Prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil.

Chemokines are low-molecular weight proteins that play a key role in inflammatory processes. Genomic variations in chemokine receptors are associated with the susceptibility to various diseases. Polymorphisms in chemokine receptor type 5 (CCR5)-Δ32 and CCR2-V64I are related to human immunodeficiency virus infection resistance, which has led to genetic association studies for several other diseases. Given the heterogeneous distribution of these polymorphisms in different global populations and within Brazilian populations, we analyzed the prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil. The study included 223 individuals from the general population of the city of Parnaíba, Piauí, who had a mean age of 73 years. Of these individuals, 37.2% were men and 62.8% were women. Polymorphisms were analyzed using DNA extracted from peripheral blood leukocytes by using polymerase chain reaction alone (CCR5-Δ32) or accompanied by restriction endonuclease digestion (CCR2-V64I). In both cases, the genotypes were determined using 8% polyacrylamide gel electrophoresis and silver nitrate staining. The population conformed to Hardy-Weinberg equilibrium for both the loci studied. No individuals were homozygous for allele-Δ32, which was present in 1.8% of the population, whereas allele-64I was present in 13.9% of the participants studied; 74.9% were homozygous for the wild-type allele, while 22.4 and 2.7% were heterozygous and homozygous for the mutant allele, respectively. Additional studies are needed to investigate the relationship between these polymorphisms and disease etiopathogenesis in reference populations.

Study of polymorphic variants of the serotonin 2A receptor gene (5-HT2A) and its possible effects on smoking habits of a population from northeastern Brazil.

Previous studies have revealed a genetic component, including genetic polymorphisms in the serotonergic pathway, particularly in the serotonin receptor gene (5-HT2A). The aim of this study was to investigate associations of the T102C (rs6313) and A-1438G (rs6311) polymorphisms with tobacco use in a population from northeastern Brazil. We evaluated these polymorphisms in 135 nonsmokers and 135 smokers using polymerase chain reaction-restricted fragment length polymorphism. The distribution of allele and genotype frequencies and associations of polymorphisms with smoking were assessed with the chi-squared (χ(2)) test, the Fisher exact test, and odds ratio (OR) with a 95% confidence interval (CI). There were no differences in the distribution of genotype and allele frequencies between nonsmokers and smokers for A-1438G (P = 0.80) and T102C (P = 0.35). However, these polymorphisms were significantly associated with habit frequency (A/G: P = 0.02, OR = 6.87, 95%CI = 1.23-38.31, P = 0.04; A/G+G/G: P = 0.04, OR = 3.67, 95%CI = 1.06-12.75, P = 0.07), age of onset (C/C: P = 0.02, OR = 3.26, 95%CI = 1.17-9.07, P = 0.03, and nicotine dependence level (A/G: P = 0.02, OR = 3.28, 95%CI = 1.17-9.18, P = 0.04; A/G+G/G: P = 0.04, OR = 2.81, 95%CI = 1.13-6.99, P = 0.04; T/C: P = 0.03, OR = 3.12, 95%CI = 1.13-8.57, P = 0.04; T/C+C/C: P = 0.02, OR = 3.06, 95%CI = 1.22-7.70, P = 0.02). Therefore, these polymorphisms may not contribute significantly to smoking initiation, they do appear to be associated with habit maintenance.

Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil.

Approximately 200 million people suffer from type 2 diabetes (T2D) worldwide, and the rapid increase in the prevalence of this disease is likely a result of multiple environmental factors, such as increased food intake and decreased physical activity in genetically predisposed individuals. Different population studies have demonstrated a strong association of two polymorphic variations in the TCF7L2 gene, the noncoding single nucleotide polymorphisms (SNPs) rs7903146 (C/T) and rs12255372 (G/T), with T2D. Herein, we analyzed the association of these SNPs with T2D in a population from northeastern Brazil. Our results showed that the genotype and allele frequencies in TCF7L2 rs7903146 and rs12255372 were similar in the patient and control groups (P > 0.05). In addition, the allele frequencies were not significantly associated with T2D risk [rs7903146: odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.52-1.76, P = 1.00, and rs12255372: OR = 1.38, 95%CI = 0.72-2.62, P = 0.41]. These data suggest that the TCF7L2 SNPs rs7903146 and rs12255372 may not significantly contribute to T2D susceptibility in this population. However, our results may reflect the small number of subjects. Alternatively, these results may be attributable to specific ethnic effects, as most of the previously reported associations were demonstrated with predominantly European populations. To reach a definitive conclusion on the role of such gene variants for T2D in mixed populations, additional efforts are necessary to replicate this study with larger populations from areas with more ethnic heterogeneity.

