bluuebunny/crossref_metadata_2025 huggingface dataset:
What Interventions Should Pharmacists Employ to Impact Health Practitioners’ Prescribing Practices?
Authors: Grindrod Kelly A , Patel Payal , Martin Janet E
Published: August 2006

Objective:

To determine which interventions are effective in influencing health practitioners’ prescribing practices and explore differences in intervention complexity, setting, sustainability, cost effectiveness, and impact on patient outcomes.

Methods:

A systematic search for English-language systematic reviews was performed in MEDLINE, Cumulative Index of Nursing and Allied Health Literature, EMBASE, and the Cochrane Library from the date of inception to July 2005 using search terms in accordance with Cochrane recommendations. Included reviews were required to clearly report a search strategy, inclusion/exclusion criteria, literature assessment criteria, and methods for synthesizing or summarizing information and references. Two reviewers independently identified studies for inclusion, assessed study quality, and extracted relevant information. Interventions were classified as consistently effective, inconsistently effective, and effectiveness uncertain.

Results:

Thirty-four of 4585 titles reviewed met the inclusion criteria. Quality scores ranged from 70% to 100%. Consistently effective interventions included reminders (manual and computerized), audit and feedback, educational outreach visits, organizational strategies, and patient-mediated interventions. Inconsistently effective interventions included computer decision support systems and educational meetings. Multi-faceted interventions were consistently shown to be more efficacious than single interventions. Limited data precluded exploration of the effects of interventions in different settings, sustainability of effect, cost effectiveness, and patient clinical outcomes.

Conclusions:

Interventions that are most effective for impacting prescribing practice include audit and feedback, reminders, educational outreach visits, and patient-mediated interventions. To maximize impact, pharmacists’ efforts to positively impact prescribing practices should focus on these intervention types rather than relying primarily on passive didactics or dissemination of guidelines.
Hypotension Following Treatment with Aerosolized Colistin in a Patient with Multidrug-Resistant Pseudomonas aeruginosa
Authors: Hakeam Hakeam A , Almohaizeie Abdullah M
Published: August 2006

Objective:

To report a case of a man who developed temporary hypotension after aerosolized colistin administration.

Case Summary:

A 62-year-old Arab male was admitted to the intensive care unit for respiratory failure and septic shock. Simultaneous therapy using intravenous and aerosolized colistin was initiated for the management of multidrug-resistant Pseudomonas aeruginosa. A significant but transient drop in blood pressure occurred when aerosolized colistin was introduced. However, when it was stopped, but intravenous administration was continued, no hypotension was observed. Moreover, the combined use of aerosolized amikacin with intravenous colistin did not significantly affect blood pressure.

Discussion:

It is widely accepted that aerosolization allows safe administration of colistin in the absence of significant systemic adverse effects. However, in our patient, hypotension was observed with aerosolized colistin, but not with the systemic formulation. The lack of adverse effects with administration of aerosolized amikacin in this patient demonstrates the safety of the aerosolization technique. Use of the Naranjo scale indicated a probable relationship between hypotension and aerosolized colistin administration.

Conclusions:

This case suggests that hypotension may be induced with administration of aerosolized colistin. Although this effect is rare, clinicians should be aware that hypotension may develop in critically ill patients following aerosolized colistin treatment.
Lichenoid Eruption Associated with the Use of Nebivolol
Authors: Bodmer Michael , Egger Sabin S , Hohenstein Elisabeth , Beltraminelli Helmut , Krähenbühl Stephan
Published: August 2006

Objective:

To report a case of lichenoid drug eruption (LDE) after starting antihypertensive treatment with nebivolol, a cardioselective β-blocker.

Case Summary:

Five weeks after starting treatment with nebivolol, a 62-year-old woman presented with erythematous papules on both extremities and skin lesions spreading over the back. She was not being treated with any other drugs. Because the administration of levocetirizine, topical methylprednisolone, and systemic prednisone was unsuccessful, the treatment was stopped and the lesions were biopsied. The histopathological features of the lesions were consistent with LDE. After withdrawal of nebivolol and subsequent readministration of topical methylprednisolone and systemic prednisone, the skin lesions resolved within 12 days. Assessment of the causality revealed a probable relationship between nebivolol and the lichenoid eruptions.

Discussion:

Although β-blockers can be associated with LDE, as of July 7, 2006, this has not been previously reported with nebivolol. T cells invading the dermis are considered to be responsible for epidermal destruction associated with LDE, as has been described for lichenoid forms of chronic graft versus host disease and idiopathic lichen ruber planus.

Conclusions:

Nebivolol can cause LDE, as has been reported with other β-blockers. The underlying mechanism appears to be T cell–mediated. Cross-reactivity with other β-blockers cannot be excluded; therefore, the risk of recurrent LDE should be weighed carefully against the clinical benefit before switching to another β-blocker.
Anorexia nervosa: Valued and visible. A cognitive‐interpersonal maintenance model and its implications for research and practice
Authors: Schmidt Ulrike , Treasure Janet
Published: August 2006

Anorexia nervosa (AN) is highly valued by people with the disorder. It is also a highly visible disorder, evoking intense emotional responses from others, particularly those closest to the person. A maintenance model of restricting anorexia nervosa, combining intra‐ and interpersonal factors is proposed. Four main maintaining factors (perfectionism/cognitive rigidity, experiential avoidance, pro‐anorectic beliefs, response of close others) are suggested and the evidence supporting these is examined. These factors need to be integrated with what is known about starvation‐related maintenance factors. This model departs from other models of AN in that it does not emphasize the role of weight and shape‐related factors in the maintenance of AN; that is, it is culture‐free. Implications for clinical practice and research are discussed.
Validation of screening measures for assessing mood in stroke patients
Authors: Bennett H. E. , Thomas S. A. , Austen R. , Morris A. M. S. , Lincoln N. B.
Published: August 2006

Purpose. There are few validated measures to assess mood in stroke patients and even fewer suitable for all stroke patients, including those with communication problems. The aim of this study was to compare the Stroke Aphasic Depression Questionnaire Hospital version (SADQ‐H), Signs of Depression Scale (SODS), Visual Analogue Mood Scale (VAMS) and Visual Analogue Self‐esteem Scale (VASES) in screening for mood problems after stroke.

