Is 44-hour better than 24-hour ambulatory blood pressure monitoring in hemodialysis?

The aim of this study is to evaluate if hemodialysis (HD) patients with similar blood pressure (BP) in the whole inter-HD period could have different target organ lesions and survival if the behavior of BP differs from the first to the second day of the inter-HD period. The present study compares 44-hour ambulatory BP monitoring (ABPM) patterns in 45 HD patients. Three BP patterns emerged: group A (n = 15) had similar BPs throughout (138 ± 11/88 ± 12 in the first 22 h vs. 140 ± 11/87 ± 12 mm Hg in the second 22-hour period); group B (n = 15) had a significant systolic BP rise from the first to the second period (132 ± 15/80 ± 12 vs. 147 ± 12/86 ± 13 mm Hg, p < 0.05); group C (n = 15) had significantly higher BPs (p < 0.05) than the other 2 groups throughout the whole inter-HD period, with no significant change between the 2 halves (172 ± 14/108 ± 12 vs. 173 ± 18/109 ± 14 mm Hg). Ventricular mass and survival during the 30-month follow-up period were statistically significantly better in group A, intermediate in group B and worse in group C. The data suggest that a 44-hour ABPM is more accurate than a 24-hour one in evaluating organ lesion and prognosis in HD patients. Copyright © 2006 S. Karger AG.

Inhibition of eukaryotic translation initiation factor 5A (eIF5A) hypusination impairs melanoma growth

The eukaryotic translation initiation factor 5A (eIF5A) undergoes a specific post-translational modification called hypusination. This modification is required for the functionality of this protein. The compound N1-guanyl-1,7-diaminoheptane (GC7) is a potent and selective inhibitor of deoxyhypusine synthase, which catalyses the first step of eIF5A hypusination process. In the present study, the effects of GC7 on cell death were investigated using two cell lines: melan-a murine melanocytes and Tm5 marine melanoma. In vitro treatment with GC7 increased by 3-fold the number of cells presenting DNA fragmentation in Tm5 cells. Exposure to GC7 also decreased viability to both cell lines. This study also describes, for the first time, the in vivo antitumour effect of GC7, as indicated by impaired melanoma growth in C57BL/6 mice. Copyright © 2006 John Wiley & Sons, Ltd.

Inactivation of vesicular stomatitis virus through inhibition of membrane fusion by chemical modification of the viral glycoprotein

Membrane fusion is an essential step in the entry of enveloped viruses into their host cells triggered by conformational changes in viral glycoproteins. We have demonstrated previously that modification of vesicular stomatitis virus (VSV) with diethylpyrocarbonate (DEPC) abolished conformational changes on VSV glycoprotein and the fusion reaction catalyzed by the virus. In the present study, we evaluated whether treatment with DEPC was able to inactivate the virus. Infectivity and viral replication were abolished by viral treatment with 0.5 mM DEPC. Mortality profile and inflammatory response in the central nervous system indicated that G protein modification with DEPC eliminates the ability of the virus to cause disease. In addition, DEPC treatment did not alter the conformational integrity of surface proteins of inactivated VSV as demonstrated by transmission electron microscopy and competitive ELISA. Taken together, our results suggest a potential use of histidine (His) modification to the development of a new process of viral inactivation based on fusion inhibition. © 2006 Elsevier B.V. All rights reserved.

In situ expression of mononuclear cell markers and interleukin-2 receptor in renal allograft biopsies of acute rejection and borderline cases

The correct diagnosis of renal allograft rejection may be difficult using only clinical and/or histopathological criteria. Immunological assays should be considered in order to evaluate the phenotype of inflammatory infiltrate in renal allograft biopsies. Immunohistochemical studies were performed to detect mononuclear cells, CD4 and CD8 T lymphocytes, B lymphocytes, macrophages, null cells, and positive cells for interleukin-2 receptors. A total of 41 allograft biopsies classified into three groups were studied: acute cellular rejection (28 biopsies/22 patients), borderline (7 biopsies/5 patients) and control (6 biopsies/6 patients). In the rejection group (RG), increased cellularity was found mainly at the tubulo-interstitial level. Expression of CD8 positive cells was higher in RG when compared to borderline (BG) and control (CG) groups, respectively (0.9 vs. 0.0 vs. 0.35 cells/mm2; p < 0.001). Expression of macrophages was not statistically significant among the three groups (RG = 0.6 vs. BG = 0.2 vs. CG = 0.0 cells/mm2; p < 0.02). In the BG, CD4 + cells predominated (BG = 0.2 vs. RG = 0.05 vs. CG = 0.0 cells/mm2; p < 0.05). Clinically these patients were treated as cases of acute rejection. The numbers and different types of infiltrating cells did not correlate with patient's clinical outcome. Copyright © Informa Healthcare.

