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Sample records for oral long-acting muscle

  1. Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study.

    PubMed

    Buckley, Peter F; Schooler, Nina R; Goff, Donald C; Hsiao, John; Kopelowicz, Alexander; Lauriello, John; Manschreck, Theo; Mendelowitz, Alan J; Miller, Del D; Severe, Joanne B; Wilson, Daniel R; Ames, Donna; Bustillo, Juan; Mintz, Jim; Kane, John M

    2015-03-01

    Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician's choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials. PMID:24870446

  2. Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany.

    PubMed

    Laux, Gerd; Heeg, Bart; van Hout, Ben A; Mehnert, Angelika

    2005-01-01

    Schizophrenia is one of the most expensive psychiatric conditions because of high direct and indirect costs associated with the nature of the illness, its resistance to treatment and the consequences of relapse. Long-acting risperidone is a new formulation of an atypical antipsychotic drug that also offers the improvements in compliance associated with haloperidol depot. The aim of this simulation study was to compare the benefits and costs of three pharmacological treatment strategies comprising first-line treatment with long-acting risperidone injection, a haloperidol depot or an oral atypical antipsychotic agent, over a 5-year period in Germany. A discrete event simulation model was developed to compare three treatment scenarios from the perspective of major third-party payers (sickness funds and social security 'Sozialversicherung'). The scenarios comprised first-line treatment with haloperidol depot (scenario 1), long-acting risperidone (scenario 2) and oral olanzapine (scenario 3). Switches to second or third-line options were allowed when side-effects occurred or a patient suffered more than a fixed number of relapses. The model accounted for fixed patient characteristics, and on the basis of these, simulated patient histories according to several time-dependent variables. The time horizon for this model was limited to 5 years, and in accordance with German guidelines, costs and effects were discounted by between 3 and 10%. Direct costs included medication, type of physician visits and treatment location. Indirect costs were not included. Information on treatment alternatives, transition probabilities, model structure and healthcare utilization were derived from the literature and an expert panel. Outcomes were expressed in terms of the number and duration of psychotic episodes, cumulative symptom scores, costs, and quality-adjusted life-years (QALY). Univariate sensitivity analyses were carried out, as were subgroup analyses based on disease severity and

  3. Improvement in cardiac performance by oral long-acting theophylline in chronic obstructive pulmonary disease.

    PubMed

    Matthay, R A; Berger, H J; Davies, R; Loke, J; Gottschalk, A; Zaret, B L

    1982-11-01

    Although oral theophylline is a widely used bronchodilator in chronic obstructive pulmonary disease (COPD), its effects upon cardiac performance have not been fully established. The effect of slow release oral theophylline upon right ventricular and left ventricular ejection fraction was evaluated using first-pass quantitative radionuclide angiocardiography in 15 patients with COPD. After 72 hours of therapy, oral theophylline significantly increased right ventricular ejection fraction (42% to 48%, p less than 0.005). In 7 of 10 patients with depressed baseline right ventricular performance, including two with cor pulmonale, right ventricular ejection fraction normalized (greater than or equal to 45%). After long-term therapy, an average of 16 weeks, right ventricular fraction also increased (43% to 48%, p less than 0.005). Left ventricular ejection fraction improved significantly from 64% to 68% (p less than 0.05) at 72 hours and from 61% to 65% (p less than 0.025) after long-term therapy. These data indicate that oral theophylline produces a sustained modest enhancement of resting biventricular performance in COPD.

  4. Comparative pharmacokinetics of a new oral long-acting formulation of doxycycline hyclate: A canine clinical trial.

    PubMed

    Arciniegas Ruiz, Sara Melisa; Gutiérrez Olvera, Lilia; Bernad Bernad, María Josefa; Caballero Chacón, Sara Del Carmen; Vargas Estrada, Dinorah

    2015-12-01

    Doxycicline is used in dogs as treatment of several bacterial infections, mycoplasma, chlamydia and rickettsial diseases. However, it requires long treatments and several doses to be effective. The aim of this study was to determine the pharmacokinetics of four formulations of doxycycline hyclate, administered orally, with different proportions of excipients, acrylic acid-polymethacrylate-based matrices, to obtain longer therapeutic levels than conventional formulation. Forty-eight dogs were randomly assigned in five groups to receive a single oral dose (20mg/kg) of doxycycline hyclate without excipients (control) or a long-acting formulation containing doxycycline, acrylic acid polymer, and polymethacrylate in one of the following four proportions: DOX1(1:0.25:0.0035), DOX2(1:0.5:0.0075), DOX3 (1:1:0.015), or DOX4(1:2:0.0225). Temporal profiles of serum concentrations were obtained at several intervals after each treatment. Therapeutic concentrations were observed for 60h for DOX1 and DOX4, 48h for DOX2 and DOX3 and only 24h for DOX-C. None of the pharmacokinetic parameter differed significantly between DOX1 and DOX2 or between DOX3 and DOX4; however, the findings for the control treatment were significantly different compared to all four long-acting formulations. Results indicated that DOX1 had the most adequate pharmacokinetic-pharmacodynamic relationships for a time-dependent drug and had longer release times than did doxycycline alone. However, all four formulations can be effective depend on the minimum effective serum doxycycline concentration of the microorganism being treated. These results suggest that the use of any of these formulations can reduce the frequency of administration, the patient's stress, occurrence of adverse effects and the cost of treatment.

  5. CTEP: a novel, potent, long-acting, and orally bioavailable metabotropic glutamate receptor 5 inhibitor.

    PubMed

    Lindemann, Lothar; Jaeschke, Georg; Michalon, Aubin; Vieira, Eric; Honer, Michael; Spooren, Will; Porter, Richard; Hartung, Thomas; Kolczewski, Sabine; Büttelmann, Bernd; Flament, Christophe; Diener, Catherine; Fischer, Christophe; Gatti, Silvia; Prinssen, Eric P; Parrott, Neil; Hoffmann, Gerhard; Wettstein, Joseph G

    2011-11-01

    The metabotropic glutamate receptor 5 (mGlu5) is a glutamate-activated class C G protein-coupled receptor widely expressed in the central nervous system and clinically investigated as a drug target for a range of indications, including depression, Parkinson's disease, and fragile X syndrome. Here, we present the novel potent, selective, and orally bioavailable mGlu5 negative allosteric modulator with inverse agonist properties 2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP). CTEP binds mGlu5 with low nanomolar affinity and shows >1000-fold selectivity when tested against 103 targets, including all known mGlu receptors. CTEP penetrates the brain with a brain/plasma ratio of 2.6 and displaces the tracer [(3)H]3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-methyl-oxime (ABP688) in vivo in mice from brain regions expressing mGlu5 with an average ED(50) equivalent to a drug concentration of 77.5 ng/g in brain tissue. This novel mGlu5 inhibitor is active in the stress-induced hyperthermia procedure in mice and the Vogel conflict drinking test in rats with minimal effective doses of 0.1 and 0.3 mg/kg, respectively, reflecting a 30- to 100-fold higher in vivo potency compared with 2-methyl-6-(phenylethynyl)pyridine (MPEP) and fenobam. CTEP is the first reported mGlu5 inhibitor with both long half-life of approximately 18 h and high oral bioavailability allowing chronic treatment with continuous receptor blockade with one dose every 48 h in adult and newborn animals. By enabling long-term treatment through a wide age range, CTEP allows the exploration of the full therapeutic potential of mGlu5 inhibitors for indications requiring chronic receptor inhibition. PMID:21849627

  6. A Prospective Study Comparing the Long-term Effectiveness of Injectable Risperidone Long-acting Therapy and Oral Aripiprazole in Patients with Schizophrenia

    PubMed Central

    Macfadden, Wayne; Ma, Yi-Wen; Thomas Haskins, J.; Bossie, Cynthia A.

    2010-01-01

    Objective: To test the hypothesis that long-term maintenance with injectable risperidone long-acting therapy is superior to oral daily aripiprazole in stable patients with schizophrenia. Design: This two-year, rater-blinded, open-label, multicenter study (NCT00299702) randomized subjects to injectable risperidone long-acting therapy (25–50mg, injected every 2 weeks) or oral aripiprazole (5–30mg/day), with study visits every two weeks. Subjects who met relapse criteria or discontinued study drug could remain in the study. Setting: Clinical trial. Participants: Stable subjects with schizophrenia not adequately benefiting from current treatment who experienced two or more relapses in the past two years. If recently relapsed, subjects were stabilized (per clinician judgment) for two or more months before entry. Measurements: Primary endpoints: time to relapse and time in remission. Safety assessments included adverse event reporting. Results: Of 355 subjects randomized, 349 were in the intent-to-treat analysis set. Data inspection revealed that 53 (14.9%) randomized subjects deviated from inclusion/exclusion criteria, most commonly not meeting stability requirements. At baseline, mean (standard deviation [SD]) Positive and Negative Syndrome Scale total score was 68.9 (14.6); 115 (33.0%) intent-to-treat subjects met remission criteria. Approximately 29 percent in each group discontinued the study before completing two years. No significant between-group differences were noted in time to relapse or time in remission. No new tolerability issues were identified. Conclusion: Results failed to demonstrate superiority with injectable risperidone long-acting therapy versus oral aripiprazole. The study design did not allow for valid conclusions of equivalence or noninferiority. Although this study attempted to mimic a real-world treatment setting for stable patients, the broad study population, the lack of patient selection for nonadherence, biweekly visits, regular

  7. Optimization of isoxazoline amide benzoxaboroles for identification of a development candidate as an oral long acting animal ectoparasiticide.

    PubMed

    Zhang, Yong-Kang; Plattner, Jacob J; Easom, Eric E; Akama, Tsutomu; Zhou, Yasheen; White, W Hunter; Defauw, Jean M; Winkle, Joseph R; Balko, Terry W; Cao, Jianxin; Ge, Zhixin; Yang, Jianzhang

    2016-07-01

    Novel isoxazoline amide benzoxaboroles were designed and synthesized to optimize the ectoparasiticide activity of this chemistry series against ticks and fleas. The study identified an orally bioavailable molecule, (S)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide (23), with a favorable pharmacodynamics profile in dogs (Cmax=7.42ng/mL; Tmax=26.0h; terminal half-life t1/2=127h). Compound 23, a development candidate, demonstrated 100% therapeutic effectiveness within 24h of treatment, with residual efficacy of 97% against American dog ticks (Dermacentor variabilis) on day 30 and 98% against cat fleas (Ctenocephalides felis) on day 32 after a single oral dose at 25mg/kg in dogs.

  8. The Comparative Effectiveness of Long-Acting Injectable vs. Oral Antipsychotic Medications in the Prevention of Relapse: A Case Study in CER in Psychiatry

    PubMed Central

    Kane, John M.; Kishimoto, Taishiro; Correll, Christoph U.

    2013-01-01

    Objective As psychopathology and social functioning can worsen with repeated psychotic episodes in schizophrenia, relapse prevention is critical. Because high non-adherence rates limit the efficacy of pharmacotherapy, the use of long-acting injectable antipsychotics (LAIs) is considered an important treatment option. To date, many studies comparing LAIs and oral antipsychotics have been conducted; however, the results are mixed, and careful interpretation of the data is required. Study Design Selective review of existing literature regarding LAIs. We especially focused the discussion on the impact of the design of studies with different approaches comparing LAIs and oral antipsychotics in preventing relapse. Result The results were diverse and were influenced by the design utilized, i.e., randomized controlled trials (RCTs) showed LAIs and oral antipsychotics to have similar effects, whereas mirror-image and some large cohort studies showed LAIs to be superior to oral antipsychotics. Conclusion Divergent results from studies using different methodologies creates a dilemma for comparative effectiveness research, and LAI studies may serve as an example of a situation where a conventional RCT is not the gold standard. Traditional RCTs generally increase adherence compared to clinical practice and, therefore, might not be well suited to detect differences between LAIs and oral medications, because any increase in adherence effects patients on oral medications more than those on LAIs and thus leads to an underestimation of any potential difference in effectiveness. A possible solution would be the implementation of a true effectiveness trial,. in which post-randomization involvement would be kept to a minimum to better reflect routine practice. PMID:23849151

  9. Comparison of olanzapine long-acting injection and oral olanzapine: a 2-year, randomized, open-label study in outpatients with schizophrenia.

    PubMed

    Detke, Holland C; Weiden, Peter J; Llorca, Pierre-Michel; Choukour, Moutaz; Watson, Susan B; Brunner, Elizabeth; Ascher-Svanum, Haya

    2014-08-01

    We compared long-term treatment effectiveness of monthly olanzapine long-acting injection (LAI) with that of oral olanzapine. Outpatients with 2 or more episodes of psychotic worsening in the past 24 months with Positive and Negative Syndrome Scale total score of lower than 70 were randomized to 405 mg/4 weeks of olanzapine LAI (n = 264) or 10 mg/d of oral olanzapine (n = 260) for 2 years of open-label treatment. Dosing thereafter was flexible (150-405 mg/4 weeks of LAI vs 5-20 mg/d of oral). Primary outcome was time to all-cause discontinuation. At baseline, patients were clinically stable (mean Positive and Negative Syndrome Scale total score of 57). Seventeen percent of patients had been psychiatrically hospitalized in the previous 6 months, and 4.6% were rated nonadherent in the month before study entry. The groups did not differ significantly in median time to all-cause discontinuation (645 days for LAI, 678 days for oral; P = 0.61), discontinuation rate (53.8% for LAI, 51.2% for oral; P = 0.60), or relapse rate (20.1% for LAI, 18.5% for oral; P = 0.66). Postbaseline psychiatric hospitalization rate was low for both groups (7.6% for LAI, 9.2% for oral), but mean hospitalization duration was significantly longer for oral patients (1.80 days [20 for those hospitalized] vs 0.43 days [6 for those hospitalized], P = 0.02). There were no clinically significant group differences in adverse events or safety measures. No post-injection delirium/sedation syndrome events occurred. In conclusion, olanzapine LAI and oral olanzapine were similarly effective and well tolerated for up to 2 years of treatment in patients with schizophrenia. Treatment discontinuation for olanzapine LAI was similar to that of oral olanzapine, despite the 3-hour post-injection observation period and other precautionary procedures related to risk of post-injection delirium/sedation syndrome. PMID:24781441

  10. Reversible competitive α-ketoheterocycle inhibitors of fatty acid amide hydrolase containing additional conformational constraints in the acyl side chain: orally active, long-acting analgesics.

    PubMed

    Ezzili, Cyrine; Mileni, Mauro; McGlinchey, Nicholas; Long, Jonathan Z; Kinsey, Steven G; Hochstatter, Dustin G; Stevens, Raymond C; Lichtman, Aron H; Cravatt, Benjamin F; Bilsky, Edward J; Boger, Dale L

    2011-04-28

    A series of α-ketooxazoles containing conformational constraints in the C2 acyl side chain of 2 (OL-135) were examined as inhibitors of fatty acid amide hydrolase (FAAH). Only one of the two possible enantiomers displayed potent FAAH inhibition (S vs R enantiomer), and their potency is comparable or improved relative to 2, indicating that the conformational restriction in the C2 acyl side chain is achievable. A cocrystal X-ray structure of the α-ketoheterocycle 12 bound to a humanized variant of rat FAAH revealed its binding details, confirmed that the (S)-enantiomer is the bound active inhibitor, shed light on the origin of the enantiomeric selectivity, and confirmed that the catalytic Ser241 is covalently bound to the electrophilic carbonyl as a deprotonated hemiketal. Preliminary in vivo characterization of the inhibitors 12 and 14 is reported demonstrating that they raise brain anandamide levels following either intraperitoneal (ip) or oral (po) administration indicative of effective in vivo FAAH inhibition. Significantly, the oral administration of 12 caused dramatic accumulation of anandamide in the brain, with peak levels achieved between 1.5 and 3 h, and these elevations were maintained over 9 h. Additional studies of these two representative members of the series (12 and 14) in models of thermal hyperalgesia and neuropathic pain are reported, including the demonstration that 12 administered orally significantly attenuated mechanical (>6 h) and cold (>9 h) allodynia for sustained periods consistent with its long-acting effects in raising the endogenous concentration of anandamide.

  11. Effectiveness of long-acting injectable risperidone versus oral antipsychotics in the treatment of recent-onset schizophrenia: a case-control study.

    PubMed

    Barrio, Pablo; Batalla, Albert; Castellví, Pere; Hidalgo, Diego; García, Marta; Ortiz, Ana; Grande, Iria; Pons, Alexandre; Parellada, Eduard

    2013-07-01

    Long-acting injectable antipsychotics may offer a relevant improvement in treatment adherence in recent-onset psychosis, leading to a decreased rate of hospital readmission, a better rate of clinical remission and improved psychosocial adjustment. The aim of the study was to compare the clinical remission rates, number of hospital readmissions and personal and social functioning after 2 years between patients with recent-onset schizophrenia (<2 years) in treatment with risperidone long-acting injectable (RLAI) and patients with recent-onset schizophrenia receiving oral antipsychotics. This is a case-control study comparing patients with recent-onset schizophrenia who initiated RLAI treatment between 2004 and 2008 (n=26) with a control group matched for age and sex, diagnosed with recent-onset schizophrenia and treated with oral antipsychotics (n=26). Study assessments included sociodemographic variables, the Positive and Negative Syndrome Scale, the Personal and Social Functioning Scale, the number of hospital readmissions and the Andreasen remission criteria. To assess the effect of treatment on each dependent variable, separate generalized estimating equations models were constructed. After 2 years of treatment, and adjusting for educational level, the RLAI group showed a greater reduction in the Positive and Negative Syndrome Scale total scale [mean (SD)=47.7 (12.0) vs. 66.2 (18.5); mean difference =-17.56; 95% confidence interval (CI)=-27.11 to -8.00; P<0.001], as well as in the negative [mean (SD) 14.3 (6.1) vs. 19.4 (6.4); mean difference=-5.02; 95% CI=-8.28 to -1.77; P=0.002] and general psychopathology [mean (SD)=23.4 (6.3) vs. 32.7 (8.1); mean difference=-9.16; 95% CI=-13.3 to -5.03; P<0.001] subscales compared with the oral antipsychotic group. Personal and Social Functioning Scale scores were also higher in the RLAI group [mean (SD)=72.4 (14.8) vs. 59.7 (13.5); mean difference=13.41; 95% CI=5.65-21.18; P<0.001]. Although not statistically significant

  12. An Exploratory, Open-Label, Randomized Trial Comparing Risperidone Long-Acting Injectable with Oral Antipsychotic Medication in the Treatment of Early Psychosis.

    PubMed

    Malla, Ashok; Chue, Pierre; Jordan, Gerald; Stip, Emmanuel; Koczerginski, David; Milliken, Heather; Joseph, Anil; Williams, Richard; Adams, Beverly; Manchanda, Rahul; Oyewumi, Kola; Roy, Marc-André

    2016-01-01

    Few studies have examined effectiveness and tolerability of risperidone long-acting injections (RLAI) in the early phase of a schizophrenia spectrum (SS) disorder using a randomized controlled trial (RCT) design. Eighty-five patients in early phase of an SS disorder were randomized to receive either oral second-generation antipsychotics (SGAs; n=41) or RLAI (n=44) over two years. Analyses were conducted on eligible participants (n=77) for the stabilization (maximum 18 weeks) and maintenance phases (up to Week 104) on primary outcome measures of time to stabilization and relapse, change in symptoms and safety, and comparisons made across the two groups. Both groups showed improvement on Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression-Severity (CGI-S) scores. There were no time X group interactions on any of the primary outcome measures. Post hoc examination revealed that the RLAI group showed greater change on CGI-S and PANSS negative symptom scores during the stabilization phase, while the oral group reached the same level of improvement during the maintenance phase. The current exploratory study suggests that-within an RCT design-RLAI and oral SGAs are equally effective and have similar safety profiles in patients in the early phase of SS disorders. Thus, RLAI offers no advantage to patients in early phase of SS disorders, but is likely to be effective and safe for those who may have problems with adherence and may either choose to take it or be prescribed under conditions of external control such as community treatment orders.

  13. Effect of formoterol, a long-acting β2-adrenergic agonist, on muscle strength and power output, metabolism, and fatigue during maximal sprinting in men.

    PubMed

    Kalsen, Anders; Hostrup, Morten; Backer, Vibeke; Bangsbo, Jens

    2016-06-01

    The aim was to investigate the effect of the long-acting β2-adrenergic agonist formoterol on muscle strength and power output, muscle metabolism, and phosphorylation of CaMKII Thr(287) and FXYD1 during maximal sprinting. In a double-blind crossover study, 13 males [V̇o2 max: 45.0 ± 0.2 (means ± SE) ml·min(-1)·kg(-1)] performed a 30-s cycle ergometer sprint after inhalation of either 54 μg of formoterol (FOR) or placebo (PLA). Before and after the sprint, muscle biopsies were collected from vastus lateralis and maximal voluntary contraction (MVC), and contractile properties of quadriceps were measured. Oxygen uptake was measured during the sprint. During the sprint, peak power, mean power, and end power were 4.6 ± 0.8, 3.9 ± 1.1, and 9.5 ± 3.2% higher (P < 0.05) in FOR than in PLA, respectively. Net rates of glycogenolysis and glycolysis were 45.7 ± 21.0 and 28.5 ± 13.4% higher (P < 0.05) in FOR than in PLA, respectively, and the decrease in ATP content was lower (P < 0.05) in FOR than in PLA (3.7 ± 1.5 vs. 8.0 ± 1.6 mmol/kg dry weight). There was no difference in breakdown of phosphocreatine and oxygen uptake between treatments. Before and after the sprint, MVC and peak twitch force were higher (P < 0.05) in FOR than in PLA. No differences were observed in phosphorylation of CaMKII Thr(287) and FXYD1 between treatments before the sprint, whereas phosphorylation of CaMKII Thr(287) and FXYD1 was greater (P < 0.05) in FOR than in PLA after the sprint. In conclusion, formoterol-induced enhancement in power output during maximal sprinting is associated with increased rates of glycogenolysis and glycolysis that may counteract development of fatigue.

  14. Long-acting muscarinic antagonists.

    PubMed

    Melani, Andrea S

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of death and disability worldwide. Inhaled bronchodilators are the mainstay of COPD pharmacological treatment. Long-acting muscarinic antagonists (LAMAs) are a major class of inhaled bronchodilators. Some LAMA/device systems with different characteristics and dosing schedules are currently approved for maintenance therapy of COPD and a range of other products are being developed. They improve lung function and patient-reported outcomes and reduce acute bronchial exacerbations with good safety. LAMAs are used either alone or associated with long-acting β₂-agonists, eventually in fixed dose combinations. Long-acting β₂-agonist/LAMA combinations assure additional benefits over the individual components alone. The reader will obtain a view of the safety and efficacy of the different LAMA/device systems in COPD patients. PMID:26109098

  15. Long-acting hormonal contraception.

    PubMed

    Benagiano, Giuseppe; Gabelnick, Henry; Brosens, Ivo

    2015-11-01

    Today, a new category of fertility-regulating agents has been created: long-acting, reversible hormonal contraceptives; they minimize compliance, while maximize effectiveness. They comprise subdermal implants and intrauterine devices. Other long-acting agents exist, such as Depo Provera and Noristerat. Use of Depo Provera and Noristerat carries great effectiveness, good clinical safety and usefulness in developing countries. They cause no significant increase in breast cancer risk, but they may carry an increased risk of HIV. Subcutaneous delivery systems have two common features: prolongation of effect is obtained by a drug reservoir and for most of their duration of action they provide a continuous, sustained release of the active hormone. Finally, the intrauterine system Mirena represents both a very effective contraceptive and a specific treatment for menorrhagia.

  16. Familiarity with and Preferences for Oral and Long-Acting Injectable HIV Pre-exposure Prophylaxis (PrEP) in a National Sample of Gay and Bisexual Men in the U.S.

    PubMed

    Parsons, Jeffrey T; Rendina, H Jonathon; Whitfield, Thomas H F; Grov, Christian

    2016-07-01

    We sought to determine preferences for oral versus long-acting injectable (LAI) PrEP among gay and bisexual men (GBM). We surveyed a national U.S. sample of 1071 GBM about forms of PrEP. LAI PrEP was found to be acceptable among 43.2 % of men when injected monthly compared with 53.6 % of men when injected every 3 months. When asked to choose between forms of PrEP, 46.0 % preferred LAI, 14.3 % oral, 21.7 % whichever was most effective, 10.1 % had no preference, and 7.8 % would not take PrEP. There were no differences in PrEP preferences by race/ethnicity, income, region of residence, or relationship status. Those unwilling to take PrEP were significantly older than those who preferred LAI PrEP and those who would take either. Those who preferred the most effective form were younger, had less education, and reported more recent club drug use. Those who reported condomless anal sex and those who thought they were good PrEP candidates were more willing to take PrEP. Long-term health and side effects were of the greatest concern for both LAI and oral PrEP. The availability of LAI PrEP has the potential to increase uptake among GBM. The results of ongoing clinical trials of LAI PrEP will need to demonstrate similar or greater efficacy as daily Truvada for uptake to be maximized.

  17. A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype-3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells

    PubMed Central

    LIU, YUAN-HUA; WU, SONG-ZE; WANG, GANG; HUANG, NI-WEN; LIU, CHUN-TAO

    2015-01-01

    The persistent administration of β2-adrenergic (β2AR) agonists has been demonstrated to increase the risk of severe asthma, partly due to the induction of tolerance to bronchoprotection via undefined mechanisms. The present study investigated the potential effect of the long-acting β2-adrenergic agonist, formoterol, on the expression of muscarinic M3 receptor (M3R) in rat airway smooth muscle cells (ASMCs). Primary rat ASMCs were isolated and characterized following immunostaining with anti-α-smooth muscle actin antibodies. The protein expression levels of M3R and phospholipase C-β1 (PLCβ1) were characterized by western blot analysis and the production of inositol 1,4,5-trisphosphate (IP3) was determined using an enzyme-linked immunosorbent assay. Formoterol increased the protein expression of M3R in rat ASMCs in a time- and dose-dependent manner, which was significantly inhibited by the β2AR antagonist, ICI118,551 and the cyclic adenosine monophosphate (cAMP) inhibitor, SQ22,536. The increased protein expression of M3R was positively correlated with increased production of PLCβ1 and IP3. Furthermore, treatment with the glucocorticoid, budesonide, and the PLC inhibitor, U73,122, significantly suppressed the formoterol-induced upregulated protein expression levels of M3R and PLCβ1 and production of IP3. The present study demonstrated that formoterol mediated the upregulation of M3R in the rat ASMCs by activating the β2AR-cAMP signaling pathway, resulting in increased expression levels of PLCβ1 and IP3, which are key to inducing bronchoprotection tolerance. Administration of glucocorticoids or a PLC antagonist prevented formoterol-induced bronchoprotection tolerance by suppressing the protein expression of M3R. PMID:25672589

  18. Benzydamine Oral Spray Inhibiting Parasympathetic Function of Tracheal Smooth Muscle

    PubMed Central

    Chao, Pin-Zhir; Lee, Fei-Peng

    2015-01-01

    Objectives Benzydamine is a nonsteroidal anti-inflammatory agents agent with anti-inflammatory and local anesthesia properties that is available in the entire world as an oral spray for oral mucositis patients who are suffering from radiation effects. The effect of benzydamine on oral mucositis in vivo is well known; however, the effect of the drug on tracheal smooth muscle has rarely been explored. During administration of the benzydamine for oral symptoms, it might affect the trachea via oral intake or inhalation. Methods We examined the effectiveness of benzydamine on isolated rat tracheal smooth muscle. The following assessments of benzydamine were performed: effect on tracheal smooth muscle resting tension; effect on contraction caused by 10-6M methacholine as a parasympathetic mimetic; and effect of the drug on electrically induced tracheal smooth muscle contractions. Results Addition of methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of benzydamine at doses of 10-5M or above elicited a significant relaxation response to 10-6M methacholine-induced contraction. Benzydamine could inhibit electrical field stimulation-induced spike contraction. It alone had a minimal effect on the basal tension of trachea as the concentration increased. Conclusion This study indicated that high concentrations of benzydamine might actually inhibit parasympathetic function of the trachea. Benzydamine might reduce asthma attacks in oral mucositis patients because it could inhibit parasympathetic function and reduce methacholine-induced contraction of tracheal smooth muscle. PMID:25729498

  19. Long-Acting Growth Hormone: An Update.

    PubMed

    Saenger, Paul H; Mejia-Corletto, Jorge

    2016-01-01

    After the introduction of recombinant human growth hormone (rhGH) in 1985, a myriad of children and adults have benefited from its growth-promoting and metabolic effects. Nowadays, current therapeutic regimens rely on daily subcutaneous GH injections that could be burdensome and inconvenient to pediatric patients. As expected with any long-term parenteral pharmacological treatment, these daily regimens may promote nonadherence, poor compliance, treatment abandonment and/or suboptimal clinical outcomes. In order to improve patient and caregiver acceptance of proposed regimens, simplified dosing schedules could potentially aid in reducing poor compliance and maximize the therapeutic end results. Long-acting GH formulations have been designed and perfected over the last two decades, and currently there are several formulations in advanced stages of research as a reasonable attempt to improve patient's adherence to GH treatment. A long-acting GH preparation allowing for reduced injection frequency is likely to improve treatment adherence and to decrease the distress and inconvenience associated with daily injections. This review presents an update about the status of current and recent efforts that have enabled the formulation of sustained-release, long-acting rhGH as it has been longed for many years in the pediatric endocrinology field.

  20. A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype‑3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells.

    PubMed

    Liu, Yuan-Hua; Wu, Song-Ze; Wang, Gang; Huang, Ni-Wen; Liu, Chun-Tao

    2015-06-01

    The persistent administration of β2‑adrenergic (β2AR) agonists has been demonstrated to increase the risk of severe asthma, partly due to the induction of tolerance to bronchoprotection via undefined mechanisms. The present study investigated the potential effect of the long‑acting β2‑adrenergic agonist, formoterol, on the expression of muscarinic M3 receptor (M3R) in rat airway smooth muscle cells (ASMCs). Primary rat ASMCs were isolated and characterized following immunostaining with anti‑α‑smooth muscle actin antibodies. The protein expression levels of M3R and phospholipase C‑β1 (PLCβ1) were characterized by western blot analysis and the production of inositol 1,4,5‑trisphosphate (IP3) was determined using an enzyme‑linked immunosorbent assay. Formoterol increased the protein expression of M3R in rat ASMCs in a time‑ and dose‑dependent manner, which was significantly inhibited by the β2AR antagonist, ICI118,551 and the cyclic adenosine monophosphate (cAMP) inhibitor, SQ22,536. The increased protein expression of M3R was positively correlated with increased production of PLCβ1 and IP3. Furthermore, treatment with the glucocorticoid, budesonide, and the PLC inhibitor, U73,122, significantly suppressed the formoterol‑induced upregulated protein expression levels of M3R and PLCβ1 and production of IP3. The present study demonstrated that formoterol mediated the upregulation of M3R in the rat ASMCs by activating the β2AR‑cAMP signaling pathway, resulting in increased expression levels of PLCβ1 and IP3, which are key to inducing bronchoprotection tolerance. Administration of glucocorticoids or a PLC antagonist prevented formoterol‑induced bronchoprotection tolerance by suppressing the protein expression of M3R. PMID:25672589

  1. [The oral sucker muscles of six representatives of the order Paramphistomatida (Plathelminthes, Trematoda)].

    PubMed

    Burdakova, E N; Yastrebova, I V; Yastrebov, M V

    2015-01-01

    The spatial arrangement of muscles in the oral suckers of six trematode species belonging to five families of the order Paramphistomatida is described. The functional load and adaptive significance of different muscle groups in the suckers themselves and the associated structures--preoral lip and muscular cap--are discussed. Complete section series in three projections have been examined; this demonstrates the presence of previously unnoticed structures, namely, semicircular and diagonal muscles, regulating shape of the oral cavity, and short longitudinal muscles, acting as a sphincter, as well as localization of the largest internal muscles on the sucker lateral sides. It has been shown that the presence of internal longitudinal muscles suggests that the organs in question are closer to the oral suckers of other trematodes rather than to their pharynxes.

  2. Long Acting Risperidone in an Adolescent with Conduct Disorder: A Case Report

    PubMed Central

    Tutkunkardaş, Mustafa Deniz; Abali, Osman

    2011-01-01

    Adolescent conduct disorder (CD) is generally hard to manage clinically, as this population often refuses to take oral medications. Families and acquaintances of these adolescents usually suffer from extreme psychological, financial and social difficulties. Oral antipsychotics are the primary drugs of choice clinically, after behavioral treatments. Here we report a case with attention deficit hyperactivity disorder and conduct disorder who refuses to take any medications, was not eligible for behavioral treatments and was treated successfully with long acting risperidone.

  3. Long-acting methods require special care.

    PubMed

    Blaney, C L

    1994-08-01

    Long-acting contraceptive methods including IUDs, implants, and sterilization are among the most effective and convenient contraceptive methods, requiring little or no effort on the part of the user once provided by a trained healthcare provider. Some women, however, oppose the development and use of provider-dependent contraceptive methods due to the potential for method misuse. These methods, for example, could be provided without women's fully informed choice, access to removal could be blocked, or the method could be provided to an inappropriate client. Making a contraceptive method unavailable because of potential abuse instead restricts women's reproductive choices. After all, abuse generally comes from the legal or delivery system, not from the method itself. Efforts should be made to satisfy users with standard norms for performance and without targets for specific methods. Good service delivery along with revised approaches to contraceptive introduction and program evaluation can help prevent inappropriate method use and ensure that women receive adequate information and counseling to help them make reproductive choices without undue influence. The author discusses Norplant delivery, providing IUDs, offering sterilization, and improving access.

  4. Long-term use of short- and long-acting nitrates in stable angina pectoris.

    PubMed

    Kosmicki, Marek Antoni

    2009-05-01

    Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

  5. Effect of oral appliances on genioglossus muscle tonicity seen with diffusion tensor imaging: A pilot study

    PubMed Central

    Shinagawa, Hideo; Murano, Emi Z.; Zhuo, Jiachen; Landman, Bennett; Gullapalli, Rao P.; Prince, Jerry L.; Stone, Maureen

    2010-01-01

    Objective The purpose of this study was to examine whether the diffusion tensor imaging (DTI) technique can be used as a modality to represent the structural deformation in the in vivo genioglossus (GG) muscle fibers with oral appliances (OAs). Study Design Three healthy subjects were recruited for the pilot study. A custom-made OA, which is modified from a tongue retaining device (TRD), was constructed for each subject before the DTI acquisitions. Recordings were made with and without OAs to compare the GG muscle fiber deformation. Result DTI provided good resolution of tongue muscle fibers in vivo and successful isolation of each muscle fiber bundle. In particular, the GG muscle fiber deformation due to OAs was clearly visualized. Conclusions This DTI technique may be used not only to identify the individual myoarchitecture, but also to assess muscle fiber deformations in vivo, such as constriction, dilatation, and rotation with OAs. Clinical studies for OSA patients will be the next step. PMID:19217012

  6. Aripiprazole Lauroxil Long-Acting Injectable: The Latest Addition to Second-Generation Long-Acting Agents.

    PubMed

    Aggarwal, Arpit; Gopalakrishna, Ganesh; Lauriello, John

    2016-01-01

    Antipsychotics have long been the mainstay for the treatment of schizophrenia and other psychotic disorders. Long-acting injectables (LAI) of antipsychotics-provided once every two weeks to once every three months-promise to reduce the incidence of nonadherence. ARISTADA(™) (aripiprazole lauroxil; ALLAI) extended-release injectable suspension was approved by the U.S. Food and Drug Administration in October 2015 for the treatment of schizophrenia, and is the newest entrant in the LAI market. ALLAI is available as a single-use, pre-filled syringe, can be started in three different dosages, and also has the option of every six-week dosing. Treatment with oral aripiprazole is recommended for the first twenty-one days after the first ALLAI injection, which is a potential disadvantage. Adverse effects include sensitivity to extrapyramidal symptoms, especially akathisia, which is well documented in other aripiprazole preparations. There is no available data comparing ALLAI to other antipsychotics, and more head-to-head trials comparing different LAI formulations are needed. Based on the available data, ALLAI is an effective and safe option for treatment of schizophrenia. Further studies and post-marketing data will provide better understanding of this formulation. PMID:27074333

  7. Oral Dosing of Chemical Indicators for In Vivo Monitoring of Ca2+ Dynamics in Insect Muscle

    PubMed Central

    Ferdinandus; Arai, Satoshi; Ishiwata, Shin’ichi; Suzuki, Madoka; Sato, Hirotaka

    2015-01-01

    This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action) and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing). A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects. PMID:25590329

  8. Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in insect muscle.

    PubMed

    Ferdinandus; Arai, Satoshi; Ishiwata, Shin'ichi; Suzuki, Madoka; Sato, Hirotaka

    2015-01-01

    This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action) and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing). A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects. PMID:25590329

  9. Oral Gingival Cell Cigarette Smoke Exposure Induces Muscle Cell Metabolic Disruption

    PubMed Central

    Baeder, Andrea C.; Napa, Kiran; Richardson, Sarah T.; Taylor, Oliver J.; Andersen, Samantha G.; Wilcox, Shalene H.; Winden, Duane R.; Reynolds, Paul R.

    2016-01-01

    Cigarette smoke exposure compromises health through damaging multiple physiological systems, including disrupting metabolic function. The purpose of this study was to determine the role of oral gingiva in mediating the deleterious metabolic effects of cigarette smoke exposure on skeletal muscle metabolic function. Using an in vitro conditioned medium cell model, skeletal muscle cells were incubated with medium from gingival cells treated with normal medium or medium containing suspended cigarette smoke extract (CSE). Following incubation of muscle cells with gingival cell conditioned medium, muscle cell mitochondrial respiration and insulin signaling and action were determined as an indication of overall muscle metabolic health. Skeletal muscle cells incubated with conditioned medium of CSE-treated gingival cells had a profound reduction in mitochondrial respiration and respiratory control. Furthermore, skeletal muscle cells had a greatly reduced response in insulin-stimulated Akt phosphorylation and glycogen synthesis. Altogether, these results provide a novel perspective on the mechanism whereby cigarette smoke affects systemic metabolic function. In conclusion, we found that oral gingival cells treated with CSE create an altered milieu that is sufficient to both disrupted skeletal muscle cell mitochondrial function and insulin sensitivity. PMID:27034671

  10. Development of oral and branchial muscles in lancelet larvae of Branchiostoma japonicum.

    PubMed

    Yasui, Kinya; Kaji, Takao; Morov, Arseniy R; Yonemura, Shigenobu

    2014-04-01

    The perforated pharynx has generally been regarded as a shared characteristic of chordates. However, there still remains phylogenetic ambiguity between the cilia-driven system in invertebrate chordates and the muscle-driven system in vertebrates. Giant larvae of the genus Asymmetron were reported to develop an orobranchial musculature similar to that of vertebrates more than 100 years ago. This discovery might represent an evolutionary link for the chordate branchial system, but few investigations of the lancelet orobranchial musculature have been completed since. We studied staged larvae of a Japanese population of Branchiostoma japonicum to characterize the developmental property of the orobranchial musculature. The larval mouth and the unpaired primary gills develop well-organized muscles. These muscles function only as obturators of the openings without antagonistic system. As the larval mouth enlarged posteriorly to the level of the ninth myomere, the oral musculature was fortified accordingly without segmental patterning. In contrast, the iterated branchial muscles coincided with the dorsal myomeric pattern before metamorphosis, but the pharynx was remodeled dynamically irrespective of the myomeric pattern during metamorphosis. The orobranchial musculature disappeared completely during metamorphosis, and adult muscles in the oral hood and velum, as well as on the pterygial coeloms developed independently. The lancelet orobranchial musculature is apparently a larval adaptation to prevent harmful intake. However, vestigial muscles appeared transiently with the secondary gill formation suggest a bilateral ancestral state of muscular gills, and a segmental pattern of developing branchial muscles without neural crest and placodal contributions is suggestive of a precursor of vertebrate branchiomeric pattern.

  11. [Intravenous regional anesthesia with long-acting local anesthetics. An update].

    PubMed

    Atanassoff, P G; Lobato, A; Aguilar, J L

    2014-02-01

    Intravenous regional anesthesia is a widely used technique for brief surgical interventions, primarily on the upper limbs and less frequently, on the lower limbs. It began being used at the beginning of the 20th century, when Bier injected procaine as a local anesthetic. The technique to accomplish anesthesia has not changed much since then, although different drugs, particularly long-acting local anesthetics, such as ropivacaine and levobupivacaine in low concentrations, were introduced. Additionally, drugs like opioids, muscle relaxants, paracetamol, neostigmine, magnesium, ketamine, clonidine, and ketorolac, have all been investigated as adjuncts to intravenous regional anesthesia, and were found to be fairly useful in terms of an increased onset of operative anesthesia and longer lasting perioperative analgesia. The present article provides an overview of current knowledge with emphasis on long-acting local anesthetic drugs. PMID:24156887

  12. Long-Acting Injectable Antipsychotics for Prevention of Relapse in Bipolar Disorder: A Systematic Review and Meta-Analyses of Randomized Controlled Trials

    PubMed Central

    Oya, Kazuto; Iwata, Nakao

    2016-01-01

    Background: This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Methods: Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. Results: We identified 7 randomized controlled trials (n=1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials)=449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents=283]; and placebo=284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio=0.63, P<.0001), relapse of manic symptoms (risk ratio=0.42, P<.00001), and all-cause discontinuation (risk ratio=0.75, P=.007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio=4.82, P=.001) and weight gain (risk ratio=3.80, P<.0001) than placebo. The pooled long-acting injectable antipsychotics did not outperform oral medications regarding primary outcome but with significant heterogeneity (I2=74%). Sensitivity analysis, including only studies with rapid cycling or high frequency of relapse patients, revealed that long-acting injectable antipsychotics were superior compared to oral medications (I2=0%, RR=0.58, P=.0004). However, the comparators in this sensitivity analysis did not include second-generation antipsychotic monotherapy. In sensitivity analysis, including only studies with second-generation antipsychotic monotherapy as the comparator, long-acting injectable antipsychotics did not outperform second

  13. Oral muscles are progressively affected in Duchenne muscular dystrophy: implications for dysphagia treatment.

    PubMed

    van den Engel-Hoek, Lenie; Erasmus, Corrie E; Hendriks, Jan C M; Geurts, Alexander C H; Klein, Willemijn M; Pillen, Sigrid; Sie, Lilian T; de Swart, Bert J M; de Groot, Imelda J M

    2013-05-01

    Dysphagia is reported in advanced stages of Duchenne muscular dystrophy (DMD). The population of DMD is changing due to an increasing survival. We aimed to describe the dysphagia in consecutive stages and to assess the underlying mechanisms of dysphagia in DMD, in order to develop mechanism based recommendations for safe swallowing. In this cross-sectional study, participants were divided into: early and late ambulatory stage (AS, n = 6), early non-ambulatory stage (ENAS, n = 7), and late non-ambulatory stage (LNAS, n = 11). Quantitative oral muscle ultrasound was performed to quantify echo intensity. Swallowing was assessed with a video fluoroscopic swallow study, surface electromyography (sEMG) of the submental muscle group and tongue pressure. Differences in outcome parameters among the three DMD stages were tested with analysis of variance. Oral muscles related to swallowing were progressively affected, starting in the AS with the geniohyoid muscle. Tongue (pseudo) hypertrophy was found in 70 % of patients in the ENAS and LNAS. Oral phase problems and post-swallow residue were observed, mostly in the LNAS with solid food. sEMG and tongue pressure data of swallowing solid food revealed the lowest sEMG amplitude, the longest duration and lowest tongue pressure in the LNAS. In case of swallowing problems in DMD, based on the disturbed mechanisms of swallowing, it is suggested to (1) adjust meals in terms of less solid food, and (2) drink water after meals to clear the oropharyngeal area.

  14. Characterization of muscle alteration in oral submucous fibrosis-seeking new evidence

    PubMed Central

    Urs, Aadithya-Basavaraj; Augustine, Jeyaseelan; Kumar, Priya

    2015-01-01

    Background The aim of the study was to assess the progression of Oral Submucous Fibrosis (OSF) by investigating the correlation between clinical mouth opening and muscle-epithelial distance in tissue sections. Characterization of changes involving muscle was ascertained. Material and Methods 50 cases and 10 controls were included in this case-control study. Inter-incisal mouth opening was measured and classified according to Lai et al. as Group A (more than 35mm), Group B (30 to 35mm), Group C (20 to 30mm), Group D (less than 20mm). Histopathological sections were graded as very early, early, moderately advanced, advanced OSF. Muscle-epithelial distance was calculated using image analysis software. The four most common degenerative changes observed in muscles, namely fragmentation, highly eosinophilic areas with loss of striations, nucleus internalization and multiple pyknotic nuclei were also assessed. Results Comparisons of muscle-epithelial distance were made between the clinical and histopathological groups to those of controls. The mean muscle-epithelial distance was: Group A-626.8±309.36 µm, B-827.5±549.72 µm, C-673.2±321.93 µm, D-439.9±173.84µm, Controls-1222.19 ±441.7µm. Post-hoc Bonferroni Test revealed a statistically significant reduction in the muscle-epithelial distance in Group C (p-value = 0.001) and D (p-value = 0.001) as compared to controls. The mean muscle-epithelial distance in very early, early, moderately advanced and advanced OSF was 732.73±232.81µm, 726.54±361.63 µm, 548.36±273.13 and 172.40±58.41 µm respectively. Highly significant difference in muscle-epithelial distance was seen between controls as compared to early (p-value =0.002), moderately advanced (p-value = 0.001) and advanced OSF (p-value = 0.001. Fragmentation and highly eosinophilic areas were invariably noticed in advanced OSF. Multiple pyknotic nuclei were variable with no specificity. Conclusions Reduction in muscle-epithelial distance may prove to be a

  15. Effect of neuromuscular electrical stimulation on facial muscle strength and oral function in stroke patients with facial palsy

    PubMed Central

    Choi, Jong-Bae

    2016-01-01

    [Purpose] The aim of this study was to investigate the effect of neuromuscular electrical stimulation on facial muscle strength and oral function in stroke patients with facial palsy. [Subjects and Methods] Nine subjects received the electrical stimulation and traditional dysphagia therapy. Electrical stimulation was applied to stimulate each subject’s facial muscles 30 minutes a day, 5 days a week, for 4 weeks. [Results] Subjects showed significant improvement in cheek and lip strength and oral function after the intervention. [Conclusion] This study demonstrates that electrical stimulation improves facial muscle strength and oral function in stroke patients with dysphagia. PMID:27799689

  16. Moral and policy issues in long-acting contraception.

    PubMed

    Brown, G F; Moskowitz, E H

    1997-01-01

    The advent of reversible long-acting contraceptives-IUDs, injectables and implants-has provided women throughout the world with valuable new fertility regulation options. These highly effective methods, together with male and female sterilization, have proven to be enormously popular and are now used by the majority of women and men who are currently contracepting worldwide. Despite their remarkable popularity, long-acting contraceptives have engendered considerable controversy. Political, ethical, and safety questions have emerged, stemming from the ways in which these contraceptives have been developed and used over the course of this century. At the heart of the concern is the issue of reproductive rights and freedom. This paper reviews the history of the development of long-acting contraceptives, including the prospect of new methods that will likely emerge from ongoing research and development. It also examines the history, in the United States and in developing countries, of the use and abuse of long-acting methods, including sterilization, in the context of eugenics and population control policies. It then describes a new paradigm of reproductive health and rights that has emerged from the International Conference on Population Development in Cairo, and which offers an enlightened approach to future policies and programs. In light of the wide variety of ways in which long-acting contraceptives have been provided, the paper examines the rights and responsibilities of governments, family planning providers, and individuals. An ethical framework for the use of long-acting methods is discussed, and public policies for the future are proposed.

  17. Clinical blood chemistry values and long acting phenothiazines.

    PubMed

    Schneider, S J; Kirby, E J; Itil, T M

    1981-05-01

    Fifty-nine chronic schizophrenic patients received one year of treatment with either fluphenazine enanthate or pipothiazine palmitate IM. Both long acting neuroleptics significantly decreased serum albumin, total protein and creatinine values. Triglycerides were decreased only early in treatment. Pretreatment findings from therapy responders, as compared with those who failed to respond to treatment, included higher albumin values and to a lesser extent, lower lactic dehydrogenase values and greater height. These results were discussed with an eye toward the hepatocellular effects of long acting phenothiazines and the effect of liver function on the pharmacokinetics of these medications. PMID:6114503

  18. Clinical blood chemistry values and long acting phenothiazines.

    PubMed

    Schneider, S J; Kirby, E J; Itil, T M

    1981-05-01

    Fifty-nine chronic schizophrenic patients received one year of treatment with either fluphenazine enanthate or pipothiazine palmitate IM. Both long acting neuroleptics significantly decreased serum albumin, total protein and creatinine values. Triglycerides were decreased only early in treatment. Pretreatment findings from therapy responders, as compared with those who failed to respond to treatment, included higher albumin values and to a lesser extent, lower lactic dehydrogenase values and greater height. These results were discussed with an eye toward the hepatocellular effects of long acting phenothiazines and the effect of liver function on the pharmacokinetics of these medications.

  19. Development of oral and branchial muscles in lancelet larvae of Branchiostoma japonicum.

    PubMed

    Yasui, Kinya; Kaji, Takao; Morov, Arseniy R; Yonemura, Shigenobu

    2014-04-01

    The perforated pharynx has generally been regarded as a shared characteristic of chordates. However, there still remains phylogenetic ambiguity between the cilia-driven system in invertebrate chordates and the muscle-driven system in vertebrates. Giant larvae of the genus Asymmetron were reported to develop an orobranchial musculature similar to that of vertebrates more than 100 years ago. This discovery might represent an evolutionary link for the chordate branchial system, but few investigations of the lancelet orobranchial musculature have been completed since. We studied staged larvae of a Japanese population of Branchiostoma japonicum to characterize the developmental property of the orobranchial musculature. The larval mouth and the unpaired primary gills develop well-organized muscles. These muscles function only as obturators of the openings without antagonistic system. As the larval mouth enlarged posteriorly to the level of the ninth myomere, the oral musculature was fortified accordingly without segmental patterning. In contrast, the iterated branchial muscles coincided with the dorsal myomeric pattern before metamorphosis, but the pharynx was remodeled dynamically irrespective of the myomeric pattern during metamorphosis. The orobranchial musculature disappeared completely during metamorphosis, and adult muscles in the oral hood and velum, as well as on the pterygial coeloms developed independently. The lancelet orobranchial musculature is apparently a larval adaptation to prevent harmful intake. However, vestigial muscles appeared transiently with the secondary gill formation suggest a bilateral ancestral state of muscular gills, and a segmental pattern of developing branchial muscles without neural crest and placodal contributions is suggestive of a precursor of vertebrate branchiomeric pattern. PMID:24301696

  20. Long-acting injectable antipsychotics in the elderly: guidelines for effective use.

    PubMed

    Masand, Prakash S; Gupta, Sanjay

    2003-01-01

    The elderly are at increased risk for psychosis because of age-related deterioration of cortical areas and neurochemical changes, comorbid physical illnesses, social isolation, sensory deficits and polypharmacy. The prevalence of psychiatric and neuropsychiatric disorders requiring treatment with an antipsychotic agent is expected to increase dramatically among people aged >64 years. Antipsychotic agents are effective in the treatment of schizophrenia, schizoaffective disorder, behavioural symptoms in patients with dementia, and mood disorders with psychosis. However, failure to adhere to a prescribed medication regimen by patients with psychosis is one of the most frustrating problems faced by mental healthcare providers, because of the high risk of relapse associated with partial compliance. For patients with psychosis who will not or cannot take oral medications on a regular daily basis or have other characteristics, such as memory, vision or auditory impairment, which contribute to partial compliance, long-acting injectable antipsychotic medication offers a solution. Older patients are especially at risk of adverse effects associated with traditional antipsychotic agents, such as motor effects, postural hypotension, excessive sedation, and anticholinergic effects because of age-related pharmacokinetic and pharmacodynamic factors, coexisting medical illnesses and concomitant medications. Therefore, drug dosage recommendations in the elderly are much more conservative than in younger patients. The appropriate starting dose of an antipsychotic in older individuals is 25% of the usual adult dose; total daily maintenance doses ranges from 25-50% of the adult dose. There are few studies regarding the use of depot antipsychotics in elderly patients. Studies that are available indicate that traditional antipsychotic agents given as depot injections are associated with positive outcomes in the elderly. Because the risks for extrapyramidal symptoms and tardive dyskinesia

  1. Striated muscle involvement in experimental oral infection by herpes simplex virus type 1.

    PubMed

    Gonzalez, María Inés; Sanjuan, Norberto A

    2013-07-01

    Herpes simplex virus type 1 is one of the most frequent causes of oral infection in humans, especially during early childhood. Several experimental models have been developed to study the pathogenesis of this virus but all of them employed adult animals. In this work, we developed an experimental model that uses mice younger than 4 days old, to more closely resemble human infection. Mice were infected subcutaneously with the prototype strain McIntyre of Herpes simplex-1, and the progression of infection was studied by immunoperoxidase. All animals died within 24-72 h post-infection, while viral antigens were found in the oral epithelium, nerves and brain. The most striking result was the finding of viral antigens in the nucleus and cytoplasm of cells belonging to striated muscles. Organotypic cultures of striated muscles were performed, and viral replication was observed in them by immunocytochemistry, electron microscopy and viral isolation. We conclude that the infection of striated muscles is present from the onset of oral infection and, eventually, could explain some clinical observations in humans.

  2. Use of long-acting reversible contraceptives to reduce the rate of teen pregnancy.

    PubMed

    Rome, Ellen

    2015-11-01

    Long-acting reversible contraceptives (LARCs) are safe for use in adolescents and do not rely on compliance or adherence for effectiveness. Continuation rates are higher and pregnancy rates are lower for adolescent users of LARCs compared with short-acting methods such as oral contraceptives. Similarly, repeat pregnancy rates are lower when LARCs are used compared with other forms of contraception. Myths and misconceptions about LARCs and other contraceptives remain a barrier to their use. Health care providers are in a unique position to provide confidential care to adolescents, and should provide education to them about the various contraceptive options, especially LARCs.

  3. Narcotic tapering in pregnancy using long-acting morphine

    PubMed Central

    Dooley, Roisin; Dooley, Joe; Antone, Irwin; Guilfoyle, John; Gerber-Finn, Lianne; Kakekagumick, Kara; Cromarty, Helen; Hopman, Wilma; Muileboom, Jill; Brunton, Nicole; Kelly, Len

    2015-01-01

    Abstract Objective To document the management of and outcomes for patients receiving narcotic replacement and tapering with long-acting morphine preparations during pregnancy. Design A prospective cohort study over 18 months. Setting Northwestern Ontario. Participants All 600 births at Meno Ya Win Health Centre in Sioux Lookout, Ont, from January 1, 2012, to June 30, 2013, including 166 narcotic-exposed pregnancies. Intervention Narcotic replacement and tapering of narcotic use with long-acting morphine preparations. Main outcome measures Prenatal management of maternal narcotic use, incidence of neonatal abstinence syndrome, and other neonatal outcomes. Results The incidence of neonatal abstinence syndrome fell significantly to 18.1% of pregnancies exposed to narcotics (from 29.5% in a previous 2010 study, P = .003) among patients using narcotic replacement and tapering with long-acting morphine preparations. Neonatal outcomes were otherwise equivalent to those of the nonexposed pregnancies. Conclusion In many patients, long-acting morphine preparations can be safely used and tapered in pregnancy, with a subsequent decrease in observed neonatal withdrawal symptoms. PMID:25821873

  4. Alterations in 18F-FDG accumulation into neck-related muscles after neck dissection for patients with oral cancers

    PubMed Central

    Kito, Shinji; Koga, Hirofumi; Kodama, Masaaki; Habu, Manabu; Kokuryo, Shinya; Oda, Masafumi; Matsuo, Kou; Nishino, Takanobu; Matsumoto-Takeda, Shinobu; Uehara, Masataka; Yoshiga, Daigo; Tanaka, Tatsurou; Nishimura, Shun; Miyamoto, Ikuya; Sasaguri, Masaaki; Tominaga, Kazuhiro; Yoshioka, Izumi; Morimoto, Yasuhiro

    2016-01-01

    Background 18F-fluoro-2-deoxy-D-glucose (18F-FDG) accumulations are commonly seen in the neck-related muscles of the surgical and non-surgical sides after surgery with neck dissection (ND) for oral cancers, which leads to radiologists having difficulty in diagnosing the lesions. To examine the alterations in 18F-FDG accumulation in neck-related muscles of patients after ND for oral cancer. Material and Methods 18F-FDG accumulations on positron emission tomography (PET)-computed tomography (CT) in neck-related muscles were retrospectively analyzed after surgical dissection of cervical lymph nodes in oral cancers. Results According to the extent of ND of cervical lymph nodes, the rate of patients with 18F-FDG-PET-positive areas increased in the trapezius, sternocleidomastoid, and posterior neck muscles of the surgical and/or non-surgical sides. In addition, SUVmax of 18F-FDG-PET-positive areas in the trapezius and sternocleidomastoid muscles were increased according to the extent of the ND. Conclusions In evaluating 18F-FDG accumulations after ND for oral cancers, we should pay attention to the 18F-FDG distributions in neck-related muscles including the non-surgical side as false-positive findings. Key words:18F-FDG, PET-CT, oral cancers, muscles. PMID:27031062

  5. Two cases of long-acting paliperidone in adolescence

    PubMed Central

    Fàbrega, Marina; Sugranyes, Gisela; Baeza, Inmaculada

    2015-01-01

    Paliperidone palmitate long-acting injection (PPLAI) is an atypical antipsychotic agent currently approved by the European Medicine Agency for the acute and maintenance treatment of schizophrenia in adults. However, there is no information so far on safety and effectiveness in patients under 18 years of age. We report on two clinical cases of adolescents with a psychotic spectrum disorder treated with PPLAI in an inpatient setting. The cases illustrate that PPLAI may hold potential as an effective and acceptably tolerated antipsychotic drug in adolescents with psychotic spectrum disorders. Given the lack of approved long acting injectable antipsychotics in patients under 18 years of age, reports on the effectiveness and safety of such medications in children and adolescent patients are of importance. PMID:26557986

  6. Status of long-acting-growth hormone preparations--2015.

    PubMed

    Høybye, Charlotte; Cohen, Pinchas; Hoffman, Andrew R; Ross, Richard; Biller, Beverly M K; Christiansen, Jens Sandahl

    2015-10-01

    Growth hormone (GH) treatment has been an established therapy for GH deficiency (GHD) in children and adults for more than three decades. Numerous studies have shown that GH treatment improves height, body composition, bone density, cardiovascular risk factors, physical fitness and quality of life and that the treatment has few side effects. Initially GH was given as intramuscular injections three times per week, but daily subcutaneous injections were shown to be more effective and less inconvenient and the daily administration has been used since its introduction in the 1980s. However, despite ongoing improvements in injection device design, daily subcutaneous injections remain inconvenient, painful and distressing for many patients, leading to noncompliance, reduced efficacy and increased health care costs. To address these issues a variety of long-acting formulations of GH have been developed. In this review we present the current status of long-acting GH preparations and discuss the specific issues related to their development.

  7. A Systemic Review and Experts’ Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder

    PubMed Central

    Chou, Yuan Hwa; Chu, Po-Chung; Wu, Szu-Wei; Lee, Jen-Chin; Lee, Yi-Hsuan; Sun, I-Wen; Chang, Chen-Lin; Huang, Chien-Liang; Liu, I-Chao; Tsai, Chia-Fen; Yen, Yung-Chieh

    2015-01-01

    Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms. PMID:26243837

  8. Do rhythms exist in elbow flexor torque, oral temperature and muscle thickness during normal waking hours?

    PubMed

    Buckner, Samuel L; Dankel, Scott J; Counts, Brittany R; Barnett, Brian E; Jessee, Matthew B; Mouser, J Grant; Halliday, Tanya M; Loenneke, Jeremy P

    2016-06-01

    The purpose of the current study was to examine the influence of "time" on isometric elbow flexion torque, body temperature and muscle size without interrupting the sleep wake cycle in college aged males. Two hours following the participants normal wake time, oral temperature was measured, followed by muscle thickness of the upper and lower body using ultrasound, as well as elbow flexor torque via a maximal voluntary contraction (MVC). Measurements were repeated every 2h for 12h (Time points 1-7). To examine the repeatability of the rhythm, participants returned and completed the same procedures as before within 14days of their first circadian visit (Circadian visit 2). There was no time×day interaction for body temperature (p=0.29), nor were there main effects for time (p=0.15) or day (p=0.74). For MVC, there was no time×day interaction (p=0.93) or main effect for day (p=0.50), however, there was a main effect for time (p=0.01). MVC at time points 1 (86.4±6.4Nm) and 2 (87.1±6.2Nm) was greater than time points 4 (84.2±6.6Nm) and 6 (83.4±6.8Nm, p<0.05). Additionally, time point 5 MVC was greater than time point 4. For upper body muscle thickness, there was no time×day interaction (p=0.34), nor was there a main effect for day (p=0.38), or time (p=0.06). For lower body muscle thickness, there was no time×day interaction (p=0.57), nor was there a main effect for day (p=0.75), or time (p=0.13). Cosinor analyses revealed no group level rhythms for oral temperature, muscle thickness or strength (p>0.05), however, there were some individual rhythms noted for muscle thickness and strength. Results suggest that, when accounting for an individuals normal wake time, circadian rhythms of strength, temperature and muscle thickness are not apparent in most individuals.

  9. Effect of long-term therapy with oral steroids on respiratory muscle function and ventilatory drive.

    PubMed

    Zanotti, E; Corsico, R; Rampulla, C; Ambrosino, N; Fracchia, C; Crotti, P; Rubini, F; Nava, S

    1993-01-01

    It has been shown that chronic oral steroid therapy (ST) does not induce respiratory muscle dysfunction in normal and asthmatic subjects. As corticosteroids are sometimes chronically used in the treatment of the patients with chronic obstructive pulmonary disease (COPD), the aim of our study was to verify whether ST could cause respiratory muscle impairment and, since ST also affects the central nervous system, whether ST could influence the ventilatory pattern. We retrospectively studied 12 COPD patients (group A), on long-term therapy (for at least 4 consecutive months, range 4-18 months) with an oral steroid, deflazacort, 15 mg.d-1. The subjects were strictly matched, with regard to age, sex, height, weight, forced expiratory volume in one second (FEV1), residual volume (RV), arterial oxygen tension (PaCO2), arterial carbon dioxide tension (PaCO2) and pH, with 12 COPD patients (Group B) who had never taken oral steroids. To assess respiratory muscle strength, we measured maximal inspiratory (MIP) and expiratory (MEP) pressures, while mouth occlusion pressure (P0.1) was employed to assess neuromuscular drive; ventilatory pattern and airway impedence were also evaluated. Effectiveness of ST was confirmed by the plasmatic levels of endogenous cortisol. No significant differences were observed between the two groups with regard to MIP (A 72.2 +/- 9.7 vs B: 70 +/- 7.2 cmH2O) and MEP (A 91.6 +/- 10.5 vs B 94.4 +/- 7.6 cmH2O) whilst P0.1 was significantly higher in group A (2.6 +/- 0.3 cmH2O) than in group B (1.8 +/- 0.1 cmH2O). No significant differences were found among all the ventilatory parameters, but the impedence was significantly higher in group A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8472057

  10. Effectiveness of long-acting antipsychotics in clinical practice: 2. Effects of antipsychotic polypharmacy on risperidone long-acting injection and zuclopenthixol decanoate

    PubMed Central

    Cordiner, Matthew; Shajahan, Polash; McAvoy, Sarah; Bashir, Muhammad; Taylor, Mark

    2016-01-01

    Objectives: Antipsychotic polypharmacy (APP) is common clinical practice. Theoretically, APP runs the risk of additional side effects, drug interactions, adherence and cost. A limited evidence base is emerging to support the effectiveness of APP in clinical practice. Our companion paper highlighted the extent of APP alongside commonly prescribed long-acting antipsychotic injections (LAIs). We aimed to examine the effects of APP on discontinuation rates and Clinical Global Impression (CGI) outcomes in patients commenced on risperidone long-acting injection (RLAI) and zuclopenthixol decanoate. Method: LAI-naïve patients commenced on RLAI (n = 102) and zuclopenthixol decanoate(n = 105) were identified using our electronic patient record (running from 2002) within NHS Lanarkshire, Scotland, UK. This was a retrospective, electronic case note review with an 18-month follow up. Patient groups were divided into those receiving the LAI as the sole antipsychotic and those who were receiving additional oral antipsychotic polypharmacy (APP) for at least 50% of the duration of the treatment with their LAI. Kaplan–Meier statistics were calculated for discontinuation rates. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Antipsychotic polypharmacy occurred with RLAI (37%) and zuclopenthixol decanoate (46%) and was associated with lower discontinuation rates (statistical significant with zuclopenthixol for any cause and adverse effects discontinuation). APP had no adverse outcomes on hospital admissions or CGI ratings. Patients on APP did not have more severe, chronic or treatment resistant illnesses. Conclusions: For RLAI and zuclopenthixol decanoate, APP had some favourable outcomes when examining discontinuation rates for any cause, and adverse effects. This was unexpected as we had considered APP would signal illness chronicity and severity and be associated with increased adverse effects resulting in early

  11. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes

    PubMed Central

    Edagwa, Benson J.; Guo, Dongwei; Puligujja, Pavan; Chen, Han; McMillan, JoEllyn; Liu, Xinming; Gendelman, Howard E.; Narayanasamy, Prabagaran

    2014-01-01

    Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl-INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 μg/106 cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 μg/106 cells for native drugs. High RIF and INHP levels were retained in MDM for >15 d following nanoparticle loading. Rapid loss of native drugs was observed in cells and culture fluids within 24 h. Antimicrobial activities were determined against Mycobacterium smegmatis (M. smegmatis). Coadministration of nanoformulated RIF and INHP provided a 6-fold increase in therapeutic efficacy compared with equivalent concentrations of native drugs. Notably, nanoformulated RIF and INHP were found to be localized in recycling and late MDM endosomal compartments. These were the same compartments that contained the pathogen. Our results demonstrate the potential of antimicrobial nanomedicines to simplify MTB drug regimens.—Edagwa, B. J., Guo, D., Puligujja, P., Chen, H., McMillan, J., Liu, X., Gendelman, H. E., Narayanasamy, P. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes. PMID:25122556

  12. Depletion of praziquantel in plasma and muscle tissue of cultured rockfish Sebastes schlegeli after oral and bath treatment.

    PubMed

    Kim, K H; Kim, C S; Kim, J W

    2001-08-01

    Depletion of praziquantel in plasma and muscle tissue after oral and bath treatments was studied in cultured rockfish Sebastes schlegeli. In the oral treatment, a single dose of 400 mg praziquantel kg(-1) body weight was administered by intubation of the stomach. A bath treatment at 100 ppm of praziquantel for 4 min was also carried out. Plasma and muscle tissue samples were collected at 3, 6, 12, 24, 48, 72, 96, 120, 144 and 168 h post-treatment, and analyzed for praziquantel by reversed-phase HPLC using diazepam as the internal standard. Following oral treatment, praziquantel was detected in plasma and muscle tissue until 96 h after treatment. In plasma the praziquantel concentration was highest at the 9 h sampling time and declined sharply at the 48 h sampling point. The concentrations of praziquantel in the muscle tissue were lower than those in the plasma, and the highest value was found at the 9 h sampling time. Following bath treatment, praziquantel was found in plasma and muscle tissue until 72 and 24 h after treatment, respectively. In plasma the praziquantel concentration was highest at the 12 h sampling time and declined sharply thereafter. The concentrations of praziquantel in the muscle tissue were significantly lower than those in the plasma, and the concentrations declined consistently with time. PMID:11558729

  13. Effect of Dissection and Reconstruction of Palatal Muscles on Morphological Features and Ultrastructure of the Oral Musculature in Cats

    PubMed Central

    Han, Wei; Wang, Zhiyong; Qi, Xiaofeng; Shen, Hao

    2016-01-01

    The study was designed to determine the effect of dissection and reconstruction of palatal muscles on muscle morphology in cats. 27 cats were randomly divided into three groups according to the extent of muscle dissection from the palatal midline. All dissections were performed from the posterior border of the hard palate, and the muscles were allowed to reconstruct over time. The morphological features were determined by hematoxylin and eosin staining of tissue sections, and ultrastructure was observed under a transmission electron microscope. As a result, no obvious differences were evident in the morphological features or ultrastructure of animals in the <1/3rd and 1/3rd-2/3rd area groups. In the >2/3rd area group, the muscles fibers were disordered and inflammatory cell infiltration and naïve muscle cells were found at one month after surgery. At the second and third month after surgery, the muscle fibers showed regular alignment, the naïve muscle fibers gradually matured, and the number of infiltrating inflammatory cells decreased. Muscle ultrastructure analysis revealed that myocommata were correctly aligned, and the Z line was more distinct. In conclusion, extensive dissection of palatal muscles does not result in fibrosis. Injury to oral musculature can be repaired and the musculature regenerated over time.

  14. Effect of Dissection and Reconstruction of Palatal Muscles on Morphological Features and Ultrastructure of the Oral Musculature in Cats

    PubMed Central

    Han, Wei; Wang, Zhiyong; Qi, Xiaofeng; Shen, Hao

    2016-01-01

    The study was designed to determine the effect of dissection and reconstruction of palatal muscles on muscle morphology in cats. 27 cats were randomly divided into three groups according to the extent of muscle dissection from the palatal midline. All dissections were performed from the posterior border of the hard palate, and the muscles were allowed to reconstruct over time. The morphological features were determined by hematoxylin and eosin staining of tissue sections, and ultrastructure was observed under a transmission electron microscope. As a result, no obvious differences were evident in the morphological features or ultrastructure of animals in the <1/3rd and 1/3rd-2/3rd area groups. In the >2/3rd area group, the muscles fibers were disordered and inflammatory cell infiltration and naïve muscle cells were found at one month after surgery. At the second and third month after surgery, the muscle fibers showed regular alignment, the naïve muscle fibers gradually matured, and the number of infiltrating inflammatory cells decreased. Muscle ultrastructure analysis revealed that myocommata were correctly aligned, and the Z line was more distinct. In conclusion, extensive dissection of palatal muscles does not result in fibrosis. Injury to oral musculature can be repaired and the musculature regenerated over time. PMID:27699171

  15. Long-acting injectables and risk for rehospitalization among patients with schizophrenia in the home care program in Taiwan.

    PubMed

    Ju, Po-Chung; Chou, Frank Huang-Chih; Lai, Te-Jen; Chuang, Po-Ya; Lin, Yung-Jung; Yang, Ching-Wen Wendy; Tang, Chao-Hsiun

    2014-02-01

    We aimed at evaluating the relationship between medication and treatment effectiveness in a home care setting among patients with schizophrenia. Patients with schizophrenia hospitalized between 2004 and 2009 with a primary International Classification of Diseases, Ninth Revision, Clinical Modification code of 295 were identified from Psychiatric Inpatient Medical Claims Data released by the National Health Research Institute in Taiwan. Patients who joined the home care program after discharge and were prescribed long-acting injection (LAI) (the LAI group) or oral antipsychotic medications (the oral group) were included as study subjects. The final sample for the study included 810 participants in the LAI group and 945 in the oral group. Logistic regression was performed to examine the independent effect of LAI medication on the risk for rehospitalization within the 12-month observation window after controlling for patient and hospital characteristics and propensity score quintile adjustment. The unadjusted odds ratio for rehospitalization risk was 0.80 (confidence interval, 0.65-0.98) for the LAI group compared to the oral group. The adjusted odds ratio was further reduced to 0.78 (confidence interval, 0.63-0.97). Results remained unchanged when the propensity score quintiles were entered into the regression for further adjustment. In a home care setting, patients treated with long-acting antipsychotic agents are at a significantly lower risk for psychiatric rehospitalization than those treated with oral medication. Consequently, LAI home-based treatment for the prevention of schizophrenia relapse may lead to substantial clinical and economic benefits. PMID:24145217

  16. Long-acting injectables and risk for rehospitalization among patients with schizophrenia in the home care program in Taiwan.

