SEARCH · PubMed Health

Results for “CodY”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources

PubMed2006

An implantable carotid sinus stimulator for drug-resistant hypertension: surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial.

BACKGROUND: A large number of patients have hypertension that is resistant to currently available pharmacologic therapy. Electrical stimulation of the carotid sinus baroreflex system has been shown to produce significant chronic blood pressure decreases in animals. The phase II Rheos Feasibility Trial was performed to assess the response of patients with multidrug-resistant hypertension to such stimulation. METHODS: The system consists of an implantable pulse generator with bilateral perivascular carotid sinus leads. Implantation is performed bilaterally with patients under narcotic anesthesia (to preserve the reflex for assessment of optimal lead placement). Dose-response testing at 0 to 6 V is assessed before discharge and at monthly intervals thereafter; the device is activated after 1 month's recovery time. This was a Food and Drug Administration-monitored phase II trial performed at five centers in the United States. RESULTS: Ten patients with resistant hypertension (taking a median of six antihypertensive medications) underwent implantation. All 10 were successful, with no significant morbidity. The mean procedure time was 198 minutes. There were no adverse events attributable to the device. Predischarge dose-response testing revealed consistent (r = .88) reductions in systolic blood pressure of 41 mm Hg (mean fall is from 180-139 mm Hg), with a peak response at 4.8 V (P < .001) and without significant bradycardia or bothersome symptoms. CONCLUSIONS: A surgically implantable device for electrical stimulation of the carotid baroreflex system can be placed safely and produces a significant acute decrease in blood pressure without significant side effects.

Adult↗

PubMed2006

Environmental induction of CYP1A-, CYP2M1- and CYP2K1-like proteins in tropical fish species by produced formation water on the northwest shelf of Australia.

Normal operation of oil well platforms results in the discharge of "produced formation water" (PFW). The expression of CYP1A, CYP2M1- and 2K1-like proteins was examined for use as possible biomarkers of PFW exposure. A pilot study at the Harriet A production platform, on the Northwest Shelf of Australia, had indicated that PFW contamination possibly contributes to induction of CYP1A- and 2K1/2M1-like proteins in Gold-Spotted Trevally (Carangoides fulvoguttatus). In a subsequent caged fish study in the same location, Stripey seaperch (Lutjanus carponotatus) were caught at a clean site, then distributed to three caging sites: A (near-field), B (far-field) and C (a non-impacted reference site). Fish were sampled at time T = 0, 3 and 10 days. Significant increases of CYP1A, one CYP2K1- and two CYP2M1-like proteins were noted at Site A at T = 10. For another CYP2K1-like protein, a significant increase was observed at Site A only at T = 3. Prevailing winds changed between days 6 and 8 of sampling, moving the surface water plume directly west, possibly impacting in situ PFW exposure. The results indicate that tropical fish CYP1A protein is sensitive to PFW exposure. Importantly, statistically significant environmental induction of both CYP2M1- and CYP2K1-like proteins in tropical fish due to PFW exposure had not previously been described and CYP2 family induction may represent possible new biomarkers (other than CYP1A) of PFW exposure. In addition, the novel fraction-specific response of CYP2K-like proteins requires further verification but offers promise for improved monitoring of sub-lethal responses in marine organisms. (Supported by Australian Institute of Marine Science, Apache Energy Ltd. and the Environmental Toxicology Research Program at The University of Mississippi).

Animals↗

PubMed2005

Summary results from a pilot study conducted around an oil production platform on the Northwest Shelf of Australia.

