Pathogenesis of Nonsteroidal Anti-Inflammatory Drug Gastropathy: Clues to Preventative Therapy

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Salim MA Bastaki

1999-01-01

Full Text Available Gastric ulceration and bleeding are major impediments to the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs. The development of effective therapies for prevention of these adverse effects requires better understanding of their pathogenesis. Several features of NSAIDs contribute to the development of damage in the stomach, including the topical irritant effects of these drugs on the epithelium, impairment of the barrier properties of the mucosa, suppression of gastric prostaglandin synthesis, reduction of gastric mucosal blood flow and interference with the repair of superficial injury. The presence of acid in the lumen of the stomach also contributes to the pathogenesis of NSAID-induced ulcers and bleeding in a number of ways. Acid impairs the restitution process, interferes with hemostasis and can inactivate several growth factors that are important in mucosal integrity and repair. Profound suppression of gastric acid secretion has been shown to be effective in preventing NSAID-induced ulceration. There is a strong possibility that new NSAIDs entering the market will have greatly reduced toxicity in the gastrointestinal tract.

A short history of anti-rheumatic therapy. III. Non steroidal anti-inflammatory drugs

Directory of Open Access Journals (Sweden)

P. Marson

2011-06-01

Full Text Available The chemical advances of the 20th century led to the synthesis of non steroidal anti-inflammatory drugs (NSAIDs, beginning from phenylbutazone and indomethacin and continuing with other new drugs, including ibuprofen, diclofenac, naproxen, piroxicam and, more recently, the highly selective COX-2 inhibitors (coxibs. This progress derived from the discovery of the mechanism of action of these drugs: the inhibition of synthesis of prostaglandins due to the cycloxigenase enzyme system, according to the experimental contributions of John R. Vane.

Quantity and economic value of unused oral anti-cancer and biological disease-modifying anti-rheumatic drugs among outpatient pharmacy patients who discontinue therapy.

Science.gov (United States)

Bekker, C L; Melis, E J; Egberts, A C G; Bouvy, M L; Gardarsdottir, H; van den Bemt, B J F

2018-03-24

Patients sometimes discontinue the use of expensive oral anti-cancer drug (OACD) or biological disease-modifying anti-rheumatic drug (bDMARD) therapies early, leading to medication waste if the patient has not used all dispensed medication. To determine the proportion of patients who have unused OACDs or bDMARDs after therapy discontinuation, and the quantity and economic value of these unused medications. Furthermore, patients' reasons for therapy discontinuation and their disposal method for unused medications were determined. In a retrospective follow-up study using a Dutch outpatient pharmacy database, patients (≥18 years) who did not refill an OACD or bDMARD prescription, dispensed between November 2015 and February 2016, within two weeks of the prescription end date were contacted by phone and asked about their unused medication and reasons thereof. The economic value was calculated using Dutch medication prices. Data were descriptively analyzed in STATA13. The database included 1173 patients, of whom 159 likely had discontinued therapy and were contacted. Of these, 88 patients were excluded (39 refilled, 47 missing, and 2 other). Of the 71 patients who had discontinued therapy, 39 (54.9%) had unused medications, comprising 22 OACD users (mean age 63.0 (SD ± 15.9) years, 50.0% female) and 17 bDMARD users (mean age 50.7 (SD ± 13.5) years, 47.1% female). A total of 59 packages were unused, with a total value of €60,341. Unused OACD packages and bDMARD packages had median values of €179 (IQR €24-2487) and €992 (IQR €681-1093), respectively. Patients primarily discontinued therapy due to adverse or insufficient effects. This study illustrates that more than half of patients discontinuing OACD or bDMARD therapies have unused medication. This emphasizes the need for waste-reducing interventions. Copyright © 2018 Elsevier Inc. All rights reserved.

Parkinsonian signs are a risk factor for falls.

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Dahodwala, Nabila; Nwadiogbu, Chinwe; Fitts, Whitney; Partridge, Helen; Karlawish, Jason

2017-06-01

Parkinsonian signs are common, non-specific findings in older adults and associated with increased rates of dementia and mortality. It is important to understand which motor outcomes are associated with parkinsonian signs. To determine the role of parkinsonian signs on fall rates among older adults. We conducted a longitudinal study of primary care patients from the University of Pennsylvania Health System. Adults over 55 years were assessed at baseline through surveys and a neurological examination. We recorded falls over the following 2 years. Parkinsonian signs were defined as the presence of 2 of 4 cardinal signs. Incident falls were compared between subjects with and without parkinsonian signs, and modified Poisson regression used to adjust for potential confounders in the relationship between parkinsonian signs and falls. 982 subjects with a mean age of 68 (s.d. 8.8) years participated. 29% of participants fell and 12% exhibited parkinsonian signs at baseline. The unadjusted RR for falls among individuals with parkinsonian signs was 1.36 (95% CI 1.05-1.76, p=0.02). After adjusting for age, cognitive function, urinary incontinence, depression, diabetes, stroke and arthritis, individuals with parkinsonian signs were still 38% more likely to fall than those without parkinsonian signs (RR 1.38, 95% CI 1.04-1.82; p=0.03). Falls among those with parkinsonian signs were more likely to lead to injury (53% vs 37%; p=0.04). Parkinsonian signs are a significant, independent risk factor for falls. Early detection of this clinical state is important in order to implement fall prevention programs among primary care patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Osteoarthritis guidelines: a progressive role for topical nonsteroidal anti-inflammatory drugs

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Stanos SP

2013-04-01

Full Text Available Steven P Stanos Rehabilitation Institute of Chicago, Center for Pain Management, Chicago, IL, USA Abstract: Current treatment guidelines for the treatment of chronic pain associated with osteoarthritis reflect the collective clinical knowledge of international experts in weighing the benefits of pharmacologic therapy options while striving to minimize the negative effects associated with them. Consideration of disease progression, pattern of flares, level of functional impairment or disability, response to treatment, coexisting conditions such as cardiovascular disease or gastrointestinal disorders, and concomitant prescription medication use should be considered when creating a therapeutic plan for a patient with osteoarthritis. Although topical nonsteroidal anti-inflammatory drugs historically have not been prevalent in many of the guidelines for osteoarthritis treatment, recent evidence-based medicine and new guidelines now support their use as a viable option for the clinician seeking alternatives to typical oral formulations. This article provides a qualitative review of these treatment guidelines and the emerging role of topical nonsteroidal anti-inflammatory drugs as a therapy option for patients with localized symptoms of osteoarthritis who may be at risk for oral nonsteroidal anti-inflammatory drug-related serious adverse events. Keywords: osteoarthritis, nonsteroidal anti-inflammatory drugs, guidelines, topical analgesics, diclofenac

Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

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Avinaba Mukherjee

2016-03-01

Full Text Available Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the ‘apicoplast’, which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle’s function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug

Animal models for testing anti-prion drugs.

Science.gov (United States)

Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín

2013-01-01

Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.

[Anti-angiogenic drugs].

Science.gov (United States)

Sato, Yasufumi

2010-06-01

Angiogenesis or neovascularization, the formation of neo-vessels, is a physiological phenomenon endued in vasculature, but is involved in various pathological conditions. Angiogenesis is required for tumor growth and metastasis, and thus constitutes an important target for the control of tumor progression. Indeed, the recent development of bevacizumab, a neutralizing anti-VEGF monoclonal antibody as the first anti-angiogenic drug, legalized the clinical merit of anti-angiogenesis in cancers. Thereafter, various drugs targeting VEGF-mediated signals have been developed to control tumor angiogenesis. Thus, anti-angiogenic drugs are now recognized in the clinic as a major step forward for the treatment of cancers. This review focuses on the current status of antiangiogenesis treatment in cancers.

Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis

DEFF Research Database (Denmark)

Ahlehoff, O; Skov, L; Gislason, G

2014-01-01

BACKGROUND: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients...... with severe psoriasis treated with systemic anti-inflammatory drugs. METHODS: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence...... intervals (CIs) of cardiovascular events associated with use of biological drugs, methotrexate, cyclosporine, retinoids and other antipsoriatic therapies, including topical treatments, phototherapy and climate therapy. RESULTS: A total of 6902 patients (9662 treatment exposures) with a maximum follow...

Adjuvant Anti-Angiogenesis Drugs Are No Benefit in Kidney Cancer

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Results from a recent clinical trial show that post-surgical therapy with two anti-angiogenesis drugs does not improve progression-free survival for patients with kidney cancer and may cause serious side effects.

Osteoarthritis guidelines: a progressive role for topical nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Stanos, Steven P

2013-01-01

Current treatment guidelines for the treatment of chronic pain associated with osteoarthritis reflect the collective clinical knowledge of international experts in weighing the benefits of pharmacologic therapy options while striving to minimize the negative effects associated with them. Consideration of disease progression, pattern of flares, level of functional impairment or disability, response to treatment, coexisting conditions such as cardiovascular disease or gastrointestinal disorders, and concomitant prescription medication use should be considered when creating a therapeutic plan for a patient with osteoarthritis. Although topical nonsteroidal anti-inflammatory drugs historically have not been prevalent in many of the guidelines for osteoarthritis treatment, recent evidence-based medicine and new guidelines now support their use as a viable option for the clinician seeking alternatives to typical oral formulations. This article provides a qualitative review of these treatment guidelines and the emerging role of topical nonsteroidal anti-inflammatory drugs as a therapy option for patients with localized symptoms of osteoarthritis who may be at risk for oral nonsteroidal anti-inflammatory drug-related serious adverse events.

The emergence of two anti-phase oscillatory neural populations in a computational model of the Parkinsonian globus pallidus

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Robert John Merrison-Hort

2013-12-01

Full Text Available Experiments in rodent models of Parkinson's Disease have demonstrated a prominent increase of oscillatory firing patterns in neurons within the Parkinsonian globus pallidus (GP which may underlie some of the motor symptoms of the disease. There are two main pathways from the cortex to GP: via the striatum and via the subthalamic nucleus (STN, but it is not known how these inputs sculpt the pathological pallidal firing patterns. To study this we developed a novel neural network model of conductance-based spiking pallidal neurons with cortex-modulated input from STN neurons. Our results support the hypothesis that entrainment occurs primarily via the subthalamic pathway. We find that as a result of the interplay between excitatory input from the STN and mutual inhibitory coupling between GP neurons, a homogeneous population of GP neurons demonstrates a self-organising dynamical behaviour where two groups of neurons emerge: one spiking in-phase with the cortical rhythm and the other in anti-phase. This finding mirrors what is seen in recordings from the GP of rodents that have had Parkinsonism induced via brain lesions. Our model also includes downregulation of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN channels in response to burst firing of GP neurons, since this has been suggested as a possible mechanism for the emergence of Parkinsonian activity. We found that the downregulation of HCN channels provides even better correspondence with experimental data but that it is not essential in order for the two groups of oscillatory neurons to appear. We discuss how the influence of inhibitory striatal input will strengthen our results.

Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK

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Taek-In Oh

2017-12-01

Full Text Available Fascaplysin, a natural product isolated from marine sponges, is a potential candidate for the development of anti-cancer drugs. However, the mechanism underlying its therapeutic effect of strengthening anti-cancer efficacy of other drugs is poorly understood. Here, we found that fascaplysin increases phosphorylation of protein kinase B (PKB, also known as AKT, and adenosine monophosphate-activated protein kinase (AMPK, which are considered therapeutic targets for cancer treatment due to their anti-apoptotic or pro-survival functions in cancer. A cell viability assay revealed that pharmacological suppression of AKT using LY294002 enhanced the anti-cancer effect of fascaplysin in various cancer cells. Similarly, fascaplysin was observed to have improved anti-cancer effects in combination with compound C, a selective AMPK inhibitor. Another challenge showed that fascaplysin increased the efficacy of methotrexate (MTX-mediated cancer therapy by suppressing genes related to folate and purine metabolism. Overall, these results suggest that fascaplysin may be useful for improving the anti-cancer efficacy of targeted anti-cancer drugs, such as inhibitors of phosphoinositide 3-kinase AKT signaling, and chemotherapeutic agents, such as MTX.

Biomarkers for Anti-Angiogenic Therapy in Cancer

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Markus Wehland

2013-04-01

Full Text Available Angiogenesis, the development of new vessels from existing vasculature, plays a central role in tumor growth, survival, and progression. On the molecular level it is controlled by a number of pro- and anti-angiogenic cytokines, among which the vascular endothelial growth factors (VEGFs, together with their related VEGF-receptors, have an exceptional position. Therefore, the blockade of VEGF signaling in order to inhibit angiogenesis was deemed an attractive approach for cancer therapy and drugs interfering with the VEGF-ligands, the VEGF receptors, and the intracellular VEGF-mediated signal transduction were developed. Although promising in pre-clinical trials, VEGF-inhibition proved to be problematic in the clinical context. One major drawback was the generally high variability in patient response to anti-angiogenic drugs and the rapid development of therapy resistance, so that, in total, only moderate effects on progression-free and overall survival were observed. Biomarkers predicting the response to VEGF-inhibition might attenuate this problem and help to further individualize drug and dosage determination. Although up to now no definitive biomarker has been identified for this purpose, several candidates are currently under investigation. This review aims to give an overview of the recent developments in this field, focusing on the most prevalent tumor species.

Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.

Science.gov (United States)

Kumar, Santosh; Rao, P S S; Earla, Ravindra; Kumar, Anil

2015-03-01

Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse.

A short history of anti-rheumatic therapy. II. Aspirin

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P. Marson

2011-06-01

Full Text Available The discovery of aspirin, an antipyretic, anti-inflammatory and analgesic drug, undoubtedly represents a milestone in the history of medical therapy. Since ancient times the derivatives of willow (Salix alba were used to treat a variety of fevers and pain syndromes, although the first report dates back to 1763 when the English Reverend Edward Stone described the effect of an extract of the bark willow in treating malaria. In the XIX century many apothecaries and chemists, including the Italian Raffaele Piria and Cesare Bertagnini, developed the biological processes of extraction and chemical synthesis of salicylates, and then analyzed their therapeutic properties and pharmacokinetic and pharmacodynamic characteristics. In 1899 the Bayer Company, where Felix Hoffmann, Heinrich Dreser and Arthur Eichengrün worked, recorded acetyl-salicylic acid under the name “Aspirin”. In the XX century, besides the definition of the correct applications of aspirin in the anti-rheumatic therapy being defined, Lawrence L. Crawen identified the property of this drug as an anti-platelet agent, thus opening the way for more widespread uses in cardiovascular diseases.

Substandard anti-malarial drugs in Burkina Faso

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Sie Ali

2008-05-01

Full Text Available Abstract Background There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries. Methods A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers and illicit (market and street vendors, shops sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation. Results Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50% chloroquine, 10/77 (13% pyrimethamine-sulphadoxine, 9/77 (12% quinine, 6/77 (8% amodiaquine, 9/77 (12% artesunate, and 4/77 (5% artemether-lumefantrine. 32/77 (42% drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6% and 27/30 (90.0% samples of substandard drugs respectively. Conclusion These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the

Anti-thyroid drugs in pediatric Graves′ disease

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Mathew John

2015-01-01

Full Text Available Graves′ disease is the most common cause of hyperthyroidism in children. Most children and adolescents are treated with anti-thyroid drugs as the initial modality. Studies have used Methimazole, Carbimazole and Propylthiouracil (PTU either as titration regimes or as block and replacement regimes. The various studies of anti-thyroid drug (ATD treatment of Graves′ disease in pediatric patients differ in terms of the regimes, remission rate, duration of therapy for adequate remission, follow up and adverse effects of ATD. Various studies show that lower thyroid hormone levels, prolonged duration of treatment, lower levels of TSH receptor antibodies, smaller goiter and increased age of child predicted higher chance of remission after ATD. A variable number of patients experience minor and major adverse effects limiting initial and long term treatment with ATD. The adverse effects of various ATD seem to more in children compared to that of adults. In view of liver injury including hepatocellular failure need of liver transplantation associated with PTU, the use has been restricted in children. The rate of persistent remission with ATD following discontinuation is about 30%. Radioactive iodine therapy is gaining more acceptance in older children with Graves′s disease in view of the limitations of ATD. For individual patients, risk-benefit ratio of ATD should be weighed against benefits of radioactive iodine therapy and patient preferences.

Graves' disease in a 3 year-old patient with agranulocytosis due to anti-thyroid drugs: Radioiodine ablation therapy as an effective alternative.

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Espinosa-Muñoz, E; Ramírez-Ocaña, D; Martín-García, A M; Ruiz-García, F J; Puentes-Zarzuela, C

The case is presented of a 3 year-old girl with mitochondrial disease (subacute necrotizing encephalomyelopathy of Leigh syndrome), v-stage chronic kidney disease of a diffuse mesangial sclerosis, as well as developmental disorders, and diagnosed with hyperthyroidism Graves-Basedow disease. Six weeks after starting the treatment with neo-carbimazole, the patient reported a serious case of agranulocytosis. This led to stopping the anti-thyroid drugs, and was treated successfully with 131 I ablation therapy. The relevance of the article is that Graves' disease is uncommon in the paediatric age range (especially in children younger than 6 years old), and developing complications due to a possible late diagnosis. Agranulocytosis as a potentially serious adverse effect following the use of anti-thyroid drugs, and the few reported cases of ablation therapy with 131 I at this age, makes this case unique. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Non-invasive imaging for studying anti-angiogenic therapy effects

NARCIS (Netherlands)

Ehling, J.; Lammers, Twan Gerardus Gertudis Maria; Kiessling, F.

2013-01-01

Noninvasive imaging plays an emerging role in preclinical and clinical cancer research and has high potential to improve clinical translation of new drugs. This article summarises and discusses tools and methods to image tumour angiogenesis and monitor anti-angiogenic therapy effects. In this

Nurses' perceptions about Botswana patients' anti-retroviral therapy ...

African Journals Online (AJOL)

Anti-retroviral drugs(ARVs) are supplied free of charge in Botswana. Lifelong adherence to antiretroviral therapy (ART) is vital to improve the patient's state of well-being and to prevent the development of strains of the human immunodefi ciency virus (HIV) that are resistant to ART. Persons with ART-resistant strains of HIV ...

A short history of anti-rheumatic therapy - VI. Rheumatoid arthritis drugs

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G. Pasero

2011-09-01

Full Text Available The treatment of rheumatoid arthritis traditionally includes symptomatic drugs, showing a prompt action on pain and infl ammation, but without any infl uence on disease progression, and other drugs that could modify the disease course and occasionally induce clinical remission (DMARDs or disease modifying anti-rheumatic drugs. This review describes the historical steps that led to the use of the main DMARDs in rheumatoid arthritis, such as gold salts, sulphasalazine, chloroquine and hydroxychloroquine, D-penicillamine, and other immunoactive drugs, including methotrexate, azathioprine, cyclosporin and lefl unomide. The historical evolution of use of these drugs is then discussed, including the strategy of progressive (“therapeutic pyramid” or of more aggressive treatment, through the simultaneous use of two or more DMARDs (“combination therapy”.

Saleability of anti-malarials in private drug shops in Muheza, Tanzania: a baseline study in an era of assumed artemisinin combination therapy (ACT

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Ringsted Frank M

2011-08-01

Full Text Available Abstract Background Artemether-lumefantrine (ALu replaced sulphadoxine-pymimethamine (SP as the official first-line anti-malarial in Tanzania in November 2006. So far, artemisinin combination therapy (ACT is contra-indicated during pregnancy by the national malaria treatment guidelines, and pregnant women depend on SP for Intermittent Preventive Treatment (IPTp during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform a baseline study of the private market for anti-malarials in Muheza town, an area with widespread anti-malarial drug resistance, prior to the implementation of a provider training and accreditation programme that will allow accredited drug shops to sell subsidized ALu. Methods All drug shops selling prescription-only anti-malarials, in Muheza town, Tanga Region voluntarily participated from July to December 2009. Qualitative in-depth interviews were conducted with owners or shopkeepers on saleability of anti-malarials, and structured questionnaires provided quantitative data on drugs sales volume. Results All surveyed drug shops illicitly sold SP and quinine (QN, and legally amodiaquine (AQ. Calculated monthly sale was 4,041 doses, in a town with a population of 15,000 people. Local brands of SP accounted for 74% of sales volume, compared to AQ (13%, QN (11% and ACT (2%. Conclusions In community practice, the saleability of ACT was negligible. SP was best-selling, and use was not reserved for IPTp, as stipulated in the national anti-malarial policy. It is a major reason for concern that such drug-pressure in the community equals de facto intermittent presumptive treatment. In an area where SP drug resistance remains high, unregulated SP dispensing to people other than pregnant women runs the risk of eventually jeopardizing the effectiveness of the IPTp

Clinical outcomes and immune benefits of anti-epileptic drug therapy in HIV/AIDS

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Krentz Hartmut B

2010-06-01

Full Text Available Abstract Background Anti-epileptic drugs (AEDs are frequently prescribed to persons with HIV/AIDS receiving combination antiretroviral therapy (cART although the extent of AED use and their interactions with cART are uncertain. Herein, AED usage, associated toxicities and immune consequences were investigated. Methods HIV replication was analysed in proliferating human T cells during AED exposure. Patients receiving AEDs in a geographically-based HIV care program were assessed using clinical and laboratory variables in addition to assessing AED indication, type, and cumulative exposures. Results Valproate suppressed proliferation in vitro of both HIV-infected and uninfected T cells (p 0.05 but AED exposures did not affect HIV production in vitro. Among 1345 HIV/AIDS persons in active care between 2001 and 2007, 169 individuals were exposed to AEDs for the following indications: peripheral neuropathy/neuropathic pain (60%, seizure/epilepsy (24%, mood disorder (13% and movement disorder (2%. The most frequently prescribed AEDs were calcium channel blockers (gabapentin/pregabalin, followed by sodium channel blockers (phenytoin, carbamazepine, lamotrigine and valproate. In a nested cohort of 55 AED-treated patients receiving cART and aviremic, chronic exposure to sodium and calcium channel blocking AEDs was associated with increased CD4+ T cell levels (p 0.05 with no change in CD8+ T cell levels over 12 months from the beginning of AED therapy. Conclusions AEDs were prescribed for multiple indications without major adverse effects in this population but immune status in patients receiving sodium or calcium channel blocking drugs was improved.

Cognition In Parkinsonian Syndromes : A Review

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Das Sujata

2004-01-01

Full Text Available Parkinson′s disease is a distinctive progressive disorder characterised clinically by tremor, rigidity, bradykinesia and postural imbalance. Although James Parkinson himself denied the presence of intellectual changes in the parkinsonian Disease, thorough exploration has revealed behavioural and cognitive changes to be explicit in the patients. India, along with its demographic shift and its overwhelming population growth, falls a victim to all old-age degenerative diseases. A large percentage of the elderly Indian population today suffers from Parkinsonian and related disorders. Disturbed cognition and neurobehavioral abnormalities are enough reasons for a falling ADL (activities of daily living curve, and consequent distress to families of PD patients. Spontaneous involvement of one and all is required to not only intervene with the right pharmacological therapy, but also to empathize and develop the right attitude towards the affected person. Cognitive dysfunction in Parkinson′s disease is well established and its affection in the early stage has been reported. In this article. We attempt to review and update the various cognitive impairments that occur in all the Parkinson related disorders which necessitates diagnosis, management and rehabilitation to alleviate patients′ suffering. It also reviews the role of frontal lobe, dementia and depression with respect to these patients.

In Silico Identification and In Vitro and In Vivo Validation of Anti-Psychotic Drug Fluspirilene as a Potential CDK2 Inhibitor and a Candidate Anti-Cancer Drug.

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Xi-Nan Shi

Full Text Available Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related deaths worldwide. Surgical resection and conventional chemotherapy and radiotherapy ultimately fail due to tumor recurrence and HCC's resistance. The development of novel therapies against HCC is thus urgently required. The cyclin-dependent kinase (CDK pathways are important and well-established targets for cancer treatment. In particular, CDK2 is a key factor regulating the cell cycle G1 to S transition and a hallmark for cancers. In this study, we utilized our free and open-source protein-ligand docking software, idock, prospectively to identify potential CDK2 inhibitors from 4,311 FDA-approved small molecule drugs using a repurposing strategy and an ensemble docking methodology. Sorted by average idock score, nine compounds were purchased and tested in vitro. Among them, the anti-psychotic drug fluspirilene exhibited the highest anti-proliferative effect in human hepatocellular carcinoma HepG2 and Huh7 cells. We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. We also examined the anti-cancer effect of fluspirilene in vivo in BALB/C nude mice subcutaneously xenografted with human hepatocellular carcinoma Huh7 cells. Our results showed that oral fluspirilene treatment significantly inhibited tumor growth. Fluspirilene (15 mg/kg exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil (10 mg/kg. Moreover, the cocktail treatment with fluspirilene and 5-fluorouracil exhibited the highest therapeutic effect. These results suggested for the first time that fluspirilene is a potential CDK2 inhibitor and a candidate anti-cancer drug for the treatment of human hepatocellular carcinoma. In view of the fact that fluspirilene has a long history

Novel Drug Delivery Technique for Breast Cancer Therapy

National Research Council Canada - National Science Library

Esenaliev, Rinat O

2004-01-01

.... We proposed to complete Task 3 and to implement Task 4 in the third year of the project. Task 3 focuses on in vivo studies of efficacy of cancer therapy with the use of ultrasound-enhanced delivery of anti-cancer drug 5-FU...

[Adherence with proton pump inhibitor therapy, by continuously taking nonsteroidal anti-inflammatory drugs].

Science.gov (United States)

Pimanov, S I; Makarenko, E V; Dikareva, E A

2015-01-01

To estimate the impact of adherence with proton pump inhibitor (PPI) therapy on the incidence of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy (NSAID gastropathy) in patients with rheumatoid arthritis (RA). PPI pharmacotherapy adherence was estimated using the Medication Adherence Questionnaire (MAQ) in 92 patients with RA, including 32 patients did not take a PPI and 60 used a PPI. The groups were matched for age, disease duration, and used NSAIDs. All those asked underwent video esophagogastroduodenoscopy. According to the data of MAQ survey, low, moderate, and high adherence subgroups could be identified among the patients treated with a PPI. NSAID gastropathy was detected in 43.8% of the patients taking no PPI, in 50% of those with low PPI treatment adherence, in 12.5% with moderate adherence, and in 4.5% with high adherence. In the patients with low adherence to PPI therapy, NSAID gastropathy was recorded 11 times more frequently than in those with high adherence (c2 = 7.77; p = 0.005). This condition occurred in 28.6% of the patients taking NSAID without preventively using a PPI in the absence of risk factors for NSAID gastropathy. Only 36.7% patients who had been recommended to use a PPI for the prevention of NSAID gastropathy strictly observed their doctor's directions. Low PPI pharmacotherapy adherence may serve as an additional risk factor for NSAID gastropathy in patients in whom preventive antisecretory therapy used in combination with NSAID is indicated.

Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.

Directory of Open Access Journals (Sweden)

Heewon Park

Full Text Available The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc. and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.

Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes.

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Xu, Yuhui; Wu, Jianan; Liao, Sha; Sun, Zhaogang

2017-10-03

Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts' body weight, metabolic processing of the drug, malabsorption and/or drug-drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen's physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.

Repurposing the Nonsteroidal Anti-inflammatory Drug Diflunisal as an Osteoprotective, Antivirulence Therapy for Staphylococcus aureus Osteomyelitis.

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Hendrix, Andrew S; Spoonmore, Thomas J; Wilde, Aimee D; Putnam, Nicole E; Hammer, Neal D; Snyder, Daniel J; Guelcher, Scott A; Skaar, Eric P; Cassat, James E

2016-09-01

Staphylococcus aureus osteomyelitis is a common and debilitating invasive infection of bone. Treatment of osteomyelitis is confounded by widespread antimicrobial resistance and the propensity of bacteria to trigger pathological changes in bone remodeling that limit antimicrobial penetration to the infectious focus. Adjunctive therapies that limit pathogen-induced bone destruction could therefore limit morbidity and enhance traditional antimicrobial therapies. In this study, we evaluate the efficacy of the U.S. Food and Drug Administration-approved, nonsteroidal anti-inflammatory (NSAID) compound diflunisal in limiting S. aureus cytotoxicity toward skeletal cells and in preventing bone destruction during staphylococcal osteomyelitis. Diflunisal is known to inhibit S. aureus virulence factor production by the accessory gene regulator (agr) locus, and we have previously demonstrated that the Agr system plays a substantial role in pathological bone remodeling during staphylococcal osteomyelitis. Consistent with these observations, we find that diflunisal potently inhibits osteoblast cytotoxicity caused by S. aureus secreted toxins independently of effects on bacterial growth. Compared to commonly used NSAIDs, diflunisal is uniquely potent in the inhibition of skeletal cell death in vitro Moreover, local delivery of diflunisal by means of a drug-eluting, bioresorbable foam significantly limits bone destruction during S. aureus osteomyelitis in vivo Collectively, these data demonstrate that diflunisal potently inhibits skeletal cell death and bone destruction associated with S. aureus infection and may therefore be a useful adjunctive therapy for osteomyelitis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The phenomenology of parkinsonian tremor.

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Deuschl, Günther; Papengut, Frank; Hellriegel, Helge

2012-01-01

The definition of Parkinsonian tremor covers all different forms occurring in Parkinson's disease. The most common form is rest tremor, labelled as typical Parkinsonian tremor. Other variants cover also postural and action tremors. Data support the notion that suppression of rest tremor may be more specific for PD tremors. Several differential diagnoses like rest tremor in ET, dystonic tremor, psychogenic tremor and Holmes' tremor may be misinterpreted as PD-tremor. Tests and clinical clues to separate them are presented. Copyright © 2011 Elsevier Ltd. All rights reserved.

Analysis of glottal source parameters in Parkinsonian speech.

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Hanratty, Jane; Deegan, Catherine; Walsh, Mary; Kirkpatrick, Barry

2016-08-01

Diagnosis and monitoring of Parkinson's disease has a number of challenges as there is no definitive biomarker despite the broad range of symptoms. Research is ongoing to produce objective measures that can either diagnose Parkinson's or act as an objective decision support tool. Recent research on speech based measures have demonstrated promising results. This study aims to investigate the characteristics of the glottal source signal in Parkinsonian speech. An experiment is conducted in which a selection of glottal parameters are tested for their ability to discriminate between healthy and Parkinsonian speech. Results for each glottal parameter are presented for a database of 50 healthy speakers and a database of 16 speakers with Parkinsonian speech symptoms. Receiver operating characteristic (ROC) curves were employed to analyse the results and the area under the ROC curve (AUC) values were used to quantify the performance of each glottal parameter. The results indicate that glottal parameters can be used to discriminate between healthy and Parkinsonian speech, although results varied for each parameter tested. For the task of separating healthy and Parkinsonian speech, 2 out of the 7 glottal parameters tested produced AUC values of over 0.9.

Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development

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Jan eStenvang

2013-12-01

Full Text Available Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs and honing regimens of existing anti-cancer drugs. Although discovery and development of novel and effective anti-cancer drugs is a major research area, it is well known that oncology drug development is a lengthy process, extremely costly and with high attrition rates. Furthermore, those drugs that do make it through the drug development mill are often quite expensive, laden with severe side-effects and, unfortunately, to date, have only demonstrated minimal increases in overall survival. Therefore, a strong interest has emerged to identify approved non-cancer drugs that possess anti-cancer activity, thus shortcutting the development process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible anti-cancer activity, we focus on the discovery of novel cancer indications for already approved chemotherapeutic anti-cancer drugs. Clinical implementation of this strategy is normally commenced at clinical phase II trials and includes pre-treated patients. As the response rates to any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I inhibitors and topoisomerase I as a potential predictive biomarker as case in point.

Role of anti-angiogenesis therapy in the management of hepatocellular carcinoma: The jury is still out

Institute of Scientific and Technical Information of China (English)

Hong; Sun; Man-Sheng; Zhu; Wen-Rui; Wu; Xiang-De; Shi; Lei-Bo; Xu

2014-01-01

As the leading cause of disease-related deaths,cancer is a major public health threat worldwide.Surgical resection is still the first-line therapy for patients with early-stage cancers.However,postoperative relapse and metastasis remain the cause of 90%of deaths of patients with solid organ malignancies,including hepatocellular carcinoma(HCC).With the rapid development of molecular biology techniques in recent years,molecularly targeted therapies using monoclonal antibodies,small molecules,and vaccines have become a milestone in cancer therapeutic by significantly improv-ing the survival of cancer patients,and have opened a window of hope for patients with advanced cancer.Hypervascularization is a major characteristic of HCC.It has been reported that anti-angiogenic treatments,which inhibit blood vessel formation,are highly effective for treating HCC.However,the efficacy and safety of anti-angiogenesis therapies remain controversial.Sorafenib is an oral multikinase inhibitor with antiproliferative and anti-angiogenic effects and is the first molecular target drug approved for the treatment of advanced HCC.While sorafenib has shown promising therapeutic effects,substantial evidence of primary and acquired resistance to sorafenib has been reported.Numerous clinical trials have been conducted to evaluate a large number of molecularly targeted drugs for treating HCC,but most drugs exhibited less efficacy and/or higher toxicity compared to sorafenib.Therefore,understanding the mechanism(s)underlying sorafenib resistance of cancer cells is highlighted for efficiently treating HCC.This concise review aims to provide an overview of anti-angiogenesis therapy in the management of HCC and to discuss the common mechanisms of resistance to anti-angiogenesis therapies.

Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors.

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Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin'ichi; Aoki, Yoshitsugu

2016-01-01

Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD.

Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients

DEFF Research Database (Denmark)

Lødrup, A; Pottegård, A; Hallas, J

2015-01-01

BACKGROUND: Guidelines recommend that patients with gastro-oesophageal reflux disease are adequately treated with acid-suppressive therapy before undergoing anti-reflux surgery. Little is known of the use of acid-suppressive drugs before anti-reflux surgery. AIM: To determine the use of proton pump...... inhibitors and H2 -receptor antagonists in the year before anti-reflux surgery. METHODS: A nationwide retrospective study of all patients aged ≥18 undergoing first-time anti-reflux surgery in Denmark during 2000-2012 using data from three different sources: the Danish National Register of Patients......, the Danish National Prescription Register, and the Danish Person Register. RESULTS: The study population thus included 2922 patients (median age: 48 years, 55.7% male). The annual proportion of patients redeeming ≥180 DDD of acid-suppressive therapy increased from 17.0% 5 years before anti-reflux surgery...

[Anti-rheumatic therapy in patients with rheumatoid arthritis undergoing hemodialysis].

Science.gov (United States)

Akiyama, Yuji

2011-01-01

Hemodialysis (HD) patients have been increasing recently. Some rheumatoid arthritis (RA) patients need hemodialysis (HD), though the proportion is not high. At present, such patients are almost treated with corticosteroids and/or nonsteroidal anti-inflammatory drugs alone, even if they have a high disease activity that would require disease-modifying anti-rheumatic drug (DMARD) therapy, partly because the safety of DMARDs in RA patients with end-stage renal disease has not been confirmed. Their joint destruction would be inevitable and lead to impaired activities of daily living. As there are no guidelines for the use of DMARDs in HD patients, here I reviewed the previous reports about the treatment of DMARDs including biologics for patients with RA undergoing HD.

Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Devarbhavi, Harshad; Andrade, Raúl J

2014-05-01

Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

AtriplaR/anti-TB combination in TB/HIV patients. Drug in focus

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Semvua Hadija H

2011-11-01

Full Text Available Abstract Background Co-administration of anti-tuberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and several antiretroviral drugs is complicated by pharmacokinetic drug-drug interaction. Method Pubmed and Google search following the key words tuberculosis, HIV, emtricitabine, tenofovir efavirenz, interaction were used to find relevant information on each drug of the fixed dose combination AtriplaR Results Information on generic name, trade name, pharmacokinetic parameter, metabolism and the pharmacokinetic interaction with Anti-TB drugs of emtricitabine, tenofovir, and efavirenz was obtained. Conclusion Fixed dose combination of emtricitabine/tenofovir/efavirenz (ATRIPLAR which has been approved by Food and Drug Administration shows promising results as far as safety and efficacy is concerned in TB/HIV co-infection patients, hence can be considered effective and safe antiretroviral drug in TB/HIV management for adult and children above 3 years of age.

Parkinsonian syndroms: Clinical phenotype, differential diagnosis and disease progression

International Nuclear Information System (INIS)

Storch, A.

2002-01-01

Parkinsonian syndromes include idiopathic Parkinson's disease (IPD), other neurodegenerative diseases with parkinsonism, the so-called atypical parkinsonian syndromes, and symptomatic parkinsonian syndromes, such as Wilson's disease. IPD is the most frequent disease with parkinsonism as the main clinical feature and is responsible for approx. 80% of all parkinsonian syndromes. Atypical parkinsonian syndromes are the most important differential diagnoses of IPD. The two most frequent types are multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). For clinical diagnosis it is essential to take a careful medical history and to examine the patients physically in regular intervals. However, various clinico-pathological studies have shown that approx. 25% of patients with clinical diagnosis of IPD may have other causes of parkinsonism. Selected technical investigations, in particular functional imaging of the central dopaminergic system using PET or SPECT, may help to make clinical diagnosis more secure. This paper reviews the clinical features and diagnostic findings in diseases with parkinsonism and summarises the difficulties in establishing early and differential diagnoses. (orig.) [de

Therapeutic genes for anti-HIV/AIDS gene therapy.

Science.gov (United States)

Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

2013-01-01

The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety.

Science.gov (United States)

Roth, Sanford H

2011-01-01

Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.

Comparison of British Thoracic Society and American Thoracic Society reintroduction guidelines for anti-tuberculous therapy induced liver injury

International Nuclear Information System (INIS)

Zuberi, B. F.; Alvi, H.; Zuberi, F. F.; Salahuddin, J.

2014-01-01

Objective: To compare the efficacy of British Thoracic Society and American Thoracic Society guidelines for re-introduction of anti-tuberculous therapy after drug-induced liver injury, and to assess the ease of administration of each guideline on a scale of 1-10. Methods: The randomised prospective interventional study was conducted at the Department of Medicine and Pulmonology, Dow University of Health Sciences, Karachi, from December 2011 to November 2013. Patients with anti-tuberculous therapy drug-induced liver injury were selected. Hepatotoxic anti-tuberculous therapy was stopped and modified anti-tuberculous therapy was started. Patients were followed weekly till clinical and biochemical parameters got stabilised. After stabilisation, the patients were randomised to one of the two groups to receive re-introduction of anti-tuberculous therapy under the guidelines of British Thoracic Society (Group I) or those of American Thoracic Society (Group II). Means of the groups were analysed by Student's t test and proportions were compared by chi-square test. Multivariate analysis was done for age, body mass index and serum albumin for recurrence of drug-induced liver injury after the re-introduction. P value <0.05 was taken as significant. Results: Of the total 325 patients, 163(50.15%) were in Group I, while 162(49.84%) were in Group II. The frequency of recurrence of drug-induced liver injury in Group I was 16 (9.8%) and in Group II it was 18 (11.1%). There was no statistically significant difference between the two groups (p<0.7). Age was positively related with drug-induced liver injury, while body mass index and serum albumin were negatively associated. Conclusion: There was no significant difference between the two major guidelines though the American Thoracic Society guideline was easier to follow. (author)

Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs

International Nuclear Information System (INIS)

Huang, Hai; Zhou, Wei; Zhu, Haiyan; Zhou, Pei; Shi, Xunlong

2017-01-01

Background: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. Objectives: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance. Methods: The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism. Results and discussion: BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBV rtM204V/rtLl80M transfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1 kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs. - Highlights: • Baicalin benefits the anti-HBV therapy. • Baicalin enhances ETV antiviral efficacy and overcomes NA-resistant HBV mutation. • The anti-HBV effect of baicalin is achieved by inhibiting HBV RNAs. • Baicalin down-regulates HBV replication-dependent host factors HNF 1α and HNF 4α.

Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs

Energy Technology Data Exchange (ETDEWEB)

Huang, Hai, E-mail: HHai3552@sina.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Zhou, Wei, E-mail: zhouw@fudan.edu.cn [Department of Chemistry, Fudan University, 220 Han Dan Road, Shanghai 200433 (China); Zhu, Haiyan, E-mail: haiyanzhu@fudan.edu.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Zhou, Pei, E-mail: pzhou@shmu.edu.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Shi, Xunlong, E-mail: xunlongshi@fudan.edu.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China)

2017-05-15

Background: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. Objectives: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance. Methods: The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism. Results and discussion: BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBV{sup rtM204V/rtLl80M} transfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1 kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs. - Highlights: • Baicalin benefits the anti-HBV therapy. • Baicalin enhances ETV antiviral efficacy and overcomes NA-resistant HBV mutation. • The anti-HBV effect of baicalin is achieved by inhibiting HBV RNAs. • Baicalin down-regulates HBV replication-dependent host factors HNF 1α and HNF 4α.

Anti-inflammatory therapy for urinary tract infection in children

Directory of Open Access Journals (Sweden)

A. A. Vyalkova

2015-01-01

Full Text Available Objective: to substantiate the importance of an etiological approach to diagnosing urinary tract infection in children in terms of the species and biological properties of an infectious agent and to evaluate the efficiency of anti-inflammatory therapy. The study included 116 patients aged 3-15 years with chronic pyelonephritis (Group 1 and isolated bacteriuria (Group 2. After 10-14-day antibiotic therapy, Group 1 patients were allocated to two subgroups: Subgroup la («=30 took furamag 5 mg/kg/day; Subgroup lb («=30 received furamag at the same dose in combination with canephron. The treatment cycle lasted 10-14 days. Subgroup 2a («=26 children had furamag 5 mgДg/day and Subgroup 2b (« =30 took furamag in combination with canephron. The duration of treatment was 14 days. The investigators established the high efficiency of therapy with furamag for renal infection in the children with the active and decrement phases and that of the drug of choice for its monotherapy of isolated highly virulent bacteriuria. Therapeutic efficiency was proven to be related to the species and biological characteristics of an infectious agent. Anti-inflammatory therapy for pyelonephritis in terms of the species of pathogenic bacteria was ascertained to improve the efficiency of treatment. A rationale was provided for the individual choice of antibiotics, followed by the use of furamag, eubiotics, and drugs aimed at inhibiting virulence factors and persistence of the pathogen to sanitize the primary focus of infection.

Dynamical analysis of Parkinsonian state emulated by hybrid Izhikevich neuron models

Science.gov (United States)

Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Li, Huiyan; Loparo, Kenneth A.; Fietkiewicz, Chris

2015-11-01

Computational models play a significant role in exploring novel theories to complement the findings of physiological experiments. Various computational models have been developed to reveal the mechanisms underlying brain functions. Particularly, in the development of therapies to modulate behavioral and pathological abnormalities, computational models provide the basic foundations to exhibit transitions between physiological and pathological conditions. Considering the significant roles of the intrinsic properties of the globus pallidus and the coupling connections between neurons in determining the firing patterns and the dynamical activities of the basal ganglia neuronal network, we propose a hypothesis that pathological behaviors under the Parkinsonian state may originate from combined effects of intrinsic properties of globus pallidus neurons and synaptic conductances in the whole neuronal network. In order to establish a computational efficient network model, hybrid Izhikevich neuron model is used due to its capacity of capturing the dynamical characteristics of the biological neuronal activities. Detailed analysis of the individual Izhikevich neuron model can assist in understanding the roles of model parameters, which then facilitates the establishment of the basal ganglia-thalamic network model, and contributes to a further exploration of the underlying mechanisms of the Parkinsonian state. Simulation results show that the hybrid Izhikevich neuron model is capable of capturing many of the dynamical properties of the basal ganglia-thalamic neuronal network, such as variations of the firing rates and emergence of synchronous oscillations under the Parkinsonian condition, despite the simplicity of the two-dimensional neuronal model. It may suggest that the computational efficient hybrid Izhikevich neuron model can be used to explore basal ganglia normal and abnormal functions. Especially it provides an efficient way of emulating the large-scale neuron network

APPLICABILITY OF THE NON STEROID ANTIINFLAMMATORY DRUGS IN FEVER THERAPY OF CHILDREN

Directory of Open Access Journals (Sweden)

O.A. Mubarakshina

2008-01-01

Full Text Available The non steroid anti-inflammatory drugs are widely applied in the pediatric practices for the fever therapy among children. While choosing the medications from this group to prescribe them to the children, it is essential to get guided towards the highly efficient medications with the least risk of the side effects. Only Paracetamol and ibuprofen are fully compliant with this requirement. They are officially recommended by who as the anti febrile medications for use in pediatrics. In the given article, the author reviews the advantages of ibuprofen over to Paracetamol based on the data from the foreign randomized research. She pays certain attention to the safety issues during the ibuprofen based treatment and to the opportunities of the combined Paracetamol and ibuprofen based therapy.Key words: fever, treatment, non steroid anti-inflammatory drugs, children.

Spread of anti-malarial drug resistance: Mathematical model with implications for ACT drug policies

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Dondorp Arjen M

2008-11-01

Full Text Available Abstract Background Most malaria-endemic countries are implementing a change in anti-malarial drug policy to artemisinin-based combination therapy (ACT. The impact of different drug choices and implementation strategies is uncertain. Data from many epidemiological studies in different levels of malaria endemicity and in areas with the highest prevalence of drug resistance like borders of Thailand are certainly valuable. Formulating an appropriate dynamic data-driven model is a powerful predictive tool for exploring the impact of these strategies quantitatively. Methods A comprehensive model was constructed incorporating important epidemiological and biological factors of human, mosquito, parasite and treatment. The iterative process of developing the model, identifying data needed, and parameterization has been taken to strongly link the model to the empirical evidence. The model provides quantitative measures of outcomes, such as malaria prevalence/incidence and treatment failure, and illustrates the spread of resistance in low and high transmission settings. The model was used to evaluate different anti-malarial policy options focusing on ACT deployment. Results The model predicts robustly that in low transmission settings drug resistance spreads faster than in high transmission settings, and treatment failure is the main force driving the spread of drug resistance. In low transmission settings, ACT slows the spread of drug resistance to a partner drug, especially at high coverage rates. This effect decreases exponentially with increasing delay in deploying the ACT and decreasing rates of coverage. In the high transmission settings, however, drug resistance is driven by the proportion of the human population with a residual drug level, which gives resistant parasites some survival advantage. The spread of drug resistance could be slowed down by controlling presumptive drug use and avoiding the use of combination therapies containing drugs with

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

OpenAIRE

Roth, Sandford

2011-01-01

Sanford H RothArizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less...

Optimal Anti-cancer Drug Profiles for Effective Penetration of the Anti-cancer Drug Market by Generic Drugs in Japan.

