Terbinafine induced pityriasis rosea-like eruption.

PubMed

George, Anisha; Bhatia, Anuradha; Kanish, Bimal; Williams, Abhilasha

2015-01-01

Terbinafine is an allylamine antifungal agent which is widely used for the treatment of fungal infections. Cutaneous side effects have been reported in 2% of the patients on terbinafine therapy with many morphological patterns. We report a case of terbinafine induced pityriasis rosea, a very rare side effect of terbinafine. This report emphasizes the importance of counseling the patient to report immediately in the event of a cutaneous eruption.

A Cutaneous Lupus Erythematosus-Like Eruption Induced by Hydroxyurea.

PubMed

Yanes, Daniel A; Mosser-Goldfarb, Joy L

2017-01-01

Hydroxyurea is a medication with many well-described cutaneous side effects, notably the dermatomyositis-like eruption known as hydroxyurea dermopathy. Although systemic lupus erythematosus has been reported with hydroxyurea use, cutaneous lupus has not. We report a novel case of chronic cutaneous lupus induced by hydroxyurea and propose that this is a side effect that is distinct from hydroxyurea dermopathy. © 2016 Wiley Periodicals, Inc.

Aged garlic extract protects against methotrexate-induced apoptotic cell injury of IEC-6 cells.

PubMed

Horie, Toshiharu; Li, Tiesong; Ito, Kousei; Sumi, Shin-ichiro; Fuwa, Toru

2006-03-01

Gastrointestinal toxicity is one of the most serious side effects of methotrexate (MTX) treatment. The side effects often disrupt the cancer chemotherapy. We previously reported that aged garlic extract (AGE) protects the small intestine of rats from MTX-induced damage. In this study, the protection of AGE against MTX-induced damage of IEC-6 cells originating from the rat jejunum crypt was investigated. MTX decreased the viability of IEC-6 cells, but this effect was prevented by AGE (0.5%). The MTX-induced apoptosis of IEC-6 cells was depressed by AGE. These results indicated that AGE protects IEC-6 cells from the MTX-induced damage. AGE may be useful in cancer chemotherapy with MTX because it reduces MTX-induced intestinal damage.

The PsyLOG mobile application: development of a tool for the assessment and monitoring of side effects of psychotropic medication.

PubMed

Kuzman, Martina Rojnic; Andlauer, Olivier; Burmeister, Kai; Dvoracek, Boris; Lencer, Rebekka; Koelkebeck, Katja; Nawka, Alexander; Riese, Florian

2017-06-01

Mobile health interventions are regarded as affordable and accessible tools that can enhance standard psychiatric care. As part of the mHealth Psycho-Educational Intervention Versus Antipsychotic-Induced Side Effects (mPIVAS) project (www.psylog.eu), we developed the mobile application "PsyLOG" based on mobile "smartphone" technology to monitor antipsychotic-induced side effects. The aim of this paper is to describe the rationale and development of the PsyLOG and its clinical use. The PsyLOG application runs on smartphones with Android operating system. The application is currently available in seven languages (Croatian, Czech, English, French, German, Japanese and Serbian). It consists of several categories: "My Drug Effects", "My Life Styles", "My Charts", "My Medication", "My Strategies", "My Supporters", "Settings" and "About". The main category "My Drug Effects" includes a list of 30 side effects with the possibility to add three additional side effects. Side effects are each accompanied by an appropriate description and the possibility to rate its severity on a visual analogue scale from 0-100%. The PsyLOG application is intended to enhance the link between patients and mental health professionals, serving as a tool that more objectively monitors side-effects over certain periods of time. To the best of our knowledge, no such applications have so far been developed for patients taking antipsychotic medication or for their therapists.

Synthetic Studies of Neoclerodane Diterpenes from Salvia divinorum: Identification of a Potent and Centrally Acting μ Opioid Analgesic with Reduced Abuse Liability.

PubMed

Crowley, Rachel Saylor; Riley, Andrew P; Sherwood, Alexander M; Groer, Chad E; Shivaperumal, Nirajmohan; Biscaia, Miguel; Paton, Kelly; Schneider, Sebastian; Provasi, Davide; Kivell, Bronwyn M; Filizola, Marta; Prisinzano, Thomas E

2016-12-22

Opioids are widely used to treat millions suffering from pain, but their analgesic utility is limited due to associated side effects. Herein we report the development and evaluation of a chemical probe exhibiting analgesia and reduced opioid-induced side effects. This compound, kurkinorin (5), is a potent and selective μ-opioid receptor (MOR) agonist (EC 50 = 1.2 nM, >8000 μ/κ selectivity). 5 is a biased activator of MOR-induced G-protein signaling over β-arrestin-2 recruitment. Metadynamics simulations of 5's binding to a MOR crystal structure suggest energetically preferred binding modes that differ from crystallographic ligands. In vivo studies with 5 demonstrate centrally mediated antinociception, significantly reduced rewarding effects, tolerance, and sedation. We propose that this novel MOR agonist may represent a valuable tool in distinguishing the pathways involved in MOR-induced analgesia from its side effects.

Tachykinin NK-1 and NK-3 selective agonists induce analgesia in the formalin test for tonic pain following intra-VTA or intra-accumbens microinfusions.

PubMed

Altier, N; Stewart, J

1997-12-01

Experiments were designed to examine the analgesic effects induced by selective tachykinin receptor agonists microinfused into either the ventral tegmental area (VTA) or nucleus accumbens septi (NAS). Rats were tested in the formalin test for tonic pain following an injection of 0.05 ml of 2.5% formalin into one hind paw immediately after bilateral intra-VTA infusions of either the NK-1 agonist, GR-73632 (0.005, 0.05 or 0.5 nmol/side), the NK-3 agonist, senktide (0.005, 0.5 or 1.5 nmol/side), or saline. Two weeks later, the saline-treated rats were assessed in the tail-flick test for phasic pain after infusions of the tachykinin agonists. Tail-flick latencies were recorded following immersion of the tail in 55 degrees C hot water at 10 min intervals for 1 h immediately after intra-VTA infusions of either GR-73632 (0.5 nmol/side), senktide (1.5 nmol/side) or saline. In a second group of rats, the same effects were studied after infusions into the nucleus accumbens (NAS) of GR-73632 (0.005, 0.5 or 1.5 nmol/side), senktide (0.005, 0.5 or 1.5 nmol/side), or saline. In both the VTA and NAS, the NK-1 and the NK-3 agonists caused significant analgesia in the formalin test, although the NK-1 agonist appeared to be more effective. Naltrexone (2.0 mg/kg) pretreatment failed to reverse the analgesic effects in the formalin test induced by intra-VTA infusions of the substance P (SP) analog, DiMe-C7 (3.0 microg/side), GR-73632 (0.5 nmol/side), or senktide (1.5 nmol/side). Neither compound given at either site was effective in the tail-flick test. These findings suggest that SP-dopamine (DA) interactions within the mesolimbic DA system play an important role in the inhibition of tonic pain. Furthermore, they support our earlier ideas that activation of midbrain DA systems by SP might play a role in stress- and/or pain-induced analgesia.

Severe valproate induced hyperammonemic encephalopathy successfully managed with peritoneal dialysis.

PubMed

Kumar, Amandeep; Suri, Ashish; Sharma, Bhawani S

2014-07-01

Valproic acid (VPA) is a commonly used drug for epilepsy, psychiatric disorders and migraine and is frequently used in neurosurgical intensive care units. Though most of its side-effects are mild and transient, certain idiosyncratic side-effects have been attributed to VPA. Valproate induced hyperammonemia (VIH) is one such side-effect. VIH can produce symptoms of encephalopathy known as valproate induced hyperammonemic encephalopathy (VHE). VIH and VHE usually respond to withdrawal of VPA. However, in some cases VHE can be unresponsive to supportive measures and severe enough to be life-threatening. In such cases, dialysis can be used to rapidly reverse hyperammonemia and VHE and can prove to be a lifesaving measure. We report such a case of VIH and life-threatening VHE in a postoperative neurosurgical patient that was managed successfully with peritoneal dialysis.

Terbinafine induced pityriasis rosea-like eruption

PubMed Central

George, Anisha; Bhatia, Anuradha; Kanish, Bimal; Williams, Abhilasha

2015-01-01

Terbinafine is an allylamine antifungal agent which is widely used for the treatment of fungal infections. Cutaneous side effects have been reported in 2% of the patients on terbinafine therapy with many morphological patterns. We report a case of terbinafine induced pityriasis rosea, a very rare side effect of terbinafine. This report emphasizes the importance of counseling the patient to report immediately in the event of a cutaneous eruption. PMID:26729964

Ayurveda for chemo-radiotherapy induced side effects in cancer patients.

PubMed

Metri, Kashinath; Bhargav, Hemant; Chowdhury, Praerna; Koka, Prasad S

2013-01-01

Chemotherapy drugs and radiotherapy are highly toxic and both damage adjacent healthy cells. Side effects may be acute (occurring within few weeks after therapy), intermediate or late (occurring months or years after the therapy). Some important side effects of chemotherapy are: nausea, vomiting, diarrhea, mucositis, alopecia, constipation etc; whereas radiation therapy though administered locally, can produce systemic side effects such as fatigue, anorexia, nausea, vomiting, alteration in the taste, sleep disturbance, headache, anemia, dry skin, constipation etc. Late complications of these therapies also include pharyngitis, esophagitis, laryngitis, persistent dysphagia, fatigue, hepatotoxicity, infertility and cognitive deficits. These arrays of side effects have a devastating effect on the quality of life of cancer survivors. Due to the inadequacy of most of the radio-protectors and chemo-protectors in controlling the side effects of conventional cancer therapy the complementary and alternative medicines have attracted the view of researchers and medical practitioners more recently. This review aims at providing a comprehensive management protocol of above mentioned chemo-radiotherapy induced side effects based on Ayurveda, which is an ancient system of traditional medicine practiced in Indian peninsula since 5000 BC. When the major side effects of chemo-radiotherapy are looked through an ayurvedic perspective, it appears that they are the manifestations of aggravated pitta dosha, especially under the group of disorders called Raktapitta (haemorrhage) or Raktadushti (vascular inflammation). Based on comprehensive review of ancient vedic literature and modern scientific evidences, ayurveda based interventions are put forth. This manuscript should help clinicians and people suffering from cancer to combat serious chemo-radiotherapy related side effects through simple but effective home-based ayurveda remedies. The remedies described are commonly available and safe. These simple ayurveda based solutions may act as an important adjuvant to chemo-radiotherapy and enhance the quality of life of cancer patients.

Balancing opioid-induced gastrointestinal side effects with pain management: Insights from the online community.

PubMed

Whitman, Cynthia B; Reid, Mark W; Arnold, Corey; Patel, Haridarshan; Ursos, Lyann; Sa'adon, Roee; Pourmorady, Jonathan; Spiegel, Brennan M R

2015-01-01

Opioids cause gastrointestinal (GI) symptoms such as nausea, vomiting, pain, and (in 40 percent) constipation that diminish patients' quality of life. Outside traditional surveys, little is known about the opioid-induced constipation (OIC) patient experience and its impact on pain management. The purpose of this study was to use data from social media platforms to qualitatively examine patient beliefs about OIC and other prominent GI side effects, their impact on effective pain management and doctor-patient interaction. The authors collected Tweets from March 25 to July 31, 2014, and e-forum posts from health-related social networking sites regardless of timestamp. The authors identified specific keywords related to opioids and GI side effects to locate relevant content in the dataset, which was then manually coded using ATLAS.ti software. The authors examined 2,519,868 Tweets and more than 1.8 billion e-forum posts, of which, 88,586 Tweets and 9,767 posts satisfied the search criteria. Three thousand three individuals experienced opioidinduced GI side effects, mostly related to phenanthrenes (n = 1,589), and 1,274 (42.4 percent) individuals described constipation. Over-the-counter medications and nonevidence-based natural approaches were most commonly used to alleviate constipation. Many individuals questioned, rotated, reduced, or stopped their opioid treatments as a result of their GI side effects. Investigation of social media reveals a struggle to balance pain management with opioid-induced GI side effects, especially constipation. Individuals are often unprepared to treat OIC, to modify opioid regiments without medical advice, and to resort to using natural remedies and treatments lacking scientific evidence of effectiveness. These results identify opportunities to improve physician-patient communication and explore effective treatment alternatives.

Is side-viewing endoscope assisted balloon dilatation better for corrosive gastric outlet obstruction?

PubMed

Katiyar, Prashant; Nijhawan, Sandeep; Saradava, Vimal; Nagaich, Neeraj; Gupta, Gaurav; Mathur, Amit; Nepalia, Subhash

2013-11-01

Endoscopic balloon dilatation (EBD) is an effective therapy for caustic-induced gastric outlet obstruction (GOO). Gaining access to the stricture site is the most important step. It is sometimes difficult to negotiate a balloon through the stricture with a front-viewing endoscope due to deformed anatomy of stomach. To overcome this technical difficulty, a side-viewing endoscope can be used. There is limited data regarding the use of side-viewing endoscopes in EBD. We here report on the short-term efficacy and safety of EBD in caustic-induced GOO. In technically difficult cases, a side-viewing endoscope was used for EBD and its efficacy and safety were assessed. The study included 25 patients with caustic-induced GOO. Patients underwent EBD using a through-the-scope balloon. Initial balloon dilatation was performed with a front-viewing endoscope. A side-viewing endoscope was used where negotiation across the stricture failed with a front-viewing endoscope. Dilatation was started at 8 mm diameter and was performed at 1-week intervals. The end point of dilatation was 15 mm diameter. In 18 patients successful balloon dilatation was possible with a front-viewing endoscope. A side-viewing endoscope was used in six patients as negotiation across the stricture was not possible with a front-viewing endoscope. In all six patients negotiation across the stricture followed by successful dilatation was successful with a side-viewing endoscope. Of the 25 patients included in this study, 24 (96%) achieved procedural success (18 with a front-viewing endoscope and 6 with a side-viewing endoscope) in 3-9 sessions. Our results show that EBD is a safe and effective option for caustic-induced GOO and in difficult cases a side-viewing endoscope can be used to achieve technical success.

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections

PubMed Central

Alhadeff, Amber L.; Holland, Ruby A.; Nelson, Alexandra; Grill, Harvey J.

2015-01-01

Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. SIGNIFICANCE STATEMENT To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of thousands of patients undergo chemotherapies each year, the neural mechanisms mediating their side effects are unknown. The current data outline a neural circuit activated by cisplatin chemotherapy and demonstrate that glutamate signaling in the amygdala, arising from hindbrain projections, is required for the full expression of cisplatin-induced malaise, anorexia, and body weight loss. Together, these data help to characterize the neural circuits and neurotransmitters mediating chemotherapy-induced energy balance dysregulation, which will ultimately provide an opportunity for the development of well tolerated cancer and anti-emetic treatments. PMID:26245970

Pharmacological Issues for Astronauts

NASA Technical Reports Server (NTRS)

Wotring, Virginia E.

2010-01-01

Medication-induced side effects, called untoward effects by pharmacologists, can be a problem with any medication. Few therapies are perfectly specific for the desired physiological activity; rather they act on multiple biological targets and result in multiple physiological effects. There are several strategies that are employed to prevent, alleviate or counteract medication-induced side effects. The administered dose may be optimized to the lowest possible amount that provides the desired therapeutic effect, with the expectation that untoward effects will be minimized by a lower dose. Empirical trials of different therapies for a particular medical problem may be used in the hopes of finding a drug with minimal side effects for a particular patient, or at least of finding a set of side effects that the patient considers tolerable. If these two strategies have been exhausted, it may be possible to administer another medication to block or ameliorate side effects. A recent search of published scientific literature has revealed that there are medications used in spaceflight that seem to be associated with a significant number of reports of untoward effects. To prevent future medical problems and to improve the well-being and productivity of crew members, it would be best to eliminate (or at least reduce) untoward effects. Reports from the literature will be examined, with the aim of identifying a strategy for reducing untoward effects.

Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice.

PubMed

Montalvo-Ortiz, Janitza L; Fisher, Daniel W; Rodríguez, Guadalupe; Fang, Deyu; Csernansky, John G; Dong, Hongxin

2017-08-01

Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects. In addition, we pretreated separate groups of young and aged mice with histone deacetylase (HDAC) inhibitors valproic acid (VPA) or entinostat (MS-275) and then administered HAL. Our results show that the motor side effects of HAL are exaggerated in aged mice as compared to young mice and that HDAC inhibitors are able to reverse the severity of these deficits. HAL-induced motor deficits in aged mice are associated with an age- and drug-dependent decrease in striatal D2R protein levels and functionality. Further, histone acetylation was reduced while histone tri-methylation was increased at specific lysine residues of H3 and H4 within the Drd2 promoter in the striatum of aged mice. HDAC inhibitors, particularly VPA, restored striatal D2R protein levels and functionality and reversed age- and drug-related histone modifications at the Drd2 promoter. These results suggest that epigenetic changes at the striatal Drd2 promoter drive age-related increases in antipsychotic side effect susceptibility, and HDAC inhibitors may be an effective adjunct treatment strategy to reduce side effects in aged populations.

Induced interaction in a Fermi gas with a BEC-BCS crossover

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu Zengqiang; Huang Kun; Yin Lan

2009-05-15

We study the effect of the induced interaction on the superfluid transition temperature of a Fermi gas with a Bose-Einstein condensation-Bardeen-Cooper-Schrieffer (BEC-BCS) crossover. The Gorkov-Melik-Barkhudarov theory about the induced interaction is extended from the BCS side to the entire crossover and the pairing fluctuation is treated in the approach by Nozieres and Schmitt-Rink. At unitarity, the induced interaction reduces the transition temperature by about 20%. In the BCS limit, the transition temperature is reduced by a factor of about 2.22, as found by Gorkov and Melik-Barkhudarov. Our result shows that the effect of the induced interaction is important both onmore » the BCS side and in the unitary region.« less

Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy.

PubMed

Hofmann, Lars; Forschner, Andrea; Loquai, Carmen; Goldinger, Simone M; Zimmer, Lisa; Ugurel, Selma; Schmidgen, Maria I; Gutzmer, Ralf; Utikal, Jochen S; Göppner, Daniela; Hassel, Jessica C; Meier, Friedegund; Tietze, Julia K; Thomas, Ioannis; Weishaupt, Carsten; Leverkus, Martin; Wahl, Renate; Dietrich, Ursula; Garbe, Claus; Kirchberger, Michael C; Eigentler, Thomas; Berking, Carola; Gesierich, Anja; Krackhardt, Angela M; Schadendorf, Dirk; Schuler, Gerold; Dummer, Reinhard; Heinzerling, Lucie M

2016-06-01

Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma as well as for other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential. In total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis. Anti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Autism and Obesity: Co-Occurring Conditions or Drug Side Effects

DTIC Science & Technology

2015-10-01

Antipsychotic-Induced Weight Gain ASD: Autism Spectrum Disorder BMI: Body Mass Index SSC: Simons Simplex Collection SNP: Single Nucleotide Polymorphism...AWARD NUMBER: W81XWH-14-1-0374 TITLE: Autism and Obesity: Co-Occurring Conditions or Drug Side Effects? PRINCIPAL INVESTIGATOR: Zohreh...SUBTITLE Autism and Obesity: Co-Occurring Conditions or Drug Side Effects? 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0374 5c. PROGRAM ELEMENT

Mean size estimation yields left-side bias: Role of attention on perceptual averaging.

PubMed

Li, Kuei-An; Yeh, Su-Ling

2017-11-01

The human visual system can estimate mean size of a set of items effectively; however, little is known about whether information on each visual field contributes equally to the mean size estimation. In this study, we examined whether a left-side bias (LSB)-perceptual judgment tends to depend more heavily on left visual field's inputs-affects mean size estimation. Participants were instructed to estimate the mean size of 16 spots. In half of the trials, the mean size of the spots on the left side was larger than that on the right side (the left-larger condition) and vice versa (the right-larger condition). Our results illustrated an LSB: A larger estimated mean size was found in the left-larger condition than in the right-larger condition (Experiment 1), and the LSB vanished when participants' attention was effectively cued to the right side (Experiment 2b). Furthermore, the magnitude of LSB increased with stimulus-onset asynchrony (SOA), when spots on the left side were presented earlier than the right side. In contrast, the LSB vanished and then induced a reversed effect with SOA when spots on the right side were presented earlier (Experiment 3). This study offers the first piece of evidence suggesting that LSB does have a significant influence on mean size estimation of a group of items, which is induced by a leftward attentional bias that enhances the prior entry effect on the left side.

Neuroprotective Effects of Drug-Induced Therapeutic Hypothermia in Central Nervous System Diseases.

PubMed

Ma, Junwei; Wang, Yibin; Wang, Zhong; Li, Haiying; Wang, Zhimin; Chen, Gang

2017-01-01

This review article focuses on the neuroprotective effect of drug-induced hypothermia in cerebrovascular diseases and discusses its related side effects. A systematic literature search was performed using Pubmed and Embase electronic databases for a retrospective analysis. Experimental studies have shown that drug-induced hypothermia alleviates brain damage and plays a neuroprotective role, thereby reducing mortality and ameliorating neurological deficits. Therefore, drug-induced hypothermia has an important research value and is worth further consideration in the clinical setting. However, drug-induced hypothermia is also associated with side effects, such as ventricular tachycardia, ventricular fibrillation, suppressed immune function, infection, electrolyte imbalance, glucose metabolism disorders, and skeletal muscle tremor. Existing drugs with cooling effects belong to the following categories: (1) dopamine receptor agonists; (2) cannabis; (3) opioid receptors; (4) vanilloid receptors; (5) vasopressins (potent neurotensin receptor agonists); (6) thyroid drugs; (7) adenosine drugs; and (8) purine drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections.

PubMed

Alhadeff, Amber L; Holland, Ruby A; Nelson, Alexandra; Grill, Harvey J; De Jonghe, Bart C

2015-08-05

Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of thousands of patients undergo chemotherapies each year, the neural mechanisms mediating their side effects are unknown. The current data outline a neural circuit activated by cisplatin chemotherapy and demonstrate that glutamate signaling in the amygdala, arising from hindbrain projections, is required for the full expression of cisplatin-induced malaise, anorexia, and body weight loss. Together, these data help to characterize the neural circuits and neurotransmitters mediating chemotherapy-induced energy balance dysregulation, which will ultimately provide an opportunity for the development of well tolerated cancer and anti-emetic treatments. Copyright © 2015 the authors 0270-6474/15/3511094-11$15.00/0.

Laxatives Do Not Improve Symptoms of Opioid-Induced Constipation: Results of a Patient Survey

PubMed Central

Emmanuel, Anton; Johnson, Martin; McSkimming, Paula; Dickerson, Sara

2017-01-01

Abstract Introduction Laxatives are commonly used to treat opioid-induced constipation, the commonest and most bothersome complication of opioids. However, laxatives have a nonspecific action and do not target underlying mechanisms of opioid-induced constipation; their use is associated with abdominal symptoms that negatively impact quality of life. Objective To assess the effects of laxatives in patients taking opioids for chronic pain. Methods One hundred ninety-eight UK patients who had taken opioid analgesics for at least one month completed a cross-sectional online or telephone survey. Questions addressed their pain condition, medication, and laxative use (including efficacy and side effects). The survey also assessed bowel function using the Bowel Function Index. Results Since starting their current opioid, 134 of 184 patients (73%) had used laxatives at some point and 122 (91%) of these were currently taking them. The most common laxatives were osmotics and stimulants. Laxative side effects were reported in 75%, most commonly gas, bloating/fullness, and a sudden urge to defecate. Side effects were more common in patients less than 40 years of age. Approximately half of patients said laxatives interfered with work and social activities, and one-fifth needed an overnight hospital stay because of their pain condition and/or constipation. Laxatives did not improve the symptoms of constipation, as assessed by the Bowel Function Index. Constipation was not related to opioid strength, dose of opioid, or number of laxatives taken. Conclusions Use of laxatives to treat opioid-induced constipation is often ineffective and associated with side effects. Instead of relieving the burden of opioid-induced constipation, laxative use is associated with a negative impact. PMID:28339544

Side effect profile similarities shared between antidepressants and immune-modulators reveal potential novel targets for treating major depressive disorders.

PubMed

Sun, Yu; Narayan, Vaibhav A; Wittenberg, Gayle M

2016-10-21

Side effects, or the adverse effects of drugs, contain important clinical phenotypic information that may be useful in predicting novel or unknown targets of a drug. It has been suggested that drugs with similar side-effect profiles may share common targets. The diagnostic class, Major Depressive Disorder, is increasingly viewed as being comprised of multiple depression subtypes with different biological root causes. One 'type' of depression generating substantial interest today focuses on patients with high levels of inflammatory burden, indicated by elevated levels of C-reactive proteins (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). It has been suggested that drugs targeting the immune system may have beneficial effect on this subtype of depressed patients, and several studies are underway to test this hypothesis directly. However, patients have been treated with both anti-inflammatory and antidepressant compounds for decades. It may be possible to exploit similarities in clinical readouts to better understand the antidepressant effects of immune-related drugs. Here we explore the space of approved drugs by comparing the drug side effect profiles of known antidepressants and drugs targeting the immune system, and further examine the findings by comparing the human cell line expression profiles induced by them with those induced by antidepressants. We found 7 immune-modulators and 14 anti-inflammatory drugs sharing significant side effect profile similarities with antidepressants. Five of the 7 immune modulators share most similar side effect profiles with antidepressants that modulate dopamine release and/or uptake. In addition, the immunosuppressant rapamycin and the glucocorticoid alclometasone induces transcriptional changes similar to multiple antidepressants. These findings suggest that some antidepressants and some immune-related drugs may affect common molecular pathways. Our findings support the idea that certain medications aimed at the immune system may be helpful in relieving depressive symptoms, and suggest that it may be of value to test immune-modulators for antidepressant-like activity in future proof-of-concept studies.

Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review.

PubMed

Ruston, Teresa; Hunter, Kathleen; Cummings, Greta; Lazarescu, Adriana

2013-01-01

Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality. To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults. A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria. Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.

[Side Effects of Smoking Cessation].

PubMed

Braun, Raffael; Huwiler, Bernhard

2018-06-01

Side Effects of Smoking Cessation Abstract. We present the case of a clozapine intoxication associated with aspiration pneumonia due to smoking cessation. Clozapine is mainly metabolized by CYP1A2. CYP1A2 is induced by cigarette smoking, which may change the plasma level of clozapine, especially if consuming habits change.

Stimulation of D2 receptors in the prefrontal cortex reduces PCP-induced hyperactivity, acetylcholine release and dopamine metabolism in the nucleus accumbens.

PubMed

Del Arco, A; Mora, F; Mohammed, A H; Fuxe, K

2007-02-01

The aim of the present study was to investigate the effects of stimulation of D2 receptors in the prefrontal cortex (PFC) on spontaneous motor activity and the hyperactivity induced by the psychomimetic phencyclidine (PCP). In addition, the effects of prefrontal D2 stimulation under PCP treatment on dialysate concentrations of acetylcholine, choline, dopamine, DOPAC and HVA in the nucleus accumbens were also investigated. Sprague-Dawley male rats were implanted with guide cannulae to perform bilateral injections into the medial PFC of the D2 agonist quinpirole (1.5 and 5 microg/side). Horizontal and vertical spontaneous motor activity and the motor activity induced by systemic injections of the PCP (5 mg/kg i.p.) were monitored in the open field. PFC injections of quinpirole (1.5 and 5 microg/side) significantly decreased horizontal and vertical spontaneous motor activity in a dose-related manner. These effects were blocked by the D2 antagonist raclopride (5 microg/side). Microinjections of quinpirole (1.5 and 5 microg/side) into the PFC also significantly attenuated the hyperactivity produced by PCP (5 mg/kg i.p.). PCP also increased dialysate concentrations of acetylcholine, and dopamine metabolites in the nucleus accumbens. These increases were also reduced by injections of quinpirole (5 microg/side) into the PFC. These results suggest that the stimulation of prefrontal D2 receptors plays an inhibitory role in regulating spontaneous and PCP-induced motor activity and also in the neurochemical changes produced by PCP in the nucleus accumbens.

A unified frame of predicting side effects of drugs by using linear neighborhood similarity.

PubMed

Zhang, Wen; Yue, Xiang; Liu, Feng; Chen, Yanlin; Tu, Shikui; Zhang, Xining

2017-12-14

Drug side effects are one of main concerns in the drug discovery, which gains wide attentions. Investigating drug side effects is of great importance, and the computational prediction can help to guide wet experiments. As far as we known, a great number of computational methods have been proposed for the side effect predictions. The assumption that similar drugs may induce same side effects is usually employed for modeling, and how to calculate the drug-drug similarity is critical in the side effect predictions. In this paper, we present a novel measure of drug-drug similarity named "linear neighborhood similarity", which is calculated in a drug feature space by exploring linear neighborhood relationship. Then, we transfer the similarity from the feature space into the side effect space, and predict drug side effects by propagating known side effect information through a similarity-based graph. Under a unified frame based on the linear neighborhood similarity, we propose method "LNSM" and its extension "LNSM-SMI" to predict side effects of new drugs, and propose the method "LNSM-MSE" to predict unobserved side effect of approved drugs. We evaluate the performances of LNSM and LNSM-SMI in predicting side effects of new drugs, and evaluate the performances of LNSM-MSE in predicting missing side effects of approved drugs. The results demonstrate that the linear neighborhood similarity can improve the performances of side effect prediction, and the linear neighborhood similarity-based methods can outperform existing side effect prediction methods. More importantly, the proposed methods can predict side effects of new drugs as well as unobserved side effects of approved drugs under a unified frame.

Effect of nitric oxide synthase inhibitor on increase in nasal mucosal blood flow induced by sensory and parasympathetic nerve stimulation in rats.

PubMed

Ogawa, Fumio; Hanamitsu, Masakazu; Ayajiki, Kazuhide; Aimi, Yoshinari; Okamura, Tomio; Shimizu, Takeshi

2010-06-01

Neural control of nasal blood flow (NBF) has not been systematically investigated. The aim of the present study was to evaluate the effect of electrical stimulation of both sensory and parasympathetic nerves innervating the nasal mucosal arteries on NBF in rats. In anesthetized rats, nasociliary (sensory) nerves and postganglionic (parasympathetic) nerves derived from the right sphenopalatine ganglion were electrically stimulated. We measured NBF with a laser-Doppler flowmeter. The nerve stimulation increased NBF on both sides and increased the mean arterial blood pressure. The increase in NBF was larger on the ipsilateral side than on the contralateral side. Hexamethonium bromide, a ganglion blocker, abolished the stimulation-induced pressure effect and the increase in NBF on the contralateral side, but did not abolish the increase in NBF on the ipsilateral side. The remaining increase in NBF was abolished by N(G)-nitro-L-arginine, a nitric oxide synthase inhibitor. Histochemical analysis with nicotinamide adenine dinucleotide phosphate-diaphorase showed neuronal nitric oxide synthase-containing nerves that innervate nasal mucosal arteries. Nitric oxide released from parasympathetic nitrergic nerves may contribute to an increase in NBF in rats. The afferent impulses induced by sensory nerve stimulation may lead to an increase in mean arterial blood pressure that is partly responsible for the increase in NBF.

Lycopene as A Carotenoid Provides Radioprotectant and Antioxidant Effects by Quenching Radiation-Induced Free Radical Singlet Oxygen: An Overview

PubMed Central

Pirayesh Islamian, Jalil; Mehrali, Habib

2015-01-01

Radio-protectors are agents that protect human cells and tissues from undesirable effects of ionizing radiation by mainly scavenging radiation-induced free radicals. Although chemical radio-protectors diminish these deleterious side effects they induce a number of unwanted effects on humans such as blood pressure modifications, vomiting, nausea, and both local and generalized cutaneous reactions. These disadvantages have led to emphasis on the use of some botanical radio-protectants as alternatives. This review has collected and organized studies on a plant-derived radio-protector, lycopene. Lycopene protects normal tissues and cells by scavenging free radicals. Therefore, treatment of cells with lycopene prior to exposure to an oxidative stress, oxidative molecules or ionizing radiation may be an effective approach in diminishing undesirable effects of radiation byproducts. Studies have designated lycopene to be an effective radio-protector with negligible side effects. PMID:25685729

Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice.

PubMed

Refsgaard, Louise K; Pickering, Darryl S; Andreasen, Jesper T

2017-02-01

Evidence suggests that N-methyl-D-aspartate receptor (NMDAR) antagonists could be efficacious in treating depression and anxiety, but side effects constitute a challenge. This study evaluated the antidepressant-like and anxiolytic-like actions, and cognitive and motor side effects of four NMDAR antagonists. MK-801, ketamine, S-ketamine, RO 25-6981 and the positive control, citalopram, were tested for antidepressant-like and anxiolytic-like effects in mice using the forced-swim test, the elevated zero maze and the novelty-induced hypophagia test. Side effects were assessed using a locomotor activity test, the modified Y-maze and the rotarod test. All compounds increased swim distance in the forced-swim test. In the elevated zero maze, the GluN2B subtype-selective RO 25-6981 affected none of the measured parameters, whereas all other compounds showed anxiolytic-like effects. In the novelty-induced hypophagia test, citalopram and MK-801 showed anxiogenic-like action. All NMDAR antagonists induced hyperactivity. The high doses of ketamine and MK-801 impaired performance in the modified Y-maze test, whereas S-ketamine and RO 25-6891 showed no effects in this test. Only MK-801 impaired rotarod performance. The study supports that NMDARs could be a possible therapeutic target for treating depression and anxiety. However, selective antagonism of GluN2B subunit-containing NMDARs showed no effect on anxiety-like behaviours in this study.

Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD.

PubMed

Lee, James; Grizenko, Natalie; Bhat, Venkataramana; Sengupta, Sarojini; Polotskaia, Anna; Joober, Ridha

2011-04-21

The desired (therapeutic) and undesired (side) effects of methylphenidate might have underlying correlations. The aim of this study was to explore the strength and the possible sources of these correlations. One hundred and fifty-seven children with ADHD (6-12 years) were administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose), each for a one-week period, in a double-blind, crossover trial. Therapeutic response was assessed using the Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers), while side effects were assessed using the Barkley Side Effects Rating Scale (SERS). The side effect profile as assessed by the SERS was similar to that of previous studies with insomnia, decreased appetite, and headaches showing significant treatment effects (p < 0.005). These "somatic/physical" side effects did not correlate with CGI-Parents or CGI-Teachers. However, the side effects of "irritability", "proneness to crying", and "anxiousness" showed significant relationships with CGI-Parents. These "mood/anxiety" side effects showed no significant correlations with the CGI-Teachers. The greater "mood/anxiety" side effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate. This suggests that the correlations between "mood/anxiety" side effects and poor response to treatment may be driven by observer effects rather than biological commonalities between therapeutic and side effects of methylphenidate.

Psychiatric effects of antiepileptic drugs in adults.

PubMed

Dussaule, Claire; Bouilleret, Viviane

2018-06-01

Epileptic and psychiatric diseases share overlaps. Indeed, anxiety and depression are common comorbidities in epilepsy, and patients with psychiatric disease are at risk of epilepsy. Some antiepileptic drugs (AED) have psychiatric side effects; conversely, some AED could be used to treat psychiatric pathologies. Based on current literature data, the aim of this study is to determine the psychiatric effects induced by the most frequently prescribed AED in epileptic adults. Some AED will have positive mood or anxiolytic effects like sodium channel blockers, valproate and benzodiazepines; conversely, others might induce negative psychiatric effect, especially depression, anxiety or aggression, like levetiracetam, perampanel, topiramate, zonisamide, and barbiturates. The main risk factor for presenting these side effects is a personal history of psychiatric pathology. We therefore recommend monitoring the occurrence of psychiatric side effects, especially when using the most at risk AED and/or in case of psychiatric history. Moreover, in this latter case, it is preferable to use AED with positive psychiatric effects. The use of anxiety and depression scales could be useful detection tools.

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

PubMed Central

Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects. PMID:28910337

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression.

PubMed

van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.

Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

PubMed

Addington, James; Freimer, Miriam

2016-01-01

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

Clinical efficacy and safety of cisapride and clebopride in the management of chronic functional dyspepsia: a double-blind, randomized study.

PubMed

Sabbatini, F; Minieri, M; Manzi, G; Piai, G; D'Angelo, V; Mazzacca, G

1991-01-01

The clinical efficacy and the safety of chronic oral administration of cisapride, a new gastrointestinal prokinetic agent, (10 mg tid) and clebopride (0.5 mg tid) was assayed in 48 outpatients affected with functional dyspepsia, in a randomized double-blind study. Each of the drugs induced a significant reduction in dyspeptic symptoms after 2 and 4 weeks (p less than 0.001). Two patients, given clebopride, dropped out of the study because of severe side effects during the first week of treatment. Mild adverse reactions were reported in 6 out of 23 cisapride-treated patients and in 10 out of 20 clebopride-treated patients who completed the study. The most common side effect of cisapride was diarrhoea and that of clebopride was drowsiness. Cisapride appears to be as effective as clebopride in reducing dyspeptic symptoms and seems to induce less severe side effects.

Second-generation corticosteroids for the treatment of Crohn's disease and ulcerative colitis: more effective and less side effects?

PubMed

De Cassan, Chiara; Fiorino, Gionata; Danese, Silvio

2012-01-01

Systemic corticosteroids are highly effective at inducing clinical remission in cases of acute exacerbation of Crohn's disease (CD) and ulcerative colitis (UC); however, their use is limited by their frequent and sometimes severe side effects. Thus, a second generation of corticosteroids with less systemic effects has been developed. This review analyzed all of the studies on the new formulations of steroids with limited absorption (budesonide, budesonide MMX®, beclomethasone dipropionate and erythrocyte-mediated delivery of dexamethasone) in patients with CD and UC. All relevant articles published in English between September 1960 and April 2011 were reviewed. Budesonide is superior to placebo, and as effective as systemic corticosteroids in inducing clinical remission in patients with ileo-colonic CD, but evidence of mucosal healing is limited. When administered as an MMX formula, budesonide can also effectively induce clinical remission in patients with UC, but budesonide alone is not effective in maintaining clinical remission in CD or UC. Beclomethasone dipropionate seems to be effective in patients with mild-to-moderate left-sided and extensive UC, while data on erythrocyte-mediated delivery of dexamethasone are encouraging but still limited. The safety profile for all these products is good but more studies are needed. Steroids remain the mainstay for the induction of clinical remission in cases of acute relapse of both CD and UC. Second-generation corticosteroids are an interesting alternative, with the advantage of high topical activity, less systemic toxicity and limited side effects. Copyright © 2012 S. Karger AG, Basel.

New findings in pharmacogenetics of schizophrenia.

PubMed

Zai, Clement C; Tiwari, Arun K; Zai, Gwyneth C; Maes, Miriam S; Kennedy, James L

2018-05-01

This review highlights recent advances in the investigation of genetic factors for antipsychotic response and side effects. Antipsychotics prescribed to treat psychotic symptoms are variable in efficacy and propensity for causing side effects. The major side effects include tardive dyskinesia, antipsychotic-induced weight gain (AIWG), and clozapine-induced agranulocytosis (CIA). Several promising associations of polymorphisms in genes including HSPG2, CNR1, and DPP6 with tardive dyskinesia have been reported. In particular, a functional genetic polymorphism in SLC18A2, which is a target of recently approved tardive dyskinesia medication valbenazine, was associated with tardive dyskinesia. Similarly, several consistent findings primarily from genes modulating energy homeostasis have also been reported (e.g. MC4R, HTR2C). CIA has been consistently associated with polymorphisms in the HLA genes (HLA-DQB1 and HLA-B). The association findings between glutamate system genes and antipsychotic response require additional replications. The findings to date are promising and provide us a better understanding of the development of side effects and response to antipsychotics. However, more comprehensive investigations in large, well characterized samples will bring us closer to clinically actionable findings.

Side effects from intense pulsed light: Importance of skin pigmentation, fluence level and ultraviolet radiation-A randomized controlled trial.

PubMed

Thaysen-Petersen, Daniel; Erlendsson, Andres M; Nash, J F; Beerwerth, Frank; Philipsen, Peter A; Wulf, Hans C; Paasch, Uwe; Haedersdal, Merete

2017-01-01

Intense pulsed light (IPL) is a mainstream treatment for hair removal. Side effects after IPL are known, but risk factors remain to be investigated. The objective of this study was to assess the contribution of skin pigmentation, fluence level, and ultraviolet radiation (UVR) on IPL-induced side effects. The study was a blinded, randomized intra-individual controlled trial including 16 healthy subjects with Fitzpatrick Skin Types (FST) II-V. Three test areas were each divided into four sites, randomized to a single IPL exposure of 22, 34, 46 J/cm 2 or triple stacking of 46 J/cm 2 . Areas were subsequently randomized to no UVR or single solar-simulated UVR exposure of 3 Standard Erythema Dose at 30 minutes or 24 hours after IPL. Each area had a corresponding control, resulting in 15 treatment sites. Follow-up visits were scheduled up to 4 weeks after IPL. Outcome measures were: (i) blinded clinical skin reactions; (ii) objectively measured erythema and pigmentation; (iii) pain measured by visual analog scale (VAS); (iv) histology (H&E, Fontana-Masson); and (v) mRNA-expression of p53. Fifteen subjects with FST II-IV completed the protocol. IPL induced a wide range of skin reactions, including erythema (87% of subjects), purpura (27%), blisters (20%), edema (13%), crusting (13%), hyper- (60%), and hypopigmentation (20%). Darker skin pigmentation and increasing IPL fluence were determinants for IPL-induced side effects (P ≤ 0.002), while a single exposure of UVR did not exacerbate side effects (P ≥ 0.180). Clinical findings were confirmed objectively by reflectance spectrometry and qualitatively by histological changes in skin architecture, inflammatory infiltration, and pigmentation. Marker of cellular DNA damage, that is, p53, did not increase after IPL (P ≥ 0.24). Skin pigmentation and IPL fluence are major determinants of side effects after IPL exposure, while a single exposure to three SED of UVR at 30 minutes or 24 hours after IPL, does not amplify such side effects. Lasers Surg. Med. 49:88-96, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain.

PubMed

Joshi, Gururaj; Sultana, Rukhsana; Tangpong, Jitbanjong; Cole, Marsha Paulette; St Clair, Daret K; Vore, Mary; Estus, Steven; Butterfield, D Allan

2005-11-01

Adriamycin (ADR) is a chemotherapeutic agent useful in treating various cancers. ADR is a quinone-containing anthracycline chemotherapeutic and is known to produce reactive oxygen species (ROS) in heart. Application of this drug can have serious side effects in various tissues, including brain, apart from the known cardiotoxic side effects, which limit the successful use of this drug in treatment of cancer. Neurons treated with ADR demonstrate significant protein oxidation and lipid peroxidation. Patients under treatment with this drug often complain of forgetfulness, lack of concentration, dizziness (collectively called somnolence or sometimes called chemobrain). In this study, we tested the hypothesis that ADR induces oxidative stress in brain. Accordingly, we examined the in vivo levels of brain protein oxidation and lipid peroxidation induced by i.p. injection of ADR. We also measured levels of the multidrug resistance-associated protein (MRP1) in brain isolated from ADR- or saline-injected mice. MRP1 mediates ATP-dependent export of cytotoxic organic anions, glutathione S-conjugates and sulphates. The current results demonstrated a significant increase in levels of protein oxidation and lipid peroxidation and increased expression of MRP1 in brain isolated from mice, 72 h post i.p injection of ADR. These results are discussed with reference to potential use of this redox cycling chemotheraputic agent in the treatement of cancer and its chemobrain side effect in brain.

GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects

PubMed Central

Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; David Leander, J; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R

2013-01-01

Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression. PMID:23303054

Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.

PubMed

Tubbs, R Shane; Salter, E George; Killingsworth, Cheryl; Rollins, Dennis L; Smith, William M; Ideker, Raymond E; Wellons, John C; Blount, Jeffrey P; Oakes, W Jerry

2007-01-01

We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals

PubMed Central

Xu, Junjie; Zheng, Longbo; Chen, Jiang; Sun, Yin; Lin, Hui; Jin, Ren-an; Tang, Minyue; Liang, Xiao; Cai, Xiujun

2017-01-01

Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients. PMID:29022906

Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals.

PubMed

Xu, Junjie; Zheng, Longbo; Chen, Jiang; Sun, Yin; Lin, Hui; Jin, Ren-An; Tang, Minyue; Liang, Xiao; Cai, Xiujun

2017-10-12

Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients.

Hippocampal histone acetylation regulates object recognition and the estradiol-induced enhancement of object recognition

PubMed Central

Zhao, Zaorui; Fan, Lu; Fortress, Ashley M.; Boulware, Marissa I.; Frick, Karyn M.

2012-01-01

Histone acetylation has recently been implicated in learning and memory processes, yet necessity of histone acetylation for such processes has not been demonstrated using pharmacological inhibitors of histone acetyltransferases (HATs). As such, the present study tested whether garcinol, a potent HAT inhibitor in vitro, could impair hippocampal memory consolidation and block the memory-enhancing effects of the modulatory hormone 17β-estradiol (E2). We first showed that bilateral infusion of garcinol (0.1, 1, or 10 μg/side) into the dorsal hippocampus (DH) immediately after training impaired object recognition memory consolidation in ovariectomized female mice. A behaviorally effective dose of garcinol (10 μg/side) also significantly decreased DH HAT activity. We next examined whether DH infusion of a behaviorally subeffective dose of garcinol (1 ng/side) could block the effects of DH E2 infusion on object recognition and epigenetic processes. Immediately after training, ovariectomized female mice received bilateral DH infusions of vehicle, E2 (5 μg/side), garcinol (1 ng/side), or E2 plus garcinol. Forty-eight hours later, garcinol blocked the memory-enhancing effects of E2. Garcinol also reversed the E2-induced increase in DH histone H3 acetylation, HAT activity, and levels of the de novo methyltransferase DNMT3B, as well as the E2-induced decrease in levels of the memory repressor protein histone deacetylase 2 (HDAC2). Collectively, these findings suggest that histone acetylation is critical for object recognition memory consolidation and the beneficial effects of E2 on object recognition. Importantly, this work demonstrates that the role of histone acetylation in memory processes can be studied using a HAT inhibitor. PMID:22396409

The Glasgow antipsychotic side-effects scale for clozapine in inpatients and outpatients with schizophrenia or schizoaffective disorder.

PubMed

Ignjatović Ristić, Dragana; Cohen, Dan; Obradović, Andrea; Nikić-Đuričić, Katarina; Drašković, Marija; Hinić, Darko

2018-02-01

The inconsistency in clinician and patient ratings of clozapine-induced side effects underscore the need to supplement clinician-based estimates of side effects with patient-reported ones. The main aims of the study are validation of the Glasgow antipsychotic side-effects scale for clozapine (GASS-C) in Serbian inpatients/outpatients with schizophrenia or schizo-affective disorder and recommendations for its future use, based on common and rare clozapine-associated side-effects. The GASS-C was administered to 95 outpatients/inpatients diagnosed with schizophrenia, schizoaffective, or chronic psychotic disorder. The scale showed good overall reliability, with an internal consistency coefficient of α = 0.84, an average retest coefficient of rho = 0.76, and a Spearman-Brown coefficient of validity of 0.81. Side effects were absent or mild in 64.2% of the patients, moderate in 31.6%, severe in 4.2%; 14% of the subjects considered their symptoms distressing. The most commonly reported side-effects were drowsiness, thirst, frequent urination, and dry mouth. Women reported more side effects than men, and patients not in a relationship reported significantly fewer side effects than patients in a relationship. Results indicate a weak positive correlation (rho = 0.231; p = .025) between severity of side effects and clozapine dose. The GASS-C showed good psychometric characteristics in clinical population of patients on clozapine. In future studies, clozapine serum concentrations should be measured when using the GASS-C to monitor side effects.

Case Report. Prevention of Clozapine-Induced Granulocytopenia/Agranulocytosis with Granulocyte-Colony Stimulating Factor (G-CSF) in an Intellectually Disabled Patient with Schizophrenia

ERIC Educational Resources Information Center

Rajagopal, G.; Graham, J. G.; Haut, F. F. A.

2007-01-01

Background: While clozapine is an effective treatment for refractory schizophrenia, its use is limited by haematological side effects. Treatment options that allow continued prescription of clozapine by tackling these side effects will greatly aid patients for whom this medication is all too often their only hope of recovery. Method: In this case…

Changes of hypertonic saline-induced masseter muscle pain characteristics, by an infusion of the serotonin receptor type 3 antagonist granisetron.

PubMed

Christidis, Nikolaos; Ioannidou, Kiriaki; Milosevic, Milena; Segerdahl, Märta; Ernberg, Malin

2008-10-01

This study aimed to investigate whether granisetron reduces masseter muscle pain and allodynia induced by hypertonic saline. Fifteen healthy women and 15 age-matched healthy men participated in this randomized, placebo-controlled, double-blinded study. They first received bilateral injections of hypertonic saline into the masseter muscles (internal control). The evoked pain intensity and the pressure-pain threshold (PPT) were recorded during 30 minutes. Granisetron was then injected on one side and placebo (normal saline) on the contralateral side. Two minutes thereafter, the hypertonic saline injections were repeated. Pain and PPT were again recorded. The first injection of hypertonic saline induced pain of similar intensity, duration, and pain area on both sides, but with larger pain area in the women (P = .017). The PPT did not change significantly. The second injection of hypertonic saline induced considerably less pain (62.5%), of shorter duration (44.1%), and of smaller area (77.4%) on the side pretreated with granisetron (P = .005). The PPT was increased on the granisetron side in the men (P = .002). The results of this study show that local injection of a single dose of granisetron attenuates masseter muscle pain induced by hypertonic saline. This article presents the changes of hypertonic saline-induced masseter muscle pain characteristics by infusion of granisetron. It appears that the pain-inducing effect in this experimental pain model is partly due to activation of 5-HT3-receptors. Hence, the results indicate that granisetron might offer a new treatment approach for localized myofascial pain.

A successful renal transplantation for renal failure after dasatinib-induced thrombotic thrombocytopenic purpura in a patient with imatinib-resistant chronic myelogenous leukaemia on nilotinib.

PubMed

Martino, Suella; Daguindau, Etienne; Ferrand, Christophe; Bamoulid, Jamal; Hayette, Sandrine; Nicolini, F-E; Capellier, G; Deconinck, Eric; Larosa, Fabrice

2013-01-01

Second-generation tyrosine kinase inhibitors (TKI2) often induce molecular remission, and prolonged survival with a better tolerance in imatinib-resistant chronic myelogenous leukaemia (CML) patients. We report the case of a CML in first chronic phase who was diagnosed in August 2003 in a young 24 year-old Caucasian woman. Our patient received first imatinib and then dasatinib and nilotinib. Imatinib was well tolerated and she developed TTP/HUS on dasatinib without documented evolution of CML and finally obtained MR5.0 with nilotinib and without any side effect. This case also illustrates the absence of cross-resistance and side-effects between the different TKIs and the feasibility of kidney transplantation associated with a nilotinib treatment of CML allowing a continuing MR5.0 and no further side effects.

How does the side-effect information in patient information leaflets influence peoples' side-effect expectations? A cross-sectional national survey of 18- to 65-year-olds in England.

PubMed

Webster, Rebecca K; Weinman, John; Rubin, G James

2017-12-01

To establish how the terms recommended by the European Commission to describe side-effect risk in patient information leaflets (PILs) influences expectations of side-effects and to identify factors associated with these side-effect expectations. A cross-sectional online survey was carried out by a market research company. Data were collected in England between 18th March and 1st April 2016. A total of 1003 adults aged between 18 and 65. Self-reported expectation that the described side-effects would affect participants if they took the medicine, measured on a likelihood scale from 1 (very unlikely) to 5 (very likely). Participants formed high expectations of side-effects for "very common" and "common" side-effects, with 51.9% and 45.0% of participants rating these as "very likely" or "likely" to happen to them, respectively. This fell to 8.1% for "uncommon," 5.8% for "rare" and 4.1% for "very rare." For each descriptor, higher expectations of side-effects were more associated with women or being from an ethnic minority, or having less education, a household illness, high perceived sensitivity to medicines or negative beliefs about medicines. The current use of verbal descriptors to communicate side-effect risk in PILs leads to high side-effect expectations. These expectations could contribute to nocebo-induced medication side-effects experienced by patients. Additional work is required to identify ways to improve the way risk information is conveyed in PILs. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

[Side effects of the HMG-CoA reductase inhibitors (statins). Lupus erythematosus induced by Atorvastatin therapy].

PubMed

Hydzik, Piotr; Szpak, Dorota

2011-01-01

The paper describes the case of 56 years old woman admitted to the Toxicology Department because of skin lesions, joint and muscle pain and elevated activity of transaminases and creatine phosfokinase as well in biochemical analysis. The symptoms occurred after 6 days of the Atorvastatin therapy. The clinical picture indicated side effects of the hipolipemic therapy, but the presence of the skin lesions suggested drug induced collagenosis (lupus erythrematosus, dermatomyositis). Immunological studies confirmed association with antinuclear antibodies (ANA) and anti-Mi-2 autoantibodies in the serum. Immunosuppressive therapy was ordered with clinical and biochemical improvement.

A nonlinear flow-induced energy harvester by considering effects of fictitious springs

NASA Astrophysics Data System (ADS)

Zhang, Guangcheng; Lin, Yueh-Jaw

2018-01-01

In this paper, a newly proposed energy harvesting approach involving nonlinear coupling effects is demonstrated by utilizing a pair of inducing bluff bodies that are put on both sides of the flag-shaped cantilever beam, and placed in a side-by-side configuration to harvest the energy of the flow. One patch of macro fiber composite is attached to the fixed end of the cantilever beam to facilitate converting the kinetic energy into electric power. It is the first time in recent literature that two fluid dynamic phenomena (i.e. the vortex shedding and the Bernoulli effect) are considered simultaneously in the flow-induced energy harvesting field. The fictitious springs are introduced to explain the nonlinear characteristics of the proposed structure. With the effect of the fictitious springs, the speed range of the flow-induced energy harvester is extended. The proposed structure not only improves the output of the induced-based energy harvester compared to one that has just one cylinder, but can also be utilized in an actual hostile ambient environment. The experimental results for the energy harvester prototype are also investigated. The output power of the energy harvester with two cylinders (D = 25 mm) is measured to be 1.12 μW when the flow speed is 0.325 m s-1 and the center-to-center transverse spacing is 45 mm. This research also delves into the geometric variations of the proposed structure and its optimization.

Pharmacogenetic study of second-generation antipsychotic long-term treatment metabolic side effects (the SLiM Study): rationale, objectives, design and sample description.

PubMed

Pina-Camacho, Laura; Díaz-Caneja, Covadonga M; Saiz, Pilar A; Bobes, Julio; Corripio, Iluminada; Grasa, Eva; Rodriguez-Jimenez, Roberto; Fernández, Miryam; Sanjuán, Julio; García-López, Aurelio; Tapia-Casellas, Cecilia; Álvarez-Blázquez, María; Fraguas, David; Mitjans, Marina; Arias, Bárbara; Arango, Celso

2014-01-01

Weight gain is an important and common side effect of second generation antipsychotics (SGAs). Furthermore, these drugs can induce other side effects associated with higher cardiovascular morbidity and mortality, such as insulin resistance, diabetes or metabolic syndrome. Preliminary studies show that inter-individual genetic differences produce varying degrees of vulnerability to the different SGA-induced side effects. The Second-generation antipsychotic Long-term treatment Metabolic side effects (SLiM) study aims to identify clinical, environmental and genetic factors that explain inter-individual differences in weight gain and metabolic changes in drug-naïve patients after six months of treatment with SGAs. The SLIM study is a multicenter, observational, six-month pharmacogenetic study where a cohort of 307 drug-naïve paediatric and adult patients (age range 8.8-90.1 years) and a cohort of 150 age- and sex- matched healthy controls (7.8-73.2 years) were recruited. This paper describes the rationale, objectives and design of the study and provides a description of the sample at baseline. Results from the SLiM study will provide a better understanding of the clinical, environmental, and genetic factors involved in weight gain and metabolic disturbances associated with SGA treatment. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

Persuading drivers to refrain from speeding: Effects of message sidedness and regulatory fit.

PubMed

Pierro, Antonio; Giacomantonio, Mauro; Pica, Gennaro; Giannini, Anna Maria; Kruglanski, Arie W; Higgins, E Tory

2013-01-01

Building on regulatory fit theory (Higgins, 2000, 2005), we tested whether two-sided ads were more effective than one-sided ads in changing intentions toward driving behavior when message recipients were high in assessment orientation rather than locomotion orientation. In one study either a locomotion or an assessment orientation were situationally induced (Study 1) and in another study these different orientations were chronic predispositions (Study 2). As predicted, both studies found that for participants high in assessment, two-sided ads were more effective than one-sided ads, as reflected in stronger engagement with the persuasive message and stronger intentions to reduce driving speed. In contrast, for participants high in locomotion, one-sided ads were more effective than two-sided ads. There was also evidence that the fit effect on intentions to comply was mediated by strength of engagement with the message. Implications for persuasion concerning driving behaviors are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sedative effect of Clozapine is a function of 5-HT2A and environmental novelty.

PubMed

Joshi, Radhika S; Quadros, Rolen; Drumm, Michael; Ain, Rupasri; Panicker, Mitradas M

2017-01-01

Antipsychotic drugs are the mainstay in the treatment of schizophrenia and bipolar disorder. However, antipsychotics often exhibit sedation or activity suppression among many other side effects, and the factors that influence them remain poorly understood. We now show, using a 5-HT 2A knockout (Htr2a -/- ) mouse, that environmental circumstances can affect suppression of activity induced by the atypical antipsychotic- Clozapine. We observed that Htr2a -/- mice were more resistant to Clozapine-induced suppression of activity (CISA) and this behaviour was dependent on the environment being 'novel'. In their 'home' environment, at identical doses the mice exhibited CISA. Interestingly, the effect of genotype and environmental novelty on CISA could not be extended to the other antipsychotics that were tested, i.e. Haloperidol and Risperidone. Haloperidol-induced activity suppression was independent of context and genotype. Whereas context affected Risperidone-induced activity suppression only in the Htr2a +/+ mice. Furthermore, we observed that caffeine, a stimulant, elicited resistance to CISA similar to that seen in the 'novel' context. Our study establishes a previously unknown interaction between the environmental context, 5-HT 2A and CISA and emphasises the role of non-pharmacological factors such as environment on the effects of the drug, which seem antipsychotic-specific. Our findings should advance the understanding of the side effects of individual antipsychotics and the role of environment to overcome side effects such as sedation. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Transient Three-Dimensional Side Load Analysis of Out-of-Round Film Cooled Nozzles

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Lin, Jeff; Ruf, Joe; Guidos, Mike

2010-01-01

The objective of this study is to investigate the effect of nozzle out-of-roundness on the transient startup side loads. The out-of-roundness could be the result of asymmetric loads induced by hardware attached to the nozzle, asymmetric internal stresses induced by previous tests and/or deformation, such as creep, from previous tests. The rocket engine studied encompasses a regeneratively cooled thrust chamber and a film cooled nozzle extension with film coolant distributed from a turbine exhaust manifold. The computational methodology is based on an unstructured-grid, pressure-based computational fluid dynamics formulation, and a transient inlet history based on an engine system simulation. Transient startup computations were performed with the out-of-roundness achieved by four degrees of ovalization of the nozzle: one perfectly round, one slightly out-of-round, one more out-of-round, and one significantly out-of-round. The computed side load physics caused by the nozzle out-of-roundness and its effect on nozzle side load are reported and discussed.

Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy.

PubMed

Davies, Andrew N; Thompson, Jo

2015-10-05

This is an updated version of the original Cochrane review on parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition. To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction (specifically radiation-induced xerostomia). For this update, we ran searches of the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July 2015. We checked the reference lists of retrieved articles for additional studies, contacted experts in the field for unpublished and ongoing trials, and contacted relevant pharmaceutical companies for unpublished and ongoing trials. The selection criteria for the review were: 1) randomised controlled trials; 2) people suffering from radiation-induced salivary gland dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measure. The two review authors independently collected data from the full-text version of relevant papers including: 1) citation details; 2) participants; 3) interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and 6) quality issues.Due to a lack of appropriate data, we were unable to perform a meta-analysis. In the original review, three studies, including a total of 298 participants, fulfilled the inclusion criteria. All three studies involved the use of pilocarpine hydrochloride. We have included no additional studies in the update of the review; we have excluded eight additional studies.The data suggest that pilocarpine hydrochloride is more effective than placebo and at least as effective as artificial saliva. The response rate was 42% to 51%. The time to response was up to 12 weeks. The overall side effect rate was high, and side effects were the main reason for withdrawal (6% to 15% of participants taking 5 mg three times a day had to withdraw). The side effects were usually the result of generalised parasympathomimetic stimulation (for example sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent. There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.

Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy

PubMed Central

2012-01-01

Background Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic. Methods Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects. Results We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia. Conclusion Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects. PMID:22236378

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes

PubMed Central

Karagiannis, Tom C; Lin, Ann JE; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

2010-01-01

Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer. PMID:20930262

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes.

PubMed

Karagiannis, Tom C; Lin, Ann J E; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

2010-10-01

Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer.

Positive and negative tropic curvature induced by microbeam irradiation of protonemal tip cells of the moss Ceratodon purpureus.

PubMed

Lamparter, T; Kagawa, T; Brücker, G; Wada, M

2004-01-01

The photoreceptor phytochrome mediates tropic responses in protonemata of the moss Ceratodon purpureus. Under standard conditions the tip cells grow towards unilateral red light, or perpendicular to the electrical vector of polarized light. In this study the response of tip cells to partial irradiation of the apical region was analysed using a microbeam apparatus. The fluence response curve gave an unexpected pattern: whereas a 15-min microbeam with light intensities around 3 micro mol m (-2) s (-1) induced a growth curvature towards the irradiated side, higher light intensities around 100 micro mol m (-2) s (-1) caused a negative response, the cells grew away from the irradiated side. This avoidance response is explained by two effects: the light intensity is high enough to induce photoconversion into the active Pfr form of phytochrome, not only on the irradiated but also on the non-irradiated side by stray light. At the same time, the strong light on the irradiated side acts antagonistically to Pfr. As a result of this inhibition, the growth direction is moved to the light-avoiding side. Such a Pfr-independent mechanism might be important for the phototropic response to distinguish between the light-directed and light-avoiding side under unilateral light.

Aripiprazole-induced transient myopia: A rare entity.

PubMed

Praveen Kumar, K V; Chiranjeevi, P; Alam, Md Shahid

2018-01-01

Aripiprazole is a new drug for the treatment of adults with schizophrenia. Ocular side effects of aripiprazole are very rare. Review of literature revealed few cases of aripiprazole-induced myopia. We report a rare case of aripiprazole-induced transient myopia. A 22-year-old female patient presented to the department of psychiatry with worsening of symptoms of schizophrenia and was started on aripiprazole. She presented with complaints of blurring of vision in both eyes for 1 week which started on the 3rd day following the use of aripiprazole. Anterior segment examination revealed a shallow anterior chamber and narrow angles. Intraocular pressure was normal. A diagnosis of aripiprazole-induced acute myopia was made and the treating psychiatrist was advised to stop the medication. At 2-week follow-up, the unaided visual acuity improved to 20/20 in both the eyes. Ophthalmologists should be aware of the myopic shift that may occur as an ocular side effect with aripiprazole.

Chronic cannabinoid CB2 activation reverses paclitaxel neuropathy without tolerance or CB1-dependent withdrawal

PubMed Central

Deng, Liting; Guindon, Josée; Cornett, Benjamin L.; Makriyannis, Alexandros; Mackie, Ken; Hohmann, Andrea G.

2014-01-01

Background Mixed cannabinoid CB1/CB2 agonists such as Δ9-tetrahydrocannabinol (Δ9-THC) can produce tolerance, physical withdrawal, and unwanted CB1-mediated central nervous system side effects. Whether repeated systemic administration of a CB2-preferring agonist engages CB1 receptors or produces CB1-mediated side effects is unknown. Methods We evaluated anti-allodynic efficacy, possible tolerance, and cannabimimetic side effects of repeated dosing with a CB2-preferring agonist AM1710 in a model of chemotherapy-induced neuropathy produced by paclitaxel using CB1KO, CB2KO, and WT mice. Comparisons were made with the prototypic classical cannabinoid Δ9-THC. We also explored the site and possible mechanism of action of AM1710. Results Paclitaxel-induced mechanical and cold allodynia developed equivalently in CB1KO, CB2KO, and WT mice. Both AM1710 and Δ9-THC suppressed established paclitaxel-induced allodynia in WT mice. Unlike Δ9-THC, chronic AM1710 did not engage CB1 activity or produce antinociceptive tolerance, CB1-mediated cannabinoid withdrawal, hypothermia, or motor dysfunction. Anti-allodynic efficacy of systemic AM1710 was absent in CB2KO mice or WT mice receiving the CB2 antagonist AM630, administered either systemically or intrathecally. Intrathecal AM1710 also attenuated paclitaxel-induced allodynia in WT but not CB2KO mice, implicating a possible role for spinal CB2 receptors in AM1710 anti-allodynic efficacy. Finally, both acute and chronic treatment with AM1710 decreased mRNA levels of tumor necrosis factor alpha and monocyte chemoattractant protein-1 in lumbar spinal cord of paclitaxel-treated WT mice. Conclusions Our results highlight the potential of prolonged use of CB2 agonists for managing chemotherapy-induced allodynia with a favorable therapeutic ratio marked by sustained efficacy and absence of tolerance, physical withdrawal, or CB1-mediated side effects. PMID:24853387

Side effects induced by the acute levodopa challenge in Parkinson's Disease and atypical parkinsonisms.

PubMed

Vasta, Rosario; Nicoletti, Alessandra; Mostile, Giovanni; Dibilio, Valeria; Sciacca, Giorgia; Contrafatto, Donatella; Cicero, Calogero Edoardo; Raciti, Loredana; Luca, Antonina; Zappia, Mario

2017-01-01

Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40-13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD.

Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function.

PubMed

Kandasamy, Ram; Calsbeek, Jonas J; Morgan, Michael M

2017-01-15

Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior. Intraplantar injection of Complete Freund's Adjuvant (CFA) into the right hindpaw depressed wheel running and caused mechanical allodynia measured with the von Frey test in both male and female rats. Administration of an ED 50 dose of morphine (3.2mg/kg) reversed mechanical allodynia, but did not reverse CFA-induced depression of wheel running. In contrast, administration of a low dose of morphine (1.0mg/kg) restored running for one hour in both sexes, but had no effect on mechanical allodynia. Administration of the atypical opioid buprenorphine had no effect on inflammation-induced depression of wheel running in male or female rats, but attenuated mechanical allodynia in male rats. Administration of buprenorphine and higher doses of morphine depressed wheel running in non-inflamed rats, suggesting that the side effects of opioids interfere with restoration of function. These data indicate that restoration of pain-depressed function requires antinociception in the absence of disruptive side effects. The disruptive side effects of opioids are consistent with the major limitation of opioid use in human pain patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function

PubMed Central

Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior. Intraplantar injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw depressed wheel running and caused mechanical allodynia measured with the von Frey test in both male and female rats. Administration of an ED50 dose of morphine (3.2 mg/kg) reversed mechanical allodynia, but did not reverse CFA-induced depression of wheel running. In contrast, administration of a low dose of morphine (1.0 mg/kg) restored running for one hour in both sexes, but had no effect on mechanical allodynia. Administration of the atypical opioid buprenorphine had no effect on inflammation-induced depression of wheel running in male or female rats, but attenuated mechanical allodynia in male rats. Administration of buprenorphine and higher doses of morphine depressed wheel running in non-inflamed rats, suggesting that the side effects of opioids interfere with restoration of function. These data indicate that restoration of pain-depressed function requires antinociception in the absence of disruptive side effects. The disruptive side effects of opioids are consistent with the major limitation of opioid use in human pain patients. PMID:27746208

Topical 5-Fluorouracil associated skin reaction.

PubMed

Chughtai, Komal; Gupta, Rahul; Upadhaya, Sunil; Al Hadidi, Samer

2017-08-01

Topical 5- Fluorouracil (5-FU) is used more frequently to treat actinic keratosis. We are presenting a skin reaction as a side effect of this medication. Treatment for such cases of 5-FU-induced skin reactions is based on proper skin care and treatment of any superimposed infections. Medical providers should be aware of such side effects to provide their patients with proper instructions to avoid complications.

Side Effects of Virtual Environments: A Review of the Literature

DTIC Science & Technology

2004-05-01

Cybersickness symptoms are the unintended psychophysiological side effects of participation in virtual environments. Symptoms can occur both during...induced motion sickness, cybersickness is believed to result from sensory and perceptual mismatches between the visual and vestibular systems, and can...and the task carried out, can affect either incidence or severity of cybersickness . Taking account of these factors may avoid or minimize symptoms. This

Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine.

PubMed

Altier, N; Stewart, J

1998-04-01

In the present study, we examined the effects of dopamine (DA) receptor antagonists infused into the nucleus accumbens septi (NAS) on analgesia induced by intra-ventral tegmental area (VTA) infusions of the substance P (SP) analog, DiMe-C7 or morphine and intra-NAS infusions of amphetamine. Rats received intra-NAS infusions of either the mixed DA receptor antagonist flupenthixol (1.5 or 3.0 microg/0.5 microl/side; DiMe-C7 only), the DA D1/D5 receptor antagonist SCH 23390 (0.1 microg/0.5 microl/side; DiMe-C7 only) or the DA D2-type receptor antagonist raclopride (1.0, 3.0 or 5.0 microg/0.5 microl/side). Ten minutes later, rats received intra-VTA infusions of DiMe-C7 (3.0 microg/0.5 microl/side) or morphine (3.0 microg/0.5 microl/side) or intra-NAS infusions of amphetamine (2.5 microg/0.5 microl/side). Animals were then administered the formalin test for tonic pain. Intra-NAS raclopride prevented analgesia induced by intra-VTA DiMe-C7, intra-VTA morphine and intra-NAS amphetamine. Similarly, intra-NAS flupenthixol or SCH 23390 attenuated the analgesia induced by intra-VTA DiMe-C7. These findings suggest that tonic pain is inhibited, at least in part, by enhanced DA released from terminals of mesolimbic neurons. Furthermore, the evidence that SP and opioids in the VTA mediate stress-induced analgesia suggests that the pain-suppression system involving the activation of mesolimbic DA neurons is naturally triggered by exposure to stress, pain or both.

