Antihypertensive activity of redox derivatives of tryptophan

The essential amino acid, tryptophan, has been shown to lower blood pressure in rats when administered orally or intravenously. In order to potentially enhance this action, a brain-targeting chemical delivery system (CDS) approach was applied to this compound. The CDS is based on a dihydropyridine----pyridinium ion redox system, chemically analogous to the naturally occurring NADH----NAD+ system. The dihydropyridine moiety containing carrier is chemically attached to the amino group by an amide-type bonding while the carboxylic acid functionality is esterified to various alcohols. Physicochemical studies of the new derivatives were performed. The determined chromatographic Rm values indicate an increased lipophilicity for the CDSs compared to the parent compound. Oxidation stability studies performed on selected compounds using a ferricyanide-mediated method showed that the CDSs are oxidized to the respective quaternary salt forms. Activity studies performed in deoxycorticosterone acetate induced hypertensive rats, demonstrated that the delivery system for tryptophan reduced blood pressure more efficiently for a longer time than did the parent compound.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.     

Diagnostic value of 24-hour simultaneous EEG and ECG monitoring of patients with heart diseases and atypical consciousness disorders]

In 24 patients with diagnostically not clear, short, recurrent episodes of consciousness disturbances and heart diseases and/or a history of arrhythmia simultaneous 24-hour recording was done of eeg and ecg. In the differential diagnosis epilepsy was considered, especially since in most cases routine eeg records demonstrated slight episodic changes. During 24-hour recording in 8 cases typical episodes of consciousness disturbances developed but in none of them these episodes were associated with arrhythmia which ruled out their cardiogenic origin. In 2 cases EEG recording served for establishing the diagnosis of partial complex seizures, 2 patients had hyperventilation syncope, one had TIA, in the remaining 3 cases absence of eeg and ecg changes during these episodes and coexistence of anxiety neurosis suggested functional origin. So the combined 24-hour eeg+ecg recording made possible establishing of diagnosis in 1/3 of these patients, enabling adequate treatment to be instituted.     

Appearance of esophageal peristalsis in treated idiopathic achalasia

The authors studied 22 patients with severe dysphagia, and follow-up studies showed the appearance of some esophageal peristalsis for the first time in three of these patients after Heller myotomy. Comparison of pre- and postoperative clinical, radiological, and manometric data of these three subjects and the data of the other 19 patients showed no statistically significant differences between the two groups of patients either before or after cardiomyotomy except for the unusual appearance of esophageal peristalsis after surgery. According to these results it is not possible to predict which patients will develop peristalsis after cardiomyotomy. The different motor pattern observed after surgery might suggest the existence of a different pathogenesis underlying the esophageal motor disorders in these two groups of patients.     

Interference of factor V Leiden on protein S activity: evaluation of a new prothrombin time-based assay.

Protein S activity in plasma from factor V Leiden (FVL)-positive patients may be lower than expected. We investigated a new commercially available method for protein S for such interference. Protein S activity was measured for plasmas from 50 individuals with FVL and their results were compared with those obtained for plasmas from 47 sex-matched and age-matched individuals without FVL. We assumed that the median protein S activity value from a relatively large number of individuals with or without FVL would not be significantly different if there is no influence from FVL. The FVL-positive plasmas gave relatively (albeit not significantly) lower protein S levels than FVL-negative plasmas when both were tested undiluted (86 versus 93 IU/dl, P = 0.06). Those differences were reduced (98 versus 102 IU/dl, P = 0.58) when testing was performed on diluted plasmas. Furthermore, the proportion of patients with FVL identified as low-abnormal on the basis of the specific cut-off values (undiluted = 64 U/dl; diluted = 71 IU/dl), which was 8% when testing was performed on undiluted plasmas, was reduced to 4% when testing was performed on diluted plasmas. Conversely, the corresponding proportions of patients without FVL remained unaltered (4.3 versus 4%). In conclusion, these results indicate that the evaluated method is somewhat affected by FVL and that dilution of plasma prior to testing improves specificity. Protein S activity measurement for FVL-positive patients should be performed on diluted plasma and the results interpreted on the basis of the cut-off value specifically determined for diluted plasmas.     

B(2)-receptor modulation of the reactivity to phenylephrine and angiotensin II in the carotid artery of normotensive rats after trandolapril treatment.

This study was designed to study the effects of angiotensin converting enzyme inhibitors (ACEI) following treatment with trandolapril (0.3 mg kg(-1) day(-1)) on carotid arterial responsiveness in normotensive Wistar rats. Carotid arteries were obtained from control or trandolapril-treated animals and mounted in an isolated organ bath. Reactivity to angiotensin II (Ang II), phenylephrine (Phe) and KCl was studied. Agonist concentration-response curves were constructed in either the absence or presence of the endothelium or after incubation with L-NAME (10(-6) M), HOE140 (10(-7) M) or indomethacin (10(-5) M). Trandolapril treatment decreased the Ang II and Phe potencies in carotid arteries, but did not affect the maximal response. The KCl responses (potency and Emax) were similar in both control and trandolapril-treated arteries. The absence of endothelium increased the response to both agonists in control and trandolapril-treated arteries; however, the inhibitory component from the endothelial layer of the Phe response was greater in trandolapril-treated animals than in control animals. The presence of L-NAME or HOE140 abolished the changes in the potency values of trandolapril-treated animals. The presence of indomethacin did not change the effect of trandolapril on the potency values of both agonists. We conclude that trandolapril treatment decreased the carotid arterial reactivity in normotensive rats and that this effect is endothelium-dependent. Furthermore, the involvement of B(2)-receptors and NO production, but not of prostaglandins, is suggested in this mechanism.     

The Relationship Between Temperament and Impulsive Behaviors in Eating Disordered Subjects

To date, few studies have examined the personality characteristics and clinical predictors of impulsive behaviors in eating disorders (ED). The aim of this work was to study the prevalence of a wide range of impulsive behaviors in a sample of 554 ED subjects and to examine the predictors of these behaviors. Subjects were diagnosed according to DSM-IV criteria as having anorexia nervosa restricting type (ANR; n = 183), anorexia nervosa binge eating/purging type (ANBP; n = 65), bulimia nervosa purging type (BNP; n = 244), and bulimia nervosa nonpurging type (BNNP; n = 62). Nine different types of impulsive behaviors were assessed in these groups. About 55% of the whole sample reported at least one type of impulsive behavior, 35% more than one, and about 13% more than three. According to findings, impulsive and multi-impulsive subjects are characterized by the presence of purging behavior and by specific temperamental features such as high levels of novelty seeking and low persistence. The prediction of impulsive behavior is further improved by considering the presence of a history of childhood abuse, maternal psychiatric morbidity, and some specific psychological symptoms such as maturity fears, perfectionism, depression, and obsessive-compulsive symptoms. The presence of impulsive behavior appears to be associated with overall higher levels of psychiatric symptomatology and eating psychopathology, thus indicating that they are an important feature to be considered in the assessment and treatment of ED.     

The diagnostic value of symptoms for the identification of patients with an increased risk of colorectal disease. A criteria-based analysis.

In most textbooks of gastroenterology, diseases with their symptoms are discussed. The exact diagnostic value of these symptoms, however, regarding the differentiation between organic and functional disease, is not mentioned. A criteria-based meta-analysis of the few existing studies in this field was done. From the 14 identified studies, there were two that did not find any significant symptoms. In the other studies the diagnostic value of colonic symptoms showed great variability. Methodological deficiencies in these studies are probably responsible for the latter. The generalization of these results into general practice is not straightforward and needs research in general practice patients.     

Treatment of traumatized primary teeth: a conservative approach

This retrospective study examined some different types of treatment to primary teeth. The aim of this study was to assess the treatment of traumatized primary teeth and the importance of a long-term follow up. Brazilian children in the age group of 1-4 years from a baby clinic took part in the study. Three hundred and fifteen patients suffered some type of traumatic injury, a total of 338 affected teeth. Data were registered in specific records and submitted to statistic analysis. The most prevalent type of treatment was monitor only (85%) followed by tooth extraction and endodontic procedure. Invasive treatments were performed in case of severe traumas, usually 6 months after the injury. We verified that a careful follow up might be the preferential choice to the treatment of traumatic primary teeth even in some severe cases.     

Genome and transcriptome scale portrait of sigma factors in Mycobacterium avium subsp. paratuberculosis.

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne's disease (JD), a chronic gastroenteritis of ruminants and other animals, including primates. Many evidences suggested association of MAP to Crohn's disease, a chronic granulomatous gastrointestinal disease of humans with strong similarities with JD. The present study attempts to evaluate global gene regulation in MAP, which has not been addressed previously, despite the availability of MAP genome sequence. For this purpose, we investigated: (i) the presence of sigma factors and their relationship to sigma factors of other mycobacteria (M. avium subsp.avium, M. tuberculosis, M. bovis, M. leprae and M. smegmatis), and (ii) their expression during different growth conditions and in vitro infection of intestinal epithelial Caco2 cells. MAP genome contains 19 putative sigma factor, but only 12 belong to gene families common to other mycobacteria. Gene expression was evaluated with Real-Time PCR during growth in 7H9 medium and mycobactin J, in 7H9 medium plus mycobactin J and lisozyme, and during infection of Caco2 cells: very different expression patterns were observed and, on the whole, only 7 sigma factors were found to be expressed. sigJ was upregulated during the infection of Caco2 cells. Even if only few sigma factors were expressed in the three conditions tested, the overall high numbers of MAP sigma factors suggests a noteworthy flexibility of this pathogen. Thus, this first report on expression of MAP sigma factors opens the way to an extensive characterization of global gene regulation, as a key to understand strategies of survival and mechanisms of infections used by this organism.