bluuebunny/crossref_metadata_2025 huggingface dataset:
Calatytic Mechanism and Activity of Bis(2,2′ : 6′,2″-terpyridine) rhodium(III) for the Reduction of NAD+ into NADH in a Photosensitized Reaction System
Authors: Umeda Keisuke , Nakamura Asao , Toda Fujio
Published: August 2006

Rh(terpy)23+ was used as a reduction catalyst for NAD+ into NADH in a photosensitized reaction system containing Ru(bpy)32+ (as a photosensitizer) and TEOA (triethanolamine) (as an electron donor). At pH 7.7, an effective NADH-formation (1.04 mM (1 M = 1 mol dm−3)) was observed after 90 min of light-irradiation, whereas a low yield of NADH at pH 6.5 or pH 10.0 (0.1 and 0.21 mM respectively) was obtained after 90 min of irradiation. Although the electron donor activity of TEOA is likely to be dependent on the pH conditions, the photosensitized reaction in the TEOA–Ru(bpy)32+–Rh(terpy)23+ system showed little pH influence in that growth in the absorbance at 440 nm, since the reduction of Rh(terpy)23+ at pH 7.7 is ca. 1.5-fold as large as at pH 6.3. The main reason for the NADH-formation dependence on the pH was found to be caused by the dependence of the catalytic activity of the reduced form of Rh(terpy)23+ on the pH conditions. In addition, the IR spectrum of Rh(terpy)23+ reduced at pH 8.0 shows a peak due to rhodium-hydride stretching (2100 cm−1), whereas that Rh(terpy)23+ reduced at pH 10.0 and/or pH 6.5 shows no peak in that region of wavenumbers. These results indicate that the reduction of NAD+ into NADH in the photosensitized reaction system is catalyzed by Rh(terpy)23+ according to hydride-transfer route.
Synthesis of Cyclopent[a]azulenes and 1(3)-Methylenecyclopent[a]azulene Derivatives Having an Electron Withdrawing Group at the 9-Position
Authors: Yasunami Masafumi , Hioki Takanori , Kitamori Yoichiro , Kikuchi Ikue , Takase Kahei
Published: August 2006

1H- and 3H-Cyclopent[a]azulenes having an electron withdrawing group, such as a methoxycarbonyl or a cyano group, at the 9-position were synthesized from their dihydro compounds by means of bromination with NBS and succeeding dehydrobromination by refluxing in chloroform. Base-catalyzed condensation of these cyclopent[a]azulenes with carbonyl compounds afforded 1-methylene-1H- and 3-methylene-3H-cyclopent[a]azulene derivatives having an electron withdrawing group at the 9-position. The physical properties of these methylenecyclopent[a]azulenes are also discussed.
Efficient Preparation of (Z)-2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-[(fluoromethoxy)imino]acetic Acid
Authors: Kanai Takeo , Kai Yasunobu , Sato Nobuaki , Naito Toshihiko , Kamiya Takashi , Nakamura Takaharu , Ogura Katsuyuki
Published: August 2006

(Z)-2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-[(fluoromethoxy)imino]acetic acid (2), a useful chemical modifier of cephalosporin antibiotics, was efficiently synthesized from 2-[(fluoromethoxy)imino]-1,3-propanedinitrile. The stereochemical structure of 2 was unambiguously determined by X-ray crystallography.
Synergistic Effects of 2,2′-Bipyridyl and Potassium Hexacyanoferrate(II) on Electroless Copper Plating from Triethanolamine Bath
Authors: Kondo Koji , Kojima Katsuaki , Ishida Nobumasa , Irie Masahiro
Published: August 2006

The synergistic effects of 2,2′-bipyridyl and potassium hexacyanoferrate(II) on the plating rate and the deposit quality were examined in the triethanolamine (TEA) electroless copper bath. The simultaneous addition of 2,2′-bipyridyl and potassium hexacyanoferrate(II) enhanced not only the plating rate but also the foil quality. The elongation of the foil produced in the TEA bath containing these two additives was 10 times larger than that produced in the bath containing only 2,2′-bipyridyl. The analysis based on the adsorption model revealed that the simultaneous addition of 2,2′-bipyridyl and potassium hexacyanoferrate(II) increases the respective adsorption equilibrium constants. From the analysis, the synergistic effects was attributed to the adsorption of 2,2′-bipyridyl and potassium hexacyanoferrate(II) on the surface with mutual interactions.
A Soap Bubble Model for Coalescence, Rearrangement, and Splitting Reactions of Fullerenes
Authors: Ohmae Takayuki
Published: August 2006

Coalescence, rearrangement, and splitting reactions of fullerenes are examined by use of a soap bubble model, where fullerenes are replaced by soap bubbles of a perfectly elastic body, to yield the predictions of the modes of these processes.
Formation of Uniform Lanthanum(III) Carbonate Hydroxide Particles in the Presence of 1,2-Ethanediamine and Their Conversion into Oxides
Authors: Hamada Shuichi , Kudo Yoshiyuki , Matsuda Hiroaki
Published: August 2006

Uniform spherical particles of crystalline lanthanum(III) carbonate hydroxide were prepared by aging at 100 °C the corresponding 1,2-ethanediamine complex solution in the presence of carbonate ion under specified conditions. The latter anions were generated from a mild oxidation of the ligand with nitrate ions present. The carbonate hydroxide particles were completely converted into the oxides at 900 °C without deformation.
Molecular Electrostatic Potential Map Analysis of Metal Cation Interaction with Nucleophilic Molecules
Authors: Kikuchi Osamu , Yamaguchi Kaoru , Morihashi Kenji , Yokoyama Yukihiro , Nakayama Mitsunobu
Published: August 2006

The interactions between metal cations, Li+, Na+, K+, Be2+, Mg2+, Ca2+, and Al3+ and nuleophilic molecules, NH3, H2O, HF, PH3, H2S, and HCl were calculated by the ab initio method with the MIDI-4 basis set and were analyzed on the basis of the molecular electrostatic potential (MEP) maps of the nucleophilic molecules. The position where each cation is expected to be trapped by the nucleophilic molecule can fairly be estimated as the distance from the MEP minimum point using the ionic radius of the cation, irrespective of the nucleophiles and cations.
Hyponatremia Associated with Selective Serotonin-Reuptake Inhibitors in Older Adults
Authors: Jacob Susan , Spinier Sarah A
Published: August 2006

Objective:

To review the incidence, risk factors, mechanism, times of onset and resolution, and treatment of hyponatremia associated with selective serotonin-reuptake inhibitors (SSRIs).