Prevalence of variants that confer risk for venous thromboembolism in an elderly population of northeastern Brazil.

Venous thromboembolism (VTE) is an important cause of morbidity and mortality stemming from cardiovascular disease. It is a multifactorial disease caused by a combination of acquired risk factors, of which advanced age is the most significant, and genetic factors, including the variants FV G1691A, FII G20210A, and MTHFR C677T. We estimated the prevalence of these genomic variants in an elderly population of northeastern Brazil. The study included 188 elderly persons (65-93 years), of which 68 (36.2%) were men and 120 (63.8%) were women. Variants were detected by polymerase chain reaction-restriction fragment length polymorphism analysis, and subsequent electrophoresis on an 8% polyacrylamide gel stained with silver nitrate. The study population was in Hardy-Weinberg equilibrium for the 3 loci. Of the individuals analyzed, none carried variants of FV or FII (0%), and 24.7% had the MTHFR C677T polymorphism: 59 subjects (31.4%) were heterozygous (CT) and 17 subjects (9%) were homozygous (TT). Based on the analysis of these particular genes, we conclude that the study population does not present an increased risk for the development of VTE. Faced with a growing aging population worldwide, similar studies in other countries will help in the prevention of VTE in older individuals.

Prognostic value of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms and the susceptibility to gliomas in individuals from Southeast Brazil.

The TP53 tumor suppressor gene codifies a protein responsible for preventing cells with genetic damage from growing and dividing by blocking cell growth or apoptosis pathways. A common single nucleotide polymorphism (SNP) in TP53 codon 72 (Arg72Pro) induces a 15-fold decrease of apoptosis-inducing ability and has been associated with susceptibility to human cancers. Recently, another TP53 SNP at codon 47 (Pro47Ser) was reported to have a low apoptosis-inducing ability; however, there are no association studies between this SNP and cancer. Aiming to study the role of TP53 Pro47Ser and Arg72Pro on glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of these SNPs in 94 gliomas (81 astrocytomas, 8 ependymomas and 5 oligodendrogliomas) and in 100 healthy subjects by the polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square and Fisher exact test comparisons for genotype distributions and allele frequencies did not reveal any significant difference between patients and control groups. Overall and disease-free survivals were calculated by the Kaplan-Meier method, and the log-rank test was used for comparisons, but no significant statistical difference was observed between the two groups. Our data suggest that TP53 Pro47Ser and Arg72Pro SNPs are not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.

Prognostic value of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms and the susceptibility to gliomas in individuals from Southeast Brazil

The TP53 tumor suppressor gene codifies a protein responsible for preventing cells with genetic damage from growing and dividing by blocking cell growth or apoptosis pathways. A common single nucleotide polymorphism (SNP) in TP53 codon 72 (Arg72Pro) induces a 15-fold decrease of apoptosis-inducing ability and has been associated with susceptibility to human cancers. Recently, another TP53 SNP at codon 47 (Pro47Ser) was reported to have a low apoptosis-inducing ability; however, there are no association studies between this SNP and cancer. Aiming to study the role of TP53 Pro47Ser and Arg72Pro on glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of these SNPs in 94 gliomas (81 astrocytomas, 8 ependymomas and 5 oligodendrogliomas) and in 100 healthy subjects by the polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square and Fisher exact test comparisons for genotype distributions and allele frequencies did not reveal any significant difference between patients and control groups. Overall and disease-free survivals were calculated by the Kaplan-Meier method, and the log-rank test was used for comparisons, but no significant statistical difference was observed between the two groups. Our data suggest that TP53 Pro47Ser and Arg72Pro SNPs are not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.

Dynamic sonography of hepatic tumors.

