The main goal of local drug delivery is to increase the concentration of a specific therapeutic agent in a target tissue with minimal nontarget distribution. Compared to systemic therapy, local drug delivery provides a high level of therapeutic efficacy with minimal systemic effects. The current primary imaging modality for drug delivery has been x-ray angiography, but it has major limitations including anatomical ambiguity and inability to visualize the targeted tissues. Due to these inherent problems, MR guidance has been explored as an alternative imaging modality for guiding and monitoring of drugtherapy. Recently, interventional MR (XMR) systems have been implemented that have both dual x-ray and MRI capabilities in a single suite and allow for real-time interventional procedures to ...
The long and resource intensive process of drug discovery and development is confronted with the basic challenge of providing effective and safe therapies at reasonably low costs. The better the mechanism of a disease is known, the higher the probability to find an appropriate therapy. Also, the better and earlier a disease can be diagnosed and characterized, the higher the chance to be able to interfere in this process with a chemical entity. This reasoning sets the framework for the use of imaging in drug discovery. We discuss the relevance of magnetic resonance imaging and spectroscopy to derive anatomical, functional, metabolic and target-related information in the context of pharmacological research in vivo. (author)
BackgroundStem cell characteristics are an important feature of human cancer cells and play a major role in the therapy resistance of tumours. Strategies to target cancer stem cells...Full Text Available
Upconversion nanoparticles (UCNPs) with unique multi-photon excitation photoluminescence properties have recently been intensively explored as novel contrast agents for low-backgroundbiomedical imaging. In this work, we functionalize UCNPs with a polyethylene glycol (PEG) grafted amphiphilic polymer. The PEGylated UCNPs are loaded with a commonly used chemotherapy molecule, doxorubicin (DOX), by simple physical adsorption via a supramolecular chemistry approach for intracellular drug delivery. The loading and releasing of DOX from UCNPs are controlled by varying pH, with an increased drug dissociation rate in acidic environment, favorable for controlled drug release. Upconversion luminescence (UCL) imaging by a modified laser scanning confocal microscope reveals the time course of intracel...
Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which ha...
Anxiety disorders are a highly prevalent and disabling class of psychiatric disorders. This review focuses on new directions in neurobiological research and implications for the development of novel psychopharmacological treatments. Neuroanatomical and neuroimaging research in anxiety disorders has centered on the role of the amygdala, reciprocal connections between the amygdala and the prefrontal cortex, and, most recently, alterations in interoceptive processing by the anterior insula. Anxiety disorders are characterized by alterations in a diverse range of neurochemical systems, suggesting ample novel targets for drugtherapies. Corticotropin-releasing factor (CRF) concentrations are elevated in a subset of anxiety disorders, which suggests the potential utility of CRF receptor antagoni...
This joint statement was developed by the CMA and the Canadian Pharmaceutical Association, a national association of pharmacists, and includes the goal of drugtherapy, strategies for collaboration...Full Text Available
HIV-1 nonsubtype B variants account for the majority of HIV infections worldwide. Drug resistance in individuals who have never undergone antiretroviral therapy can lead to early failure and...Full Text Available
SummaryEpigenetic drugs have been shown to enhance gene expression and drug sensitivity in ovarian cancer cell lines and animal models. Based on promising pre-clinical studies,...Full Text Available
PurposeTo identify the extent of persistence (period of time of continuous therapy with the drug prescribed) of glaucoma patients treated with prostaglandins (latanoprost, bimatoprost,...Full Text Available
Invasive fungal infections can be devastating, particularly in immunocompromised patients, and difficult to treat with systemic drugs. Furthermore, systemic administration of those medications...Full Text Available
The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapytarget. Significant advancements have been made in understanding...Full Text Available
BackgroundArtemisinin-based combination therapy, currently considered the therapy of choice for uncomplicated Plasmodium falciparum malaria in endemic countries,...Full Text Available
Somatic cell nuclear transfer or therapeutic cloning has provided great hope for stem cell-based therapies. However therapeutic cloning has been experiencing both ethical and technical difficulties....Full Text Available
ObjectiveTo evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in...Full Text Available
Control of human filarial infections currently depends on chemotherapeutic strategies predominantly directed at microfilariae. Doxycycline therapy in an extended daily dose regimen sterilizes and kills adult stages, but the utility of this drug for routine field use remains an issue of concern. No macrofilaricidal drugs with efficacy after one or two doses are available for use, delaying the achievement of the elimination or eradication of onchocerciasis and lymphatic filariasis. Moxidectin, a macrocyclic lactone, is currently in clinical trials for onchocerciasis. A few other drugs that have already been approved for use in veterinary practice or in human medicine for other indications are available for investigation. Early drug discovery pipelines are poorly populated and the process of ...
Two patients are described in whom sunburn and electron beam radiodermatitis, respectively, were critical determinants in localizing the initial presentation of drug eruptions. In the first instance, a severe sunburn of the back and thighs was followed 7 months later by the appearance of a toxic epidermal necrolysis drug reaction to trimethoprim-sulfamethoxazole in the exact sites of the previous bullous sunburn reaction. In the second patient, a radiodermatitis of the left upper arm due to electron beam therapy for metastatic breast cancer was followed 7 weeks later by a codeine drug reaction confined to the area of the radiodermatitis. In both instances, oral rechallenge with the offending drug reproduced the eruption.
Background: Determinants of warfarin use and anticoagulation levels in atrial fibrillation (AF) patients have not been clarified thoroughly. Methods and Results: A total of 6,324 patients with non-valvular AF and congestive heart failure, hypertension, age, diabetes, prior stroke (CHADS(2)) score ?1 were used to investigate determinants of warfarin use, and 6,932 patients with AF receiving warfarin were used to investigate determinants of international normalized ratio (INR) of prothrombin time. Target INR levels for non-valvular AF patients were 1.6-2.6 for patients aged ?70 years and 2-3 for patients aged transient ischemic attack (TIA), and had higher CHADS(2) scores than those not receiving warfarin. Determinants of warfarin use were age (?60 years), AF type (persistent and permanent), and comorbidities (congestive heart failure, diabetes mellitus, and prior stroke or TIA). Use of antiplatelet drugs was a negative determinant of warfarin ...
Magnetic drugtargeting, using core-shell magnetic carrier particles loaded with anti-cancer drugs, is an emerging and significant method of cancer treatment. Gold shell-iron core nanoparticles (Fe@Au) were synthesized by the reverse micelle method with aqueous reactants, surfactant, co-surfactant and oil phase. XRD, XPS, TEM and magnetic property measurements were utilized to characterize these core-shell nanoparticles. Magnetic measurements showed that the particles were superparamagnetic at room temperature and that the saturation magnetization decreased with increasing gold concentration. The anti-cancer drug doxorubicin (DOX) was loaded onto these Fe@Au nanoparticle carriers and the drug release profiles showed that upto 25% of adsorbed drug was released in 80 h. It was found that the amine (-NH2) group of DOX binds to the gold shell. An in vitro apparatus ...
Human antibodies targeting prostate cancer cell surface epitopes may be useful for imaging and therapy. The objective of this study was to evaluate the tumor targeting of an internalizing human...Full Text Available
To capitalize on the response of tumor cells to ionizing radiation, we developed a controlled-release nanoparticle drug delivery system using a targeting peptide that recognizes a radiation-induced...Full Text Available
The phenomenon of antibiotic resistance has created a need for the development of novel antibiotic classes with non-classical cellular targets. Unfortunately, target-based drug discovery against...Full Text Available
An electron accelerator unit is described for electron beam therapy, comprising: a source of an electron beam; means for finally directing at least a portion of the beam to a therapy site, the directing means being mechanically independent of, and electrically isolated from, the source, and having a target area; and means for aligning the source with the directing means, the aligning means comprising means for projecting at least one beam of light from the source toward the target area.
An electron accelerator unit is described for electron beam therapy, comprising: a source of an electron beam; means for finally directing at least a portion of the beam to a therapy site, the directing means being mechanically independent of, and electrically isolated from, the source, and having a target area; and means for aligning the source with the directing means, the aligning means comprising means for projecting at least one beam of light from the source toward the target area.
Current antidotal regimens for organophosphorus compound (OP) poisoning consist of a combination of pretreatment with a spontaneously reactivating AChE inhibitor such as pyridostigmine bromide, and postexposure therapy with anticholinergic drugs such as atropine sulfate and oximes such as 2-PAM chloride (Gray, 1984). Although these antidotal regimens are effective in preventing lethality of animals from OP poisoning, they do not prevent postexposure incapacitation, convulsions, performance deficits, or, in many cases, permanent brain damage (Dunn and Sidell, 1989). These problems stimulated the development of enzyme bioscavengers as a pretreatment to sequester highly toxic OPs before they reach their physiological targets. Several studies over the last two decades have demonstrated that exogenously administered human serum butyrylcholinesterase (Hu BChE) can be used successfully as a safe, efficacious, and single ...
BackgroundDespite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.MethodsWe focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.ResultsIt was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, ...
Chronic pain patients who show aberrant drug-related behavior often are discontinued from treatment when they are noncompliant with their use of opioids for pain. The purpose of this study was...Full Text Available
BackgroundThe precise mechanisms involved in the initiation and progression of rheumatoid arthritis (RA) are not known. Early stages of RA often have non-specific symptoms, delaying...Full Text Available
The development of azole resistance in Candida albicans is most problematic in patients with AIDS who receive long courses of drug for therapy or prevention of oral candidiasis. Recently,...Full Text Available
Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available
The heterogeneity of metastatic breast cancer mandates the need to select therapies taking into account tumor and patient characteristics. Chemotherapy is indicated in the palliative setting especially...Full Text Available
Magnetic particles have become very promising materials for drug delivery. However, preparation of magnetite particles with high surface area, biocompatibility, strong magnetic response, and suitable particle size still remains a major challenge. In this report, magnetite nanocrystal clusters with high surface areas were fabricated through a solvothermal process by introducing ammonium acetate as a porogen and trisodium citrate as a surface modification agent. The porosity, which was controlled by the reactant concentration, has been investigated in detail. The surface area of the nanocrystal clusters was as high as 141?m(2) g(-1) . Ibuprofen, as a model drug, was entrapped into the magnetite carriers. The interfacial interaction between the carboxylic groups on the drug molecules and the carboxylate groups on the carriers enhanced the loading efficiency. Low cytotoxicity in MCF-7 cell and in vitro constant ...
The success of monoclonal antibodies in clinical practice is dependent on good design. Finding a suitable target is the most important part as other properties of the antibody can be altered by genetic...Full Text Available
The potential of radiolabelled phenylpiperazines as agents for the detection and therapy of tumours of neural crest origin was evaluated by in vitro pharmacological studies with human neuroblastoma...Full Text Available
A previously healthy young man experienced several episodes of syncope while being treated with tenofovir, emtricitabine and nevirapine initiated during primary HIV-1 infection. Symptoms disappeared after discontinuation of antiretroviral therapy and we suggest that syncope may be a side effect to one of the three antiretroviral drugs that has not been described previously.
PurposeWe conducted a comparative study of Clinical Target Volume (CTV) definition of pelvic lymph nodes by multiple GU radiation oncologists looking at the levels...Full Text Available
Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the ...
Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. In addition, the preferred method of tumor resection has changed; limb salvage has nearly replaced amputation of the affected limb. Limb salvage procedures can be performed in place of amputation without compromising patient survival rates. Recent studies have revealed that the pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, which is most commonly the Fli1 gene on chromosome 11, are implicated in more than 95% of ...
Electron beam therapy has often been used for radiation therapy of carcinomas of the buccal mucosa, though side effects, including stomatitis and dermatitis, are known to exist. We experimented using the additional back scatter and transit with the phantom under a lead plate within the irradiation field, in order to better focus the dose on the target volume moreover, we fabricated a mouthpiece fitted with a lead plate shaped to the target volume, and with respect to the influence of the mouthpiece on stomatitis and dermatitis, obtained good clinical results. (author).
Electron beam therapy has often been used for radiation therapy of carcinomas of the buccal mucosa, though side effects, including stomatitis and dermatitis, are known to exist. We experimented using the additional back scatter and transit with the phantom under a lead plate within the irradiation field, in order to better focus the dose on the target volume moreover, we fabricated a mouthpiece fitted with a lead plate shaped to the target volume, and with respect to the influence of the mouthpiece on stomatitis and dermatitis, obtained good clinical results. (author).
Conformal radiation therapy represents a considerable and attractive challenge in oncology. Its aim is mainly to improve local control by increasing the dose with an acceptable rate of complications. This work overviews the world literature on this subject. The technical and theoretical requirements are highlighted. These requirements include a precise definition of the target volume by digital imaging (essentially CT scan), but also clear view of the target volume and the organs at risk, a specific collimation of the beam, 3-D dose calculations, optimization procedures, and a rigid immobilization of the patient with verification of his position. Moreover, the clinical applications of conformal radiation therapy are reviewed and discussed. (authors). 80 refs., 1 tab.
A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants [such as peroxynitrite (OONO−)]...Full Text Available
Convection-enhanced delivery (CED) has emerged as a promising method of targeteddrug-delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate...Full Text Available
BackgroundGene expression profiling and the analysis of protein-protein interaction (PPI) networks may support the identification of disease bio-markers and potential drugtargets....Full Text Available
The antitumor agent camptothecin targets DNA topoisomerase I by reversibly stabilizing a covalent enzyme-DNA intermediate. The subsequent collision of DNA replication forks with these drug-enzyme-DNA...Full Text Available
Essential in mitosis, the human Kinesin-5 protein is a target for >80 classes of allosteric compounds that bind to a surface-exposed site formed by the L5 loop. Not established is why there...Full Text Available
Drug particle size distribution has a profound impact to the content uniformity in low-dose solid drug products. We derived theoretically the skewness of potency distribution as a function of particle size distribution and target dose. It was demonstrated that both skewness and coefficient of variation diverge simultaneously with inverse square root of the target dose. This scaling relation was observed in recent experiment and was verified by Monte Carlo (MC) simulation, which was employed for the first time to solve for the full potency distribution from a random retrieving model. When tested against the criteria from USP uniformity of dosage units, MC simulation showed a striking anisotropic distribution of the data. This suggests a full-scale consideration of the potency distribu...
A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspension was evaluated on Indian earthworms (Pheretima poi). Metronidazole magnetic nanosuspension at a dose of 10 and 50 mg/ml shortened by 31% and 34%, respectively, the mean time to death of the earthworms when compared against a non-magnetic metronidazole suspension. Thus, the developed metronidazole magnetic nanosuspension showed potent, controlled and targeteddrug action and might be a good therapeutic avenue in combating infectious GI disorders.
Despite high local control rate in Ewing's sarcoma the exact indication of radiation therapy is still controversial as well as the choice of the target volume and the optimal dose of radiation. The importance of the quality of radiotherapy has been stressed in recently published data and has shown a significant impact on long term local control with adequate radiation therapy. The dramatic improvement of precision allowed by the conformal therapy and three dimensional dosimetry allow to expect a decrease of late effects expected for second malignancies. However, late sequelae and radio-induced osteosarcoma still remain the major side effects after radiotherapy. The authors discuss the results of the main trials on Ewing's sarcoma on the choice of dose and target volume. Surgery is still the preferred choice for small tumors if the foreseen outcome is identical. (authors). 28 refs.
AbstractThe optimal definition of the size, shape and location of gross tumour volume is one of the most important steps in the planning of radiation therapy, and necessitates a proper...Full Text Available
Monogenic autoinflammatory diseases encompass a distinct and growing clinical entity of multisystem inflammatory diseases with known genetic defects in the innate immune system. The diseases...Full Text Available
The 37/67-kd laminin receptor, LAMR, is a multifunctional protein that associates with the 40S ribosomal subunit and also localizes to the cell membrane to interact with the extracellular matrix. LAMR...Full Text Available
BackgroundIntrafractional motion results in local over- and under-dosage in particle therapy with a scanned beam. Scanned beam delivery offers the possibility to compensate target...Full Text Available
Neuropilin-1 (NRP1) acts as a co-receptor for class 3 semaphorins and vascular endothelial growth factor and is an attractive angiogenesis target for cancer therapy. In addition to the transmembrane...Full Text Available
An increased compendium of drugs useful in ocular motor system dysfunction has expanded our capacity to treat selected ocular motility disorders. Adjunctive therapeutic modes (e.g., Fresnel prisms and orthoptic exercises) can also be beneficial. PAN and see-saw nystagmus can be treated with baclofen. Downbeat nystagmus may respond to clonazepam therapy, and prisms may help if the nystagmus can be modified with convergence. Congenital nystagmus may respond minimally to drugs (e.g., baclofen), but prisms or surgical procedures, or both, are still the primary treatment modalities. Innovar may be helpful in patients with severe, incapacitating vestibular disorders, and scopolamine alone or in combination with promethazine may be beneficial in patients with milder ambulatory acute peripheral vestibular disorders. Benign positional vertigo is best treated initially with positional exercises before drug ...
The role of radiation therapy in local tumor control and decreased incidence of pulmonary metastasis is reported in 271 patients who were entered into the Intergroup Ewing's Sarcoma Study with more than one year follow-up and on whom all radiotherapy records were reviewed. The majority of the patients were irradiated to the primary tumor with doses of 4500 to 6500 rad in five to six weeks in combination with systemic administration of three drugs (vincristine, actinomycin-D and cyclophosphamide) or four drugs (vincristine, actinomycin-D, cyclophosphamide and adriamycin). One of the groups of patients was treated with three drugs and bilateral pulmonary irradiation (1500 rad, uncorrected dose, in two weeks). Preliminary analysis shows an overall local primary tumor control of 89%. Patients with lesions in the pelvis had a local failure rate of 17% (9 of 52) and in the humerus 23% (7 of 31). Factors ...
A novel drug delivery system for the treatment of brain tumors was formulated by methotrexate (MTX)-loaded polymeric nanoparticles (NPs) based on Glycol chitosan (GCS) and Dextran sulfate (DS). The physicochemical properties of resulting particles were investigated, evidencing the contribution of these nanoparticles for brain targeting. In vitro release of MTX was also evaluated. The GCS-DS nanoparticles have been developed based on the modulation of ratio show promise as a system for controlled delivery of the drug to the brain. PMID:21782844
Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic ...
Abstract Imatinib mesylate is the first of a novel group of drugs that specifically target protein tyrosine kinases, which are central to the pathogenesis of human cancer. It has been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor and has been found efficacious in other neoplastic diseases. Nilotinib and dasatinib, a second-generation of tyrosine kinase inhibitors (TKIs), were developed in response to findings of emerging imatinib resistance or intolerance to the drug. Cutaneous reactions are the most common nonhematologic side effect of these drugs, and their management is challenging especially in the absence of alternative anticancer agents. The present review focuses on the clinical characteristics and the hypothesized molecular pathogenesis o...
