Enfermedad cardiovascular aterosclerótica y sexualidad / Atherosclerotic Cardiovascular Disease and Sexuality

La enfermedad cardiovascular aterosclerótica es la primera causa de muerte en todo el mundo, y la principal causa de años de vida perdidos por discapacidad (AVADs) en los adultos. Sus factores de riesgo son muy prevalentes en la población, y su ocurrencia se ha asociado con disfunción sexual tanto en hombres como en mujeres, debido a que comparten un mecanismo fisiopatológico similar en el caso de la disfunción eréctil en los hombres y potencialmente en la disfunción sexual femenina. Además, los trastornos mentales asociados (principalmente ansiedad y depresión) y los efectos adversos de los medicamentos antihipertensivos y antidepresivos también contribuyen a las disfunciones sexuales. Por otro lado, los inhibidores de la fosfodiesterasa 5 (iFDE5s) han demostrado seguridad y beneficios cardiovasculares en los hombres, y en las mujeres hay evidencia creciente de su utilidad en las disfunciones sexuales. En esta revisión, se presentan las implicaciones de la enfermedad cardiovascular aterosclerótica y su tratamiento en la vida sexual de hombres y mujeres, los efectos cardiovasculares de los tratamientos de las disfunciones sexuales, y la consejería a los pacientes.

Atherosclerotic cardiovascular disease is the leading cause of death worldwide and the leading cause of disability-adjusted life years (DALYs). Its risk factors are very prevalent in the population, and its occurrence has been associated with sexual dysfunction in both men and women, because they share a similar pathophysiological mechanism in the case of erectile dysfunction in men and potentially in female sexual dysfunction. Furthermore, associated mental disorders (mainly anxiety and depression) and the adverse effects of antihypertensive drugs and antidepressants also contribute to sexual dysfunction. On the other hand, phosphodiesterase 5 inhibitors (PDE5is) have shown safety and cardiovascular benefits in men, and in women there is growing evidence of their usefulness in female sexual dysfunctions. The present review describes the implications of atherosclerotic cardiovascular disease and its treatment on the sexual lives of men and women, the cardiovascular effects of the treatments for sexual dysfunctions, and patient counseling.

Positive inotropic effect of phosphodiesterase type 9 inhibitor PF-04449613 in rats and its underlying mechanism / 生理学报

This study aimed to explore the positive inotropic effect of phosphodiesterase type 9 (PDE9) inhibitor PF-04449613 in ratsand its cellular and molecular mechanisms. The heart pressure-volume loop (P-V loop) analysis was used to detect the effects of PF-04449613 on rat left ventricular pressure-volume relationship, aortic pressures and peripheral vessel resistance in healthy rats. The Langendorff perfusion of isolated rat heart was used to explore the effects of PF-04449613 on heart contractility. The cardiomyocyte sarcoplasmic reticulum (SR) Ca

Mecanismo de Frank Starling: una visión aplicada en la erección del pene / Frank-Starling Mechanism: A Vision Applied To Penile Erection

El mecanismo de Frank-Starling es un concepto básico de la fisiología cardíaca y su aprendizaje. Constituye la base fundamental para el entendimiento del funcionamiento del corazón y patologías prevalentes y con alta morbimortalidad como lo es la insuficiencia cardíaca. Por lo cual, su relación con un proceso más interactivo como la erección del pene, podría asegurar un aprendizaje perdurable y práctico. La relación se fundamentó en el reemplazo del eje X de la curva por precarga en el caso del corazón y estimulación en el caso del pene, para así lograr una relación incluso con la disfunción eréctil, que sería el equivalente a la insuficiencia cardíaca. De esa manera, se encontró que a mayor estimulación hay mayor erección y a mayor precarga hay mayor eyección ventricular, teniendo ambas curvas una meseta. Asímismo, farmacológicamente, se encontró relación con el uso de estimulación ß-adrenérgica y de inhibidores selectivos de la fosfodiesterasa tipo 5 como el sildenafil, los cuales desplazan la curva hacia arriba y a la izquierda.