OBJECTIVE: Our objectives were to propose and evaluate a dynamic sonography protocol for the characterization of hepatic tumors. SUBJECTS AND METHODS: The subjects were 107 patients with focal liver lesions that initially had been found on conventional sonograms. The final diagnoses for the lesions were hepatocellular carcinoma in 60 patients, cholangiocellular carcinoma in six, metastatic carcinoma in 24, hemangioma in 10, and focal fat-spared region in seven. The pulse inversion harmonic imaging mode and a galactose-based contrast agent (Levovist) were used. Dynamic sonography was designed to obtain vascular-phase (composed of the arterial phase and the portal phase) images of the focal lesion and liver-parenchymal-phase images of the whole liver in a series obtained after a bolus injection of the contrast agent. RESULTS: If the whole-tumor or mosaic enhancement patterns (arterial phase) and/or the reticular enhancement (parenchymal phase) are regarded as positive findings for hepatocellular carcinoma, the sensitivity, specificity, and positive predictive value of dynamic sonography in our study were 92%, 96%, and 96%, respectively. If a ring enhancement (arterial to portal phase) or a clear defect (parenchymal phase) or both are regarded as positive findings for cholangiocellular carcinoma or metastasis, the sensitivity, specificity, and positive predictive value were 90%, 95%, and 88%, respectively. If puddle enhancement (portal phase) is regarded as a positive finding for hemangioma, the figures for sensitivity, specificity, and positive predictive value were 60%, 100%, and 100%, respectively. Also, the tumors that showed no focal sign in the liver parenchymal phase were all benign lesions, such as hemangiomas or focal fat-spared regions. CONCLUSION: Dynamic sonography in a protocol combining pulse inversion harmonic imaging and an IV bolus injection of the contrast agent proved to be an effective tool in characterizing liver tumors.

Improvement of an impaired chemiluminescence response to formyl-methionyl-leucyl-phenylalanine in neutrophils from patients with non insulin dependent diabetes mellitus by recombinant human granulocyte-colony stimulating factor.

To explore the possibility that b type recombinant human granulocyte-colony stimulating factor (rhG-CSF) is a useful drug to prevent the morbidity and mortality caused by infections in diabetic patients, we have studied effects of rhG-CSF on chemiluminescence amplified by a luciferin analog (CLA-DCL) and luminol (L-DCL) in response to formyl-Methionyl-Leucyl-Phenylalanine (fMLP) in neutrophils from patients with non insulin dependent diabetes mellitus (NIDDM) (diabetic neutrophils) and healthy subjects (control neutrophils). Both CLA-DCL and L-DCL in diabetic neutrophils were significantly reduced, and L-DCL was more sensitive to this suppression than CLA-DCL. RhG-CSF did not change the basal chemiluminescence in control and diabetic neutrophils, but it primed CLA-DCL and L-DCL. Although, in diabetic neutrophils, the priming effect of rhG-GSF on both CLA-DCL and L-DCL was less compared to that in control neutrophils, L-DCL was more sensitive to this priming effect than CLA-DCL. Because bacterial infection is still an important cause of the morbidity and mortality in diabetic patients, these data suggest that rhG-CSF is a useful drug to prevent the aggravation of bacterial infection in patients with NIDDM.

[Contrast enhanced color Doppler sonogram of liver tumors: a color-filled pattern in the late phase].

In the present report, a "color-filled pattern", the late phase effect in the intra-venous contrast enhanced color Doppler sonography is introduced, using SH/TA-508 as the contrast agent. This pattern is defined as an image of a tumor area filled with color in contrast to the surrounding liver. After contrast enhancement, the detectability of a "feeding artery" increased. And also "color filled pattern" appeared in 14 of the 21 hepatocellular carcinomas but none of the nine other liver tumors. In conclusion, contrast enhancement increases the detectability of a "feeding artery" and improves the sensitivity for HCC with color Doppler sonography. A "color-filled pattern" is also effective in the diagnosis of HCC because it requires no technical skill and shows high specificity.

Value of contrast-enhanced color Doppler sonography in diagnosing hepatocellular carcinoma with special attention to the "color-filled pattern".