    PubMed

    Ju, Po-Chung; Chou, Frank Huang-Chih; Lai, Te-Jen; Chuang, Po-Ya; Lin, Yung-Jung; Yang, Ching-Wen Wendy; Tang, Chao-Hsiun

    2014-02-01

    We aimed at evaluating the relationship between medication and treatment effectiveness in a home care setting among patients with schizophrenia. Patients with schizophrenia hospitalized between 2004 and 2009 with a primary International Classification of Diseases, Ninth Revision, Clinical Modification code of 295 were identified from Psychiatric Inpatient Medical Claims Data released by the National Health Research Institute in Taiwan. Patients who joined the home care program after discharge and were prescribed long-acting injection (LAI) (the LAI group) or oral antipsychotic medications (the oral group) were included as study subjects. The final sample for the study included 810 participants in the LAI group and 945 in the oral group. Logistic regression was performed to examine the independent effect of LAI medication on the risk for rehospitalization within the 12-month observation window after controlling for patient and hospital characteristics and propensity score quintile adjustment. The unadjusted odds ratio for rehospitalization risk was 0.80 (confidence interval, 0.65-0.98) for the LAI group compared to the oral group. The adjusted odds ratio was further reduced to 0.78 (confidence interval, 0.63-0.97). Results remained unchanged when the propensity score quintiles were entered into the regression for further adjustment. In a home care setting, patients treated with long-acting antipsychotic agents are at a significantly lower risk for psychiatric rehospitalization than those treated with oral medication. Consequently, LAI home-based treatment for the prevention of schizophrenia relapse may lead to substantial clinical and economic benefits.

  17. Oral hydroxycitrate supplementation enhances glycogen synthesis in exercised human skeletal muscle.

    PubMed

    Cheng, I-Shiung; Huang, Shih-Wei; Lu, Hsang-Chu; Wu, Ching-Lin; Chu, Ying-Chieh; Lee, Shin-Da; Huang, Chih-Yang; Kuo, Chia-Hua

    2012-04-01

    Glycogen stored in skeletal muscle is the main fuel for endurance exercise. The present study examined the effects of oral hydroxycitrate (HCA) supplementation on post-meal glycogen synthesis in exercised human skeletal muscle. Eight healthy male volunteers (aged 22·0 (se 0·3) years) completed a 60-min cycling exercise at 70-75 % VO₂max and received HCA or placebo in a crossover design repeated after a 7 d washout period. They consumed 500 mg HCA or placebo with a high-carbohydrate meal (2 g carbohydrate/kg body weight, 80 % carbohydrate, 8 % fat, 12 % protein) for a 3-h post-exercise recovery. Muscle biopsy samples were obtained from vastus lateralis immediately and 3 h after the exercise. We found that HCA supplementation significantly lowered post-meal insulin response with similar glucose level compared to placebo. The rate of glycogen synthesis with the HCA meal was approximately onefold higher than that with the placebo meal. In contrast, GLUT4 protein level after HCA supplementation was significantly decreased below the placebo level, whereas expression of fatty acid translocase (FAT)/CD36 mRNA was significantly increased above the placebo level. Furthermore, HCA supplementation significantly increased energy reliance on fat oxidation, estimated by the gaseous exchange method. However, no differences were found in circulating NEFA and glycerol levels with the HCA meal compared with the placebo meal. The present study reports the first evidence that HCA supplementation enhanced glycogen synthesis rate in exercised human skeletal muscle and improved post-meal insulin sensitivity. PMID:21824444

  18. Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.

    PubMed

    Citrome, Leslie

    2016-01-01

    Aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL) are two different long-acting injectable formulations of aripiprazole. AM 400 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial, as well as in a double-blind, placebo-controlled, randomized-withdrawal maintenance study, and in two non-inferiority maintenance studies. AL is a prodrug of aripiprazole and available in 441 mg, 662 mg or 882 mg strengths. AL 441 mg and 882 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial. The pharmacokinetic profile of AL also led to approval of dosing intervals of every 6 weeks for the 882 mg dose. The overall tolerability profiles of both products are consistent with what is known about oral aripiprazole.

  19. Physiologically-Based Pharmacokinetic Modelling to Inform Development of Intramuscular Long Acting Nanoformulations for HIV

    PubMed Central

    Rajoli, Rajith KR; Back, David J; Rannard, Steve; Meyers, Caren Freel; Flexner, Charles; Owen, Andrew; Siccardi, Marco

    2014-01-01

    Background and Objectives Antiretrovirals (ARVs) are currently used for the treatment and prevention of HIV infection. Poor adherence and low tolerability of some existing oral formulations can hinder their efficacy. Long-acting (LA) injectable nanoformulations could help address these complications by simplifying ARV administration. The aim of this study is to inform the optimisation of intramuscular LA formulations for eight ARVs through physiologically-based pharmacokinetic (PBPK) modelling. Methods A whole-body PBPK model was constructed using mathematical descriptions of molecular, physiological and anatomical processes defining pharmacokinetics. These models were validated against available clinical data and subsequently used to predict the pharmacokinetics of injectable LA formulations Results The predictions suggest that monthly intramuscular injections are possible for dolutegravir, efavirenz, emtricitabine, raltegravir, rilpivirine and tenofovir provided that technological challenges to control release rate can be addressed. Conclusions These data may help inform the target product profiles for LA ARV reformulation strategies. PMID:25523214

  20. Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

    PubMed Central

    Montemagni, Cristiana; Frieri, Tiziana; Rocca, Paola

    2016-01-01

    Long-acting injectable antipsychotics (LAIs) were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs) combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL). Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other SGA-LAIs are still lacking. Lastly, some data on their use, especially in first-episode or recent-onset schizophrenia and in refractory or treatment-resistant schizophrenia, is available. PMID:27143893

  1. Serum ghrelin levels in acromegaly: effects of surgical and long-acting octreotide therapy.

    PubMed

    Freda, Pamela U; Reyes, Carlos M; Conwell, Irene M; Sundeen, Robert E; Wardlaw, Sharon L

    2003-05-01

    The orexigenic peptide, ghrelin, is regulated by acute and chronic nutritional state. Although exogenously administered ghrelin stimulates pituitary GH secretion, little is known about the role of ghrelin in endogenous GH secretion or how high GH and IGF-I levels in acromegaly could affect ghrelin secretion and vice versa. Therefore, we evaluated fasting and post oral glucose tolerance test serum ghrelin levels in 19 patients with active acromegaly at baseline and after either surgery in 9 of these or administration of long-acting octreotide (Sandostatin LAR) in the other 10 patients. After surgical cure, fasting ghrelin rose from 312 +/- 56 pg/ml to 548 +/- 97 pg/ml (P = 0.013). Fasting serum ghrelin levels were higher in all patients after surgery and ranged between 112% and 349% of presurgery levels. Ghrelin levels fell significantly during long-acting octreotide therapy from 447 +/- 34 pg/ml to 206 +/- 15 pg/ml (P < 0.0001); ghrelin levels on octreotide ranged between 26% and 70% of baseline levels. Serum ghrelin levels were suppressed significantly during the oral glucose tolerance test in both groups. Pretherapy ghrelin levels correlated negatively with serum insulin levels (r = -0.494; P = 0.03) and insulin resistance as estimated by the homeostasis model assessment score (r = -0.573; P = 0.01). In patients without diabetes mellitus, serum insulin levels in the surgical group were 19.7 +/- 5.4 microU/ml before surgery and fell to 9.7 +/- 0.93 microU/ml after surgery (P = 0.05); levels in the octreotide group were 13.9 +/- 2.8 microU/ml before and fell to 11.2 +/- 2.8 microU/ml on octreotide (P = 0.03). Pretherapy ghrelin levels did not correlate with weight or body mass index, but after therapy in the surgery group ghrelin correlated negatively with weight (r = -0.823, P = 0.012) as has been demonstrated by others in healthy subjects. Ghrelin secretion is dysregulated in active acromegaly; lowered serum levels of ghrelin in active acromegaly rise along with

  2. [Indications and medical survey of long acting progestatives used for contraception (author's transl)].

    PubMed

    Molitor-peffer, M P

    1982-10-01

    About 600 injections per year are administered in a Luxembourg family planning center using 3 types of long acting progestatives: Depo Provera 150 and 450 and Norigest. The method is no longer reserved for women with completed families and the mentally handicapped since its reversibility has been proven. Patients seeking this type of contraception must meet the same criteria as for oral contraceptives except that women with contraindications for estrogens may tolerate progestatives. Long acting progestatives offer the safety of minipills along with high effectiveness since the risk of forgetting a pill is removed. Some women with cardiac disease, diabetes, and circulatory problems are able to use injectables, but caution should be exercised with hypertensives and the obese because of possible weight gain. Women with coagulation problems or suspected fibromas should be excluded. Administered postpartum, pure progestatives do not affect lactation. Menstrual cycles are completely disturbed, with irregular and unpredictable bleeding until amenorrhea appears after 3-6 months. Women who are psychologically unable to accept amenorrhea should not use this method, as they are more likely to experience undesirable side effects. Return of fertility upon termination of use poses no problem and usually occurs after 6-10 months, even after a single injection. Treatment with a sequential contraceptive beginning on the day when the next injection would have been given may help to reestablish menstruation. The physician should determine through a preliminary interview the couple's psychological readiness for this type of contraception. A careful medical history and gynecological examination should be done to rule out contraindications, and treatment should begin in the 1st 3 days of the cycle. Irregular and prolonged bleeding after 6 months of use can be treated with oral administration of estrogen, or by proceeding to the next injection ahead of schedule. Administration of a mild

  3. Thienorphine is a potent long-acting partial opioid agonist: a comparative study with buprenorphine.

    PubMed

    Yu, Gang; Yue, Yong-Juan; Cui, Meng-Xun; Gong, Ze-Hui

    2006-07-01

    A strategy in the development of new treatment for opioid addiction is to find partial opioid agonists with properties of long duration of action and high oral bioavailability. In a search for such compounds, thienorphine, a novel analog of buprenorphine, was synthesized. Here, we reported that, like buprenorphine, thienorphine bound potently and nonselectively to mu-, delta-, and kappa-opioid receptors stably expressed in CHO (Chinese hamster ovary) cells and behaved as a partial agonist at mu-opioid receptor. However, some differences were observed between the pharmacological profiles of thienorphine and buprenorphine. In vitro, thienorphine was more potent than buprenorphine in inhibiting [3H]diprenorphine and stimulating guanosine 5'-O-(3-[35S]thio)triphosphate binding to rat mu-opioid receptor stably expressed in CHO cells. In vivo, thienorphine exhibited a less potent but more efficacious antinociceptive effect with an ED50 value of 0.25 mg/kg s.c. and more potent antimorphine effect with an ED50 value of 0.64 mg/kg intragastric, compared with buprenorphine. Additionally, the bioavailability of thienorphine was greatly higher than that of buprenorphine after oral administration. Moreover, compared with buprenorphine, thienorphine showed a similar long-lasting antinociceptive effect but a much longer antagonism of morphine-induced lethality (more than 15 days). These results indicate that thienorphine is a potent, long-acting partial opioid agonist with high oral bioavailability and may have possible application in treating addiction. PMID:16569757

  4. Physician and patient benefit–risk preferences from two randomized long-acting injectable antipsychotic trials

    PubMed Central

    Katz, Eva G; Hauber, Brett; Gopal, Srihari; Fairchild, Angie; Pugh, Amy; Weinstein, Rachel B; Levitan, Bennett S

    2016-01-01

    Purpose To quantify clinical trial participants’ and investigators’ judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence. Methods Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI) antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models. Results Patients (N=214) and physicians (N=438) preferred complete improvement in positive symptoms (severe to none) as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P<0.05), irrespective of prior adherence to oral antipsychotic treatment, with physicians showing greater preference for a 3-month over a 1-month LAI for nonadherent patients. Physicians were willing to accept treatments with reduced efficacy for patients with prior poor adherence. The maximum decrease in efficacy (95% confidence interval [CI]) that physicians would accept for switching a patient from daily oral to 3-month injectable was as follows: adherent: 9.8% (95% CI: 7.2–12.4), 20% nonadherent: 25.4% (95% CI: 21.0–29.9), and 50% nonadherent: >30%. For patients, adherent: 10.1% (95% CI: 6.1–14.1), nonadherent: the change in efficacy studied was regarded as unimportant. Conclusion Improvement in positive symptoms was the most important attribute. Patients and physicians preferred LAIs over oral antipsychotics, with physicians showing a greater preference for 3-month over 1-month LAI. Physicians and patients were willing to accept reduced efficacy in exchange for switching a patient from

  5. Long-Acting Beta Agonists Enhance Allergic Airway Disease

    PubMed Central

    Knight, John M.; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O.; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A.; Milner, Joshua D.; Zhang, Yuan; Mandal, Pijus K.; Luong, Amber; Kheradmand, Farrah

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  6. Pharmacokinetics of Injectable, Long-Acting Nevirapine for HIV Prophylaxis in Breastfeeding Infants

    PubMed Central

    Cortez, John M.; Quintero, Rafaela; Moss, John A.; Beliveau, Martin; Smith, Thomas J.

    2014-01-01

    Mother-to-child transmission (MTCT) of HIV-1 remains a global health problem. The World Health Organization (WHO) recommendations advise the administration of a once-daily, oral, prophylactic regimen of the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) from birth until 4 to 6 weeks of age for infants born to HIV-infected mothers in regions without access to safe and nutritionally adequate alternatives to breast milk. A critical factor driving the successful implementation of the WHO guidelines involves sustaining high adherence to the frequent dosing. With these challenges in mind, we have developed the first injectable, sustained-release NVP formulations with the goal of providing, for 6 weeks or longer, preventative plasma drug levels from a single subcutaneous administration at birth. The long-acting NVP consists of large (>50 μm), monodisperse NVP particles coated with biocompatible polymers that control the drug release kinetics. Two lead formulations exhibiting burst-free, sustained-release kinetics for up to 75 days in vitro were developed. Subsequent in vivo studies in rats demonstrated no toxicity related to the formulations. Rat plasma NVP concentrations were above the analytical assay's limit of quantification for up to 28 days. Pharmacokinetic analysis of the rat plasma NVP concentration-time data allowed absorption rate constants to be calculated. These data then were used to simulate infant NVP exposure from a single injected dose (<200 mg) of our long-acting formulations, demonstrating preliminary feasibility of the technology to maintain safe, preventative NVP plasma levels (0.2 to 3.0 μg ml−1) for 6 weeks or longer. PMID:25313219

  7. Planning ahead for implementation of long acting HIV prevention: challenges and opportunities

    PubMed Central

    Meyers, Kathrine

    2015-01-01

    Purpose of Review Broad-based access, uptake, and dissemination of daily oral HIV pre-exposure prophylaxis (PrEP) have been slow, despite strong evidence for efficacy. Effective and efficient implementation of long-acting (LA) HIV prevention products will require both analysis of the dynamics and determinants of daily oral PrEP implementation and identification of the distinct challenges and opportunities inherent in emerging technologies. Recent Findings Evidence suggests the importance of addressing implementation issues at three levels: patient, provider, and system. Patient-level factors include targeted education and messaging, tailored supports to enhance acceptability and uptake, and effective strategies for promoting adherence/persistence and retention in care. Provider-level factors include engaging a broad mix of providers, while ensuring adequate training and support for patient assessment, counseling, and follow-up. Systems-level factors include optimal delivery modalities, resource allocation, and ensuring access to populations most in need of new prevention options. Summary Formative social/behavioral research must be undertaken proactively in order to prepare for and address future implementation challenges and reduce the gap between proving efficacy in clinical trials and assuring real-world effectiveness. Conceptualizing new HIV prevention technologies as behavioral interventions at the level of the patient, provider, and system will be paramount to effective and efficient implementation. PMID:26049956

  8. Worsening of myasthenia gravis after administration of injectable long-acting risperidone for treatment of schizophrenia; first case report and a call for caution.

    PubMed

    Al-Hashel, Jasem Y; Ismail, Ismail Ibrahim; John, John K; Ibrahim, Mohammed; Ali, Mahmoud

    2016-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to autoantibodies affecting the neuromuscular junction. Co-occurrence of myasthenia gravis and schizophrenia is very rare and raises a challenge in management of both diseases. Antipsychotic drugs exhibit anticholinergic side effects and have the potentials of worsening myasthenia. Long-acting risperidone is an injectable atypical antipsychotic drug that has not been previously reported to worsen myasthenia gravis in literature. We report the first case report of worsening of myasthenia after receiving long-acting risperidone injection for schizophrenia in a 29-year-old female with both diseases. She started to have worsening 2 weeks following the first injection and her symptoms persisted despite receiving plasma exchange. This could be explained by the pharmacokinetics of the drug. We recommend that long-acting risperidone should be used with caution in patients with myasthenia gravis, and clinicians must be aware of the potential risks of this therapy. PMID:27012182

  9. Worsening of myasthenia gravis after administration of injectable long-acting risperidone for treatment of schizophrenia; first case report and a call for caution.

    PubMed

    Al-Hashel, Jasem Y; Ismail, Ismail Ibrahim; John, John K; Ibrahim, Mohammed; Ali, Mahmoud

    2016-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to autoantibodies affecting the neuromuscular junction. Co-occurrence of myasthenia gravis and schizophrenia is very rare and raises a challenge in management of both diseases. Antipsychotic drugs exhibit anticholinergic side effects and have the potentials of worsening myasthenia. Long-acting risperidone is an injectable atypical antipsychotic drug that has not been previously reported to worsen myasthenia gravis in literature. We report the first case report of worsening of myasthenia after receiving long-acting risperidone injection for schizophrenia in a 29-year-old female with both diseases. She started to have worsening 2 weeks following the first injection and her symptoms persisted despite receiving plasma exchange. This could be explained by the pharmacokinetics of the drug. We recommend that long-acting risperidone should be used with caution in patients with myasthenia gravis, and clinicians must be aware of the potential risks of this therapy.

  10. Effects of Discontinuation of Paliperidone Long-Acting Injectable After Switching from Risperidone Long-Acting Injectable Switching

    PubMed Central

    Watanabe, Takafumi; Yamada, Atsurou

    2016-01-01

    Background Risperidone long-acting injection (RLAI) is increasingly being switched to paliperidone palmitate (PP) because of several benefits. However, this switching is not always successful. Methods We examined patient profiles following discontinuation of PP after switching from RLAI. We collected the electronic records of 24 patients with schizophrenia who had switched from RLAI to PP treatment at our hospital between November 2013 and March 2014. Twelve patients continued PP injection for over 1 year (PP-continuers), the other 12 patients discontinued within 1 year (PP-discontinuers), and both groups were followed up until December 31, 2014. Results PP-discontinuers had significantly shorter RLAI-administration period (mean 73.1 ± 59.0 weeks versus 148.5 ± 75.0 weeks), and lower chlorpromazine (CP) equivalent mean doses (mean 553.5 ± 251.0 mg versus 1002.5 ± 529.3 mg) compared with PP-continuers. The CP equivalent mean dose of PP-discontinuers had increased at the time of discontinuation and their social status became significantly worse. Six PP-discontinuers (50%) re-switched to RLAI, and their social status was not significantly worse at the end of the observation period. Conclusions On switching from RLAI to PP, we need to consider that some patients have had a shorter RLAI-administration period and may require lower amounts of antipsychotics. PMID:27738379

  11. Oral contraceptive use, muscle sympathetic nerve activity, and systemic hemodynamics in young women

    PubMed Central

    Harvey, Ronee E.; Hart, Emma C.; Charkoudian, Nisha; Curry, Timothy B.; Carter, Jason R.; Fu, Qi; Minson, Christopher T.; Joyner, Michael J.; Barnes, Jill N.

    2015-01-01

    Endogenous female sex hormones influence muscle sympathetic nerve activity (MSNA), a regulator of arterial blood pressure and important factor in hypertension development. While nearly 80% of American women report using hormonal contraceptives sometime during their life, the influence of combined oral contraceptives (OCs) on MSNA and systemic hemodynamics remains equivocal. The goal of this study was to determine if women taking OCs have altered MSNA and hemodynamics (cardiac output and total peripheral resistance) at rest during the placebo phase of OC use compared to women with natural menstrual cycles during the early follicular phase. We retrospectively analyzed data from studies in which healthy, premenopausal women (ages 18–35 years old) participated. We collected MSNA values at rest and hemodynamic measurements in women taking OCs (n=53, 25±4 yr) and women with natural menstrual cycles (n=74, 25±4 yr). Blood pressure was higher in women taking OCs versus those with natural menstrual cycles (mean arterial pressure: 89±1 vs. 85±1 mmHg, respectively; p=0.01), although MSNA was similar in both groups (MSNA burst incidence: 16±1 vs. 18±1 bursts/100 heartbeats, respectively, p=0.19). In a subset of women in which detailed hemodynamic data were available, those taking OCs (n=33) had similar cardiac output (4.9±0.2 vs. 4.7±0.2 L/min, respectively; p=0.47) and total peripheral resistance (19.2±0.8 vs. 20.0±0.9 units, respectively; p=0.51) as women with natural menstrual cycles (n=22). In conclusion, women taking OCs have higher resting blood pressure and similar MSNA and hemodynamics during the placebo phase of OC use compared to naturally menstruating women in the early follicular phase. PMID:26101348

  12. Oral Contraceptive Use, Muscle Sympathetic Nerve Activity, and Systemic Hemodynamics in Young Women.

    PubMed

    Harvey, Ronee E; Hart, Emma C; Charkoudian, Nisha; Curry, Timothy B; Carter, Jason R; Fu, Qi; Minson, Christopher T; Joyner, Michael J; Barnes, Jill N

    2015-09-01

    Endogenous female sex hormones influence muscle sympathetic nerve activity (MSNA), a regulator of arterial blood pressure and important factor in hypertension development. Although ≈80% of American women report using hormonal contraceptives sometime during their life, the influence of combined oral contraceptives (OCs) on MSNA and systemic hemodynamics remains equivocal. The goal of this study was to determine whether women taking OCs have altered MSNA and hemodynamics (cardiac output and total peripheral resistance) at rest during the placebo phase of OC use compared with women with natural menstrual cycles during the early follicular phase. We retrospectively analyzed data from studies in which healthy, premenopausal women (aged 18-35 years) participated. We collected MSNA values at rest and hemodynamic measurements in women taking OCs (n=53; 25±4 years) and women with natural menstrual cycles (n=74; 25±4 years). Blood pressure was higher in women taking OCs versus those with natural menstrual cycles (mean arterial pressure, 89±1 versus 85±1 mm Hg, respectively; P=0.01), although MSNA was similar in both groups (MSNA burst incidence, 16±1 versus 18±1 bursts/100 heartbeats, respectively; P=0.19). In a subset of women in which detailed hemodynamic data were available, those taking OCs (n=33) had similar cardiac output (4.9±0.2 versus 4.7±0.2 L/min, respectively; P=0.47) and total peripheral resistance (19.2±0.8 versus 20.0±0.9 U, respectively; P=0.51) as women with natural menstrual cycles (n=22). In conclusion, women taking OCs have higher resting blood pressure and similar MSNA and hemodynamics during the placebo phase of OC use when compared with naturally menstruating women in the early follicular phase. PMID:26101348

  13. Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease

    PubMed Central

    Karner, Charlotta; Cates, Christopher J

    2014-01-01

    Background Long-acting bronchodilators comprising long-acting beta2-agonists and the anticholinergic agent tiotropium are commonly used for managing persistent symptoms of chronic obstructive pulmonary disease. Combining these treatments, which have different mechanisms of action, may be more effective than the individual components. However, the benefits and risks of combining tiotropium and long-acting beta2-agonists for the treatment of chronic obstructive pulmonary (COPD) disease are unclear. Objectives To assess the relative effects of treatment with tiotropium in addition to long-acting beta2-agonist compared to tiotropium or long-acting beta2-agonist alone in patients with chronic obstructive pulmonary disease. Search methods We searched the Cochrane Airways Group Specialised Register of trials and clinicaltrials.gov up to January 2012. Selection criteria We included parallel group, randomised controlled trials of three months or longer comparing treatment with tiotropium in addition to long-acting beta2-agonist against tiotropium or long-acting beta2-agonist alone for patients with chronic obstructive pulmonary disease. Data collection and analysis Two review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials. Main results Five trials were included in this review, mostly recruiting participants with moderate or severe chronic obstructive pulmonary disease. All of them compared tiotropium in addition to long-acting beta2-agonist to tiotropium alone, but only one trial additionally compared a combination of the two types of bronchodilator with long-acting beta2-agonist (formoterol) alone. Two studies used the long-acting beta2-agonist indacaterol, two used formoterol and one used salmeterol. Compared to tiotropium alone (3263 patients), treatment with tiotropium plus long-acting

  14. Electromyographic analysis of trapezius and sternocleidomastoideus muscles during nasal and oral inspiration in nasal- and mouth-breathing children.

    PubMed

    Ribeiro, E C; Marchiori, S C; Silva, A M T

    2002-08-01

    The purpose of this study was to evaluate sternocleidomastoideus (SCM) and trapezius (superior fibers) muscle activity patterns in mouth-breathing children, and to compare them with nasal-breathing children. Forty-six children, of both sexes, ranging from 8 to 12 years old, were evaluated through electromyography. The selected children were divided into two groups; Group I, was made up of 26 mouth-breathing children and Group II of 20 nasal-breathing children. Electromyographic recordings were obtained through surface electrodes in the SCM and trapezius muscles, bilaterally, during oral and nasal inspiration. Root-mean-square (RMS) data expressed in microvolts (microV), were analyzed using the Kruskall-Wallis statistical test. From the results obtained, we concluded that there was a significant difference in the muscle activity between the groups, with higher activity during nasal inspiration in the mouth-breathing group. During oral inspiration, there was no significant difference between groups. Within the groups, only the mouth-breathing group showed higher activity during nasal inspiration.

  15. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  16. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  17. A 7-day oral supplementation with branched-chain amino acids was ineffective to prevent muscle damage during a marathon.

    PubMed

    Areces, Francisco; Salinero, Juan Jose; Abian-Vicen, Javier; González-Millán, Cristina; Gallo-Salazar, Cesar; Ruiz-Vicente, Diana; Lara, Beatriz; Del Coso, Juan

    2014-05-01

    The aim of this study was to determine the effectiveness of a 7-day oral supplementation with branched-chain amino acids (BCAA) to prevent muscle damage during a marathon. Forty-six experienced runners were randomly divided into two groups, one with BCAA supplementation (n = 25, supplemented with 5 g day(-1) of powdered 1:0.5:0.5 leucine:isoleucine:valine, during the 7 days prior to the competition) and the other as a control group (n = 21, supplemented with an isocaloric placebo). Before the marathon race and within 3 min of finishing, leg muscle power was measured with a maximal countermovement jump and a urine sample was obtained. During the race, running pace was measured by means of a time-chip. Myoglobin concentration was determined in the urine samples as an indirect marker of muscle damage. A visual analog scale (0-10 points) was used to assess leg muscle pain during the race. In the BCAA group, the mean running pace during the marathon was similar to the control group (3.3 ± 0.4 vs. 3.3 ± 0.5 m s(-1), respectively, 0.98). The pre- to post-race reduction in muscle power was similar in both BCAA and control groups (-23.0 ± 16.1 vs. -17.3 ± 13.8 %, P = 0.13). Post-race urine myoglobin concentration was similar in both BCAA and control groups (5.4 ± 7.5 vs. 4.5 ± 8.6 μg mL(-1), P = 0.70). Finally, there were no differences between groups in the perceived muscle pain during the race (6 ± 1 vs. 5 ± 1 points, P = 0.80). A 7-day supplementation of BCAA (5 g day(-1)) did not increase the running performance during a marathon. Furthermore, BCAA supplementation was ineffective to prevent muscle power loss, muscle damage or perceived muscle pain during a marathon race. PMID:24477835

  18. A 7-day oral supplementation with branched-chain amino acids was ineffective to prevent muscle damage during a marathon.

    PubMed

    Areces, Francisco; Salinero, Juan Jose; Abian-Vicen, Javier; González-Millán, Cristina; Gallo-Salazar, Cesar; Ruiz-Vicente, Diana; Lara, Beatriz; Del Coso, Juan

    2014-05-01

    The aim of this study was to determine the effectiveness of a 7-day oral supplementation with branched-chain amino acids (BCAA) to prevent muscle damage during a marathon. Forty-six experienced runners were randomly divided into two groups, one with BCAA supplementation (n = 25, supplemented with 5 g day(-1) of powdered 1:0.5:0.5 leucine:isoleucine:valine, during the 7 days prior to the competition) and the other as a control group (n = 21, supplemented with an isocaloric placebo). Before the marathon race and within 3 min of finishing, leg muscle power was measured with a maximal countermovement jump and a urine sample was obtained. During the race, running pace was measured by means of a time-chip. Myoglobin concentration was determined in the urine samples as an indirect marker of muscle damage. A visual analog scale (0-10 points) was used to assess leg muscle pain during the race. In the BCAA group, the mean running pace during the marathon was similar to the control group (3.3 ± 0.4 vs. 3.3 ± 0.5 m s(-1), respectively, 0.98). The pre- to post-race reduction in muscle power was similar in both BCAA and control groups (-23.0 ± 16.1 vs. -17.3 ± 13.8 %, P = 0.13). Post-race urine myoglobin concentration was similar in both BCAA and control groups (5.4 ± 7.5 vs. 4.5 ± 8.6 μg mL(-1), P = 0.70). Finally, there were no differences between groups in the perceived muscle pain during the race (6 ± 1 vs. 5 ± 1 points, P = 0.80). A 7-day supplementation of BCAA (5 g day(-1)) did not increase the running performance during a marathon. Furthermore, BCAA supplementation was ineffective to prevent muscle power loss, muscle damage or perceived muscle pain during a marathon race.

  19. Combination treatment with risperidone long-acting injection and psychoeducational approaches for preventing relapse in schizophrenia

    PubMed Central

    Zhao, Yueren; Kishi, Taro; Iwata, Nakao; Ikeda, Manabu

    2013-01-01

    A recent meta-analysis showed that long-acting injectable (LAI) antipsychotics were not superior to oral antipsychotics for preventing relapse in patients with schizophrenia. We therefore designed a treatment strategy combining risperidone LAI and COMPASS (COMprehensive Psycho-educational Approach and Scheme Set), an original psychoeducational program supporting treatment with risperidone LAI and evaluating subjective treatment satisfaction, transition of symptoms, and effectiveness in preventing symptomatic relapse. The aim of this study was to examine whether addition of COMPASS to risperidone LAI was more effective in preventing relapse in schizophrenia patients than risperidone LAI alone, with the latter group consisting of patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients were followed up for 6 months, with COMPASS continuously implemented from the transition to the observation phase. The primary efficacy measurements were relapse rate (rates of rehospitalization and discontinuation due to inefficacy). Secondary efficacy measurements were the Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Functioning (GAF) scores. Of the 96 patients originally enrolled, 19 (19.8%) were discontinued from all causes. During the 6-month study period, ten of the 96 patients (10.4%) relapsed, compared with a 12.2% relapse rate in patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients showed significant improvements in BPRS total scores (P = 0.0031), BPRS positive (P = 0.0451), BRPS negative (P < 0.0001), and general subscale scores (P = 0.0031), and GAF (P < 0.0001) from baseline to 6 months. In conclusion, the lower relapse rate observed in patients treated with COMPASS plus risperidone LAI than in patients treated with risperidone LAI alone suggests that COMPASS may have benefits in the treatment of schizophrenia, indicating a need for randomized, controlled trials in larger numbers of patients. PMID:24194642

  20. Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs

    PubMed Central

    2012-01-01

    Based on its PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its SC injection to dogs (≤ 0.3 mL per injection site), and results compared with the oral (PO) and IV pharmacokinetics of DOX-h, prepared as tablet or as freshly made solution. A crossover (4 x 4 x 4) study design was employed with 12 Mongrel dogs, with washout periods of 21 days, and at dose of 10 mg/kg in all cases. DOX-h-LA showed the greatest values for bioavailability (199.48%); maximum serum concentration (Cmax) value was 2.8 ± 0.3 with a time to reach Cmax (Tmax) of 2.11 ± 0.12 h and an elimination half-life of 133.61 ± 6.32 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose-interval of at least 1 week h can be achieved for DOX-h-LA, and only 48 h and 24 h after the IV or PO administration of DOX-h as a solution or as tablets, respectively. A non-painful small bulge, apparently non-inflammatory could be distinguished at injection sites. These lumps dissipated completely in 30 days in all cases. PMID:22682068

  1. Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis

    PubMed Central

    Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S.; Fanter, Rob; Yang, Flora; Marzinke, Mark A.; Hendrix, Craig W.; Beliveau, Martin; Moss, John A.; Smith, Thomas J.

    2015-01-01

    Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day−1 in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml−1; interquartile range [IQR], 0.60 to 1.50 ng ml−1) and tenofovir (TFV; median, 15.0 ng ml−1; IQR, 8.8 to 23.3 ng ml−1), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/106 cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations. PMID:25896688

  2. Recent advances in COPD disease management with fixed-dose long-acting combination therapies.

    PubMed

    Bateman, Eric D; Mahler, Donald A; Vogelmeier, Claus F; Wedzicha, Jadwiga A; Patalano, Francesco; Banerji, Donald

    2014-06-01

    Combinations of two long-acting bronchodilators and long-acting bronchodilators with inhaled corticosteroids (ICS) are recommended therapies in the management of chronic obstructive pulmonary disease (COPD). Three fixed-dose combination products have recently been approved for the treatment of COPD (the long-acting β2-agonist plus long-acting muscarinic antagonist [LABA/LAMA] combinations glycopyrronium/indacaterol [QVA149] and umeclidinium/vilanterol, and the LABA/ICS fluticasone furoate/vilanterol), with others currently in late-stage development. LABA/LAMA and LABA/ICS combination therapies demonstrate positive effects on both lung function and patient-reported outcomes, with significant improvements observed with LABA/LAMA combinations compared with placebo, each component alone and other comparators in current use. No new safety concerns have been observed with combinations of long-acting bronchodilators. Combinations of two long-acting bronchodilators represent a new and convenient treatment option in COPD. This review summarizes published efficacy and safety data from clinical trials of both LABA/LAMA and novel LABA/ICS combinations in patients with COPD.

  3. Regulation of skeletal muscle protein degradation and synthesis by oral administration of lysine in rats.

    PubMed

    Sato, Tomonori; Ito, Yoshiaki; Nagasawa, Takashi

    2013-01-01

    Several catabolic diseases and unloading induce muscle mass wasting, which causes severe pathological progression in various diseases and aging. Leucine is known to attenuate muscle loss via stimulation of protein synthesis and suppression of protein degradation in skeletal muscle. The aim of this study was to investigate the effects of lysine intake on protein degradation and synthesis in skeletal muscle. Fasted rats were administered 22.8-570 mg Lys/100 g body weight and the rates of myofibrillar protein degradation were assessed for 0-6 h after Lys administration. The rates of myofibrillar protein degradation evaluated by MeHis release from the isolated muscles were markedly suppressed after administration of 114 mg Lys/100 g body weight and of 570 mg Lys/100 g body weight. LC3-II, a marker of the autophagic-lysosomal pathway, tended to decrease (p=0.05, 0.08) after Lys intake (114 mg/100 g body weight). However, expression of ubiquitin ligase E3 atrogin-1 mRNA and levels of ubiquitinated proteins were not suppressed by Lys intake. Phosphorylation levels of mTOR, S6K1 and 4E-BP1 in the gastrocnemius muscle were not altered after Lys intake. These results suggest that Lys is able to suppress myofibrillar protein degradation at least partially through the autophagic-lysosomal pathway, not the ubiquitin-proteasomal pathway, whereas Lys might be unable to stimulate protein synthesis within this time frame. PMID:24418875

  4. Regulation of skeletal muscle protein degradation and synthesis by oral administration of lysine in rats.

    PubMed

    Sato, Tomonori; Ito, Yoshiaki; Nagasawa, Takashi

    2013-01-01

    Several catabolic diseases and unloading induce muscle mass wasting, which causes severe pathological progression in various diseases and aging. Leucine is known to attenuate muscle loss via stimulation of protein synthesis and suppression of protein degradation in skeletal muscle. The aim of this study was to investigate the effects of lysine intake on protein degradation and synthesis in skeletal muscle. Fasted rats were administered 22.8-570 mg Lys/100 g body weight and the rates of myofibrillar protein degradation were assessed for 0-6 h after Lys administration. The rates of myofibrillar protein degradation evaluated by MeHis release from the isolated muscles were markedly suppressed after administration of 114 mg Lys/100 g body weight and of 570 mg Lys/100 g body weight. LC3-II, a marker of the autophagic-lysosomal pathway, tended to decrease (p=0.05, 0.08) after Lys intake (114 mg/100 g body weight). However, expression of ubiquitin ligase E3 atrogin-1 mRNA and levels of ubiquitinated proteins were not suppressed by Lys intake. Phosphorylation levels of mTOR, S6K1 and 4E-BP1 in the gastrocnemius muscle were not altered after Lys intake. These results suggest that Lys is able to suppress myofibrillar protein degradation at least partially through the autophagic-lysosomal pathway, not the ubiquitin-proteasomal pathway, whereas Lys might be unable to stimulate protein synthesis within this time frame.

  5. Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

    PubMed

    Winkelman, L A; Overton, T R

    2013-01-01

    This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows

  6. Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

    PubMed

    Winkelman, L A; Overton, T R

    2013-01-01

    This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows

  7. Free fibula osteocutaneous flap with soleus muscle as a chimeric flap for reconstructing mandibular segmental defect after oral cancer ablation.

    PubMed

    Kuo, Yur-Ren; Shih, Hsiang-Shun; Chen, Chien-Chang; Boca, Radovan; Hsu, Yao-Chung; Su, Chih-Ying; Jeng, Seng-Feng; Wei, Fu-Chan

    2010-06-01

    In some cases, the fibula osteocutaneous flap may not provide sufficient soft tissue for obliterating dead space after tumor ablation. This report describes a modified fibula osteocutaneous flap using a portion of soleus muscle to reduce postoperative complications. This study analyzed 20 patients who underwent ablative oral cancer surgery with mandibular segmental defect between September 2005 and June 2007. Of total, 17 cases were mandible complex defects and 3 were composite defects. Of total, 18 were men and 2 were women, respectively. Age range was 30 to 74 years, and mean age was 53 years. The procedure entailed harvest of chimeric fibula flap with skin paddle and bone segment composed of a sheet of soleus muscle (7 x 4 to 12 x 5 cm in size) originating from the perforator branch of the peroneal artery. The soleus muscle was used to obliterate the dead space of the mouth floor and cheek-neck area. All flaps survived except 1 failure due to venous insufficiency. The submandibular and chin area exhibited mild swelling at the submandibular area early postoperatively. Patients had achieved satisfactory contour without donor site morbidity at a mean 12-months of follow-up. Complications included 2 flaps requiring reoperation due to the flap pedicle compromised. One flap was successfully salvaged but the other failed. Two cases of orocutaneous fistula-induced infection recovered after conservative treatment. Donor site assessment revealed a satisfactory outcome without major donor site morbidity. This refinement in mandibular reconstructive surgery substantially reduces postoperative complications.

  8. Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection

    PubMed Central

    Walensky, Rochelle P.; Jacobsen, Margo M.; Bekker, Linda-Gail; Parker, Robert A.; Wood, Robin; Resch, Stephen C.; Horstman, N. Kaye; Freedberg, Kenneth A.; Paltiel, A. David

    2016-01-01

    Background. For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown. Methods. Using a computer simulation, we compared the following 3 PrEP strategies: no PrEP, standard PrEP (effectiveness, 62%; cost per patient, $150/year), and long-acting PrEP (effectiveness, 75%; cost per patient, $220/year) in South African women at high risk for HIV infection (incidence of HIV infection, 5%/year). We examined the sensitivity of the strategies to changes in key input parameters among several outcome measures, including deaths averted and program cost over a 5-year period; lifetime HIV infection risk, survival rate, and program cost and cost-effectiveness; and budget impact. Results. Compared with no PrEP, standard PrEP and long-acting PrEP cost $580 and $870 more per woman, respectively, and averted 15 and 16 deaths per 1000 women at high risk for infection, respectively, over 5 years. Measured on a lifetime basis, both standard PrEP and long-acting PrEP were cost saving, compared with no PrEP. Compared with standard PrEP, long-acting PrEP was very cost-effective ($150/life-year saved) except under the most pessimistic assumptions. Over 5 years, long-acting PrEP cost $1.6 billion when provided to 50% of eligible women. Conclusions. Currently available standard PrEP is a cost-saving intervention whose delivery should be expanded and optimized. Long-acting PrEP will likely be a very cost-effective improvement over standard PrEP but may require novel financing mechanisms that bring short-term fiscal planning efforts into closer alignment with longer-term societal objectives. PMID:26681778

  9. Comparison of Subjective Experiences and Effectiveness of First-Generation Long-Acting Injectable Antipsychotics and Risperidone Long-Acting Injectables in Patients With Schizophrenia.

    PubMed

    Chen, Wen-Yin; Lin, Shih-Ku

    2016-10-01

    We conducted a cross-sectional study to compare the subjective experiences and clinical effects of first-generation long-acting injectable (FGA-LAI) antipsychotics with those of risperidone long-acting injectables (RIS-LAIs) in 434 schizophrenia patients. Compared with the RIS-LAI group, the patients treated with FGA-LAIs had a significantly longer duration of illness and LAI treatment and were older. Our results suggest that patients treated with FGA-LAI have more satisfactory subjective experiences compared with patients treated with RIS-LAI and that both FGA-LAI and RIS-LAI treatments can prevent relapses and hospitalization. Additional longitudinal studies determining the long-term benefits of RIS-LAI are warranted. PMID:27580495

  10. Can short-term oral fine motor training affect precision of task performance and induce cortical plasticity of the jaw muscles?

    PubMed

    Zhang, Hong; Kumar, Abhishek; Kothari, Mohit; Luo, Xiaoping; Trulsson, Mats; Svensson, Krister G; Svensson, Peter

    2016-07-01

    The aim was to test the hypothesis that short-term oral sensorimotor training of the jaw muscles would increase the precision of task performance and induce neuroplastic changes in the corticomotor pathways, related to the masseter muscle. Fifteen healthy volunteers performed six series with ten trials of an oral sensorimotor task. The task was to manipulate and position a spherical chocolate candy in between the anterior teeth and split it into two equal halves. The precision of the task performance was evaluated by comparing the ratio between the two split halves. A series of "hold-and-split" tasks was also performed before and after the training. The hold force and split force along with the electromyographic (EMG) activity of jaw muscles were recorded. Motor-evoked potentials and cortical motor maps of the right masseter muscle were evoked by transcranial magnetic stimulation. There was a significant effect of series on the precision of the task performance during the short-term oral sensorimotor training (P < 0.002). The hold force during the "hold-and-split" task was significantly lower after training than before the short-term training (P = 0.011). However, there was no change in the split force and the EMG activity of the jaw muscles before and after the training. Further, there was a significant increase in the amplitude of the motor-evoked potentials (P < 0.016) and in the motor cortex map areas (P = 0.033), after the short-term oral sensorimotor training. Therefore, short-term oral sensorimotor task training increased the precision of task performance and induced signs of neuroplastic changes in the corticomotor pathways, related to the masseter muscle.

  11. Can short-term oral fine motor training affect precision of task performance and induce cortical plasticity of the jaw muscles?

    PubMed

    Zhang, Hong; Kumar, Abhishek; Kothari, Mohit; Luo, Xiaoping; Trulsson, Mats; Svensson, Krister G; Svensson, Peter

    2016-07-01

    The aim was to test the hypothesis that short-term oral sensorimotor training of the jaw muscles would increase the precision of task performance and induce neuroplastic changes in the corticomotor pathways, related to the masseter muscle. Fifteen healthy volunteers performed six series with ten trials of an oral sensorimotor task. The task was to manipulate and position a spherical chocolate candy in between the anterior teeth and split it into two equal halves. The precision of the task performance was evaluated by comparing the ratio between the two split halves. A series of "hold-and-split" tasks was also performed before and after the training. The hold force and split force along with the electromyographic (EMG) activity of jaw muscles were recorded. Motor-evoked potentials and cortical motor maps of the right masseter muscle were evoked by transcranial magnetic stimulation. There was a significant effect of series on the precision of the task performance during the short-term oral sensorimotor training (P < 0.002). The hold force during the "hold-and-split" task was significantly lower after training than before the short-term training (P = 0.011). However, there was no change in the split force and the EMG activity of the jaw muscles before and after the training. Further, there was a significant increase in the amplitude of the motor-evoked potentials (P < 0.016) and in the motor cortex map areas (P = 0.033), after the short-term oral sensorimotor training. Therefore, short-term oral sensorimotor task training increased the precision of task performance and induced signs of neuroplastic changes in the corticomotor pathways, related to the masseter muscle. PMID:26914481

  12. Use of Aripiprazole Long Acting Injection in Negative Symptoms of Schizophrenia

    PubMed Central

    James, Suneeta; Kapugama, Chaya; Al-Uzri, Mohammed

    2016-01-01

    Background. Evidence for the efficacious use of second-generation antipsychotics for the treatment of negative symptoms in schizophrenia is scant. Case Presentation. We report the case of a 34-year-old female of Afro-Caribbean origin, who presented with prominent negative symptoms of schizophrenia and was successfully treated with aripiprazole long acting injection. Within a period of six to nine months, the patient returned to her premorbid level of functioning. Conclusion. Aripiprazole long acting injection promises benefits in the treatment of negative symptoms of schizophrenia. Further research needs to be conducted on the use of this drug. PMID:26981301

  13. Patterns of faecal nematode egg shedding after treatment of sheep with a long-acting formulation of moxidectin.

    PubMed

    Crilly, James Patrick; Jennings, Amy; Sargison, Neil

    2015-09-15

    Much of the current information on the effects of long-acting anthelmintics on nematode populations derives either from research farms or mathematical models. A survey was performed with the aim of establishing how moxidectin is currently being used on sheep farms in the south-east of Scotland. A study was undertaken on a subsection of the surveyed farms to examine the effects of long-acting moxidectin treatments in both spring and autumn on faecal nematode egg output. The survey showed that whole flock treatments of injectable 2% moxidectin were used to control sheep scab on 21% of farms. Injectable 2% moxidectin and oral moxidectin were used to control the periparturient rise in faecal nematode egg shedding by ewes on 13% and 55% of farms respectively. The effects of injectable 2% moxidectin treatment on faecal nematode egg shedding post-treatment in both the autumn and spring were investigated by faecal nematode egg counts at the time of treatment and at 2-weekly interval thereafter on eight and six farms in the autumn and spring, respectively. Faecal egg shedding recommenced at 8 weeks (autumn) and 4 weeks (spring) post-treatment. Counts increased to a peak and then declined. The mean (95% confidence interval) peak counts post-treatment were 2.8 (0.6, 5.1), 3.6 (1.7, 5.5) and 53.5 (25.1, 82.0) eggs per gram (EPG) for autumn-treated ewes, autumn-treated lambs and spring-treated ewes respectively. The spring treated sheep showed a statistically significantly earlier return to faecal egg shedding (p=0.0125, p=0.0342) compared to both other groups, statistically significantly higher peak in egg counts than the autumn treated sheep (p<0.001) and a statistically significantly longer period of positive egg counts (p=0.0148). There was no statistically significant difference in the timing of the peak FECs between autumn and spring (p=0.211). The FECs of all groups of sheep treated with an injectable long-acting formulation of moxidectin became positive earlier than

  14. Introduction of postabortion contraception, prioritizing long-acting reversible contraceptives, in the principal maternity hospital of Gabon.

    PubMed

    Mayi-Tsonga, Sosthène; Obiang, Pamphile Assoumou; Minkobame, Ulysse; Ngouafo, Doris; Ambounda, Nathalie; de Souza, Maria Helena

    2014-07-01

    A prospective, descriptive, analytic study was conducted at the Centre Hospitalier de Libreville in Gabon between February and September 2013 to evaluate acceptance of long-acting reversible contraceptives (LARC) and depot-medroxyprogesterone acetate (DMPA) following abortion. Women received counseling on the combined oral pill, DMPA, copper intrauterine devices (IUDs), and implants. The association between sociodemographic and clinical characteristics, knowledge of contraceptives, and acceptance was analyzed. Of the 383 women admitted with abortion complications, 206 (53.7%) knew of no systemic contraceptives. The best-known method was the oral pill (42.0%). Only 14 women (3.6%) knew of a LARC method (IUD or implants) and only 2 (0.5%) said the injectable was their best-known method. Over 90% accepted a modern contraceptive method after abortion. Two-thirds (66.8%) chose the pill, 14.6% DMPA, and 9.3% a LARC method. Only 9.1% of the women refused to initiate use of any method.

  15. Development of long-acting bioadhesive vaginal gels of oxybutynin: formulation, in vitro and in vivo evaluations.

    PubMed

    Tuğcu-Demiröz, Fatmanur; Acartürk, Füsun; Erdoğan, Deniz

    2013-11-30

    Overactive bladder (OAB) and vaginal dryness are common problems after menopause. Oxybutynin (OXY) is an antimuscarinic agent that has been available for more than 30 years in the treatment of OAB patients. The aim of the work reported in this paper was to develop long acting mucoadhesive gel formulations of OXY and to investigate their effects on blood levels compared to those of oral OXY immediate release tablets, in rabbits. Mucoadhesive gels were prepared with chitosan, hydroxypropyl methylcellulose (HPMC K100M) and Poloxamer 407 (Pluronic F 127). The physicopharmaceutical properties of gels were evaluated. The gel formulation which was prepared with HPMC K100M, exhibited the highest viscosity, the greatest adhesiveness, cohesiveness and mucoadhesion values. The formulation which was prepared from HPMC K100M showed suitable permeation characteristics across the vaginal mucosa. Comparative bioavailability studies were carried out on rabbits with vaginal HPMC gel, vaginal chitosan gel, vaginal OXY solution and commercially available oral Üropan tablets. It was concluded that the highest AUC and relative bioavailability values were obtained for the bioadhesive vaginal gel formulation prepared with HPMC K100M. Therefore, the mucoadhesive vaginal gels of OXY can be a promising and innovative alternative therapeutic system for the treatment of OAB. It can be safely used in cases of overactive bladder and as well as vaginal dryness after menopause.

  16. Hypercalcemia appeared in a patient with glucagonoma treated with octreotide acetate long-acting release.

    PubMed

    Rui, Min; Li, Li; Jiang-Feng, Mao; Feng, Gu; Hui-Juan, Zhu; Wen-Hui, Li; Yu-Xiu, Li

    2012-09-01

    PABCREATIC neuroendocrine tumours are uncommon neoplasms of the pancreas. They may cause a clinical syndrome due to hormone overproduction. Glucagonoma is a rare kind of pancreatic tumors. Here we report a case of glucagonoma. Hypercalcemia occurred when the patient underwent octreotide acetate long-acting release.

  17. Does Prolonged Therapy with a Long-Acting Stimulant Suppress Growth in Children with ADHD?

    ERIC Educational Resources Information Center

    Spencer, Thomas J.; Faraone, Stephen V.; Biederman, Joseph; Lerner, Marc; Cooper, Kimberly M.; Zimmerman, Brenda

    2006-01-01

    Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the…

  18. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrino...

  19. Long-acting muscarinic antagonist + long-acting beta agonist versus long-acting beta agonist + inhaled corticosteroid for COPD: A systematic review and meta-analysis.

    PubMed

    Horita, Nobuyuki; Miyazawa, Naoki; Tomaru, Koji; Inoue, Miyo; Kaneko, Takeshi

    2015-11-01

    Some trials have been conducted to compare long-acting muscarinic antagonist (LAMA) + long-acting beta agonist (LABA) versus LABA + inhaled corticosteroids (ICS) for chronic obstructive pulmonary disease (COPD), but no meta-analysis were reported. Two investigators independently searched for eligible articles using the PubMed, Web of Science and Cochrane databases. Articles in authors' reference files were also regarded as candidates. The eligibility criteria for the current meta-analysis were original trials written in English comparing the impact of LAMA + LABA and LABA + ICS for COPD patients. A pooled value for the continuous value was calculated using the genetic inverse variance method for mean difference. Incidence of events was evaluated using the odds ratio (OR). Minimal clinically important difference were 50 mL for forced expiratory volume in 1 s (FEV1 ), four points for St George Respiratory Questionnaire (SGRQ) and one point for transition dyspnoea index (TDI). We included seven randomized controlled trials and one cross-over trial with follow-up period of 6-26 weeks. Compared with LABA + ICS, LAMA + LABA led to significantly greater improvements of trough FEV1 by 71 (95% CI: 48-95) mL, TDI by 0.38 points (95% CI: 0.17-0.58), less exacerbations with an OR of 0.77 (95% CI: 0.62-0.96) and less pneumonia with an OR of 0.28 (95% CI: 0.12-0.68). Frequencies of any adverse event, serious adverse event, adverse event leading to discontinuation, all-cause death and change of total score of SGRQ were not different in both arms. LAMA + LABA might be a better option for treating COPD than LABA + ICS. PMID:26235837

  20. Serial follow-up of presurgical treatment using pasireotide long-acting release with or without octreotide long-acting release for naïve active acromegaly.

    PubMed

    Chang, Jan-Shun; Tseng, Ham-Min; Chang, Tien-Chun

    2016-06-01

    The aim of the present study was to evaluate the serial changes of GH and IGF-1 in seven patients with naïve, active acromegaly following presurgical treatment of the somatostatin analog pasireotide long-acting release (LAR) and octreotide LAR. The patients were treated with pasireotide LAR with or without octreotide LAR for two years and underwent transsphenoidal adenomectomy. After treatment with the somatostatin analogs, the surgical cure rate was similar to that in patients who underwent transsphenoidal surgery alone. Diabetes insipidus was not identified in any patients after the operation. Pasireotide LAR was effective on GH as well as IGF-1 suppression and tumor size decreasing when used as the primary therapy. Future large-population studies to investigate the surgical curative rate after presurgical treatment with somatostatin analogs in patients with acromegaly and macroadenomas close to the cavernous sinus are warranted. However, that hyperglycemia developed following pre-surgical treatment with pasireotide should take into consideration. PMID:27117887

  1. PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE FREE ACID, A LONG-ACTING CEPHALOSPORIN, IN AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER).

    PubMed

    Kilburn, Jennifer J; Cox, Sherry K; Backues, Kay A

    2016-06-01

    Antibiotic usage is a vital component of veterinary medicine but the unique anatomy of some species can make administration difficult. The objective of this study was to determine the pharmacokinetic parameters of ceftiofur crystalline free acid (CCFA), a long-acting cephalosporin antibiotic, after parenteral administration in American flamingos ( Phoenicopterus ruber ). A dose of 10 mg/kg of CCFA was administered intramuscularly to 11 birds and blood was collected at various time points from 0 to 192 hr. Pharmacokinetic parameters for ceftiofur equivalents were determined and reached levels above minimum inhibitory concentrations of various bacterial organisms in other avian species through 96 hr in 9/11 birds. Based on these findings and comparison to other avian studies, ceftiofur crystalline free acid appears to be a long-acting antibiotic option for American flamingos. Administration of this antibiotic should be utilized in conjunction with culture and sensitivity of suspected pathogens.

  2. PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE FREE ACID, A LONG-ACTING CEPHALOSPORIN, IN AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER).

    PubMed

    Kilburn, Jennifer J; Cox, Sherry K; Backues, Kay A

    2016-06-01

    Antibiotic usage is a vital component of veterinary medicine but the unique anatomy of some species can make administration difficult. The objective of this study was to determine the pharmacokinetic parameters of ceftiofur crystalline free acid (CCFA), a long-acting cephalosporin antibiotic, after parenteral administration in American flamingos ( Phoenicopterus ruber ). A dose of 10 mg/kg of CCFA was administered intramuscularly to 11 birds and blood was collected at various time points from 0 to 192 hr. Pharmacokinetic parameters for ceftiofur equivalents were determined and reached levels above minimum inhibitory concentrations of various bacterial organisms in other avian species through 96 hr in 9/11 birds. Based on these findings and comparison to other avian studies, ceftiofur crystalline free acid appears to be a long-acting antibiotic option for American flamingos. Administration of this antibiotic should be utilized in conjunction with culture and sensitivity of suspected pathogens. PMID:27468016

  3. Fast and long-acting antibacterial properties of chitosan-Ag/polyvinylpyrrolidone nanocomposite films.

    PubMed

    Wang, Bai-Liang; Liu, Xiang-Sheng; Ji, Ying; Ren, Ke-Feng; Ji, Jian

    2012-09-01

    Infection associated with medical devices is one of the most frequent complications of modern medical biomaterials. Preparation of antibacterial films on the medical devices is a great challenge owing to bactericidal efficiency, long acting and biocompatibility. In this study, silver nanoparticles (Ag NPs) doped chitosan/polyvinylpyrrolidone (PVP) films were successfully prepared by dip coating method. The nanocomposite films with spherical Ag NPs (diameters in 10-50 nm) were stable after being immersed in PBS for 35 days. Through regulating the concentration of AgNO3, the nanocomposite films showed good cell compatibility. The nanocomposite films could eliminate 100% Staphylococcus aureus (ATCC 6538) and Escherichia coli (ATCC 8739) in 5 min and had favorable long-acting antibacterial property. The increase of PVP amount obviously enhanced anti-adhesion activity of the nanocomposite film. Such nanocomposite films can be expected to have good potential in biomaterials applications.

  4. Nocturnal Hypoglycemia: Answering the Challenge With Long-acting Insulin Analogs

    PubMed Central

    Brunton, Stephen A.

    2007-01-01

    Background Nocturnal hypoglycemia may be the most common type of hypoglycemia in individuals with diabetes using insulin and is particularly worrisome because it often goes undetected and may lead to unconsciousness and even death in severe cases. Objectives The prevalence, causes, and consequences of nocturnal hypoglycemia as well as detection and prevention strategies are reviewed, including the use of long-acting insulin analogs, which offer more physiologic and predictable time-action profiles than traditional human basal insulin. Data Sources A total of 307 publications (151 PubMed; 104 Adis; 52 BIOSIS) were reviewed. Review Methods Relevant trials were found by searching for “(detemir OR glargine) AND nocturnal AND (hypoglycemia OR hypoglycaemia) AND diabetes.” To capture trials that may not have specified “nocturnal” in the title or abstract text but still reported nocturnal hypoglycemia data, a supplemental search of PubMed using “(detemir OR glargine) AND (nocturnal OR hypoglycemia OR hypoglycaemia) AND diabetes” was undertaken. Results A review of these trials found that patients with type 1 and type 2 diabetes mellitus have a lower risk for nocturnal hypoglycemia when receiving long-acting insulin analogs (insulin detemir or insulin glargine), provided that glycemic control is comparable to that provided by traditional human basal insulin. Long-acting insulin analogs may be the best option to provide basal insulin coverage in patients who do not choose or require continuous subcutaneous insulin infusion. Conclusions Randomized clinical trials suggest that the long-acting insulin analogs are associated with a lower risk for nocturnal hypoglycemia than neutral protamine Hagedorn without sacrificing glycemic control. PMID:17955093

  5. [Slow-release salbutamol in the treatment of nocturnal asthma. Result of a comparative study vs. long-acting theophylline].

    PubMed

    Arnaud, A; Michel, F B; Desfougères, J L; Pappo, M

    1991-01-01

    In a multicentre, randomized, cross-over double-blind, double placebo trial the effectiveness and tolerability of slow-release oral salbutamol (SRS) were compared with those of long-acting (LA) theophylline (T) in the treatment of nocturnal asthma of adults. Forty-nine patients (mean age 37 years) entered the study after a pre-trial period during which a placebo and inhaled salbutamol were used as reference and to test the criteria of inclusion. The number of awakenings due to asthma symptoms was the same with SRS, and T, falling from 1.27 in the pre-trial period to 0.44 under SRS and 0.42 under T. The scores of nocturnal asthma symptoms were improved with both types of treatment. The number of puffs of inhaled salbutamol necessary during the night decreased from 1.94 in the pre-trial period to 1.15 under SRS and 0.92 under T. The number of patients improved was exactly the same in both groups. The ventilatory parameters measured by respiratory function tests at different visits and daily by the patients themselves were also improved. The principal minor side-effects were tremor (5 cases) and irritability (3 cases) with SRS, and nausea (6 cases), headache (3 cases) and asthenia (2 cases) with T; an overdose of T resulted in malaise in one patients. It is concluded that slow-release oral salbutamol administered in doses of 8 mg b.d. is effective in controlling nocturnal asthma, easy to take and very well tolerated.

  6. The role of inhaled long-acting beta-2 agonists in the management of asthma.

    PubMed Central

    Kelly, H. William; Harkins, Michelle S.; Boushey, Homer

    2006-01-01

    The role of inhaled beta-2 agonists in the management of asthma has changed significantly over the last several years. This review outlines the most recent understanding of the pathophysiology of asthma and the studies that define the roles that both short- and long-acting beta-2 agonists play in therapy for this disease. A concentration on the clinical pharmacology and genetic implications for clinical use of this class of drugs in accordance with the national and international guidelines are described. PMID:16532973

  7. Chronic oral ingestion of l-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans

    PubMed Central

    Wall, Benjamin T; Stephens, Francis B; Constantin-Teodosiu, Dumitru; Marimuthu, Kanagaraj; Macdonald, Ian A; Greenhaff, Paul L

    2011-01-01

    We have previously shown that insulin increases muscle total carnitine (TC) content during acute i.v. l-carnitine infusion. Here we determined the effects of chronic l-carnitine and carbohydrate (CHO; to elevate serum insulin) ingestion on muscle TC content and exercise metabolism and performance in humans. On three visits, each separated by 12 weeks, 14 healthy male volunteers (age 25.9 ± 2.1 years, BMI 23.0 ± 0.8 kg m−2) performed an exercise test comprising 30 min cycling at 50%, 30 min at 80%, then a 30 min work output performance trial. Muscle biopsies were obtained at rest and after exercise at 50% and 80% on each occasion. Following visit one, volunteers ingested either 80 g of CHO (Control) or 2 g of l-carnitine-l-tartrate and 80 g of CHO (Carnitine) twice daily for 24 weeks in a randomised, double blind manner. All significant effects reported occurred after 24 weeks. Muscle TC increased from basal by 21% in Carnitine (P < 0.05), and was unchanged in Control. At 50%, the Carnitine group utilised 55% less muscle glycogen compared to Control (P < 0.05) and 31% less pyruvate dehydrogenase complex (PDC) activation compared to before supplementation (P < 0.05). Conversely, at 80%, muscle PDC activation was 38% higher (P < 0.05), acetylcarnitine content showed a trend to be 16% greater (P < 0.10), muscle lactate content was 44% lower (P < 0.05) and the muscle PCr/ATP ratio was better maintained (P < 0.05) in Carnitine compared to Control. The Carnitine group increased work output 11% from baseline in the performance trial, while Control showed no change. This is the first demonstration that human muscle TC can be increased by dietary means and results in muscle glycogen sparing during low intensity exercise (consistent with an increase in lipid utilisation) and a better matching of glycolytic, PDC and mitochondrial flux during high intensity exercise, thereby reducing muscle anaerobic ATP production. Furthermore, these changes were associated with an

  8. Cost and carbon burden of long-acting injections: a sustainable evaluation.

    PubMed

    Maughan, Daniel L; Lillywhite, Rob; Cooke, Matthew

    2016-06-01

    Aims and method This study explores the economic cost and carbon footprint associated with current patterns of prescribing long-term flupentixol decanoate long-acting injections. We conducted an analysis of prescription data from a mental health trust followed by economic and carbon cost projections using local and national data. Results A reduction of £300 000 could be achieved across England by improving prescribing behaviour, which equates to £250 per patient per year and 170 000 kg CO2e. These savings are unlikely to be released as cash from the service, but will lead to higher-value service provision at the same or lower cost. Most of these carbon emissions are attributable to the carbon footprint of the appointment - 88 000 kg CO2e (including energy use and materials used) and the overprescribing of medication - 66 000 kg CO2e. Clinical implications Psychiatrists need to review their prescribing practice of long-acting injections to reduce their impact on the National Health Service financial budget and the environment. PMID:27280033

  9. Adjunctive and Long-Acting Nanoformulated Antiretroviral Therapies for HIV-associated neurocognitive disorders

    PubMed Central

    Gendelman, Howard E.; Gelbard, Harris A.

    2014-01-01

    Purpose of review This review focuses on current and future strategies to modulate neuroinflammation while reducing residual viral burden in the central nervous system (CNS). This has been realized by targeted long acting antiretroviral nano- and adjunctive therapies being developed for HIV infected people. Our ultimate goal is to eliminate virus from its CNS reservoirs and, in so doing, reverse the cognitive and motor dysfunctions seen in HIV-associated neurocognitive disorders (HAND). Recent findings Herein, we highlight our laboratories development of adjunctive and nanomedicine therapies for HAND. An emphasis is placed on drug-drug interactions that target both the viral life cycle and secretory pro-inflammatory neurotoxic factors and signaling pathways. Summary Antiretroviral therapy (ART) has improved the quality and duration of life for people living with HIV-1. A significant long-term comorbid illness is HAND. Symptoms, while reduced in severity, are common. Disease occurs, in part, through continued low-level viral replication inducing secondary glial neuroinflammatory activities. Our recent works and those of others have seen disease attenuated in animal models through the use of adjunctive and long-acting reservoir targeted nanoformulated ART. The translation of these inventions from animals to humans is the focus of this review. PMID:25226025

  10. Impact of risperidone long acting injection on resource utilization in psychiatric secondary care.

    PubMed

    Taylor, M; Currie, A; Lloyd, K; Price, M; Peperell, Kate

    2008-03-01

    Risperidone long acting injection (RLAI) is the only long acting atypical antipsychotic available in the UK. Its impact on NHS resource use has not been widely studied. This review of medical records was conducted to quantify the impact of RLAI on NHS psychiatric secondary care resource use, primarily in terms of episodes of inpatient hospital care 12 months before and 12 months after RLAI initiation. Data on number of hospitalizations and hospital bed days were collected retrospectively, from patient notes and hospital databases in four acute psychiatric units in the UK for all individuals with a diagnosis of schizophrenia or schizoaffective disorder who were prescribed RLAI more than 12 months previously. Data were collected on 100 individuals (58 male) with a mean age 40.8 years (range 19-70). The median duration of illness before RLAI initiation was 12 years (range six months to 43 years). There were 62 admissions in the 12 months pre-RLAI, falling to 22 admissions in the 12 months post-RLAI. Number of admissions, we argue, offer a more reliable indicator of the impact of treatment than total hospital bed days in this type of study. In this study there were 40 fewer admissions in the 12 months after RLAI was initiated compared with the previous 12 months. This is important as readmission is a good proxy measure of relapse, and adherence to medication is known to be a key factor in relapse prevention. PMID:18308820

  11. Cost and carbon burden of long-acting injections: a sustainable evaluation

    PubMed Central

    Maughan, Daniel L.; Lillywhite, Rob; Cooke, Matthew

    2016-01-01

    Aims and method This study explores the economic cost and carbon footprint associated with current patterns of prescribing long-term flupentixol decanoate long-acting injections. We conducted an analysis of prescription data from a mental health trust followed by economic and carbon cost projections using local and national data. Results A reduction of £300 000 could be achieved across England by improving prescribing behaviour, which equates to £250 per patient per year and 170 000 kg CO2e. These savings are unlikely to be released as cash from the service, but will lead to higher-value service provision at the same or lower cost. Most of these carbon emissions are attributable to the carbon footprint of the appointment – 88 000 kg CO2e (including energy use and materials used) and the overprescribing of medication – 66 000 kg CO2e. Clinical implications Psychiatrists need to review their prescribing practice of long-acting injections to reduce their impact on the National Health Service financial budget and the environment. PMID:27280033

  12. The differential effects of short- and long-acting benzodiazepines upon nocturnal sleep and daytime performance.

    PubMed

    Roth, T; Hartse, K M; Zorick, F J; Kaffeman, M E

    1980-01-01

    Hypnotic drugs are the most frequent medical intervention for providing symptomatic relief of insomnia. Both effective amelioration of the insomnia complaint and the minimization of residual effects upon daytime performance must be considered in the selection of these medications. Data are presented here which compare the effects of short- and long-acting benzodiazepines upon sleep and upon waking performance. Unlike short-acting hypnotics with half-lives of up to 10 h (lorazepam, triazolam and temazepam), long-acting hypnotics with half-lives of up to 100 h (flurazepam, ketazolam) produce suppression of both REM and Stage 3--4 sleep which persists during the drug withdrawal (recovery) period. The half-life of hypnotics is also directly related to the duration of residual effects upon daytime performance. Hypnotics with long half-lives (flurazepam) produce more prolonged performance decrements than hypnotics with short half-lives (temazepam). In insomniacs, both effects upon sleep and upon walking performance must be considered in the selection of a hypnotic.

  13. A long-acting GH receptor antagonist through fusion to GH binding protein

    PubMed Central

    Wilkinson, Ian R.; Pradhananga, Sarbendra L.; Speak, Rowena; Artymiuk, Peter J.; Sayers, Jon R.; Ross, Richard J.

    2016-01-01

    Acromegaly is a human disease of growth hormone (GH) excess with considerable morbidity and increased mortality. Somatostatin analogues are first line medical treatment but the disease remains uncontrolled in up to 40% of patients. GH receptor (GHR) antagonist therapy is more effective but requires frequent high-dose injections. We have developed an alternative technology for generating a long acting potent GHR antagonist through translational fusion of a mutated GH linked to GH binding protein and tested three candidate molecules. All molecules had the amino acid change (G120R), creating a competitive GHR antagonist and we tested the hypothesis that an amino acid change in the GH binding domain (W104A) would increase biological activity. All were antagonists in bioassays. In rats all antagonists had terminal half-lives >20 hours. After subcutaneous administration in rabbits one variant displayed a terminal half-life of 40.5 hours. A single subcutaneous injection of the same variant in rabbits resulted in a 14% fall in IGF-I over 7 days. In conclusion: we provide proof of concept that a fusion of GHR antagonist to its binding protein generates a long acting GHR antagonist and we confirmed that introducing the W104A amino acid change in the GH binding domain enhances antagonist activity. PMID:27731358

  14. Pharmacokinetics of a long-acting ceftiofur formulation (ceftiofur crystalline free acid) in the ball python (Python regius).

    PubMed

    Adkesson, Michael J; Fernandez-Varon, Emilio; Cox, Sherry; Martín-Jiménez, Tomás

    2011-09-01

    The objective of this study was to determine the pharmacokinetics of a long-acting formulation of ceftiofur crystalline-free acid (CCFA) following intramuscular injection in ball pythons (Python regius). Six adult ball pythons received an injection of CCFA (15 mg/kg) in the epaxial muscles. Blood samples were collected by cardiocentesis immediately prior to and at 0.5, 1, 2, 4, 8, 12, 18, 24, 48, 72, 96, 144, 192, 240, 288, 384, 480, 576, 720, and 864 hr after CCFA administration. Plasma ceftiofur concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was applied to the data. Maximum plasma concentration (Cmax) was 7.096 +/- 1.95 microg/ml and occurred at (Tmax) 2.17 +/- 0.98 hr. The area under the curve (0 to infinity) for ceftiofur was 74.59 +/- 13.05 microg x h/ml and the elimination half-life associated with the terminal slope of the concentration-time curve was 64.31 +/- 14.2 hr. Mean residence time (0 to infinity) was 46.85 +/- 13.53 hr. CCFA at 15 mg/kg was well tolerated in all the pythons. Minimum inhibitory concentration (MIC) data for bacterial isolates from snakes are not well established. For MIC values of < or =0.1 microg/ml, a single dose of CCFA (15 mg/kg) provides adequate plasma concentrations for at least 5 days in the ball python. For MICs > or =0.5 microg/ml, more frequent dosing or a higher dosage may be required.

  15. Effectiveness of long-acting risperidone in a patient with comorbid intellectual disability, catatonic schizophrenia, and oneiroid syndrome.

