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Sample records for ongoing pharmacological treatment

  1. Pharmacologic treatment of paraphilias.

    PubMed

    Assumpção, Alessandra Almeida; Garcia, Frederico Duarte; Garcia, Heloise Delavenne; Bradford, John M W; Thibaut, Florence

    2014-06-01

    The treatment of paraphilias remains a challenge in the mental health field. Combined pharmacologic and psychotherapeutic treatment is associated with better efficacy. The gold standard treatment of severe paraphilias in adult males is antiandrogen treatment with cognitive behavioral therapy. Selective serotonin reuptake inhibitors have been used in mild types of paraphilia and in cases of sexual compulsions and juvenile paraphilias. Antiandrogen treatments seem to be effective in severe paraphilic subjects committing sexual offenses. In particular, gonadotropin-releasing hormone analogs have shown high efficacy working in a similar way to physical castration but being reversible at any time. Treatment recommendations, side effects, and contraindications are discussed. PMID:24877704

  2. Pharmacological treatment of vertigo.

    PubMed

    Hain, Timothy C; Uddin, Mohammed

    2003-01-01

    This review discusses the physiology and pharmacological treatment of vertigo and related disorders. Classes of medications useful in the treatment of vertigo include anticholinergics, antihistamines, benzodiazepines, calcium channel antagonists and dopamine receptor antagonists. These medications often have multiple actions. They may modify the intensity of symptoms (e.g. vestibular suppressants) or they may affect the underlying disease process (e.g. calcium channel antagonists in the case of vestibular migraine). Most of these agents, particularly those that are sedating, also have a potential to modulate the rate of compensation for vestibular damage. This consideration has become more relevant in recent years, as vestibular rehabilitation physical therapy is now often recommended in an attempt to promote compensation. Accordingly, therapy of vertigo is optimised when the prescriber has detailed knowledge of the pharmacology of medications being administered as well as the precise actions being sought. There are four broad causes of vertigo, for which specific regimens of drug therapy can be tailored. Otological vertigo includes disorders of the inner ear such as Ménière's disease, vestibular neuritis, benign paroxysmal positional vertigo (BPPV) and bilateral vestibular paresis. In both Ménière's disease and vestibular neuritis, vestibular suppressants such as anticholinergics and benzodiazepines are used. In Ménière's disease, salt restriction and diuretics are used in an attempt to prevent flare-ups. In vestibular neuritis, only brief use of vestibular suppressants is now recommended. Drug treatments are not presently recommended for BPPV and bilateral vestibular paresis, but physical therapy treatment can be very useful in both. Central vertigo includes entities such as vertigo associated with migraine and certain strokes. Prophylactic agents (L-channel calcium channel antagonists, tricyclic antidepressants, beta-blockers) are the mainstay of treatment

  3. Pharmacologic treatment of osteoarthritis.

    PubMed

    Pinals, R S

    1992-01-01

    Current pharmacotherapy for osteoarthritis (OA) is aimed at relief of pain and functional disability. Although an inflammatory component may be found in some cases, there is little evidence that anti-inflammatory drugs commonly used in the treatment of OA provide more relief than simple analgesics. A growing body of knowledge about the pathophysiology of OA now offers opportunities to develop interventions aimed at retarding the progressive degeneration of articular cartilage. This is a function of an imbalance between cartilage matrix synthesis and breakdown. New and experimental treatments include oral, parenteral, and intra-articular agents, some of which are chemicals and others biological products. Their modes of action have generally not been established in humans, but may be inferred from in vitro culture systems and animal models. These mechanisms include inhibition of synovial cell-derived cytokines and chondrocyte-derived degradative enzymes, inactivation of superoxide free radicals, stimulation of matrix synthesis, and enhancement of synovial fluid lubrication. Many of these treatments have been shown to provide short- or long-term symptomatic improvement in clinical trials. Protection of cartilage or promotion of repair has been demonstrated in animal studies, but not convincingly in human OA studies. PMID:1386287

  4. Pharmacologic treatment of pediatric insomnia.

    PubMed

    Owens, Judith A; Moturi, Sricharan

    2009-10-01

    Pediatric insomnia is common in children and adolescents, particularly in children who have comorbid medical, psychiatric, and neurodevelopmental disorders, and may be associated with cognitive, emotional, and psychosocial impairments that often result in significant caregiver burden. Although several behavioral interventions for pediatric insomnia are effective, there is a relative paucity of empiric evidence supporting the use of pharmacologic treatment. Sedative/hypnotic drugs are frequently used in clinical practice to treat pediatric insomnia, and guidelines for the use of these medications in general as well as for specific medications have been developed. This review presents expert consensus guidelines for the use of these medications in clinical practice, with a focus on the different classes of pharmacologic agents that are most commonly prescribed. PMID:19836701

  5. Pharmacological treatment of epilepsy today.

    PubMed

    Benna, P; Bergamasco, B

    1986-01-01

    The pharmacological treatment of epilepsy has not gone through remarkable changes in recent years. Treatment is based on few first choice drugs, the mechanism of action of which we do not yet know exactly. These include: phenobarbital, primidone, phenytoin, carbamazepine, valproic acid, ethosuximide, clonazepam. Choice of drug is determined by the kind of seizures presented by the patient, while successful treatment is determined by the kind of epilepsy. The present trend is the use of first line drugs in monotherapy, fixing individually the dosage according to the plasma levels. The results obtained with the GABA-agonists (progabide, gamma-vinyl GABA) and with some of the calcium-antagonists (flunarizine) seem promising. PMID:2886407

  6. Pharmacological Treatment of Uterine Fibroids

    PubMed Central

    Moroni, RM; Vieira, CS; Ferriani, RA; Candido-dos-Reis, FJ; Brito, LGO

    2014-01-01

    Uterine fibroids (UF) are common, benign gynecologic tumors, affecting one in three to four women, with estimates of up to 80%, depending on the population studied. Their etiology is not well established, but it is under the influence of several risk factors, such as early menarche, nulliparity and family history. More than 50% of affected women are asymptomatic, but the lesions may be related to bothersome symptoms, such as abnormal uterine bleeding, pelvic pain and bloating or urinary symptoms. The treatment of UF is classically surgical; however, various medical options are available, providing symptom control while minimizing risks and complications. A large number of clinical trials have evaluated commonly used medical treatments and potentially effective new ones. Through a comprehensive literature search using PubMed, EMBASE, CENTRAL, Scopus and Google Scholar databases, through which we included 41 studies out of 7658 results, we thoroughly explored the different pharmacological options available for management of UF, their indications, advantages and disadvantages. PMID:25364587

  7. Pharmacologic Treatment for Temporomandibular Disorders.

    PubMed

    Dym, Harry; Bowler, Dustin; Zeidan, Joseph

    2016-04-01

    Pharmacologic agents play an integral role in the overall management of temporomandibular joint disorder. The general dentist should be familiar with the different classes of drugs currently in use for dealing with this often complex medical/dental problem. PMID:27040290

  8. Treatment of Pancreatic Cancer with Pharmacological Ascorbate

    PubMed Central

    Cieslak, John A.; Cullen, Joseph J.

    2016-01-01

    The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that high-dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs. normal cells, suggesting a promising new role of ascorbate as a therapeutic agent. At physiologic concentrations, ascorbate functions as a reducing agent and antioxidant. However, when pharmacological ascorbate is given intravenously, it is possible to achieve millimolar plasma concentration. At these pharmacological levels, and in the presence of catalytic metal ions, ascorbate can induce oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in vitro and in vivo studies have demonstrated ascorbate oxidation occurs extracellularly, generating H2O2 flux into cells resulting in oxidative stress. Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts and displays synergistic cytotoxic effects when combined with gemcitabine in pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic cancer patients have demonstrated safety and potential efficacy. In this chapter, we will review the mechanism of ascorbate-induced cytotoxicity, examine the use of pharmacological ascorbate in treatment and assess the current data supporting its potential as an adjuvant in pancreatic cancer. PMID:26201606

  9. New approaches to pharmacological treatment of osteoporosis.

    PubMed Central

    Akesson, Kristina

    2003-01-01

    Osteoporosis has been recognized as a major public health problem for less than two decades. The increasing incidence of fragility fractures, such as vertebral, hip, and wrist fractures, first became apparent from epidemiological studies in the early and mid-1980s, when effective treatment was virtually unavailable. Pharmacological therapies that effectively reduce the number of fractures by improving bone mass are now available widely in countries around the world. Most current agents inhibit bone loss by reducing bone resorption, but emerging therapies may increase bone mass by directly promoting bone formation--as is the case with parathyroid hormone. Current treatment alternatives include bisphosphonates, calcitonin, and selective estrogen receptor modulators, but sufficient calcium and vitamin D are a prerequisite. The availability of evidence-based data that show reductions in the incidence of fractures of 30-50% during treatment has been a major step forward in the pharmacological prevention of fractures. With all agents, fracture reduction is most pronounced for vertebral fracture in high-risk individuals; alendronate and risedronate also may protect against hip fracture in the elderly. New approaches to pharmacological treatment will include further development of existing drugs, especially with regard to tolerance and frequency of dosing. New avenues for targeting the condition will emerge as our knowledge of the regulatory mechanisms of bone remodelling increases, although issues of tissue specificity may be difficult to solve. In the long term, information gained through knowledge of bone genetics may be used to adapt pharmacological treatments more precisely to each individual. PMID:14710507

  10. Pharmacological Treatment Effects on Eye Movement Control

    ERIC Educational Resources Information Center

    Reilly, James L.; Lencer, Rebekka; Bishop, Jeffrey R.; Keedy, Sarah; Sweeney, John A.

    2008-01-01

    The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to…

  11. Pharmacological Treatment of Cannabis Dependence

    PubMed Central

    Weinstein, A.M.; Gorelick, David A.

    2011-01-01

    Cannabis is the most frequently used illegal psychoactive substance in the world. There is a significant increase in the number of treatment admissions for cannabis use disorders in the past few years, and the majority of cannabis-dependent individuals who enter treatment have difficulty in achieving and maintaining abstinence. Thus, there is increased need for medications that can be used to treat this population. So far, no medication has been shown broadly and consistently effective; none has been approved by any national regulatory authority. Medications studied have included those that alleviate symptoms of cannabis withdrawal (e.g., dysphoric mood, irritability), those that directly affect endogenous cannabinoid receptor function, and those that have shown efficacy in treatment of other drugs of abuse or psychiatric conditions. Buspirone is the only medication to date that has shown efficacy for cannabis dependence in a controlled clinical trial. Results from controlled human laboratory studies and small open-label clinical trials suggest that dronabinol, the COMT inhibitor entacapone, and lithium may warrant further study. Recent pre-clinical studies suggest the potential of fatty acid amide hydrolase (FAAH) inhibitors such as URB597, endocannabinoid-metabolizing enzymes, and nicotinic alpha7 receptor antagonists such as methyllycaconitine (MLA). Controlled clinical trials are needed to evaluate the clinical efficacy of these medications and to validate the laboratory models being used to study candidate medications. PMID:21524266

  12. Pharmacological treatment of cannabis dependence.

    PubMed

    Weinstein, A M; Gorelick, David A

    2011-01-01

    Cannabis is the most frequently used illegal psychoactive substance in the world. There is a significant increase in the number of treatment admissions for cannabis use disorders in the past few years, and the majority of cannabis-dependent individuals who enter treatment have difficulty in achieving and maintaining abstinence. Thus, there is increased need for medications that can be used to treat this population. So far, no medication has been shown broadly and consistently effective; none has been approved by any national regulatory authority. Medications studied have included those that alleviate symptoms of cannabis withdrawal (e.g., dysphoric mood, irritability),those that directly affect endogenous cannabinoid receptor function, and those that have shown efficacy in treatment of other drugs of abuse or psychiatric conditions. Buspirone is the only medication to date that has shown efficacy for cannabis dependence in a controlled clinical trial. Results from controlled human laboratory studies and small open-label clinical trials suggest that dronabinol, the COMT inhibitor entacapone, and lithium may warrant further study. Recent pre-clinical studies suggest the potential of fatty acid amide hydrolase (FAAH) inhibitors such as URB597, endocannabinoid-metabolizing enzymes, and nicotinic alpha 7 receptor antagonists such as methyllycaconitine (MLA).Controlled clinical trials are needed to evaluate the clinical efficacy of these medications and to validate the laboratory models being used to study candidate medications. PMID:21524266

  13. Effectiveness of Psychological and Pharmacological Treatments for Nocturnal Enuresis.

    ERIC Educational Resources Information Center

    Houts, Arthur C.; And Others

    1994-01-01

    Assesses overall effectiveness of psychological and pharmacological treatments, relative effectiveness of specific treatments, and moderators of treatment effectiveness for nocturnal enuretic children via quantitative integration of research. Findings confirm that more children benefit from psychological than from pharmacological interventions and…

  14. Pharmacological treatment of exercise dyspnoea.

    PubMed

    Grazzini, M; Stendardi, L; Rosi, E; Scano, G

    2001-02-01

    A better understanding of the mechanisms of dyspnoea improves the clinician's ability to treat patients with shortness of breath. Any intervention that: 1) reduces ventilatory demands; 2) reduces ventilatory impedance; or 3) improves inspiratory muscle function, may relieve dyspnoea. Reduced ventilatory demand may be obtained by reducing metabolic load. Supplemental oxygen during exercise reduces exertional breathlessness and improves exercise tolerance, the decrease in dyspnoea being proportional to decrease in minute ventilation. Reduced ventilatory demand may also be obtained by decreasing the central drive. Opiates have been shown to decrease minute ventilation at rest and during submaximal exercise. They can alter the central processing of neural signals within the central nervous system to reduce sensations associated with breathing. Contrastingly, no consistent improvement in dyspnoea (versus placebo) has been shown with anxolytics. Decreasing central drive may also be obtained by altering pulmonary afferent information. Interventions that alter transmittal of afferent information to the central controller, potentially reduce dyspnoea. Reduction of ventilatory impedance is obtained by administering B2, anticholinergics or theophylline. B2 and anticholinergics act by modulating the increase in operational lung volumes and the inspiratory muscle effort during exercise. The mechanism by which theophylline relieves dyspnoea is probably related to a mechanism other than its bronchodilation alone. Alterations in respiratory muscle function are currently being detected in patients with chronic obstructive pulmonary disease, due to alteration in respiratory muscle energy balance. Nutritional repletion may improve respiratory muscle function but uncertainty remains as to whether nutritional repletion may relieve dyspnoea. The cumulative benefit of interventions targeting the pathophysiologic mechanism of dyspnoea must be identified for optimum treatment of patients

  15. Pharmacological Treatment of PTSD – Established and New Approaches

    PubMed Central

    Steckler, Thomas; Risbrough, Victoria

    2011-01-01

    A large proportion of humans will experience a traumatic event at least once in their lifetime, with up to 10% then going on to developing post-traumatic stress disorder (PTSD). In this review we will discuss established pharmacological interventions for PTSD as well as highlight novel therapeutic strategies undergoing extensive preclinical research as well as ongoing clinical research. Such strategies include prophylactic treatments and use of pharmacotherapy as adjunctive treatment with established trauma-focused psychological therapies. These potential treatment approaches include modulation of stress effects on memory consolidation after trauma (e.g. glucocorticoid, corticotropin releasing factor and norepinephrine signalling modulators), as well as putative cognitive enhancers that target mechanisms of conditioned fear extinction and reconsolidation (e.g. glucocorticoid receptor modulators and modulators of glutamate signalling such as positive allosteric modulators of glutamate receptors, glycine transporter inhibitors, glycine agonists, autoreceptor antagonists). We will discuss evidence for and against these potential novel treatment strategies and their limitations. PMID:21736888

  16. Pharmacological treatment of chronic obstructive pulmonary disease

    PubMed Central

    Montuschi, Paolo

    2006-01-01

    None of the drugs currently available for chronic obstructive pulmonary disease (COPD) are able to reduce the progressive decline in lung function which is the hallmark of this disease. Smoking cessation is the only intervention that has proved effective. The current pharmacological treatment of COPD is symptomatic and is mainly based on bronchodilators, such as selective β2-adrenergic agonists (short- and long-acting), anticholinergics, theophylline, or a combination of these drugs. Glucocorticoids are not generally recommended for patients with stable mild to moderate COPD due to their lack of efficacy, side effects, and high costs. However, glucocorticoids are recommended for severe COPD and frequent exacerbations of COPD. New pharmacological strategies for COPD need to be developed because the current treatment is inadequate. PMID:18044097

  17. New pharmacological treatment strategies for relapse prevention.

    PubMed

    Spanagel, Rainer; Vengeliene, Valentina

    2013-01-01

    Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a historical overview about relapse prevention strategies. We will then review the development of disulfiram, naltrexone, acamprosate, and nalmefene and discuss their neurobiological modes of action. Then the concept of convergent genomic analysis will be introduced for the discovery of new molecular treatment targets. Finally, we will provide convincing evidence for the use of N-methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs. Important conclusions of this review are: (i) learning from other addictive substances is very helpful-e.g., substitution therapies as applied to opiate addiction for decades could also be translated to alcoholics, (ii) the glutamate theory of alcohol addiction provides a convincing framework for the use of NMDA receptor antagonists as substitution drugs for alcohol-dependent patients, (iii) a combination of behavioral and pharmacological therapies may be the optimal approach for future treatment strategies-one promising example concerns the pharmacological disruption of reconsolidation processes of alcohol cue memories, (iv) given that many neurotransmitter systems are affected by chronic alcohol consumption, numerous druggable targets have been identified; consequently, a "cocktail" of different compounds will further improve the treatment situation, (v) in silico psychopharmacology, such as drug repurposing will yield new medications, and finally, (vi) the whole organism has to be taken into consideration to provide the best therapy for our patients. In summary, there is no other field in psychiatric research that has, in recent years, yielded so many novel, druggable targets and innovative treatment strategies than for alcohol addiction. However, it will still be several years before the majority of the "treatment-seeking population" will benefit

  18. Emerging pharmacologic targets and treatments for myocarditis.

    PubMed

    Jensen, Lionel D; Marchant, David J

    2016-05-01

    Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle. The primary clinical manifestations of myocarditis are heart failure and sudden death in children and young adults. Numerous interventions have been investigated for the treatment of myocarditis, including broad spectrum alteration of the immune response and antiviral treatments; however, success has been limited. Since the myocarditis treatment trials in the 1990s there has been an improved understanding of disease progression and new facets of the immune response have been discovered. This new information provides fresh opportunities to develop therapeutics to treat myocarditis. This review analyzes previous pharmacologic approaches including immunosuppression, high dose intravenous immunoglobulin treatment, immunoadsorption and antiviral treatments, and looks forward toward recently identified immune factors that can be exploited as targets for new treatments. Such strategies include bolstering beneficial regulatory T cells or mitigating the detrimental Th17 T cells which can drive autoimmunity in the heart. The surging interest of the application of humanized monoclonal antibodies makes targeting deleterious arms of the immune response like Th17 cells a tangible goal in the near future. Promising constituents of herbal remedies have also been identified that may hold potential as new pharmacological treatments for myocarditis, however, significant work remains to elucidate the pharmacokinetics and side-effects of these compounds. Finally, advances in our understanding of the function of Matrix Metalloproteinases yield another target for altering disease progression given their role in the development of fibrosis during Dilated Cardiomyopathy. In bringing to light the various new targets and treatments available since the last myocarditis treatment trials, the aim of this review is to explore the new treatments that are possible in new myocarditis treatment trials

  19. Pharmacologic Strategies for Treatment of Poisonings.

    PubMed

    Roberts, Eric; Gooch, Michael D

    2016-03-01

    Poisoning is the leading cause of injury-related mortality in the United States. Data suggest that nonmedical use of pharmaceuticals is increasing, along with a proportional increase in subsequent adverse events. The widespread use of illegal drugs contributes to the challenge, because these drugs may produce a wide array of clinical presentations that warrant time-critical recognition and treatment. Common legal and illegal poisonings highlighting clinical presentations in terms of toxidromes as a means of categorically recognizing these emergencies is the focus of this article. To optimize outcomes for situations such as these, pharmacologic considerations are discussed and explored. PMID:26897424

  20. Review of pharmacologic treatment of tinnitus.

    PubMed

    Murai, K; Tyler, R S; Harker, L A; Stouffer, J L

    1992-09-01

    Recent research on the pharmacologic treatment of tinnitus is reviewed, emphasizing studies in which controls have been used. Several double-blind cross-over studies have found that lidocaine can reduce tinnitus in about 50 to 75 percent of subjects. Unfortunately, it cannot be used clinically because it must be administered intravenously and its effects are very brief. Other drugs have been much less successful. A few controlled studies have found success rates between 33 and 56 percent using oxazepam, clonazepam, sodium amylobarbitone, flunarizine, and eperisone hydrochloride. None of these studies have been replicated, however. Closely controlled studies using specified etiologic subgroups with subjective and objective psychophysical measurements are needed. PMID:1359790

  1. Pharmacological treatment of obsessive-compulsive disorder

    PubMed Central

    Bloch, Michael H.

    2014-01-01

    Synopsis Obsessive-compulsive disorder (OCD) affects up to 2.5% of the population of the course of a lifetime and produces substantial morbidity. Approximately 70% of patients can experience significant symptomatic relief with appropriate pharmacotherapy. The selective serotonin reuptake inhibitors (SSRIs) are the main stay of pharmacological treatment. These are typically used at higher doses and for longer periods than in depression. Remission is, unfortunately, uncommon. Proven second-line treatments include the tricyclic clomipramine and the addition of low-dose neuroleptic medications. Other augmentation strategies have been explored for patients refractory to proven interventions, but they are not as of yet robustly supported by controlled studies. The combination of medication with psychotherapy is often used, though careful studies have not documented synergistic benefit in adult patients. OCD refractory to available treatments remains a profound clinical challenge. PMID:25150568

  2. Pharmacologic treatment of depression in late life

    PubMed Central

    Flint, A J

    1997-01-01

    A number of age-related factors, including changes in pharmacokinetics and pharmacodynamics, medical comorbidity and an increased risk of drug-drug interaction, can complicate the pharmacologic management of depression in late life. Nevertheless, over 80% of elderly depressed patients will eventually respond to vigorous treatment and, when treated over 2 years, up to 75% of those will not have a relapse or recurrence of depression. This article reviews a number of issues relating to the pharmacotherapy of depression in elderly people. In particular, it discusses the similarities and differences between various antidepressant medications, issues pertaining to dosing and length of treatment, and management of the patient who does not respond to first-line treatment. The author emphasizes that, because of the high risk of relapse and recurrence, a long-term collaboration between the patient and the physician is required to successfully manage depression in late life. PMID:9347777

  3. [Pharmacological treatment of the premature ejaculation].

    PubMed

    Jurado López, A R

    2014-07-01

    Biomedical approach to premature ejaculation (PE) has permited a better phisiopatologycal knowledge and so the use of pharmacological agents for the treatment of this sexual dysfuncion. Most of the studies to evaluate the eficacy of these drugs were not carried at all the parameters which actually define PE: intravaginal ejaculatory latencie time (IELT) tested with watch, ejaculation control self perception cuantification (questionaries) and cuantification of generated consequences in patient and partner, if it existes. For this reason, it is difficult to analyse the scientific evidence and we use medicines with no approved indication for PE ("off label"). This text is a review of pharmacologycal agents with no approved indication (PDE type 5 inhibitors, α-blockers, tramadol, SSRI, clomipramine), and pharmacologycal agents developed to be used in the treatment of PE and having got indication in this sexual dysfunction or "on label" drugs (topic anesthesics, dapoxetine). PMID:25953037

  4. Pharmacologic treatment of hypertensive disorders during pregnancy.

    PubMed

    Yankowitz, Jerome

    2004-01-01

    Pregnancy complicated by hypertension is a common problem faced by clinicians. It can lead to substantial maternal and/or fetal/neonatal morbidity and mortality. There are a variety of medications that can be used during pregnancy either for treatment of significant chronic hypertension or in cases of acute severe hypertension. Most antihypertensive drugs have been shown to be safe for use in pregnancy. A variety of medications are available to treat more severe hypertension, although the use of pharmacologic therapy to treat mild chronic hypertension during pregnancy has not been supported in the literature. The data are more limited concerning drugs that would be used in the event of hypertensive emergencies or in an intensive care setting; however, in such a situation, maternal health and life become paramount and, despite lack of good studies, appropriate treatment should be rendered. PMID:15478474

  5. [Non pharmacologic treatment of neuropathic pain].

    PubMed

    Guastella, Virginie; Mick, Gérard; Laurent, Bernard

    2008-02-01

    Nondrug treatments of neuropathic pain should always begin at the same time as pharmacologic treatment. There are three types of nondrug treatment for neuropathic pain: physical, surgical, and "psychocorporal" and psychotherapeutic treatment. Transcutaneous electrical nerve stimulation (TENS) is a simple physical treatment that strengthens local inhibitory controls and is indicated in focal neuropathic pain when upstream stimulation is possible for a superficial sensitive nerve trunk. Destructive surgery is represented today by "DREZotomy", destruction of nociceptive fibers and their dorsal root entry zones. It is indicated essentially in intractable pain due to plexus avulsion. Functional surgery is implanted electric stimulation--either spinal or central (encephalic)--of structures that exert inhibitory control on the pain pathways. Spinal stimulation is performed at the level of the posterior spinal cord and is indicated essentially in segmental mononeuropathies refractory to drug treatment. Central stimulation is performed at the motor cortex and is indicated for refractory central pain. "Psychocorporal" techniques (relaxation, sophrology, hypnosis) are useful to reduce anxiety and neurovegetative hypertonicity, both factors that aggravate neuropathic pain. PMID:18191370

  6. Pharmacology for the treatment of premature ejaculation.

    PubMed

    Giuliano, François; Clèment, Pierre

    2012-07-01

    Male sexual response comprises four phases: excitement, including erection; plateau; ejaculation, usually accompanied by orgasm; and resolution. Ejaculation is a complex sexual response involving a sequential process consisting of two phases: emission and expulsion. Ejaculation, which is basically a spinal reflex, requires a tight coordination between sympathetic, parasympathetic, and somatic efferent pathways originating from different segments and area in the spinal cord and innervating pelvi-perineal anatomical structures. A major relaying and synchronizing role is played by a group of lumbar neurons described as the spinal generator of ejaculation. Excitatory and inhibitory influences from sensory genital and cerebral stimuli are integrated and processed in the spinal cord. Premature ejaculation (PE) can be defined by ≤1-min ejaculatory latency, an inability to delay ejaculation, and negative personal consequences. Because there is no physiological impairment in PE, any pharmacological agent with central or peripheral mechanism of action that is delaying the ejaculation is a drug candidate for the treatment of PE. Ejaculation is centrally mediated by a variety of neurotransmitter systems, involving especially serotonin and serotonergic pathways but also dopaminergic and oxytocinergic systems. Pharmacological delay of ejaculation can be achieved either by inhibiting excitatory or reinforcing inhibitory pathways from the brain or the periphery to the spinal cord. PE can be treated with long-term use of selective serotonin-reuptake inhibitors (SSRIs) or tricyclic antidepressants. Dapoxetine, a short-acting SSRI, is the first treatment registered for the on-demand treatment of PE. Anesthetics applied on the glans penis have the ability to lengthen the time to ejaculation. Targeting oxytocinergic, neurokinin-1, dopaminergic, and opioid receptors represent future avenues to delaying ejaculation. PMID:22679220

  7. Pharmacological maintenance treatments of opiate addiction

    PubMed Central

    Bell, James

    2014-01-01

    For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been ‘programmatic’, with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some ‘nonresponders’ and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy. PMID:23210630

  8. Advances in pharmacological treatment of migraine.

    PubMed

    Diener, H C; Limmroth, V

    2001-10-01

    Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise. This review summarises new treatment options both for the therapy of the acute attack as well as for migraine prophylaxis. Analgesics like aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) are effective in treating migraine attacks. Few controlled trials were performed for the use of ergotamine or dihydroergotamine. These trials indicate inferior efficacy compared with serotonin (5-HT(1B/D)) agonists (triptans). The triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan), are highly effective. They improve headache as well as nausea, photo- and phonophobia. The different triptans show only minor differences in efficacy, headache recurrence and adverse effects. The knowledge of their different pharmacological profile allows a more specific treatment of the individual migraine characteristics. Migraine prophylaxis is recommended, when more than three attacks occur per month, if attacks do not respond to acute treatment or if side effects of acute treatment are severe. Substances with proven efficacy include the beta-blockers metoprolol and propranolol, the calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline. Recently anti-epileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for the prophylaxis of migraine. The use of botulinum toxin is under investigation. PMID:11772289

  9. [Pharmacological treatment of benign prostatic hyperplasia].

    PubMed

    Oelke, M; Martinelli, E

    2016-01-01

    The pharmacological treatment of benign prostatic hyperplasia (BPH) is indicated when men suffer from lower urinary tract symptoms (LUTS) but there are no absolute indications for prostate surgery or severe bladder outlet obstruction. Phytotherapy can be used in men with mild to moderate LUTS and alpha-blockers can quickly and effectively decrease the LUTS and symptomatic disease progression. Phosphodiesterase type 5 inhibitors (PDE5-I) are an alternative to alpha-blockers when men experience bothersome side effects from alpha-blockers or erectile dysfunction. If patients predominantly have bladder storage symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of alpha-blocker plus muscarinic receptor antagonist is more efficacious in reducing LUTS than the single drugs alone. The 5 alpha-reductase inhibitors (5ARI) can significantly decrease LUTS and disease progression (e.g. acute urinary retention and need for prostate surgery) in men with larger prostates (> 30-40 ml). The combination of 5ARI plus alpha-blocker can reduce LUTS and disease progression more effectively than drug monotherapy. Combination therapy with PDE5-I (tadalafil) plus 5ARI (finasteride) reduces LUTS more substantially than 5ARI alone and, additionally, PDE5-Is reduce the sexual side effects during 5ARI treatment. PMID:26676726

  10. Pharmacological and non-pharmacological treatments for nightmare disorder.

    PubMed

    Nadorff, Michael R; Lambdin, Karen K; Germain, Anne

    2014-04-01

    Interest in the treatment of nightmares has greatly increased over the last several years as research has demonstrated the clinical significance of nightmare disorder. This paper provides an overview of nightmare disorder, its clinical relevance, and the leading treatments that are available. In particular, the paper defines nightmare disorder and then summarize the recent literature examining the clinical relevance of nightmare disorder, including its relation to post-traumatic stress disorder and other psychiatric conditions. The relation between nightmares and suicidality is also discussed. Recent findings on the treatment of nightmare with imagery rehearsal therapy and prazosin are then summarized. Lastly, the paper comments on potential future uses of nightmare treatment including using imagery rehearsal therapy or prazosin as a first-line intervention for post-traumatic stress disorder and using these treatments as an adjunctive therapy to reduce suicide risk in those at risk of suicide with nightmares. PMID:24892897

  11. Cerebral Vasospasm Pharmacological Treatment: An Update

    PubMed Central

    Siasios, Ioannis; Kapsalaki, Eftychia Z.; Fountas, Kostas N.

    2013-01-01

    Aneurysmal subarachnoid hemorrhage- (aSAH-) associated vasospasm constitutes a clinicopathological entity, in which reversible vasculopathy, impaired autoregulatory function, and hypovolemia take place, and lead to the reduction of cerebral perfusion and finally ischemia. Cerebral vasospasm begins most often on the third day after the ictal event and reaches the maximum on the 5th–7th postictal days. Several therapeutic modalities have been employed for preventing or reversing cerebral vasospasm. Triple “H” therapy, balloon and chemical angioplasty with superselective intra-arterial injection of vasodilators, administration of substances like magnesium sulfate, statins, fasudil hydrochloride, erythropoietin, endothelin-1 antagonists, nitric oxide progenitors, and sildenafil, are some of the therapeutic protocols, which are currently employed for managing patients with aSAH. Intense pathophysiological mechanism research has led to the identification of various mediators of cerebral vasospasm, such as endothelium-derived, vascular smooth muscle-derived, proinflammatory mediators, cytokines and adhesion molecules, stress-induced gene activation, and platelet-derived growth factors. Oral, intravenous, or intra-arterial administration of antagonists of these mediators has been suggested for treating patients suffering a-SAH vasospam. In our current study, we attempt to summate all the available pharmacological treatment modalities for managing vasospasm. PMID:23431440

  12. Pharmacology.

    PubMed

    Bolay, Hayrunnisa; Durham, Paul

    2010-01-01

    Headache treatment has been based primarily on experiences with non-specific drugs such as analgesics, non-steroidal anti-inflammatory drugs, or drugs that were originally developed to treat other diseases, such as beta-blockers and anticonvulsant medications. A better understanding of the basic pathophysiological mechanisms of migraine and other types of headache has led to the development over the past two decades of more target-specific drugs. Since activation of the trigeminovascular system and neurogenic inflammation are thought to play important roles in migraine pathophysiology, experimental studies modeling those events successfully predicted targets for selective development of pharmacological agents to treat migraine. Basically, there are two fundamental strategies for the treatment of migraine, abortive or preventive, based to a large degree on the frequency of attacks. The triptans, which exhibit potency towards selective serotonin (5-hydroxytryptamine, 5-HT) receptors expressed on trigeminal nerves, remain the most effective drugs for the abortive treatment of migraine. However, numerous preventive medications are currently available that modulate the excitability of the nervous system, particularly the cerebral cortex. In this chapter, the pharmacology of commercially available medications as well as drugs in development that prevent or abort headache attacks will be discussed. PMID:20816410

  13. Pharmacologic approaches to the treatment of cocaine dependence.

    PubMed Central

    Taylor, W A; Gold, M S

    1990-01-01

    When pharmacologic agents are considered in the treatment of cocaine addiction, the objective of such treatment--sustained abstinence--must be considered. Medication and medical approaches have been disappointing in the treatment of cocaine overdose. The central neurobiologic mechanism(s) involved in cocaine toxicity are poorly understood. Without a cocaine antagonist, pharmacologic approaches have been less than promising in preventing relapse. Various psychoactive medications have been tried in early cocaine abstinence, with some success. PMID:1971975

  14. [Review of current pharmacologic treatment of pain].

    PubMed

    Brasseur, L

    1997-01-01

    Pain is the main reason prompting patients to consult their physicians. In acute conditions, pain has a very particular significance as a warning sign, enabling the physician to attempt a diagnosis. Nevertheless, its detrimental effect upon the individual (even in the case of acute pain) and its cost to society are now widely acknowledged. There can be no doubt about the physical component of pain, but the psychological and social aspects should not be ignored, particularly in the case of chronic pain. There is no single therapeutic approach to pain and, more often than not, successful treatment comprises a combination of several. Pharmacological treatments are undeniably the most common approach. In clinical practice, recent advances have been based upon an improved understanding of 'old' substances such as morphine and, at the same time, research continues in the hope of finding the 'ideal' analgesic-effective in most situations but without adverse effects: this appears to be a somewhat utopian arm at present, considering the number of different causes of pain. An improved understanding of the physiological mechanisms of pain has led, within the field of clinical practice, to several methods of differentiating pain. These depend on whether or not pain responds to morphine, or on the type of pain: pain due to an excess of nociception, pain resulting from deafferentation (caused by damage to nerve pathways) in the central or peripheral nervous system and psychogenic (idiopathic) pain. Likewise, there are several different ways of classifying analgesic treatments: according to the intensity of pain, as with use of the WHO ladder (which is based on the notion of steps) for the treatment of cancer pain; according to the presumed physiopathological mechanism and, in particular, the response to morphine, and according to the presumed central or peripheral mechanism of the drugs. In reality, peripherally acting drugs can also have a central mechanism of action, just as

  15. Non-pharmacological treatments for COPD.

    PubMed

    Mulhall, Patrick; Criner, Gerard

    2016-07-01

    Chronic obstructive pulmonary disease (COPD) affects roughly 10% of the global population and is growing in prevalence annually. COPD is characterized by progressive non-reversible narrowing of airways mainly due to cigarette smoking. Therapeutic interventions aimed at altering this progressive disease course can largely be grouped into pharmacological or non-pharmacological therapies. The focus of this paper is on the non-pharmacological aspects of COPD management, reviewing the current literature to provide an evidence-based management approach. Non-pharmacological therapies reviewed in this article include the implementation of comprehensive care models utilizing a coordinated multidisciplinary team, tele-monitoring and patient-centred approach to optimize COPD care and improve compliance. Preventing progression of COPD via smoking cessation remains of paramount importance, and newer therapeutic options including electronic cigarettes show promise in small studies as cessation aids. COPD has systemic manifestations that can be ameliorated with the enrollment in pulmonary rehabilitation programmes, which focus on exercise endurance to improve dyspnoea and quality of life. Advanced therapeutics for COPD includes lung volume reduction surgery for a pre-specified cohort and minimally invasive bronchoscopic valves that in recent reviews show promise. Lastly, patients on maximal COPD therapy with progressive disease can be referred for lung transplantation; however, this often requires a highly selected and motivated patient and care team. Survival rates for lung transplantation are improving; thus, this procedure remains a viable option as more expertise and experience are gained. PMID:27099216

  16. Non-Pharmacological Treatments of Allergic Rhinitis (Neglected Treatments)

    PubMed Central

    Zohalinezhad, Mohammad Ebrahim; Zarshenas, Mohammad M.

    2016-01-01

    Background: Allergic rhinitis is the most common diseases affecting people in industrialized society. However, this is not a new disease and it was clinically described and treated for the first time by Rhazes (865-925 CE). The disease was also mentioned in “The Canon of Medicine” by Avicenna (980–1037). Methods: We searched in Scopus, Web of Science, and PubMed for “allergic rhinitis”, “interactions”, “non-prescription”, “prescription”, and in electronic copies of ITM sources the “canon” and “Al-Havi”. Results: Both Persian pioneers of Medicine recommended non-pharmacologic management as an important phase of the therapy. Their recommendations consisted of avoiding overeating and polydipsia, massage of the lower extremities, adjusting the duration and time of sleep, sleeping in the supine position, avoiding exposure of the head to cold air and taking a shower early in the morning. Conclusion: Although some aspects of their recommendations, such as massage of the lower extremities, avoiding of overeating and adjusting of sleep pattern were approved, but further cross-sectional and prospective studies are needed to confirm other non-pharmacological treatments.

  17. Pharmacology of anticoagulants used in the treatment of venous thromboembolism.

    PubMed

    Nutescu, Edith A; Burnett, Allison; Fanikos, John; Spinler, Sarah; Wittkowsky, Ann

    2016-01-01

    Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE. PMID:26780737

  18. Pharmacologic Approaches to the Treatment of Obstructive Sleep Apnea.

    PubMed

    White, David P

    2016-06-01

    The concept of pharmacologic therapy for obstructive sleep apnea (OSA) treatment has always been considered but no agent has had a large enough effect size to drive substantial adoption. A new construct of the pathophysiology of OSA is that there are 4 primary physiologic traits that dictate who develops OSA. These traits vary substantially between patients, meaning OSA may develop for quite different reasons. This encourages new thinking regarding pharmacologic therapy and continued attempts to find the ideal or acceptable drug. PMID:27236057

  19. Neuroscience of behavioral and pharmacological treatments for addictions

    PubMed Central

    Potenza, Marc N.; Sofuoglu, Mehmet; Carroll, Kathleen M.; Rounsaville, Bruce J.

    2011-01-01

    Summary Although substantial advances have been made in behavioral and pharmacological treatments for addictions, moving treatment development to the next stage may require novel ways of approaching addictions, particularly those derived from new findings regarding of the neurobiological underpinnings of addictions, while assimilating and incorporating relevant information from earlier approaches. In this review, we first briefly review theoretical and biological models of addiction and then describe existing behavioral and pharmacologic therapies for the addictions within this framework. We then propose new directions for treatment development and targets that are informed by recent evidence regarding the heterogeneity of addictions and the neurobiological contributions to these disorders. PMID:21338880

  20. [Pharmacological treatment of COPD. Where are we now?].

    PubMed

    Calle Rubio, Myriam; Pinedo Sierra, Celia; Rodríguez Hermosa, Juan Luis

    2010-12-01

    Current clinical guidelines recommend a step-wise approach to the pharmacological treatment of chronic obstructive pulmonary disease (COPD), with drugs being added according to the severity of airflow obstruction, symptoms, and the number of acute exacerbations in patients with severe disease. However, greater knowledge of the physiopathogenesis of this disease has led to COPD being considered a heterogeneous process in which therapeutic decisions should not be based exclusively on the results of spirometry. Treatment is increasingly individualized according to the patient's characteristics. The present article reviews the scientific evidence on the aims of treatment in COPD and the benefits achieved by the various pharmacological options available. PMID:21316549

  1. A Review of Pharmacologic Treatment for Compulsive Buying Disorder.

    PubMed

    Soares, Célia; Fernandes, Natália; Morgado, Pedro

    2016-04-01

    At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by searching the PubMed/MEDLINE database. Selection criteria were applied, and 21 studies were identified. Pharmacological classes reported included antidepressants, mood stabilizers, opioid antagonists, second-generation antipsychotics, and N-methyl-D-aspartate receptor antagonists. We found only placebo-controlled trials for fluvoxamine; none showed effectiveness against placebo. Three open-label trials reported clinical improvement with citalopram; one was followed by a double-blind discontinuation. Escitalopram was effective in an open-label trial but did not show efficacy in the double-blind phase. Memantine was identified as effective in a pilot open-label study. Fluoxetine, bupropion, nortriptyline, clomipramine, topiramate and naltrexone were only reported to be effective in clinical cases. According to the available literature, there is no evidence to propose a specific pharmacologic agent for compulsive buying disorder. Future research is required for a better understanding of both pathogenesis and treatment of this disorder. PMID:27067344

  2. [Pharmacology].

    PubMed

    González, José; Orero, Ana; Olmo, Vicente; Martínez, David; Prieto, José; Bahlsen, Jose Antonio; Zaragozá, Francisco; Honorato, Jesús

    2011-06-01

    Two of the main characteristics of western societies in the last fifty years have been the medicalization of the human life and the environmental degradation. The first one has forced human being to consider medicines use related to what would be rational, reasonable and well-reasoned. The second one brought us to a new ecologist conscience. In relation to the "human social system", the effects of medication can be considered very positive as a whole, particularly those related to the amazing increase of expectative and quality of life. But, along with those unquestionable beneficial effects, medicines have also caused some negative effects for other biotic and abiotic systems, such as microbian alterations and their undesirable consequences which have involved the massive use of antibiotics in medicine and veterinary, the uncontrolled elimination of millions of doses of all kind of drugs, additives and excipients, etc., as well as atmospheric contamination and degradation of forests and deep oceans which can have been caused by investigation and production of determinated drugs. In this context Pharmacology appears as a scientific discipline that studies the research (R), development (D), production (P), and utilization (U) of drugs and medical substances in relation to the environment. From a farmaecologic perspective the drugs utilization has its development in three main contexts, all of them closely related: prescription quality, farmaceutical care, and patient's active participation in his own disease and treatment. PMID:21666997

  3. [Pharmacological treatment of syndromes of aggressivity].

    PubMed

    Itil, T M

    1978-01-01

    In the treatment of violent-aggressive behavior, four major groups of drugs emerged: 1. Major tranquilizers in the treatment of aggressive-violent behavior associated with psychotic syndromes. 2. Anti-epileptic drugs such as diphenylhydantoin and barbiturates in the treatment of aggressive-violent behavior within the epileptic syndrome. 3. Psychostimulants in the treatment of aggressive behavior of adolescents and children within behavior disturbances. 4. Anti-male hormones such as cyproterone acetate in the treatment of violent-aggressive behavior associated with pathological sexual hyperactivity. Whereas each category of drug is predominantly effective in one type of aggressive syndrome, it may also be effective in other conditions as well. Aggression as a result of a personality disorder is most difficult to treat with drugs. PMID:34189

  4. Pharmacological and Non-pharmacological Treatment Options for Depression and Depressive Symptoms in Hemodialysis Patients

    PubMed Central

    Grigoriou, Stefania S.; Karatzaferi, Christina; Sakkas, Giorgos K.

    2015-01-01

    Depression is a mental disorder with a high prevalence among patients with end stage renal disease (ESRD). It is reported that depression afflicts approximately 20-30% of this patient population, being associated, amongst other, with high mortality rate, low adherence to medication and low perceived quality of life. There is a variety of medications known to be effective for the treatment of depression but due to poor adherence to treatment as well as due to the high need for medications addressing other ESRD comorbidities, depression often remains untreated. According to the literature, depression is under-diagnosed and undertreated in the majority of the patients with chronic kidney disease. In the current review the main pharmacological and non-pharmacological approaches and research outcomes for the management of depressive symptoms in hemodialysis patients are discussed. PMID:26973957

  5. Pharmacologic treatments for pulmonary hypertension: exploring pharmacogenomics

    PubMed Central

    Duarte, Julio D; Hanson, Rebekah L; Machado, Roberto F

    2013-01-01

    Pulmonary hypertension (PH) is a disease with multiple etiologies and is categorized into five broad groups. Of these groups, pulmonary arterial hypertension (PAH) is the most studied and, therefore, all of the currently available drug classes (prostacyclin analogs, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors) were developed to treat PAH. Thus, limited treatment data exist for the less-studied non-PAH forms of PH. Pharmacogenomics can be a tool to better understand the pathways involved in PH, as well as to improve personalization of therapy. However, little pharmacogenomic research has been carried out on this disease. New treatments for PH are on the horizon, deriving from both repurposed currently available drugs and novel therapeutics. PMID:23668740

  6. Non-pharmacological treatment of Helicobacter pylori.

    PubMed

    Shmuely, Haim; Domniz, Noam; Yahav, Jacob

    2016-05-01

    Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies. PMID:27158532

  7. Non-pharmacological treatment of Helicobacter pylori

    PubMed Central

    Shmuely, Haim; Domniz, Noam; Yahav, Jacob

    2016-01-01

    Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies. PMID:27158532

  8. Pharmacological treatment of cardiac glycoside poisoning.

    PubMed

    Roberts, Darren M; Gallapatthy, Gamini; Dunuwille, Asunga; Chan, Betty S

    2016-03-01

    Cardiac glycosides are an important cause of poisoning, reflecting their widespread clinical usage and presence in natural sources. Poisoning can manifest as varying degrees of toxicity. Predominant clinical features include gastrointestinal signs, bradycardia and heart block. Death occurs from ventricular fibrillation or tachycardia. A wide range of treatments have been used, the more common including activated charcoal, atropine, β-adrenoceptor agonists, temporary pacing, anti-digoxin Fab and magnesium, and more novel agents include fructose-1,6-diphosphate (clinical trial in progress) and anticalin. However, even in the case of those treatments that have been in use for decades, there is debate regarding their efficacy, the indications and dosage that optimizes outcomes. This contributes to variability in use across the world. Another factor influencing usage is access. Barriers to access include the requirement for transfer to a specialized centre (for example, to receive temporary pacing) or financial resources (for example, anti-digoxin Fab in resource poor countries). Recent data suggest that existing methods for calculating the dose of anti-digoxin Fab in digoxin poisoning overstate the dose required, and that its efficacy may be minimal in patients with chronic digoxin poisoning. Cheaper and effective medicines are required, in particular for the treatment of yellow oleander poisoning which is problematic in resource poor countries. PMID:26505271

  9. Acid peptic diseases: pharmacological approach to treatment

    PubMed Central

    Mejia, Alex; Kraft, Walter K

    2011-01-01

    Acid peptic disorders are the result of distinctive, but overlapping pathogenic mechanisms leading to either excessive acid secretion or diminished mucosal defense. They are common entities present in daily clinical practice that, owing to their chronicity, represent a significant cost to healthcare. Key elements in the success of controlling these entities have been the development of potent and safe drugs based on physiological targets. The histamine-2 receptor antagonists revolutionized the treatment of acid peptic disorders owing to their safety and efficacy profile. The proton-pump inhibitors (PPIs) represent a further therapeutic advance due to more potent inhibition of acid secretion. Ample data from clinical trials and observational experience have confirmed the utility of these agents in the treatment of acid peptic diseases, with differential efficacy and safety characteristics between and within drug classes. Paradigms in their speed and duration of action have underscored the need for new chemical entities that, from a single dose, would provide reliable duration of acid control, particularly at night. Moreover, PPIs reduce, but do not eliminate, the risk of ulcers in patients taking NSAIDs, reflecting untargeted physiopathologic pathways and a breach in the ability to sustain an intragastric pH of more than 4. This review provides an assessment of the current understanding of the physiology of acid production, a discussion of medications targeting gastric acid production and a review of efficacy in specific acid peptic diseases, as well as current challenges and future directions in the treatment of acid-mediated diseases. PMID:21822447

  10. Evidence-Based Pharmacologic Treatment of Pediatric Bipolar Disorder.

    PubMed

    Findling, Robert L

    2016-01-01

    Pharmacotherapy is an important component of treatment for children and adolescents with bipolar disorder. The body of evidence supporting safe and effective treatments in this population is growing. Available data provide information on the risks and benefits of pharmacologic agents used for acute manic, mixed, and depressive episodes as well as for maintenance treatment. Lithium, anticonvulsants, and antipsychotics comprise the armamentarium for treating pediatric bipolar disorder. When selecting treatment, clinicians must consider the efficacy and side effect profile of potential pharmacotherapies, as well as the patient's history, including the presence of comorbidities, in order to develop a treatment plan that will ensure optimal outcomes. PMID:27570928

  11. Pharmacologic Options for the Treatment of Sarcopenia.

    PubMed

    Morley, John E

    2016-04-01

    Sarcopenia is now clinically defined as a loss of muscle mass coupled with functional deterioration (either walking speed or distance or grip strength). Based on the FRAX studies suggesting that the questions without bone mineral density can be used to screen for osteoporosis, there is now a valid simple questionnaire to screen for sarcopenia, i.e., the SARC-F. Numerous factors have been implicated in the pathophysiology of sarcopenia. These include genetic factors, mitochondrial defects, decreased anabolic hormones (e.g., testosterone, vitamin D, growth hormone and insulin growth hormone-1), inflammatory cytokine excess, insulin resistance, decreased protein intake and activity, poor blood flow to muscle and deficiency of growth derived factor-11. Over the last decade, there has been a remarkable increase in our understanding of the molecular biology of muscle, resulting in a marked increase in potential future targets for the treatment of sarcopenia. At present, resistance exercise, protein supplementation, and vitamin D have been established as the basic treatment of sarcopenia. High-dose testosterone increases muscle power and function, but has a number of potentially limiting side effects. Other drugs in clinical development include selective androgen receptor molecules, ghrelin agonists, myostatin antibodies, activin IIR antagonists, angiotensin converting enzyme inhibitors, beta antagonists, and fast skeletal muscle troponin activators. As sarcopenia is a major predictor of frailty, hip fracture, disability, and mortality in older persons, the development of drugs to treat it is eagerly awaited. PMID:26100650

  12. [Treatment of generalized anxiety: new pharmacologic approaches].

    PubMed

    Boulenger, J P

    1995-01-01

    First defined as a residual diagnostic category in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), Generalized Anxiety Disorder (GAD) was until recently one of the least studied and least clearly conceptualized of the anxiety disorders. The clinical definition of GAD has however improved up to the fourth edition of the DSM where the disorder is now characterized as a chronic state of apprehensive expectation and uncontrollable worry concerning multiple daily life events or activities and accompanied with at least 3 symptoms belonging to a list of six common manifestations of psychic or motor tension. Clinical research demonstrating the stability and the specificity of somatic symptoms clearly support the validity of the diagnosis of GAD despite possible difficulties in the differential diagnosis with other chronic conditions or axis II disorders such as dysthymia or mixed anxiety-depressive disorder. After benzodiazepines (BZD) and 5-HT1A agonists like buspirone, several other types of new anxiolytic drugs have been developed for the treatment of GAD. Partial agonists at GABA-BZD receptor sites may offer the advantage of a better efficacy vs side-effects ratio over classical BZDs; however, systematic comparative clinical trials will have to demonstrate the clinical relevance of the encouraging results obtained with these drugs, at the experimental level, during studies in healthy volunteers and during the first placebo-controlled trials. Furthermore, the recent description of GABA-receptor's subunits clearly suggest that the development of drugs acting at this level and devoided of psychomotor or withdrawal side-effects is a target that is worth pursuing. On the other hand, the development of 5-HT2 and 5-HT3 antagonists is also of interest for the treatment of GAD since it could provide new anxiolytic drugs without these side-effects and thus easier to administer on a long-term basis corresponding to the chronicity of GAD

  13. Migraine: pathophysiology, pharmacology, treatment and future trends.

    PubMed

    Villalón, Carlos M; Centurión, David; Valdivia, Luis Felipe; de Vries, Peter; Saxena, Pramod R

    2003-03-01

    Migraine treatment has evolved into the scientific arena, but it seems still controversial whether migraine is primarily a vascular or a neurological dysfunction. Irrespective of this controversy, the levels of serotonin (5-hydroxytryptamine; 5-HT), a vasoconstrictor and a central neurotransmitter, seem to decrease during migraine (with associated carotid vasodilatation) whereas an i.v. infusion of 5-HT can abort migraine. In fact, 5-HT as well as ergotamine, dihydroergotamine and other antimigraine agents invariably produce vasoconstriction in the external carotid circulation. The last decade has witnessed the advent of sumatriptan and second generation triptans (e.g. zolmitriptan, rizatriptan, naratriptan), which belong to a new class of drugs, the 5-HT1B/1D/1F receptor agonists. Compared to sumatriptan, the second-generation triptans have a higher oral bioavailability and longer plasma half-life. In line with the vascular and neurogenic theories of migraine, all triptans produce selective carotid vasoconstriction (via 5-HT1B receptors) and presynaptic inhibition of the trigeminovascular inflammatory responses implicated in migraine (via 5-HT1D/5-ht1F receptors). Moreover, selective agonists at 5-HT1D (PNU-142633) and 5-ht1F (LY344864) receptors inhibit the trigeminovascular system without producing vasoconstriction. Nevertheless, PNU-142633 proved to be ineffective in the acute treatment of migraine, whilst LY344864 did show some efficacy when used in doses which interact with 5-HT1B receptors. Finally, although the triptans are effective antimigraine agents producing selective cranial vasoconstriction, efforts are being made to develop other effective antimigraine alternatives acting via the direct blockade of vasodilator mechanisms (e.g. antagonists at CGRP receptors, antagonists at 5-HT7 receptors, inhibitors of nitric oxide biosynthesis, etc). These alternatives will hopefully lead to fewer side effects. PMID:15320857

  14. [Non pharmacological treatment for bipolar disorder].

    PubMed

    Mirabel-Sarron, Christine; Giachetti, Raphaël

    2012-12-01

    Bipolar disorder is a chronic and recurring disorder associated with significant psychosocial impairment. A number of psychosocial interventions have been developed to address impairment. The consensus makes mood stabilizer the treatment of bipolar disorder. However, numerous patients are not in complete remission despite a controlled observance. Every patient can follow a psycho educational program. What this paper adds. The review identifies that a range of interventions have demonstrated efficacy in extended periods of euthymia, improved social and occupational functioning and alleviation of subsyndromal symptoms. Adjunctive, short-term psychotherapies have been shown to offer fairly consistent benefits to bipolar disorder patients. Cognitive-behavioural therapy, family-focused therapy, and psychoeducation offer the most robust efficacy in regard to relapse prevention. The most complex situations including comorbidities can be helped by behavioral and cognitive therapy for bipolar disorder. Evaluations emphasize positive impact. The psychosocial interventions reviewed provide mental health nurses with evidence-based approaches to improving mental health care for patients with bipolar disorder. There is a need for mental health nurses to conduct high quality trials of the clinical effectiveness of these interventions. PMID:23395231

  15. Music therapy as a non-pharmacological treatment for epilepsy.

    PubMed

    Liao, Huan; Jiang, Guohui; Wang, Xuefeng

    2015-01-01

    Epilepsy is one of the most common neurological diseases. Currently, the primary methods of treatment include pharmacological and surgical treatment. However, approximately one-third of patients exhibit refractory epilepsy. Therefore, a novel approach to epilepsy treatment is necessary. Several studies have confirmed that music therapy can be effective at reducing seizures and epileptiform discharges, thus providing a new option for clinicians in the treatment of epilepsy. Although the underlying mechanism of music therapy is unknown, it may be related to resonance, mirror neurons, dopamine pathways and parasympathetic activation. Large sample, multicenter, randomized double-blind and more effectively designed studies are needed for future music therapy studies. PMID:26196169

  16. Neuroimaging correlates of pharmacological and psychological treatments for specific phobia.

    PubMed

    Linares, Ila M; Chags, Marcos H N; Machado-de-Sousa, João P; Crippa, José A S; Hallak, Jaime E C

    2014-01-01

    Specific phobia is an anxiety disorder characterized by irrational fear and avoidance of specific things or situations, interfering significantly with the patients' daily life. Treatment for the disorder consists of both pharmacological and psychological approaches, mainly cognitive behavioral therapy (CBT). Neuroimaging techniques have been used in an attempt to improve our understanding of the neurobiology of SP and of the effects of treatment options available. This review describes the design and results of eight articles investigating the neuroimaging correlates of pharmacological and psychological treatments for SP. The studies show that CBT is effective in SP, leading to a reduction of anxiety symptoms that is accompanied by functional alterations in the brain. The results of pharmacological interventions for SP are less uniform, but suggest that the partial agonist of the NMDA (N-methyl D-aspartate) receptor DCS (D-cycloserine) can be used in combination with psychotherapy techniques for the achievement of quicker treatment response and that DCS modulates the function of structures implicated in the neurobiology of SP. Further research should explore the augmentation of CBT treatment with DCS in controlled trials. PMID:24923351

  17. Pharmacologic Treatment Strategies in Children with Type 2 Diabetes Mellitus

    PubMed Central

    Urakami, Tatsuhiko; Kuwabara, Remi; Habu, Masako; Yoshida, Ayako; Okuno, Misako; Suzuki, Junichi; Takahashi, Shori; Mugishima, Hideo

    2013-01-01

    We treated 80 obese and 28 nonobese children diagnosed as having type 2 diabetes mellitus (T2DM). Among these patients, 26 obese and 23 nonobese children were assigned to pharmacologic therapies during the course of diabetes. Pharmacologic therapies were started if the HbA1c (NGSP) value exceeded 7.0% despite dietary and exercise management. For the 26 obese patients, metformin alone or in combination with an additional medication was frequently used. Only 2 patients independently received sulfonylureas (SUs) in the form of glimepiride. In addition, 9 patients were treated with basal insulin supported with oral hypoglycemic drugs (OHDs) or biphasic premix insulin. On the other hand, the 23 nonobese patients were frequently treated with insulin alone or in combination with an additional medication followed by SUs. The nonobese patients tended to require pharmacologic therapies, in particular insulin, at an earlier stage of diabetes as compared with the obese patients. New antidiabetic drugs, DPP-4 inhibitors and GLP-1 receptor agonists, seemed to exert positive effects on glycemic control without occurrence of hypoglycemic episodes in some patients regardless of the type of diabetes. These results suggest that pharmacologic treatment strategies in childhood T2DM should be tailored to individual patient characteristics. PMID:23966754

  18. Treatment de-escalation in HPV-positive oropharyngeal carcinoma: ongoing trials, critical issues and perspectives.

    PubMed

    Mirghani, H; Amen, F; Blanchard, P; Moreau, F; Guigay, J; Hartl, D M; Lacau St Guily, J

    2015-04-01

    Due to the generally poor prognosis of head and neck squamous cell carcinoma (HNSCC), treatment has been intensified, these last decades, leading to an increase of serious side effects. High-risk human papillomavirus (HR-HPV) infection has been recently etiologically linked to a subset of oropharyngeal squamous cell carcinoma (OPSCC), which is on the increase. These tumors are different, at the clinical and molecular level, when compared to tumors caused by traditional risk factors. Additionally, their prognosis is much more favorable which has led the medical community to consider new treatment strategies. Indeed, it is possible that less intensive treatment regimens could achieve similar efficacy with less toxicity and improved quality of life. Several clinical trials, investigating different ways to de-escalate treatment, are currently ongoing. In this article, we review these main approaches, discuss the rationale behind them and the issues raised by treatment de-escalation in HPV-positive OPSCC. PMID:24622970

  19. Integrating electrodermal biofeedback into pharmacologic treatment of grand mal seizures

    PubMed Central

    Scrimali, Tullio; Tomasello, Damiana; Sciuto, Massimo

    2015-01-01

    Electrodermal activity (EDA) and electrodermal biofeedback, when integrated with pharmacologic treatments, indicate promising methods for the treatment of grand mal seizures. They can be used to monitor patient arousal and help patients learn new strategies to better cope with stress and anxiety. Our proposed method can possibly reduce the number of crises for patients who are dependent on pharmacologic therapy and can improve their quality of life. This article describes the scientific background of electrodermal monitoring and electrodermal biofeedback for patients affected by grand mal seizures. In this study, we have reported a clinical case study. The patient was treated for 2 years with electrodermal biofeedback to augment pharmacologic treatments. The trial has been designed in accordance with “n = 1 case study research”. Our results have shown that our methods could achieve a significant reduction in grand mal seizures and sympathetic arousal when applied. The patient under consideration was also relaxed and exhibited greater competency to cope with stress. Additionally, the patient’s sense of mastery and self-efficacy was enhanced. PMID:26029078

  20. Integrating electrodermal biofeedback into pharmacologic treatment of grand mal seizures.

    PubMed

    Scrimali, Tullio; Tomasello, Damiana; Sciuto, Massimo

    2015-01-01

    Electrodermal activity (EDA) and electrodermal biofeedback, when integrated with pharmacologic treatments, indicate promising methods for the treatment of grand mal seizures. They can be used to monitor patient arousal and help patients learn new strategies to better cope with stress and anxiety. Our proposed method can possibly reduce the number of crises for patients who are dependent on pharmacologic therapy and can improve their quality of life. This article describes the scientific background of electrodermal monitoring and electrodermal biofeedback for patients affected by grand mal seizures. In this study, we have reported a clinical case study. The patient was treated for 2 years with electrodermal biofeedback to augment pharmacologic treatments. The trial has been designed in accordance with "n = 1 case study research". Our results have shown that our methods could achieve a significant reduction in grand mal seizures and sympathetic arousal when applied. The patient under consideration was also relaxed and exhibited greater competency to cope with stress. Additionally, the patient's sense of mastery and self-efficacy was enhanced. PMID:26029078

  1. Pharmacologic treatment to improve venous leg ulcer healing.

    PubMed

    Raffetto, Joseph D; Eberhardt, Robert T; Dean, Steven M; Ligi, Daniela; Mannello, Ferdinando

    2016-07-01

    Pharmacologic treatment for venous leg ulcers (VLUs) is an adjuvant treatment to compression therapy. It encompasses a variety of plant-derived and synthetic compounds with properties that alter venous microcirculation, endothelial function, and leukocyte activity to promote VLU healing. These compounds are often referred to as venotonics or venoactive drugs but have also been referred to as edema-protective agents, phlebotonics, vasoprotectors, phlebotropics, and venotropics. The exact mechanism of their ability to heal VLUs is not known; however, clinical trials support their efficacy. This evidence-based review assesses randomized clinical trials and meta-analyses with the objective of determining the effectiveness of venotonics to promote VLU healing. PMID:27318060

  2. [Dual diagnosis in anxiety disorders: pharmacologic treatment recommendations].

    PubMed

    Sáiz Martínez, Pilar Alejandra; Jimenez Treviño, Luis; Díaz Mesa, Eva M; García-Portilla González, M Paz; Marina González, Pedro; Al-Halabí, Susana; Szerman, Néstor; Bobes García, Julio; Ruiz, Pedro

    2014-01-01

    Anxiety disorders and substance use disorders are highly comorbid (between 18% and 37%), and such comorbidity complicates treatment and worsens prognosis (including higher suicide risk). There are not many research works on the specific pharmacologic treatment of dual comorbid anxiety disorders. Most authors recommend a simultaneous approach of both, anxiety and substance use, disorders. Research data on pharmacotherapy suggest that psychotropics used in the treatment of anxiety disorders are also effective in dual diagnosis. SSRIs are considered first-line therapy in the treatment of dual anxiety while benzodiacepines should be avoided. New generation antiepileptic have shown efficacy in case series and open label studies in the latest years, thus being a promising treatment option for dual comorbid anxiety disorders, specially pregabalin in generalized anxiety disorder. PMID:25314041

  3. [The pharmacological treatment of obesity: past, present and future].

    PubMed

    Simonyi, Gábor; Pados, Gyula; Medvegy, Mihály; Bedros, J Róbert

    2012-03-11

    Currently, obesity presents one of the biggest health problems. Management strategies for weight reduction in obese individuals include changes in life style such as exercise and diet, behavioral therapy, and pharmacological treatment, and in certain cases surgical intervention. Diet and exercise are best for both prevention and treatment, but both require much discipline and are difficult to maintain. Drug treatment of obesity offer a possible adjunct, but it may only have modest results, limited by side effects; furthermore, the weight lowering effects last only as long as the drug is being taken and, unfortunately, as soon as the administration is stopped, the weight is regained. These strategies should be used in a combination for higher efficacy. Drugs used to induce weight loss have various effects: they increase satiety, reduce the absorption of nutrients or make metabolism faster; but their effect is usually moderate. In the past, several drugs were used in the pharmacological therapy of weight reduction including thyroid hormone, dinitrophenol, amphetamines and their analogues, e.g. fenfluramine, At present, only orlistat is available in the long term treatment (≥ 24 weeks) of obesity as sibutramine and rimonabant were withdrawn form the market. Several new anti-obesity drugs are being tested at present, and liraglutide, a GLP-1 analogue (incretin mimetic), is the most promising one. PMID:22370224

  4. Pharmacologic treatment of hand-, knee- and hip-osteoarthritis.

    PubMed

    Bobacz, Klaus

    2013-05-01

    Osteoarthritis (OA) is a joint disease of high prevalence and affects > 90 % of the population, depending on several risk factors. Symptomatic OA is less frequent, but requires an individually tailored therapeutic regimen consisting of non-pharmacological and pharmacological treatment modalities. Pharmacologic therapy, however, is mainly limited to analgetic and anti-inflammatory agents; structure modifying remedies do not exist. The therapeutic approach to hand-, knee- and hip-OA is basically similar and differs only at some minor points. Generally, topical agents or paracetamol are recommended as first-line agents. If unsuccessful oral non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2-selctive inhibitors should be introduced. Tramadol is an option in the case patients will not respond satisfactorily to NSAIDs. Glucosamine and chondroitine sulphate are no longer recommended in knee and hip OA, but chondroitine might be efficient in treating hand OA. Oral NSAIDs should be prescribed with caution due to potential side effects. Opioids are not recommended as their benefits are outweighed by an increased risk for serious adverse events. PMID:23715933

  5. Childhood depression: pharmacological therapy/treatment (pharmacotherapy of childhood depression).

    PubMed

    Wagner, K D; Ambrosini, P J

    2001-03-01

    Critiqued the published double-blind, placebo-controlled studies of antidepressant pharmacotherapy in child and adolescent major depressive disorder to assess their overall efficacy. The pharmacological mechanism of antidepressant action also was discussed. At best, antidepressant treatment for depressed youths is only modestly effective. In particular, the tricyclic antidepressants are not superior to placebo; however, early evidence with the selective serotonin reuptake inhibitors is more encouraging. The theoretical basis for this response pattern is discussed from a methodological perspective, from a neurodevelopmental status, and from a biological viewpoint. Study modifications are suggested which could improve some of the methodological limitations apparent in previous clinical drug trials. PMID:11294082

  6. Pharmacologic approaches for the treatment of chronic insomnia.

    PubMed

    Neubauer, David N

    2003-01-01

    Insomnia is a common problem that for many sufferers persists chronically and may result from a wide range of causes. Specific treatments address particular underlying medical disorders. General therapeutic approaches, including pharmacologic and behavioral strategies, may have broad applicability to insomnia patients. Many different medications and substances have been used in an attempt to improve sleep. This article reviews the advantages and disadvantages of medications and other substances employed to promote improved sleep. Special emphasis is given to the use of the newer-generation benzodiazepine receptor agonist hypnotics. PMID:14626538

  7. Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment

    PubMed Central

    Azevedo, Paula S.; Polegato, Bertha F.; Minicucci, Marcos F.; Paiva, Sergio A. R.; Zornoff, Leonardo A. M.

    2016-01-01

    Cardiac remodeling is defined as a group of molecular, cellular and interstitial changes that manifest clinically as changes in size, mass, geometry and function of the heart after injury. The process results in poor prognosis because of its association with ventricular dysfunction and malignant arrhythmias. Here, we discuss the concepts and clinical implications of cardiac remodeling, and the pathophysiological role of different factors, including cell death, energy metabolism, oxidative stress, inflammation, collagen, contractile proteins, calcium transport, geometry and neurohormonal activation. Finally, the article describes the pharmacological treatment of cardiac remodeling, which can be divided into three different stages of strategies: consolidated, promising and potential strategies. PMID:26647721

  8. Adding a treatment arm to an ongoing clinical trial: a review of methodology and practice.

    PubMed

    Cohen, Dena R; Todd, Susan; Gregory, Walter M; Brown, Julia M

    2015-01-01

    Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised. It may take many years to run a clinical trial from concept to reporting within a rapidly changing drug development environment; hence, in order for trials to be most useful to inform policy and practice, it is advantageous for them to be able to adapt to emerging therapeutic developments. This paper reports a comprehensive literature review on methodologies for, and practical examples of, amending an ongoing clinical trial by adding a new treatment arm. Relevant methodological literature describing statistical considerations required when making this specific type of amendment is identified, and the key statistical concepts when planning the addition of a new treatment arm are extracted, assessed and summarised. For completeness, this includes an assessment of statistical recommendations within general adaptive design guidance documents. Examples of confirmatory ongoing trials designed within the frequentist framework that have added an arm in practice are reported; and the details of the amendment are reviewed. An assessment is made as to how well the relevant statistical considerations were addressed in practice, and the related implications. The literature review confirmed that there is currently no clear methodological guidance on this topic, but that guidance would be advantageous to help this efficient design amendment to be used more frequently and appropriately in practice. Eight confirmatory trials were identified to have added a treatment arm, suggesting that trials can benefit from this amendment and that it can be practically feasible; however, the trials were not always able to address the key statistical considerations

  9. [Statement about diagnosis assessment ano non pharmacological treatment of obesity].

    PubMed

    Manrique E, Mónica; de la Maza, María Pía; Carrasco, Fernando; Moreno, Manuel; Albala, Cecilia; García, Jaime; Díaz, Jaime; Liberman, Claudio

    2009-07-01

    The risk of complications of obesity is proportional to body mass index and is higher in severe or morbid obesities and when abdominal or visceral fat is predominant. In Chile the prevalence of obesity is increasing. According to the World Health Organization, obese subjects must reduce at least a 5% of their weight to reduce the risk of complications. Although this amount of reduction is seldom achieved with non pharmacological treatments, better results are obtained with multidisciplinary/ approaches that include a medical, psychosocial and laboratory assessment, to determine obesity level and different factors involved and the associated complications. In a second stage, goals of treatment are set and a personalized treatment is designed including dietary changes and physical activity. The aim is to obtain perdurable lifestyles modifications. PMID:19802427

  10. Use of quantitative pharmacology tools to improve malaria treatments.

    PubMed

    Davis, Timothy M E; Moore, Brioni R; Salman, Sam; Page-Sharp, Madhu; Batty, Kevin T; Manning, Laurens

    2016-01-01

    The use of pharmacokinetic (PK) and pharmacodynamic (PD) data to inform antimalarial treatment regimens has accelerated in the past few decades, due in no small part to the stimulus provided by progressive development of parasite resistance to most of the currently available drugs. An understanding of the disposition, interactions, efficacy and toxicity of the mainstay of contemporary antimalarial treatment, artemisinin combination therapy (ACT), has been facilitated by PK/PD studies which have been used to refine treatment regimens across the spectrum of disease, especially in special groups including young children and pregnant women. The present review highlights recent clinically-important examples of the ways in which these quantitative pharmacology tools have been applied to improve ACT, as well as 8-aminoquinoline use and the characterisation of novel antimalarial therapies such as the spiroindolones. PMID:26652110

  11. The evidence-based pharmacological treatment of social anxiety disorder.

    PubMed

    Blanco, Carlos; Raza, Muhammad S; Schneier, Franklin R; Liebowitz, Michael R

    2003-12-01

    Social anxiety disorder (SAD) is a highly prevalent and often disabling disorder. This paper reviews the pharmacological treatment of SAD based on published placebo-controlled studies and published meta-analyses. It addresses three specific questions: What is the first-line treatment of SAD? How long should treatment last? What should be the management of treatment-resistant cases? Based on their efficacy for SAD and common comorbid disorders, tolerability, and safety, SSRIs should be considered as the first-line treatment for most patients. Less information is available regarding the optimal length of treatment, although individuals who discontinue treatment after 12-20 wk appear more likely to relapse than those who continue on medication. Even less empirical evidence is available to support strategies for treatment-resistant cases. Clinical experience suggests that SSRI non-responders may benefit from augmentation with benzodiazepines or gabapentin, or from switching to MAOIs, RIMAs, benzodiazepines or gabapentin. Cognitive-behavioural therapy may also be a helpful adjunct or alternative. PMID:14609440

  12. Pharmacologic Treatment for Pediatric Gastroparesis: A Review of the Literature

    PubMed Central

    Smetana, Keaton S.; Bantu, Likeselam; Buckley, Merrion G.