The world of antibiotic drug discovery and development is driven by the necessity to overcome antibiotic resistance in common Gram-positive and Gram-negative pathogens. However, the lack of Gram-negative activity among both recently approved antibiotics and compounds in the developmental pipeline is a general trend despite the fact that the plethora of covered drugtargets are well-conserved across the bacterial kingdom. Such intrinsic resistance in Gram-negative bacteria is largely attributed to the activity of multidrug resistance (MDR) efflux pumps. Moreover, these pumps also play a significant role in acquired clinical resistance. Together, these considerations make efflux pumps attractive targets for inhibition in that the resultant efflux pump inhibitor (EPI)/antibiotic combination d...
Isolation of functional and intact mitochondria from solid tissue is crucial for studies that focus on the elucidation of normal mitochondrial physiology and/or mitochondrial dysfunction in conditions such as aging, diabetes, and cancer. There is growing recognition of the importance of mitochondria both as targets for drug development and as off-target mediators of drug side effects. Unfortunately, mitochondrial isolation from tissue is generally carried out using homogenizer-based methods that require extensive operator experience to obtain reproducible high-quality preparations. These methods limit dissemination, impede scale-up, and contribute to difficulties in reproducing experimental results over time and across laboratories. Here we describe semiautomated methods to disrupt tissue ...
This paper is a progress report on the role of radiation therapy (RT) in local tumor control and the decreased incidence of pulmonary metastasis in 251 patients entered in the Intergroup Ewing's Sarcoma Study. All were followed for more that 1 year, and their RT records were reviewed. Doses to the primary tumor in the range of 4,500--6,500 rad were administered over approximately 5 to 6 weeks in combination with 4 drugs, i.e., vincristine (VCR), dactinomycin (DAC), cyclophosphamide (CY), and adriamycin, or only the first 3. One group of patients received the 3 drugs and bilateral pulmonary irradiation (approximately 1,500 rad in 2 wk). Preliminary analysis showed a local primary tumor control of approximately 90%. Patients with lesions in the pelvis and humerus had local failure rates of 13% (7 of 54) and 21.4% (6 of 28), respectively. The treatment groups differed significantly in the incidence of pulmonary metastasis. ...
PP2B is a Ca2+/calmodulin-dependent protein phosphatase that is ubiquitously expressed in mammals. Among other actions, it is an effector mechanism in NMDA-mediated glutamate neurotransmission as well as a regulator of GSK3? and MAPK signaling cascades. Because all of these mechanisms have demonstrable roles in the control of circadian rhythyms, we hypothesized that PP2B would be a key regulator of rhythm generation and entrainment, and that through inhibition of its phosphatase activity, the circadian system would be affected by immunosuppressant drugtherapy. We report here that immunosuppressant drugs (cyclosporin A, FK506) (1) block the circadian responses to light that underlie photic entrainment; (2) produce circadian phase shifts with a characteristic nonphotic profile; and (3) disr...
Background: the authors report on the conception and first clinical application of a donut-shaped high-dose configuration for proton therapy (PT). This approach allows one to intensify target volume dose coverage for targets encompassing a critical, dose-limiting structure - like here, the cauda equina -, whilst delivering minimal dose to other healthy structures surrounding the target, thereby reducing the integral dose. Methods and results: intensity-modulated PT methods (IMPT) for spot scanning were applied to create and deliver a donut-shaped high-dose configuration with protons, allowing treating > 75% of the target with at least 95% of the prescribed dose of 72.8 CGE, whilst restricting dose to the cauda equina to 60-65 CGE. Integral dose was lower by a factor of 3.3 as compared to intensity-modulated radiotherapy with photons (IMXT). Conclusion: IMPT and spot scanning ...
Background: the authors report on the conception and first clinical application of a donut-shaped high-dose configuration for proton therapy (PT). This approach allows one to intensify target volume dose coverage for targets encompassing a critical, dose-limiting structure - like here, the cauda equina -, whilst delivering minimal dose to other healthy structures surrounding the target, thereby reducing the integral dose. Methods and results: intensity-modulated PT methods (IMPT) for spot scanning were applied to create and deliver a donut-shaped high-dose configuration with protons, allowing treating > 75% of the target with at least 95% of the prescribed dose of 72.8 CGE, whilst restricting dose to the cauda equina to 60-65 CGE. Integral dose was lower by a factor of 3.3 as compared to intensity-modulated radiotherapy with photons (IMXT). Conclusion: IMPT and spot scanning ...
A promising drugtarget currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (a7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the a7nAChR has many properties that make it an attractive therapeutic target. The a7nAChR is a ligand gated ion channel that has particularly high permeability to Ca^2^+ and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The a7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling cascades and influence downstream processes...
This book examines the applications of Monte Carlo (MC) calculations in therapeutic nuclear medicine, from basic principles to computer implementations of software packages and their applications in radiation dosimetry and treatment planning. It is written for nuclear medicine physicists and physicians as well as radiation oncologists, and can serve as a supplementary text for medical imaging, radiation dosimetry and nuclear engineering graduate courses in science, medical and engineering faculties. With chapters is written by recognised authorities in that particular field, the book covers the entire range of MC applications in therapeutic medical and health physics, from its use in imaging prior to therapy to dose distribution modelling targeted radiotherapy. The contributions discuss the fundamental concepts of radiation dosimetry, radiobiological aspects of targeted radionuclide therapy and the ...
This study emphasizes the need for a systematic and in-depth connection between the progress in quantum theory of energetic ion collisions and applications to hadron therapy. Scattering theory for fast ion beams has reached its stage of development where accurate and robustly applicable methodologies can advantageously be exported to applied fields such as space research, fusion energy program, medicine, etc. In particular, distorted wave collision theories at high energies readily provide total, partial and fully differential cross sections for inelastic collisions of ionic projectiles with any target system. By numerous and thorough testings, such theoretical cross sections were found to exhibit excellent agreement with experimental data on atomic targets. Adequate extensions of these me...
Antibodies directed against markers on cancer cells are gaining in importance for the purpose of targeting diagnostic and therapeutic agents. In the past, this approach has had very limited success principally because the classical methods for producing antibodies from blood serum of animals immunized with cancer cells or extracts were unsatisfactory. The situation has changed dramatically since 1975 following the design of procedures for 'immortalizing' antibody-producing cells (lymphocytes) by fusing them with cultured myeloma cells to form hybridomas which continuously secrete antibodies. Since these hybridomas produce antibodies coded for by a single antibody-producing cell, the antibodies are called monoclonal. Building on these advances in biomedical research, it is now possible to reproducibly manufacture monoclonal antibodies on a scale suitable for use in cancer detection and therapy.
9-cis-UAB30 is a potential chemopreventative agent that has been shown to be effective on many different types of tumors. The safety and toxicity of 9-cis-UAB30 had not been previously established. These studies were conducted to evaluate the potential toxicity and pharmacokinetics in a rodent and a nonrodent species for the purpose of investigational new drug submission. Oral gavage administration of 9-cis-UAB30 at the doses 0, 3, 15, and 100 ?mg/kg/day to CD? rats for 28 days showed a dose-dependent (although not dose-proportional) increase in plasma drug levels in week 4. The liver was the target organ for toxicity of 9-cis-UAB30. Hepatomegaly along with increases in serum aspartate-aminotransferase and alkaline-phosphatase levels were seen in rats. Moderate hypoalbuminemia and hyperglo...
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Caffeine and related xanthines were identified as potent stimulators for the bacterial cellulose production in A. xylinum. These compounds are present in several plants whose infusions are useful as culture-medium supplements for this acetobacterium. The proposed target for these native purine-like inhibitory substances is the novel diguanyl nucleotide phosphodiesterase(s) that participates in the bacterial cellulogenic complex.
Summary DNA topoisomerases are the key enzymes involved in carrying out high precision DNA transactions inside the cells. However, they are detrimental to the cell when a wide variety of topoisomerase-targeteddrugs generate cytotoxic lesions by trapping the enzymes in covalent complexes on the DNA. The discovery of unusual heterodimeric topoisomerase I in kinetoplastid family added a new twist in topoisomerase research related to evolution, functional conservation and their preferential sensitivity to Camptothecin. On the other hand, structural and mechanistic studies on kinetoplastid topoisomerase II delineate some distinguishing features that differentiate the parasitic enzyme from its prokaryotic and eukaryotic counterparts. This review summarizes the recent advances in research in kin...
The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.
The photocytotoxic effect of hypericin (Hyp) targeted by two different delivery techniques, namely, liposomes and anti-hepatocyte specific antigen (anti-HSA) was investigated. Optical absorption and steady-state fluorescence were used to analyze the conjugation of Hyp with anti-HSA model and to evaluate the encapsulation capacity and drug release in a liposome model. Particle size and thermal analysis of the prepared liposomes were performed using laser-light scattering and differential scanning calorimetry (DSC), respectively. Viability study of HepG2 cells exposed to Hyp in the two delivery systems, in the dark and following visible light irradiation, was performed in comparison to free Hyp. The intracellular uptake and localization of Hyp in HepG2 cells were analyzed by means of spectro...
Gonadal function was studied in two groups of children previously treated for medulloblastoma with surgery followed by postoperative craniospinal irradiation. In group 1 but not in group 2, the children also received adjuvant chemotherapy for one to two years. All children in group 1 received a nitrosourea (BCNU or CCNU), plus vincristine in four and procarbazine in three patients. The nine children in group 1 showed clinical and biochemical evidence of gonadal damage with elevated serum FSH concentrations and, in the boys, small testes for their stage of pubertal development. In group 2 (n . 8), each child had completed pubertal development normally, the boys had adult sized testes and the girls regular menses. Gonadotropin values were normal in all eight children. We conclude that nitrosoureas were responsible for the gonadal damage in the children in group 1, with procarbazine also contributing to the damage in the three children who received this drug. In view ...
Vulnerability to abused drugs is influenced by multiple genes unique to each drug as well as to risk genes for polydrug abuse. If several inbred mouse strains respond to different drugs similarly,...Full Text Available
Boron neutron capture therapy (BNCT) trials for human glioma (glioblastoma multiform) were initiated September 1994 at the Brookhaven National Laboratory (BNL). Patients are given p-boronophenylalanine-fructose (BPA-F) intravenously as the boron carrier followed by exposure to the epithermal-neutron beam at the Brookhaven Medical Research Reactor (BMRR). The initial phase of the study is to determine safety and toxicity of the drug and irradiation procedure. The epithermal-neutron beam was developed in a joint effort by BNL and Idaho National Engineering Laboratory (INEL) researchers. For the human trials, treatment planning and radiation dose estimation is performed using the BNCT-Rtpe and the rtt-MC computer codes developed by the INEL BNCT program. This paper discusses our initial experience using these treatment planning codes for human subjects. The basic principles of BNCT have been previously documented.
Tumour necrosis factor-alpha (TNF-?) antagonist drugs have been associated with increased risk of tuberculosis (TB). Tuberculin skin test (TST) is the most frequently used tool for identification of latent TB infection. We herein aimed to analyse the effect of TNF-? antagonists on the TST responses in a prospective study. The study group consisted of 182 patients (99 female, 83 male) who received TNF-? antagonists for various rheumatic disorders. All patients were evaluated with TST along with other parameters on the day of referral and on the 12th month visit. For those patients with a response of <5?mm induration at the initial evaluation, the TST was repeated to observe the booster effect. Out of 182 patients, 87 patients (48%) had a negative (0?4?mm) and 95 (52%) had a positive (?5?mm)...
The growing epidemic of juvenile obesity has prompted pediatricians to investigate obesity-related conditions in obese teenagers. We report a clinical case of severe hepatic fibrosis in an adolescent with severe and recent obesity. Because of elevated serum aminotransferase levels, abnormal hepatic ultrasonography and insulin resistance (impaired glucose tolerance), we suspected nonalcoholic steatohepatitis (NASH). Disease activity and fibrosis were confirmed on liver biopsy. Considering the risk of progression toward cirrhosis and its complications, and the pathological liver lesions, we started long-term medical monitoring and drugtherapy to control weight loss. At present, although biopsy is the only validated way to establish the diagnosis of NASH, there is no consensus on its indicat...
Patients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic patients and has been shown to improve survival and reduce incidence of adverse events. The current manuscript provides an overview of randomised controlled trials investigating the effect of IGL. Furthermore, systematic glucose?insulin?potassium infusion (GIK) has been studied to improve outcome after AMI. In spite of positive findings in some early studies, GIK did not show any beneficial effects in recent clinical trials and thus this concept has been abandoned. While IGL targeted to achieve normoglycaemi...
Purpose: The aim of this study was to assess interinstitutional variations in planning for stereotactic body radiation therapy (SBRT) for lung cancer before the start of the Japan Clinical Oncology Group (JCOG) 0403 trial.Methods and Materials: Eleven institutions created virtual plans for four cases of solitary lung cancer. The created plans should satisfy the target definitions and the dose constraints for the JCOG 0403 protocol.Results: FOCUS/XiO (CMS) was used in six institutions, Eclipse (Varian) in 3, Cadplan (Varian) in one, and Pinnacle3 (Philips/ADAC) in one. Dose calculation algorithms of Clarkson with effective path length correction and superposition were used in FOCUS/XiO; pencil beam convolution with Batho power law correction was used in Eclipse and Cadplan; and collapsed co...
Infrainguinal peripheral occlusive disease is increasingly being treated by endovascular techniques. Bare metal stainless steel, self-expanding nitinol stents, drug-eluting and covered stents (stent grafts) are becoming increasingly more important adjuncts to percutaneous translumninal angioplasty in the treatment of peripheral artery disease. In this article the available evidence supporting the use of stents in the femoropopliteal and tibial arteries will be described as well as their limitations. Future stent developments will also be discussed. (orig.) [German] Die endovaskulaere Therapie spielt bei der Therapie der peripheren arteriellen Verschlusskrankheit (PAVK) eine wichtige Rolle. Unbeschichtete ballonexpandierbare Stahlstents, selbstexpandierende Nitinolstents sowie medikamentenbeschichtete und ''covered stents'' (Stentgrafts) haben eine zunehmende Bedeutung als Zusatztherapie ...
In 1981, the German Society of Pediatric Oncology initiated a multi-institutional study for the treatment of Ewing's sarcoma. The protocol (Cooperative Ewing's Sarcoma Study, CESS 81) consisted of four courses of a four-drug-regimen (VACA), each course taking nine weeks. Local therapy (radical surgery or resection plus irradiation or radiotherapy alone) was performed after the second course. The results of CESS 81 can be summarized as follows: VACA-chemotherapy is effective in controlling systemic disease. Initial tumor mass and response to initial chemotherapy are of major prognostic value for local control and survival. Permanent local control is a problem, especially in irradiated patients. The high local failure rate in irradiated patients in CESS 81 could be attributable to the following reasons: Late start of local therapy (after 18 weeks of chemotherapy), uneven distribution of prognostic parameters: Large tumors ...
Hematopoietic stem cells (HSCs) have remained at the forefront of stem cell research for the past 50 years, since the therapeutic potential of bone marrow transplantation was realized. Uniquely, among stem and progenitor cells, research progress has been made in parallel between the laboratory benchtop and hospital bedside during this period. Integral to this work has been the role of the transfusion medicine services in the collection, storage, and processing of HSCs. The next decade promises to bring further developments: with new fields of cellular therapies, stem cell vaccination, and stem cell drug testing opening up. This article summarizes exciting areas of research concerning the behavior and potential clinical applications of HSCs. For the purposes of clarity, we describe in turn the trafficking and transfer of HSCs; ex vivo expansion of HSC units from different sources; and finally, applications of specifically selected subsets of ...
Therapeutic effect of p-aminobenzoic acid-N-xyloside Na (K-247) were studied. Eleven patients with a variety of solid tumors were treated with K-247 alone. K-247 was given orally 800 mg daily for 4 weeks. As for side effect of the drug, only mild gastritis was observed in a few patients. Partial response (over 25% reduction of tumor size) with a median duration of two months was observed in 3 patients. These cases were metastatic tumor of lung from the carcinoma of thyroid, metastatic tumors of lung from the carcinoma of kidney, and mediastinal tumor. In eight patients the response was classified as no change and in one patient there was progressive disease. Thus K-247 has some therapeutic activity in patients with solid tumor. Combination therapy of irradiation and administration of K-247 were also studied. In the twelve patients receiving the combination therapy, partial response was observed in 7 patients with complete ...
The purpose of this study was to compare 2 adaptive radiotherapy strategies with helical tomotherapy. A patient having mesothelioma with mediastinal nodes was treated using helical tomotherapy with pretreatment megavoltage CT (MVCT) imaging. Gross tumor volumes (GTVs) were outlined on every MVCT study. Two alternatives for adapting the treatment were investigated: (1) keeping the prescribed dose to the targets while reducing the dose to the OARs and (2) escalating the target dose while maintaining the original level of healthy tissue sparing. Intensity modulated radiotherapy (step-and-shoot IMRT) and 3D conformal radiotherapy (3DCRT) plans for the patient were generated and compared. The primary lesion and nodal mass regressed by 16.2% and 32.5%, respectively. Adapted GTVs and reduced plan...
A novel compact CT-guided intensity modulated proton radiotherapy (IMPT) system is described. The system is being designed to deliver fast IMPT so that larger target volumes and motion management can be accomplished. The system will be ideal for large and complex target volumes in young patients. The basis of the design is the dielectric wall accelerator (DWA) system being developed at the Lawrence Livermore National Laboratory (LLNL). The DWA uses fast switched high voltage transmission lines to generate pulsed electric fields on the inside of a high gradient insulating (HGI) acceleration tube. High electric field gradients are achieved by the use of alternating insulators and conductors and short pulse times. The system will produce individual pulses that can be varied in intensity, energy and spot width. The IMPT planning system will optimize delivery characteristics. The system will be capable of being sited in a conventional linac vault ...
Colorectal carcinoma is a highly prevalent and common cause of cancer in Taiwan. There is still no available cure for this malignant disease. To address this issue, we applied the multimodality of molecular imaging to explore the efficacy of diagnostic and therapeutic nanoradiopharmaceuticals in an animal model of human colorectal adenocarcinoma [colorectal cancer (CRC)] that stably expresses luciferase (luc) as a reporter. In this study, an in vivo therapeutic efficacy evaluation of dual-nanoliposome (100 nm in diameter) encaged vinorelbine (VNB) and "1"1"1In-oxine on HT-29/luc mouse xenografts was carried out. HT-29/luc tumor cells were transplanted subcutaneously into male SCID mice. Multimodality of molecular imaging approaches including bioluminescence imaging (BLI), gamma scintigraphy, whole-body autoradiography (WBAR) and in vivo tumor growth tracing, histopathology and biochemistry/hematology analyses were applied on xenografted SCID mice to study the treatments with 6% ...