Data Sources:

An English-language literature search was conducted using MEDLINE (1966–December 2005) using the search terms selective serotonin-reuptake inhibitor, hyponatremia, syndrome of inappropriate secretion of antidiuretic hormone, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. Additional references were identified by reviewing bibliographies of articles retrieved.

Study Selection and Data Extraction:

Relevant data were extracted from published reports, letters, and studies of humans with hyponatremia and/or syndrome of inappropriate secretion of antidiuretic hormone (SIADH) secondary to SSRIs. All articles identified from data sources were reviewed for relevant information. Applicable information was included in this review.

Data Synthesis:

Numerous case reports, observational studies, and case-controlled studies, as well as one prospective clinical trial, have reported hyponatremia associated with SSRI use, with the incidence varying from 0.5% to 32%. Risk factors for the development of hyponatremia with SSRIs include older age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium concentration. In published reports, hyponatremia developed within the first few weeks of treatment and resolved within 2 weeks after therapy was discontinued. The mechanism by which SSRIs cause hyponatremia is thought to be secondary to development of SIADH. Treatment of isovolemia hypotonic hyponatremia associated with SSRI use includes water restriction and mild diuresis with a loop diuretic. More severe cases may be treated with higher doses of loop diuretics and hypertonic saline. There have been few reports of rechallenge with the same or another SSRI or substitution of another agent from a different therapeutic class. In some, but not all, cases hyponatremia recurred.

Conclusions:

Practitioners should be on the alert for this potentially life-threatening adverse event, especially in older adults with other risk factors for developing hyponatremia.
Drug Therapy Recommendations from the 2005 ACC/AHA Guidelines for Treatment of Chronic Heart Failure
Authors: Howard Patricia A , Cheng Judy WM , Crouch Michael A , Colucci Vincent J , Kalus James S , Spinier Sarah A , Munger Mark
Published: August 2006

Objective:

To review and discuss key aspects of the drug therapy recommendations in the American College of Cardiology (ACC)/American Heart Association (AHA) 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure (HF) in the Adult.

Data Sources:

Data were obtained from the ACC/AHA 2005 Guideline Update for Chronic HF. English-language clinical trials, observational studies, and pertinent review articles evaluating the pharmacotherapy of chronic HF were identified, based on MEDLINE searches through January 2006.

Study Selection:

Articles presenting information that impacts the evidence base for recommendations regarding the use of various drug therapies in patients with chronic HF were evaluated.

Data Synthesis:

The ACC/AHA 2005 Guideline Update for HF provides revised, evidence-based recommendations for the treatment of chronic HF. The new guidelines are based on a staging system that recognizes both the development and progression of HF. Recommendations are provided for 2 stages of patients (A and B) who do not yet have clinical HF but are clearly at risk and 2 stages (C and D) that include patients with symptomatic HF. The guidelines continue to emphasize the important role of neurohormonal blockade with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-adrenergic blockers, and aldosterone antagonists. Based on recent trials, updated recommendations address the roles of combination therapy and the selective addition of hydralazine and isosorbide dinitrate. Along with specific drug recommendations, information on the practical use of various drugs is provided. Although the guidelines primarily focus on HF due to systolic dysfunction, general recommendations are also provided for patients with preserved systolic function.

Conclusions:

The ACC/AHA 2005 Guideline Update provides evidence-based recommendations for healthcare professionals involved in the care of adults with chronic HF. Recent clinical trial findings have further clarified the evolving role of neurohormonal-blocking drugs in the prevention and treatment of HF.
Obsessive‐compulsive beliefs and magical ideation in eating disorders
Authors: Lavender Anna , Shubert Iljana , de Silva Padmal , Treasure Janet
Published: August 2006

Objectives. Similarities in patterns of cognition and behaviour between patients with eating disorders and those with obsessive‐compulsive disorder (OCD) have long been recognized, and comorbidity between these disorders has been shown to be high. However, there has been little investigation of the cognitive content shared between eating disorders and OCD. It has been suggested that a cognitive analysis of the overlap between the disorders may help to increase understanding of each, and have potentially useful clinical implications. The present study aimed to investigate the presence of obsessive‐compulsive beliefs and magical ideation (MI) in a group of eating‐disordered participants.

Method. One hundred seventy‐seven volunteers with a history of or current eating disorder completed the Obsessive Beliefs Questionnaire (OBQ), the Interpretation of Intrusions Inventory (III) and the Magical ideation scale (MIS).

Results. Eating‐disordered participants demonstrated levels of the beliefs measured comparable to or higher than those with OCD.

Conclusions. The results supported the hypothesis that the belief domains investigated are relevant to eating‐disordered individuals. This has interesting theoretical and clinical implications. Further research will be required to elucidate the role of these types of cognitions in the relationship between eating disorders and OCD, and to clarify their role in the psychopathology of eating disorders.
Regression equations for predicting scores of persons over 65 on the Rey Auditory Verbal Learning Test, the mini‐mental state examination, the trail making test and semantic fluency measures
Authors: Knight Robert G. , McMahon Jennifer , Green Timothy J. , Skeaff C. Murray
Published: August 2006

Objectives.Scores on neuropsychological tests are often used to detect abnormal changes in cognition in older persons. Accordingly, it is important to have normative data that allow the abnormality of a test score to be determined precisely and accurately. Regression equations that estimate an expected score based on demographic or premorbid factors can be an efficient method of making normative comparisons. Our aim was to compute regression equations with age, gender and estimated premorbid IQ as predictors of scores on the Rey Auditory Verbal Learning Test (AVLT), the Trail Making Test (TMT), Mini‐mental State Examination (MMSE) and measures of semantic fluency.