The Frank-Starling mechanism is a basic concept of cardiac physiology and the fundamental basis for understanding the cardiac performance and prevalent disorders at risk of high morbidity and mortality, such as heart failure. Therefore, its relation with an interactive process like penile erection may enable deeper insight into cardiac physiology. The X-axis of Frank-Starling's curve was changed from ventricular end-diastolic volume to stimulation, to achieve a relation that includes erectile dysfunction, which is the equivalent of heart failure. A direct relationship was found between stimulation and erection, as well as end-diastolic volume and ventricular ejection with a plateau in both curves. Likewise, pharmacologically, a relation was identified with the use of ß-adrenergic and selective inhibitor of phosphodiesterase (PDE) type 5 like sildenafil, which shift leftward and upward the Frank-Starling curve

Acute kidney injury due to systemic Loxoscelism: a cross-sectional study in Northeast Brazil

Abstract INTRODUCTION: Loxoscelism is a clinical condition involving spiders of the genus Loxosceles. One of the most severe complications is acute kidney injury (AKI). This study aimed to investigate AKI and other complications associated with loxoscelism. METHODS: We analyzed cases diagnosed with loxoscelism in an area where most accidents were caused by Loxosceles amazonica from January 2010 to December 2015. AKI was defined according to the KDIGO criteria. RESULTS: Forty-five patients were recorded: 95.6% presented characteristic necrotic skin lesions and 13.3% AKI. CONCLUSIONS: Loxoscelism could cause kidney involvement which is uncommon and could lead to the death of these patients.

The hepatic ectonucleotide pyrophosphatase/phosphodiesterase 1 gene mRNA abundance is reduced by insulin and induced by dexamethasone

Hormones regulate hepatic gene expressions to maintain metabolic homeostasis. Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been thought to interfere with insulin signaling. To determine its potential role in the regulation of metabolism, we analyzed its gene (Enpp1) expression in the liver of rats experiencing fasting and refeeding cycles, and in primary rat hepatocytes and human hepatoma HepG2 cells treated with insulin and dexamethasone using northern blot and real-time PCR techniques. Hepatic Enpp1 expression was induced by fasting and reduced by refeeding in the rat liver. In primary rat hepatocytes and HepG2 hepatoma cells, insulin reduced Enpp1 mRNA abundance, whereas dexamethasone induced it. Dexamethasone disrupted the insulin-reduced Enpp1 expression in primary hepatocytes. This is in contrast to the responses of the expression of the cytosolic form of phosphoenolpyruvate carboxykinase gene to the same hormones, where insulin reduced it significantly in the process. In addition, the dexamethasone-induced Enpp1 gene expression was attenuated in the presence of 8-Br-cAMP. In conclusion, we demonstrated for the first time that hepatic Enpp1 is regulated in the cycle of fasting and refeeding, a process that might be attributed to insulin-reduced Enpp1 expression. This insulin-reduced Enpp1 expression might play a role in the development of complications in diabetic patients.

Effect of EphB4/EphrinB2 reverse signal on angiogenesis induced by Xuefu Zhuyu Capsule () containing serum in human microvascular endothelial cell 1 / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Xuefu Zhuyu Capsule ()-containing serum (XFZY-CS) on EphB4/ephrinB2 and its reverse signal in human microvascular endothelial cell-1 (HMEC-1).</p><p><b>METHODS</b>XFZY-CS and the blank control serum were collected. HMEC-1 cells were randomly assigned to 6 groups including the concentration 1.25%, 2.5%, and 5% XFZY-CS groups and their blank serum control ones. The angiogenesis effect of XFZY-CS was tested with an in vitro tube formation assay and the best condition of pro-angiogenesis was determined. The effect of XFZY-CS on EphB4/ephrinB2 and the reverse signal were determined by Western blot and real-time quantitative polymerase chain reaction, respectively; we also confifirmed the results through activating and inhibiting the reverse signal by EphB4/fc and pyrophosphatase/ phosphodiesterase2 (PP2).</p><p><b>RESULTS</b>XFZY-CS promoted angiogenesis at the concentration of 2.5% corresponding serum after being cultured for 48 h, while inhibited angiogenesis at the concentration of 5% after culturing for 48 and 72 h. Under the 2.5% serum concentration, XFZY up-regulated the expression of EphB4-mRNA at 12 h (P<0.05), and down-regulates its expression at 24 h (P<0.01). Protein expression of EphB4 was apparently up-regulated at 12 h and down-regulated at 24 h. The phosphorylation of ephrinB2 increased at 9 h (P<0.05). In addition, 2.5% XFZY-CS played a similar role as the reverse signaling activator EphB4/Fc ranging from 0.5 to 5 μg/mL (P>0.05). XFZY-CS also reduced the inhibitive effect of PP2 in limited periods.</p><p><b>CONCLUSIONS</b>EphB4/ephrinB2 was the upstream signal in the process of angiogenesis and its reverse signaling was responsible for XFZY's effect on promoting angiogenesis.</p>

