FTIR study of secondary structure changes in Epidermal Growth Factor by gold nanoparticle conjugation.

Conformation of protein is vital to its function, but may get affected when processing to manufacture products. It is therefore important to understand structural changes during each step of production. In this study, we investigate secondary structure changes in the targeting protein Epidermal Growth Factor (EGF) during synthesis of theranostic bifunctional nanoparticle, devised for Photodynamic therapy of breast cancer. We acquired FTIR spectra of EGF; unconjugated, post treatment with α-lipoic acid, attached to gold nanoparticle, and bound to the bifunctional nanoprobe. We observed decreasing disordered structures and turns, and increasing loops, as the synthesis process progressed. There was an overall increase in ß-sheets in final product compared to pure EGF, but this increase was not linear and fluctuated. Previous crystal structure studies on EGF-EGFR complex have shown loops and ß-sheets to be important in the binding interaction. Since our study found increase in these structures in the final product, no adverse effect on binding function of EGF was expected. This was confirmed by functional assays. Such studies may help modify synthesis procedures, and thus secondary structures of proteins, enabling increased functionality and optimum results.

Efficacy of the trial-based thought record, a new cognitive therapy strategy designed to change core beliefs, in social phobia.

WHAT IS KNOWN AND BACKGROUND: Social anxiety disorder (SAD) often follows a chronic course and is associated with substantial impairment in functioning. Although results from clinical trials clearly establish evidence for efficacy of cognitive behavioural therapy in treating this disorder, up to 50% of patients with SAD show little or no improvement. Thus, new approaches that have promised in improving the efficacy of treatment for SAD are needed. One such approach is the trial-based thought record (TBTR), which targets the restructuring of patients' core beliefs. OBJECTIVE: To determine whether patients receiving TBTR would report fewer symptoms of social anxiety and general psychiatric distress following treatment, relative to conventional cognitive therapy (CCT). METHODS: A two-arm randomized trial comparing TBTR (n = 17) with a set of CCT techniques (n = 19), which included the standard seven-column dysfunctional thought record and the positive data log in SAD patients according to DSM-IV. RESULTS: Scores on many outcome measures decreased significantly across the course of treatment in both groups (P < 0·001), including the Liebowitz Social Anxiety Scale, Fear of Negative Evaluation Scale (FNE), Social Avoidance and Distress Scale (SADS), Beck Anxiety Inventory, and Clinical Global Impression - Improvement. In addition, a one-way ancova, taking baseline values as covariates, showed that TBTR was significantly more efficacious than CCT in reducing the scores of FNE (P = 0·01 at mid-treatment and P = 0·004 at post-treatment), and SADS (P = 0·03 at post-treatment). WHAT IS NEW AND CONCLUSION: This study provides preliminary evidence that TBTR is at least as efficacious as CCT in reducing symptoms of SAD, pointing to the need for additional studies of TBTR in SAD and other psychiatric disorders.

Hippocampal volume in borderline personality disorder with and without comorbid posttraumatic stress disorder: a meta-analysis.

BACKGROUND: Several studies have found a reduction in hippocampal volume in borderline personality disorder (BPD) patients. METHODS: In order to investigate the degree to which comorbid posttraumatic stress disorder (PTSD) could account for reduction in hippocampal volume in these patients, we conducted a systematic review and meta-analysis of studies that compared hippocampal volume in BPD patients with and without PTSD relative to healthy controls. RESULTS: Seven articles, involving 124 patients and 147 controls, were included. We found a statistically significant reduction for the left and right hippocampus. Data from the four studies that discriminated BPD patients with and without PTSD indicate that hippocampal volumes were reduced bilaterally in BPD patients with PTSD, relative to healthy controls, but that results were mixed for BPD patients without PTSD, relative to healthy controls. CONCLUSIONS: Results from this meta-analysis suggest that hippocampal volumes are reduced in patients with BPD, relative to healthy controls, but particularly in cases in which patients are diagnosed with comorbid PTSD.