Dyspnea is the most distressing symptom experienced by those suffering from advanced stages of chronic obstructive pulmonary disease (COPD). Activity-related dyspnea in COPD is multifactorial but is associated with increased central neural drive, impaired dynamic respiratory mechanics and abnormal respiratory muscle function. Each of these components can potentially be targeted for pharmacotherapy. Recent advances in the pharmacotherapy of COPD include the development of new long-acting bronchodilators which, when combined, provide sustained improvements in dyspnea. Additionally, novel applications of older therapies such as opiates, furosemide, helium-oxygen, and statins show early promise as dyspnea-relieving interventions in COPD. Effective pharmacological manipulation of the affective ...
HT-29 human colon tumor cells growing as spheroids have been evaluated as a model system for measuring the response of human colon tumor cell to antineoplastic agents. HT-29 cells have been capacity to form spheroids up to 1 mm or more in diameter when grown in spinner culture. The multicellular HT-29 spheroids develop hypoxic centers reflecting the cellular conditions found in human cancer treatment, i.e., nutritionally deficient hypoxic cells that are felt to be a significant source of both radiation and chemotherapy clinical treatment failures. Spheroids of increasing size were radiated and then dispersed into single cells for colony survival assay. Compared with irradiated single cell suspensions, the spheroid cells demonstrated a significant increase in radioresistance. Growing spheroids developed a complex radiation survival curve which was variable with respect to size of the spheroid. The drug 5-Fu was studied to examine in a preliminary fashion its ...
... or she will start intensive rehabilitation. This includes physical therapy and occupational therapy. Physical and occupational therapies aim at strengthening the remaining ...
There has been a major interest in the drug treatment of osteoporosis and an increase in the number of drugs available in most countries. The ideal drug (one which increases or restores bone density...Full Text Available
Convection-enhanced drug delivery (CED) is a novel approach to delivering drugs into brain tissue. Drugs are delivered continuously via a catheter, enabling large volume distributions of high drug concentrations...Full Text Available
In radiation therapy with hadron beams, conformal irradiation to a tumour can be achieved by using the properties of incident ions such as the high dose concentration around the Bragg peak. For the effective utilization of such properties, it is necessary to evaluate the volume irradiated with hadron beams and the deposited dose distribution in a patient's body. Several methods have been proposed for this purpose, one of which uses the positron emitters generated through fragmentation reactions between incident ions and target nuclei. In the previous paper, we showed that the maximum likelihood estimation (MLE) method could be applicable to the estimation of beam end-point from the measured positron emitting activity distribution for mono-energetic beam irradiations. In a practical treatment, a spread-out Bragg peak (SOBP) beam is used to achieve a uniform biological dose distribution in the whole target volume. ...
Purpose: The aim of this study was to assess interinstitutional variations in planning for stereotactic body radiation therapy (SBRT) for lung cancer before the start of the Japan Clinical Oncology Group (JCOG) 0403 trial. Methods and Materials: Eleven institutions created virtual plans for four cases of solitary lung cancer. The created plans should satisfy the target definitions and the dose constraints for the JCOG 0403 protocol. Results: FOCUS/XiO (CMS) was used in six institutions, Eclipse (Varian) in 3, Cadplan (Varian) in one, and Pinnacle3 (Philips/ADAC) in one. Dose calculation algorithms of Clarkson with effective path length correction and superposition were used in FOCUS/XiO; pencil beam convolution with Batho power law correction was used in Eclipse and Cadplan; and collapsed cone convolution superposition was used in Pinnacle3. For the target volumes, the overall coefficient of variation was 16.6%, and the ...
Abstract Many solute carrier transporters that interact with anticancer agents and contribute to their pharmacokinetics have been shown to be differentially upregulated in cancer cells as a result of adaptive response to altered nutritional requirements. This review focuses on pathophysiological function of membrane transporters responsible for the influx of physiological substances including oligopeptides, amino acids, and organic cations and anions, and summarizes the recent knowledge regarding mechanisms in their gene expressions. Broad substrate specificity of enhanced oligopeptide H+/peptide cotransporter 1 activity in cancer cells is useful for tumor tissue-specific delivery of chemotherapeutic agents and positron emission tomography diagnostic probes. Amino acid transporters such as...
Abstract:- Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn-s disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn-s disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and t...
The present study was carried out to exploit the feasibility of using polymeric nanosponges as an alternative carrier for targeting econazole nitrate (EN) to the skin through topical hydrogel formulation. Nanosponges prepared by emulsion solvent diffusion method were evaluated for various physicochemical parameters and in vitro drug release. The nanosponges of EN were discrete free flowing nanosized particles with perforated orange peel like morphology as visualized by SEM. The nanosponge formulated using PVA:EC (3:2) displayed highest in vitro release after 12 ?h in phosphate buffer (pH 6.8) that fitted matrix model. Selected nanosponge was formulated as Carbopol 934 NF hydrogel using varying concentrations of permeation enhancers propylene glycol and N-methyl-2-pyrrolidone. The EN nanosp...
The recent breakthrough in the generation of rat embryonic stem cells (rESCs) opens the door to application of gene targeting to create models for the study of human diseases. In addition, the in vitro differentiation system from rESCs into derivatives of three germ layers will serve as a powerful tool and resource for the investigation of mammalian development, cell function, tissue repair, and drug discovery. However, these uses have been limited by the difficulty of in vitro differentiation. The aims of this study were to establish an in vitro differentiation system from rESCs and to investigate whether rESCs are capable of forming terminal-differentiated cardiomyocytes. Using newly established rESCs, we found that embryoid body (EB)-based method used in mouse ESC (mESC) differentiation...
Adipose tissue plays an essential role in energy homeostasis as a metabolic and endocrine organ. Accordingly, adipocytes are emerging as a major drugtarget for obesity and obesity-mediated metabolic syndrome. Dysfunction of enlarged adipocytes in obesity is involved in obesity-mediated metabolic syndrome. Adipocytokines, such as adiponectin released from small adipocytes, are able to prevent these disorders. In this study, we found that honokiol, an ingredient of Magnolia officinalis used in traditional Chinese and Japanese medicines, enhanced adipocyte differentiation in 3T3-L1 preadipocytes. Oil Red O staining showed that treatment with honokiol in the presence of insulin dose-dependently increased lipid accumulation in 3T3-L1 preadipoyctes although its activity was weak compared with r...
Nano-sized silica is a promising material for disease diagnosis, cosmetics and drugs. For the successful application of nano-sized material in bioscience, evaluation of nano-sized material toxicity is important. We previously found that nano-sized silica particles with a diameter of 70nm showed acute liver failure in mice. Here, we performed histological analysis of major organs such as the liver, spleen, lung, kidney, brain and heart in mice, chronically injected with 70-nm silica particles for 4weeks. Histological analysis revealed hepatic microgranulation and splenic megakaryocyte accumulation in these 70-nm silica particles treated mice, while the kidney, lung, brain and heart remained unaffected. Thus, liver and spleen appear to be the major target organs for toxicity by the chronic a...
From 1981 up to February 1985, a total of 93 protocol patients entered the study CESS 81. The protocol recommended an initial 18-week period of polychemotherapy (VACA) followed by local therapy and two additional cycles of chemotherapy. Local therapy consisted either of radical surgery or of incomplete resection plus postoperative irradiation with 36 Gy or of radiotherapy alone (46 and 60 Gy). Centrally located lesions were always irradiated with 60 Gy. This article summarizes the data after 5 years. Data of 93 patients were analysed in October 1986 after a median follow-up of 37 months. The projected 5-year survival is 50%. The relapse rate was 42%, distant relapses occurred in 19%, local (plus distant) relapses in 23%. Most of the relapses occurred during the first 3 years of observation. Failure rate was high in patients undergoing irradiation alone (44%). Initial tumour mass (> 100 ml) and histopathologic response to initial chemotherapy ...
A technique capable of measuring the electron energy fluence spectra in a scattering medium was designed. These measurements were performed by setting a bremsstrahlung conversion target on the surface of a phantom, at an intermediate depth, and at a depth equal to electron mean range. The bremsstrahlung produced by the deceleration of electrons in the target was passed through an air channel in the phantom and passed forward by a pinhole collimator into a Na(Tl) detector. The measured pulse height data were unfolded to correct for the distortion of the spectrometer system by using the FORIST unfolding code. The unfolded bremsstrahlung spectra represent the electron energy fluence spectra convolution with the bremsstrahlung produced in the target. To generate the electron energy fluence spectra, the unfolded bremsstrahlung spectra were deconvoluted by using the MAZE2 unfolding code. CYLTRAN, a coupled electron-photon Monte ...
BACKGROUND AND PURPOSE Human K2P3.1 (TASK1) channels represent potential targets for pharmacological management of atrial fibrillation. K2P channels control excitability by stabilizing membrane potential and by expediting repolarization. In the heart, inhibition of K2P currents by class III antiarrhythmic drugs results in action potential prolongation and suppression of electrical automaticity. Carvedilol exerts antiarrhythmic activity and suppresses atrial fibrillation following cardiac surgery or cardioversion. The objective of this study was to investigate acute effects of carvedilol on human K2P3.1 (hK2P3.1) channels. EXPERIMENTAL APPROACH Two-electrode voltage clamp and whole-cell patch clamp electrophysiology was used to record hK2P3.1 currents from Xenopus oocytes, Chinese hamster o...
The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and ?-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two ...
Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. ...
Neurotensin (NT) and its high affinity receptor (NTR1) are involved in several neoplastic processes. Thus, NT-based radiopharmaceuticals are potential tracers for targeted diagnosis and therapy of NTR-positive tumours. A new analogue based on NT(8-13), NT-XIX, with the three enzymatic cleavage sites stabilised, was synthesised and tested. The synthesis was performed by Boc strategy. Labelling with "9"9"mTc/"1"8"8Re was performed using the tricarbonyl technique. Metabolic stability was tested in vitro and in vivo. NT-XIX was further characterised in vitro in HT-29 cells and in vivo in nude mice with HT-29 xenografts. NT-XIX showed much longer half-lives than non-stabilised analogues. Binding to NTR1 was highly specific, although the affinity was lower than that of natural NT. Bound activity rapidly internalised into HT-29 cells and 50% remained trapped after 24 h. In the time-course biodistribution, the highest uptake was found in the tumour at ...
In the treatment of prostatic cancer using a newly proposed intermittent multiportal therapy (DIMT), acute reactions, change in tumor marker levels, and complications more than 6 months after treatment were evaluated. From June 1989 to September 1990, 26 patients with prostatic cancer (stage A2, 3 patients; B, 9; C, 2; D, 10; recurrence, 2) were treated. Fifteen patients were followed up for more than one year, with a mean period of 11.6 months. The treatment schedule is 52.5 Gy in 16 fractions in 4 weeks for radical treatment, and 30.0 Gy in 8 fractions in 2 weeks for palliative treatment. The 360 degree rotation about the patient was divided into 16 fractions, and 2 opposing fractions were used in one day as parallel opposed portals to treat the target volume. The fractions were serially treated one per day, so that 8 treatment days produced a total dose of distribution similar to that for conventional conformational ...
The interest for medicinal plants has raised again in the last decades, after overcoming a declination period caused by the advances in the researches and development of the synthetic drugs industries. This growing interest has been stimulated mainly by searching cheap and accessible alternative therapies. However, in order to have natural products based treatment in an efficient and safety way, it is necessary to guarantee the plant authenticity, finding adulterations and to assure a low level of microbiological contaminations to avoid damages to consumer's health. The decontamination method should be chosen for eliminating or reduce the microorganisms level without loss of the plant active constituents that would destroy its therapeutic action. At the present work, the possibility of using #gamma# and X electromagnetic radiations to sterilize a Brazilian medicinal plant (Maytenus aquifolium Martius, Celastraceae), which shows anti-ulcer ...
OBJECTIVE:- Tumor necrosis factor (TNF) inhibitors can be used to treat inflammatory bowel disease (IBD) but may lead to anti-nuclear antibody (ANA) positivity and lupus-like reactions. Because of its unique structure, certolizumab has lower rates of these complications. We sought to investigate whether patients who have had lupus-like reactions to infliximab or adalimumab would be able to tolerate certolizumab. METHODS:- We performed a retrospective analysis on the 23 patients at the Roberts Inflammatory Bowel Disease Center who received certolizumab for the treatment of Crohn's disease from March 2008 to June 2009. We identified 6 patients who were switched to this drug because of lupus-like reactions from prior anti-TNF therapy and had documented ANA after the reaction and prior to cert...
Background and purpose: the recent RTOG guidelines for future clinical developments in gynecologic malignancies included the investigation of dose escalation in the paraaortic (PO) region which is, however, very difficult to target due to the presence of critical organs such as kidneys, liver, spinal cord, and digestive structures. The aim of this study was to investigate intensity-modulated radiotherapy's (IMRT) possibilities of either increasing, in a safe way, the dose to 50-60 Gy in case of macroscopic disease or decreasing the dose to organs at risk (OR) when treatment is given in an adjuvant setting. Material and methods: the dosimetric charts of 14 patients irradiated to the PO region at the department of radiation oncology, university hospital of Liege, Belgium, in 2000 were analyzed in order to compare six-field conformal external-beam radio-therapy (CEBR) and five-beam IMRT approaches. Both CEBR and IMRT investigations were planned to ...
Megavoltage photon intensity-modulated radiation therapy (IMRT) is typically used in the treatment of prostate cancer at our institution. Approximately 1% to 2% of patients with prostate cancer have hip prostheses. The presence of the prosthesis usually complicates the planning process because of dose perturbation around the prosthesis, radiation attenuation through the prosthesis, and the introduction of computed tomography artifacts in the planning volume. In addition, hip prostheses are typically made of materials of high atomic number, which add uncertainty to the dosimetry of the prostate and critical organs in the planning volume. When the prosthesis is bilateral, treatment planning is further complicated because only a limited number of beam angles can be used to avoid the prostheses. In this case study, we will report the observed advantages of using noncoplanar beams in the delivery of IMRT to a prostate cancer patient with bilateral hip prostheses. The ...
Electron beam therapy of lesions such as cutaneous metastatic carcinoma and reticulum cell sarcoma is performed via multiple portals for a wide irradiation field. However, the dose distribution in border areas is generally uneven, resulting in hot and cold dose areas depending on the intervals of the portals. We performed electron irradiation by the pendulum technique, especially on curved areas, and evaluated the technique in various respects. Pendulum electron beam irradiation is indicated when the length of the cone must be reduced in order to deliver the target volume near the skin surface as well as to avoid the occurrence of hot spots deep in the body. We prepared a 15cm rotating cone by cutting a 30cm fixed irradiation cone. The modification posed no disadvantages in terms of extent and flatness of the beam, or stability during rotation. After determining the relationship between the rotation speed and the dose, the technique was ...
The field of stem cell research was revolutionized with the advent of induced pluripotent stem cells. By reprogramming somatic cells to pluripotent stem cells, most ethical concerns associated with the use of embryonic stem cells are overcome, such that many hopes from the stem cell field now seem a step closer to reality. Several methods and cell sources have been described to create induced pluripotent stem cells and we discuss their characteristics in terms of feasibility and efficiency. From these cells, cardiac progenitors and cardiomyocytes can be derived by several protocols and most recent advances as well as remaining limitations are being discussed. However in the short time period this technology has been around, evidence emerges that induced pluripotent stem cells may be more prone to genetic defects and maintain an epigenetic memory and thus may not be entirely the same as embryonic stem cells. Despite the lack of a complete fundamental understanding of stem cell biology, ...
It may be necessary to reduce microbiological contamination of crude drugs (medicinal plants or their parts like roots, leaves, flowers). This can be done by treating the drugs with ionizing radiation. Meethods for detection of such an irradiation were developed. It could be pointed out that measurements of luminescence, viscosity and electron spin resonance were suitable for specific drugs, but not for all drugs. (orig.).
Abstract Male infertility continues to be a clinical challenge of increasing significance. While male factors such as decreased semen quality are responsible for 25% of all infertility issues, the etiology of suboptimal semen quality is poorly understood. Many physiological, environmental, and genetic factors have been implicated, including oxidative stress. Oxidative stress is induced by reactive oxygen species (ROS), or free radicals, and although ROS are required for critical aspects of sperm function, excessive levels of ROS can negatively impact sperm quality. The origin of ROS generation, and the etiologies of increased ROS in men with suboptimal sperm quality have only recently been elucidated, offering multiple targets for potential therapy. Here, we present a critical review of th...
Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanisms that target cancer cells and regulate tumor microenvironment is essential in designing anticancer therapies. Here, we showed that serum amyloid-A (SAA) and cathelicidin (LL-37) stimulated M-CSF and MCP-1 expression with or without lipopolysaccharide (LPS) administration; conversely, lipoxin-A4 (LXA4) and annexin-A1 (ANXA1) inhibited LPS-induced M-CSF and MCP-1 production by human (HepG2) and mouse (H22) hepatocellular carcinoma cells (HCCs). The effects of LXA4, ANXA1, SAA ...
Positron emission tomography (PET) is the gold standard for non-invasive assessment of myocardial viability and allows accurate detection of coronary artery disease by assessment of myocardial perfusion. Magnetic resonance imaging (MRI) provides high resolution anatomical images that allow accurate evaluation of ventricular structure and function together with detection of myocardial infarction. Potential hybrid PET/MR tomography may potentially facilitate the combination of information from these imaging modalities in cardiology. Furthermore, the combination of anatomical MRI images with the high sensitivity of PET for detecting molecular targets may extent the application of these modalities to the characterization of atherosclerotic plaques and to the evaluation of angiogenetic or stem cell therapies, for example. This article reviews studies using MRI and PET in parallel to compare their performance in cardiac applications together with the ...
A computer-based beam dosimetry measurement system for boron neutron capture therapy provides accurate, sensitive, and rapid readout and recording of all beam dose components, epithermal and thermal neutron flux, and gamma-ray dose rate. This dosimetric system includes input from the characterization of the epithermal neutron beam developed at the Massachusetts Institute of Technology, actual BPA pharmacokinetic data from a specific human subject being irradiated, output of MacNCTPLAN, a treatment planning system developed by the authors group, and input from the five on-line beam detectors. The purpose of this system and associated readout systems is to ensure that the desired dose is delivered to the subject within acceptable dose tolerances, e.g., {+-}5% of the target dose, and that any perturbations in the neutron beam that may occur during irradiation can be rapidly evaluated and the appropriate measures taken.
A computer-based beam dosimetry measurement system for boron neutron capture therapy provides accurate, sensitive, and rapid readout and recording of all beam dose components, epithermal and thermal neutron flux, and gamma-ray dose rate. This dosimetric system includes input from the characterization of the epithermal neutron beam developed at the Massachusetts Institute of Technology, actual BPA pharmacokinetic data from a specific human subject being irradiated, output of MacNCTPLAN, a treatment planning system developed by the authors group, and input from the five on-line beam detectors. The purpose of this system and associated readout systems is to ensure that the desired dose is delivered to the subject within acceptable dose tolerances, e.g., #+-#5% of the target dose, and that any perturbations in the neutron beam that may occur during irradiation can be rapidly evaluated and the appropriate measures taken.