Basophil Activation Test for Chronic Urticaria

No abstract available.

Sudden Cardiac Death in Brazil: A Community-Based Autopsy Series (2006-2010) / Morte Súbita Cardíaca no Brasil: Análise dos Casos de Ribeirão Preto (2006-2010)

Background: Sudden cardiac death (SCD) is a sudden unexpected event, from a cardiac cause, that occurs in less than one hour after the symptoms onset, in a person without any previous condition that would seem fatal or who was seen without any symptoms 24 hours before found dead. Although it is a relatively frequent event, there are only few reliable data in underdeveloped countries. Objective: We aimed to describe the features of SCD in Ribeirão Preto, Brazil (600,000 residents) according to Coroners’ Office autopsy reports. Methods: We retrospectively reviewed 4501 autopsy reports between 2006 and 2010, to identify cases of SCD. Specific cause of death as well as demographic information, date, location and time of the event, comorbidities and whether cardiopulmonary resuscitation (CPR) was attempted were collected. Results: We identified 899 cases of SCD (20%); the rate was 30/100000 residents per year. The vast majority of cases of SCD involved a coronary artery disease (CAD) (64%) and occurred in men (67%), between the 6th and the 7th decades of life. Most events occurred during the morning in the home setting (53.3%) and CPR was attempted in almost half of victims (49.7%). The most prevalent comorbidity was systemic hypertension (57.3%). Chagas’ disease was present in 49 cases (5.5%). Conclusion: The majority of victims of SCD were men, in their sixties and seventies and the main cause of death was CAD. Chagas’ disease, an important public health problem in Latin America, was found in about 5.5% of the cases. .

Fundamento: Morte súbita cardíaca (MSC) é um evento súbito e inesperado, de causa cardiovascular, que ocorre em menos de uma hora após o início dos sintomas, em indivíduo sem qualquer condição clínica prévia potencialmente fatal ou assintomático nas últimas 24 horas antes do óbito, em caso de morte não testemunhada. Apesar de ser um evento relativamente frequente, há poucos dados confiáveis na literatura sobre países em desenvolvimento. Objetivo: Descrever as características da MSC em Ribeirão Preto (SP 600.000 habitantes) baseando-se nos relatórios de autopsias do Serviço de Verificação de Óbitos do Interior. Métodos: Foram revisados retrospectivamente 4.501 relatórios de autopsias entre 2006 e 2010, para identificar casos de MSC. Foram coletados dados como causa específica do óbito, características demográficas e comorbidades das vítimas, data, local e hora do evento, e se foram realizadas manobras de ressuscitação cardiopulmonar (RCP). Resultados: Foram identificados 899 casos de MSC (20%; razão 30/100.000 habitantes por ano). A principal causa de MSC foi doença arterial coronariana (DAC - 64%), acometendo homens (67%) entre a sexta e a sétima década de vida. A maior parte dos eventos ocorreu durante a manhã, no domicílio (53,3%), e a RCP foi realizada em quase metade das vítimas (49,7%). A comorbidade mais prevalente foi hipertensão arterial sistêmica (57,3%). Doença de Chagas foi detectada em 49 casos (5,5%). Conclusão: A maioria dos casos de MSC ocorreu por DAC em homens entre a sexta e a sétima década de vida. Doença de Chagas, um importante problema de saúde pública na América Latina, foi detectada em 5,5% dos casos. .