Treatment of psychosis: 30 years of progress.

BACKGROUND: Thirty years ago, psychiatrists had only a few choices of old neuroleptics available to them, currently defined as conventional or typical antipsychotics, as a result schizophrenics had to suffer the severe extra pyramidal side effects. Nowadays, new treatments are more ambitious, aiming not only to improve psychotic symptoms, but also quality of life and social reinsertion. Our objective is to briefly but critically review the advances in the treatment of schizophrenia with antipsychotics in the past 30 years. We conclude that conventional antipsychotics still have a place when just the cost of treatment, a key factor in poor regions, is considered. The atypical antipsychotic drugs are a class of agents that have become the most widely used to treat a variety of psychoses because of their superiority with regard to extra pyramidal symptoms. We can envisage different therapeutic strategies in the future, each uniquely targeting a different dimension of schizophrenia, be it positive, negative, cognitive or affective symptoms.

[Hepatosplenic schistosomiasis portal hypertension: effect of esophagogastric devascularization with splenectomy on the diameter and mean flow velocity in the portal system (ultra-sonographic Doppler]. / Hipertensão portal por esquistossomose mansônica hepatoesplênica: efeito da desconexão ázigo-portal com esplenectomia no diâmetro e na velocidade média de fluxo do sistema portal (estudo ultra-sonográfico com Doppler).

BACKGROUND: Esophagogastric devascularization with splenectomy has been used for the treatment of upper digestive bleeding due to esophagic varices in hepatoportal mansoni's schistosomic portal hypertension. Nevertheless, early portal thrombosis has hampered this surgical technique (13.3% and 53.2%), compromising the good results on the hemorrhagic side. Supposing that portal circulatory changes, due to the surgical treatment, may play an important role in this kind of complication, our objective was to identify the hemodynamic facilitating factors. Portal hemodynamic aspects, identified by ultra-sonographic Doppler study, from two groups of patients: non-operated upon and splenectomized with esophagogastric devascularization in late post-operatory phase (in excess of 6 moths), with portal hypertension due to mansoni hepatoesplenic portal hypertension and in similar clinical conditions, were compared. METHOD: Fifty eight ambulatorial patients were studied, all had portal hypertension caused by mansoni's hepatosplenic schistosomiasis and previous bouts of digestive bleeding. They were divided in two groups: A--29 followed clinically/endoscopically, and group B--29 previously submitted to esophagogastric devascularization with splenectomy. In all was measured the diameter and mean flow velocity in the portal vein and its right and left branches by ultra-sonographic Doppler study. The results were submitted to statistical analysis for inter- and intra-group comparison. RESULTS: Group A (non-operated): the portal vein diameter was greater than the right and left branches (10.6 +/- 2.9, 8.0 +/- 1.8, 9.1 +/- 2.6 cm), the mean flow velocities in the portal vein and its branches were similar (15.62 +/- 6.17, 14.92 +/- 5.33, 16.12 +/- 4.18 cm/seg). Group B (operated): the diameter and mean flow velocity in all vessels were reduced (8.8 +/- 1.7, 5.2 +/- 1.2, 7.5 +/- 2.2 cm/12.53 +/- 2.60, 8.86 +/- 1.75, 9.69 +/- 3.75 cm/seg). CONCLUSIONS: After esophagogastric devascularization with splenectomy, there was a reduction of the diameter and mean flow velocity in the portal vein, its right and left branches.

Binding of lactoferrin and free secretory component to enterotoxigenic Escherichia coli.

The ability of two glycoproteins of human milk, lactoferrin and free secretory component, to bind to Escherichia coli colonization factors (CFAs) was investigated using immunocytochemistry assays of enriched fimbrial extracts. The results revealed that lactoferrin binds to fimbrial CFA I adhesin but not to CFA II adhesin (CS1 and CS3), while free secretory component interacts with both CFA I and CFA II adhesins. Our data indicate that lactoferrin and free secretory component, which are very abundant proteins of human milk, could play an important role against infant enteric disease by blocking bacterial adhesion.

