The in vivo sensitivity of Plasmodium falciparum to chloroquine and sulfadoxine/pyrimethamine was evaluated in children under 5 years of age in two areas of southern Nigeria in 1987. A modification...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
BackgroundArtemisinin-based combination therapy, currently considered the therapy of choice for uncomplicated Plasmodium falciparum malaria in endemic countries,...Full Text Available
SummaryEpigenetic drugs have been shown to enhance gene expression and drugsensitivity in ovarian cancer cell lines and animal models. Based on promising pre-clinical studies,...Full Text Available
Cytoadherence or sequestration is essential for the pathogenesis of the most virulent human malaria species, Plasmodium falciparum (P. falciparum). Similar to leukocyte-endothelium...Full Text Available
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).
Ethnobotanical and chemotaxonomical studies for antiparasitic activity of Colombian Annonaceae were carried out. In vitro antiprotozoal activity of 36 extracts obtained from six different species was determined against promastigotes of three Leishmania species, epimastigotes of Trypanosoma cruzi and both chloroquine sensitive (F32) and resistant (W2) Plasmodium falciparum. Cytotoxic activity was evaluated in U-937 cells. Active extracts were selected according their selectivity index (SI). Extracts from Annona muricata, Rollinia exsucca, Rollinia pittieri and Xylopia aromatica were active against Leishmania spp. and Trypanosoma cruzi showing IC50 values lower than 25mg/ml. Hexane extract from Rollinia pittieri leaves was the most selective against Trypanosoma cruzi and Leishmania spp. (IS=...
The methanol and aqueous extracts of 10 plant species (Acacia nilotica, Azadirachta indica, Carissa edulis, Fagaropsis angolensis, Harrissonia abyssinica, Myrica salicifolia, Neoboutonia macrocalyx, Strychnos heningsii, Withania somnifera and Zanthoxylum usambarensis) used to treat malaria in Meru and Kilifi Districts, Kenya, were tested for brine shrimp lethality and in vitro anti-plasmodial activity against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum (NF54 and ENT30). Of the plants tested, 40% of the methanol extracts were toxic to the brine shrimp (LD5050N. macrocalyx had the highest toxicity to brine shrimp nauplii (LD50 21.04+-1.8mg/ml). Methanol extracts of the rest of the plants exhibited mild or no brine shrimp toxicity (LD50>50mg/ml). The aqueo...
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 ...
BackgroundThe pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra-vascular host cell...Full Text Available
BackgroundPlasmodium falciparum morbid and fatal risks are considerably higher in areas supporting parasite prevalence ≥25%, when compared with low transmission...Full Text Available
BackgroundNaturally acquired immune responses against sexual stages of P. falciparum can reduce the transmission of malaria from humans to mosquitoes. These antigens...Full Text Available
Plasmodium falciparum, the causative agent of human malaria, invades host erythrocytes using several proteins on the surface of the invasive merozoite, which have been proposed...Full Text Available
BackgroundPregnant women are more susceptible to severe Plasmodium falciparum malaria, which can lead to poor maternal and fetal outcomes. Few data exist on the...Full Text Available
A serodiagnostic test has been developed for the detection of Plasmodium falciparum in infected blood. Using parasite antigens and infected red blood cells from in vitro...Full Text Available
The extensive diversity of Plasmodium falciparum antigens is a major obstacle to a broadly effective malaria vaccine but population genetics has rarely been used to guide vaccine design....Full Text Available
There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common...Full Text Available
The malaria parasite Plasmodium falciparum utilizes molecules present on the surface of uninfected red blood cells (RBC) for rosette formation, and a dependency on ABO antigens has...Full Text Available
Naturally acquired immunity to Plasmodium falciparum malaria in malaria holoendemic areas is characterized by the gradual, age-related development of protection against high-density...Full Text Available
Abs are central to malaria immunity, which is only acquired after years of exposure to Plasmodium falciparum (Pf). Despite the enormous worldwide burden of malaria,...Full Text Available
BackgroundXMRV (xenotropic murine leukemia virus-related virus) is the first known example of an exogenous gammaretrovirus that can infect humans. A limited number of reports suggest that XMRV is intrinsically resistant to many of the antiretroviral drugs used to treat HIV-1 infection, but is sensitive to a small subset of these inhibitors. In the present study, we used a novel marker transfer assay to directly compare the antiviral drugsensitivities of XMRV and HIV-1 under identical conditions in the same host cell type.ResultsWe extend the findings of previous studies by showing that, in addition to AZT and tenofovir, XMRV and HIV-1 are equally sensitive to AZddA (3'-azido-2',3'-dideoxyadenosine), AZddG (3'-azido-2',3'-dideoxyguanosine) and adefovir. These results indicate that specific 3'-azido or acyclic nucleoside analog inhibitors of HIV-1 reverse transcriptase (RT) also ...
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 ...
Polyurethane (PU) foam was combined with protein drug-loaded pH-sensitive alginate-bentonite hydrogel for wound dressings. Alginate is a linear copolymer composed of 1?4-linked ?-D-mannuronic acid (M) and its c-5-epimer ?-Lguluronic acid (G). The amount of (M) and (G) and their sequential distribution are varied depending on the alginate source. Soluble sodium alginate can become a hydrogel when cross-linked with divalent cations and has widespread applications in the food, drink, pharmaceutical and bioengineering industries. Recently, it has been also proposed as a biomaterial for drug delivery systems. Bentonites are the natural inorganic polymers consisting of a large proportion of expandable clay minerals with a three-layer structure such as montmorillonite, beidellite, nontronite, etc...
BackgroundPlasmodium falciparum is the most malignant agent of human malaria. It belongs to the taxon Laverania, which includes other ape-infecting Plasmodium...Full Text Available
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There is increasing evidence that adolescence, like early life, is a sensitive period in which ongoing brain development can be influenced by environmental factors. This review describes our use of social instability as a model of mild adolescent social stress, its effects on social interactions and on hypothalamic?pituitary?adrenal function over the course of the procedure and in response to new stressors. The effects of social instability are sex-specific, with qualitative differences between the sexes on HPA function over the course of the stressor procedure, and with greater effects in males on behaviour observed during the social instability and greater effects in females on behavioural responses to drugs of abuse into adulthood, long after the stress exposure. The results from invest...
The metabolism of pentose-phosphate was investigated in Plasmodium falciparum-infected normal and glucose-6-phosphate dehydrogenase (G6PD)-deficient human red blood cells in vitro. 5'-Phosphoribosyl-1-pyrophosphate...Full Text Available
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
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-targeted drugs 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...
Summary Background There is a need for new artemisinin-based combination therapies that are convenient, effective, and safe. We compared the efficacy and safety of pyronaridine-artesunate with that of artemether-lumefantrine for treatment of uncomplicated P falciparum malaria. Methods This phase 3, parallel-group, double-blind, randomised, non-inferiority trial was undertaken in seven sites in Africa and three sites in southeast Asia. In a double-dummy design, patients aged 3-60 years with uncomplicated P falciparum malaria were randomly assigned in a 2:1 ratio to receive pyronaridine-artesunate once a day or artemether-lumefantrine twice a day, orally for 3 days, plus respective placebo. Randomisation was done by computer-generated randomisation sequence in blocks of nine by study centre....
Using the complete genome of Plasmodium falciparum 3D7 which has 14 chromosomes as an example, we have examined the distribution functions for the amount of C or G and A or T consecutively...Full Text Available
BackgroundIndividuals living in malaria endemic areas generally harbour multiple parasite strains. Multiplicity of infection (MOI) can be an indicator of immune status. However,...Full Text Available
BackgroundImproving the understanding of childhood malarial anaemia may help in the design of appropriate management strategies.MethodsA...Full Text Available
The development of rapid and specific diagnostic tests to identify individuals infected with malaria is of paramount importance in efforts to control the severe public health impact of this disease....Full Text Available
BackgroundAn artemisinin-based combination therapy, artesunate (AS) plus sulphadoxine-pyrimethamine (SP), was compared to SP monotherapy to provide evidence of further treatment...Full Text Available
BackgroundIn sub-Saharan Africa, Plasmodium falciparum malaria in pregnancy presents an enormous diagnostic challenge. The epidemiological and clinical relevance...Full Text Available
Merozoite surface proteins have been implicated in the initial attachment to the host red blood cell membrane that begins the process of invasion, an important step in the life cycle of the malaria...Full Text Available
Mechanisms for differential regulation of gene expression may underlie much of the phenotypic variation and adaptability of malaria parasites. Here we describe transcriptional variation among culture-adapted...Full Text Available
BackgroundObtaining single parasite clones is required for many techniques in malaria research. Cloning by limiting dilution using microscopy-based assessment for parasite growth...Full Text Available
Cerebral malaria is the most severe complication of human infection with Plasmodium falciparum. It was shown that Plasmodium berghei ANKA-induced cerebral malaria was...Full Text Available
BackgroundBlood group O has been significantly associated with increased placental malaria infection in primiparae and reduced risk of infection in multiparae in the Gambia, an area...Full Text Available
The identification of genes influencing sensitivity to stimulants and opioids is important for determining their mechanism of action and may provide fundamental insights into the genetics of drug abuse. We used a panel of C57BL/6J (B6; recipient)x A/J (donor) chromosome substitution strains (CSSs) to identify quantitative trait loci (QTL) for both open field activity and sensitivity to the locomotor stimulant response to methamphetamine (MA). Mice were injected with saline (days 1 and 2) and MA (day 3; 2 mg/kg i.p.). We analyzed the total distance traveled in the open field for 30 min following each injection. CSS-8, -11 and -16 showed reduced MA-induced locomotor activity relative to B6, whereas CSS-10 and -12 showed increased MA-induced locomotor activity. Further analysis focused on CSS...
Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats were trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ...
A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP 450) enzyme pathway was inhibited using ketoconazole (KTZ) to see whether a TCBZ-resistant isolate could be made more sensitive to TCBZ action. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP 450 system was inhibited by a 2-h pre-incubation in ketoconazole (40??M), then incubated for a further 22?h in NCTC medium containing either KTZ, KTZ?+?nicotinamide adenine dinucleotide phosphate (NADPH) (1?nM), KTZ?+?NADPH?+?TCBZ (15??g/ml), or KTZ?+?NADPH?+?triclabendazole sulphoxide (TCBZ.SO; 15??g/ml). Changes to fluke ultrastructure following drug treatmen...
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
The aim of the present study is to identify and characterize the antimalrial agents from traitional Sudanese medicinal plants. 49 plants parts representing 26 species from 15 families were extracted and screened for their in vitro antimalrial activity using P. falciparum strain 3D7 which is chloroquine sensitive and Dd2 strain which is chloroquine resistant and pyrimethamine sensitive.The plant species investigated exhibited diverse botanical families. They includes Annonaceae, Aristolochiaceae, Asteraceae, Balantiaceae, Caesalpiniceae, Celasteraceae, Cucurbitaceae, Fabaceae, Graminae, Meliaceae, Myrtaceae, Polygonaceae, Rubiaceae, Rutaceae, and simaroubaceae. The evaluation of these plants for their antimalarial activity and their effect on lymphocyte proliferation was carried out. 57 extracts were tested on the chloroquine sensitive strain (3D7). Where 34 extracts (59%) exhibited significant activity ...
Medical imaging using single gamma-ray-emitting radionuclides typically makes use of parallel hole collimators or pinholes in order to achieve good spatial resolution. However, a tradeoff in sensitivity is inherent in the use of a collimator, and modern preclinical single photon emission computed tomography (SPECT) systems detect a very small fraction of emitted gamma rays, often less than 0.1%. A system for small animal SPECT imaging which uses no collimators could potentially achieve very high sensitivity-several tens of percent-with reasonably sized detectors. This would allow two significant improvements in preclinical studies: images could be obtained more rapidly, allowing higher throughput for screening applications, or for dynamic processes to be observed with very good time resolution; and images could be obtained with less radioactive tracer, making possible the in vivo imaging of low-capacity receptor systems, aiding research into ...
This work reports the development of an automatic methodology based on the use of 1-anilinonaphthalene-8-sulfonate (ANS) as an interfacial fluorescent probe for detecting the hydrophobic environment shift around the probe, caused by the hydrolytic action of PLA2 on the liposomes. The implementation of this reaction in a sequential injection analysis (SIA) system along with the use of the mixing chambers permitted the evaluation of PLA2 activity and assessment of the inhibitory effect of the non-steroidal anti-inflammatory drugs (NSAIDs) on PLA2 activity. Several studies were performed with the aim of establishing the appropriate flow system configuration: the liposome substrate; PLA2 and ANS optimum concentrations and incubation times before and after the enzyme addition. Based on these st...
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 ...
Designer natriuretic peptides (NPs) represent an active area of drug development. In canine and human studies, the designer natriuretic peptide CD-NP demonstrated more desirable therapeutic potential than recombinant B-type NP (BNP), which is known as nesiritide and is approved for treatment of acute decompensated heart failure. However, why CD-NP is more effective than BNP is not known. We previously reported that CD-NP is a poorer activator of human guanylyl cyclase-A (GC-A) and a better activator of human guanylyl cyclase-B than BNP. Here, guanylyl cyclase bioassays were used to compare the susceptibility of CD-NP verses ANP, BNP, CNP and DNP to inactivation by human kidney membranes. The half time (t(1/2)) for CD-NP inactivation was increased by factors of 13, 3 and 4 compared to ANP, BNP and CNP, respectively, when measured in the same assay. Surprisingly, DNP failed to undergo complete inactivation and was the most degradation resistant of the peptides ...