In Europe, the use of anti-EGFR monoclonal antibodies is restricted to Kirsten RAS (KRAS) wild-type colorectal tumors. Information on the KRAS status of the patients tumor is thus key for clinical practice; however, there is little guidance or definition on which KRAS mutations to assess and how to assess them. To ensure the consistency and the quality of KRAS test results in Europe, an interlaboratory control network needs to be set up. This pilot study aimed to identify the variables that need to be assessed in a quality control scheme and to provide a first assessment in a selected set of laboratories. Fourteen different tumor cases were circulated between 13 laboratories by a central laboratory acting as the referent for the mutation status determination. This study illustrated that of...
Radiolabeled lipiodol has been used for targeting liver cancer. We developed a lipiodol solution of {sup 188}Re-TDD (2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol) and investigated its feasibility for the treatment of liver cancer. The lipiodol solution of {sup 188}Re-TDD was well-retained in the lipiodol phase in vitro. After injection through the tail veins of mice, high lung-uptake was investigated which is evidence of embolizing activity. We also found high accumulation in hepatoma after injection through the hepatic arteries of hepatoma-bearing rats. In conclusion, the lipiodol solution of {sup 188}Re-TDD is a promising agent for liver cancer therapy.
The findings reported in this study highlight several important features of the development of hematopoietic stem cells after transplantation into irradiated recipients. First, they demonstrate the existence of a class of primitive multipotential stem cells that can function for a significant portion of the lifetime of a mouse (15 mo). In addition, they clearly show that these primitive stem cells can be infected with recombinant retroviruses and thus would be appropriate targets for gene therapy in somatic tissues. Second, our data indicate that the progeny of some, but not all, of the primitive stem cells have fully expanded into the various hematopoietic lineages by 2 mo after reconstitution. Finally, our analysis of the secondary recipients provides strong evidence suggesting that the primitive stem cell population can actually clonally expand. Our current experiments are aimed at determining the extent to which this expansion can occur and ...
A cross sectional study on the mineral density of the 3rd lumbar vertebral trabecular bone was carried out in 123 children less than 15 years old, comprising 44 controls, and 79 patients affected with conditions which are at risk for developing metabolic derangement of skeletal bone (34 patients taking antiepileptic drugs (AED), 29 undergoing glucocorticoid (GC) therapy and 16 bedridden patients), by using quantitative computed tomography (QCT) with a CaCO{sub 3} phantom. Serum Ca and alkaline-phosphatase (Alp) levels were measured at the time of QCT examinations in all. The results obtained were as follows: The QCT values in the control children showed neither age dependency nor a sexual difference before puberty. The QCT values in each group showed significant difference with one another; the control group>the AED group>the GC group>the bedridden group (p<0.05{approx}0.005). The serum Ca levels in each pathology group were ...
We aim to examine the spectrum of bacteria causing corneal infections and their antibiotic susceptibility patterns. This will serve as a guideline for empiric therapy of corneal infections. We conducted the study over a period of 18 months from March 2001 through December 2002 in King Abdul-Aziz University Hospital, Riyadh, Kingdom of Saudi Arabia. Corneal specimens taken from 200 patients were inoculated directly onto different types of media. The isolates were identified and then tested against the appropriate topical or systemic antibiotics. Sixty-seven (33.5%) of the total specimens were culture positive and 133 (66.5%) were culture negative. Fourteen (7%) of these showed organisms in the Gram stained smears and correlated well with the culture reports. Of the 67 positive cultures, 53 (79.1%) were Gram-positive bacteria mostly coagulase-negative Staphylococci 29 (43.3%) followed by Streptococcus pneumoniae (S. pneumoniae) 13 (19.4%). Among Gram-negative ...
A combination of sustained release (SR) naltrexone (32mg/day) and bupropion SR (360mg/day) plus behavioral counseling was evaluated for the treatment of smoking cessation and mitigation of nicotine withdrawal and weight gain. Thirty overweight or obese nicotine-dependent subjects were enrolled in a 24-week, open-label study; 85% and 63% completed 12 and 24weeks, respectively. The target quit date was Week 4. Week 4-12 continuous abstinence rate was 48%, 78% of subjects achieved CO 10ppm, serum cotinine decreased from 185 to 48mg/L, and tobacco use decreased from 129 to 14 cigarettes/week. Similar results were seen at Week 24. Body weight was essentially unchanged (Week 12: -0.1%; Week 24: +0.4%). Except for a transient significant increase 1week after the target quit date (p<0.05), nicotin...
A technique for delivering genes carried by recombinant retroviruses into specific cell types could have numerous applications in oncology, developmental biology, and gene therapy. As a first step toward this remote goal the authors designed a procedure allowing in vitro cell targeting by retroviruses. Biotinylated antibodies against the viral envelope protein on one side, and against specific cell membrane markers on the other side, were bridged by streptavidin and used to link the virus to the host. The method was successfully used to infect human cells with ecotropic murine retroviruses by means of major histocompatibility complex class I and class II antigens and appears easily adaptable to other cell, membrane markers. Moreover, the sequential protocol they design, although allowing infection of human cells, requires less stringent safety constraints than would handling of amphotropic virus stocks.
Abstract The authors provide a survey of how images are used in radiation therapy to improve the precision of radiation therapy plans, and delivery of radiation treatment. In contrast...Full Text Available
Nearly every drug may cause changes to ocular tissues through a variety of mechanisms. Medication overdoses, drug–drug interactions but also chronic administration of medications at...Full Text Available
BackgroundThere are no drugs presently available to treat traumatic brain injury (TBI). A variety of single drugs have failed clinical trials suggesting a role for drug combinations....Full Text Available
The sale of consumer products over the Internet has grown rapidly, including the sale of drugs. While the growth in online drug sales by reputable pharmacies is a trend that may provide benefits to...Full Text Available
BackgroundNonsteroidal anti-inflammatory drugs are commonly used to treat postoperative and chronic pain. Animal studies suggest these drugs act in part by blocking...Full Text Available
In rats, drug-induced depression of the central nervous system has been shown generally to be associated with an elevation in level of total acetylcholine in the brain. This generalization held true...Full Text Available
PURPOSE: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment thus requiring innovative and effective targetedtherapies. The oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates insulin-like growth factor binding protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function.EXPERIMENTAL DESIGN: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarray and real-time PCR and ELISA in human HCC cell lines. Dual Fluorescence in situ hybridization was performed to detect loss of heterozygosity at IGFBP7 locus. Stable IGFBP7-overexpressing clones were established in the background of AEG-1-overexpressing human HCC cells and were analyzed for in vitro proliferation and senescence and in vivo tumorigenesis and ...
Anticancer drug thyotepa (10 mg/ kg) hormonal compound thyroxine (40 mg / kg) and D3 vitamin (30,000 IU / kg) have been administrated simply or associated to Wistar rats bearing Walker carcinosarcoma. The chromatin (the complex of DNA and proteins from nuclei) has been extracted from Walker tumor and submitted to fast neutron beams produced by deuterons (13 MeV) on thick Be target at an IPNE U-120 Cyclotron, in doses of 5-100 Gy. Thermal transition of chromatin fluorescence intensity of chromatin-ethidium bromide complexes and intrinsic fluorescence of chromatin have been analysed. Association of thiotepa with thyroxine and D3 vitamin produced a diminution of chromatin lesions induced by the cytostatic. Thus in the effects of fast neutrons radiolysis in chromatin significant differences occurred. These results could help to improve the methodology of associated chemotherapy-radiotherapy in clinical applications. (author).
The magnetic separation technology using sub-microsized ferromagnetic particle is indispensable in many areas of medical biosciences. For example, ferromagnetic particles (200-500 nm) are widely used for cell sorting in stem cell research with the use of cell surface-specific antigens. Nanosized ferromagnetic particles (10-20 nm) have been suggested as more suitable in drug delivery studies given their efficiency of tissue penetration, however, the magnetic separation method for them has not been established. One of the major reasons is that magnetic force acting on the object particles decreases drastically as a particle diameter becomes small. In this study, magnetic force acting on the targets was enhanced by the combination of superconducting magnet and the filter consisting of ferromagnetic particle. By doing so, we confirmed that Fe{sub 3}O{sub 4} of 20 nm in diameter was trapped in the magnetic filter under an external magnetic field of ...
Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review discusses three exposure scenarios involving acetylcholine systems: nicotine from maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three have long-term, adverse effects on specific processes involved in brain cell replication and differentiation, synaptic development and function, and ultimately behavioral performance. Many of these effects can be traced to the sequence of cellular events surrounding the trophic role of acetylcholine acting on its specific cellular receptors and associated signaling cascades. However, for chlorpyrifos, additional ...
Purpose: We present an update analysis of the multiinstitutional Ewing's sarcoma study CESS 86. Methods and Materials: From January 1986 through June 1991, 177 patients with localized Ewing's sarcoma of bone, aged 25 years or less, were recruited. Chemotherapy consisted of four 9-week courses of vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) in low-risk tumors (extremity tumors =# 100 cm"3). Local therapy was an individual decision in each patient and was either radical surgery (amputation, wide resection) or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractionation (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionated split-course irradiation simultaneously with the VACA/VAIA chemotherapy (twice daily 1.6 Gy, break of 12 days after 22.4 Gy and 44.8 Gy, total dose and ...
Background and purpose: the recent RTOG guidelines for future clinical developments in gynecologic malignancies included the investigation of dose escalation in the paraaortic (PO) region which is, however, very difficult to target due to the presence of critical organs such as kidneys, liver, spinal cord, and digestive structures. The aim of this study was to investigate intensity-modulated radiotherapy's (IMRT) possibilities of either increasing, in a safe way, the dose to 50-60 Gy in case of macroscopic disease or decreasing the dose to organs at risk (OR) when treatment is given in an adjuvant setting. Material and methods: the dosimetric charts of 14 patients irradiated to the PO region at the department of radiation oncology, university hospital of Liege, Belgium, in 2000 were analyzed in order to compare six-field conformal external-beam radio-therapy (CEBR) and five-beam IMRT approaches. Both CEBR and IMRT investigations were ...
Purpose: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and Methods: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing's sarcoma trials CESS 81 (recruitment period 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete ...
The authors have studied the distribution of H-3 labelled schistosomicidal drug in mice by autoradiography. The H-3-labelled substances were found in liver and kidney and in successfully decreasing amounts in brain, lung, heart, fat, testis, pancreas and spleen. In various cells the silver granules were present mainly in the cytoplasms but a few in the nucleus. After administration of this labelled schistosomicidal drug, the mice were killed and studied in groups successively at 4, 8, 24 hrs. No difference in the distribution of silver granules were observed. This fact indicated that, this drug was rapidly absorbed and highly concentrated with a long duration of reservation in liver. All of these favours the schistosomicidal effect of the drug. As this drug was highly concentrated in the cytoplasm of liver cells, that might provide a pathophysiologic basis for the explanation of ...
The incidence of hilar cholangiocarcinoma is very rare worldwide. Radical resection is the only prognostic factor for long survival in patients with hilar cholangiocarcinoma. Postoperative radiation therapy can improve local control and survival rates for patients with palliative resection, but it remains controversial in patients with radical resection. Biliary drainage can effectively release bile duct obstruction for the majority of patients with locally advanced disease, and may even prolong survival when combined with radiation therapy. Radiation therapy includes extrernal beam therapy alone, external beam therapy with intraluminal brachytheapy and new radiation technique, such as three dimentional conformal therapy and intensity modulated radiation therapy. The propective randomized clinical study is needed for further investigation in ...
Therapeutic hypothermia is a promising method for controlling intracranial pressure (ICP) in severely brain-injured patients. However, clinical data regarding the effect of brain hypothermia on overall outcome of these patients is limited. This may be because there are specific pitfalls associated with the clinical management of induced hypothermia in patients with severe traumatic brain injury (TBI). These pitfalls may be avoided by preventing specific risk factors when cooling is induced and with rewarming. However, these risk factors have not been well systematically discussed in the literature. In this paper, three categories of clinical issues regarding the management of brain hypothermia are discussed: (1) stress-induced secondary brain injury mechanisms; (2) technical aspects of intensive care unit (ICU) cooling management; and (3) rewarming rates and methods. For patients with a Glasgow Coma Scale (GCS) score of less than 8, management of stress-induced insulin-resistant ...
A method has been developed for calibration of CT-numbers to volumetric electron density distributions using tissue substitutes of known elemental composition and experimentally determined electron density. This information have been used in a dose calculation method based on photon and electron interaction processes. The method utilizes a convolution integral between the photon fluence matrix and dose distribution kernels. Inhomogeneous media are accounted for using the theorems of Fano and O'Connor for scaling dose distribution kernels in proportion to electron density. For clinical application of a calculated dose plan, a method for prediction of accelerator output have been developed. The methods gives the number of monitor units that has to be given to obtain a certain absorbed dose to a point inside an irregular, inhomogeneous object. The method for verification of dose distributions outlined in this study makes it possible to exclude the treatment related variance contributions, ...
Beams may be viewed as directed and focussed flow of energy and information, carried by particles and electromagnetic radiation fields (ie, photons). Often, they interact with each other (eg, in high energy colliders) or with other forms of matter (eg, in fixed targets, sychrotron radiation, neutron scattering, laser chemistry/physics, medical therapy, etc.). The whole art and science of beams revolve around the fundamental quest for, and ultimate implementation of, mechanisms of production, storage, control and observation of beams -- always directed towards studies of the basic structures and processes of the natural world and various practical applications. Tremendous progress has been made in all aspects of beam physics and technology in the last decades -- nonlinear dynamics, superconducting magnets and rf cavities, beam instrumentation and control, novel concepts and collider praradigms, to name a few. We illustrate this progress with a ...
A human cholangiocarcinoma, Ch-1, serially transplanted to nude mice was used for experimental chemotherapy, radiotherapy, and conbination chemoradiotherapy. In the group of chemotherapy with single drug, Mitomycin C (MMC) revealed greater effectiveness than Adriamycin in terms of tumor regression, histological findings, and minor side effects. MMC and radiotherapy by Linac X-ray showed exponential linear dose response curve against tumor weight. Their effects were equivalent at doses of MMC 1 mg/kg and radiation 1,000 rads/mouse in the changes of tumor weight and of histological findings which were similar to each other. Combination chemoradiotherapy showed the synergistic action when the radiation (500 rads/mouse) was performed before MMC (0.5 mg/kg) administration, whereas only the additive effect was observed when the sequence was reversed. The cell kinetic analysis was performed by the impulse cytophotometry, "3H-thymidine uptake labeling index (L.I.), and ...
Abstract in english Type II reaction in leprosy, or erythema nodosum leprosum (ENL), is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide (more) , can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, ...
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and ...
BackgroundTransarterial chemoembolization (TACE) therapy is an effective locoregional treatment in hepatocellular cancer (HCC) patients. For early modification of therapy, markers...Full Text Available
Forty-four patients with histologically proven Hodgkin's disease underwent initial treatment with extended-field radiation therapy. Nineteen of these patients also received combination chemotherapy....Full Text Available
The importance of intact host defense mechanisms for successful antimicrobial therapy was investigated in an animal model. Recovery from lobar pneumococcal pneumonia as a result of penicillin therapy...Full Text Available
Radionuclide bone metastases therapy is a major achievement of nuclear medicine. Development of less radiotoxic and more effective radiopharmaceuticals is therefore a challenge for radiopharmacists and industry. This paper reviews the application of rhenium-188 HEDP as a reactor- or generator-produced nuclide for bone metastases therapy. (author)
The current therapy for extrinsic and intrinsic asthma, together with that of ‘wheezing bronchitis’, is presented, with special attention to bronchodilators and adrenocorticosteroids....Full Text Available
PurposeTo determine the dosimetric impact of inter-fraction anatomical movements in prostate cancer patients receiving proton therapy.Full Text Available
1 Recommendations for correct therapy with digoxin from twenty-five sources are reviewed. 2 Some recommendations may be unsuitable for use with high bioavailability...Full Text Available
... radiation during clinical therapy and exposures due to radiation accidents or attacks, in which the doses are uncontrolled ... only be used off-label in victims of radiation accidents or attacks. The idea...
... Accession Number : ADB119274. Title : Transdermal Drug Delivery System. Stage 1. Volume 1. Descriptive Note : Final rept. 15 Aug 85-14 Oct 87,. ...
Sponges can provide potential drugs against many major world-wide occurring diseases. Despite the high potential of sponge derived drugs no sustainable production method has been developed. Thus far...Full Text Available
... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (139) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (115) Inhalants (12) K Ketamine (1) L LSD ( ...
... HIV & AIDS (15) I Infectious Diseases (22) Injection Drug Use (7) M Mental Illness (141) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (117) Inhalants (13) K Ketamine (1) L LSD ( ...
... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (139) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (112) Inhalants (12) K Ketamine (1) L LSD ( ...
... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (138) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (116) Inhalants (12) K Ketamine (1) L LSD ( ...
IntroductionResearch is an essential tool in facing the challenges of scaling up interventions and improving access to services. As in many other countries, the translation of research...Full Text Available
Multidrug-resistant tuberculosis is an increasing public health concern in many parts of the world, especially in low-income countries, where most cases occur. Traditional drug susceptibility testing...Full Text Available
A knowledge-based expert system has been developed to support human decision makers who assess drug products for inclusion in the Saskatchewan Formulary. Formulary inclusion and deletion decisions...Full Text Available
OBJECTIVES:To investigate the prevalence of potential drug interactions at the intensive care unit of a university hospital in Brazil and to analyze their clinical significance.METHODS:This...Full Text Available
The main aim of the present study was to evaluate potential of ternary complexation (comprising of drug, cyclodextrin and polymer) as an approach for taste masking. For this purpose famotidine with...Full Text Available
The evolution of drug resistant bacteria is a severe public health problem, both in hospitals and in the community. Currently, some countries aim at concentrating highly specialized services in large...Full Text Available
Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or “biological cutoffs,”...Full Text Available
Purpose of reviewPhysicians, researchers and policy makers must understand the myriad consequences of multidrug and extensively drug-resistant tuberculosis (TB) within...Full Text Available
Few data exist about the impact of computerized prescribing systems on outpatient medication errors (MEs) and adverse drug events (ADEs). We compared the rates of MEs and ADEs in handwritten sites versus...Full Text Available
The purpose of this study was to illuminate the experiences of poor, urban HIV-positive drug users. Sixty participants were asked about HIV risk behaviors, the impact of HIV on their lives,...Full Text Available
Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive....Full Text Available
Serum specimens obtained from a nationwide sample of parenteral drug abusers (PDAs) during the period 1971-72 had previously been screened for human immunodeficiency virus (HIV) antibodies. Some specimens...Full Text Available
The drug-binding properties of human alpha-foetoprotein (alpha FP) were investigated by a fluorescence-spectral method. Human alpha FP was shown to bind to albumin's site I marker (warfarin, phenylbutazone),...Full Text Available
ObjectivesWe undertook a meta-analysis to assess outcomes for drug-eluting (DES) and bare metal stents (BMS) in percutaneous coronary intervention (PCI) for unprotected...Full Text Available
Current methods for drug susceptibility testing of Mycobacterium tuberculosis are either costly or slow. As the prevalence of multidrug-resistant strains increases, the need for fast,...Full Text Available
Our understanding of the development of neurotransmitter systems in the central nervous system has increased greatly over the past three decades and it has become apparent that drug effects...Full Text Available
The regulation of gene expression in the brain reward regions is known to contribute to the pathogenesis and persistence of drug addiction. Increasing evidence suggests that the regulation of gene transcription...Full Text Available
BackgroundParticulate systems are well known to be able to deliver drugs with high efficiency and fewer adverse side effects, possibly by endocytosis of the drug carriers. On the...Full Text Available
BackgroundCancer stem cells (CSCs) have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with chemotherapeutic drugs, and/or...Full Text Available
The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the...Full Text Available
Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or “attack” phase to drive down transmission...Full Text Available
...treated for leukemia. B' s physician, who is employed by the HMO, is considering a treatment plan that includes six-mercaptopurine, a drug for treating leukemia in most children. However, the drug could be fatal if taken by a small percentage of...