PURPOSE: The purpose of this study is to evaluate the effectiveness of contrast-enhanced color Doppler sonography in the diagnosis of hepatocellular carcinoma (HCC), with special attention to the value of a "color-filled pattern." METHODS: Contrast enhancement with Levovist was performed on 30 liver tumors, including 21 HCCs, as part of phase II and III clinical trials. Detection of a "feeding artery" or a "color-filled pattern" with color Doppler sonography was interpreted as a positive finding for HCC. Angiography was also performed. RESULTS: A feeding artery was detected in 9 HCCs before contrast enhancement and 20 HCCs after. A color-filled pattern was seen in 14 HCCs after enhancement. A feeding artery was seen in only 1 non-HCC tumor, and a color-filled pattern was not seen in any non-HCC. The sensitivity and specificity of a feeding artery for the diagnosis of HCC were 95% and 89%, values similar to those of hepatic angiography. The sensitivity and specificity of a color-filled pattern were 67% and 100%, respectively. CONCLUSIONS: Contrast enhancement increases the detectability of a feeding artery and improves the sensitivity of color Doppler sonography for diagnosing HCC. A color-filled pattern is a highly specific finding in the diagnosis of HCC.

Effectiveness of galactose-based intravenous contrast medium on color Doppler sonography of deeply located hepatocellular carcinoma.

The purpose of this study is to examine the effectiveness of intravenously injectable sonographic contrast medium for color Doppler sonographic diagnosis of deeply located hepatocellular carcinoma. Subjects were 7 hepatocellular carcinomas, an adenomatous hyperplasia and a hemangioma located more than 7 cm below the abdominal surface. Levovist, a galactose-based sonographic contrast medium was injected through median cubital vein as a phase-two clinical study, and the pre- and post-enhanced color Doppler sonographic findings of these lesions were compared. The incidence of the positive findings for hepatocellular carcinoma increased from 29% (2/7) to 86% (6/7) of hepatocellular carcinoma after contrast enhancement. Positive findings were 0% in other cases even after enhancement. Levovist brought a certain improvement in the visualization of the tumor vessel by color Doppler sonography without any noteworthy side effects. Contrast enhancement was useful for the diagnosis of liver lesions suspected to be hepatocellular carcinoma by ordinary sonography, but could not be confirmed by color Doppler sonography.

[Measurement of platelet thromboxane A2/prostaglandin H2 receptor in asthmatic patients].

To evaluate the characteristics of platelet TXA2/PGH2 receptors in patients with bronchial asthma, we performed radiobinding assay of gel-filtrated washed platelets obtained from 15 asthmatic patients and 8 normal adults using [3H]-labeled S-145, a TXA2/PGH2 receptor antagonist, as a radiolinged. Data were evaluated by Schatchard's analysis, and the dissociation constant (Kd), an index of the binding characteristic of receptors, and the maximum number of binding sites (Bmax) were calculated. Venous blood was simultaneously collected and was centrifuged, and platelet-rich plasma was prepared. The platelet aggregation rates induced by various concentrations of U-46619, a TXA2 analogue, were measured by Born's method (nephelometry), and the concentration that induced 50% of the maximum platelet aggregation (EC50) was calculated using a concentration-response curve. The Kd value did not differ between the asthmatic patients and normal controls. Some of the asthmatic patients showed a low EC50 and a high Bmax. EC50 was inversely correlated with Bmax. The number of platelet TXA2/PGH2 receptors was shown to be increased in some asthmatic patients.

[Study on the inhibitory effect of AA-2414 on platelet aggregation and its clinical effect in asthmatic patients].

We previously reported that AA-2414, an eicosanoid receptor antagonist, inhibits platelet aggregation mediated by TXA2/PGH2 receptors in patients with bronchial asthma, but that the inhibitory effects differ among individuals. In this study, we measured the in vitro inhibition rate of platelet aggregation by AA-2414 using U-46619 as an aggregating agent in 22 asthmatic patients and classified them into Group A (showing an inhibition rate of 60% or more) and Group B (showing a rate of less than 60%). Subsequently, AA-2414 tablets (40 mg/day) were orally administered to both groups for 6 weeks, and the clinical effects were compared. A positive correlation was observed between the in vitro U-46619-induced platelet aggregation rate and the inhibition rate of aggregation by AA-2414. At the end of administration, marked inhibition of U-46619-induced platelet aggregation was observed in all patients. However, Group A showed a higher improvement rate of symptoms than Group B. Asthmatic patients can be classified into the groups showing good or poor platelet responses. The response may reflect reactivity to TXA2 in the local airway.