Methods. Fifty healthy older adults and 100 stroke patients in hospital completed the VAMS and VASES. A nurse completed the SADQ‐H and SODS in relation to the stroke patients. A relative/carer completed the SADQ‐H and SODS in relation to the healthy older adults. Those without communication problems also completed the Hospital Anxiety and Depression Scale (HADS).

Results. The internal consistency of the scales was low in healthy older adults. In stroke patients the internal consistency of the SADQ‐H, VAMS, and VASES was high (α=.71–.84) but that of the SODS was low (α=.53). In healthy older adults, correlations between the HADS and the VAMS and VASES were high but low between the HADS and SADQ‐H and SODS. In stroke patients, the HADS depression scale correlated significantly with all the scales (0.35–0.55) but only the SADQ‐H 10, VAMS, and VASES were significantly correlated with the HADS anxiety scale (0.40–0.52). Appropriate cut‐offs were found for the SADQ‐H (17/18), SADQ‐H 10 (5/6), SODS (1/2), and VAMS ‘sad’ item (22/23) in comparison to depression on the HADS. No appropriate cut‐offs were identified in comparison to anxiety on the HADS.

Conclusions. The SADQ‐H, SADQ‐H10 and SODS were all appropriate for screening for possible depression after stroke but not for screening for possible anxiety. The SADQ‐H 10 had greater internal consistency and higher sensitivity and specificity than the SODS and is shorter than the SADQ‐H. It was also significantly correlated with both the anxiety and depression scales of the HADS. The SADQ‐H 10 was therefore recommended as the most appropriate for screening purposes. The VAMS and VASES provided no clear cut‐offs for use in screening but scores were highly correlated with the HADS. They are therefore more suitable for assessing severity of low mood rather than for screening purposes. The cut‐offs identified need further validation in an independent sample of stroke patients, including a higher proportion with low mood.
An Investigation of National Culture's Influence on Relationship and Knowledge Resources in Interorganizational Relationships between Japan and the United States
Authors: Griffith David A. , Myers Matthew B. , Harvey Michael G.
Published: August 2006

The increasing globalization of business has heightened the importance of understanding national cultural influences in interorganizational relationships from both a cross-cultural and an intercultural perspective. The authors use Hofstede's (2001) multidimensional national cultural framework to theorize differences in the relationships between key firm resources. Specifically, they explore relationship resources (i.e., the influence of trust on commitment), knowledge resources (i.e., the influence of information sharing on problem resolution), and their linkage (i.e., the influence of commitment on information sharing) both cross-culturally and interculturally from the perspective of Japanese and U.S. firms. The authors use a sample of Japanese and U.S. firms that report on their primary intra-and intercultural business partners to test the hypotheses. The results indicate that national culture influences relationship resources (i.e., the relationship between trust and commitment) and the linkage of relationship resources to knowledge resources (i.e., the relationship between commitment and information sharing). The authors address implications for both academics and practitioners.
Antismoking Messages for the International Teenage Segment: The Effectiveness of Message Valence and Intensity across Different Cultures
Authors: Reardon James , Miller Chip , Foubert Bram , Vida Irena , Rybina Liza
Published: August 2006

Based on an experiment among more than 2000 students in nine culturally diverse countries, this article investigates how the cultural characteristic of uncertainty avoidance moderates the impact of valence and intensity on the effectiveness of antismoking messages. The results show that adolescents with high uncertainty avoidance respond more favorably to loss-framed advertisements than to benefit-framed advertisements, whereas the opposite holds for those with low uncertainty avoidance.
How Smaller Born-Global Firms Use Networks and Alliances to Overcome Constraints to Rapid Internationalization
Authors: Freeman Susan , Edwards Ron , Schroder Bill
Published: August 2006

The authors identify the following key constraints that smaller born-global firms face: lack of economies of scale, lack of resources (financial and knowledge), and aversion to risk taking. The authors explore how such firms overcome these constraints by using technology to achieve competitive advantage and by networking competencies to develop a range of alliances and collaborative partnerships. Thus, the article focuses on a particular aspect of business-to-business marketing, namely, how small firms achieve rapid growth internationally through alliances with suppliers, distributors, and joint-venture partners and how these relationships change over time to meet the changing needs of the partners.
The Commitment Mix: Dimensions of Commitment in International Trading Relationships in India
Authors: Sharma Neeru , Young Louise , Wilkinson Ian
Published: August 2006

The authors identify five types of relationship commitment in international marketing relationships: value-based, affective, locked-in, obligation, and behavioral commitment. They develop and test scales to measure these dimensions on the basis of a study of India-based firms’ international business relationships. The dimensions are interrelated but distinct and vary according to relationship development, performance, and cultural context. The authors find similar patterns of commitment for better-performing relationships with partners in different regions of the world, but there are differences by region for poorer-performing relationships. The results have implications for developing and sustaining successful international marketing relationships and for further research.
C. elegans as a model system to study the function of the COG complex in animal development
Authors: Kubota Yukihiko , Nishiwaki Kiyoji
Published: August 2006