Science.gov (United States)

Shibata, Shoyo; Matsushita, Maiko; Saito, Yoshimasa; Suzuki, Takeshi

2017-01-01

The increased use of generic drugs is a good indicator of the need to reduce the increasing costs of prescription drugs. Since there are more expensive drugs compared with other therapeutic areas, "oncology" is an important one for generic drugs. The primary objective of this article was to quantify the extent to which generic drugs in Japan occupy each level of the Anatomical Therapeutic Chemical (ATC) classification system. The dataset used in this study was created from publicly available information obtained from the IMS Japan Pharmaceutical Market database. Data on the total amount of sales and number of prescriptions for anti-cancer drugs between 2010 and 2016 in Japan were selected. The data were categorized according to the third level of the ATC classification system. All categories of the ATC classification system had increased market shares in Japan between 2010 and 2016. The barriers to market entry were relatively low in L01F (platinum anti-neoplastics), L01C (plant-based neoplastics), L02B (cytostatic hormone antagonists), and L01D (anti-neoplastic antibiotics) but were high in L02A (cytostatic hormones), L01H (protein kinase inhibitors), and L01B (anti-metabolites). Generic cancer drugs could bring savings to Japanese health care systems. Therefore, their development should be directed toward niche markets, such as L02A, L01H, and L01B, and not competitive markets.

Predictive value of dopamine transporter SPECT imaging with [123I]PE2I in patients with subtle parkinsonian symptoms

International Nuclear Information System (INIS)

Ziebell, Morten; Thomsen, Gerda; Knudsen, Gitte M.; Andersen, Birgitte B.; Pinborg, Lars H.; Karlsborg, Merete; Hasselbalch, Steen G.

2012-01-01

To examine the diagnostic sensitivity and specificity of dopamine transporter SPECT imaging with a highly dopamine transporter selective radioligand. The study included consecutively enrolled, drug-naive patients with an average short history of parkinsonian motor symptoms, referred for diagnostic scanning. The study group comprised 288 patients naive to antiparkinson treatment who were enrolled as they were admitted for a diagnostic SPECT scan with the radioligand [ 123 I]-N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl)n ortropane ( 123 I-PE2I). After the diagnostic scanning, patients were followed clinically with an average follow-up of 19.7 ± 12.5 months. A diagnosis could be clinically settled in 189 patients and among these patients, a dopamine transporter scan had a sensitivity of 88% and a specificity of 91% for discrimination between patients with and without striatal neurodegeneration. In cognitively impaired patients (Mini Mental State Examination 2 differentiated between idiopathic Parkinson's disease and atypical parkinsonian syndromes with a specificity of 84% and a sensitivity of 63%. In drug-naive patients with subtle clinical parkinsonian motor symptoms, dopamine transporter scan using 123 I-PE21 has a high sensitivity and specificity in distinguishing between patients with and without striatal neurodegeneration. The specificity is lower in patients who are also cognitively impaired. Calculation of the striatal APR can assist in differentiating between idiopathic Parkinson's disease and atypical parkinsonian syndromes. (orig.)

Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors

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Miyatake S

2016-08-01

Full Text Available Shouta Miyatake,1 Yuko Shimizu-Motohashi,2 Shin’ichi Takeda,1 Yoshitsugu Aoki1 1Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan; 2Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan Abstract: Duchenne muscular dystrophy (DMD, an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD. Keywords: calcium channels, ryanodine receptor 1, exon skipping, NF-κB, myokine, ROS

Does anti-malarial drug knowledge predict anti-malarial dispensing practice in drug outlets? A survey of medicine retailers in western Kenya

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Rusk Andria

2012-08-01

Full Text Available Abstract Background Malaria is a major cause of morbidity and mortality in Kenya, where it is the fifth leading cause of death in both children and adults. Effectively managing malaria is dependent upon appropriate treatment. In Kenya, between 17 to 83 percent of febrile individuals first seek treatment for febrile illness over the counter from medicine retailers. Understanding medicine retailer knowledge and behaviour in treating suspected malaria and dispensing anti-malarials is crucial. Methods To investigate medicine retailer knowledge about anti-malarials and their dispensing practices, a survey was conducted of all retail drug outlets that sell anti-malarial medications and serve residents of the Webuye Health and Demographic Surveillance Site in the Bungoma East District of western Kenya. Results Most of the medicine retailers surveyed (65% were able to identify artemether-lumefantrine (AL as the Kenyan Ministry of Health recommended first-line anti-malarial therapy for uncomplicated malaria. Retailers who correctly identified this treatment were also more likely to recommend AL to adult and paediatric customers. However, the proportion of medicine retailers who recommend the correct treatment is disappointingly low. Only 48% would recommend AL to adults, and 37% would recommend it to children. It was discovered that customer demand has an influence on retailer behaviour. Retailer training and education were found to be correlated with anti-malarial drug knowledge, which in turn is correlated with dispensing practices. Medicine retailer behaviour, including patient referral practice and dispensing practices, are also correlated with knowledge of the first-line anti-malarial medication. The Kenya Ministry of Health guidelines were found to influence retailer drug stocking and dispensing behaviours. Conclusion Most medicine retailers could identify the recommended first-line treatment for uncomplicated malaria, but the percentage that could

Smart Drug Delivery Systems in Cancer Therapy.

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Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Anti-VEGF drugs: evidence for effectiveness

OpenAIRE

Evans, Jennifer; Virgili, Gianni

2014-01-01

Anti-vascular endothelial growth factors (anti-VEGF) are targeted biological drugs (e.g. monoclonal antibodies) that prevent the growth of new vessels by inhibiting VEGF. VEGF is a cytokine (cell-signalling protein) that promotes the growth of, and leakage from, new vessels. Currently there are three anti-VEGF drugs licensed for use in eye disease: pegaptanib, aflibercept, ranibizumab and one that is not licensed but is commonly used off-label (bevacizumab).

Characterization of Nanodiamond-based anti-HIV drug Delivery to the Brain.

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Roy, Upal; Drozd, Vadym; Durygin, Andriy; Rodriguez, Jesse; Barber, Paul; Atluri, Venkata; Liu, Xiaohua; Voss, Thomas G; Saxena, Surendra; Nair, Madhavan

2018-01-25

Human Immunodeficiency Virus Type 1 (HIV-1) remains one of the leading causes of death worldwide. Present combination antiretroviral therapy has substantially improved HIV-1 related pathology. However, delivery of therapeutic agents to the HIV reservoir organ like Central nervous system (CNS) remains a major challenge primarily due to the ineffective transmigration of drugs through Blood Brain Barrier (BBB). The recent advent of nanomedicine-based drug delivery has stimulated the development of innovative systems for drug delivery. In this regard, particular focus has been given to nanodiamond due to its natural biocompatibility and non-toxic nature-making it a more efficient drug carrier than other carbon-based materials. Considering its potential and importance, we have characterized unmodified and surface-modified (-COOH and -NH 2 ) nanodiamond for its capacity to load the anti-HIV-1 drug efavirenz and cytotoxicity, in vitro. Overall, our study has established that unmodified nanodiamond conjugated drug formulation has significantly higher drug loading capacity than surface-modified nanodiamond with minimum toxicity. Further, this nanodrug formulation was characterized by its drug dissolution profile, transmigration through the BBB, and its therapeutic efficacy. The present biological characterizations provide a foundation for further study of in-vivo pharmacokinetics and pharmacodynamics of nanodiamond-based anti-HIV drugs.

Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

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John F. Flynn

2009-01-01

Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

Prescription Pattern Analysis of Nonsteroidal Anti-inflammatory Drugs in the Northeastern Iranian Population

NARCIS (Netherlands)

Zeinali, Majid; Tabeshpour, Jamshid; Maziar, Seyed Vahid; Taherzadeh, Zhila; Zirak, Mohammad Reza; Sent, Danielle; Azarkhiavi, Kamal Razavi; Eslami, Saeid

2017-01-01

Inappropriate nonsteroidal anti-inflammatory drugs (NSAIDs) therapy is a common cause of actual and potential adverse effects, such as bleeding and gastrointestinal ulceration, which exacerbates the patient's medical condition and might even be life threatening. We aimed to evaluate and analyze the

Cost-effectiveness of drug monitoring of anti-TNF therapy in inflammatory bowel disease and rheumatoid arthritis: a systematic review.

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Martelli, Laura; Olivera, Pablo; Roblin, Xavier; Attar, Alain; Peyrin-Biroulet, Laurent

2017-01-01

Therapeutic drug monitoring (TDM) of anti-TNF is increasingly used to manage inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA). The cost-effectiveness of this strategy is debated. All studies comparing the cost-effectiveness of a TDM-based strategy and an empirical dose management of anti-TNF in IBD or RA were screened. Studies were identified through the MEDLINE electronic database (up to July 2016), and annual international meeting abstracts were also manually reviewed. Seven studies were included: two randomized controlled trials (RCTs) enrolling 332 patients [247 Crohn's disease (CD) and 85 ulcerative colitis (UC)] and five modeling approaches. Four studies included only CD patients, one included both CD and UC patients, and two included only RA patients. Three studies compared the cost-effectiveness of the two strategies in patients with secondary infliximab (IFX) failure (dose-escalation strategy), one in patients in remission on optimized IFX (de-escalation strategy), one in patients starting adalimumab, and two in patients with clinical response to maintenance anti-TNF therapy. The two RCTs demonstrated that a TDM strategy led to major cost savings, ranging from 28 to 34 %. The three modeling approaches with regard to CD patients demonstrated cost savings ranging from $5396 over a 1-year period to €13,130 per patient at 5 years of follow-up. A TDM strategy also led to major cost savings in the two modeling approaches in RA patients. Available evidence indicates that a TDM strategy leads to major cost savings related to anti-TNF therapy in both IBD and RA patients, with no negative impact on efficacy.

Deep brain stimulation of the center median-parafascicular complex of the thalamus has efficient anti-parkinsonian action associated with widespread cellular responses in the basal ganglia network in a rat model of Parkinson's disease.

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Jouve, Loréline; Salin, Pascal; Melon, Christophe; Kerkerian-Le Goff, Lydia

2010-07-21

The thalamic centromedian-parafascicular (CM/Pf) complex, mainly represented by Pf in rodents, is proposed as an interesting target for the neurosurgical treatment of movement disorders, including Parkinson's disease. In this study, we examined the functional impact of subchronic high-frequency stimulation (HFS) of Pf in the 6-hydroxydopamine-lesioned hemiparkinsonian rat model. Pf-HFS had significant anti-akinetic action, evidenced by alleviation of limb use asymmetry (cylinder test). Whereas this anti-akinetic action was moderate, Pf-HFS totally reversed lateralized neglect (corridor task), suggesting potent action on sensorimotor integration. At the cellular level, Pf-HFS partially reversed the dopamine denervation-induced increase in striatal preproenkephalin A mRNA levels, a marker of the neurons of the indirect pathway, without interfering with the markers of the direct pathway (preprotachykinin and preprodynorphin). Pf-HFS totally reversed the lesion-induced changes in the gene expression of cytochrome oxidase subunit I in the subthalamic nucleus, the globus pallidus, and the substantia nigra pars reticulata, and partially in the entopeduncular nucleus. Unlike HFS of the subthalamic nucleus, Pf-HFS did not induce per se dyskinesias and directly, although partially, alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced forelimb dyskinesia. Conversely, L-DOPA treatment negatively interfered with the anti-parkinsonian effect of Pf-HFS. Altogether, these data show that Pf-DBS, by recruiting a large basal ganglia circuitry, provides moderate to strong anti-parkinsonian benefits that might, however, be affected by L-DOPA. The widespread behavioral and cellular outcomes of Pf-HFS evidenced here demonstrate that CM/Pf is an important node for modulating the pathophysiological functioning of basal ganglia and related disorders.

[Reversible infertility from nonsteroidal anti-inflammatory drugs].

Science.gov (United States)

Skomsvoll, Johan Fredrik; Rødevand, Erik; Koksvik, Hege Svean; Salvesen, Kjell Asmund; von Düring, Vidar; Rygnestad, Tarjei; Østensen, Monika

2005-06-02

Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors may interfere with ovulation and the rupture of the follicle, causing reversible infertility. Literature review. Reversible infertility is shown both in animal and human studies of these drugs. As determined by ultrasound, the drugs may delay or inhibit ovulation. These findings are also confirmed by a few randomized controlled studies showing an increase in time from the luteinizing hormone surge to rupture of the follicle and an increased size of the unruptured follicle. Most of the hormone analyses show values in accordance with the ovulation/menstrual cycle. Also, two epidemiological studies have shown an association between NSAID use and spontaneous abortion. These studies have methodological weaknesses and their findings have to be elucidated in future studies. Women with fertility problems should avoid not only the selective cyclooxygenase-2 inhibitors, but also the traditional NSAIDs. However, women with rheumatic disease responding well to therapy should consult their physicians before stopping treatment. Reduced dose of a NSAID and temporary stop of drug treatment early in the menstrual cycle, or alternative drug treatment, may be a solution. NSAIDs should not be used in the last eight weeks of pregnancy.

Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies? A systematic review.

Science.gov (United States)

Polak, David; Martin, Conchita; Sanz-Sánchez, Ignacio; Beyth, Nurit; Shapira, Lior

2015-04-01

Systematically review the scientific evidence for efficiency of anti-inflammatory agents against gingivitis, either as solo treatments or adjunctive therapies. A protocol was developed aimed to answer the following focused question: "Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies?" RCTs and cohort studies on anti-inflammatory agents against gingivitis studies were searched electronically. Screening, data extraction and quality assessment were conducted. The primary outcome measures were indices of gingival inflammation. A sub-analysis was performed dividing the active agents into anti-inflammatory and other drugs. The search identified 3188 studies, of which 14 RCTs met the inclusion criteria. The use of anti-inflammatory or other agents, in general showed a higher reduction in the test than in the control in terms of gingival indexes and bleeding scores. Only two RCTs on inflammatory drugs could be meta-analysed, showing a statistically significant reduction in the GI in the experimental group [WMD = -0.090; 95% CI (-0.105; -0.074); p = 0.000]. However, the contribution of both studies to the global result was unbalanced (% weight: 99.88 and 0.12 respectively). Most of the tested material showed beneficial effect as anti-inflammatory agents against gingivitis, either as a single treatment modality or as an adjunctive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Weight Gain and Hair Loss during Anti-TNF Therapy

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Abdo Lutf

2012-01-01

Full Text Available Objectives. To investigate the incidence of weight gain and hair loss as adverse effects of anti-TNF therapy in rheumatic diseases. Methods. Patients using anti-TNF therapy, who are followed in rheumatology clinic, were interviewed using a questionnaire to investigate the side effects of anti-TNF therapy. Patients who complained of hair loss and weight gain were asked additional questions concerning the relationship of these adverse effects to anti-TNF use, whether therapy was stopped because of these adverse effects and if the adverse effects reversed after stopping therapy. The files were reviewed to follow the weight change before, during, and after discontinuation of anti-TNF. Results. One hundred fifty consecutive patients (82 RA, 34 ankylosing spondylitis, 32 psoriatic arthritis, and 4 for other indications were interviewed .Weight gain was observed in 20 patients (13.3% with average gain of 5.5 Kg. Anti-TNF was stopped in five patients because of this adverse effect. Hair loss during anti-TNf therapy was reported in five females (3.3% and anti-TNF therapy was stopped in all of them. Conclusion. Weight gain and hair loss appear to be associated with anti-TNF therapy and may be one reason for discontinuing the therapy.

Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers.

Science.gov (United States)

Nair, Madhavan; Guduru, Rakesh; Liang, Ping; Hong, Jeongmin; Sagar, Vidya; Khizroev, Sakhrat

2013-01-01

Although highly active anti-retroviral therapy has resulted in remarkable decline in the morbidity and mortality in AIDS patients, inadequately low delivery of anti-retroviral drugs across the blood-brain barrier results in virus persistence. The capability of high-efficacy-targeted drug delivery and on-demand release remains a formidable task. Here we report an in vitro study to demonstrate the on-demand release of azidothymidine 5'-triphosphate, an anti-human immunodeficiency virus drug, from 30 nm CoFe2O4@BaTiO3 magneto-electric nanoparticles by applying a low alternating current magnetic field. Magneto-electric nanoparticles as field-controlled drug carriers offer a unique capability of field-triggered release after crossing the blood-brain barrier. Owing to the intrinsic magnetoelectricity, these nanoparticles can couple external magnetic fields with the electric forces in drug-carrier bonds to enable remotely controlled delivery without exploiting heat. Functional and structural integrity of the drug after the release was confirmed in in vitro experiments with human immunodeficiency virus-infected cells and through atomic force microscopy, spectrophotometry, Fourier transform infrared and mass spectrometry studies.

Development of a controlled-release anti-parkinsonian nanodelivery system using levodopa as the active agent

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Kura AU

2013-03-01

Full Text Available Aminu Umar Kura,1 Samer Hasan Hussein Al Ali,2 Mohd Zobir Hussein,3 Sharida Fakurazi,1,4 Palanisamy Arulselvan11Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology, 4Faculty of Medicine and Health Science, Pharmacology Unit, Universiti Putra Malaysia, Selangor, MalaysiaAbstract: A new layered organic–inorganic nanocomposite material with an anti-parkinsonian active compound, L-3-(3,4-dihydroxyphenyl alanine (levodopa, intercalated into the inorganic interlayers of a Zn/Al-layered double hydroxide (LDH was synthesized using a direct coprecipitation method. The resulting nanocomposite was composed of the organic moiety, levodopa, sandwiched between Zn/Al-LDH inorganic interlayers. The basal spacing of the resulting nanocomposite was 10.9 Å. The estimated loading of levodopa in the nanocomposite was approximately 16% (w/w. A Fourier transform infrared study showed that the absorption bands of the nanocomposite were characteristic of both levodopa and Zn/Al-LDH, which further confirmed intercalation, and that the intercalated organic moiety in the nanocomposite was more thermally stable than free levodopa. The resulting nanocomposite showed sustained-release properties, so can be used in a controlled-release formulation. Cytotoxicity analysis using an MTT assay also showed increased cell viability of 3T3 cells exposed to the newly synthesized nanocomposite compared with those exposed to pure levodopa after 72 hours of exposure.Keywords: levodopa, layered double hydroxides, coprecipitation, sustained release

Modulating basal ganglia and cerebellar activity to suppress parkinsonian tremor

NARCIS (Netherlands)

Heida, Tjitske; Zhao, Yan; van Wezel, Richard Jack Anton

2013-01-01

Despite extensive research, the detailed pathophysiology of the parkinsonian tremor is still unknown. It has been hypothesized that the generation of parkinsonian tremor is related to abnormal activity within the basal ganglia. The cerebello-thalamic-cortical loop has been suggested to indirectly

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

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Roth SH

2011-05-01

Full Text Available Sanford H RothArizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.Keywords: NSAIDs, osteoarthritis, topical administration, synovial fluid, peptic ulcer, Helicobacter pylori

Incidence, clinical features and impact on anti-tuberculosis treatment of anti-tuberculosis drug induced liver injury (ATLI in China.

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Penghui Shang

Full Text Available Anti-tuberculosis drug induced liver injury (ATLI is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB treatment in China.In a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%-3.06%. Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02% ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25% recovered, 18 (16.98% improved, 2 (1.89% failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89% died as result of ATLI. Of all the ATLI cases, 74 (69.81% cases changed their anti-TB treatment, including 4 (3.77% cases with medication administration change, 21 (19.81% cases with drugs replacement, 54 (50.94% cases with therapy interruption, and 12 (11.32% cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46% cases had TB cured in time, 48 (46.60% cases had therapy prolonged, and 2 (1.94% cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69-15.05 risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI, 1.23-3.60 risk of prolonged intensive treatment phase.ATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the prevention of ATLI.

Fibrocytes: A Novel Stromal Cells to Regulate Resistance to Anti-Angiogenic Therapy and Cancer Progression.

Science.gov (United States)

Goto, Hisatsugu; Nishioka, Yasuhiko

2017-12-29

An adequate blood supply is essential for cancer cells to survive and grow; thus, the concept of inhibiting tumor angiogenesis has been applied to cancer therapy, and several drugs are already in clinical use. It has been shown that treatment with those anti-angiogenic drugs improved the response rate and prolonged the survival of patients with various types of cancer; however, it is also true that the effect was mostly limited. Currently, the disappointing clinical results are explained by the existence of intrinsic or acquired resistance to the therapy mediated by both tumor cells and stromal cells. This article reviews the mechanisms of resistance mediated by stromal cells such as endothelial cells, pericytes, fibroblasts and myeloid cells, with an emphasis on fibrocytes, which were recently identified as the cell type responsible for regulating acquired resistance to anti-angiogenic therapy. In addition, the other emerging role of fibrocytes as mediator-producing cells in tumor progression is discussed.

Use of anti-obesity drugs among college students.

Science.gov (United States)

Martins, Maria do Carmo de Carvalho e; Souza Filho, Manoel Dias de; Moura, Felipe Scipião; Carvalho, Juliana de Sousa Ribeiro de; Müller, Marina Costa; Neves, Rebeka Valença; Mousinho, Patrícia Coelho; Lima, Iúri Paz

2011-01-01

To evaluate the use of anti-obesity drugs among students attending a public university. This was a cross sectional random study of 664 college students. Drug use, socioeconomic, and anthropometric variables were observed. Body mass index (BMI) and waist circumference (WC) were classified according to World Health Organization criteria. Current or previous use of anti-obesity drugs was reported by 6.8% of students. Amphetamine and sympathomimetic amines (40.5%) were the most commonly used drugs. Among those who reported use of anti-obesity agents, 62.2% were female. Only 31.1% of medications were prescribed by doctors. Mean BMI and WC were higher among students reporting the use of such drugs, but 47% of them were classified as eutrophic by BMI, and 76.5% had normal WC measure. The use of anti-obesity drugs among college students is of concern, particularly due to the high proportion of drug use without indication or prescription.

Monitoring early tumor response to drug therapy with diffuse optical tomography

Science.gov (United States)

Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

2012-01-01

Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

SEXUAL DYSFUNCTION INDUCED BY ANTI-PSYCHOTICS AND ANTI-DEPRESSANTS IN DRUG NAIVE PATIENTS – A COMPARATIVE STUDY

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M. Mohanalakshmi

2017-03-01

Full Text Available BACKGROUND The aim of this study was to determine and compare sexual dysfunction caused by anti-psychotics and anti-depressants in drug naïve patients. MATERIALS AND METHODS Patients diagnosed as drug naïve schizophrenic and depression as per DSM-5 criteria & age between 18-45 years were recruited and allocated into group A (n=30–receiving anti-psychotics & group B (n=30 receiving anti-depressants after informed consent by the patients. Sexual dysfunction was assessed by Arizona Sexual Experiences Scale (ASEX during the initial 2 months of therapy. RESULTS ASEX mean for patients receiving antipsychotics increased from the baseline of 7.97 to 17.23 and the ASEX mean for patients receiving antidepressants increased from baseline of 7.80 to 18.67 with p value of 0.249 which is not statistically significant. Among the antipsychotics haloperidol ASEX mean increased from 7.87 to 18.00 and risperidone mean increased from 8.07 to 16.47 with the p value of 0.335 which is not significant. More patients on haloperidol showed evidence of sexual dysfunction as assessed by ASEX scoring than risperidone though p value was not significant. Among the two antidepressants ASEX score mean for amitriptyline patients increased from 8.07 to 16.47, and that of fluoxetine from 7.53 to 16.47 with the p value of 0.018* statistically significant at α of 0.05 level. CONCLUSION This study shows presence of sexual dysfunction in patients receiving antipsychotics & antidepressants by 2 nd month of therapy though statistically not significant. Fluoxetine group patients developed statistically significant sexual dysfunction. Implications for future research about sexual dysfunction in all new treatments should be strongly taken into account because this side effect adds to the emotional stress and worsening of mental dysfunction.

Biological anti-TNF drugs

DEFF Research Database (Denmark)

Prado, Mônica Simon; Bendtzen, Klaus; Andrade, Luis Eduardo Coelho

2017-01-01

practice shows a significant percentage of individuals who do not exhibit the desired response. Loss of therapeutic benefit after initial successful response is designated secondary failure. Immune-biological agents are not self-antigens and are therefore potentially immunogenic. Secondary failure...... is frequently caused by antibodies against immune-biologicals, known as anti-drug antibodies (ADA). ADA that neutralize circulating immune-biologicals and/or promote their clearance can reduce treatment efficacy. Furthermore, ADA can induce adverse events by diverse immunological mechanisms. This review...... provides a comprehensive overview of ADA in rheumatoid arthritis patients treated with anti-TNF immune-biologicals, and explores the concept of therapeutic drug monitoring (TDM) as an effective strategy to improve therapeutic management. Expert opinion: Monitoring circulating ADA and therapeutic immune-biological...

Recovery of behavioral symptoms in hemi-parkinsonian rhesus monkeys through combined gene and stem cell therapy.

Science.gov (United States)

Zhou, Yan; Sun, Maosheng; Li, Hongjun; Yan, Min; He, Zhanlong; Wang, Wenju; Wang, Wanpu; Lu, Shuaiyao

2013-04-01

The use of adipose mesenchymal stromal cells (ASCs) in cellular and genic therapy has attracted considerable attention as a possible treatment for neurodegenerative disorders, including Parkinson disease. However, the effects of gene therapy combined with intracerebral cell transplantation have not been well defined. Recent studies have demonstrated the respective roles of LIM homeobox transcription factor 1, alpha (LMX1A) and Neurturin (NTN) in the commitment of embryonic stem cells (ESCs) to a midbrain dopaminergic neuronal fate and the commitment of mesenchymal stromal cells to cells supporting the nutrition and protection of neurons. We investigated a novel in vitro neuronal differentiation strategy with the use of LMX1A and Neurturin. We were able to elicit a neural phenotype regarding cell morphology, specific gene/protein expression and physiological function. Neuronal-primed ASCs derived from rhesus monkey (rASCs) combined with adenovirus containing NTN and tyrosine hydroxylase (TH) (Ad-NTN-TH) were implanted into the striatum and substantia nigra of methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned hemi-parkinsonian rhesus monkeys. Monkeys were monitored with the use of behavioral tests and health measures until the fourth month after implantation. The differentiated cells transcribed and expressed a variety of dopaminergic neuron-specific genes involved in the SHH/LMX1A pathway. Single-photon emission computed tomography analysis and postmortem analysis revealed that the grafting of rASCs combined with Ad-NTN-TH had neuroprotective effects compared with Ad-NTN-TH or rASCs alone. Behavioral measures demonstrated autograft survival and symptom amelioration. These findings may lead to cellular sources for autologous transplantation of Parkinson disease. Combined transplantation of Ad-NTN-TH and induced rASCs expressing LMX1A and NTN may be a better therapy candidate for the treatment of Parkinson disease. Copyright © 2013 International Society

Biodegradable polymers for targeted delivery of anti-cancer drugs.

Science.gov (United States)

Doppalapudi, Sindhu; Jain, Anjali; Domb, Abraham J; Khan, Wahid

2016-06-01

Biodegradable polymers have been used for more than three decades in cancer treatment and have received increased interest in recent years. A range of biodegradable polymeric drug delivery systems designed for localized and systemic administration of therapeutic agents as well as tumor-targeting macromolecules has entered into the clinical phase of development, indicating the significance of biodegradable polymers in cancer therapy. This review elaborates upon applications of biodegradable polymers in the delivery and targeting of anti-cancer agents. Design of various drug delivery systems based on biodegradable polymers has been described. Moreover, the indication of polymers in the targeted delivery of chemotherapeutic drugs via passive, active targeting, and localized drug delivery are also covered. Biodegradable polymer-based drug delivery systems have the potential to deliver the payload to the target and can enhance drug availability at desired sites. Systemic toxicity and serious side effects observed with conventional cancer therapeutics can be significantly reduced with targeted polymeric systems. Still, there are many challenges that need to be met with respect to the degradation kinetics of the system, diffusion of drug payload within solid tumors, targeting tumoral tissue and tumor heterogeneity.

The optimal management of anti-thrombotic therapy after valve replacement: certainties and uncertainties.

Science.gov (United States)

Iung, Bernard; Rodés-Cabau, Josep

2014-11-07

Anti-thrombotic therapy after valve replacement encompasses a number of different situations. Long-term anticoagulation of mechanical prostheses uses vitamin K antagonists with a target international normalized ratio adapted to the characteristics of the prosthesis and the patient. The association of low-dose aspirin is systematic in the American guidelines and more restrictive in the European guidelines. Early heparin therapy is frequently used early after mechanical valve replacement, although there are no precise recommendations regarding timing, type, and dose of drug. Direct oral anticoagulants are presently contraindicated in patients with mechanical prosthesis. The main advantage of bioprostheses is the absence of long-term anticoagulant therapy. Early anticoagulation is indicated after valve replacement for mitral bioprostheses, whereas aspirin is now favoured early after bioprosthetic valve replacement in the aortic position. Early dual antiplatelet therapy is indicated after transcatheter aortic valve implantation, followed by single antiplatelet therapy. However, this relies on low levels of evidence and optimization of anti-thrombotic therapy is warranted in these high-risk patients. Although guidelines are consistent in most instances, discrepancies and the low-level of evidence of certain recommendations highlight the need for further controlled trials, in particular with regard to the combination of antiplatelet therapy with oral anticoagulant and the early post-operative anti-thrombotic therapy following the procedure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Combined antiretroviral and anti- tuberculosis drug resistance ...

African Journals Online (AJOL)

these epidemics, many challenges remain.[3] Antiretroviral and anti-TB drug resistance pose considerable threats to the control of these epidemics.[4,5]. The breakdown in HIV/TB control within prisons is another emerging threat.[6,7] We describe one of the first reports of combined antiretroviral and anti-TB drug resistance ...

Thyroid hormone synthesis and anti-thyroid drugs

Indian Academy of Sciences (India)

The inhibition of thyroid hormone synthesis is required for the treatment of hyperthyroidism and this can be achieved by one or more anti-thyroid drugs. The most widely used anti-thyroid drug methimazole (MMI) inhibits the production of thyroid hormones by irreversibly inactivating the enzyme TPO. Our studies show that the ...

Role of antithyroid drug treatment prior to radioiodine therapy in hyperthyroidism

International Nuclear Information System (INIS)

Das, B.K.; Pradhan, P.K.; Senthilnathan, M.S.; Malhotra, G.

2005-01-01

Full text: Radio Iodine (RI) therapy is preceded by anti thyroid drug treatment in most centres. There is a general notion that this is a pre-requisite for RI therapy. There have been some sporadic reports in the past emphasizing that euthyroid state is not necessary in all cases before RI. However, no prospective randomized study has been reported in recent literature. The aim of this prospective study was to find out whether prior treatment with anti thyroid drugs showed any advantage in comparison to direct application of radio iodine in hyperthyroid patients. Seventy-two clinically and bio chemically proven cases of hyperthyroidism were randomized into two groups , each with 36 patients. They were matched by age, sex and size of goiter. After establishment of the diagnosis the patients were either subjected to anti thyroid drug treatment (Group A) or given calculated dose of radio iodine (Group B). After being euthyroid for at least 4 weeks the Group A patients were asked to stop the drugs (Neomercazole) for 3-5 days and radio iodine was administered. Patients in both groups were prescribed beta blockers for 4-6 weeks. Average radio iodine dose in both groups was 5 ± 0.92 mCi. All patients were evaluated both clinically and bio chemically 3, 6, 12 months after the radio iodine application. The duration to achieve euthyroid state, patient tolerance and side effects if any were meticulously recorded. In the pre treated group 72.1, 83.4 and 97.2% of the patients attained euthyroid state at 3, 6, 12 months respectively. Five patients needed a second dose after 3 months. No side effect or complications were observed. In group B 77.7, 88.8 and 94.4% of patients achieved euthyroid status at 3, 6 and 12 months respectively. There was no side effects or complications noted. However, 16.7 and 22.2% of the patients in group A and 27.7 and 36.1% of the group B became hypothyroid at 6 and 12 months respectively. They were treated with Thyroxine supplementation. Overall

Systemic Effects of Anti-Angiogenic Therapy

International Nuclear Information System (INIS)

Starlinger, P.

2011-01-01

Anti-angiogenic cancer therapy has gained importance within the past decades. In this context, Bevacizumab, a monoclonal antibody neutralizing vascular endothelial growth factor, has been approved for clinical use. The combination of chemotherapy with Bevacizumab has shown a remarkable benefit in several neoplastic entities. However, a notable number of patients do not respond to this therapy. Furthermore, response to therapy seems to be short-lived. The primary topic of this PhD thesis was to characterize systemic effects of anti-angiogenic therapy to possibly identify mechanisms that could explain this heterogeneity in therapy response. To this end, a carefully selected subset of angiogenesis factors were monitored in detail in the course of a clinical study of pancreatic cancer receiving gemcitabine based anti-angiogenic therapy with Bevacizumab. To enable the reliable monitoring of angiogenesis parameters, we initially defined an optimized procedure to evaluate angiogenesis factors in blood. During these investigations a remarkable association of circulating angiogenic growth factors with platelet counts and activation was observed. Strikingly, we were able to confirm this association in the clinical setting. In particular, the anti-angiogenic factor thrombospondin-1 (TSP-1) correlated with platelet counts. We further showed that the highly myelosuppressive chemotherapeutic agent gemcitabine resulted in a decrease of platelet counts and circulating TSP-1 levels. As a result, we hypothesized that the choice of chemotherapy might affect the angiogenic balance and counteract the therapeutic effect of bevacizumab. This notion was further supported by a careful evaluation of other studies reporting on the combination of Bevacizumab with thrombocytopenic chemotherapies which were generally of minor therapeutic benefit for cancer patients. To further focus on TSP-1 as an essential modulator of neovascularization and anti-angiogenic therapy we investigated TSP-1

A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole

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Ratih S. I. Putri

2016-11-01

Full Text Available The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC0-t, the area under the plasma concentration curve extrapolated to infinite time (AUC0-∞, the maximum plasma concentration (Cmax, the time to reach Cmax (tmax, and the plasma concentration half-life (t1/2. To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs for geometric mean ratios of both formulations were calculated for AUC and Cmax parameters, while tmax and t1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student’s paired t-test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%–101.34%, 95.53% (89.75%–101.68%, and 92.11% (84.35%–100.58% for AUC0-t, AUC0-∞, and Cmax, respectively. There were no statistically significant differences for tmax and t1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.

A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole.

Science.gov (United States)

Putri, Ratih S I; Setiawati, Effi; Aziswan, Syifa A; Ong, Fenny; Tjandrawinata, Raymond R; Susanto, Liana W

2016-11-18

The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS) detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC 0-t ), the area under the plasma concentration curve extrapolated to infinite time (AUC 0-∞ ), the maximum plasma concentration (C max ), the time to reach C max (t max ), and the plasma concentration half-life (t 1/2 ). To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs) for geometric mean ratios of both formulations were calculated for AUC and C max parameters, while t max and t 1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student's paired t -test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%-101.34%), 95.53% (89.75%-101.68%), and 92.11% (84.35%-100.58%) for AUC 0-t , AUC 0-∞ , and C max , respectively. There were no statistically significant differences for t max and t 1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.

Birth outcome in women with ulcerative colitis and Crohn's disease, and pharmacoepidemiological aspects of anti-inflammatory drug therapy.

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Nørgård, Bente Mertz

2011-12-01

The clinical epidemiological studies included in this thesis fall into three parts. The first part includes studies on birth outcome in women with ulcerative colitis. The second part includes pharmacoepidemiological studies on birth outcome after anti-inflammatory drug therapy in pregnancy, including patients with ulcerative colitis and Crohn's disease. The third part (and the latest publications) includes birth outcome in women with Crohn's disease; and the methods of cohort establishment in these studies are developed and improved due to the knowledge gathered from conducting the earlier studies. The birth outcomes in women with ulcerative colitis are examined in a nationwide, Danish, cohort of women based on data from the Danish National Hospital Discharge Registry and the Danish Medical Birth Registry, and within a Hungarian case-control data set. Our data suggest: 1) Significantly increased risk of preterm birth when women give birth 0-6 months after establishment of the diagnosis. It is considered whether the increased risk may be influenced by disease activity around the time of establishing the diagnosis. 2) No increased risk of giving birth to children with low birth weight, intrauterine growth retardation or congenital abnormalities (evaluated overall). 3) Significantly increased risk of some selected congenital abnormalities (limb deficiencies, obstructive urinary and multiple congenital abnormalities). No other studies have examined the risk of selected congenital abnormalities in children born by women with ulcerative colitis. The pharmacoepidemiological studies on birth outcomes after use of anti-inflammatory drug therapy in pregnancy, including women with ulcerative colitis and Crohn's disease, are based on data from the Hungarian case-control data set, a countywide Danish prescription Database, the Danish National Hospital Discharge Registry, the Danish Medical Birth Registry, and review of selected medical records. After exposure to sulfasalazine

Decreasing trends in hospitalizations during anti-TNF therapy are associated with time to anti-TNF therapy: Results from two referral centres.

Science.gov (United States)

Mandel, Michael D; Balint, Anita; Golovics, Petra A; Vegh, Zsuzsanna; Mohas, Anna; Szilagyi, Blanka; Szabo, Agnes; Kurti, Zsuzsanna; Kiss, Lajos S; Lovasz, Barbara D; Gecse, Krisztina B; Farkas, Klaudia; Molnar, Tamas; Lakatos, Peter L

2014-11-01

Hospitalization is an important outcome measure and a major driver of costs in patients with inflammatory bowel disease. We analysed medical and surgical hospitalization rates and predictors of hospitalization before and during anti-TNF therapy. Data from 194 consecutive patients were analysed retrospectively (males, 45.4%, median age at diagnosis, 24.0 years, infliximab/adalimumab: 144/50) in whom anti-TNF therapy was started after January 1, 2008. Total follow-up was 1874 patient-years and 474 patient-years with anti-TNF exposure. Hospitalization rates hospitalization decreased only in Crohn's disease (odds ratio: 0.59, 95% confidence interval: 0.51-0.70, median 2-years' anti-TNF exposure) with a same trend for surgical interventions (p=0.07), but not in ulcerative colitis. Need for hospitalization decreased in Crohn's disease with early (within 3-years from diagnosis, p=0.016 by McNemar test), but not late anti-TNF exposure. At logistic regression analysis complicated disease behaviour (p=0.03), concomitant azathioprine (p=0.02) use, but not anti-TNF type, gender, perianal disease or previous surgeries were associated with the risk of hospitalization during anti-TNF therapy. Hospitalization rate decreased significantly in patients with Crohn's disease but not ulcerative colitis after the introduction of anti-TNF therapy and was associated with time to therapy. Complicated disease phenotype and concomitant azathioprine use were additional factors defining the risk of hospitalization. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease?

Science.gov (United States)

Ward, Mark G; Irving, Peter M; Sparrow, Miles P

2015-10-28

In the last 15 years the management of inflammatory bowel disease has evolved greatly, largely through the increased use of immunomodulators and, especially, anti-tumor necrosis factor (anti-TNF) biologic agents. Within this time period, confidence in the use of anti-TNFs has increased, whilst, especially in recent years, the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines, combination therapy with an immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease, especially those who are recently diagnosed. Concurrently, therapeutic drug monitoring has emerged as a means of optimizing the dosage of both immunomodulators and anti-TNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent, or studies underpowered to analyze outcomes in combination therapy patients. It has been assumed that these target levels are applicable to patients on combination therapy also, however there are few data to support this. Similarly, the timing and duration of treatment with immunomodulators when used in combination therapy remains unknown. Recent attention, including post hoc analyses of the pivotal registration trials, has focused on the optimization of anti-TNF agents, when used as either monotherapy or combination therapy. This review will instead focus on how best to optimize immunomodulators when used in combination therapy, including an evaluation of recent data addressing unanswered questions regarding the optimal timing, dosage and duration of immunomodulator therapy in combination therapy patients.

Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib

DEFF Research Database (Denmark)

Macdonald, Thomas M; Hawkey, Chris J; Ford, Ian

2017-01-01

BACKGROUND: Selective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting...

Anti-Inflammatory Dimethylfumarate: A Potential New Therapy for Asthma?

Directory of Open Access Journals (Sweden)

Petra Seidel

2013-01-01

Full Text Available Asthma is a chronic inflammatory disease of the airways, which results from the deregulated interaction of inflammatory cells and tissue forming cells. Beside the derangement of the epithelial cell layer, the most prominent tissue pathology of the asthmatic lung is the hypertrophy and hyperplasia of the airway smooth muscle cell (ASMC bundles, which actively contributes to airway inflammation and remodeling. ASMCs of asthma patients secrete proinflammatory chemokines CXCL10, CCL11, and RANTES which attract immune cells into the airways and may thereby initiate inflammation. None of the available asthma drugs cures the disease—only symptoms are controlled. Dimethylfumarate (DMF is used as an anti-inflammatory drug in psoriasis and showed promising results in phase III clinical studies in multiple sclerosis patients. In regard to asthma therapy, DMF has been anecdotally reported to reduce asthma symptoms in patients with psoriasis and asthma. Here we discuss the potential use of DMF as a novel therapy in asthma on the basis of in vitro studies of its inhibitory effect on ASMC proliferation and cytokine secretion in ASMCs.

Effect of anti-obesity drug on cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials.

Directory of Open Access Journals (Sweden)

Yu-Hao Zhou

Full Text Available BACKGROUND: Anti-obesity drugs are widely used to prevent the complications of obesity, however, the effects of anti-obesity drugs on cardiovascular risk factors are unclear at the present time. We carried out a comprehensively systematic review and meta-analysis to assess the effects of anti-obesity drugs on cardiovascular risk factors. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles and proceedings of major meetings for relevant literatures. We included randomized placebo-controlled trials that reported the effects of anti-obesity drugs on cardiovascular risk factors compared to placebo. Overall, orlistat produced a reduction of 2.39 kg (95%CI-3.34 to -1.45 for weight, a reduction of 0.27 mmol/L (95%CI: -0.36 to -0.17 for total cholesterol, a reduction of 0.21 mmol/L (95%CI: -0.30 to -0.12 for LDL, a reduction of 0.12 mmol/L (95%CI: -0.20 to -0.04 for fasting glucose, 1.85 mmHg reduction (95%CI: -3.30 to -0.40 for SBP, and a reduction of 1.49 mmHg (95%CI: -2.39 to -0.58 for DBP. Sibutramine only showed effects on weight loss and triglycerides reduction with statistical significances. Rimonabant was associated with statistically significant effects on weight loss, SBP reduction and DBP reduction. No other significantly different effects were identified between anti-obesity therapy and placebo. CONCLUSION/SIGNIFICANCE: We identified that anti-obesity therapy was associated with a decrease of weight regardless of the type of the drug. Orlistat and rimonabant could lead to an improvement on cardiovascular risk factors. However, Sibutramine may have a direct effect on cardiovascular risk factors.

Bio markers and Anti-EGFR therapies for Krads wild-type tumors in metastatic colorectal cancer patients

International Nuclear Information System (INIS)

Diaz Rubio Garcia, E.

2009-01-01

The natural history of metastasis colorectal cancer has being clearly modified in terms of response rate, time to progression and overall survival, once the antiEGFR monoclonal antibodies (cetuximab and panitumumab) have emerged in combination with the standard cytotoxic chemotherapy (FOLFOX and FOLFIRI). However, the benefit from cetuximab and panitumumab is only confined to KRAS-wild type (KRAS-wt) colorectal tumors, while KRAS mutated tumors do not respond to these drugs. The 65 % of colorectal tumors are KRAS-wt tumors, but efficacy of antiEGFR therapies is detected only in 60-70 % of these KRAS-wt tumors. Other biomarkers and molecular pathways must be involved in the response of the antiEGFR therapies for the KRAS-wt colorectal tumors, such as the EGFR ligands, the EGFR-phosphorilated levels, the number of EGFR copies, the status of the KRAS effected B-RAF and the alternative intracellular signaling pathways PIK3CA/PTEN/AKT and JAK/STAT. A battery of these biomarkers is needed to select the most sensitive patients to the antiEGFR therapies. This pattern may represent a novel favorable cost-effectiveness tool to develop tailored treatments. A review of these biomarkers and molecular pathways, involved in the antiEGFR therapies response, is performed. (Author) 68 refs.

Differential Diagnosis of Patients with Inconclusive Parkinsonian Features Using [{sup 18}F]FP-CIT PET/CT

Energy Technology Data Exchange (ETDEWEB)

Park, Eunkyung; Hwang, Yu Mi; Lee, Channyoung; Oh, Sun Young; Kim, Young Chul; Choe, Jae Gol; Park, Kun Woo [Korea Univ., Seoul (Korea, Republic of); Kim, Sujin [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

2014-06-15

It is often difficult to differentiate parkinsonism, especially when patients show uncertain parkinsonian features. We investigated the usefulness of dopamine transporter (DAT) imaging for the differential diagnosis of inconclusive parkinsonism using [{sup 18}F]FP-CIT PET. Twenty-four patients with inconclusive parkinsonian features at initial clinical evaluation and nine healthy controls were studied. Patients consisted of three subgroups: nine patients whose diagnoses were unclear concerning whether they had idiopathic Parkinson's disease or drug-induced parkinsonism ('PD/DIP'), nine patients who fulfilled neither the diagnostic criteria of PD nor of essential tremor ('PD/ET'), and six patients who were alleged to have either PD or atypical parkinsonian syndrome ('PD/APS'). Brain PET images were obtained 120 min after injection of 185 MBq [{sup 18}F]FP-CIT. Imaging results were quantified and compared with follow-up clinical diagnoses. Overall, 11 of 24 patients demonstrated abnormally decreased DAT availability on the PET scans, whereas 13 were normal. PET results could diagnose PD/DIP and PD/ET patients as having PD in six patients, DIP in seven, and ET in five; however, the diagnoses of all six PD/APS patients remained inconclusive. Among 15 patients who obtained a final follow-up diagnosis, the image-based diagnosis was congruent with the follow-up diagnosis in 11 patients. Four unsolved cases had normal DAT availability, but clinically progressed to PD during the follow-up period. [{sup 18}F]FP-CIT PET imaging is useful in the differential diagnosis of patients with inconclusive parkinsonian features, except in patients who show atypical features or who eventually progress to PD.

Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug.

Science.gov (United States)

Dang, Tram T; Thai, Anh V; Cohen, Joshua; Slosberg, Jeremy E; Siniakowicz, Karolina; Doloff, Joshua C; Ma, Minglin; Hollister-Lock, Jennifer; Tang, Katherine M; Gu, Zhen; Cheng, Hao; Weir, Gordon C; Langer, Robert; Anderson, Daniel G

2013-07-01

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology toward a long-term cure for type I diabetes. Published by Elsevier Ltd.

Drug therapy problems identification by clinical pharmacists in a private hospital in Kuwait.