    2016-01-01

    There have been a number of agents that have been tried for treatment of gastroparesis over the past 3 decades, with varying levels of success. Guidelines exist for the management of gastroparesis in adults; however, even though the cause of gastroparesis in children is similar to that in adults, no guidelines exist for treating pediatric gastroparesis as studies on the topic are limited. With what little information we have on pediatric gastroparesis, medications used in children's studies do not seem to demonstrate the same results as in adult patients with gastroparesis; thus, future studies of whether certain medications are effective for treating pediatric gastroparesis and at what dose still need to be conducted. Pharmacological treatment options for pediatric gastroparesis do not show a clear correlation of resolving or even maintaining gastroparesis-associated symptoms or disease state. This article reviews the available studies of drugs that have shown some efficacy, with an emphasis on pediatric studies. PMID:27199619

  13. Non-pharmacologic treatment of insomnia in persons with dementia.

    PubMed

    Shub, Denis; Darvishi, Roham; Kunik, Mark E

    2009-02-01

    The prevalence of insomnia increases with age and affects up to 35% of community-dwelling adults with dementia. Sleep disturbances and associated cognitive and behavioral symptoms in this patient population can be a significant contributor to morbidity, mortality, and caregiver burden. Despite the frequency with which sleep disorders are encountered in primary care, few evidence-based guidelines are available to guide physician treatment plans. Sedative-hypnotic medications are commonly prescribed but are associated with significant adverse effects and have limited efficacy data. Non-pharmacologic treatments can be safe and effective adjuncts or alternatives to medications but are often underused in clinical practice. This article reviews practical applications of modalities such as light therapy, exercise, and sleep-hygiene modification in treating insomnia in persons with dementia. PMID:19256583

  14. Pharmacologic Treatment for Pediatric Gastroparesis: A Review of the Literature.

    PubMed

    Tillman, Emma M; Smetana, Keaton S; Bantu, Likeselam; Buckley, Merrion G

    2016-01-01

    There have been a number of agents that have been tried for treatment of gastroparesis over the past 3 decades, with varying levels of success. Guidelines exist for the management of gastroparesis in adults; however, even though the cause of gastroparesis in children is similar to that in adults, no guidelines exist for treating pediatric gastroparesis as studies on the topic are limited. With what little information we have on pediatric gastroparesis, medications used in children's studies do not seem to demonstrate the same results as in adult patients with gastroparesis; thus, future studies of whether certain medications are effective for treating pediatric gastroparesis and at what dose still need to be conducted. Pharmacological treatment options for pediatric gastroparesis do not show a clear correlation of resolving or even maintaining gastroparesis-associated symptoms or disease state. This article reviews the available studies of drugs that have shown some efficacy, with an emphasis on pediatric studies. PMID:27199619

  15. [Indications and future perspectives in the pharmacological treatment of hypercortisolism].

    PubMed

    Stigliano, Antonio; Toscano, Vincenzo

    2016-03-01

    The hypercortisolism is a rare endocrine disease characterized by an autonomous steroid secretion or excessive adrenal stimulation by ACTH. the Surgical removal of the lesion directly responsible hypercortisolism represents the treatment of choice. When neurosurgery for pituitary adenoma is contraindicated, radiotherapy is candidate as the second line of therapy. Currently, the recent advances in medical therapy provide a viable alternative to surgery and radiotherapy, when these are not feasible or followed by relapses (present in more than one third of cases) of the underlying disease. Recently, also in Italy, are available pharmacological agents with central activity (pasireotide) specifically indicated for treating Cushing's disease together with peripherally acting drugs (metyrapone and ketoconazole) that are used in a broader spectrum of hypercortisolemic clinical pictures. In addition, drugs active in the inhibition of steroidogenesis provide a valid support to the patient's surgical preparation allowing the reduction or normalization of plasma cortisol levels. PMID:27030224

  16. Current challenges and pitfalls in the pharmacological treatment of depression

    PubMed Central

    Popa-Velea, O; Gheorghe, IR; Truţescu, CI; Purcărea, VL

    2015-01-01

    The multifactorial etiology of depression obliges needs an individual assessment, the psychopharmacological approach involving a biopsychosocial analysis for each individual case. The rebalancing of the depressive patient, seen as a return to a normal level of psychosocial functioning and reduced risk of relapse is achieved with a prompt and constant support of specialized teams. Treatment should include psychopharmacological and psychosocial approaches, the results being interrelated and contributing to the prognosis of the disorder. Progress in clinical and pharmacological research, vivid dynamics of socio-economic environment, the complexity of diagnostic evaluation and the need for an interdisciplinary approach may cause difficulties in addressing the depressive patient and the ethical controversies. The aim of this paper is to present a brief analysis of challenges encountered in the present psychiatric practice, starting from the heterogeneity of depressive manifestations and finishing with the prioritization of interventional forms. PMID:25866576

  17. Alternative pharmacological strategies for adult ADHD treatment: a systematic review.

    PubMed

    Buoli, Massimiliano; Serati, Marta; Cahn, Wiepke

    2016-01-01

    Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder. PMID:26693882

  18. Current challenges and pitfalls in the pharmacological treatment of depression.

    PubMed

    Popa-Velea, O; Gheorghe, I R; Truţescu, C I; Purcărea, V L

    2015-01-01

    The multifactorial etiology of depression obliges needs an individual assessment, the psychopharmacological approach involving a biopsychosocial analysis for each individual case. The rebalancing of the depressive patient, seen as a return to a normal level of psychosocial functioning and reduced risk of relapse is achieved with a prompt and constant support of specialized teams. Treatment should include psychopharmacological and psychosocial approaches, the results being interrelated and contributing to the prognosis of the disorder. Progress in clinical and pharmacological research, vivid dynamics of socio-economic environment, the complexity of diagnostic evaluation and the need for an interdisciplinary approach may cause difficulties in addressing the depressive patient and the ethical controversies. The aim of this paper is to present a brief analysis of challenges encountered in the present psychiatric practice, starting from the heterogeneity of depressive manifestations and finishing with the prioritization of interventional forms. PMID:25866576

  19. Optimal Pharmacologic Treatment Strategies in Obesity and Type 2 Diabetes

    PubMed Central

    Goswami, Gayotri; Shinkazh, Nataliya; Davis, Nichola

    2014-01-01

    The prevalence of obesity has increased to pandemic levels worldwide and is related to increased risk of morbidity and mortality. Metabolic comorbidities are commonly associated with obesity and include metabolic syndrome, pre-diabetes, and type 2 diabetes. Even if the prevalence of obesity remains stable until 2030, the anticipated numbers of people with diabetes will more than double as a consequence of population aging and urbanization. Weight reduction is integral in the prevention of diabetes among obese adults with pre-diabetes. Lifestyle intervention and weight reduction are also key in the management of type 2 diabetes. Weight loss is challenging for most obese patients, but for those with diabetes, it can pose an even greater challenge due to the weight gain associated with many treatment regimens. This article will review optimal treatment strategies for patients with comorbid obesity and type 2 diabetes. The role of anti-obesity agents in diabetes will also be reviewed. This literature review will provide readers with current strategies for the pharmacologic treatment of obesity and diabetes with a focus on the weight outcomes related to diabetes treatments. PMID:26237392

  20. Treatment Approaches for Self-Injurious Behavior in Individuals with Autism: Behavioral and Pharmacological Methods

    ERIC Educational Resources Information Center

    Mahatmya, Duhita; Zobel, Alicia; Valdovinos, Maria G.

    2008-01-01

    This paper reviews behavioral and pharmacological approaches to the treatment of self-injurious behavior in autism. Both behavioral and pharmacological approaches offer a multitude of treatment options which we hope to elucidate. In providing this review, the goal is to provide an awareness of the treatment options available and to prompt further…

  1. Pharmacology of opioids in the treatment of chronic pain syndromes.

    PubMed

    Vallejo, Ricardo; Barkin, Robert L; Wang, Victor C

    2011-01-01

    The perpetual pursuit of pain elimination has been constant throughout human history and pervades human cultures. In some ways it is as old as medicine itself. Cultures throughout history have practiced the art of pain management through remedies such as oral ingestion of herbs or techniques believed to have special properties. In fact, even Hippocrates wrote about the practice of trepanation, the cutting of holes in the body to release pain. Current therapies for management of pain include the pervasive utilization of opioids, which have an extensive history, spanning centuries. There is general agreement about the appropriateness of opioids for the treatment of acute and cancer pain, but the long-term use of these drugs for treatment of chronic non-malignant pain remains controversial. The pros and cons regarding these issues are beyond the scope of this review. Instead, the purpose of this review will be directed towards the pharmacology of commonly prescribed opioids in the treatment of various chronic pain syndromes. Opium, derived from the Greek word for "juice," is extracted from the latex sap of the opium poppy (Papaverum somniferum). The juice of the poppy is the source of some 20 different alkaloids of opium. These alkaloids of opioids can be divided into 2 chemical classes: phenanthrenes (morphine, codeine, and thebaine) and benzylisoquinolines (agents that do not interact with opioid receptors). PMID:21785485

  2. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment

    PubMed Central

    Im, Sin-Hyeog; Barchan, Dora; Fuchs, Sara; Souroujon, Miriam C.

    1999-01-01

    Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR α-subunit (Hα1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Hα1-205–induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis. J. Clin. Invest. 104:1723–1730 (1999). PMID:10606626

  3. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment.

    PubMed

    Im, S H; Barchan, D; Fuchs, S; Souroujon, M C

    1999-12-01

    Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR alpha-subunit (Halpha1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Halpha1-205-induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis. PMID:10606626

  4. Fish oil–based lipid emulsions in the treatment of parenteral nutrition-associated liver disease: An ongoing positive experience

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutrition-associated liver disease (PNALD). In this report, we share our ongoing experience at Texas Children's Hospital, Houston, in the use of FOLE in treatment of P...

  5. Update on the Pharmacological Treatment of Alzheimer’s Disease

    PubMed Central

    Massoud, Fadi; Gauthier, Serge

    2010-01-01

    Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Worldwide prevalence of the disease is estimated at more than 24 million cases. With aging of populations, this number will likely increase to more than 80 million cases by the year 2040. The annual incidence worldwide is estimated at 4.6 million cases which is the equivalent of one new case every seven seconds! The pathophysiology of AD is complex and largely misunderstood. It is thought to start with the accumulation of beta-amyloid (Aβ) that leads to deposition of insoluble neuritic or senile plaques. Secondary events in this “amyloid cascade” include hyperphosphorylation of the protein tau into neurofibrillary tangles, inflammation, oxidation, and excitotoxicity that eventually cause activation of apoptotis, cell death and neurotransmitter deficits. This review will briefly summarize recent advances in the pathophysiology of AD and focus on the pharmacological treatment of the cognitive and functional symptoms of AD. It will discuss the roles of vascular prevention, cholinesterase inhibitors and an NMDA-antagonist in the management of AD. It will address the issues thought to be related to the lack of persistence or discontinuation of therapy with cholinesterase inhibitors shown in recent studies and some of the solutions proposed. These include setting realistic expectations in light of a neurodegenerative condition and available symptomatic treatments, slowly titrating medications, and using alternate routes of administration. Finally, it will introduce future therapeutic options currently under study. PMID:20808547

  6. Recent advances in pharmacological treatment of irritable bowel syndrome

    PubMed Central

    Lazaraki, Georgia; Chatzimavroudis, Grigoris; Katsinelos, Panagiotis

    2014-01-01

    Irritable bowel syndrome (IBS) is a highly prevalent functional disorder that reduces patients’ quality of life. It is a chronic disorder characterized by abdominal pain or discomfort associated with disordered defecation in the absence of identifiable structural or biochemical abnormalities. IBS imposes a significant economic burden to the healthcare system. Alteration in neurohumoral mechanisms and psychological factors, bacterial overgrowth, genetic factors, gut motility, visceral hypersensitivity, and immune system factors are currently believed to influence the pathogenesis of IBS. It is possible that there is an interaction of one or more of these etiologic factors leading to heterogeneous symptoms of IBS. IBS treatment is predicated upon the patient’s most bothersome symptoms. Despite the wide range of medications and the high prevalence of the disease, to date no completely effective remedy is available. This article reviews the literature from January 2008 to July 2013 on the subject of IBS peripherally acting pharmacological treatment. Drugs are categorized according to their administration for IBS-C, IBS-D or abdominal pain predominant IBS. PMID:25083060

  7. Treatment of schizophrenia and comorbid substance abuse: pharmacologic approaches.

    PubMed

    Green, Alan I

    2006-01-01

    Co-occurring substance use disorder is common among patients with schizophrenia, and its presence greatly worsens the course of schizophrenia. A number of theories have been introduced to explain the increased rate of substance use disorder in these patients. These theories include the notion that substance use could trigger psychotic symptoms in vulnerable individuals and the idea that the substances are used to self-medicate symptoms of schizophrenia. Our group and others have advanced a neurobiological hypothesis to explain this comorbidity-that a mesocorticolimbic brain reward circuit underlies the substance use disorder in patients with schizophrenia. Treatment of substance use disorder in these patients is best done with integrated treatment programs that combine psychosocial interventions with pharmacotherapy. Recent data suggest that the atypical antipsychotic clozapine and perhaps other atypical agents may lessen substance use in patients with schizophrenia. My colleagues and I have proposed that clozapine's effect in these patients may be related to its ability to decrease the brain reward circuit dysfunction. Research is continuing on the use of atypical antipsychotics in patients with schizophrenia and comorbid substance abuse. The adjunctive use of naltrexone or other agents also may be helpful. Further research on the optimal pharmacologic approach to patients with dual diagnosis is needed. PMID:16961422

  8. Non-pharmacological approaches to the treatment of narcolepsy.

    PubMed

    Garma, L; Marchand, F

    1994-12-01

    A way of evaluating the part played by non-drug treatments is to study cases of patients who discontinued stimulant medications but still came back for follow-up visits. Out of 40 patients with narcolepsy-cataplexy, three refused medication because their work was compatible with a regimen of naps (follow-up 1 year), and 10 stopped taking drugs when they could adapt nap therapy to a new life-style (follow-up 6.9 +/- 5 years). Three interrelated levels of non-pharmacological treatments of narcolepsy were examined: 1) Behavioral management, which includes: (A) structured sleep schedules: literature shows that a single long afternoon nap proffered greatest performance benefits in reaction time, significantly increased over a no-nap control condition, with no evidence of sleep inertia. The placement of this nap might yield better results if scheduled 1 hour before that of a normal subject. (B) Dietary factors: little is known about the effects of diet in narcoleptics; however, avoiding simple sugars will improve alertness in some patients. 2) Medical and psychiatric aspects of care. 3) Social factors as an interface between the patients and their environment. PMID:7701208

  9. Pharmacological treatment of acute migraine in adolescents and children.

    PubMed

    Wöber-Bingöl, Çiçek

    2013-06-01

    Migraine is a common disease in children and adolescents. The incidence of migraine has increased alarmingly in the general population during recent decades. Migraine causes considerable individual suffering and impaired quality of life. Therefore, appropriate management is essential. In this article, the treatment of acute migraine in children and adolescents will be reviewed. Only a few randomized controlled studies have been published and high placebo rates are a major problem for proving superiority of active drugs. Generally, acetaminophen (paracetamol) and ibuprofen are accepted as drugs of first choice, even though the evidence is poor for the former and limited for latter. Among 14 studies on triptans in adolescents, 9 showed some superiority over placebo with respect to pain relief and pain freedom, and among 6 studies in children, 5 suggest some superiority over placebo. Sumatriptan nasal spray and zolmitriptan nasal spray have been approved for adolescents in Europe; almotriptan has been approved for adolescents in the USA, as has rizatriptan for patients aged 6-17 years. A recent study demonstrated the efficacy of a fixed combination of sumatriptan and naproxen in adolescents with migraine. In conclusion, evidence for the pharmacological treatment of acute migraine in children is very poor and evidence for adolescents is better but still limited. PMID:23575981

  10. Pharmacologic approaches to treatment resistant depression: Evidences and personal experience

    PubMed Central

    Tundo, Antonio; de Filippis, Rocco; Proietti, Luca

    2015-01-01

    AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression (TRD) and to discuss them according to personal clinical experience. METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries (PubMed, Google Scholar e Quertle Searches) using terms: “treatment resistant depression”, “treatment refractory depression”, “partial response depression”, “non responder depression”, “optimization strategy”, “switching strategy”, “combination strategy”, “augmentation strategy”, selective serotonin reuptake inhibitors antidepressants (SSRI), tricyclic antidepressants (TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant (MAOI), lithium, thyroid hormones, second generation antipsychotics (SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy: (1) switching from an ineffective antidepressant (AD) to a new AD from a similar or different class; (2) combining the current AD regimen with a second AD from a different class; and (3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself. RESULTS: Switching from a TCA to another TCA provides only a modest advantage (response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous (response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine (5 positive trials out 6), TCA (2 positive trials out 3), and MAOI (2 positive trials out

  11. Non-pharmacological medical treatment in pediatric epilepsies.

    PubMed

    Auvin, S

    2016-03-01

    The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet that has been employed as a non-pharmacologic therapy for refractory epilepsy. Several multicenter and two randomized studies have demonstrated the efficacy of the ketogenic diet and the modified Atkins diet for children and adolescent with pharmacoresitant epilepsy. In order to facilitate patient tolerability and palatability, the diet protocols are gradually modified including changes in ratios of the fat versus non-fat components and the initiation of the diet with or without fasting. The modified Atkins diet is now used as an alternative diet. A randomized trial establishing the efficacy of the modified Atkins diet is now available. More recently, the low glycemic index diet seems to be used successfully for pharmacoresistant epilepsy but there are currently only open studies. Looking at the clinical efficacy of dietary treatments, the studies usually report a greater than 50% reduction in seizure frequency in about half of patients at 3 months under diet. Most of the patients who are responders to the ketogenic diet exhibited a decrease in seizure frequency within two months of treatment onset. Efficacy of the ketogenic diet has also been reported for teenager and adult patients. Dietary treatment of epilepsy should not be considered as a last chance treatment. It can be used during the investigation for epilepsy surgery even in case of structural abnormalities. In some epilepsy syndromes such as infantile spasms, myoclonic-astatic epilepsy and refractory status epilepticus, an early use seems helpful. The exact underlying mechanisms are unknown and remain a topic of active research. PMID:26993568

  12. New pharmacologic horizons in the treatment of Parkinson disease.

    PubMed

    Bonuccelli, Ubaldo; Del Dotto, Paolo

    2006-10-10

    Many of the motoric features that define Parkinson's disease (PD) result primarily from the loss of dopaminergic neurons of the substantia nigra. l-dopa remains at present the most powerful symptomatic drug for the treatment of this condition. However, motor complications of chronic l-dopa treatment have emerged as a major limitation of this therapy. Slowing or delaying the progression of the disease with neuroprotective therapies may delay the need for l-dopa. In the past few years, novel insight into the pathogenetic mechanisms of neurodegeneration in PD has been provided. Mitochondrial function deficiency, increased oxidative stress, apoptosis, excitotoxicity, and inflammation are part of the processes that ultimately result in neurodegeneration. Drugs that are now under clinical scrutiny as neuroprotectant include molecules that combine one or more of the following properties: (1) monoamine oxidase inhibition (rasagiline, safinamide); (2) mitochondrial enhancement (coenzyme Q10, creatine); (3) antiapoptotic activity; (4) anti-inflammatory activity; (5) protein aggregation inhibition; (6) neurotrophic activity. In advanced Parkinson's disease, the combination of disease progression and l-dopa therapy leads to the development of motor response complications, particularly wearing off, on off, dyskinesias and dystonias. The nonphysiologic pulsatile stimulation of striatal dopamine receptors, produced by the currently available dopaminergic drugs, may trigger a dysregulation of many neurotransmitter systems within the basal ganglia, mainly localized on medium spiny striatal neurons. These include alterations of glutamatergic, serotonergic, adrenergic and adenosine A(2A) receptors. Novel strategies for pharmacological intervention with nondopaminergic treatments hold the promise of providing effective control or reversal of motor response complications. Of particular interest are NMDA and AMPA antagonists or drugs acting on 5-HT subtype 2A, alpha2-adrenergic, and

  13. Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics.

    PubMed

    Alda, M

    2015-06-01

    After decades of research, the mechanism of action of lithium in preventing recurrences of bipolar disorder remains only partially understood. Lithium research is complicated by the absence of suitable animal models of bipolar disorder and by having to rely on in vitro studies of peripheral tissues. A number of distinct hypotheses emerged over the years, but none has been conclusively supported or rejected. The common theme emerging from pharmacological and genetic studies is that lithium affects multiple steps in cellular signaling, usually enhancing basal and inhibiting stimulated activities. Some of the key nodes of these regulatory networks include GSK3 (glycogen synthase kinase 3), CREB (cAMP response element-binding protein) and Na(+)-K(+) ATPase. Genetic and pharmacogenetic studies are starting to generate promising findings, but remain limited by small sample sizes. As full responders to lithium seem to represent a unique clinical population, there is inherent value and need for studies of lithium responders. Such studies will be an opportunity to uncover specific effects of lithium in those individuals who clearly benefit from the treatment. PMID:25687772

  14. Emerging pharmacologic treatment options for fragile X syndrome

    PubMed Central

    Schaefer, Tori L; Davenport, Matthew H; Erickson, Craig A

    2015-01-01

    Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and autism spectrum disorder. Caused by a silenced fragile X mental retardation 1 gene and the subsequent deficiency in fragile X mental retardation protein, patients with FXS experience a range of physical, behavioral, and intellectual debilitations. The FXS field, as a whole, has recently met with some challenges, as several targeted clinical trials with high expectations of success have failed to elucidate significant improvements in a variety of symptom domains. As new clinical trials in FXS are planned, there has been much discussion about the use of the commonly used clinical outcome measures, as well as study design considerations, patient stratification, and optimal age range for treatment. The evidence that modification of these drug targets and use of these failed compounds would prove to be efficacious in human clinical study were rooted in years of basic and translational research. There are questions arising as to the use of the mouse models for studying FXS treatment development. This issue is twofold: many of the symptom domains and molecular and biochemical changes assessed and indicative of efficacy in mouse model study are not easily amenable to clinical trials in people with FXS because of the intolerability of the testing paradigm or a lack of noninvasive techniques (prepulse inhibition, sensory hypersensitivity, startle reactivity, or electrophysiologic, biochemical, or structural changes in the brain); and capturing subtle yet meaningful changes in symptom domains such as sociability, anxiety, and hyperactivity in human FXS clinical trials is challenging with the currently used measures (typically parent/caregiver rating scales). Clinicians, researchers, and the pharmaceutical industry have all had to take a step back and critically evaluate the way we think about how to best optimize future investigations into pharmacologic FXS treatments. As new clinical

  15. Pharmacologic Treatment of Dimensional Anxious Depression: A Review

    PubMed Central

    Niciu, Mark J.; Richards, Erica M.; Zarate, Carlos A.

    2014-01-01

    Objective: To review the pharmacologic treatment of dimensionally defined anxious depression. Data Sources: English-language, adult human research articles published between 1949 and February 2013 were identified via PUBMED and EMBASE. The search term was treatment of anxious depression. Study Selection: We identified and reviewed 304 original articles. Of these, 31 studies of patients with anxious depression, who were treated with an antidepressant or antipsychotic, are included in this review. Data Extraction: All studies explicitly used a dimensional definition of anxious depression. All patients were treated with either antidepressants or antipsychotic medications. Results: Of the 31 relevant psychopharmacologic studies identified, 7 examined patients receiving only 1 medication, 2 studied cotherapeutic strategies, 1 examined antipsychotic augmentation, and 21 compared multiple medications. Eleven were pooled analyses from several studies. All studies were of adults (18–92 years old). The Hamilton Depression Rating Scale Anxiety/Somatization Factor Score was used to define anxious depression in 71% of the studies, and 77.4% were post hoc analyses of previous datasets. Seventeen studies found selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and/or tricyclic antidepressants (TCAs) to be useful for successfully treating anxious depression. However, patients with anxious depression were less likely to experience sustained response or remission. Furthermore, baseline anxious depression puts patients at greater risk for side effect burden. Conclusions: Despite achieving response with SSRIs, SNRIs, and TCAs, patients with dimensionally defined anxious depression do not maintain response or remission and often report a larger burden of side effects compared to nonanxious depressive patients, suggesting that it is a harder-to-treat subtype of major depressive disorder. PMID:25317369

  16. Children with schizophrenia: clinical picture and pharmacological treatment.

    PubMed

    Masi, Gabriele; Mucci, Maria; Pari, Cinzia

    2006-01-01

    these clinical patterns, such as multidimensionally impaired disorder and multiple complex developmental disorder. In the context of a multimodal approach, including behavioral, social, scholastic and familial interventions, a pharmacological treatment is usually the core treatment. Available experience from the few controlled studies, open studies and case reports on pharmacotherapy in children with schizophrenia aged <12 years is critically analysed in this review, with particular reference to the use of atypical antipsychotics in clinical practice. To date, the major evidence supports the efficacy of risperidone and olanzapine, while clozapine seems an effective option in treatment-refractory cases. Published experience with newer atypical antipsychotics (quetiapine, ziprasidone, aripiprazole) is still lacking in this age range. Safety data (namely extrapyramidal symptoms, weight gain, hyperprolactinaemia, haematological adverse effects, seizures, hepatotoxicity, metabolic effects, neuroleptic malignant syndrome and cardiovascular effects) are reviewed and discussed, along with strategies for management. PMID:16999454

  17. The effect of pharmacological treatment on gait biomechanics in peripheral arterial disease patients

    PubMed Central

    2010-01-01

    Background Pharmacological treatment has been advocated as a first line therapy for Peripheral Arterial Disease (PAD) patients suffering from intermittent claudication. Previous studies document the ability of pharmacological treatment to increase walking distances. However, the effect of pharmacological treatment on gait biomechanics in PAD patients has not been objectively evaluated as is common with other gait abnormalities. Methods Sixteen patients were prescribed an FDA approved drug (Pentoxifylline or Cilostazol) for the treatment of symptomatic PAD. Patients underwent baseline gait testing prior to medication use which consisted of acquisition of ground reaction forces and kinematics while walking in a pain free state. After three months of treatment, patients underwent repeat gait testing. Results Patients with symptomatic PAD had significant gait abnormalities at baseline during pain free walking as compared to healthy controls. However, pharmacological treatment did not produce any identifiable alterations on the biomechanics of gait of the PAD patients as revealed by the statistical comparisons performed between pre and post-treatment and between post-treatment and the healthy controls. Conclusions Pharmacological treatment did not result in statistically significant improvements in the gait biomechanics of patients with symptomatic PAD. Future studies will need to further explore different cohorts of patients that have shown to improve significantly their claudication distances and/or their muscle fiber morphology with the use of pharmacological treatment and determine if this is associated with an improvement in gait biomechanics. Using these methods we may distinguish the patients who benefit from pharmacotherapy and those who do not. PMID:20529284

  18. Pharmacologic and surgical treatment of dyslipidemic children and adolescents.

    PubMed

    Hoeg, J M

    1991-01-01

    A wide variety of treatment modalities have been used in children with dyslipidemias to reduce the concentrations of atherogenic lipoprotein particles. Most of the published experience has focused upon children with familial hypercholesterolemia (FH). A variety of pharmacologic regimens have been utilized with variable degrees of success. The bile acid sequestrants colestipol and cholestyramine, lovastatin, pantethine, paraminosalicylic acid, and fenofibrate have all been successful in reducing total blood cholesterol concentrations by 18-24% in hypercholesterolemic children. Of these medications, only the bile acid sequestrants are not absorbed into the circulation. This theoretic advantage is paralled by long-term safety studies which indicate the absence of serious adverse effects with bile acid sequestrant therapy. Therefore, the bile acid sequestrants represent the drugs of choice in treating severely dyslipidemic children. In selected cases of profoundly dyslipidemic children, other therapeutic strategies have been utilized. Most of these efforts have been directed in the treatment of the child homozygous for FH. Despite the lipid lowering effects of partial ileal bypass surgery in hypercholesterolemic adults, homozygous familial hypercholesterolemic children are not adequately treated by this approach. Portacaval shunt has reduced the total cholesterol concentrations by 20-35% in homozygous FH children without having a negative impact on growth and development. These children have, however, gone on to develop atherosclerotic cardiovascular disease despite therapy. Liver transplantation has led to virtual normalization of the plasma lipoprotein concentrations in 3 children homozygous for familial hypercholesterolemia, and there is evidence for regression of vascular lesions in the coronary arteries in one of these children. However, considering the expense, the difficulty in posttransplantation management, and the irreversible nature of the therapy, liver

  19. Prevention and treatment of traveler's diarrhea: a clinical pharmacological approach.

    PubMed

    Scarpignato, C; Rampal, P

    1995-01-01

    Diarrhea represents a major health problem for travelers to developing countries. Although the syndrome is usually self-limited and recovery occurs in the majority of cases without any specific form of therapy, there is a need for safe and effective ways of preventing and treating it. Since the syndrome is most often caused by an infection acquired by ingesting fecally contaminated food or beverages, precautions regarding dietary habits remain the cornerstone of prophylaxis, but dietary self-restrictions do not always translate to reduced rates of diarrheal illness. Administration of probiotics (e.g. lactobacilli or Saccharomyces boulardii) and immunoprophylaxis with the newer oral cholera vaccines have been tried with promising results. Antimicrobials remain, however, the most successful form of prophylaxis, being effective in up to 90% of travelers. For those with impaired health who will take prophylaxis, systemic agents with proved efficacy should be recommended. For other otherwise healthy persons, poorly absorbed agents are preferable in order to avoid the serious, albeit rare, toxicity of systemic drugs. The key factor in the management of acute watery traveler's diarrhea, particularly in infants and young children, is the restoration of water and electrolyte balance. This does not reduce the duration of the illness but will limit dehydration and prevent acidosis. Many patients will require no additional therapy, whereas some will need pharmacologic treatment to shorten the duration of diarrhea or to relieve the accompanying symptoms, like abdominal discomfort, nausea and vomiting. A typical 3- to 5-day illness can be reduced to approximately 1 day by trimethoprim-sulfamethoxazole (TMP-SMX) combination. Some other systemic antimicrobials have been successfully used but, during the last few years, the 4-fluoroquinolone drugs have received considerable attention and have been shown to be highly effective in reducing the duration of traveler's diarrhea. These

  20. Behavioral, Cognitive, and Pharmacological Treatments of Panic Disorder with Agoraphobia: Critique and Synthesis.

    ERIC Educational Resources Information Center

    Michelson, Larry K.; Marchione, Karen

    1991-01-01

    Examines theoretical, methodologic, and research issues as well as strengths, limitations, and possible interactions pertaining to behavioral, cognitive, and pharmacological treatments of panic disorder with agoraphobia. Compares attrition, outcome, and maintenance effects and presents composite indices of significant improvement, endstate…

  1. Soft tissue infection caused by Legionella bozemanii in a patient with ongoing immunosuppressive treatment

    PubMed Central

    Neiderud, Carl-Johan; Vidh, Angela Lagerqvist; Salaneck, Erik

    2013-01-01

    The Legionellaceae family consists of approximately 50 species, of which the most commonly identified species is L. pneumophila, the causative agent of Legionnaires’ disease. Other Legionella ssp. most often cause clinical infections in the immune-compromised patients, in which L. bozemanii has been known to cause both pneumonia and lung abscesses. In the presented case, a soft tissue infection in a patient with ongoing immunosuppression was determined to be due to L. bozemanii. Hence, in immune-deficient patients, L. bozemanii could be considered a possible agent in soft tissue infections when other common pathogens have been ruled out. PMID:24023988

  2. The effect of childhood trauma on pharmacological treatment response in depressed inpatients.

    PubMed

    Douglas, Katie M; Porter, Richard J

    2012-12-30

    Childhood trauma and its association with pharmacological treatment response were examined in depressed inpatients. Treatment non-responders (n=31) reported significantly more severe trauma than treatment responders (n=25) and healthy controls (n=49), suggesting that the experience of childhood trauma in those hospitalised with depression can be detrimental to treatment success. PMID:22770764

  3. More ubiquitous effects from non-pharmacologic than from pharmacologic treatments for fibromyalgia syndrome: a meta-analysis examining six core symptoms.

    PubMed

    Perrot, S; Russell, I J

    2014-09-01

    This study aimed to characterize and compare the efficacy profile on six fibromyalgia syndrome (FM) core symptoms associated with pharmacologic and non-pharmacologic treatments. We screened PubMed, Embase and the Cochrane Library for FM articles from 1990 to September 2012 to analyse randomized controlled trials comparing pharmacologic or non-pharmacologic treatments to placebo or sham. Papers including assessments of at least 2 of the 6 main FM symptom domains - pain, sleep disturbance, fatigue, affective symptoms (depression/anxiety), functional deficit and cognitive impairment - were selected for analysis. Studies exploring pharmacologic approaches (n = 21) were mainly dedicated to treating a small number of dimensions, mostly pain. They were of good quality but were not prospectively designed to simultaneously document efficacy for the management of multiple core FM symptom domains. Only amitriptyline demonstrated a significant effect on as many as three core FM symptoms, but it exhibited many adverse effects and was subject to early tachyphylaxis. Studies involving non-pharmacologic approaches (n = 64) were typically of poorer quality but were more often dedicated to multidimensional targets. Pool therapy demonstrated significant effects on five symptom domains, repetitive transcranial magnetic stimulation on four domains, balneotherapy on three domains and exercise, cognitive behaviour therapy and massage on two domains each. Differences between pharmacologic and non-pharmacologic approaches may be related to different modes of action, tolerability profiles and study designs. Very few drugs in well-designed clinical trials have demonstrated significant relief for multiple FM symptom domains, whereas non-pharmacologic treatments with weaker study designs have demonstrated multidimensional effects. Future therapeutic trials for FM should prospectively examine each of the core domains and should attempt to combine pharmacologic and non-pharmacologic

  4. Treatment of ongoing autoimmune encephalomyelitis with activated B-cell progenitors maturing into regulatory B cells.

    PubMed

    Korniotis, Sarantis; Gras, Christophe; Letscher, Hélène; Montandon, Ruddy; Mégret, Jérôme; Siegert, Stefanie; Ezine, Sophie; Fallon, Padraic G; Luther, Sanjiv A; Fillatreau, Simon; Zavala, Flora

    2016-01-01

    The influence of signals perceived by immature B cells during their development in bone marrow on their subsequent functions as mature cells are poorly defined. Here, we show that bone marrow cells transiently stimulated in vivo or in vitro through the Toll-like receptor 9 generate proB cells (CpG-proBs) that interrupt experimental autoimmune encephalomyelitis (EAE) when transferred at the onset of clinical symptoms. Protection requires differentiation of CpG-proBs into mature B cells that home to reactive lymph nodes, where they trap T cells by releasing the CCR7 ligand, CCL19, and to inflamed central nervous system, where they locally limit immunopathogenesis through interleukin-10 production, thereby cooperatively inhibiting ongoing EAE. These data demonstrate that a transient inflammation at the environment, where proB cells develop, is sufficient to confer regulatory functions onto their mature B-cell progeny. In addition, these properties of CpG-proBs open interesting perspectives for cell therapy of autoimmune diseases. PMID:27396388

  5. Pharmacologic options for the treatment and management of food allergy.

    PubMed

    Kobernick, Aaron K; Chambliss, Jeffrey; Burks, A Wesley

    2015-01-01

    Food allergy affects approximately 5% of adults and 8% of children in developed countries, and there is currently no cure. Current pharmacologic management is limited to using intramuscular epinephrine or oral antihistamines in response to food allergen exposure. Recent trials have examined the efficacy and safety of subcutaneous, oral, sublingual, and epicutaneous immunotherapy, with varying levels of efficacy and safety demonstrated. Bacterial adjuvants, use of anti-IgE monoclonal antibodies, and Chinese herbal formulations represent exciting potential for development of future pharmacotherapeutic agents. Ultimately, immunotherapy may be a viable option for patients with food allergy, although efficacy and safety are likely to be less than ideal. PMID:26289224

  6. Ongoing Inquiry

    ERIC Educational Resources Information Center

    Ashbrook, Peggy

    2011-01-01

    An in-depth science inquiry is an ongoing investigation in which children are introduced to materials through hands-on experiences and, with teacher guidance, begin to investigate a question that they can answer through their own actions, observations, and with teacher-assisted research. Qualities that make an experience appropriate to include in…

  7. Pharmacological Treatment of Attention Deficit Hyperactivity Disorder in Children and Adolescents: Clinical Strategies

    PubMed Central

    Shier, Anna C.; Reichenbacher, Thomas; Ghuman, Harinder S.; Ghuman, Jaswinder K.

    2013-01-01

    Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder of childhood that can result in significant functional impairment, and if not adequately treated can lead to impaired quality of life. Pharmacotherapy is considered the first-line treatment for ADHD in children and adolescents. We review both recent literature and seminal studies regarding the pharmacological treatment of ADHD in children and adolescents. There is ample evidence for the efficacy and safety of both stimulants and non-stimulants in the treatment of ADHD. We review important aspects of evaluation and assessment and discuss first-line pharmacological treatments and as well as when to consider using alternative pharmacological agents. Treatment approaches to manage frequently seen comorbid disorders with ADHD are also covered. PMID:23650474

  8. Treatment of hemophilia: a review of current advances and ongoing issues

    PubMed Central

    Coppola, Antonio; Di Capua, Mirko; Di Minno, Matteo Nicola Dario; Di Palo, Mariagiovanna; Marrone, Emiliana; Ieranò, Paola; Arturo, Claudia; Tufano, Antonella; Cerbone, Anna Maria

    2010-01-01

    Replacement of the congenitally deficient factor VIII or IX through plasma-derived or recombinant concentrates is the mainstay of treatment for hemophilia. Concentrate infusions when hemorrhages occur typically in joint and muscles (on-demand treatment) is able to resolve bleeding, but does not prevent the progressive joint deterioration leading to crippling hemophilic arthropathy. Therefore, primary prophylaxis, ie, regular infusion of concentrates started after the first joint bleed and/or before the age of two years, is now recognized as first-line treatment in children with severe hemophilia. Secondary prophylaxis, whenever started, aims to avoid (or delay) the progression of arthropathy and improve patient quality of life. Interestingly, recent data suggest a role for early prophylaxis also in preventing development of inhibitors, the most serious complication of treatment in hemophilia, in which multiple genetic and environmental factors may be involved. Treatment of bleeds in patients with inhibitors requires bypassing agents (activated prothrombin complex concentrates, recombinant factor VIIa). However, eradication of inhibitors by induction of immune tolerance should be the first choice for patients with recent onset inhibitors. The wide availability of safe factor concentrates and programs for comprehensive care has now resulted in highly satisfactory treatment of hemophilia patients in developed countries. Unfortunately, this is not true for more than two-thirds of persons with hemophilia, who live in developing countries. PMID:22282697

  9. Pharmacological Approaches in the Treatment and Maintenance of Weight Loss.

    PubMed

    Van Gaal, Luc; Dirinck, Eveline

    2016-08-01

    Obesity is a growing global health concern, associated with a number of important comorbid conditions. It increases the risk of diabetes and contributes to development of cardiovascular disease. While the benefits of weight loss are well established, weight reduction remains a difficult-to-reach goal in overweight and obese individuals due to several metabolic and psychological factors. For many patients, lifestyle intervention is insufficient to achieve long-term weight loss, and additional options, such as pharmacotherapy, need to be considered. Besides the challenging enterprise of weight reduction, weight maintenance remains an even more crucial and outcome-determining aspect of weight management. This article focuses on the potential of currently available pharmacological strategies to support weight loss and maintenance goals in individuals at risk. Two pharmacotherapy types are considered: those developed primarily to induce weight loss and those developed primarily for blood glucose control that have a favorable effect on body weight. Finally, the potential of very low- and low-calorie diets combined with pharmacotherapy and pharmacological combination therapies are discussed, as well as emerging approaches in development. PMID:27440841

  10. Current and emerging pharmacological treatments for sarcoidosis: a review

    PubMed Central

    Beegle, Scott H; Barba, Kerry; Gobunsuy, Romel; Judson, Marc A

    2013-01-01

    The treatment of sarcoidosis is not standardized. Because sarcoidosis may never cause significant symptoms or organ dysfunction, treatment is not mandatory. When treatment is indicated, oral corticosteroids are usually recommended because they are highly likely to be effective in a relative short period of time. However, because sarcoidosis is often a chronic condition, long-term treatment with corticosteroids may cause significant toxicity. Therefore, corticosteroid sparing agents are often indicated in patients requiring chronic therapy. This review outlines the indications for treatment, corticosteroid treatment, and corticosteroid sparing treatments for sarcoidosis. PMID:23596348

  11. [Pharmacological treatment of substance dependence from a neuroscientific perspective (I): opiates and cocaine].

    PubMed

    Haro, G; Cervera, G; Martínez-Raga, J; Pérez-Gálvez, B; Fernández-Garcés, M; Sanjuan, J

    2003-01-01

    In this review paper it is intended to analyze the most recent publications on pharmacological treatment of drug dependences from a neuroscientific perspective. It has been divided into two parts, the first one focuses on the treatment of illegal substance dependence, specifically opiates and cocaine; and the second part deals with the pharmacological treatments of three substances, two legal drugs such as alcohol and tobacco, and a group of medications with abuse potential, benzodiazepines. In this first part the neuroscientific aspects (genetic, neurochemistry, circuits involved, neuroimaging and neuropsychological deficits) relevant to understanding the pharmacological treatment of the main drug addictions are summarized. The pharmacotherapies of opiate dependence, both for detoxification and for dehabituation, are then discussed. Finally, the main medications that have been proposed to treat cocaine dependence are also reviewed. PMID:12838444

  12. Hemisphere Asymmetry of Response to Pharmacologic Treatment in an Alzheimer's Disease Mouse Model.

    PubMed

    Manousopoulou, Antigoni; Saito, Satoshi; Yamamoto, Yumi; Al-Daghri, Nasser M; Ihara, Masafumi; Carare, Roxana O; Garbis, Spiros D

    2016-01-01

    The aim of this study was to examine hemisphere asymmetry of response to pharmacologic treatment in an Alzheimer's disease mouse model using cilostazol as a chemical stimulus. Eight-month-old mice were assigned to vehicle or cilostazol treatment for three months and hemispheres were analyzed using quantitative proteomics. Bioinformatics interpretation showed that following treatment, aggregation of blood platelets significantly decreased in the right hemisphere whereas neurodegeneration significantly decreased and synaptic transmission increased in the left hemisphere only. Our study provides novel evidence on cerebral laterality of pharmacologic activity, with important implications in deciphering regional pharmacodynamic effects of existing drugs thus uncovering novel hemisphere-specific therapeutic targets. PMID:26836196

  13. Dental ethics case 6. Stalled payment for ongoing orthodontic treatment--balancing responsibilities.

    PubMed

    Doyal, L; Naidoo, S

    2010-10-01

    It is not always easy for an orthodontist to strike the right balance between a caring, supportive and patient-centered approach, and the need to make a living and to run a profitable business in order to achieve this. Striving to act ethically and professionally at all times will help find this elusive balance and ultimately it will be more rewarding and professionally satisfying. Especially when dealing with children whose lives may be dramatically affected by the interruption or cessation of treatment, orthodontists have a duty to reassure themselves about the financial stability of their contractual relationships with patients or parents. Having consistent financial policies and flexible payment options may assist in this regard. Even in the face of non-payment of fees, treatments that have begun must in some form continue if their cessation would compromise the best interests of patients. PMID:21180294

  14. Partners' Ongoing Treatment for Chronic Disease and the Risk of Psychological Distress after the Great East Japan Earthquake.

    PubMed

    Nakaya, Naoki; Narita, Akira; Tsuchiya, Naho; Nakamura, Tomohiro; Tsuji, Ichiro; Hozawa, Atsushi; Tomita, Hiroaki

    2016-01-01

    Several studies have reported that not only patients with chronic diseases but also their partners are likely to face major psychosocial problems. This study examined the association between a partner's ongoing treatment for chronic disease and the risk of psychological distress after the Great East Japan Earthquake (GEJE). In 2012, a questionnaire was distributed as part of a cross-sectional study of participants aged 20 years or older living in a municipality that had been severely inundated by the tsunami following the GEJE. We identified couples using the household numbers of the municipality and collected self-reported information on ongoing chronic disease treatment for stroke, cancer, myocardial infarction, and angina. Psychological distress was evaluated using the Kessler 6 scale (K6) and was defined as a score ≥ 5/24 points. Among 1,246 couples (2,492 participants) thus identified, 2,369 completed the K6. The number of participants whose partners were under treatment for chronic diseases was 209 (9%). Overall, participants with partners who were receiving treatment for chronic diseases (odds ratio [OR] = 1.3, 95% confidence interval [CI] = 0.95-1.8, P = 0.09) did not show a significantly higher risk of psychological distress using logistic regression analysis. Women, but not men, whose partners were receiving treatment for chronic diseases, had a higher risk of psychological distress (women: OR = 1.6, P = 0.02; men: OR = 1.0, P = 0.92). After the GEJE, only in women the presence of partners under treatment for chronic diseases appears to be a risk factor for psychological distress. PMID:27506650

  15. Non-Pharmacological Treatments for ADHD in Youth

    PubMed Central

    Sharma, Anup; Gerbarg, Patricia L.; Brown, Richard P.

    2016-01-01

    Background Complementary and alternative medicine (CAM) in psychiatry or integrative psychiatry covers a wide range of biological, psychological and mind-body treatments that enhance standard medical practices and patient outcomes. While CAM approaches are popular amongst patients in their practice as well as in self-report because of their ease of use, health professionals have received limited education in these interventions and often are unaware of their patients’ use of CAM treatments. Method This overview highlights evidence-based CAM treatments for attention deficit hyperactivity disorder (ADHD) including dietary interventions, phytomedicines, mind-body practices and neurofeedback. Results While conventional treatments are the mainstays for ADHD, there are a large number of available treatments that can be used to enhance treatment response. Conclusion With improved education and further scientific and clinical research, validated integrative treatments will provide more effective, lower risk and lower cost care for patients with ADHD. PMID:27489754

  16. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

    PubMed Central

    de Kleine, Rianne A.; Rothbaum, Barbara O.; van Minnen, Agnes

    2013-01-01

    There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: d-cycloserine, MDMA, hydrocortisone, and propranolol. PMID:24147208

  17. Behavioral and emerging pharmacologic treatment options for cognitive impairment in schizophrenia.

    PubMed

    Vinogradov, Sophia; Schulz, S Charles

    2016-02-01

    In recent years, the goal of treatment for individuals with schizophrenia has shifted from symptom control to functional recovery. For recovery to occur, the substantial cognitive impairments associated with this disorder must be addressed. Advances in neuroscience have paved the way for the development of more effective behavioral and pharmacologic treatments. Behavioral interventions such as cognitive training are tapping into the innate plasticity and adaptive qualities of the brain. Emerging pharmacologic treatments are targeting new neurotransmitters and systems, such as the glutamatergic system and the nicotinic-cholinergic system, which are involved in the cognitive and sensory deficits that lead to impairment. The best chances for recovery will most likely occur by combining behavioral and pharmacologic interventions. PMID:26919053

  18. Pharmacological treatment of laser eye injuries by neuroprotection

    NASA Astrophysics Data System (ADS)

    Solberg, Yoram; Rosner, Mordechai; Belkin, Michael

    1996-04-01

    Many retinal injuries result in an irreversible neuronal loss, which can not yet be reduced by pharmacological methods. To determine whether glutamate-receptor blockers can serve as neuroprotective agents in the retina, as they do in the central nervous system, we examined the effects of MK-801, an NMDA-receptor antagonist, on laser-induced retinal injury in a rat model. Immediately and 8 h after argon laser retinal photocoagulation, rats were treated with intraperitoneal injections of MK-801 (3 mg/kg) or saline. After 3, 20 or 60 days the animals were sacrificed and their retinal lesions were evaluated histologically and morphometrically. Photoreceptor cell loss, both immediately and up to 2 months after laser irradiation, was significantly smaller in MK-801-treated rats than controls. MK-801 exhibits neuroprotective property in the retina. This points to the involvement of glutamate in the laser-induced retinal neuronal damage. Glutamate-receptor blockers should be further investigated for therapy of retinal diseases characterized by neuronal cell destruction.

  19. Delayed Cytotoxic T Lymphocyte-Associated Protein 4-Immunoglobulin Treatment Reverses Ongoing Alloantibody Responses and Rescues Allografts From Acute Rejection.

    PubMed

    Young, J S; Chen, J; Miller, M L; Vu, V; Tian, C; Moon, J J; Alegre, M-L; Sciammas, R; Chong, A S

    2016-08-01

    Antibody-mediated rejection has emerged as the leading cause of late graft loss in kidney transplant recipients, and inhibition of donor-specific antibody production should lead to improved transplant outcomes. The fusion protein cytotoxic T lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocks T cell activation and consequently inhibits T-dependent B cell antibody production, and the current paradigm is that CTLA4-Ig is effective with naïve T cells and less so with activated or memory T cells. In this study, we used a mouse model of allosensitization to investigate the efficacy of continuous CTLA4-Ig treatment, initiated 7 or 14 days after sensitization, for inhibiting ongoing allospecific B cell responses. Delayed treatment with CTLA4-Ig collapsed the allospecific germinal center B cell response and inhibited alloantibody production. Using adoptively transferred T cell receptor transgenic T cells and a novel approach to track endogenous graft-specific T cells, we demonstrate that delayed CTLA4-Ig minimally inhibited graft-specific CD4(+) and T follicular helper responses. Remarkably, delaying CTLA4-Ig until day 6 after transplantation in a fully mismatched heart transplant model inhibited alloantibody production and prevented acute rejection, whereas transferred hyperimmune sera reversed the effects of delayed CTLA4-Ig. Collectively, our studies revealed the unexpected efficacy of CTLA4-Ig for inhibiting ongoing B cell responses even when the graft-specific T cell response was robustly established. PMID:26928966

  20. Current Concepts and Ongoing Research in the Prevention and Treatment of Open Fracture Infections

    PubMed Central

    Hannigan, Geoffrey D.; Pulos, Nicholas; Grice, Elizabeth A.; Mehta, Samir

    2015-01-01

    Significance: Open fractures are fractures in which the bone has violated the skin and soft tissue. Because of their severity, open fractures are associated with complications that can result in increased lengths of hospital stays, multiple operative interventions, and even amputation. One of the factors thought to influence the extent of these complications is exposure and contamination of the open fracture with environmental microorganisms, potentially those that are pathogenic in nature. Recent Advances: Current open fracture care aims to prevent infection by wound classification, prophylactic antibiotic administration, debridement and irrigation, and stable fracture fixation. Critical Issues: Despite these established treatment paradigms, infections and infection-related complications remain a significant clinical burden. To address this, improvements need to be made in our ability to detect bacterial infections, effectively remove wound contamination, eradicate infections, and treat and prevent biofilm formation associated with fracture fixation hardware. Future Directions: Current research is addressing these critical issues. While culture methods are of limited value, culture-independent molecular techniques are being developed to provide informative detection of bacterial contamination and infection. Other advanced contamination- and infection-detecting techniques are also being investigated. New hardware-coating methods are being developed to minimize the risk of biofilm formation in wounds, and immune stimulation techniques are being developed to prevent open fracture infections. PMID:25566415

  1. Pharmacological treatments for obsessive-compulsive disorder in children and adolescents: a qualitative review.

    PubMed

    Rosa-Alcázar, Ana I; Iniesta-Sepúlveda, Marina; Rosa-Alcázar, Angel

    2013-01-01

    We present the results of a systematic review on the effectiveness of pharmacological treatments for children and adolescents with obsessive-compulsive disorder. Sixty-four studies fulfilled the selection criteria, being the most of them focused in SSRI and Clomipramine. The trials on augmentation strategies and third line monotherapies are scarce, being the majority open-trials and case series. Similarly, studies on combined treatment (psychological and pharmacological) are few; furthermore this is a relevant future research line. It is also remarkable the lack of quasi-experimental and experimental comparison studies and the long-term follow-up measures. PMID:23803803

  2. Role of "old" pharmacological agents in the treatment of Cushing's syndrome.

    PubMed

    Ambrogio, A G; Cavagnini, F

    2016-09-01

    Despite recent advances in the management of endogenous Cushing's syndrome (CS), its treatment remains a challenge. When surgery has been unsuccessful or unfeasible as well in case of recurrence, the "old" pharmacological agents represent an important alternative for both ACTH-dependent and independent hypercortisolism. Especially in the latter, the advent of novel molecules directly targeting ACTH secretion has not outweighed the "old" drugs, which continue to be largely employed and have recently undergone a reappraisal. This review provides a survey of the "old" pharmacological agents in the treatment of CS. PMID:27086313

  3. Adherence to Pharmacological Treatment for Juvenile Bipolar Disorder

    ERIC Educational Resources Information Center

    Drotar, Dennis; Greenley, Rachel Neff; Demeter, Christine A.; McNamara, Nora K.; Stansbrey, Robert J.; Calabrese, Joseph R.; Stange, Jonathan; Vijay, Priya; Findling, Robert L.

    2007-01-01

    Objective: The objective of this study was to describe the prevalence and correlates of adherence to divalproex sodium (DVPX) and lithium carbonate (Li) combination treatment during the initial stabilization treatment phase. Method: Adherence to Li/DVPX combination therapy was measured by the presence or absence of minimum serum concentrations of…

  4. Pharmacological treatment of migraine during pregnancy and breastfeeding.

    PubMed

    Amundsen, Siri; Nordeng, Hedvig; Nezvalová-Henriksen, Kateřina; Stovner, Lars Jacob; Spigset, Olav

    2015-04-01

    Migraine affects up to 25% of women of reproductive age. In the majority of these women, migraine improves progressively during pregnancy, but symptoms generally recur shortly after delivery. As suboptimally treated migraine in pregnancy could have negative consequences for both mother and fetus, the primary aim of clinicians should be to provide optimal treatment according to stage of pregnancy, while minimising possible risks related to drug therapy. Nonpharmacological approaches are always first-line treatment, and should also be used to complement any required drug treatment. Paracetamol is the preferred drug for acute treatment throughout pregnancy. If paracetamol is not sufficiently effective, sporadic use of sumatriptan can be considered. NSAIDs such as ibuprofen can also be used under certain circumstances, though their intake in the first and third trimesters is associated with specific risks and contraindications. Preventive treatment should only be considered in the most severe cases. In women contemplating pregnancy, counselling is essential to promote a safe and healthy pregnancy and postpartum period for the mother and child, and should involve a dialogue addressing maternal concerns and expectations about drug treatment. This Review summarizes current evidence of the safety of the most common antimigraine medications during pregnancy and breastfeeding, and provides treatment recommendations for use in clinical practice. PMID:25776823

  5. Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence.

    PubMed

    Sinclair, Julia M A; Chambers, Sophia E; Shiles, Celia J; Baldwin, David S

    2016-07-01

    Alcohol use disorders (AUD) cause significant morbidity and mortality worldwide, but pharmacological treatments for them are underused, despite evidence of efficacy. Acamprosate, naltrexone, nalmefene and disulfiram are all approved in one or more region for the treatment of AUD. Baclofen currently has a temporary indication in France. Safety considerations for using psychopharmacological treatments in this patient group include the impact of concurrent alcohol consumption at high levels; multiple physical comorbidities that may interfere with pharmacological effects, distribution and metabolism; and concomitant medication for the treatment of comorbid physical and psychiatric conditions. The five drugs, including an extended-release injectable suspension of naltrexone, have different safety profiles that need to be balanced with the treatment objective (initiation or continuation of abstinence, or reduction of drinking), individual patient preferences and comorbid conditions. Appropriate treatment will be based on the unique risk-benefit profile in each case. PMID:27023898

  6. [Pharmacological treatment of other types of secondary osteoporosis].

    PubMed

    Okazaki, Ryo

    2015-10-01

    This article reviews the treatment strategy for the secondary osteoporosis excluding those caused by diabetes, CKD, endocrine disorders, or glucocorticoid, which proceeding articles deal with. Among numerous possible causes for such secondary osteoporosis, the author has selected osteogenesis imperfecta (OI), osteoporosis associated with gastrectomy or bariatric surgery, inflammatory bowel diseases (IBD), and chronic obstructive pulmonary disease (COPD). For OI, current standard treatment is bisphosphonates (BPs), of which efficacy for fracture inhibition has recently been of issue. Other treatment modalities, e.g. PTH, have just been explored. Osteoporosis associated with gastrectomy, bariatric surgery or IBD, have been treated with vitamin D, calcium, and BPs. Despite high fracture rates, there are almost no treatment data for osteoporosis associated with COPD. PMID:26529940

  7. Pharmacological approaches to the challenge of treatment-resistant depression.

    PubMed

    Ionescu, Dawn F; Rosenbaum, Jerrold F; Alpert, Jonathan E

    2015-06-01

    Although monoaminergic antidepressants revolutionized the treatment of Major Depressive Disorder (MDD) over a half-century ago, approximately one third of depressed patients experience treatment-resistant depression (TRD). Such patients account for a disproportionately large burden of disease, as evidenced by increased disability, cost, human suffering, and suicide. This review addresses the definition, causes, evaluation, and treatment of unipolar TRD, as well as the major treatment strategies, including optimization, augmentation, combination, and switch therapies. Evidence for these options, as outlined in this review, is mainly focused on large-scale trials or meta-analyses. Finally, we briefly review emerging targets for antidepressant drug discovery and the novel effects of rapidly acting antidepressants, with a focus on ketamine. PMID:26246787

  8. Pharmacological approaches to the challenge of treatment-resistant depression

    PubMed Central

    Ionescu, Dawn F.; Rosenbaum, Jerrold F.; Alpert, Jonathan E.

    2015-01-01

    Although monoaminergic antidepressants revolutionized the treatment of Major Depressive Disorder (MDD) over a half-century ago, approximately one third of depressed patients experience treatment-resistant depression (TRD). Such patients account for a disproportionately large burden of disease, as evidenced by increased disability, cost, human suffering, and suicide. This review addresses the definition, causes, evaluation, and treatment of unipolar TRD, as well as the major treatment strategies, including optimization, augmentation, combination, and switch therapies. Evidence for these options, as outlined in this review, is mainly focused on large-scale trials or meta-analyses. Finally, we briefly review emerging targets for antidepressant drug discovery and the novel effects of rapidly acting antidepressants, with a focus on ketamine. PMID:26246787

  9. Pharmacological Approaches for Treatment-resistant Bipolar Disorder.

    PubMed

    Hui Poon, Shi; Sim, Kang; Baldessarini, Ross J

    2015-01-01

    Bipolar disorder is prevalent, with high risks of disability, substance abuse and premature mortality. Treatment responses typically are incomplete, especially for depressive components, so that many cases can be considered "treatment resistant." We reviewed reports on experimental treatments for such patients: there is a striking paucity of such research, mainly involving small incompletely controlled trials of add-on treatment, and findings remain preliminary. Encouraging results have been reported by adding aripiprazole, bupropion, clozapine, ketamine, memantine, pramipexole, pregabalin, and perhaps tri-iodothyronine in resistant manic or depressive phases. The urgency of incomplete responses in such a severe illness underscores the need for more systematic, simpler, and better controlled studies in more homogeneous samples of patients. PMID:26467409

  10. Pharmacological Approaches for Treatment-resistant Bipolar Disorder

    PubMed Central

    Poon, Shi Hui; Sim, Kang; Baldessarini, Ross J.

    2015-01-01

    Bipolar disorder is prevalent, with high risks of disability, substance abuse and premature mortality. Treatment responses typically are incomplete, especially for depressive components, so that many cases can be considered “treatment resistant.” We reviewed reports on experimental treatments for such patients: there is a striking paucity of such research, mainly involving small incompletely controlled trials of add-on treatment, and findings remain preliminary. Encouraging results have been reported by adding aripiprazole, bupropion, clozapine, ketamine, memantine, pramipexole, pregabalin, and perhaps tri-iodothyronine in resistant manic or depressive phases. The urgency of incomplete responses in such a severe illness underscores the need for more systematic, simpler, and better controlled studies in more homogeneous samples of patients. PMID:26467409

  11. The pharmacological treatment of opioid addiction--a clinical perspective.

    PubMed

    Lobmaier, Philipp; Gossop, Michael; Waal, Helge; Bramness, Jorgen

    2010-06-01

    This article reviews the main pharmacotherapies that are currently being used to treat opioid addiction. Treatments include detoxification using tapered methadone, buprenorphine, adrenergic agonists such as clonidine and lofexidine, and forms of rapid detoxification. In opioid maintenance treatment (OMT), methadone is most widely used. OMT with buprenorphine, buprenorphine-naloxone combination, or other opioid agonists is also discussed. The use of the opioid antagonists naloxone (for the treatment of intoxication and overdose) and oral and sustained-release formulations of naltrexone (for relapse prevention) is also considered. Although recent advances in the neurobiology of addictions may lead to the development of new pharmacotherapies for the treatment of addictive disorders, a major challenge lies in delivering existing treatments more effectively. Pharmacotherapy of opioid addiction alone is usually insufficient, and a complete treatment should also include effective psychosocial support or other interventions. Combining pharmacotherapies with psychosocial support strategies that are tailored to meet the patients' needs represents the best way to treat opioid addiction effectively. PMID:20169438

  12. Pharmacological treatment of catarrh in Iranian traditional medicine

    PubMed Central

    Choopani, Rasool; Sadr, Saeed; Kaveh, Shahpar; Kaveh, Narges; Dehghan, Sohrab

    2015-01-01

    Catarrh is a condition that is carefully explained in Iranian traditional medicine. Medieval Iranian physicians used some medicinal plants in the treatment of the catarrh. Some of these substances are used in treatment today, although still more of these materials can be used in modern medicine. In this study we searched known sources of Iranian traditional medicine and collected the ideas of former great scholars and physicians about medicinal plants that are used for treatment of catarrh. Then we searched PubMed, Google Scholar, Scopus, and Web of Science databases and found 10 medicinal herbs that have the ability to treat catarrh. Plants discussed in this study are consistent with new research and can be used in modern treatments. According to rising bacterial resistance to antibiotics and complications of antibiotic and anti-inflammatory drugs, it seems that the various components of the medicinal herbs can be beneficial in producing new drugs. Also it is hoped that more investigations on medicinal plants will be conducted in the future treatment of catarrh and other diseases related to it. PMID:26151014

  13. Pharmacologic Therapies in Women's Health: Contraception and Menopause Treatment.

    PubMed

    Allen, Caitlin; Evans, Ginger; Sutton, Eliza L

    2016-07-01

    Female hormones play a significant role in the etiology and treatment of many women's health conditions. This article focuses on the common uses of hormonal therapy. When prescribing estrogen-containing regimens throughout the span of a woman's life, the risks are similar (ie, cardiovascular risk and venous thromboembolism), but the degree of risk varies significantly depending on a woman's particular set of risk factors and the details of the hormone regimen. In addition to estrogens and progestogens, this article also touches on the use of selective steroid receptor modulators in emergency contraception and in treatment of menopause symptoms. PMID:27235614

  14. Psychophysiological Outcome of Behavioral and Pharmacological Treatments of Agoraphobia.

    ERIC Educational Resources Information Center

    Michelson, Larry; Mavissakalian, Matig

    1985-01-01

    Examined relative and combined effectiveness of behavior therapy and pharmacotherapy in 62 severe, chronic agoraphobics. Identified differential temporal response and treatment patterns across psychophysiological domains. Synchrony/desynchrony phenomena yielded significant findings with regard to process and clinical outcome status. Exploratory…

  15. Current status of pharmacological treatment of colorectal cancer

    PubMed Central

    Akhtar, Reyhan; Chandel, Shammy; Sarotra, Pooja; Medhi, Bikash

    2014-01-01

    AIM: To review the clinical trials for the development in drugs for chemotherapeutic treatment of colorectal cancer (CRC). METHODS: A systematic review identified randomized controlled trials (RCTs) assessing drugs for the treatment of CRC or adenomatous polyps from www.clinicaltrials.gov. Various online medical databases were searched for relevant publications. RESULTS: Combination treatment regimens of standard drugs with newer agents have been shown to improve overall survival, disease-free survival, time to progression and quality of life compared to that with standard drugs alone in patients with advanced colorectal cancer. The FOLFOXIRI regimen has been associated with a significantly higher response rate, progression-free survival and overall survival compared to the FOLFIRI regimen. CONCLUSION: Oxaliplatin plus intravenous bolus fluorouracil and leucovorin has been shown to be superior for disease-free survival when compared to intravenous bolus fluorouracil and leucovorin. In addition, oxaliplatin regimens were more likely to result in successful surgical resections. First line treatment with cetuximab plus fluorouracil, leucovorin and irinotecan has been found to reduce the risk of metastatic progression in patients with epidermal growth factor receptor-positive colorectal cancer with unresectable metastases. The addition of bevacizumab has been shown to significantly increase overall and progression-free survival when given in combination with standard therapy. PMID:24936228

  16. Pharmacologically assisted treatment of opioid-dependent youth.

    PubMed

    Pecoraro, Anna; Fishman, Marc; Ma, Michelle; Piralishvili, Gvantsa; Woody, George E

    2013-12-01

    Opioid misuse, abuse, and dependence are global problems whose patterns vary across cultures. In the USA, the non-medical use of prescription opioids has become particularly serious because of its association with addiction and overdose death. Agonist and antagonist medications have been shown to be effective for opioid-dependent adults, and there is a growing body of data that they are also effective for youth. Here, we summarize evidence that detoxification alone results in high rates of treatment dropout and relapse but that the limited but growing data on the extended use of medication-assisted treatment for opioid-dependent youth have been positive. The implementation of medication-assisted treatment as a standard practice is feasible, easily integrated with counseling or psychotherapy, and has potential to greatly improve outcomes. Although concerns about safety and efficacy with youth require more research, and we do not advocate indefinite maintenance, we suggest that opioid-dependent youth should be considered as candidates for medication-assisted treatment delivered in a comprehensive, developmentally appropriate context, beginning at the first episode of care, with the strength of the recommendation to use medication increasing with each care episode. PMID:23912754

  17. Pharmacological Management of Treatment-Resistant Pediatric Depression

    ERIC Educational Resources Information Center

    Kratochvil, Christopher J.; Wagner, Karen Dineen; Emslie, Graham; March, John

    2005-01-01

    A 13-year-old boy presents with treatment-resistant symptoms of major depression. This is his first episode of depression, initially treated with 200 mg sertraline for 12 weeks with no significant benefit. The severe depression has shown a partial response to weekly cognitive-behavioral therapy (CBT) and fluoxetine, which was titrated up to 60 mg…

  18. Options for pharmacological treatment of refractory bipolar depression.

    PubMed

    Tondo, Leonardo; Vázquez, Gustavo H; Baldessarini, Ross J

    2014-02-01

    Bipolar disorders of types I and II, even when treated by currently standard options, show a marked excess of depressive morbidity. Treated, type I patients in mid-course or from the onset of illness are ill, overall, 50 % of weeks of follow-up, and 75 % of that unresolved morbidity is depressive. Currently widely held impressions are that bipolar depression typically is poorly responsive to antidepressants, that treatment-resistant depression (TRD) is characteristic of the disorder, and that risk of mania with antidepressant treatment is very high. However, none of these views is supported consistently by available research. TRD may be more prevalent in bipolar than unipolar mood disorders. Relatively intense research attention is directed toward characteristics and treatments of TRD in unipolar depression, but studies of bipolar TRD are uncommon. We found only five controlled trials, plus 10 uncontrolled trials, providing data on a total of 13 drug treatments, all of which involved one or two trials, in 87 % as add-ons to complex, uncontrolled regimens. In two controlled trials, ketamine was superior to placebo but it is short-acting and not orally active; pramipexole was weakly superior to placebo in one controlled trial; three other drugs failed to outperform controls. Other pharmacotherapies are inadequately evaluated and nonpharmacological options are virtually untested in bipolar TRD. The available research supports the view that antidepressants may be effective in bipolar depression provided that currently agitated patients are excluded, that risk of mania with antidepressants is only moderately greater than risk of spontaneous mania, and that bipolar TRD is not necessarily resistant to all treatments. PMID:24425269

  19. Approved and Off-Label Uses of Obesity Medications, and Potential New Pharmacologic Treatment Options

    PubMed Central

    Isidro, Maria Luisa; Cordido, Fernando

    2010-01-01

    Available anti-obesity pharmacotherapy options remain very limited and development of more effective drugs has become a priority. The potential strategies to achieve weight loss are to reduce energy intake by stimulating anorexigenic signals or by blocking orexigenic signals, and to increase energy expenditure. This review will focus on approved obesity medications, as well as potential new pharmacologic treatment options.

  20. Recovery of function in humans: Cortical stimulation and pharmacological treatments after stroke

    PubMed Central

    Floel, Agnes; Cohen, Leonardo G.