... The pharmacologist/toxicologist and the statistician will jointly determine if a statistical review is needed and when the review should be done. ...
Boron Neutron Capture Therapy (BNCT) is a promising binary treatment modality for high-grade primary brain tumors (glioblastoma multiforme, GM) and other cancers. BNCT employs a boron-10 containing compound that preferentially accumulates in the cancer cells in the brain. Upon neutron capture by {sup 10}B energetic alpha particles and triton released at the absorption site kill the cancer cell. In order to gain penetration depth in the brain Fairchild proposed, for this purpose, the use of energetic epithermal neutrons at about 10 keV. Phase I/II clinical trials of BNCT for GM are underway at the Brookhaven Medical Research Reactor (BMRR) and at the MIT Reactor, using these nuclear reactors as the source for epithermal neutrons. In light of the limitations of new reactor installations, e.g. cost, safety and licensing, and limited capability for modulating the reactor based neutron beam energy spectra alternative neutron sources are being contemplated for wider ...
Full text: Radiotherapy treatment planning (RTP) relies heavily on medical imaging. Until recently, the most important planning tool was the treatment simulator. The kilovoltage radiographic capabilities in a treatment simulator enabled the boundaries of treatment fields to be visualized with respect to bony anatomic landmarks. Perhaps the most important advance in treatment planning in recent years is the ability to visualize the passage of the beams with respect to a more accurate geometrical representation of the tumor and other soft tissue structures. This 'virtual simulation' uses a computer-based representation of a patient to determine the extent of the disease and the location of radiation sensitive normal tissue. Computer tomographic (CT) imaging produces a high-resolution three-dimensional representation of anatomy that can be correlated with other image sets such as magnetic resonance images (MRI) of function. Positron emission tomographic (PET) imaging is beginning to be ...
Homidium bromide and isometamidium chloride are used extensively in the treatment of bovine trypanosomiasis in Africa, but no specific and sensitive method to detect the drug in plasma has been published yet. Comparing the methods of other investigators it was found that they could not overcome the protein binding of these drugs which reduced the available and determined drug to 10% of the real concentrations. These techniques overcome the protein binding by enzyme digestion and an alteration of the pH before adding the sample directly on clean-up columns. Drug recover rates above 80% were obtained. For the detection, the HPLC was employed using a C18 reversed phase analytical column and UV detection, determining both drugs as intact molecules. (author).
The aim of this study was to assess the feasibility of radiosterilization of drugs aqueous solutions and to evaluate the effects of some additives, such as mannitol, nicotinamide and pyridoxine, which might protect the drug from degradation. Metoclopramide was selected as a model drug. The structures of the degradation products were determined to gain insight on the radiolysis mechanisms in aqueous solution in order to design strategies to lower the drug degradation.Metoclopramide hydrochloride aqueous solutions with and without excipients were irradiated either with gamma rays or high-energy electrons. HPLC-DAD was used to measure the loss of chemical potency and to quantify the degradation products which were also characterized by LC-APCI-MS-MS. Metoclopramide recovery for gamma and elec...
The electroless nickel plating/poly(dl-lactide-co-glycolide) composite coating (EN-plating/PLGA composite coating) was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy AZ81 to double control the corrosion and drug release in the hanks' solution. The EN-plating was fabricated on the MAO coating to improve the corrosion resistance by overlaying most pores and micro-cracks on the surface of the MAO film. Meanwhile, a double layered organic poly(dl-lactide-co-glycolide)/paclitaxel (PLGA/PTX) drug releasing coating with a top layered PLGA drug controlled releasing coating on EN plating was prepared to control the drug release rate by adjusting the different lactide: glycolide (LA:GA) ratio of PLGA. Scanning electron microscopy (SEM) and the X-ray powder dif...
Radiation therapy has shown definite technical improvement due to application of proton beam irradiation. Clinical results of proton beam therapy also suggested enlargement of indication ranges in radial treatment and decrease of post radiation damages of the treatment of cancers in deep-seated organs. Inprovement of result in cancer therapy could be expected by this treatment technique in the future.
BackgroundTo compare two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the setting of hypofractionated...Full Text Available
This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal drug delivery compared ...
Radiotherapy can be very significant as the treatment for ocular lesions, eyes need to be preserved as properly as possible on their functions and cosmetics. The application of conventional X ray therapy has been gradually abandoned as conventional X ray therapy ceased to be accepted as the general treatment for malignant tumors. Consequently the necessity of electron beam therapy has been rising even as the substituted method for conventional X ray therapy. The department of radiology of Gunma University was obliged to establish a new therapy for ocular lesions, and has been trying electron beam therapy since 1973. It is concluded that electron beam therapy is not at all inferior to conventional X ray therapy as reported above. Basic therapeutic methods for ocular lesions are the following: 1) For epidermoid carcinoma, ...
Calcium-activated chloride channels (CaCCs) are widely expressed in mammalian tissues, including intestinal epithelia, where they facilitate fluid secretion. Potent, selective CaCC inhibitors have not been available. We established a high-throughput screen for identification of inhibitors of a human intestinal CaCC based on inhibition of ATP/carbachol-stimulated iodide influx in HT-29 cells after lentiviral infection with the yellow fluorescent halide-sensing protein YFP-H148Q/I152L. Screening of 50,000 diverse, drug-like compounds yielded six classes of putative CaCC inhibitors, two of which, 3-acyl-2-aminothiophenes and 5-aryl-2-aminothiazoles, inhibited by >95% iodide influx in HT-29 cells in response to multiple calcium-elevating agonists, including thapsigargin, without inhibition of calcium elevation, calcium-calmodulin kinase II activation, or cystic fibrosis transmembrane conductance regulator chloride channels. These compounds also inhibited ...
Endocrine disrupting chemicals can induce malformations and impairment of reproductive function in experimental animals and may have similar effects in humans. Recently, the environmental obesogen hypothesis was proposed, suggesting that environmental chemicals contribute to the development of obesity and insulin resistance. These effects could be related to chemical interaction with nuclear receptors such as the peroxisome proliferator activated receptors (PPARs). As several testosterone-reducing drugs are PPAR activators, we aimed to examine whether four PPAR agonists were able to affect fetal testosterone production and masculinization of rats. Additionally, we wished to examine whether these chemicals affected fetal plasma levels of insulin and leptin, which play important roles in the developmental programming of the metabolic system. Pregnant Wistar rats were exposed from gestation day (GD) 7-21 to diisobutyl phthalate (DiBP), butylparaben, ...
All microRNA (miRNA) target—finder algorithms return lists of candidate target genes. How valid is that output in a biological setting? Transcriptome analysis has proven to be a useful approach...Full Text Available
The aim of the paper is to review the role of interventional radiology in the management of hemodialysis vascular access and complications in renal transplantation. The evaluation of patients with hemodialysis vascular access is complex. It includes the radiology/ultrasound (US) evaluation of the peripheral veins of the upper extremities with venous mapping and the evaluation of the central vein prior to the access placement and radiological detection and treatment of the stenosis and thrombosis in misfunctional dialysis fistulas. Preoperative screening enables the identification of a suitable vessel to create a hemodynamically-sound dialysis fistula. Clinical and radiological detection of the hemodynamically significant stenosis or occlusion demands fistulography and endovascular treatment. Endovascular prophylactic dilatation of stenosis greater than 50% with associated clinical abnormalities such as flow-rate reduction is warranted to prolong access patency. The technical success ...
Background: Some former retrospective studies have suggested that patients with Ewing's sarcoma might have a very high risk for developing secondary sarcomas if treated with radiotherapy. We have evaluated the risk of second malignancies (SM) in patients treated in the German Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and methods: From January 1981 through June 1991, a total number of 674 patients was registered in the two multicentric Ewing's sarcoma trials CESS 81 (1981 through 1985) and CESS 86 (1986 through June 1991). The systemic treatment consisted in both studies of a four-drug-chemotherapy (VACA= vincristine, actinomycin D, cyclophosphamide and adriamycin; or VAIA= vincristine, actinomycin D, ifosfamide and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy was either complete surgery or surgery plus postoperative radiotherapy with 36-46Gy or ...
The accuracy of dose computation within the lungs depends strongly on the performance of the calculation algorithm in regions of electronic disequilibrium that arise near tissue inhomogeneities with large density variations. There is a lack of data evaluating the performance of highly developed analytical dose calculation algorithms compared to Monte Carlo computations in a clinical setting. We compared full Monte Carlo calculations (performed by our Monte Carlo dose engine MCDE) with two different commercial convolution/superposition (CS) implementations (Pinnacle-CS and Helax-TMS's collapsed cone model Helax-CC) and one pencil beam algorithm (Helax-TMS's pencil beam model Helax-PB) for 10 intensity modulated radiation therapy (IMRT) lung cancer patients. Treatment plans were created for two photon beam qualities (6 and 18 MV). For each dose calculation algorithm, patient, and beam quality, the following set of clinically relevant dose-volume values was reported: ...
With the advent of intensity-modulated radiation therapy (IMRT), the inclusion of heterogeneity corrections is further complicated by the conformal delivery of many small beams forming steep dose gradients. Radiation treatment planning has evolved to take into account even small changes in tissue density so that the dose to tumor can be further optimized. However, different treatment planning systems incorporate different heterogeneity correction algorithms, and it is unclear whether any of these algorithms are superior to others in terms of accurately predicting delivered radiation doses relative to measurement in a clinical setting. The purpose of this study was to determine the accuracy of heterogeneity dose calculations from two widely used IMRT treatment planning systems (Pinnacle and Corvus) against measurement. These two systems handle heterogeneity dose corrections by means of a collapsed-cone convolution superposition algorithm and a finite-size ...
The chemist and pharmacologist Fritz Hauschild developed the sympathomimetic agent Pervitin (metamphetamin) in the 1930s. Not only because of the abuse of the stimulant during the Second World War ("pilot's chocolate") it is one of the most controversial substances in drug history. Nearly forgotten are Hauschild's contributions to build up the drug system in the GDR. Although he was a convinced communist, the skilful pharmacologist gave very early warning of the imminent lack of innovation in the GDR pharmaceutical industry. A letter which he addressed to the Minister of Health, Max Sefrin (born 1913), did not lack explicitness. PMID:15997840
Based on the instrumental wavelength dispersive X-ray fluorescence technique of analysis (W D-X R F), the inorganic elements in four samples of commercial medicines drugs were analyzed. The samples were used without any chemical separation of the elements or chemical pre-treatment. Eleven elements could be identified, namely Si, P, S, Cl, K, Ca, Ti, Mn, Fe, Cu and Zn. However, Si, Ti and Mn have not been mentioned in the printed instructions for the use of the medicines drugs by the producers. (author)
The present work gives preliminary results of analysis of drug mixtures (NEPHROSAL tea bag) and its water infusion. In a sample of dried drugs the elements K, Ca, Mn, Fe, Ni, Cu, Zn, Br, Rb, Sr, Pb were identified, whereas in their water infusion only Ca, Mn, Zn and Sr were found. The method applied was radionuclide X-ray fluorescence analysis using a radionuclide source "1"0"9Cd, a Si/Li semiconductor detector and a multichannel analyzer Canberra 8100. (author) 6 refs.; 3 figs.
from a broad range of sources including industrial and consumer products, food additives and drugs that never made it to the market to evaluate the predictive toxicity...
Local anesthetics are frequently administered in dentistry and thus can be expected to be a major source of drug-related complications in the dental office. Additionally, the dentist will more often...Full Text Available
Standardization of herbal formulations is essential in order to assess the quality of drugs, based on the concentration of their active principles. This article reports on standardization of Ajmodadi...Full Text Available
BACKGROUND: An approach to the study of the pharmacokinetics of drugs in the lung is to measure their concentrations in bronchial biopsy specimens. The main criticism of this technique is that bronchial...Full Text Available
Background/Objectives: Cardiotoxic drug poisoning can lead to severe cardiac shock (CS) and death. B-type natriuretic peptide (BNP) is a well-established diagnostic and prognostic marker in heart failure but has never been assessed in patients with cardiotoxic drug poisoning. The aim of the study was to determine whether BNP could be useful for early stratification of patients admitted to intensive care unit. Methods: 30 consecutive patients experiencing shock and cardiotoxic drug exposure were enrolled in a prospective monocentric study and underwent at least two BNP measurements within the first 24 h after admission. Results: While BNP values on admission were poorly informative, subsequent BNP measurements (11 +- 6 h after admission) were significantly increased in patients with CS comp...
Abstract Evaluation of pharmaceutical agents in children is now conducted earlier in the drug development process. An important consideration for this pediatric use is how to assess and support its safety. This article is a collaborative effort of industry toxicologists to review strategies, challenges, and current practice regarding preclinical safety evaluations supporting pediatric drug development with biopharmaceuticals. Biopharmaceuticals include a diverse group of molecular, cell-based or gene therapeutics derived from biological sources or complex biotechnological processes. The principles of preclinical support of pediatric drug development for biopharmaceuticals are similar to those for small molecule pharmaceuticals and in general follow the same regulatory guidances outlined by...
uv irradiation (365 nm) of air-saturated methanol solutions of 20 drugs absorbing in the 300 to 400 nm region gave rise to oxygen uptake, as determined with a polarographic oxygen electrode. The drugs were tested for photosensitizing capability by either a Type I (free radical) or a Type II (single molecular oxygen) mechanism. This testing was done by the inclusion of either acrylamide or 2,5-dimethylfuran in the irradiated drug solution, with observation of the subsequent polymerization or oxidation, respectively. Phenothiazine and thiazide derivatives appear capable of photosensitization by both mechanisms; promethazine, trifluoperazine, and furosemide show relatively high reactivity. Diazepam (weak), hexachlorophene, aminacrine, pyrilamine, tetracycline, demeclocyline, quinine, and anthracene (strong) react only by a Type II mechanism, with a photosensitizing efficiency increasing in the order given. A correlation ...
After fluid resuscitation, vasoactive drug treatment represents the major cornerstone for correcting any major impairment of the circulation. However, debate still rages as to the choice of agent, dose,...Full Text Available
The polyene antibiotic Amphotericin B (AMB) is one of the first therapeutic agents to be marketed commercially as nanosized formulations in which the drug is associated with lipids as liposomes or complexes....Full Text Available
Monitoring describes the prospective supervision, observation, and testing of an ongoing process. The result of monitoring provides reassurance that the goal has been or will be achieved, or suggests...Full Text Available
BACKGROUNDNew diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid,...Full Text Available
Immunomodulatory drugs lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide...Full Text Available
Despite the existence of effective analgesic drugs, many cancer patients live and die with ineffective pain control. The control of cancer pain is largely achievable with the appropriate use of available...Full Text Available
Purpose:This study investigated the penetration of lidocaine around and through a sutured incision following the application of iontophoretic and passive patches...Full Text Available
A case of intraocular coenurosis was clinically diagnosed and treated with praziquantel. The drug destroyed the coenurus, but vision was lost through toxic endophthalmitis and retinal detachment. There...Full Text Available
With the spread of chloroquine resistant Plasmodium falciparum the control of malaria has become increasingly complex. In recent years, particular concern has arisen over how best to prevent malaria...Full Text Available
ObjectiveEpidemiological studies indicate that experimentation with addictive drugs and onset of addictive disorders is primarily concentrated in adolescence and...Full Text Available
Gastrointestinal patches represent a novel multiparticulate drug delivery system able to increase the intestinal absorption of drugs with poor bioavailability. The number of patches to administer is a critical issue since it is related to the surface and drug concentration at the absorption site. The objective of this article is to evaluate the effect of the number of administered patches on the final absorption of leuprolide, a peptide chosen as model drug, assuming complete adhesion of all the devices to the intestinal membrane. The same dose of leuprolide was encapsulated into 2, 4 and 6 patches; the resulting intestinal absorption profiles were measured with the Ussing chamber ex vivo experimental setup and compared between them. The results showed that varying the number of patches, t...
... is reduced: 1) by lack of oxygen, 2) in hypercapnia associated with closed rooms or tents, 3) by use of sleeping drugs, antipyretics, insulin, and 4 ...
Carboxylesterases (CE) are ubiquitous enzymes that hydrolyze numerous ester-containing xenobiotics, including complex molecules, such as the anticancer drugs irinotecan (CPT-11) and capecitabine...Full Text Available
RationaleProcedures for studying the effects of medications on satiation will assist the development of obesity medications.ObjectivesFull Text Available
For a given linac design, the dosimetric characteristics of a photon beam are determined uniquely by the energy and radial distributions of the electron beam striking the x-ray target. However, in the usual commissioning of a beam from measured data, a large number of variables can be independently tuned, making it difficult to derive a unique and self-consistent beam model. For example, the measured dosimetric penumbra in water may be attributed in various proportions to the lateral secondary electron range, the focal spot size and the transmission through the tips of a non-divergent collimator; the head-scatter component in the tails of the transverse profiles may not be easy to resolve from phantom scatter and head leakage; and the head-scatter tails corresponding to a certain extra-focal source model may not agree self-consistently with in-air output factors measured on the central axis. To reduce the number of adjustable variables in beam modelling, we replace ...
To assess the efficacy and resulting complications of tetracycline sclerotherapy in renal, hepatic, ovarian, and perivesical cysts. We retrospectively reviewed 23 cases of benign cysts (16 renal, 4 hepatic, 2 ovarian, and 1 perivesical) in 22 patients in whom the condition was diagnosed or confirmed by either ultrasound, CT, or cytology, and who underwent percutaneous tetracycline sclerotherapy. Using a 21-gauge Chiba needle, the target cyst was punctured under ultrasound guidance. Prior to the injection of 1500 mg of tetracycline diluted in 5 ml of normal saline, almost all the cystic content was aspirated, and at the end of the procedure the tetracycline was left in the cyst. During a period of between 3 and 22 months, 18 of the 23 cases were followed up. In six of the 18 cases followed up, the cysts either decreased in size by 10%, or collapsed completely. In seven cases a collapse of over 50% was noted, and in the remaining five the cyst recurred. In one of ...