Molecular modeling databases: A new way in the search of protein targets for drug development

DBMODELING is a relational database of annotated comparative protein structure models and their metabolic, pathway characterization. It is focused on enzymes identified in the genomes of Mycobacterium tuberculosis and Xylella fastidiosa. The main goal of the present database is to provide structural models to be used in docking simulations and drug design. However, since the accuracy of structural models is highly dependent on sequence identity between template and target, it is necessary to make clear to the user that only models which show high structural quality should be used in such efforts. Molecular modeling of these genomes generated a database, in which all structural models were built using alignments presenting more than 30% of sequence identity, generating models with medium and high accuracy. All models in the database are publicly accessible at http://www.biocristalografia.df.ibilce.unesp.br/tools. DBMODELING user interface provides users friendly menus, so that all information can be printed in one stop from any web browser. Furthermore, DBMODELING also provides a docking interface, which allows the user to carry out geometric docking simulation, against the molecular models available in the database. There are three other important homology model databases: MODBASE, SWISSMODEL, and GTOP. The main applications of these databases are described in the present article. © 2007 Bentham Science Publishers Ltd.

Amphibian secretions for drug discovery studies: A search for new antiparasitic and antifungal compounds

The antiparasitic and antifungal activities of nine amphibian skin secretions were studied in different in vitro models. Seven secretions presented a considerable antiprotozoan activity and one showed promising results against Candida sp. These results can be the basis for the development of new drugs, especially for neglected parasitic diseases. © 2007 Bentham Science Publishers Ltd.

Shorter CAG repeat in the AR gene is associated with atypical hyperplasia and breast carcinoma

Background: Previous reports into the role of [CAG]n repeat lengths in the androgen receptor (AR) gene indicate that these may play an important part in the development and progression of breast cancer, however, knowledge regarding benign breast lesions is limited. Patients and Methods: PCR-based GeneScan analysis was used to investigate the [CAG]n repeat length at exon 1 of the AR gene in 59 benign breast lesions (27 fibroadenomas, 18 atypical hyperplasias, and 14 hyperplasias without atypia) and 54 ductal breast carcinomas. Seventy-two cancer-free women were used as a control group. In addition, [CAG]n repeats were evaluated for the presence of loss of heterozygosity (LOH) and microsatellite instability (MSI) in a subset of these samples (27 fibroadenomas, 14 hyperplasias without atypia and 22 breast carcinomas). Results: Shorter [CAG]n repeat lengths were strongly correlated with atypical hyperplasias (p=0.0209) and carcinomas (p<0.0001). LOH was found in 1/12 and 4/20 informative cases of hyperplasias without atypia and breast carcinomas, respectively. Three patients with breast carcinoma who had previously presented atypical hyperplasia showed a reduction in the [CAG]n repeat length in their carcinomas. Conclusion: Short [CAG]n repeat length (≤20) polymorphisms are strongly associated with breast carcinomas and atypical hyperplasias. Although non-significant, a subgroup of patients with breast carcinoma and genotype SS showed an association with parameters of worse outcome.

Candida albicans inactivation and cell membrane integrity damage by microwave irradiation