    2016-01-01

    In this contribution, we first provide an overview of general principles of reorganisation in the human brain, and point out possible biomarkers of recovery. Subsequently, we expand on possibilities of adjuvant therapy in human rehabilitation using cortical stimulation and pharmacological treatments. Finally, we suggest future directions for research in this field. PMID:19520165

  1. SMOKING CESSATION FOR ADOLESCENTS: A REVIEW OF PHARMACOLOGICAL AND PSYCHOSOCIAL TREATMENTS

    PubMed Central

    Schepis, TS; Rao, U

    2016-01-01

    Unlike the vast literature on smoking cessation in adults, research in adolescents has gained significant attention only within the last decade. Even with this increase in focus, research into pharmacological aids for smoking cessation in adolescents (e.g., nicotine replacement therapy, bupropion) is a more recent phenomenon and has produced only modest results. While more extensive, much of the research on behaviorally- or psychosocially-based adolescent smoking cessation interventions has been limited by a lack of control for contact time, biochemical verification of self-reported abstinence, and/or a theoretical focus for the interventions. The MEDLINE, PubMed, PSYCInfo CINHAL and Cochrane Systematic Review databases were searched for articles relevant to adolescent smoking cessation treatment. After briefly examining the adolescent smoking cessation research prior to 2000, more recent developments in pharmacological aids and psychological treatment will be reviewed. Investigations have made progress in elucidating efficacious treatments for adolescent smokers, but much work remains to be done in both pharmacological and non-pharmacological areas of treatment. With the current state of the literature as a guide, future directions for research into smoking cessation for adolescents will be proposed. PMID:19630713

  2. Commissioning Pharmacological Treatments for Drug Users: A Brief Review of the Evidence Base

    ERIC Educational Resources Information Center

    Keen, Jenny; Oliver, Philip

    2004-01-01

    Aims: To provide a brief review of relevant existing evidence regarding pharmacological treatment for drug users, in order to enable commissioners and service providers to make informed decisions that are evidence based wherever possible. Methods: The review process involved an examination of key reference texts and literature derived from…

  3. Pharmacological Treatment of Bipolar Disorder among Children and Adolescents

    PubMed Central

    Blader, Joseph C.; Kafantaris, Vivian

    2010-01-01

    Summary There is growing recognition that bipolar disorder (BD) frequently first presents in adolescence. Preadolescents with volatile behavior and severe mood swings also comprise a large group of patients whose difficulties may lie within the bipolar spectrum. However, the preponderance of scientific effort and clinical trials for this condition have focused on adults. This review summarizes the BD's complexity and diagnosis among young people. It proceeds to review the principles of pharmacotherapy, to assess current treatment options, and to highlight areas where evidence-based guidance is lacking. Recent developments have enlarged the range of potential treatments for BD. Nonetheless, differences in the phenomenology, course, and sequelae of BD among young people compel greater attention to the benefits and liabilities of therapy for those affected by this illness’ early onset. PMID:17341174

  4. Challenges in the pharmacological treatment of geriatric asthma.

    PubMed

    Agusta, Fabio; Battaglia, Salvatore; Benfante, Alida; Spatafora, Mario; Scichilone, Nicola

    2016-07-01

    Asthma in older populations is characterized by frequent comorbid conditions, which increase the risk of side effects and of detrimental interactions between respiratory and non-respiratory drugs. These observations lead to the need to manage asthma in older populations by applying a multidimensional assessment and a multidisciplinary treatment; therefore, we favor the use of the 'geriatric' term to define asthma in the elderly. Geriatric asthma is a complex disease, which may not necessarily imply that it is also complicated, although the two conditions may often coexist. On this basis, the switch from an organ-driven management to the holistic approach may be the key factor to attain optimal control of the disease in this age range. The current review discusses the age-related factors affecting asthma treatment in the oldest individuals, such as the comorbid conditions, and age-related changes of metabolism and excretion that can impair the efficacy and safety of drugs. PMID:26986042

  5. [Non-pharmacologic treatment of arterial hypertension in hemodialysis patients].

    PubMed

    Chazot, C; Charra, B

    2007-10-01

    High blood pressure in dialysis patients is related to extracellular volume excess and the related increase of systemic vascular resistances. Scribner has early described the treatment of hypertension with ultrafiltration and low salt diet, without any drugs. The dry weight method relies on the progressive reduction of the postdialysis body weight until blood pressure is normalized. Additional measures are needed such as low salt diet, neutral sodium balance during dialysis treatment, stop of antihypertensive drugs, adequate length of the dialysis session, and patient education. It may exist a lag time between the normalization of the extracellular volume and blood pressure. It is related to the correction of the hemodynamic consequences of the extracellular volume overload. Moreover, the dry weight may potentially vary in patients undergoing catabolic intercurrent events. The complications of these changes (severe hypertension, pulmonary oedema) must be anticipated by the nephrologist and the staff to avoid additional morbidity to the patient. PMID:18340684

  6. Update on the pharmacological treatment of adult myositis.

    PubMed

    Oddis, C V

    2016-07-01

    The management of patients with idiopathic inflammatory myopathy (IIM) remains a challenge given the systemic features beyond active myositis. That is, recognizing the inflammatory arthropathy, varying dermatomyositis rashes, and overt and occult features of interstitial lung disease in addition to myositis adds to the complexity of diagnosis and treatment of IIM. However, clinicians now have available many more immunosuppressive drugs as well as biologic agents for use in patients with myositis and other autoimmune diseases. Here, the use of these agents is reviewed and support based on available published literature is provided even though many studies have been small and results somewhat anecdotal. Glucocorticoids remain the initial treatment of choice in most instances and methotrexate and azathioprine are often used early in the treatment course. These agents are followed by other immunosuppressive drugs, for example mycophenolate mofetil, tacrolimus, cyclosporine and cyclophosphamide, some of which are used alone while combinations of these agents also provide an effective option. There is more rationale for the use of biologic agents such as rituximab from a mechanistic perspective and, given the incorporation of validated core set measures in assessing myositis patients, we can look forward to better designed clinical trials in the future. PMID:27098592

  7. Pharmacological approach of the treatment of drinking problems: a critical overview.

    PubMed

    Verbanck, P; Barrias, J; Besson, J; Borg, S

    1993-01-01

    Many pharmacological agents have been proposed for the treatment of drinking problems. However, there are many pitfalls in the assessment of the clinical interest of those drugs. In this paper, we propose a new classification of drugs of interest for treating alcohol abuse and related problems. We also review the major clinical studies about those pharmacological agents and discuss, through the studies about serotonergic agents, lithium salts, disulfiram and related compounds, some peculiar aspects of those trials that we think to be important to develop better strategies for the evaluation of pharmacotherapy of alcoholism. PMID:7748291

  8. Guanfacine Extended Release: A New Pharmacological Treatment Option in Europe.

    PubMed

    Huss, Michael; Chen, Wai; Ludolph, Andrea G

    2016-01-01

    Children/adolescents with attention-deficit/hyperactivity disorder (ADHD) may have a poor or inadequate response to psychostimulants or be unable to tolerate their side-effects; furthermore, stimulants may be inappropriate because of co-existing conditions. Only one non-stimulant ADHD pharmacotherapy, the noradrenaline transporter inhibitor atomoxetine, is currently approved for use in Europe. We review recent advances in understanding of the pathophysiology of ADHD with a focus on the roles of catecholamine receptors in context of the α2A-adrenergic receptor agonist guanfacine extended release (GXR), a new non-stimulant treatment option in Europe. Neuroimaging studies of children/adolescents with ADHD show impaired brain maturation, and structural and functional anomalies in brain regions and networks. Neurobiological studies in ADHD and medication response patterns support involvement of monoaminergic neurotransmitters (primarily dopamine and noradrenaline). Guanfacine is a selective α2A-adrenergic receptor agonist that has been shown to improve prefrontal cortical cognitive function, including working memory. The hypothesized mode of action of guanfacine centres on direct stimulation of post-synaptic α2A-adrenergic receptors to enhance noradrenaline neurotransmission. Preclinical data suggest that guanfacine also influences dendritic spine growth and maturation. Clinical trials have demonstrated the efficacy of GXR in ADHD, and it is approved as monotherapy or adjunctive therapy to stimulants in Canada and the USA (for children and adolescents). GXR was approved recently in Europe for the treatment of ADHD in children and adolescents for whom stimulants are not suitable, not tolerated or have been shown to be ineffective. GXR may provide particular benefit for children/adolescents who have specific co-morbidities such as chronic tic disorders or oppositional defiant disorder (or oppositional symptoms) that have failed to respond to first-line treatment

  9. Defense style in panic disorder before and after pharmacological treatment.

    PubMed

    Marchesi, Carlo; Parenti, Paola; Aprile, Sonia; Cabrino, Chiara; De Panfilis, Chiara

    2011-05-30

    Whether or not the use of maladaptive defense style is a trait, as opposed to a state dependent phenomenon, in panic disorder (PD) is a topic still very much up for debate. The aim of the study was to verify whether PD patients, both before and after treatment, used different defense style than the control group. Sixty-one PD patients (recruited from an original sample of 90 patients) and 64 healthy controls were evaluated against the Structured Clinical Interview for DSM-IV disorders, the Symptoms Check List-90, the Hamilton Rating Scales for Anxiety and for Depression and finally the Defense Style Questionnaire-40 (DSQ). The patients were treated with paroxetine or citalopram and were evaluated monthly for one year to assess the remission. The DSQ was re-administered to the patients at the end of the study. Before treatment, PD patients used more neurotic and immature forms of defense than controls. After treatment, those in remission used the same defense styles as the control group, whereas non-remitters still used more immature defenses. However, all the aforementioned difference disappeared, after excluding the effect of symptom severity. Our data supports the hypothesis that the use of maladaptive defenses might be the consequence of PD: when subjects fall ill, their capacity to use mature adaptive defenses may diminish, but when they recover their defensive style returns to a greater maturity. The present results are however limited by the dropout rate (one third of patients did not complete the study) and the use of just one questionnaire to evaluate the complexity of defense styles. PMID:20692044

  10. Advances in the pharmacological treatment of Graves' orbitopathy.

    PubMed

    Ruchała, Marek; Sawicka-Gutaj, Nadia

    2016-07-01

    Graves' orbitopathy has a deteriorating effect on patients' appearance and vision, thus significantly decreases their quality of life. A multidisciplinary team of endocrinologists, ophthalmologists, head and neck surgeons, nuclear medicine physicians, radiologists, and psychologists should constitute a standard health care team for those patients. It is vital that the therapy is based on an individual approach, with patients being well informed and involved in the decision-making process. Generally, traditional therapies include immunosuppression with steroids, orbital irradiation and surgical decompression. Novel treatment modalities include: biological agents, somatostatin analogs, antioxidants, methotrexate. Better insight into pathogenesis of Graves' orbitopathy is the only chance for targeted therapy development. PMID:26966785

  11. Pharmacological treatment options for mast cell activation disease.

    PubMed

    Molderings, Gerhard J; Haenisch, Britta; Brettner, Stefan; Homann, Jürgen; Menzen, Markus; Dumoulin, Franz Ludwig; Panse, Jens; Butterfield, Joseph; Afrin, Lawrence B

    2016-07-01

    Mast cell activation disease (MCAD) is a term referring to a heterogeneous group of disorders characterized by aberrant release of variable subsets of mast cell (MC) mediators together with accumulation of either morphologically altered and immunohistochemically identifiable mutated MCs due to MC proliferation (systemic mastocytosis [SM] and MC leukemia [MCL]) or morphologically ordinary MCs due to decreased apoptosis (MC activation syndrome [MCAS] and well-differentiated SM). Clinical signs and symptoms in MCAD vary depending on disease subtype and result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. In most cases, treatment of MCAD is directed primarily at controlling the symptoms associated with MC mediator release. In advanced forms, such as aggressive SM and MCL, agents targeting MC proliferation such as kinase inhibitors may be provided. Targeted therapies aimed at blocking mutant protein variants and/or downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies. Since clinicians are often underprepared to evaluate, diagnose, and effectively treat this clinically heterogeneous disease, we seek to familiarize clinicians with MCAD and review current and future treatment approaches. PMID:27132234

  12. Pharmacological options for the treatment of Tourette's disorder.

    PubMed

    Jiménez-Jiménez, F J; García-Ruiz, P J

    2001-01-01

    Tourette's disorder is a neuropsychiatric disorder characterised clinically by motor and vocal tics, which may be associated to conductual disorders such as obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD). Although the neurochemistry of Tourette's disorder is not well known, there are some effective therapies for tics, OCD and ADHD. However, these are not devoid of adverse effects. Tics only require treatment when they interfere with the functioning of the patient. If therapy is needed, monotherapy at the minimal effective dose is desirable, but some patients may require two or more drugs. The most frequently used drugs for tics are antipsychotics (mainly pimozide and haloperidol) and clonidine. The potential usefulness of atypical antipsychotic drugs (risperidone, olanzapine, clozapine, ziprasidone) and other dopaminergic drugs (fluphenazine, sulpiride, tiapride, metoclopramide, piquindone, tetrabenazine), clonazepam, calcium channel antagonists, botulinum toxin, dopamine agonists, selegiline, and other drugs is discussed. The drugs of choice for OCD in patients with Tourette's disorder are the selective serotonin reuptake inhibitors (SSRIs), although the tricyclic antidepressant clomiplamine, which inhibits both serotonin and noradrenaline uptake, has also been found to be useful. ADHD can be treated with some psychostimulants, mainly methylphenidate, although these drugs must be used with caution. Other potentially useful drugs for the treatment of ADHD in patients with Tourette's disorder are clonidine, guanfacine, selegiline, some tricyclic antidepressants, sertraline, pimozide and clonazepam. Finally, the potential value of some nonpharmacological therapies (hypnotherapy, biofeedback, conductual therapies, electroconvulsive therapy, acupuncture and surgery) is briefly reviewed. PMID:11772131

  13. The Pharmacological Options in the Treatment of Eating Disorders

    PubMed Central

    Milano, W.; De Rosa, M.; Milano, L.; Riccio, A.; Sanseverino, B.; Capasso, A.

    2013-01-01

    The eating disorders (DCA) are complex systemic diseases with high social impact, which tend to become chronic with significant medical and psychiatric comorbidities. The literature data showed that there is good evidence to suggest the use of SSRIs, particularly at high doses of fluoxetine, in the treatment of BN reducing both the crisis of binge that the phenomena compensates and reducing the episodes of binge in patients with BED in the short term. Also, the topiramate (an AED) showed a good effectiveness in reducing the frequency and magnitude of episodes of binge with body weight reduction, both in the BN that is in the therapy of BED. To date, modest data support the use of low doses of second-generation antipsychotics in an attempt to reduce the creation of polarized weight and body shapes, the obsessive component, and anxiety in patients with AN. Data in the literature on long-term drug treatment of eating disorders are still very modest. It is essential to remember that the pharmacotherapy has, however, a remarkable efficacy in treating psychiatric disorders that occur in comorbidity with eating disorders, such as mood disorders, anxiety, insomnia, and obsessive-compulsive personality disorders and behavior. PMID:23956871

  14. Suicidal Behavior in Mood Disorders: Response to Pharmacological Treatment.

    PubMed

    Tondo, Leonardo; Baldessarini, Ross J

    2016-09-01

    Suicidal behavior is strongly associated with depression, especially if accompanied by behavioral activation, dysphoria, or agitation. It may respond to some treatments, but the design of scientifically sound, ethical trials to test for therapeutic effects on suicidal behavior is highly challenging. In bipolar disorder, and possibly also unipolar major depression, an underprescribed medical intervention with substantial evidence of preventive effects on suicidal behavior is long-term treatment with lithium. It is unclear whether this effect is specifically antisuicidal or reflects beneficial effects of lithium on depression, mood instability, and perhaps aggression and impulsivity. Antisuicidal effects of anticonvulsant mood stabilizers (carbamazepine, lamotrigine, valproate) appear to be less than with lithium. Further evaluation is needed for potential antisuicidal effects of atypical antipsychotics with growing evidence of efficacy in depression, particularly acute bipolar depression, while generally lacking risk of inducing agitation, mania, or mood instability. Short-term and long-term value and safety of antidepressants are relatively secure for unipolar depression but uncertain and poorly tested for bipolar depression; their effects on suicidal risk in unipolar depression may be age-dependent. Sedative anxiolytics are virtually unstudied as regards suicidal risks. Adequate management of suicidal risks in mood disorder patients requires comprehensive, clinically skillful monitoring and timely interventions. PMID:27542851

  15. The Management and Outcomes of Pharmacological Treatments for Tinnitus

    PubMed Central

    Palumbo, Devon Beebe; Joos, Kathleen; Ridder, Dirk De; Vanneste, Sven

    2015-01-01

    Tinnitus, a phantom sensation experienced by people around the world, currently is endured without a known cure. Some find the condition tolerable, while others are tortured on a daily basis from the incessant phantom noises. For those who seek treatment, oftentimes, they have a comorbid condition (e.g., depression, anxiety, insomnia), which is treated pharmaceutically. These products aim to reduce the comorbities associated with tinnitus thereby minimizing the overall burden present. Because of the phantom nature of tinnitus, it is often compared to neurologic pain. Since pain can be managed with pharmaceutical options, it is reasonable to assume that similar agents might work to alleviate tinnitus. The effects of antidepressants, benzodiazepines, anticonvulsants, and glutamate antagonists are reviewed in this paper. Table 1 summarizes the pharmaceutical products discussed. Due to the variety of comorbid factors and potential causes of tinnitus, there may not be one pharmaceutical treatment that will combat every type of tinnitus. Nevertheless, a product that finally addresses the true cause of tinnitus, and not just its comorbidities, will benefit millions of people worldwide. PMID:26467416

  16. Pharmacological treatment of cognitive deficits in Alzheimer's disease.

    PubMed

    Brodaty, H; Ames, D; Boundy, K L; Hecker, J; Snowdon, J; Storey, E; Yates, M W

    2001-09-17

    Clinical trials and independent reviews support the use of cholinesterase inhibitors for treating the symptoms of patients with mild to moderate Alzheimer's disease (AD). Before initiating cholinesterase inhibitor therapy, patients should be thoroughly assessed, and the diagnosis confirmed, preferably by a specialist. Compliance with cholinesterase inhibitor therapy should be monitored and the response (in global, cognitive, functional and behavioural domains) reassessed after 2-3 months of treatment. Vitamin E may be protective against AD, and therapy with 1000 IU twice daily may be considered. There is insufficient evidence to support the use of other antioxidant agents, anti-inflammatory agents, monoamine oxidase B inhibitors, folate/homocysteine or antihypertensive drugs in patients with AD, or hormone replacement therapy in affected women. PMID:11665948

  17. Update on the Pharmacological Treatment of Pathological Gambling

    PubMed Central

    Bullock, Scott A.; Potenza, Marc N.

    2014-01-01

    This is an update to a previously published article discussing the neuropsychopharmacology of pathological gambling (PG) (1). In the prior manuscript, we described how cortico-limbic circuitry and neurotransmitter systems (norepinephrine, serotonin, dopamine, opioids, glutamate, and gamma-aminobutyric acid (GABA)) have been implicated in PG. These systems represent potential targets for psychopharmacological treatments for PG, with opioid antagonists arguably showing the most consistent benefit in RCTs. In the past year and half since this publication was prepared, there has been one additional randomized clinical trial (RCT) published along with a single case study. Our original manuscript did not describe in detail findings from case studies or open-label studies so in addition to the new RCT data and a new case report involving naltrexone, here we describe case and open-label findings. A PubMed search was conducted using terms such as “pathological gambling treatment”, “clinical trials and gambling”, and “gambling psychopharmacology.” Using these search terms, numerous results were obtained, necessitating further search modifiers. For example, using just “pathological gambling treatment” results in over 1600 hits. In order to focus in on the search modalities, we searched within the initial results for specific phrases such as “psychopharmacology, clinical trial, medication, serotonergic, dopaminergic, etc.” in addition to searching for specific medications. Results not directly related to the treatment of pathological gambling were not included. The study of pathological gambling is relatively new. As such, our search did not exclude any studies due to age of material, but with a few exceptions, the majority of the studies discussed were published later than 2000. This resulted in 24 case studies and/or RCTs not previously included in our original review article. These findings in conjunction with our prior publication provide a

  18. Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?

    PubMed Central

    Garcia-Portilla, Maria Paz; Bobes-Bascaran, Maria Teresa; Bascaran, Maria Teresa; Saiz, Pilar Alejandra; Bobes, Julio

    2014-01-01

    The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence. PMID:23145768

  19. PTSD and comorbid AUD: a review of pharmacological and alternative treatment options

    PubMed Central

    Ralevski, Elizabeth; Olivera-Figueroa, Lening A; Petrakis, Ismene

    2014-01-01

    Background Although posttraumatic stress disorder (PTSD) and alcohol use disorders (AUD) frequently co-occur there are no specific treatments for individuals diagnosed with these comorbid conditions. The main objectives of this paper are to review the literature on pharmacological options for PTSD and comorbid AUD, and to summarize promising behavioral and alternative interventions for those with these dual diagnoses. Methods We conducted a comprehensive search on PsycINFO and MEDLINE/PubMed databases using Medical Subject Headings terms in various combinations to identify articles that used pharmacotherapy for individuals with dual diagnoses of PTSD and AUD. Similar strategies were used to identify articles on behavioral and alternative treatments for AUD and PTSD. We identified and reviewed six studies that tested pharmacological treatments for patients with PTSD and comorbid AUD. Results The literature on treatment with US Food and Drug Administration approved medications for patients with dual diagnosis of PTSD and AUD is very limited and inconclusive. Promising evidence indicates that topiramate and prazosin may be effective in reducing PTSD and AUD symptoms in individuals with comorbidity. Seeking safety has had mixed efficacy in clinical trials. The efficacy of other behavioral and alternative treatments (mindfulness-based, yoga, and acupuncture) is more difficult to evaluate since the evidence comes from small, single studies without comparison groups. Conclusion There is a clear need for more systematic and rigorous study of pharmacological, behavioral, and alternative treatments for patients with dual diagnoses of PTSD and AUD. PMID:24648794

  20. Current Controversies in the Pharmacological Treatment of Chronic Obstructive Pulmonary Disease.

    PubMed

    Singh, Dave; Roche, Nicolas; Halpin, David; Agusti, Alvar; Wedzicha, Jadwiga A; Martinez, Fernando J

    2016-09-01

    Clinical phenotyping is currently used to guide pharmacological treatment decisions in chronic obstructive pulmonary disease (COPD), a personalized approach to care. Precision medicine integrates biological (endotype) and clinical (phenotype) information for a more individualized approach to pharmacotherapy, to maximize the benefit versus risk ratio. Biomarkers can be used to identify endotypes. To evolve toward precision medicine in COPD, the most appropriate biomarkers and clinical characteristics that reliably predict treatment responses need to be identified. FEV1 is a marker of COPD severity and has historically been used to guide pharmacotherapy choices. However, we now understand that the trajectory of FEV1 change, as an indicator of disease activity, is more important than a single FEV1 measurement. There is a need to develop biomarkers of disease activity to enable a more targeted and individualized approach to pharmacotherapy. Recent clinical trials testing commonly used COPD treatments have provided new information that is likely to influence pharmacological treatment decisions both at initial presentation and at follow up. In this Perspective, we consider the impact of recent clinical trials on current COPD treatment recommendations. We also focus on the movement toward precision medicine and propose how this field needs to evolve in terms of using clinical characteristics and biomarkers to identify the most appropriate patients for a given pharmacological treatment. PMID:27585383

  1. Are we taking full advantage of the growing number of pharmacological treatment options for osteoporosis?

    PubMed Central

    Jepsen, Karl J.; Schlecht, Stephen H.; Kozloff, Kenneth M.

    2014-01-01

    We are becoming increasingly aware that the manner in which our skeleton ages is not uniform within and between populations. Pharmacological treatment options with the potential to combat age-related reductions in skeletal strength continue to become available on the market, notwithstanding our current inability to fully utilize these treatments by accounting for an individual’s unique biomechanical needs. Revealing new molecular mechanisms that improve the targeted delivery of pharmaceuticals is important; however, this only addresses one part of the solution for differential age-related bone loss. To improve current treatment regimes, we must also consider specific biomechanical mechanisms that define how these molecular pathways ultimately impact whole bone fracture resistance. By improving our understanding of the relationship between molecular and biomechanical mechanisms, clinicians will be better equipped to take full advantage of the mounting pharmacological treatments available. Ultimately this will enable us to reduce fracture risk among the elderly more strategically, more effectively, and more economically. In this interest, the following review summarizes the biomechanical basis of current treatment strategies while defining how different biomechanical mechanisms lead to reduced fracture resistance. It is hoped that this may serve as a template for the identification of new targets for pharmacological treatments that will enable clinicians to personalize care so that fracture incidence may be globally reduced. PMID:24747363

  2. The meaning of pharmacological treatment for schizophrenic patients1

    PubMed Central

    Vedana, Kelly Graziani Giacchero; Miasso, Adriana Inocenti

    2014-01-01

    OBJECTIVE: to understand the meaning of medication therapy for schizophrenic patients and formulate a theoretical model about the study phenomenon. METHOD: a qualitative approach was employed, using Symbolic Interactionism as the theoretical and Grounded Theory as the methodological framework. The research was developed between 2008 and 2010 at three community mental health services in the interior of the State of São Paulo - Brazil. Thirty-six patients and thirty-six family members were selected through theoretical sampling. The data were mainly collected through open interviews and observation and simultaneously analyzed through open, axial and selective coding. RESULTS: the meaning of the pharmacotherapy is centered on the phenomenon "Living with a help that bothers", which expresses the patients' ambivalence towards the medication and determines their decision making. The insight, access, limitations for self-administration of the drugs and interactions with family members and the health team influenced the patient's medication-related behavior. CONCLUSION: the theory presented in this study provides a comprehensive, contextualized, motivational and dynamic understanding of the relation the patient experiences and indicates potentials and barriers to follow the medication treatment. PMID:25296152

  3. Physical Training as Non-Pharmacological Treatment of Neurocardiogenic Syncope

    PubMed Central

    Takahagi, Vanessa Cristina Miranda; Costa, Daniela Caetano; Crescêncio, Júlio César; Gallo, Lourenço

    2014-01-01

    Background Characterized as a sudden and temporary loss of consciousness and postural tone, with quick and spontaneous recovery, syncope is caused by an acute reduction of systemic arterial pressure and, therefore, of cerebral blood flow. Unsatisfactory results with the use of drugs allowed the nonpharmacological treatment of neurocardiogenic syncope was contemplated as the first therapeutic option. Objectives To compare, in patients with neurocardiogenic syncope, the impact of a moderate intensity aerobic physical training (AFT) and a control intervention on the positivity of head-up tilting test (HUT) and orthostatic tolerance time. Methods Were studied 21 patients with a history of recurrent neurocardiogenic syncope and HUT. The patients were randomized into: trained group (TG), n = 11, and control group (CG), n = 10. The TG was submitted to 12 weeks of AFT supervised, in cycle ergometer, and the CG to a control procedure that consisted in 15 minutes of stretching and 15 minutes of light walk. Results The TG had a positive effect to physical training, with a significant increase in peak oxygen consumption. The CG did not show any statistically significant change before and after the intervention. After the intervention period, 72.7% of the TG sample had negative results to the HUT, not having syncope in the revaluation. Conclusion The program of supervised aerobic physical training for 12 weeks was able to reduce the number of positive HUT, as it was able to increase tolerance time in orthostatic position during the HUT after the intervention period. PMID:24714795

  4. Pharmacological treatment of antipsychotic-induced dyslipidemia and hypertension.

    PubMed

    Tse, Lurdes; Procyshyn, Ric M; Fredrikson, Diane H; Boyda, Heidi N; Honer, William G; Barr, Alasdair M

    2014-05-01

    Second-generation antipsychotics (SGAs) are associated with significant comorbid metabolic abnormalities. Adjunct medications may be prescribed to treat these metabolic side effects, but the evidence supporting this practice (especially for the management of antipsychotic-associated dyslipidemia and hypertension) is limited. The purpose of this review was to evaluate the effects of adjunct medications on triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein, and blood pressure levels in participants taking SGAs for psychosis. Studies were systematically searched and evaluated. Studies were included for review if participants were taking SGAs and if lipid and/or blood pressure levels were included as outcome measures. Statins, conventional lipid-lowering agents, fluvoxamine, ramelteon, topiramate, valsartan, telmisartan, omega-3 fatty acids, metformin (including both immediate-release and extended-release formulations), and a combination of metformin-sibutramine seemed to have beneficial effects on lipid levels. Valsartan, telmisartan, and topiramate appeared to be effective for controlling increases in blood pressure. The literature on adjunct medications for the treatment of antipsychotic-associated dyslipidemia and hypertension is not exhaustive, and long-term randomized-controlled trials would offer valuable results. PMID:24169026

  5. PHARMACOLOGIC TREATMENT OF HYPERALGESIA EXPERIMENTALLY INDUCED BY NUCLEUS PULPOSUS

    PubMed Central

    de Souza Grava, André Luiz; Ferrari, Luiz Fernando; Parada, Carlos Amílcar; Defino, Helton Luiz Aparecido

    2015-01-01

    Objective: To evaluate the effect of anti-inflammatory drugs (dexamethasone, indomethacin, atenolol and indomethacin plus atenolol) and analgesic drugs (morphine) on hyperalgesia experimentally induced by the nucleus pulposus (NP) in contact with the L5 dorsal root ganglion (DRG). Methods: Thirty male Wistar rats of weights ranging from 220 to 250 g were used in the study. Hyperalgesia was induced by means of a fragment of NP removed from the sacrococcygeal region that was placed in contact with the L5 dorsal root ganglion. The 30 animals were divided into experimental groups according to the drug used. The drugs were administered for two weeks after the surgical procedure to induce hyperalgesia. Mechanical and thermal hyperalgesia was evaluated using the paw pressure test, von Frey electronic test and Hargreaves test, over a seven-week period. Results: The greatest reduction of hyperalgesia was observed in the group of animals treated with morphine, followed by dexamethasone, indomethacin and atenolol. Reductions in hyperalgesia were observed after drug administration ceased, except for the group of animals treated with morphine, in which there was an increase in hyperalgesia after discontinuation of the treatment. Conclusion: Hyperalgesia induced by NP contact with the DRG can be reduced through administration of anti-inflammatory and analgesic drugs, but a greater reduction was observed with the administration of dexamethasone. PMID:27026966

  6. Pharmacological interventions in the treatment of the acute effects of cannabis: a systematic review of literature

    PubMed Central

    2012-01-01

    Background Cannabis intoxication is related to a number of physical and mental health risks with ensuing social costs. However, little attention has been given to the investigation of possible pharmacological interactions in this condition. Objective To review the available scientific literature concerning pharmacological interventions for the treatment of the acute effects of cannabis. Methods A search was performed on the Pubmed, Lilacs, and Scielo online databases by combining the terms cannabis, intoxication, psychosis, anxiety, and treatment. The articles selected from this search had their reference lists checked for additional publications related to the topic of the review. Results The reviewed articles consisted of case reports and controlled clinical trials and are presented according to interventions targeting the physiological, psychiatric, and cognitive symptoms provoked by cannabis. The pharmacological interventions reported in these studies include: beta-blockers, antiarrhythmic agents, antagonists of CB-1 and GABA-benzodiazepine receptors, antipsychotics, and cannabidiol. Conclusion Although scarce, the evidence on pharmacological interventions for the management of cannabis intoxication suggests that propanolol and rimonabant are the most effective compounds currently available to treat the physiological and subjective effects of the drug. Further studies are necessary to establish the real effectiveness of these two medications, as well as the effectiveness of other candidate compounds to counteract the effects of cannabis intoxication, such as cannabidiol and flumazenil. PMID:22273390

  7. Patient Preference for Psychological vs. Pharmacological Treatment of Psychiatric Disorders: A Meta-Analytic Review

    PubMed Central

    McHugh, R. Kathryn; Whitton, Sarah W.; Peckham, Andrew D.; Welge, Jeffrey A.; Otto, Michael W.

    2014-01-01

    Objective Models of evidence-based practice emphasize the consideration of treatment efficacy/effectiveness, clinical expertise, and patient preference in treatment selection and implementation. However, patient preference for psychiatric treatment has been understudied. The aim of this meta-analytic review was to provide an estimate of the proportion of patients preferring psychological treatment relative to medication for psychiatric disorders. Data Sources A literature search was conducted using PubMed, PsycINFO, and the Cochrane Collaboration Library through August, 2011 for studies written in English that assessed patient preferences for the treatment of psychiatric disorders. Study Selection Studies assessing the preferred type of treatment including at least one psychological treatment and one pharmacological treatment were included. Of the 641 articles initially identified, 34 met criteria for inclusion. Data Extraction Authors extracted relevant data including the proportion of participants reporting preference for psychological and pharmacological treatment. Results Across studies, the proportion preferring psychological treatment was 0.75 (95% CI: 0.69 to 0.80), which was significantly higher than equivalent preference (i.e., higher than 0.50, p < .001). Sensitivity analyses suggested that younger patients (p < .05) and women (p < .01) were significantly more like to choose psychological treatment. A preference for psychological treatment was consistently evident in both treatment-seeking and unselected samples (ps < .05), but was somewhat stronger for the unselected samples. Conclusions Aggregation of patient preferences across diverse settings yielded a significant three-fold preference for psychological treatment relative to medication. Given the similar efficacy of these treatments for depression and anxiety, improving access to evidence-based psychological treatment is needed to connect more patients to their preferred treatment. PMID:23842011

  8. Addressing the unmet needs of patients with persistent negative symptoms of schizophrenia: emerging pharmacological treatment options

    PubMed Central

    Chue, Pierre; Lalonde, Justine K

    2014-01-01

    The negative symptoms of schizophrenia represent an impairment of normal emotional responses, thought processes and behaviors, and include blunting or flattening of affect, alogia/aprosody, avolition/apathy, anhedonia, and asociality. Negative symptoms contribute to a reduced quality of life, increased functional disability, increased burden of illness, and poorer long-term outcomes, to a greater degree than positive symptoms. Primary negative symptoms are prominent and persistent in up to 26% of patients with schizophrenia, and they are estimated to occur in up to 58% of outpatients at any given time. Negative symptoms respond less well to medications than positive symptoms, and to date treatment options for negative symptoms have been limited, with no accepted standard treatment. Modest benefits have been reported with a variety of different agents, including second-generation antipsychotics and add-on therapy with antidepressants and other pharmacological classes. Recent clinical research focusing on negative symptoms target novel biological systems, such as glutamatergic neurotransmission. Different approaches include: enhancing N-methyl-D-aspartate receptor function with agents that bind directly to the glycine ligand site or with glycine reuptake inhibitors; influencing the metabotropic glutamate receptor (mGluR2/3) with positive allosteric modulators; and stimulating nicotinic acetylcholine receptors. In conclusion, the lack of clearly efficacious pharmacological treatments for the management of negative symptoms represents a significant unmet need, especially considering the importance of these symptoms on patient outcomes. Hence, further research to identify and characterize novel pharmacological treatments for negative symptoms is greatly needed. PMID:24855363

  9. Systematic Review of Pharmacological and Behavioral Treatments for Skin Picking Disorder.

    PubMed

    Schumer, Maya C; Bartley, Christine A; Bloch, Michael H

    2016-04-01

    Skin picking disorder (SPD) is a newly recognized psychiatric disorder in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. A systematic review was conducted to assess the efficacy of pharmacological and behavioral interventions for SPD. Electronic databases were searched for randomized controlled trials (RCTs) or uncontrolled trials involving at least 10 subjects that examined the efficacy of pharmacological and behavioral interventions for SPD. We examined the improvement associated with interventions compared with inactive control conditions in RCTs and improvement over time in uncontrolled trials and within the treatment arms of RCTs. We stratified studies on the basis of intervention type. Meta-analysis included 11 studies. All interventions (including inactive control conditions) demonstrated significant improvement over the course of short-term clinical trials in SPD. Only behavioral treatments demonstrated significant benefits compared with inactive control conditions. There was no evidence from RCTs that pharmacotherapy with selective serotonin reuptake inhibitors or lamotrigine were more effective at treating SPD than placebo. Our meta-analysis suggests that subjects with SPD show significant improvement during short-term trials, regardless of the efficacy of the underlying intervention. This finding suggests that uncontrolled trials are of particularly limited utility for assessing efficacy of treatments in SPD. Future research should concentrate on developing larger placebo-controlled RCTs to examine efficacy of novel pharmacological agents. In addition, research should focus on improving accessibility of behavioral treatments with demonstrated efficacy for SPD. PMID:26872117

  10. Pharmacological treatments for fatigue associated with palliative care: executive summary of a Cochrane Collaboration systematic review

    PubMed Central

    Mochamat; Cuhls, Henning; Peuckmann‐Post, Vera; Minton, Ollie; Stone, Patrick; Radbruch, Lukas

    2016-01-01

    Abstract Background In palliative care patients, fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Further complicating issues are the multidimensionality, subjective nature and lack of a consensus definition of fatigue. The review aimed to evaluate the efficacy of pharmacological treatments for fatigue in palliative care, with a focus on patients at an advanced stage of disease, including patients with cancer and other chronic diseases. Methods We considered randomized controlled trials concerning adult palliative care with a focus on pharmacological treatment of fatigue compared with placebo, application of two drugs, usual care or a non‐pharmacological intervention. The primary outcome had to be non‐specific fatigue (or related terms such as asthenia). We searched the CENTRAL, MEDLINE, PsycINFO and EMBASE, and a selection of cancer journals up to 28 April 2014. Two review authors independently assessed trial quality and extracted the data. Results We screened 1645 publications of which 45 met the inclusion criteria. In total, we analysed data from 18 drugs and 4696 participants. There was a very high degree of statistical and clinical heterogeneity in the trials. Meta‐analysis of data was possible for modafinil, pemoline, and methylphenidate. Conclusions Due to the limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Some drugs, which may be beneficial for the treatment of fatigue associated with palliative care such as amantadine, methylphenidate, and modafinil, should be further researched. PMID:27066315

  11. Pharmacological treatment and demographic characteristics of pediatric patients with Attention Deficit Hyperactivity Disorder, Sweden.

    PubMed

    Bahmanyar, Shahram; Sundström, Anders; Kaijser, Magnus; von Knorring, Anne-Liis; Kieler, Helle

    2013-12-01

    The aim of this study was to describe the pediatric population with ADHD and their pharmacological treatment. Using the Swedish National Patient Register and the Prescribed Drug Register we identified individuals below 19 years of age who were diagnosed or medically treated for ADHD for the first time 2006-2007. The unique patient identifiers were used to link information from the two registers to describe demographic characteristics, hospital care and drug treatments. Logistic regression model estimated the association between age, sex, frequency of hospitalization, diagnosis or treatment for other mental disorders and risk of gap in the treatment. Totally the study included 7931 patients of whom 74% were males. The mean age at first diagnosis was 12 years. Some 84% were medically treated for ADHD and approximately 90% received methylphenidate as the first substance. Combination therapy was rare and the most common combination was methylphenidate and atomoxetine. More than 55% of the patients, which could be followed up for two years after start of treatment, had at least one treatment gap of six months. Older age at diagnosis, lower number of hospitalizations and comorbidity with other mental disorders increased risks of gaps in medication. Approximately one fifth of the patients recorded in the National Patient Register as diagnosed with ADHD did not receive pharmacological treatment. Medication adherence seems to be low, when measured as gaps in treatment. PMID:23953271

  12. Investigation of original multivalent iminosugars as pharmacological chaperones for the treatment of Gaucher disease.

    PubMed

    Laigre, Eugénie; Hazelard, Damien; Casas, Josefina; Serra-Vinardell, Jenny; Michelakakis, Helen; Mavridou, Irene; Aerts, Johannes M F G; Delgado, Antonio; Compain, Philippe

    2016-06-24

    Multivalent iminosugars conjugated with a morpholine moiety and/or designed as prodrugs have been prepared and evaluated as new classes of pharmacological chaperones for the treatment of Gaucher disease. This study further confirms the interest of the prodrug concept and shows that the addition of a lysosome-targeting morpholine unit into iminosugar cluster structures has no significant impact on the chaperone activity on Gaucher cells. PMID:27063390

  13. [Major depression in the child: validation of the syndrome and pharmacologic treatment].

    PubMed

    Goulet, J

    1989-02-01

    The concept of childhood depression has been the object of controversies over many years. Recent developments have permitted rapid progress in many areas of research. The author offers an update on the validity of the diagnosis of major depression in childhood and on pharmacological treatment. He then attempts to delineate the uses and limitations of this therapeutic approach. In the latter part, practical advice on the use of drugs in childhood depression is given. PMID:2647269

  14. Treating the insomniac patient - General measures and psychological and pharmacological treatment

    NASA Technical Reports Server (NTRS)

    Kales, A.; Bixler, E. O.; Kales, J. D.

    1975-01-01

    The general preliminary measures for treating insomnia include moderate physical exercise several hours before bedtime, and the relaxation of complex mental activity before bedtime. A case history concerning a woman with marital troubles is offered as evidence that insomnia may be caused by deeply rooted psychological and situational problems. Another case history illustrates how prior pharmacological treatment may complicate the process of clinically evaluating an insomniac.

  15. Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review.

    PubMed

    Perna, Giampaolo; Alciati, Alessandra; Riva, Alice; Micieli, Wilma; Caldirola, Daniela

    2016-03-01

    Many aspects of long-term pharmacological treatments for anxiety disorders (AnxDs) are still debated. We undertook an updated systematic review of long-term pharmacological studies on panic disorder (PD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). Relevant studies dating from January 1, 2012 to August 31, 2015 were identified using the PubMed database and a review of bibliographies. Of 372 records identified in the search, five studies on PD and 15 on GAD were included in the review. No studies on SAD were found. Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy. Paroxetine, escitalopram, and clonazepam can be effective for long-term treatment of PD. However, further studies are needed to draw conclusions about the long-term benzodiazepine use in PD, particularly for the possible cognitive side-effects over time. Pregabalin and quetiapine can be effective for long-term treatment of GAD, while preliminary suggestions emerged for agomelatine and vortioxetine. We did not find any evidence for determining the optimal length and/or dosage of medications to minimize the relapse risk. Few investigations have attempted to identify potential predictors of long-term treatment response. Personalized treatments for AnxDs can be implemented using predictive tools to explore those factors affecting treatment response/tolerability heterogeneity, including neurobiological functions/clinical profiles, comorbidity, biomarkers, and genetic features, and to tailor medications according to each patient's unique features. PMID:26830881

  16. Pharmacological treatment of Alzheimer's dementia: state of the art and current dilemmas.

    PubMed

    Omerovic, Muamer; Hampel, Harald; Teipel, Stefan J; Buerger, Katharina

    2008-01-01

    Alzheimer's disease (AD) is one of the most frequent disorders of the central nervous system characterised by a progressive cognitive decline. The demographic changes of our aging population lead to increased numbers of patients and a need of early diagnosis and treatment of cognitive and behavioural symptoms of AD. Drugs are available for symptomatic treatment of AD. The pharmacological treatment of behavioural disturbances experienced dynamic changes in the last years. In this paper, we present the current state and future perspectives in the treatment of AD. Furthermore, we discuss current difficulties regarding AD treatment by looking for explanations for a still unsatisfying rate of state-of-the-art treatment of AD-patients. PMID:17886162

  17. Managing insomnia: an overview of insomnia and pharmacologic treatment strategies in use and on the horizon.

    PubMed

    Schwartz, Thomas L; Goradia, Viral

    2013-10-01

    This review explores basic sleep physiology, the mechanism of action for each class of hypnotic agents, their clinical application based on pharmacodynamic and pharmacokinetic factors, and potential pharmacologic sleep-inducing mechanisms of future hypnotics. The paper challenges the reader to understand the neuroscientific basis of insomnia and use this knowledge to guide prescription of hypnotic agents. Currently indicated hypnotic agents are discussed with regard to their mechanism of drug action and clinical application. A broader discussion is developed throughout this paper regarding other non-indicated agents that may improve sleep and describing newer pharmacological treatments that may become available in the future for use in sleep disorders and their comorbid conditions. PMID:24432044

  18. Pharmacological induction of mitochondrial biogenesis as a therapeutic strategy for the treatment of type 2 diabetes.

    PubMed

    Zamora, Mònica; Pardo, Rosario; Villena, Josep A

    2015-11-01

    Defects in mitochondrial oxidative function have been associated with the onset of type 2 diabetes. Although the causal relationship between mitochondrial dysfunction and diabetes has not been fully established, numerous studies indicate that improved glucose homeostasis achieved via lifestyle interventions, such as exercise or calorie restriction, is tightly associated with increased mitochondrial biogenesis and oxidative function. Therefore, it is conceivable that potentiating mitochondrial biogenesis by pharmacological means could constitute an efficacious therapeutic strategy that would particularly benefit those diabetic patients who cannot adhere to comprehensive programs based on changes in lifestyle or that require a relatively rapid improvement in their diabetic status. In this review, we discuss several pharmacological targets and drugs that modulate mitochondrial biogenesis as well as their potential use as treatments for insulin resistance and diabetes. PMID:26212547

  19. Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV.

    PubMed

    MacBrayne, Christine E; Kiser, Jennifer J

    2016-07-15

    Roughly one-third of individuals living with the human immunodeficiency virus (HIV) are coinfected with the hepatitis C virus (HCV) due to shared routes of transmission. HIV accelerates the progression of HCV disease; thus, coinfected individuals are at high priority for HCV treatment. Several new HCV therapies, called direct-acting antiviral agents (DAAs), are available that achieve cure rates of >90% in many patient populations including individuals with HIV. The primary consideration in treating HCV in HIV-infected persons is the potential for drug interactions. We describe the clinical pharmacology and drug interaction potential of the DAAs, review the interaction data with DAAs and antiretroviral agents, and identify the knowledge gaps in the pharmacologic aspects of treating HCV in individuals with HIV coinfection. This review will focus on DAAs that have received regulatory approval in the United States and Europe and agents in late stages of clinical development. PMID:27363437

  20. Managing insomnia: an overview of insomnia and pharmacologic treatment strategies in use and on the horizon

    PubMed Central

    Schwartz, Thomas L; Goradia, Viral

    2013-01-01

    This review explores basic sleep physiology, the mechanism of action for each class of hypnotic agents, their clinical application based on pharmacodynamic and pharmacokinetic factors, and potential pharmacologic sleep-inducing mechanisms of future hypnotics. The paper challenges the reader to understand the neuroscientific basis of insomnia and use this knowledge to guide prescription of hypnotic agents. Currently indicated hypnotic agents are discussed with regard to their mechanism of drug action and clinical application. A broader discussion is developed throughout this paper regarding other non-indicated agents that may improve sleep and describing newer pharmacological treatments that may become available in the future for use in sleep disorders and their comorbid conditions. PMID:24432044

  1. Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan

    PubMed Central

    Doyle, Carolyn A.; McDougle, Christopher J.

    2012-01-01

    This review outlines pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders (ASDs) in children, adolescents, and adults. Symptom domains include repetitive and stereotyped behaviors, irritability and aggression, hyperactivity and inattention, and social impairment. Medications covered include serotonin reuptake inhibitors (SRIs), mirtazapine, antipsychotics, psychostimulants, atomoxetine, α-2 agonists, D-cycloserine, and memantine. Overall, SRIs are less efficacious and more poorly tolerated in children with ASDs than in adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in ASDs, and may be useful in the treatment of other symptoms. Psychostimulants demonstrate some benefit for the treatment of hyperactivity and inattention in individuals with ASDs, but are less efficacious and associated with more adverse effects compared with individuals with ADHD. D-cycloserine and memantine appear helpful in the treatment of social impairment, although further research is needed. PMID:23226952

  2. Clinical practices in the pharmacological treatment of comorbid psychopathology in adolescents with alcohol use disorders.

    PubMed

    Clark, Duncan B; Wood, D Scott; Cornelius, Jack R; Bukstein, Oscar G; Martin, Christopher S

    2003-12-01

    This study examined the use of psychiatric medications in 277 adolescents in treatment for alcohol use disorders. Subjects were recruited from addictions treatment sites, psychiatric programs, and juvenile justice settings. Characteristics studied included the use of and indications for specific medications, changes in clinical practices from 1991 through 2000, and continuation of psychopharmacological treatment over a 1-year followup period. Among adolescents taking psychiatric medications at baseline (n = 51), indicated DSM-IV mental disorders were typically present, use of antidepressants was most common (n = 41), benzodiazepine prescription was rare, and about one third reported continuing pharmacological treatment at one-year followup. In those with comorbid major depressive disorder and alcohol use disorders (n = 110), antidepressant medication use increased significantly from 18% to 55% over the decade studied. The treatment setting did not significantly influence antidepressant prescribing practices. The common and increasing use of psychiatric medications in this population emphasizes the urgent need for empirically based clinical guidelines. PMID:14693259

  3. Recurrent Vascular Headache: Home-Based Behavioral Treatment versus Abortive Pharmacological Treatment.

    ERIC Educational Resources Information Center

    Holroyd, Kenneth A.; And Others

    1988-01-01

    Compared the effectiveness of a home-based behavioral intervention (relaxation and thermal biofeedback training) with an abortive pharmacological intervention (with compliance training) for treating recurrent migraine and migraine/tension headaches. Both interventions yielded reductions in headache activity, psychosomatic symptoms, and daily life…

  4. Combining Pharmacological and Psychological Treatments for Binge Eating Disorder: Current Status, Limitations, and Future Directions.

    PubMed

    Grilo, Carlos M; Reas, Deborah L; Mitchell, James E

    2016-06-01

    Binge eating disorder (BED) is characterized by recurrent binge eating and marked distress about binge eating without the extreme compensatory behaviors for weight control that characterize other eating disorders. BED is prevalent, associated strongly with obesity, and is associated with heightened levels of psychological, psychiatric, and medical concerns. This article provides an overview of randomized controlled treatments for combined psychological and pharmacological treatment of BED to inform current clinical practice and future treatment research. In contrast to the prevalence and significance of BED, to date, limited research has been performed on combining psychological and pharmacological treatments for BED to enhance outcomes. Our review here found that combining certain medications with cognitive behavioral therapy (CBT) or behavioral weight loss (BWL) interventions produces superior outcomes to pharmacotherapy only but does not substantially improve outcomes achieved with CBT/BWL only. One medication (orlistat) has improved weight losses with CBT/BWL albeit minimally, and only one medication (topiramate) has enhanced reductions achieved with CBT in both binge eating and weight. Implications for future research are discussed. PMID:27086316

  5. Development of a self-treatment approach for patients with COPD and comorbidities: an ongoing learning process

    PubMed Central

    Lenferink, Anke; Buckman, Julie; Spicer, Deborah; Cafarella, Paul A.; Burt, Morton G.; Bassett, Katherine L.; van Ommeren, Clara; Anesbury, Sally; van der Valk, Paul D L P M; Frith, Peter A.; van der Palen, Job

    2014-01-01

    Background Patient-initiated action plans are an important component of COPD self-management (SM) interventions. When integrated into SM interventions, these action plans have proven to be effective in reducing exacerbation severity, hospitalisations, and costs and in improving health status in patients with COPD without severe comorbidities. Because of overlap in symptoms, a self-treatment (ST) approach that focuses solely on traditional symptoms of COPD is inadequate for patients with COPD and comorbidities. The COPE-III SM intervention combines (I) patient-initiated action plans that are tailored to the individual’s co-morbid disease(s), and (II) ongoing nurse support. In this paper we provide information regarding the integration of information from two previous COPD SM studies (COPE I and II) in the development of the current COPE-III ST approach. Materials and methods COPE-III ST materials include daily symptom diaries and action plans that take patient’s common comorbidities [chronic heart failure (CHF), anxiety, depression, ischaemic heart disease (IHD), and diabetes] into account. The comorbid diary and action plans components were developed in collaboration with multiple disease-experts. Results Previous SM studies have highlighted some essential topics that need to be considered when developing a SM or ST approach: ‘when to initiate ST’, ‘how to optimize materials and safety’, and ‘how to achieve behavioural change’. In the COPE-III study, ST is initiated after a significant change in symptoms. This is consistent with the COPE-II approach and was implemented because disease symptoms are often present even when patients are stable. We have tried to ensure patient safety by providing an easily accessible case-manager to patients throughout their involvement in the study. Furthermore, a psychologist has ensured the use of behavioural change techniques throughout the intervention. Conclusions We should continue to learn from our experiences

  6. Identification of validated questionnaires to measure adherence to pharmacological antihypertensive treatments

    PubMed Central

    Pérez-Escamilla, Beatriz; Franco-Trigo, Lucía; Moullin, Joanna C; Martínez-Martínez, Fernando; García-Corpas, José P

    2015-01-01

    Background Low adherence to pharmacological treatments is one of the factors associated with poor blood pressure control. Questionnaires are an indirect measurement method that is both economic and easy to use. However, questionnaires should meet specific criteria, to minimize error and ensure reproducibility of results. Numerous studies have been conducted to design questionnaires that quantify adherence to pharmacological antihypertensive treatments. Nevertheless, it is unknown whether questionnaires fulfil the minimum requirements of validity and reliability. The aim of this study was to compile validated questionnaires measuring adherence to pharmacological antihypertensive treatments that had at least one measure of validity and one measure of reliability. Methods A literature search was undertaken in PubMed, the Excerpta Medica Database (EMBASE), and the Latin American and Caribbean Health Sciences Literature database (Literatura Latino-Americana e do Caribe em Ciências da Saúde [LILACS]). References from included articles were hand-searched. The included papers were all that were published in English, French, Portuguese, and Spanish from the beginning of the database’s indexing until July 8, 2013, where a validation of a questionnaire (at least one demonstration of the validity and at least one of reliability) was performed to measure adherence to antihypertensive pharmacological treatments. Results A total of 234 potential papers were identified in the electronic database search; of these, 12 met the eligibility criteria. Within these 12 papers, six questionnaires were validated: the Morisky–Green–Levine; Brief Medication Questionnaire; Hill-Bone Compliance to High Blood Pressure Therapy Scale; Morisky Medication Adherence Scale; Treatment Adherence Questionnaire for Patients with Hypertension (TAQPH); and Martín–Bayarre–Grau. Questionnaire length ranged from four to 28 items. Internal consistency, assessed by Cronbach’s α, varied from 0

  7. Pharmacological telomerase inhibition can sensitize drug-resistant and drug-sensitive cells to chemotherapeutic treatment.

    PubMed

    Ward, Ryan J; Autexier, Chantal

    2005-09-01

    Effective strategies to reverse or prevent chemotherapeutic resistance are required before cancer therapies can be curative. Telomerase is the ribonucleoprotein responsible for de novo synthesis and maintenance of telomeres, and its activity is predominantly observed in cancer cells. The telomerase enzyme has been successfully inhibited or inactivated to sensitize cells to cellular stresses; however, no studies have determined yet the effect of combining a pharmacological inhibitor of telomerase catalysis and traditional chemotherapeutics for the treatment of drug-sensitive or drug-resistant cancers. Here, we describe the effect of 2-[(E)-3-naphtalen-2-yl-but-2-enoylamino]-benzoic acid (BIBR1532), a small-molecule inhibitor of telomerase catalytic activity, on drug-resistant leukemia and breast cancer cells and their parental counterparts when treated in combination with chemotherapeutics. We observed that BIBR1532-treated cells show progressive telomere shortening, decreased proliferative capacity, and sensitization to chemotherapeutic treatment. These effects are telomere length-dependent, because cells insensitive to BIBR1532 or cells released from telomerase inhibition did not demonstrate changes in growth ability or drug sensitivity. Our novel observations suggest that pharmacological telomerase inhibition in combination therapy may be a valid strategy for the treatment of both drug-sensitive and drug-resistant cancers. PMID:15939802

  8. Longitudinal clinical course following pharmacological treatment of methamphetamine psychosis which persists after long-term abstinence.

    PubMed

    Akiyama, Kazufumi

    2006-08-01

    The present article investigated clinical symptoms and their longitudinal clinical course following pharmacological treatment in 32 female incarcerated patients suffering from methamphetamine (METH) psychosis who were referred to psychiatric consultation. The length of METH-abuse periods of the patients ranged from 2 to 31 years. A total of 31 patients suffered from psychosis at abstinence after 5-31 months from the self-injection of METH. Nine of these 31 patients experienced episodes of psychotic relapse. The following symptoms were observed: auditory hallucination (29 cases), delusion of persecution (29 cases), thought broadcasting (24 cases), visual hallucination (22 cases), depressive mood (29 cases), and suicidal idea (22 cases). Patients exhibited symptoms of psychosis and depression, which persisted for more than several months despite commencement of administration of antipsychotics and antidepressants. There were significant correlations among length of periods required for improvement in total Brief Psychiatric Rating Scale (BPRS) scores, and BPRS subscale scores representing positive symptoms and depression/anxiety dimensions. Three groups of patients, according to severity of positive and depressive/anxiety symptoms, showed apparent differences in prognoses during pharmacological treatment. Average degree of extrapyramidal symptoms significantly correlated with average daily dose of antipsychotics and length-of-treatment period required for improvement in BPRS subscale scores representing positive symptom dimension. These results suggest that both psychotic and affective symptoms are involved in therapeutic response and prognosis of METH psychosis. PMID:17105910

  9. Pharmacological Treatment of Obesity in Children and Adolescents: Present and Future

    PubMed Central

    Iughetti, Lorenzo; China, Mariachiara; Berri, Rossella; Predieri, Barbara

    2011-01-01

    The prevalence of overweight and obesity is increasing in children and adolescents worldwide raising the question on the approach to this condition because of the potential morbidity, mortality, and economic tolls. Dietetic and behavioral treatments alone have only limited success; consequently, discussion on strategies for treating childhood and adolescent obesity has been promoted. Considering that our knowledge on the physiological systems regulating food intake and body weight is considerably increased, many studies have underlined the scientific and clinical relevance of potential treatments based on management of peripheral or central neuropeptides signals by drugs. In this paper, we analyze the data on the currently approved obesity pharmacological treatment suggesting the new potential drugs. PMID:21197151

  10. Novel pharmacologic treatment in acute binge eating disorder - role of lisdexamfetamine.

    PubMed

    Guerdjikova, Anna I; Mori, Nicole; Casuto, Leah S; McElroy, Susan L

    2016-01-01

    Binge eating disorder (BED) is the most common eating disorder and an important public health problem. It is characterized by recurrent episodes of excessive food consumption accompanied by a sense of loss of control over the binge eating behavior without the inappropriate compensatory weight loss behaviors of bulimia nervosa. BED affects both sexes and all age groups and is associated with medical and psychiatric comorbidities. Until recently, self-help and psychotherapy were the primary treatment options for patients with BED. In early 2015, lisdexamfetamine dimesylate, a prodrug stimulant marketed for attention deficit hyperactive disorder, was the first pharmacologic agent to be approved by the US Food and Drug Administration for the treatment of moderate or severe BED in adults. This article summarizes BED clinical presentation, and discusses the pharmacokinetic profile, efficacy, and safety of lisdexamfetamine dimesylate in the treatment of BED in adults. PMID:27143885

  11. Novel pharmacologic treatment in acute binge eating disorder – role of lisdexamfetamine

    PubMed Central

    Guerdjikova, Anna I; Mori, Nicole; Casuto, Leah S; McElroy, Susan L

    2016-01-01

    Binge eating disorder (BED) is the most common eating disorder and an important public health problem. It is characterized by recurrent episodes of excessive food consumption accompanied by a sense of loss of control over the binge eating behavior without the inappropriate compensatory weight loss behaviors of bulimia nervosa. BED affects both sexes and all age groups and is associated with medical and psychiatric comorbidities. Until recently, self-help and psychotherapy were the primary treatment options for patients with BED. In early 2015, lisdexamfetamine dimesylate, a prodrug stimulant marketed for attention deficit hyperactive disorder, was the first pharmacologic agent to be approved by the US Food and Drug Administration for the treatment of moderate or severe BED in adults. This article summarizes BED clinical presentation, and discusses the pharmacokinetic profile, efficacy, and safety of lisdexamfetamine dimesylate in the treatment of BED in adults. PMID:27143885

  12. Pharmacological and psychosomatic treatments for an elderly patient with severe nausea and vomiting in reaction to postoperative stress.

    PubMed

    Otera, Masako; Machida, Takatsugu; Machida, Tomomi; Abe, Mai; Ichie, Masayoshi; Fukudo, Shin

    2015-10-01

    Here we present a case of successful treatment employing a mixed approach including pharmacological and psychosomatic treatments for a 72-year-old woman who experienced severe nausea and vomiting in reaction to postoperative stress from gastric cancer surgery. This case demonstrates that appropriate provision of psychosomatic treatments, including a psychotherapeutic session and autogenic training, enhances the efficacy of pharmacotherapy. PMID:26259848

  13. Relaxin for the Treatment of Acute Decompensated Heart Failure: Pharmacology, Mechanisms of Action, and Clinical Evidence.

    PubMed

    Ng, Tien M H; Goland, Sorel; Elkayam, Uri

    2016-01-01

    Acute heart failure remains a major cause of morbidity, and its treatment requires an increasing investment of the health care system. Whereas success in treating chronic heart failure has been achieved over the last decades, several pharmacological approaches for acute heart failure have been introduced but have failed to demonstrate any clinical benefit. Serelaxin is a recombinant human relaxin-2 vasoactive peptide that causes systemic and renal vasodilation. Data suggest that the clinical benefits may be attributable to a potential combination of multiple actions of serelaxin, including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via neurohormonal, anti-inflammatory, antiremodeling, antifibrotic, anti-ischemic, and proangiogenic effects. Recently, a number of clinical trials have demonstrated that serelaxin infusion over 48 hours improved dyspnea with more rapid relief of congestion during the first days after admission for heart failure. In addition, administration of serelaxin diminished cardiac, renal, and hepatic damage, which were associated with improved long-term mortality. Available data support substantial clinical benefits and significant promise for serelaxin as a treatment option for patients with acute heart failure. This review focuses on the pharmacology and mechanisms of action of serelaxin and provides a detailed discussion of the clinical evidence for this novel therapy in acute heart failure. PMID:26331289

  14. Diagnosis of dementia and treatment of Alzheimer's disease. Pharmacologic management of disease progression and cognitive impairment.

    PubMed Central

    van Reekum, R.; Simard, M.; Farcnik, K.

    1999-01-01

    OBJECTIVE: To highlight the importance of family physicians in the management of Alzheimer's disease (AD) and related dementias. To provide an update on the diagnostic workup of people with suspected dementia and on the pharmacologic management of cognitive impairment and disease progression in AD. QUALITY OF EVIDENCE: MEDLINE and Psychological Abstracts were searched using the terms "cognitive enhancers" or a specific drug name and "dementia (exp)." Evidence is generally limited but promising. Methodologic flaws in existing research likely to affect clinicians are briefly reviewed. MAIN MESSAGE: Increasing evidence suggests that early intervention can delay the progression of AD and improve the symptoms and function of those affected. Available treatments have modest but important effects on the outcome of patients with AD; some patients respond dramatically. Most currently available treatments are relatively safe in carefully selected cases. CONCLUSIONS: The diagnostic workup of most cases of dementia can at least be initiated in family physicians' offices. Beginning the workup is important because, for treating AD, the earlier you start, the better. Donepezil, vitamin E, and, in the near future, propentofylline are the main pharmacologic choices for improving cognition and slowing disease progression. PMID:10216793

  15. Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment

    PubMed Central

    Gao, Li; Hao, Jian; Niu, Yang-Yang; Tian, Miao; Yang, Xue; Zhu, Cui-Hong; Ding, Xiu-Li; Liu, Xiao-Hui; Zhang, Hao-Ran; Liu, Chang; Qin, Xue-Mei; Wu, Xiong-Zhi

    2016-01-01

    Abstract Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear. In this study, the Kaplan–Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM. CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245–0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma. A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data. PMID:27583849

  16. Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment.

    PubMed

    Gao, Li; Hao, Jian; Niu, Yang-Yang; Tian, Miao; Yang, Xue; Zhu, Cui-Hong; Ding, Xiu-Li; Liu, Xiao-Hui; Zhang, Hao-Ran; Liu, Chang; Qin, Xue-Mei; Wu, Xiong-Zhi

    2016-08-01

    Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear.In this study, the Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM.CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245-0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma.A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data. PMID:27583849

  17. ITI-007 in the treatment of schizophrenia: from novel pharmacology to clinical outcomes.

    PubMed

    Davis, Robert E; Correll, Christoph U

    2016-06-01

    ITI-007 is an investigational drug being developed for schizophrenia and other neuropsychiatric/neurodegenerative diseases. ITI-007 has a unique pharmacological profile, combining potent 5-HT2a receptor antagonism with cell-type-specific dopamine and glutamate receptor modulation, plus serotonin reuptake inhibition. At dopamine-D2 receptors, ITI-007 acts as a post-synaptic antagonist and pre-synaptic partial agonist. Additionally, ITI-007 stimulates phosphorylation of glutamatergic NMDA-NR2B receptors, downstream of dopamine-D1 receptor intracellular signaling. Based on a large, placebo and risperidone controlled, Phase-II trial, ITI-007 60 mg was shown to be effective in reducing symptoms in patients with acutely exacerbated schizophrenia. The antipsychotic efficacy of ITI-007 60 mg in this patient population was confirmed in a recently completed Phase III study. ITI-007 was associated with minimal safety risk compared to risperidone (Phase II study) or placebo (both studies) for neuromotor disturbances, prolactin changes, weight gain and metabolic abnormalities. A second 6-week, placebo and risperidone-controlled Phase-III trial in acutely exacerbated schizophrenia is ongoing. PMID:27042868

  18. Pharmacological treatment of comorbid PTSD and substance use disorder: recent progress.

    PubMed

    Sofuoglu, Mehmet; Rosenheck, Robert; Petrakis, Ismene

    2014-02-01

    Previous research has identified a strong association between posttraumatic stress disorder (PTSD) and substance use disorder (SUD), necessitating the development of treatments that address both conditions. Some pharmacotherapies are effective for the treatment of PTSD and SUD alone, however; no medications have been proven to be effective for the combination of these conditions. We review the recent advances in pharmacological treatment of comorbid PTSD and SUD. A randomized clinical trial of sertraline, a serotonin reuptake inhibitor (SSRI), did not show overall efficacy for comorbid PTSD and alcohol dependence (AD), although it may have efficacy among light drinkers. Another clinical trial demonstrated the efficacy of both disulfiram and naltrexone for the treatment of AD in individuals with PTSD. A more recent clinical trial suggested that norepinephrine uptake inhibitors may also have efficacy for the treatment of comorbid PTSD and AD. In animal and preliminary human studies, brain norepinephrine and glutamate/GABA have emerged as potential treatment targets for comorbid PTSD and SUD. Noradrenergic medications that are promising for comorbid PTSD and SUD include prazosin, guanfacine, and atomoxetine. Promising glutamate/GABA medications include topiramate, memantine, acamprosate, N-acetylcysteine (NAC), and ketamine. The safety and efficacy of these medications for the treatment of PTSD and SUD need to be tested in controlled clinical trials. PMID:24035645

  19. Pharmacological and psychosocial treatments for adolescents with ADHD: an updated systematic review of the literature.

    PubMed

    Sibley, Margaret H; Kuriyan, Aparajita B; Evans, Steven W; Waxmonsky, James G; Smith, Bradley H

    2014-04-01

    Smith, Waschbusch, Willoughby, and Evans (2000) reviewed a small treatment literature on ADHD in adolescents and concluded that methylphenidate stimulant medication was a well-established treatment and behavior therapy (BT) demonstrated preliminary efficacy. This review extends and updates the findings of the prior one based on the previous 15years of research. Studies published since 1999 were identified and coded using standard criteria and effect sizes were calculated where appropriate. Highlights of the last 15years of research include an expansion of pharmacological treatment options and developmentally appropriate psychosocial treatment packages for adolescents with ADHD. Additionally, nonstimulant medications (e.g., atomoxetine) are now approved for the treatment of ADHD in adolescence. The review concludes that medication and BT produce a similar range of therapeutic effects on the symptoms of adolescents with ADHD. However, results suggest that BT may produce greater overall benefits on measures of impairment. There was no evidence that cognitive enhancement trainings, such as working memory training or neurofeedback improved the functioning of adolescents with ADHD. Whether to use medication, BT, or their combination to treat an adolescent with ADHD is complicated and we provide evidence-informed guidelines for treatment selection. The reviewed evidence does not support current American Academy of Pediatrics and American Academy of Child and Adolescent Psychiatry professional guidelines, which state that stimulant medication is the preferred treatment for adolescents with ADHD. Recommendations for assessment, practice guidelines, and future research are discussed. PMID:24632046

  20. Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

    PubMed Central

    Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C.

    2015-01-01

    Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

  1. The pathophysiological and pharmacological basis of current drug treatment of migraine headache.

    PubMed

    Reddy, Doodipala Samba

    2013-05-01

    Migraine is a common neurological syndrome that affects approximately 10-20% of the population. The pathophysiology of migraine is unclear. 5-hydroxytriptamine is a key mediator in the pathogenesis of migraine and thus 5-HT1-receptor agonists are the principal drugs for acute migraine therapy. There are three classes of drugs for migraine: over-the-counter analgesics and nonsteroidal anti-inflammatory drugs for acute mild migraine, specific prescription drugs (triptans and ergot alkaloids) for acute severe migraine and pharmacological agents for prophylaxis of migraine. Sumatriptan, naratriptan and others, referred to as 'triptans', are the mainstay for acute treatment of migraine. Ergot alkaloids (ergotamine, dihydroergotamine) are used in patients with frequent, moderate migraine, but are less effective than triptans. There are several agents for prevention of migraine occurrence in patients with frequent or severe disabling migraine attacks. New drugs with improved efficacy and reduced side effects are needed for effective treatment and prevention of migraine. PMID:23656340

  2. Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes.

    PubMed

    Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C

    2015-01-01

    Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

  3. Incorporating Stage-Specific Drug Action into Pharmacological Modeling of Antimalarial Drug Treatment

    PubMed Central

    2016-01-01

    Pharmacological modeling of antiparasitic treatment based on a drug's pharmacokinetic and pharmacodynamic properties plays an increasingly important role in identifying optimal drug dosing regimens and predicting their potential impact on control and elimination programs. Conventional modeling of treatment relies on methods that do not distinguish between parasites at different developmental stages. This is problematic for malaria parasites, as their sensitivity to drugs varies substantially during their 48-h developmental cycle. We investigated four drug types (short or long half-lives with or without stage-specific killing) to quantify the accuracy of the standard methodology. The treatment dynamics of three drug types were well characterized with standard modeling. The exception were short-half-life drugs with stage-specific killing (i.e., artemisinins) because, depending on time of treatment, parasites might be in highly drug-sensitive stages or in much less sensitive stages. We describe how to bring such drugs into pharmacological modeling by including additional variation into the drug's maximal killing rate. Finally, we show that artemisinin kill rates may have been substantially overestimated in previous modeling studies because (i) the parasite reduction ratio (PRR) (generally estimated to be 104) is based on observed changes in circulating parasite numbers, which generally overestimate the “true” PRR, which should include both circulating and sequestered parasites, and (ii) the third dose of artemisinin at 48 h targets exactly those stages initially hit at time zero, so it is incorrect to extrapolate the PRR measured over 48 h to predict the impact of doses at 48 h and later. PMID:26902760

  4. Incorporating Stage-Specific Drug Action into Pharmacological Modeling of Antimalarial Drug Treatment.

    PubMed

    Hodel, Eva Maria; Kay, Katherine; Hastings, Ian M

    2016-05-01

    Pharmacological modeling of antiparasitic treatment based on a drug's pharmacokinetic and pharmacodynamic properties plays an increasingly important role in identifying optimal drug dosing regimens and predicting their potential impact on control and elimination programs. Conventional modeling of treatment relies on methods that do not distinguish between parasites at different developmental stages. This is problematic for malaria parasites, as their sensitivity to drugs varies substantially during their 48-h developmental cycle. We investigated four drug types (short or long half-lives with or without stage-specific killing) to quantify the accuracy of the standard methodology. The treatment dynamics of three drug types were well characterized with standard modeling. The exception were short-half-life drugs with stage-specific killing (i.e., artemisinins) because, depending on time of treatment, parasites might be in highly drug-sensitive stages or in much less sensitive stages. We describe how to bring such drugs into pharmacological modeling by including additional variation into the drug's maximal killing rate. Finally, we show that artemisinin kill rates may have been substantially overestimated in previous modeling studies because (i) the parasite reduction ratio (PRR) (generally estimated to be 10(4)) is based on observed changes in circulating parasite numbers, which generally overestimate the "true" PRR, which should include both circulating and sequestered parasites, and (ii) the third dose of artemisinin at 48 h targets exactly those stages initially hit at time zero, so it is incorrect to extrapolate the PRR measured over 48 h to predict the impact of doses at 48 h and later. PMID:26902760

  5. Pharmacologic vitreolysis.

    PubMed

    Rhéaume, Marc-André; Vavvas, Demetrios

    2010-01-01

    It is now well recognized that vitreous plays an important role in the pathogenesis of various retinal disorders. In many instances it can be addressed with pars plana vitrectomy, although this approach, like any surgery, has its limitations. The search for alternatives or adjunct to surgery has led to the development of pharmacologic vitreolysis. The use of intravitreal agents to alter the vitreous in order to reduce or eliminate its role in disease seems promising. The purpose of this article is to summarize the present knowledge on pharmacologic vitreolysis. A review of the different agents used and of ongoing trials will be presented. Also, current understanding of vitreous structure and its interaction with the retina will be discussed. PMID:21091015

  6. Systems Pharmacology Dissection of the Integrated Treatment for Cardiovascular and Gastrointestinal Disorders by Traditional Chinese Medicine

    PubMed Central

    Zhang, Wenjuan; Tao, Qin; Guo, Zihu; Fu, Yingxue; Chen, Xuetong; Shar, Piar Ali; Shahen, Mohamed; Zhu, Jinglin; Xue, Jun; Bai, Yaofei; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Wang, Yonghua

    2016-01-01

    Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases. PMID:27597117

  7. Methamphetamine: An Update on Epidemiology, Pharmacology, Clinical Phenomenology, and Treatment Literature

    PubMed Central

    Courtney, Kelly E.; Ray, Lara A.