    PubMed

    Serata, Daniele; Rapinesi, Chiara; Kotzalidis, Georgios Demetrios; Alessi, Maria Chiara; Janiri, Delfina; Massolo, Anna Claudia; Ferri, Vittoria Rachele; Criscuolo, Silvia; Callovini, Gemma; Angeletti, Gloria; Girardi, Paolo; Del Casale, Antonio

    2015-01-01

    A patient with comorbid intellectual disability, catatonic schizophrenia, and recurrent oneiroid state of consciousness improved on long-acting risperidone and remains well at the three-year follow-up. We report a case treated with 50 mg long-acting risperidone administered every 14 days, who has been followed-up for three years. We studied his regional cerebral blood flow through technetium-99 m hexamethylpropyleneamine oxime single-photon emission computed tomography after two years of treatment. Symptoms of catatonic schizophrenia improved after two months of treatment, followed suit by oneiroid syndrome remission. Two years later, his brain perfusion was normal. No side effect has occurred since the patient was started on long-acting risperidone. Long-acting risperidone proved to be safe and effective in treating symptoms of catatonia and oneiroid syndrome. PMID:26443711

  16. Strengthening Postabortion Family Planning Services in Ethiopia: Expanding Contraceptive Choice and Improving Access to Long-Acting Reversible Contraception

    PubMed Central

    Samuel, Melaku; Fetters, Tamara; Desta, Demeke

    2016-01-01

    ABSTRACT Where unmet need for the safest, most effective, and long-acting reversible contraceptives (LARCs) is very high, the health system and partners need to implement problem-solving, locally feasible, and comprehensive family planning delivery strategies. Because young and unmarried women are most at risk for unintended pregnancy and repeat abortion due to poor access to contraceptive services, postabortion family planning (PAFP) is a key component in such strategies. In Southern Nations, Nationalities, and People’s Region, Ethiopia, Ipas implemented health system strengthening efforts from fiscal year (FY) 2010 (July 2009 to June 2010) to FY 2014 (July 2013 to June 2014) to improve the quality of PAFP services and expand method choice in 101 public facilities. The intervention significantly improved PAFP uptake at the project sites. Specifically, the proportion of abortion clients receiving LARCs progressively improved during the intervention period. The proportion of abortion clients who left the facilities with a contraceptive method increased from 58% in FY 2010 to 83% in FY 2014. The share of method mix for LARCs rose from 2% in FY 2010 to 55% in FY 2014, while the share for condoms, injectables, and oral contraceptives declined from 98% to 45%. Implant use rose from 2% in FY 2010 to 43% in FY 2014, while the use of intrauterine devices increased from 0.1% in FY 2010 to 12% in FY 2014. A larger proportion of PAFP users received LARCs at health centers, where midwives and nurses are the primary providers, than at hospitals (59% versus 37%, respectively). A broader method mix can satisfy clients with a variety of needs, a key factor for higher uptake of more effective methods and program success. Further evidence-based interventions need to be implemented to improve the quality of PAFP in a feasible and replicable strategy that addresses unmet need for modern contraceptive methods. PMID:27540126

  17. Strengthening Postabortion Family Planning Services in Ethiopia: Expanding Contraceptive Choice and Improving Access to Long-Acting Reversible Contraception.

    PubMed

    Samuel, Melaku; Fetters, Tamara; Desta, Demeke

    2016-08-11

    Where unmet need for the safest, most effective, and long-acting reversible contraceptives (LARCs) is very high, the health system and partners need to implement problem-solving, locally feasible, and comprehensive family planning delivery strategies. Because young and unmarried women are most at risk for unintended pregnancy and repeat abortion due to poor access to contraceptive services, postabortion family planning (PAFP) is a key component in such strategies. In Southern Nations, Nationalities, and People's Region, Ethiopia, Ipas implemented health system strengthening efforts from fiscal year (FY) 2010 (July 2009 to June 2010) to FY 2014 (July 2013 to June 2014) to improve the quality of PAFP services and expand method choice in 101 public facilities. The intervention significantly improved PAFP uptake at the project sites. Specifically, the proportion of abortion clients receiving LARCs progressively improved during the intervention period. The proportion of abortion clients who left the facilities with a contraceptive method increased from 58% in FY 2010 to 83% in FY 2014. The share of method mix for LARCs rose from 2% in FY 2010 to 55% in FY 2014, while the share for condoms, injectables, and oral contraceptives declined from 98% to 45%. Implant use rose from 2% in FY 2010 to 43% in FY 2014, while the use of intrauterine devices increased from 0.1% in FY 2010 to 12% in FY 2014. A larger proportion of PAFP users received LARCs at health centers, where midwives and nurses are the primary providers, than at hospitals (59% versus 37%, respectively). A broader method mix can satisfy clients with a variety of needs, a key factor for higher uptake of more effective methods and program success. Further evidence-based interventions need to be implemented to improve the quality of PAFP in a feasible and replicable strategy that addresses unmet need for modern contraceptive methods. PMID:27540126

  18. Oral supplementations with free and dipeptide forms of L-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins.

    PubMed

    Cruzat, Vinicius F; Pantaleão, Lucas C; Donato, José; de Bittencourt, Paulo Ivo Homem; Tirapegui, Julio

    2014-03-01

    Sepsis is a leading cause of death in intensive care units worldwide. Low availability of glutamine contributes to the catabolic state of sepsis. L-Glutamine supplementation has antioxidant properties and modulates the expression of heat shock proteins (HSPs). This study investigated the effects of oral supplementation with L-glutamine plus L-alanine (GLN+ALA), both in the free form and L-alanyl-L-glutamine dipeptide (DIP), on glutamine-glutathione (GSH) axis and HSPs expression in endotoxemic mice. B6.129F2/J mice were subjected to endotoxemia (lipopolysaccharides from Escherichia coli, 5 mg.kg(-1), LPS group) and orally supplemented for 48 h with either L-glutamine (1 g.kg(-1)) plus L-alanine (0.61 g.kg(-1)) (GLN+ALA-LPS group) or 1.49 g.kg(-1) of DIP (DIP-LPS group). Endotoxemia reduced plasma and muscle glutamine concentrations [relative to CTRL group] which were restored in both GLN+ALA-LPS and DIP-LPS groups (P<.05). In supplemented groups were re-established GSH content and intracellular redox status (GSSG/GSH ratio) in circulating erythrocytes and muscle. Thiobarbituric acid reactive substance was 4-fold in LPS treated mice relative to the untreated CTRL group, and plasma TNF-α and IL-1β levels were attenuated by the supplements. Heat shock proteins 27, 70 and 90 (protein and mRNA) were elevated in the LPS group and were returned to basal levels (relative to CTRL group) in both GLN+ALA-LPS and DIP-LPS groups. Supplementations to endotoxemic mice resulted in up-regulation of GSH reductase, GSH peroxidase and glutamate cysteine ligase mRNA expression in muscle. In conclusion, oral supplementations with GLN+ALA or DIP are effective in reversing the conditions of LPS-induced deleterious impact on glutamine-GSH axis in mice under endotoxemia.

  19. The antioxidant status and oxidative stability of muscle from lambs receiving oral administration of Artemisia herba alba and Rosmarinus officinalis essential oils.

    PubMed

    Aouadi, Dorra; Luciano, Giuseppe; Vasta, Valentina; Nasri, Saida; Brogna, Daniela M R; Abidi, Sourour; Priolo, Alessandro; Salem, Hichem Ben

    2014-06-01

    The effect of the dietary supplementation to lambs of essential oils (EOs) from rosemary (Rosmarinus officinalis) and artemisia (Artemisia herba alba) on the antioxidant status of muscle and on meat oxidative stability was studied. Eighteen Barbarine lambs were divided into 3 groups and for 95days received oat hay and concentrates. One group (C) was not supplemented, while the other two groups received 400mg/kg of EOs from rosemary (R400) or artemisia (A400). Both EOs possessed antioxidant properties and their oral administration improved the reducing and radical scavenging capacity of the muscle compared to the C treatment (P<0.01). Nevertheless, supplementing EOs did not exert protection against lipid oxidation and did not affect the colour stability in meat over 7days of aerobic storage.

  20. Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus.

    PubMed

    Andrews, Chasity D; Spreen, William R; Mohri, Hiroshi; Moss, Lee; Ford, Susan; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Bohm, Rudolf P; Cheng-Mayer, Cecilia; Hong, Zhi; Markowitz, Martin; Ho, David D

    2014-03-01

    GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP).

  1. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal.

    PubMed

    Brissos, Sofia; Veguilla, Miguel Ruiz; Taylor, David; Balanzá-Martinez, Vicent

    2014-10-01

    Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper's blending of experimental trials with observational research is particularly appropriate and effective. PMID:25360245

  2. Committee Opinion No. 670 Summary: Immediate Postpartum Long-Acting Reversible Contraception.

    PubMed

    2016-08-01

    Immediate postpartum long-acting reversible contraception (LARC) has the potential to reduce unintended and short-interval pregnancy. Women should be counseled about all forms of postpartum contraception in a context that allows informed decision making. Immediate postpartum LARC should be offered as an effective option for postpartum contraception; there are few contraindications to postpartum intrauterine devices and implants. Obstetrician-gynecologists and other obstetric care providers should discuss LARC during the antepartum period and counsel all pregnant women about options for immediate postpartum initiation. Education and institutional protocols are needed to raise clinician awareness and to improve access to immediate postpartum LARC insertion. Obstetrician-gynecologists and other obstetric care providers should incorporate immediate postpartum LARC into their practices, counsel women appropriately about advantages and risks, and advocate for institutional and payment policy changes to support provision. PMID:27454730

  3. Committee Opinion No. 670: Immediate Postpartum Long-Acting Reversible Contraception.

    PubMed

    2016-08-01

    Immediate postpartum long-acting reversible contraception (LARC) has the potential to reduce unintended and short-interval pregnancy. Women should be counseled about all forms of postpartum contraception in a context that allows informed decision making. Immediate postpartum LARC should be offered as an effective option for postpartum contraception; there are few contraindications to postpartum intrauterine devices and implants. Obstetrician-gynecologists and other obstetric care providers should discuss LARC during the antepartum period and counsel all pregnant women about options for immediate postpartum initiation. Education and institutional protocols are needed to raise clinician awareness and to improve access to immediate postpartum LARC insertion. Obstetrician-gynecologists and other obstetric care providers should incorporate immediate postpartum LARC into their practices, counsel women appropriately about advantages and risks, and advocate for institutional and payment policy changes to support provision. PMID:27454734

  4. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal.

    PubMed

    Brissos, Sofia; Veguilla, Miguel Ruiz; Taylor, David; Balanzá-Martinez, Vicent

    2014-10-01

    Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper's blending of experimental trials with observational research is particularly appropriate and effective.

  5. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal

    PubMed Central

    Veguilla, Miguel Ruiz; Taylor, David; Balanzá-Martinez, Vicent

    2014-01-01

    Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper’s blending of experimental trials with observational research is particularly appropriate and effective. PMID:25360245

  6. Let's talk about sex (again): advancing the conversation around long-acting reversible contraception for teenagers.

    PubMed

    Satterwhite, Catherine Lindsey; Ramaswamy, Megha

    2015-11-01

    Long-acting reversible contraception (LARC) has incredible potential for decreasing teenage pregnancy rates in the USA, but use among adolescents remains low. LARC methods, including intrauterine devices and implants, are recommended as first-line choices for teenagers by multiple medical professional associations. Barriers at the system, provider and patient level persist, but new demonstration projects, in addition to provisions of the Affordable Care Act, show great promise in facilitating LARC use. A renewed national discourse should acknowledge the reality that many US teenagers have sex, that LARC is safe and effective and that LARC offers an opportunity to prevent teenage pregnancy. By encouraging widespread access and use, a large, positive impact across multiple health and economic sectors can be achieved.

  7. Plasma corticosteroid levels in rats maintained on a long-acting naltrexone delivery system.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1978-04-01

    A long-acting delivery system for naltrexone has been described, which blocked the antinociceptive action of 10 mg kg-1 s.c. dose of morphine in rats for a period of 2 to 3 months. Male Wistar rats implanted s.c. with such a delivery system showed highly significant depression of plasma corticosteroid levels (40.2% in one week and 22.4 to 27.2% in 3 months) as compared to placebo pellet-implanted animals. Morphine-dependent male rats implanted with 75 mg morphine pellets showed a small (17.5%) but significant increase in plasma corticosteroid levels as compared to the placebo controls 72 hr. after pellet implantation. PMID:663407

  8. Biocompatible riboflavin laurate long-acting injectable nanosuspensions allowing sterile filtration.

    PubMed

    Hu, Xi; Lin, Xia; Gu, Yuechen; Liu, Zitong; Tang, Yilin; Zhang, Yu; Chen, Xi; Wang, Yanjiao; Tang, Xing

    2014-08-01

    The aim of this research was to prepare biocompatible riboflavin laurate (RFL) long-acting injectable nanosuspensions for intramuscular injection with a small particle size allowing sterile filtration. RFL nanosuspensions were manufactured by a precipitation-combined high-pressure homogenization method. Three kinds of mixed stabilizers-d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a primary stabilizer, and egg lecithin (PL-100M), Kollidon VA64, Kollidon S-630 as a secondary stabilizer, were separately applied to avoid further aggregation. In the three optimized formulations, the mean particle size of the RFL nanosuspensions was about 170 nm allowing sterilization by filtration. Results from transmission electron microscopy, differential scanning calorimeter, powder X-ray diffraction and Fourier transform infrared reflectance spectroscopy revealed that RFL existed as rod-like crystals. However, a few nano-spheres under 100 nm were found only when PL-100 was used as a secondary stabilizer, possibly due to TPGS and PL-100, which inserted into RFL during the process of crystallization and homogenization. In irritation testing, RFL long-acting injection (LAI) stabilized by TPGS and PL-100 led to mild paw-licking responses and a slight inflammatory reaction, which returned to normal by 14 d after administration. The endogenous PL-100 and nano-spheres with a small size may have contributed to the excellent biocompatibility. As a result, TPGS and PL-100 were selected as blended stabilizers to prepare the irritation-free RFL-LAI that could be sterilized by passage through a 0.22 μm millipore membrane filter.

  9. Biocompatible riboflavin laurate long-acting injectable nanosuspensions allowing sterile filtration.

    PubMed

    Hu, Xi; Lin, Xia; Gu, Yuechen; Liu, Zitong; Tang, Yilin; Zhang, Yu; Chen, Xi; Wang, Yanjiao; Tang, Xing

    2014-08-01

    The aim of this research was to prepare biocompatible riboflavin laurate (RFL) long-acting injectable nanosuspensions for intramuscular injection with a small particle size allowing sterile filtration. RFL nanosuspensions were manufactured by a precipitation-combined high-pressure homogenization method. Three kinds of mixed stabilizers-d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a primary stabilizer, and egg lecithin (PL-100M), Kollidon VA64, Kollidon S-630 as a secondary stabilizer, were separately applied to avoid further aggregation. In the three optimized formulations, the mean particle size of the RFL nanosuspensions was about 170 nm allowing sterilization by filtration. Results from transmission electron microscopy, differential scanning calorimeter, powder X-ray diffraction and Fourier transform infrared reflectance spectroscopy revealed that RFL existed as rod-like crystals. However, a few nano-spheres under 100 nm were found only when PL-100 was used as a secondary stabilizer, possibly due to TPGS and PL-100, which inserted into RFL during the process of crystallization and homogenization. In irritation testing, RFL long-acting injection (LAI) stabilized by TPGS and PL-100 led to mild paw-licking responses and a slight inflammatory reaction, which returned to normal by 14 d after administration. The endogenous PL-100 and nano-spheres with a small size may have contributed to the excellent biocompatibility. As a result, TPGS and PL-100 were selected as blended stabilizers to prepare the irritation-free RFL-LAI that could be sterilized by passage through a 0.22 μm millipore membrane filter. PMID:24188474

  10. Persistent High Restenosis After Local Intrawall Delivery of Long-Acting Steroids Before Coronary Stent Implantation.

    PubMed

    Reimers; Moussa; Akiyama; Kobayashi; Albiero; Di Francesco L; Di Mario C; Colombo

    1998-07-01

    OBJECTIVE: This pilot study was performed to evaluate the feasibility and safety of intrawall delivery of long acting steroids before stent implantation, testing the efficacy of this treatment in reducing intimal hyperplasia in lesions at high risk for restenosis. METHODS: In 24 patients (40 lesions) local intrawall drug delivery of methylprednisolone acetate, using a new catheter device, was attempted before elective stent implantation. Treated lesions were compared to a matched control group. RESULTS: Lesions were classified AHA/ACC type C in 47% of cases, had a mean lesion length of 13.6 +/- 9.1 mm, and a mean vessel diameter of 2.85 +/- 0.44 mm. In 9 cases (25%) chronic total occlusions were treated. Methylprednisolone acetate (mean 60 +/- 23 mg) was delivered in 36 lesions (21 patients; delivery success 90%) in the remaining 4 lesions (10%) the delivery device did not cross the lesion. After drug delivery 46 stents were implanted (1.2 stent/lesion; stented segment length 30.1 +/- 18.8 mm) using high pressure for stent expansion (mean 16.4 +/- 3.1 atm). Intracoronary ultrasound guidance was used in 64% of cases. Procedural and in-hospital complications were: Two non Q wave myocardial infarctions (8%) and one (3%) subacute stent thrombosis. Angiographic follow-up was obtained in all 36 treated lesions (100%) and the angiographic restenosis rate (³ 50% diameter stenosis) was 39%. A reduction of the incidence of restenosis compared to the matched control group was not observed. CONCLUSIONS: Long acting steroids could be delivered locally with high success and low complication rates. The restenosis rate remained high in a subset of unfavorable lesions with high risk for restenosis.

  11. Long-term remission in schizophrenia and schizoaffective disorder: results from the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE)

    PubMed Central

    Cavallaro, Roberto; Folnegović-Šmalc, Vera; Bidzan, Leszek; Emin Ceylan, Mehmet; Schreiner, Andreas

    2013-01-01

    Objective: The objective of this study was to report the long-term remission results from the ConstaTRE relapse prevention trial, in which clinically stable adults with schizophrenia or schizoaffective disorder treated with oral risperidone, olanzapine, or oral conventional antipsychotics were randomized to risperidone long-acting injectable (RLAI) or oral quetiapine, dosed according to package-insert recommendations. Methods: In the ConstaTRE trial, efficacy and tolerability were recorded for up to 24 months. This post hoc analysis presents remission data, defined, according to the Schizophrenia Working Group criteria, as achieving and maintaining eight core symptoms of schizophrenia that are mild or less over 6 months. Additional secondary outcome measures are also presented. Results: A total of 710 patients were randomized to RLAI (n = 355) or quetiapine (n = 355). Mean mode ± standard deviation (SD) drug doses were RLAI 33 ± 10 mg every 2 weeks and quetiapine 413 ± 159 mg daily. Full remission was achieved by 51.1% of patients with RLAI and 39.3% with quetiapine (p = 0.003). Mean ± SD of full remission durations were not significantly different with RLAI (540 ± 181 days) and quetiapine (508 ± 188 days). Overall tolerability was similar between treatment groups. Conclusions: Among stable patients with schizophrenia or schizoaffective disorder, remission was more likely after switching to RLAI than quetiapine. PMID:24167692

  12. [Pharmacokinetics and safety of aripiprazole long-acting injection, following multiple deltoid administrations in schizophrenia patients in Japan].

    PubMed

    Ishigooka, Jun; Noda, Takamasa; Nishiyama, Kosuke; Tamaru, Noriko; Shima, Tomoko; Yamasaki, Yumiko; Tadori, Yoshihiro

    2016-06-01

    Aripiprazole once-monthly (AOM) was previously approved for treatment of schizophrenia as monthly injections in the gluteal muscle. The deltoid muscle provides a more accessible injection site. The present study was conducted in Japanese schizophrenia patients as a 24-week, open-label trial that assessed the pharmacokinetics and safety of 5 sequential doses of AOM 400 mg (AOM 400) once every 4 weeks administered in the deltoid muscle. Patients treated with an oral atypical antipsychotic (other than aripiprazole) continued to receive their pre-study medication up to 14 days after the first AOM 400 injection. The completion rate was 76.5% (n = 13/17). Mean aripiprazole plasma C(min) almost reached steady-state by the fourth AOM 400 injection. After the fifth AOM 400 injection, mean aripiprazole AUC(28d), C(max) and C(min) were 165 μg x h/ml, 331 ng/ml and 201 ng/ml, respectively, which were similar to previously published pharmacokinetic parameters after the fifth gluteal injection of AOM 400. The most common treatment-emergent adverse event (TEAE) was injection site pain (35.3%). Most TEAEs were classified as mild in intensity. In conclusion, the deltoid injection of AOM can be considered an alternative route of administration, as deltoid and gluteal injections are interchangeable in terms of aripiprazole plasma concentrations, with no additional safety issues.

  13. [Pharmacokinetics and safety of aripiprazole long-acting injection, following multiple deltoid administrations in schizophrenia patients in Japan].

    PubMed

    Ishigooka, Jun; Noda, Takamasa; Nishiyama, Kosuke; Tamaru, Noriko; Shima, Tomoko; Yamasaki, Yumiko; Tadori, Yoshihiro

    2016-06-01

    Aripiprazole once-monthly (AOM) was previously approved for treatment of schizophrenia as monthly injections in the gluteal muscle. The deltoid muscle provides a more accessible injection site. The present study was conducted in Japanese schizophrenia patients as a 24-week, open-label trial that assessed the pharmacokinetics and safety of 5 sequential doses of AOM 400 mg (AOM 400) once every 4 weeks administered in the deltoid muscle. Patients treated with an oral atypical antipsychotic (other than aripiprazole) continued to receive their pre-study medication up to 14 days after the first AOM 400 injection. The completion rate was 76.5% (n = 13/17). Mean aripiprazole plasma C(min) almost reached steady-state by the fourth AOM 400 injection. After the fifth AOM 400 injection, mean aripiprazole AUC(28d), C(max) and C(min) were 165 μg x h/ml, 331 ng/ml and 201 ng/ml, respectively, which were similar to previously published pharmacokinetic parameters after the fifth gluteal injection of AOM 400. The most common treatment-emergent adverse event (TEAE) was injection site pain (35.3%). Most TEAEs were classified as mild in intensity. In conclusion, the deltoid injection of AOM can be considered an alternative route of administration, as deltoid and gluteal injections are interchangeable in terms of aripiprazole plasma concentrations, with no additional safety issues. PMID:27506082

  14. Detection of orally administered inositol stereoisomers in mouse blood plasma and their effects on translocation of glucose transporter 4 in skeletal muscle cells.

    PubMed

    Yamashita, Yoko; Yamaoka, Masaru; Hasunuma, Tomohisa; Ashida, Hitoshi; Yoshida, Ken-ichi

    2013-05-22

    Simple pharmacological studies on inositol stereoisomers are presented in this study. Male ICR mice were orally administered 1 g/kg BW of three inositol stereoisomers, myo-inositol (MI), d-chiro-inositol (DCI), and scyllo-inositol (SI), and blood plasma samples and skeletal muscle fractions were prepared after an hour. The plasma samples were subjected to gas chromatography-coupled time-of-flight mass spectrometry (GC-TOF-MS) analysis. None of the three stereoisomers was seen in untreated samples, but substantial amounts ranging from 2.5 to 6.5 mM were detected only after administration, indicating that orally administered inositol stereoisomers were readily absorbed and their levels elevated in the bloodstream. In addition, plasma of SI-administered animals contained substantial MI, suggesting a possible metabolic conversion of SI to MI. In the skeletal muscle fractions, glucose transporter type 4 (GLUT4) content in the plasma membrane increased, indicating that inositol stereoisomers stimulated GLUT4 translocation.

  15. Antiviral Characteristics of GSK1265744, an HIV Integrase Inhibitor Dosed Orally or by Long-Acting Injection

    PubMed Central

    Kobayashi, Masanori; Seki, Takahiro; Miki, Shigeru; Wakasa-Morimoto, Chiaki; Suyama-Kagitani, Akemi; Kawauchi-Miki, Shinobu; Taishi, Teruhiko; Kawasuji, Takashi; Johns, Brian A.; Underwood, Mark R.; Garvey, Edward P.; Sato, Akihiko; Fujiwara, Tamio

    2014-01-01

    GSK1265744 is a new HIV integrase strand transfer inhibitor (INSTI) engineered to deliver efficient antiviral activity with a once-daily, low-milligram dose that does not require a pharmacokinetic booster. The in vitro antiviral profile and mechanism of action of GSK1265744 were established through integrase enzyme assays, resistance passage experiments, and cellular assays with site-directed molecular (SDM) HIV clones resistant to other classes of anti-HIV-1 agents and earlier INSTIs. GSK1265744 inhibited HIV replication with low or subnanomolar efficacy and with a selectivity index of at least 22,000 under the same culture conditions. The protein-adjusted half-maximal inhibitory concentration (PA-EC50) extrapolated to 100% human serum was 102 nM. When the virus was passaged in the presence of GSK1265744, highly resistant mutants with more than a 10-fold change (FC) in EC50 relative to that of the wild-type were not observed for up to 112 days of culture. GSK1265744 demonstrated activity against SDM clones containing the raltegravir (RAL)-resistant Y143R, Q148K, N155H, and G140S/Q148H signature variants (FC less than 6.1), while these mutants had a high FC in the EC50 for RAL (11 to >130). Either additive or synergistic effects were observed when GSK1265744 was tested in combination with representative anti-HIV agents, and no antagonistic effects were seen. These findings demonstrate that, similar to dolutegravir, GSK1265744 is differentiated as a new INSTI, having a markedly distinct resistance profile compared with earlier INSTIs, RAL, and elvitegravir (EVG). The collective data set supports further clinical development of GSK1265744. PMID:25367908

  16. Relapse Prevention in Schizophrenia and Schizoaffective Disorder with Risperidone Long-Acting Injectable vs Quetiapine: Results of a Long-Term, Open-Label, Randomized Clinical Trial

    PubMed Central

    Gaebel, Wolfgang; Schreiner, Andreas; Bergmans, Paul; de Arce, Rosario; Rouillon, Frédéric; Cordes, Joachim; Eriksson, Lars; Smeraldi, Enrico

    2010-01-01

    Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse. An open-label, randomized, active-controlled, 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone, olanzapine, or conventional neuroleptics to risperidone long-acting injectable (RLAI) or oral quetiapine. Primary effectiveness evaluation was time-to-relapse. Safety evaluations included adverse events (AEs) reported for the duration of the study, Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, and vital signs. A total of 666 patients (n=329 RLAI, n=337 quetiapine) were evaluable for effectiveness measures. Baseline demographics were similar between treatment groups. Kaplan–Meier estimate of time-to-relapse was significantly longer with RLAI (p<0.0001). Relapse occurred in 16.5% of patients with RLAI and 31.3% with quetiapine. RLAI and quetiapine were both safe and well tolerated. Weight gain affected 7% of patients with RLAI and 6% with quetiapine, with mean end point increases of 1.25±6.61 and 0±6.55 kg, respectively. There were no significant between-group differences in weight gain. ESRS total scores decreased similarly after randomization to either RLAI or quetiapine. Extrapyramidal AEs occurred in 10% of patients with RLAI and 6% with quetiapine. Treatment-emergent potentially prolactin-related AEs were reported in 15 (5%) patients with RLAI and 5 (2%) patients with quetiapine; hyperprolactinemia was reported in 43 (13.1%) patients with RLAI and 5 (1.5%) patients with quetiapine. Somnolence occurred in 2% of patients with RLAI and 11% with quetiapine. To our knowledge, this is the first report of a randomized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy. Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was

  17. “Set it and forget it”: Women’s perceptions and opinions of long-acting topical vaginal gels

    PubMed Central

    van den Berg, Jacob J.; Rosen, Rochelle K.; Bregman, Dana E.; Thompson, Lara A.; Jensen, Kathleen M.; Kiser, Patrick F.; Katz, David F.; Buckheit, Karen; Buckheit, Robert W.; Morrow, Kathleen M.

    2014-01-01

    Women’s initial understandings and anticipated acceptability of long-acting vaginal gels as potential anti-HIV microbicides was investigated by exploring the perceptibility variables associated with prototype formulations. Four focus groups with 29 women, aged 18–45, were conducted to consider gel prototypes with varied physicochemical and rheological properties. Participants responded favorably to the concept of long-acting vaginal gels as microbicides. Distinctions in understandings and stated needs regarding product dosing, characteristics, and effectiveness offer valuable insights into product design. Long-acting vaginal gels capable of protecting against HIV/STIs will be a viable option among potential users, with dosing frequency being an important factor in willingness to use. PMID:24248674

  18. A randomised trial comparing the efficacy and safety of topical ketoprofen in Transfersome(®) gel (IDEA-033) with oral ketoprofen and drug-free ultra-deformable Sequessome™ vesicles (TDT 064) for the treatment of muscle soreness following exercise.

    PubMed

    Seidel, Egbert J; Rother, Matthias; Regenspurger, Katja; Rother, Ilka

    2016-01-01

    We compared the effectiveness of topical ketoprofen in Transfersome(®) gel (IDEA-033) with oral ketoprofen and drug-free Sequessome™ vesicles (FLEXISEQ(®) Sport; TDT 064) in reducing calf muscle soreness. One hundred and sixty eight healthy individuals with a pain score ≥ 3 (10-point scale) 12-16 h post-exercise (walking down stairs with an altitude of 300-400 m) were randomised to receive IDEA-033 plus oral placebo (two dose groups), oral ketoprofen plus TDT 064, or TDT 064 plus oral placebo. The primary endpoint was muscle soreness reduction from pre-dosing to Day 7. Higher pain scores were recorded with oral ketoprofen plus TDT 064 (mean ± s 462.4 ± 160.4) versus IDEA-033 plus oral placebo (434.7 ± 190.8; P = 0.2931) or TDT 064 plus oral placebo (376.2 ± 159.1; P = 0.0240) in the 7 days post-exercise. Recovery from muscle soreness was longer with oral ketoprofen plus TDT 064 (mean 91.0 ± 19.5 h) versus IDEA-033 plus placebo (mean 81.4 ± 22.9 h; P = 0.5964) or TDT 064 plus placebo (mean 78.9 ± 22.8 h; P = 0.0262). In conclusion, ultradeformable phospholipid vesicles ± ketoprofen did not retard recovery from muscle soreness. TDT 064 improves osteoarthritis-related pain and could be of interest as a treatment for joint pain during and post-exercise.

  19. Development and comparison of intramuscularly long-acting paliperidone palmitate nanosuspensions with different particle size.

    PubMed

    Leng, Donglei; Chen, Hongming; Li, Guangjing; Guo, Mengran; Zhu, Zhaolu; Xu, Lu; Wang, Yongjun

    2014-09-10

    The main purpose of this study was to develop and compare the pharmacokinetic behavior of two paliperidone palmitate (PP) nanosuspensions with different particle size after intramuscular (i.m.) administration. PP nanosuspensions were prepared by wet media milling method and the mean particle size of nanosuspension was controlled as 1,041 ± 6 nm (A) and 505 ± 9 nm (B), respectively. The morphology of nanosuspensions was observed by scanning electron microscope (SEM). Differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD) confirmed the crystallinity of PP in nanosuspensions. The physical and chemical stabilities of nanosuspensions A and B were investigated by particle analyzer and HPLC after storage for 2 months at 25°C, 4°C and mechanical shaking condition. No obvious change in particle size and chemical degradation of drug were observed. Following single-dose i.m. administration to beagle dogs, the release of paliperidone lasted for nearly 1 month. The Tmax of nanosuspensions A and B was 6 (d) and 10 (d). The AUC0-t and Cmax of nanosuspensions A was 2.0-fold and 1.8-fold higher than nanosuspensions B (p<0.05). The results demonstrated that PP nanosuspensions formulation had long-acting effect. Nanosuspension A with a larger particle size performed better than nanosuspension B. As a result, it is important to design appropriate particle size of nanosuspensions for i.m. administration in order to produce larger therapeutic effect.

  20. Permanent Sterilisation to Long-Acting Reversible Contraception: Is a Paradigm Shift Necessary?

    PubMed

    Shantha Kumari, S

    2016-06-01

    The concept of family planning originated as birth control in 1912 to control the size of the family and prevent unplanned pregnancies transformed to family welfare and later on expanded its horizons to reproductive and child health (RCH). A wide spectrum of choices both for male and female, temporary and permanent, have been developed and offered. Developed world having stabilised population faces problem with teenage and adolescent pregnancies. Developing nations are still struggling to stabilise population and traditionally depend on permanent female sterilisation as a major method of contraception. Lot of unmet need is seen in young recently married women, post-delivery, post-abortal states. Long-acting reversible contraception which includes intrauterine device, IUD, and implants has re-emerged strongly as a first choice of contraception for women of all ages including unmarried teenage pregnancies. They are highly efficient with failure rates equivalent or better than permanent methods, cost-effective, reversible, and have the potential to replace permanent sterilisation. PMID:27298522

  1. The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge.

    PubMed

    Radzio, Jessica; Spreen, William; Yueh, Yun Lan; Mitchell, James; Jenkins, Leecresia; García-Lerma, J Gerardo; Heneine, Walid

    2015-01-14

    Daily preexposure prophylaxis (PrEP) with Truvada is a proven HIV prevention strategy; however, its effectiveness is limited by low adherence. Antiretroviral drug formulations that require infrequent dosing may increase adherence and thus PrEP effectiveness. We investigated whether monthly injections of a long-acting formulation of the HIV integrase inhibitor GSK1265744 (GSK744 LA) prevented simian/human immunodeficiency virus (SHIV) infection by vaginal challenge in macaques. Female pigtail macaques (n = 12) were exposed to intravaginal inoculations of SHIV twice a week for up to 11 weeks. Half of the animals received a GSK744 LA injection every 4 weeks, and half received placebo. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all six macaques from infection. Placebo controls were all infected after a median of 4 (range, 2 to 20) vaginal challenges with SHIV. Efficacy was related to high and sustained vaginal and plasma drug concentrations that remained above the protein-adjusted 90% inhibitory concentration during the dosing cycles. These data support advancement of GSK744 LA as a potential PrEP candidate for women. PMID:25589631

  2. Demand for long-acting and permanent contraceptive methods among Kurdish women in Mahabad, Iran.

    PubMed

    Hosseini, Hatam; Torabi, Fatemeh; Bagi, Balal

    2014-11-01

    It is anticipated that the demand for contraceptives in Iran will increase in the near future as the number of women of reproductive age increases and with women wanting smaller families. The aim of this paper was to study the demand for long-acting and permanent contraceptive methods (LAPCMs), and its determinants, among Kurdish women in Mahabad city, Iran. Data were taken from the Mahabad Fertility Survey (MFS) conducted on a sample of over 700 households in April 2012. The results show that the demand for LAPCMs was 71.35% at the time of survey, although only 27.7% of women were using these methods. Thus, the number of unintended pregnancies is likely to increase in the future if this gap is not reduced. The multivariate analysis showed significant impacts on the dependent variables of the number of children ever born, perceived contraceptive costs and childbearing intentions. Moreover, women at the end of their reproductive lives and those with higher education were more likely to desire LAPCMs. It is concluded that despite a growing use of contraceptive methods in Iran in recent decades, the development of reproductive health services and promotion of the quality of family planning services remains a necessity.

  3. Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.

    PubMed

    McCue, Justin; Kshirsagar, Rashmi; Selvitelli, Keith; Lu, Qi; Zhang, Mingxuan; Mei, Baisong; Peters, Robert; Pierce, Glenn F; Dumont, Jennifer; Raso, Stephen; Reichert, Heidi

    2015-07-01

    Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8-15 log10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc.

  4. Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir boosted atazanavir nanoformulations

    PubMed Central

    Puligujja, Pavan; Balkundi, Shantanu; Kendrick, Lindsey; Baldridge, Hannah; Hilaire, James; Bade, Aditya N.; Dash, Prasanta K.; Zhang, Gang; Poluektova, Larisa; Gorantla, Santhi; Liu, Xin-Ming; Ying, Tianlei; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S.; McMillan, JoEllyn M.; Gendelman, Howard E.

    2014-01-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) that target monocyte-macrophage could improve the drug’s half-life and protein binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly affected several therapeutic factors: drug bioavailability increased as much as 5 times and PD activity improved as much as 100 times. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice and infected with HIV-1ADA at a tissue culture infective dose50 of 104 infectious viral particles/ml led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitate drug carriage and facilitate antiretroviral responses. PMID:25522973

  5. Pharmacokinetics of a long-acting chloramphenicol formulation administered by intramuscular and subcutaneous routes in cattle.

    PubMed

    Sanders, P; Guillot, P; Mourot, D

    1988-06-01

    The pharmacokinetic properties of a long-acting formulation of chloramphenicol were determined in six yearling cattle after a single intravenous (i.v.) administration (40 mg/kg body weight) and after two sequential subcutaneous (s.c.) or intramuscular (i.m.) administrations (90 mg/kg/48 h). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. Mean values were a half-life of 4.1 h, a volume of distribution of 0.86 l/kg and a body clearance of 0.128 l/kg/h. Plasma concentrations of chloramphenicol following i.m. and s.c. administrations increased slowly to a broad peak at 10-15 micrograms/ml between 9 and 12 h. Bioavailability was 19.1% after i.m. injection and 12.4% after s.c. administration. The extent of absorption from the two routes did not differ significantly. The rate of absorption was significantly lower after s.c. application than it was after i.m. injection. The time necessary for the plasma concentration to exceed 5 micrograms/ml was the same for the two routes. Thus, i.m. and s.c. routes are bioequivalent.

  6. Subcutaneously Administered Self-Cleaving Hydrogel-Octreotide Conjugates Provide Very Long-Acting Octreotide.

    PubMed

    Schneider, Eric L; Henise, Jeff; Reid, Ralph; Ashley, Gary W; Santi, Daniel V

    2016-07-20

    We developed a long-acting drug-delivery system that supports subcutaneous administration of the peptidic somatostatin agonist octreotide-a blockbuster drug used to treat acromegaly and neuroendocrine tumors. The current once-a-month polymer-encapsulated octreotide, Sandostatin LAR, requires a painful intragluteal injection through a large needle by a health-care professional. To overcome such shortcomings, Tetra-PEG hydrogel microspheres were covalently attached to the α-amine of d-Phe(1) or the ε-amine of Lys(5) of octreotide by a self-cleaving β-eliminative linker; upon subcutaneous injection in the rat using a small-bore needle, octreotide was slowly released. The released drug from the ε-octreotide conjugate showed a remarkably long serum half-life that exceeded two months. The α-octreotide conjugate had a half-life of ∼2 weeks, and showed an excellent correlation of in vitro and in vivo drug release. Pharmacokinetic models indicate these microspheres should support once-weekly to once-monthly self-administered subcutaneous dosing in humans. The hydrogel-octreotide conjugate shows the favorable pharmacokinetics of Sandostatin LAR without its drawbacks. PMID:27253622

  7. A long-acting cholinesterase inhibitor reverses spatial memory deficits in mice.

    PubMed

    Sweeney, J E; Höhmann, C F; Moran, T H; Coyle, J T

    1988-09-01

    The effects of the long-acting acetylcholinesterase (AChE) inhibitor, galanthamine, on spatial memory were investigated in mice. Mice received ibotenic acid or sham lesions to the nucleus basalis magnocellularis (nBM). Groups of nBM-lesioned and control mice were then trained on a modified Morris swim maze task. Each mouse was first placed on a platform and then into quadrants of the swim tank in a random order. Time required to find the hidden platform was measured. In different phases of testing, the animal had to find a platform that either remained in the same quadrant (reference memory component) or was moved daily (working memory component). The nBM-lesioned mice took significantly longer to find the platform as compared to controls on the working, but not on the reference, memory component of the task. Galanthamine (5.0 mg/kg, IP), given 3.5 hours before testing, improved performance on the working memory task in nBM-lesioned mice by 70% and strikingly impaired performance in controls. Galanthamine's ability to reverse cognitive deficits induced by nBM lesions and its comparatively long half-life suggest that it may be effective in treating the central cholinergic deficits in Alzheimer's disease patients.

  8. Contraception for Adolescents: Focusing on Long-Acting Reversible Contraceptives (LARC) to Improve Reproductive Health Outcomes

    PubMed Central

    Salcedo, Jennifer

    2015-01-01

    Adolescent pregnancy rates in the U.S. have reached an all-time low from their peak in the 1980s and 1990s. However, the U.S. maintains the highest rate of teenage pregnancy among developed nations. Adolescents experience higher typical use failure rates for user-dependent contraceptives compared to their adult counterparts. Long-acting reversible contraception (LARC), IUDs and implants, have failure rates that are both very low and independent of user age. In settings where the most effective methods are prioritized and access barriers are removed, the majority of adolescents initiate LARC. Use of LARC by adolescents significantly reduces rates of overall and repeat teen pregnancy. All methods of contraception are safe for use in teens, including IUDs and DMPA. Dual use of LARC and barrier methods to reduce risk of sexually transmitted infection, is the optimal contraceptive strategy for most adolescents. Adolescent access to evidence-based and confidential contraceptive services, provided in a manner that respects autonomy, is a vital public health goal.

  9. Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma.

    PubMed

    Xia, Ying; Kelton, Christina M L; Xue, Liang; Guo, Jeff J; Bian, Boyang; Wigle, Patricia R

    2013-12-01

    The introduction of long-acting beta agonists (LABAs) was considered a major advance in bronchodilator therapy for adult, as well as pediatric, patients with asthma. However, the use of LABAs has raised safety concerns, especially the potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone in the treatment of mild-to-severe persistent asthma, has been associated with growth suppression in children. The purpose of this review was to identify and discuss the major published safety studies surrounding LABA, ICS, and combined LABA/ICS usage in children. By way of a critical search for influential published clinical trials, meta-analyses, and observational studies, six studies relevant to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and four studies on the subject of LABA/ICS combination usage were identified and reviewed. Based on the reviewed literature, the controversy surrounding these anti-asthma medications was clearly exposed. On the one hand, there is some evidence that LABA monotherapy may be associated with SAEs and asthma-related death, while ICS monotherapy may be associated with a higher risk of growth suppression. On the other hand, the concurrent use of a LABA with an ICS has been associated with positive outcomes including symptom reduction and reduced rate and severity of exacerbations. Further clinical research is warranted and has been called for by the US Food and Drug Administration. PMID:25114786

  10. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    PubMed Central

    Guarnieri, Michael; Tyler, Betty M.; DeTolla, Louis; Zhao, Ming; Kobrin, Barry

    2014-01-01

    Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs. PMID:24459402

  11. Contraceptive implants: long acting and provider dependent contraception raises concerns about freedom of choice.

    PubMed Central

    Thompson, M. S.

    1996-01-01

    David Bromham's editorial on contraceptive implants ignores the wider issues to voice concern that trial by media could limit contraceptive choice by jeopardising research into new methods. However, it is more beneficial to the public for points of conflict to be debated openly. Furthermore, the impetus for research into new contraceptive technology is driven by profit and political motives and is only marginally affected by the media. Implanted contraceptives may increase the choice of contraceptive methods, but they put control of fertility increasingly into the hands of the medical profession. Herein lies their greatest problem: their potential to increase providers' control over clients' choice. There is the danger that certain groups of women may be targeted for their use: in the United States the coercive use of Norplant for mothers receiving welfare benefit has been suggested. Long acting contraceptives are a contraceptive of choice only when they are available without pressure, as part of a wider menu; when instant removal on request is guaranteed; and when there is an open and free flow of information and opinions between users, health professionals, and special interest groups. Images p1394-a PMID:8956712

  12. Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma

    PubMed Central

    Xia, Ying; Kelton, Christina M. L.; Xue, Liang; Bian, Boyang; Wigle, Patricia R.

    2013-01-01

    The introduction of long-acting beta agonists (LABAs) was considered a major advance in bronchodilator therapy for adult, as well as pediatric, patients with asthma. However, the use of LABAs has raised safety concerns, especially the potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone in the treatment of mild-to-severe persistent asthma, has been associated with growth suppression in children. The purpose of this review was to identify and discuss the major published safety studies surrounding LABA, ICS, and combined LABA/ICS usage in children. By way of a critical search for influential published clinical trials, meta-analyses, and observational studies, six studies relevant to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and four studies on the subject of LABA/ICS combination usage were identified and reviewed. Based on the reviewed literature, the controversy surrounding these anti-asthma medications was clearly exposed. On the one hand, there is some evidence that LABA monotherapy may be associated with SAEs and asthma-related death, while ICS monotherapy may be associated with a higher risk of growth suppression. On the other hand, the concurrent use of a LABA with an ICS has been associated with positive outcomes including symptom reduction and reduced rate and severity of exacerbations. Further clinical research is warranted and has been called for by the US Food and Drug Administration. PMID:25114786

  13. Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases

    PubMed Central

    Palot, Alain; Sofalvi, Tunde; Pahus, Laurie; Gouitaa, Marion; Tummino, Celine; Martinez, Stephanie; Charpin, Denis; Bourdin, Arnaud; Chanez, Pascal

    2014-01-01

    Acetylcholine (neuronal and non-neuronal origin) regulates bronchoconstriction, and mucus secretion. It has an inflammatory effect by inducing attraction, survival and cytokine release from inflammatory cells. Muscarinic receptors throughout the bronchial tree are mainly restricted to muscarinic M1, M2 and M3 receptors. Three long-acting muscarinic receptor antagonists (LAMAs) were approved for the treatment of chronic obstructive pulmonary disease (COPD) in Europe: once-daily tiotropium bromide; once-daily glycopyrronium bromide; and twice-daily aclidinium bromide. All have higher selectivity for M3 receptors than for M2 receptors, and dissociate more slowly from the M3 receptors than they do from the M2 receptors. Some LAMAs showed anti-inflammatory effects [inhibition of neutrophil chemotactic activity and migration of alveolar neutrophils, decrease of several cytokines in the bronchoalveolar lavage (BAL) including interleukin (IL)-6, tumor necrosis factor (TNF)-α and leukotriene (LT)B4] and antiremodeling effects (inhibition of mucus gland hypertrophy and decrease in MUC5AC-positive goblet cell number, decrease in MUC5AC overexpression). In the clinic, LAMAs showed a significant improvement of forced expiratory volume in 1 second (FEV1), quality of life, dyspnea and reduced the number of exacerbations in COPD and more recently in asthma. This review will focus on the three LAMAs approved in Europe in the treatment of chronic airway diseases. PMID:24587893

  14. Contraception for Adolescents: Focusing on Long-Acting Reversible Contraceptives (LARC) to Improve Reproductive Health Outcomes

    PubMed Central

    Salcedo, Jennifer

    2015-01-01

    Adolescent pregnancy rates in the U.S. have reached an all-time low from their peak in the 1980s and 1990s. However, the U.S. maintains the highest rate of teenage pregnancy among developed nations. Adolescents experience higher typical use failure rates for user-dependent contraceptives compared to their adult counterparts. Long-acting reversible contraception (LARC), IUDs and implants, have failure rates that are both very low and independent of user age. In settings where the most effective methods are prioritized and access barriers are removed, the majority of adolescents initiate LARC. Use of LARC by adolescents significantly reduces rates of overall and repeat teen pregnancy. All methods of contraception are safe for use in teens, including IUDs and DMPA. Dual use of LARC and barrier methods to reduce risk of sexually transmitted infection, is the optimal contraceptive strategy for most adolescents. Adolescent access to evidence-based and confidential contraceptive services, provided in a manner that respects autonomy, is a vital public health goal. PMID:27635305

  15. Global trends in use of long-acting reversible and permanent methods of contraception: Seeking a balance.

    PubMed

    Joshi, Ritu; Khadilkar, Suvarna; Patel, Madhuri

    2015-10-01

    The global trend shows that the use of permanent contraception to prevent unintended pregnancy is high. Although the trend also shows a rise in the use of long-acting reversible methods, these are still underutilized despite having contraceptive as well as non-contraceptive benefits. Lack of knowledge among women, dependence on the provider for information, and provider bias for permanent contraception are cited as reasons for this reduced uptake. Training of healthcare providers and increased patient awareness about the effectiveness of long-acting reversible contraceptive methods will increase their uptake and help prevent unintended pregnancies.

  16. Marker residue determination of tritium-labeled ivermectin in the muscle of aquacultured largemouth bass, hybrid striped bass, and yellow perch following oral treatment.

    PubMed

    Shaikh, Badar; Rummel, Nathan; Yu, Donglei; Gieseker, Charles; Evans, Eric; Hasbrouck, Nicholas; Reimschuessel, Renate

    2012-05-01

    The residue depletion profiles of tritium-labeled ivermectin and its metabolites in the muscle of aquacultured largemouth bass (LMB), hybrid striped bass (HSB), and yellow perch (YP) following oral treatment are reported. Fish were administered ³H-ivermectin at the dose level of 0.1 mg/kg body weight (7-9 μCi) in a gel capsule via stomach tube. At each postdose withdrawal time, six fish of each species were sedated with buffered MS-222 and blood samples taken. Fish were then euthanized, and fillets with adhering skin (scales removed) and bile samples were collected. The muscle fillets were homogenized in dry ice to a fine powder. Aliquots of tissue, plasma, and bile were assayed for total radioactive residue (TRR). The homogenized muscle was extracted in acetonitrile or methanol followed by high-performance liquid chromatographic (HPLC) analysis to determine the presence of parent ivermectin and its potential metabolites. The highest TRR concentrations (ivermectin equivalents) of 53, 45, and 44 ng/g (ppb) were obtained on postdose day 1 for HSB, LMB, and YP, respectively. The TRR depleted most slowly in HSB to 25 ppb at day 91, followed by YP to 19 ppb at day 42 and then by LMB to 22 ppb at day 35. The total residue of ivermectin and its metabolites by HPLC analysis followed the same depletion pattern in the three species. Additionally, the depletion rate of TRR of ³H-ivermectin in the three species followed the pattern bile > plasma > muscle. The results further indicate that one of the polar metabolites of ivermectin could serve as a potential marker residue as an indication of use, rather than the parent ivermectin. PMID:22452736

  17. Marker residue determination of tritium-labeled ivermectin in the muscle of aquacultured largemouth bass, hybrid striped bass, and yellow perch following oral treatment.

    PubMed

    Shaikh, Badar; Rummel, Nathan; Yu, Donglei; Gieseker, Charles; Evans, Eric; Hasbrouck, Nicholas; Reimschuessel, Renate

    2012-05-01

    The residue depletion profiles of tritium-labeled ivermectin and its metabolites in the muscle of aquacultured largemouth bass (LMB), hybrid striped bass (HSB), and yellow perch (YP) following oral treatment are reported. Fish were administered ³H-ivermectin at the dose level of 0.1 mg/kg body weight (7-9 μCi) in a gel capsule via stomach tube. At each postdose withdrawal time, six fish of each species were sedated with buffered MS-222 and blood samples taken. Fish were then euthanized, and fillets with adhering skin (scales removed) and bile samples were collected. The muscle fillets were homogenized in dry ice to a fine powder. Aliquots of tissue, plasma, and bile were assayed for total radioactive residue (TRR). The homogenized muscle was extracted in acetonitrile or methanol followed by high-performance liquid chromatographic (HPLC) analysis to determine the presence of parent ivermectin and its potential metabolites. The highest TRR concentrations (ivermectin equivalents) of 53, 45, and 44 ng/g (ppb) were obtained on postdose day 1 for HSB, LMB, and YP, respectively. The TRR depleted most slowly in HSB to 25 ppb at day 91, followed by YP to 19 ppb at day 42 and then by LMB to 22 ppb at day 35. The total residue of ivermectin and its metabolites by HPLC analysis followed the same depletion pattern in the three species. Additionally, the depletion rate of TRR of ³H-ivermectin in the three species followed the pattern bile > plasma > muscle. The results further indicate that one of the polar metabolites of ivermectin could serve as a potential marker residue as an indication of use, rather than the parent ivermectin.

  18. Neck muscle atrophy and soft-tissue fibrosis after neck dissection and postoperative radiotherapy for oral cancer

    PubMed Central

    Kim, Jinu; Shin, Eun Seow; Kim, Jeong Eon; Yoon, Sang Pil

    2015-01-01

    Late complications of head and neck cancer survivors include neck muscle atrophy and soft-tissue fibrosis. We present an autopsy case of neck muscle atrophy and soft-tissue fibrosis (sternocleidomastoid, omohyoid, digastric, sternohyoid, sternothyroid, and platysma muscles) within the radiation field after modified radical neck dissection type I and postoperative radiotherapy for floor of mouth cancer. A 70-year-old man underwent primary tumor resection of the left floor of mouth, left marginal mandibulectomy, left modified radical neck dissection type I, and reconstruction with a radial forearm free flap. The patient received adjuvant radiotherapy. The dose to the primary tumor bed and involved neck nodes was 63 Gy in 35 fractions over 7 weeks. Areas of subclinical disease (left lower neck) received 50 Gy in 25 fractions over 5 weeks. Adjuvant chemotherapy was not administered. PMID:26756035

  19. A prospective trial of customized adherence enhancement plus long-acting injectable antipsychotic medication in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder

    PubMed Central

    Sajatovic, Martha; Levin, Jennifer; Ramirez, Luis F.; Hahn, David Y.; Tatsuoka, Curtis; Bialko, Christopher S.; Cassidy, Kristin A.; Fuentes-Casiano, Edna; Williams, Tiffany D.

    2014-01-01

    Background Treatment non-adherence in people with schizophrenia is associated with relapse and homelessness. Building upon the usefulness of long-acting medication, and our work in psychosocial interventions to enhance adherence, we conducted a prospective uncontrolled trial of customized adherence enhancement (CAE) plus long-acting injectable antipsychotic (LAI) using haloperidol decanoate in 30 homeless or recently homeless individuals with schizophrenia and schizoaffective disorder. Methods Participants received monthly CAE and LAI (CAE-L) for 6 months. Primary outcomes were adherence as measured by the Tablets Routine Questionnaire (TRQ) and housing status. Secondary outcomes included psychiatric symptoms, functioning, side effects, and hospitalizations. Results Mean age of participants was 41.8 years (SD 8.6), mainly minorities (90% African-American) and mainly single/never married (70%). Most (97%) had past or current substance abuse, and had been incarcerated (97%). Ten individuals (33%) terminated the study prematurely. CAE-L was associated with good adherence to LAI (76% at 6 months) and dramatic improvement in oral medication adherence, which changed from missing 46% of medication at study enrollment to missing only 10% at study end (p = 0.03). There were significant improvements in psychiatric symptoms (p<.001) and functioning (p<.001). Akathisia was a major side effect with LAI. Conclusion While interpretation of findings must be tempered by the methodological limitations, CAE-L appears to be associated with improved adherence, symptoms, and functioning in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder. Additional research is needed on effective and practical approaches to improving health outcomes for homeless people with serious mental illness. PMID:24434094

  20. Differential dose response of mTOR signaling to oral administration of leucine in skeletal muscle and liver of rats.

    PubMed

    Yoshizawa, Fumiaki; Mochizuki, Shinji; Sugahara, Kunio

    2013-01-01

    Phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and 70-kDa ribosomal protein S6 kinase (S6K1) in the rat liver increased in proportion to the amount of leucine administered, ranging from 0.169 to 1.35 g/kg of body weight. In the skeletal muscle, phosphorylation of these factors reached a plateau at 0.675 g/kg of body weight. The sensitivity of mammalian target of rapamycin (mTOR) signaling to leucine in the skeletal muscle appeared to be higher than that in the liver.

  1. Substituting a long-acting dopamine uptake inhibitor for cocaine prevents relapse to cocaine seeking.

    PubMed

    Velázquez-Sánchez, Clara; Ferragud, Antonio; Ramos-Miguel, Alfredo; García-Sevilla, Jesús A; Canales, Juan J

    2013-07-01

    The treatment of cocaine addiction remains a challenge. The dopamine replacement approach in cocaine addiction involves the use of a competing dopaminergic agonist that might suppress withdrawal and drug craving in abstinent individuals. Although it has long been postulated that such an approach may be therapeutically successful, preclinical or clinical evidence showing its effectiveness to prevent relapse is scant. We used in rats a procedure that involved substitution of the N-substituted benztropine analog 3α-[bis(4'-fluorophenyl)methoxy]-tropane (AHN-1055), a long-acting dopamine uptake inhibitor (DUI), for cocaine. Maintenance treatment was self-administered. After extinction, reinstatement of drug seeking was induced by cocaine priming. We measured the contents of brain-derived neurotrophic factor (BDNF), c-Fos and Fas-associated death domain (FADD) proteins in the medial prefrontal cortex (mPFC) following reinstatement. DUI, but not amphetamine, substitution led to extinction of active lever presses, as did saline substitution. DUI substitution significantly reduced cocaine-induced reinstatement of drug-seeking behavior, which was strongly elicited after saline substitution. Rats passively yoked to DUI also showed reduced cocaine-primed reinstatement. Reductions in drug seeking during reinstatement were matched by downward shifts in the contents of BDNF, c-Fos and FADD proteins in the mPFC, which were elevated in relapsing rats. These data indicate that DUI substitution not only leads to extinction of self-administration behavior but also prevents reinstatement of drug seeking induced by cocaine re-exposure. Thus, DUI substitution therapy using compounds with low abuse potential, even if received passively in the context previously paired with drug taking, may provide an effective treatment for stimulant addiction.

  2. Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD

    PubMed Central

    Pavord, Ian D; Lettis, Sally; Locantore, Nicholas; Pascoe, Steve; Jones, Paul W; Wedzicha, Jadwiga A; Barnes, Neil C

    2016-01-01

    Objective We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy. Methods Three studies of ≥1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%). At baseline, 57–75% of patients had ≥2% blood eosinophils. Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level. Results For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ. Discussion Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. PMID:26585525

  3. Long-acting Reversible Contraception for Adolescents and Young Adults: Patient and Provider Perspectives

    PubMed Central

    Kavanaugh, Megan L.; Frohwirth, Lori; Jerman, Jenna; Popkin, Ronna; Ethier, Kathleen

    2013-01-01

    Study objective To describe and explore provider- and patient-level perspectives regarding long-acting reversible contraception (LARC) for teens and young adults (ages 16-24). Methods Data collection occurred between June – December 2011. We first conducted telephone interviews with administrative directors at 20 publicly funded facilities that provide family planning services. At six of these sites, we conducted a total of six focus group discussions (FGDs) with facility staff and forty-eight in-depth interviews (IDIs) with facility clients ages 16-24. Results Staff in the FGDs did not generally equate being a teen with ineligibility for IUDs. In contrast to staff, one quarter of the young women did perceive young age as rendering them ineligible. Clients and staff agreed that the “forgettable” nature of the methods and their duration were some of LARC’s most significant advantages. They also agreed that fear of pain associated with both insertion and removal and negative side effects were disadvantages. Some aspects of IUDs and implants were perceived as advantages by some clients but disadvantages by others. Common challenges to providing LARC-specific services to younger patients included extra time required to counsel young patients about LARC methods, outdated clinic policies requiring multiple visits to obtain IUDs, and a perceived higher removal rate among young women. The most commonly cited strategy for addressing many of these challenges was securing supplementary funding to support the provision of these services to young patients. Conclusion Incorporating young women’s perspectives on LARC methods into publicly funded family planning facilities’ efforts to provide these methods to a younger population may increase their use among young women. PMID:23287602

  4. Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors

    PubMed Central

    Cives, M; Kunz, P L; Morse, B; Coppola, D; Schell, M J; Campos, T; Nguyen, P T; Nandoskar, P; Khandelwal, V; Strosberg, J R

    2015-01-01

    Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5 expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5 expression is a potentially predictive biomarker for response. PMID:25376618

  5. Efficacy and safety of conventional long acting β2- agonists: systematic review and meta-analysis

    PubMed Central

    Karbasi-Afshar, Reza; Aslani, Jafar; Ghanei, Mostafa

    2016-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is usually considered one of the leading causes of death worldwide, so finding proper therapeutic strategies for this disease is of high importance. In this meta-analysis, we reviewed the existing literature on the efficacy and safety of conventional long acting beta agonists (LABAs) in COPD patients. Methods: We searched MEDLINE and Google scholar to identify relevant articles. We limited data to double-blinded randomized controlled trials (RCTs). Data of 14, 832 COPD subjects including 7540 patients under a β2 agonist (cases) and 7292 taking placebo (controls) retrieved from 20 randomized controlled trials and were enrolled into this meta-analysis. Evaluated outcomes included overall mortality, exacerbations and tolerance to the drug. Results: The analysis of survival showed no significant difference between those taking LABAs or placebo (relative risk (RR): 0.945, 95% confidence interval (CI): 0.821-1.088, P=0.432). Exacerbation rate, however, was significantly lower among the cases than among the controls (RR: 0.859, 95%CI: 0.800-0.922, p<0.001). Similar observation was detected in analyzing the rate of drug withdrawal in patients of the two groups with patients under placebo having significantly higher rate of drug discontinuation due to adverse events or disease symptoms (RR:0.821, 95% CI: 0.774-0.871; p<0.007). Conclusion: In conclusion, we found that the use of conventional LABA therapy in COPD patients is associated with a lower exacerbation rate of the disease as well as higher tolerance to the drug, but no survival advantage is expectable. Substitution of LABAs with new agents is recommended. PMID:27386055

  6. Who Is Using Long-Acting Reversible Contraceptive Methods? Findings from Nine Low-Fertility Countries

    PubMed Central

    Eeckhaut, Mieke C. W.; Sweeney, Megan M.; Gipson, Jessica D.

    2014-01-01

    CONTEXT Long-acting reversible contraceptive (LARC) methods—IUDs and implants—are more effective than other reversible methods, yet are little used in the United States. Examining which U.S. women use LARC methods and how they differ from users in other low-fertility countries may help point the way toward increasing use. METHODS Data from married or cohabiting women participating in the National Survey of Family Growth (2008–2010) and in eight countries’ Generations and Gender Programme surveys (2004–2010) were used in bivariate and multinomial logistic regression analyses examining LARC use within each setting. RESULTS The proportion of contraceptive use accounted for by LARC methods was generally greater in Europe (10–32%) than in the United States (10%) and Australia (7%). Compared with LARC use among comparable groups in other countries, use was particularly low among U.S. women who were married, were aged 40–44 or had had three or more children, yet was comparatively high among 18–24-year-olds. Among U.S. women, those aged 35–39 or 40–44 were more likely than 18–29-year-olds to rely on sterilization rather than on LARC methods (odds ratios, 3.0 and 10.7, respectively), those who had had three or more children were more likely to do so than were those who had had none or one (4.9), and women who had completed college were less likely than those who had not finished high school to do so (0.4). CONCLUSIONS Certain subgroups of U.S. women may benefit from the reversibility and effectiveness of LARC methods. PMID:25040454

  7. Pharmacokinetics, Pharmacodynamics, and Efficacy of a Novel Long-Acting Human Growth Hormone: Fc Fusion Protein.

    PubMed

    Kim, Su Jin; Kwak, Hyun-Hee; Cho, Sung Yoon; Sohn, Young Bae; Park, Sung Won; Huh, Rimm; Kim, Jinsup; Ko, Ah-Ra; Jin, Dong-Kyu

    2015-10-01

    The current recombinant human growth hormone (rhGH) therapy requires daily subcutaneous (sc) injections, which results in poor patient compliance, especially in young children. To reduce the dosing frequency, we generated a chimeric protein of rhGH and the Fc-domain of immunoglobulin G (IgG) (rhGH-Fc). The pharmacokinetics and pharmacodynamics of sc-injected rhGH-Fc were assessed in male Sprague-Dawley rats and hypophysectomized rats, respectively. A single sc injection of rhGH-Fc at a dose of 0.2 mg/kg slowly reached a Cmax of 16.80 ng/mL and remained for 7 days with a half-life of 51.1 h. Conversely, a single sc injection of rhGH 0.2 mg/kg rapidly reached a Cmax of 46.88 ng/mL and declined with a half-life of 0.55 h to baseline values in 4 h. In the efficacy study, the sc-injected rhGH-Fc induced rapid weight gain and tibial width growth at a dose of 240 μg/animal. The effect of two injections of rhGH-Fc separated by 1 week was comparable to that of the same dose of 14 daily injections of rhGH. The rhGH-Fc is a novel candidate for long-acting rhGH therapy with more convenient weekly administration, as it reduces glomerular filtration and receptor-mediated clearance while allowing for the rapid reversal of potential adverse events.

  8. Liraglutide, a long-acting GLP-1 mimetic, and its metabolite attenuate inflammation after intracerebral hemorrhage

    PubMed Central

    Hou, Jack; Manaenko, Anatol; Hakon, Jakob; Hansen-Schwartz, Jacob; Tang, Jiping; Zhang, John H

    2012-01-01

    The inflammatory response plays a pivotal role in propagating injury of intracerebral hemorrhage (ICH). Glucagon-like-peptide-1 (GLP-1) is a hormone with antidiabetic effect and may also have antiinflammatory properties. Despite consensus that the glucoregulatory action is mediated by the GLP-1 receptor (GLP-1R), mechanisms in the brain remain unclear. We investigated the effect of a long-acting GLP-1 analog, liraglutide, and its truncated metabolite, GLP-1(9-36)a from dipeptidyl peptidase-4 (DPP-4) cleavage in ICH-induced brain injury. Primary outcomes were cerebral edema formation, neurobehavior, and inflammatory parameters. GLP-1(9-36)a, GLP-1R inhibitor, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation inhibitor and DPP-4 inhibitor were administered to examine the mechanisms of action. Liraglutide suppressed neuroinflammation, prevented brain edema and neurologic deficit following ICH, which were partially reversed by GLP-1R inhibitor and AMPK phosphorylation inhibitor. Liraglutide-mediated AMPK phosphorylation was unaffected by GLP-1R inhibitor, and was found to be induced by GLP-1(9-36)a. GLP-1(9-36)a showed salutary effects on primary outcomes that were reversed by AMPK phosphorylation inhibitor but not by GLP-1R inhibitor. Liraglutide and DPP-4 inhibitor co-administration reversed liraglutide-mediated AMPK phosphorylation and antiinflammatory effects. Liraglutide exerted duals actions and the antiinflammatory effects are partially mediated by its metabolite in a phosphorylated AMPK-dependent manner. Therapies that inhibit GLP-1 degradation may weaken the metabolite-mediated effects. PMID:22968320

  9. Efficacy and Safety of Long-Acting Reversible Contraception in Women With Cardiovascular Conditions.

    PubMed

    Vu, Quyen; Micks, Elizabeth; McCoy, Erin; Prager, Sarah

    2016-01-15

    The physiological changes that occur during pregnancy can be deleterious to women with a cardiovascular condition. Evidence-based contraceptive counseling and provision is essential in this patient population. Although long-acting reversible contraception (LARCs), which include the intrauterine device (IUD) and the etonogestrel contraceptive implant, have been found to be safe and effective in healthy women, there are inadequate data regarding LARC use in patients with cardiovascular conditions. We conducted a retrospective chart review of women diagnosed with cardiovascular disease who had a copper IUD, levonorgestrel-releasing intrauterine system or contraceptive implant placed at the University of Washington Medical Center from 2007 to 2012. We abstracted and analyzed patient demographic characteristics, medical conditions, indications for LARC placement, and complications. The sample included 470 women with cardiovascular conditions. The mean age was 34.6 years. One hundred twenty-four patients (26.11%) were nulligravid and 169 patients (35.58%) were nulliparous. Four hundred ten chose the levonorgestrel-releasing intrauterine system (87.23%), 33 patients (7.02%) opted for the copper IUD, and 23 patients (4.89%) chose the etonogestrel implant. Eighteen patients (3.83%) had a confirmed IUD expulsion, 2 patients (0.43%) became pregnant, and there were 4 cases of pelvic inflammatory disease (0.85%). There were no cases of perforation. There were no confirmed cases of infective endocarditis associated with LARC insertion. In conclusion, LARC devices appear safe with few complications for women with cardiovascular conditions. Clinicians can be reassured that LARC may be offered as an appropriate option when counseling women with cardiovascular disease on safe contraceptive methods.

  10. The management of a case of treatment-resistant paraphilia with a long-acting LHRH agonist.

    PubMed

    Dickey, R

    1992-10-01

    A patient with multiple paraphilias who had been treated for several years with sex drive reducing agents (cyproterone acetate and medroxyprogesterone acetate) with little effect on sexual activity or fantasy was offered treatment with long-acting leuprolide acetate, on LHRH agonist. This produced a marked decrease in all reported sexual thoughts and activities with no significant side-effects.

  11. Antipsychotic-induced metabolic effects in the female rat: Direct comparison between long-acting injections of risperidone and olanzapine.

    PubMed

    Ersland, Kari M; Skrede, Silje; Røst, Therese H; Berge, Rolf K; Steen, Vidar M

    2015-12-01

    Several antipsychotics have well-known adverse metabolic effects. Studies uncovering molecular mechanisms of such drugs in patients are challenging due to high dropout rates, previous use of antipsychotics and restricted availability of biological samples. Rat experiments, where previously unexposed animals are treated with antipsychotics, allow for direct comparison of different drugs, but have been hampered by the short half-life of antipsychotics in rodents. The use of long-acting formulations of antipsychotics could significantly increase the value of rodent models in the molecular characterization of therapeutic and adverse effects of these agents. However, as long-acting formulations have rarely been used in rodents, there is a need to characterize the basic metabolic phenotype of different antipsychotics. Using long-acting olanzapine injections as a positive control, the metabolic effects of intramuscular long-acting risperidone in female rats were investigated for the first time. Like olanzapine, risperidone induced rapid, significant hyperphagia and weight gain, with concomitant increase in several plasma lipid species. Both drugs also induced weight-independent upregulation of several genes encoding enzymes involved in lipogenesis, but this activation was not confirmed at the protein level. Our findings shed light on the role of drug administration, drug dose and nutritional status in the development of rodent models for adverse metabolic effects of antipsychotic agents. PMID:26378122

  12. ORAL MYOFUNCTIONAL AND ELECTROMYOGRAPHIC EVALUATION OF THE ORBICULARIS ORIS AND MENTALIS MUSCLES IN PATIENTS WITH CLASS II/1 MALOCCLUSION SUBMITTED TO FIRST PREMOLAR EXTRACTION

    PubMed Central

    de Souza, Denize Ramirez; Semeghini, Tatiana Adamov; Kroll, Lucio Benedito; Berzin, Fausto

    2008-01-01

    Objective: The aim of this study was to assess the presence of oral myofunctional alterations before and after first premolar extraction in Class II/1 malocclusion patients that could endanger the long-term dental arch stability. Material and Methods: The study was performed by means of morphological, functional and electromyographic analyses in 17 Class II/1 malocclusion patients (group T) and 17 Class I malocclusion patients (group C -control), both groups with 12-30-year age range (mean age: 20.93 ± 4.94 years). Results: Data analyzed statistically by Student's t-test showed a significant decrease (p<0.05) in the maxillary and mandibular dental arch perimeters after orthodontic treatment, but lip posture at rest did not present statistically significant differences after treatment (p>0.05). The Kruskal-Wallis test analyzed data from lip posture (orbicularis oris muscle) at rest and during swallowing, as well as the mentalis muscle behavior during the above-mentioned function, not showing statistically significant differences (p>0.05) after treatment (groups T1 and T2). However, group T differed significantly from group C (p<0.05). Lip posture during swallowing showed statistically significant differences (p<0.05) for subjects submitted to orthodontic therapy when compared to data acquired before the treatment. The electromyographic analysis confirmed these data. Conclusions: Found myofunctional alterations observed after the orthodontic treatment in Class II/1 malocclusion seemed to jeopardize the long-term orthodontic stability, making recurrence possible. PMID:19089223

  13. The Influence of Oral L-Glutamine Supplementation on Muscle Strength Recovery and Soreness Following Unilateral Knee Extension Eccentric Exercise.

    PubMed

    Legault, Zachary; Bagnall, Nicholas; Kimmerly, Derek S

    2015-10-01

    The study aimed to examine the effects that L-glutamine supplementation has on quadriceps muscle strength and soreness ratings following eccentric exercise. It was hypothesized that glutamine ingestion would quicken the recovery rate of peak force production and decrease muscle soreness ratings over a 72-hr recovery period. Sixteen healthy participants (8♀/8♂; 22 ± 4 years) volunteered in a double-blind, randomized, placebo-controlled crossover study. Supplement conditions consisted of isoenergetic placebo (maltodextrin, 0.6 g·kg-1·day-1) and L-glutamine (0.3 g·kg-1·day-1 + 0.3 g·kg-1·day-1 maltodextrin) ingestion once per day over 72 hr. Knee extensor peak torque at 0°, 30°, and 180° per second and muscle soreness were measured before, immediately following, 24, 48, and 72 hr posteccentric exercise. Eccentric exercise consisted of 8 sets (10 repetitions/set) of unilateral knee extension at 125% maximum concentric force with 2-min rest intervals. L-glutamine resulted in greater relative peak torque at 180°/sec both immediately after (71 ± 8% vs. 66 ± 9%), and 72 hr (91 ± 8% vs. 86 ± 7%) postexercise (all, p < .01). In men, L-glutamine produced greater (p < .01) peak torques at 30°/ sec postexercise. Men also produced greater normalized peak torques at 30°/sec (Nm/kg) in the L-glutamine condition than women (all, p < .05). In the entire sample, L-glutamine resulted in lower soreness ratings at 24 (2.8 ± 1.2 vs. 3.4 ± 1.2), 48 (2.6 ± 1.4 vs. 3.9 ± 1.2), and 72 (1.7 ± 1.2 vs. 2.9 ± 1.3) hr postexercise (p < .01). The L-glutamine supplementation resulted in faster recovery of peak torque and diminished muscle soreness following eccentric exercise. The effect of L-glutamine on muscle force recovery may be greater in men than women. PMID:25811544

  14. The Influence of Oral L-Glutamine Supplementation on Muscle Strength Recovery and Soreness Following Unilateral Knee Extension Eccentric Exercise.