In indicating the microwave irradiation for disinfecting dentures it is necessary to see how this procedure influences Candida albicans integrity and viability. The aim of this study was to evaluate the ability of microwaves to inactivate C. albicans and damage cell membrane integrity. Two 200-ml C. albicans (ATCC 10231) suspensions were obtained. A sterile denture was placed in a beaker containing the Experimental (ES) or the Control suspension (CS). ES was microwaved at 650 W for 6 min. Suspensions were optically counted using methylene blue dye uptake as indicative of membrane-damaged cells; spread on Agar Sabouraud dextrose (ASD) for viability assay; or spectrophotometrically measured at 550 nm. Cell-free solutions were submitted to content analyses of protein (Bradford and Pyrogallol red methods); Ca++ (Cresolftaleine complexone method); DNA (spectrophotometer measurements at 260 nm) and K + (selective electrode technique). Data were analysed by Student's t- or Wilcoxon z-tests (α = 0.05). All ES cells demonstrated cell membrane damage. Viable cells were non-existent in the ES ASD plates. No significant difference in optical density between ES and CS was observed (P = 0.272). ES cells released significantly high protein (P < 0.001, Bradford; P = 0.005, Pyrogallol red), K+ (P < 0.001), Ca++ (P = 0.012) and DNA (P = 0.046) contents. Microwaves inactivated C. albicans and damaged cell membrane integrity. © 2007 The Authors.

Antisperm antibodies in infertile men and their correlation with seminal parameters

Aim: Antisperm antibodies (ASA) in males cause the autoimmune disease 'immune infertility'. The present study intended to detect the presence of ASA and their incidence in men with unexplained infertility, as well as to evaluate the correlation between the presence of ASA and semen parameter alterations. Methods: Blood and sperm assessment were collected to carry out a direct and indirect mixed antiglobulin reaction (MAR) test and semen analysis in infertile and fertile men from the University Hospital of the Faculty of Medicine, Sao Paulo State University, Sao Paulo. Results: In the MARtest, 18.18% of infertile men were positive for ASA. In fertile men, no positivity was found. A significant correlation between the presence of ASA with an increased white blood cell count plus a decreased hypoosmotic swelling test result was observed. Conclusions: The results indicate that ASA are involved in reduced fertility. It is not ASA detection per.se that provides conclusive information about the occurrence of damage to fertility. The correlation between infertility and altered seminal parameters reinforce the ASA participation in this pathology. © 2007 The Authors Journal compilation. © 2007 Japan Society for Reproductive Medicine.

Spontaneous resolution in congenital nasolacrimal obstruction after 12 months

A retrospective observational study was performed in order to evaluate the possibility of spontaneous resolution of tearing in the congenital nasolacrimal obstruction (CNLO). Twenty-seven CNLO child carriers with spontaneous tearing resolution were evaluated according to sex, age of starting and end of symptoms. The data were evaluated by the Chi-Square Test and non-parametric Mann-Whitney test (p ≤ 0.05). Spontaneous resolution occurred between ages 3 and 48 months (Median = 14 months; Mean = 16.2 ± 10.5 months). The period in which the child presented tearing varied from 2 months to 47.5 months (Median = 12 months) and was similar for both sexes, with or without realization of massage. Our data support the possibility of CNLO spontaneous resolution in children beyond 12 months of age, allowing us to suggest postponed probing beyond this time period. Copyright © Informa Healthcare.

Level of insight and clinical features of obsessive-compulsive disorder with and without body dysmorphic disorder

Introduction: Body dysmorphic disorder (BDD) and obsessive-compulsive disorder (OCD) have several similarities and are included among the obsessive-compulsive spectrum of disorders. However, the content of preoccupations and level of insight of BDD patients differ from OCD patients. Objective: To compare the level of insight regarding obsessive-compulsive symptoms (OCS) and other clinical features in OCD patients with and without comorbid BDD. Methods: We evaluated 103 OCD patients (n=25, comorbid BDD), according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria using the Structured Clinical Interview for DSM-IV, the Yale-Brown Obsessive-Compulsive Scale, the University of Sao Paulo Sensory Phenomena Scale, the Beck Depression and Anxiety Inventories, and the Brown Assessment of Beliefs Scale. Resylts: The study groups differed significantly on several clinical features, including level of insight. A worse level of insight regarding OCS was independently associated with the presence of comorbid BDD. Lower educational level, more psychiatric comorbidities, presence of somatic and hoarding obsessions, and presence of intrusive images were associated with BDD comorbidity, even after adjusting for possible confounders. Conclusion: The presence of BDD in OCD patients is associated with poorer insight into obsessional beliefs and higher morbidity, reflected by lower educational levels and higher number of psychiatric comorbid disorders in general.