The Australian Institute of Marine Science (AIMS) conducted a pilot study around the Harriet A oil production platform on the Northwest Shelf of Australia. We evaluated hepatic ethoxyresorufin-O-deethylase (EROD) activity, fluorescent aromatic compounds (FACs) in bile and immunodetection of CYP1A-like proteins in two Australian tropical fish species, Gold-Spotted Trevally (Carangoides fulvoguttatus) and Bar-Cheeked Coral Trout (Plectropomus maculatus) to assess exposure to petroleum hydrocarbons associated with produced formation water (PFW). Additionally, the incidence of hydrocarbon-degrading bacteria isolated from the liver and bile of all fish captured was examined. Low EROD activity was found in both species, with EROD activity in C. fulvoguttatus showing significant site differences. FACs and CYP1A protein levels in C. fulvoguttatus showed a clear trend in hydrocarbon exposure consistent with hydrocarbon chemistry data: Harriet A>Harriet C>reference site. P. maculatus showed elevated levels of FACs at Harriet A as compared to the reference site and demonstrated detectable levels of CYP1A-like proteins at these two sites. Hydrocarbon-degrading bacteria were found in the liver and bile of both species, yet there was no correlation by sites. Our results demonstrate that C. fulvoguttatus and P. maculatus have potential as indicator species for assessing the effects from exposure to petroleum hydrocarbons. Both FACs and CYP1A are providing warning signs that there is potential for biological effects on fish populations exposed to PFW around the Harriet A production platform.

Analysis of Variance↗

PubMed2004

Updating a 3-D vertebral body finite element model using 2-D images.

In osteoporotic patients, vertebral strength is often evaluated in the clinical setting using bone densitometry methods, such as dual energy X-ray absorptiometry. Finite element models based on computed tomography (CT) have been shown to outperform such methods in predicting fracture strength, but repetitive use of CT scans may be impractical due to cost, availability, and radiation exposure. We propose a method of generating a vertebral model at an initial time point which can subsequently be updated using several digital radiographs by using an algebraic reconstruction technique (ART) to find the three-dimensional density distribution. The effectiveness of the algorithm was measured by comparison of the error of the reconstructed model to the error incurred by using the outdated model. Application of the ART was able to reduce density errors from 30% to under 7% and to reduce errors in calculated vertebral stiffness from 125% to under 10%. This preliminary study demonstrates that the method is valid and could potentially improve fracture risk diagnostics drastically.

Absorptiometry, Photon↗

PubMed2005

Selective angiotensin II receptor antagonism enhances whole-body insulin sensitivity and muscle glucose transport in hypertensive TG(mREN2)27 rats.

Essential hypertension is frequently associated with insulin resistance of skeletal muscle glucose transport, and angiotensin II (ANGII) can contribute to the pathogenesis of both conditions. The male heterozygous TG(mREN2)27 rat (TGR) harbors the mouse transgene for renin, exhibits local tissue elevations in ANGII and is an excellent model of both hypertension and insulin resistance associated with defective insulin signaling. The present study was designed to assess the specific role of ANGII in the insulin resistance of the male heterozygous TGR. TGRs were treated with either vehicle or the ANGII (AT(1)-specific) receptor antagonist, irbesartan (50 mg/kg body weight), for 21 consecutive days. Compared with vehicle-treated TGRs, whole-body insulin sensitivity was increased 35% (P < .05) in the irbesartan-treated group, and insulin-mediated glucose transport was increased (P < .05) in both type IIb epitrochlearis (80%) and type I soleus (59%) muscles after irbesartan treatment. Moreover, glycogen synthase activation due to insulin was increased 58% (P < .05) in the soleus of the irbesartan-treated TGRs. However, no significant improvements were observed for functionality of insulin-signaling elements (tyrosine phosphorylation of insulin receptor and insulin receptor substrate 1 [IRS1], IRS1 associated with the p85 regulatory subunit of phosphatidylinositol 3'-kinase, and Ser473 of Akt) in muscle of irbesartan-treated animals, except for a 25% increase (P < .05) in IRS1 tyrosine phosphorylation in soleus. Collectively, these data indicate that the improvements in whole-body and skeletal muscle insulin action after long-term antagonism of ANGII action in TGRs occur independently of modulation of the functionality of these insulin-signaling elements.

Angiotensin II↗

PubMed2006

Are oxidative mechanisms primary in ethanol induced Purkinje neuron death of the neonatal rat?

Rat cerebellar Purkinje neurons are vulnerable to ethanol exposure during the brain growth spurt, especially during early postnatal exposure. A prominent hypothesis is that ethanol induces oxidative types of alterations that result in the neurodegeneration. The purpose of this study was to test this hypothesis in two ways. One was to determine if the reactive oxidative species, nitrotyrosine (NT), was produced in the cerebellum following ethanol exposure. Second, was to determine if co-administration of the clinically useful antioxidant N-acetylcysteine (NAC) afforded any protection from Purkinje neuron loss. Rat pups were treated on postnatal day 4 with a single ethanol (6.0 g/kg) or isocaloric intragastric intubation. The cerebelli were analyzed for NT with ELISA assays at 2, 4, 6, or 8 h following the single exposure. No evidence of NT was found at any of these time points. Another group of animals received ethanol exposure on PN4, or ethanol exposure plus NAC. Control groups included isocaloric intubated controls (IC), IC plus NAC, and mother reared controls. Twenty-four hours following the exposures, the pups were perfused and the cerebellum processed for cell counting. Ethanol exposure reduced the number of Purkinje neurons in the cerebellum. Concurrent treatment with antioxidant did not protect the Purkinje neurons from ethanol-related cell loss. These in vivo analyses do not support a robust oxidative mechanism involving the production of reactive nitrogen species as a significant means of Purkinje cell neurodegeneration.

Acetylcysteine↗

PubMed2006

User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability.

Active contour segmentation and its robust implementation using level set methods are well-established theoretical approaches that have been studied thoroughly in the image analysis literature. Despite the existence of these powerful segmentation methods, the needs of clinical research continue to be fulfilled, to a large extent, using slice-by-slice manual tracing. To bridge the gap between methodological advances and clinical routine, we developed an open source application called ITK-SNAP, which is intended to make level set segmentation easily accessible to a wide range of users, including those with little or no mathematical expertise. This paper describes the methods and software engineering philosophy behind this new tool and provides the results of validation experiments performed in the context of an ongoing child autism neuroimaging study. The validation establishes SNAP intrarater and interrater reliability and overlap error statistics for the caudate nucleus and finds that SNAP is a highly reliable and efficient alternative to manual tracing. Analogous results for lateral ventricle segmentation are provided.

Brain↗

PubMed2004

Strabismus following posterior segment surgery.

Persistent diplopia following posterior segment surgery is not uncommon. There are several causes of postoperative strabismus, some of which are preventable. Knowledge of the possible causes, proper evaluation, and appropriate treatment can eliminate or at least reduce the morbidity from this unwelcome postoperative surprise.

Humans↗

PubMed2004

Femoral head blood flow reduction and hypercoagulability under 24 h megadose steroid treatment in pigs.

The pathogenesis of corticosteroid-induced femoral head necrosis is assumed to be ischemia. The purpose of this study was to investigate the perfusion pattern of the femoral head and plasma coagulability during 24 h corticosteroid megadose treatment, as recommended by the National Acute Spinal Cord Injury Studies (NASCIS), in the awake big animal model. Blindedly, 9 animals underwent megadose methylprednisolone infusion (30 mg/kg intravenously as an initial bolus, followed by 5.4 mg/kg/h for further 23 h) while 9 animals served as placebo treated controls. Regional blood flow of the systematically subdivided femoral head, proximal femur, acetabulum, and soft tissue hip regions was investigated by the microsphere technique at steady state (phase 1), after the initial bolus infusion (phase 2), and after the completed treatment (phase 3). Plasma coagulability was examined in phases 1 and 3. Blood flow of the femoral head epiphysis and metaphyseal cancellous bone was unchanged after one hour of steroid infusion, but decreased after the completed treatment at 24 h in the experimental group. Femoral head blood flow reduction was global without a tendency to more pronounced blood flow decrease in any subregion. Plasma fibrinogen was significantly higher after 24 h of steroid infusion than in the placebo control group. 24 h high dose methylprednisolone treatment causes femoral head blood flow reduction and hypercoagulability of plasma in the normal awake immature pig. These findings may be pathogenetic factors in the early stage of steroid-induced osteonecrosis.

Animals↗

PubMed2005

Reducing the impact of viral respiratory infections in children.

This article reviews the epidemiology and clinical aspects of the major viral causes of upper and lower respiratory tract disease in children. Particular emphasis is placed on prevention and control of viral disease through the use of vaccines and antiviral agents. Evolution of new viral pathogens, such as avian influenza virus and the SARS-CoV, are discussed.

Age Distribution↗

PubMed2005

Purification and characterization of human-derived Pneumocystis jirovecii dihydrofolate reductase expressed in Sf21 insect cells and in Escherichia coli.

Pneumonia caused by Pneumocystis jirovecii is still a major opportunistic infection among patients with AIDS. This opportunitistic pathogen is susceptible to therapy with inhibitors of the enzyme dihydrofolate reductase (DHFR) that target cell growth. Recent studies have shown that recombinant human-derived Pneumocystis DHFR (pDHFR) differs from rat-derived pDHFR by 38% in amino acid sequence. However, characterization of drug susceptibility, kinetics, and the three-dimensional structure of human-derived pDHFR has been hampered by the limited availability of purified material. The present study was undertaken to develop procedures to prepare sufficient enzyme for structure/function studies. Protein yield was limited when human-derived pDHFR was expressed in Escherichia coli using a pET28a(+) vector with an N-terminal His-tag for the 25 kDa protein. Therefore, the protein was expressed in Sf21 insect cells by baculovirus infection. The soluble enzyme was purified from cell lysates via Ni-chelated chromatographic columns, yielding about 5.1 mg of human-derived pDHFR fusion protein per liter of Sf21 culture. The purified protein had the expected mass as determined from Western blots with antibody for the N-terminal His-tag. This His-tagged recombinant DHFR from human-derived Pneumocystis was catalytically active and demonstrated kinetics similar to the recombinant enzyme from rat-derived Pneumocystis. The present studies for production of soluble human-derived pDHFR indicated that the baculovirus expression system supported production of significantly purer catalytically active enzyme in higher yields than that expressed in bacterial cultures. These protocols now make it possible to facilitate screening of antifolates with selectivity for human-derived pDHFR and to determine its three-dimensional structure.

Animals↗

PubMed2005

Research use in children's mental health policy in Canada: maintaining vigilance amid ambiguity.

Many researchers hope to see the best available research evidence used in policy-making to address important public problems. However, policy often appears to be based on anything but the research evidence, as the problem of conduct disorder (or severe antisocial behaviour in children) shows. In Canada, few children receive effective prevention or treatment programs, and incarceration is overused, despite evidence that it is ineffective and potentially harmful. Using the example of conduct disorder, we investigated why policy-making has not reflected the research evidence, examining research use in the context of competing influences on the policy process. Qualitative methods were used to analyze data from interviews with thirty-two politicians and senior civil servants. Our allegiance to rationality wavered as we listened to policy-makers who contended with the inherent ambiguity in the policy process. They told us that they managed institutional constraints including fragmentation across levels and sectors of government, and the long-term effects of fiscal restraint. They also reconciled the competing interests of stakeholders' priorities, the public's response to negative events involving children and the media's role in shaping this response. Ideas about youth violence were morally charged, but policy-makers remained committed to improving children's lives. Day-to-day, policy-makers obtained most of their information internally and informally. Research evidence was valued and used, but as just one source of ideas and information among many. In this environment of ambiguity, creative civil servants formed partnerships with trusted researchers in order to change policy. Our findings suggest that the use of research evidence in policy-making could be enhanced if researchers learned about the competing influences on the policy process, formed research-policy partnerships, challenged the incentives within research institutions, and engaged in public debates about important problems, such as child antisocial behaviour.

Child↗

PubMed2006

Molecular modeling of the thyroid hormone interactions with alpha v beta 3 integrin.

A cell surface receptor for thyroid hormone has recently been identified on the extracellular domain of integrin alphavbeta3. In a variety of human and animal cell lines this hormone receptor mediates activation by thyroid hormone of the cellular mitogen-activated protein kinase (MAPK) signal transduction cascade. An arginine-glycine-aspartate (RGD) recognition site on the heterodimeric integrin is essential to the binding of a variety of extracellular matrix proteins. Recent competition data reveal that RGD peptides block hormone-binding by the integrin and consequent MAPK activation, suggesting that the hormone interaction site is located at or near the RGD recognition site on integrin alphavbeta3. A deaminated thyroid hormone (l-thyroxine, T4) analogue, tetraiodothyroacetic acid (tetrac, T4ac), inhibits binding of T4 and 3,5,3'-triiodo-l-thyronine (T3) to alphavbeta3, but does not activate MAPK. Structural data show that the RGD cyclic peptide binds at the interface of the propeller of the alphav and the B domains on the integrin head [Xiong JP, Stehle T, Zhang R, Joachimiack A, Frech M, Goodman SL, et al. Crystal structure of the extracellular segment of integrin alphavbeta3 in complexing with an Arg-Gly-Asp ligand. Science 2002;296:151-5]. To model potential interactions of thyroid hormone analogues with integrin, we mapped T4 and T4ac to the binding site of the RGD peptide. Modeling studies indicate that there is sufficient space in the cavity for the thyroid hormone to bind. Since the hormone is smaller in overall length than the RGD peptide, the hormone does not interact with the Arg recognition site in the propeller domain from alphav. In this model, most of the hormone interactions are with betaA domain of the integrin. Mutagenic studies can be carried out to validate the role of these residues in directing hormone interactions.

Integrin alphaVbeta3↗

PubMed2005

Membrane receptors mediating thyroid hormone action.

A recently identified thyroid hormone cell surface receptor on the extracellular domain of integrin alphaVbeta3 leads in human cell lines to activation of the mitogen-activated protein kinase (MAPK) signal transduction cascade. Examples of MAPK-dependent thyroid hormone actions are plasma membrane ion pump stimulation and specific nuclear events. These events include serine phosphorylation of the nuclear thyroid hormone receptor, leading to coactivator protein recruitment and complex tissue responses, such as thyroid hormone-induced angiogenesis or tumor cell growth. The existence of this cell surface receptor means that the activity of administered hormone could be limited through structural modification of the molecule to reproduce or inhibit only those hormone actions initiated at the cell surface. Examples of such modifications are provided.

Animals↗

PubMed2026

DipTRANS: an improved method for in planta transformation and genome engineering in Nicotiana benthamiana.

Plant transformation remains constrained by labor-intensive tissue culture. Our previous work showed that direct delivery of developmental regulators (DRs) can induce de novo meristems on plants, offering a promising transformation approach. In this resource article, we introduced DipTRANS (Direct in planta Transformation), an optimized, soil-based heritable transformation platform for Nicotiana benthamiana that bypasses sterile culture entirely. DipTRANS is built on DR-induced de novo meristem formation. After optimizing parameters, including regulator combinations, Agrobacterium strain, and infiltration density, DipTRANS yielded transformation efficiencies to 46.7%. Developmental abnormalities associated with regulator expression are resolved through cutting-based propagation and virus-induced transgene excision, enabling recovery of fertile, transgenic progeny. Furthermore, DipTRANS supports tissue culture-free, transgene-free iterative genome modification via virus-induced genome editing. Overall, DipTRANS enables the generation of transgenic plants within 30 days and engineered progeny within 90 days. This methodology provides a rapid, versatile platform and a blueprint for extending direct in planta transformation to other plant species.

DRs↗

PubMed2005

Generation of dendritic cells from rabbit bone marrow mononuclear cell cultures supplemented with hGM-CSF and hIL-4.

The in vitro generation of dendritic cells (DCs) from either blood or bone marrow has been accomplished for humans and a number of other species. This ability has facilitated the opportunity to test the efficacy of DC vaccines in various tumor models. The cottontail rabbit papillomavirus (CRPV) model is the most clinically relevant animal model for human papillomavirus (HPV)-associated carcinogenesis. The CRPV model has been used to test various preventative and therapeutic vaccination strategies, and the availability of rabbit DCs would further expand its utility. However, to date, rabbit DCs have not been phenotypically and/or functionally characterized. Here we show that DCs can be generated in vitro from rabbit bone marrow mononuclear cells (BMMCs) cultured in the presence of the human cytokines GM-CSF and IL-4 and matured with lipopolysaccharide (LPS). These cells show upregulation of MHC class II and CD86, as well as downregulation of CD14, do not have non-specific esterase activity, are able to perform receptor-mediated endocytosis, and are potent stimulators of allogeneic T cell proliferation in mixed lymphocyte reactions. The ability to generate rabbit DCs makes it possible to test the efficacy of DC vaccination in the prevention and treatment of CRPV-induced lesions, which may provide useful preclinical data regarding the use of DC vaccines for HPV-associated lesions, including cervical cancer.

Animals↗

PubMed2004

Efficacy of a single milbemycin oxime administration in combination with praziquantel against experimentally induced heartworm (Dirofilaria immitis) infection in cats.

The efficacy of a combination of milbemycin oxime and praziquantel in preventing the establishment of experimentally induced heartworm (Dirofilaria immitis) infection was investigated in a study involving 24 young domestic short-hair cats. The animals were inoculated with 50 infective larvae on day 0. Subsequently they were divided into two groups of 12 animals each. The animals in group 1 were treated once with medicated tablets containing 4 mg milbemycin (minimum dose 2 mg/kg body weight) and 10 mg praziquantel (MILBEMAX) on day 30 after infection. Cats in group 2 received placebo tablets on the same day. On day 183 post-infection a blood sample was taken from each animal before euthanasia and necropsy. The blood samples were tested for the presence of microfilariae and the necropsied animals were examined for the presence of adult worms. Microfilariae were not found in any of the investigated cats. No heartworms were found in the animals in group 1 (treated with medicated tablets). Out of the 12 placebo-treated cats 1 was heartworm-free, whereas all the others were found to be infected with 1-3 adult heartworms.

Animals↗

PubMed2006

Comparative effects of milbemycin oxime-based and febantel-pyrantel embonate-based anthelmintic tablets on Toxocara canis egg shedding in naturally infected pups.

The effect of two treatment programmes on egg shedding in dogs naturally infected with Toxocara canis, one based on a milbemycin oxime-praziquantel-lufenuron combination (SENTINEL) Spectrum; Group 1) and the other based on a febantel-pyrantel embonate-praziquantel combination (DRONTAL) Plus; Group 2), was compared in a study involving 104 suckling pups from three different kennels. The animals in Group 1 were treated at a minimum milbemycin oxime dose of 0.5 mg/kg bw starting at 2 weeks of age and subsequently every 4 weeks until reaching 26 weeks of age. The animals in Group 2 were treated every 2 weeks from week 2 until week 12 of age and then once at week 26 at a minimum febantel and pyrantel embonate dose of 15.0 and 14.4 mg/kg bw, respectively. Toxocara egg counts were determined fortnightly starting at 2 weeks of age and continuing until 26 weeks of age for every pup. Any adverse drug event was recorded during the trial. Both treatment programmes significantly reduced the zoonotic Toxocara egg shedding and were well tolerated by the pups. The pups in Group 1 showed lower average faecal egg counts and were found more frequently shedding no eggs than the pups in Group 2.

Animals↗