CO(2) Abdominal Insufflation Decreases Local and Systemic Inflammatory Response in Experimental Acute Pancreatitis

Objectives: Acute pancreatitis (AP) is a serious disease that is amplified by an associated systemic inflammatory response. We investigated the effect of CO(2) pneumoperitoneum on the local and systemic inflammatory response in AP. Methods: Acute pancreatitis was induced in Wistar rats by 5% taurocholate intraductal injection. Carbon dioxide pneumoperitoneum was applied for 30 minutes before the induction of AP. Inflammatory parameters were evaluated in the peritoneum (ascites, cell number, and tumor necrosis factor alpha [TNF-alpha]), serum (amylase, TNF-alpha, interleukin-6 [IL-6], and IL-10), pancreas (myeloperoxidase [MPO] activity, cyclooxygenase 2 and inducible nitric oxide synthase expression, and histological diagnosis), liver, and lung (mitochondria dysfunction and MPO activity). Results: Abdominal insufflation with CO(2) before induction of AP caused a significant decrease in ascites volume, cells, and TNF-alpha in the peritoneal cavity and in serum TNF-alpha and IL-6 but not IL-10 levels. In the pancreas, this treatment reduced MPO activity, acinar and fat necrosis, and the expression of inducible nitric oxide synthase and cyclooxygenase 2. There were no significant differences on serum amylase levels, liver mitochondrial function, and pulmonary MPO between groups. Conclusions: Our data demonstrated that CO(2) pneumoperitoneum reduced pancreatic inflammation and attenuated systemic inflammatory response in AP. This article suggests that CO(2) pneumoperitoneum plays a critical role on the better outcome in patients undergoing laparoscopic pancreatic surgery.

The impact of trauma and post-traumatic stress disorder on the treatment response of patients with obsessive-compulsive disorder

Few case series studies have addressed the issue of treatment response in patients with obsessive-compulsive disorder (OCD) and comorbid post-traumatic stress disorder (PTSD), and there are no prospective studies addressing response to conventional treatment in OCD patients with a history of trauma (HT). The present study aimed to investigate, prospectively, the impact of HT or PTSD on two systematic, first-line treatments for OCD. Two hundred and nineteen non-treatment-resistant OCD outpatients were treated with either group cognitive-behavioral therapy (GCBT n = 147) or monotherapy with a selective serotonin reuptake inhibitor (SSRI n = 72). Presence of HT and PTSD were assessed at intake, as part of a broader clinical and demographical baseline characterization of the sample. Severity and types of OCD symptoms were assessed with the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and the Dimensional YBOCS (DYBOCS), respectively. Depression and anxiety symptoms were measured with the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). Both treatments had 12-week duration. Treatment response was considered as a categorical [35% or greater reduction in baseline YBOCS scores plus a Clinical Global Impression-Improvement rating of better (2) or much better (1)] and continuous variable (absolute number reduction in baseline YBOCS scores). Treatment response was compared between the OCD + HT group versus the OCD without HT group and between the OCD + PTSD group versus the OCD without PTSD group. Parametric and non-parametric tests were used when indicated. Data on HT and PTSD were available for 215 subjects. Thirty-eight subjects (17.67% of the whole sample) had a positive HT (OCD + HT group) and 22 subjects (57.89% of the OCD + HT group and 10.23% of the whole sample) met full DSM-IV criteria for PTSD. The OCD + HT and OCD without HT groups presented similar response to GCBT (60% of responders in the first group and 63% of responders in the second group, p = 1.00). Regarding SSRI treatment, the difference between the response of the OCD + HT (47.4%) and OCD without HT (22.2%) groups was marginally significant (p = 0.07). In addition, the OCD + PTSD group presented a greater treatment response than the OCD without PTSD group when treatment response was considered as a continuous variable (p = 0.01). The age when the first trauma occurred had no impact on treatment response. In terms of specific OCD symptom dimensions, as measured by the DYBOCS, OCD treatment fostered greater reductions for the OCD + PTSD group than for the OCD without PTSD group in the scores of contamination obsessions and cleaning compulsions, collecting and hoarding and miscellaneous obsessions and related compulsions (including illness concerns and mental rituals, among others). The OCD + PTSD group also presented a greater reduction in anxiety scores than the OCD without PTSD group (p = 0.003). The presence of HT or PTSD was not related to a poorer treatment response in this sample of non-treatment-resistant OCD patients. Unexpectedly, OCD patients with PTSD presented a greater magnitude of response when compared with OCD without PTSD patients in specific OCD symptom dimensions. Future studies are needed to clarify if trauma and PTSD have a more significant impact on the onset and clinical expression of OCD than on the conventional treatment for this condition, and whether OCD stemming from trauma would constitute a subtype of OCD with a distinct response to conventional treatment.

