerously elevated mercury levels in feathers include great egret (Ardea [=Egretta] alba), snowy egret [Egretta thula), and black skimmers.

  17. Epigenetics and transcriptomics to detect adverse drug effects in model systems of human development.

    PubMed

    Balmer, Nina V; Leist, Marcel

    2014-07-01

    Prenatal exposure to environmental chemicals or drugs has been associated with functional or structural deficits and the development of diseases in later life. For example, developmental neurotoxicity (DNT) is triggered by lead, and this compound may predispose to neurodegenerative diseases in later life. The molecular memory for such late consequences of early exposure is not known, but epigenetic mechanisms (modification of the chromatin structure) could take this role. Examples and underlying mechanisms have been compiled here for the field of DNT. Moreover, we addressed the question as to what readout is suitable for addressing drug memory effects. We summarize how complex developmental processes can be modelled in vitro by using the differentiation of human stem cells. Although cellular models can never replicate the final human DNT phenotype, they can model the adverse effect that a chemical has on key biological processes essential for organ formation and function. Highly information-rich transcriptomics data may inform on these changes and form the bridge from in vitro models to human prediction. We compiled data showing that transcriptome analysis can indicate toxicity patterns of drugs. A crucial question to be answered in our systems is when and how transcriptome changes indicate adversity (as opposed to transient adaptive responses), and how drug-induced changes are perpetuated over time even after washout of the drug. We present evidence for the hypothesis that changes in the histone methylation pattern could represent the persistence detector of an early insult that is transformed to an adverse effect at later time-points in life.

  18. Oral adverse effects of gastrointestinal drugs and considerations for dental management in patients with gastrointestinal disorders

    PubMed Central

    Karthik, Ramya; Karthik, K. S.; David, Chaya; Ameerunnisa; Keerthi, G.

    2012-01-01

    Gastrointestinal disease is associated with alterations in the mouth or influence the course of the dental diseases, and the dental health care workers are expected to recognize, diagnose, and treat oral conditions associated with gastrointestinal diseases and also provide safe and appropriate dental care for afflicted individuals. Drugs used in the management of these diseases result in oral adverse effects and also are known to interact with those prescribed during dental care. Hence, this article has reviewed the drug considerations and guidelines for drug use during dental management of patients with gastrointestinal diseases. PMID:23066260

  19. [Antivaccine misinformation about rate of adverse effects and toxicity of vaccines].

    PubMed

    Mats, A N; Gol'dshteĭn, A V

    2010-01-01

    Two widely known antivaccine inventions are discussed: "vaccination is accompanied by adverse effects, which exceeded complications of respective infections on frequency and severity" and "vaccines represent appalling conglomerate of toxic substances, which is unnaturally to administer to children". Informational and psychological nature of dissemination of these inventions is analyzed. On the basis of recent literature data conclusion was made about the absence of real toxicity (including neurotoxicity), carcinogenicity, allergenicity and autopathogenicity of phenol, folmaldehyde, aluminium hydroxide, Twin 80, squalen (MF59) and ethylmercury in concentrations found in vaccines of national immunization schedule.

  20. Antifibrotic effects of KS370G, a caffeamide derivative, in renal ischemia-reperfusion injured mice and renal tubular epithelial cells

    PubMed Central

    Chuang, Sung-Ting; Kuo, Yueh-Hsiung; Su, Ming-Jai

    2014-01-01

    Accumulating evidence suggests that renal tubulointerstitial fibrosis is a main cause of end-stage renal disease. Clinically, there are no beneficial treatments that can effectively reverse the progressive loss of renal functions. Caffeic acid phenethyl ester is a natural phenolic antifibrotic agent, but rapid decomposition by an esterase leads to its low bioavailability. In this study, we evaluated the effects of KS370G, a caffeic acid phenylethyl amide, on murine renal fibrosis induced by unilateral renal ischemia-reperfusion injury (IRI) and in TGF-β1 stimulated renal tubular epithelial cells (NRK52E and HK-2). In the animal model, renal fibrosis was evaluated at 14 days post-operation. Immediately following the operation, KS370G (10 mg/kg) was administered by oral gavage once a day. Our results show that KS370G markedly attenuates collagen deposition and inhibits an IRI-induced increase of fibronectin, vimentin, α-SMA and TGF-β1 expression and plasma TGF-β1 levels in the mouse kidney. Furthermore, KS370G reverses TGF-β1-induced downregulation of E-cadherin and upregulation of α-SMA and also decreases the expression of fibronectin, collagen I and PAI-1 and inhibits TGF-β1-induced phosphorylation of Smad2/3. These findings show the beneficial effects of KS370G on renal fibrosis in vivo and in vitro with the possible mechanism being the inhibition of the Smad2/3 signaling pathway. PMID:25056456

  1. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition.

    PubMed

    Vallon, Volker; Thomson, Scott C

    2017-02-01

    also uricosuric. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

  2. Are adverse effects of antiepileptic drugs different in symptomatic partial and idiopathic generalized epilepsies? The Portuguese-Brazilian validation of the Liverpool Adverse Events Profile.

    PubMed

    Martins, H H; Alonso, N B; Vidal-Dourado, M; Carbonel, T D; de Araújo Filho, G M; Caboclo, L O; Yacubian, E M; Guilhoto, L M

    2011-11-01

    We report the results of administration of the Portuguese-Brazilian translation of the Liverpool Adverse Events Profile (LAEP) to 100 patients (mean age=34.5, SD=12.12; 56 females), 61 with symptomatic partial epilepsy (SPE) and 39 with idiopathic generalized epilepsy (IGE) (ILAE, 1989) who were on a stable antiepileptic drug (AED) regimen and being treated in a Brazilian tertiary epilepsy center. Carbamazepine was the most commonly used AED (43.0%), followed by valproic acid (32.0%). Two or more AEDs were used by 69.0% of patients. The mean LAEP score (19 questions) was 37.6 (SD=13.35). The most common adverse effects were sleepiness (35.0%), memory problems (35.0%), and difficulty in concentrating (25.0%). Higher LAEP scores were associated with polytherapy with three or more AEDs (P=0.005), female gender (P<0.001), older age (P<0.001), and uncontrolled seizures (P=0.045). The intraclass coefficient (test-retest reliability) for LAEP overall score was 0.848 (95% CI=0.782-0.895), with a range from 0.370 (unsteadiness) to 0.750 (memory problems). Cronbach's α coefficient (internal consistency) was 0.903. The LAEP was highly correlated with Quality of Life in Epilepsy-31 inventory (r=-0.804, P>0.001) and Hospital Anxiety and Depression Scale (Depression: r=0.637, P<0.001; Anxiety: r=0.621, P<0.001) dimensions. LAEP overall scores were similar in people with SPE and IGE and were not helpful in differentiating adverse effects in these two groups. Clinical variables that influenced global LAEP were seizure frequency (P=0.050) and generalized tonic-clonic seizures in the last month (P=0.031) in the IGE group, and polytherapy with three or more AEDs (P=0.003 and P=0.003) in both IGE and SPE groups.

  3. How antibiotics can make us sick: the less obvious adverse effects of antimicrobial chemotherapy.

    PubMed

    Dancer, Stephanie J

    2004-10-01

    Antimicrobial agents are associated with side-effects, which are usually tolerated because the benefits of treatment outweigh the toxic effects. Clinicians know about these side-effects but are less likely to understand additional adverse events, such as the overgrowth of resistant microorganisms. Overgrowth can itself precipitate a secondary infection, which can be more difficult to treat. Resistant organisms then spread to other patients and the environment, and contribute to increasing antimicrobial resistance worldwide. Organisms exposed to antibiotics undergo molecular changes that might enhance virulence. Enhanced pathogenicity would affect patients, particularly if the organism is also multiply resistant. Clinicians have a responsibility to select the correct antibiotic as soon as they have diagnosed infection, but an absence of microbiological understanding and ignorance of the potential environmental effects have contributed to inappropriate prescribing. The less obvious results of antimicrobial consumption probably go unrecognised in routine clinical care.

  4. Atelocollagen-mediated Systemic Delivery Prevents Immunostimulatory Adverse Effects of siRNA in Mammals

    PubMed Central

    Inaba, Shinichiro; Nagahara, Shunji; Makita, Naoki; Tarumi, Yuzo; Ishimoto, Takuji; Matsuo, Seiichi; Kadomatsu, Kenji; Takei, Yoshifumi

    2012-01-01

    Short interfering RNA (siRNA) is a potent activator of the mammalian innate immune system. When considering possible clinical applications of siRNA for humans, the adverse immunostimulatory effects must also be taken into account. Here, we show that atelocollagen-mediated systemic delivery of siRNA without chemical modifications did not cause any immunostimulation in both animals and human peripheral blood mononuclear cells (PBMCs), even if the siRNA harbored an interferon (IFN)-inducible sequence. In contrast, systemic delivery of immunostimulatory RNA (isRNA)-mediated by a cationic lipid (such as Invivofectamine) induced potent type-I IFNs and inflammatory cytokines. Regarding the mechanism by which the isRNA/atelocollagen complex avoided adverse effects on immunostimulation, we revealed that this complex was not incorporated into PBMCs. On the other hand, Invivofectamine delivered isRNA into PBMCs. The use of either atelocollagen or Invivofectamine as a vehicle elicited significant and undistinguishable therapeutic effects in a contact hypersensitivity (CHS) inflammatory model mouse, when we intravenously injected the siRNA targeting monocyte chemoattractant protein-1 as the complex. For the goal of realizing siRNA-based medicines for humans, atelocollagen is an excellent and promising delivery vehicle, and it has the useful advantage of evading detection by the “radar” of innate immunity. PMID:22031237

  5. Uncertainty quantification of adverse human health effects from continuously released contaminant sources in groundwater systems

    NASA Astrophysics Data System (ADS)

    Zarlenga, Antonio; de Barros, Felipe P. J.; Fiori, Aldo

    2016-10-01

    We propose a computationally efficient probabilistic modeling methodology to estimate the adverse effects on humans of exposure to contaminated groundwater. Our work is aligned with the standard suggested by the regulatory agencies and allows to propagate uncertainty from hydrogeological, toxicological and behavioral parameters to the final health risk endpoint. The problem under consideration consists of a contaminated aquifer supplying water to a population. Contamination stems from a continuous source that feeds a steady plume which constitutes the hazard source. This scenario is particularly suited for NAPL pollutants. The erratic displacement of the contaminant plume in groundwater, due to the spatial variability of hydraulic conductivity, is characterized within the Lagrangian stochastic framework which enables the complete probabilistic characterization of the contaminant concentration at an environmentally sensitive location. Following the probabilistic characterization of flow and transport, we quantify the adverse health effects on humans. The dose response assessment involves the estimation of the uncertain effects of the exposure to a given contaminant while accounting for the exposed individual's metabolism. The model integrates groundwater transport, exposure and human metabolism in a comprehensive probabilistic framework which allows the assessment of the risk probability through a novel simple analytical solution. Aside from its computational efficiency, the analytical features of the framework allows the assessment of uncertainty arising from the hydrogeological parameters.

  6. Cyproheptadine for prevention of neuropsychiatric adverse effects of efavirenz: a randomized clinical trial.

    PubMed

    Dabaghzadeh, Fatemeh; Ghaeli, Padideh; Khalili, Hossein; Alimadadi, Abbas; Jafari, Sirous; Akhondzadeh, Shahin; Khazaeipour, Zahra

    2013-03-01

    Cyproheptadine prevention of the neuropsychiatric adverse effects of an antiretroviral regimen including efavirenz has been evaluated in a randomized clinical trial. Twenty-five patients (16 males and 9 females with mean±SD ages of 36±9 years) in a cyproheptadine group, and 26 patients (17 males and 9 females with mean±SD ages of 34±7 years) in a control group completed the trial. Sexual contact and injection drug use were the main routs of HIV infection in both groups. The patients' neuropsychiatric adverse effects were evaluated based on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation, and Somatization Subscale of Symptom Checklist 90 at baseline and 4 weeks after treatment. Cyproheptadine significantly decreased the scores of Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation of the patients after 4 weeks in comparison with control group. All of the scores increased in control group following antiretroviral therapy. Although short duration of the patients' follow-up was a major limitation of the study, the results of the study showed that cyprohepradine is effective in prevention of depression, anxiety, hallucination, aggressive behaviors, emotional withdrawal, poor rapport, poor impulse control, active social avoidance, suicidal ideation, and improved sleep quality of HIV-positive patients after initiation of antiretroviral therapy including efavirenz.

  7. Effect of blood transfusions on canine renal allograft survival

    SciTech Connect

    van der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-04-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Furthermore, no improvement in graft survival has been found after a peroperative transfusion of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion or irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

  8. Effect of blood transfusions on canine renal allograft survival

    SciTech Connect

    Van Der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-04-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Futhermore, no improvement in graft survival has been found after a peroperative transfuson of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion of irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

  9. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation

    PubMed Central

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen

    2016-01-01

    Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  10. Adverse and beneficial effects of plant extracts on skin and skin disorders.