Movement Disorders Induced by the "Atypical" Antipsychotic Aripiprazole.

PubMed

Selfani, Karim; Soland, Valérie L; Chouinard, Sylvain; Huot, Philippe

2017-01-01

Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine D2 receptors. Because of its partial agonist activity, it was believed that aripiprazole would be less susceptible than typical antipsychotics to induce extrapyramidal side effects. However, a few case-reports and case-series detailing aripiprazole-induced movement disorders have been published, suggesting that aripiprazole-induced movement disorders may arise. Here, we seek to report further cases of aripiprazole-induced movement disorders to raise the awareness of clinicians on this adverse effect. Patients referred to the André-Barbeau Movement Disorder clinic treated with aripiprazole were enrolled in this study. Their charts were retrospectively reviewed and data regarding past psychiatric history, past antipsychotic medication, duration of aripiprazole treatment, daily dose of aripiprazole administered, and resulting movement disorders were collected. We report 14 cases of parkinsonism, tardive dyskinesia and akathisia induced by aripiprazole. Some of these, mostly the parkinsonian phenotype, abated spontaneously following drug discontinuation, whereas others, mostly related to tardive phenomena, persisted after aripiprazole was discontinued, and required treatment. This case-series adds to the existing literature that suggests that movement disorders may arise following treatment with aripiprazole. Clinicians should be aware of this potential side effect when prescribing aripiprazole to patients.

In Search of a Safe Natural Sleep Aid.

PubMed

Rao, Theertham P; Ozeki, Motoko; Juneja, Lekh R

2015-01-01

Sleep deprivation is associated with an elevated risk of various diseases and leads to a poor quality of life and negative socioeconomic consequences. Sleep inducers such as drugs and herbal medicines may often lead to dependence and other side effects. L-Theanine (γ-glutamylethylamide), an amino acid naturally found abundant in tea leaves, has anxiolytic effects via the induction of α brain waves without additive and other side effects associated with conventional sleep inducers. Anxiolysis is required for the initiation of high-quality sleep. In this study, we review the mechanism(s), safety, and efficacy of L-theanine. Collectively, sleep studies based on an actigraph, the obstructive sleep apnea (OSA) sleep inventory questionnaire, wakeup after sleep onset (WASO) and automatic nervous system (ANS) assessment, sympathetic and parasympathetic nerve activities, and a pediatric sleep questionnaire (PSQ) suggest that the administration of 200 mg of L-theanine before bed may support improved sleep quality not by sedation but through anxiolysis. Because L-theanine does not induce daytime drowsiness, it may be useful at any time of the day. The no observable adverse effect level (NOAEL) for the oral administration of L-theanine was determined to be above 2000 mg/kg bw/day. KEY TEACHING POINTS: Sleep deprivation-associated morbidity is an increasing public health concern posing a substantial socioeconomic burden. Chronic sleep disorders may seriously affect quality of life and may be etiological factors in a number of chronic diseases such as depression, obesity, diabetes, and cardiovascular diseases. Most sleep inducers are sedatives and are often associated with addiction and other side effects. L-Theanine promotes relaxation without drowsiness. Unlike conventional sleep inducers, L-theanine is not a sedative but promotes good quality of sleep through anxiolysis. This review suggests that L-theanine is a safe natural sleep aid.

Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report

PubMed Central

Ho, Vincent; Stewart, Maxwell; Boyd, Peter

2008-01-01

Introduction Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature. Case presentation A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity. Conclusion We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity. PMID:18452597

Oesophagus side effects related to the treatment of oesophageal cancer or radiotherapy of other thoracic malignancies.

PubMed

Adebahr, Sonja; Schimek-Jasch, Tanja; Nestle, Ursula; Brunner, Thomas B

2016-08-01

The oesophagus as a serial organ located in the central chest is frequent subject to "incidental" dose application in radiotherapy for several thoracic malignancies including oesophageal cancer itself. Especially due to the radiosensitive mucosa severe radiotherapy induced sequelae can occur, acute oesophagitis and strictures as late toxicity being the most frequent side-effects. In this review we focus on oesophageal side effects derived from treatment of gastrointestinal cancer and secondly provide an overview on oesophageal toxicity from conventional and stereotactic fractionated radiotherapy to the thoracic area in general. Available data on pathogenesis, frequency, onset, and severity of oesophageal side effects are summarized. Whereas for conventional radiotherapy the associations of applied doses to certain volumes of the oesophagus are well described, the tolerance dose to the mediastinal structures for hypofractionated therapy is unknown. The review provides available attempts to predict the risk of oesophageal side effects from dosimetric parameters of SBRT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antipsychotic-induced akathisia in delirium: A systematic review

PubMed Central

FORCEN, FERNANDO ESPI; MATSOUKAS, KONSTANTINA; ALICI, YESNE

2017-01-01

Objective Akathisia is a neuropsychiatric syndrome characterized by subjective and objective restlessness. It is a common side effect in patients taking antipsychotics and other psychotropics. Patients with delirium are frequently treated with antipsychotic medications that are well known to induce akathisia as a side effect. However, the prevalence, phenomenology, and management of akathisia in patients with delirium remain largely unknown. The purpose of this review was to examine the medical literature in order to establish the current state of knowledge regarding the prevalence of antipsychotic-induced akathisia in patients with delirium. Method A systematic review of the literature was conducted using the EMBASE, MEDLINE, PsycINFO, and CINAHL databases. Some 10 studies addressing the incidence of akathisia in patients taking antipsychotic medication for delirium were identified and included in our review. Results The included studies reported a variable prevalence of antipsychotic-induced akathisia. A higher prevalence was found in patients taking haloperidol. Among atypical antipsychotics, paliperidone and ziprasidone were associated with a higher risk of akathisia. The risk for akathisia appeared to be a dose-related phenomenon. Significance of results Studies using specific scales for evaluation of akathisia in delirium are lacking. Some populations, such as patients with cancer or terminally ill patients in palliative care settings taking antipsychotics for the treatment of delirium, could be at higher risk for development of akathisia as a side effect. PMID:26087817

Hypoxia as a target for tissue specific gene therapy.

PubMed

Rhim, Taiyoun; Lee, Dong Yun; Lee, Minhyung

2013-12-10

Hypoxia is a hallmark of various ischemic diseases such as ischemic heart disease, ischemic limb, ischemic stroke, and solid tumors. Gene therapies for these diseases have been developed with various therapeutic genes including growth factors, anti-apoptotic genes, and toxins. However, non-specific expression of these therapeutic genes may induce dangerous side effects in the normal tissues. To avoid the side effects, gene expression should be tightly regulated in an oxygen concentration dependent manner. The hypoxia inducible promoters and enhancers have been evaluated as a transcriptional regulation tool for hypoxia inducible gene therapy. The hypoxia inducible UTRs were also used in gene therapy for spinal cord injury as a translational regulation strategy. In addition to transcriptional and translational regulations, post-translational regulation strategies have been developed using the HIF-1α ODD domain. Hypoxia inducible transcriptional, translational, and post-translational regulations are useful for tissue specific gene therapy of ischemic diseases. In this review, hypoxia inducible gene expression systems are discussed and their applications are introduced. Copyright © 2013 Elsevier B.V. All rights reserved.

N-acetyl-cysteine prevents toxic oxidative effects induced by IFN-α in human neurons.

PubMed

Alboni, Silvia; Gibellini, Lara; Montanari, Claudia; Benatti, Cristina; Benatti, Stefania; Tascedda, Fabio; Brunello, Nicoletta; Cossarizza, Andrea; Pariante, Carmine M

2013-09-01

Currently IFN-α is widely used for effective treatment of viral infections and several malignancies. However, IFN-α can cause neuropsychiatric disturbances and mental impairments, including fatigue, insomnia, depression, irritability and cognitive deficits. Molecular and cellular mechanisms leading to such side-effects are still poorly understood. Neurons seem to be an important target in mediating cellular effects induced by exposure to this cytokine, but so far little is known about IFN-α-induced effects on these cells. We have investigated the ability of IFN-α (2-100 ng/ml) to induce damage and toxicity to the human neuroblastoma SH-SY5Y cell line, commonly used for studying such phenomena, and the mechanisms underlying these effects. After 24 h treatment, IFN-α increased mitochondrial activity, whereas cell density was reduced in a dose- and time-dependent manner. This effect did not depend on reduced cell proliferation, but rather the activation of apoptosis, as revealed by an increased Bax:Bcl-2 mRNA ratio after 72-h IFN-α exposure. At this time-point, IFN-α also reduced the expression of the brain-derived neurotrophic factor gene, and induced an increase in reactive oxygen species (ROS). A co-treatment with N-acetyl-cysteine (NAC; 5 mm), a potent antioxidant and mitochondrial modulator, was able to counteract all of these IFN-α-induced effects. These findings demonstrated that IFN-α induces neurotoxicity and apoptosis that is, in part, very likely due to mitochondrial damages and production of ROS. We suggest that NAC, already tested for the treatment of psychiatric disorders, may be useful to prevent IFN-α-induced central side-effects in a safe and effective way.

Nephroprotective Effects of Anthocyanin from the Fruits of Panax ginseng (GFA) on Cisplatin-Induced Acute Kidney Injury in Mice.

PubMed

Qi, Zhen-Lan; Wang, Zi; Li, Wei; Hou, Jin-Gang; Liu, Ying; Li, Xin-Dian; Li, Hui-Ping; Wang, Ying-Ping

2017-09-01

Cisplatin is an effective anticancer chemotherapeutic agent, but the use of cisplatin in the clinic is severely limited by side effects. Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy. The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng (GFA) in a murine model of cisplatin-induced acute kidney injury. We observed that pretreatment with GFA attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels and histopathological injury induced by cisplatin. The formation of kidney malondialdehyde, heme oxygenase-1, cytochrome P450 E1 and 4-hydroxynonenal with a concomitant reduction in reduced glutathione was also inhibited by GFA, while the activities of kidney superoxide dismutase and catalase were all increased. GFA also inhibited the increase in serum tumour necrosis factor-α and interleukin-1β induced by cisplatin. In addition, the levels of induced nitric oxide synthase and cyclooxygenase-2 were suppressed by GFA. Furthermore, GFA supplementation inhibited the activation of apoptotic pathways by increasing B cell lymphoma 2 and decreasing Bcl2-associated X protein expression. In conclusion, the findings from the present investigation demonstrate that GFA pre-administration can significantly prevent cisplatin-induced nephrotoxicity, which may be related to its antioxidant, anti-apoptotic and antiinflammatory effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Topical 5-Fluorouracil associated skin reaction

PubMed Central

Chughtai, Komal; Gupta, Rahul; Upadhaya, Sunil

2017-01-01

Abstract Topical 5- Fluorouracil (5-FU) is used more frequently to treat actinic keratosis. We are presenting a skin reaction as a side effect of this medication. Treatment for such cases of 5-FU-induced skin reactions is based on proper skin care and treatment of any superimposed infections. Medical providers should be aware of such side effects to provide their patients with proper instructions to avoid complications. PMID:28845237

Atypical Opioid Mechanisms of Control of Injury-Induced Cutaneous Pain by Delta Receptors

DTIC Science & Technology

2016-07-01

treat, and current opioids (i.e. mu opioid receptor agonists such as morphine) cause unacceptable side effects including addiction . Injuries suffered...treat, and current opioids that act on mu opioid receptors such as morphine generate significant side effects including addiction . War-related...slides. Slides were then processed for fluorescent in situ hybridization with RNAscope technology (ACD Biosystems) to detect Oprd1 mRNA, as described

Influence of intramuscular granisetron on experimentally induced muscle pain by acidic saline.

PubMed

Louca, S; Ernberg, M; Christidis, N

2013-06-01

The aim of this study was to investigate whether intramuscular administration of the 5-HT(3) receptor antagonist granisetron reduces experimental muscle pain induced by repeated intramuscular injections of acidic saline into the masseter muscles. Twenty-eight healthy and pain-free volunteers, fourteen women and fourteen men participated in this randomized, double-blind and placebo-controlled study. After a screening examination and registration of the baseline pressure-pain threshold (PPT), the first simultaneous bilateral injections of 0·5 mL acidic saline (9 mg mL(-1) , pH 3·3) into the masseter muscles were performed. Two days later, PPT and pain (VAS) were re-assessed. The masseter muscle was then pre-treated with 0·5 mL granisetron (Kytril(®) 1 mg mL(-1) pH 5·3) on one side and control substance (isotonic saline, 9 mg mL(-1) pH 6) on the contralateral side. Two minutes thereafter a bilateral simultaneous injection of 0·5 mL acidic saline followed. The evoked pain intensity, pain duration, pain area and PPT were assessed. The volunteers returned 1 week later to re-assess VAS and PPT. On the side pre-treated with granisetron, the induced pain had significantly lower intensity and shorter duration (P < 0·05) compared with the side pre-treated with control. A subgroup analysis showed that the effect of granisetron on pain duration was significant only in women (P < 0·001), while the effect on peak pain and pain area were significant in both sexes. The results showed no significant change in PPT. In conclusion, these results indicate that granisetron has a pain-reducing effect on experimentally induced muscle pain by repeated acidic saline injection. © 2013 John Wiley & Sons Ltd.

Anticancer Effects of Sandalwood (Santalum album).

PubMed

Santha, Sreevidya; Dwivedi, Chandradhar

2015-06-01

Effective management of tumorigenesis requires development of better anticancer agents with greater efficacy and fewer side-effects. Natural products are important sources for the development of chemotherapeutic agents and almost 60% of anticancer drugs are of natural origin. α-Santlol, a sesquiterpene isolated from Sandalwood, is known for a variety of therapeutic properties including anti-inflammatory, anti-oxidant, anti-viral and anti-bacterial activities. Cell line and animal studies reported chemopreventive effects of sandalwood oil and α-santalol without causing toxic side-effects. Our laboratory identified its anticancer effects in chemically-induced skin carcinogenesis in CD-1 and SENCAR mice, ultraviolet-B-induced skin carcinogenesis in SKH-1 mice and in vitro models of melanoma, non-melanoma, breast and prostate cancer. Its ability to induce cell-cycle arrest and apoptosis in cancer cells is its most reported anticancer mechanism of action. The present review discusses studies that support the anticancer effect and the mode of action of sandalwood oil and α-santalol in carcinogenesis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Transporter Protein-Coupled DPCPX Nanoconjugates Induce Diaphragmatic Recovery after SCI by Blocking Adenosine A1 Receptors.

PubMed

Minic, Zeljka; Zhang, Yanhua; Mao, Guangzhao; Goshgarian, Harry G

2016-03-23

Respiratory complications in patients with spinal cord injury (SCI) are common and have a negative impact on the quality of patients' lives. Systemic administration of drugs that improve respiratory function often cause deleterious side effects. The present study examines the applicability of a novel nanotechnology-based drug delivery system, which induces recovery of diaphragm function after SCI in the adult rat model. We developed a protein-coupled nanoconjugate to selectively deliver by transsynaptic transport small therapeutic amounts of an A1 adenosine receptor antagonist to the respiratory centers. A single administration of the nanoconjugate restored 75% of the respiratory drive at 0.1% of the systemic therapeutic drug dose. The reduction of the systemic dose may obviate the side effects. The recovery lasted for 4 weeks (the longest period studied). These findings have translational implications for patients with respiratory dysfunction after SCI. The leading causes of death in humans following SCI are respiratory complications secondary to paralysis of respiratory muscles. Systemic administration of methylxantines improves respiratory function but also leads to the development of deleterious side effects due to actions of the drug on nonrespiratory sites. The importance of the present study lies in the novel drug delivery approach that uses nanotechnology to selectively deliver recovery-inducing drugs to the respiratory centers exclusively. This strategy allows for a reduction in the therapeutic drug dose, which may reduce harmful side effects and markedly improve the quality of life for SCI patients. Copyright © 2016 the authors 0270-6474/16/363441-12$15.00/0.

An efficient mechanism for enhancing the thermoelectricity of nanoribbons by blocking phonon transport in 2D materials.

PubMed

Liu, Yue-Yang; Zeng, Yu-Jia; Jia, Pin-Zhen; Cao, Xuan-Hao; Jiang, Xiangwei; Chen, Ke-Qiu

2018-07-11

Inspired by the novel mechanism of reducing thermal conductivity by local phonon resonance instead of by inducing structural defects, we investigate the effect of side branching on the thermoelectric properties of [Formula: see text] nanoribbons, and prove that side branching is a highly efficient mechanism for enhancing the thermoelectricity of different kinds of nanoribbons. For both armchair and zigzag [Formula: see text] nanoribbons, the side branches result in not only significant blocking of phonon transport but also notable increase of the Seebeck coefficient. Consequently, the thermoelectric figure of merit of the armchair [Formula: see text] nanoribbon is boosted from 0.72 to as high as 1.93, and the originally non-thermoelectric metallic zigzag [Formula: see text] nanoribbon is turned into a thermoelectric material due to the appearance of the band gap induced by the side branches. These results mean that the mechanism of branching is not only very efficient, but also takes effect regardless of the original properties of the nanoribbons, and thus will hold great promise for its application in the thermoelectric field.

Immunization with Small Amyloid-β-derived Cyclopeptide Conjugates Diminishes Amyloid-β-Induced Neurodegeneration in Mice.

PubMed

Mulder, Cornelis K; Dong, Yun; Brugghe, Humphrey F; Timmermans, Hans A M; Tilstra, Wichard; Westdijk, Janny; van Riet, Elly; van Steeg, Harry; Hoogerhout, Peter; Eisel, Ulrich L M

2016-01-01

Soluble oligomeric (misfolded) species of amyloid-β (Aβ) are the main mediators of toxicity in Alzheimer's disease (AD). These oligomers subsequently form aggregates of insoluble fibrils that precipitate as extracellular and perivascular plaques in the brain. Active immunization against Aβ is a promising disease modifying strategy. However, eliciting an immune response against Aβ in general may interfere with its biological function and was shown to cause unwanted side-effects. Therefore, we have developed a novel experimental vaccine based on conformational neo-epitopes that are exposed in the misfolded oligomeric Aβ, inducing a specific antibody response. Here we investigate the protective effects of the experimental vaccine against oligomeric Aβ1-42-induced neuronal fiber loss in vivo. C57BL/6 mice were immunized or mock-immunized. Antibody responses were measured by enzyme-linked immunosorbent assay. Next, mice received a stereotactic injection of oligomeric Aβ1-42 into the nucleus basalis of Meynert (NBM) on one side of the brain (lesion side), and scrambled Aβ1-42 peptide in the contralateral NBM (control side). The densities of choline acetyltransferase-stained cholinergic fibers origination from the NBM were measured in the parietal neocortex postmortem. The percentage of fiber loss in the lesion side was determined relative to the control side of the brain. Immunized responders (79%) showed 23% less cholinergic fiber loss (p = 0.01) relative to mock-immunized mice. Moreover, fiber loss in immunized responders correlated negatively with the measured antibody responses (R2 = 0.29, p = 0.02). These results may provide a lead towards a (prophylactic) vaccine to prevent or at least attenuate (early onset) AD symptoms.

The C-2 derivatives of salvinorin A, ethoxymethyl ether Sal B and β-tetrahydropyran Sal B, have anti-cocaine properties with minimal side effects.

PubMed

Ewald, Amy W M; Bosch, Peter J; Culverhouse, Aimee; Crowley, Rachel Saylor; Neuenswander, Benjamin; Prisinzano, Thomas E; Kivell, Bronwyn M

2017-08-01

Kappa-opioid receptor (KOPr) agonists have pre-clinical anti-cocaine and analgesic effects. However, side effects including sedation, dysphoria, aversion, anxiety and depression limit their therapeutic development. The unique structure of salvinorin A has been used to develop longer acting KOPr agonists. We evaluate two novel C-2 analogues of salvinorin A, ethoxymethyl ether Sal B (EOM Sal B) and β-tetrahydropyran Sal B (β-THP Sal B) alongside U50,488 for their ability to modulate cocaine-induced behaviours and side effects, pre-clinically. Anti-cocaine properties of EOM Sal B were evaluated using the reinstatement model of drug seeking in self-administering rats. EOM Sal B and β-THP Sal B were evaluated for effects on cocaine-induced hyperactivity, spontaneous locomotor activity and sucrose self-administration. EOM Sal B and β-THP Sal B were evaluated for aversive, anxiogenic and depressive-like effects using conditioned place aversion (CPA), elevated plus maze (EPM) and forced swim tests (FSTs), respectively. EOM Sal B (0.1, 0.3 mg/kg, intraperitoneally (i.p.)) dose dependently attenuated drug seeking, and EOM Sal B (0.1 mg/kg, i.p.) and β-THP Sal B (1 mg/kg, i.p.) attenuated cocaine-induced hyperactivity. No effects on locomotor activity, open arm times (EPM) or swimming behaviours (FST) were seen with EOM (0.1 or 0.3 mg/kg, i.p.) or β-THP Sal B (1 or 2 mg/kg, i.p.). However, β-THP Sal B decreased time spent in the drug-paired chamber. EOM Sal B is more potent than Sal A and β-THP Sal B in reducing drug-seeking behaviour with fewer side effects. EOM Sal B showed no effects on sucrose self-administration (0.1 mg/kg), locomotor, depressive-like, aversive-like or anxiolytic effects.

Assessing the role of metabotropic glutamate receptor 5 in multiple nociceptive modalities.

PubMed

Zhu, Chang Z; Wilson, Sonya G; Mikusa, Joseph P; Wismer, Carol T; Gauvin, Donna M; Lynch, James J; Wade, Carrie L; Decker, Michael W; Honore, Prisca

2004-12-15

Preclinical data, performed in a limited number of pain models, suggest that functional blockade of metabotropic glutamate (mGlu) receptors may be beneficial for pain management. In the present study, effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective mGlu5 receptor antagonist, were examined in a wide variety of rodent nociceptive and hypersensitivity models in order to fully characterize the potential analgesic profile of mGlu5 receptor blockade. Effects of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), as potent and selective as MPEP at mGlu5/mGlu1 receptors but more selective than MPEP at N-methyl-aspartate (NMDA) receptors, were also evaluated in selected nociceptive and side effect models. MPEP (3-30 mg/kg, i.p.) produced a dose-dependent reversal of thermal and mechanical hyperalgesia following complete Freund's adjuvant (CFA)-induced inflammatory hypersensitivity. Additionally, MPEP (3-30 mg/kg, i.p.) decreased thermal hyperalgesia observed in carrageenan-induced inflammatory hypersensitivity without affecting paw edema, abolished acetic acid-induced writhing activity in mice, and was shown to reduce mechanical allodynia and thermal hyperalgesia observed in a model of post-operative hypersensitivity and formalin-induced spontaneous pain. Furthermore, at 30 mg/kg, i.p., MPEP significantly attenuated mechanical allodynia observed in three neuropathic pain models, i.e. spinal nerve ligation, sciatic nerve constriction and vincristine-induced neuropathic pain. MTEP (3-30 mg/kg, i.p.) also potently reduced CFA-induced thermal hyperalgesia. However, at 100 mg/kg, i.p., MPEP and MTEP produced central nerve system (CNS) side effects as measured by rotarod performance and exploratory locomotor activity. These results suggest a role for mGlu5 receptors in multiple nociceptive modalities, though CNS side effects may be a limiting factor in developing mGlu5 receptor analgesic compounds.

Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

PubMed

Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

2017-08-01

Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

Antipsychotics side effects' influence on stigma of mental illness: focus group study results.

PubMed

Novak, Lan; Svab, Vesna

2009-03-01

Little research was done on the influence of antipsychotics' side effects on stigma of mental illness. An overview of studies shows that people with mental illness state that because of medication side effects they feel discriminated in the field of employment, observe worsening of family relations and tend to skip or discontinue their regular medication. It is difficult to discriminate between stigmatizing effects of antipsychotics and other stigma related factors such as illness symptoms. A focus group of ten patients with schizophrenia or schizoaffective disorder with severe and remitting mental illness treated with antipsychotic medication was conducted to obtain their personal views on how side effects of antipsychotic drugs affect their everyday lives and contribute to the stigmatization because of mental illness. The patients felt most stigmatized in areas of employment and occupation. They repeatedly skipped or discontinued regular medication due to side effects. Their families supported them throughout treatment and recovery despite problems associated with psychotropic medication. Medication induced stigma affects patients' lives in substantial ways and therefore merits further research, part of which is the patients' personal experience.

Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports

PubMed Central

Aydin, Memduha; Ilhan, Bilge Cetin; Calisir, Saliha; Yildirim, Seda; Eren, Ibrahim

2016-01-01

Objective: Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. Methods: We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia Results: We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. Conclusion: Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine. PMID:26913176

Safety evaluation of lubiprostone in the treatment of constipation and irritable bowel syndrome.

PubMed

Chamberlain, Sherman M; Rao, Satish S C

2012-09-01

Lubiprostone is approved in the United States for the treatment of chronic idiopathic constipation and constipation predominant irritable bowel syndrome (IBS-C). Lubiprostone causes secretion of fluid and electrolytes in the small bowel, through the activation of chloride channels, and thereby induces laxation and improvement of bowel functions. It is generally considered to be safe and effective. Common side effects of lubiprostone include nausea, diarrhea, abdominal pain and bloating, and the rare side effect dyspnea. Likely mechanisms for these side effects may be related to lubiprostone's primary action on small bowel secretion and the associated intestinal distension, as well as smooth muscle contraction. This article reviews the pharmacokinetic and safety profile of lubiprostone, with particular relevance to the two FDA-approved dosages. Lubiprostone acts topically in the gut lumen and is almost completely metabolized in the gut lumen. Lubiprostone's M3 metabolite can be detected in low concentrations in the serum and may be responsible for some of its side effects. However, the exact mechanisms by which the side effects are produced are currently unknown.

Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports.

PubMed

Aydin, Memduha; Ilhan, Bilge Cetin; Calisir, Saliha; Yildirim, Seda; Eren, Ibrahim

2016-02-01

Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia. We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine.

The effect of acute hypoxia on short-circuit current and epithelial resistivity in biopsies from human colon.

PubMed

Carra, Graciela E; Ibáñez, Jorge E; Saraví, Fernando D

2013-09-01

In isolated colonic mucosa, decreases in short-circuit current (ISC) and transepithelial resistivity (RTE) occur when hypoxia is either induced at both sides or only at the serosal side of the epithelium. We assessed in human colon biopsies the sensitivity to serosal-only hypoxia and mucosal-only hypoxia and whether Na, K-ATPase blockade with ouabain interacts with hypoxia. Biopsy material from patients undergoing colonoscopy was mounted in an Ussing chamber for small samples (1-mm2 window). In a series of experiments we assessed viability and the electrical response to the mucolytic, dithiothreitol (1 mmol/l). In a second series, we explored the effect of hypoxia without and with ouabain. In a third series, we evaluated the response to a cycle of hypoxia and reoxygenation induced at the serosal or mucosal side while keeping the oxygenation of the opposite side. 1st series: Dithiothreitol significantly decreased the unstirred layer and ISC but increased RTE. 2nd series: Both hypoxia and ouabain decreased ISC, but ouabain increased RTE and this effect on RTE prevailed even during hypoxia. 3rd series: Mucosal hypoxia caused lesser decreases of ISC and RTE than serosal hypoxia; in the former, but not in the latter, recovery was complete upon reoxygenation. In mucolytic concentration, dithiothreitol modifies ISC and RTE. Oxygen supply from the serosal side is more important to sustain ISC and RTE in biopsy samples. The different effect of hypoxia and Na, K-ATPase blockade on RTE suggests that their depressing effect on ISC involves different mechanisms.

Comparison between basal and apical dendritic spines in estrogen-induced rapid spinogenesis of CA1 principal neurons in the adult hippocampus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murakami, Gen; Mukai, Hideo; Hojo, Yasushi

2006-12-15

Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Here, we demonstrated the rapid effect of 17{beta}-estradiol on the density and morphology of spines in the stratum oriens (s.o., basal side) and in the stratum lacunosum-moleculare (s.l.m., apical side) by imaging Lucifer Yellow-injected CA1 neurons in adult male rat hippocampal slices, because spines in s.o. and s.l.m. have been poorly understood as compared with spines in the stratum radiatum. The application of 1 nM estradiol-induced a rapid increase in the density of spines of pyramidal neurons within 2 h. This increase by estradiol was blocked by Erkmore » MAP kinase inhibitor and estrogen receptor inhibitor in both regions. Effect of blockade by agonists of AMPA receptors and NMDA receptors was different between s.o. and s.l.m. In both regions, ER{alpha} agonist PPT induced the same enhancing effect of spinogenesis as that induced by estradiol.« less

A hidden Markov model to assess drug-induced sleep fragmentation in the telemetered rat.

PubMed

Diack, C; Ackaert, O; Ploeger, B A; van der Graaf, P H; Gurrell, R; Ivarsson, M; Fairman, D

2011-12-01

Drug-induced sleep fragmentation can cause sleep disturbances either via their intended pharmacological action or as a side effect. Examples of disturbances include excessive daytime sleepiness, insomnia and nightmares. Developing drugs without these side effects requires insight into the mechanisms leading to sleep disturbance. The characterization of the circadian sleep pattern by EEG following drug exposure has improved our understanding of these mechanisms and their translatability across species. The EEG shows frequent transitions between specific sleep states leading to multiple correlated sojourns in these states. We have developed a Markov model to consider the high correlation in the data and quantitatively compared sleep disturbance in telemetered rats induced by methylphenidate, which is known to disturb sleep, and of a new chemical entity (NCE). It was assumed that these drugs could either accelerate or decelerate the transitions between the sleep states. The difference in sleep disturbance of methylphenidate and the NCE were quantitated and different mechanisms of action on rebound sleep were identified. The estimated effect showed that both compounds induce sleep fragmentation with methylphenidate being fivefold more potent compared to the NCE.

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

PubMed Central

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review.

PubMed

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

Leukopenia and neutropenia induced by quetiapine.

PubMed

Cowan, Colin; Oakley, Clare

2007-01-30

Leukopenia and neutropenia are recognised as side effects of antipsychotic medication, notably clozapine. A case is presented in which a female Caucasian patient who had previously developed these side effects with clozapine also developed them with quetiapine in conjunction with semisodium valproate. There was no such reaction to zuclopenthixol, sulpiride, olanzapine and aripiprazole. It is concluded that caution should be exercised when treating with quetiapine especially where there has been neutropenia with a previous antipsychotic agent.

Intrathecal Midazolam as an Adjuvant in Pregnancy-Induced Hypertensive Patients Undergoing an Elective Caesarean Section: A Clinical Comparative Study

PubMed Central

Dodawad, Ravichandra; G. B., Sumalatha; Pandarpurkar, Sandeep; Jajee, Parashuram

2016-01-01

Background A pain-free postoperative period is essential following a caesarean section so new mothers may care for and bond with their neonates. Intrathecal adjuvants are often administered during this procedure to provide significant analgesia, but they may also have bothersome side effects. Intrathecal midazolam produces effective postoperative analgesia with no significant side effects. Objectives This prospective, randomized, double-blind study was designed to compare the analgesic efficacy and safety of intrathecal midazolam vs. plain bupivacaine as an adjunct to bupivacaine in pregnancy-induced hypertension patients scheduled for elective caesarean section. Methods Sixty patients diagnosed with pregnancy-induced hypertension on regular treatment who were scheduled for a caesarean section were randomly allocated into two groups: a control group (Group BC, n = 30) and a midazolam group (Group BM, n = 30). Both groups received 10 mg (2 mL) of 0.5% hyperbaric bupivacaine. Group BC received 0.4 mL of distilled water, while group BM received 0.4 mL (2 mg) of midazolam intrathecally. The duration of postoperative analgesia, analgesic requirements during the first 24 hours after surgery, onset times and durations of sensory and motor blocks, incidence of hypotension, vasopressor requirements, and side effects were recorded. Results Postoperative analgesia was significantly longer in the midazolam group compared to the control group (201.5 minutes vs. 357.6 minutes). The mean onset times of the sensory and motor blocks were significantly faster (P < 0.01) in the midazolam group compared to the control group. The mean times to attain the maximum sensory level and motor blocks were also significantly faster in the midazolam group compared to the control group (P < 0.05). The incidence of hypotension was 6.6% in the midazolam group and 36.6% in the control group, which was highly significant. In addition, the number of patients with side effects was significantly lower in the midazolam group compared to the control group. Conclusions Intrathecal midazolam 2 mg provides significantly longer and effective postoperative analgesia with no side effects. PMID:27847698

Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence.

PubMed

Lambert, M; Conus, P; Eide, P; Mass, R; Karow, A; Moritz, S; Golks, D; Naber, D

2004-11-01

(1) determine which antipsychotic side effects (SE) schizophrenic patients consider the most distressing during treatment with typical antipsychotics, (2) measure the impact of actual and past SE on patients' attitude toward antipsychotics and (3) assess the influence of both on adherence. The 213 schizophrenics, treated with conventional antipsychotics, were recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about type and severity of present and past side effects and their attitude and adherence to antipsychotic treatment. The 82 (39%) patients presented present SE while 131 (61%) did not. Sexual dysfunctions (P < 0.001), extrapyramidal (P < 0.05) and psychic side effects (P < 0.05) were rated as significantly subjectively more distressing than sedation or vegetative side effects. Patients presenting with present SE compared with patients without present SE had a significantly more negative general attitude toward antipsychotics (P < 0.05), were more doubtful about their efficacy (P < 0.01) and were less likely to encourage a relative to take such a medication in case of need (P < 0.001). A regression analysis indicated that nonadherence was mainly influenced by negative general and efficacy attitudes toward antipsychotics and the experience of past or present antipsychotic side effects. All antipsychotic side effects, present or past, can have a durable negative impact on patient's attitude toward antipsychotic treatment and adherence. Non-adherence is mainly determined, among other factors, by these negative attitudes, which are partly influenced by the experience of past or present antipsychotic-induced side effects.

Nanosecond laser-induced ablation and laser-induced shockwave structuring of polymer foils down to sub-μm patterns

NASA Astrophysics Data System (ADS)

Lorenz, P.; Bayer, L.; Ehrhardt, M.; Zimmer, K.; Engisch, L.

2015-03-01

Micro- and nanostructures exhibit a growing commercial interest where a fast, cost-effective, and large-area production is attainable. Laser methods have a great potential for the easy fabrication of surface structures into flexible polymer foils like polyimide (PI). In this study two different concepts for the structuring of polymer foils using a KrF excimer laser were tested and compared: the laser-induced ablation and the laser-induced shock wave structuring. The direct front side laser irradiation of these polymers allows the fabrication of different surface structures. For example: The low laser fluence treatment of PI results in nano-sized cone structures where the cone density can be controlled by the laser parameters. This allows inter alia the laser fabrication of microscopic QR code and high-resolution grey-tone images. Furthermore, the laser treatment of the front side of the polymer foil allows the rear side structuring due to a laserinduced shock wave. The resultant surface structures were analysed by optical and scanning electron microscopy (SEM) as well as white light interferometry (WLI).

Risperidone-induced enuresis in two children with autistic disorder.

PubMed

Hergüner, Sabri; Mukaddes, Nahit Motavalli

2007-08-01

Risperidone appears to be effective in treating behavioral problems in children with autistic disorder. Although increased appetite, weight gain, and sedation are among the most common side effects, risperidone-induced enuresis is rarely reported. We will present two cases with risperidone-induced enuresis, and discuss our findings in the context of current literature. Two children aged 11 and 10 years, diagnosed with autism and mental retardation, have developed new-onset diurnal and nocturnal enuresis respectively on their first and second weeks of risperidone monotherapy (1.5 and 1 mg/day). They did not experience sedation, and their medical history and workup were unremarkable. As enuresis did not resolve spontaneously, we decided to substitute risperidone with olanzapine. Enuresis ceased rapidly after discontinuation of risperidone with no emergence when patients were treated with olanzapine 5 mg/day for a period of 6 months and 1 year, respectively. Although the pathophysiology of antipsychotic-induced enuresis remains unclear, a number of mechanisms including alpha(1)-adrenergic blockade, dopamine blockade, and antimuscarinic effects has been proposed. Olanzapine has lower alpha(1)-adrenergic and dopaminergic blockade properties, thus changing risperidone to olanzapine may be an alternative modality in risperidone-induced enuresis when antipsychotic treatment is crucial. Clinicians should be more vigilant about screening for this side effect, especially in younger population with developmental disabilities.

Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes.

PubMed

Ververis, Katherine; Rodd, Annabelle L; Tang, Michelle M; El-Osta, Assam; Karagiannis, Tom C

2011-12-01

Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid (Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies, involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes. Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination therapies for cancer.

Parecoxib sodium pretreatment reduces myoclonus after etomidate: A prospective, double-blind, randomized clinical trial
.

PubMed

Li, Xiuze; Liu, Jun; Zhou, Mengjun; Zhou, Chaojing

2017-07-01

Myoclonus induced by etomidate during induction of general anesthesia is a common phenomenon. This prospective, randomized, saline-controlled clinical study was performed to evaluate the effect of parecoxib sodium pretreatment on the incidence and severity of etomidate-induced myoclonus. 60 patients, American Society of Anesthesiologists (ASA) physical status I or II, aged 20 to 60 years, who were scheduled to undergo elective laparoscopic cholecystectomy under general anesthesia, were allocated randomly into one of two groups to receive parecoxib sodium 40 mg intravenous (group P, n = 30) or the same volume of saline (group S, n = 30) 30 minutes before administration of etomidate (0.3 mg/kg). Myoclonus was assessed on a scale of 0 - 3. Postoperative side effects were recorded. The two groups were comparable with regard to baseline characteristics. The incidence of myoclonus was significantly lower in the parecoxib sodium group (11/30; 37%) than in the saline group (21/30; 70%) (p < 0.05). The severity of myoclonic movements was also significantly reduced by parecoxib sodium (p < 0.05). There were no significant differences between the two groups with respect to postoperative side effects. Pretreatment with intravenous injection of parecoxib sodium 40 mg significantly reduced the incidence and severity of etomidate-induced myoclonus without significant side effects.
.

Transient Side Load Analysis of Out-of-Round Film-Cooled Nozzle Extensions

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Lin, Jeff; Ruf, Joe; Guidos, Mike

2012-01-01

There was interest in understanding the impact of out-of-round nozzle extension on the nozzle side load during transient startup operations. The out-of-round nozzle extension could be the result of asymmetric internal stresses, deformation induced by previous tests, and asymmetric loads induced by hardware attached to the nozzle. The objective of this study was therefore to computationally investigate the effect of out-of-round nozzle extension on the nozzle side loads during an engine startup transient. The rocket engine studied encompasses a regeneratively cooled chamber and nozzle, along with a film cooled nozzle extension. The computational methodology is based on an unstructured-grid, pressure-based computational fluid dynamics formulation, and transient inlet boundary flow properties derived from an engine system simulation. Six three-dimensional cases were performed with the out-of-roundness achieved by three different degrees of ovalization, elongated on lateral y and z axes: one slightly out-of-round, one more out-of-round, and one significantly out-of-round. The results show that the separation line jump was the primary source of the peak side loads. Comparing to the peak side load of the perfectly round nozzle, the peak side loads increased for the slightly and more ovalized nozzle extensions, and either increased or decreased for the two significantly ovalized nozzle extensions. A theory based on the counteraction of the flow destabilizing effect of an exacerbated asymmetrical flow caused by a lower degree of ovalization, and the flow stabilizing effect of a more symmetrical flow, created also by ovalization, is presented to explain the observations obtained in this effort.

Experimental treatment of antipsychotic-induced movement disorders

PubMed Central

Shireen, Erum

2016-01-01

Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy.

PubMed

Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

2015-08-01

Electroconvulsive therapy (ECT) at conventional current amplitudes (800-900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112-174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST.

Chronic cannabinoid receptor 2 activation reverses paclitaxel neuropathy without tolerance or cannabinoid receptor 1-dependent withdrawal.

PubMed

Deng, Liting; Guindon, Josée; Cornett, Benjamin L; Makriyannis, Alexandros; Mackie, Ken; Hohmann, Andrea G

2015-03-01

Mixed cannabinoid receptor 1 and 2 (CB1 and CB2) agonists such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC) can produce tolerance, physical withdrawal, and unwanted CB1-mediated central nervous system side effects. Whether repeated systemic administration of a CB2-preferring agonist engages CB1 receptors or produces CB1-mediated side effects is unknown. We evaluated antiallodynic efficacy, possible tolerance, and cannabimimetic side effects of repeated dosing with a CB2-preferring agonist AM1710 in a model of chemotherapy-induced neuropathy produced by paclitaxel using CB1 knockout (CB1KO), CB2 knockout (CB2KO), and wild-type (WT) mice. Comparisons were made with the prototypic classic cannabinoid Δ(9)-THC. We also explored the site and possible mechanism of action of AM1710. Paclitaxel-induced mechanical and cold allodynia developed to an equivalent degree in CB1KO, CB2KO, and WT mice. Both AM1710 and Δ(9)-THC suppressed established paclitaxel-induced allodynia in WT mice. In contrast to Δ(9)-THC, chronic administration of AM1710 did not engage CB1 activity or produce antinociceptive tolerance, CB1-mediated cannabinoid withdrawal, hypothermia, or motor dysfunction. Antiallodynic efficacy of systemic administration of AM1710 was absent in CB2KO mice and WT mice receiving the CB2 antagonist AM630, administered either systemically or intrathecally. Intrathecal administration of AM1710 also attenuated paclitaxel-induced allodynia in WT mice, but not CB2KO mice, implicating a possible role for spinal CB2 receptors in AM1710 antiallodynic efficacy. Finally, both acute and chronic administration of AM1710 decreased messenger RNA levels of tumor necrosis factor-α and monocyte chemoattractant protein 1 in lumbar spinal cord of paclitaxel-treated WT mice. Our results highlight the potential of prolonged use of CB2 agonists for managing chemotherapy-induced allodynia with a favorable therapeutic ratio marked by sustained efficacy and absence of tolerance, physical withdrawal, or CB1-mediated side effects. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

RF313, an orally bioavailable neuropeptide FF receptor antagonist, opposes effects of RF-amide-related peptide-3 and opioid-induced hyperalgesia in rodents.

PubMed

Elhabazi, Khadija; Humbert, Jean-Paul; Bertin, Isabelle; Quillet, Raphaelle; Utard, Valérie; Schneider, Séverine; Schmitt, Martine; Bourguignon, Jean-Jacques; Laboureyras, Emilie; Ben Boujema, Meric; Simonnet, Guy; Ancel, Caroline; Simonneaux, Valérie; Beltramo, Massimiliano; Bucher, Bernard; Sorg, Tania; Meziane, Hamid; Schneider, Elodie; Petit-Demoulière, Benoit; Ilien, Brigitte; Bihel, Frédéric; Simonin, Frédéric

2017-05-15

Although opiates represent the most effective analgesics, their use in chronic treatments is associated with numerous side effects including the development of pain hypersensitivity and analgesic tolerance. We recently identified a novel orally active neuropeptide FF (NPFF) receptor antagonist, RF313, which efficiently prevents the development of fentanyl-induced hyperalgesia in rats. In this study, we investigated the properties of this compound into more details. We show that RF313 exhibited a pronounced selectivity for NPFF receptors, antagonist activity at NPFF1 receptor (NPFF1R) subtype both in vitro and in vivo and no major side effects when administered in mice up to 30 mg/kg. When co-administered with opiates in rats and mice, it improved their analgesic efficacy and prevented the development of long lasting opioid-induced hyperalgesia. Moreover, and in marked contrast with the dipeptidic NPFF receptor antagonist RF9, RF313 displayed negligible affinity and no agonist activity (up to 100 μM) toward the kisspeptin receptor. Finally, in male hamster, RF313 had no effect when administered alone but fully blocked the increase in LH induced by RFRP-3, while RF9 per se induced a significant increase in LH levels which is consistent with its ability to activate kisspeptin receptors. Altogether, our data indicate that RF313 represents an interesting compound for the development of therapeutic tools aiming at improving analgesic action of opiates and reducing adverse side effects associated with their chronic administration. Moreover, its lack of agonist activity at the kisspeptin receptor indicates that RF313 might be considered a better pharmacological tool, when compared to RF9, to examine the regulatory roles of RF-amide-related peptides and NPFF1R in reproduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Current perspectives in NSAID-induced gastropathy.

PubMed

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection.

[Investigation of glucocorticoid-induced side effects in patients with autoimmune diseases].

PubMed

Nakajima, Aya; Doki, Kosuke; Homma, Masato; Sagae, Terumi; Saito, Reiko; Ito, Satoshi; Sumida, Takayuki; Kohda, Yukinao

2009-04-01

High dose glucocorticoids (GC) are commonly used for the treatment of autoimmune diseases. The frequencies, occurrence day and dose-dependency for side effects may be different among the events such as diabetes mellitus, hyperlipidemia, infectious disease, osteoporosis, and peptic ulcer. We investigated GC-induced side effects in 68 patients treated with GC for autoimmune diseases. Initial dose of GC (prednisolone equivalent) was 0.67+/-0.35 mg/kg/d. Hypercholesterolemia (66%), hypertension (62%), insomnia (50%), hypertriglyceridemia (44%), excessive appetite (38%), hyperglycemia (18%), digestive symptom (16%), moon-shaped face (13%) and oral candidiasis (12%) were observed in 63 patients treated with GC. Hypercholesterolemia, excessive appetite, digestive symptom, moon-shaped face, and oral candidiasis were associated with the initial dose of prednisolone greater than 0.80 mg/kg/d. Insomnia [median 6 days (range 1-88)], excessive appetite [7 days (2-57)], hypertension [8 days (1-37)], digestive symptom [15 days (1-87)] and hypercholesterolemia [19 days (3-77)] were observed early after 6-19 days starting GC. On the other hand, hypertriglyceridemia [33 days (2-131)], oral candidiasis [35 days (7-52)] and hyperglycemia [60 days (4-134)] were developed after 33-60 days starting GC. Since the frequencies, dose-dependency and occurrence day were different among the side effects of GC, medical staffs including physicians and pharmacists should pay attention such features of the events in the treatment of autoimmune diseases.

An analysis of induced pressure fields in electroosmotic flows through microchannels.

PubMed

Zhang, Yonghao; Gu, Xiao-Jun; Barber, Robert W; Emerson, David R

2004-07-15

Induced pressure gradients are found to cause band-broadening effects which are important to the performance of microfluidic devices, such as capillary electrophoresis and capillary chromatography. An improved understanding of the underlying mechanisms causing an induced pressure gradient in electroosmotic flows is presented. The analysis shows that the induced pressure distribution is the key to understanding the experimentally observed phenomena of leakage flows. A novel way of determining the static pressures at the inlet and outlet of microchannels is also presented that takes account of the pressure losses due to flow contraction and expansion. These commonly neglected pressure losses at the channel entrance and outlet are shown to be important in accurately describing the flow. The important parameters that define the effect of induced pressure on the flows are discussed, which may facilitate the design of improved microfluidic devices. The present model clearly identifies the mechanism behind the experimentally observed leakage flows, which is further confirmed by numerical simulations. Not only can the leakage flow occur from the electric-field-free side channel to the main channel, but also the fluid in the main channel can be attracted into the side channel by the induced pressure gradient. Copyright 2004 Elsevier Inc.

Intrathecal clonidine and bupivacaine have synergistic analgesia for acute thermally or inflammatory-induced pain in rats.

PubMed

Nishiyama, Tomoki; Hanaoka, Kazuo

2004-04-01

We investigated the interaction between spinally administered bupivacaine and clonidine using an animal model of acute and inflammatory pain. Rats implanted with lumbar intrathecal catheters were injected intrathecally with saline (control), bupivacaine (1 to 100 microg), or clonidine (0.1 to 3 microg) and tested for their responses to thermal stimulation to the tail (tail flick test) and subcutaneous formalin injection into the hindpaw (formalin test). The effects of the combination of bupivacaine and clonidine on both stimuli were tested by isobolographic analysis. General behavior and motor function were examined as side effects. The 50% effective doses of bupivacaine and clonidine were significantly smaller when combined compared with each single drug in both the tail flick test (2.82 and 0.11 microg versus 7.1 and 0.29 microg, respectively) and phase 1 (0.24 and 0.009 microg versus 5.7 and 0.15 microg) and phase 2 (0.31 and 0.012 microg versus 3.2 and 0.16 microg) of the formalin test. Side effects were decreased by the combination. These results suggest a favorable combination of intrathecal bupivacaine and clonidine in the management of acute and inflammatory pain. The analgesic interaction between intrathecally administered bupivacaine and clonidine was examined during acute thermal and inflammatory-induced pain in rats. The analgesia produced by the combination of these two drugs was synergistic in both acute thermal and inflammatory induced pain, with a decrease in behavioral side effects.

Tranexamic Acid in the Treatment of Melasma: A Review of the Literature.

PubMed

Perper, Marina; Eber, Ariel Eva; Fayne, Rachel; Verne, Sebastian Hugo; Magno, Robert James; Cervantes, Jessica; ALharbi, Mana; ALOmair, Ibrahim; Alfuraih, Abdulkarem; Nouri, Keyvan

2017-06-01

Melasma is a common acquired pigmentary disorder marked by irregular hyperpigmented macules or patches and most commonly occurs in women of darker skin color. It is a chronic often-relapsing condition that causes negative psychosocial effects in those affected. Current treatments such as hydroquinone, kojic acid, and retinoids, among others, demonstrate variable efficacy and side-effect profiles. We conducted a comprehensive literature review examining the use of tranexamic acid (TA), a well-known anti-fibrinolytic agent, in the treatment of melasma. TA delivered orally, topically, and through physical methods works via the inhibition of ultraviolet (UV)-induced plasmin activity in keratinocytes. Predefined search terms were entered into PubMed. Articles were then independently screened by two authors to include only those written in the English language and relating to human subjects with at least mild melasma. The search identified 28 articles, 15 of which met the criteria for full review. The review revealed that TA treatment for melasma is equally effective or more effective than other standard therapies and may induce fewer side effects. Our comprehensive review suggests that TA may be a promising treatment option for melasma because of its demonstrated effectiveness alone and in combination with other modalities as well as its limited side-effect profile.

Dose-dependent valproate-induced alopecia in patients with mental disorders.

PubMed

Tomita, Takashi; Goto, Hidekazu; Yoshida, Tadashi; Tanaka, Katsuya; Sumiya, Kenji; Kohda, Yukinao

2015-01-01

Drug-induced hair loss may occur as a side effect in patients treated with valproate. However, few studies have reported a relationship between the blood levels of valproate and the occurrence of hair loss. We report three cases of alopecia that occurred in patients who received sodium valproate for mental disorders. In all three cases, alopecia appeared after long-term valproate exposure with a plasma concentration of 100 µg/ml approximately. However, the alopecia resolved in all cases after dose reduction or treatment discontinuation. Therefore, alopecia may develop in patients with chronic exposure to high plasma concentrations of valproate. Based on these findings, we believe that patients with high plasma concentrations of valproate should be closely monitored for the occurrence of side effects, particularly alopecia.

The effects of side-chain-induced disorder on the emission spectra and quantum yields of oligothiophene nano-aggregates. A combined experimental and MD-TDDFT study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Jiyun; Jeon, SuKyung; Kim, Janice J.

2014-07-24

Oligomeric thiophenes are commonly-used components in organic electronics and solar cells. These molecules stack and/or aggregate readily under the processing conditions used to form thin films for these applications, significantly altering their optical and charge-transport properties. To determine how these effects depend on the substitution pattern of the thiophene main chains, nano-aggregates of three sexi-thiophene (6T) oligomers having different alkyl substitution patterns were formed using solvent poisoning techniques and studied using steady-state and time-resolved emission spectroscopy. The results indicate the substantial role played by the side-chain substituents in determining the emissive properties of these species. Both the measured spectral changesmore » and their dependence on substitution are well modeled by combined quantum chemistry and molecular dynamics simulations. The simulations connect the side-chain-induced disorder, which determines the favorable chain packing configurations within the aggregates, with their measured electronic spectra.« less

Nicergoline reverts haloperidol-induced loss of detoxifying-enzyme activity.

PubMed

Vairetti, Mariapia; Ferrigno, Andrea; Canonico, Pier Luigi; Battaglia, Angelo; Bertè, Francantonio; Richelmi, Plinio

2004-11-28

We evaluated the effects of nicergoline on antioxidant defense enzymes (detoxifying enzymes), during chronic treatment with haloperidol in rats. Chronic use of haloperidol (10 weeks, 1.5 mg/kg/day) induces a significant decrease in glutathione reductase, glutathione peroxidase and superoxide dismutase activity, in selected areas of the brain. Co-administration of nicergoline (20 days, 10 mg/kg/day) significantly restored the activity of these enzymes to levels comparable to those observed in control rats. These observations suggest beneficial effects of nicergoline in the prevention and in the treatment of haloperidol-induced side effects.

Mid-trimester induced abortion: a review.

PubMed

Lalitkumar, S; Bygdeman, M; Gemzell-Danielsson, K

2007-01-01

Mid-trimester abortion constitutes 10-15% of all induced abortion. The aim of this article is to provide a review of the current literature of mid-trimester methods of abortion with respect to efficacy, side effects and acceptability. There have been continuing efforts to improve the abortion technology in terms of effectiveness, technical ease of performance, acceptability and reduction of side effects and complications. During the last decade, medical methods for mid-trimester induced abortion have shown a considerable development and have become safe and more accessible. The combination of mifepristone and misoprostol is now an established and highly effective method for termination of pregnancy (TOP). Advantages and disadvantages of medical versus surgical methods are discussed. Randomized studies are lacking, and more studies on pain treatment and the safety of any method used in patients with a previous uterine scar are debated, and data are scarce. Pain management in abortion requires special attention. This review highlights the need for randomized studies to set guidelines for mid-trimester abortion methods in terms of safety and acceptability as well as for better analgesic regimens.

[Drug-induced gynecomastia].

PubMed

Schirren, U; Hinz, B; Schirren, C

1986-01-01

Concerning four own observations by men in the age of 41-69 years it has been reported about the drug-induced gynecomastia. It can be demonstrated that the spironolactone induced gynecomastia disappeared after stopping this drug. The knowledge of such side effects is the condition for a pre-information of the patient at the beginning of therapy. The mode of action of spironolactone is discussed. It is referred about the important role of the disturbance of the relation androgen: estrogens under spironolactone as well as the peripheral antiandrogen effect of this substance.

Role of CFTR in oxidative stress and suicidal death of renal cells during cisplatin-induced nephrotoxicity

PubMed Central

Rubera, I; Duranton, C; Melis, N; Cougnon, M; Mograbi, B; Tauc, M

2013-01-01

The clinical use of the antineoplastic drug cisplatin is limited by its deleterious nephrotoxic side effect. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to renal cell death and irreversible kidney dysfunction. Oxidative stress could be modified by the cystic fibrosis transmembrane conductance regulator protein (CFTR), a Cl− channel not only involved in chloride secretion but as well in glutathione (GSH) transport. Thus, we tested whether the inhibition of CFTR could protect against cisplatin-induced nephrotoxicity. Using a renal proximal cell line, we show that the specific inhibitor of CFTR, CFTRinh-172, prevents cisplatin-induced cell death and apoptosis by modulating the intracellular reactive oxygen species balance and the intracellular GSH concentration. This CFTRinh-172-mediated protective effect occurs without affecting cellular cisplatin uptake or the formation of platinum-DNA adducts. The protective effect of CFTRinh-172 in cisplatin-induced nephrotoxicity was also investigated in a rat model. Five days after receiving a single cisplatin injection (5 mg/kg), rats exhibited renal failure, as evidenced by the alteration of biochemical and functional parameters. Pretreatment of rats with CFTRinh-172 (1 mg/kg) prior to cisplatin injection significantly prevented these deleterious cisplatin-induced nephrotoxic effects. Finally, we demonstrate that CFTRinh-172 does not impair cisplatin-induced cell death in the cisplatin-sensitive A549 cancer cell line. In conclusion, the use of a specific inhibitor of CFTR may represent a novel therapeutic approach in the prevention of nephrotoxic side effects during cisplatin treatment without affecting its antitumor efficacy. PMID:24091660

Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response study.

PubMed

Chen, Jing-Xu; Su, Yun-Ai; Bian, Qing-Tao; Wei, Li-He; Zhang, Rong-Zhen; Liu, Yan-Hong; Correll, Christoph; Soares, Jair C; Yang, Fu-De; Wang, Shao-Li; Zhang, Xiang-Yang

2015-08-01

Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Imidazenil prevention of alprazolam-induced acquisition deficit in patas monkeys is devoid of tolerance

PubMed Central

Auta, James; Guidotti, Alessandro; Costa, Erminio

2000-01-01

The partial allosteric modulators (PAMs) of γ-aminobutyric acid-gated Cl− current intensities at γ-aminobutyric acid type A receptors have high affinity but low intrinsic efficacy on benzodiazepine recognition sites. Unlike the full allosteric modulators (FAM), like alprazolam, triazolam, and diazepam, PAMs are virtually devoid of unwanted side effects, including tolerance. Imidazenil (IMD) is a PAM that elicits potent anxiolytic and anticonvulsant actions in rodents and nonhuman primates and retains its anticonvulsant and anxiolytic effects, even in rodents that are tolerant to FAMs. IMD antagonizes the side effects of FAMs in rodents and nonhuman primates. Using patas monkeys and a multiple schedule with repeated acquisition and performance of chain responses, we report that IMD administration for 17 days antagonized without showing tolerance ALP-induced disruption of acquisition. PMID:10696114

Dysregulation of renal aquaporins and epithelial sodium channel in lithium-induced nephrogenic diabetes insipidus.

PubMed

Nielsen, Jakob; Kwon, Tae-Hwan; Christensen, Birgitte Mønster; Frøkiaer, Jørgen; Nielsen, Søren

2008-05-01

Lithium is used commonly to treat bipolar mood disorders. In addition to its primary therapeutic effects in the central nervous system lithium has a number of side effects in the kidney. The side effects include nephrogenic diabetes insipidus with polyuria, mild sodium wasting, and changes in acid/base balance. These functional changes are associated with marked structural changes in collecting duct cell composition and morphology, likely contributing to the functional changes. Over the past few years, investigations of lithium-induced renal changes have provided novel insight into the molecular mechanisms that are responsible for the disturbances in water, sodium, and acid/base metabolism. This includes dysregulation of renal aquaporins, epithelial sodium channel, and acid/base transporters. This review focuses on these issues with the aim to present this in context with clinically relevant features.

Effects on craniofacial growth and development of unilateral botulinum neurotoxin injection into the masseter muscle.

PubMed

Tsai, Chi-Yang; Chiu, Wan Chi; Liao, Yi-Hsuan; Tsai, Chih-Mong

2009-02-01

The effects of botulinum neurotoxin type A (BoNT/A) on masseter muscles, when injected for cosmetic purposes (volumetric reduction) or treatment of excessive muscle activity (bruxism), have been investigated. However, the full anatomic effects of treatment are not known, particularly with respect to the mandible and relevant anthropometric measurements. The intent of this study was to use unilaterial BoNT/A injections to induce localized masseter atrophy and paresis and then to measure the effects of muscle influence on craniofacial growth and development. Growing male Wistar rats, 30 days old, were studied. The experimental group consisted of 8 rats. One side of the masseter muscle was injected with BoNT/A and the other side of the masseter muscle was injected with saline. The side with BoNT/A belonged to 1 group and the side with saline was the sham group. Three rats without injections was the control. After 45 days, the masseter muscles were dissected and weighed. Dry skulls were prepared, and anthropometric measurements determined. One-way ANOVA showed that the animals maintained their weight in both groups; however, the muscles injected with BoNT/A were smaller than the sham or control muscles. Anthropometric measurements of the bony structures attached to the masseter muscle showed a significant treatment effect. After localized masseter muscle atrophy induced by BoNT/A injection, alterations of craniofacial bone growth and development were seen. The results agree with the functional matrix theory that soft tissues regulate bone growth.

Herbal products and serious side effects: a case of ginseng-induced manic episode.

PubMed

Vázquez, I; Agüera-Ortiz, L F

2002-01-01

Ginseng root extract is a widely used herbal product not devoid of side effects. This report describes the development of manic symptoms after ginseng consumption in a patient with affective disorder. Other potentially harmful side effects of ginseng are also reviewed. A single case report. A 56-year-old woman with previous affective disorder presented a manic episode during ginseng intake. Symptoms disappeared rapidly with low doses of neuroleptics and benzodiazepines after ginseng suppression. Ginseng may produce manic symptoms. A special risk situation seems to be affective patients under antidepressant medication. The case emphasizes the lack of harmlessness of herbal products. Patients should be routinely asked about the use of herbal products and diet supplements.

Improving Adherence to Endocrine Therapy in Women With HR-Positive Breast Cancer.

PubMed

Brockway, Julia P; Shapiro, Charles L

2018-05-15

Aromatase inhibitors (AIs) are the standard treatment for postmenopausal women with hormone receptor-positive breast cancers. One of the most common side effects of AIs is joint pain; it is also the most frequently cited reason for nonadherence and discontinuation before completion of the prescribed treatment course. Nonadherence and, in particular, discontinuation, can lead to increased rates of breast cancer mortality. The prevalence of AI-induced arthralgias is about 50%, and there are several interventions, including switching to a different AI, that can increase adherence. The healthcare professional plays a part in fostering adherence by communicating the side effects of AIs to patients before the initiation of treatment, as well as explaining the strategies for addressing these side effects, should they occur.

Effects of electroconvulsive therapy and magnetic seizure therapy on acute memory retrieval.

PubMed

Polster, Julia D; Kayser, Sarah; Bewernick, Bettina H; Hurlemann, René; Schlaepfer, Thomas E

2015-03-01

Electroconvulsive therapy (ECT) is currently the most effective treatment for severe depression. However, it is frequently associated with negative cognitive side effects. Magnetic seizure therapy (MST) depicts an alternative, although experimental, convulsive treatment for major depression. Initial results suggest comparable antidepressant effects accompanied by a better side effect profile. However, no studies up to now have addressed acute retrieval disruption after MST in comparison to ECT. Therefore, we intended to broaden insight into the side effect profile of MST compared to ECT by examining the disruption of acute verbal memory processes after treatment. Twenty depressed patients were randomly assigned to either MST (10 patients) or ECT (10 patients) treatment. On 2 treatment days and 2 treatment-free days, the patients memorized words using a controlled learning paradigm derived from the Batchelder and Riefer storage retrieval model. Four hours after memorization, the patients were asked to retrieve words freely (delayed recall) and a second time with the help of an additional cue constructed out of a hypernymic category (cued recall). By comparing memory performance on treatment days to control days, treatment-induced memory disruption was evaluated. After ECT, delayed recall was disturbed, whereas after MST, it was not. However, this difference in performance was no longer apparent upon cue application (cued recall). This study demonstrates that ECT-induced acute memory disruption measured by delayed recall is absent after MST, confirming its superior side effect profile. We hope that confirming advantages of MST over ECT will improve therapy options for patients with severe depression.

Effect of Different Ground Scenarios on Flow Structure of a Rotor At Hover Condition

NASA Astrophysics Data System (ADS)

Kocak, Goktug; Nalbantoglu, Volkan; Yavuz, Mehmet Metin

2017-11-01

The ground effect of a scaled model rotor at hover condition was investigated experimentally in a confined environment. Different ground effect scenarios including full, partial, and inclined conditions, compared to out of ground condition, were characterized qualitatively and quantitatively using laser illuminated smoke visualization and Laser Doppler Anemometry measurements. The results indicate that the presence of the ground affects the flow regime near the blade tip by changing the spatial extent and the path of the vortex core. After the impingement of the wake to the ground, highly unsteady and turbulent wake is observed. Both the mean and the root mean square of the induced velocity increase toward the blade tip. In line with this, the spectral power of the dominant frequency in the velocity fluctuations significantly increases toward the blade tip. All these observations are witnessed in all ground effect conditions tested in the present study. Considering the inclined ground effect in particular, it is observed that the mean induced velocities of the high side (mountain) are higher compared to the velocities of the low side (valley) in contrast to the general trend observed in the present study where the ground effect reduces the induced velocity.

[Pregnancy and breastfeeding. Side effects of drugs used in the treatment of thyroid diseases, on the fetus and the newborn].

PubMed

Matos, L; Afonso, A

2003-01-01

The authors allude to the composed anti-thyroid drugs, blocking drugs, iodides, radioactive iodine, lithium carbonate and tyrosine side effects. The most common are composed anti-thyroid drugs and tyrosine. Anti-thyroid drugs risks are related to the tresspassing of the placenta barrier which can induce in goitre and hypothyroidism. Thyroid hormones are also very important for the fetus neural development during the first quarter when they cross the placenta.

[Rare side effects in management of hyperthyroidism. Case report].

PubMed

Sohár, Gábor; Kovács, Mónika; Györkös, Andrea; Gasztonyi, Beáta

2016-05-29

The authors present the case history of a patient suffering from hyperthyroidism. The diagnostic procedures revealed the presence of propylthiouracyl induced vasculitis with renal involvement, that recovered completely after the withdrawal of propylthiouracyl and corticosteroid treatment. Thereafter, the patient was treated with thiamasol, that caused agranulocytosis with fever. After transient litium carbonate therapy a succesful thyreoidectomy was performed. Cumulative serious side effects of antithyroid drugs are rare. This case highlights some of the challenges and complications encountered in the management of hyperthyroidism.

Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome.

PubMed

Sandler, B; Aronson, P

1993-04-01

Yohimbine is an indole alkaloid obtained from the yohimbe tree, a common tree in West Africa. We describe a forty-two-year black man in whom a generalized erythrodermic skin eruption, progressive renal failure, and lupus-like syndrome developed following treatment with the drug, yohimbine. A literature review failed to reveal any reported association of these side effects. We review current information on yohimbine's use in male impotence, reported side effects, and its role as a drug allergen.

Asymmetry in the control of cardiac performance by dorsomedial hypothalamus.

PubMed

Xavier, Carlos Henrique; Beig, Mirza Irfan; Ianzer, Danielle; Fontes, Marco Antônio Peliky; Nalivaiko, Eugene

2013-04-15

Dorsomedial hypothalamus (DMH) plays a key role in integrating cardiovascular responses to stress. We have recently reported greater heart rate responses following disinhibition of the right side of the DMH (R-DMH) in anesthetized rats and greater suppression of stress-induced tachycardia following inhibition of the R-DMH in conscious rats [both compared with similar intervention in the left DMH (L-DMH)], suggesting existence of right/left side asymmetry in controlling cardiac chronotropic responses by the DMH. The aim of the present study was to determine whether similar asymmetry is present for controlling cardiac contractility. In anesthetized rats, microinjections of the GABAA antagonist bicuculline methiodide (BMI; 40 pmol/100 nl) into the DMH-evoked increases in heart rate (HR), left ventricular pressure (LVP), myocardial contractility (LVdP/dt), arterial pressure, and respiratory rate. DMH disinhibition also precipitated multiple ventricular and supraventricular ectopic beats. DMH-induced increases in HR, LVP, LVdP/dt, and in the number of ectopic beats dependent on the side of stimulation, with R-DMH provoking larger responses. In contrast, pressor and respiratory responses did not depend on the side of stimulation. Newly described DMH-induced inotropic responses were rate-, preload- and (largely) afterload-independent; they were mediated by sympathetic cardiac pathway, as revealed by their sensitivity to β-adrenergic blockade. We conclude that recruitment of DMH neurons causes sympathetically mediated positive chronotropic and inotropic effects, and that there is an asymmetry, at the level of the DMH, in the potency to elicit these effects, with R-DMH > L-DMH.

TRPM8 is the Principal Mediator of Menthol-induced Analgesia of Acute and Inflammatory Pain

PubMed Central

Liu, Boyi; Fan, Lu; Balakrishna, Shrilatha; Sui, Aiwei; Morris, John B.; Jordt, Sven-Eric

2013-01-01

Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, while other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol and WS-12 induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively with diminished side effects. PMID:23820004

Current Perspectives in NSAID-Induced Gastropathy

PubMed Central

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P.

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection. PMID:23576851

Emerging Role of Probiotics in the Management of Helicobacter pylori Infection: Histopathologic Perspectives.

PubMed

Emara, Mohamed H; Elhawari, Soha A; Yousef, Salem; Radwan, Mohamed I; Abdel-Aziz, Hesham R

2016-02-01

There is growing evidence from preclinical and clinical studies that emphasizes the efficacy of probiotics in the management of Helicobacter (H) pylori infection; it increased the eradication rate, improved patient clinical manifestations and lowered treatment associated side effects. In this review we documented the potential ability of probiotics to ameliorate H. pylori induced histological features. We searched the available literature for full length articles focusing the role of probiotics on H. pylori induced gastritis from histologic perspectives. Probiotics lowered H. pylori density at the luminal side of epithelium, improved histological inflammatory and activity scores both in the gastric corpus and antrum. This effect persists for long period of time after discontinuation of probiotic supplementation and this is probably through an immune mechanism. The current evidence support the promising role of probiotics in improving H. pylori induced histopathological features both in gastric antrum and corpus and for long periods of time. Because increased density of H. pylori on the gastric mucosa is linked to more severe gastritis and increased incidence of peptic ulcers, we can infer that a reduction of the density might help to decrease the risk of developing pathologies, probably the progression toward atrophic gastritis and gastric adenocarcinoma. These effects together with improving the H. pylori eradication rates and amelioration of treatment related side effects might open the door for probiotics to be added to H. pylori eradication regimens. © 2015 John Wiley & Sons Ltd.

cAMP Stimulates Transepithelial Short-Circuit Current and Fluid Transport Across Porcine Ciliary Epithelium.