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.).
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
BackgroundThe Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against...Full Text Available
BackgroundThe present study evaluated the SD Bioline Malaria Ag 05FK40 (SDFK40), a three-band RDT detecting Plasmodium falciparum-specific parasite lactate dehydrogenase...Full Text Available
BackgroundSeveral studies have demonstrated the efficacy of artemisinin-combination therapy (ACT) across malaria zones of the world. Fixed dose ACT with shorter courses and fewer...Full Text Available
The detection of rare mutations has many important applications, including risk assessment of drugs and chemicals, measuring environmental exposures to genotoxins, and cancer cell detection. A sensitive genotypic selection method has been developed that combines two different mutant allele selection techniques, MutEx enrichment and allele-specific competitive blocker PCR (ACB-PCR). This method was developed and evaluated for the detection of a CAA --> AAA mutation at codon 61 of the mouse H-ras gene. The MutEx enrichment is based on MutS binding to a mismatched basepair in heteroduplex DNA. The bound MutS protects the mutant allele from degradation during subsequent exonuclease treatment. ACB-PCR preferentially amplifies a mutant allele in a PCR reaction using a primer that has more mismatches to the wild-type allele than the mutant allele. By combining these two approaches, the codon 61 mutation was detected at mutant fractions as low as 1 ...
Pulmonary clearance of an aerosol of "9"9Tc"m DTPA was measured in 21 non-smoking AIDS and pneumocystosis patients. The results were compared with those of pulmonary scintiscanning with gallium. All the patients exhibited increased clearance, evidence of a considerable alteration in alveolar permeability. This increase was also observed in patients with normal chest X-rays and normal blood gases. The average clearance in these patients was 6 #+-# 2% min"-"1 as compared with a normal 1.1 #+-# 0.3% min"-"1. Conversely, only four out of eight patients with normal chest X-rays had abnormal gallium scans. Clearance returned to normal after recovery. Measurement of DTPA clearance appears to be a very sensitive indicator for the detection and follow-up of pneumocystosis. However, it is not very specific since it can be increased by tobacco poisoning, drug abuse and the presence of lymphocytic alveolitis. An examination with normal findings can ...
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 ...
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.
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 bacteria 14 (20.9%), ...
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
... 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
This joint statement was developed by the CMA and the Canadian Pharmaceutical Association, a national association of pharmacists, and includes the goal of drug therapy, strategies for collaboration...Full Text Available
Magnetic drug targeting, 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 simulating the human ...
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. ...
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 drug therapy. 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 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...
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 ...
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 ...
Full text: Many factors including drug efficacy, compliance and antibiotic resistance may influence HP eradication rates. The "1"4C urea breath test is a sensitive method of confirming HP colonisation and eradication. The aim was to study the relationships between the peak "1"4CO_2 counts on the breath test prior to treatment, smoking and HP eradication, and to assess if persistent or recurrent symptoms implied failure of eradication. 117 patients with DU and HP colonisation proved on biopsy or rapid urease test who underwent "1"4C urea breath tests at least one month after eradication treatment was ceased were studied (69 male, 48 female, mean age 41, range 26-87 y). Questionnaire assessment of treatment regimen, smoking history and dyspeptic symptoms was made at the time of the breath test. A sub-group of 43 patients who had pre- and post-treatment breath tests was studied to assess if high peak "1"4CO_2 counts on the pre-treatment breath ...
The electrochemical behavior of the anti-thalassemia and anti-HIV replication drug, deferiprone, was investigated on a carbon nanotube-modified glassy carbon (GC-CNT) electrode in phosphate buffer solution, pH 7.40 (PBS). During oxidation of deferiprone, two irreversible anodic peaks, with E{sub 1}{sup 0}=452 and E{sub 2}{sup 0}=906mV, appeared, using GC-CNT. Cyclic voltammetric study indicated that the oxidation process is irreversible and diffusion controlled. The number of exchanged electrons in the electro-oxidation process was obtained, and the data indicated that deferiprone is oxidized via two two-electron steps. The results revealed that carbon nanotube (CNT) promotes the rate of oxidation by increasing the peak current, so that deferiprone is oxidized at lower potentials, which thermodynamically is more favorable. This result was confirmed by impedance measurements. The diffusion coefficient, electron-transfer coefficient and heterogeneous ...
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 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)
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.
Immunoassays are versatile analytical techniques that had a leading role in various clinical applications, during the last four decades. The studies carried out by Rosalyn Yalow, Solomon Berson and Roger Ekins in the 1960s gave a breakthrough in the development of this novel analytical method. Sensitivity up to femtomolar concentrations, high specificity and universal application to different classes of molecular species made immunoassay a very useful tool in analytical investigation. The expertise acquired by immunochemists in producing antibodies against any antigen and the ability of radiochemists in labeling the antigens with "1"2"5I without affecting the active site are the two main factors responsible for the above development. There are concerns about the safety and health of humans due to the high-level contamination of environment by pesticides, industrial compounds and metals, anabolic steroids in milk and meat products, and presence of mycotoxins in food ...
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
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
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
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
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...
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
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
pT181 is a naturally-occurring 4437 basepair (bp) plasmid isolated from Staphylococcus aureus which encodes inducible resistance to tetracycline (Tc). The DNA sequence data has identified three open reading frames (ORFs). The largest ORF B, has been found to be responsible for the Tc resistance phenotype of pT181. Since most Tc resistance systems appear to be regulated by an effector protein and a repressor protein, several Bal 31 deletion mutants of pT181 were constructed and analyzed in an effort to identify the elements involved in Tc resistance. Two transcomplementing groups of mutants were identified within the tet gene. The mechanism of Tc resistance was studied by assaying the accumulation of (7-/sup 3/H) Tc by Tc sensitive cells, and uninduced and induced pT181-containing cells. A sharp decrease in accumulation of the drug after an initial increase was observed in Tc induced pT181-containing cells. In vivo labeling of Bacillus subtilis ...
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...
...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...
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 targeted drug action and might be a good therapeutic avenue in combating infectious GI disorders.
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...
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...
Probabilistic sensitivities using the score function method are developed for a lifing analysis of an alpha + beta titanium alloy in a round bar under axial fatigue load. Sensitivities with respect to the statistical inputs of the crack initiation size (a...
Two complementary computer programs have been developed for forecasting the demands and evaluating the costs of proposed radiographic facilities. The models are employed here in analyses of the sensitivity...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
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
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 ...
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
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
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
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
Convection-enhanced delivery (CED) has emerged as a promising method of targeted drug-delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate...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
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
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 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
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
BackgroundGene expression profiling and the analysis of protein-protein interaction (PPI) networks may support the identification of disease bio-markers and potential drug targets....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 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
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
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
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
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
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
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
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
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
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...
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
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.
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 affecting local ...
An unsymmetrical squaraine dye which contains an arylamino group was synthesized and used in dye-sensitized solar cells. The molar extinction coefficient of the dye is 77793 M-1 cm-1. Because our synthesized molecule may have no diradical character or the contribution of the diradicaloid component to resonance is quite small, the newly designed squaraine dye has a maximum absorption at 546 nm in the visible region compared with the NIR squaraine sensitizers. Cyclic voltammetry and time dependent density function theory calculation were accomplished to scrutinize the sensitized performance of the dye. Meanwhile, the novel sensitizer has been used to sensitize nanocrystalline TiO2-based solar cell. Under standard global AM 1.5 solar conditions, the squaraine dye-sensitized cell gives a short...
We present numerical calculations for cesium and mercury to estimate the sensitivity of the scattering length to the variation of the fine structure constant alpha. The method used follows ideas Chin and Flambaum [Phys. Rev. Lett. 96, 230801 (2006)], where the sensitivity to the variation of the electron to proton mass ratio, beta, was considered. We demonstrate that for heavy systems, the sensitivity to variation of alpha is of the same order of magnitude as to variation of beta. Near narrow Feshbach resonances the enhancement of the sensitivity may exceed nine orders of magnitude.
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. Patients treated with ...
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 therapy is instituted. ...
Magnolia bark and ginger rhizome is a drug pair in many prescriptions for treatment of mental disorders in traditional Chinese medicine (TCM). However, compatibility and synergism mechanism of two herbs on antidepressant actions have not been reported. The aim of this study was to approach the rationale of the drug pair in TCM. We evaluated antidepressant-like effects of mixture of honokiol and magnolol (HMM), polysaccharides (PMB) from magnolia bark, essential oil (OGR) and polysaccharides (PGR) from ginger rhizome alone, and the possibility of synergistic interactions in their combinations in the mouse forced swimming test (FST) and tail suspension test (TST). Serotonin (5-HT) and noradrenaline (NE) levels in prefrontal cortex, hippocampus and striatum were also examined. 30 mg/kg HMM decreased immobility in the FST and TST in mice after one- and two-week treatment. OGR (19.5 or 39 mg/kg) alone was ineffective. The combination of an ...
DNA polymerase gamma from purified nuclei of EMT-6 cells (mice) seems to be identical to the mitochondrial DNA polymerase from the same source following several criteria. These two enzyme activities are strongly inhibited by ethidium bromide and acriflavin, while proflavin, acridine orange, daunomycin and chloroquine inhibition is less pronounced. In the case of DNA polymerases alpha and beta very little inhibition by ethidium bromide was observed. Intercalation of this dye in a poly dA-dT 12-18 template-primer was studied spectrophotometrically under conditions similar to those in the in vitro DNA polymerase assay. The polymerase assay. The inhibition by this drug of the mitochondrial DNA polymerase gamma activity was shown to be competitive at varying concentrations of TTP while the inhibition was of the non-competitive type at different concentrations of poly dA-dT 12-18. We conclude that the drug, most probably in the intercalated form, is ...
The atomic explosions in Hiroshima and Nagasaki made the name radiation itself become a nightmare. Notwithstanding this, radiation continued to serve the mankind specially in diagnosis of several human diseases and in the treatment of intractable malignancies. With their latest research tools biologists have now shown a significant shift in the earlier paradigm; even the concept that radiation initiates cancer appears to be no longer tenable. On the contrary, selective radiation doses inhibit growth of cancer cells and radiation in combination with many chemotherapeutic drugs, radiosensitizing chemicals and/or hyperthermia, is emerging as a new modality for cancer treatment which offers high therapeutic advantages. In addition, the deleterious effects of radiation can now be strategically counter poised by the use of many drugs and chemicals. This has been possible by the newer insights gained in the mechanism of biological effects of ...
Ex vivo (/sup 3/H)-8-hydroxy-2-(di-n-propylamino)-tetraline ((/sup 3/H)-DPAT) binding to the hippocampus has been utilized to determine the pharmacokinetic parameters of buspirone after i.v. and oral administration of this drug to rats. Intravenous buspirone rapidly penetrated the brain as demonstrated by a maximum inhibition of (/sup 3/H)-DPAT binding at 1 min. Elimination of drug from the brain was biphasic, with a first component half-life of 24.8 min and a second component half-life of 96 min. Oral buspirone at 3 times the i.v. dose produced less than one-third the maximum inhibition of (/sup 3/H)-DPAT binding compared to that observed with i.v. buspirone. The pharmacokinetic parameters of buspirone observed in the present study are in agreement with those reported previously. Thus, the ex vivo binding assay could be utilized to determine the bioavailability of the drug to the brain, and its duration of action. 20 ...
In drug development, Caco-2 cells are often employed to study the influence of membrane transporters on drug permeability. The aim of the current study was to characterize permeability and kinetic parameters of selected organic anionic compounds in Caco-2 cells, and to investigate whether the Caco-2 cell line may be used as an overall model to predict interactions on multiple membrane transporters in the intestine. Taurocholic acid (TCA) and estrone-3-sulfate (E(1) S) were used as model substrates. Possible inhibitors studied were TCA, E(1) S, taurolithocholic acid, fluvastatin, and glipizide. The effects of these compounds on initial uptake, apparent permeability, and intracellular end-point accumulations of the probe substrates were studied. Both interactions on apical and basolateral influx transporters were observed. These interactions were proposed to be mediated mainly by the apical sodium-dependent bile acid transporter and the organic ...
Binary mixtures of dipyrone and pitophenone hydrochloride are assayed by zero-crossing second- and third-derivative spectrophotometry and by ratio-spectra first- and second-derivative spectrophotometry. In the first method, calibration plots are linear at 266.5 and 302.5 nm (dipyrone, second derivative), and 257 and 286 nm (pitophenone second derivative) and 242 and 278.3 nm (dipyrone third derivative), and 228.5 and 300 nm (pitophenone, third-derivative). By the second method, lines of regression are linear at 235 and 262 nm (dipyrone, first derivative), and 229.5 and 288.5 nm (pitophenone, first-derivative), and 249.7 and 268 nm (dipyrone, second derivative), and 280.5 and 300 nm (pitophenone, second-derivative). In all methods calibration curves follow the Beer's law up to 40 microg/ml of each drug. LOD and LOQ values were calculated. The developed derivative spectrophotometric methods were applied to laboratory mixtures and to vials for these ...