    PubMed

    Mantle, D; Gok, M A; Lennard, T W

    2001-06-01

    Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively. Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for primary health care. Approximately one-third of all traditional medicines are for treatment of wounds or skin disorders, compared to only 1-3% of modern drugs. The use of such medicinal plant extracts for the treatment of skin disorders arguably has been based largely on historical/anecdotal evidence, since there has been relatively little data available in the scientific literature, particularly with regard to the efficacy of plant extracts in controlled clinical trials. In this article therefore, adverse and beneficial aspects of medicinal plants relating to skin and skin disorders have been reviewed, based on recently available information from the peer-reviewed scientific literature. Beneficial aspects of medicinal plants on skin include: healing of wounds and burn injuries (especially Aloe vera); antifungal, antiviral, antibacterial and acaricidal activity against skin infections such as acne, herpes and scabies (especially tea tree (Melaleuca alternifolia) oil); activity against inflammatory/immune disorders affecting skin (e.g. psoriasis); and anti-tumour promoting activity against skin cancer (identified using chemically-induced two-stage carcinogenesis in mice). Adverse effects of plants on skin reviewed include: irritant contact dermatitis caused mechanically (spines, irritant hairs) or by irritant chemicals in plant sap (especially members of the Ranunculaceae, Euphorbiaceae and Compositae plant families); phytophotodermatitis resulting from skin contamination by plants containing furocoumarins, and subsequent exposure to UV light (notably members of the Umbelliferae and Rutaceae plant families); and immediate (type I) or delayed hypersensitivity contact reactions mediated by the immune system in individuals sensitized to plants

  11. Effect of Organophosphate Compounds on Renal Function and Transport.

    DTIC Science & Technology

    1983-09-15

    cholinomimetic- induced diuresis , they do demonstrate a direct action of these compounds on renal cell electrolyte balance. Carter’s group did not examine the...Carrier. J. Friborg and 3. P. Onay, Vasodilators, intrarenal blood flow, and natriuresis in the dog. Amer. 3. Physiol., 221 (1971) 92- 98. 11. U.K...tylchol insestaraso activity. Diochem. Pharmacol., 7 (1961) 88-94. 19. 3.P. Hayslett, U. Kashgarian and F.H. Epstein, The diuresis of renal 17

  12. Ameliorative Effect of Recombinant Human Erythropoietin and Ischemic Preconditioning on Renal Ischemia Reperfusion Injury in Rats

    PubMed Central

    Elshiekh, Mohammed; Kadkhodaee, Mehri; Seifi, Behjat; Ranjbaran, Mina; Ahghari, Parisa

    2015-01-01

    Background: Ischemia-reperfusion (IR) injury is one of the most common causes of renal dysfunction. There is increasing evidence about the role of the reactive oxygen species (ROS) in these injuries and endogenous antioxidants seem to have an important role in decreasing the renal tissue injury. Objectives: The aim of this study was to compare the effect of recombinant human erythropoietin (EPO) and ischemic preconditioning (IPC) on renal IR injury. Materials and Methods: Twenty four male Wistar rats were allocated into four experimental groups: sham-operated, IR, EPO + IR, and IPC + IR. Rats were underwent 50 minutes bilateral ischemia followed by 24 hours reperfusion. Erythropoietin (5000 IU/kg, i.p) was administered 30 minutes before onset of ischemia. Ischemic preconditioning was performed by three cycles of 3 minutes ischemia followed by 3 minutes reperfusion. Plasma concentrations of urea and creatinine were measured. Kidney samples were taken for reactive oxidative species (ROS) measurement including superoxide dismutase (SOD) activity, glutathione (GSH) contents, and malondialdehyde (MDA) levels. Results: Compared to the sham group, IR led to renal dysfunction as evidenced by significantly higher plasma urea and creatinine. Treatment with EPO or IPC decreased urea, creatinine, and renal MDA levels and increased SOD activity and GSH contents in the kidney. Conclusions: Pretreatment with EPO and application of IPC significantly ameliorated the renal injury induced by bilateral renal IR. However, both treatments attenuated renal dysfunction and oxidative stress in kidney tissues. There were no significant differences between pretreatment with EPO or application of IPC. PMID:26866008

  13. Effect of carotid occlusion and of perfusion pressure on renal function in conscious dogs.

    PubMed

    Gross, R; Kirchheim, H; Ruffmann, K

    1981-06-01

    We studied the effect of bilateral common carotid occlusion (implanted pneumatic cuffs) on renal blood flow (electromagnetic flowmeter) and renal function (implanted ureteral catheter) in nine chronically instrumented, conscious dogs on a high sodium diet (14 mmol/kg body weight per day). By means of suprarenal aortic constriction (pneumatic cuff) the influence of renal perfusion pressure was investigated. There was no change in renal blood flow or glomerular filtration rate (inulin clearance) with either reflexly increasing (+49.6%) or constant renal perfusion pressure. Carotid occlusion caused an increase of urine output by 80.5% and of sodium excretion by 85.3% due to a fall in fractional sodium reabsorption (-0.9%) when renal perfusion pressure was allowed to rise. Neither an increase of diuresis or sodium excretion nor an antinatriuresis was observed when renal perfusion pressure was kept constant during carotid occlusion. We conclude that, in conscious dogs at rest, the moderate sympathetic activation associated with carotid occlusion is too small to induce renal sympathetic vasoconstriction or antinatriuresis. The "carotid sinus polyuria" is a pressure-diuresis.

  14. Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis

    PubMed Central

    Ryti, Niilo R.I.; Guo, Yuming; Jaakkola, Jouni J.K.

    2015-01-01

    Background There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. Objective We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Data sources and extraction Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. “Cold spell” was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Data synthesis Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0–64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Conclusions Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Citation Ryti NR, Guo Y, Jaakkola JJ. 2016. Global

  15. Renal and blood pressure effects from environmental cadmium exposure in Thai children.

    PubMed

    Swaddiwudhipong, Witaya; Mahasakpan, Pranee; Jeekeeree, Wanpen; Funkhiew, Thippawan; Sanjum, Rungaroon; Apiwatpaiboon, Thitikarn; Phopueng, Ittipol

    2015-01-01

    Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of β2-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥ 1 μg/g creatinine. The prevalence of urinary cadmium ≥ 1 μg/g creatinine was significantly higher in girls and in those consuming rice grown in cadmium-contaminated areas. The geometric mean levels of urinary β2-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary β2-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children.

  16. Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation

    PubMed Central

    Mills, Nicholas L.; Miller, Mark R.; Lucking, Andrew J.; Beveridge, Jon; Flint, Laura; Boere, A. John F.; Fokkens, Paul H.; Boon, Nicholas A.; Sandstrom, Thomas; Blomberg, Anders; Duffin, Rodger; Donaldson, Ken; Hadoke, Patrick W.F.; Cassee, Flemming R.; Newby, David E.

    2011-01-01

    Aim Exposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution. Methods and results To determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 ± 4 vs. 133 ± 3 mmHg, P< 0.05) and attenuated vasodilatation to bradykinin (P= 0.005), acetylcholine (P= 0.008), and sodium nitroprusside (P< 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n= 6–9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P< 0.001) and sodium-nitroprusside (P= 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate. Conclusion Combustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions. PMID:21753226

  17. Effects of a new dihydropyridine derivative, S12968 (pranedipine), and its stereoisomer, S12967, on renal effects of endothelin-1.

    PubMed

    Montañés, I; Flores, O; Eleno, N; López-Novoa, J M

    1994-11-01

    The purpose of the present study was to assess in rats the prevention by two enantiomers of a new dihydropyridine derivative (pranedipine) (called S12967 for the dextrogyre (+) and S12968 for the levogyre (-) molecules) of the renal and cardiovascular effects induced by endothelin-1. The injection of endothelin-1 (1 nmol/kg body weight) induced a sharp and transient decrease in urine flow, sodium and potassium excretion, glomerular filtration rate, renal plasma flow, and renal blood flow, a significant increase in renal vascular resistance, and a small but significant increase in arterial pressure. Treatment with S12968 alone (0.3 mg/kg) induced a 2.5-fold increase in urine flow and potassium excretion and a 4.5-fold increase in sodium excretion. Pretreatment with S12968 completely blocked the endothelin-1 induced increase in arterial pressure, did not affect the acute effect of endothelin-1 on urine flow, sodium and potassium excretion, filtration rate, and renal blood flow, but blunted the effect on renal vascular resistance. Administration of S12967 alone (1 mg/kg) did not induce changes in either renal function or arterial pressure. In S12967-treated animals, endothelin-1 also induced a transient increase in arterial pressure nad renal vascular resistance but failed to change renal function in a significant manner. In summary, the above reported experiments show that at the higher, nonhypotensive doses, the levogyre enantiomer (S12968) of a new dihydropyridine derivative (pranedipine) completely prevented the hypertensive effect of endothelin 1, and partially prevented the effect of endothelin-1 on renal vascular resistance. The dextrogyre enantiomer (S12967) had almost no effect on either mean arterial pressure or renal vascular resistance but completely blocked the endothelin-1-induced decrease in urine flow and urinary sodium excretion.

  18. A re-appraisal of volume status and renal function impairment in chronic heart failure: combined effects of pre-renal failure and venous congestion on renal function.

    PubMed

    Sinkeler, Steef J; Damman, Kevin; van Veldhuisen, Dirk J; Hillege, Hans; Navis, Gerjan

    2012-03-01

    The association between cardiac failure and renal function impairment has gained wide recognition over the last decade. Both structural damage in the form of systemic atherosclerosis and (patho) physiological hemodynamic changes may explain this association. As regards hemodynamic factors, renal impairment in chronic heart failure is traditionally assumed to be mainly due to a decrease in cardiac output and a subsequent decrease in renal perfusion. This will lead to a decrease in glomerular filtration rate and a compensatory increase in tubular sodium retention. The latter is a physiological renal response aimed at retaining fluids in order to increase cardiac filling pressure and thus renal perfusion. In heart failure, however, larger increases in cardiac filling pressure are needed to restore renal perfusion and thus more volume retention. In this concept, in chronic heart failure, an equilibrium exists where a certain degree of congestion is the price to be paid to maintain adequate renal perfusion and function. Recently, this hypothesis was challenged by new studies, wherein it was found that the association between right-sided cardiac filling pressures and renal function is bimodal, with worse renal function at the highest filling pressures, reflecting a severely congested state. Renal hemodynamic studies suggest that congestion negatively affects renal function in particular in patients in whom renal perfusion is also compromised. Thus, an interplay between cardiac forward failure and backward failure is involved in the renal function impairment in the congestive state, presumably along with other factors. Only few data are available on the impact of intervention in volume status on the cardio-renal interaction. Sparse data in cardiac patients as well as evidence from cohorts with primary renal disease suggest that specific targeting of volume overload may be beneficial for long-term outcome, in spite of a certain further decrease in renal function, at least

  19. Organophosphate pesticides exposure among farmworkers: pathways and risk of adverse health effects.

    PubMed

    Suratman, Suratman; Edwards, John William; Babina, Kateryna

    2015-01-01

    Organophosphate (OP) compounds are the most widely used pesticides with more than 100 OP compounds in use around the world. The high-intensity use of OP pesticides contributes to morbidity and mortality in farmworkers and their families through acute or chronic pesticides-related illnesses. Many factors contributing to adverse health effects have been investigated by researchers to determine pathways of OP-pesticide exposure among farmers in developed and developing countries. Factors like wind/agricultural pesticide drift, mixing and spraying pesticides, use of personal protective equipment (PPE), knowledge, perceptions, washing hands, taking a shower, wearing contaminated clothes, eating, drinking, smoking, and hot weather are common in both groups of countries. Factors including low socioeconomic status areas, workplace conditions, duration of exposure, pesticide safety training, frequency of applying pesticides, spraying against the wind, and reuse of pesticide containers for storage are specific contributors in developing countries, whereas housing conditions, social contextual factors, and mechanical equipment were specific pathways in developed countries. This paper compares existing research in environmental and behavioural exposure modifying factors and biological monitoring between developing and developed countries. The main objective of this review is to explore the current depth of understanding of exposure pathways and factors increasing the risk of exposure potentially leading to adverse health effects specific to each group of countries.

  20. Noise monitoring and adverse health effects in residents in different functional areas of Luzhou, China.

    PubMed

    Han, Zhi-Xia; Lei, Zhang-Heng; Zhang, Chun-Lian; Xiong, Wei; Gan, Zhong-Lin; Hu, Ping; Zhang, Qing-Bi

    2015-03-01

    The purpose of the study was to investigate the noise pollution situation and the resulting adverse effect on residents' health in Luzhou, China, to provide data for noise pollution prevention policies and interventions. Four different functional areas (commercial, construction, residential, and transportation hub areas) were chosen to monitor noise level for 3 months. The survey was performed by questionnaire on the spot on randomly selected individuals; it collected data on the impact of noise on residents' health (quality of sleep, high blood pressure, subjective feeling of nervous system damage, and attention) as well as the knowledge of noise-induced health damage, the degree of adaptation to noise, and their solutions. The noise levels of residential, commercial, transportation, and construction areas exceeded the national standards (P < .001). Sleep quality, prevalence of hypertension, and attention in transportation hub areas were significantly different from those in the other 3 areas (P < .05); only 24.46% of people knew the health hazards associated with noise; 64.57% of residents have adapted to the current noise environment. Most of them have to close the doors and windows to reduce noise. The noise pollution situation in Luzhou, China, is serious, especially the traffic noise pollution. Residents pay less attention to it and adopt single measures to reduce the noise. We should work toward the prevention and control of traffic noise and improve the residents' awareness to reduce the adverse health effects of noise.

  1. Wood combustion particles induce adverse effects to normal and diseased airway epithelia.

    PubMed

    Krapf, Manuel; Künzi, Lisa; Allenbach, Sandrine; Bruns, Emily A; Gavarini, Ilaria; El-Haddad, Imad; Slowik, Jay G; Prévôt, André S H; Drinovec, Luka; Močnik, Griša; Dümbgen, Lutz; Salathe, Matthias; Baumlin, Nathalie; Sioutas, Constantinos; Baltensperger, Urs; Dommen, Josef; Geiser, Marianne

    2017-02-27

    Residential wood burning is a major source of poorly characterized, deleterious particulate matter, whose composition and toxicity may vary with wood type, burning condition and photochemical age. The causative link between ambient wood particle constituents and observed adverse health effects is currently lacking. Here we investigate the relationship between chemical properties of primary and atmospherically aged wood combustion particles and acute toxicity in human airway epithelial cells. Emissions from a log wood burner were diluted and injected into a smog chamber for photochemical aging. After concentration-enrichment and removal of oxidizing gases, directly emitted and atmospherically aged particles were deposited on cell cultures at the air-liquid interface for 2 hours in an aerosol deposition chamber mimicking physiological conditions in lungs. Cell models were fully differentiated normal and diseased (cystic fibrosis and asthma) human bronchial epithelia (HBE) and the bronchial epithelial cell line BEAS-2B. Cell responses were assessed at 24 hours after aerosol exposure. Atmospherically relevant doses of wood combustion particles significantly increased cell death in all but the asthma cell model. Expression of oxidative stress markers increased in HBE from all donors. Increased cell death and inflammatory responses could not be assigned to a single chemical fraction of the particles. Exposure to primary and aged wood combustion particles caused adverse effects to airway epithelia, apparently induced by several interacting components.

  2. Comparison of gastrointestinal adverse effects of ketoprofen between adult and young cats.

    PubMed

    Takata, Kenji; Hikasa, Yoshiaki; Satoh, Hiroshi

    2012-12-01

    This study elucidated differences in predisposition to the gastrointestinal adverse effects of ketoprofen between young and adult cats. Ketoprofen was administered subcutaneously (2.0 mg/kg, s.c.) once a day for 3 days. The animals were sacrificed 24 hr after final injection to allow examination of gastrointestinal mucosal lesions. Ketoprofen caused gastric lesions in adult cats (>6 months) but not in young cats (<3 months). Ketoprofen caused more severe small intestinal lesions in adult cats than in young cats. In the study of prevention of lipopolysaccharide (LPS)-induced hyperthermia using ketoprofen, young and adult cats of both sexes were administered LPS (0.3 μg/kg, intravenously), and body temperature was measured 24 hr later. Ketoprofen was administered subcutaneously 30 min before LPS injection. LPS-induced hyperthermia was almost completely inhibited by pretreatment with ketoprofen in both adult and young cats. In the pharmacokinetics of ketoprofen, plasma concentrations were analyzed by high-performance liquid chromatography. No significant differences were observed in plasma concentrations of two mirror-image R(-) and S(+) ketoprofen between young and adult cats from 0.5-4 hr after injection. As observed in a previous study using flunixin, the degree of gastrointestinal damage was unrelated to plasma concentrations of ketoprofen. The results of this study demonstrated that ketoprofen is safer for use in young cats than in adult cats from the viewpoint of gastrointestinal adverse effects.