Design.All measures were administered to a group of 272 healthy older persons aged between 65 and 90 during the pre‐treatment phase of a study evaluating the effect of nutritional supplements on cognition. Premorbid IQ was estimated using the National Ault Reading Test (NART). Stepwise multiple regression procedures were used to determine the weights to be applied to the predictor variables.

Results.Age and premorbid IQ were found to be significantly correlated with all test variables; gender correlated significantly with most scores. Regression equations based on the 3 predictor variables explained between 10% and 30% of the variance of the range of test scores. The use of these equations in clinical practice was illustrated.

Conclusion.The significant correlations between the predictor variables and test scores justified computing a set of equations for use in interpreting data from older persons. The abnormality of the difference between predicted and obtained scores provides a convenient index of an individual's current level of neuropsychological functioning.
Functional responses of bone cells to thrombin
Authors: Pagel Charles N. , Sivagurunathan Sutharshani , Loh Lay Hoon , Tudor Elizabeth M. , Pike Robert N. , Mackie Eleanor J.
Published: August 2006

Cells responsible for the formation and maintenance of bone express thrombin-responsive members of the protease-activated receptor family of G protein-coupled receptors. Thrombin has been shown to elicit a number of functional responses in these cells, including proliferation and cytokine production in osteoblasts. Many, but not all, of the effects of thrombin on bone cells are initiated by activation of protease-activated receptor-1. A combination ofin vitroobservations and results ofin vivostudies in protease-activated receptor-1-null mice suggest that thrombin plays multiple roles in the early stages of bone healing.
Production and processing of a recombinant Fasciola hepatica cathepsin B-like enzyme (FhcatB1) reveals potential processing mechanisms in the parasite
Authors: Beckham Simone A. , Law Ruby H.-P. , Smooker Peter M. , Quinsey Noelene S. , Caffrey Conor R. , McKerrow James H. , Pike Robert N. , Spithill Terry W.
Published: August 2006

The liver fluke,Fasciola hepatica, apparently uses a number of cysteine proteases during its life cycle, most likely for feeding, immune evasion and invasion of tissues. A cathepsin B-like enzyme (herein referred to as FhcatB1) appears to be a major enzyme secreted by the invasive, newly excysted juvenile flukes of this parasite. To examine the processing mechanisms for this enzyme, a recombinant form was expressed inPichia pastorisand purified to yield a homogenous pool of the enzyme. The purified enzyme could be autoactivated at low pH via a bi-molecular mechanism, a process that was greatly accelerated by the presence of large, negatively charged molecules such as dextran sulfate. The enzyme could also apparently be processed to the correct size by an asparaginyl endopeptidase via cleavage in an unusual insertion N-terminal to the normal cleavage site used to yield the active form of the enzyme. Thus, there appear to be a number of ways in which this enzyme can be processed to its optimally active form prior to secretion byF. hepatica.
Tripeptidyl-peptidase I in health and disease
Authors: Golabek Adam A. , Kida Elizabeth
Published: August 2006

The lysosomal lumen contains numerous acidic hydrolases involved in the degradation of carbohydrates, lipids, proteins, and nucleic acids, which are basic cell components that turn over continuously within the cell and/or are ingested from outside of the cell. Deficiency in almost any of these hydrolases causes accumulation of the undigested material in secondary lysosomes, which manifests itself as a form of lysosomal storage disorder (LSD). Mutations in tripeptidyl-peptidase I (TPP I) underlie the classic late-infantile form of neuronal ceroid lipofuscinoses (CLN2), the most common neurodegenerative disorders of childhood. TPP I is an aminopeptidase with minor endopeptidase activity and Ser475 serving as an active-site nucleophile. The enzyme is synthesized as a highly glycosylated precursor transported by mannose-6-phosphate receptors to lysosomes, where it undergoes proteolytic maturation. This review summarizes recent progress in understanding of TPP I biology and molecular pathology of the CLN2 disease process, including distribution of the enzyme, its biosynthesis, glycosylation, transport and activation, as well as catalytic mechanisms and their potential implications for pathogenesis and treatment of the underlying disease. Promising data from gene and stem cell therapy in laboratory animals raise hope that CLN2 will be the first neurodegenerative LSD for which causative treatment will become available for humans.
Reward-Related Cortical Inputs Define a Large Striatal Region in Primates That Interface with Associative Cortical Connections, Providing a Substrate for Incentive-Based Learning
Authors: Haber Suzanne N. , Kim Ki-Sok , Mailly Philippe , Calzavara Roberta
Published: August 2006

The anterior cingulate and orbital cortices and the ventral striatum process different aspects of reward evaluation, whereas the dorsolateral prefrontal cortex and the dorsal striatum are involved in cognitive function. Collectively, these areas are critical to decision making. We mapped the striatal area that receives information about reward evaluation. We also explored the extent to which terminals from reward-related cortical areas converge in the striatum with those from cognitive regions. Using three-dimensional-rendered reconstructions of corticostriatal projection fields along with two-dimensional chartings, we demonstrate the reward and cognitive territories in the primate striatum and show the convergence between these cortical inputs. The results show two labeling patterns: a focal projection field that consists of densely distributed terminal patches, and a diffuse projection consisting of clusters of fibers, extending throughout a wide area of the striatum. Together, these projection fields demonstrate a remarkably large, rostral, reward-related striatal territory that reaches into the dorsal striatum. Fibers from different reward-processing and cognitive cortical areas occupy both separate and converging territories. Furthermore, the diffuse projection may serve a separate integrative function by broadly disseminating general cortical activity. These findings show that the rostral striatum is in a unique position to mediate different aspects of incentive learning. Furthermore, areas of convergence may be particularly sensitive to dopamine modulation during decision making and habit formation.
Calcium Activation of the LMO4 Transcription Complex and Its Role in the Patterning of Thalamocortical Connections
Authors: Kashani Amir H. , Qiu Zilong , Jurata Linda , Lee Soo-Kyung , Pfaff Samuel , Goebbels Sandra , Nave Klaus-Armin , Ghosh Anirvan
Published: August 2006