The conserved oligomeric Golgi (COG) complex is an octameric protein complex associated with the Golgi apparatus and is required for proper sorting and glycosylation of Golgi resident enzymes and secreted proteins. Although COG complex function has been extensively studied at the cellular and subcellular levels, its role in animal development mostly remains unknown. Recently, mutations in the components of the COG complex were found to cause abnormal gonad morphogenesis inCaenorhabditis elegans. InC. elegans, the COG complex acts in the glycosylation of an ADAM (a disintegrin and metalloprotease) family protein, MIG-17, which directs migration of gonadal distal tip cells to lead gonad morphogenesis. This is the first link between the COG complex and the function of an ADAM protease that is directly involved in organ morphogenesis, demonstrating the potential ofC. elegansas a model system to study COG function in animal development.
Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata
Authors: Hamill Pamela , Hudson Derek , Kao Richard Y. , Chow Polly , Raj Meera , Xu Hongyan , Richer Martin J. , Jean François
Published: August 2006

SARS-coronavirus (SARS-CoV) encodes a main protease, 3CLpro, which plays an essential role in the viral life cycle and is currently the prime target for discovering new anti-coronavirus agents. In this article, we report our success in developing a novel red-shifted (RS) fluorescence-based assay for 3CLpro and its application for identifying small-molecule anti-SARS agents from marine organisms. We have synthesised and characterised the first generation of a red-shifted internally quenched fluorogenic substrate (RS-IQFS) for 3CLpro based on resonance energy transfer between the donor and acceptor pair CAL Fluor Red 610 and Black Hole Quencher-1 (K
m and k
cat values of 14 μM and 0.65 min-1). The RS-IQFS primary sequence was selected based on the results of our screening analysis of 3CLpro performed using a series of blue-shifted (BS)-IQFSs corresponding to the 3CLpro-mediated cleavage junctions of the SARS-CoV polyproteins. In contrast to BS-IQFSs, the RS-IQFS was not susceptible to fluorescence interference from coloured samples and allowed for successful screening of marine natural products and identification of a coumarin derivative, esculetin-4-carboxylic acid ethyl ester, a novel 3CLpro inhibitor (IC50=46 μM) and anti-SARS agent (EC50=112 μM; median toxic concentration >800 μM) from the tropical marine sponge Axinella corrugata.
Molecular and functional analysis of new members of the wheat PR4 gene family
Authors: Bertini Laura , Cascone Annunziata , Tucci Marina , D'Amore Rosalinda , Di Berardino Iris , Buonocore Vincenzo , Caporale Carlo , Caruso Carla
Published: August 2006

Five new genes belonging to the pathogenesis-related (PR) 4 family have been cloned and characterised in Triticum aestivum. Two full-length genes, named wPR4e and wPR4f-b, were isolated by library screening, demonstrating the presence of a small intron only in wPR4f-b. Two other PR4 genes (wPR4f-a and wPR4f-c) were isolated by PCR, showing very high sequence identity with wPR4f-b and constituting a new sub-family. Transcription start analysis was performed by RLM-RACE, leading to the isolation of a fifth gene, named wPR4g, that is highly homologous to wPR4e; both encode putative vacuolar PR4 proteins (Wheatwin7 and Wheatwin5, respectively). wPR4e and wPR4f sub-family genes are induced by F. culmorum infection, by chemicals that lead to systemic acquired resistance and by wounding, showing different spatial and temporal induction pathways. In silico analysis of the 5′ untranslated regions of wPR4e and wPR4f-b revealed the presence of several abiotic and biotic stress-responsive elements. wPR4e and wPR4f-b putative promoters were fused to the β-glucuronidase (GUS) reporter gene, and transient and stable expression assays demonstrated that both are able to drive expression of GUS. Characterisation of these new PR4 genes and particularly of their 5′ untranslated regions, as well as the determination of their expression patterns, will contribute to our understanding of the responsiveness of this gene family to various stress conditions and of its role in plant defence.
Activity Bidirectionally Regulates AMPA Receptor mRNA Abundance in Dendrites of Hippocampal Neurons
Authors: Grooms Sonja Y. , Noh Kyung-Min , Regis Roodland , Bassell Gary J. , Bryan Monique K. , Carroll Reed C. , Zukin R. Suzanne
Published: August 2006

Activity-dependent regulation of synaptic AMPA receptor (AMPAR) number is critical to NMDA receptor (NMDAR)-dependent synaptic plasticity. Using quantitative high-resolutionin situhybridization, we show that mRNAs encoding the AMPA-type glutamate receptor subunits (GluRs) 1 and 2 are localized to dendrites of hippocampal neurons and are regulated by paradigms that alter synaptic efficacy. A substantial fraction of synaptic sites contain AMPAR mRNA, consistent with strategic positioning and availability for “on-site” protein synthesis. NMDAR activation depletes dendritic levels of AMPAR mRNAs. The decrease in mRNA occurs via rise in intracellular Ca2+, activation of extracellular signal-regulated kinase/mitogen-activated protein kinase signaling, and transcriptional arrest at the level of the nucleus. The decrease in mRNA is accompanied by a long-lasting reduction in synaptic AMPAR number, consistent with reduced synaptic efficacy. In contrast, group I metabotropic GluR signaling promotes microtubule-based trafficking of existing AMPAR mRNAs from the soma to dendrites. Bidirectional regulation of dendritic mRNA abundance represents a potentially powerful means to effect long-lasting changes in synaptic strength.
Lesions of the Basolateral Amygdala Disrupt Conditioning Based on the Retrieved Representations of Motivationally Significant Events
Authors: Dwyer Dominic M. , Killcross Simon
Published: August 2006