  3. HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

    PubMed

    Nicol, Alcina F; de Andrade, Cecilia V; Russomano, Fabio B; Rodrigues, Luana S L; Oliveira, Nathalia S; Provance, David William; Nuovo, Gerard J

    2015-12-01

    The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings.

  4. [Antibodies, human leukocyte antigens, and biomodulators in transfusion-related acute adverse effects].

    PubMed

    Martínez Álvarez, Julio César

    2013-01-01

    With the onset of the AIDS epidemic, major changes occurred in blood banking and transfusion medicine. These changes occurred mainly in donor selection and screening tests for infectious diseases, blood centers modified their organizational philosophy regarding quality. Transfusion of blood products are procedures that allow us to correct the haematology deficiencies for which was indicated. But today, despite the strict controls that precede transfusion,recipients may have undesirable effects, which are known as adverse effects or adverse reactions to transfusion. Antibodies and antigens of the HLA system plays a role in a series of events related to transfusion, such as immunological platelet refractoriness, febrile non-haemolytic transfusion reactions, transfusion related acute lung injury (TRALI) and transfusion-associated graft-versus-host disease. The determination of anti-HLA antibodies is evidence that in most developed countries is used on a daily basis in the regular assessment of patients multitransfused or waiting lists for organs from deceased donors. The biomodulators are able to modify biological responses which act in sequence to lead to the differentiation of T lymphocytes. These agents may subcategorizes those which facilitate a normal immune response, those stimulates the immune response, those are capable of inducing immunosuppression not cytotoxic, and those enhancing the ability of the host to tolerate damage by cytotoxic treatment (transfusion or transplant).

  5. Investigating clandestine drug laboratories: adverse medical effects in law enforcement personnel.

    PubMed

    Burgess, J L; Barnhart, S; Checkoway, H

    1996-10-01

    A retrospective cohort study was conducted among an international group of 46 law enforcement chemists and 13 Washington State clandestine drug laboratory investigation team members with more than 2,800 combined investigations. Each participant completed a questionnaire concerning previous drug laboratory investigations and adverse health effects during response activities. Methamphetamine laboratories accounted for 81-97% of all responses. Total illness incident rates varied between 0.75-3.4% of responses. Most exposures were through inhalation, and many occurred in the years prior to use of personal protective equipment. Symptoms were primarily those of headache and respiratory, mucous membrane, and skin irritation. Most illness episodes occurred during the processing phase of laboratory responses, and none occurred during the entry phase. A majority of illness episodes occurred in laboratories with leak/spills, fire/explosion, or uncontrolled reactions. Responding to an active laboratory was associated with a 7 to 15-fold risk of becoming ill as compared with setup, in-transit, or former (equipment removed) laboratory responses. No other laboratories characteristics were consistently associated with a significantly elevated relative risk of adverse health effects.

  6. Gratitude buffers the adverse effect of viewing the thin ideal on body dissatisfaction.

    PubMed

    Homan, Kristin J; Sedlak, Brittany L; Boyd, Elizabeth A

    2014-06-01

    Gratitude has robust associations with multiple aspects of well-being. However, little research has explored whether the psychological benefits of gratitude extend to body image. We used a repeated measures experimental design to test whether a brief period of grateful reflection would buffer the adverse effect of exposure to thin-ideal media. Female undergraduates (N=67) completed three sessions one week apart. The conditions were specifically designed to isolate (a) the effects of viewing thin models on body dissatisfaction and (b) the moderating effect of grateful contemplation. Results showed that body dissatisfaction scores were lower for women who engaged in a brief period of grateful contemplation before viewing photographs of thin models than for women who reflected upon life hassles before viewing the same photographs. The magnitude of this decrease depended on BMI. Gratitude offers an innovative direction for future research directed toward helping women to accept their bodies.

  7. Adverse effects of fullerenes (nC60) spiked to sediments on Lumbriculus variegatus (Oligochaeta).

    PubMed

    Pakarinen, K; Petersen, E J; Leppänen, M T; Akkanen, J; Kukkonen, J V K

    2011-12-01

    Effects of fullerene-spiked sediment on a benthic organism, Lumbriculus variegatus (Oligochaeta), were investigated. Survival, growth, reproduction, and feeding rates were measured to assess possible adverse effects of fullerene agglomerates produced by water stirring and then spiked to a natural sediment. L. variegatus were exposed to 10 and 50 mg fullerenes/kg sediment dry mass for 28 d. These concentrations did not impact worm survival or reproduction compared to the control. Feeding activities were slightly decreased for both concentrations indicating fullerenes' disruptive effect on feeding. Depuration efficiency decreased in the high concentration only. Electron and light microscopy and extraction of the worm fecal pellets revealed fullerene agglomerates in the gut tract but not absorption into gut epithelial cells. Micrographs also indicated that 16% of the epidermal cuticle fibers of the worms were not present in the 50 mg/kg exposures, which may make worms susceptible to other contaminants.

  8. Effects of Renal Denervation Documented in the Austrian National Multicentre Renal Denervation Registry

    PubMed Central

    Lambert, Thomas; Steinwender, Clemens; Weber, Thomas; Suppan, Markus; Brussee, Helmut; Koppelstätter, Christian; Kerschbaum, Julia; Watschinger, Bruno; Hohenstein-Scheibenecker, Katharina; Reindl-Schwaighofer, Roman; Sturmberger, Thomas; Kindslehner, Claudia; Weiss, Thomas Werner; Rohla, Miklos; Gruener, Peter; Maister, Petra; Auer, Johann; Dechant, Cornelia; Sykora, Josef; Krismer, Christoph; Glaser, Stefan; Zweiker, Robert

    2016-01-01

    Renal denervation (RDN) is a new procedure for treatment-resistant hypertensive patients. In order to monitor all procedures undergone in Austria, the Austrian Society of Hypertension established the investigator-initiated Austrian Transcatheter Renal Denervation (TREND) Registry. From April 2011 to September 2014, 407 procedures in 14 Austrian centres were recorded. At baseline, office and mean 24-h ambulatory blood pressure (ABP) were 171/94 and 151/89 mmHg, respectively, and patients were taking a median of 4 antihypertensive medications. Mean 24-h ABP changes after 2–6 weeks, 3, 6 and 12 months were -11/-6, -8/-4, -8/-5 and -10/-6 mmHg (p<0.05 at all measurements), respectively. The periprocedural complication rate was 2.5%. Incidence of long-term complications during follow-up (median 1 year) was 0.5%. Office BP and ABP responses showed only a weak correlation (Pearson coefficient 0.303). Based on the data from the TREND registry, ambulatory blood pressure monitoring in addition to office BP should be used for patient selection as well as for monitoring response to RDN. Furthermore, criteria for optimal patient selection are suggested. PMID:27529426

  9. Renal Side Effects of Non-Steroidal Anti-Inflammatory Drugs in Neonates

    PubMed Central

    Allegaert, Karel; de Hoon, Jan; Debeer, Anne; Gewillig, Marc

    2014-01-01

    Non-steroidal anti-inflammatory drugs like ibuprofen or indomethacin are commonly prescribed drugs to induce pharmacologic closure of a patent ductus arteriosus in preterm neonates. Based on a recently published Cochrane meta-analysis, both drugs are equally effective to induce closure. Drug choice can therefore be based on differences in side effects or pharmaco-economic arguments. The current review quantifies the negative impact of either ibuprofen or indomethacin on renal function, including diuresis, glomerular filtration rate and renal tubular function. Both ibuprofen and indomethacin have a quantifiable impact on renal function. However, compared to ibuprofen, the negative impact of indomethacin is more pronounced. PMID:27713258

  10. Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

    PubMed Central

    2013-01-01

    Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised

  11. Effectiveness of Topical Chia Seed Oil on Pruritus of End-stage Renal Disease (ESRD) Patients and Healthy Volunteers

    PubMed Central

    Jeong, Se Kyoo; Park, Hyun Jung; Park, Byeong Deog

    2010-01-01

    Background Several studies have been performed to evaluate the efficacy of dietary n-3 fatty acid for patients with renal dysfunction. While about 40% to 80% of patients with end-stage renal disease (ESRD) complain about pruritus and xerosis, there are few reports on the effects of topical n-3 fatty acid on these symptoms. Objective In order to investigate the possible beneficial effects of topical n-3 fatty acid, oils extracted from chia (Salvia hispanica) seed were formulated into topical products, the effects of which were measured. Methods Five healthy volunteers having xerotic pruritus symptoms and 5 patients with pruritus caused by either ESRD or diabetes were involved in this study. A topical formulation containing 4% chia seed oils were applied for an 8-week duration. Subjective itching symptoms were assessed on a 6-point scale, as were other skin functions, namely transepidermal water loss and skin capacitance. Results After the 8 weeks of application, significant improvements in skin hydration, lichen simplex chronicus, and prurigo nodularis were observed in all patients. A similar improvement was also observed among healthy volunteers with xerotic pruritus. Improvement of epidermal permeability barrier function and skin hydration, represented by trans-epidermal water loss and skin capacitance, respectively, were also observed. No adverse effects were observed in all the tested patients and volunteers. Conclusion Chia seed oil can be used as an adjuvant moisturizing agent for pruritic skin, including that of ESRD patients. PMID:20548903

  12. Economic Adversity and Children’s Sleep Problems: Multiple Indicators and Moderation of Effects

    PubMed Central

    El-Sheikh, Mona; Bagley, Erika J.; Keiley, Margaret; Elmore-Staton, Lori; Chen, Edith; Buckhalt, Joseph A.

    2014-01-01

    Objective Toward explicating relations between economic adversity and children’s sleep, we examined associations between multiple indicators of socioeconomic status (SES)/adversity and children’s objectively and subjectively derived sleep parameters; ethnicity was examined as potential moderator. Methods Participants were 276 third- and fourth-grade children and their families (133 girls; M age = 9.44 years; SD = .71): 66% European American (EA) and 34% African American (AA). Four SES indicators were used: income-to-needs ratio, perceived economic well-being, maternal education, and community poverty. Children wore actigraphs for 7 nights and completed a self-report measure to assess sleep problems. Results Objectively and subjectively assessed sleep parameters were related to different SES indicators, and overall worse sleep was evident for children from lower SES homes. Specifically, children from homes with lower income-to-needs ratios had higher levels of reported sleep/wake problems. Parental perceived economic well-being was associated with shorter sleep minutes and greater variability in sleep onset for children. Lower mother’s education was associated with lower sleep efficiency. Children who attended Title 1 schools had shorter sleep minutes. Ethnicity was a significant moderator of effects in the link between some SES indicators and children’s sleep. AA children’s sleep was more negatively affected by income-to-needs ratio and mother’s education than was the sleep of EA children. Conclusions The results advocate for the importance of specifying particular SES and sleep variables used because they may affect the ability to detect associations between sleep and economic adversity. PMID:23148451

  13. Effects of lysine-induced acute renal failure in dogs.

    PubMed

    Asanuma, Kentaro; Adachi, Kenji; Sugimoto, Tetsuro; Chiba, Shuichi

    2006-05-01

    This study investigates the effects of lysine-induced acute renal failure. Female dogs received a lysine hydrochloride (lysine) of 4500 mg/kg/day (3.75 ml/kg/hr) for 3 consecutive days. The dogs were observed for clinical signs. Body weights were recorded, food consumption and water consumption calculated, and urinalysis and blood biochemistry were performed daily. Plasma samples for amino acid determinations were obtained from all dogs, which were necropsied on Day 3. Histopathological examinations were done on all test animals. Compound-related findings include the following. Blood biochemistry results showed increases in ammonia, blood urea nitrogen, blood urea nitrogen/creatinine ratio, and creatinine. Urinary changes consisted of increases in urine volume, total protein, albumin, gamma-glutamyl transpeptidase, and N-acetyl-beta-D-glucosaminidase. In addition, macroscopic findings consisted of pale, congested capsule; microscopic findings consisted of hypertrophy of proximal convoluted tubule (mainly S1 segment), and degeneration/desquamation of urinary tubule (mainly S3 segment with hyaline casts) in the kidney. From these findings, it can be concluded that lysine is nephrotoxic in dogs. Nephrotoxicity of lysine may relate to direct tubular toxicity and to tubular obstruction.

  14. Identifying adverse effects of area-based health policy: An ethnographic study of a deprived neighbourhood in England.

    PubMed

    Williams, Oli

    2017-03-17

    Health interventions commonly have adverse effects. Addressing these could significantly improve health outcomes. This paper addresses an adverse effect common in the promotion of health behaviours: exacerbation of health inequalities between low- and high-socioeconomic groups. Health behaviours - particularly, physical activity - are positioned within the context of social inequality and the inequitable spatial distribution of resources. Area-based health policy that targets deprived areas is assessed for its capacity to promote health behaviours without exacerbating inequality. Data are derived from a 16-month ethnography in a deprived English neighbourhood that was the target of area-based intervention that prioritised the promotion of physical activity. Findings provide evidence of adverse intervention effects that further disadvantaged the low-socioeconomic population. Analysis demonstrates how this was ultimately the outcome of localised policy drifting away from initial commitments to equitable service access. These findings increase understanding of the processes through which adverse intervention effects arise and how they can be mitigated.

  15. Developmental exposure to a mixture of two mechanistically distinct antiandrogens results in cumulative adverse reproductive effects in adult male rats

    EPA Science Inventory

    Typically, toxicological studies have focused on the adverse effects from exposure to single chemicals. However, endocrine disrupting chemicals (EDCs) are detected in the environment as mixtures. Empirical evidence suggests that mixtures of EDCs with the same mechanism of action...

  16. Effect of chronic antioxidant therapy with superoxide dismutase-mimetic drug, tempol, on progression of renal disease in rats with renal mass reduction.

    PubMed

    Quiroz, Yasmir; Ferrebuz, Atilio; Vaziri, Nosratola D; Rodriguez-Iturbe, Bernardo

    2009-01-01

    Oxidative stress and inflammation play a major role in the progression of renal damage and antioxidants are potentially useful therapeutic options in chronic renal disease. We investigated if treatment with tempol, a superoxide dismutase mimetic that has beneficial effects in several experimental models of hypertension and acute kidney injury, ameliorates the chronic renal damage resulting in renal mass reduction. Rats with surgical 5/6 nephrectomy were randomly assigned to receive no treatment (CRF group, n = 10) or tempol, 1 mmol/l in the drinking water (CRF-tempol group, n = 10). Sham-operated rats (n = 10) served as controls. All rats were followed for 12 weeks post-nephrectomy. Tempol treatment reduced plasma malondialdehyde (MDA) levels and halved the number of superoxide-positive cells in the remnant kidney; however, the number of hydrogen peroxide-positive cells increased and the overall renal oxidative stress (MDA and nitrotyrosine abundance) and inflammation (interstitial p65 NF-kappaB, macrophage and lymphocyte infiltration) were unchanged. Proteinuria, renal function and glomerular and tubulointerstitial damage in the remnant kidney were similar in the CRF and CRF-tempol groups. In conclusion, tempol administration, at the dose used in these studies, decreased plasma MDA and heightened superoxide dismutation in the kidney, but was incapable of reducing renal oxidative stress or improving renal function or structure in the remnant kidney model.