    PubMed

    Legault, Zachary; Bagnall, Nicholas; Kimmerly, Derek S

    2015-10-01

    The study aimed to examine the effects that L-glutamine supplementation has on quadriceps muscle strength and soreness ratings following eccentric exercise. It was hypothesized that glutamine ingestion would quicken the recovery rate of peak force production and decrease muscle soreness ratings over a 72-hr recovery period. Sixteen healthy participants (8♀/8♂; 22 ± 4 years) volunteered in a double-blind, randomized, placebo-controlled crossover study. Supplement conditions consisted of isoenergetic placebo (maltodextrin, 0.6 g·kg-1·day-1) and L-glutamine (0.3 g·kg-1·day-1 + 0.3 g·kg-1·day-1 maltodextrin) ingestion once per day over 72 hr. Knee extensor peak torque at 0°, 30°, and 180° per second and muscle soreness were measured before, immediately following, 24, 48, and 72 hr posteccentric exercise. Eccentric exercise consisted of 8 sets (10 repetitions/set) of unilateral knee extension at 125% maximum concentric force with 2-min rest intervals. L-glutamine resulted in greater relative peak torque at 180°/sec both immediately after (71 ± 8% vs. 66 ± 9%), and 72 hr (91 ± 8% vs. 86 ± 7%) postexercise (all, p < .01). In men, L-glutamine produced greater (p < .01) peak torques at 30°/ sec postexercise. Men also produced greater normalized peak torques at 30°/sec (Nm/kg) in the L-glutamine condition than women (all, p < .05). In the entire sample, L-glutamine resulted in lower soreness ratings at 24 (2.8 ± 1.2 vs. 3.4 ± 1.2), 48 (2.6 ± 1.4 vs. 3.9 ± 1.2), and 72 (1.7 ± 1.2 vs. 2.9 ± 1.3) hr postexercise (p < .01). The L-glutamine supplementation resulted in faster recovery of peak torque and diminished muscle soreness following eccentric exercise. The effect of L-glutamine on muscle force recovery may be greater in men than women.

  15. Effects of oral adenosine-5′-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men

    PubMed Central

    2013-01-01

    Background Currently, there is a lack of studies examining the effects of adenosine-5′-triphosphate (ATP) supplementation utilizing a long-term, periodized resistance-training program (RT) in resistance-trained populations. Therefore, we investigated the effects of 12 weeks of 400 mg per day of oral ATP on muscular adaptations in trained individuals. We also sought to determine the effects of ATP on muscle protein breakdown, cortisol, and performance during an overreaching cycle. Methods The study was a 3-phase randomized, double-blind, and placebo- and diet-controlled intervention. Phase 1 was a periodized resistance-training program. Phase 2 consisted of a two week overreaching cycle in which volume and frequency were increased followed by a 2-week taper (Phase 3). Muscle mass, strength, and power were examined at weeks 0, 4, 8, and 12 to assess the chronic effects of ATP; assessment performance variables also occurred at the end of weeks 9 and 10, corresponding to the mid and endpoints of the overreaching cycle. Results There were time (p < 0.001), and group x time effects for increased total body strength (+55.3 ± 6.0 kg ATP vs. + 22.4 ± 7.1 kg placebo, p < 0.001); increased vertical jump power (+ 796 ± 75 ATP vs. 614 ± 52 watts placebo, p < 0.001); and greater ultrasound determined muscle thickness (+4.9 ± 1.0 ATP vs. (2.5 ± 0.6 mm placebo, p < 0.02) with ATP supplementation. During the overreaching cycle, there were group x time effects for strength and power, which decreased to a greater extent in the placebo group. Protein breakdown was also lower in the ATP group. Conclusions Our results suggest oral ATP supplementation may enhance muscular adaptations following 12-weeks of resistance training, and prevent decrements in performance following overreaching. No statistically or clinically significant changes in blood chemistry or hematology were observed. Trial registration ClinicalTrials.gov NCT01508338 PMID

  16. Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines

    PubMed Central

    Mestorino, Nora; Marchetti, María Laura; Lucas, Mariana Florencia; Modamio, Pilar; Zeinsteger, Pedro; Fernández Lastra, Cecilia; Segarra, Ignacio; Mariño, Eduardo Luis

    2016-01-01

    The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 μg/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, Cmax, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0–∞) of both products. In the case of the time to maximum concentration (Tmax), non-parametric tests based on Wilcoxon’s signed rank test were preferred. The comparison of the mean AUC0–∞ values did not reveal any significant differences (311.40 ± 93.05 μg h/mL and 287.71 ± 45.31 μg h/mL, respectively). The results were similar for the Tmax (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean Cmax some significant differences were found (8.73 ± 3.66 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC0–∞ and Tmax values for the reference and test product are within the interval 80–125%, but the 90% confidence intervals for the ratio of Cmax falls outside the proposed interval. It was concluded that Cmax of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation. PMID:27446938

  17. Inverse association of long-acting natriuretic peptide with metabolic syndrome in congestive heart failure patients

    PubMed Central

    2013-01-01

    Aims Long-acting natriuretic peptide (LANP) is one of the peptide hormones in atrial natriuretic peptide (ANP) pro-hormone. Low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients. The aim of this study was to investigate the relationship between fasting serum LANP level and the metabolic syndrome (MetS) among congestive heart failure (CHF) patients. Methods Fasting blood samples were obtained from 186 patients with normal renal function in cardiac clinic outpatients. CHF defined by the American College of Cardiology Foundation and the American Heart Association 2005 Guidelines. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Results Ninety-eight patients (52.7%) had CHF. There was a tendency of increased fasting LANP levels as the NYHA CHF functional classes increased (p = 0.002). Forty-six of the CHF patients (46.9%) had MetS. Fasting LANP level negatively correlated with MetS among CHF patients (p < 0.001). Univariate linear regression analysis showed that BUN (p = 0.026) positively correlated with fasting serum LANP levels, while body weight (p = 0.009), BMI (p = 0.004), homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.024) and HOMA-β (p = 0.001) negatively correlated with fasting serum LANP levels among the CHF patients. Multivariate forward stepwise linear regression analysis of the significant variables showed that the HOMA-β (R2 change = 0.292, p < 0.001) and HOMA-IR (R2 change = 0.081, p = 0.019) were independent predictors of fasting serum LANP levels in CHF patients. Conclusions LANP level is significantly reduced in CHF patients affected by MetS. HOMA-β and HOMA-IR were independent predictors of serum LANP levels in CHF patients. PMID:23566312

  18. Vouchers in Fragile States: Reducing Barriers to Long-Acting Reversible Contraception in Yemen and Pakistan.

    PubMed

    Boddam-Whetham, Luke; Gul, Xaher; Al-Kobati, Eman; Gorter, Anna C

    2016-08-11

    In conflict-affected states, vouchers have reduced barriers to reproductive health services and have enabled health programs to use targeted subsidies to increase uptake of specific health services. Vouchers can also be used to channel funds to public- and private-service providers and improve service quality. The Yamaan Foundation for Health and Social Development in Yemen and the Marie Stopes Society (MSS) in Pakistan-both working with Options Consultancy Services-have developed voucher programs that subsidize voluntary access to long-acting reversible contraceptives (LARCs) and permanent methods (PMs) of family planning in their respective fragile countries. The programs focus on LARCs and PMs because these methods are particularly difficult for poor women to access due to their cost and to provider biases against offering them. Using estimates of expected voluntary uptake of LARCs and PMs for 2014 based on contraceptive prevalence rates, and comparing these with uptake of LARCs and PMs through the voucher programs, we show the substantial increase in service utilization that vouchers can enable by contributing to an expanded method choice. In the governorate of Lahj, Yemen, vouchers for family planning led to an estimated 38% increase in 2014 over the expected use of LARCs and PMs (720 vs. 521 expected). We applied the same approach in 13 districts of Punjab, Khyber Pakhtunkhwa (KPK), and Sindh provinces in Pakistan. Our calculations suggest that vouchers enabled 10 times more women than expected to choose LARCs and PMs in 2014 in those areas of Pakistan (73,639 vs. 6,455 expected). Voucher programs can promote and maintain access to family planning services where existing health systems are hampered. Vouchers are a flexible financing approach that enable expansion of contraceptive choice and the inclusion of the private sector in service delivery to the poor. They can keep financial resources flowing where the public sector is prevented from offering services

  19. Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines.

    PubMed

    Mestorino, Nora; Marchetti, María Laura; Lucas, Mariana Florencia; Modamio, Pilar; Zeinsteger, Pedro; Fernández Lastra, Cecilia; Segarra, Ignacio; Mariño, Eduardo Luis

    2016-01-01

    The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 μg/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, C max, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0-∞) of both products. In the case of the time to maximum concentration (T max), non-parametric tests based on Wilcoxon's signed rank test were preferred. The comparison of the mean AUC0-∞ values did not reveal any significant differences (311.40 ± 93.05 μg h/mL and 287.71 ± 45.31 μg h/mL, respectively). The results were similar for the T max (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean C max some significant differences were found (8.73 ± 3.66 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC0-∞ and T max values for the reference and test product are within the interval 80-125%, but the 90% confidence intervals for the ratio of C max falls outside the proposed interval. It was concluded that C max of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation. PMID:27446938

  20. Vouchers in Fragile States: Reducing Barriers to Long-Acting Reversible Contraception in Yemen and Pakistan

    PubMed Central

    Boddam-Whetham, Luke; Gul, Xaher; Al-Kobati, Eman; Gorter, Anna C

    2016-01-01

    ABSTRACT In conflict-affected states, vouchers have reduced barriers to reproductive health services and have enabled health programs to use targeted subsidies to increase uptake of specific health services. Vouchers can also be used to channel funds to public- and private-service providers and improve service quality. The Yamaan Foundation for Health and Social Development in Yemen and the Marie Stopes Society (MSS) in Pakistan—both working with Options Consultancy Services—have developed voucher programs that subsidize voluntary access to long-acting reversible contraceptives (LARCs) and permanent methods (PMs) of family planning in their respective fragile countries. The programs focus on LARCs and PMs because these methods are particularly difficult for poor women to access due to their cost and to provider biases against offering them. Using estimates of expected voluntary uptake of LARCs and PMs for 2014 based on contraceptive prevalence rates, and comparing these with uptake of LARCs and PMs through the voucher programs, we show the substantial increase in service utilization that vouchers can enable by contributing to an expanded method choice. In the governorate of Lahj, Yemen, vouchers for family planning led to an estimated 38% increase in 2014 over the expected use of LARCs and PMs (720 vs. 521 expected). We applied the same approach in 13 districts of Punjab, Khyber Pakhtunkhwa (KPK), and Sindh provinces in Pakistan. Our calculations suggest that vouchers enabled 10 times more women than expected to choose LARCs and PMs in 2014 in those areas of Pakistan (73,639 vs. 6,455 expected). Voucher programs can promote and maintain access to family planning services where existing health systems are hampered. Vouchers are a flexible financing approach that enable expansion of contraceptive choice and the inclusion of the private sector in service delivery to the poor. They can keep financial resources flowing where the public sector is prevented from

  1. A novel, long-acting glucagon-like peptide receptor-agonist: dulaglutide

    PubMed Central

    Gurung, Tara; Shyangdan, Deepson S; O’Hare, Joseph Paul; Waugh, Norman

    2015-01-01

    Background Dulaglutide is a new, long-acting glucagon-like peptide analogue in the treatment of type 2 diabetes. It is available in two doses, 0.75 and 1.5 mg, given by injection once weekly. This systematic review reports the effectiveness and safety of dulaglutide in type 2 diabetes in dual and triple therapy. Methods MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, and conference abstracts were searched from 2005 to August 2014, and updated in January 2015. Company websites and references of included studies were checked for potentially relevant studies. European Medicines Agency and US Food and Drug Administration websites were searched. Results Four trials were included. All were manufacturer-funded randomized controlled trials from the Assessment of Weekly Administration of Dulaglutide in Diabetes (AWARD) program. AWARD-1 compared dulaglutide 1.5 mg against exenatide 10 µg twice daily and placebo, AWARD-2 compared dulaglutide 0.75 and 1.5 mg against insulin glargine, AWARD-5 compared dulaglutide 0.75 and 1.5 mg against sitagliptin 100 mg and placebo, and AWARD-6 compared dulaglutide 1.5 mg against liraglutide 1.8 mg. The duration of follow-up in the trials ranged from 26 to 104 weeks. The primary outcome of all the included trials was change in HbA1c. At 26 weeks, greater HbA1c reductions were seen with dulaglutide than with twice daily exenatide (dulaglutide 1.5/0.75 mg: −1.5%/−1.3%; exe: 0.99%) and sitagliptin (1.5/0.75 mg −1.22%/−1.01%; sitagliptin: −0.6%). HbA1c change was greater with dulaglutide 1.5 mg (−1.08%) than with glargine (−0.63%), but not with dulaglutide 0.75 mg (−0.76%). Dulaglutide 1.5 mg was found to be noninferior to liraglutide 1.8 mg. More patients treated with dulaglutide achieved HbA1c targets of <7% and ≤6.5%. Reduction in weight was greater with dulaglutide than with sitagliptin and exenatide. Hypoglycemia was infrequent. The main adverse events were nausea, diarrhea, and vomiting. Conclusion

  2. A radio-ligand receptor assay for the long-acting thyroid stimulator. Inhibition by the long-acting thyroid stimulator of the binding of radioiodinated thyroid-stimulating hormone to human thyroid membranes.

    PubMed Central

    Mehdi, S Q; Nussey, S S

    1975-01-01

    Highly purified bovine TSH (thyroid-stimulating hormone) was labelled with 125I by using very low concentrations of chloramine-T. Human thyroid membranes prepared by discontinuous sucrose-density-gradient centrifugation were homogeneous on examination by electron microscopy. Incubation of radioiodinated TSH with the membranes showed that radioactivity could be bound to the membranes. Under the experimental conditions described here, binding was dependent on time and temperature and was a saturable phenomenon. Preincubation of the membranes with unlabelled hormone inhibited the subsequent binding of 125I-labelled TSH. Similarly, inhibition by the long-acting thyroid stimulator also showed a saturation behaviour. A rapid and sensitive method for the detection of the long-acting thyroid stimulator is described. Images PLATE 1 PLATE 2 PMID:1191248

  3. Chronic oral administration of Ang-(1-7) improves skeletal muscle, autonomic and locomotor phenotypes in muscular dystrophy.

    PubMed

    Sabharwal, Rasna; Cicha, Michael Z; Sinisterra, Ruben D M; De Sousa, Frederico B; Santos, Robson A; Chapleau, Mark W

    2014-07-01

    Muscular dystrophies are a group of heterogeneous genetic disorders that cause progressive muscle weakness and wasting, dilated cardiomyopathy and early mortality. There are different types of muscular dystrophies with varying aetiologies but they all have a common hallmark of myofibre degeneration, atrophy and decreased mobility. Mutation in Sgcd (sarcoglycan-δ), a subunit of dystrophin glycoprotein complex, causes LGMD2F (limb girdle muscular dystrophy 2F). Previously, we have reported that Sgcd-deficient (Sgcd-/-) mice exhibit AngII (angiotensin II)-induced autonomic and skeletal muscle dysfunction at a young age, which contributes to onset of dilated cardiomyopathy and mortality at older ages. Two counter-regulatory RAS (renin-angiotensin system) pathways have been identified: deleterious actions of AngII acting on the AT1R (AngII type 1 receptor) compared with the protective actions of Ang-(1-7) [angiotensin-(1-7)] acting on the receptor Mas. We propose that the balance between the AngII/AT1R and Ang-(1-7)/Mas axes is disturbed in Sgcd-/- mice. Control C57BL/6J and Sgcd-/- mice were treated with Ang-(1-7) included in hydroxypropyl β-cyclodextrin (in drinking water) for 8-9 weeks beginning at 3 weeks of age. Ang-(1-7) treatment restored the AngII/AT1R compared with Ang-(1-7)/Mas balance, decreased oxidative stress and fibrosis in skeletal muscle, increased locomotor activity, and prevented autonomic dysfunction without lowering blood pressure in Sgcd-/- mice. Our results suggest that correcting the early autonomic dysregulation by administering Ang-(1-7) or enhancing its endogenous production may provide a novel therapeutic approach in muscular dystrophy.

  4. [Functional state of mastication muscles and of separate factors of oral local immunity during non removable dentures use].

    PubMed

    Kochubeĭnik, A V

    2010-01-01

    There were examined 100 people of the age from 18 to 31 years with intact dentitions and physiological byte (control group) and 65 patients of the age from 19 to 60 years with hard dental tissue defects, one- and two-sided included defects of dentitions requiring in installation of non removable dentures. Significantly different indicators in healthy persons and in persons with periodontal diseases and mastication muscles para-functions and also in patients before and after prosthetic treatment by non removable dentures were found.

  5. Use of Oral Mucoperiosteal and Pterygo-Masseteric Muscle Flaps as Interposition Material in Surgery of Temporomandibular Joint Ankylosis: A Comparative Study

    PubMed Central

    Anyanechi, CE; Osunde, OD; Bassey, GO

    2015-01-01

    Background: The most common complication of surgery for the release of temporomandibular joint (TMJ) ankylosis is relapse of the ankylosis. To prevent re-ankylosis, a variety of interpositional materials have been used. Aim: The aim was to compare the surgical outcome of oral mucoperiosteal flap, not hitherto used as interpositional material, with pterygo-masseteric muscles flap after surgical release of TMJ ankylosis. Subjects and Methods: This was a prospective randomized study of all consecutive patients treated for the release of complete TMJ bony ankylosis, from January 2003 to December 2012, at the Oral and Maxillofacial unit of our institution. The patients were randomized into two groups: The pterygo-masseteric group comprises 22 patients while the oral mucoperiosteal group had 23 patients. Information on demographics, clinical characteristics, and postoperative complications over a 5 year follow-up period were obtained, and analyzed using the statistical package for social sciences (Statistical Package for the Social Sciences version 13, Chicago, IL, USA). A P < 0.05 was considered significant. Results: The age of the patients ranged from 15 to 28 mean 20.3 (3.35) years while the duration of ankylosis ranged from 2 to 16 mean 5.1 (3.4) years. The baseline demographic (gender; P = 0.92; side; P = 0.58) and clinical characteristics in terms of etiology (P = 0.60) and age (P = 0.52) were comparable in both treatment groups. All the patients presented with complete bony TMJ ankylosis with a preoperative inter-incisal distance of <0.5 cm. The intraoperative mouth opening achieved ranged from 4 cm to 5 cm, mean 4.6 (0.27) cm and this was not different for either group (P = 0.51). The patients were followed up postoperatively for a period ranging from 3 to 5 years, mean 3.4 (0.62) years. The mouth opening decreased, over the period of postoperative review, from the initial range of 4–5 cm to 2.9–3.6 cm, and this was not different in both groups (P = 0

  6. Multispecies resistance of cattle gastrointestinal nematodes to long-acting avermectin formulations in Mato Grosso do Sul.

    PubMed

    Borges, Fernando de Almeida; Borges, Dyego Gonçalves Lino; Heckler, Rafael Pereira; Neves, Juliana Paniago Lordello; Lopes, Fernando Gonçalves; Onizuka, Marcel Kenzo Vilalba

    2015-09-15

    The use of long-acting avermectins (AVMs) in cattle to treat infections with gastrointestinal nematodes was common in Brazil until its prohibition by state authorities. The prohibition; however, was rescinded in 2015, but a scientific discussion of the pros and cons of the use of these formulations is necessary. We evaluated the levels of resistance to 1.0 and 3.5% doramectin and to 3.15% ivermectin in cattle. The worms in animals treated with 3.5% doramectin were characterized by the suppression of oviposition and by a higher proportion of adult females carrying no eggs. Haemonchus placei, Cooperia punctata, C. pectinata, C. spatulata, and Oesophagostomum radiatum were resistant to the above compositions. The administration of long-acting AVM formulations did not result in a higher efficacy against these helminth populations.

  7. The Potential Role of Long-acting Injectable Antipsychotics in People with Schizophrenia and Comorbid Substance Use

    PubMed Central

    Koola, Maju Mathew; Wehring, Heidi J.; Kelly, Deanna L.

    2012-01-01

    Objective Treatment of schizophrenia in patients with comorbid substance use (alcohol/illicit drug use, abuse or dependence) presents challenges for public health systems. Substance use in people with schizophrenia is up to four times greater than the general population and is associated with medication nonadherence and poor outcomes. Therefore, continuous antipsychotic treatment in this population may pose more of a challenge than for those with schizophrenia alone. Many clinical trials and treatment recommendations in schizophrenia do not take into consideration substance use as people with comorbid substance use have typically been excluded from most antipsychotic trials. Nonetheless, antipsychotic treatment appears to be as efficacious in this population, although treatment discontinuation remains high. The objective of this review was to highlight the importance and utility of considering long-acting injectable antipsychotics for patients with schizophrenia and comorbid substance use. Methods We did a literature search using PubMed with key words schizophrenia and substance use/abuse/dependence, nonadherence, antipsychotics, long acting injectables, relapse, and psychosocial interventions. We limited our search to human studies published in English and 4,971 articles were identified. We focused on clinical trials, case reports, case series, reviews and meta-analyses resulting in 125 articles from 1975-2011. Results Our review suggests the potential role of long-acting injectables for people with comorbid substance use and schizophrenia in leading to improvements in psychopathology, relapse prevention, fewer rehospitalizations, and better outcomes. Conclusions While more research is needed, long-acting antipsychotics should be considered an important option in the management of people with schizophrenia and comorbid substance use. PMID:22754405

  8. Knowledge and perception on long acting and permanent contraceptive methods in adigrat town, tigray, northern ethiopia: a qualitative study.

    PubMed

    Gebremariam, Alem; Addissie, Adamu

    2014-01-01

    Background. Long acting and permanent contraceptive methods have the potential to reduce unintended pregnancies but the contraceptive choice and utilization in Ethiopia are highly dominated by short term contraceptives. Objective. To assess the knowledge and perception on long acting and permanent contraceptives of married women and men in Northern Ethiopia. Method. A qualitative method was conducted in Adigrat on January, 2012. Four focus group discussions with married women and men and six in-depth interviews with family planning providers were conducted. Content analysis was used to synthesize the data. Result. Participants' knowledge on long acting and permanent contraceptives is limited to recognizing the name of the methods. Most of the participants are not able to identify permanent methods as a method of contraception. They lack basic information on how these methods work and how they can use it. Women had fears and rumors about each of these methods. They prefer methods which do not require any procedure. Family planning providers stated as they have weakness on counseling of all contraceptive choices. Conclusion. There are personal barriers and knowledge gaps on these contraceptive methods. Improving the counseling service program can help women to increase knowledge and avoid misconceptions of each contraceptive choice.

  9. Knowledge and Perception on Long Acting and Permanent Contraceptive Methods in Adigrat Town, Tigray, Northern Ethiopia: A Qualitative Study

    PubMed Central

    Addissie, Adamu

    2014-01-01

    Background. Long acting and permanent contraceptive methods have the potential to reduce unintended pregnancies but the contraceptive choice and utilization in Ethiopia are highly dominated by short term contraceptives. Objective. To assess the knowledge and perception on long acting and permanent contraceptives of married women and men in Northern Ethiopia. Method. A qualitative method was conducted in Adigrat on January, 2012. Four focus group discussions with married women and men and six in-depth interviews with family planning providers were conducted. Content analysis was used to synthesize the data. Result. Participants' knowledge on long acting and permanent contraceptives is limited to recognizing the name of the methods. Most of the participants are not able to identify permanent methods as a method of contraception. They lack basic information on how these methods work and how they can use it. Women had fears and rumors about each of these methods. They prefer methods which do not require any procedure. Family planning providers stated as they have weakness on counseling of all contraceptive choices. Conclusion. There are personal barriers and knowledge gaps on these contraceptive methods. Improving the counseling service program can help women to increase knowledge and avoid misconceptions of each contraceptive choice. PMID:25140252

  10. Targets, attitudes, and goals of psychiatrists treating patients with schizophrenia: key outcome drivers, role of quality of life, and place of long-acting antipsychotics

    PubMed Central

    de Bartolomeis, Andrea; Fagiolini, Andrea; Vaggi, Marco; Vampini, Claudio

    2016-01-01

    Purpose This survey of Italian psychiatrists was conducted to better define drivers of schizophrenia treatment choice in real-life practice, particularly for use of long-acting injectable (LAI) antipsychotics. Methods Between October 15 and December 15, 2014, 1,000 surveys were sent to psychiatrists who treat schizophrenic patients; 709 completed questionnaires were analyzed (71% response rate). Results The two most important factors determining therapy success were efficacy (75% of responses) and tolerability (45%) followed by global functioning (24%) and quality of life (17%). LAI antipsychotics were most often used to facilitate regular treatment monitoring (49%), and 41% of psychiatrists thought that patients with low adherence who had failed oral therapy were well-suited for LAI antipsychotics. Only 4% of respondents saw LAI antipsychotics as appropriate for patients without other therapeutic options. Conclusion Although efficacy and tolerability were the most common factors used to evaluate treatment success in schizophrenia, psychiatrists also consider QoL and global functioning to be important. PMID:26811682

  11. Long-term treatment of acromegaly with a long-acting analogue of somatostatin, octreotide.

    PubMed

    Page, M D; Millward, M E; Taylor, A; Preece, M; Hourihan, M; Hall, R; Scanlon, M F

    1990-02-01

    We have treated 16 acromegalic patients for up to 44 months with octreotide in varying doses. Growth hormone levels were suppressed in 14 patients with associated clinical improvement. IGF-1 levels were measured in 12 and fell into the normal range in 10. Prolactin was suppressed in six hyperprolactinaemic patients but was unaltered in normoprolactinaemic acromegalic patients. Post-prandial hyperglycaemia with impaired insulin secretion was noted in all patients, and one patient required oral hypoglycaemic agents. Octreotide did not affect thyroid function. CT scans from before and after six months of treatment demonstrated minimal tumour shrinkage in only two patients. Octreotide was well tolerated with no serious haematological or biochemical disturbance and no evidence of malabsorption. Two patients developed gallstones. Octreotide is effective in acromegaly. The development of gallstones is the only serious adverse event we have encountered.

  12. [Pharmacological studies of long-acting phenothiazines with particular reference to fluphenazine decanoate (author's transl)].

    PubMed

    Chen, P C

    1978-10-01

    A long-term study was performed on the effects of fluphenazine decanoate and the results were compared with those of fluphenazine-2HCl and fluphenazine enanthate. These agents given orally were equipotent in inhibiting the motility of mice. With subcutaneous administration, decanoate and enanthate showed a clearly prolonged action, whereas fluphenazine-2HCl was effective for only 3 days. Decanoate and enanthate did not produce marked hypothermia in rats. Like enanthate, decanoate inhibited, for a long duration, apomorphine-induced stereotyped behavior and methamphetamine group toxicity in mice, as well as induced catalepsy in rats. It was found that fluphenazine-2HCl markedly inhibited certain agonists-induced contraction of isolated preparations while enanthate and decanoate inhibited these contractions almost equally. In rats, enanthate induced a persistent hypotension and marked changes in ECG while decanoate showed a transient hypotension and slight changes in ECG. In the study of rat brain catecholamine turnover, these three drugs significantly increased dopamine turnover, and decanoate and enanthate were found to have prolonged effects. No significant change in noradrenaline turnover was observed. These results indicate that fluphenazine decanoate has the same spectrum of activity as enanthate except for its slower onset, weaker potency and longer duration of action. A prolonged tranquilizing effect was most evident.

  13. Engineering a long-acting, potent GLP-1 analog for microstructure-based transdermal delivery

    PubMed Central

    Yang, Peng-Yu; Zou, Huafei; Chao, Elizabeth; Sherwood, Lance; Nunez, Vanessa; Keeney, Michael; Ghartey-Tagoe, Esi; Ding, Zhongli; Quirino, Herlinda; Luo, Xiaozhou; Welzel, Gus; Chen, Guohua; Singh, Parminder; Woods, Ashley K.; Schultz, Peter G.; Shen, Weijun

    2016-01-01

    Antidiabetic treatments aiming to reduce body weight are currently gaining increased interest. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist administered twice daily via s.c. injection, improves glycemic control, often with associated weight reduction. To further improve the therapeutic efficacy of exendin-4, we have developed a novel peptide engineering strategy that incorporates a serum protein binding motif onto a covalent side-chain staple and applied to the peptide to enhance its helicity and, as a consequence, its potency and serum half-life. We demonstrated that one of the resulting peptides, E6, has significantly improved half-life and glucose tolerance in an oral glucose tolerance test in rodents. Chronic treatment of E6 significantly decreased body weight and fasting blood glucose, improved lipid metabolism, and also reduced hepatic steatosis in diet-induced obese mice. Moreover, the high potency of E6 allowed us to administer this peptide using a dissolvable microstructure-based transdermal delivery system. Pharmacokinetic and pharmacodynamic studies in guinea pigs showed that a single 5-min application of a microstructure system containing E6 significantly improved glucose tolerance for 96 h. This delivery strategy may offer an effective and patient-friendly alternative to currently marketed GLP-1 injectables and can likely be extended to other peptide hormones. PMID:27035989

  14. Prevalence and factors affecting use of long acting and permanent contraceptive methods in Jinka town, Southern Ethiopia: a cross sectional study

    PubMed Central

    Mekonnen, Getachew; Enquselassie, Fikre; Tesfaye, Gezahegn; Semahegn, Agumasie

    2014-01-01

    Introduction In Ethiopia, knowledge of contraceptive methods is high though there is low contraceptive prevalence rate. This study was aimed to assess prevalence and associated factors of long acting and permanent contraceptive methods in Jinka town, southern Ethiopia. Methods Community based cross sectional survey was conducted to assess the prevalence and factors affecting long acting and permanent methods of contraceptives utilization from March to April 2008. Eight hundred child bearing age women were participated in the quantitative study and 32 purposively selected focus group discussants were participated in the qualitative study. Face to face interview was used for data collection. Data were analyzed by SPSS version 13.0 statistical software. Descriptive statistics and logistic regression were computed to analyze the data. Results The prevalence of long acting and permanent contraceptive method was 7.3%. Three fourth (76.1%) of the women have ever heard about implants and implant 28 (50%) were the most widely used method. Almost two third of women had intention to use long acting and permanent methods. Knowledge of contraceptive and age of women have significant association with the use of long acting and permanent contraceptive methods. Conclusion The overall prevalence of long acting and permanent contraceptive method was low. Knowledge of contraceptive and age of women have significant association with use of long acting and permanent contraceptive. Extensive health information should be provided. PMID:25404960

  15. Effects of long-acting beta 2-adrenoceptor agonists on mast cells of rat, guinea pig, and human.

    PubMed

    Lau, H Y; Wong, P L; Lai, C K; Ho, J K

    1994-10-01

    The effects of two recently developed long-acting beta 2-adrenoceptor agonists, formoterol and salmeterol, on mast cells from different sources were compared with those of the prototype short-acting analogue, salbutamol. With the exception of high concentrations of salmeterol (> 10(-5) M), none of the tested beta 2-adrenoceptor agonists inhibited the anti-IgE-induced histamine release from rat peritoneal mast cells. In contrast, all three compounds dose dependently inhibited the immunologically induced histamine release from isolated lung mast cells of guinea pig and human at concentrations < or = 10(-5) M.

  16. Medical treatment of uterine myoma with long-acting gonadotropin-releasing hormone agonist prior to myomectomy.

    PubMed

    Liu, C H; Lin, Y S; Lin, C C; Tzeng, C C; Chou, C Y

    1993-06-01

    A less bulky uterine myoma is technically easier to deal with during surgery. Recently gonadotropin-releasing hormone agonists (GnRH-a) have been used for the purpose of medical hypophysectomy, thereby reducing the size of uterine myomas. Ten premenopausal women with infertility and intramural-submucous myoma manifesting with menorrhagia and obstruction of the tubal ostia were recruited for this study. A long-acting depot GnRH-a, Decapeptyl, was given intramuscularly every four weeks for three months as an adjunct prior to myomectomy. Luteinizing hormone, follicular stimulating hormone and estradiol declined to the menopausal range following treatment. The size of the myoma decreased to a mean of 32.3 +/- 13.3% of the original volume. Myomectomy was performed in eight patients at the end of the study. Remarkably little blood loss was observed during the surgery. All of the patients had their uteri preserved, and six out of eight patients achieved pregnancy within 12 months after surgery. Our results indicate that monthly administration of long-acting GnRH-a significantly reduces the myoma volume and makes myomectomy technically easier to perform with the possibility of reduced complication rates and better preservation of future fertility.

  17. Pharmacokinetics of a long-acting oxytetracycline preparation in ring-necked pheasants, great horned owls, and Amazon parrots.

    PubMed

    Teare, J A; Schwark, W S; Shin, S J; Graham, D L

    1985-12-01

    After a single IV or IM dose of a long-acting oxytetracycline (OTC) preparation, serum concentrations were determined at various times in the ring-necked pheasant, great horned owl, and Amazon parrot. Pharmacokinetic parameters, including serum half-life (t1/2) and apparent volume of distribution (Vd) were calculated from the OTC concentration-time curves for each species and route of administration. Significant differences (P less than 0.05) were found in the t1/2 and Vd parameters between species and routes of administration. Dosage regimens to maintain minimum OTC concentration of 5 micrograms/ml of serum were calculated from the t 1/2 and Vd values obtained, using steady-state pharmacokinetics. In the pheasant, the calculated mean IV dose was 23 mg/kg of body weight every 6 hours, whereas the mean IM dose was 43 mg/kg every 24 hours. The mean IM dose was 16 mg/kg every 24 hours for the owl and 58 mg/kg every 24 hours for the parrot. The small volumes required for treatment, the long-dosing interval obtainable, and the broad spectrum of antimicrobial activity of the long-acting OTC preparation studied offered major advantages over other antibiotics commonly used in treating avian species. PMID:4083606

  18. Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats.

    PubMed

    Cefalu, William T; Wang, Zhong Q; Zhang, Xian H; Baldor, Linda C; Russell, James C

    2002-06-01

    Human studies suggest that chromium picolinate (CrPic) decreases insulin levels and improves glucose disposal in obese and type 2 diabetic populations. To evaluate whether CrPic may aid in treatment of the insulin resistance syndrome, we assessed its effects in JCR:LA-corpulent rats, a model of this syndrome. Male lean and obese hyperinsulinemic rats were randomly assigned to receive oral CrPic [80 microg/(kg. d); n = 5 or 6, respectively) in water or to control conditions (water, n = 5). After 3 mo, a 120-min intraperitoneal glucose tolerance test (IPGTT) and a 30-min insulin tolerance test were performed. Obese rats administered CrPic had significantly lower fasting insulin levels (1848 +/- 102 vs. 2688 +/- 234 pmol/L; P < 0.001; mean +/- SEM) and significantly improved glucose disappearance (P < 0.001) compared with obese controls. Glucose and insulin areas under the curve for IPGTT were significantly less for obese CrPic-treated rats than in obese controls (P < 0.001). Obese CrPic-treated rats had lower plasma total cholesterol (3.57 +/- 0.28 vs. 4.11 +/- 0.47 mmol/L, P < 0.05) and higher HDL cholesterol levels (1.92 +/- 0.09 vs. 1.37 +/- 0.36 mmol/L, P < 0.01) than obese controls. CrPic did not alter plasma glucose or cholesterol levels in lean rats. Total skeletal muscle glucose transporter (Glut)-4 did not differ among groups; however, CrPic significantly enhanced membrane-associated Glut-4 in obese rats after insulin stimulation. Thus, CrPic supplementation enhances insulin sensitivity and glucose disappearance, and improves lipids in male obese hyperinsulinemic JCR:LA-corpulent rats.

  19. Expression and Characterization of a Potent Long-Acting GLP-1 Receptor Agonist, GLP-1-IgG2σ-Fc

    PubMed Central

    Yang, Yi; Chen, Fang; Wan, Deyou; Liu, Yunhui; Yang, Li; Feng, Hongru; Cui, Xinling; Gao, Xin; Song, Haifeng

    2016-01-01

    Human GLP-1 (glucagon-like peptide-1) can produce a remarkable improvement in glycemic control in patients with type 2 diabetes. However, its clinical benefits are limited by its short half-life, which is less than 2 min because of its small size and rapid enzymatic inactivation by dipeptidyl peptidase IV. We engineered GLP-1-IgG2σ-Fc, a 68-kDa fusion protein linking a variant human GLP-1 (A8G/G26E/R36G) to a human IgG2σ constant heavy-chain. A stably transfected Chinese hamster ovary cell line was obtained using electroporation. Western blotting showed that the expressed protein was immunoreactive to both GLP-1 and IgG antibodies. GLP-1-IgG2σ-Fc stimulated insulin secretion from INS-1 cells in a dose- and glucose-dependent manner and increased insulin mRNA expression. The half-life of GLP-1-IgG2σ-Fc in cynomolgus monkeys was approximately 57.1 ± 4.5 h. In the KKAy mouse model of diabetes, one intraperitoneal injection of GLP-1-IgG2σ-Fc (1 mg/kg) reduced blood glucose levels for 5 days. A 4-week repeat-administration study identified sustained effects on blood glucose levels. Oral glucose tolerance tests conducted at the beginning and end of this 4-week period showed that GLP-1-IgG2σ-Fc produced a stable glucose lowering effect. In addition, KKAy mice treated with GLP-1-IgG2σ-Fc showed statistically significant weight loss from day 23. In conclusion, these properties of GLP-1-IgG2σ-Fc demonstrated that it represented a potential long-acting GLP-1 receptor agonist for the treatment of type 2 diabetes. PMID:27232339

  20. Diphtheria Toxin- and GFP-Based Mouse Models of Acquired Hypoparathyroidism and Treatment With a Long-Acting Parathyroid Hormone Analog.

    PubMed

    Bi, Ruiye; Fan, Yi; Lauter, Kelly; Hu, Jing; Watanabe, Tomoyuki; Cradock, Jim; Yuan, Quan; Gardella, Thomas; Mannstadt, Michael

    2016-05-01

    Hypoparathyroidism (HP) arises most commonly from parathyroid (PT) gland damage associated with neck surgery, and is typically treated with oral calcium and active vitamin D. Such treatment effectively increases levels of serum calcium (sCa), but also brings risk of hypercalciuria and renal damage. There is thus considerable interest in using PTH or PTH analogs to treat HP. To facilitate study of this disease and the assessment of new treatment options, we developed two mouse models of acquired HP, and used them to assess efficacy of PTH(1-34) as well as a long-acting PTH analog (LA-PTH) in regulating blood calcium levels. In one model, we used PTHcre-iDTR mice in which the diphtheria toxin (DT) receptor (DTR) is selectively expressed in PT glands, such that systemic DT administration selectively ablates parathyroid cells. For the second model, we generated GFP-PT mice in which green fluorescent protein (GFP) is selectively expressed in PT cells, such that parathyroidectomy (PTX) is facilitated by green fluorescence of the PT glands. In the PTHcre-iDTR mice, DT injection (2 × 5 μg/kg, i.p.) resulted in moderate yet consistent reductions in serum PTH and sCa levels. The more severe hypoparathyroid phenotype was observed in GFP-PT mice following GFP-guided PTX surgery. In each model, a single subcutaneous injection of LA-PTH increased sCa levels more effectively and for a longer duration (>24 hours) than did a 10-fold higher dose of PTH(1-34), without causing excessive urinary calcium excretion. These new mouse models thus faithfully replicate two degrees of acquired HP, moderate and severe, and may be useful for assessing potential new modes of therapy. © 2015 American Society for Bone and Mineral Research. PMID:26678919

  1. Oral administration of amino acidic supplements improves protein and energy profiles in skeletal muscle of aged rats: elongation of functional performance and acceleration of mitochondrial recovery in adenosine triphosphate after exhaustive exertion.

    PubMed

    Chen Scarabelli, Carol; McCauley, Roy B; Yuan, Zhaokan; Di Rezze, Justin; Patel, David; Putt, Jeff; Raddino, Riccardo; Allebban, Zuhair; Abboud, John; Scarabelli, Gabriele M; Chilukuri, Karuna; Gardin, Julius; Saravolatz, Louis; Faggian, Giuseppe; Mazzucco, Alessandro; Scarabelli, Tiziano M

    2008-06-01

    Sarcopenia is an inevitable age-related degenerative process chiefly characterized by decreased synthesis of muscle proteins and impaired mitochondrial function, leading to progressive loss of muscle mass. Here, we sought to probe whether long-term administration of oral amino acids (AAs) can increase protein and adenosine triphosphate (ATP) content in the gastrocnemius muscle of aged rats, enhancing functional performance. To this end, 6- and 24-month-old male Fisher 344 rats were divided into 3 groups: group A (6-month-old rats) and group B (24-month-old rats) were used as adult and senescent control group, respectively, while group C (24-month-old rats) was used as senescent treated group and underwent 1-month oral treatment with a mixture of mainly essential AAs. Untreated senescent animals exhibited a 30% reduction in total and fractional protein content, as well as a 50% reduction in ATP content and production, compared with adult control rats (p <0.001). Long-term supplementation with mixed AAs significantly improved protein and high-energy phosphate content, as well as the rate of mitochondrial ATP production, conforming their values to those of adult control animals (p <0.001). The improved availability of protein and high-energy substrates in the gastrocnemius muscle of treated aged rats paralleled a significant enhancement in functional performance assessed by swim test, with dramatic elongation of maximal exertion times compared with untreated senescent rats (p <0.001). In line with these findings, we observed that, after 6 hours of rest following exhaustive swimming, the recovery in mitochondrial ATP content was approximately 70% in adult control rats, approximately 60% in senescent control rats, and normalized in treated rats as compared with animals of the same age unexposed to maximal exertion (p <0.001). In conclusion, nutritional supplementation with oral AAs improved protein and energy profiles in the gastrocnemius of treated rats, enhancing

  2. Improving Access to Long-Acting Contraceptive Methods and Reducing Unplanned Pregnancy Among Women with Substance Use Disorders.

    PubMed

    Black, Kirsten I; Day, Carolyn A

    2016-01-01

    Much has been written about the consequences of substance use in pregnancy, but there has been far less focus on the prevention of unintended pregnancies in women with substance use disorders (SUDs). We examine the literature on pregnancy incidence for women with SUDs, the clinical and economic benefits of increasing access to long-acting reversible contraceptive (LARC) methods in this population, and the current hurdles to increased access and uptake. High rates of unintended pregnancies and poor physical and psychosocial outcomes among women with SUDs underscore the need for increased access to, and uptake of, LARC methods among these women. A small number of studies that focused on improving access to contraception, especially LARC, via integrated contraception services predominantly provided in drug treatment programs were identified. However, a number of barriers remain, highlighting that much more research is needed in this area. PMID:27199563

  3. Quantitative determination of amorphous nicardipine hydrochloride in long acting formula (NIC-LA) using light anhydrous silicic acid.

    PubMed

    Kohinata, Takeru; Fujii, Mitsuo; Nakamura, Souichiro; Hamada, Noritaka; Yonemochi, Etsuo; Terada, Katsuhide

    2004-12-01

    We investigated a method to quantitatively determine amorphous nicardipine hydrochloride (NIC) in the NIC-long acting formula (LA) model formulas prepared using NIC, light anhydrous silicic acid (LASA) and carboxymethylethylcellulose (CMEC). Consequently, since the quantity of total NIC in the formula can be determined by means of HPLC and crystal NIC can be determined by the differential scanning calorimetry (DSC) method because the heat of fusion (85.08 J/g) of NIC is constant and unaffected by excipients, we developed the HPLC-DSC method by which the quantity of amorphous NIC is calculated as the difference between the quantity of total NIC determined by HPLC and the quantity of crystal NIC determined by DSC. This practical HPLC-DSC method was confirmed to have good accuracy and reproducibility.

  4. PHARMACOKINETIC EVALUATION OF A LONG-ACTING FENTANYL SOLUTION AFTER TRANSDERMAL ADMINISTRATION IN HELMETED GUINEAFOWL (NUMIDA MELEAGRIS).

    PubMed

    Waugh, Lynnette; Knych, Heather; Cole, Gretchen; D'Agostino, Jennifer

    2016-06-01

    The objective of this study was to investigate the pharmacokinetics of a long-acting fentanyl solution in helmeted guineafowl ( Numida meleagris ) after transdermal administration. Twenty-one guineafowl received a single administration of 5 mg/kg of fentanyl transdermal solution. No adverse effects on behavior were appreciated. Plasma fentanyl concentrations were determined by liquid chromatography-mass spectrometry analysis of protein-precipitated samples. Mean maximum plasma concentration was 228.8 ng/ml at 4 hr. The mean plasma terminal half-life was 33.2 hr. At 168 hr the mean plasma concentration was 1.3 ng/ml. A single topical dose of 5 mg/kg appears to be safe for use in this species and maintained plasma concentrations above those reported to be analgesic in dogs for at least 7 days.

  5. [Efficiency of a pharmaceutical care program for long-acting parenteral antipsychotics in the health area of Santiago de Compostela].

    PubMed

    Vázquez-Mourelle, Raquel; Parrondo, Carmen Durán; López-Pardo Pardo, Estrella; Carracedo-Martínez, Eduardo

    2016-01-01

    In the healthcare area of Santiago de Compostela (Spain), the therapeutic subgroup "other antipsychotics" represented the fifth largest outpatient expenditure in 2013. More than half of this expenditure corresponded to long-acting parenteral forms of paliperidone and risperidone. Over a 12-month period, the implementation of a pharmaceutical care program based on process management and coordination of actions between health professionals in both levels of care represented savings of € 636,391.01 for the organization and a direct saving of € 16,767.36 and 9,008 trips to the pharmacy for patients. This study shows the efficiency of the program, which was facilitated by its situation in an area of integrated management and the use the unified medical records and electronic prescription, elements that will enable the future implementation of similar programmes. The new registries and healthcare interventions will allow reliable evaluation of their effectiveness in terms of treatment adherence, relapses and hospitalisations.

  6. Improving Access to Long-Acting Contraceptive Methods and Reducing Unplanned Pregnancy Among Women with Substance Use Disorders

    PubMed Central

    Black, Kirsten I.; Day, Carolyn A.

    2016-01-01

    Much has been written about the consequences of substance use in pregnancy, but there has been far less focus on the prevention of unintended pregnancies in women with substance use disorders (SUDs). We examine the literature on pregnancy incidence for women with SUDs, the clinical and economic benefits of increasing access to long-acting reversible contraceptive (LARC) methods in this population, and the current hurdles to increased access and uptake. High rates of unintended pregnancies and poor physical and psychosocial outcomes among women with SUDs underscore the need for increased access to, and uptake of, LARC methods among these women. A small number of studies that focused on improving access to contraception, especially LARC, via integrated contraception services predominantly provided in drug treatment programs were identified. However, a number of barriers remain, highlighting that much more research is needed in this area. PMID:27199563

  7. Provider Bias in Long-Acting Reversible Contraception (LARC) Promotion and Removal: Perceptions of Young Adult Women

    PubMed Central

    Kramer, Renee D.; Ryder, Kristin M.

    2016-01-01

    Long-acting reversible contraception (LARC) is effective and acceptable. However, concern exists about potential provider bias in LARC promotion. No study has documented contraceptive users’ attitudes toward or experiences with provider influence and bias regarding LARC. We collected qualitative data in 2014 to address this gap. Participants were 50 young adult women with any history of contraceptive use (including LARC) in Dane County, Wisconsin. Women often described providers as a trusted source of contraceptive information. However, several women reported that their preferences regarding contraceptive selection or removal were not honored. Furthermore, many participants believed that providers recommend LARC disproportionately to socially marginalized women. We encourage contraceptive counseling and removal protocols that directly address historical reproductive injustices and that honor patients’ wishes. PMID:27631741

  8. PHARMACOKINETIC EVALUATION OF A LONG-ACTING FENTANYL SOLUTION AFTER TRANSDERMAL ADMINISTRATION IN HELMETED GUINEAFOWL (NUMIDA MELEAGRIS).

    PubMed

    Waugh, Lynnette; Knych, Heather; Cole, Gretchen; D'Agostino, Jennifer

    2016-06-01

    The objective of this study was to investigate the pharmacokinetics of a long-acting fentanyl solution in helmeted guineafowl ( Numida meleagris ) after transdermal administration. Twenty-one guineafowl received a single administration of 5 mg/kg of fentanyl transdermal solution. No adverse effects on behavior were appreciated. Plasma fentanyl concentrations were determined by liquid chromatography-mass spectrometry analysis of protein-precipitated samples. Mean maximum plasma concentration was 228.8 ng/ml at 4 hr. The mean plasma terminal half-life was 33.2 hr. At 168 hr the mean plasma concentration was 1.3 ng/ml. A single topical dose of 5 mg/kg appears to be safe for use in this species and maintained plasma concentrations above those reported to be analgesic in dogs for at least 7 days. PMID:27468018

  9. Pharmacodynamic actions of a long-acting PTH analog (LA-PTH) in thyroparathyroidectomized (TPTX) rats and normal monkeys

    PubMed Central

    Shimizu, Masaru; Joyashiki, Eri; Noda, Hiroshi; Watanabe, Tomoyuki; Okazaki, Makoto; Nagayasu, Miho; Adachi, Kenji; Tamura, Tatsuya; Potts, John T.; Gardella, Thomas J.; Kawabe, Yoshiki

    2016-01-01

    Hypoparathyroidism is a disease of chronic hypocalcemia and hyperphosphatemia due to a deficiency of parathyroid hormone (PTH). PTH and analogs of the hormone are of interest as potential therapies. Accordingly, we examined the pharmacological properties of a long-acting PTH analog, [Ala1,3,12,18,22, Gln10,Arg11,Trp14,Lys26]-PTH(1–14)/PTHrP(15–36) (LA–PTH) in thyroparathyroidectomized (TPTX) rats, a model of HP, as well as in normal monkeys. In TPTX rats, a single intra-venous administration of LA-PTH at a dose of 0.9 nmol/kg increased serum calcium (sCa) and decreased serum phosphate (sPi) to near-normal levels for longer than 48 hours, while PTH(1–34) and PTH(1–84), each injected at a dose 80-fold higher than that used for LA-PTH, increased sCa and decreased sPi only modestly and transiently (< 6 hours). LA-PTH also exhibited enhanced and prolonged efficacy versus PTH(1–34) and PTH(1–84) for elevating sCa when administered subcutaneously (SC) into monkeys. Daily SC administration of LA-PTH (1.8 nmol/kg) into TPTX rats for 28-days elevated sCa to near normal levels without causing hypercalciuria or increasing bone resorption markers, a desirable goal in the treatment of hypoparathyroidism. The results are supportive of further study of long-acting PTH analogs as potential therapies for patients with hypoparathyroidism. PMID:26865415

  10. Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients.

    PubMed

    Neggers, Sebastian J C M M; de Herder, Wouter W; Feelders, Richard A; van der Lely, A J

    2011-09-01

    The efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the individual beneficial and adverse effects, in two acromegaly patients, who only normalized their insulin like growth factor (IGF-I) levels with high-dose pegvisomant therapy. We present two cases of a 31 and 44 years old male with gigantism and acromegaly that were controlled subsequently by surgery, radiotherapy, SRIF analogs and daily PEG-V treatment. They were converted to combined treatment of monthly SSA and (twice) weekly PEG-V. High dose SSA treatment was added while the PEG-V dose was decreased during carful monitoring of the IGF-I. After switching from PEG-V monotherapy to SRIF analogs plus pegvisomant combination therapy IGF-I remained normal. However, the necessary PEG-V dose, to normalize IGF-I differed significantly between these two patients. One patient needed twice weekly 100 mg, the second needed 60 mg once weekly on top of their monthly lanreotide Autosolution injections of 120 mg. The weekly dose reduction was 80 and 150 mg. After the introducing of lanreotide, fasting glucose and glycosylated haemoglobin concentrations increased. Diabetic medication had to be introduced or increased. No changes in liver tests or in pituitary adenoma size were observed. In these two patients, PEG-V in combination with long-acting SRIF analogs was as effective as PEG-V monotherapy in normalizing IGF-I levels, although significant dose-reductions in PEG-V could be achieved. However, there seems to be a wide variation in the reduction of PEG-V dose, which can be obtained after conversion to combined treatment. PMID:21221818

  11. Long-acting methylphenidate reduces collision rates of young adult drivers with attention-deficit/hyperactivity disorder.

    PubMed

    Cox, Daniel J; Davis, Margaret; Mikami, Amori Yee; Singh, Harsimran; Merkel, Richard L; Burket, Roger

    2012-04-01

    This study investigated whether methylphenidate delivered through a long-acting transdermal system (MTS) would reduce collision rates of young adult drivers with attention-deficit/hyperactivity disorder (ADHD).Seventeen young adults completing the study (mean [SD] age, 20.82 [2.40] years; 14 men and 13 white) met the following inclusion criteria: ADHD diagnoses but not routinely taking ADHD medication, previously responsive to ADHD medication, active drivers with more than 1 collision or citation in the past 2 years, and no significant comorbidities. In this open-labeled, crossover design drivers were randomly assigned either to the no-medication condition for 3 months and then MTS for 3 months or to the reverse sequence. In-car video monitoring of routine driving occurred during these 6 months. At baseline and after each condition, participants completed the Conners Adult ADHD Rating Scale and the Cox Assessment of Risky Driving Scale, and their blood pressure, heart rate, and body weight were monitored.Compared with the no-medication condition, participants in the MTS condition self-reported fewer total ADHD (P < 0.04) and inattentive symptoms (P = 0.014) and a trend for risky driving behaviors (P = 0.059) and had fewer video-recorded collisions (P < 0.005) and other problematic driving events. There were no significant changes in blood pressure, heart rate, or body weight across conditions or any significant skin reactions to the MTS patch.This is the first study demonstrating that long-acting methylphenidate improves activities of daily living among young adults with ADHD. Specifically, methylphenidate improved safety in routine driving while reducing ADHD symptoms with minimal adverse effects. PMID:22367664

  12. Your Muscles

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Your Muscles KidsHealth > For Kids > Your Muscles Print A A ... and skeletal (say: SKEL-uh-tul) muscle. Smooth Muscles Smooth muscles — sometimes also called involuntary muscles — are ...

  13. Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions

    PubMed Central

    Little, Peter J; Osman, Narin; de Dios, Stephanie T; Cemerlang, Nelly; Ballinger, Mandy; Nigro, Julie

    2007-01-01

    Background Inhibition of vascular smooth muscle cell (vSMC) proliferation by oral anti-hyperglycemic agents may have a role to play in the amelioration of vascular disease in diabetes. Thiazolidinediones (TZDs) inhibit vSMC proliferation but it has been reported that they anomalously stimulate [3H]-thymidine incorporation. We investigated three TZDs, two biguanides and two sulfonylureas for their ability of inhibit vSMC proliferation. People with diabetes obviously have fluctuating blood glucose levels thus we determined the effect of media glucose concentration on the inhibitory activity of TZDs in a vSMC preparation that grew considerably more rapidly under high glucose conditions. We further explored the mechanisms by which TZDs increase [3H]-thymidine incorporation. Methods VSMC proliferation was investigated by [3H]-thymidine incorporation into DNA and cell counting. Activation and inhibition of thymidine kinase utilized short term [3H]-thymidine uptake. Cell cycle events were analyzed by FACS. Results VSMC cells grown for 3 days in DMEM with 5% fetal calf serum under low (5 mM glucose) and high (25 mM glucose) increased in number by 2.5 and 4.7 fold, respectively. Rosiglitazone and pioglitazone showed modest but statistically significantly greater inhibitory activity under high versus low glucose conditions (P < 0.05 and P < 0.001, respectively). We confirmed an earlier report that troglitazone (at low concentrations) causes enhanced incorporation of [3H]-thymidine into DNA but did not increase cell numbers. Troglitazone inhibited serum mediated thymidine kinase induction in a concentration dependent manner. FACS analysis showed that troglitazone and rosiglitazone but not pioglitazone placed a slightly higher percentage of cells in the S phase of a growing culture. Of the biguanides, metformin had no effect on proliferation assessed as [3H]-thymidine incorporation or cell numbers whereas phenformin was inhibitory in both assays albeit at high concentrations

  14. Factors affecting women’s intention to use long acting and permanent contraceptive methods in Wolaita Zone, Southern Ethiopia: A cross-sectional study

    PubMed Central

    2014-01-01

    Background The use of long acting and permanent contraceptive methods (LAPMs) has not kept step with that of short-acting methods such as oral pills and injectable in Africa. This study explores the association between women’s awareness, attitude and barriers with their intention to use LAPMs among users of short term methods, in Southern Ethiopia. Methods A cross-sectional study design of mixed methods was conducted in the public health facilities of Wolaita zone, Southern Ethiopia, in January 2013. Women who were using short term contraceptive methods were the study population (n = 416). Moreover, 12 in-depth interviews were conducted among family planning providers and women who have been using short term methods. Data were entered into EPI Info version 3.5.3 and exported to SPSS version 16.0 for analysis. The odds ratios in the binary logistic regression model along with 95% confidence interval were used. Results One hundred fifty six (38%) of women had the intention to use LAPMs while nearly half of them (n = 216) had a negative attitude to use such methods. Moreover, two-third of study participants (n = 276) held myths and misconceptions about such methods. The women who had a positive attitude were found to be 2.5 times more intention to use LAPMs compared to women who had a negative attitude (AOR =2. 47; 95% CI: 1.48- 4.11). Women who had no myths and misconceptions on LAPMs were found to be 1.7 times more intention to use LAPMs compared to women who had myths and misconceptions (AOR = 1.71; 95% CI: 1.08- 2.72). Likewise, women who attained secondary and higher level of education were found to be 2 and 2.8 times more intention to use LAPMs compared to women with no education, respectively (AOR = 2. 10; 95% CI: 1.11- 3.98) and AOR = 2. 80; 95% CI: 1.15- 6.77). Conclusions Intention to use LAPMs was low and nearly half of women had a negative attitude to use such methods. Positive attitude, absence of myths and misconceptions on

  15. Comparative effects of long-acting and short-acting loop diuretics on cardiac sympathetic nerve activity in patients with chronic heart failure

    PubMed Central

    Matsuo, Yae; Kasama, Shu; Toyama, Takuji; Funada, Ryuichi; Takama, Noriaki; Koitabashi, Norimichi; Ichikawa, Shuichi; Suzuki, Yasuyuki; Matsumoto, Naoya; Sato, Yuichi; Kurabayashi, Masahiko

    2016-01-01

    Objective Short-acting loop diuretics are known to enhance cardiac sympathetic nerve activity (CSNA) in patients with chronic heart failure (CHF). The effects of two loop diuretics—long-acting azosemide and short-acting furosemide—on CSNA were evaluated using 123I-metaiodobenzylguanidine (MIBG) scintigraphy in patients with CHF. Methods The present study was a subanalysis of our previously published study, which had reported that serial 123I-MIBG studies were the most useful prognostic indicator in patients with CHF. Patients with CHF (n=208, left ventricular ejection fraction <45%) but no history of cardiac events for at least 5 months prior to the study were identified according to their histories of acute decompensated heart failure requiring hospitalisation. Patients underwent 123I-MIBG scintigraphy immediately before hospital discharge and at a 6-month follow-up. The delayed % denervation, delayed heart/mediastinum count (H/M) ratio and washout rate (WR) were determined using 123I-MIBG scintigraphy. A total of 108 patients were selected, and propensity score matching was used to compare patients treated with either oral azosemide (n=54) or furosemide (n=54). Results After treatment, 123I-MIBG scintigraphic parameters improved in both groups. However, the degree of change in % denervation was −13.8±10.5 in the azosemide group and −5.7±12.7 in the furosemide group (p<0.01), the change in H/M ratio was 0.20±0.16 in the azosemide group and 0.06±0.19 in the furosemide group (p<0.01), and the change in WR was −11.3±9.2% in the azosemide group and −3.0±12.7% in the furosemide group (p<0.01). Moreover, multivariate analysis showed an independent and significant positive relationship between furosemide and δ-WR from hospital discharge to 6 months after treatment in patients with CHF (p=0.001). Conclusions These findings indicate that azosemide suppresses CSNA compared with furosemide in patients with CHF. Trial registration number UMIN000000626

  16. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus.

    PubMed

    Berard, Lori; MacNeill, Gail

    2015-02-01

    Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes.

  17. Working with State Health Departments on Emerging Issues in Maternal and Child Health: Immediate Postpartum Long-Acting Reversible Contraceptives

    PubMed Central

    Kroelinger, Charlan D.; Waddell, Lisa F.; Goodman, David A.; Pliska, Ellen; Rudolph, Claire; Ahmed, Einas; Addison, Donna

    2016-01-01

    Background Immediate postpartum long-acting reversible contraceptives (LARC) are highly effective in preventing unintended pregnancy. State health departments are in the process of implementing a systems change approach to better apply policies supporting the use of immediate postpartum LARC. Methods Beginning in 2014, a group of national organizations, federal agencies, and six states have convened a LARC Learning Community to share strategies and best practices in immediate postpartum LARC policy development and implementation. Community activities consist of in-person meetings and a webinar series as forums to discuss systems change. Results The Learning Community identified eight domains for discussion and development of resources: training, pay streams, stocking and supply, consent, outreach, stakeholder partnerships, service location, and data and surveillance. The community is currently developing resource materials and guidance for use by other state health departments. Conclusions To effectively implement policies on immediate postpartum LARC, states must engage a number of stakeholders in the process, raise awareness of the challenges to implementation, and communicate strategies across agencies during policy development. PMID:26390378

  18. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

    PubMed Central

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

  19. Changes in methacholine induced bronchoconstriction with the long acting beta 2 agonist salmeterol in mild to moderate asthmatic patients.

    PubMed Central

    Booth, H.; Fishwick, K.; Harkawat, R.; Devereux, G.; Hendrick, D. J.; Walters, E. H.

    1993-01-01

    BACKGROUND--Beta-2 agonists protect against non-specific bronchoconstricting agents such as methacholine, but it has been suggested that the protection afforded by long acting beta 2 agonists wanes rapidly with regular treatment. METHODS--The changes in airway responsiveness were investigated during and after eight weeks of regular treatment with salmeterol 50 micrograms twice daily in 26 adult asthmatic patients, 19 of whom were receiving maintenance inhaled corticosteroids. The study was of a randomised, placebo controlled, double blind design. Airway responsiveness to methacholine was measured as PD20 by a standardised dosimeter technique 12 hours after the first dose, at four weeks and eight weeks during treatment (12 hours after the last dose of test medication), and at 60 hours, one week and two weeks after stopping treatment. RESULTS--There were no significant differences between the baseline characteristics of the two groups. A significant improvement in PD20 was seen at all points during treatment with salmeterol compared with the placebo group, with no significant fall off with time. PD20 measurements returned to baseline values after cessation of treatment with no significant difference from the placebo group. CONCLUSIONS--Salmeterol gave significant protection against methacholine induced bronchoconstriction 12 hours after administration. This protection was of small magnitude, but there was no significant attenuation with eight weeks of regular use and no rebound increase in airway responsiveness on stopping treatment in a group of moderate asthmatic patients, the majority of whom were receiving inhaled corticosteroids. PMID:8296255

  20. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy.

    PubMed

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory's development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

  1. [Pharmacodynamics and results of a clinical trial of nitrogranulong, a new Soviet long-acting preparation of nitroglycerin].

    PubMed

    Sokolov, S Ia; Belova, L F; Trumpe, T E; Alibekov, S D; Sakovich, G S; Rusakova, K A; Ivanov, A A; Belozerova, O P

    1990-10-01

    In the USSR, the Research and Production Association "Vitamins" and the Department of Pharmacology, All-Union Research Institute of Medicinal Plants were the first to develop commercial processes for manufacturing trinitroglycerol microgranules on the basis of the raw material available in this country and to design the new long-acting drug Nitrogranulong. Experimental examinations revealed that Nitrogranulong showed the same bioavailability as Nitro-Mack-Retard and sustac, produced a prolonged coronarolytic effect, and caused the hemodynamic and ECG changes typical of trinitroglycerol. The agent was found to be low toxic and well tolerated in a dosage form. Clinical examination of 467 patients indicated that Nitrogranulong exhibited the same antianginal potency, but in some cases it was superior to sustac, nitrong, 2% nitroglycerin ointment, and nitrosorbide. The agent caused significantly less adverse and toxic effects. Nitrogranulong is used in medical practice to prevent anginal episodes. It is produced in tablets in two dosages (2.9 and 5.2 mg trinitroglycerol), its action duration being 7-8 hours.

  2. Radioimmunoassay for octapeptide analogs of somatostatin: Measurement of serum levels after administration of long-acting microcapsule formulations

    SciTech Connect

    Mason-Garcia, M.; Vaccarella, M.; Horvath, J.; Redding, T.W.; Groot, K.; Orsolini, P.; Schally, A.V. )

    1988-08-01

    The development of a long-acting delivery system for D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH{sub 2} (RC-160), an octapeptide analog of somatostatin, required the establishment of a method for determining the concentration of this analog in serum during treatment. A sensitive and specific radioimmunoassay (RIA) for RC-160 was developed and used for following the rate of liberation of this peptide from microcapsules of poly(DL-lactide-coglycolide). Antibodies were generated in a rabbit against RC-160 conjugated to bovine serum albumin with glutaraldehyde. At an antiserum dilution of 1:100,000, the antibodies bound approximately 25% of added radiolabeled RC-160. Somatostatin octapeptide analogs that had a disulfide bridge showed crossreactivity with the antiserum, but analogs without the disulfide bridge and other peptides tested did not crossreact. The minimum detectable dose of RC-160 was 10 pg. Intra- and interassay coefficients of variation ranged from 9.1% to 12.8% and from 14% to 30%, respectively. The RIA was suitable for direct determination of RC-160 in serum. Eleven prototype batches of microcapsules were tested in rats, and the rate of release of the analog from the microcapsules was followed. An improved batch of microcapsules made from RC-160 pamoate maintained high serum levels of RC-160 for more than 30 days after intramuscular injection. The RIA should be of value for monitoring levels of this analog in serum during long-term therapy.

  3. Radioimmunoassay for octapeptide analogs of somatostatin: measurement of serum levels after administration of long-acting microcapsule formulations.

    PubMed Central

    Mason-Garcia, M; Vaccarella, M; Horvath, J; Redding, T W; Groot, K; Orsolini, P; Schally, A V

    1988-01-01

    The development of a long-acting delivery system for D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), an octapeptide analog of somatostatin, required the establishment of a method for determining the concentration of this analog in serum during treatment. A sensitive and specific radioimmunoassay (RIA) for RC-160 was developed and used for following the rate of liberation of this peptide from microcapsules of poly(DL-lactide-coglycolide). Antibodies were generated in a rabbit against RC-160 conjugated to bovine serum albumin with glutaraldehyde. At an antiserum dilution of 1:100,000, the antibodies bound approximately 25% of added radiolabeled RC-160. Somatostatin octapeptide analogs that had a disulfide bridge showed crossreactivity with the antiserum, but analogs without the disulfide bridge and other peptides tested did not crossreact. The minimum detectable dose of RC-160 was 10 pg. Intra- and interassay coefficients of variation ranged from 9.1% to 12.8% and from 14% to 30%, respectively. The RIA was suitable for direct determination of RC-160 in serum. Eleven prototype batches of microcapsules were tested in rats, and the rate of release of the analog from the microcapsules was followed. An improved batch of microcapsules made from RC-160 pamoate maintained high serum levels of RC-160 for more than 30 days after intramuscular injection. The RIA should be of value for monitoring levels of this analog in serum during long-term therapy. PMID:2899894

  4. Can a new ultra-long-acting insulin analogue improve patient care? Investigating the potential role of insulin degludec.

    PubMed

    Robinson, Jennifer D; Neumiller, Joshua J; Campbell, R Keith

    2012-12-24

    The basal-bolus concept of delivering insulin to diabetic patients makes physiological sense, as it mimics normal insulin release in people without diabetes. In line with this concept, a major effort put forth by insulin manufacturers has been to develop the ideal exogenous basal insulin product. The perfect basal insulin product would be injected into subcutaneous tissue without causing irritation, release insulin continuously at a constant rate for at least 24 hours, be stable, not contribute to weight gain, have a low risk of allergic reactions and, very importantly, minimize the risk of hypoglycaemia. While the perfect insulin has not yet been discovered, advancements are still being made. Insulin degludec is an ultra-long-acting basal insulin analogue that possesses a flat, stable glucose-lowering effect in patients with type 1 or type 2 diabetes mellitus. Insulin degludec achieves these pharmacokinetic properties by forming soluble multihexamers upon subcutaneous injection, resulting in the formation of a depot in the subcutaneous tissue that is slowly released and absorbed into circulation. Insulin degludec has been associated with slightly less weight gain and fewer nocturnal hypoglycaemic episodes when compared with insulin glargine in some, but not all, clinical studies. This article briefly reviews current evidence for the use of insulin degludec in patients with type 1 or type 2 diabetes mellitus and discusses the potential impact of this new basal insulin on clinical practice. PMID:23145524

  5. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus.

    PubMed

    Berard, Lori; MacNeill, Gail

    2015-02-01

    Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes. PMID:25065475

  6. Long-acting paliperidone palmitate – interim results of an observational study of its effect on hospitalization

    PubMed Central

    Olofinjana, Olubanke

    2014-01-01

    Paliperidone palmitate (PP) is a recently introduced long-acting atypical, or second-generation, antipsychotic. Published data on PP are currently limited to controlled trials and case reports. In this observational study, we followed up 200 consecutive patients prescribed PP in normal practice. After 1 year, 65% of patients were still receiving PP. The number of admissions to hospital in the year following PP initiation was 0.49/patient compared with 0.69/patient/year, 3 years before initiation (P=0.0001). The mean number of bed days fell from 38.78 to 23.09/patient/year over the corresponding period (P=0.0001). The median number of bed days 3 years before PP initiation was 21.50/year and in the year following PP initiation, it was 0. Outcomes were numerically but not statistically better in those continuing PP than in those who ceased PP within a year of initiation. PP was effective and well-tolerated and, given its positive effect on hospital bed days, broadly cost-effective. PMID:24419004

  7. Evolution of opioid risk management and review of the classwide REMS for extended-release/long-acting opioids.

    PubMed

    Stanos, Steven

    2012-11-01

    In 2007, the Food and Drug Administration Amendments Act (FDAAA) afforded the US Food and Drug Administration (FDA) the ability to enforce postmarketing risk management strategies for prescription medicines. Under this policy, certain medications with known or potential risks could be required to have a Risk Evaluation and Mitigation Strategy (REMS), a risk management program designed to ensure that a product's therapeutic benefit outweighs its risks. Prescription opioid analgesics, particularly extended-release (ER)/long-acting (LA) formulations, have undergone scrutiny in recent years due to the serious risks associated with their use, especially when they are prescribed improperly, misused, or abused. In July 2012, the FDA approved a classwide REMS for ER and LA opioids. This ER/LA opioid REMS program is designed to improve prescriber education and patient awareness about safe opioid use to minimize the risks of addiction, unintentional overdose, and death. Because clinicians often encounter patients with moderate-to-severe chronic, noncancer pain who are in need of around-the-clock opioid analgesia, knowledge of the conditions of this classwide REMS may become essential to continue prescribing ER/LA opioids. This article briefly describes the changes in US risk management policies that have shaped today's regulatory environment and provides an overview of the requirements for the classwide ER/LA opioid REMS.

  8. Recombinant factor VIIa reverses the anticoagulant effect of the long-acting pentasaccharide idraparinux in healthy volunteers.

    PubMed

    Bijsterveld, Nick R; Vink, Roel; van Aken, Benien E; Fennema, Hein; Peters, Ron J G; Meijers, Joost C M; Büller, Harry R; Levi, Marcel

    2004-03-01

    We investigated whether the anticoagulant effect of idraparinux, a selective long-acting factor Xa inhibitor, could be neutralized by recombinant factor VIIa (rFVIIa) in healthy male volunteers. We performed a randomized, placebo-controlled trial, comparing idraparinux [7.5 mg subcutaneous (s.c.)] followed at 3 h by rFVIIa [90 microg/kg intravenous (i.v.)] (n = 6), or idraparinux (7.5 mg s.c) followed after 1 week by rFVIIa (90 microg/kg i.v.)(n = 6). rFVIIa, given 3 h after idraparinux, significantly reversed the increased thrombin generation time (TGT), the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT), and the reduced prothrombin fragment 1+2 (F1+2) levels caused by idraparinux, although no clear effect of rFVIIa on the endogenous thrombin potential (ETP) was observed. One week after idraparinux, injection of rFVIIa resulted in a similar relative reduction of the remaining increased aPTT, PT and TGT, with correction to pre-idraparinux values. A clear increase of F1+2 was observed, together with a small increase in ETP. We conclude that rFVIIa has significant effects on the idraparinux-inhibited thrombin generation and clotting parameters. These results suggest that rFVIIa may be useful in serious bleeding complications in idraparinux treated patients.