Lasting changes in neuronal connectivity require calcium-dependent gene expression. Here we report the identification of LIM domain-only 4 (LMO4) as a mediator of calcium-dependent transcription in cortical neurons. Calcium influx via voltage-sensitive calcium channels and NMDA receptors contributes to synaptically induced LMO4-mediated transactivation. LMO4-mediated transcription is dependent on signaling via calcium/calmodulin-dependent protein (CaM) kinase IV and microtubule-associated protein (MAP) kinase downstream of synaptic stimulation. Coimmunoprecipitation experiments indicate that LMO4 can form a complex with cAMP response element-binding protein (CREB) and can interact with cofactor of LIM homeodomain protein 1 (CLIM1) and CLIM2. To evaluate the role of LMO4in vivo, we examined the consequences of conditional loss oflmo4in the forebrain, using the Cre-Lox gene-targeting strategy. The organization of the barrel field in somatosensory cortex is disrupted in mice in whichlmo4is deleted conditionally in the cortex. Specifically, in contrast to controls, thalamocortical afferents in conditionallmo4null mice fail to segregate into distinct barrel-specific domains. These observations identify LMO4 as a calcium-dependent transactivator that plays a key role in patterning thalamocortical connections during development.
Induction of Inducible cAMP Early Repressor Expression in Nucleus Accumbens by Stress or Amphetamine Increases Behavioral Responses to Emotional Stimuli
Authors: Green Thomas A. , Alibhai Imran N. , Hommel Jonathan D. , DiLeone Ralph J. , Kumar Arvind , Theobald David E. , Neve Rachael L. , Nestler Eric J.
Published: August 2006

Previous research has shown that cAMP response element (CRE)-mediated transcription is activated in the nucleus accumbens, a major brain reward region, by a variety of environmental stimuli and contributes to neuroadaptations to these stimuli. CRE-binding protein (CREB) is the most studied activator of CRE transcription and has been implicated in this brain region as a gating mechanism for behavioral responses to emotional stimuli. Little attention, however, has been given to naturally occurring inhibitors of CRE-mediated transcription, such as the inducible cAMP early repressor (ICER), an inhibitory product of the CRE modulator gene. In the present study, we investigated the extent to which ICER is induced in the nucleus accumbens by two types of environmental stimuli, stress and amphetamine, and characterized how induction of ICER in this region affects complex behavior. We show that stress and amphetamine each induces ICER expression and that overexpression of ICER in the nucleus accumbens, using viral-mediated gene transfer, increases behavioral responses to both rewarding and aversive emotional stimuli. For example, ICER overexpression increases sensitivity to amphetamine-stimulated locomotor activity as well as to natural rewards such as sucrose and social grooming. However, ICER overexpression also increases measures of anxiety in the elevated plus maze and neophobia to novel tastes. Finally, ICER produces an antidepressant-like effect in the forced swim test, further indication of an enhanced active response to stress. These results suggest that ICER is an important mechanism for modulating CRE-mediated transcription in the nucleus accumbens.
Pharmacological Activation of mGlu4 Metabotropic Glutamate Receptors Inhibits the Growth of Medulloblastomas
Authors: Iacovelli Luisa , Arcella Antonietta , Battaglia Giuseppe , Pazzaglia Simonetta , Aronica Eleonora , Spinsanti Paola , Caruso Alessandra , De Smaele Enrico , Saran Anna , Gulino Alberto , D’Onofrio Mara , Giangaspero Felice , Nicoletti Ferdinando
Published: August 2006

Moving from the evidence that activation of type 4 metabotropic glutamate (mGlu4) receptors inhibits proliferation and promotes differentiation of cerebellar granule cell neuroprogenitors, we examined the expression and function of mGlu4 receptors in medulloblastoma cells. mGlu4 receptors were expressed in 46 of 60 human medulloblastoma samples. Expression varied in relation to the histotype (nodular desmoplastic>classic≫large-cell anaplastic) and was inversely related to tumor severity, spreading, and recurrence. mGlu4 receptors were also found in D283med, D341med, and DAOY medulloblastoma cell lines, where receptor activation with the selective enhancer PHCCC inhibited adenylyl cyclase and the phosphatidylinositol-3-kinase pathway without affecting the mitogen-activated protein kinase, Sonic Hedgehog, and Wnt pathways. Interestingly, mGlu4 receptor activation reduced DNA synthesis and cell proliferation in all three cell lines. This effect was abrogated by the phosphatidylinositol-3-kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one]. Inin vivoexperiments, repeated subcutaneous injections ofN-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) reduced the growth of D283med and DAOY cell xenografts in nude mice. More remarkably, subcutaneous or intracranial injections of PHCCC during the first week of life prevented the development of medulloblastomas in mice lacking one Patched-1 allele and x-irradiated 1 d after birth. These data suggest that mGlu4 receptor enhancers are promising drugs for the treatment of medulloblastomas.
Secretory organelles of pathogenic protozoa
Authors: Souza Wanderley de
Published: August 2006