  17. PTH prevents the adverse effects of focal radiation on bone architecture in young rats

    PubMed Central

    Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Lin, Tiao; Zhang, Xianrong; Siclari, Valerie A.; Altman, Allison R.; Cengel, Keith A.; Liu, X. Sherry; Qin, Ling

    2013-01-01

    Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy. PMID:23466454

  18. Effect of nimodipine on systemic, renal, and cerebral haemodynamics after a mild hypoxic-ischaemic insult in newborn piglets.

    PubMed

    Raju, T N; John, E; Shankararao, R; Fornell, L; Vasa, R; Abu-Harb, M

    1996-01-01

    Because many Ca2+ channel blocking agents are known to cause adverse systemic effects, in this study we tested the haemodynamic side effects of nimodipine with and without a mild hypoxic-ischaemic (HI) insult in a newborn piglet model. Fifteen min after completing a brief period of asphyxia we gave i.v. nimodipine as 5 micrograms kg-1 bolus followed by 0.1 microgram kg-1 min-1 continuous infusion for 105 min in six piglets, while the same treatment was repeated in five animals without preceding HI insult. At third group of six served as sham operated controls. In the HI insult group by 105 min of nimodipine infusion the mean BP dropped by 30% and the cardiac output dropped by 23% of respective baseline. In this group, the renal blood flow dropped between 65% and 77% of baseline and regional cerebral blood flow dropped between 28% and 55% of respective baseline by 45 min and 105 min of nimodipine fashion. In the group with no prior HI insult, 105 min of nimodipine infusion caused no significant changes in these variables. Despite nimodipine infusion, HI insult caused a significant increase in the mean brain water content compared to the two control groups: 89 +/- 3.2% compared to 82.7 +/- 0.5% in the nimodipine control group, and 83.7 +/- 1.7% in the sham group (P < 0.0001). We conclude that while nimodipine therapy without prior asphyxial insult does not cause significant adverse haemodynamic effects, its infusion after even a mild HI insult could cause reduction in renal blood flow and moderate reduction in regional cerebral blood flow, BP, and cardiac output, suggesting a differential effect. A 15 min lag between HI insult and nimodipine therapy may be too long to prevent cerebral oedema.

  19. Effectiveness of theophylline prophylaxis of renal impairment after coronary angiography in patients with chronic renal insufficiency.

    PubMed

    Huber, Wolfgang; Schipek, Chrysantha; Ilgmann, Kathrin; Page, Michael; Hennig, Michael; Wacker, Annette; Schweigart, Ursula; Lutilsky, Leopoldo; Valina, Christian; Seyfarth, Melchior; Schömig, Albert; Classen, Meinhard

    2003-05-15

    Contrast media can lead to renal impairment that results in longer hospitalization and increased mortality. Adenosine is a crucial mediator of contrast-induced nephropathy (CIN; an increase in serum creatinine of >or=0.5 mg/dl within 48 hours). Therefore, it was the purpose of our study to investigate whether the adenosine antagonist theophylline reduces the incidence of CIN after coronary angiography. We also characterized risk factors for CIN after coronary angiography. One hundred patients with serum creatinine concentrations of >or=1.3 mg/dl randomly received 200 mg IV theophylline or placebo 30 minutes before coronary angiography (amount of contrast medium >or=100 ml). Patients who received theophylline and the controls were comparable with regard to baseline creatinine levels (means +/- SD) (1.65 +/- 0.41 vs 1.72 +/- 0.69 mg/dl) and the amount of contrast medium received (235 +/- 89 vs 261 +/- 139 ml). Theophylline significantly reduced the incidence of CIN (4% vs 20%, p = 0.0138). With placebo, creatinine significantly increased at 12 (1.82 +/- 0.79 mg/dl, p = 0.0057), 24 (1.90 +/- 0.86 mg/dl, p = 0.0001), and 48 hours (1.90 +/- 0.89 mg/dl, p = 0.0007) after administration of contrast medium. With pretreatment with theophylline, mean creatinine only increased 24 hours after contrast medium administration (1.70 +/- 0.40 mg/dl, p = 0.029), but was stable 12 hours (1.65 +/- 0.43 mg/dl, p = 0.99) and 48 hours after contrast medium administration (1.65 +/- 0.41 mg/dl, p = 0.99). The following parameters were significantly associated with contrast-induced renal impairment: Cigarroa quotient >5 (contrast medium [milliters] x serum creatinine/body weight [kg]), elevated troponin T, >300 ml of contrast medium, and emergency angiography. In conclusion, theophylline reduces the incidence of CIN in patients with chronic renal insufficiency undergoing coronary angiography. It should be used especially in patients receiving large amounts of contrast medium, and in

  20. Adverse effects of drug therapies on male and female sexual function.

    PubMed

    Stadler, Th; Bader, M; Uckert, S; Staehler, M; Becker, A; Stief, C G

    2006-12-01

    Sexual dysfunctions (SD) are adverse effects of common drug therapies that have rarely been considered in investigations so far. Possibly it is barely known that many widespread and frequently prescribed medications and drug therapies can have significant impact on vascular and nerval processes as well as on endocrinologic and psychoneuroendocrinologic systems and therefore can influence sexual functions. Impotence and disorders of the erectile function can mainly be caused by antidopaminergic mechanisms, whereas ejaculatory disorders and anorgasmia often can be explained by antiserotoninergic effects. Anticholinergic and adrenoloytic agents can also cause a particular impairment of erectile functions. The following considerations will show that the detection and treatment of SD (also in women!) should be given much more attention since drug-induced SDs occur predominantly in indications where a SD itself can be a symptom of the disease.

  1. Te Inclusions in CZT Detectors: New Method for Correcting Their Adverse Effects

    SciTech Connect

    Bolotnikov, A.E.; Babalola, S.; Camarda, G.S.; Cui, Y.; Egarievwe, S.U.; Hawrami, R.; Hossain, A.; Yang, G.; James, R.B.

    2009-10-25

    Both Te inclusions and point defects can trap the charge carriers generated by ionizing particles in CdZnTe (CZT) detectors. The amount of charge trapped by point defects is proportional to the carriers’ drift time and can be corrected electronically. In the case of Te inclusions, the charge loss depends upon their random locations with respect to the electron cloud. Consequently, inclusions introduce fluctuations in the charge signals, which cannot be easily corrected. In this paper, we describe direct measurements of the cumulative effect of Te inclusions and its influence on the response of CZT detectors of different thicknesses and different sizes and concentrations of Te inclusions. We also discuss a means of partially correcting their adverse effects.

  2. Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms

    PubMed Central

    Liu, Yonggang; Goodson, Jamie M.; Zhang, Bo; Chin, Michael T.

    2015-01-01

    Exposure to air pollution has long been known to trigger cardiovascular events, primarily through activation of local and systemic inflammatory pathways that affect the vasculature. Detrimental effects of air pollution exposure on heart failure and cardiac remodeling have also been described in human populations. Recent studies in both human subjects and animal models have provided insights into the basic physiological, cellular and molecular mechanisms that play a role in adverse cardiac remodeling. This review will give a brief overview of the relationship between air pollution and cardiovascular disease, describe the clinical effects of air pollution exposure on cardiac remodeling, describe the basic mechanisms that affect remodeling as described in human and animal systems and will discuss future areas of investigation. PMID:26042051

  3. Multiple sclerosis disease-modifying therapies: adverse effect surveillance and management.

    PubMed

    Wingerchuk, Dean M

    2006-03-01

    There are five approved, partially effective, parenteral disease-modifying therapies for multiple sclerosis (MS), including three interferon-beta preparations, glatiramer acetate and the antineoplastic agent mitoxantrone. A sixth drug, natalizumab, was withdrawn from the market in 2005 but could return with increased safety measures. Careful surveillance for, and management of, the minor and serious adverse effects associated with these therapies in routine practice provides the best opportunity for maintaining compliance and achieving maximal therapeutic efficacy. This review outlines the strategies for the prevention, identification and management of the complications associated with administration and ongoing use of current MS therapies. These skills will become increasingly important to those caring for MS patients as contemporary treatment regimens become increasingly complex.

  4. Oral Bisphosphonate Related Osteonecrosis of the Jaw: A Challenging Adverse Effect

    PubMed Central

    2013-01-01

    Oral bisphosphonates are the most commonly prescribed antiresorptive drugs for the treatment of osteoporosis. However, there are several adverse effects associated with oral bisphosphonates including the bisphosphonate related osteonecrosis of the jaw (BRONJ). With a better understanding of this side effect, reported incidences for BRONJ in oral bisphosphonate users have increased in time. The pathogenesis of BRONJ has not been well determined. Several risk factors such as dentoalveolar surgery, therapy duration, and concomitant steroid usage have been linked to BRONJ. Conservative and surgical methods can be preferred in the treatment. Preventative measures are of great importance for the patients at high risk. In this paper, osteonecrosis of the jaw secondary to oral bisphosphonates was reviewed in order to increase awareness as well as to renew the current knowledge. PMID:23762600

  5. Human exposure to mercury: A critical assessment of the evidence of adverse health effects

    SciTech Connect

    Ratcliffe, H.E.; Swanson, G.M.; Fischer, L.J.

    1996-10-25

    The ubiquitous nature of mercury in the environment, its global atmospheric cycling, and its toxicity to humans at levels that are uncomfortably close to exposures experienced by a proportion of the population are some of the current concerns associated with this pollutant. The purpose of this review is to critically evaluate the scientific quality of published reports involving human exposures to mercury and associated health outcomes as an aid in the risk evaluation of this chemical. A comprehensive review of the scientific literature involving human exposures to mercury was performed and each publication evaluated using a defined set of criteria that are considered standards in epidemiologic and toxicologic research. Severe, sometimes fatal, effects of mercury exposure at high levels were primarily reported as case studies. The disasters in Minamata, Japan, in the 1950s and in Iraq in 1971-1972 clearly demonstrated neurologic effects associated with ingestion of methylmercury both in adults and in infants exposed in utero. The effects were convincingly Associated with methylmercury ingestion, despite limitations of the study design. Several well-conducted studies have investigated the effects of methylmercury at levels below those in the Iraq incident but have not provided clear evidence of an effect. The lower end of the dose-response curve constructed from the Iraq data therefore still needs to be confirmed. The studies of mercury exposure in the workplace were mainly of elemental or inorganic mercury, and effects that were observed at relatively low exposure levels were primarily neurologic and renal. Several studies have investigated effects associated with dental amalgam but have been rated as inconclusive because of methodologic deficiencies. In our overall evaluation, 29 of 110 occupational studies and 20 of 54 studies where exposure occurred in the natural environment provided at least suggestive evidence of an exposure-related effect. 259 refs., 4 tabs.

  6. Review for carrageenan-based pharmaceutical biomaterials: favourable physical features versus adverse biological effects.

    PubMed

    Liu, Jingjing; Zhan, Xiudan; Wan, Jianbo; Wang, Yitao; Wang, Chunming

    2015-05-05

    Carrageenan (CRG) is a family of natural polysaccharides derived from seaweeds and has widely been used as food additives. In the past decade, owing to its attractive physicochemical properties, CRG has been developed into versatile biomaterials vehicles for drug delivery. Nevertheless, studies also emerged to reveal its adverse effects on the biological system. In this review, we critically appraise the latest literature (two thirds since 2008) on the development of CRG-based pharmaceutical vehicles and the perspective of using CRG for broader biomedical applications. We focus on how current strategies exploit the unique gelling mechanisms, strong water absorption and abundant functional groups of the three major CRG varieties. Notably, CRG-based matrices are demonstrated to increase drug loading and drug solubility, enabling release of orally administrated drugs in zero-order or in a significantly prolonged period. Other amazing features, such as pH-sensitivity and adhesive property, of CRG-based formulations are also introduced. Finally, we discuss the adverse influence of CRG on the human body and then suggest some future directions for the development of CRG-based biomaterials for broader applications in biomedicine.

  7. Duration of Internet use and adverse psychosocial effects among European adolescents.

    PubMed

    Secades-Villa, Roberto; Calafat, Amador; Fernández-Hermida, José Ramón; Juan, Montse; Duch, Mariangels; Skärstrand, Eva; Becoña, Elisardo; Talic, Sanela

    2014-01-01

    Despite the significant contributions from previous studies about the prevalence of problematic Internet use (PIU) among adolescents in Europe, important questions remain regarding adverse consequences of PIU. This study aims to assess the relation between duration of Internet use and adverse psychosocial effects among adolescents from six European countries. The final sample included 7,351 adolescents (50.8% male and 49.2% female; mean age: 14.6±1.90) recruited from randomly selected schools within the six study sites. Results showed that 12.9% of adolescents used Internet more than 20 hours per week. There was a significant relationship between duration of Internet use and frequency of alcohol, tobacco, cannabis and other illegal drug use. Duration of Internet use is also significantly associated with school problems, with use of slot machines and with other psychosocial problems. These findings highlight the need to strengthen preventive efforts for reducing PIU and related consequences among adolescents. Key Words: Internet, adolescents, psychosocial problems.

  8. PERSYVE - Design and validation of a questionnaire about adverse effects of antihypertensive drugs

    PubMed Central

    Duarte-Silva, Daniela; Figueiras, Adolfo; Herdeiro, Maria T.; Teixeira Rodrigues, António; Silva Branco, Fábio; Polónia, Jorge; Figueiredo, Isabel V.