Science.gov (United States)

Bayoud, T; Waheedi, M; Lemay, J; Awad, A

2018-05-01

To report the types and frequency of drug therapy problems (DTPs) identified and the physician acceptance of the clinical pharmacist interventions in a private hospital in Kuwait. A retrospective cross-sectional study was conducted on 3500 patients admitted to the hospital between December 2010 and April 2013. A structured approach was used to identify DTPs and recommend interventions. Data were analyzed using MAXQDA version 11. A total of 670 DTPs were identified and recommendations were proposed to treating physicians for each DTP. Overdosage was the most frequently identified drug therapy problem (30.8%), followed by low dosage (17.6%), unnecessary drug therapy (17.3%), need for additional drug therapy (11.6%), and need for different drug product (11.6%). The drug classes most frequently involved were anti-infectives (36.9%), analgesics (25.2%), and gastrointestinal agents (15.5%). More than two-third of the interventions (67.5%) were accepted and implemented by physicians. The most frequently accepted interventions were related to nonadherence, adverse drug reaction, monitoring parameters, inappropriate dosage, and need for additional drug therapy. The current findings expand the existing body of data by reporting on pharmacist recommendations of identified DTPs and importantly, their high rate of acceptance and implementation by the treating physician. These results could serve as a springboard to support further development and implementation of clinical pharmacy services in other healthcare settings in Kuwait. Copyright © 2018 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Differential Diagnosis Tool for Parkinsonian Syndrome Using Multiple Structural Brain Measures

Directory of Open Access Journals (Sweden)

Miho Ota

2013-01-01

Full Text Available Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P and cerebellar subtype (MSA-C from Parkinson's disease is difficult in the early stage of the disease. To identify the correlative pattern of brain changes for differentiating parkinsonian syndromes, we applied discriminant analysis techniques by magnetic resonance imaging (MRI. T1-weighted volume data and diffusion tensor images were obtained by MRI in eighteen patients with MSA-C, 12 patients with MSA-P, 21 patients with Parkinson’s disease, and 21 healthy controls. They were evaluated using voxel-based morphometry and tract-based spatial statistics, respectively. Discriminant functions derived by step wise methods resulted in correct classification rates of 0.89. When differentiating these diseases with the use of three independent variables together, the correct classification rate was the same as that obtained with step wise methods. These findings support the view that each parkinsonian syndrome has structural deviations in multiple brain areas and that a combination of structural brain measures can help to distinguish parkinsonian syndromes.

Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs.

Science.gov (United States)

Huang, Hai; Zhou, Wei; Zhu, Haiyan; Zhou, Pei; Shi, Xunlong

2017-05-15

Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance. The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism. BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBV rtM204V/rtLl80M transfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs. Copyright © 2017 Elsevier Inc. All rights reserved.

Imidazoles and benzimidazoles as tubulin-modulators for anti-cancer therapy.

Science.gov (United States)

Torres, Fernando C; García-Rubiño, M Eugenia; Lozano-López, César; Kawano, Daniel F; Eifler-Lima, Vera L; von Poser, Gilsane L; Campos, Joaquín M

2015-01-01

Imidazoles and benzimidazoles are privileged heterocyclic bioactive compounds used with success in the clinical practice of innumerous diseases. Although there are many advancements in cancer therapy, microtubules remain as one of the few macromolecular targets validated for planning active anti-cancer compounds, and the design of drugs that modulate microtubule dynamics in unknown sites of tubulin is one of the goals of the medicinal chemistry. The discussion of the role of new and commercially available imidazole and benzimidazole derivatives as tubulin modulators is scattered throughout scientific literature, and indicates that these compounds have a tubulin modulation mechanism different from that of tubulin modulators clinically available, such as paclitaxel, docetaxel, vincristine and vinblastine. In fact, recent literature indicates that these derivatives inhibit microtubule formation binding to the colchicine site, present good pharmacokinetic properties and are capable of overcoming multidrug resistance in many cell lines. The understanding of the mechanisms involved in the imidazoles/benzimidazoles modulation of microtubule dynamics is very important to develop new strategies to overcome the resistance to anti-cancer drugs and to discover new biomarkers and targets for cancer chemotherapy.

Successful drug desensitization in patients with delayed-type allergic reactions to anti-tuberculosis drugs

Directory of Open Access Journals (Sweden)

Krittaecho Siripassorn

2018-03-01

Full Text Available Objective: To evaluate the outcomes of anti-tuberculosis drug desensitization. Methods: This was a retrospective study. Inclusion criteria were as follows: age >18 years, documented tuberculosis infection, a previous cutaneous allergic reaction to anti-tuberculosis drugs, and having undergone drug desensitization between January 2003 and March 2014. The definition of allergic reaction to anti-tuberculosis drugs included (1 a temporal relationship between drug use and the allergic reaction; (2 improvement in the allergic reaction after drug withdrawal; (3 recurrence of the allergic reaction after reintroduction of only the offending drug; and (4 absence of other causes. Results: A total of 19 desensitization procedures were performed. The drugs used for these procedures were isoniazid (n = 7, rifampicin (n = 6, or ethambutol (n = 6. Of note, severe allergic reactions (Stevens–Johnson syndrome (n = 4, erythema multiforme (n = 3, and drug rash with eosinophilia and systemic syndrome (n = 1 were included. All patients underwent resolution of the previous allergic reactions before desensitization. The median duration of desensitization was 18 days. The success rate was 78.9%. The allergic reactions following failed desensitization were not severe; most were maculopapular rashes. Conclusions: The desensitization protocol for anti-tuberculosis drugs was associated with a high success rate, and the individuals who failed desensitization experienced mild allergic reactions. Keywords: Desensitization, Antituberculosis, Steven-Johnson syndrome, Allergic drug reaction, Tolerance induction, Drug allergy

Anti-inflammatory drugs in the 21st century.

Science.gov (United States)

Rainsford, K D

2007-01-01

physiological processes whose inhibition was considered a major factor in development of adverse reactions, including those in the GI tract. At the turn of this century, there was enormous commercial development following the introduction of two new highly selective COX-2 inhibitors, known as coxibs (celecoxib and rofecoxib) which were claimed to have low GI side effects. While found to have fulfilled these aims in part, an alarming turn of events took place in the late 2004 period when rofecoxib was withdrawn worldwide because of serious cardiovascular events and other coxibs were subsequently suspected to have this adverse reaction, although to a varying degree. Major efforts are currently underway to discover why cardiovascular reactions took place with coxibs, identify safer coxibs, as well as elucidate the roles of COX-2 and COX-1 in cardiovascular diseases and stroke in the hope that there may be some basis for developing newer agents (e.g. nitric oxide-donating NSAIDs) to control these conditions. The discovery of the COX isoforms led to establishing their importance in many non-arthritic or non-pain states where there is an inflammatory component to pathogenesis, including cancer, Alzheimer's and other neurodegenerative diseases. The applications of NSAIDs and the coxibs in the prevention and treatment of these conditions as well as aspirin and other analogues in the prevention of thrombo-embolic diseases now constitute one of the major therapeutic developments of the this century. Moreover, new anti-inflammatory drugs are being discovered and developed based on their effects on signal transduction and as anti-cytokine agents and these drugs are now being heralded as the new therapies to control those diseases where cytokines and other nonprostaglandin components of chronic inflammatory and neurodegenerative diseases are manifest. To a lesser extent safer application of corticosteroids and the applications of novel drug delivery systems for use with these drugs as well

Pharmacokinetics of Anti-Epileptic Drugs and their Clinical Significance

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Svein I. Johannessen

1990-01-01

Full Text Available The serum concentration achieved and maintained following the administration of a fixed drug dosage is a direct consequence of the interactions of a wide variety of interrelated processes, including drug absorption, distribution, metabolism, and excretion, and the physiological status of the patient. These interrelationships are reviewed with specific reference to the major anti-epileptic drugs, phenobarbitone, phenytoin, sodium valproate, and carbamazepine, as well as a new first-line antiepileptic, oxcarbazepine. Both older drugs, such as phenobarbitone and phenytoin, and newer drugs, such as carbamazepine (CBZ and sodium valproate, have been studied extensively over the past years giving valuable information for drug treatment. An important feature of oxcarbazepine (OXC , which was developed through minimal changes in the structure of CBZ in order to improve on the tolerability of CBZ without sacrificing efficacy, is that its metabolites do not include the 11-epoxide which has been implicated in the side-effects of CBZ. In man, OXC is metabolized to a monohydroxy derivative which has independent anti-epileptic properties. OXC seems to lack several disadavantageous pharmacokinetic properties common to other major anti-epileptic drugs. OXC does not influence its own metabolism after repeated administration, in contrast to the auto-induction displayed by CBZ. The metabolism of OXC is not influenced by anti-epileptic co-medication and does not influence the kinetics of other anti-epileptic drugs – or if it does, then to a lesser extent than CBZ.

Adjunct therapy of Ayurvedic medicine with anti tubercular drugs on the therapeutic management of pulmonary tuberculosis.

Science.gov (United States)

Debnath, P K; Chattopadhyay, Jaydeb; Mitra, Achintya; Adhikari, Anjan; Alam, Mirza Samsur; Bandopadhyay, S K; Hazra, Jayram

2012-07-01

Pulmonary tuberculosis (PTB) is an age old disease described in Vedic Medicine as 'Yakshma'. Later on, in Ayurveda it earned a prefix and found way into mythology as 'Rajayakshma'. After the discovery of streptomycin, the therapeutic management of PTB received a major breakthrough. The treatment module changed remarkably with the formulation of newer anti-tubercular drugs (ATD) with appreciable success. Recent resurgence of PTB in developed countries like United States posed a threat to the medical community due to resistant strains. Consequently, WHO looked toward traditional medicine. Literature reveals that Ayurvedic treatment of PTB was in vogue in India before the introduction of ATD with limited success. Records show that 2766 patients of PTB were treated with Ayurvedic drugs in a tertiary care hospital in Kolkata in the year 1933-1947. To evaluate the toxicity reduction and early restoration by adjunct therapy of Ayurvedic drugs by increasing the bio-availability of ATDs. In the present study, treatment response of 99 patients treated with ATD as an adjunct with Aswagandha (Withania somnifera) and a multi-herbal formulation described in Chikitsa-sthana of Charaka samhita i.e. Chyawanprash were investigated. Hematological profile, sputum bacterial load count, immunoglobulin IgA and IgM, blood sugar, liver function test, serum creatinine were the assessed parameters besides blood isoniazid and pyrazinamide, repeated after 28 days of treatment. The symptoms abated, body weight showed improvement, ESR values were normal, there was appreciable change in IgA and IgM patterns and significantly increased bioavailability of isoniazid and pyrazinamide were recorded. This innovative clinical study coupled with empowered research may turn out to be promising in finding a solution for the treatment of PTB.

Methodologies Related to Computational models in View of Developing Anti-Alzheimer Drugs: An Overview.

Science.gov (United States)

Baheti, Kirtee; Kale, Mayura Ajay

2018-04-17

Since last two decades, there has been more focus on the development strategies related to Anti-Alzheimer's drug research. This may be attributed to the fact that most of the Alzheimer's cases are still mostly unknown except for a few cases, where genetic differences have been identified. With the progress of the disease, the symptoms involve intellectual deterioration, memory impairment, abnormal personality and behavioural patterns, confusion, aggression, mood swings, irritability Current therapies available for this disease give only symptomatic relief and do not focus on manipulations of biololecular processes. Nearly all the therapies to treat Alzheimer's disease, target to change the amyloid cascade which is considered to be an important in AD pathogenesis. New drug regimens are not able to keep pace with the ever-increasing understanding about dementia at molecular level. Looking into these aggravated problems, we though to put forth molecular modeling as a drug discovery approach for developing novel drugs to treat Alzheimer disease. The disease is incurable and it gets worst as it advances and finally causes death. Due to this, the design of drugs to treat this disease has become an utmost priority for research. One of the most important emerging technologies applied for this has been Computer-assisted drug design (CADD). It is a research tool that employs large scale computing strategies in an attempt to develop a model receptor site which can be used for designing of an anti-Alzheimer drug. The various models of amyloid-based calcium channels have been computationally optimized. Docking and De novo evolution are used to design the compounds. These are further subjected to absorption, distribution, metabolism, excretion and toxicity (ADMET) studies to finally bring about active compounds that are able to cross BBB. Many novel compounds have been designed which might be promising ones for the treatment of AD. The present review describes the research

Assessing bradykinesia in Parkinsonian disorders

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Gian ePal

2013-06-01

Full Text Available Objective: Bradykinesia is one of the clinical hallmarks of Parkinson’s disease (PD and atypical Parkinsonian syndromes. Clinical ratings scales and technology based assessments have been developed to measure bradykinesia. We review the different tools that exist for measurement of bradykinesia and analyze their reliability and applicability to PD and atypical Parkinsonian syndromes.Methods: We summarize data on the factor structure of the two primary scales used to assess PD, the Unified Parkinson’s Disease Rating Scale (UPDRS and Movement Disorder Society revision of the UPDRS, the MDS-UPDRS. We review how these scales have been used in atypical Parkinsonian syndromes, specifically Progressive Supranuclear Palsy (PSP. Finally, we report on the different technology based tools being used to assess bradykinesia. Results: The UPDRS is a useful measure of PD function and disability with 6 clinically distinct factors, 3 of which pertain to bradykinesia. The MDS-UPDRS has shown high internal consistency and correlation with the original UPDRS. Factor analysis of the UPDRS in PSP reveals 5 clinically distinct factors, 2 of which are independent bradykinesia factors. Thus the UPDRS and MDS-UPDRS are reliable and applicable scales for PD and the UPDRS can be used to assess bradykinesia in PSP. Technology based tools for measuring bradykinesia include gyrosensors, Coordination Ability Test System, Brain Test, quantitative digitography, Motus motion analysis system, PRIMAS, and the At-Home Testing Device. These tools have been compared to the UPDRS motor subscale and are effective in assessing bradykinesia.Conclusion: The UPDRS and MDS-UPDRS are well-established measures of bradykinesia that are applicable and useful in PD. The UPDRS is also been shown to be applicable to PSP. Different technologies exist to measure bradykinesia, though further work is needed to validate these assessment tools and bring them to clinical practice.

Mechanisms of termination and prevention of atrial fibrillation by drug therapy

Science.gov (United States)

Workman, AJ; Smith, GL; Rankin, AC

2011-01-01

Atrial fibrillation (AF) is a disorder of the rhythm of electrical activation of the cardiac atria. It is the most common cardiac arrhythmia, has multiple aetiologies, and increases the risk of death from stroke. Pharmacological therapy is the mainstay of treatment for AF, but currently available anti-arrhythmic drugs have limited efficacy and safety. An improved understanding of how anti-arrhythmic drugs affect the electrophysiological mechanisms of AF initiation and maintenance, in the setting of the different cardiac diseases that predispose to AF, is therefore required. A variety of animal models of AF has been developed, to represent and control the pathophysiological causes and risk factors of AF, and to permit the measurement of detailed and invasive parameters relating to the associated electrophysiological mechanisms of AF. The purpose of this review is to examine, consolidate and compare available relevant data on in-vivo electrophysiological mechanisms of AF suppression by currently approved and investigational anti-arrhythmic drugs in such models. These include the Vaughan Williams class I-IV drugs, namely Na+ channel blockers, β-adrenoceptor antagonists, action potential prolonging drugs, and Ca2+ channel blockers; the “upstream therapies”, e.g., angiotensin converting enzyme inhibitors, statins and fish oils; and a variety of investigational drugs such as “atrial-selective” multiple ion channel blockers, gap junction-enhancers, and intracellular Ca2+-handling modulators. It is hoped that this will help to clarify the main electrophysiological mechanisms of action of different and related drug types in different disease settings, and the likely clinical significance and potential future exploitation of such mechanisms. PMID:21334377

Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

Science.gov (United States)

Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

2018-01-01

The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

Combinational Therapy Enhances the Effects of Anti-IGF-1R mAb Figitumumab to Target Small Cell Lung Cancer.

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Hongxin Cao

Full Text Available Small cell lung cancer (SCLC is a recalcitrant malignancy with distinct biologic properties. Antibody targeting therapy has been actively investigated as a new drug modality.We tested the expression of IGF-1R and calculated the survival in 61 SCLC patients. We also evaluated the anti-tumor effects of anti-IGF-1R monoclonal antibody Figitumumab (CP on SCLC, and tried two drug combinations to improve CP therapy.Our clinical data suggested that high IGF-1R expression was correlated with low SCLC patient survival. We then demonstrated the effect of CP was likely through IGF-1R blockage and down-regulation without IGF-1R auto-phosphorylation and PI3K/AKT activation. However, we observed elevated MEK/ERK activation upon CP treatment in SCLC cells, and this MEK/ERK activation was enhanced by ß-arrestin1 knockdown while attenuated by ß-arrestin2 knockdown. We found both MEK/ERK inhibitor and metformin could enhance CP treatment in SCLC cells. We further illustrated the additive effect of metformin was likely through promoting further IGF-1R down-regulation.Our results highlighted the potential of anti-IGF-1R therapy and the adjuvant therapy strategy with either MEK/ERK inhibitor or metformin to target SCLC, warranting further studies.

Bi-Functionalized Clay Nanotubes for Anti-Cancer Therapy

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William R. Grimes

2018-02-01

Full Text Available Systemic toxicity is an undesired consequence of the majority of chemotherapeutic drugs. Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise towards personalized nanomedicine. Halloysite clay nanotubes (HNTs have shown potential as a drug delivery vehicle, and its surface can be modified and tailored as a targeted drug delivery system. In this short report, we modified the HNT surface by covalently bonding folic acid (FA and fluorescein isothiocyanate (FITC. The modification of HNTs with folic acid imparts the potential to target tumor cells selectively. The addition of FITC offers a method for quantifying the effectiveness of the FA tagged HNTs ability to target tumor cells. We documented cell uptake of our bi-functionalized HNT (bHNT through phase contrast and epi-fluorescent microscopy. bHNTs showed no signs of cytotoxicity up to a concentration of 150 µg/mL. The increase in cell death with increased bHNT concentration may be due to induced cytotoxicity resulting from intracellular bHNT accumulation that disrupts cellular function leading to cell death. With HNTs recognized as having the ability to serve as both a nanocontainer and nanocarrier, we envision our construct as a potential modular platform for potential use in cancer therapeutics. The HNT interior can be loaded with a variety of anti-cancer drugs (or other chemotherapeutics and serve as a “death cargo” designed to kill cancer cells while providing feedback imaging data on drug efficacy. The surface of the HNT can be modified with gold or silver nanoparticles and used in photothermal therapy by converting light to heat inside tumors. Our HNT-based drug delivery system has the potential to provide localized and targeted therapies that limit or reduce side effects, reduce patient costs and length of hospital stays, and improve quality of life. However, further research is needed to validate the potential of this new

Current possibilities of anti-inflammatory therapy in children with acute respiratory diseases

OpenAIRE

E. E. Lokshina; O. V. Zaytseva

2017-01-01

The paper gives an update on the pathogenesis of acute respiratory diseases, the basis for which is inflammation of the airway mucosal lining. It reflects the results of a comparative clinical trial of the efficacy and safety of the anti-inflammatory drug fenspiride used in the combination therapy for respiratory diseases in children. The findings allow one to recommend the use of fenspiride to treat this condition in children.

Current possibilities of anti-inflammatory therapy in children with acute respiratory diseases

Directory of Open Access Journals (Sweden)

E. E. Lokshina

2017-01-01

Full Text Available The paper gives an update on the pathogenesis of acute respiratory diseases, the basis for which is inflammation of the airway mucosal lining. It reflects the results of a comparative clinical trial of the efficacy and safety of the anti-inflammatory drug fenspiride used in the combination therapy for respiratory diseases in children. The findings allow one to recommend the use of fenspiride to treat this condition in children.

Conservative Nonhormonal Options for the Treatment of Male Infertility: Antibiotics, Anti-Inflammatory Drugs, and Antioxidants.

Science.gov (United States)

Calogero, Aldo E; Condorelli, Rosita A; Russo, Giorgio Ivan; La Vignera, Sandro

2017-01-01

The nonhormonal medical treatment can be divided into empirical, when the cause has not been identified, and nonempirical, if the pathogenic mechanism causing male infertility can be solved or ameliorated. The empirical nonhormonal medical treatment has been proposed for patients with idiopathic or noncurable oligoasthenoteratozoospermia and for normozoospermic infertile patients. Anti-inflammatory, fibrinolytic, and antioxidant compounds, oligo elements, and vitamin supplementation may be prescribed. Infection, inflammation, and/or increased oxidative stress often require a specific treatment with antibiotics, anti-inflammatory drugs, and/or antioxidants. Combined therapies can contribute to improve sperm quality.

Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug

OpenAIRE

Dang, Tram T.; Thai, Anh V.; Cohen, Joshua; Slosberg, Jeremy E.; Siniakowicz, Karolina; Doloff, Joshua C.; Ma, Minglin; Hollister-Lock, Jennifer; Tang, Katherine; Gu, Zhen; Cheng, Hao; Weir, Gordon C.; Langer, Robert; Anderson, Daniel G.

2013-01-01

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising...

Anti-osteoporosis drug use

DEFF Research Database (Denmark)

Hoff, M.; Skurtveit, S.; Meyer, H. E.

2018-01-01

Summary: Use of anti-osteoporotic drugs (AODs) was examined in a Norwegian population 50–85 years. Among them with Fracture Risk Assessment Tool (FRAX) score for major osteoporotic fracture ≥ 20, 25% of the women and 17% of the men received AODs. The strongest predictors for AODs were high age in...

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs

Energy Technology Data Exchange (ETDEWEB)

Kumar, Raj [School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Siril, Prem Felix, E-mail: prem@iitmandi.ac.in [School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Javid, Farideh [School of Applied Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH (United Kingdom)

2016-12-01

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used pharmaceuticals worldwide. Interestingly, many of them have significant anticancer properties too. However, the poor water solubility of certain NSAIDs limits their application for cancer treatment. Nanosizing of such drugs can help to improve the solubility and this may result in enhanced anticancer activities too. Moreover, over dosages and the accompanying side effects of NSAIDs can be minimized by improving their solubility and bioavailability. Successful nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen (NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI) method is reported here. Three water soluble and biocompatible polymers: polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles having spherical morphology with average size below 30 nm were thoroughly characterized using dynamic light scattering and field emission scanning electron microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold improvements in the solubility and significant enhancement in the in-vitro drug release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs against five different cancer cell lines such as MCF-7 (Human breast cancer cell line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell line) A2780 was performed. All the nanoformulated samples showed improved anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP was more than twice that of doxorubicin which is a standard anticancer drug. - Highlights: • Nanoparticles of three non-steroidal anti-inflammatory drugs were prepared. • Particle sizes were

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs

International Nuclear Information System (INIS)

Kumar, Raj; Siril, Prem Felix; Javid, Farideh

2016-01-01

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used pharmaceuticals worldwide. Interestingly, many of them have significant anticancer properties too. However, the poor water solubility of certain NSAIDs limits their application for cancer treatment. Nanosizing of such drugs can help to improve the solubility and this may result in enhanced anticancer activities too. Moreover, over dosages and the accompanying side effects of NSAIDs can be minimized by improving their solubility and bioavailability. Successful nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen (NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI) method is reported here. Three water soluble and biocompatible polymers: polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles having spherical morphology with average size below 30 nm were thoroughly characterized using dynamic light scattering and field emission scanning electron microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold improvements in the solubility and significant enhancement in the in-vitro drug release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs against five different cancer cell lines such as MCF-7 (Human breast cancer cell line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell line) A2780 was performed. All the nanoformulated samples showed improved anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP was more than twice that of doxorubicin which is a standard anticancer drug. - Highlights: • Nanoparticles of three non-steroidal anti-inflammatory drugs were prepared. • Particle sizes were

Effectiveness and Safety of Immunomodulators with Anti-TNF Therapy in Crohn's Disease

Science.gov (United States)

Osterman, Mark T.; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M.; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R.; Lewis, James D.

2015-01-01

Background & Aims The benefit of continuing immunomodulators when “stepping up” to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. Methods We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared using 3 metrics of effectiveness – surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery – and 2 metrics of safety – serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Results Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as “step up” after thiopurine therapy. The rates of surgery (hazard ratio [HR] 1.20, 95% CI 0.73-1.96), hospitalization (HR 0.82 [0.57-1.19]), discontinuation of anti-TNF therapy or surgery (HR 1.09, [0.88-1.34]), and serious infection (HR 0.93 [0.88-1.34]) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risk of opportunistic infection (HR 2.64 [1.21-5.73]) and herpes zoster (HR 3.16 [1.25-7.97]) were increased with combination therapy. Conclusions We found that continuation of immunomodulators after “stepping up” to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. PMID:25724699

Non-Steroidal Anti Inflammatory Drugs Usage In Orthopaedics And ...

African Journals Online (AJOL)

Background: Non steroidal anti-inflammatory drugs NSAIDs) are a group of heterogeneous compounds with nti inflammatory, analgesic and often times anti pyretic roperties. They are weak organic acids and are the most commonly used drugs in Orthopaedic/Trauma practice. hey provide mild to moderate pain relief.

Thyroid uptake of I-131 during anti-thyroid drug treatment

International Nuclear Information System (INIS)

Hoque, M.; Alam, F.; Haque, F.S.; Karim, M.A.; Fariduddin, M.

2004-01-01

Hyperthyroidism is a global ailment and its treatment is very promising either by ant-thyroid drug or by radioiodine. Iodine-131 uptake test is very important for evaluation of hyperthyroid in respect to its therapy and to exclude thyroiditis. This study was performed to observe the thyroid uptake pattern during intake of anti-thyroid medicine and workout the possibility to start I-131 therapy just after withdraw of antithyroid drug without waiting few days. In this study total 252 patient's I-131 uptake test is performed. Among the patient 135 (53.57%) were female, 117 (64.43%) were male. All this patients were hyperthyroid both clinically and biochemically. Thyroid uptake was taken to all patients at 24 hours after oral administration of 5 to 10 micro-curie of I -131. Uptake was taken by an uptake system and recorded as percentage uptake. These patients are grouped into three categories. Group-A-newly diagnosed cases, who have not taken antithyroid drug or I-131 therapy, there were 82 patients in this group, and their mean uptake was 37.12 ±18.5%. Group B - this group of patients were studied during intake of antithyroid medicine, there were 130 patients in this group and their mean uptake was 34.34±16.0%. Group-B patients were further divided in two sub-groups, patients having antithyroid drug for 1 to 3 weeks (group-B 1), group B1 have mean uptake 37±21% and those were taking antithyroid for 3 weeks to 2 years (group-B2), group B2 have uptake 34.34±20%. Group C- these patients are taken from those patients who had withdrawn antithyroid drug for 3 days to 3 months, there were 40 such patients. Group C further divided into two sub-group, group-C1 (stopped for 3-10 days) and group C2 (stopped for 11 days to 3 months). Group C1 had mean uptake 38±16% and group C2 had mean uptake 35±19%. From this study it is observed that Iodine-131 uptake percentage of untreated hyperthyroid; during antithyroid drug treatment and after withdraw of antithyroid drug almost

Advancements in anti-inflammatory therapy for dry eye syndrome.

Science.gov (United States)

McCabe, Erin; Narayanan, Srihari

2009-10-01

The goal of this literature review is to discuss recent discoveries in the pathophysiology of dry eye and the subsequent evolution of diagnostic and management techniques. The mechanisms of various anti-inflammatory treatments are reviewed, and the efficacy of common pharmacologic agents is assessed. Anti-inflammatory therapy is evaluated in terms of its primary indications, target population, and utility within a clinical setting. The Medline PubMed database and the World Wide Web were searched for current information regarding dry eye prevalence, pathogenesis, diagnosis, and management. After an analysis of the literature, major concepts were integrated to generate an updated portrayal of the status of dry eye syndrome. Inflammation appears to play a key role in perpetuating and sustaining dry eye. Discoveries of inflammatory markers found within the corneal and conjunctival epithelium of dry eye patients have triggered recent advancements in therapy. Pharmacologic anti-inflammatory therapy for dry eye includes 2 major categories: corticosteroids and immunomodulatory agents. Fatty acid and androgen supplementation and oral antibiotics have also shown promise in dry eye therapy because of their anti-inflammatory effects. Anti-inflammatory pharmacologic agents have shown great success in patients with moderate to severe dry eye when compared with alternative treatment modalities. A deeper understanding of the link between inflammation and dry eye validates the utilization of anti-inflammatory therapy in everyday optometric practice.

Poisoning by anti-malarial drugs

African Journals Online (AJOL)

had taken chloroquine: no other anti-malarial drugs were involved [1]. ... and angio-oedema have been described. Itching without a ... 15mg/L the risk of permanent visual damage and cardiac dysrhythmias is ... to use an alternative method.

Identifying rapidly parasiticidal anti-malarial drugs using a simple and reliable in vitro parasite viability fast assay.

Science.gov (United States)

Linares, María; Viera, Sara; Crespo, Benigno; Franco, Virginia; Gómez-Lorenzo, María G; Jiménez-Díaz, María Belén; Angulo-Barturen, Íñigo; Sanz, Laura María; Gamo, Francisco-Javier

2015-11-05

The emergence of Plasmodium falciparum resistance to artemisinins threatens to undermine the effectiveness of artemisinin-based combination anti-malarial therapy. Developing suitable drugs to replace artemisinins requires the identification of new compounds that display rapid parasite killing kinetics. However, no current methods fully meet the requirements to screen large compound libraries for candidates with such properties. This study describes the development and validation of an in vitro parasite viability fast assay for identifying rapidly parasiticidal anti-malarial drugs. Parasite killing kinetics were determined by first culturing unlabelled erythrocytes with P. falciparum in the presence of anti-malarial drugs for 24 or 48 h. After removing the drug, samples were added to erythrocytes pre-labelled with intracellular dye to allow their subsequent identification. The ability of viable parasites to re-establish infection in labelled erythrocytes could then be detected by two-colour flow cytometry after tagging of parasite DNA. Thus, double-stained erythrocytes (with the pre-labelled intracellular dye and the parasite DNA dye) result only after establishment of new infections by surviving parasites. The capacity of the test anti-malarial drugs to eliminate viable parasites within 24 or 48 h could, therefore, be determined. The parasite viability fast assay could be completed within 48 h following drug treatment and distinguished between rapidly parasiticidal anti-malarial drugs versus those acting more slowly. The assay was validated against ten standard anti-malarial agents with known properties and results correlated well with established methods. An abbreviated assay, suitable for adaption to medium-high throughput screening, was validated and applied against a set of 20 compounds retrieved from the publically available Medicines for Malaria Venture 'Malaria Box'. The quantification of new infections to determine parasite viability offers important

Observation and Analysis of Anti-cancer Drug Use and Dose ...

African Journals Online (AJOL)

As all anti-cancer drugs are of narrow therapeutic window so dose individualization is required to be done. A study was conducted to check the use of anti-cancer drugs in the local anti-cancer facility of Bahawalpur i.e. Bahawalpur Institute of Nuclear Medicine and Oncology (BINO). In this study, the dose individualization ...

In vivo mitochondrial function in HIV-infected persons treated with contemporary anti-retroviral therapy: a magnetic resonance spectroscopy study.

Directory of Open Access Journals (Sweden)

Brendan A I Payne

Full Text Available Modern anti-retroviral therapy is highly effective at suppressing viral replication and restoring immune function in HIV-infected persons. However, such individuals show reduced physiological performance and increased frailty compared with age-matched uninfected persons. Contemporary anti-retroviral therapy is thought to be largely free from neuromuscular complications, whereas several anti-retroviral drugs previously in common usage have been associated with mitochondrial toxicity. It has recently been established that patients with prior exposure to such drugs exhibit irreversible cellular and molecular mitochondrial defects. However the functional significance of such damage remains unknown. Here we use phosphorus magnetic resonance spectroscopy ((31P-MRS to measure in vivo muscle mitochondrial oxidative function, in patients treated with contemporary anti-retroviral therapy, and compare with biopsy findings (cytochrome c oxidase (COX histochemistry. We show that dynamic oxidative function (post-exertional ATP (adenosine triphosphate resynthesis was largely maintained in the face of mild to moderate COX defects (affecting up to ∼10% of fibers: τ½ ADP (half-life of adenosine diphosphate clearance, HIV-infected 22.1±9.9 s, HIV-uninfected 18.8±4.4 s, p = 0.09. In contrast, HIV-infected patients had a significant derangement of resting state ATP metabolism compared with controls: ADP/ATP ratio, HIV-infected 1.24±0.08×10(-3, HIV-uninfected 1.16±0.05×10(-3, p = 0.001. These observations are broadly reassuring in that they suggest that in vivo mitochondrial function in patients on contemporary anti-retroviral therapy is largely maintained at the whole organ level, despite histochemical (COX defects within individual cells. Basal energy requirements may nevertheless be increased.

Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients: a nationwide register-based study in Denmark.

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Lødrup, A; Pottegård, A; Hallas, J; Bytzer, P

2015-07-01

Guidelines recommend that patients with gastro-oesophageal reflux disease are adequately treated with acid-suppressive therapy before undergoing anti-reflux surgery. Little is known of the use of acid-suppressive drugs before anti-reflux surgery. To determine the use of proton pump inhibitors and H2 -receptor antagonists in the year before anti-reflux surgery. A nationwide retrospective study of all patients aged ≥18 undergoing first-time anti-reflux surgery in Denmark during 2000-2012 using data from three different sources: the Danish National Register of Patients, the Danish National Prescription Register, and the Danish Person Register. The study population thus included 2922 patients (median age: 48 years, 55.7% male). The annual proportion of patients redeeming ≥180 DDD of acid-suppressive therapy increased from 17.0% 5 years before anti-reflux surgery to 64.9% 1 year before. The probability for inadequate dosing 1 year before surgery (reflux surgery, as a high proportion of patients receive inadequate dosing of acid-suppressive therapy prior to the operation. © 2015 John Wiley & Sons Ltd.

Pneumophonic coordination impairments in parkinsonian dysarthria: importance of aerodynamic parameters measurements.

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Moustapha, S M; Alain, G; Robert, E; Bernard, T; Mourtalla, Kâ M; Lamine, G; François, V

2012-01-01

Among Parkinsonian axial signs, dysarthria represents an important disabling symptom able to lead towards a significant reduction of oral communication. Several methods of dysarthria assessment have been used but aerodynamic evaluation is rare in the literature. To highlight the importance of aerodynamic parameters measurements in assessment of parkinsonian dysarthria. Using a dedicated system (EVA2), 24 parkinsonian patients were recorded after withdrawal of L-dopa for at least 12 h (condition called OFF DOPA) in order to evaluate intra-oral pressure (IOP), mean oral air flow (MOAF) and laryngeal resistance (LR) on six /p/ during realization of the sentence "Papa ne m'a pas parle' de beau-papa" ("Daddy did not speak to me about daddy-in-law") which corresponds to a breath group. 50 control subjects were recorded in parallel in order to define reference measurements. It appeared that there is in Parkinson's disease aerodynamic impairments which were evidenced by the fall in IOP and that of MOAF in patients compared with control subjects. The difference between the two groups was statistically significant. In addition a greater instability of LR in patients compared with control subjects was also noted. Our results show that measurements of aerodynamics parameters, by reflecting the dysfunction induced by disease, may well be relevant factors in parkinsonian dysarthria evaluation.

Systems modeling of anti-apoptotic pathways in prostate cancer: psychological stress triggers a synergism pattern switch in drug combination therapy.

Directory of Open Access Journals (Sweden)

Xiaoqiang Sun

Full Text Available Prostate cancer patients often have increased levels of psychological stress or anxiety, but the molecular mechanisms underlying the interaction between psychological stress and prostate cancer as well as therapy resistance have been rarely studied and remain poorly understood. Recent reports show that stress inhibits apoptosis in prostate cancer cells via epinephrine/beta2 adrenergic receptor/PKA/BAD pathway. In this study, we used experimental data on the signaling pathways that control BAD phosphorylation to build a dynamic network model of apoptosis regulation in prostate cancer cells. We then compared the predictive power of two different models with or without the role of Mcl-1, which justified the role of Mcl-1 stabilization in anti-apoptotic effects of emotional stress. Based on the selected model, we examined and quantitatively evaluated the induction of apoptosis by drug combination therapies. We predicted that the combination of PI3K inhibitor LY294002 and inhibition of BAD phosphorylation at S112 would produce the best synergistic effect among 8 interventions examined. Experimental validation confirmed the effectiveness of our predictive model. Moreover, we found that epinephrine signaling changes the synergism pattern and decreases efficacy of combination therapy. The molecular mechanisms responsible for therapeutic resistance and the switch in synergism were explored by analyzing a network model of signaling pathways affected by psychological stress. These results provide insights into the mechanisms of psychological stress signaling in therapy-resistant cancer, and indicate the potential benefit of reducing psychological stress in designing more effective therapies for prostate cancer patients.

The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

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Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

2011-10-01

described not only the unique mechanism of selective ER modulator (SERM)-stimulated breast cancer growth, but also a new apoptotic biology of oestradiol action in breast cancer, following 5 years of anti-hormonal treatment. Oestradiol-induced apoptotic therapy is currently shown to be successful for the short-term treatment of metastatic ER positive breast cancer following exhaustive treatment with anti-hormones. The "oestrogen purge" concept is now being integrated into trials of long-term adjuvant anti-hormone therapy. The Study of Letrazole Extension (SOLE) trial employs "anti-hormonal drug holidays" so that a woman's own oestrogen may periodically purge and kill the nascent sensitized breast cancer cells that are developing. This is the translation of an idea first proposed at the 1992 St. Gallen Conference. Although tamoxifen is the first successful targeted therapy in cancer, the pioneering medicine is more than that. A study of the pharmacology of tamoxifen opened the door for a pioneering application in cancer chemoprevention and created a new drug group: the SERMs, with group members (raloxifene and lasofoxifene) approved for the treatment and prevention of osteoporosis with a simultaneous reduction of breast cancer risk. Thus, the combined strategies of long-term anti-hormone adjuvant therapy, targeted to the breast tumour ER, coupled with the expanding use of SERMs to prevent osteoporosis and prevent breast cancer as a beneficial side effect, have advanced patient survivorship significantly and promise to reduce breast cancer incidence. Copyright © 2011 Elsevier Ltd. All rights reserved.

The nature of tremor circuits in parkinsonian and essential tremor

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Cagnan, Hayriye; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Cheeran, Binith; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

2014-01-01

Tremor is a cardinal feature of Parkinson’s disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient’s own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson’s disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50–77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34–74 years). Stimulation at near-to tremor frequency entrained tremor in all three patient groups (ventrolateral thalamic stimulation in Parkinson’s disease, P = 0.0078, subthalamic stimulation in Parkinson’s disease, P = 0.0312; ventrolateral thalamic stimulation in essential tremor, P = 0.0137; two-tailed paired Wilcoxon signed-rank tests). However, only ventrolateral thalamic stimulation in essential tremor modulated postural tremor amplitude according to the timing of stimulation pulses with respect to the tremor cycle (e.g. P = 0.0002 for tremor amplification, two-tailed Wilcoxon rank sum test). Parkinsonian rest and essential postural tremor severity (i.e. tremor amplitude) differed in their relative tolerance to spontaneous changes in tremor frequency when stimulation was not applied. Specifically, the amplitude of parkinsonian rest tremor remained unchanged despite spontaneous changes in tremor frequency, whereas that of essential postural tremor reduced when tremor frequency departed from median values. Based on these results we conclude that

Classifying new anti-tuberculosis drugs: rationale and future perspectives

Directory of Open Access Journals (Sweden)

Simon Tiberi

2017-03-01

Full Text Available The classification of anti-tuberculosis (TB drugs is important as it helps the clinician to build an appropriate anti-TB regimen for multidrug-resistant (MDR and extensively drug-resistant (XDR TB cases that do not fulfil the criteria for the shorter MDR-TB regimen. The World Health Organization (WHO has recently approved a revision of the classification of new anti-TB drugs based on current evidence on each drug. In the previous WHO guidelines, the choice of drugs was based on efficacy and toxicity in a step-down manner, from group 1 first-line drugs and groups 2–5 second-line drugs, to group 5 drugs with potentially limited efficacy or limited clinical evidence. In the revised WHO classification, exclusively aimed at managing drug-resistant cases, medicines are again listed in hierarchical order from group A to group D. In parallel, a possible future classification is independently proposed. The aim of this viewpoint article is to describe the evolution in WHO TB classification (taking into account an independently proposed new classification and recent changes in WHO guidance, while commenting on the differences between them. The latest evidence on the ex-group 5 drugs is also discussed.

Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal anti-inflammatory drugs?

OpenAIRE

Gibelin, Aude; de Prost, Nicolas; Brun-Buisson, Christian

2013-01-01

Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia in immunocompetent adults that has recently been reported to occur following administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report herein the case of a 24-year-old patient with no predisposing risk factor who developed a lung abscess after NSAIDs exposure, further illustrating this potentially severe complication of NSAIDs use, especially in the absence of associated antibiotic therapy.

Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal anti-inflammatory drugs?

Science.gov (United States)

Gibelin, Aude; de Prost, Nicolas; Brun-Buisson, Christian

2013-08-20

Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia in immunocompetent adults that has recently been reported to occur following administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report herein the case of a 24-year-old patient with no predisposing risk factor who developed a lung abscess after NSAIDs exposure, further illustrating this potentially severe complication of NSAIDs use, especially in the absence of associated antibiotic therapy.

Curcumin as a clinically-promising anti-cancer agent: pharmacokinetics and drug interactions.

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Adiwidjaja, Jeffry; McLachlan, Andrew J; Boddy, Alan V

2017-09-01

Curcumin has been extensively studied for its anti-cancer properties. While a diverse array of in vitro and preclinical research support the prospect of curcumin use as an anti-cancer therapeutic, most human studies have failed to meet the intended clinical expectation. Poor systemic availability of orally-administered curcumin may account for this disparity. Areas covered: This descriptive review aims to concisely summarise available clinical studies investigating curcumin pharmacokinetics when administered in different formulations. A critical analysis of pharmacokinetic- and pharmacodynamic-based interactions of curcumin with concomitantly administered drugs is also provided. Expert opinion: The encouraging clinical results of curcumin administration are currently limited to people with colorectal cancer, given that sufficient curcumin concentrations persist in colonic mucosa. Higher parent curcumin systemic exposure, which can be achieved by several newer formulations, has important implications for optimal treatment of cancers other than those in gastrointestinal tract. Curcumin-drug pharmacokinetic interactions are also almost exclusively in the enterocytes, owing to extensive first pass metabolism and poor curcumin bioavailability. Greater scope of these interactions, i.e. modulation of the systemic elimination of co-administered drugs, may be expected from more-bioavailable curcumin formulations. Further studies are still warranted, especially with newer formulations to support the inclusion of curcumin in cancer therapy regimens.

Anti-osteoporotic therapy in Denmark-predictors and demographics of poor refill compliance and poor persistence

DEFF Research Database (Denmark)

Hansen, C; Pedersen, Birthe D.; Konradsen, H

2013-01-01

In this study of 100,949 new users of oral bisphosphonates age ≥35 years, "early quitters" were found to differ from others with poor refill compliance in terms of socioeconomic, demographic, and treatment-related characteristics. New risk factors for poor compliance and persistence were identified...... quitters" were associated with high household income, subjects' age 71.9-79 years, living in the countryside or village, prior treatment with analgesics and anti-parkinson drugs, and dementia. Differences concerning decreased risk of "early quitters" were associated with male, living in an apartment......, children living at home, living close to a university hospital, anti-osteoporotic therapy other than alendronate, number of drugs especially above three, pulmonary disease, collagen disease. CONCLUSION: The results suggest a need for improved support for patients to facilitate the interpretation...

Drug therapy in spinal tuberculosis.

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Rajasekaran, S; Khandelwal, Gaurav

2013-06-01

Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and hence is included in Category I of the WHO classification. The tuberculosis bacilli isolated from patients are of four different types with different growth kinetics and metabolic characteristics. Hence multiple drugs, which act on the different groups of the mycobacteria, are included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted chemotherapy (which may be 'short course' and 'intermittent' but preferably 'directly observed') is effective in controlling the infection. Spinal Multi-drug-resistant TB and spinal TB in HIV-positive patients present unique problems in management and have much poorer prognosis. Failure of chemotherapy and emergence of drug resistance are frequent due to the failure of compliance hence all efforts must be made to improve patient compliance to the prescribed drug regimen.

Non-steroidal anti-inflammatory drugs and cyclooxygenase in Alzheimer's disease

NARCIS (Netherlands)

Hoozemans, Jeroen J. M.; Veerhuis, Robert; Rozemuller, Annemieke J. M.; Eikelenboom, Piet

2003-01-01

Epidemiological studies indicate that anti-inflammatory drugs, especially the non-steroidal anti-inflammatory drugs (NSAIDs), decrease the risk of developing Alzheimer's disease (AD). Their beneficial effects may be due to interference in the chronic inflammatory reaction, that takes place in AD.

The production and sales of anti-tuberculosis drugs in China.

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Huang, Yang-Mu; Zhao, Qi-Peng; Ren, Qiao-Meng; Peng, Dan-Lu; Guo, Yan

2016-10-04

Tuberculosis (TB) is a major infectious disease globally. Adequate and proper use of anti-TB drugs is essential for TB control. This study aims to study China's production capacity and sales situation of anti-TB drugs, and to further discuss the potential for China to contribute to global TB control. The production data of anti-TB drugs in China from 2011 to 2013 and the sales data from 2010 to 2014 were extracted from Ministry of Industry and Information Technology database of China and IMS Health database, respectively. The number of drugs was standardized to the molecular level of the key components before calculating. All data were described and analyzed by Microsoft Excel. First-line drugs were the majority in both sales (89.5 %) and production (92.3 %) of anti-TB drugs in China. The production of rifampicin held the majority share in active pharmaceutical ingredients (APIs) and finished products, whilst ethambutol and pyrazinamide were the top two sales in finished products. Fixed-dose combinations only held small percentages in total production and sales weight, though a slight increase was observed. The production and sales of streptomycin showed a tendency of decrease after 2012. The trends and proportion of different anti-TB drugs were similar in production and sales, however, the production weight was much larger than that of sales, especially for rifampicin and isoniazid. First-line drugs were the predominant medicine produced and used in China. While the low production and sales of the second-line TB drugs and FDCs rose concerns for the treatment of multiple drug resistant TB. The redundant production amount, as well as the prompt influence of national policy on drug production and sales, indicated the potential for China to better contribute to global TB control.

Pneumophonic Coordination Impairments in Parkinsonian Dysarthria

African Journals Online (AJOL)

Patients and Methods: Using a dedicated system (EVA2), 24 parkinsonian patients were recorded after withdrawal of Ldopa for at least 12 h (condition called OFF DOPA) in order to evaluate intra-oral pressure (IOP), mean oral air flow (MOAF) and laryngeal resistance (LR) on six /p/ during realization of the sentence ''Papa ...

The peri-operative management of anti-platelet therapy in elective, non-cardiac surgery.