Secretory processes play an important role on the biology and life cycles of parasitic protozoa. This review focus on basic aspects, from a cell biology perspective, of the secretion of (a) micronemes, rhoptries and dense granules in members of the Apicomplexa group, where these organelles are involved in the process of protozoan penetration into the host cell, survival within the parasitophorous vacuole and subsequent egress from the host cell, (b) the Maurer's cleft in Plasmodium, a structure involved in the secretion of proteins synthesized by the intravacuolar parasite and transported through vesicles to the erythrocyte surface, (c) the secretion of macromolecules into the flagellar pocket of trypanosomatids, and (d) the secretion of proteins which make the cyst wall of Giardia and Entamoeba, with the formation of encystation vesicles.
Sporothrix schenckii and sporotrichosis
Authors: Lopes-Bezerra Leila M. , Schubach Armando , Costa Rosane O.
Published: August 2006

For a long time sporotrichosis has been regarded to have a low incidence in Brazil; however, recent studies demonstrate that not only the number of reported cases but also the incidence of more severe or atypical clinical forms of the disease are increasing. Recent data indicate that these more severe forms occur in about 10% of patients with confirmed diagnosis. The less frequent forms, mainly osteoarticular sporotrichosis, might be associated both with patient immunodepression and zoonotic transmission of the disease. The extracutaneous form and the atypical forms are a challenge to a newly developed serological test, introduced as an auxiliary tool for the diagnosis of unusual clinical forms of sporotrichosis.
Análise crítica da utilidade do teste de clonidina - hormônio de crescimento (GH) no diagnóstico do homem infértil
Authors: Bonaccorsi Antônio Carlos , Leite Denise Boechat , Faria Júnior Raul
Published: August 2006

O presente trabalho visa analisar a confiabilidade do teste de clonidina - GH (TC-GH) no diagnóstico de uma insuficiência relativa de GH em uma população de homens inférteis. Vinte e sete pacientes foram classificados em 3 grupos de acordo com a dose de clonidina. Os grupos I (clonidina 0,150mg) e II (clonidina 0,200mg) tinham 9 e 6 pacientes oligozoospérmicos, respectivamente. O grupo III (clonidina 0,400mg) tinha 5 pacientes oligozoospérmicos (subgrupo IIIa) e 7 normozoospérmicos (subgrupo IIIb). Trinta e um TC-GH foram realizados e vinte e nove deles foram analisados; cinco (17,2%) resultaram normais (1 no grupo l, 1 no grupo III e 3 no grupo IIIb). As respostas do GH após 60, 90 e 120 minutos do estímulo não mostraram diferença significativa nos grupos l, II e III nem entre os subgrupos lIIa e IIIb. Conclui-se que o TC-GH não é de utilidade no diagnóstico de uma relativa insuficiência de GH no homem infértil, independente da dose de clonidina. A razão é a incapacidade da clonidina produzir um estímulo de GH confiável no homem adulto.
Raquitismo e osteomalacia
Authors: Mechica José B.
Published: August 2006

Raquitismo e osteomalacia são defeitos da mineralização óssea. O raquitismo é caracterizado por anormalidades na formação na placa epifisária de crescimento, com áreas não mineralizadas, desorganização da arquitetura celular e retardo na maturação óssea. A osteomalacia é caracterizada pela deficiente mineralização da matriz osteóide do osso cortical e trabecular com acúmulo do tecido osteóide pouco mineralizado. São processos que, em geral, ocorrem associados. Após o final do crescimento, com o fechamento da cartilagem epifisária, apenas a osteomalacia permanece. A falha do processo de mineralização tem como uma das principais causas a inadequada concentração extracelular de cálcio e fósforo, os dois principais componentes minerais do osso, e a falta ou comprometimento da ação dos elementos responsáveis pela sua absorção, particularmente a vitamina D. As principais manifestações clínicas como as deformidades ósseas e o atraso no crescimento, são semelhantes nos diferentes tipos de raquitismo e osteomalacia existem características que são específicas. As causas são adquiridas ou hereditárias e os recentes avanços em biologia molecular permitem a identificação dos genes envolvidos e das mutações. Essa discussão inclui os principais tipos da patologia.
Abordagem clínico-laboratorial no diagnóstico diferencial de hipercalcemia
Authors: Martin Luciana N. C. , Kayath Marcia J.
Published: August 2006

A hipercalcemia é anormalidade metabólica comum, porém pouco diagnosticada por ser freqüentemente assintomática. Aproximadamente 90% dos casos são decorrentes de hiperparatireoidismo primário (HPT) ou doença maligna complicada por hipercalcemia, estando prevalentes em pacientes ambulatoriais e hospitalizados, respectivamente. Laboratorialmente, o HPT e hipercalcemia humoral maligna apresentam algumas semelhanças, tais como: aumento do AMPc nefrogênico, hipofosfatemia e hipercalciúria. Porém, o quadro clínico da hipercalcemia associada à malignidade é mais severo e, geralmente, o paciente apresenta-se clinicamente debilitado pela doença, com múltiplas metástases. A dosagem sérica de PTH intacto (PTHi) é fundamental para o diagnóstico definitivo, estando o PTHi elevado ou normal no HPT primário, e suprimido na malignidade. Os mecanismos de hipercalcemia da doença maligna são: secreção de fatores humorais que alteram a homeostase do cálcio e fatores locais produzidos pelos tumores metastáticos ou hematológicos no osso, causando aumento da reabsorção osteoclástica. A proteína relacionada ao hormônio da paratireóide (PTHrP) tem sido implicada na maioria dos casos de hipercalcemia devido a tumores sólidos. Outros fatores como interleucina-6, fator de crescimento tumoral, fator de necrose tumoral e interleucina-1 podem modular os efeitos do PTHrP nos órgãos-alvo, e em alguns tumores, ativam diretamente o osteoctastos como por exemplo no mieloma múltiplo. A hipercalcemia pode estar menos freqüentemente associada a algumas doenças endócrinas como tireotoxicose, feocromocitoma, doença de Addison e neoplasia endócrino múltipla tipos I e IIA. Algumas drogas podem causar esse distúrbio metabólica, merecendo destaque a vitamina D, os diuréticos tiazídicos e o lítio. A sarcoidose é exemplo de doença granulomatosa que pode associar-se à hipercalcemia em 10% dos casos e hipercalciúria em 50%. O diagnóstico diferencial das hipercalcemias é essencial para que haja uma abordagem terapêutica eficaz dessa anormalidade metabólica.
The broad homeostatic role of natriuretic peptides
Authors: Maack Thomas
Published: August 2006