    2013-01-01

    Objective The aim of this study was to design and validate a questionnaire to measure perceived symptoms associated with antihypertensive drugs (PERSYVE). Methods The PERSYVE development and validation included four stages: 1) item development (bibliographic review and questionnaire elaboration); 2) face and content validation; 3) field testing (pre-test); and 4) test-retest validation, assessment of internal consistency (Cronbach’s alpha) and reproducibility over time (intraclass correlation coefficient and Cohen’s kappa coefficient). Results PERSYVE is divided into six sections according to results obtained from the literature review: (1) drug adherence, (2) perceived symptoms and how they affect quality of life (five-point Likert scale), (3) communication with health professionals, (4) perception of symptoms as adverse reactions, (5) influence on therapy compliance, and (6) adoption of non-pharmacological methods for blood pressure control. Content and face validation of the questionnaire led to some vocabulary changes and the introduction of section 2.1. Field-testing (n=26) revealed high comprehensibility of the questions. The Cronbach's alpha, calculated for section 2 (five-point Likert scale) was 0.850. PERSYVE was reproducible (n=167): kappa values presented fair to substantial reproducibility and, in section 2, ICC values resulted in good to excellent reproducibility. Conclusion Results showed that PERSYVE is a well-structured, objective, patient-friendly, valid and reliable questionnaire. PERSYVE can be a very useful instrument in hypertensive patients’ monitoring and in the screening of adverse effects. PMID:25035716

  9. Effects of 6 months yoga program on renal functions and quality of life in patients suffering from chronic kidney disease

    PubMed Central

    Pandey, Rajendra Kumar; Arya, Tung Vir Singh; Kumar, Amit; Yadav, Ashish

    2017-01-01

    Aim: To study the effect of 6 months yoga program in patients suffering from chronic kidney disease (CKD). Materials and Methods: Fifty-four patients with CKD were studied and divided into two groups (yoga group and control group) to see the effect of yoga in CKD. Patients in the yoga group were offered yoga therapy along with other conventional treatment modalities, while the control group was only on conventional treatment. Subjects in yoga group were trained to perform specific yogic asanas for at least 5 days a week for 40–60 min a day. Regular monitoring of blood pressure, renal function, requirement of a number of dialysis, and quality of life (QOL) indicators were done. Fifty patients (yoga – 25; control-25) completed 6 months follow-up. Results: In yoga group, a significant reduction of systolic and diastolic blood pressure, significant reduction in blood urea and serum creatinine levels, and significant improvement in physical and psychological domain of the World Health Organization QOL (as assessed by BREF QOL scores) were seen after 6 months. In control group, rise of blood pressure, deterioration of renal function, and QOL were observed. Poststudy comparison between the two groups showed a statistically significant reduction of blood pressure, nonsignificant reduction in blood urea and serum creatinine, and significant improvement in physical and psychological domain of QOL in yoga group as compared to control group. For subjects in yoga group, the need for dialysis was less when compared to control group although this difference was statistically insignificant. Except for inability of some patients to perform certain yogic asanas no adverse effect was found in the study. Conclusion: Six months yoga program is safe and effective as an adjuvant therapy in improving renal functions and QOL of CKD patients. PMID:28149061

  10. Effect of percutaneous renal sympathetic nerve radiofrequency ablation in patients with severe heart failure.

    PubMed

    Dai, Qiming; Lu, Jing; Wang, Benwen; Ma, Genshan

    2015-01-01

    This study aimed to investigate the clinical feasibility and effects of percutaneous renal sympathetic nerve radiofrequency ablation in patients with heart failure. A total of 20 patients with heart failure were enrolled, aged from 47 to 75 years (63±10 years). They were divided into the standard therapy (n = 10), and renal nerve radiofrequency ablation groups (n = 10). There were 15 males and 5 female patients, including 8 ischemic cardiomyopathy, 8 dilated cardiomyopathy, and 8 hypertensive cardiopathy. All of the patients met the criteria of New York Heart Association classes III-IV cardiac function. Patients with diabetes and renal failure were excluded. Percutaneous renal sympathetic nerve radiofrequency ablation was performed on the renal artery wall under X-ray guidance. Serum electrolytes, neurohormones, and 24 h urine volume were recorded 24 h before and after the operation. Echocardiograms were performed to obtain left ventricular ejection fraction at baseline and 6 months. Heart rate, blood pressure, symptoms of dyspnea and edema were also monitored. After renal nerve ablation, 24 h urine volume was increased, while neurohormone levels were decreased compared with those of pre-operation and standard therapy. No obvious change in heart rate or blood pressure was recorded. Symptoms of heart failure were improved in patients after the operation. No complications were recorded in the study. Percutaneous renal sympathetic nerve radiofrequency ablation may be a feasible, safe, and effective treatment for the patients with severe congestive heart failure.

  11. Protective effects of icariin on cisplatin-induced acute renal injury in mice

    PubMed Central

    Ma, Pei; Zhang, Sen; Su, Xinlin; Qiu, Guixing; Wu, Zhihong

    2015-01-01

    Cisplatin chemotherapy often causes acute kidney injury in cancer patients. Icariin is a bioactive flavonoid, which has renal protection and anti-inflammation effects. This study investigated the mechanism underlying the attenuation of cisplatin-induced renal injury by icariin. BALB/c mice were treated with cisplatin (15 mg/kg) with or without treatment with icariin (30 or 60 mg/kg for 5 days). Renal function, histological changes, degree of oxidative stress and tubular apoptosis were examined. The effects of icariin on cisplatin-induced expression of renal TNF-α, NF-κB, cleaved caspase-3 and Bcl-2 family proteins were evaluated. Treatment of mice with cisplatin resulted in renal damage, showing an increase in blood urea nitrogen and creatinine levels, tubular damage, oxidative stress and apoptosis. These renal changes could be significantly improved by icariin treatment, especially in high dose of icariin group. Examination of molecules involving inflammation and apoptosis of the kidney revealed that treatment of icariin reduced expression of TNF-α, NF-κB, cleaved caspase-3, and Bax, increased the expression of BCL-2. These results indicate that icariin ameliorates the cisplatin-mediated nephrotoxicity via improving renal oxidant status, consequent NF-κB activation and inflammation cascade and apoptosis, and the following disturbed expression of apoptosis related proteins. PMID:26692955

  12. Renal hemodynamic effects of nabumetone, sulindac, and placebo in patients with osteoarthritis.

    PubMed

    Cangiano, J L; Figueroa, J; Palmer, R

    1999-03-01

    We assessed the effects of nabumetone, sulindac, and placebo on renal function and renal excretion of vasodilatory prostaglandins in older female patients (age >50 years) with osteoarthritis and normal renal function. Using a prospective, crossover design, we compared the effects of nabumetone 2000 mg/d and sulindac 400 mg/d with placebo on glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary excretion of prostaglandin E2 and 6-keto-prostaglandin F1alpha in 12 patients. Urinary excretion of vasodilatory prostaglandins was not decreased after 14 days of treatment with either nabumetone or sulindac. Likewise, treatment with nabumetone or sulindac did not significantly alter renal function compared with placebo. There were no differences in mean changes in GFR or RPF from baseline after treatment with nabumetone or sulindac compared with placebo. The mean (+/- SD) changes in GFR from baseline were 0%+/-8% in patients receiving nabumetone, -8%+/-15% in patients receiving sulindac, and -7%+/-15% in patients receiving placebo. The results of this study demonstrate that treatment with nabumetone or sulindac caused no deterioration in renal function in older female patients with osteoarthritis and normal renal function.

  13. Mediators and Adverse Effects of Child Poverty in the United States.

    PubMed

    Pascoe, John M; Wood, David L; Duffee, James H; Kuo, Alice

    2016-04-01

    The link between poverty and children's health is well recognized. Even temporary poverty may have an adverse effect on children's health, and data consistently support the observation that poverty in childhood continues to have a negative effect on health into adulthood. In addition to childhood morbidity being related to child poverty, epidemiologic studies have documented a mortality gradient for children aged 1 to 15 years (and adults), with poor children experiencing a higher mortality rate than children from higher-income families. The global great recession is only now very slowly abating for millions of America's children and their families. At this difficult time in the history of our nation's families and immediately after the 50th anniversary year of President Lyndon Johnson's War on Poverty, it is particularly germane for the American Academy of Pediatrics, which is "dedicated to the health of all children," to publish a research-supported technical report that examines the mediators associated with the long-recognized adverse effects of child poverty on children and their families. This technical report draws on research from a number of disciplines, including physiology, sociology, psychology, economics, and epidemiology, to describe the present state of knowledge regarding poverty's negative impact on children's health and development. Children inherit not only their parents' genes but also the family ecology and its social milieu. Thus, parenting skills, housing, neighborhood, schools, and other factors (eg, medical care) all have complex relations to each other and influence how each child's genetic canvas is expressed. Accompanying this technical report is a policy statement that describes specific actions that pediatricians and other child advocates can take to attenuate the negative effects of the mediators identified in this technical report and improve the well-being of our nation's children and their families.

  14. Adverse Effects of Osteocytic Constitutive Activation of ß-Catenin on Bone Strength and Bone Growth.

    PubMed

    Chen, Sixu; Feng, Jianquan; Bao, Quanwei; Li, Ang; Zhang, Bo; Shen, Yue; Zhao, Yufeng; Guo, Qingshan; Jing, Junjun; Lin, Shuxian; Zong, Zhaowen

    2015-07-01

    The activation of the canonical Wnt/β-catenin signaling pathway in both mesenchymal stem cells and osteoblasts has been demonstrated to increase bone mass, showing promise for the treatment of low bone volume conditions such as osteoporosis. However, the possible side effects of manipulating this pathway have not been fully addressed. Previously, we reported that the constitutive activation of ß-catenin in osteoblasts impaired vertebral linear growth. In the present study, β-catenin was constitutively activated in osteocytes by crossing Catnb+/lox(exon 3) mice with dentin matrix protein 1(DMP1)-Cre transgenic mice, and the effects of this activation on bone mass, bone growth and bone strength were then observed. DMP1-Cre was found to be predominantly expressed in osteocytes, with weak expression in a small portion of osteoblasts and growth plate chondrocytes. After the activation, the cancellous bone mass was dramatically increased, almost filling the entire bone marrow cavity in long bones. However, bone strength decreased significantly. Thinner and more porous cortical bone along with impaired mineralization were responsible for the decrease in bone strength. Furthermore, the mice showed shorter stature with impaired linear growth of the long bones. Moreover, the concentration of serum phosphate decreased significantly after the activation of ß-catenin, and a high inorganic phosphate (Pi) diet could partially rescue the phenotype of decreased mineralization level and impaired linear growth. Taken together, the constitutive activation of β-catenin in osteocytes may increase cancellous bone mass; however, the activation also had adverse effects on bone strength and bone growth. These adverse effects should be addressed before the adoption of any therapeutic clinical application involving adjustment of the Wnt/β-catenin signaling pathway.

  15. Effects of Sugammadex and Neostigmine on Renal Biomarkers

    PubMed Central

    Isik, Yasemin; Palabiyik, Onur; Cegin, Bilal Muhammed; Goktas, Ugur; Kati, Ismail

    2016-01-01

    Background Neostigmine, the currently commonly used agent for reversal of neuromuscular blockade. Sugammadex is a novel and unique compound designed as an antagonist of steroidal neuromuscular blockers. In this study, we evaluated the effects of sugammadex or neostigmine on kidney functions in patients scheduled for elective surgery. Material/Methods Patients scheduled for a surgical procedure under desflurane/opioid anesthesia received an intubating dose rocuronium. Patients were divided into 2 groups receiving either sugammadex or neostigmine atropine to reverse neuromuscular blockade. Cystatin C, creatinine, urea, blood urea nitrogen, sodium, potassium, and calcium levels in the blood and α1microglobulin, β2microglobulin, and microalbumin levels in the urine were measured. Results There was no significant difference between the groups with regard to the demographic data. In the Neostigmine Group, although β2microglobulin and microalbumin were similar, a significant increase was found in the postoperative α1microglobulin and cystatin C values. In the Sugammadex Group, although β2-microglobulin and cystatin C were similar, a significant increase was found in the postoperative α1-microglobulin and microalbumin values. The only significant difference was cystatin C value variation in the Neostigmine Group compared to the Sugammadex Group. Conclusions We believe that the use of more specific and sensitive new-generation markers like cystatin C to evaluate kidney function will provide a better understanding and interpretation of our results. Sugammadex has more tolerable effects on kidney function in patients than does neostigmine. However, when compared to preoperative values, there is a negative alteration of postoperative values. Neostigmine and sugammadex do not cause renal failure but they may affect kidney function. PMID:26963316

  16. Effects of acute hepatic and renal failure on pharmacokinetics of flunixin meglumine in rats.

    PubMed

    Hwang, Youn-Hwan; Yun, Hyo-In

    2011-01-01

    The aim of this study was to investigate the effects of hepatic and renal failure on the pharmacokinetics of flunixin in carbon tetrachloride (CCl(4))- and glycerol-treated rats. After intravenous administration of flunixin (2 mg/kg), the plasma concentration of flunixin was measured by high-performance liquid chromatography. Both acute hepatic and renal failure resulted in significantly increased area under the curve (AUC), prolonged elimination half-life (t(1/2β)), and reduced total body clearance (Cl(tot)) compared with respective controls (P<0.05). In conclusion, hepatic failure as well as renal failure modified the pharmacokinetics of flunixin.

  17. Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports.

    PubMed

    Lake, C R; Gallant, S; Masson, E; Miller, P

    1990-08-01

    Phenylpropanolamine (PPA) is contained in about 106 products, over half of which are available over-the-counter (OTC). Most are cough/cold remedies; nine are OTC diet aids. More than nine million Americans were using OTC diet aids in 1981, making PPA the fifth most used drug in the United States, responsible for over $200 million in revenues. The safety of PPA remains controversial. Although most controlled studies indicate minimal pressor effects with recommended doses, adverse drug reactions (ADRs) continue to be documented. Since 1965, 142 ADRs have been reported in 85 studies, 69% of these in North America. Many such cases may go unrecognized. About two thirds of all ADRs occurred in females and in patients under 30. Of ADRs attributed to legitimately sold PPA products, 85% occurred after consumption of OTC products versus only 15% after prescription drugs. The PPA product often contained combination ingredients, or PPA was consumed along with additional drugs. An overdose of PPA was taken in about a third of the cases. After ingestion of non-overdose amounts, 82% of the ADRs were severe. The most frequent side effects involved symptoms compatible with acute hypertension, with severe headache the most common complaint. Twenty-four intracranial hemorrhages, eight seizures, and eight deaths (most due to stroke) were associated with PPA ingestion. We have summarized these data in an effort to alert clinicians to the prevalence of usage of PPA products and the potential for adverse effects. In patients who present with elevated blood pressure or signs of acute hypertension, especially hypertensive encephalopathy of undetermined origin, we recommend inquiry about recent ingestion of PPA-containing diet aids and cough/cold products and suggest having such patients remain upright rather than supine.

  18. Therapeutic and adverse effects of flunixin-meglumine in adult and young cats.

    PubMed

    Takata, Kenji; Hikasa, Yoshiaki; Satoh, Hiroshi

    2011-12-01

    In this study, we elucidated the difference in nonsteroidal anti-inflammatory drug sensitivities between young and adult cats on therapeutic and adverse effects. In the prevention of lipopolysaccharide (LPS)-induced hyperthermia using flunixin-meglumine, young (<3 months old) and adult (>12 months old) cats of both sexes were given LPS (0.3 µg/kg, i.v.), and body temperature was measured 24 hr later. Flunixin (1 mg/kg, s.c.) was administered 30 min before the LPS injection. LPS-induced hyperthermia was almost completely inhibited by pre-treatment with flunixin in both adult and young cats. In addition, flunixin showed almost the same antipyretic effects in both young and adult cats. The animals were administered flunixin (1 mg/kg, s.c.) once a day for 3 days, and sacrificed 24 hr later to examine the gastrointestinal mucosal lesions. In adult cats, flunixin caused many severe lesions in the small intestine. In contrast, very few gastrointestinal lesions were produced by flunixin in young cats. In the pharmacokinetics of flunixin, plasma concentrations of flunixin were analysed using a high performance liquid chromatography. There were no significant differences in plasma concentration of flunixin between young and adult cats from 0.5 to 4 hr after the injection. These results demonstrated that NSAIDs could be used more safely in young than in adult cats from the points of gastrointestinal adverse effects. Furthermore, this difference in gastrointestinal lesions between adult and young cats was not related with the plasma concentration of flunixin.

  19. Ground experiments for finding principles and working out methods for preventing adverse effects of weightlessness on the human organism

    NASA Technical Reports Server (NTRS)

    Kakurin, L. I.; Gregoryev, A. I.; Mikhailov, V. M.; Tishler, V. A.

    1980-01-01

    A comparative assessment of the effectiveness of different prophylactic procedures to prevent the adverse effects of weightlessness is presented. It is concluded that: physical training is most effective but no single method by itself produces the full effect, and an adjustment of regimes to one another enhances the effect. The approved complex of prophylactic procedures affected basic changes occurring in hypokinesia: deficit of muscular activity, no or reduced BP hydrostatic component, reduced volume of blood circulation, reduced hydration level, and the application of various prophylactic complexes during 49 day antiorthostatic hypodynamia eliminated or reduced the adverse effects of weightlessness in simulation.

  20. An in-flight simulation of approach and landing of a STOL transport with adverse ground effect

    NASA Technical Reports Server (NTRS)

    Ellis, D. R.

    1976-01-01

    The results of an in-flight simulation program undertaken to study the problems of landing a representative STOL transport in the presence of adverse ground effects are presented. Landings were performed with variations in ground effect magnitude, ground effect lag, and thrust response. Other variations covered the effects of augmented lift response, SAS-failures, turbulence, segmented approach, and flare warning. The basic STOL airplane required coordinated use of both stick and throttle for consistently acceptable landings, and the presence of adverse ground effects made the task significantly more difficult. Ground effect lag and good engine response gave noticeable improvement, as did augmented lift response.

  1. Diverse Effects on M1 Signaling and Adverse Effect Liability within a Series of M1 Ago-PAMs.

    PubMed

    Rook, Jerri M; Abe, Masahito; Cho, Hyekyung P; Nance, Kellie D; Luscombe, Vincent B; Adams, Jeffrey J; Dickerson, Jonathan W; Remke, Daniel H; Garcia-Barrantes, Pedro M; Engers, Darren W; Engers, Julie L; Chang, Sichen; Foster, Jarrett J; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Conn, P Jeffrey; Lindsley, Craig W

    2017-01-10

    Both historical clinical and recent preclinical data suggest that the M1 muscarinic acetylcholine receptor is an exciting target for the treatment of Alzheimer's disease and the cognitive and negative symptom clusters in schizophrenia; however, early drug discovery efforts targeting the orthosteric binding site have failed to afford selective M1 activation. Efforts then shifted to focus on selective activation of M1 via either allosteric agonists or positive allosteric modulators (PAMs). While M1 PAMs have robust efficacy in rodent models, some chemotypes can induce cholinergic adverse effects (AEs) that could limit their clinical utility. Here, we report studies aimed at understanding the subtle structural and pharmacological nuances that differentiate efficacy from adverse effect liability within an indole-based series of M1 ago-PAMs. Our data demonstrate that closely related M1 PAMs can display striking differences in their in vivo activities, especially their propensities to induce adverse effects. We report the discovery of a novel PAM in this series that is devoid of observable adverse effect liability. Interestingly, the molecular pharmacology profile of this novel PAM is similar to that of a representative M1 PAM that induces severe AEs. For instance, both compounds are potent ago-PAMs that demonstrate significant interaction with the orthosteric site (either bitopic or negative cooperativity). However, there are subtle differences in efficacies of the compounds at potentiating M1 responses, agonist potencies, and abilities to induce receptor internalization. While these differences may contribute to the differential in vivo profiles of these compounds, the in vitro differences are relatively subtle and highlight the complexities of allosteric modulators and the need to focus on in vivo phenotypic screening to identify safe and effective M1 PAMs.

  2. Pulmonary aspergilloma with renal oxalosis: fatal effect at a distance.

    PubMed

    Vaideeswar, Pradeep; Sakhdeo, Uma M

    2009-05-01

    Some species of the fungus Aspergillus, especially Aspergillus niger, produce oxalic acid as a fermentation byproduct. The acid combines with calcium ions at physiological pH to form insoluble calcium oxalate crystals that are mainly deposited at local sites. This is often seen in the lungs, where the crystals tend to potentiate the destructive capacity of the fungus. In rare instances, there is hyperoxaluria and deposition of the crystals in the renal tubules. We report this rare occurrence in a 59-year-old man with pulmonary aspergilloma and acute renal failure. To the best of our knowledge, this is the fifth case to be reported.

  3. The Combined Effect of High Ambient Temperature and Antihypertensive Treatment on Renal Function in Hospitalized Elderly Patients

    PubMed Central

    Novack, Victor; Rogachev, Boris; Haviv, Yosef S.; Barski, Leonid

    2016-01-01

    Background The aging kidney manifests structural, functional as well as pharmacological changes, rendering elderly patients more susceptible to adverse environmental influences on their health, dehydration in particular. Hypothesis Higher temperature is associated with renal function impairment in patients 65 years and older who routinely take thiazide and/or ACE-inhibitors/ARBs. Methods We obtained health data of patients older than 65 who were admitted to a large tertiary center during the years 2006–2011, with a previous diagnosis of hypertension, and treated with thiazide, ACE-inhibitors/ARBs or both. We collected environmental data of daily temperature, available from collaborative public and governmental institutions. In order to estimate the effect of daily temperature on renal function we performed linear mixed models, separately for each treatment group and creatinine change during hospital admission. Results We identified 26,286 admissions for 14, 268 patients with a mean age of 75.6 (±6.9) years, of whom 53.6% were men. Increment in daily temperature on admission of 5°C had significant effect on creatinine increase in the no treatment (baseline creatinine adjusted 0.824 mg/dL, % change 1.212, % change 95% C.I 0.082–2.354) and dual treatment groups (baseline creatinine adjusted 1.032mg/dL, % change 3.440, % change 95% C.I 1.227–5.700). Sub-analysis stratified by advanced age, chronic kidney disease and primary diagnosis on hospital admission, revealed a significant association within patients admitted due to acute infection and treated with dual therapy. Conclusion Whereas previous studies analyzed sporadic climate effects during heat waves and/or excluded older population taking anti-hypertensive medications, the present study is novel by showing a durable association of temperature and decreased renal function specifically in elderly patients taking anti-hypertensive medications. PMID:27992525

  4. Renal Protective Effects of 17β-Estradiol on Mice with Acute Aristolochic Acid Nephropathy.

    PubMed

    Shi, Min; Ma, Liang; Zhou, Li; Fu, Ping

    2016-10-18

    Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs) characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2) was found to attenuate renal ischemia-reperfusion injury. Thus, the aim of this study was to investigate the potential protective role of E2 in acute AAN. Compared with male C57BL/6 mice of acute AAN, lower serum creatinine (SCr) and less renal injury, together with RTEC apoptosis in females, were found. Treatment with E2 in male AAN mice reduced SCr levels and attenuated renal tubular injury and RTEC apoptosis. In the mice kidney tissue and human renal proximal tubule cells (HK-2 cells), E2 both attenuated AA-induced cell apoptosis and downregulated the expression of phosphor-p53 (Ser15), p53, and cleaved-caspase-3. This study highlights that E2 exhibited protective effects on the renal injury of acute AAN in male mice by reducing RTEC apoptosis, which might be related to inhibiting the p53 signaling pathway.

  5. Do shrubs reduce the adverse effects of grazing on soil properties?

    USGS Publications Warehouse

    Eldridge, David J.; Beecham, Genevieve; Grace, James B.

    2015-01-01

    Increases in the density of woody plants are a global phenomenon in drylands, and large aggregations of shrubs, in particular, are regarded as being indicative of dysfunctional ecosystems. There is increasing evidence that overgrazing by livestock reduces ecosystem functions in shrublands, but that shrubs may buffer the negative effects of increasing grazing. We examined changes in water infiltration and nutrient concentrations in soils under shrubs and in their interspaces in shrublands in eastern Australia that varied in the intensity of livestock grazing. We used structural equation modelling to test whether shrubs might reduce the negative effects of overgrazing on infiltration and soil carbon and nitrogen (henceforth ‘soil nutrients’). Soils under shrubs and subject to low levels of grazing were more stable and had greater levels of soil nutrients. Shrubs had a direct positive effect on soil nutrients; but, grazing negatively affected nutrients by increasing soil bulk density. Structural equation modelling showed that shrubs had a direct positive effect on water flow under ponded conditions but also enhanced water flow, indirectly, through increased litter cover. Any positive effects of shrubs on water flow under low levels of grazing waned at high levels of grazing. Our results indicate that shrubs may reduce the adverse effects of grazing on soil properties. Specifically, shrubs could restrict access to livestock and therefore protect soils and plants beneath their canopies. Low levels of grazing are likely to ensure the retention of soil water and soil carbon and nitrogen in shrubland soils.

  6. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal

    PubMed Central

    2016-01-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012–2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  7. Evidence for the adverse effect of starvation on bone quality: a review of the literature.

    PubMed

    Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

    2015-01-01

    Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality.

  8. CORAL: binary classifications (active/inactive) for Liver-Related Adverse Effects of Drugs.

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Rasulev, Bakhtiyor F; Benfenati, Emilio; Gini, Giuseppina; Leszczynska, Danuta; Leszczynski, Jerzy

    2012-09-01

    Classification data related to the Liver-Related Adverse Effects of Drugs have been studied with the CORAL software (http://www.insilico.eu/coral). Two datasets which contain compounds with two serum enzyme markers of liver toxicity: alanine aminotransferase (ALT, n=187) and aspartate aminotransferase (AST, n=209) are analyzed. Statistical quality of the prediction for ALT activity is n=35, Sensitivity = 0.5556, Specificity = 0.8077, and Accuracy = 0.7429. In the case of AST activity the prediction is characterized by n=42, Sensitivity = 0.6875, Specificity = 0.7692, and Accuracy = 0.7381. A number of structural alerts which can be related to the studied activities are revealed. It is the first attempt to build up the classification QSAR model by means of the Monte Carlo technique based on representation of the molecular structure by SMILES using the CORAL software.

  9. Propolis: a review of properties, applications, chemical composition, contact allergy, and other adverse effects.

    PubMed

    de Groot, Anton C

    2013-01-01

    Propolis (bee glue) is the resinous substance that bees collect from living plants for the construction and adaptation of their nests. It has antibacterial, antifungal, and antiviral properties and may have a wide range of other beneficial biological activities. Propolis is available as a dietary supplement, in products for the protection of health and prevention of diseases, in biopharmaceuticals, and as a constituent of (bio)cosmetics. In this article, the following aspects of propolis are reviewed: the nature and chemical composition, its biological properties and applications, contact allergy and allergic contact dermatitis (sensitizing potential, products causing contact allergy, clinical picture, frequency of sensitization, coreactivity and cross-reactivity, the allergens in propolis), and other adverse effects.

  10. Diagnostic criteria for adverse health effects in the environs of wind turbines.

    PubMed

    McMurtry, Robert Y; Krogh, Carmen Me

    2014-10-01

    In an effort to address climate change, governments have pursued policies that seek to reduce greenhouse gases. Alternative energy, including wind power, has been proposed by some as the preferred approach. Few would debate the need to reduce air pollution, but the means of achieving this reduction is important not only for efficiency but also for health protection. The topic of adverse health effects in the environs of industrial wind turbines (AHE/IWT) has proven to be controversial and can present physicians with challenges regarding the management of an exposure to IWT. Rural physicians in particular must be aware of the possibility of people presenting to their practices with a variety of sometimes confusing complaints. An earlier version of the diagnostic criteria for AHE/IWT was published in August 2011. A revised case definition and a model for a study to establish a confirmed diagnosis is proposed.

  11. Diagnostic criteria for adverse health effects in the environs of wind turbines

    PubMed Central

    Krogh, Carmen ME

    2014-01-01

    Summary In an effort to address climate change, governments have pursued policies that seek to reduce greenhouse gases. Alternative energy, including wind power, has been proposed by some as the preferred approach. Few would debate the need to reduce air pollution, but the means of achieving this reduction is important not only for efficiency but also for health protection. The topic of adverse health effects in the environs of industrial wind turbines (AHE/IWT) has proven to be controversial and can present physicians with challenges regarding the management of an exposure to IWT. Rural physicians in particular must be aware of the possibility of people presenting to their practices with a variety of sometimes confusing complaints. An earlier version of the diagnostic criteria for AHE/IWT was published in August 2011. A revised case definition and a model for a study to establish a confirmed diagnosis is proposed. PMID:25383200

  12. The forensic nursing in sexual assaults: the immunochemical diagnosis and prevention of its adverse effects.

    PubMed

    Vitale, Elsa

    2012-04-01

    Sexual assault was a ubiquitous and serious problem in our society. The world's care centers and forensic associations, which were at the forefront of scientific research in sexual assaults, discussed the role of the Forensic Nursing in their early diagnosis and their prevention, but little has been written in literature regarding their appropriate management. This article focuses on the immunochemical laboratory investigation in diagnosis and prevention of its adverse effects in sexual assaults and the role of the Forensic Nursing played in this task. After a careful reading of all the material received from many of the care centers and the associations contacted, a Forensic Nursing Examination Program, with specific immunochemical address, is identified.

  13. Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

    PubMed Central

    Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E.

    2015-01-01

    Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

  14. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

    SciTech Connect

    Spino, M.; Chai, R.P.; Isles, A.F.; Balfe, J.W.; Brown, R.G.; Thiessen, J.J.; MacLeod, S.M.

    1985-07-01

    A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and /sup 125/I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the result of enhanced glomerular filtration or tubular secretion.

  15. Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery.

    PubMed

    Savulich, G; Riccelli, R; Passamonti, L; Correia, M; Deakin, J F W; Elliott, R; Flechais, R S A; Lingford-Hughes, A R; McGonigle, J; Murphy, A; Nutt, D J; Orban, C; Paterson, L M; Reed, L J; Smith, D G; Suckling, J; Tait, R; Taylor, E M; Sahakian, B J; Robbins, T W; Ersche, K D

    2017-03-07

    Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.

  16. Metabolically normal obese people are protected from adverse effects following weight gain.

    PubMed

    Fabbrini, Elisa; Yoshino, Jun; Yoshino, Mihoko; Magkos, Faidon; Tiemann Luecking, Courtney; Samovski, Dmitri; Fraterrigo, Gemma; Okunade, Adewole L; Patterson, Bruce W; Klein, Samuel

    2015-02-01

    BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as "metabolically normal obese" (MNO), but not those defined as "metabolically abnormal obese" (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain-induced metabolic dysfunction. TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170. FUNDING. This work was supported by NIH grants UL1 RR024992 (Clinical Translational Science Award), DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Center Grant), and UL1 TR000450 (KL2 Award); a Central Society for Clinical and Translational Research Early Career Development Award; and by grants from the Longer Life Foundation and the Kilo Foundation.

  17. Adverse effect of outdoor air pollution on cardiorespiratory fitness in Chinese children

    NASA Astrophysics Data System (ADS)

    Gao, Yang; Chan, Emily Y. Y.; Zhu, Yingjia; Wong, Tze Wai

    2013-01-01

    Little is known about the health impact of air pollution on children's cardiovascular health. A cross-sectional study was conducted and data was analysed in 2048 Chinese schoolchildren (aged 8-10 years) in three districts of Hong Kong to examine the association between exposure to outdoor air pollution and cardiorespiratory fitness. Annual means of ambient PM10, SO2, NO2 and O3 from 1996 to 2003 were used to estimate individual exposure of the subjects. Cardiorespiratory fitness was measured for maximal oxygen uptake (VO2max), predicted by the multistage fitness test (MFT). Height and weight were measured and other potential confounders were collected with questionnaires. Analysis of covariance was performed to estimate the impact of air pollution on complete speed in the MFT and predicted VO2max. The results showed that children in high-pollution district had significantly lower complete speed and predicted VO2max compared to those in low- and moderate-pollution districts. Complete speed and predicted VO2max was estimated to reduce 0.327 km h-1 and 1.53 ml kg-1 min-1 per 10 μg m-3 increase in PM10 annual mean respectively, with those in girls being greater than in boys. Being physically active could not significantly result in improved cardiorespiratory fitness in polluted districts. The adverse effect seems to be independent of short-term exposure to air pollution. We concluded that long-term exposure to higher outdoor air pollution levels was negatively associated with cardiorespiratory fitness in Chinese schoolchildren, especially for girls. PM10 is the most relevant pollutant of the adverse effect. Elevated cardiorespiratory fitness observed in physically activate children could be negated by increased amount of inhaled pollutants during exercise.

  18. Mitigating Adverse Effects of a Human Mission on Possible Martian Indigenous Ecosystems

    NASA Astrophysics Data System (ADS)

    Lupisella, M. L.

    2000-07-01

    Although human beings are, by most standards, the most capable agents to search for and detect extraterrestrial life, we are also potentially the most harmful. While there has been substantial work regarding forward contamination with respect to robotic missions, the issue of potential adverse effects on possible indigenous Martian ecosystems, such as biological contamination, due to a human mission has remained relatively unexplored and may require our attention now as this presentation will try to demonstrate by exploring some of the relevant scientific questions, mission planning challenges, and policy issues. An informal, high-level mission planning decision tree will be discussed and is included as the next page of this abstract. Some of the questions to be considered are: (1) To what extent could contamination due to a human presence compromise possible indigenous life forms? (2) To what extent can we control contamination? For example, will it be local or global? (3) What are the criteria for assessing the biological status of Mars, both regionally and globally? For example, can we adequately extrapolate from a few strategic missions such as sample return missions? (4) What should our policies be regarding our mission planning and possible interaction with what are likely to be microbial forms of extraterrestrial life? (5) Central to the science and mission planning issues is the role and applicability of terrestrial analogs, such as Lake Vostok for assessing drilling issues, and modeling techniques. Central to many of the policy aspects are scientific value, international law, public concern, and ethics. Exploring this overall issue responsibly requires an examination of all these aspects and how they interrelate. A chart is included, titled 'Mission Planning Decision Tree for Mitigating Adverse Effects to Possible Indigenous Martian Ecosystems due to a Human Mission'. It outlines what questions scientists should ask and answer before sending humans to Mars.

  19. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles.

    PubMed

    Krentz, A J; Fujioka, K; Hompesch, M

    2016-06-01

    Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs.

  20. Mitigating Adverse Effects of a Human Mission on Possible Martian Indigenous Ecosystems

    NASA Technical Reports Server (NTRS)

    Lupisella, M. L.

    2000-01-01

    Although human beings are, by most standards, the most capable agents to search for and detect extraterrestrial life, we are also potentially the most harmful. While there has been substantial work regarding forward contamination with respect to robotic missions, the issue of potential adverse effects on possible indigenous Martian ecosystems, such as biological contamination, due to a human mission has remained relatively unexplored and may require our attention now as this presentation will try to demonstrate by exploring some of the relevant scientific questions, mission planning challenges, and policy issues. An informal, high-level mission planning decision tree will be discussed and is included as the next page of this abstract. Some of the questions to be considered are: (1) To what extent could contamination due to a human presence compromise possible indigenous life forms? (2) To what extent can we control contamination? For example, will it be local or global? (3) What are the criteria for assessing the biological status of Mars, both regionally and globally? For example, can we adequately extrapolate from a few strategic missions such as sample return missions? (4) What should our policies be regarding our mission planning and possible interaction with what are likely to be microbial forms of extraterrestrial life? (5) Central to the science and mission planning issues is the role and applicability of terrestrial analogs, such as Lake Vostok for assessing drilling issues, and modeling techniques. Central to many of the policy aspects are scientific value, international law, public concern, and ethics. Exploring this overall issue responsibly requires an examination of all these aspects and how they interrelate. A chart is included, titled 'Mission Planning Decision Tree for Mitigating Adverse Effects to Possible Indigenous Martian Ecosystems due to a Human Mission'. It outlines what questions scientists should ask and answer before sending humans to Mars.

  1. The adverse health effects of oil spills: a review of the literature and a framework for medically evaluating exposed individuals.

    PubMed

    Levy, Barry S; Nassetta, William J

    2011-01-01

    In April 2010, an explosion on an oil rig in the Gulf of Mexico killed 11 workers, injured 17 workers, and spilled an estimated 185 million gallons of crude oil into the Gulf. Adverse effects on the health of cleanup workers, fishermen, and others as well as on the ecosystem are being studied. This paper reviews published studies of the adverse health effects due to previous oil spills. Acute effects have included: respiratory, eye, and skin symptoms; headache; nausea; dizziness; and tiredness or fatigue. Chronic effects have included: psychological disorders, respiratory disorders, genotoxic effects, and endocrine abnormalities. We also present a systematic approach to evaluating individuals exposed to oil spills.

  2. Estradiol uptake, toxicity, metabolism, and adverse effects on cadmium-treated amphibian embryos.

    PubMed Central

    Fridman, Osvaldo; Corró, Lucrecia; Herkovits, Jorge

    2004-01-01

    The exposure of Bufo arenarum embryos to 25 micromol/L 17beta-estradiol (E2) resulted in 100% lethality within 48 hr, whereas 10 micromol//L E2 was the no observed effect concentration value for short-term chronic (7 days) exposure. The toxicity profile curves show that lethal effects were proportional to the E2 concentration and the time of exposure. The E2 uptake resulted in 20.1 ng E2/mg embryo at 8 hr posttreatment, but 67.3% of this value was achieved during the first 30 min of incubation with this estrogen. Regarding metabolism, the embryos synthesize estrone (E1) from E2 by means of 17beta-hydroxysteroid dehydrogenase. Simultaneous treatments of Bufo arenarum embryos with 1 mg/L Cd2+ and 0.1, 1, or 10 micromol/L E2 enhanced the lethality exerted by cadmium in 76.7, 80, and 83.3% of embryos, respectively. The results indicate that estrogenic endocrine disruptors could have an adverse effect on amphibian embryos and enhance the toxic effect of Cd on amphibian embryos. This study points to the possibility of using the AMPHITOX test as a screening method for potential endocrine disruption as well as the combined effects of chemical mixtures. PMID:15175173

  3. Doping with anabolic androgenic steroids (AAS): Adverse effects on non-reproductive organs and functions.

    PubMed

    Nieschlag, Eberhard; Vorona, Elena

    2015-09-01

    Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17α-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms.

  4. DRD4-exonIII-VNTR moderates the effect of childhood adversities on emotional resilience in young-adults.

    PubMed

    Das, Debjani; Cherbuin, Nicolas; Tan, Xiaoyun; Anstey, Kaarin J; Easteal, Simon

    2011-01-01

    Most individuals successfully maintain psychological well-being even when exposed to trauma or adversity. Emotional resilience or the ability to thrive in the face of adversity is determined by complex interactions between genetic makeup, previous exposure to stress, personality, coping style, availability of social support, etc. Recent studies have demonstrated that childhood trauma diminishes resilience in adults and affects mental health. The Dopamine receptor D4 (DRD4) exon III variable number tandem repeat (VNTR) polymorphism was reported to moderate the impact of adverse childhood environment on behaviour, mood and other health-related outcomes. In this study we investigated whether DRD4-exIII-VNTR genotype moderates the effect of childhood adversities (CA) on resilience. In a representative population sample (n = 1148) aged 30-34 years, we observed an interactive effect of DRD4 genotype and CA (β = 0.132; p = 0.003) on resilience despite no main effect of the genotype when effects of age, gender and education were controlled for. The 7-repeat allele appears to protect against the adverse effect of CA since the decline in resilience associated with increased adversity was evident only in individuals without the 7-repeat allele. Resilience was also significantly associated with approach-/avoidance-related personality measures (behavioural inhibition/activation system; BIS/BAS) measures and an interactive effect of DRD4-exIII-VNTR genotype and CA on BAS was observed. Hence it is possible that approach-related personality traits could be mediating the effect of the DRD4 gene and childhood environment interaction on resilience such that when stressors are present, the 7-repeat allele influences the development of personality in a way that provides protection against adverse outcomes.

  5. [Changes of menstruation patterns and adverse effects during the treatment of LNG-IUS for symptomatic adenomyosis].

    PubMed

    Li, L; Leng, J H; Zhang, J J; Jia, S Z; Li, X Y; Shi, J H; Dai, Y; Zhang, J R; Li, T; Xu, X X; Liu, Z Z; You, S S; Chang, X Y; Lang, J H

    2016-09-25

    Objective: To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system(LNG-IUS)for symptomatic adenomyosis in a prospective cohort study. Methods: From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients' parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results: Totally 1 100 cases met inclusion criteria, with median age 36 years(range 20-44 years), median follow-up 35 months(range 1 -108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383)and 29.6%(82/277)patients achieved amenorrhea respectively(P<0.01). Total and subclassification of adverse effects decreased significantly(P<0.01). Within 12 months and >12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status(all P> 0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions: During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened

  6. Effect of renal function on prognosis in chronic heart failure.

    PubMed

    Löffler, Adrián Ignacio; Cappola, Thomas P; Fang, James; Hetzel, Scott J; Kadlec, Andrew; Astor, Brad; Sweitzer, Nancy K

    2015-01-01

    Renal dysfunction (RD) is associated with increased mortality in heart failure (HF). The aim of this study was to identify whether worsened or improved renal function during mid-term follow-up is associated with worsened outcomes in patients with chronic HF. A total of 892 participants from a multicenter cohort study of chronic HF were followed over 3.1 ± 1.9 years of enrollment. Worsened and improved renal functions were tested with multivariate models as independent predictors of HF hospitalization and mortality. Although 12% of subjects experienced a ≥25% decrease in estimated glomerular filtration rate (eGFR), 17% experienced a ≥25% increase in eGFR, and there was stability of kidney function observed in the cohort as a whole. The quartile with the worst RD at any point in time had increased risk of HF hospitalization and mortality. Worsened eGFR was associated with HF outcomes in the unadjusted (hazard ratio = 1.71, 95% confidence interval 1.04 to 2.81, p = 0.035), but not the adjusted analysis. Improvement in eGFR was not associated with outcome (p = 0.453). In chronic HF, the severity of RD predicts risk of poor outcome better than changes in renal function during mid-term follow-up. This suggests that in patients with appropriately treated chronic HF, worsening renal function in itself does not yield useful prognostic information and may not reflect poor outcome.

  7. Novel biopesticide based on a spider venom peptide shows no adverse effects on honeybees.

    PubMed

    Nakasu, Erich Y T; Williamson, Sally M; Edwards, Martin G; Fitches, Elaine C; Gatehouse, John A; Wright, Geraldine A; Gatehouse, Angharad M R

    2014-07-22

    Evidence is accumulating that commonly used pesticides are linked to decline of pollinator populations; adverse effects of three neonicotinoids on bees have led to bans on their use across the European Union. Developing insecticides that pose negligible risks to beneficial organisms such as honeybees is desirable and timely. One strategy is to use recombinant fusion proteins containing neuroactive peptides/proteins linked to a 'carrier' protein that confers oral toxicity. Hv1a/GNA (Galanthus nivalis agglutinin), containing an insect-specific spider venom calcium channel blocker (ω-hexatoxin-Hv1a) linked to snowdrop lectin (GNA) as a 'carrier', is an effective oral biopesticide towards various insect pests. Effects of Hv1a/GNA towards a non-target species, Apis mellifera, were assessed through a thorough early-tier risk assessment. Following feeding, honeybees internalized Hv1a/GNA, which reached the brain within 1 h after exposure. However, survival was only slightly affected by ingestion (LD50>100 µg bee(-1)) or injection of fusion protein. Bees fed acute (100 µg bee(-1)) or chronic (0.35 mg ml(-1)) doses of Hv1a/GNA and trained in an olfactory learning task had similar rates of learning and memory to no-pesticide controls. Larvae were unaffected, being able to degrade Hv1a/GNA. These tests suggest that Hv1a/GNA is unlikely to cause detrimental effects on honeybees, indicating that atracotoxins targeting calcium channels are potential alternatives to conventional pesticides.

  8. Mitigation of Adverse Effects Caused by Shock Wave Boundary Layer Interactions Through Optimal Wall Shaping

    NASA Technical Reports Server (NTRS)

    Liou, May-Fun; Lee, Byung Joon

    2013-01-01

    It is known that the adverse effects of shock wave boundary layer interactions in high speed inlets include reduced total pressure recovery and highly distorted flow at the aerodynamic interface plane (AIP). This paper presents a design method for flow control which creates perturbations in geometry. These perturbations are tailored to change the flow structures in order to minimize shock wave boundary layer interactions (SWBLI) inside supersonic inlets. Optimizing the shape of two dimensional micro-size bumps is shown to be a very effective flow control method for two-dimensional SWBLI. In investigating the three dimensional SWBLI, a square duct is employed as a baseline. To investigate the mechanism whereby the geometric elements of the baseline, i.e. the bottom wall, the sidewall and the corner, exert influence on the flow's aerodynamic characteristics, each element is studied and optimized separately. It is found that arrays of micro-size bumps on the bottom wall of the duct have little effect in improving total pressure recovery though they are useful in suppressing the incipient separation in three-dimensional problems. Shaping sidewall geometry is effective in re-distributing flow on the side wall and results in a less distorted flow at the exit. Subsequently, a near 50% reduction in distortion is achieved. A simple change in corner geometry resulted in a 2.4% improvement in total pressure recovery.