Validation of single-photon emission computed tomography (SPECT) using thallium-201 in patients with lung cancer.

To evaluate the primary site, pulmonary hilar, and mediastinal lesions in patients with lung cancer, thallium-201 using single-photon emission computed tomography (SPECT) was used as a tumor agent. The study population consisted of 7 patients (5 men and 2 women), aged 57 to 82 years (mean 68). Tl-201 tomography imaged positive at the primary site in all patients with lung cancer. The images demonstrated the tumor and/or mediastinal lymph nodes that were greater than 2.0cm. In particular, each tomograms facilitated the identification of the Tl-201 increased uptake in proportion to primary site. The short waiting period after injection with Tl-201 clearly offers a major advantage over alternative tumor imaging agents, such as Ga-67 or radiolabeled monoclonal antibodies. Furthermore, Tl-201 SPECT may be useful to detect the tumor and/or mediastinal lymph nodes in patients with lung cancer.

Assessment of cardiac function using radionuclide techniques--theory, technical considerations and clinical application.

The recent expansion of interventional cardiovascular techniques has stimulated the development of non-invasive cardiac studies, to evaluate the outcome of the interventional therapy. Radionuclide ventriculographic technique provides to quantify global left ventricular systolic/diastolic performance, and evaluate the regional left ventricular wall motion during rest or exercise. This concept was extended from the "bedside" to the ambulatory environment with the description of a battery powered device, the radionuclide ventricular function monitor. To assess the performance of cardiac function using radionuclide ventriculography to that using the ambulatory ventricular function monitor, the systolic and diastolic function were measured at rest in a series of healthy volunteers (n = 10) and in patients with cardiovascular disease (n = 23). Seventeen patients had coronary artery disease (CAD) with prior myocardial infarction, three patients had coronary artery disease, and three patients had dilated cardiomyopathy. The 23 patients manifested a wide variation in LV systolic function. The relationship between the multiple gated acquisition (MUGA)-ejection fraction and the ambulatory ventricular function monitor-ejection fraction correlated well (r = 0.90). As a complement to the radionuclide perfusion studies, cardiac blood pool imaging and radionuclide ventricular function monitoring allow for through non-invasive description of cardiac physiology and function in patients with various cardiac disorders.

[Clinical study on the inhibitory effect of AA-2414 on platelet function in asthmatic patients].

We studied the effect of AA-2414, a TXA2 receptor antagonist, on platelet function in 12 asthmatic patients, 6 males and 6 females, whose mean age was 43.6 years. AA-2414 was orally administered to each patient at 20 mg/day for two weeks and then at 40 mg/day for the following two weeks. Platelet aggregation, plasma concentration of TXB2, and serum concentrations of AA-2414 and its metabolites were measured before and after the administration of each dose. Platelet aggregation induced by U-46619 (an analogue of PGH2), STA2 (a stable analogue of TXA2) and arachidonic acid with the administration of AA-2414 was significantly inhibited. The degree of this inhibition was proportional to the serum level of the drug. Plasma concentration of TXA2 tended to be lowered by administration of AA-2414, but it was not statistically significant. Eight (75.0%) of the 12 patients showed clinical improvement. In the cases where the drug was ineffective, the inhibition of platelet aggregation after administration of AA-2414 was less than in those cases where it was effective. We conclude that AA-2414 might exert its antiplatelet and antiasthmatic effects through antagonism of the TXA2 receptor. Investigation of the response to AA-2414 may be useful in assessing the clinical effect of this compound.

Ectopic posterior lobe of the pituitary gland and intractable nocturnal enuresis in a case with pituitary dwarfism.

An 11 5/12-year-old girl with pituitary dwarfism had intractable nocturnal enuresis. Magnetic resonance imaging revealed pituitary stalk transection and the formation of an ectopic posterior lobe. The results of responses to dehydration, infusion of hyperosmolar NaCl solution, and 1-desamino-8-D-arginine vasopressin showed that the nocturnal enuresis in the present case was due to a partial vasopressin deficiency. We suggest that the ectopic posterior lobe is one cause of nocturnal enuresis.