Specific Expression of Aplysia Phosphodiesterase 4 in Bag Cells Revealed by in situ Hybridization Analysis

Phosphodiesterases (PDEs) play a key role in the regulation of cyclic adenosine monophosphate (cAMP), which in turn mediates various cellular functions including learning and memory. We previously cloned and characterized three PDE4 isoforms (ApPDE4) from Aplysia kurodai. Using reverse transcription polymerase chain reaction (RT-PCR), we found that ApPDE4 isoforms are primarily expressed in the central nervous system. However, the detailed distribution of ApPDE4 mRNA in Aplysia individual ganglions was not evident. In this study, to determine the distribution of ApPDE4 mRNAs in Aplysia ganglions, we performed in situ hybridization (ISH) using a probe targeting ApPDE4, including the PDE catalytic domain. Interestingly, we found the strongest ISH-positive signals in the symmetrical bag cell clusters of the abdominal ganglion. The R2, R14, L7, L2 and L11 neurons in the abdominal ganglion, LP1 neuron in pleural ganglion, and metacerebral (MCC) neurons were ISH-positive. Mechanosensory neurons of the sensory cluster were also stained on the ventral aspect of the right and left pleural ganglia. Taken together, we found the detailed distribution of ApPDE4 mRNA in Aplysia ganglion and support their roles in serotonin (5-HT)-induced synaptic facilitation of Aplysia mechanosensory neurons.

Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root cementogenesis / 国际口腔科学杂志·英文版

Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate (Pi) to mineral inhibitor pyrophosphate (PPi), where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enpp1 null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enpp1 gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected.

Antifibrotic effect of curcumin on thioacetamide induced liver fibrosis

The objective of the present study was to elucidate whether serum ATX activity might be a target for regulation of liver fibrosis and to evaluate the hepatoprotective and antifibrotic effect of curcumin in TAA induced liver fibrosis in rats. Therefore 40 healthy adult albino rats, divided into 4 groups [10 rats in each]. Rats in the 2[nd] group received curcumin [500 mg/kg b. wt /orally every day], the 3[rd] group injected by thioacetamide [TAA] intraperioteneal [250 mg/kg b. wt] three times a week, the 4[th] group injected by TAA intraperioteneal [250 mg/kg b. wt] three times a weeks and received curcumin orally [500 mg/kg b. wt every day]. The changes in body weight index and histopathological examination. In addition, selected biochemical parameters were also determined. The present study revealed that, oral supplementation of curcumin causing increase of liver weight index, autotaxin [ATX], HDL-c level and decrease of total protein, urea, creatinine and ammonia, total cholesterol, LDL-c and triacylglycerols. Treatment with TAA induced increase in the liver weight index, ATX, ALT, triacylglycerols, ammonia levels and decrease in serum proteins, urea, total cholesterol, HDL-c and LDL-c levels. Histopathological examination revealed severs necrosis, inflammatory cellular infiltration and nodules in TAA group. While the supplementation of rats with TAA and curcumin orally together resulted in increase in liver weight index, ATX, ALT, triacylglycerols levels and decrease in serum total protein, urea, total cholesterol, HDL-c, LDL-c concentration moreover, revealed mild inflammation and necrosis by histopathological examination. Conclusively, the use of curcumin ameliorated the effect of TAA induced liver fibrosis but cannot reach the normal levels