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Alcock, Richard F; Naoum, Chris; Aliprandi-Costa, Bernadette; Hillis, Graham S; Brieger, David B

2013-07-31

Cardiovascular complications are important causes of morbidity and mortality in patients undergoing elective non-cardiac surgery, with adverse cardiac outcomes estimated to occur in approximately 4% of all patients. Anti-platelet therapy withdrawal may precede up to 10% of acute cardiovascular syndromes, with withdrawal in the peri-operative setting incompletely appraised. The aims of our study were to determine the proportion of patients undergoing elective non-cardiac surgery currently prescribed anti-platelet therapy, and identify current practice in peri-operative management. In addition, the relationship between management of anti-platelet therapy and peri-operative cardiac risk was assessed. We evaluated consecutive patients attending elective non-cardiac surgery at a major tertiary referral centre. Clinical and biochemical data were collected and analysed on patients currently prescribed anti-platelet therapy. Peri-operative management of anti-platelet therapy was compared with estimated peri-operative cardiac risk. Included were 2950 consecutive patients, with 516 (17%) prescribed anti-platelet therapy, primarily for ischaemic heart disease. Two hundred and eighty nine (56%) patients had all anti-platelet therapy ceased in the peri-operative period, including 49% of patients with ischaemic heart disease and 46% of patients with previous coronary stenting. Peri-operative cardiac risk score did not influence anti-platelet therapy management. Approximately 17% of patients undergoing elective non-cardiac surgery are prescribed anti-platelet therapy, the predominant indication being for ischaemic heart disease. Almost half of all patients with previous coronary stenting had no anti-platelet therapy during the peri-operative period. The decision to cease anti-platelet therapy, which occurred commonly, did not appear to be guided by peri-operative cardiac risk stratification. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Algorithms for optimizing drug therapy

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Martin Lene

2004-07-01

Full Text Available Abstract Background Drug therapy has become increasingly efficient, with more drugs available for treatment of an ever-growing number of conditions. Yet, drug use is reported to be sub optimal in several aspects, such as dosage, patient's adherence and outcome of therapy. The aim of the current study was to investigate the possibility to optimize drug therapy using computer programs, available on the Internet. Methods One hundred and ten officially endorsed text documents, published between 1996 and 2004, containing guidelines for drug therapy in 246 disorders, were analyzed with regard to information about patient-, disease- and drug-related factors and relationships between these factors. This information was used to construct algorithms for identifying optimum treatment in each of the studied disorders. These algorithms were categorized in order to define as few models as possible that still could accommodate the identified factors and the relationships between them. The resulting program prototypes were implemented in HTML (user interface and JavaScript (program logic. Results Three types of algorithms were sufficient for the intended purpose. The simplest type is a list of factors, each of which implies that the particular patient should or should not receive treatment. This is adequate in situations where only one treatment exists. The second type, a more elaborate model, is required when treatment can by provided using drugs from different pharmacological classes and the selection of drug class is dependent on patient characteristics. An easily implemented set of if-then statements was able to manage the identified information in such instances. The third type was needed in the few situations where the selection and dosage of drugs were depending on the degree to which one or more patient-specific factors were present. In these cases the implementation of an established decision model based on fuzzy sets was required. Computer programs

Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug

OpenAIRE

Dang, Tram T.; Thai, Anh V.; Cohen, Joshua; Slosberg, Jeremy E.; Siniakowicz, Karolina; Doloff, Joshua C.; Ma, Minglin; Hollister-Lock, Jennifer; Tang, Katherine M.; Gu, Zhen; Cheng, Hao; Weir, Gordon C.; Langer, Robert; Anderson, Daniel Griffith; Tang, Katherine

2013-01-01

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising...

Recruitment of beta-arrestin2 to the dopamine D2 receptor: insights into anti-psychotic and anti-parkinsonian drug receptor signaling

DEFF Research Database (Denmark)

Klewe, Ib V; Nielsen, Søren M; Tarpø, Louise

2008-01-01

, SNPA all acted as partial agonists with decreasing efficacy in the BRET assay. In contrast, a wide selection of typical and atypical anti-psychotics was incapable of stimulating beta-arrestin2 recruitment to the D2 receptor. Moreover, we observed that haloperidol, sertindole, olanzapine, clozapine...

Plants’ Natural Products as Alternative Promising Anti-Candida Drugs

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Soliman, Sameh; Alnajdy, Dina; El-Keblawy, Ali A.; Mosa, Kareem A.; Khoder, Ghalia; Noreddin, Ayman M.

2017-01-01

Candida is a serious life-threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti-Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system. PMID:28989245

Anti-Aging Drugs - Prospect of Longer Life?

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Klimova, Blanka; Novotny, Michal; Kuca, Kamil

2017-11-29

Aging is a natural part of human life. However, recent discoveries indicate that pharmacological approaches used for the improvement and possibly, for the delay of the aging process, might shed a new light on this topic. This might obviously contribute to the extension of the active life of older people and maintenance of their quality of life, which could consequently reduce both social and economic burden of each country, especially the developed ones. The purpose of this study is to explore pharmacological discoveries which may help to the delay or improvement of the aging process. More specifically, the authors focus on three anti-aging drugs candidates: metformin, rapamycin and resveratrol and one anti-aging component NAD+ precursors whose randomized control trials on animals have appeared to provide some efficacy in this respect and they seem to be promising in the aging process of human beings. This was done by conducting a literature review of available sources describing the issue of aging process with special focus on those anti-aging drug candidates. The results of this study indicate that promising anti-aging candidates seem to be metformin, especially as far as cardiovascular or cancer mortality is concerned, and NAD+ precursors since they appear to promote better organ function, increased physical resistance, disease resistance and prolonged life expectancy. There is a call for more longitudinal clinical trials, which would prove the efficacy of the promising anti-aging drugs candidates in humans. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report

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Stavrinou Lampis C

2011-06-01

Full Text Available Abstract Background The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. Case presentation We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. Conclusion The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report.

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Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E

2011-06-29

The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

The transport of nifurtimox, an anti-trypanosomal drug, in an in vitro model of the human blood-brain barrier: evidence for involvement of breast cancer resistance protein.

Science.gov (United States)

Watson, Christopher P; Dogruel, Murat; Mihoreanu, Larisa; Begley, David J; Weksler, Babette B; Couraud, Pierre O; Romero, Ignacio A; Thomas, Sarah A

2012-02-03

Human African trypanosomiasis (HAT) is a parasitic disease affecting sub-Saharan Africa. The parasites are able to traverse the blood-brain barrier (BBB), which marks stage 2 (S2) of the disease. Delivery of anti-parasitic drugs across the BBB is key to treating S2 effectively and the difficulty in achieving this goal is likely to be a reason why some drugs require highly intensive treatment regimes to be effective. This study aimed to investigate not only the drug transport mechanisms utilised by nifurtimox at the BBB, but also the impact of nifurtimox-eflornithine combination therapy (NECT) and other anti-HAT drug combination therapies (CTs) on radiolabelled-nifurtimox delivery in an in vitro model of drug accumulation and the human BBB, the hCMEC/D3 cell line. We found that nifurtimox appeared to use several membrane transporters, in particular breast-cancer resistance protein (BCRP), to exit the BBB cells. The addition of eflornithine caused no change in the accumulation of nifurtimox, nor did the addition of clinically relevant doses of the other anti-HAT drugs suramin, nifurtimox or melarsoprol, but a significant increase was observed with the addition of pentamidine. The results provide evidence that anti-HAT drugs are interacting with membrane transporters at the human BBB and suggest that combination with known transport inhibitors could potentially improve their efficacy. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular chess? Hallmarks of anti-cancer drug resistance.

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Cree, Ian A; Charlton, Peter

2017-01-05

The development of resistance is a problem shared by both classical chemotherapy and targeted therapy. Patients may respond well at first, but relapse is inevitable for many cancer patients, despite many improvements in drugs and their use over the last 40 years. Resistance to anti-cancer drugs can be acquired by several mechanisms within neoplastic cells, defined as (1) alteration of drug targets, (2) expression of drug pumps, (3) expression of detoxification mechanisms, (4) reduced susceptibility to apoptosis, (5) increased ability to repair DNA damage, and (6) altered proliferation. It is clear, however, that changes in stroma and tumour microenvironment, and local immunity can also contribute to the development of resistance. Cancer cells can and do use several of these mechanisms at one time, and there is considerable heterogeneity between tumours, necessitating an individualised approach to cancer treatment. As tumours are heterogeneous, positive selection of a drug-resistant population could help drive resistance, although acquired resistance cannot simply be viewed as overgrowth of a resistant cancer cell population. The development of such resistance mechanisms can be predicted from pre-existing genomic and proteomic profiles, and there are increasingly sophisticated methods to measure and then tackle these mechanisms in patients. The oncologist is now required to be at least one step ahead of the cancer, a process that can be likened to 'molecular chess'. Thus, as well as an increasing role for predictive biomarkers to clinically stratify patients, it is becoming clear that personalised strategies are required to obtain best results.

Safety and efficacy of anti-tumor necrosis factor α therapy in ten patients with recent-onset refractory reactive arthritis.

Science.gov (United States)

Meyer, Alain; Chatelus, Emmanuel; Wendling, Daniel; Berthelot, Jean-Marie; Dernis, Emmanuelle; Houvenagel, Eric; Morel, Jacques; Richer, Olivier; Schaeverbeke, Thierry; Gottenberg, Jacques-Eric; Sibilia, Jean

2011-05-01

There are few treatments for reactive arthritis (ReA). Since concentrations of tumor necrosis factor α (TNFα) are high in the serum and joints of patients with persistent ReA, this cytokine could be targeted in patients who do not respond to nonsteroidal antiinflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). We under-took this study to investigate the safety and efficacy of TNF antagonists in patients with recent-onset and refractory ReA. All French rheumatology and internal medicine practitioners registered on the Club Rhumatisme et Inflammation web site were asked to report on patients with ReA (defined by the criteria of the Third International Workshop on Reactive Arthritis) who had received anti-TNF therapy within the 12 months following the triggering infection. Tolerance and efficacy were retrospectively assessed using a standardized questionnaire. Ten patients with ReA previously refractory to NSAIDs and DMARDs, for which there was clinical and microbiologic evidence of a triggering bacterial infection, received anti-TNF therapy within a median of 6 months (range 2-12 months) between the beginning of ReA and the initiation of the treatment. The median followup was 20.6 months (range 6-50 months). We observed no severe adverse event and no infection related to the bacterium that triggered the ReA. Anti-TNF therapy was rapidly effective in 9 patients (90%), as shown by the rapid effect on a visual analog scale pain score, tender joint count, swollen joint count, and extraarticular manifestations, and by the corticosteroid-sparing effect. Anti-TNF therapy appears to be a safe and effective treatment of rheumatic and extraarticular manifestations in patients with recent-onset and refractory ReA, with a corticosteroid-sparing effect. Thus, TNFα could be a relevant target for ReA therapy.

Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

Directory of Open Access Journals (Sweden)

Han-Chung Wu

2010-01-01

Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

A Novel Method for Determining the Inhibitory Potential of Anti-HIV Drugs

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Shen, Lin; Rabi, S. Alireza; Siliciano, Robert F.

2009-01-01

In the absence of a cure, most HIV-1-infected individuals will require life-long treatment. It is therefore essential to optimize highly active antiretroviral therapy. Recent research has shown that the slope parameter or Hill coefficient, which describes the steepness of a dose-response curve, is a critical missing dimension in the evaluation of antiviral drug activity. Based on this finding, the instantaneous inhibitory potential (IIP) has been derived as a new measure of antiviral drug activity. IIP incorporates the slope parameter and thus is a more accurate pharmacodynamic measure of antiviral activity than current measures such as IC50 and inhibitory quotient. However, it remains important to determine how to use IIP to predict the in vivo efficacy of anti-HIV-1 drugs. This article discusses recent advances in in vitro measures of antiviral activity and the therapeutic implications of the dose-response curve slope and IIP. PMID:19837466

Genomic and post-genomic effects of anti-glaucoma drugs preservatives in trabecular meshwork

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Izzotti, Alberto, E-mail: izzotti@unige.it [Mutagenesis Unit, IRCCS AOU San Martino – IST, Genova (Italy); Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa (Italy); La Maestra, Sebastiano; Micale, Rosanna Tindara; Longobardi, Maria Grazia [Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa (Italy); Saccà, Sergio Claudio [Ophthalmology Unit, IRCCS AOU San Martino-IST, Genova (Italy)

2015-02-15

Highlights: • Glaucoma drug preservatives induce DNA damage in trabecular meshwork cells. • Cellular alteration is related with the occurrence of activation of apoptosis through the intrinsic pathway. • Drug preservatives unable to induce cell damage are ineffective in killing bacteria. • Anti glaucoma drugs should be formulated as single-dose usage devoid of genotoxic preservatives. - Abstract: Oxidative stress plays an important role in glaucoma. Some preservatives of anti-glaucoma drugs, commonly used in glaucoma therapy, can prevent or induce oxidative stress in the trabecular meshwork. The aim of this study is to evaluate cellular and molecular damage induced in trabecular meshwork by preservatives contained in anti-glaucoma drugs. Cell viability (MTT test), DNA fragmentation (Comet test), oxidative DNA damage (8-oxo-dG), and gene expression (cDNA microarray) have been evaluated in trabecular meshwork specimens and in human trabecular meshwork cells treated with benzalkonium chloride, polyQuad, purite, and sofzia-like mixture. Moreover, antimicrobial effectiveness and safety of preservative contents in drugs was tested. In ex vivo experiments, benzalkonium chloride and polyQuad induced high level of DNA damage in trabecular meshwork specimens, while the effect of purite and sofzia were more attenuated. The level of DNA fragmentation induced by benzalkonium chloride was 2.4-fold higher in subjects older than 50 years than in younger subjects. Benzalkonium chloride, and polyQuad significantly increased oxidative DNA damage as compared to sham-treated specimens. Gene expression was altered by benzalkonium chloride, polyQuad, and purite but not by sofzia. In in vitro experiments, benzalkonium chloride and polyQuad dramatically decreased trabecular meshwork cell viability, increased DNA fragmentation, and altered gene expression. A lesser effect was also exerted by purite and sofzia. Genes targeted by these alterations included Fas and effector caspase-3

Non-steroidal anti-inflammatory drugs and benign oesophageal stricture.

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Heller, S R; Fellows, I W; Ogilvie, A L; Atkinson, M

1982-01-01

Drug histories were obtained from 76 patients at the time of initial Eder-Puestow dilatation for benign oesophageal stricture. Six patients had consumed drugs known to cause oesophageal ulceration (emepronium bromide and potassium preparations). Of the remaining 70 patients, 22 had regularly taken a non-steroidal anti-inflammatory drug before the onset of dysphagia compared with 10 patients in a control group matched for age and sex; this difference was significant (p less than 0.02). Non-steroidal anti-inflammatory drugs may have a causative role in the formation of oesophageal stricture in patients with gastro-oesophageal reflux, in whom they should be prescribed with caution. PMID:6807392

Anti-inflammatory drugs and psychosis

NARCIS (Netherlands)

Laan, W.

2008-01-01

This thesis focuses on the disorder we know as schizophrenia. Although there is treatment for schizophrenia in the form of anti-psychotic drugs, not all patients respond well to this treatment. A large part of patients will have remaining symptoms for the rest of their lives. A number of hypotheses

Anti-calmodulins and tricyclic adjuvants in pain therapy block the TRPV1 channel.

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Zoltán Oláh

2007-06-01

Full Text Available Ca(2+-loaded calmodulin normally inhibits multiple Ca(2+-channels upon dangerous elevation of intracellular Ca(2+ and protects cells from Ca(2+-cytotoxicity, so blocking of calmodulin should theoretically lead to uncontrolled elevation of intracellular Ca(2+. Paradoxically, classical anti-psychotic, anti-calmodulin drugs were noted here to inhibit Ca(2+-uptake via the vanilloid inducible Ca(2+-channel/inflamatory pain receptor 1 (TRPV1, which suggests that calmodulin inhibitors may block pore formation and Ca(2+ entry. Functional assays on TRPV1 expressing cells support direct, dose-dependent inhibition of vanilloid-induced (45Ca(2+-uptake at microM concentrations: calmidazolium (broad range > or = trifluoperazine (narrow range chlorpromazine/amitriptyline>fluphenazine>>W-7 and W-13 (only partially. Most likely a short acidic domain at the pore loop of the channel orifice functions as binding site either for Ca(2+ or anti-calmodulin drugs. Camstatin, a selective peptide blocker of calmodulin, inhibits vanilloid-induced Ca(2+-uptake in intact TRPV1(+ cells, and suggests an extracellular site of inhibition. TRPV1(+, inflammatory pain-conferring nociceptive neurons from sensory ganglia, were blocked by various anti-psychotic and anti-calmodulin drugs. Among them, calmidazolium, the most effective calmodulin agonist, blocked Ca(2+-entry by a non-competitive kinetics, affecting the TRPV1 at a different site than the vanilloid binding pocket. Data suggest that various calmodulin antagonists dock to an extracellular site, not found in other Ca(2+-channels. Calmodulin antagonist-evoked inhibition of TRPV1 and NMDA receptors/Ca(2+-channels was validated by microiontophoresis of calmidazolium to laminectomised rat monitored with extracellular single unit recordings in vivo. These unexpected findings may explain empirically noted efficacy of clinical pain adjuvant therapy that justify efforts to develop hits into painkillers, selective to sensory Ca(2

Contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients on nonsteroidal anti-inflammatory drugs, antiplatelet agents, anticoagulants, corticosteroids and selective serotonin reuptake inhibitors.

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Venerito, M; Schneider, C; Costanzo, R; Breja, R; Röhl, F-W; Malfertheiner, P

2018-06-01

Nonsteroidal anti-inflammatory drugs, low-dose aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and corticosteroids increase the risk of gastroduodenal bleeding. To determine in a retrospective cohort study the contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients taking these drugs. Among patients with peptic ulcer disease diagnosed by endoscopy from 01/2004 to 12/2014 (N = 1719, 60% males, age 65.8 ± 14.5), 56.9% had peptic ulcer bleeding (cases) and 43.1% uncomplicated peptic ulcer disease (controls). Demographics, intake of nonsteroidal anti-inflammatory drugs, aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors, proton pump inhibitors and corticosteroids were documented. H. pylori status was determined by histology, rapid urease test or serology. Adjusted odds ratios (OR) were estimated by logistic regression analysis. Helicobacter pylori infection increased the risk of peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users (OR = 2.91, 95% CI = 1.71-4.98 and OR = 2.23, 95% CI = 1.52-3.28, respectively), but not in patients on anticoagulants, selective serotonin reuptake inhibitor or corticosteroid therapy. H. pylori-positive status substantially increased the risk of peptic ulcer bleeding in patients on non-aspirin antiplatelet agents (OR = 4.37, 95% CI = 1.28-14.99), concomitant aspirin/nonsteroidal anti-inflammatory drug intake (OR = 5.85, 95% CI = 1.68-20.36) and combined antiplatelet therapy (OR = 8.43, 95% CI = 1.09-65.17). After further adjustment for proton pump inhibitor intake, H. pylori infection was still a risk factor for peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users. Helicobacter pylori infection increases the risk of peptic ulcer bleeding in peptic ulcer disease patients on nonsteroidal anti-inflammatory drugs, aspirin and non

[Combination drug therapy in leprosy].

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Terencio de las Aguas, J

1983-01-01

The importance of polichemotherapy in multibacilar leprosy (LL and LD) in patients without any previous therapy as in those diagnosticated and under monotherapy most of all in the resistance patients is presented. Sulphones, clofazimine and rifampicine are selected as first rate drugs and protionamide-etionamide as second rate drugs. The therapy plans with the association of two and three drugs and the convenience of continuing indefinitely with at least one of the drugs are presented insisting on the advantages of the clofazimine-sulphones and rifampicine-sulphones associations. The necessity of immunotherapy for recover of celular immunity against the bacilus, is the only form of preventing relapses and drug resistance.

[Non steroidal anti-inflammatory drugs and rheumatic diseases].

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Cossermelli, W; Pastor, E H

1995-01-01

Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of medicaments that reduced the symptoms of inflamation in rheumatic disease. This article emphasizes similarities and class characteristics of the NSAID, mechanisms of action, and drug-interactions.

Blockade of Tumor Necrosis Factor-Alpha: A Role for Adalimumab in Neovascular Age-Related Macular Degeneration Refractory to Anti-Angiogenesis Therapy

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Beatriz Fernández-Vega

2016-03-01

Full Text Available Aims: To report a case of wet age-related macular degeneration (wet-AMD refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF therapy in a patient who showed visual and anatomical improvement and stabilization after starting a subcutaneous treatment course with adalimumab, an anti-tumor necrosis factor-alpha (TNF-α drug, for concomitant Crohn's disease. Methods: Observational case report of a female patient. Ophthalmological evaluation was performed by slit lamp and ophthalmoscopy (posterior pole and anterior segment. Best-corrected visual acuity (BCVA was determined, and imaging was performed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT. Intravitreal therapies used and treatment with anti-TNF-α were recorded. Results: A 64-year-old woman with wet-AMD was treated with fourteen intravitreal injections of ranibizumab (0.5 mg for a period of 40 months with intervals of 1-6 months. She initially showed a good visual and anatomical response to periodic anti-VEGF treatment but during check visits, anatomical and functional responses deteriorated. At the 40-month follow-up, the patient had developed Crohn's disease, and her rheumatologist started treatment with adalimumab (40 mg subcutaneously every 2 weeks. During the 25 months of treatment with adalimumab, the patient did not require any additional intravitreal anti-VEGF treatments because her BCVA, clinical, and OCT findings improved and remained stable. Conclusions: We described a case of a patient with wet-AMD refractory to anti-VEGF therapy, which clinically benefited from subcutaneous adalimumab therapy. Treatment with subcutaneous anti-TNF-α in combination with anti-VEGF therapy avoids the high cost and risks related to multiple intravitreal anti-VEGF injections with good functional and anatomic outcomes.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

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Jat, Kana R; Walia, Dinesh K; Khairwa, Anju

2018-03-18

Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018. Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. Only one

Drug interactions between common illicit drugs and prescription therapies.

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Lindsey, Wesley T; Stewart, David; Childress, Darrell

2012-07-01

The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4-methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drug-drug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.

Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration

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Tai-Chi Lin

2015-11-01

Full Text Available Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration.

Synergistic gene and drug tumor therapy using a chimeric peptide.

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Han, Kai; Chen, Si; Chen, Wei-Hai; Lei, Qi; Liu, Yun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2013-06-01

Co-delivery of gene and drug for synergistic therapy has provided a promising strategy to cure devastating diseases. Here, an amphiphilic chimeric peptide (Fmoc)2KH7-TAT with pH-responsibility for gene and drug delivery was designed and fabricated. As a drug carrier, the micelles self-assembled from the peptide exhibited a much faster doxorubicin (DOX) release rate at pH 5.0 than that at pH 7.4. As a non-viral gene vector, (Fmoc)(2)KH(7)-TAT peptide could satisfactorily mediate transfection of pGL-3 reporter plasmid with or without the existence of serum in both 293T and HeLa cell-lines. Besides, the endosome escape capability of peptide/DNA complexes was investigated by confocal laser scanning microscopy (CLSM). To evaluate the co-delivery efficiency and the synergistic anti-tumor effect of gene and drug, p53 plasmid and DOX were simultaneously loaded in the peptide micelles to form micelleplexes during the self-assembly of the peptide. Cellular uptake and intracellular delivery of gene and drug were studied by CLSM and flow cytometry respectively. And p53 protein expression was determined via Western blot analysis. The in vitro cytotoxicity and in vivo tumor inhibition effect were also studied. Results suggest that the co-delivery of gene and drug from peptide micelles resulted in effective cell growth inhibition in vitro and significant tumor growth restraining in vivo. The chimeric peptide-based gene and drug co-delivery system will find great potential for tumor therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Anti-obesity drugs: past, present and future

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R. John Rodgers

2012-09-01

Full Text Available The ideal anti-obesity drug would produce sustained weight loss with minimal side effects. The mechanisms that regulate energy balance have substantial built-in redundancy, overlap considerably with other physiological functions, and are influenced by social, hedonic and psychological factors that limit the effectiveness of pharmacological interventions. It is therefore unsurprising that anti-obesity drug discovery programmes have been littered with false starts, failures in clinical development, and withdrawals due to adverse effects that were not fully appreciated at the time of launch. Drugs that target pathways in metabolic tissues, such as adipocytes, liver and skeletal muscle, have shown potential in preclinical studies but none has yet reached clinical development. Recent improvements in the understanding of peptidergic signalling of hunger and satiety from the gastrointestinal tract mediated by ghrelin, cholecystokinin (CCK, peptide YY (PYY and glucagon-like peptide-1 (GLP-1, and of homeostatic mechanisms related to leptin and its upstream pathways in the hypothalamus, have opened up new possibilities. Although some have now reached clinical development, it is uncertain whether they will meet the strict regulatory hurdles required for licensing of an anti-obesity drug. However, GLP-1 receptor agonists have already succeeded in diabetes treatment and, owing to their attractive body-weight-lowering effects in humans, will perhaps also pave the way for other anti-obesity agents. To succeed in developing drugs that control body weight to the extent seen following surgical intervention, it seems obvious that a new paradigm is needed. In other therapeutic arenas, such as diabetes and hypertension, lower doses of multiple agents targeting different pathways often yield better results than strategies that modify one pathway alone. Some combination approaches using peptides and small molecules have now reached clinical trials, although recent

Emerging Technologies and Generic Assays for the Detection of Anti-Drug Antibodies

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Michael A. Partridge

2016-01-01

Full Text Available Anti-drug antibodies induced by biologic therapeutics often impact drug pharmacokinetics, pharmacodynamics response, clinical efficacy, and patient safety. It is critical to assess the immunogenicity risk of potential biotherapeutics in producing neutralizing and nonneutralizing anti-drug antibodies, especially in clinical phases of drug development. Different assay methodologies have been used to detect all anti-drug antibodies, including ELISA, radioimmunoassay, surface plasmon resonance, and electrochemiluminescence-based technologies. The most commonly used method is a bridging assay, performed in an ELISA or on the Meso Scale Discovery platform. In this report, we aim to review the emerging new assay technologies that can complement or address challenges associated with the bridging assay format in screening and confirmation of ADAs. We also summarize generic anti-drug antibody assays that do not require drug-specific reagents for nonclinical studies. These generic assays significantly reduce assay development efforts and, therefore, shorten the assay readiness timeline.

Various anti-motion sickness drugs and core body temperature changes.

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Cheung, Bob; Nakashima, Ann M; Hofer, Kevin D

2011-04-01

Blood flow changes and inactivity associated with motion sickness appear to exacerbate the rate of core temperature decrease during subsequent body cooling. We investigated the effects of various classes of anti-motion sickness drugs on core temperature changes. There were 12 healthy male and female subjects (20-35 yr old) who were given selected classes of anti-motion sickness drugs prior to vestibular Coriolis cross coupling induced by graded yaw rotation and periodic pitch-forward head movements in the sagittal plane. All subjects were then immersed in water at 18 degrees C for a maximum of 90 min or until their core temperature reached 35 degrees C. Double-blind randomized trials were administered, including a placebo, a non-immersion control with no drug, and six anti-motion sickness drugs: meclizine, dimenhydrinate, chlorpheniramine, promethazine + dexamphetamine, promethazine + caffeine, and scopolamine + dexamphetamine. A 7-d washout period was observed between trials. Core temperature and the severity of sickness were monitored throughout each trial. A repeated measures design was performed on the severity of sickness and core temperature changes prior to motion provocation, immediately after the motion sickness end point, and throughout the period of cold-water immersion. The most effective anti-motion sickness drugs, promethazine + dexamphetamine (with a sickness score/duration of 0.65 +/- 0.17) and scopolamine + dexamphetamine (with a sickness score/duration of 0.79 +/- 0.17), significantly attenuated the decrease in core temperature. The effect of this attenuation was lower in less effective drugs. Our results suggest that the two most effective anti-motion sickness drugs are also the most effective in attenuating the rate of core temperature decrease.

Drug therapy of leprosy

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A. A. Kubanov

2016-01-01

Full Text Available Leprosy (Hansen’s disease is a chronic granulomatous bacterial infection mainly affecting the skin and peripheral nervous system yet also involving other organs and systems as a result of a pathological process. The causative agent of leprosy - Mycobacterium leprae - is an obligate intracellular microorganism. Despite the removal of a threat of a leprosy epidemic, European countries still record outbreaks of the disease mainly among migrants coming from endemic areas. A golden standard of the treatment of leprosy is a WHO-recommended combined drug therapy comprising drugs such as dapsone, clofazimine and rifampicin. The article provides current data on the mechanisms of action, efficacy and safety of these drugs and their combined scheme of treatment obtained as a result of clinical trials. Moreover, it also reviews new regimens of the drug therapy of leprosy including those with the use of drugs from the group of fluoroquinols as well as immunotherapy of the disease.

Factors influencing anti-asthmatic generic drug consumption in Morocco: 1999-2010.

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Ghanname, Imane; Ahid, Samir; Berrada, Ghizlane; Belaiche, Abdelmjid; Hassar, Mohammed; Cherrah, Yahia

2014-01-01

The increasing availability of generic drugs (GD) resulted in a remarkable reduction in treatment costs that allowed a better access to health care.The aim of this study is to evaluate the share of anti-asthmatic generic drugs during the period 1999-2010 in Morocco and to look at the factors influencing generic development. In this study, we used Moroccan sales data from IMS Health (Intercontinental Marketing Services). The consumption of the drugs was expressed in DDD/1000 inhabitants/day according to the WHO ATC/DDD methodology. Between 1999 and 2010, anti-asthmatic consumption increased from 3.91 to 14.43 DDD/1000 inhabitants/day. The market of anti-asthmatic generic drugs progressed from 1.83 (47%) to 2.18 (23%) DDD/1000 inhabitants/day from 1999 to 2010. In 2010, inhaled glucocorticosteroids ranked first (0.83 DDD/1000 inhabitants/day), followed by inhaled short acting beta agonists (0.73 DDD/1000 inhabitants/day). The number of brands went from 27 in 1999 to 34 in 2010, with a generic share increasing from 55.55% to 70.59%. The number of anti-asthmatic pharmaceutical preparations increased from 57 to 64 during the same period, of which 31 and 42 were generic preparations. In 2010, the total cost of anti-asthmatic dugs was about 22 million euro, the generics representing 14 million euro. Despite the introduction of a compulsory insurance scheme called "AMO", that allows a refund for 69.5% of anti-asthmatic specialties marketed in Morocco, anti-asthmatic generic drug consumption remains limited. The Moroccan market is still largely dominated by the originator drugs with still valid patents.

Effectiveness and Safety of Immunomodulators With Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

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Osterman, Mark T; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R; Lewis, James D

2015-07-01

The benefit of continuing immunomodulators when "stepping up" to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness-surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery-and 2 metrics of safety-serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as "step up" after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73-1.96), hospitalization (HR, 0.82; 0.57-1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88-1.34), and serious infection (HR, 0.93; 0.88-1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21-5.73) and herpes zoster (HR, 3.16; 1.25-7.97) were increased with combination therapy. We found that continuation of immunomodulators after "stepping up" to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

[Cyclooxygenase inhibitors and antiplatelet effect of acetylsalicylic acid. selective approach to nonsteroidal anti-inflammatory drugs in cardiological practice].

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Lomakin, N V; Gruzdev, A K

2011-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent class of medicines which is wide concerning chemical structure and mechanism of action. In the light of contradictory data on efficacy and safety of NSAID in cardiovascular patients selection of most appropriate NSAID (basing on profile of efficacy and safety) in patients receiving continuous therapy with low dose aspirin appears to be a problem. In this paper we discuss peculiarities of drug interaction between cyclooxygenase inhibitors and acetylsalicylic acid, and principles of selection of adequate NSAI.

Proteomics of anti-cancer drugs

Czech Academy of Sciences Publication Activity Database

Kovářová, Hana; Martinková, Jiřina; Hrabáková, Rita; Skalníková, Helena; Novák, Petr; Hajdůch, M.; Gadher, S. J.

2009-01-01

Roč. 276, Supplement 1 (2009), s. 84-84 E-ISSN 1742-4658. [34th FEBS Congress. 04.07.2009-09.07.2009, Praha] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : proteomics * anti-cancer drugs * biomarkers Subject RIV: FD - Oncology ; Hematology

Bio markers and Anti-EGFR therapies for Krads wild-type tumors in metastatic colorectal cancer patients; Biomarcadores y terapeutica ANTI-EGFR en el cancer colorrectal metastasico en pacientes con K-Ras no mutado

Energy Technology Data Exchange (ETDEWEB)

Diaz Rubio Garcia, E

2009-07-01

The natural history of metastasis colorectal cancer has being clearly modified in terms of response rate, time to progression and overall survival, once the anti-EGFR monoclonal antibodies (cetuximab and panitumumab) have emerged in combination with the standard cytotoxic chemotherapy (FOLFOX and FOLFIRI). However, the benefit from cetuximab and panitumumab is only confined to KRAS-wild type (KRAS-wt) colorectal tumors, while KRAS mutated tumors do not respond to these drugs. The 65 % of colorectal tumors are KRAS-wt tumors, but efficacy of antiEGFR therapies is detected only in 60-70 % of these KRAS-wt tumors. Other biomarkers and molecular pathways must be involved in the response of the antiEGFR therapies for the KRAS-wt colorectal tumors, such as the EGFR ligands, the EGFR-phosphorilated levels, the number of EGFR copies, the status of the KRAS effected B-RAF and the alternative intracellular signaling pathways PIK3CA/PTEN/AKT and JAK/STAT. A battery of these biomarkers is needed to select the most sensitive patients to the antiEGFR therapies. This pattern may represent a novel favorable cost-effectiveness tool to develop tailored treatments. A review of these biomarkers and molecular pathways, involved in the antiEGFR therapies response, is performed. (Author) 68 refs.

Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

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Arun K. Nalla

2016-03-01

Full Text Available Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC. Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.

Targeted delivery of anti-tuberculosis drugs to macrophages: targeting mannose receptors

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Filatova, L. Yu; Klyachko, N. L.; Kudryashova, E. V.

2018-04-01

The development of systems for targeted delivery of anti-tuberculosis drugs is a challenge of modern biotechnology. Currently, these drugs are encapsulated in a variety of carriers such as liposomes, polymers, emulsions and so on. Despite successful in vitro testing of these systems, virtually no success was achieved in vivo, because of low accessibility of the foci of infection located in alveolar macrophage cells. A promising strategy for increasing the efficiency of therapeutic action of anti-tuberculosis drugs is to encapsulate the agents into mannosylated carriers targeting the mannose receptors of alveolar macrophages. The review addresses the methods for modification of drug substance carriers, such as liposomes and biodegradable polymers, with mannose residues. The use of mannosylated carriers to deliver anti-tuberculosis agents increases the drug circulation time in the blood stream and increases the drug concentration in alveolar macrophage cells. The bibliography includes 113 references.

Diagnostic and therapeutic progress of multi-drug resistance with anti-HBV nucleos(t)ide analogues

Institute of Scientific and Technical Information of China (English)

Zhuo-Lun Song; Yu-Jun Cui; Wei-Ping Zheng; Da-Hong Teng; Hong Zheng

2012-01-01

Nucleos(t)ide analogues (NA) are a breakthrough in the treatment and management of chronic hepatitis B.NA could suppress the replication of hepatitis B virus (HBV) and control the progression of the disease.However,drug resistance caused by their long-term use becomes a practical problem,which influences the long-term outcomes in patients.Liver transplantation is the only choice for patients with HBV-related end-stage liver disease.But,the recurrence of HBV after transplantation often caused by the development of drug resistance leads to unfavorable outcomes for the recipients.Recentiy,the multi-drug resistance (MDR) has become a common issue raised due to the development and clinical application of a variety of NA.This may complicate the antiviral therapy and bring poorly prognostic outcomes.Although clinical evidence has suggested that combination therapy with different NA could effectively reduce the viral load in patients with MDR,the advent of new antiviral agents with high potency and high genetic barrier to resistance brings hope to antiviral therapy.The future of HBV researches relies on how to prevent the MDR occurrence and develop reasonable and effective treatment strategies.This review focuses on the diagnostic and therapeutic progress in MDR caused by the anti-HBV NA and describes some new research progress in this field.

A screen to identify drug resistant variants to target-directed anti-cancer agents

Directory of Open Access Journals (Sweden)

Azam Mohammad

2003-01-01

Full Text Available The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec, a specific inhibitor of the Chronic Myeloid Leukemia (CML-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair.

Antiretroviral therapy: current drugs.

Science.gov (United States)

Pau, Alice K; George, Jomy M

2014-09-01

The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

Imaging biomarkers in Parkinson?s disease and Parkinsonian syndromes: current and emerging concepts

OpenAIRE

Saeed, Usman; Compagnone, Jordana; Aviv, Richard I.; Strafella, Antonio P.; Black, Sandra E.; Lang, Anthony E.; Masellis, Mario

2017-01-01

Two centuries ago in 1817, James Parkinson provided the first medical description of Parkinson?s disease, later refined by Jean-Martin Charcot in the mid-to-late 19th century to include the atypical parkinsonian variants (also termed, Parkinson-plus syndromes). Today, Parkinson?s disease represents the second most common neurodegenerative disorder with an estimated global prevalence of over 10 million. Conversely, atypical parkinsonian syndromes encompass a group of relatively heterogeneous d...

The Effects of First-Line Anti-Tuberculosis Drugs on the Actions of Vitamin D in Human Macrophages.

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Chesdachai, Supavit; Zughaier, Susu M; Hao, Li; Kempker, Russell R; Blumberg, Henry M; Ziegler, Thomas R; Tangpricha, Vin

2016-12-01

Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance is uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1N1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH) 2 D 3 strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease of hCAP18 mRNA at the dosage of 10 ug/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D 3 (1.2 million IU over 8 weeks, n=13) versus placebo (n=18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18.These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages.

Interaction between anti-hypertensive and non-steroidal anti ...

African Journals Online (AJOL)

AKS Publication

Department of Physiotherapy, College of Medicine, University College Hospital,. University of Ibadan, Nigeria. (Received 19 ... that NSAIDs diminish the effects of anti-hypertensive drugs and may lead to an ineffective hypertension therapy. ..... repair, regeneration and transplantation. Instr Course Lect. 1998;47:487-504. 15.

Non-steroidal anti-inflammatory drug use and the risk of Parkinson's disease

DEFF Research Database (Denmark)

Manthripragada, Angelika D; Schernhammer, Eva S; Qiu, Jiaheng

2011-01-01

Experimental evidence supports a preventative role for non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson's disease (PD).......Experimental evidence supports a preventative role for non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson's disease (PD)....

Long-term results of repeated anti-vascular endothelial growth factor therapy in eyes with retinal pigment epithelial tears.

Science.gov (United States)

Moreira, Carlos A; Arana, Luis A; Zago, Rommel J

2013-02-01

To evaluate the long-term results of retinal pigment epithelium tears in eyes treated with repeated anti-vascular endothelial growth factor (VEGF) therapy. Five patients with retinal pigment epithelial tears (without foveal center involvement) after anti-VEGF injection were studied retrospectively. Mean follow-up time was 52 months, with measurements of visual acuity and evaluation of macular findings by angiography and optical coherence tomography during this period. All eyes had a persistent submacular neovascular membrane 30 days after the tear. An anti-VEGF drug was reinjected until the membranes stopped leaking. The mean initial visual acuity immediately after the tear was 20/160, and the mean final visual acuity was 20/60. The number of anti-VEGF reinjections varied from two to eight during the follow-up period. Long-term optical coherence tomography analysis showed reduced fluid and remodeling of the torn retinal pigment epithelium. Long-term visual results with repeated anti-VEGF therapy are not as devastating as suggested previously. Visual acuity and metamorphopsia improve with time as long as the neovascular membrane is inactive. Optical coherence tomography changes in the macular area reflect the visual acuity improvement.

Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy

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Laura Pisarsky

2016-05-01

Full Text Available Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. Here, we demonstrate potent anti-angiogenic efficacy of the multi-kinase inhibitors nintedanib and sunitinib in a mouse model of breast cancer. However, after an initial regression, tumors resume growth in the absence of active tumor angiogenesis. Gene expression profiling of tumor cells reveals metabolic reprogramming toward anaerobic glycolysis. Indeed, combinatorial treatment with a glycolysis inhibitor (3PO efficiently inhibits tumor growth. Moreover, tumors establish metabolic symbiosis, illustrated by the differential expression of MCT1 and MCT4, monocarboxylate transporters active in lactate exchange in glycolytic tumors. Accordingly, genetic ablation of MCT4 expression overcomes adaptive resistance against anti-angiogenic therapy. Hence, targeting metabolic symbiosis may be an attractive avenue to avoid resistance development to anti-angiogenic therapy in patients.

Novel High-Throughput Drug Screening Platform for Chemotherapy-Induced Axonal Neuropathy

Science.gov (United States)

2014-05-01

from anti-cancer drug therapy [1,2]. Platinum drugs, taxanes, proteasome inhibitors, vinca alkaloids, epothilones, and immunomodulators are the...and immunomodulators are the standard of anti-cancer therapies for the six most cancers. An estimated 2010 incidence of 994, 680 cases for these

The prevention of gastropathy and upper abdominal symptoms caused by nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Vakil, Nimish

2006-01-01

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is increasing, primarily due to arthritis in the aging population. This article reviews current data on the risk of gastrointestinal complications related to NSAIDs and strategies to manage risk in patients taking these agents. Risks of NSAID use include gastrointestinal ulceration, hemorrhage, or perforation; renal dysfunction; death; and dyspepsia. Alternate therapies include use of non-NSAID analgesics; low-dose NSAIDs; and concurrent administration of cytoprotective agents with NSAIDs, acid inhibitors, proton pump inhibitors, and COX-2 agents.

Patient Affected by Beta-Propeller Protein-Associated Neurodegeneration: A Therapeutic Attempt with Iron Chelation Therapy

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Mattia Fonderico

2017-08-01

Full Text Available Here, we report the case of a 36-year-old patient with a diagnosis of de novo mutation of the WDR45 gene, responsible for beta-propeller protein-associated neurodegeneration, a phenotypically distinct, X-linked dominant form of Neurodegeneration with Brain Iron Accumulation. The clinical history is characterized by a relatively stable intellectual disability and a hypo-bradykinetic and hypertonic syndrome with juvenile onset. Genetic investigations and T1 and T2-weighted MR images align with what is described in literature. The patient was also subjected to PET with 18-FDG investigation and DaT-Scan study. In reporting relevant clinical data, we want to emphasize the fact that the patient received a chelation therapy with deferiprone (treatment already used in other forms of NBIA with encouraging results, which, however, had to be interrupted because the parkinsonian symptoms worsened. Conversely, the patient has benefited from non-drug therapies and, in particular, from an adapted motor activity with assisted pedaling (method in the process of validation in treatments of parkinsonian syndromes, which started before the treatment with deferiprone and still continues.

Self-Assembled Nanocarriers Based on Amphiphilic Natural Polymers for Anti- Cancer Drug Delivery Applications.

Science.gov (United States)

Sabra, Sally; Abdelmoneem, Mona; Abdelwakil, Mahmoud; Mabrouk, Moustafa Taha; Anwar, Doaa; Mohamed, Rania; Khattab, Sherine; Bekhit, Adnan; Elkhodairy, Kadria; Freag, May; Elzoghby, Ahmed

2017-01-01

Micellization provides numerous merits for the delivery of water insoluble anti-cancer therapeutic agents including a nanosized 'core-shell' drug delivery system. Recently, hydrophobically-modified polysaccharides and proteins are attracting much attention as micelle forming polymers to entrap poorly soluble anti-cancer drugs. By virtue of their small size, the self-assembled micelles can passively target tumor tissues via enhanced permeation and retention effect (EPR). Moreover, the amphiphilic micelles can be exploited for active-targeted drug delivery by attaching specific targeting ligands to the outer micellar hydrophilic surface. Here, we review the conjugation techniques, drug loading methods, physicochemical characteristics of the most important amphiphilic polysaccharides and proteins used as anti-cancer drug delivery systems. Attention focuses on the mechanisms of tumor-targeting and enhanced anti-tumor efficacy of the encapsulated drugs. This review will highlight the remarkable advances of hydrophobized polysaccharide and protein micelles and their potential applications as anti-cancer drug delivery nanosystems. Micellar nanocarriers fabricated from amphiphilic natural polymers hold great promise as vehicles for anti-cancer drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Neuroprotective and behavioral efficacy of intravenous transplanted adipose stem cells in experimental Parkinsonian rat models

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Malihe Nakhaeifard

2016-02-01

Full Text Available Background: Parkinson's disease is a deficiency of dopamine in the striatum, characterized by bradykinesis, rigidity and resting tremor. Adipose tissue-Derived Stem Cells (ADSCs have many advantages for cell therapy because of the easy availability and pluripotency without ethical problems. In this research, the effects of ADSCs transplantation on motor impairment of rat Parkinsonian models were evaluated. Materials and Methods: Parkinson model was constructed by the unilateral lesion of striatum of male Wistar rats using 20µg of 6-hydroxydopamine (6-OHDA as lesion group. Cell and α-MEM (α-minimal essential medium groups were lesioned animals that received intravenous injection of 3×106 cells suspended in medium and medium repectively. All rats were evaluated behaviorally with rotarod and apomorphine-induced rotation tests, at 4 and 8 weeks after cell transplantation. Results: Lesion and α-MEM groups showed increased contralateral turns while cell group significantly ameliorated both in rotarod and apomorphine-induced rotation tests. There was a significant difference of contralateral turns between cell and lesioned groups at 8 weeks after transplantation. Lesioned rats showed significant decrease of staying on the rod as compared to control, but in cell group there was a significant increase in comparision with the lesioned animals. Conclusion: ADSCs injected intravenously promote functional recovery in Parkinsonian rats.

Parkinsonian phenotype in Machado-Joseph disease (MJD/SCA3: a two-case report

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Vasconcelos João

2011-10-01

Full Text Available Abstract Background Machado-Joseph disease (MJD, or spinocerebellar ataxia type 3 (SCA3, is an autosomal dominant neurodegenerative disorder of late onset, which is caused by a CAG repeat expansion in the coding region of the ATXN3 gene. This disease presents clinical heterogeneity, which cannot be completely explained by the size of the repeat tract. MJD presents extrapyramidal motor signs, namely Parkinsonism, more frequently than the other subtypes of autosomal dominant cerebellar ataxias. Although Parkinsonism seems to segregate within MJD families, only a few MJD patients develop parkinsonian features and, therefore, the clinical and genetic aspects of these rare presentations remain poorly investigated. The main goal of this work was to describe two MJD patients displaying the parkinsonian triad (tremor, bradykinesia and rigidity, namely on what concerns genetic variation in Parkinson's disease (PD associated loci (PARK2, LRRK2, PINK1, DJ-1, SNCA, MAPT, APOE, and mtDNA tRNAGln T4336C. Case presentation Patient 1 is a 40 year-old female (onset at 30 years of age, initially with a pure parkinsonian phenotype (similar to the phenotype previously reported for her mother. Patient 2 is a 38 year-old male (onset at 33 years of age, presenting an ataxic phenotype with parkinsonian features (not seen either in other affected siblings or in his father. Both patients presented an expanded ATXN3 allele with 72 CAG repeats. No PD mutations were found in the analyzed loci. However, allelic variants previously associated with PD were observed in DJ-1 and APOE genes, for both patients. Conclusions The present report adds clinical and genetic information on this particular and rare MJD presentation, and raises the hypothesis that DJ-1 and APOE polymorphisms may confer susceptibility to the parkinsonian phenotype in MJD.

Anti-influenza drugs: the development of sialidase inhibitors.