Stereotactic radiosurgery (SRS) precisely delivers high-dose radiation to a small target (usually less than 3-4 cm in diameter), in a single session with steep dose-fall, employing various radiation methods. SRS provides good tumor control for small brain metastases from various primary cancers, with minimal untoward effects on surrounding normal brain. This excellent tumor control prevents neurological death and maintains good activity of daily life. Although surgery with whole-brain radiation therapy (WBRT) remains an important option for patients with a solitary brain metastasis, SRS with or without WBRT should be considered in patients with a limited number of small tumors and a good prognosis. Many reports, as well as both retrospective and prospective reviews, have shown WBRT before or after SRS to improve local control and reduce new distant lesion emergence. However, upfront WBRT does not improve survival. There are two major delivery ...
This study examined whether cognitive behavioural therapy (CBT) could prevent the development or worsening of panic-spectrum psychopathology and anxiety symptoms in chronic obstructive pulmonary disease (COPD). 41 patients with COPD, who had undergone pulmonary rehabilitation, were randomised to either a four-session CBT intervention condition (n = 21) or a routine care condition (n = 20). Assessments were at baseline, post-intervention, and at 6-, 12- and 18-month follow-ups. Primary outcomes were the rates of panic attacks, panic disorder and anxiety symptoms. Secondary outcomes were depressive symptoms, catastrophic cognitions about breathing difficulties, disease-specific quality of life and hospital admission rates. There were no significant differences between the groups on outcome measures at baseline. By the 18-month follow-up assessment, 12 (60%) routine care group participants had experienced at least one panic attack in the previous 6 months, with two ...
Humoral immune response to human epidermal growth factor receptor 2 (HER-2/neu or ErbB-2) has been detected in sera of breast cancer patients and shown to be an appropriate prognostic marker (Taylor et al., 2007). However, since Trastuzumab (Herceptin) is a widely used monoclonal antibody as cancer therapy agent for tumors over-expressing HER-2, there is a need for an efficient way to detect host-generated antibodies against HER-2 without the confounding effect of Herceptin. Here we describe a screening method developed to decipher between host antibodies against HER-2 and that of Herceptin. By producing a series of truncation mutants within the epitope of Herceptin, we were able to inhibit this binding. We demonstrated also that by a three amino acid substitution (PPF?SSS) we were able to abrogate Herceptin binding while generating a highly conserved HER-2 extracellular domain (ECD). By producing a stable cell line that expresses this mutated form of the human ...
The Anisotropic Analytical Algorithm (AAA) is a new pencil beam convolution/superposition algorithm proposed by Varian for photon dose calculations. The configuration of AAA depends on linear accelerator design and specifications. The purpose of this study was to investigate the accuracy of AAA for an Elekta SL25 linear accelerator for small fields and intensity modulated radiation therapy (IMRT) treatments in inhomogeneous media. The accuracy of AAA was evaluated in two studies. First, AAA was compared both with Monte Carlo (MC) and the measurements in an inhomogeneous phantom simulating lung equivalent tissues and bone ribs. The algorithm was tested under lateral electronic disequilibrium conditions, using small fields (2x2 cm"2). Good agreement was generally achieved for depth dose and profiles, with deviations generally below 3% in lung inhomogeneities and below 5% at interfaces. However, the effects of attenuation and scattering close to the bone ribs were not ...
The implementation of a three-dimensional conformal radiotherapy facility in the radiotherapy department of the Heinrich Heine University is described. Complex radiotherapy techniques with commercially available networked systems are introduced to improve clinical work. Over 18 month we have gained clinical experience with a PHILIPS Multileaf Collimator (MLC) mounted on a SL 25 linear accelerator. For a limited period the MLC was used as a conventional blocking device. The standard MLC-shapes are controlled with a stand-alone computer system. In addition, a three-dimensional treatment planning system (3-D-TPS / TMS-Radix, Helax AB) based on convolution/superposition algorithms was recently installed. Treatment optimization is achieved using static field arrangements with complete volumetric computerized tomographic patient data for 3-D-TPS. Conformal adaptation of the 95%-isodose to the Planning Target Volume (PTV, ICRU 50) results in MLC-field-shaping concerning ...
A new leaf-sequencing approach has been developed that is designed to reduce the number of required beam segments for step-and-shoot intensity modulated radiation therapy (IMRT). This approach to leaf sequencing is called continuous-intensity-map-optimization (CIMO). Using a simulated annealing algorithm, CIMO seeks to minimize differences between the optimized and sequenced intensity maps. Two distinguishing features of the CIMO algorithm are (1) CIMO does not require that each optimized intensity map be clustered into discrete levels and (2) CIMO is not rule-based but rather simultaneously optimizes both the aperture shapes and weights. To test the CIMO algorithm, ten IMRT patient cases were selected (four head-and-neck, two pancreas, two prostate, one brain, and one pelvis). For each case, the optimized intensity maps were extracted from the Pinnacle"3 treatment planning system. The CIMO algorithm was applied, and the optimized aperture shapes and weights were ...
Experimental excitation functions for deuteron-induced reactions up to 20 MeV on high purity natural hafnium were measured with the activation method using a stacked foil irradiation technique. Metallic hafnium foils with thickness of 10 #mu#m were stacked together with 50 #mu#m thick aluminium and 12 #mu#m thick titanium foils. The aluminium foils served as energy absorber while the titanium foils were used to monitor the energy and intensity of the bombarding deuteron beam. From a detailed remeasurement of the complete excitation function of the "n"a"tTi(d,x)"4"8V monitor reaction it was possible to adopt the proper incident energy and beam intensity by comparing the results with the recommended values. High resolution off-line gamma-ray spectrometry was applied to assess the activity of each foil. From the measured activity independent and/or cumulative elemental or isotopic cross section data for production of Ta, Hf and Lu radioisotopes by (d,x) reactions were determined. No ...
The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin...Full Text Available
BackgroundIt remains unclear if certain antiretroviral medications, particularly abacavir, compromise response to hepatitis C virus (HCV) therapy. Such data can inform...Full Text Available
BackgroundAdolescents have been identified as a high-risk group for poor adherence to and defaulting from combination antiretroviral therapy (cART) care. However, data on outcomes...Full Text Available
A simple device is described which is used to determine treatment distance and beam direction in electron therapy employing one collimation. A technique for the production of irregular field templates and localization films is given.
ObjectivesTo investigate the effect of group cognitive behavioural therapy (CBT) for fatigue self-management, compared with groups receiving fatigue information alone, on fatigue...Full Text Available
BackgroundTo assess the relationship between improved regional and global myocardial function in patients with ischemic cardiomyopathy in response to β-blocker therapy or...Full Text Available
Current adherence assessments typically detect missed doses long after they occur. Real-time, wireless monitoring strategies for antiretroviral therapy may provide novel opportunities to proactively...Full Text Available
BackgroundThe aim of this study was to compare and to validate different dose calculation algorithms for the use in radiation therapy of small lung lesions and to optimize the treatment...Full Text Available
BackgroundThe lack of adequate randomized clinical trials (RCT) has hindered identification of new therapies that are safe and effective for patients with primary focal segmental...Full Text Available
Adaptive radiation therapy (ART) is the incorporation of daily images in the radiotherapy treatment process so that the treatment plan can be evaluated and modified to maximize the amount of radiation...Full Text Available
Photodynamic therapy (PDT) is an established endoscopic technique for ablating Barrett’s esophagus with high-grade dysplasia or early-stage intraepithelial neoplasia. The most common clinically...Full Text Available
Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy...Full Text Available
The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII...Full Text Available
BackgroundHerpes simplex virus (HSV) suppressive therapy reduces genital and plasma HIV-1 RNA over periods up to three months but the longer-term effect is unknown.Full Text Available
Suppressed IL-12 production and maladaptive immune activation, both of which are ameliorated by successful highly active antiretroviral therapy (HAART), are thought to play important roles in the immunopathogenesis...Full Text Available
Purpose: Understanding the kinetics of tumor growth∕shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy....Full Text Available
Purpose:The risks and benefits of continuing bisphosphonate therapy beyond 5 years in patients with primary osteoporosis have not been well established.Methods:We...Full Text Available
Some studies suggest that giving radiation therapy after surgery for hilar cholangiocarcinoma improves the survival rate; however, many of these studies did not specify numbers of subjects or provide an impartial analysis. Thus, we evaluated the effectiveness of radiation therapy as adjuvant treatment after surgery and attempted to establish appropriate adaptation standards. We reviewed the records of 69 patients who underwent surgery for hilar cholangiocarcinoma between June 1980 and April 1998. Thirty-nine patients were treated with surgery followed by radiation therapy and 30 were treated with surgery alone. The clinicopathologic features that might have influenced prognosis were similar in the patients who received radiation therapy and those who did not. Radiation as adjuvant therapy did not have a beneficial effect on overall survival (P=0.554, log-rank test); however, it ...
Multiple disease-specific systematic reviews on the effectiveness of physical therapy intervention for shoulder dysfunction have been inconclusive. To date, there have been two systematic reviews that...Full Text Available
IntroductionThe optimal dialysis dose for the treatment of acute kidney injury (AKI) is controversial. We sought to evaluate the relationship between renal replacement therapy (RRT)...Full Text Available
... and at that point she had already failed physical therapy, which someone else had prescribed, and so ... MRI, we may try a brief course of physical therapy to see if they feel better, but ...
PurposeA dosimetric comparison between multiple static-field intensity-modulated radiation therapy (IMRT), multi-arc intensity-modulated arc therapy (IMAT) and single-arc...Full Text Available
ObjectiveTo report the efficacy and safety of combined photodynamic therapy (PDT) and intravitreal bevacizumab (IVB) injection in the treatment of idiopathic polypoidal choroidal...Full Text Available
Premature circuit clotting is a major problem in daily practice of continuous renal replacement therapy (CRRT), increasing blood loss, workload, and costs. Early clotting is related to bioincompatibility,...Full Text Available
This study was an evaluation of the performance of self-applied, blue light, light-emitting diode therapy in the treatment of mild-to-moderate inflammatory acne on the face, concerning: 1) time to improvement...Full Text Available
BackgroundPostnatal glucocorticoid therapy in premature infants diminishes chronic lung disease, but it also increases the risk of hypertension in adulthood. Since glucocorticoid...Full Text Available
Adjuvant therapy aims to prevent outgrowth of residual disease but can induce serious side effects. Weighing conflicting treatment effects and communicating this information with patients is not elementary....Full Text Available
In many radiotherapy clinics, geometric uncertainties in the delivery of 3D conformal radiation therapy and intensity modulated radiation therapy of the prostate are reduced by aligning the...Full Text Available
The proton therapy gives an irradiation adapted to the shape and the depth of tumors ( eyes, head and neck) with a millimetric, even sub millimetric precision for the ophthalmological tumors. It is equally an excellent tool for the pediatrics tumors. For numerous treatments in France the proton therapy is associated to the photons treatments (x radiation). however, others physical treatments could modulate the medical offer, such thermal therapy or treatments by ultrasonic waves. (N.C.)
The Monte Carlo transport codes LAHET and MCNP were used to calculate energy fluence spectra at three neutron therapy facilities. The results compare very favourably with measured data. Kerma spectra and the ratio of ICRU muscle tissue kerma to A-150 kerma, along the carbon to oxygen kerma ratio, were determined. Absorbed dose rate calculations are in reasonable agreement with measured values. Use of these codes to study modifications to existing therapy beams is briefly discussed. (author).
The anesthetic agents methohexital (Brevital), Innovar, and ketamine (Ketaject) were examined for their effect on seizure duration following electroconvulsive stimulation in a rat model of electroconvulsive therapy (ECT). Compared to unanesthetized control animals, methohexital anesthesia shortened seizure duration by 42%, ketamine anesthesia tended to increase seizure duration, and Innovar anesthesia had no effect on duration of seizures. PMID:7349626
More data about TACE and pTACE seem necessary to better define the global treatment strategy for HCC. Aim of our analysis was to evaluate the role of TACE, either with lipiodol (traditional) or drug-eluting...Full Text Available
Background and ObjectivesClopidogrel resistance or low-responsiveness may be associated with recurrent atherothrombotic events after drug-eluting stent (DES) implantation. We prospectively...Full Text Available
Background. New-generation drug-eluting stents (DES) may solve several problems encountered with first-generation DES, but there is a lack of prospective head-to-head comparisons between...Full Text Available
Synthesis of the azido substituted non-steroidal anti-inflammatory drug 2-(2,6-dichloroanilino)phenylacetic acid and isotope labeling of this compound have been performed and are described. Initial evaluation of the binding ability and photoreactivity indicates that this compound has potential for photoaffinity labeling as well as enzyme selectivity studies. (author).
The heterogeneous solid catalyst, mercaptopropylsilica (MPS), has been prepared by a modified procedure in water and its structure confirmed by solid state carbon-13 CP-MAS NMR spectrum. This catalyst has been efficiently utilized for the synthesis of a wide variety of tri-, tetrasubstituted imidazoles and their bis-analogues at room temperature. The protocol was further explored for the synthesis of the drug trifenagrel.
These three volumes cover liposome technology in pharmacology and medicine. Contributors emphasize methodology used in their own laboratories, and include a brief introduction, coverage of relevant literature, applications and critical evaluations for the methods they describe. Volume II presents procedures for the entrapment of a number of drugs, including genetic material, into selected types of liposomes.
BackgroundAs the promotion of alcohol and tobacco to young people through direct advertising has become increasingly restricted, there has been greater interest in whether images...Full Text Available
The electrochemical oxidation as a method to destroy drug residues like Aspirin {sup trademark}, tetracycline or gentamicin in water was investigated with C-Anode (modified by manganese oxides) and Pt Anode. The mechanism of Aspirin {sup trademark} and tetracycline oxidation and the influence of the biocide effect was observed using GC-MS and three different microbiological tests. In general the biological availability increases with progressive oxidation of the antibiotics. (orig.)
In this study the development of a methodology to detect illicit drugs and plastic explosives is described with the objective of being applied in the realm of public security. For this end, non-destructive assay with neutrons was used and the technique applied was the real time neutron radiography together with computerized tomography. The system is endowed with automatic responses based upon the application of an artificial intelligence technique. In previous tests using real samples, the system proved capable of identifying 97% of the inspected materials.
1 The decreased binding of drugs and dyes to plasma proteins from male and female rats with acute renal failure has been investigated using equilibrium dialysis at 37 degrees C. 2 Acute renal failure...Full Text Available
Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress...Full Text Available
BackgroundNo consensus evidence-based guidelines for the routine laboratory monitoring of children with JIA receiving non-steroidal anti-inflammatory drugs (NSAIDs) exist. The purpose...Full Text Available
The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown....Full Text Available
The patient positioning and repositioning control in radiation therapy all along the treatment can be conducted using a variety of X-ray sources and imaging detector devices. The development of image guided radiation therapy techniques leads to more frequent use of this imaging control. In this article we summarize the current methods for measuring the dose delivered by X-ray imaging devices used in radiation therapy, as well as basic proposals to take account of these imaging doses for prescribing, recording and reporting radiation therapy treatment. (authors)
AbstractBackground: So far, infliximab (IFX) therapy for the treatment of Crohn's disease (CD) has generally been guided by clinical symptoms. Data on treatment response as ascertained by endoscopy in IFX therapy are scarce. The aims of this study were to measure the endoscopic response rate during IFX induction and maintenance therapy in luminal CD, and also evaluate the role of endoscopy in monitoring IFX therapy. Methods: Data obtained from 71 patients with active luminal CD and treated with IFX were analyzed retrospectively. The endoscopy findings were scored according to mucosal activity as: 0 (remission), 1-2 (mild), 3-4 (moderate), and 5-6 (severe). A positive endoscopic response was determined by a decrease in score of at least two points and mucosal healing was assigned a score of...
The two-compartment radioassay for microbial kinetics based on continuous measurement of the {sup 14}CO{sub 2} released by bacterial metabolism of 14C-labeled substrate offers a valuable approach to testing the potency of antimicrobial drugs. By using a previously validated radioassay with gram-positive and gram-negative bacteria, a group of protein synthesis inhibitors was evaluated for their effect on microbial growth kinetics. All tested drugs induced changes in both the slopes and intercepts of the growth curves. An exponential growth model was applied to quantify the drug effect on the processes of bacterial {sup 14}CO{sub 2} liberation and cell generation. The response was measured in terms of a generation rate constant. A linear dependence of the generation rate constant on the dose of spectinomycin was observed with Escherichia coli. Sigmoidal-shaped curves were found in the assays of chloramphenicol and ...
Computational prediction of microRNA targets remains a challenging problem. The existing rule-based, data-driven and expression profiling approaches to target prediction are mostly approached from the...Full Text Available
In order to identify novel high value antibacterial targets it is desirable to delineate whether the inactivation of the target enzyme will lead to bacterial death or stasis. This knowledge is particularly...Full Text Available
Purpose: A retrospective analysis was undertaken to determine the indications for, the efficacy of, and the long-term complications of two courses of total skin electron beam therapy for mycosis fungoides. Methods and Materials: A retrospective analysis of 15 patients with the pathologic diagnosis of mycosis fungoides treated in the Department of Radiation Oncology at Stanford University Medical Center between 1968 and 1990 was performed. All patients received two courses of high-dose electron beam therapy to the skin. The mean dose for the total skin treatment for the first course was 32.6 Gy and 23.4 Gy for the second course of treatment. Results: Following the first course of total skin electron beam therapy, 11 of 15 had a complete response, with a mean duration of 11.6 months. All patients received adjuvant therapies between the first and second courses of high-dose total skin electron beam ...
Little clinical evidence has been provided to show the minimization of radiation resistance of tumors using high linear energy transfer radiation. We therefore investigated the radiobiological and molecular pathological aspects of carbon beam therapy. A total of 27 patients with squamous cell carcinoma (SCC) of the cervix were treated using a carbon beam and 50 control patients with SCC of the cervix using a photon beam. The expression of Ki-67, p53, and p27 proteins before radiotherapy and 5 and 15 days after therapy initiation were investigated using immunohistochemistry. Similar changes were observed in Ki-67 labeling index (LI) and p53 LI during carbon and photon beam therapies. However, for carbon beam therapy, the mean p27 LI significantly decreased from 25.2% before treatment to 18.6% on the 5th day after treatment initiation, followed by a significant increase to 36.1% on the 15th day. In ...
Radiation therapy has had a significant and an expanded role in the management of cancer of the pancreas during the last decade. In particular, for locally advanced disease, radiation therapy has improved the median survival of patients to 1 year. Intraoperative electron beam therapy has been applied to unresectable and resectable pancreatic cancer in an attempt to enhance local control of disease and to improve patient survival. This paper presents a survey of the role of radiation therapy in treatment of cancer of the pancreas, provides information on the radiobiological aspects of this treatment modality and details the physical and dosimetric characteristics of intraoperative radiation therapy with electrons. Presented are the design specifics of an applicator system, central axis beam data, applicator parameters, dose distribution data, shielding, treatment planning and means ...