  9. Effects of a long-acting, trace mineral, reticulorumen bolus on range cow productivity and trace mineral profiles.

    PubMed

    Sprinkle, J E; Cuneo, S P; Frederick, H M; Enns, R M; Schafer, D W; Carstens, G E; Daugherty, S B; Noon, T H; Rickert, B M; Reggiardo, C

    2006-06-01

    The objectives were to determine if strategic supplementation of range cows with a long-acting (6 mo), trace mineral, reticulorumen bolus containing Cu, Se, and Co would: (1) increase cow BCS and BW, and calf birth, weaning, and postweaning weights, or weight per day of age (WDA); (2) increase liver concentrations of Cu or Zn in cows, or blood Se, Cu, or Zn concentrations in cows and calves; and (3) vary by cow breed for any of these response variables. There were 192 control and 144 bolused Composite cows (C; 25% Hereford, Angus, Gelbevieh, and Senepol or Barzona); 236 control and 158 bolused Hereford (H) cows; and 208 control and 149 bolused Brahman cross (B) cows used in a 3-yr experiment. Cows were weighed and scored for body condition in January, May, and September, and all bolused cows received boluses in January. Each year, from among the 3 breed groups a subset of 15 control and 15 bolused cows (n = 90) had samples obtained in January and May for liver Cu and Zn, blood Se, and serum Cu and Zn. As for cows, blood and serum from the calves of these cows were sampled each year in May and September for Cu, Se, and Zn. There was a significant breed x year x treatment interaction (P = 0.001) for cow weight loss from January to May. Calf WDA, weaning, and postweaning weights did not differ (P > 0.40) between bolused and control cows, but there was a significant (P = 0.022) breed x year x treatment interaction for birth weight. Liver Cu was deficient (< 75 ppm; P < 0.001) in control cows and adequate (< 75 to 90 ppm) for bolused cows. Liver Cu differed by year (P < 0.001). Blood Se was adequate (< 0.1 ppm) for all cows except in January 2001 and 2002. There was no difference (P > 0.50) in blood Se between treatment groups in January, but bolused cows had greater (P < 0.01) blood Se in May. Breed differences for blood Se concentrations existed for bolused cows, with B having greater (P < 0.05) blood Se than either C or H cows. Breed differences also existed for

  10. Pharmacokinetics and the effect of application site on a novel, long-acting transdermal fentanyl solution in healthy laboratory Beagles.

    PubMed

    Freise, K J; Newbound, G C; Tudan, C; Clark, T P

    2012-08-01

    Application of transdermal drugs to different anatomical sites can result in different absorption characteristics. The pharmacokinetics (PKs) and bioequivalence of a single 2.6 mg/kg (50 μL/kg) dose of a novel, long-acting transdermal fentanyl solution were determined when applied topically to the ventral abdominal or dorsal interscapular skin of 40 healthy laboratory Beagles. The PKs were differentiated by a more rapid initial absorption of fentanyl from the dorsal application site. Mean plasma fentanyl concentrations remained above 0.6 ng/mL from 4 to 96 h in the dorsal application group and from 8 to 144 h in the ventral application group. Bioequivalence analysis demonstrated that the sites were not equivalent; the 90% confidence intervals of the ratio of the geometric means for both the maximum concentration (C(max)) and the area under the curve (AUC) were not contained within the 80-125% interval. The C(max) was 2.34 ± 1.29 (mean ± standard deviation) and 2.02 ± 0.84 ng/mL for the ventral and dorsal application groups, respectively. The terminal elimination half-lives (t(1/2)) for both groups were similar with values of 137 ± 58.9 and 117 ± 59.6 h for the ventral and dorsal application site groups, respectively. A mean absorption rate of ≥ 2 μg · kg/h was maintained from 2 to 144 h following dorsal application and from 2 to 264 h following ventral application. These results suggest that transdermal fentanyl solution could be applied as a single dose to the dorsal scapular area 2-4 h prior to surgery with analgesia lasting a minimum of 4 days.

  11. A Controlled, Evidence-Based Trial of Paliperidone Palmitate, A Long-Acting Injectable Antipsychotic, in Schizophrenia

    PubMed Central

    Nasrallah, Henry A; Gopal, Srihari; Gassmann-Mayer, Cristiana; Quiroz, Jorge A; Lim, Pilar; Eerdekens, Mariëlle; Yuen, Eric; Hough, David

    2010-01-01

    Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set (N=514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50 mg equiv., p=0.02; 100 mg equiv., p<0.001), as well as Clinical Global Impression Severity scores (p⩽0.006) and PANSS negative and positive symptom Marder factor scores (p⩽0.04). The Personal and Social Performance scale showed no significant difference between treatment groups. The overall incidence of treatment-emergent adverse events was similar between groups. Parkinsonism, the most frequently reported extrapyramidal symptom, was reported at similar rates for placebo (5%) and paliperidone palmitate (5–6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. Investigator-evaluated injection-site pain, swelling, redness, and induration were similar across treatment groups; scores for patient-evaluated injection-site pain (visual analog scale) were similar across groups and diminished with time. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia. PMID:20555312

  12. Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein.

    PubMed

    McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

    2014-07-01

    Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc.

  13. Efficacy of octreotide long-acting repeatable in neuroendocrine tumors: RADIANT-2 placebo arm post hoc analysis

    PubMed Central

    Strosberg, Jonathan R; Yao, James C; Bajetta, Emilio; Aout, Mounir; Bakker, Bert; Hainsworth, John D; Ruszniewski, Philippe B; Van Cutsem, Eric; Öberg, Kjell; Pavel, Marianne E

    2015-01-01

    Somatostatin analogues (SSA) have demonstrated antiproliferative activity in addition to efficacy for carcinoid symptom control in functional neuroendocrine tumors (NET). A post hoc analysis of the placebo arm of the RAD001 In Advanced Neuroendocrine Tumors-2 (RADIANT-2) study was conducted to assess the efficacy of octreotide long-acting repeatable (LAR) on progression-free survival (PFS) and overall survival (OS) estimated using the Kaplan–Meier method. Out of 213 patients randomized to placebo plus octreotide LAR in RADIANT-2, 196 patients with foregut, midgut, or hindgut NET were considered for present analysis. Of these, 41 patients were SSA-treatment naïve and 155 had received SSA therapy before study entry. For SSA-naïve patients, median PFS by adjudicated central review was 13.6 (95% CI 8.2–22.7) months. For SSA-naïve patients with midgut NET (n=24), median PFS was 22.2 (95% CI 8.3–29.5) months. For patients who had received SSA previously, the median PFS was 11.1 (95% CI 8.4–14.3) months. Among the SSA-pretreated patients who had midgut NET (n=119), the median PFS was 12.0 (95% CI 8.4–19.3) months. Median OS was 35.8 (95% CI 32.5–48.9) months for patients in the placebo plus octreotide LAR arm; 50.6 (36.4 – not reached) months for SSA-naïve patients and 33.5 (95% CI 27.5–44.7) months for those who had received prior SSA. This post hoc analysis of the placebo arm of the large phase 3 RADIANT-2 study provides data on PFS and OS among patients with progressive NET treated with octreotide therapy. PMID:26373569

  14. Safety, pharmacokinetic and pharmacodynamic properties of TV-1106, a long-acting GH treatment for GH deficiency

    PubMed Central

    Cohen-Barak, Orit; Sakov, Anat; Rasamoelisolo, Michele; Bassan, Merav; Brown, Kurt; Mendzelevski, Boaz; Spiegelstein, Ofer

    2015-01-01

    Background TV-1106 (Teva Pharmaceuticals) is a genetically fused recombinant protein of human GH (hGH) and human serum albumin, in development for treatment of GH deficiency (GHD). TV-1106 is expected to have an extended duration of action compared to daily GH treatment and may enable a reduction in the frequency of injections and improve compliance and quality of life for adults and children requiring GHD therapy. Objective To assess the safety, local tolerability, pharmacokinetics and pharmacodynamics of TV-1106 following single s.c. injections in healthy male volunteers. Methods Subjects (n=56) were assigned to one of seven ascending dose groups (3–100 mg) and received either a single dose of TV-1106 (n=6) or placebo (n=2) by s.c. injection. Results Eighteen subjects reported 43 adverse effects (AEs), which were mild to moderate; no serious AEs (SAEs) occurred. In 50, 70 and 100 mg groups there were mild to moderate increases in heart rate and systolic blood pressure that significantly correlated with higher levels of IGF1. TV-1106 showed pharmacokinetic characteristics of a long-acting hGH as demonstrated by a terminal elimination half-life of 23–35 h, delayed time of peak concentration, and systemic levels seen up to 7 days after dosing. IGF1 levels increased in a dose-dependent manner, before reaching a plateau, with levels above baseline extending beyond 7 days post dose. Conclusion Single administration of TV-1106 up to 100 mg was safe in healthy volunteers. Pharmacokinetics and pharmacodynamics support once-weekly administration in patients with GHD. PMID:26286586

  15. Investigation of salt formation between memantine and pamoic acid: Its exploitation in nanocrystalline form as long acting injection.

    PubMed

    Mittapelly, Naresh; Rachumallu, Ramakrishna; Pandey, Gitu; Sharma, Shweta; Arya, Abhishek; Bhatta, Rabi Shankar; Mishra, Prabhat Ranjan

    2016-04-01

    In the present work, we prepared memantine-pamoic acid (MEM-PAM) salt by counter ion exchange in the aqueous phase to reduce the water solubility of MEM hydrochloride (native form) to make it suitable for long acting injection. The ratio of MEM to PAM in salt formation was optimized to maximize the loading efficiency and complexation efficiency. The 2:1 molar ratio of MEM to PAM salt form displayed nearly 95% complexation efficiency and 50% drug loading. The solubility was decreased by a ∼1250 folds. Thermo Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction Analysis (PXRD) studies revealed the formation of new solid phase. Additionally, Nuclear Magnetic Resonance (NMR) spectroscopy confirmed the anhydrous nature of the salt form. Through Fourier transformation infrared spectroscopy (FT-IR) we identified the molecular interactions. Further, the microcrystals of the salt were transformed into nanocrystals (NCs) using high pressure homogenization. The particle size distribution and atomic force microscopy confirmed the monodispersed and spherical shape of the NCs. The in vitro dissolution studies were performed under sink condition in phosphate buffer saline pH 6.8. The results of MTT assay in murine fibroblast 3T3 cell line show that the NCs were less cytotoxic and more tolerable than plain MEM HCl. The in vivo performance of NCs administered as i.m. injection at three different doses in female Sprague-Dawley rats showed that the plasma levels lasted till the 24th day of the study. The pharmacokinetic parameters AUC0-∞ and Cmax increased linearly with increasing dose. Therefore, the results suggest that injectable NCs could represent a therapeutic alternative for the treatment of AD. PMID:26850817

  16. Amelioration of the cardiovascular effects of cocaine in rhesus monkeys by a long-acting mutant form of cocaine esterase.

    PubMed

    Collins, Gregory T; Carey, Kathy A; Narasimhan, Diwahar; Nichols, Joseph; Berlin, Aaron A; Lukacs, Nicholas W; Sunahara, Roger K; Woods, James H; Ko, Mei-Chuan

    2011-04-01

    A long-acting mutant form of a naturally occurring bacterial cocaine esterase (T172R/G173Q CocE; double mutant CocE (DM CocE)) has previously been shown to antagonize the reinforcing, convulsant, and lethal effects of cocaine in rodents. However, the effectiveness and therapeutic characteristics of DM CocE in nonhuman primates, in a more clinically relevant context, are unknown. The current studies were aimed at (1) characterizing the cardiovascular effects of cocaine in freely moving rhesus monkeys, (2) evaluating the capacity of DM CocE to ameliorate these cocaine-induced cardiovascular effects when administered 10 min after cocaine, and (3) assessing the immunological responses of monkeys to DM CocE following repeated administration. Intravenous administration of cocaine produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR) that persisted throughout the 2-h observation period following a dose of 3.2 mg/kg cocaine. Cocaine failed to produce reliable changes in electrocardiograph (ECG) parameters, body temperature, and locomotor activity. DM CocE produced a rapid and dose-dependent amelioration of the cardiovascular effects, with saline-like MAP measures restored within 5-10 min, and saline-like HR measures restored within 20-40 min of DM CocE administration. Although administration of DM CocE produced increases in anti-CocE antibodies, they did not appear to have a neutralizing effect on the capacity of DM CocE to reverse the cardiovascular effects of cocaine. In conclusion, these findings in monkeys provide strong evidence to suggest that highly efficient cocaine esterases, such as DM CocE, can provide a potential therapeutic option for treatment of acute cocaine intoxication in humans. PMID:21289605

  17. HelpDesk answers: is it safe to add long-acting β-2 agonists to inhaled corticosteroids in patients with persistent asthma?

    PubMed

    Townsend, Laurie; Madlon-Kay, Diane J

    2015-06-01

    Possibly. Long-acting β-2 agonists (LABAs) used in combination with inhaled corticosteroids (ICS) don't appear to increase all-cause mortality or serious adverse events in patients with persistent asthma compared with ICS alone. Studies showing an increase in catastrophic events had serious methodologic issues. A large surveillance study is ongoing.

  18. The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle.

    PubMed Central

    Van Donkersgoed, J; VanderKop, M; Salisbury, C; Sears, L; Holowath, J

    1999-01-01

    Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter. The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site. PMID:12001341

  19. Determinants of long acting and permanent contraceptive methods utilization among married women of reproductive age groups in western Ethiopia: a cross-sectional study

    PubMed Central

    Melka, Alemu Sufa; Tekelab, Tesfalidet; Wirtu, Desalegn

    2015-01-01

    Introduction In Ethiopia information on the level of utilization of the long term and permanent contraceptive methods and associated factorsis lacking. The aim of this study was to understand the determinant factors of long acting and permanent contraceptive methods use among married women of reproductive age in Western Ethiopia. Methods A community based cross- sectional study design was employed. Multi stage sampling was used to select 1003 study participants. Data was collected from April 10 to April 25,2014 using a pre- tested structured questionnaire. The data were entered using Epi-info version 3.5.1 and exported to SPSS version 20 for analysis. Multivariate logistic regression analysis was done to identify predictors of long acting and permanent contraceptive methods at 95% CL. Results Use of long acting and permanent contraceptive methods in this study was found to be 20%. Survey results showed a significant positive association between utilization of long acting and permanent contraceptive methods and women's education (AOR = 1.72, 95%CI = 1.02 - 3.05), women's occupation (AOR = 2.01, 95% CI = 1.11 -3.58), number of live children (AOR = 2.42, 95% CI: 1.46- 4.02), joint fertility related decision (AOR = 6.11, 95% CI: 2.29- 16.30), having radio/TV (AOR = 2.31, 95% CI: 1.40 - 3.80), and discussion with health care provider about long acting and permanent contraceptive methods (AOR = 13.72, 95% CI: 8.37 - 22.47). Conclusion Efforts need to be aimed at women empowerment, health education, and encouraging open discussion of family planning by couples PMID:26523185

  20. Long-acting somatostatin analogues provide significant beneficial effect in patients with refractory small bowel angiodysplasia: Results from a proof of concept open label mono-centre trial

    PubMed Central

    Hall, Barry; Breslin, Niall; McNamara, Deirdre

    2015-01-01

    Introduction Small bowel angiodysplasias account for over 50% of causes of small bowel bleeding and carry a worse prognosis than lesions located elsewhere in the gastrointestinal tract. Re-bleeding rates are high even after first-line endoscopic therapy and are associated with high levels of morbidity for affected patients. Small trials of long-acting somatostatin analogues have shown promising results but have not yet been assessed in patients with refractory small bowel disease. Aim The purpose of this study was to assess the effect of long-acting somatostatin analogues in reducing re-bleeding rates and transfusion requirements, and improving haemoglobin levels in patients with refractory small bowel angiodysplasia. Methods Patients with refractory small bowel angiodysplasia were treated with 20 mg of long-acting octreotide for a minimum of three months. Response was assessed according to: rates of re-bleeding, haemoglobin levels, transfusion requirements, and side effects. Results A total of 24 patients were initially treated and 20 received at least three doses. Rates of complete, partial and non-response were 70%, 20% and 10% respectively. Average haemoglobin rates increased from 9.19 g/dl to 11.35 g/dl (p = 0.0027, 95% confidence interval (CI) −3.5 to −1.1) in the group overall and 70% remained transfusion-free after a mean treatment duration of 8.8 months. The rate of adverse events was higher than previously reported at 30%. Conclusion Long-acting somatostatin analogues offer a therapeutic advantage in a significant proportion of patients with small bowel angiodysplasia. With careful patient selection and close observation, a long-acting somatostatin analogue should be considered in all patients with persistent anaemia attributable to refractory disease in conjunction with other standard treatments. PMID:26966525

  1. Changes in Use of Long-Acting Reversible Contraceptive Methods Among U.S. Women, 2009–2012

    PubMed Central

    Kavanaugh, Megan L.; Jerman, Jenna; Finer, Lawrence B.

    2016-01-01

    OBJECTIVE To examine current levels, current correlates of, and changes in long-acting reversible contraceptive (LARC) use, including intrauterine devices and implants, among females aged 15–44 years using contraception between 2008–2010 and 2011–2013 with specific attention to associations between race, income, and age and their LARC use. METHODS We analyzed data from two rounds of the National Survey of Family Growth, nationally representative samples of females aged 15–44 years, consisting of 6,428 females in 2008–2010 and 5,601 females in 2011–2013. We conducted simple and multivariable logistic regression analyses with adjustments for the sampling design to identify demographic characteristics predictive of LARC use and changes in these patterns between the two time periods. In this cross-sectional, descriptive study, our primary outcome of interest was current prevalence of LARC use among all contraceptive users at the time of the interview. RESULTS The prevalence of LARC use among contracepting U.S. females increased from 8.5% in 2009 to 11.6% in 2012 (P<.01). The most significant increases occurred among Hispanic females (from 8.5% to 15.1%), those with private insurance (7.1–11.1%), those with fewer than two sexual partners in the previous year (9.2–12.4%), and those who were nulliparous (2.1–5.9%) (all P<.01). In multivariable analyses adjusting for key demographic characteristics, the strongest associations with LARC use in 2012 were parity (adjusted odds ratios [ORs] 4.3–5.5) and having a history of stopping non-LARC hormonal use (adjusted OR 1.9). Women aged 35–44 years (adjusted OR 0.3) were less likely to be LARC users than their counterparts (all P<.001). Poverty status was not associated with LARC use. There were no differences in discontinuation of LARC methods resulting from dissatisfaction between minority women and non-Hispanic white women. CONCLUSION During the most recent time period surveyed, use of LARC methods

  2. Combined inhaled corticosteroid and long-acting β2-adrenergic agonist therapy for noncystic fibrosis bronchiectasis with airflow limitation

    PubMed Central

    Wei, Ping; Yang, Jia-Wei; Lu, Hai-Wen; Mao, Bei; Yang, Wen-Lan; Xu, Jin-Fu

    2016-01-01

    Abstract Background and objective: There is presently no clear evidence on the effect of combined treatment for non-cystic fibrosis (non-CF) bronchiectasis with inhaled corticosteroid (ICS) and long-acting β2-adrenergic agonist (LABA). The objective of this study is to assess the efficacy and safety of salmeterol-fluticasone combined inhaled therapy for non-CF bronchiectasis with airflow limitation. Methods: An observational study was performed in 120 non-CF bronchiectasis patients diagnosed by high-resolution computed tomography (HRCT) scanning of the chest. Patients received either routine therapy or salmeterol-fluticasone (100/500 μg daily) combined inhaled therapy on the basis of routine therapy. Clinical symptoms, health-related quality of life (HRQL), lung function, short-acting β2-adrenergic agonist (SABA) use, and safety were monitored throughout the study. Results: OF the 120 subjects, 60 received combined inhaled therapy and 60 received routine therapy. Compared to the control group, the combined inhaled therapy group showed significant improvement in their clinical symptom scores (−2.21 vs. −0.31, P = 0.002) and a reduction in number of weekly SABA usage (−4.2 vs. 0.1, P < 0.01). In addition, patients in the inhaled therapy group achieved a significant improvement in HRQL based on mMRC (−1.51 vs. −0.31, P < 0.005) and SGRQ (−7.83 vs. −2.16, P < 0.01) scoring accompanied with no severe adverse events. There were fewer exacerbation frequencies in the combined inhaled therapy group over the 12 months of treatment compared to the control group (1 [0–2] vs. 2 [1–4], P = 0.017). Furthermore, stratified analysis indicated that combined inhaled therapy partially improve lung function for patients for whom it is severely impaired and those with pseudomonas aeruginosa isolated. Conclusion: Our results show that salmeterol-fluticasone combined inhaled therapy should be effective and safe for non-CF bronchiectasis patients

  3. Steroid secretion in polycystic ovarian disease after ovarian suppression by a long-acting gonadotropin-releasing hormone agonist.

    PubMed

    Chang, R J; Laufer, L R; Meldrum, D R; DeFazio, J; Lu, J K; Vale, W W; Rivier, J E; Judd, H L

    1983-05-01

    The principal glandular source of increased serum androgens in polycystic ovarian disease (PCO) is controversial), since complete separation of ovarian from adrenal function has not been achieved. The purpose of this study was to determine whether a long-acting GnRH agonist could be used to selectively inhibit ovarian steroid secretion in PCO and ovulatory women. Each of five typical PCO patients and six ovulatory subjects on day 2 of their menstrual cycles received D-Trp6-Pro9-NEt-LHRH (GnRH-a; 100 micrograms) for 28 consecutive days. Their results were compared to basal serum hormone values in eight oophorectomized women. In response to GnRH-a, PCO and normal subjects exhibited sharp and sustained rises of LH and gradual decreases in FSH. These levels were clearly less than basal levels seen in oophorectomized women. Episodic LH release was significantly attenuated in both groups at the end of GnRH-a treatment. After the administration of agonist, serum estradiol (E2), estrone (E1), androstenedione (A), and testosterone (T) were suppressed to castrate levels in both groups. The decrements of E2 and E1 in PCO were gradual and continuous compared to initial dramatic rises, which reached peaks at 14 days, and subsequent abrupt falls in the ovulatory controls. Serum A and T declined steadily in both groups. Basal serum dehydroepiandrosterone and dehydroepiandrosterone sulfate, but not cortisol, levels were elevated in PCO subjects. The 24-h secretion patterns and responses to ACTH of these hormones in PCO and ovulatory subjects were unaltered by GnRH-a administration. These data demonstrate that 1) in PCO subjects, GnRH-a induced complete suppression of ovarian steroid secretion, as circulating levels at the end of treatment were comparable to those seen in our oophorectomy subjects; 2) elevated A and T levels in PCO patients were derived primarily from the ovary; and 3) adrenal steroid secretion was unaltered by GnRH-a in both PCO and normal women.

  4. The Tupange Project in Kenya: A Multifaceted Approach to Increasing Use of Long-Acting Reversible Contraceptives

    PubMed Central

    Muthamia, Michael; Owino, Kenneth; Nyachae, Paul; Kilonzo, Margaret; Kamau, Mercy; Otai, Jane; Kabue, Mark; Keyonzo, Nelson

    2016-01-01

    ABSTRACT Background: Long-acting reversible contraceptives (LARCs) are safe and highly effective, and they have higher continuation rates than short-acting methods. Because only a small percentage of sexually active women in Kenya use LARCs, the Tupange project implemented a multifaceted approach to increase uptake of LARCs, particularly among the urban poor. The project included on-site mentoring, whole-site orientation, commodity security, quality improvement, and multiple demand-promotion and service-provision strategies, in the context of wide method choice. We report on activities in Nairobi between July 2011 and December 2014, the project implementation period. Methods: We used a household longitudinal survey of women of reproductive age to measure changes in the contraceptive prevalence rate (CPR) and other family planning-related variables. At baseline in July 2010, 2,676 women were interviewed; about 50% were successfully tracked and interviewed at endline in December 2014. A baseline service delivery point (SDP) survey of 112 health facilities and 303 service providers was conducted in July 2011, and an endline SDP survey was conducted in December 2014 to measure facility-based interventions. The SDP baseline survey was conducted after the household survey, as facilities were selected based on where clients said they obtained services. Results: The project led to significant increases in use of implants and intrauterine devices (IUDs). Uptake of implants increased by 6.5 percentage points, from 2.4% at baseline to 8.9% by endline, and uptake of IUDs increased by 2.1 percentage points, from 2.2% to 4.3%. By the endline survey, 37.7% of clients using pills and injectables at baseline had switched to LARCs. Contraceptive use among the poorest and poor wealth quintiles increased by 20.5 and 21.5 percentage points, respectively, from baseline to endline. Various myths and misconceptions reported about family planning methods declined significantly between

  5. Efficacy of 4 Years of Octreotide Long-Acting Release Therapy in Patients With Severe Polycystic Liver Disease

    PubMed Central

    Hogan, Marie C.; Masyuk, Tetyana; Bergstralh, Eric; Li, Bill; Kremers, Walter K.; Vaughan, Lisa E.; Ihrke, Angela; Severson, Amanda L.; Irazabal, Maria V.; Glockner, James; LaRusso, Nicholas F.; Torres, Vicente E.

    2016-01-01

    Objective To observe the effect on total liver volume (TLV) on and off therapy in selected symptomatic patients with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PLD) who received octreotide long-acting release (OctLAR) for up to 4 years. Patients and Methods Twenty-eight of 42 participants in a prospective 2-year clinical trial of OctLAR (40 mg monthly) consisting of double-blind, randomized (year 1) and open-label treatment (year 2) phases reenrolled in a 2-year open-label extension (OLE) study after being off OctLAR a mean of 8.3 months (original study: July 1, 2007, through June 30, 2013). Participants underwent magnetic resonance imaging at baseline, years 1 and 2, reenrollment, and study completion. Primary end point: change in TLV; secondary end points: changes in total kidney volume, glomerular filtration rate, quality of life (QoL), safety, vital signs, and laboratory parameters. Results Twenty-five participants (59.5%) completed the OLE. Off therapy, TLVs increased a mean ± SD of 3.4%±8.2% per year; after resuming therapy, TLVs decreased a mean ± SD of −4.7%±6.1% per year. Despite regrowth off treatment, overall reductions were observed, with a median (interquartile range) TLV of 4047 mL (3107–7402 mL) at baseline and 3477 (2653–7131 mL) at study completion (−13.2%; P<.001) and with improved health-related QoL. Total kidney volumes increased, and glomerular filtration rates declined from 58.2 mL/min to 54.5 mL/min (n=16) in patients with ADPKD on therapy from baseline to study completion. Conclusion Therapy with OctLAR over 4 years in selected patients with symptomatic PLD arrested PLD progression, alleviating symptoms and improving health-related QoL. Discontinuation led to organ regrowth. Trial Registration: clinicaltrials.gov Identifier: NCT00426153. PMID:26166166

  6. Treatment and control of bovine sarcoptic and psoroptic mange infestation with ivermectin long-acting injectable (IVOMEC(®) GOLD).

    PubMed

    Hamel, Dietmar; Joachim, Anja; Löwenstein, Michael; Pfister, Kurt; Silaghi, Cornelia; Visser, Martin; Winter, Renate; Yoon, Stephen; Cramer, Luiz; Rehbein, Steffen

    2015-02-01

    The efficacy of ivermectin long-acting injection (IVM LAI, IVOMEC® GOLD, Merial; 3.15 % ivermectin w/v) formulation was evaluated in cattle with induced Sarcoptes scabiei var. bovis or Psoroptes ovis infestations. A total of 64 cattle were included in this series of four studies, with 16 animals per study. Approximately, 8 weeks following initial induced mite infestation, cattle were allocated to treatment groups based on decreasing pre-treatment bodyweights. Treatments (saline (control) or IVM LAI (630 mcg ivermectin/kg bodyweight) at 1 mL/50 kg bodyweight) were administered by a single subcutaneous injection in front of the right shoulder on Day 0. Skin scrapings were collected prior to treatment and at approximately weekly intervals for 8 weeks thereafter to establish live mite counts. Character and extent of skin lesions were evaluated at each sampling. Animals were weighed before treatment and at the end of the studies. Mite counts of the IVM LAI-treated animals were significantly (p < 0.05) lower than those of the controls in all four studies at all occasions post-treatment. In the two Sarcoptes studies, IVM LAI-treated cattle were free of mites at 14 days after treatment and in the Psoroptes studies at 13 or 28 days post-treatment. All IVM LAI-treated cattle remained free of mites to the end of the studies while all control animals remained infested. Mange lesions of the IVM LAI-treated animals improved significantly (p < 0.05) compared to those of the controls from Day 21 (Sarcoptes studies) and from Days 28 or 34 (Psoroptes studies). In all studies, mean weight gain over the 8 week post-treatment period was significantly (p < 0.05) higher for the IVM LAI-treated animals than for the controls: Sarcoptes studies, 64.1 and 68.6 kg vs. 46.9 and 48.6 kg, respectively; Psoroptes studies, 43.0 and 43.4 kg vs. 20.8 and 34.9 kg, respectively. All animals accepted the treatment well, and no treatment-related health problems and adverse events were

  7. Long-acting anticoagulant rodenticide poisoning: an evidence-based consensus guideline for out-of-hospital management.

    PubMed

    Caravati, E Martin; Erdman, Andrew R; Scharman, Elizabeth J; Woolf, Alan D; Chyka, Peter A; Cobaugh, Daniel J; Wax, Paul M; Manoguerra, Anthony S; Christianson, Gwenn; Nelson, Lewis S; Olson, Kent R; Booze, Lisa L; Troutman, William G

    2007-01-01

    The objective of this guideline is to assist poison center personnel in the out-of-hospital triage and initial management of patients with suspected exposure to long-acting anticoagulant rodenticides (LAAR). An evidence-based expert consensus process was used to create this guideline. It is based on an assessment of current scientific and clinical information. The panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and health professionals providing care. The grade of recommendation is in parentheses. 1) Patients with exposure due to suspected self-harm, abuse, misuse, or potentially malicious administration should be referred to an emergency department immediately regardless of the doses reported (Grade D). 2) Patients with symptoms of LAAR poisoning (e.g., bleeding, bruising) should be referred immediately to an emergency department for evaluation regardless of the doses reported (Grade C). 3) Patients with chronic ingestion of LAAR should be referred immediately to an emergency department for evaluation of intent and potential coagulopathy (Grade B). 4) Patients taking anticoagulants therapeutically and who ingest any dose of a LAAR should have a baseline prothrombin time measured and then again at 48-72 hours after ingestion (Grade D). 5) Patients with unintentional ingestion of less than 1 mg of LAAR active ingredient can be safely observed at home without laboratory monitoring. This includes practically all unintentional ingestions in children less than 6 years of age (Grade C). 6) Pregnant patients with unintentional exposure to less than 1 mg of LAAR active ingredient should be evaluated by their obstetrician or primary care provider as an outpatient. Immediate referral to an ED or clinic is not required (Grade D). 7) Patients with unintentional ingestion of 1 mg or more of active ingredient and are asymptomatic should be evaluated for coagulopathy at 48-72 hours after exposure

  8. Muscle Cramps

    MedlinePlus

    Muscle cramps are sudden, involuntary contractions or spasms in one or more of your muscles. They often occur after exercise or at night, ... to several minutes. It is a very common muscle problem. Muscle cramps can be caused by nerves ...

  9. Muscle Disorders

    MedlinePlus

    Your muscles help you move and help your body work. Different types of muscles have different jobs. There are many problems that can affect muscles. Muscle disorders can cause weakness, pain or even ...

  10. Muscle atrophy

    MedlinePlus

    Muscle wasting; Wasting; Atrophy of the muscles ... There are two types of muscle atrophy: disuse and neurogenic. Disuse atrophy is caused by not using the muscles enough . This type of atrophy can often be ...

  11. Muscle biopsy

    MedlinePlus

    ... the removal of a small piece of muscle tissue for examination. ... dystrophy Myopathic changes (destruction of the muscle) Necrosis (tissue death) of muscle Necrotizing vasculitis Traumatic muscle damage Polymyositis Additional conditions ...

  12. Which treatment for low back pain? A factorial randomised controlled trial comparing intravenous analgesics with oral analgesics in the emergency department and a centrally acting muscle relaxant with placebo over three days [ISRCTN09719705].

    PubMed

    Havel, Christof; Sieder, Anna; Herkner, Harald; Domanovits, Hans; Schmied, Mascha; Segel, Rudolf; Koreny, Maria; Laggner, Anton N; Müllner, Marcus

    2001-01-01

    BACKGROUND: About two thirds of adults suffer from backpain at some time during their life. In the emergency room many patients with acute back pain are treated with intravenous non-steroidal analgesics. Whether this treatment is superior to oral administration of non-steroidal analgesics is unknown. Intravenous administration, however, requires considerable amounts of resources and accounts for high workload in busy clinics. In the further course centrally acting muscle relaxants are prescribed but the effectiveness remains unclear. The objective of this study is on the one hand to compare the effectiveness of intravenous with oral non-steroidal analgesics for acute treatment and on the other hand to compare the effectiveness of a centrally active muscle relaxant with placebo given for three days after presentation to the ED (emergency department). METHODS/DESIGN: This study is intended as a randomised controlled factorial trial mainly for two reasons: (1) the sequence of treatments resembles the actual proceedings in every-day clinical practice, which is important for the generalisability of the results and (2) this design allows to take interactions between the two sequential treatment strategies into account. There is a patient preference arm included because patients preference is an important issue providing valuable information: (1) it allows to assess the interaction between desired treatment and outcome, (2) results can be extrapolated to a wider group while (3) conserving the advantages of a fully randomised controlled trial. CONCLUSION: We hope to shed more light on the effectiveness of treatment modalities available for acute low back pain.

  13. Which treatment for low back pain? A factorial randomised controlled trial comparing intravenous analgesics with oral analgesics in the emergency department and a centrally acting muscle relaxant with placebo over three days [ISRCTN09719705

    PubMed Central

    Havel, Christof; Sieder, Anna; Herkner, Harald; Domanovits, Hans; Schmied, Mascha; Segel, Rudolf; Koreny, Maria; Laggner, Anton N; Müllner, Marcus

    2001-01-01

    Background About two thirds of adults suffer from backpain at some time during their life. In the emergency room many patients with acute back pain are treated with intravenous non-steroidal analgesics. Whether this treatment is superior to oral administration of non-steroidal analgesics is unknown. Intravenous administration, however, requires considerable amounts of resources and accounts for high workload in busy clinics. In the further course centrally acting muscle relaxants are prescribed but the effectiveness remains unclear. The objective of this study is on the one hand to compare the effectiveness of intravenous with oral non-steroidal analgesics for acute treatment and on the other hand to compare the effectiveness of a centrally active muscle relaxant with placebo given for three days after presentation to the ED (emergency department). Methods/Design This study is intended as a randomised controlled factorial trial mainly for two reasons: (1) the sequence of treatments resembles the actual proceedings in every-day clinical practice, which is important for the generalisability of the results and (2) this design allows to take interactions between the two sequential treatment strategies into account. There is a patient preference arm included because patients preference is an important issue providing valuable information: (1) it allows to assess the interaction between desired treatment and outcome, (2) results can be extrapolated to a wider group while (3) conserving the advantages of a fully randomised controlled trial. Conclusion We hope to shed more light on the effectiveness of treatment modalities available for acute low back pain. PMID:11716789

  14. Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis

    PubMed Central

    Ismaila, Afisi Segun; Huisman, Eline L; Punekar, Yogesh Suresh; Karabis, Andreas

    2015-01-01

    Background Randomized, controlled trials comparing long-acting muscarinic antagonist (LAMA) efficacy in COPD are limited. This network meta-analysis (NMA) assessed the relative efficacy of tiotropium 18 µg once-daily (OD) and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD). Methods A systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs. A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1), transitional dyspnea index focal score, St George’s Respiratory Questionnaire score, and rescue medication use. Results Twenty-four studies (n=21,311) compared LAMAs with placebo/each other. Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval) in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06–125.60]; 117.20 mL [104.50–129.90]; 114.10 mL [103.10–125.20]; 136.70 mL [104.20–169.20]); 24-week trough FEV1 (128.10 mL [84.10–172.00]; 135.80 mL [123.10–148.30]; 106.40 mL [95.45–117.30]; 115.00 mL [74.51–155.30]); 24-week St George’s Respiratory Questionnaire score (−4.60 [−6.76 to −2.54]; −3.14 [−3.83 to −2.45]; −2.43 [−2.92 to −1.93]; −4.69 [−7.05 to −2.31]); 24-week transitional dyspnea index score (1.00 [0.41–1.59]; 1.01 [0.79–1.22]; 0.82 [0.62–1.02]; 1.00 [0.49–1.51]); and 24-week rescue medication use (data not available; −0.41 puffs/day [−0.62 to −0.20]; −0.52 puffs/day [−0.74 to −0.30]; −0.30 puffs/day [−0.81 to 0.21]). For 12-week trough FEV1, differences in change from baseline (95% credible interval) were −12.8 mL (−39.39 to 13.93), aclidinium versus tiotropium; 3.08 mL (−7.58 to 13.69), glycopyrronium versus tiotropium; 22.58 mL (−11.58 to 56.97), umeclidinium versus tiotropium; 15.90 mL (−11.60 to 43

  15. A prospective, open-label study to evaluate symptomatic remission in schizophrenia with risperidone long-acting injectable in Korea.

    PubMed

    Lee, Nam Young; Kim, Se Hyun; Cho, Seong Jin; Chung, Young-Cho; Jung, In Kwa; Kim, Chang Yoon; Kim, Duk Ho; Lee, Dong Geun; Lee, Yo Han; Lim, Weon Jeong; Na, Young Suk; Shin, Sang Eun; Woo, Jong-Min; Yoon, Jin Sang; Yoon, Bo-Hyun; Ahn, Yong Min; Kim, Yong Sik

    2014-09-01

    This study was designed to investigate long-term clinical outcomes of risperidone long-acting injectable (RLAI) in patients with schizophrenia or schizoaffective disorder. An open-label, 48-week, prospective study of RLAI treatment was carried out at 63 centers in South Korea. Initial and maintenance dosage of RLAI were adjusted according to clinical judgment. Efficacy was measured by the remission rate, continuation rate, and changes in the clinical measurements such as eight items of the Positive and Negative Symptom Scale (PANSS), the Clinical Global Impression - Severity, and the Schizophrenia Quality of Life Scale. In terms of the safety, Simpson-Angus rating Scale, adverse events (AEs), and BMI were investigated. Of the 522 patients who were enrolled, 472 patients who had been assessed on the eight items of PANSS at baseline and at least once during RLAI treatment were included in the intention-to-treat (ITT) population. The per-protocol (PP) population included 184 patients (39.0%), who completed all assessments during 48 weeks of the follow-up period. Total scores of eight items of PANSS, Clinical Global Impression - Severity, and Schizophrenia Quality of Life Scale were reduced significantly from baseline to endpoint in both ITT and PP populations. The mean dose (SD) of RLAI was 33.2 (7.6) mg. In the PP population, the number of patients who scored 1-3 on eight items of PANSS were 47 (25.5%) at baseline and 144 (78.3%) at 48 weeks. According to the remission defining as scores 1-3 on eight items of PANSS sustaining of at least 6 months' duration by Andreasen, the numbers of patients who achieved remission were 45 (24.5%) at 24 weeks and 120 (65.2%) at 48 weeks. A significant decrease in the mean score of Simpson-Angus rating Scale and a significant increase in BMI over time in last observation carried forward were observed, and patients who fulfilled the remission criteria during the study showed more weight gain than those who did not. During the study

  16. A randomized, double-blind, double-dummy comparison of short- and long-acting dihydrocodeine in chronic non-malignant pain.

    PubMed

    Pedersen, Line; Borchgrevink, Petter Christian; Breivik, Harald Petter; Fredheim, Olav Magnus Søndenå

    2014-05-01

    Guidelines for opioid treatment of chronic non-malignant pain recommend long-acting over short-acting opioid formulations. The evidence for this recommendation is weak. This study is a randomized, double-blind, double-dummy, 8-week comparison of long-acting dihydrocodeine tablets (DHC-Continus) with short-acting dihydrocodeine tablets in 60 patients with chronic non-malignant pain who were referred to a multidisciplinary pain clinic. All patients used codeine-paracetamol tablets before the trial, and paracetamol was added in both groups during the trial. The primary outcome was stability in pain intensity, measured as the difference between the highest and least pain intensity reported on an 11-point numerical rating scale in a 7-day diary. The secondary outcomes were differences in quality of life, quality of sleep, depression, and episodes of breakthrough pain between the 2 formulations. Spontaneously reported adverse events were recorded. In all, 38 patients completed the trial, and 22 withdrew before the end. The reasons for withdrawal were adverse events, lack of efficacy, or both, and were similar between the groups. There were no significant differences in stability of pain intensity between groups. There were no significant differences between groups in quality of sleep, depression, health-related quality of life, or adverse events. Breakthrough pain was experienced in both groups during the trial. Long-acting dihydrocodeine was not observed to be superior for any of the outcomes in this trial. The results of this study do not support current guidelines recommending long-acting opioids.

  17. Pharmacological studies of N-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine hydrochloride (MDL-899), a new long-acting antihypertensive vasodilator.

    PubMed

    Baldoli, E; Bianchi, G; Corsico, N; Di Francesco, G F

    1985-01-01

    N-(2,5-Dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine hydrochloride (MDL-899) is a new long-acting antihypertensive vasodilator which reduces the blood pressure of conscious hypertensive rats and dogs to normal levels. The oral doses that reduce blood pressure by 50 mmHg are: 4.4 mg/kg in conscious spontaneously hypertensive rats (SHR), 18 mg/kg in conscious Milan hypertensive strain (MHS) and 1.7 mg/kg in conscious renal hypertensive dog (RHD). The i.v. doses are 1.26, 3.2 and 0.9 mg/kg. The reduction in blood pressure is slow (peak effect at 3 h) and long-lasting (more than 7 h) after p.o. or i.v. administration. Tolerance to MDL-899 is seen to develop in hypertensive dogs, whereas in hypertensive rats this phenomenon never occurs. The compound antagonizes the development of hypertension when given to SHR between days 25 and 88. The haemodynamic study in conscious normotensive rats (labelled microspheres) demonstrated that the fall in blood pressure is accompanied by increases in heart rate and cardiac output and a decrease in total peripheral resistance. The lack of alpha-blocking activity, in the rat caudal artery "in vitro"; beta 2-stimulating activity, in SHR pretreated with propranolol, and prostaglandin (PG) release activity, in SHR pretreated with indomethacin, excludes the possibility that the hypotension is due to one of these mechanisms. MDL-899 given orally to rats has no important depressant effects on the CNS at hypotensive or higher doses and induces no adrenergic system stimulation symptoms (midriasis, exophthalmus). In comparison with hydralazine, it is slower in onset and longer lasting, devoid of adrenergic system stimulation, less toxic and nonmutagenic. They are equipotent after p.o. treatment. PMID:2862874

  18. Skeletal muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are approximately 650-850 muscles in the human body these include skeletal (striated), smooth and cardiac muscle. The approximation is based on what some anatomists consider separate muscle or muscle systems. Muscles are classified based on their anatomy (striated vs. smooth) and if they are v...

  19. Muscle Deoxygenation Causes Muscle Fatigue

    NASA Technical Reports Server (NTRS)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D.

    1999-01-01

    Muscle fatigue is a common musculoskeletal disorder in the work place, and may be a harbinger for more disabling cumulative trauma disorders. Although the cause of fatigue is multifactorial, reduced blood flow and muscle oxygenation may be the primary factor in causing muscle fatigue during low intensity muscle exertion. Muscle fatigue is defined as a reduction in muscle force production, and also occurs among astronauts who are subjected to postural constraints while performing lengthy, repetitive tasks. The objectives of this research are to: 1) develop an objective tool to study the role of decreased muscle oxygenation on muscle force production, and 2) to evaluate muscle fatigue during prolonged glovebox work.

  20. Muscle disorder

    MedlinePlus

    Myopathic changes; Myopathy; Muscle problem ... Blood tests sometimes show abnormally high muscle enzymes. If a muscle disorder might also affect other family members, genetic testing may be done. When someone has symptoms and signs ...

  1. Risk of cardiovascular events after initiation of long-acting bronchodilators in patients with chronic obstructive lung disease: A population-based study

    PubMed Central

    Aljaafareh, Almotasembellah; Valle, Jose Ruben; Lin, Yu-Li; Kuo, Yong-Fang; Sharma, Gulshan

    2016-01-01

    Objectives: Long-acting bronchodilators are mainstay treatment for moderate to severe chronic obstructive pulmonary disease. A growing body of evidence indicates an increased risk of cardiovascular events upon initiation of these medications. We hypothesize that this risk is higher in patients with chronic obstructive pulmonary disease who had a preexisting cardiovascular disease regardless of receipt of any cardiovascular medication. Methods: A retrospective cohort of patients with a diagnosis of chronic obstructive pulmonary disease based on two outpatient visits or one inpatient visit for chronic obstructive pulmonary disease (International Classification of Diseases, 9th Edition, Clinical Modification codes 491.x, 492.x, 496) in any year between 2001 and 2012 from a commercial insurance database. We then selected those initiating long-acting bronchodilator treatments between April 2001 and September 2012. Each patient had a 1 year look back period to determine history of cardiovascular disease or cardiovascular disease treatment from the time of first prescription of long-acting beta agonist, long-acting muscarinic antagonist, or long-acting beta agonist combined with inhaled corticosteroids. Patients were followed for 90 days for hospitalizations or emergency department visits for cardiovascular event. The cohort was divided into four groups based on the presence of cardiovascular disease (including ischemic heart disease, hypertension, ischemic stroke, heart failure, tachyarrhythmias and artery disease based on International Classification of Diseases, 9th Edition, Clinical Modification codes) and cardiovascular disease treatment defined as acetylsalicylic acid, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antiplatelet, anticoagulants, calcium channel blockers, nitrate, digoxin, diuretics, antiarrhythmics or statins. Odds of emergency department visit or hospitalization in the 90 days after prescription were

  2. Demand for long acting and permanent methods of contraceptives and factors for non-use among married women of Goba Town, Bale Zone, South East Ethiopia

    PubMed Central

    2012-01-01

    Background Contraceptive use including short acting, long acting and permanent methods positively influence the socio-economic development of a nation by allowing families to space and limit their family size to their economic capacity. Demand for LAPMs of contraception as detrmined by utilization and unmet need for LAPMs of contraception can provide realiable information for providers. Objective To determine the utilization of long acting and permanent contraception and its associated factors among married women of Goba town, South East Ethiopia. Methods A cross sectional community based study was conducted among 734 systematically selected married women of reproductive age in Goba town in September/ 2009. A structured and pretested, interview questionaire was used to collect data on socio-demographic, behavioral factors and data related to demand for LAPMs of contraception. Data were analyzed using EPI INFO and SPSS version 16. Result The demand for Long Acting and Permanent Methods (LAPMs) of contraception was 18.1%. Utilization of LAPMs of contraception in the town was 64 (8.7%) and the unmet need for LAPMs was 69 (9.4%). Information on LAPMs in the town was 636 (86.6%). Media (radio and television) was the major sources of information 641 (87.3%). The use of LAPMs was significatly associated with ever use AOR[17.43, 95% CI:9.19, 33.03], number of times discussions made on methods AOR[4.6, 95% CI: 1.72,12.17] and main decider of using methods AOR[ 2.2, 95% CI:1.03, 4.65]. It was not associated with socio-demographic variables. Conclusion and recommendation The utilization of LAPMs in the town was less although higher than the Ethiopian demographic and health survey 2005 result. Moreover, there was a considerable unmet need. Increase the method mix of LAPMs by incorporating varaies of implnats in order to increase utilization. Proper counseling of client and partners discussion were some of the recommendation forwarded. PMID:23102166

  3. Reducing Prescriptions of Long-Acting Benzodiazepine Drugs in Denmark: A Descriptive Analysis of Nationwide Prescriptions during a 10-Year Period.

    PubMed

    Eriksen, Sophie Isabel; Bjerrum, Lars

    2015-06-01

    Prolonged consumption of benzodiazepine drugs (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone; altogether Z drugs) is related to potential physiological and psychological dependence along with other adverse effects. This study aimed to analyse the prescribing of long-acting BZD (half-life >10 hr), compared to short-acting BZD in Denmark during a 10-year period. Descriptive analysis of total sales data from the Danish Register of Medicinal Product Statistics, to individuals in the primary healthcare sector, of all BZD and Z drugs in the period of 2003-2013. Prescription data derive from all community and hospital pharmacies in Denmark. The prescribing of long-acting BZD was reduced from 25.8 defined daily doses (DDD)/1000 inhabitants/day in 2003 to 8.8 DDD/1000 inhabitants/day in 2013, a relative reduction of 66%. The prescribing of short-acting BZD was reduced from 26.1 DDD/1000 inhabitants/day in 2003 to 16.4 DDD/1000 inhabitants/day in 2013, a relative reduction of 37%. Prescription data in this study did not include information about indications for initiating treatments. In addition, due to compliance problems, some of the prescribed drugs may not have been consumed according to the prescription. The observed reduction in BZD use was correlated to the introduction of new national guidelines on prescription of addictive drugs, but this study was not designed to detect a causal relationship. The prescribing of long-acting BZD decreased considerably more than the prescribing of short-acting BZD in the 10-year period. PMID:25382355

  4. Maintenance treatment of chronic schizophrenic patients. A study with the long-acting thioxanthene derivative, cis(Z)-clopenthixol decanoate-sordinol depot.

    PubMed

    Dom, R; De Mesmaecker, L; van den Broucke, M; van Hest, T; Baro, F

    1978-04-01

    The clinical effect of clopenthixol decanoate has been assessed in a 5-month controlled including 21 hospitalized chronic schizophrenic patients. The ratings were done with BPRS, NOSIE 30, the two psychological tests of WAIS and Grübaum, and the rating scale of Simpson & Angus to assess extrapyramidal side effects. Clopenthixol decanoate was found an effective and long-acting antipsychotic compound with few autonomic and neurological side effects. Compared with previous maintenance treatment it also showed a positive influence on depression and facilitation of the social adaptation of the patients.

  5. Utilization, Spending, and Price Trends for Short- and Long-Acting Beta-Agonists and Inhaled Corticosteroids in the Medicaid Program, 1991–2010

    PubMed Central

    Chiu, Shih-Feng; Kelton, Christina M.L.; Guo, Jeff Jianfei; Wigle, Patricia R.; Lin, Alex C.; Szeinbach, Sheryl L.

    2011-01-01

    Background Asthma is a chronic respiratory disease that afflicts millions of people and accounts for substantial utilization of healthcare resources in most industrialized countries, including in the United States. However, the exact cost and utilization of anti-asthma medications in Medicaid in the past 2 decades have not been well studied. Considering the safety issues surrounding the long-acting beta-agonists, guideline updates, and the increase in asthma prevalence, understanding anti-asthma medication prescribing trends is important to payers and patients. Goal The purpose of this study was to analyze the utilization and spending trends for anti-asthmatic agents in the US Medicaid program over the past 2 decades. Methods This study was based on a retrospective, descriptive analysis of trends in utilization of and spending on anti-asthma medications, including short-acting beta-agonists, inhaled corticosteroids, long-acting beta-agonists, and inhaled corticosteroid/long-acting beta-agonist combinations. Quarterly utilization and expenditure data were obtained from the national Medicaid pharmacy files provided by the Centers for Medicare & Medicaid Services from quarter 1 of 1991 through quarter 2 of 2010. Average reimbursement per prescription was calculated each quarter as a proxy for drug price. Results The total number of prescriptions for the studied anti-asthma medications rose from 8.9 million in 1991 to 15.6 million in 2009, peaking at 20.8 million in 2005, the year before Medicare and Medicaid dual-eligible beneficiaries were moved to Medicare Part D. From 1991 to 2009, Medicaid spending on anti-asthma medications overall rose from $180.7 million to $1.3 billion, and spending on inhaled corticosteroid/long-acting beta-agonist combinations rose from $52.8 million in 2001—their first year on the market—to $411.7 million in 2009. The average price per prescription has risen in all the anti-asthma drug classes: overall, spending per prescription has

  6. Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis

    PubMed Central

    Tricco, Andrea C; Ashoor, Huda M; Antony, Jesmin; Beyene, Joseph; Veroniki, Areti Angeliki; Isaranuwatchai, Wanrudee; Harrington, Alana; Wilson, Charlotte; Tsouros, Sophia; Soobiah, Charlene; Yu, Catherine H; Hutton, Brian; Hoch, Jeffrey S; Hemmelgarn, Brenda R; Moher, David; Majumdar, Sumit R

    2014-01-01

    Objective To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes. Design Systematic review and network meta-analysis. Data sources Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013. Study selection Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included. Results 39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference −0.39%, 95% confidence interval −0.59% to −0.19%; −0.26%, −0.48% to −0.03%; and −0.36%, −0.65% to −0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: −5.51 kg, −6.56 to −4.46 kg; glargine once daily versus NPH once daily: −5.14 kg, −6.07 to −4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses

  7. A Long-Acting BMP-2 Release System Based on Poly(3-hydroxybutyrate) Nanoparticles Modified by Amphiphilic Phospholipid for Osteogenic Differentiation

    PubMed Central

    Peng, Xiaochun; Chen, Yunsu; Li, Yamin; Wang, Yiming

    2016-01-01

    We explored a novel poly(3-hydroxybutyrate) (PHB) nanoparticle loaded with hydrophilic recombinant human BMP-2 with amphiphilic phospholipid (BPC-PHB NP) for a rapid-acting and long-acting delivery system of BMP-2 for osteogenic differentiation. The BPC-PHB NPs were prepared by a solvent evaporation method and showed a spherical particle with a mean particle size of 253.4 nm, mean zeta potential of −22.42 mV, and high entrapment efficiency of 77.18%, respectively. For BPC-PHB NPs, a short initial burst release of BMP-2 from NPs in 24 h was found and it has steadily risen to reach about 80% in 20 days for in vitro test. BPC-PHB NPs significantly reduced the burst release of BMP-2, as compared to that of PHB NPs loading BMP-2 without PL (B-PHB NPs). BPC-PHB NPs maintained the content of BMP-2 for a long-term osteogenic differentiation. The OCT-1 cells with BPC-PHB NPs have high ALP activity in comparison with others. The gene markers for osteogenic differentiation were significantly upregulated for sample with BPC-PHB NPs, implying that BPC-PHB NPs can be used as a rapid-acting and long-acting BMP-2 delivery system for osteogenic differentiation. PMID:27379249

  8. Pituitary apoplexy causing spontaneous remission of acromegaly following long-acting octreotide therapy: a rare drug side effect or just a coincidence.

    PubMed

    Kumar, Sunil; Sharma, Shruti

    2016-04-01

    Pituitary apoplexy is characterized by abrupt onset of haemorrhage or non-haemorrhagic infarction of a pituitary adenoma. The clinical features include acute onset severe headache, visual field defects, meningeal irritation, ophthalmoplegia and hypopituitarism. The pituitary apoplexy may be clinically silent in ∼25% of patients. We report a case of acromegaly due to pituitary macroadenoma. The patient was started on long-acting octreotide therapy. On 3-month follow-up, the patient showed clinical and biochemical remission and the magnetic resonance imaging (MRI) of the brain showed subclinical haemorrhage and resolution of tumour. The octreotide therapy was stopped. On 6-month follow-up, the patient was still in remission and the MRI of brain revealed non-enhancing mixed intensities haemorrhagic and cystic areas of the pituitary gland. In our patient, whether spontaneous remission of acromegaly due to subclinical pituitary haemorrhage was coincidental or due to long-acting octreotide therapy is still a dilemma. We report this case because of rarity and clinical importance of this unusual occurrence. PMID:27123308

  9. Effects of a long-acting trace mineral rumen bolus supplement on growth performance, metabolic profiles, and trace mineral status of growing camels.

    PubMed

    Alhidary, Ibrahim A; Abdelrahman, Mutassim M; Harron, Raafat M

    2016-04-01

    A study was conducted to evaluate the effects of a long-acting trace mineral rumen bolus (TMB) supplement on the productive performance, metabolic profiles, and trace mineral status of growing camels under natural grazing conditions. Fifteen 6-month-old growing male camels (average bodyweight 139.51 ± 26.49 kg) were used in a 150-day trial. Animals were individually housed in a shaded pen and randomly assigned to receive zero (control group, CON), one (TMB1), or two (TMB2) long-acting TMBs. Feed intake was measured weekly, and camels were weighed monthly. Blood samples were collected from all camels on days 1, 30, 60, 90, 120, and 150 to obtain metabolic profiles. Zinc, selenium, copper, cobalt, and manganese concentrations were determined in the diet, serum, and liver. In comparison with controls, giving camels one TMB increased the average daily gain (14.38%; P < 0.04) and feed efficiency (13.68%; P < 0.01). Additionally, the serum and liver concentrations of zinc, copper, selenium, cobalt, and manganese were greater (P < 0.01) in camels in the TMB2 group. These data indicate that TMB supplementation has positive effects on the growth performance and trace mineral profiles of camels. Different levels, sources, and synergistic combinations of trace minerals can be used in further studies to elucidate their abilities to increase productive variables as well as their availability and cost to the camel industry. PMID:26894497

  10. Pituitary apoplexy causing spontaneous remission of acromegaly following long-acting octreotide therapy: a rare drug side effect or just a coincidence

    PubMed Central

    Kumar, Sunil; Sharma, Shruti

    2016-01-01

    Pituitary apoplexy is characterized by abrupt onset of haemorrhage or non-haemorrhagic infarction of a pituitary adenoma. The clinical features include acute onset severe headache, visual field defects, meningeal irritation, ophthalmoplegia and hypopituitarism. The pituitary apoplexy may be clinically silent in ∼25% of patients. We report a case of acromegaly due to pituitary macroadenoma. The patient was started on long-acting octreotide therapy. On 3-month follow-up, the patient showed clinical and biochemical remission and the magnetic resonance imaging (MRI) of the brain showed subclinical haemorrhage and resolution of tumour. The octreotide therapy was stopped. On 6-month follow-up, the patient was still in remission and the MRI of brain revealed non-enhancing mixed intensities haemorrhagic and cystic areas of the pituitary gland. In our patient, whether spontaneous remission of acromegaly due to subclinical pituitary haemorrhage was coincidental or due to long-acting octreotide therapy is still a dilemma. We report this case because of rarity and clinical importance of this unusual occurrence. PMID:27123308

  11. Oral Cysticercosis- A Diagnostic Dilemma

    PubMed Central

    Palakurthy, Pavan; Muddana, Keerthi; Nandan, Rateesh Kumar

    2015-01-01

    Cysticercosis, a helminthic disease commonly seen in India, Latin America, Eastern Europe and Southern Africa, results from extraintestinal encystation of the larval form of Taenia solium. It is a condition in which man acts as intermediate host instead of definitive host. The most frequent sites of cysticercosis are subcutaneous layers, brain, muscles, heart, liver, lungs, and peritoneum. Oral cysticercosis is considered rare and cause cystic swellings or nodules in the mouth and a precise clinical diagnosis is not usually established. Here, we report a case of oral cysticercosis in a 32-year-old female occurring in the mentalis muscle presenting as asymptomatic nodule. PMID:26266222

  12. An "enigmatic" L-carnosine (β-alanyl-L-histidine)? Cell proliferative activity as a fundamental property of a natural dipeptide inherent to traditional antioxidant, anti-aging biological activities: balancing and a hormonally correct agent, novel patented oral therapy dosage formulation for mobility, skeletal muscle power and functional performance, hypothalamic-pituitary- brain relationship in health, aging and stress studies.

    PubMed

    Babizhayev, Mark A; Yegorov, Yegor E

    2015-01-01

    Hypothalamic releasing and inhibiting hormones are major neuroendocrine regulators of human body metabolism being driven directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. The alternative physiological or therapeutic interventions utilizing the pharmaco-nutritional boost of imidazole-containing dipeptides (non-hydrolized oral form of carnosine, carcinine, N-acetylcarnosine lubricant eye drops) can maintain health, enhance physical exercise performance and prevent ageing. Carnosine (β-alanyl-L-histidine) is synthesized in mammalian skeletal muscle. There is an evidence that the release of carnosine from the skeletal muscle sarcomeres moieties during physical exercise affects autonomic neurotransmission and physiological functions. Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function. Carnosine and its imidazole-containing dipeptide derivatives are renowned for their anti-aging, antioxidant, membrane protective, metal ion chelating, buffering, anti-glycation/ transglycating activities used to prevent and treat a spectrum of age-related and metabolic diseases, such as neurodegenerative disease, sight threatening eye diseases, Diabetes mellitus and its complications, cancers and other disorders due to their wide spectrum biological activities. The precursor of carnosine (and related imidazole containing compounds) synthesis in skeletal muscles beta-alanine is used as the

  13. Short report: study on the efficacy of a new long-acting formulation of N, N-diethyl-m-toluamide (DEET) for the prevention of tick attachment.

    PubMed

    Salafsky, B; He, Y X; Li, J; Shibuya, T; Ramaswamy, K

    2000-02-01

    The beneficial effects of N, N-diethyl-m-toluamide (DEET) against biting insects of human and animals appear to last <6 hr after a single application to the skin. To prolong the repellent effects of DEET, recently we developed a new long-acting formulation of DEET called LIPODEET. This preparation was retained in the skin for a longer duration of time with minimal systemic absorption. In this study, we have evaluated the protective effect of three compounds (DEET, LIPODEET, and Morpel 220) against attachment of two species of ticks (Amblyomma americanum and Dermacentor variabilis) to rabbit ears. Results show that LIPODEET and Morpel 220 were highly effective in preventing tick attachment to the skin for a longer duration of time (up to 72 hr) than DEET after a single application. Moreover, LIPODEET was found to be acaricidal to both the species of ticks. PMID:10813468

  14. Fabrication of long-acting drug release property of hierarchical porous bioglasses/polylactic acid fibre scaffolds for bone tissue engineering.

    PubMed

    Wang, Dan; Lin, Huiming; Jiang, Jingjie; Jin, Qumei; Li, Lei; Dong, Yan; Qu, Fengyu

    2015-04-01

    Hierarchical porous fibre scaffolds with mesoporous bioglasses (MBGs) and polylactic acid (PLA) were successfully fabricated by the electrospinning method. These compound scaffolds possess macropores with sizes of about 100 nm because of the solvent evaporation from the fibre and the mesoporous structure ( ∼4.0 nm) originated from MBGs. The biomineralisation ability was investigated in simulated body fluid. The fibre structure is beneficial for inducing the growth of hydroxyapatite. In addition, compared with pure MBGs, the materials (MP-1 and MP-2) exhibit a long-acting drug release process up to 140 h and the drug release process corresponds with the Fickian diffusion mechanism. With the special fibre morphology and the hierarchical porous structure, the MBGs/PLA fibre scaffolds are expected to have potential application for bone tissue repair and regeneration.

  15. Degludec, a new ultra-long-acting basal insulin for the treatment of diabetes mellitus type 1 and 2: advances in clinical research.

    PubMed

    Muñoz Torres, Manuel

    2014-03-01

    Degludec is the most recent molecule of the ultra-long-acting basal insulin analogues approved for human use. It forms soluble multihexamers which after subcutaneous injection are converted into monomers, and are thus slowly and continuously absorbed into the bloodstream. This absorption mechanism confers degludec an ultra-long and stable action profile, with no concentration peaks. This paper discusses the most recent studies in patients with type 1 and 2 diabetes mellitus, which showed degludec to be non inferior in decreasing HbA1c, ensuring optimum glycemic control similar to that achieved with insulin glargine or detemir. Degludec also had an improved safety profile, as it was associated to a significantly lower rate of nocturnal hypoglycemia in both types of diabetes and to a potentially lower overall hypoglycemia rate in type 2 DM. Degludec also opens the possibility to use more flexible regimens.

  16. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology. PMID:16277953

  17. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology.

  18. Effects of roflumilast in COPD patients receiving inhaled corticosteroid/long-acting β2-agonist fixed-dose combination: RE2SPOND rationale and study design

    PubMed Central

    Rennard, Stephen I; Martinez, Fernando J; Rabe, Klaus F; Sethi, Sanjay; Pizzichini, Emilio; McIvor, Andrew; Siddiqui, Shahid; Anzueto, Antonio; Zhu, Haiyuan

    2016-01-01

    Background Roflumilast, a once-daily, selective phosphodiesterase-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The RE2SPOND study is examining whether roflumilast, when added to an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fixed-dose combination (FDC), further reduces exacerbations. The methodology is described herein. Methods In this Phase IV, multicenter, double-blind, placebo-controlled, parallel-group trial, participants were randomized 1:1 (stratified by long-acting muscarinic antagonist use) to receive roflumilast or placebo, plus ICS/LABA FDC, for 52 weeks. Eligible participants had severe COPD associated with chronic bronchitis, had two or more moderate–severe exacerbations within 12 months, and were receiving ICS/LABA FDC for ≥3 months. The primary efficacy measure is the rate of moderate or severe COPD exacerbations per participant per year. The secondary efficacy outcomes include mean change in prebronchodilator forced expiratory volume in 1 second (FEV1) over 52 weeks, rate of severe exacerbations, and rate of moderate, severe, or antibiotic-treated exacerbations. Additional assessments include spirometry, rescue medication use, the COPD assessment test, daily symptoms using the EXACT-Respiratory symptoms (E-RS) questionnaire, all-cause and COPD-related hospitalizations, and safety and pharmacokinetic measures. Results Across 17 countries, 2,354 participants were randomized from September 2011 to October 2014. Enrollment goal was met in October 2014, and study completion occurred in June 2016. Conclusion This study will further characterize the effects of roflumilast added to ICS/LABA on exacerbation rates, lung function, and health of severe–very severe COPD participants at risk of further exacerbations. The results will determine the clinical benefits of roflumilast combined with standard-of-care inhaled COPD treatment. PMID

  19. The reassertion profiles of long acting β2-adrenoceptor agonists in the guinea pig isolated trachea and human recombinant β2-adrenoceptor.

    PubMed

    Patel, S; Summerhill, S; Stanley, M; Perros-Huguet, C; Trevethick, M A

    2011-04-01

    Long acting β(2)-adrenoceptor agonists as exemplified by salmeterol and formoterol, exhibit reassertion behaviour in isolated airway preparations. This phenomenon is the inhibition of relaxation by a β(2)-antagonist (e.g. sotalol), followed by the re-establishment of the relaxation when all drugs have been washed out and in the absence of any further agonist addition to the bathing solution. In this study we have compared the reassertion behaviour of salmeterol and formoterol with the new long acting β(2)-adrenoceptor agonists indacaterol, carmoterol and three Pfizer agonists (PF610,355, PF613,322, UK503590) in the guinea pig isolated trachea and in a novel assay developed in CHO cells expressing the recombinant human β(2)-adrenoceptor. The results obtained can be divided into two groups: salmeterol-like (persistent duration of action following agonist removal--coupled with reassertion behaviour), as exemplified by indacaterol, PF610,355, PF613,322 and UK503,590 and, formoterol-like (short duration of agonist action and little reassertion behaviour unless supramaximal concentrations are used), as exemplified by carmoterol. Results are discussed in the context of the two theories proposed to explain the long duration of action of salmeterol (binding to a specific 'exosite' of the β(2)-adrenoceptor) and formoterol (membrane deposition: micro-kinetic theory). Our data suggest that the micro-kinetic theory is an adequate explanation to explain the long duration of action of the β(2)-adrenoceptor agonists studied in these two assays, although with the current data set we cannot definitively exclude the 'exosite' theory. PMID:21134482

  20. Long-acting neuroleptic use for reproductive management of non-domestic ungulates using the domestic goat (Capra hircus) as a model.

    PubMed

    Weiss, Rachael B; Schook, Mandi W; Wolfe, Barbara A

    2014-01-01

    Fluphenazine decanoate is a long-acting phenothiazine neuroleptic that attenuates the stress response and may be useful during intensive handling for reproductive procedures in non-domestic ungulates. However, phenothiazines are also associated with elevated serum prolactin, which can suppress fertility in some species. For this study, 10 female domestic goats were used as a model for non-domestic caprids to test effects of fluphenazine decanoate on serum cortisol and reproductive cyclicity following estrus synchronization. Two identical trials were conducted during the breeding season, employing a random crossover design. First, females underwent estrus synchronization using a 14-day treatment with progesterone (330 mg; CIDR). After 7 days of CIDR exposure, the treatment group (n = 5) received fluphenazine decanoate (1.0 mg/kg IM) and controls (n = 5) received an equivalent volume of 0.9% saline IM. At CIDR withdrawal (Day 14), animals received 125 mg cloprostenol sodium to lyse any luteal tissue and synchronize estrus. Blood was collected every 2 hr from 36 hr after CIDR withdrawal until 24 hr after standing estrus, or up to 5 days to monitor stress and reproductive hormones. Serum cortisol, prolactin, luteinizing hormone (LH) and progesterone concentrations were determined by enzyme immunoassay. While treatment with fluphenazine was associated with lower cortisol concentrations compared to controls (P = 0.001), 4 of the 10 treated animals experienced elevated serum prolactin, suppression of the LH surge and inhibition of ovulation. These findings suggest that long-acting neuroleptic drugs reduce the adrenal stress response, but may interfere with reproductive responses and negatively influence breeding success. PMID:24644127

  1. Increasing Uptake of Long-Acting Reversible Contraceptives in Cambodia Through a Voucher Program: Evidence From a Difference-in-Differences Analysis

    PubMed Central

    Bajracharya, Ashish; Veasnakiry, Lo; Rathavy, Tung; Bellows, Ben

    2016-01-01

    ABSTRACT Objective: This article evaluates the use of modern contraceptives among poor women exposed to a family planning voucher program in Cambodia, with a particular focus on the uptake of long-acting reversible contraceptives (LARCs). Methods: We used a quasi-experimental study design and data from before-and-after intervention cross-sectional household surveys (conducted in 2011 and 2013) in 9 voucher program districts in Kampong Thom, Kampot, and Prey Veng provinces, as well as 9 comparison districts in neighboring provinces, to evaluate changes in use of modern contraceptives and particularly LARCs in the 12 months preceding each survey. Survey participants in the analytical sample were currently married, non-pregnant women ages 18 to 45 years (N = 1,936 at baseline; N = 1,986 at endline). Difference-in-differences (DID) analyses were used to examine the impact of the family planning voucher. Results: Modern contraceptive use increased in both intervention and control areas between baseline and endline: in intervention areas, from 22.4% to 31.6%, and in control areas, from 25.2% to 31.0%. LARC use also increased significantly between baseline and endline in both intervention (from 1.4% to 6.7%) and control (from 1.9% to 3.5%) areas, but the increase in LARC use was 3.7 percentage points greater in the intervention area than in the control area (P = .002), suggesting a positive and significant association of the voucher program with LARC use. The greatest increases occurred among the poorest and least educated women. Conclusion: A family planning voucher program can increase access to and use of more effective long-acting methods among the poor by reducing financial and information barriers. PMID:27540118

  2. Baclofen Oral

    MedlinePlus

    ... nerves and decreases the number and severity of muscle spasms caused by multiple sclerosis or spinal cord diseases. It also relieves pain and improves muscle movement.This medication is sometimes prescribed for other ...

  3. Zidovudine Oral

    MedlinePlus

    ... cell in the blood and cause anemia and muscle disorders. When used alone or in combination with other ... swelling of the muscle, anemia, a history of alcohol abuse, or bleeding or other blood problems.tell ...

  4. Modeling Muscles

    ERIC Educational Resources Information Center

    Goodwyn, Lauren; Salm, Sarah

    2007-01-01

    Teaching the anatomy of the muscle system to high school students can be challenging. Students often learn about muscle anatomy by memorizing information from textbooks or by observing plastic, inflexible models. Although these mediums help students learn about muscle placement, the mediums do not facilitate understanding regarding integration of…

  5. Oral cancer

    MedlinePlus

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... Oral cancer most commonly involves the lips or the tongue. It may also occur on the: Cheek lining Floor ...

  6. Nanoformulation strategies for the enhanced oral bioavailability of antiretroviral therapeutics.

    PubMed

    Tatham, Lee M; Rannard, Steven P; Owen, Andrew

    2015-01-01

    The oral delivery of drugs with poor aqueous solubility is challenging and often results in poor bioavailability. Various nanoformulation platforms have demonstrated improved oral bioavailability of a range of drugs for different indications. The focus of this review is to provide an overview of the application of nanomedicine to oral antiretroviral therapy and outline how the current short-falls of this life-long therapy may be resolved using nanotechnology. As well as highlighting the rationale for a nanomedicine-based approach, the review focuses on the various strategies used to enhance oral bioavailability and describes the mechanisms of particle absorption across the GI tract. The recent advances in the development of long-acting formulations for both HIV treatment and pre-exposure prophylaxis are also discussed.

  7. The effect of umeclidinium added to inhaled corticosteroid/long-acting β2-agonist in patients with symptomatic COPD: a randomised, double-blind, parallel-group study.