One recent perspective (Blundell et al., 2001; 2003; Killcross and Blundell, 2002; Balleine et al. 2003) on the function of the basolateral region of the amygdala (BLA) suggests that it plays an important role in the representation of the sensory features of motivationally significant events. This predicts that lesions of the BLA will not produce a decrement in performance in conditioning procedures based on the formation of associations between the sensory aspects of neutral events but will interfere with conditioning based on associations between neutral cues and motivationally significant events. This prediction is supported by the evidence that BLA lesions were without effect on a sensory preconditioning procedure (experiment 1A) that used neutral cues but that BLA lesions did significantly impair representation-mediated conditioning (experiment 1B) when the target cues were motivationally significant at the time of training. These results demonstrate that animals with lesions of the BLA can represent the sensory aspects of neutral events but not the sensory aspects of motivationally significant events.
Integration of Visuospatial and Effector Information during Symbolically Cued Limb Movements in Monkey Lateral Intraparietal Area
Authors: Oristaglio Jeff , Schneider David M. , Balan Puiu F. , Gottlieb Jacqueline
Published: August 2006

Natural behavior requires close but flexible coordination between attention, defined as selection for perception, and action. In recent years a distributed network including the lateral intraparietal area (LIP) has been implicated in visuospatial selection for attention and rapid eye movements (saccades), but the relation between the attentional and motor functions of this area remains unclear. Here we tested LIP neurons in a task that involved not an ocular but a manual operant response. Monkeys viewed a display containing one cue and several distractors and reported the orientation of the cue (right- or left-facing) by releasing one of two bars grasped, respectively, with the right or left hand. The movement in this task thus was associated with (cued by), but not directed toward, the visual stimulus. A large majority of neurons responded more when the cue rather than when a distractor was in their receptive field, suggesting that they contribute to the attentional selection of the cue. A fraction of these neurons also was modulated by limb release, thus simultaneously encoding cue location and the active limb. The results suggest that the LIP links behaviorally relevant visual information with motor variables relevant for solving a task in a wide range of circumstances involving goal-directed or symbolically cued movements and eye as well as limb movements. A central function of the LIP may be to coordinate visual and motor selection during a wide variety of behaviors.
Background Synaptic Activity Is Sparse in Neocortex
Authors: Waters Jack , Helmchen Fritjof
Published: August 2006

Neurons are continually exposed to background synaptic activityin vivo. This is thought to influence neural information processing, but background levels of excitation and inhibition remain controversial. Here we show, using whole-cell recordings in anesthetized rats, that spontaneous depolarizations (“Up states”) in neocortical pyramidal neurons are driven by sparse, mostly excitatory synaptic activity (less than five inputs per millisecond; ∼10% inhibitory). The mean synaptic conductance change is small (<10 nS at the soma) and opposed by anomalous rectification, resulting in a net increase in input resistance during Up states. These conditions enhance the effectiveness of each synapse at depolarized potentials. Hence, neocortical networks are relatively quiet at rest, and the effect of synaptic background is weaker than previously thought.
Cerebellar Cortical Molecular Layer Inhibition Is Organized in Parasagittal Zones
Authors: Gao Wangcai , Chen Gang , Reinert Kenneth C. , Ebner Timothy J.
Published: August 2006

Molecular layer inhibitory interneurons generate on-beam and off-beam inhibition in the cerebellar cortex that is hypothesized to control the timing and/or spatial patterning of Purkinje cell discharge. On- and off-beam inhibition has been assumed to be spatially uniform and continuous within a folium. Using flavoprotein autofluorescence optical imaging in the mouse cerebellar cortexin vivo, this study demonstrates that the inhibition evoked by parallel fiber and peripheral stimulation results in parasagittal bands of decreases in fluorescence that correspond to zebrin II-positive bands. The parasagittal bands of decreased fluorescence are abolished by GABAAantagonists and reflect the activity of molecular layer interneurons on their targets. The same banding pattern was observed using Ca2+imaging. The bands produce spatially specific decreases in the responses to peripheral input. Therefore, molecular layer inhibition is compartmentalized into zebrin II parasagittal domains that differentially modulate the spatial pattern of cerebellar cortical activity.
Central and Medial Amygdaloid Brain-Derived Neurotrophic Factor Signaling Plays a Critical Role in Alcohol-Drinking and Anxiety-Like Behaviors
Authors: Pandey Subhash C. , Zhang Huaibo , Roy Adip , Misra Kaushik
Published: August 2006

Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family of neurotrophins and plays a vital role in synaptic plasticity. This study investigated the involvement of the amygdaloid BDNF system in molecular mechanisms underlying anxiety and alcohol-drinking behaviors. Male Sprague Dawley rats were cannulated targeting central amygdala (CeA), medial amygdala (MeA), or basolateral amygdala (BLA), and BDNF expression was manipulated using an antisense oligodeoxynucleotide (ODN) strategy. Anxiety-like and alcohol-drinking behaviors were measured after infusion of BDNF sense and antisense ODNs with or without BDNF coinfusion, using the elevated plus-maze test and two-bottle free-choice paradigm, respectively. Here we report that BDNF antisense ODN infusions into the CeA and MeA, but not BLA, provoked anxiety-like behaviors in rats, which were rescued by BDNF coinfusion. The levels of BDNF, p-ERK1/2 (phosphorylated extracellular signal-regulated kinases 1/2), and p-CREB (phosphorylated cAMP responsive-element binding protein) were decreased by BDNF antisense, but not by sense, ODN infusions, which were restored to normal after BDNF coinfusions. Furthermore, BDNF antisense ODN infusions into the CeA or MeA, but not into BLA, increased alcohol intake, which was attenuated by BDNF coinfusions. These novel results suggest that decreased BDNF levels in the CeA and MeA, but not in the BLA, are crucial in regulating alcohol-drinking and anxiety-like behaviors in rats.
Aedeagus morphology as a discriminant marker in two closely related Cactophilic species of Drosophila (Diptera; Drosophilidae) in South America
Authors: Franco Fernando F. , Prado Pedro R.R. , Sene Fábio M. , Costa Luciano F. , Manfrin Maura H.
Published: August 2006

