Are tryptase and cathepsin D related toHelicobacter pylori infection and mucosal gastrin in peptic ulcer?

The pathogenesis of peptic ulcer is a complex phenomenon and several factors are thought to be involved in this process. Among others,Helicobacter pylori infection, hypergastrinaemia and some proteases seem to play an essential role in inducing peptic ulceration. We investigated whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (a lysosomal hydrolase which seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked toHelicobacter pylori infection and mucosal content of gastrin. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer and 11 with duodenitis. Tryptase and cathepsin D were measured in mucosal biopsy specimens (body and antrum of the stomach and duodenum) using IRMA methods. Gastrin was assayed in the antral mucosa by means of a RIA method.Helicobacter pylori infection was histologically evaluated (Giemsa). Tryptase and cathepsin D levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. The mucosal content of cathepsin D, but not that of tryptase, was associated withHelicobacter pylori infection. Tryptase, on the other hand, was related to gastrin content. No correlation was found between the two enzymes. It is concluded that tryptase and cathepsin D probably reflect different pathophysiological modifications in ulcer disease. Cathepsin D seems to be mainly related to the phlogistic reaction of the mucosa toHelicobacter pylori infection; tryptase may reflect and indirect link between the action of gastrin and the function of mast cells.     

A double perfusion system with two-channel recording for the simultaneous study of the contractile responses of the circular and longitudinal smooth muscle layers of the rat vas deferens

A device for double perfusion of the vas deferens externally and through the lumen is described in detail. The perfusion system allows the simultaneous recording of drug-induced or spontaneous contractions of the circular and longitudinal smooth muscle layers of the organ. Isometric contractions of the longitudinal (external) layer are recorded through a tension transducer. The contractions of the circular (internal) smooth muscle layer are recorded as changes of the pressure of internal perfusion. Therefore, four different effects can be recorded for a given concentration of agonist by combining the variables related to the route of perfusion (external or internal) and type of muscle (longitudinal or circular). In addition, antagonism or synergism can be studied by simultaneously perfusing a second drug. Results can be expressed as single records or as mean concentration-response curves from which drug-receptor parameters can be directly or indirectly obtained. The importance of employing this method for the analysis of some less usual problems related to the mechanism of drug action is discussed.     

Differential prefrontal gray matter correlates of treatment response to fluoxetine or cognitive-behavioral therapy in obsessive–compulsive disorder

Nearly one-third of patients with obsessive–compulsive disorder (OCD) fail to respond to adequate therapeutic approaches such as serotonin reuptake inhibitors and/or cognitive-behavioral therapy (CBT). This study investigated structural magnetic resonance imaging (MRI) correlates as potential pre-treatment brain markers to predict treatment response in treatment-naïve OCD patients randomized between trials of fluoxetine or CBT. Treatment-naïve OCD patients underwent structural MRI scans before randomization to a 12-week clinical trial of either fluoxetine or group-based CBT. Voxel-based morphometry was used to identify correlations between pretreatment regional gray matter volume and changes in symptom severity on the Yale–Brown Obsessive–Compulsive Scale (Y–BOCS). Brain regional correlations of treatment response differed between treatment groups. Notably, symptom improvement in the fluoxetine treatment group (n=14) was significantly correlated with smaller pretreatment gray matter volume within the right middle lateral orbitofrontal cortex (OFC), whereas symptom improvement in the CBT treatment group (n=15) was significantly correlated with larger pretreatment gray matter volume within the right medial prefrontal cortex (mPFC). No significant a priori regional correlations of treatment response were identified as common between the two treatment groups when considering the entire sample (n=29). These findings suggest that pretreatment gray matter volumes of distinct brain regions within the lateral OFC and mPFC were differentially correlated to treatment response to fluoxetine versus CBT in OCD patients. This study further implicates the mPFC in the fear/anxiety extinction process and stresses the importance of lateral portions of the OFC in mediating fluoxetine's effectiveness in OCD. Clinical registration information: http://clinicaltrials.gov-NCT00680602.     

Gray matter volumes in obsessive-compulsive disorder before and after fluoxetine or cognitive-behavior therapy: a randomized clinical trial

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n=38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n=36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n=26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n=13), whereas no significant GM volume changes were observed in CBT-treated patients (n=13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action.     

Relationship between regional brain volumes and cognitive performance in the healthy aging: an MRI study using voxel-based morphometry