Changes in expression of phospholipase C-gamma1(tyr783) in young rat condylar cartilage during functional mandibular protraction / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the changes in the expression of phospholipase C-gamma1tyr783 (PLC-γ1tyr783) in the condylar cartilage of a young rat during functional mandibular protraction. This work also explores the function of PLC-γ1tyr783 in the rat mandibular condylar cartilage bone remodeling, which could provide experimental evidence for clinical bone ortho- pedic work.</p><p><b>METHODS</b>A total of 60 four-week-old male Sprague-Dawley (SD) rats were used in this study. The rats were divided equally and randomly into experimental group and control group. The functional appliances that were fitted to the upper incisors of the animals in the experimental group were worn 24 h a day after the rats were fed for 7 d with homemade pellet feed. The animals in the experimental group, along with their matched controls, were sacrificed after 1, 3, 7, 14, 21, and 28 d. The bilateral condylar was fixed, decalcified, dehyded, and then conventional paraffin embedded. Immunohisto- chemistry of PLC-γ1tyr783 was applied to observe its express distribution and variation.</p><p><b>RESULTS</b>The expression of PLC-γ1tyr783 decreased gradually in the control group, which showed age-related changes (P > 0.05). On the 14th day, PLC-γ1tyr783 expres- sion in the experimental group was significantly higher than that in the control group. PLC-γ1tyr783 expression began to appear statistically and significantly different between the two groups (P < 0.01).</p><p><b>CONCLUSION</b>PLC-γ1tyr783 is involved in the bone remodeling process of the rat condylar cartilage after functional mandibular-protraction.</p>

Increased Level of Basophil CD203c Expression Predicts Severe Chronic Urticaria

Increased FcepsilonR1alpha expression with upregulated CD203c expression on peripheral basophils is seen in patients with chronic urticaria (CU). However, there has been no published report on the association between CD203c expression level and clinical disease activity in CU patients. To investigate whether the increase of basophil activation is associated with the disease activity of CU, we measured basophil CD203c expression using a tricolor flow cytometric method in 82 CU patients and 21 normal controls. The relationship between the percentage of CD203c-expressing basophils and clinical parameters was analyzed. The mean basophil CD203c expression was significantly higher in CU patients than in healthy controls (57.5% vs 11.6%, P or = 72% basophil CD203c expression and urticaria activity score (UAS)> or = 13 were significant predictors of severe CU (P = 0.005 and P = 0.032, respectively). These findings suggest that the quantification of basophil activation with CD203c at baseline may be used as a potential predictor of severe CU requiring another treatment option beyond antihistamines.

Impact of ENPP1 K121Q on Change of Insulin Resistance after Web-Based Intervention in Korean Men with Diabetes and Impaired Fasting Glucose

Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been studied in relation to type 2 diabetes mellitus (T2DM) and insulin resistance (IR). We hypothesized that the difference in genotype may be one of the factors that affect the outcome of intervention. We genotyped 448 men with fasting glucose> or =5.6 mM/L, including 371 in subjects with K allele (KK) (69 control group [CG]; and 302 intervention group [IG]) and 77 in subjects with Q allele (KQ+QQ) (13 CG and 64 IG). The web-based intervention based on a lifestyle modification was delivered by e-mail once a month for 10 months. In the KK, IG demonstrated significantly decreased levels of fasting serum insulin (FSI) as compared to CG and homeostasis model of assessment of insulin resistance (HOMA-IR). In the KQ+QQ IG group, hemoglobin A1c (HbA1c), FSI and HOMA-IR were significantly decreased, and showed further reduction in the HOMA-IR than KQ+QQ CG. After analysis of covariance, K121Q did significantly influence the change of HbA1c in CG after appropriate adjustment. In a multivariate model, BMI change predicted HOMA-IR change (adjusted beta=0.801; P=0.022) in KK IG subjects with T2DM. ENPP1 K121Q did not influence the change in IR. However, individuals with T2DM carrying the K121 variant are very responsive to the effect of BMI reduction on HOMA-IR.