To determine clinical predictors and accuracy of {sup 123}I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD). Several clinical features and {sup 123}I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated. DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p<0.05) or PDc (4.5%, p<0.01). Qualitatively {sup 123}I-FP-CIT SPECT images were normal in 29 patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging technique showed high levels of accuracy. DIP and PD are difficult to differentiate based on clinical signs. The precision of clinical diagnosis ...
In this paper, we prepared a novel cationic self-assembled micelle from poly(epsilon-caprolactone)-poly(ethyl glycol)-poly(epsilon-caprolactone) grafted polyethyleneimine (PCEC-g-PEI). The PCEC-g-PEI micelles, formed by self-assembly method, had mean particle size of ca. 82 nm and zeta potential of +22.5 mV at 37 degrees C, and could efficiently transfer pGFP into HEK293 cells in vitro. Meanwhile, as a model hydrophobic chemotherapeutic drug, honokiol was loaded into PCEC-g-PEI micelles by direct dissolution method assisted by ultrasonication. The honokiol loaded cationic PCEC-g-PEI micelles could effectively adsorb DNA onto its surface, while it could release honokiol in an extended period in vitro. This study demonstrated a novel DNA and hydrophobic chemotherapeutic drug co-delivery system. PMID:21121283
This paper contributes to an understanding of pharmacogenomics-in-the-making by foregrounding a regulatory setting in which these technologies must be situated: decision-making about pharmaceutical reimbursement. Health care assessment organizations have been introduced in many countries to systematically address the issue of health care coverage. Using the example of Sweden, the process of deciding reimbursement status is shown to hinge on the creation of stable and clinically feasible categories of patients, diseases and drug responses. Through a series of analogous examples concerning conventional pharmaceuticals, it is argued that current mechanisms for categorizing reimbursable drugs could be upset when pharmacogenomic advances provide a means of making patients more specific objects ...
Ethnopharmacological relevance: Ethnobotanically driven drug-discovery programs include data related to many aspects of the preparation of botanical medicines, from initial plant collection to chemical extraction and fractionation. The Traditional Medicine Collection Tracking System (TM-CTS) was created to organize and store data of this type for an international collaborative project involving the systematic evaluation of commonly used Traditional Chinese Medicinal plants. Materials and methods: The system was developed using domain-driven design techniques, and is implemented using Java, Hibernate, PostgreSQL, Business Intelligence and Reporting Tools (BIRT), and Apache Tomcat. Results: The TM-CTS relational database schema contains over 70 data types, comprising over 500 data fields. Th...
Rationale Receptor occupancy study has been performed to evaluate pharmacokinetic profiles in new antipsychotic drug development. While these findings highlight the value of positron emission tomography (PET) for dose-finding study, what is unclear is if it is necessary to conduct these studies in patients with schizophrenia or whether studies in healthy volunteers are adequate. Objectives To determine if it is necessary to conduct dopamine receptor occupancy studies in patients with schizophrenia or whether studies in healthy volunteers are adequate for dose-finding study, we compared the concentration?occupancy relationship in terms of EC50 between patients and healthy volunteers. Methods Ten healthy volunteers and eight patients with schizophrenia participated in the study. We measured ...
In this work, the antibacterial effect of fluoroquinolones (FQs) upon Escherichia coli (E.coli) was measured with and without application of 40kHz ultrasound (US) stimulation. The research results demonstrated that simultaneous application of 40kHz US apparently enhanced the antibacterial effectiveness of FQs. That is, the synergistic effect was observed and the bacterial viability was reduced when FQs and US were combined. In addition, various influencing factors, such as FQs drug concentration, US irradiation time and solution temperature, on the inhibition of E.coli were also investigated. The antibacterial activity was enhanced apparently with increasing of FQs drug concentration, US irradiation time and solution temperature. Furthermore, we discussed preliminarily the mechanism of US ...
A hypofunctionality of Gi proteins has been found in migraine patients. The fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) is a drug of well-established use in the acute treatment of migraine and tension-type headache. The aim of this study was to investigate if Indoprocaf was able to exert its central antinociceptive action when Gi proteins activity is abolished by pertussis toxin (PTX), compared to its single active ingredients and to sumatriptan. The mice model of abdominal constriction test induced by an i.p. injection of a 0.6% solution of acetic acid was used. The study showed that Indoprocaf (a fixed combination of indomethacin 1?mg/kg, prochlorperazine 1?mg/kg and caffeine 3?mg/kg, s.c.) and sumatriptan (20?mg/kg, s.c.) exert their central antinocicep...
An attempt is made to induce in mud crab (Scylla serrata) epileptiform activities that resemble the generalized epileptic seizures. Cerebral ganglion of crab was exposed in situ, to a convulsant drug pentylenetetrazole (PTZ) 100?mM, for induction of seizures. Also, crabs were pretreated with antiepileptic drug viz sodium valproate (120??mol/l) to inhibit epileptiform activities. The surface electrical discharges of cerebral ganglion were recorded using Unkelscope (MIT, USA) in control as well as experimental animals. The cerebral ganglion of crab showed a pattern of high cerebral electrical discharges after PTZ treatment compared to control. The sodium valproate promoted sedative action in control and prevented PTZ-mediated epileptiform discharges. Glutamate and GABA contents in cerebral g...
A widely used veterinary antibiotic, tetracycline (TC), has been incorporated in Langmuir-Blodgett (LB) films of dipalmitoylphosphatidic acid (DPPA) by means of two different procedures: co-transfer and incubation in solution. The resulting structures were characterized by means of contact angle and ellipsometric measurements. The presence of the antibiotic in the phospholipid film was evidenced by means of UV-Vis electronic absorption and infrared vibrational spectroscopy. The two sets of measurements unambiguously indicated the presence of the drug in the LB layer films obtained with both methods, although incubation led to a smaller content of immobilized tetracycline. In both cases, the drug was found to reside in the hydrophilic portion of the layers due to specific interactions of the dimethylamino group of the molecule with the polar head groups of the phospholipid.
Eight selected sulfonamide drugs were investigated as inhibitors of heat shock protein 90 (Hsp90). The investigation included simulated docking experiments to fit the selected compounds within the binding pocket of Hsp90. The selected molecules were found to readily fit within the ATP-binding pocket of Hsp90 in low-energy poses. The sulfonamides torsemide, sulfathiazole, and sulfadiazine were found to inhibit the ATPase activity of Hsp90 with IC50 values of 1.0, 2.6, and 1.5 mM, respectively. Our results suggest that these well-established sulfonamides can be good leads for subsequent optimization into potent Hsp90 inhibitors.
We have demonstrated that, with simple pH adjustment, volatile drugs such as methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), ketamine, and valproic acid could be analyzed rapidly from raw biofluid samples (e.g. urine and serum) without dilution, or extraction, using atmospheric pressure ionization. The ion source was a variant type of atmospheric pressure chemical ionization (APCI) that used a dielectric barrier discharge (DBD) to generate the metastable helium gas and reagent ions. The sample solution was loaded in a disposable glass pipette, and the volatile compounds were purged by nitrogen gas to be reacted with the metastable helium gas. The electrodes of the DBD were arranged in such a way that the generated glow discharge was confined within the discharge tub...
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 drug targets 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...
After irradiation at 254nm of aqueous solutions of the antipsychotic drug flupentixol, the structures of the photodegradation products were determined by ultra high performance liquid-chromatography linked to mass spectrometry. Fragmentation patterns of the parent ions were established on a hybrid linear ion trap-orbitrap mass spectrometer allowing accurate mass measurements of both parent and daughter ions. This allowed to propose plausible structures for the main photolysis products of flupentixol. A total of nine photoproducts were detected after irradiation of the drug. The main photoproduct is generated following the addition of a hydroxyl group on the double bond adjacent to the thioxanthene ring. Secondary photoproducts were also observed.
Abstract Objectives- Cyclodextrins are useful solubilizing excipients that have gained currency in the formulator's armamentarium based on their ability to temporarily camouflage undesirable physicochemical properties. In this context cyclodextrins can increase oral bioavailability, stabilize compounds to chemical and enzymatic degradation and can affect permeability through biological membranes under certain circumstances. This latter property is examined herein as a function of the published literature as well as work completed in our laboratories. Key findings- Cyclodextrins can increase the uptake of drugs through biological barriers if the limiting barrier component is the unstirred water layer (UWL) that exists between the membrane and bulk water. This means that cyclodextrins are mo...
The goal of this study is to determine whether physicists at the Russian Nuclear Weapons Institute can profitably service the need for computer aided drug design (CADD) programs. The Russian physicists` primary competitive advantage is their ability to write particularly efficient code able to work with limited computing power; a history of working with very large, complex modeling systems; an extensive knowledge of physics and mathematics, and price competitiveness. Their primary competitive disadvantage is their lack of biology, and cultural and geographic issues. The first phase of the study focused on defining the competitive landscape, primarily through interviews with and literature searches on the key providers of CADD software. The second phase focused on users of CADD technology to determine deficiencies in the current product offerings, to understand what product they most desired, and to define the potential demand for such a product.
One-electron oxidation of several derivatives of pyrazolin-5-one, including the drug antipyrine, were studied by pulse radiolysis of aqueous solutions. All the compounds were found to be oxidized by Br2 rapidly but considerably more slowly by weaker oxidants, such as peroxyl radicals. From redox equilibria using p-methoxyphenol and N,N,N',N'-tetramethyl-p-phenylenediamine as reference compounds, the one-electron oxidation potentials of the methyl-substituted 2-pyrazolin-5-ones were found to be in the range of 0.32-0.39 V versus normal hydrogen electrode. The relevance of these findings to the properties of the drug nafazatrom is discussed. Antipyrine was found to have a much higher oxidation potential, estimated as 1.2-1.5 V, which is rationalized on the basis of the phenyl substitution and lack of resonance stabilization of the radical cation.
This paper aims to provide a comprehensive review of the various models or simulations for predicting drug release from bulk-degrading systems. A brief description of bulk degradation processes and factors affecting the degradation rate, and consequently the release kinetics, is presented first. Next, several important classical models, often used as the basis for subsequent model development, are discussed. Both mathematical models and Monte-Carlo based simulations have been developed for controlled release from bulk-degrading systems. The mathematical models can be further subdivided into two categories. First, the diffusion-based models whose transport mechanism is mainly governed by diffusion, but with degradation-dependent diffusion coefficients. These are generally simpler and easier...
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 ...
Abstract Introduction.- Cannabis (marijuana) is the most widely used illicit drug globally. Given the prevalence of nonprescription illicit drug abuse, there is a growing interest in the study of its potential effects on male sexual health. In this review, we discuss the effects of cannabis on male sexual health. Objective.- In this review, we discuss the effects of cannabis on male sexual health. Methods and Main Outcome Measure.- Critical review of scientific literature examining the impact of cannabis use on male sexual health. Results.- Studies examining the effects of cannabis use on male sexual function have been limited in both quality and quantity. Most results of these studies are conflicting and contradictory. While some did outline the beneficial effects of cannabis in enhancing...
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 drug therapy. 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...
The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit (/sup 3/H)diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel.
Phenytoin (PHT), phenobarbital (PHB), lamotrigine (LTG), and topiramate (TPM) are some of the most widely used antiepileptic drugs (AEDs). Monitoring of their concentrations in serum is important for the treatment of epilepsy. A reference measurement procedure (RMP) for certification of PHT, PHB, LTG, and TPM in serum has been developed and critically evaluated. Isotopically labeled compounds of PHT, PHB, LTG, and TPM are used as internal standards for the four AEDs. The four drugs and their respective labeled internal standards are simultaneously extracted from serum using solid-phase extraction prior to reversed-phase liquid chromatography?tandem mass spectrometry (LC-MS/MS). Chromatographic separation was performed using a C18 column. Electrospray ionization (ESI) in the positive ion mo...
The presence of inefficient distribution networks and supply chains of medicines creates problems in that even if African countries can secure steep, sustainable cost-containing procurements, access to needed medicines may still be impaired. The expected health benefits from affordable pricing or subsidies on prices of medicines may not be realized. This article evaluates drug supply chains in African countries and advocates for consolidated private wholesale markets and multiplicity of retail pharmacies. Public supply chains should be shortened and supported by contracting out with private distributors, including wholesalers and retail pharmacies. Additionally, drug regulatory authorities should be allowed to charge registration fees that are proportionate to the costs of technical regula...
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...
BackgroundChanges in ionic concentration have a fundamental effect on numerous physiological processes. For example, IP3-gated thapsigargin sensitive intracellular calcium...Full Text Available
Exercise promotes weight loss and improves insulin sensitivity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Obesity correlates with increased production...Full Text Available
Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary...Full Text Available
G-protein-coupled receptor signalling has been suggested to be voltage dependent in a number of cell types; however, the limits of sensitivity of this potentially important phenomenon are unknown. Using...Full Text Available
Skin sensitization is the most commonly reported occupational illness, causing much suffering to a wide range of people. Identification and labeling of environmental allergens is urgently required to...Full Text Available
PurposeTo assess the relationship between low-grade inflammation, measured as basal high sensitivity (hs)-CRP, and IVF outcome.MethodsWe recruited...Full Text Available
There is increasing consensus that the uterotrophic estrogenicity assay should be coupled with other morphometric or molecular end points that might enhance its sensitivity. We have previously shown...Full Text Available
Increased sensitivity to light-induced melatonin suppression characterizes some, but not all, patients with bipolar illness or seasonal affective disorder. The aim of this study was to test...Full Text Available
The reactive airways dysfunction syndrome (RADS), the reactive upper airways dysfunction syndrome (RUDS), the sick building syndrome (SBS), and the multiple chemical sensitivity syndrome (MCS) are overlapping...Full Text Available
Not all detectable differences between face images correspond to a change in identity. Here we measure both sensitivity to change and the criterion difference that is perceived as a change in identity....Full Text Available
A monensin-sensitive ruminal peptostreptococcus was able to grow rapidly (growth rate of 0.5/h) on an enzymatic hydrolysate of casein, but less than 23% of the amino acid nitrogen was ever utilized....Full Text Available
1. Sensory fibres innervate the adrenal medulla but their function is not known. In this paper we have studied the effect of capsaicin-sensitive sensory fibres on the adrenal catecholamine (CA) response...Full Text Available
This study examined the genetic basis of hypertension and renal disease in Dahl SS/Mcwi (Dahl Salt-Sensitive) rats using a complete chromosome substitution panel of consomic rats in which each of the...Full Text Available
PurposeTo establish normative values for macular light sensitivity and to determine the intrasession fluctuation of perimetric responses using the OPKO/OTI microperimeter.Full Text Available
Heavy ion tests of a switching converter using power MOSFETs have allowed us to identify the main parameters which affect the burnout sensitivity of these components. The differences between static and dynamic conditions are clarified in this paper. (author). 7 refs., 16 figs., 3 tabs.
The sensitivities to cefuroxime and cephradine of potentially pathogenic bacteria isolated in two British general hospitals comprising 900 beds have been assessed. In a three-month period 2537 strains...Full Text Available
Sensitivity and specificity measure inherent validity of a diagnostic test against a gold standard. Researchers develop new diagnostic methods to reduce the cost, risk, invasiveness, and time. Adequate...Full Text Available
Seven mutants of Escherichia coli were isolated that are sensitive to methyl methane sulfonate but not to UV light. They exhibited decreased host cell reactivation capacity for methyl methane sulfonate-treated...Full Text Available
BackgroundFor the detection of allergen-specific IgE in sera, solid-phase IgE-binding assays like the CAP test are commonly used. Although such immunochemical methods are very sensitive,...Full Text Available
Detection and quantification of prion infectivity is a crucial step for various fundamental and applied aspects of prion research. Identification of cell lines highly sensitive to prion infection led...Full Text Available
... comparative analysis is made of the sensitivity of two types of spectrometers: instruments employing coherent spontaneous radiation, and classical ...
... sensitive and classified US Government information, a notable recent example being the unlawful release of classified US documents by WikiLeaks ...
... significant change of spontaneous radiation intensity. It is very sensitive technique allowing the observation of small changes of light absorption. ...
Comparison of the embryolethality of monomeric "2"3"9Pu injected at 9 days of gestation demonstrated that the sensitivity of Charles River CD strain was greater than that of Hilltop Wistar rats. Subsequent comparisons showed that rats derived from the Hilltop Fischer strain were more sensitive than the Wistar and, although not directly compared, more sensitive than the CD.
Spontaneous and ultraviolet-induced changeabilities of wine yeasts from the killer state to sensitive one have been studied. Observed often spontaneous changes of killer and neutral phenotypes under laboratory store conditions as well as high mutation frequency of genetic elements responsible for the killer indication on ultraviolet irradiation testify that often encounterability in nature and in the production of sensitive yeasts is attributed to high frequency of mutation changes of the killer and neutral phenotypes to the sensitive state.
ObjectivesA national survey in 1997 demonstrated that trachoma was endemic in Mali. Interventions to control trachoma including mass drug administration (MDA) with azithromycin were...Full Text Available
Abstract Overall Numbers Small, But Study Finds SSRI Exposure, Autism Link Additional Drug Safety, Efficacy Data Needed for Pediatric Bipolar Disorder SGA Safety and Efficacy in Children and Adolescents Aripiprazole Safety and Tolerability for Irritability in Autism No Lisdexamfetamine Effect on Sleep Disturbances in Children With ADHD Sickle Cell Disease With Comorbid Depression Homeopathy in Psychiatry Manic Symptoms Induced by Marijuana in a Healthy Adolescent New Warnings Safety Labeling Changes
Abstract Clonidine Extended Release Augmentation of Psychostimulants in ADHD ADHD a Risk Factor for Substance Abuse; Cognitive Deficits Not a Predictor Commentary on Kollins et al.; Clonidine XR Augmentation for ADHD Pharmacologic Treatment of Childhood Insomnias Effects of Guanfacine Extended Release on Alertness in ADHD Long Term ADHD Drug Treatment Bipolar Disorder Rates Similar Across Selected Countries Group CBT Alone or Group CBT Plus SSRIs in Childhood Anxiety Resolution of Quetiapine-Induced Oral Dyskinesia From the FDA
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.
Human serum albumin (HSA) has two primary binding sites for drug molecules. These sites selectively bind different dansylated amino acid compounds, which—due to their intrinsic fluorescence—have...Full Text Available
σ-Receptor (σR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of σR ligands in rats trained to self-administer...Full Text Available
... 03/08/2011 Professor named Chair at Epworth Hospital Professor Nilmini Wickramasinghe from the College of Business at RMIT University has been named Epworth Chair, Health Information Management , by Epworth HealthCare. 26/07/2011 Study investigates drug-free relief for tension headaches As Australia marks its first National Pain Week ...
A pro-drug 8 of a synthetic analog 7 is more active in its anti-proliferative activity against human breast cancer MDA-MB-231 cells possessing high Catechol-O-methyltransferase...Full Text Available
Loss of the sense of smell can be easily confirmed in any physician's office by having the patient try to identify various odors. The etiology of anosmia can be extremely varied, including nasopharyngeal disorders such as rhinitis and tumors; neurologic conditions such as head trauma, neoplasms, vascular lesions and infections of the central nervous system; viral infections; familial and congenital disorders; drugs; industrial exposure; endocrine diseases, and several other disorders. The prognosis of anosmia is guarded, and its treatment depends on the etiology.
...Resort and Convention Center, National Harbor, Maryland, USA September 18-20, 2011 XX HELSINKI DRUG RESEARCH CONGRESS Helsinki, Finland October 23-27, 2011 2011 AAPS Annual Meeting and Exposition Washington Convention Center Washington, DC June 26-29 2012 10th International Symposium on Pharmaceutical Sciences Ankara, Turkey Printer-friendly version Home | Elsevier ...
Simultaneous bilateral femoral neck fractures are extremely rare and associated with various conditions. Up to now Most cases had correlations with major trauma, repetitive minor trauma, seizure, parathyroid...Full Text Available
Pharmacological activation of group II metabotropic glutamate (mGlu2 and mGlu3) receptors inhibits reward-seeking behavior and/or rewarding efficacy induced by drugs (cocaine, nicotine) or natural...Full Text Available
BackgroundIntermittent preventive treatment of malaria during pregnancy (IPTp) is a key intervention in the national strategy for malaria control in Tanzania. SP, the current drug...Full Text Available
The aim of this study was to assess the prevalence and correlates of disclosure to network members of being hepatitis C virus (HCV)- or human immunodeficiency virus (HIV)-infected among injecting dyads of infected injection drug users (IDUs) in Budapest, Hungary and Vilnius, Lithuania,. Multivariate generalized estimating equations (GEE) were used to assess associations. Very strong infection disclosure norms exist in Hungary, and HCV disclosure was associated with using drugs and having sex within the dyad. Non-ethnic Russian IDUs in Lithuania were more likely to disclose HCV infection to non-Roma, emotionally close and HCV-infected network members, and to those with whom they shared cookers, filters, drug solutions or rinse water or got used syringes from, and if they had fewer non-IDU or IDU network members. Ethnic Russian Lithuanian IDUs were more likely to disclose HCV if they had higher disclosure attitude and ...
...Correction Discussion Editorial Letter Opinion Review Short Note Technical Note Special Issue all A Systematic Development Method for Rational Drug Design Advances in Molecular Electronic Structure Calculations Algorithms and Molecular Sciences Antimicrobial Agents Application of Density Functional Theory Applications of Density Functional Theory Applications of Molecular Dynamics Atoms in Molecules ...
In order to better understand the molecular mechanisms of human hair growth control and to test hair growth-modulatory drugs, appropriate in vitro models are required. Here, we report the long-term...Full Text Available
BackgroundHepatitis C virus (HCV) infection is the leading cause of chronic hepatitis which progresses to hepatocellular carcinoma (HCC) afflicting > 170 million people worldwide....Full Text Available
A recently developed neutron diagnostic probe system has the potential to satisfy a significant number of van-mobile and fixed- portal requirements for nondestructive verification of sealed munitions and detection of contraband explosives and drugs. The probe is based on a unique associated-particle sealed-tube neutron generator (APSTNG) that interrogates the object of interest with a low-intensity beam of 14-MeV neutrons generated from the deuterium-tritium reaction and that detects the alpha-particle associated with each neutron. Gamma-ray spectra of resulting neutron inelastic scattering and fission reactions identify nuclides associated with all major chemicals in chemical warfare agents, explosives, and drugs, as well as many pollutants and fissile and fertile special nuclear material. Flight times determined from determined from detection times of the gamma-rays and alpha-particles yield a separate tomographic image of each identified ...
BackgroundIn Nigeria ACT use at the community level has not been evaluated and the use of antimalarial drugs (commonly chloroquine (CQ)) at home has been shown to be largely incorrect....Full Text Available
The transcriptional silencing of some cell cycle inhibitors and tumor suppressors, such as p16 and retinoic acid receptor beta(2), by DNA hypermethylation at CpG islands is commonly found in human oral squamous carcinoma cells. We examined the effects of the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza; 0.25 mg/kg body weight), all-trans retinoic acid (RA; given at 100 microg/kg body weight and 1 mg/kg body weight), and the combination of 5-Aza and the low-dose RA on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model. All the drug treatments were done for 15 weeks after a 10-week 4-NQO treatment. Mice in all drug treatment groups showed decreases in the average numbers of neoplastic tongue lesions. The combination of 5-Aza and RA effectively attenuated tongue lesion severity. Although all drug treatments limited the increase in the percentage of ...
The efficiency of electric power generation by dye-sensitized mesoscopic photovoltaic cells has been progressing steadily over the last years reaching now 11% in full sunlight. An important question for practical applications concerns the stability of these devices under prolonged exposure to light or heat. Strikingly stable operation can be obtained by judicious selection of the sensitizer, electrolyte and sealant rendering feasible a service life of at least 20 years under normal outdoor conditions. The sensitizer playing a central role in the light energy conversion process, we analyze the kinetic requirements for it to sustain the required one hundred million turnovers. We also review recent results on the use of self-assembled monolayers of amphiphilic sensitizers and co-adsorbents to enhance the thermal robustness of the device. (author)
The quantum nature of the electromagnetic field imposes a fundamental limit on the sensitivity of optical precision measurements such as spectroscopy, microscopy, and interferometry. The so-called quantum limit is set by the zero-point fluctuations of the electromagnetic field, which constrain the precision with which optical signals can be measured. In the world of precision measurement, laser-interferometric gravitational wave (GW) detectors are the most sensitive position meters ever operated, capable of measuring distance changes on the order of 10^-18 m RMS over kilometer separations caused by GWs from astronomical sources. The sensitivity of currently operational and future GW detectors is limited by quantum optical noise. Here we demonstrate a 44% improvement in displacement sensitivity of a prototype GW detector with suspended quasi-free mirrors at frequencies where the ...
Indoline dye sensitizers were designed and studied theoretically to increase molar extinction coefficients in the visible to near infrared region for solar-cell devices. To gain insight into dye sensitizers' structural, electronic, and optical properties, DFT/TDDFT calculations were performed on a series of dye sensitizers derived from the D149. The good agreement between the experimental and TDDFT calculated absorption spectra of the D149 sensitizer allowed us to provide a detailed assessment of the main spectral features of a series of dye sensitizers. Increase in the conjugation length resulted in a more red-shifted spectral response and less positive oxidation potential than that of the D149. The dye with the dimethylfluorene group showed stronger absorption bands due to a large dipole moment. The calculated dipoles for the dye series correlate well with the observed strong ...
Skin sensitization is the most commonly reported occupational illness, causing much suffering to a wide range of people. Identification and labeling of environmental allergens is urgently required to protect people from skin sensitization. The guinea pig maximization test (GPMT) and murine local lymph node assay (LLNA) are the two most important in vivo models for identification of skin sensitizers. In order to reduce the number of animal tests, quantitative structure-activity relationships (QSARs) are strongly encouraged in the assessment of skin sensitization of chemicals. This paper has investigated the skin sensitization potential of 162 compounds with LLNA results and 92 compounds with GPMT results using a support vector machine. A particle swarm optimization algorithm was implemented for feature selection from a large number of molecular descriptors calculated by Dragon. For ...
The U.S. Department of Energy`s (DOE) Environmental Management Office of Science and Technology (EM-50) authorized studies on alternative systems for treating contact-handled DOE mixed low-level radioactive waste (MLLW). The on-going Integrated Thermal Treatment Systems` (ITTS) and the Integrated Nonthermal Treatment Systems` (INTS) studies satisfy this request. EM-50 further authorized supporting studies including this technology and subsystem cost sensitivity analysis. This analysis identifies areas where technology development could have the greatest impact on total life cycle system costs. These areas are determined by evaluating the sensitivity of system life cycle costs relative to changes in life cycle component or phase costs, subsystem costs, contingency allowance, facility capacity, operating life, and disposal costs. For all treatment systems, the most cost sensitive life cycle phase is the operations and ...
Ten different alloys of zirconium have been tested with regard to the effect of irradiation on their mechanical properties and their sensitivity to environmentally induced failure. Two different environments were used: iodine vapour and liquid cesium with an addition of 2% cadmium. The neutron dose was 10"2"1n/cm"2 (E>1MeV) and the irradiation temperature was about 300 degrees C. All alloy additions increased the irradiation hardening. Especially notable was the large effect of titanium and tin on irradiation hardening. A limited amount of transmission electron microscopy was carried out in order to find an explanation to the effects. The testing in different environments showed that there is no clear correlation between environmental sensitivity and yield stress. For materials of similar yield stress an alloyed material tends to be more sensitive to environmental cracking than a material which only contains oxygen as an ...
In this study, adjoint sensitivity theory is developed for equations of two-dimensional steady-state flow in a confined aquifer. Both the primary flow equation and the adjoint sensitivity equation are solved using the Galerkin finite element method. The developed computer code is used to investigate the regional flow parameters of the Leadville Formation of the Paradox Basin in Utah and the Wolcamp carbonate/sandstone aquifer of the Palo Duro Basin in the Texas Panhandle. Two performance measures are evaluated, local heads and velocity in the vicinity of potential high-level nuclear waste repositories. The results illustrate the sensitivity of calculated local heads to the boundary conditions. Local velocity-related performance measures are more sensitive to hydraulic conductivities. The uncertainty in the performance measure is a function of the parameter sensitivity, parameter ...
The microstructures of magnesium AZ31 are examined following hot compression testing and annealing. The grain size, fraction dynamically recrystallized and, in a couple of cases, the crystallographic texture are reported. It was found that the progress of dynamic recrystallization is strongly sensitive to processing conditions but that the dynamically recrystallized grain size was less sensitive to stress than in other metals. It was also found that, for structures containing between 80 and 95% dynamic recrystallization, abnormal grain growth occurs during annealing. The crystallographic texture produced is also sensitive to the deformation conditions. (orig.)
Yucca Mountain, Nevada is a potential site for a high-level radioactive-waste repository. Uncertainty and sensitivity analyses were performed to estimate critical factors in the performance of the site with respect to a criterion in terms of pre-waste-emplacement ground-water travel time. The degree of failure in the analytical model to meet the criterion is sensitive to the estimate of fracture porosity in the upper welded unit of the problem domain. Fracture porosity is derived from a number of more fundamental measurements including fracture frequency, fracture orientation, and the moisture-retention characteristic inferred for the fracture domain.
The geothermal well-cost model developed by Sandia National Laboratories is being used to analyze the sensitivity of well costs to improvements in geothermal drilling technology. Three interim results from this modeling effort are discussed. The sensitivity of well costs to bit parameters, rig parameters, and material costs; an analysis of the cost reduction potential of an advanced bit; and a consideration of breakeven costs for new cementing technology. All three results illustrate that the well-cost savings arising from any new technology will be highly site-dependent but that in specific wells the advances considered can result in significant cost reductions.
The marine environment is becoming increasingly contaminated by environmental pollutants with the potential to damage DNA, with marine sediments acting as a sink for many of these contaminants. Understanding genotoxic responses in sediment-dwelling marine organisms, such as polychaetes, is therefore of increasing importance. This study is an exploration of species-specific and cell-specific differences in cell sensitivities to DNA-damaging agents in polychaete worms, aimed at increasing fundamental knowledge of their responses to genotoxic damage. The sensitivities of coelomocytes from three polychaetes species of high ecological relevance, i.e. the lugworm Arenicola marina, the harbour ragworm Nereis diversicolor and the king ragworm Nereis virens to genotoxic damage are compared, and dif...
The sensitivity of the primary circuit material was examined at the Mochovce and Dukovany NPPs. No significant sensitivity of the base material or the weld metal to the initiation of corrosion cracking was observed. Thermal aging was found to accelerate significantly the corrosion fatigue kinetics in the material of the heat affected zone. The threshold values of the double amplitudes of the stress intensity factor were below 8 MPa/m"2 for the materials examined, with a cycle asymmetry coefficient of 0.65. The tests revealed no appreciable sensitivity to general corrosion, pitting, or intergranular corrosion. (J.B.). 7 tabs., 26 figs., 11 refs.
BACKGROUNDColorectal cancer (CRC) screening can be administered through tests with varied characteristics and is a preference-sensitive decision.OBJECTIVETo...Full Text Available
Ultraconserved elements (UCEs) are sequences that are identical between reference genomes of distantly related species. As they are under negative selection and enriched near or in specific classes...Full Text Available
... Special Purpse Lead Azide Lot #I3A-4-62 ... Standard X-ray techniques are not sufficiently sensitive ... the National Bureau of Standards, and examined ...
Federal regulators were set to vote on a plan to protect deep water corals and other sensitive fish habitats that will likely include a permanent ban on ...
For some neurotoxic chemicals, neurobehavioral effects are now considered to be among the most sensitive end points yet detected, particularly if exposures occur during critical windows of vulnerability....Full Text Available
Direct radiological measurements of the mineral content of femoral bone were performed in 13 patients on maintenance dialysis. They were found to be sufficiently sensitive to be used for monitoring,...Full Text Available
Aug. 24, 1965. L. V. BALDWIN ETAL. 3202915. PARTICLE BEAM MEASUREMENT APPARATUS USING BEAM KINETIC. ENERGY TO CHANGE TIIE HEAT SENSITIVE RESISTANCE OF ...
All treatments for obesity, including dietary restriction of carbohydrates, have a goal of reducing the storage of fat in adipocytes. The chief enzyme responsible for the mobilization of FFA from adipose...Full Text Available
A growing number of environmental toxicants found in pesticides, herbicides, and industrial solvents are believed to have deleterious effects on development by disrupting hormone-sensitive processes....Full Text Available
A sensitivity study that used the particle tracking code PARMELA was performed on the Advanced Free-Electron Laser (AFEL). The tolerances on the alignment of the beam-line elements and the magnetic-field strengths were examined. Two base-line configurations were determined at the beginning of the study. The electron beam was then matched into the wiggler. The optimized beam-line parameters were varied independently and their sensitivities were judged with the criterion that the free-electron laser (FEL) effective-detuning parameter should not fluctuate more than 10%. The results of this study set the specifications for the alignment, for the sensitivity of the steering magnets, and for the accuracy of the magnetic field in the quadrupoles and dipoles. 5 figs., 3 figs., 3 tabs.
Previous studies indicate that the hatching success of brine shrimp (Artemia franciscana) cysts is surprisingly sensitive to ambient metal concentrations. These studies estimated median effective concentrations (EC50s) of 7, 5, and 28??g l?1 for Cd, Cu, and Zn, suggesting that the hatching end point for A. franciscana is the most sensitive tested to date for Cd and Zn in saline environments and comparable in sensitivity with the most sensitive tested to date for Cu. Furthermore, these data suggest that brine shrimp are at significant risk from Cu and Zn in Great Salt Lake (GSL), UT, where ambient concentrations as high as 10 and 14??g l?1, respectively, have been measured. Given that brine shrimp appear to be successfully reproducing in GSL, we hypothesized that these toxicity values were ...
Perfect single-crystal neutron interferometers are adversely sensitive to environmental disturbances, particularly mechanical vibrations. The sensitivity to vibrations results from the slow velocity of thermal neutrons and the long measurement time that are encountered in a typical experiment. Consequently, to achieve a good interference solutions for reducing vibration other than those normally used in optical experiments must be explored. Here we introduce a geometry for a neutron interferometer that is less sensitive to low-frequency vibrations. This design may be compared with both dynamical decoupling methods and decoherence-free subspaces that are described in quantum information processing. By removing the need for bulky vibration isolation setups, this design will make it easier to adopt neutron interferometry to a wide range of applications and increase its sensitivity.
Purpose To investigate the influence of timolol maleate 0.5% gel-forming solution and brinzolamide 1% ophthalmic suspension on contrast sensitivity, ocular higher-order aberration (HOA), and corneal surface light scattering. Design Prospective, comparative study. Participants Forty normal volunteers were enrolled in this study. Methods We evaluated contrast sensitivity, ocular HOA, and corneal light scattering before and 2, 5, 10, and 15 minutes after instillation of antiglaucoma eyedrops. Contrast sensitivity function was assessed with the CSV-1000RN chart (Vector Vision Co., Greenville, OH). Higher-order aberration was measured for a 4-mm pupil using the Hartmann-Shack aberrometer (KR-9000PW; Topcon, Tokyo, Japan). Corneal surface light scattering was quantitatively evaluated by using th...
BackgroundAutofluorescence bronchoscopy is more sensitive than conventional bronchoscopy for detecting early airway mucosal lesions. Decreased specificity can lead...Full Text Available
Chemoreceptors are crucial components in the bacterial sensory systems that mediate chemotaxis. Chemotactic responses exhibit exquisite sensitivity, extensive dynamic range and precise adaptation....Full Text Available
SummaryThis paper examines the sensitivity and uncertainty of evaporation estimates from Nasser Lake, south of Egypt using data collected at the floating station Raft, 2km upstream of the Aswan High Dam, and 12 evaporation models. Based on their approach the evaporation models were ranked in five classes, respectively the Bowen ratio energy budget (BREB) approach, three energy-aerodynamic based methods, a mass transfer method, two temperature and five solar radiation-temperature approaches. State dependent parameter models were used to estimate the sensitivity indices of the different evaporation estimation methods at daily and monthly frequencies. A drastic reduction in the cost of the sensitivity analysis was obtained when coupled with efficient sampling methods, producing quasi-Monte Ca...
Most commercially based activated charcoal radon collectors were designed for use in indoor environments. However, at present, they are often used for research in radon surveys in unique environments, such as in the bathrooms, underground areas, mines, caves and tunnels. In these environments, the relative humidity would be around 100%, and a change in the sensitivity of cpm(Bq m{sup -3}){sup -1}(radon) would occur. For this study, the reduction in the sensitivity of activated charcoal radon collector due to environmental humidity was investigated, and the data correction was discussed. Here, ST-100 (Pico-Rad) was selected as an example of a familiar activated charcoal radon collector. According to our performance test, the humidity of 90% (20 deg. C) resulted in a 15% reduction of the sensitivity for 24 h collection. The ST-100 user should discuss the necessity of data correction by comparing the change of ...
mulation, with flow quantities stored at the grid vertices. OVERFLOW ..... attack: a separation bubble near the trailing edge of the ..... AGARD CP-429, Jul. 1988. ...
We present a technique for identifying the amino acids responsible for a loss of immunoreactivity in response to treating an antigen with a chemical modifier. This is of particular interest...Full Text Available
This work showed the formation of phospholipid vesicle coating on inorganic sericite surface with characterization by combining electron microscopy of FE-SEM, TEM, AFM, and qualitatively evaluated the coated phospholipid vesicle by XPS as a function of etching time. The possibility of phospholipid vesicle mobility on the surface was restrained by the chelation effect of magnesium cation. The stabilization properties of phospholipid vesicles on sericite surface were demonstrated by the various concentration of magnesium cation. The presence of magnesium was found to have a much more pronounced influence on the lipid deposition process. The Mg cation plays an important role for attaching the phospholipids with optimum concentration of 7 mM. Totally, the phospholipid vesicles coating on inorganic powder could be useful for bio-related fields such as cosmetics and drug delivery system as the key functional compounds. We hope this basic result lead to a general and ...
This study sought to quantitate lidocaine's interaction with alpha-1-acid glycoprotein (AAG), human serum albumin (HSA), and AAG in the presence of HSA, and to determine the extent of displacement of lidocaine from its binding site(s) by selected cardiovascular drugs (dipyridamole, disopyramide and quinidine). Since the limited experimental work reported in this area has involved the use of a single lidocaine concentration, this study involved the evaluation of a range of lidocaine concentrations. Lidocaine interaction with plasma proteins (AAG and HSA) was studied at 37/sup 0/C using an isothermal equilibrium dialysis system and /sup 14/C-lidocaine HCl. A dialysis membrane (M.W. cutoff 12,000 to 14,000) separated the two chambers of each dialysis cell. The extent of /sup 14/C-lidocaine dialysis was studied with respect to both drug and protein concentrations. Aliquots of each chamber of each of the cells were subjected to liquid ...
Two-component mixtures of dorzolamide hydrochloride and timolol maleate were assayed by first derivative and ratio derivative spectrophotometric methods. The first method, derivative spectrophotometry, by the zero-crossing measurements, was used due to the drugs closely overlapping absorption spectra. Linear calibration graphs of first derivative values at 250.3 nm for dorzolamide hydrochloride and 315.8 nm for timolol maleate. The second method, is based on ratio first derivative spectrophotometry, the amplitudes in the first derivative of the ratio spectra at 242.9 and at 223.5 nm were selected to determine dorzolamide and timolol maleate in the binary mixture. Calibration graphs were established for 8.0-30.0 microg ml(-1) for dorzolamide hydrochloride and 3.0-24.6 microg ml(-1) for timolol maleate in binary mixture. Good linearity, precision and selectivity were found, and the proposed methods were applied successfully to the pharmaceutical dosage from ...
The purpose was to study the toxicity of drugs known to generate free radicals on isolated pancreatic islets. The accumulattion of "8"6Rb"+ by mouse pancreatic islets was measured in vitro. Exposing the islets to 6-hydroxydopamine, minhydrin, or phenazine methosulphate + NADH inhibited the Rb"+ uptake, whereas paraquat or acetylphenylhydrazine had no effect. This effect of 6-hydroxydopamine was prevented by either of the hydroxyl radical scavengers, sodium benzoate and mannitol, but not by the non-scavenger,urea; ninhydrin was partially protected against by mannitol but not by benzoate. Protection against 6-hydroxydopamine was also afforded by D-glucose but not by L-glucose or 3-O-methyl-D-glucose; none of the sugars protected against ninhydrin. In damaging islet beta-cells and in being protected against by D-glucose, 6-hydroxydopamine closely resembles the diabetogenic drug, alloxan. It is suggested that protection against alloxan may involve ...
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 ...
Summary.? It is widely believed that hepatocellular cancer (HCC), especially HBV associated HCC, is highly resistant to chemotherapy. To investigate the molecular influence of HBx protein on multidrug resistance (MDR) in HCC and the potential role of the NF-?B pathway in this process. We established HBx-expressing cells by liposome-mediated transfection of the HBx into the HepG2 cell line. We found that HBx expression in HCC cells induces drug resistance against multiple drugs, a significantly lower apoptosis ratio in HepG2-HBx and HepG2.2.15 cells, compared with HepG2 and HepG2-3.1 cells (P?HCC cells were downregulated by IMD-0354 treatment, which is the NF-?B pathway inhibitor. Taken together, these results suggest that HBx protein might be one of the causes for the occurrence of MDR in HCC, and the NF-?B pathway might be involved in this change. PMID:21914061
2,3-Dimercaptosuccinic acid (DMSA) is a new orally active heavy metal chelator for the treatment of childhood Pb intoxication on an outpatient basis. The influence of DMSA, as well as other chelating agents, on gastrointestinal 203Pb absorption and whole-body "2"0"3Pb retention was examined. Groups of Sprague-Dawley rats (230-260 g) were gavaged with a solution containing approximately 25 mg/kg Pb [as Pb(NO_3)2] plus 15 microCi "2"0"3Pb. Some groups were then immediately given 0.11 mmol/kg of either DMSA, CaNa2EDTA, D-penicillamine, or BAL by oral gavage, while other groups received the same drugs by ip injection. Control groups received solutions of the drug vehicles po or ip. Whole-body Pb retention and gastrointestinal Pb absorption (whole body retention + urinary Pb excretion) were significantly decreased in rats that received DMSA po. This finding implies that the use of DMSA to treat childhood lead intoxication on an outpatient basis is ...
Summaries are presented for those research contracts which expired between December 31, 1960 and December 31, 1981. Topics covered include: factors controlling distribution of fission products in biosphere, non-destructive methods of evaluating the U/sup 235/ and Pu content of irradiated fuel elements, studies of contamination in local marine resources, tracer studies of anemia, non-destructive analysis of irradiated fuel elements using a flux integrating monitor, mechanism of proteolysis of I/sup 131/-labeled fibrinogen, radiosensitivity of spermatogonia of Drosophila melel elements by gamma scanning, uptake and loss of radioactive material by marine bacteria, factors which influence the movement of radioactive strontium from soils to plants, biological concentration of fission products in mollusks from water, decay scheme of Tl/sup 210/, calcium balance in metabolic bone disease, development of radioactive drugs with special reference ...
The purpose of this study was to prepare recombinant human epidermal growth factor (rhEGF) collagen sponges for topical applications and investigate the effects of different types of crosslinked collagen sponges as platforms for the controlled release of rhEGF. The microstructure and the drug release rates of collagen sponges were modified through treatment with different types (glutaraldehyde (GTA), genipin and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)), different concentrations of crosslinking agents and various preparation conditions. A controlled release profile was observed for the crosslinked collagen sponges as compared to the non-crosslinked ones. The results indicated that the GTA crosslinked sponges have the most potent controlling effect. As the amount of GTA increased, a greater rigidity of the collagen sponge structure combined with a lower hydrophilicity was observed, leading to a decreased drug release rate and an ...
The purpose of this study was to determine if a cannabinoid CB1 receptor antagonist would selectively decrease consumption of highly palatable food in non-human primates. The CB1 receptor antagonist SR141716 (rimonabant; 0.12?1.0?mg/kg, i.m.) and the stimulant anorectic drug d-amphetamine (0.12?1.0?mg/kg, i.m.) were administered to non-food deprived baboons for the purpose of measuring the effect of each drug on consumption of the normal diet, and a large single meal of a high-carbohydrate candy. Four male and four female baboons had access to food 24?h each day, but they had to complete a two phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, where responding on another lever led to...
Abstract Common single nucleotide polymorphisms (SNPs) in SMAD7 (18q21) have been linked to colorectal cancer (CRC) risk in genome-wide association studies, but little is known about their effects on survival. SMAD7 regulates gastrointestinal inflammation by inhibiting transforming growth factor- (TGFB), which can act as both a tumor suppressor and a promoter of metastasis. Regular use of cyclooxygenase-2 (COX2) inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), reduces the risk of developing CRC. Because COX2 overexpression reduces the growth suppressing effects of TGFB, we hypothesized that survival may depend on both SMAD7 genotype and prediagnostic NSAID use. Postmenopausal women, ages 50-74, diagnosed with incident invasive CRC from 1997 to 2002 were identified using t...
Benz(a)pyrene (BP) levels in extracts and solvent cake obtained by alcoholic and aqueous extraction of specimens of 20 different medicinal plants were measured to explore into the possibility of its passage from these plants to drugs. Seventy percent alcoholic extracts were found to contain 40-60% of BP passed from raw material, while aqueous extracts--2-3% (in some cases 10-14%). Maximal concentrations of BP in alcoholic extracts were 0.6-0.7 micrograms/1 and 0.03-0.04 micrograms/1--in aqueous ones. A significant correlation between BP level in extracts and its content in plants was established. BP pathways in the course of solasodine manufacturing from nightshade (Solanum lacinatum) were studied. As little as 1% of BP passed to extract after primary extraction in 2%--sulfuric acid. Solasodine contained about 3 micrograms/kg of BP.
We studied the interactions of tetracycline (TC) antibiotic molecules with phospholipid monolayers with the two-fold aim of elucidating the mechanism of action and providing a first step for the realization of bio-mimetic sensors for such drugs by means of the Langmuir-Blodgett technique. We examined spreading monolayers of three phospholipids in the presence of tetracycline in the subphase by means of surface pressure-area and surface potential-area isotherms as a function of bulk pH. We selected phospholipids with hydrophobic chains of the same length but polar head groups differing either in dimensions and protonation equilibria, i.e. dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylethanolamine (DPPE) and dipalmitoylphosphatidic acid (DPPA). The interaction of tetracycline with the three phospholipids was found to be highly dependent on the electric charge of the antibiotic and on the ionization state of the lipid. Significant interactions are ...
Multiwall carbon nanotubes (MWCNTs) were functionalized with a photosensitizer, rosebengal (RB), and folicacid (FA), an anti-cancer drug simultaneously and individually, which was characterized with various analytical instruments like Fourier Transform Iinfrared (FTIR) spectroscopy, UV?Vis spectroscopy, Thermogravimetric analysis (TGA), Photoluminescence (PL) spectroscopy, X-ray photoelectron spectroscopy (XPS), and Transmission electron microscopy (TEM). FTIR spectra confirmed the chemical modification of MWCNT. The chemical functionalization of MWCNT with RB was further supported by UV?Vis and PL spectra.
The synthesis and biophysical characterization of four prodrug ether phospholipid conjugates are described. The lipids are prepared from the anticancer drug chlorambucil and have C16 and C18 ether chains with phosphatidylcholine or phosphatidylglycerol headgroups. All four prodrugs have the ability to form unilamellar liposomes (86-125 nm) and are hydrolyzed by phospholipase A2, resulting in chlorambucil release. Liposomal formulations of prodrug lipids displayed cytotoxicity toward HT-29, MT-3, and ES-2 cancer cell lines in the presence of phospholipase A2, with IC50 values in the 8-36 ?M range.
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 drug therapies. Corticotropin-releasing factor (CRF) concentrations are elevated in a subset of anxiety disorders, which suggests the potential utility of CRF receptor antagoni...
A number of herbal drugs are used in the Unani (Greco-Arab) System of Medicine for cardiovascular diseases. The herbs were analyzed by flame AAS and ICP-AES to determine if their therapeutic actions can be associated with the elements present in them. Cadmium, cobalt, chromium, copper, iron, potassium, magnesium, manganese, sodium, nickel, phosphorus, lead and zinc were some of the elements which play various roles in cardiovascular affections. An effort was made to correlate the role of these elements in cardiac diseases. (Auth.). 2 tabs., 32 refs.
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.
In an effort to improve the extrapolation of laboratory data to man and estimate risk of human reproductive toxicity associated with environmental exposure, the pharmacokinetic parameters of the testicular compartment are being studied. Of particular interest is the variety of enzyme systems capable of activating and detoxicating environmental chemicals and drugs. This report compares the metabolism of benzo(a)pyrene by the isolated perfused testis and testicular homogenates in vitro. The cell free in vitro system metabolized benzo(a)pyrene at a much greater rate than the perfused testis and produced a different spectrum of metabolites. Reliable laboratory prediction of biotransformation by the whole organ or intact animal is an essential aspect of reproductive toxicology.
This review begins with an historical account of biomaterials applications followed by a concise description of the phenomena taking place between the living tissues and non-living materials containing them. After describing the requirements for biodegradability and the mechanisms involved, a thorough literature survey of such polymers is presented. In the end a very short review of the work done in this area by the authors in recent years is given, including: the synthesis of a wide variety of biodegradable di-and tri-block copolymers, preparation of microparticles; stealth-and immuno-liposomes; dendrosomes and polymersomes; and some of their applications in drug and gene delivery.
Scientists at JPL have developed chemical and biological techniques using microspheres filled with drugs, electron-opaque metals, or radioactive, fluorescent, magnetic or electrically charged materials to label specific groups of cells. Synthetic polymeric microspheres are coupled with specific antibodies to form reagents called immunomicrospheres, which can seek out and attach themselves to any specific group of cells. These cell-labeling techniques, therefore, open new avenues not only to the basic study of cells but also to the diagnosis and treatment of many diseases, including cancer.
The aim of this study was to investigate the photodegradation of the antiemetic drug metoclopramide. Metoclopramide aqueous solutions were photoirradiated at 254nm under argon atmosphere. Irradiated metoclopramide solutions were analyzed by high performance liquid chromatography-ion trap mass spectrometry in order to characterize photolysis products. Rapid decrease in metoclopramide purity, following first-order kinetic, was observed following irradiation. The structures of 18 photolysis products were tentatively identified based on their mass spectra and fragmentation. The main degradation mechanism was scission of the chlorine which could be followed by polymerization of the resulting products since dimeric and trimeric products were observed.
The results of treatment of 134 cases of morphologically-verified localized Ewing's sarcoma were evaluated. A comparative analysis showed relapse-free survival to be significantly lower for radiation treatment (23 %) than for its combination with various cytostatic drugs. Two-year relapse-free survival rate was as high as 43 % in cases receiving sarcolysin or cyclophosphamide as adjuvants. This was matched by 47 % for adjuvant ardiamycin or carminomycin and 56 % for adriamycin plus cyclophosphamide and vincristine. Evaluation of long-term results of adjuvant chemotherapy showed sex, age and site involvement to be of certain prognostic value.
A commonly reported consequence of post-treatment nausea or vomiting is the development of anticipatory nausea and vomiting (ANV). In most published work, nausea is reported to occur before chemotherapy drugs are administered by approximately 20% of patients at any one chemotherapy cycle and by 25?30% of patients by their fourth chemotherapy cycle. Most studies in adult patients strongly support the view that the development of ANV involves elements of classical conditioning. The best method to avoid development of ANV is to adequately prevent both vomiting and nausea from the first exposure to chemotherapy. If anticipatory side effects develop, behavioral treatment techniques, such as systematic desensitization, have been shown effective. Benzodiazepines used in combination with behaviora...
The emergence of bacterial antibiotic resistance is a growing problem, yet the variables that influence the rate of emergence of resistance are not well understood. In a microfluidic device designed to mimic naturally occurring bacterial niches, resistance of Escherichia coli to the antibiotic ciprofloxacin developed within 10 hours. Resistance emerged with as few as 100 bacteria in the initial inoculation. Whole-genome sequencing of the resistant organisms revealed that four functional single-nucleotide polymorphisms attained fixation. Knowledge about the rapid emergence of antibiotic resistance in the heterogeneous conditions within the mammalian body may be helpful in understanding the emergence of drug resistance during cancer chemotherapy. PMID:21940899
We examined whether perceived susceptibility to and severity of two injection-related health conditions (i.e., non-fatal overdose and bacterial infections), and perceived benefits of, barriers to, self-efficacy to, social acceptance of, and recent use of two harm-reduction behaviors (i.e., injecting test shots and pre-injection skin cleaning), predicted injecting drug users' near-term intentions to engage in these two strategies. Recent past use of these two behaviors consistently and positively predicted near-term intentions in each of four drug-use situations (i.e., in withdrawal, not in withdrawal, alone, and with others). Perceived susceptibility to non-fatal overdose predicted intentions to do test shots, but only when participants imagined not being in withdrawal or injecting when alone. Perceived self-efficacy to clean one's skin predicted intentions to engage in this behavior, but only when participants imagined injecting while not in ...
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 pump genes most ...
Lipase catalyzed esterification of therapeutic drugs to functional self-assembled monolayers (SAMs) on 316L stainless steel (SS) after assembly has been demonstrated. SAMs of 16-mercaptohexadecanoic acid (-COOH SAM) and 11-mercapto-1-undecanol (-OH SAM) were formed on 316L SS, and lipase catalysis was used to attach therapeutic drugs, perphenazine and ibuprofen, respectively, on these SAMs. The reaction was carried out in toluene at 60 degrees C for 5 h using Novozyme-435 as the biocatalyst. The FTIR spectra after surface modification of -OH SAMs showed the presence of the C=O stretching bands at 1745 cm(-1), which was absent in the FTIR spectra of -OH SAMs. Similarly, the FTIR spectra after the reaction of the -COOH SAM with perphenazine showed two peaks in the carbonyl region, a peak at 1764 cm(-1), which is the representative peak for the C=O stretching for esters. The second peak at 1681 cm(-1) is assigned to the C=O stretching of the ...
We wanted to assess the usefulness of four-dimensional (4D) ultrasonography (US), i.e., real-time three-dimensional US, as an adjunct for performing various US-guided interventional procedures in superficial lesion. Thirty-three patients were referred for US-guided interventional procedures for superficial lesions, including core biopsy in 19, fine- needle aspriation in eight, therapeutic drug injection in four and needle puncture in two. The procedures were performed under 4D US guidance. We reviewed the pathologic/cytologic results of the core biopsies or needle aspirations, and also the outcomes of drug injection or needle puncture. For all the patients who underwent 4D US-guided core biopsy, the specimens were adequate for making the pathological diagnosis, and specimens were successfully obtained for those patients who underwent 4D US-guided aspiration. The patients treated with 4D US-guided therapeutic drug injection ...
The /sup 13/C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to /sup 13/C-AP breath tests, neonates have a very low capacity to eliminate /sup 13/CO/sub 2/, which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs /sup 13/C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerably stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, /sup 13/C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme induction demonstrated by /sup 13/C-AP breath ...
Two neutron emesis experiments were conducted at the Armed Forces Radiobiology Research Institute (AFRRI). In both experiments (described as Phase I and Phase II) the radiation dose required to cause emesis in 50% of subjects (ED50) was determined for both neutron reactor and gamma reactor source radiation. Emesis onset, offset and duration times post-exposure are reported. Neutrons were maximized from the reactor by passing the beam through a 15.25 cm (6 in.) thick lead wall to filter out gamma photons. Gamma rays were maximized by thermalizing neutrons in 30.5 cm (12 in.) of water, then absorbing the thermal neutrons in a gadolinium-cadmium shield. In Phase I, 28 dogs were exposed to radiation: 12 were exposed to gamma photons at the rate of 0.69 Gy/min and 16 were exposed to neutrons at 1.2 Gy/min. In Phase II, 58 dogs in 3 groups were exposed to radiation: 19 were exposed in the gamma group at 0.75 Gy/min, 20 were exposed in the undrugged neutron group at 1.62 Gy/min, and 19 were ...
Performance assessments for the Area 5 Radioactive Waste Management Site on the Nevada Test Site have used three different mathematical models to estimate Rn-222 flux density. This study describes the performance, uncertainty, and sensitivity of the three models which include the U.S. Nuclear Regulatory Commission Regulatory Guide 3.64 analytical method and two numerical methods. The uncertainty of each model was determined by Monte Carlo simulation using Latin hypercube sampling. The global sensitivity was investigated using Morris one-at-time screening method, sample-based correlation and regression methods, the variance-based extended Fourier amplitude sensitivity test, and Sobol's sensitivity indices. The models were found to produce similar estimates of the mean and median flux density, but to have different uncertainties and sensitivities. When the Rn-222 effective ...
To analyse the thermal noise of the pendulum mode of a suspended mirror, we interferometrically detect the differential movement of two mirrors suspended as multiple-stage pendulums. We present the set-up of this experiment and the current sensitivity, and also the different steps that we took in the past to increase the sensitivity, which include an auto alignment of the laser beam into the resonator eigenmode, changes of the seismic isolation system to more damping stages and higher moments of inertia and an intensive noise hunting.
Using a sensitive optical wavelength modulation technique the surface-plasmon excited on a gold grating surface immersed in sulfuric acid is studied at the same time as cyclic voltammetry is undertaken. Because of the optical sensitivity of the modulation technique significant optical effects are observed at potentials well below those at which any gross oxidation effects occur.
A network of second-generation low-temperature gravitational radiation detectors is nearing completion. These detectors, sensitive to mechanical strains of order 10"-"1"8, are possible because of a variety of technical innovations that have been made in cryogenics, low-noise superconducting instrumentation, and vibration isolation techniques. Another five orders of magnitude improvement in energy sensitivity of resonant-mass detectors is possible before the linear amplifier quantum limit is encountered. 33 references, 3 figures, 1 table.
1. We studied the effects of flash photolysis on the novel enantiomeric cardiac inotropes EMD 57033 (a calcium sensitizer) and EMD 57439 (a phosphodiesterase III inhibitor) in rat isolated ventricular...Full Text Available
The NREL Sensitized Solar Cell (SSC) Core Program supports the Solar America Initiative by: (1) targeting new devices and processes for commercialization by 2015 that are less expensive, more efficient, highly reliable, and environmentally benign; (2) collaborating with DOE OS/BES to conduct basic research targeting breakthroughs in key areas, such as ultra-high efficiency and/or ultra-low cost materials and devices.
The neutron detector is cased in a metal envelop and has one detector with a very sensitive fission chamber and a second detector with a fission chamber less sensitive that the first one and a boron coated ionisation chamber for reducing gamma radiation detection.
This comprehensive, critical review summarizes the use of nanoparticles in enhanced and amplified chemiluminescence detection, illustrated by different reaction strategies, electrogenerated chemiluminescence sensors, immunoassay or hybridization labels and electrogenerated chemiluminescence immunoassay or hybridization sensors. We discuss the analytical applications on the basis of validity, range and sensitivity, and draw some useful conclusions about the most sensitive approach in each type of application.
The results show that the SQUID device eddy current testing system is a suitable tool for NDE. Due to the high low-frequency sensitivity of the SQUID sensor, the SQUID device eddy current testing system permits lower examination frequencies than the conventional eddy current probe system. The SQUID system enhances fault detection in even deeper materials layers. (orig./MM).
The sensitivity and specificity of the MGIT TBc identification (TBc ID) test for Mycobacterium tuberculosis complex (MTC) detection in positive Bactec MGIT cultures were 95.2% and 99.2%, respectively. When MTC-positive results obtained from two additional molecular methods were included, the sensitivity of the MGIT TBc ID test was 85.4%, while that of culture was 95.7%. PMID:21450949
The effect of the polyamine oxidase (PAO)-polyamine system on some helminths was examined in vitro. Both Schistosoma mansoni schistosomula and Dirofilaria immitis microfilariae were highly sensitive...Full Text Available
Design of a beam position monitor (BPM) which is sensitive to low velo charged particle beams is considered. Quantitative estimates are made for the corrections to the conventional approximations to solutions of the Laplace Equation in two-dimensions when a BPM is used to measure to position of low velocity (low-[beta]) beams. (AIP)
Temperature-sensitive mutants defective in 60S ribosomal subunit protein L16 of Saccharomyces cerevisiae were isolated through hydroxylamine mutagenesis of the RPL16B gene and plasmid shuffling. Two...Full Text Available
In clinical situations where a diagnostic real-time PCR assay is not sensitive enough, leading to low or falsely negative results, or where detection earlier in a disease progression would benefit the...Full Text Available
The in situ assembly states of the glucose transport carrier protein in the plasma membrane and in the intracellular (microsomal) storage pool of rat adipocytes were assessed by studying radiation-induced inactivation of the D-glucose-sensitive cytochalasin B binding activities. High energy radiation inactivated the glucose-sensitive cytochalasin B binding of each of these membrane preparations by reducing the total number of the binding sites without affecting the dissociation constant. The reduction in total number of binding sites was analyzed as a function of radiation dose based on target theory, from which a radiation-sensitive mass (target size) was calculated. When the plasma membranes of insulin-treated adipocytes were used, a target size of approximately 58,000 daltons was obtained. For adipocyte microsomal membranes, we obtained target sizes of approximately 112,000 and 109,000 daltons prior to and after insulin ...
In the fields of medical imaging, geophysical well logging, and industrial radiography, it is often of interest to characterize the spatially distributed sensitivities of neutron and gamma-ray measurement devices to the physical properties of the materials being examined. For instance, one may wish to know how the count rate in a detector varies in response to small changes in the local density of the irradiated object as a function of position. Experimental determination of such sensitivity functions is often impractical. Consequently, we have developed a general three-dimensional Monte Carlo numerical technique that allows us to directly compute the differential sensitivity of an arbitrary integral response parameter, such as a time- or energy-discriminated count rate, with respect to the spatial distribution of macroscopic cross sections and sources in the irradiated medium. Sensitivities to object ...
The adjoint of an ocean general circulation model is used as a tool for investigating the causes of changes in ENSO SST indices. We identify adjoint Kelvin and Rossby waves in the sensitivities to sea level and wind stress at earlier times, which can be traced back for more than a year through western and weak eastern boundary reflections. Depending on the thermocline depth the first and second baroclinic modes are excited. The sensitivities to the heat flux and SST are local and decay in about a month. The sensitivities to the fluxes are converted into the influence of SST using the adjoint of a statistical atmosphere model. Focusing on SST perturbations in the index region itself, we recover, up to a scale factor, the delayed oscillator concept.
The properties of individual radioactive particles present in a sample, such as a swipe, are more interesting than bulk properties of the sample. The present work focuses on instrumentation that provides position-sensitive spectral information non-destructively from the sample. The experimental part of the work was realized using a device called PANDA (Particles And Non-Destructive Analysis). The detector setup used in the study contains a broad-energy HPGe gamma-ray detector and a position-sensitive alpha detector. Both detectors are connected to a time-stamping event-mode data acquisition system. The method is shown to locate particles with sub-millimetre accuracy and distinguish the interesting particles from non-interesting ones. (author)
An imaging position sensitive detector for charged particles, neutrons, X-and gamma rays has been developed. The novel feature of this scintillation imaging radiation detector is its ability to detect individual nuclear particle scintillations with a h igh degree of spatial resolution. The key elements of this detector system are a high gain, low noise image intensifier tube, a CCD camera and commercially available image processing hardware and software. This detector system is highly effective for applications such as low fluence and real time neutron radiography, mapping of radioactive contamination in nuclear reactor fuel rods, X-ray diffraction imaging, high speed autoradiography and in general position sensitive detection of nuclear radiation. Results of some of the exploratory experiments carried out using this detector system are presented in this paper. (orig.).
In this paper, four different types of pulsed eddy current (PEC) probe are designed and their performance of detecting wall thickness reduction is compared. By using the backward difference method in time and the finite element method in space, PEC signals from various thickness and materials are numerically calculated and three features of the signal are selected. Since PEC signals and features are obtained by various types and sizes of probe, the comparison is made through the normalized features which reflect the sensitivity of the feature to thickness reduction. The normalized features indicate that the shielded reflection probe provides the best sensitivity to wall thickness reduction for all three signal features. Results show that the best sensitivity to thickness reduction is achieved by the peak value, but also suggest that the time to peak can be a good candidate because of its linear relationship with the ...
The authors have shown that toxicity of paraquat for Escherichia coli is increased over 1-fold in strains defective in the biosynthesis of spermidine compared to isogenic strains containing spermidine. The increased sensitivity of these spermidine-deficient mutants to paraquat is eliminated by growth in medium containing spermidine or by endogenous supplementation of spermidine by the use of a speE"+D"+ plasmid. No paraquat toxicity is seen in the absence of oxygen, even in amine-deficient strains, indicating that superoxide is the agent responsible for the increased toxicity. However, the specific mechanisms responsible for the increased paraquat toxicity in the spermidine-deficient mutants remain to be determined. The marked sensitivity to paraquat of E. coli deficient in spermidine is of particular interest, since such mutants have no other phenotypic properties that can be easily assayed. This increased sensitivity has ...