The presence of cognitive impairment is a frequent complaint among elderly individuals in the general population. This study aimed to investigate the relationship between aging-related regional gray matter (rGM) volume changes and cognitive performance in healthy elderly adults. Morphometric magnetic resonance imaging (MRI) measures were acquired in a community-based sample of 170 cognitively-preserved subjects (66 to 75 years). This sample was drawn from the "S?o Paulo Ageing and Health" study, an epidemiological study aimed at investigating the prevalence and risk factors for Alzheimer's disease in a low income region of the city of S?o Paulo. All subjects underwent cognitive testing using a cross-culturally battery validated by the Research Group on Dementia 10/66 as well as the SKT (applied on the day of MRI scanning). Blood genotyping was performed to determine the frequency of the three apolipoprotein E allele variants (APOE ε2/ε3/ε4) in the sample. Voxelwise linear correlation analyses between rGM volumes and cognitive test scores were performed using voxel-based morphometry, including chronological age as covariate. There were significant direct correlations between worse overall cognitive performance and rGM reductions in the right orbitofrontal cortex and parahippocampal gyrus, and also between verbal fluency scores and bilateral parahippocampal gyral volume (p < 0.05, familywise-error corrected for multiple comparisons using small volume correction). When analyses were repeated adding the presence of the APOE ε4 allele as confounding covariate or excluding a minority of APOE ε2 carriers, all findings retained significance. These results indicate that rGM volumes are relevant biomarkers of cognitive deficits in healthy aging individuals, most notably involving temporolimbic regions and the orbitofrontal cortex.     

A population-based morphometric MRI study in patients with first-episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects

Périco CA‐M, Duran FLS, Zanetti MV, Santos LC, Murray RM, Scazufca M, Menezes PR, Busatto GF, Schaufelberger MS. A population‐based morphometric MRI study in patients with first‐episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects.
Bipolar Disord 2011: 13: 28–40. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Many morphometric magnetic resonance imaging (MRI) studies that have investigated the presence of gray matter (GM) volume abnormalities associated with the diagnosis of bipolar disorder (BD) have reported conflicting findings. None of these studies has compared patients with recent‐onset psychotic BD with asymptomatic controls selected from exactly the same environment using epidemiological methods, or has directly contrasted BD patients against subjects with first‐onset psychotic major depressive disorder (MDD). We examined structural brain differences between (i) BD (type I) subjects and MDD subjects with psychotic features in their first contact with the healthcare system in Brazil, and (ii) these two mood disorder groups relative to a sample of geographically matched asymptomatic controls. Methods: A total of 26 BD subjects, 20 subjects with MDD, and 94 healthy controls were examined using either of two identical MRI scanners and acquisition protocols. Diagnoses were based on DSM‐IV criteria and confirmed one year after brain scanning. Image processing was conducted using voxel‐based morphometry. Results: The BD group showed increased volume of the right dorsal anterior cingulate cortex relative to controls, while the MDD subjects exhibited bilateral foci GM deficits in the dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons). Direct comparison between BD and MDD patients showed a focus of GM reduction in the right‐sided dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons) and a trend (p < 0.10, corrected) toward left‐sided GM deficits in the dorsolateral prefrontal cortex of MDD patients. When analyses were repeated with scanner site as a confounding covariate the finding of increased right anterior cingulate volumes in BD patients relative to controls remained statistically significant (p = 0.01, corrected for multiple comparisons). Conclusions: These findings reinforce the view that there are important pathophysiological distinctions between BD and MDD, and indicate that subtle dorsal anterior cingulate abnormalities may be relevant to the pathophysiology of BD.     

Association between major depressive symptoms in heart failure and impaired regional cerebral blood flow in the medial temporal region: a study using 99m Tc-HMPAO single photon emission computerized tomography (SPECT)

BACKGROUND AND PURPOSE: Depressive symptoms are frequently associated with heart failure (HF), but the brain mechanisms underlying such association are unclear. We hypothesized that the presence of major depressive disorder (MDD) emerging after the onset of HF would be associated with regional cerebral blood flow (rCBF) abnormalities in medial temporal regions previously implicated in primary MDD, namely the hippocampus and parahippocampal gyrus. METHOD: Using 99mTc-SPECT, we measured rCBF in 17 elderly MDD-HF patients, 17 non-depressed HF patients, and 18 healthy controls, matched for demographic variables. Group differences were investigated with Statistical Parametric Mapping. RESULTS: Significant rCBF reductions in MDD-HF patients relative to both non-depressed HF patients and healthy controls were detected in the left anterior parahippocampal gyrus and hippocampus (ANOVA, p=0.008 corrected for multiple comparisons) and the right posterior hippocampus and parahippocampal gyrus (p=0.005 corrected). In the overall HF group, there was a negative correlation between the severity of depressive symptoms and rCBF in the right posterior hippocampal/parahippocampal region (p=0.045 corrected). CONCLUSIONS: These findings are consistent with the notion that the medial temporal region is vulnerable to brain perfusion deficits associated with HF, and provide evidence that such functional deficits may be specifically implicated in the pathophysiology of MDD associated with HF.     

Phonemic fluency in Portuguese-speaking subjects in Brazil: ranking of letters

Phonological verbal fluency studies in English most commonly employ the letters F-A-S as stimuli. We assessed the production of words with these and 14 other letters in Portuguese-speaking healthy subjects (n = 74). The letters F-A-S were ranked among the easiest to produce words in one minute, which is consistent with the findings of studies with English-speaking subjects. There were differences in the overall ranking of letters depending on whether the total word number or the latency between words were considered. Our findings provide a databank of phonological verbal fluency performance using different stimuli in Portuguese, and demonstrate that the ranking of the letters F-A-S is comparable between the English and Portuguese languages in terms of the level of difficulty to produce words, when the task is used in its traditional format.