Radiation therapy has had a significant and an expanded role in the management of cancer of the pancreas during the last decade. In particular, for locally advanced disease, radiation therapy has improved the median survival of patients to 1 year. Intraoperative electron beam therapy has been applied to unresectable and resectable pancreatic cancer in an attempt to enhance local control of disease and to improve patient survival. This paper presents a survey of the role of radiation therapy in treatment of cancer of the pancreas, provides information on the radiobiological aspects of this treatment modality and details the physical and dosimetric characteristics of intraoperative radiation therapy with electrons. Presented are the design specifics of an applicator system, central axis beam data, applicator parameters, dose distribution data, shielding, treatment planning and means ...
Computational fluid dynamics(CFD) code FLUENT was used to simulate the thermal hydraulic processes occurring in conceptual design of the accelerator-driven subcritical reactor(ADSR) liquid lead target. The purpose of the analysis is to investigate the thermal hydraulic characteristics of liquid lead as ADSR target material with various target geometries and injection locations of proton beam. In the calculation analysis, the local temperature of the liquid lead target rises to the boiling temperature very rapidly. When the proton beam is injected from the bottom of the target system, the duration time to reach the boiling temperature is longer and the temperature distribution is flatter than other cases.
Purpose: To report on the nephron-sparing, percutaneous ablation of a large renal cell carcinoma by combined superselective embolization and percutaneous radiofrequency ablation. Materials and Methods: A 5 cm renal cell carcinoma of a 43-year-old drug abusing male with serologically proven HIV, hepatitis B and C infection, who refused surgery, was superselectively embolized using microspheres (size: 500 - 700 {mu}m) and a platinum coil under local anesthesia. Percutaneous radiofrequency ablation using a 7F LeVeen probe (size of expanded probe tip: 40 mm) and a 200 Watt generator was performed one day after transcatheter embolization under general anesthesia. Results: The combined treatment resulted in complete destruction of the tumor without relevant damage of the surrounding healthy renal tissue. The patient was discharged 24 hours after RF ablation. No complications like urinary leaks or fistulas were observed and follow up CT one day and 4 weeks after the ...
The R and D activities of the institute focused on two major projects, ``Molecular and cellular environmental toxicology``, and ``Biophysics of multi-cellular systems``. For assessment of health risks emanating from the uptake of heavy metal compounds, work performed under the first mentioned project studies the formation of allergy-inducing metabolic products from membrane lipids, and the effects of related cellular signaling processes. These studies are accompanied by an approach to quantify and classify the toxicity of environmental organometallic compounds. Another major task is research into the pathogenesis of lung disease induced by dusts, gases, and gas-dust mixtures and the liberation of inflammatory agents by immunological cell reactions (alveolar macrophages). Atomic force microscopy is the tool used to visualize the related dynamic changes in bronchial cells. Studies for detection of the localisation and structure of the Fe-Mo co-factor in nitrogenase by means of the method ...
Methods: Systemic irradiation of neuroaxis is an essential part in the management of medulloblastoma, stPNET and intracranial germ cell tumors. The introduction of quality assurance programs in radiooncology assures a precise radiotherapy of target volumes and is a prerequisite to improve survival. Results: Hyperfractionated radiotherapy has the potential of increasing dose to tumor more safely without increasing the risk for late adverse effects. Pilot studies revealed excellent tumor control in medulloblastoma with acceptable acute toxicity and a long-term survival of up to 96%. In medulloblastoma stereotactic radiation techniques reveal an acceptable toxicity and promising results in tumor control in recurrent disease or as primary treatment. They are now part of future treatment protocols in case of persisting residual tumor. Radiotherapy alone in pure germinoma is continuously yielding high cure rates. In secreting germ cell tumors cisplatin containing ...
Experimental and computational investigations were performed in order to better understand the mechanical response of rigid targets with various geometries to the detonation of shallow buried explosives. The motion of the targets was measured by use of high-speed digital video photography. This work involved flat targets, targets that were downwardly convex, and targets that were downwardly concave with explosive charges located at various positions beneath the targets. It was observed that, in general, angled hulls - whether downwardly concave or convex - tended to reduce the amount of momentum imparted to the center of mass of the targets. Computations were performed by use of an arbitrary Langrangian-Eulerian treatment in a nonlinear finite element code. A model based on quasi-static te...
In an effort to develop octahedral metal complexes as chemotherapeutic and diagnostic agents targeted to DNA, it is critical to optimize the properties of their cellular uptake. Appending d-octaarginine...Full Text Available
The design of the absorber blocks for internal and external dumping of the SPS proton beam is discussed. In addition, the external target stations for slow and fast extracted proton beams are described.
... L. Sutton. 2000. Is the aquatic weed hygrophila, Hygrophila polysperma (Polemoniales: Acanthaceae), a suitable target for classical biological ... ...
Nato SCI-12 on Camouflage Evaluation Workshop on Search and Target Acquisition The Netherlands, June 1999. Image Discrimination Models for Object Detection ...
By W. Wayne Scott. Langley Research Center. SUMMARY. Thin- and thick-target bremsstrahlung spectra are presented for electron energies up to 7.0 MeV. ...
The National Ignition Facility (NIF) is a proposed Department of Energy facility which will contribute to the resolution of important Defense Program and inertial fusion energy issues for energy production in the future. The NIF will consist of a laser system with 192 independent beamlets transported to a target chamber. The target chamber is a multi-purpose structure that provides the interface between the target and the laser optics. The chamber must be capable of achieving moderate vacuum levels in reasonable times; it must remain dimensionally stable within micron tolerances, provide support for the optics, diagnostics, and target positioner; it must minimize the debris from the x-ray and laser light environments; and it must be capable of supporting external neutron shielding. The chamber must also be fabricated from a low neutron activation material. The fusion reaction in the ...
...the School, the research group structure was recently revised and now comprises the following teams: Drug Design and Analysis Pharmaceutics Pharmacy Practice and Policy Pharmacological and Biomedical Science The current structure was designed to take into account the future development of research in the academic area. The ...Discovery, Molecular Modelling, Pharmacology and Molecular Biology) and international recognition (Biological Sciences), which have now been re-organised into the Drug Design and Analysis and Pharmacological and Biomedical Sciences teams. The reorganisation also aimed to improve the research reputation of the other teams. The improvements in ... Email to a friend Print Within this area Drug design and analysis Pharmaceutics Pharmacy practice and policy Pharmacological and biomedical sciences Projects Publications Staff Considering a course? Research Degrees Course Finder Order a Prospectus Subject ...
The cephalosporin class antibacterial agent, cefazolin, was intercalated into layered double hydroxides (LDHs) in order to improve the drug efficiency as well as to achieve the controlled release property. Cefazolin molecules were incorporated into LDH through conventional ion exchange reaction. X-ray diffraction pattern analyses confirmed that cefazolin molecules were intercalated between the interlayer spaces of LDH. Fourier-transform infrared spectra and high performance liquid chromatographs clearly showed that the drug molecules were stabilized in LDH lattice through electrostatic interaction and released without any changes in their chemical integrity. Antibacterial activity of the cefazolin-LDH nanohybrid was also examined by an in vitro test, such as the minimal inhibitory concentr...
Propanolol is a betablocker drug used in the treatment of arterial hypertension related diseases. In order to achieve an optimal performance of this drug it is important to consider the possible interactions of propanolol with plasma proteins. In this work, we have used several experimental techniques to characterise the effect of addition of the betablocker propanolol on the properties of bovine plasma fibrinogen (FB). Differential scanning calorimeter (DSC), circular dichroism (CD), dynamic light scattering (DLS), surface tension techniques and atomic force microscopy (AFM) measurements have been combined to carry out a detailed physicochemical and surface characterization of the mixed system. As a result, DSC measurements show that propranolol can play two opposite roles, either acting ...
A qualitative method, involving supported liquid?liquid extraction (SLE) and ultra high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS?MS), was developed for the rapid tentative identification of various drugs of abuse in urine. In this study, 28 drugs and metabolites were covered by the screening procedure. Before analysis, urine samples were extracted by SLE and good extraction recoveries were obtained for most investigated compounds. The UHPLC strategy was then selected for the rapid separation of amphetamines, cocaine, opiates and related compounds in urine. Using columns packed with sub-2??m particles, analysis time was reduced down to 2?min, while maintaining acceptable performance. Finally, the detection was by tandem MS operating in the single reaction...
Introduction: The QT interval of the electrocardiogram (ECG) reflects the duration of ventricular depolarization and repolarization. A drug-induced prolongation of ventricular repolarization, and thereby QT prolongation, is recognized to be a marker for an enhanced risk for ventricular arrhythmia. The assessment of a drug's effect on the QT interval has therefore become routine within pharmaceutical research and development. However, the heart rate has a major influence on the QT interval; the QT interval shortens as heart rate increases such that one needs to account for such heart rate-dependent changes when evaluating possible drug-induced effects on the QT interval. The relationship between the QT interval and heart rate can be modeled mathematically and using this function a so-called...
The objective of this study was to examine the effect of a nonsteroidal anti-inflammatory drug (NSAID) plaster for knee osteoarthritis among Japanese patients. An open-labeled, randomized, controlled, multiclinic trial was performed involving outpatient clinic groups. Two comparative groups?plaster NSAIDs and oral NSAIDs?were randomly allocated. The drugs used were limited to the current top three in both groups in Japan. Treatments were assessed after four?weeks and compared with the baseline scores. Outcomes were evaluated by two psychometric measures: Japanese knee osteoarthritis measure, and pain with the visual analogue scale. The total number of patients included in the final evaluation was 165 (87 for the plaster group and 78 for the oral group). Between these two groups there were ...
Breath analysis could offer a non-invasive means of intravenous drug monitoring if robust correlations between drug concentrations in breath and blood can be established. In this study, propofol blood and breath concentrations were determined in an animal model under varying physiological conditions. Propofol concentrations in breath were determined by means of two independently calibrated analytical methods: continuous, real-time proton transfer reaction mass spectrometry (PTR-MS) and discontinuous solid-phase micro-extraction coupled with gas chromatography mass spectrometry (SPME-GC-MS). Blood concentrations were determined by means of SPME-GC-MS. Effects of changes in pulmonary blood flow resulting in a decreased cardiac output (CO) and effects of dobutamine administration resulting in...
The aim of this study is to evaluate the specificities of the irradiation of drugs in frozen aqueous solution. The structures of the degradation products were determined to gain insight into the radiolysis mechanisms occurring in frozen aqueous solutions. Metoclopramide hydrochloride and metoprolol tartrate were chosen as models. The frozen solutions were irradiated at dry ice temperature by high energy electrons at various doses. The drug purity (chemical potency) and the radiolysis products were quantified by HPLC-DAD. Characterization of the degradation products was performed by LC-APCI-MS-MS. The structures of the radiolysis products detected in irradiated frozen aqueous solutions were compared to those detected in solid-state and aqueous solutions (previous studies). For both metoclop...
Purpose/Objective: With the advent of computed tomography and magnetic resonance imaging, the three dimensional representation of the patient anatomy has become an invaluable resource for better diagnosis and delineation of the target volume and sensitive structures in radiation therapy. Although the therapeutic linear accelerator industry has made available highly sophisticated equipment, the aggressiveness in dose prescription and delivery has to be complimented by accurate dose computation methods. We have adopted a convolution/superposition algorithm for the calculation of absolute dose that fully accounts for the external shape and internal structure of the patient for photon treatment radiotherapy. In this paper, we will discuss the principles of the convolution algorithm and we will show how the computed dose compares to clinically relevant treatment techniques. Materials and Methods: A computer controlled data acquisition system and a ...
We proposed a solid and a mercury target concepts through the preliminary conceptual design. To feasible these concepts, analysis and experimental works are being carried out. This paper introduces an outline of present status of target R and D such as heat transfer augmentation experiments for the solid target, mercury flow tests with a loop of maximum flow rate of 15L/min, flow pattern measurements for a cold source moderator etc. as well as preliminary conceptual design works. (author)
In the CERN approach to the design of a neutrino factory, the repetition frequency of the proton beam is high enough to consider stationary solid targets as a viable solution for multi-MW beams. The target consists of high density tantalum spheres of 2 mm diameter which can efficiently be cooled by passing a high mass flow He-gas stream through the voids between the Ta-granules. Very small thermal shocks and stresses will arise in this fine grained structure due to the relatively long burst of 3.3 ms from the SPL-proton linac. In a quadruple target system where each target receives only one quarter of the total beam power of 4 MW, conservative temperature levels and adequate lifetimes of the target are estimated in its very high radiation environment. A conceptual design of the integration of the target into the magnetic horn-pion-collector is presented.
For over 50 years, electron beams have been an important modality for providing an accurate dose of radiation to superficial cancers and disease and for limiting the dose to underlying normal tissues and structures. This review looks at many of the important contributions of physics and dosimetry to the development and utilization of electron beam therapy, including electron treatment machines, dose specification and calibration, dose measurement, electron transport calculations, treatment and treatment-planning tools, and clinical utilization, including special procedures. Also, future changes in the practice of electron therapy resulting from challenges to its utilization and from potential future technology are discussed. (review)
Prostate cancer can be successfully treated using dynamic adaptive external beam radiation techniques along with interstitial brachytherapy to deliver curative therapies with low urinary, rectal and erectile function morbidity. Through the use of sophisticated, state-of-the art radiographic imaging for staging and treatment planning, a precise, individual design for treatment is accomplished. Symptom management and patient education are of paramount importance and are integrated throughout the treatment process.
Innovative therapy may appear to coincide with medical experimentation, raising ethical and legal issues, for instance on informed consent and institutional review. Medical treatments may be classified,...Full Text Available
Background and ObjectivePulsed dye laser (PDL) treatment of cutaneous vascular lesions is associated with variable and unpredictable efficacy. Thus, alternative treatment...Full Text Available
Objectives: Acupuncture has served as a major complementary and alternative therapy that supplements conventional medicine and is the subject of growing public interest. This study was conducted to estimate the usage rate of acupuncture as a supplemental treatment in acute ischaemic stroke patients and to identify factors associated with the choice to use this therapy. Methods: Using the registry of stroke patients admitted to an academic medical centre in Korea, the use of acupuncture therapy was recorded and analysed, along with the patients' socio-demographic characteristics, hospital access variables, risk factors for ischaemic stroke and clinical characteristics. The data were analysed using descriptive statistics, chi-square tests and multiple logistic regression analyses. Results: O...
Mycosis fungoides (MF) in deep-seated lymph nodes, spleen or liver appears to be associated with a lack of response of the disease to topical external therapy. Fourteen patients with mycosis fungoides...Full Text Available
Summary: The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased...Full Text Available
Structured abstractObjectiveAlthough most reviews of Pseudomonas aeruginosa therapeutics focus on antibiotics currently in use or...Full Text Available
Penile rehabilitation therapy following radical prostatectomy is a much debated topic. Erectile dysfunction is still a significant contributor to postoperative morbidity following radical prostatectomy, despite meticulous nerve-sparing technique. Secondary smooth muscle changes in the penis have been identified as the underlying causes of penile atrophy, veno-occlusive dysfunction, and fibrosis. Initial observations that intracavernous injection therapies used on a regular basis postoperatively resulted in improvements in the return of spontaneous erectile function led to the development of penile rehabilitation protocols. Chronic dosing of PDE-V inhibitors is now commonly used by urologists after radical prostatectomy. Despite the current enthusiasm of penile rehabilitation therapy, current scientific evidence with clinical trials is still limited. PMID:19255627
BackgroundStump and phantom pains are debilitating sequelae of amputations that are often resistant to treatment. The efficacy of pharmacologic therapies, including...Full Text Available
Modern advances in the concept and the techniques of megavoltage radiation therapy have revolutionized the treatment of medulloblastoma. Five-year survivals of 50 to 70 percent are achieved by craniospinalaxis...Full Text Available
BackgroundLymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus...Full Text Available
SYNOPSISPreterm infants are at risk for both iron deficiency and iron overload. The role of iron in multiple organ functions suggests that iron supplementation is essential for...Full Text Available
Hyperglycemia frequently occurs with acute medical illness, especially among patients with cardiovascular disease, and has been linked to increased morbidity and mortality in critically ill patients....Full Text Available
Development of Portable Normobaric Hypoxia and Pulsed Magnetic Field Firmware System for Enhancement of Radio- and Non-specific Resistance in Workers of Environmentally Hazardous Industries
An elderly man receiving chlorambucil for chronic lymphatic leukaemia developed focal fits. The onset and frequency were dose related. There was no evidence of metabolic disturbance or of meningeal...Full Text Available
The clinical results of electron beam therapy using intraoral cone in 8 cases of primary and recurrence carcinoma of tongue (T1 and smaller T2) were reported. The primary and recurrence cases were 5 and 3, respectively. In the 5 cases, a total dose of 10-30 Gy external radiation therapy were combined prior to electron beam therapy. The total dose of electron beam therapy varied from 40 to 60 Gy. In all cases, tumor showed good response and disappeared clinically. Radiation stomatitis, pain of the tongue with masticatory disturbance due to tenderness were complicated in all cases. These complications gradually disappeared 2 to 6 months after treatment. However, loss of body weight and bone exposure were not recognized in any case. Intraoral-cone electron beam therapy is thought to be available and has less complications comparing interstitial irradiation therapy ...
Purpose: The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. Methods: For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For toxicology studies, immune-competent male mice ...
BackgroundTo investigate the effects of intravenous lignocaine infusions (IV lignocaine) in fibromyalgia.MethodsProspective study...Full Text Available
SynopsisAttention-deficit / hyperactivity disorder (ADHD) is a valid and impairing psychological disorder that persists into adulthood in a majority of cases and is associated...Full Text Available
BackgroundAlthough advances in rehydration therapy have made cholera a treatable disease with low case-fatality in settings with appropriate medical care, cholera continues...Full Text Available
... mammography or on ultrasound but not found on physical examination, we consider them non-palpable or not ... lot of this. We send every patient for physical therapy, no matter what type of reconstruction we ...
Previous research with individuals undergoing surgery or diagnostic procedures provided a conceptual framework for analysis of radiation therapy, a common form of cancer treatment. The present...Full Text Available
Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal...Full Text Available
Adaptive radiation therapy for liver cancer has the potential to reduce normal tissue complications and enable dose escalation, allowing the potential for tumor control in this challenging site....Full Text Available
BackgroundAdequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently...Full Text Available
... 4. Military Working Dogs iMWDs). As used in this Instruction refers to drug detector dogs only. 5. Military Working Doq Executive Agent M(WJDEMA. ...