Science.gov (United States)

von Itzstein, Mark; Thomson, Robin

2009-01-01

Viruses, particularly those that are harmful to humans, are the 'silent terrorists' of the twenty-first century. Well over four million humans die per annum as a result of viral infections alone. The scourge of influenza virus has plagued mankind throughout the ages. The fact that new viral strains emerge on a regular basis, particularly out of Asia, establishes a continual socio-economic threat to mankind. The arrival of the highly pathogenic avian influenza H5N1 heightened the threat of a potential human pandemic to the point where many countries have put in place 'preparedness plans' to defend against such an outcome. The discovery of the first designer influenza virus sialidase inhibitor and anti-influenza drug Relenza, and subsequently Tamiflu, has now inspired a number of continuing efforts towards the discovery of next generation anti-influenza drugs. Such drugs may act as 'first-line-of-defence' against the spread of influenza infection and buy time for necessary vaccine development particularly in a human pandemic setting. Furthermore, the fact that influenza virus can develop resistance to therapeutics makes these continuing efforts extremely important. An overview of the role of the virus-associated glycoprotein sialidase (neuraminidase) and some of the most recent developments towards the discovery of anti-influenza drugs based on the inhibition of influenza virus sialidase is provided in this chapter.

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

Science.gov (United States)

Yeo, Chien Ing; Ooi, Kah Kooi; Tiekink, Edward R T

2018-06-11

A new era of metal-based drugs started in the 1960s, heralded by the discovery of potent platinum-based complexes, commencing with cisplatin [(H₃N)₂PtCl₂], which are effective anti-cancer chemotherapeutic drugs. While clinical applications of gold-based drugs largely relate to the treatment of rheumatoid arthritis, attention has turned to the investigation of the efficacy of gold(I) and gold(III) compounds for anti-cancer applications. This review article provides an account of the latest research conducted during the last decade or so on the development of gold compounds and their potential activities against several cancers as well as a summary of possible mechanisms of action/biological targets. The promising activities and increasing knowledge of gold-based drug metabolism ensures that continued efforts will be made to develop gold-based anti-cancer agents.

Drug therapy in headache.

Science.gov (United States)

Weatherall, Mark W

2015-06-01

All physicians will encounter patients with headaches. Primary headache disorders are common, and often disabling. This paper reviews the principles of drug therapy in headache in adults, focusing on the three commonest disorders presenting in both primary and secondary care: tension-type headache, migraine and cluster headache. The clinical evidence on the basis of which choices can be made between the currently available drug therapies for acute and preventive treatment of these disorders is presented, and information given on the options available for the emergency parenteral treatment of refractory migraine attacks and cluster headache. © Royal College of Physicians 2015. All rights reserved.

Associations between quantitative mobility measures derived from components of conventional mobility testing and Parkinsonian gait in older adults.

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Aron S Buchman

Full Text Available OBJECTIVE: To provide objective measures which characterize mobility in older adults assessed in the community setting and to examine the extent to which these measures are associated with parkinsonian gait. METHODS: During conventional mobility testing in the community-setting, 351 ambulatory non-demented Memory and Aging Project participants wore a belt with a whole body sensor that recorded both acceleration and angular velocity in 3 directions. We used measures derived from these recordings to quantify 5 subtasks including a walking, b transition from sit to stand, c transition from stand to sit, d turning and e standing posture. Parkinsonian gait and other mild parkinsonian signs were assessed with a modified version of the original Unified Parkinson's Disease Rating Scale (mUPDRS. RESULTS: In a series of separate regression models which adjusted for age and sex, all 5 mobility subtask measures were associated with parkinsonian gait and accounted for 2% to 32% of its variance. When all 5 subtask measures were considered in a single model, backward elimination showed that measures of walking sit to stand and turning showed independent associations with parkinsonian gait and together accounted for more than 35% of its variance. Cross-validation using data from a 2(nd group of 258 older adults showed similar results. In similar analyses, only walking was associated with bradykinesia and sway with tremor. INTERPRETATION: Quantitative mobility subtask measures vary in their associations with parkinsonian gait scores and other parkinsonian signs in older adults. Quantifying the different facets of mobility has the potential to facilitate the clinical characterization and understanding the biologic basis for impaired mobility in older adults.

Associations between Quantitative Mobility Measures Derived from Components of Conventional Mobility Testing and Parkinsonian Gait in Older Adults

Science.gov (United States)

Buchman, Aron S.; Leurgans, Sue E.; Weiss, Aner; VanderHorst, Veronique; Mirelman, Anat; Dawe, Robert; Barnes, Lisa L.; Wilson, Robert S.; Hausdorff, Jeffrey M.; Bennett, David A.

2014-01-01

Objective To provide objective measures which characterize mobility in older adults assessed in the community setting and to examine the extent to which these measures are associated with parkinsonian gait. Methods During conventional mobility testing in the community-setting, 351 ambulatory non-demented Memory and Aging Project participants wore a belt with a whole body sensor that recorded both acceleration and angular velocity in 3 directions. We used measures derived from these recordings to quantify 5 subtasks including a) walking, b) transition from sit to stand, c) transition from stand to sit, d) turning and e) standing posture. Parkinsonian gait and other mild parkinsonian signs were assessed with a modified version of the original Unified Parkinson’s Disease Rating Scale (mUPDRS). Results In a series of separate regression models which adjusted for age and sex, all 5 mobility subtask measures were associated with parkinsonian gait and accounted for 2% to 32% of its variance. When all 5 subtask measures were considered in a single model, backward elimination showed that measures of walking sit to stand and turning showed independent associations with parkinsonian gait and together accounted for more than 35% of its variance. Cross-validation using data from a 2nd group of 258 older adults showed similar results. In similar analyses, only walking was associated with bradykinesia and sway with tremor. Interpretation Quantitative mobility subtask measures vary in their associations with parkinsonian gait scores and other parkinsonian signs in older adults. Quantifying the different facets of mobility has the potential to facilitate the clinical characterization and understanding the biologic basis for impaired mobility in older adults. PMID:24465997

Drug delivery system and radiation therapy

International Nuclear Information System (INIS)

Shibata, Tokushi

2005-01-01

This paper describes the review of radiation therapy, neutron capture therapy (NCT) and drug delivery system for the latter. In cancer radiation therapy, there are problems of body movement like breathing, needless irradiation of normal tissues, difficulty to decide the correct irradiation position and tumor morphology. NCT has advantages to overcome these, and since boron has a big cross section for thermal neutron, NPT uses the reaction 10 B(n, α) 7 Li in the target cancer which previously incorporated the boron-containing drug. During the period 1966-1996, 246 patients were treated with this in Japan and the treatment has been continued thereafter. The tasks for NCT are developments of drug delivery system efficient to deliver the drug into the tumor and of convenient neutron source like the accelerator. (S.I.)

Behaviour therapy for obesity treatment considering approved drug therapy

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Wasem, Jürgen

2008-05-01

Full Text Available Introduction: Obesity is a worldwide health problem whose prevalence is on the increase. Many obesity-associated diseases require intensive medical treatment and are the cause of a large proportion of health-related expenditures in Germany. Treatment of obesity includes nutritional, exercise and behaviour therapy, usually in combination. The goal of behaviour therapy for obesity is to bring about a long-term alteration in the eating and exercise habits of overweight and obese individuals. Under certain circumstances, drug treatment may be indicated. Objectives: What is the effectiveness of behaviour therapy for obesity considering approved drugs reduce weight under medical, economic, ethical-social and legal aspects? Methods: A systematic review was conducted using relevant electronic literature databases. Publications chosen according to predefined criteria are evaluated by approved methodical standards of the evidence-based medicine systematically and qualitatively. Results: In total 18 studies, included one HTA and one meta-analysis could be identified according to the predefined inclusion criteria. Three studies compare behaviour therapy to other therapy forms (advice or instruction on nutritional changes, physical activity or a combination of the two, six studies evaluate different forms of behaviour therapy, four studies and four studies compare behaviour therapies mediated by Internet or telephone. Three studies could be identified examining the effect of the combination of behaviour and drug therapy. Furthermore one HTA and one meta-analysis could be included in the evaluation. The behaviour therapy in comparison with other therapy forms reveals a higher effectiveness. In comparison of the different therapeutic approaches of the behaviour therapy intensive behaviour therapy forms and group therapy show a higher effectiveness. Studies related to behaviour therapy based on media support demonstrate a weight reduction both through the

Renal function in healthy dogs therapy with anti-inflammatory drugs

OpenAIRE

Borges, Marina

2011-01-01

Os anti-inflamatórios não-esteroidais têm uso extremamente difundido na clínica de pequenos animais, devido às suas propriedades analgésicas e anti-inflamatórias. Entretanto, o uso desses fármacos pode produzir alterações da função renal. O presente estudo teve como objetivo avaliar a função renal de cães saudáveis, submetidos à terapia com anti-inflamatórios não-esteroidais não seletivos, COX-2 preferenciais e COX-2 seletivos. Foram utilizados 30 cães, sem raça definida, adultos, machos e fê...

Adherence to anti-retroviral drugs in pregnant and lactating HIV ...

African Journals Online (AJOL)

Background: Anti-retroviral drugs reduce morbidity and mortality due to HIV and prevent transmission from mother to child. But compliance on anti-retroviral treatment is an essential element for the success of therapeutic goals. Objective: To assess the level of compliance of anti-retroviral treatment in pregnant and lactating ...

Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

Science.gov (United States)

Halasa, Salaheldin; Dickinson, Eva

2014-02-01

From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

National surveillance of Helicobacter pylori eradication therapy in Denmark. Results from registration of 34,582 prescriptions

DEFF Research Database (Denmark)

Juul, K.V.; Thomsen, V O; Nissen, A.

1998-01-01

cent of the patients had only one treatment course. In 16% of the eradication therapies, nonsteroid anti-inflammatory drugs had been prescribed within the previous 3 months, and 45% had an anti-ulcer drug prescribed 1-12 months after the H. pylori eradication therapy. Consumption of antibiotics used...... for H. pylori eradication accounted for 1.4% of the total consumption of antibiotics. CONCLUSIONS: The incidence of H. pylori eradication therapy was fairly stable but with changes in the pattern of drug regimens used. Anti-ulcer drugs were often given after H. pylori eradication therapy, suggesting...

Sensorimotor rhythm neurofeedback as adjunct therapy for Parkinson's disease.

Science.gov (United States)

Philippens, Ingrid H C H M; Wubben, Jacqueline A; Vanwersch, Raymond A P; Estevao, Dave L; Tass, Peter A

2017-08-01

Neurofeedback may enhance compensatory brain mechanisms. EEG-based sensorimotor rhythm neurofeedback training was suggested to be beneficial in Parkinson's disease. In a placebo-controlled study in parkinsonian nonhuman primates we here show that sensorimotor rhythm neurofeedback training reduces MPTP-induced parkinsonian symptoms and both ON and OFF scores during classical L-DOPA treatment. Our findings encourage further development of sensorimotor rhythm neurofeedback training as adjunct therapy for Parkinson's disease which might help reduce L-DOPA-induced side effects.

Anti-TNF-α biotherapies

DEFF Research Database (Denmark)

Bendtzen, Klaus

2012-01-01

This article discusses the rationale behind recommending immunopharmacological guidance of long-term therapies with genetically engineered anti-TNF-α immunoglobulin constructs. Arguments why therapeutic decision-making should not rely on clinical outcome alone are presented. Central...... to this is that the use of theranostics (i.e., monitoring circulating levels of functional anti-TNF-α drugs and antidrug antibodies) would markedly improve treatment because therapies can be tailored to individual patients and provide more effective and economical long-term therapies with minimal risk of side effects....... Large-scale immunopharmacological knowledge of how patients 'handle' TNF-α biopharmaceuticals would also help industry develop more effective and safer TNF-α inhibitors....

Anti-CD20 Cell Therapies in Multiple Sclerosis—A Fixed Dosing Schedule for Ocrelizumab is Overkill

Directory of Open Access Journals (Sweden)

Jagannadha Avasarala

2017-10-01

Full Text Available Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS. Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this—Why does the drug need to be dosed at fixed intervals and not based on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.

Subthalamic nucleus high-frequency stimulation restores altered electrophysiological properties of cortical neurons in parkinsonian rat.

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Bertrand Degos

Full Text Available Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.

Metastatic gastric cancer – focus on targeted therapies

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Meza-Junco J

2012-06-01

Full Text Available Judith Meza-Junco, Michael B SawyerDepartment of Oncology, Cross Cancer Institute, Edmonton, Alberta, CanadaAbstract: Gastric cancer (GC is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and signaling pathways is expected to improve GC therapy, and the integration of targeted therapies has recently become possible and appears to be promising. This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. Additionally, drugs that target angiogenesis pathways are also under investigation, particulary bevacizumab, ramucirumab, sorafenib, sunitinib, and cediranib. Other targeted agents in preclinical or early clinical development include mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors, anti-insulin-like growth factor, anti-heat shock proteins, and small molecules targeting Hedgehog signaling.Keywords: gastric cancer, targeted therapy, antiangiogenesis drugs, anti-EGFR drugs

Assessing the utility of an anti-malarial pharmacokinetic-pharmacodynamic model for aiding drug clinical development

Directory of Open Access Journals (Sweden)

Zaloumis Sophie

2012-08-01

Full Text Available Abstract Background Mechanistic within-host models relating blood anti-malarial drug concentrations with the parasite-time profile help in assessing dosing schedules and partner drugs for new anti-malarial treatments. A comprehensive simulation study to assess the utility of a stage-specific pharmacokinetic-pharmacodynamic (PK-PD model for predicting within-host parasite response was performed. Methods Three anti-malarial combination therapies were selected: artesunate-mefloquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine. The PK-PD model included parameters to represent the concentration-time profiles of both drugs, the initial parasite burden and distribution across the parasite life cycle, and the parasite multiplication factor due to asexual reproduction. The model also included the maximal killing rate of each drug, and the blood drug concentration associated with half of that killing effect (in vivo EC50, derived from the in vitro IC50, the extent of binding to 0.5% Albumax present in the in vitro testing media, and the drugs plasma protein binding and whole blood to plasma partitioning ratio. All stochastic simulations were performed using a Latin-Hypercube-Sampling approach. Results The simulations demonstrated that the proportion of patients cured was highly sensitive to the in vivo EC50 and the maximal killing rate of the partner drug co-administered with the artemisinin derivative. The in vivo EC50 values that corresponded to on average 95% of patients cured were much higher than the adjusted values derived from the in vitro IC50. The proportion clinically cured was not strongly influenced by changes in the parameters defining the age distribution of the initial parasite burden (mean age of 4 to 16 hours and the parasite multiplication factor every life cycle (ranging from 8 to 12 fold/cycle. The median parasite clearance times, however, lengthened as the standard deviation of the initial parasite burden increased (i

Remission of Grave's disease after oral anti-thyroid drug treatment.

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Ishtiaq, Osama; Waseem, Sabiha; Haque, M Naeemul; Islam, Najmul; Jabbar, Abdul

2009-11-01

To evaluate remission rate of anti-thyroid drug treatment in patients with Grave's disease, and to study the factors associated with remission. A cross sectional study. The Endocrine Department of the Aga Khan University Hospital, Karachi from 1999 to 2000. Seventy four patients of Grave's disease were recruited who were prescribed medical treatment. Grave's disease was diagnosed in the presence of clinical and biochemical hyperthyroidism along with anti-microsomal (AMA) and anti-thyroglobulin antibodies (ATA) and thyroid scan. These patients were prescribed oral anti-thyroid drugs using titration regime and followed at 3, 6, 12 and 18 months. Patients were categorized into two groups: "remission group" and "treatment failure group" and results were compared using a chi-square test, t-test and logistic regression model with significance at p disease on initial presentation.

The anti-hepatitis drug use effect and inventory management optimization from the perspective of hospital drug supply chain.

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Liu, Zhanyu

2017-09-01

By analyzing the current hospital anti hepatitis drug use, dosage, indications and drug resistance, this article studied the drug inventory management and cost optimization. The author used drug utilization evaluation method, analyzed the amount and kind distribution of anti hepatitis drugs and made dynamic monitoring of inventory. At the same time, the author puts forward an effective scheme of drug classification management, uses the ABC classification method to classify the drugs according to the average daily dose of drugs, and implements the automatic replenishment plan. The design of pharmaceutical services supply chain includes drug procurement platform, warehouse management system and connect to the hospital system through data exchange. Through the statistical analysis of drug inventory, we put forward the countermeasures of drug logistics optimization. The results showed that drug replenishment plan can effectively improve drugs inventory efficiency.

Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis.

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Juan D Unciti-Broceta

2015-06-01

Full Text Available African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.

[Recommendation for the prevention and treatment of non-steroidal anti-inflammatory drug-induced gastrointestinal ulcers and its complications].

Science.gov (United States)

2017-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are a broad class of non glucocorticoid drugs which are extensively used in anti-inflammatory, analgesic, and antipyretic therapies. However, NSAIDs may cause many side effects, most commonly in gastrointestinal(GI) tract. Cardiovascular system, kidney, liver, central nervous system and hematopoietic system are also involved. NSAID-induced GI side effects not only endanger the patients' health, increase mortality, but also greatly increase the cost of medical care. Therefore, how to reduce GI side effects is of particular concern to clinicians. The Chinese Rheumatism Data Center(CRDC) and Chinese Systemic Lupus Erythematosus Treatment and Research Group(CSTAR) compose a "Recommendation for the prevention and treatment of non-steroidal anti-inflammatory drug-induced gastrointestinal ulcers and its complications" , as following: (1) GI lesions are the most common side effects of NSAIDs. (2) NSAID-induced GI side effects include gastritis, esophagitis, gastric and duodenal ulcers, bleeding, perforation and obstruction. (3) With the application of capsule endoscopy and small intestinal endoscopy, growing attention is being paid to the NASID-induced small intestine mucosa damage, which is mainly erosion and ulcer. (4) Risk factors related to NSAID-induced GI ulcers include: Helicobacter pylori (Hp) infection, age> 65 years, past history of GI ulcers, high doses of NSAIDs, multiple-drug combination therapy, and comorbidities, such as cardiovascular disease and nephropathy.(5) GI and cardiovascular function should be evaluated before using NSAIDs and gastric mucosal protective agents. (6) The risk of GI ulcers and complications caused by selective cyclooxygenase-2 (COX-2) inhibitors is less than that of non-selective COX-2 inhibitors. (7)Hp eradication therapy helps to cure GI ulcers and prevent recurrence when Hp infection is positive in NSAID-induced ulcers. (8) Proton pump inhibitor (PPI) is the first choice for the

Parkinsonian syndromes presenting with circadian rhythm sleep disorder- advanced sleep-phase type.

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Shukla, Garima; Kaul, Bhavna; Gupta, Anupama; Goyal, Vinay; Behari, Madhuri

2015-01-01

Circadian rhythm sleep disorder-advanced sleep-phase type is a relatively uncommon disorder, mostly seen among the elderly population. Impaired circadian rhythms have been reported in neurodegenerative conditions; however, there are no reports of any circadian rhythm sleep disorder among patients with Parkinsonian syndromes. We report two patients who presented with this circadian rhythm disorder, and were then diagnosed with a Parkinsonian syndrome. The cases. A 65-year-old retired man presented with history of abrupt change in sleep schedules, sleeping around 6.30-7 p.m. and waking up around 3-4 a.m. for the last 2 months. On detailed examination, the patient was observed to have symmetrical bradykinesia and cogwheel rigidity of limbs. A diagnosis of multiple system atrophy was made, supported by MRI findings and evidence of autonomic dysfunction. Symptoms of change in sleep-wake cycles resolved over the next 1 year, while the patient was treated with dopaminergic therapy. A 47-year-old man, who was being evaluated for presurgical investigation for refractory temporal lobe epilepsy, presented with complaints suggestive of dysarthria, bradykinesia of limbs and frequent falls for 5 months. Simultaneously, he began to sleep around 7 p.m. and wake up at about 2-3 a.m. Examination revealed severe axial rigidity, restricted vertical gaze and bradykinesia of limbs. A diagnosis of progressive supranuclear palsy was made. This is the first report of Parkinson's plus syndromes presenting with a circadian rhythm sleep disorder-advanced sleep-phase type. More prospective assessment for circadian sleep disorders may introduce useful insights into similar associations. Copyright 2015, NMJI.

Anti-topoisomerase drugs as potent inducers of chromosomal aberrations

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Loredana Bassi

2000-12-01

Full Text Available DNA topoisomerases catalyze topological changes in DNA that are essential for normal cell cycle progression and therefore they are a preferential target for the development of anticancer drugs. Anti-topoisomerase drugs can be divided into two main classes: "cleavable complex" poisons and catalytic inhibitors. The "cleavable complex" poisons are very effective as anticancer drugs but are also potent inducers of chromosome aberrations so they can cause secondary malignancies. Catalytic inhibitors are cytotoxic but they do not induce chromosome aberrations. Knowledge about the mechanism of action of topoisomerase inhibitors is important to determine the best anti-topoisomerase combinations, with a reduced risk of induction of secondary malignancies.As topoisomerases de DNA catalisam alterações topológicas no DNA que são essenciais para a progressão do ciclo celular normal e, portanto, são um alvo preferencial para o desenvolvimento de drogas anticâncer. Drogas anti-topoisomerases podem ser divididas em duas classes principais: drogas anti-"complexos cliváveis" e inibidores catalíticos. As drogas anti-"complexos cliváveis" são muito eficazes como drogas anticancerígenas, mas são também potentes indutores de aberrações cromossômicas, podendo causar neoplasias malignas secundárias. Inibidores catalíticos são citotóxicos mas não induzem aberrações cromossômicas. Conhecimento a respeito do mecanismo de ação de inibidores de topoisomerases é importante para determinar as melhores combinações anti-topoisomerases, com um reduzido risco de indução de neoplasias malignas secundárias.

Glycaemic adverse drug reactions from anti-neoplastics used in ...

African Journals Online (AJOL)

235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...

Diffusion tensor imaging differentiates vascular parkinsonism from parkinsonian syndromes of degenerative origin in elderly subjects

Energy Technology Data Exchange (ETDEWEB)

Deverdun, Jérémy [Department of Neuroradiology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Laboratoire Charles Coulomb, CNRS UMR 5221 - Université Montpellier II, Montpellier (France); I2FH, Institut d’Imagerie Fonctionnelle Humaine, Hôpital Gui de Chauliac, CHRU de, Montpellier (France); Menjot de Champfleur, Sophie [Department of Neuroradiology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Clinique du Parc, Castelnau-le-Lez (France); Cabello-Aguilar, Simon [Department of Neuroradiology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); I2FH, Institut d’Imagerie Fonctionnelle Humaine, Hôpital Gui de Chauliac, CHRU de, Montpellier (France); Maury, Florence [Department of Neurology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Molino, François [Laboratoire Charles Coulomb, CNRS UMR 5221 - Université Montpellier II, Montpellier (France); Institut de Génomique Fonctionnelle, UMR 5203 - INSERM U661 - Université Montpellier II - Université, Montpellier I (France); Charif, Mahmoud [Department of Neurology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Leboucq, Nicolas [Department of Neuroradiology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Ayrignac, Xavier; Labauge, Pierre [Department of Neurology, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); and others

2014-11-15

Background and Purpose: The etiologic diagnosis of parkinsonian syndromes is of particular importance when considering syndromes of vascular or degenerative origin. The purpose of this study is to find differences in the white-matter architecture between those two groups in elderly patients. Materials and Methods: Thirty-five patients were prospectively included (multiple-system atrophy, n = 5; Parkinson's disease, n = 15; progressive supranuclear palsy, n = 9; vascular parkinsonism, n = 6), with a mean age of 76 years. Patients with multiple-system atrophy, progressive supranuclear palsy and Parkinson's disease were grouped as having parkinsonian syndromes of degenerative origin. Brain MRIs included diffusion tensor imaging. Fractional anisotropy and mean-diffusivity maps were spatially normalized, and group analyses between parkinsonian syndromes of degenerative origin and vascular parkinsonism were performed using a voxel-based approach. Results: Statistical parametric-mapping analysis of diffusion tensor imaging data showed decreased fractional anisotropy value in internal capsules bilaterally in patients with vascular parkinsonism compared to parkinsonian syndromes of degenerative origin (p = 0.001) and showed a lower mean diffusivity in the white matter of the left superior parietal lobule (p = 0.01). Fractional anisotropy values were found decreased in the middle cerebellar peduncles in multiple-system atrophy compared to Parkinson's disease and progressive supranuclear palsy. The mean diffusivity was increased in those regions for these subgroups. Conclusion: Clinically defined vascular parkinsonism was associated with decreased fractional anisotropy in the deep white matter (internal capsules) compared to parkinsonian syndromes of degenerative origin. These findings are consistent with previously published neuropathological data.

Diffusion tensor imaging differentiates vascular parkinsonism from parkinsonian syndromes of degenerative origin in elderly subjects

International Nuclear Information System (INIS)

Deverdun, Jérémy; Menjot de Champfleur, Sophie; Cabello-Aguilar, Simon; Maury, Florence; Molino, François; Charif, Mahmoud; Leboucq, Nicolas; Ayrignac, Xavier; Labauge, Pierre

2014-01-01

Background and Purpose: The etiologic diagnosis of parkinsonian syndromes is of particular importance when considering syndromes of vascular or degenerative origin. The purpose of this study is to find differences in the white-matter architecture between those two groups in elderly patients. Materials and Methods: Thirty-five patients were prospectively included (multiple-system atrophy, n = 5; Parkinson's disease, n = 15; progressive supranuclear palsy, n = 9; vascular parkinsonism, n = 6), with a mean age of 76 years. Patients with multiple-system atrophy, progressive supranuclear palsy and Parkinson's disease were grouped as having parkinsonian syndromes of degenerative origin. Brain MRIs included diffusion tensor imaging. Fractional anisotropy and mean-diffusivity maps were spatially normalized, and group analyses between parkinsonian syndromes of degenerative origin and vascular parkinsonism were performed using a voxel-based approach. Results: Statistical parametric-mapping analysis of diffusion tensor imaging data showed decreased fractional anisotropy value in internal capsules bilaterally in patients with vascular parkinsonism compared to parkinsonian syndromes of degenerative origin (p = 0.001) and showed a lower mean diffusivity in the white matter of the left superior parietal lobule (p = 0.01). Fractional anisotropy values were found decreased in the middle cerebellar peduncles in multiple-system atrophy compared to Parkinson's disease and progressive supranuclear palsy. The mean diffusivity was increased in those regions for these subgroups. Conclusion: Clinically defined vascular parkinsonism was associated with decreased fractional anisotropy in the deep white matter (internal capsules) compared to parkinsonian syndromes of degenerative origin. These findings are consistent with previously published neuropathological data

Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area.

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Paljetak, Hana Cipcic; Tomaskovic, Linda; Matijasic, Mario; Bukvic, Mirjana; Fajdetic, Andrea; Verbanac, Donatella; Peric, Mihaela

2017-01-01

Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Topical versus subconjunctival anti-vascular endothelial growth factor therapy (Bevacizumab, Ranibizumab and Aflibercept for treatment of corneal neovascularization

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Tariq Al-Debasi

2017-04-01

Anti-VEGF agents (Bevacizumab, Ranibizumab and Aflibercept seem to have a higher efficiency and efficacy for corneal NV treatment. Both subconjunctival therapy and topical therapy of bevacizumab prohibit corneal NV, while early treatment with subconjunctival administration of ranibizumab may successfully reduce corneal NV. Therefore, establishment of safe doses is highly important before these drugs can be involved in the clinical setting. Further investigations and studies are highly warranted to adjust the dose and route of administration for the antibodies directed against VEGF to be the key therapeutic agents in the corneal NV treatment.

Aspirin and its related non-steroidal anti-inflammatory drugs

African Journals Online (AJOL)

Aspirin and its related non-steroidal anti-inflammatory drugs. Aspirin or acetylsalicylic acid has been utilised by physicians for hundreds of years as an analgesic, anti-inflammatory and antipyretic (1). Derived from plant sources, such as the willow tree, it has the ability to induce apoptosis in cancer cells and stimulate.

77 FR 12063 - Joint Meeting of the Anti-Infective Drugs Advisory Committee and the Nonprescription Drugs...

Science.gov (United States)

2012-02-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Joint Meeting of the Anti-Infective Drugs Advisory Committee and the Nonprescription Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public...

Stockpiling anti-viral drugs for a pandemic: the role of Manufacturer Reserve Programs.

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Harrington, Joseph E; Hsu, Edbert B

2010-05-01

To promote stockpiling of anti-viral drugs by non-government organizations such as hospitals, drug manufacturers have introduced Manufacturer Reserve Programs which, for an annual fee, provide the right to buy in the event of a severe outbreak of influenza. We show that these programs enhance drug manufacturer profits but could either increase or decrease the amount of pre-pandemic stockpiling of anti-viral drugs.

Artificial intelligence in drug combination therapy.

Science.gov (United States)

Tsigelny, Igor F

2018-02-09

Currently, the development of medicines for complex diseases requires the development of combination drug therapies. It is necessary because in many cases, one drug cannot target all necessary points of intervention. For example, in cancer therapy, a physician often meets a patient having a genomic profile including more than five molecular aberrations. Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations. More recently, over the past several years, there has been an explosion in the available information related to the properties of drugs and the biomedical parameters of patients. For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. Moreover, during disease progression, the genetic profile can change. Thus, the ability to optimize drug combinations for each patient is rapidly moving beyond the comprehension and capabilities of an individual physician. This is the reason, that biomedical informatics methods have been developed and one of the more promising directions in this field is the application of artificial intelligence (AI). In this review, we discuss several AI methods that have been successfully implemented in several instances of combination drug therapy from HIV, hypertension, infectious diseases to cancer. The data clearly show that the combination of rule-based expert systems with machine learning algorithms may be promising direction in this field. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Immunogenicity of Anti-TNF-α Biotherapies

DEFF Research Database (Denmark)

Bendtzen, Klaus

2015-01-01

% of patients do not respond and about 50% of those who do loose response with time. Furthermore, safety may be compromised by immunogenicity with the induction of anti-drug-antibodies (ADA). Assessment of drug pharmacokinetics and ADA is increasingly recognized as a requirement for safe and rational use...... article - and the accompanying article - is to discuss the reasons for recommending assessments of circulating drug and ADA levels in patients treated with anti-TNF biopharmaceuticals and to detail some of the methodological issues that obscure cost-effective and safer therapies....

Effects of psychotropic drugs and psychiatric illness on vocational aptitude and interest assessment.

Science.gov (United States)

Helmes, E; Fekken, G C

1986-07-01

This study examined the vocational aptitude and interest scores of 326 inpatients at a large urban psychiatric hospital. The inpatient group performed significantly below the adult normative mean on eight of nine General Aptitude Test Battery (GATB) aptitude measures; the single exception was Verbal Aptitude. Further, GATB aptitude scores (adjusted for age and education) were significantly lower for patients who were receiving (N = 210) psychotropic medication than for patients who were not receiving (N = 114) psychotropic medication, again with the exception of Verbal Aptitude. Differentiation of patients into subsamples who were receiving particular drugs or drug combinations indicated that phenothiazines in combination with Anti-Parkinsonians were associated with the poorest GATB performances. Interestingly, self-reported vocational interests were not related in any systematic fashion to receiving medication. A variety of explanations that may account for these findings, including drug side-effects and severity or type of psychiatric disorder, were investigated. Implications for vocational counselors were discussed.

Advances in targeting the vacuolar proton-translocating ATPase (V-ATPase for anti-fungal therapy

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Summer R. Hayek

2014-01-01

Full Text Available Vacuolar proton-translocating ATPase (V-ATPase is a membrane-bound, multi-subunit enzyme that uses the energy of ATP hydrolysis to pump protons across membranes. V-ATPase activity is critical for pH homeostasis and organelle acidification as well as for generation of the membrane potential that drives secondary transporters and cellular metabolism. V-ATPase is highly conserved across species and is best characterized in the model fungus Saccharomyces cerevisiae (S. cerevisiae. However, recent studies in mammals have identified significant alterations from fungi, particularly in the isoform composition of the 14 subunits and in the regulation of complex disassembly. These differences could be exploited for selectivity between fungi and humans and highlight the potential for V-ATPase as an anti-fungal drug target. Candida albicans (C. albicans is a major human fungal pathogen and causes fatality in 35% of systemic infections, even with anti-fungal treatment. The pathogenicity of C. albicans correlates with environmental, vacuolar, and cytoplasmic pH regulation, and V-ATPase appears to play a fundamental role in each of these processes. Genetic loss of V-ATPase in pathogenic fungi leads to defective virulence, and a comprehensive picture of the mechanisms involved is emerging. Recent studies have explored the practical utility of V-ATPase as an anti-fungal drug target in C. albicans, including pharmacological inhibition, azole therapy, and targeting of downstream pathways. This overview will discuss these studies as well as hypothetical ways to target V-ATPase and novel high-throughput methods for use in future drug discovery screens.

Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats.

Science.gov (United States)

Wang, Yan-Yan; Wang, Yong; Jiang, Hai-Fei; Liu, Jun-Hua; Jia, Jun; Wang, Ke; Zhao, Fei; Luo, Min-Hua; Luo, Min-Min; Wang, Xiao-Min

2018-02-01

The glutamatergic projection from the motor cortex to the subthalamic nucleus (STN) constitutes the cortico-basal ganglia circuit and plays a critical role in the control of movement. Emerging evidence shows that the cortico-STN pathway is susceptible to dopamine depletion. Specifically in Parkinson's disease (PD), abnormal electrophysiological activities were observed in the motor cortex and STN, while the STN serves as a key target of deep brain stimulation for PD therapy. However, direct morphological changes in the cortico-STN connectivity in response to PD progress are poorly understood at present. In the present study, we used a trans-synaptic anterograde tracing method with herpes simplex virus-green fluorescent protein (HSV-GFP) to monitor the cortico-STN connectivity in a rat model of PD. We found that the connectivity from the primary motor cortex (M1) to the STN was impaired in parkinsonian rats as manifested by a marked decrease in trans-synaptic infection of HSV-GFP from M1 neurons to STN neurons in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. Ultrastructural analysis with electron microscopy revealed that excitatory synapses in the STN were also impaired in parkinsonian rats. Glutamatergic terminals identified by a specific marker (vesicular glutamate transporter 1) were reduced in the STN, while glutamatergic neurons showed an insignificant change in their total number in both the M1 and STN regions. These results indicate that the M1-STN glutamatergic connectivity is downregulated in parkinsonian rats. This downregulation is mediated probably via a mechanism involving the impairments of excitatory terminals and synapses in the STN. Copyright © 2017. Published by Elsevier Inc.

Therapeutic cloning in individual parkinsonian mice

Science.gov (United States)

Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

2009-01-01

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

Controlling pain during orthodontic fixed appliance therapy with non-steroidal anti-inflammatory drugs (NSAID): a randomized, double-blinded, placebo-controlled study.

Science.gov (United States)

Gupta, Mudit; Kandula, Srinivas; Laxmikanth, Sarala M; Vyavahare, Shreyas S; Reddy, Satheesha B H; Ramachandra, Chanila S

2014-11-01

Despite all the technological advances in orthodontics, orthodontic treatment still seems to involve some degree of discomfort and/or pain. Pain control during orthodontic therapy is of great concern to both orthodontists and patients. However, there has been limited research into controlling such pain. The purpose of this work was to assess patient-perceived pain following fixed orthodontic treatment and to evaluate the comparative analgesic efficacy of non-steroidal anti-inflammatory drugs for controlling pain. A total of 45 patients about to undergo fixed appliance orthodontic treatment were enrolled in this double-blind prospective study. Patients were evenly and randomly distributed in a blinded manner to one of three groups as follows: paracetamol/acetaminophen 500 mg thrice daily; placebo in the form of empty capsules; and etoricoxib 60 mg once daily. Drug administration began 1 h before initiating the bonding procedure and archwire placement, and given until the day 3. The pain perceived was recorded by the patients on a linear and graded Visual Analogue Scale at time intervals of 2 h after insertion of the appliance; 6 h thereafter and again at nighttime of the same day of the appointment; 24 h later and on the 2nd day at nighttime; 48 h after the appointment and on day 3 at nighttime. Our results revealed that moderately intense pain is associated with routine orthodontic treatment, and that the amount of pain individuals perceive varies widely. We observed statistically significant differences in the pain control among the three groups, and that etoricoxib 60 mg proved most efficient. Etoricoxib 60 mg is highly efficacious for controlling pain during fixed orthodontic appliance therapy.

The Anti-Osteoporotic Drug Preferences of Physiatrists: A Multicenter Descriptive Study

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Yeşim Gökçe Kutsal

2012-08-01

Full Text Available Aim: The purpose of this multicenter descriptive study is to determine the preferences of physiatrists in our country for anti-osteoporotic drugs in patients with primary and secondary osteoporosis. Materials and Methods: This study was carried out in 10 provinces of Turkey. The diagnosis of osteoporosis was based on World Health Organization criteria using dual-energy x-ray absorptiometry. Patients with a spine and/or hip T-score ≤-2.5 were considered as osteoporotic. 714 patients over 18 years old with primary or secondary osteoporosis were included in the study. In addition to socio-demographic characteristics and chronic use of medications and/or additional systemic diseases that cause secondary osteoporosis were questioned and antiosteoporotic drugs that are recommended by their physicians were recorded.Results: The physicians’ preferred vitamin D and calcium as the prior treatment both in primary and secondary osteoporosis. The most commonly used anti-osteoporotic agent was alendronate from the biphosphonate group. It was followed by ibandronate, risedronate, strontium ranelate, calcitonin, zoledronate, raloxifene, parathyroid hormone (PTH and hormone replacement therapy (HRT in the primary osteoporosis and risedronate, ibandronate, calcitonin, strontium ranelate, zoledronate, PTH, HRT and raloxifene in the secondary osteoporosis, respectively. Conclusion: The physician should choose the most suitable treatment for the patient based on fracture risk, medical history, previous treatments for osteoporosis, concomitant diseases, treatment-induced risks and benefits, and the relation between financial cost and potential benefit. (Turkish Journal of Osteoporosis 2012;18: 42-6

Use of nonsteroidal anti-inflammatory drugs among healthy people and specific cerebrovascular safety

DEFF Research Database (Denmark)

Fosbøl, Emil L; Olsen, Anne-Marie Schjerning; Olesen, Jonas Bjerring

2014-01-01

BACKGROUND: Nonsteroidal anti-inflammatory drugs can increase bleeding and thrombosis, but little is known about the cerebrovascular safety of these drugs, especially among healthy people. AIMS: The aim of this study was to examine the risk of ischemic and hemorrhagic stroke associated with the use...... stroke). RESULTS: We selected 1,028,437 healthy individuals (median age 39 years). At least one nonsteroidal anti-inflammatory drug was claimed by 44·7% of the study population, and the drugs were generally used for a short period of time and in low doses. High-dose ibuprofen and diclofenac were......·35-3·42)]. CONCLUSIONS: In healthy individuals, use of commonly available nonsteroidal anti-inflammatory drugs such as ibuprofen, diclofenac, and naproxen was associated with increased risk of stroke....

Rifampicin and anti-hypertensive drugs in chronic kidney disease: Pharmacokinetic interactions and their clinical impact

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A Agrawal

2016-01-01

Full Text Available Patients on dialysis have an increased incidence of tuberculosis (TB. Rifampicin, a first-line antitubercular therapy (ATT drug, is a potent inducer of hepatic cytochrome P450 (CYP. There is potential for pharmacokinetic interaction between rifampicin and anti-hypertensives that are CYP substrates: amlodipine and metoprolol. Therefore, hypertensive patients receiving rifampicin-based ATT are at risk for worsening of hypertension. However, this hypothesis has not yet been systematically studied. In this prospective study, hypertensive CKD 5D patients with TB were followed after rifampicin initiation. Blood pressure (BP was ≤140/90 mmHg with stable anti-HT requirement at inclusion. Serum amlodipine, metoprolol, and prazosin levels were estimated by high-performance liquid chromatography at baseline and 3, 7, 10, and 14 days after rifampicin initiation. BP and anti-HT requirement were monitored for 2 weeks or until stabilization. All 24 patients in the study had worsening of hypertension after rifampicin and 83.3% required increase in drugs to maintain BP 50% in all patients and became undetectable in 50-75%. Drug requirement increased from 4.5 ± 3.6 to 8.5 ± 6.4 units (P < 0.0001. Mean time to first increase in dose was 6.5 ± 3.6 days. Eleven (46% patients experienced a hypertensive crisis at 9.1 ± 3.8 days. Three of them had a hypertensive emergency with acute pulmonary edema. In two patients, rifampicin had to be discontinued to achieve BP control. In conclusion, rifampicin caused a significant decrease in blood levels of commonly used anti hypertensives. This decrease in levels correlated well with worsening of hypertension. Thus, we suggest very close BP monitoring in CKD patients after rifampicin initiation.

Improved consistency in dosing anti-tuberculosis drugs in Taipei, Taiwan.

Science.gov (United States)

Chiang, Chen-Yuan; Yu, Ming-Chih; Shih, Hsiu-Chen; Yen, Muh-Yong; Hsu, Yu-Ling; Yang, Shiang-Lin; Lin, Tao-Ping; Bai, Kuan-Jen

2012-01-01

It was reported that 35.5% of tuberculosis (TB) cases reported in 2003 in Taipei City had no recorded pre-treatment body weight and that among those who had, inconsistent dosing of anti-TB drugs was frequent. Taiwan Centers for Disease Control (CDC) have taken actions to strengthen dosing of anti-TB drugs among general practitioners. Prescribing practices of anti-TB drugs in Taipei City in 2007-2010 were investigated to assess whether interventions on dosing were effective. Lists of all notified culture positive TB cases in 2007-2010 were obtained from National TB Registry at Taiwan CDC. A medical audit of TB case management files was performed to collect pretreatment body weight and regimens prescribed at commencement of treatment. Dosages prescribed were compared with dosages recommended. The proportion of patients with recorded pre-treatment body weight was 64.5% in 2003, which increased to 96.5% in 2007-2010 (pTaipei City has remarkably improved after health authorities implemented a series of interventions.

A systematic review of anti-thrombotic therapy in epistaxis.

Science.gov (United States)

Musgrave, K M; Powell, J

2016-12-01

There is limited guidance available to clinicians regarding the management of antithrombotic therapy during epistaxis, whilst there has been an increase in the use of anticoagulation and antiplatelet therapy. In addition, the introduction of direct oral anticoagulants (DOACs), such as dabigatran and rivaroxaban, over the last decade has significantly increased the complexity of managing the anticoagulated epistaxis patient. We undertook a systemic literature review investigating potential management strategies for each class of anti-thrombotic therapy during epistaxis. A PubMED and Cochrane Library search was performed on 10/03/16 using, but not limited to, the search terms epistaxis, nosebleed, nose bleeding, nasal haemorrhage, nasal bleeding AND each of the following search terms: antithrombotic, anticoagulant, antiplatelet, aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, apixaban and tranexamic acid. This yielded 3815 results, of which 29 were considered relevant. Other sources such as national and international guidelines related to the management of anti-thrombotics were also utilised. We present the findings related to the management of each class of anti-thrombotic therapy during epistaxis. Overall we found a lack of evidence regarding this topic and further high quality research is needed. This is an area growing in complexity and the support of colleagues in Haematology and Cardiology is increasingly important.

Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death

DEFF Research Database (Denmark)

De Bruin, M L; Pettersson, M; Meyboom, R H B

2005-01-01

AIMS: Drug-induced QTc-prolongation, resulting from inhibition of HERG potassium channels may lead to serious ventricular arrhythmias and sudden death. We studied the quantitative anti-HERG activity of pro-arrhythmic drugs as a risk factor for this outcome in day-to-day practice. METHODS...... defined as reports of cardiac arrest, sudden death, torsade de pointes, ventricular fibrillation, and ventricular tachycardia (n = 5591), and compared with non-cases regarding the anti-HERG activity, defined as the effective therapeutic plasma concentration (ETCPunbound) divided by the HERG IC50 value......, of suspected drugs. We identified a significant association of 1.93 (95% CI: 1.89-1.98) between the anti-HERG activity of drugs, measured as log10 (ETCPunbound/IC50), and reporting of serious ventricular arrhythmias and sudden death to the WHO-UMC database. CONCLUSION: Anti-HERG activity is associated...

Evidence-Based Design of Fixed-Dose Combinations: Principles and Application to Pediatric Anti-Tuberculosis Therapy.

Science.gov (United States)

Svensson, Elin M; Yngman, Gunnar; Denti, Paolo; McIlleron, Helen; Kjellsson, Maria C; Karlsson, Mats O

2018-05-01

Fixed-dose combination formulations where several drugs are included in one tablet are important for the implementation of many long-term multidrug therapies. The selection of optimal dose ratios and tablet content of a fixed-dose combination and the design of individualized dosing regimens is a complex task, requiring multiple simultaneous considerations. In this work, a methodology for the rational design of a fixed-dose combination was developed and applied to the case of a three-drug pediatric anti-tuberculosis formulation individualized on body weight. The optimization methodology synthesizes information about the intended use population, the pharmacokinetic properties of the drugs, therapeutic targets, and practical constraints. A utility function is included to penalize deviations from the targets; a sequential estimation procedure was developed for stable estimation of break-points for individualized dosing. The suggested optimized pediatric anti-tuberculosis fixed-dose combination was compared with the recently launched World Health Organization-endorsed formulation. The optimized fixed-dose combination included 15, 36, and 16% higher amounts of rifampicin, isoniazid, and pyrazinamide, respectively. The optimized fixed-dose combination is expected to result in overall less deviation from the therapeutic targets based on adult exposure and substantially fewer children with underexposure (below half the target). The development of this design tool can aid the implementation of evidence-based formulations, integrating available knowledge and practical considerations, to optimize drug exposures and thereby treatment outcomes.

HAART (Highly Active Anti-Retroviral Therapy : An overview

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Praful Pande

2014-01-01

activation, restoration of lymph node architecture, clinical improvement, prolonged survival, fewer opportunistic infections and HIV - associated malignancies. Problem with therapy are pill burden, non-availability of drugs, food and storage restrictions, drug-drug interactions, severe side-effects, reduction in quality of life measures, emergence of multiple drug resistance mutations.

Electrochemical studies of ropinirole, an anti-Parkinson's disease drug

Indian Academy of Sciences (India)

The oxidation behaviour of a potent anti-Parkinson's disease drug ropinirole hydrochloride was investigated over a wide pH range in aqueous solution at glassy carbon electrode using cyclic and square-wave voltammetry. The oxidation of drug is a pH dependent irreversible process and occurs in two steps.

Systemic and localized infection by Candida species in patients with rheumatic diseases receiving anti-TNF therapy

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Nadia E. Aikawa

Full Text Available ABSTRACT Objective: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. Methods: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. Results: 194 patients [67 with rheumatoid arthritis (RA, 47 with ankylosing spondylitis (AS, 36 with juvenile idiopathic arthritis (JIA, 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42 ± 16 years, with 68 (35% male and mean disease duration of 15 ± 10 years. Sixty-four (33% patients were receiving adalimumab, 59 (30% etanercept and 71 (36% infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5% patient had localized fungal infection (vaginal candidiasis. None of the patients included had systemic candidiasis with positive blood cultures for fungi or PCR positive for Candida spp. in peripheral blood sample. Conclusions: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use.