A comparative study of cytoarchitecture and serotonergic afferents in the suprachiasmatic nucleus of primates (Cebus apella and Callithrix jacchus) and rats (Wistar and Long Evans strains)

The suprachiasmatic nucleus, an essential diencephalic component of the circadian timing system, plays a role in the generation and modulation of behavioral and neuroendocrine rhythms in mammals. Its cytoarchitecture, neurochemical and hodological characteristics have been investigated in various mammalian species, particularly in rodents. In most species, two subdivisions, based on these aspects and considered to reflect functional specialization within the nucleus, can be recognized. Many studies reveal a typical dense innervation by serotonergic fibers in this nucleus, mainly in the ventromedial area, overlapping the retinal afferents. However, a different pattern occurs in certain animals, which lead us to investigate the distribution of serotonergic afferents in the suprachiasmatic nucleus of the Capuchin monkey, Cebus apella, compared to the marmoset, Callithrix jacchus, and two Rattus norvegicus lines (Long Evans and Wistar), and to reported findings for other mammalian species. Our morphometric data show the volume and length of the suprachiasmatic nucleus along the rostrocaudal axis to be greatest in C. apella > C. jacchus > Long Evans ≥ Wistar rats, in agreement with their body sizes. In C. apella, however, the serotonergic terminals occupy only some 10% of the nucleus' area, less than the 25% seen in the marmoset and rats. The distribution of the serotonergic fibers in C. apella does not follow the characteristic ventral organization pattern seen in the rodents. These findings raise questions concerning the intrinsic organization of the nucleus, as well as regarding the functional relationship between serotonergic input and retinal afferents in this diurnal species. © 2007 Elsevier B.V. All rights reserved.

Risk factors for vascular dementia in elderly psychiatric outpatients with preserved cognitive functions

The aim of the study was to assess risk factors for vascular dementia (VaD) in elderly psychiatric outpatients without dementia, and to determine to what extent clinical interventions targeted such risk factors. Out of 250 clinical charts, 78 were selected of patients over 60 years old, who showed no signs of dementia. Information was obtained regarding demographics, clinical conditions (diagnosis according to ICD-10), complementary investigation, cognitive functions (via CAMCOG), neuroimaging, and the presence of risk factors for VaD. Depression was the most prevalent psychiatric disorder (74%). A great majority of the patients (86%) had at least one risk factor for VaD. One-third of the sample showed three or more risk factors for VaD. The clinical conditions related to risk factors for VaD were hypertension (48.7%), heart disease (30.8%), hypercholesterolemia (25.6%), diabetes mellitus (23.1%), stroke (12.8%), tryglyceride (12.8%), and obesity (5.1%). In terms of lifestyle, smoking (19.2%), alcohol abuse (16.7%), and sedentarism (14.1%) were other risk factors found. Definite risk factors for VaD were found in 83.3% of the patients. Previous interventions targeting risk factors were found in only 20% of the cases. The high rates of risk factors for VaD identified in this sample suggest that psychiatrists should be more attentive to these factors for the prevention of VaD. © 2007 Elsevier B.V. All rights reserved.

Role of annexin 1 gene expression in mouse craniofacial bone development

BACKGROUND: Annexin 1 is a 37-kDa protein that has complex intra- and extracellular effects. To discover whether the absence of this protein alters bone development, we monitored this event in the annexin-A1 null mice in comparison with littermate wild-type controls. METHODS: Radiographic and densitometry methods were used for the assessment of bone in annexin-A1 null mice at a gross level. We used whole-skeleton staining, histological analysis, and Western blotting techniques to monitor changes at the tissue and cellular levels. RESULTS: There were no gross differences in the appendicular skeleton between the genotypes, but an anomalous development of the skull was observed in the annexin-A1 null mice. This was characterized in the newborn annexin-A1 null animals by a delayed intramembranous ossification of the skull, incomplete fusion of the interfrontal suture and palatine bone, and the presence of an abnormal suture structure. The annexin-A1 gene was shown to be active in osteocytes during this phase and COX-2 was abundantly expressed in cartilage and bone taken from annexin-A1 null mice. CONCLUSIONS: Expression of the annexin-A1 gene is important for the normal development of the skull in mice, possibly through the regulation of osteoblast differentiation and a secondary effect on the expression of components of the cPLA2-COX-2 system. © 2007 Wiley-Liss, Inc.