Background:The manufacturers of oral bisphosphonates (alendronate, risedronate) recommend avoiding use of these drugs in patients with renal impairment. However, many patients who...Full Text Available
The study involved 110 randomly selected dairy farms located in the Ontario, Canada counties of Bruce, Grey, Huron, Oxford, Perth, Waterloo and Wellington. Herds were classified as "intensive" and "extensive"....Full Text Available
Previous studies have shown that salicylates and protein-calorie malnutrition independently compromise maturation and growth of infants. In the present study, pregnant rats were fed normal-and low-protein...Full Text Available
BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available
Recent studies suggest that TJ-41, a herbal drug, possesses chemotherapeutic effects. Accordingly, this study was undertaken to investigate the anticarcinogenic effects of TJ-41 on human breast cancer...Full Text Available
The present study discusses the contribution of the adoption of more rigorous and objective criteria to the selection and analysis of information sources, leading to more scientific rigour when registering phytotherapic drugs. To this end, it is herein proposed the adoption of a previously tested and acknowledged methodology, namely the Systematic Revision, as a standard for phytotherapic drug analyses. In order to show differences brought about by the Systematic Revision during the registration procedures of phytotherapic drugs, the case of the Maytenus ilicifolia (known popularly in Brazil as 'espinheira-santa') is presented. As it is well known, the use of ionizing radiation is expanding, especially in medicine and pharmacy. Therefore, gamma radiation was applied to the microbiological quality control of phytotherapic matrices. Results indicated a positive contribution of Systematic Revision to the ...
Objective:This article examines relationships between reproductive onset and lifetime history of smoking, regular smoking, and nicotine dependence, and cannabis and other illicit...Full Text Available
BackgroundPostoperative delirium is a topic of great importance in the geriatric surgical specialty. Although antipsychotic drugs are the medications most frequently used to treat...Full Text Available
BackgroundRifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month...Full Text Available
SummaryBackgroundThe US FDA has been collecting information on medical devices involved in significant adverse advents since 1984. These reports have...Full Text Available
The safety, pharmacokinetics, and distribution in tissue of an amphotericin B (AmB)-cholesteryl sulfate colloidal dispersion (ABCD) were compared with those of micellar amphotericin B-deoxycholate (m-AmB)....Full Text Available
IntroductionRecent Food and Drug Administration legislation enables the mandating of product performance standards for cigarette smoke and the evaluation of manufacturers’...Full Text Available
Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous...Full Text Available
The effect of adriamycin in combination with radiation on the skin reactions of mouse feet has been examined under a variety of experimental conditions including: (a) hyperthermic treatment of the foot immediately following adriamycin administration, with the former given either just before or just after x irradiation, and (b) fractionated treatments of drug and radiation in a variety of sequences over an 18-day period. In the case of the most severe hyperthermic treatment, no increased radiation reactions were observed in the presence of adriamycin. However, in the case of the less severe hyperthermic treatment a small but significant increase in skin reactions was observed. In the study of fractionated drug and radiation treatments, an enhancement of reaction in those animals receiving combined modality treatment over those receiving radiation alone was seen in those groups where the initiation of drug treatment succeeded ...
The juxtacapsular BNST (jcBNST) is activated in response to basolateral amygdala (BLA) inputs through the stria terminalis and projects back to the anterior BLA and to the central nucleus of...Full Text Available
The in vivo antichlamydial activities of sparfloxacin and reference drugs were examined in a experimental model of pneumonia caused by Chlamydia pneumoniae in leukopenic mice; their in vitro activities...Full Text Available
Treatment of functional bowel disorders of irritable bowel-type (IBS) in children remains a difficult task because of a lack of drugs with low adverse event profile. We here report the results of a...Full Text Available
Indomethacin, a potent nonsteroidal anti-inflammatory drug, has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of indomethacin produces...Full Text Available
Buccal bioadhesive films, releasing topical drugs in the oral cavity at a slow and predetermined rate, provide distinct advantages over traditional dosage forms. The aim of present study was to prepare...Full Text Available
The objective of the present research was to evaluate the physicochemical characteristics of berberine chloride and to assess the complexation of drug with 2-hydroxypropyl-β-cyclodextrin (HPβCD),...Full Text Available
The purpose of the present work was to study the pharmacokinetics and the protein binding (free fraction of the drug) of ceftriaxone (CTX) during pregnancy. Nine pregnant women (ages, 20 to 34 years)...Full Text Available
Current drug treatments for post-menopausal osteoporosis cannot eliminate bone fractures, possibly because the mechanisms responsible for bone loss are not fully understood. Although research within...Full Text Available
Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. While DMSO is generally thought of as being relatively inert, it...Full Text Available
Acetaminophen (APAP) toxicity is the most common drug-induced cause of acute liver failure in the United States. The only available treatment, N-acetylcysteine (NAC), has a limited...Full Text Available
Opioids have been regarded for millennia as among the most effective drugs for the treatment of pain. Their use in the management of acute severe pain and chronic pain related to advanced medical...Full Text Available
The inflammatory process has direct effects on normal and abnormal wound healing. Hypertrophic scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of...Full Text Available
Telbivudine is a novel nucleoside drug recently approved for the treatment of patients with chronic hepatitis B. Its nonclinical safety was evaluated in a comprehensive program of studies, including...Full Text Available
Neonatal bacterial infection in rats alters the responses to a variety of subsequent challenges later in life. Here we explored the effects of neonatal bacterial infection on a subsequent drug...Full Text Available
AimsThe efficacy of topical glucocorticosteroids in rhinitis and asthma is likely to depend on drug retention in the airway mucosa. With fluticasone propionate, retention may be...Full Text Available
Mycophenolate mofetil (MMF) is an immunosuppressive drug that acts as a selective inhibitor of inosine monophosphate dehydrogenase (IMPDH). MMF has recently been shown to inhibit the enzymatic activity...Full Text Available
BackgroundThe zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are...Full Text Available
Integration of solid-state biosensors and lipid bilayer membranes is important for membrane protein research and drug discovery. In these sensors, it is critical that the solid-state sensing...Full Text Available
DNA interstrand cross-links (ICLs) are critical cytotoxic lesions produced by cancer chemotherapeutic agents such as the nitrogen mustards and platinum drugs; however, the exact mechanism of ICL-induced...Full Text Available
The identification of predictive biomarkers is at the core of modern toxicology. So far, a number of approaches have been proposed. These rely on statistical inference of toxicity response from either...Full Text Available
Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug...Full Text Available
A growing number of studies suggest that the development of compulsive drug seeking and taking depends on dorsostriatal mechanisms. We previously observed that ex vivo acute...Full Text Available
Disruption of circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction. Recently, we detected the significant association between prokineticin 2 receptor...Full Text Available
Infection due to multidrug resistance pathogens is difficult to manage due to bacterial virulence factors and because of a relatively limited choice of antimicrobial agents. Thus, it is imperative to...Full Text Available
The nicotinic acetylcholine receptor (AChR) controls signal transmission between cells in the nervous system. Abused drugs such as cocaine inhibit this receptor. Transient kinetic investigations indicate...Full Text Available
The levels of in vitro protein binding of cefonicid and cefuroxime in human adult and neonatal sera were compared. Binding parameters for each drug were determined within the concentration range of...Full Text Available
African trypanosomes exert significant morbidity and mortality in man and livestock. Only a few drugs are available for the treatment of trypanosome infections and therefore, the development of new...Full Text Available
BackgroundMethamphetamine (METH), an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial...Full Text Available
BackgroundControl of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age...Full Text Available
Membranous dysmenorrhea is an unusual clinical entity. It is characterized by the expulsion of huge fragments of endometrium during the menses, favored by hormonal abnormality or drug intake. This report describes a case with clinical, US, and MRI findings before the expulsion. Differential diagnoses are discussed. (orig.)
The full impact of secondary stigma (stigma directed at family) on an HIV-positive individual is unknown. This qualitative research explores perceptions of secondary stigma in the Vietnamese...Full Text Available
Abstract Objective: This study aims to gain an overview of hot topics related to research focused on Chinese herbal drugs by authors inside China and outside of China in the past 10 years. Methods: PubMed/MEDLINE was utilized in order to investigate and select research that was published on ?Chinese herbal drugs?? from 1998 to 2007, by authors located both inside and outside of China (MeSH terms were downloaded and ranked). MeSH terms that frequently appeared were identified and co-word analysis was carried out for two groups: (1) authors located in China, and (2) authors based outside of China, respectively. The hot topics concerning research into Chinese herbal drugs were concluded after cluster analysis and related document analysis. Results: For authors in the China group versus those ...
Several drugs are available for the management of postmenopausal osteoporosis. This may, in daily practice, confuse the clinician. This manuscript offers an evidence-based update of previous treatment...Full Text Available
The D2 antidopaminergic drug Domperidone was evaluated singly and in combination with synthetic adrenocorticoid and an H2 antihistamine for its ability to reduce the acute emetic effects of /sup 60/Co whole-body radiation. Random-source adult male dogs were fasted 12 hours, fed a standard meal, injected 44 minutes later and irradiated 47 minutes after that. Four groups of dogs were radiated after drug injections as follows: saline (Con), domperidone (Dom), cimetidine + thiethylperazine (Cim+Thi), and dexamethasone + domperidone + cimetidine (Dex+Dom+Cim). Drug quantities for dogs represented 10 mg Dom, 10 mg Thi, 20 mg Dex, and 300 mg Cim for an average human (70 ka, 1.8 m2). Subjects were exposed on an up-down schedule to determine the radiation necessary to produce vomiting in 50% (ED50) of each group. Emesis onset times, offset times, and number of episodes were recorded. The ED50 of Dex+Dom+Cim was higher than Con. Dom ...
Ayurvedic drugs have begun to be evaluated in controlled clinical trials. The trials, often placebo controlled, are usually designed to demonstrate superiority. Though the results have been usually...Full Text Available
Dysregulation of glutamate neurotransmission may play a role in cognitive deficits in schizophrenia. Manipulation of glutamate signaling using drugs acting at metabotropic glutamate receptors...Full Text Available
Choice procedures have indicated that the relative reinforcing effectiveness of opioid drugs increases during opioid withdrawal. The demand curve, an absolute measure of reinforcer value, has not been...Full Text Available
1 The influence of the nonsteroidal anti-inflammatory drug naproxen on glucose metabolism and on tolbutamide pharmacokinetics and pharmacodynamics has been studied in ten maturity-onset diabetics. 2...Full Text Available
During antibiotic drug development, media are frequently spiked with either serum/plasma or protein supplements to evaluate the effect of protein binding. Usually, previously reported serum or plasma...Full Text Available
Antivenoms are the currently available agents for treatment of snake venom intoxication in humans. The development of therapeutic strategies employing more generally available drugs could improve treatment of invenomation by reducing hypersensitive reacti...
Drugs used for the inhibition of DNA viruses, such as iododeoxyuridine, adenine arabinoside, or trifluorothymidine, are not biochemically selective in their action and also interfere with normal cellular...Full Text Available
The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T4) to 3,5,3' triiodothyronine (T3) was investigated....Full Text Available
The hepatic uptake rate for certain albumin-bound drugs and metabolites correlates poorly with their equilibrium unbound concentration in the plasma, suggesting that binding equilibrium may not always...Full Text Available
The liver plays a vital role in glucose homeostasis, the synthesis of bile acids and the detoxification of foreign substances. Liver culture systems are widely used to test adverse effects of drugs...Full Text Available
BackgroundWebsites of many rogue sellers of medications are accessible through links in email spam messages or via web search engines. This study examined...Full Text Available
Experiments were performed to investigate the involvement of the cell membrane in the excision DNA repair process in Escherichia coli. Two membrane-binding drugs, procaine and phenethyl alcohol (PEA), inhibited liquid-holding recovery (LBR) in u.v.-irradiated E. coli wild-type and recA strains. In uvrB and polA strains where, after u.v.-irradiation, LHR was absent the two drugs had no effect. Both drugs markedly reduced the removal of u.v.-induced thymine dimers in the DNA of wild-type cells (H/r30). Analysis by alkaline sucrose gradients revealed that PEA inhibited the incision step in excision repair. In contrast, procaine had no effect on incision but apparently inhibited the late steps in excision repair. PEA dissociated DNA from the cell membrane, whereas procaine did not. The results suggest that the two drugs PEA and procaine inhibit LHR and the excision repair process operating on u.v.-induced ...
BackgroundMultidrug resistance (MDR) is a major obstacle in cancer treatment and is often the result of overexpression of the drug efflux protein, P-glycoprotein (P-gp), as a consequence...Full Text Available
Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States....Full Text Available
1 The plasma protein binding of theophylline was determined after addition of [14C]-theophylline (15 micrograms/ml) to plasma from 24 healthy drug-free volunteers and equilibrium dialysis for 2 h at...Full Text Available
Aims:To investigate the relationship between the duration of comatose state, severity of rhabdomyolysis and frequency of peripheral nerve injury (PNI) in patients following...Full Text Available
Tuberculosis (TB) is a major threat to global health, recently exacerbated by the emergence of highly drug-resistant forms of the disease-causing pathogen and synergy with HIV/AIDS. In 2006, the Stop...Full Text Available
Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several...Full Text Available
Mechanism-based inhibition of cytochrome P450 (CYP) 3A4 is characterized by NADPH-, time-, and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYPs to reactive...Full Text Available
We introduce cyclophosphamide-induced alopecia (CYP-IA) in C57BL-6 mice as a clinically relevant model for studying the biology of chemotherapy-induced alopecia and for developing anti-alopecia drugs....Full Text Available
Several investigations suggested abnormalities in circadian rhythms are related to the pathophysiology of psychiatric disorders, including drug addiction. Recently, orphan nuclear receptor rev-erb alpha...Full Text Available
The main objective of Phase I of this SBIR project was to demonstrate the feasibility for successful development of an antimicrobial wound dressing based on a hydrogel sustained release matrix. This goal has been achieved. In vitro studies of drug diffusi...
Currently there is considerable interest among oncologists to find anticancer drugs in Chinese herbal medicine (CHM). In the past, clinical data showed that some herbs possessed anticancer properties,...Full Text Available
Oligopeptidic drugs such as β-lactams and angiotensin-converting enzyme inhibitors share the same carriers in humans and animals, which results in possible pharmacokinetic interactions. To model...Full Text Available
Objectives:The aim of this study was to analyze clinical records of dental patients attending the Dental Department at the University of Jordan Hospital: a teaching hospital in Jordan....Full Text Available
Albumin is a multifunctional transport protein that binds a wide variety of endogenous substances and drugs. Insulins with affinity for albumin were engineered by acylation of the epsilon-amino group...Full Text Available
Two field-adapted colorimetric methods for measuring the antimalarial drug chloroquine in urine are described. Both are modifications of the method of Saker and Solomons for screening urine for phencyclidine...Full Text Available
Albendazole binds to parasite's tubulin inhibiting its glucose absorption. Its common adverse effects are nausea, vomiting, constipation, thirst, dizziness, headache, hair loss and pruritus. Although...Full Text Available
BackgroundThe default mode network (DMN) is a set of brain regions that exhibit synchronized low frequency oscillations at resting-state, and is believed to be relevant to attention...Full Text Available
AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism; its activity is regulated by a plethora of physiological conditions, exercises and many anti-diabetic drugs. Recent...Full Text Available
Plumbagin is found in many herbal plants and inhibits the growth of various bacteria. Escherichia coli strains are relatively resistant to this drug. The mechanism of resistance is...Full Text Available
BackgroundA relevant problem in drug design is the comparison and recognition of protein binding sites. Binding sites recognition is generally based on geometry often combined with...Full Text Available
Background:With the advent of newer antipsychotic drugs, side effects such as sexual dysfunction have been a major contributor toward treatment compliance. There are only...Full Text Available
This study examines the longitudinal relationship between personal and sexual partner incarceration and subsequent HIV risk behaviors among drug-involved men and their primary female sexual...Full Text Available
...1) A privately owned motor vehicle. (2) A privately owned boat. (3) An indigenous animal, military working dog, or guide dog for the blind or visually-impaired accompanying its owner. (4) A narcotic or dangerous drug or...
The use of X-ray scattering techniques in pharmaceutical science is increasing, in part through increased collaborations with the materials science community, and through increased availability of instrumentation, particularly synchrotron sources. The ability to understand not only the biopharmaceutical outcome, but also arguably, more importantly, the structural aspects of drugs and drug delivery systems, is essential to progressing pharmaceutical science; this review serves as an introduction to the major techniques and the wide range of areas in which X-ray scattering may be applied in understanding and controlling structure in pharmaceutical systems.
Glabridin, an active constituent of Glycyrrhiza glabra roots, was found to be active against both yeast and filamentous fungi. Glabridin also showed resistance modifying activity against drug resistant mutants of Candida albicans at a minimum inhibitory concentration of 31.25-250 g/mL. Although the compound was reported earlier to be active against Candida albicans, but this is the first report of its activity against drug resistant mutants. Copyright Copyright 2009 John Wiley & Sons, Ltd.
A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.
OBJECTIVE: To present recent evidence on the use of ovarian hormone therapy (OHT) for osteoporosis and outline safe and effective regimens. OPTIONS: Estrogen alone, estrogen and progestins, progestins...Full Text Available
Recent literature indicates that torsion of the left ventricle (LV) is a promising predictor for response to cardiac resynchronisation therapy (CRT). Among patients with severe heart failure, 45 to 75% of patients show rigid body rotation, where the base and apex rotate in the same direction, instead of normal, opposite rotation. The occurrence of this phenomenon seems to be a good indicator for response to CRT. From this review, it can be concluded that LV torsion might be a welcome addition to current selection criteria.
Purpose: To assess the relationship between large intracranial vessel occlusive vasculopathy (vasculopathy) and radiation therapy, and to clarify the clinical efficacy of magnetic resonance (MR) imaging in the diagnosis and screening of the vasculopathy. Methods and Materials: We retrospectively evaluated the medical records and serial MR images for 32 pediatric patients, in whom radiation therapy had been given to fields including the circle of Willis and major cerebral arteries. All children had periodically undergone follow-up neurologic assessment and MR imaging examinations at Kanagawa Children's Medical Center for more than one year after radiation therapy (range 1.3-14 years). Patients who had not remained free of tumor progression up to the time of final evaluation were excluded. Results: Vasculopathy developed in 6 of 32 patients 2-13 years after radiation therapy. Three of them presented with ...
Electron beam therapy applied to a lymph node metastasis from a squamous cell carcinoma was followed by the development of histologically and immunologically typical bullous pemphigoid, the lesions being initially strictly confined to the irradiation area. This observation suggests that the bullous pemphigoid antigen may be altered or unmasked by electron beam radiotherapy, leading subsequently to the production of autoantibodies. The disease in this case effectively responded to the administration of tetracycline and niacinamide, a therapeutic regimen described recently.
A case is presented in which the diagnosis of acute myelomonocytic leukemia was made 16 months after the start of irradation and chemotherapy for Ewing's sarcoma. The association of these two diseases is rare. The etiologic role of therapy in the development of leukemia is speculative in this case. However, there is need for surveillance for secondary neoplasms of all types so that the benefits of therapy may be properly weighed against the risks.