The susceptibility of anti-tuberculosis drug-induced liver injury and chronic hepatitis C infection: A systematic review and meta-analysis.

Science.gov (United States)

Chang, Tien-En; Huang, Yi-Shin; Chang, Chih-Hao; Perng, Chin-Lin; Huang, Yi-Hsiang; Hou, Ming-Chih

2018-02-01

Anti-tuberculosis drug-induced liver injury (ATDILI) is a major safety concern in the treatment of tuberculosis (TB). The impact of chronic hepatitis C (CHC) infection on the risk of ATDILI is still controversial. We aimed to assess the influence of CHC infection on ATDILI through a systematic review and meta-analysis. We systemically reviewed all English-language literature in the major medical databases with the subject search terms "anti-tuberculosis drug-induced liver injury" and "anti-tuberculosis drug-induced hepatotoxicity". We then performed a systematic review and meta-analysis of the papers relevant to hepatitis C in qualified publications. A total of 14 studies were eligible for analysis, which included 516 cases with ATDILI and 4301 controls without ATDILI. The pooled odds ratio (OR) of all studies for CHC infection to ATDILI was 3.21 (95% confidence interval (CI): 2.30-4.49). Subgroup analysis revealed that the CHC carriers had a higher risk of ATDILI than those without CHC both in Asians (OR = 2.96, 95% CI: 1.79-4.90) and Caucasians (OR = 4.07, 95% CI: 2.70-6.14), in those receiving standard four combination anti-TB therapy (OR = 2.94, 95% CI: 1.95-4.41) and isoniazid monotherapy (OR = 4.18, 95% CI: 2.36-7.40), in those with a strict definition of DILI (serum alanine aminotransferase [ALT] > 5 upper limit of normal value [ULN], OR = 2.59, 95% CI: 1.58-4.25) and a loose definition of DILI (ALT > 2 or 3 ULN, OR = 4.34, 95% CI: 2.96-6.37), and in prospective studies (OR = 4.16, 95% CI: 2.93-5.90) and case-control studies (OR = 2.43, 95% CI: 1.29-4.58). This meta-analysis suggests that CHC infection may increase the risk of ATDILI. Regular liver tests are mandatory for CHC carriers under anti-TB therapy. Copyright © 2017. Published by Elsevier Taiwan LLC.

Pharmacogenetics of Anti-Diabetes Drugs

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Johanna K. DiStefano

2010-08-01

Full Text Available A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D. In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs, meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4 inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of ‘response’ can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for “individualized medicine” for patients with T2D.

Potential drug therapies for the treatment of fibromyalgia.

Science.gov (United States)

Lawson, Kim

2016-09-01

Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non-pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use. A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and α2δ ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies. Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms.

Is anti-platelet therapy interruption a real clinical issue? Its implications in dentistry and particularly in periodontics

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Kumar A

2009-01-01

Full Text Available The use of anti-platelet therapy has reduced the mortality and morbidity of cardiovascular disease remarkably. A considerable number of patients presenting before a dentist or periodontist give a history of anti-platelet therapy. A clinical dilemma whether to discontinue the anti-platelet therapy or continue the same always confronts the practitioner. Diverse opinions exist regarding the management of such patients. While one group of researchers advise continuation of anti-platelet therapy rather than invite remote, but possible, thromboembolic events, another group encourages discontinuation for variable periods. This study aims at reviewing the current rationale of anti-platelet therapy and the various options available to a clinician, with regard to the management of a patient under anti-platelet therapy. Current recommendations and consensus favour no discontinuation of anti-platelet therapy. This recommendation, however, comes with a rider to use caution and consider other mitigating factors as well. With a large number of patients giving a history of anti-platelet therapy, the topic is of interest and helps a clinician to arrive at a decision.

Doxorubicin-conjugated bacteriophages carrying anti-MHC class I chain-related A for targeted cancer therapy in vitro

Directory of Open Access Journals (Sweden)

Phumyen A

2014-11-01

Full Text Available Achara Phumyen,1–3 Siriporn Jantasorn,1 Amonrat Jumnainsong,1 Chanvit Leelayuwat1–4 1The Centre for Research and Development of Medical Diagnostic Laboratories (CMDL, Faculty of Associated Medical Sciences, 2The Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, 3Research Cluster: Specific Health Problem of Grater Maekong Subregion (SHeP-GMS, 4Department of Clinical Immunology and Transfusion Sciences, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand Background: Cancer therapy by systemic administration of anticancer drugs, besides the effectiveness shown on cancer cells, demonstrated the side effects and cytotoxicity on normal cells. The targeted drug-carrying nanoparticles may decrease the required drug concentration at the site and the distribution of drugs to normal tissues. Overexpression of major histocompatibility complex class I chain–related A (MICA in cancer is useful as a targeted molecule for the delivery of doxorubicin to MICA-expressing cell lines. Methods: The application of 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide (EDC chemistry was employed to conjugate the major coat protein of bacteriophages carrying anti-MICA and doxorubicin in a mildly acid condition. Doxorubicin (Dox on phages was determined by double fluorescence of phage particles stained by M13-fluorescein isothiocyanate (FITC and drug autofluorescence by flow cytometry. The ability of anti-MICA on phages to bind MICA after doxorubicin conjugation was evaluated by indirect enzyme-linked immunosorbent assay. One cervical cancer and four cholangiocarcinoma cell lines expressing MICA were used as models to evaluate targeting activity by cell cytotoxicity test. Results: Flow cytometry and indirect enzyme-linked immunosorbent assay demonstrated that most of the phages (82% could be conjugated with doxorubicin, and the Dox-carrying phage-displaying anti-MICA (Dox-phage remained the binding activity against MICA

Depressive disorders and anti-parkinson drug treatment

DEFF Research Database (Denmark)

Brandt-Christensen, M; Lopez, A G; Nilsson, F M

2007-01-01

OBJECTIVE: To estimate the rate of treatment with anti-parkinson drugs (APD) among patients with depression. METHOD: In a nationwide case register linkage study, all persons with a main diagnosis of depression during 5 years were identified. A control group of persons with diagnoses of osteoarthr...... that prescription of APD reflects the presence of Parkinson's disease, results support a positive statistical association between depressive disorders and Parkinson's disease.......OBJECTIVE: To estimate the rate of treatment with anti-parkinson drugs (APD) among patients with depression. METHOD: In a nationwide case register linkage study, all persons with a main diagnosis of depression during 5 years were identified. A control group of persons with diagnoses...... of osteoarthritis was included. The subsequent risk of getting treatment with APD was estimated for the two groups. Statistical analyses involved Poisson's regression and competing risk models. RESULTS: A total of 14 991 persons were included. The rate of getting APD was 2.57 (95% CI: 1.46-4.52) times higher...

Future of anti-addiction vaccines.

Science.gov (United States)

Kosten, Thomas R

2005-01-01

The medical rational for using anti-drug antibodies in the serum as a treatment is to reduce drug levels in the brain and to bind drug before it enters the brain. Drugs of abuse are small molecules that can readily cross the blood brain barrier, while antibodies are larger molecules that cannot get into the brain. Thus, any drug that is bound to antibody also cannot cross the blood brain barrier and cannot enter the brain. Active anti-drug vaccines stimulate the body to makes its own antibodies, but the small size of abused drugs prevents them from stimulating an immune response. Thus, individuals do not ordinarily produce antibodies to abused drugs, and vaccines to stimulate antibodies are made by chemically linking these abused drugs to toxins such as cholera toxin. Alternatively, passive immunotherapy uses monoclonal antibodies that are generated in a laboratory and then administered via intravenous injection. Antibodies can be used to treat drug overdose; to reduce drug use relapse; or to protect certain at risk populations who have not yet become drug dependent. The advantages of anti-addiction vaccines are that antibodies target the drug, not the drug's sites of action in the brain and antibody binding inactivates the drug. These vaccines can complement behavioral and other medical therapies with minimal side effects and are not addictive like some chemical agonists. Technology advances in manufacturing and delivery systems will improve future anti-addiction vaccines, but social acceptance of anti-addiction vaccines will depend on substance abuse program staff and the families of substance abusers, who have some values that oppose medical solutions to addictive diseases and view addictions as moral problems.

REHABILITATION THERAPY VERSUS DRUG THERAPY IN PATIENTS WITH LUMBAR DISC DEGENERATION

Directory of Open Access Journals (Sweden)

BROSCATEAN, Emanuela-Flavia

2013-12-01

Full Text Available Lumbar disc degeneration is a disorder whose clinical manifestations are represented by episodic pain in the lumbar spine, without lumbar blockage and minor muscle contraction. Because lumbalgia caused by lumbar disc degeneration is not always very high intensity pain, the easiest to apply treatment is drug therapy. The aim of this study was to analyze the potential role of rehabilitation treatment in the recovery of patients and the prevention of complications compared to drug therapy alone. The study included 28 patients (17 women and 11 men aged between 23-60 years, assigned to two groups: 20 patients who received rehabilitation treatment (consisting of massage, kinesiotherapy, hydrokinesiotherapy, electrotherapy and medication and 8 patients who received drug treatment consisting of anti-inflammatory and analgesic drugs. The treatment duration was 10 days. For the evaluation of pain, the visual analogue scale was used, for the degree of disability, the Oswestry questionnaire, and for joint mobility and muscle strength, articular and muscular testing. At the end of treatment, the study group compared to the control group had a statistically significant result for pain (p=0.001, as well as for the Oswestry score (p=0.030. The mean age of the patients was 35.51±3.026, which shows an increased incidence among young adults. A possible connection between the development of the disease in women and age less than 45 years was also investigated, but the result was not statistically significant, p=0.22. Our data suggest the fact that rehabilitation treatment plays an important role in the reduction of pain and the improvement of the quality of life of patients with lumbar disc degeneration by decreasing the degree of disability. In the future, it can be proposed to monitor patients with lumbar disc degeneration over a longer time period in order to see the effects of kinetic rehabilitation programs in relation to the delay of chronicization. As

Drug therapy smartens up

Science.gov (United States)

Martin, Christian

2015-11-01

The submission of the first 'smart pill' for market approval, combined with progress in the European nanomedicine landscape, illustrates the positive outlook for drug therapy and health monitoring, explains Christian Martin.

Amyloid-related biomarkers and axonal damage proteins in parkinsonian syndromes

DEFF Research Database (Denmark)

Bech, Sara; Hjermind, Lena E; Salvesen, Lisette

2012-01-01

Clinical differentiation between parkinsonian syndromes (PS) remains a challenge despite well-established clinical diagnostic criteria. Specific diagnostic biomarkers have yet to be identified, though in recent years, studies have been published on the aid of certain brain related proteins (BRP) ...

A Pilot Trial of Jawarish Amla as Adjuvant to Anti-Tubercular Treatment Drugs for Control of Adverse Reactions in DOTS Regime in Pulmonary TB

OpenAIRE

Sherwani, Arish Mohammad Khan; Zulkifle, Mohammad; Rehmatulla,

2013-01-01

Background and objectives One of the greatest challenges of health care systems at the dawn of the 21st century is tuberculosis (TB). Drug resistant strains of TB are becoming a global public health risk. These strains commonly appear due to faulty therapies. Patients frequently stop treatment due to the toxicity of anti-tubercular treatment (ATT) drugs. Amla (Emblica officinalis) is a well-known Unani single drug. Jawarish amla is a Unani compound formulation which is commonly used to admini...

Management of noninfectious posterior uveitis with intravitreal drug therapy

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Tan HY

2016-10-01

Full Text Available Hui Yi Tan,1 Aniruddha Agarwal,2 Cecilia S Lee,3 Jay Chhablani,4 Vishali Gupta,5 Manoj Khatri,6 Jayabalan Nirmal,7 Carlos Pavesio,8 Rupesh Agrawal1,7–9 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Department of Vitreoretina, Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 3Department of Ophthalmology, University of Washington, Seattle, WA, USA; 4Department of Vitreoretina, L V Prasad Eye Institute, Hyderabad, Telangana, 5Department of Retina and Uvea, Post Graduate Institute of Medical Education and Research, Chandigarh, 6Department of Retina, Rajan Eye Care Hospital, Chennai, Tamil Nadu, India; 7School of Material Science and Engineering, Nanyang Technological University, Singapore; 8Department of Medical Retina, Moorfields Eye Hospital, NHS Foundation Trust, London, UK; 9Department of Ophthalmology, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore Abstract: Uveitis is an important cause of vision loss worldwide due to its sight-threatening complications, especially cystoid macular edema, as well as choroidal neovascularization, macular ischemia, cataract, and glaucoma. Systemic corticosteroids are the mainstay of therapy for noninfectious posterior uveitis; however, various systemic side effects can occur. Intravitreal medication achieves a therapeutic level in the vitreous while minimizing systemic complications and is thus used as an exciting alternative. Corticosteroids, antivascular endothelial growth factors, immunomodulators such as methotrexate and sirolimus, and nonsteroidal anti-inflammatory drugs are currently available for intravitreal therapy. This article reviews the existing literature for efficacy and safety of these various options for intravitreal drug therapy for the management of noninfectious uveitis (mainly intermediate, posterior, and panuveitis. Keywords: intravitreal therapy, noninfectious uveitis, posterior uveitis

Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs)

DEFF Research Database (Denmark)

Nissen, Christoffer V; Bindslev-Jensen, Carsten; Mørtz, Charlotte G

2015-01-01

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are reported to be the second most common cause of drug hypersensitivity. In 2011, experts from the EAACI/ENDA group and GA(2)LEN proposed a new classification system for NSAID hypersensitivity. The aim of this study was to classify...... responders reacted to non-pyrazolone drugs. Only one patient could not be classified according to the EAACI/ENDA system. An overlap between respiratory and cutaneous symptoms was found in 15/39 (38%) of patients. CONCLUSIONS: All but one of our patients could be classified according to the EAACI...

Metabolomics has the potential to improve drug therapy

DEFF Research Database (Denmark)

Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder

2014-01-01

Until now drug therapy has primarily been controlled by dose titration on the basis of effects and side effects. However, a lot of people being treated with a drug experience too little effect or too many side effects. Therefore it will be advantageous to improve drug therapy and make it even more...

Mucosal healing with thalidomide in refractory Crohn's disease patients intolerant of anti-TNF-α drugs: report of 3 cases and literature review.

Science.gov (United States)

Scribano, Maria Lia; Cantoro, Laura; Marrollo, Marzia; Cosintino, Rocco; Kohn, Anna

2014-07-01

Thalidomide is an oral immunomodulatory and anti-inflammatory drug with antitumor necrosis factor-α (TNF-α) activity. Several case reports and some clinical trials have demonstrated its efficacy in the treatment of refractory Crohn's disease (CD). We report the effect and tolerability of thalidomide in 3 patients with moderate-to-severe CD who were not responsive to anti-TNF-α therapies, and review the relevant literature. The first case is of a 28-year-old female affected by Crohn's colitis complicated by a severe fistulizing perianal disease; she was treated with infliximab, adalimumab, and certolizumab pegol, which were stopped because of intolerance. The second case is of a 39-year-old female with fistulizing ileocolitis complicated by severe arthralgias and perianal disease with loss of response to infliximab and intolerance of certolizumab pegol. The third case is of a 39-year-old male with gastric and ileocolonic CD refractory to immunosuppressors and intolerant of infliximab. All the 3 cases achieved complete clinical remission and endoscopic healing of mucosal lesions at a low dose of thalidomide (50 to 150 mg/d). In our CD patients who experienced loss of response or were unable to tolerate anti-TNF-α drugs, thalidomide was an effective and well-tolerated therapy for inducing and maintaining long-term remission.

Novel approaches in anti-arenaviral drug development

International Nuclear Information System (INIS)

Lee, Andrew M.; Pasquato, Antonella; Kunz, Stefan

2011-01-01

Hemorrhagic fevers caused by arenaviruses are among the most devastating emerging human diseases. Considering the number of individuals affected, the current lack of a licensed vaccine, and the limited therapeutic options, arenaviruses are arguably among the most neglected tropical pathogens and the development of efficacious anti-arenaviral drugs is of high priority. Over the past years significant efforts have been undertaken to identify novel potent inhibitors of arenavirus infection. High throughput screening of small molecule libraries employing pseudotype platforms led to the discovery of several potent and broadly active inhibitors of arenavirus cell entry that are effective against the major hemorrhagic arenaviruses. Mechanistic studies revealed that these novel entry inhibitors block arenavirus membrane fusion and provided novel insights into the unusual mechanism of this process. The success of these approaches highlights the power of small molecule screens in antiviral drug discovery and establishes arenavirus membrane fusion as a robust drug target. These broad screenings have been complemented by strategies targeting cellular factors involved in productive arenavirus infection. Approaches targeting the cellular protease implicated in maturation of the fusion-active viral envelope glycoprotein identified the proteolytic processing of the arenavirus glycoprotein precursor as a novel and promising target for anti-arenaviral strategies.

Availability, price and affordability of anti-tuberculosis drugs in Europe: a TBNET survey

NARCIS (Netherlands)

Günther, Gunar; Gomez, Gabriela B.; Lange, Christoph; Rupert, Stephan; van Leth, Frank; Andrejak, Claire; Pieridou-Bagatzouni, Despo; Anderson, Aase Bengard; Bojovic, Olivera; Bothamley, Graham; Bruchfeld, Judith; Codecasa, Luigi R.; Danilovits, Manfred; Davidaviciene, Edita; Dalemo, Paulina; Dimopoulos, Giorgos; Duarte, Raquel; Hafizi, Hasan; Horvath, Ildiko; Eyuboglu, Fusun; Ibraim, Elmira; Jankovic, Mateja; Kan, Boris; Kopecka, Emilia; Kruczak, Katarzyna; Kutsyna, Galyna; de lange, Wiel; Leimane, Vaira; Mack, Ulrich; Manzano, Juan Ruiz; Markova, Roumania; McDonald, Colm; McLaughlin, Anne-Marie; Mulliqi, Gjyle; Muylle, Inge; Pesut, Dragica; Polcova, Veronika; Rumetshofer, Rudolf; Rusu, Doina; Skrahina, Alena; Spiric, Nicolina; Solovic, Ivan; Svetina-Sorli, Petra; Vasakova, Martina; Vasankari, Tuula; Viiklepp, Piret; Wirz, Gil; Zakoska, Maja; Zellweger, Jean-Pierre

2015-01-01

Data on availability and cost of anti-tuberculosis (TB) drugs in relation to affordability at national level are scarce. We performed a cross-sectional study on availability and cost of anti-TB drugs at major TB-reference centres in 37 European countries. Costs of standardised treatment regimens

Quorum sensing Inhibitors as anti-pathogenic drugs

DEFF Research Database (Denmark)

Rasmussen, Thomas Bovbjerg; Givskov, Michael Christian

2006-01-01

as well as elevated tolerance to the activity of the innate immune system. Gram-negative bacteria commonly use N-acyl homoserine lactones (AHL) as QS signal molecules. The use of signal molecule based drugs to attenuate bacterial pathogenecity rather than bacterial growth is attractive for several reasons......, particularly considering the emergence of increasingly antibiotic-resistant bacteria. Compounds capable of this type of interference have been termed anti-pathogenic drugs. A large variety of synthetic AHL analogues and natural products libraries have been screened and a number of QS inhibitors (QSI) have been...

Brain MR Contribution to the Differential Diagnosis of Parkinsonian Syndromes: An Update

Directory of Open Access Journals (Sweden)

Giovanni Rizzo

2016-01-01

Full Text Available Brain magnetic resonance (MR represents a useful and feasible tool for the differential diagnosis of Parkinson’s disease. Conventional MR may reveal secondary forms of parkinsonism and may show peculiar brain alterations of atypical parkinsonian syndromes. Furthermore, advanced MR techniques, such as morphometric-volumetric analyses, diffusion-weighted imaging, diffusion tensor imaging, tractography, proton MR spectroscopy, and iron-content sensitive imaging, have been used to obtain quantitative parameters useful to increase the diagnostic accuracy. Currently, many MR studies have provided both qualitative and quantitative findings, reflecting the underlying neuropathological pattern of the different degenerative parkinsonian syndromes. Although the variability in the methods and results across the studies limits the conclusion about which technique is the best, specific radiologic phenotypes may be identified. Qualitative/quantitative MR changes in the substantia nigra do not discriminate between different parkinsonisms. In the absence of extranigral abnormalities, the diagnosis of PD is more probable, whereas basal ganglia changes (mainly in the putamen suggest the diagnosis of an atypical parkinsonian syndrome. In this context, changes in pons, middle cerebellar peduncles, and cerebellum suggest the diagnosis of MSA, in midbrain and superior cerebellar peduncles the diagnosis of PSP, and in whole cerebral hemispheres (mainly in frontoparietal cortex with asymmetric distribution the diagnosis of Corticobasal Syndrome.

Pathogenesis of Brain Edema and Investigation into Anti-Edema Drugs

Science.gov (United States)

Michinaga, Shotaro; Koyama, Yutaka

2015-01-01

Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them. PMID:25941935

Ethnobotany and ethnopharmacy--their role for anti-cancer drug development.

Science.gov (United States)

Heinrich, Michael; Bremner, Paul

2006-03-01

Local and traditional knowledge has been the starting point for many successful drug development projects over the last decades. Here we discuss some examples of anti-cancer drugs which have had enormous impact as anti-cancer agents (camptothecan, taxol and derivatives) and a few examples of drugs currently under various stages of preclinical development. Ethnobotanists investigate the relationship between humans and plants in all its complexity, and such research is generally based on a detailed observation and study of the use a society makes of plants. The requirements of modern research on natural products as, for example, outlined in the Convention on Biological Diversity (Rio Convention) and the overall approach in ethnobotanical research are also discussed. Selected phytochemical-pharmacological studies based on traditional plant use are used to highlight the potential of ethnobotany driven anti-cancer research. The link between traditionally used plants and targets of the NF-kappaB pathway is discussed using on an EU-funded, multidisciplinary project as an example. Lastly the potential of chemopreventive agents derived from traditional food plants is briefly addressed.

Focused and Sustained Attention Is Modified by a Goal-Based Rehabilitation in Parkinsonian Patients.

Science.gov (United States)

Ferrazzoli, Davide; Ortelli, Paola; Maestri, Roberto; Bera, Rossana; Gargantini, Roberto; Palamara, Grazia; Zarucchi, Marianna; Giladi, Nir; Frazzitta, Giuseppe

2017-01-01

Rehabilitation for patients with Parkinson's disease (PD) is based on cognitive strategies that exploit attention. Parkinsonians exhibit impairments in divided attention and interference control. Nevertheless, the effectiveness of specific rehabilitation treatments based on attention suggests that other attentional functions are preserved. Data about attention are conflicting in PD, and it is not clear whether rehabilitative treatments that entail attentional strategies affect attention itself. Reaction times (RTs) represent an instrument to explore attention and investigate whether changes in attentional performances parallel rehabilitation induced-gains. RTs of 103 parkinsonian patients in "on" state, without cognitive deficits, were compared with those of a population of 34 healthy controls. We studied those attentional networks that subtend the use of cognitive strategies in motor rehabilitation: alertness and focused and sustained attention, which is a component of the executive system. We used visual and auditory RTs to evaluate alertness and multiple choices RTs (MC RTs) to explore focused and sustained attention. Parkinsonian patients underwent these tasks before and after a 4-week multidisciplinary, intensive and goal-based rehabilitation treatment (MIRT). Unified Parkinson's Disease Rating Scale (UPDRS) III and Timed Up and Go test (TUG) were assessed at the enrollment and at the end of MIRT to evaluate the motor-functional effectiveness of treatment. We did not find differences in RTs between parkinsonian patients and controls. Further, we found that improvements in motor-functional outcome measures after MIRT ( p attention, are preserved in "on" state. This explains why Parkinsonians benefit from a goal-based rehabilitation that entails the use of attention. The reduction in MC RTs suggests a positive effect of MIRT on the executive component of attention and indicates that this type of rehabilitation provides benefits by exploiting executive functions

Mucuna pruriens seed extract reduces oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in paraquat-induced Parkinsonian mouse model.

Science.gov (United States)

Yadav, Satyndra Kumar; Prakash, Jay; Chouhan, Shikha; Singh, Surya Pratap

2013-06-01

Parkinson's disease (PD) is a neurodegenerative disease which causes rigidity, resting tremor and postural instability. Treatment for this disease is still under investigation. Mucuna pruriens (L.), is a traditional herbal medicine, used in India since 1500 B.C., as a neuroprotective agent. In this present study, we evaluated the therapeutic effects of aqueous extract of M. pruriens (Mp) seed in Parkinsonian mouse model developed by chronic exposure to paraquat (PQ). Results of our study revealed that the nigrostriatal portion of Parkinsonian mouse brain showed significantly increased levels of nitrite, malondialdehyde (MDA) and reduced levels of catalase compared to the control. In the Parkinsonian mice hanging time was decreased, whereas narrow beam walk time and foot printing errors were increased. Treatment with aqueous seed extract of Mp significantly increased the catalase activity and decreased the MDA and nitrite level, compared to untreated Parkinsonian mouse brain. Mp treatment also improved the behavioral abnormalities. It increased hanging time, whereas it decreased narrow beam walk time and foot printing error compared to untreated Parkinsonian mouse brain. Furthermore, we observed a significant reduction in tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra (SN) and striatum region of the brain, after treatment with PQ which was considerably restored by the use of Mp seed extract. Our result suggested that Mp seed extract treatment significantly reduced the PQ induced neurotoxicity as evident by decrease in oxidative damage, physiological abnormalities and immunohistochemical changes in the Parkinsonian mouse. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.

Science.gov (United States)

Trelle, Sven; Reichenbach, Stephan; Wandel, Simon; Hildebrand, Pius; Tschannen, Beatrice; Villiger, Peter M; Egger, Matthias; Jüni, Peter

2011-01-11

To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Network meta-analysis. Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

Benzimidazole as Novel Therapy for Hormone-Refractory Metastatic Prostate Cancer

Science.gov (United States)

2011-05-01

8 4 INTRODUCTION The focus of this project is to evaluate the anti-tumor effects of benzimidazoles as a...potential anti-metastatic prostate cancer therapy. We identified benzimidazoles , a class of anti-parasitic drug, in a drug screening process for...preferential anti-tumor activity on metastatic prostate cancer cells. We have data indicate that benzimidazoles have potent anti-tumor activities

Tratamento medicamentoso da osteoartrose do joelho Drug therapy in knee osteoarthrosis

Directory of Open Access Journals (Sweden)

Márcia Uchôa de Rezende

2009-02-01

Full Text Available O tratamento clínico da osteoartrite/artrose (OA está sempre indicado e baseia-se no autocuidado feito pelo paciente e orientado pelo médico. O uso de medicamentos é complementar às medidas de emagrecimento, ganho de força, de propriocepção, de flexibilidade e de amplitude de movimento. Entre os medicamentos disponíveis para o tratamento da OA há os que são essencialmente analgésicos e que não interferem no curso da doença; bem como os anti-inflamatórios, controversos por seus efeitos colaterais e pelo seu papel na OA, porém, com propriedades analgésicas e anti-inflamatórias indiscutíveis; e, por fim, as drogas modificadoras de estrutura, que retardam a evolução da OA. As medicações ainda podem ser de uso tópico, intra-articular, oral e injetável (sistêmico. As várias apresentações de ácido hialurônico (AH mostram o poder analgésico da droga e há indícios de poder modificador de estrutura da cartilagem pela medicação. Há nível de evidência IA, para diacereína e para a glucosamina, de que retardam a evolução da OA. Mais tecnologia para diagnóstico e controle de tratamento da OA, bem como mais estudos multicêntricos são necessários para consolidar o poder do tratamento medicamentoso de outras drogas.Clinical treatment for osteoarthritis (OA is very important and is based on patient's self care and guided by the physician. Drug therapy is additional to losing weight, improving muscular strength, proprioception, flexibility and range of motion. Between the available drugs for osteoarthritis' treatment, some are basically analgesics and do not interfere on disease's progression; some are anti-inflammatory with good analgesic power but with side effects that compromise their prolonged usage; and the structure modifying drugs that slow down the progression of OA. The medications are presented in topic, oral, intra-muscular, intra-venous and intra-articular forms. The hyaluronic acid has various

The fourth national anti-tuberculosis drug resistance survey in Viet Nam.

Science.gov (United States)

Nhung, N V; Hoa, N B; Sy, D N; Hennig, C M; Dean, A S

2015-06-01

Viet Nam's Fourth National Anti-Tuberculosis Drug Resistance Survey was conducted in 2011. To determine the prevalence of resistance to the four main first-line anti-tuberculosis drugs in Viet Nam. Eighty clusters were selected using a probability proportion to size approach. Drug susceptibility testing (DST) against the four main first-line anti-tuberculosis drugs was performed. A total of 1629 smear-positive tuberculosis (TB) patients were eligible for culture. Of these, DST results were available for 1312 patients, including 1105 new TB cases, 195 previously treated TB cases and 12 cases with an unknown treatment history. The proportion of cases with resistance to any drug was 32.7% (95%CI 29.1-36.5) among new cases and 54.2% (95%CI 44.3-63.7) among previously treated cases. The proportion of multidrug-resistant TB (MDR-TB) cases was 4.0% (95%CI 2.5-5.4) in new cases and 23.3 (95%CI 16.7-29.9) in previously treated cases. The fourth drug resistance survey in Viet Nam found that the proportion of MDR-TB among new and previously treated cases was not significantly different from that in the 2005 survey. The National TB Programme should prioritise the detection and treatment of MDR-TB to reduce transmission of MDR-TB in the community.

What basal ganglia changes underlie the parkinsonian state? The significance of neuronal oscillatory activity

Science.gov (United States)

Quiroga-Varela, A.; Walters, J.R.; Brazhnik, E.; Marin, C.; Obeso, J.A.

2014-01-01

One well accepted functional feature of the parkinsonian state is the recording of enhanced beta oscillatory activity in the basal ganglia. This has been demonstrated in patients with Parkinson's disease (PD) and in animal models such as the rat with 6-hydroxydopamine (6-OHDA)-induced lesion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, all of which are associated with severe striatal dopamine depletion. Neuronal hyper-synchronization in the beta (or any other) band is not present despite the presence of bradykinetic features in the rat and monkey models, suggesting that increased beta band power may arise when nigro-striatal lesion is advanced and that it is not an essential feature of the early parkinsonian state. Similar observations and conclusions have been previously made for increased neuronal firing rate in the subthalamic and globus pallidus pars interna nuclei. Accordingly, it is suggested that early parkinsonism may be associated with dynamic changes in basal ganglia output activity leading to reduced movement facilitation that may be an earlier feature of the parkinsonian state. PMID:23727447

National anti-tuberculosis drug resistance study in Tanzania

NARCIS (Netherlands)

Chonde, T. M.; Basra, D.; Mfinanga, S. G. M.; Range, N.; Lwilla, F.; Shirima, R. P.; van Deun, A.; Zignol, M.; Cobelens, F. G.; Egwaga, S. M.; van Leth, F.

2010-01-01

OBJECTIVE: To assess the prevalence of anti-tuberculosis drug resistance in a national representative sample of tuberculosis (TB) patients in Tanzania according to recommended methodology. DESIGN: Cluster survey, with 40 clusters sampled proportional to size, of notified TB patients from all

A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

Energy Technology Data Exchange (ETDEWEB)

Li, Xiaoguang [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Department of Medical Microbiology, Harbin Medical University, Harbin 150086 (China); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Qian, Hua [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Miyamoto, Fusako [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Naito, Takeshi [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Kawaji, Kumi [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Kajiwara, Kazumi [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); JST Innovation Plaza Kyoto, Japan Science and Technology Agency, Nishigyo-ku, Kyoto 615-8245 (Japan); Hattori, Toshio [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Matsuoka, Masao [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); and others

2012-07-27

Highlights: Black-Right-Pointing-Pointer We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. Black-Right-Pointing-Pointer The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. Black-Right-Pointing-Pointer In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1{sub IIIB} and HIV-1{sub BaL} as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1{sub IIIB} activity, whereas fusion inhibitors showed both anti-HIV-1{sub IIIB} and anti-HIV-1{sub BaL} activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, 'phenotypic drug evaluation', may be applicable for the evaluation of various antiviral drugs in vivo.

A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

International Nuclear Information System (INIS)

Li, Xiaoguang; Qian, Hua; Miyamoto, Fusako; Naito, Takeshi; Kawaji, Kumi; Kajiwara, Kazumi; Hattori, Toshio; Matsuoka, Masao; Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka

2012-01-01

Highlights: ► We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. ► The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. ► In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1 IIIB and HIV-1 BaL as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1 IIIB activity, whereas fusion inhibitors showed both anti-HIV-1 IIIB and anti-HIV-1 BaL activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, “phenotypic drug evaluation”, may be applicable for the evaluation of various antiviral drugs in vivo.

Can Inhibitors of Snake Venom Phospholipases A₂ Lead to New Insights into Anti-Inflammatory Therapy in Humans? A Theoretical Study.

Science.gov (United States)

Sales, Thaís A; Marcussi, Silvana; da Cunha, Elaine F F; Kuca, Kamil; Ramalho, Teodorico C

2017-10-25

Human phospholipase A₂ ( h PLA₂) of the IIA group (HGIIA) catalyzes the hydrolysis of membrane phospholipids, producing arachidonic acid and originating potent inflammatory mediators. Therefore, molecules that can inhibit this enzyme are a source of potential anti-inflammatory drugs, with different action mechanisms of known anti-inflammatory agents. For the study and development of new anti-inflammatory drugs with this action mechanism, snake venom PLA₂ ( sv PLA₂) can be employed, since the sv PLA₂ has high similarity with the human PLA₂ HGIIA. Despite the high similarity between these secretory PLA₂s , it is still not clear if these toxins can really be employed as an experimental model to predict the interactions that occur with the human PLA₂ HGIIA and its inhibitors. Thus, the present study aims to compare and evaluate, by means of theoretical calculations, docking and molecular dynamics simulations, as well as experimental studies, the interactions of human PLA₂ HGIIA and two sv PLA₂s , Bothrops toxin II and Crotoxin B (BthTX-II and CB, respectively). Our theoretical findings corroborate experimental data and point out that the human PLA₂ HGIIA and sv PLA₂ BthTX-II lead to similar interactions with the studied compounds. From our results, the sv PLA₂ BthTX-II can be used as an experimental model for the development of anti-inflammatory drugs for therapy in humans.

Use of biomarkers in the discovery of novel anti-schizophrenia drugs

DEFF Research Database (Denmark)

Mikkelsen, Jens D; Thomsen, Morten S; Hansen, Henrik H

2010-01-01

Schizophrenia is characterized by a diverse symptomatology that often includes positive, cognitive and negative symptoms. Current anti-schizophrenic drugs act at multiple receptors, but little is known about how each of these receptors contributes to their mechanisms of action. Screening of novel...... anti-schizophrenic drug candidates targeting single receptors will be based on biomarker assays that measure signalling pathways, transcriptional factors, epigenetic mechanisms and synaptic function and translate these effects to behavioural effects in animals and humans. This review discusses current...

Anti-retroviral therapy-induced status epilepticus in "pseudo-HIV serodeconversion".

Science.gov (United States)

Etgen, Thorleif; Eberl, Bernhard; Freudenberger, Thomas

2010-01-01

Diligence in the interpretation of results is essential as information gained from the psychiatric patient's history might often be restricted. Nonobservance of established guidelines may lead to a wrong diagnosis, induce a false therapy and result in life-threatening situations. Communication errors between hospitals and doctors and uncritical acceptance of prior diagnoses add substantially to this problem. We present a patient with alcohol-related dementia who received anti-retroviral therapy that promoted a non-convulsive status epilepticus. HIV serodeconversion was considered after our laboratory result yielded a HIV-negative status. Critical review of previous diagnostic investigations revealed several errors in the diagnosis of HIV infection leading to a "pseudo-serodeconversion." Finally, anti-retroviral therapy could be discontinued. Copyright © 2010 Elsevier Inc. All rights reserved.

OFFICIAL MEDICATIONS FOR ANTI-TUMOR GENE THERAPY

Directory of Open Access Journals (Sweden)

E. R. Nemtsova

2016-01-01

Full Text Available This is a review of modern literature data of official medications for anti-tumor gene therapy as well as of medications that finished clinical trials.The article discusses the concept of gene therapy, the statistical analysis results of initiated clinical trials of gene products, the most actively developing directions of anticancer gene therapy, and the characteristics of anti-tumor gene medications.Various delivery systems for gene material are being examined, including viruses that are defective in  replication (Gendicine™ and Advexin and oncolytic (tumor specific conditionally replicating viruses (Oncorine™, ONYX-015, Imlygic®.By now three preparations for intra-tumor injection have been introduced into oncology clinical practice: two of them – Gendicine™ and Oncorine™ have been registered in China, and one of them – Imlygic® has been registered in the USA. Gendicine™ and Oncorine™ are based on the wild type p53 gene and are designed for treatment of patients with head and neck malignancies. Replicating adenovirus is the delivery system in Gendicine™, whereas oncolytic adenovirus is the vector for gene material in Oncorine™. Imlygic® is based on the  recombinant replicating HSV1 virus with an introduced GM–CSF gene and is designed for treatment of  melanoma patients. These medications are well tolerated and do not cause any serious adverse events. Gendicine™ and Oncorine™ are not effective in monotherapy but demonstrate pronounced synergism with chemoand radiation therapy. Imlygic® has just started the post marketing trials.

Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs.

Science.gov (United States)

Agrawal, Mukta; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Chougule, Mahavir Bhupal; Shoyele, Sunday A; Alexander, Amit

2018-05-23

According to the Alzheimer Association Report (2017), Alzheimer's disease (AD) is the 6th primary cause of death in the USA, which affects nearly 5.5 million people. In the year 2017 itself, the cost of AD treatment in the USA has been reported to rise to $259 billion. This statistic shows the severity of the disease in the USA which is very much similar across the globe. On the other hand, the treatment remains limited to a few conventional oral medications (approved by FDA). These are mainly acting superficially from mild to the moderate AD. The therapeutic efficacy of the drug is not only affected by its reduced concentration in the brain owing to the existence of blood-brain-barrier (BBB) but also due to its low brain permeability. In this context, the intranasal (IN) route of drug administration has emerged as an alternative route over the systemic (oral and parenteral) drug delivery to the brain. The delivery of the drug via an IN route offers various advantages over systemic drug delivery system, as it directly delivers the drug into the brain via olfactory route. Presence of drug in the olfactory bulb, in turn, increases the drug bioavailability in the brain and reduces the drug degradation as well as wastage of the drug through` systemic clearance. However, there is also some limitation associated with IN like poor drug permeation through the nasal mucosa and mucociliary clearance. The delivery system various through novel strategies (nano drug carrier system, colloidal carriers, mucoadhesive devices, controlled delivery system, pro-drug, etc.) are adapted to overcome the above-stated limitations. Although, after all, such successful research claims, very few of the nose-to-brain drug delivery of anti-AD drugs have gained market approval due to lack of sufficient clinical evidence. Onzetra Xsail® is one such marketed preparations approved for IN delivery used for the treatment of a brain disorder; migraine. In the field of patents also, no work is found

Model-based global sensitivity analysis as applied to identification of anti-cancer drug targets and biomarkers of drug resistance in the ErbB2/3 network

Science.gov (United States)

Lebedeva, Galina; Sorokin, Anatoly; Faratian, Dana; Mullen, Peter; Goltsov, Alexey; Langdon, Simon P.; Harrison, David J.; Goryanin, Igor

2012-01-01

High levels of variability in cancer-related cellular signalling networks and a lack of parameter identifiability in large-scale network models hamper translation of the results of modelling studies into the process of anti-cancer drug development. Recently global sensitivity analysis (GSA) has been recognised as a useful technique, capable of addressing the uncertainty of the model parameters and generating valid predictions on parametric sensitivities. Here we propose a novel implementation of model-based GSA specially designed to explore how multi-parametric network perturbations affect signal propagation through cancer-related networks. We use area-under-the-curve for time course of changes in phosphorylation of proteins as a characteristic for sensitivity analysis and rank network parameters with regard to their impact on the level of key cancer-related outputs, separating strong inhibitory from stimulatory effects. This allows interpretation of the results in terms which can incorporate the effects of potential anti-cancer drugs on targets and the associated biological markers of cancer. To illustrate the method we applied it to an ErbB signalling network model and explored the sensitivity profile of its key model readout, phosphorylated Akt, in the absence and presence of the ErbB2 inhibitor pertuzumab. The method successfully identified the parameters associated with elevation or suppression of Akt phosphorylation in the ErbB2/3 network. From analysis and comparison of the sensitivity profiles of pAkt in the absence and presence of targeted drugs we derived predictions of drug targets, cancer-related biomarkers and generated hypotheses for combinatorial therapy. Several key predictions have been confirmed in experiments using human ovarian carcinoma cell lines. We also compared GSA-derived predictions with the results of local sensitivity analysis and discuss the applicability of both methods. We propose that the developed GSA procedure can serve as a

Determining the Molecular Pathways Underlying the Protective Effect of Non-Steroidal Anti-Inflammatory Drugs for Alzheimer's Disease: A Bioinformatics Approach

Directory of Open Access Journals (Sweden)

Alejo J Nevado-Holgado

Full Text Available Alzheimer's disease (AD represents a substantial unmet need, due to increasing prevalence in an ageing society and the absence of a disease modifying therapy. Epidemiological evidence shows a protective effect of non steroidal anti inflammatory (NSAID drugs, and genome wide association studies (GWAS show consistent linkage to inflammatory pathways; both observations suggesting anti-inflammatory compounds might be effective in AD therapy although clinical trials to date have not been positive.In this study, we use pathway enrichment and fuzzy logic to identify pathways (KEGG database simultaneously affected in both AD and by NSAIDs (Sulindac, Piroxicam, Paracetamol, Naproxen, Nabumetone, Ketoprofen, Diclofenac and Aspirin. Gene expression signatures were derived for disease from both blood (n = 344 and post-mortem brain (n = 690, and for drugs from immortalised human cell lines exposed to drugs of interest as part of the Connectivity Map platform. Using this novel approach to combine datasets we find striking overlap between AD gene expression in blood and NSAID induced changes in KEGG pathways of Ribosome and Oxidative Phosphorylation. No overlap was found in non NSAID comparison drugs. In brain we find little such overlap, although Oxidative Phosphorylation approaches our pre-specified significance level.These findings suggest that NSAIDs might have a mode of action beyond inflammation and moreover that their therapeutic effects might be mediated in particular by alteration of Oxidative Phosphorylation and possibly the Ribosome pathway. Mining of such datasets might prove increasingly productive as they increase in size and richness. Keywords: Alzheimer's disease, NSAID, Inflammation, Fuzzy logic, Ribosome

Microencapsulation of anti-tumor, antibiotic and thrombolytic drugs in microgravity

Science.gov (United States)

Morrison, Dennis R.; Mosier, Benjamin; Cassanto, John

1994-01-01

Encapsulation of cytotoxic or labile drugs enables targeted delivery and sustained release kinetics that are not available with intravenous injection. A new liquid-liquid diffusion process has been developed for forming unique microcapsules that contain both aqueous and hydrocarbon soluble drugs. Microgravity experiments, on sounding rockets (1989-92) and Shuttle missions STS-52 (1992) and STS-56 (1993) using an automated Materials Dispersion Apparatus, produced multi-lamellar microcapsules containing both Cis-platinum (anti-tumor drug) and iodinated poppy seed oil (a radiocontrast medium), surrounded by a polyglyceride skin. Microcapsules formed with amoxicillin (antibiotic) or urokinase (a clot dissolving enzyme), co-encapsulated with IPO, are still intact after two years. Microcapsules were formed with the drug so concentrated that crystals formed inside. Multi-layered microspheres, with both hydrophobic drug compartments, can enable diffusion of complementary drugs from the same microcapsule, e.g. antibiotics and immuno-stimulants to treat resistant infections or multiple fibrinolytic drugs to dissolve emboli. Co-encapsulation of enough radio-contrast medium enables oncologists to monitor the delivery of anti-tumor microcapsules to target tumors using computerized tomography and radiography that would track the distribution of microcapsules after release from the intra-arterial catheter. These microcapsules could have important applications in chemotheraphy of certain liver, kidney, brain and other tumors.

Pharmacological therapy of spondyloarthritis.

Science.gov (United States)

Palazzi, Carlo; D'Angelo, Salvatore; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio

2015-01-01

The current pharmacological therapy of spondyloarthritis (SpA) includes several drugs: Non-steroidal anti-inflammatory drugs, corticosteroids, traditional disease-modifying antirheumatic drugs and biologic drugs. A systematic literature search was completed using the largest electronic databases (Medline, Embase and Cochrane), starting from 1995, with the aim to review data on traditional and biologic agents commercialised for SpA treatment. Randomised controlled trials and large observational studies were considered. In addition, studies performed in SpA patients treated with other, still unapproved, drugs (rituximab, anti-IL6 agents, apremilast, IL17 inhibitors and anakinra) were also taken into account. Biologic agents, especially anti-TNF drugs, have resulted in significant progress in improving clinical symptoms and signs, reducing inflammatory features in laboratory tests and imaging findings, and recovering all functional indexes. Anti-TNF drugs have radically changed the evolution of radiographic progression in peripheral joints; the first disappointing data concerning their efficacy on new bone formation of axial SpA has been recently challenged by studies enrolling patients who have been earlier diagnosed and treated. The opportunity to extend the interval of administration or to reduce the doses of anti-TNF agents can favourably influence the costs. Ustekinumab, the first non-anti-TNF biologic drug commercialised for psoriatic arthritis, offers new chances to patients that are unresponsive to anti-TNF.

Systematic comparison of drug-tolerant assays for anti-drug antibodies in a cohort of adalimumab-treated rheumatoid arthritis patients

NARCIS (Netherlands)

Bloem, Karien; van Leeuwen, Astrid; Verbeek, Gerrit; Nurmohamed, Michael T.; Wolbink, Gerrit Jan; van der Kleij, Desiree; Rispens, Theo

2015-01-01

Drug interference complicates assessment of immunogenicity of biologicals and results in an underestimation of anti-drug antibody (ADA) formation. Drug-tolerant assays have the potential to overcome such limitations. However, to which extent drug-tolerant assays provide an unbiased picture of the

Substantially Higher and Earlier Occurrence of Anti-Tuberculosis Drug-Related Adverse Reactions in HIV Coinfected Tuberculosis Patients: A Matched-Cohort Study.

Science.gov (United States)

Matono, Takashi; Nishijima, Takeshi; Teruya, Katsuji; Morino, Eriko; Takasaki, Jin; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Kaku, Mitsuo; Oka, Shinichi

2017-11-01

Little information exists on the frequency, severity, and timing of first-line anti-tuberculosis drug-related adverse events (TB-AEs) in HIV-tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.

Pathogenesis of Brain Edema and Investigation into Anti-Edema Drugs

Directory of Open Access Journals (Sweden)

Shotaro Michinaga

2015-04-01

Full Text Available Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them.

Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation.

Science.gov (United States)

Lapsia, Sameer; Koganti, Siva; Spadaro, Salvatore; Rajapakse, Ramona; Chawla, Anupama; Bhaduri-McIntosh, Sumita

2016-02-01

Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise. © 2015 Wiley Periodicals, Inc.