    2014-01-01

    Background Despite initial reports of a decline in use in the early 2000s, methamphetamine remains a significant public health concern with known neurotoxic and neurocognitive effects to the user. The goal of this review is to update the literature on methamphetamine use and addiction since its assent to peak popularity in 1990s. Methods Specifically, we first review recent epidemiological reports with a focus on methamphetamine accessibility, changes in use and disorder prevalence rates over time, and accurate estimates of the associated burden of care to the individual and society. Second, we review methamphetamine pharmacology literature with emphasis on the structural and functional neurotoxic effects associated with repeated use of the drug. Third, we briefly outline the findings on methamphetamine-related neurocognitive deficits as assessed via behavioral and neuroimaging paradigms. Lastly, we review the clinical presentation of methamphetamine addiction and the evidence supporting the available psychosocial and pharmacological treatments within the context of an addiction biology framework. Conclusion Taken together, this review provides a broad-based update of the available literature covering methamphetamine research over the past two decades and concludes with recommendations for future research. PMID:25176528

  8. Systems Pharmacology Dissection of the Integrated Treatment for Cardiovascular and Gastrointestinal Disorders by Traditional Chinese Medicine.

    PubMed

    Zhang, Wenjuan; Tao, Qin; Guo, Zihu; Fu, Yingxue; Chen, Xuetong; Shar, Piar Ali; Shahen, Mohamed; Zhu, Jinglin; Xue, Jun; Bai, Yaofei; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Wang, Yonghua

    2016-01-01

    Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases. PMID:27597117

  9. Pain in the cancer patient: different pain characteristics CHANGE pharmacological treatment requirements.

    PubMed

    Müller-Schwefe, Gerhard; Ahlbeck, Karsten; Aldington, Dominic; Alon, Eli; Coaccioli, Stefano; Coluzzi, Flaminia; Huygen, Frank; Jaksch, Wolfgang; Kalso, Eija; Kocot-Kępska, Magdalena; Kress, Hans-Georg; Mangas, Ana Cristina; Ferri, Cesar Margarit; Morlion, Bart; Nicolaou, Andrew; Hernández, Concepción Pérez; Pergolizzi, Joseph; Schäfer, Michael; Sichère, Patrick

    2014-09-01

    Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients' reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient's rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms - rather than being simply based on pain intensity as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level. PMID:24841174

  10. Review of Clinical Pharmacology of Aloe vera L. in the Treatment of Psoriasis.

    PubMed

    Miroddi, Marco; Navarra, Michele; Calapai, Fabrizio; Mancari, Ferdinando; Giofrè, Salvatore Vincenzo; Gangemi, Sebastiano; Calapai, Gioacchino

    2015-05-01

    Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune-mediated chronic inflammatory disease, involving mainly the skin, affects about the 2-3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions. PMID:25756474

  11. Predictors of adherence to pharmacological and behavioral treatment in a cessation trial among smokers in Aleppo, Syria

    PubMed Central

    Ben Taleb, Ziyad; Ward, Kenneth D; Asfar, Taghrid; Bahelah, Raed; Maziak, Wasim

    2015-01-01

    Introduction The development of evidence-based smoking cessation programs is in its infancy in developing countries, which continue to bear the main brunt of the tobacco epidemic. Adherence to treatment recommendations is an important determinant of the success of smoking cessation programs, but little is known about factors influencing adherence to either pharmacological or behavioral treatment in developing countries settings. Our study represents the first attempt to examine the predictors of adherence to cessation treatment in a low-income developing country. Methods Predictors of adherence to pharmacological and behavioral treatment were identified by analyzing data from a multi-site, two-group, parallel-arm, double-blind, randomized, placebo-controlled smoking cessation trial in primary care clinics in Aleppo, Syria. Participants received 3 in-person behavioral counseling sessions plus 5 brief follow-up phone counseling sessions, and were randomized to either 6 weeks of nicotine or placebo patch. Results Of the 269 participants, 68% adhered to pharmacological treatment, while 70% adhered to behavioral counseling. In logistic regression modeling, lower adherence to pharmacological and behavioral treatment was associated with higher daily smoking at baseline, greater withdrawal symptoms, and perception of receiving placebo instead of active nicotine patch. Women showed lower adherence than men to behavioral treatment, while being assigned to placebo condition and baseline waterpipe use were associated with lower adherence to pharmacological treatment. Conclusion Adherence to cessation treatment for cigarette smokers in low-income countries such as Syria may benefit from integrated cessation components that provide intensive treatment for subjects with higher nicotine dependence, and address concurrent waterpipe use at all stages. PMID:26077603

  12. Comparative Cost Analysis of Sequential, Adaptive, Behavioral, Pharmacological, and Combined Treatments for Childhood ADHD.

    PubMed

    Page, Timothy F; Pelham, William E; Fabiano, Gregory A; Greiner, Andrew R; Gnagy, Elizabeth M; Hart, Katie C; Coxe, Stefany; Waxmonsky, James G; Foster, E Michael; Pelham, William E

    2016-01-01

    We conducted a cost analysis of the behavioral, pharmacological, and combined interventions employed in a sequential, multiple assignment, randomized, and adaptive trial investigating the sequencing and enhancement of treatment for children with attention deficit hyperactivity disorder (ADHD; Pelham et al., 201X; N = 146, 76% male, 80% Caucasian). The quantity of resources expended on each child's treatment was determined from records that listed the type, date, location, persons present, and duration of all services provided. The inputs considered were the amount of physician time, clinician time, paraprofessional time, teacher time, parent time, medication, and gasoline. Quantities of these inputs were converted into costs in 2013 USD using national wage estimates from the Bureau of Labor Statistics, the prices of 30-day supplies of prescription drugs from the national Express Scripts service, and mean fuel prices from the Energy Information Administration. Beginning treatment with a low-dose/intensity regimen of behavior modification (large-group parent training) was less costly for a school year of treatment ($961) than beginning treatment with a low dose of stimulant medication ($1,669), regardless of whether the initial treatment was intensified with a higher "dose" or if the other modality was added. Outcome data from the parent study (Pelham et al., 201X) found equivalent or superior outcomes for treatments beginning with low-intensity behavior modification compared to intervention beginning with medication. Combined with the present analyses, these findings suggest that initiating treatment with behavior modification rather than medication is the more cost-effective option for children with ADHD. PMID:26808137

  13. Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic treatment of hypertensive disorders in pregnancy

    PubMed Central

    Rey, E; LeLorier, J; Burgess, E; Lange, I R; Leduc, L

    1997-01-01

    OBJECTIVE: To provide Canadian physicians with evidence-based guidelines for the pharmacologic treatment of hypertensive disorders in pregnancy. OPTIONS: No medication, or treatment with antihypertensive or anticonvulsant drugs. OUTCOMES: Prevention of maternal complications, and prevention of perinatal complications and death. EVIDENCE: Pertinent articles published from 1962 to September 1996 retrieved from the Pregnancy and Childbirth Module of the Cochrane Database of Systematic Reviews and from MEDLINE; additional articles retrieved through a manual search of bibliographies; and expert opinion. Recommendations were graded according to levels of evidence. VALUES: Maternal and fetal well-being were equally valued, with the belief that treatment side effects should be minimized. BENEFITS, HARMS AND COSTS: Reduction in the rate of adverse perinatal outcomes, including death. Potential side effects of antihypertensive drugs include placental hypoperfusion, intrauterine growth retardation and long-term effects on the infant. RECOMMENDATIONS: A systolic blood pressure greater than 169 mm Hg or a diastolic pressure greater than 109 mm Hg in a pregnant woman should be considered an emergency and pharmacologic treatment with hydralazine, labetalol or nifedipine started. Otherwise, the thresholds at which to start antihypertensive treatment are a systolic pressure of 140 mm Hg or a diastolic pressure of 90 mm Hg in women with gestational hypertension without proteinuria or pre-existing hypertension before 28 weeks' gestation, those with gestational hypertension and proteinuria or symptoms at any time during the pregnancy, those with pre-existing hypertension and underlying conditions or target-organ damage, and those with pre-existing hypertension and superimposed gestational hypertension. The thresholds in other circumstances are a systolic pressure of 150 mm Hg or a diastolic pressure of 95 mm Hg. For nonsevere hypertension, methyldopa is the first-line drug; labetalol

  14. Physical exercise as non-pharmacological treatment of chronic pain: Why and when

    PubMed Central

    Ambrose, Kirsten R.; Golightly, Yvonne M.

    2015-01-01

    Chronic pain broadly encompasses both objectively defined conditions and idiopathic conditions that lack physical findings. Despite variance in origin or pathogenesis, these conditions are similarly characterized by chronic pain, poor physical function, mobility limitations, depression, anxiety and sleep disturbance and are treated alone or in combination by pharmacologic and nonpharmacologic approaches, such as physical activity (aerobic conditioning, muscle strengthening, flexibility training and movement therapies). Physical activity improves general health, disease risk and progression of chronic illnesses such as cardiovascular disease, type-2 diabetes and obesity. When applied to chronic pain conditions within appropriate parameters (frequency, duration, intensity), physical activity significantly improves pain and related symptoms. For chronic pain, strict guidelines for physical activity are lacking, but frequent movement is preferable to sedentary behavior. This gives considerable freedom in prescribing physical activity treatments, which are most successful when tailored individually, progressed slowly and account for physical limitations, psychosocial needs and available resources. PMID:26267006

  15. [Clinical aspects of pharmacological treatment of diabetic neuropathy - cooperation with neurologists and diabetologists].

    PubMed

    Janíčková Žďárská, Denisa; Kvapil, Milan

    2016-03-01

    The development and progression of symptomatic diabetic neuropathy (SDN) is linked to hyperglycemia. The effort to improve compensation of diabetes mellitus during therapy is therefore very important. This is where the cooperation between the diabetologist and neurologist within therapy plays an important role. The pharmaco-logical therapy of symptomatic sensitive peripheral diabetic neuropathy is difficult and with a less than satisfactory effect. A variety of active substances is used in symptomatic therapy, primarily designed for intervention in other pathological conditions. The recommended guidelines include antidepressants, anticonvulsants, opiates and their derivatives. However this therapy brings with it a relatively high incidence of adverse effects which detract from patients adherence to treatment. Very good results are reached by the therapy with thioctacid. PMID:27180665

  16. Pharmacological targeting of the serotonergic system for the treatment of obesity

    PubMed Central

    Garfield, Alastair S; Heisler, Lora K

    2009-01-01

    The attenuation of food intake as induced by an increase in serotonergic (5-hydroxytryptamine, 5-HT) efficacy has been a target of antiobesity pharmacotherapies. However, the induction of tolerance and/or side-effects limited the clinical utility of the earliest serotonin-related medications. With the global prevalence of obesity rising, there has been renewed interest in the manipulation of the serotonergic system as a point of pharmacological intervention. The serotonin2C receptor (5-HT2CR), serotonin1B (rodent)/serotonin1Dβ (human) receptor (5-HT1B/1DβR) and serotonin6 receptor (5-HT6R) represent the most promising serotonin receptor therapeutic targets. Canonical serotonin receptor compounds have given way to a myriad of novel receptor-selective ligands, many of which have observable anorectic effects. Here we review serotonergic compounds reducing ingestive behaviour and discuss their clinical potential for the treatment of obesity. PMID:19029184

  17. The influence of clinical and pharmacological factors on enuresis treatment with imipramine.

    PubMed Central

    Fernández de Gatta, M M; Galindo, P; Rey, F; Gutierrez, J; Tamayo, M; García, M J; Domínguez-Gil, A

    1990-01-01

    1. The aim of this study has been to evaluate the response to imipramine treatment in enuretic children through the use of a series of clinical and pharmacological variables and by applying a multivariate (principal components) analysis technique. 2. The study was carried out on 146 children whose ages ranged from 5 to 14 years, and who received variable doses of imipramine (12.5 to 100 mg day-1). 3. The quantitative variables analyzed were: drug dosage, serum levels of imipramine and its metabolite desipramine, the relationship between them both, the duration of treatment, age and weight. 4. The qualitative variables were: compliance, presence of side-effects, enuretic and/or psychiatric antecedents, intelligence quotient (I.Q.), the existence (or absence) of related pathologies, sex, and the type of enuresis. 5. The response to treatment was quantified by means of the percentage of decrease in frequency of enuresis as compared with the initial frequency. 6. The results obtained show that the variables which are most associated with the reduction of enuresis are, in decreasing order: the dosage of imipramine administered, the duration of treatment, compliance and the level/dose ratio for the sum of the drug and metabolite levels. PMID:2271368

  18. The influence of clinical and pharmacological factors on enuresis treatment with imipramine.

    PubMed

    Fernández de Gatta, M M; Galindo, P; Rey, F; Gutierrez, J; Tamayo, M; García, M J; Domínguez-Gil, A

    1990-11-01

    1. The aim of this study has been to evaluate the response to imipramine treatment in enuretic children through the use of a series of clinical and pharmacological variables and by applying a multivariate (principal components) analysis technique. 2. The study was carried out on 146 children whose ages ranged from 5 to 14 years, and who received variable doses of imipramine (12.5 to 100 mg day-1). 3. The quantitative variables analyzed were: drug dosage, serum levels of imipramine and its metabolite desipramine, the relationship between them both, the duration of treatment, age and weight. 4. The qualitative variables were: compliance, presence of side-effects, enuretic and/or psychiatric antecedents, intelligence quotient (I.Q.), the existence (or absence) of related pathologies, sex, and the type of enuresis. 5. The response to treatment was quantified by means of the percentage of decrease in frequency of enuresis as compared with the initial frequency. 6. The results obtained show that the variables which are most associated with the reduction of enuresis are, in decreasing order: the dosage of imipramine administered, the duration of treatment, compliance and the level/dose ratio for the sum of the drug and metabolite levels. PMID:2271368

  19. Ulipristal acetate: a novel pharmacological approach for the treatment of uterine fibroids

    PubMed Central

    Biglia, Nicoletta; Carinelli, Silvestro; Maiorana, Antonio; D’Alonzo, Marta; Lo Monte, Giuseppe; Marci, Roberto

    2014-01-01

    Uterine fibroids are the most common benign tumors of the female genital tract. The management of symptomatic fibroids has traditionally been surgical; however, alternative pharmacological approaches have been proposed to control symptoms. To date, gonadotropin-releasing hormone analogs are the only available drugs for the preoperative treatment of fibroids. However, the US Food and Drug Administration recently authorized ulipristal acetate (UPA), an oral selective progesterone-receptor modulator, for the same indication. UPA is a new, effective, and well-tolerated option for the preoperative treatment of moderate and severe symptoms of uterine fibroids in women of reproductive age. According to clinical data, UPA shows several advantages: it is faster than leuprolide in reducing the fibroid-associated bleeding, it significantly improves hemoglobin and hematocrit levels in anemic patients, and it grants a significant reduction in the size of fibroids, which lasts for at least 6 months after the end of the treatment. Furthermore, UPA displays a better tolerability profile when compared to leuprolide; in fact, it keeps estradiol levels at mid follicular phase range, thereby reducing the incidence of hot flushes and exerting no impact on bone turnover. On the grounds of this evidence, the administration of 5 mg/day ulipristal acetate for 3 months is suggested for different patient categories and allows for planning a treatment strategy tailored to meet an individual patient’s needs. PMID:24591818

  20. Patient-reported outcomes in post-traumatic stress disorder Part II: Focus on pharmacological treatment

    PubMed Central

    Kapfhammer, Hans-Peter

    2014-01-01

    Post-traumatic stress disorder (PTSD) may be associated with long-lasting psychological suffering, distressing psychosocial disability, markedly reduced health-related quality of life, and increased morbidity and mortality in a subgroup of individuals in the aftermath of serious traumatic events. Both etiopathogenesis and treatment modalities of PTSD are best conceptualized within a biopsychosotial model. Pharmacotherapy may lay claim to a major role in the multimodal treatment approaches. Here we outline two different pharmacotherapeutic trends that aim to modify the encoding, consolidation, and rehearsal of traumatic memory in order to reduce the risk of PTSD immediately after trauma exposure on the one hand, and that endeavor to treat the clinical state of PTSD on the other. The theoretical rationales of both pharmacological strategies are the complex neurobiological underpinnings that characterize traumatic memory organization and clinical PTSD. Meanwhile, promising data from randomized controlled trials have been obtained for both approaches. Empirical evidence may inform clinicians in their clinical efforts for this special group of patients. The efficacy of several classes of drugs that have been investigated within a context of research should be evaluated critically and still have to stand the test of effectiveness in daily clinical practice. From a patient perspective, empirical results may serve as a psychoeducative guideline to what pharmacotherapeutic approaches may realistically achieve, what their risks and benefits are, and what their limits are in contributing to reducing the often major chronic suffering caused by serious traumatic events. Ethical issues have to be considered, particularly in the context of pharmacological strategies projected to prevent PTSD in the aftermath of traumatic exposure. PMID:25152660

  1. Overview of experimental and conventional pharmacological approaches in the treatment of sleep and wake disorders.

    PubMed

    Renger, John J

    2008-01-01

    The fundamental purpose of sleep remains one of the most compelling questions yet to be answered in the area of neuroscience, if not all of biology. A pervasive behavior among members of the animal kingdom, the functional necessity of engaging regularly in sleep is best demonstrated by showing that failing to do so leads to a broad repertoire of pathological outcomes including cognitive, immunological, hormonal, and metabolic outcomes, among others. Indeed, an absolute requirement for sleep has been shown in studies that have demonstrated that continuous total deprivation of sleep for as short a period as 15 days is generally lethal in some species. The most common clinical sleep disorder, insomnia, is both a principal disease (primary insomnia) as well as a co-morbidity of a large number of other ostensibly unrelated diseases including chronic pain, attention deficit hyperactivity disorder, and depression. From a treatment perspective, restoring normal healthy sleep delivers subsequent benefits in waking cognitive function and mood with the potential for beneficial therapeutic impact on daily functioning across multiple diseases for which restorative healthy sleep is compromised. Our remarkable escalation in understanding the anatomy and physiology of sleep/wake control mechanisms provides new opportunities to modify the neurobiology of sleep and wake-related behaviors in novel and exciting ways. In parallel, expansion of sleep research into novel interfaces between sleep-wake biology and disease states is revealing additional extensive implications of lost sleep. Current investigational and conventional pharmacological approaches for the treatment of sleep and wake disorders are discussed based on their mechanism of action within the CNS and their effect on sleep and wake. This review of recent sleep biology and sleep pharmacology peers into the future of sleep therapeutics to highlight both mechanistic safety and functional outcomes as key for differentiating

  2. Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma

    PubMed Central

    Favoni, Roberto E; Daga, Antonio; Malatesta, Paolo; Florio, Tullio

    2012-01-01

    The incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up-to-date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum derivatives and pemetrexed or raltitrexed, as preferred first-line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy-resistant disease. Over these foundations, several promising studies are ongoing at preclinical level and novel molecules are currently under evaluation as well. Yet, established tumour cell lines, used for decades to investigate the efficacy of anticancer agents, although still the main source of drug efficacy studies, after long-term cultures tend to biologically diverge from the original tumour, limiting the predictive potential of in vivo efficacy. Cancer stem cells (CSCs), a subpopulation of malignant cells capable of self-renewal and multilineage differentiation, are believed to play an essential role in cancer initiation, growth, metastasization and relapse, being responsible of chemo- and radiotherapy refractoriness. According to the current carcinogenesis theory, CSCs represent the tumour-initiating cell (TIC) fraction, the only clonogenic subpopulation able to originate a tumour mass. Consequently, the recently described isolation of TICs from hMPM, the proposed main pharmacological target for novel antitumoural drugs, may contribute to better dissect the biology and multidrug resistance pathways controlling hMPM growth. PMID:22289125

  3. [Pharmacological treatment strategy and mirror visual feedback treatment for neuropathic pain].

    PubMed

    Sumitani, Masahiko; Miyauchi, Satoru; Yamada, Yoshitsugu

    2012-11-01

    Neuropathic pain is a debilitating condition, and pharmacotherapy is the most established treatment strategy. A variety of pharmacotherapies is used for neuropathic pain management: however, pharmacotherapies with evidence for analgesic potency are less common. Several pharmacotherapeutic treatment guidelines for neuropathic pain treatment recommend the first- to third-line drugs on the basis of evidence-based medicine; however, neuropathic pain is often resistant to pharmacotherapies. We have treated pharmacotherapy-resistant neuropathic pain with neurorehabilitation techniques such as mirror visual feedback (MVF) treatment. Further to our clinical experience using MVF, we discuss the cerebral mechanism associated with neuropathic pain in this study. PMID:23131739

  4. Postpartum and nonpostpartum depression: differences in presentation and response to pharmacologic treatment.

    PubMed

    Hendrick, V; Altshuler, L; Strouse, T; Grosser, S

    2000-01-01

    Following childbirth, major depression (postpartum depression) affects approximately 8-12% of new mothers. However, little is known about the pharmacological management of postpartum depression, and no studies to date have assessed differences in treatment response between women with postpartum and nonpostpartum major depression. The authors reviewed the records of 26 women with postpartum major depression and 25 women with major depression unrelated to childbearing (nonpostpartum depression) who presented to them for treatment over a 4-year period. Compared with the nonpostpartum depressed patients, the postpartum depressed women were significantly more likely to present with anxious features. Also, cases of postpartum depression were more severe than cases of nonpostpartum depression. While the postpartum patients were equally as likely to recover (as defined by a Clinical Global Impression score of 1 or 2) compared to the nonpostpartum-depressed patients, their time to response was significantly longer. By 3 weeks of pharmacotherapy, 75% of the nonpostpartum cases had recovered, in contrast to only 36% of the postpartum cases. Further, postpartum patients were significantly more likely to be receiving more than one antidepressant agent at the time of response to treatment. Length of depression prior to treatment did not explain the difference in treatment response. Presence of depressive symptoms during pregnancy and timing of onset of the depression (before vs. after 4 weeks of delivery) did not affect likelihood of treatment response in this sample. Women with postpartum depression appear to be significantly more likely than the nonpostpartum women to present with anxious features, take longer to respond to pharmacotherapy for depression, and require more antidepressant agents at the time of response to treatment. PMID:10812531

  5. Opioid antagonists for pharmacological treatment of alcohol dependence - a critical review.

    PubMed

    Soyka, Michael; Rösner, Susanne

    2008-11-01

    Alcohol dependence is a widespread psychiatric disorder. While relapse prevention therapy in alcoholism was exclusively dominated by social and psychological treatments for many years, in the last decades the benefits of pharmacological agents for the rehabilitation treatment in alcoholism have become increasingly evident. Naltrexone, an opiate receptor antagonist, blocks the pleasant and reinforcing effects of alcohol by preventing the stimulation of opioid receptors and the reduction of dopamine release in the ventral tegmental area (VTA). Clinical evidence about the effectiveness of the substance is not always consistent, but meta-analyses confirm naltrexone's effect on the risk of heavy drinking. Evidence about the abstinence-maintaining effects of the substance comes from a relatively small database and needs further investigation. The evaluation of differential effects of naltrexone depending on biological or psychological profiles, which could further enhance the effectiveness of treatments for alcohol dependence, remains a challenge. Nalmefene, another opioid antagonist, as well as naltrexone depot, a sustained release formulation of naltrexone, are further promising strategies for the treatment of alcohol dependence. The review at hand gives on overview of the current evidence on opioid antagonists for the treatment of alcohol dependence regarding the possible mechanism of action, the substances' safety profiles and their effectiveness. The corresponding evidence is critically reviewed taking into consideration the influence of the study design on the magnitude and consistency of effect sizes as well the impact of patient characteristics on the response to the treatment with opioid antagonists. Future studies on the role of different subtypes of alcoholics according to their genetic or psychological profile to explain or even predict the effects of opioid antagonists in the treatment of alcohol dependence are needed. PMID:19630726

  6. A novel method for imaging the pharmacological effects of antibiotic treatment on Clostridium difficile.

    PubMed

    Endres, Bradley T; Bassères, Eugénie; Memariani, Ali; Chang, Long; Alam, M Jahangir; Vickers, Richard J; Kakadiaris, Ioannis A; Garey, Kevin W

    2016-08-01

    Clostridium difficile is a significant cause of nosocomial-acquired infection that results in severe diarrhea and can lead to mortality. Treatment options for C. difficile infection (CDI) are limited, however, new antibiotics are being developed. Current methods for determining efficacy of experimental antibiotics on C. difficile involve antibiotic killing rates and do not give insight into the drug's pharmacologic effects. Considering this, we hypothesized that by using scanning electron microscopy (SEM) in tandem to drug killing curves, we would be able to determine efficacy and visualize the phenotypic response to drug treatment. To test this hypothesis, supraMIC kill curves were conducted using vancomycin, metronidazole, fidaxomicin, and ridinilazole. Following collection, cells were either plated or imaged using a scanning electron microscope (SEM). Consistent with previous reports, we found that the tested antibiotics had significant bactericidal activity at supraMIC concentrations. By SEM imaging and using a semi-automatic pipeline for image analysis, we were able to determine that vancomycin and to a lesser extent fidaxomicin and ridinilazole significantly affected the cell wall, whereas metronidazole, fidaxomicin, and ridinilazole had significant effects on cell length suggesting a metabolic effect. While the phenotypic response to drug treatment has not been documented previously in this manner, the results observed are consistent with the drug's mechanism of action. These techniques demonstrate the versatility and reliability of imaging and measurements that could be applied to other experimental compounds. We believe the strategies laid out here are vital for characterizing new antibiotics in development for treating CDI. PMID:27108094

  7. A Systematic Review of Pharmacological Treatments of Pain Following Spinal Cord Injury

    PubMed Central

    Teasell, Robert W.; Mehta, Swati; Aubut, Jo-Anne L.; Foulon, Brianne; Wolfe, Dalton L.; Hsieh, Jane T.C.; Townson, Andrea F.; Short, Christine

    2011-01-01

    Objective To conduct a systematic review of published research on the pharmacological treatment of pain after spinal cord injury (SCI). Data Sources Medline, CINAHL, EMBASE and PsycINFO databases were searched for articles published 1980 to June 2009 addressing the treatment of pain post SCI. Randomized controlled trials (RCTs) were assessed for methodological quality using the PEDro assessment scale, while non-RCTs were assessed using the Downs and Black evaluation tool. A level of evidence was assigned to each intervention using a modified Sackett scale. Study Selection The review included randomized controlled trials and non-randomized controlled trials which included prospective controlled trials, cohort, case series, case-control, pre-post and post studies. Case studies were included only when there were no other studies found. Data Extraction Data extracted included the PEDro or Downs and Black score, the type of study, a brief summary of intervention outcomes, type of pain, type of pain scale and the study findings.. Data Synthesis Articles selected for this particular review evaluated different interventions in the pharmacological management of pain post SCI. 28 studies met inclusion criteria: there were 21 randomized controlled trials of these 19 had Level 1 evidence. Treatments were divided into five categories: anticonvulsants, antidepressants, analgesics, cannabinoids and antispasticity medications. Conclusions Most studies did not specify participants’ types of pain; hence making it difficult to identify the type of pain being targeted by the treatment. Anticonvulsant and analgesic drugs had the highest levels of evidence and were the drugs most often studied. Gabapentin and pregabalin had strong evidence (five Level 1 RCTs) for effectiveness in treating post-SCI neuropathic pain, as did intravenous analgesics (lidocaine, ketamine and morphine) but the latter only had short term benefits. Tricyclic antidepressants only showed benefit for neuropathic

  8. Pharmacological agents in the treatment of venous disease: an update of the available evidence.

    PubMed

    Gohel, Manjit S; Davies, Alun H

    2009-07-01

    Varicose veins and the complications of venous disease are thought to affect over a quarter of the adult population and the management of these conditions are a major cause of health service expense. Advances in the understanding of venous pathophysiology have highlighted numerous potential targets for pharmacotherapy. This review considers the evidence for pharmacological agents used for the treatment of chronic venous disease. A literature search using Pubmed, Embase and Cinahl databases was performed. The initial search terms 'varicose vein', 'venous ulcer' and 'venous disease' were used with appropriate search limits to identify prospective studies of pharmacotherapy in venous disease. A wide range of venoactive and non-venoactive drugs have been studied in patients with venous disease. The use of micronized purified flavonoid fraction (Daflon) can reduce symptoms of pain, heaviness and oedema in patients with venous reflux and a recent meta-analysis concluded that Daflon improves healing in patients with venous ulceration treated with compression. Pentoxifylline may be a useful adjunct to compression therapy for patients with venous ulceration. Oxerutins and calcium dobesilate may be of benefit in reducing oedema and rutosides may help to relieve the symptoms of varicose veins in pregnancy. The clinical benefits of other medications remain unproven. Although numerous pharmacological agents have been proposed and studied, Daflon has demonstrated the greatest clinical benefits in patients with venous disease. Further research is needed to define the role of venoactive drugs in clinical care and improve our understanding of the pathophysiology of venous disease to help identify new therapeutic avenues. PMID:19601855

  9. Pharmacologic Treatment of First-Episode Schizophrenia: A Review of the Literature

    PubMed Central

    Nandhra, Harpal Sing; Singh, Swaran P.

    2012-01-01

    Objective: To review the evidence base for the efficacy and tolerability of antipsychotic medication for the treatment of the first episode of schizophrenia. Data Source: MEDLINE databases were searched for published articles in English over the last 25 years, from January 1986 to January 2011, on choice of antipsychotic treatment for the first episode of schizophrenia, with an emphasis on efficacy and tolerability of antipsychotic drugs in the acute phase of psychotic illness. Study Selection: The keywords antipsychotic drugs and schizophrenia were used in combination with drug treatment, pharmacologic treatment, efficacy, and tolerability in addition to atypical antipsychotics, first-generation antipsychotics, second-generation antipsychotics, first-episode psychosis, and acute psychotic episode. Data Synthesis: At present, there is no convincing evidence to guide clinicians in choosing a single first-line antipsychotic that is effective in treating the positive and negative symptoms of the first episode of schizophrenia. Even though second-generation antipsychotic drugs offer potential benefits in terms of less extrapyramidal side effects and some benefits in treating negative, affective, and cognitive symptoms, these drugs are not without their own side effects. Conclusions: With the introduction of a number of second-generation antipsychotic drugs there have been significant advances in antipsychotic drug treatment over the last decade. Despite these advances, there are still a number of limitations in continued use of some antipsychotic medications due to their efficacy and tolerability issues in the acute and early maintenance phases of psychosis. Active research in this area would provide more promising results of improved efficacy and tolerability of antipsychotic medication. PMID:22690369

  10. Validation of the AQT Color-Form Additive Model for Screening and Monitoring Pharmacological Treatment of ADHD

    ERIC Educational Resources Information Center

    Nielsen, Niels Peter; Wiig, Elisabeth Hemmersam

    2013-01-01

    Objective:This retrospective study used A Quick Test of Cognitive Speed (AQT) processing-speed and efficiency measures for evaluating sensitivity and monitoring effects during pharmacological treatment of adults with ADHD. Method: Color (C), form (F), and color-form (CF) combination naming were administered to 69 adults during outpatient…

  11. Pharmacological approach to the treatment of long and short QT syndromes☆

    PubMed Central

    Patel, Chinmay; Antzelevitch, Charles

    2008-01-01

    Inherited channelopathies have received increasing attention in recent years. The past decade has witnessed impressive progress in our understanding of the molecular and cellular basis of arrhythmogenesis associated with inherited channelopathies. An imbalance in ionic forces induced by these channelopathies affects the duration of ventricular repolarization and amplifies the intrinsic electrical heterogeneity of the myocardium, creating an arrhythmogenic milieu. Today, many of the channelopathies have been linked to mutations in specific genes encoding either components of ion channels or membrane or regulatory proteins. Many of the channelopathies are genetically heterogeneous with a variable degree of expression of the disease. Defining the molecular basis of channelopathies can have a profound impact on patient management, particularly in cases in which genotype-specific pharmacotherapy is available. The long QT syndrome (LQTS) is one of the first identified and most studied channelopathies where abnormal prolongation of ventricular repolarization predisposes an individual to life threatening ventricular arrhythmia called Torsade de Pointes. On the other hand of the spectrum, molecular defects favoring premature repolarization lead to Short QT syndrome (SQTS), a recently described inherited channelopathy. Both of these channelopathies are associated with a high risk of sudden cardiac death due to malignant ventricular arrhythmia. Whereas pharmacological therapy is first line treatment for LQTS, defibrillators are considered as primary treatment for SQTS. This review provides a comprehensive review of the molecular genetics, clinical features, genotype–phenotype correlations and genotype-specific approach to pharmacotherapy of these two mirror-image channelopathies, SQTS and LQTS. PMID:18378319

  12. The clinical pharmacology and pharmacokinetics of ulipristal acetate for the treatment of uterine fibroids.

    PubMed

    Pohl, Oliver; Zobrist, R Howard; Gotteland, Jean-Pierre

    2015-04-01

    Uterine fibroids are benign hormone-sensitive tumors of uterine smooth muscle cells leading to heavy menstrual bleeding and pelvic pain. Ulipristal acetate (UPA) is an emerging medical treatment of fibroids with the potential to be used for long-term treatment. In this context, the present article summarizes UPA's main clinical pharmacology and pharmacokinetic (PK) properties. Ulipristal acetate has good oral bioavailability and a half-life allowing one single oral administration per day for the management of fibroids. As a steroid, UPA is a substrate for cytochrome P450 (CYP) 3A4 but does not act as an inducer or inhibitor of the CYP system or transporter proteins. With the exception of drugs modulating CYP3A4 activity, risks of drug-drug interactions with UPA are unlikely. In conclusion, besides its pharmacodynamic characteristics, UPA shows favorable PK properties that contribute to a good efficacy-safety ratio for the long-term management of uterine fibroids in clinical practice. PMID:25228633

  13. Sodium Oxybate: A Potential New Pharmacological Option for the Treatment of Fibromyalgia Syndrome

    PubMed Central

    Swick, Todd J.

    2011-01-01

    Fibromyalgia syndrome (FMS) is a common disorder, characterized by diffuse pain and tenderness, stiffness, fatigue, affective disorders and significant sleep pathology. A new set of diagnostic criteria have been developed which should make it easier for a busy clinician to diagnose the condition. US Food and Drug Administration (FDA) approved medications for the treatment of FMS have, for the most part, been geared to modulate the pain pathways to give the patient some degree of relief. A different kind of pharmacological agent, sodium oxybate (SXB), is described that is currently approved for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. SXB, an endogenous metabolite of the inhibitory neurotransmitter gamma-hydroxybutyrate, is thought to act independently as a neurotransmitter with a presumed ability to modulate numerous other central nervous system neurotransmitters. In addition SXB has been shown to robustly increase slow wave sleep and decrease sleep fragmentation. Several large clinical trials have demonstrated SXB's ability to statistically improve pain, fatigue and a wide array of quality of life measurements of patients with fibromyalgia. SXB is not FDA approved to treat fibromyalgia. PMID:22870476

  14.  NASH: A glance at the landscape of pharmacological treatment.

    PubMed

    Brodosi, Lucia; Marchignoli, Francesca; Petroni, Maria Letizia; Marchesini, Giulio

    2016-01-01

     The role of nonalcoholic fatty liver disease, namely nonalcoholic steatohepatitis (NASH), as risk factor for liver- and non-liver-related morbidity and mortality has been extensively reported. In addition to lifestyle changes, capable of removing the metabolic factors driving disease progression, there is an urgent need for drugs able to reduce hepatic necroinflammation without worsening of fibrosis. This goal is considered by regulatory agencies as surrogate marker to define the effectiveness in pharmacological compounds in NASH, and fast-track approval was granted by the Food and Drug Administration in consideration of disease severity and unmet medical needs. Several compounds are in the pipeline of pharmaceutical industries and are being studied in phase II trials, but only a few (obeticholic acid, elafibranor) have started phase III trials. This concise review is intended to offer a systematic analysis of the most promising therapeutic intervention in NASH. In conclusion, there is reasonable expectation that drug may help curb the burden of NASH, and we look forward to obtaining solid data on their long-term safety and effectiveness. However, we should not forget that behavioral interventions remain a mandatory background treatment, able to stop disease progression in compliant overweight/ obese patients, with results that compare favorably with - and add to - the beneficial effects of drug treatment. PMID:27493105

  15. Do pharmacological and behavioral interventions differentially affect treatment outcome for children with social phobia?

    PubMed

    Scharfstein, Lindsay A; Beidel, Deborah C; Finnell, Laura Rendon; Distler, Aaron; Carter, Nathan T

    2011-09-01

    In a randomized trial for children with social phobia (SP), Social Effectiveness Therapy for Children (SET-C; a treatment consisting of exposure and social skills training) and fluoxetine were more effective than pill placebo in reducing social distress and behavioral avoidance, but only SET-C demonstrated significantly improved overall social skill and social competence. In the current study, the authors examined the specific social skills enhanced by SET-C using a recently developed coding schema. At posttreatment, children treated with SET-C displayed a more effective ability to manage the conversational topic (pragmatic social behaviors) and more appropriate motor movement, facial orientation, and posture (paralinguistic social behaviors) than children treated with fluoxetine or placebo. In contrast, children treated with fluoxetine displayed no more pragmatic or paralinguistic skill than children given a pill placebo. There were no group differences on ratings of voice volume and vocal inflection (speech and prosodic social behaviors). Furthermore, only children treated with SET-C improved from pre- to posttreatment on all three skill variables. Findings suggest that pharmacological interventions that only target reduction in anxious arousal may not have an impact on social skill deficits and may not be adequate to optimally treat SP. The relationship of social skill to social avoidance and the importance of social skills training to enhance social competence in the treatment of childhood SP are discussed. PMID:21586501

  16. Pharmacological approach to the treatment of long and short QT syndromes.

    PubMed

    Patel, Chinmay; Antzelevitch, Charles

    2008-04-01

    Inherited channelopathies have received increasing attention in recent years. The past decade has witnessed impressive progress in our understanding of the molecular and cellular basis of arrhythmogenesis associated with inherited channelopathies. An imbalance in ionic forces induced by these channelopathies affects the duration of ventricular repolarization and amplifies the intrinsic electrical heterogeneity of the myocardium, creating an arrhythmogenic milieu. Today, many of the channelopathies have been linked to mutations in specific genes encoding either components of ion channels or membrane or regulatory proteins. Many of the channelopathies are genetically heterogeneous with a variable degree of expression of the disease. Defining the molecular basis of channelopathies can have a profound impact on patient management, particularly in cases in which genotype-specific pharmacotherapy is available. The long QT syndrome (LQTS) is one of the first identified and most studied channelopathies where abnormal prolongation of ventricular repolarization predisposes an individual to life threatening ventricular arrhythmia called Torsade de Pointes. On the other hand of the spectrum, molecular defects favoring premature repolarization lead to Short QT syndrome (SQTS), a recently described inherited channelopathy. Both of these channelopathies are associated with a high risk of sudden cardiac death due to malignant ventricular arrhythmia. Whereas pharmacological therapy is first line treatment for LQTS, defibrillators are considered as primary treatment for SQTS. This review provides a comprehensive review of the molecular genetics, clinical features, genotype-phenotype correlations and genotype-specific approach to pharmacotherapy of these two mirror-image channelopathies, SQTS and LQTS. PMID:18378319

  17. Medical treatment overview: traditional and novel psycho-pharmacological and complementary and alternative medications

    PubMed Central

    Anagnostou, Evdokia; Hansen, Robin

    2016-01-01

    Purpose of review Up to 35% of children and youth with autism spectrum disorder (ASD) receive at least one psychotropic medication. 50–70% of this population also receives biologically based complementary and alternative medicine (CAM). The data evaluating such practices are being reviewed. Recent findings There are accumulating data to suggest that atypical antipsychotics and stimulants may be useful for the treatment of irritability and hyperactivity in children and youth with ASD. The data for the use of selective serotonin reuptake inhibitors are less promising. New avenues of pharmacologic research targeting molecular targets identified by genomics, animal models and neuropathology are being evaluated. Areas of interest include glutamate/gamma-aminobutyric acid systems, neuropeptides such as oxytocin, and immune dysfunction, among others. In the case of biologically based CAM, a few compounds have been shown to be well tolerated, although efficacy is still being evaluated, such as melatonin, certain vitamins, and omega 3 fatty acids. Others have safety concerns without demonstrated efficacy, such as chelation therapies. Summary Accumulating data suggest a series of existing medications may be useful in ASD and large randomized clinical trials are necessary to evaluate safety and efficacy of both pharmaceuticals and alternative treatments. PMID:22001766

  18. Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people.

    PubMed

    Sahakian, Barbara J; Morein-Zamir, Sharon

    2015-04-01

    Neuropsychiatric disorders typically manifest as problems with attentional biases, aberrant learning, dysfunctional reward systems, and an absence of top-down cognitive control by the prefrontal cortex. In view of the cost of common mental health disorders, in terms of distress to the individual and family in addition to the financial cost to society and governments, new developments for treatments that address cognitive dysfunction should be a priority so that all members of society can flourish. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used as treatments for the cognitive symptoms of Alzheimer's disease and attention deficit hyperactivity disorder. However, these drugs and others, including modafinil, are being increasingly used by healthy people for enhancement purposes. Importantly for ethical and safety reasons, the drivers for this increasing lifestyle use of so-called smart drugs by healthy people should be considered and discussions must occur about how to ensure present and future pharmacological cognitive enhancers are used for the benefit of society. PMID:26360089

  19. The Clinical Pharmacology and Pharmacokinetics of Ulipristal Acetate for the Treatment of Uterine Fibroids

    PubMed Central

    Pohl, Oliver; Zobrist, R. Howard

    2014-01-01

    Uterine fibroids are benign hormone-sensitive tumors of uterine smooth muscle cells leading to heavy menstrual bleeding and pelvic pain. Ulipristal acetate (UPA) is an emerging medical treatment of fibroids with the potential to be used for long-term treatment. In this context, the present article summarizes UPA’s main clinical pharmacology and pharmacokinetic (PK) properties. Ulipristal acetate has good oral bioavailability and a half-life allowing one single oral administration per day for the management of fibroids. As a steroid, UPA is a substrate for cytochrome P450 (CYP) 3A4 but does not act as an inducer or inhibitor of the CYP system or transporter proteins. With the exception of drugs modulating CYP3A4 activity, risks of drug–drug interactions with UPA are unlikely. In conclusion, besides its pharmacodynamic characteristics, UPA shows favorable PK properties that contribute to a good efficacy–safety ratio for the long-term management of uterine fibroids in clinical practice. PMID:25228633

  20. Aspects of the non-pharmacological treatment of irritable bowel syndrome.

    PubMed

    Eriksson, Elsa Maria; Andrén, Kristina Ingrid; Kurlberg, Göran Karl; Eriksson, Henry Ture

    2015-10-28

    Irritable bowel syndrome (IBS) is one of the most commonly diagnosed gastrointestinal conditions. It represents a significant healthcare burden and remains a clinical challenge. Over the years IBS has been described from a variety of different perspectives; from a strict illness of the gastrointestinal tract (medical model) to a more complex multi-symptomatic disorder of the brain-gut axis (biopsychosocial/psychosomatic model). In this article we present aspects of the pathophysiology and the non-pharmacological treatment of IBS based on current knowledge. Effects of conditioned stress and/or traumatic influences on the emotional system (top-down) as well as effects on the intestine through stressors, infection, inflammation, food and dysbiosis (bottom-up) can affect brain-gut communication and result in dysregulation of the autonomic nervous system (ANS), playing an important role in the pathophysiology of IBS. Conditioned stress together with dysregulation of the autonomic nervous system and the emotional system may involve reactions in which the distress inside the body is not recognized due to low body awareness. This may explain why patients have difficulty identifying their symptoms despite dysfunction in muscle tension, movement patterns, and posture and biochemical functions in addition to gastrointestinal symptoms. IBS shares many features with other idiopathic conditions, such as fibromyalgia, chronic fatigue syndrome and somatoform disorders. The key to effective treatment is a thorough examination, including a gastroenterological examination to exclude other diseases along with an assessment of body awareness by a body-mind therapist. The literature suggests that early interdisciplinary diagnostic co-operation between gastroenterologists and body-mind therapists is necessary. Re-establishing balance in the ANS is an important component of IBS treatment. This article discusses the current knowledge of body-mind treatment, addressing the topic from a

  1. Aspects of the non-pharmacological treatment of irritable bowel syndrome

    PubMed Central

    Eriksson, Elsa Maria; Andrén, Kristina Ingrid; Kurlberg, Göran Karl; Eriksson, Henry Ture

    2015-01-01

    Irritable bowel syndrome (IBS) is one of the most commonly diagnosed gastrointestinal conditions. It represents a significant healthcare burden and remains a clinical challenge. Over the years IBS has been described from a variety of different perspectives; from a strict illness of the gastrointestinal tract (medical model) to a more complex multi-symptomatic disorder of the brain-gut axis (biopsychosocial/psychosomatic model). In this article we present aspects of the pathophysiology and the non-pharmacological treatment of IBS based on current knowledge. Effects of conditioned stress and/or traumatic influences on the emotional system (top-down) as well as effects on the intestine through stressors, infection, inflammation, food and dysbiosis (bottom-up) can affect brain-gut communication and result in dysregulation of the autonomic nervous system (ANS), playing an important role in the pathophysiology of IBS. Conditioned stress together with dysregulation of the autonomic nervous system and the emotional system may involve reactions in which the distress inside the body is not recognized due to low body awareness. This may explain why patients have difficulty identifying their symptoms despite dysfunction in muscle tension, movement patterns, and posture and biochemical functions in addition to gastrointestinal symptoms. IBS shares many features with other idiopathic conditions, such as fibromyalgia, chronic fatigue syndrome and somatoform disorders. The key to effective treatment is a thorough examination, including a gastroenterological examination to exclude other diseases along with an assessment of body awareness by a body-mind therapist. The literature suggests that early interdisciplinary diagnostic co-operation between gastroenterologists and body-mind therapists is necessary. Re-establishing balance in the ANS is an important component of IBS treatment. This article discusses the current knowledge of body-mind treatment, addressing the topic from a

  2. Pharmacological Treatment of Sleep Disturbance in Developmental Disabilities: A Review of the Literature

    ERIC Educational Resources Information Center

    Hollway, Jill A.; Aman, Michael G.

    2011-01-01

    Sleep disturbance is a common problem in children with developmental disabilities. Effective pharmacologic interventions are needed to ameliorate sleep problems that persist when behavior therapy alone is insufficient. The aim of the present study was to provide an overview of the quantity and quality of pharmacologic research targeting sleep in…

  3. The role of dental therapists in pharmacological and non-pharmacological treatment of anxious and phobic patients.

    PubMed

    MacLeavey, Christine

    2013-01-01

    Dental Therapists are in a prime position to be involved with the management of anxious and phobic patients. They earn less than dentists and are therefore a more cost-effective way of providing specialised care for anxious patients. Dental Therapists can spend more time educating and acclimatising these patients, do most if not all of the patient's treatment, only referring back to the dentist for RCT, crown/bridgework/dentures and permanent extractions. Ultimately this means that the patient receives high quality continuity of care. Treating anxious and phobic patients is time-consuming but ultimately very rewarding. If handled correctly and sensitively the anxious and phobic patient will not always be anxious or phobic, in the same way that children won't always be children. Dental Therapists can now extend their duties to include Relative Analgesia. This should enhance their employability and role within the dental team especially in the management of anxious and phobic patients. Employing a therapist with a toolbox of techniques at their disposal can be seen as part of a long-term practice plan to ensure that anxious and phobic patients become rehabilitated, happy, compliant and loyal to the practice! In fact .... the sort of patients every dentist really wants to see. PMID:23544223

  4. Regulated recycling of mutant CFTR is partially restored by pharmacological treatment.

    PubMed

    Holleran, John P; Zeng, Jianxin; Frizzell, Raymond A; Watkins, Simon C

    2013-06-15

    Efficient trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) to and from the cell surface is essential for maintaining channel density at the plasma membrane (PM) and ensuring proper physiological activity. The most common mutation, F508del, exhibits reduced surface expression and impaired function despite treatment with currently available pharmacological small molecules, called correctors. To gain more detailed insight into whether CFTR enters compartments that allow corrector stabilization in the cell periphery, we investigated the peripheral trafficking itineraries and kinetics of wild type (WT) and F508del in living cells using high-speed fluorescence microscopy together with fluorogen activating protein detection. We directly visualized internalization and accumulation of CFTR WT from the PM to a perinuclear compartment that colocalized with the endosomal recycling compartment (ERC) markers Rab11 and EHD1, reaching steady-state distribution by 25 minutes. Stimulation by protein kinase A (PKA) depleted this intracellular pool and redistributed CFTR channels to the cell surface, elicited by reduced endocytosis and active translocation to the PM. Corrector or temperature rescue of F508del also resulted in targeting to the ERC and exhibited subsequent PKA-stimulated trafficking to the PM. Corrector treatment (24 hours) led to persistent residence of F508del in the ERC, while thermally destabilized F508del was targeted to lysosomal compartments by 3 hours. Acute addition of individual correctors, C4 or C18, acted on peripheral trafficking steps to partially block lysosomal targeting of thermally destabilized F508del. Taken together, corrector treatment redirects F508del trafficking from a degradative pathway to a regulated recycling route, and proteins that mediate this process become potential targets for improving the efficacy of current and future correctors. PMID:23572510

  5. Raynaud's phenomenon and digital ischaemia--pharmacologic approach and alternative treatment options.

    PubMed

    Linnemann, Birgit; Erbe, Matthias

    2016-01-01

    The primary goal of therapy is to reduce the frequency and intensity of Raynaud's attacks and to minimize the related morbidity rather than to cure the underlying condition. Treatment strategies depend on whether Raynaud's phenomenon (RP) is primary or secondary. All patients should be instructed about general measures to maintain body warmth and to avoid triggers of RP attacks. Pharmacologic intervention can be useful for patients with severe and frequent RP episodes that impair the patient's quality of life. Calcium channel blockers are currently the most prescribed and studied medications for this purpose. There has been limited evidence for the efficacy of alpha-1-adrenergic receptor antagonists, angiotensin receptor blockers, topical nitrates or fluoxetine to treat RP. The intravenously administered prostacyclin analogue iloprost can reduce the frequency and severity of RP attacks and is considered a second-line therapy in patients with markedly impaired quality of life, critical digital ischaemia and skin ulcers who are at risk for substantial tissue loss and amputation. Phosphodiesterase inhibitors (e.g., sildenafil) can also improve RP symptoms and ulcer healing whereas endothelin-1 receptor antagonists (e.g., bosentan) are mainly considered treatment options in secondary prevention for patients with digital skin ulcers related to systemic sclerosis. However, their use in clinical practice has been limited by their high cost. Antiplatelet therapy with low-dose aspirin is recommended for all patients who suffer from secondary RP due to ischaemia caused by structural vessel damage. Anticoagulant therapy can be considered during the acute phase of digital ischaemia in patients with suspected vascular occlusive disease attributed to the occurrence of new thromboses. In patients with critical digital ischaemia, consideration should be given to hospitalisation, optimisation of medical treatment in accordance with the underlying disease and evaluation for a

  6. [Non-pharmacological treatment of ventricular tachycardia (anti-arrhythmic surgery excluded)].

    PubMed

    Touboul, P

    1993-05-01

    There has been real change in the treatment of VT in recent years including the promotion of non-medical methods. In the large group of non-responders to medical therapy, only a minority offers possibilities of radical surgical treatment of VT. In the others, two options remain: ablative methods and implantable automatic cardioverter defibrillators. The destruction of foci of tachycardia by catheterisation necessitates prior investigation of the ventricular endocardium with recordings of endocardial electrograms during VT. Criteria defining the zone for ablation are two-fold: either the zone of earliest endocardial depolarisation or the exit zone (generally preceding the tachycardia QRS complexes by 20 to 30 ms). The second is the zone of slow conduction which corresponds to the cardiac substrate in which the tachycardia arises. In the absence of satisfactory mapping, localisation of the ablation target may be performed by stimulating the endocardium at different points with the aim of reproducing the tachycardia QRS complexes. Two types of physical agents have been used for ablation: high energy electric shocks and, at present, radiofrequency currents. Complications of the procedure are rare: thromboembolism, cardiac rupture, cardiogenic shock in patients with initially poor hemodynamic conditions. Prevention of VT is obtained in over half the cases providing complementary antiarrhythmic therapy is prescribed. The other alternative is the implantable automatic defibrillator which is tending to take over the leading role in non-pharmacological treatment of VT. At first, these devices were exclusively defibrillators but nowadays they have anti-tachycardia functions which widen the indications to include subjects with sustained VT even in the absence of cardiac arrest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8267510

  7. Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment)

    PubMed Central

    Nakamura, Tadakatsu; Kubota, Tomoko; Iwakaji, Atsushi; Imada, Masayoshi; Kapás, Margit; Morio, Yasunori

    2016-01-01

    Purpose Cariprazine is a potent dopamine D3-preferring D3/D2 receptor partial agonist in development for the treatment of schizophrenia, bipolar mania, and depression. Pharmacokinetics of cariprazine and the two clinically relevant metabolites (desmethyl- and didesmethyl-cariprazine) was evaluated in a clinical pharmacology study. Methods This was a multicenter, randomized, open-label, parallel-group, fixed-dose (3, 6, or 9 mg/day) study of 28-week duration (≤4-week observation, 12-week open-label treatment, and 12-week follow-up). Once-daily cariprazine was administered to 38 adult patients with schizophrenia. The pharmacokinetics of cariprazine, metabolites, and total active moieties (sum of cariprazine and two metabolites) was evaluated; efficacy and safety were also assessed. Results Steady state was reached within 1–2 weeks for cariprazine and desmethyl-cariprazine, 4 weeks for didesmethyl-cariprazine, and 3 weeks for total active moieties. Cariprazine and desmethyl-cariprazine levels decreased >90% within 1 week after the last dose, didesmethyl-cariprazine decreased ~50% at 1 week, and total active moieties decreased ~90% within 4 weeks. Terminal half-lives of cariprazine, desmethyl-cariprazine, and didesmethyl-cariprazine ranged from 31.6 to 68.4, 29.7 to 37.5, and 314 to 446 hours, respectively. Effective half-life (calculated from time to steady state) of total active moieties was ~1 week. Incidence of treatment-emergent adverse events was 97.4%; 15.8% of patients discontinued due to adverse events. No abnormal laboratory values or major differences from baseline in extrapyramidal symptoms were observed. Conclusion Cariprazine and its active metabolites reached steady state within 4 weeks, and exposure was dose proportional over the range of 3–9 mg/day. Once-daily cariprazine was generally well tolerated in adult patients with schizophrenia. PMID:26834462

  8. Pharmacologic treatment approaches for children and adolescents with posttraumatic stress disorder.

    PubMed

    Donnelly, Craig L

    2003-04-01

    should target anxiety, mood, and reexperiencing symptoms. Adrenergic agents, such as clonidine, used either alone or in combination with an SSRI may be useful when symptoms of hyperarousal and impulsivity are problematic. Supplementing with a mood stabilizer may be necessary in severe affective dyscontrol. Similarly, introduction of an atypical neuroleptic agent may be necessary in cases of severe self-injurious behavior, dissociation, psychosis, or aggression. Comorbid conditions such as ADHD should be targeted with pharmacotherapy known to be effective, such as psychostimulants or newer agents such as atomoxetine. Pharmacologic treatment of PTSD in childhood is one approach to alleviating the acute and chronic symptoms of the disorder. Despite the lack of well-designed, randomized, controlled trials that support efficacy, medication can be used in a rational and safe manner. Reduction in even one disabling symptom, such as insomnia or hyperarousal, may have a positive ripple effect on a child's overall functioning. Pharmacotherapy is typically used as one component of a more comprehensive multiple modality treatment package, including psychoeducation of the parent and child, focused exposure-based psychotherapy with adjunctive family therapy when indicated, and long-term booster interventions that use an admixture of psychodynamic, cognitive-behavioral, and pharmacologic interventions. PMID:12725011

  9. Pharmacological, immunological, and gene targeting of the renin-angiotensin system for treatment of cardiovascular disease.

    PubMed

    Igic, Rajko; Behnia, Rahim

    2007-01-01

    Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not reduce cardiovascular disease risks to the levels in normotensive persons. Only two drug classes that inhibit or antagonize portions of the renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT(1) receptor) blockers, have protective and beneficial effects unrelated to the degree of blood pressure reduction. These drugs may prevent the blood pressure related functional and structural abnormalities of the cardiovascular system and reduce the end organ-damage. The first part of this review presents the components of the RAS, biological actions of angiotensin peptides, and the functions of the enzymes that generate and metabolize angiotensins, including the likely effect of manipulating them. Special attention is devoted to renin, ACE, ACE2, chymase, and neprilysin. The second part of this review presents the rationale for targeting the RAS, based on clinical studies of the ACE inhibitors and AT(1) receptor blockers. Finally, we present the investigational agents acting on the RAS that have a potential for clinical usage, and give the perspective of pharmacological, immunological and gene targeting of the RAS for treatment of cardiovascular disease. PMID:17504230

  10. Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex

    PubMed Central

    Neymotin, Samuel A.; Dura-Bernal, Salvador; Lakatos, Peter; Sanger, Terence D.; Lytton, William W.

    2016-01-01

    A large number of physiomic pathologies can produce hyperexcitability in cortex. Depending on severity, cortical hyperexcitability may manifest clinically as a hyperkinetic movement disorder or as epilpesy. We focus here on dystonia, a movement disorder that produces involuntary muscle contractions and involves pathology in multiple brain areas including basal ganglia, thalamus, cerebellum, and sensory and motor cortices. Most research in dystonia has focused on basal ganglia, while much pharmacological treatment is provided directly at muscles to prevent contraction. Motor cortex is another potential target for therapy that exhibits pathological dynamics in dystonia, including heightened activity and altered beta oscillations. We developed a multiscale model of primary motor cortex, ranging from molecular, up to cellular, and network levels, containing 1715 compartmental model neurons with multiple ion channels and intracellular molecular dynamics. We wired the model based on electrophysiological data obtained from mouse motor cortex circuit mapping experiments. We used the model to reproduce patterns of heightened activity seen in dystonia by applying independent random variations in parameters to identify pathological parameter sets. These models demonstrated degeneracy, meaning that there were many ways of obtaining the pathological syndrome. There was no single parameter alteration which would consistently distinguish pathological from physiological dynamics. At higher dimensions in parameter space, we were able to use support vector machines to distinguish the two patterns in different regions of space and thereby trace multitarget routes from dystonic to physiological dynamics. These results suggest the use of in silico models for discovery of multitarget drug cocktails. PMID:27378922

  11. Interaction between behavioral and pharmacological treatment strategies to decrease cocaine choice in rhesus monkeys.

    PubMed

    Banks, Matthew L; Blough, Bruce E; Negus, S Stevens

    2013-02-01

    Behavioral and pharmacotherapeutic approaches constitute two prominent strategies for treating cocaine dependence. This study investigated interactions between behavioral and pharmacological strategies in a preclinical model of cocaine vs food choice. Six rhesus monkeys, implanted with a chronic indwelling double-lumen venous catheter, initially responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and cocaine injections (0-0.1 mg/kg/injection, FR 10 schedule) during continuous 7-day treatment periods with saline or the agonist medication phenmetrazine (0.032-0.1 mg/kg/h). Subsequently, the FR response requirement for cocaine or food was varied (food, FR 100; cocaine, FR 1-100; cocaine, FR 10; food, FR 10-300), and effects of phenmetrazine on cocaine vs food choice were redetermined. Decreases in the cocaine FR or increases in the food FR resulted in leftward shifts in the cocaine choice dose-effect curve, whereas increases in the cocaine FR or decreases in the food FR resulted in rightward shifts in the cocaine choice dose-effect curve. The efficacy of phenmetrazine to decrease cocaine choice varied systematically as a function of the prevailing response requirements, such that phenmetrazine efficacy was greatest when cocaine choice was maintained by relatively low unit cocaine doses. These results suggest that efficacy of pharmacotherapies to modulate cocaine use can be influenced by behavioral contingencies of cocaine availability. Agonist medications may be most effective under contingencies that engender choice of relatively low cocaine doses. PMID:22968813

  12. Pharmacological profile of SSRIs and SNRIs in the treatment of eating disorders.

    PubMed

    Capasso, Anna; Petrella, Claudio; Milano, Walter

    2009-01-01

    Bulimia Nervosa (BN) and Binge Eating Disorder (BED) are some of the most common eating disorders (ED) in industrialized societies, characterized by uncontrolled binge eating and self-induced purging or other compensatory behaviours aiming to prevent body weight gain. It has been suggested that reduced serotonergic and noradrenergig tone triggers some of the cognitive and mood disturbances associated with ED. In fact in the active phase of ED the concentration of serotonin and noradrenaline in cerebral fluid is reduced. For these reasons, the pharmacologic treatment of ED consists mainly of selective serotonin reuptake inhibitors (SSRIs) or selective noradrenaline reuptake inhibitors (SNRIs) . At present, the physiologic basis of this disorder are not yet completely understood. In this review we evaluate several randomized controlled trials to compare the efficacy of several SSRIs and SNRIs in patients with a diagnosis of ED as defined by the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM IV]) These findings indicate that both SSRIs and SNRIs are well tolerated and reduce effectively the bulimic crisis and purging episodes in patients with ED. PMID:19149506

  13. Tics and other stereotyped movements as side effects of pharmacological treatment.

    PubMed

    Madruga-Garrido, Marcos; Mir, Pablo

    2013-01-01

    Tics and other stereotyped abnormal movements can be seen as adverse effects of some pharmacologic drugs. Among these drugs, antipsychotics may provoke tardive syndromes after a chronic exposure, primarily in the case of typical antipsychotics. These syndromes include tardive tics, tardive dyskinesia, or tardive akathisia, which present with tics or stereotyped movements as a clinical phenomenon. Psychostimulants (mainly methylphenidate) have traditionally been associated with the appearance of tics due to the increased dopamine activity caused by stimulants. Nevertheless, in recent years, several studies have concluded not only that methylphenidate does not exacerbate or reactivate tics but also that tics can improve with its use in patients with associated attention deficit and hyperactivity disorder and tic disorder. Antiepileptic drugs, although infrequently, can also induce tics, with carbamazepine and lamotrigine described as tic inducers. Other antiepileptics, including levetiracetam and topiramate, have been proposed as a potential treatment for tic disorders due to a positive effect on tics, especially in those with associated epileptic disorder. Clinical and therapeutic approaches to tics and stereotyped movements after exposure to antipsychotics, stimulants, and antiepileptic drugs will be reviewed in this chapter. PMID:24295631

  14. Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex.

    PubMed

    Neymotin, Samuel A; Dura-Bernal, Salvador; Lakatos, Peter; Sanger, Terence D; Lytton, William W

    2016-01-01

    A large number of physiomic pathologies can produce hyperexcitability in cortex. Depending on severity, cortical hyperexcitability may manifest clinically as a hyperkinetic movement disorder or as epilpesy. We focus here on dystonia, a movement disorder that produces involuntary muscle contractions and involves pathology in multiple brain areas including basal ganglia, thalamus, cerebellum, and sensory and motor cortices. Most research in dystonia has focused on basal ganglia, while much pharmacological treatment is provided directly at muscles to prevent contraction. Motor cortex is another potential target for therapy that exhibits pathological dynamics in dystonia, including heightened activity and altered beta oscillations. We developed a multiscale model of primary motor cortex, ranging from molecular, up to cellular, and network levels, containing 1715 compartmental model neurons with multiple ion channels and intracellular molecular dynamics. We wired the model based on electrophysiological data obtained from mouse motor cortex circuit mapping experiments. We used the model to reproduce patterns of heightened activity seen in dystonia by applying independent random variations in parameters to identify pathological parameter sets. These models demonstrated degeneracy, meaning that there were many ways of obtaining the pathological syndrome. There was no single parameter alteration which would consistently distinguish pathological from physiological dynamics. At higher dimensions in parameter space, we were able to use support vector machines to distinguish the two patterns in different regions of space and thereby trace multitarget routes from dystonic to physiological dynamics. These results suggest the use of in silico models for discovery of multitarget drug cocktails. PMID:27378922

  15. Potential Pharmacologic Treatments for Cystinuria and for Calcium Stones Associated with Hyperuricosuria

    SciTech Connect

    Goldfarb, David S.

    2012-03-14

    Two new potential pharmacologic therapies for recurrent stone disease are described. The role of hyperuricosuria in promoting calcium stones is controversial with only some but not all epidemiologic studies demonstrating associations between increasing urinary uric acid excretion and calcium stone disease. The relationship is supported by the ability of uric acid to 'salt out' (or reduce the solubility of) calcium oxalate in vitro. A randomized, controlled trial of allopurinol in patients with hyperuricosuria and normocalciuria was also effective in preventing recurrent stones. Febuxostat, a nonpurine inhibitor of xanthine oxidase (also known as xanthine dehydrogenase or xanthine oxidoreductase) may have advantages over allopurinol and is being tested in a similar protocol, with the eventual goal of determining whether urate-lowering therapy prevents recurrent calcium stones. Treatments for cystinuria have advanced little in the past 30 years. Atomic force microscopy has been used recently to demonstrate that effective inhibition of cystine crystal growth is accomplished at low concentrations of L-cystine methyl ester and L-cystine dimethyl ester, structural analogs of cystine that provide steric inhibition of crystal growth. In vitro, L-cystine dimethyl ester had a significant inhibitory effect on crystal growth. The drug's safety and effectiveness will be tested in an Slc3a1 knockout mouse that serves as an animal model of cystinuria.

  16. Pharmacological Chaperone Therapy: Preclinical Development, Clinical Translation, and Prospects for the Treatment of Lysosomal Storage Disorders

    PubMed Central

    Parenti, Giancarlo; Andria, Generoso; Valenzano, Kenneth J

    2015-01-01

    Lysosomal storage disorders (LSDs) are a group of inborn metabolic diseases caused by mutations in genes that encode proteins involved in different lysosomal functions, in most instances acidic hydrolases. Different therapeutic approaches have been developed to treat these disorders. Pharmacological chaperone therapy (PCT) is an emerging approach based on small-molecule ligands that selectively bind and stabilize mutant enzymes, increase their cellular levels, and improve lysosomal trafficking and activity. Compared to other approaches, PCT shows advantages, particularly in terms of oral administration, broad biodistribution, and positive impact on patients' quality of life. After preclinical in vitro and in vivo studies, PCT is now being translated in the first clinical trials, either as monotherapy or in combination with enzyme replacement therapy, for some of the most prevalent LSDs. For some LSDs, the results of the first clinical trials are encouraging and warrant further development. Future research in the field of PCT will be directed toward the identification of novel chaperones, including new allosteric drugs, and the exploitation of synergies between chaperone treatment and other therapeutic approaches. PMID:25881001

  17. Current Pharmacological Treatment for Male LUTS due to BPH: Dutasteride or Finasteride?

    PubMed

    Pirozzi, Luisella; Sountoulides, Petros; Castellan, Pietro; Presicce, Fabrizio; Lombardo, Riccardo; Romero, Marilena; De Nunzio, Cosimo; Tubaro, Andrea; Schips, Luigi; Cindolo, Luca

    2015-01-01

    Benign prostatic hyperplasia (BPH) is a potentially progressive disease which is commonly associated with bothersome lower urinary tract symptoms (LUTS) and might result in complications, such as acute urinary retention and BPH-related surgery. In the current medical therapy scenario for LUTS attributed to BPH, only one class of drugs, 5-α reductase inhibitors (5ARIs), has been found to be effective in reducing the risk of disease progression. The two 5ARIs that are currently available include finasteride and dutasteride. These two drugs have different pharmacokinetic and pharmacodynamic properties. Greater suppression of dehydrotestosterone is achieved by dutasteride (>90% dutasteride vs 70% finasteride) which theoretically should correlate with greater efficacy in alleviating urinary symptoms. Unfortunately, this hypothesis has not yet been clinically demonstrated. The pertinent literature is scarce and heterogeneous and produces low scientific levels of evidence. The present review article aims to evaluate the comparative head-to-head studies in order to evaluate if the hypothetical clinical differences between dutasteride and finasteride do exist. Pharmacological treatment with either drug results in similar symptom improvements; however dutasteride seems to have a better profile in reducing the risk of prostate surgery and acute urinary retention (AUR). More studies are necessary to better evaluate both the clinical and pharmacoeconomic profile of the two 5ARIs. PMID:25981606

  18. Ranitidine compared to cimetidine in multiagent pharmacological treatment of porcine Pseudomonas ARDS.

    PubMed

    Byrne, K; Sielaff, T D; Carey, P D; Tatum, J L; Blocher, C R; Vasquez, A; Hirsh, J I; Sugerman, H J

    1990-02-01

    The effects of two pharmacologically distinct histamine H2 receptor antagonists were studied in combination with ibuprofen (I) and diphenhydramine (D) in a porcine model of septic ARDS. Cimetidine (C) is reported as having direct oxygen radical scavenging abilities and is an inhibitor of cytochrome P-450, whereas ranitidine (R) acts solely by H2 receptor blockade. Four groups were studied: Group Ps (n = 8) received a continuous infusion of live Pseudomonas aeruginosa 5 x 10(8) CFU/ml at 0.3 ml/20kg/min, Group C (n = 6) received a control saline infusion, and the treatment groups received I (12.5 mg/kg) and D (10 mg/kg) in combination with either C (150 mg, CID, n = 6) or R (25 mg, RID, n = 5) given at 20 and 120 minutes after the onset of Ps. Pulmonary (PAP) and systemic (SAP) arterial pressures, cardiac index (CI), PaO2, thermal cardiogreen extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux (slope index, SI) were measured. Ps infusion produced significant (p less than 0.05) cardiovascular collapse, hypoxemia and increased EVLW and SI. Both CID and RID temporarily reversed pulmonary arterial hypertension and maintained PaO2, EVLW, SAP and CI at control levels throughout the study, and significantly improved SI at 180 min. These results suggest that cimetidine and ranitidine act in this combination therapy primarily as H2 receptor antagonists. PMID:2311202

  19. New pharmacological strategies for treatment of Alzheimer's disease: focus on disease modifying drugs

    PubMed Central

    Salomone, Salvatore; Caraci, Filippo; Leggio, Gian Marco; Fedotova, Julia; Drago, Filippo

    2012-01-01

    Current approved drug treatments for Alzheimer disease (AD) include cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist memantine. These drugs provide symptomatic relief but poorly affect the progression of the disease. Drug discovery has been directed, in the last 10 years, to develop ‘disease modifying drugs’ hopefully able to counteract the progression of AD. Because in a chronic, slow progressing pathological process, such as AD, an early start of treatment enhances the chance of success, it is crucial to have biomarkers for early detection of AD-related brain dysfunction, usable before clinical onset. Reliable early biomarkers need therefore to be prospectively tested for predictive accuracy, with specific cut off values validated in clinical practice. Disease modifying drugs developed so far include drugs to reduce β amyloid (Aβ) production, drugs to prevent Aβ aggregation, drugs to promote Aβ clearance, drugs targeting tau phosphorylation and assembly and other approaches. Unfortunately none of these drugs has demonstrated efficacy in phase 3 studies. The failure of clinical trials with disease modifying drugs raises a number of questions, spanning from methodological flaws to fundamental understanding of AD pathophysiology and biology. Recently, new diagnostic criteria applicable to presymptomatic stages of AD have been published. These new criteria may impact on drug development, such that future trials on disease modifying drugs will include populations susceptible to AD, before clinical onset. Specific problems with completed trials and hopes with ongoing trials are discussed in this review. PMID:22035455

  20. [Non pharmacological treatment for Alzheimer's disease: comparison between musical and non-musical interventions].