A brief non-inclusive review on natriuretic peptides (NP), their receptors, and their main functional properties is presented. The three main NP, atrial (ANP), brain (BNP) and C-type (CNP) are considered. Guanylyl cyclase receptors modulate all the known systemic effects of NP. Clearance receptors determine the metabolic disposal of NP and in this manner regulate their plasma levels and/or local tissue concentrations. Structure-function properties, and homeostatic properties of NP receptors are presented. ANP, which plays a major role in pressure-volume homeostasis, is discussed in relationship to its effects on renal hemodynamic and excretory functions, inhibition of the renin-angiotensin-aldosterone system, vasorelaxant, and third-spacing action. For BNP special attention is directed to its role as a negative modulator of ventricular remodeling, in view of its anti-hypertrophic, anti-fibrotic and anti-inflammatory effects in the heart. The major effect of CNP in promoting vertebral and longitudinal bone growth is briefly addressed. Finally, emphasis is placed on the recent discovery that ANP affects fat metabolism in humans due to its powerful lipolytic action.
Avaliação laboratorial e diagnóstico da resistência insulínica
Authors: Geloneze Bruno , Tambascia Marcos Antonio
Published: August 2006

Em virtude da associação entre resistência à insulina (RI) e aterosclerose, existe interesse no desenvolvimento de técnicas para se avaliar a sensibilidade à insulina (SI) in vivo. Por ser uma medida de fácil utilização em grandes populações, a insulinemia de jejum tem sido usada para avaliar a SI e fornece uma boa avaliação da sensibilidade hepática, embora não da muscular. O HOMA é um modelo matemático que prediz a SI pelas simples medidas da glicemia e da insulina no jejum e tem boa correlação com o método do clamp euglicêmico hiperinsulinêmico, considerado padrão-ouro na medida da SI. Assim, mostra-se como valiosa alternativa às técnicas mais sofisticadas e trabalhosas na avaliação da RI em humanos, como o método descrito por Bergman. Em nosso meio, encontramos o valor de corte para o diagnóstico da RI quando o Homa-IR for maior que 2,71. O QUICKI é outro método simples, baseado também nas medidas da glicemia e da insulina no jejum, que apresenta boas correlações com marcadores da síndrome metabólica, conseguindo discriminar satisfatoriamente diferentes estados de RI, como graus de obesidade e tolerância à glicose. Métodos diretos de avaliação da SI incluem o teste de tolerância à insulina (K ITT), o teste de supressão de insulina e as técnicas de clamp hiperglicêmico e euglicêmico que são descritas neste artigo. A técnica do clamp euglicêmico e hiperinsulinêmico fornece a mais pura e reprodutível informação sobre a ação da insulina. Os custos envolvidos na sua realização, entretanto, limitam o seu uso.
Prevenção do diabetes mellitus tipo 2
Authors: Lyra Ruy , Oliveira Mônica , Lins Daniel , Cavalcanti Ney
Published: August 2006

Diabetes mellitus do tipo 2 (DM2) é uma doença metabólica complexa, multifatorial e de presença global, que afeta a qualidade e o estilo de vida dos acometidos, podendo levar a uma redução pronunciada na expectativa de vida dessa população. Portadores de diabetes podem ter uma redução de 15 ou mais anos de vida, com a grande maioria morrendo em decorrência das complicações cardiovasculares. Faz-se necessário o estabelecimento de estratégias efetivas para a redução do impacto do DM2 para os próximos anos. Para isso, urge a necessidade de maior atenção no tocante às estratégias de prevenção, sobretudo para as populações de maior risco de desenvolvimento da doença. Nesse contexto, os portadores de tolerância diminuída à glicose (TDG) e glicemia de jejum alterada (GJA) devem, cada vez mais, ser alvos de estratégias de intervenção na busca de minimização de risco para o diabetes, devendo para isso terem direcionamento para a efetivação de mudanças comportamentais (fatores dietoterápicos e prática de atividade física) e, quando necessário e aprovado, o uso de agentes farmacológicos. Estudos conduzidos pelo mundo têm confirmado a eficácia do uso de estratégias comportamentais e mesmo do uso de agentes farmacológicos para a prevenção de DM2.
Citocinas, disfunção endotelial e resistência à insulina
Authors: Carvalho Maria Helena C. de , Colaço André Luiz , Fortes Zuleica Bruno
Published: August 2006