[Doppler ultrasonography evaluation of paraumbilical vein and portal hypertension]. / Evaluation par échographie-Doppler de la veine para-ombilicale dans l'hypertension portale.

UNLABELLED: Portal hypertension is associated to the development of portosystemic collateral veins, particularly the paraumbilical vein. PURPOSE: To evaluate the biometric and hemodynamic characteristics of the portal vessels related to the presence of a patent paraumbilical vein, in the setting of portal hypertension secondary to hepatosplenic schistosomiasis. METHODS: 75 patients with portal hypertension secondary to hepatosplenic schistosomiasis were evaluated by Doppler US. The patients were studied based on the presence (group B) or not (Group A) of a patent paraumbilical vein. The diameter and blood flow velocity of the portal vessels and of the paraumbilical vein were recorded. RESULTS: The paraumbilical vein was detected in 17.33% of patients. The results showed an increase of the diameter of the main and left portal vessels whenever a patent paraumbilical vein was present (portal vein: A = 1.14 +/- 0.29 cm/B = 1.33 +/- 0.16 cm; left branch: A = 0.95 +/- 0.25 cm/B = 1.30 +/- 0.24 cm). The mean blood flow velocity was also increased in the portal trunk (A = 15.96 +/- 6.17 cm/sec/B = 19.82 +/- 6.26 cm/sec) and in the left portal branch (A = 14.77 +/- 4.29 cm/sec/B = 19.92 +/- 6.88 cm/sec). CONCLUSION: The presence of a patent paraumbilical vein is related to significant biometric and hemodynamic variations in the portal venous system, in the setting of portal hypertension secondary to hepatosplenic schistosomiasis.

[Patent paraumbilical vein: hemodynamic importance in Mansoni's hepatosplenic portal hypertension (Study with ultrasonography Doppler]. / Veia paraumbilical pérvia: importância hemodinâmica na hipertensão portal por esquistossomose mansônica hepatoesplênica. (Estudo com ultra-sonografia Doppler).

BACKGROUND: The hemodynamical effect of the collateral portosystemic circulation upon the portal system has not yet been fully understood. The US-Doppler made possible the non-invasive study of the portal system by evaluating the parameters: flow direction, diameter and flow velocity in it's vessels. AIMS: To study the paraumbilical vein as a collateral portosystemic pathway and identify patterns for appraising its hemodynamic importance to the portal system. METHOD: US-Doppler study of the portal system of 24 patients with Mansoni's hepatosplenic schistosomic portal hypertension, previous esophagic variceal bleeding and patent paraumbilical vein with hepatofugal flow. The diameter and the mean flow velocity were measured in the paraumbilical vein and so were the mean flow velocity in the portal vein, right and left portal branches. The Pearson test (linear correlation) was applied to the portal vein's mean flow velocity and the paraumbilical vein's diameter and mean flow velocity. The patients were divided in four groups: D1-paraumbilical vein with diameter < 0.68 cm (n = 14), D2-paraumbilical vein with diameter > or = 0.68 cm (n = 10), V1-paraumbilical vein with mean flow velocity < 18.41 cm/seg (n = 13) and V2-paraumbilical vein with mean flow velocity > or = 18.41 cm/seg (n = 11). The mean flow velocity in the portal vein, right and left portal branches of the four groups were compared. RESULTS: The paraumbilical vein diameter was 0.68 +/- 0.33 cm (range: 0.15-1.30 cm) and the mean flow velocity was 18.41 +/- 11.51 cm/seg (range: 5.73-38.20 cm/seg). The linear correlation between the portal vein's mean flow velocity/paraumbilical vein diameter and the paraumbilical vein's mean flow velocity showed r = 0.504 and r = 0.735, respectively. In the group D2 there was an increase in the mean flow velocity in the portal vein (17.80 +/- 3.42/22.30 +/- 7.67 cm/seg) and in the left portal branch (16.00 +/- 4.73/22.40 +/- 7.90 cm/seg). In the group V2 there was an increase in the mean flow velocity in the portal vein (16.31 +/- 3.49/21.96 +/- 5.89 cm/seg) and in the left portal branch (14.22 +/- 4.41/21.94 +/- 7.20 cm/seg). There was no change in the right portal branch (13.67 +/- 5.74/15.43 +/- 3.43 cm/seg). CONCLUSIONS: In portal hypertension due to hepatosplenic schistosomiasis, the patent paraumbilical vein, with hepatofugal flow, diameter > or = 0.68 cm and mean flow velocity > or = 18.41 cm/seg causes an increase of the mean flow velocity in the portal vein and left portal branch. The best US-Doppler parameter to appraise the paraumbilical vein influence upon the portal system is the mean flow velocity. The correlation between the increase in portal vein's mean flow velocity is stronger with the paraumbilical vein's mean flow velocity than with its diameter. The increase in the portal vein's and left portal branch's mean flow velocity may be understood as the paraumbilical vein's hemodynamic influence upon the portal system. An active portosystemic collateral pathway increases the mean flow velocity in the vein's segment proximal to its point of origin.