    PubMed

    Narme, Pauline; Tonini, Audrey; Khatir, Fatiha; Schiaratura, Loris; Clément, Sylvain; Samson, Séverine

    2012-06-01

    On account of the limited effectiveness of pharmacological treatments in Alzheimer's disease (AD), there is a growing interest on nonpharmacological treatments, including musical intervention. Despite the large number of studies showing the multiple benefits of music on behavioral, emotional and cognitive disorders of patients with AD, only a few of them used a rigorous method. Finally, the specificity of musical as compared to non-musical and pleasant interventions has rarely been addressed. To investigate this issue, two randomized controlled trials were conducted contrasting the effects of musical to painting (Study 1) or cooking (Study 2) interventions on emotional state of 33 patients with AD. The patients' emotional state was assessed by analyzing professional caregivers' judgments of the patient's mood, then facial expressions and valence of the discourse from short-filmed interviews. In the first study (n=22), each intervention lasted 3 weeks (two sessions per week) and the patients' emotional state was assessed before, during and after intervention periods. After the interventions, the results showed that facial expression, discourse content and mood assessment improved (more positive than negative expressions) as compared to pre-intervention assessment. However, musical intervention was more effective and had longer effects as compared with painting. In the second study (n=11), we further examined long lasting effects of music as compared to cooking by adding evaluation of the patients' emotional state 2 and 4 weeks after the last intervention. Again, music was more effective to improve the emotional state. Music had positive effects that remained significant up to 4 weeks after the intervention, while cooking only produced short-term effect on mood. In both studies, benefits were significant in more than 80% of patients. Taken together, these findings show that music intervention has specific effects on patients' emotional well being, offering promising

  1. Optimizing the Pharmacologic Treatment of Insomnia: Current Status and Future Horizons

    PubMed Central

    Minkel, Jared; Krystal, Andrew D.

    2013-01-01

    A number of medications are available for treating patients with insomnia. These medications include agents approved as insomnia therapies by the U.S. Food and Drug Administration (FDA), agents approved by the FDA for another condition that are used “off-label” to treat insomnia, and agents available “over-the-counter” that are taken by individuals with insomnia. These agents differ in their properties, their safety and efficacy when used for different insomnia patient subtypes, and the available data on their efficacy and safety in these subtypes. As a result, optimizing the medication treatment of insomnia for a given patient requires that the clinician select an agent for use which has characteristics that make it most likely to effectively and safely address the type of sleep difficulty experienced by that individual. This article is intended to assist clinicians and researchers in carrying out this optimization. It begins by reviewing the basic characteristics of the medications used to treat insomnia. This is followed by a review of the fundamental ways that individuals with insomnia may differ and affect the choice of medication therapy. This review includes discussions that illustrate how to best choose a medication based on the characteristics of the available medications, the key differences among insomnia patients, and the available research literature. Lastly, we discuss future directions for the optimizing pharmacologic management of insomnia. It is hoped that the treatment tailoring methods discussed herein serve as a means of improving the clinical management of insomnia and, thus, improve the lives of the many patients who suffer from this common and impairing condition. PMID:24015116

  2. Regenerative pharmacology in the treatment of genetic diseases: The paradigm of muscular dystrophy

    PubMed Central

    Mozzetta, Chiara; Minetti, Giulia; Puri, Pier Lorenzo

    2009-01-01

    Current evidence supports the therapeutic potential of pharmacological interventions that counter the progression of genetic disorders by promoting regeneration of the affected organs or tissues. The rationale behind this concept lies on the evidence that targeting key events downstream of the genetic defect can compensate, at least partially, the pathological consequence of the related disease. In this regard, the beneficial effect exerted on animal models of muscular dystrophy by pharmacological strategies that enhance muscle regeneration provides an interesting paradigm. In this review, we describe and discuss the potential targets of pharmacological strategies that promote regeneration of dystrophic muscles and alleviate the consequence of the primary genetic defect. Regenerative pharmacology provides an immediate and suitable therapeutic opportunity to slow down the decline of muscles in the present generation of dystrophic patients, with the perspective to hold them in conditions such that they could benefit of future, more definitive, therapies. PMID:18804548

  3. Pharmacologic Evidence to Support Clinical Decision Making for Peripartum Methadone Treatment

    PubMed Central

    Bogen, D. L.; Perel, J. M.; Helsel, J. C.; Hanusa, B. H.; Romkes, M.; Nukui, T.; Friedman, C. R.; Wisner, K. L.

    2012-01-01

    Rationale Limited pharmacological data are available to guide methadone treatment during pregnancy and postpartum. Objectives Study goals were to: 1) Characterize changes in methadone dose across childbearing, 2) Determine enantiomer-specific methadone withdrawal kinetics from steady-state during late pregnancy, 3) Assess enantiomer-specific changes in methadone level/dose (L/D) ratios across childbearing, and 4) Explore relationships between CYP2B6, CYP2C19 and CYP3A4 single nucleotide polymorphisms and maternal dose, plasma concentration and L/D. Methods Methadone dose changes and timed plasma samples were obtained for women on methadone (n=25) followed prospectively from third trimester of pregnancy to three months postpartum. Results Participants were primarily white, Medicaid insured and multiparous. All women increased their dose from first to end of second trimester (mean peak increase=23 mg/day); 71% of women increased from second trimester to delivery (mean peak increase=19 mg/day). Half took a higher dose 3 months postpartum than at delivery despite significantly larger clearance during late pregnancy. Third trimester enantiomer-specific methadone half-lives (range R-methadone 14.7-24.9 hours; S-methadone 8.02-18.9 hours) were about half of those reported in non-pregnant populations. In 3 women with weekly 24-hour methadone levels after delivery, L/D increased within 1-2 weeks after delivery. Women with the CYP2B6 Q172 variant GT genotype have consistently higher L/D values for S-methadone across both pregnancy and postpartum. Conclusions Most women require increases in methadone dose across pregnancy. Given the shorter half-life and larger clearances during pregnancy, many pregnant women may benefit from split methadone dosing. L/D increases quickly after delivery and doses should be lowered rapidly after delivery. PMID:22926004

  4. Thiopurine treatment in inflammatory bowel disease: clinical pharmacology and implication of pharmacogenetically guided dosing.

    PubMed

    Teml, Alexander; Schaeffeler, Elke; Herrlinger, Klaus R; Klotz, Ulrich; Schwab, Matthias

    2007-01-01

    This review summarises clinical pharmacological aspects of thiopurines in the treatment of chronic inflammatory bowel disease (IBD). Current knowledge of pharmacogenetically guided dosing is discussed for individualisation of thiopurine therapy, particularly to avoid severe adverse effects. Both azathioprine and mercaptopurine are pro-drugs that undergo extensive metabolism. The catabolic enzyme thiopurine S-methyltransferase (TPMT) is polymorphically expressed, and currently 23 genetic variants have been described. On the basis of an excellent phenotype-genotype correlation for TPMT, genotyping has become a safe and reliable tool for determination of a patient's individual phenotype. Thiopurine-related adverse drug reactions are frequent, ranging from 5% up to 40%, in both a dose-dependent and -independent manner. IBD patients with low TPMT activity are at high risk of developing severe haematotoxicity if pharmacogenetically guided dosing is not performed. Based on several cost-benefit analyses, assessment of TPMT activity is recommended prior to thiopurine therapy in patients with IBD. The underlying mechanisms of azathioprine/mercaptopurine-related hepatotoxicity, pancreatitis and azathioprine intolerance are still unknown. Although the therapeutic response appears to be related to 6-thioguanine nucleotide (6-TGN) concentrations above a threshold of 230-260 pmol per 8 x 10(8) red blood cells, at present therapeutic drug monitoring of 6-TGN can be recommended only to estimate patients' compliance.Drug-drug interactions between azathioprine/mercaptopurine and aminosalicylates, diuretics, NSAIDs, warfarin and infliximab are discussed. The concomitant use of allopurinol without dosage adjustment of azathioprine/mercaptopurine leads to clinically relevant severe haematotoxicity due to elevated thiopurine levels. Several studies indicate that thiopurine therapy in IBD during pregnancy is safe. Thus, azathioprine/mercaptopurine should not be withdrawn in strictly

  5. Fitting proposals to their sequential environment: a comparison of turn designs for proposing treatment in ongoing outpatient psychiatric consultations in Japan.

    PubMed

    Kushida, Shuya; Yamakawa, Yuriko

    2015-05-01

    This study is an attempt to describe an interactional strategy that psychiatrists use in making decisions for treatment in ongoing outpatient psychiatric consultations in Japan. Using conversation analysis (CA), we compare sequential environments where psychiatrists use two turn designs for proposing a treatment: the inclusive 'we' form (for example 'let's' and 'how about') and the declarative evaluation (for example, 'it might be better'). The inclusive 'we' form is used to create the moment for decision when the sequential environment is ready for decision-making. The declarative evaluation is used to propose a treatment cautiously when the sequential environment is not yet ready for decision-making. Taken together, psychiatrists fit the turn design of a proposal to its sequential environment in such a way as to display their attention to the patients' perspectives. In conclusion, we argue that our finding provides further evidence for the claim made by a growing body of CA research that, unlike the traditional sociological understanding of doctor-patient interaction, doctors do not simply impose their perspectives upon the patients but steer medical encounters to their preferred direction by orienting to the patients' perspectives. PMID:25677465

  6. The use of functional neuroimaging to evaluate psychological and other non-pharmacological treatments for clinical pain.

    PubMed

    Jensen, Karin B; Berna, Chantal; Loggia, Marco L; Wasan, Ajay D; Edwards, Robert R; Gollub, Randy L

    2012-06-29

    A large number of studies have provided evidence for the efficacy of psychological and other non-pharmacological interventions in the treatment of chronic pain. While these methods are increasingly used to treat pain, remarkably few studies focused on the exploration of their neural correlates. The aim of this article was to review the findings from neuroimaging studies that evaluated the neural response to distraction-based techniques, cognitive behavioral therapy (CBT), clinical hypnosis, mental imagery, physical therapy/exercise, biofeedback, and mirror therapy. To date, the results from studies that used neuroimaging to evaluate these methods have not been conclusive and the experimental methods have been suboptimal for assessing clinical pain. Still, several different psychological and non-pharmacological treatment modalities were associated with increased pain-related activations of executive cognitive brain regions, such as the ventral- and dorsolateral prefrontal cortex. There was also evidence for decreased pain-related activations in afferent pain regions and limbic structures. If future studies will address the technical and methodological challenges of today's experiments, neuroimaging might have the potential of segregating the neural mechanisms of different treatment interventions and elucidate predictive and mediating factors for successful treatment outcomes. Evaluations of treatment-related brain changes (functional and structural) might also allow for sub-grouping of patients and help to develop individualized treatments. PMID:22445888

  7. Inhibition of caspases prevents ototoxic and ongoing hair cell death

    NASA Technical Reports Server (NTRS)

    Matsui, Jonathan I.; Ogilvie, Judith M.; Warchol, Mark E.

    2002-01-01

    Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal transduction pathways that mediate hair cell death are not known. Here we identify several important signaling events that regulate the death of vestibular hair cells. Chick utricles were cultured in media supplemented with the ototoxic antibiotic neomycin and selected pharmacological agents that influence signaling molecules in cell death pathways. Hair cells that were treated with neomycin exhibited classically defined apoptotic morphologies such as condensed nuclei and fragmented DNA. Inhibition of protein synthesis (via treatment with cycloheximide) increased hair cell survival after treatment with neomycin, suggesting that hair cell death requires de novo protein synthesis. Finally, the inhibition of caspases promoted hair cell survival after neomycin treatment. Sensory hair cells in avian vestibular organs also undergo continual cell death and replacement throughout mature life. It is unclear whether the loss of hair cells stimulates the proliferation of supporting cells or whether the production of new cells triggers the death of hair cells. We examined the effects of caspase inhibition on spontaneous hair cell death in the chick utricle. Caspase inhibitors reduced the amount of ongoing hair cell death and ongoing supporting cell proliferation in a dose-dependent manner. In isolated sensory epithelia, however, caspase inhibitors did not affect supporting cell proliferation directly. Our data indicate that ongoing hair cell death stimulates supporting cell proliferation in the mature utricle.

  8. Cocaine: Pharmacology, Effects, and Treatment of Abuse. National Institute on Drug Abuse Research Monograph 50.

    ERIC Educational Resources Information Center

    Grabowski, John, Ed.

    This monograph consists of eight papers which refer in one way or another to the pharmacology of cocaine. The papers are: (1) Cocaine 1984: Introduction and Overview" (John Grabowski); (2) "Cocaine: A Growing Public Health Problem" (Edgar H. Adams and Jack Durell); (3) "Neural Mechanisms of the Reinforcing Action of Cocaine" (Roy A. Wise); (4)…

  9. Practitioner Review: Non-Pharmacological Treatments for ADHD: A Lifespan Approach

    ERIC Educational Resources Information Center

    Young, Susan; Amarasinghe, J. Myanthi

    2010-01-01

    Background: Attention-deficit/hyperactivity disorder (ADHD) is a chronic and pervasive developmental disorder that is not restricted to the childhood years. Methods: This paper reviews non-pharmacological interventions that are available at present for preschoolers, school-age children, adolescents and adults. Results: The most appropriate…

  10. Combination fluconazole/paroxetine treatment is neuroprotective despite ongoing neuroinflammation and viral replication in an SIV model of HIV neurological disease

    PubMed Central

    Meulendyke, Kelly A.; Queen, Suzanne E.; Engle, Elizabeth L.; Shirk, Erin N.; Liu, Jiayang; Steiner, Joseph P.; Nath, Avindra; Tarwater, Patrick M.; Graham, David R.; Mankowski, Joseph L.; Zink, M. Christine

    2014-01-01

    Effective combined antiretroviral therapy (cART) in HIV infected patients has made HIV a treatable condition; however, debilitating HIV-associated neurocognitive disorders (HAND) can still affect up to 50% of HIV infected individuals even under cART. While cART has greatly reduced the prevalence of the most severe form of HAND, milder forms have increased in prevalence, leaving a the total proportion of HIV-infected individuals suffering from HAND relatively unchanged. In this study an in vitro drug screen identified fluconazole and paroxetine as protective compounds against HIV gp120 and Tat neurotoxicity. Using an accelerated, consistent SIV/macaque model of HIV-associated CNS disease, we tested the in vivo neuroprotective capabilities of combination fluconazole/paroxetine (FluPar) treatment. FluPar treatment protected macaques from SIV-induced neurodegeneration, as measured by neurofilament light chain in the CSF, APP accumulation in the axons, and CaMKIIα in the frontal cortex, but did not significantly reduce markers of neuroinflammation or plasma or CNS viral loads. Since HIV and SIV neurodegeneration is often attributed to accompanying neuroinflammation, this study provides proof of concept that neuroprotection can be achieved even in the face of ongoing neuroinflammation and viral replication. PMID:25227932

  11. Pharmacologic treatment for urgency-predominant urinary incontinence in women diagnosed using a simplified algorithm: a randomized trial

    PubMed Central

    Huang, Alison J.; Hess, Rachel; Arya, Lily A.; Richter, Holly E.; Subak, Leslee L.; Bradley, Catherine S.; Rogers, Rebecca G.; Myers, Deborah L.; Johnson, Karen C.; Gregory, W. Thomas; Kraus, Stephen R.; Schembri, Michael; Brown, Jeanette S.

    2013-01-01

    Objective The purpose of this study was to evaluate clinical outcomes associated with the initiation of treatment for urgency-predominant incontinence in women diagnosed by a simple 3-item questionnaire. Study Design We conducted a multicenter, double-blinded, 12-week randomized trial of pharmacologic therapy for urgency-predominant incontinence in ambulatory women diagnosed by the simple 3-item questionnaire. Participants (N = 645) were assigned randomly to fesoterodine therapy (4-8 mg daily) or placebo. Urinary incontinence was assessed with the use of voiding diaries; postvoid residual volume was measured after treatment. Results After 12 weeks, women who had been assigned randomly to fesoterodine therapy reported 0.9 fewer urgency and 1.0 fewer total incontinence episodes/day, compared with placebo (P ≤ .001). Four serious adverse events occurred in each group, none of which was related to treatment. No participant had postvoid residual volume of ≥250 mL after treatment. Conclusion Among ambulatory women with urgency-predominant incontinence diagnosed with a simple 3-item questionnaire, pharmacologic therapy resulted in a moderate decrease in incontinence frequency without increasing significant urinary retention or serious adverse events, which provides support for a streamlined algorithm for diagnosis and treatment of female urgency-predominant incontinence. PMID:22542122

  12. Fish Oil–Based Lipid Emulsions in the Treatment of Parenteral Nutrition-Associated Liver Disease: An Ongoing Positive Experience123

    PubMed Central

    Premkumar, Muralidhar H.; Carter, Beth A.; Hawthorne, Keli M.; King, Kristi; Abrams, Steven A.

    2014-01-01

    We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutrition-associated liver disease (PNALD). In this report, we share our ongoing experience at Texas Children’s Hospital, Houston, Texas in the use of FOLE in treatment of PNALD as presented at the 2013 Experimental Biology meeting. We describe the findings of a single center, prospective, observational study of infants <6 mo of age with PNALD who received parenteral FOLE as monotherapy. A total of 97 infants received FOLE under the compassionate-use protocol for the treatment of PNALD. Eighty-three (86%) survived with resolution of cholestasis and 14 (14%) died. The median conjugated bilirubin (CB) concentration at the initiation of FOLE therapy was 4.8 mg/dL (range 2.1–26). The median time to resolution of cholestasis was 40 d (range 3–158). Compared with infants with mild cholestasis (CB of 2.1–5 mg/dL at the initiation of FOLE), nonsurvivors were significantly more premature and took longer to resolve their cholestasis. Gestational age at birth correlated inversely with CB at the beginning of FOLE and peak CB. Infants with an initial CB >10 mg/dL had a higher mortality rate than infants with an initial CB <5 mg/dL (35% vs. 6%; P < 0.05). Our experience with the use of FOLE in PNALD continues to be encouraging. Prematurity continues to be a major determinant in mortality and severity of cholestasis. This calls for further controlled studies designed to optimize dose and timing of intervention in the use of FOLE in neonates. PMID:24425724

  13. Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM

    PubMed Central

    Wang, Yonghua; Zheng, Chunli; Huang, Chao; Li, Yan; Chen, Xuetong; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Zhang, Boli

    2015-01-01

    Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc.) to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs) by TCM (traditional Chinese medicine). Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future. PMID:26101539

  14. Developments in harmine pharmacology--implications for ayahuasca use and drug-dependence treatment.

    PubMed

    Brierley, Daniel I; Davidson, Colin

    2012-12-01

    Ayahuasca is a hallucinogenic botanical mixture originating in the Amazon area where it is used ritually, but is now being taken globally. The 2 main constituents of ayahuasca are N,N-dimethyltryptamine (DMT), a hallucinogen, and harmine, a monoamine oxidase inhibitor (MAOI) which attenuates the breakdown of DMT, which would otherwise be broken down very quickly after oral consumption. Recent developments in ayahuasca use include the sale of these compounds on the internet and the substitution of related botanical (anahuasca) or synthetic (pharmahuasca) compounds to achieve the same desired hallucinogenic effects. One intriguing result of ayahuasca use appears to be improved mental health and a reduction in recidivism to alternate (alcohol, cocaine) drug use. In this review we discuss the pharmacology of ayahuasca, with a focus on harmine, and suggest pharmacological mechanisms for the putative reduction in recidivism to alcohol and cocaine misuse. These pharmacological mechanisms include MAOI, effects at 5-HT(2A) and imidazoline receptors and inhibition of dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) and the dopamine transporter. We also speculate on the therapeutic potential of harmine in other CNS conditions. PMID:22691716

  15. Pharmacological treatment of idiopathic pulmonary fibrosis – preclinical and clinical studies of pirfenidone, nintedanib, and N-acetylcysteine

    PubMed Central

    Myllärniemi, Marjukka; Kaarteenaho, Riitta

    2015-01-01

    Three recent clinical trials on the pharmacologic treatment of idiopathic pulmonary fibrosis (IPF) mark a new chapter in the management of patients suffering from this very severe fibrotic lung disease. This review article summarizes the published investigations on the preclinical studies of three novel IPF drugs, namely pirfenidone, nintedanib, and N-acetylcysteine (NAC). In addition, the study protocols, differences, and the main findings in the recent clinical trials of these pharmacological treatments are reviewed. The strategy for drug development and the timeline from the discovery to the clinical use have been very different in these regimens. Pirfenidone was discovered in 1976 but only recently received approval in most countries, and even now its exact mechanism of action is unknown. On the contrary, nintedanib (BIBF1120) was identified in large drug screening tests as a very specific inhibitor of certain tyrosine kinases, but no published data on preclinical tests existed until 2014. NAC, a mucolytic drug with an antioxidant mechanism of action was claimed to possess distinct antifibrotic properties in several experimental models but proved to be ineffective in a recent randomized placebo-controlled trial. At present, no curative treatment is available for IPF. A better understanding of the molecular mechanisms of IPF as well as relevant preclinical tests including animal models and in vitro experiments on human lung cells are needed to promote the development of therapeutic drugs. PMID:26557253

  16. Advances in the pharmacological treatment of Parkinson's disease: targeting neurotransmitter systems.

    PubMed

    Brichta, Lars; Greengard, Paul; Flajolet, Marc

    2013-09-01

    For several decades, the dopamine precursor levodopa has been the primary therapy for Parkinson's disease (PD). However, not all of the motor and non-motor features of PD can be attributed solely to dopaminergic dysfunction. Recent clinical and preclinical advances provide a basis for the identification of additional innovative therapeutic options to improve the management of the disease. Novel pharmacological strategies must be optimized for PD by: (i) targeting disturbances of the serotonergic, noradrenergic, glutamatergic, GABAergic, and cholinergic systems in addition to the dopaminergic system, and (ii) characterizing alterations in the levels of neurotransmitter receptors and transporters that are associated with the various manifestations of the disease. PMID:23876424

  17. Systems Pharmacology Uncovers the Multiple Mechanisms of Xijiao Dihuang Decoction for the Treatment of Viral Hemorrhagic Fever

    PubMed Central

    Liu, Jianling; Pei, Tianli; Mu, Jiexin; Zheng, Chunli; Chen, Xuetong; Huang, Chao; Fu, Yingxue; Liang, Zongsuo; Wang, Yonghua

    2016-01-01

    Background. Viral hemorrhagic fevers (VHF) are a group of systemic diseases characterized by fever and bleeding, which have posed a formidable potential threat to public health with high morbidity and mortality. Traditional Chinese Medicine (TCM) formulas have been acknowledged with striking effects in treatment of hemorrhagic fever syndromes in China's history. Nevertheless, their accurate mechanisms of action are still confusing. Objective. To systematically dissect the mechanisms of action of Chinese medicinal formula Xijiao Dihuang (XJDH) decoction as an effective treatment for VHF. Methods. In this study, a systems pharmacology method integrating absorption, distribution, metabolism, and excretion (ADME) screening, drug targeting, network, and pathway analysis was developed. Results. 23 active compounds of XJDH were obtained and 118 VHF-related targets were identified to have interactions with them. Moreover, systematic analysis of drug-target network and the integrated VHF pathway indicate that XJDH probably acts through multiple mechanisms to benefit VHF patients, which can be classified as boosting immune system, restraining inflammatory responses, repairing the vascular system, and blocking virus spread. Conclusions. The integrated systems pharmacology method provides precise probe to illuminate the molecular mechanisms of XJDH for VHF, which will also facilitate the application of traditional medicine in modern medicine. PMID:27239215

  18. Systems-Pharmacology Dissection of Traditional Chinese Medicine Compound Saffron Formula Reveals Multi-scale Treatment Strategy for Cardiovascular Diseases.

    PubMed

    Liu, Jianling; Mu, Jiexin; Zheng, Chunli; Chen, Xuetong; Guo, Zihu; Huang, Chao; Fu, Yingxue; Tian, Guihua; Shang, Hongcai; Wang, Yonghua

    2016-01-01

    Cardiovascular diseases (CVDs) have been regarding as "the world's first killer" of human beings in recent years owing to the striking morbidity and mortality, the involved molecular mechanisms are extremely complex and remain unclear. Traditional Chinese medicine (TCM) adheres to the aim of combating complex diseases from an integrative and holistic point of view, which has shown effectiveness in CVDs therapy. However, system-level understanding of such a mechanism of multi-scale treatment strategy for CVDs is still difficult. Here, we developed a system pharmacology approach with the purpose of revealing the underlying molecular mechanisms exemplified by a famous compound saffron formula (CSF) in treating CVDs. First, by systems ADME analysis combined with drug targeting process, 103 potential active components and their corresponding 219 direct targets were retrieved and some key interactions were further experimentally validated. Based on this, the network relationships among active components, targets and diseases were further built to uncover the pharmacological actions of the drug. Finally, a "CVDs pathway" consisted of several regulatory modules was incorporated to dissect the therapeutic effects of CSF in different pathological features-relevant biological processes. All this demonstrates CSF has multi-scale curative activity in regulating CVD-related biological processes, which provides a new potential way for modern medicine in the treatment of complex diseases. PMID:26813334

  19. Systems pharmacology dissection of multi-scale mechanisms of action for herbal medicines in stroke treatment and prevention.

    PubMed

    Zhang, Jingxiao; Li, Yan; Chen, Xuetong; Pan, Yanqiu; Zhang, Shuwei; Wang, Yonghua

    2014-01-01

    Annually, tens of millions of first-ever strokes occur in the world; however, currently there is lack of effective and widely applicable pharmacological treatments for stroke patients. Herbal medicines, characterized as multi-constituent, multi-target and multi-effect, have been acknowledged with conspicuous effects in treating stroke, and attract extensive interest of researchers although the mechanism of action is yet unclear. In this work, we introduce an innovative systems-pharmacology method that combines pharmacokinetic prescreening, target fishing and network analysis to decipher the mechanisms of action of 10 herbal medicines like Salvia miltiorrhizae, Ginkgo biloba and Ephedrae herba which are efficient in stroke treatment and prevention. Our systematic analysis results display that, in these anti-stroke herbal medicines, 168 out of 1285 constituents with the favorable pharmacokinetic profiles might be implicated in stroke therapy, and the systematic use of these compounds probably acts through multiple mechanisms to synergistically benefit patients with stroke, which can roughly be classified as preventing ischemic inflammatory response, scavenging free radicals and inhibiting neuronal apoptosis against ischemic cerebral damage, as well as exhibiting lipid-lowering, anti-diabetic, anti-thrombotic and antiplatelet effects to decrease recurrent strokes. Relying on systems biology-based analysis, we speculate that herbal medicines, being characterized as the classical combination therapies, might be not only engaged in multiple mechanisms of action to synergistically improve the stroke outcomes, but also might be participated in reducing the risk factors for recurrent strokes. PMID:25093322

  20. African herbal medicines in the treatment of HIV: Hypoxis and Sutherlandia. An overview of evidence and pharmacology

    PubMed Central

    Mills, Edward; Cooper, Curtis; Seely, Dugald; Kanfer, Izzy

    2005-01-01

    In Africa, herbal medicines are often used as primary treatment for HIV/AIDS and for HIV-related problems. In general, traditional medicines are not well researched, and are poorly regulated. We review the evidence and safety concerns related to the use of two specific African herbals, which are currently recommended by the Ministry of Health in South Africa and member states for use in HIV: African Potato and Sutherlandia. We review the pharmacology, toxicology and pharmacokinetics of these herbal medicines. Despite the popularity of their use and the support of Ministries of Health and NGOs in some African countries, no clinical trials of efficacy exist, and low-level evidence of harm identifies the potential for drug interactions with antiretroviral drugs. Efforts should be made by mainstream health professionals to provide validated information to traditional healers and patients on the judicious use of herbal remedies. This may reduce harm through failed expectations, pharmacologic adverse events including possible drug/herb interactions and unnecessary added therapeutic costs. Efforts should also be directed at evaluating the possible benefits of natural products in HIV/AIDS treatment. PMID:15927053

  1. Systems Pharmacology Uncovers the Multiple Mechanisms of Xijiao Dihuang Decoction for the Treatment of Viral Hemorrhagic Fever.

    PubMed

    Liu, Jianling; Pei, Tianli; Mu, Jiexin; Zheng, Chunli; Chen, Xuetong; Huang, Chao; Fu, Yingxue; Liang, Zongsuo; Wang, Yonghua

    2016-01-01

    Background. Viral hemorrhagic fevers (VHF) are a group of systemic diseases characterized by fever and bleeding, which have posed a formidable potential threat to public health with high morbidity and mortality. Traditional Chinese Medicine (TCM) formulas have been acknowledged with striking effects in treatment of hemorrhagic fever syndromes in China's history. Nevertheless, their accurate mechanisms of action are still confusing. Objective. To systematically dissect the mechanisms of action of Chinese medicinal formula Xijiao Dihuang (XJDH) decoction as an effective treatment for VHF. Methods. In this study, a systems pharmacology method integrating absorption, distribution, metabolism, and excretion (ADME) screening, drug targeting, network, and pathway analysis was developed. Results. 23 active compounds of XJDH were obtained and 118 VHF-related targets were identified to have interactions with them. Moreover, systematic analysis of drug-target network and the integrated VHF pathway indicate that XJDH probably acts through multiple mechanisms to benefit VHF patients, which can be classified as boosting immune system, restraining inflammatory responses, repairing the vascular system, and blocking virus spread. Conclusions. The integrated systems pharmacology method provides precise probe to illuminate the molecular mechanisms of XJDH for VHF, which will also facilitate the application of traditional medicine in modern medicine. PMID:27239215

  2. Systems-Pharmacology Dissection of Traditional Chinese Medicine Compound Saffron Formula Reveals Multi-scale Treatment Strategy for Cardiovascular Diseases

    PubMed Central

    Liu, Jianling; Mu, Jiexin; Zheng, Chunli; Chen, Xuetong; Guo, Zihu; Huang, Chao; Fu, Yingxue; Tian, Guihua; Shang, Hongcai; Wang, Yonghua

    2016-01-01

    Cardiovascular diseases (CVDs) have been regarding as “the world’s first killer” of human beings in recent years owing to the striking morbidity and mortality, the involved molecular mechanisms are extremely complex and remain unclear. Traditional Chinese medicine (TCM) adheres to the aim of combating complex diseases from an integrative and holistic point of view, which has shown effectiveness in CVDs therapy. However, system-level understanding of such a mechanism of multi-scale treatment strategy for CVDs is still difficult. Here, we developed a system pharmacology approach with the purpose of revealing the underlying molecular mechanisms exemplified by a famous compound saffron formula (CSF) in treating CVDs. First, by systems ADME analysis combined with drug targeting process, 103 potential active components and their corresponding 219 direct targets were retrieved and some key interactions were further experimentally validated. Based on this, the network relationships among active components, targets and diseases were further built to uncover the pharmacological actions of the drug. Finally, a “CVDs pathway” consisted of several regulatory modules was incorporated to dissect the therapeutic effects of CSF in different pathological features-relevant biological processes. All this demonstrates CSF has multi-scale curative activity in regulating CVD-related biological processes, which provides a new potential way for modern medicine in the treatment of complex diseases. PMID:26813334

  3. Ongoing Space Nuclear Activities

    NASA Technical Reports Server (NTRS)

    Houts, Michael G.

    2007-01-01

    Most ongoing US activities related to space nuclear power and propulsion are sponsored by NASA. NASA-spons0red space nuclear work is currently focused on evaluating potential fission surface power (FSP) systems and on radioisotope power systems (RPS). In addition, significant efforts related to nuclear thermal propulsion (NTP) systems have been completed and will provide a starting point for potential future NTP work.

  4. Pharmacology and clinical potential of guanylyl cyclase C agonists in the treatment of ulcerative colitis

    PubMed Central

    Pitari, Giovanni M

    2013-01-01

    Agonists of the transmembrane intestinal receptor guanylyl cyclase C (GCC) have recently attracted interest as promising human therapeutics. Peptide ligands that can specifically induce GCC signaling in the intestine include endogenous hormones guanylin and uroguanylin, diarrheagenic bacterial enterotoxins (ST), and synthetic drugs linaclotide, plecanatide, and SP-333. These agonists bind to GCC at intestinal epithelial surfaces and activate the receptor’s intracellular catalytic domain, an event initiating discrete biological responses upon conversion of guanosine-5′-triphosphate to cyclic guanosine monophosphate. A principal action of GCC agonists in the colon is the promotion of mucosal homeostasis and its dependent barrier function. Herein, GCC agonists are being developed as new medications to treat inflammatory bowel diseases, pathological conditions characterized by mucosal barrier hyperpermeability, abnormal immune reactions, and chronic local inflammation. This review will present important concepts underlying the pharmacology and therapeutic utility of GCC agonists for patients with ulcerative colitis, one of the most prevalent inflammatory bowel disease disorders. PMID:23637522

  5. Dolutegravir – a review of the pharmacology, efficacy, and safety in the treatment of HIV

    PubMed Central

    Kandel, Christopher E; Walmsley, Sharon L

    2015-01-01

    Dolutegravir is the newest integrase strand transfer inhibitor to be approved for the treatment of human immunodeficiency virus (HIV) infection. Dolutegravir is equivalent or superior to existing treatment regimens in both treatment-naïve and treatment-experienced patients including those with previous raltegravir or elvitegravir failure. The consistent efficacy coupled with excellent tolerability and infrequent drug–drug interactions makes the co-formulation of dolutegravir with two nucleotide reverse-transcriptase inhibitors an attractive treatment option. This review summarizes the pharmacokinetics, adverse event profile, and efficacy of dolutegravir in the treatment of HIV. PMID:26185421

  6. Ongoing Pharmacological Management of Chronic Pain in Pregnancy.

    PubMed

    Källén, Bengt; Reis, Margareta

    2016-06-01

    The article discusses possible effects of the use of analgesics during pregnancy. It summarizes the pertinent literature and reports some previously unpublished data from the Swedish Medical Birth Register. Most likely the use of analgesics does not cause spontaneous abortion. Only small malformation risk increases are seen after the use of opioids and perhaps non-steroid anti-inflammatory drug (NSAID) use. If possible, the latter should be avoided during the first trimester. If exposure has occurred there is no reason to consider an interruption of the pregnancy. Continued use of analgesics may increase the risk of preeclampsia and of preterm birth, especially valid for opioids. Use of acetylsalicylic acid (ASA) in late pregnancy should be avoided because of the risk of bleeding and (valid also for NSAIDs) premature closure of the ductus arteriosus. A small risk for neonatal abstinence syndrome may exist after the use of opioids for chronic pain, notably during the third trimester and long-lasting effects on child development can possibly occur. For a woman with chronic pain, adequate use of pain killers during pregnancy is needed. It is prudent to avoid ASA and NSAIDs towards the end of the pregnancy, while acetaminophen is an acceptable option all through pregnancy. If continued use of opioids is necessary, the associated risks are low. Triptans can be used for migraine during pregnancy. If possible sumatriptan is preferable to other triptans as data for the latter are largely lacking. Ergots are preferably avoided as not enough data are available. PMID:27154242

  7. Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

    PubMed

    Huard, J; Mu, X; Lu, A

    2016-08-01

    Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease. PMID:27071500

  8. Ongoing Clinical Trials for Vasovagal Syncope: Where are we in 2014?

    PubMed Central

    Coffin, Samuel T; Raj, Satish R

    2014-01-01

    Vasovagal Syncope (VVS) can lead to a markedly diminished quality of life for some patients. While there are many treatments for this condition including physical, mechanical, pharmacologic, and device-based control of heart rate, there are few that have been shown to be effective in randomized clinical trials. In our local experience, we have achieved significant improvement in symptom frequency and quality of life using algorithms based on the data available and on clinical acumen for the majority of patients with VVS. Despite this, there are still many patients who suffer from treatment refractory VVS. Fortunately, there are a number of ongoing clinical trials that are likely to add to our knowledge. Ongoing clinical trials are reviewed to examine new treatment methods for VVS that were listed on public trial registries as of April 15, 2014. Data from these trials should inform future strategies in the care of patients with VVS. PMID:24913692

  9. A novel Werner Syndrome mutation: pharmacological treatment by read-through of nonsense mutations and epigenetic therapies

    PubMed Central

    Agrelo, Ruben; Sutz, Miguel Arocena; Setien, Fernando; Aldunate, Fabian; Esteller, Manel; Da Costa, Valeria; Achenbach, Ricardo

    2015-01-01

    Werner Syndrome (WS) is a rare inherited disease characterized by premature aging and increased propensity for cancer. Mutations in the WRN gene can be of several types, including nonsense mutations, leading to a truncated protein form. WRN is a RecQ family member with both helicase and exonuclease activities, and it participates in several cell metabolic pathways, including DNA replication, DNA repair, and telomere maintenance. Here, we reported a novel homozygous WS mutation (c.3767 C > G) in 2 Argentinian brothers, which resulted in a stop codon and a truncated protein (p.S1256X). We also observed increased WRN promoter methylation in the cells of patients and decreased messenger WRN RNA (WRN mRNA) expression. Finally, we showed that the read-through of nonsense mutation pharmacologic treatment with both aminoglycosides (AGs) and ataluren (PTC-124) in these cells restores full-length protein expression and WRN functionality. PMID:25830902

  10. MP29-02 for the treatment of seasonal allergic rhinitis: a review of clinical pharmacology, efficacy and safety.

    PubMed

    Berger, William E

    2013-09-01

    This review presents the pharmacology, clinical efficacy and safety of MP29-02 (Dymista®), a unique product for the treatment of allergic rhinitis. Allergic rhinitis is often thought of more as a nuisance than a meaningful medical condition, and the health impact of allergic rhinitis can easily be underestimated. As a result, allergic rhinitis can be undertreated, expectations for relief may not be met, and patients may be left dissatisfied and non-compliant with their medications. MP29-02 is the only currently available allergic rhinitis medication to provide potent early-phase histamine-receptor blocking and long-term anti-inflammatory effects in a single intranasal formulation and delivery system that represents an advance in the therapy of allergic rhinitis, in particular for patients with moderate-to-severe disease. PMID:24070043

  11. Pharmacological Treatment of Post-Prostatectomy Incontinence: What is the Evidence?

    PubMed

    Løvvik, Anja; Müller, Stig; Patel, Hitendra R H

    2016-08-01

    Urinary incontinence is a common and debilitating problem, and post-prostatectomy incontinence (PPI) is becoming an increasing problem, with a higher risk among elderly men. Current treatment options for PPI include pelvic floor muscle exercises and surgery. Conservative treatment has disputable effects, and surgical treatment is expensive, is not always effective, and may have complications. This article describes the prevalence and causes of PPI and the current treatment methods. We conducted a search of the PUBMED database and reviewed the current literature on novel medical treatments of PPI, with special focus on the aging man. Antimuscarinic drugs, phosphodiesterase inhibitors, duloxetine, and α-adrenergic drugs have been proposed as medical treatments for PPI. Most studies were small and used different criteria for quantifying incontinence and assessing treatment results. Thus, there is not enough evidence to recommend the use of these medications as standard treatment of PPI. To determine whether medical therapy is a viable option in the treatment of PPI, randomized, placebo-controlled studies are needed that also assess side effects in the elderly population. PMID:27554370

  12. Non-pharmacological treatments in autism spectrum disorders: an overview on early interventions for pre-schoolers.

    PubMed

    Narzisi, Antonio; Costanza, Colombi; Umberto, Balottin; Filippo, Muratori

    2014-02-01

    This paper evaluates the current literature on non-pharmacological early interventions (behavior behavioral, developmental and educational approaches) for pre-schoolers (aged 24-71 months) with autism spectrum disorders. Although there lies a significant heterogeneity among the available studies, the present review emphasizes the importance of considering the wide range of interventions through behavioral (behavioral or developmental interventions) and educational continuum according to the suggestions of the recent literature in this field. Furthermore, the present review: 1) outlines the issues about the scientific validity of the treatment outcome studies; 2) describes the findings of different parent-mediated interventions; 3) highlights the importance to use the same outcome measures through the studies to compare findings of different literature contributions; and 4) focuses on the importance to consider pre-treatment variables to identify children who will have better outcomes. Furthermore, some evidence-based guidelines about clinical management and treatment have also been outlined and summarized in this review. Finally, the review concludes on providing a number of practical recommendations to clinicians working in the field suggesting both the presence of a specialized team and role of an active collaboration of the family to treatment as core milestones for the clinical management. PMID:24050743

  13. Pharmacological Targeting SHP-1-STAT3 Signaling Is a Promising Therapeutic Approach for the Treatment of Colorectal Cancer.

    PubMed

    Fan, Li-Ching; Teng, Hao-Wei; Shiau, Chung-Wai; Tai, Wei-Tien; Hung, Man-Hsin; Yang, Shung-Haur; Jiang, Jeng-Kai; Chen, Kuen-Feng

    2015-09-01

    STAT3 activation is associated with poor prognosis in human colorectal cancer (CRC). Our previous data demonstrated that regorafenib (Stivarga) is a pharmacological agonist of SH2 domain-containing phosphatase 1 (SHP-1) that enhances SHP-1 activity and induces apoptosis by targeting STAT3 signals in CRC. This study aimed to find a therapeutic drug that is more effective than regorafenib for CRC treatment. Here, we showed that SC-43 was more effective than regorafenib at inducing apoptosis in vitro and suppressing tumorigenesis in vivo. SC-43 significantly increased SHP-1 activity, downregulated p-STAT3(Tyr705) level, and induced apoptosis in CRC cells. An SHP-1 inhibitor or knockdown of SHP-1 by siRNA both significantly rescued the SC-43-induced apoptosis and decreased p-STAT3(Tyr705) level. Conversely, SHP-1 overexpression increased the effects of SC-43 on apoptosis and p-STAT3(Tyr705) level. These data suggest that SC-43-induced apoptosis mediated through the loss of p-STAT3(Tyr705) was dependent on SHP-1 function. Importantly, SC-43-enhanced SHP-1 activity was because of the docking potential of SC-43, which relieved the autoinhibited N-SH2 domain of SHP-1 and inhibited p-STAT3(Tyr705) signals. Importantly, we observed that a significant negative correlation existed between SHP-1 and p-STAT3(Tyr705)expression in CRC patients (P = .038). Patients with strong SHP-1 and weak p-STAT3(Tyr705) expression had significantly higher overall survival compared with patients with weak SHP-1 and strong p-STAT3(Tyr705) expression (P = .029). In conclusion, SHP-1 is suitable to be a useful prognostic marker and a pharmacological target for CRC treatment. Targeting SHP-1-STAT3 signaling by SC-43 may serve as a promising pharmacotherapy for CRC. PMID:26476076

  14. Pharmacological Targeting SHP-1-STAT3 Signaling Is a Promising Therapeutic Approach for the Treatment of Colorectal Cancer12

    PubMed Central

    Fan, Li-Ching; Teng, Hao-Wei; Shiau, Chung-Wai; Tai, Wei-Tien; Hung, Man-Hsin; Yang, Shung-Haur; Jiang, Jeng-Kai; Chen, Kuen-Feng

    2015-01-01

    STAT3 activation is associated with poor prognosis in human colorectal cancer (CRC). Our previous data demonstrated that regorafenib (Stivarga) is a pharmacological agonist of SH2 domain-containing phosphatase 1 (SHP-1) that enhances SHP-1 activity and induces apoptosis by targeting STAT3 signals in CRC. This study aimed to find a therapeutic drug that is more effective than regorafenib for CRC treatment. Here, we showed that SC-43 was more effective than regorafenib at inducing apoptosis in vitro and suppressing tumorigenesis in vivo. SC-43 significantly increased SHP-1 activity, downregulated p-STAT3Tyr705 level, and induced apoptosis in CRC cells. An SHP-1 inhibitor or knockdown of SHP-1 by siRNA both significantly rescued the SC-43–induced apoptosis and decreased p-STAT3Tyr705 level. Conversely, SHP-1 overexpression increased the effects of SC-43 on apoptosis and p-STAT3Tyr705 level. These data suggest that SC-43–induced apoptosis mediated through the loss of p-STAT3Tyr705 was dependent on SHP-1 function. Importantly, SC-43–enhanced SHP-1 activity was because of the docking potential of SC-43, which relieved the autoinhibited N-SH2 domain of SHP-1 and inhibited p-STAT3Tyr705 signals. Importantly, we observed that a significant negative correlation existed between SHP-1 and p-STAT3Tyr705expression in CRC patients (P = .038). Patients with strong SHP-1 and weak p-STAT3Tyr705 expression had significantly higher overall survival compared with patients with weak SHP-1 and strong p-STAT3Tyr705 expression (P = .029). In conclusion, SHP-1 is suitable to be a useful prognostic marker and a pharmacological target for CRC treatment. Targeting SHP-1-STAT3 signaling by SC-43 may serve as a promising pharmacotherapy for CRC. PMID:26476076

  15. Predictors of placebo response in pharmacological and dietary supplement treatment trials in pediatric autism spectrum disorder: a meta-analysis.

    PubMed

    Masi, A; Lampit, A; Glozier, N; Hickie, I B; Guastella, A J

    2015-01-01

    Large placebo responses in many clinical trials limit our capacity to identify effective therapeutics. Although it is often assumed that core behaviors in children with autism spectrum disorders (ASDs) rarely remit spontaneously, there has been limited investigation of the size of the placebo response in relevant clinical trials. These trials also rely on caregiver and clinical observer reports as outcome measures. The objectives of this meta-analysis are to identify the pooled placebo response and the predictors of placebo response in pharmacological and dietary supplement treatment trials for participants with a diagnosis of ASD. Randomized controlled trials (RCTs) in pediatric ASD, conducted between 1980 and August 2014, were identified through a search of Medline, EMBASE, Web of Science, Cochrane Database of Systematic Reviews and clinicaltrials.gov. RCTs of at least 14 days duration, comparing the treatment response for an oral active agent and placebo using at least one of the common outcome measures, were included. Analysis of 25 data sets (1315 participants) revealed a moderate effect size for overall placebo response (Hedges' g=0.45, 95% confidence interval (0.34-0.56), P<0.001). Five factors were associated with an increase in response to placebo, namely: an increased response to the active intervention; outcome ratings by clinicians (as compared with caregivers); trials of pharmacological and adjunctive interventions; and trials located in Iran. There is a clear need for the identification of objective measures of change in clinical trials for ASD, such as evaluation of biological activity or markers, and for consideration of how best to deal with placebo response effects in trial design and analyses. PMID:26393486

  16. Genetic and Pharmacological Intervention for Treatment/Prevention of Hearing Loss

    ERIC Educational Resources Information Center

    Cotanche, Douglas A.

    2008-01-01

    Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans. Recent experiments have…

  17. The Current State of Empirical Support for the Pharmacological Treatment of Selective Mutism

    ERIC Educational Resources Information Center

    Carlson, John S.; Mitchell, Angela D.; Segool, Natasha

    2008-01-01

    This article reviews the current state of evidence for the psychopharmacological treatment of children diagnosed with selective mutism within the context of its link to social anxiety disorder. An increased focus on potential medication treatment for this disorder has resulted from significant monetary and resource limitations in typical practice,…

  18. Pharmacologic Treatments for Pediatric Bipolar Disorder: A Review and Meta-Analysis

    ERIC Educational Resources Information Center

    Liu, Howard Y.; Potter, Mona P.; Woodworth, K. Yvonne; Yorks, Dayna M.; Petty, Carter R.; Wozniak, Janet R.; Faraone, Stephen V.; Biederman, Joseph

    2011-01-01

    Objective: A growing body of literature has documented pediatric bipolar disorder to be a severely impairing form of psychopathology. However, concerns remain as to the inadequacy of the extant literature on its pharmacotherapy. Furthermore, treatment studies have not been systematically reviewed for treatment effects on core and associated…

  19. Ocular pharmacology.

    PubMed

    Novack, Gary D; Robin, Alan L

    2016-05-01

    Ophthalmic diseases include both those analogous to systemic diseases (eg, inflammation, infection, neuronal degeneration) and not analogous (eg, cataract, myopia). Many anterior segment diseases are treated pharmacologically through eye drops, which have an implied therapeutic index of local therapy. Unlike oral dosage forms administered for systemic diseases, eyedrops require patients not only to adhere to treatment, but to be able to accurately perform-ie, instill drops correctly. Anatomical and physiological barriers make topical delivery to the anterior chamber challenging-in some cases more challenging than absorption through the skin, nasal passages, or gut. Treatment of the posterior segment (eg, vitreous, retina, choroid, and optic nerve) is more challenging due to additional barriers. Recently, intravitreal injections have become a standard of care with biologics for the treatment of macular degeneration and other diseases. Although the eye has esterases, hydroxylases, and transporters, it has relatively little CYP450 enzymes. Because it is challenging to obtain drug concentrations at the target site, ocular clinical pharmacokinetics, and thus pharmacokinetic-pharmacodynamic interactions, are rarely available. Ophthalmic pharmaceuticals require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Although applied locally, ocular medications may be absorbed systemically, which results in morbidity and mortality (eg, systemic hypotension, bronchospasm, and bradycardia). PMID:26360129

  20. The Efficacy of Pharmacological Treatment in Pediatric Nonalcoholic Fatty Liver Disease

    PubMed Central

    Cho, Taeshik; Paik, Seung Sam

    2012-01-01

    Purpose With growing number of obese children, the prevalence of nonalcoholic fatty liver disease (NAFLD) in pediatric population is increasing. Nonalcoholic steatohepatitis (NASH) is a severe form of NAFLD, and can cause morbid complications. It is important to identify patients in order to grade pathologic severities and treat those children who possibly have NASH. This study was performed to evaluate whether the pharmacological therapy is also effective as well as the body weight reduction in pediatric NAFLD. Methods Among the 52 children presenting with obesity and hepatopathy, NAFLD was diagnosed through liver biopsy in 29 children, who were 7 to 14 years of age, from January 2006 to December 2011. The patients were advised to reduce their body weight through diverse methods. Medication with Ursodeoxycholic acid (UDCA) and vitamin E was performed in children whose liver functions did not improve or their weight reductions were not successful. The therapeutic effects were monitored and assessed via the biochemical profiles and the physical measurements. Results The therapy of vitamin E and UDCA combined with body mass index (BMI) reduction showed significantly higher rate of improvement in clinical profiles, which could be seen in data of aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, alkaline phosphatase, total bilirubin and γ-glutamyl transpeptidase. Children whose BMI were successfully reduced showed favorable clinical improvements without any medication, but those without BMI reduction did not show any improvement despite medications. Conclusion This study showed that the first line of therapy should be the BMI reduction in NAFLD and drug therapy combined with BMI reduction could have additive therapeutic effect in children with NAFLD. PMID:24010096

  1. Treatment of radiculopathies: a study of efficacy and tollerability of paravertebral oxygen-ozone injections compared with pharmacological anti-inflammatory treatment.

    PubMed

    Melchionda, D; Milillo, P; Manente, G; Stoppino, L; Macarini, L

    2012-01-01

    The study was performed to evaluate the effectiveness of lumbar paravertebral injections of a gas mixture of Oxygen and Ozone in patients with lumbar radiculopathies caused by L4-L5 or L5-S1 disk herniations compared to a pharmacological therapy based on non-steroidal anti-inflammatory drugs. Lumbar radiculopathy caused by disc herniation is widely spread. Many therapeutic options are available before steering patients to the surgery. Low back pain and sciatica represent some of the most frequent causes of antinflammatory-analgesic drugs overuse. Recent findings have shown that medical Ozone can be used in the treatment of radicular syndrome caused by herniated intervertebral discs. Although widely spread, there are insufficient published data supporting the effectiveness of this approach in clinical practice. We studied 38 affected patients with acute L5 or S1 radicolopathy. The patients were randomly divided in two groups: A) 20 patients treated with lumbar paravertebral injections of Oxygen and Ozone; B) 18 patients treated pharmacologically with antinflammatory-analgesic drugs. All patients underwent a clinical and neurological examination at baseline (T1) and after 1 (T2), 2 (T3), 4 weeks (T4) and after 3 (T5) and 6 months (T6). An MRI and EMG examination were performed at baseline and after 6 months. The intensity of pain and the outcome of treatments were evaluated in all patients with the Visual Analogue Scale and with the Oswestry Disability Index. We found a reduction of pain and discomfort soon after one week with oxygen-ozone injections compared with pharmacological treatment, but this difference of response became statistically significant after two weeks (50 percent vs 16.6 percent) and is confirmed after 3 and 6 months, when 80 percent of patients treated with injections turned out pain free compared with half of the patients treated pharmacologically. No statistical difference were found in MRI and EMG examinations. No adverse effects were found in

  2. Cocaine Addiction Treatments to improve Control and reduce Harm (CATCH): New Pharmacological Treatment Options for Crack-Cocaine Dependence in the Netherlands

    PubMed Central

    2011-01-01

    Background Cocaine, particularly in its base form ('crack'), has become one of the drugs of most concern in the Netherlands, being associated with a wide range of medical, psychiatric and social problems for the individual, and with significant public order consequences for society. Available treatment options for cocaine dependent users are limited, and a substantial part of the cocaine dependent population is not reached by the addiction treatment system. Psychosocial interventions for cocaine dependence generally show modest results, and there are no registered pharmacological treatments to date, despite the wide range of medications tested for this type of dependence. The present study (Cocaine Addiction Treatments to improve Control and reduce Harm; CATCH) investigates the possibilities and problems associated with new pharmacological treatments for crack dependent patients. Methods/Design The CATCH-study consists of three separate randomised controlled, open-label, parallel-group feasibility trials, conducted at three separate addiction treatment institutes in the Netherlands. Patients are either new referrals or patients already in treatment. A total of 216 eligible outpatients are randomised using pre-randomisation double-consent design and receive either 12 weeks treatment with oral topiramate (n = 36; Brijder Addiction Treatment, The Hague), oral modafinil (n = 36; Arkin, Amsterdam), or oral dexamphetamine sustained-release (n = 36; Bouman GGZ, Rotterdam) as an add-on to cognitive behavioural therapy (CBT), or receive a 12-week CBT only (controls: n = 3 × 36). Primary outcome in these feasibility trials is retention in the underlying psychosocial treatment (CBT). Secondary outcomes are acceptance and compliance with the study medication, safety, changes in cocaine (and other drug) use, physical and mental health, social functioning, and patient satisfaction. Discussion To date, the CATCH-study is the first study in the Netherlands that explores new

  3. Pharmacological interventions for ADHD: how do adolescent and adult patient beliefs and attitudes impact treatment adherence?

    PubMed Central

    McCarthy, Suzanne

    2014-01-01

    Adherence to medication can be problematic for patients, especially so for patients with attention deficit hyperactivity disorder (ADHD). Effective medications are available for the treatment of ADHD; however, nonadherence rates for ADHD medication range from 13.2%–64%. The reasons for nonadherence can be complex. This review aims to look at how the beliefs and attitudes of adolescents and adults impact ADHD treatment adherence. PMID:25284990

  4. A Dose-Ranging Study of Behavioral and Pharmacological Treatment for Children with ADHD

    PubMed Central

    Pelham, William E.; Burrows-MacLean, Lisa; Gnagy, Elizabeth M.; Fabiano, Gregory A.; Coles, Erika K.; Wymbs, Brian T.; Chacko, Anil; Walker, Kathryn S.; Wymbs, Frances; Garefino, Allison; Hoffman, Martin T.; Waxmonsky, James G.; Waschbusch, Daniel A.

    2014-01-01

    Placebo and 3 doses of methylphenidate (MPH) were crossed with 3 levels of behavioral modification (no behavioral modification, NBM; low-intensity behavioral modification, LBM; and high-intensity behavior modification, HBM) in the context of a summer treatment program (STP). Participants were 48 children with ADHD, aged 5–12. Behavior was examined in a variety of social settings (sports activities, art class, lunch) that are typical of elementary school, neighborhood, and after-school settings. Children received each behavioral condition for 3 weeks, order counterbalanced across groups. Children concurrently received in random order placebo, .15 mg/kg/dose, .3 mg/kg/dose, or .6 mg/kg/dose MPH, 3 times daily with dose manipulated on a daily basis in random order for each child. Both behavioral and medication treatments produced highly significant and positive effects on children's behavior. The treatment modalities also interacted significantly. Whereas there was a linear dose-response curve for medication in NBM, the dose-response curves flattened considerably in LBM and HBM. Behavior modification produced effects as large as moderate doses, and on some measures, high doses of medication. These results replicate and extend to social-recreational settings previously reported results in a classroom setting from the same sample (Fabiano et al., 2007). Results illustrate the importance of taking dosage/intensity into account when evaluating combined treatments; there were no benefits of combined treatments when the dosage of either treatment was high but combination of the low-dose treatments produced substantial incremental improvement over unimodal treatment. PMID:24429997

  5. Safe pharmacologic treatment strategies for osteoarthritis pain in African Americans with hypertension, and renal and cardiac disease.

    PubMed Central

    Johnson, Jerry; Weinryb, Joan

    2006-01-01

    Arthritis is the leading cause of disability in the United States. Osteoarthritis, the most common form of arthritis, is a degenerative joint disease affecting both whites and African Americans similarly. African Americans have a high incidence rate of comorbidities, including hypertension, cardiovascular disease (CVD) risk factors and diabetes. Treatment of osteoarthritic pain in patients with comorbidities is often complicated by potential safety concerns. Traditional nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase 2 (COX-2) specific NSAIDs have been shown to increase blood pressure in hypertensive patients taking antihypertensive medications. Patients with CVD risk factors taking low-dose aspirin for secondary prevention may be at increased risk for gastrointestinal bleeding with NSAIDs. Diabetics face an increased risk of renal complications. Because NSAIDs are associated with adverse renal effects, they should be used cautiously in patients with advanced renal disease. Acetaminophen is the most appropriate initial analgesic for African Americans with chronic osteoarthritic pain and concurrent hypertension, CVD risk factors or diabetes, and is recommended by the American College of Rheumatology as first-line treatment. Many of the adverse effects commonly associated with NSAIDs are not associated with acetaminophen. Safety concerns surrounding pharmacologic treatment of osteoarthritis in African Americans are reviewed. PMID:16895283

  6. Curcumin-loaded lipid-core nanocapsules as a strategy to improve pharmacological efficacy of curcumin in glioma treatment.

    PubMed

    Zanotto-Filho, Alfeu; Coradini, Karine; Braganhol, Elizandra; Schröder, Rafael; de Oliveira, Cláudia Melo; Simões-Pires, André; Battastini, Ana Maria Oliveira; Pohlmann, Adriana Raffin; Guterres, Sílvia Stanisçuaski; Forcelini, Cassiano Mateus; Beck, Ruy Carlos Ruver; Moreira, José Cláudio Fonseca

    2013-02-01

    In this study, we developed curcumin-loaded lipid-core nanocapsules (C-LNCs) in an attempt to improve the antiglioma activity of this polyphenol. C-LNC showed nanotechnological properties such as nanometric mean size (196 nm), 100% encapsulation efficiency, polydispersity index below 0.1, and negative zeta potential. The in vitro release assays demonstrated a controlled release of curcumin from lipid-core nanocapsules. In C6 and U251MG gliomas, C-LNC promoted a biphasic delivery of curcumin: the first peak occurred early in the treatment (1-3h), whereas the onset of the second phase occurred after 48 h. In C6 cells, the cytotoxicity of C-LNC was comparable to non-encapsulated curcumin only after 96 h, whereas C-LNCs were more cytotoxic than non-encapsulated curcumin after 24h of incubation in U251MG. Induction of G2/M arrest and autophagy were observed in C-LNC as well as in free-curcumin treatments. In rats bearing C6 gliomas, C-LNC (1.5mg/kg/day, i.p.) decreased the tumor size and malignance and prolonged animal survival when compared to same dose of non-encapsulated drug. In addition, serum markers of tissue toxicity and histological parameters were not altered. Considered overall, the data suggest that the nanoencapsulation of curcumin in LNC is an important strategy to improve its pharmacological efficacy in the treatment of gliomas. PMID:23219677

  7. Novel pharmacologic approaches to the prevention and treatment of ulcerative colitis.

    PubMed

    Deng, Xiaoming; Szabo, Sandor; Khomenko, Tetyana; Tolstanova, Ganna; Paunovic, Brankica; French, Samuel W; Sandor, Zsuzsanna

    2013-01-01

    UC. The increased VP is initiated by early release of histamine and maintained/aggravated by VEGF, leading to perivascular edema, vascular stasis, hypoxia, inflammatory cell infiltration, and colonic erosions/ulcers. Inhibition of increased VP prevents or reduces development and progression of UC. In this review, we discuss novel pharmacologic approaches to prevent UC, differential actions of angiogenic growth factors in UC pathogenesis and blocking the early increase in VP in UC development, these new findings may provide new insights into the regulation of angiogenesis in UC and may lead to development of VP-related drugs to accelerate the healing of UC. PMID:22950505

  8. Placebo Improvement in Pharmacologic Treatment of Menopausal Hot Flashes: Time Course, Duration, and Predictors

    PubMed Central

    Freeman, Ellen W.; Ensrud, Kristine E.; Larson, Joseph C.; Guthrie, Katherine A.; Carpenter, Janet S.; Joffe, Hadine; Newton, Katherine M.; Sternfeld, Barbara; LaCroix, Andrea Z.

    2014-01-01

    Objectives This study characterized the time course, duration of improvement and clinical predictors of placebo response in treatment of menopausal hot flashes. Methods Data were pooled from two trials conducted in the MsFLASH network, providing a combined placebo group (N=247) and a combined active treatment group (N=297). Participants recorded hot flash frequency in diaries twice daily during treatment (week 0-8) and subsequent follow-up (week 9-11). The primary outcome variable was clinically significant improvement, defined as >=50% decrease in hot flash frequency from baseline and calculated for each week in the study. Subgroups were defined a priori using standard clinical definitions for significant improvement and partial improvement. Clinical and demographic characteristics of the participants were evaluated as predictors of improvement. Results Clinically significant improvement with placebo accrued each treatment week, with 33% significantly improved at week 8. Of placebo responders who were improved at both weeks 4 and 8, 77% remained clinically improved at week 11 after treatment ended. Independent predictors of significant placebo improvement in the final multivariable model were African American race (OR 5.61, 95% CI: 2.41-13.07, p<0.001); current smokers (OR 2.30, 95% CI: 1.05-5.06, p=0.038); and hot flash severity in screening (OR 1.45, 95% CI: 1.00-2.10, p=0.047). Conclusions Clinically significant improvement with placebo accrued throughout treatment with a time course similar to improvement with active drug. A meaningful number of participants in the placebo group sustained a clinically significant response after stopping placebo pills. The results suggest that non-specific effects are important components of treatment and warrant further studies to optimize their contributions in clinical care. PMID:25647753

  9. Preclinical Pharmacological Evaluation of Letrozole as a Novel Treatment for Gliomas

    PubMed Central

    Dave, Nimita; Chow, Lionel M.L.; Gudelsky, Gary A.; LaSance, Kathleen; Qi, Xiaoyang; Desai, Pankaj B.

    2015-01-01

    We present data that letrozole, an extensively used aromatase inhibitor in the treatment of estrogen receptor-positive breast tumors in postmenopausal women, may be potentially used in the treatment of glioblastomas. First, we measured the in vitro cytotoxicity of letrozole and aromatase (CYP19A1) expression and activity in human LN229, T98G, U373MG, U251MG, and U87MG, and rat C6 glioma cell lines. Estrogen receptor (ER)positive MCF-7 and ER-negative MDA-MB-231 cells served as controls. Cytotoxicity was determined employing the MTT assay, and aromatase activity using an immunoassay that measures the conversion of testosterone to estrogen. Second, in vivo activity of letrozole was assessed in Sprague-Dawley rats orthotopically implanted with C6 gliomas. The changes in tumor volume with letrozole treatment (4 mg/kg/day) were assessed employing μPET/CT imaging, employing [18F]-fluorodeoxyglucose (F18-FDG) as the radiotracer. Brain tissues were collected for histologic evaluations. All glioma cell lines included here expressed CYP19A1 and letrozole exerted considerable cytotoxicity and decrease in aromatase activity against these cells (IC50, 0.1–3.5 μmol/L). Imaging analysis employing F18-FDG μPET/CT demonstrated a marked reduction of active tumor volume (>75%) after 8 days of letrozole treatment. Immunohistochemical analysis revealed marked reduction in aromatase expression in tumoral regions of the brain after letrozole treatment. Thus, employing multifaceted tools, we demonstrate that aromatase may be a novel target for the treatment of gliomas and that letrozole, an FDA-approved drug with an outstanding record of safety may be repurposed for the treatment of such primary brain tumors, which currently have few therapeutic options. PMID:25695958

  10. Pharmacologic Treatment of Common Symptoms in Dialysis Patients: A Narrative Review.

    PubMed

    Moledina, Dennis G; Perry Wilson, Francis

    2015-01-01

    End-stage renal disease (ESRD) patients receiving hemodialysis experience a heavy burden of disease-related symptoms, which lead to reduced quality of life. This review focuses on aspects of ESRD-related pharmacokinetics and on efficacy of drugs for treatment of somatic symptoms. Fatigue, pruritus, insomnia, and cramps are the most common symptoms in ESRD, and studies suggest that they are often undertreated. However, few evidence-based guidelines exist to guide therapy in patients received dialysis. In the context of this review, we examine the role of l-Carnitine in the treatment of fatigue and cramps; human growth hormone analog Norditropin and anabolic steroid Nandrolone for the treatment of fatigue; Gabapentin and other agents for the management of pruritis; Vitamin and creatine supplementation in the management of dialysis-associated cramps, and somnambulates in the treatment of dialysis-related insomnia. Treatment decisions should be made in consultation with patients with a full accounting of the potential risks and benefits of these therapies. PMID:25913502

  11. Pharmacological Treatment with Annexin A1 Reduces Atherosclerotic Plaque Burden in LDLR-/- Mice on Western Type Diet

    PubMed Central

    Kusters, Dennis H. M.; Chatrou, Martijn L.; Willems, Brecht A. G.; De Saint-Hubert, Marijke; Bauwens, Matthias; van der Vorst, Emiel; Bena, Stefania; Biessen, Erik A. L.; Perretti, Mauro; Schurgers, Leon J.; Reutelingsperger, Chris P. M.

    2015-01-01

    Objective To investigate therapeutic effects of annexin A1 (anxA1) on atherogenesis in LDLR-/- mice. Methods Human recombinant annexin A1 (hr-anxA1) was produced by a prokaryotic expression system, purified and analysed on phosphatidylserine (PS) binding and formyl peptide receptor (FPR) activation. Biodistribution of 99mTechnetium-hr-anxA1 was determined in C57Bl/6J mice. 12 Weeks old LDLR-/- mice were fed a Western Type Diet (WTD) during 6 weeks (Group I) or 12 weeks (Group P). Mice received hr-anxA1 (1 mg/kg) or vehicle by intraperitoneal injection 3 times per week for a period of 6 weeks starting at start of WTD (Group I) or 6 weeks after start of WTD (Group P). Total aortic plaque burden and phenotype were analyzed using immunohistochemistry. Results Hr-anxA1 bound PS in Ca2+-dependent manner and activated FPR2/ALX. It inhibited rolling and adherence of neutrophils but not monocytes on activated endothelial cells. Half lives of circulating 99mTc-hr-anxA1 were <10 minutes and approximately 6 hours for intravenously (IV) and intraperitoneally (IP) administered hr-anxA1, respectively. Pharmacological treatment with hr-anxA1 had no significant effect on initiation of plaque formation (-33%; P = 0.21)(Group I) but significantly attenuated progression of existing plaques of aortic arch and subclavian artery (plaque size -50%, P = 0.005; necrotic core size -76% P = 0.015, hr-anxA1 vs vehicle) (Group P). Conclusion Hr-anxA1 may offer pharmacological means to treat chronic atherogenesis by reducing FPR-2 dependent neutrophil rolling and adhesion to activated endothelial cells and by reducing total plaque inflammation. PMID:26090792

  12. [Adult attention deficit/hyperactivity disorder, associated symptoms and comorbid psychiatric disorders: diagnosis and pharmacological treatment].

    PubMed

    Paslakis, G; Schredl, M; Alm, B; Sobanski, E

    2013-08-01

    Adult attention deficit/hyperactivity disorder (ADHD) is characterised by inattention and/or hyperactivity and impulsivity and is a frequent psychiatric disorder with childhood onset. In addition to core symptoms, patients often experience associated symptoms like emotional dysregulation or low self-esteem and suffer from comorbid disorders, particularly depressive episodes, substance abuse, anxiety or sleep disorders. It is recommended to include associated symptoms and comorbid psychiatric disorders in the diagnostic set-up and in the treatment plan. Comorbid psychiatric disorders should be addressed with disorder-specific therapies while associated symptoms also often improve with treatment of the ADHD core symptoms. The most impairing psychiatric disorder should be treated first. This review presents recommendations for differential diagnosis and treatment of adult ADHD with associated symptoms and comorbid psychiatric disorders with respect to internationally published guidelines, clinical trials and expert opinions. PMID:23864520

  13. [Pharmacological treatment of delirium in palliative care patients. A systematic literature review].

    PubMed

    Perrar, K M; Golla, H; Voltz, R

    2013-04-01

    This systematic literature review aims to collect and analyse relevant clinical trials for the drug treatment of delirium in palliative care. The search was conducted including July 2012 in Medline (from 1966) and Embase (from 1974). The search retrieved 448 studies, of which 3 studies could be included in the analysis. Treatment with the antipsychotic drug haloperidol can be recommended, which is also true to a somewhat lower extent for the antipsychotics olanzapine and aripiprazole. Treatment with lorazepam only should be avoided. This literature analysis reflects the positive clinical experience, especially when using haloperidol. To confirm these recommendations, further substantial clinical studies are needed.The English full-text version of this article can be found at SpringerLink (under "Supplemental"). PMID:23503785

  14. Oral pharmacological treatments for parasitic diseases of rainbow trout Oncorhynchus mykiss. I: Hexamita salmonis.

    PubMed

    Tojo, J L; Santamarina, M T

    1998-05-14

    Various drugs were evaluated as regards efficacy for the treatment of Hexamita salmonis infection in rainbow trout. The results confirm the efficacy of nitroimidazoles: infection was completely eradicated not only by metronidazole (which has been recommended previously for the treatment of hexamitosis), but also by benznidazole, ronidazole and secnidazole, which have not been assayed previously. The non-nitroimidazoles albendazole, aminosidine, diethylcarbamazine and nitroscanate also completely eliminated infection. The remaining non-nitroimidazoles tested (amprolium, bithionol, febantel, flubendazole, levamisole, netobimin, niclosamide, nitroxynil, oxibendazole, parbendazole, piperazine, praziquentel, tetramisole, thiophanate, toltrazuril, trichlorfon and triclabendazole) were not effective. PMID:9653458

  15. [Pharmacological treatment of dementia: when, how and for how long. Recommendations of the Working Group on Dementia of the Catalan Society of Geriatrics and Gerontology].