49 CFR 655.12 - Required elements of an anti-drug use and alcohol misuse program.

Science.gov (United States)

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Required elements of an anti-drug use and alcohol... and alcohol misuse program. An anti-drug use and alcohol misuse program shall include the following: (a) A statement describing the employer's policy on prohibited drug use and alcohol misuse in the...

Development of anti-inflammatory drugs - the research and development process.

Science.gov (United States)

Knowles, Richard Graham

2014-01-01

The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

[Anti-inflammatory, analgesic and anti-pyretic activities of a non-steroidal anti-inflammatory drug, etofenamate, in experimental animals].

Science.gov (United States)

Nakamura, H; Motoyoshi, S; Imazu, C; Ishii, K; Yokoyama, Y; Seto, Y; Kadokawa, T; Shimizu, M

1982-08-01

Anti-inflammatory, analgesic, and anti-pyretic activities of orally administered etofenamate, the diethylene glycol ester of flufenamic acid, were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice and ultra-violet light-induced erythema in guinea pigs, etofenamate produced a dose related inhibition at doses of 40--320 mg/kg and 5--20 mg/kg, respectively. In rats, felt-pellet-induced granuloma formation and adjuvant-induced arthritis were significantly inhibited by repeated administration of etofenamate at doses of 20 mg/kg/day for 5 days and 40 mg/kg/day for 21 days, respectively. Etofenamate showed an inhibitory activity on the squeak response caused by flexing and extending the silver nitrate-induced arthritic joint in rats; and it produced a dose related anti-writhing activity at doses of 50--300 mg/kg and 10--80 mg/kg in mice and rats, respectively, in the acetic acid-induced writhing test. Etofenamate showed a significant anti-pyretic activity at doses of 0.2 mg/kg or more. These potencies of etofenamate were 0.5 to 1.6 times those of flufenamic acid. In particular, the anti-erythema, anti-arthritis, and anti-pyretic activities of etofenamate were approximately equivalent to or superior to those of flufenamic acid. From these results, it was suggested that etofenamate given orally, like other non-steroidal anti-inflammatory drugs, showed anti-inflammatory, analgesic, and anti-pyretic activities in experimental animals.

Use of Fixed Dose Combination (FDC) Drugs in India: Central Regulatory Approval and Sales of FDCs Containing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Metformin, or Psychotropic Drugs

Science.gov (United States)

McGettigan, Patricia; Roderick, Peter; Mahajan, Rushikesh; Kadam, Abhay; Pollock, Allyson M.

2015-01-01

Background In 2012, an Indian parliamentary committee reported that manufacturing licenses for large numbers of fixed dose combination (FDC) drugs had been issued by state authorities without prior approval of the Central Drugs Standard Control Organization (CDSCO) in violation of rules, and considered that some ambiguity until 1 May 2002 about states’ powers might have contributed. To our knowledge, no systematic enquiry has been undertaken to determine if evidence existed to support these findings. We investigated CDSCO approvals for and availability of oral FDC drugs in four therapeutic areas: analgesia (non-steroidal anti-inflammatory drugs [NSAIDs]), diabetes (metformin), depression/anxiety (anti-depressants/benzodiazepines), and psychosis (anti-psychotics). Methods and Findings This was an ecologic study with a time-trend analysis of FDC sales volumes (2007–2012) and a cross-sectional examination of 2011–2012 data to establish the numbers of formulations on the market with and without a record of CDSCO approval (“approved” and “unapproved”), their branded products, and sales volumes. Data from the CDSCO on approved FDC formulations were compared with sales data from PharmaTrac, a database of national drug sales. We determined the proportions of FDC sales volumes (2011–2012) arising from centrally approved and unapproved formulations and from formulations including drugs banned/restricted internationally. We also determined the proportions of centrally approved and unapproved formulations marketed before and after 1 May 2002, when amendments were made to the drug rules. FDC approvals in India, the United Kingdom (UK), and United States of America (US) were compared. For NSAID FDCs, 124 formulations were marketed, of which 34 (27%) were centrally approved and 90 (73%) were unapproved; metformin: 25 formulations, 20 (80%) approved, five (20%) unapproved; anti-depressants/benzodiazepines: 16 formulations, three (19%) approved, 13 (81%) unapproved

Therapeutic Potential of Plants as Anti-Microbials for Drug Discovery

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Ramar Perumal Samy

2010-01-01

Full Text Available The uses of traditional medicinal plants for primary health care have steadily increased worldwide in recent years. Scientists are in search of new phytochemicals that could be developed as useful anti-microbials for treatment of infectious diseases. Currently, out of 80% of pharmaceuticals derived from plants, very few are now being used as anti-microbials. Plants are rich in a wide variety of secondary metabolites that have found anti-microbial properties. This review highlights the current status of traditional medicine, its contribution to modern medicine, recent trends in the evaluation of anti-microbials with a special emphasis upon some tribal medicine, in vitro and in vivo experimental design for screening, and therapeutic efficacy in safety and human clinical trails for commercial outlet. Many of these commercially available compounds are crude preparations administered without performing human clinical trials. Recent methods are useful to standardize the extraction for scientific investigation of new phytochemicals and anti-microbials of traditionally used plants. It is concluded that once the local ethnomedical preparations of traditional sources are scientifically evaluated before dispensing they should replace existing drugs commonly used for the therapeutic treatment of infection. This method should be put into practice for future investigations in the field of ethnopharmacology, phytochemistry, ethnobotany and other biological fields for drug discovery.

Pharmacokinetic aspects of the anti-epileptic drug substance vigabatrin

DEFF Research Database (Denmark)

Nøhr, Martha Kampp; Frølund, Sidsel; Holm, René

2014-01-01

are discussed in detail. Special focus is on the contribution of the proton-coupled amino acid transporter 1 (PAT1) for intestinal vigabatrin absorption. Furthermore, the review gives an overview of the pharmacokinetic parameters of vigabatrin across different species and drug-food and drug-drug interactions......Drug transporters in various tissues, such as intestine, kidney, liver and brain, are recognized as important mediators of absorption, distribution, metabolism and excretion of drug substances. This review gives a current status on the transporter(s) mediating the absorption, distribution......, metabolism and excretion properties of the anti-epileptic drug substance vigabatrin. For orally administered drugs, like vigabatrin, the absorption from the intestine is a prerequisite for the bioavailability. Therefore, transporter(s) involved in the intestinal absorption of vigabatrin in vitro and in vivo...

Photo-translocation of anti-HIV-1 drugs into TZM-bl cells

CSIR Research Space (South Africa)

Khanyile, T

2013-04-01

Full Text Available Targeted drug delivery into HIV-1 infected cells offers a reduction in toxicity and side effect. Using a femtosecond (fs) laser of different beam shapes anti-HIV-1 drugs are efficiently delivered into TZM-bl cells....

Coming to terms with nonsteroidal anti-inflammatory drug gastropathy.

Science.gov (United States)

Roth, Sanford H

2012-05-07

Despite well known complications, oral nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most commonly prescribed medications in the US for musculoskeletal disorders such as osteoarthritis. Although there has been a recent focus on the cardiovascular and renal complications associated with these agents, NSAID gastropathy continues to be a particular concern in many patients, especially those at increased risk for serious adverse events, including the elderly. Complicating the diagnosis of NSAID gastropathy is its silent course, which, up to half of the time, is asymptomatic. Several strategies are currently employed by physicians to mitigate the risk of serious gastrointestinal events. These include either addition of a proton pump inhibitor to current nonselective NSAID therapy or the use of a cyclo-oxygenase-2-selective NSAID. Although these agents are effective at mitigating the overall risk of gastrointestinal adverse events, they fail to address NSAID-related cardiovascular and renal risks. Due to their reduced systemic absorption, topical NSAIDs may present a viable option for patients at increased risk for serious NSAID-related adverse events, including gastropathy.

Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report

OpenAIRE

Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E

2011-01-01

Abstract Background The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti...

Tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous silica nanoparticle-based drug delivery system for synergetic therapy of tumor

Directory of Open Access Journals (Sweden)

Li X

2015-12-01

Full Text Available Xiaoyu Li, Meiying Wu, Limin Pan, Jianlin Shi State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4 and a chemotherapeutic drug (doxorubicin and conjugate with targeting molecules (iRGD peptide for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors. Keywords: mesoporous silica nanoparticles, drug delivery, tumor vasculatures targeting, antiangiogenic agent

Intrathecal application of autologous bone marrow cell preparations in parkinsonian syndromes

DEFF Research Database (Denmark)

Storch, Alexander; Csoti, Ilona; Eggert, Karla

2012-01-01

A growing number of patients is treated with intrathecal application of autologous bone marrow cells (aBMCs), but clinical data are completely lacking in movement disorders. We provide first clinical data on efficacy and safety of this highly experimental treatment approach in parkinsonian...

Anti-B cell antibody therapies for inflammatory rheumatic diseases

DEFF Research Database (Denmark)

Faurschou, Mikkel; Jayne, David R W

2014-01-01

Several monoclonal antibodies targeting B cells have been tested as therapeutics for inflammatory rheumatic diseases. We review important observations from randomized clinical trials regarding the efficacy and safety of anti-B cell antibody-based therapies for rheumatoid arthritis, systemic lupus...... and functions in rheumatic disorders. Future studies should also evaluate how to maintain disease control by means of conventional and/or biologic immunosuppressants after remission-induction with anti-B cell antibodies....

Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy?

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Valeria Barresi

2014-04-01

Full Text Available Despite ongoing clinical trials, the efficacy of anti-angiogenic drugs for the treatment of brain metastases (BM is still questionable. The lower response rate to anti-angiogenic therapy in the presence of BM than in metastatic disease involving other sites suggests that BM may be insensitive to these drugs, although the biological reasons underlining this phenomenon are still to be clarified. With the aim of assessing whether the targets of anti-angiogenic therapies are actually present in BM, in the present study, we analyzed the microvessel density (MVD, a measure of neo-angiogenesis, and the vascular phenotype (mature vs. immature in the tumor tissue of a series of BM derived from different primary tumors. By using immunohistochemistry against endoglin, a specific marker for newly formed vessels, we found that neo-angiogenesis widely varies in BM depending on the site of the primary tumor, as well as on its histotype. According to our results, BM from lung cancer displayed the highest MVD counts, while those from renal carcinoma had the lowest. Then, among BM from lung cancer, those from large cell and adenocarcinoma histotypes had significantly higher MVD counts than those originating from squamous cell carcinoma (p = 0.0043; p = 0.0063. Of note, MVD counts were inversely correlated with the maturation index of the endoglin-stained vessels, reflected by the coverage of smooth muscle actin (SMA positive pericytes (r = −0.693; p < 0.0001. Accordingly, all the endoglin-positive vessels in BM from pulmonary squamous cell carcinoma and renal carcinoma, displayed a mature phenotype, while vessels with an immature phenotype were found in highly vascularized BM from pulmonary large cell and adenocarcinoma. The low MVD and mature phenotype observed in BM from some primary tumors may account for their low sensitivity to anti-angiogenic therapies. Although our findings need to be validated in correlative studies with a clinical response, this should

Budget impact analysis of adjunctive therapy with lacosamide for partial-onset epileptic seizures in Belgium.

Science.gov (United States)

Simoens, Steven

2011-01-01

This study aims to compute the budget impact of lacosamide, a new adjunctive therapy for partial-onset seizures in epilepsy patients from 16 years of age who are uncontrolled and having previously used at least three anti-epileptic drugs from a Belgian healthcare payer perspective. The budget impact analysis compared the 'world with lacosamide' to the 'world without lacosamide' and calculated how a change in the mix of anti-epileptic drugs used to treat uncontrolled epilepsy would impact drug spending from 2008 to 2013. Data on the number of patients and on the market shares of anti-epileptic drugs were taken from Belgian sources and from the literature. Unit costs of anti-epileptic drugs originated from Belgian sources. The budget impact was calculated from two scenarios about the market uptake of lacosamide. The Belgian target population is expected to increase from 5333 patients in 2008 to 5522 patients in 2013. Assuming that the market share of lacosamide increases linearly over time and is taken evenly from all other anti-epileptic drugs (AEDs), the budget impact of adopting adjunctive therapy with lacosamide increases from €5249 (0.1% of reference drug budget) in 2008 to €242,700 (4.7% of reference drug budget) in 2013. Assuming that 10% of patients use standard AED therapy plus lacosamide, the budget impact of adopting adjunctive therapy with lacosamide is around €800,000-900,000 per year (or 16.7% of the reference drug budget). Adjunctive therapy with lacosamide would raise drug spending for this patient population by as much as 16.7% per year. However, this budget impact analysis did not consider the fact that lacosamide reduces costs of seizure management and withdrawal. The literature suggests that, if savings in other healthcare costs are taken into account, adjunctive therapy with lacosamide may be cost saving.

Benefit and harms of new anti-cancer drugs.

Science.gov (United States)

Vera-Badillo, Francisco E; Al-Mubarak, Mustafa; Templeton, Arnoud J; Amir, Eitan

2013-06-01

Phase III randomized controlled trials (RCTs) assess clinically important differences in endpoints that reflect benefit to and harm of patients. Defining benefit of cancer drugs can be difficult. Overall survival and quality of life are the most relevant primary endpoints, but difficulty in measuring these mean that other endpoints are often used, although their surrogacy or clinical relevance has not always been established. In general, advances in drug development have led to numerous new drugs to enter the market. Pivotal RCT of several new drugs have shown that benefit appeared greater for targeted anticancer agents than for chemotherapeutic agents. This effect seems particularly evident with targeted agents evaluated in biomarker-driven studies. Unfortunately, new therapies have also shown an increase in toxicity. Such toxicity is not always evident in the initial reports of RCTs. This may be a result of a statistical inability to detect differences between arms of RCTs, or occasionally due to biased reporting. There are several examples where reports of new toxicities could only be found in drug labels. In some cases, the small improvement in survival has come at a cost of substantial excess toxicity, leading some to consider such therapy as having equipoise.

Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone

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Carl K Edwards

2012-12-01

Full Text Available Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs or anti-TNF-α therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable" RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a DMARD and an anti-TNF-α agent (infliximab or etanercept to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N=122, unstable DMARD patients (N=18, stable DMARD patients (N=26, and stable patients on combination therapy (N=20. Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNF-α therapy. Furthermore, combination DMARD and anti-TNF-α therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

Evolving guidelines in the use of topical nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis.

Science.gov (United States)

Balmaceda, Casilda M

2014-01-21

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a standard treatment for osteoarthritis (OA), but the use of oral NSAIDs has been linked to an elevated risk for cardiovascular and gastrointestinal adverse events and renal toxicity. Topical NSAIDs are thought to afford efficacy that is comparable to oral formulations while reducing widespread systemic drug exposure, which may provide a benefit in terms of safety and tolerability. As a result, European treatment guidelines have, for many years, recommended the use of topical NSAIDs as a safe and effective treatment option for OA. Following the recent approval of several topical NSAID formulations by the US Food and Drug Administration, US treatment guidelines are increasingly recommending the use of topical NSAIDs as an alternative therapy and, in some cases, as a first-line option for OA. This commentary summarizes OA treatment guidelines that are currently available and discusses their potential evolution with regard to the increased inclusion of topical NSAIDs.

Long-term clinical effects of aspirin-desensitization therapy among patients with poorly controlled asthma and non-steroidal anti-inflammatory drug hypersensitivity: An exploratory study

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U. Förster-Ruhrmann

2015-11-01

Full Text Available Background: According to the Global Initiative for Asthma (GINA, the levels of asthma symptom control can be divided into controlled, partially controlled and uncontrolled asthma. Optional therapy for non-steroidal anti-inflammatory drugs (NSAIDs-hypersensitive asthmatics uses aspirin desensitization, but until now, this therapy is not established in difficult to treat cases. The aim of this study was to evaluate the efficacy of aspirin desensitization in patients with poorly controlled asthma. Methods: Patients with poorly controlled asthma, NDAIDs hypersensitivity and aspirin desensitization were included in the retrospective study. The data were compared to those obtained from patients with controlled asthma and aspirin therapy. Lung function, levels of asthma symptom control, asthma medication, the size of nasal polyps (NP and smell function were evaluated over 18 months. Results: Thirty-two patients were included in the study (uncontrolled/partially controlled asthma n = 12; controlled asthma n = 20. After 18 months of follow-up, the patients with poorly controlled asthma had significantly increased forced expiratory volume in 1 s (FEV1 values, as compared to the baseline (66–82%; p = 0.02, the levels of asthma control improved significantly (p  0.05 and the asthma medication was constant. In relation to nasal parameters the sense of smell improved significantly in both groups, NP-scores did not differ significantly. Conclusions: Patients with a poorly controlled asthma and NSAIDs hypersensitivity profit from an add-on aspirin therapy. Keywords: Asthma, Levels of asthma symptom control, GINA, Uncontrolled asthma, Aspirin-exacerbated respiratory disease (AERD, NSAIDs hypersensitivity, NSAIDs sensitive asthma, Nasal polyps

Progress in psoriasis therapy via novel drug delivery systems

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Nitha Vincent

2014-09-01

Full Text Available Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment.

Rapid resolution of cellulitis in patients managed with combination antibiotic and anti-inflammatory therapy.

Science.gov (United States)

Dall, Lawrence; Peterson, Sandford; Simmons, Tom; Dall, Amy

2005-03-01

There is some evidence to suggest that host inflammatory response has some effect on the clinical manifestations of cellulitis. The objective of this pilot study was to investigate whether the addition of oral nonsteroidal anti-inflammatory (NSAI) therapy to antibiotic treatment hastens resolution of cellulitis-related inflammation. Patients presenting in the emergency department with signs and symptoms of class II cellulitis were assigned to receive treatment with either antibiotic therapy alone (intravenous, supplemented with oral cephalexin or an equivalent) for 10 days (n = 33) or antibiotic therapy for 10 days plus an oral anti-inflammatory (ibuprofen 400 mg every 6 hours) for 5 days (n = 31). Patients were discharged as soon as possible to complete their therapy on an outpatient basis. The addition of an oral anti-inflammatory agent significantly (P < .05) shortened the time to regression of inflammation and complete resolution of cellulitis. Twenty-four of 29 evaluable patients (82.8%) who received supplemental anti-inflammatory treatment showed regression of inflammation within 1 to 2 days compared with only 3 of 33 patients (9.1%) treated without an anti-inflammatory in the same time frame. All patients receiving adjunctive anti-inflammatory treatment experienced complete resolution of cellulitis in 4 to 5 days or less, while 24.2% (8/33) of patients treated with antibiotic alone required 6 to 7 days, and 6.1% (2/33) required 7 days or more (P < .05). This small preliminary study provides some promising data, suggesting that the supplemental use of anti-inflammatory therapy may hasten the time to regression of inflammation and complete resolution of cellulitis.

Dopaminergic-like neurons derived from oral mucosa stem cells by developmental cues improve symptoms in the hemi-parkinsonian rat model.

Directory of Open Access Journals (Sweden)

Javier Ganz

Full Text Available Achieving safe and readily accessible sources for cell replacement therapy in Parkinson's disease (PD is still a challenging unresolved issue. Recently, a primitive neural crest stem cell population (hOMSC was isolated from the adult human oral mucosa and characterized in vitro and in vivo. In this study we assessed hOMSC ability to differentiate into dopamine-secreting cells with a neuronal-dopaminergic phenotype in vitro in response to dopaminergic developmental cues and tested their therapeutic potential in the hemi-Parkinsonian rat model. We found that hOMSC express constitutively a repertoire of neuronal and dopaminergic markers and pivotal transcription factors. Soluble developmental factors induced a reproducible neuronal-like morphology in the majority of hOMSC, downregulated stem cells markers, upregulated the expression of the neuronal and dopaminergic markers that resulted in dopamine release capabilities. Transplantation of these dopaminergic-induced hOMSC into the striatum of hemi-Parkinsonian rats improved their behavioral deficits as determined by amphetamine-induced rotational behavior, motor asymmetry and motor coordination tests. Human TH expressing cells and increased levels of dopamine in the transplanted hemispheres were observed 10 weeks after transplantation. These results demonstrate for the first time that soluble factors involved in the development of DA neurons, induced a DA phenotype in hOMSC in vitro that significantly improved the motor function of hemiparkinsonian rats. Based on their neural-related origin, their niche accessibility by minimal-invasive procedures and their propensity for DA differentiation, hOMSC emerge as an attractive tool for autologous cell replacement therapy in PD.

A qualitative assessment of the challenges of WHO prequalification for anti-malarial drugs in China.

Science.gov (United States)

Huang, Yangmu; Pan, Ke; Peng, Danlu; Stergachis, Andy

2018-04-03

While China is a major manufacturer of artemisinin and its derivatives, it lags as a global leader in terms of the total export value of anti-malarial drugs as finished pharmaceutical products ready for marketing and use by patients. This may be due to the limited number of World Health Organization (WHO) prequalified anti-malarial drugs from China. Understanding the reasons for the slow progress of WHO prequalification (PQ) in China can help improve the current situation and may lead to greater efforts in malaria eradication by Chinese manufacturers. In-depth interviews were conducted in China between November 2014 and December 2016. A total of 26 key informants from central government agencies, pharmaceutical companies, universities, and research institutes were interviewed, all of which had current or previous experience overseeing or implementing anti-malarial research and development in China. Chinese anti-malarial drugs that lack WHO PQ are mainly exported for use in the African private market. High upfront costs with unpredictable benefits, as well as limited information and limited technical support on WHO PQ, were reported as the main barriers to obtain WHO PQ for anti-malarial drugs by respondents from Chinese pharmaceutical companies. Potential incentives identified by respondents included tax relief, human resource training and consultation, as well as other incentives related to drug approval, such as China's Fast Track Channel. Government support, as well as innovative incentives and collaboration mechanisms are needed for further adoption of WHO PQ for anti-malarial drugs in China.

Monitoring of anti-cancer therapies and chemoresistance

Czech Academy of Sciences Publication Activity Database

Martinková, Jiřina; Hrabáková, Rita; Skalníková, Helena; Novák, Petr; Džubák, P.; Hajdúch, M.; Gadher, S. J.; Kovářová, Hana

2009-01-01

Roč. 6, č. 1 (2009), s. 63-63 ISSN 1109-6535. [International Conference of the Hellenic Proteomic Society /3./. 30.03.2009-01.04.2009, Nafplio] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : anti-cancer therapies Subject RIV: CE - Biochemistry

Anti-leukemic therapies induce cytogenetic changes of human bone marrow-derived mesenchymal stem cells.

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Yeh, Su-Peng; Lo, Wen-Jyi; Lin, Chiao-Lin; Liao, Yu-Min; Lin, Chen-Yuan; Bai, Li-Yuan; Liang, Ji-An; Chiu, Chang-Fang

2012-02-01

Both bone marrow hematopoietic cells (BM-HCs) and mesenchymal stem cells (BM-MSCs) may have cytogenetic aberrations in leukemic patients, and anti-leukemic therapy may induce cytogenetic remission of BM-HCs. The impact of anti-leukemic therapy on BM-MSCs remains unknown. Cytogenetic studies of BM-MSCs from 15 leukemic patients with documented cytogenetic abnormalities of BM-HCs were investigated. To see the influence of anti-leukemic therapy on BM-MSCs, cytogenetic studies were carried out in seven of them after the completion of anti-leukemic therapy, including anthracycline/Ara-C-based chemotherapy in two patients, high-dose busulfan/cyclophosphamide-based allogeneic transplantation in two patients, and total body irradiation (TBI)-based allogeneic transplantation in three patients. To simulate the effect of TBI in vitro, three BM-MSCs from one leukemic patient and two normal adults were irradiated using the same dosage and dosing schedule of TBI and cytogenetics were re-examined after irradiation. At the diagnosis of leukemia, two BM-MSCs had cytogenetic aberration, which were completely different to their BM-HCs counterpart. After the completion of anti-leukemic therapy, cytogenetic aberration was no longer detectable in one patient. Unexpectedly, BM-MSCs from three patients receiving TBI-based allogeneic transplantation acquired new, clonal cytogenetic abnormalities after transplantation. Similarly, complex cytogenetic abnormalities were found in all the three BM-MSCs exposed to in vitro irradiation. In conclusion, anti-leukemic treatments induce not only "cytogenetic remission" but also new cytogenetic abnormalities of BM-MSCs. TBI especially exerts detrimental effect on the chromosomal integrity of BM-MSCs and highlights the equal importance of investigating long-term adverse effect of anti-leukemic therapy on BM-MSCs as opposed to beneficial effect on BM-HCs.

Brain monoamine oxidase B and A in human parkinsonian dopamine deficiency disorders.

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Tong, Junchao; Rathitharan, Gausiha; Meyer, Jeffrey H; Furukawa, Yoshiaki; Ang, Lee-Cyn; Boileau, Isabelle; Guttman, Mark; Hornykiewicz, Oleh; Kish, Stephen J

2017-09-01

See Jellinger (doi:10.1093/awx190) for a scientific commentary on this article. The enzyme monoamine oxidases (B and A subtypes, encoded by MAOB and MAOA, respectively) are drug targets in the treatment of Parkinson's disease. Inhibitors of MAOB are used clinically in Parkinson's disease for symptomatic purposes whereas the potential disease-modifying effect of monoamine oxidase inhibitors is debated. As astroglial cells express high levels of MAOB, the enzyme has been proposed as a brain imaging marker of astrogliosis, a cellular process possibly involved in Parkinson's disease pathogenesis as elevation of MAOB in astrocytes might be harmful. Since brain monoamine oxidase status in Parkinson's disease is uncertain, our objective was to measure, by quantitative immunoblotting in autopsied brain homogenates, protein levels of both monoamine oxidases in three different degenerative parkinsonian disorders: Parkinson's disease (n = 11), multiple system atrophy (n = 11), and progressive supranuclear palsy (n = 16) and in matched controls (n = 16). We hypothesized that if MAOB is 'substantially' localized to astroglial cells, MAOB levels should be generally associated with standard astroglial protein measures (e.g. glial fibrillary acidic protein). MAOB levels were increased in degenerating putamen (+83%) and substantia nigra (+10%, non-significant) in multiple system atrophy; in caudate (+26%), putamen (+27%), frontal cortex (+31%) and substantia nigra (+23%) of progressive supranuclear palsy; and in frontal cortex (+33%), but not in substantia nigra of Parkinson's disease, a region we previously reported no increase in astrocyte protein markers. Although the magnitude of MAOB increase was less than those of standard astrocytic markers, significant positive correlations were observed amongst the astrocyte proteins and MAOB. Despite suggestions that MAOA (versus MAOB) is primarily responsible for metabolism of dopamine in dopamine neurons, there was no loss of the

[Development of anti-Alzheimer's disease drug based on beta-amyloid hypothesis].

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Sugimoto, Hachiro

2010-04-01

Currently, there are five anti-Alzheimer's disease drugs approved. These are tacrine, donepezil, rivastigmine, galantamine, and memantine. The mechanism of the first four drugs is acetylcholinesterase inhibition, while memantine is an NMDA-receptor antagonist. However, these drugs do not cure Alzheimer's, but are only symptomatic treatments. Therefore, a cure for Alzheimer's disease is truly needed. Alzheimer's disease is a progressive neurodegenerative disease characterized by cognitive deficits. The cause of the disease is not well understood, but research indicates that the aggregation of beta-amyloid is the fundamental cause. This theory suggests that beta-amyloid aggregation causes neurotoxicity. Therefore, development of the next anti-Alzheimer's disease drug is based on the beta-amyloid theory. We are now studying natural products, such as mulberry leaf extracts and curcumin derivatives, as potential cure for Alzheimer's disease. In this report, we describe some data about these natural products and derivatives.

Comparative Efficacy and Acceptability of Anti-TNF-Alpha Therapy in Ankylosing Spondylitis: A Mixed-Treatments Comparison

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Yehua Wang

2016-09-01

Full Text Available Background: Tumor necrosis factor α (TNFα antagonists, namely, golimumab, adalimumab, infliximab, etanercept and certolizumab have been prescribed to alleviate and treat ankylosing spondylitis (AS. However, the lack of comparative evidence does not enable us to make constructive recommendations particularly for AS patient populations. Methods: Eligible controlled trials regarding the above 5 anti-TNFα therapies were searched electronically through PubMed, Embase and Cochrane until April 1, 2015. Odds ratios (ORs were estimated and compared for efficacy (ASAS20, ASAS40, ASAS5/6 responses and ASAS partial remission and acceptability (serious adverse effects (SAE among the anti-TNFα reagents. Results: Totally, 25 trials with 2989 participants were incorporated in this mixed treatment comparison. All the 5 TNFα blockers achieved better ASAS20, ASAS40, ASAS5/6 and ASAS-PR responses than the placebo. Furthermore, there was no significant distinction existed among inter-drug comparisons, except that unfavorable effects induced by certolizumab seemed to be less severe than those by etanercept (OR = 0.22, 95% CI: 0.05-0.93. Apart from that, etanercept was estimated to arrive at the most favorable ASAS20 response (90.6% and SAE (83.6%, while infliximab seemed to accomplish the best ASAS40 (83.6% and ASAS-PR responses (77.3%. In addition, adalimumab was estimated to rank the highest ASAS5/6 response (75.0%. Conclusions: Etanercept, infliximab and adalimumab might be prioritized among the commonly recognized 5 anti-TNFα therapies specific for AS patients, though existing evidence did not suffice to confirm significant superiority among the above 5 anti-TNFα reagent.

[Drug eruptions caused by noncorticoid anti-inflammatory agents].

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Roujeau, J C; Guillaume, J C; Revuz, J; Touraine, R

1984-01-01

Non-steroidal anti-inflammatory drugs (NSAI) may elicit various kinds of cutaneous side effects. The commonest ones are non-specific erythematous eruptions, sometimes with a phototoxic distribution, and urticaria. Vasculitis and severe bullous eruptions (Stevens-Johnson's syndrome and Toxic Epidermal Necrolysis) are rare but may have severe outcomes. The overall incidence of cutaneous reactions is about the same for all NSAI, 1 to 3 p. 100, during the clinical studies performed before marketing the drug, but this increases afterwards (up to 45 p. 100 for Benoxaprofen). Drugs with long half-lives may carry a higher risk for severe cutaneous reactions. NSAI are now the main cause of drug induced TEN. Urticarial reactions seem related to pharmacological phenomena while the pathogenic events leading to other kinds of skin reactions remain unknown. An hypersensitivity reaction is postulated. The therapeutic value of corticosteroids for the severe cutaneous side effects of drugs is still controversial.

Anti-TNF-alpha therapy for sight threatening uveitis.

NARCIS (Netherlands)

E.W. Lindstedt (Eric); G.S. Baarsma (Seerp); R.W.A.M. Kuijpers (Robert); P.M. van Hagen (Martin)

2005-01-01

textabstractAIM: To describe the effect of additional treatment with anti-TNF-alpha therapy in a case series of 13 patients with serious sight threatening uveitis. METHODS: 13 patients with serious sight threatening uveitis were included, of whom six had Behcet's disease, five had idiopathic

Using microgravity for defining novel anti-atherosclerotic therapy

NARCIS (Netherlands)

Verhaar, A; Krishnadath, KK; Peppelenbosch, MP

2005-01-01

Among the most important insights into coronary and inflammatory disease is that the formation of vessel occluding placques is its essence an inflammatory process, that is counteracted by anti-inflammatory drugs Current therapeutical options of dealing with the increased challenge to public health

Optimization of anti-cancer drugs and a targeting molecule on multifunctional gold nanoparticles

International Nuclear Information System (INIS)

Rizk, Nahla; Christoforou, Nicolas; Lee, Sungmun

2016-01-01

Breast cancer is the most common and deadly cancer among women worldwide. Currently, nanotechnology-based drug delivery systems are useful for cancer treatment; however, strategic planning is critical in order to enhance the anti-cancer properties and reduce the side effects of cancer therapy. Here, we designed multifunctional gold nanoparticles (AuNPs) conjugated with two anti-cancer drugs, TGF-β1 antibody and methotrexate, and a cancer-targeting molecule, folic acid. First, optimum size and shape of AuNPs was selected by the highest uptake of AuNPs by MDA-MB-231, a metastatic human breast cancer cell line. It was 100 nm spherical AuNPs (S-AuNPs) that were used for further studies. A fixed amount (900 μl) of S-AuNP (3.8 × 10"8 particles/ml) was conjugated with folic acid-BSA or methotrexate-BSA. Methotrexate on S-AuNP induced cellular toxicity and the optimum amount of methotrexate-BSA (2.83 mM) was 500 μl. Uptake of S-AuNPs was enhanced by folate conjugation that binds to folate receptors overexpressed by MDA-MB-231 and the optimum uptake was at 500 μl of folic acid-BSA (2.83 mM). TGF-β1 antibody on S-AuNP reduced extracellular TGF-β1 of cancer cells by 30%. Due to their efficacy and tunable properties, we anticipate numerous clinical applications of multifunctional gold nanospheres in treating breast cancer. (paper)

Optimization of anti-cancer drugs and a targeting molecule on multifunctional gold nanoparticles

Science.gov (United States)

Rizk, Nahla; Christoforou, Nicolas; Lee, Sungmun

2016-05-01

Breast cancer is the most common and deadly cancer among women worldwide. Currently, nanotechnology-based drug delivery systems are useful for cancer treatment; however, strategic planning is critical in order to enhance the anti-cancer properties and reduce the side effects of cancer therapy. Here, we designed multifunctional gold nanoparticles (AuNPs) conjugated with two anti-cancer drugs, TGF-β1 antibody and methotrexate, and a cancer-targeting molecule, folic acid. First, optimum size and shape of AuNPs was selected by the highest uptake of AuNPs by MDA-MB-231, a metastatic human breast cancer cell line. It was 100 nm spherical AuNPs (S-AuNPs) that were used for further studies. A fixed amount (900 μl) of S-AuNP (3.8 × 108 particles/ml) was conjugated with folic acid-BSA or methotrexate-BSA. Methotrexate on S-AuNP induced cellular toxicity and the optimum amount of methotrexate-BSA (2.83 mM) was 500 μl. Uptake of S-AuNPs was enhanced by folate conjugation that binds to folate receptors overexpressed by MDA-MB-231 and the optimum uptake was at 500 μl of folic acid-BSA (2.83 mM). TGF-β1 antibody on S-AuNP reduced extracellular TGF-β1 of cancer cells by 30%. Due to their efficacy and tunable properties, we anticipate numerous clinical applications of multifunctional gold nanospheres in treating breast cancer.

Smoking, caffeine, and nonsteroidal anti-inflammatory drugs in families with Parkinson disease.

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Hancock, Dana B; Martin, Eden R; Stajich, Jeffrey M; Jewett, Rita; Stacy, Mark A; Scott, Burton L; Vance, Jeffery M; Scott, William K

2007-04-01

To assess associations between Parkinson disease (PD) and putatively protective factors-smoking, caffeine (coffee, tea, and soft drinks), and nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, and naproxen). Family-based case-control study. Academic medical center clinic. A total of 356 case subjects and 317 family controls who self-reported environmental exposures. Associations between PD and environmental measures (history, status, dosage, duration, and intensity) of smoking, coffee, caffeine, nonsteroidal anti-inflammatory drugs, and non-aspirin nonsteroidal anti-inflammatory drugs were examined using generalized estimating equations with an independent correlation matrix while controlling for age and sex. Individuals with PD were significantly less likely to report ever smoking (odds ratio = 0.56; 95% confidence interval, 0.41-0.78). Additional measures of smoking revealed significant inverse associations with PD (Pcoffee drinking was inversely associated with PD (test for trend P = .05). Increasing dosage (trend P = .009) and intensity (trend P = .01) of total caffeine consumption were also inversely associated, with high dosage presenting a significant inverse association for PD (odds ratio = 0.58; 95% confidence interval, 0.34-0.99). There were no significant associations between nonsteroidal anti-inflammatory drugs and PD. Inverse associations of smoking and caffeine were corroborated using families with PD, thus emphasizing smoking and caffeine as important covariates to consider in genetic studies of PD.

Laboratory markers in personalized drug therapy

NARCIS (Netherlands)

Geerts, A.F.J.

2012-01-01

During the last decade two major trends have influenced the thinking about the benefit-risk balance in drug therapy.The first trend showed that this balance is not only determined by the interaction of the pharmacological properties of the drug with the patient’s (patho)physiological profile, but is

Pharmacogenetic & pharmacokinetic biomarker for efavirenz based ARV and rifampicin based anti-TB drug induced liver injury in TB-HIV infected patients.

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Getnet Yimer

Full Text Available BACKGROUND: Implication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury (DILI has not been yet studied. We performed a prospective case-control association study to identify the incidence, pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury (DILI in HIV and tuberculosis (TB co-infected patients. METHODS AND FINDINGS: Newly diagnosed treatment naïve TB-HIV co-infected patients (n = 353 were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy, and assessed clinically and biochemically for DILI up to 56 weeks. Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 genes were done. The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant association of DILI with being of the female sex (p = 0.001, higher plasma efavirenz level (p = 0.009, efavirenz/8-hydroxyefavirenz ratio (p = 0.036, baseline AST (p = 0.022, ALT (p = 0.014, lower hemoglobin (p = 0.008, and serum albumin (p = 0.007, NAT2 slow-acetylator genotype (p = 0.039 and ABCB1 3435TT genotype (p = 0.001. CONCLUSION: We report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients. Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients. Close monitoring of plasma efavirenz level and liver enzymes during early therapy and/or genotyping practice in HIV clinics is recommended for early identification

Development of facile drug delivery platform of ranibizumab fabricated PLGA-PEGylated magnetic nanoparticles for age-related macular degeneration therapy.

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Yan, Jian; Peng, Xifeng; Cai, Yulian; Cong, Wendong

2018-06-01

The present anti-angiogenic therapies for neovascular age-related macular degeneration require effective drug delivery systems for transfer drug molecules. Ranibizumab is an active humanized monoclonal antibody that counteracts active forms of vascular endothelial growth factor A in the neovascular age-related macular degeneration therapy. The development of ranibizumab-related therapies, we have designed the effective drug career with engineered magnetic nanoparticles (Fe 3 O 4 ) as a facile platform of ranibizumab delivery for the treatment of neovascular age-related macular degeneration. Ranibizumab conjugated iron oxide (Fe 3 O 4 )/PEGylated poly lactide-co-glycolide (PEG-PLGA) was successfully designed and the synthesized materials are analyzed different analytical techniques. The microscopic techniques (Scanning Electron Microscopy (SEM) & Transmission Electron Microscopy (TEM)) are clearly displayed that spherical nanoparticles into the PEG-PLGA matrix and presence of elements and chemical interactions confirmed by the results of energy dispersive X-ray analysis (EDX) and Fourier trans-form infrared (FTIR) spectroscopic methods. The in vitro anti-angiogenic evaluation of Fe 3 O 4 /PEG-PLGA polymer nanomaterial efficiently inhibits the tube formation in the Matrigel-based assay method by using human umbilical vein endothelial cells. Ranibizumab treated Fe 3 O 4 /PEG-PLGA polymer nanomaterials not disturbed cell proliferation and the results could not display the any significant differences in human endothelial cells. The present investigated results describe that Fe 3 O 4 /PEG-PLGA polymer nanomaterials can be highly favorable and novel formulation for the treatment of neovascular age-related macular degeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention.

NARCIS (Netherlands)

Vonkeman, Harald Erwin; van de Laar, Mart A F J

2010-01-01

Objectives: To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of action, toxicities, strategies for the prevention of toxicity, and future developments. - Methods: Medline search for articles published up to 2007, using the keywords acetylsalicylic acid,

Nanotech revolution for the anti-cancer drug delivery through blood-brain barrier.

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Caraglia, M; De Rosa, G; Salzano, G; Santini, D; Lamberti, M; Sperlongano, P; Lombardi, A; Abbruzzese, A; Addeo, R

2012-03-01

Nanotechnology-based drug delivery was born as a chance for pharmaceutical weapons to be delivered in the body sites where drug action is required. Specifically, the incorporation of anti-cancer agents in nanodevices of 100-300 nm allows their delivery in tissues that have a fenestrated vasculature and a reduced lymphatic drainage. These two features are typical of neoplastic tissues and, therefore, allow the accumulation of nanostructured devices in tumours. An important issue of anti-cancer pharmacological strategies is the overcoming of anatomical barriers such as the bloodbrain- barrier (BBB) that protects brain from toxicological injuries but, at the same time, makes impossible for most of the pharmacological agents with anti-cancer activity to reach tumour cells placed in the brain and derived from either primary tumours or metastases. In fact, only highly lipophilic molecules can passively diffuse through BBB to reach central nervous system (CNS). Another possibility is to use nanotechnological approaches as powerful tools to across BBB, by both prolonging the plasma half-life of the drugs and crossing fenestrations of BBB damaged by brain metastases. Moreover, modifications of nanocarrier surface with specific endogenous or exogenous ligands can promote the crossing of intact BBB as in the case of primary brain tumours. This aim can be achieved through the binding of the nanodevices to carriers or receptors expressed by the endothelial cells of BBB and that can favour the internalization of the nanostructured devices delivering anti-cancer drugs. This review summarizes the most meaningful advances in the field of nanotechnologies for brain delivery of drugs.

Multicentre European study of thalamic stimulation in parkinsonian and essential tremor

NARCIS (Netherlands)

Limousin, P.; Speelman, J. D.; Gielen, F.; Janssens, M.

1999-01-01

Thalamic stimulation has been proposed to treat disabling tremor. The aims of this multicentre study were to evaluate the efficacy and the morbidity of thalamic stimulation in a large number of patients with parkinsonian or essential tremor. One hundred and eleven patients were included in the study

Nonsteroidal anti-inflammatory drugs for treatment of acute gout

NARCIS (Netherlands)

van Durme, Caroline M. P. G.; Wechalekar, Mihir D.; Landewé, Robert B. M.

2015-01-01

Are nonsteroidal anti-inflammatory drugs (NSAIDs) associated with better outcomes than cyclooxygenase inhibitors, glucocorticoids, IL-1 inhibitors or placebo in the treatment of acute gout? NSAIDs are not significantly associated with a difference in pain reduction compared with cyclooxygenase

In silico approaches and chemical space of anti-P-type ATPase compounds for discovering new antituberculous drugs.

Science.gov (United States)

Santos, Paola; López-Vallejo, Fabian; Soto, Carlos-Y

2017-08-01

Tuberculosis (TB) is one of the most important public health problems around the world. The emergence of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains has driven the finding of alternative anti-TB targets. In this context, P-type ATPases are interesting therapeutic targets due to their key role in ion homeostasis across the plasma membrane and the mycobacterial survival inside macrophages. In this review, in silico and experimental strategies used for the rational design of new anti-TB drugs are presented; in addition, the chemical space distribution based on the structure and molecular properties of compounds with anti-TB and anti-P-type ATPase activity is discussed. The chemical space distribution compared to public compound libraries demonstrates that natural product libraries are a source of novel chemical scaffolds with potential anti-P-type ATPase activity. Furthermore, compounds that experimentally display anti-P-type ATPase activity belong to a chemical space of molecular properties comparable to that occupied by those approved for oral use, suggesting that these kinds of molecules have a good pharmacokinetic profile (drug-like) for evaluation as potential anti-TB drugs. © 2017 John Wiley & Sons A/S.

Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex.

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Li, Qian; Ke, Ya; Chan, Danny C W; Qian, Zhong-Ming; Yung, Ken K L; Ko, Ho; Arbuthnott, Gordon W; Yung, Wing-Ho

2012-12-06

Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents. Copyright © 2012 Elsevier Inc. All rights reserved.

Research progress in antiviral therapy for chronic hepatitis C

Directory of Open Access Journals (Sweden)

YU Guoying

2015-04-01

Full Text Available Antiviral therapy is the most important treatment for chronic hepatitis C. This paper reviews the progress in antiviral treatment over recent years, including the combination therapy with polyethylene glycol-Interferon (PEG-IFN and ribavirin (RBV, specific target therapy, and gene therapy. The paper believes that the anti-hepatitis C virus treatment needs more effective drug combination therapies, shorter courses, less side effect, higher drug resistance threshold, etc.

Colloidal silver nanoparticles improve anti-leukemic drug efficacy via amplification of oxidative stress.

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Guo, Dawei; Zhang, Junren; Huang, Zhihai; Jiang, Shanxiang; Gu, Ning

2015-02-01

Recently, increased reactive oxygen species (ROS) levels and altered redox status in cancer cells have become a novel therapeutic strategy to improve cancer selectivity over normal cells. It has been known that silver nanoparticles (AgNPs) display anti-leukemic activity via ROS overproduction. Hence, we hypothesized that AgNPs could improve therapeutic efficacy of ROS-generating agents against leukemia cells. In the current study, N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, was used as a drug model of ROS induction to investigate its synergistic effect with AgNPs. The data exhibited that AgNPs with uniform size prepared by an electrochemical method could localize in the lysosomes, mitochondria and cytoplasm of SHI-1 cells. More importantly, AgNPs together with 4-HPR could exhibit more cytotoxicity and apoptosis via overproduction of ROS in comparison with that alone. Taken together, these results reveal that AgNPs combined with ROS-generating drugs could potentially enhance therapeutic efficacy against leukemia cells, thereby providing a novel strategy for AgNPs in leukemia therapy. Copyright © 2015. Published by Elsevier B.V.

[Effect of anti-inflammatory therapy on the treatment of dry eye syndrome].

Science.gov (United States)

Mrukwa-Kominek, Ewa; Rogowska-Godela, Anna; Gierek-Ciaciura, Stanisława

2007-01-01

Dry eye syndrome is a common chronic disease; agents and strategies for its effective management are still lacking. The syndrome tends to be accompanied by ocular surface inflammation; therefore, the use of anti-inflammatory agents might prove beneficial. The authors present up-to-date guidelines, strategies, and efficacy of dry eye syndrome management, including anti-inflammatory treatment. As no diagnostic tests are now available to assess ocular surface inflammation severity, the right timing to launch an anti-inflammatory agent is difficult to determine. Patients with mild intermittent bouts of symptoms which can be alleviated with ophthalmic lubricants do not typically require anti-inflammatory therapy. The latter should be considered in those who do not respond to lubricating drops, obtain poor results on clinical tests, and show symptoms of ocular surface irritation (eg. conjunctivae redness). Anti-inflammatory treatment of dry eye syndrome may include short-term corticosteroids, cyclosporine A emulsion, oral tetracycline therapy, oral omega-3 fatty acid supplements, and autologous serum eye drops. Anti-inflammatory treatment should be safe and effective; potential benefits should be evaluated for each individual patient. The authors have reviewed the advantages of anti-inflammatory treatment in dry eye syndrome, presented in literature.

Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs

Science.gov (United States)

Ogundeji, Adepemi O.; Pohl, Carolina H.