A disfunção endotelial está associada a diversas alterações vasculares, como a aterosclerose, hipertensão arterial, hiperlipidemia e diabetes mellitus, que têm em comum a resistência à insulina (RI). Citocinas são proteínas de baixo peso molecular, com diversas funções metabólicas e endócrinas, que participam da inflamação e resposta do sistema imune. Várias dessas citocinas são consideradas como fatores de risco independentes para doenças da artéria coronária e cerebrovascular. As principais fontes de citocinas (adipocinas) são os tecidos adiposos subcutâneo e visceral. Assim, aumento da massa de tecido adiposo está associado com alterações da produção de adipocina com aumento da expressão de fator de necrose tumoral alfa (TNF-alfa), interleucina 6 (IL-6), inibidor do fator ativador de plasminogênio 1 (PAI-1), e diminuição da expressão de adiponectina no tecido adiposo. A condição pró-inflamatória associada a essas alterações sugere ligação entre RI e disfunção endotelial no estágio inicial do processo de aterosclerose, em indivíduos obesos e em pacientes diabéticos tipo 2. A redução da massa de tecido adiposo, por redução de peso associada a exercício físico, reduz TNF-alfa, IL-6 e PAI-1, aumenta adiponectina, e melhora tanto a sensibilidade à insulina quanto a função endotelial. A interação entre adipocinas e insulina no controle da função endotelial será discutida, bem como o conceito de que a alteração da secreção de adiponectinas na RI e/ou obesidade piora a função endotelial, além de diminuir ainda mais a sensibilidade à insulina.
Que valores devem ser adotados para o diagnóstico de microalbuminúria no diabete melito?
Authors: Leitão Cristiane B. , Canani Luís Henrique , Bolson Patrícia B. , Molon Marcel P. , Silveiro Sandra Pinho , Gross Jorge Luiz
Published: August 2006

A nefropatia diabética (ND) é uma complicação do diabete melito (DM) associada a grande morbi-mortalidade. A identificação de indivíduos de maior risco tornará a sua prevenção mais efetiva. A excreção urinária de albumina (EUA) ainda é o melhor marcador da instalação e progressão da ND, além de ser fator de risco para o desenvolvimento de doenças macrovasculares. A albuminúria nos limites superiores da normalidade (< 20 µg/min) já está associada ao desenvolvimento de micro e macroalbuminúria. A EUA apresenta correlação contínua com o desenvolvimento de doença renal e cardiovascular, sem um ponto determinado a partir do qual ocorre um aumento mais importante do risco. No entanto, na prática clínica se faz necessário o estabelecimento de um valor crítico para guiar o tratamento dos pacientes. Algumas evidências apontam para valores de EUA ente 5 e 10 µg/min como um novo ponto de corte para o diagnóstico de microalbuminúria. Concluindo, a associação entre a EUA e o desfecho renal e cardiovascular parece ser contínuo e já está presente até mesmo com níveis de EUA considerados normais. A adoção de um valor entre 5 e 10 µg/min como de risco poderá identificar os pacientes que deveriam receber tratamento mais precoce e agressivo dos fatores de risco modificáveis.
Pharmacological treatment of obesity
Authors: Mancini Marcio C. , Halpern Alfredo
Published: August 2006

This review offers an overview of physiological agents, current therapeutics, as well as medications, which have been extensively used and those agents not currently available or non-classically considered anti-obesity drugs. As obesity - particularly that of central distribution - represents an important triggering factor for insulin resistance, its pharmacological treatment is relevant in the context of metabolic syndrome control. The authors present an extensive review on the criteria for anti-obesity management efficacy, on physiological mechanisms that regulate central and/or peripheral energy homeostasis (nutrients, monoamines, and peptides), on beta-phenethylamine pharmacological derivative agents (fenfluramine, dexfenfluramine, phentermine and sibutramine), tricyclic derivatives (mazindol), phenylpropanolamine derivatives (ephedrin, phenylpropanolamine), phenylpropanolamine oxytrifluorphenyl derivative (fluoxetine), a naftilamine derivative (sertraline) and a lipstatine derivative (orlistat). An analysis of all clinical trials - over ten-week long - is also presented for medications used in the management of obesity, as well as data about future medications, such as a the inverse cannabinoid agonist, rimonabant.
Expression of the p53 protein and clinical and pathologic correlation in adenocarcinoma of the rectum
Authors: Jurach Márcia Teresinha , Meurer Luise , Moreira Luis Fernando
Published: August 2006

BACKGROUND: p53 is a tumor suppressor gene that has been implicated in the pathogenesis of a wide range of tumors, including colorectal cancer. AIM: To evaluate the prognostic significance of p53 protein expression, and to correlate with clinical and pathologic variables as well as survival. PATIENTS AND METHODS: Immunohistochemical staining for p53 protein was performed in a series of 83 patients with rectal cancer with a follow-up of at least 5 years. RESULTS: Expression of nuclear protein was positive in 36 (43.4%) of the tumors. We found association between positive p53 and death, local recurrence, distant metastasis and overall recurrence and we also found association between p53 and death, local recurrence, metastasis and overall recurrence when analysis was adjusted to Astler-Coller stage and grade of differentiation. CONCLUSION: p53 immunoexpression has shown to be an independent prognostic factor in these series.
Relação entre o tamanho de hérnia hiatal e tempo de exposição ácida esofágica nas doenças do refluxo erosiva e não-erosiva
Authors: Abrahão Jr. Luiz João , Lemme Eponina Maria de Oliveira , Carvalho Beatriz Biccas , Alvariz Angela , Aguero Gustavo Carlos Calcena , Schechter Rosana Bihari
Published: August 2006