    PubMed

    Sousa, Ana R; Riley, John H; Church, Alison; Zhu, Chang-Qing; Punekar, Yogesh S; Fahy, William A

    2016-01-01

    Benefits of triple therapy with a long-acting muscarinic antagonist (LAMA), added to inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), have been demonstrated. Limited data assessing the efficacy of the LAMA umeclidinium (UMEC) added to ICS/LABA are available. The aim of this study is to evaluate the efficacy and safety of UMEC added to ICS/LABAs in patients with moderate-to-very-severe COPD. This is a multicentre, randomised, double-blind, parallel-group study. Patients were symptomatic (modified Medical Research Council Dyspnoea Scale score ⩾2), despite receiving ICS/LABA (fluticasone propionate/salmeterol (FP/SAL, branded) 500/50 mcg, budesonide/formoterol (BD/FOR, branded) 200/6 mcg or 400/12 mcg, or other ICS/LABAs) ⩾30 days before the run-in (7±2 days). Patients were randomised 1:1 to once-daily UMEC 62.5 mcg or placebo (PBO), added to twice-daily open-label ICS/LABA for 12 weeks. Primary end point was trough forced expiratory volume in 1 s (FEV1) at Day 85; secondary end point was weighted mean (WM) 0-6 h FEV1 at Day 84; other end points included COPD Assessment Test (CAT) score and Transition Dyspnoea Index (TDI) score. Adverse events (AEs) were investigated. In the UMEC+ICS/LABA and PBO+ICS/LABA groups, 119 and 117 patients were randomised, respectively. Patients received FP/SAL (40%), BD/FOR (43%) and other ICS/LABAs (17%). UMEC+ICS/LABA resulted in significant improvements in trough FEV1 (Day 85) and in WM 0-6 h FEV1 (Day 84) versus PBO+ICS/LABA (difference: 123 and 148 ml, respectively, both P<0.001). Change from baseline for UMEC+ICS/LABA versus PBO+ICS/LABA was significantly different for CAT score at Day 84 (-1.31, P<0.05), but not for TDI score (0.40, P=0.152). AE incidence was similar with UMEC+ICS/LABA (38%) and PBO+ICS/LABA (42%). UMEC+ICS/LABA improved lung function and CAT score in patients with symptomatic COPD versus PBO+ICS/LABA (ClinicalTrials.gov NCT02257372). PMID:27334739

  8. Two short-acting kappa opioid receptor antagonists (zyklophin and LY2444296) exhibited different behavioral effects from the long-acting antagonist norbinaltorphimine in mouse anxiety tests.

    PubMed

    Huang, Peng; Yakovleva, Tatyana; Aldrich, Jane V; Tunis, Julia; Parry, Christopher; Liu-Chen, Lee-Yuan

    2016-02-26

    Prototypical long-acting kappa opioid receptor (KOPR) antagonists [e.g., norbinaltorphimine (norBNI)] have been reported to exert anxiolytic-like effects in several commonly used anxiety tests in rodents including the novelty-induced hypophagia (NIH) and elevated plus maze (EPM) tests. It remains unknown if the short-acting KOPR antagonists (e.g., zyklophin and LY2444296) have similar effects. In this study effects of zyklophin and LY2444296 (s.c.) were investigated in the NIH and EPM tests in mice 1h post-injection and compared with norBNI (i.p.) 48h post-administration. In the NIH test, zyklophin at 3 and 1mg/kg, but not 0.3mg/kg, or LY2444296 at 30mg/kg decreased the latency of palatable food consumption in novel cages, but had no effect in training cages, similar to norBNI (10mg/kg). Zyklophin at 3 or 1mg/kg increased or had a trend of increasing the amount of palatable food consumption in novel cages, with no effects in training cages, further indicating its anxiolytic-like effect, but norBNI (10mg/kg) and LY2444296 (30mg/kg) did not. In the EPM test, norBNI (10mg/kg) increased open arm time and % open arm entries or time, but zyklophin at all three doses and LY2444296 (30mg/kg) had no effects. In addition, zyklophin at 3mg/kg increased numbers of close and total arm entries on EPM, suggesting increased activity; however, norBNI and LY2444296 had no effects on close and total arm entries. Thus, all three KOPR antagonists had anxiolytic-like effects in the NIH test. However, only the long-acting one (norBNI), but not the short-acting ones (zyklophin and LY2444296), demonstrated anti-anxiety like effects in the EPM test. It remains to be investigated if the differences are due to the differences in their durations of action and/or pharmacodynamic properties.

  9. A New Level A Type IVIVC for the Rational Design of Clinical Trials Toward Regulatory Approval of Generic Polymeric Long-Acting Injectables.

    PubMed

    Somayaji, Mahadevabharath R; Das, Debarun; Przekwas, Andrzej

    2016-10-01

    Chronic neuropsychiatric disorders and diabetes mellitus affect millions of patients and require long-term supervision and expensive medical care. Although repeated drug administration can help manage these diseases, relapses and re-hospitalization owing to patient non-adherence and reduced therapeutic efficacy remain challenging. In response, long-acting injectables, which provide sustained drug release over longer periods at concentrations close to therapeutic ranges, have been proposed. Recent advancements include polymeric long-acting injectables (pLAIs), in which the active pharmaceutical ingredient (API) is encapsulated within U.S. Food and Drug Administration (FDA)-approved biocompatible polymers, such as poly(lactic-co-glycolic acid), or PLGA. Despite significant progress and development in the global pLAI market, FDA guidance for the approval of complex drug products, such as generic pLAIs, is not clearly defined. Although in vitro to in vivo correlation (IVIVC) can facilitate the identification of critical quality attributes (CQAs), drug formulations, and in vitro test platforms for evaluating drug performance in vivo, the application of IVIVC in order to shortlist time- and resource-intensive clinical trials for generic pLAIs has not been reported. Here, we propose a new Level A Type IVIVC that directly correlates the in vitro outcomes, such as drug dissolution, of candidate generic formulations with the clinical characteristics, such as drug absorption, of a reference listed drug (RLD), to help identify the specific generic pLAI formulations with clinical absorptions that are likely to be similar to that of the RLD, thereby reducing the number of clinical trials required for evaluation of clinical bioequivalence (BE). Therefore, the scope of the proposed method is intended only for the rational design of clinical trials, i.e., to shortlist the specific pLAI generic formulations for clinical BE evaluation, and not necessarily to analyze drug performances

  10. A New Level A Type IVIVC for the Rational Design of Clinical Trials Toward Regulatory Approval of Generic Polymeric Long-Acting Injectables.

    PubMed

    Somayaji, Mahadevabharath R; Das, Debarun; Przekwas, Andrzej

    2016-10-01

    Chronic neuropsychiatric disorders and diabetes mellitus affect millions of patients and require long-term supervision and expensive medical care. Although repeated drug administration can help manage these diseases, relapses and re-hospitalization owing to patient non-adherence and reduced therapeutic efficacy remain challenging. In response, long-acting injectables, which provide sustained drug release over longer periods at concentrations close to therapeutic ranges, have been proposed. Recent advancements include polymeric long-acting injectables (pLAIs), in which the active pharmaceutical ingredient (API) is encapsulated within U.S. Food and Drug Administration (FDA)-approved biocompatible polymers, such as poly(lactic-co-glycolic acid), or PLGA. Despite significant progress and development in the global pLAI market, FDA guidance for the approval of complex drug products, such as generic pLAIs, is not clearly defined. Although in vitro to in vivo correlation (IVIVC) can facilitate the identification of critical quality attributes (CQAs), drug formulations, and in vitro test platforms for evaluating drug performance in vivo, the application of IVIVC in order to shortlist time- and resource-intensive clinical trials for generic pLAIs has not been reported. Here, we propose a new Level A Type IVIVC that directly correlates the in vitro outcomes, such as drug dissolution, of candidate generic formulations with the clinical characteristics, such as drug absorption, of a reference listed drug (RLD), to help identify the specific generic pLAI formulations with clinical absorptions that are likely to be similar to that of the RLD, thereby reducing the number of clinical trials required for evaluation of clinical bioequivalence (BE). Therefore, the scope of the proposed method is intended only for the rational design of clinical trials, i.e., to shortlist the specific pLAI generic formulations for clinical BE evaluation, and not necessarily to analyze drug performances

  11. Combination of long-acting microcapsules of the D-tryptophan-6 analog of luteinizing hormone-releasing hormone with chemotherapy: investigation in the rat prostate cancer model.

    PubMed Central

    Schally, A V; Redding, T W

    1985-01-01

    The effect of combining hormonal treatment consisting of long-acting microcapsules of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) with the chemotherapeutic agent cyclophosphamide was investigated in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Cyclophosphamide (Cytoxan) (5 mg/kg of body weight) was injected intraperitoneally twice a week. When the therapy was started 90 days after tumor transplantation--at the time that the cancers were well developed-and was continued for 2 months, tumor volume was significantly reduced by the microcapsules or Cytoxan given alone. The combination of these two agents similarly inhibited tumor growth but did not show a synergistic effect. In another study, the treatment was started 2 months after transplantation, when the developing tumors measured 60-70 mm3. Throughout the treatment period of 100 days, the microcapsules of [D-Trp6]LH-RH reduced tumor volume more than Cytoxan did, and the combination of the two drugs appeared to completely arrest tumor growth. Tumor weights also were diminished significantly in all experimental groups, the decrease in weight being smaller in the Cytoxan-treated group than in rats that received the microcapsules. The combination of Cytoxan plus the microcapsules was 10-100 times more effective than the single agents in reducing tumor weights. In both experiments, testes and ventral prostate weights were significantly diminished, serum testosterone was suppressed to undetectable levels, and prolactin values were reduced by administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Cytoxan. These results in rats suggest that combined administration of long acting microcapsules of [D-Trp6]LH-RH with a chemotherapeutic agent, started soon after the

  12. Comparative safety and effectiveness of long-acting inhaled agents for treating chronic obstructive pulmonary disease: a systematic review and network meta-analysis

    PubMed Central

    Tricco, Andrea C; Strifler, Lisa; Veroniki, Areti-Angeliki; Yazdi, Fatemeh; Khan, Paul A; Scott, Alistair; Ng, Carmen; Antony, Jesmin; Mrklas, Kelly; D'Souza, Jennifer; Cardoso, Roberta; Straus, Sharon E

    2015-01-01

    Objective To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD). Setting Systematic review and network meta-analysis (NMA). Participants 208 randomised clinical trials (RCTs) including 134 692 adults with COPD. Interventions LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo. Primary and secondary outcomes The proportion of patients with moderate-to-severe exacerbations. The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes. Results NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26 141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol. Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve). NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%). NMA was conducted on CVM (37 RCTs, 55 156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR). Triamcinolone acetonide was the most harmful (SUCRA=81%). NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone

  13. Assessment of pharmacokinetic compatibility of short acting CDRI candidate trioxane derivative, 99–411, with long acting prescription antimalarials, lumefantrine and piperaquine

    PubMed Central

    Taneja, Isha; Raju, Kanumuri Siva Rama; Singh, Sheelendra Pratap; Wahajuddin, Muhammad

    2015-01-01

    The pharmacokinetic compatibility of short-acting CDRI candidate antimalarial trioxane derivative, 99–411, was tested with long-acting prescription antimalarials, lumefantrine and piperaquine. LC-ESI-MS/MS methods were validated for simultaneous bioanalysis of lumefantrine and 99–411 and of piperaquine and 99–411 combinations. The interaction studies were performed in rats using these validated methods. The total systemic exposure of 99–411 increased when administered with either lumefantrine or piperaquine. However, co-administration of 99–411 significantly decreased the systemic exposure of piperaquine by half-fold while it had no effect on the kinetics of lumefantrine. 99–411, thus, seemed to be a good alternative to artemisinin derivatives for combination treatment with lumefantrine. To explore the reason for increased plasma levels of 99–411, an in situ permeability study was performed by co-perfusing lumefantrine and 99–411. In presence of lumefantrine, the absorption of 99–411 was significantly increased by 1.37 times than when given alone. Lumefantrine did not affect the metabolism of 99–411 when tested in vitro in human liver microsomes. Additionally, ATPase assay suggest that 99–411 was a substrate of human P-gp, thus, indicating the probability of interaction at the absorption level in humans as well. PMID:26602250

  14. Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase

    PubMed Central

    Melody, Kevin; McBeth, Sarah; Kline, Christopher; Kashuba, Angela D. M.; Mellors, John W.

    2015-01-01

    Preexposure prophylaxis (PrEP) using antiretroviral drugs is effective in reducing the risk of human immunodeficiency virus type 1 (HIV-1) infection, but adherence to the PrEP regimen is needed. To improve adherence, a long-acting injectable formulation of the nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV LA) has been developed. However, there are concerns that PrEP may select for drug-resistant mutations during preexisting or breakthrough infections, which could promote the spread of drug resistance and limit options for antiretroviral therapy. To address this concern, we administered RPV LA to macaques infected with simian immunodeficiency virus containing HIV-1 RT (RT-SHIV). Peak plasma RPV levels were equivalent to those reported in human trials and waned over time after dosing. RPV LA resulted in a 2-log decrease in plasma viremia, and the therapeutic effect was maintained for 15 weeks, until plasma drug concentrations dropped below 25 ng/ml. RT mutations E138G and E138Q were detected in single clones from plasma virus in separate animals only at one time point, and no resistance mutations were detected in viral RNA isolated from tissues. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities in vitro, whereas E138G conferred 2-fold resistance to RPV. Overall, selection of RPV-resistant variants was rare in an RT-SHIV macaque model despite prolonged exposure to slowly decreasing RPV concentrations following injection of RPV LA. PMID:26438501

  15. Is Household Wealth Associated With Use of Long-Acting Reversible and Permanent Methods of Contraception? A Multi-Country Analysis

    PubMed Central

    Ugaz, Jorge I; Chatterji, Minki; Gribble, James N; Banke, Kathryn

    2016-01-01

    Abstract As programs continue to expand access to family planning information, services, and products, it is critical that these efforts be undertaken with an equity lens, ensuring that regardless of socioeconomic status, all women and couples can use the method that meets their needs. This study explores the relationship between household wealth and the use of long-acting and permanent methods (LAPMs) versus short-acting methods of contraception among modern method users, using multivariate analyses based on Demographic Health Survey data from 30 developing countries conducted between 2006 and 2013. Overall, and controlling for relevant individual and household characteristics including age, number of living children, education, and urban/rural residence, we found that wealthier women were more likely than poorer women to use LAPMs instead of short-acting methods: 20 of the 30 countries showed a positive and statistically significant association between wealth and LAPM use. For 10 of those countries, however, LAPM use was significantly higher only for the top (1 or 2) wealthiest quintiles. Eight countries showed no broad pattern of association, while in 2 countries—Bangladesh and India—poorer women were more likely to use LAPMs than wealthier women. The positive association between wealth and LAPM use was found most consistently in the Latin American and the Caribbean countries in our sample. These findings can help program implementers respond better to women’s needs for modern contraception, especially in reaching women from lower- and middle-income households. PMID:27016543

  16. Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury

    PubMed Central

    Nishida, Kento; Watanabe, Hiroshi; Ogaki, Shigeru; Kodama, Azusa; Tanaka, Ryota; Imafuku, Tadashi; Ishima, Yu; Giam Chuang, Victor Tuan; Toyoda, Masao; Kondoh, Masumi; Wu, Qiong; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

    2015-01-01

    Rhabdomyolysis-associated acute kidney injury (AKI) is a serious life-threatening condition. As such, more effective strategies are needed for its prevention. Thioredoxin-1 (Trx), a redox-active and macrophage migration inhibitory factor (MIF) modulating protein, has a short retention time in the blood. We examined the renoprotective effect of long acting Trx that was genetically fused with human serum albumin (HSA-Trx) against glycerol-induced AKI. An intravenous HSA-Trx pre-treatment attenuated the glycerol-induced decline in renal function, compared to a PBS, HSA or Trx alone. HSA-Trx caused a reduction in the tubular injuries and in the number of apoptosis-positive tubular cells. Renal superoxide, 8-hydroxy deoxyguanosine, nitrotyrosine and the plasma Cys34-cysteinylated albumin were clearly suppressed by the HSA-Trx treatment. Prior to decreasing TNF-α and IL-6, HSA-Trx suppressed an increase of plasma MIF level. In LLC-PK1 cells, HSA-Trx decreased the level of reactive oxygen species and lactate dehydrogenase release induced by myoglobin. HSA-Trx treatment resulted in a threefold increase in the survival of lethal glycerol-treated mice. The post-administration of HSA-Trx at 1 and 3 hr after glycerol injection exerted a significant renoprotective effect. These results suggest HSA-Trx has potential for use in the treatment of rhabdomyolysis-associated AKI via its extended effects of modulating oxidative stress and MIF. PMID:26412311

  17. PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates.

    PubMed

    Thompson, W Clayton; Zhou, Yingjiang; Talukdar, Saswata; Musante, Cynthia J

    2016-08-01

    PF-05231023, a long-acting FGF21 analogue, is a promising potential pharmacotherapy for the treatment of obesity and associated comorbidities. Previous studies have shown the potential of FGF21 and FGF21-like compounds to decrease body weight in mice, non-human primates, and humans; the precise mechanisms of action remain unclear. In particular, there have been conflicting reports on the degree to which FGF21-induced weight loss in non-human primates is attributable to a decrease in food intake versus an increase in energy expenditure. Here, we present a semi-mechanistic mathematical model of energy balance and body composition developed from similar work in mice. This model links PF-05231023 administration and washout to changes in food intake, which in turn drives changes in body weight. The model is calibrated to and compared with recently published data from cynomolgus macaques treated with PF-05231023, demonstrating its accuracy in describing pharmacotherapy-induced weight loss in these animals. The results are consistent with the hypothesis that PF-05231023 decreases body weight in cynomolgus macaques solely by a reduction in food intake, with no direct effect on energy expenditure. PMID:27405817

  18. A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects.

    PubMed

    Talukdar, Saswata; Zhou, Yingjiang; Li, Dongmei; Rossulek, Michelle; Dong, Jennifer; Somayaji, Veena; Weng, Yan; Clark, Ronald; Lanba, Adhiraj; Owen, Bryn M; Brenner, Martin B; Trimmer, Jeffrey K; Gropp, Kathryn E; Chabot, Jeffrey R; Erion, Derek M; Rolph, Timothy P; Goodwin, Bryan; Calle, Roberto A

    2016-03-01

    FGF21 plays a central role in energy, lipid, and glucose homeostasis. To characterize the pharmacologic effects of FGF21, we administered a long-acting FGF21 analog, PF-05231023, to obese cynomolgus monkeys. PF-05231023 caused a marked decrease in food intake that led to reduced body weight. To assess the effects of PF-05231023 in humans, we conducted a placebo-controlled, multiple ascending-dose study in overweight/obese subjects with type 2 diabetes. PF-05231023 treatment resulted in a significant decrease in body weight, improved plasma lipoprotein profile, and increased adiponectin levels. Importantly, there were no significant effects of PF-05231023 on glycemic control. PF-05231023 treatment led to dose-dependent changes in multiple markers of bone formation and resorption and elevated insulin-like growth factor 1. The favorable effects of PF-05231023 on body weight support further evaluation of this molecule for the treatment of obesity. Longer studies are needed to assess potential direct effects of FGF21 on bone in humans. PMID:26959184

  19. Celebration Meets Caution: Long Acting Reversible Contraception (LARC)’s Boons, Potential Busts, and the Benefits of a Reproductive Justice Approach

    PubMed Central

    Higgins, Jenny A.

    2014-01-01

    Recent years have witnessed an outpouring of research and funding pertaining to long-acting reversible contraception (LARC). The time is ripe to contextualize LARC’s hype within our broader reproductive health goals and tools—that is, how we can best address the needs of individuals who benefit from the reproductive health services we provide. After reviewing LARC’s major benefits, this commentary presents three potentially problematic aspects of LARC promotion: 1) the notion that increasing LARC use could singlehandedly end unintended pregnancies and their associations with poverty, 2) the clinical emphasis on LARC methods over all others, and 3) inadvertently failing to acknowledge the ways in which poor women of color will experience LARC promotion through legacies of racism and eugenics. The comment concludes by highlighting the benefits of a reproductive justice approach to LARC: an approach devoted to making LARC affordable and accessible while simultaneously respecting women’s decisions not to use LARC, their ability to have LARC removed when they wish, and their ability to determine for themselves where contraception and pregnancies fit into their lives. PMID:24582293

  20. Application of Adaptive Design Methodology in Development of a Long-Acting Glucagon-Like Peptide-1 Analog (Dulaglutide): Statistical Design and Simulations

    PubMed Central

    Skrivanek, Zachary; Berry, Scott; Berry, Don; Chien, Jenny; Geiger, Mary Jane; Anderson, James H.; Gaydos, Brenda

    2012-01-01

    Background Dulaglutide (dula, LY2189265), a long-acting glucagon-like peptide-1 analog, is being developed to treat type 2 diabetes mellitus. Methods To foster the development of dula, we designed a two-stage adaptive, dose-finding, inferentially seamless phase 2/3 study. The Bayesian theoretical framework is used to adaptively randomize patients in stage 1 to 7 dula doses and, at the decision point, to either stop for futility or to select up to 2 dula doses for stage 2. After dose selection, patients continue to be randomized to the selected dula doses or comparator arms. Data from patients assigned the selected doses will be pooled across both stages and analyzed with an analysis of covariance model, using baseline hemoglobin A1c and country as covariates. The operating characteristics of the trial were assessed by extensive simulation studies. Results Simulations demonstrated that the adaptive design would identify the correct doses 88% of the time, compared to as low as 6% for a fixed-dose design (the latter value based on frequentist decision rules analogous to the Bayesian decision rules for adaptive design). Conclusions This article discusses the decision rules used to select the dula dose(s); the mathematical details of the adaptive algorithm—including a description of the clinical utility index used to mathematically quantify the desirability of a dose based on safety and efficacy measurements; and a description of the simulation process and results that quantify the operating characteristics of the design. PMID:23294775

  1. Paliperidone palmitate in non-acute patients with schizophrenia previously unsuccessfully treated with risperidone long-acting therapy or frequently used conventional depot antipsychotics

    PubMed Central

    Bergmans, P; Cherubin, P; Keim, S; Llorca, P-M; Cosar, B; Petralia, A; Corrivetti, G; Hargarter, L

    2015-01-01

    PALMFlexS, a prospective multicentre, open-label, 6-month, phase IIIb interventional study, explored tolerability, safety and treatment response in adults (n = 231) with non-acute but symptomatic schizophrenia switching to flexibly dosed paliperidone palmitate (PP) after unsuccessful treatment with risperidone long-acting injectable therapy (RLAT) or conventional depot antipsychotics (APs). Treatment response was measured by change in Positive and Negative Syndrome Scale (PANSS) total score from baseline (BL) to last-observation-carried-forward (LOCF) endpoint (EP). Safety and tolerability assessments included Extrapyramidal Symptom Rating Scale (ESRS) total score and treatment-emergent adverse events. Significant reductions in mean PANSS total score were observed for all groups (−7.5 to −10.6; p ⩽ 0.01 [BL to LOCF EP]). After switching to PP, more than 50% of all patients achieved ⩾20% and one-third of RLAT-treated patients even achieved ⩾50% improvement in PANSS total score. Across groups, there were significant improvements (p < 0.05) in symptom severity as measured by Clinical Global Impression-Severity (CGI-S; trend for improvement with RLAT; p = 0.0568), subjective well-being, medication satisfaction, and patient functioning with PP. PP was generally well tolerated. Clinically relevant benefits were observed in non-acute patients with schizophrenia switched from RLAT or conventional depot APs to PP. PMID:25999398

  2. Assessment of pharmacokinetic compatibility of short acting CDRI candidate trioxane derivative, 99-411, with long acting prescription antimalarials, lumefantrine and piperaquine.

    PubMed

    Taneja, Isha; Raju, Kanumuri Siva Rama; Singh, Sheelendra Pratap; Wahajuddin, Muhammad

    2015-01-01

    The pharmacokinetic compatibility of short-acting CDRI candidate antimalarial trioxane derivative, 99-411, was tested with long-acting prescription antimalarials, lumefantrine and piperaquine. LC-ESI-MS/MS methods were validated for simultaneous bioanalysis of lumefantrine and 99-411 and of piperaquine and 99-411 combinations. The interaction studies were performed in rats using these validated methods. The total systemic exposure of 99-411 increased when administered with either lumefantrine or piperaquine. However, co-administration of 99-411 significantly decreased the systemic exposure of piperaquine by half-fold while it had no effect on the kinetics of lumefantrine. 99-411, thus, seemed to be a good alternative to artemisinin derivatives for combination treatment with lumefantrine. To explore the reason for increased plasma levels of 99-411, an in situ permeability study was performed by co-perfusing lumefantrine and 99-411. In presence of lumefantrine, the absorption of 99-411 was significantly increased by 1.37 times than when given alone. Lumefantrine did not affect the metabolism of 99-411 when tested in vitro in human liver microsomes. Additionally, ATPase assay suggest that 99-411 was a substrate of human P-gp, thus, indicating the probability of interaction at the absorption level in humans as well. PMID:26602250

  3. Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase.

    PubMed

    Melody, Kevin; McBeth, Sarah; Kline, Christopher; Kashuba, Angela D M; Mellors, John W; Ambrose, Zandrea

    2015-12-01

    Preexposure prophylaxis (PrEP) using antiretroviral drugs is effective in reducing the risk of human immunodeficiency virus type 1 (HIV-1) infection, but adherence to the PrEP regimen is needed. To improve adherence, a long-acting injectable formulation of the nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV LA) has been developed. However, there are concerns that PrEP may select for drug-resistant mutations during preexisting or breakthrough infections, which could promote the spread of drug resistance and limit options for antiretroviral therapy. To address this concern, we administered RPV LA to macaques infected with simian immunodeficiency virus containing HIV-1 RT (RT-SHIV). Peak plasma RPV levels were equivalent to those reported in human trials and waned over time after dosing. RPV LA resulted in a 2-log decrease in plasma viremia, and the therapeutic effect was maintained for 15 weeks, until plasma drug concentrations dropped below 25 ng/ml. RT mutations E138G and E138Q were detected in single clones from plasma virus in separate animals only at one time point, and no resistance mutations were detected in viral RNA isolated from tissues. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities in vitro, whereas E138G conferred 2-fold resistance to RPV. Overall, selection of RPV-resistant variants was rare in an RT-SHIV macaque model despite prolonged exposure to slowly decreasing RPV concentrations following injection of RPV LA. PMID:26438501

  4. Is Household Wealth Associated With Use of Long-Acting Reversible and Permanent Methods of Contraception? A Multi-Country Analysis.

    PubMed

    Ugaz, Jorge I; Chatterji, Minki; Gribble, James N; Banke, Kathryn

    2016-03-01

    As programs continue to expand access to family planning information, services, and products, it is critical that these efforts be undertaken with an equity lens, ensuring that regardless of socioeconomic status, all women and couples can use the method that meets their needs. This study explores the relationship between household wealth and the use of long-acting and permanent methods (LAPMs) versus short-acting methods of contraception among modern method users, using multivariate analyses based on Demographic Health Survey data from 30 developing countries conducted between 2006 and 2013. Overall, and controlling for relevant individual and household characteristics including age, number of living children, education, and urban/rural residence, we found that wealthier women were more likely than poorer women to use LAPMs instead of short-acting methods: 20 of the 30 countries showed a positive and statistically significant association between wealth and LAPM use. For 10 of those countries, however, LAPM use was significantly higher only for the top (1 or 2) wealthiest quintiles. Eight countries showed no broad pattern of association, while in 2 countries-Bangladesh and India-poorer women were more likely to use LAPMs than wealthier women. The positive association between wealth and LAPM use was found most consistently in the Latin American and the Caribbean countries in our sample. These findings can help program implementers respond better to women's needs for modern contraception, especially in reaching women from lower- and middle-income households.

  5. Management of asthma and chronic obstructive pulmonary disease with combination inhaled corticosteroids and long-acting β-agonists: a review of comparative effectiveness research.

    PubMed

    Mapel, Douglas W; Roberts, Melissa H

    2014-05-01

    The value of combination therapy with inhaled corticosteroids and long-acting β-agonists (ICS/LABA) is well recognized in the management of asthma and chronic obstructive pulmonary disease (COPD). Despite differences in the pharmacological properties between two well-established ICS/LABA products (budesonide/formoterol and fluticasone/salmeterol), data from randomized clinical trials (RCTs) and meta-analyses suggest that these two products perform similarly under RCT conditions. In contrast, a few recently reported real-world comparative effectiveness studies have suggested that there are substantial differences between ICS/LABA combination treatments in terms of clinical and healthcare outcomes in patients with asthma or COPD. The purpose of this article is to provide a brief review of the benefits, as well as the limitations, of comparative effectiveness research (CER) in the therapeutic area of asthma and COPD. We conducted a structured literature review of the current CER studies on ICS/LABA combinations in asthma and COPD. These articles were then used to illustrate the unique challenges of CER studies, providing a summary of study results and limitations. We focus particularly on difficult biases and confounding factors that may be introduced before, during, and after the initiation of therapy. Beyond being a review of these two ICS/LABA combination treatments, this article is intended to help those who wish to assess the quality of CER published projects in asthma and COPD, or guide investigators who wish to design new CER studies for chronic respiratory disease treatments.

  6. Ethical issues experienced by mental health nurses in the administration of antipsychotic depot and long-acting intramuscular injections: a qualitative study.

    PubMed

    Smith, James Paul; Herber, Oliver Rudolf

    2015-06-01

    The ethical issues experienced by mental health nurses in administering antipsychotic depot and long-acting intramuscular injections (LAI) were explored in the present study. Mental health nurses face ethically-difficult situations when administering these medications. A phenomenological research method guided by Max van Manen's human science approach describes and interprets the ethical issues involved in performing the procedure. Purposive and snowball sampling was used to select eight participants from two mental health hospitals. Semistructured interviews were carried out to collect data. A thematic analysis was conducted on the data. The four main themes that emerged from the analyses were: (i) lack of alternatives; (ii) safety; (iii) feeling uncomfortable; and (iv) difficulty maintaining the therapeutic relationship. The findings suggest that mental health nurses face ethical challenges in administering LAI. The findings raise much needed awareness of the need for mental health nurses and nurse educators to consider the ethical issues experienced while performing the procedure. There is a need for nurse education providers and organizations to provide opportunities for mental health nurses to address their 'lived experiences'. Educational courses are needed to equip mental health nurses with the technical and critical thinking skills to administer safe and effective antipsychotic depot and LAI.

  7. Oral insulin--a perspective.

    PubMed

    Raj, N K Kavitha; Sharma, Chandra P

    2003-01-01

    Diabetes mellitus is generally controlled quite well with the administration of oral medications or by the use of insulin injections. The current practice is the use of one or more doses, intermediate or long acting insulin per day. Oral insulin is a promising yet experimental method providing tight glycemic control for patients with diabetes. A biologically adhesive delivery systems offer important advantage over conventional drug delivery systems. The engineered polymer microspheres made of erodable polymer display strong adhesive interactions with gastrointestinal mucus and cellular lining can traverse both the mucosal epithelium and the follicle associated epithelium covering the lymphoid tissue of Peyer's patches. Alginate, a natural polymer recovered from seaweed is being developed as a nanoparticle for the delivery of insulin without being destroyed in the stomach. Alginate is in fact finding application in biotechnology industry as thickening agent, a gelling agent and a colloid stabilizer. Alginate has in addition, several other properties that have enabled it to be used as a matrix for entrapment and for the delivery of a variety of proteins such as insulin and cells. These properties include: a relatively inert aqueous environment within the matrix; a mild room temperature encapsulation process free of organic solvents; a high gel porosity which allows for high diffusion rates of macromolecules; the ability to control this porosity with simple coating procedures and dissolution and biodegradation of the system under normal physiological conditions.

  8. Skeletal muscle oxidative metabolism in an animal model of pulmonary emphysema: formoterol and skeletal muscle dysfunction.

    PubMed

    Sullo, Nikol; Roviezzo, Fiorentina; Matteis, Maria; Spaziano, Giuseppe; Del Gaudio, Stefania; Lombardi, Assunta; Lucattelli, Monica; Polverino, Francesca; Lungarella, Giuseppe; Cirino, Giuseppe; Rossi, Francesco; D'Agostino, Bruno

    2013-02-01

    Skeletal muscle dysfunction is a significant contributor to exercise limitation in pulmonary emphysema. This study investigated skeletal muscle oxidative metabolism before and after aerosol exposure to a long-acting β-agonist (LABA), such as formoterol, in the pallid mouse (B6.Cg-Pldnpa/J), which has a deficiency in serum α(1)-antitrypsin (α(1)-PI) and develops spontaneous pulmonary emphysema. C57 BL/6J and its congener pallid mice of 8-12 and 16 months of age were treated with vehicle or formoterol aerosol challenge for 120 seconds. Morphological and morphometric studies and evaluations of mitochondrial adenosine diphosphate-stimulated respiration and of cytochrome oxidase activity on skeletal muscle were performed. Moreover, the mtDNA content in skeletal muscle and the mediators linked to muscle mitochondrial function and biogenesis, as well as TNF-α and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), were also evaluated. The lungs of pallid mice at 12 and 16 months of age showed patchy areas of airspace enlargements, with the destruction of alveolar septa. No significant differences were observed in basal values of mitochondrial skeletal muscle oxidative processes between C57 BL/6J and pallid mice. Exposure to LABA significantly improved mitochondrial skeletal muscle oxidative processes in emphysematous mice, where the mtDNA content was significantly higher with respect to 8-month-old pallid mice. This effect was compared with a significant increase of PGC-1α in skeletal muscles of 16-month-old pallid mice, with no significant changes in TNF-α concentrations. In conclusion, in emphysematous mice that showed an increased mtDNA content, exposure to inhaled LABA can improve mitochondrial skeletal muscle oxidative processes. PGC-1α may serve as a possible mediator of this effect.

  9. Nonspeech Oral Movements and Oral Motor Disorders: A Narrative Review

    PubMed Central

    2015-01-01

    Purpose Speech and other oral functions such as swallowing have been compared and contrasted with oral behaviors variously labeled quasispeech, paraspeech, speechlike, and nonspeech, all of which overlap to some degree in neural control, muscles deployed, and movements performed. Efforts to understand the relationships among these behaviors are hindered by the lack of explicit and widely accepted definitions. This review article offers definitions and taxonomies for nonspeech oral movements and for diverse speaking tasks, both overt and covert. Method Review of the literature included searches of Medline, Google Scholar, HighWire Press, and various online sources. Search terms pertained to speech, quasispeech, paraspeech, speechlike, and nonspeech oral movements. Searches also were carried out for associated terms in oral biology, craniofacial physiology, and motor control. Results and Conclusions Nonspeech movements have a broad spectrum of clinical applications, including developmental speech and language disorders, motor speech disorders, feeding and swallowing difficulties, obstructive sleep apnea syndrome, trismus, and tardive stereotypies. The role and benefit of nonspeech oral movements are controversial in many oral motor disorders. It is argued that the clinical value of these movements can be elucidated through careful definitions and task descriptions such as those proposed in this review article. PMID:26126128

  10. Oral cysticercosis.

    PubMed

    Chunduri, Nagendra S; Goteki, Venkateswarulu; Gelli, Vamsi; Madasu, Krishnaveni

    2013-03-01

    Cysticercosis is a common disease in developing countries, but oral lesions caused by this parasitic infestation are rare. We report here a rare case of oral cysticercosis in a 17 year old male who sought treatment for an asymptomatic nodule of the lower lip that had previously been diagnosed as a mucocele. PMID:23691623

  11. The effects of a long-acting progestin on the hypothalamic-pituitary-ovarian axis in women with normal menstrual cycles.

    PubMed

    Poindexter, A N; Dildy, G A; Brody, S A; Snabes, M C; Brodyand, S A

    1993-07-01

    This study was performed to determine how a long-acting, slow-release preparation of norethindrone (NET) affects the hypothalamic-pituitary-ovarian axis of normal ovulatory women. Ten women were studied during the luteal phase of their menstrual cycle, and again at six and twelve weeks following intramuscular administration of 100 mg NET microencapsulated in poly-D,L-lactide-co-glycolide. Serial LH samples, serum E, P, and NET were followed by a GnRH stimulation test. Compared to luteal phase values, six and twelve weeks of treatment with NET inhibited serum E2 and P while mean serum LH remained unchanged and mean serum FSH increased significantly (p < 0.05). LH pulse frequency after NET treatment was twice the rate (p < 0.01) as that of the luteal phase, whereas LH pulse amplitude was decreased significantly (p < 0.05). Finally, although there was no significant change in pituitary LH secretion in response to GnRH, NET treatment augmented FSH responsiveness to GnRH at the times studied. Preserved pituitary responsiveness to GnRH in NET-treated patients suggests that inhibited ovarian function results in an increase in GnRH pulse frequency but not GnRH pulse amplitude. Since the progestational milieu is maintained in these patients by NET treatment, the decrease in serum E2 may be responsible for the increase in GnRH pulse frequency. The presence of a critical level of E2 may be necessary for progestins to affect the hypothalamic GnRH pulse generator.

  12. Comparative efficacy of inhaled corticosteroid and long-acting beta agonist combinations in preventing COPD exacerbations: a Bayesian network meta-analysis

    PubMed Central

    Oba, Yuji; Lone, Nazir A

    2014-01-01

    Background A combination therapy with inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations. Currently, there are five ICS/LABA combination products available on the market. The purpose of this study was to systematically review the efficacy of various ICS/LABA combinations with a network meta-analysis. Methods Several databases and manufacturer’s websites were searched for relevant clinical trials. Randomized control trials, at least 12 weeks duration, comparing an ICS/LABA combination with active control or placebo were included. Moderate and severe exacerbations were chosen as the outcome assessment criteria. The primary analyses were conducted with a Bayesian Markov chain Monte Carlo method. Results Most of the ICS/LABA combinations reduced moderate-to-severe exacerbations as compared with placebo and LABA, but none of them reduced severe exacerbations. However, many studies excluded patients receiving long-term oxygen therapy. Moderate-dose ICS was as effective as high-dose ICS in reducing exacerbations when combined with LABA. Conclusion ICS/LABA combinations had a class effect with regard to the prevention of COPD exacerbations. Moderate-dose ICS/LABA combination therapy would be sufficient for COPD patients when indicated. The efficacy of ICS/LABA combination therapy appeared modest and had no impact in reducing severe exacerbations. Further studies are needed to evaluate the efficacy of ICS/LABA combination therapy in severely affected COPD patients requiring long-term oxygen therapy. PMID:24872685

  13. Impact of extrafine formulations of inhaled corticosteroids/long-acting beta-2 agonist combinations on patient-related outcomes in asthma and COPD

    PubMed Central

    Scichilone, Nicola; Benfante, Alida; Morandi, Luca; Bellini, Federico; Papi, Alberto

    2014-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are among the most common chronic diseases worldwide, characterized by a condition of variable degree of airway obstruction and chronic airway inflammation. A large body of evidence has demonstrated the importance of small airways as a pharmacological target in these clinical conditions. Despite a deeper understanding of the pathophysiological mechanisms, the epidemiological observations show that a significant proportion of asthmatic and COPD patients have a suboptimal (or lack of) control of their diseases. Different factors could influence the effectiveness of inhaled treatment in chronic respiratory diseases: patient-related (eg, aging); disease-related (eg, comorbid conditions); and drug-related/formulation-related factors. The presence of multiple illnesses is common in the elderly patient as a result of two processes: the association between age and incidence of degenerative diseases; and the development over time of complications of the existing diseases. In addition, specific comorbidities may contribute to impair the ability to use inhalers, such as devices for efficient drug delivery in the respiratory system. The inability to reach and treat the peripheral airways may contribute to the lack of efficacy of inhaled treatments. The recent development of inhaled extrafine formulations allows a more uniform distribution of the inhaled treatment throughout the respiratory tree to include the peripheral airways. The beclomethasone/formoterol extrafine formulation is available for the treatment of asthma and COPD. Different biomarkers of peripheral airways are improved by beclomethasone/formoterol extrafine treatment in comparison with equivalent nonextrafine inhaled corticosteroids/long-acting beta-2 agonist (ICS/LABA) combinations. These improvements are associated with improved lung function and clinical outcomes, along with reduced systemic exposure to inhaled corticosteroids. The increased knowledge

  14. Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations

    SciTech Connect

    Mason-Garcia, M.; Vigh, S.; Comaru-Schally, A.M.; Redding, T.W.; Somogyvari-Vigh, A.; Horvath, J.; Schally, A.V.

    1985-03-01

    A sensitive and specific radioimmunoassay for (6-D-tryptophan)luteinizing hormone-releasing hormone ((D-Trp/sup 6/)LH-RH) was developed and used for following the rate of liberation of (D-Trp/sup 6/)LH-RH from a long-acting delivery systems based on a microcapsule formulation. Rabbit antibodies were generated against (D-Trp/sup 6/)LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant cross-reactivity with other peptides. The minimal detectable dose of (D-Trp/sup 6/)LH-RH was 2 pg per tube. In tra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of (D-Trp/sup 6/)LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after one-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 ..mu..g of the peptide, serum (D-Trp/sup 6/)LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of (D-Trp/sup 6/)LH-RH was followed. The improved batch of microcapsules of (D-Trp/sup 6/)LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection.

  15. Induction of regulator of G-protein signaling 2 expression by long-acting β2-adrenoceptor agonists and glucocorticoids in human airway epithelial cells.

    PubMed

    Holden, Neil S; George, Tresa; Rider, Christopher F; Chandrasekhar, Ambika; Shah, Suharsh; Kaur, Manminder; Johnson, Malcolm; Siderovski, David P; Leigh, Richard; Giembycz, Mark A; Newton, Robert

    2014-01-01

    In asthma and chronic obstructive pulmonary disease (COPD) multiple mediators act on Gαq-linked G-protein-coupled receptors (GPCRs) to cause bronchoconstriction. However, acting on the airway epithelium, such mediators may also elicit inflammatory responses. In human bronchial epithelial BEAS-2B cells (bronchial epithelium + adenovirus 12-SV40 hybrid), regulator of G-protein signaling (RGS) 2 mRNA and protein were synergistically induced in response to combinations of long-acting β2-adrenoceptor agonist (LABA) (salmeterol, formoterol) plus glucocorticoid (dexamethasone, fluticasone propionate, budesonide). Equivalent responses occurred in primary human bronchial epithelial cells. Concentrations of glucocorticoid plus LABA required to induce RGS2 expression in BEAS-2B cells were consistent with the levels achieved therapeutically in the lungs. As RGS2 is a GTPase-activating protein that switches off Gαq, intracellular free calcium ([Ca(2+)]i) flux was used as a surrogate of responses induced by histamine, methacholine, and the thromboxane receptor agonist U46619 [(Z)-7-[(1S,4R,5R,6S)-5-[(E,3S)-3-hydroxyoct-1-enyl]-3-oxabicyclo[2.2.1]heptan-6-yl]hept-5-enoic acid]. This was significantly attenuated by salmeterol plus dexamethasone pretreatment, or RGS2 overexpression, and the protective effect of salmeterol plus dexamethasone was abolished by RGS2 RNA silencing. Although methacholine and U46619 induced interleukin-8 (IL-8) release and this was inhibited by RGS2 overexpression, the repression of U46619-induced IL-8 release by salmeterol plus dexamethasone was unaffected by RGS2 knockdown. Given a role for Gαq-mediated pathways in inducing IL-8 release, we propose that RGS2 acts redundantly with other effector processes to repress IL-8 expression. Thus, RGS2 expression is a novel effector mechanism in the airway epithelium that is induced by glucocorticoid/LABA combinations. This could contribute to the efficacy of glucocorticoid/LABA combinations in asthma and

  16. The Use of Long Acting Reversible Contraceptives and the Relationship between Discontinuation Rates due to Menopause and to Female and Male Sterilizations.

    PubMed

    Ferreira, Jessica Mayra; Monteiro, Ilza; Castro, Sara; Villarroel, Marina; Silveira, Carolina; Bahamondes, Luis

    2016-05-01

    Introduction Women require effective contraception until they reach menopause. The long acting reversible contraceptives (LARC) and the depot-medroxyprogesterone acetate (DMPA, Depo-Provera®, Pfizer, Puurs, Belgium) are great options and can replace possible sterilizations. Purpose To assess the relationship between the use of LARCs and DMPA and terminations ascribed to menopause and sterilizations in a Brazilian clinic. Methods We reviewed the records of women between 12 and 50 years of age attending the clinic that chose to use a LARC method or DMPA. Cumulative termination rates due to sterilization or because the woman had reached menopause were computed using single decrement life-table analysis over 32 years. We also examined all records of surgical sterilization at our hospital between the years 1980-2012. Results Three hundred thirty-two women had continuously used the same contraceptive until menopause, and 555 women had discontinued the method because they or their partners underwent sterilization. From year 20 to year 30 of use, levonorgestrel intrauterine-releasing system (LNG-IUS - Mirena®, Bayer Oy, Turku, Finland; available since 1980), copper intrauterine device (IUD - available since 1980) and DMPA users showed a trend of cumulative higher discontinuation rates due to menopause when compared with the discontinuation rates due to sterilization. Over the study period, a steep decline in the use of sterilization occurred. Conclusion Over the past 15 years of research we have observed a trend: women usually preferred to continue using LARC methods or DMPA until menopause rather than decide for sterilization, be it their own, or their partners'. The annual number of sterilizations dropped in the same period. The use of LARC methods and DMPA until menopause is an important option to avoid sterilization, which requires a surgical procedure with potential complications. PMID:27187927

  17. Resource utilization in patients with schizophrenia who initiated risperidone long-acting therapy: results from the Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation (SOURCE)

    PubMed Central

    2011-01-01

    Background Schizophrenia is a chronic mental health disorder associated with increased hospital admissions and excessive utilization of outpatient services and long-term care. This analysis examined health care resource utilization from a 24-month observational study of patients with schizophrenia initiated on risperidone long-acting therapy (RLAT). Methods Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation (SOURCE) was a 24-month observational study designed to examine real-world treatment outcomes by prospectively following patients with schizophrenia initiated on RLAT. At baseline visit, prior hospitalization and ER visit dates were obtained for the previous 12 months and subsequent hospitalization visit dates were obtained at 3-month visits, if available. The health care resource utilization outcomes measures observed in this analysis were hospitalizations for any reason, psychiatric-related hospitalizations, and emergency room (ER) visits. Incidence density analysis was used to assess pre-event and postevent rates per person-year (PY). Results The primary medical resource utilization analysis included 435 patients who had a baseline visit, ≥1 postbaseline visits after RLAT initiation, and valid hospitalization dates. The number of hospitalizations and ER visits per PY declined significantly (p < .0001) after initiation with RLAT. A 41% decrease (difference of -0.29 hospitalizations per PY [95% CI: -0.39 to -0.18] from baseline) in hospitalizations for any reason, a 56% decrease (a difference of -0.35 hospitalizations per PY [95% CI: -0.44 to -0.26] from baseline) in psychiatric-related hospitalizations, and a 40% decrease (-0.26 hospitalizations per PY [95% CI: -0.44 to -0.10] from baseline) in ER visits were observed after the baseline period. The percentage of psychiatric-related hospitalizations decreased significantly after RLAT initiation, and patients had fewer inpatient hospitalizations and ER visits (all p < .0001). Conclusion The

  18. Long-Acting PASylated Leptin Ameliorates Obesity by Promoting Satiety and Preventing Hypometabolism in Leptin-Deficient Lep(ob/ob) Mice.

    PubMed

    Bolze, Florian; Morath, Volker; Bast, Andrea; Rink, Nadine; Schlapschy, Martin; Mocek, Sabine; Skerra, Arne; Klingenspor, Martin

    2016-01-01

    Body weight loss of Lep(ob/ob) mice in response to leptin is larger than expected from the reduction in energy intake alone, suggesting a thermogenic action of unknown magnitude. We exploited the superior pharmacological properties of a novel long-acting leptin prepared via PASylation to study the contribution of its anorexigenic and thermogenic effects. PASylation, the genetic fusion of leptin with a conformationally disordered polypeptide comprising 600 Pro/Ala/Ser (PAS) residues, provides a superior way to increase the hydrodynamic volume of the fusion protein, thus retarding kidney filtration and extending plasma half-life. Here a single PAS(600)-leptin injection (300 pmol/g) resulted in a maximal weight reduction of 21% 6 days after application. The negative energy balance of 300 kJ/(4 d) was driven by a decrease in energy intake, whereas energy expenditure remained stable. Mice that were food restricted to the same extent showed an energy deficit of only 220 kJ/(4 d) owing to recurring torpor bouts. Therefore, the anorexigenic effect of PAS(600)-leptin contributes 75% to weight loss, whereas the thermogenic action accounts for 25% by preventing hypometabolism. In a second experiment, just four injections of PAS(600)-leptin (100 pmol/g) administered in 5- to 6-day intervals rectified the Lep(ob/ob) phenotype. In total, 16 nmol of PAS(600)-leptin per mouse triggered a weight loss of 43% within 20 days and normalized hypothermia and glucose homeostasis as well as hepatic steatosis. The beneficial properties of PAS(600)-leptin are substantiated by a comparison with previous studies in which approximately 400 nmol (∼25-fold) unmodified leptin was mandatory to achieve similar improvements.

  19. Long-Acting PASylated Leptin Ameliorates Obesity by Promoting Satiety and Preventing Hypometabolism in Leptin-Deficient Lep(ob/ob) Mice.

    PubMed

    Bolze, Florian; Morath, Volker; Bast, Andrea; Rink, Nadine; Schlapschy, Martin; Mocek, Sabine; Skerra, Arne; Klingenspor, Martin

    2016-01-01

    Body weight loss of Lep(ob/ob) mice in response to leptin is larger than expected from the reduction in energy intake alone, suggesting a thermogenic action of unknown magnitude. We exploited the superior pharmacological properties of a novel long-acting leptin prepared via PASylation to study the contribution of its anorexigenic and thermogenic effects. PASylation, the genetic fusion of leptin with a conformationally disordered polypeptide comprising 600 Pro/Ala/Ser (PAS) residues, provides a superior way to increase the hydrodynamic volume of the fusion protein, thus retarding kidney filtration and extending plasma half-life. Here a single PAS(600)-leptin injection (300 pmol/g) resulted in a maximal weight reduction of 21% 6 days after application. The negative energy balance of 300 kJ/(4 d) was driven by a decrease in energy intake, whereas energy expenditure remained stable. Mice that were food restricted to the same extent showed an energy deficit of only 220 kJ/(4 d) owing to recurring torpor bouts. Therefore, the anorexigenic effect of PAS(600)-leptin contributes 75% to weight loss, whereas the thermogenic action accounts for 25% by preventing hypometabolism. In a second experiment, just four injections of PAS(600)-leptin (100 pmol/g) administered in 5- to 6-day intervals rectified the Lep(ob/ob) phenotype. In total, 16 nmol of PAS(600)-leptin per mouse triggered a weight loss of 43% within 20 days and normalized hypothermia and glucose homeostasis as well as hepatic steatosis. The beneficial properties of PAS(600)-leptin are substantiated by a comparison with previous studies in which approximately 400 nmol (∼25-fold) unmodified leptin was mandatory to achieve similar improvements. PMID:26492472

  20. Efficacy of moxidectin long-acting injectable formulation (1 mg/kg bodyweight) against first instar larvae of Oestrus ovis in naturally infected sheep.

    PubMed

    Martínez-Valladares, M; Valcárcel, F; Álvarez-Sánchez, M A; Cordero-Pérez, C; Fernández-Pato, N; Frontera, E; Meana, A; Rojo-Vázquez, F A

    2013-03-31

    The objective of the current study was to evaluate the efficacy of a single treatment with a long-acting injectable formulation of moxidectin (MOX) at 1.0 mg/kg bodyweight (b.w.) against natural infection by nasal bots (Oestrus ovis) in sheep with special attention to first instar larvae (L1). Firstly, a local farm with clinical history of oestrosis was chosen to conduct the assay. A total of 49 sheep were pre-selected at the end of the summer according to the presence of evident clinical signs of infection and confirmed later by means of an indirect ELISA against excretory-secretory products from L1 to detect IgG antibodies. After that, 24 sheep were chosen to carry out the study on the basis of positive serology and age since the oldest ones were selected. The day 0 of the assay, the treatment group was administered with the MOX formulation by subcutaneous injection at the base of the left ear and the control group was administered with a saline solution in the same way. All sheep were slaughtered on day 28 post-treatment (pt). At the necropsy, the head of all sheep were cut off and split into two sagital sections and all larvae from nasal passages, septum, middle meatus, conchae and sinuses were recovered. After the necropsy, a significant number of L1 was only found in the control group and therefore the efficacy of the MOX formulation was only calculated against this stage. As a result, the formulation was 90.2% effective against L1 for sheep slaughtered at day 28 pt. PMID:23333136

  1. The long-acting β2-adrenoceptor agonist, indacaterol, enhances glucocorticoid receptor-mediated transcription in human airway epithelial cells in a gene- and agonist-dependent manner

    PubMed Central

    Joshi, T; Johnson, M; Newton, R; Giembycz, M A

    2015-01-01

    Background and Purpose Inhaled glucocorticoid (ICS)/long-acting β2-adrenoceptor agonist (LABA) combination therapy is a recommended treatment option for patients with moderate/severe asthma in whom adequate control cannot be achieved by an ICS alone. Previously, we discovered that LABAs can augment dexamethasone-inducible gene expression and proposed that this effect may explain how these two drugs interact to deliver superior clinical benefit. Herein, we extended that observation by analysing, pharmacodynamically, the effect of the LABA, indacaterol, on glucocorticoid receptor (GR)-mediated gene transcription induced by seven ligands with intrinsic activity values that span the spectrum of full agonism to antagonism. Experimental Approach BEAS-2B human airway epithelial cells stably transfected with a 2× glucocorticoid response element luciferase reporter were used to model gene transcription together with an analysis of several glucocorticoid-inducible genes. Key Results Indacaterol augmented glucocorticoid-induced reporter activation in a manner that was positively related to the intrinsic activity of the GR agonist. This effect was demonstrated by an increase in response maxima without a change in GR agonist affinity or efficacy. Indacaterol also enhanced glucocorticoid-inducible gene expression. However, the magnitude of this effect was dependent on both the GR agonist and the gene of interest. Conclusions and Implications These data suggest that indacaterol activates a molecular rheostat, which increases the transcriptional competency of GR in an agonist- and gene-dependent manner without apparently changing the relationship between fractional GR occupancy and response. These findings provide a platform to rationally design ICS/LABA combination therapy that is based on the generation of agonist-dependent gene expression profiles in target and off-target tissues. PMID:25598440

  2. Effectiveness and safety of a long-acting, once-daily, two-phase release formulation of methylphenidate (Ritalin ® LA) in school children under daily practice conditions.

    PubMed

    Haertling, Fabian; Mueller, Beate; Bilke-Hentsch, Oliver

    2015-06-01

    Long-acting (LA) preparations of methylphenidate allow for once-daily dosing; however, pharmacokinetics may vary and depend on food intake. The objective was to evaluate effectiveness of a two-phase release formulation (Ritalin(®) LA) under daily practice conditions. This was a prospective, multicenter, observational study in Germany. Eligibility and dosing were determined by the physician based on the drug label. Outcomes included changes over 3 months of treatment in assessments of effect duration, clinical global impression (CGI), and quality of life (ILK). In 101 sites, 262 patients (197 boys, 63 girls, and two unknown) with a mean age of 10.9 years were enrolled; 50 were treated for the first time; 212 switched medication to Ritalin(®) LA. After 3 months, CGI improved in 59.4 % of patients, and well-being overall was rated as good by 61.0 % of parents and 63.7 % of children. Based on parents' assessment, the proportion of children suffering from strong disease burden decreased from 40.7 to 15.1 %. In 123 insufficient responders to previous ADHD medications, benefit from Ritalin(®) LA was above average and effect duration was significantly prolonged as compared to pretreatment. Overall, 28 patients (10.7 %) had treatment-related adverse events with one case being serious; 23 patients (8.8 %) discontinued therapy, 7 (2.7 %) due to poor treatment response; and 212 patients (81 %) continued treatment beyond the study. In line with clinical trial data, Ritalin(®) LA provides significant benefit also under routine practice conditions.

  3. Effect of long-acting gonadotropin-releasing hormone analog (leuprolide) therapy on prostatic size and symptoms in 15 men with benign prostatic hypertrophy.

    PubMed

    Gabrilove, J L; Levine, A C; Kirschenbaum, A; Droller, M

    1989-09-01

    To determine the effects of reversible medical castration on prostatic size and symptoms we treated 15 patients with benign prostatic hypertrophy with a long-acting GnRH analog, leuprolide (1 mg/day sc), for a minimum of 4 months. The men's serum testosterone, dihydrotestosterone, and estradiol concentrations fell to very low levels within 4-6 weeks after the initiation of treatment. Transrectal ultrasonography of the prostate demonstrated an average shrinkage of 40% after 4 months of treatment (n = 15) and 46% after 6 months of treatment (n = 11). All 15 men had improvement in urinary flow and, to a lesser extent, in nocturia and frequency. The side-effects of the therapy were decreased potency and flushing. The most dramatic improvement occurred in 4 of the 5 men who had complete urinary obstruction before treatment. One man had a suprapubic cystotomy tube removed during the fifth treatment month. Two other men who had Foley catheters before treatment are voiding well without catheters since their third treatment month. Another man who had a very large prostate (300 g) before treatment had one successful voiding trial, although he still has a suprapubic cystotomy tube. One man decided to stop treatment after 6 months. Two months later his hormone values and prostate size had returned to pretreatment levels. One man treated during the fourth and fifth months with fluoxymesterone in addition to leuprolide had regrowth of his prostate while receiving this androgen. We conclude that leuprolide treatment of men with benign prostatic hypertrophy results in shrinkage of prostatic size and concomitant improvement in the obstructive symptoms of prostatism. The prostatic shrinkage reverses when treatment is discontinued or combined with androgen. PMID:2474565

  4. Oral cenesthopathy.

    PubMed

    Umezaki, Yojiro; Miura, Anna; Watanabe, Motoko; Takenoshita, Miho; Uezato, Akihito; Toriihara, Akira; Nishikawa, Toru; Toyofuku, Akira

    2016-01-01

    Cenesthopathy is characterized by abnormal and strange bodily sensations and is classified as a 'delusional disorder, somatic type' or 'somatoform disorder' according to the DSM 5. The oral cavity is one of the frequent sites of cenesthopathy, thus the term 'oral cenesthopathy.' Patients with oral cenesthopathy complain of unusual sensations without corresponding abnormal findings in the oral area, such as excessive mucus secretion, a slimy sensation, or a feeling of coils or wires being present within the oral region. They usually visit multiple dentists rather than psychiatrists. Without a proper diagnosis, they repeatedly pursue unnecessary surgical procedures to remove their 'foreign body'. This sometimes creates a dilemma between the dentists and patients. The nosography of oral cenesthopathy has been discussed in some case reports and reviews but is overlooked in mainstream medicine. This review focuses on the various aspects of oral cenesthopathy. The estimated prevalence of cenesthopathy was 0.2 to 1.9 % in a study done at a Japanese university psychiatry clinic and 27 % in a study done at a Japanese psychosomatic dentistry clinic. Oral cenesthopathy do not have clear disposition, while some studies reported that elderly women were most commonly affected. Its pathophysiology has not been fully elucidated. However, recent studies have suggested a right > left asymmetrical pattern of the cerebral blood flow of patients with oral cenesthopathy. Antidepressants, antipsychotic drugs, electroconvulsive therapy, and psychotherapy might be effective in some cases, though it is known to be intractable. To date, the epidemiology, pathophysiology, etiology, classification and treatment of oral cenesthopathy are unknown due to the few reports on the disorder, though there are a few case reports. To overcome this difficult medical condition, clinico-statistical and case-control studies done under rigorous criteria and with a large sample size are required. PMID

  5. Injection of testosterone may be safer and more effective than transdermal administration for combating loss of muscle and bone in older men.

    PubMed

    Borst, Stephen E; Yarrow, Joshua F

    2015-06-15

    The value of testosterone replacement therapy (TRT) for older men is currently a topic of intense debate. While US testosterone prescriptions have tripled in the past decade (9), debate continues over the risks and benefits of TRT. TRT is currently prescribed for older men with either low serum testosterone (T) or low T plus accompanying symptoms of hypogonadism. The normal range for serum testosterone is 300 to 1,000 ng/dl. Serum T ≤ 300 ng/dl is considered to be low, and T ≤ 250 is considered to be frank hypogonadism. Most experts support TRT for older men with frank hypogonadism and symptoms. Treatment for men who simply have low T remains somewhat controversial. TRT is most frequently administered by intramuscular (im) injection of long-acting T esters or transdermally via patch or gel preparations and infrequently via oral administration. TRT produces a number of established benefits in hypogonadal men, including increased muscle mass and strength, decreased fat mass, increased bone mineral density, and improved sexual function, and in some cases those benefits are dose dependent. For example, doses of TRT administered by im injection are typically higher than those administered transdermally, which results in greater musculoskeletal benefits. TRT also produces known risks including development of polycythemia (Hct > 50) in 6% of those treated, decrease in HDL, breast tenderness and enlargement, prostate enlargement, increases in serum PSA, and prostate-related events and may cause suppression of the hypothalamic-pituitary-gonadal axis. Importantly, TRT does not increase the risk of prostate cancer. Putative risks include edema and worsening of sleep apnea. Several recent reports have also indicated that TRT may produce cardiovascular (CV) risks, while others report no risk or even benefit. To address the potential CV risks of TRT, we have recently reported via meta-analysis that oral TRT increases CV risk and suggested that the CV risk profile for im TRT

  6. An "enigmatic" L-carnosine (β-alanyl-L-histidine)? Cell proliferative activity as a fundamental property of a natural dipeptide inherent to traditional antioxidant, anti-aging biological activities: balancing and a hormonally correct agent, novel patented oral therapy dosage formulation for mobility, skeletal muscle power and functional performance, hypothalamic-pituitary- brain relationship in health, aging and stress studies.

    PubMed

    Babizhayev, Mark A; Yegorov, Yegor E

    2015-01-01

    Hypothalamic releasing and inhibiting hormones are major neuroendocrine regulators of human body metabolism being driven directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. The alternative physiological or therapeutic interventions utilizing the pharmaco-nutritional boost of imidazole-containing dipeptides (non-hydrolized oral form of carnosine, carcinine, N-acetylcarnosine lubricant eye drops) can maintain health, enhance physical exercise performance and prevent ageing. Carnosine (β-alanyl-L-histidine) is synthesized in mammalian skeletal muscle. There is an evidence that the release of carnosine from the skeletal muscle sarcomeres moieties during physical exercise affects autonomic neurotransmission and physiological functions. Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function. Carnosine and its imidazole-containing dipeptide derivatives are renowned for their anti-aging, antioxidant, membrane protective, metal ion chelating, buffering, anti-glycation/ transglycating activities used to prevent and treat a spectrum of age-related and metabolic diseases, such as neurodegenerative disease, sight threatening eye diseases, Diabetes mellitus and its complications, cancers and other disorders due to their wide spectrum biological activities. The precursor of carnosine (and related imidazole containing compounds) synthesis in skeletal muscles beta-alanine is used as the

  7. Quinidine Oral

    MedlinePlus

    ... medications for seizures, sleep, or an infection; and vitamins.tell your doctor if you have an infection or have or have ever had myasthenia gravis; heart, kidney, or liver disease; or muscle weakness.tell your doctor if you ...

  8. Buccinator muscle repositioning: a case report.

    PubMed

    Baghele, Om N; Baghele, Mangala O

    2012-09-01

    Anatomical abnormalities are frequently associated with problems. One such abnormality is crestal attachment of the frenum or muscle on the alveolar process. Crestal attachment of buccinator muscle is a rare phenomenon. It may cause various problems in routine oral exercises or restoring the edentulous area. Presented here is a case of abnormal buccinator muscle attachment, which was relocated apically by surgical means using an acrylic stent. The healing was uneventful, and significant apical repositioning was observed. The area was then considered for prosthodontic therapy. A fixed bridge was fabricated and the long-term results of the fixed bridge therapy were assured, because the patient could maintain oral hygiene well after the muscle repositioning operation.

  9. Hospitalization resource utilization and costs among Medicaid insured patients with schizophrenia with different treatment durations of long-acting injectable antipsychotic therapy.

    PubMed

    Bera, Rimal; Offord, Steve; Zubek, Donna; Lau, Gina; Lin, Jay; Karson, Craig

    2014-02-01

    This study evaluated the impact of using long-acting injectable (LAI) antipsychotics for a longer treatment duration versus a short duration on health care resource utilization among Medicaid-insured schizophrenia patients. Schizophrenia patients 13 years or older initiating LAI antipsychotics were identified from the Truven Health Analytics MarketScan Research Medicaid database between July 1, 2005, and June 30, 2010. The study population was grouped into 2 study cohorts (longer-usage-duration cohort: ≥ 180 days of supply and short-usage-duration cohort: <180 days of supply). Hospitalization-related resource utilization and costs were determined during a variable follow-up period and compared at the unadjusted and adjusted levels. Of the 5694 patients identified, 2838 patients were treated with LAI antipsychotics for a mean duration of 604 (SD, 432) days (mean age, 38.91 years), and 2856 were treated for 86 (SD, 43) days (mean age, 39.96 days). Total hospital lengths of stay, all cause (6.56 [SD, 18.63] vs 4.93 [SD, 13.40] days, P < 0.001) and schizophrenia related (5.18 [SD, 14.96] vs 4.16 [SD, 11.94] days, P = 0.005), and the mean number of hospitalizations, all cause (0.79 [SD, 1.78] vs 0.61 [SD, 1.41], P < 0.001) and schizophrenia related (0.63 [SD, 1.55] vs 0.51 [SD, 1.26], P = 0.001), were lower for the longer-usage-duration cohort. Cox regression results showed that using LAI antipsychotics for a longer duration was correlated with longer time to the first hospitalization for any cause and for schizophrenia. After multivariate regression, longer usage duration of LAI antipsychotics was associated with a decreased number of hospitalizations (-0.15 per year, P < 0.001), a decreased hospital length of stay (-1.50 days, P < 0.001), and reduced hospital payment (-26%, P < 0.001). Patients who are treated with LAI antipsychotics for a longer versus shorter duration use hospital resources less. PMID:24135840

  10. Strategic applications of long-acting acaricides against Rhipicephalus (Boophilus) microplus in northwestern Argentina, with an analysis of tick distribution among cattle.

    PubMed

    Nava, Santiago; Mangold, Atilio J; Canevari, José T; Guglielmone, Alberto A

    2015-03-15

    Strategic applications of long-acting acaricides for the control of Rhipicephalus (Boophilus) microplus in northwestern Argentina were evaluated for one year. In addition, tick distribution among cattle was analyzed to evaluate if partial selective treatment or culling the small proportion of most heavily infested animals were feasible options to control R. (B.) microplus. Two different treatments schemes based on two applications of fluazuron and one application of 3.15% ivermectin were performed. Treatments were made in late winter and spring so as to act on the small 1st spring generation of R. (B.) microplus, in order to preclude the rise of the larger autumn generation. The overall treatment effect was positively significant in both schemes. The number of ticks observed in the control group was significantly higher than in the treated groups on all post-treatment counts. Group 2 exhibited more than 80% of efficacy almost throughout the study period, whereas Group 1 exhibited an efficacy percentage higher than 80% in September, October, December, February, April and May, but not in November (73.4%), January (58.3%), March (45.2%) or June (53.4%). Absolute control was observed in Group 2 in the counts of September and October, and in Group 1 in the count of February. The control strategies evaluated in this work provide an acceptable control level with only three applications of acaricides; at the same time, they prevent the occurrence of the autumn peak of tick burdens, which is characteristic of R. (B.) microplus in northwestern Argentina. Tick distribution was markedly aggregated in all counts. Although ticks were not distributed evenly among calves, the individual composition of the most heavily infested group was not consistent throughout the study period. In addition, the level of aggregation varied with tick abundance. These results suggest that applying acaricides to a portion of the herd or culling the most infested individuals at a given moment of the

  11. [Preparation and the biological effect of fusion protein GLP-1-exendin-4/ IgG4(Fc) fusion protein as long acting GLP-1 receptor agonist].

    PubMed

    Zheng, Yun-cheng

    2015-12-01

    . It can be used as a long-acting GLP-1 agonists. PMID:27169293

  12. Mentoring, Task Sharing, and Community Outreach Through the TutoratPlus Approach: Increasing Use of Long-Acting Reversible Contraceptives in Senegal

    PubMed Central

    Gueye, Babacar; Wesson, Jennifer; Koumtingue, Djimadoum; Stratton, Sara; Viadro, Claire; Talla, Hawa; Dioh, Etienne; Cissé, Carol; Sebikali, Boniface; Mamadou Daff, Bocar

    2016-01-01

    ABSTRACT Background: To broaden access to family planning in rural areas and improve contraceptive prevalence, Senegal, in the context of wide method choice, is promoting implants and the intrauterine device, currently used throughout the country by only 5.6% of women of reproductive age who are in union, primarily urban women. Methods: The TutoratPlus performance improvement approach strengthens family planning clinical skills, particularly for long-acting reversible contraceptives (LARCs), through mentoring, task sharing, and community outreach. Following a 2013 baseline situation analysis, 290 participating facilities in 12 of Senegal's 14 regions developed action plans to address gaps identified in 3 areas: provider performance, equipment, and infrastructure. Between 2013 and 2014, 85 trained mentors coached, demonstrated skills, and observed 857 providers, including nurses, nonclinical family planning counselors, and community health workers (CHWs), in LARC service provision through two 5-day visits per facility at 21-day intervals. We used routine service delivery data and TutoratPlus mentoring data to assess changes in contraceptive use, including LARCs, 6 months before and 6 months after the mentoring intervention among 100 of the facilities with complete data. Results: The baseline assessment of 290 facilities found that fewer than half (47%) had a provider who could offer at least 1 LARC method, and 64% to 69% lacked kits. Post-intervention, all 290 facilities were adequately equipped and clinically able to offer LARCs. Among the 552 clinical providers, the percentage with acceptable LARC performance (at least 80% of observation checklist items correct) doubled from 32% to 67% over the 2 mentoring visits. In the 100 facilities with available comparison data, the number of new LARC users rose from 1,552 to 2,879 in the 6 months pre- and post-intervention—an 86% increase. Conclusion: Success of the TutoratPlus approach in Senegal is likely in part

  13. Effect of β2-adrenergic receptor gene (ADRB2) 3′ untranslated region polymorphisms on inhaled corticosteroid/long-acting β2-adrenergic agonist response

    PubMed Central

    2012-01-01

    Background Evidence suggests that variation in the length of the poly-C repeat in the 3′ untranslated region (3′UTR) of the β2-adrenergic receptor gene (ADRB2) may contribute to interindividual variation in β-agonist response. However, methodology in previous studies limited the assessment of the effect of sequence variation in the context of poly-C repeat length. The objectives of this study were to design a novel genotyping method to fully characterize sequence variation in the ADRB2 3′UTR poly-C repeat in asthma patients treated with inhaled corticosteroid and long-acting β2-adrenergic agonist (ICS/LABA) combination therapy, and to analyze the effect of the poly-C repeat polymorphism on clinical response. Methods In 2,250 asthma patients randomized to treatment with budesonide/formoterol or fluticasone/salmeterol in a six-month study (AstraZeneca study code: SD-039-0735), sequence diversity in the ADRB2 poly-C repeat region was determined using a novel sequencing-based genotyping method. The relationship between the poly-C repeat polymorphism and the incidence of severe asthma exacerbations, and changes in pulmonary function and asthma symptoms from baseline to the average during the treatment period, were analyzed. Results Poly-C repeat genotypes were assigned in 97% (2,192/2,250) of patients. Of the 13 different poly-C repeat alleles identified, six alleles occurred at a frequency of >5% in one or more population in this study. The repeat length of these six common alleles ranged from 10 to 14 nucleotides. Twelve poly-C repeat genotypes were observed at a frequency of >1%. No evidence of an association between poly-C repeat genotype and the incidence of severe asthma exacerbations was observed. Patients’ pulmonary function measurements improved and asthma symptoms declined when treated with ICS/LABA combination therapy regardless of poly-C repeat genotype. Conclusions The extensive sequence diversity present in the poly-C repeat region of the ADRB2

  14. Ampicillin Oral

    MedlinePlus

    ... capsule, liquid, and pediatric drops to take by mouth. It is usually taken every 6 hours (four ... blood thinners') such as warfarin (Coumadin), atenolol (Tenormin), oral contraceptives, probenecid (Benemid), rifampin, sulfasalazine, and vitamins.tell ...

  15. Oral pathology.

    PubMed

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  16. Oral Cancer

    MedlinePlus

    ... swallowing A lump in your neck An earache Oral cancer treatments may include surgery, radiation therapy or chemotherapy. Some patients have a combination of treatments. NIH: National Cancer Institute

  17. Oral Health

    MedlinePlus

    ... its box has the American Dental Association's (ADA) seal of acceptance, it is good for your oral ... dispensed solutions have the American Dental Association (ADA) seal. Other over-the-counter whitening products include whitening ...

  18. Oral Cancer

    MedlinePlus

    ... use. Some oral cancers are linked to human papilloma virus (HPV) infections of the mouth and throat. ... The number of oropharyngeal cancers linked to human papilloma virus (HPV) has risen dramatically over the past ...