Drosophila serido and D. antonietae are sibling species belonging to the Drosophila buzzatii cluster. Morphologically, they can only be discriminated by quantitative traits. In this paper we analyze the length and equalized average curvature of four regions of the aedeagus of D. antonietae and D. serido. Specimens of D. serido and D. antonietae were classified correctly 96.74% of the time. Based only on the variable that most contributed to the discrimination of the groups (equalized average curvature of the arch IV of the aedeagus), we observed significant intraspecific morphological divergence in D. serido in relation to the D. antonietae, in agreement with other markers. The high morphological divergence in equalized average curvature of the arch IV of the aedeagus shows that this region evolved faster than others, since the divergence of the two species. The importance of the present study to the understanding of the genetic basis that controls the formation of the aedeagus, in the species of the Drosophila buzzatii cluster, is discussed.
Rhizophores in Rhizophora mangle L: an alternative interpretation of so-called ''aerial roots''
Authors: Menezes Nanuza L. de
Published: August 2006

Rhizophora mangle L., one of the most common mangrove species, has an aerial structure system that gives it stability in permanently swampy soils. In fact, these structures, known as "aerial roots" or "stilt roots", have proven to be peculiar branches with positive geotropism, which form a large number of roots when in contact with swampy soils. These organs have a sympodial branching system, wide pith, slightly thickened cortex, collateral vascular bundles, polyarch stele and endarch protoxylem, as in the stem, and a periderm produced by a phellogen at the apex similar to a root cap. They also have the same type of trichosclereid that occurs in the stem, with negative geotropism, unlike true Rhizophora roots, which do not form trichosclereids at all. On the other hand, these branches do not form leaves and in this respect they are similar to roots. These peculiar branches are rhizophores or special root-bearing branches, analogous to those found in Lepidodendrales and other Carboniferous tree ferns that grew in swampy soils.
Paleoenvironment interpretation of a 1760 years B.P. old sediment in a mangrove area of the Bay of Guanabara, using pollen analysis
Authors: Barth Ortrud M. , São-Thiago Luiz E.U. , Barros Marcia A.
Published: August 2006

A sediment sample was obtained at 122 cm from the top of a drilling core in the Guapimirim mangrove, Bay of Guanabara, and analyzed using pollen analysis. This muddy core reached a sandy ground at 133 cm. 14C datation got the age of 1760 ± 50 years B.P. The most frequent pollen grains were mangrove species of Rhizophora mangle, Laguncularia racemosa and Avicennia schaueriana. "Restinga" and tropical rain forest vegetation was recognized behind the mangrove. After the last sea transgression at 2500 years B.P., the water level lowered to its actual size, allowing the installation of this mangrove.
The structural molecular biology network of the State of São Paulo, Brazil
Authors: Barbosa João A.R.G. , Netto Luis E.S. , Farah Chuck S. , Schenkman Sergio , Meneghini Rogério
Published: August 2006

This article describes the achievements of the Structural Molecular Biology Network (SMolBNet), a collaborative program of structural molecular biology, centered in the State of São Paulo, Brazil, and supported by São Paulo State Funding Agency (FAPESP). It gathers twenty scientific groups and is coordinated by the scientific staff of the Center of Structural Molecular Biology, at the National Laboratory of Synchrotron Light (LNLS), in Campinas. The SMolBNet program has been aimed at 1) solving the structure of proteins of interest related to the research projects of the groups. In some cases, the choice has been to select proteins of unknown function or of possible novel structure obtained from the sequenced genomes of the FAPESP genomic program; 2) providing the groups with training in all the steps of the protein structure determination: gene cloning, protein expression, protein purification, protein crystallization and structure determination. Having begun in 2001, the program has been successful in both aims. Here, four groups reveal their participation in the program and describe the structural aspects of the proteins they have selected to study.
Aspectos moleculares do câncer tiroideano
Authors: Barril Nilce , Tajara Eloiza H.
Published: August 2006

A proliferação da célula tiroideana normal é regulada por fatores de crescimento estimuladores e inibidores, que atuam através de seus receptores de membrana e, subseqüentemente, através de transdutores citoplasmáticos. Na glândula normal adulta, o equilíbrio de sinais é tal que a proliferação é mínima, enquanto nas neoplasias o crescimento resulta de um distúrbio irreversível desse equilíbrio. Apesar do número de moléculas envolvidas nesse processo ser grande, apenas um pequeno subgrupo parece estar envolvido na tumorigênese tiroideana. Tais proteínas são codificadas pelos genes RAS, RET, NTRK1 e TP53. O transdutor de sinais ras é ativado por mutações em ponto e constitui uma alteração genética precoce nos tumores com histologia folicular. Os genes dos receptores de crescimento RET e NTRK1 são alterados por rearranjos cromossômicos do tipo translocação ou inversão nos carcinomas papilares e por mutações em ponto nos medulares. As alterações do gene TP53, por sua vez, têm sido observadas em carcinomas tiroideanos pobremente diferenciados e na maioria dos indiferenciados, o que sugere sua participação na progressão dessas lesões. O modelo molecular da carcinogênese tiroideana, embora ainda incompleto, pode fornecer instrumentos importantes para o diagnóstico diferencial e para o desenvolvimento de novas técnicas terapêuticas nesse grupo de neoplasias.
Crescimento de crianças diabéticas em controle ambulatorial em hospital universitário
Authors: Cunh Edna F. , Silva Jr. Gildásio R. , Clemente Eliete L.S. , Gomes Marília B.
Published: August 2006