Systematic overview of lithium treatment in acute mania.

OBJECTIVE: To evaluate the efficacy of lithium in the treatment of acute mania. METHOD: Systematic overview of the literature and meta-analysis of randomised controlled trials. Estimation of (i) the differences in the reduction in mania severity scores, and (ii) the ratio and difference in improvement response rates. RESULTS: A total of 658 patients from 12 trials were included. Treatment periods ranged from 3 to 4 weeks. The response rate ratio for lithium against placebo was 1.95 (95%CI 1.17-3.23). The mean number needed to treat was five (95%CI 3-20). Patients were twice as likely to obtain remission with lithium than with chlorpromazine (rate ratio = 1.96, 95%CI 1.02-3.77). The mean number needed to treat was four (95%CI 3-9). Neither carbamazepine nor valproate was more effective than lithium. The response rate ratios were 1.01 (95%CI 0.54-1.88) for lithium compared to carbamazepine and 1.22 (95%CI 0.91-1.64) for lithium against valproate. Haloperidol was no better than lithium on the basis of improvement based on assessment of global severity. The differences in effects between lithium and risperidone were -2.79 (95%CI -4.22 to -1.36) in favour of risperidone with respect to symptom severity improvement and -0.76 (95%CI -1.11 to -0.41) on the basis of reduction in global severity of disease. Symptom and global severity was as well controlled with lithium as with verapamil. Lithium caused more side-effects than placebo and verapamil, but no more than carbamazepine or valproate. CONCLUSION: The clinical trial evidence suggests that lithium should remain the first line treatment for acute mania.

Colour Doppler ultrasound: a new index improves the diagnosis of renal artery stenosis.

The description of a new index, the renal-segmental ratio (RSR), and the comparison of its performance with other conventional Doppler parameters for the detection of renal artery stenosis (RAS). A total of 96 renal units were studied with angiography and colour Doppler ultrasound (US) independently. The Doppler parameters applied were: 1. renal artery peak systolic velocity (RE-PSV), 2. renal-aortic ratio (RAR), 3. early systolic acceleration (ESA), and 4. renal-segmental ratio (RSR). The angiographic study was used as the "gold standard" for the identification of > or = 50% RAS. The results indicate that RSR (sensitivity: 93.33%, specificity: 89.47%) and RE-PSV (sensitivity: 83.33%, specificity: 89.47%) were the best criteria for RAS diagnosis (p values <0.05). The results show that colour Doppler US is a reliable diagnostic modality for RAS diagnosis. The new index (RSR) improves the effectiveness of the method.