  19. Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models.

    PubMed

    Kusumoto, Keiji; Igata, Hideki; Ojima, Mami; Tsuboi, Ayako; Imanishi, Mitsuaki; Yamaguchi, Fuminari; Sakamoto, Hiroki; Kuroita, Takanobu; Kawaguchi, Naohiro; Nishigaki, Nobuhiro; Nagaya, Hideaki

    2011-11-01

    The pharmacological profile of a novel angiotensin II type 1 receptor blocker, azilsartan medoxomil, was compared with that of the potent angiotensin II receptor blocker olmesartan medoxomil. Azilsartan, the active metabolite of azilsartan medoxomil, inhibited the binding of [(125)I]-Sar(1)-I1e(8)-angiotensin II to angiotensin II type 1 receptors. Azilsartan medoxomil inhibited angiotensin II-induced pressor responses in rats, and its inhibitory effects lasted 24h after oral administration. The inhibitory effects of olmesartan medoxomil disappeared within 24h. ID(50) values were 0.12 and 0.55 mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In conscious spontaneously hypertensive rats (SHRs), oral administration of 0.1-1mg/kg azilsartan medoxomil significantly reduced blood pressure at all doses even 24h after dosing. Oral administration of 0.1-3mg/kg olmesartan medoxomil also reduced blood pressure; however, only the two highest doses significantly reduced blood pressure 24h after dosing. ED(25) values were 0.41 and 1.3mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In renal hypertensive dogs, oral administration of 0.1-1mg/kg azilsartan medoxomil reduced blood pressure more potently and persistently than that of 0.3-3mg/kg olmesartan medoxomil. In a 2-week study in SHRs, azilsartan medoxomil showed more stable antihypertensive effects than olmesartan medoxomil and improved the glucose infusion rate, an indicator of insulin sensitivity, more potently (≥ 10 times) than olmesartan medoxomil. Azilsartan medoxomil also exerted more potent antiproteinuric effects than olmesartan medoxomil in Wistar fatty rats. These results suggest that azilsartan medoxomil is a potent angiotensin II receptor blocker that has an attractive pharmacological profile as an antihypertensive agent.

  20. Prevention of aspiration pneumonia (AP) with oral care.

    PubMed

    Tada, Akio; Miura, Hiroko

    2012-01-01

    AP is a major cause of morbidity and mortality in elderly patients, especially frail elderly patients. The aim of this article is to review effect of oral care, including oral hygiene and improvement of oral function, on the prevention of AP among elderly people in hospitals and nursing homes. There is now a substantial body of work studying the effect of oral care on the prevention of respiratory diseases. Oral hygiene, consisting of oral decontamination and mechanical cleaning by dental professionals, has resulted in significant clinical effects (decreased incidence of pneumonia and decreased mortality from respiratory diseases) in clinical randomized trials. Moreover, studies examining oral colonization by pneumonia pathogens have shown the effect of oral hygiene on eliminating these pathogens. In addition, swallowing training has been shown to improve the movement and function of swallowing-related muscles, also resulting in decreased incidence of pneumonia. These findings support the contention that oral care is effective in the prevention of AP.

  1. Oral biopsy: oral pathologist's perspective.

    PubMed

    Kumaraswamy, K L; Vidhya, M; Rao, Prasanna Kumar; Mukunda, Archana

    2012-01-01

    Many oral lesions may need to be diagnosed by removing a sample of tissue from the oral cavity. Biopsy is widely used in the medical field, but the practice is not quite widespread in dental practice. As oral pathologists, we have found many artifacts in the tissue specimen because of poor biopsy technique or handling, which has led to diagnostic pitfalls and misery to both the patient and the clinician. This article aims at alerting the clinicians about the clinical faults arising preoperatively, intraoperatively and postoperatively while dealing with oral biopsy that may affect the histological assessment of the tissue and, therefore, the diagnosis. It also reviews the different techniques, precautions and special considerations necessary for specific lesions.

  2. Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators

    PubMed Central

    van der Molen, T.; Postma, D. S.; Turner, M. O.; Jong, B. M.; Malo, J. L.; Chapman, K.; Grossman, R.; de Graaff, C. S.; Riemersma, R. A.; Sears, M. R.

    1997-01-01

    BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0

  3. Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model.

    PubMed Central

    Schally, A V; Kook, A I; Monje, E; Redding, T W; Paz-Bouza, J I

    1986-01-01

    The combination of hormonal treatment based on a long-acting delivery system for the agonist [6-D-tryptophan]luteinizing hormone-releasing hormone ([D-Trp6]-LH-RH) with the chemotherapeutic agent Novantrone (mitoxantrone dihydrochloride) was studied in the Dunning R3327H rat prostate cancer model. Microcapsules of [D-Trp6]-LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Novantrone (0.25 mg/kg) was injected intravenously once every 3 weeks. Three separate experiments were carried out. When the therapy was started 45 days after transplantation and continued for 70 days, tumor volume in the presence of the microcapsules (966 +/- 219 mm3) or Novantrone (3606 +/- 785 mm3) given alone was significantly decreased compared to controls (14,476 +/- 3045 mm3). However, the combination of microcapsules and Novantrone caused a greater inhibition of tumor growth (189 +/- 31 mm3) than the single agents. Similar effects were seen when the percent increase in tumor volume was examined. Tumor volume increased 10,527 +/- 1803% for the control group. The inhibition of growth caused by the [D-Trp6]LH-RH microcapsules alone (672 +/- 153% increase in volume) was again greater than that caused by Novantrone alone (2722 +/- 421% increase). The combination of the two agents was again the most effective, resulting in an increase in tumor volume of only 105 +/- 29%. Control tumors weighed 30.0 +/- 6.5 g. Tumor weights were much less in the groups treated with either microcapsules (3.28 +/- 0.69 g) or Novantrone (19.53 +/- 3.3 g) alone. The lowest tumor weights after 70 days of treatment were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and Novantrone (1.02 +/- 0.2 g). Testes and ventral prostate weights were significantly diminished by the administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Novantrone. In both of these

  4. Oral candidiasis.

    PubMed

    Millsop, Jillian W; Fazel, Nasim

    2016-01-01

    Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options.

  5. Myofibroblasts in oral lesions: A review

    PubMed Central

    Pinisetti, Soujanya; Manyam, Ravikanth; Suresh, Babburi; Aparna, V

    2014-01-01

    Myofibroblasts (MFs) are modified fibroblasts that express features of smooth muscle differentiation and were first observed in granulation tissue during wound healing. These cells play a key role in physiologic and pathologic processes like wound healing and tumorigenesis. The presence of MFs has been reported in normal oral tissues and pathologic conditions like reactive lesions, benign tumors, locally aggressive tumors and malignancies affecting the oral cavity. This article briefly reviews the important hallmarks related to the discovery, characterization and tissue distribution of MFs in oral health and disease. PMID:24959038

  6. Muscle strain (image)

    MedlinePlus

    A muscle strain is the stretching or tearing of muscle fibers. A muscle strain can be caused by sports, exercise, a ... something that is too heavy. Symptoms of a muscle strain include pain, tightness, swelling, tenderness, and the ...

  7. Oral Cancer

    MedlinePlus

    ... What are the effects of oral cancer on speech and swallowing? The effects of cancer on speech and swallowing depend on the location and size ... movement. This could result in unclear production of speech sounds made with the lips such as /p/, / ...

  8. Oral Warts

    MedlinePlus

    ... Title: Oral Warts Description: Warts are small, white, gray, or pinkish rough bumps that look like cauliflower. They can appear inside the lips and on other parts of the mouth. Credit: NIDCR publication: Mouth Problems + HIV Download: Low-Resolution Image High- ...

  9. Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia.

    PubMed

    Turncliff, Ryan; Hard, Marjie; Du, Yangchun; Risinger, Robert; Ehrich, Elliot W

    2014-11-01

    Aripiprazole lauroxil is a linker lipid ester of aripiprazole for extended-release intramuscular (IM) injection. This multicenter, randomized, open-label study evaluated the pharmacokinetics (PK), relative bioavailability, and tolerability of a single IM deltoid or gluteal injection of aripiprazole lauroxil in adult subjects with chronic stable schizophrenia or schizoaffective disorder. Forty-six subjects were randomized 1:1 to aripiprazole lauroxil 441 mg IM in the deltoid or gluteal muscle. Samples were collected through 89 days post-dose to measure levels of aripiprazole lauroxil, N-hydroxymethyl aripiprazole, aripiprazole, and dehydro-aripiprazole. Forty-three (93.5%) subjects completed all study assessments; most were CYP2D6 extensive or immediate metabolizers (96%); two (4%) were poor metabolizers. The PK of aripiprazole following aripiprazole lauroxil was characterized by a steady rise in plasma concentrations (Tmax 44-50 days), a broad peak, and prolonged exposure attributable to the dissolution of aripiprazole lauroxil and formation rate-limited elimination of aripiprazole (t1/2=15.4-19.2 days). Deltoid vs. gluteal administration resulted in slightly higher Cmax aripiprazole concentrations [1.31 (1.02, 1.67); GMR 90% CI]; total exposure (AUCinf) was similar between sites of administration [0.84 (0.57, 1.24)]. N-hydroxymethyl-aripiprazole and dehydro-aripiprazole exposures were 10% and 33-36%, respectively, of aripiprazole exposure following aripiprazole lauroxil. The most common adverse events were injection site pain in 20 subjects (43.5%) and headache in 6 subjects (13.0%) of mild intensity occurring at a similar rate with deltoid and gluteal administration. Exposure ranges with deltoid and gluteal administration overlapped, suggesting that these sites may be used interchangeably. Despite a higher incidence of adverse events, deltoid muscle provides a more accessible injection site and could facilitate patient acceptance.

  10. Accessory oral cavity

    PubMed Central

    Gnaneswaran, Manica Ramamoorthy; Varadarajan, Usha; Srinivasan, Ramesh; Kamatchi, Sangeetha

    2012-01-01

    This is a rare case report of a patient around 11 years with the complaint of extra mouth who reported to the hospital for removal of that extra mouth. On examination there was accessory oral cavity with small upper and lower lips, seven teeth and saliva was drooling out. Under general anesthesia crevicular incision from 32 to 43 was put and labial gingiva with alveolar mucosa was reflected completely and bone exposed to lower border of mandible. There were seven teeth resembling lower permanent anterior teeth in the accessory mouth, which was excised with the accessory lips. 41 extracted and osteotomy carried out extending the incision from the extracted site and osteotomy carried out. Dermoid cyst both below and above the mylohyoid muscle and rudimentary tongue found and excised and the specimen sent for histopathological examination. The wound was closed and uneventful healing noted to the satisfaction of the patient. This is a rare and interesting case which has been documented. PMID:23833508

  11. Oral care.

    PubMed

    Hitz Lindenmüller, Irène; Lambrecht, J Thomas

    2011-01-01

    Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable. PMID:21325845

  12. Oral care.

    PubMed

    Hitz Lindenmüller, Irène; Lambrecht, J Thomas

    2011-01-01

    Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable.

  13. Oral Cancer Screening

    MedlinePlus

    ... Prevention Oral Cavity and Oropharyngeal Cancer Screening Research Oral Cavity and Oropharyngeal Cancer Screening (PDQ®)–Patient Version What ... These are called diagnostic tests . General Information About Oral Cavity and Oropharyngeal Cancer Key Points Oral cavity and ...

  14. Stromal myofibroblasts in oral leukoplakia and oral squamous cell carcinoma

    PubMed Central

    de-Assis, Eliene M.; Pimenta, Luiz G.G.S.; Costa-e-Silva, Edson; Souza, Paulo E.A.

    2012-01-01

    Objectives: Oral leukoplakia (OL) is the main potentially malignant disorder and oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Stromal myofibroblasts play an important role in tumor invasion and metastasis, due to its ability to modify the extracellular matrix. This study aimed to evaluate the presence of stromal myofibroblasts in OL and OSCC. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between histologically high- and low-invasive OSCC were also assessed. Study Design: A total of 30 OL and 41 OSCC from archival formalin-fixed, paraffin-embedded specimens were evaluated. 10 samples of normal oral mucosa were used as a control. Myofibroblasts were identified by immunohistochemical detection of alpha smooth muscle actin and its presence was classified as negative, scanty or abundant. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between high- and low-invasive OSCC were analyzed using the Mann-Whitney test. Results: Myofibroblasts were not detected in normal oral mucosa and OL, whatever its histological grade. In OSCC, the presence of stromal myofibroblasts was classified as negative in 11 (26.8%), scanty in 15 (36.6%), and abundant in 15 samples (36.6%). The presence of stromal myofibroblasts was statistically higher in high-invasive OSCC than in low-invasive OSCC (p<0.05). Conclusions: Stromal myofibroblasts were not detected in OL, indicating that these cells are not important during oral carcinogenesis. Nevertheless, stromal myofibroblasts were heterogeneously detected in OSCC and its presence was higher in tumors with a more diffuse histological pattern of invasion. These findings suggest that myofibroblasts are associated with the creation of a permissive environment for tumor invasion in OSCC. Key words:Leukoplakia, oral squamous cell carcinoma, myofibroblast. PMID:22322518

  15. Capillary muscle

    PubMed Central

    Cohen, Caroline; Mouterde, Timothée; Quéré, David; Clanet, Christophe

    2015-01-01

    The contraction of a muscle generates a force that decreases when increasing the contraction velocity. This “hyperbolic” force–velocity relationship has been known since the seminal work of A. V. Hill in 1938 [Hill AV (1938) Proc R Soc Lond B Biol Sci 126(843):136–195]. Hill’s heuristic equation is still used, and the sliding-filament theory for the sarcomere [Huxley H, Hanson J (1954) Nature 173(4412):973–976; Huxley AF, Niedergerke R (1954) Nature 173(4412):971–973] suggested how its different parameters can be related to the molecular origin of the force generator [Huxley AF (1957) Prog Biophys Biophys Chem 7:255–318; Deshcherevskiĭ VI (1968) Biofizika 13(5):928–935]. Here, we develop a capillary analog of the sarcomere obeying Hill’s equation and discuss its analogy with muscles. PMID:25944938

  16. Strategies to Reduce the Tampering and Subsequent Abuse of Long-acting Opioids: Potential Risks and Benefits of Formulations With Physical or Pharmacologic Deterrents to Tampering

    PubMed Central

    Stanos, Steven P.; Bruckenthal, Patricia; Barkin, Robert L.

    2012-01-01

    Increased prescribing of opioid analgesics for chronic noncancer pain may reflect acceptance that opioid benefits outweigh risks of adverse events for a broadening array of indications and patient populations; however, a parallel increase in the abuse, misuse, and diversion of prescription opioids has resulted. There is an urgent need to reduce opioid tampering and subsequent abuse without creating barriers to safe, effective analgesia. Similar to the “magic bullet” concept of antibiotic development (kill the bacteria without harming the patient), the idea behind reformulating opioid analgesics is to make them more difficult to tamper with and abuse by drug abusers but innocuous to the compliant patient. As antibiotics exploit differences in bacterial and human physiology, tamper-resistant formulations depend on differences in the way drug abusers and compliant patients consume opioids. Most opioid abusers tamper with tablets to facilitate oral, intranasal, or intravenous administration, whereas compliant patients usually take intact tablets. Pharmaceutical strategies to deter opioid abuse predominantly focus on tablet tampering, incorporating physical barriers (eg, crush resistance) or embedded chemicals that render tampered tablets inert, unusable, or noxious. Deterring tampering and abuse of intact tablets is more challenging. At present, only a few formulations with characteristics designed to oppose tampering for abuse have received approval by the US Food and Drug Administration, and none has been permitted to include claims of abuse deterrence or tamper resistance in their labeling. This review discusses the potential benefits, risks, and limitations associated with available tamper-resistant opioids and those in development. PMID:22766088

  17. Topographic probes of angiotensin and receptor: potent angiotensin II agonist containing diphenylalanine and long-acting antagonists containing biphenylalanine and 2-indan amino acid in position 8.

    PubMed

    Hsieh, K H; LaHann, T R; Speth, R C

    1989-04-01

    A series of phenylalanine-mimicking amino acids with increasing conformational restraint were prepared and incorporated into angiotensin II, in order to develop topographic probes of angiotensin useful for probing receptor boundaries by molecular graphics analysis and for conformational analysis of the ligand by NMR. In binding studies, all analogues displayed high affinity for rat uterus (Ki of 0.74-6.08 nM) and brain (0.46-1.82 nM) receptors. In smooth muscle (rat uterus) contraction assay, the diphenylalanine-containing [Sar1,Dip8]AII and [Sar1,D-Dip8]AII were potent agonists with respectively 284% and 48% activity of [Asn1]AII. In contrast, the biphenylalanine-containing [Sar1,Bip8]AII, [Sar1,D-Bip8]AII, and the 2-indan amino acid containing [Sar1,2-Ind8]AII were potent inhibitors, approximately 9, 2, and 1.4 times more effective than a standard antagonist, [Sar1,Leu8]AII. Their respective pA10 values in rat uterus assay were 8.87, 8.70, and 8.82. By comparison, the pA10 value for [Sar1,Leu8]AII was 8.35. In rats, a single dose of 10 micrograms of [Sar1,2-Ind8]AII or [Sar1,Bip8]AII produced prolonged blockade of the pressor response toward angiotensin II for over 90 min. The very different pharmacological profiles of these rigid aromatic analogues suggest that the angiotensin receptor activation site consists of a relatively wide and elongated pocket with a narrow opening.

  18. Cytokine-Induced Loss of Glucocorticoid Function: Effect of Kinase Inhibitors, Long-Acting β2-Adrenoceptor Agonist and Glucocorticoid Receptor Ligands

    PubMed Central

    Rider, Christopher F.; Shah, Suharsh; Miller-Larsson, Anna; Giembycz, Mark A.; Newton, Robert

    2015-01-01

    Acting on the glucocorticoid receptor (NR3C1), glucocorticoids are widely used to treat inflammatory diseases. However, glucocorticoid resistance often leads to suboptimal asthma control. Since glucocorticoid-induced gene expression contributes to glucocorticoid activity, the aim of this study was to use a 2×glucocorticoid response element (GRE) reporter and glucocorticoid-induced gene expression to investigate approaches to combat cytokine-induced glucocorticoid resistance. Pre-treatment with tumor necrosis factor-α (TNF) or interleukin-1β inhibited dexamethasone-induced mRNA expression of the putative anti-inflammatory genes RGS2 and TSC22D3, or just TSC22D3, in primary human airway epithelial and smooth muscle cells, respectively. Dexamethasone-induced DUSP1 mRNA was unaffected. In human bronchial epithelial BEAS-2B cells, dexamethasone-induced TSC22D3 and CDKN1C expression (at 6 h) was reduced by TNF pre-treatment, whereas DUSP1 and RGS2 mRNAs were unaffected. TNF pre-treatment also reduced dexamethasone-dependent 2×GRE reporter activation. This was partially reversed by PS-1145 and c-jun N-terminal kinase (JNK) inhibitor VIII, inhibitors of IKK2 and JNK, respectively. However, neither inhibitor affected TNF-dependent loss of dexamethasone-induced CDKN1C or TSC22D3 mRNA. Similarly, inhibitors of the extracellular signal-regulated kinase, p38, phosphoinositide 3-kinase or protein kinase C pathways failed to attenuate TNF-dependent repression of the 2×GRE reporter. Fluticasone furoate, fluticasone propionate and budesonide were full agonists relative to dexamethasone, while GSK9027, RU24858, des-ciclesonide and GW870086X were partial agonists on the 2×GRE reporter. TNF reduced reporter activity in proportion with agonist efficacy. Full and partial agonists showed various degrees of agonism on RGS2 and TSC22D3 expression, but were equally effective at inducing CDKN1C and DUSP1, and did not affect the repression of CDKN1C or TSC22D3 expression by TNF. Finally

  19. Restricted mouth opening and trismus in oral oncology.

    PubMed

    Satheeshkumar, P S; Mohan, Minu P; Jacob, Jayan

    2014-06-01

    Restricted mouth opening (RMO) and trismus are terms commonly used in oral oncology in instances where there is difficulty in mouth opening. The term trismus in oral oncology is mainly used to indicate the radiation-induced fibrosis of the muscles of mastication. The treatment given for RMO as reported in the literature is given for muscular dysfunction trismus, whereas RMO in oral oncology can occur owing to various reasons other than muscular dysfunction. RMO occurs in various conditions of the oral cavity; in posterior pharyngeal infection, where it is termed reflectory trismus; in oral submucous fibrosis; in oral mucosal disorders; in the use of certain drugs; and in minor dental procedures of the posterior oral cavity. The usage of the term trismus in all RMO cases would complicate the treatment; thus, the word should not be used in all RMO cases.

  20. Selection of Rilpivirine-Resistant HIV-1 in a Seroconverter From the SSAT 040 Trial Who Received the 300-mg Dose of Long-Acting Rilpivirine (TMC278LA).

    PubMed

    Penrose, Kerri J; Parikh, Urvi M; Hamanishi, Kristen A; Else, Laura; Back, David; Boffito, Marta; Jackson, Akil; Mellors, John W

    2016-03-15

    The injectable long-acting formulation of rilpivirine (TMC278LA) is a promising preexposure prophylaxis (PrEP) candidate for prevention of human immunodeficiency virus type 1 (HIV-1) infection. We evaluated HIV-1 in plasma obtained from an unexpected seroconverter in the 300-mg arm of the SSAT040 TMC278LA pharmacokinetic study for rilpivirine (RPV) resistance. Infection with wild-type HIV-1 was confirmed on day 84 after TMC278LA injection, and the K101E mutation was detected on day 115. Plasma-derived HIV-1 clones containing K101E had 4-fold increased resistance to RPV and 4-8-fold increased cross-resistance to etravirine, nevirapine, and efavirenz compared with wild type HIV-1 plasma-derived clones from the same individual. This case is a unique instance of infection with wild-type HIV-1 and subsequent selection of resistant virus by persistent exposure to long-acting PrEP. PMID:26563240

  1. Oral leiomyosarcoma in a woodchuck (Marmota monax).

    PubMed

    Kang, Byeong-Cheol; Jang, Dong-Deuk; Lee, Sang-Koo

    2005-03-01

    We report the case of a 4-year-old female woodchuck (Marmota monax) which presented with a white, firm and discrete mass in the hard palate. The mass extended into the oral cavity but it was well separated from the surrounding tissues. Histology of the tumor showed a malignant mesenchymal tumor with pleomorphic spindle cells varying in degrees of differentiation and density. The neoplastic cells had moderate amounts of granular or fibrillar eosinophilic cytoplasm with indistinct cell margins. Nuclei were oval to elongated and frequently blunt-ended with vesicular chromatin. Immunohistochemical study showed that the neoplastic cells expressed vimentin and alpha-smooth muscle actin but did not express desmin, pan-cytokeratin, and S-100. Therefore, histology and immunohistochemistry revealed that the tumor was oral leiomyosarcoma. Oral cavity is an extremely rare site for leiomyosarcoma and the present case is the first report of spontaneous oral leiomyosarcoma in animals.

  2. Muscle strain treatment

    MedlinePlus

    Treatment - muscle strain ... Question: How do you treat a muscle strain ? Answer: Rest the strained muscle and apply ice for the first few days after the injury. Anti-inflammatory medicines or acetaminophen ( ...

  3. Eye muscle repair - discharge

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000111.htm Eye muscle repair - discharge To use the sharing features on ... enable JavaScript. You or your child had eye muscle repair surgery to correct eye muscle problems that ...

  4. [Dynamic rehabilitation in facial paralysis with the surgical flap and temporalis muscle transposition without muscle lengthening: review and case report].

    PubMed

    Shipkov, Kh; Anastasov, Iu

    2005-01-01

    There are various surgical procedures for the reanimation of patients with long-standing facial paralysis. Temporalis muscle transfer is reliable for the reanimation of long-standing facial paralysis often employed when facial nerve reinnervation. It can be used as well for the immediate treatment of complete facial paralysis (more than 1 year) because temporalis muscle transposition does not interfere with neuronal regeneration. During the last few years the techniques employing the tendon of the temporalis muscle for the rehabilitation of the oral commissure gain increasing importance. The authors analyse the different options for reanimation after facial paralysis and report on a case of facial reanimation via temporalis muscle transfer.

  5. [Oral pain].

    PubMed

    Benslama, Lotfi

    2002-02-15

    Pain, a major symptom of stomatological disease, usually leads to a specialist consultation. Most commonly it is caused by dental caries and differs in nature and in intensity according to the stage of disease: dentinitis, pulpitis, desmodontitis and dental abscess. Added to this is peridental pain and the pre- and post-operative pains related to these diseases. Almost all oral-maxillary pathology is painful, be it boney such as in osteomyelitis and fractures, mucosal in gingivo-stomatitis and aphthous ulcers, or tumourous. However, besides the "multidisciplinary" facial pains such as facial neuralgia and vascular pain, two pain syndromes are specific to stomatology: pain of the tempero-mandibular joint associated with problems of the bite and glossodynia, a very common somatic expression of psychological problems.

  6. [Oral contraception].

    PubMed

    Guillat, J C

    1980-04-20

    OC (oral contraception) includes the combined and sequential methods, postcoital and progestin only contraception, mini pills, and macro pills. The mechanism of action of OC modifies the hypothalamo-hypophysary secretion, the uterine mucosa, and the cervical mucus. Effectiveness of OC is nearly 100%; prescription of OC requires a complete clinical and biological evaluation of the patient. Contraindications to OC are any form of cancer, hypertension, vascular or thrombotic antecedents, obesity, tabagism, diabetes. OC users must be checked at least every 6 months, and treatment can last, if there are no evident signs of side effects, until about age 40. The most commonly known side effects of OC are menstruation disorders, cardio- and cerebrovascular effects, hepatic and metabolic effects; there is no evidence that OC can cause carcinogenic effects, but it can increase teratogenic risk. The association of OC with such drugs as Rifampicine, anticonvulsants and/or tranquillizers, can nullify contraceptive effectiveness. PMID:6900393

  7. Muscle shape consistency and muscle volume prediction of thigh muscles.

    PubMed

    Mersmann, F; Bohm, S; Schroll, A; Boeth, H; Duda, G; Arampatzis, A

    2015-04-01

    The present study investigated the applicability of a muscle volume prediction method using only the muscle length (L(M)), the maximum anatomical cross-sectional area (ACSA(max)), and a muscle-specific shape factor (p) on the quadriceps vastii. L(M), ACSA(max), muscle volume, and p were obtained from magnetic resonance images of the vastus intermedius (VI), lateralis (VL), and medialis (VM) of female (n = 20) and male (n = 17) volleyball athletes. The average p was used to predict muscle volumes (V(p)) using the equation V(p)  = p × ACSA(max)  × L(M). Although there were significant differences in the muscle dimensions between male and female athletes, p was similar and on average 0.582, 0.658, 0.543 for the VI, VL, and VM, respectively. The position of ACSA(max) showed low variability and was at 57%, 60%, and 81% of the thigh length for VI, VL, and VM. Further, there were no significant differences between measured and predicted muscle volumes with root mean square differences of 5-8%. These results suggest that the muscle shape of the quadriceps vastii is independent of muscle dimensions or sex and that the prediction method could be sensitive enough to detect changes in muscle volume related to degeneration, atrophy, or hypertrophy.

  8. Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle.

    PubMed

    Giannesini, Benoît; Le Fur, Yann; Cozzone, Patrick J; Verleye, Marc; Le Guern, Marie-Emmanuelle; Bendahan, David

    2011-09-30

    Citrulline malate (CM; CAS 54940-97-5, Stimol®) is known to limit the deleterious effect of asthenic state on muscle function, but its effect under healthy condition remains poorly documented. The aim of this longitudinal double-blind study was to investigate the effect of oral ingestion of CM on muscle mechanical performance and bioenergetics in normal rat. Gastrocnemius muscle function was investigated strictly non-invasively using nuclear magnetic resonance techniques. A standardized rest-stimulation- (5.7 min of repeated isometric contractions electrically induced by transcutaneous stimulation at a frequency of 3.3 Hz) recovery-protocol was performed twice, i.e., before (t(0)-24 h) and after (t(0)+48 h) CM (3 g/kg/day) or vehicle treatment. CM supplementation did not affect PCr/ATP ratio, [PCr], [Pi], [ATP] and intracellular pH at rest. During the stimulation period, it lead to a 23% enhancement of specific force production that was associated to significant decrease in both PCr (28%) and oxidative (32%) costs of contraction, but had no effect on the time-courses of phosphorylated compounds and intracellular pH. Furthermore, both the rate of PCr resynthesis during the post-stimulation period (VPCr(rec)) and the oxidative ATP synthesis capacity (Q(max)) remained unaffected by CM treatment. These data demonstrate that CM supplementation under healthy condition has an ergogenic effect associated to an improvement of muscular contraction efficiency. PMID:21664351

  9. CARDIAC MUSCLE

    PubMed Central

    Sommer, Joachim R.; Johnson, Edward A.

    1968-01-01

    With light and electron microscopy a comparison has been made of the morphology of ventricular (V) and Purkinje (P) fibers of the hearts of guinea pig, rabbit, cat, dog, goat, and sheep. The criteria, previously established for the rabbit heart, that V fibers are distinguished from P fibers by the respective presence and absence of transverse tubules is shown to be true for all animals studied. No evidence was found of a permanent connection between the sarcoplasmic reticulum and the extracellular space. The sarcoplasmic reticulum (SR) of V fibers formed couplings with the sarcolemma of a transverse tubule (interior coupling) and with the peripheral sarcolemma (peripheral coupling), whereas in P fibers the SR formed only peripheral couplings. The forms of the couplings were identical. The significance, with respect to excitation-contraction coupling, of the difference in the form of the couplings in cardiac versus skeletal muscle is discussed together with the electrophysiological implications of the differing geometries of bundles of P fibers from different animals. PMID:5645545

  10. Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(-/-) Collies after oral administration

    PubMed Central

    2014-01-01

    Background Fluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. This study investigated the safety of oral administration of fluralaner at 3 times the highest expected clinical dose to Multi Drug Resistance Protein 1 (MDR1(-/-)) gene defect Collies. Methods Sixteen Collies homozygous for the MDR1 deletion mutation were included in the study. Eight Collies received fluralaner chewable tablets once at a dose of 168 mg/kg; eight sham dosed Collies served as controls. All Collies were clinically observed until 28 days following treatment. Results No adverse events were observed subsequent to fluralaner treatment of MDR1(-/-) Collies at three times the highest expected clinical dose. Conclusions Fluralaner chewable tablets are well tolerated in MDR1(-/-) Collies following oral administration. PMID:24602342

  11. An anatomical commentary on the concept of infantile oral sadism.

    PubMed

    Freeman, R; Freeman, T

    1992-01-01

    Although this paper is entitled 'An anatomical commentary on the concept of infantile oral sadism' it is also an attempt to examine hypotheses regarding the sources of oral sadism. Freud did not explicitly refer to an oral sadistic phase of development in early infancy, believing as he did that sadism was a component instinct. Abraham postulated that oral sadism arises when the teeth erupt and the jaw muscles function. Melanie Klein, however, came to claim that oral sadistic impulses operate from birth and arise from the infant's innate potential for fantasy. This hypothesis is akin to Freud's theory of primal fantasies. The anatomical record supports Abraham's theory of the source of oral sadism. PMID:1512124

  12. Embryonal rhabdomyosarcoma: A rare oral tumor

    PubMed Central

    Datta, Sila; Ray, Jay Gopal; Deb, Tushar; Patsa, Santanu

    2016-01-01

    Rhabdomyosarcoma is the malignant neoplasm of striated muscle and a relatively uncommon tumor of the oral cavity. Embryonal variety is the most common subtype, observed in children below 10 years of age but occasionally seen in adolescents and young adults. The present report describes a case of embryonal rhabdomyosarcoma in the left posterior buccal mucosa, with extension in the adjacent alveolus, soft palate, oropharynx and nasopharynx of a 17-year-old female. PMID:27721622

  13. Exercise in muscle glycogen storage diseases.

    PubMed

    Preisler, Nicolai; Haller, Ronald G; Vissing, John

    2015-05-01

    Glycogen storage diseases (GSD) are inborn errors of glycogen or glucose metabolism. In the GSDs that affect muscle, the consequence of a block in skeletal muscle glycogen breakdown or glucose use, is an impairment of muscular performance and exercise intolerance, owing to 1) an increase in glycogen storage that disrupts contractile function and/or 2) a reduced substrate turnover below the block, which inhibits skeletal muscle ATP production. Immobility is associated with metabolic alterations in muscle leading to an increased dependence on glycogen use and a reduced capacity for fatty acid oxidation. Such changes may be detrimental for persons with GSD from a metabolic perspective. However, exercise may alter skeletal muscle substrate metabolism in ways that are beneficial for patients with GSD, such as improving exercise tolerance and increasing fatty acid oxidation. In addition, a regular exercise program has the potential to improve general health and fitness and improve quality of life, if executed properly. In this review, we describe skeletal muscle substrate use during exercise in GSDs, and how blocks in metabolic pathways affect exercise tolerance in GSDs. We review the studies that have examined the effect of regular exercise training in different types of GSD. Finally, we consider how oral substrate supplementation can improve exercise tolerance and we discuss the precautions that apply to persons with GSD that engage in exercise.

  14. Dynamic role of myofibroblasts in oral lesions

    PubMed Central

    Bagul, Neeta; Ganjre, Anjali; Goryawala, SN; Kathariya, Rahul; Dusane, Shrikant

    2015-01-01

    Fibroblasts are the most abundant cellular components of connective tissue. They possess phenotypical heterogenicity and may be present in the form of smooth muscle cells or myofibroblasts (MFs). MFs are spindle-shaped cells with stress fibres and well-developed fibronexus, and they display α-smooth muscle actin immunohistochemically and smooth-muscle myofilaments ultrastructurally. MFs play a crucial role in physiological and pathological processes. Derived from various sources, they play pivotal roles not only by synthesizing and producing extracellular matrix components, such as other connective tissue cells, but also are involved in force production. In the tissue remodelling phase of wound closure, integrin-mediated interactions between MFs and type I collagen result in scar tissue formation. The tumour stroma in oral cancer actively recruits various cell types into the tumour mass, where they act as different sources of MFs. This article reviews the importance of MFs and its role in pathological processes such as wound healing, odontogenic cysts and tumours, salivary gland tumours, oral preneoplasia, and oral squamous cell carcinoma. Research oriented on blocking the transdifferentiation of fibroblasts into MFs can facilitate the development of noninvasive therapeutic strategies for the treatment of fibrosis and/or cancer. PMID:26677439

  15. Oral Health in Pregnancy.

    PubMed

    Hartnett, Erin; Haber, Judith; Krainovich-Miller, Barbara; Bella, Abigail; Vasilyeva, Anna; Lange Kessler, Julia

    2016-01-01

    Oral health is crucial to overall health. Because of normal physiologic changes, pregnancy is a time of particular vulnerability in terms of oral health. Pregnant women and their providers need more knowledge about the many changes that occur in the oral cavity during pregnancy. In this article we describe the importance of the recognition, prevention, and treatment of oral health problems in pregnant women. We offer educational strategies that integrate interprofessional oral health competencies. PMID:27281467

  16. Unusual fibularis (peroneus) muscle.

    PubMed

    Fabrizio, Philip A

    2015-10-01

    Routine dissection has identified a previously unrecorded fibularis (peroneus) muscle in a 74-year-old male cadaver. The anomalous fibularis muscle was found lying immediately antero-medial to the fibularis longus (FL) muscle of the left leg. The anomalous muscle arose from the muscle belly of the FL in the proximal 1/2 of the leg. The muscle belly gave way to a long slender tendon that continued distally behind the lateral malleolus and inserted onto the superficial aspect of the inferior fibular retinaculum. The current finding and clinical significance are discussed.

  17. Human Muscle Fiber

    NASA Technical Reports Server (NTRS)

    2003-01-01

    The stimulus of gravity affects RNA production, which helps maintain the strength of human muscles on Earth (top), as seen in this section of muscle fiber taken from an astronaut before spaceflight. Astronauts in orbit and patients on Earth fighting muscle-wasting diseases need countermeasures to prevent muscle atrophy, indicated here with white lipid droplets (bottom) in the muscle sample taken from the same astronaut after spaceflight. Kerneth Baldwin of the University of California, Irvine, is conducting research on how reducing the stimulus of gravity affects production of the RNA that the body uses as a blueprint for making muscle proteins. Muscle proteins are what give muscles their strength, so when the RNA blueprints aren't available for producing new proteins to replace old ones -- a situation that occurs in microgravity -- the muscles atrophy. When the skeletal muscle system is exposed to microgravity during spaceflight, the muscles undergo a reduced mass that translates to a reduction in strength. When this happens, muscle endurance decreases and the muscles are more prone to injury, so individuals could have problems in performing extravehicular activity [space walks] or emergency egress because their bodies are functionally compromised.

  18. Muscle strain injuries.

    PubMed

    Garrett, W E

    1996-01-01

    One of the most common injuries seen in the office of the practicing physician is the muscle strain. Until recently, little data were available on the basic science and clinical application of this basic science for the treatment and prevention of muscle strains. Studies in the last 10 years represent action taken on the direction of investigation into muscle strain injuries from the laboratory and clinical fronts. Findings from the laboratory indicate that certain muscles are susceptible to strain injury (muscles that cross multiple joints or have complex architecture). These muscles have a strain threshold for both passive and active injury. Strain injury is not the result of muscle contraction alone, rather, strains are the result of excessive stretch or stretch while the muscle is being activated. When the muscle tears, the damage is localized very near the muscle-tendon junction. After injury, the muscle is weaker and at risk for further injury. The force output of the muscle returns over the following days as the muscle undertakes a predictable progression toward tissue healing. Current imaging studies have been used clinically to document the site of injury to the muscle-tendon junction. The commonly injured muscles have been described and include the hamstring, the rectus femoris, gastrocnemius, and adductor longus muscles. Injuries inconsistent with involvement of a single muscle-tendon junction proved to be at tendinous origins rather than within the muscle belly. Important information has also been provided regarding injuries with poor prognosis, which are potentially repairable surgically, including injuries to the rectus femoris muscle, the hamstring origin, and the abdominal wall. Data important to the management of common muscle injuries have been published. The risks of reinjury have been documented. The early efficacy and potential for long-term risks of nonsteroidal antiinflammatory agents have been shown. New data can also be applied to the field

  19. [Oral viral infections].

    PubMed

    Parent, Dominique

    2016-02-01

    Exclude herpes infection in the presence of acute oral ulcers of unknown origin, particularly in patients in poor general condition. Remember that asymptomatic HSV-1 shedding in saliva may result in an oral-genital transmission. Perform an anogenital examination and a screening for other sexually transmitted diseases when oral warts are diagnosed. Search for immunosuppression and monitor the patient (screening for a potential associated carcinoma) when there is rapid growth of oral warts. Consider all the clinical signs (systemic, skin, other mucosa, immunity...) when a patient has an enanthem or oral ulcerations. Ask for a HIV test when an oral Kaposi's sarcoma, a hairy leukoplakia or major aphthae are diagnosed. PMID:26854091

  20. Healthy Muscles Matter

    MedlinePlus

    ... keep my muscles more healthy? Definitions What can go wrong? Injuries Almost everyone has had sore muscles ... If you have been inactive, “start low and go slow” by gradually increasing how often and how ...

  1. Eye muscle repair - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100062.htm Eye muscle repair - series—Normal anatomy To use the sharing ... the eyeball to the eye socket. The external muscles of the eye are found behind the conjunctiva. ...

  2. The Effects of Creatine Supplementation on Exercise-Induced Muscle Damage.

    ERIC Educational Resources Information Center

    Rawson, Eric S.; Gunn, Bridget; Clarkson, Priscilla M.

    2001-01-01

    Investigated the effects of oral creatine (Cr) supplementation on markers of exercise-induced muscle damage following high-force eccentric exercise in men randomly administered Cr or placebo. Results indicated that 5 days of Cr supplementation did not reduce indirect makers of muscle damage or enhance recovery from high-force eccentric exercise.…

  3. Rapid Contraceptive Uptake and Changing Method Mix With High Use of Long-Acting Reversible Contraceptives in Crisis-Affected Populations in Chad and the Democratic Republic of the Congo.

    PubMed

    Rattan, Jesse; Noznesky, Elizabeth; Curry, Dora Ward; Galavotti, Christine; Hwang, Shuyuan; Rodriguez, Mariela

    2016-08-11

    The global health community has recognized that expanding the contraceptive method mix is a programmatic imperative since (1) one-third of unintended pregnancies are due to method failure or discontinuation, and (2) the addition of a new method to the existing mix tends to increase total contraceptive use. Since July 2011, CARE has been implementing the Supporting Access to Family Planning and Post-Abortion Care (SAFPAC) initiative to increase the availability, quality, and use of contraception, with a particular focus on highly effective and long-acting reversible methods-intrauterine devices (IUDs) and implants-in crisis-affected settings in Chad and the Democratic Republic of the Congo (DRC). This initiative supports government health systems at primary and referral levels to provide a wide range of contraceptive services to people affected by conflict and/or displacement. Before the initiative, long-acting reversible methods were either unknown or unavailable in the intervention areas. However, as soon as trained providers were in place, we noted a dramatic and sustained increase in new users of all contraceptive methods, especially implants, with total new clients reaching 82,855, or 32% of the estimated number of women of reproductive age in the respective catchment areas in both countries, at the end of the fourth year. Demand for implants was very strong in the first 6 months after provider training. During this time, implants consistently accounted for more than 50% of the method mix, reaching as high as 89% in Chad and 74% in DRC. To ensure that all clients were getting the contraceptive method of their choice, we conducted a series of discussions and sought feedback from different stakeholders in order to modify program strategies. Key program modifications included more focused communication in mass media, community, and interpersonal channels about the benefits of IUDs while reinforcing the wide range of methods available and refresher training for

  4. Rapid Contraceptive Uptake and Changing Method Mix With High Use of Long-Acting Reversible Contraceptives in Crisis-Affected Populations in Chad and the Democratic Republic of the Congo.

    PubMed

    Rattan, Jesse; Noznesky, Elizabeth; Curry, Dora Ward; Galavotti, Christine; Hwang, Shuyuan; Rodriguez, Mariela

    2016-08-11

    The global health community has recognized that expanding the contraceptive method mix is a programmatic imperative since (1) one-third of unintended pregnancies are due to method failure or discontinuation, and (2) the addition of a new method to the existing mix tends to increase total contraceptive use. Since July 2011, CARE has been implementing the Supporting Access to Family Planning and Post-Abortion Care (SAFPAC) initiative to increase the availability, quality, and use of contraception, with a particular focus on highly effective and long-acting reversible methods-intrauterine devices (IUDs) and implants-in crisis-affected settings in Chad and the Democratic Republic of the Congo (DRC). This initiative supports government health systems at primary and referral levels to provide a wide range of contraceptive services to people affected by conflict and/or displacement. Before the initiative, long-acting reversible methods were either unknown or unavailable in the intervention areas. However, as soon as trained providers were in place, we noted a dramatic and sustained increase in new users of all contraceptive methods, especially implants, with total new clients reaching 82,855, or 32% of the estimated number of women of reproductive age in the respective catchment areas in both countries, at the end of the fourth year. Demand for implants was very strong in the first 6 months after provider training. During this time, implants consistently accounted for more than 50% of the method mix, reaching as high as 89% in Chad and 74% in DRC. To ensure that all clients were getting the contraceptive method of their choice, we conducted a series of discussions and sought feedback from different stakeholders in order to modify program strategies. Key program modifications included more focused communication in mass media, community, and interpersonal channels about the benefits of IUDs while reinforcing the wide range of methods available and refresher training for

  5. Rapid Contraceptive Uptake and Changing Method Mix With High Use of Long-Acting Reversible Contraceptives in Crisis-Affected Populations in Chad and the Democratic Republic of the Congo

    PubMed Central

    Rattan, Jesse; Noznesky, Elizabeth; Curry, Dora Ward; Galavotti, Christine; Hwang, Shuyuan; Rodriguez, Mariela

    2016-01-01

    ABSTRACT The global health community has recognized that expanding the contraceptive method mix is a programmatic imperative since (1) one-third of unintended pregnancies are due to method failure or discontinuation, and (2) the addition of a new method to the existing mix tends to increase total contraceptive use. Since July 2011, CARE has been implementing the Supporting Access to Family Planning and Post-Abortion Care (SAFPAC) initiative to increase the availability, quality, and use of contraception, with a particular focus on highly effective and long-acting reversible methods—intrauterine devices (IUDs) and implants—in crisis-affected settings in Chad and the Democratic Republic of the Congo (DRC). This initiative supports government health systems at primary and referral levels to provide a wide range of contraceptive services to people affected by conflict and/or displacement. Before the initiative, long-acting reversible methods were either unknown or unavailable in the intervention areas. However, as soon as trained providers were in place, we noted a dramatic and sustained increase in new users of all contraceptive methods, especially implants, with total new clients reaching 82,855, or 32% of the estimated number of women of reproductive age in the respective catchment areas in both countries, at the end of the fourth year. Demand for implants was very strong in the first 6 months after provider training. During this time, implants consistently accounted for more than 50% of the method mix, reaching as high as 89% in Chad and 74% in DRC. To ensure that all clients were getting the contraceptive method of their choice, we conducted a series of discussions and sought feedback from different stakeholders in order to modify program strategies. Key program modifications included more focused communication in mass media, community, and interpersonal channels about the benefits of IUDs while reinforcing the wide range of methods available and refresher

  6. Exercising with a Muscle Disease

    MedlinePlus

    ... are: • cramping in muscles (probably related to insufficient energy supply for muscles) • pain in muscles • weakness of exercised muscles • dark urine that looks like cola, following exercise (seek ...

  7. Isotretinoin-induced acute severe myopathy involving pelvic girdle muscles: A case report

    PubMed Central

    Sameem, Farah; Semira

    2016-01-01

    Oral isotretinoin has been in widespread use for more than three decades. It causes numerous side effects; skin and mucous membrane being commonly involved. Musculoskeletal adverse effects are also known to occur, but pelvic girdle myopathy is rarely reported. We report myopathy involving pelvic girdle muscles in a young male who received oral isotretinoin for folliculitis decalvans. PMID:27721552

  8. Muscle Session Summary

    NASA Technical Reports Server (NTRS)

    Baldwin, Kenneth; Feeback, Daniel

    1999-01-01

    Presentations from the assembled group of investigators involved in specific research projeects related to skeletal muscle in space flight can categorized in thematic subtopics: regulation of contractile protein phenotypes, muscle growth and atrophy, muscle structure: injury, recovery,and regeneration, metabolism and fatigue, and motor control and loading factors.

  9. β-Carotene Increases Muscle Mass and Hypertrophy in the Soleus Muscle in Mice.

    PubMed

    Kitakaze, Tomoya; Harada, Naoki; Imagita, Hidetaka; Yamaji, Ryoichi

    2015-01-01

    Supplements and naturally occurring nutraceuticals effective for maintenance or enhancement of skeletal muscle mass are expected to contribute to prevention of decreased mobility and increased risk of developing metabolic diseases. However, information about available food components remains widely unavailable. In the present study, we investigated the effects of dietary β-carotene on the quantity and quality of skeletal muscle under physiological conditions. Male ddY mice (8 wk old) were orally administered β-carotene (0.5 mg once daily) for 14 d. Dietary β-carotene had no influence on body weight, but increased the soleus muscle/body weight ratio. The cross-sectional area (CSA) in muscle fibers of the soleus muscle was increased, indicating that administration of β-carotene induces muscle hypertrophy. In the soleus muscle of the β-carotene-administered mice, twitch force tended to be increased (p=0.06) and tetanic force was significantly increased, whereas specific force (force per CSA) remained unchanged. Dietary β-carotene increased the mRNA level of insulin-like growth factor 1 (Igf-1) as its splicing variant Igf-1ea, but had no influence on the liver Igf-1 mRNA level or serum IGF-1 level. β-Carotene promoted protein synthesis in the soleus muscle and reduced levels of ubiquitin conjugates, but had no influence on the mRNA levels of two atrogenes, Atrogin-1 and Murf1. On the other hand, β-carotene had no influence on the processing of the autophagy marker protein light chain 3. These results indicate that in mice, administration of β-carotene increases mass and induces functional hypertrophy in the soleus muscle, perhaps by promoting IGF-1-mediated protein synthesis and by reducing ubiquitin-mediated protein degradation. PMID:26875490

  10. Oral Cancer Foundation

    MedlinePlus

    ... Famous People Famous historical Arts & Entertainment Sports figures ... The Oral Cancer Foundation The Oral Cancer Foundation is a national public service, non-profit entity designed to reduce suffering ...

  11. Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage.

    PubMed

    Dalakas, M C; Leon-Monzon, M E; Bernardini, I; Gahl, W A; Jay, C A

    1994-04-01

    The use of zidovudine (AZT) for the treatment of acquired immunodeficiency syndrome (AIDS) induces a DNA-depleting mitochondrial myopathy, which is histologically characterized by the presence of muscle fibers with "ragged-red"-like features, red-rimmed or empty cracks, granular degeneration, and rods (AZT fibers). Because dysfunctioning muscle mitochondria may lead to defects of beta-oxidation of fatty acids, we examined the degree of neutral fat accumulation and muscle carnitine levels in the muscle biopsy specimens from 21 patients with AZT-induced myopathic symptoms of varying severity. Six patients with no AZT fibers had normal endomyofibrillar lipid deposits and muscle carnitine levels; 7 patients with fewer than 5 AZT fibers per field had a mild (+) to moderate (++) increase in lipid droplets, and reduced muscle carnitine levels (3 patients); and 8 patients with more than 5 AZT fibers had severe muscle changes, a ++ to marked ( ) increase in lipid droplets, and reduced muscle carnitine levels (6 patients). Serial sections showed lipid globules often within "cracks" or vacuoles of the abnormal muscle fibers. We conclude that the muscle mitochondrial impairment caused by AZT results in (1) accumulation of lipid within the muscle fibers owing to poor utilization of long-chain fatty acids, (2) reduction of muscle carnitine levels probably due to decreased carnitine uptake by the muscle, and (3) depletion of energy stores within the muscle fibers. The findings may have potential therapeutic implications in the treatment of AZT-induced myopathic symptoms using oral carnitine supplementation.

  12. Oral Steroids for Dermatitis.

    PubMed

    Fisher, Andrew D; Clarke, Jesse; Williams, Timothy K

    2015-01-01

    Contact/allergic dermatitis is frequently treated inappropriately with lower-than-recommended doses or inadequate duration of treatment with oral and intramuscular glucocorticoids. This article highlights a case of dermatitis in a Ranger Assessment and Selection Program student who was improperly treated over 2 weeks with oral steroids after being bit by Cimex lectularius, commonly known as bed bugs. The article also highlights the pitfalls of improper oral steroid dosing and provides reasoning for longer-duration oral steroid treatment.

  13. HAD Oral History Project

    NASA Astrophysics Data System (ADS)

    Holbrook, Jarita

    2014-01-01

    The Historical Astronomy Division is the recipient of an American Institute of Physics Neils Bohr Library Grant for Oral History. HAD has assembled a team of volunteers to conduct oral history interviews since May 2013. Each oral history interview varies in length between two and six hours. This presentation is an introduction to the HAD Oral History Project and the activities of the team during the first six months of the grant.

  14. Oral Steroids for Dermatitis.

    PubMed

    Fisher, Andrew D; Clarke, Jesse; Williams, Timothy K

    2015-01-01

    Contact/allergic dermatitis is frequently treated inappropriately with lower-than-recommended doses or inadequate duration of treatment with oral and intramuscular glucocorticoids. This article highlights a case of dermatitis in a Ranger Assessment and Selection Program student who was improperly treated over 2 weeks with oral steroids after being bit by Cimex lectularius, commonly known as bed bugs. The article also highlights the pitfalls of improper oral steroid dosing and provides reasoning for longer-duration oral steroid treatment. PMID:26125159

  15. Myosin Heavy Chain Composition of the Human Genioglossus Muscle

    ERIC Educational Resources Information Center

    Daugherty, Megan; Luo, Qingwei; Sokoloff, Alan J.

    2012-01-01

    Background: The human tongue muscle genioglossus (GG) is active in speech, swallowing, respiration, and oral transport, behaviors encompassing a wide range of tongue shapes and movement speeds. Studies demonstrate substantial diversity in patterns of human GG motor unit activation, but whether this is accompanied by complex expression of muscle…

  16. Medullary carcinoma of the thyroid, pancreatic nesidioblastosis and microadenosis, and pancreatic polypeptide hypersecretion: a new association and clinical and hormonal responses to long-acting somatostatin analog SMS 201-995.

    PubMed

    Jerkins, T W; Sacks, H S; O'Dorisio, T M; Tuttle, S; Solomon, S S

    1987-06-01

    We describe a 63-yr-old man with disseminated medullary carcinoma of the thyroid and pancreatic nesidioblastosis and microadenosis with pancreatic polypeptide (PP) hypersecretion. His major symptoms were watery diarrhea, flushing, and abdominal bloating; these and the elevated plasma PP levels did not change after resection of the distal two thirds of the pancreas, which contained a 2-cm mass of nesidioblastotic tissue. Postoperatively, a long-acting somatostatin analog, SMS 201-995 (100 micrograms/day), normalized PP secretion acutely and chronically (7 months) and ameliorated his symptoms. The analog had no side-effects and did not alter glucose tolerance, calcitonin hypersecretion, or growth of the medullary carcinoma, but it did inhibit GH secretion. After withdrawal from therapy for 1 month, PP hypersecretion and all symptoms except diarrhea recurred. The coexistence of medullary carcinoma of the thyroid and PP cell nesidioblastosis represents a new variant of the overlap syndromes between multiple endocrine neoplasia types I and II. Patients with medullary carcinoma and unexplained watery diarrhea should have fasting gastroenteropancreatic hormone assays done to screen for a potential gastrointestinal or pancreatic origin for the diarrhea. PMID:2883196

  17. Glucocorticoids and Skeletal Muscle.

    PubMed

    Bodine, Sue C; Furlow, J David

    2015-01-01

    Glucocorticoids are known to regulate protein metabolism in skeletal muscle, producing a catabolic effect that is opposite that of insulin. In many catabolic diseases, such as sepsis, starvation, and cancer cachexia, endogenous glucocorticoids are elevated contributing to the loss of muscle mass and function. Further, exogenous glucocorticoids are often given acutely and chronically to treat inflammatory conditions such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, resulting in muscle atrophy. This chapter will detail the nature of glucocorticoid-induced muscle atrophy and discuss the mechanisms thought to be responsible for the catabolic effects of glucocorticoids on muscle. PMID:26215994

  18. Oxidative Metabolism in Muscle

    NASA Astrophysics Data System (ADS)

    Ferrari, M.; Binzoni, T.; Quaresima, V.

    1997-06-01

    Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantages and problems of near-infrared spectroscopy measurements, in resting and exercising skeletal muscles studies, are discussed through some representative examples.

  19. Developing Oral Communication Skills.

    ERIC Educational Resources Information Center

    Washington Office of the State Superintendent of Public Instruction, Olympia.

    Intended for use by both elementary and secondary school teachers, the two papers in this report stress the importance of developing students' oral and written communication skills. The first paper, "Relationship of Oral Communication to Reading," by Phil Backlund and John Johnson, argues that ability in oral communication is a prerequisite to the…

  20. Bibliography on Oral History.

    ERIC Educational Resources Information Center

    Waserman, Manfred J., Comp.

    This annotated bibliography covers articles and books dealing with oral history published between 1950 and 1970. In addition to works treating oral history as a methodology for historical discovery, the guide includes a separate annotated list of twenty selected books that use oral history material in the development of their themes and…

  1. Oral Contraceptives and Cancer Risk

    MedlinePlus

    ... oral contraceptives are available in the United States today? How could oral contraceptives influence cancer risk? How ... oral contraceptives are available in the United States today? Two types of oral contraceptives (birth control pills) ...

  2. Head, Neck, and Oral Cancer

    MedlinePlus

    ... Neck and Oral Pathology Head, Neck and Oral Pathology Close to 42,000 Americans will be diagnosed ... Neck and Oral Pathology Head, Neck and Oral Pathology Close to 42,000 Americans will be diagnosed ...

  3. Oral health-related quality of life and oral status in a German working population.

    PubMed

    Walter, Michael H; Schuette, Ursula; Raedel, Michael; Koch, Rainer; Wolf, Burkhard; Scheuch, Klaus; Kirch, Wilhelm

    2011-12-01

    The study aim was to identify predictors of impaired oral health-related quality of life (OHRQoL). Employees of five companies were offered a clinical full-mouth examination. Oral health-related quality of life was measured with the German version of the Oral Health Impact Profile (OHIP) and summarized as additive scores (OHIP-ADD) and as prevalence of negative impacts (OHIP-SC). Two logistic regression models were developed for the odds of increased scores of the target variables OHIP-ADD and OHIP-SC. The target variables were dichotomized, and for the OHIP-ADD, the cut-off point for having impaired OHRQoL was heuristically defined as OHIP-ADD > 34. For the OHIP-SC, the corresponding threshold was OHIP-SC > 0. In the model for the OHIP-ADD, female gender, impaired aesthetics, few posterior occluding pairs, and painful masticatory muscles proved to be significant independent variables. For the OHIP-SC, female gender, impaired aesthetics, painful masticatory muscles, joint sounds, missing mandibular teeth, and carious teeth were significant. This cross-sectional study showed that within the models for both OHIP-ADD and OHIP-SC the high-risk person for impaired OHRQoL is a woman with impaired aesthetics and painful masticatory muscles. PMID:22112035

  4. Essentials of oral cancer

    PubMed Central

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators. PMID:26617944

  5. Essentials of oral cancer.

    PubMed

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators. PMID:26617944

  6. Infant oral health and oral habits.

    PubMed

    Nowak, A J; Warren, J J

    2000-10-01

    Many oral diseases and conditions, including dental caries (cavities) and malocclusions, have their origins early in life. Prudent anticipatory guidance by the medical and dental professions can help prevent many of the more common oral health problems. This article provides information on the rationale for early dental examination and instructions for pediatric and family practitioners in scheduling and conducting an early oral intervention appointment. In addition, feeding practices, non-nutritive sucking, mouth breathing, and bruxing are discussed, including their effects on orofacial growth and development.

  7. A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups

    PubMed Central

    Randolph, Matthew E.; Pavlath, Grace K.

    2015-01-01

    The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The biology of muscle stem cells varies depending on the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease. PMID:26500547

  8. Sternomastoid muscle fatigue and twitch maximum relaxation rate in patients with steroid dependent asthma.

    PubMed Central

    Mak, V. H.; Bugler, J. R.; Spiro, S. G.

    1993-01-01

    BACKGROUND--Long term oral corticosteroid treatment is a cause of myopathy of the skeletal muscles. The effect of long term treatment with oral corticosteroids on the respiratory muscles is uncertain. Respiratory muscle function and fatigue in sternomastoid muscle were investigated in a group of patients with chronic severe asthma who were taking oral corticosteroids. The results were compared with those from a group of patients with chronic airflow limitation who were not taking oral steroids. METHODS--Twelve patients with chronic severe asthma, taking a mean daily dosage of 8 mg of prednisolone for a mean (SD) of 16.8 (9.1) years, were compared with patients with chronic airflow limitation and individually matched for sex, age, and severity of airflow limitation. Lung function tests, maximal mouth pressures, and quadriceps and sternomastoid muscle strength were measured. The sternomastoid muscle was fatigued by maximal headlift exercise to 70% of initial headlift force and the endurance time noted. Sternomastoid fatigue was assessed by twitch maximum relaxation rate (TMRR) measured in the fresh state and for 30 minutes after exercise. RESULTS--There was no significant difference between the control group and the corticosteroid group for maximal mouth pressures, fresh state TMRR, and quadriceps and sternomastoid strength. The control group had a significantly longer mean (SD) endurance time than the corticosteroid group (121 (47) s v 86 (24) s), and also had significantly less slowing and faster recovery of the TMRR after exercise. The slowing and recovery of the TMRR in the corticosteroid group, however, was similar to that previously reported for normal subjects. CONCLUSION--Respiratory muscle weakness does not occur more often in patients taking oral corticosteroids. The corticosteroid group was more prone to fatigue than the control group, but was similar to normal subjects. This suggests that chronic airflow limitation may produce a training effect on the

  9. Long-term treatment of central precocious puberty with a long-acting analogue of luteinizing hormone release hormone (D-Tryp6-GnRH) in monthly injections. Its possible use in normal puberty.

    PubMed

    Marcondes, J A; Abujamra, A C; Minanni, S L; Mendonca, B B; Nery, M; Lerario, A C; Pereira, M A; Abelin, N; Wajchenberg, B L

    1993-02-01

    The gonadotropin-releasing-hormone-like agonist D-Tryp6-GnRH (GnRHa) has been shown to induce reversible suppression of gonadotropins and gonadal steroids in patients with central precocious puberty. We examined the effect of a long-acting preparation of GnRHa in biodegradable microcapsules. D-Tryptophane6-GnRH, administered intramuscularly at 1 month intervals, for 12 consecutive months, on growth and skeletal maturation in 3 girls and 4 boys with neurogenic or idiopathic precocious puberty. Suppression of gonadotropin release after GnRH stimulation and gonadal steroids was maintained in all subjects. Growth velocity fell from a mean rate (+/- SEM) or 8.60 +/- 0.75 cm/year before treatment to 5.81 +/- 0.60 cm/year (p < 0.005) after 1 year. Bone age advanced a mean of 8.0 +/- 0.45 months during treatment, suggesting an increase in predicted height from the ratio delta bone age/delta chronological age. Two subjects, one of them with compensated Bartter's syndrome with normal hypothalamic pituitary-gonadal-axis, received the analogue to delay pubertal growth with the hope to improve final height. In the first one, the growth velocity fell from 9.9 cm/year to 8 cm/year and delta bone age/delta chronological age decreased from 1.28 to 1.0 and in the other subject, the growth velocity fell from 12 cm/year to 6.0 cm/year in the last year of treatment and delta bone age/delta chronological age fell from 3.2 to 0.75, indicating an improvement in predicted height.

  10. A cross-sectional study of the identification of prevalent asthma and chronic obstructive pulmonary disease among initiators of long-acting β-agonists in health insurance claims data

    PubMed Central

    2014-01-01

    Background Claims data are potentially useful for identifying long-acting β-agonist (LABA) use by patients with asthma, a practice that is associated with increased mortality. We evaluated the accuracy of claims data for classifying prevalent asthma and chronic obstructive pulmonary disease (COPD) among initiators of LABAs. Methods This study included adult LABA initiators during 2005–2008 in a US commercial health plan. Diagnosis codes from the 6 months before LABA initiation identified potential asthma or COPD and a physician adjudicated case status using abstracted medical records. We estimated the positive predictive value (PPV) and 95% confidence intervals (CI) of covariate patterns for identifying asthma and COPD. Results We sought 520 medical records at random from 225,079 LABA initiators and received 370 (71%). The PPV for at least one asthma claim was 74% (CI 63–82), and decreased as age increased. Having at least one COPD claim resulted in a PPV of 82% (CI 72–89), and of over 90% among older patients, men, and recipients of inhaled anticholinergic drugs. Only 2% (CI 0.2–7.6) of patients with a claim for COPD alone were found to have both COPD and asthma, while 9% (CI 4–16) had asthma only. Twenty-one percent (CI 14–30) of patients with claims for both diagnoses had both conditions. Among patients with no asthma or COPD claims, 62% (CI 50–72) had no confirmed diagnosis and 29% (CI 19–39) had confirmed asthma. Conclusions Subsets of patients with asthma, COPD, and both conditions can be identified and differentiated using claims data, although categorization of the remaining patients is infeasible. Safety surveillance for off-label use of LABAs must account for this limitation. PMID:24645984

  11. Bronchial reversibility with a short-acting β2-agonist predicts the FEV1 response to administration of a long-acting β2-agonist with inhaled corticosteroids in patients with bronchial asthma.

    PubMed

    Ohwada, Akihiko; Inami, Kei; Onuma, Emi; Matsumoto-Yamazaki, Mariko; Atsuta, Ryo; Takahashi, Kazuhisa

    2011-07-01

    A long-acting β2-agonist (LABA) combined with an inhaled corticosteroid (ICS) is frequently prescribed as initial therapy in steroid-naïve asthma patients because of its effective control of symptoms and improvement of pulmonary function. However, it is unclear which patients will be responsive to LABAs and whether bronchial responsiveness to LABAs is similar to that to short-acting β2-agonists (SABAs) in a clinical setting. Therefore, the goal of the present study was to compare the changes in spirometric parameters after SABA (salbutamol) inhalation to those after 1-month LABA/ICS (salmeterol/fluticasone propionate) therapy. Spirometric changes were evaluated as absolute values, as the percentage of predicted normal values and as the percentage of baseline values after salbutamol inhalation or 1-month LABA/ICS therapy in 45 patients with asthma. Compared to SABA inhalation, LABA/ICS therapy produced significant improvements in forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF), forced expiratory flow at 50% of vital capacity expired (FEF50%) from baseline (expressed as the percentage predicted) in all patients. FEV1 and the FEV1/forced vital capacity (FVC) ratio after SABA or LABA/ICS therapy were inversely related to the corresponding baseline values. Analysis of spirometric changes after SABA inhalation showed that FEV1 was the best among spirometric parameters, such as PEF, correlated with responsiveness to LABA/ICS therapy. Reversibility of FEV1 with SABA inhalation predicts the spirometric response to LABA/ICS as initial therapy in patients with bronchial asthma. LABA/ICS therapy had a greater effect on bronchial reversibility in asthmatic patients, compared to SABA inhalation. This suggested that evaluation of bronchial reversibility after LABA/ICS therapy would be superior to that after SABA inhalation.

  12. Can asthma treatment in sports be doping? The effect of the rapid onset, long-acting inhaled beta2-agonist formoterol upon endurance performance in healthy well-trained athletes.

    PubMed

    Carlsen, K H; Hem, E; Stensrud, T; Held, T; Herland, K; Mowinckel, P

    2001-07-01

    Inhaled beta2-agonists have been subject to restrictions in relationship to sports due to fear of possible improvement in endurance performance. According to the international doping regulations only inhaled salbutamol, terbutaline and salmeterol are allowed for use in sports. Formoterol is a recently introduced rapid onset-long-acting inhaled beta2-agonist. The main aim of the present randomized, double-blind placebo-controlled study was to investigate possible improvement in endurance performance of inhaled formoterol in 24 healthy well-trained competitive male athletes, 21-29 years old. Lung function (flow-volume loops) was measured before, 15 min after each inhaled study drug and before and repeatedly after exercise. On day 1, maximum oxygen uptake (VO2max), peak ventilation (VEpeak) and running time till exhaustion were measured and used to determine the exercise load on days 2 and 3. On days 2 and 3 the subjects inhaled the study drugs, rested for 1 h, then exercised, and VO2max, VEpeak and running time until exhaustion were determined. Inhaled formoterol did not improve any parameter of endurance performance. On the other hand a statistically significant, although not clinically significant (0.05 ml(-1) min kg(-1)), change was found in estimated difference of VO2max between formoterol and placebo in favour of placebo. Lung function increased significantly after inhaled formoterol, and after exercise also for placebo, but without differences between the beta2-agonist and placebo after exercise. In conclusion, inhaled formoterol did not improve endurance performance compared to placebo.

  13. Darbepoetin alpha, a long-acting erythropoeitin derivate, does not alter LPS evoked myocardial depression and gene expression of Bax, Bcl-Xs, Bcl-XL, Bcl-2, and TNF-alpha.

    PubMed

    Brendt, Peter; Frey, Ulrich; Adamzik, Michael; Schäfer, Simon T; Peters, Jürgen

    2009-01-01

    Darbepoetin alpha (DA), a long-acting erythropoietin derivative stimulating erythropoiesis, can, by antiapoptotic effects, mitigate myocardial I/R injury. We tested the hypothesis that DA treatment improves left ventricular function (LV) in LPS evoked cardiomyopathy and alters gene expression of apoptosis-regulating proteins (Bcl-XL, Bcl-2, Bax, and Bcl-Xs) and TNF-alpha. In a prospective, controlled, randomized study in Lewis rats (n = 56; 8 groups), myocardial depression was evoked by LPS administration (serotype O127:B8; 10 mg/kg, i.p.). Darbepoetin alpha or vehicle was injected either 24 h before (pretreatment) or 2 h after LPS injection (treatment). Hearts were isolated 8 h after LPS injection, perfused (Krebs-Henseleit solution) in a Langendorff apparatus, and LV developed pressure and its derivatives were measured. For gene expression analysis, real-time polymerase chain reaction of LV specimen was performed. LPS decreased LV developed pressure (-64.6 +/- 7.9 mmHg) and its derivates by more than 60% in comparison to vehicle (P < 0,01), but this effect was not attenuated by DA pretreatment or DA treatment. LPS administration increased gene expression of Bcl-Xs, Bax, and TNF-alpha, but this was not altered by DA pretreatment. Furthermore, there was no effect on Bcl-Xl and Bcl-2 expression by DA alone. Whereas proapoptotic genes of the myocardium are up-regulated in LPS-induced cardiomyopathy, neither DA pretreatment nor treatment has significant effects on LV function or gene expression. This may suggest cardiac resistance to darbepoetin in LPS-mediated sepsis.

  14. Muscle development and obesity

    PubMed Central

    2008-01-01

    The formation of skeletal muscle from the epithelial somites involves a series of events triggered by temporally and spatially discrete signals resulting in the generation of muscle fibers which vary in their contractile and metabolic nature. The fiber type composition of muscles varies between individuals and it has now been found that there are differences in fiber type proportions between lean and obese animals and humans. Amongst the possible causes of obesity, it has been suggested that inappropriate prenatal environments may ‘program’ the fetus and may lead to increased risks for disease in adult life. The characteristics of muscle are both heritable and plastic, giving the tissue some ability to adapt to signals and stimuli both pre and postnatally. Given that muscle is a site of fatty acid oxidation and carbohydrate metabolism and that its development can be changed by prenatal events, it is interesting to examine the possible relationship between muscle development and the risk of obesity. PMID:19279728

  15. ANG II is required for optimal overload-induced skeletal muscle hypertrophy

    NASA Technical Reports Server (NTRS)

    Gordon, S. E.; Davis, B. S.; Carlson, C. J.; Booth, F. W.

    2001-01-01

    ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT(1)) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225-250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle (experiment 1) or both the gastrocnemius and plantaris muscles (experiment 2). In experiment 1 (n = 10/group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals (experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT(1) receptor-dependent pathway.

  16. Muscle Changes in Aging

    PubMed Central

    Siparsky, Patrick N.; Kirkendall, Donald T.; Garrett, William E.

    2014-01-01

    Muscle physiology in the aging athlete is complex. Sarcopenia, the age-related decrease in lean muscle mass, can alter activity level and affect quality of life. This review addresses the microscopic and macroscopic changes in muscle with age, recognizes contributing factors including nutrition and changes in hormone levels, and identifies potential pharmacologic agents in clinical trial that may aid in the battle of this complex, costly, and disabling problem. Level of Evidence: Level 5. PMID:24427440

  17. Pharyngeal Satellite Cells Undergo Myogenesis Under Basal Conditions and Are Required for Pharyngeal Muscle Maintenance.

    PubMed

    Randolph, Matthew E; Phillips, Brittany L; Choo, Hyo-Jung; Vest, Katherine E; Vera, Yandery; Pavlath, Grace K

    2015-12-01

    The pharyngeal muscles of the nasal, oral, and laryngeal pharynxes are required for swallowing. Pharyngeal muscles are preferentially affected in some muscular dystrophies yet spared in others. Muscle stem cells, called satellite cells, may be critical factors in the development of pharyngeal muscle disorders; however, very little is known about pharyngeal satellite cells (PSC) and their role in pharyngeal muscles. We show that PSC are distinct from the commonly studied hindlimb satellite cells both transcriptionally and biologically. Under basal conditions PSC proliferate, progress through myogenesis, and fuse with pharyngeal myofibers. Furthermore, PSC exhibit biologic differences dependent on anatomic location in the pharynx. Importantly, PSC are required to maintain myofiber size and myonuclear number in pharyngeal myofibers. Together, these results demonstrate that PSC are critical for pharyngeal muscle maintenance and suggest that satellite cell impairment could contribute to pharyngeal muscle pathology associated with various muscular dystrophies and aging.

  18. An artificial muscle computer

    NASA Astrophysics Data System (ADS)

    Marc O'Brien, Benjamin; Alexander Anderson, Iain

    2013-03-01

    We have built an artificial muscle computer based on Wolfram's "2, 3" Turing machine architecture, the simplest known universal Turing machine. Our computer uses artificial muscles for its instruction set, output buffers, and memory write and addressing mechanisms. The computer is very slow and large (0.15 Hz, ˜1 m3); however by using only 13 artificial muscle relays, it is capable of solving any computable problem given sufficient memory, time, and reliability. The development of this computer shows that artificial muscles can think—paving the way for soft robots with reflexes like those seen in nature.