PubMed

Cheng, Angela King-Wah; Civan, Mortimer M; To, Chi-Ho; Do, Chi-Wai

2016-12-01

To investigate the effects of cAMP on transepithelial electrical parameters and fluid transport across porcine ciliary epithelium. Transepithelial electrical parameters were determined by mounting freshly isolated porcine ciliary epithelium in a modified Ussing chamber. Similarly, fluid movement across intact ciliary body was measured with a custom-made fluid flow chamber. Addition of 1, 10, and 100 μM 8-Br-cAMP (cAMP) to the aqueous side (nonpigmented ciliary epithelium, NPE) induced a sustained increase in short-circuit current (Isc). Addition of niflumic acid (NFA) to the aqueous surface effectively blocked the cAMP-induced Isc stimulation. The administration of cAMP to the stromal side (pigmented ciliary epithelium, PE) triggered a significant stimulation of Isc only at 100 μM. No additive effect was observed with bilateral application of cAMP. Likewise, forskolin caused a significant stimulation of Isc when applied to the aqueous side. Concomitantly, cAMP and forskolin increased fluid transport across porcine ciliary epithelium, and this stimulation was effectively inhibited by aqueous NFA. Depleting Cl- in the bathing solution abolished the baseline Isc and inhibited the subsequent stimulation by cAMP. Pretreatment with protein kinase A (PKA) blockers (H89/KT5720) significantly inhibited the cAMP- and forskolin-induced Isc responses. Our results suggest that cAMP triggers a sustained stimulation of Cl- and fluid transport across porcine ciliary epithelium; Cl- channels in the NPE cells are potentially a cellular site for this PKA-sensitive cAMP-mediated response.

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

PubMed Central

Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

2015-01-01

Electroconvulsive therapy (ECT) at conventional current amplitudes (800–900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112–174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST. PMID:25920013

Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells.

PubMed

Zhang, Qiu Hua; Wu, Chun Fu; Duan, Lian; Yang, Jing Yu

2008-01-01

Cyclophosphamide (CP), commonly used anti-cancer, induces oxidative stress and is cytotoxic to normal cells. It is very important to choice the protective agent combined CP to reduce the side effects in cancer treatment. Ginsenosides are biological active constituents of Panax ginseng C.A. Meyer that acts as the tonic agent for the cancer patients to reduce the side effects in the clinic application. Because CP is a pro-oxidant agent and induces oxidative stress by the generation of free radicals to decrease the activities of anti-oxidant enzymes, the protective effects of the total saponins from stem and leaf of P. ginseng C.A. Meyer (TSPG) act as an anti-oxidant agent against the decreased anti-oxidant enzymes, the genotoxicity and apoptosis induced by CP was carried out. The alkaline single cell gel electrophoresis was employed to detect DNA damage; flow cytometry assay and AO/EB staining assay were employed to measure cell apoptosis; the enzymatic anti-oxidants (T-SOD, CAT and GPx) and non-enzymatic anti-oxidant (GSH) were measured by the various colorimetric methods. CP induced the significant DNA damage in mouse peripheral lymphocytes in time- and dose-dependent manners, inhibited the activities of T-SOD, GPx and CAT, and decreased the contents of GSH in mouse blood, triggered bone marrow cell apoptosis at 6 and 12h. TSPG significantly reduced CP-induced DNA damages in bone marrow cells and peripheral lymphocyte cells, antagonized CP-induced reduction of T-SOD, GPx, CAT activities and the GSH contents, decreased the bone marrow cell apoptosis induced by CP. TSPG, significantly reduced the genotoxicity of CP in bone marrow cells and peripheral lymphocyte cells, and decreased the apoptotic cell number induced by CP in bone marrow cells. The effects of TSPG on T-SOD, GPx, CAT activities and GSH contents might partially contribute to its protective effects on CP-induced cell toxicities.

Thermal analysis of a diffusion bonded Er3+,Yb3+:glass/Co2+: MgAl2O4 microchip lasers

NASA Astrophysics Data System (ADS)

Belghachem, Nabil; Mlynczak, Jaroslaw; Kopczynski, krzysztof; Mierczyk, Zygmunt; Gawron, Michal

2016-10-01

The analysis of thermal effects in a diffusion bonded Er3+,Yb3+:glass/Co2+:MgAl2O4 microchip laser is presented. The analysis is performed for both wavelengths at 940 nm and at 975 nm as well as for two different sides of pumping, glass side and saturable absorber side. The heat sink effect of Co2+:MgAl2O4, as well as the impact of the thermal expansion and induced stress on the diffusion bonding are emphasised. The best configurations for reducing the temperature peaks, the Von Mises stresses on the diffusion bonding, and the thermal lensing are determined.

A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia.

PubMed

Dibonaventura, Marco; Gabriel, Susan; Dupclay, Leon; Gupta, Shaloo; Kim, Edward

2012-03-20

Antipsychotic medications often have a variety of side effects, however, it is not well understood how the presence of specific side effects correlate with adherence in a real-world setting. The aim of the current study was to examine the relationship between these variables among community-dwelling patients with schizophrenia. Data were analyzed from a 2007-2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (N = 876). The presence of side effects was defined as those in which the patient reported they were at least "somewhat bothered". Adherence was defined as a score of zero on the Morisky Medication Adherence Scale. To assess the relationship between side effects and adherence, individual logistic regression models were fitted for each side effect controlling for patient characteristics. A single logistic regression model assessed the relationship between side effect clusters and adherence. The relationships between adherence and health resource use were also examined. A majority of patients reported experiencing at least one side effect due to their medication (86.19%). Only 42.5% reported complete adherence. Most side effects were associated with a significantly reduced likelihood of adherence. When grouped as side effect clusters in a single model, extra pyramidal symptoms (EPS)/agitation (odds ratio (OR) = 0.57, p = 0.0007), sedation/cognition (OR = 0.70, p = 0.033), prolactin/endocrine (OR = 0.69, p = 0.0342), and metabolic side effects (OR = 0.64, p = 0.0079) were all significantly related with lower rates of adherence. Those who reported complete adherence to their medication were significantly less likely to report a hospitalization for a mental health reason (OR = 0.51, p = 0.0006), a hospitalization for a non-mental health reason (OR = 0.43, p = 0.0002), and an emergency room (ER) visit for a mental health reason (OR = 0.60, p = 0.008). Among patients with schizophrenia, medication side effects are highly prevalent and significantly associated with medication nonadherence. Nonadherence is significantly associated with increased healthcare resource use. Prevention, identification, and effective management of medication-induced side effects are important to maximize adherence and reduce health resource use in schizophrenia.

A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia

PubMed Central

2012-01-01

Background Antipsychotic medications often have a variety of side effects, however, it is not well understood how the presence of specific side effects correlate with adherence in a real-world setting. The aim of the current study was to examine the relationship between these variables among community-dwelling patients with schizophrenia. Methods Data were analyzed from a 2007-2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (N = 876). The presence of side effects was defined as those in which the patient reported they were at least "somewhat bothered". Adherence was defined as a score of zero on the Morisky Medication Adherence Scale. To assess the relationship between side effects and adherence, individual logistic regression models were fitted for each side effect controlling for patient characteristics. A single logistic regression model assessed the relationship between side effect clusters and adherence. The relationships between adherence and health resource use were also examined. Results A majority of patients reported experiencing at least one side effect due to their medication (86.19%). Only 42.5% reported complete adherence. Most side effects were associated with a significantly reduced likelihood of adherence. When grouped as side effect clusters in a single model, extra pyramidal symptoms (EPS)/agitation (odds ratio (OR) = 0.57, p = 0.0007), sedation/cognition (OR = 0.70, p = 0.033), prolactin/endocrine (OR = 0.69, p = 0.0342), and metabolic side effects (OR = 0.64, p = 0.0079) were all significantly related with lower rates of adherence. Those who reported complete adherence to their medication were significantly less likely to report a hospitalization for a mental health reason (OR = 0.51, p = 0.0006), a hospitalization for a non-mental health reason (OR = 0.43, p = 0.0002), and an emergency room (ER) visit for a mental health reason (OR = 0.60, p = 0.008). Conclusions Among patients with schizophrenia, medication side effects are highly prevalent and significantly associated with medication nonadherence. Nonadherence is significantly associated with increased healthcare resource use. Prevention, identification, and effective management of medication-induced side effects are important to maximize adherence and reduce health resource use in schizophrenia. PMID:22433036

The effect of chronic administration of sarizotan, 5-HT1A agonist/D3/D4 ligand, on haloperidol-induced repetitive jaw movements in rat model of tardive dyskinesia.

PubMed

Rosengarten, Helen; Bartoszyk, Gerd D; Quartermain, David; Lin, Yan

2006-03-01

Dyskinesia is the most troublesome side effect in long-term treatment of both Parkinson's disease (PD) and schizophrenia. The 5-HT1A agonist and D3/D4 ligand sarizotan [Bartoszyk, G.D., van Amsterdam, C., Greiner, H.E., Rautenberg, W., Russ, H., Seyfried, C.A., 2004. Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile. J. Neural Transm. 111, 113-126.] is in clinical development for the treatment of PD-associated dyskinesia. Because 5-HT1A agonists are known to counteract antipsychotic-induced motor side effects, sarizotan was investigated for its effects in two rat models of tardive dyskinesia (TD). The acute administration of sarizotan (0.17-13.5 mg/kg i.p.) reduced episodes of SKF 38393-induced repetitive jaw movements (RJM) in rats with a maximal effect at 1.5 mg/kg. In a chronic study, sarizotan (0.04-9 mg/kg/day), administered in the drinking water for 7 weeks during withdrawal from chronic haloperidol treatment (1.5 mg/kg/day), dose-dependently reversed haloperidol-induced RJM, significant at the doses of 1.5 and 9 mg/kg. Agonism at 5-HT1A receptors may be mediating the inhibitory effect of sarizotan on RJM in rat models of tardive dyskinesia.

Is herbal therapy safe in obesity? A case of Apium graveolens (Celery) induced hyperthyroidism.

PubMed

Rouhi-Boroujeni, Hojjat; Hosseini, Masih; Gharipour, Mojgan; Rouhi-Boroujeni, Hamid

2016-09-01

Apium graveolens is one of the well-known herbs used for the treatment of different; however, allergic reactions have been reported after its use. This report aimed to demonstrate the A. graveolens induced hyperthyroidism after its oral consumption for weight loss. Mr. A, 48-year-old, with no history of any thyroid diseases, was diagnosed with hyperthyroidism due to daily consumption of 4 g of dried celery leaves for 45 days. After cessation of consumption and treatment with methimazole, the symptoms remitted. Then, the medication was discontinued when the lab tests and ultrasound were normal and indicated the patient's definite recovery. In 2 months follow up of, he was normal and thyroid-stimulating hormone (TSH), T4, T3, anti-TSH receptor, anti thyroperoxidase and antithyroglobulin were in normal ranges. Hyperthyroidism may be induced by consumption celery. Although many studies have reported side effects such as allergic reactions for this herb, this is the first report of hyperthyroidism induced by celery in which the patient recovered after discontinuing the medication. Therefore, it can be assumed that celery induces hyperthyroidism as a side effect of this herb if it is used for a long term.

Effects of Statins on Skeletal Muscle: A Perspective for Physical Therapists

PubMed Central

Di Stasi, Stephanie L.; MacLeod, Toran D.; Winters, Joshua D.

2010-01-01

Hyperlipidemia, also known as high blood cholesterol, is a cardiovascular health risk that affects more than one third of adults in the United States. Statins are commonly prescribed and successful lipid-lowering medications that reduce the risks associated with cardiovascular disease. The side effects most commonly associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death. Often, these side effects can become apparent during or after strenuous bouts of exercise. Although the mechanisms by which statins affect muscle performance are not entirely understood, recent research has identified some common causative factors. As musculoskeletal and exercise specialists, physical therapists have a unique opportunity to identify adverse effects related to statin use. The purposes of this perspective article are: (1) to review the metabolism and mechanisms of actions of statins, (2) to discuss the effects of statins on skeletal muscle function, (3) to detail the clinical presentation of statin-induced myopathies, (4) to outline the testing used to diagnose statin-induced myopathies, and (5) to introduce a role for the physical therapist for the screening and detection of suspected statin-induced skeletal muscle myopathy. PMID:20688875

Intravenous Lidocaine Infusion to Treat Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Papapetrou, Peter; Kumar, Aashish J; Muppuri, Rudram; Chakrabortty, Shushovan

2015-11-01

Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. Numerous chemoprotective agents and treatments have been used with limited success to treat chemotherapy-induced peripheral neuropathy. We report a case in which a patient presenting with chemotherapy-induced peripheral neuropathy received an IV lidocaine infusion over the course of 60 minutes with complete symptomatic pain relief for a prolonged period of 2 weeks.

Neuroprotective activities of curcumin and quercetin with potential relevance to mitochondrial dysfunction induced by oxaliplatin.

PubMed

Waseem, Mohammad; Parvez, Suhel

2016-03-01

Peripheral neurotoxicity is one of the serious dose-limiting side effects of oxaliplatin (Oxa) when used in the treatment of malignant conditions. It is documented that it elicits major side effects specifically neurotoxicity due to oxidative stress forcing the patients to limit its clinical use in long-term treatment. Oxidative stress has been proven to be involved in Oxa-induced toxicity including neurotoxicity. The mitochondria have recently emerged as targets for anticancer drugs in various kinds of toxicity including neurotoxicity that can lead to neoplastic disease. However, there is paucity of literature involving the role of the mitochondria in mediating Oxa-induced neurotoxicity and its underlying mechanism is still debatable. The purpose of this study was to investigate the dose-dependent damage caused by Oxa on isolated brain mitochondria under in vitro conditions. The study was also designed to investigate the neuroprotective effects of nutraceuticals, curcumin (CMN), and quercetin (QR) on Oxa-induced mitochondrial oxidative stress and respiratory chain complexes in the brain of rats. Oxidative stress biomarkers, levels of nonenzymatic antioxidants, activities of enzymatic antioxidants, and mitochondrial complexes were evaluated against the neurotoxicity induced by Oxa. Pretreatment with CMN and QR significantly replenished the mitochondrial lipid peroxidation levels and protein carbonyl content induced by Oxa. CMN and QR ameliorated altered nonenzymatic and enzymatic antioxidants and complex enzymes of mitochondria. We conclude that CMN and QR, by attenuating oxidative stress as evident by mitochondrial dysfunction, hold promise as agents that can potentially reduce Oxa-induced adverse effects in the brain.

Transient Three-Dimensional Side Load Analysis of Out-of-Round Film Cooled Nozzles

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Lin, Jeff; Ruf, Joe; Guidos, Mike

2010-01-01

The objective of this study is to investigate the effect of nozzle out-of-roundness on the transient startup side loads at a high altitude, with an anchored computational methodology. The out-of-roundness could be the result of asymmetric loads induced by hardware attached to the nozzle, asymmetric internal stresses induced by previous tests, and deformation, such as creep, from previous tests. The rocket engine studied encompasses a regeneratively cooled thrust chamber and a film cooled nozzle extension with film coolant distributed from a turbine exhaust manifold. The computational methodology is based on an unstructured-grid, pressure-based computational fluid dynamics formulation, and a transient inlet history based on an engine system simulation. Transient startup computations were performed with the out-of-roundness achieved by four different degrees of ovalization: one perfectly round, one slightly out-of-round, one more out-of-round, and one significantly out-of-round. The results show that the separation-line-jump is the peak side load physics for the round, slightly our-of-round, and more out-of-round cases, and the peak side load increases as the degree of out-of-roundness increases. For the significantly out-of-round nozzle, however, the peak side load reduces to comparable to that of the round nozzle and the separation line jump is not the peak side load physics. The counter-intuitive result of the significantly out-of-round case is found to be related to a side force reduction mechanism that splits the effect of the separation-line-jump into two parts, not only in the circumferential direction and most importantly in time.

Double side read-out technique for mitigation of radiation damage effects in PbWO 4 crystals

DOE PAGES

Lucchini, Marco Toliman; Auffray, E.; Benaglia, A.; ...

2016-04-18

Test beam results of a calorimetric module based on 3×3×22 cm 3 PbWO 4 crystals, identical to those used in the CMS ECAL Endcaps, read out by a pair of photodetectors coupled to the two opposite sides (front and rear) of each crystal are presented. Nine crystals with different level of induced absorption, from 0 to 20 m -1, have been tested using electrons in the 50–200 GeV energy range. Photomultiplier tubes have been chosen as photodetectors to allow for a precise measurement of highly damaged crystals. The information provided by this double side read-out configuration allows to correct formore » event-by-event fluctuations of the longitudinal development of electromagnetic showers. By strongly mitigating the effect of non-uniform light collection efficiency induced by radiation damage, the double side read-out technique significantly improves the energy resolution with respect to a single side read-out configuration. The non-linearity of the response arising in damaged crystals is also corrected by a double side read-out configuration and the response linearity of irradiated crystals is restored. In high radiation environments at future colliders, as it will be the case for detectors operating during the High Luminosity phase of the Large Hadron Collider, defects can be created inside the scintillator volume leading to a non-uniform response of the calorimetric cell. As a result, the double side read-out technique presented in this study provides a valuable way to improve the performance of calorimeters based on scintillators whose active volumes are characterized by high aspect ratio cells similar to those used in this study.« less

Double side read-out technique for mitigation of radiation damage effects in PbWO 4 crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucchini, Marco Toliman; Auffray, E.; Benaglia, A.

Test beam results of a calorimetric module based on 3×3×22 cm 3 PbWO 4 crystals, identical to those used in the CMS ECAL Endcaps, read out by a pair of photodetectors coupled to the two opposite sides (front and rear) of each crystal are presented. Nine crystals with different level of induced absorption, from 0 to 20 m -1, have been tested using electrons in the 50–200 GeV energy range. Photomultiplier tubes have been chosen as photodetectors to allow for a precise measurement of highly damaged crystals. The information provided by this double side read-out configuration allows to correct formore » event-by-event fluctuations of the longitudinal development of electromagnetic showers. By strongly mitigating the effect of non-uniform light collection efficiency induced by radiation damage, the double side read-out technique significantly improves the energy resolution with respect to a single side read-out configuration. The non-linearity of the response arising in damaged crystals is also corrected by a double side read-out configuration and the response linearity of irradiated crystals is restored. In high radiation environments at future colliders, as it will be the case for detectors operating during the High Luminosity phase of the Large Hadron Collider, defects can be created inside the scintillator volume leading to a non-uniform response of the calorimetric cell. As a result, the double side read-out technique presented in this study provides a valuable way to improve the performance of calorimeters based on scintillators whose active volumes are characterized by high aspect ratio cells similar to those used in this study.« less

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.

Comparison of side effects of pentagastrin test and calcium stimulation test in patients with increased basal calcitonin concentration: the gender-specific differences.

PubMed

Ubl, Philipp; Gincu, Tatiana; Keilani, Mohammad; Ponhold, Lothar; Crevenna, Richard; Niederle, Bruno; Hacker, Marcus; Li, Shuren

2014-08-01

The aim of this study was to compare the side effects of the pentagastrin test and the calcium stimulation test in patients with increased basal calcitonin concentration, especially the gender-specific differences of side effects. A total of 256 patients (123 females and 133 males, mean age of 56 ± 27 years, range 21-83 years) had both pentagastrin and calcium stimulation tests. All patients filled in a questionnaire regarding the side effects within 30 min after completion of the stimulation tests. The differences of side effects between female and male patients as well as between the pentagastrin stimulation test and the calcium stimulation test were evaluated. Warmth feeling was the most frequent occurring side effect in all patients who had both pentagastrin and calcium stimulation tests, followed by nausea, altered gustatory sensation, and dizziness. The incidences of urgency to micturate (p < 0.05) and dizziness (p < 0.05) were significantly increased in the female patients as compared to male patients by calcium stimulation test. Significant higher incidences of urgency to micturate (p < 0.05) and warmth feeling (p < 0.05) were found by calcium stimulation test as compared with those by pentagastrin test in female patients. The incidences of nausea (p < 0.05) and abdominal cramping (p < 0.05) in male patients were significantly higher by pentagastrin stimulation test than by calcium stimulation test. There is a significant gender-specific difference in side effects induced by calcium stimulation test. Female patients have fewer side effects by pentagastrin test than by calcium stimulation test. Male patients may tolerate the calcium stimulation test better than the pentagastrin test.

β-glucans and cholesterol (Review)

PubMed Central

Sima, Petr; Vetvicka, Vaclav

2018-01-01

Hypercholesterolemia is one of primary risk factors of cardiovascular disease, together with metabolic syndrome, hypertension and diabetes. Although progress has been made, the search for novel methods of preventing and treating dyslipidemia is ongoing and current therapies for cardiovascular disease induce various side effects. β-glucans are linear unbranched polysaccharides found in various natural sources, such as mushrooms. Due to their structure they are able to interact with innate immunity receptors, however they also act as dietary fibers in the digestive tract. As there are two forms of β-glucans, insoluble and soluble forms, they are able to interact with lipids and biliary salts in the bowel and consequently reduce cholesterol levels. Therefore, they may be developed as a suitable therapeutic option to treat patients with dyslipidemia, as they are natural molecules that do not induce any significant side effects. The current review discusses the evidence supporting the effects of β-glucans on cholesterol levels. PMID:29393350

Effects of unilatral- and bilateral inhibition of rostral ventral tegmental area and central nucleus of amygdala on morphine-induced place conditioning in male Wistar rat.

PubMed

Mohammadian, Zahra; Sahraei, Hedayat; Meftahi, Gholam Hossein; Ali-Beik, Hengameh

2017-03-01

The rostral ventral tegmental area (VTAR) and central nucleus of amygdala (CeA) are considered the main regions for induction of psychological dependence on abused drugs, such as morphine. The main aim of this study was to investigate the transient inhibition of each right and left side as well as both sides of the VTAR and the CeA by lidocaine (2%) on morphine reward properties using the conditioned place preference (CPP) method. Male Wistar rats (250±20 g) 7 days after recovery from surgery and cannulation were conditioned to morphine (7.5 mg/kg) in CPP apparatus. Five minutes before morphine injection in conditioning phase, lidocaine was administered either uni- or bilaterally into the VTAR (0.25 μL/site) or CeA (0.5 μL/site). The results revealed that lidocaine administration into the left side, but not the right side of the VTAR and the CeA reduced morphine CPP significantly. The reduction was potentiated when lidocaine was injected into both sides of the VTAR and the CeA. The number of compartment crossings was reduced when lidocaine was injected into both sides of the VTAR and the CeA as well as the left side. Rearing was reduced when lidocaine was injected into the right, but not the left side of the VTAR. Sniffing and rearing increased when animals received lidocaine in the right side and reduced in the group that received lidocaine in the left side of the CeA. It was concluded that the right and the left side of VTAR and the CeA play different roles in morphine-induced activity and reward. © 2016 John Wiley & Sons Australia, Ltd.

Antibiotic administration alleviates the aggravating effect of orthodontic force on ligature-induced experimental periodontitis bone loss in mice.

PubMed

Shi, J; Liu, Z; Kawai, T; Zhou, Y; Han, X

2017-08-01

It is recognized that orthodontic force (OF) has an aggravating effect on the progression of destructive periodontitis if periodontitis have not been well controlled. However, the underlying mechanism is not completely clear. This study was to investigate the effect of antibiotic administration on OF-aggravated, ligature-induced experimental periodontitis in mice. C57BL/6 mice (male, 8 wk old) were divided into three groups (n = 8). Silk ligatures (SL) were tied around the maxillary right (group 1) or both (groups 2 and 3) first molars on day 0, removed on day 8 and systemic antibiotics was administered through drinking water (group 3) since day 8. OF was applied on the maxillary right first molars since day 13 (groups 2 and 3). All mice were killed on day 20. Total oral bacteria load was significantly higher in group 2 when compared to group 1 on day 20, whereas such count was greatly reduced in group 3 when antibiotics were administered. Periodontal bone loss was significantly increased on SL side vs. control side in group 1. Periodontal bone loss was significantly increased on OF + SL side vs. SL side in group 2 (p < 0.05) but not in group 3 when systemic antibiotics were administered. Gingival mRNA and protein expressions of receptor activator of nuclear factor kappa-B ligand/osteoprotegerin were significantly increased on OF + SL side vs. SL side in group 2 (p < 0.01) but not in group 3. However, comparable levels of tartrate-resistant acid phosphatase-positive cell formation within periodontal space and tooth movement were observed on OF + SL side in groups 2 and 3. Our results suggest that reduction of oral bacterial load by antibiotic administration alleviate orthodontic force-aggravated periodontitis bone loss. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Antiandrogen gynecomastia: an inescapable harm? Radiotherapy: a simple and efficient solution!].

PubMed

Couke, Philippe A; Jichliski, Patrice; Matzinger, Oscar; Ozsahin, Mahmut; Bulling, Shelley M; Zouhair, Abderrahim

2004-01-01

Anti-androgen induced gynecomastia, resulting from a treatment induced imbalance between oestrogens and androgens, is a frequently encountered side effect in the hormonal treatment of patients with prostatic cancer. One might expect to face an increase in the overall incidence of this side effect in the next-coming years as randomized trials clearly point to the evidence of the therapeutic benefit of anti-androgenic treatment for this prostatic cancer. Gynecomastia is often accompanied by mastodynia and does hamper quality of life. Surgery should be considered for established irreversible gynecomastia characterized by hyalinization and extensive fibrosis. However, radiotherapy is the treatment of choice for gynecomastia at it's early stage, or could eventually be considered as a prophylactic treatment in high risk patients. It is a safe and extremely well tolerated treatment resulting in a high degree of therapeutic success with a demonstrated effect on quality of life as reported in randomized trials. To date no medical treatment is proven effective nor devoid from deleterious effects and licenced for this indication.

Fenofibrate monotherapy-induced rhabdomyolysis in a patient with hypothyroidism: A rare case report and literature review.

PubMed

Wang, Dawei; Wang, Yanqiu

2018-04-01

Fenofibrate is a fibric acid derivative indicated for use in hypertriglyceridemia and mixed dyslipidemia treatment among adults. Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation, which is the most serious and fatal side effect of fenofibrate. The objective of this paper is to discuss fatal side effect of fenofibrate and keep safe medication. A patient with hypothyroidism who presented with rhabdomyolysis during fenofibrate monotherapy for hypertriglyceridemia was reported. Fenofibrate Monotherapy Induced Rhabdomyolysis. Fenofibrate was stopped. Adequate fluid resuscitation, mannitol diuresis, myocardium protection, hepatoprotection and urine alkalinization with sodium bicarbonate were performed. Blood tests were normal and the patient was good and discharged 2 weeks later. 13 cases associated with fenofibrate monotherapy-induced rhabdomyolysis were reviewed, which had been published in the English literature. The severity of fenofibrate muscle toxicity may be the result of the combination of two rhabdomyolysis enhancers, such as hypothyroidism and female gender. To avoid it, strict clinical and laboratory monitoring should be maintained, particularly hypothyroidism. Patients should be informed of possible potentially irreversible effects after taking fibrates.

The dark side of browning.

PubMed

Tamucci, Kirstin A; Namwanje, Maria; Fan, Lihong; Qiang, Li

2018-02-01

The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning. This review aims to highlight the adverse outcomes of both overactive and underactive browning activity, the harmful side effects of browning agents, as well as the molecular brake-switch system that has been proposed to regulate this process. Developing novel strategies that both sustain the metabolic improvements of WAT browning and attenuate the related adverse side effects is therefore essential for unlocking the therapeutic potential of browning agents in the treatment of metabolic diseases.

Warfarin-induced Venous Limb Gangrene

PubMed Central

Grim Hostetler, Sarah; Sopkovich, Jennifer; Dean, Steven

2012-01-01

Warfarin is a commonly used anticoagulant that has been associated with several significant cutaneous side effects, most notably warfarin-induced skin necrosis. A lesser known adverse reaction to warfarin is warfarin-induced venous limb gangrene. Both cutaneous adverse effects share the same pathophysiology, but are clinically quite different. The majority of cases of warfarin-induced venous limb gangrene has been in patients with cancer or heparin-induced thrombocytopenia. However, other hypercoagulable disease states, such as the antiphospholipid antibody syndrome, can be associated with venous limb gangrene. In order to increase recognition of this important condition, the authors report a case of warfarin-induced venous limb gangrene in a patient with presumed antiphospholipid antibody syndrome and review the literature on warfarin-induced venous limb gangrene. PMID:23198012

Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model

PubMed Central

Adamson Barnes, Nicholas S.; Mitchell, Vanessa A.; Kazantzis, Nicholas P.

2015-01-01

Background and Purpose While cannabinoids have been proposed as a potential treatment for neuropathic pain, they have limitations. Cannabinoid receptor agonists have good efficacy in animal models of neuropathic pain; they have a poor therapeutic window. Conversely, selective fatty acid amide hydrolase (FAAH) inhibitors that enhance the endocannabinoid system have a better therapeutic window, but lesser efficacy. We examined whether JZL195, a dual inhibitor of FAAH and monacylglycerol lipase (MAGL), could overcome these limitations. Experimental Approach C57BL/6 mice underwent the chronic constriction injury (CCI) model of neuropathic pain. Mechanical and cold allodynia, plus cannabinoid side effects, were assessed in response to systemic drug application. Key Results JZL195 and the cannabinoid receptor agonist WIN55212 produced dose‐dependent reductions in CCI‐induced mechanical and cold allodynia, plus side effects including motor incoordination, catalepsy and sedation. JZL195 reduced allodynia with an ED50 at least four times less than that at which it produced side effects. By contrast, WIN55212 reduced allodynia and produce side effects with similar ED50s. The maximal anti‐allodynic effect of JZL195 was greater than that produced by selective FAAH, or MAGL inhibitors. The JZL195‐induced anti‐allodynia was maintained during repeated treatment. Conclusions and Implications These findings suggest that JZL195 has greater anti‐allodynic efficacy than selective FAAH, or MAGL inhibitors, plus a greater therapeutic window than a cannabinoid receptor agonist. Thus, dual FAAH/MAGL inhibition may have greater potential in alleviating neuropathic pain, compared with selective FAAH and MAGL inhibitors, or cannabinoid receptor agonists. PMID:26398331

Origin of bending in uncoated microcantilever - Surface topography?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lakshmoji, K.; Prabakar, K.; Tripura Sundari, S., E-mail: sundari@igcar.gov.in

2014-01-27

We provide direct experimental evidence to show that difference in surface topography on opposite sides of an uncoated microcantilever induces bending, upon exposure to water molecules. Examination on opposite sides of the microcantilever by atomic force microscopy reveals the presence of localized surface features on one side, which renders the induced stress non-uniform. Further, the root mean square inclination angle characterizing the surface topography shows a difference of 73° between the opposite sides. The absence of deflection in another uncoated microcantilever having similar surface topography confirms that in former microcantilever bending is indeed induced by differences in surface topography.

Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng Xue; Tamai, Riyoko; Endo, Yasuo

2009-02-15

Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1{beta}, but not TNF{alpha}, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1{beta} production was inhibited by clodronate. Furthermore, caspase-1, amore » promoter of IL-1{beta} production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1{beta} induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1{beta} release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs.« less

Neferine reduces cisplatin-induced nephrotoxicity by enhancing autophagy via the AMPK/mTOR signaling pathway.

PubMed

Li, Hui; Tang, Yuling; Wen, Long; Kong, Xianglong; Chen, Xuelian; Liu, Ping; Zhou, Zhiguo; Chen, Wenhang; Xiao, Chenggen; Xiao, Ping; Xiao, Xiangcheng

2017-03-11

Cisplatin is one of the most effective chemotherapeutic agents; however, its clinical use is limited by serious side effects of which nephrotoxicity is the most important. Nephrotoxicity induced by cisplatin is closely associated with autophagy reduction and caspase activation. In this study, we investigated whether neferine, an autophagy inducer, had a protective effect against cisplatin-induced nephrotoxicity. In an in vitro cisplatin-induced nephrotoxicity model, we determined that neferine was able to induce autophagy and that pretreatment with neferine not only attenuated cisplatin-induced cell apoptosis but further activated cell autophagy. This pro-survival effect was abolished by the autophagic flux inhibitor chloroquine. Furthermore, neferine pretreatment activated the AMPK/mTOR pathway; however, pharmacological inhibition of AMPK abolished neferine-mediated autophagy and nephroprotection against cisplatin-induced apoptosis. Collectively, our findings suggest for the first time the possible protective mechanism of neferine, which is crucial for its further development as a potential therapeutic agent for cisplatin-induced nephrotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Continuous prostaglandin-F 2 infusion for middle-trimester abortion.

PubMed

Lauersen, N H; Wilson, K H

1973-05-26

Induction of midtrimester abortion with a continuous intravenous infusion of prostaglandin (PG) was described by Karim and Filshie and Roth-Brandel et al. in 1970, but the effective dose of PGF2alpha was associated with side effects severely limiting clinical usefulness. Karim and Sharma induced abortion by intravaginal PG, but again this route also seemed complicated by severe side effects. Independent reports followed of successful induction of midtrimester abortion by intraamniotic PGF2alpha and PGE2 with few side effects. Although we also successfully induced abortion in 20 patients with a single intraamniotic instillation of 40 mg PGF2alpha, there is a potential hazard in this method; i.e., PG may leak from the amniotic cavity around the catheter and pass in large quantity into the systemic circulation, resulting in undesirable, severe side effects. A more reasonable and effective method would be to inject the PGF2alpha directly at the target organ, the myometrium, by extraovular administration. Side effects could thus be minimized and effective doses of PG reduced. Such intrauterine extraovular administration of PG has been reported. The incidence of side effects was greatly reduced, although the instillation of PG was required every 1-3 hours and there were some incomplete abortions. The investigation of extraovular PGF2alpha administration for induction of abortion in gestations between 12 and 16 weeks has been especially interesting. The procedure outlined by Wiqvist and Bygdeman and Embrey and Hillier was the 1 that the authors followed initially. 250 mcg PGF2alpha was instilled initially and was followed by 750 mcg in 5 minutes and 1 mg in 30 minutes. 1 mg was then instilled at 6 hour intervals. However, the failure rate with this dosage schedule was quite high. There was a good initial uterine response, but during the administrationsat 12, 18, and 24 hours, the response diminished considerably . The frequency of administration was then increased to every 2-3 hours and the amount instilled was increased to 2-3 mg. Although somewhat more successful than the original dose schedule, this method was also unsatisfactory. It appeared from our results that the closer the injections, the higher the success rate. Thus, a brief case report is presented using continuous extraovular administration of PGF2alpha with a Harvard pump, and the results indicate it is quite satisfactory. The patients complained of very little pain and side effects have been slight. The mean abortion time for 15 patients was 14 hours. The mean time for multiparas, 11.7 hours, was faster than the 15.8 hours for primiparas.

Erlotinib induced target-like purpura.

PubMed

Rungtrakulchai, R; Rerknimitr, P

2014-02-18

Erlotinib is an epidermal growth factor receptor (EGFR) inhibitor, used as a treatment for advanced stage cancer. The most common side effect is cutaneous toxicity including the already known papulopustular reaction. We herein report a case of erlotinib induced target-like purpura, a peculiar cutaneous adverse event. A 57-year-old patient with advanced non-small cell lung cancer was treated by erolotinib 150 mg daily. After taking the drug for three days, an unusual target-like purpura developed on her lower legs. Skin biopsy specimen taken from the lesion revealed an extravasation of erythrocytes in the upper dermis without destruction of blood vessel walls. This skin eruption cleared after the drug was withdrawn and recurred after erlotinib was re-challenged. The mechanism underlying this cutaneous adverse event remains to be elucidated. Physicians should be aware of the rare side effect of this increasingly used drug.

A biotin-triggered genetic switch in mammalian cells and mice.

PubMed

Weber, Wilfried; Lienhart, Cédric; Baba, Marie Daoud-El; Fussenegger, Martin

2009-03-01

Adjustable and reversible transgene expression systems enabling precise control of metabolic pathways and tunable production of specific target proteins have been essential for conditional reprogramming of mammalian cells to achieve progress in basic and applied bioengineering disciplines. Most of the currently available transgene control modalities have been designed to be responsive to clinically licensed pharmacologically active drugs which were expected to prevail in future clinical trials yet raised concerns about side effects when administered long term at subclinical doses. We have chosen vitamin H, also known as biotin, to control target gene transcription in mammalian cells in a potentially side effect-free manner. BirA, the Escherichia coli repressor of the biotin biosynthesis operon, was fused to the Herpes simplex transactivation domain to generate a biotin-dependent transactivator(BIT), which, in the presence of biotin, binds and activates chimeric target promoters (P(BIT)) harboring BirA-specific operator sites 5' of a minimal promoter. Biotin-inducible transgene expression was functional in a variety of rodent, monkey and human cell lines, showed excellent adjustability and reversibility in transgenic Chinese hamster ovary cell lines, provided precise product gene control in standard bioreactor cultures and enabled dose-dependent vitamin H control of a human glycoprotein in mice. The combination of a side effect-free inducer, precise and reversible transcription tunability and broad functionality in different cell types as well as in entire animals represents a unique asset for the use of biotin-inducible transgene control in future gene therapy, tissue engineering and biopharmaceutical manufacturing scenarios.

Do preclinical seizure models preselect certain adverse effects of antiepileptic drugs.

PubMed

Meldrum, Brian

2002-06-01

Classical screening tests (maximal electroshock, MES, and threshold pentylenetetrazol, PTZ) employ non-epileptic rodents and identify antiepileptic drugs (AEDs) with mechanisms of action associated with significant CNS side effects. Thus MES identifies drugs acting on Na+ channels that produce cerebellar toxicity. It may be possible to produce novel AEDs more selectively targeted at voltage-sensitive (VS) ion channels. There is little specific evidence for the likely success of this strategy with subunit selective agents targeted at the different VS Na+ channels. Drugs targeted at specific VS Ca++ channels (T, N, P/Q types) may be useful in generalised seizures. There are many as yet unexplored possibilities relating to K+ channels. GABA related drugs acting on PTZ clonic seizures tend to induce sedation and muscle hypotonia. Studies in mice, particularly with knock-in mutations, but also with subunit selective agents acting via the GABA(A) benzodiazepine site, suggest that it is possible to produce agents which do or do not induce particular side effects (sedative, hypnotic, anxiolytic, muscle relaxant, amnesia, anaesthesia). Whether these findings transfer to man has yet to be established. Acquired epilepsy in rodents (e.g. kindling or spontaneous seizures following chemically- or electrically-induced status epilepticus) or acquired epilepsy in man (following prolonged febrile seizures or traumatic brain injury) is associated with multiple changes in the function and subunit composition of ion channels and receptor molecules. Optimal screening of novel AEDs, both for efficacy and side effects, requires models with receptor and ion channel changes similar to those in the target human syndrome.

Long-term potentiation and depression after unilateral labyrinthectomy in the medial vestibular nucleus of rats.

PubMed

Pettorossi, Vito Enrico; Dutia, Mayank; Frondaroli, Adele; Dieni, Cristina; Grassi, Silvarosa

2003-01-01

We previously demonstrated in rat brainstem slices that high-frequency stimulation (HFS) of the vestibular afferents induces long-term potentiation (LTP) in the ventral part (Vp) of the medial vestibular nucleus (MVN) and long-term depression (LTD) in the dorsal part (Dp). Both LTP and LTD depend on N-methyl-D-aspartate receptor activation, which increases synaptic efficacy; however, in the Dp, LTP reverses to LTD because of the activation of gamma-aminobutyric acid-ergic neurons. Here we show that the probability of inducing long-term effects in the MVN of rat brainstem slices is altered after unilateral labyrinthectomy (UL). In fact, LTP occurs less frequently in the ventral contra-lesional side compared with sham-operated rats. In the dorsal ipsi-lesional side, LTD is reduced and LTP enhanced, while the opposite occurs in the dorsal contra-lesional side. These changes in synaptic plasticity may be useful for re-balancing the tonic discharge of the MVN of the two sides during vestibular compensation, and for enhancing the dynamic responses of the deafferented MVN neurons in the long term.

Effects of glycolic acid on light-induced skin pigmentation in Asian and caucasian subjects.

PubMed

Tsai, T F; Bowman, P H; Jee, S H; Maibach, H I; Paul, B H

2000-08-01

Topical use of alpha-hydroxy acid (AHA) may increase skin photosensitivity, as demonstrated by increased numbers of sunburst cells. However, effects of AHA on tanning have not been studied. Our purpose was to study whether short-term use of glycolic acid hastens resolution of pre-existing light-induced pigmentation and whether the skin becomes tan more easily in Asian and Caucasian subjects after such treatment. Six Asian and six Caucasian volunteers received separate irradiations of UVB and UVA to both sides of the lower back. In a double-blind fashion, patients then applied a 10% glycolic acid gel, pH 3.52, to one side of the back, including the irradiated area, and the contralateral extensor forearms once daily for 7 days and then twice daily for 2 weeks. A placebo gel, pH 5.75, was applied to the opposite sides. The subjects returned for measurement of residual tanning with a colorimeter and received additional irradiation to forearms and a second site on the back. Resulting pigmentation was measured immediately after irradiation, at 2 hours, and at 1 week. Increased UVB-induced skin tanning occurred on the forearm and the lower back in both races in areas pretreated with glycolic acid. UVA also caused increased tanning, but only on the extensor forearms in Asian subjects. Treatment with glycolic acid for 3 weeks had no effect on pre-existing light-induced pigmentation. Short-term topical treatment of glycolic acid caused an increase in UVB tanning as well as in UVA tanning in some subjects, even in the absence of overt irritation. The inclusion of UVB, and even UVA, sunscreen in AHA products may be warranted.

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy

PubMed Central

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P.; Alexiou, Christoph; Janko, Christina

2017-01-01

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient’s body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications. PMID:28661430

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy.

PubMed

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P; Alexiou, Christoph; Janko, Christina

2017-06-29

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient's body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications.

Hydrostatic pressure enhances mitomycin C induced apoptosis in urothelial carcinoma cells.

PubMed

Chen, Shao-Kuan; Chung, Chih-Ang; Cheng, Yu-Che; Huang, Chi-Jung; Ruaan, Ruoh-Chyu; Chen, Wen-Yih; Li, Chuan; Tsao, Chia-Wen; Hu, Wei-Wen; Chien, Chih-Cheng

2014-01-01

Urothelial carcinoma (UC) of the bladder is the second most common cancer of the genitourinary system. Clinical UC treatment usually involves transurethral resection of the bladder tumor followed by adjuvant intravesical immunotherapy or chemotherapy to prevent recurrence. Intravesical chemotherapy induces fewer side effects than immunotherapy but is less effective at preventing tumor recurrence. Improvement to intravesical chemotherapy is, therefore, needed. Cellular effects of mitomycin C (MMC) and hydrostatic pressure on UC BFTC905 cells were assessed. The viability of the UC cells was determined using cellular proliferation assay. Changes in apoptotic function were evaluated by caspase 3/7 activities, expression of FasL, and loss of mitochondrial membrane potential. Reduced cell viability was associated with increasing hydrostatic pressure. Caspase 3/7 activities were increased following treatment of the UC cells with MMC or hydrostatic pressure. In combination with 10 kPa hydrostatic pressure, MMC treatment induced increasing FasL expression. The mitochondria of UC cells displayed increasingly impaired membrane potentials following a combined treatment with 10 μg/ml MMC and 10 kPa hydrostatic pressure. Both MMC and hydrostatic pressure can induce apoptosis in UC cells through an extrinsic pathway. Hydrostatic pressure specifically increases MMC-induced apoptosis and might minimize the side effects of the chemotherapy by reducing the concentration of the chemical agent. This study provides a new and alternative approach for treatment of patients with UC following transurethral resection of the bladder tumor. Copyright © 2014 Elsevier Inc. All rights reserved.

Oxaliplatin-induced blood brain barrier loosening: a new point of view on chemotherapy-induced neurotoxicity

PubMed Central

Valerio Branca, Jacopo Junio; Maresca, Mario; Morucci, Gabriele; Becatti, Matteo; Paternostro, Ferdinando; Gulisano, Massimo; Ghelardini, Carla; Salvemini, Daniela

2018-01-01

Oxaliplatin is a key drug in the treatment of advanced metastatic colorectal cancer. Despite its beneficial effects in tumor reduction, the most prevalent side-effect of oxaliplatin treatment is a chemotherapy-induced neuropathy that frequently forces to discontinue the therapy. Indeed, along with direct damage to peripheral nerves, the chemotherapy-related neurotoxicity involves also the central nervous system (CNS) as demonstrated by pain chronicity and cognitive impairment (also known as chemobrain), a newly described pharmacological side effect. The presence of the blood brain barrier (BBB) is instrumental in preventing the entry of the drug into the CNS; here we tested the hypothesis that oxaliplatin might enter the endothelial cells of the BBB vessels and trigger a signaling pathway that induce the disassembly of the tight junctions, the critical components of the BBB integrity. By using a rat brain endothelial cell line (RBE4) we investigated the signaling pathway that ensued the entry of oxaliplatin within the cell. We found that the administration of 10 μM oxaliplatin for 8 and 16 h induced alterations of the tight junction (TJs) proteins zonula occludens-1 (ZO-1) and of F-actin, thus highlighting BBB alteration. Furthermore, we reported that intracellular oxaliplatin rapidly induced increased levels of reactive oxygen species and endoplasmic reticulum stress, assessed by the evaluation of glucose-regulated protein GRP78 expression levels. These events were accompanied by activation of caspase-3 that led to extracellular ATP release. These findings suggested a possible novel mechanism of action for oxaliplatin toxicity that could explain, at least in part, the chemotherapy-related central effects.

Preventing Olanzapine-Induced Weight Gain Using Betahistine: A Study in a Rat Model with Chronic Olanzapine Treatment

PubMed Central

Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

2014-01-01

Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks) combination treatment of betahistine (an H1R agonist and H3R antagonist) and olanzapine (O+B) reduced (−45%) body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d.) and betahistine (9.6 mg/kg, t.i.d.) significantly reduced (−51.4%) weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP1 and PGC-1α protein levels in brown adipose tissue (BAT). The olanzapine induced changes in hypothalamic H1R, pAMPKα, BAT UCP1 and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment. PMID:25084453

N-acetylcysteine prevents stress-induced anxiety behavior in zebrafish.

PubMed

Mocelin, Ricieri; Herrmann, Ana P; Marcon, Matheus; Rambo, Cassiano L; Rohden, Aline; Bevilaqua, Fernanda; de Abreu, Murilo Sander; Zanatta, Leila; Elisabetsky, Elaine; Barcellos, Leonardo J G; Lara, Diogo R; Piato, Angelo L

2015-12-01

Despite the recent advances in understanding the pathophysiology of anxiety disorders, the pharmacological treatments currently available are limited in efficacy and induce serious side effects. A possible strategy to achieve clinical benefits is drug repurposing, i.e., discovery of novel applications for old drugs, bringing new treatment options to the market and to the patients who need them. N-acetylcysteine (NAC), a commonly used mucolytic and paracetamol antidote, has emerged as a promising molecule for the treatment of several neuropsychiatric disorders. The mechanism of action of this drug is complex, and involves modulation of antioxidant, inflammatory, neurotrophic and glutamate pathways. Here we evaluated the effects of NAC on behavioral parameters relevant to anxiety in zebrafish. NAC did not alter behavioral parameters in the novel tank test, prevented the anxiety-like behaviors induced by an acute stressor (net chasing), and increased the time zebrafish spent in the lit side in the light/dark test. These data may indicate that NAC presents an anti-stress effect, with the potential to prevent stress-induced psychiatric disorders such as anxiety and depression. The considerable homology between mammalian and zebrafish genomes invests the current data with translational validity for the further clinical trials needed to substantiate the use of NAC in anxiety disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of acupuncture at right Hoku point on the bilateral vibration-induced finger flexion reflex in man.

PubMed

Takakura, N; Kanamaru, A; Sibuya, M; Homma, I

1992-01-01

Vibration applied to the volar side of the finger tip has been reported to induce finger flexion reflex. Acupuncture is reported to inhibit this vibration-induced finger flexion reflex (VFR) in the ipsilateral hand. The purpose of this study was to investigate the effect of unilateral acupuncture in the hand on VFR in both hands. As no systematic study on the relationship between VFR and the force of voluntary contraction with no vibration (Initial Force: IF) has been reported, this relationship was studied prior to the present study on acupuncture. VFR was induced by mechanical vibration on the volar side of the middle finger tip with 10 g to 500 g IF. With approximately 300 g IF, VFR was consistent. Therefore, approximately 300 g IF was applied for VFR induction to study the effect of acupuncture on VFR. A stainless steel needle was inserted into the right Hoku point and remained inserted (in-situ technique) for 10 minutes. VFR in both hands was significantly decreased by acupuncture at the right Hoku point (% control force of VFR: right, 67.8%; left, 74.6%). The present results suggest that acupuncture in the unilateral hand influences the bilateral reflex arc of VFR.

Abnormal threshold voltage shift under hot carrier stress in Ti1-xNx/HfO2 p-channel metal-oxide-semiconductor field-effect transistors

NASA Astrophysics Data System (ADS)

Tsai, Jyun-Yu; Chang, Ting-Chang; Lo, Wen-Hung; Ho, Szu-Han; Chen, Ching-En; Chen, Hua-Mao; Tseng, Tseung-Yuen; Tai, Ya-Hsiang; Cheng, Osbert; Huang, Cheng-Tung

2013-09-01

This work investigates the channel hot carrier (CHC) effect in HfO2/Ti1-xNx p-channel metal oxide semiconductor field effect transistors (p-MOSFETs). Generally, the subthreshold swing (S.S.) should increase during CHC stress (CHCS), since interface states will be generated near the drain side under high electric field due to drain voltage (Vd). However, our experimental data indicate that S.S. has no evident change under CHCS, but threshold voltage (Vth) shifts positively. This result can be attributed to hot carrier injected into high-k dielectric near the drain side. Meanwhile, it is surprising that such Vth degradation is not observed in the saturation region during stress. Therefore, drain-induced-barrier-lowering (DIBL) as a result of CHC-induced electron trapping is proposed to explain the different Vth behaviors in the linear and saturation regions. Additionally, the influence of different nitrogen concentrations in HfO2/Ti1-xNx p-MOSFETs on CHCS is also investigated in this work. Since nitrogen diffuses to SiO2/Si interface induced pre-Nit occurring to degrades channel mobility during the annealing process, a device with more nitrogen shows slightly less impact ionization, leading to insignificant charge trapping-induced DIBL behavior.

Recommendations for the paracetamol treatment nomogram and side effects of N-acetylcysteine.

PubMed

Koppen, A; van Riel, A; de Vries, I; Meulenbelt, J

2014-06-01

Treatment of paracetamol intoxication consists of administration of N-acetylcysteine, preferably shortly after paracetamol ingestion. In most countries, the decision to treat patients with N-acetylcysteine depends on the paracetamol plasma concentration. In the literature, different arguments are given regarding when to treat paracetamol overdose. Some authors do not recommend treatment with N-acetylcysteine at low paracetamol plasma concentrations since unnecessary adverse effects may be induced. But no treatment with N-acetylcysteine at higher paracetamol plasma concentrations may lead to unnecessary severe morbidity and mortality. In this review, we provide an overview on the severity and prevalence of adverse side effects after N-acetylcysteine administration and the consequences these side effects may have for the treatment of paracetamol intoxication. The final conclusion is to continue using the guidelines of the Dutch National Poisons Information Centre for N-acetylcysteine administration in paracetamol intoxication.

Gravity-dependent regulation of red light induced moss protonemata branching and gametophore bud formation

NASA Astrophysics Data System (ADS)

Ripetskyj, R. T.; Kit, N. A.

Isolated leafy shoots of the moss Pottia intermedia positioned horizontally on the agar surface in vertically oriented petri dishes regenerate unbranching negatively gravitropic protonemata on upper side of the regenerant. Gravity determines the site of regeneration not the process itself. White light of low intensity unsufficient to induce positive phototropism of dark-grown protonemata can, however, provoke their branching and gametophore bud formation (Ripetskyj et al., 1998; 1999). The presented experiments have been carried out with red light in Biological Research in Canisters/Light Emitting Diode (BRIC/LED) hardware developed at Kennedy Space Center, USA. Seven-day-old dark-grown negatively gravitropic secondary P. intermedia protonemata were positioned differently with respect to gravity vector and to the source of red light of low, 1 or 2 μ mol\\cdot m-2\\cdot s-1, intensities. The light induced intensive branching of the protonemata and gametophore bud formation initiation site of both processes as well as the direction of growth of branches and buds being depent on the position of protonemata with respect to gravity and light vectors. Vertically positioned, i.e. ungravistimulated, dark grown protonemata illuminated from one side with red light of 2 μ mol\\cdot m-2\\cdot s-1 intensity produced 96,9 ± 2,2% of side branches and buds growing directly towards the light source from the lit protonema side. Horizontally disposed protonemata irradiated from below with red light of the same intensity regenerate 31,7 ± 3,9% of branches and buds on the upper, i.e. shaded protonemata side, the upward growth of which should undoubtedly be determined by gravity. In vertically disposed protonemata illuminated with red light of 1 μ mol\\cdot m-2\\cdot s-1 intensity from aside 31,9 ± 5,5% of side branches and buds arised on shaded protonema side and grew away from the light. Illumination of the protonemata in horizontal position from below increased the number of upgrowing branches and buds on upper shaded protonemata side to 76,9 ± 2,4%. The results convincingly speak for stimulating effect of the interaction of gravity and red light of low intensity. Characteristically, the number of side branches and buds on upper side of horizontally disposed protonemata illuminated from below (76,9 ± 2,4%) or parallely to protonemata length from their tips (86,0 ± 5,3%) were slightly, however, statistically significantly, greater than in the case of illumination from above (62,9 ± 3,1%). The effect may be probably be explained by some intensification of gravity action with red light of low intensity from shading of upper cell side or from lighting parallelly with respect to the cell surface. This research was supported by NASA grant NN-09(R).

Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls.

PubMed

Kontulainen, Saija; Sievänen, Harri; Kannus, Pekka; Pasanen, Matti; Vuori, Ilkka

2002-12-01

Bone characteristics of the humeral shaft and distal radius were measured from 64 female tennis and squash players and their 27 age-, height-, and weight-matched controls with peripheral quantitative tomography (pQCT) and DXA. The players were divided into two groups according to the starting age of their tennis or squash training (either before or after menarche) to examine the possible differences in the loading-induced changes in bone structure and volumetric density. The used pQCT variables were bone mineral content (BMC), total cross-sectional area (TotA) of bone, cross-sectional area of the marrow cavity (CavA) and that of the cortical bone (CoA), cortical wall thickness (CWT), volumetric density of the cortical bone (CoD) and trabecular bone (TrD), and torsional bone strength index (BSIt) for the shaft, and compressional bone strength index (BSIc) for the bone end. These bone strength indices were compared with the DXA-derived areal bone mineral density (aBMD) to assess how well the latter represents the effect of mechanical loading on apparent bone strength. At the humeral shaft, the loaded arm's greater BMC (an average 19% side-to-side difference in young starters and 9% in old starters) was caused by an enlarged cortex (CoA; side-to-side differences 20% and 9%, respectively). The loaded humerus seemed to have grown periosteally (the CavA did not differ between the sites) leading to 26% and 11% side-to-side BSIt difference in the young and old starters, respectively. CoD was equal between the arms (-1% difference in both player groups). The side-to-side differences in the young starters' BMC, CoA, TotA, CWT, and BSIt were 8-22% higher than those of the controls and 8-14% higher than those of the old starters. Old starters' BMC, CoA, and BSIt side-to-side differences were 6-7% greater than those in the controls. The DXA-derived side-to-side aBMD difference was 7% greater in young starters compared with that of the old starters and 14% compared with that in controls, whereas the difference between old starters and controls was 6%, in favor of the former. All these between-group differences were statistically significant. At the distal radius, the player groups differed significantly from controls in the side-to-side BMC, TrD, and aBMD differences only; the young starters' BMC difference was 9% greater, TrD and aBMD differences were 5% greater than those in the controls, and the old starters' TrD and aBMD differences were both 7% greater than those in the controls. In summary, in both of the female player groups the structural adaptation of the humeral shaft to long-term loading seemed to be achievedthrough periosteal enlargement of the bone cortex although this adaptation was clearly better in the young starters. Exercise-induced cortical enlargement was not so clear at the distal radius (a trabecular bone site), and the study suggested that at long bone ends also the TrD could be a modifiable factor to build a stronger bone structure. The conventional DXA-based aBMD measurement detected the intergroup differences in the exercise-induced bone gains, although, measuring two dimensions of bone only, it seemed to underestimate the effect of exercise on the apparent bone strength, especially if the playing had been started during the growing years.

Questionnaire about the adverse events and side effects following botulinum toxin A treatment in patients with cerebral palsy.

PubMed

Blaszczyk, Izabela; Foumani, Nazli Poorsafar; Ljungberg, Christina; Wiberg, Mikael

2015-11-06

Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report AEs is necessary to verify the safety of the treatment. We decided to use an active surveillance of treatment-induced harm using a questionnaire we created. We studied the incidence of reported AEs and side effects in patients with CP treated with BoNT-A. We investigated the relationship between the incidence of AEs or side effects and gender, age, weight, total dose, dose per body weight, Gross Motor Function Classification System (GMFCS) and number of treated body parts. Seventy-four patients with CP participated in our study. In 54 (51%) of 105 BoNT-A treatments performed in 45 (61%) patients, there were 95 AEs and side effects reported, out of which 50 were generalized and/or focal distant. Severe AEs occurred in three patients (4%), and their BoNT-A treatment was discontinued. Consecutive collection of the AE and side-effect incidence using our questionnaire can increase the safety of BoNT-A treatment in patients with CP.

Risperidone-Induced Renal Damage and Metabolic Side Effects: The Protective Effect of Resveratrol

PubMed Central

Korkmaz, Deniz Taştemir; Azirak, Sebile; Güvenç, Ayşe Nilay; Kocaman, Nevin

2017-01-01

Objective The aim of the study was to investigate the possible protective qualities of resveratrol (RSV) against the side effects of risperidone (RIS) in an experimental model in rat kidneys with histologic and biochemical assessments. Materials and Methods Experimental procedures were performed on 35 female Sprague Dawley rats. Rats were randomly divided into five groups: control, untreated rats (n = 7) were in group 1; group 2 was given 2 mg/kg/day RIS (n = 7); group 3 was treated with 2 mg/kg/day RIS and 20 mg/kg/day RSV (n = 7); group 4 was treated with 2 mg/kg/day RIS and 40 mg/kg/day RSV (n = 7); and group 5 was treated with 2 mg/kg/day RIS and 80 mg/kg/day RSV (n = 7). All treatments were administered for two weeks by gavage. On treatment day 15, kidney tissues were removed for analysis. Results The results showed that RSV treatment reduced weight gain induced by RIS. In addition, RSV increased the total antioxidant status (TAS) and decreased serum creatinine (Cr), blood urea nitrogen (BUN), oxidative stress index (OSI), and total oxidant status (TOS) levels significantly (p < 0.05). Conclusion This study revealed that treatment with RSV might protect kidney tissues against the side effects of RIS. RSV could be an effective course of therapy to enhance therapeutic efficacy. PMID:28706577

In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound healing effects and cytotoxicity/genotoxicity profile.

PubMed

Bagdas, Deniz; Etoz, Betul Cam; Gul, Zulfiye; Ziyanok, Sedef; Inan, Sevda; Turacozen, Ozge; Gul, Nihal Yasar; Topal, Ayse; Cinkilic, Nilufer; Tas, Sibel; Ozyigit, Musa Ozgur; Gurun, Mine Sibel

2015-07-01

Oxidative stress occurs following the impairment of pro-oxidant/antioxidant balance in chronic wounds and leads to harmful delays in healing progress. A fine balance between oxidative stress and endogenous antioxidant defense system may be beneficial for wound healing under redox control. This study tested the hypothesis that oxidative stress in wound area can be controlled with systemic antioxidant therapy and therefore wound healing can be accelerated. We used chlorogenic acid (CGA), a dietary antioxidant, in experimental diabetic wounds that are characterized by delayed healing. Additionally, we aimed to understand possible side effects of CGA on pivotal organs and bone marrow during therapy. Wounds were created on backs of streptozotocin-induced diabetic rats. CGA (50 mg/kg/day) was injected intraperitoneally. Animals were sacrificed on different days. Biochemical and histopathological examinations were performed. Side effects of chronic antioxidant treatment were tested. CGA accelerated wound healing, enhanced hydroxyproline content, decreased malondialdehyde/nitric oxide levels, elevated reduced-glutathione, and did not affect superoxide dismutase/catalase levels in wound bed. While CGA induced side effects such as cyto/genotoxicity, 15 days of treatment attenuated blood glucose levels. CGA decreased lipid peroxidation levels of main organs. This study provides a better understanding for antioxidant intake on diabetic wound repair and possible pro-oxidative effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of Korean Red Ginseng extract on busulfan-induced dysfunction of the male reproductive system.

PubMed

Jung, Seok-Won; Kim, Hyeon-Joong; Lee, Byung-Hwan; Choi, Sun-Hye; Kim, Hyun-Sook; Choi, Yang-Kyu; Kim, Joon Yong; Kim, Eun-Soo; Hwang, Sung-Hee; Lim, Kwang Yong; Kim, Hyoung-Chun; Jang, Minhee; Park, Seong Kyu; Cho, Ik-Hyun; Nah, Seung-Yeol

2015-07-01

Anticancer agents induce a variety of adverse effects when administered to cancer patients. Busulfan is a known antileukemia agent. When administered for treatment of leukemia in young patients, busulfan could cause damage to the male reproductive system as one of its adverse effects, resulting in sterility. We investigated the effects of Korean Red Ginseng extract (KRGE) on busulfan-induced damage and/or dysfunction of the male reproductive system. We found that administration of busulfan to mice: decreased testis weight; caused testicular histological damage; reduced the total number of sperm, sperm motility, serum testosterone concentration; and eventually, litter size. Preadministration of KRGE partially attenuated various busulfan-induced damages to the male reproductive system. These results indicate that KRGE has a protective effect against busulfan-induced damage to the male reproduction system. The present study shows a possibility that KRGE could be applied as a useful agent to prevent or protect the male reproductive system from the adverse side effects induced by administration of anticancer agents such as busulfan.

Reversal of olanzapine-induced weight gain in a patient with schizophrenia by switching to asenapine: a case report.

PubMed

Okazaki, Kosuke; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

2017-01-01

Antipsychotics are effective for treating schizophrenia, but atypical antipsychotics can cause several adverse side effects including weight gain, hyperprolactinemia, and extrapyramidal symptoms. Moreover, weight gain increases the risk of metabolic diseases. We treated a case of olanzapine-induced weight gain in a 41-year-old man with schizophrenia by switching his medication from olanzapine to asenapine. The weight gain improved after switching the medication, from 80.3 to 75.0 kg, a weight loss of 6.6%, and there was no significant worsening of psychological symptoms or other adverse effects. Asenapine might be effective for treating patients with schizophrenia who experience olanzapine-induced weight gain.

Mother root of Aconitum carmichaelii Debeaux exerts antinociceptive effect in Complet Freund's Adjuvant-induced mice: roles of dynorpin/kappa-opioid system and transient receptor potential vanilloid type-1 ion channel.

PubMed

Wang, Chao; Sun, Danni; Liu, Chunfang; Zhu, Chunyan; Jing, Xianghong; Chen, Shuping; Liu, Cuiling; Zhi, Kai; Xu, Tengfei; Wang, Hui; Liu, Junling; Xu, Ying; Liu, Zhiqiang; Lin, Na

2015-08-30

Processed Chuanwu (PCW), the mother root of Aconitum carmichaelii Debeauxv, has been widely used as a classic Traditional Chinese Medicine for pain relieve for over two millennia clinically. However, its action on chronic inflammatory pain has not been clarified. Here, we investigated the antinociceptive effect of PCW in complete freund's adjuvant (CFA)-induced mice and its possible mechanisms associated with opioid system and TRPV1 ion channel. Male ICR mice were intraplantarly injected with CFA. PCW (0.34, 0.68 and 1.35 g/kg) was orally given to mice once a day for 7 days. Von frey hairs and planter test were assessed to evaluate the antinociceptive effect of PCW. To investigate the participation of dynorphin/opioid system in PCW antinociception, subtype-specific opioid receptor antagonists or anti-dynorphin A antiserum were used. To eliminate other central mechanisms that contribute to PCW antinociception, hot plate (50 °C) test were performed. Further, involvements of TRPV1 in PCW antinociception were evaluated in CFA-induced TRPV1(-/-) and TRPV1(+/+) C57BL/6 male mice, and in capsaicin-induced nociception ICR naive mice pretreated with nor-BNI. Meanwhile, calcium imaging was performed in HEK293T-TRPV1 cells. Finally, rotarod, open-field tests and body temperature measurement were carried out to assess side effects of PCW. PCW dose-dependently attenuated mechanical and heat hypersensitivities with no tolerance, which could be partially attenuated by coadministration of k-opioid receptor antagonist nor-binaltorphimine (nor-BNI) or anti-dynorphin A (1-13) antiserum. And PCW antinociception was totally erased by pretreatment with nor-BNI in the hot plate test. In addition, PCW antinociception was decreased in TRPV1(-/-) mice compared to TRPV1(+/+) group. And PCW still manifested inhibitory effects in capsaicin-induced nociception with nor-BNI pretreatment. PCW significantly inhibited capsaicin-induced calcium influx in HEK293T-TRPV1 cells. Finally, no detectable side effects were found in naive mice treated with PCW. This study shows PCW's potent antinociceptive effect in inflammatory conditions without obvious side effects. This effect may result from the activation of κ-opioid receptor via dynorpin release and the inhibition of TRPV1. These findings indicate that PCW might be a potential agent for the management of chronic inflammatory pain.

Characterization of anti-inflammatory properties and evidence for no sedation liability for the novel antihistamine SUN-1334H.

PubMed

Mandhane, Sanjay N; Shah, Jigar H; Bahekar, Prashant C; Mehetre, Sameer V; Pawar, Chandrashekhar A; Bagad, Ashish S; Chidrewar, Gajanan U; Rao, Chitturi Trinadha; Rajamannar, Thennati

2010-01-01

The anti-inflammatory potential of antihistamines has significant clinical utility. Long-term pharmacotherapy of so-called 'safe' antihistamines may be hampered by side effects in the central nervous system. In the present study, the new potential antihistamine SUN-1334H was compared with different antihistamines for anti-inflammatory effects, sedation potential and interaction with alcohol. Nasal and skin allergy were induced in guinea pig and mice by ovalbumin sensitization and challenge. Neurogenic nasal inflammation was induced by capsaicin. Sedation potential and interaction with alcohol were assessed by i.v. and intracerebroventricular pentobarbital-induced sedation and alcohol-induced ataxia models. Ovalbumin sensitization and challenge caused rhinitis pathology including inflammatory cell infiltration, IL-4, and protein leakage in the nasal lavage fluid (NLF) and presence of inflammatory cells in nasal epithelium. A 5-day treatment of antihistamines reduced these markers of inflammation. SUN-1334H, cetirizine and hydroxyzine caused comparable inhibition of NLF leukocytes, IL-4 and total protein concentrations. Fexofenadine and desloratadine showed moderate inhibition of NLF leukocytes and had no significant effect on IL-4 concentration. While fexofenadine had no effect on total protein concentration, the effect of desloratadine was comparable with the other antihistamines. In neurogenic nasal inflammation induced by capsaicin, SUN-1334H and fexofenadine caused better inhibition at lower and middle dose levels than the other antihistamines. In skin allergy models, SUN-1334H showed potent reduction of passive and active cutaneous anaphylactic reactions. In central nervous system side effects models, SUN-1334H, desloratadine and fexofenadine were devoid of any significant effects. The results are suggestive of a high anti-inflammatory to sedation index of SUN-1334H among leading antihistamines.

Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats.

PubMed

Almeida, Jeferson; Duarte, Josiane O; Oliveira, Leandro A; Crestani, Carlos C

2015-01-01

Comorbidity between mood disorders and cardiovascular disease has been described extensively. However, available antidepressants can have cardiovascular side effects. Treatment with selective inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant effects, but whether the antidepressant-like effects of these drugs are followed by cardiovascular changes has not been previously investigated. Here, we tested in male rats exposed to chronic variable stress (CVS) the hypothesis that nNOS blockers are advantageous compared with conventional antidepressants in terms of cardiovascular side effects. We compared the effects of chronic treatment with the preferential nNOS inhibitor 7-nitroindazole (7-NI) with those evoked by the conventional antidepressant fluoxetine on alterations that are considered as markers of depression (immobility in the forced swimming test, FST, decreased body weight gain and increased plasma corticosterone concentration) and cardiovascular changes caused by CVS. Rats were exposed to a 14-day CVS protocol, while being concurrently treated daily with either 7-NI (30 mg/kg) or fluoxetine (10 mg/kg). Fluoxetine and 7-NI prevented the increase in immobility in the FST induced by CVS and reduced plasma corticosterone concentration in stressed rats. Both these treatments also prevented the CVS-evoked reduction of the depressor response to vasodilator agents and baroreflex changes. Fluoxetine and 7-NI-induced cardiovascular changes independent of stress exposure, including cardiac autonomic imbalance, increased intrinsic heart rate and vascular sympathetic modulation, a reduction of the pressor response to vasoconstrictor agents, and impairment of baroreflex activity. Altogether, these findings provide evidence that fluoxetine and 7-NI have similar effects on the depression-like state induced by CVS and on cardiovascular function.

[Drug-induced oral ulcerations].

PubMed

Madinier, I; Berry, N; Chichmanian, R M

2000-06-01

Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

Effects of calcaneal eversion on three-dimensional kinematics of the hip, pelvis and thorax in unilateral weight bearing.

PubMed

Tateuchi, Hiroshige; Wada, Osamu; Ichihashi, Noriaki

2011-06-01

Understanding the kinematic chain from foot to thorax will provide a better basis for assessment of malalignment of the body. The purpose of this study was to investigate the effects of induced calcaneal eversion on the kinematics of the hip, pelvis and thorax in three dimensions under unilateral weight-bearing. Twenty-eight healthy males were requested to stand on one leg under three conditions: normal (standing directly on the floor), and on wedges producing 5° and 10° calcaneal eversion. Recorded kinematic parameters included the angles of the hip joint, pelvis, and thorax in three dimensions. Eversion induced by wedges produced significant increases in hip flexion, hip medial rotation, pelvic anterior tilt, and thoracic lateral tilt and axial rotation to the standing side. In the frontal plane, pelvic lateral tilt to the standing side was decreased in 5° eversion condition compared with normal condition; conversely, it was increased in 10° eversion condition compared with 5° eversion condition. Arch height was negatively correlated with change in thoracic axial rotation to standing side from the normal to 10° eversion (r=-.528, p<.01). We concluded that induced calcaneal eversion affects the three-dimensional kinematics of the thorax through the hip joint and the pelvis. Copyright © 2011 Elsevier B.V. All rights reserved.