    PubMed

    Rodríguez, Daniel; Formiga, Francesc; Fort, Isabel; Robles, María José; Barranco, Elena; Cubí, Dolors

    2012-01-01

    Dementia in general--and Alzheimer's disease (AD) in particular--are bound to loom large among the most acute healthcare, social, and public health problems of the 21st century. AD shows a degenerative progression that can be slowed down--yet not halted--by today's most widely accepted specific treatments (those based on cholinesterase inhibitors as well as those using memantine). There is enough evidence to consider these treatments advisable for the mild, moderate and severe phases of the illness. However, in the final stage of the disease, a decision has to be made on whether to withdraw such treatment or not. In this paper, the Working Group on Dementia for the Catalan Society of Geriatrics and Gerontology reviews the use of these specific pharmacological treatments for AD, and, drawing on the scientific evidence thus gathered, makes a series of recommendations on when, how, and for how long, the currently existing specific pharmacological treatments should be used. PMID:22633250

  16. Social phobia: diagnosis and epidemiology, neurobiology and pharmacology, comorbidity and treatment.

    PubMed

    Brunello, N; den Boer, J A; Judd, L L; Kasper, S; Kelsey, J E; Lader, M; Lecrubier, Y; Lepine, J P; Lydiard, R B; Mendlewicz, J; Montgomery, S A; Racagni, G; Stein, M B; Wittchen, H U

    2000-10-01

    Social phobia is a common disorder associated with significant psychosocial impairment, representing a substantial public health problem largely determined by the high prevalence, and the lifelong chronicity. Social phobia starts in early childhood or adolescence and is often comorbid with depression, other anxiety disorders, alcohol and substance abuse or eating disorders. This cascade of comorbidity, usually secondary to social phobia, increases the disability associated with the condition. The possibility that social phobia may be a trigger for later developing comorbid disorders directs attention to the need for early effective treatment as a preventive measure. The most recent drug class to be investigated for the psychopharmacological treatment of social phobia is the SSRI group for which there is growing support. The other drug classes that have been evaluated are monoamine oxidase inhibitors (MAOIs), benzodiazepines, and beta-blockers. The SSRIs represent a new and attractive therapeutic choice for patients with generalized social phobia. Recently the first, large scale, placebo-controlled study to assess the efficacy of drug treatment in generalized social phobia has been completed with paroxetine. Paroxetine was more effective in reducing the symptoms than placebo and was well tolerated. Many now regard SSRIs as the drugs of choice in social phobia because of their effectiveness and because they avoid the problems of treatment with benzodiazepines or classical MAOIs. PMID:10940449

  17. Do Pharmacological and Behavioral Interventions Differentially Affect Treatment Outcome for Children with Social Phobia?

    ERIC Educational Resources Information Center

    Scharfstein, Lindsay A.; Beidel, Deborah C.; Rendon Finnell, Laura; Distler, Aaron; Carter, Nathan T.

    2011-01-01

    In a randomized trial for children with social phobia (SP), Social Effectiveness Therapy for Children (SET-C; a treatment consisting of exposure and social skills training) and fluoxetine were more effective than pill placebo in reducing social distress and behavioral avoidance, but only SET-C demonstrated significantly improved overall social…

  18. Effects of FDA Advisories on the Pharmacologic Treatment of ADHD, 2004–2008

    PubMed Central

    Kornfield, Rachel; Watson, Sydeaka; Higashi, Ashley S.; Conti, Rena M.; Dusetzina, Stacie B.; Garfield, Craig F.; Dorsey, E. Ray; Huskamp, Haiden A.; Alexander, G. Caleb

    2014-01-01

    Objective This study assessed the effect of public health advisories issued between 2005 and 2007 by the U.S. Food and Drug Administration (FDA) on treatments of attention-deficit hyperactivity disorder (ADHD) and physician prescribing practices. Methods Data obtained from the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physicians, were used to examine trends in office visits by children and adolescents (under age 18) during which ADHD was treated with Adderall, other psychostimulants, or atomoxetine. Segmented time series regressions were conducted to determine changes in use associated with three advisories issued between 2005 and 2007. Results In 2004, before the first FDA advisory, Adderall accounted for 36% of ADHD pharmacotherapy treatment visits. Other stimulants accounted for 46%, and atomoxetine accounted for 19%. Overall pharmacotherapy treatment rates were stable over the study period, but by 2008 the treatment visits accounted for by Adderall (that is, market share) declined to 24%, and the market share for atomoxetine declined to 8%. The market share for substitute therapies—clonidine, guanfacine, and bupropion—was stable over this period, ranging from 5% to 7%. Despite the declines in the use of Adderall and atomoxetine over the study period, results from the regression models suggest that the advisories did not have a statistically significant effect on ADHD medication prescribing. Conclusions FDA advisories regarding potential cardiovascular and other risks of ADHD medications had little discernible incremental effect on the use of these medicines in this nationally representative ambulatory audit. PMID:23318985

  19. Pharmacological treatment with L-DOPA may reduce striatal dopamine transporter binding in in vivo imaging studies.

    PubMed

    Nikolaus, S; Antke, C; Hautzel, H; Mueller, H-W

    2016-01-01

    Numerous neurologic and psychiatric conditions are treated with pharmacological compounds, which lead to an increase of synaptic dopamine (DA) levels. One example is the DA precursor L-3,4-dihydroxyphenylalanine (L-DOPA), which is converted to DA in the presynaptic terminal. If the increase of DA concentrations in the synaptic cleft leads to competition with exogenous radioligands for presynaptic binding sites, this may have implications for DA transporter (DAT) imaging studies in patients under DAergic medication. This paper gives an overview on those findings, which, so far, have been obtained on DAT binding in human Parkinson's disease after treatment with L-DOPA. Findings, moreover, are related to results obtained on rats, mice or non-human primates. Results indicate that DAT imaging may be reduced in the striata of healthy animals, in the unlesioned striata of animal models of unilateral Parkinson's disease and in less severly impaired striata of Parkinsonian patients, if animal or human subjects are under acute or subchronic treatment with L-DOPA. If also striatal DAT binding is susceptible to alterations of synaptic DA levels, this may allow to quantify DA reuptake in analogy to DA release by assessing the competition between endogenous DA and the administered exogenous DAT radioligand. PMID:26642370

  20. Pharmacology and clinical efficacy of dimethyl fumarate (BG-12) for treatment of relapsing–remitting multiple sclerosis

    PubMed Central

    Ruggieri, Serena; Tortorella, Carla; Gasperini, Claudio

    2014-01-01

    The last two decades have seen the introduction of several therapies for multiple sclerosis (MS). These therapies are intended to work at different levels of the disease, typically targeting direct symptom management, brief corticosteroid administration for acute exacerbations, and the regular use of disease-modifying drugs. Nevertheless, in clinical practice, disease-modifying drugs or immunosuppressive treatments are frequently associated with suboptimal response in terms of efficacy and several side effects leading to poor patient adherence, so the proportion of relapsing–remitting MS patients not adequately responding to disease-modifying therapy have been reported to range from 7% to 49%. Natalizumab and fingolimod are the newest US Food and Drug Administration-approved agents that have been added to the MS treatment armamentarium, but their use is limited by a less known safety profile and recognized specific risk. Thus, there is an important need for new therapeutic strategies, especially those that may offer greater patient satisfaction and safer risk profile in order to optimize therapeutic outcomes. A number of potential therapies for MS are now in late-stage development. Effective, safe, and well-tolerated therapies may improve compliance and empower patients with a level of independence not presently possible. To meet these characteristics, most of these therapies are oral compounds. Herein, we review the pharmacology and efficacy of dimethyl fumarate (BG-12) to date and its role in the evolving marketplace. PMID:24707183

  1. Pharmacological treatment with mirtazapine rescues cortical atrophy and respiratory deficits in MeCP2 null mice

    PubMed Central

    Bittolo, Tamara; Raminelli, Carlo Antonio; Deiana, Chiara; Baj, Gabriele; Vaghi, Valentina; Ferrazzo, Sara; Bernareggi, Annalisa; Tongiorgi, Enrico

    2016-01-01

    Loss of MeCP2 (Methyl CpG binding protein 2) in Rett syndrome (RTT) causes brain weight decrease, shrinkage of the cortex with reduced dendritic arborization, behavioral abnormalities, seizures and cardio-respiratory complications. The observed monoamine neurotransmitters reduction in RTT suggested antidepressants as a possible therapy. We treated MeCP2-null mice from postnatal-day 28 for two weeks with desipramine, already tested in RTT, or mirtazapine, an antidepressant with limited side-effects, known to promote GABA release. Mirtazapine was more effective than desipramine in restoring somatosensory cortex thickness by fully rescuing pyramidal neurons dendritic arborization and spine density. Functionally, mirtazapine treatment normalized heart rate, breath rate, anxiety levels, and eliminated the hopping behavior observed in MeCP2-null mice, leading to improved phenotypic score. These morphological and functional effects of mirtazapine were accompanied by reestablishment of the GABAergic and glutamatergic receptor activity recorded in cortex and brainstem tissues. Thus, mirtazapine can represent a new potential pharmacological treatment for the Rett syndrome. PMID:26806603

  2. Pharmacological treatment with mirtazapine rescues cortical atrophy and respiratory deficits in MeCP2 null mice.

    PubMed

    Bittolo, Tamara; Raminelli, Carlo Antonio; Deiana, Chiara; Baj, Gabriele; Vaghi, Valentina; Ferrazzo, Sara; Bernareggi, Annalisa; Tongiorgi, Enrico

    2016-01-01

    Loss of MeCP2 (Methyl CpG binding protein 2) in Rett syndrome (RTT) causes brain weight decrease, shrinkage of the cortex with reduced dendritic arborization, behavioral abnormalities, seizures and cardio-respiratory complications. The observed monoamine neurotransmitters reduction in RTT suggested antidepressants as a possible therapy. We treated MeCP2-null mice from postnatal-day 28 for two weeks with desipramine, already tested in RTT, or mirtazapine, an antidepressant with limited side-effects, known to promote GABA release. Mirtazapine was more effective than desipramine in restoring somatosensory cortex thickness by fully rescuing pyramidal neurons dendritic arborization and spine density. Functionally, mirtazapine treatment normalized heart rate, breath rate, anxiety levels, and eliminated the hopping behavior observed in MeCP2-null mice, leading to improved phenotypic score. These morphological and functional effects of mirtazapine were accompanied by reestablishment of the GABAergic and glutamatergic receptor activity recorded in cortex and brainstem tissues. Thus, mirtazapine can represent a new potential pharmacological treatment for the Rett syndrome. PMID:26806603

  3. Nasal congestion in infants and children: a literature review on efficacy and safety of non-pharmacological treatments.

    PubMed

    Chirico, G; Quartarone, G; Mallefet, P

    2014-12-01

    The most common causes of nasal obstruction and runny nose in infants and children are infections, mainly of viral origin, or allergies. In neonates and infants viral upper respiratory tract infections (URTI) are frequently observed during episodes of nasal obstruction. Saline irrigation of the nose is believed to alleviate URTI symptoms by helping to eliminate excess mucus, to reduce congestion and by contributing to improve breathing. Objective of the study was to review the efficacy and safety of non-pharmacological options for the treatment of nasal congestion and its sequelae, in infants and children, with a special focus on hypertonic and isotonic solutions and other medical devices, including nasal aspirators. Available data indicate that nasal symptoms in children with allergic rhinitis or acute sinusitis significantly improved following nasal saline irrigation. The use of medical devices is less documented. Nasal aspiration with a medical device, associated with an isotonic saline solution, during viral rhinitis, has been shown to lower the risk of developing acute otitis media and rhinosinusitis, in comparison with a group treated with physiological saline solution alone. Safety and tolerability have been evaluated and no serious adverse events have been reported. Literature data highlighted the good tolerability. The use of isotonic and hypertonic saline solutions to relief nasal congestion in infants and children is widespread; it is a safe and valuable therapeutic support, and can reduce the use of medications (antihistamines, decongestant, antibiotics, corticosteroids) during the treatment of URTIs. PMID:25336097

  4. Using neuroimaging to evaluate and guide pharmacological and psychotherapeutic treatments for mood disorders in children.

    PubMed

    Singh, Manpreet K; Garrett, Amy S; Chang, Kiki D

    2015-08-01

    Mood disorders are increasing in childhood, and often require multimodal and comprehensive treatment plans to address a complex array of symptoms and associated morbidities. Pharmacotherapy, in combination with psychotherapeutic interventions, is essential for treatment and stabilization. Current evidence supports the use of a number of interventions in children and adolescents diagnosed with DSM-5 mood spectrum disorders, which are associated with impairments in prefrontal-striatal-limbic networks, which are key for emotional functioning and regulation. Yet, little is known about the neurobiological effects of interventions on the developing brain. This chapter provides a synopsis of the literature demonstrating the neural effects of psychotropic medications and psychotherapy in youth with depressive or bipolar spectrum disorders. Additional longitudinal and biological studies are warranted to characterize the effects of these interventions on all phases and stages of mood illness development in children and adolescents. PMID:25659836

  5. Pharmacological treatment of severely depressed patients: a meta-analysis comparing efficacy of mirtazapine and amitriptyline.

    PubMed

    Kasper, S; Zivkov, M; Roes, K C; Pols, A G

    1997-05-01

    Efficacy data were available from 405 severely depressed patients (baseline 17-item Hamilton Rating Scale for Depression-HAMD scores > or = 25) participating in randomized, double-blind, amitriptyline-controlled studies of mirtazapine. Main efficacy variable were changes from baseline in the group mean 17-item HAMD scores and responder rates. Secondary efficacy variables were changes in depressed mood item on the HAMD and in factors derived from the 17-item HAMD scale. Treatment with either mirtazapine or amitriptyline resulted in robust reductions of baseline HAMD scores and in similar and high percentages of responders. Both drugs produced favourable effects on depressed mood and on symptoms commonly associated with depression, such as anxiety, sleep and vegetative disturbances. There were neither statistically significant nor clinically relevant differences between mirtazapine and amitriptyline at any assessment point nor at endpoint. The results demonstrate that the new antidepressant mirtazapine and the tricyclic antidepressant amitriptyline are equally effective in the treatment of severely depressed patients. PMID:9169299

  6. Magnetoencephalographic Correlates of Emotional Processing in Major Depression Before and After Pharmacological Treatment

    PubMed Central

    Domschke, Katharina; Zwanzger, Peter; Rehbein, Maimu A; Steinberg, Christian; Knoke, Kathrin; Dobel, Christian; Klinkenberg, Isabelle; Kugel, Harald; Kersting, Anette; Arolt, Volker; Pantev, Christo

    2016-01-01

    Background: In major depressive disorder (MDD), electrophysiological and imaging studies suggest reduced neural activity in the parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were analyzed for the first time in a pre-/post-treatment design by means of magnetoencephalography (MEG), allowing for detecting temporal dynamics of brain activation. Methods: Twenty-five medication-free Caucasian in-patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant, unpleasant, and neutral pictures. Fifteen patients were followed-up with a second MEG session after 4 weeks of antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. The clinical course of depression was assessed using the Hamilton Depression scale. Results: Prior to treatment, an overall neocortical hypoactivation during emotional processing, particularly at the parietal regions and areas at the right temporoparietal junction, as well as abnormal valence-specific reactions at the right parietal and bilateral dorsolateral prefrontal cortex (dlPFC) regions were observed in patients compared to controls. These effects occurred <150ms, suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at the right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy. Conclusions: The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto-parieto-temporal network, possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success. PMID:26259960

  7. A Review of New Pharmacologic Treatments for Patients With Chronic Heart Failure With Reduced Ejection Fraction.

    PubMed

    Nguyen, Elaine; Weeda, Erin R; White, C Michael

    2016-08-01

    Heart failure (HF) impacts an estimated 5.7 million Americans, and its prevalence is projected to increase to more than 8 million Americans in the next 15 years. Key clinical trials have established an evidence-based foundation for treatment of heart failure with reduced ejection fraction (HFrEF). Ivabradine and sacubitril/valsartan, which inhibit the f-channel and the angiotensin receptor and neprilysin, respectively, were recently approved by the Food and Drug Administration for HFrEF. In systolic heart failure, treatment with the If inhibitor ivabradine significantly reduced the combined endpoint of cardiovascular mortality or heart failure hospital admission vs placebo (P < .05). In the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with angiotensin-converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure trial, sacubitril/valsartan significantly reduced the combined endpoint of cardiovascular death or heart failure hospitalization vs enalapril (P < .001). The place of therapy with ivabradine and sacubitril/valsartan is defined by these trials and their interplay with guideline-directed medical therapy. Ivabradine and sacubitril/valsartan increase pharmacotherapy options for the treatment of HFrEF but are not yet first-line agents. Clinical application will be better defined in the coming years as practitioners increase their familiarity with ivabradine and sacubitril/valsartan. PMID:26626162

  8. Overview of Pharmacological Treatment Options for Pediatric Patients with Refractory Kawasaki Disease

    PubMed Central

    Saneeymehri, Seyyedeh; Baker, Katherine

    2015-01-01

    Kawasaki disease is an autoimmune disease found predominantly in children under the age of 5 years. Its incidence is higher in those who live in Asian countries or are of Asian descent. Kawasaki disease is characterized as an acute inflammation of the vasculature bed affecting mainly the skin, eyes, lymph nodes, and mucosal layers. Although the disease is usually self-limiting, patients may develop cardiac abnormalities that can lead to death. The exact cause of the disease is unknown; however, researchers hypothesize that an infectious agent is responsible for causing Kawasaki disease. Initial treatment options with intravenous immune globulin and aspirin are sufficient to cure most patients who acquire this disease. Unfortunately, in up to one-quarter of patients, the disease will be refractory to initial therapy and will require further management with corticosteroid, immunomodulatory, or cytotoxic agents. The lack of randomized, controlled trials makes treatment of refractory disease difficult to manage. Until larger randomized, controlled trials are published to give more guidance on therapy for this stage of disease, clinicians should use the data available from observational studies and case reports in conjunction with their clinical expertise to make treatment decisions. PMID:26170768

  9. Efficacy of Raynaud's phenomenon and digital ulcer pharmacological treatment in systemic sclerosis patients: a systematic literature review.

    PubMed

    García de la Peña Lefebvre, Paloma; Nishishinya, María Betina; Pereda, Claudia Alejandra; Loza, Estíbaliz; Sifuentes Giraldo, Walter Alberto; Román Ivorra, José Andrés; Carreira, Patricia; Rúa-Figueroa, Iñigo; Pego-Reigosa, Jose María; Muñoz-Fernández, Santiago

    2015-09-01

    To evaluate the efficacy of current treatments for the Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc), a systematic literature search was performed using Medline, EMBASE, and Cochrane Central Register of Controlled Trials (from 1961 to October 2011). We included meta-analyses, systematic reviews, clinical trials, and high-quality cohort studies published in English or Spanish. Patient populations had to include adults diagnosed with limited cutaneous or diffuse SSc who had associated RP and/or digital ulcers under pharmacological treatment. Efficacy of treatments was evaluated based on: number of RP episodes, RP severity, episode-free time, ulcer improvement/healing, and appearance of new ulcers. We used the Jadad scale of methodological quality to evaluate the quality of randomized clinical trials, and the 2009 Oxford Centre for Evidence-Based Medicine classification for other studies. Of a total of 1617 studies identified, only 27 fulfilled inclusion criteria. Drugs received the following grade recommendations: Grade A for nifedipine, nicardipine, quinapril, IV iloprost, bosentan, tadalafil, and MQx-503; Grade B for beraprost, cicaprost, DMSO, cyclofenil, and atorvastatin; and Grade C for misoprostol, prazosin, OPC-2826, enalapril, sildenafil, antioxidant, and stanazolol. Calcium channel blockers, prostanoids, tadalafil, and bosentan received the highest recommendation level for their effectiveness. However, most systematic reviews reviewed just a handful of studies with small sample sizes and short follow-ups. Our review shows that the existing evidence on the efficacy of RP treatment in SSc patients is inconclusive which calls for further research, especially in the form of prospective studies of high quality with long-term follow-ups. PMID:25824427

  10. Aminochrome as New Preclinical Model to Find New Pharmacological Treatment that Stop the Development of Parkinson's Disease.

    PubMed

    Segura-Aguilar, Juan; Muñoz, Patricia; Paris, Irmgard

    2016-01-01

    The pharmacological treatment of Parkinson's disease (PD) is limited to dopamine agonists and anti-cholinergic drugs that do not stop the progress of disease. LDopa was introduced to the treatment in 1967; this drug is still the best and most commonly used drug since it generates a real improvement in patient quality of life, but the disadvantage of L-dopa is that this positive effect is followed by severe side effects such as dyskinesia. The search for a new drug in the treatment of PD is limited to compounds which decrease the side effects of the drugs used in the treatment of the disease, such as L-dopa-induced dyskinesia. One possible explanation for pharmaceutical companies not developing new drugs to stop disease development is because the mechanism which induces the loss of dopaminergic neurons containing neuromelanin of the nigrostriatal system is still unknown. The discovery of genes (alpha-synuclein, parkin, pink-1, DJ- 1, LRRK2, GBA1, etc.) associated with familial forms of PD resulted in an enormous input into basic research in order to understand the role of these proteins in the disease. It is generally accepted that the loss of dopaminergic neurons containing neuromelanin involves mitochondrial dysfunction, protein degradation dysfunction, the aggregation of alpha-synuclein to neurotoxic oligomers, oxidative neuroinflammation and endoplasmic reticulum stress, but the question of what induces these mechanisms remains unanswered. Aminochrome, the product of dopamine oxidation and the precursor of neuromelanin, is directly involved in five of the six mechanisms and may be a better PD preclinical model. PMID:26695514

  11. Pharmacologic Plus Optical Penalization Treatment for Amblyopia: Results of a Randomized Trial

    PubMed Central

    2008-01-01

    Objective To compare weekend atropine augmented by a plano lens for the sound eye with weekend atropine alone for moderate amblyopia in children 3 to <7 years old. Methods In a multi-center clinical trial, 180 children with moderate amblyopia (20/40 to 20/100) were randomized to weekend atropine augmented by a plano lens or weekend atropine alone. Main Outcome Measure Masked assessment of amblyopic eye visual acuity using the Amblyopia Treatment Study HOTV testing protocol at 18 weeks. Results At 18 weeks, amblyopic eye improvement averaged 2.8 lines in the atropine plus plano lens group and 2.4 lines in the atropine alone group (mean difference between groups adjusted for baseline acuity 0.3 lines; 95% confidence interval, −0.2 to 0.8). Amblyopic eye acuity was 20/25 or better in 24 (29%) patients in the atropine-only group and 35 (40%) patients in the atropine plus plano lens group (P=0.03). More patients in the atropine plus plano lens group had reduced sound eye acuity at 18 weeks; however, there were no cases of persistent reverse amblyopia. Conclusions As an initial treatment for moderate amblyopia, the augmentation of weekend atropine with a plano lens does not substantially improve amblyopic eye acuity when compared with atropine alone. Application to Clinical Practice Treatment of children with unilateral amblyopia Trial Registry Name Trial Comparing Atropine to Atropine Plus a Plano Lens for the Sound Eye for Amblyopia in Children 3 to <7 Years Old PMID:19139333

  12. Pharmacological management of binge eating disorder: current and emerging treatment options

    PubMed Central

    McElroy, Susan L; Guerdjikova, Anna I; Mori, Nicole; O’Melia, Anne M

    2012-01-01

    Growing evidence suggests that pharmacotherapy may be beneficial for some patients with binge eating disorder (BED), an eating disorder characterized by repetitive episodes of uncontrollable consumption of abnormally large amounts of food without inappropriate weight loss behaviors. In this paper, we provide a brief overview of BED and review the rationales and data supporting the effectiveness of specific medications or medication classes in treating patients with BED. We conclude by summarizing these data, discussing the role of pharmacotherapy in the BED treatment armamentarium, and suggesting future areas for research. PMID:22654518

  13. Symptomatic and nonamyloid/tau based pharmacologic treatment for Alzheimer disease.

    PubMed

    Aisen, Paul S; Cummings, Jeffrey; Schneider, Lon S

    2012-03-01

    In this work we consider marketed drugs for Alzheimer disease (AD) including acetylcholinesterase inhibitors (AChE-Is) and antiglutamatergic treatment involving the N-methyl-d-aspartate (NMDA) receptor. We discuss medications and substances available for use as cognitive enhancers that are not approved for AD or cognitive impairment, and other neurotransmitter-related therapies in development or currently being researched. We also review putative therapies that aim to slow disease progression by mechanisms not directly related to amyloid or tau. PMID:22393531

  14. Oral pharmacological treatments for parasitic diseases of rainbow trout oncorhynchus mykiss. III. Ichthyobodo necator.

    PubMed

    Tojo, J L; Santamarina, M T

    1998-07-30

    A total of 32 drugs were evaluated as regards their efficacy for oral treatment of Ichthyobodo necator infestation of rainbow trout. In preliminary trials, all drugs were supplied to infected fish at 40 g per kg of feed for 10 d. The majority of the drugs tested (1,3-di-6-quinolylurea, aminosidine, amprolium, benznidazole, bithionol, chloroquine, diethylcarbamazine, dimetridazole, diminazene aceturate, febantel, flubendazole, ketoconazole, levamisole, mebendazole, netobimin, niclosamide, niridazole, nitroscanate, nitroxynil, oxibendazole, parbendazole, piperazine, praziquantel, ronidazole, sulphaquinoxaline, tetramisole, thiophanate, toltrazuril and trichlorfon) were ineffectdive. Metronidazole and secnidazole were 100% effective (unlike the other nitroimidazoles tested, namely dimetridazole, benznidazole and ronidazole). The non-carbamate benzimidazole triclabendazole was likewise 100% effective. PMID:9745716

  15. Evaluation of the endometriosis treatment success rate by the laparoscopic-pharmacological method

    NASA Astrophysics Data System (ADS)

    Mutrynowski, Andrzej; Zabielska, Renata; Smolarczyk, Roman

    1996-03-01

    The study aimed at evaluating the success rate of the operative laparoscopy assisted by electrocoagulation and laser as well as danazol and lynestrenol in the endometriosis treatment. One-hundred-ninety women with the recognized endometriosis were included into the study. In the I degree(s) endometriosis the operative or hormonal therapy was applied, in the II-IV degree(s) the combined therapy was used. The complete cure was achieved in 159 of the patients (84%): 28 women conceived, in 131 of the cases remission was recognized during the second laparoscopy. Eighteen women found improvement (9%) while 13 women (7%) reported the lack of improvement.

  16. Symptomatic and Nonamyloid/Tau Based Pharmacologic Treatment for Alzheimer Disease

    PubMed Central

    Aisen, Paul S.; Cummings, Jeffrey; Schneider, Lon S.

    2012-01-01

    In this work we consider marketed drugs for Alzheimer disease (AD) including acetylcholinesterase inhibitors (AChE-Is) and antiglutamatergic treatment involving the N-methyl-d-aspartate (NMDA) receptor. We discuss medications and substances available for use as cognitive enhancers that are not approved for AD or cognitive impairment, and other neurotransmitter-related therapies in development or currently being researched. We also review putative therapies that aim to slow disease progression by mechanisms not directly related to amyloid or tau. PMID:22393531

  17. Pharmacologic studies in Bartter's syndrome: opposite effects of treatment with antikaliuretic and antiprostaglandin drugs. Part I.

    PubMed

    Simatupang, T A; Radó, J P; Boer, P; Geyskes, G G; Vos, J; Dorhout Mees, E J

    1978-01-01

    The effect of antikaliuretic agents (spironolactone, amiloride) and antiprostaglandin agents (indomethacin, ibuprofen) on plasma renin activity and potassium metabolism was studied in a patient with familial Bartter's syndrome. The decrease in renal potassium clearance in response to antikaliuretic treatment was only of a temporary nature, in contrast to the marked potassium retention seen after indomethacin therapy. Plasma renin activity showed a consistent increase after kaliuretics and a marked decrease in response to antiprostaglandin agents. The opposite effect of the drugs on plasma renin activity, due to their different sites of action on the pathophysiologic chain of events in Bartter's syndrome, given an explanation for the contrasting therapeutic results. PMID:631965

  18. Aggressive experience affects the sensitivity of neurons towards pharmacological treatment in the hypothalamic attack area.

    PubMed

    Haller, J; Abrahám, I; Zelena, D; Juhász, G; Makara, G B; Kruk, M R

    1998-09-01

    Early investigators of brain stimulation-evoked complex behaviours (attack, escape, feeding, self-grooming, sexual behaviour) reported that experience may affect the behavioural outcome of brain stimulation. This intriguing example of functional neuronal plasticity was later totally neglected. The present experiment investigated the behavioural outcome of in vivo microdialysis perfusion of the glutamate agonist kainate and/or the GABAA antagonist bicuculline into the hypothalamic attack area (HAA) of (1) animals naive to dyadic encounters; (2) animals with a recent aggressive experience (the probe being implanted 6-24 h after the last of a series of dyadic encounters); and (3) animals with an earlier aggressive experience (probe being implanted 2 weeks after the last aggressive experience). On the experimental day, rats received two 5-min infusions during a dyadic encounter lasting 35 min with an unknown opponent. Flow rate was 1.5-2 microliters/min, drug concentrations were 1.8 x 10(-5) and 1.5 x 10(-5) M for kainate and bicuculline, respectively. Behaviour was analysed before, during and after perfusions. Only the combined kainate + bicuculline treatment had significant effects on behaviour at the doses studied. A significant increase in aggressive behaviour was elicited only in animals with a recent aggressive experience, while naive animals and with an earlier experience responded to the treatments by grooming. These results appear to support early observations indicating that one important aspect of brain stimulation effects is previous experience. PMID:9832932

  19. Pharmacological interventions for binge eating: lessons from animal models, current treatments, and future directions.

    PubMed

    Berner, Laura A; Bocarsly, Miriam E; Hoebel, Bartley G; Avena, Nicole M

    2011-01-01

    Binge eating behavior has been noted in some eating disorders as well as in obesity. The goal of this paper is to review current, non-serotonergic pharmaceutical approaches to treat binge eating. Further, using information derived from preclinical models, we discuss candidate neurotransmitter systems for study as targets for the treatment of binge eating. Dopaminergic circuits have been implicated in both laboratory animal models and human studies of binge eating, though existing medications specifically targeting the dopaminergic system have been found to have adverse side effects. Opioidergic and gamma-aminobutyric acid (GABA) systems also appear to be highly involved in aspects of binge eating; further, opioid antagonists, such as naloxone and naltrexone, and GABA agonists, such as baclofen, have all been shown to be effective in treating alcohol dependence and may be equally efficacious in attenuating binge eating. Preclinical evidence, and some clinical evidence, suggests that cannabinoid antagonism may also be useful in the treatment of binge eating, although the specific effect of antagonists, on binge consumption remains unclear. Overall, each of these neurotransmitter systems provides a promising avenue for new pharmacotherapy development for binge eating, and preclinical and human studies provide a strong rationale for the development of highly-selective drugs that target this neurocircuitry. PMID:21492094

  20. [LACTRIMS consensus document for the pharmacological treatment of the multiple sclerosis and its clinical variants].

    PubMed

    Abad, P; Nogales-Gaete, J; Rivera, V; Cristiano, E; Hamuy, F; Oehninger, C; Alvarenga, R M P; Tenembaum, S

    2012-12-16

    INTRODUCTION. Multiple sclerosis (MS) it is not considered any more a rare disease in Latin America. Most of the Latin American countries have reported moderate or lower prevalence data. However only very few countries have developed therapeutic guidelines. LACTRIMS prepared this consensus document with specific recommendations for the treatment of the disease. DEVELOPMENT. Experts on treatment and clinical research on MS were invited by LACTRIMS in order to generate a initial document to be discussed in Quito, Ecuador. Several groups were organized in relation of the different clinical variants. These groups were coordinated by experts leaders and prepared a preliminary document that was discussed in Quito during July 8th and 9th, 2011. Finally the final version was submitted to the members and delegates of LACTRIMS in most of the Latin American countries who were able to make modifications and suggest changes to the final manuscript. CONCLUSIONS. Based on the different evidence levels and the AGREE criteria, the clinical variants were reviewed and recommendations were made for the use of drugs and different modifying disease therapeutic agents. PMID:23233142

  1. Lacosamide as treatment for partial epilepsy: mechanisms of action, pharmacology, effects, and safety

    PubMed Central

    Kellinghaus, Christoph

    2009-01-01

    Lacosamide (LCM) is a novel agent that has been developed as an antiepileptic drug. In vitro studies suggest that LCM modulates voltage-gated sodium channels by enhancing their slow inactivation. In addition, LCM seems to interact with collapsin-response mediator protein 2 and thus may mediate neuronal plasticity. LCM has an elimination half-life of 13 hours, no relevant protein binding, and does not induce or inhibit enzymes of the cytochrome P450 system. No clinically significant drug–drug interactions have been discovered as yet. Experimental data suggest anticonvulsant as well as analgesic effects. Large clinical studies have demonstrated its efficacy for treatment of patients with partial seizures. LCM is well tolerated, and the most common adverse events are unspecific central nervous system and gastrointestinal effects such as dizziness, vertigo, nausea, and headache. LCM is approved for treatment of partial seizures with or without secondary generalization in the United States and the European Union within a dose range of 200 to 400 mg per day, administered twice daily. In addition to the oral formulations, an intravenous infusion solution is available. PMID:19816574

  2. Aerobic Exercise and Pharmacological Treatments Counteract Cachexia by Modulating Autophagy in Colon Cancer.

    PubMed

    Pigna, Eva; Berardi, Emanuele; Aulino, Paola; Rizzuto, Emanuele; Zampieri, Sandra; Carraro, Ugo; Kern, Helmut; Merigliano, Stefano; Gruppo, Mario; Mericskay, Mathias; Li, Zhenlin; Rocchi, Marco; Barone, Rosario; Macaluso, Filippo; Di Felice, Valentina; Adamo, Sergio; Coletti, Dario; Moresi, Viviana

    2016-01-01

    Recent studies have correlated physical activity with a better prognosis in cachectic patients, although the underlying mechanisms are not yet understood. In order to identify the pathways involved in the physical activity-mediated rescue of skeletal muscle mass and function, we investigated the effects of voluntary exercise on cachexia in colon carcinoma (C26)-bearing mice. Voluntary exercise prevented loss of muscle mass and function, ultimately increasing survival of C26-bearing mice. We found that the autophagic flux is overloaded in skeletal muscle of both colon carcinoma murine models and patients, but not in running C26-bearing mice, thus suggesting that exercise may release the autophagic flux and ultimately rescue muscle homeostasis. Treatment of C26-bearing mice with either AICAR or rapamycin, two drugs that trigger the autophagic flux, also rescued muscle mass and prevented atrogene induction. Similar effects were reproduced on myotubes in vitro, which displayed atrophy following exposure to C26-conditioned medium, a phenomenon that was rescued by AICAR or rapamycin treatment and relies on autophagosome-lysosome fusion (inhibited by chloroquine). Since AICAR, rapamycin and exercise equally affect the autophagic system and counteract cachexia, we believe autophagy-triggering drugs may be exploited to treat cachexia in conditions in which exercise cannot be prescribed. PMID:27244599

  3. Ziconotide: a review of its pharmacology and use in the treatment of pain

    PubMed Central

    McGivern, Joseph G

    2007-01-01

    Ziconotide is a powerful analgesic drug that has a unique mechanism of action involving potent and selective block of N-type calcium channels, which control neurotransmission at many synapses. The analgesic efficacy of ziconotide likely results from its ability to interrupt pain signaling at the level of the spinal cord. Ziconotide is a peptidic drug and has been approved for the treatment of severe chronic pain in patients only when administered by the intrathecal route. Importantly, prolonged administration of ziconotide does not lead to the development of addiction or tolerance. The current review discusses the various studies that have addressed the in vitro biochemical and electrophysiological actions of ziconotide as well as the numerous pre-clinical studies that were conducted to elucidate its antinociceptive mechanism of action in animals. In addition, this review considers the pivotal Phase 3 (and other) clinical trials that were conducted in support of ziconotide’s approval for the treatment of severe chronic pain and tries to offer some insights regarding the future discovery and development of newer analgesic drugs that would act by a similar mechanism to ziconotide but which might offer improved safety, tolerability and ease of use. PMID:19300539

  4. [Topical pharmacologic approach with 5% lidocaine medicated plaster in the treatment of localized neuropathic pain].

    PubMed

    Provinciali, L; Lattanzi, S; Chiarlone, R; Fogliardi, A; Intelligente, F; Irace, C; Lanzilotta, M; Palomba, R; Storelli, E; Zampi, M

    2014-12-01

    The treatment of neuropathic pain is a medical challenge. The responsiveness to the different classes of drugs is often unsatisfactory and frequently associated to a wide range of side effects. International guidelines suggest for the "localized" neuropathic pain the topical treatment with 5% lidocaine medicated plaster, alone or associated to systemic drugs, as the first choice since its favorable efficacy and tolerability profile. Many clinical experiences support the rationale for using 5% lidocaine medicated plaster in different kinds of localized neuropathic pain, such as postherpetic and trigeminal neuralgia, compressive syndromes, painful diabetic polyneuropathy and pain secondary to trauma or surgical interventions. This paper reports a series of clinical cases whose heterogeneity suggests the wide burden of applicability of the topical 5% lidocaine, either alone and associated to systemic drugs. All the described conditions were characterized by a highly intense pain, not adequately controlled by actual medications, which improved after the use of topical lidocaine. The good response to lidocaine allowed the reduction, of even the withdrawal, of concurrent drugs and improved the patients' quality of life. PMID:25392960

  5. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new.

    PubMed

    Eddleston, Michael; Chowdhury, Fazle Rabbi

    2016-03-01

    Despite being a major clinical and public health problem across the developing world, responsible for at least 5 million deaths over the last three decades, the clinical care of patients with organophosphorus (OP) insecticide poisoning has little improved over the last six decades. We are still using the same two antidotes - atropine and oximes - that first came into clinical use in the late 1950s. Clinical research in South Asia has shown how improved regimens of atropine can prevent deaths. However, we are still unsure about which patients are most likely to benefit from the use of oximes. Supplemental antidotes, such as magnesium, clonidine and sodium bicarbonate, have all been proposed and studied in small trials without production of definitive answers. Novel antidotes such as nicotinic receptor antagonists, beta-adrenergic agonists and lipid emulsions are being studied in large animal models and in pilot clinical trials. Hopefully, one or more of these affordable and already licensed antidotes will find their place in routine clinical care. However, the large number of chemically diverse OP insecticides, the varied poisoning they produce and their varied response to treatment might ultimately make it difficult to determine definitively whether these antidotes are truly effective. In addition, the toxicity of the varied solvents and surfactants formulated with the OP active ingredients complicates both treatment and studies. It is possible that the only effective way to reduce deaths from OP insecticide poisoning will be a steady reduction in their agricultural use worldwide. PMID:26366467

  6. Pharmacology of novel treatments for COPD: are fixed dose combination LABA/LAMA synergistic?

    PubMed

    Spina, Domenico

    2015-01-01

    Bronchodilators are mainstay for the symptomatic treatment of chronic obstructive pulmonary disease (COPD) and the introduction of long-acting bronchodilators has led to an improvement in the maintenance treatment of this disease. Various clinical trials have evaluated the effects of fixed dose long-acting β2-agonists (LABA)/long-acting anti-muscarinics (LAMA) combinations and documented greater improvements in spirometry but such improvements do not always translate to greater improvements in symptom scores or reduction in the rates of exacerbation compared with a single component drug. An analysis of whether this significantly greater change in spirometry with combination therapy is additive or synergistic was undertaken and is the subject of this review. Bronchodilators are not disease modifiers and whilst glucocorticosteroids have been shown to reduce rates of exacerbation in moderate to severe COPD, the increase risk of pneumonia and bone fractures is a motivation enough to warrant developing novel anti-inflammatory and disease-modifying drugs and with the expectation of positive outcomes. PMID:26557255

  7. Aerobic Exercise and Pharmacological Treatments Counteract Cachexia by Modulating Autophagy in Colon Cancer

    PubMed Central

    Pigna, Eva; Berardi, Emanuele; Aulino, Paola; Rizzuto, Emanuele; Zampieri, Sandra; Carraro, Ugo; Kern, Helmut; Merigliano, Stefano; Gruppo, Mario; Mericskay, Mathias; Li, Zhenlin; Rocchi, Marco; Barone, Rosario; Macaluso, Filippo; Di Felice, Valentina; Adamo, Sergio; Coletti, Dario; Moresi, Viviana

    2016-01-01

    Recent studies have correlated physical activity with a better prognosis in cachectic patients, although the underlying mechanisms are not yet understood. In order to identify the pathways involved in the physical activity-mediated rescue of skeletal muscle mass and function, we investigated the effects of voluntary exercise on cachexia in colon carcinoma (C26)-bearing mice. Voluntary exercise prevented loss of muscle mass and function, ultimately increasing survival of C26-bearing mice. We found that the autophagic flux is overloaded in skeletal muscle of both colon carcinoma murine models and patients, but not in running C26-bearing mice, thus suggesting that exercise may release the autophagic flux and ultimately rescue muscle homeostasis. Treatment of C26-bearing mice with either AICAR or rapamycin, two drugs that trigger the autophagic flux, also rescued muscle mass and prevented atrogene induction. Similar effects were reproduced on myotubes in vitro, which displayed atrophy following exposure to C26-conditioned medium, a phenomenon that was rescued by AICAR or rapamycin treatment and relies on autophagosome-lysosome fusion (inhibited by chloroquine). Since AICAR, rapamycin and exercise equally affect the autophagic system and counteract cachexia, we believe autophagy-triggering drugs may be exploited to treat cachexia in conditions in which exercise cannot be prescribed. PMID:27244599

  8. Oral pharmacological treatments for parasitic diseases of rainbow trout Oncorhynchus mykiss. II. Gyrodactylus sp.

    PubMed

    Tojo, J L; Santamarina, M T

    1998-07-30

    A total of 24 drugs were evaluated as regards their efficacy for oral treatment of gyrodactylosis in rainbow trout Oncorhynchus mykiss. In preliminary trials, all drugs were supplied to infected fish at 40 g per kg of feed for 10 d. Twenty-two of the drugs tested (aminosidine, amprolium, benznidazole, bithionol, chloroquine, diethylcarbamazine, flubendazole, levamisole, mebendazole, metronidazole, niclosamide, nitroxynil, oxibendazole, parbendazole, piperazine, praziquantel, ronidazole, secnidazole, tetramisole, thiophanate, toltrazuril and trichlorfon) were ineffective. Triclabendazole and nitroscanate completely eliminated the infection. Triclabendazole was effective only at the screening dosage (40 g per kg of feed for 10 d), while nitroscanate was effective at dosages as low as 0.6 g per kg of feed for 1 d. PMID:9745715

  9. [From symptomatic stability to functional recovery in the pharmacological treatment of schizophrenia and unipolar depression].

    PubMed

    Wikinski, Silvia

    2009-01-01

    This work summarizes the efficacy of pharmacotherapy in the chronic course of schizophrenia and unipolar depresion. It is aimed to answer three questions: does it cure these diseases? Does it exert any significant effect on the symptomatic presentation of the disorders? Which is its action on the social dysfunction provoked by schizophrenia or depression? A conceptual analysis of available bibliography was performed. It could be concluded that antypsychotics improve the symptomatic course of schizophrenia, although their efficacy is limited, and that these drugs does not act on the social dysfunction provoked by the disease. With respect to depression, it could be concluded that a significant proportion of patients remain symptomatic despite receiveng adequate treatments. No data about efficacy of pharmacotherapy on the dysfunction resultant from unipolar depression is available. PMID:20038986

  10. Rupatadine: pharmacological profile and its use in the treatment of allergic disorders.

    PubMed

    Picado, César

    2006-10-01

    Rupatadine is a once-daily, non-sedating, selective and long-acting new drug with a strong antagonist activity towards both histamine H(1) receptors and platelet-activating factor receptors. The use of rupatadine is indicated in adult and adolescent patients (> 12 years of age) suffering from intermittent and persistent allergic rhinitis and chronic idiopathic urticaria. In the treatment of these diseases, rupatadine is at least as effective as ebastine, cetirizine, loratadine and desloratadine. A very good safety profile of rupatadine has been evidenced in various studies, including a long-term (1-year) safety study. Rupatadine does not present drug-drug interactions with azithromycin, fluoxetine and lorazepam, but should not be administered concomitantly with known CYP3A4 inhibitors. PMID:17020424

  11. Rupatadine: pharmacological profile and its use in the treatment of allergic rhinitis.

    PubMed

    Sudhakara Rao, M; Dwarakanatha Reddy, D; Murthy, P S N

    2009-12-01

    Rupatadine is a once-daily, non-sedating, selective and long-acting new drug with a strong antagonist activity towards both histamine H1 receptors and platelet-activating factor receptors. The use of rupatadine is indicated in adult and adolescent patients (>12 years of age) suffering from intermittent and persistent allergic rhinitis. In the treatment of these conditions, rupatadine is at least as effective as ebastine, cetirizine, loratadine and desloratadine. Avery good safety profile of rupatadine has been evidenced in various studies, including a long-term (1-year) safety study. Rupatadine does not present drug-drug interactions with azithromycin, fluoxetine and lorazepam, but should not be administered concomitantly with known CYP3A4 inhibitors. PMID:23120659

  12. Progress on gene therapy, cell therapy, and pharmacological strategies toward the treatment of oculopharyngeal muscular dystrophy.

    PubMed

    Harish, Pradeep; Malerba, Alberto; Dickson, George; Bachtarzi, Houria

    2015-05-01

    Oculopharyngeal muscular dystrophy (OPMD) is a muscle-specific, late-onset degenerative disorder whereby muscles of the eyes (causing ptosis), throat (leading to dysphagia), and limbs (causing proximal limb weakness) are mostly affected. The disease is characterized by a mutation in the poly(A)-binding protein nuclear-1 (PABPN1) gene, resulting in a short GCG expansion in the polyalanine tract of PABPN1 protein. Accumulation of filamentous intranuclear inclusions in affected skeletal muscle cells constitutes the pathological hallmark of OPMD. This review highlights the current translational research advances in the treatment of OPMD. In vitro and in vivo disease models are described. Conventional and experimental therapeutic approaches are discussed with emphasis on novel molecular therapies including the use of intrabodies, gene therapy, and myoblast transfer therapy. PMID:25860803

  13. Cancer Stem and Progenitor-Like Cells as Pharmacological Targets in Breast Cancer Treatment

    PubMed Central

    de Souza, Valéria B.; Schenka, André A.

    2015-01-01

    The present review is focused on the current role of neoplastic stem and progenitor-like cells as primary targets in the pharmacotherapy of cancer as well as in the development of new anticancer drugs. We begin by summarizing the main characteristics of these tumor-initiating cells and key concepts that support their participation in therapeutic failure. In particular, we discuss the differences between the major carcinogenesis models (ie, clonal evolution vs cancer stem cell (CSC) model) with emphasis on breast cancer (given its importance to the study of CSCs) and their implications for the development of new treatment strategies. In addition, we describe the main ways to target these cells, including the main signaling pathways that are more activated or altered in CSCs. Finally, we provide a comprehensive compilation of the most recently tested drugs. PMID:26609237

  14. Scientific Evaluation of Pharmacological Treatment of Osteoarthritis in the Canon of Medicine.

    PubMed

    Choopani, Rasool; Ghourchian, Anahita; Hajimehdipoor, Homa; Kamalinejad, Mohammad

    2016-07-01

    Osteoarthritis is the most common articular disease worldwide. Nonetheless, common osteoarthritis treatments are either not effective or associated with side effects. Now the materials derived from plants have found a relevant place in drug discovery. Until the mid-18th century, osteoarthritis in all medical schools worldwide had been managed as general arthritis. Avicenna, the famous scholar of Iranian traditional medicine has provided a long list of herbs that have been used traditionally to treat arthritis. To gain this worthy list, we searched his most famous medical masterpiece: Canon of Medicine Some of these materials are investigated and employed by modern medicine. However, it is difficult to ignore that still more of these naturally occurring materials could be of use in modern medicine not only to prevent osteoarthritis progression but also osteoarthritis management as natural anti-inflammatory drugs. PMID:26311572

  15. [Long-term outcome of pharmacological and nonpharmacological treatment for ventricular arrhythmias].

    PubMed

    Ohnishi, S; Kasanuki, H

    2000-03-01

    Recent advances of nonpharmacological therapy such as catheter ablation and implantable cardioverter defibrillator and lessons from the Cardiac Arrhythmia Suppression Trial(CAST) have changed the strategy for ventricular arrhythmias. The safety and efficacy of radiofrequency catheter ablation of symptomatic sustained monomorphic ventricular tachycardia without structural heart disease has made ablation the firstline curative therapy. In idiopathic ventricular fibrillation such as Brugada syndrome, an implantable cardioverter defibrillator is the most effective treatment to prevent sudden cardiac death. In patients with asymptomatic ventricular tachyarrhythmias in heart failure, class I antiarrhythmic drugs should be avoided due to proarrhythmic and negative inotropic effects that may be responsible for increased mortality in some trials. In such patients, amiodarone and beta-blocker may reduce sudden cardiac death. For patients with sustained ventricular tachycardia or ventricular fibrillation in heart failure, amiodarone or implantable cardioverter defibrillator should be considered. In comparison with amiodarone, implantable cardioverter defibrillator markedly reduced sudden death in ventricular tachycardia and ventricular fibrillation survivors in Antiarrhythmics Versus Implantable Defibriltors(AVID). Although better patient selection and clarification of mapping criteria improved the successful ablation rate in patients with structural heart disease, candidates of ablation are few. In patients with extensive structural heart disease, multiple ventricular tachycardias are often present. Catheter ablation of a single ventricular tachycardia may be only palliative. Therefore, implantable cardioverter defibrillator is the most effective treatment to prevent sudden cardiac death, with amiodarone and ablation as the adjunctive therapy to prevent frequent ventricular tachycardia. Furthermore, an implantable cardioverter defibrillator improved survival in selected

  16. Prevalence and Pharmacologic Treatment of Patients with Low Back Pain Treated at Kosovo Energetic Corporation

    PubMed Central

    Ibraimi, Zana; Murtezani, Ardiana; Haxhiu, Bekim; Mustafa, Aziz; Martinaj, Merita

    2013-01-01

    ABSTRACT Introduction: Low back pain (LBP) is a common complaint among the general population with a subgroup developing chronic and disabling symptoms generating large societal costs. Recurrences and functional limitations can be minimized with appropriate conservative management, including medications, physical therapy modalities, exercise and patient education. Objectives: The purpose of this study was to determine the prevalence of low back complaints in industrial workers, to investigate whether individual risk factors involved in the occurrence of LBP, and to determine the most frequent used drug in LBP treatment. Materials and Methods: Data for this study were provided from Kosovo Energetic Corporation. A cross-sectional study design was utilized. Self-administered questionnaires were distributed among 228 industrial workers. Patient with LBP underwent a comprehensive clinical, radiological and biochemical evaluation. Results: showed that LBP occurred in 63.5% of workers. Individual factors did not show significant associations with LBP. Age (OR=0.99/95% Cl 0.95-1.03), weight (OR=1.13/95% Cl 0.99-1.06), height (OR=0.97/95% Cl 0.91-1.02), and work experience (OR=1.01/95% Cl 0.97-1.05) increase odds for LBP but not significantly. The most frequently used drugs in patients included in this study are NSAIDs. In 33 (55.0%) patients for the treatment of LBP two types of drugs are administered. Conclusion: Increased physical activity, health promotion and reduced body weight can prevent morbidity from LBP. A continuous consultation with the Clinical Pharmacist demonstrates effective way of dosage and drug re-evaluation for the patients with LBP. PMID:25568510

  17. Pharmacological Characterization of ZYAN1, a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia.

    PubMed

    Jain, M R; Joharapurkar, A A; Pandya, V; Patel, V; Joshi, J; Kshirsagar, S; Patel, K; Patel, P R; Desai, R C

    2016-02-01

    Prolyl hydroxylase (PHD) inhibitors stabilize hypoxia inducible factor (HIF), and exert antianemic effect by potentiating erythropoietin (EPO) expression and down-regulation of hepcidin. ZYAN1 is a novel PHD inhibitor under clinical development for the treatment of anemia. The pharmacodynamic effects of acute and chronic dosing of ZYAN1 were assessed in normal and 5/6 nephrectomized Wistar rats. The effect of ZYAN1 was also investigated in cisplatin-induced anemia using C57 mice. Acute treatment with ZYAN1 increased circulating EPO levels (10.3±3.7 and 40.0±8.5 fold rise at 15 and 30 mg/kg, respectively), reticulocyte count (4.2±0.5 and 6.0±0.2 fold rise at 15 and 30 mg/kg, respectively) and stabilized HIF (28% increase at 45 mg/kg) in normal rats. Nephrectomized rats showed similar dose-related pharmacodynamic effects. In a 28-day study in nephrectomized rats, ZYAN1 administered every alternate day, caused increase in hemoglobin (1.9±0.3 and 2.5±0.4 g/dL) and RBC count (10.7±4.0 and 14.0±4.1%) at 15 and 30 mg/kg respectively. In cisplatin-treated mice also an increase in hemoglobin (3.4±0.2 and 5.9±0.2 g/dL) and RBC count (22.5±2.2 and 37.3±1.7%) at 15 and 30 mg/kg respectively was observed. ZYAN1's effects on hemoglobin and RBC count were distinct from darbepoietin. ZYAN1 demonstrated hematinic potential by combined effects on EPO release and efficient iron utilization. The efficacy of ZYAN1 in disease models of different etiologies suggests that it will be useful in treating wide spectrum of anemia patients. PMID:26367279

  18. Pharmacological treatment and prevention of cerebral small vessel disease: a review of potential interventions

    PubMed Central

    Wardlaw, Joanna M.

    2015-01-01

    Small vessel disease encompasses lacunar stroke, white matter hyperintensities, lacunes and microbleeds. It causes a quarter of all ischemic strokes, is the commonest cause of vascular dementia, and the cause is incompletely understood. Vascular prophylaxis, as appropriate for large artery disease and cardioembolism, includes antithrombotics, and blood pressure and lipid lowering; however, these strategies may not be effective for small vessel disease, or are already used routinely so precluding further detailed study. Further, intensive antiplatelet therapy is known to be hazardous in small vessel disease through enhanced bleeding. Whether acetylcholinesterase inhibitors, which delay the progression of Alzheimer's dementia, are relevant in small vessel disease remains unclear. Potential prophylactic and treatment strategies might be those that target brain microvascular endothelium and the blood brain barrier, microvascular function and neuroinflammation. Potential interventions include endothelin antagonists, neurotrophins, nitric oxide donors and phosphodiesterase 5 inhibitors, peroxisome proliferator‐activated receptor‐gamma agonists, and prostacyclin mimics and phosphodiesterase 3 inhibitors. Several drugs that have relevant properties are licensed for other disorders, offering the possibility of drug repurposing. Others are in development. Since influencing multiple targets may be most effective, using multiple agents and/or those that have multiple effects may be preferable. We focus on potential small vessel disease mechanistic targets, summarize drugs that have relevant actions, and review data available from randomized trials on their actions and on the available evidence for their use in lacunar stroke. PMID:25727737

  19. Pharmacology and metabolism of infliximab biosimilars - A new treatment option in inflammatory bowel diseases.

    PubMed

    Włodarczyk, Marcin; Fichna, Jakub; Sobolewska-Włodarczyk, Aleksandra

    2016-08-01

    Biological therapy with monoclonal antibodies to tumor necrosis factor alpha (TNF-α) was shown in large clinical trials to be effective in inducing and maintaining clinical remission in patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). Infliximab, the first anti-TNF-α biologic drug, has significantly improved inflammatory bowel disease (IBD) treatment outcomes by preventing structural damage progression, thereby reducing complications and the need for surgery and hospitalization. The major concern associated with the use of biologics is their high cost. However, as these therapies lose patent protection, cheaper biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT-P13. Position statements from several scientific societies and some experts in their reviews have expressed concerns to the concept of extrapolation without direct IBD clinical evidence, whereas European Medicines Agency (EMA) experts have supported extrapolation. In this review, we focus on the pharmacokinetics, pharmacodynamics properties and comparative effectiveness of anti-TNF-α biosimilars, related to their use in IBD. PMID:27162107

  20. Prevention and Treatment of Type 2 Diabetes: Current Role of Lifestyle, Natural Product, and Pharmacological Interventions

    PubMed Central

    Hays, Nicholas P.; Galassetti, Pietro R.; Coker, Robert H.

    2008-01-01

    Common complications of Type 2 diabetes (T2D) are eye, kidney and nerve diseases, as well as an increased risk for the development of cardiovascular disease and cancer. The overwhelming influence of these conditions contributes to a decreased quality of life and life span, as well as significant economic consequences. Although obesity once served as a surrogate marker for the risk of T2D, we know now that excess adipose tissue secretes inflammatory cytokines that left unchecked, accelerate the progression to insulin resistance and T2D. In addition, excess alcohol consumption may also increase the risk of T2D. From a therapeutic standpoint, lifestyle interventions such as dietary modification and/or exercise training have been shown to improve glucose homeostasis but may not normalize the disease process unless weight loss is achieved and increased physical activity patterns are established. Furthermore, utilization of natural products may serve as a significant adjunct in the fight against insulin resistance but further research is needed to ascertain their validity. Since it is clear that pharmaceutical therapy plays a significant role in the treatment of insulin resistance, this review will also discuss some of the newly developed pharmaceutical therapies that may work in conjunction with lifestyle interventions, and lessen the burden of behavioral change as the only strategy against the development of T2D. PMID:18423879

  1. Pharmacological Treatment of Idiopathic Pulmonary Fibrosis: Current Approaches, Unsolved Issues, and Future Perspectives

    PubMed Central

    Kreuter, Michael; Bonella, Francesco; Wijsenbeek, Marlies; Maher, Toby M.; Spagnolo, Paolo

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating condition with a 5-year survival of approximately 20%. The disease primarily occurs in elderly patients. IPF is a highly heterogeneous disorder with a clinical course that varies from prolonged periods of stability to episodes of rapid deterioration. In the last decade, improved understanding of disease mechanisms along with a more precise disease definition has allowed the design and completion of a number of high-quality clinical trials. Yet, until recently, IPF was essentially an untreatable disease. Finally, pirfenidone and nintedanib, two compounds with antifibrotic properties, have consistently proven effective in reducing functional decline and disease progression in IPF. This is a major breakthrough for patients and physicians alike, but there is still a long way to go. In fact, neither pirfenidone nor nintedanib is a cure for IPF, and most patients continue to progress despite treatment. As such, comprehensive care of patients with IPF, including management of comorbidities/complications and physical debility and timely referral for palliative care or, in a small number of highly selected patients, lung transplantation, remains essential. Several agents with high potential are currently being tested and many more are ready to be evaluated in clinical trials. PMID:26779535

  2. Pharmacology and clinical potential of vortioxetine in the treatment of major depressive disorder

    PubMed Central

    Alvarez, Enric; Perez, Victor; Artigas, Francesc

    2014-01-01

    Vortioxetine is a new multimodal action antidepressant with two types of action: serotonin transporter (SERT) blockade and a strong affinity for several serotoninergic receptors. It is an antagonist of the 5-HT3 and 5-HT7 receptors, a partial agonist of 5-HT1B, and an agonist of 5-HT1A. Its combined action on SERT and four subtypes of serotoninergic receptors increases the extracellular concentration of serotonin, dopamine, and noradrenaline. Twelve clinical trials have been carried out, nine of which had positive results versus placebo. When active comparators were included in the study design, no significant differences were found except in one study in which the efficacy of vortioxetine was superior to the comparator (agomelatine) in depression resistant to selective serotonin reuptake inhibitors (SSRI)/serotonin–norepinephrine reuptake inhibitors (SNRI) treatment. Tolerability studies indicate that the drug does not cause any important problems on blood tests, vital signs, or on electrocardiography. The lack of weight gain and induction of metabolic syndrome and the lack of significant changes in the QTc are especially important. The incidence rate of sexual dysfunction is low and similar to placebo in various trials. Similarly, cognitive function remains intact with vortioxetine. PMID:25075188

  3. The clinical pharmacology of therapeutic monoclonal antibodies in the treatment of malignancy; have the magic bullets arrived?

    PubMed Central

    Newsome, Barrett W; Ernstoff, Marc S

    2008-01-01

    Monoclonal antibodies (Mabs) are proteins in the immunoglobulin family that bind to specific protein epitope targets on cancer and stromal cells, allowing them to be successfully exploited as therapeutic agents. The prototype Mabs were produced from fusion of mouse B lymphocytes and mouse myeloma cells and were entirely murine in sequence. Subsequent advances in technology have allowed for humanized Mabs, which have different pharmacokinetic properties than murine Mabs in humans. Mabs antitumour activity is mediated through direct interaction with specific target molecules, deployment of immune cytotoxic pathways, or through chaperoning cytotoxic agents to tumour. Mabs are typically administered intravenously, are generally well tolerated and can have powerful anticancer activity. Humanized Mabs have a t1/2 in human sera of 2–3 weeks, which determines the frequency of administration. At present, nine clinically approved Mabs are used in the treatment of human cancer, and many others are in clinical trials. We discuss the pharmacology, clinical indications, and toxicity of the currently available anticancer Mabs in this review. PMID:18503606

  4. Genetic and pharmacological targeting of TPL-2 kinase ameliorates experimental colitis: a potential target for the treatment of Crohn's disease?

    PubMed

    Lawrenz, M; Visekruna, A; Kühl, A; Schmidt, N; Kaufmann, S H E; Steinhoff, U

    2012-03-01

    Inflammatory bowel disease is characterized by dysregulated immune responses against intestinal microflora leading to marked activation of nuclear factor-κB (NF-κB) with subsequent production of pro-inflammatory cytokines. Besides NF-κB, the tumor progression locus 2 (TPL-2)/extracellular signal-regulated kinase (ERK) pathway also regulates inflammatory cytokines such as interleukin-1β and tumor necrosis factor-α, but its role during intestinal inflammation is incompletely understood. We analyzed the impact of TPL-2 in the dextran sulfate sodium-induced experimental colitis model. Despite normal activation of NF-κB, animals lacking TPL-2 developed only mild colitis with reduced synthesis of inflammatory cytokines. Further, pharmacological inhibition of the TPL-2 kinase was similarly effective in ameliorating colitis as TPL-2 deficiency without obvious side effects. Because increased TPL-2/ERK activation was seen in patients with Crohn's disease (CD) but not ulcerative colitis, our findings encourage further investigation of TPL-2 kinase as potential target for the treatment of CD patients. PMID:22157885

  5. Pharmacological Treatment of Alzheimer’s Disease: Is it Progressing Adequately?

    PubMed Central

    Robles, Alfredo

    2009-01-01

    Introduction: Between 1993 and 2000 four acetylcholinesterase inhibitors were marketed as a symptomatic treatment for Alzheimer’s disease (AD), as well as memantine in 2003. Current research is focused on finding drugs that favorably modify the course of the disease. However, their entrance into the market does not seem to be imminent. Research Development: The aim of AD research is to find substances that inhibit certain elements of the AD pathogenic chain (beta- and gamma-secretase inhibitors, alpha-secretase stimulants, beta-amyloid aggregability reducers or disaggregation and elimination inductors, as well as tau-hyperphosphorylation, glutamate excitotoxicity, oxidative stress and mitochondrial damage reducers, among other action mechanisms). Demonstrating a disease’s retarding effect demands longer trials than those necessary to ascertain symptomatic improvement. Besides, a high number of patients (thousands of them) is necessary, all of which turns out to be difficult and costly. Furthermore, it would be necessary to count on diagnosis and progression markers in the disease’s pre-clinical stage, markers for specific phenotypes, as well as high-selectivity molecules acting only where necessary. In order to compensate these difficulties, drugs acting on several defects of the pathogenic chain or showing both symptomatic and neuroprotective action simultaneously are being researched. Conclusions: There are multiple molecules used in research to modify AD progression. Although it turns out to be difficult to obtain drugs with sufficient efficacy so that their marketing is approved, if they were achieved they would lead to a reduction of AD prevalence. PMID:19461897

  6. A review of phytotherapy of gout: perspective of new pharmacological treatments.

    PubMed

    Ling, X; Bochu, W

    2014-04-01

    The purpose of this review article is to outline plants currently used and those with high promise for the development of anti-gout products. All relevant literature databases were searched up to 25 March 2013. The search terms were 'gout', 'gouty arthritis', 'hyperuricemia', 'uric acid', 'xanthine oxidase (XO) inhibitor', 'uricosuric', 'urate transporter 1(URAT1)' and 'glucose transporter 9 (GLUT9)'. Herbal keywords included 'herbal medicine', 'medicinal plant', 'natural products', 'phytomedicine' and 'phytotherapy'. 'antiinflammatory effect' combined with the words 'interleukin-6 (IL-6)', 'interleukin-8 (IL-8)', 'interleukin-1beta (IL-1beta)', and 'tumor necrosis factor alpha (TNF-alpha)'. XO inhibitory effect, uricosuric action, and anti-inflammatory effects were the key outcomes. Numerous agents derived from plants have anti-gout potential. In in vitro studies, flavonoids, alkaloids, essential oils, phenolic compounds, tannins, iridoid glucosides, and coumarins show the potential of anti-gout effects by their XO inhibitory action, while lignans, triterpenoids and xanthophyll are acting through their anti-inflammatory effects. In animal studies, essential oils, lignans, and tannins show dual effects including reduction of uric acid generation and uricosuric action. Alkaloids reveal inhibit uric acid generation, show anti-inflammatory effects, or a combination of the two. Phenolic compounds and flavonoids inhibit uric acid production, show uricosuric anti-inflammatory effects. In the rare human studies, colchicine from Colchicum autumnale showed anti-inflammatory effects while for other plant extracts, although revealing anti-gout potential, further phytochemical investigations are needed to identify their active constituents. Besides, the plants which give antioxidant activities are much potent in the management of gout and need to be further investigated. The current review is a detailed discussion of the potential of medicinal plants for treatment of gout

  7. Novel treatment of acute promyelocytic leukemia: As₂O₃, retinoic acid and retinoid pharmacology.

    PubMed

    Zhu, George; Mische, Sarah E; Seigneres, Beatrice

    2013-01-01

    Acute promyelocytic leukemia(APL), a specific characteristic of t(15;17) chromosome translocation, represents 5% to 15% of cases of acute nonlymphocytic leukemia. An alternative approach is to consider retinoic acid(all-trans RA, ATRA or 13-cis RA or 9-cis RA) plus chemotherapy or RA plus As₂O₃ regimens as now novel therapy. Molecular gene analyses are conclusive in vivo evidence that oncogenic PML/RARa plays a crucial role in APL leukemogenesis. As a novel approach to APL treatment, one possible the action of RA, A consense sequence (5'-TCAGGTCATGACCTGA-3') has been postulated for the thyroid hormone (TRE) and retinoic acid responsive element (RARE) containing half palindromes, which located in the promoter region of target genes. High dose (100-fold) of RA-RARE-PML/RARa complex in intracellular localization appears to relieve repressor from DNA binding, including corepressors N-CoR, SMRT and HDACs, release PML/RARa- mediated transcriptional repression, and release histone deacetylase activity from PMLRARa. The resulting PML/RARa oncoprotein proteolytic degradation through the autophagy-lysosome pathway and the ubiquitin SUMO-proteasome system (UPS), as well as caspase 3 (cleavage site Asp522 within a-helics region of PML component of the fusion protein) or neutrophil elastase, or lysosomal protease enzyme induction. PML protein relocalizes into the wild-type nuclear body (PML-NB) configuration or/and wild-type RARa upregulated. An effect to relieve the blockade (inhibition) of PML/RARA-mediated RA dependent promyelocytic differentiation, and retinoic acid in APL therapy (see Figure in the full text, George Zhu, 1991). Here, like v-erbA, PML/RARa is a (strong) transcriptional repressor of the RA receptor (RAR) complex, and PML/RARa fusion receptor gene act as conditional oncogenic receptor (translocated chimeric retinoic acid a signaling) or oncogenic PML/RARa may participate in leukemogenesis of APL through blocking RA-mediated promyelocytic differentiation

  8. Pharmacological Analysis of Vorinostat Analogues as Potential Anti-tumor Agents Targeting Human Histone Deacetylases: an Epigenetic Treatment Stratagem for Cancers.

    PubMed

    Praseetha, Sugathan; Bandaru, Srinivas; Nayarisseri, Anuraj; Sureshkumar, Sivanpillai

    2016-01-01

    Alteration of the acetylation status of chromatin and other non-histone proteins by HDAC inhibitors has evolved as an excellent epigenetic strategy in treatment of cancers. The present study was sought to identify compounds with positive pharmacological profiles targeting HDAC1. Analogues of Vorinostat synthesized by Cai et al, 2015 formed the test compounds for the present pharmacological evaluation. Hydroxamte analogue 6H showed superior pharmacological profile in comparison to all the compounds in the analogue dataset owing to its better electrostatic interactions and hydrogen bonding patterns. In order to identify compounds with even better high affinity and pharmacological profile than 6H and Vorinostat, virtual screening was performed. A total of 83 compounds similar to Vorinostat and 154 compounds akin to analogue 6H were retrieved. SCHEMBL15675695 (PubCid: 15739209) and AKOS019005527 (PubCid: 80442147) similar to Vorinostat and 6H, were the best docked compounds among the virtually screened compounds. However, in spite of having good affinity, none of the virtually screened compounds had better affinity than that of 6H. In addition SCHEMBL15675695 was predicted to be a carcinogen while AKOS019005527 is Ames toxic. From, our extensive analysis involving binding affinity analysis, ADMET properties predictions and pharmacophoric mappings, we report Vorinostat hydroxamate analogue 6H to be a potential candidate for HDAC inhibition in treatment of cancers through an epigenetic strategy. PMID:27039807

  9. Optimal individualized dosing strategies: A pharmacologic approach to developing dynamic treatment regimens for continuous-valued treatments.

    PubMed

    Rich, Benjamin; Moodie, Erica E M; Stephens, David A

    2016-05-01

    There have been considerable advances in the methodology for estimating dynamic treatment regimens, and for the design of sequential trials that can be used to collect unconfounded data to inform such regimens. However, relatively little attention has been paid to how such methodology could be used to advance understanding of optimal treatment strategies in a continuous dose setting, even though it is often the case that considerable patient heterogeneity in drug response along with a narrow therapeutic window may necessitate the tailoring of dosing over time. Such is the case with warfarin, a common oral anticoagulant. We propose novel, realistic simulation models based on pharmacokinetic-pharmacodynamic properties of the drug that can be used to evaluate potentially optimal dosing strategies. Our results suggest that this methodology can lead to a dosing strategy that performs well both within and across populations with different pharmacokinetic characteristics, and may assist in the design of randomized trials by narrowing the list of potential dosing strategies to those which are most promising. PMID:26537297

  10. Getting better, getting well: understanding and managing partial and non-response to pharmacological treatment of non-psychotic major depression in old age.

    PubMed

    Driscoll, Henry C; Karp, Jordan F; Dew, Mary Amanda; Reynolds, Charles F

    2007-01-01

    In general, the pharmacological treatment of non-psychotic major depressive disorder in old age is only partially successful, with only approximately 50% of older depressed adults improving with initial antidepressant monotherapy. Many factors may predict a more difficult-to-treat depression, including coexisting anxiety, low self-esteem, poor sleep and a high coexisting medical burden. Being aware of these and other predictors of a difficult-to-treat depression gives the clinician more reasonable expectations about a patient's likely treatment course. If an initial antidepressant trial fails, the clinician has two pharmacological options: switch or augment/combine antidepressant therapies. About 50% of patients who do not improve after initial antidepressant therapy will respond to either strategy. Switching has several advantages including fewer adverse effects, improved treatment adherence and reduced expense. However, as a general guideline, if patients are partial responders at 6 weeks, they will likely be full responders by 12 weeks. Thus, changing medication is not indicated in this context. However, if patients are partial responders at 12 weeks, switching to a new agent is advised. If the clinician treats vigorously and if the patient and clinician persevere, up to 90% of older depressed patients will respond to pharmacological treatment. Furthermore, electroconvulsive therapy is a safe and effective non-pharmacological strategy for non-psychotic major depression that fails to respond to pharmacotherapy. Getting well and staying well is the goal; thus, clinicians should treat to remission, not merely to response. Subsequently, maintenance treatment with the same regimen that has been successful in relieving the depression strongly improves the patient's chances of remaining depression free. PMID:17896830

  11. A network pharmacology approach to discover active compounds and action mechanisms of San-Cao Granule for treatment of liver fibrosis

    PubMed Central

    Wei, Shizhang; Niu, Ming; Wang, Jian; Wang, Jiabo; Su, Haibin; Luo, Shengqiang; Zhang, Xiaomei; Guo, Yanlei; Liu, Liping; Liu, Fengqun; Zhao, Qingguo; Chen, Hongge; Xiao, Xiaohe; Zhao, Pan; Zhao, Yanling

    2016-01-01

    Ethnopharmacological relevance San-Cao Granule (SCG) has been used in patients with liver fibrosis for many years and has shown good effect. However, its mechanism of therapeutic action is not clear because of its complex chemical system. The purpose of our study is to establish a comprehensive and systemic method that can predict the mechanism of action of SCG in antihepatic fibrosis. Materials and methods In this study, a “compound–target–disease” network was constructed by combining the SCG-specific and liver fibrosis–specific target proteins with protein–protein interactions, and network pharmacology was used to screen out the underlying targets and mechanisms of SCG for treatment of liver fibrosis. Then, some key molecules of the enriched pathway were chosen to verify the effects of SCG on liver fibrosis induced by thioacetamide (TAA). Results This systematic approach had successfully revealed that 16 targets related to 11 SCG compounds were closely associated with liver fibrosis therapy. The pathway-enrichment analysis of them showed that the TGF-β1/Smad signaling pathway is relatively important. Animal experiments also proved that SCG could significantly ameliorate liver fibrosis by inhibiting the TGF-β1/Smad pathway. Conclusion SCG could alleviate liver fibrosis through the molecular mechanisms predicted by network pharmacology. Furthermore, network pharmacology could provide deep insight into the pharmacological mechanisms of Chinese herbal formulas. PMID:26929602

  12. Protons, Photons, and the Prostate – Is There Emerging Evidence in the Ongoing Discussion on Particle Therapy for the Treatment of Prostate Cancer?