  9. Effects of a Psychosocial Couple-Based Prevention Program on Adverse Birth Outcomes

    PubMed Central

    Roettger, Michael E.; Jones, Damon E.; Paul, Ian M.; Kan, Marni L.

    2015-01-01

    Although maternal stress and depression have been linked to adverse birth outcomes (ABOs), few studies have investigated preventive interventions targeting maternal mental health as a means of reducing ABOs. This randomized controlled study examines the impact of Family Foundations (FF)—a transition to parenthood program for couples focused on promoting coparenting quality, with previously documented impact on maternal stress and depression—on ABOs. We also examine whether intervention buffers birth outcomes from the negative effect of elevated salivary cortisol levels. We use intent-to-treat analyses to assess the main effects of the FF intervention on ABOs (prematurity, birth weight, pregnancy complications, Cesarean section, and days in hospital for mothers and infants) among 148 expectant mothers. We also test the interaction of cortisol with intervention condition status in predicting ABOs. FF participation was associated with reduced risk of C-section (OR .357, p < 0.05, 95 % CI 0.149, 0.862), but did not have main effects on other ABOs. FF significantly buffered (p < 0.05) the negative impact of maternal cortisol on birth weight, gestational age, and days in hospital for infants; that is, among women with relatively higher levels of prenatal cortisol, the intervention reduced ABOs. These results demonstrate that a psycho-educational program for couples reduces incidence of ABOs among higher risk women. Future work should test whether reduced maternal stress and depression mediate these intervention effects. PMID:24969352

  10. IMPACT OF ABDOMINAL OBESITY ON INCIDENCE OF ADVERSE METABOLIC EFFECTS ASSOCIATED WITH ANTIHYPERTENSIVE MEDICATIONS

    PubMed Central

    Cooper-DeHoff, Rhonda M.; Wen, Sheron; Beitelshees, Amber L.; Zineh, Issam; Gums, John G.; Turner, Stephen T.; Gong, Yan; Hall, Karen; Parekh, Vishal; Chapman, Arlene B.; Boerwinkle, Eric; Johnson, Julie A.

    2009-01-01

    We assessed adverse metabolic effects (AMEs) of atenolol and hydrochlorothiazide (HCTZ) among hypertensive patients with and without abdominal obesity using data from a randomized, open-label study of hypertensive patients without evidence of cardiovascular disease or diabetes. Intervention included randomization to HCTZ 25mg or atenolol 100mg monotherapy followed by their combination. Fasting glucose, insulin, triglycerides, HDL cholesterol and uric acid were measured at baseline and after mono-and combination therapy. Outcomes included new occurrence of and predictors for new cases of glucose ≥ 100mg/dl (impaired fasting glucose [IFG]), triglyceride ≥ 150 mg/dl, HDL ≤ 40mg/dl for men or ≤ 50mg/dl for women, or new onset diabetes according to presence or absence of abdominal obesity. Abdominal obesity was present in 167/395 (58%). Regardless of strategy, in those with abdominal obesity, 20% had IFG at baseline compared with 40% at end of study (p<0.0001). Proportion with triglycerides ≥ 150 mg/dl increased from 33% at baseline to 46% at end of study (p<0.01). New onset diabetes occurred in 13 (6%) with and in 4 (2%) without abdominal obesity. Baseline levels of glucose, triglyceride and HDL predicted adverse outcomes and predictors for new onset diabetes after monotherapy in those with abdominal obesity included HCTZ strategy (OR 47, 95% CI 2.55-862), female sex (OR 31.3, 95% CI 2.10-500) and uric acid (OR 3.2, 95% CI 2.35-7.50). Development of AME, including new onset diabetes associated with short term exposure to HCTZ and atenolol was more common in those with abdominal obesity. PMID:19917874

  11. The adverse effect of phytoestrogens on the synthesis and secretion of ovarian oxytocin in cattle.

    PubMed

    Mlynarczuk, J; Wrobel, M H; Kotwica, J

    2011-02-01

    The current investigations were undertaken to study the mechanism of the adverse effect of phytoestrogens on the function of bovine granulosa (follicles >1< cm in diameter) and luteal cells from day 1-5, 6-10, 11-15, 16-19 of the oestrous cycle. The cells were incubated with genistein, daidzein or coumestrol (each at the dose of 1 × 10(-6) m). The viability and secretion of estradiol (E2), progesterone (P4) and oxytocin (OT) were measured after 72 h of incubation. Moreover, the expression of mRNA for neurophysin-I/OT (NP-I/OT; precursor of OT) and peptidyl-glycine-α-amidating monooxygenase (PGA, an enzyme responsible for post-translational OT synthesis) was determined after 8 h of treatment. None of the phytoestrogens used affected the viability of cells except for coumestrol. The increased secretion of E2 and P4 was only obtained by coumestrol (p<0.05) from granulosa cells from follicles <1cm in diameter and decreased from luteal cells on days 11-15 of the oestrous cycle, respectively. All three phytoestrogens stimulated (p<0.05) OT secretion from granulosa and luteal cells in all stages of the oestrous cycle and the expression of NP-I/OT mRNA in the both types of cells. The expression of mRNA for PGA was stimulated (p<0.05) by daidzein and coumestrol in granulosa cells, and by genistein and coumestrol in luteal cells. In conclusion, our results demonstrate that these phytoestrogens can impair the ovary function in cattle by adversely affecting the synthesis of OT in follicles and in corpus luteum. However, their influence on the ovarian steroids secretion was less evident.

  12. Visceral leishmaniasis in renal transplant recipients: successful treatment with liposomal amphotericin B (AmBisome).

    PubMed

    Boletis, J N; Pefanis, A; Stathakis, C; Helioti, H; Kostakis, A; Giamarellou, H

    1999-06-01

    Visceral leishmaniasis (VL) is a rare disease in renal transplant recipients. Liposomal amphotericin B (AmBisome) is known to be effective against VL. However, previously there has been no experience with administration of such treatment to renal transplant recipients. We report herein four patients with VL complicating renal transplantation who were treated successfully with liposomal amphotericin B (total dose, 23-40 mg/kg). Neither adverse reactions nor clinical relapses of VL were observed.

  13. The Development of Countermeasures for Space Radiation Induced Adverse Health Effects

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann

    The Development of Countermeasures for Space Radiation Induced Adverse Health Effects Ann R. Kennedy Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, United States 19104-6072 The development of countermeasures for radiation induced adverse health effects is a lengthy process, particularly when the countermeasure/drug has not yet been evaluated in human trials. One example of a drug developed from the bench to the clinic is the soybean-derived Bowman-Birk inhibitor (BBI), which has been developed as a countermeasure for radiation induced cancer. It was originally identified as a compound/drug that could prevent the radiation induced carcinogenic process in an in vitro assay system in 1975. The first observation that BBI could inhibit carcinogenesis in animals was in 1985. BBI received Investigational New Drug (IND) Status with the U.S. Food and Drug Administration (FDA) in 1992 (after several years of negotiation with the FDA about the potential IND status of the drug), and human trials began at that time. Phase I, II and III human trials utilizing BBI have been performed under several INDs with the FDA, and an ongoing Phase III trial will be ending in the very near future. Thus, the drug has been in development for 35 years at this point, and it is still not a prescription drug on the market which is available for human use. A somewhat less time-consuming process is to evaluate compounds that are on the GRAS (Generally Recognized as Safe) list. These compounds would include some over-the-counter medications, such as antioxidant vitamins utilized in human trials at the levels for which Recommended Dietary Allowances (RDAs) have been established. To determine whether GRAS substances are able to have beneficial effects on radiation induced adverse health effects, it is still likely to be a lengthy process involving many years to potentially decades of human trial work. The

  14. More effective assessment of adverse effects and comorbidities in epilepsy: results of a Phase II communication study.

    PubMed

    Stern, John M; Labiner, David M; Gilliam, Frank G; Penovich, Patricia E; Onofrey, Meaghan; Eagan, Corey A; Holmes, Gregory L

    2011-11-01

    Research was conducted to evaluate conversations about epilepsy between community-based neurologists and patients. Adverse effects of antiepileptic drugs and mood/behavioral issues were infrequently discussed, and neurologists and patients disagreed about these issues postvisit. Follow-up research was conducted to assess the impact of a previsit assessment tool on discussions of epilepsy. Twenty neurologists reviewed a tool incorporating questions from validated instruments (Adverse Events Profile [AEP] and Neurological Disorders Depression Inventory for Epilepsy [NDDI-E]). Naturally occurring interactions between neurologists and 60 patients were recorded. Neurologists and patients were interviewed separately. All components were transcribed and analyzed using sociolinguistics. Using the previsit assessment tool increased the number of discussions about adverse effects and mood/behavioral issues and increased neurologist-patient agreement about issues postvisit. Visit length did not increase significantly when the tool was used. Ten months after follow-up research, 50% of neurologists reported continuing to use the tool in everyday practice with patients with epilepsy.

  15. Biological sensitivity to context: the interactive effects of stress reactivity and family adversity on socioemotional behavior and school readiness.

    PubMed

    Obradović, Jelena; Bush, Nicole R; Stamperdahl, Juliet; Adler, Nancy E; Boyce, W Thomas

    2010-01-01

    This study examined the direct and interactive effects of stress reactivity and family adversity on socioemotional and cognitive development in three hundred and thirty-eight 5- to 6-year-old children. Neurobiological stress reactivity was measured as respiratory sinus arrhythmia and salivary cortisol responses to social, cognitive, sensory, and emotional challenges. Adaptation was assessed using child, parent, and teacher reports of externalizing symptoms, prosocial behaviors, school engagement, and academic competence. Results revealed significant interactions between reactivity and adversity. High stress reactivity was associated with more maladaptive outcomes in the context of high adversity but with better adaption in the context of low adversity. The findings corroborate a reconceptualization of stress reactivity as biological sensitivity to context by showing that high reactivity can both hinder and promote adaptive functioning.

  16. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment

    ERIC Educational Resources Information Center

    Kiff, Cara J.; Cortes, Rebecca C.; Lengua, Liliana J.; Kosterman, Rick; Hawkins, J. David; Mason, W. Alex

    2012-01-01

    Exposure to adversity during childhood and adolescence predicts adjustment across development. Furthermore, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal…

  17. Conversion from a calcineurin inhibitor-based immunosuppressive regimen to everolimus in renal transplant recipients: effect on renal function and proteinuria.

    PubMed

    Morales, J; Fierro, A; Benavente, D; Zehnder, C; Ferrario, M; Contreras, L; Herzog, C; Buckel, E

    2007-04-01

    New immunosuppressive agents are being actively researched to avoid complications of chronic allograft nephropathy (CAN), calcineurin inhibitor (CNI) nephrotoxicity, and posttransplantation cancer. The family of mTOR inhibitors offers a unique immunosuppressive opportunity to avoid CNI toxicity and reduce the incidence of malignancy. Nevertheless, increasing data have demonstrated that sirolimus (SRL), the first mTOR introduced in the treatment of solid organ transplant recipients, induces proteinuria, an adverse event that could produce deterioration of long-term renal function. In this short-term study of patients followed for 1 to 16 months, we examined changes in renal function and proteinuria among renal transplant recipients converted from a CNI-based regimen to an everolimus (EVL)-based one, a recently introduced mTOR inhibitor. Our data showed that renal function can be optimized after conversion to EVL by up to 42% in recipients showing CAN grade 1 or 2, or CNI nephrotoxicity. Importantly, patients who improved their creatinine clearance did not show increased proteinuria measured in a voided specimen as the ratio of urinary protein and creatinine concentration (P/C). These results, if confirmed with long-term follow-up and a larger number of patients, would allow us to consider EVL as a promising agent for maintenance immunosuppressive regimens in kidney transplantation.

  18. Renal interstitial sclerosis in aging: effects of enalapril and nifedipine.

    PubMed

    Inserra, F; Romano, L A; de Cavanagh, E M; Ercole, L; Ferder, L F; Gomez, R A

    1996-05-01

    The effects of nifedipine and enalapril on age-associated renal interstitial fibrosis were investigated in 60 CF1 female mice. Mice received 20 mg enalapril (ENAL) per L (N = 20), or 40 mg nifedipine (NIF) per L (N = 20) in their drinking water. Control (CONT) mice received tap water ad libitum. The percentages of both interstitial peritubular sclerosis (IPS) in cortex and interstitial medullary sclerosis (IMS) were determined. Kidney tissue was studied using immunological techniques and optical (OM) and electron microscopy (EM) to analyze the expression of renin. alpha-SM-actin and vimentine expression were also evaluated. The results showed that blood pressure levels in ENAL or NIF animals were not different from those of CONT. Renin expression was observed in arcuate vessels (AV) in ENAL animals, whereas no renin staining in AV was found in either NIF or CONT animals. Renin immunoreactivity in the juxtaglomerular apparatus was more intense in ENAL mice, as compared with NIF or CONT animals. Laboratory testing showed the following values: proteinuria (mg/mL): CONT 6.1 +/- 0.6, NIF 11.2 +/- 2.3, and ENAL 1.0 +/- 0.6 (P < 0.05); creatinine: CONT 1.37 +/- 0.24, NIF 0.87 +/- 0.16, and ENAL 0.63 +/- 0.1 (P < 0.01). The percentages of interstitial sclerosis were: %IPS: CONT 18.12 +/- 1.1, NIF 17.40 +/- 0.9, and ENAL 3.42 +/- 1.3 (P < 0.01); %IMS: CONT 23.41 +/- 1.5, NIF 21.80 +/- 1.9, and ENAL 6.12 +/- 1.2 (P < 0.01). Percentages of alpha-SM-actin expression were: CONT 13.10 +/- 1.9, NIF 13.80 +/- 0.2, and ENAL 1.00 +/- 0.1 (P < 0.01). Vimentine staining showed no differences among the groups. It was concluded that enalapril reduces the peritubular and medullar interstitial fibrosis, whereas nifedipine has no effect.

  19. Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

    PubMed

    Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U

    2016-09-21

    Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple (18)F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar

  20. Adverse effect of agroecosystem pond water on biological endpoints of common toad (Rhinella arenarum) tadpoles.

    PubMed

    Babini, María Selene; Bionda, Clarisa de Lourdes; Salas, Nancy Edith; Martino, Adolfo Ludovico

    2016-08-01