RACIONAL: Nos últimos anos, estudos têm demonstrado a importância da hérnia hiatal na etiopatogenia da doença do refluxo gastroesofágico, atuando por vários mecanismos, sendo enfatizado que quanto maior a hérnia, maior seria a possibilidade de refluxo e esofagite. OBJETIVOS: Avaliar por parâmetros de pHmetria prolongada, se a presença de hérnias volumosas se correlaciona com maior intensidade do refluxo, em pacientes com a doença do refluxo erosiva e doença do refluxo não-erosiva. PACIENTES E MÉTODOS: Foram revistas as pHmetrias prolongadas anormais consecutivas de pacientes em investigação de doença do refluxo gastroesofágico (pirose como queixa principal) e analisadas as percentagens de tempo total (%TT), em posição ereta (%TE) e posição supina (%TS) com pH <4. Todos haviam realizado previamente endoscopia digestiva alta. Selecionaram-se pacientes com doença do refluxo erosiva (esofagite pela classificação de Savary-Miller) e com doença do refluxo não-erosiva (sem esofagite, com pHmetria prolongada anormal), todos com hérnia hiatal. Considerou-se hérnia hiatal não volumosa aquelas entre 2 e <5 cm e hérnia hiatal volumosa quando de tamanho =/>5 cm. RESULTADOS: Cento e noventa e dois pacientes preencheram os critérios de inclusão, sendo 115 com doença do refluxo erosiva e 77 com doença do refluxo não-erosiva. No primeiro grupo, 94 (81%) pacientes apresentavam hérnias hiatais não-volumosas, enquanto que 21 (19%) apresentavam hérnias hiatais volumosas. No grupo com doença do refluxo não-erosiva, 66 (85%) pacientes apresentavam hérnia hiatal não-volumosa e 11 (15%) hérnia hiatal volumosa. Na doença do refluxo erosiva, as %TT, %TE e %TS foram de 13,1 + 7,1, 13,4 + 7,4 e 12,3 + 11,5 nas hérnias hiatais não-volumosas, aumentando para 20,2 + 12,3, 17,8 + 14,1 e 20,7 + 14,1 nas hérnias hiatais volumosas, respectivamente, sendo este aumento estatisticamente significante nos tempos total e supino. Na doença do refluxo não-erosiva, as %TT, %TE e %TS foram de 9,6 + 4,8, 10,8+ 6,8 e 8,6 + 7,3 nas hérnias hiatais não volumosas e de 14,6 + 13,3, 11,2 + 7,5 18,1 + 21,0 nas hérnias volumosas, respectivamente, com significância semelhante à anterior. CONCLUSÃO: As hérnias volumosas aumentam o tempo de exposição ácida esofágica exclusivamente na posição supina nos pacientes com doença do refluxo erosiva e doença do refluxo não-erosiva.
Teste respiratório da 13C-metacetina na doença hepática crônica pelo vírus C
Authors: Oliveira Ana Cláudia , Reber Marialice , Lanzoni Valéria , Ferraz Maria Lúcia , Parise Edison Roberto
Published: August 2006

RACIONAL: O teste respiratório da metacetina marcada com carbono 13 (13C-metacetina) é método não-invasivo que permite examinar a função hepática microssomal, permitindo avaliação quantitativa da massa hepática funcional. OBJETIVO: Avaliar a utilidade clinica do teste respiratório da 13C-metacetina na avaliação de pacientes com doença crônica do fígado pelo vírus da hepatite C. CASUÍSTICA E MÉTODOS: Setenta e oito pacientes com hepatite crônica C e 13 indivíduos saudáveis pareados por sexo e idade foram estudados. Pacientes infectados cronicamente pelo vírus C foram classificados como portadores de hepatite crônica (n = 51) ou cirrose hepática (n = 27, sendo 7 deles classificados como descompensados pela presença de ascite, icterícia e/ou encefalopatia). Pacientes co-infectados HbsAg/HIV, em uso crônico de álcool, com outras doenças crônicas ou em uso de medicamentos que pudessem interferir com a atividade do citocromo P450, foram excluídos. O estádio e a atividade da doença nos fragmentos de biopsia foram determinados de acordo com os critérios da Sociedade Brasileira de Hepatologia. O teste respiratório da 13C-metacetina foi realizado com 75 mg de 13C-metacetina e a concentração de 13CO2 no ar expirado foi medido através de espectrometria infravermelha não dispersiva. Foram calculados o "delta over baseline" e o percentual de recuperação cumulativo do 13CO2 aos 40 (teste respiratório da 13C-metacetina 40 min) e aos 120 minutos (teste respiratório da 13C-metacetina 120 min). RESULTADOS: Os parâmetros do teste respiratório da 13C-metacetina se correlacionaram com avaliação estrutural histológica, mas não com a atividade necroinflamatória no tecido hepático, sendo que a melhor correlação foi obtida entre o grau de estádio e o teste respiratório da 13C-metacetina 120 min. Os valores médios do teste respiratório da 13C-metacetina 120 min foram significantemente mais reduzidos nos grupos cirróticos (19,2 ± 7,1% para cirróticos compensados e 14,7 ± 4,0% para os cirróticos descompensados) que nos grupos controle (29,9 ± 4,5%) e com hepatite crônica (27,8 ± 6,1%). A melhor acurácia no diagnóstico de cirrose entre os portadores de hepatite crônica C foi encontrada para o teste respiratório da 13C-metacetina 120 min com 81% de sensibilidade e 77% de especificidade. CONCLUSÃO: O teste respiratório da 13C-metacetina se correlaciona com alterações estruturais encontradas na hepatite crônica pelo vírus C e o percentual de recuperação de 13CO2 aos 120 minutos é um sensível parâmetro para identificar a presença de cirrose nesses pacientes.
The relation between EEG prefrontal asymmetry and subjective feelings of mood following 24 hours of sleep deprivation
Authors: Ferreira Camila , Deslandes Andréa , Moraes Helena , Cagy Maurício , Basile Luiz Fernando , Piedade Roberto , Ribeiro Pedro
Published: August 2006

Several studies have investigated the relationship between asymmetrical EEG activity over the frontal cortex and mood. This study aimed at investigating the association between state fluctuations in frontal alpha EEG asymmetry and state changes followed by 24 h of sleep deprivation (SD). Our results show that sleep deprivation caused a significant alteration in the asymmetry values. Activation shifted from the left hemisphere, before SD, to the right hemisphere, after SD, in all frontal electrode pairs. In addition, according to the self-rating scale of SD-related mood effects, subjects became significantly less alerted and active, and sleepier. According to these results, increased right prefrontal activation might be potentially associated with the negative mood states typically seen after sleep deprivation, although the causal relationship is still uncertain. However, more studies will be necessary to establish the viability of EEG asymmetry and the cerebral lateralization hypothesis to explain the SD-related affective changes.