    PubMed Central

    Schiller, Kilian C.; Habl, Gregor; Combs, Stephanie E.

    2016-01-01

    Proton therapy is actively and repeatedly discussed within the framework of particle therapy for the treatment of prostate cancer (PC). The argument in favor of treating the prostate with protons is partly financial: given that small volumes are treated, treatment times are low, resulting in a hypothetical high patient throughput. However, such considerations should not form the basis of medical decision-making. There are also physical and biological arguments which further support the use of particle therapy for PC. The only relevant randomized data currently available is the study by Zietman and colleagues, comparing a high to a low proton boost, resulting in a significant increase in PSA-free survival in the experimental (high dose) arm (1). With modern photon treatments and image-guided radiotherapy (IGRT), equally high doses can be applied with photons and, thus, a randomized trial comparing high-end photons to protons is warranted. For high-linear energy transfer (LET) particles, such as carbon ions, the increase in relative biological effectiveness could potentially convert into an improvement in outcome. Additionally, through the physical differences of protons and carbon ions, the steeper dose gradient with carbon ions and the lack of beam broadening in the carbon beam lead to a superior dose distribution supporting the idea of hypofractionation. Biological and clinical data are emerging, however, has practice-changing evidence already arrived? PMID:26858936

  13. Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction

    PubMed Central

    Kong, Qingxia; Min, Xia; Sun, Ran; Gao, Jianying; Liang, Ruqing; Li, Lei; Chu, Xu

    2016-01-01

    The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented

  14. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders - first revision.

    PubMed

    Bandelow, Borwin; Zohar, Joseph; Hollander, Eric; Kasper, Siegfried; Möller, Hans-Jürgen; Zohar, Joseph; Hollander, Eric; Kasper, Siegfried; Möller, Hans-Jürgen; Bandelow, Borwin; Allgulander, Christer; Ayuso-Gutierrez, José; Baldwin, David S; Buenvicius, Robertas; Cassano, Giovanni; Fineberg, Naomi; Gabriels, Loes; Hindmarch, Ian; Kaiya, Hisanobu; Klein, Donald F; Lader, Malcolm; Lecrubier, Yves; Lépine, Jean-Pierre; Liebowitz, Michael R; Lopez-Ibor, Juan José; Marazziti, Donatella; Miguel, Euripedes C; Oh, Kang Seob; Preter, Maurice; Rupprecht, Rainer; Sato, Mitsumoto; Starcevic, Vladan; Stein, Dan J; van Ameringen, Michael; Vega, Johann

    2008-01-01

    In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines. PMID:18949648

  15. On the Occasion of World Cancer Day 2015; the Possibility of Cancer Prevention or Treatment with Antioxidants: The Ongoing Cancer Prevention Researches

    PubMed Central

    Rafieian-Kopaie, Mahmoud; Nasri, Hamid

    2015-01-01

    On February, 2014 World Cancer Day (WCD) was established to raise alertness of cancer and to encourage its prevention, detection, and treatment. In fact, WCD is celebrated every year on the 4th of February all over the world to commemorate all the accomplishments of the WHO. In this paper, we aimed to present the scientific evidence for the role of antioxidants in cancer. Damage to cells by reactive oxygen species, especially the damage to DNA, has been found to play a crucial role in the development of cancer. Exogenous antioxidants can prevent free radical damage associated with cancer development. However, whether or not taking dietary antioxidants can prevent or reduce the risk of developing cancer in humans is not clear. Some researchers have suggested that antioxidants counteract with drugs or toxins, which induce oxidative stress and hence prevent damage to cells or body organs. PMID:26644907

  16. To Sleep or Not To Sleep: A Systematic Review of the Literature of Pharmacological Treatments of Insomnia in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Barrett, Jessica R.; Tracy, Derek K.

    2013-01-01

    Abstract Objective: This systematic review assessed current evidence on sleep medication for attention-deficit/hyperactivity disorder (ADHD) patients, to establish appropriate guidance for clinicians faced with prescribing such medications. Methods: Five articles (based on four pharmacological compounds) out of a total 337 were identified as evidence to guide pharmacological treatment of ADHD-related sleep disorders. Data regarding participant characteristics, measures of ADHD diagnosis, measures of sleep, and outcome data were extracted. Results: Zolpidem and L-theanine both displayed a poor response in reducing sleep latency and increasing total sleep time, however L-theanine did produce an increase in sleep efficiency. Zolpidem produced high levels of side effects, leading to the largest dropout rate of all five studies. Clonidine reduced insomnia; and melatonin also exhibited a positive response, with reduced sleep latency, higher total sleep time, and higher sleep efficiency. Conclusions: There is a relative paucity of evidence for the pharmacological treatment of ADHD-related sleep disorders; therefore, further research should be conducted to replicate these findings and obtain reliable results. PMID:24261659

  17. Metabolomics Profiling to Investigate the Pharmacologic Mechanisms of Berberine for the Treatment of High-Fat Diet-Induced Nonalcoholic Steatohepatitis

    PubMed Central

    Li, Jian; Liu, Zezhou; Xu, Kejia; Jiang, Miao; Lu, Aiping; Gao, Xiaoyan

    2015-01-01

    Objective. Berberine has been used to treat nonalcoholic steatohepatitis (NASH), which has been addressed in many studies. In this study, we investigated the molecular pharmacology mechanisms of berberine using metabolomic techniques. Methods. Sprague-Dawley rats were randomly divided into three groups (10 rats in each group): (i) normal control group; (ii) high-fat diet- (HFD-) induced NASH model group; and (iii) HFD berberine-treated group (i.d. 200 mg/kg). The handling procedure lasted eight weeks. Then, UPLC-Q-TOF/MS techniques coupled with histopathology and biochemical analyses were adopted to explore the mechanisms of berberine on the protective effects against NASH. Key Findings. (i) According to conventional test results, berberine treatment plays a fighting role in HFD-induced NASH due to its beneficial effects against insulin resistance, inflammation, and lipid metabolism. (ii) Based on UPLC-Q-TOF/MS techniques, metabolic profiles that involved sphingomyelin (SM), phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), 13-hydroperoxy-9, 11-octadecadienoic acid (13-HpODE), eicosatrienoic acid, docosatrienoic acid, and eicosenoic acid could provide potential metabolic biomarkers to address the pharmacological mechanisms of berberine. Conclusions. The parts of molecular pharmacological mechanisms of berberine for NASH treatment are related to the regulation of metabolic disruption involving phospholipid and unsaturated fatty acids in rats with NASH. PMID:25977701

  18. Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease

    PubMed Central

    Li, Jiansheng; Zhao, Peng; Li, Ya; Tian, Yange; Wang, Yonghua

    2015-01-01

    The present work adopted a systems pharmacology-based approach to provide new insights into the active compounds and therapeutic targets of Bufei Yishen formula (BYF) for the treatment of chronic obstructive pulmonary disease (COPD). In addition, we established a rat model of cigarette smoke- and bacterial infection-induced COPD to validate the mechanisms of BYF action that were predicted in systems pharmacology study. The systems pharmacology model derived 216 active compounds from BYF and 195 potential targets related to various diseases. The compound-target network showed that each herbal drug in the BYF formula acted on similar targets, suggesting potential synergistic effects among these herbal drugs. The ClueGo assay, a Cytoscape plugin, revealed that most targets were related to activation of MAP kinase and matrix metalloproteinases. By using target-diseases network analysis, we found that BYF had great potential to treatment of multiple diseases, such as respiratory tract diseases, immune system, and cardiovascular diseases. Furthermore, we found that BYF had the ability to prevent COPD and its comorbidities, such as ventricular hypertrophy, in vivo. Moreover, BYF inhibited the inflammatory cytokine, and hypertrophic factors expression, protease-antiprotease imbalance and the collagen deposition, which may be the underlying mechanisms of action of BYF. PMID:26469778

  19. Pharmacologic Therapies in Anticoagulation.

    PubMed

    Ferreira, Joana Lima; Wipf, Joyce E

    2016-07-01

    Anticoagulants are beneficial for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation. The development of target-specific oral anticoagulants is changing the landscape of anticoagulation therapy and created growing interest on this subject. Understanding the pharmacology of different anticoagulants is the first step to adequately treat patients with best available therapy while avoiding serious bleeding complications. This article reviews the pharmacology of the main anticoagulant classes (vitamin K antagonists, direct oral anticoagulants, and heparins) and their clinical indications based on evidence-based data currently available in the literature. PMID:27235611

  20. The Pharmacology of Immunosuppression

    PubMed Central

    2009-01-01

    Objective To provide students with a comprehensive, integrated presentation on the pharmacology of immuosuppression. Design Course content on the pharmacology of immunosuppression relating to organ transplantation and treatment of autoimmune disorders was presented in integrated sequence modules that included content from pharmacology, medicinal chemistry, and therapeutics. Weekly recitation sessions and active-learning exercises were incorporated to allow students to apply the information they learned to integrated patient cases and stimulate involvement and critical thinking. Fundamental material related to the components and functions of the immune system was presented to students early in curriculum with courses such as biochemistry, pathophysiology, and immunology/microbiology. Assessment Comprehensive examinations, in-class quizzes, written case submissions, case discussions, review exercises, and group exercises were used to assess student learning. Conclusion Students at South University received a comprehensive and detailed understanding of all aspects relating to immunosuppressive therapy. This was accomplished by integrating instruction on immunosuppressive therapy from various disciplines. PMID:20221337

  1. Ongoing Transmission of Onchocerca volvulus after 25 Years of Annual Ivermectin Mass Treatments in the Vina du Nord River Valley, in North Cameroon

    PubMed Central

    Eisenbarth, Albert; Achukwi, Mbunkah Daniel; Renz, Alfons

    2016-01-01

    Background Recent reports of transmission interruption of Onchocerca volvulus, the causing agent of river blindness, in former endemic foci in the Americas, and more recently in West and East Africa, raise the question whether elimination of this debilitating disease is underway after long-term treatment of the population at risk with ivermectin. The situation in Central Africa has not yet been clearly assessed. Methods and findings Entomologic data from two former endemic river basins in North Cameroon were generated over a period of 43 and 48 months to follow-up transmission levels in areas under prolonged ivermectin control. Moreover, epidemiologic parameters of animal-borne Onchocerca spp. transmitted by the same local black fly vectors of the Simulium damnosum complex were recorded and their impact on O. volvulus transmission success evaluated. With mitochondrial DNA markers we unambiguously confirmed the presence of infective O. volvulus larvae in vectors from the Sudan savannah region (mean Annual Transmission Potential 2009–2012: 98, range 47–221), but not from the Adamawa highland region. Transmission rates of O. ochengi, a parasite of Zebu cattle, were high in both foci. Conclusions/significance The high cattle livestock density in conjunction with the high transmission rates of the bovine filaria O. ochengi prevents the transmission of O. volvulus on the Adamawa plateau, whereas transmission in a former hyperendemic focus was markedly reduced, but not completely interrupted after 25 years of ivermectin control. This study may be helpful to gauge the impact of the presence of animal-filariae for O. volvulus transmission in terms of the growing human and livestock populations in sub-Saharan countries. PMID:26926855

  2. [Ongoing Health Education in Brazil:education or ongoing management?].

    PubMed

    Lemos, Cristiane Lopes Simão

    2016-03-01

    The scope of this study was to analyze the concept and principles of Ongoing Health Education (OHE) - the Brazilian acronym is PNEPS. The methodology was based on the analysis of documents from the Ministry of Health and related scientific articles. It was revealed that the concept of OHE transcends its pedagogical significance and is undergoing a service restructuring process in the face of the new demands of the model. Precisely at the time in which jobs are increasingly unstable and precarious, the Ministry of Health engages in discourse regarding innovative management, focusing on the issue of OHE. The idea is not one of ongoing education, but of ongoing management. Rather than being an instrument for radical transformation, OHE becomes an attractive ideology due to its appearance as a pedagogical novelty. PMID:26960103

  3. Systems pharmacology-based approach for dissecting the active ingredients and potential targets of the Chinese herbal Bufei Jianpi formula for the treatment of COPD

    PubMed Central

    Zhao, Peng; Li, Jiansheng; Li, Ya; Tian, Yange; Wang, Yonghua; Zheng, Chunli

    2015-01-01

    Background The Chinese herbal Bufei Jianpi formula (BJF) provides an effective treatment option for chronic obstructive pulmonary disease (COPD). However, the systems-level mechanism underlying the clinical effects of BJF on COPD remains unknown. Methods In this study, a systems pharmacology model based on absorption filtering, network targeting, and systems analyses was applied specifically to clarify the active compounds and therapeutic mechanisms of BJF. Then, a rat model of cigarette smoke- and bacterial infection-induced COPD was used to investigate the therapeutic mechanisms of BJF on COPD and its comorbidity. Results The pharmacological system successfully identified 145 bioactive ingredients from BJF and revealed 175 potential targets. There was a significant target overlap between the herbal constituents of BJF. These results suggested that each herb of BJF connected with similar multitargets, indicating potential synergistic effects among them. The integrated target–disease network showed that BJF probably was efficient for the treatment of not only respiratory tract diseases but also other diseases, such as nervous system and cardiovascular diseases. The possible mechanisms of action of BJF were related to activation of inflammatory response, immune responses, and matrix metalloproteinases, among others. Furthermore, we demonstrated that BJF treatment could effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production in vivo. Conclusion This study using the systems pharmacology method, in combination with in vivo experiments, helped us successfully dissect the molecular mechanism of BJF for the treatment of COPD and predict the potential targets of the multicomponent BJF, which provides a new approach to illustrate the synergetic mechanism of the complex prescription and discover more effective drugs against COPD

  4. Analysis of 50 patients with atypical odontalgia. A preliminary report on pharmacological procedures for diagnosis and treatment.

    PubMed

    Vickers, E R; Cousins, M J; Walker, S; Chisholm, K

    1998-01-01

    Atypical odontalgia is a distressing and unusual chronic orofacial pain condition. It is often difficult to diagnose because it is associated with a lack of clinical and radiographic abnormalities. The condition is poorly understood on a pathophysiological basis, and patients often undergo repetitive and unnecessary dental procedures in attempts to alleviate pain. In this study, 50 patients diagnosed with odontalgia were evaluated by pharmacological procedures, including topical anesthetic application and phentolamine infusion. Results of these pharmacological procedures suggest that atypical odontalgia is a neuropathic pain of the oral cavity that may have a component of sympathetically maintained pain. Therapeutic trials of topical capsaicin were carried out to assess its efficacy for pain reduction. Topical capsaicin was effective in most patients. PMID:9474610

  5. Pharmacological strategies for detoxification

    PubMed Central

    Diaper, Alison M; Law, Fergus D; Melichar, Jan K

    2014-01-01

    Detoxification refers to the safe discontinuation from a substance of dependence and is distinct from relapse prevention. Detoxification usually takes between a few days and a few weeks to complete, depending on the substance being misused, the severity of dependence and the support available to the user. Psychosocial therapies alongside pharmacological treatments are essential to improve outcome. The dependencies considered in this overview are detoxification from opioids (with methadone, buprenorphine, α2-adrenoceptor agonists and adjunct medications), alcohol (with benzodiazepines, anti-glutamatergics and γ-aminobutyric acid (GABA)-ergic drugs), stimulants and cannabis (with no clear recommended pharmacological treatments), benzodiazepines (with dose tapering) and nicotine (with nicotine replacement therapy, antidepressants and partial agonists). Evidence is limited by a lack of controlled trials robust enough for review bodies, and more research is required into optimal treatment doses and regimes, alone and in combination. PMID:24118014

  6. Pharmacological management of sepsis

    SciTech Connect

    Fletcher, J.R.

    1985-01-01

    Systemic sepsis continues to be the most-difficult management problem in caring for the combat casualty. The complications of sepsis pervade all areas of injury to soldiers in the field, whether it is mechanical (missiles), thermal (burns), chemical, biological, or radiation injury. With the advent of tactical nuclear weapons, the problem of sepsis will be much higher in future wars than has previously been experienced through the world. The purpose of this chapter is a) to review the data suggesting pharmacological agents that may benefit the septic patient, and b) to emphasize the adjunctive therapies that should be explored in clinical trials. The pharmacological management of sepsis remains controversial. Most of the drugs utilized clinically treat the symptoms of the disease and are not necessarily directed at fundamental mechanisms that are known to be present in sepsis. A broad data base is emerging, indicating that NSAID should be used in human clinical trials. Prostaglandins are sensitive indicators of cellular injury and may be mediators for a number of vasoactive chemicals. Opiate antagonists and calcium channel blockers require more in-depth data; however, recent studies generate excitement for their potential use in the critically ill patient. Pharmacological effects of antibiotics, in concert with other drugs, suggest an entirely new approach to pharmacological treatment in sepsis. There is no doubt that new treatment modalities or adjunctive therapies must be utilized to alter the poor prognosis of severe sepsis that we have observed in the past 4 decades.

  7. Development and pharmacological evaluation of in vitro nanocarriers composed of lamellar silicates containing copaiba oil-resin for treatment of endometriosis.

    PubMed

    de Almeida Borges, Vinícius Raphael; da Silva, Julianna Henriques; Barbosa, Samantha Soares; Nasciutti, Luiz Eurico; Cabral, Lúcio Mendes; de Sousa, Valeria Pereira

    2016-07-01

    In this work, newly developed nanocomposites based upon lamellar silicates are evaluated to determine their potential in controlling endometriosis. The preparation of the new nanocarriers is detailed, properties characterized and in vitro pharmacological evaluation performed. The nanocomposites in this study were obtained from the reaction of copaiba oil-resin (COPA) with the polymer polyvinylpyrrolidone (PVP K-30). COPA was selected due to its antiinflammatory and anticancer activities along with the organophilic derivatives of sodium montmorillonite, Viscogel B8, S7 and S4. The results indicated that it was feasible to obtain a good yield of a COPA nanocomposite using a simple process. Intercalation was confirmed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). In vitro release experiments demonstrated that COPA was released from the nanocomposite in a delayed fashion. Whereas, in vitro pharmacological studies showed a reduction in viability and proliferation of endometriotic cell cultures upon COPA nanocomposite treatment, suggesting that the system developed here can be a promising alternative therapy for the oral treatment of endometriosis. PMID:27127058

  8. A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

    PubMed Central

    Vincenzi, Fabrizio; Padovan, Melissa; Targa, Martina; Corciulo, Carmen; Giacuzzo, Sarah; Merighi, Stefania; Gessi, Stefania; Govoni, Marcello; Borea, Pier Andrea; Varani, Katia

    2013-01-01

    A2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A2AAR stimulation in a rat model of arthritis. We investigated A2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A2AARs in lymphocytes from RA patients. The effectiveness of A2AAR stimulation in a rat model of arthritis supported the role of A2AAR agonists as potential pharmacological treatment for RA. PMID:23326596

  9. Cholangiocarcinoma: Biology, Clinical Management, and Pharmacological Perspectives

    PubMed Central

    Macias, Rocio I. R.

    2014-01-01

    Cholangiocarcinoma (CCA), or tumor of the biliary tree, is a rare and heterogeneous group of malignancies associated with a very poor prognosis. Depending on their localization along the biliary tree, CCAs are classified as intrahepatic, perihilar, and distal, and these subtypes are now considered different entities that differ in tumor biology, the staging system, management, and prognosis. When diagnosed, an evaluation by a multidisciplinary team is essential; the team must decide on the best therapeutic option. Surgical resection of tumors with negative margins is the best option for all subtypes of CCA, although this is only achieved in less than 50% of cases. Five-year survival rates have increased in the recent past owing to improvements in imaging techniques, which permits resectability to be predicted more accurately, and in surgery. Chemotherapy and radiotherapy are relatively ineffective in treating nonoperable tumors and the resistance of CCA to these therapies is a major problem. Although the combination of gemcitabine plus platinum derivatives is the pharmacological treatment most widely used, to date there is no standard chemotherapy, and new combinations with targeted drugs are currently being tested in ongoing clinical trials. This review summarizes the biology, clinical management, and pharmacological perspectives of these complex tumors. PMID:27335842

  10. Molecular and Physiological Factors of Neuroprotection in Hypoxia-tolerant Models: Pharmacological Clues for the Treatment of Stroke

    PubMed Central

    Nathaniel, Thomas I; Soyinka, Julius O; Adedeji, Adekunle; Imeh-Nathaniel, Adebobola

    2015-01-01

    The naked mole-rat possesses several unique physiological and molecular features that underlie their remarkably and exceptional resistance to tissue hypoxia. Elevated pattern of Epo, an erythropoietin (Epo) factor; c-fos; vascular endothelial growth factor (VEGF); and hypoxia-inducible factors (HIF-1α) contribute to the adaptive strategy to cope with hypoxic stress. Moreover, the naked mole-rat has a lower metabolic rate than any other eutherian mammal of comparable size that has been studied. The ability to actively reduce metabolic rate represents a strategy widely used in the face of decreased tissue oxygen availability. Understanding the different molecular and physiological factors that induce metabolic suppression could guide the development of pharmacological agents for the clinical management of stroke patient. PMID:25780340

  11. Epigenetic pathway targets for the treatment of disease: accelerating progress in the development of pharmacological tools: IUPHAR Review 11

    PubMed Central

    Tough, David F; Lewis, Huw D; Rioja, Inmaculada; Lindon, Matthew J; Prinjha, Rab K

    2014-01-01

    The properties of a cell are determined both genetically by the DNA sequence of its genes and epigenetically through processes that regulate the pattern, timing and magnitude of expression of its genes. While the genetic basis of disease has been a topic of intense study for decades, recent years have seen a dramatic increase in the understanding of epigenetic regulatory mechanisms and a growing appreciation that epigenetic misregulation makes a significant contribution to human disease. Several large protein families have been identified that act in different ways to control the expression of genes through epigenetic mechanisms. Many of these protein families are finally proving tractable for the development of small molecules that modulate their function and represent new target classes for drug discovery. Here, we provide an overview of some of the key epigenetic regulatory proteins and discuss progress towards the development of pharmacological tools for use in research and therapy. PMID:25060293

  12. Ex vivo culture of Drosophila pupal testis and single male germ-line cysts: dissection, imaging, and pharmacological treatment.

    PubMed

    Gärtner, Stefanie M K; Rathke, Christina; Renkawitz-Pohl, Renate; Awe, Stephan

    2014-01-01

    During spermatogenesis in mammals and in Drosophila melanogaster, male germ cells develop in a series of essential developmental processes. This includes differentiation from a stem cell population, mitotic amplification, and meiosis. In addition, post-meiotic germ cells undergo a dramatic morphological reshaping process as well as a global epigenetic reconfiguration of the germ line chromatin-the histone-to-protamine switch. Studying the role of a protein in post-meiotic spermatogenesis using mutagenesis or other genetic tools is often impeded by essential embryonic, pre-meiotic, or meiotic functions of the protein under investigation. The post-meiotic phenotype of a mutant of such a protein could be obscured through an earlier developmental block, or the interpretation of the phenotype could be complicated. The model organism Drosophila melanogaster offers a bypass to this problem: intact testes and even cysts of germ cells dissected from early pupae are able to develop ex vivo in culture medium. Making use of such cultures allows microscopic imaging of living germ cells in testes and of germ-line cysts. Importantly, the cultivated testes and germ cells also become accessible to pharmacological inhibitors, thereby permitting manipulation of enzymatic functions during spermatogenesis, including post-meiotic stages. The protocol presented describes how to dissect and cultivate pupal testes and germ-line cysts. Information on the development of pupal testes and culture conditions are provided alongside microscope imaging data of live testes and germ-line cysts in culture. We also describe a pharmacological assay to study post-meiotic spermatogenesis, exemplified by an assay targeting the histone-to-protamine switch using the histone acetyltransferase inhibitor anacardic acid. In principle, this cultivation method could be adapted to address many other research questions in pre- and post-meiotic spermatogenesis. PMID:25286189

  13. Similitude in modern pharmacology.

    PubMed

    Teixeira, M Z

    1999-07-01

    The principle of the similitude, the basis of homeopathy, has correspondences in the clinical studies of secondary effects of many modern pharmaceutical agents through the observation of the rebound effects of these drugs. Through clinical pharmacology, I proposed a model on which to base the scientificism of the homeopathic model. We have studied the effects of the drugs in the human body using pharmacological compendia and recent scientific works, confirming the mechanism of the homeopathic medicines' action through the verification of the primary action of the drugs and the consequent secondary reaction of the organism in hundreds of pharmaceutical agents. Treatment exploiting the "rebound" effect (curative vital reaction) may also be observed. This work suggests a research methodology to scientifically base the therapeutic principle of similitude. PMID:10449051

  14. Prediction of Efficacy of Vabicaserin, a 5-HT2C Agonist, for the Treatment of Schizophrenia Using a Quantitative Systems Pharmacology Model

    PubMed Central

    Liu, J; Ogden, A; Comery, T A; Spiros, A; Roberts, P; Geerts, H

    2014-01-01

    A quantitative systems pharmacology model that combines in vitro/preclinical neurophysiology data, human imaging data, and patient disease information was used to blindly predict steady-state clinical efficacy of vabicaserin, a 5-HT2C full agonist, in monotherapy and, subsequently, to assess adjunctive therapy in schizophrenia. The model predicted a concentration-dependent improvement of positive and negative syndrome scales (PANSS) in schizophrenia monotherapy with vabicaserin. At the exposures of 100 and 200 mg b.i.d., the predicted improvements on PANSS in virtual patient trials were 5.12 (2.20, 8.56) and 6.37 (2.27, 10.40) (mean (95% confidence interval)), respectively, which are comparable to the observed phase IIa results. At the current clinical exposure limit of vabicaserin, the model predicted an ~9-point PANSS improvement in monotherapy, and <4-point PANSS improvement adjunctive with various antipsychotics, suggesting limited clinical benefit of vabicaserin in schizophrenia treatment. In conclusion, the updated quantitative systems pharmacology model of PANSS informed the clinical development decision of vabicaserin in schizophrenia. PMID:24759548

  15. Vocal local versus pharmacological treatments for pain management in tubal ligation procedures in rural Kenya: a non-inferiority trial

    PubMed Central

    2014-01-01

    Background Vocal local (VL) is a non-pharmacological pain management technique for gynecological procedures. In Africa, it is usually used in combination with pharmacological analgesics. However, analgesics are associated with side-effects, and can be costly and subject to frequent stock-outs, particularly in remote rural settings. We compared the effectiveness of VL + local anesthesia + analgesics (the standard approach), versus VL + local anesthesia without analgesics, on pain and satisfaction levels for women undergoing tubal ligations in rural Kenya. Methods We conducted a site-randomised non-inferiority trial of 884 women receiving TLs from 40 Marie Stopes mobile outreach sites in Kisii and Machakos Districts. Twenty sites provided VL + local anesthesia + analgesics (control), while 20 offered VL + local anesthesia without additional analgesics (intervention). Pain was measured using a validated 11-point Numeric Rating Scale; satisfaction was measured using 11-point scales. Results A total of 461 women underwent tubal ligations with VL + local anesthesia, while 423 received tubal ligations with VL + local anesthesia + analgesics. The majority were aged ≥30 years (78%), and had >3 children (99%). In a multivariate analysis, pain during the procedure was not significantly different between the two groups. The pain score after the procedure was significantly lower in the intervention group versus the control group (by 0.40 points; p = 0.041). Satisfaction scores were equally high in both groups; 96% would recommend the procedure to a friend. Conclusion VL + local anesthesia is as effective as VL + local anesthesia + analgesics for pain management during tubal ligation in rural Kenya. Avoiding analgesics is associated with numerous benefits including cost savings and fewer issues related to the maintenance, procurement and monitoring of restricted opioid drugs, particularly in remote low-resource settings

  16. Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder.

    PubMed

    Mørk, A; Pehrson, A; Brennum, L T; Nielsen, S Møller; Zhong, H; Lassen, A B; Miller, S; Westrich, L; Boyle, N J; Sánchez, C; Fischer, C W; Liebenberg, N; Wegener, G; Bundgaard, C; Hogg, S; Bang-Andersen, B; Stensbøl, T Bryan

    2012-03-01

    1-[2-(2,4-Dimethylphenyl-sulfanyl)-phenyl]-piperazine (Lu AA21004) is a human (h) serotonin (5-HT)(3A) receptor antagonist (K(i) = 3.7 nM), h5-HT(7) receptor antagonist (K(i) = 19 nM), h5-HT(1B) receptor partial agonist (K(i) = 33 nM), h5-HT(1A) receptor agonist (K(i) = 15 nM), and a human 5-HT transporter (SERT) inhibitor (K(i) = 1.6 nM) (J Med Chem 54:3206-3221, 2011). Here, we confirm that Lu AA21004 is a partial h5-HT(1B) receptor agonist [EC(50) = 460 nM, intrinsic activity = 22%] using a whole-cell cAMP-based assay and demonstrate that Lu AA21004 is a rat (r) 5-HT(7) receptor antagonist (K(i) = 200 nM and IC(50) = 2080 nM). In vivo, Lu AA21004 occupies the r5-HT(1B) receptor and rSERT (ED(50) = 3.2 and 0.4 mg/kg, respectively) after subcutaneous administration and is a 5-HT(3) receptor antagonist in the Bezold-Jarisch reflex assay (ED(50) = 0.11 mg/kg s.c.). In rat microdialysis experiments, Lu AA21004 (2.5-10.0 mg/kg s.c.) increased extracellular 5-HT, dopamine, and noradrenaline in the medial prefrontal cortex and ventral hippocampus. Lu AA21004 (5 mg/kg per day for 3 days; minipump subcutaneously), corresponding to 41% rSERT occupancy, significantly increased extracellular 5-HT in the ventral hippocampus. Furthermore, the 5-HT(3) receptor antagonist, ondansetron, potentiated the increase in extracellular levels of 5-HT induced by citalopram. Lu AA21004 has antidepressant- and anxiolytic-like effects in the rat forced swim (Flinders Sensitive Line) and social interaction and conditioned fear tests (minimal effective doses: 7.8, 2.0, and 3.9 mg/kg). In conclusion, Lu AA21004 mediates its pharmacological effects via two pharmacological modalities: SERT inhibition and 5-HT receptor modulation. In vivo, this results in enhanced release of several neurotransmitters and antidepressant- and anxiolytic-like profiles at doses for which targets in addition to the SERT are occupied. The multimodal activity profile of Lu AA21004 is distinct from that of current

  17. Recent treatment advances and novel therapeutic approaches in epilepsy

    PubMed Central

    Serrano, Enrique

    2015-01-01

    The purpose of this article is to review recent advances in the treatment of epilepsy. It includes five antiepileptic drugs that have been recently added to the pharmacologic armamentarium and surgical techniques that have been developed in the last few years. Finally, we review ongoing research that may have a potential role in future treatments of epilepsy. PMID:26097734

  18. A Systems-Pharmacology Analysis of Herbal Medicines Used in Health Improvement Treatment: Predicting Potential New Drugs and Targets

    PubMed Central

    Liu, Jianling; Pei, Mengjie; Zheng, Chunli; Li, Yan; Wang, Yonghua; Lu, Aiping; Yang, Ling

    2013-01-01

    For thousands of years, tonic herbs have been successfully used all around the world to improve health, energy, and vitality. However, their underlying mechanisms of action in molecular/systems levels are still a mystery. In this work, two sets of tonic herbs, so called Qi-enriching herbs (QEH) and Blood-tonifying herbs (BTH) in TCM, were selected to elucidate why they can restore proper balance and harmony inside body, organ and energy system. Firstly, a pattern recognition model based on artificial neural network and discriminant analysis for assessing the molecular difference between QEH and BTH was developed. It is indicated that QEH compounds have high lipophilicity while BTH compounds possess high chemical reactivity. Secondly, a systematic investigation integrating ADME (absorption, distribution, metabolism, and excretion) prediction, target fishing and network analysis was performed and validated on these herbs to obtain the compound-target associations for reconstructing the biologically-meaningful networks. The results suggest QEH enhance physical strength, immune system and normal well-being, acting as adjuvant therapy for chronic disorders while BTH stimulate hematopoiesis function in body. As an emerging approach, the systems pharmacology model might facilitate to understand the mechanisms of action of the tonic herbs, which brings about new development for complementary and alternative medicine. PMID:24369484

  19. Levobetaxolol hydrochloride: a review of its pharmacology and use in the treatment of chronic open-angle glaucoma and ocular hypertension.

    PubMed

    Quaranta, Luciano; Turano, Raffaele; Pizzolante, Teodoro

    2007-06-01

    Levobetaxolol is a cardioselective beta-blocker that has been demonstrated to reduce intraocular pressure in patients affected with primary open-angle glaucoma and ocular hypertension. Levobetaxolol may be an effective neuroprotectant because of its great capacity to block sodium and calcium influx, which might confer a neuroprotective activity. Experimental and clinical studies have demonstrated the effects of levobetaxolol on ocular hemodynamics and visual field, and the pharmacologic differences between beta-blockers currently used for the treatment of elevated IOP have become of more than academic interest since a number of studies have shown improvements to various extents. Unlike the initially manufactured 0.5% ophthalmic solution, levobetaxolol is suspended in a different delivery vehicle in levobetaxolol ophthalmic suspension, to increase the ocular tolerance and allow a similarity of effect with a 2-fold reduced concentration (0.25%). PMID:19668496

  20. Levobetaxolol hydrochloride: a review of its pharmacology and use in the treatment of chronic open-angle glaucoma and ocular hypertension

    PubMed Central

    Quaranta, Luciano; Turano, Raffaele; Pizzolante, Teodoro

    2007-01-01

    Levobetaxolol is a cardioselective β-blocker that has been demonstrated to reduce intraocular pressure in patients affected with primary open-angle glaucoma and ocular hypertension. Levobetaxolol may be an effective neuroprotectant because of its great capacity to block sodium and calcium influx, which might confer a neuroprotective activity. Experimental and clinical studies have demonstrated the effects of levobetaxolol on ocular hemodynamics and visual field, and the pharmacologic differences between β-blockers currently used for the treatment of elevated IOP have become of more than academic interest since a number of studies have shown improvements to various extents. Unlike the initially manufactured 0.5% ophthalmic solution, levobetaxolol is suspended in a different delivery vehicle in levobetaxolol ophthalmic suspension, to increase the ocular tolerance and allow a similarity of effect with a 2-fold reduced concentration (0.25%). PMID:19668496

  1. Trauma-Focused CBT for Youth who Experience Ongoing Traumas

    PubMed Central

    Cohen, Judith A.; Mannarino, Anthony P.; Murray, Laura A.

    2011-01-01

    Many youth experience ongoing trauma exposure, such as domestic or community violence. Clinicians often ask whether evidence-based treatments containing exposure components to reduce learned fear responses to historical trauma are appropriate for these youth. Essentially the question is, if youth are desensitized to their trauma experiences, will this in some way impair their responding to current or ongoing trauma? The paper addresses practical strategies for implementing one evidence-based treatment, Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for youth with ongoing traumas. Collaboration with local therapists and families participating in TF-CBT community and international programs elucidated effective strategies for applying TF-CBT with these youth. These strategies included: 1) enhancing safety early in treatment; 2) effectively engaging parents who experience personal ongoing trauma; and 3) during the trauma narrative and processing component focusing on a) increasing parental awareness and acceptance of the extent of the youths’ ongoing trauma experiences; b) addressing youths’ maladaptive cognitions about ongoing traumas; and c) helping youth differentiate between real danger and generalized trauma reminders. Case examples illustrate how to use these strategies in diverse clinical situations. Through these strategies TF-CBT clinicians can effectively improve outcomes for youth experiencing ongoing traumas. PMID:21855140

  2. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders.

    PubMed

    Masliah, E; Díez-Tejedor, E

    2012-04-01

    Neurotrophic factors are considered as part of the therapeutic strategy for neurological disorders like dementia, stroke and traumatic brain injury. Cerebrolysin is a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair. In dementia models, Cerebrolysin decreases β-amyloid deposition and microtubule-associated protein tau phosphorylation by regulating glycogen synthase kinase-3β and cyclin-dependent kinase 5 activity, increases synaptic density and restores neuronal cytoarchitecture. These effects protect integrity of the neuronal circuits and thus result in improved cognitive and behavioral performance. Furthermore, Cerebrolysin enhances neurogenesis in the dentate gyrus, the basis for neuronal replacement therapy in neurodegenerative diseases. Experimental studies in stroke animal models have shown that Cerebrolysin stabilizes the structural integrity of cells by inhibition of calpain and reduces the number of apoptotic cells after ischemic lesion. Cerebrolysin induces restorative processes, decreases infarct volume and edema formation and promotes functional recovery. Stroke-induced neurogenesis in the subventricular zone was also promoted by Cerebrolysin, thus supporting the brain's self-repair after stroke. Both, traumatic brain and spinal cord injury conditions stimulate the expression of natural neurotrophic factors to promote repair and regeneration processes -axonal regeneration, neuronal plasticity and neurogenesis- that is considered to be crucial for the future recovery. Neuroprotective effects of Cerebrolysin on experimentally induced traumatic spinal cord injury have shown that Cerebrolysin prevents apoptosis of lesioned motoneurons and promotes functional recovery. This section summarizes the most relevant data on the pharmacology of Cerebrolysin obtained from in vitro assays (biochemical and cell cultures) and in vivo animal models of acute and chronic neurological disorders. PMID

  3. The successful pharmacological treatment of adolescents and young adults with borderline personality disorder: a preliminary open trial of flupenthixol.

    PubMed

    Kutcher, S; Papatheodorou, G; Reiter, S; Gardner, D

    1995-03-01

    Borderline personality disorder is a significantly disabling disturbance often arising in adolescents or young adults. In the absence of demonstrated effective treatments in this population, this open prospective study evaluated the effect of low dose (3 mg per day) flupenthixol in 13 rigorously diagnosed adolescents with borderline personality disorder. Therapeutic outcome over eight weeks of treatment assessed across measures of impulsivity, depression/dysphoria, general psychopathology and global functioning showed significant improvement in all spheres. These findings suggest that low dose flupenthixol may have a role to play in the short-term treatment of this population. PMID:7703220

  4. Antihypertensive Pharmacology

    PubMed Central

    Gerber, John G.; Freed, Curt R.; Nies, Alan S.

    1980-01-01

    Although drug treatment of hypertension is associated with improved survival and decreased vascular complications, drug compliance is a major problem in the control of hypertension. All antihypertensive medications are associated with side effects; thus, it is a physician's responsibility to explain to each patient the side effects of the drugs he prescribes to treat hypertension, and to instill in the patient a sense of necessity for the treatment of hypertension. The choice of antihypertensive drug should be made based on each patient's lifestyle, overall health and ability to tolerate the drug. Ideally, the antihypertensive regimen should be simple, effective, convenient to take and have very few side effects. PMID:6992462

  5. A dose-ranging study of behavioral and pharmacological treatment in social settings for children with ADHD.

    PubMed

    Pelham, William E; Burrows-MacLean, Lisa; Gnagy, Elizabeth M; Fabiano, Gregory A; Coles, Erika K; Wymbs, Brian T; Chacko, Anil; Walker, Kathryn S; Wymbs, Frances; Garefino, Allison; Hoffman, Martin T; Waxmonsky, James G; Waschbusch, Daniel A

    2014-08-01

    Placebo and three doses of methylphenidate (MPH) were crossed with 3 levels of behavioral modification (no behavioral modification, NBM; low-intensity behavioral modification, LBM; and high-intensity behavior modification, HBM) in the context of a summer treatment program (STP). Participants were 48 children with ADHD, aged 5-12. Behavior was examined in a variety of social settings (sports activities, art class, lunch) that are typical of elementary school, neighborhood, and after-school settings. Children received each behavioral condition for 3 weeks, order counterbalanced across groups. Children concurrently received in random order placebo, 0.15 mg/kg/dose, 0.3 mg/kg/dose, or 0.6 mg/kg/dose MPH, 3 times daily with dose manipulated on a daily basis in random order for each child. Both behavioral and medication treatments produced highly significant and positive effects on children's behavior. The treatment modalities also interacted significantly. Whereas there was a linear dose-response curve for medication in NBM, the dose-response curves flattened considerably in LBM and HBM. Behavior modification produced effects as large as moderate doses, and on some measures, high doses of medication. These results replicate and extend to social-recreational settings previously reported results in a classroom setting from the same sample (Fabiano et al., School Psychology Review, 36, 195-216, 2007). Results illustrate the importance of taking dosage/intensity into account when evaluating combined treatments; there were no benefits of combined treatments when the dosage of either treatment was high but combination of the low-dose treatments produced substantial incremental improvement over unimodal treatment. PMID:24429997

  6. Clinical pharmacology and malaria.

    PubMed

    Breckenridge, A M; Winstanley, P A

    1997-10-01

    The role of clinical pharmacology in improving the prevention and treatment of malaria is reviewed. A series of general and specific issues is discussed, concentrating on risk-benefit and cost-effectiveness. The techniques of clinical pharmacokinetics play an important role in the optimal use of drugs and this is illustrated by studies on quinine and proguanil. In discussing amodiaquine toxicity, the role of the pharmacologist and the chemist in designing out drug toxicity lends hope for producing a new generation of antimalarial drugs. PMID:9625927

  7. Neuroimmune pharmacological approaches

    PubMed Central

    Holzer, Peter; Hassan, Ahmed; Jain, Piyush; Reichmann, Florian; Farzi, Aitak

    2016-01-01

    Intestinal inflammation is a major health problem which impairs the quality of life, impacts mental health and is exacerbated by stress and psychiatric disturbances which, in turn, can affect disease prognosis and response to treatment. Accumulating evidence indicates that the immune system is an important interface between intestinal inflammation and the enteric, sensory, central and autonomic nervous systems. In addition, the neuroimmune interactions originating from the gastrointestinal tract are orchestrated by the gut microbiota. This article reviews some major insights into this complex homeostatic network that have been achieved during the past two years and attempts to put these advances into perspective with novel opportunities of pharmacological intervention. PMID:26426677

  8. Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs – provision of due diligence in the treatment process

    PubMed Central

    Zajdel, Justyna

    2013-01-01

    Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on “off-label use”. The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug. PMID:24592133

  9. Developmental Pharmacology

    ERIC Educational Resources Information Center

    van den Anker, Johannes N.

    2010-01-01

    Understanding the pharmacokinetics and pharmacodynamics of drugs used in psychopharmacology across the pediatric age spectrum from infants to adolescents represents a major challenge for clinicians. In pediatrics, treatment protocols use either standard dose reductions for these drugs for children below a certain age or use less conventional…

  10. Pharmacological and haematological results of rat skin burn injury treatment with Cu(II)2(3,5-diisopropylsalicylate)4.

    PubMed

    Malakyan, Margarita H; Bajinyan, Sergey A; Abrahamyan, Armenuhi K; Petrosyan, Zhasmena H; Harutyunyan, Nektar K; Badiryan, Vardush A; Sorenson, John R J

    2004-01-01

    This research was performed to determine whether or not treatment of burn-injured rats with Cu(II)2(3,5-diisopropylsalicylate)4(Cu(II)2(3,5-DIPS)4) facilitated recovery from burn-injury. Four groups of adult male rats received a standard skin burn 1 h before an initial subcutaneous treatment which was continued daily for three days with either 0, 5, 10 or 20micromol Cu(II)2(3,5-DIPS)4/kg body mass. A fifth group was given no treatment. A sixth group served as a non-burn-injured non-treated normal control group. At 3 h and on days 1, 2, 3, 7 and 14 post-burn-injury blood samples were obtained from rats in all groups for the determination of leukocyte, platelet and erythrocyte counts, clotting times, hemoglobin and hematocrit values. Total protein and middle mass peptides in plasma, as well as plasma lipid and erythrocyte membrane peroxidation products were determined on days 7 and 14. Burn wound healing and body mass were determined daily from day 0 to 6 with a notation of crust rejection by day 14. Treatment with Cu(II)2(3,5-DIPS)4 produced effects consistent with a facilitation of Cu-dependent immune-mediated physiological inflammatory responses to burn injury. It is concluded that treatment of burn injury with Cu(II)2(3,5-DIPS)4 supports Cu-dependent physiological responses involved in overcoming burn injury, which may have been further optimized by continued treatment beyond day 2, the last day of treatment. PMID:15901413

  11. Systematic Review of Randomized Clinical Trials on Safety and Efficacy of Pharmacological and Nonpharmacological Treatments for Retinitis Pigmentosa

    PubMed Central

    Sacchetti, Marta; Mantelli, Flavio; Merlo, Daniela; Lambiase, Alessandro

    2015-01-01

    Aims. Several treatments have been proposed to slow down progression of Retinitis pigmentosa (RP), a hereditary retinal degenerative condition leading to severe visual impairment. The aim of this study is to systematically review data from randomized clinical trials (RCTs) evaluating safety and efficacy of medical interventions for the treatment of RP. Methods. Randomized clinical trials on medical treatments for syndromic and nonsyndromic RP published up to December 2014 were included in the review. Visual acuity, visual field, electroretinogram, and adverse events were used as outcome measures. Results. The 19 RCTs included in this systematic review included trials on hyperbaric oxygen delivery, topical brimonidine tartrate, vitamins, docosahexaenoic acid, gangliosides, lutein, oral nilvadipine, ciliary neurotrophic factor, and valproic acid. All treatments proved safe but did not show significant benefit on visual function. Long term supplementation with vitamin A showed a significantly slower decline rate in electroretinogram amplitude. Conclusions. Although all medical treatments for RP appear safe, evidence emerging from RCTs is limited since they do not present comparable results suitable for quantitative statistical analysis. The limited number of RCTs, the poor clinical results, and the heterogeneity among studies negatively influence the strength of recommendations for the long term management of RP patients. PMID:26339504

  12. Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.

    PubMed

    Busby, Robert W; Kessler, Marco M; Bartolini, Wilmin P; Bryant, Alexander P; Hannig, Gerhard; Higgins, Carolyn S; Solinga, Robert M; Tobin, Jenny V; Wakefield, James D; Kurtz, Caroline B; Currie, Mark G

    2013-01-01

    Linaclotide, a potent guanylate cyclase C agonist, is a therapeutic peptide approved in the United States for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. We present for the first time the metabolism, degradation, and disposition of linaclotide in animals and humans. We examined the metabolic stability of linaclotide in conditions that mimic the gastrointestinal tract and characterized the metabolite MM-419447 (CCEYCCNPACTGC), which contributes to the pharmacologic effects of linaclotide. Systemic exposure to these active peptides is low in rats and humans, and the low systemic and portal vein concentrations of linaclotide and MM-419447 observed in the rat confirmed both peptides are minimally absorbed after oral administration. Linaclotide is stable in the acidic environment of the stomach and is converted to MM-419447 in the small intestine. The disulfide bonds of both peptides are reduced in the small intestine, where they are subsequently proteolyzed and degraded. After oral administration of linaclotide, <1% of the dose was excreted as active peptide in rat feces and a mean of 3-5% in human feces; in both cases MM-419447 was the predominant peptide recovered. MM-419447 exhibits high-affinity binding in vitro to T84 cells, resulting in a significant, concentration-dependent accumulation of intracellular cyclic guanosine-3',5'-monophosphate (cGMP). In rat models of gastrointestinal function, orally dosed MM-419447 significantly increased fluid secretion into small intestinal loops, increased intraluminal cGMP, and caused a dose-dependent acceleration in gastrointestinal transit. These results demonstrate the importance of the active metabolite in contributing to linaclotide's pharmacology. PMID:23090647

  13. Recent Advances in the Development of Novel Pharmacological Agents for the Treatment of Cognitive Impairments in Schizophrenia

    PubMed Central

    Buchanan, Robert W.; Freedman, Robert; Javitt, Daniel C.; Abi-Dargham, Anissa; Lieberman, Jeffrey A.

    2007-01-01

    Wayne Fenton was a major driving force behind the establishment of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and Treatment Units for Research on Neurocognition and Schizophrenia (TURNS) project mechanisms. These projects were designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia. The MATRICS project identified 3 drug mechanisms of particular interest: cholinergic, dopaminergic, and glutamatergic. The TURNS project is designed to select potential cognitive-enhancing agents and evaluate their potential efficacy in the context of proof of concept or clinical efficacy trials. This article reviews the rationale for these 3 approaches and provides an update on the development of therapeutic agents, which act through one of these 3 mechanisms. PMID:17641146

  14. Differential pharmacology and clinical utility of preservative-free tafluprost in the treatment of ocular hypertension and glaucoma

    PubMed Central

    Ermiş, Sıtkı Samet

    2012-01-01

    Glaucoma is a chronic disease requiring lifelong treatment. Discomfort due to medications may affect patients’ quality of life and may cause poor compliance, which leads to poor intraocular pressure control. To minimize the side effects of long-term treatment, preparations with lower benzalkonium chloride concentrations, preservative-free preparations and alternative preservatives have been developed and reported to have a lower rate of side effects. Tafluprost, launched on the ophthalmic market in 2008, is a new 16-phenoxy analogue of prostaglandin F2α, clinically used as an ocular hypotensive agent for the treatment of glaucoma and ocular hypertension. The safety and intraocular pressure-lowering efficacy of tafluprost has been demonstrated in various preclinical and clinical studies. PMID:22654492

  15. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis

    PubMed Central

    Cilfone, NA; Pienaar, E; Thurber, GM; Kirschner, DE; Linderman, JJ

    2015-01-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  16. Ongoing hydrothermal activities within Enceladus.

    PubMed

    Hsu, Hsiang-Wen; Postberg, Frank; Sekine, Yasuhito; Shibuya, Takazo; Kempf, Sascha; Horányi, Mihály; Juhász, Antal; Altobelli, Nicolas; Suzuki, Katsuhiko; Masaki, Yuka; Kuwatani, Tatsu; Tachibana, Shogo; Sirono, Sin-iti; Moragas-Klostermeyer, Georg; Srama, Ralf

    2015-03-12

    Detection of sodium-salt-rich ice grains emitted from the plume of the Saturnian moon Enceladus suggests that the grains formed as frozen droplets from a liquid water reservoir that is, or has been, in contact with rock. Gravitational field measurements suggest a regional south polar subsurface ocean of about 10 kilometres thickness located beneath an ice crust 30 to 40 kilometres thick. These findings imply rock-water interactions in regions surrounding the core of Enceladus. The resulting chemical 'footprints' are expected to be preserved in the liquid and subsequently transported upwards to the near-surface plume sources, where they eventually would be ejected and could be measured by a spacecraft. Here we report an analysis of silicon-rich, nanometre-sized dust particles (so-called stream particles) that stand out from the water-ice-dominated objects characteristic of Saturn. We interpret these grains as nanometre-sized SiO2 (silica) particles, initially embedded in icy grains emitted from Enceladus' subsurface waters and released by sputter erosion in Saturn's E ring. The composition and the limited size range (2 to 8 nanometres in radius) of stream particles indicate ongoing high-temperature (>90 °C) hydrothermal reactions associated with global-scale geothermal activity that quickly transports hydrothermal products from the ocean floor at a depth of at least 40 kilometres up to the plume of Enceladus. PMID:25762281

  17. Physical, Mental, and Social Catastrophic Cognitions as Prognostic Factors in Cognitive-Behavioral and Pharmacological Treatments for Panic Disorder

    ERIC Educational Resources Information Center

    Hicks, Thomas V.; Leitenberg, Harold; Barlow, David H.; Gorman, Jack M.; Shear, Katherine M.; Woods, Scott W.

    2005-01-01

    The authors explored the prognostic value of 3 different types of catastrophic cognitions in the treatment of panic disorder with and without mild-to-moderate agoraphobia using a sample of 143 participants who received either cognitive-behavioral therapy (CBT) or imipramine in a randomized controlled trial. Stronger fears of social catastrophes…

  18. Comparative Safety of Pharmacologic Treatments for Persistent Depressive Disorder: A Systematic Review and Network Meta-Analysis

    PubMed Central

    Meister, Ramona; von Wolff, Alessa; Mohr, Hannes; Härter, Martin; Nestoriuc, Yvonne; Hölzel, Lars; Kriston, Levente

    2016-01-01

    We aimed to compare the safety of antidepressants for the treatment of persistent depressive disorder (PDD) with each other and with placebo. We conducted a systematic electronic search and included randomized controlled trials that investigated antidepressants for the treatment of PDD in adults. Outcomes were the incidence of experiencing any adverse event, specific adverse events and related treatment discontinuations. We analyzed the data using traditional and network meta-analyses. Thirty-four studies that comprised 4,769 patients and examined 20 individual agents in nine substance classes were included. Almost all analyzed substance classes were associated with higher discontinuation rates than placebo including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), antipsychotics, and the serotonin antagonist and reuptake inhibitor (SARI) trazodone. The odds of experiencing any adverse event were significantly higher for TCAs and serotonin noradrenaline reuptake inhibitors (SNRIs) compared to placebo. Pairwise comparisons among the substance classes revealed that more patients receiving TCAs or SNRIs experienced any adverse event and that more patients receiving TCAs or the SARI trazodone discontinued treatment. The complementary treatment with acetyl-l-carnitine showed lower rates of experiencing any adverse event and related discontinuations than all other comparators. TCAs were primarily associated with (anti-)cholinergic and sedating adverse events. SSRIs primarily showed gastrointestinal adverse events. Patients treated with the antipsychotic amisulpride were more likely to manifest weight gain and endocrine adverse events. The comparative evidence for further agents was insufficient or lacking. The identified safety differences may be used to inform the selection among the antidepressants. PMID:27187783

  19. Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents

    PubMed Central

    Ramasamy, S; Liu, CQ; Tran, H; Gubala, A; Gauci, P; McAllister, J; Vo, T

    2010-01-01

    The use of biological agents has generally been confined to military-led conflicts. However, there has been an increase in non-state-based terrorism, including the use of asymmetric warfare, such as biological agents in the past few decades. Thus, it is becoming increasingly important to consider strategies for preventing and preparing for attacks by insurgents, such as the development of pre- and post-exposure medical countermeasures. There are a wide range of prophylactics and treatments being investigated to combat the effects of biological agents. These include antibiotics (for both conventional and unconventional use), antibodies, anti-virals, immunomodulators, nucleic acids (analogues, antisense, ribozymes and DNAzymes), bacteriophage therapy and micro-encapsulation. While vaccines are commercially available for the prevention of anthrax, cholera, plague, Q fever and smallpox, there are no licensed vaccines available for use in the case of botulinum toxins, viral encephalitis, melioidosis or ricin. Antibiotics are still recommended as the mainstay treatment following exposure to anthrax, plague, Q fever and melioidosis. Anti-toxin therapy and anti-virals may be used in the case of botulinum toxins or smallpox respectively. However, supportive care is the only, or mainstay, post-exposure treatment for cholera, viral encephalitis and ricin – a recommendation that has not changed in decades. Indeed, with the difficulty that antibiotic resistance poses, the development and further evaluation of techniques and atypical pharmaceuticals are fundamental to the development of prophylaxis and post-exposure treatment options. The aim of this review is to present an update on prophylaxis and post-exposure treatment recommendations and research initiatives for biological agents in the open literature from 2007 to 2009. PMID:20860656

  20. An International Survey-based Algorithm for the Pharmacologic Treatment of Chorea in Huntington’s Disease

    PubMed Central

    Burgunder, Jean-Marc; Guttman, Mark; Perlman, Susan; Goodman, Nathan; van Kammen, Daniel P.; Goodman, LaVonne

    2011-01-01

    It is generally believed that treatments are available to manage chorea in Huntington’s disease (HD). However, lack of evidence prevents the establishment of treatment guidelines. The HD chorea research literature fails to address the indications for drug treatment, drug selection, drug dosing and side effect profiles, management of inadequate response to a single drug, and preferred drug when behavioral symptoms comorbid to chorea are present. Because there is lack of an evidence base to inform clinical decision-making, we surveyed an international group of experts to address these points. Survey results showed that patient stigma, physical injury, gait instability, work interference, and disturbed sleep were indications for a drug treatment trial. However, the experts did not agree on first choice of chorea drug, with the majority of experts in Europe favoring an antipsychotic drug (APD), and a near equal split in first choice between an APD and tetrabenazine (TBZ) among experts from North America and Australia. All experts chose an APD when comorbid psychotic or aggressive behaviors were present, or when active depression prevented the use of TBZ. However, there was agreement from all geographic regions that both APDs and TBZ were acceptable as monotherapy in other situations. Perceived efficacy and side effect profiles were similar for APDs and TBZ, except for depression as a significant side effect of TBZ. Experts used a combination of an APD and TBZ when treatment required both drugs for control of chorea and a concurrent comorbid symptom, or when severe chorea was inadequately controlled by either drug alone. The benzodiazepines (BZDs) were judged ineffective as monotherapy but useful as adjunctive therapy, particularly when chorea was exacerbated by anxiety. There was broad disagreement about the use of amantadine for chorea. Experts who had used amantadine described its benefit as small and transient. In addition to survey results, this report reviews

  1. Clinical pharmacology and vascular risk.

    PubMed

    Silvestrelli, G; Corea, F; Micheli, S; Lanari, A

    2010-01-01

    Pharmacological treatment and several drugs of abuse have been associated with ischemic heart disease (IHD) and cerebrovascular diseases (CVD). However, there is a paucity of data on the independent risk of vascular disease (VD) associated with pharmacological treatment and no controlled trials demonstrating a reduction in risk with abstinence. Information about IHD and CVD-related drug abuse is mainly limited to epidemiological studies focused on urban populations. The potential link between some pharmacological treatments (estrogen, some oncologic drugs and some atypical antipsychotics) and cerebrovascular adverse events was analyzed, but disagreement about an association persists. Drugs of abuse, including cocaine, amphetamines and heroin, have been associated with an increased vascular risk. These drugs can cause abrupt changes in blood pressure, vasculitic-type changes, lead to embolization caused by infective endocarditis, and hemostatic and hematologic abnormalities that can result in increased blood viscosity and platelet aggregation. Long-term treatment strategies based on medication, psychological support, and outreach programs play an important role in treatment of drug dependency. In these last years public interest in risk factors for VD has been constantly increasing and the successful identification and management of pharmacological treatment and drug abuse can be challenging. One of the major public health issues for the future will be to focus more on new vascular risk factor recognition and management. The objective of this chapter is to review the relevance of IHD and CVD associated with various pharmacological treatments and drug abuse with focusing on ischemic disease. This chapter reports the clinical evidence of this association and analyzes the experimental role of new drugs as a growing risk factor of VD with the hypothetical new association. In conclusion, in this chapter great attention is paid to evaluating the scientific and real

  2. Ongoing incestuous abuse during adulthood.

    PubMed

    Middleton, Warwick

    2013-01-01

    Individual cases of adult incestuous abuse have surfaced repeatedly in the lay and professional literature of the past 1.5 centuries without it occasioning systematic investigation, such as the reporting of a case series of individuals subjected to such extreme abuse. Yet substantial numbers of patients with dissociative identity disorder at the time of presentation report incestuous abuse continuing into the adult years, and for many the abuse is ongoing. Data relating to a series of 10 such incestuously abused women are presented. These patients were sexually abused from a very early age (typically from before age 3), with the manipulation of their sexual response a key component in conditioning an enduring sexualized attachment. Shame and fear were also used to ensure compliance and silence. The women, when able to speak of it, describe the induction by their paternal abuser of orgasm at an early age, typically around the age of 6. The women have high indices of self-harm and suicidality and are prone to placing themselves in dangerous reenactment scenarios. The average duration of incestuous abuse for this group of women was 31 years, and the average estimate of total episodes of sexual abuse was 3,320. Most women do not feel that they own their body and experience being "fused" to their father. Their mother was reported as an active participant in the sexual abuse or as having done nothing to protect their daughter despite seeing obvious evidence of incest. The fathers, despite a propensity to use or threaten violence, were generally outwardly productively employed, financially comfortable, and stably married and half had close church involvement. However, suicide and murder occurred within the 1st- or 2nd-degree relatives of these women at a high frequency. All 10 had been sexually abused by various groupings of individuals connected to their fathers. PMID:23627476

  3. Combining non-pharmacological treatments with pharmacotherapies for neurological disorders: a unique interface of the brain, drug-device, and intellectual property.

    PubMed

    Bulaj, Grzegorz

    2014-01-01

    Mobile medical applications (mHealth), music, and video games are being developed and tested for their ability to improve pharmacotherapy outcomes and medication adherence. Pleiotropic mechanism of music and gamification engages an intrinsic motivation and the brain reward system, supporting therapies in patients with neurological disorders, including neuropathic pain, depression, anxiety, or neurodegenerative disorders. Based on accumulating results from clinical trials, an innovative combination treatment of epilepsy seizures, comorbidities, and the medication non-adherence can be designed, consisting of antiepileptic drugs and disease self-management software delivering clinically beneficial music. Since creative elements and art expressed in games, music, and software are copyrighted, therefore clinical and regulatory challenges in developing copyrighted, drug-device therapies may be offset by a value proposition of the exclusivity due to the patent-independent protection, which can last for over 70 years. Taken together, development of copyrighted non-pharmacological treatments (e-therapies), and their combinations with pharmacotherapies, offer incentives to chronically ill patients and outcome-driven health care industries. PMID:25071711

  4. Combining Non-Pharmacological Treatments with Pharmacotherapies for Neurological Disorders: A Unique Interface of the Brain, Drug–Device, and Intellectual Property

    PubMed Central

    Bulaj, Grzegorz

    2014-01-01

    Mobile medical applications (mHealth), music, and video games are being developed and tested for their ability to improve pharmacotherapy outcomes and medication adherence. Pleiotropic mechanism of music and gamification engages an intrinsic motivation and the brain reward system, supporting therapies in patients with neurological disorders, including neuropathic pain, depression, anxiety, or neurodegenerative disorders. Based on accumulating results from clinical trials, an innovative combination treatment of epilepsy seizures, comorbidities, and the medication non-adherence can be designed, consisting of antiepileptic drugs and disease self-management software delivering clinically beneficial music. Since creative elements and art expressed in games, music, and software are copyrighted, therefore clinical and regulatory challenges in developing copyrighted, drug–device therapies may be offset by a value proposition of the exclusivity due to the patent–independent protection, which can last for over 70 years. Taken together, development of copyrighted non-pharmacological treatments (e-therapies), and their combinations with pharmacotherapies, offer incentives to chronically ill patients and outcome-driven health care industries. PMID:25071711

  5. Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools.

    PubMed

    Silva, Juliana; Monge-Fuentes, Victoria; Gomes, Flávia; Lopes, Kamila; dos Anjos, Lilian; Campos, Gabriel; Arenas, Claudia; Biolchi, Andréia; Gonçalves, Jacqueline; Galante, Priscilla; Campos, Leandro; Mortari, Márcia

    2015-08-01

    Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer's Disease, Parkinson's Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. PMID:26295258

  6. Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools

    PubMed Central

    Silva, Juliana; Monge-Fuentes, Victoria; Gomes, Flávia; Lopes, Kamila; dos Anjos, Lilian; Campos, Gabriel; Arenas, Claudia; Biolchi, Andréia; Gonçalves, Jacqueline; Galante, Priscilla; Campos, Leandro; Mortari, Márcia

    2015-01-01

    Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer’s Disease, Parkinson’s Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. PMID:26295258

  7. Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model.

    PubMed

    Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

    2015-12-01

    Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by the systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. PMID:26232641

  8. Pharmacologic Treatment of Depression in Older Patients with COPD: Impact on the Course of the Disease and Health Outcomes

    PubMed Central

    Yohannes, AM; Alexopoulos, GS

    2015-01-01

    Over 40% older chronic obstructive pulmonary disease (COPD) patients suffer from clinically significant depressive symptoms that may interfere in their daily activities. Untreated depression may increase physical disability, social isolation, hopelessness and healthcare utilization. This review examined the impact of depression on the course of COPD, and the efficacy of antidepressant drugs therapy and their implication for clinical practice. The efficacy of antidepressants from the published trials in patients with COPD has been inconclusive. Specifically, there has been no clear evidence that antidepressants can induce remission of depression or ameliorate dyspnoea or physiological indices of COPD. Both the selective reuptake inhibitors (SSRI) and tricycle antidepressant (TCA) studies conducted in depressed COPD patients have been significantly limited by methodological weaknesses including low sample size, sample heterogeneity, and variability in scales used to diagnose and to monitor the treatment of depression. For this reason, it remains unclear whether which SSRIs or TCAs should be favoured in the treatment of depressed COPD patients and what is an appropriate dosage and duration range. Simply offering antidepressant drugs to older depressed COPD patients is unlikely to improve their conditions. Promising treatment strategies such as cognitive behavioural therapy and collaborative care approach should be considered with or without antidepressants drug therapy for depressed COPD patients. Further studies are needed with large randomised controlled trials to examine the efficacy of antidepressants in patients with COPD with long-term follow-up. PMID:24902934

  9. Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease.

    PubMed

    Huang, Xiao-Tian; Qian, Zhong-Ming; He, Xuan; Gong, Qi; Wu, Ka-Chun; Jiang, Li-Rong; Lu, Li-Na; Zhu, Zhou-Jing; Zhang, Hai-Yan; Yung, Wing-Ho; Ke, Ya

    2014-05-01

    Huperzine A (HupA), a natural inhibitor of acetylcholinesterase derived from a plant, is a licensed anti-Alzheimer's disease (AD) drug in China and a nutraceutical in the United States. In addition to acting as an acetylcholinesterase inhibitor, HupA possesses neuroprotective properties. However, the relevant mechanism is unknown. Here, we showed that the neuroprotective effect of HupA was derived from a novel action on brain iron regulation. HupA treatment reduced insoluble and soluble beta amyloid levels, ameliorated amyloid plaques formation, and hyperphosphorylated tau in the cortex and hippocampus of APPswe/PS1dE9 transgenic AD mice. Also, HupA decreased beta amyloid oligomers and amyloid precursor protein levels, and increased A Disintegrin And Metalloprotease Domain 10 (ADAM10) expression in these treated AD mice. However, these beneficial effects of HupA were largely abolished by feeding the animals with a high iron diet. In parallel, we found that HupA decreased iron content in the brain and demonstrated that HupA also has a role to reduce the expression of transferrin-receptor 1 as well as the transferrin-bound iron uptake in cultured neurons. The findings implied that reducing iron in the brain is a novel mechanism of HupA in the treatment of Alzheimer's disease. PMID:24332448

  10. Evaluation of a pharmacist intervention on patients initiating pharmacological treatment for depression: a randomized controlled superiority trial.

    PubMed

    Rubio-Valera, Maria; March Pujol, Marian; Fernández, Ana; Peñarrubia-María, M Teresa; Travé, Pere; López Del Hoyo, Yolanda; Serrano-Blanco, Antoni

    2013-09-01

    Major depression is associated with high burden, disability and costs. Non-adherence limits the effectiveness of antidepressants. Community pharmacists (CP) are in a privileged position to help patients cope with antidepressant treatment. The aim of the study was to evaluate the impact of a CP intervention on primary care patients who had initiated antidepressant treatment. Newly diagnosed primary care patients were randomised to usual care (UC) (92) or pharmacist intervention (87). Patients were followed up at 6 months and evaluated three times (Baseline, and at 3 and 6 months). Outcome measurements included clinical severity of depression (PHQ-9), health-related quality of life (HRQOL) (Euroqol-5D) and satisfaction with pharmacy care. Adherence was continuously registered from the computerised pharmacy records. Non-adherence was defined as refilling less than 80% of doses or having a medication-free gap of more than 1 month. Patients in the intervention group were more likely to remain adherent at 3 and 6 months follow-up but the difference was not statistically significant. Patients in the intervention group showed greater statistically significant improvement in HRQOL compared with UC patients both in the main analysis and PP analyses. No statistically significant differences were observed in clinical symptoms or satisfaction with the pharmacy service. The results of our study indicate that a brief intervention in community pharmacies does not improve depressed patients' adherence or clinical symptoms. This intervention helped patients to improve their HRQOL, which is an overall measure of patient status. PMID:23219937

  11. An International Survey-based Algorithm for the Pharmacologic Treatment of Obsessive-Compulsive Behaviors in Huntington’s Disease

    PubMed Central

    Anderson, Karen; Craufurd, David; Edmondson, Mary C.; Goodman, Nathan; Groves, Mark; van Duijn, Erik; van Kammen, Daniel P.; Goodman, LaVonne

    2011-01-01

    It is generally believed that treatments are available to manage obsessive-compulsive behaviors (OCB's) in Huntington’s disease (HD). However, lack of an evidence base prevents guideline development. The research literature fails to address the indications for behavioral interventions, drug selection, drug dosing, management of inadequate response to a single drug, and preferred drugs when additional behavioral symptoms comorbid to OCBs are present. In an effort to inform clinical decision-making, we surveyed an international group of experts to address these points. Survey results showed that experts utilized behavioral therapy only for patients with mild cognitive impairment. There was expert agreement that a selective serotonin reuptake inhibitor (SSRI) was the first choice drug, although clomipramine (CMI) was cited as a monotherapy choice by the smaller number of experts familiar with its use. Perceived efficacy for control of OCBs was similar for both SSRIs and CMI. Though less favored choices overall, antipsychotics (APDs) and antiepileptic mood stabilizers (AEDs) were most often used as augmentation strategies. In addition to survey results, this report reviews available studies, and lastly presents an algorithm for the treatment of OCBs in HD based on practice-based preferences obtained from this survey. PMID:21947193

  12. Ongoing challenges in the management of malaria

    PubMed Central

    Kokwaro, Gilbert

    2009-01-01

    This article gives an overview of some of the ongoing challenges that are faced in the prevention, diagnosis and treatment of malaria. Malaria causes approximately 881,000 deaths every year, with nine out of ten deaths occurring in sub-Saharan Africa. In addition to the human burden of malaria, the economic burden is vast. It is thought to cost African countries more than US$12 billion every year in direct losses. However, great progress in malaria control has been made in some highly endemic countries. Vector control is assuming a new importance with the significant reductions in malaria burden achieved using combined malaria control interventions in countries such as Zanzibar, Zambia and Rwanda. The proportion of patients treated for malaria who have a confirmed diagnosis is low in Africa compared with other regions of the world, with the result that anti-malarials could be used to treat patients without malaria, especially in areas where progress has been made in reducing the malaria burden and malaria epidemiology is changing. Inappropriate administration of anti-malarials could contribute to the spread of resistance and incurs unnecessary costs. Parasite resistance to almost all commonly used anti-malarials has been observed in the most lethal parasite species, Plasmodium falciparum. This has presented a major barrier to successful disease management in malaria-endemic areas. ACT (artemisinin-based combination therapy) has made a significant contribution to malaria control and to reducing disease transmission through reducing gametocyte carriage. Administering ACT to infants and small children can be difficult and time consuming. Specially formulating anti-malarials for this vulnerable population is vital to ease administration and help ensure that an accurate dose is received. Education of healthworkers and communities about malaria prevention, diagnosis and treatment is a vital component of effective case management, especially as diagnostic policies change

  13. Pharmacological evaluation of nasal delivery of selegiline hydrochloride-loaded thiolated chitosan nanoparticles for the treatment of depression.