Com o objetivo de estudar o crescimento de pacientes com diabetes mellitus tipo 1 (DM1) acompanhados no Ambulatório da Disciplina de Diabetes do Hospital Universitário Pedro Ernesto - UERJ, foram avaliados, em corte transversal, 34 crianças e adolescentes com média (±DP) de 12±3,7 anos de idade, sendo 19 do sexo masculino. A idade de início do DM1 era de 7,8±4,1 anos e a duração da doença 4,2±3,1 anos. A mediana (variação) da relação altura para idade representada por unidades de desvio-padrão, escore Z, (Z A/I), foi de -0,05 (-1,8 a 1,1). Apenas 8,8% e 20,6% do grupo tiveram Z A/I menores que -1,5 e -1, respectivamente. O Z A/I mostrou-se significativamente diferente entre os subgrupos de £5 anos (SG1) e de >5 anos de doença (SG2), sendo, respectivamente: 0,26 (-1,47 a 1,10) e -0,77 (-1,88 a 0,73); p=0,03. SG1 e SG2 diferem também na idade de início do DM1 que é maior nos pacientes do SG1, respectivamente: 9,2±3,9 anos e 5,2±3,3 anos; p=0,01 Houve correlação negativa do Z A/I com o tempo de doença no grupo geral (r=-0,47; p<0,01). Quando o grupo foi subdividido por índice de hemoglobina glicada (hemoglobina glicada / máximo valor da normalidade) em controle adequado (<1,33) e não adequado ( > ou = 1,33), observamos diferença do Z A/I entre grupos, respectivamente: 0,29 (-1,69 a 0,85) e -0,43 (-1,88 a 1,10); p=0,02. A mediana do escore Z para peso em relação à idade (Z P/I) foi de 0,04 (-1,64 a 1,53). Apenas dois pacientes tiveram seus índices de massa corporal no percentil 85. Em conclusão, os escores de desvio padrão de altura para idade dos pacientes em controle ambulatorial, com tratamento convencional, mostraram correlação com o tempo de doença, sendo mais comprometidos nos pacientes com maior tempo de doença e controle glicêmico não adequado.
Evolução da displasia fibrosa óssea na síndrome de McCune Albright
Authors: Farhat Helena L. , Silva Magnus Régios D. da , Lazaretti-Castro Marise , Verreschi Ieda T. N.
Published: August 2006

A tríade clássica da Síndrome de McCune Albright (SMA) - displasia fibrosa poliostótica (DFP), máculas cutâneas "café au lait" e hiper-função autônoma de uma ou mais glândulas endócrinas - envolve mutações ativadoras do gene GNAS1, codificador da proteína Galfas e conseqüente aumento da produção do sinalizador intracelular AMPc em diferentes tecidos. Embora a pseudo-puberdade precoce (PPP) seja a manifestação clínica mais freqüente, são as alterações ósseas que conferem a maior morbidade à síndrome. Apresentamos o seguimento clínico endocrinológico e a evolução da doença óssea em 4 pacientes portadores da SMA, das quais 3 delas estão sendo tratadas com bisfosfonato (Pamidronato, 2mg/kg). Três das 4 pacientes apresentaram pseudo-puberdade precoce e duas delas desenvolveram hipertiroidismo. A variação do nível de fosfatase alcalina (FA) foi o indicador bioquímico da doença óssea, cujas complicações foram dor e fratura além de obstrução do canal lacrimal em uma e amaurose unilateral em outra como conseqüência das deformidades crânio-faciais. A infusão de pamidronato endovenoso produziu melhora das dores ósseas e reduziu (37% - 54%) os níveis de FA em todas as pacientes. Entretanto, a melhora da qualidade do osso com o uso do bisfosfonato ainda é incerta e para a qual necessitamos de estudos randomizados e com longo prazo de observação.
Análise clínica e evolução de 70 casos de lesões podais infectadas em pacientes diabéticos
Authors: Jorge Beatriz H. , Borges Maria de Fátima , Brito Vinícius N. de , Santos Thessa G.M. dos , Thirone Ana Cláudia P.
Published: August 2006

O presente trabalho tem como objetivo analisar 70 pacientes diabéticos portadores de lesões podais infectadas, internados para tratamento no Hospital Escola da Faculdade Federal de Medicina do Triângulo Mineiro no período compreendido entre 1989 e 1998. As lesões foram analisadas considerando-se o tipo de diabetes mellitus (DM) apresentado pelo paciente, tempo decorrido entre o diagnóstico de DM e a internação, agentes etiológicos mais freqüentemente encontrados nas culturas das secreções, tipo de tratamento requerido e evolução clínica dos pacientes. A maioria dos pacientes estudados (87%) era portadora de DM tipo 2. Não se observou diferença estatística quanto ao sexo, com predomínio nas 6ª e 7ª décadas de vida. As lesões foram mais freqüentes nos pacientes com mais de 5 anos de diagnóstico de DM. As bactérias mais comumente encontradas nas culturas das secreções foram Proteus mirabilis e Staphylococcus sp. Os pacientes receberam terapia antibiótica específica, curativos diários e desbridamentos, quando necessários. Sessenta e um por cento dos pacientes requererem amputação e 15,7% foram a óbito por septicemia. As internações foram prolongadas, com duração média de 38 dias. As lesões podais em pacientes diabéticos são um grande problema de saúde pública. O tratamento é prolongado, podendo trazer mudanças drásticas na qualidade de vida dos pacientes. A prevenção ainda é a melhor maneira de combatermos este problema.
Considerações sobre os marcadores bioquímicos do metabolismo ósseo e sua utilidade prática
Authors: Vieira José Gilberto H
Published: August 2006