2016-01-01

The usage of fluconazole and amphotericin B in clinical settings is often limited by, among other things, drug resistance development and undesired side effects. Thus, there is a constant need to find new drugs to better manage fungal infections. Toward this end, the study described in this paper considered the repurposing of aspirin (acetylsalicylic acid) and ibuprofen as alternative drugs to control the growth of cryptococcal cells. In vitro susceptibility tests, including a checkerboard assay, were performed to assess the response of Cryptococcus neoformans and Cryptococcus gattii to the above-mentioned anti-inflammatory drugs. Next, the capacity of these two drugs to induce stress as well as their mode of action in the killing of cryptococcal cells was determined. The studied fungal strains revealed a response to both aspirin and ibuprofen that was dose dependent, with ibuprofen exerting greater antimicrobial action. More importantly, the MICs of these drugs did not negatively (i) affect growth or (ii) impair the functioning of macrophages; rather, they enhanced the ability of these immune cells to phagocytose cryptococcal cells. Ibuprofen was also shown to act in synergy with fluconazole and amphotericin B. The treatment of cryptococcal cells with aspirin or ibuprofen led to stress induction via activation of the high-osmolarity glycerol (HOG) pathway, and cell death was eventually achieved through reactive oxygen species (ROS)-mediated membrane damage. The presented data highlight the potential clinical application of aspirin and ibuprofen as candidate anti-Cryptococcus drugs. PMID:27246782

Anti-TNFα therapy for chronic inflammatory disease in kidney transplant recipients: Clinical outcomes.

Science.gov (United States)

Garrouste, Cyril; Anglicheau, Dany; Kamar, Nassim; Bachelier, Claire; Rivalan, Joseph; Pereira, Bruno; Caillard, Sophie; Aniort, Julien; Gatault, Philippe; Soubrier, Martin; Sayegh, Johnny; Colosio, Charlotte; Buisson, Anthony; Thervet, Eric; Bouvier, Nicolas; Heng, Anne Elisabeth

2016-10-01

Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34-51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1).Anti-TNFα therapies resulted in a clinical response in 13/16 patients (81%). Estimated glomerular filtration rates (MDRD-4) were similar on day 0 and at 24 months (M24) after anti-TNFα treatment had been initiated (41 [12-55] and 40 [21-53] mL/min/1.73 m, respectively). Two allograft losses were observed. The 1st case was due to antibody-mediated rejection (M18), while the 2nd was the result of AA amyloidosis recurrence (M20). There were several complications: 8 patients (50%) developed 23 serious infections (18 bacterial, 4 viral, and 1 fungal) and 4 developed cancer. Five patients died (infection n = 2, cardiac AA amyloidosis n = 1, intraalveolar hemorrhage following microscopic polyangiitis n = 1, and acute respiratory distress syndrome n = 1). On univariate analysis, recipient age associated with death (P = 0.009) and infection development (P = 0.06).Using anti-TNFα therapies, remission can be achieved in chronic inflammatory diseases in kidney-transplant patients. However, concommitant anti-TNFα and immunosuppresive therapies must be used with caution due to the high risk of infection, particularly after the age of 50.

Drug immunogenicity in patients with inflammatory arthritis and secondary failure to tumour necrosis factor inhibitor therapies: the REASON study.

Science.gov (United States)

Balsa, Alejandro; Sanmarti, Raimon; Rosas, José; Martin, Victor; Cabez, Ana; Gómez, Susana; Montoro, María

2018-04-01

The aims were to evaluate the prevalence of anti-drug antibodies (ADA) in patients with RA or SpA experiencing secondary failure to anti-TNF therapy and to correlate ADA presence with anti-TNF concentration and clinical response. This was a cross-sectional, observational study of patients with active RA or SpA experiencing secondary failure to etanercept (ETN), infliximab (INF) or adalimumab (ADL). Concomitant non-biologic DMARDs were permitted. Serum anti-TNF and ADA levels were measured with two-site ELISA. Among 570 evaluable patients, those with RA (n = 276) were mostly female (80 vs 39%), older (56 vs 48 years), received concomitant DMARDs (83 vs 47%) and had maintained good clinical disease control for longer (202 vs 170 weeks) compared with patients with SpA (n = 294). ADA were found in 114/570 (20.0%) patients; 51/188 (27.1%) against INF and 63/217 (29.0%) against ADL; none against ETN. Of these 114 patients, 92 (81%) had no detectable serum drug concentrations. Proportionately more patients with SpA (31.3%) had anti-INF antibodies than those with RA (21.1%; P = 0.014). A significantly lower proportion of patients receiving concomitant DMARDs (16.5%) developed ADA than those on monotherapy (26.4%; P reasons for secondary treatment failure, but not the only one. Further investigations are needed to determine other causes of anti-TNF failure.

Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

Directory of Open Access Journals (Sweden)

Vibeke Andersen

2017-03-01

Full Text Available We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD, to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51. A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively. In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in prospective observational, animal and interventional studies are warranted.

Spiritual self-schema therapy, drug abuse, and HIV.

Science.gov (United States)

Marcotte, David; Avants, S Kelly; Margolin, Arthur

2003-01-01

This case report describes the use of Spiritual Self-Schema (3-S) therapy in the treatment of an HIV-positive inner-city drug user maintained on methadone and referred for additional treatment due to unremitting cocaine use. 3-S therapy is a manual-guided intervention based on cognitive self-schema theory. Its goal is to help the patient create, elaborate, and make accessible a cognitive schema--the "spiritual" self-schema-that is incompatible with drug use and other HIV risk behaviors. 3-S therapy facilitates a cognitive shift from the habitual activation of the "addict" self-schema, with its drug-related cognitions, scripts and action plans, to the "spiritual" self-schema, with its associated repertoire of harm reduction beliefs and behaviors.

Quality of Life in Arthritis Patients Using Nonsteroidal Anti-Inflammatory Drugs

Directory of Open Access Journals (Sweden)

Ingela Wiklund

1999-01-01

Full Text Available Arthritis is a painful and disabling condition. To suppress the pain and the inflammatory process, patients are often chronic nonsteroidal anti-inflammatory drug (NSAID users. Chronic use of NSAIDs may induce peptic ulcer, dyspeptic problems and heartburn. Therefore, these patients are often provided with treatment to relieve and/or protect against gastrointestinal problems. Rheumatic disorders also affect a range of health-related quality of life domains. In one study, patients with NSAID-associated gastroduodenal lesions complained about lack of energy, sleep disturbances, emotional distress and social isolation in addition to pain and mobility limitations. The degree of distress and dysfunction differed markedly from scores in an unselected population. Clinical trial data suggest that acid-suppressing therapy with omeprazole is superior to therapy with misoprostol and ranitidine in healing gastroduodenal lesions and preventing abdominal pain, heartburn and indigestion symptoms during continued NSAID treatment. Because arthritic patients are severely incapacitated by their condition regarding most aspects of health-related quality of life, it is important to offer a treatment that is effective in healing and preventing NSAID-induced ulcers and gastrointestinal symptoms during continued NSAID treatment without further compromising the patients’ quality of life. Treatment with omeprazole once daily has been shown to be superior to that with ranitidine and misoprostol in this respect.

Two-year survival rates of anti-TNF-α therapy in psoriatic arthritis (PsA) patients with either polyarticular or oligoarticular PsA.

Science.gov (United States)

Iannone, F; Lopriore, S; Bucci, R; Scioscia, C; Anelli, M G; Notarnicola, A; Lapadula, G

2015-05-01

To evaluate the 2-year drug survival rates of the tumour necrosis factor (TNF)-α blockers adalimumab, etanercept, and infliximab in psoriatic arthritis (PsA) patients with either oligoarticular (oligo-PsA) or polyarticular PsA (poly-PsA). We studied a prospective cohort of 328 PsA patients with peripheral arthritis (213 with poly-PsA and 115 with oligo-PsA), beginning their first ever anti-TNF-α treatment with adalimumab, etanercept, or infliximab. The aim of the study was to evaluate the drug survival rates and possible baseline predictors at 2 years. After 24 months, persistence in therapy with the first anti-TNF-α blocker was not statistically different in the oligo-PsA (70.4%) and poly-PsA (65.7%) subsets. Predictors of drug discontinuation were female sex [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.00-2.68, p = 0.04] and starting the therapy in years 2003-8 (HR 0.51, 95% CI 0.33-0.80, p = 0.003). In poly-PsA, the persistence of etanercept (68.3%) was significantly higher than that of adalimumab (51.9%, p = 0.01), whereas in oligo-PsA no significant difference was detected. In poly-PsA, the period 2003-8 was a negative predictor (HR 0.36, 95% CI 0.21-0.62, p = 0.0001) whereas in oligo-PsA female gender was a positive predictor of drug discontinuation (HR 2.08, 95% CI 1.02-4.24, p = 0.04). With regard to clinical outcomes, the best responses in terms of European League Against Rheumatism (EULAR) 'good' response or Disease Activity Score (DAS28) remission, crude or adjusted according to the LUND Efficacy indeX (LUNDEX), were seen in patients on etanercept or infliximab. Our study provides some evidence that anti-TNF-α drugs may perform differently in PsA, and that the analysis of clinical disease subsets may improve our knowledge and promote better management of PsA.

Nanomedicine of synergistic drug combinations for cancer therapy - Strategies and perspectives.

Science.gov (United States)

Zhang, Rui Xue; Wong, Ho Lun; Xue, Hui Yi; Eoh, June Young; Wu, Xiao Yu

2016-10-28

Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Accuracy of Consecutive Fecal Calprotectin Measurements to Predict Relapse in Inflammatory Bowel Disease Patients Under Maintenance With Anti-TNF Therapy: A Prospective Longitudinal Cohort Study.

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Ferreiro-Iglesias, Rocio; Barreiro-de Acosta, Manuel; Lorenzo-Gonzalez, Aurelio; Dominguez-Muñoz, Juan E

2018-03-01

Predicting relapse in inflammatory bowel disease (IBD) patients could allow early changes in therapy. We aimed at evaluating the accuracy of consecutive fecal calprotectin (FC) measurements to predict flares in IBD patients under maintenance treatment with anti-tumor necrosis factor (TNF) drugs. A prospective longitudinal cohort study with 16-month follow-up period was designed. IBD patients in clinical remission for at least 6 months under anti-TNF therapy were included. FC was quantified at 4-month intervals for 1 year, and patients were clinically evaluated for relapse at 2-month intervals. Diagnostic accuracy of FC for predicting relapse was evaluated by receiver-operating characteristic curve analysis. In total, 95 of 106 included patients finalized the study and were analyzed (median age 44 y, 50.5% female, 75% with Crohn's disease). A total of 30 patients (31.6%) had a relapse over follow-up. FC concentration was significantly higher in patients who relapsed (477 μg/g) than in patients who maintained in remission (65 μg/g) (Ppredict remission was 130 μg/g (negative predictive value of 100%), and 300 μg/g to predict relapse (positive predictive value of 78.3%). FC is a good predictor of clinical relapse and a particularly good predictor of remission over the following 4 months in patients with IBD on maintenance therapy with anti-TNF drugs. FC levels 300 μg/g allow predicting relapse with a high probability at any time over the following 4 months.

Effects of music therapy on drug therapy of adult psychiatric outpatients: A pilot randomised controlled study

Directory of Open Access Journals (Sweden)

Mario Degli Stefani

2016-10-01

Full Text Available Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in the treatment of psychiatric outpatients. Method: Participants (n = 27 with ICD-10 diagnoses of F20 (schizophrenia, F25 (schizoaffective disorders, F31 (bipolar affective disorder, F32 (depressive episode and F60 (specific personality disorders were randomised to receive group music therapy plus standard care (48 weekly sessions of two hours or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilisers and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage relative to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilisers did not show any significant change in either group. Conclusions: Group music therapy combined with standard drug care is effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discuss the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centred perspective were also discussed.

Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study

Science.gov (United States)

Degli Stefani, Mario; Biasutti, Michele

2016-01-01

Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants (n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed. PMID:27774073

International comparison of the factors influencing reimbursement of targeted anti-cancer drugs.

Science.gov (United States)

Lim, Carol Sunghye; Lee, Yun-Gyoo; Koh, Youngil; Heo, Dae Seog

2014-11-29

Reimbursement policies for anti-cancer drugs vary among countries even though they rely on the same clinical evidence. We compared the pattern of publicly funded drug programs and analyzed major factors influencing the differences. We investigated reimbursement policies for 19 indications with targeted anti-cancer drugs that are used variably across ten countries. The available incremental cost-effectiveness ratio (ICER) data were retrieved for each indication. Based on the comparison between actual reimbursement decisions and the ICERs, we formulated a reimbursement adequacy index (RAI): calculating the proportion of cost-effective decisions, either reimbursement of cost-effective indications or non-reimbursement of cost-ineffective indications, out of the total number of indications for each country. The relationship between RAI and other indices were analyzed, including governmental dependency on health technology assessment, as well as other parameters for health expenditure. All the data used in this study were gathered from sources publicly available online. Japan and France were the most likely to reimburse indications (16/19), whereas Sweden and the United Kingdom were the least likely to reimburse them (5/19 and 6/19, respectively). Indications with high cost-effectiveness values were more likely to be reimbursed (ρ = -0.68, P = 0.001). The three countries with high RAI scores each had a healthcare system that was financed by general taxation. Although reimbursement policies for anti-cancer drugs vary among countries, we found a strong correlation of reimbursements for those indications with lower ICERs. Countries with healthcare systems financed by general taxation demonstrated greater cost-effectiveness as evidenced by reimbursement decisions of anti-cancer drugs.

Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-κB inhibitors in ovarian cancer therapy.

Directory of Open Access Journals (Sweden)

Luiz F Zerbini

Full Text Available Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24 is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer.

Covalent linkage of nanodiamond-paclitaxel for drug delivery and cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Liu, Kuang-Kai; Wang, Chi-Ching; Chao, Jui-I [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30013, Taiwan (China); Zheng, Wen-Wei; Lo, Yu-Shiu; Chen, Chinpiao [Department of Chemistry, National Dong Hwa University, Hualien 97401, Taiwan (China); Chiu, Yu-Chung; Cheng, Chia-Liang, E-mail: clcheng@mail.ndhu.edu.tw, E-mail: chinpiao@mail.ndhu.edu.tw, E-mail: jichao@faculty.nctu.edu.tw [Department of Physics, National Dong Hwa University, Hualien 97401, Taiwan (China)

2010-08-06

A nanoparticle-conjugated cancer drug provides a novel strategy for cancer therapy. In this study, we manipulated nanodiamond (ND), a carbon nanomaterial, to covalently link paclitaxel for cancer drug delivery and therapy. Paclitaxel was bound to the surface of 3-5 nm sized ND through a succession of chemical modifications. The ND-paclitaxel conjugation was measured by atomic force microscope and nuclear magnetic resonance spectroscopy, and confirmed with infrared spectroscopy by the detection of deuterated paclitaxel. Treatment with 0.1-50 {mu}g ml{sup -1} ND-paclitaxel for 48 h significantly reduced the cell viability in the A549 human lung carcinoma cells. ND-paclitaxel induced both mitotic arrest and apoptosis in A549 cells. However, ND alone or denatured ND-paclitaxel (after treatment with strong alkaline solution, 1 M NaOH) did not induce the damage effects on A549 cells. ND-paclitaxel was taken into lung cancer cells in a concentration-dependent manner using flow cytometer analysis. The ND-paclitaxel particles were located in the microtubules and cytoplasm of A549 cells observed by confocal microscopy. Furthermore, ND-paclitaxel markedly blocked the tumor growth and formation of lung cancer cells in xenograft SCID mice. Together, we provide a functional covalent conjugation of ND-paclitaxel, which can be delivered into lung carcinoma cells and preserves the anticancer activities on the induction of mitotic blockage, apoptosis and anti-tumorigenesis.

PET imaging using parkinsonian primate model

International Nuclear Information System (INIS)

Nagai, Yuji

2004-01-01

Many animal models have been for studying neutrodegenerative diseases in humans. Among them, Parkinson's disease (PD) model in primates treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is expected to be valid and useful in the field of regenerative medicine. MPTP-treated monkeys demonstrate parkinsonian syndrome, such as tremor, dyskinesia, rigidity, immobility, caused by the degeneration of dopamine neurons at the nigrostriatal pathway. In this model, investigation of cognitive impairment that is one of the important aspects of PD could be possible. We evaluated the degeneration process of nigrostriatal dopamine neurons with positron emission tomography (PET) using unanesthetized MPTP-treated two cynomolgus monkeys (Macaca fascicularis). The tracers used were [11C]PE2I, [11C]DOPA, [11C]raclopride for monitoring dopamine transporter (DAT) densities, dopamine (DA) turnover, dopamine D2-receptor (D2R) densities, respectively. The gross behavioral observation was also performed referring to the criteria of the PD symptoms. The motor dysfunction was not clearly observed up to the cumulative doses of 3 mg/kg MPTP. This period was called 'asymptomatic period'. As a result of PET scans in the asymptomatic period, DAT densities and DA turnover had already decreased greatly, but D2R densities had not changed clearly. These findings suggest that PET imaging can delineate the dopaminergic dysfunction in vivo even in the asymptomatic period. In human study of PD, it is reported that parkinsonism is shown after great loss of dopaminergic neutrons as well as pre-synaptic dysfunction. MPTP-treated monkeys demonstrate the parkinsonian syndrome with the similar mechanism as human PD. It can be expected that PET study with MPTP-monkeys would provide important clues relevant to the underlying cause of PD and be useful for preclinical study of regenerative medicine in this disease. (author)

[Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

Science.gov (United States)

Sasaki, Yuka; Kurashima, Atsuyuki; Morimoto, Kozo; Okumura, Masao; Watanabe, Masato; Yoshiyama, Takashi; Ogata, Hideo; Gotoh, Hajime; Kudoh, Shoji; Suzuki, Hiroaki

2014-11-01

Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

49 CFR 655.11 - Requirement to establish an anti-drug use and alcohol misuse program.

Science.gov (United States)

2010-10-01

... use and alcohol misuse program. Each employer shall establish an anti-drug use and alcohol misuse... 49 Transportation 7 2010-10-01 2010-10-01 false Requirement to establish an anti-drug use and alcohol misuse program. 655.11 Section 655.11 Transportation Other Regulations Relating to Transportation...

Brown-Like Adipocyte Progenitors Derived from Human iPS Cells: A New Tool for Anti-obesity Drug Discovery and Cell-Based Therapy?

Science.gov (United States)

Yao, Xi; Salingova, Barbara; Dani, Christian

2018-04-10

Alternative strategies are urgently required to fight obesity and associated metabolic disorders including diabetes and cardiovascular diseases. Brown and brown-like adipocytes (BAs) store fat, but in contrast to white adipocytes, activated BAs are equipped to dissipate energy stored. Therefore, BAs represent promising cell targets to counteract obesity. However, the scarcity of BAs in adults is a major limitation for a BA-based therapy of obesity, and the notion to increase the BA mass by transplanting BA progenitors (BAPs) in obese patients recently emerged. The next challenge is to identify an abundant and reliable source of BAPs. In this chapter, we describe the capacity of human-induced pluripotent stem cells (hiPSCs) to generate BAPs able to differentiate at a high efficiency with no gene transfer. This cell model represents an unlimited source of human BAPs that in a near future may be a suitable tool for both therapeutic transplantation and for the discovery of novel efficient and safe anti-obesity drugs. The generation of a relevant cell model, such as hiPSC-BAs in 3D adipospheres enriched with macrophages and endothelial cells to better mimic the microenvironment within the adipose tissue, will be the next critical step.

Gastrointestinal Complications Depending on the Selectivity of Non-Steroidal Anti-Inflammatory Drug

Directory of Open Access Journals (Sweden)

G.V. Dzyak

2013-02-01

Full Text Available The article deals with the problem of gastrointestinal complications during administration of nonsteroidal anti-inflammatory drugs, commonly used to treat a range of conditions, particularly rheumatic diseases. The results of own researches, which served to define the characteristics of changes in the state of gastric secretory function in patients receiving non-selective and selective anti-inflammatory agent and their comparative analysis, are provided. The data obtained demonstrated a certain contribution to the understanding of the mechanism of development of complications from the gastrointestinal tract when taken drugs of above group.

Randomised controlled trial examining the effect of exercise in people with rheumatoid arthritis taking anti-TNFα therapy medication.

LENUS (Irish Health Repository)

Reid, Angela

2011-01-01

Substantial progress has been made in the medical management of rheumatoid arthritis (RA) over the past decade with the introduction of biologic therapies, including anti-tumour necrosis factor alpha (anti-TNFα) therapy medications. However, individuals with RA taking anti-TNFα medication continue to experience physical, psychological and functional consequences, which could potentially benefit from rehabilitation. There is evidence that therapeutic exercise should be included as an intervention for people with RA, but to date there is little evidence of the benefits of therapeutic exercise for people with RA on anti-TNFα therapy medication. A protocol for a multicentre randomised controlled three-armed study which aims to examine the effect of dynamic group exercise therapy on land or in water for people with RA taking anti-TNFα therapy medication is described.

A case with Parkinsonism secondary to bilateral subdural hematoma

Directory of Open Access Journals (Sweden)

Adalet Arıkanoğlu

2011-03-01

Full Text Available Subdural hematoma is a rare cause of secondary Parkinsonism. In this study, we presented a case of Parkinsonian syndrome caused by a bilateral subdural hematoma. The patient’s Parkinsonism completely healed following successful surgical removal of the hematomas without any anti-parkinson drug.

The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles.

Science.gov (United States)

Marrelli, Mauro Toledo; Brotto, Marco

2016-11-02

Malaria remains one of the most important infectious diseases in the world, being a significant public health problem associated with poverty and it is one of the main obstacles to the economy of an endemic country. Among the several complications, the effects of malaria seem to target the skeletal muscle system, leading to symptoms, such as muscle aches, muscle contractures, muscle fatigue, muscle pain, and muscle weakness. Malaria cause also parasitic coronary artery occlusion. This article reviews the current knowledge regarding the effect of malaria disease and the anti-malarial drugs on skeletal and cardiac muscles. Research articles and case report publications that addressed aspects that are important for understanding the involvement of malaria parasites and anti-malarial therapies affecting skeletal and cardiac muscles were analysed and their findings summarized. Sequestration of red blood cells, increased levels of serum creatine kinase and reduced muscle content of essential contractile proteins are some of the potential biomarkers of the damage levels of skeletal and cardiac muscles. These biomarkers might be useful for prevention of complications and determining the effectiveness of interventions designed to protect cardiac and skeletal muscles from malaria-induced damage.

Circulating anti-retinal antibodies in response to anti-angiogenic therapy in exudative age-related macular degeneration.

Science.gov (United States)

Kubicka-Trząska, Agnieszka; Wilańska, Joanna; Romanowska-Dixon, Bożena; Sanak, Marek

2014-12-01

To determine changes in anti-retinal antibodies (ARAs) during anti-VEGF therapy in patients with exudative age-related macular degeneration (AMD) and to assess the correlations between ARAs and disease activity. The study comprised 98 patients treated with intravitreal bevacizumab. The ophthalmic examination included best corrected visual acuity (BCVA), slit lamp biomicroscopy, fundoscopy, fluorescein angiography (FA), and optical coherence tomography (OCT). Serum ARAs levels were assessed by indirect immunofluorescence (IIF) on normal monkey retina substrate. These studies were repeated at 4 week intervals within 8 months of a follow-up. The sera of 50 sex- and age-matched healthy subjects were used as controls. At baseline examination, 94 (95.5%) of the 98 patients were positive for ARAs. The ARAs titres were significantly higher (p = 0.0000) than in controls. A positive correlation was found between titres of ARAs and the diameter of choroidal neovascularization (CNV) as measured by FA (p = 0.0000), and central retinal thickness (CRT) assessed by OCT (p = 0.0000). A positive correlation was also found between the diameter of CNV, CRT and the complexity of circulating ARAs. Following treatment all patients demonstrated significant decrease in ARAs levels as well as improvement of BCVA, reduction of subretinal fluid on OCT and decreased leakage on FA. Changes in serum ARAs levels occurred in parallel with clinical outcomes of anti-VEGF therapy. Treatment reduced serum levels of ARAs, with the greatest reduction occurring during the 'loading' phase. This study demonstrated that ARAs may act as a serum biomarker of the efficacy of anti-VEGF therapy. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

WHO HAS THERAPY-RELATED AML?

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Robert Gale

2017-03-01

Full Text Available Therapy-related leukemia or therapy-related myeloid neoplasm are widely-used terms to designate leukemia developing in persons who previously received anti-cancer therapy (for example, see references 1, 2, especially if the prior anti-cancer therapy included drugs such as alkylators, DNA-intercalators, topoisomerase-2-inhibitors, purines and/or ionizing radiations.   Sometimes specific genes such as AML1, EVI1, NRAS or MLL are mutated by therapy or gene variants are produced which activate mutagens or interfere with DNA repair, such FANC, NQ01 or AML2. 3-5   But how can we know if AML in someone is a therapy-related? Keywords: Therapy-related leukemia; alkylators; ionizing radiations; Topoisomerase Inhibitors; DNA Repair

Methadone maintenance therapy as evidence based drug abuse ...

African Journals Online (AJOL)

Methadone maintenance therapy as evidence based drug abuse planning in ... drugs are being used as artificial problem-solvers such as frustrations, stress or ... Drug use is a problem to users when it begins to cause some damage to their ...

Adherence to anti-Parkinson drug therapy in the "REASON" sample of Italian patients with Parkinson's disease: the linguistic validation of the Italian version of the "Morisky Medical Adherence Scale-8 items".

Science.gov (United States)

Fabbrini, G; Abbruzzese, G; Barone, P; Antonini, A; Tinazzi, M; Castegnaro, G; Rizzoli, S; Morisky, D E; Lessi, P; Ceravolo, R

2013-11-01

Information about patients' adherence to therapy represents a primary issue in Parkinson's disease (PD) management. To perform the linguistic validation of the Italian version of the self-rated 8-Item Morisky Medical Adherence Scale (MMAS-8) and to describe in a sample of Italian patients affected by PD the adherence to anti-Parkinson drug therapy and the association between adherence and some socio-demographic and clinical features. MMAS-8 was translated into Italian language by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators and then by two comprehension tests. The translated version of the MMAS-8 scale was then administered at the baseline visit of the "REASON" study (Italian Study on the Therapy Management in Parkinson's disease: Motor, Non-Motor, Adherence and Quality Of Life Factors) in a large sample of PD patients. The final version of the MMAS-8 was easily understood. Mean ± SD MMAS-8 score was 6.1 ± 1.2. There were no differences in adherence to therapy in relationship to disease severity, gender, educational level or decision to change therapy. The Italian version of MMAS-8, the key tool of the REASON study to assess the adherence to therapy, has shown to be understandable to patients with PD. Patients enrolled in the REASON study showed medium therapy adherence.

Estimation of the phase response curve from Parkinsonian tremor.

Science.gov (United States)

Saifee, Tabish A; Edwards, Mark J; Kassavetis, Panagiotis; Gilbertson, Tom

2016-01-01

Phase response curves (PRCs), characterizing the response of an oscillator to weak external perturbation, have been estimated from a broad range of biological oscillators, including single neurons in vivo. PRC estimates, in turn, provide an intuitive insight into how oscillatory systems become entrained and how they can be desynchronized. Here, we explore the application of PRC theory to the case of Parkinsonian tremor. Initial attempts to establish a causal effect of subthreshold transcranial magnetic stimulation applied to primary motor cortex on the filtered tremor phase were unsuccessful. We explored the possible explanations of this and demonstrate that assumptions made when estimating the PRC in a traditional setting, such as a single neuron, are not arbitrary when applied to the case of tremor PRC estimation. We go on to extract the PRC of Parkinsonian tremor using an iterative method that requires varying the definition of the tremor cycle and estimating the PRC at multiple peristimulus time samples. Justification for this method is supported by estimates of PRC from simulated single neuron data. We provide an approach to estimating confidence limits for tremor PRC and discuss the interpretational caveats introduced by tremor harmonics and the intrinsic variability of the tremor's period. Copyright © 2016 the American Physiological Society.

A guided interview process to improve student pharmacists' identification of drug therapy problems.

Science.gov (United States)

Rovers, John; Miller, Michael J; Koenigsfeld, Carrie; Haack, Sally; Hegge, Karly; McCleeary, Erin

2011-02-10

To measure agreement between advanced pharmacy practice experience students using a guided interview process and experienced clinical pharmacists using standard practices to identify drug therapy problems. Student pharmacists enrolled in an advanced pharmacy practice experience (APPE) and clinical pharmacists conducted medication therapy management interviews to identify drug therapy problems in elderly patients recruited from the community. Student pharmacists used a guided interview tool, while clinical pharmacists' interviews were conducted using their usual and customary practices. Student pharmacists also were surveyed to determine their perceptions of the interview tool. Fair to moderate agreement was observed on student and clinical pharmacists' identification of 4 of 7 drug therapy problems. Of those, agreement was significantly higher than chance for 3 drug therapy problems (adverse drug reaction, dosage too high, and needs additional drug therapy) and not significant for 1 (unnecessary drug therapy). Students strongly agreed that the interview tool was useful but agreed less strongly on recommending its use in practice. The guided interview process served as a useful teaching aid to assist student pharmacists to identify drug therapy problems.

Personalized Drug Therapy in Cystic Fibrosis: From Fiction to Reality.

Science.gov (United States)

de Lima Marson, Fernando Augusto; Bertuzzo, Carmen Silvia; Ribeiro, Jose Dirceu

2015-01-01

Personalized drug therapy for cystic fibrosis (CF) is a long-term dream for CF patients, caregivers, physicians and researchers. After years of study, the fiction of personalized treatment has turned to hope. Basic information about CFTR mutations classes and new treatments is needed if we are to deal properly with the new CF era. The problems involved in this issue, however, should be evaluated with greater care and attention. VX-770 is a new drug available to treat CF patients with some class III CFTR mutations and other drugs are being studied regarding other classes. The scientific literature has constantly given information about each therapy, both in vitro and in vivo. The hope is increasing. Nevertheless the "scientific world" still lacks information about patients' reality and daily health related practical needs. Clinical trials have showed good evaluation of some drugs so far, but clinical response is a wide spectrum yet to be analyzed: CFTR mutations spectrum, costs related to the treatment with new drugs (for VX-770 therapy), variability of CF clinical expression, limitations to test in vitro drugs, absence of good clinical markers to evaluate drug response, absence of long-term studies and with patients below six years old, multidrug treatment used to improve the expression response, and finally, the most important problem, who will benefit from the new drugs therapy, are issues that constitute a barrier that should be overcome. Personalized drug therapy may not be a fiction anymore, but it is not yet a reality for all CF patients.

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study.

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Cunningham, Miles G; Yadollahikhales, Golnaz; Vitaliano, Gordana; van Horne, Craig

2016-11-15

Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression. The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. Five years after initiating DBS, during a routine battery change, an apparent electrical event occurred that triggered the rapid onset of severe depression. Anti-seizure and antidepressant medications were ineffective, and the patient was offered a course of electroconvulsive therapy (ECT), which resulted in complete reversal of her depressive episode. Parkinson's syndrome can be seen after a single closed head injury event. Post-traumatic parkinsonism is responsive to DBS; however, DBS has been associated with an infrequent occurrence of dramatic disruption in mood. ECT is a therapeutic option for patients who develop intractable depressive illness associated with DBS.

Interactions of Rosiglitazone and Anti.Arrhythmic Drugs in Animal ...

African Journals Online (AJOL)

Interactions of Rosiglitazone and Anti.Arrhythmic Drugs in Animal Model. YM Mohammed, EI Mohammed, N Mohiuddin, SS Syeda. Abstract. Background: Diabetes increases the risk of vascular problems by two times compared with a healthy individual, with deposition of fats in blood vessel and this includes cardiovascular ...

Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy.

Science.gov (United States)

Anusuya, Shanmugam; Natarajan, Jeyakumar

2012-12-01

Leprosy remains a major public health problem, since single and multi-drug resistance has been reported worldwide over the last two decades. In the present study, we report the novel multi-targeted therapy for leprosy to overcome multi drug resistance and to improve therapeutic efficacy. If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance. The MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were selected for multi targeted therapy. The conserved or class specific active site residues important for function or stability were predicted using evolutionary trace analysis and site directed mutagenesis studies. Ten such residues which were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered based on their position in MurC) were found to be conserved in all the four Mur enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234 and Y329 (numbered based on their position in MurE) were significant in binding substrates and/co-factors needed for the functional events in any three of the Mur enzymes. These are the probable residues for designing newer anti-leprosy drugs in an attempt to reduce drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

NARCIS (Netherlands)

Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

2010-01-01

OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

Nicolau Syndrome after Intramuscular Injection of Non-Steroidal Anti-Inflammatory Drugs (NSAID

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Mehmet Dadaci

2015-01-01

Full Text Available Nicolau syndrome is a rare complication of intramuscular injection that leads to local ischemic necrosis of the skin and adipose tissue. In this paper, we discuss etiologies, risk factors, and treatment options for gluteal Nicolau syndrome referring to patients treated in our hospital. Our study includes 17 women who visited our clinic with symptoms of gluteal necrosis secondary to intramuscular injection. The following variables were taken into account: injection site, drug administered, frequency of injections, the person who administered the injections, needle size, and needle tip color. Magnetic resonance images obtained in the aftermath of intramuscular injection application were carefully analyzed for presence of necrosis, cyst formation and the thickness of the gluteal fat tissue layer. Drugs that had been received in intramuscular injection were exclusively non-steroidal anti-inflammatory drugs. Mean patient BMI was 41.8 (all patients were considered as obese, and mean gluteal fat thickness was 54 mm. Standard length of needles (3.8 cm had been used in procedures. The wounds were treated with primary closure in 11 patients and with local flap therapy in 6 patients. The observed necrosis was a consequence of misplaced gluteal injection, where drugs were injected into the adipose tissue instead of the muscle due to the extreme thickness of the fat layer, on one hand, and the inappropriate length of standard needles, on the other hand. Intramuscular injection should be avoided in obese patients whenever possible: if it is necessary, proper injection technique should be used.

Tamsulosin Monotherapy versus Combination Therapy with Antibiotics or Anti-Inflammatory Agents in the Treatment of Chronic Pelvic Pain Syndrome

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Tae Hyo Kim

2011-06-01

Full Text Available Purpose Chronic pelvic pain syndrome (CPPS is treated by use of various protocols. We compared tamsulosin monotherapy with tamsulosin in combination with antibiotics or anti-inflammatory agents and evaluated the efficacy of these treatments in patients with CPPS. Methods Patients (n=107 who were younger than 55 years and diagnosed with CPPS were randomly assigned to treatment with tamsulosin at 0.2 mg (group A, tamsulosin at 0.2 mg plus anti-inflammatory drugs (group B or tamsulosin at 0.2 mg plus antibiotics (group C daily. We applied the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI and the International Prostate Symptom Score (IPSS to evaluate 100 patients who were treated for 12 weeks (7 withdrew. Scores of the three groups were compared by analysis of variance and we also evaluated subscores, which included pain, voiding and quality of life (QoL. Results All three groups showed statistically significant decreases in NIH-CPSI score, IPSS and subscore scores (P<0.05. There were no statistically significant differences between the groups except for the QoL domain of the IPSS (group A vs. C; P<0.01. Conclusions Tamsulosin monotherapy for 12 weeks was effective for treating patients with CPPS, compared with combination therapy with antibiotics or anti-inflammatory drugs.

Treating angina pectoris by acupuncture therapy.

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Xu, Lixian; Xu, Hao; Gao, Wei; Wang, Wei; Zhang, Hui; Lu, Dominic P

2013-01-01

Acupuncture therapy on PC 6 (Neiguan) has a therapeutic effect on cardiac and chest ailments including angina pectoris. Additional beneficial acupuncture points are PC 4 (Ximen), HT 7 (Shenmen point), PC 7 (Daling point), PC 5 (Jianshi point), PC 3 (Quze point), CV 17 (Danzhong point), CV 6 (Qihai point), BL 15 (Xinshu point), L 20 (Pishu point), BL 17 (Geshu point), BL23 (Shenshu point), BL18 (Ganshu point), HT 5 (Tongli point), and ST36 (Zusanli point). Acupuncture not only quickly relieve the symptoms of acute angina pectoris, but also improve nitroglycerine's therapeutic effects. Therefore, it is an efficient simple therapeutic method used for emergency and for regular angina treatment. Review of studies on acupuncture therapy has shown effectiveness were between 80% to 96.2% that are almost as effective as conventional drug regimen. When compared with conventional medical treatment, the acupuncture therapy shows the obvious advantage of lacking, adverse side effects commonly associated with the Western anti-anginal drugs such as 1) Nitroglycerine (headache--63% with nitroglycerine patch and 50% with spray; syncope--4%; and dizziness--8% with patch; hypotension--4% with patch; and increased angina 2% with patch). 2) Isosorbide mononitrate (dizziness--3 to 5%; nausea/vomiting--2 to 4% and other reactions including hypotension, and syncope even with small doses). 3) Propranolol (bradycardia, chest pain, hypotension, worsening of AV conduction disturbance, Raynaud's syndrome, mental depression, hyperglycemia, etc.). Many conventional anti-anginal medications cause inter-drug reactions with other medications the patients taking for other diseases. Whereas, acupuncture therapy does not pose such an interference with patient's medications. Nevertheless, surgery is still the treatment of choice when acupuncture or conventional drug therapy fails. Combination of conventional drug therapy and acupuncture would considerably decrease the frequency and the required dosage

PhytoNanotechnology: Enhancing Delivery of Plant Based Anti-cancer Drugs

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Tabassum Khan

2018-02-01

Full Text Available Natural resources continue to be an invaluable source of new, novel chemical entities of therapeutic utility due to the vast structural diversity observed in them. The quest for new and better drugs has witnessed an upsurge in exploring and harnessing nature especially for discovery of antimicrobial, antidiabetic, and anticancer agents. Nature has historically provide us with potent anticancer agents which include vinca alkaloids [vincristine (VCR, vinblastine, vindesine, vinorelbine], taxanes [paclitaxel (PTX, docetaxel], podophyllotoxin and its derivatives [etoposide (ETP, teniposide], camptothecin (CPT and its derivatives (topotecan, irinotecan, anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin, and others. In fact, half of all the anti-cancer drugs approved internationally are either natural products or their derivatives and were developed on the basis of knowledge gained from small molecules or macromolecules that exist in nature. Three new anti-cancer drugs introduced in 2007, viz. trabectedin, epothilone derivative ixabepilone, and temsirolimus were obtained from microbial sources. Selective drug targeting is the need of the current therapeutic regimens for increased activity on cancer cells and reduced toxicity to normal cells. Nanotechnology driven modified drugs and drug delivery systems are being developed and introduced in the market for better cancer treatment and management with good results. The use of nanoparticulate drug carriers can resolve many challenges in drug delivery to the cancer cells that includes: improving drug solubility and stability, extending drug half-lives in the blood, reducing adverse effects in non-target organs, and concentrating drugs at the disease site. This review discusses the scientific ventures and explorations involving application of nanotechnology to some selected plant derived molecules. It presents a comprehensive review of formulation strategies of phytoconstituents in

Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

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Way-Seah Lee

2017-10-01

Full Text Available Anti-tumor necrosis factor (anti-TNF is highly effective in inflammatory bowel disease (IBD; however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years. All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia. All 3 patients died within 1 year from the onset of the infection(s. We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

18F FDG PET/CT in differential diagnosis of Parkinsonian disorders

International Nuclear Information System (INIS)

Deepa; Moon, S.; Mahajan, S.; Thapa, P.; Gupta, P.; Sahana; Tripathi, M.; Sharma, R.; Mondal, A.; Batla, A.; Nehru, R.; Kushwaha, S.; Mishra, A.K.

2010-01-01

Full text: Differential diagnosis of Parkinsonian disorders can be challenging in the early phase of disease course. Positron Emission Tomography (PET) imaging with 18 F Fluorodeoxyglucose (FDG) has been used to identify characteristic patterns of glucose metabolism in patients with idiopathic Parkinson's Disease (PD) as well as variant forms of Parkinsonism such as Multisystem Atrophy (MSA), Progressive Supranuclear Palsy (PSP) and cortico basal ganglionic degeneration (CBGD). In this study we assessed the utility of 18 F FDG PET/CT in the differential diagnosis Parkinsonian syndromes. 66 Parkinsonian patients with a mean age of 59.6 ± 11.50 years, male: female ratio of 3.12:1, age range of 35-84 years with a disease duration of 2.6 ± .68 years were referred for FDG PET to determine whether their scan patterns could distinguish idiopathic Parkinsons from the Parkinson plus syndromes. Approximately 60 minutes following intravenous injection of 370 MBq of 18 F-FDG, PET/CT scan of the brain was acquired in a whole-body Full Ring PET/CT scanner (Discovery STE16 camera). A low dose CT was obtained on the same area without IV contrast for attenuation correction and coregistration. Images were reconstructed using a 3D VUE algorithm and slices were reformatted into transaxial, coronal and sagittal views. Subsequently the images were processed and visually analyzed on Xeleris workstation. Images were classified by visual analysis into the various subgroups, those with normal to increased basal ganglia uptake were classified into Idiopathic Parkinson's (40/45) and when basal ganglia uptake was decreased they were Parkinsons Plus (19/21). The study demonstrates that 18 F FDG PET performed at the time of initial referral for parkinsonism could accurately classify patients into Parkinson's disease and Parkinson plus subtypes

A strategy to find novel candidate anti-Alzheimer's disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants.

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Chen, Bi-Wen; Li, Wen-Xing; Wang, Guang-Hui; Li, Gong-Hua; Liu, Jia-Qian; Zheng, Jun-Juan; Wang, Qian; Li, Hui-Juan; Dai, Shao-Xing; Huang, Jing-Fei

2018-01-01

Alzheimer' disease (AD) is an ultimately fatal degenerative brain disorder that has an increasingly large burden on health and social care systems. There are only five drugs for AD on the market, and no new effective medicines have been discovered for many years. Chinese medicinal plants have been used to treat diseases for thousands of years, and screening herbal remedies is a way to develop new drugs. We used molecular docking to screen 30,438 compounds from Traditional Chinese Medicine (TCM) against a comprehensive list of AD target proteins. TCM compounds in the top 0.5% of binding affinity scores for each target protein were selected as our research objects. Structural similarities between existing drugs from DrugBank database and selected TCM compounds as well as the druggability of our candidate compounds were studied. Finally, we searched the CNKI database to obtain studies on anti-AD Chinese plants from 2007 to 2017, and only clinical studies were included. A total of 1,476 compounds (top 0.5%) were selected as drug candidates. Most of these compounds are abundantly found in plants used for treating AD in China, especially the plants from two genera Panax and Morus. We classified the compounds by single target and multiple targets and analyzed the interactions between target proteins and compounds. Analysis of structural similarity revealed that 17 candidate anti-AD compounds were structurally identical to 14 existing approved drugs. Most of them have been reported to have a positive effect in AD. After filtering for compound druggability, we identified 11 anti-AD compounds with favorable properties, seven of which are found in anti-AD Chinese plants. Of 11 anti-AD compounds, four compounds 5,862, 5,863, 5,868, 5,869 have anti-inflammatory activity. The compound 28,814 mainly has immunoregulatory activity. The other six compounds have not yet been reported for any biology activity at present. Natural compounds from TCM provide a broad prospect for the

Orexin Receptor Targets for Anti-Relapse Medication Development in Drug Addiction

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Ronald E. See

2011-06-01

Full Text Available Drug addiction is a chronic illness characterized by high rates of relapse. Relapse to drug use can be triggered by re-exposure to drug-associated cues, stressful events, or the drug itself after a period of abstinence. Pharmacological intervention to reduce the impact of relapse-instigating factors offers a promising target for addiction treatment. Growing evidence has implicated an important role of the orexin/hypocretin system in drug reward and drug-seeking, including animal models of relapse. Here, we review the evidence for the role of orexins in modulating reward and drug-seeking in animal models of addiction and the potential for orexin receptors as specific targets for anti-relapse medication approaches.

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

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Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

2016-01-01

Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

Factors associated with anti-tuberculosis medication adverse effects: a case-control study in Lima, Peru.

Science.gov (United States)

Chung-Delgado, Kocfa; Revilla-Montag, Alejandro; Guillen-Bravo, Sonia; Velez-Segovia, Eduardo; Soria-Montoya, Andrea; Nuñez-Garbin, Alexandra; Silva-Caso, Wilmer; Bernabe-Ortiz, Antonio

2011-01-01

Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use. A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005-2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65-9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17-3.89), anemia (OR = 2.10; IC95%: 1.13-3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29-19.6), and smoking (OR = 2.00; 95%CI: 1.03-3.87) were independently associated with adverse drug reactions. Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.

Factors associated with anti-tuberculosis medication adverse effects: a case-control study in Lima, Peru.

Directory of Open Access Journals (Sweden)

Kocfa Chung-Delgado

Full Text Available BACKGROUND: Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use. METHODOLOGY AND RESULTS: A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005-2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR and 95% confidence intervals (95%CI. A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65-9.35, overweight/obesity (OR = 2.13; 95%CI: 1.17-3.89, anemia (OR = 2.10; IC95%: 1.13-3.92, MDR-TB medication (OR = 11.1; 95%CI: 6.29-19.6, and smoking (OR = 2.00; 95%CI: 1.03-3.87 were independently associated with adverse drug reactions. CONCLUSIONS: Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.

Use of non-steroidal anti-inflammatory drugs and nutritional ...

African Journals Online (AJOL)

Background. The use of medications by football players in many populations is known to be high. Data on African players are scarce. Objective. To determine the magnitude of use of non-steroidal anti-inflammatory drugs (NSAIDs) and nutritional supplements by Zimbabwean football players. Methods. We conducted a ...

Lipid nano-bubble combined with ultrasound for anti-keloids therapy.

Science.gov (United States)

Wang, Xiao Qing; Li, Zhou-Na; Wang, Qi-Ming; Jin, Hong-Yan; Gao, Zhonggao; Jin, Zhe-Hu

2018-03-01

Keloids were characterized by excessive growth of fibrous tissues, and shared several pathological characteristics with cancer. They did put physical and emotional stress on patients in that keloids could badly change appearance of patients. N-(4-hydroxyphenyl) retinamide (4HPR) showed cytotoxic activity on a wide variety of invasive-growth cells. Our work was aim to prepare N-(4-hydroxyphenyl) retinamide-loaded lipid microbubbles (4HPR-LM) combined with ultrasound for anti-keloid therapy. 4HPR-loaded liposomes (4HPR-L) were first prepared by film evaporation method, and then 4HPR-LM were manufactured by mixing 4HPR-L and perfluoropentane (PFP) with ultrasonic cavitation method. The mean particle size and entrapment efficiency 4HPR-LM were 113 nm and 95%, respectively. The anti-keloids activity of 4HPR-LM was assessed with BALB/c nude mice bearing subcutaneous xenograft keloids model. 4HPR-LM, combined with ultrasound, could significantly induce apoptosis of keloid fibroblasts in vitro and inhibited growth of keloids in vivo. Thus, 4HPR-LM could be considered as a promising agent for anti-keloids therapy.

Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study testing antibodies, RNA and Genotype of HCV in Baghdad.

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Al-Kubaisy, Waqar; Daud, Suzanna; Al-Kubaisi, Mustafa Waseem; Al-Kubaisi, Omar Waseem; Abdullah, Nik Nairan

2018-04-30

Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV