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PubMed2003

Co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex induced by clozapine, the prototype atypical antipsychotic.

RATIONALE: Clozapine has been shown to increase extracellular dopamine (DA) and noradrenaline (NA) in the medial prefrontal cortex (mPFC). A recent study of ours suggested that extracellular DA in the PFC originates not only from dopaminergic but also from noradrenergic terminals, its release being controlled by alpha(2)-adrenoceptors. OBJECTIVES: Since clozapine binds to alpha(2)-adrenoceptors, the possibility that it might co-release DA and NA was studied. METHODS: By means of microdialysis coupled to HPLC with electrochemical detection, the effect of clozapine on extracellular DA and NA in the mPFC, densely innervated by DA and NA, was compared to that in the occipital cortex, equally innervated by NA but receiving few DA projections. RESULTS: Extracellular NA was found to be the same in the two cortices, consistent with homogeneous NA innervation. On the other hand, extracellular DA in the occipital cortex was only 29% lower than in the mPFC, in spite of the scarce dopaminergic innervation in the occipital cortex. Clozapine (10 mg/kg IP) increased extracellular DA and NA not only in the mPFC (by about 320% and 290%, respectively) but also in the occipital cortex (by 560% and 230%, respectively). Administration of the alpha(2)-agonist clonidine (0.15 mg/kg) reversed the effect of clozapine in both cortices, while the D(2)-agonist quinpirole (0.1 mg/kg IP) was ineffective. CONCLUSIONS: The results suggest that clozapine, by inhibiting alpha(2)-adrenoceptors, co-releases DA and NA from noradrenergic terminals in the occipital cortex and that the same mechanism might be responsible for the concomitant increase of the two monoamines in the mPFC.

Adrenergic alpha-Agonists↗
PubMed1998

Technetium-99m Q4: a prototype cationic perfusion radiotracer with myocardial washout.

Technetium-99m Q4 is derived from an existing mixed ligand myocardial tracer (99mTc-Q3) by the addition of an ester group to promote myocardial washout. Six subjects with single-vessel coronary disease documented by angiography and/or Q wave myocardial infarction documented by electrocardiography were studied with 99mTc-Q4 injection during exercise and with comparative thallium-201 tomography. Six healthy volunteers were also studied with 99mTc-Q4 imaging following injection at peak exercise. Tomographic images with 99mTc-Q4 and 201Tl each provided correct assessment of the presence or absence of coronary disease in 22 of 30 myocardial segments (73.3%). Six myocardial segments showed defect reversibility with 99mTc-Q4, whereas 14 segments showed reversibility with 201Tl, but the latter included three segments with no angiographic or electrocardiographic evidence of disease. In both normals and subjects with coronary artery disease, significant global washout of 99mTc-Q4 was observed over 4 h. For five patients with angiographic evidence of unrevascularized coronary artery stenosis, the ischemic to normal zone count ratio increased from 0. 782+/-0.107 at 45 min postexercise to 0.891+/-0.115 at 4 h postexercise (P = 0.016), suggesting occurrence of differential washout. It is concluded that addition of an ester group functionality to a previously studied mixed ligand cardiac tracer promotes global and regional myocardial tracer washout. Nevertheless, demonstration of perfusion defect reversibility with comparable frequency to that observed with 201Tl stress and reinjection images, required separate injections of 99mTc-Q4 at peak stress and at rest.

Adult↗
PubMed2000

Forest Protection and Reforestation in Costa Rica: Evaluation of a Clean Development Mechanism Prototype.

/ Costa Rica has recently established a program that provides funds for reforestation and forest protection on private lands, partly through the sale of carbon certificates to industrialized countries. Countries purchasing these carbon offsets hope one day to receive credit against their own commitments to limit emissions of greenhouse gases. Costa Rica has used the proceeds of the sale of carbon offsets to Norway to help finance this forest incentive program, called the Private Forestry Project, which pays thousands of participants to reforest or protect forest on their lands. The Private Forestry Project is accompanied by a monitoring program conducted by Costa Rican forest engineers that seeks to determine net carbon storage accomplished on these lands each year. The Private Forestry Project, which is officially registered as an Activity Implemented Jointly, is a possible model for bundled projects funded by the Clean Development Mechanism (CDM) established by the 1997 Kyoto Protocol to the UN Framework Convention on Climate Change. It also serves as an interesting example for the CDM because it was designed by a developing country host-not by an industrialized country investor. Accordingly, it reflects the particular "sustainable development" objectives of the host country or at least the host planners. Early experience in implementing the Private Forestry Project is evaluated in light of the main objectives of the CDM and its precursor-Activities Implemented Jointly. It is concluded that the project appears to meet the criteria of global cost-effectiveness and financing from non-ODA sources. The sustainable development implications of the project are specific to the region and would not necessarily match the ideals of all investing and developing countries. The project may be seen to achieve additional greenhouse gas abatement when compared against some (although not all) baselines.

Journal Article↗
PubMed2006

Properties of the prototype 256-row (cone beam) CT scanner.

We evaluated Feldkamp artifacts, which are specific to cone-beam computed tomography (CT), in phantom and clinical studies using the 256-multidetector-row CT (256MDCT), and compared the reconstruction accuracy of axial and helical scans. Image noise, slice sensitivity profile (SSP) and artifacts with the 256MDCT were evaluated using a phantom, and the results were compared to those of a 64MDCT. We also examined chest and abdomen scans produced with the 256MDCT in volunteers. For the axial scan, Feldkamp artifacts were visualized as high-frequency streak-like artifacts that are oriented horizontally at the edge of the scan region in the phantom study. Similar results were obtained with the volunteers in soft-tissue regions near either bony structures or air pockets. Feldkamp artifacts with the 256MDCT can lead to misdiagnosis if not correctly identified and minimized via helical scanning. Image noise was less for axial than helical scans, while SSP was better with helical than axial scans. Feldkamp artifacts observed in the 256MDCT images, however, did not generally affect the interpretation of images. The 256MDCT promises more accurate diagnosis, and will provide volumetric cine images of wider cranio-caudal coverage, enabling new applications of CT.

Adult↗
PubMed1997

Rapid prototyping (stereolithography) in the management of intra-articular calcaneal fractures.

The purpose of this study was to evaluate and compare the diagnostic performance of stereolithography vs workstation-based three-dimensional (3D) reformations in intra-articular calcaneal fractures. A total of 30 intra-articular calcaneal fractures were examined using standard radiographs, coronal CT scans, and 2D and 3D reformations. The CT data were transferred to an outside institution, and stereolithograms were produced from photopolymer resin employing a laser beam system. 3D reformations and stereolithograms were analyzed in a blinded fashion by two staff radiologists. Receiver-operating-characteristic (ROC) curves were obtained for six clinically significant fracture components. Standard radiographs, coronal CT scans, and 2D reformations served as the standard of reference. The area under the ROC curves for 3D reformations and stereolithograms were 1.0 and 0.98 for abnormal tuber angles, 0.91 and 0.91 for anterior and middle talo-calcaneal joint involvement, 0. 90 and 0.95 for involvement of the posterior talo-calcaneal joint, 0. 65 and 0.78 for the presence of a lateral bulge, 0.80 and 0.81 for the involvement of the calcaneocuboidal joint, and 0.62 and 0.67 for the presence of a "tongue-type" fracture. No statistically significant difference was demonstrated for the two methods (Wilcoxon signed-rank test, p = 0.138). Based on our results stereolithograms did not prove to be statistically superior to workstation-based 3D reformations. Stereolithograms may still be useful for teaching purposes and for surgical planning at a thinking-efficacy level.

Adult↗
PubMed2005

Search for new prototypes for the chemotherapy of filariasis: a chemotherapeutic and biochemical approach.

The antifilarial activity of two coumarin derivatives (A, B) and three glycosyl amine derivatives (D, E, F) was evaluated against a subperiodic strain of human lymphatic filarial parasite Brugia malayi by the intraperitoneal route at 50 mg/kg for 5 consecutive days. Of these, the two sugar derivatives (D and E) were selected for evaluation by the oral route based on their microfilaricidal (mild), macrofilaricidal and female worm sterilization efficacy using the i.p. route of administration. Compound E was finally selected for combination therapy on the basis of its microfilaricidal and embryostatic action by the oral route and its spectrum of activity against micro- and macrofilariae including embryostatic activity by the i.p. route. In addition, E also significantly inhibited the parasite DNA topoisomerase II. Compound A, in contrast, led to an enhanced adult worm burden. Compound B was toxic by the i.p. route, killing all of the treated animals before completion of the experiment. Some of these compounds demonstrated significant antifilarial efficacy of varying degree when tested in vitro Compounds B, D and F also killed adult B. malayi in vitro at 100 muM while 50 muM resulted in very slow motility of worms. Compound E in combination with a promising macrofilaricidal benzopyran derivative reported by us recently (compound C) did not show any synergistic or additive effect. These two compounds (C and E) individually on oral administration with either DEC or ivermectin significantly improved microfilaricidal efficacy in terms of intensity and duration of suppressed microfilaraemia. The combination of DEC with compound E demonstrated marginal enhancement in adulticidal efficacy, however, the embryostatic effect of the duo was significantly higher than that exerted by the individual agents. It may thus be inferred that in the absence of an adulticidal antifilarial drug, the use of potential antifilarials in combination with the standard filaricides may yield better results.

Amines↗
PubMed2006

Performance of a prototype baited-trap in attracting and infecting the tick Amblyomma variegatum (Acari: Ixodidae) in field experiments.

Investigations were commenced to study the potential use of the fungi, Beauveria bassiana, Metarhizium anisopliae, and the attraction-aggregation-attachment pheromone (AAAP) for the control of Ambloyomma variegatum as an environmentally friendly technology. The objective of the study was to develop and test a device, which could be used for pheromone and carbon dioxide delivery and infection of ticks with the fungi in an attempt to control the tick populations in the vegetation. Using a pheromone-baited device treated with the fungi mixture, 79% of the ticks released were attracted and exposed to the fungi and of these, 78% died during incubation in the laboratory. In another set of experiments, of the released ticks that were similarly exposed to fungi using the pheromone-baited device and left in the vegetation, 33.8% were recovered compared to recoveries of between 76 and 84% in the controls. These results were significantly different at the 5% level, an indication that the pheromone/fungi mixtures had significant effect in reducing the tick population in the field.

Animals↗
PubMed2004

Caffeine suppresses metastasis in a transgenic mouse model: a prototype molecule for prophylaxis of metastasis.

A significant fraction of cancer patients have occult disseminated tumors at the time of primary diagnosis, which usually progress to become clinically relevant lesions. Since the majority of cancer mortality is associated with metastatic disease, the ability to inhibit the growth of the secondary tumors would significantly reduce cancer-related morbidity and mortality. We have investigated whether caffeine, which has been shown to suppress tumor cell invasiveness and experimental metastasis, can suppress metastasis in a spontaneous transgene-induced mammary tumor model. Chronic exposure to caffeine prior to the appearance of palpable mammary tumors significantly reduced both tumor burden and metastatic colonization. However, when caffeine exposure began after the appearance of frank tumors, caffeine suppressed metastasis without changing primary tumor burden. The means by which caffeine suppressed metastatic activity may be associated with inhibition of malignant transformation of mammary epithelial cells, inhibition of conversion of dormant tumor cells to micrometastases, micrometastases to macrometastases, or inhibition of tumor cell adhesion and motility. Gene and protein expression patterns resulting from caffeine treatment showed that metastasis suppression may be associated with up-regulation the mRNA expression of multiple extracellular matrix genes, including Fbln1, Bgn, Sparc, Fbn1, Loxl1, Colla1, Col3a1, Col5a1, ColS5a2, ColSa3, Col6a1, Col6a2, and Col6a3. These data suggested that caffeine or other methyl xanthine derivatives may improve the clinical outcome in patients prior to and following the diagnosis of metastatic disease, and could potentially reduce the morbidity and mortality associated with disseminated tumors.

Animals↗
PubMed2007

Rules versus prototype matching: strategies of perception of emotional facial expressions in the autism spectrum.

When perceiving emotional facial expressions, people with autistic spectrum disorders (ASD) appear to focus on individual facial features rather than configurations. This paper tests whether individuals with ASD use these features in a rule-based strategy of emotional perception, rather than a typical, template-based strategy by considering outcome implications of these strategies. Rule-based strategies are more tolerant of extreme stimuli than are template-based ones. Tolerance for exaggerated emotional facial expressions in individuals with ASD compared to IQ and education matched controls was tested in a forced-choice paradigm. For five of six emotions, those with ASD were more likely to accept the most exaggerated images as most realistic. People with ASD appear to rely more heavily on a rule-based strategy than a template-based strategy in perceiving emotional facial expressions.

Adolescent↗
PubMed2006

Oscillations and waves of cyclic AMP in Dictyostelium: a prototype for spatio-temporal organization and pulsatile intercellular communication.

The amoebae Dictyostelium discoideum aggregate after starvation in a wavelike manner in response to periodic pulses of cyclic AMP (cAMP) secreted by cells which behave as aggregation centers. In addition to autonomous oscillations, the cAMP signaling system that controls aggregation is also capable of excitable behavior, which consists in the transient amplification of suprathreshold pulses of extracellular cAMP. Since the first theoretical model for slime mold aggregation proposed by Keller and Segel in 1970, many theoretical studies have addressed various aspects of the mechanism and function of cAMP signaling in Dictyostelium. This paper presents a brief overview of these developments as well as some reminiscences of the author's collaboration with Lee Segel in modeling the dynamics of cAMP relay and oscillations. Considered in turn are models for cAMP signaling in Dictyostelium, the developmental path followed by the cAMP signaling system after starvation, the frequency encoding of cAMP signals, and the origin of concentric or spiral waves of cAMP.

Animals↗
PubMed2000

Conceptual issues in trichotillomania, a prototypical impulse control disorder.

Impulse control disorders (ICDs) are characterized by irresistible urges to perform acts that result in a reduction of tension and possibly gratification, but also have negative consequences. Trichotillomania, an ICD, is characterized by a recurrent failure to resist impulses to pull out one's hair, resulting in noticeable hair loss. Limited information is available about structural and neurochemical differences in individuals with trichotillomania. Cognitive behavioral techniques are promising treatments for trichotillomania. Pharmacologic treatments have focussed on clomipramine and venlafaxine as potentially effective for the short term control of symptoms in trichotillomania. Selective serotonin reuptake inhibitors, though promising in open trials, seem to be largely ineffective in reducing hair pulling in controlled studies. Durability of pharmacologic benefit for the symptoms of trichotillomania, both in a small trial and in clinical experience, appears to be poor.

Adult↗
PubMed1993

Controlled trials with beta blockers in heart failure: metoprolol as the prototype.

Early studies of acute beta-blocking drug therapy, such as metoprolol and acebutolol, in patients with idiopathic dilated cardiomyopathy (IDC) and survivors of acute myocardial infarction were interpreted to have detrimental or, at best, neutral effects on cardiac and clinical hemodynamics. Subsequent trials of longer duration with metoprolol versus placebo in patients with IDC demonstrated an "exceptional response" to beta-blocker therapy in some individuals. Hemodynamics and patient demographic characteristics appear not to predict those patients who may or may not benefit. Controlled trials with newer beta-adrenoceptor modulating drugs--such as xamoterol, bucindolol, and carvedilol--have been equivocal in some situations. Xamoterol has been associated with progressive heart failure and increased sudden cardiac deaths, whereas bucindolol improved clinical heart failure symptoms and testing hemodynamic parameters, as did treatment with carvedilol, in patients with ischemic cardiomyopathy. The success of these agents in patients with congestive heart failure may be in their ability to modulate the excessive myocardial stimulation of the beta-adrenergic nervous system while benefitting the dynamics of the peripheral system.

Adrenergic beta-Antagonists↗