O uso de marcadores bioquímicos do metabolismo ósseo na prática clínica tem se expandido de maneira considerável. Isto se deve ao surgimento de novos métodos e de um melhor conhecimento sobre a fisiopatologia das doenças ósteo-metabólicas, em especial a osteoporose. Os marcadores podem ser divididos em marcadores de formação, que refletem a atividade dos osteoblastos, e os de reabsorção, que refletem a atividade dos osteoclastos. Dentre os primeiros destacam-se a fosfatase alcalina óssea e a osteocalcina, e dentre os últimos os fragmentos derivados da reabsorção do colágeno, como as piridino-linas e os telopeptídeos carboxi e amino terminais. Além das aplicações já consagradas, como o diagnóstico e acompanhamento de patologias com importantes repercussões ósseas como a doença de Paget, o hiperparatiroidismo primário e outras, novas aplicações têm sido estudadas. Dentre estas, a que mais parece fundamentada é o acompanhamento do efeito de terapêutica específica no tratamento da osteoporose; a curto prazo, 1 a 3 meses, é possível a verificação da eficácia terapêutica, fato só possível com densitometria óssea após 1 a 2 anos. Novos métodos, em especial para a medida de marcadores de reabsorção no soro, devem tornar ainda mais abrangente a aplicação destes ensaios.
Diagnóstico por imagem na osteoporose
Authors: Meirelles Eduardo de Souza
Published: August 2006

Nesta revisão, o autor inicialmente enumera, por ordem cronológica de introdução na prática clínica médica, os diversos métodos de imagem utilizados no diagnóstico e seguimento da osteoporose. Compara a precisão, acurácia, duração, segurança (dose de radiação), indicações, sensibilidade e especificidade dos diversos métodos de imagem descritos, com destaque para a radiografia simples, a densitometria óssea e a ultra-sonometria óssea. Faz discussão das vantagens e desvantagens da densitometria óssea em comparação à ultra-sonometria óssea, ponderando que, apesar do recente grande desenvolvimento da ultra-sonometria óssea, a densitometria óssea pela técnica de raios-X de dupla energia (DEXA), continua sendo considerada a técnica padrão-ouro no diagnóstico e seguimento da osteoporose. Conclui pela necessidade de técnicas de imagem com medidas tridimensionais de volume, ao invés das atuais medidas bidimensionais de área, de padronização nacional ou regional de um banco de dados de referência composto por indivíduos controles normais brasileiros e por fim, de padronização mundial da tecnologia e conseqüentes medidas empregadas pelos diferentes fabricantes de equipamentos de densitometria e ultra-sonometria óssea.
Hipocalcemia
Authors: Arioli Edson L. , Corrêa Pedro Henrique S.
Published: August 2006

A hipocalcemia está sendo diagnosticada mais freqüentemente pelos clínicos, e a conduta depende do conhecimento da sua fisiopatologia. A manutenção da calcemia dentro da normalidade é o resultado da interação do PTH e da vitamina D sobre o osso, rim e o intestino. O receptor de sensor de cálcio deve ser incluído na sua análise. O diagnóstico é realizado pela dosagem de cálcio, ou melhor, do cálcio ionizado. O diagnóstico diferencial entre várias causas de hipocalcemia pode ser realizado, permitindo um tratamento direcionado. Nesta revisão, veremos os mecanismos responsáveis no diagnóstico diferencial e a terapêutica apropriada.
O controle hipotalâmico da fome e da termogênese: implicações no desenvolvimento da obesidade
Authors: Velloso Lício A.
Published: August 2006

O aumento da prevalência de obesidade em várias regiões do planeta vem se revelando como um dos mais importantes fenômenos clínico-epidemiológicos da atualidade. Fatores como a mudança do hábito alimentar e o estilo de vida sedentário, aliados a determinantes genéticos ainda pouco conhecidos, desempenham um papel relevante na patogênese desta doença. Nos últimos dez anos, desde o descobrimento do hormônio leptina, avanços consideráveis foram obtidos na caracterização dos mecanismos hipotalâmicos do controle da ingestão alimentar e da termogênese. Tais avanços têm revelado as particularidades de um sistema complexo e integrado, e têm oferecido novas perspectivas para abordagens terapêuticas farmacológicas específicas. Esta revisão apresenta os mais recentes avanços nesta área, tendo como foco a ação hipotalâmica da leptina e da insulina e explorando a hipótese de que a resistência à ação central destes hormônios possa ser o elo entre a obesidade e as outras condições clínicas nas quais a resistência à insulina desempenha um papel patogenético proeminente.
Modelos experimentais de resistência à insulina e obesidade: lições aprendidas
Authors: Cesaretti Mario Luís Ribeiro , Kohlmann Junior Osvaldo
Published: August 2006