[The effect of drugs used in treatment of skin disorders on visual system].

PubMed

Szostakiewicz-Grabek, Beata; Juszkiewicz-Borowiec, Maria; Krasowska, Dorota

2016-04-01

Drugs with side effects affecting vision are often used in the treatment of skin disorders. The study evaluated principal groups of medicines which may negatively influence vision and the eye itself. Antimalaric drugs may cause a number of disorders of vision and a diagnosed retinophaty is an absolute contraindication. Retinoids often cause a dry eye condition, which results in intolerance to wearing contact lenses. They can also be a cause of poor nightly vision. Psoralens, used in photochemotherapy, can penetrate to the frontal part of the eye, inducing clouding of the lens and cataract. Glucocorticosteroids, often used in skin conditions, increase intraocular pressure, which may result in development of glaucoma. Methotrexate may also cause complications, such as eyelid edema, conjunctival hyperemia, increased lacrimation and photophobia. A prolonged use of tetracyclines may induce side effect in eye organs. Swelling of the optic nerve head with subsequent decreased vision, and even accumulate of metabolites of tetracycline within the conjunctival were observed. In the study a distinction was made between the medications which may lead to a temporary visual impairment and the medication with a side effect lasting beyond the treatment. It was pointed out that some of the side effects could be avoided or minimised by not combining retinoids and tetracyclines or with the use of protective eyewear during photochemotherapy. An examination by ophthalmologist is a crucial step prior to the treatment with chloroquine, hydroxychloroquine or psoralens. Regular eye exams are necessary when using, especially in a protracted fashion, most of the discussed drugs. Finally, the cooperation between dermatologist and ophthalmologist is fundamental for ensuring patient's safety. © 2016 MEDPRESS.

Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

PubMed

Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

2017-08-01

Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Electrostatics of lipid bilayer bending.

PubMed Central

Chou, T; Jarić, M V; Siggia, E D

1997-01-01

The electrostatic contribution to spontaneous membrane curvature is calculated within Poisson-Boltzmann theory under a variety of assumptions and emphasizing parameters in the physiological range. Asymmetrical surface charges can be fixed with respect to bilayer midplane area or with respect to the lipid-water area, but induce curvatures of opposite signs. Unequal screening layers on the two sides of a vesicle (e.g., multivalent cationic proteins on one side and monovalent salt on the other) also induce bending. For reasonable parameters, tubules formed by electrostatically induced bending can have radii in the 50-100-nm range, often seen in many intracellular organelles. Thus membrane associated proteins may induce curvature and subsequent budding, without themselves being intrinsically curved. Furthermore, we derive the previously unexplored effects of respecting the strict conservation of charge within the interior of a vesicle. The electrostatic component of the bending modulus is small under most of our conditions and is left as an experimental parameter. The large parameter space of conditions is surveyed in an array of graphs. Images FIGURE 1 FIGURE 10 PMID:9129807

Preventive Effect of Dihydromyricetin against Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo

PubMed Central

2016-01-01

Nephrotoxicity is a frequent severe side effect of cisplatin chemotherapy, limiting its clinical use despite being one of the most potent chemotherapy drugs. Dihydromyricetin is a highly abundant compound purified from the leaves of Ampelopsis grossedentata. Previous studies have demonstrated the anti-inflammatory and antioxidative effects of Dihydromyricetin both in vitro and in vivo, but little is known about the effects of Dihydromyricetin on cisplatin-induced nephrotoxicity and its underlying mechanisms. In the present study, we investigated its potential renoprotective effect and found that Dihydromyricetin ameliorated the renal functional impairment and structural damage caused by cisplatin. Moreover, Dihydromyricetin markedly attenuated cisplatin-induced oxidative stress, as well as protecting against cisplatin-induced inflammation and apoptotic cell death in mouse kidney tissues. These results collectively highlight the potential of DMY as a rational renoprotective agent against cisplatin. PMID:27642358

Focused Study on the Quiet Side Effect in Dwellings Highly Exposed to Road Traffic Noise

PubMed Central

Renterghem, Timothy Van; Botteldooren, Dick

2012-01-01

This study provides additional evidence for the positive effect of the presence of a quiet façade at a dwelling and aims at unraveling potential mechanisms. Locations with dominant road traffic noise and high Lden-levels at the most exposed façade were selected. Dwellings both with and without a quiet façade were deliberately sought out. Face-to-face questionnaires (N = 100) were taken to study the influence of the presence of a quiet side in relation to noise annoyance and sleep disturbance. As a direct effect, the absence of a quiet façade in the dwelling (approached as a front-back façade noise level difference smaller than 10 dBA) leads to an important increase of at least moderately annoyed people (odds-ratio adjusted for noise sensitivity equals 3.3). In an indirect way, a bedroom located at the quiet side leads to an even stronger reduction of the self-reported noise annoyance (odds-ratio equal to 10.6 when adjusted for noise sensitivity and front façade Lden). The quiet side effect seems to be especially applicable for noise sensitive persons. A bedroom located at the quiet side also reduces noise-induced sleep disturbances. On a loud side, bedroom windows are more often closed, however, conflicting with the preference of dwellers. PMID:23330222

Calcium channel blockers: spectrum of side effects and drug interactions.

PubMed

Hedner, T

1986-01-01

Calcium antagonists are a chemically heterogenous group of agents with potent cardiovascular effects which are beneficial in the treatment of angina pectoris, arterial hypertension and cardiac arrhythmias. The main side effects for the group are dose-dependent and the result of the main action or actions of the calcium antagonists, i.e. vasodilatation, negative inotropic effects and antiarrhythmic effects. Pronounced hypotension is reported for the main calcium antagonist drugs; verapamil, diltiazem and nifedipine. While conduction disturbances and bradycardia are seen more often after verapamil and diltiazem, tachycardia, headache and flush are more frequent after nifedipine. Constipation is relatively frequent after verapamil while nifedipine is reported to induce diarrhea in som patients. Idiosyncratic side effects are rare but have been reported from the skin, mouth, musculoskeletal system, the liver and the central nervous system. These side effects include urticarial rashes, gingival hyperplasia, arthralgia, hepathotoxicity and transistory mental confusion or akathisia. Verapamil, diltiazem and possibly also nifedipine have been reported to increase serum digoxin concentrations but the clinical relevance of these drug interactions are not clear. Furthermore, verapamil and diltiazem may potentiate the effects of beta-adrenergic blocking drugs and verapamil may also potentiate the effects of neuromuscular blocking drugs. It is concluded that side effects after calcium antagonist drugs are mostly trivial and transient although they may sometimes be relatively common. Clinically relevant drug interactions are few. Judged from the point of efficacy and safety, calcium antagonists will have a major place in the future pharmacotherapy of several cardiovascular disorders.

Chemical Modifications that Affect Nutritional and Functional Properties of Proteins.

ERIC Educational Resources Information Center

Richardson, T.; Kester, J. J.

1984-01-01

Discusses chemical alterations of selected amino acids resulting from environmental effects (photooxidations, pH extremes, thermally induced effects). Also dicusses use of intentional chemical derivatizations of various functional groups in amino acid residue side chains and how recombinant DNA techniques might be useful in structure/function…

Electrical characteristics of tunneling field-effect transistors with asymmetric channel thickness

NASA Astrophysics Data System (ADS)

Kim, Jungsik; Oh, Hyeongwan; Kim, Jiwon; Meyyappan, M.; Lee, Jeong-Soo

2017-02-01

Effects of using asymmetric channel thickness in tunneling field-effect transistors (TFET) are investigated in sub-50 nm channel regime using two-dimensional (2D) simulations. As the thickness of the source side becomes narrower in narrow-source wide-drain (NSWD) TFETs, the threshold voltage (V th) and the subthreshold swing (SS) decrease due to enhanced gate controllability of the source side. The narrow source thickness can make the band-to-band tunneling (BTBT) distance shorter and induce much higher electric field near the source junction at the on-state condition. In contrast, in a TFET with wide-source narrow-drain (WSND), the SS shows almost constant values and the V th slightly increases with narrowing thickness of the drain side. In addition, the ambipolar current can rapidly become larger with smaller thickness on the drain side because of the shorter BTBT distance and the higher electric-field at the drain junction. The on-current of the asymmetric channel TFET is lower than that of conventional TFETs due to the volume limitation of the NSWD TFET and high series resistance of the WSND TFET. The on-current is almost determined by the channel thickness of the source side.

Targeted drug induces responses in aggressive lymphomas

Cancer.gov

Preliminary results from clinical trials in a subtype of lymphoma show that for a number of patients whose disease was not cured by other treatments, the drug ibrutinib can provide significant anti-cancer responses with modest side effects.

Tonic cervical influences on eye nystagmus following hemilabyrinthectomy: immediate and plastic effects.

PubMed

Pettorossi, V E; Petrosini, L

1984-12-17

In intact guinea pigs a passive horizontal rotation of the body about the fixed head induces compensatory ocular movements (cervico-ocular reflex). When the static neck deviation is maintained, a significant ocular displacement is observed. In acutely hemilabyrinthectomized animals, static body deviation towards the lesion side tonically alters eye nystagmus. It affects slow phase eye velocity and quick phase amplitude and frequency causing the eye to reach a less eccentric orbital position. Apart from such immediate influences, a plastic effect on eye nystagmus abatement is induced. In the animals restrained with no body-on-head deviation, abatement of nystagmus is delayed with respect to the animals restrained with 35 degrees body deviation towards the lesion side. Thus the head position signal is not only a contributing factor for the correction of postural deficits but also influences the time course of the ocular balancing process following unilateral vestibular damage.

Objectively discriminating the optical analogy of electromagnetically induced transparency from Autler-Townes splitting in a side coupled graphene-based waveguide system

NASA Astrophysics Data System (ADS)

Wei, Buzheng; Jian, Shuisheng

2017-11-01

A mid-infrared side coupled graphene nanotube waveguide system is proposed to investigate the origin discerning from electromagnetically induced transparency (EIT) to Autler-Townes splitting (ATS). The analytic transmission analysis seeks an evolution tendency of transmission spectrum from ATS to EIT, which is numerically verified by the simulation results. The origin of transparency is mainly attributed to ATS effect in the strong coupling regime while EIT is favored in the weak coupling condition. We plot the field distribution to help understand the underlying physics of the interference process. The high group index of 5000 indicates that a slow light effect is successfully observed and Fano resonance is presented by varying the Fermi energy of the dark mode. These ideas may provide potential views in filters, optical buffers, light storage and on chip metamaterials.

Reversible metronidazole-induced neurotoxicity after 10 weeks of therapy.

PubMed

AlDhaleei, Wafa; AlMarzooqi, Ayesha; Gaber, Nouran

2018-04-20

Metronidazole is a commonly used antimicrobial worldwide. The most common side effects that have been reported are nausea, vomiting and hypersensitivity reactions. However, neurotoxicity has been reported with the use of metronidazole but rather rare. The most common neurological manifestation is peripheral neuropathy involvement in the form of sensory loss. It is worth mentioning that central neurotoxicity is a rare side effect of metronidazole use but reversible. The manifestations vary from a headache, altered mental status to focal neurological deficits. The diagnosis is mainly by neuroimaging in the setting of acute neurological change in the patient status. Here, we report a case of metronidazole-induced neurotoxicity in a 38-year-old male patient who was admitted with a brain abscess and was started on metronidazole for more than 10 weeks. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

EMP-induced BBB-disruption enhances drug delivery to glioma and increases treatment efficacy in rats.

PubMed

Li, Kangchu; Zhang, Keying; Xu, Shenglong; Wang, Xiaowu; Zhou, Yongchun; Zhou, Yan; Gao, Peng; Lin, Jiajin; Ding, Guirong; Guo, Guozhen

2018-01-01

Chemotherapy on gliomas is not satisfactorily efficient because the presence of blood-brain barriers (BBB) leads to inadequate exposure of tumor cells to administered drugs. In order to facilitate chemotherapeutics to penetrate BBB and increase the treatment efficacy of gliomas, electromagnetic pulse (EMP) was applied and the 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU) lomustine concentration in tumor tissue, tumor size, tumor apoptosis, and side effects were measured in glioma-bearing rat model. The results showed that EMP exposure could enhance the delivery of CCNU to tumor tissue, facilitate tumor apoptosis, and inhibit tumor growth without obvious side effects. The data indicated that EMP-induced BBB disruption could enhance delivery of CCNU to glioblastoma multiforme and increase treatment efficacy in glioma-bearing rats. Bioelectromagnetics. 39:60-67, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Acupuncture for Cancer-Induced Bone Pain?

PubMed Central

Paley, Carole A.; Bennett, Michael I.; Johnson, Mark I.

2011-01-01

Bone pain is the most common type of pain in cancer. Bony metastases are common in advanced cancers, particularly in multiple myeloma, breast, prostate or lung cancer. Current pain-relieving strategies include the use of opioid-based analgesia, bisphosphonates and radiotherapy. Although patients experience some pain relief, these interventions may produce unacceptable side-effects which inevitably affect the quality of life. Acupuncture may represent a potentially valuable adjunct to existing strategies for pain relief and it is known to be relatively free of harmful side-effects. Although acupuncture is used in palliative care settings for all types of cancer pain the evidence-base is sparse and inconclusive and there is very little evidence to show its effectiveness in relieving cancer-induced bone pain (CIBP). The aim of this critical review is to consider the known physiological effects of acupuncture and discuss these in the context of the pathophysiology of malignant bone pain. The aim of future research should be to produce an effective protocol for treating CIBP with acupuncture based on a sound, evidence-based rationale. The physiological mechanisms presented in this review suggest that this is a realistic objective. PMID:21799687

Cardiac ion channels

PubMed Central

Priest, Birgit T; McDermott, Jeff S

2015-01-01

Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

Optokinetic motion sickness - Attenuation of visually-induced apparent self-rotation by passive head movements

NASA Technical Reports Server (NTRS)

Teixeira, R. A.; Lackner, J. R.

1979-01-01

An experimental study was conducted on seven normal subjects to evaluate the effectiveness of passive head movements in suppressing the optokinetically-induced illusory self-rotation. Visual simulation was provided by a servo-controlled optokinetic drum. Each subject participated in two experimental sessions. In one condition, the subject's head remained stationary while he gazed passively at a moving stripe pattern. In the other, he gazed passively and relaxed his neck muscles while his head was rotated from side to side. It appears that suppression of optokinetically-induced illusory self-rotation with passive head movements results from the operation of a spatial constancy mechanism interrelating visual, vestibular, and kinesthetic information on ongoing body orientation. The results support the view that optokinetic 'motion sickness' is related, at least in part, to an oculomotor disturbance rather than a visually triggered disturbance of specifically vestibular etiology.

Long-Term Drainage from the Riprap Side Slope of a Surface Barrier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Zhuanfang

Surface barriers designed to isolate underground nuclear waste in place are expected to function for at least 1000 years. To achieve this long design life, such barriers need to be protected with side slopes against wind- and water-induced erosion and damage by natural or human activities. However, the side slopes are usually constructed with materials coarser than the barrier. Their hydrological characteristics must be understood so that any drainage from them is considered in the barrier design and will not compromise the barrier function. The Prototype Hanford Barrier, an evapotranspiration-capillary (ETC) barrier, was constructed in 1994 at the Hanford Sitemore » in southeastern Washington state, with a gravel side slope and a riprap side slope. The soil water content in the gravel side slope and drainage from both side slopes have been monitored since the completion of construction. The monitoring results show that under natural precipitation the annual drainage rates from the two types of side slopes were very similar and about 5 times the typical recharge from local soil with natural vegetation and 40 times the barrier design criterion. The higher recharge from the side slopes results in some of the drainage migrating laterally to the region beneath the ETC barrier. This edge effect of the enhanced drainage was evaluated for a period of 1000 years by numerical simulation. The edge effect was quantified by the amount of water across the barrier edges and the affecting distance of the barrier edges. These results indicate that design features can be adjusted to reduce the edge effect when necessary.« less

Disorder-induced transparency in a one-dimensional waveguide side coupled with optical cavities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yongyou, E-mail: yyzhang@bit.edu.cn; Dong, Guangda; Zou, Bingsuo

2014-05-07

Disorder influence on photon transmission behavior is theoretically studied in a one-dimensional waveguide side coupled with a series of optical cavities. For this sake, we propose a concept of disorder-induced transparency appearing on the low-transmission spectral background. Two kinds of disorders, namely, disorders of optical cavity eigenfrequencies and relative phases in the waveguide side coupled with optical cavities are considered to show the disorder-induced transparency. They both can induce the optical transmission peaks on the low-transmission backgrounds. The statistical mean value of the transmission also increases with increasing the disorders of the cavity eigenfrequencies and relative phases.

Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release?

PubMed

Bijlsma, Elisabeth Y; Chan, Johnny S W; Olivier, Berend; Veening, Jan G; Millan, Mark J; Waldinger, Marcel D; Oosting, Ronald S

2014-06-01

Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. © 2013 Elsevier Inc. All rights reserved.

Fs-laser-induced Ca2+ concentration change during membrane perforation for cell transfection.

PubMed

Baumgart, J; Bintig, W; Ngezahayo, A; Lubatschowski, H; Heisterkamp, A

2010-02-01

Fs-laser based opto-perforation is a gentle method for gene transfer into sensitive cells such as stem cells or primary cells. The high selectivity and the low damage to the cell lead to a high efficiency of transfection. However, there are side effects which induce stress to the cell due to the exchange of intra- and extracellular media as well as the disintegration of the structure of biomolecules resulting from the laser exposure. Moreover, the mechanisms of the optical transfection are still unclear. In this paper, we present our study on calcium (Ca(2+)) homeostasis during cell surgery, especially during laser induced membrane perforation. We show that the manipulation of cells can induce an increase in the cytosolic Ca(2+) concentration. This increase was not observed if the manipulation of the cells was performed in absence of the extracellular calcium indicating the importance of the Ca(2+) uptake. We found, that the uptake of extracellular Ca(2+) strongly depends on the repetition rate and the irradiation time of the laser pulses. The exposure for several seconds to kHz pulses even induces Ca(2+) induced Ca(2+) release. Dependent on the location of perforation, probably in the vicinity of an intracellular Ca(2+) stock, an instantaneous intracellular Ca(2+) release can be induced. Since Ca(2+) could be involved in negative side effect by cell surgery, we propose an application of the optoperforation technique in nominal Ca(2+)-free external solution.

Optical cell cleaning with NIR femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Uchugonova, Aisada; Breunig, Hans Georg; Batista, Ana; König, Karsten

2015-03-01

Femtosecond laser microscopes have been used as both micro and nanosurgery tools. The optical knock-out of undesired cells in multiplex cell clusters shall be further reported on in this study. Femtosecond laser-induced cell death is beneficial due to the reduced collateral side effects and therefore can be used to selectively destroy target cells within monolayers, as well as within 3D tissues, all the while preserving cells of interest. This is an important characteristic for the application in stem cell research and cancer treatment. Non-precise damage compromises the viability of neighboring cells by inducing side effects such as stress to the cells surrounding the target due to the changes in the microenvironment, resulting from both the laser and laser-exposed cells. In this study, optimum laser parameters for optical cleaning by isolating single cells and cell colonies are exploited through the use of automated software control. Physiological equilibrium and cellular responses to the laser induced damages are also investigated. Cell death dependence on laser focus, determination and selectivity of intensity/dosage, controllable damage and cell recovery mechanisms are discussed.

Osteonecrosis of the jaw - prevention and treatment strategies for oral health professionals.

PubMed

Hinchy, Nicole V; Jayaprakash, Vijayvel; Rossitto, Rachael A; Anders, Patrick L; Korff, Kathryn C; Canallatos, Paul; Sullivan, Maureen A

2013-09-01

Patients diagnosed with multiple myeloma and metastatic breast, prostate and renal cancers have a better opportunity for longer survival due to a myriad of chemotherapies regimens that attempt to manage disease progression while decreasing treatment-related side effects. Osteonecrosis of the jaws (ONJ) is a known side effect of bisphosphonates and other anti-neoplastic drugs. This complication can lead to oncologic treatment interruptions as well as diminished quality of life. Most recommendations for treatment of ONJ are based on position papers and case reports, while evidence-based treatment paradigms are lacking. With cancer survivorship on the rise, long-term chemotherapeutic side effects are becoming more prevalent and attention to untoward oral complications cannot be understated. In this review, the accepted recommendations for dental clearance prior to head and neck chemo-radiation therapy are put forth as a means of possibly preventing and treating drug induced ONJ. Copyright © 2013 Elsevier Ltd. All rights reserved.

Autoradiographic and biochemical observations on the distribution of non-steroid anti-inflammatory drugs.

PubMed

Rainsford, K D; Schweitzer, A; Brune, K

1981-04-01

A comparison has been made of the distribution of some new radioactively-labelled non-steroid anti-inflammatory (NSAI) drugs or pro-drugs with their respective progenitors and/or standard acidic NSAI drugs (i.e. aspirin, indomethacin and phenylbutazone), using whole body autoradiography and scintillation counting. The object of this study was to establish if the distribution of these new NSAI drugs may contribute to changes in their side-, or therapeutic effects compared with the older drugs. All the NSAI drugs accumulated in those tissues wherein the principle therapeutic and side-effects are manifest. The accumulation in inflamed tissues occurs regardless of the structural type of NSAI drugs, i.e. with specific accumulation occurring in this tissue of the acidic drugs or their acidic metabolites. New aspects of the distribution of the acetyl moiety of aspirin are reported which may be significant in relation to the side-effects induced by this drug.

Benzocaine-Induced Methemoglobinemia

PubMed Central

Sachdeva, Rajesh; Pugeda, Jaime G.; Casale, Linda R.; Meizlish, Jay L.; Zarich, Stuart W.

2003-01-01

We describe the cases of 2 patients who developed benzocaine-induced methemoglobinemia after the administration of benzocaine as premedication for transesophageal echocardiography. The use of intravenous methylene blue resolved the cyanosis in both patients. Physicians who perform procedures involving the application of topical anes thesia need to be aware of this side effect to prevent morbidity and mortality. (Tex Heart Inst J 2003;30:308–10) PMID:14677742

Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy

PubMed Central

Das, Bidyut Kumar

2011-01-01

Azithromycin is a widely used macrolide derivative and has generally been considered to be a very safe medication. Though gastrointestinal symptoms and reversible hearing loss are common, potentially serious side effects including angioedema and cholestatic jaundice occurred in less than one percent of patients. We report a case of asymptomatic dilated cardiomyopathy with Azithromycin induced severe hepatocellular toxicity and hepatic encephalopathy. PMID:22144789

Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy.

PubMed

Gheorghe, Liana; Cotruta, Bogdan; Trifu, Viorel; Cotruta, Cristina; Becheanu, Gabriel; Gheorghe, Cristian

2008-09-01

Pegylated interferon-alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweet's syndrome in association with pegylated interferon-alpha therapy.

Efavirenz-induced gynecomastia in a prepubertal girl with human immunodeficiency virus infection: a case report

PubMed Central

2013-01-01

Background Prepubertal gynecomastia is a rare condition and most frequently classified as idiopathic. In HIV-infected adults gynecomastia is a recognised but infrequent side-effect of antiretroviral treatment (ART) and mostly attributed to efavirenz use. Gynecomastia should be distinguished from pseudogynecomastia as part of the lipodystrophy syndrome caused by Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to avoid incorrect substitution of drugs. In the medical literature only five cases of prepubertal gynecomastia in children taking ART are described and underlying pathogenesis was unknown. The occurrence of adverse effects of ART may interfere with therapy adherence and long-term prognosis and for that reason requires attention. We report the first case of prepubertal gynecomastia in a young girl attributed to efavirenz use. Case presentation A seven-year-old African girl presented with true gynecomastia four months after initiation on ART (abacavir, lamivudine, efavirenz). History, physical examination and laboratory tests excluded known causes of gynecomastia and efavirenz was considered as the most likely cause. Six weeks after withdrawal of efavirenz the breast enlargement had completely resolved. Conclusions Efavirenz-induced gynecomastia may occur in children as well as in adults. With the increasing access to ART, the possibility of efavirenz-exposure and the potential occurrence of its associated side-effects may be high. In resource-poor settings, empirical change from efavirenz to nevirapine may be considered, providing no other known or alarming cause is identified, as efavirenz-induced gynecomastia can resolve quickly after withdrawal of the drug. Timely recognition of gynecomastia as a side-effect of efavirenz is important in order to intervene while the condition may still be reversible, to sustain adherence to ART and to maintain the sociopsychological health of the child. PMID:23941256

Efavirenz-induced gynecomastia in a prepubertal girl with human immunodeficiency virus infection: a case report.

PubMed

van Ramshorst, Mette S; Kekana, Magdeline; Struthers, Helen E; McIntyre, James A; Peters, Remco P H

2013-08-13

Prepubertal gynecomastia is a rare condition and most frequently classified as idiopathic. In HIV-infected adults gynecomastia is a recognised but infrequent side-effect of antiretroviral treatment (ART) and mostly attributed to efavirenz use. Gynecomastia should be distinguished from pseudogynecomastia as part of the lipodystrophy syndrome caused by Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to avoid incorrect substitution of drugs. In the medical literature only five cases of prepubertal gynecomastia in children taking ART are described and underlying pathogenesis was unknown. The occurrence of adverse effects of ART may interfere with therapy adherence and long-term prognosis and for that reason requires attention. We report the first case of prepubertal gynecomastia in a young girl attributed to efavirenz use. A seven-year-old African girl presented with true gynecomastia four months after initiation on ART (abacavir, lamivudine, efavirenz). History, physical examination and laboratory tests excluded known causes of gynecomastia and efavirenz was considered as the most likely cause. Six weeks after withdrawal of efavirenz the breast enlargement had completely resolved. Efavirenz-induced gynecomastia may occur in children as well as in adults. With the increasing access to ART, the possibility of efavirenz-exposure and the potential occurrence of its associated side-effects may be high. In resource-poor settings, empirical change from efavirenz to nevirapine may be considered, providing no other known or alarming cause is identified, as efavirenz-induced gynecomastia can resolve quickly after withdrawal of the drug. Timely recognition of gynecomastia as a side-effect of efavirenz is important in order to intervene while the condition may still be reversible, to sustain adherence to ART and to maintain the sociopsychological health of the child.

Glucocorticoid (dexamethasone)-induced metabolome changes in healthy males suggest prediction of response and side effects.

PubMed

Bordag, Natalie; Klie, Sebastian; Jürchott, Kathrin; Vierheller, Janine; Schiewe, Hajo; Albrecht, Valerie; Tonn, Jörg-Christian; Schwartz, Christoph; Schichor, Christian; Selbig, Joachim

2015-11-03

Glucocorticoids are indispensable anti-inflammatory and decongestant drugs with high prevalence of use at (~)0.9% of the adult population. Better holistic insights into glucocorticoid-induced changes are crucial for effective use as concurrent medication and management of adverse effects. The profiles of 214 metabolites from plasma of 20 male healthy volunteers were recorded prior to and after ingestion of a single dose of 4 mg dexamethasone (+20 mg pantoprazole). Samples were drawn at three predefined time points per day: seven untreated (day 1 midday - day 3 midday) and four treated (day 3 evening - day 4 evening) per volunteer. Statistical analysis revealed tremendous impact of dexamethasone on the metabolome with 150 of 214 metabolites being significantly deregulated on at least one time point after treatment (ANOVA, Benjamini-Hochberg corrected, q < 0.05). Inter-person variability was high and remained uninfluenced by treatment. The clearly visible circadian rhythm prior to treatment was almost completely suppressed and deregulated by dexamethasone. The results draw a holistic picture of the severe metabolic deregulation induced by single-dose, short-term glucocorticoid application. The observed metabolic changes suggest a potential for early detection of severe side effects, raising hope for personalized early countermeasures increasing quality of life and reducing health care costs.

The Potential Benefit of Radiotherapy with Protons in Head and Neck Cancer with Respect to Normal Tissue Sparing: A Systematic Review of Literature

PubMed Central

Bijl, Hendrik P.; Schilstra, Cornelis; Pijls-Johannesma, Madelon; Langendijk, Johannes A.

2011-01-01

Purpose. Clinical studies concerning head and neck cancer patients treated with protons reporting on radiation-induced side effects are scarce. Therefore, we reviewed the literature regarding the potential benefits of protons compared with the currently used photons in terms of lower doses to normal tissue and the potential for fewer subsequent radiation-induced side effects, with the main focus on in silico planning comparative (ISPC) studies. Materials and Methods. A literature search was performed by two independent researchers on ISPC studies that included proton-based and photon-based irradiation techniques. Results. Initially, 877 papers were retrieved and 14 relevant and eligible ISPC studies were identified and included in this review. Four studies included paranasal sinus cancer cases, three included nasopharyngeal cancer cases, and seven included oropharyngeal, hypopharyngeal, and/or laryngeal cancer cases. Seven studies compared the most sophisticated photon and proton techniques: intensity-modulated photon therapy versus intensity-modulated proton therapy (IMPT). Four studies compared different proton techniques. All studies showed that protons had a lower normal tissue dose, while keeping similar or better target coverage. Two studies found that these lower doses theoretically translated into a significantly lower incidence of salivary dysfunction. Conclusion. The results of ISPC studies indicate that protons have the potential for a significantly lower normal tissue dose, while keeping similar or better target coverage. Scanned IMPT probably offers the most advantage and will allow for a substantially lower probability of radiation-induced side effects. The results of these ISPC studies should be confirmed in properly designed clinical trials. PMID:21349950

Polymorphism of μ-Opioid Receptor Gene (OPRM1:c.118A>G) Might Not Protect against or Enhance Morphine-Induced Nausea or Vomiting

PubMed Central

Chen, Li-Kuei; Chen, Shiou-Sheng; Huang, Chi-Hsiang; Yang, Hong-Jyh; Lin, Chen-Jung; Chien, Kuo-Liong; Fan, Shou-Zen

2013-01-01

A cohort, double blind, and randomized study was conducted to investigate the effect of a single nucleotide polymorphism of the μ-opioid receptor at nucleotide position 118 (OPRM1:c.118A>G) on the association with the most common side effects (nausea or vomiting) induced by intravenous patient control analgesia (IVPCA) with morphine, including incidence and severity analysis. A total of 129 Taiwanese women undergoing gynecology surgery received IVPCA with pure morphine for postoperative pain relief. Blood samples were collected and sequenced with high resolution melting analysis to detect three different genotypes of OPRM1 (AA, AG, and GG). All candidates 24 h postoperatively will be interviewed to record the clinical phenotype with subjective complaints and objective observations. The genotyping after laboratory analysis showed that 56 women (43.4%) were AA, 57 (44.2%) were AG, and 16 (12.4%) were GG. The distribution of genotype did not violate Hardy-Weinberg equilibrium test. There was no significant difference neither between the severity and incidence of IVPCA morphine-induced side effects and genotype nor between the association between morphine consumption versus genotype. However, there was significant difference of the relation between morphine consumption and the severity and incidence of IVPCA morphine-induced nausea and vomiting. The genetic analysis for the severity and incidence of IVPCA morphine-induced nausea or vomiting showed no association between phenotype and genotype. It might imply that OPRM1:c.118A>G does not protect against IVPCA morphine-induced nausea or vomiting. PMID:23431434

Delicaflavone induces autophagic cell death in lung cancer via Akt/mTOR/p70S6K signaling pathway.

PubMed

Sui, Yuxia; Yao, Hong; Li, Shaoguang; Jin, Long; Shi, Peiying; Li, Zhijun; Wang, Gang; Lin, Shilan; Wu, Youjia; Li, Yuxiang; Huang, Liying; Liu, Qicai; Lin, Xinhua

2017-03-01

Searching for potential anticancer agents from natural sources is an effective strategy for developing novel chemotherapeutic agents. In this study, data supporting the in vitro and in vivo anticancer effects of delicaflavone, a rarely occurring biflavonoid from Selaginella doederleinii, were reported. Delicaflavone exhibited favorable anticancer properties, as shown by the MTT assay and xenograft model of human non-small cell lung cancer in male BALB/c nude mice without observable adverse effect. By transmission electron microscopy with acridine orange and Cyto-ID®Autophagy detection dyes, Western blot analysis, and RT-PCR assay, we confirmed that delicaflavone induces autophagic cell death by increasing the ratio of LC3-II to LC3-I, which are autophagy-related proteins, and promoting the generation of acidic vesicular organelles and autolysosomes in the cytoplasm of human lung cancer A549 and PC-9 cells in a time- and dose-dependent manner. Delicaflavone downregulated the expression of phospho-Akt, phospho-mTOR, and phospho-p70S6K in a time- and dose-dependent manner, suggesting that it induced autophagy by inhibiting the Akt/mTOR/p70S6K pathway in A549 and PC-9 cells. Delicaflavone is a potential anticancer agent that can induce autophagic cell death in human non-small cell lung cancer via the Akt/mTOR/p70S6K signaling pathway. Delicaflavone showed anti-lung cancer effects in vitro and in vivo. Delicaflavone induced autophagic cell death via Akt/mTOR/p70S6K signaling pathway. Delicaflavone did not show observable side effects in a xenograft mouse model. Delicaflavone may represent a potential therapeutic agent for lung cancer. Delicaflavone showed anti-lung cancer effects in vitro and in vivo. Delicaflavone induced autophagic cell death via Akt/mTOR/p70S6K signaling pathway. Delicaflavone did not show observable side effects in a xenograft mouse model. Delicaflavone may represent a potential therapeutic agent for lung cancer.

The impact of traffic-flow patterns on air quality in urban street canyons.

PubMed

Thaker, Prashant; Gokhale, Sharad

2016-01-01

We investigated the effect of different urban traffic-flow patterns on pollutant dispersion in different winds in a real asymmetric street canyon. Free-flow traffic causes more turbulence in the canyon facilitating more dispersion and a reduction in pedestrian level concentration. The comparison of with and without a vehicle-induced-turbulence revealed that when winds were perpendicular, the free-flow traffic reduced the concentration by 73% on the windward side with a minor increase of 17% on the leeward side, whereas for parallel winds, it reduced the concentration by 51% and 29%. The congested-flow traffic increased the concentrations on the leeward side by 47% when winds were perpendicular posing a higher risk to health, whereas reduced it by 17-42% for parallel winds. The urban air quality and public health can, therefore, be improved by improving the traffic-flow patterns in street canyons as vehicle-induced turbulence has been shown to contribute significantly to dispersion. Copyright © 2015 Elsevier Ltd. All rights reserved.

Co-production of GroELS discriminates between intrinsic and thermally-induced recombinant protein aggregation during substrate quality control

PubMed Central

2011-01-01

Background The effects and effectiveness of the chaperone pair GroELS on the yield and quality of recombinant polypeptides produced in Escherichia coli are matter of controversy, as the reported activities of this complex are not always consistent and eventually indicate undesired side effects. The divergence in the reported data could be due, at least partially, to different experimental conditions in independent research approaches. Results We have then selected two structurally different model proteins (namely GFP and E. coli β-galactosidase) and two derived aggregation-prone fusions to explore, in a systematic way, the eventual effects of GroELS co-production on yield, solubility and conformational quality. Host cells were cultured at two alternative temperatures below the threshold at which thermal stress is expected to be triggered, to minimize the involvement of independent stress factors. Conclusions From the analysis of protein yield, solubility and biological activity of the four model proteins produced alone or along the chaperones, we conclude that GroELS impacts on yield and quality of aggregation-prone proteins with intrinsic determinants but not on thermally induced protein aggregation. No effective modifications of protein solubility have been observed, but significant stabilization of small (encapsulable) substrates and moderate chaperone-induced degradation of larger (excluded) polypeptides. These findings indicate that the activities of this chaperone pair in the context of actively producing recombinant bacteria discriminate between intrinsic and thermally-induced protein aggregation, and that the side effects of GroELS overproduction might be determined by substrate size. PMID:21992454

Two models for weight gain and hyperphagia as side effects of atypical antipsychotics in male rats: validation with olanzapine and ziprasidone.

PubMed

Shobo, Miwako; Yamada, Hiroshi; Mihara, Takuma; Kondo, Yuji; Irie, Megumi; Harada, Katsuya; Ni, Keni; Matsuoka, Nobuya; Kayama, Yukihiko

2011-01-20

Body weight gain is one of the most serious side effects associated with clinical use of antipsychotics. However, the mechanisms by which antipsychotics induce body weight gain are unknown, and no reliable animal models of antipsychotics-induced weight gain have been established. The present studies were designed to establish male rat models of weight gain induced by chronic and acute treatment with antipsychotics. Six-week chronic treatment with olanzapine (5, 7.5, and 10mg/kg/day) in male Sprague-Dawley rats fed a daily diet resembling a human macronutrient diet, significantly increased body weight gain and weight of fatty tissues. In contrast, ziprasidone (1.25, 2.5, and 5mg/kg/day) administration caused no observable adverse effects. We then investigated feeding behavior with acute antipsychotic treatment in male rats using an automated food measurement apparatus. Rats were allowed restricted access to normal laboratory chow (4h/day). With acute olanzapine (0.5, 1, and 2mg/kg, i.p.) treatment in the light phase, food intake volume and duration were significantly increased, while treatment with ziprasidone (0.3, 1, and 3mg/kg, i.p.) did not increase food intake volume or meal time duration. Findings from the present studies showed that chronic treatment with olanzapine in male rats induced body weight gain, and acute injection induced hyperphagia, suggesting that hyperphagia may be involved in the weight gain and obesity-inducing properties of chronically administered olanzapine. These animal models may provide useful experimental platforms for analysis of the mechanism of hyperphagia and evaluating the potential risk of novel antipsychotics to induce weight gain in humans. Copyright © 2010 Elsevier B.V. All rights reserved.

Subsonic aerodynamic characteristics of interacting lifting surfaces with separated flow around sharp edges predicted by a vortex-lattice method

NASA Technical Reports Server (NTRS)

Lamar, J. E.; Gloss, B. B.

1975-01-01

Because the potential flow suction along the leading and side edges of a planform can be used to determine both leading- and side-edge vortex lift, the present investigation was undertaken to apply the vortex-lattice method to computing side-edge suction force for isolated or interacting planforms. Although there is a small effect of bound vortex sweep on the computation of the side-edge suction force, the results obtained for a number of different isolated planforms produced acceptable agreement with results obtained from a method employing continuous induced-velocity distributions. By using the method outlined, better agreement between theory and experiment was noted for a wing in the presence of a canard than was previously obtained.

BGP-15 Protects against Oxaliplatin-Induced Skeletal Myopathy and Mitochondrial Reactive Oxygen Species Production in Mice.

PubMed

Sorensen, James C; Petersen, Aaron C; Timpani, Cara A; Campelj, Dean G; Cook, Jordan; Trewin, Adam J; Stojanovska, Vanesa; Stewart, Mathew; Hayes, Alan; Rybalka, Emma

2017-01-01

Chemotherapy is a leading intervention against cancer. Albeit highly effective, chemotherapy has a multitude of deleterious side-effects including skeletal muscle wasting and fatigue, which considerably reduces patient quality of life and survivability. As such, a defense against chemotherapy-induced skeletal muscle dysfunction is required. Here we investigate the effects of oxaliplatin (OXA) treatment in mice on the skeletal muscle and mitochondria, and the capacity for the Poly ADP-ribose polymerase (PARP) inhibitor, BGP-15, to ameliorate any pathological side-effects induced by OXA. To do so, we investigated the effects of 2 weeks of OXA (3 mg/kg) treatment with and without BGP-15 (15 mg/kg). OXA induced a 15% ( p < 0.05) reduction in lean tissue mass without significant changes in food consumption or energy expenditure. OXA treatment also altered the muscle architecture, increasing collagen deposition, neutral lipid and Ca 2+ accumulation; all of which were ameliorated with BGP-15 adjunct therapy. Here, we are the first to show that OXA penetrates the mitochondria, and, as a possible consequence of this, increases mtROS production. These data correspond with reduced diameter of isolated FDB fibers and shift in the fiber size distribution frequency of TA to the left. There was a tendency for reduction in intramuscular protein content, albeit apparently not via Murf1 (atrophy)- or p62 (autophagy)- dependent pathways. BGP-15 adjunct therapy protected against increased ROS production and improved mitochondrial viability 4-fold and preserved fiber diameter and number. Our study highlights BGP-15 as a potential adjunct therapy to address chemotherapy-induced skeletal muscle and mitochondrial pathology.

Antidepressant effects, of magnetic seizure therapy and electroconvulsive therapy, in treatment-resistant depression.

PubMed

Kayser, Sarah; Bewernick, Bettina H; Grubert, Christiane; Hadrysiewicz, Barbara L; Axmacher, Nikolai; Schlaepfer, Thomas E

2011-05-01

Major depression is a common mental health problem and associated with significant morbidity and mortality, including impaired social and physical functioning and increased risk for suicide. Electroconvulsive therapy (ECT) is highly efficacious in treatment-resistant depressive disorders, but cognitive side effects are frequently associated with the treatment. Magnetic seizure therapy (MST) is a form of convulsive therapy, using magnetic fields in order to induce therapeutic seizures. First studies suggested that cognitive side effects of MST, including postictal recovery time, are more benign than those resulting from ECT treatment. In this open-label study we tested the hypothesis that MST is associated with clinically significant antidepressant effects in treatment-resistant depression (TRD) as an add-on therapy to a controlled pharmacotherapy. Twenty patients suffering from TRD were randomly assigned to receive either MST or ECT starting from July 2006 until November 2008. Primary outcome measure was antidepressant response assessed by Montgomery Åsberg Depression Scale. Secondary outcome measures included Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Beck Depression Inventory and 90-Item Symptom Checklist. Antidepressant response (improvement of 50% in MADRS ratings) was statistically significant and of similar size in both treatment groups. Cognitive side effects were observed in neither group. Characteristics in MST- and ECT-induced seizures were comparable, especially regarding ictal activity and postictal suppression. Thus, MST may be a potential alternative to ECT if efficacy and safety are validated in larger clinical trials. Copyright © 2010 Elsevier Ltd. All rights reserved.

Pregnenolone blocks cannabinoid-induced acute psychotic-like states in mice

PubMed Central

Busquets-Garcia, Arnau; Soria-Gómez, Edgar; Redon, Bastien; Mackenbach, Yarmo; Chaouloff, Francis; Varilh, Marjorie; Ferreira, Guillaume; Piazza, Pier-Vincenzo; Marsicano, Giovanni

2017-01-01

Cannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood. The use of antipsychotics and benzodiazepines against CIAPS is limited by side-effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed. Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy. The neurosteroid pregnenolone has been recently shown to act as a potent endogenous allosteric signal-specific inhibitor of CB1 receptors. Thus, we tested in mice the potential therapeutic use of pregnenolone against acute psychotic-like effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. We found that pregnenolone blocks a wide spectrum of THC-induced endophenotypes typically associated with psychotic-like states, including impairments in cognitive functions, somatosensory gating and social interaction. In order to capture THC-induced positive psychotic-like symptoms (e.g. perceptual delusions), we adapted a behavioral paradigm based on associations between different sensory modalities and selective devaluation, allowing the measurement of mental sensory representations in mice. Acting at hippocampal CB1 receptors, THC impaired the correct processing of mental sensory representations (reality testing) in an antipsychotic- and pregnenolone-sensitive manner. Overall, this work reveals that signal-specific inhibitors mimicking pregnenolone effects can be considered as promising new therapeutic tools to treat CIAPS. PMID:28220044

The small-molecule TNF-alpha modulator, UTL-5g, reduces side effects induced by cisplatin and enhances the therapeutic effect of cisplatin in vivo.

PubMed

Shaw, JiaJiu; Chen, Ben; Huang, Wen-Hsin; Lee, An-Rong; Media, Joseph; Valeriote, Frederick A

2011-01-01

We investigated a small-molecule modulator of tumor necrosis factor alpha (TNF-alpha), UTL-5g (also referred to as GBL-5g), as a potential chemoprotective agent against cisplatin-induced side effects including nephrotoxicity, hepatotoxicity and hematotoxicity. Pretreatment of UTL-5g i.p. in BDF1 mice reduced the levels of blood urea nitrogen (BUN) and creatinine induced by cisplatin treatment. The levels of both aspartate transaminase (AST) and alanine transaminase (ALT) in these animals were also reduced by UTL-5g. Pretreatment of UTL-5g did not significantly affect the number of white blood cells (WBC) under current experimental conditions, yet it markedly increased blood platelet counts by more than threefold. Therapeutic assessment in SCID mice inoculated with human HCT-15 tumor cells showed that UTL-5g did not attenuate the anti-tumor effect of cisplatin but increased the therapeutic efficacy of cisplatin. The LD50 of UTL-5g was determined to be > 2,000 mg/kg by an acute toxicity study. In summary, our studies showed that 1) UTL-5g significantly reduces nephrotoxicity and hepatotoxicity induced by cisplatin in mice, presumably by lowering the levels of TNF-alpha, 2) UTL-5g markedly increased blood platelet counts in mice and 3) UTL-5g treatment increased the therapeutic efficacy of cisplatin against HCT-15 cells inoculated in SCID mice.

Counseling the Client with Prostate Cancer.

ERIC Educational Resources Information Center

Curtis, Russell C.; Juhnke, Gerald A.

2003-01-01

Prostate cancer is prevalent in the United States and has a far-reaching effect on men and their relationships. Being diagnosed with and treated for prostate cancer often causes men to experience side effects that induce physical, emotional, and social change. Counselors need to be aware of prostate cancer's impact on men and their families.…

Kerato-lenticular ocular deposits and visual impairment with prolonged chlorpromazine use: A case series.

PubMed

Gowda, Guru S; Hegde, Aditya; Shanbhag, Vandita; Narayanaswamy, Janardhanan C; Jaisoorya, T S

2017-02-01

Chlorpromazine is a low potency "typical" antipsychotic agent used to treat schizophrenia. It continues to be prescribed frequently in India owing to its lower cost. There have been previous reports of ocular adverse effects with prolonged use of chlorpromazine. We report three patients who developed corneal and lenticular opacities secondary to prolonged chlorpromazine use leading to visual impairment. Early detection of ocular deposits and switching over to risperidone from chlorpromazine helped in the reversal of chlorpromazine- induced ocular side effects in one of them. The case series further adds evidence to the causative relationship between chlorpromazine and ocular side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

PPARγ partial agonist GQ-16 strongly represses a subset of genes in 3T3-L1 adipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milton, Flora Aparecida; Genomic Medicine, Houston Methodist Research Institute, Houston, TX; Cvoro, Aleksandra

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists that improve insulin resistance but trigger side effects such as weight gain, edema, congestive heart failure and bone loss. GQ-16 is a PPARγ partial agonist that improves glucose tolerance and insulin sensitivity in mouse models of obesity and diabetes without inducing weight gain or edema. It is not clear whether GQ-16 acts as a partial agonist at all PPARγ target genes, or whether it displays gene-selective actions. To determine how GQ-16 influences PPARγ activity on a gene by gene basis, we compared effects of rosiglitazone (Rosi) and GQ-16 in mature 3T3-L1more » adipocytes using microarray and qRT-PCR. Rosi changed expression of 1156 genes in 3T3-L1, but GQ-16 only changed 89 genes. GQ-16 generally showed weak effects upon Rosi induced genes, consistent with partial agonist actions, but a subset of modestly Rosi induced and strongly repressed genes displayed disproportionately strong GQ-16 responses. PPARγ partial agonists MLR24 and SR1664 also exhibit disproportionately strong effects on transcriptional repression. We conclude that GQ-16 displays a continuum of weak partial agonist effects but efficiently represses some negatively regulated PPARγ responsive genes. Strong repressive effects could contribute to physiologic actions of GQ-16. - Highlights: • GQ-16 is an insulin sensitizing PPARγ ligand with reduced harmful side effects. • GQ-16 displays a continuum of weak partial agonist activities at PPARγ-induced genes. • GQ-16 exerts strong repressive effects at a subset of genes. • These inhibitor actions should be evaluated in models of adipose tissue inflammation.« less

Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells.

PubMed

Choi, Byung-Min; Chen, Xiao Yan; Gao, Shang Shang; Zhu, Rizhe; Kim, Bok-Ryang

2011-01-01

Cisplatin is a highly effective chemotherapeutic agent, but it has significant ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell loss following exposure to cisplatin. The present study examined the effects of phloretin, a natural polyphenolic compound found in apples and pears, on cisplatin-induced apoptosis. We found that phloretin induced the expression of heme oxygenase-1 (HO-1) protein in a concentration- and time-dependent manner. Phloretin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation, and dominant-negative Nrf2 attenuated phloretin-induced expression of HO-1. Phloretin activated the JNK, ERK and p38 mitogen-activated protein kinase (MAPK) pathways, and the JNK pathway played an important role in phloretin-induced HO-1 expression. Phloretin protected the cells against cisplatin-induced apoptosis. The protective effect of phloretin was abrogated by zinc protoporphyrin IX (ZnPP IX), a HO inhibitor. Furthermore, phloretin pretreatment inhibited mitochondrial dysfunction and the activation of caspases. These results demonstrate that the expression of HO-1 induced by phloretin is mediated by both the JNK pathway and Nrf2; the expression inhibits cisplatin-induced apoptosis in HEI-OC1 cells.

Factors affecting drug-induced liver injury: antithyroid drugs as instances

PubMed Central

Niknahad, Hossein; Jamshidzadeh, Akram; Abdoli, Narges

2014-01-01

Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed. PMID:25320726

Aripiprazole-induced sleep-related eating disorder: a case report.

PubMed

Kobayashi, Nobuyuki; Takano, Masahiro

2018-04-05

Sleep-related eating disorder is characterized by parasomnia with recurrent episodes of nocturnal eating or drinking during the main sleep period. Several drugs, including atypical antipsychotics, induce sleep-related eating disorder. However, aripiprazole has not previously been associated with sleep-related eating disorder. A 41-year-old Japanese man visited our clinic complaining of depression. The patient was treated with sertraline, which was titrated up to 100 mg for 4 weeks. A sleep inducer and an anxiolytic were coadministered. His depressive mood slightly improved, but it continued for an additional 4 months. Subsequently, aripiprazole (3 mg) was added as an adjunctive therapy. After 3 weeks, the patient's mother found that the patient woke up and ate food at night. The next morning, the patient was amnesic for this event, felt full, and wondered why the bags of food were empty. This episode lasted for 2 days. The patient gained 5 kg during these 3 weeks. After the aripiprazole dose was reduced to 1.5 mg, the patient's nocturnal eating episodes rapidly and completely disappeared. To the best of our knowledge, this is first report of sleep-related eating disorder induced by aripiprazole, and it indicates that this disorder should be considered a possible side effect of aripiprazole. Although aripiprazole is used mainly in patients with schizophrenia, its recently documented use as an adjunctive therapy in patients with depression might induce hitherto unknown side effects.

Enhancing the Effects of Low Dose Doxorubicin Treatment by the Radiation in T47D and SKBR3 Breast Cancer Cells

PubMed Central

Aghaee, Fahimeh; Baradaran, Behzad; Mesbahi, Asghar; Mohammadzadeh, Mohammad; Jafarabadi, Mohammad Asghari

2013-01-01

Purpose Breast cancer is the most common malignancy of women worldwide. Radiotherapy consists of a vital element in the treatment of breast cancer but relative side effects and different radioactive responses are limiting factors for a successful treatment. Doxorubicin has been used to treat cancers for over 30 years and is considered as the most effective drug in the treatment of breast cancer. There are also many chronic side effects that limit the amount of doxorubicin that can be administered. The combined radio-drug treatment, with low doses, can be an approach for reducing side effects from single modality treatments instead of suitable cure rates. Methods We have studied the effect of 1, 1.5, and 2 Gy doses of 9 MV X-rays along with 1 µM doxorubicin on inducing cell death, apoptosis and also p53 and PTEN gene expression in T47D and SKBR3 breast cancer cells. Results Doxorubicin treatment resulted in upregulation of radiation-induced levels of p53 and downregulation of PTEN at 1 and 1.5 Gy in T47D breast cancer cells, as well as downregulation of p53 mRNA level of expression and upregulation of PTEN mRNA level of expression in SKBR3 breast cancer cell line. In addition, doxorubicin in combination with radiation decreased the viability of breast cancer cell lines in the both cell lines. Conclusion Low doses of doxorubicin, with least cell toxicity, may be an effective treatment for breast cancer when used in conjunction with ionizing radiation. PMID:23843848

Anti-tumor and Chemoprotective Effect of Bauhinia tomentosa by Regulating Growth Factors and Inflammatory Mediators.

PubMed

Kannan, Narayanan; Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

2015-01-01

Cancer is a leading cause of death worldwide. Due to the toxic side effects of the commonly used chemotherapeutic drug cyclophosphamide (CTX), the use of herbal medicines with fewer side effects but having potential use as inducing anti-cancer outcomes in situ has become increasingly popular. The present study sought to investigate the effects of a methanolic extract of Bauhinia tomentosa against Dalton's ascites lymphoma (DAL) induced ascites as well as solid tumors in BALB/c mice. Specifically, B. tomentosa extract was administered intraperitonealy (IP) at 10 mg/kg. BW body weight starting just after tumor cell implantation and thereafter for 10 consecutive days. In the ascites tumor model hosts, administration of extract resulted in a 52% increase in the life span. In solid tumor models, co-administration of extract and CTX significantly reduced tumor volume (relative to in untreated hosts) by 73% compared to just by 52% when the extract alone was provided. Co-administration of the extract also mitigated CTX-induced toxicity, including decreases in WBC count, and in bone marrow cellularity and α-esterase activity. Extract treatment also attenuated any increases in serum levels of TNFα, iNOS, IL-1β, IL-6, GM-CSF, and VEGF seen in tumor-bearing hosts. This study confirmed that, the potent antitumor activity of B.tomentosa extract may be associated with immune modulatory effects by regulating anti-oxidants and cytokine levels.

Haloperidol-induced changes in glutathione and energy metabolism: effect of nicergoline.

PubMed

Vairetti, M; Feletti, F; Battaglia, A; Pamparana, F; Canonico, P L; Richelmi, P; Bertè, F

1999-02-12

The aim of this study was to evaluate the possible effects of nicergoline, a semisynthetic ergot derivative, on the biochemical changes observed during chronic treatment with haloperidol in male Sprague-Dawley rats. Chronic treatment with haloperidol induced a significant decrease in the cellular glutathione (GSH) content in selected areas of the brain (cerebellum, striatum and cortex) and in the liver. Prolonged nicergoline administration was able to antagonize the haloperidol-induced GSH decrease, maintaining the GSH concentration at levels comparable to those observed in the control group. Analysis of the energy charge revealed changes similar to those observed for GSH: haloperidol induced a significant decrease in ATP and energy charge that was completely reversed by repeated nicergoline administration. In conclusion, chronic treatment with the classical antipsychotic haloperidol induces profound biochemical changes in the brain and in the liver. Nicergoline treatment is able to counteract the haloperidol-induced decrease in GSH levels and energy charge, suggesting a potential role of the drug in the treatment of neuroleptic-induced side effects.

Effect of molecular asymmetry on the charge transport physics of high mobility n-type molecular semiconductors investigated by scanning Kelvin probe microscopy.

PubMed

Hu, Yuanyuan; Berdunov, Nikolai; Di, Chong-an; Nandhakumar, Iris; Zhang, Fengjiao; Gao, Xike; Zhu, Daoben; Sirringhaus, Henning

2014-07-22

We have investigated the influence of the symmetry of the side chain substituents in high-mobility, solution processable n-type molecular semiconductors on the performance of organic field-effect transistors (OFETs). We compare two molecules with the same conjugated core, but either symmetric or asymmetric side chain substituents, and investigate the transport properties and thin film growth mode using scanning Kelvin probe microscopy (SKPM) and atomic force microscopy (AFM). We find that asymmetric side chains can induce a favorable two-dimensional growth mode with a bilayer structure, which enables ultrathin films with a single bilayer to exhibit excellent transport properties, while the symmetric molecules adopt an unfavorable three-dimensional growth mode in which transport in the first monolayer at the interface is severely hindered by high-resistance grain boundaries.

Cognitive side-effects of electroconvulsive therapy in elderly depressed patients.

PubMed

Dybedal, Gro Strømnes; Tanum, Lars; Sundet, Kjetil; Gaarden, Torfinn Lødøen; Bjølseth, Tor Magne

2014-01-01

Knowledge about cognitive side-effects induced by electroconvulsive therapy (ECT) in depressed elderly patients is sparse. In this study we investigated changes in the cognitive functioning of non-demented elderly depressed patients receiving ECT (n = 62) compared with healthy elderly people (n = 17). Neuropsychological tests were administered at the start of treatment and again within 1 week after treatment. We computed reliable change indices (RCIs) using simple regression methods. RCIs are statistical methods for analyzing change in individuals that have not yet been used in studies of the acute cognitive side-effects of ECT. At the group level, only letter fluency performance was found to be significantly reduced in the ECT group compared with the controls, whereas both groups demonstrated stable or improved performance on all other measures. At the individual level, however, 11% of patients showed retrograde amnesia for public facts post-ECT and 40% of the patients showed a significant decline in neuropsychological functioning. Decline on a measure of delayed verbal anterograde memory was most common. Our findings indicate that there are mild neurocognitive impairments in the acute phase for a substantial minority of elderly patients receiving ECT. Analysis of reliable change facilitated the illumination of cognitive side-effects in our sample.

An update on analgesics.

PubMed

Power, I

2011-07-01

Recent introduction of new analgesics into the clinic is best described as a slow process with activity classified into two main areas: improving analgesic efficacy/potency and reducing side-effect profile. This review article describes some of the recent advances with an emphasis on use in the acute setting. In this respect, opioids continue to be the mainstay (but not the only) analgesic and there have been important improvements in their clinical effect profile. For example, tapentadol has been introduced as a mixed opioid and norepinephrine uptake inhibitor which, unlike tramadol, does not require metabolic activation and does not suffer from isomer-dependent pharmacodynamics. Opioid antagonists have received much attention recently either used alone, methylnaltrexone (s.c) or alvimopan (p.o), or in combination, Targinact (oxycodone/naloxone), and appear to be effective in reducing opioid side-effects such as those in the gastrointestinal tract. Other agents where there has been recent development include the use of gabapentin, methylxanthines, and local anaesthetics. An interesting area of translation of basic research is in the inhibition of breakdown of endogenous opioids with opiorphin, targeting of the endocannabinoid system, and the use of ampakines to obtund opioid-induced side-effects. It is clear that there is still much work to be done, but the need for highly efficacious analgesics with good side-effect profile remains.

Postnatal Experience Modulates Functional Properties of Mouse Olfactory Sensory Neurons

PubMed Central

He, Jiwei; Tian, Huikai; Lee, Anderson C.; Ma, Minghong

2012-01-01

Early experience considerably modulates the organization and function of all sensory systems. In the mammalian olfactory system, deprivation of the sensory inputs via neonatal, unilateral naris closure has been shown to induce structural, molecular, and functional changes from the olfactory epithelium to the olfactory bulb and cortex. However, it remains unknown how early experience shapes functional properties of individual olfactory sensory neurons (OSNs), the primary odor detectors in the nose. To address this question, we examined odorant response properties of mouse OSNs in both the closed and open nostril after four weeks of unilateral naris closure with age-matched untreated animals as control. Using patch-clamp technique on genetically-tagged OSNs with defined odorant receptors (ORs), we found that sensory deprivation increased the sensitivity of MOR23 neurons in the closed side while overexposure caused the opposite effect in the open side. We next analyzed the response properties including rise time, decay time, and adaptation induced by repeated stimulation in MOR23 and M71 neurons. Even though these two types of neurons showed distinct properties in dynamic range and response kinetics, sensory deprivation significantly slowed down the decay phase of odorant-induced transduction events in both types. Using western blotting and antibody staining, we confirmed upregulation of several signaling proteins in the closed side as compared with the open side. This study suggests that early experience modulates functional properties of OSNs, probably via modifying the signal transduction cascade. PMID:22703547

Ranitidine-induced black tongue: A case report.

PubMed

Akcaboy, Meltem; Sahin, Sanliay; Zorlu, Pelin; Şenel, Saliha

2017-11-01

Black tongue is a rare, benign, self-limiting disorder caused by certain conditions and some medications. We report the first case of a child diagnosed with black tongue associated with ranitidine use. We report our case to emphasize the rare side effect of this frequently used drug. Health care professionals should be aware of the likelihood of ranitidine-induced black tongue in clinical practice. © 2017 Wiley Periodicals, Inc.

Aripiprazole-Induced Hypoprolactinemia in an Adult Male with First-Episode Psychosis.

PubMed

Propst, Alanna J; Jarvis, G Eric; Margolese, Howard C

2016-01-01

Aripiprazole is an atypical antipsychotic that acts as a partial agonist at dopamine D2 receptors. Compared to other atypical antipsychotics, aripiprazole has less metabolic side effects and is less likely to increase prolactin. Moreover, it has been shown to have a unique prolactin lowering effect. While aripiprazole has been associated with subnormal prolactin levels in children, no documented cases of hypoprolactinemia in adults exist thus far. Here we report a case of aripiprazole-induced hypoprolactinemia in an adult male with first-episode psychosis, and the possible effects of abnormally low prolactin are discussed.

Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats.

PubMed

Li, Min; Wang, Ke; Su, Wen-Ting; Jia, Jun; Wang, Xiao-Min

2017-10-06

To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model. Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance. Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007). EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.

Vincristine-induced blindness: a case report and review of literature.

PubMed

Adhikari, Subodh; Dongol, Raj Man; Hewett, Yvonne; Shah, Binay Kumar

2014-11-01

Neurotoxicity is a dose-limiting side-effect of vincristine therapy. Blindness is a rare central neurotoxicity of vincristine with few case reports. In the present article, we report a rare case of vincristine-induced blindness in a patient with diffuse large B cell lymphoma. Literature search identified eleven published cases of vincristine-induced blindness. We reviewed patient characteristics, chemotherapy used and type of blindness. Vincristine-induced blindness is rare and unpredictable. Prompt recognition and discontinuation of vincristine may lead to recovery of vision. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Localized periorbital edema induced by Ibuprofen.

PubMed

Palungwachira, Piti; Palungwachira, Pranee; Ogawa, Hideoki

2005-12-01

We documented localized periorbital edema in one patient with ibuprofen sensitivity without underlying chronic urticaria. The reaction developed one hour after ingestion of 200 mg of ibuprofen. No systemic symptoms were observed. No other NSAIDs did not induce symptoms. This patient was able to tolerate doses of ibuprofen after pretreatment with terfenadine. These observations suggest that histamine played a central role in this ibuprofen-induced skin reaction. Treatment with terfenadine enabled the patient to tolerate ibuprofen without experiencing any side effects. To the best of our knowledge, this is the first reported case of periorbital edema induced by ibuprofen.

Calcitonin-gene related peptide is a potent inducer of oedema in rat orofacial tissue.

PubMed

Queiroz, Bárbara F G de; Almeida, Marcella P A de; Bakhle, Y S; Francischi, Janetti N

2018-04-01

This study aimed to assess the potential of calcitonin-gene related peptide (CGRP), a neuropeptide released from sensory nerves, to induce oedema in orofacial tissue. Wistar rats (150-200 g) anesthetized with isoflurane were injected intraorally with CGRP (100 μl; 8-33 pmol) in the right side of the mouth. The contralateral side was injected with the same volume of physiological saline. Increased cheek thickness (in mm), as a measure of oedema formation, was assayed bilaterally with a digital caliper before (T = 0) and up to 24 h following injection of CGRP. Pretreatment with antagonists (CGRP 8-37, 10 nmol; pizotifen, 2 mg/kg) was given by intra-oral or subcutaneous injection, 10 or 30 min, respectively, before the inflammatory stimulus. CGRP and CGRP 8-37 were also injected into the rat hind paw to induce oedema. Data are presented as the mean (±SEM) difference in thickness between the right and the left sides at each time. Following intra-oral injection, CGRP induced a rapidly developing (5-15 min) and long-lasting (6 h), dose-dependent oedema in the rat cheek, blocked by pre-treatment with CGRP 8-37 or pizotifen. CGRP induced a smaller oedematogenic effect in the rat hind paw also blocked by the CGRP antagonist. CGRP (16 pmol) potentiated the oedema induced by co-injected substance P (3.7 nmol) and contributed to the oedema following intraoral injection of carrageenan (100 μg). Injection of CGRP 8-37 alone induced an early but short-lasting oedema. Local injection of CGRP potently induced oedema in the orofacial tissue of rats which was blocked by a CGRP receptor antagonist. The overall inhibition of carrageenan-induced oedema by CGRP 8-37 suggests that endogenous CGRP contributes to an oedematogenic response in orofacial tissues. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hair loss at injection sites of mesotherapy for alopecia.

PubMed

El-Komy, Mohamed; Hassan, Akmal; Tawdy, Amira; Solimon, Mohamed; Hady, Mohamed Abdel

2017-12-01

The side effects of mesotherapy for treatment of various forms of alopecia are often underreported, while scientific data for its efficacy are severely lacking. To demonstrate the late onset side effects of mesotherapy for alopecia. Three patients with androgenetic alopecia showed hair loss after previously uneventful mesotherapy sessions up to 1 year. Clinical, dermoscopic, and histopathological findings suggested an inflammatory scaring process at sites of mesotherapy injections. Mesotherapy for androgenetic alopecia may paradoxically induce hair loss and scarring. Proper regulation and monitoring of the use of mesotherapy products for treating hair loss in women, needs to be addressed. © 2017 Wiley Periodicals, Inc.

Relapsed hydroxychloroquine induced thrombocytopenia in a systemic lupus erythematosus patient.

PubMed

Antón Vázquez, Vanesa; Pascual, Luis; Corominas, Héctor; Giménez Torrecilla, Isabel

Hydroxychloroquine is used in the long-term therapy of systemic lupus erythematosus (SLE). Although considered to be a safe treatment, side effects have been documented. An uncommon side effect is thrombocytopenia. In order to establish the diagnosis of thrombocytopenia secondary to Hydroxychloroquine, non-pharmacological causes must be ruled out and it is necessary to determine a recurrence after re-exposure to the drug. We present one case of severe thrombocytopenia occurring in a patient with SLE undergoing treatment with Hydroxychloroquine. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Liver immunology and herbal treatment

PubMed Central

Balaban, Yasemin H; Aka, Ceylan; Koca-Caliskan, Ufuk

2017-01-01

Beyond the metabolic functions, the liver recently has been defined as an organ of immune system (IS), which have central regulatory role for innate and adaptive immunity. The liver keeps a delicate balance between hepatic screening of pathogenic antigens and immune tolerance to self-antigens. Herbal treatments with immunological effects have potential to alter this hepatic immune balance towards either therapeutic side or diseases side by inducing liver injury via hepatotoxicity or initiation of autoimmune diseases. Most commonly known herbal treatments, which have therapeutic effect on liver and IS, have proven via in vitro, in vivo, and/or clinical studies were summarized in this review. PMID:28660010

A review and assessment of drug-induced parotitis.

PubMed

Brooks, Krista G; Thompson, Dennis F

2012-12-01

To review the current literature on drug-induced parotitis. Literature was accessed through MEDLINE/PubMed (1980-May 2012), using the search terms sialadenitis/chemically induced and parotitis/chemically induced. EMBASE (1980-May 2012) was searched using the terms parotitis/diagnosis, sialadenitis/side effect, and parotitis/side effect. International Pharmaceutical Abstracts (1970-May 2012) was searched using the search terms parotitis and sialadenitis. All searches were limited to articles on humans written in English. Inclusion criteria were published letters, case reports, reviews, and clinical trials involving drugs that may be associated with parotitis. Articles pertaining to parotitis induced by iodine-containing drugs were excluded. References of all relevant articles were reviewed for additional citations. Review articles, clinical trials, background data, and case reports of drug-induced parotitis were collected and case reports were assessed for causality. Parotitis is an uncommon adverse effect; however, signs and symptoms of parotitis have been noted in case reports as an adverse drug reaction related to various medications. Assessing causality of an adverse drug reaction such as parotitis is challenging. To help determine the probability of causality for these events, algorithms such as the Naranjo probability scale have been developed. Eighty-four case reports of drug-induced parotitis from 40 different drugs were reviewed using a modified Naranjo probability scale that included criteria specific for parotitis. Medications that met the criteria for establishing causality included l-asparaginase with 7 case reports, clozapine with 13 case reports, and phenylbutazone with 13 case reports. Drug-induced parotitis is a rare adverse drug reaction. Based on the quantitative and qualitative evidence collected from the case reports, medications that are associated with drug-induced parotitis include l-asparaginase, clozapine, and phenylbutazone. Many other drugs have been implicated in the development of parotitis; however, the evidence supporting this association is insufficient to determine causality at this time.

Attenuation of cryocooler induced vibration using multimodal tuned dynamic absorber

NASA Astrophysics Data System (ADS)

Veprik, A.; Babitsky, V.; Tuito, A.

2017-12-01

Modern infrared imagers often rely on low Size, Weight and Power split Stirling linear cryocoolers comprised of side-by-side packed compressor and expander units fixedly mounted upon a common frame and interconnected by the configurable transfer line. Imbalanced reciprocation of moving assemblies generates vibration export in the form of tonal force couple producing angular and translational dynamic responses. Resulting line of sight jitter and dynamic defocusing may affect the image quality. The authors explore the concept of multimodal tuned dynamic absorber, the translational and tilting modal frequencies of which are essentially matched to the driving frequency. Dynamic analysis and full-scale testing show that the dynamic reactions (forces and moments) produced by such a device may effectively attenuate both translational and angular components of cryocooler-induced vibration.

High temperature-induced abnormal suppression of sub-threshold swing and on-current degradations under hot-carrier stress in a-InGaZnO thin film transistors

NASA Astrophysics Data System (ADS)

Tsai, Ming-Yen; Chang, Ting-Chang; Chu, Ann-Kuo; Hsieh, Tien-Yu; Chen, Te-Chih; Lin, Kun-Yao; Tsai, Wu-Wei; Chiang, Wen-Jen; Yan, Jing-Yi

2013-07-01

This letter investigates the effect of temperature on hot-carrier stress-induced degradation behavior in InGaZnO thin film transistors. After hot-carrier stress at 25 °C, serious on-current and subthreshold swing degradations are observed due to trap state generation near the drain side. For identical stress performed at elevated temperatures, current degradation in the I-V transfer curve under reverse mode is gradually suppressed and the anomalous hump in the gate-to-drain capacitance-voltage curve becomes more severe. These suppressed degradations and the more severe hump can be both attributed to hole-trapping near the drain side due to high drain bias at high temperature.

Detection of gain enhancement in laser-induced fluorescence of rhodamine B lasing dye by silicon dioxide nanostructures-coated cavity

NASA Astrophysics Data System (ADS)

Al-Tameemi, Mohammed N. A.

2018-03-01

In this work, nanostructured silicon dioxide films are deposited by closed-field unbalanced direct-current (DC) reactive magnetron sputtering technique on two sides of quartz cells containing rhodamine B dye dissolved in ethanol with 10‒5 M concentration as a random gain medium. The preparation conditions are optimized to prepare highly pure SiO2 nanostructures with a minimum particle size of about 20 nm. The effect of SiO2 films as external cavity for the random gain medium is determined by the laser-induced fluorescence of this medium, and an increase of about 200% in intensity is observed after the deposition of nanostructured SiO2 thin films on two sides of the dye cell.

Pharmacologic overview of systemic chlorogenic acid therapy on experimental wound healing.

PubMed

Bagdas, Deniz; Gul, Nihal Yasar; Topal, Ayse; Tas, Sibel; Ozyigit, Musa Ozgur; Cinkilic, Nilufer; Gul, Zulfiye; Etoz, Betul Cam; Ziyanok, Sedef; Inan, Sevda; Turacozen, Ozge; Gurun, Mine Sibel

2014-11-01

Chlorogenic acid (CGA) is a well-known natural antioxidant in human diet. To understand the effects of CGA on wound healing by enhancing antioxidant defense in the body, the present study sought to investigate the potential role of systemic CGA therapy on wound healing and oxidative stress markers of the skin. We also aimed to understand whether chronic CGA treatment has side effects on pivotal organs or rat bone marrow during therapy. Full-thickness experimental wounds were created on the backs of rats. CGA (25, 50, 100, 200 mg/kg) or vehicle was administered intraperitoneally for 15 days. All rats were sacrificed on the 16th day. Biochemical, histopathological, and immunohistochemical examinations were performed. Possible side effects were also investigated. The results suggested that CGA accelerated wound healing in a dose-dependent manner. CGA enhanced hydroxyproline content, decreased malondialdehyde and nitric oxide levels. and elevated reduced glutathione, superoxide dismutase, and catalase levels in wound tissues. Epithelialization, angiogenesis, fibroblast proliferation, and collagen formation increased by CGA while polymorph nuclear leukocytes infiltration decreased. CGA modulated matrix metalloproteinase-9 and tissue inhibitor-2 expression in biopsies. Otherwise, high dose of CGA increased lipid peroxidation of liver and kidney without affecting the heart and muscle samples. Chronic CGA increased micronuclei formation and induced cytotoxicity in the bone marrow. In conclusion, systemic CGA has beneficial effects in improving wound repair. Antioxidant, free radical scavenger, angiogenesis, and anti-inflammatory effects of CGA may ameliorate wound healing. High dose of CGA may induce side effects. In light of these observations, CGA supplementation or dietary CGA may have benefit on wound healing.

Bradykinesia induced by frequency-specific pallidal stimulation in patients with cervical and segmental dystonia.

PubMed

Huebl, Julius; Brücke, Christof; Schneider, Gerd-Helge; Blahak, Christian; Krauss, Joachim K; Kühn, Andrea A

2015-07-01

Pallidal deep brain stimulation (DBS) is an effective treatment for patients with primary dystonia leading to a substantial reduction of symptom severity. However, stimulation induced side effects such as bradykinesia have also been reported recently. The influence of stimulation parameters on such side effects have not yet been systemically assessed in these patients. Here we tested the effect of stimulation frequency and duration of stimulation period on hand motor function in 22 patients with primary cervical and segmental dystonia using an unimanual tapping task. Patients performed the task at 4 different stimulation frequencies (0 Hz = OFF stimulation, 20, 50 and ≥130 Hz = high frequency stimulation) after either an SHORT (5 min, N = 16) or a LONG (60 min, N = 6) stimulation period (i.e. changing of DBS-frequency). The change of overall mobility under HFS compared to the preoperative state was assessed with a 5-point Likert-scale. Tapping performance was analysed using a repeated measures ANOVA with the main factor 'FREQUENCY'. Tapping performance at HFS and changes in general mobility were correlated using Spearman's Rho. We found a frequency specific modulation of hand motor function: HFS led to deterioration and 20 Hz stimulation to improvement of tapping rate. The effects were predominant in the 'LONG' group suggesting a significant contribution of stimulation duration. This is important to consider during DBS-programming and evaluation of potential side effects. Furthermore, the impairment in hand motor function under HFS was mirrored by the patients' observation of a deterioration of general mobility. Copyright © 2015 Elsevier Ltd. All rights reserved.

Therapeutic potential of cannabinoids in counteracting chemotherapy-induced adverse effects: an exploratory review.

PubMed

Ostadhadi, Sattar; Rahmatollahi, Mahdieh; Dehpour, Ahmad-Reza; Rahimian, Reza

2015-03-01

Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy-associated bone loss, chemotherapy-induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy-induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed. Copyright © 2014 John Wiley & Sons, Ltd.

Switching to moclobemide to reverse fluoxetine-induced sexual dysfunction in patients with depression.

PubMed Central

Ramasubbu, R

1999-01-01

OBJECTIVE: To determine the efficacy of substituting moclobemide, a reversible monoamine oxidase-A inhibitor, for fluoxetine to reverse fluoxetine-induced sexual dysfunction in patients with depression. DESIGN: Prospective open trial. SETTING: Outpatient treatment. PARTICIPANTS: Five patients with depressive disorder who experienced sexual side effects during treatment with standard doses of fluoxetine (20 to 40 mg per day). INTERVENTION: Discontinuation of fluoxetine and replacement with moclobemide (300 to 600 mg per day) after a 2-week washout period. OUTCOME MEASURES: Libido, orgasmic function (in women) or erectile and ejaculatory function (in men), and overall improvement in sexual function during a follow-up period of 2 months to 3 years. RESULTS: Among patients receiving fluoxetine questioned about sexual side effects, 4 (1 man and 3 women) had treatment-related diminished libido with poor orgasmic response or partial erectile failure, and 1 female patient had enhanced sexual desire with intense clitoral stimulation. In all patients, sexual disturbances resolved completely after a 2-week washout period and a switch to treatment with moclobemide. Moclobemide was well tolerated. The antidepressant effect of moclobemide was comparable to that of fluoxetine. CONCLUSIONS: Moclobemide may be preferred as a treatment for depression in patients with fluoxetine-induced sexual dysfunction. PMID:9987207

Irinotecan-loaded double-reversible thermogel with improved antitumor efficacy without initial burst effect and toxicity for intramuscular administration.

PubMed

Din, Fakhar Ud; Kim, Dong Wuk; Choi, Ju Yeon; Thapa, Raj Kumar; Mustapha, Omer; Kim, Dong Shik; Oh, Yu-Kyoung; Ku, Sae Kwang; Youn, Yu Seok; Oh, Kyung Taek; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

2017-05-01

Intramuscularly administered, anti-tumour drugs induce severe side effects due to their direct contact with body tissues and initial burst effect. In this study, to solve this problem, a novel double-reversible thermogel system (DRTG) for the intramuscular administration of irinotecan was developed. This irinotecan-loaded DRTG was prepared by dispersing the irinotecan-loaded thermoreversible solid lipid nanoparticles (SLNs) in the thermoreversible hydrogel. In DRTG, the former was solid at 25°C but converted to liquid at 36.5°C; in contrast, the latter existed in a liquid form but transformed to gel state in the body. The DRTG was easily administered intramuscularly. Its particle size and drug content were not noticeably changeable, resulting that it was stable at 40°C for at least 6months. Compared to the irinotecan-loaded solution and conventional hydrogel, the DRTG significantly delayed drug release, leading to a reduced burst effect. Moreover, it showed decreased C max and maintained the sustained plasma concentrations at a relatively low level for the long period of 60h in rats, resulting in ameliorated side effects of the anti-tumour drug. Furthermore, it gave significantly improved anti-tumour efficacy in tumour-bearing mice compared to the hydrogel but, unlike the conventional hydrogel, induced no body weight loss and local damage to the muscle. Thus, this DRTG with improved antitumor efficacy without initial burst effect and toxicity could provide a potential pharmaceutical system for the intramuscular administration of irinotecan. Intramuscularly administered, anti-tumour drugs induce severe side effects due to their direct contact with body tissues and initial burst effect. To solve this problem, we developed a novel double-reversible thermogel system (DRTG) for the intramuscular administration of irinotecan. Unlike the conventional hydrogel, the DRTG is a dispersion of the irinotecan-loaded thermoreversible solid lipid nanoparticles in the thermoreversible hydrogel. In DRTG, the former was solid at 25°C but converted to liquid at 36.5°C; in contrast, the latter existed in a liquid form but transformed to gel state in the body. This DRTG gave significantly improved anti-tumour efficacy in tumour-bearing mice compared to the hydrogel but, unlike the conventional hydrogel, induced no body weight loss and local damage to the muscle. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Protective effect of Bu-zhong-yi-qi decoction, the water extract of Chinese traditional herbal medicine, on 5-fluorouracil-induced renal injury in mice.

PubMed

Xiong, Ying; Shang, Bingzhen; Xu, Siying; Zhao, Ran; Gou, He; Wang, Chun

2016-09-01

Drug-induced renal injury is a serious toxic side effect of 5-fluorouracil (5-FU) treatment. Bu-zhong-yi-qi decoction (BZYQD), a water extract of Chinese traditional herbal medicine, is widely used in Asia as an alternative treatment to reduce the side effects of chemotherapy and also improve cancer survival. However, the mechanism is unknown. This study is designed to investigate the protective effect of BZYQD on 5-FU-induced renal injury in mice. Mice were divided into four groups: the control, 5-FU, 5-FU + low, and high BZYQD group. Mice in the three latter groups were administered 5-FU (100 mg/kg/day, intraperitoneally) for six days, and in the 5-FU + low and high BZYQD groups were given BZYQD (1 or 2 g raw herb/kg/day, intragastrically) beginning four days before 5-FU and continuing until the termination of the experiment. The right kidney fixed in formalin for histological examination and the left was homogenized to measure the levels of apoptosis-related proteins and activities of oxidative stress-related biomarkers. Blood samples were collected for measuring renal function-related biochemical indices. Renal morphology injury, increased urea nitrogen and creatinine concentration, and decreased SOD, CAT, and GSH-Px were all observed in 5-FU-administrated mice. However, BZYQD almost reversed the morphological injury as well as renal function-related indices and antioxidant enzyme activity. These results suggest that BZYQD inhibits 5-FU-induced renal injury, possibly through the reduction of apoptosis and necrosis in renal tubular epithelial cells via the antioxidant mechanism. Henceforth, BZYQD may be a potential antioxidant against drug-induced oxidative stress.

Activation of anorexigenic pro-opiomelanocortin neurones during refeeding is independent of vagal and brainstem inputs.

PubMed

Fekete, C; Zséli, G; Singru, P S; Kádár, A; Wittmann, G; Füzesi, T; El-Bermani, W; Lechan, R M

2012-11-01

After fasting, satiety is observed within 2 h after reintroducing food, accompanied by activation of anorexigenic, pro-opiomelanocortin (POMC)-synthesising neurones in the arcuate nucleus (ARC), indicative of the critical role that α-melanocyte-stimulating hormone has in the regulation of meal size during refeeding. To determine whether refeeding-induced activation of POMC neurones in the arcuate is dependent upon the vagus nerve and/or ascending brainstem pathways, bilateral subdiaphragmatic vagotomy or transection of the afferent brainstem input to one side of the ARC was performed. One day after vagotomy or 2 weeks after brain surgery, animals were fasted and then refed for 2 h. Sections containing the ARC from vagotomised animals or animals with effective transection were immunostained for c-Fos and POMC to detect refeeding-induced activation of POMC neurones. Quantitative analyses of double-labelled preparations demonstrated that sham-operated and vagotomised animals markedly increased the number of c-Fos-immunoreactive (-IR) POMC neurones with refeeding. Furthermore, transection of the ascending brainstem pathway had no effect on diminishing c-Fos-immunoreactivity in POMC neurones on either side of the ARC, although it did diminish activation in a separate, subpopulation of neurones in the dorsomedial posterior ARC (dmpARC) on the transected side. We conclude that inputs mediated via the vagus nerve and/or arising from the brainstem do not have a primary role in refeeding-induced activation of POMC neurones in the ARC, and propose that these neurones may be activated solely by direct effects of circulating hormones/metabolites during refeeding. Activation of the dmpARC by refeeding indicates a previously unrecognised role for these neurones in appetite regulation in the rat. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

Hyperammonemic coma after craniotomy: Hepatic encephalopathy from upper gastrointestinal hemorrhage or valproate side effect?: Case report and literature review.

PubMed

Guo, Xiaopeng; Wei, Junji; Gao, Lu; Xing, Bing; Xu, Zhiqin

2017-04-01

Postoperative coma is not uncommon in patients after craniotomy. It generally presents as mental state changes and is usually caused by intracranial hematoma, brain edema, or swelling. Hyperammonemia can also result in postoperative coma; however, it is rarely recognized as a potential cause in coma patients. Hyperammonemic coma is determined through a complicated differential diagnosis, and although it can also be induced as a side effect of valproate (VPA), this cause is frequently unrecognized or confused with upper gastrointestinal hemorrhage (UGH)-induced hepatic encephalopathy. We herein present a case of valproate-induced hyperammonemic encephalopathy (VHE) to illustrate the rarity of such cases and emphasize the importance of correct diagnosis and proper treatment. A 61-year-old woman with meningioma was admitted into our hospital. Radical resection of the tumor was performed, and the patient recovered well as expected. After administration of valproate for 7 days, the patient was suddenly found in a deep coma, and her mental state deteriorated rapidly. The diagnoses of hepatic encephalopathy was confirmed. However, whether it origins from upper gastrointestinal hemorrhage or valproate side effect is uncertain. The patient's condition fluctuated without improvement during the subsequent 3 days under the treatment of reducing ammonia. With the discontinuation of valproate treatment, the patient regained complete consciousness within 48 hours, and her blood ammonia decreased to the normal range within 4 days. VHE is a rare but serious complication in patients after craniotomy and is diagnosed by mental state changes and elevated blood ammonia. Thus, the regular perioperative administration of VPA, which is frequently neglected as a cause of VHE, should be emphasized. In addition, excluding UGH prior to providing a diagnosis and immediately discontinuing VPA administration are recommended.

N-Methyl, N-propynyl-2-phenylethylamine (MPPE), a Selegiline Analog, Attenuates MPTP-induced Dopaminergic Toxicity with Guaranteed Behavioral Safety: Involvement of Inhibitions of Mitochondrial Oxidative Burdens and p53 Gene-elicited Pro-apoptotic Change.

PubMed

Shin, Eun-Joo; Nam, Yunsung; Lee, Ji Won; Nguyen, Phuong-Khue Thi; Yoo, Ji Eun; Tran, The-Vinh; Jeong, Ji Hoon; Jang, Choon-Gon; Oh, Young J; Youdim, Moussa B H; Lee, Phil Ho; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2016-11-01

Selegiline is a monoamine oxidase-B (MAO-B) inhibitor with anti-Parkinsonian effects, but it is metabolized to amphetamines. Since another MAO-B inhibitor N-Methyl, N-propynyl-2-phenylethylamine (MPPE) is not metabolized to amphetamines, we examined whether MPPE induces behavioral side effects and whether MPPE affects dopaminergic toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Multiple doses of MPPE (2.5 and 5 mg/kg/day) did not show any significant locomotor activity and conditioned place preference, whereas selegiline (2.5 and 5 mg/kg/day) significantly increased these behavioral side effects. Treatment with MPPE resulted in significant attenuations against decreases in mitochondrial complex I activity, mitochondrial Mn-SOD activity, and expression induced by MPTP in the striatum of mice. Consistently, MPPE significantly attenuated MPTP-induced oxidative stress and MPPE-mediated antioxidant activity appeared to be more pronounced in mitochondrial-fraction than in cytosolic-fraction. Because MPTP promoted mitochondrial p53 translocation and p53/Bcl-xL interaction, it was also examined whether mitochondrial p53 inhibitor pifithrin-μ attenuates MPTP neurotoxicity. MPPE, selegiline, or pifithrin-μ significantly attenuated mitochondrial p53/Bcl-xL interaction, impaired mitochondrial transmembrane potential, cytosolic cytochrome c release, and cleaved caspase-3 in wild-type mice. Subsequently, these compounds significantly ameliorated MPTP-induced motor impairments. Neuroprotective effects of MPPE appeared to be more prominent than those of selegiline. MPPE or selegiline did not show any additional protective effects against the attenuation by p53 gene knockout, suggesting that p53 gene is a critical target for these compounds. Our results suggest that MPPE possesses anti-Parkinsonian potentials with guaranteed behavioral safety and that the underlying mechanism of MPPE requires inhibition of mitochondrial oxidative stress, mitochondrial translocation of p53, and pro-apoptotic process.

Interactions between antiepileptic drugs and hormones.

PubMed

Svalheim, Sigrid; Sveberg, Line; Mochol, Monika; Taubøll, Erik

2015-05-01

Antiepileptic drugs (AEDs) are known to have endocrine side effects in both men and women. These can affect fertility, sexuality, thyroid function, and bone health, all functions of major importance for well-being and quality of life. The liver enzyme inducing antiepileptic drugs (EIAEDs), like phenobarbital, phenytoin, and carbamazepine, and also valproate (VPA), a non-EIAED, are most likely to cause such side effects. AED treatment can alter the levels of different sex hormones. EIAEDs increase sex hormone binding globulin (SHBG) concentrations in both men and women. Over time, this elevation can lead to lower levels of bioactive testosterone and estradiol, which may cause menstrual disturbances, sexual problems, and eventually reduced fertility. VPA can cause weight gain in both men and women. In women, VPA can also lead to androgenization with increased serum testosterone concentrations, menstrual disturbances, and polycystic ovaries. Lamotrigine has not been shown to result in endocrine side effects. The newer AEDs have not yet been thoroughly studied, but case reports indicate that some of these drugs could also be suspected to cause such effects if endocrine changes commence after treatment initiation. It is important to be aware of possible endocrine side effects of AEDs as they can have a major impact on quality of life, and are, at least partly, reversible after AED discontinuation. Copyright © 2015. Published by Elsevier Ltd.

Effect of cAMP on short-circuit current in isolated human ciliary body.

PubMed

Wu, Ren-yi; Ma, Ning; Hu, Qian-qian

2013-07-01

Cyclic adenosine monophosphate (cAMP) could activate chloride channels in bovine ciliary body and trigger an increase in the ionic current (short-circuit current, Isc) across the ciliary processes in pigs. The purpose of this study was to investigate how cAMP modulates Isc in isolated human ciliary processes and the possible involvement of chloride transport across the tissue in cAMP-induced Isc change. In an Ussing-type chamber system, the Isc changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase activator forskolin in isolated human ciliary processes were assessed. The involvement of Cl(-) component in the bath solution was investigated. The effect of Cl(-) channel (10 µmol/L niflumic acid and 1 mmol/L 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)), K(+) channel (10 mmol/L tetraethylammonium chloride (TEA)), or Na(+) channel blockers (1 mmol/L amiloride) on 8-bromo-cAMP-induced Isc change was also studied. Dose-dependently, 8-bromo-cAMP (10 nmol/L-30 µmol/L) or forskolin (10 nmol/L-3 µmol/L) increased Isc across the ciliary processes with an increase in negative potential difference on the non-pigmented epithelium (NPE) side of the tissue. Isc increase induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE side than on the pigmented epithelium side. When the tissue was bathed in low Cl(-) solutions, the Isc increase was significantly inhibited. Finally, niflumic acid and DIDS, but not TEA or amiloride, significantly prevented the Isc increase induced by 8-bromo-cAMP. cAMP stimulates stroma-to-aqueous anionic transport in isolated human ciliary processes. Chloride is likely to be among the ions, the transportation of which across the tissue is triggered by cAMP, suggesting the potential role of cAMP in the process of aqueous humor formation in human eyes.

Effect of piezocision on root resorption associated with orthodontic force: A microcomputed tomography study.

PubMed

Patterson, Braydon M; Dalci, Oyku; Papadopoulou, Alexandra K; Madukuri, Suman; Mahon, Jonathan; Petocz, Peter; Spahr, Axel; Darendeliler, M Ali

2017-01-01

The purpose of this study was to investigate the effect of piezocision on orthodontically induced inflammatory root resorption. Fourteen patients were included in this split-mouth study; 1 side was assigned to piezocision, and the other side served as the control. Vertical corticotomy cuts of 4 to 5 mm in length were performed on either side of each piezocision premolar, and 150-g buccal tipping forces were applied to the premolars. After 4 weeks, the maxillary first premolars were extracted and scanned with microcomputed tomography. There was a significantly greater total amount of root resorption seen on the piezocision sides when compared with the control sides (P = 0.029). The piezocision procedure resulted in a 44% average increase in root resorption. In 5 patients, there was noticeable piezocision-related iatrogenic root damage. When that was combined with the orthodontic root resorption found on the piezocision-treated teeth, there was a statistically significant 110% average increase in volumetric root loss when compared with the control side (P = 0.005). The piezocision procedure that initiates the regional acceleratory phenomenon may increase the iatrogenic root resorption when used in conjunction with orthodontic forces. Piezocision applied close to the roots may cause iatrogenic damage to the neighboring roots and should be used carefully. Copyright © 2017.

Differential effects of left and right neuropathy on opioid gene expression in lumbar spinal cord.

PubMed

Kononenko, Olga; Mityakina, Irina; Galatenko, Vladimir; Watanabe, Hiroyuki; Bazov, Igor; Gerashchenko, Anna; Sarkisyan, Daniil; Iatsyshyna, Anna; Yakovleva, Tatiana; Tonevitsky, Alex; Marklund, Niklas; Ossipov, Michael H; Bakalkin, Georgy

2018-05-28

The endogenous opioid system (EOS) controls the processing of nociceptive stimuli and is a pharmacological target for opioids. Alterations in expression of the EOS genes under neuropathic pain condition may account for low efficacy of opioid drugs. We here examined whether EOS expression patterns are altered in the lumbar spinal cord of the rats with spinal nerve ligation (SNL) as a neuropathic pain model. Effects of the left- and right-side SNL on expression of EOS genes in the ipsi- and contralateral spinal domains were analysed. The SNL-induced changes were complex and different between the genes; between the dorsal and ventral spinal domains; and between the left and right sides of the spinal cord. Prodynorphin (Pdyn) expression was upregulated in the ipsilateral dorsal domains by each the left and right-side SNL, while changes in expression of μ-opioid receptor (Oprm1) and proenkephalin (Penk) genes were dependent on the SNL side. Changes in expression of the Pdyn and κ-opioid receptor (Oprk1) genes were coordinated between the ipsi- and contralateral sides. Withdrawal response thresholds, indicators of mechanical allodynia correlated negatively with Pdyn expression in the right ventral domain after right side SNL. These findings suggest multiple roles of the EOS gene products in spinal sensitization and changes in motor reflexes, which may differ between the left and right sides. Copyright © 2018. Published by Elsevier B.V.

Distal end side-to-side anastomoses of sequential vein graft to small target coronary arteries improve intraoperative graft flow

PubMed Central

2014-01-01

Background End-to-side anastomoses to connect the distal end of the great saphenous vein (GSV) to small target coronary arteries are commonly performed in sequential coronary artery bypass grafting (CABG). However, the oversize diameter ratio between the GSV and small target vessels at end-to-side anastomoses might induce adverse hemodynamic condition. The purpose of this study was to describe a distal end side-to-side anastomosis technique and retrospectively compare the effect of distal end side-to-side versus end-to-side anastomosis on graft flow characteristics. Methods We performed side-to-side anastomoses to connect the distal end of the GSV to small target vessels on 30 patients undergoing off-pump sequential CABG in our hospital between October 2012 and July 2013. Among the 30 patients, end-to-side anastomoses at the distal end of the GSV were initially performed on 14 patients; however, due to poor graft flow, those anastomoses were revised into side-to-side anastomoses. We retrospectively compared the intraoperative graft flow characteristics of the end-to-side versus side-to-side anastomoses in the 14 patients. The patient outcomes were also evaluated. Results We found that the side-to-side anastomosis reconstruction improved intraoperative flow and reduced pulsatility index in all the 14 patients significantly. The 16 patients who had the distal end side-to-side anastomoses performed directly also exhibited satisfactory intraoperative graft flow. Three-month postoperative outcomes for all the patients were satisfactory. Conclusions Side-to-side anastomosis at the distal end of sequential vein grafts might be a promising strategy to connect small target coronary arteries to the GSV. PMID:24884776

Capillary zone electrophoresis determination of aniline and pyridine in sewage samples using transient isotachophoresis with a system-induced terminator.

PubMed

Hattori, Takanari; Okamura, Hideo; Asaoka, Satoshi; Fukushi, Keiichi

2017-08-18

Transient isotachophoresis (tITP) with a system-induced terminator (SIT) was developed for capillary zone electrophoresis (CZE) determination of aniline (An + ) and pyridine (Py + ) in sewage samples. After sample injection, a water vial was set at the sample-inlet side. Then voltage was applied to generate a system-induced terminator (H + ). Experiments and simulations revealed a concentration effect by tITP with an SIT: background electrolyte (BGE) - 100mM acetic acid (AcOH) and 50mM NaOH (pH 4.6); detection wavelength - 200nm for An + and 254nm for Py + ; vacuum injection period - 15s (190nL); SIT generation - 10kV applied for 80s with the sample inlet side anode; separation voltage - 20kV with the sample inlet side anode. The limits of detection (LODs, S/N=3) of An + and Py + respectively reached 10 and 42μg/L, with good repeatability (peak area RSDs≤6.9%) and calibration graph linearity (R 2 =0.9997). The proposed method was applied for determination of An + and Py + in sewage samples. Recoveries of An + (0.50mg/L) and Py + (2.0mg/L) in spiked sewage samples were 94-104%. Copyright © 2017 Elsevier B.V. All rights reserved.

Sibutramine in the treatment of antipsychotic-induced weight gain: a pilot study in patients with schizophrenia.

PubMed

Biedermann, Falko; Fleischhacker, W Wolfgang; Kemmler, Georg; Ebenbichler, Christoph F; Lechleitner, Monika; Hofer, Alex

2014-05-01

Weight gain represents a frequent side effect of antipsychotic drug treatment. The current trial investigated the effect of add-on treatment with sibutramine in schizophrenia outpatients who had gained more than 7% of weight during the course of treatment. This 24-week placebo-controlled study evaluated the effects of sibutramine added to ongoing antipsychotic treatment. Weight, waist-hip ratio, BMI, blood pressure/pulse and ECG were monitored regularly. In addition, several laboratory tests were performed. Psychopathological symptoms and side effects were assessed frequently. Fifteen patients were assigned randomly to add-on treatment with sibutramine 10 mg or placebo. The two groups did not differ in weight, sociodemographic, or clinical data. Eleven patients were considered for statistical analysis. Significant weight loss was observed in the sibutramine group (mean = -6.1 kg), whereas patients on placebo experienced a mean weight gain of 1.9 kg. A reduction in HbA1c was apparent in the sibutramine but not in the placebo group. No significant between-group differences were found in changes in psychopathology or drug safety. This pilot trial suggests that adjunctive treatment with sibutramine may be safe and effective in schizophrenic patients with antipsychotic-induced weight gain.

Radiation-induced vaginal stenosis: current perspectives

PubMed Central

Morris, Lucinda; Do, Viet; Chard, Jennifer; Brand, Alison H

2017-01-01

Treatment of gynecological cancer commonly involves pelvic radiation therapy (RT) and/or brachytherapy. A commonly observed side effect of such treatment is radiation-induced vaginal stenosis (VS). This review analyzed the incidence, pathogenesis, clinical manifestation(s) and assessment and grading of radiation-induced VS. In addition, risk factors, prevention and treatment options and follow-up schedules are also discussed. The limited available literature on many of these aspects suggests that additional studies are required to more precisely determine the best management strategy of this prevalent group after RT. PMID:28496367

GraphSAW: a web-based system for graphical analysis of drug interactions and side effects using pharmaceutical and molecular data.

PubMed

Shoshi, Alban; Hoppe, Tobias; Kormeier, Benjamin; Ogultarhan, Venus; Hofestädt, Ralf

2015-02-28

Adverse drug reactions are one of the most common causes of death in industrialized Western countries. Nowadays, empirical data from clinical studies for the approval and monitoring of drugs and molecular databases is available. The integration of database information is a promising method for providing well-based knowledge to avoid adverse drug reactions. This paper presents our web-based decision support system GraphSAW which analyzes and evaluates drug interactions and side effects based on data from two commercial and two freely available molecular databases. The system is able to analyze single and combined drug-drug interactions, drug-molecule interactions as well as single and cumulative side effects. In addition, it allows exploring associative networks of drugs, molecules, metabolic pathways, and diseases in an intuitive way. The molecular medication analysis includes the capabilities of the upper features. A statistical evaluation of the integrated data and top 20 drugs concerning drug interactions and side effects is performed. The results of the data analysis give an overview of all theoretically possible drug interactions and side effects. The evaluation shows a mismatch between pharmaceutical and molecular databases. The concordance of drug interactions was about 12% and 9% of drug side effects. An application case with prescribed data of 11 patients is presented in order to demonstrate the functionality of the system under real conditions. For each patient at least two interactions occured in every medication and about 8% of total diseases were possibly induced by drug therapy. GraphSAW (http://tunicata.techfak.uni-bielefeld.de/graphsaw/) is meant to be a web-based system for health professionals and researchers. GraphSAW provides comprehensive drug-related knowledge and an improved medication analysis which may support efforts to reduce the risk of medication errors and numerous drastic side effects.

Effect of soluble guanylyl cyclase activator and stimulator therapy on nitroglycerin-induced nitrate tolerance in rats.

PubMed

Jabs, A; Oelze, M; Mikhed, Y; Stamm, P; Kröller-Schön, S; Welschof, P; Jansen, T; Hausding, M; Kopp, M; Steven, S; Schulz, E; Stasch, J-P; Münzel, T; Daiber, A

2015-08-01

Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the present study aims at investigating the effects of the therapy with the sGC activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced by chronic nitroglycerin treatment. Male Wistar rats were treated with nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or 2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770 but not with BAY 41-8543 improved nitroglycerin-triggered endothelial dysfunction and nitrate tolerance, corrected the decrease in aortic nitric oxide levels, improved the cGMP dependent activation of protein kinase I in aortic tissue and reduced vascular, cardiac and whole blood oxidative stress (fluorescence and chemiluminescence assays; 3-nitrotyrosine staining). In contrast to BAY 41-8543, the vasodilator potency of BAY 60-2770 was not impaired in isolated aortic ring segments from nitrate tolerant rats. sGC activator therapy improves partially the adverse effects of nitroglycerin therapy whereas sGC stimulation has only minor beneficial effects pointing to a nitroglycerin-dependent sGC oxidation/inactivation mechanism contributing to nitrate tolerance. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls.

PubMed

Kontulainen, Saija; Sievänen, Harri; Kannus, Pekka; Pasanen, Matti; Vuori, Ilkka

2003-02-01

Bone characteristics of the humeral shaft and distal radius were measured from 64 female tennis and squash players and their 27 age-, height-, and weight-matched controls with peripheral quantitative tomography (pQCT) and dual energy X-ray absorptiometry (DXA). The players were divided into two groups according to the starting age of their tennis or squash training (either before or after menarche) to examine the possible differences in the loading-induced changes in bone structure and volumetric density. The following pQCT variables were used: bone mineral content, total cross-sectional area of bone (TotA), cross-sectional area of the marrow cavity (CavA) and that of the cortical bone (CoA), cortical wall thickness (CWT), volumetric density of the cortical bone (CoD) and trabecular bone (TrD), and torsional bone strength index for the shaft (BSIt) and compressional bone strength index for the bone end (BSIc). These bone strength indices were compared with the DXA-derived areal bone mineral density (aBMD) to assess how well the latter represents the effect of mechanical loading on apparent bone strength. At the humeral shaft, the loaded arm's greater bone mineral content (an average 19% side-to-side difference in young starters and 9% in old starters), was caused by an enlarged cortex (CoA; side-to-side differences 20% and 9%, respectively). The loaded humerus seemed to have grown periosteally (the CavA did not differ between the sites), leading to 26% and 11% side-to-side BSIt differences in the young and old starters, respectively. CoD was equal between the arms (-1% difference in both player groups). The side-to-side differences in the young starters' bone mineral content, CoA, TotA, CWT, and BSIt were 8-22% higher than those of the controls and 8-14% higher than those of the old starters. Old starters' bone mineral content, CoA, and BSIt side-to-side differences were 6-7% greater than those in the controls. The DXA-derived side-to-side aBMD difference was 7% greater in young starters compared with that of the old starters and 14% compared with that in controls, whereas the difference between old starters and controls was 6%, in favor of the former. All these between-group differences were statistically significant. At the distal radius, the player groups differed significantly from controls in the side-to-side bone mineral content, TrD, and aBMD differences only: the young starters' bone mineral content difference was 9% greater, TrD and aBMD differences were 5% greater than those in the controls, and the old starters' TrD and aBMD differences were both 7% greater than those in the controls. In summary, in both of the female player groups, the structural adaptation of the humeral shaft to long-term loading seemed to be achieved through periosteal enlargement of the bone cortex, although this adaptation was clearly better in the young starters. Exercise-induced cortical enlargement was not so clear at the distal radius (a trabecular bone site), and the study suggested that at long bone ends, the trabecular density could be a modifiable factor to built a stronger bone structure. Conventional DXA-based aBMD measurement detected the intergroup differences in the exercise-induced bone gains, although, because it measured two dimensions of bone only, it seemed to underestimate the effect of exercise on the apparent bone strength, especially if the playing had been started during the growing years.

Inhibition of 5a-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation

PubMed Central

Devoto, Paola; Frau, Roberto; Bini, Valentina; Pillolla, Giuliano; Saba, Pierluigi; Flore, Giovanna; Corona, Marta; Marrosu, Francesco; Bortolato, Marco

2012-01-01

Summary Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5α-reductase (5αR), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic-like effects in humans and animal models, without inducing extrapyramidal side effects. To elucidate the anatomical substrates mediating these effects, we investigated the contribution of peripheral and neural structures to the behavioral effects of the 5αR inhibitor finasteride (FIN) on the prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a rat paradigm that dependably simulates the sensorimotor gating impairments observed in schizophrenia and other neuropsychiatric disorders. The potential effect of drug-induced ASR modifications on PPI was excluded by measuring this index both as percent (%PPI) and absolute values (ΔPPI). In both orchidectomized and sham-operated rats, FIN prevented the %PPI deficits induced by the dopamine (DA) receptor agonists apomorphine (APO, 0.25 mg/kg, SC) and d-amphetamine (AMPH, 2.5 mg/kg, SC), although the latter effect was not corroborated by ΔPPI analysis. Conversely, APO-induced PPI deficits were countered by FIN infusions in the brain ventricles (10 μg/1 μl) and in the nucleus accumbens (NAc) shell and core (0.5 μg/0.5 μl/side). No significant PPI-ameliorating effect was observed following FIN injections in other brain regions, including dorsal caudate, basolateral amygdala, ventral hippocampus and medial prefrontal cortex, although a statistical trend was observed for the latter region. The efflux of DA in NAc was increased by systemic, but not intracerebral FIN administration. Taken together, these findings suggest that the role of 5αR in gating regulation is based on post-synaptic mechanisms in the NAc, and is not directly related to alterations in DA efflux in this region. PMID:22029952

Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cetiner, Mustafa; Sener, Goeksel; Sehirli, A. Ozer

2005-11-15

The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed tomore » measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-{alpha} level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics.« less

Orally active Epac inhibitor reverses mechanical allodynia and loss of intraepidermal nerve fibers in a mouse model of chemotherapy-induced peripheral neuropathy.

PubMed

Singhmar, Pooja; Huo, XiaoJiao; Li, Yan; Dougherty, Patrick M; Mei, Fang; Cheng, Xiaodong; Heijnen, Cobi J; Kavelaars, Annemieke

2018-05-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of cancer treatment that significantly compromises quality of life of cancer patients and survivors. Identification of targets for pharmacological intervention to prevent or reverse CIPN is needed. We investigated exchange protein regulated by cAMP (Epac) as a potential target. Epacs are cAMP-binding proteins known to play a pivotal role in mechanical allodynia induced by nerve injury and inflammation. We demonstrate that global Epac1-knockout (Epac1-/-) male and female mice are protected against paclitaxel-induced mechanical allodynia. In addition, spinal cord astrocyte activation and intraepidermal nerve fiber (IENF) loss are significantly reduced in Epac1-/- mice as compared to wild-type mice. Moreover, Epac1-/- mice do not develop the paclitaxel-induced deficits in mitochondrial bioenergetics in the sciatic nerve that are a hallmark of CIPN. Notably, mice with cell-specific deletion of Epac1 in Nav1.8-positive neurons (N-Epac1-/-) also show reduced paclitaxel-induced mechanical allodynia, astrocyte activation, and IENF loss, indicating that CIPN develops downstream of Epac1 activation in nociceptors. The Epac-inhibitor ESI-09 reversed established paclitaxel-induced mechanical allodynia in wild-type mice even when dosing started 10 days after completion of paclitaxel treatment. In addition, oral administration of ESI-09 suppressed spinal cord astrocyte activation in the spinal cord and protected against IENF loss. Ex vivo, ESI-09 blocked paclitaxel-induced abnormal spontaneous discharges in dorsal root ganglion neurons. Collectively, these findings implicate Epac1 in nociceptors as a novel target for treatment of CIPN. This is clinically relevant because ESI-09 has the potential to reverse a debilitating and long-lasting side effect of cancer treatment.

Electrolytic lesion of the nucleus raphe magnus reduced the antinociceptive effects of bilateral morphine microinjected into the nucleus cuneiformis in rats.

PubMed

Haghparast, Abbas; Ordikhani-Seyedlar, Mehdi; Ziaei, Maryam

2008-06-27

Several lines of investigation show that the rostral ventromedial medulla is a critical relay for midbrain regions, including the nucleus cuneiformis (CnF), which control nociception at the spinal cord. There is some evidence that local stimulation or morphine administration into the CnF produces the effective analgesia through the nucleus raphe magnus (NRM). The present study tries to determine the effect of morphine-induced analgesia following microinjection into the CnF in the absence of NRM. Seven days after the cannulae implantation, morphine was microinjected bilaterally into the CnF at the doses of 0.25, 1, 2.5, 5, 7.5 and 10 microg/0.3 microl saline per side. The morphine-induced antinociceptive effect measured by tail-flick test at 30, 60, 90 and 120 min after microinjection. The results showed that bilateral microinjection of morphine into the CnF dose-dependently causes increase in tail-flick latency (TFL). The 50% effective dose of morphine was determined and microinjected into the CnF (2.5 microg/0.3 microl saline per side) in rats after NRM electrolytic lesion (1 mA, 30 s). Lesion of the NRM significantly decreased TFLs, 30 (P<0.01) and 60 (P<0.05) but not 90-120 min after morphine microinjection into the CnF, compared with sham-lesion group. We concluded that morphine induces the analgesic effects through the opioid receptors in the CnF. It is also appeared that morphine-induced antinociception decreases following the NRM lesion but it seems that there are some other descending pain modulatory pathways that activate in the absence of NRM.

Designer aminoglycosides that selectively inhibit cytoplasmic rather than mitochondrial ribosomes show decreased ototoxicity: a strategy for the treatment of genetic diseases.

PubMed

Shulman, Eli; Belakhov, Valery; Wei, Gao; Kendall, Ann; Meyron-Holtz, Esther G; Ben-Shachar, Dorit; Schacht, Jochen; Baasov, Timor

2014-01-24

There is compelling evidence that aminoglycoside (AG) antibiotics can induce the mammalian ribosome to suppress disease-causing nonsense mutations and partially restore the expression of functional proteins. However, prolonged AG treatment can cause detrimental side effects in patients, including most prominently, ototoxicity. Recent mechanistic discussions have considered the relative contributions of mitochondrial and cytoplasmic protein synthesis inhibition to AG-induced ototoxicity. We show that AGs inhibit mitochondrial protein synthesis in mammalian cells and perturb cell respiration, leading to a time- and dose-dependent increase in superoxide overproduction and accumulation of free ferrous iron in mitochondria caused by oxidative damage of mitochondrial aconitase, ultimately leading to cell apoptosis via the Fenton reaction. These deleterious effects increase with the increased potency of AG to inhibit the mitochondrial rather than cytoplasmic protein synthesis, which in turn correlates with their ototoxic potential in both murine cochlear explants and the guinea pig in vivo. The deleterious effects of AGs were alleviated in synthetic derivatives specially designed for the treatment of genetic diseases caused by nonsense mutations and possessing low affinity toward mitochondrial ribosomes. This work highlights the benefit of a mechanism-based drug redesign strategy that can maximize the translational value of "readthrough therapy" while mitigating drug-induced side effects. This approach holds promise for patients suffering from genetic diseases caused by nonsense mutations.

On-demand anakinra treatment is effective in mevalonate kinase deficiency.

PubMed

Bodar, E J; Kuijk, L M; Drenth, J P H; van der Meer, J W M; Simon, A; Frenkel, J

2011-12-01

Mevalonate kinase deficiency (MKD) is a hereditary autoinflammatory syndrome marked by recurrent attacks of fever and inflammation. Severe enzyme deficiency results in mevalonic aciduria (MA) and milder deficiency in hyperimmunoglobulin D syndrome (HIDS). Treatment remains a challenge. To observe the effect of the recombinant interleukin-1 receptor antagonist anakinra in patients with MKD. A prospective observational study was undertaken. Two patients with MA started continuous treatment with anakinra (1-2 mg/kg/day) and nine patients with HIDS chose between continuous treatment and on-demand treatment (starting at first symptoms of attack, 100 mg/day or 1 mg/kg/day for 5-7 days). Anakinra induced partial remission in one patient with MA but there was no response in the other patient with MA. In one patient with HIDS continuous treatment induced complete remission for 7 months but was stopped because of side effects. Eight patients with HIDS preferred on-demand treatment from the start. This induced a clinical response (≥50% reduction in duration) in 8 of 12 treated attacks without a change in attack frequency. Anakinra prevented fever attacks due to vaccination without inhibiting antibody induction. No major side effects were seen. On-demand treatment with anakinra in HIDS decreases the duration and severity of fever attacks. Because of the burden of daily injections and relatively long asymptomatic intervals of HIDS, all patients with HIDS preferred on-demand treatment.

Aminopenicillin-induced exanthema allows treatment with certain cephalosporins or phenoxymethyl penicillin.

PubMed

Trcka, Jiri; Seitz, Cornelia S; Bröcker, Eva-B; Gross, Gerd E; Trautmann, Axel

2007-07-01

Aminopenicillin-induced exanthema poses a problem in the management of infectious diseases. Due to theoretically possible immunological cross-reactivity, all beta-lactam drugs, i.e. penicillins, penicillin derivatives and cephalosporins, are usually avoided. The available alternative antibiotics (macrolides, quinolones and glycopeptides) may be less effective, have more side effects, and their use increases medical costs. Moreover, their use contributes to the increasing bacterial resistance to antibiotics. The aim of the study is to demonstrate that patients with aminopenicillin-induced exanthema may receive specific beta-lactams for future antibiotic therapy. Skin testing followed by oral challenges to identify beta-lactams that are tolerated by patients despite confirmed delayed-type non-immunoglobulin E (IgE)-mediated allergic hypersensitivity to aminopenicillins. Sixty-nine out of 71 patients (97.2%) with non-IgE-mediated allergic hypersensitivity to aminopenicillins tolerate cephalosporins without an aminobenzyl side chain such as cefpodoxime or cefixime and 51 patients (71.8%) also tolerate phenoxymethyl penicillin. The majority of patients with non-IgE-mediated allergic hypersensitivity to aminopenicillins do not cross-react to certain cephalosporins or phenoxymethyl penicillin. Skin and drug challenge tests can be helpful to determine individual cross-reactivity.

Pavlovian conditioning of nausea and vomiting.

PubMed

Stockhorst, Ursula; Steingrueber, Hans-Joachim; Enck, Paul; Klosterhalfen, Sibylle

2006-10-30

Cancer patients undergoing cytotoxic drug treatment often experience side-effects, the most distressing being nausea and vomiting. Despite antiemetic drugs, 25-30% of the chemotherapy patients report these side-effects when being re-exposed to the stimuli that usually signal the chemotherapy session and its drug infusion. These symptoms are called anticipatory nausea and anticipatory vomiting. The present paper summarizes the evidence that anticipatory vomiting is acquired by Pavlovian conditioning, and, consequently, may be alleviated by conditioning techniques. To explore the mechanisms that induce and alleviate conditioned nausea and vomiting further, a conditioned nausea model was established in healthy humans using body rotation as the nausea-inducing treatment. The validity of this motion sickness model to examine conditioning mechanisms in the acquisition and alleviation of conditioned nausea was demonstrated. Cortisol and tumor-necrosis factor-alpha were elevated as endocrine and immunological correlates of nausea. Data in the rotation-induced motion sickness model indicated that gender is an important moderator variable to be considered in further studies. The paper concludes with a review of applications of the demonstrated conditioning principles as interventions to ameliorate distressing anticipatory nausea or anticipatory vomiting in cancer patients undergoing chemotherapy.

Improvement in Capsule Abort Performance Using Supersonic Aerodynamic Interaction by Fences

NASA Astrophysics Data System (ADS)

Koyama, Hiroto; Wang, Yunpeng; Ozawa, Hiroshi; Doi, Katsunori; Nakamura, Yoshiaki

The space transportation system will need advanced abort systems to secure crew against serious accidents. Here this study deals with the capsule-type space transportation systems with a Launch Abort System (LAS). This system is composed of a conic capsule as a Launch Abort Vehicle (LAV) and a cylindrical rocket as a Service Module (SM), and the capsule is moved away from the rocket by supersonic aerodynamic interactions in an emergency. We propose a method to improve the performance of the LAV by installing fences at the edges of surfaces on the rocket and capsule sides. Their effects were investigated by experimental measurements and numerical simulations. Experimental results show that the fences on the rocket and capsule surfaces increase the aerodynamic thrust force on the capsule by 70% in a certain clearance between the capsule and rocket. Computational results show the detailed flow fields where the centripetal flow near the surface on the rocket side is induced by the fence on the rocket side and the centrifugal flow near the surface on the capsule side is blocked by the fence on the capsule side. These results can confirm favorable effects of the fences on the performance of the LAS.

Kava and valerian in the treatment of stress-induced insomnia.

PubMed

Wheatley, D

2001-09-01

Kava and valerian are herbal remedies, claimed to have anxiolytic and sedative properties respectively, without dependence potential or any appreciable side-effects. In this pilot study, 24 patients suffering from stress-induced insomnia were treated for 6 weeks with kava 120 mg daily. This was followed by 2 weeks off treatment and then, 5 having dropped out, 19 received valerian 600 mg daily for another 6 weeks. Stress was measured in three areas: social, personal and life-events; insomnia in three areas also: time to fall asleep, hours slept and waking mood. Total stress severity was significantly relieved by both compounds (p < 0.01) with no significant differences between them; as was also insomnia (p < 0.01). The proportion of patients with no side-effects was 58% with each drug respectively and the 'commonest' effect was vivid dreams with valerian (16%), followed by dizziness with kava (12% ). These compounds may be useful in the treatment of stress and insomnia but further studies are required to determine their relative roles for such indications. Copyright 2001 John Wiley & Sons, Ltd.

Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

PubMed Central

Chu, Yung-Lin; Raghu, Rajasekaran; Lu, Kuan-Hung; Liu, Chun-Ting; Lin, Shu-Hsi; Lai, Yi-Syuan; Cheng, Wei-Cheng; Lin, Shih-Hang; Sheen, Lee-Yan

2013-01-01

Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic (Dà Suàn; Allium sativum), is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients. PMID:24716172

Long-term safety and efficacy of budesonide in the treatment of ulcerative colitis

PubMed Central

Iborra, Marisa; Álvarez-Sotomayor, Diego; Nos, Pilar

2014-01-01

Ulcerative colitis (UC) is a chronic, relapsing, and remitting inflammatory disease involving the large intestine (colon). Treatment seeks to break recurrent inflammation episodes by inducing and maintaining remission. Historically, oral systemic corticosteroids played an important role in inducing remission of this chronic disease; however, their long-term use is limited and can lead to adverse events. Budesonide is a synthetic steroid with potent local anti-inflammatory effects and low systemic bioavailability due to high first-pass hepatic metabolism. Several studies have demonstrated oral budesonide’s usefulness in treating active mild to moderate ileocecal Crohn’s disease and microscopic colitis and in an enema formulation for left sided UC. However, there is limited information regarding oral budesonide’s efficacy in UC. A novel oral budesonide formulation using a multimatrix system (budesonide-MMX) to extend drug release throughout the colon has been developed recently and seems to be an effective treatment in active left sided UC patients. This article summarizes budesonide’s long-term safety and efficacy in treating UC. PMID:24523594

Autophagy therapeutic potential of garlic in human cancer therapy.

PubMed

Chu, Yung-Lin; Raghu, Rajasekaran; Lu, Kuan-Hung; Liu, Chun-Ting; Lin, Shu-Hsi; Lai, Yi-Syuan; Cheng, Wei-Cheng; Lin, Shih-Hang; Sheen, Lee-Yan

2013-07-01

Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic (Dà Suàn; Allium sativum), is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients.

Psychosis induced by the interaction between disulfiram and methylphenidate may be dose dependent.

PubMed

Grau-López, Lara; Roncero, Carlos; Navarro, Maria C; Casas, Miquel

2012-01-01

There are few studies describing psychiatric symptoms occurring when methylphenidate and disulfiram are used together. The authors report a case of disulfiram and methylphenidate interaction in which psychotic symptoms could be dose dependent. The patient, diagnosed of alcohol and cocaine dependence and attention deficit hyperactivity disorder (ADHD), started treatment with methylphenidate increasing doses and disulfiram 250 mg/day over 4 weeks. During the first 2 weeks at doses of 36 mg/day of methylphenidate and maintaining disulfiram, side effects were not observed. However, by increasing to 54 mg/day, psychotic symptoms were detected. The authors reported that the effects are dose dependent. This is the first report about dose-dependent side effects in substance use disorder with ADHD.

Topical minoxidil in the treatment of alopecia areata.

PubMed Central

Fenton, D A; Wilkinson, J D

1983-01-01

A modified double blind crossover study was performed to assess the effect of 1% topical minoxidil as compared with placebo in 30 patients with alopecia areata and alopecia totalis. The active preparation produced a highly significant incidence of hair regrowth. A cosmetically acceptable response was noted in 16 patients. No side effects were seen. The study confirmed that topical minoxidil will induce new hair growth in alopecia areata but that it is less likely to do so in more severe and extensive disease. Furthermore, patients with alopecia universalis and totalis may not respond at all. Nevertheless, as compared with other drugs minoxidil applied topically is relatively non-toxic, is easy to use, and has no systemic or local side effects. Images p1016-a PMID:6412929

Next generation immunotherapy for tree pollen allergies.

PubMed

Su, Yan; Romeu-Bonilla, Eliezer; Heiland, Teri

2017-10-03

Tree pollen induced allergies are one of the major medical and public health burdens in the industrialized world. Allergen-Specific Immunotherapy (AIT) through subcutaneous injection or sublingual delivery is the only approved therapy with curative potential to pollen induced allergies. AIT often is associated with severe side effects and requires long-term treatment. Safer, more effective and convenient allergen specific immunotherapies remain an unmet need. In this review article, we discuss the current progress in applying protein and peptide-based approaches and DNA vaccines to the clinical challenges posed by tree pollen allergies through the lens of preclinical animal models and clinical trials, with an emphasis on the birch and Japanese red cedar pollen induced allergies.

Long-term risks of psoralen and UV-A therapy for psoriasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farber, E.M.; Abel, E.A.; Cox, A.J.

1983-05-01

It has been more than eight years since photochemotherapy with methoxsalen and UV-A (psoralen and UV-A (PUVA)) was introduced for the treatment of psoriasis. This treatment remained under investigation until May 1982 because of concerns about possible chronic toxic effects. With recent Food and Drug Administration approval of PUVA therapy for severe psoriasis, strict drug labeling for administration and patient use and continued monitoring of side effects have become essential. The full effects of PUVA in regard to carcinogenicity, prematurelly induced aging of the skin, pigmentary changes, immunologic alterations, and ocular side effects are still unknown. A review of themore » risks of PUVA therapy is presented, with the aim of maintaining a proper perspective for its limited use in treating selected patients.« less

Clinical practice guidelines on the evidence-based use of integrative therapies during and following breast cancer treatment

PubMed Central

Greenlee, Heather; DuPont-Reyes, Melissa J.; Balneaves, Lynda G.; Carlson, Linda E.; Cohen, Misha R.; Deng, Gary; Johnson, Jillian A.; Mumber, Matthew; Seely, Dugald; Zick, Suzanna; Boyce, Lindsay; Tripathy, Debu

2018-01-01

Patients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatment-related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mind-body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. PMID:28436999

Theoretical study of piezo-phototronic nano-LEDs.

PubMed

Liu, Ying; Niu, Simiao; Yang, Qing; Klein, Benjamin D B; Zhou, Yu Sheng; Wang, Zhong Lin

2014-11-12

Two-dimensional finite-element simulation of the piezo-phototronic effect in p-n-junction-based devices is carried out for the first time. A charge channel can be induced at the p-n junction interface when strain is applied, given the n-side is a piezoelectric semiconductor and the p-type side is non-piezoelectric semiconductor. This provides the first simulated evidence supporting the previously suggested mechanism responsible for the experimentally observed gigantic change of light-emission efficiency in piezo-phototronic light-emitting devices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acute hemifacial dystonia possibly induced by clebopride.

PubMed

Bosco, Domenico; Plastino, Massimiliano; Marcello, Maria Giovanna; Mungari, Pasquale; Fava, Antonietta

2009-01-01

Dystonic reactions produce twisting and repetitive movements or abnormal posturing. Severe dystonic reactions have been shown to occur in concert with numerous medications. This report details the case of a patient who developed hemifacial dystonia as acute side reaction from administration of clebopride for dyspeptic prophylaxis. When the drug was immediately stopped, the dystonic posture disappeared completely within 2 weeks. The use of clebopride may be associated with not only a reversible or persistent parkinsonism syndrome but also hemifacial dystonia; therefore, attention must be drawn to this possible side effect.

Nilotinib Induced Recurrent Gastric Polyps: Case Report and Review of Literature.

PubMed

Kassem, Nancy; Ismail, Omar M; Elomri, Halima; Yassin, Mohamad A

2017-07-14

BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment. We excluded common causes of gastric polyps and therefore considered nilotinib as a probable cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be a potential side effect of nilotinib treatment. Careful long-term monitoring of patients on TKI therapy is necessary and further long-term studies of TKI side effects are needed.

R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

PubMed Central

Yang, C; Shirayama, Y; Zhang, J-c; Ren, Q; Yao, W; Ma, M; Dong, C; Hashimoto, K

2015-01-01

Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)–TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF–TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF–TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability. PMID:26327690

Effects of modified short-leg walkers on ground reaction force characteristics.

PubMed

Keefer, Maria; King, Jon; Powell, Douglas; Krusenklaus, John H; Zhang, Songning

2008-11-01

Although short-leg walkers are often used in the treatment of lower extremity injuries (ankle and foot fractures and severe ankle sprains), little is known about the effect the short-leg walker on gait characteristics. The purpose was to examine how heel height modifications in different short-leg walkers and shoe side may affect ground reaction forces in walking. Force platforms were used to collect ground reaction force data on 10 healthy participants. Five trials were performed in each of six conditions: lab shoes, gait walker, gait walker with heel insert on shoe side, gait walker modified with insert on walker side, equalizer walker, and equalizer walker with heel insert on shoe side. Conditions were randomized and walking speed was standardized between conditions. A 2x6 (sidexcondition) repeated analysis of variance was used on selected ground reaction force variables (P<0.05). The application of a walker created peak vertical and anteroposterior ground reaction forces prior to the normal peaks associated with the loading response. Wearing a walker introduced an elevated minimum vertical ground reaction force in all conditions except the equalizer walker when compared to shoe on the shoe side. Peak propulsive anteroposterior ground reaction forces were smaller in all walker conditions compared to shoe on walker side. The application of heel insert in gait walker with heel insert (on shoe side) and gait walker modified (on walker side) does not diminish the minimum vertical ground reaction force as hypothesized. Wearing a walker decreases the peak propulsive anteroposterior ground reaction force on the walker side and induces asymmetrical loading.

Binding of cationic pentapeptides with modified side chain lengths to negatively charged lipid membranes: Complex interplay of electrostatic and hydrophobic interactions.

PubMed

Hoernke, Maria; Schwieger, Christian; Kerth, Andreas; Blume, Alfred

2012-07-01

Basic amino acids play a key role in the binding of membrane associated proteins to negatively charged membranes. However, side chains of basic amino acids like lysine do not only provide a positive charge, but also a flexible hydrocarbon spacer that enables hydrophobic interactions. We studied the influence of hydrophobic contributions to the binding by varying the side chain length of pentapeptides with ammonium groups starting with lysine to lysine analogs with shorter side chains, namely omithine (Orn), alpha, gamma-diaminobutyric acid (Dab) and alpha, beta-diaminopropionic acid (Dap). The binding to negatively charged phosphatidylglycerol (PG) membranes was investigated by calorimetry, FT-infrared spectroscopy (FT-IR) and monolayer techniques. The binding was influenced by counteracting and sometimes compensating contributions. The influence of the bound peptides on the lipid phase behavior depends on the length of the peptide side chains. Isothermal titration calorimetry (ITC) experiments showed exothermic and endothermic effects compensating to a different extent as a function of side chain length. The increase in lipid phase transition temperature was more significant for peptides with shorter side chains. FTIR-spectroscopy revealed changes in hydration of the lipid bilayer interface after peptide binding. Using monolayer techniques, the contributions of electrostatic and hydrophobic effects could clearly be observed. Peptides with short side chains induced a pronounced decrease in surface pressure of PG monolayers whereas peptides with additional hydrophobic interactions decreased the surface pressure much less or even lead to an increase, indicating insertion of the hydrophobic part of the side chain into the lipid monolayer.

Protective effects of persian honey, Apis Mellifera Meda Skorikov on side effects of chemotherapy and ischemia/reperfusion induced testicular injury.

PubMed

Gholami, Mohammadreza; Abbaszadeh, Abolfazl; Baharvand, Parastoo; Hasanvand, Afshin; Hasanvand, Amin; Gharravi, Anneh Mohammad

2018-05-23

Introduction The aim of the present study was to survey the protective effect of pretreatment with Persian honey on amelioration of side effects of chemotherapy and ischemia/reperfusion induced testicular injury. Materials and methods Forty adult's male wistar rats were divided into four groups of ischemia-reperfusion (IR), honey + ischemia-reperfusion (HIR), Busulfan (B) and Busulfan intraperitoneally+ honey (BH). The seminiferous tubules were rated for their modified spermatogenesis index (SI) by Johnsons score. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed using the in-situ cell death detection kit. Total serum concentration of Follicle-stimulating hormone (FSH) , Luteinizing hormone (LH) and testosterone was measured using ELISA. All data were expressed as mean ± SD and significance was set at p≤0.05. Results Honey improved SI in the HIR and BH groups and serum levels of FSH and LH in the BH and HIR groups (p<0.001). Also, serum levels of testosterone were significantly higher in BH and HIR groups. But, apoptotic cells in IR and B groups significantly increased (p<0.001), while in HIR and BH groups, the number of apoptotic cells decreased and the positive cells of TUNEL (TdT-mediated dUTP-X nick end labelling) staining were detected in spermatocytes and spermatid. Discussion Pretreatment with honey protect testis against chemotherapy and testicular IR injury, increase FSH and LH and testosterone and decrease the cellular damage and apoptosis. Honey can decrease the side effects of chemotherapy on reproductive system and prevent sterility.

Macrocytic anemia and thrombocytopenia induced by orlistat.

PubMed

Palacios-Martinez, David; Garcia-Alvarez, Juan Carlos; Montero-Santamaria, Nieves; Villar-Ruiz, Olga Patricia; Ruiz-Garcia, Antonio; Diaz-Alonso, Raquel Asuncion

2013-10-01

The overall incidence of obesity and its prevalence is increasing continuously. The obesity is a cardiovascular risk factor whose importance is increasing too. It is associated with many chronic conditions such as type II diabetes mellitus or cardiovascular diseases. The obesity is also implicated as a risk factor for several kinds of cancer such as esophagus, pancreas, colon, rectum, breast cancer in menopausal women. The treatment of the obesity may reduce the incidence of these diseases. The mainstray of the treatment of obesity is changing the lifestyles, but obesity´s treatment may need drug therapy or even though surgical treatment. Orlistat is a specific inhibitor of gastrointestinal lipases, which stops fat absortion. It is used along with a hypocaloric diet, for obesity´s treatment. The beneficial effects of orlistat include weight loss, the improvement of blood pressure´s control, it may delay the development of diabetes mellitus, and it may reduce HbA1c. Besides the interaction with other drugs (mainly warfarin and amiodarone). Orlistat´s mainly side effects are gastrointestinal disorders such as the existence of oily spotting from the rectum, abdominal pain or discomfort, fecal urgency. There are also side effects at other levels, like flu symptoms, hypoglycemia, heathache or upper respiratory infections. There are other side effects with very low incidence but clinically relevant like pancreatitis, subacute liver failure, severe liver disease, myopathy, or tubular necrosis secondary to oxalate nephropathy induced by Orlistat. IN THIS CASE REPORT APPEARS A NEW ADVERSE EFFECT OF ORLISTAT THAT HAS NOT BEEN DESCRIBED ABOVE: thrombopenia and macrocytic anemia.

Pinellia ternata Attenuates Mucus Secretion and Airway Inflammation after Inhaled Corticosteroid Withdrawal in COPD Rats.

PubMed

Du, Wei; Su, Jinyu; Ye, Dan; Wang, Yuegang; Huang, Qiaobing; Gong, Xiaowei

2016-01-01

Inhaled corticosteroids (ICS) are widely used to manage chronic obstructive pulmonary disease (COPD). However, withdrawal of ICS generally causes various adverse effects, warranting careful management of the ICS withdrawal. Pinellia ternata, a traditional Chinese herbal medicine, has been used to treat respiratory diseases in China for centuries. Here, we investigated its role in antagonizing ICS withdrawal-induced side effects, and explored the underlying mechanisms. The rat COPD model was established using a combination of passive cigarette smoking and intratracheal instillation of lipopolysaccharide (LPS). COPD rats were treated with saline or budesonide inhalation, or with budesonide inhalation followed by saline inhalation or Pinellia ternata gavage. The number of goblet cells and the level of mucin 5AC (MUC5AC) were enhanced by budesonide withdrawal. Pinellia ternata treatment significantly blocked these effects. Further, Pinellia ternata treatment reversed budesonide withdrawal-induced increase of interleukin 1[Formula: see text] (IL-1[Formula: see text] and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]) levels in bronchoalveolar lavage fluid (BALF). Extracellular signal-regulated kinase (ERK), but neither p38 nor c-Jun N-terminal kinase (JNK), was activated by budesonide withdrawal, and the activation was blocked by Pinellia ternata treatment. The MUC5AC expression was positively correlated with goblet cell number, IL-1[Formula: see text] and TNF-[Formula: see text] levels, and ERK activity. Pinellia ternata treatment protected the airway from ICS withdrawal-induced mucus hypersecretion and airway inflammation by inhibiting ERK activation. Pinellia ternata treatment may represent a novel therapeutic strategy to prevent ICS withdrawal-induced side effects in COPD patients.

Deficiency of the bulk spin Hall effect model for spin-orbit torques in magnetic-insulator/heavy-metal heterostructures

NASA Astrophysics Data System (ADS)

Li, Junxue; Yu, Guoqiang; Tang, Chi; Liu, Yizhou; Shi, Zhong; Liu, Yawen; Navabi, Aryan; Aldosary, Mohammed; Shao, Qiming; Wang, Kang L.; Lake, Roger; Shi, Jing

2017-06-01

Electrical currents in a magnetic-insulator/heavy-metal heterostructure can induce two simultaneous effects, namely, spin Hall magnetoresistance (SMR) on the heavy-metal side and spin-orbit torques (SOTs) on the magnetic-insulator side. Within the framework of a pure spin current model based on the bulk spin Hall effect (SHE), the ratio of the spin Hall-induced anomalous Hall effect (SH-AHE) to SMR should be equal to the ratio of the fieldlike torque (FLT) to the dampinglike torque (DLT). We perform a quantitative study of SMR, SH-AHE, and SOTs in a series of thulium iron garnet/platinum or T m3F e5O12/Pt heterostructures with different T m3F e5O12 thicknesses, where T m3F e5O12 is a ferrimagnetic insulator with perpendicular magnetic anisotropy. We find the ratio between the measured effective fields of FLT and DLT is at least two times larger than the ratio of the SH-AHE to SMR. In addition, the bulk SHE model grossly underestimates the spin-torque efficiency of FLT. Our results reveal deficiencies of the bulk SHE model and also address the importance of interfacial effects such as the Rashba and magnetic proximity effects in magnetic-insulator/heavy-metal heterostructures.

Measurement of behavior of secondary sealing areas of rotary engine apex seals - Two-piece nonsplit and three-piece slanted horizontal split types

NASA Astrophysics Data System (ADS)

Matsuura, Kenji; Terasaki, Kazuo; Yamane, Katsuki

1992-12-01

Behavior measurements have been made with two displacement sensors and an underseal pressure sensor, using an overhanging eccentric shaft-type single-rotor research engine equipped with a packaged multichannel slip ring. The two-piece seal was tilted to the leading and trailing sides of a seal slot during its travel along the rotor housing surface and vibrated on the top end of the leading side of the slot as a fulcrum after the shift from the trailing to the leading side of the slot after the minor axis on the spark plug side. As for the three-piece seal, its top part was also tilted in all operating conditions, although its bottom part made effective area contact with the side of the slot under light load conditions up to medium engine speeds. The working chamber pressure was induced in the underseal in the same manner as with the two-piece type.

Sleep self-intoxication and sleep driving as rare zolpidem-induced complex behaviour.

PubMed

Paulke, Alexander; Wunder, Cora; Toennes, Stefan W

2015-01-01

The GABA(A) receptor agonist zolpidem has been used for treatment of insomnia since years, but special side effects have been reported. These side effects were called zolpidem-induced sleep-related complex behaviour. Such complex behaviour is associated with somnambulism and includes sleepwalking, sleep eating, sleep conversation and sleep driving. Two cases of zolpidem-induced sleep-related complex behaviour following self-intoxication, sleep driving and amnesia are presented. In both cases, the subjects reported the voluntary intake of only one zolpidem tablet of 10 mg and amnesia for the time afterwards. Shortly after the onset of the drug's action, both individuals drifted into a somnambulism-like state and toxicological blood analysis suggested the intake of the remaining zolpidem tablets which might be called "sleep intoxication". Later, the subjects were arrested by police after driving under drug influence and not realizing the situation. Retrospectively, both subjects suffered from psychiatric disorders and in case 2, the subject was treated for depression with doxepin. Consequently, these co-factors may have increased the risk for the occurrence of the sleep-related complex behaviour. Involuntary self-intoxication should be taken into account in addition to the known pattern of zolpidem-induced complex behaviour. In legal cases, the forensic expert has to assess the blood concentration of zolpidem in evaluating this strange behaviour. Amnesia and incoherence of speech, disorganization of behaviour, inability to realize the situation and mood changes may indicate a zolpidem-induced somnambulism-like state with sleep-related complex behaviour.

An fMRI study of acupuncture-induced brain activation of aphasia stroke patients.

PubMed

Li, Geng; Yang, Edward S

2011-01-01

This investigation aims to test the effect of acupuncture on word generation activation (WGA) in post-stroke aphasia patients. Seven vascular aphasia patients and 14 control subjects were studied using functional magnetic resonance imaging (fMRI). Each performed: (1) a word generation (WG) task alone, followed by (2) repeating WG after insertion of acupuncture needles (WGN) into SJ 8 (a language-implicated acupoint), followed by (3) repeating WGN reinforced by electrical stimulation (WGA) of SJ 8, and finally (4) electrical stimulation (ES) of SJ 8 alone. Significant activation was found in the opercular, triangular, or insula during the ES stimulation in patients when comparing each patient to 14 normal controls. For the WG task, significant activation was found in the inferior frontal gyrus when comparing each patient to 14 normal controls. The signal induced by acupuncture was larger than that of the WG task in the left middle frontal gyrus with the comparison of WGA vs. WGN in seven patients. Further, main significant effects in the right insula in patients were observed when comparing seven patients to 14 normal controls. The activation induced by ES stimulation was only found on the left side in controls. This activation was observed on the lesion side of superior and middle frontal gyrus (SMFG) in patients. This study demonstrates for the first time that language-deficit-implicated acupoint stimulation can selectively activate the brain on the lesion side in post-stroke aphasia patients. These results suggest that acupuncture may have therapeutic benefits in post-stroke aphasia patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Chiral Sulfoxide-Induced Single Turn Peptide α-Helicity

PubMed Central

Zhang, Qingzhou; Jiang, Fan; Zhao, Bingchuan; Lin, Huacan; Tian, Yuan; Xie, Mingsheng; Bai, Guoyun; Gilbert, Adam M.; Goetz, Gilles H.; Liras, Spiros; Mathiowetz, Alan A.; Price, David A.; Song, Kun; Tu, Meihua; Wu, Yujie; Wang, Tao; Flanagan, Mark E.; Wu, Yun-Dong; Li, Zigang

2016-01-01

Inducing α-helicity through side-chain cross-linking is a strategy that has been pursued to improve peptide conformational rigidity and bio-availability. Here we describe the preparation of small peptides tethered to chiral sulfoxide-containing macrocyclic rings. Furthermore, a study of structure-activity relationships (SARs) disclosed properties with respect to ring size, sulfur position, oxidation state, and stereochemistry that show a propensity to induce α-helicity. Supporting data include circular dichroism spectroscopy (CD), NMR spectroscopy, and a single crystal X-ray structure for one such stabilized peptide. Finally, theoretical studies are presented to elucidate the effect of chiral sulfoxides in inducing backbone α-helicity. PMID:27934919

Are There Side Effects to Watching 3D Movies? A Prospective Crossover Observational Study on Visually Induced Motion Sickness

PubMed Central

Solimini, Angelo G.

2013-01-01

Background The increasing popularity of commercial movies showing three dimensional (3D) images has raised concern about possible adverse side effects on viewers. Methods and Findings A prospective carryover observational study was designed to assess the effect of exposure (3D vs. 2D movie views) on self reported symptoms of visually induced motion sickness. The standardized Simulator Sickness Questionnaire (SSQ) was self administered on a convenience sample of 497 healthy adult volunteers before and after the vision of 2D and 3D movies. Viewers reporting some sickness (SSQ total score>15) were 54.8% of the total sample after the 3D movie compared to 14.1% of total sample after the 2D movie. Symptom intensity was 8.8 times higher than baseline after exposure to 3D movie (compared to the increase of 2 times the baseline after the 2D movie). Multivariate modeling of visually induced motion sickness as response variables pointed out the significant effects of exposure to 3D movie, history of car sickness and headache, after adjusting for gender, age, self reported anxiety level, attention to the movie and show time. Conclusions Seeing 3D movies can increase rating of symptoms of nausea, oculomotor and disorientation, especially in women with susceptible visual-vestibular system. Confirmatory studies which include examination of clinical signs on viewers are needed to pursue a conclusive evidence on the 3D vision effects on spectators. PMID:23418530

Are there side effects to watching 3D movies? A prospective crossover observational study on visually induced motion sickness.

PubMed

Solimini, Angelo G

2013-01-01

The increasing popularity of commercial movies showing three dimensional (3D) images has raised concern about possible adverse side effects on viewers. A prospective carryover observational study was designed to assess the effect of exposure (3D vs. 2D movie views) on self reported symptoms of visually induced motion sickness. The standardized Simulator Sickness Questionnaire (SSQ) was self administered on a convenience sample of 497 healthy adult volunteers before and after the vision of 2D and 3D movies. Viewers reporting some sickness (SSQ total score>15) were 54.8% of the total sample after the 3D movie compared to 14.1% of total sample after the 2D movie. Symptom intensity was 8.8 times higher than baseline after exposure to 3D movie (compared to the increase of 2 times the baseline after the 2D movie). Multivariate modeling of visually induced motion sickness as response variables pointed out the significant effects of exposure to 3D movie, history of car sickness and headache, after adjusting for gender, age, self reported anxiety level, attention to the movie and show time. Seeing 3D movies can increase rating of symptoms of nausea, oculomotor and disorientation, especially in women with susceptible visual-vestibular system. Confirmatory studies which include examination of clinical signs on viewers are needed to pursue a conclusive evidence on the 3D vision effects on spectators.

Emulsification Increases the Acute Ketogenic Effect and Bioavailability of Medium-Chain Triglycerides in Humans

PubMed Central

Courchesne-Loyer, Alexandre; Lowry, Carolyn-Mary; St-Pierre, Valérie; Vandenberghe, Camille; Fortier, Mélanie; Castellano, Christian-Alexandre; Wagner, J Richard; Cunnane, Stephen C

2017-01-01

Abstract Background: Lower-brain glucose uptake is commonly present before the onset of cognitive deterioration associated with aging and may increase the risk of Alzheimer disease. Ketones are the brain's main alternative energy substrate to glucose. Medium-chain triglycerides (MCTs) are rapidly β-oxidized and are ketogenic but also have gastrointestinal side effects. We assessed whether MCT emulsification into a lactose-free skim-milk matrix [emulsified MCTs (MCT-Es)] would improve ketogenesis, reduce side effects, or both compared with the same oral dose of MCTs consumed without emulsification [nonemulsified MCTs (MCT-NEs)]. Objectives: Our aims were to show that, in healthy adults, MCT-Es will induce higher ketonemia and have fewer side effects than MCT-NEs and the effects of MCT-NEs and MCT-Es on ketogenesis and plasma medium-chain fatty acids (MCFAs) will be dose-dependent. Methods: Using a metabolic study day protocol, 10 healthy adults were each given 3 separate doses (10, 20, or 30 g) of MCT-NEs or MCT-Es with a standard breakfast or no treatment [control (CTL)]. Blood samples were taken every 30 min for 4 h to measure plasma ketones (β-hydroxybutyrate and acetoacetate), octanoate, decanoate, and other metabolites. Participants completed a side-effects questionnaire at the end of each study day. Results: Compared with CTL, MCT-NEs increased ketogenesis by 2-fold with no significant differences between doses. MCT-Es increased total plasma ketones by 2- to 4-fold in a dose-dependent manner. Compared with MCT-NEs, MCT-Es increased plasma MCFA bioavailability (F) by 2- to 3-fold and decreased the number of side effects by ∼50%. Conclusions: Emulsification increased the ketogenic effect and decreased side effects in a dose-dependent manner for single doses of MCTs ≤30 g under matching conditions. Further investigation is needed to establish whether emulsification could sustain ketogenesis and minimize side effects and therefore be used as a treatment to change brain ketone availability over a prolonged period of time. This trial was registered at clinicaltrials.gov as NCT02409927.

Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies

PubMed Central

Oh, Gi-Su; Kim, Hyung-Jin; Shen, AiHua; Lee, Su Bin; Khadka, Dipendra; Pandit, Arpana

2014-01-01

Cisplatin is one of the most widely used and highly effective drug for the treatment of various solid tumors; however, it has dose-dependent side effects on the kidney, cochlear, and nerves. Nephrotoxicity is the most well-known and clinically important toxicity. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced nephrotoxicity. Even though the establishment of cisplatin-induced nephrotoxicity can be alleviated by diuretics and pre-hydration of patients, the prevalence of cisplatin nephrotoxicity is still high, occurring in approximately one-third of patients who have undergone cisplatin therapy. Therefore it is imperative to develop treatments that will ameliorate cisplatin-nephrotoxicity. In this review, we discuss the mechanisms of cisplatin-induced renal toxicity and the new strategies for protecting the kidneys from the toxic effects without lowering the tumoricidal activity. PMID:25606044

Topiramate-induced paresthesia is more frequently reported by migraine than epileptic patients.

PubMed

Sedighi, Behnaz; Shafiei, Kaveh; Azizpour, Iman

2016-04-01

Topiramate is an approved and effective drug in migraine prophylaxis. Paresthesia is the most commonly reported side effect. The primary objective of this study was to compare the frequency of topiramate-induced paresthesia in migraine headache to epileptic patients. Patients with migraine without aura and epilepsy were enrolled in this observational study. All cases were interviewed by telephone about their history of paresthesia. Confounding factors were controlled through logistic regression. The odds ratio of developing topiramate-induced paresthesia in migraine compared to epilepsy patients was 3.4. Three factors were independent contributors to developing topiramate-induced paresthesia: female sex (odds ratio 2.1), topiramate dosage (odds ratio 0.3) and duration of therapy. Our findings indicate an independent association between migraine and development of paresthesia. Migraineurs were more likely than epileptic patients to report paresthesia as topiramate adverse effects. Female sex, treatment duration and topiramate dosage contribute significantly to subsequent development of paresthesia.

The Vibration Analysis of Tube Bundles Induced by Fluid Elastic Excitation in Shell Side of Heat Exchanger

NASA Astrophysics Data System (ADS)

Bao, Minle; Wang, Lu; Li, Wenyao; Gao, Tianze

2017-09-01

Fluid elastic excitation in shell side of heat exchanger was deduced theoretically in this paper. Model foundation was completed by using Pro / Engineer software. The finite element model was constructed and imported into the FLUENT module. The flow field simulation adopted the dynamic mesh model, RNG k-ε model and no-slip boundary conditions. Analysing different positions vibration of tube bundles by selecting three regions in shell side of heat exchanger. The results show that heat exchanger tube bundles at the inlet of the shell side are more likely to be failure due to fluid induced vibration.

Local therapeutic efficacy with reduced systemic side effects by rapamycin-loaded subcapsular microspheres.

PubMed

Falke, Lucas L; van Vuuren, Stefan H; Kazazi-Hyseni, Filis; Ramazani, Farshad; Nguyen, Tri Q; Veldhuis, Gert J; Maarseveen, Erik M; Zandstra, Jurjen; Zuidema, Johan; Duque, Luisa F; Steendam, Rob; Popa, Eliane R; Kok, Robbert Jan; Goldschmeding, Roel

2015-02-01

Kidney injury triggers fibrosis, the final common pathway of chronic kidney disease (CKD). The increase of CKD prevalence worldwide urgently calls for new therapies. Available systemic treatment such as rapamycin are associated with serious side effects. To study the potential of local antifibrotic therapy, we administered rapamycin-loaded microspheres under the kidney capsule of ureter-obstructed rats and assessed the local antifibrotic effects and systemic side effects of rapamycin. After 7 days, microsphere depots were easily identifiable under the kidney capsule. Both systemic and local rapamycin treatment reduced intrarenal mTOR activity, myofibroblast accumulation, expression of fibrotic genes, and T-lymphocyte infiltration. Upon local treatment, inhibition of mTOR activity and reduction of myofibroblast accumulation were limited to the immediate vicinity of the subcapsular pocket, while reduction of T-cell infiltration was widespread. In contrast to systemically administered rapamycin, local treatment did not induce off target effects such as weight loss. Thus subcapsular delivery of rapamycin-loaded microspheres successfully inhibited local fibrotic response in UUO with less systemic effects. Therapeutic effect of released rapamycin was most prominent in close vicinity to the implanted microspheres. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metabolic Syndrome and Antipsychotics: The Role of Mitochondrial Fission/Fusion Imbalance.

PubMed

Del Campo, Andrea; Bustos, Catalina; Mascayano, Carolina; Acuña-Castillo, Claudio; Troncoso, Rodrigo; Rojo, Leonel E

2018-01-01

Second-generation antipsychotics (SGAs) are known to increase cardiovascular risk through several physiological mechanisms, including insulin resistance, hepatic steatosis, hyperphagia, and accelerated weight gain. There are limited prophylactic interventions to prevent these side effects of SGAs, in part because the molecular mechanisms underlying SGAs toxicity are not yet completely elucidated. In this perspective article, we introduce an innovative approach to study the metabolic side effects of antipsychotics through the alterations of the mitochondrial dynamics, which leads to an imbalance in mitochondrial fusion/fission ratio and to an inefficient mitochondrial phenotype of muscle cells. We believe that this approach may offer a valuable path to explain SGAs-induced alterations in metabolic homeostasis.

Metabolic Syndrome and Antipsychotics: The Role of Mitochondrial Fission/Fusion Imbalance

PubMed Central

del Campo, Andrea; Bustos, Catalina; Mascayano, Carolina; Acuña-Castillo, Claudio; Troncoso, Rodrigo; Rojo, Leonel E.

2018-01-01

Second-generation antipsychotics (SGAs) are known to increase cardiovascular risk through several physiological mechanisms, including insulin resistance, hepatic steatosis, hyperphagia, and accelerated weight gain. There are limited prophylactic interventions to prevent these side effects of SGAs, in part because the molecular mechanisms underlying SGAs toxicity are not yet completely elucidated. In this perspective article, we introduce an innovative approach to study the metabolic side effects of antipsychotics through the alterations of the mitochondrial dynamics, which leads to an imbalance in mitochondrial fusion/fission ratio and to an inefficient mitochondrial phenotype of muscle cells. We believe that this approach may offer a valuable path to explain SGAs-induced alterations in metabolic homeostasis. PMID:29740394

Numerical Analysis of Flow-Induced Vibrations in Closed Side Branches

NASA Astrophysics Data System (ADS)

KníŽat, Branislav; Troják, Michal

2011-12-01

Vibrations occuring in closed side branches connected to a main pipe are a frequent problem during pipeline system operation. At the design stage of pipeline systems, this problem is sometimes overlooked or underestimated which can later lead to the shortening of the systems life cycle or may even cause injury. The aim of this paper is a numerical analysis of the start of self-induced vibrations on the edge of a closed side branch. Calculation conditions and obtained results are presented within.

Consumption of Goats’ Milk Protects Mice From Carbon Tetrachloride-Induced Acute Hepatic Injury and Improves the Associated Gut Microbiota Imbalance

PubMed Central

Zhang, Jiachao; Wang, Zhaoxia; Huo, Dongxue; Shao, Yuyu

2018-01-01

Drugs used to treat liver diseases have serious side effects; it is important to search for safe functional foods with hepatoprotective functions and few side effects. In this study, potential hepatoprotective effects of goats’ milk and cows’ milk on mice with CCl4-induced acute hepatic injury were evaluated. We also elucidated the role of goats’ and cows’ milk on the regulation of CCl4-induced gut microbiota imbalance. In mice with liver damage induced by CCl4, administration of goats’ milk for 7 days prior to injection of CCl4 had beneficial effects on the indicators of liver damage within 1 day: the area of liver necrosis was small; activity of alanine transaminase (ALT) and aspartate transaminase (AST) and expression of the genes CYP2E1 and TNF-α were lower than that of model group of mice. By 7 days after CCl4 injection, there were no significant differences in liver damage indicators (ALT, AST, malondialdehyde, superoxide dismutase, and glutathione) between the goats’ milk group, which continued to receive goats’ milk, and the untreated control group of mice showing that goats’ milk continued to protect against liver damage. Throughout the entire experiment, the community of gut microbes from mice in the goats’ milk treatment was more similar to the untreated control group than to the cows’ milk group and the model group, indicating that intake of goats’ milk prior and post-CCl4 injection effectively prevented and alleviated the intestinal microbial disorder that caused by CCl4 in mice. Our research suggests that goats’ milk could be developed as a potential functional food to prevent/protect against liver injury. PMID:29867999

Viscous Fingering on an Immiscible Reactive Interface with Variation of Interfacial Tension

NASA Astrophysics Data System (ADS)

Tsuzuki, Reiko; Nagatsu, Yuichiro; Li, Qian; Chen, Ching-Yao

2017-11-01

The effects of chemical reaction, in which surfactants are produced on the interface of two immiscible fluids, on viscous fingering in a radial Hele-Shaw flow are numerically investigated. The presence of surfactants reduces interfacial tension, which is an important factor to the fingering pattern formation. In the present study, influences of reaction rate and dispersion of produced surfactants, represented respectively by dimensionless parameters of Damkohler number and Peclet number, are evaluated systematically. Secondary fingering instability, e.g., tip-splitting and side-branching, is triggered by chemical reactions. Weaker surface tension generally induces tip-splitting. For the case of high Damkohler number, because of the vortex pairs generated within each finger, surfactant tends to accumulate significantly on the side of finger, so that side-branching is preferred. Nevertheless, side-branching is suppressed in the cases associated with low Peclet number, in which strong dispersion reduces the local variation of surfactant concentration. Considering the coupled effects by Damkohler number and Peclet number, the patterns obtained by the simulations qualitatively agree with the observations in the experiments.

The generation of side force by distributed suction

NASA Technical Reports Server (NTRS)

Roberts, Leonard; Hong, John

1993-01-01

This report provides an approximate analysis of the generation of side force on a cylinder placed horizontal to the flow direction by the application of distributed suction on the rearward side of the cylinder. Relationships are derived between the side force coefficients and the required suction coefficients necessary to maintain attached flow on one side of the cylinder, thereby inducing circulation around the cylinder and a corresponding side force.

Decursin prevents cisplatin-induced apoptosis via the enhancement of antioxidant enzymes in human renal epithelial cells.

PubMed

Kim, Jeong Hwan; Jeong, Soo-Jin; Kwon, Hee-Young; Park, Sang Yoon; Lee, Hyo-Jung; Lee, Hyo-Jeong; Lieske, John Charles; Kim, Sung-Hoon

2010-01-01

Adverse effects, nephrotoxicity and hepatotoxicity, of anticancer drugs such as cisplatin have limited the usage for cancer therapy. Therefore, development or identification of supplement agents in anticancer drugs is attractive to reduce side effects and enhance antitumor activity. Here, we found that decursin isolated from Angelica gigas showed protective effects of cisplatin-induced damage in normal human primary renal epithelial cells (HRCs). We found that decursin significantly blocked cisplatin-induced cytotoxicity by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in HRCs. Further, we found that decursin inhibited sub-G1 and cell death by suppression of cleavage of caspase-3, -9 and poly(ADP-ribose) polymerase (PARP) induced by cisplatin treatment in HRCs. Importantly, decursin effectively restored the activities of Cu/Zn superoxide dismutase (SOD), catalase and glutathione peroxidase in cisplatin-treated HRCs. Taken together, our findings demonstrate that decurcin prevents cisplatin-induced cytotoxicity and apoptosis through the activation of antioxidant enzymes in HRCs and suggest further that combination of decursin might suppressed adverse effects of anticancer drugs in cancer patients.

Sensorimotor rhythm neurofeedback as adjunct therapy for Parkinson's disease.

PubMed

Philippens, Ingrid H C H M; Wubben, Jacqueline A; Vanwersch, Raymond A P; Estevao, Dave L; Tass, Peter A

2017-08-01

Neurofeedback may enhance compensatory brain mechanisms. EEG-based sensorimotor rhythm neurofeedback training was suggested to be beneficial in Parkinson's disease. In a placebo-controlled study in parkinsonian nonhuman primates we here show that sensorimotor rhythm neurofeedback training reduces MPTP-induced parkinsonian symptoms and both ON and OFF scores during classical L-DOPA treatment. Our findings encourage further development of sensorimotor rhythm neurofeedback training as adjunct therapy for Parkinson's disease which might help reduce L-DOPA-induced side effects.

A case of bullous pemphigoid ınduced by vildagliptin.

PubMed

Keseroglu, Havva Ozge; Taş-Aygar, Gamze; Gönül, Müzeyyen; Gököz, Ozay; Ersoy-Evans, Sibel

2017-06-01

Bullous pemfigoid (BP), an autoimmune disorder, can also be induced by some medications. Vildagliptin is a new drug used to treat diabetes mellitus (DM). Recently, a few cases of vildagliptin-induced BP have been described in the literature. We report a patient with BP in which vildagliptin was thought to be as a possible causative agent. The awareness of BP development risk during gliptin therapy can prevent unnecessary usage of systemic drugs with serious side effects.

Suppressive effects of ginsan on the development of allergic reaction in murine asthmatic model.

PubMed

Lim, You-Jin; Na, Hee-Sam; Yun, Yeon-Sook; Choi, Inseon S; Oh, Jong-Suk; Rhee, Joon-Haeng; Cho, Bok-Hee; Lee, Hyun-Chul

2009-01-01

Asthma is a major health problem worldwide, and the morbidity and mortality caused by asthma are on the rise. Corticosteroid therapies for asthma treatment frequently induce many side effects. Therefore, the development of new medicines that have both high efficacy and fewer side effects has been a scientific challenge. Here we tested the effect of ginsan, a polysaccharide derived from Panax ginseng, against allergic reaction in an ovalbumin (OVA)-induced murine asthmatic model in comparison with dexamethasone, and investigated its underlying mechanism. To induce murine asthma, mice were sensitized and challenged with OVA. Ginsan or dexamethasone was administered by injection 3 times a week. Airway hyperresponsiveness, airway inflammation and lung pathology were assessed in order to evaluate the effect of ginsan against asthma. Ginsan treatment reduced airway hyperresponsiveness, remodeling and eosinophilia. These effects of ginsan were equivalent to those of dexamethasone. Ginsan treatment decreased the IL-5 level in the supernatant of cultured splenocytes, while IFN-gamma and serum IgE were not altered. To elucidate the mechanism of ginsan, expression of inflammation-related genes were screened. Interestingly, ginsan treatment upregulated cyclooxygenase (COX)-1 and COX-2 mRNA, and expression of their proteins in the lung were also increased. PGE(2) in the bronchoalveolar lavage fluid was also increased by the ginsan treatment. Lastly, ginsan inhibited the allergic reaction aggravated by COX inhibitor (indomethacin). Ginsan has anti-asthmatic effects, which seem to be partially mediated by enhancing the synthesis of COX gene products. Copyright 2009 S. Karger AG, Basel.

A Case Report of Drug-Induced Thrombocytopenia after Living Donor Liver Transplantation

PubMed Central

ARAI, KEISUKE; KURAMITSU, KAORI; FUKUMOTO, TAKUMI; KIDO, MASAHIRO; TAKEBE, ATSUSHI; TANAKA, MOTOFUMI; KINOSHITA, HISOKA; AJIKI, TETSUO; TOYAMA, HIROCHIKA; ASARI, SADAKI; GOTO, TADAHIRO; KU, YONSON

2016-01-01

There are few descriptions of severe thrombocytopenia during the early postoperative period after liver transplantation, and these have not been fully documented in the literature. Here, we report a case of drug-induced thrombocytopenia requiring transfusion of blood products after living donor liver transplantation. We determined that this was not caused by the interferon-free anti-viral therapy but by tacrolimus A 61-year-old woman with hepatitis C-related cirrhosis and hepatorenal syndrome underwent living donor liver transplantation using a left lobe graft from her son. After transplantation, immunosuppression consisted of tacrolimus and steroid. Seven weeks after transplantation, interferon-free therapy with daclatasvir and asunaprevir was started. Thirteen days thereafter, hepatitis C virus tested negative. However, the platelet count had begun to gradually decrease just before starting anti-viral therapy. Daclatasvir and asunaprevir were stopped because this was suspected to be a side-effect of these drugs, but the patient nonetheless went on to develop severe thrombocytopenia (platelet count 17,000/μL), which needed transfusions. Now suspecting tacrolimus as the inducer of this side effect, we changed to cyclosporin, after which the platelet count gradually recovered. Viral markers were still not detectable up to 2 months after discontinuation of the antiviral drugs. We conclude that when severe thrombocytopenia occurs, possible drug-induced thrombocytopenia as well as other disorders must be investigated. PMID:27492209

Increased cognitive problem reporting after information about chemotherapy-induced cognitive decline: The moderating role of stigma consciousness.

PubMed

Jacobs, W; Das, E; Schagen, S B

2017-01-01

Information about treatment side effects can increase their occurrence; breast cancer (BC) patients showed increased cognitive problem reporting (CPR) and decreased memory performance after information about cognitive side effects. The current study extends previous research on adverse information effects (AIE) by investigating (a) risk factors, (b) underlying mechanisms and (c) an intervention to reduce AIE. In an online experiment, 175 female BC patients were randomly assigned to one of three conditions. In the two experimental groups, patients were informed about the possible occurrence of cognitive problems after chemotherapy with (intervention group) or without (experimental group) reassuring information that 'there are still patients who score well on memory tests'. In the control group, no reference to chemotherapy-related cognitive problems was made. Main dependent measure was CPR. Four moderating and five mediating processes were examined. CPR increased with higher levels of stigma consciousness in the two experimental groups, but not in the no-information control group. Merely informing patients about cognitive side effects may increase their occurrence, especially among individuals vulnerable to patient stereotypes. Adding reassuring information is not sufficient to reduce AIE.

EXERCISE IMPROVES SEXUAL FUNCTION IN WOMEN TAKING ANTIDEPRESSANTS: RESULTS FROM A RANDOMIZED CROSSOVER TRIAL

PubMed Central

Lorenz, Tierney Ahrold; Meston, Cindy May

2014-01-01

Background In laboratory studies, exercise immediately before sexual stimuli improved sexual arousal of women taking antidepressants [1]. We evaluated if exercise improves sexual desire, orgasm, and global sexual functioning in women experiencing antidepressant-induced sexual side effects. Methods Fifty-two women who were reporting antidepressant sexual side effects were followed for 3 weeks of sexual activity only. They were randomized to complete either three weeks of exercise immediately before sexual activity (3×/week) or 3 weeks of exercise separate from sexual activity (3×/week). At the end of the first exercise arm, participants crossed to the other. We measured sexual functioning, sexual satisfaction, depression, and physical health. Results Exercise immediately prior to sexual activity significantly improved sexual desire and, for women with sexual dysfunction at baseline, global sexual function. Scheduling regular sexual activity significantly improved orgasm function; exercise did not increase this benefit. Neither regular sexual activity nor exercise significantly changed sexual satisfaction. Conclusions Scheduling regular sexual activity and exercise may be an effective tool for the behavioral management of sexual side effects of antidepressants. PMID:24754044

Exercise improves sexual function in women taking antidepressants: results from a randomized crossover trial.

PubMed

Lorenz, Tierney Ahrold; Meston, Cindy May

2014-03-01

In laboratory studies, exercise immediately before sexual stimuli improved sexual arousal of women taking antidepressants [1]. We evaluated if exercise improves sexual desire, orgasm, and global sexual functioning in women experiencing antidepressant-induced sexual side effects. Fifty-two women who were reporting antidepressant sexual side effects were followed for 3 weeks of sexual activity only. They were randomized to complete either three weeks of exercise immediately before sexual activity (3×/week) or 3 weeks of exercise separate from sexual activity (3×/week). At the end of the first exercise arm, participants crossed to the other. We measured sexual functioning, sexual satisfaction, depression, and physical health. Exercise immediately prior to sexual activity significantly improved sexual desire and, for women with sexual dysfunction at baseline, global sexual function. Scheduling regular sexual activity significantly improved orgasm function; exercise did not increase this benefit. Neither regular sexual activity nor exercise significantly changed sexual satisfaction. Scheduling regular sexual activity and exercise may be an effective tool for the behavioral management of sexual side effects of antidepressants

Orthostatic side effects of clomipramine and moclobemide during treatment for depression.

PubMed

Stage, Kurt Bjerregaard Bjerregaard

2005-01-01

From a clinical point of view, orthostatic hypotension is a significant side effect during antidepressant treatment, particularly in the case of tricyclic antidepressants (TCAs). This prospective, randomized clinical trial evaluated the effects of clomipramine and moclobemide on orthostatic blood pressure during treatment for depression. One hundred and fifteen depressed inpatients, age up to 70 years, were randomized to treatment with either moclobemide (400 mg/day) or clomipramine (150 mg/day) after 1 week of placebo treatment. Orthostatic blood pressure was measured weekly over the 6-week study period. Clomipramine, but not moclobemide, caused a statistically significant fall in systolic (F = 9.37, P = 0.0037) and diastolic orthostatic blood pressure (F = 3.74, P = 0.0017). In the clomipramine-treated group of patients, we found no correlation between subjective complaints of orthostatic dizziness and the size of systolic orthostatic blood pressure. In conclusion, this study indicates that moclobemide does not induce orthostatic side effects, which is a significant problem in treatment with TCAs. However, the choice of antidepressants depends on other factors as well, e.g. the therapeutic efficacy.

Antinociceptive effect induced by a combination of opioid and neurotensin moieties vs. their hybrid peptide [Ile(9)]PK20 in an acute pain treatment in rodents.

PubMed

Kleczkowska, Patrycja; Hermans, Emmanuel; Kosson, Piotr; Kowalczyk, Agnieszka; Lesniak, Anna; Pawlik, Karolina; Bojnik, Engin; Benyhe, Sandor; Nowicka, Barbara; Bujalska-Zadrozny, Magdalena; Misicka, Aleksandra; Lipkowski, Andrzej W

2016-10-01

Hybrid compounds are suggested to be a more effective remedy for treatment of various diseases than combination therapy, since the attenuation or total disappearance of side effects, typically induced by a single moiety, can be observed. This is of great importance, especially when we consider problems resulting from the use of opioid analgesics. However, although it seems that such compounds can be valuable therapeutic tools, the lack of conviction among the public as to the appropriateness of their use still remains; therefore patients are commonly treated with polypharmacy. Thus, in the presented paper we show a comparison of the antinociceptive effect between a novel opioid-neurotensin chimera called [Ile(9)]PK20 and a mixture of its structural elements, delivered intrathecally and systemically. Additionally, motor coordination was assessed in the rotarod test. The results clearly indicate that spinal administration of the examined compounds, resulted in a long-lasting, dose- and time-dependent antinociceptive effect. Although the mixture of both pharmacophores was found to be more active than [Ile(9)]PK20, motor impairments surfaced as a side effect. This in turn illustrates the advantageous use of hybrid structures over drug cocktails. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of CO2 laser treatment on skin tissue.

PubMed

Baleg, Sana Mohammed Anayb; Bidin, Noriah; Suan, Lau Pik; Ahmad, Muhammad Fakarruddin Sidi; Krishnan, Ganesan; Johari, Abd Rahman; Hamid, Asma

2015-09-01

The aim of this study was to evaluate the effects of multiple pulses on the depth of injury caused by CO2 laser in an in vivo rat model. A 10 600-nm CO2 laser was applied to rat skin, with one side of the rat dorsal skin being exposed, leaving the other side as a control. All of the various laser pulses tested led to gradual loss of epidermal thickness as well as a dramatic increase in thermal damage depth. Collagen coagulation was most effective with ten pulses of CO2 laser, while the strength of irradiated skin tissue increased as the influence of the laser increased. Fundamental laser-skin interaction effects were studied using a CO2 laser. The photodamaged areas obtained from laser interaction were recorded via couple charge device video camera and analyzed via ImageJ software. Photodamage induced by CO2 laser is due to photothermal effects, which involve burning and vaporizing mechanisms to ablate the epidermis layer. The burning area literally expands and penetrates deep into the dermis layer, subsequently causing collagen coagulation. This fundamental study shows in detail the effect of CO2 laser interaction with skin. The CO2 attributed severe burning, producing deep coagulation, and induced strength to treated skin. © 2015 Wiley Periodicals, Inc.

Chemotherapy-Induced Peripheral Neuropathy: A Current Review

PubMed Central

Staff, Nathan P.; Grisold, Anna; Grisold, Wolfgang; Windebank, Anthony J.

2017-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. Approximately 30–40% of patients treated with neurotoxic chemotherapy will develop CIPN and there is considerable variability in its severity between patients. It is often sensory-predominant with pain and can lead to long-term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents. PMID:28486769

Side effects in preventive maintenance therapy with neuroleptics with special emphasis on tardive dyskinesia.

PubMed

Logothetis, J; Paraschos, A; Frangos, E

1981-01-01

Neuroleptics induce hypersensitivity reactions, and toxic, systemic and extrapyramidal manifestations. The latter mainly include acute dystonic reactions, other early dyskinesias, akathisia, parkinsonism and TD. These drugs have been implicated for DA antagonism exerted by an adenylate cyclase inhibition. Prolonged blockade of DA receptors is considered as the motivation for a counterbalancing mechanism inducing the DA supersensitivity from which TD results. Recent reports suggest cholinergic and GABA ergic insufficiency as secondary participants. The increasing frequency of TD calls for prevention by modifying treatment practices and searching for effective measures to combat the symptoms.

Conditioned Side Effects Induced by Cancer Chemotherapy: Prevention Through Behavioral Treatment.

ERIC Educational Resources Information Center

Burish, Thomas G.; And Others

1987-01-01

Studied cancer patients (N=24) in order to determine whether conditioned nausea and vomiting could be delayed or prevented. Indicated that patients receiving progressive muscle relaxation training and guided imagery had significantly less nausea and vomiting and significanty lower blood pressures, pulse rates, and dysphoria, especially anxiety,…

Clozapine-Induced Febrile Neutropenia and Cellulitis.

PubMed

Yaylaci, Selcuk; Yilmaz, Emine Ulku; Guclu, Ertugrul; Kumsar, Neslihan Akkisi; Tamer, Ali; Karabay, Oguz

2014-03-01

Clozapine is one of the atypical antipsychotics and is frequently prescribed to patients with treatment-resistant schizophrenia. Agranulocytosis is a major side effect that may lead to death, which limits its use. This is a case report of a patient that developed febrile neutropenia and cellulitis after treatment with clozapine for 20 weeks.

[Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

PubMed

Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

2009-08-18

It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a potentially harmful or a useful event in radiotherapy. The elevation of damage to tumor cells not directly hit by radiation or the initiation of tumor cell differentiation may increase the therapeutic ratio. If, however, molecular species secreted by irradiated tumor cells in vivo damage neighboring normal cells (epithelial and endothelial cells, fibroblasts, or lymphocytes), the bystander effect would be harmful and could lead to increased side effects in normal tissue. This is especially important in modern radiotherapy, as 3D conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) are aimed at diminishing the radiation dose in normal tissues. Recent in vivo studies on animals indicate that bystander effects may appear in organs and tissues remote from the irradiated field and the extension of tissue damage seems to be tissue-type dependent. However, recent experimental results indicate that non-irradiated cells that are neighbors of irradiated cells may diminish radiation damage in the radiation-focused cells. Less is known about the bystander effect during fractionated irradiation. Thus the clinical implications of the bystander effect and its possible modification for radiotherapeutic usefulness is still under debate.

Contraceptive effect and potential side-effects of deslorelin acetate implants in rats (Rattus norvegicus): Preliminary observations

PubMed Central

Grosset, Claire; Peters, Stijn; Peron, Franck; Figuéra, Joëlle; Navarro, Christelle

2012-01-01

During the last ten years, numerous species have been treated with deslorelin implants to induce contraception. The aims of the study were 1) to assess contraceptive efficacy of 4.7 mg subcutaneous deslorelin implants in rats, 2) to determine the latency of contraceptive effect, and 3) to determine potential side effects. Three experimental females were implanted and their estrous cycle was studied by vaginal smear. Two weeks after implantation, a male whose fertility was previously assessed with a control female, was introduced into their cage. No female conceived during the 4 mo following implantation. Additionally, 38 pet rats were recruited from clients in practice to test for potential side effects, including 6 males and 32 females with a mean age of 14 mo. Local reaction and transient weight gain during the first 2 wk, as well as behavioral changes were recorded. According to this pilot study, deslorelin implant could be used as a contraceptive method in female rats. The latency period is about 2 wk. Nevertheless, it might be possible to refine the treatment further using hormonal measurements. The duration of contraceptive effect is to be determined in an upcoming study. PMID:23277700

Potentiation of transient receptor potential V1 functions by the activation of metabotropic 5-HT receptors in rat primary sensory neurons

PubMed Central

Ohta, Toshio; Ikemi, Yuki; Murakami, Matsuka; Imagawa, Toshiaki; Otsuguro, Ken-ichi; Ito, Shigeo

2006-01-01

5-Hydroxytryptamine (5-HT) is one of the major chemical mediators released in injured and inflamed tissue and is capable of inducing hyperalgesia in vivo. However, the cellular mechanisms of 5-HT-induced hyperalgesia remain unclear. Transient receptor potential V1 (TRPV1) plays a pivotal role in nociceptive receptors. In the present study, we determined whether 5-HT changes TRPV1 functions in cultured dorsal root ganglion (DRG) neurons isolated from neonatal rats, using Ca2+ imaging and whole-cell patch-clamp techniques. In more than 70% of DRG neurons, 5-HT potentiated the increases of [Ca2+]i induced by capsaicin, protons and noxious heat. Capsaicin-induced current and depolarizing responses, and proton-induced currents were also augmented by 5-HT. RT-PCR analysis revealed the expression of 5-HT2A and 5-HT7 receptors in rat DRG neurons. Agonists for 5-HT2A and 5-HT7 receptors mimicked the potentiating effect of 5-HT, and their antagonists decreased it. In DRG ipsilateral to the complete Freund's adjuvant-injected inflammation side, expression levels of 5-HT2A and 5-HT7 mRNAs increased, and the potentiating effect of 5-HT was more prominent than in the contralateral control side. These results suggest that the PKC- and PKA-mediated signalling pathways are involved in the potentiating effect of 5-HT on TRPV1 functions through the activation of 5-HT2A and 5-HT7 receptors, respectively. Under inflammatory conditions, the increases of the biosynthesis of these 5-HT receptors may lead to further potentiation of TRPV1 functions, resulting in the generation of inflammatory hyperalgesia in vivo. PMID:16901936

Slope effects on the fluid dynamics of a fire spreading across a fuel bed: PIV measurements and OH* chemiluminescence imaging

NASA Astrophysics Data System (ADS)

Morandini, F.; Silvani, X.; Honoré, D.; Boutin, G.; Susset, A.; Vernet, R.

2014-08-01

Slope is among the most influencing factor affecting the spread of wildfires. A contribution to the understanding of the fluid dynamics of a fire spreading in these terrain conditions is provided in the present paper. Coupled optical diagnostics are used to study the slope effects on the flow induced by a fire at laboratory scale. Optical diagnostics consist of particle image velocimetry, for investigating the 2D (vertical) velocity field of the reacting flow and chemiluminescence imaging, for visualizing the region of spontaneous emission of OH radical occurring during gaseous combustion processes. The coupling of these two techniques allows locating accurately the contour of the reaction zone within the computed velocity field. The series of experiments are performed across a bed of vegetative fuel, under both no-slope and 30° upslope conditions. The increase in the rate of fire spread with increasing slope is attributed to a significant change in fluid dynamics surrounding the flame. For horizontal fire spread, flame fronts exhibit quasi-vertical plume resulting in the buoyancy forces generated by the fire. These buoyancy effects induce an influx of ambient fresh air which is entrained laterally into the fire, equitably from both sides. For upward flame spread, the induced flow is strongly influenced by air entrainment on the burnt side of the fire and fire plume is tilted toward unburned vegetation. A particular attention is paid to the induced air flow ahead of the spreading flame. With increasing the slope angle beyond a threshold, highly dangerous conditions arise because this configuration induces wind blows away from the fire rather than toward it, suggesting the presence of convective heat transfers ahead of the fire front.

Mechanism of drug-induced gingival overgrowth revisited: a unifying hypothesis

PubMed Central

Brown, RS; Arany, PR

2015-01-01

Drug-induced gingival overgrowth (DIGO) is a disfiguring side effect of anti-convulsants, calcineurin inhibitors, and calcium channel blocking agents. A unifying hypothesis has been constructed which begins with cation flux inhibition induced by all three of these drug categories. Decreased cation influx of folic acid active transport within gingival fibroblasts leads to decreased cellular folate uptake, which in turn leads to changes in matrix metalloproteinases metabolism and the failure to activate collagenase. Decreased availability of activated collagenase results in decreased degradation of accumulated connective tissue which presents as DIGO. Studies supporting this hypothesis are discussed. PMID:24893951

Rising Trend of Use of Antidepressants Induced Non- Puerperal Lactation: A Case Report.

PubMed

Kukreti, Prerna; Ali, Wazid; Jiloha, R C

2016-06-01

Non puerperal lactation or galactorrhea is a well known side effect of antipsychotic drugs but has been infrequently described with the use of antidepressants. In past few decades, there have been emerging trend of isolated case reports of selective serotonin reuptake inhibitors induced non puerperal lactation. We report a case of non puerperal lactation following usage of second generation tricyclic antidepressant, nortriptyline and resolution on withdrawing the drug. Literature review has been done for antidepressant induced galactorrhea to understand the current trends, putative mechanism as different from one implicated for antipsychotics and its clinical utility.

Effects of dendritic cell-activated and cytokine-induced killer cell therapy on 22 children with acute myeloid leukemia after chemotherapy.

PubMed

Bai, Yan; Zheng, Jin-e; Wang, Nan; Cai, He-hua; Zhai, Li-na; Wu, Yao-hui; Wang, Fang; Jin, Run-ming; Zhou, Dong-feng

2015-10-01

The efficiency of dendritic cell-activated and cytokine-induced killer cell (DC-CIK) therapy on children with acute myeloid leukemia (AML) after chemotherapy was investigated. Mononuclear cells were collected from children achieving complete remission after chemotherapy, cultured in vitro and transfused back into the same patient. Interleukin-2 (IL-2) was injected subcutaneously every other day 10 times at the dose of 1 × 10(6) units. Peripheral blood lymphocyte subsets and minimal residual disease (MRD) were detected by flow cytometry. Function of bone marrow was monitored by methods of morphology, immunology, cytogenetics and molecular biology. The side effects were also observed during the treatment. The average follow-up period for all the 22 patients was 71 months and relapse occurred in two AML patients (9.1%). The percentage of CD3(+)/CD8(+) cells in peripheral blood of 15 patients at the 3rd month after DC-CIK treatment (36.73% ± 12.51%) was dramatically higher than that before treatment (29.20% ± 8.34%, P < 0.05). The MRD rate was >0.1% in 5 patients before the treatment, and became lower than 0.1% 3 months after the treatment. During the transfusion of DC-CIK, side effects including fever, chills and hives appeared in 7 out of 22 (31.82%) cases but disappeared quickly after symptomatic treatments. There were no changes in electrocardiography and liver-renal functions after the treatment. MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects.

Icariin, a flavonoid with anti-cancer effects, alleviated paclitaxel-induced neuropathic pain in a SIRT1-dependent manner.

PubMed

Gui, Yulong; Zhang, Jie; Chen, Liang; Duan, Shunyuan; Tang, Jing; Xu, Wei; Li, Aiyuan

2018-01-01

Background One of the most common side effects of paclitaxel was dosage-dependently painful neuropathy. Various reports indicated that spinal neuroinflammation was involved in paclitaxel-induced neuropathic pain. This study investigated the effect of icariin on paclitaxel-induced neuroinflammation and peripheral neuropathy in rats. Methods Two parts were included in this study. In part one, the effect of icariin on paclitaxel-induced neuropathic pain was investigated. Mechanical thresholds were measured as primary outcomes. Production of proinflammatory factors (tumor necrosis factor-α, interleukin-1 β, and interleukin-6), activation of nuclear factor-κB (NF-κB(p65)) signal, and activation of astrocytes were detected as secondary outcomes. Spinal Sirtuin 1 (SIRT1) expression, H4 acetylation, and NAD + content were measured to investigate the effect of icariin on spinal SIRT1 signal pathway. In part two, the role of SIRT1 signal on icariin-induced effect in rats was investigated, and EX527, a SIRT1 inhibitor, was employed. Results The results showed paclitaxel treatment induced significant decrease in mechanical thresholds. Paclitaxel treatment also induced NF-κB(p65) activation and upregulation of proinflammatory factors (TNF-α, IL-1β, and IL-6). Paclitaxel also induced astrocyte activation in the spinal cord. However, 100 mg/kg icariin treatment significantly alleviated paclitaxel-induced mechanical allodynia and spinal neuroinflammation. Furthermore, icariin treatment dosage-dependently reversed paclitaxel-induced SIRT1 downregulation and H4 acetylation. EX527, a selective SIRT1 inhibitor, completely reversed icariin-induced anti-neuroinflammation and anti-allodynia effects in paclitaxel-induced neuropathic pain rats. Conclusions This meant that spinal SIRT1 activation was involved in icariin-induced effects in paclitaxel-induced neuropathic pain rats. Icariin could be a potential agent for the treatment of paclitaxel-induced neuropathic pain.

Carbamylated monomeric allergoids as a therapeutic option for sublingual immunotherapy of dust mite- and grass pollen-induced allergic rhinoconjunctivitis: a systematic review of published trials with a meta-analysis of treatment using Lais® tablets.

PubMed

Mösges, R; Ritter, B; Kayoko, G; Allekotte, S

2010-10-01

Lais® allergoid tablets contain allergens that are modified by carbamylation. Due to their modified chemical structure, they are suitable for sublingual immunotherapy (SLIT) (13, 16, 17, 24). Based on their small molecule size of 12 to 40 kDa, they can be easily absorbed via the oral mucosa (1). In this review, we studied the efficacy of SLIT with carbamylated monomeric allergoid tablets in the treatment of grass pollen- and dust mite-induced allergic rhinoconjunctivitis on the basis of symptom and medication score improvements. Following a selective internet and databank search, six trials-some placebo-controlled-regarding the treatment of grass pollen- (n = 266) and dust mite-induced (n = 241) allergic rhinoconjunctivitis were used to draw conclusions regarding the clinical efficacy of allergoid tablets. The primary endpoints in these trials were decreases in the need for allergy medications and/or reductions in the occurrence of rhinoconjunctivitis symptoms. Data was recorded from patient diaries regarding their symptoms and medications used and conclusions were then drawn about the effectiveness and tolerabieity of Lais® tablets. The average improvement in symptom score in three trials of grass pollen allergy treatment was 34% in comparison to the placebo group. The treatment of dust mite-induced rhinoconjunctivitis produced an average symptom score improvement of 22% compared to the placebo or control groups. The intake of symptomatic rescue medication during allergoid tablet therapy declined. Treatment of grass pollen allergies and dust mite-induced rhinoconjunctivitis showed an average medication score improvement of 49% and 24%, respectively. Few side effects were documented in the trials and predominantly local effects were observed. Severe systemic side effects did not occur. On the basis of the trial results summarized in this review, we suggest that SLIT using Lais® sublingual tablets is an effective and well-tolerated form of treatment.

Sex Hormones Protect Against Amyloid-β Induced Oxidative Stress in the Choroid Plexus Cell Line Z310.

PubMed

Costa, A R; Marcelino, H; Gonçalves, I; Quintela, T; Tomás, J; Duarte, A C; Fonseca, A M; Santos, C R A

2016-09-01

The choroid plexus (CP) epithelium is a unique structure in the brain that forms an interface between the peripheral blood on the basal side and the cerebrospinal fluid (CSF) on the apical side. It is a relevant source of many polypeptides secreted to the CSF with neuroprotective functions and also participates in the elimination and detoxification of brain metabolites, such as β-amyloid (Aβ) removal from the CSF through transporter-mediated influx. The CP is also a target tissue for sex hormones (SHs) that have recognised neuroprotective effects against a variety of insults, including Aβ toxicity and oxidative stress in the central nervous system. The present study aimed to understand how SHs modulate Aβ-induced oxidative stress in a CP cell line (Z310 cell line) by analysing the effects of Aβ1-42 on oxidative stress, mitochondrial function and apoptosis, as well as by assessing how 17β-oestradiol (E2 ) and 5α-dihydrotestosterone (DHT) modulated these effects and the cellular uptake of Aβ1-42 by CP cells. Our findings show that E2 and DHT treatment reduce Aβ1-42 -induced oxidative stress and the internalisation of Aβ1-42 by CP epithelial cells, highlighting the importance of considering the background of SHs and therefore sex-related differences in Aβ metabolism and clearance by CP cells. © 2016 British Society for Neuroendocrinology.

Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): a systematic review.

PubMed

Schloss, Janet M; Colosimo, Maree; Airey, Caroline; Masci, Paul P; Linnane, Anthony W; Vitetta, Luis

2013-12-01

Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. To determine the potential use of nutraceuticals i.e. vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as adjuvants in cancer treatments a systematic literature review was conducted. Revised clinical studies comprised of randomized clinical trials that investigated the anti-CIPN effect of nutraceuticals as the adjuvant intervention in patients administered chemotherapy. Twenty-four studies were assessed on methodological quality and limitations identified. Studies were mixed in their recommendations for nutraceuticals. Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. The standard of care for CIPN includes dose reduction and/or discontinuation of chemotherapy treatment. The management of CIPN remains an important challenge and future studies are warranted before recommendations for the use of supplements can be made. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Molecular insight into the counteraction of trehalose on urea-induced protein denaturation using molecular dynamics simulation.

PubMed

Zhang, Na; Liu, Fu-Feng; Dong, Xiao-Yan; Sun, Yan

2012-06-21

Considerable experimental evidence indicates that trehalose can counteract the denaturing effects of urea on proteins. However, its molecular mechanism remains unknown due to the limitations of current experimental techniques. Herein, molecular dynamics simulations were performed to investigate the counteracting effects of trehalose against urea-induced denaturation of chymotrypsin inhibitor 2. The simulations indicate that the protein unfolds in 8 mol/L urea, but at the same condition the protein retains its native structure in the ternary solution of 8 mol/L urea and 1 mol/L trehalose. It is confirmed that the preferential exclusion of trehalose from the protein surface is the origin of its counteracting effects. It is found that trehalose binds urea via hydrogen bonds, so urea molecules are also expelled from the protein surface along with the preferential exclusion of trehalose. The exclusion of urea from the protein surface leads to the alleviation of the Lennard-Jones interactions between urea and the hydrophobic side chains of the protein in the ternary solution. In contrast, the electrostatic interactions between urea and the protein change little in the presence of trehalose because the decrease in the electrostatic interactions between urea and the protein backbone is canceled by the increase in the electrostatic interactions between urea and the charged side chains of the protein. The results have provided molecular explanations for the counteraction of urea-induced protein denaturation by trehalose.

Mitochondrial ADP/ATP exchange inhibition: a novel off-target mechanism underlying ibipinabant-induced myotoxicity.

PubMed

Schirris, Tom J J; Ritschel, Tina; Herma Renkema, G; Willems, Peter H G M; Smeitink, Jan A M; Russel, Frans G M

2015-09-29

Cannabinoid receptor 1 (CB1R) antagonists appear to be promising drugs for the treatment of obesity, however, serious side effects have hampered their clinical application. Rimonabant, the first in class CB1R antagonist, was withdrawn from the market because of psychiatric side effects. This has led to the search for more peripherally restricted CB1R antagonists, one of which is ibipinabant. However, this 3,4-diarylpyrazoline derivative showed muscle toxicity in a pre-clinical dog study with mitochondrial dysfunction. Here, we studied the molecular mechanism by which ibipinabant induces mitochondrial toxicity. We observed a strong cytotoxic potency of ibipinabant in C2C12 myoblasts. Functional characterization of mitochondria revealed increased cellular reactive oxygen species generation and a decreased ATP production capacity, without effects on the catalytic activities of mitochondrial enzyme complexes I-V or the complex specific-driven oxygen consumption. Using in silico off-target prediction modelling, combined with in vitro validation in isolated mitochondria and mitoplasts, we identified adenine nucleotide translocase (ANT)-dependent mitochondrial ADP/ATP exchange as a novel molecular mechanism underlying ibipinabant-induced toxicity. Minor structural modification of ibipinabant could abolish ANT inhibition leading to a decreased cytotoxic potency, as observed with the ibipinabant derivative CB23. Our results will be instrumental in the development of new types of safer CB1R antagonists.

Long Duration Exposure Facility (LDEF) preliminary findings: LEO space effects on the space plasma-voltage drainage experiment

NASA Technical Reports Server (NTRS)

Blakkolb, Brian K.; Yaung, James Y.; Henderson, Kelly A.; Taylor, William W.; Ryan, Lorraine E.

1992-01-01

The Space Plasma-High Voltage Drainage Experiment (SP-HVDE) provided a unique opportunity to study long term space environmental effects on materials because it was comprised of two identical experimental trays; one tray located on the ram facing side (D-10), and the other on the wake facing side (B-4) of the LDEF. This configuration allows for the comparison of identical materials exposed to two distinctly different environments. The purpose of this work is to document an assessment of the effects of five and three quarters years of low Earth orbital space exposure on materials comprising the SP-HVDE (experiment no. A0054). The findings of the materials investigation reported focus on atomic oxygen effects, micrometeor and debris impact site documentation, thermal property measurements, and environmentally induced contamination.

Use of side-chain for rational design of n-type diketopyrrolopyrrole-based conjugated polymers: what did we find out?

PubMed

Kanimozhi, Catherine; Yaacobi-Gross, Nir; Burnett, Edmund K; Briseno, Alejandro L; Anthopoulos, Thomas D; Salzner, Ulrike; Patil, Satish

2014-08-28

The primary role of substituted side chains in organic semiconductors is to increase their solubility in common organic solvents. In the recent past, many literature reports have suggested that the side chains play a critical role in molecular packing and strongly impact the charge transport properties of conjugated polymers. In this work, we have investigated the influence of side-chains on the charge transport behavior of a novel class of diketopyrrolopyrrole (DPP) based alternating copolymers. To investigate the role of side-chains, we prepared four diketopyrrolopyrrole-diketopyrrolopyrrole (DPP-DPP) conjugated polymers with varied side-chains and carried out a systematic study of thin film microstructure and charge transport properties in polymer thin-film transistors (PTFTs). Combining results obtained from grazing incidence X-ray diffraction (GIXD) and charge transport properties in PTFTs, we conclude side-chains have a strong influence on molecular packing, thin film microstructure, and the charge carrier mobility of DPP-DPP copolymers. However, the influence of side-chains on optical properties was moderate. The preferential "edge-on" packing and dominant n-channel behavior with exceptionally high field-effect electron mobility values of >1 cm(2) V(-1) s(-1) were observed by incorporating hydrophilic (triethylene glycol) and hydrophobic side-chains of alternate DPP units. In contrast, moderate electron and hole mobilities were observed by incorporation of branched hydrophobic side-chains. This work clearly demonstrates that the subtle balance between hydrophobicity and hydrophilicity induced by side-chains is a powerful strategy to alter the molecular packing and improve the ambipolar charge transport properties in DPP-DPP based conjugated polymers. Theoretical analysis supports the conclusion that the side-chains influence polymer properties through morphology changes, as there is no effect on the electronic properties in the gas phase. The exceptional electron mobility is at least partially a result of the strong intramolecular conjugation of the donor and acceptor as evidenced by the unusually wide conduction band of the polymer.

Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) as a Target for Concurrent Management of Diabetes and Obesity-Related Cancer.

PubMed

Wang, Qingqing; Imam, Mustapha Umar; Yida, Zhang; Wang, Fudi

2017-01-01

Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor superfamily of ligand-inducible transcription factors that regulate adipogenesis, lipid metabolism, cell proliferation, inflammation and insulin sensitization. Abnormalities in PPARγ signaling have been associated with obesity, diabetes and cancer. The use of agonists to manage these diseases has been limited by their side effects. Accordingly, dual or pan agonists targeting the PPARα or PPARα and PPARδ, respectively, in addition to the PPARγ have been developed to overcome these side effects. This review details the shared PPARγ-dependent mechanisms between obesity-related cancers and diabetes and their potential therapeutic values. We performed a systematic literature search through pubmed, Scopus and google scholar for articles on PPARγ-dependent signaling in diabetes or cancer. There is growing co-occurrence of obesity-related cancers and diabetes, necessitating the use of effective therapies with the least amount of side effects for concurrent management of these diseases, by targeting potentially shared PPARγ-dependent mechanisms including abnormalities of the wnt/β-catenin, lysosomal acid lipase, inflammatory and cell cycle pathways, and the plasminogen activator system. Taking advantage of the multiple docking sites of the PPARγ and the pleiotropic nature of its signaling, structure-activity relationship and molecular docking studies have provided insights into designer PPARγ agonists or dual PPARα/γ agonists that modulate PPARγ signaling and negate side effects of full PPARγ agonists. Effective therapies, possibly devoid of side effects, for concurrent management of obesity-related cancers and diabetes can be developed through diligent structure-activity and molecular docking studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via σ1 receptor activation: comparison with the effects of dextromethorphan

PubMed Central

Shin, Eun-Joo; Nah, Seung-Yeol; Kim, Won-Ki; Ko, Kwang Ho; Jhoo, Wang-Kee; Lim, Yong-Kwang; Cha, Joo Young; Chen, Chieh-Fu; Kim, Hyoung-Chun

2005-01-01

In a previous study, we demonstrated that a dextromethorphan analog, dimemorfan, has neuroprotective effects. Dextromethorphan and dimemorfan are high-affinity ligands at σ1 receptors. Dextromethorphan has moderate affinities for phencyclidine sites, while dimemorfan has very low affinities for such sites, suggesting that these sites are not essential for the anticonvulsant actions of dimemorfan. Kainate (KA) administration (10 mg kg−1, i.p.) produced robust convulsions lasting 4–6 h in rats. Pre-treatment with dimemorfan (12 or 24 mg kg−1) reduced seizures in a dose-dependent manner. Dimemorfan pre-treatment also attenuated the KA-induced increases in c-fos/c-jun expression, activator protein (AP)-1 DNA-binding activity, and loss of cells in the CA1 and CA3 fields of the hippocampus. These effects of dimemorfan were comparable to those of dextromethorphan. The anticonvulsant action of dextromethorphan or dimemorfan was significantly counteracted by a selective σ1 receptor antagonist BD 1047, suggesting that the anticonvulsant action of dextromethorphan or dimemorfan is, at least in part, related to σ1 receptor-activated modulation of AP-1 transcription factors. We asked whether dimemorfan produces the behavioral side effects seen with dextromethorphan or dextrorphan (a phencyclidine-like metabolite of dextromethorphan). Conditioned place preference and circling behaviors were significantly increased in mice treated with phencyclidine, dextrorphan or dextromethorphan, while mice treated with dimemorfan showed no behavioral side effects. Our results suggest that dimemorfan is equipotent to dextromethorphan in preventing KA-induced seizures, while it may lack behavioral effects, such as psychotomimetic reactions. PMID:15723099

Effects of CDP-choline on striatal dopamine level and behavior in rats.

PubMed

Shibuya, M; Kageyama, N; Taniguchi, T; Hidaka, H; Fujiwara, M

1981-02-01

To further assess the effects of CDP (cytidine diphosphate)-choline on Parkinsonian symptoms, striatal dopamine (DA) was measured fluorometrically in rats after injection of CDP-choline. CDP-choline (300 mg/kg, i.p.) increased the DA content in the striatum (p less than 0.05) one hour after injection. The behavioral effect of CDP-choline was then tested in rats in which the unilateral nigro-striatal DA neurons had degenerated following an intranigral injection of 6-hydroxydopamine (6-OHDA). CDP-choline alone did not produce behavioral changes in these rats. However, pretreatment with a single dose of CDP-choline (900 mg/kg, i.p.) suppressed both the apomorphine-induced contralateral and the d-amphetamine-induced ipsilateral circling. The same dose of CDP-choline suppressed the number of treadmill revolutions in mice. On the other hand, a 7-day consecutive treatment with 300 mg/kg of CDP-choline enhanced the apomorphine-induced contralateral circling (by 42%, p less than 0.05). The same treatment with CDP-choline raised the striatal DA content by 29% (p less than 0.05) on the intact side, but not on the 6-OHDA injected side. These results indicate that CDP-choline has either a direct nor an indirect DA agonistic effect. The increase in DA content, decrease in locomotion and enhancement of the effect of apomorphine can be explained on the hypothesis that CDP-choline may act as an antagonist on the DA neurons and receptors. The validity of this apparently paradoxical use of CDP-choline with antagonistic effect on DA neurons in the treatment of Parkinson's disease is discussed.

Side-chain-side-chain interactions and stability of the helical state

NASA Astrophysics Data System (ADS)

Zangi, Ronen

2014-01-01

Understanding the driving forces that lead to the stability of the secondary motifs found in proteins, namely α-helix and β-sheet, is a major goal in structural biology. The thermodynamic stability of these repetitive units is a result of a delicate balance between many factors, which in addition to the peptide chain involves also the solvent. Despite the fact that the backbones of all amino acids are the same (except of that of proline), there are large differences in the propensity of the different amino acids to promote the helical structure. In this paper, we investigate by explicit-solvent molecular dynamics simulations the role of the side chains (modeled as coarse-grained single sites) in stabilizing α helices in an aqueous solution. Our model systems include four (six-mer-nine-mer) peptide lengths in which the magnitude of the effective attraction between the side chains is systematically increased. We find that these interactions between the side chains can induce (for the nine-mer almost completely) a transition from a coil to a helical state. This transition is found to be characterized by three states in which the intermediate state is a partially folded α-helical conformation. In the absence of any interactions between the side chains the free energy change for helix formation has a small positive value indicating that favorable contributions from the side chains are necessary to stabilize the helical conformation. Thus, the helix-coil transition is controlled by the effective potentials between the side-chain residues and the magnitude of the required attraction per residue, which is on the order of the thermal energy, reduces with the length of the peptide. Surprisingly, the plots of the population of the helical state (or the change in the free energy for helix formation) as a function of the total effective interactions between the side chains in the helical state for all peptide lengths fall on the same curve.

Effects of Cynodon dactylon on Stress-Induced Infertility in Male Rats

PubMed Central

Chidrawar, VR; Chitme, HR; Patel, KN; Patel, NJ; Racharla, VR; Dhoraji, NC; Vadalia, KR

2011-01-01

Cynodon dactylon (Family: Poaceae) is known to be a tackler in Indian mythology and is offered to Lord Ganesha. It is found everywhere, even on waste land, road side, dry places, and spreads vigorously on cultivated ground. This study was carried out with an objective to test if the constituents of this plant are useful in coping stress-induced sexual In this study, we considered immobilization stress to induce male infertility and the effect of C. dactylon in restoration of the dysfunction was evaluated by considering sexual behavioral observations, sexual performance, fructose content of the seminal vesicles, epididymal sperm concentration and histopathological examinations as parameters. Treatment of rats under stress with methanolic extract of C. dactylon has shown a promising effect in overcoming stress-induced sexual dysfunction, sexual performance, fructose content, sperm concentration and its effect on accessory sexual organs and body weight. We conclude that active constituents of C. dactylon present in methanolic extract have a potent aphrodisiac and male fertility activity. PMID:21607051

Radioprotective effects of delphinidin on normal human lung cells against proton beam exposure

PubMed Central

Kim, Hyun Mi; Kim, Suk Hee

2018-01-01

BACKGROUND/OBJECTIVES Exposure of the normal lung tissue around the cancerous tumor during radiotherapy causes serious side effects such as pneumonitis and pulmonary fibrosis. Radioprotectors used during cancer radiotherapy could protect the patient from side effects induced by radiation injury of the normal tissue. Delphinidin has strong antioxidant properties, and it works as the driving force of a radioprotective effect by scavenging radiation-induced reactive oxygen species (ROS). However, no studies have been conducted on the radioprotective effect of delphinidin against high linear energy transfer radiation. Therefore, this study was undertaken to evaluate the radioprotective effects of delphinidin on human lung cells against a proton beam. MATERIALS/METHODS Normal human lung cells (HEL 299 cells) were used for in vitro experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay assessed the cytotoxicity of delphinidin and cell viability. The expression of radiation induced cellular ROS was measured by the 2′-7′-dicholordihydrofluorescein diacetate assay. Superoxide dismutase activity assay and catalase activity assay were used for evaluating the activity of corresponding enzymes. In addition, radioprotective effects on DNA damage-induced cellular apoptosis were evaluated by Western blot assay. RESULTS Experimental analysis, including cell survival assay, MTT assay, and Western blot assay, revealed the radioprotective effects of delphinidin. These include restoring the activities of antioxidant enzymes of damaged cells, increase in the levels of pro-survival protein, and decrease of pro-apoptosis proteins. The results from different experiments were compatible with each to provide a substantial conclusion. CONCLUSION Low concentration (2.5 µM/mL) of delphinidin administration prior to radiation exposure was radioprotective against a low dose of proton beam exposure. Hence, delphinidin is a promising shielding agent against radiation, protecting the normal tissues around a cancerous tumor, which are unintentionally exposed to low doses of radiation during proton therapy. PMID:29399295

Opioid-Induced Bowel Dysfunction

PubMed Central

Cheng, Vivian; Lembo, Anthony

2013-01-01

Opioid-induced bowel dysfunction (OIBD) is a potentially debilitating side effect of chronic opioid use. It refers to a collection of primarily gastrointestinal motility disorders induced by opioids, of which opioid-induced constipation (OIC) is the most common. Management of OIBD is difficult, and affected patients will often limit their opioid intake at the expense of experiencing more pain, to reduce the negative impact of OIBD on their quality of life. Effective pharmacologic therapy for OIC is considered an unmet need and several agents have recently been given priority review and approval for OIC. Furthermore, multiple agents currently in development show promise in treating OIC without significant impact on analgesia or precipitation of withdrawal symptoms. The approval and availability of such medications would represent a significant improvement in the management of OIC and OIBD in patients with chronic pain. PMID:23900996

PROTECTIVE EFFECT OF IRIS GERMANICA L. IN Β-AMYLOID-INDUCED ANIMAL MODEL OF ALZHEIMER'S DISEASE.

PubMed

Borhani, Mona; Sharifzadeh, Mohammad; Farzaei, Mohammad Hosein; Narimani, Zahra; Sabbaghziarani, Fatemeh; Gholami, Mahdi; Rahimi, Roja

2017-01-01

Alzheimer's disease (AD) is the most common cause of dementia that is an irretrievable chronic neurodegenerative disease. In the current study, we have examined the therapeutic effects of Iris germanica extract on Amyloid β (Aβ) induced memory impairment. Wistar rats were divided into five groups of 8 per each. Groups were as followed: control group which were normal rats without induction of AD, Aβ group which received Aβ (50 ng/side), iris 100 group which received Aβ + Iris (100 mg/kg), iris 200 group which received Aβ + Iris (200 mg/kg), and iris 400 group which received Aβ + Iris (400 mg/kg). AD was established by intrahippocampal injection of 50 ng/μl/side Aβ1-42. The day after surgery, animals in treatment groups received different doses of the aqueous extract of Iris by gavage for 30 days. Morris water maze test (MWM) was performed to assess the effects of I. germanica on learning and memory of rats with Aβ induced AD. Data from MWM tests, including escape latency and traveled distance, demonstrated that I. germanica extract could markedly improve spatial memory in comparison to control. Moreover, the plant had a significantly better effect on the performance of AD rats in the probe test. I. germanica extract can successfully reverse spatial learning dysfunction in an experimental model of AD. Further neuro psyco-pharmacological studies are mandatory to reveal the mechanism of action of this natural remedy in the management of AD symptoms.

Synergistic anticancer activity of curcumin and bleomycin: an in vitro study using human malignant testicular germ cells.

PubMed

Cort, Aysegul; Timur, Mujgan; Ozdemir, Evrim; Kucuksayan, Ertan; Ozben, Tomris

2012-06-01

Testicular cancer is the most common cancer among young men of reproductive age. Bleomycin is a frequently used drug for the treatment of several malignancies and is part of the chemotherapy protocols used for testicular cancer; however, side-effects are common. Bleomycin causes an increase in oxidative stress which has been shown to induce apoptosis in cancer cells. Curcumin (diferuloylmethane), an active component of the spice turmeric, has been demonstrated to induce apoptosis in a number of malignancies. However, to date no study has been carried out to elucidate its anticancer activity and interaction with bleomycin in testicular cancer cells. In this study, we investigated and compared the effects of curcumin, bleomycin and hydrogen peroxide (H2O2) on apoptotic signaling pathways. Curcumin (20 µM), bleomycin (400 µg/ml) and H2O2 (400 µM) incubation for 24 h decreased the viability of NTera-2 cells, and increased caspase-3, -8 and -9 activities, Bax and cytoplasmic cytochrome c levels and decreased Bcl-2 levels. The concurrent use of curcumin with bleomycin induced caspase-3, -8 and -9 activities to a greater extent in NTera-2 cells than the use of each drug alone. Our observations suggest that the effects of curcumin and bleomycin on apoptotic signaling pathways are synergistic. Therefore, we propose to use curcumin together with bleomycin to decrease its therapeutic dose and, therefore, its side-effects.

FX-87 performance measurements: data-flow implementation. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammel, R.T.; Gifford, D.K.

1988-11-01

This report documents a series of experiments performed to explore the thesis that the FX-87 effect system permits a compiler to schedule imperative programs (i.e., programs that may contain side-effects) for execution on a parallel computer. The authors analyze how much the FX-87 static effect system can improve the execution times of five benchmark programs on a parallel graph interpreter. Three of their benchmark programs do not use side-effects (factorial, fibonacci, and polynomial division) and thus did not have any effect-induced constraints. Their FX-87 performance was comparable to their performance in a purely functional language. Two of the benchmark programsmore » use side effects (DNA sequence matching and Scheme interpretation) and the compiler was able to use effect information to reduce their execution times by factors of 1.7 to 5.4 when compared with sequential execution times. These results support the thesis that a static effect system is a powerful tool for compilation to multiprocessor computers. However, the graph interpreter we used was based on unrealistic assumptions, and thus our results may not accurately reflect the performance of a practical FX-87 implementation. The results also suggest that conventional loop analysis would complement the FX-87 effect system« less

Bimatoprost (0.03%)-induced accommodative spasm and pseudomyopia

PubMed Central

Padhy, Debananda; Rao, Aparna

2015-01-01

Bimatoprost is a prostaglandin analogue used topically in the treatment of glaucoma. Commonly known side effects include eyelash growth, iris pigmentation and conjunctival hyperemia. While pseudomyopia is reported to be caused by parasympathomimetics, such an effect precipitated by bimatoprost has not yet been reported. We report a case demonstrating pseudomyopia and accommodative spasm caused after starting bimatoprost 0.03% in a young patient with glaucoma. PMID:26598527

A case of gabapentin-induced rhabdomyolysis requiring renal replacement therapy.

PubMed

Choi, Min Seok; Jeon, Howook; Kim, Hyo Suk; Jang, Bo Hyun; Lee, Yoon Hee; Park, Hoon Suk; Kim, HyungWook; Jin, Dong Chan

2017-01-01

Gabapentin is commonly used for controlling convulsions, restless pain syndrome, and pain in diabetic neuropathy. Common side effects include dizziness, somnolence, ataxia, peripheral edema, and confusion; gabapentin-induced rhabdomyolysis is rarely reported. To date, the reported cases of gabapentin-induced rhabdomyolysis have been associated with patients with multiple underlying diseases and assuming multiple medicines for various reasons. In this report, we describe a case of gabapentin-induced rhabdomyolysis in a 32-year-old woman with no medical history. We also review related literature and discuss the possible mechanism and the association with other factors. This case shows that gabapentin can induce rhabdomyolysis in healthy patients and that clinicians must consider the possible association between gabapentin and rhabdomyolysis. © 2016 International Society for Hemodialysis.

Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice.

PubMed

Nishchal, B S; Rai, S; Prabhu, M N; Ullal, Sheetal D; Rajeswari, S; Gopalakrishna, H N

2014-01-01

Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was induced in mice with haloperidol (1.0 mg/kg, intraperitoneally). The first group received the vehicle (10 ml/kg, orally), the second group received trihexyphenidyl (10 mg/kg, orally) and the remaining two groups received Tribulus terrestris (100, 200 mg/kg, orally). The animals were assessed after single and repeated dose administration for ten days, 30 min prior to haloperidol, using standard bar test. The result of the present study demonstrates Tribulus terrestris has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drug used for the same purpose. Our study indicates Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal side effects.

Improvement of side-effects and treatment on the experimental colitis in mice of a resin microcapsule-loading hydrocortisone sodium succinate.

PubMed

Dong, Kai; Zhang, Hefeng; Yan, Yan; Sun, Jinyao; Dong, Yalin; Wang, Ke; Zhang, Lu; Shi, Xianpeng; Xing, Jianfeng

2017-03-01

Extensive or long-time use of corticosteroids often causes many toxic side-effects. The ion exchange resins and the coating material, Eudragit, can be used in combination to form a new oral delivery system to deliver corticosteroids. The resin microcapsule (DRM) composed by Amberlite 717 and Eudragit S100 was used to target hydrocortisone (HC) to the colon in order to improve its treatment effect on ulcerative colitis (UC) and reduce its toxic side-effects. Hydrocortisone sodium succinate (HSS) was sequentially encapsulated in Amberlite 717 and Eudragit S100 to prepare the HSS-loaded resin microcapsule (HSS-DRM). The scanning electron microscopy (SEM) was employed to investigate the morphology and structure of HSS-DRM. The in vitro release and in vivo studies of pharmacokinetics and intestinal drug residues in rat were used to study the colon-targeting of HSS-DRM. The mouse induced by 2,4,6-trinitrobenzenesulfonic acid was used to study the treatment of HSS-DRM on experimental colitis. SEM study showed good morphology and structure of HSS-DRM. In the in vitro release study, > 80% of HSS was released in the colon environment (pH 7.4). The in vivo studies showed good colon-targeting of HSS-DRM (T max  = 0.97 h, C max  = 118.28 µg/mL of HSS; T max  = 2.16 h, C max  = 64.47 µg/mL of HSS-DRM). Moreover, the HSS-DRM could reduce adverse reactions induced by HSS and had good therapeutic effects on the experimental colitis. The resin microcapsule system has good colon-targeting and can be used in the development of colon-targeting preparations.

Differences in Seizure Expression Between Magnetic Seizure Therapy and Electroconvulsive Shock.

PubMed

Cycowicz, Yael M; Rowny, Stefan B; Luber, Bruce; Lisanby, Sarah H

2018-06-01

Evidence suggests that magnetic seizure therapy (MST) results in fewer side effects than electroconvulsive treatment, both in humans treated with electroconvulsive therapy (ECT) as well as in the animal preclinical model that uses electroconvulsive shock (ECS). Evidence suggests that MST results in fewer cognitive side effects than ECT. Although MST offers enhanced control over seizure induction and spread, little is known about how MST and ECT seizures differ. Seizure characteristics are associated with treatment effect. This study presents quantitative analyses of electroencephalogram (EEG) power after electrical and magnetic seizure induction and anesthesia-alone sham in an animal model. The aim was to test whether differential neurophysiological characteristics of the seizures could be identified that support earlier observations that the powers of theta, alpha, and beta but not delta frequency bands were lower after MST when compared with those after ECS. In a randomized, sham-controlled trial, 24 macaca mulatte received 6 weeks of daily sessions while scalp EEG was recorded. Electroencephalogram power was quantified within delta, theta, alpha, and beta frequency bands. Magnetic seizure therapy induced lower ictal expression in the theta, alpha and beta frequencies than ECS, but MST and ECS were indistinguishable in the delta band. Magnetic seizure therapy showed less postictal suppression than ECS. Increasing electrical dosage increased ictal power, whereas increasing MST dosage had no effect on EEG expression. Magnetic seizure therapy seizures have less robust electrophysiological expression than ECS, and these differences are largest in the alpha and beta bands. The relevance of these differences in higher frequency bands to clinical outcomes deserves further exploration. Contrasting EEG in ECS and MST may lead to insights on the physiological underpinnings of seizure-induced amnesia and to finding ways to reduce cognitive side effects.

Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment.

PubMed

Greenlee, Heather; DuPont-Reyes, Melissa J; Balneaves, Lynda G; Carlson, Linda E; Cohen, Misha R; Deng, Gary; Johnson, Jillian A; Mumber, Matthew; Seely, Dugald; Zick, Suzanna M; Boyce, Lindsay M; Tripathy, Debu

2017-05-06

Answer questions and earn CME/CNE Patients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatment-related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mind-body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194-232. © 2017 American Cancer Society. © 2017 American Cancer Society.

Formate-induced inhibition of the water-oxidizing complex of photosystem II studied by EPR.

PubMed

Feyziev, Y M; Yoneda, D; Yoshii, T; Katsuta, N; Kawamori, A; Watanabe, Y

2000-04-04

The effects of various formate concentrations on both the donor and the acceptor sides in oxygen-evolving PS II membranes (BBY particles) were examined. EPR, oxygen evolution and variable chlorophyll fluorescence have been observed. It was found that formate inhibits the formation of the S(2) state multiline signal concomitant with stimulation of the Q(A)(-)Fe(2+) signal at g = 1.82. The decrease and the increase in intensities of the multiline and Q(A)(-)Fe(2+) signals, respectively, had a linear relation for formate concentrations between 5 and 500 mM. The g = 4.1 signal formation measured in the absence of methanol was not inhibited by formate up to 250 mM in the buffer. In the presence of 3% methanol the g = 4.1 signal evolved as formate concentration increased. The evolved signal could be ascribed to the inhibited centers. Oxygen evolution measured in the presence of an electron acceptor, phenyl-p-benzoquinone, was also inhibited by formate proportionally to the decrease in the multiline signal intensity. The inhibition seemed to be due to a retarded electron transfer from the water-oxidizing complex to Y(Z)(+), which was observed in the decay kinetics of the Y(Z)(+) signal induced by illumination above 250 K. These results show that formate induces inhibition of water oxidation reactions as well as electron transfer on the PS II acceptor side. The inhibition effects of formate in PS II were found to be reversible, indicating no destructive effect on the reaction center induced by formate.

Gender specific influence of endogenous glutamate release on stress-induced fear in rats.

PubMed

Jain, S K; Zelena, D

2011-01-01

Stress, fear and anxiety are among major public health concerns. The role of glutamate in these processes is becoming more recognized with promising new drug targets. The aim of this study was to establish the gender specificity of a possible treatment of fear by glutamate antagonists in correspondence with changes in stress-hormone release. Footshock-induced fear was used as an anxiogenic situation in rats. A combination of two ionotrop receptor antagonists such as MK-801 (dizocilpine; 0.2 mg/kg) for NMDA (N-methyl-D-aspartic acid) and GYKI 52466 (benzodiazepine derivative; 10 mg/kg) for AMPA/kainate receptors were used for 5 days following the hypothesis that they potentiate each other the main action, but at the same time the side effects may be minimized. Female rats tried to avoid the electrical stimulus more actively than males, as they spent more time with exploration and jumping and less time with freezing or rest. Ionotropic glutamate receptor antagonists have anxiolytic action. MK-801 was more effective in females, as it prevented the footshock-induced freezing per se, while in males it was effective only in combination with GyKI 52466. The locomotor side effect of MK-801 was not visible after repeated administration. The freezing behavior was positively correlated with the changes in prolactin but not with adrenocorticotropin levels. We proved the involvement of endogenous glutamate neurotransmission in stress-induced fear. Therapeutical usage may involve a combination of different receptor antagonists. Special attention should be paid to the gender, as females seem to be more sensitive, therefore they require smaller doses. During the treatment the prolactin levels should be monitored.

Isolated and combined effects of asymmetric stance and pushing movement on the anticipatory and compensatory postural control.

PubMed

Lee, Yun-Ju; Aruin, Alexander S

2014-04-01

To investigate effects of symmetric and asymmetric stance and pushing movement on anticipatory and compensatory postural adjustments (APAs and CPAs). Ten healthy volunteers stood symmetrically (feet parallel) or asymmetrically (one foot forward and the other backward) and pushed a handle with both hands or right or left hand. Bilateral EMG activity of the trunk and leg muscles and center of pressure (COP) displacements in the anterior-posterior (AP) and medial-lateral (ML) directions were recorded and analyzed during the APAs and CPAs. Isolated asymmetry of stance was associated with larger muscle activity of the backward leg while isolated asymmetry of pushing movement induced larger trunk muscle activity on the contralateral side. A combined asymmetry of stance and pushing movement resulted in the increase or decrease of the thigh muscle activity and ML COP displacement depending on whether both asymmetries were induced on the same side of the body or on opposite sides. Both isolated and combined asymmetries affect APAs and CPAs in pushing. Using combined asymmetry of stance and arm movement might be beneficial in performing pushing activity. The outcome of the study provides a basis for studying postural control in individuals with unilateral impairment while performing daily tasks involving pushing. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Potential involvement of μ-opioid receptor dysregulation on the reduced antinociception of morphine in the inflammatory pain state in mice.

PubMed

Aoki, Yuta; Mizoguchi, Hirokazu; Watanabe, Chizuko; Takeda, Kumiko; Sakurada, Tsukasa; Sakurada, Shinobu

2014-01-01

The antinociceptive effect of morphine in the inflammatory pain state was described in the von Frey filament test using the complete Freund's adjuvant (CFA)-induced mouse inflammatory pain model. After an i.pl. injection of CFA, mechanical allodynia was observed in the ipsilateral paw. The antinociceptive effect of morphine injected s.c. and i.t. against mechanical allodynia was reduced bilaterally at 1 day and 4 days after the CFA pretreatment. The expression level of mRNA for μ-opioid receptors at 1 day after the CFA pretreatment was reduced bilaterally in the lumbar spinal cord and dorsal root ganglion (DRG). In contrast, the protein level of μ-opioid receptors at 1 day after CFA pretreatment was decreased in the ipsilateral side in the DRG but not the lumbar spinal cord. Single or repeated i.t. pretreatment with the protein kinase Cα (PKCα) inhibitor Ro-32-0432 completely restored the reduced morphine antinociception in the contralateral paw but only partially restored it in the ipsilateral paw in the inflammatory pain state. In conclusion, reduced morphine antinociception against mechanical allodynia in the inflammatory pain state is mainly mediated via a decrease in μ-opioid receptors in the ipsilateral side and via the desensitization of μ-opioid receptors in the contralateral side by PKCα-induced phosphorylation.

A system shift in tidal choking due to the construction of Yangshan Harbour, Shanghai, China

NASA Astrophysics Data System (ADS)

Guo, Wenyun; Wang, Xiao Hua; Ding, Pingxing; Ge, Jianzhong; Song, Dehai

2018-06-01

Tidal choking is a geometric feature caused by a narrowed channel. Construction of the Yangshan Harbour, Shanghai, China obstructed three key channels and intensively changed the local geometry and topography. In this study nine numerical experiments based on the Finite-Volume Community Ocean Model are conducted to study the project's influence on tidal characteristics. Results show that stronger tidal choking happened at the East Entrance after project, mainly due to the jet induced water-level drop forced by Bernoulli law and the longer and narrower geometry. The stronger tidal choking forces a faster flow and larger tidal energy flux at the choked channel while reducing the tidal amplitude in the Inner Harbour Area (IHA). The scouring on this channel reduces the choking effect but further enlarges tidal energy flux. Moreover, damming the channels decrease the tidal amplitude at the lee side of tidal propagating direction while increasing the amplitude on the stoss side. The dams also decrease the tidal current on both sides, and meanwhile develop two patches with stronger current aside the dam. The project induced changes in tidal characteristics are complex in space, and perturbations in bathymetry increase this complexity. Yangshan Harbour's construction induces little changes in the total tidal energy density in the IHA, but induces obvious changes in the spatial distribution of tidal energy. Although this study is site-specific, the findings may be applicable to tidal dynamics in land reclamation close to open seas, such as the dramatic reclamation of islands in the South China Sea.

Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments

PubMed Central

McQuade, Rachel M.; Stojanovska, Vanesa; Abalo, Raquel; Bornstein, Joel C.; Nurgali, Kulmira

2016-01-01

Gastrointestinal (GI) side-effects of chemotherapy are a debilitating and often overlooked clinical hurdle in cancer management. Chemotherapy-induced constipation (CIC) and Diarrhea (CID) present a constant challenge in the efficient and tolerable treatment of cancer and are amongst the primary contributors to dose reductions, delays and cessation of treatment. Although prevalence of CIC is hard to estimate, it is believed to affect approximately 16% of cancer patients, whilst incidence of CID has been estimated to be as high as 80%. Despite this, the underlying mechanisms of both CID and CIC remain unclear, but are believed to result from a combination of intersecting mechanisms including inflammation, secretory dysfunctions, GI dysmotility and alterations in GI innervation. Current treatments for CIC and CID aim to reduce the severity of symptoms rather than combating the pathophysiological mechanisms of dysfunction, and often result in worsening of already chronic GI symptoms or trigger the onset of a plethora of other side-effects including respiratory depression, uneven heartbeat, seizures, and neurotoxicity. Emerging treatments including those targeting the enteric nervous system present promising avenues to alleviate CID and CIC. Identification of potential targets for novel therapies to alleviate chemotherapy-induced toxicity is essential to improve clinical outcomes and quality of life amongst cancer sufferers. PMID:27857691

Electron Nuclear Dynamics Simulations of Proton Cancer Therapy Reactions: Water Radiolysis and Proton- and Electron-Induced DNA Damage in Computational Prototypes.

PubMed

Teixeira, Erico S; Uppulury, Karthik; Privett, Austin J; Stopera, Christopher; McLaurin, Patrick M; Morales, Jorge A

2018-05-06

Proton cancer therapy (PCT) utilizes high-energy proton projectiles to obliterate cancerous tumors with low damage to healthy tissues and without the side effects of X-ray therapy. The healing action of the protons results from their damage on cancerous cell DNA. Despite established clinical use, the chemical mechanisms of PCT reactions at the molecular level remain elusive. This situation prevents a rational design of PCT that can maximize its therapeutic power and minimize its side effects. The incomplete characterization of PCT reactions is partially due to the health risks associated with experimental/clinical techniques applied to human subjects. To overcome this situation, we are conducting time-dependent and non-adiabatic computer simulations of PCT reactions with the electron nuclear dynamics (END) method. Herein, we present a review of our previous and new END research on three fundamental types of PCT reactions: water radiolysis reactions, proton-induced DNA damage and electron-induced DNA damage. These studies are performed on the computational prototypes: proton + H₂O clusters, proton + DNA/RNA bases and + cytosine nucleotide, and electron + cytosine nucleotide + H₂O. These simulations provide chemical mechanisms and dynamical properties of the selected PCT reactions in comparison with available experimental and alternative computational results.

Upregulation of CD11b on eosinophils in aspirin induced asthma.

PubMed

Isogai, Sumito; Hayashi, Masamichi; Yamamoto, Naoki; Morishita, Mariko; Minezawa, Tomoyuki; Okamura, Takuya; Hoshino, Tami; Okazawa, Mitsushi; Imaizumi, Kazuyoshi

2013-09-01

Although a challenge test using non-steroidal anti-inflammatory drugs (NSAIDs) is crucial for diagnosis of aspirin-induced asthma (AIA), it also has drawbacks in terms of possible side effects. Therefore, alternative in-vitro diagnostic methods for AIA are awaited. Nineteen stable non-AIA patients (9 males and 10 females; mean age, 49.4 ± 4.8 years), and 20 AIA patients (9 males and 11 females; mean age, 51.1 ± 4.8 years) were enrolled in this study. CD11b and CD16 expressions on the peripheral-blood granulocytes after administration of aspirin and different concentrations of PGE2 in vitro were examined using flowcytometry. Aspirin induced a significant increase in CD11b expression on eosinophils (CD16 negative granulocytes) in 19 AIA patients and one non-AIA patient. Increase in CD11b expression on eosinophils by aspirin administration was suppressed by PGE2 in a dose-dependent manner. The measurement of CD11b expression on peripheral-blood eosinophils showed very high sensitivity and specificity of (-95%) in diagnosing AIA. Although this method requires laboratory facilities for flowcytometry, it may be very useful in diagnosis of AIA without side effects. In addition, PGE2 may be involved in regulation of CD11b expression on eosinophils by aspirin administration.

Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes

PubMed Central

Chang, Jae Won; Park, Keun Hyung; HWANG, Hye Sook; Shin, Yoo Seob; Oh, Young-Taek; Kim, Chul-Ho

2014-01-01

Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways. PMID:24078877

Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes.

PubMed

Chang, Jae Won; Park, Keun Hyung; Hwang, Hye Sook; Shin, Yoo Seob; Oh, Young-Taek; Kim, Chul-Ho

2014-03-01

Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways.

Toxicity of PEG-Coated CoFe2O4 Nanoparticles with Treatment Effect of Curcumin

NASA Astrophysics Data System (ADS)

Akhtar, Shahnaz; An, Wenzhen; Niu, Xiaoying; Li, Kang; Anwar, Shahzad; Maaz, Khan; Maqbool, Muhammad; Gao, Lan

2018-02-01

In this work, CoFe2O4 nanoparticles coated with polyethylene glycol (PEG) were successfully synthesized via a hydrothermal technique. Morphological studies of the samples confirmed the formation of polycrystalline pure-phase PEG-CoFe2O4 nanoparticles with sizes of about 24 nm. Toxicity induced by CoFe2O4 nanoparticles was investigated, and biological assays were performed to check the toxicity effects of CoFe2O4 nanoparticles. Moreover, the healing effect of toxicity induced in living organisms was studied using curcumin and it was found that biochemical indexes detoxified and improved to reach its normal level after curcumin administration. Thus, PEG-coated CoFe2O4 synthesized through a hydrothermal method can be utilized in biomedical applications and curcumin, which is a natural chemical with no side effects, can be used for the treatment of toxicity induced by the nanoparticles in living organisms.

U-Groove aluminum weld strength improvement

NASA Technical Reports Server (NTRS)

Verderaime, V.; Vaughan, R.

1996-01-01

Though butt-welds are among the most preferred joining methods in aerostructures, their strength dependence on inelastic mechanics is generally the least understood. This study investigated experimental strain distributions across a thick aluminum U-grooved weld and identified two weld process considerations for improving the multipass weld strength. The extreme thermal expansion and contraction gradient of the fusion heat input across the groove tab thickness produces severe peaking, which induces bending under uniaxial loading. The filler strain-hardening decreased with increasing filler pass sequence, producing the weakest welds on the last pass side. Current welding schedules unknowingly compound these effects which reduce the weld strength. A depeaking index model was developed to select filler pass thicknesses, pass numbers, and sequences to improve depeaking in the welding process. The intent is to combine the strongest weld pass side with the peaking induced bending tension to provide a more uniform stress and stronger weld under axial tensile loading.

Lamotrigine Induced Whole Body Tics: A Case Report and Literature Review.

PubMed

Centorino, Michael B; Catalano, Glenn; Catalano, Maria C

2016-01-01

Lamotrigine is an anticonvulsant medication that also has utility in the treatment of bipolar disorder. It has been associated with many side effects, including rashes that can progress to Stevens-Johnson syndrome or toxic epidermal necrolysis. It has also been associated with the development of motor tics, most commonly in the head, neck, and shoulders. We will now present the case of a 45-year-old woman who developed tics that involved the entire left side of her body after her dose of lamotrigine was increased from 200 mg daily (2.0 mg/kg/day) to 225 mg daily (2.3 mg/kg/day). We will review the prior cases of lamotrigine induced tics, and compare them to the circumstances surrounding our patient. We will also discuss the neurobiology of tics and make suggestions to improve the tics, based on the reported cases.

Resonance spiking by periodic loss in the double-sided liquid cooling disk oscillator

NASA Astrophysics Data System (ADS)

Nie, Rongzhi; She, Jiangbo; Li, Dongdong; Li, Fuli; Peng, Bo

2017-03-01

A double-sided liquid cooling Nd:YAG disk oscillator working at a pump repetition rate of 20 Hz is demonstrated. The output energy of 376 mJ is realized, corresponding to the optical-optical efficiency of 12.8% and the slope efficiency of 14%. The pump pulse width is 300 µs and the laser pulse width is 260 µs. Instead of being a damped signal, the output of laser comprises undamped spikes. A periodic intra-cavity loss was found by numerical analysis, which has a frequency component near the eigen frequency of the relaxation oscillation. Resonance effect will induce amplified spikes even though the loss fluctuates in a small range. The Shark-Hartmann sensor was used to investigate the wavefront aberration induced by turbulent flow and temperature gradient. According to the wavefront and fluid mechanics analysis, it is considered that the periodic intra-cavity loss can be attributed to turbulent flow and temperature gradient.

Hydroxyurea-induced oral ulceration.

PubMed

Badawi, Maha; Almazrooa, Soulafa; Azher, Fatima; Alsayes, Fatin

2015-12-01

Hydroxyurea is an antimetabolite that is widely used in the treatment of many benign and malignant conditions. This drug is usually well tolerated but has a number of side effects that vary in incidence. In cases of clinically significant adverse events, hydroxyurea is usually discontinued either temporarily or permanently, depending on treatment need versus harm caused by side effects. Here, we report a case of oral ulceration associated with hydroxyurea treatment in a patient who had chronic myelogenous leukemia. The patient rapidly developed an oral ulcer 12 days after administration of the drug. Hydroxyurea was discontinued, and the oral lesion appreciably decreased in size and severity. Physicians and dentists should be aware of the association between hydroxyurea and oral lesions. Copyright © 2015 Elsevier Inc. All rights reserved.

Predictors of long-term compliance in attending a worksite hypertension programme.

PubMed

Landers, R; Riccobene, A; Beyreuther, M; Neusy, A J

1993-12-01

Variables such as patient's anxiety, knowledge, number of medication changes, medication-induced side-effects and programme-derived benefits and conveniences have been reported or theorised to be important determinants of patient's attendance at worksite hypertension programmes. This study investigates whether these variables have predictive value in differentiating compliers from noncompliers attending a union-sponsored worksite hypertension programme for at least five years. Scores were created from a questionnaire distributed to 243 patients with a response rate of 98%. Compliance was defined as missing < or = 25% of scheduled clinic appointments. By discriminant statistical analysis scores for patient's anxiety, knowledge, number of medication changes, medication side-effects, perceived benefits and conveniences failed to show any predictive value for patient's compliance with appointment keeping.

Ascorbic acid transported by sodium-dependent vitamin C transporter 2 stimulates steroidogenesis in human choriocarcinoma cells.

PubMed

Wu, Ximei; Iguchi, Takuma; Itoh, Norio; Okamoto, Kousuke; Takagi, Tatsuya; Tanaka, Keiichi; Nakanishi, Tsuyoshi

2008-01-01

Reduced vitamin C [ascorbic acid (AA)], which is taken up into cells by sodium-dependent vitamin C transporter (SVCT) 1 and 2, is believed to be important for hormone synthesis, but its role in generating placental steroids needed to maintain pregnancy and fetal development is not clear. To determine the steroidogenic effect of AA and the role of SVCT2 in AA-induced steroidogenesis, we tested the effects of AA treatment and SVCT2 knockdown on steroidogenesis in human choriocarcinoma cell lines. AA treatment of JEG-3, BeWo, and JAR cells for 48-h dose dependently increased progesterone and estradiol levels. In JEG-3 cells, AA increased the mRNA expression of P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase, key enzymes for steroidogenesis. Stable knockdown of SVCT2 in JEG-3 cells by retrovirally mediated RNA interference decreased the maximal velocity of AA uptake by approximately 50%, but apparent affinity values were not affected. SVCT2 knockdown in JEG-3 cells significantly suppressed the AA-induced mRNA expression of placental P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase. This suppression of the AA-induced mRNA expression of steroidogenic enzymes subsequently decreased progesterone and estradiol production. In addition, inhibition of MAPK kinase-ERK signaling, which is a major pathway for AA-regulated gene expression, failed to affect AA-induced steroidogenesis. Our observations indicate that SVCT2-mediated AA uptake into cells is necessary for AA-induced steroidogenesis in human choriocarcinoma cell, but MAPK kinase-ERK signaling is not involved in AA-induced steroidogenesis.

Large Eddy Simulation of turbulence induced secondary flows in stationary and rotating straight square ducts

NASA Astrophysics Data System (ADS)

Sudjai, W.; Juntasaro, V.; Juttijudata, V.

2018-01-01

The accuracy of predicting turbulence induced secondary flows is crucially important in many industrial applications such as turbine blade internal cooling passages in a gas turbine and fuel rod bundles in a nuclear reactor. A straight square duct is popularly used to reveal the characteristic of turbulence induced secondary flows which consists of two counter rotating vortices distributed in each corner of the duct. For a rotating duct, the flow can be divided into the pressure side and the suction side. The turbulence induced secondary flows are converted to the Coriolis force driven two large circulations with a pair of additional vortices on the pressure wall due to the rotational effect. In this paper, the Large Eddy Simulation (LES) of turbulence induced secondary flows in a straight square duct is performed using the ANSYS FLUENT CFD software. A dynamic kinetic energy subgrid-scale model is used to describe the three-dimensional incompressible turbulent flows in the stationary and the rotating straight square ducts. The Reynolds number based on the friction velocity and the hydraulic diameter is 300 with the various rotation numbers for the rotating cases. The flow is assumed fully developed by imposing the constant pressure gradient in the streamwise direction. For the rotating cases, the rotational axis is placed perpendicular to the streamwise direction. The simulation results on the secondary flows and the turbulent statistics are found to be in good agreement with the available Direct Numerical Simulation (DNS) data. Finally, the details of the Coriolis effects are discussed.

Effectiveness and Safety of Newer Antidiabetic Medications for Ramadan Fasting Diabetic Patients

PubMed Central

2016-01-01

Hypoglycemia is the most common side effects for most glucose-lowering therapies. It constitutes a serious risk that faces diabetic patients who fast during Ramadan (the 9th month in the Islamic calendar). New glucose-lowering classes like dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are efficacious in controlling blood glucose level with less tendency to induce hypoglycemia and thus may constitute a good choice for diabetic patients during Ramadan. This study reviews the safety and efficacy of newer glucose-lowering therapies during Ramadan. This study was accomplished through a careful literature search about studies that assess the benefit and side effects of these new glucose-lowering therapies during Ramadan during September 2015. Vildagliptin, sitagliptin, liraglutide, exenatide, and dapagliflozin were the only studied glucose-lowering therapies. All of the studied newer glucose-lowering therapies except dapagliflozin were associated with reduced risk to induce hypoglycemia. Gastrointestinal upset was common with the usage of liraglutide while increased thirst sensation was common with dapagliflozin. In conclusion DPP-4 inhibitors such as vildagliptin and sitagliptin may form a suitable glucose-lowering therapy option for Ramadan fasting patients. PMID:27642611

Salting effects on protein components in aqueous NaCl and urea solutions: toward understanding of urea-induced protein denaturation.

PubMed

Li, Weifeng; Zhou, Ruhong; Mu, Yuguang

2012-02-02

The mechanism of urea-induced protein denaturation is explored through studying the salting effect of urea on 14 amino acid side chain analogues, and N-methylacetamide (NMA) which mimics the protein backbone. The solvation free energies of the 15 molecules were calculated in pure water, aqueous urea, and NaCl solutions. Our results show that NaCl displays strong capability to salt out all 15 molecules, while urea facilitates the solvation (salting-in) of all the 15 molecules on the other hand. The salting effect is found to be largely enthalpy-driven for both NaCl and urea. Our observations can explain the higher stability of protein's secondary and tertiary structures in typical salt solutions than that in pure water. Meanwhile, urea's capability to better solvate protein backbone and side-chain components can be extrapolated to explain protein's denaturation in aqueous urea solution. Urea salts in molecules through direct binding to solute surface, and the strength is linearly dependent on the number of heavy atoms of solute molecules. The van der Waals interactions are found to be the dominant force, which challenges a hydrogen-bonding-driven mechanism proposed previously.

Sulphur alters NFκB-p300 cross-talk in favour of p53-p300 to induce apoptosis in non-small cell lung carcinoma.

PubMed

Saha, Shilpi; Bhattacharjee, Pushpak; Guha, Deblina; Kajal, Kirti; Khan, Poulami; Chakraborty, Sreeparna; Mukherjee, Shravanti; Paul, Shrutarshi; Manchanda, Rajkumar; Khurana, Anil; Nayak, Debadatta; Chakrabarty, Rathin; Sa, Gaurisankar; Das, Tanya

2015-08-01

Adverse side effects of chemotherapy during cancer treatment have shifted considerable focus towards therapies that are not only targeted but are also devoid of toxic side effects. We evaluated the antitumorigenic activity of sulphur, and delineated the molecular mechanisms underlying sulphur-induced apoptosis in non-small cell lung carcinoma (NSCLC) cells. A search for the underlying mechanism revealed that the choice between the two cellular processes, NFκBp65-mediated survival and p53-mediated apoptosis, was decided by the competition for a limited pool of transcriptional coactivator protein p300 in NSCLC cells. In contrast, sulphur inhibited otherwise upregulated survival signaling in NSCLC cells by perturbing the nuclear translocation of p65NFκB, its association with p300 histone acetylase, and subsequent transcription of Bcl-2. Under such anti-survival condition, induction of p53-p300 cross-talk enhanced the transcriptional activity of p53 and intrinsic mitochondrial death cascade. Overall, the findings of this preclinical study clearly delineated the molecular mechanism underlying the apoptogenic effect of the non-toxic homeopathic remedy, sulphur, in NSCLC cells.

Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis.

PubMed

Broersen, Leonie H A; Jha, Meghna; Biermasz, Nienke R; Pereira, Alberto M; Dekkers, Olaf M

2018-05-31

To systematically review the effectiveness of medical treatment for Cushing's syndrome in clinical practice, regarding cortisol secretion, clinical symptom improvement, and quality of life. To assess the occurrence of side effects of these medical therapies. Eight electronic databases were searched in March 2017 to identify potentially relevant articles. Randomized controlled trials and cohort studies assessing the effectiveness of medical treatment in patients with Cushing's syndrome, were eligible. Pooled proportions were reported including 95% confidence intervals. We included 35 articles with in total 1520 patients in this meta-analysis. Most included patients had Cushing's disease. Pooled reported percentage of patients with normalization of cortisol ranged from 35.7% for cabergoline to 81.8% for mitotane in Cushing's disease. Patients using medication monotherapy showed a lower percentage of cortisol normalization compared to use of multiple medical agents (49.4 vs. 65.7%); this was even higher for patients with concurrent or previous radiotherapy (83.6%). Mild side effects were reported in 39.9%, and severe side effects were seen in 15.2% of patients after medical treatment. No meta-analyses were performed for clinical symptom improvement or quality of life due to lack of sufficient data. This meta-analysis shows that medication induces cortisol normalization effectively in a large percentage of patients. Medical treatment for Cushing's disease patients is thus a reasonable option in case of a contraindication for surgery, a recurrence, or in patients choosing not to have surgery. When experiencing side effects or no treatment effect, an alternate medical therapy or combination therapy can be considered.

HIV post exposure prophylaxis induced bicytopenia: a case report

PubMed Central

2014-01-01

Long and short term side effects of antiretroviral drugs are not fully understood yet. Here a case of reversible blood count changes following post exposure prophylaxis with tenofovir/emtricitabin and lopinavir/ritonavir is reported. We propose that antiretroviral drugs used in post exposure prophylaxis may have a significant impact on hematopoiesis. PMID:24506969

IREPS (Integrated Refractive Effects Prediction System) 3.0. (User’s Manual).

DTIC Science & Technology

1987-09-01

heating from exhaust vents or solar-heated surfaces. These measurements are best performed with a psychrometer on the most windward side of the ship...Celsius and is best measured with a hand-held psychrometer at any location above 6 meters (20 feet). Care should be taken to minimize any ship-induced

Large Enhancement of the Sagnac Effect Based on Nonlinearly Induced Nonreciprocity.

DTIC Science & Technology

1983-05-30

Og4 ,, % 20. ABSTRACT (Continue on reverse side It ne c,&aty and Identify by block number) LL On Back -°. La . -k. DD 1JAN73 1473 EDITION OF ’NOV6S...be published. 8. L. A. Hackel, R. P. Hackel, and S. Ezekiel, Metrologia 13, 141 (1977). Ř. .4

Novel angiogenesis inhibitory activity in cinnamon extract blocks VEGFR2 kinase and downstream signaling

USDA-ARS?s Scientific Manuscript database

VEGF is one of the most critical factors that induce angiogenesis, and has thus become an attractive target for anti-angiogenesis treatment. However, most of the current anti-VEGF agents that often cause side effects cannot be recommended for long term use. Identification of natural VEGF inhibitors...

Innate Immune Response and Off-Target Mis-splicing Are Common Morpholino-Induced Side Effects in Xenopus.

PubMed

Gentsch, George E; Spruce, Thomas; Monteiro, Rita S; Owens, Nick D L; Martin, Stephen R; Smith, James C

2018-03-12

Antisense morpholino oligomers (MOs) have been indispensable tools for developmental biologists to transiently knock down (KD) genes rather than to knock them out (KO). Here we report on the implications of genetic KO versus MO-mediated KD of the mesoderm-specifying Brachyury paralogs in the frog Xenopus tropicalis. While both KO and KD embryos fail to activate the same core gene regulatory network, resulting in virtually identical morphological defects, embryos injected with control or target MOs also show a systemic GC content-dependent immune response and many off-target splicing defects. Optimization of MO dosage and increasing incubation temperatures can mitigate, but not eliminate, these MO side effects, which are consistent with the high affinity measured between MO and off-target sequence in vitro. We conclude that while MOs can be useful to profile loss-of-function phenotypes at a molecular level, careful attention must be paid to their immunogenic and off-target side effects. Copyright © 2018 The Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

Single dose regorafenib-induced hypertensive crisis.

PubMed

Yilmaz, B; Kemal, Y; Teker, F; Kut, E; Demirag, G; Yucel, I

2014-06-01

Gastrointestinal stromal tumors (GISTs) are uncommon tumors of the gastrointestinal (GI) tract. Regorafenib is a new multikinase inhibitor and is approved for the treatment of GISTs in patients who develop resistance to imatinib and sunitinib. The most common drug-related adverse events with regorafenib are hypertension, hand-foot skin reactions, and diarrhea. Grade IV hypertensive side effect has never been reported after a single dose. In this report, we present a case of Grade IV hypertensive side effect (hypertensive crisis and seizure) after a single dose of regorafenib. A 54-year-old male normotensive GIST patient was admitted to the emergency department with seizure and encephalopathy after the first dosage of regorafenib. His blood pressure was 240/140 mmHg upon admission. After intensive treatment with nitrate and nitroprusside, his blood pressure returned to normal levels in five days. Regorafenib was discontinued, and he did not experience hypertension again. This paper reports the first case of Grade IV hypertension after the first dosage of regorafenib. We can suggest that hypertension is an idiosyncratic side effect unrelated to the dosage.

Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction

NASA Astrophysics Data System (ADS)

Park, Jae Hong; Hong, Jin Ki; Jang, Ja Yun; An, Jieun; Lee, Kyu-Sung; Kang, Tong Mook; Shin, Hyun Joon; Suh, Jun-Kyo Francis

2017-01-01

As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method. The results showed that depolarizing ChR2-SMCs with blue light induced bladder contraction, whereas hyperpolarizing NpHR-SMCs with yellow light suppressed PGE2-induced overactive contraction. We also confirmed that optogenetic contraction of bladder smooth muscles in this study is not neurogenic, but solely myogenic, and that optogenetic light stimulation can modulate the urination in vivo. This study thus demonstrated the utility of optogenetic modulation of smooth muscle as a means to actively control the urinary bladder contraction with spatial and temporal accuracy. These features would increase the efficacy of bladder control in LUT dysfunctions without the side effects of conventional clinical therapies.

New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma.

PubMed

Behling, Juliane; Kaes, Joachim; Münzel, Thomas; Grabbe, Stephan; Loquai, Carmen

2017-04-01

There has been considerable progress in treating malignant melanoma over the last few years. The immune-checkpoint-inhibitors nivolumab and pembrolizumab have been approved by the Food and Drug Administration in 2014 for the therapy of metastatic melanoma. Anti-programmed cell death-1-blocking antibodies are known to cause immune-related adverse events. Physicians should be aware of common and rare side effects and pay attention to new ones. We therefore report a severe and life-threatening side effect of anti-programmed cell death-1 immunotherapy with nivolumab that has not been previously reported: the development of a third-degree atrioventricular block. After a second infusion with nivolumab, our patient developed a troponin I-positive and autoantibody-positive myositis and a few days later a new-onset third-degree atrioventricular block. This is most likely because of an autoimmune-induced myositis with a cardiac impairment in terms of a myocarditis, which led to an impairment of the conduction of cardiac electrical stimuli.

Low-level laser therapy (LLLT) does not reduce subcutaneous adipose tissue by local adipocyte injury but rather by modulation of systemic lipid metabolism.

PubMed

Jankowski, Marek; Gawrych, Mariusz; Adamska, Urszula; Ciescinski, Jakub; Serafin, Zbigniew; Czajkowski, Rafal

2017-02-01

Low-level laser (light) therapy (LLLT) has been applied recently to body contouring. However the mechanism of LLLT-induced reduction of subcutaneous adipose tissue thickness has not been elucidated and proposed hypotheses are highly controversial. Non-obese volunteers were subject to 650nm LLLT therapy. Each patient received 6 treatments 2-3 days apart to one side of the abdomen. The contralateral side was left untreated and served as control. Subjects' abdominal adipose tissue thickness was measured by ultrasound imaging at baseline and 2 weeks post-treatment. Our study is to the best of our knowledge, the largest split-abdomen study employing subcutaneous abdominal fat imaging. We could not show a statistically significant reduction of abdominal subcutaneous adipose tissue by LLLT therapy. Paradoxically when the measurements of the loss of fat thickness on treated side was corrected for change in thickness on non treated side, we have observed that in 8 out of 17 patients LLLT increased adipose tissue thickness. In two patients severe side effect occurred as a result of treatment: one patient developed ulceration within appendectomy scar, the other over the posterior superior iliac spine. The paradoxical net increase in subcutaneous fat thickness observed in some of our patients is a rationale against liquefactive and transitory pore models of LLLT-induced adipose tissue reduction. LLLT devices with laser diode panels applied directly on the skin are not as safe as devices with treatment panels separated from the patient's skin.

Dental changes evaluated with a 3D computer-assisted model analysis after long-term tongue retaining device wear in OSA patients.

PubMed

Chen, Hui; Lowe, Alan A; Strauss, Arthur M; de Almeida, Fernanda Riberiro; Ueda, Hiroshi; Fleetham, John A; Wang, Bangkang

2008-05-01

Oral appliances (OAs) have been used to treat obstructive sleep apnea (OSA) patients for decades. However, detailed dental side effects in long-term OA cases analyzed with an accurate three-dimensional (3D) measurement tool have seldom been reported. The purpose of this study is to evaluate dental side effects in five OSA patients, who had used a tongue retaining device (TRD) (with occasional other OA wear) for an average of 6 years and 4 months. The baseline and follow-up orthodontic study models were measured with a newly developed MicroScribe-3DX analysis system. High compliance of TRD wear was confirmed in all cases and different patterns and amounts of dental changes were observed. The most common appliance-induced dental changes included anterior and/or unilateral posterior open-bites and reduced anterior overjets. It was hypothesized that there might be two possible mechanisms for the TRD side effects--one is the forward pressure of the tongue upon the anterior dental arch and the other is the lateral pressure of the tongue upon the posterior arch. Considerations to correct the TRD dental side effects should be guided by these different mechanisms of the tongue on the dental arch. Possible solutions to minimize occlusal changes and maximize the benefits for OSA patients are also discussed.

Carbon dioxide laser versus erbium:YAG laser in treatment of epidermal verrucous nevus: a comparative randomized clinical study.

PubMed

Osman, Mai Abdel Raouf; Kassab, Ahmed Nazmi

2017-08-01

A verrucous epidermal nevus (VEN) is a skin disorder that has been treated using different treatment modalities with varying results. Ablative lasers such as carbon dioxide laser (CO 2 ) and erbium:yttrium-aluminum-garnet (Er:YAG) laser have been considered as the gold standard for the treatment of epidermal nevi. To evaluate and compare the efficacy, postoperative wound healing and side effects of pulsed CO 2 laser and Er:YAG laser for the treatment of verrucous epidermal nevi. Twenty patients with localized VEN were randomly divided into two groups. Group 1 was administered CO 2 laser and group 2 underwent Er:YAG laser treatment. A blinded physician evaluated the photographs and dermoscopic photomicrographs for the efficacy and possible side effects. All patients received one treatment session and were followed up over a 6-month period. Both lasers induced noticeable clinical improvement, but there were no significant differences between two lasers in treatment response, patient satisfaction, duration of erythema and side effects. The average time to re-epithelialization was 13.5 days with CO 2 and 7.9 days with Er:YAG laser (p< .0005). No scarring was observed in Er:YAG laser group and no lesional recurrence was detected in CO 2 laser group since treatment. Apart from re-epithelialization, both lasers showed equivalent outcomes with respect to treatment response, patient satisfaction, side effects and complications.

Effect of flomoxef on blood coagulation and alcohol metabolism.

PubMed

Uchida, K; Matsubara, T

1991-01-01

The effect of flomoxef, a newly developed oxacephem antibiotic with an N-hydroxyethyltetrazolethiol (HTT) side chain, on blood coagulation and alcohol metabolism was compared with that of a series of cephalosporin antibiotics with N-methyltetrazolethiol (NMTT), thiadiazolethiol (TDT) or methylthiadiazolethiol (MTDT) side chains in position 3' of the cephalosporin nucleus known to cause hypoprothrombinemia and bleeding in patients who are malnourished, debilitated and/or of high age. A disulfiram-like effect caused by inhibition of aldehyde dehydrogenase was observed for NMTT-containing antibiotics. Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g flomoxef i.v. once or twice daily in five and six healthy male volunteers, respectively, did not cause any significant changes in prothrombin time (PT), coagulation factors II, VII, IX or X, in hepaplastin values or fibrinogen levels, activated partial thromboplastin time (APTT), platelet counts, bleeding time, or collagen- and ADP-induced platelet aggregation. Inhibition of vitamin K epoxide reductase was observed in rats treated with flomoxef, yet to a much lesser extent than observed for cephalosporins with NMTT, TDT or MTDT side chains. This defect was quickly normalized by vitamin K injection. There were no differences between oxacephem (1-O) and cephem (1-S) compounds with respect to effects on blood clotting and platelet aggregation. Flomoxef and its side chain HTT showed no influence on alcohol metbolism.

Effective prevention of sorafenib-induced hand-foot syndrome by dried-bonito broth.

PubMed

Kamimura, Kenya; Shinagawa-Kobayashi, Yoko; Goto, Ryo; Ogawa, Kohei; Yokoo, Takeshi; Sakamaki, Akira; Abe, Satoshi; Kamimura, Hiroteru; Suda, Takeshi; Baba, Hiroshi; Tanaka, Takayuki; Nozawa, Yoshizu; Koyama, Naoto; Takamura, Masaaki; Kawai, Hirokazu; Yamagiwa, Satoshi; Aoyagi, Yutaka; Terai, Shuji

2018-01-01

Sorafenib (SOR) is a molecular medicine that prolongs the survival of patients with hepatocellular carcinoma (HCC). Therefore, the management of side effects is essential for the longer period of continuous medication. Among the various side effects, hand-foot syndrome (HFS) is the most common, occurring in 30%-50% of patients, and often results in discontinuation of the SOR medication. However, its mechanism has not been clarified, and no effective prevention method has been reported for the symptoms. Therefore, this study aimed to analyze its mechanism and to develop an effective prevention regimen for the symptoms. To assess the mechanism of SOR-induced HFS, the peripheral blood flow in the hand and foot was carefully monitored by Doppler ultrasound, thermography, and laser speckle flowgraphy in the cases treated with SOR and its contribution was assessed. Then, the effect of dried-bonito broth (DBB), which was reported to improve peripheral blood flow, on the prevention of the symptom was examined by monitoring its occurrence and the peripheral blood flow. A total of 25 patients were enrolled in this study. In all, eight patients developed HFS, and all cases showed a significant decrease in the peripheral blood flow. DBB contributed to an increase in the flow ( p = 0.009) and significantly decreased occurrence of HFS ( p = 0.005) than control. Multivariable analysis showed that the ingestion of DBB is a significant independent contributor to HFS-free survival period ( p = 0.035). The mechanism of SOR-induced HFS involves a decrease in the peripheral blood flow, and the ingestion of DBB effectively prevents the development of the syndrome by maintaining the flow.

Heterogeneity of colon cancer: from bench to bedside

PubMed Central

Merlano, Marco C; Granetto, Cristina; Fea, Elena; Ricci, Vincenzo; Garrone, Ornella

2017-01-01

The large bowel shows biomolecular, anatomical and bacterial changes that proceed from the proximal to the distal tract. These changes account for the different behaviour of colon cancers arising from the diverse sides of the colon–rectum as well as for the sensitivity to the therapy, including immunotherapy. The gut microbiota plays an important role in the modulation of the immune response and differs between the right colon cancer and the left colorectal cancer. The qualitative and quantitative difference of the commensal bacteria between the right side and the left side induces epigenetic changes in the intestinal epithelial cells as well as in the resident immune population. The second player in the pathological homeostasis of colorectal cancer is the differences of the genetic features of cancer cells and the different effects that microsatellite instability, chromosomal instability and the CpG island methylator phenotype induce on the immunological organisation of the tumour microenvironment. The third player is the immunological composition of the tumour microenvironment, which changes under the influence of both genetic structures and gut microbiota. All these three players influence each other. This review describes these three aspects, highlights their interactions and discusses data from reported clinical trials. Click here to listen to the Podcast PMID:29209524

U-Groove Aluminum Weld Strength Improvement

NASA Technical Reports Server (NTRS)

Verderaime, V.; Vaughan, R.

1997-01-01

Though butt-welds are among the most preferred joining methods in aerostructures, their strength dependence on inelastic mechanics is generally the least understood. This study investigated experimental strain distributions across a thick aluminum U-grooved weld and identified two weld process considerations for improving the multipass weld strength. One is the source of peaking in which the extreme thermal expansion and contraction gradient of the fusion heat input across the groove tab thickness produces severe angular distortion that induces bending under uniaxial loading. The other is the filler strain hardening decreasing with increasing filler pass sequences, producing the weakest welds on the last weld pass side. Both phenomena are governed by weld pass sequences. Many industrial welding schedules unknowingly compound these effects, which reduce the weld strength. A depeaking index model was developed to select filler pass thickness, pass numbers, and sequences to improve depeaking in the welding process. The result was to select the number and sequence of weld passes to reverse the peaking angle such as to combine the strongest weld pass side with the peaking induced bending tension component side to provide a more uniform stress and stronger weld under axial tensile loading.

Lee-side flow over delta wings at supersonic speeds

NASA Technical Reports Server (NTRS)

Miller, D. S.; Wood, R. M.

1985-01-01

An experimental investigation of the lee-side flow on sharp leading-edge delta wings at supersonic speeds has been conducted. Pressure data were obtained at Mach numbers from 1.5 to 2.8, and three types of flow-visualization data (oil-flow, tuft, and vapor-screen) were obtained at Mach numbers from 1.7 to 2.8 for wing leading-edge sweep angles from 52.5 deg to 75 deg. From the flow-visualization data, the lee-side flows were classified into seven distinct types and a chart was developed that defines the flow mechanism as a function of the conditions normal to the wing leading edge, specifically, angle of attack and Mach number. Pressure data obtained experimentally and by a semiempirical prediction method were employed to investigate the effects of angle of attack, leading-edge sweep, and Mach number on vortex strength and vortex position. In general, the predicted and measured values of vortex-induced normal force and vortex position obtained from experimental data have the same trends with angle of attack, Mach number, and leading-edge sweep; however, the vortex-induced normal force is underpredicted by 15 to 30 percent, and the vortex spanwise location is overpredicted by approximately 15 percent.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canavan, G.H.

Optimizations of missile allocation based on linearized exchange equations produce accurate allocations, but the limits of validity of the linearization are not known. These limits are explored in the context of the upload of weapons by one side to initially small, equal forces of vulnerable and survivable weapons. The analysis compares analytic and numerical optimizations and stability induces based on aggregated interactions of the two missile forces, the first and second strikes they could deliver, and they resulting costs. This note discusses the costs and stability indices induced by unilateral uploading of weapons to an initially symmetrical low force configuration.more » These limits are quantified for forces with a few hundred missiles by comparing analytic and numerical optimizations of first strike costs. For forces of 100 vulnerable and 100 survivable missiles on each side, the analytic optimization agrees closely with the numerical solution. For 200 vulnerable and 200 survivable missiles on each side, the analytic optimization agrees with the induces to within about 10%, but disagrees with the allocation of the side with more weapons by about 50%. The disagreement comes from the interaction of the possession of more weapons with the shift of allocation from missiles to value that they induce.« less

Compound 331 selectively induces glioma cell death by upregulating miR-494 and downregulating CDC20

PubMed Central

Zhang, Lei; Niu, Tianhui; Huang, Yafei; Zhu, Haichuan; Zhong, Wu; Lin, Jian; Zhang, Yan

2015-01-01

Malignant gliomas are the most common malignant tumors in the central nervous system (CNS). Up to date, the prognosis of glioma is still very poor, effective therapy with less side-effect is very necessary. Herein, we identify a compound named as “331” selectively induced cell death in glioma cells but not in astrocytes. Compound 331 upregulated miR-494 and downregulated CDC20 in glioma cells but not in astrocytes. These results suggest that compound 331 could be a potential drug selectively targeting glioma cells through upregulating miR-494 and downregulating CDC20. PMID:26153143

Novel Antipsychotics in the Treatment of Behavioral Disturbances and Psychoses Associated With Neurodegenerative Disorders

PubMed Central

Masand, Prakash S.

2000-01-01

Behavioral disturbances and psychosis are common features of neurodegenerative disorders and may be drug induced, intrinsic to the underlying pathology, or both. These disturbances, including psychotic and mood symptoms, apathy, aggression and other behavioral symptoms, and superimposed delirium, cause a great amount of disability to the patient and stress on the caregiver. Conventional neuroleptics have been shown to be effective in the treatment of these symptoms, but unacceptable side effects may occur. However, the novel antipsychotics, with their lower risk of inducing extrapyramidal symptoms, have shown promise in the treatment of behavioral disturbances and psychosis associated with neurodegenerative disorders. PMID:15014653

Rehabilitation Exercises to Induce Balanced Scapular Muscle Activity in an Anti-gravity Posture

PubMed Central

Ishigaki, Tomonobu; Yamanaka, Masanori; Hirokawa, Motoki; Tai, Keita; Ezawa, Yuya; Samukawa, Mina; Tohyama, Harukazu; Sugawara, Makoto

2014-01-01

[Purpose] The purpose of this study was to compare the intramuscular balance ratios of the upper trapezius muscle (UT) and the lower trapezius muscle (LT), and the intermuscular balance ratios of the UT and the serratus anterior muscle (SA) among prone extension (ProExt), prone horizontal abduction with external rotation (ProHAbd), forward flexion in the side-lying position (SideFlex), side-lying external rotation (SideEr), shoulder flexion with glenohumeral horizontal abduction load (FlexBand), and shoulder flexion with glenohumeral horizontal adduction load (FlexBall) in the standing posture. [Methods] The electromyographic (EMG) activities of the UT, LT and SA were measured during the tasks. The percentage of maximum voluntary isometric contraction (%MVIC) was calculated for each muscle, and the UT/LT ratios and the UT/SA ratios were compared among the tasks. [Results] The UT/LT ratio with the FlexBand was not significantly different from those of the four exercises in the side-lying and prone postures. The UT/SA ratio with the FlexBall demonstrated appropriate balanced activity. [Conclusion] In an anti-gravity posture, we recommend the FlexBand and the FlexBall for inducing balanced UT/LT and UT/SA ratios, respectively. PMID:25540485

Rehabilitation Exercises to Induce Balanced Scapular Muscle Activity in an Anti-gravity Posture.

PubMed

Ishigaki, Tomonobu; Yamanaka, Masanori; Hirokawa, Motoki; Tai, Keita; Ezawa, Yuya; Samukawa, Mina; Tohyama, Harukazu; Sugawara, Makoto

2014-12-01

[Purpose] The purpose of this study was to compare the intramuscular balance ratios of the upper trapezius muscle (UT) and the lower trapezius muscle (LT), and the intermuscular balance ratios of the UT and the serratus anterior muscle (SA) among prone extension (ProExt), prone horizontal abduction with external rotation (ProHAbd), forward flexion in the side-lying position (SideFlex), side-lying external rotation (SideEr), shoulder flexion with glenohumeral horizontal abduction load (FlexBand), and shoulder flexion with glenohumeral horizontal adduction load (FlexBall) in the standing posture. [Methods] The electromyographic (EMG) activities of the UT, LT and SA were measured during the tasks. The percentage of maximum voluntary isometric contraction (%MVIC) was calculated for each muscle, and the UT/LT ratios and the UT/SA ratios were compared among the tasks. [Results] The UT/LT ratio with the FlexBand was not significantly different from those of the four exercises in the side-lying and prone postures. The UT/SA ratio with the FlexBall demonstrated appropriate balanced activity. [Conclusion] In an anti-gravity posture, we recommend the FlexBand and the FlexBall for inducing balanced UT/LT and UT/SA ratios, respectively.

Protective effect of Korean Red Ginseng against chemotherapeutic drug-induced premature catagen development assessed with human hair follicle organ culture model

PubMed Central

Keum, Dong In; Pi, Long-Quan; Hwang, Sungjoo Tommy; Lee, Won-Soo

2015-01-01

Background Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects for patients undergoing chemotherapy. This study evaluated the protective effect of Korean Red Ginseng (KRG) on CIA in a well-established in vitro human hair follicle organ culture model as it occurs in vivo. Methods We examined whether KRG can prevent premature hair follicle dystrophy in a human hair follicle organ culture model during treatment with a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC). Results 4-HC inhibited human hair growth, induced premature catagen development, and inhibited proliferation and stimulated apoptosis of hair matrix keratinocytes. In addition, 4-HC increased p53 and Bax protein expression and decreased Bcl2 protein expression. Pretreatment with KRG protected against 4-HC-induced hair growth inhibition and premature catagen development. KRG also suppressed 4-HC-induced inhibition of matrix keratinocyte proliferation and stimulation of matrix keratinocyte apoptosis. Moreover, KRG restored 4-HC-induced p53 and Bax/Bcl2 expression. Conclusion Overall, our results indicate that KRG may protect against 4-HC-induced premature catagen development through modulation of p53 and Bax/Bcl2 expression. PMID:27158238

Protective effect of Korean Red Ginseng against chemotherapeutic drug-induced premature catagen development assessed with human hair follicle organ culture model.

PubMed

Keum, Dong In; Pi, Long-Quan; Hwang, Sungjoo Tommy; Lee, Won-Soo

2016-04-01

Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects for patients undergoing chemotherapy. This study evaluated the protective effect of Korean Red Ginseng (KRG) on CIA in a well-established in vitro human hair follicle organ culture model as it occurs in vivo. We examined whether KRG can prevent premature hair follicle dystrophy in a human hair follicle organ culture model during treatment with a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC). 4-HC inhibited human hair growth, induced premature catagen development, and inhibited proliferation and stimulated apoptosis of hair matrix keratinocytes. In addition, 4-HC increased p53 and Bax protein expression and decreased Bcl2 protein expression. Pretreatment with KRG protected against 4-HC-induced hair growth inhibition and premature catagen development. KRG also suppressed 4-HC-induced inhibition of matrix keratinocyte proliferation and stimulation of matrix keratinocyte apoptosis. Moreover, KRG restored 4-HC-induced p53 and Bax/Bcl2 expression. Overall, our results indicate that KRG may protect against 4-HC-induced premature catagen development through modulation of p53 and Bax/Bcl2 expression.

In vitro and in vivo Effects of Free and Chalcones-Loaded Nanoemulsions: Insights and Challenges in Targeted Cancer Chemotherapies

PubMed Central

Winter, Evelyn; Dal Pizzol, Carine; Locatelli, Claudriana; Silva, Adny H.; Conte, Aline; Chiaradia-Delatorre, Louise D.; Nunes, Ricardo J.; Yunes, Rosendo A.; Creckzynski-Pasa, Tânia B.

2014-01-01

Several obstacles are encountered in conventional chemotherapy, such as drug toxicity and poor stability. Nanotechnology is envisioned as a strategy to overcome these effects and to improve anticancer therapy. Nanoemulsions comprise submicron emulsions composed of biocompatible lipids, and present a large surface area revealing interesting physical properties. Chalcones are flavonoid precursors, and have been studied as cytotoxic drugs for leukemia cells that induce cell death by different apoptosis pathways. In this study, we encapsulated chalcones in a nanoemulsion and compared their effect with the respective free compounds in leukemia and in non-tumoral cell lines, as well as in an in vivo model. Free and loaded-nanoemulsion chalcones induced a similar anti-leukemic effect. Free chalcones induced higher toxicity in VERO cells than chalcones-loaded nanoemulsions. Similar results were observed in vivo. Free chalcones induced a reduction in weight gain and liver injuries, evidenced by oxidative stress, as well as an inflammatory response. Considering the high toxicity and the side effects induced generally by all cancer chemotherapies, nanotechnology provides some options for improving patients’ life quality and/or increasing survival rates. PMID:25264679

Real jet effects on dual jets in a crossflow

NASA Technical Reports Server (NTRS)

Schetz, J. A.

1984-01-01

A 6-ft by 6-ft wind tunnel section was modification to accommodate the 7-ft wide NASA dual-jet flate model in an effort to determine the effects of nonuniform and/or noncircular jet exhaust profiles on the pressure field induced on a nearby surface. Tests completed yield surface pressure measurements for a 90 deg circular injector producing exit profiles representative of turbofan nozzles (such as the TF-34 nozzle). The measurements were obtained for both tandem and side-by-side jet configurations, jet spacing of S/D =2, and velocity ratios of R=2.2 and 4.0. Control tests at the same mass flow rate but with uniform exit velocity profiles were also conducted, for comparison purposes. Plots for 90 deg injection and R=2.2 show that the effects of exit velocity profile nonuniformity are quite significant.

Methylphenidate Induced Lip and Tongue Biting.

PubMed

Gokcen, Cem; Karadag, Mehmet; Aksoy, Ihsan

2018-05-31

Attention deficit hyperactivity disorder (ADHD) is a life-long neurodevelopmental disorder and treatment depends on pharmacotherapy because of its biological origin. Stimulant drugs are the most commonly used treatment for ADHD and they have various side effects. Herein, we report a case who bit off the tip of her tongue with Osmotic Release Oral System methylphenidate (OROS MPH) 36 mg/day, bit the tip of her lower lip with immediate release (IR) MPH 10 mg/day and lateral part of her tongue with IR MPH 20 mg/day. A diagnosis of epilepsy was unlikely because of the normal neurological examination and electroencephalography findings. This case was considered as an atypical side effect of MPH such as perseverative/compulsive behaviours and movement disorders. Clinicians should be aware of that stimulant medications may cause lip and tongue biting behavior and this may effect treatment compliance tremendously.

The Rapalogue, CCI-779, improves salivary gland function following radiation.

PubMed

Morgan-Bathke, Maria; Harris, Zoey I; Arnett, Deborah G; Klein, Rob R; Burd, Randy; Ann, David K; Limesand, Kirsten H

2014-01-01

The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5f/f; Aqp5-Cre, Atg5+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side effects in head and neck cancer patients who have completed anti-tumor therapy.

The role of nitric oxide in the PKA inhibitor induced spatial memory deficits in rat: involvement of choline acetyltransferase.

PubMed

Najafi, Sheyda; Payandemehr, Borna; Tabrizian, Kaveh; Shariatpanahi, Marjan; Nassireslami, Ehsan; Azami, Kian; Mohammadi, Mojdeh; Asadi, Farideh; Roghani, Ali; Sharifzadeh, Mohammad

2013-08-15

Several lines of evidence show that cAMP-PKA signaling pathway plays critical role in memory functions and suggest nitric oxide as an important modulator in learning and memory. In this study, we assessed the effects of intra-hippocampal infusion of H-89, a selective PKAII inhibitor, and 1400 W, a selective inducible nitric oxide synthase (iNOS) inhibitor, on spatial memory in rats. By using the Morris water maze, spatial memory retention parameters were examined 48 h after the infusions through measuring escape latency, traveled distance, and swimming speed. The rats receiving intra-hippocampal infusions of 1400 W (100 µM/side) showed a significant reduction (*P<0.05) in escape latency and traveled distance in comparison with the control saline group. In contrast, a significant increase (**P<0.01) in escape latency and traveled distance was observed after infusion of 10 µM H-89. Moreover, among combination groups, co-administration of 1400 W (400 µM/side) with 10 µM/side of H-89 caused a significant reduction (*P<0.05) in escape latency and traveled distance in comparison with the H-89 group. Also, we evaluated the molecular effects of 1400 W on the expression of choline acetyltransferase (ChAT), a cholinergic marker, in the CA1 region of the hippocampus and medial septal area (MSA). Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400 W revealed a significant increase in ChAT immunoreactivity levels in both the CA1 and the MSA regions. Overall, the results suggest that 1400 W has protective effect against H89-induced spatial memory impairment. Moreover, the observed memory improvements caused by 1400 W infusions, might be due to interaction of iNOS with the cholinergic system. © 2013 Elsevier B.V. All rights reserved.

Bimatoprost (0.03%)-induced accommodative spasm and pseudomyopia.

PubMed

Padhy, Debananda; Rao, Aparna

2015-11-23

Bimatoprost is a prostaglandin analogue used topically in the treatment of glaucoma. Commonly known side effects include eyelash growth, iris pigmentation and conjunctival hyperemia. While pseudomyopia is reported to be caused by parasympathomimetics, such an effect precipitated by bimatoprost has not yet been reported. We report a case demonstrating pseudomyopia and accommodative spasm caused after starting bimatoprost 0.03% in a young patient with glaucoma. 2015 BMJ Publishing Group Ltd.

Efficacy of levetiracetam in primary hemifacial spasm.

PubMed

Kuroda, Takeshi; Saito, Yu; Fujita, Kazuhisa; Yano, Satoshi; Ishigaki, Seiichiro; Kato, Hirotaka; Murakami, Hidetomo; Ono, Kenjiro

2016-12-01

Hemifacial spasm (HFS) is a peripherally-induced movement disorder characterized by the involuntary, unilateral, intermittent, irregular, tonic or clonic contractions of muscles innervated by the ipsilateral facial nerve. Kindling-like hyperactivity of the facial nucleus induced by constant stimulation of compressing artery is considered as the predominant mechanism underlying the pathogenesis of HFS. As a treatment for HFS, microsurgical decompression and botulinum toxin injection have been shown to be highly successful. Anticonvulsant drugs relieve HFS in some patients; however, the use of such drugs is limited owing to their side effects, predominantly in elderly patients. We experienced two elderly HFS patients who exhibited a marked response to levetiracetam (LEV) without side effects. Although the exact underlying pharmacological mechanism remains unknown, we assume anti-kindling effect as one of the important pharmacological mechanism underlying the effect of LEV against HFS. Moreover, LEV is considered to be suitable for use in elderly patients because of its good tolerability. In addition, the lack of hepatic induction or inhibition makes it an easy and safe drug when used in addition to other anticonvulsants. Although the long-term benefit remains unknown, LEV may represent an alternative treatment for elderly HFS patients who are unable to undergo or decline surgical intervention and/or botulinum toxin injections or are intolerant to other anticonvulsants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modulation of doxorubicin-induced oxidative stress by a grape (Vitis vinifera L.) seed extract in normal and tumor cells.

PubMed

Postescu, Ion Dan; Chereches, Gabriela; Tatomir, Corina; Daicoviciu, Doina; Filip, Gabriela Adriana

2012-07-01

The major limitation of Doxorubicin (Dox) clinical use is the development of chronic and acute toxic side effects induced through the generation of reactive oxygen species. The present work was designated to investigate in vitro effects of a red grape-seed hydroethanolic extract Burgund Mare (BM), in associated administration with Dox (30 min before drug administration) in normal (Hfl-1) and tumor cell lines (HepG2 and Mls). The BM concentrations administered were below the level of the extract cytotoxiciy threshold (40 μg gallic acid [GA] Eq/mL; 37.5, 25.0, and 12.5 μg GA Eq/mL). The antioxidant capacity of the BM extract was assessed by measuring the acute toxicity at 24 h, lipid peroxides (LP), and protein oxidation. In normal cells, the product statistically decreased cytotoxicity and markedly inhibited LP and protein carbonyl (PC) formation, in a dose-dependent relationship. On contrary, in tumor cells, such treatment resulted in a reversed effect, cell death, malondialdehyde, and PC contents increasing with BM dose enhancement. BM extract treatment prior to subsequent administration of Dox afforded a differential protection against Dox-negative toxic side effects in normal cells without weakening (even enhancing) Dox's antitumor activity.

Collection of gravitropic effectors from mucilage of electrotropically-stimulated roots of Zea mays L

NASA Technical Reports Server (NTRS)

Fondren, W. M.; Moore, R.

1987-01-01

We placed agar blocks adjacent to tips of electrotropically stimulated primary roots of Zea mays. Blocks placed adjacent to the anode-side of the roots for 3 h induced significant curvature when subsequently placed asymmetrically on tips of vertically-oriented roots. Curvature was always toward the side of the root unto which the agar block was placed. Agar blocks not contacting roots and blocks placed adjacent to the cathode-side of electrotropically stimulated roots did not induce significant curvature when placed asymmetrically on tips of vertically-oriented roots. Atomic absorption spectrophotometry indicated that blocks adjacent to the anode-side of electrotropically-stimulated roots contained significantly more calcium than (1) blocks not contacting roots, and (2) blocks contacting the cathode-side of roots. These results demonstrate the presence of a gradient of endogenous Ca in mucilage of electrotropically-stimulated roots (i.e. roots undergoing gravitropic-like curvature).

Origins of pressure-induced protein transitions.

PubMed

Chalikian, Tigran V; Macgregor, Robert B

2009-12-18

The molecular mechanisms underlying pressure-induced protein denaturation can be analyzed based on the pressure-dependent differences in the apparent volume occupied by amino acids inside the protein and when they are exposed to water in an unfolded conformation. We present here an analysis for the peptide group and the 20 naturally occurring amino acid side chains based on volumetric parameters for the amino acids in the interior of the native state, the micelle-like interior of the pressure-induced denatured state, and the unfolded conformation modeled by N-acetyl amino acid amides. The transfer of peptide groups from the protein interior to water becomes increasingly favorable as pressure increases. Thus, solvation of peptide groups represents a major driving force in pressure-induced protein denaturation. Polar side chains do not appear to exhibit significant pressure-dependent changes in their preference for the protein interior or solvent. The transfer of nonpolar side chains from the protein interior to water becomes more unfavorable as pressure increases. We conclude that a sizeable population of nonpolar side chains remains buried inside a solvent-inaccessible core of the pressure-induced denatured state. At elevated pressures, this core may become packed almost as tightly as the interior of the native state. The presence and partial disappearance of large intraglobular voids is another driving force facilitating pressure-induced denaturation of individual proteins. Our data also have implications for the kinetics of protein folding and shed light on the nature of the folding transition state ensemble.

Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy.

PubMed

Brazill, Jennifer M; Cruz, Beverley; Zhu, Yi; Zhai, R Grace

2018-06-12

Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side effect of many commonly used chemotherapeutic agents, including paclitaxel. Currently, there are no neuroprotective or effective symptomatic treatments for CIPN. Lack of understanding of the in vivo mechanisms of CIPN has greatly impeded the identification of therapeutic targets. Here, we optimized a model of paclitaxel-induced peripheral neuropathy using Drosophila larvae that recapitulates aspects of chemotherapy-induced sensory dysfunction . We showed that nociceptive sensitivity is associated with disrupted organization of microtubule-associated MAP1B/Futsch and aberrant stabilization of peripheral sensory dendrites. These findings establish a robust and amenable model for studying peripheral mechanisms of CIPN. Using this model, we uncovered a critical role for nicotinamide mononucleotide adenylyltransferase (Nmnat) in maintaining the integrity and function of peripheral sensory neurons and uncovered Nmnat's therapeutic potential against diverse sensory symptoms of CIPN. © 2018. Published by The Company of Biologists Ltd.

Antioxidant properties of MDL and MMDL, two nicergoline metabolites, during chronic administration of haloperidol.

PubMed

Vairetti, Mariapia; Battaglia, Angelo; Carfagna, Nicola; Luigi Canonico, Pier; Bertè, Francantonio; Richelmi, Plinio

2002-10-18

We evaluated the effects of 10-alpha-methoxy-9,10-dihydrolysergol (MDL) and 1-methyl-10-alpha-methoxy-9,10-dihydrolysergol (MMDL), two nicergoline metabolites, during chronic treatment with haloperidol in rats. Haloperidol induced a significant decrease in the glutathione (GSH) content in selected areas of the brain and in the liver. Prolonged administration of MDL, MMDL or nicergoline antagonized the haloperidol-induced GSH decrease. Lipid peroxidation in the cortex and striatum was suppressed by MDL, MMDL or nicergoline administration. Our results show that MDL, MMDL and nicergoline have antioxidant activity, preventing not only GSH depletion but also lipid peroxidation. These observations suggest beneficial properties of MDL and MMDL in the treatment of neuroleptic-induced side effects. Copyright 2002 Elsevier Science B.V.

Hand-foot syndrome in a patient with metastatic lung adenocarcinoma induced by high-dose icotinib: A case report and review of the literature.

PubMed

Zheng, Yulong; Fang, Weijia; Xu, Nong

2012-12-01

Icotinib is a new oral epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI). The most frequent side-effects of icotinib include rash and diarrhea. Hand-foot syndrome (HFS) induced by EGFR-TKI is rare. The present study describes, for the first time, HFS induced by high-dose icotinib in a 65-year old female with metastatic lung adenocarcinoma. The patient developed HFS during the first week of icotinib treatment with characteristic clinical presentation. HFS regressed after icotinib dose-reduction was initiated. HFS may occur with icotinib, especially when administered in high doses.