The response regulator protein is a core element of two-component signaling pathway. In this study, we investigated functions of BRRG-1 of Botrytis cinerea, a gene that encodes a putative response regulator protein, which is homologous to Rrg-1 in Neurospora crassa. The BRRG-1 gene deletion mutant ?Brrg1-62 was unable to produce conidia. The mutant showed increased sensitivity to osmotic stress mediated by NaCl and KCl, and to oxidative stress generated by H2O2. Additionally, the mutant was more sensitive to the fungicides iprodione, fludioxonil, and triadimefon than the parental strain. Western-blot analysis showed that the Bos-2 protein, the putative downstream component of Brrg-1, was not phosphorylated in the ?Brrg1-62. Real-time polymerase chain reaction assays showed that expression ...
The electrochemical behaviour and fracture morphology of homogenized and sensitized type SAE 304 stainless steel U bent specimens, in 3% NaCl solution, at pH=2.0 and pH=7.0 both at room temperature and 100"0C was studied. Polarization curves, galvanostatic and potentiostatic experiments were run. It could be observed that high temperature and low pH favour transgranular cracking and longer sensitization times lower fracture time and tend to give rise to intergranular fracture. Light sensitization can produce transgranular cracking even at room temperature, when the homogenized alloy does not present stress-corrosion cracking for the same condition. (Author).
Somatostatin receptor scintigraphy (SRS) is a valuable method for the detection of somatostatin receptor-positive lesions. Most gastrinomas (over-)express the somatostatin receptor subtype 2 which can be targeted by In-111 labeled Octreotide. Different studies show a high sensitivity of SRS for the localization and staging of gastrinomas. SRS seems to be superior to other non-invasive imaging modalities and has been proven to significantly contribute to patient management. However, the sensitivity depends on the size and exact localization of the tumors. Smaller lesions and lesions located in the duodenum show a significantly lower sensitivity. In any case, SRS belongs to the routine imaging procedure for gastrinomas for localization and staging and can also be used for evaluation of the tumor progression. (author)
Abstract Lyme neuroborreliosis (LNB) is a serious but treatable disease. The diagnosis of LNB poses a challenge to clinicians, and improved tests are needed. The C6-peptide ELISA is frequently used on serum but not on cerebrospinal fluid (CSF). Data on the sensitivity of the C6-peptide ELISA in CSF in patients suffering from LNB have been conflicting. Serum-CSF pairs from 59 LNB patients, 36 Lyme non-neuroborreliosis cases, 69 infectious meningitis/encephalitis controls and 74 neurological controls were tested in a C6-peptide ELISA. With the optimal cut-off of 1.1, the sensitivity of the C6-peptide ELISA for LNB patients in CSF was 95%, and the specificity was 83% in the Lyme non-neuroborreliosis patients, 96% in the infectious controls, and 97% in the neurological controls. These results ...
A sensitive hydrogen peroxide (H2O2) sensor was fabricated based on graphene-Pt (GN-Pt) nanocomposite. The GN-Pt was synthesized by photochemical reduction of K2PtCl4 on GNs, and characterized by atomic force microscope (AFM), transmission electron microscope (TEM), and energy-dispersive X-ray spectroscopy (EDS). Electrochemical investigations indicated that the GN-Pt exhibited a high peak current and low overpotential towards the reduction of H2O2. The GN-Pt modified glass carbon electrode displayed a wide linear range (2-710mM), low limit of detection (0.5mM) and good selectivity for detection of H2O2 with a much higher sensitivity than that of Pt nanoparticles or graphene modified electrode.
Background: Quantifying HIV levels in mucosal secretions is essential to study compartmentalized expression of HIV and facilitate development of intervention strategies to prevent disease progression and transmission. Objectives: To develop a sensitive, reliable, and cost-effective technique to quantify HIV from blood and vaginal secretions that is compatible with efficient implementation in clinical research environments. Study design: A sensitive, reliable, internally-controlled real-time reverse transcriptase (RT) PCR assay, which uses the HIV-1 pol gene as a target (Hpol assay) was developed to quantify HIV levels in plasma and genital secretions, and compared to the widely used Roche Amplicor(TM) HIV-1 Monitor assay. In addition, a simplified method of sample collection and processing...
The authors have developed a high-sensitivity real-time neutron radiography (NR) system by the use of the low power reactor of Kinki University. The system was constructed with a high efficiency neutron-photon converter, an image intensifier and a SIT TELEVISION camera. Some digital image processing techniques were applied for improving the quality of the real-time neutron images. By the use of this system, dynamic neutron imaging was performed successfully under the condition of a weak neutron field that was about two orders of magnitude lower than that of the standard NR system. The neutron flux, calculated from the fluctuation of the neutron response of the images, was nearly equal to the value measured by the foil activation method. From this fact, the efficiency for the neutron detection of the imaging system was estimated to be almost 100%. For the purpose of developing a system with higher sensitivity, consideration of neutron statistics ...
The authors have developed a high-sensitivity real-time neutron radiography (NR) system by the use of the low power reactor of Kinki University. The system was constructed with a high efficiency neutron-photon converter, an image intensifier and a SIT TELEVISION camera. Some digital image processing techniques were applied for improving the quality of the real-time neutron images. By the use of this system, dynamic neutron imaging was performed successfully under the condition of a weak neutron field that was about two orders of magnitude lower than that of the standard NR system. The neutron flux, calculated from the fluctuation of the neutron response of the images, was nearly equal to the value measured by the foil activation method. From this fact, the efficiency for the neutron detection of the imaging system was estimated to be almost 100%. For the purpose of developing a system with higher sensitivity, consideration of neutron statistics ...
In order to develop a numerical tool for the fast evaluation of CANDU refuelling schemes, a Linear Sensitivity Matrix method (LSM) is developed. It assumes that all the effects caused by various perturbations to the core state are independent to each other and the core response to a perturbation is proportional to its magnitude. In this way, the main core parameters of a refuelling scheme can be derived by simple algebraic operations with the use of pre-calculated sensitivity matrices, without resorting to the complicated and time-consuming 3D core calculation. Verification against the Qinshan CANDU reactor operation history demonstrates that LSM is capable of generating accurate results and running very fast for evaluating a refuelling scheme. (authors)
A high sensitivity, high bandwidth, two-color interferometer (1064 and 532 nm) has been tested on the Hawk pulsed power generator at the Naval Research Laboratory. The phase resolution is 10"-"5 waves with a rise time of 3 ns, a new capability for diagnosing plasmas, and neutrals in pulsed power experiments. The two-color feature is used to distinguish phase shifts from free (plasma) electrons and bound (neutral and ion) electrons. Simultaneous electron and neutral density measurements were demonstrated in a plasma opening switch (POS) experiment. The ability to measure small phase shifts with fast rise time were demonstrated in a plasma filled diode experiment. The high sensitivity and vibration isolation enable neutral gas distribution measurements from supersonic nozzles used in plasma radiation source experiments. Examples of these measurements and future applications are described. copyright 1997 American Institute of Physics.
The term 'health/functional food' (HFF) refers to food supplements containing nutrients or other substances (in a concentrated form) that have a nutritional or physiological effect whose purpose is to supplement the normal diet. The Korean Health/Functional Food Act that came into effect in 2004 requires these products to be marketed in measured doses, such as in pills, tablets, capsules, and liquids. HFFs are of two types: generic and product-specific. There are 37 ingredients listed in the act for generic HFFs, and if an HFF contains a new active ingredient that is not included in the generic 37 products, it is considered a product-specific HFF. The standardization, safety, and efficacy of a new active ingredient are reviewed by the Korean Food and Drug Administration in order to receive approval as a product-specific HFF. Conforming with international standards and protecting public health requires constant upgrading of the Health/Functional Food Act.
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...
Non-linear optics encompasses a range of optical phenomena, including two- and three-photon fluorescence, second harmonic generation (SHG), sum frequency generation (SFG), difference frequency generation (DFG), third harmonic generation (THG), coherent anti-Stokes Raman scattering (CARS), and stimulated Raman scattering (SRS). The combined advantages of using these phenomena for imaging complex pharmaceutical systems include chemical and structural specificities, high optical spatial and temporal resolutions, no requirement for labels, and the ability to image in an aqueous environment. These features make such imaging well suited for a wide range of pharmaceutical and biopharmaceutical investigations, including material and dosage form characterisation, dosage form digestion and drug rele...
Objectives To delineate the safety and tolerability profile of methylphenidate and atomoxetine in children and adolescents with attention deficit hyperactivity disorder (ADHD) monitored for more than 1?year. Design A cohort study analyzing data from the national ADHD register on patients from the Lombardy Region treated with MPH or atomoxetine. Participants A total of 229 children (median age 11?years, range 6?17), enrolled in 15 regional centers between June 2007 and May 2010. Results The prevalence rate of pharmacological treatment for ADHD was 0.23%, whereas the estimated ADHD prevalence in the population was 0.95%. In total, 73.8% of patients had been treated with atomoxetine (10?90?mg daily) or MPH (10?75?mg daily); 22% of patients also received an additional psychotropic drug. Of the...
Various control procedures have been suggested for reducing foodborne infectious diseases. Receiving considerable attention is irradiation. This report estimates the medical and wage (or productivity) benefits associated with prevention of five human diseases transmitted by beef, pork, and chicken. (These diseases can also be transmitted by other vectors, such as eggs, milk, and pets. But these sources are not included in the analysis.) All of these foodborne infectious diseases - salmonellosis, campylobacteriosis, trichinosis, tapeworm, and toxoplasmosis - could be significantly reduced by irradiating meat and poultry. The Food and Drug Administration (FDA) has just approved irradiation of pork to prevent trichinosis (50FR 29658-59) and is considering approval of irradiation of chicken to kill Salmonella. 22 references.
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...
The degradation of irradiated human insulin in aqueous solutions was investigated in order to protect the protein against ionizing radiation. The influence of the drug concentration, excipients and irradiation temperature were studied.Aqueous solutions at pH 2 were irradiated by gamma rays or by accelerated electrons. Two different high-performance liquid chromatography (HPLC) methods were used: reverse-phase high-performance liquid chromatography (RP-HPLC)/UV and size exclusion liquid chromatography (SEC/UV) to investigate both the fragmentation and the formation of higher molecular weight proteins.In solution without excipients irradiated at ambient temperature at 10kGy, the loss of human insulin is almost complete. Addition of radio-protecting excipients (free radicals scavengers) and c...
Adipose tissue plays an essential role in energy homeostasis as a metabolic and endocrine organ. Accordingly, adipocytes are emerging as a major drug target 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...
Abstract Background: Dementia with Lewy bodies (DLB) is a common dementia of the elderly. A significant cholinergic deficit has been demonstrated that may be responsive to treatment by cholinesterase inhibitors (ChEIs). Methods: A 24-week, open-label study was designed to assess the efficacy and safety of a ChEI, galantamine, in 50 patients with DLB. Results: This study showed beneficial effects with galantamine in 2 of the 3 primary efficacy parameters. The scores on the Neuropsychiatric Inventory (NPI-12) improved by 8.24 points from baseline (p = 0.01) especially in visual hallucinations and nighttime behaviors (p = 0.004). The scores on the Clinician's Global Impression of Change improved by 0.5 points from baseline (p = 0.01). The third primary efficacy parameter, the Cognitive Drug R...
BACKGROUND AND PURPOSE In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the antidiabetic drug rosiglitazone in larger experimental animals. In the present study therefore concentration-dependent effects of rosiglitazone on action potential morphology and the underlying ion currents were studied in dog hearts. EXPERIMENTAL APPROACH Standard microelectrode techniques, conventional whole cell patch clamp and action potential voltage clamp techniques were applied in enzymatically dispersed ventricular cells from dog hearts. KEY RESULTS At concentrations -10-M rosiglitazone decreased the amplitude of phase-1 repolarization, reduced the maximum velocity of depolarization and caused depression of the plateau potential. These effects d...
Abstract Lysis and extraction of cells are essential sample processing steps for investigations pertaining to metabolism of xenobiotics in cell culture studies. Of particular importance to these procedures are maintaining high lysis efficiency and analyte integrity as they influence the qualitative and quantitative distribution of drug and toxicant metabolites in the intra- and extracellular milieus. In this study we have compared the efficiency of different procedures viz. homogenization, sonication, bead beating, and molecular grinding resin treatment for disruption of HT-29 colon cells exposed to benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound and a suspected colon carcinogen. Also, we have evaluated the efficiency of various procedures for extracting BaP parent c...
Most active pharmaceutical ingredients (API) exhibit particle size distributions with some degrees of asymmetry deviating from log-normality. A new log-skew-normal (L-S-N) distribution model is proposed for a systematic comparison of the asymmetry effect on content uniformity. The new model originated from the S-N model used by Azzalini gives a close approximation to real API particle size distribution. Monte-Carlo method was employed to simulate the dosage potency distribution. A high risk of over potency is uncovered when either the dose is low or API particle size distribution is positively skewed. This is due to the formation of pseudo heavy tail in potency distribution that decays slower than exponentially. Nomographs of API particle size versus dosage strength were constructed with a...