Para melhor compreender o papel de cada um dos elementos envolvidos na fisiopatologia da obesidade e da resistência à insulina, pesquisadores utilizam-se de modelos experimentais, que podem determinar de maneira controlada o papel de cada um dos componentes da resistência à insulina e obesidade e, desta maneira, fornecer subsídios para a melhor compreensão da fisiopatolologia e tratamento da resistência à insulina e obesidade. A obesidade e a resistência à insulina experimentais podem ser verificadas quando ocorre diminuição da resposta à leptina, seja por menor produção ou alteração no seu receptor, modificações no receptor de insulina, por deleção do receptor ou alteração da transdução dos seu sinal, exacerbação do efeito de peptídeos orexígenos e/ou menor ação de peptídeos anorexígenos no hipotálamo, ou ainda secundária à hipertensão arterial, como nos ratos espontaneamente hipertensos. O excesso de glicocorticóides, a adição de uma dieta rica em frutose, ou ainda uma dieta hipercalórica, além da lesão hipotalâmica induzida pela administração neonatal de monoglutamato de sódio, são exemplos de obesidade e resistência à insulina induzidos.
Gordura visceral e síndrome metabólica: mais que uma simples associação
Authors: Ribeiro Filho Fernando F. , Mariosa Lydia S. , Ferreira Sandra R. G. , Zanella Maria Teresa
Published: August 2006

A síndrome metabólica (SM) é vista atualmente como uma epidemia mundial, com números alarmantes, associada a alta morbi-mortalidade cardiovascular e elevado custo sócio-econômico. O ganho ponderal é preditor independente para o desenvolvimento da SM, embora nem todos os indivíduos obesos a apresentem. Por outro lado, certas populações com baixa prevalência de obesidade apresentam elevada prevalência da SM e mortalidade cardiovascular. A distribuição da gordura corporal é relevante, e especificamente a gordura visceral (GV) parece ser o elo entre o tecido adiposo e a resistência à insulina (RI), característica da SM. Na última década, o tecido adiposo deixou de ser um simples reservatório de energia para se transformar num complexo órgão com múltiplas funções. A GV apresenta características metabólicas diferentes da gordura subcutânea glúteo-femoral, as quais favorecem a instalação do quadro de RI. Diversos estudos revelam a estreita relação da adiposidade abdominal com a tolerância à glicose, hiperinsulinemia, hipertrigliceridemia e hipertensão arterial. Mais que uma simples associação, recentemente, acredita-se que a GV desempenha um papel central na fisiopatologia da SM. Assim, a quantificação da GV se torna importante para identificar indivíduos com maior risco para o desenvolvimento da SM, eleitos para sofrer intervenções precoces na tentativa de reduzir o impacto das anormalidades metabólicas sobre a mortalidade cardiovascular. Este artigo discute particularidades da distribuição central de gordura, no contexto da SM, possíveis mecanismos fisiopatogênicos relacionados à GV e os métodos disponíveis para a avaliação da adiposidade abdominal.
Glitazonas e síndrome metabólica: mecanismos de ação, fisiopatologia e indicações terapêuticas
Authors: Gomes Marília de Brito
Published: August 2006

O diabetes mellitus (DM) é considerado um problema de saúde pública em países devido às suas complicações crônicas macro e microvasculares, com grande impacto na morbimortalidade dos pacientes. A doença é o estágio final de uma síndrome crônica e progressiva, cujas anormalidades fisiopatológicas iniciam-se anos antes do diagnóstico clínico da doença. A síndrome metabólica (SM) é conseqüente ao aumento mundial da prevalência de obesidade. O DM é freqüentemente associado com condições clínicas e laboratoriais que fazem parte da SM, como a obesidade, hipertensão arterial, dislipidemia e microalbuminúria, também fatores de risco cardiovascular. Estudos populacionais demonstram aumento na prevalência de todos os fatores que compõem esta síndrome do pré-diabetes ao DM manifesto, resultando em elevada prevalência de doença cardiovascular e morbimortalidade. Estima-se que >80% dos pacientes com DM apresentem SM. As glitazonas são agonistas PPAR-gama que melhoram a sensibilidade insulínica. Estas drogas induzem à transcrição de genes relacionados ao metabolismo glicídico e lipídico e à expressão de proteínas inflamatórias e endoteliais associadas com o processo aterosclerótico, resultando em melhora da função endotelial. Entretanto, algumas questões relacionadas às glitazonas merecem mais estudos, como a causa de seus efeitos colaterais (ganho de peso, edema e desenvolvimento de insuficiência cardíaca congestiva).
O endotélio na síndrome metabólica
Authors: Bahia Luciana , Aguiar Luiz G. K. de , Villela Nivaldo Ribeiro , Bottino Daniel , Bouskela Eliete
Published: August 2006

O endotélio é responsável pela manutenção da homeostase vascular. Em condições fisiológicas, mantém o tônus vascular, o fluxo sangüíneo laminar, a fluidez da membrana plasmática, o equilíbrio entre coagulação e fibrinólise, a inibição da proliferação e da migração celulares e o controle da resposta inflamatória. A disfunção endotelial é definida como uma alteração do relaxamento vascular por diminuição da biodisponibilidade de fatores de relaxamento derivados do endotélio, principalmente o óxido nítrico (NO). Estas respostas vasomotoras anormais ocorrem na presença de inúmeros fatores de risco para a aterosclerose. A síndrome metabólica é considerada um estado de inflamação crônica que se acompanha de disfunção endotelial e ocasiona aumento na incidência de eventos isquêmicos cardiovasculares e elevada mortalidade. Essa revisão abordará o processo fisiológico de regulação da função vascular pelo endotélio, os métodos disponíveis para avaliação in vivo da disfunção endotelial e as terapias capazes de melhorar a função vascular e conseqüentemente minimizar o risco cardiovascular dessa síndrome tão prevalente no nosso meio.