Chloroform-induced insanity defence confounds lawyer Lincoln.

PubMed

Spiegel, A D; Suskind, P B

1997-12-01

During an 1857 trial, the defence claimed that the accused should be absolved of wilful murder because an overdose of chloroform during surgery induced insanity. In a rare appearance as a prosecutor, Abraham Lincoln tried the case for the State of Illinois. Expert medical witnesses testified about the side effects of chloroform and chloroform-induced insanity. Significantly, Lincoln was not knowledgeable about medical jurisprudence and overlooked potential sources of evidence and expert witnesses. Defence lawyers presented an impressive array of physicians to testify about insanity, about chloroform and about the results of an overdosage during anaesthesia. Considering the state of scientific knowledge at the time, the trial was notable.

An integrated view of cisplatin-induced nephrotoxicity and ototoxicity

PubMed Central

Karasawa, Takatoshi; Steyger, Peter S.

2015-01-01

Cisplatin is one of the most widely-used drugs to treat cancers. However, its nephrotoxic and ototoxic side-effects remain major clinical limitations. Recent studies have improved our understanding of the molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. While cisplatin binding to DNA is the major cytotoxic mechanism in proliferating (cancer) cells, nephrotoxicity and ototoxicity appear to result from toxic levels of reactive oxygen species and protein dysregulation within various cellular compartments. In this review, we discuss molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. We also discuss potential clinical strategies to prevent nephrotoxicity and ototoxicity and their current limitations. PMID:26101797

Effect of fronto-orbital advancement on astigmatism in patients with anterior plagiocephaly.

PubMed

Song, Hyun Beom; Yang, Hee Kyung; Baek, Rong-Min; Hwang, Jeong-Min; Kim, Namju; Wang, Kyu-Chang; Kim, Sukwha

2016-10-01

The purpose of this study was to determine the effect of unilateral fronto-orbital advancement (FOA) or bilateral FOA on ocular aspects of plagiocephaly. A retrospective review of ocular findings in 16 patients with plagiocephaly was performed. Patients were divided into 2 groups: 12 patients who underwent bilateral FOA (bFOA) and 4 patients who underwent unilateral FOA (uFOA), and ocular findings were compared. One-half of patients showed strabismus in both groups, and all had exotropia. Hypertropia was found only on the same side of the plagiocephaly in 17% of the bFOA group and 25% of the uFOA group. One-third of the patients in the bFOA group and one-half of patients in the uFOA group had oblique muscle dysfunction. In terms of astigmatism, the degree of with-the-rule astigmatism on the contralateral side was larger in the bFOA group compared to the uFOA group (p = 0.030). The degree of with-the-rule astigmatism was larger on the contralateral side than the ipsilateral side (p = 0.005) in the bFOA group. Patients with abnormalities in ductions/versions had larger astigmatism on the contralateral side than those without abnormalities in ductions/versions. In conclusion, bilateral FOA could induce unwanted outcomes of larger astigmatism on the contralateral side. Astigmatism should be carefully evaluated after bilateral FOA. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

The combined use of oral medroxyprogesterone acetate and methyltestosterone in a male contraceptive trial programme.

PubMed

Bain, J; Rachlis, V; Robert, E; Khait, Z

1980-04-01

A male contraceptive trial was undertaken in 23 men using a combination of oral medroxyprogesterone acetate (MPA) and oral methyltestosterone (MeT). The men were divided into four groups according to varying drug dosages and were followed for 15 months (control - 3 months, treatment - 6 months, follow-up - 6 months). The parameters assessed included sperm count and motility, serum gonadotropins and sex steroids, and several biochemical and hematological tests. A questionnaire dealing with side-effects and changes in sexual function was administered intermittently. Although sperm count was suppressed (most dramatically at the highest drug doses, MPA 20mg,MeT 20mg), it was not suppressed to infertile levels. Sperm motility was unaltered; LH was modestly suppressed, FSH was not suppressed; testosterone was suppressed even at low doses; dihydrotestosterone responses were inconsistent. No significant biochemical abnormalities or side-effects occurred although some men experienced mild transient acne, gynecomastia and decreased testicular size. We conclude that in the doses used in this trial, the combination of MPA and MeT is not effective for male contraceptive, purposes and that higher doses may induce severe and undesirable side-effects.

Drug safety evaluation of dronedarone in atrial fibrillation.

PubMed

De Ferrari, Gaetano M; Dusi, Veronica

2012-11-01

Dronedarone was developed with the intent of replicating the antiarrhythmic effects of amiodarone, while minimizing its side effects. Side effects reported in eight randomized clinical trials are discussed, comparing dronedarone and placebo (DAFNE, EURIDIS, ADONIS, ERATO, ANDROMEDA, ATHENA, PALLAS, total number of patients treated with dronedarone 5347), or dronedarone and amiodarone (DIONYSOS, total number of patients treated with dronedarone 249). The results of the first trials, including ATHENA, set high expectations by suggesting that dronedarone may decrease the risk of hospitalization (and even cardiovascular mortality) among patients with paroxysmal and persistent atrial fibrillation (AF), and that it could be regarded as an easy-to-use drug that could be prescribed by general practitioners; unfortunately, dronedarone has not met these expectations. Dronedarone may increase mortality and heart failure hospitalization in patients with advanced NYHA class and in patients with permanent AF, preventing its use in these settings. In addition to gastrointestinal side effects that may lead to discontinuation in 5 - 10% of patients, dronedarone may induce very rare but severe liver and lung toxicity. Despite these limitations and its relatively limited antiarrhythmic potency, dronedarone may still be a useful drug for well-selected patients.

Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation: proof of concept and application to the pyramidal tract side effect induced by pallidal stimulation.

PubMed

Baumgarten, Clement; Zhao, Yulong; Sauleau, Paul; Malrain, Cecile; Jannin, Pierre; Haegelen, Claire

2016-04-01

Deep brain stimulation of the medial globus pallidus (GPm) is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning-based method called PyMAN (PTSE model based on artificial neural network) accounting for the current used in stimulation, the three-dimensional electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the GPm have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was 0.78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

Eicosapentaenoic acid attenuates dexamethasome-induced apoptosis by inducing adaptive autophagy via GPR120 in murine bone marrow-derived mesenchymal stem cells

PubMed Central

Gao, B; Han, Y-H; Wang, L; Lin, Y-J; Sun, Z; Lu, W-G; Hu, Y-Q; Li, J-Q; Lin, X-S; Liu, B-H; Jie, Q; Yang, L; Luo, Z-J

2016-01-01

Long-term use of glucocorticoids is a widespread clinical problem, which currently has no effective solution other than discontinuing the use. Eicosapentaenoic acid (EPA), an omega-3 long chain polyunsaturated fatty acid (n-3 PUFA), which is largely contained in fish or fish oil, has been reported to promote cell viability and improve bone metabolism. However, little is known about the effects of EPA on dexamethasome (Dex)-induced cell apoptosis. In this study, we showed that EPA-induced autophagy of murine bone marrow-derived mesenchymal stem cells (mBMMSCs). Meanwhile, EPA, but not arachidonic acid (AA), markedly inhibited Dex-induced apoptosis and promoted the viability of mBMMSCs. We also observed that EPA-induced autophagy was modulated by GPR120, but not GPR40. Further experiments showed that the mechanism of EPA-induced autophagy associated with GPR120 modulation involved an increase in the active form of AMP-activated protein kinase and a decrease in the activity of mammalian target of RAPA. The protective effect of EPA on Dex-induced apoptosis via GPR120-meditated induction of adaptive autophagy was supported by in vivo experiments. In summary, our findings may have important implications in developing future strategies to use EPA in the prevention and therapy of the side effects induced by long-term Dex-abuse. PMID:27228350

Propofol inhibits carbachol-induced chloride secretion by directly targeting the basolateral K+ channel in rat ileum epithelium.

PubMed

Tang, S-H; Wang, H-Y; Sun, H; An, N; Xiao, L; Sun, Q; Zhao, D-B

2017-02-01

Propofol is a widely used intravenous general anesthetic. Acetylcholine (ACh) is critical in controlling epithelial ion transport. This study was to investigate the effects of propofol on ACh-evoked secretion in rat ileum epithelium. The Ussing chamber technique was used to investigate the effects of propofol on carbachol (CCh)-evoked short-circuit currents (Isc). Propofol (10 -2 -10 -6  mol/L) attenuated CCh-evoked Isc of rat ileum mucosa in a dose-dependent manner. The inhibitory effect of propofol was only evident after application to the serosal side. Pretreatment with tetrodotoxin (TTX, 0.3 μmol/L, n=5) had no effect on propofol-induced inhibitory effect, whereas serosal application of K + channel inhibitor, glibenclamide, but not, an ATP-sensitive K + channel inhibitor, largely reduced the inhibitory effect of propofol. In addition, pretreatment with either hexamethonium bromide (HB, nicotinic nACh receptor antagonist) or Cl - channel blockers niflumic acid and cystic fibrosis transmembrane conductance regulator (inh)-172 did not produce any effect on the propofol-induced inhibitory effect. Propofol inhibits CCh-induced intestinal secretion by directly targeting basolateral K + channels. © 2016 John Wiley & Sons Ltd.

Pharmacological Modulation of the Mitochondrial Electron Transport Chain in Paclitaxel-Induced Painful Peripheral Neuropathy.

PubMed

Griffiths, Lisa A; Flatters, Sarah J L

2015-10-01

Paclitaxel is an effective first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Mitochondrial dysfunction and oxidative stress have been implicated in paclitaxel-induced painful neuropathy. Here we show the effects of pharmacological modulation of mitochondrial sites that produce reactive oxygen species using systemic rotenone (complex I inhibitor) or antimycin A (complex III inhibitor) on the maintenance and development of paclitaxel-induced mechanical hypersensitivity in adult male Sprague Dawley rats. The maximally tolerated dose (5 mg/kg) of rotenone inhibited established paclitaxel-induced mechanical hypersensitivity. However, some of these inhibitory effects coincided with decreased motor coordination; 3 mg/kg rotenone also significantly attenuated established paclitaxel-induced mechanical hypersensitivity without any motor impairment. The maximally tolerated dose (.6 mg/kg) of antimycin A reversed established paclitaxel-induced mechanical hypersensitivity without any motor impairment. Seven daily doses of systemic rotenone or antimycin A were given either after paclitaxel administration or before and during paclitaxel administration. Rotenone had no significant effect on the development of paclitaxel-induced mechanical hypersensitivity. However, antimycin A significantly inhibited the development of paclitaxel-induced mechanical hypersensitivity when given before and during paclitaxel administration but had no effect when given after paclitaxel administration. These studies provide further evidence of paclitaxel-evoked mitochondrial dysfunction in vivo, suggesting that complex III activity is instrumental in paclitaxel-induced pain. This study provides further in vivo evidence that mitochondrial dysfunction is a key contributor to the development and maintenance of chemotherapy-induced painful neuropathy. This work also indicates that selective modulation of the electron transport chain can induce antinociceptive effects in a preclinical model of paclitaxel-induced pain. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Aripiprazole-Induced Hyperlipidemia: An Update.

PubMed

Tarraf, Caroline; Naja, Wadih J

2016-08-25

To review the literature on the metabolic side effects of aripiprazole. Three cases of aripiprazole-induced hypertriglyceridemia are also presented. A search was conducted of English-language articles and abstracts (meta-analyses, randomized controlled trials, clinical trials, naturalistic open-label trials, reviews, and case reports) published up to August 31, 2014, in electronic databases (PubMed, MEDLINE). Free-text and MeSH search keywords included aripiprazole, cholesterol, triglyceride, lipid profile, hyperlipidemia, and hypercholesterolemia and their differing terminations and combinations. The search was supplemented by a manual review of reference lists from the identified publications. Pediatric studies were excluded. Twenty-two articles were found and 3 aspects of the metabolic side effects of aripiprazole were reviewed: (1) the prevalence of the metabolic syndrome in mentally ill patients prior to any antipsychotic use to highlight the initial predisposition of this group of patients to develop the metabolic syndrome, (2) the prevalence of metabolic changes depending on the choice of antipsychotic (aripiprazole compared to other antipsychotics), and (3) metabolic changes reported after switching from an antipsychotic to aripiprazole. Patients with mental disorders are at high risk for developing dyslipidemia, diabetes, and the full criteria of the metabolic syndrome. Antipsychotic use exacerbates this risk, thus increasing the mortality in this population. Nevertheless, it seems that the risk for these side effects varies with each antipsychotic. Although by and large the literature supports the supposition that aripiprazole causes less metabolic effects than other antipsychotics, we report 3 cases of serious aripiprazole-related dyslipidemia in young subjects. On the basis of these 3 cases, aripiprazole can cause hypertriglyceridemia. Triglyceride levels should be carefully monitored in patients with mental disorders taking aripiprazole. © Copyright 2016 Physicians Postgraduate Press, Inc.

Anti-kindling Induced by Two-Stage Coordinated Reset Stimulation with Weak Onset Intensity

PubMed Central

Zeitler, Magteld; Tass, Peter A.

2016-01-01

Abnormal neuronal synchrony plays an important role in a number of brain diseases. To specifically counteract abnormal neuronal synchrony by desynchronization, Coordinated Reset (CR) stimulation, a spatiotemporally patterned stimulation technique, was designed with computational means. In neuronal networks with spike timing–dependent plasticity CR stimulation causes a decrease of synaptic weights and finally anti-kindling, i.e., unlearning of abnormally strong synaptic connectivity and abnormal neuronal synchrony. Long-lasting desynchronizing aftereffects of CR stimulation have been verified in pre-clinical and clinical proof of concept studies. In general, for different neuromodulation approaches, both invasive and non-invasive, it is desirable to enable effective stimulation at reduced stimulation intensities, thereby avoiding side effects. For the first time, we here present a two-stage CR stimulation protocol, where two qualitatively different types of CR stimulation are delivered one after another, and the first stage comes at a particularly weak stimulation intensity. Numerical simulations show that a two-stage CR stimulation can induce the same degree of anti-kindling as a single-stage CR stimulation with intermediate stimulation intensity. This stimulation approach might be clinically beneficial in patients suffering from brain diseases characterized by abnormal neuronal synchrony where a first treatment stage should be performed at particularly weak stimulation intensities in order to avoid side effects. This might, e.g., be relevant in the context of acoustic CR stimulation in tinnitus patients with hyperacusis or in the case of electrical deep brain CR stimulation with sub-optimally positioned leads or side effects caused by stimulation of the target itself. We discuss how to apply our method in first in man and proof of concept studies. PMID:27242500

Tailoring the Employment of Offshore Wind Turbine Support Structure Load Mitigation Controllers

NASA Astrophysics Data System (ADS)

Shrestha, Binita; Kühn, Martin

2016-09-01

The currently available control concepts to mitigate aerodynamic and hydrodynamic induced support structure loads reduce either fore-aft or side-to-side damage under certain operational conditions. The load reduction is achieved together with an increase in loads in other components of the turbine e.g. pitch actuators or drive train, increasing the risk of unscheduled maintenance. The main objective of this paper is to demonstrate a methodology for reduction of support structure damage equivalent loads (DEL) in fore-aft and side-to-side directions using already available control concepts. A multi-objective optimization problem is formulated to minimize the DELs, while limiting the collateral effects of the control algorithms for load reduction. The optimization gives trigger values of sea state condition for the activation or deactivation of certain control concepts. As a result, by accepting the consumption of a small fraction of the load reserve in the design load envelope of other turbine components, a considerable reduction of the support structure loads is facilitated.

Assimilative and non-assimilative color spreading in the watercolor configuration.

PubMed

Kimura, Eiji; Kuroki, Mikako

2014-01-01

A colored line flanking a darker contour will appear to spread its color onto an area enclosed by the line (watercolor effect). The watercolor effect has been characterized as an assimilative effect, but non-assimilative color spreading has also been demonstrated in the same spatial configuration; e.g., when a black inner contour (IC) is paired with a blue outer contour (OC), yellow color spreading can be observed. To elucidate visual mechanisms underlying these different color spreading effects, this study investigated the effects of luminance ratio between the double contours on the induced color by systematically manipulating the IC and the OC luminance (Experiment 1) as well as the background luminance (Experiment 2). The results showed that the luminance conditions suitable for assimilative and non-assimilative color spreading were nearly opposite. When the Weber contrast of the IC to the background luminance (IC contrast) was smaller in size than that of the OC (OC contrast), the induced color became similar to the IC color (assimilative spreading). In contrast, when the OC contrast was smaller than or equal to the IC contrast, the induced color became yellow (non-assimilative spreading). Extending these findings, Experiment 3 showed that bilateral color spreading, i.e., assimilative spreading on one side and non-assimilative spreading on the other side, can also be observed in the watercolor configuration. These results suggest that the assimilative and the non-assimilative spreading were mediated by different visual mechanisms. The properties of the assimilative spreading are consistent with the model proposed to account for neon color spreading (Grossberg and Mingolla, 1985) and extended for the watercolor effect (Pinna and Grossberg, 2005). However, the present results suggest that additional mechanisms are needed to account for the non-assimilative color spreading.

Motility changes induced by intraluminal FeSO4 in guinea pig jejunum.

PubMed

Wang, K; Bertrand, R L; Senadheera, S; Polglaze, K E; Murphy, T V; Sandow, S L; Liu, L; Bornstein, J C; Bertrand, P P

2014-03-01

Dietary iron supplementation is associated with gastrointestinal (GI) side effects including vomiting, nausea, and diarrhea. Although inorganic iron in high concentrations may be damaging to the intestinal mucosa, we hypothesize that there are physiological effects on the GI tract that occur at concentrations achieved by supplementation. Thus, our aim was to investigate the effect of intraluminal ferrous sulfate (FeSO4 ) on jejunal motility. Segments of guinea pig jejunum were cannulated and the intraluminal pressure recorded with a transducer, while movements were recorded with a video camera. Peristaltic threshold was the oral pressure that evoked four consecutive propulsive contractions. The nutrients decanoic acid (1 mM), l-phenylalanine (50 mM), or the micronutrient FeSO4 (1 mM) were infused intraluminally. We also tested the effect of FeSO4 on electrochemically detected serotonin (5-HT, 5-hydroxytryptamine) released from in vitro tissues, both at rest and following mechanical stimulation. The jejuna peristaltic threshold was significantly decreased by all three nutrients: FeSO4 : 31 ± 2-23 ± 3 mmH2 O; decanoic acid: 27 ± 2-14 ± 2 mmH2 O; and l-phenylalanine: 30 ± 3-14 ± 3mmH2 O. Of the three, only decanoic acid induced segmentation, while FeSO4 inhibited decanoic acid-induced segmentation. Resting 5-HT release was increased by FeSO4 (128% of control), but mechanically evoked 5-HT release was reduced (70% of control). These data suggest that some luminal effects of inorganic iron on jejunal motility could be mediated through a pathway involving altered release of 5-HT. A better understanding of the interaction between luminal iron and 5-HT containing enterochromaffin cells could improve iron supplementation strategies, thus reducing side effects. © 2013 John Wiley & Sons Ltd.

Effect of administrating polysaccharide from black currant (Ribes nigrum L.) on atopic dermatitis in NC/Nga mice.

PubMed

Ashigai, Hiroshi; Komano, Yuta; Wang, Guanying; Kawachi, Yasuji; Sunaga, Kazuko; Yamamoto, Reiko; Takata, Ryoji; Miyake, Mika; Yanai, Takaaki

2018-01-01

Atopic dermatitis (AD) is a chronic inflammatory skin disease that causes dry skin and functional disruption of the skin barrier. AD is often accompanied by allergic inflammation. AD patient suffer from heavy itching, and their quality of life is severely affected. Some pharmaceuticals for AD have some side effects such as skin atrophy. So it is necessary to develop mild solutions such as food ingredients without side effects. There are various causes of AD. It is especially induced by immunological imbalances such as IFN-γ reduction. IFN-γ has an important role in regulating IgE, which can cause an allergy reaction. NC/Nga mice develop AD and IgE hyperproduction. In a previous study, we revealed that administration of polysaccharide from black currant ( R. nigrum ) has an effect on immunomodulation. It induces IFN-γ production from myeloid dendritic cells. We named this polysaccharide cassis polysaccharide (CAPS). In this report, we studied the effect of administering CAPS on atopic dermatitis in NC/Nga mice. Thirty NC/Nga mice that developed symptoms of atopic dermatitis were used. We divided them into three groups (control, CAPS administration 12 mg/kg/day, CAPS administration 60 mg/kg/day). For 4 weeks, we evaluated clinical score, serum IgE levels, gene expression of spleen, and skin pathology. We revealed that CAPS administration improves atopic dermatitis symptoms. We also found that CAPS administration suppresses IgE hyperproduction and induces IFN-γ gene transcription in the spleen. Finally, we confirmed that CAPS administration suppresses mast cell migration to epidermal skin. These results indicated that CAPS has an effect on AD.

Anti-platelet and anti-thrombotic effect of a traditional herbal medicine Kyung-Ok-Ko.

PubMed

Kim, Tae-Ho; Lee, Kyoung Mee; Hong, Nam Doo; Jung, Yi-Sook

2016-02-03

Kyung-Ok-Ko (KOK), a traditional herbal prescription, contains six main ingredients; Rehmannia glutinosa var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey. KOK has been widely taken as a traditional oriental medicine for improving blood circulation or age-related symptoms, such as dementia and stroke. However, the effect of KOK on platelet activity has not been clarified. To evaluate the effect of KOK on platelet function, we evaluated its effect on functional markers of platelet activation such as aggregation and shape change. As a mechanism study for the effect of KOK, we examined its effect on granule secretion, intracellular Ca(2+) increase, and PLCγ and Akt activation. To investigate the effect of orally administered KOK (0.5, 1, 2 g/kg), we examined its ex vivo effect on platelet aggregation in rat, and its in vivo anti-thrombotic effect in mice thromboembolism model. Furthermore, the effect of KOK on bleeding time was examined to estimate its potential side effect. KOK (0.3, 1, 3, 10 mg/ml) inhibited collagen-induced platelet aggregation and shape change in rat platelets in a concentration-dependent manner. The mechanism for the anti-platelet effect of KOK seems to involve the inhibition of ATP release, intracellular Ca(2+) elevation, and the phosphorylation of PLCγ and Akt. In rat ex vivo study, KOK (2 g/kg, p.o. for 1 day, and 0.5, 1, 2 g/kg, p.o. for 7 days) also had significant inhibitory effects on collagen-induced platelet aggregation. In addition, KOK showed a significant protective effect against thrombosis attack in mice. The prolongation of bleeding time by KOK was much less than that by ASA, suggesting a beneficial potential of KOK than ASA in view of side effect. These findings suggest that KOK elicits remarkable anti-platelet and anti-thrombotic effects with less side effect of bleeding, and therefore, it may have a therapeutic potential for the prevention of platelet-associated cardiovascular diseases. Copyright © 2015. Published by Elsevier Ireland Ltd.

Side-detecting optical fiber coated with Zn(OH)2 nanorods for ultraviolet sensing applications

NASA Astrophysics Data System (ADS)

Azad, S.; Parvizi, R.; Sadeghi, E.

2017-09-01

This paper presents an improved coupling efficiency and side detecting of UV radiation induced by light scattering and luminescent features of Zn(OH)2 nanorods coated multimode optical fibers. Uniform and high density Zn(OH)2 nanorods were grown hydrothermally on the core of chemically etched multimode optical fibers. The prepared samples were characterized through x-ray diffraction patterns, scanning electron microscopy and photoluminescence spectroscopy. The detecting technique was based on the intensity modulation of the side coupled light through the Zn(OH)2 nanorods. A simple and cost-effective UV radiation detecting setup has been designed. Experimentally estimated coupling efficiency of the proposed setup was obtained near 11%. The proposed device exhibited stable and reversible responses with a fast rising and decaying time of about 1.4 s and 0.85 s, respectively.

Activation of β-adrenoceptors in the bed nucleus of the stria terminalis induces food intake reduction and anxiety-like behaviors.

PubMed

Naka, Tomonori; Ide, Soichiro; Nakako, Tomokazu; Hirata, Mikie; Majima, Yuki; Deyama, Satoshi; Takeda, Hiroshi; Yoshioka, Mitsuhiro; Minami, Masabumi

2013-04-01

We previously demonstrated the critical role of noradrenergic transmission within the ventral part of the bed nucleus of the stria terminalis (vBNST) in pain-induced aversion. We showed that activation of β-adrenoceptors in this brain region by intra-vBNST injection of isoproterenol, a β-adrenoceptor agonist, produced aversive responses. In the present study, we examined the effects of a β-adrenoceptor agonist injected into the vBNST on food intake and anxiety-like behaviors in male Sprague-Dawley rats. Bilateral intra-vBNST injection of isoproterenol (3 and 10 nmol/side) caused a dose-dependent decrease in food intake; this suppressive effect was reversed by co-administration of timolol, a β-adrenoceptor antagonist. Dose-dependent (10 and 30 nmol/side) induction of anxiety-like behaviors by isoproterenol was observed in the elevated plus maze (EPM) test, which was also reversed by co-administration of timolol. Off-site control injections of isoproterenol into the lateral ventricle did not show any significant effect in the food consumption and EPM tests. These results suggest that the vBNST is one of the neuroanatomical substrates which may be involved in the close relationship between negative affective states and reduction of food intake, and that noradrenergic transmission within this brain region plays a critical role in inducing anxiety-like behaviors and reduced food intake. Copyright © 2012 Elsevier Ltd. All rights reserved.

Niclosamide inhibits leaf blight caused by Xanthomonas oryzae in rice

PubMed Central

Kim, Sung-Il; Song, Jong Tae; Jeong, Jin-Yong; Seo, Hak Soo

2016-01-01

Rice leaf blight, which is caused by the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), results in huge losses in grain yield. Here, we show that Xoo-induced rice leaf blight is effectively controlled by niclosamide, an oral antihelminthic drug and molluscicide, which also functions as an anti-tumor agent. Niclosamide directly inhibited the growth of the three Xoo strains PXO99, 10208 and K3a. Niclosamide moved long distances from the site of local application to distant rice tissues. Niclosamide also increased the levels of salicylate and induced the expression of defense-related genes such as OsPR1 and OsWRKY45, which suppressed Xoo-induced leaf wilting. Niclosamide had no detrimental effects on vegetative/reproductive growth and yield. These combined results indicate that niclosamide can be used to block bacterial leaf blight in rice with no negative side effects. PMID:26879887

Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract of Equisetum arvense.

PubMed

Kour, Jasbir; Ali, Md Niamat; Ganaie, Hilal Ahmad; Tabassum, Nahida

2017-01-01

In the present study, we evaluated the potential of the plant E. arvense against the cytotoxic and mutagenic effects induced by cyclophosphamide (chemotherapeutic agent) in the bone marrow cells of mice using the Chromosome assay (CA) and Mitotic index (MI) in vivo as the biomarkers. The study was performed following 3 protocols: pre-treatment, simultaneous treatment and post-treatment with the ethanolic extract of the plant. The results demonstrated that the plant extract was not cytotoxic and mutagenic and has a protective effect against the mutagenicity induced by cyclophosphamide in pre, simultaneous and post treatments and against its cytotoxicity as well. Because of its ability to prevent chromosomal damage , E. arvense is likely to open an interesting field concerning its possible use in clinical applications, most importantly in cancer as a chemopreventive agent or even as a coadjuvant to chemotherapy to reduce the side effects associated with it.

Hesperetin-5,7,3'-O-triacetate suppresses airway hyperresponsiveness in ovalbumin-sensitized and challenged mice without reversing xylazine/ketamine-induced anesthesia in normal mice.

PubMed

Yang, You-Lan; Chen, Chi-Li; Chen, Chi-Ming; Ko, Wun-Chang

2017-05-30

We recently reported that hesperetin-5,7,3'-O-triacetate (HTA) dually inhibited phosphodiesterase (PDE)3/4 with a therapeutic ratio of 20.8. The application and development of PDE4 inhibitors for treating asthma or COPD are limited by their side effects, such as nausea, vomiting and gastric hypersecretion. PDE4 inhibitors were reported to reverse xylazine/ketamine-induced anesthesia in rats and triggered vomiting in ferrets. Thus the reversing effect of HTA on xylazine/ketamine-induced anesthesia in mice was studied to assess emetic effect of HTA. The aim of this study was to prove the therapeutic effect of HTA without vomiting effect at an effective dose for treating COPD. Ten female BALB/c mice in each group were sensitized by ovalbumin (OVA) on days 0 and 14. On day 21, these mice were emphasized the sensitization by Freund's complete adjuvant. Mice were challenged by 1% OVA nebulization on days 28, 29, and 30. Airway hyperresponsiveness (AHR) was assessed on day 32 in each group, using the FlexiVent system to determine airway resistance (R L ) and lung dynamic compliance (C dyn ) in anesthetized ovalbumin (OVA)-sensitized and challenged mice. Each group was orally administered HTA (10 ~ 100 μmol/kg), roflumilast (1 and 5 mg/kg) or vehicles (controls) 2 h before and 6 and 24 h after OVA provocation. For comparison, sham-treated mice were challenged with saline instead of 1% OVA. The ability to reverse xylazine/ketamine-induced anesthesia by HTA or roflumilast for 3 h was determined in normal mice. We used roflumilast, a selective PDE4 inhibitor and bronchodilator for severe COPD approved by the US Food and Drug Administration, as a reference drug. In the results, HTA (100 μmol/kg, p.o.) or roflumilast (5 mg/kg, p.o.) significantly suppressed all R L values of MCh at 0.78 ~ 25 mg/mL and enhanced C dyn values of MCh at 3.125 ~ 25 mg/mL compared to OVA-sensitized and -challenged control mice. Orally administered 1, 3 or 10 mg/kg roflumilast, but not 30 or 100 μmol/kg HTA, significantly reversed xylazine/ketamine-induced anesthesia. In contrast to roflumilast, HTA may ameliorate COPD but induce few side effects of nausea, vomiting and gastric hypersecretion at an effective dose for treating COPD, because HTA did not reverse xylazine/ketamine-induced anesthesia in mice.

Tuning the thermal conductivity of solar cell polymers through side chain engineering.

PubMed

Guo, Zhi; Lee, Doyun; Liu, Yi; Sun, Fangyuan; Sliwinski, Anna; Gao, Haifeng; Burns, Peter C; Huang, Libai; Luo, Tengfei

2014-05-07

Thermal transport is critical to the performance and reliability of polymer-based energy devices, ranging from solar cells to thermoelectrics. This work shows that the thermal conductivity of a low band gap conjugated polymer, poly(4,8-bis-alkyloxybenzo[1,2-b:4,5-b']dithiophene-2,6-diyl-alt-(alkylthieno[3,4-b]thiophene-2-carboxylate)-2,6-diyl) (PBDTTT), for photovoltaic applications can be actively tuned through side chain engineering. Compared to the original polymer modified with short branched side chains, the engineered polymer using all linear and long side chains shows a 160% increase in thermal conductivity. The thermal conductivity of the polymer exhibits a good correlation with the side chain lengths as well as the crystallinity of the polymer characterized using small-angle X-ray scattering (SAXS) experiments. Molecular dynamics simulations and atomic force microscopy are used to further probe the molecular level local order of different polymers. It is found that the linear side chain modified polymer can facilitate the formation of more ordered structures, as compared to the branched side chain modified ones. The effective medium theory modelling also reveals that the long linear side chain enables a larger heat carrier propagation length and the crystalline phase in the bulk polymer increases the overall thermal conductivity. It is concluded that both the length of the side chains and the induced polymer crystallization are important for thermal transport. These results offer important guidance for actively tuning the thermal conductivity of conjugated polymers through molecular level design.

Drug-Induced Hematologic Syndromes

PubMed Central

Mintzer, David M.; Billet, Shira N.; Chmielewski, Lauren

2009-01-01

Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. PMID:19960059

Flavonoids, the emerging dietary supplement against cisplatin-induced nephrotoxicity.

PubMed

Athira, K V; Madhana, Rajaram Mohanrao; Lahkar, Mangala

2016-03-25

The letter illustrates the emerging potential of flavonoids as dietary supplement to ameliorate cisplatin-induced nephrotoxicity and refers to the recent article on ''Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat'' by Chtourou et al. They demonstrated that supplementation of naringin, a flavanone glycoside, found in grape and citrus fruit species, can attenuate cisplatin-induced renal dysfunction via restoration of redox balance and suppression of inflammation, NF-κB activation and apoptosis. The chemotherapeutic efficacy of cisplatin has always compelled the researchers to find solution to ameliorate its side effects. In recent years, numerous candidates have been evaluated for their protective potential against cisplatin-induced nephrotoxicity and flavonoids have come up with promising results. The future prospects might be promising with a proper refinement and collective integration of the preclinical and clinical research in the field of flavonoid supplementation to cisplatin therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neutral beam and ICP etching of HKMG MOS capacitors: Observations and a plasma-induced damage model

NASA Astrophysics Data System (ADS)

Kuo, Tai-Chen; Shih, Tzu-Lang; Su, Yin-Hsien; Lee, Wen-Hsi; Current, Michael Ira; Samukawa, Seiji

2018-04-01

In this study, TiN/HfO2/Si metal-oxide-semiconductor (MOS) capacitors were etched by a neutral beam etching technique under two contrasting conditions. The configurations of neutral beam etching technique were specially designed to demonstrate a "damage-free" condition or to approximate "reactive-ion-etching-like" conditions to verify the effect of plasma-induced damage on electrical characteristics of MOS capacitors. The results show that by neutral beam etching (NBE), the interface state density (Dit) and the oxide trapped charge (Qot) were lower than routine plasma etching. Furthermore, the decrease in capacitor size does not lead to an increase in leakage current density, indicating less plasma induced side-wall damage. We present a plasma-induced gate stack damage model which we demonstrate by using these two different etching configurations. These results show that NBE is effective in preventing plasma-induced damage at the high-k/Si interface and on the high-k oxide sidewall and thus improve the electrical performance of the gate structure.

Strain-induced modulation of near-field radiative transfer.

PubMed

Ghanekar, Alok; Ricci, Matthew; Tian, Yanpei; Gregory, Otto; Zheng, Yi

2018-06-11

In this theoretical study, we present a near-field thermal modulator that exhibits change in radiative heat transfer when subjected to mechanical stress/strain. The device has two terminals at different temperatures separated by vacuum: one fixed and one stretchable. The stretchable side contains one-dimensional grating. When subjected to mechanical strain, the effective optical properties of the stretchable side are affected upon deformation of the grating. This results in modulation of surface waves across the interfaces influencing near-field radiative heat transfer. We show that for a separation of 100 nm, it is possible to achieve 25% change in radiative heat transfer for a strain of 10%.

The Effect of Reflexology on Chemotherapy-induced Nausea, Vomiting, and Fatigue in Breast Cancer Patients

PubMed Central

Özdelikara, Afitap; Tan, Mehtap

2017-01-01

Objective: Patients receiving chemotherapy struggle with the side effects of this treatment. These side effects obligate the patients to use not only the pharmacological methods but also non-pharmacological relaxing methods. This study was conducted to determine the effect of reflexology on chemotherapy-induced nausea, vomiting, and fatigue in breast cancer patients. Methods: The study was conducted as a pretest–posttest experimental design. The study was conducted with sixty patients, thirty as the control and thirty as the experimental groups. A sociodemographic form, Rhodes index of nausea, vomiting, and retching (INVR), and Brief Fatigue Inventory (BFI) were used to collect the data. Analysis of variance, t-test, percentage calculations, and Chi-square methods were used to evaluate the data. The data obtained were assessed using the “Statistical Package for Social Science 21.0” software. Results: It was determined that the difference between the total mean scores of INVR in the experimental and control groups was significant on the onset and first and second measurements, and the difference between total mean scores of development and distress between the groups was statistically significant in the third measurement (P < 0.05). The results of the study showed that the BFI mean scores of patients in the experimental group gradually decreased in the first, second, and third measurements (P < 0.05). Conclusions: The present study proved that reflexology decreased the experience, development, distress of nausea, vomiting, and retching as well as fatigue in the experimental group. Hence, the use of reflexology is recommended for chemotherapy-induced nausea, vomiting, and fatigue. PMID:28695171

Ketamine changes the local resting-state functional properties of anesthetized-monkey brain.

PubMed

Rao, Jia-Sheng; Liu, Zuxiang; Zhao, Can; Wei, Rui-Han; Zhao, Wen; Tian, Peng-Yu; Zhou, Xia; Yang, Zhao-Yang; Li, Xiao-Guang

2017-11-01

Ketamine is a well-known anesthetic. 'Recreational' use of ketamine common induces psychosis-like symptoms and cognitive impairments. The acute and chronic effects of ketamine on relevant brain circuits have been studied, but the effects of single-dose ketamine administration on the local resting-state functional properties of the brain remain unknown. In this study, we aimed to assess the effects of single-dose ketamine administration on the brain local intrinsic properties. We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to examine the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in the brain before and after ketamine injection. Paired comparisons were used to detect the significantly altered regions. Results showed that the fALFF of the prefrontal cortex (p=0.046), caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020) in post-injection stage significantly increased compared with those in pre-injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that of prefrontal cortex decreased (p<0.05). These findings demonstrated that single-dose ketamine administration can change the regional intensity and synchronism of brain activity, thereby providing evidence of ketamine-induced abnormal resting-state functional properties in primates. This evidence may help further elucidate the effects of ketamine on the cerebral resting status. Copyright © 2017. Published by Elsevier Inc.

Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double-Blind, Randomized Controlled Trial.

PubMed

Bertrand, Helene; Kyriazis, Marylene; Reeves, K Dean; Lyftogt, John; Rabago, David

2015-11-01

Capsaicin specifically activates, and then gradually exhausts, the transient receptor potential vanilloid type 1 (TRPV1) receptor, a key receptor in neuropathic pain. Activation of the TRPV-1 receptor is accompanied by burning pain. A natural substance or medication that can reduce the burning pain resulting from capsaicin application may have therapeutic potential in neuropathic pain. To assess the pain-relieving effects of a mannitol-containing cream in a capsaicin-based pain model. Randomized, placebo-controlled, double-blind clinical trial. Outpatient pain clinic. Twenty-five adults with pain-free lips. Capsaicin .075% cream was applied to both halves of each participant's upper lip, inducing pain via stimulation of the transient receptor potential vanilloid 1 (TRPV1, capsaicin) receptor, then removed after 5 minutes or when participants reported a burning pain of 8/10, whichever came first. A cream containing mannitol and the same cream without mannitol (control) were then immediately applied, 1 on each side of the lip, in an allocation-masked manner. Participants self-recorded a numeric rating scale (NRS, 0-10) pain score for each side of the lip per minute for 10 minutes. A t-test was performed to evaluate the pain score change from baseline between each side of the lip at each recording. Area under the curve (AUC) analysis was used to determine the overall difference between groups. Participants reached a capsaicin-induced pain level of 7.8 ± 1.0 points in 3.3 ± 1.6 minutes that was equal on both sides of the lip. Both groups reported progressive diminution of pain over the 10-minute study period. However, participants reported significantly reduced pain scores on the mannitol cream half-lip compared to control at 3 through 10 minutes (P < .05) and in AUC analysis (P < .001). Mannitol cream reduced self-reported pain scores in a capsaicin pain model more rapidly than a control cream, potentially via a TRPV1 receptor effect. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Hormonal Correlates of Clozapine-Induced Weight Gain in Psychotic Children: An Exploratory Study

ERIC Educational Resources Information Center

Sporn, Alexandra L.; Bobb, Aaron J.; Gogtay, Nitin; Stevens, Hanna; Greenstein, Deanna K.; Clasen, Liv S.; Tossell, Julia W.; Nugent, Thomas; Gochman, Peter A.; Sharp, Wendy S.; Mattai, Anand; Lenane, Marge C.; Yanovski, Jack A.; Rapoport, Judith L.

2005-01-01

Objective: Weight gain is a serious side effect of atypical antipsychotics, especially in childhood. In this study, the authors examined six weight gain-related hormones in patients with childhood-onset schizophrenia (COS) after 6 weeks of clozapine treatment. Method: Fasting serum samples for 24 patients with COS and 21 matched healthy controls…

TGF-.beta. antagonists as mitigators of radiation-induced tissue damage

DOEpatents

Barcellos-Hoff, Mary H.

1997-01-01

A method for treating tissue damage caused by radiation is described by use of a TGF-.beta. antagonist, such as an anti-TGF-.beta. antibody or a TGF-.beta. latency associated protein. It is administered not more than a week after exposure, and is particularly useful in mitigating the side effects of breast cancer therapy.

TGF-{beta} antagonists as mitigators of radiation-induced tissue damage

DOEpatents

Barcellos-Hoff, M.H.

1997-04-01

A method for treating tissue damage caused by radiation is described by use of a TGF-{beta} antagonist, such as an anti-TGF-{beta} antibody or a TGF-{beta} latency associated protein. It is administered not more than a week after exposure, and is particularly useful in mitigating the side effects of breast cancer therapy.

Effects of boundary-layer separation controllers on a desktop fume hood.

PubMed

Huang, Rong Fung; Chen, Jia-Kun; Hsu, Ching Min; Hung, Shuo-Fu

2016-10-02

A desktop fume hood installed with an innovative design of flow boundary-layer separation controllers on the leading edges of the side plates, work surface, and corners was developed and characterized for its flow and containment leakage characteristics. The geometric features of the developed desktop fume hood included a rearward offset suction slot, two side plates, two side-plate boundary-layer separation controllers on the leading edges of the side plates, a slanted surface on the leading edge of the work surface, and two small triangular plates on the upper left and right corners of the hood face. The flow characteristics were examined using the laser-assisted smoke flow visualization technique. The containment leakages were measured by the tracer gas (sulphur hexafluoride) detection method on the hood face plane with a mannequin installed in front of the hood. The results of flow visualization showed that the smoke dispersions induced by the boundary-layer separations on the leading edges of the side plates and work surface, as well as the three-dimensional complex flows on the upper-left and -right corners of the hood face, were effectively alleviated by the boundary-layer separation controllers. The results of the tracer gas detection method with a mannequin standing in front of the hood showed that the leakage levels were negligibly small (≤0.003 ppm) at low face velocities (≥0.19 m/s).

Cognitive behavioral therapy and physical exercise for climacteric symptoms in breast cancer patients experiencing treatment-induced menopause: design of a multicenter trial.

PubMed

Duijts, Saskia F A; Oldenburg, Hester S A; van Beurden, Marc; Aaronson, Neil K

2009-06-06

Premature menopause is a major concern of younger women undergoing adjuvant therapy for breast cancer. Hormone replacement therapy is contraindicated in women with a history of breast cancer. Non-hormonal medications show a range of bothersome side-effects. There is growing evidence that cognitive behavioral therapy (CBT) and physical exercise can have a positive impact on symptoms in naturally occurring menopause. The objective of this study is to investigate the efficacy of these interventions among women with breast cancer experiencing treatment-induced menopause. In a randomized, controlled, multicenter trial, we are evaluating the effectiveness of CBT/relaxation, of physical exercise and of these two program elements combined, in reducing menopausal symptoms, improving sexual functioning, reducing emotional distress, and in improving the health-related quality of life of younger breast cancer patients who experience treatment-induced menopause. 325 breast cancer patients (aged < 50) are being recruited from hospitals in the Amsterdam region, and randomly allocated to one of the three treatment groups or a 'waiting list' control group. Self-administered questionnaires are completed by the patients at baseline, and at 12 weeks (T1) and 6 months (T2) post-study entry. Upon completion of the study, women assigned to the control group will be given the choice of undergoing either the CBT or physical exercise program. Cognitive behavioral therapy and physical exercise are potentially useful treatments among women with breast cancer undergoing treatment-induced, premature menopause. For these patients, hormonal and non-hormonal therapies are contraindicated or have a range of bothersome side-effects. Hence, research into these interventions is needed, before dissemination and implementation in the current health care system can take place.

Alterations to Melanocortinergic, GABAergic and Cannabinoid Neurotransmission Associated with Olanzapine-Induced Weight Gain

PubMed Central

Weston-Green, Katrina; Huang, Xu-Feng; Deng, Chao

2012-01-01

Background/Aim Second generation antipsychotics (SGAs) are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapine-induced obesity. Methodology/Results Levels of pro-opiomelanocortin (POMC), neuropeptide Y (NPY) and glutamic acid decarboxylase (GAD65, enzyme for GABA synthesis) mRNA expression, and cannabinoid CB1 receptor (CB1R) binding density (using [3H]SR-141716A) were examined in the arcuate nucleus (Arc) and dorsal vagal complex (DVC) of female Sprague Dawley rats following 0.25, 0.5, 1.0 or 2.0 mg/kg olanzapine or vehicle (3×/day, 14-days). Consistent with its weight gain liability, olanzapine significantly decreased anorexigenic POMC and increased orexigenic NPY mRNA expression in a dose-sensitive manner in the Arc. GAD65 mRNA expression increased and CB1R binding density decreased in the Arc and DVC. Alterations to neurotransmission signals in the brain significantly correlated with body weight and adiposity. The minimum dosage threshold required to induce weight gain in the rat was 0.5 mg/kg olanzapine. Conclusions Olanzapine-induced weight gain is associated with reduced appetite-inhibiting POMC and increased NPY. This study also supports a role for the CB1R and GABA in the mechanisms underlying weight gain side-effects, possibly by altering POMC transmission. Metabolic dysfunction can be modelled in the female rat using low, clinically-comparable olanzapine doses when administered in-line with the half-life of the drug. PMID:22438946

Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-κB signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Juan; Xin, Beibei; Wang, Hui

Gastrin is absent in most normal adult pancreatic tissues but is highly expressed in pancreatic cancer tissues. Although Gastrin expression was reported to be associated with tumor proliferation in human pancreatic cancer, studies on the relationship between Gastrin and tumor metastasis in pancreatic cancer are rare. In this study, we performed an analysis to determine the effects of Gastrin on modulating the side populations, cell proportion and tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. We indicated that Gastrin and ABCG2 were widely expressed in pancreatic cancer cell lines and overexpressed in cancer tissues.more » Gastrin induced ABCG2 expression, and this effect was mediated by NF-κB activation. Gastrin regulated the SP proportion of BxPC-3 cells via modulating ABCG2 expression. Through the regulation of the functions of NF-κB/ABCG2, Gastrin functionally promoted the migration and invasion in pancreatic cancer cell. The present study indicated that Gastrin induced ABCG2 expression by activating NF-κB and thereby modulated the SP proportion, tumor cell metastatic potential and invasion activity in pancreatic cancer. Gastrin could serve as an effective therapeutic target for the metastasis of pancreatic cancer. - Highlights: • Gastrin induces ABCG2 expression mediated by NF-κB activation. • Gastrin regulates NF-κB's function that binds to the ABCG2 promoter in BxPC-3 cells. • Gastrin promotes the SP proportion in BxPC-3 cells by modulating ABCG2 expression via activation of NF-κB molecule. • Gastrin induces an increase in migration and invasion potential in pancreatic cancer cell by regulating NF-κB/ABCG2 signaling.« less

Methylphenidate-induced acute orofacial and extremity dyskinesia.

PubMed

Yilmaz, Ayse Esra; Donmez, Ahsen; Orun, Emel; Tas, Tugba; Isik, Bunyamin; Sonmez, Fatma Mujgan

2013-06-01

Methylphenidate is a short-acting stimulant. In this article, the authors report a 7-year-old male patient who presented with orofacial and limb dyskinesia after his first dose of methylphenidate treatment for a diagnosis of attention-deficit/hyperactivity disorder; he was also receiving sodium valproate treatment for epilepsy. Orofacial dyskinesia appeared 5 hours after methylphenidate administration, persisted for 10 hours, and had completely resolved within 2 days. Although limb dyskinesia after methylphenidate is a commonly reported side effect, to the authors' knowledge this is only the second reported case to develop both orofacial and limb dyskinesia in the acute period after the first dose of methylphenidate. This case is reported to emphasize the potential side effects of methylphenidate, individual differences in drug sensitivities, and drug-receptor interactions via different mechanisms.

Challenges Evaluating Chemotherapy-Induced Peripheral Neuropathy in Childhood Cancer Survivors.

PubMed

Mohrmann, Caroline; Armer, Jane; Hayashi, Robert J

Children treated for cancer are exposed to a variety of chemotherapeutic agents with known toxicity to the peripheral nervous system. The side effect of peripheral neuropathy can cause changes in sensation, function, and even cause pain. Although peripheral neuropathy is recognized by pediatric oncology nurses as an important and significant side effect, measuring neuropathy can be quite complex for clinical care and research efforts. With more children surviving a cancer diagnosis today, this issue is increasingly important for childhood cancer survivors. This article has reviewed existing literature examining peripheral neuropathy in childhood cancer survivors with particular interest paid to measurement tools available and needs for future research. It is important for nurses to choose appropriate measures for clinical care and research methods in order to have an impact on patients experiencing this condition.

Localization and delocalization of a one-dimensional system coupled with the environment

NASA Astrophysics Data System (ADS)

Zhu, Hong-Jun; Xiong, Shi-Jie

2010-03-01

We investigate several models of a one-dimensional chain coupling with surrounding atoms to elucidate disorder-induced delocalization in quantum wires, a peculiar behaviour against common wisdom. We show that the localization length is enhanced by disorder of side sites in the case of strong disorder, but in the case of weak disorder there is a plateau in this dependence. The above behaviour is the conjunct influence of the coupling to the surrounding atoms and the antiresonant effect. We also discuss different effects and their physical origin of different types of disorder in such systems. The numerical results show that coupling with the surrounding atoms can induce either the localization or delocalization effect depending on the values of parameters.

Competitive inhibition of the nondepolarizing muscle relaxant rocuronium on nicotinic acetylcholine receptor channels in the rat superior cervical ganglia.

PubMed

Zhang, Chengmi; Wang, Zhenmeng; Zhang, Jinmin; Qiu, Haibo; Sun, Yuming; Yang, Liqun; Wu, Feixiang; Zheng, Jijian; Yu, Weifeng

2014-05-01

A number of case reports now indicate that rocuronium can induce a number of serious side effects. We hypothesized that these side effects might be mediated by the inhibition of nicotinic acetylcholine receptors (nAChRs) at superior cervical ganglion (SCG) neurons. Conventional patch clamp recordings were used to study the effects of rocuronium on nAChR currents from enzymatically dissociated rat SCG neurons. We found that ACh induced a peak transient inward current in rat SCG neurons. Additionally, rocuronium suppressed the peak ACh-evoked currents in rat SCG neurons in a concentration-dependent and competitive manner, and it increased the extent of desensitization of nAChRs. The inhibitory rate of rocuronium on nAChR currents did not change significantly at membrane potentials between -70 and -20 mV, suggesting that this inhibition was voltage independent. Lastly, rocuronium preapplication enhanced its inhibitory effect, indicating that this drug might prefer to act on the closed state of nAChR channels. In conclusion, rocuronium, at clinically relevant concentrations, directly inhibits nAChRs at the SCG by interacting with both opened and closed states. This inhibition is competitive, dose dependent, and voltage independent. Blockade of synaptic transmission in the sympathetic ganglia by rocuronium might have potentially inhibitory effects on the cardiovascular system.

Long-term Nasal and Peri-oral Tightening by a Single Fractional Noninsulated Microneedle Radiofrequency Treatment

PubMed Central

2017-01-01

Background: The skin tightening effects induced by non-insulated microneedle radiofrequency have proved long-lasting. Our previous three-dimensional volumetric assessment showed significant facial tightening for up to six months. However, nasal and peri-oral tightening effects lasted longer. The objective of this study was to investigate the distribution of the long-term volumetric reduction in facial area induced by a single fractional non-insulated microneedle radiofrequency treatment. Methods: Fifteen Asian patients underwent full facial skin tightening using a sharply tapered non-insulated microneedle radiofrequency applicator with a novel fractionated pulse mode. Three-dimensional volumetric assessments were performed at six and 12 months post-treatment. Patients rated their satisfaction using a 5-point scale at each follow up. Results: Objective assessments with superimposed three-dimensional color images showed significant volumetric reduction in the nasal and peri-oral areas at 12 months post-treatment in all patients. Median volumetric reductions at six and 12 months post-treatment were 13.1 and 12.3ml, respectively. All of the patients were satisfied with their results 12 months post-treatment. Side effects were not observed. Conclusions: This single fractional NIMNRF treatment provided long-lasting nasal and peri-oral tightening as shown via 3D volumetric assessment. Moreover, NIMNRF produced minimal complications, downtime, and few side effects. This approach provides safe and effective treatment of skin tightening. PMID:28367261

Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer

PubMed Central

Pabla, Navjotsingh; Dong, Guie; Jiang, Man; Huang, Shuang; Kumar, M. Vijay; Messing, Robert O.; Dong, Zheng

2011-01-01

Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy. PMID:21633170

Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

PubMed

Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

2016-11-25

In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

Cardioprotective mechanisms of phytochemicals against doxorubicin-induced cardiotoxicity.

PubMed

Abushouk, Abdelrahman Ibrahim; Ismail, Ammar; Salem, Amr Muhammad Abdo; Afifi, Ahmed M; Abdel-Daim, Mohamed M

2017-06-01

Doxorubicin (DOX) is an anthracycline antibiotic, which is effectively used in the treatment of different malignancies, such as leukemias and lymphomas. Its most serious side effect is dose-dependent cardiotoxicity, which occurs through inducing oxidative stress apoptosis. Due to the myelosuppressive effect of dexrazoxane, a commonly-used drug to alleviate DOX-induced cardiotoxicity, researchers investigated the potential of phytochemicals for prophylaxis and treatment of this condition. Phytochemicals are plant chemicals that have protective or disease preventive properties. Preclinical trials have shown antioxidant properties for several plant extracts, such as those of Aerva lanata, Aronia melanocarpa, Astragalus polysaccharide, and Bombyx mori plants. Other plant extracts showed an ability to inhibit apoptosis, such as those of Astragalus polysaccharide, Azadirachta indica, Bombyx mori, and Allium stavium plants. Unlike synthetic agents, phytochemicals do not impair the clinical activity of DOX and they are particularly safe for long-term use. In this review, we summarized the results of preclinical trials that investigated the cardioprotective effects of phytochemicals against DOX-induced cardiotoxicity. Future human trials are required to translate these cardioprotective mechanisms into practical clinical implications. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The effect of inhaled K+ channel openers on bronchoconstriction and airway microvascular leakage in anaesthetised guinea pigs.

PubMed

Kidney, J C; Lotvall, J O; Lei, Y; Chung, K F; Barnes, P J

1996-01-18

Since orally administered K+ channel openers may have cardiovascular side effects, it is possible that inhaled administration would be preferred for the treatment of asthma. We have investigated whether inhaled levcromakalim and HOE 234 inhibit histamine-induced bronchoconstriction and airway plasma exudation in anaesthetised guinea pigs. We have also investigated whether inhaled HOE 234 inhibits the bronchoconstriction and plasma exudation induced by vagus nerve stimulation, which is due to the release of tachykinins from sensory nerves. Lung resistance was measured by airway resistance (RL) computed from airway and transpulmonary pressures and plasma exudation by measurement of Evans blue dye extravasation. Inhaled levcromakalim (25 mu g/ml) had a short duration of action, being effective against histamine-induced bronchoconstriction 2 min after pretreatment, but not at 10 min. Inhaled HOE 234 (25 mu g/ml) was similarly effective against histamine-induced bronchoconstriction but had a longer duration of action. Inhaled levcromakalim partially attenuated histamine-induced plasma extravasation in small airways, but not in the trachea or main bronchi, whereas inhaled HOE 234 had no effect. HOE 234 protected against non-adrenergic non-cholinergic nerve-induced bronchoconstriction, but had no effect on neurogenic- or substance P-induced plasma extravasation in the airway. Inhaled K+ channel openers protect against induced bronchoconstriction, but provide little or no protection against plasma exudation, possibly because of an increase in airway blood flow. In addition, inhaled HOE 234 had no effect on neurogenic leakage, suggesting that its vagal inhibitory effect on bronchoconstriction was on airway smooth muscle, rather than on release of neuropeptides from sensory nerves.

Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice

PubMed Central

Nishchal, B. S.; Rai, S.; Prabhu, M. N.; Ullal, Sheetal D.; Rajeswari, S.; Gopalakrishna, H. N.

2014-01-01

Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was induced in mice with haloperidol (1.0 mg/kg, intraperitoneally). The first group received the vehicle (10 ml/kg, orally), the second group received trihexyphenidyl (10 mg/kg, orally) and the remaining two groups received Tribulus terrestris (100, 200 mg/kg, orally). The animals were assessed after single and repeated dose administration for ten days, 30 min prior to haloperidol, using standard bar test. The result of the present study demonstrates Tribulus terrestris has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drug used for the same purpose. Our study indicates Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal side effects. PMID:25593394

Rutin-Enriched Extract from Coriandrum sativum L. Ameliorates Ionizing Radiation-Induced Hematopoietic Injury

PubMed Central

Han, Xiaodan; Xue, Xiaolei; Zhao, Yu; Li, Yuan; Liu, Weili; Zhang, Junling; Fan, Saijun

2017-01-01

Hematopoietic injury is a major cause of mortality in radiation accidents and a primary side effect in patients undergoing radiotherapy. Ionizing radiation (IR)-induced myelosuppression is largely attributed to the injury of hematopoietic stem and progenitor cells (HSPCs). Coriander is a culinary herb with multiple pharmacological effects and has been widely used in traditional medicine. In this study, flavonoids were identified as the main component of coriander extract with rutin being the leading compound (rutin-enriched coriander extract; RE-CE). We evaluated the radioprotective effect of RE-CE against IR-induced HSPCs injury. Results showed that RE-CE treatment markedly improved survival, ameliorated organ injuries and myelosuppression, elevated HSPCs frequency, and promoted differentiation and proliferation of HSPCs in irradiated mice. The protective role of RE-CE in hematopoietic injury is probably attributed to its anti-apoptotic and anti-DNA damage effect in irradiated HSPCs. Moreover, these changes were associated with reduced reactive oxygen species (ROS) and enhanced antioxidant enzymatic activities in irradiated HSPCs. Collectively, these findings demonstrate that RE-CE is able to ameliorate IR-induced hematopoietic injury partly by reducing IR-induced oxidative stress. PMID:28468251

The Effects of Electroacupuncture on Cyclophosphamide-Induced Emesis in Ferrets.

DTIC Science & Technology

1996-07-01

Other studies conducted by Dundee’s group showed that acupressure and transcutaneous electrical stimulation ( TENS ) of the same acupoints also benefited...typically left in place for 20-30 minutes. The effects of acupuncture may be augmented with electrical stimulation (EA) and/or heat (e.g. moxibustion). Side...electrodes (Grass) were attached to the end of the needles and electrical stimulation was applied (the EA parameters will be described in detail later

Effects of cyclosporin A on a kidney epithelial cell line (LLC-PK1).

PubMed

Becker, G M; Gandolfi, A J; Nagle, R B

1987-05-01

Cyclosporin A (CSA), a potent immunosuppressant with the adverse side effect of nephrotoxicity, inhibited cell growth of pig kidney tubule cells (LLC-PK1) in culture. CSA (10(-5) M) also induced intense cytoplasmic vacuolation and the formation of dense granules. At the same concentration an analogue of CSA, cyclosporin G, had much less effect. This cell line may prove useful for revealing the mechanism of CSA-nephrotoxicity and testing the nephrotoxic potential of new analogues of cyclosporine.

Melatonin protects chondrocytes from impairment induced by glucocorticoids via NAD+-dependent SIRT1.

PubMed

Yang, Wei; Kang, Xiaomin; Qin, Na; Li, Feng; Jin, Xinxin; Ma, Zhengmin; Qian, Zhuang; Wu, Shufang

2017-10-01

Intra-articular injection of glucocorticoids is used to relieve pain and inflammation in osteoarthritis patients, which is occasionally accompanied with the serious side effects of glucocorticoids in collagen-producing tissue. Melatonin is the major hormone released from the pineal gland and its beneficial effects on cartilage has been suggested. In the present study, we investigated the protective role of melatonin on matrix degeneration in chondrocytes induced by dexamethasone (Dex). The chondrocytes isolated from mice knee joint were treated with Dex, melatonin, EX527 and siRNA targeted for SIRT6, respectively. Dex treatment induced the loss of the extracellular matrix, NAD + /NADH ratio and NADPH concentration in chondrocytes. Melatonin alone have no effect on the quantity of proteoglycans and collagen type IIa1, however, the pretreatment of melatonin reversed the negative effects induced by Dex. Meanwhile, the significant decrease in NAD + /NADH ratio and NADPH concentration in Dex group were up-regulated by pretreatment of melatonin. Furthermore, it was revealed that inhibition of SIRT1 blocked the protective effects of melatonin. The enhancement of NAD + -dependent SIRT1 activity contributes to the chondroprotecfive effects of melatonin, which has a great benefit to prevent dexamethasone-induced chondrocytes impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

Randomized controlled trial of the cognitive side-effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS).

PubMed

Moscrip, Tammy D; Terrace, Herbert S; Sackeim, Harold A; Lisanby, Sarah H

2006-02-01

Magnetic seizure therapy (MST) is under development as a means of improving the cognitive side-effect profile of electroconvulsive therapy (ECT) by inducing more spatially delimited seizures that spare cortical regions involved in memory. We tested whether MST had a cognitive side-effect profile distinct from electroconvulsive shock (ECS) in a non-human primate model, using the Columbia University Primate Cognitive Profile, which has been shown to be sensitive to the cognitive effects of ECS. Using a within-subject cross-over design, daily ECS, MST, and sham (anaesthesia-only) interventions were administered in 5-wk blocks. Rhesus macaques (n = 2) were trained on a long-term memory task, an anterograde learning and memory task, and a combined anterograde and retrograde task where learning and memory were evaluated for new and previously learned 3-item lists. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-h retention interval. Overall, monkeys were least accurate following ECS (p's < 0.05) compared to sham and MST. This effect was most marked for long-term memory of a constant target, short-term memory of a variable target and recall of previously learned 3-item lists. Monkeys were slowest to complete all tasks following ECS (p's = 0.0001). Time to task completion following MST did not differ from sham. These findings suggest that MST results in a more benign acute cognitive side-effect profile than ECS in this model, consistent with initial observations with human MST.

The Price of Tumor Control: An Analysis of Rare Side Effects of Anti-CTLA-4 Therapy in Metastatic Melanoma from the Ipilimumab Network

PubMed Central

Voskens, Caroline J.; Goldinger, Simone M.; Loquai, Carmen; Robert, Caroline; Kaehler, Katharina C.; Berking, Carola; Bergmann, Tanja; Bockmeyer, Clemens L.; Eigentler, Thomas; Fluck, Michael; Garbe, Claus; Gutzmer, Ralf; Grabbe, Stephan; Hauschild, Axel; Hein, Rüdiger; Hundorfean, Gheorghe; Justich, Armin; Keller, Ullrich; Klein, Christina; Mateus, Christine; Mohr, Peter; Paetzold, Sylvie; Satzger, Imke; Schadendorf, Dirk; Schlaeppi, Marc; Schuler, Gerold; Schuler-Thurner, Beatrice; Trefzer, Uwe; Ulrich, Jens; Vaubel, Julia; von Moos, Roger; Weder, Patrik; Wilhelm, Tabea; Göppner, Daniela; Dummer, Reinhard; Heinzerling, Lucie M.

2013-01-01

Background Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects. PMID:23341990

Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP) and CCL11/eotaxin-1 in human asthmatic airways.

PubMed

Nino, Gustavo; Huseni, Shehlanoor; Perez, Geovanny F; Pancham, Krishna; Mubeen, Humaira; Abbasi, Aleeza; Wang, Justin; Eng, Stephen; Colberg-Poley, Anamaris M; Pillai, Dinesh K; Rose, Mary C

2014-01-01

Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. Primary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC) from normal (n = 3) and asthmatic (n = 3) donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20) vs. non-asthmatic uninfected controls (n = 20). Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. Our data demonstrate that: 1) Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2) TSLP exposure induces unidirectional (apical) secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3) Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

Directional Secretory Response of Double Stranded RNA-Induced Thymic Stromal Lymphopoetin (TSLP) and CCL11/Eotaxin-1 in Human Asthmatic Airways

PubMed Central

Perez, Geovanny F.; Pancham, Krishna; Mubeen, Humaira; Abbasi, Aleeza; Wang, Justin; Eng, Stephen; Colberg-Poley, Anamaris M.; Pillai, Dinesh K.; Rose, Mary C.

2014-01-01

Background Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. Methods Primary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC) from normal (n = 3) and asthmatic (n = 3) donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20) vs. non-asthmatic uninfected controls (n = 20). Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. Results Our data demonstrate that: 1) Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2) TSLP exposure induces unidirectional (apical) secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3) Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. Conclusions There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations. PMID:25546419

Network pharmacology-based identification of protective mechanism of Panax Notoginseng Saponins on aspirin induced gastrointestinal injury.

PubMed

Zhu, Baochen; Zhang, Wantong; Lu, Yang; Hu, Shaonan; Gao, Rui; Sun, Zongxi; Chen, Xiaonan; Ma, Junming; Guo, Shuang; Du, Shouying; Li, Pengyue

2018-05-29

Aspirin is the first line therapy for cardiovascular and cerebrovascular diseases and is widely used. However aspirin-induced gastrointestinal injury is one of its most common side effect which limits long-term use. Panax Notoginseng Saponins(PNS) which is also used to prevent thrombus may alleviate this side effect according to previous clinical evidences. Owing to the complexity of drug combination, the protective mechanism of PNS on aspirin-induced gastrointestinal injury remains unclear. Therefore, a network pharmacology-based strategy was proposed in this study to address this problem. A network pharmacology approach comprising multiple components, candidate targets of each component, known therapeutic targets, network analysis has been used in this study. Also, we establish aspirin-induced gastrointestinal injury model by the oral administration of aspirin (0.5 g/kg body weight) to verify the predicted targets from network pharmacology. All rats was randomly allocated to control groups (n = 6),aspirin groups (n = 6)and aspirin + PNS groups (n = 6) and conducted H&E staining and ELISA for VEGFA. The comprehensive systematic approach was successfully to identify 5 compounds and 154 candidate targets in PNS and 479 candidate targets in aspirin. After network establishment and analysis, 27 potential targets hit by PNS, aspirin and 6 kind of gastrointestinal diseases were found. The experiments results indicated that aspirin group has visible inflammation and lesions while aspirin + PNS group have not. The higher expression of VEGFA in aspirin + PNS group verified the predicted potential protective targets of PNS. PNS may have protective function for aspirin-induced gastrointestinal injury through increasing VEGFA expression. Network pharmacology strategy may provide a forceful tool for exploring the mechanism of herb medicine and discovering novel bioactive ingredients. Copyright © 2018. Published by Elsevier Masson SAS.

A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss

PubMed Central

Lozano, Alysia; Wright, Courtney; Vardanyan, Anna; King, Tamara; Largent-Milnes, Tally M.; Nelson, Mark; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W; Vanderah, Todd W.

2010-01-01

Aims Cannabinoid CB2 agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB2 agonist, does not demonstrate central nervous system side-effects seen with CB1 agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB2 selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB2 agonist administered over a 7 day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation. Main Methods A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur. Key Findings Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7 days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures. Significance These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain. PMID:20176037

Effects of rocuronium pretreatment on muscle enzyme levels following succinylcholine.

PubMed

Farhat, Kulsoom; Waheed, Akbar; Pasha, Anwar Kamal; Tariq, Muhammad

2013-09-01

Succinylcholine revolutionized anaesthetic practice by providing intense neuromuscular blockade of very rapid onset and ultrashort duration, thereby greatly easing the maneuver of tracheal intubation. However the worth of succinylcholine is limited by the frequent occurrence of muscular side effects which manifest biochemically in the form of rise in serum creatine kinase (CK). The administration of small doses of nondepolarizing muscle relaxants before the administration of succinylcholine has been shown to decrease the incidence and severity of muscular side effects experienced by the patients. This study was aimed at evaluating the efficacy of technique in reducing the muscular side effects of succinylcholine, biochemically manifested as rise in CK. Sixty healthy adults were enrolled in the study who were scheduled for minor muscle cutting surgeries under general anaesthesia. They were assigned at random to two groups of thirty patients each. They randomly received succinylcholine for intubation and a precurarization dose of rocuronium followed by succinylcholine for intubation. Blood samples were drawn for estimation of serum creatinine kinase. There was a significantly raised CK in the succinylcholine group. In the precurarization group the rise in CK was prevented and the levels were significantly less as compared to the group which received succinylcholine alone. Present study concluded that precurarization with rocuronium was effective in reducing the succinylcholine-induced rise in creatinine kinase.

Continuous extraovular administration of prostaglandin F2alpha for midtrimester abortion.

PubMed

Lauersen, N H; Wilson, K H

1974-09-15

Midtrimester abortion was successfully induced in 74 of 76 patients by a continuous extraovular administration of (PGF2alpha) prostaglandin F2alpha via a constant-infusion pump. 2 patients in the 13th-14th weeks of gestation failed to abort despite good uterine activity. The mean abortion time for successful inductions was 16.21 hours. Parous patients aborted somewhat faster than nulliparous patients, but the difference was not statistically significant. All patients were monitored throughout the abortion procedure, and uterine activity was calculated and analyzed. Uterine activity developed within 15 minutes of PGF2alpha instillation and showed the characteristic uterine response to PGs with a sharp rise in intrauterine tonus. The gastrointestinal side effects in this series were much less than those reported for intraamniotic instillation of PG, and there was good patient tolerance of the procedure. The main complication of extraovular administration of PGF2alpha for midtrimester abortion was endometritis, which occurred in 7 patients. The patients who developed endometritis had, as a group, longer abortion times (mean=28 hours). 3 patients with severe preeclampsia and intrauterine death in the third trimester also had successfully induced labor with extraovular administration of PGF2alpha. The method of PGF2alpha administration in the series was found to have a high success rate, good patient tolerance, and fewer side effects than when abortion was induced by intraamniotic instillation of PGF2alpha.