    PubMed

    Singh, Devendra; Rashid, Muzamil; Hallan, Supandeep Singh; Mehra, Neelesh Kumar; Prakash, Atish; Mishra, Neeraj

    2016-05-01

    The aim of the present study was to investigate the propensity of thiolated chitosan nanoparticles (TCNs) to enhance the nasal delivery of selegiline hydrochloride. TCNs were synthesized by the ionic gelation method. The particle size distribution (PDI), entrapment efficiency (EE), and zeta potential of modified chitosan (CS) nanoparticles were found to be 215 ± 34.71 nm, 70 ± 2.71%, and + 17.06 mV, respectively. The forced swim and the tail suspension tests were used to evaluate the anti-depressant activity, in which elevated immobility time was found to reduce on treatment. TCNs seem to be promising candidates for nose-to-brain delivery in the evaluation of antidepressant activity. PMID:26042481

  14. Efficacy and safety of pharmacological interventions in second- or later-line treatment of patients with advanced soft tissue sarcoma: a systematic review

    PubMed Central

    2013-01-01

    Background Current guidelines recommend anthracycline-based chemotherapy primarily with doxorubicin either as monotherapy or in combination with ifosfamide as the first-line treatment for most advanced STS subtypes. Therapeutic options after failure of doxorubicin and/or ifosfamide are limited. This study aimed to comprehensively review available data on the activity and safety of interventions in second- or later-line treatment of advanced STS. Methods Electronic literature databases (Embase®, MEDLINE®, MEDLINE® In-Process, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) were searched from 1980 to 01 March 2012 to identify randomised controlled trials (RCTs) and non-randomised studies (both prospective and retrospective) evaluating pharmacological interventions in patients with advanced STS pre-treated with anthracycline- and/or ifosfamide-based therapy. Results The review identified six RCTs (one phase III and five phase II trials) and 94 non-randomised studies. Based on the primary trial endpoints, RCTs demonstrated favourable efficacy for pazopanib over placebo (PFS: 4.6 months vs. 1.6 months), gemcitabine plus dacarbazine over dacarbazine monotherapy (3-month PFS rate: 54.2% vs. 35.2%), and trabectedin 3-weekly schedule over weekly schedule (TTP: 3.7 months vs. 2.3 months. The non-randomised studies demonstrated heterogeneity in efficacy and safety results. Conclusions Across the RCTs, pazopanib over placebo, gemcitabine-dacarbazine over dacarbazine, and trabectedin 3-weekly over weekly regimen clearly demonstrated a PFS advantage in the second- and later-line treatment of advanced STS. With only one phase III trial in this setting, there is a clear need for additional comparative trials to better understand the risk: benefit ratios of available agents and combinations. PMID:23937858

  15. Molecular Mechanisms of Action and Therapeutic Uses of Pharmacological Inhibitors of HIF–Prolyl 4-Hydroxylases for Treatment of Ischemic Diseases

    PubMed Central

    Selvaraju, Vaithinathan; Parinandi, Narasimham L.; Adluri, Ram Sudheer; Goldman, Joshua W.; Hussain, Naveed; Sanchez, Juan A.

    2014-01-01

    Abstract Significance: In this review, we have discussed the efficacy and effect of small molecules that act as prolyl hydroxylase domain inhibitors (PHDIs). The use of these compounds causes upregulation of the pro-angiogenic factors and hypoxia inducible factor-1α and -2α (HIF-1α and HIF-2α) to enhance angiogenic, glycolytic, erythropoietic, and anti-apoptotic pathways in the treatment of various ischemic diseases responsible for significant morbidity and mortality in humans. Recent Advances: Sprouting of new blood vessels from the existing vasculature and surgical intervention, such as coronary bypass and stent insertion, have been shown to be effective in attenuating ischemia. However, the initial reentry of oxygen leads to the formation of reactive oxygen species that cause oxidative stress and result in ischemia/reperfusion (IR) injury. This apparent “oxygen paradox” must be resolved to combat IR injury. During hypoxia, decreased activity of PHDs initiates the accumulation and activation of HIF-1α, wherein the modulation of both PHD and HIF-1α appears as promising therapeutic targets for the pharmacological treatment of ischemic diseases. Critical Issues: Research on PHDs and HIFs has shown that these molecules can serve as therapeutic targets for ischemic diseases by modulating glycolysis, erythropoiesis, apoptosis, and angiogenesis. Efforts are underway to identify and synthesize safer small-molecule inhibitors of PHDs that can be administered in vivo as therapy against ischemic diseases. Future Directions: This review presents a comprehensive and current account of the existing small-molecule PHDIs and their use in the treatment of ischemic diseases with a focus on the molecular mechanisms of therapeutic action in animal models. Antioxid. Redox Signal. 20, 2631–2665. PMID:23992027

  16. Pharmacological management of acute bronchiolitis

    PubMed Central

    Wright, Melvin; Mullett, Charles J; Piedimonte, Giovanni

    2008-01-01

    This article reviews the current knowledge base related to the pharmacological treatments for acute bronchiolitis. Bronchiolitis is a common lower respiratory illness affecting infants worldwide. The mainstays of therapy include airway support, supplemental oxygen, and support of fluids and nutrition. Frequently tried pharmacological interventions, such as ribavirin, nebulized bronchodilators, and systemic corticosteroids, have not been proven to benefit patients with bronchiolitis. Antibiotics do not improve the clinical course of patients with bronchiolitis, and should be used only in those patients with proven concurrent bacterial infection. Exogenous surfactant and heliox therapy also cannot be recommended for routine use, but surfactant replacement holds promise and should be further studied. PMID:19209271

  17. Epilepsy Surgery: Current Status and Ongoing Challenges

    PubMed Central

    KAWAI, Kensuke

    2015-01-01

    This article reviews the current status of surgical treatment of epilepsy and introduces the ongoing challenges. Seizure outcome of resective surgery for focal seizures associated with focal lesions is satisfactory. Particularly for mesial temporal lobe epilepsy, surgical treatment should be considered from the earlier stage of the disease. Meanwhile, surgical outcome in nonlesional extratemporal lobe epilepsy is still to be improved using various approaches. Disconnective surgeries reduce surgical complications of extensive resections while achieving equivalent or better seizure outcomes. Multiple subpial transection is still being modified expecting a better outcome by transection to the vertical cortices along the sulci- and multi-directional transection from a single entry point. Hippocampal transection is expected to preserve memory function while interrupting the abnormal epileptic synchronization. Proper selection or combination of subdural and depth electrodes and a wide-band analysis of electroencephalography may improve the accurate localization of epileptogenic region. Patients for whom curative resective surgery is not indicated because of generalized or bilateral multiple nature of their epilepsies, neuromodulation therapies are options of treatment which palliate their seizures. PMID:25925752

  18. Pharmacologic application of native GnRH in the winter anovulatory mare, I: frequency of reversion to the anovulatory state following ovulation induction and cessation of treatment.

    PubMed

    Thorson, J F; Allen, C C; Amstalden, M; Williams, G L

    2014-03-01

    pharmacologic or managerial intervention, and mares are not pregnant, treatment must be continued at least until the end of March. This will improve the likelihood of a normal interovulatory interval after treatment withdrawal. PMID:24411221

  19. Unlock the Thermogenic Potential of Adipose Tissue: Pharmacological Modulation and Implications for Treatment of Diabetes and Obesity

    PubMed Central

    Peng, Xiao-Rong; Gennemark, Peter; O’Mahony, Gavin; Bartesaghi, Stefano

    2015-01-01

    Brown adipose tissue (BAT) is considered an interesting target organ for the treatment of metabolic disease due to its high metabolic capacity. Non-shivering thermogenesis, once activated, can lead to enhanced partitioning and oxidation of fuels in adipose tissues, and reduce the burden of glucose and lipids on other metabolic organs such as liver, pancreas, and skeletal muscle. Sustained long-term activation of BAT may also lead to meaningful bodyweight loss. In this review, we discuss three different drug classes [the thiazolidinedione (TZD) class of PPARγ agonists, β3-adrenergic receptor agonists, and fibroblast growth factor 21 (FGF21) analogs] that have been proposed to regulate BAT and beige recruitment or activation, or both, and which have been tested in both rodent and human. The learnings from these classes suggest that restoration of functional BAT and beige mass as well as improved activation might be required to fully realize the metabolic potential of these tissues. Whether this can be achieved without the undesired cardiovascular side effects exhibited by the TZD PPARγ agonists and β3-adrenergic receptor agonists remains to be resolved. PMID:26635723

  20. Chronic Pelvic Ischemia: Contribution to the Pathogenesis of Lower Urinary Tract Symptoms (LUTS): A New Target for Pharmacological Treatment?

    PubMed

    Andersson, Karl-Erik; Nomiya, Masanori; Yamaguchi, Osamu

    2015-01-01

    The incidence of lower urinary tract symptoms, including overactive bladder (OAB), is continuing to rise, and is associated with a negative impact on quality of life and a heavy economic burden. A major risk factor for OAB is advancing age. The etiology of OAB is multifactorial and appears to involve myogenic, neurogenic, and urotheliogenic factors. In this article, we review the strengthening preclinical evidence supporting the contribution of chronic pelvic ischemia to the pathogenesis of OAB. In animal models, chronic ischemia induced by arterial injury and a high-fat diet upregulates markers of oxidative stress and proinflammatory cytokines in the urothelium and lamina propria, and leads to increased expression of nerve growth factor. These processes result in increased afferent activity and an increased frequency of micturition, reflecting a state of bladder hyperactivity. In severe, prolonged cases, bladder overactivity may develop into underactivity. Antimuscarinic therapies are the mainstay of OAB treatment, but their usefulness is limited by modest efficacy and troublesome side-effects. Our increasing understanding of the contribution of chronic ischemia to OAB is leading toward novel therapeutic options targeting chronic pelvic ischemia and its morphological, functional, and oxidative consequences. Preclinical trials have demonstrated encouraging results with α1 -adrenoreceptor blockade, phosphodiesterase type 5 inhibition, β3 -adrenoreceptor agonism, free radical scavenging, and stem cell therapy, in preventing morphological, biochemical and functional changes induced by chronic bladder ischemia. PMID:26663644

  1. New developments in the pharmacological treatment of hypertension: dead-end or a glimmer at the horizon?

    PubMed

    Paulis, Ludovit; Rajkovicova, Romana; Simko, Fedor

    2015-06-01

    Arterial hypertension is the most prevalent controllable disease world-wide. Yet, we still need to further improve blood pressure control, deal with resistant hypertension, and we hope to reduce risk "beyond blood pressure." The number of candidate molecules aspiring for these aims is constantly declining. The new possible approaches to combat high blood pressure include neprilysin/neutral endopeptidase (NEP) inhibition, particularly when combined with an angiotensin receptor blockade (such as the ARNI, LCZ696), phosphodiesterase 5 (PDE5) inhibition (KD027/Slx-2101), natriuretic agents (PL3994), or a long-lasting vasointestinal peptide (VIP) analogue (PB1046). Other options exploit the protective arm of the renin-angiotensin-aldosterone system by stimulating the angiotensin AT2 receptor (compound 21), the Mas receptor (AVE-0991), or the angiotensin converting enzyme 2. Finally, we review the possibilities how to optimize the use of the available treatment options by using drug combinations or by tailoring therapy to each patient's angiotensin peptide profile. PMID:25893478

  2. Formulas used by Tibetan doctors at Men-Tsee-Khang in India for the treatment of neuropsychiatric disorders and their correlation with pharmacological data.

    PubMed

    Antonio, Raquel Luna; Kozasa, Elisa H; Galduróz, José Carlos F; Dawa; Dorjee, Yeshi; Kalsang, Tsultrim; Norbu, Tsering; Tenzin, Tashi; Rodrigues, Eliana

    2013-04-01

    The aim of the present study was to identify formulas used at Men-Tsee-Khang (Tibetan Medical and Astrological Institute), India, for the treatment of neuropsychiatric disorders and to compare the Tibetan usage of particular ingredients with pharmacological data from the scientific database. Using ethnographic methods, five doctors were selected and interviewed. A correlation was observed between central nervous system disorders and rLung, one of the three humors in Tibetan medicine, which imbalance is the source of mental disorders, and ten multi-ingredient formulas used to treat the imbalance of this particular humor were identified. These formulas utilize 61 ingredients; among them were 48 plant species. Each formula treats several symptoms related to rLung imbalance, so the plants may have therapeutic uses distinct from those of the formulas in which they are included. Myristica fragrans, nutmeg, is contained in 100% of the formulas, and its seeds exhibit stimulant and depressant actions affecting the central nervous system. Preclinical and clinical data from the scientific literature indicate that all of the formulas include ingredients with neuropsychiatric action and corroborate the therapeutic use of 75.6% of the plants. These findings indicate a level of congruence between the therapeutic uses of particular plant species in Tibetan and Western medicines. PMID:22674653

  3. Pharmacological Chaperones and Coenzyme Q10 Treatment Improves Mutant β-Glucocerebrosidase Activity and Mitochondrial Function in Neuronopathic Forms of Gaucher Disease.

    PubMed

    de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; Garrido-Maraver, Juan; Cordero, Mario D; Villanueva Paz, Marina; Delgado Pavón, Ana; Alcocer-Gómez, Elizabet; de Lavera, Isabel; Ybot-González, Patricia; Paula Zaderenko, Ana; Ortiz Mellet, Carmen; García Fernández, José M; Sánchez-Alcázar, José A

    2015-01-01

    Gaucher disease (GD) is caused by mutations in the GBA1 gene, which encodes lysosomal β-glucocerebrosidase. Homozygosity for the L444P mutation in GBA1 is associated with high risk of neurological manifestations which are not improved by enzyme replacement therapy. Alternatively, pharmacological chaperones (PCs) capable of restoring the correct folding and trafficking of the mutant enzyme represent promising alternative therapies.Here, we report on how the L444P mutation affects mitochondrial function in primary fibroblast derived from GD patients. Mitochondrial dysfunction was associated with reduced mitochondrial membrane potential, increased reactive oxygen species (ROS), mitophagy activation and impaired autophagic flux.Both abnormalities, mitochondrial dysfunction and deficient β-glucocerebrosidase activity, were partially restored by supplementation with coenzyme Q10 (CoQ) or a L-idonojirimycin derivative, N-[N'-(4-adamantan-1-ylcarboxamidobutyl)thiocarbamoyl]-1,6-anhydro-L-idonojirimycin (NAdBT-AIJ), and more markedly by the combination of both treatments. These data suggest that targeting both mitochondria function by CoQ and protein misfolding by PCs can be promising therapies in neurological forms of GD. PMID:26045184

  4. Pharmacological Chaperones and Coenzyme Q10 Treatment Improves Mutant β-Glucocerebrosidase Activity and Mitochondrial Function in Neuronopathic Forms of Gaucher Disease

    PubMed Central

    de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; Garrido-Maraver, Juan; Cordero, Mario D.; Villanueva Paz, Marina; Delgado Pavón, Ana; Alcocer-Gómez, Elizabet; de Lavera, Isabel; Ybot-González, Patricia; Paula Zaderenko, Ana; Ortiz Mellet, Carmen; Fernández, José M. García; Sánchez-Alcázar, José A.

    2015-01-01

    Gaucher disease (GD) is caused by mutations in the GBA1 gene, which encodes lysosomal β-glucocerebrosidase. Homozygosity for the L444P mutation in GBA1 is associated with high risk of neurological manifestations which are not improved by enzyme replacement therapy. Alternatively, pharmacological chaperones (PCs) capable of restoring the correct folding and trafficking of the mutant enzyme represent promising alternative therapies.Here, we report on how the L444P mutation affects mitochondrial function in primary fibroblast derived from GD patients. Mitochondrial dysfunction was associated with reduced mitochondrial membrane potential, increased reactive oxygen species (ROS), mitophagy activation and impaired autophagic flux.Both abnormalities, mitochondrial dysfunction and deficient β-glucocerebrosidase activity, were partially restored by supplementation with coenzyme Q10 (CoQ) or a L-idonojirimycin derivative, N-[N’-(4-adamantan-1-ylcarboxamidobutyl)thiocarbamoyl]-1,6-anhydro-L-idonojirimycin (NAdBT-AIJ), and more markedly by the combination of both treatments. These data suggest that targeting both mitochondria function by CoQ and protein misfolding by PCs can be promising therapies in neurological forms of GD. PMID:26045184

  5. The Vitamin D Receptor Agonist BXL-01-0029 as a Potential New Pharmacological Tool for the Treatment of Inflammatory Myopathies

    PubMed Central

    Antinozzi, Cristina; Vannelli, Gabriella Barbara; Romanelli, Francesco; Riccieri, Valeria; Valesini, Guido; Lenzi, Andrea; Crescioli, Clara

    2013-01-01

    Objective This study aims to investigate in vitro the effect of the VDR agonist BXL-01-0029 onto IFNγ/TNFα-induced CXCL10 secretion by human skeletal muscle cells compared to elocalcitol (VDR agonist), methylprednisolone, methotrexate, cyclosporin A, infliximab and leflunomide; to assess in vivo circulating CXCL10 level in subjects at time of diagnosis with IMs, before therapy, together with TNFα, IFNγ, IL-8, IL-6, MCP-1, MIP-1β and IL-10, vs. healthy subjects. Methods Human fetal skeletal muscle cells were used for in vitro studies; ELISA and Bio-Plex were used to measure cell supernatant and IC50 determination or serum cytokines; Western blot and Bio-Plex were for cell signaling analysis. Results BXL-01-0029 decreased with the highest potency IFNγ/TNFα-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFα in human skeletal muscle cells; CXCL10 level was the highest in sera of subjects diagnosed with IMs before therapy and the only one significantly different vs. healthy controls. Conclusions Our in vitro and in vivo data, while confirm the relevance of CXCL10 in IMs, suggested BXL-01-0029 as a novel pharmacological tool for IM treatment, hypothetically to be used in combination with the current immunosuppressants to minimize side effects. PMID:24204948

  6. Exercise and Pharmacological Treatment of Depressive Symptoms in Patients with Coronary Heart Disease: Results from the UPBEAT Study

    PubMed Central

    Blumenthal, James A.; Sherwood, Andrew; Babyak, Michael A.; Watkins, Lana L.; Smith, Patrick J.; Hoffman, Benson M.; O’Hayer, C. Virginia F.; Mabe, Stephanie; Johnson, Julie; Doraiswamy, P. Murali; Jiang, Wei

    2012-01-01

    OBJECTIVE To assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease (CHD). BACKGROUND Although there is good evidence that clinical depression is associated with poor prognosis, optimal therapeutic strategies are currently not well-defined. METHODS 101 outpatients with CHD and elevated depressive symptoms underwent assessment of depression including a psychiatric interview and the Hamilton Rating Scale for Depression (HAM-D). Participants were randomized to 4 months of aerobic exercise (3 times/week), sertraline (50-200 mg/day), or placebo. Additional assessments of cardiovascular biomarkers included measures of heart rate variability (HRV), endothelial function, baroreflex sensitivity, inflammation, and platelet function. RESULTS After 16 weeks, all groups showed improvement on HAM-D scores. Participants in both aerobic exercise (M= −7.5 [95% CI = −9.8, −5.0]) and sertraline (M= −6.1 [95% CI = −8.4, −3.9] achieved larger reductions in depressive symptoms compared to placebo (M= −4.5 [95% CI = −7.6, −1.5]; p = .034); exercise and sertraline were equally effective in reducing depressive symptoms (p = .607). Exercise and medication tended to result in greater improvements in HRV compared to placebo (p = .052); exercise tended to result in greater improvements in HRV compared to sertraline (p =.093) CONCLUSIONS Both exercise and sertraline resulted in greater reductions in depressive symptoms compared to placebo in CHD patients. Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as quality of life. PMID:22858387

  7. Pharmacological inhibition of HSP90 and ras activity as a new strategy in the treatment of HNSCC.

    PubMed

    Misso, Gabriella; Giuberti, Gaia; Lombardi, Angela; Grimaldi, Anna; Ricciardiello, Filippo; Giordano, Antonio; Tagliaferri, Pierosandro; Abbruzzese, Alberto; Caraglia, Michele

    2013-01-01

    Advanced head and neck squamous cell cancer (HNSCC) is currently treated with taxane-based chemotherapy. We have previously shown that docetaxel (DTX) induces a ras-dependent survival signal that can be antagonized by farnesyl transferase inhibitors (FTI) such as tipifarnib (TIP). Here we show that the synergistic TIP/DTX combination determines synergistic apoptotic conditions but, at the same time, it modulates the expression of the components of the multichaperone complex that is, in turn, involved in the regulation of the stability of members of the ras-mediated pathway. Therefore, we have stably transfected HNSCC KB and Hep-2 cells with a plasmid encoding for HSP90. The expression of the protein was increased in both transfected cell lines but its activation status was increased in Hep-2 clones and decreased in KB clones. On the basis of these results, we have treated both parental and HSP90-transfected cells with a HSP90 inhibitor geldanamycin (GA). We have found that the antiproliferative activity of GA is dependent upon the activation status of HSP90 and that it is strongly synergistic when added in combination with TIP but not with DTX in cells overexpressing HSP90 and even more in cells with increased HSP90 activity. These data were paralleled by the decreased expression and activity of the components belonging to the ras→mediated signal transduction pathway. The present results suggest that multichaperone complex activation could be a resistance mechanism to the anti-proliferative and apoptotic effects induced by TIP and that the combination of FTIs such as TIP with GA could be a suitable therapeutic strategy in the treatment of HSP90-overexpressing HNSCC. PMID:22566192

  8. Pharmacologic management of eating disorders.

    PubMed

    Price, W A

    1988-05-01

    Treatment of eating disorders is difficult regardless of the methods employed. Pharmacologic management in anorexia nervosa and in bulimia nervosa is especially helpful when it is part of a multimodal treatment approach that includes individual, family and behavioral therapy. Care must be taken to guard against side effects, abuse and noncompliance in a group of patients that tends to be prone to all three. PMID:3284300

  9. Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases.

    PubMed

    Salmon, Michael; Luttmann, Mark A; Foley, James J; Buckley, Peter T; Schmidt, Dulcie B; Burman, Miriam; Webb, Edward F; DeHaas, Christopher J; Kotzer, Charles J; Barrett, Victoria J; Slack, Robert J; Sarau, Henry M; Palovich, Michael R; Lainé, Dramane I; Hay, Douglas W P; Rumsey, William L

    2013-05-01

    Activation of muscarinic subtype 3 (M3) muscarinic cholinergic receptors (mAChRs) increases airway tone, whereas its blockade improves lung function and quality of life in patients with pulmonary diseases. The present study evaluated the pharmacological properties of a novel mAChR antagonist, GSK573719 (4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane; umeclidinium). The affinity (Ki) of GSK573719 for the cloned human M1-M5 mAChRs ranged from 0.05 to 0.16 nM. Dissociation of [(3)H]GSK573719 from the M3 mAChR was slower than that for the M2 mAChR [half-life (t1/2) values: 82 and 9 minutes, respectively]. In Chinese hamster ovary cells transfected with recombinant human M3 mAChRs, GSK573719 demonstrated picomolar potency (-log pA2 = 23.9 pM) in an acetylcholine (Ach)-mediated Ca(2+) mobilization assay. Concentration-response curves indicate competitive antagonism with partial reversibility after drug washout. Using isolated human bronchial strips, GSK573719 was also potent and showed competitive antagonism (-log pA2 = 316 pM) versus carbachol, and was slowly reversible in a concentration-dependent manner (1-100 nM). The time to 50% restoration of contraction at 10 nM was about 381 minutes (versus 413 minutes for tiotropium bromide). In mice, the ED50 value was 0.02 μg/mouse intranasally. In conscious guinea pigs, intratracheal administration of GSK573719 dose dependently blocked Ach-induced bronchoconstriction with long duration of action, and was comparable to tiotropium; 2.5 μg elicited 50% bronchoprotection for >24 hours. Thus, GSK573719 is a potent anticholinergic agent that demonstrates slow functional reversibility at the human M3 mAChR and long duration of action in animal models. This pharmacological profile translated into a 24-hour duration of bronchodilation in vivo, which suggested umeclidinium will be a once-daily inhaled treatment of pulmonary diseases. PMID:23435542

  10. Topical mometasone. A review of its pharmacological properties and therapeutic use in the treatment of dermatological disorders.

    PubMed

    Prakash, A; Benfield, P

    1998-01-01

    Mometasone, a synthetic 16 alpha-methyl analogue of beclomethasone, is classified as a 'potent' glucocorticoid for dermatological use. It is available as 0.1% cream, ointment and lotion formulations for the treatment of patients with inflammatory glucocorticoid-responsive dermatoses. In patients with atopic dermatitis, the effect of mometasone 0.1% applied once daily over 2 to 3 weeks were similar to those of other glucocorticoids of similar potency, such as betamethasone dipropionate 0.05% twice daily and methylprednisolone aceponate 0.1% once daily. Mometasone 0.1% was significantly superior to twice-daily application of less potent glucocorticoids such as clobetasone 0.05%, hydrocortisone 1.0%, hydrocortisone butyrate and hydrocortisone valerate 0.2%. In patients with seborrhoeic dermatitis, mometasone 0.1% was more effective than ketoconazole 2.0% and hydrocortisone 1.0% in trials lasting 4 or 6 weeks. In the management of scalp psoriasis and psoriasis vulgaris, mometasone 0.1% applied once daily for 2 to 8 weeks was generally more effective than other glucocorticoids of similar or weaker potency such as betamethasone valerate 0.1%, fluocinolone acetonide 0.025%, fluticasone propionate 0.005%, triamcinolone acetonide 0.1% and hydrocortisone 1.0% and as effective as diflucortolone valerate 0.1%. Alternate day application of mometasone 0.1% for 2 weeks was as effective as once-daily application in maintaining symptom control in a small number of patients with psoriasis vulgaris. Although mometasone demonstrates greater anti-inflammatory activity and a longer duration of action than betamethasone, it has low potential to cause adverse systemic effects such as suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, its atrophogenic potential is low and no greater than that of other glucocorticoids in its class, such as betamethasone valerate. Transient, mild to moderate, local adverse effects such as burning, stinging, folliculitis, dryness

  11. GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

    PubMed Central

    Busardò, Francesco P.; Jones, Alan W.

    2015-01-01

    The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant

  12. Distribution of selected elements in atherosclerotic plaques of apoE/LDLR-double knockout mice subjected to dietary and pharmacological treatments

    NASA Astrophysics Data System (ADS)

    Gajda, Mariusz; Kowalska, Joanna; Banaś, Agnieszka; Banaś, Krzysztof; Kwiatek, Wojciech M.; Kostogrys, Renata B.; Mateuszuk, łukasz; ChŁopicki, Stefan; Litwin, Jan A.; Appel, Karen

    2011-10-01

    Gene-targeted, apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice represent a new animal model that displays severe hyperlipidemia and atherosclerosis. The aim of the present study was to show changes in histomorphology and in distribution of selected elements in atherosclerotic plaques of apoE/LDLR -/- mice fed egg-rich proatherosclerotic diet (5% egg-yolk lyophilisate) supplemented or not with perindopril (inhibitor of angiotensin converting enzyme; 2 mg/kg b.w.). Synchrotron radiation micro-X-ray fluorescence spectrometry was combined with histological stainings to determine distribution and concentration of trace and essential elements in atherosclerotic lesions. More advanced atherosclerotic lesions expressed by total area occupied by lipids (oil red-O staining) and by macrophages (CD68 immunohistochemistry) were observed in animals fed egg-rich diet. The perindopril treatment attenuated these effects. No significant differences were observed in the number of intimal smooth muscle cells (smooth muscle actin immunohistochemistry). In animals fed egg-rich diet significantly higher concentrations of Ca and significantly lower contents of S, Cl, , Fe, Cu, Zn and Se in atheromas were seen in comparison to chow diet-fed animals. After pharmacological treatment, concentrations of S, Cl, Fe, Cu, Zn and Se showed the tendency to achieve levels like in animals fed normal diet. K level differed only in group treated with perindopril. Concentration of P did not significantly vary in all experimental groups. Perindopril showed its potency to reduce atherosclerosis, as estimated by the size of the atheroma and content of pro- and antiatherogenic elements.

  13. Deciphering the pharmacological mechanism of the Chinese formula Huanglian-Jie-Du decoction in the treatment of ischemic stroke using a systems biology-based strategy

    PubMed Central

    Zhang, Yan-qiong; Wang, Song-song; Zhu, Wei-liang; Ma, Yan; Zhang, Fang-bo; Liang, Ri-xin; Xu, Hai-yu; Yang, Hong-jun

    2015-01-01

    Aim: Huanglian-Jie-Du decoction (HLJDD) is an important multiherb remedy in TCM, which is recently demonstrated to be effective to treat ischemic stroke. Here, we aimed to investigate the pharmacological mechanisms of HLJDD in the treatment of ischemic stroke using systems biology approaches. Methods: Putative targets of HLJDD were predicted using MetaDrug. An interaction network of putative HLJDD targets and known therapeutic targets for the treatment of ischemic stroke was then constructed, and candidate HLJDD targets were identified by calculating topological features, including 'Degree', 'Node-betweenness', 'Closeness', and 'K-coreness'. The binding efficiencies of the candidate HLJDD targets with the corresponding compositive compounds were further validated by a molecular docking simulation. Results: A total of 809 putative targets were obtained for 168 compositive compounds in HLJDD. Additionally, 39 putative targets were common to all four herbs of HLJDD. Next, 49 major nodes were identified as candidate HLJDD targets due to their network topological importance. The enrichment analysis based on the Gene Ontology (GO) annotation system and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that candidate HLJDD targets were more frequently involved in G-protein-coupled receptor signaling pathways, neuroactive ligand-receptor interactions and gap junctions, which all played important roles in the progression of ischemic stroke. Finally, the molecular docking simulation showed that 170 pairs of chemical components and candidate HLJDD targets had strong binding efficiencies. Conclusion: This study has developed for the first time a comprehensive systems approach integrating drug target prediction, network analysis and molecular docking simulation to reveal the relationships between the herbs contained in HLJDD and their putative targets and ischemic stroke-related pathways. PMID:25937634

  14. Effects of pharmacologic treatment based on airflow limitation and breathlessness on daily physical activity in patients with chronic obstructive pulmonary disease

    PubMed Central

    Minakata, Yoshiaki; Morishita, Yukiko; Ichikawa, Tomohiro; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Ichinose, Masakazu

    2015-01-01

    Background Improvement in the daily physical activity (PA) is important for the management of chronic obstructive pulmonary disease (COPD). However, the effects of pharmacologic treatment on PA are not well understood. We evaluated the effects of additional medications, including bronchodilator with or without inhaled corticosteroid, based on airflow limitation and breathlessness on the PA in COPD patients and the factors that could predict or affect the improvement in PA. Methods A prospective non-randomized observational study was employed. Twenty-one COPD subjects without any other diseases that might reduce PA were recruited. The PA was measured with a triaxial accelerometer for 2 weeks, and pulmonary function tests and incremental shuttle walking tests were administered before and after 4-week treatment with an additional medication. Results Bronchodilation was obtained by additional medication. The mean values of PA evaluated by metabolic equivalents (METs) at ≥3.0 METs and the duration of PA at ≥3.0 METs and ≥3.5 METs were improved by medication. The % change in the duration of PA at ≥3.5 METs was significantly correlated with the baseline functional residual capacity (FRC), residual volume, and inspiratory capacity/total lung capacity. However, the % change in the duration of PA at any intensity was not correlated with the % changes of any values of the pulmonary function tests or incremental shuttle walking test except the PA at ≥2.5 METs with FRC. Conclusion Medication could improve the PA in patients with COPD, especially at a relatively high intensity of activity when medication was administered based on airflow limitation and breathlessness. The improvement was seen in the patients with better baseline lung volume, but was not correlated with the improvements in the pulmonary function tests or exercise capacity. PMID:26170656

  15. Pharmacological Study of Cefoxitin as an Alternative Antibiotic Therapy to Carbapenems in Treatment of Urinary Tract Infections Due to Extended-Spectrum-β-Lactamase-Producing Escherichia coli

    PubMed Central

    Guet-Revillet, H.; Emirian, A.; Groh, M.; Nebbad-Lechani, B.; Weiss, E.; Join-Lambert, O.; Bille, E.; Jullien, V.

    2014-01-01

    Cefoxitin could be an alternative to carbapenems in extended-spectrum-beta-lactamase-producing Escherichia coli (ESBL-EC) infections. However, pharmacological and clinical data regarding cefoxitin are limited. Using a recent pharmacological model and the MICs of ESBL-EC collected from pyelonephritis, we determined the probabilities to reach four pharmacological targets: free cefoxitin concentrations above the MIC during 50% and 100% of the administration interval (T>MIC = 50% and T>MIC = 100%, respectively) and free cefoxitin concentrations above 4× MIC during 50% and 100% of the administration interval (T>4MIC = 50% and T>4MIC = 100%, respectively). Cefoxitin could be used to treat ESBL-EC pyelonephritis, but administration modalities should be optimized according to MICs in order to reach pharmacological targets. PMID:24777104

  16. Ongoing Recovery Basic Information Tool (ORBIT)

    NASA Technical Reports Server (NTRS)

    Oberg, Donald

    1993-01-01

    The Federal Drug Free Work Place Program (DFWP) has now matured to the point of being able to return employees to sensitive testing designated positions (TDP) after completion of treatment of their addiction. The known tendency of addicted individuals to suffer multiple relapses prior to their final recovery has resulted in several positive urine tests (relapses) occurring among those Federal employees who have already completed treatment and who have been returned to TDP's. The very real potential for further relapses occurring after additional employees return to TDP's will be a critical factor in the ultimate success of the DFWP and in the public's impression of the program's effectiveness. In response to this concern, NASA has begun development of its Ongoing Recovery Basic Information Tool (ORBIT) instrument. The aim of the NASA ORBIT is to provide Employee Assistance Program (EAP) professionals with an advanced clinical tool which will be helpful in supporting recovery from substance abuse and which will allow more accurate determinations of when clients may be successfully returned to sensitive positions.

  17. Pharmacological approaches to migraine.

    PubMed

    Diener, H Ch

    2003-01-01

    Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise. This review summarises new treatment options both for the therapy of the acute attack as well as for migraine prophylaxis. Analgesics like aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) are effective in treating migraine attacks. Few controlled trials were performed for the use of ergotamine or dihydroergotamine. These trials indicate inferior efficacy compared to serotonin (5-HT)1B/D-agonists (further on called "triptans"). The triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan) are highly effective. They improve headache as well as nausea, photo- and phonophobia. The different triptans have minor differences in efficacy, headache recurrence and adverse effects. The knowledge of their different pharmacological profile allows a more specific treatment of the individual migraine characteristics. Migraine prophylaxis is recommended, when more than 3 attacks occur per month, if attacks do not respond to acute treatment or if side effects of acute treatment are severe. Substances with proven efficacy include the beta-blockers metoprolol and propranolol, the calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline. Recently antiepileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for the prophylaxis of migraine. The use of botulinum-toxin is under investigation. PMID:12830928

  18. Conus venom peptide pharmacology.

    PubMed

    Lewis, Richard J; Dutertre, Sébastien; Vetter, Irina; Christie, MacDonald J

    2012-04-01

    Conopeptides are a diverse group of recently evolved venom peptides used for prey capture and/or defense. Each species of cone snails produces in excess of 1000 conopeptides, with those pharmacologically characterized (≈ 0.1%) targeting a diverse range of membrane proteins typically with high potency and specificity. The majority of conopeptides inhibit voltage- or ligand-gated ion channels, providing valuable research tools for the dissection of the role played by specific ion channels in excitable cells. It is noteworthy that many of these targets are found to be expressed in pain pathways, with several conopeptides having entered the clinic as potential treatments for pain [e.g., pyroglutamate1-MrIA (Xen2174)] and one now marketed for intrathecal treatment of severe pain [ziconotide (Prialt)]. This review discusses the diversity, pharmacology, structure-activity relationships, and therapeutic potential of cone snail venom peptide families acting at voltage-gated ion channels (ω-, μ-, μO-, δ-, ι-, and κ-conotoxins), ligand-gated ion channels (α-conotoxins, σ-conotoxin, ikot-ikot, and conantokins), G-protein-coupled receptors (ρ-conopeptides, conopressins, and contulakins), and neurotransmitter transporters (χ-conopeptides), with expanded discussion on the clinical potential of sodium and calcium channel inhibitors and α-conotoxins. Expanding the discovery of new bioactives using proteomic/transcriptomic approaches combined with high-throughput platforms and better defining conopeptide structure-activity relationships using relevant membrane protein crystal structures are expected to grow the already significant impact conopeptides have had as both research probes and leads to new therapies. PMID:22407615

  19. Pharmacological aspects of (-)-deprenyl.

    PubMed

    Magyar, K; Pálfi, M; Tábi, T; Kalász, H; Szende, B; Szöko, E

    2004-08-01

    Deprenyl, the selective irreversible inhibitor of monoamine oxidase-B (MAO-B), has been synthesised as a potential antidepressant, however, due to its dopamine potentiating capacity, became a registered drug in the treatment of Parkinson's disease. Deprenyl possesses a wide range of pharmacological activities; some of them are not related to its MAO-B inhibitory potency. Beside its dopamine potentiating effect, it renders protection against a number of dopaminergic, cholinergic and noradrenergic neurotoxins with a complex mechanism of action. By inducing antioxidant enzymes and decreasing the formation of reactive oxygen species, deprenyl is able to combat an oxidative challenge implicated as a common causative factor in neurodegenerative diseases. In a dose substantially lower than required for MAO-B inhibition (10(-9)-10(-13) M), deprenyl interferes with early apoptotic signalling events induced by various kinds of insults in cell cultures of neuroectodermal origin, thus protecting cells from apoptotic death. Deprenyl requires metabolic conversion to a hitherto unidentified metabolite to exert its antiapoptotic effect, which serves to protect the integrity of the mitochondrion by inducing transcriptional and translational changes. Pharmacokinetic and metabolism studies have revealed that deprenyl undergoes intensive first pass metabolism, and its major metabolites also possess pharmacological activities. The ratio of the parent compound and its metabolites reaching the systemic circulation and the brain are highly dependent on the routes of administration. Therefore, in the treatment of neurodegenerative diseases, reconsideration of the dosing schedule, by lowering the dose of deprenyl and choosing the most appropriate route of administration, would diminish undesired adverse effects, with unaltered neuroprotective potency. PMID:15279565

  20. Pharmacologic Treatment of Pediatric Hypertension.

    PubMed

    Dhull, Rachita S; Baracco, Rossana; Jain, Amrish; Mattoo, Tej K

    2016-04-01

    Prevalence of hypertension is increasing in children and adolescents. Uncontrolled hypertension in children not only causes end organ damage but also increases the risk of adult hypertension and cardiovascular disease. Clinical trials have proven efficacy of antihypertensive medications in children. These medications are well tolerated by children with acceptable safety profile. The choice of agent is usually driven by underlying etiology of hypertension, profile of its side effects, and clinician's preference. This article will review currently available pediatric data on mechanism of action, common adverse effects, pediatric indication, recent clinical trial, and newer drugs in the common classes of antihypertensive medications. PMID:27048353

  1. Ceftazidime–avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections

    PubMed Central

    Lagacé-Wiens, Philippe; Walkty, Andrew; Karlowsky, James A

    2014-01-01

    Avibactam (NXL104, AVE1330A) is a semi-synthetic, non-β-lactam, β-lactamase inhibitor that is active against Ambler class A, class C, and some class D serine β-lactamases. In this review, we summarize the in vitro data, pharmacology, mechanisms of action and resistance, and clinical trial data relating to the use of this agent combined with ceftazidime for the treatment of Gram-negative bacterial infections. The addition of avibactam to ceftazidime improves its in vitro activity against Enterobacteriaceae and Pseudomonas aeruginosa. Avibactam does not improve the activity of ceftazidime against Acinetobacter spp., Burkholderia spp., or most anaerobic Gram-negative rods. Pharmacodynamic data indicate that ceftazidime—avibactam is bactericidal at concentrations achievable in human serum. Animal studies demonstrate that ceftazidime–avibactam is effective in ceftazidime-resistant Gram-negative septicemia, meningitis, pyelonephritis, and pneumonia. Limited clinical trials published to date have reported that ceftazidime–avibactam is as effective as therapy with a carbapenem in complicated urinary tract infection and complicated intra-abdominal infection (combined with metronidazole) including infection caused by cephalosporin-resistant Gram-negative isolates. Safety and tolerability of ceftazidime–avibactam in clinical trials has been excellent, with few serious drug-related adverse events reported. Given the abundant clinical experience with ceftazidime and the significant improvement that avibactam provides in its activity against contemporary β-lactamase-producing Gram-negative pathogens, it is likely this new combination agent will play a role in the empiric treatment of complicated urinary tract infections (monotherapy) and complicated intra-abdominal infections (in combination with metronidazole) caused or suspected to be caused by antimicrobial-resistant pathogens (eg, extended spectrum beta-lactamase-, AmpC-, or Klebsiella pneumoniae carbapenemase

  2. Science Selections. Accounts of Ongoing Scientific Research.

    ERIC Educational Resources Information Center

    Kornberg, Warren, Ed.

    This publication is intended to present science teachers with an opportunity to communicate to students the idea that science is an ongoing and never-ending process. The booklet contains supplemental materials, valuable as enrichment materials. A selection of ongoing research in the biological sciences, physics and astronomy, oceanography,…

  3. The Ongoing and Open-Ended Simulation

    ERIC Educational Resources Information Center

    Cohen, Alexander

    2016-01-01

    This case study explores a novel form of classroom simulation that differs from published examples in two important respects. First, it is ongoing. While most simulations represent a single learning episode embedded within a course, the ongoing simulation is a continuous set of interrelated events and decisions that accompany learning throughout…

  4. Trauma-Focused CBT for Youth Who Experience Ongoing Traumas

    ERIC Educational Resources Information Center

    Cohen, Judith A.; Mannarino, Anthony P.; Murray, Laura K.

    2011-01-01

    Many youth experience ongoing trauma exposure, such as domestic or community violence. Clinicians often ask whether evidence-based treatments containing exposure components to reduce learned fear responses to historical trauma are appropriate for these youth. Essentially the question is, if youth are desensitized to their trauma experiences, will…

  5. Pharmacological inhibition of FTO.

    PubMed

    McMurray, Fiona; Demetriades, Marina; Aik, WeiShen; Merkestein, Myrte; Kramer, Holger; Andrew, Daniel S; Scudamore, Cheryl L; Hough, Tertius A; Wells, Sara; Ashcroft, Frances M; McDonough, Michael A; Schofield, Christopher J; Cox, Roger D

    2015-01-01

    In 2007, a genome wide association study identified a SNP in intron one of the gene encoding human FTO that was associated with increased body mass index. Homozygous risk allele carriers are on average three kg heavier than those homozygous for the protective allele. FTO is a DNA/RNA demethylase, however, how this function affects body weight, if at all, is unknown. Here we aimed to pharmacologically inhibit FTO to examine the effect of its demethylase function in vitro and in vivo as a first step in evaluating the therapeutic potential of FTO. We showed that IOX3, a known inhibitor of the HIF prolyl hydroxylases, decreased protein expression of FTO (in C2C12 cells) and reduced maximal respiration rate in vitro. However, FTO protein levels were not significantly altered by treatment of mice with IOX3 at 60 mg/kg every two days. This treatment did not affect body weight, or RER, but did significantly reduce bone mineral density and content and alter adipose tissue distribution. Future compounds designed to selectively inhibit FTO's demethylase activity could be therapeutically useful for the treatment of obesity. PMID:25830347

  6. Pharmacological Inhibition of FTO

    PubMed Central

    McMurray, Fiona; Demetriades, Marina; Aik, WeiShen; Merkestein, Myrte; Kramer, Holger; Andrew, Daniel S.; Scudamore, Cheryl L.; Hough, Tertius A.; Wells, Sara; Ashcroft, Frances M.; McDonough, Michael A.; Schofield, Christopher J.; Cox, Roger D.

    2015-01-01

    In 2007, a genome wide association study identified a SNP in intron one of the gene encoding human FTO that was associated with increased body mass index. Homozygous risk allele carriers are on average three kg heavier than those homozygous for the protective allele. FTO is a DNA/RNA demethylase, however, how this function affects body weight, if at all, is unknown. Here we aimed to pharmacologically inhibit FTO to examine the effect of its demethylase function in vitro and in vivo as a first step in evaluating the therapeutic potential of FTO. We showed that IOX3, a known inhibitor of the HIF prolyl hydroxylases, decreased protein expression of FTO (in C2C12 cells) and reduced maximal respiration rate in vitro. However, FTO protein levels were not significantly altered by treatment of mice with IOX3 at 60 mg/kg every two days. This treatment did not affect body weight, or RER, but did significantly reduce bone mineral density and content and alter adipose tissue distribution. Future compounds designed to selectively inhibit FTO’s demethylase activity could be therapeutically useful for the treatment of obesity. PMID:25830347

  7. Principles of Safety Pharmacology

    PubMed Central

    Pugsley, M K; Authier, S; Curtis, M J

    2008-01-01

    Safety Pharmacology is a rapidly developing discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment. The aim of Safety Pharmacology is to characterize the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects using continuously evolving methodology. Unlike toxicology, Safety Pharmacology includes within its remit a regulatory requirement to predict the risk of rare lethal events. This gives Safety Pharmacology its unique character. The key issues for Safety Pharmacology are detection of an adverse effect liability, projection of the data into safety margin calculation and finally clinical safety monitoring. This article sets out to explain the drivers for Safety Pharmacology so that the wider pharmacology community is better placed to understand the discipline. It concludes with a summary of principles that may help inform future resolution of unmet needs (especially establishing model validation for accurate risk assessment). Subsequent articles in this issue of the journal address specific aspects of Safety Pharmacology to explore the issues of model choice, the burden of proof and to highlight areas of intensive activity (such as testing for drug-induced rare event liability, and the challenge of testing the safety of so-called biologics (antibodies, gene therapy and so on.). PMID:18604233

  8. Studies in neuroendocrine pharmacology

    NASA Technical Reports Server (NTRS)

    Maickel, R. P.

    1976-01-01

    The expertise and facilities available within the Medical Sciences Program section on Pharmacology were used along with informational input from various NASA sources to study areas relevant to the manned space effort. Topics discussed include effects of drugs on deprivation-induced fluid consumption, brain biogenic amines, biochemical responses to stressful stimuli, biochemical and behavioral pharmacology of amphetamines, biochemical and pharmacological studies of analogues to biologically active indole compounds, chemical pharmacology: drug metabolism and disposition, toxicology, and chemical methodology. Appendices include a bibliography, and papers submitted for publication or already published.

  9. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer.

    PubMed

    Du, Juan; Cieslak, John A; Welsh, Jessemae L; Sibenaller, Zita A; Allen, Bryan G; Wagner, Brett A; Kalen, Amanda L; Doskey, Claire M; Strother, Robert K; Button, Anna M; Mott, Sarah L; Smith, Brian; Tsai, Susan; Mezhir, James; Goswami, Prabhat C; Spitz, Douglas R; Buettner, Garry R; Cullen, Joseph J

    2015-08-15

    The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer. PMID:26081808

  10. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer

    PubMed Central

    Du, Juan; Cieslak, John A.; Welsh, Jessemae L.; Sibenaller, Zita A.; Allen, Bryan G.; Wagner, Brett A.; Kalen, Amanda L.; Doskey, Claire M.; Strother, Robert K.; Button, Anna M.; Mott, Sarah L.; Smith, Brian; Tsai, Susan; Mezhir, James; Goswami, Prabhat C.; Spitz, Douglas R.; Buettner, Garry R.; Cullen, Joseph J.

    2015-01-01

    The toxicity of pharmacological ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Since pancreatic cancer cells are sensitive to H2O2 generated by ascorbate they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacological ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in non-tumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacological ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacological ascorbate as a radiosensitizer in the treatment of pancreatic cancer. PMID:26081808

  11. Paradoxical pharmacology: turning our pharmacological models upside down.

    PubMed

    Page, Clive

    2011-04-01

    Paradoxical pharmacology is a term first suggested by Richard Bond to refer to intriguing observations that chronic use of some drug types can have the opposite biological effect(s) to those seen following acute administration of the same drug. A good example of 'paradoxical pharmacology' is the research Richard has pioneered showing that whereas acute administration of β-blockers is contraindicated in the treatment of asthma, chronic use of certain β-blockers can have therapeutic benefit. It would appear that those β-blockers that can act as inverse agonists at the β2 receptor particularly show this paradoxical effect and the findings of Richard's research not only challenge the dogma of the treatment of asthma but also challenge many of the pharmacological principles of ligand/receptor interactions established by Sir James Black and others. In this paper, I discuss Richard's efforts to evaluate the chronic effects of β-blockers in the airways and how this research caught the imagination of Sir James Black. PMID:21458081

  12. Curriculum Guidelines for Pharmacology.

    ERIC Educational Resources Information Center

    Shaw, David H.; And Others

    1990-01-01

    Pharmacology embraces the physical and chemical properties of drugs; the preparation of pharmaceutical agents; the absorption, fate, and excretion of drugs; and the effects of drugs on living systems. These guidelines represent a consensus on what would constitute a minimally acceptable pharmacology course for predoctoral dental students. (MLW)

  13. Pharmacology Information System Ready

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1973

    1973-01-01

    Discusses the development and future of Prophet,'' a specialized information handling system for pharmacology research. It is designed to facilitate the acquisition and dissemination of knowledge about mechanisms of drug action, and it is hoped that it will aid in converting pharmacology research from an empirical to a predictive science. (JR)

  14. Pharmacology for the Psychotherapist.

    ERIC Educational Resources Information Center

    Goldenberg, Myron Michael

    This book covers those areas of pharmacology that are of importance and interest to the psychotherapist. The 1st chapter introduces the various types of drugs. The 2nd chapter presents an overview of pharmacology and its principles. The 3rd chapter reviews aspects of the human body of importance to understanding the workings of psychotropic drugs.…

  15. Nurse Practitioner Pharmacology Education.

    ERIC Educational Resources Information Center

    Waigandt, Alex; Chang, Jane

    A study compared the pharmacology training of nurse practitioner programs with medical and dental programs. Seventy-three schools in 14 states (40 nurse practitioner programs, 19 schools of medicine, and 14 schools of dentistry) were surveyed by mailed questionnaire about the number of hours devoted to the study of pharmacology. The major findings…

  16. Integrating pharmacology and clinical pharmacology in universities.

    PubMed

    Buckingham, Julia C

    2012-06-01

    Continuing development of safe and effective new medicines is critically important for global health, social prosperity and the economy. The drug discovery-development pipeline depends critically on close partnerships between scientists and clinicians and on educational programmes that ensure that the pharmacological workforce, in its broadest sense, is fit for purpose. Here I consider factors that have influenced the development of basic and clinical pharmacology in UK universities over the past 40 years and discuss ways in which basic pharmacologists, clinical pharmacologists and scientists from different disciplines can work together effectively, while retaining their professional identities and fostering developments in their disciplines. Specifically, I propose the establishment of Institutes of Drug Discovery and Development, whose activities could include development and implementation of a translational pharmacology research strategy, drawing on the collective expertise of the membership and the university as whole; provision of a forum for regular seminars and symposia to promote the discipline, encourage collaboration and develop a cohesive community; provision of a research advisory service, covering, for example, data management, applications for ethics permission, clinical trials design, statistics and regulatory affairs; liaison with potential funders and leadership of major funding bids, including funding for doctoral training; provision of advice on intellectual property protection and the commercialization of research; liaison with corporate partners to facilitate collaboration, knowledge transfer and effective translation; and leadership of undergraduate and postgraduate education in basic and clinical pharmacology and related sciences for medical and science students, including continuing professional development and transferable skills. PMID:22360628

  17. Integrating pharmacology and clinical pharmacology in universities

    PubMed Central

    Buckingham, Julia C

    2012-01-01

    Continuing development of safe and effective new medicines is critically important for global health, social prosperity and the economy. The drug discovery–development pipeline depends critically on close partnerships between scientists and clinicians and on educational programmes that ensure that the pharmacological workforce, in its broadest sense, is fit for purpose. Here I consider factors that have influenced the development of basic and clinical pharmacology in UK universities over the past 40 years and discuss ways in which basic pharmacologists, clinical pharmacologists and scientists from different disciplines can work together effectively, while retaining their professional identities and fostering developments in their disciplines. Specifically, I propose the establishment of Institutes of Drug Discovery and Development, whose activities could include development and implementation of a translational pharmacology research strategy, drawing on the collective expertise of the membership and the university as whole; provision of a forum for regular seminars and symposia to promote the discipline, encourage collaboration and develop a cohesive community; provision of a research advisory service, covering, for example, data management, applications for ethics permission, clinical trials design, statistics and regulatory affairs; liaison with potential funders and leadership of major funding bids, including funding for doctoral training; provision of advice on intellectual property protection and the commercialization of research; liaison with corporate partners to facilitate collaboration, knowledge transfer and effective translation; and leadership of undergraduate and postgraduate education in basic and clinical pharmacology and related sciences for medical and science students, including continuing professional development and transferable skills. PMID:22360628

  18. Pharmacological disruption of maladaptive memory.

    PubMed

    Taylor, Jane R; Torregrossa, Mary M

    2015-01-01

    Many psychiatric disorders are characterized by intrusive, distracting, and disturbing memories that either perpetuate the illness or hinder successful treatment. For example, posttraumatic stress disorder (PTSD) involves such strong reemergence of memories associated with a traumatic event that the individual feels like the event is happening again. Furthermore, drug addiction is characterized by compulsive use and repeated relapse that is often driven by internal memories of drug use and/or by exposure to external stimuli that were associated with drug use. Therefore, identifying pharmacological methods to weaken the strength of maladaptive memories is a major goal of research efforts aimed at finding new treatments for these disorders. The primary mechanism by which memories could be pharmacologically disrupted or altered is through manipulation of memory reconsolidation. Reconsolidation occurs when an established memory is remembered or reactivated, reentering a labile state before again being consolidated into long-term memory storage. Memories are subject to disruption during this labile state. In this chapter we will discuss the preclinical and clinical studies identifying potential pharmacological methods for disrupting the integrity of maladaptive memory to treat mental illness. PMID:25977090

  19. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

    PubMed Central

    Čolović, Mirjana B; Krstić, Danijela Z; Lazarević-Pašti, Tamara D; Bondžić, Aleksandra M; Vasić, Vesna M

    2013-01-01

    Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases. PMID:24179466

  20. [Pharmacological preconditioning in carotid endarterectomy].

    PubMed

    Kuznetsov, M R; Karalkin, A V; Fedin, A I; Virganskii, A O; Kunitsyn, N V; Kholopova, E A; Yumin, S M

    2015-01-01

    The study was aimed at examining efficacy of preoperative preparation (pharmacological preconditioning) for carotid endarterectomy in patients with chronic cerebrovascular insufficiency. For this purpose, we analysed the outcomes of surgical treatment in a total of 80 patients presenting with haemodynamically significant unilateral and bilateral lesions of carotid arteries. Of these, 40 patients were operated on immediately and a further 40 patients underwent surgery after pharmacological preconditioning with Actovegin taken at a daily dose of 1,200 mg for 1.5 months. It was demonstrated that preoperative preparation prior to surgery increases cerebral perfusion which is determined by means of single-photon emission computed tomography, thus substantially improving the outcomes of surgical treatment. Statistically significant differences in cognitive function of these groups of patients were revealed 7 days and 6 months after the operation. Improvement of cognitive functions was associated with fewer symptom-free postoperative cerebral ischaemic foci in various regions of the brain. A conclusion was made on a positive role of pharmacological preconditioning with Actovegin in surgical management of cerebrovascular insufficiency, first of all in relation to more complete restoration of cognitive functions. PMID:26355920

  1. Pharmacological and nonpharmacological management of delirium in critically ill patients.

    PubMed

    Hipp, Dustin M; Ely, E Wesley

    2012-01-01

    Delirium is a common yet under-diagnosed syndrome of acute brain dysfunction, which is characterized by inattention, fluctuating mental status, altered level of consciousness, or disorganized thinking. Although our recognition of risk factors for delirium has progressed, our understanding of the underlying pathophysiologic mechanisms remains limited. Improvements in monitoring and assessment for delirium (particularly in the intensive care setting) have resulted in validated and reliable tools such as arousal scales and bedside delirium monitoring instruments. Once delirium is recognized and the modifiable risk factors are addressed, the next step in management (if delirium persists) is often pharmacological intervention. The sedatives, analgesics, and hypnotics most often used in the intensive care unit (ICU) to achieve patient comfort are all too frequently deliriogenic, resulting in a longer duration of ICU and hospital stay, and increased costs. Therefore, identification of safe and efficacious agents to reduce the incidence, duration, and severity of ICU delirium is a hot topic in critical care. Recognizing that there are no medications approved by the Food and Drug Administration (FDA) for the prevention or treatment of delirium, we chose anti-psychotics and alpha-2 agonists as the general pharmacological focus of this article because both were subjects of relatively recent data and ongoing clinical trials. Emerging pharmacological strategies for addressing delirium must be combined with nonpharmacological approaches (such as daily spontaneous awakening trials and spontaneous breathing trials) and early mobility (combined with the increasingly popular approach called: Awakening and Breathing Coordination, Delirium Monitoring, Early Mobility, and Exercise [ABCDE] of critical care) to develop evidence-based approaches that will ensure safer and faster recovery of the sickest patients in our healthcare system. PMID:22270810

  2. Clinical pharmacology of bimatoprost.

    PubMed

    Cantor, Louis B

    2005-06-01

    Bimatoprost (Lumigan), Allergan) is a highly efficacious ocular hypotensive agent that provides good diurnal control of intraocular pressure in glaucoma and ocular hypertensive patients. Bimatoprost is a synthetic molecule that is structurally and pharmacologically similar to prostamide F(2), and appears to mimic the activity of the prostamides. Consistent with prostamide-mimetic activity, bimatoprost has potent inherent pharmacological activity in prostamide-sensitive preparations and essentially remains intact in the living primate eye. This is sufficient to explain its potent and efficacious ocular hypotensive activity, and suggests that bimatoprost is a pharmacologically unique compound. PMID:16922657

  3. A Network Pharmacology Approach to Determine Active Compounds and Action Mechanisms of Ge-Gen-Qin-Lian Decoction for Treatment of Type 2 Diabetes

    PubMed Central

    Li, Huiying; Zhao, Linhua; Zhang, Bo; Jiang, Yuyu; Wang, Xu; Guo, Yun; Liu, Hongxing; Li, Shao; Tong, Xiaolin

    2014-01-01

    Traditional Chinese medicine (TCM) herbal formulae can be valuable therapeutic strategies and drug discovery resources. However, the active ingredients and action mechanisms of most TCM formulae remain unclear. Therefore, the identification of potent ingredients and their actions is a major challenge in TCM research. In this study, we used a network pharmacology approach we previously developed to help determine the potential antidiabetic ingredients from the traditional Ge-Gen-Qin-Lian decoction (GGQLD) formula. We predicted the target profiles of all available GGQLD ingredients to infer the active ingredients by clustering the target profile of ingredients with FDA-approved antidiabetic drugs. We also applied network target analysis to evaluate the links between herbal ingredients and pharmacological actions to help explain the action mechanisms of GGQLD. According to the predicted results, we confirmed that a novel antidiabetic ingredient from Puerariae Lobatae radix (Ge-Gen), 4-Hydroxymephenytoin, increased the insulin secretion in RIN-5F cells and improved insulin resistance in 3T3-L1 adipocytes. The network pharmacology strategy used here provided a powerful means for identifying bioactive ingredients and mechanisms of action for TCM herbal formulae, including Ge-Gen-Qin-Lian decoction. PMID:24527048

  4. Integrating Behavioral and Pharmacological Therapeutic Modalities

    PubMed Central

    Dworkin, Samuel F.

    1986-01-01

    Fear of dental procedures and associated anxiety are widely accepted as important deterents to optimal oral health. Such health care-related fears and anxieties are also common in many areas of medicine. For both medical and dental care a large body of psychologically derived therapeutic modalities have evolved. These methods have been shown to interact positively with pharmacological therapies also designed to help patients better tolerate medical and dental treatment. Despite these findings, behavioral interventions have not found widespread acceptance in medical and dental practice. A multidimensional model which emphasizes the simultaneous consideration of pharmacologic, psychologic, and clinical dental factors is suggested in order to arrive at therapeutic decisions. Further research could address more powerful behavioral modalities, safer pharmacologic methods, and behavioral and pharmacologic combinations which interact optimally for particular clinical conditions. PMID:3458386

  5. Enzymatic Vitrectomy and Pharmacologic Vitreodynamics.

    PubMed

    Shah, Ankoor R; Trese, Michael T

    2016-01-01

    The field of vitreoretinal surgery has evolved substantially over the last several decades. Scientific advances have improved our understanding of disease pathophysiology, and new surgical adjuncts and techniques have decreased surgical time and improved patient outcomes. Pharmacologic agents have recently been developed for intraocular use in order to enhance vitreous removal and even as a nonsurgical treatment for pathology due to an abnormal vitreoretinal interface. Plasmin can successfully cause vitreous liquefaction and induce a posterior vitreous detachment. Additionally, ocriplasmin has been approved for symptomatic vitreomacular adhesion and others appear to be promising for pharmacologic manipulation of the vitreous. The ability to induce vitreous liquefaction and a complete posterior vitreous detachment (PVD) with a single intravitreal injection has potential implications for the management of multiple vitreoretinopathies. Enzymatic vitrectomy may help to reduce vitreous viscosity, thereby facilitating removal during vitrectomy and reducing surgical time, especially when using smaller-gauge vitrectomy instruments. The induction of a PVD also has the potential to reduce intraoperative complications. As we improve our understanding of the molecular flux in the vitreous cavity, pharmacologic vitreodynamics will likely become more important as it may allow for improved manipulation of intravitreal molecules. PMID:26501959

  6. Pharmacotherapy of Traumatic Brain Injury: State of the Science and the Road Forward: Report of the Department of Defense Neurotrauma Pharmacology Workgroup

    PubMed Central

    Kochanek, Patrick M.; Bergold, Peter; Kenney, Kimbra; Marx, Christine E.; Grimes, Col. Jamie B.; Loh, LTC Yince; Adam, LTC Gina E.; Oskvig, Devon; Curley, Kenneth C.; Salzer, Col. Wanda

    2014-01-01

    Abstract Despite substantial investments by government, philanthropic, and commercial sources over the past several decades, traumatic brain injury (TBI) remains an unmet medical need and a major source of disability and mortality in both developed and developing societies. The U.S. Department of Defense neurotrauma research portfolio contains more than 500 research projects funded at more than $700 million and is aimed at developing interventions that mitigate the effects of trauma to the nervous system and lead to improved quality of life outcomes. A key area of this portfolio focuses on the need for effective pharmacological approaches for treating patients with TBI and its associated symptoms. The Neurotrauma Pharmacology Workgroup was established by the U.S. Army Medical Research and Materiel Command (USAMRMC) with the overarching goal of providing a strategic research plan for developing pharmacological treatments that improve clinical outcomes after TBI. To inform this plan, the Workgroup (a) assessed the current state of the science and ongoing research and (b) identified research gaps to inform future development of research priorities for the neurotrauma research portfolio. The Workgroup identified the six most critical research priority areas in the field of pharmacological treatment for persons with TBI. The priority areas represent parallel efforts needed to advance clinical care; each requires independent effort and sufficient investment. These priority areas will help the USAMRMC and other funding agencies strategically guide their research portfolios to ensure the development of effective pharmacological approaches for treating patients with TBI. PMID:23968241

  7. Croatian Meteor Network: ongoing work 2014 - 2015

    NASA Astrophysics Data System (ADS)

    Šegon, D.; Andreić, Ž.; Korlević, K.; Vida, D.

    2015-01-01

    Ongoing work mainly between 2014-2015 International Meteor Conferences (IMC) has been presented. Current sky coverage, software updates, orbit catalogues updates, shower search updates, international collaboration as well as new fields of research and educational efforts made by the Croatian Meteor Network are described.

  8. Overview of Ongoing NRMRL GI Research

    EPA Science Inventory

    This presentation is an overview of ongoing NRMRL Green Infrastructure research and addresses the question: What do we need to know to present a cogent estimate of the value of Green Infrastructure? Discussions included are: stormwater well study, rain gardens and permeable su...

  9. 12 CFR 238.66 - Ongoing requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 4 2012-01-01 2012-01-01 false Ongoing requirements. 238.66 Section 238.66 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) SAVINGS AND LOAN HOLDING COMPANIES (REGULATION LL) Financial Holding Company Activities §...

  10. 12 CFR 238.66 - Ongoing requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Ongoing requirements. 238.66 Section 238.66 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) SAVINGS AND LOAN HOLDING COMPANIES (REGULATION LL) Financial Holding Company Activities §...

  11. 12 CFR 238.66 - Ongoing requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Ongoing requirements. 238.66 Section 238.66 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) SAVINGS AND LOAN HOLDING COMPANIES (REGULATION LL) Financial Holding Company Activities §...

  12. Croatian Meteor Network: Ongoing work 2015 - 2016

    NASA Astrophysics Data System (ADS)

    Šegon, D.; Vida, D.; Korlević, K.; Andreić, Ž.

    2016-01-01

    Ongoing work of the Croatian Meteor Network (CMN) between the 2015 and 2016 International Meteor Conferences is presented. The current sky coverage is considered, software updates and updates of orbit catalogues are described. Furthermore, the work done on meteor shower searches, international collaborations as well as new fields of research are discussed. Finally, the educational efforts made by the CMN are described.

  13. A Network Pharmacology Approach to Understanding the Mechanisms of Action of Traditional Medicine: Bushenhuoxue Formula for Treatment of Chronic Kidney Disease

    PubMed Central

    Zheng, Xiao-yong; Cao, Dong-sheng; Ye, Fa-qing; Xiang, Zheng

    2014-01-01

    Traditional Chinese medicine (TCM) has unique therapeutic effects for complex chronic diseases. However, for the lack of an effective systematic approach, the research progress on the effective substances and pharmacological mechanism of action has been very slow. In this paper, by incorporating network biology, bioinformatics and chemoinformatics methods, an integrated approach was proposed to systematically investigate and explain the pharmacological mechanism of action and effective substances of TCM. This approach includes the following main steps: First, based on the known drug targets, network biology was used to screen out putative drug targets; Second, the molecular docking method was used to calculate whether the molecules from TCM and drug targets related to chronic kidney diseases (CKD) interact or not; Third, according to the result of molecular docking, natural product-target network, main component-target network and compound-target network were constructed; Finally, through analysis of network characteristics and literature mining, potential effective multi-components and their synergistic mechanism were putatively identified and uncovered. Bu-shen-Huo-xue formula (BSHX) which was frequently used for treating CKD, was used as the case to demonstrate reliability of our proposed approach. The results show that BSHX has the therapeutic effect by using multi-channel network regulation, such as regulating the coagulation and fibrinolytic balance, and the expression of inflammatory factors, inhibiting abnormal ECM accumulation. Tanshinone IIA, rhein, curcumin, calycosin and quercetin may be potential effective ingredients of BSHX. This research shows that the integration approach can be an effective means for discovering active substances and revealing their pharmacological mechanisms of TCM. PMID:24598793

  14. Pharmacology of sexually compulsive behavior.

    PubMed

    Codispoti, Victoria L

    2008-12-01

    In a meta-analysis on controlled outcomes evaluations of 22,000 sex offenders, Losel and Schmucker found 80 comparisons between treatment and control groups. The recidivism rate averaged 19% in treated groups, and 27% in controls. Most other reviews reported a lower rate of sexual recidivism in treated sexual offenders. Of 2039 citations in this study (including literature in five languages), 60 studies held independent comparisons. Problematic issues included the control groups; various hormonal, surgical, cognitive behavioral, and psychotherapeutic treatments; and sample sizes. In the 80 studies compared after the year 2000, 32% were reported after 2000, 45% originated in the United States, 45% were reported in journals, and 36% were unpublished. Treatment characteristics showed a significant lack of pharmacologic treatment (7.5%), whereas use cognitive and classical behavioral therapy was 64%. In 68% of the studies, no information was available on the integrity of the treatment implementation; 36% of the treatment settings were outpatient only, 31% were prison settings, and 12% were mixed settings (prison, hospital, and outpatient). Integrating research interpretations is complicated by the heterogeneity of sex offenders, with only 56% being adult men and 17.5% adolescents. Offense types reported included 74% child molestation, 48% incest, and 30% exhibitionism. Pedophilia was not singled out. Follow-up periods varied from 12 months to greater than 84 months. The definition of recidivism ran the gamut from arrest (24%), conviction (30%), charges (19%), and no indication (16%). Results were difficult to interpret because of the methodological problems with this type of study. Overall, a positive outcome was noted with sex offender treatment. Cognitive-behavioral and hormonal treatment were the most promising. Voluntary treatment led to a slightly better outcome than mandatory participation. When accounting for a low base rate of sexual recidivism, the reduction

  15. [SQUALENE: PHYSIOLOGICAL AND PHARMACOLOGICAL PROPERTIES].

    PubMed

    Muzalevskaya, E N; Miroshnichenko, L A; Nikolaevskii, V A; Ushakov, I B; Chernov, Yu N; Alabovskii, V V; Batishcheva, G A; Buzlama, A V

    2015-01-01

    The review of literature demonstrates that squalene, known to most experts as an intermediate product in the synthesis of cholesterol, has several pharmacological properties including hypolipidemic, hepatoprotective, cardioprotective, antioxidant, and antitoxicant activity. Squalene is effective in the treatment of diabetes mellitus type 2 and can potentiate the activity of some antitumor (antiblastoma) preparations and reduce their undesired side effects. This bioactive substance has low toxicity and, in therapeutic doses, does not produce any damaging action on the human organism. A promising source of raw material for the commercial production of squalene is offered by amaranth seed oil. PMID:26292512

  16. Novel pharmacological therapies for irritable bowel syndrome.

    PubMed

    Corsetti, Maura; Whorwell, Peter

    2016-07-01

    Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder, which represents a major cost to healthcare services. Current pharmacological treatment includes fibre supplements, antispasmodics, laxatives, loperamide and antidepressants. This article reviews the novel pharmacological treatments already or recently approved for patients with IBS-C (lubiprostone, linaclotide) and IBS-D (alosetron, ramosetron, rifaximin, eluxadoline). Furthermore, results for drugs in development (plecanatide, ibudutant and ebastine) or used in chronic constipation or for other indications, with potential application in IBS (prucalopride, elobixibat, mesalazine, ondansetron and colesevelam) are also reviewed. PMID:26907518

  17. Pharmacologic agents for mucus clearance in bronchiectasis.

    PubMed

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis. PMID:22640851

  18. A pathogenic mechanism of chronic ongoing myocarditis.

    PubMed

    Nakamura, H; Yamamura, T; Fukuta, S; Matsumori, A; Matsuzaki, M

    1996-08-01

    To clarify the pathogenetic mechanism of chronic ongoing myocarditis, we produced Coxsackievirus B3-induced myocarditis in A/J mice and immunopathologically examined the microcirculation in the chronic phase of myocarditis. Forty-two 3-week-old A/J mice were inoculated intraperitoneally with Coxsackievirus B3 (Nancy strain) 2 x 10(4) PFU (plaque-forming units) and sacrificed 7, 14, 21, 50, 90, or 120 days later. To evaluate myocardial microcirculation, 18 of the hearts were perfused from the thoracic aorta with warm 2% gelatin/carbon solution. The remaining hearts were quickly frozen for immunologic analysis with an enzyme immunostaining assay using monoclonal antibodies against CD4, CD8, macrophages, intercellular