First report of in vitro selection of RNA aptamers targeted to recombinant Loxosceles laeta spider toxins

BACKGROUND: Loxoscelism is the envenomation caused by the bite of Loxosceles spp. spiders. It entails severe necrotizing skin lesions, sometimes accompanied by systemic reactions and even death. There are no diagnostic means and treatment is mostly palliative. The main toxin, found in several isoforms in the venom, is sphingomyelinase D (SMD), a phospholipase that has been used to generate antibodies intended for medical applications. Nucleic acid aptamers are a promising alternative to antibodies. Aptamers may be isolated from a combinatorial mixture of oligonucleotides by iterative selection of those that bind to the target. In this work, two Loxosceles laeta SMD isoforms, Ll1 and Ll2, were produced in bacteria and used as targets with the aim of identifying RNA aptamers that inhibit sphingomyelinase activity. RESULTS: Six RNA aptamers capable of eliciting partial but statistically significant inhibitions of the sphingomyelinase activity of recombinant SMD-Ll1 and SMD-Ll2 were obtained: four aptamers exert ~17% inhibition of SMD-Ll1, while two aptamers result in ~25% inhibition of SMD-Ll2 and ~18% cross inhibition of SMD-Ll1. CONCLUSIONS: This work is the first attempt to obtain aptamers with therapeutic and diagnostic potential for loxoscelism and provides an initial platform to undertake the development of novel anti Loxoscelesvenom agents.

Expression of ectonucleotide pyrophosphatase-1 in end-plate chondrocytes with transforming growth factor beta 1 siRNA interference by cyclic mechanical tension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)-1 is a membrane-bound protein that catalyzes the hydrolysis of extracellular nucleoside triphosphates to monophosphate and extracellular inorganic pyrophosphate (ePPi). Mechanical stimulation regulates ENPP-1 expression. This study sought to investigate the changes in ENPP-1 expression after stimulation using cyclic mechanical tension (CMT).</p><p><b>METHODS</b>Rat end-plate chondrocytes were cultured and subjected to CMT (at 3%, 6%, and 9% elongation) for 20, 40, and 60 minutes to observe changes in the expression of ENPP-1. To investigate the pathway, end-plate chondrocytes were exposed to 10 ng/ml of transforming growth factor beta 1 (TGF-β1), TGF-β1 siRNA, or a specific extracellular signalregulated kinase (ERK)1/2 inhibitor, U0126, in addition to CMT. Changes in ENPP-1 expression were measured by reverse transcription PCR (RT-PCR) and Western blotting.</p><p><b>RESULTS</b>We observed the largest increase in ENPP-1 expression following 3% elongation CMT stimulation. ENPP-1 expression was also increased when end-plate chondrocytes were exposed to 10 ng/ml of TGF-β1, but decreased after TGF-β knockdown with siRNA. ERK1/2 phosphorylation was activated after 3% elongation for 40 minutes, and the stimulatory effect of TGF-β1 on ENPP-1 mRNA and protein expression was inhibited by the suppression of the ERK1/2 pathway using U0126.</p><p><b>CONCLUSION</b>CMT increases the expression of ENPP-1 in end-plate chondrocytes in a manner likely dependent on TGF-β induction by the ERK1/2 signaling pathway.</p>

Quantitative expression analysis of two NAGPA isoforms in multiple human cDNA tissue panels / 동물의과학연구지

Uncovering enzyme (UCE), encoded by the human NAGPA, is a trans-Golgi enzyme that adds the mannose-6-phosphate recognition tag on lysosomal enzymes destined for the lysosome. Mutations in NAGPA are known to cause stuttering, a common speech disorder with unknown etiology. The human NAGPA gene is transcribed into two different forms, probably due to alternative splicing. One of them, known as a brain isoform, is lacking exon 8 (102-bp). We performed quantitative real-time PCR for the NAGPA brain and non-brain isoforms in a cDNA panel originating from 16 human tissues and 24 sub-brain regions. According to our findings, the relative quantity of the NAGPA brain isoform in the brain was 4.7 times more than that in the control cDNA, a pooled mixture of equal amounts of cDNAs from the 16 different tissues. Further analysis using the cDNA panel originating from 24 different sub-brain regions revealed that the cerebral cortex contained the largest amount of NAGPA brain isoform. Relative quantity in the cerebral cortex was 8.6 times more than that in the control cDNA (P=0.00004). The lowest quantity of this isoform was detected in cDNA from the pituitary gland. In conclusion, findings of the current study suggest that the cerebral cortex, expressing the highest quantity of the NAGPA brain isoform, might be the region associated with speech function.