Acute sporadic non-A, non-B hepatitis in Northeastern Brazil: etiology and natural history.

In a 4-year follow-up study, patients with acute sporadic non-A, non-B (NANB) hepatitis were evaluated to determine the etiology and natural history of the disease. Acute hepatitis C virus (HCV) was detected in 13 of 43 (30%) of patients, anti-hepatitis E virus (HEV) IgG in 5 (12%), and 25 (58%) were considered non-A-E. The HCV RNA was detected in all HCV patients but none of the non-A-E cases. The initial clinical and biochemical presentation of the HCV and non-A-E cases was quite similar, although 2 of the non-A-E patients had severe disease. The 5 patients who were found to be anti-HEV IgG-reactive recovered within 6 months of follow-up. Of the 13 HCV cases, alanine transaminase (ALT) levels returned to normal in 7 (53. 8%), while 6 (46.2%) continued to show abnormal ALT after 6 months of follow-up. However, 9 (69.2%) of them remained HCV-RNA-positive, denoting virological/biochemical dissociation. Long-term follow-up showed a reappearance of HCV RNA in 2 of the 4 patients who were in virological remission performing 84% of chronicity rate. Acute non-A-E hepatitis patients were less likely to evolve toward chronicity, as compared with acute HCV cases (16% vs. 84%; P =.0001). Only 4 (16%) of the non-A-E patients were hepatitis G virus (HGV)-RNA-positive. Concerning risk factors for acquiring parenterally transmitted viruses, tattooing was the only one that could be associated with HCV transmission (P =.002). No risk factors could be identified for putative non-A-E virus transmission. Liver biopsies performed for chronic HCV patients showed a variable degree of inflammation, while the non-A-E patients presented less severe histological disease.

Antidepressants versus psychotherapy for bulimia nervosa: a systematic review.

OBJECTIVE: To assess the efficacy and acceptability of antidepressants compared to psychotherapy as single approaches for the treatment of bulimia nervosa. METHOD: Dichotomous outcomes were analysed by calculating relative risks and continuous outcomes by calculating effect sizes. The number needed to treat (or harm) was calculated. Methodological quality of trials and heterogeneity in the results were evaluated. RESULTS: A meta-analysis including five randomized controlled trials showed a non-significant difference in short-term remission of bulimic symptoms favouring psychotherapy. Remission rates were 20% for antidepressants and 39% for psychotherapy (P = 0.07). Dropout rates were higher (P = 0.027) for antidepressants (40%) than for psychotherapy (18%). The number needed to harm (NNH) was 4. DISCUSSION: Psychotherapy was superior to antidepressants, but using a more conservative statistical approach this difference, although clinically relevant, was not significant. The number of trials might be insufficient to show the significance of a 20% absolute risk reduction in efficacy. Psychotherapy was a better accepted treatment.

Central lead administration induces natriuretic and kaliuretic effects in rats.

The aim of the present experiments was to discern whether central acute lead injections affect brain control of renal function. Adult Wistar male rats received third-ventricle injections of lead acetate in three different doses (0.03, 0.3, and 3.0 nmol/rat). Lead acetate induced a significant increase in renal excretion of sodium and potassium. Pretreatment with losartan, a selective angiotensin II AT1 receptor antagonist (10.8 nmol/rat into the third ventricle 10 min before central lead injection), inhibits lead-induced natriuretic and kaliuretic effects. In addition, pretreatment with gadolinium, a calcium-channel blocker (0.3 nmol/rat into the third ventricle 20 min before central lead administration), reversed the increase in renal excretion of sodium and potassium provoked by central lead administration. Taken together, the data presented here suggest that lead injected into the third ventricle increases renal excretion of sodium and potassium by a mechanism that depends on the functional integrity of central angiotensin II AT1 receptors and calcium channels.

Role of the spleen on the pathogenesis of schistosomal periportal (pipestem) fibrosis of the liver: an experimental approach.