  19. MUSCLE INJURIES IN ATHLETES

    PubMed Central

    Barroso, Guilherme Campos; Thiele, Edilson Schwansee

    2015-01-01

    This article had the aim of demonstrating the physiology, diagnosis and treatment of muscle injuries, focusing on athletes and their demands and expectations. Muscle injuries are among the most common complaints in orthopedic practice, occurring both among athletes and among non-athletes. These injuries present a challenge for specialists, due to the slow recovery, during which time athletes are unable to take part in training and competitions, and due to frequent sequelae and recurrences of the injuries. Most muscle injuries (between 10% and 55% of all injuries) occur during sports activities. The muscles most commonly affected are the ischiotibial, quadriceps and gastrocnemius. These muscles go across two joints and are more subject to acceleration and deceleration forces. The treatment for muscle injuries varies from conservative treatment to surgery. New procedures are being used, like the hyperbaric chamber and the use of growth factors. However, there is still a high rate of injury recurrence. Muscle injury continues to be a topic of much controversy. New treatments are being researched and developed, but prevention through muscle strengthening, stretching exercises and muscle balance continues to be the best “treatment”. PMID:27027021

  20. Oral carnitine therapy in children with cystinosis and renal Fanconi syndrome

    SciTech Connect

    Gahl, W.A.; Bernardini, I.; Dalakas, M.; Rizzo, W.B.; Harper, G.S.; Hoeg, J.M.; Hurko, O.; Bernar, J.

    1988-02-01

    11 children with either cystinosis or Lowe's syndrome had a reduced content of plasma and muscle carnitine due to renal Fanconi syndrome. After treatment with oral L-carnitine, 100 mg/kg per d divided every 6 h, plasma carnitine concentrations became normal in all subjects within 2 d. Initial plasma free fatty acid concentrations, inversely related to free carnitine concentrations, were reduced after 7-20 mo of carnitine therapy. Muscle lipid accumulation, which varied directly with duration of carnitine deficiency (r = 0.73), improved significantly in three of seven rebiopsied patients after carnitine therapy. One Lowe's syndrome patient achieved a normal muscle carnitine level after therapy. Muscle carnitine levels remained low in all cystinosis patients, even though cystinotic muscle cells in culture took up L-(/sup 3/H)carnitine normally. The half-life of plasma carnitine for cystinotic children given a single oral dose approximated 6.3 h; 14% of ingested L-carnitine was excreted within 24 h. Studies in a uremic patient with cystinosis showed that her plasma carnitine was in equilibrium with some larger compartment and may have been maintained by release of carnitine from the muscle during dialysis. Because oral L-carnitine corrects plasma carnitine deficiency, lowers plasma free fatty acid concentrations, and reverses muscle lipid accumulation in some patients, its use as therapy in renal Fanconi syndrome should be considered. However, its efficacy in restoring muscle carnitine to normal, and the optimal dosage regimen, have yet to be determined.

  1. Longitudinal Multilevel Modeling of Facial Pain, Muscle Tension, and Stress.

    PubMed

    Glaros, A G; Marszalek, J M; Williams, K B

    2016-04-01

    The role of masticatory muscle activation on pain in temporomandibular muscle and joint disorders (TMJD) is controversial. This single-group, prospective panel study examined the relationships among masticatory muscle tension, emotional distress, and TMJD pain in a sample of 7,023 observations obtained from 171 individuals using longitudinal multilevel modeling. Three main hypotheses were tested. The first posited that emotional distress and muscle tension directly influenced pain (hypothesis 1a: Distress → TMJD Pain; hypothesis 1b: Muscle Tension → TMJD Pain). The second posited that emotional distress directly influenced muscle tension (Distress → Muscle Tension), and the third posited that the effect of emotional distress on pain was mediated by muscle tension (Distress → Muscle Tension → TMJD pain). We also examined the fit of the data to possible alternative models. All the data used in this study were collected via an experience sampling methodology. The fit of the preferred models was better than that of the alternative models, with the preferred models explaining large proportions of the data, especially for level 2 variance (hypothesis 1a = 41% variance; hypothesis 1b = 69% variance; hypothesis 2 = 48% variance). In the mediation model, the addition of muscle tension to the model reduced the impact of emotional distress. The findings support a causal role for masticatory muscle tension in TMJD pain. Clinically, the results suggest that addressing tension and other oral parafunctions in those diagnosed with TMJDs should be an important part of the conservative, noninvasive care of individuals diagnosed with the myofascial pain or arthralgia of TMJD.

  2. Advances in Oral Coagulants

    PubMed Central

    2013-01-01

    This article reviews current and future treatment practices concerning oral anticoagulants. In the second decade of the 21st millennium clinicians can finally treat thrombotic disease with long-awaited new oral anticoagulant medications. In addition, improvements have been made in managing warfarin, the traditional but far from obsolete medication. The first part of this review will cover current advances with warfarin treatment. The second portion will discuss specific active coagulation factor inhibitors, the new oral anticoagulants.

  3. Ischemia causes muscle fatigue

    NASA Technical Reports Server (NTRS)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  4. Citrulline malate limits increase in muscle fatigue induced by bacterial endotoxins.

    PubMed

    Goubel, F; Vanhoutte, C; Allaf, O; Verleye, M; Gillardin, J M

    1997-03-01

    Citrulline malate is known to improve performance in weakened muscles. The present experiment was designed to test the hypothesis that citrulline malate can limit the effect of endotoxins on muscle fatigability. Endotoxemia was induced in rats by injection of lipopolysaccharides from Klebsiella pneumoniae. Resistance to fatigue was quantified by measuring tension production during repetitive electrical stimulation of the isolated epitrochlearis muscle. Oral treatment by citrulline malate was found to increase resistance to fatigue in infected rats, whereas twitch tension was not modified. This demonstrates the efficacy of citrulline malate for limiting an increase in muscle fatigue elicited with bacterial endotoxins. PMID:9164703

  5. Towards understanding oral health.

    PubMed

    Zaura, Egija; ten Cate, Jacob M

    2015-01-01

    During the last century, dental research has focused on unraveling the mechanisms behind various oral pathologies, while oral health was typically described as the mere absence of oral diseases. The term 'oral microbial homeostasis' is used to describe the capacity of the oral ecosystem to maintain microbial community stability in health. However, the oral ecosystem itself is not stable: throughout life an individual undergoes multiple physiological changes while progressing through infancy, childhood, adolescence, adulthood and old age. Recent discussions on the definition of general health have led to the proposal that health is the ability of the individual to adapt to physiological changes, a condition known as allostasis. In this paper the allostasis principle is applied to the oral ecosystem. The multidimensionality of the host factors contributing to allostasis in the oral cavity is illustrated with an example on changes occurring in puberty. The complex phenomenon of oral health and the processes that prevent the ecosystem from collapsing during allostatic changes in the entire body are far from being understood. As yet individual components (e.g. hard tissues, microbiome, saliva, host response) have been investigated, while only by consolidating these and assessing their multidimensional interactions should we be able to obtain a comprehensive understanding of the ecosystem, which in turn could serve to develop rational schemes to maintain health. Adapting such a 'system approach' comes with major practical challenges for the entire research field and will require vast resources and large-scale multidisciplinary collaborations. PMID:25871419

  6. Oral microbiota and cancer

    PubMed Central

    Meurman, Jukka H.

    2010-01-01

    Inflammation caused by infections may be the most important preventable cause of cancer in general. However, in the oral cavity the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites and certain oral bacterial species have been linked with malignancies but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer, such as pancreatic and gastrointestinal cancer. Furthermore, several oral micro-organisms are capable of converting alcohol to carcinogenic acetaldehyde which also may partly explain the known association between heavy drinking, smoking, poor oral health and the prevalence of oral and upper gastrointestinal cancer. A different problem is the cancer treatment-caused alterations in oral microbiota which may lead to the emergence of potential pathogens and subsequent other systemic health problems to the patients. Hence clinical guidelines and recommendations have been presented to control oral microbiota in patients with malignant disease, but also in this area the scientific evidence is weak. More controlled studies are needed for further conclusion. PMID:21523227

  7. Food oral processing: conversion of food structure to textural perception.

    PubMed

    Koç, H; Vinyard, C J; Essick, G K; Foegeding, E A

    2013-01-01

    Food oral processing includes all muscle activities, jaw movements, and tongue movements that contribute to preparing food for swallowing. Simultaneously, during the transformation of food structure to a bolus, a cognitive representation of food texture is formed. These physiological signals detected during oral processing are highly complex and dynamic in nature because food structure changes continuously due to mechanical and biochemical breakdown coupled with the lubricating action of saliva. Multiple and different sensations are perceived at different stages of the process. Although much work has focused on factors that determine mechanical (e.g., rheological and fracture) and sensory properties of foods, far less attention has been paid to linking food transformations that occur during oral processing with sensory perception of texture. Understanding how food structure influences specific patterns of oral processing and how these patterns relate to specific textural properties and their cognitive representations facilitates the design of foods that are nutritious, healthy, and enjoyable.

  8. Structure of Skeletal Muscle

    MedlinePlus

    ... Cells, Tissues, & Membranes Cell Structure & Function Cell Structure Cell Function Body Tissues Epithelial Tissue Connective Tissue Muscle Tissue ... nerves. This is directly related to the primary function of skeletal muscle, ... an impulse from a nerve cell. Generally, an artery and at least one vein ...

  9. Autoimmune muscle disease.

    PubMed

    Mammen, Andrew

    2016-01-01

    Patients with polymyositis (PM), dermatomyositis (DM), and immune-mediated necrotizing myopathy (IMNM) present with the subacute onset of symmetric proximal muscle weakness, elevated muscle enzymes, myopathic findings on electromyography, and autoantibodies. DM patients are distinguished by their cutaneous manifestations. Characteristic features on muscle biopsy include the invasion of nonnecrotic muscle fibers by T cells in PM, perifascicular atrophy in DM, and myofiber necrosis without prominent inflammation in IMNM. Importantly, these are regarded as autoimmune diseases and most patients respond partially, if not completely, to immunosuppressive therapy. Patients with inclusion body myositis (IBM) usually present with the insidious onset of asymmetric weakness in distal muscles (e.g., wrist flexors, and distal finger flexors), often when more proximal muscle groups are relatively preserved. Although IBM muscle biopsies usually have focal invasion of myofibers by lymphocytes, the majority of IBM biopsies also include rimmed vacuoles. While most IBM patients do have autoantibodies, treatment with immunosuppressive agents does not improve their clinical course. Along with the presence of abnormally aggregated proteins on muscle biopsy, the refractory nature and relentless course of IBM suggest that the underlying pathophysiology may include a dominant myodegenerative component. This chapter will focus on the epidemiology, clinical presentation, and treatment of the autoimmune myopathies and IBM. An emphasis will be placed on recent advances, indicating that these are a diverse family of diseases and that each of more than a dozen myositis autoantibodies is associated with a distinct clinical phenotype. PMID:27112692

  10. SMOOTH MUSCLE STEM CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well-studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, includ...

  11. Types of muscle tissue (image)

    MedlinePlus

    The 3 types of muscle tissue are cardiac, smooth, and skeletal. Cardiac muscle cells are located in ... heart, appear striated, and are under involuntary control. Smooth muscle fibers are located in walls of hollow ...

  12. Research opportunities in muscle atrophy

    NASA Technical Reports Server (NTRS)

    Herbison, G. J.; Talbot, J. M.

    1984-01-01

    A trophy of skeletal muscle; muscle a trophy associated with manned space flight; the nature, causes, and mechanisms of muscle atrophy associated with space flight, selected physiological factors, biochemical aspects, and countermeasures are addressed.

  13. A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study

    PubMed Central

    2014-01-01

    Background Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) – tiotropium and glycopyrronium. Previous studies have compared glycopyrronium with open-label tiotropium. In the GLOW5 study, we compare glycopyrronium with blinded tiotropium. Methods In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily. The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: –50 mL). Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment. Results 657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study. Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: –32, 31 mL). Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0–4 h post-dose versus tiotropium (all p < 0.001). FEV1 area under the curve from 0–4 h (AUC0–4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12. Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant). Patients on

  14. The Mayer Hashi Large-Scale Program to Increase Use of Long-Acting Reversible Contraceptives and Permanent Methods in Bangladesh: Explaining the Disappointing Results. An Outcome and Process Evaluation

    PubMed Central

    Rahman, Mizanur; Haider, M Moinuddin; Curtis, Sian L; Lance, Peter M

    2016-01-01

    ABSTRACT Background: Bangladesh has achieved a low total fertility rate of 2.3. Two-thirds of currently married women of reproductive age (CMWRA) want to limit fertility, and many women achieve their desired fertility before age 30. The incidence of unintended pregnancy and pregnancy termination is high, however. Long-acting reversible contraceptives (LARCs), consisting of the intrauterine device and implant, and permanent methods (PM), including female sterilization and vasectomy, offer several advantages in this situation, but only 8% of CMWRA or 13% of method users use these methods. Program: The Mayer Hashi (MH) program (2009–2013) aimed to improve access to and the quality of LARC/PM services in 21 of the 64 districts in Bangladesh. It was grounded in the SEED (supply–enabling environment–demand) Programming Model. Supply improvements addressed provider knowledge and skills, system strengthening, and logistics. Creating an enabling environment involved holding workshops with local and community leaders, including religious leaders, to encourage them to help promote demand for LARCs and PMs and overcome cultural barriers. Demand promotion encompassed training of providers in counseling, distribution of behavior change communication materials in the community and in facilities, and community mobilization. Methods: We selected 6 MH program districts and 3 nonprogram districts to evaluate the program. We used a before–after and intervention–comparison design to measure the changes in key contraceptive behavior outcomes, and we used a difference-in-differences (DID) specification with comparison to the nonprogram districts to capture the impact of the program. In addition to the outcome evaluation, we considered intermediate indicators that measured the processes through which the interventions were expected to affect the use of LARCs and PMs. Results: The use of LARCs/PMs among CMWRA increased between 2010 and 2013 in both program (from 5.3% to 7.5%) and

  15. The in vivo efficacy and side effect pharmacology of GS-5759, a novel bifunctional phosphodiesterase 4 inhibitor and long-acting β 2-adrenoceptor agonist in preclinical animal species.

    PubMed

    Salmon, Michael; Tannheimer, Stacey L; Gentzler, Terry T; Cui, Zhi-Hua; Sorensen, Eric A; Hartsough, Kimberly C; Kim, Musong; Purvis, Lafe J; Barrett, Edward G; McDonald, Jacob D; Rudolph, Karin; Doyle-Eisele, Melanie; Kuehl, Philip J; Royer, Christopher M; Baker, William R; Phillips, Gary B; Wright, Clifford D

    2014-08-01

    Bronchodilators are a central therapy for symptom relief in respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma, with inhaled β 2-adrenoceptor agonists and anticholinergics being the primary treatments available. The present studies evaluated the in vivo pharmacology of (R)-6-[[3-[[4-[5-[[2-Hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino]pent-1-ynyl]phenyl]carbamoyl]phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide (GS-5759), a novel bifunctional compound with both phosphodiesterase 4 (PDE4) inhibitor and long-acting β 2-adrenoceptor agonist (LABA) activity, which has been optimized for inhalation delivery. GS-5759 dose-dependently inhibited pulmonary neutrophilia in a lipopolysaccharide (LPS) aerosol challenge model of inflammation in rats with an ED50 ≤ 10 μg/kg. GS-5759 was also a potent bronchodilator with an ED50 of 0.09 μg/kg in guinea pigs and 3.4 μg/kg in dogs after methylcholine (MCh) and ragweed challenges respectively. In cynomolgus monkeys, GS-5759 was dosed as a fine-particle dry powder and was efficacious in the same dose range in both MCh and LPS challenge models, with an ED50 = 70 μg/kg for bronchodilation and ED50 = 4.9 μg/kg for inhibition of LPS-induced pulmonary neutrophilia. In models to determine therapeutic index (T.I.), efficacy for bronchodilation was evaluated against increased heart rate and GS-5759 had a T.I. of 700 in guinea pigs and >31 in dogs. In a ferret model of emesis, no emesis was seen at doses several orders of magnitude greater than the ED50 observed in the rat LPS inflammation model. GS-5759 is a bifunctional molecule developed for the treatment of COPD, which has both bronchodilator and anti-inflammatory activity and has the potential for combination as a triple therapy with a second compound, within a single inhalation device.

  16. Onion artificial muscles

    NASA Astrophysics Data System (ADS)

    Chen, Chien-Chun; Shih, Wen-Pin; Chang, Pei-Zen; Lai, Hsi-Mei; Chang, Shing-Yun; Huang, Pin-Chun; Jeng, Huai-An

    2015-05-01

    Artificial muscles are soft actuators with the capability of either bending or contraction/elongation subjected to external stimulation. However, there are currently no artificial muscles that can accomplish these actions simultaneously. We found that the single layered, latticed microstructure of onion epidermal cells after acid treatment became elastic and could simultaneously stretch and bend when an electric field was applied. By modulating the magnitude of the voltage, the artificial muscle made of onion epidermal cells would deflect in opposing directions while either contracting or elongating. At voltages of 0-50 V, the artificial muscle elongated and had a maximum deflection of -30 μm; at voltages of 50-1000 V, the artificial muscle contracted and deflected 1.0 mm. The maximum force response is 20 μN at 1000 V.

  17. Monitoring Murine Skeletal Muscle Function for Muscle Gene Therapy

    PubMed Central

    Hakim, Chady H.; Li, Dejia; Duan, Dongsheng

    2011-01-01

    The primary function of skeletal muscle is to generate force. Muscle force production is compromised in various forms of acquired and/or inherited muscle diseases. An important goal of muscle gene therapy is to recover muscle strength. Genetically engineered mice and spontaneous mouse mutants are readily available for preclinical muscle gene therapy studies. In this chapter, we outlined the methods commonly used for measuring murine skeletal muscle function. These include ex vivo and in situ analysis of the contractile profile of a single intact limb muscle (the extensor digitorium longus for ex vivo assay and the tibialis anterior muscle for in situ assay), grip force analysis, and downhill treadmill exercise. Force measurement in a single muscle is extremely useful for pilot testing of new gene therapy protocols by local gene transfer. Grip force and treadmill assessments offer body-wide evaluation following systemic muscle gene therapy. PMID:21194022

  18. Oral environment and cancer.

    PubMed

    Kudo, Yasusei; Tada, Hidesuke; Fujiwara, Natsumi; Tada, Yoshiko; Tsunematsu, Takaaki; Miyake, Yoichiro; Ishimaru, Naozumi

    2016-01-01

    Cancer is now the leading cause of death in Japan. A rapid increase in cancer mortality is expected as Japan is facing a super-aged society. Many causes of cancer are known to be closely linked to life style factors, such as smoking, drinking, and diet. The oral environment is known to be involved in the pathogenesis and development of various diseases such as bronchitis, pneumonia, diabetes, heart disease, and dementia. Because the oral cavity acts as the bodily entrance for air and food, it is constantly exposed to foreign substances, including bacteria and viruses. A large number of bacteria are endemic to the oral cavity, and indigenous oral flora act to prevent the settlement of foreign bacteria. The oral environment is influenced by local factors, including dental plaque, tartar, teeth alignment, occlusion, an incompatible prosthesis, and bad lifestyle habits, and systemic factors, including smoking, consumption of alcohol, irregular lifestyle and eating habits, obesity, stress, hormones, and heredity. It has recently been revealed that the oral environment is associated with cancer. In particular, commensal bacteria in the oral cavity are involved in the development of cancer. Moreover, Candida, human papilloma virus and Epstein-Barr virus as well as commensal bacteria have been reported to be associated with the pathogenesis of cancer. In this review, we introduce recent findings of the correlation between the oral environment and cancer. PMID:27482300

  19. Oral Transliterating. PEPNet Tipsheet

    ERIC Educational Resources Information Center

    Troiano, Claire A.

    2010-01-01

    An oral transliterator provides communication access to a person who is deaf or hard of hearing and who uses speechreading and speaking as a means of communicating. The oral transliterator, positioned in front of the speechreader, inaudibly repeats the spoken message, making it as speechreadable as possible. This is called Expressive Oral…

  20. Oral Transliterating. NETAC Tipsheet

    ERIC Educational Resources Information Center

    Troiano, Claire A.

    2005-01-01

    An oral transliterator provides communication access to a person who is deaf or hard of hearing and who uses speechreading and speaking as a means of communicating. The oral transliterator, positioned in front of the deaf person, inaudibly repeats the spoken message for the deaf person, making it as speechreadable as possible. This is called…

  1. Chronic exercise increases insulin binding in muscles but not liver

    SciTech Connect

    Bonen, A.; Clune, P.A.; Tan, M.H.

    1986-08-01

    It has been postulated that the improved glucose tolerance provoked by chronic exercise is primarily attributable to increased insulin binding in skeletal muscle. Therefore, the authors investigated the effects of progressively increased training (6 wk) on insulin binding by five hindlimb skeletal muscles and in liver. In the trained animals serum insulin levels at rest were lower either in a fed or fasted state and after an oral glucose tolerance test. Twenty-four hours after the last exercise bout sections of the liver, soleus (S), plantaris (P), extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG) muscles were pooled from four to six rats. Insulin binding to plasma membranes increased in S, P, and EDL but not in WG or in liver. There were insulin binding differences among muscles. Comparison of rank orders of insulin binding data with published glucose transport data for the same muscles revealed that these parameters do not correspond well. In conclusion, insulin binding to muscle is shown to be heterogeneous and training can increase insulin binding to selected muscles but not liver.

  2. Skeletal muscle mass is associated with severe dysphagia in cancer patients

    PubMed Central

    Wakabayashi, Hidetaka; Matsushima, Masato; Uwano, Rimiko; Watanabe, Naoko; Oritsu, Hideyuki; Shimizu, Yoshitaka

    2015-01-01

    Background The purpose of this study was to assess the association between skeletal muscle mass, activities of daily living (ADLs) and severe dysphagia in cancer patients. Methods A nested case-control study was performed in 111 consecutive cancer patients with dysphagia who were prescribed speech therapy. Skeletal muscle mass comprising the cross-sectional area of the left and right psoas muscles was assessed via abdominal computed tomography at the third lumbar vertebral level. ADLs were evaluated by the Barthel Index. The severity of dysphagia was assessed by the Food Intake Level Scale and was characterized by non-oral feeding or oral food intake at discharge. Univariate and logistic regression analyses were applied to examine the associations between dysphagia, skeletal muscle index (SMI) and ADLs. Results There were 86 men and 25 women (mean age, 70 years). The mean SMI was 5.68 ± 1.74 cm2/m2 in men and 4.43 ± 1.21 cm2/m2 in women. The median Barthel Index score was 20. Thirty-three patients were on non-oral feeding at discharge. The mean SMI did not differ significantly between non-oral feeding and oral food intake groups in t-test. The median Barthel Index score was lower in the non-oral feeding group in Mann–Whitney U test. Logistic regression analysis of the severity of dysphagia adjusted for age, sex, SMI, Barthel Index score, serum albumin, cancer type and stage, and vocal cord paralysis showed that SMI was associated independently with oral food intake at discharge. Barthel Index score showed a tendency to be associated with oral food intake. Conclusions Skeletal muscle mass is associated with severe dysphagia in cancer patients. ADLs show a tendency to be associated with severe dysphagia in cancer patients. PMID:26673551

  3. Curricular Guidelines for Oral Biology.

    ERIC Educational Resources Information Center

    Journal of Dental Education, 1984

    1984-01-01

    The American Association of Dental Schools' guidelines for oral biology curriculum cover its scope, primary educational goals, prerequisites, sequencing, faculty, course content in each subarea (oral tissues and systems and oral diagnostic methodology), and specific behavioral objectives. (MSE)

  4. Thrush (Oral Candidiasis) in Children

    MedlinePlus

    ... A A A In oral candidiasis, normal mouth yeast overgrows, causing white, slightly elevated lesions. Overview Thrush ( ... candidiasis), also known as oral moniliasis, is a yeast infection of the mouth or throat (the oral ...

  5. Oral Contraceptive Pill and PCOS

    MedlinePlus

    ... Health Gynecology Medical Conditions Nutrition & Fitness Emotional Health PCOS: The Oral Contraceptive Pill Posted under Health Guides . ... of oral contraceptive pills for young women with PCOS? Regular and Lighter Periods: Oral contraceptive pills can ...

  6. Literatura Oral Hispanica (Hispanic Oral Literature).

    ERIC Educational Resources Information Center

    McAlpine, Dave

    As part of a class in Hispanic Oral Literature, students collected pieces of folklore from various Hispanic residents in the region known as "Siouxland" in Iowa. Consisting of some of the folklore recorded from the residents, this paper includes 18 "cuentos y leyendas" (tales and legends), 48 "refranes" (proverbs), 17 "chistes" (jokes), 1…

  7. Respiratory Muscle Plasticity

    PubMed Central

    Gransee, Heather M.; Mantilla, Carlos B.; Sieck, Gary C.

    2014-01-01

    Muscle plasticity is defined as the ability of a given muscle to alter its structural and functional properties in accordance with the environmental conditions imposed on it. As such, respiratory muscle is in a constant state of remodeling, and the basis of muscle’s plasticity is its ability to change protein expression and resultant protein balance in response to varying environmental conditions. Here, we will describe the changes of respiratory muscle imposed by extrinsic changes in mechanical load, activity, and innervation. Although there is a large body of literature on the structural and functional plasticity of respiratory muscles, we are only beginning to understand the molecular-scale protein changes that contribute to protein balance. We will give an overview of key mechanisms regulating protein synthesis and protein degradation, as well as the complex interactions between them. We suggest future application of a systems biology approach that would develop a mathematical model of protein balance and greatly improve treatments in a variety of clinical settings related to maintaining both muscle mass and optimal contractile function of respiratory muscles. PMID:23798306

  8. Muscle regeneration after sepsis.

    PubMed

    Bouglé, Adrien; Rocheteau, Pierre; Sharshar, Tarek; Chrétien, Fabrice

    2016-01-01

    Severe critical illness is often complicated by intensive care unit-acquired weakness (ICU-AW), which is associated with increased ICU and post-ICU mortality, delayed weaning from mechanical ventilation and long-term functional disability. Several mechanisms have been implicated in the pathophysiology of ICU-AW, but muscle regeneration has not been investigated to any extent in this context, even though its involvement is suggested by the protracted functional consequences of ICU-AW. Recent data suggest that muscle regeneration could be impaired after sepsis, and that mesenchymal stem cell treatment could improve the post-injury muscle recovery. PMID:27193340

  9. Examining the association between oral health and oral HPV infection.

    PubMed

    Bui, Thanh Cong; Markham, Christine M; Ross, Michael Wallis; Mullen, Patricia Dolan

    2013-09-01

    Oral human papillomavirus (HPV) infection is the cause of 40% to 80% of oropharyngeal cancers; yet, no published study has examined the role of oral health in oral HPV infection, either independently or in conjunction with other risk factors. This study examined the relation between oral health and oral HPV infection and the interactive effects of oral health, smoking, and oral sex on oral HPV infection. Our analyses comprised 3,439 participants ages 30 to 69 years for whom data on oral HPV and oral health were available from the nationally representative 2009-2010 National Health and Nutrition Examination Survey. Results showed that higher unadjusted prevalence of oral HPV infection was associated with four measures of oral health, including self-rated oral health as poor-to-fair [prevalence ratio (PR) = 1.56; 95% confidence interval (CI), 1.25-1.95], indicated the possibility of gum disease (PR = 1.51; 95% CI, 1.13-2.01), reported use of mouthwash to treat dental problems in the past week (PR = 1.28; 95% CI, 1.07-1.52), and higher number of teeth lost (Ptrend = 0.035). In multivariable logistic regression models, oral HPV infection had a statistically significant association with self-rated overall oral health (OR = 1.55; 95% CI, 1.15-2.09), independent of smoking and oral sex. In conclusion, poor oral health was an independent risk factor of oral HPV infection, irrespective of smoking and oral sex practices. Public health interventions may aim to promote oral hygiene and oral health as an additional measure to prevent HPV-related oral cancers.

  10. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

    PubMed Central

    Kim, Joo Wan; Ku, Sae-Kwang; Kim, Ki Young; Kim, Sung Goo; Han, Min Ho; Kim, Gi-Young; Hwang, Hye Jin; Kim, Byung Woo; Kim, Cheol Min

    2015-01-01

    The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation. PMID:26064425

  11. Ibuprofen Ingestion Does Not Affect Markers of Post-exercise Muscle Inflammation

    PubMed Central

    Vella, Luke; Markworth, James F.; Paulsen, Gøran; Raastad, Truls; Peake, Jonathan M.; Snow, Rod J.; Cameron-Smith, David; Russell, Aaron P.

    2016-01-01

    Purpose: We investigated if oral ingestion of ibuprofen influenced leucocyte recruitment and infiltration following an acute bout of traditional resistance exercise Methods: Sixteen male subjects were divided into two groups that received the maximum over-the-counter dose of ibuprofen (1200mg d−1) or a similarly administered placebo following lower body resistance exercise. Muscle biopsies were taken from m.vastus lateralis and blood serum samples were obtained before and immediately after exercise, and at 3 and 24 h after exercise. Muscle cross-sections were stained with antibodies against neutrophils (CD66b and MPO) and macrophages (CD68). Muscle damage was assessed via creatine kinase and myoglobin in blood serum samples, and muscle soreness was rated on a ten-point pain scale. Results: The resistance exercise protocol stimulated a significant increase in the number of CD66b+ and MPO+ cells when measured 3 h post exercise. Serum creatine kinase, myoglobin and subjective muscle soreness all increased post-exercise. Muscle leucocyte infiltration, creatine kinase, myoglobin and subjective muscle soreness were unaffected by ibuprofen treatment when compared to placebo. There was also no association between increases in inflammatory leucocytes and any other marker of cellular muscle damage. Conclusion: Ibuprofen administration had no effect on the accumulation of neutrophils, markers of muscle damage or muscle soreness during the first 24 h of post-exercise muscle recovery. PMID:27064890

  12. The effect of food on the pharmacokinetics of oral fluralaner in dogs

    PubMed Central

    2014-01-01

    Background Fluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. The pharmacokinetics of orally administered drugs may be influenced by feeding. This study investigated the influence of concurrent feeding on fluralaner pharmacokinetics. Methods Twelve fasted or fed beagles received a single oral administration of 25 mg fluralaner/kg body weight in a chewable tablet. Plasma samples were collected at multiple post-treatment time points for fluralaner concentration analysis. Clinical observations were performed on all dogs at regular intervals throughout the study. Results Fluralaner was readily absorbed in fasted and fed dogs administered at a dose of 25 mg/kg BW with a similar mean tmax for both groups. In fed dogs, AUC and Cmax were increased compared to fasted dogs by a factor of 2.5 and 2.1 respectively. The difference in AUC and Cmax between the fed and fasted groups was statistically significant. No adverse events were observed following oral fluralaner administration to fasted and fed dogs. Conclusions Fluralaner is absorbed to a considerable extent in fasted and fed dogs. Administration of fluralaner chewable tablets with food significantly increases bioavailability. PMID:24598049

  13. Comparing Effectiveness of Active and Passive Client Follow-Up Approaches in Sustaining the Continued Use of Long Acting Reversible Contraceptives (LARC) in Rural Punjab: A Multicentre, Non-Inferiority Trial

    PubMed Central

    Hameed, Waqas; Azmat, Syed Khurram; Ali, Moazzam; Ishaque, Muhammad; Abbas, Ghazunfer; Munroe, Erik; Harrison, Rebecca; Shamsi, Wajahat Hussain; Mustafa, Ghulam; Khan, Omar Farooq; Ali, Safdar; Ahmed, Aftab

    2016-01-01

    Background The use of long-acting reversible contraceptive (LARC) methods is very low in Pakistan with high discontinuation rates mainly attributed to method-related side effects. Mixed evidence is available on the effectiveness of different client follow-up approaches used to ensure method continuation. We compared the effectiveness of active and passive follow-up approaches in sustaining the use of LARC—and within ‘active’ follow-up, we further compared a telephone versus home-based approach in rural Punjab, Pakistan. Methods This was a 12-month multicentre non-inferiority trial conducted in twenty-two (16 rural- and 6 urban-based) franchised reproductive healthcare facilities in district Chakwal of Punjab province, between November 2013 and December 2014. The study comprised of three groups of LARC clients: a) home-based follow-up, b) telephone-based follow-up, and c) passive or needs-based follow-up. Participants in the first two study groups received counselling on scheduled follow-up from the field workers at 1, 3, 6, 9, and 12 month post-insertion whereas participants in the third group were asked to contact the health facility if in need of medical assistance relating to LARC method use. Study participants were recruited with equal allocation to each study group, but participants were not randomized. The analyses are based on 1,246 LARC (intra-uterine contraceptive device and implant) users that completed approximately 12-months of follow-up. The non-inferiority margin was kept at five percentage points for the comparison of active and passive follow-up and six percentage points for telephone and home-based approach. The primary outcome was cumulative probability of method continuation at 12-month among LARC users. Results Women recruited in home-based, telephone-based, and passive groups were 400, 419 and 427, respectively. The cumulative probability of LARC continuation at 12 month was 87.6% (95% CI 83.8 to 90.6) among women who received home

  14. Etiology of oral habits.

    PubMed

    Bayardo, R E; Mejia, J J; Orozco, S; Montoya, K

    1996-01-01

    The pedodontic admission histories of 1600 Mexican children were analyzed, to determine general epidemiologic factors or oral habits, as well as their relationship with identifiable biopsychosociologic factors. Fifty-six percent of the children gave evidence of an oral habit, with significant predisposition among female patients, single children, subjects in poor physical health (particularly from allergies), as well as children with histories of chronic health problems. Oral habits should be considered a major health hazard because of their high incidence. Successful treatment requires a multidisciplinary approach to the basic cause of the problem.

  15. Oral Lesions in Neonates

    PubMed Central

    Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    ABSTRACT Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  16. Muscles of the Trunk

    MedlinePlus

    ... Home » Cancer Registration & Surveillance Modules » Anatomy & Physiology » Muscular System » Muscle Groups » Trunk Cancer Registration & Surveillance Modules Anatomy & Physiology Intro to the Human Body Body Functions & Life Process Anatomical Terminology Review Quiz ...

  17. Neurogenic muscle cramps.

    PubMed

    Katzberg, Hans D

    2015-08-01

    Muscle cramps are sustained, painful contractions of muscle and are prevalent in patients with and without medical conditions. The objective of this review is to present updates on the mechanism, investigation and treatment of neurogenic muscle cramps. PubMed and Embase databases were queried between January 1980 and July 2014 for English-language human studies. The American Academy of Neurology classification of studies (classes I-IV) was used to assess levels of evidence. Mechanical disruption, ephaptic transmission, disruption of sensory afferents and persistent inward currents have been implicated in the pathogenesis of neurogenic cramps. Investigations are directed toward identifying physiological triggers or medical conditions predisposing to cramps. Although cramps can be self-limiting, disabling or sustained muscle cramps should prompt investigation for underlying medical conditions. Lifestyle modifications, treatment of underlying conditions, stretching, B-complex vitamins, diltiezam, mexiletine, carbamazepine, tetrahydrocannabinoid, leveteracitam and quinine sulfate have shown evidence for treatment. PMID:25673127

  18. Muscle biopsy (image)

    MedlinePlus

    A muscle biopsy involves removal of a plug of tissue usually by a needle to be later used for examination. Sometimes ... there is a patchy condition expected an open biopsy may be used. Open biopsy involves a small ...

  19. Research opportunities in muscle atrophy

    NASA Technical Reports Server (NTRS)

    Herbison, G. J. (Editor); Talbot, J. M. (Editor)

    1984-01-01

    Muscle atrophy in a weightless environment is studied. Topics of investigation include physiological factors of muscle atrophy in space flight, biochemistry, countermeasures, modelling of atrophied muscle tissue, and various methods of measurement of muscle strength and endurance. A review of the current literature and suggestions for future research are included.

  20. Muscle Fiber Types and Training.

    ERIC Educational Resources Information Center

    Karp, Jason R.

    2001-01-01

    The specific types of fibers that make up individual muscles greatly influence how people will adapt to their training programs. This paper explains the complexities of skeletal muscles, focusing on types of muscle fibers (slow-twitch and fast-twitch), recruitment of muscle fibers to perform a motor task, and determining fiber type. Implications…

  1. An invertebrate smooth muscle with striated muscle myosin filaments

    PubMed Central

    Sulbarán, Guidenn; Alamo, Lorenzo; Pinto, Antonio; Márquez, Gustavo; Méndez, Franklin; Padrón, Raúl; Craig, Roger

    2015-01-01

    Muscle tissues are classically divided into two major types, depending on the presence or absence of striations. In striated muscles, the actin filaments are anchored at Z-lines and the myosin and actin filaments are in register, whereas in smooth muscles, the actin filaments are attached to dense bodies and the myosin and actin filaments are out of register. The structure of the filaments in smooth muscles is also different from that in striated muscles. Here we have studied the structure of myosin filaments from the smooth muscles of the human parasite Schistosoma mansoni. We find, surprisingly, that they are indistinguishable from those in an arthropod striated muscle. This structural similarity is supported by sequence comparison between the schistosome myosin II heavy chain and known striated muscle myosins. In contrast, the actin filaments of schistosomes are similar to those of smooth muscles, lacking troponin-dependent regulation. We conclude that schistosome muscles are hybrids, containing striated muscle-like myosin filaments and smooth muscle-like actin filaments in a smooth muscle architecture. This surprising finding has broad significance for understanding how muscles are built and how they evolved, and challenges the paradigm that smooth and striated muscles always have distinctly different components. PMID:26443857

  2. Bound potassium in muscle II.

    PubMed

    Hummel, Z

    1980-01-01

    Experiments were performed to decide between the alternatives a) the ionized K+ is in a dissolved state in the muscle water, or b) a part of the muscle potassium is in a "bound' state. Sartorius muscles of Rana esculenta were put into glicerol for about one hour at 0-2 degrees C. Most of muscle water came out, but most of muscle potassium remained in the muscles. In contrast to this: from muscle in heat rigor more potassium was released due to glicerol treating than from the intact ones. 1. Supposition a) is experimentally refuted. 2. Supposition b) corresponds to the experimental results. PMID:6969511

  3. OBLIQUELY STRIATED MUSCLE

    PubMed Central

    Rosenbluth, Jack

    1967-01-01

    Segments of the obliquely striated body muscle of Ascaris were fixed at minimum body length after treatment with acetylcholine and at maximum body length after treatment with piperazine citrate and then studied by light and electron microscopy. Evidence was found for two mechanisms of length change: sliding of thin filaments with respect to thick filaments such as occurs in cross-striated muscle, and shearing of thick filaments with respect to each other such that the degree of their stagger increases with extension and decreases with shortening. The shearing mechanism could account for great extensibility in this muscle and in nonstriated muscles in general and could underlie other manifestations of "plasticity" as well. In addition, it is suggested that the contractile apparatus is attached to the endomysium in such a way that the sarcomeres can act either in series, as in cross-striated muscle, or individually. Since the sarcomeres are virtually longitudinal in orientation and are almost coextensive with the muscle fiber, it would, therefore, be possible for a single sarcomere contracting independently to develop tension effectively between widely separated points on the fiber surface, thus permitting very efficient maintenance of isometric tension. PMID:6040534

  4. Head muscle development.

    PubMed

    Tzahor, Eldad

    2015-01-01

    The developmental paths that lead to the formation of skeletal muscles in the head are distinct from those operating in the trunk. Craniofacial muscles are associated with head and neck structures. In the embryo, these structures derive from distinct mesoderm populations. Distinct genetic programs regulate different groups of muscles within the head to generate diverse muscle specifications. Developmental and lineage studies in vertebrates and invertebrates demonstrated an overlap in progenitor populations derived from the pharyngeal mesoderm that contribute to certain head muscles and the heart. These studies reveal that the genetic program controlling pharyngeal muscles overlaps with that of the heart. Indeed cardiac and craniofacial birth defects are often linked. Recent studies suggest that early chordates, the last common ancestor of tunicates and vertebrates, had an ancestral pharyngeal mesoderm lineage that later during evolution gave rise to both heart and craniofacial structures. This chapter summarizes studies related to the origins, signaling, genetics, and evolution of the head musculature, highlighting its heterogeneous characteristics in all these aspects.

  5. Important role of muscle carnosine in rowing performance.

    PubMed

    Baguet, Audrey; Bourgois, Jan; Vanhee, Lander; Achten, Eric; Derave, Wim

    2010-10-01

    The role of the presence of carnosine (β-alanyl-L-histidine) in millimolar concentrations in human skeletal muscle is poorly understood. Chronic oral β-alanine supplementation is shown to elevate muscle carnosine content and improve anaerobic exercise performance during some laboratory tests, mainly in the untrained. It remains to be determined whether carnosine loading can improve single competition-like events in elite athletes. The aims of the present study were to investigate if performance is related to the muscle carnosine content and if β-alanine supplementation improves performance in highly trained rowers. Eighteen Belgian elite rowers were supplemented for 7 wk with either placebo or β-alanine (5 g/day). Before and following supplementation, muscle carnosine content in soleus and gastrocnemius medialis was measured by proton magnetic resonance spectroscopy ((1)H-MRS) and the performance was evaluated in a 2,000-m ergometer test. At baseline, there was a strong positive correlation between 100-, 500-, 2,000-, and 6,000-m speed and muscle carnosine content. After β-alanine supplementation, the carnosine content increased by 45.3% in soleus and 28.2% in gastrocnemius. Following supplementation, the β-alanine group was 4.3 s faster than the placebo group, whereas before supplementation they were 0.3 s slower (P = 0.07). Muscle carnosine elevation was positively correlated to 2,000-m performance enhancement (P = 0.042 and r = 0.498). It can be concluded that the positive correlation between baseline muscle carnosine levels and rowing performance and the positive correlation between changes in muscle carnosine and performance improvement suggest that muscle carnosine is a new determinant of rowing performance. PMID:20671038

  6. Hypophosphatemia promotes lower rates of muscle ATP synthesis

    PubMed Central

    Pesta, Dominik H.; Tsirigotis, Dimitrios N.; Befroy, Douglas E.; Caballero, Daniel; Jurczak, Michael J.; Rahimi, Yasmeen; Cline, Gary W.; Dufour, Sylvie; Birkenfeld, Andreas L.; Rothman, Douglas L.; Carpenter, Thomas O.; Insogna, Karl; Petersen, Kitt Falk; Bergwitz, Clemens; Shulman, Gerald I.

    2016-01-01

    Hypophosphatemia can lead to muscle weakness and respiratory and heart failure, but the mechanism is unknown. To address this question, we noninvasively assessed rates of muscle ATP synthesis in hypophosphatemic mice by using in vivo saturation transfer [31P]-magnetic resonance spectroscopy. By using this approach, we found that basal and insulin-stimulated rates of muscle ATP synthetic flux (VATP) and plasma inorganic phosphate (Pi) were reduced by 50% in mice with diet-induced hypophosphatemia as well as in sodium-dependent Pi transporter solute carrier family 34, member 1 (NaPi2a)-knockout (NaPi2a−/−) mice compared with their wild-type littermate controls. Rates of VATP normalized in both hypophosphatemic groups after restoring plasma Pi concentrations. Furthermore, VATP was directly related to cellular and mitochondrial Pi uptake in L6 and RC13 rodent myocytes and isolated muscle mitochondria. Similar findings were observed in a patient with chronic hypophosphatemia as a result of a mutation in SLC34A3 who had a 50% reduction in both serum Pi content and muscle VATP. After oral Pi repletion and normalization of serum Pi levels, muscle VATP completely normalized in the patient. Taken together, these data support the hypothesis that decreased muscle ATP synthesis, in part, may be caused by low blood Pi concentrations, which may explain some aspects of muscle weakness observed in patients with hypophosphatemia.—Pesta, D. H., Tsirigotis, D. N., Befroy, D. E., Caballero, D., Jurczak, M. J., Rahimi, Y., Cline, G. W., Dufour, S., Birkenfeld, A. L., Rothman, D. L., Carpenter, T. O., Insogna, K., Petersen, K. F., Bergwitz, C., Shulman, G. I. Hypophosphatemia promotes lower rates of muscle ATP synthesis. PMID:27338702

  7. Oral sex and oral health: An enigma in itself.

    PubMed

    Kumar, Tarun; Puri, Gagan; Aravinda, Konidena; Arora, Neha; Patil, Deepa; Gupta, Rajesh

    2015-01-01

    Oral sex is commonly practiced by sexually active couples of various age groups, including male-female and same-gender adolescents. The various type of oral sex practices are fellatio, cunnilingus, and analingus. Oral sex can transmit oral, respiratory, and genital infections from one site in body to the other. Oral health has a direct correlation on the transmission of infection; a cut in the mouth, bleeding gums, lip sores or broken skin increases chances of life-threatening infections. Although oral sex is considered a low risk activity, it is important to use protection such as physical barriers, health and medical issues, ethical issues, and oral hygiene and dental issues. The ulcerations or unhealthy periodontium in mouth accelerates the phenomenon of transmission of infections into the circulation. Thus, consequences of unhealthy or painful oral cavity are significant and oral health should be given paramount importance for the practice of oral sex. PMID:26692602

  8. Oral sex and oral health: An enigma in itself.

    PubMed

    Kumar, Tarun; Puri, Gagan; Aravinda, Konidena; Arora, Neha; Patil, Deepa; Gupta, Rajesh

    2015-01-01

    Oral sex is commonly practiced by sexually active couples of various age groups, including male-female and same-gender adolescents. The various type of oral sex practices are fellatio, cunnilingus, and analingus. Oral sex can transmit oral, respiratory, and genital infections from one site in body to the other. Oral health has a direct correlation on the transmission of infection; a cut in the mouth, bleeding gums, lip sores or broken skin increases chances of life-threatening infections. Although oral sex is considered a low risk activity, it is important to use protection such as physical barriers, health and medical issues, ethical issues, and oral hygiene and dental issues. The ulcerations or unhealthy periodontium in mouth accelerates the phenomenon of transmission of infections into the circulation. Thus, consequences of unhealthy or painful oral cavity are significant and oral health should be given paramount importance for the practice of oral sex.

  9. Oral Cancer Exam

    MedlinePlus

    ... Diabetes Heart Disease HIV/AIDS See All Order Publications English and Spanish brochures available free of charge. ... early—when it can be treated more successfully. Publications​ For Health Professionals Detecting Oral Cancer: A Guide ...

  10. Oral Cancer Foundation

    MedlinePlus

    ... Oral Cancer Foundation is a national public service, non-profit entity designed to reduce suffering and save lives ... National Academy of Sciences (NAS) is a private, non-profit society of distinguished scholars. Established by an Act ...

  11. Olodaterol Oral Inhalation

    MedlinePlus

    ... of breath, coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways, which includes chronic bronchitis and emphysema). Olodaterol oral inhalation is in ...

  12. Oral hypoglycemics overdose

    MedlinePlus

    ... calling the national toll-free Poison Help hotline (1-800-222-1222) from anywhere in the United States. Poisonous Ingredient There are many types of oral hypoglycemics. The poisonous ingredient depends on ...

  13. Budesonide Oral Inhalation

    MedlinePlus

    ... 6 years of age and older. Budesonide suspension (liquid) for oral inhalation (Pulmicort Respules) is used in ... of inhalations even if it still contains some liquid and continues to release a spray when it ...

  14. Oral pigmentation: A review

    PubMed Central

    Sreeja, C.; Ramakrishnan, K.; Vijayalakshmi, D.; Devi, M.; Aesha, I.; Vijayabanu, B.

    2015-01-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID:26538887

  15. Oral vs. salivary diagnostics

    NASA Astrophysics Data System (ADS)

    Marques, Joana; Corby, Patricia M.; Barber, Cheryl A.; Abrams, William R.; Malamud, Daniel

    2015-05-01

    The field of "salivary diagnostics" includes studies utilizing samples obtained from a variety of sources within the oral cavity. These samples include; whole unstimulated saliva, stimulated whole saliva, duct saliva collected directly from the parotid, submandibular/sublingual glands or minor salivary glands, swabs of the buccal mucosa, tongue or tonsils, and gingival crevicular fluid. Many publications state "we collected saliva from subjects" without fully describing the process or source of the oral fluid. Factors that need to be documented in any study include the time of day of the collection, the method used to stimulate and collect the fluid, and how much fluid is being collected and for how long. The handling of the oral fluid during and post-collection is also critical and may include addition of protease or nuclease inhibitors, centrifugation, and cold or frozen storage prior to assay. In an effort to create a standard protocol for determining a biomarker's origin we carried out a pilot study collecting oral fluid from 5 different sites in the mouth and monitoring the concentrations of pro- and anti-inflammatory cytokines detected using MesoScaleDiscovery (MSD) electrochemiluminesence assays. Our data suggested that 3 of the cytokines are primarily derived from the submandibular gland, while 7 of the cytokines come from a source other than the major salivary glands such as the minor salivary glands or cells in the oral mucosae. Here we review the literature on monitoring biomarkers in oral samples and stress the need for determining the blood/saliva ratio when a quantitative determination is needed and suggest that the term oral diagnostic be used if the source of an analyte in the oral cavity is unknown.

  16. Oral pigmentation: A review.

    PubMed

    Sreeja, C; Ramakrishnan, K; Vijayalakshmi, D; Devi, M; Aesha, I; Vijayabanu, B

    2015-08-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID:26538887

  17. Muscle hardness characteristics of the masseter muscle after repetitive muscle activation: comparison to the biceps brachii muscle.

    PubMed

    Kashima, Koji; Higashinaka, Shuichi; Watanabe, Naoshi; Maeda, Sho; Shiba, Ryosuke

    2004-10-01

    The purpose of this study was to compare hardness characteristics of the masseter muscle to those of the biceps brachii muscle during repetitive muscle movements. Seventeen asymptomatic female subjects participated in this study. Each subject, on separate days, undertook a 5-minute unilateral chewing gum task on the right side and a 5-minute flexion-extension exercise on the right hand with a 2kg dumbbell. Using a handheld hardness meter, muscle hardness was measured in the right masseter and in the biceps brachii muscle at eight time points (before the task, immediately after the task, and at 1, 3, 5, 10, 30, and 60 minutes after the task), and the data obtained before and after the task on each muscle were compared. Comparisons of the normalized data were also performed between the two muscles at each time point. As a result, a significant increase in muscle hardness was seen at 1 minute after the task in the biceps brachii muscle (p=0.0093). In contrast, the masseter muscle showed a tendency to lower hardness, with the lowest point of hardness occurring at 10 minutes after the task (p = 0.0160). Between the two muscles, there was a difference in the normalized data immediately after the task, and at 1, 5, and 10 minutes after the task (0.01 muscle hardness characteristics of the masseter muscle completely differed from those of the biceps brachii muscle after repetitive muscle activation.

  18. Oral and systemic photoprotection.

    PubMed

    Chen, Andrew C; Damian, Diona L; Halliday, Gary M

    2014-01-01

    Photoprotection can be provided not only by ultraviolet (UV) blockers but also by oral substances. Epidemiologically identified associations between foods and skin cancer and interventional experiments have discovered mechanisms of UV skin damage. These approaches have identified oral substances that are photoprotective in humans. UV inhibits adenosine triphosphate (ATP) production causing an energy crisis, which prevents optimal skin immunity and DNA repair. Enhancing ATP production with oral nicotinamide protects from UV immunosuppression, enhances DNA repair and reduces skin cancer in humans. Reactive oxygen species also contribute to photodamage. Nontoxic substances consumed in the diet, or available as oral supplements, can protect the skin by multiple potential mechanisms. These substances include polyphenols in fruit, vegetables, wine, tea and caffeine-containing foods. UV-induced prostaglandin E2 (PGE2 ) contributes to photodamage. Nonsteroidal anti-inflammatory drugs and food substances reduce production of this lipid mediator. Fish oils are photoprotective, at least partially by reducing PGE2 . Orally consumed substances, either in the diet or as supplements, can influence cutaneous responses to UV. A current research goal is to develop an oral supplement that could be used in conjunction with other sun protective strategies in order to provide improved protection from sunlight.

  19. Personality and oral health

    PubMed Central

    Thomson, W. Murray; Caspi, Avshalom; Poulton, Richie; Moffitt, Terrie E.; Broadbent, Jonathan M.

    2013-01-01

    We investigated age-26 personality characteristics and age-32 oral health in a prospective study of a complete birth cohort born in Dunedin, New Zealand. Personality was measured using the Multidimensional Personality Questionnaire (MPQ). Oral health was measured using the short-form Oral Health Impact Profile (OHIP-14), a global measure, and dental examinations. Personality profiles were constructed for 916 individuals (50.8% men) using standardized MPQ scores, and multivariate analyses examined their association with oral health. Those reporting 1+ OHIP-14 impacts had higher Negative Emotionality scores (and lower Constraint and Positive Emotionality MPQ superfactor scores) than those who did not. After controlling for gender, clinical status, and the other two MPQ superfactors, those scoring higher on Negative Emotionality had a greater risk of reporting 1+ OHIP-14 impacts, as well as 3+ OHIP-14 impacts and worse-than-average oral health. They also had a greater risk of having lost at least one tooth from caries and of having 3+ decayed surfaces. Personality characteristics appear to shape self-reports of oral health. Personality is also a risk factor for clinical disease status, at least with respect to dental caries and its sequelae. Because the attitudes and values tapped into by personality tests can be altered by brief cognitive interventions, those might be useful in preventive dentistry. PMID:21896053

  20. Oral and systemic photoprotection.

    PubMed

    Chen, Andrew C; Damian, Diona L; Halliday, Gary M

    2014-01-01

    Photoprotection can be provided not only by ultraviolet (UV) blockers but also by oral substances. Epidemiologically identified associations between foods and skin cancer and interventional experiments have discovered mechanisms of UV skin damage. These approaches have identified oral substances that are photoprotective in humans. UV inhibits adenosine triphosphate (ATP) production causing an energy crisis, which prevents optimal skin immunity and DNA repair. Enhancing ATP production with oral nicotinamide protects from UV immunosuppression, enhances DNA repair and reduces skin cancer in humans. Reactive oxygen species also contribute to photodamage. Nontoxic substances consumed in the diet, or available as oral supplements, can protect the skin by multiple potential mechanisms. These substances include polyphenols in fruit, vegetables, wine, tea and caffeine-containing foods. UV-induced prostaglandin E2 (PGE2 ) contributes to photodamage. Nonsteroidal anti-inflammatory drugs and food substances reduce production of this lipid mediator. Fish oils are photoprotective, at least partially by reducing PGE2 . Orally consumed substances, either in the diet or as supplements, can influence cutaneous responses to UV. A current research goal is to develop an oral supplement that could be used in conjunction with other sun protective strategies in order to provide improved protection from sunlight. PMID:24313740

  1. [Dementia and oral health].

    PubMed

    Wierink, C D; de Baat, C

    2009-02-01

    The first part of this article is a translation of an editorial which appeared in the journal Gerodontology. The author warns that a great increase is expected in the number of dementia patients in the United Kingdom and he argues that care for these patients be given a high place on the national agenda. Dementia was also a major issue at the meeting of the International Association for Dental Research in March 2007. Several international studies presented there indicated that elderly people with dementia constitute a group at risk with respect to oral health. In the evaluation of the editorial, the situation in The Netherlands is described. There is also serious concern in The Netherlands about the statistics with respect to dementia. Due to the growing number of frail elderly people having a natural dentition, the need for professional oral care will increase. General practitioners have the important task of providing adequate oral health care for elderly people suffering from dementia who are still living at home. Guidelines for Oral Care, having to do with the improvement of oral care in institutions, appeared recently. With the guidelines, a good basis for developing adequate oral health care of frail elderly people is available. However, the implementation of these guidelines will require some attention. PMID:19280891

  2. Personality and oral health.

    PubMed

    Thomson, W Murray; Caspi, Avshalom; Poulton, Richie; Moffitt, Terrie E; Broadbent, Jonathan M

    2011-10-01

    We investigated age-26 personality characteristics and age-32 oral health in a prospective study of a complete birth cohort born in Dunedin, New Zealand. Personality was measured using the Multidimensional Personality Questionnaire (MPQ). Oral health was measured using the short-form Oral Health Impact Profile (OHIP-14), a global measure, and dental examinations. Personality profiles were constructed for 916 individuals (50.8% men) using standardized MPQ scores, and multivariate analyses examined their association with oral health. Those reporting 1+ OHIP-14 impacts had higher Negative Emotionality scores (and lower Constraint and Positive Emotionality MPQ superfactor scores) than those who did not. After controlling for gender, clinical status, and the other two MPQ superfactors, those scoring higher on Negative Emotionality had a greater risk of reporting 1+ OHIP-14 impacts, as well as 3+ OHIP-14 impacts and worse-than-average oral health. They also had a greater risk of having lost at least one tooth from caries and of having 3+ decayed surfaces. Personality characteristics appear to shape self-reports of oral health. Personality is also a risk factor for clinical disease status, at least with respect to dental caries and its sequelae. Because the attitudes and values tapped into by personality tests can be altered by brief cognitive interventions, those might be useful in preventive dentistry.

  3. Melatonin and Oral Cavity

    PubMed Central

    Cengiz, Murat İnanç; Cengiz, Seda; Wang, Hom-Lay

    2012-01-01

    While initially the oral cavity was considered to be mainly a source of various bacteria, their toxins and antigens, recent studies showed that it may also be a location of oxidative stress and periodontal inflammation. Accordingly, this paper focuses on the involvement of melatonin in oxidative stress diseases of oral cavity as well as on potential therapeutic implications of melatonin in dental disorders. Melatonin has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue, and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a coadjuvant in the treatment of certain conditions of the oral cavity. However, the most important effect of melatonin seems to result from its potent antioxidant, immunomodulatory, protective, and anticancer properties. Thus, melatonin could be used therapeutically for instance, locally, in the oral cavity damage of mechanical, bacterial, fungal, or viral origin, in postsurgical wounds caused by tooth extractions and other oral surgeries. Additionally, it can help bone formation in various autoimmunological disorders such as Sjorgen syndrome, in periodontal diseases, in toxic effects of dental materials, in dental implants, and in oral cancers. PMID:22792106

  4. Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

    NASA Technical Reports Server (NTRS)

    Max, Stephen R.; Konagaya, Masaaki; Konagaya, Yoko; Thomas, John W.; Banner, Carl; Vitkovic, Ljubisa

    1986-01-01

    The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy.

  5. Time-frequency analysis of rhythmic masticatory muscle activity.

    PubMed

    Farella, Mauro; Palla, Sandro; Gallo, Luigi Maria

    2009-06-01

    The aim of this study was to develop and validate under laboratory conditions an algorithm for a time-frequency analysis of rhythmic masticatory muscle activity (RMMA). The algorithm baseband demodulated the electromyographic (EMG) signal to provide a frequency versus time representation. Using appropriate thresholds for frequency and power parameters, it was possible to automatically assess the features of RMMA without examiner interaction. The algorithm was first tested using synthetic EMG signals and then using real EMG signals obtained from the masticatory muscles of 11 human subjects who underwent well-defined rhythmic, static, and possible confounding oral tasks. The accuracy of detection was quantified by receiver operating characteristics (ROC) curves. Sensitivity and specificity values were > or =90% and > or =96%, respectively. The areas under the ROC curves were > or =95% (standard error +/-0.1%). The proposed approach represents a promising tool to effectively investigate rhythmical contractions of the masticatory muscles.

  6. Muscle wasting in cancer.

    PubMed

    Johns, N; Stephens, N A; Fearon, K C H

    2013-10-01

    Skeletal muscle loss appears to be the most significant clinical event in cancer cachexia and is associated with a poor outcome. With regard to such muscle loss, despite extensive study in a range of models, there is ongoing debate as to whether a reduction in protein synthesis, an increase in degradation or a combination of both is the more relevant. Each model differs in terms of key mediators and the pathways activated in skeletal muscle. Certain models do suggest that decreased synthesis accompanied by enhanced protein degradation via the ubiquitin proteasome pathway (UPP) is important. Murine models tend to involve rapid development of cachexia and may represent more acute muscle atrophy rather than the chronic wasting observed in humans. There is a paucity of human data both at a basic descriptive level and at a molecular/mechanism level. Progress in treating the human form of cancer cachexia can only move forwards through carefully designed large randomised controlled clinical trials of specific therapies with validated biomarkers of relevance to underlying mechanisms. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

  7. Muscle Injuries in Athletes

    PubMed Central

    Delos, Demetris; Maak, Travis G.; Rodeo, Scott A.

    2013-01-01

    Context: Muscle injuries are extremely common in athletes and often produce pain, dysfunction, and the inability to return to practice or competition. Appropriate diagnosis and management can optimize recovery and minimize time to return to play. Evidence Acquisition: Contemporary papers, both basic science and clinical medicine, that investigate muscle healing were reviewed. A Medline/PubMed search inclusive of years 1948 to 2012 was performed. Results: Diagnosis can usually be made according to history and physical examination for most injuries. Although data are limited, initial conservative management emphasizing the RICE principles and immobilization of the extremity for several days for higher grade injuries are typically all that is required. Injection of corticosteroids may clinically enhance function after an acute muscle strain. Additional adjunctive treatments (nonsteroidal anti-inflammatory drugs, platelet-rich plasma, and others) to enhance muscle healing and limit scar formation show promise but need additional data to better define their roles. Conclusion: Conservative treatment recommendations will typically lead to successful outcomes after a muscle injury. There is limited evidence to support most adjunctive treatments. PMID:24459552

  8. Positronium Formation in Muscle

    PubMed Central

    Gustafson, D. R.

    1970-01-01

    Positronium formation in muscle at +4°C and -4°C was examined by the measurement of the angular correlation of positron annihilation radiation. Since the positronium formation rate in ice is considerably higher than it is in water, there should be a comparable increase in the positronium formation rate in muscle tissue if recent speculation that cellular water is ordered in a semicrystalline icelike state is correct. Comparison of the angular correlation from muscle at +4°C with that from water at +4°C shows no enhancement of the positronium formation rate. Frozen muscle at -4°C shows an enhancement of the positronium formation rate of approximately half that found in ice at -4°C, indicating that most cellular water undergoes a normal water-ice transition when frozen. It is concluded therefore that cell water in muscle is not ordered in a hexagonal icelike structure. While the results are consistent with the hypothesis that cell water is in the liquid state, the hypothesis that cell water is ordered in an undetermined close packed structure which transforms to the hexagonal ice structure at or near 0°C cannot be ruled out. PMID:5436881

  9. A Beetle Flight Muscle Displays Leg Muscle Microstructure.

    PubMed

    Shimomura, Toshiki; Iwamoto, Hiroyuki; Vo Doan, Tat Thang; Ishiwata, Shin'ichi; Sato, Hirotaka; Suzuki, Madoka

    2016-09-20

    In contrast to major flight muscles in the Mecynorrhina torquata beetle, the third axillary (3Ax) muscle is a minor flight muscle that uniquely displays a powerful mechanical function despite its considerably small volume, ∼1/50 that of a major flight muscle. The 3Ax muscle contracts relatively slowly, and in flight strongly pulls the beating wing to attenuate the stroke amplitude. This attenuation leads to left-right turning in flight or wing folding to cease flying. What enables this small muscle to be so powerful? To explore this question, we examined the microstructure of the 3Ax muscle using synchrotron x-ray diffraction, optical microscopy, and immunoblotting analysis. We found that the 3Ax muscle has long (∼5 μm) myofilaments and that the ratio of thick (myosin) filaments to thin (actin) filaments is 1:5 or 1:6. These characteristics are not observed in the major flight muscles, which have shorter myofilaments (∼3.5 μm) with a smaller ratio (1:3), and instead are more typical of a leg muscle. Furthermore, the flight-muscle-specific troponin isoform, TnH, is not expressed in the 3Ax muscle. Since such a microstructure is suitable for generating large tension, the 3Ax muscle is appropriately designed to pull the wing strongly despite its small volume. PMID:27653488

  10. A Beetle Flight Muscle Displays Leg Muscle Microstructure.

    PubMed

    Shimomura, Toshiki; Iwamoto, Hiroyuki; Vo Doan, Tat Thang; Ishiwata, Shin'ichi; Sato, Hirotaka; Suzuki, Madoka

    2016-09-20

    In contrast to major flight muscles in the Mecynorrhina torquata beetle, the third axillary (3Ax) muscle is a minor flight muscle that uniquely displays a powerful mechanical function despite its considerably small volume, ∼1/50 that of a major flight muscle. The 3Ax muscle contracts relatively slowly, and in flight strongly pulls the beating wing to attenuate the stroke amplitude. This attenuation leads to left-right turning in flight or wing folding to cease flying. What enables this small muscle to be so powerful? To explore this question, we examined the microstructure of the 3Ax muscle using synchrotron x-ray diffraction, optical microscopy, and immunoblotting analysis. We found that the 3Ax muscle has long (∼5 μm) myofilaments and that the ratio of thick (myosin) filaments to thin (actin) filaments is 1:5 or 1:6. These characteristics are not observed in the major flight muscles, which have shorter myofilaments (∼3.5 μm) with a smaller ratio (1:3), and instead are more typical of a leg muscle. Furthermore, the flight-muscle-specific troponin isoform, TnH, is not expressed in the 3Ax muscle. Since such a microstructure is suitable for generating large tension, the 3Ax muscle is appropriately designed to pull the wing strongly despite its small volume.

  11. Artificial muscles on heat

    NASA Astrophysics Data System (ADS)

    McKay, Thomas G.; Shin, Dong Ki; Percy, Steven; Knight, Chris; McGarry, Scott; Anderson, Iain A.

    2014-03-01

    Many devices and processes produce low grade waste heat. Some of these include combustion engines, electrical circuits, biological processes and industrial processes. To harvest this heat energy thermoelectric devices, using the Seebeck effect, are commonly used. However, these devices have limitations in efficiency, and usable voltage. This paper investigates the viability of a Stirling engine coupled to an artificial muscle energy harvester to efficiently convert heat energy into electrical energy. The results present the testing of the prototype generator which produced 200 μW when operating at 75°C. Pathways for improved performance are discussed which include optimising the electronic control of the artificial muscle, adjusting the mechanical properties of the artificial muscle to work optimally with the remainder of the system, good sealing, and tuning the resonance of the displacer to minimise the power required to drive it.

  12. Signaling in muscle contraction.

    PubMed

    Kuo, Ivana Y; Ehrlich, Barbara E

    2015-02-02

    Signaling pathways regulate contraction of striated (skeletal and cardiac) and smooth muscle. Although these are similar, there are striking differences in the pathways that can be attributed to the distinct functional roles of the different muscle types. Muscles contract in response to depolarization, activation of G-protein-coupled receptors and other stimuli. The actomyosin fibers responsible for contraction require an increase in the cytosolic levels of calcium, which signaling pathways induce by promoting influx from extracellular sources or release from intracellular stores. Rises in cytosolic calcium stimulate numerous downstream calcium-dependent signaling pathways, which can also regulate contraction. Alterations to the signaling pathways that initiate and sustain contraction and relaxation occur as a consequence of exercise and pathophysiological conditions.

  13. Communication among Oral Bacteria

    PubMed Central

    Kolenbrander, Paul E.; Andersen, Roxanna N.; Blehert, David S.; Egland, Paul G.; Foster, Jamie S.; Palmer, Robert J.

    2002-01-01

    Human oral bacteria interact with their environment by attaching to surfaces and establishing mixed-species communities. As each bacterial cell attaches, it forms a new surface to which other cells can adhere. Adherence and community development are spatiotemporal; such order requires communication. The discovery of soluble signals, such as autoinducer-2, that may be exchanged within multispecies communities to convey information between organisms has emerged as a new research direction. Direct-contact signals, such as adhesins and receptors, that elicit changes in gene expression after cell-cell contact and biofilm growth are also an active research area. Considering that the majority of oral bacteria are organized in dense three-dimensional biofilms on teeth, confocal microscopy and fluorescently labeled probes provide valuable approaches for investigating the architecture of these organized communities in situ. Oral biofilms are readily accessible to microbiologists and are excellent model systems for studies of microbial communication. One attractive model system is a saliva-coated flowcell with oral bacterial biofilms growing on saliva as the sole nutrient source; an intergeneric mutualism is discussed. Several oral bacterial species are amenable to genetic manipulation for molecular characterization of communication both among bacteria and between bacteria and the host. A successful search for genes critical for mixed-species community organization will be accomplished only when it is conducted with mixed-species communities. PMID:12209001

  14. Oral Insulin Reloaded

    PubMed Central

    Heinemann, Lutz; Plum-Mörschel, Leona

    2014-01-01

    Optimal coverage of insulin needs is the paramount aim of insulin replacement therapy in patients with diabetes mellitus. To apply insulin without breaking the skin barrier by a needle and/or to allow a more physiological provision of insulin are the main reasons triggering the continuous search for alternative routes of insulin administration. Despite numerous attempts over the past 9 decades to develop an insulin pill, no insulin for oral dosing is commercially available. By way of a structured approach, we aim to provide a systematic update on the most recent developments toward an orally available insulin formulation with a clear focus on data from clinical-experimental and clinical studies. Thirteen companies that claim to be working on oral insulin formulations were identified. However, only 6 of these companies published new clinical trial results within the past 5 years. Interestingly, these clinical data reports make up a mere 4% of the considerably high total number of publications on the development of oral insulin formulations within this time period. While this picture clearly reflects the rising research interest in orally bioavailable insulin formulations, it also highlights the fact that the lion’s share of research efforts is still allocated to the preclinical stages. PMID:24876606

  15. The Oral Microbiota.

    PubMed

    Arweiler, Nicole B; Netuschil, Lutz

    2016-01-01

    The oral microbiota represents an important part of the human microbiota, and includes several hundred to several thousand diverse species. It is a normal part of the oral cavity and has an important function to protect against colonization of extrinsic bacteria which could affect systemic health. On the other hand, the most common oral diseases caries, gingivitis and periodontitis are based on microorganisms. While (medical) research focused on the planktonic phase of bacteria over the last 100 years, it is nowadays generally known, that oral microorganisms are organised as biofilms. On any non-shedding surfaces of the oral cavity dental plaque starts to form, which meets all criteria for a microbial biofilm and is subject to the so-called succession. When the sensitive ecosystem turns out of balance - either by overload or weak immune system - it becomes a challenge for local or systemic health. Therefore, the most common strategy and the golden standard for the prevention of caries, gingivitis and periodontitis is the mechanical removal of this biofilms from teeth, restorations or dental prosthesis by regular toothbrushing. PMID:27161350

  16. The Oral Microbiota.

    PubMed

    Arweiler, Nicole B; Netuschil, Lutz

    2016-01-01

    The oral microbiota represents an important part of the human microbiota, and includes several hundred to several thousand diverse species. It is a normal part of the oral cavity and has an important function to protect against colonization of extrinsic bacteria which could affect systemic health. On the other hand, the most common oral diseases caries, gingivitis and periodontitis are based on microorganisms. While (medical) research focused on the planktonic phase of bacteria over the last 100 years, it is nowadays generally known, that oral microorganisms are organised as biofilms. On any non-shedding surfaces of the oral cavity dental plaque starts to form, which meets all criteria for a microbial biofilm and is subject to the so-called succession. When the sensitive ecosystem turns out of balance - either by overload or weak immune system - it becomes a challenge for local or systemic health. Therefore, the most common strategy and the golden standard for the prevention of caries, gingivitis and periodontitis is the mechanical removal of this biofilms from teeth, restorations or dental prosthesis by regular toothbrushing.

  17. Orally administered grass pollen.

    PubMed

    Taudorf, E; Weeke, B

    1983-11-01

    In 1900 it was claimed that oral administration of ragweed could be used for the hyposensitization of hay fever patients. Several uncontrolled trials have been published, all showing an effect of oral hyposensitization. Only one study was controlled and showed no effect of oral hyposensitization. It was decided to undertake controlled clinical trials to determine the safety and effectiveness of orally administered enteric-coated grass pollen tablets in patients with hay fever. The actual grass pollen dose in the first trial was 30 times the dose that is normally recommended for preseasonal oral pollen hyposensitization using pollen aqueous solution or pollen powder. The safety study will be described here. Twelve young adults with a history of grass pollen hay fever positive skin prick test and positive nasal provocation test with extracts of timothy grass pollen were randomly allocated to one of the treatment groups with four patients in each group taking enteric-coated Conjuvac Timothy tablets or enteric-coated Whole Timothy pollen tablets or enteric-coated placebo tablets. The study was double blind. Preseasonally, the patients received 342,500 PNU and in total they received 4,500,000 PNU during 6 months. The patients receiving active treatment did not have any side effects. No significant changes were shown in the skin and nasal reactivity to grass pollen during the study. Neither were there any changes in timothy-specific IgE, IgG, total IgE nor histamine liberation from basophils.

  18. Substrate kinetics in patients with disorders of skeletal muscle metabolism