Splenectomized and sham-operated mice with chronic Schistosoma mansoni infection were compared for the development of periportal fibrosis (pipestem fibrosis). Although this lesion appeared less frequently in splenectomized mice, it also developed in the absence of the spleen. The time of splenectomy, spleen weight, presence of anti-idiotypic antibodies, the number of eggs in the liver, and the type and size of periovular granulomas in the liver as evaluated by computerized morphometry did not show statistically significant differences between the two groups. It is concluded that the role of the spleen in the development of pipestem fibrosis seems ancillary and that multifactorial influences, including worm burden, hepatic vascular adjustment, and factors associated with the biology of extracellular matrix of the liver, probably play a more significant role.

Opiatergic participation in the thirst-inhibiting effect of acute third ventricle injections of cadmium (Cd2+) and lead (Pb2+).

We have previously demonstrated that acute third ventricle injections of both lead and cadmium prevent the dipsogenic response elicited by dehydration or by central injections of dipsogenic agents such as angiotensin II, carbachol and isoproterenol in rats. We have also shown that the antidipsogenic action of cadmium may be due, at least in part, to activation of thirst-inhibitory central serotonergic pathways. In the present paper we show that in Wistar male rats the antidipsogenic effect of both lead acetate (3.0 nmol/rat) and cadmium chloride (3.0 nmol/rat) may be partially dependent on the activation of brain opiatergic pathways since central injections of naloxone (82.5 nmol/rat), a non-selective opioid antagonist, blunt the thirst-inhibiting effect of these metals. One hundred and twenty minutes after the second third ventricle injections, dehydrated animals (14 h overnight) receiving saline + sodium acetate displayed a high water intake (7.90 +/- 0.47 ml/100 g body weight) whereas animals receiving saline + lead acetate drank 3.24 +/- 0.47 ml/100 g body weight. Animals receiving naloxone + lead acetate drank 6.94 +/- 0.60 ml/100 g body weight. Animals receiving saline + saline drank 8.16 +/- 0.66 ml/100 g body weight whilst animals receiving saline + cadmium chloride drank 1.63 +/- 0.37 ml/100 g body weight. Animals receiving naloxone + cadmium chloride drank 8.01 +/- 0.94 ml/100 g body weight. It is suggested that acute third ventricle injections of both lead and cadmium exert their antidipsogenic effect by activating thirst-inhibiting opioid pathways in the brain.

[Atherosclerotic stenosis of the main branches of abdominal aorta. (Prevalence in patients with lower limb occlusive vascular disease)]. / Estenose aterosclerótica dos principais troncos arteriais da aorta abdominal. (Prevalência em pacientes com arteriopatia oclusiva dos membros inferiores).

The authors present the radiographical study of the aortographies of 100 consecutive patients with symptomatic atherosclerotic ischemia of the lower limbs in whom were appraised the stenosis of the celiac trunk, superior mesenteric artery, renal arteries and the presence of the inferior mesenteric artery. The parameters observed were: age, sex, solitary and concomitant stenosis. Seven patients were excluded: six because of arteritis and one because could not be analyzed. Sixty four (68.81%) of the remaining 93 patients had important stenosis (> 30%) of one or more branches of the abdominal aorta, which had a steep raise in number from the 60 decade on. There was no difference regarding to the sex of the patients. The more frequently found solitary stenosis was that of the celiac trunk (16-16.1%) followed by the renal (13-13.0%) and in the concomitant was that of the celiac trunk/renal artery (8-8.6%) and celiac trunk/superior mesenteric artery (5-5.3%). They conclude that in spite of the great number of stenosis of the branches of the abdominal aorta in this kind of patients, there was a low incidence of the concomitant stenosis of the celiac trank/superior mesenteric artery, being difficult to characterize radiologically the digestive ischemic syndrome. They point out that this highly selected group of patients, because of their basic disease, should be more extensively studied in order to identify the results of those vascular stenosis on their digestive tract and orient its eventual treatment.