Acute inflammatory response secondary to intrapleural administration of two types of talc

Intrapleural instillation of talc has been used in the treatment of recurrent pleural effusions but can, in rare instances, result in respiratory failure. Side-effects seem to be related to composition, size and inflammatory power of talc particles. The aim of this study was to evaluate the inflammatory response to intrapleural injection of talc containing small particles (ST) or talc containing particles of mixed size (MT). 100 rabbits received intrapleural talc, 50 with ST (median 6.41 mu m) and 50 with MT median 21.15 mu m); the control group was composed of 35 rabbits. Cells, lactate dehydrogenase, C-reactive protein (CRIP), interleukin (IL)-8 and vascular endothelial growth factor were evaluated in serum and bronchoalveolar lavage at 6, 24, 48, 72 and 96 h. Lung histology and the presence of talc were also analysed. Statistics were performed using ANOVA and an unpaired t-test. Most of the parameters showed greater levels in the animals injected with talc than in the controls, suggesting a systemic and pulmonary response. Higher serum levels of CRP and IL-8 were observed in the animals injected with ST. Talc particles were observed in both lungs with no differences between groups. Lung cell infiltrate was more evident in the ST group. In conclusion, talc with larger particles should be the preferred choice in clinical practice in order to induce safer pleurodesis.

Physiological Responses to Brain Stimulation During Limbic Surgery: Further Evidence of Anterior Cingulate Modulation of Autonomic Arousal

Background: In view of conflicting neuroimaging results regarding autonomic-specific activity within the anterior cingulate cortex (ACC), we investigated autonomic responses to direct brain stimulation during sterecitactic limbic surgery. Methods: Skin conductance activity and accelerative heart rate responses to multi-voltage stimulation of the ACC (n = 7) and paralimbic subcauclate (n = 5) regions were recorded during bilateral anterior cingulotomy and bilateral subcauclate tractotomy (in patients that had previously received an adequate lesion in the ACC), respectively. Results: Stimulations in both groups were accompanied by increased autonomic arousal. Skin conductance activity was significantly increased during ACC stimulations compared with paralimbic targets at 2 V (2.34 +/- .68 [score in microSiemens +/- SE] vs. .34 +/- .09, p = .013) and 3 V (3.52 +/- .86 vs. 1.12 +/- .37, p = .036), exhibiting a strong ""voltage-response"" relationship between stimulus magnitude and response amplitude (difference from 1 to 3 V = 1.15 +/- .90 vs. 3.52 +/- .86, p = .041). Heart rate response was less indicative of between-group differences. Conclusions: This is the first study of its kind aiming at seeking novel insights into the mechanisms responsible for central autonomic modulation. It supports a concept that interregional interactions account for the coordination of autonomic arousal.

Low doses of silver nitrate induce pleurodesis with a limited systemic response

Background and objective: Both talc and 0.5% silver nitrate have been shown to induce effective pleurodesis. However, acute adverse systemic inflammatory effects have been described with both agents. The aim of this study was to assess in rabbits the systemic effects associated with a new technique of pleurodesis using repeated low doses of 0.1% silver nitrate. Methods: Rabbits were injected intrapleurally through a chest tube with 0.1% silver nitrate at 0, 24 and 48 h. Other groups received a single injection of 0.5% silver nitrate or 400 mg/kg of talc. Blood samples were collected at 24, 48 and 72 h, and at 7 days, and cytological and biochemical measurements were performed. After 28 days, the presence of macroscopic pleural adhesions and microscopic pleural fibrosis in the pleural cavity were evaluated. Results: Both talc and 0.5% silver nitrate caused significant increases in blood neutrophils, serum LDH, IL-8, transforming growth factor-beta and CRP in comparison with control at almost all time points, whereas sequential doses of 0.1% silver nitrate only increased LDH and CRP in the first 24 h and transforming growth factor-beta at all time points. All groups showed efficient pleurodesis, with no differences in pleural adhesions or fibrosis. Conclusions: Sequential doses of 0.1% silver nitrate produced efficient pleurodesis in rabbits, with a low systemic inflammatory response in comparison with 400 mg/kg of talc or 0.5% silver nitrate.

Response to AIDS in Brazil: contributions of social movements and the sanitary reform

This paper briefly outlines how the political scenario and the mobilization of different actors have contributed to the construction of a public health policy in response to the AIDS epidemics in Brazil. Three factors are presented and discussed: the political context of the 1980s, characterized by redemocratization, growth of social movements, and consolidation of the Brazilian health care reform; the socio-cultural context of the 1970s and 1980s, characterized by achievement of individual freedom, which was key to the organization of the AIDS movement; and finally the actions carried out in the international scenario to support the sustainability of the Brazilian domestic policy and the reinforcement of a global response to face the epidemics in lower-middle income economies.

Strength Training Preserves the Bone Mineral Density of Postmenopausal Women Without Hormone Replacement Therapy

Objective: The study was designed to evaluate the effects of strength training (ST) on the bone mineral density (BMD) of postmenopausal women without hormone replacement therapy. Method: Subjects were randomized into untrained (UN) or trained (TR) groups. The TR group exercised three ST sessions per week for 24 weeks, and body composition, muscular strength, and BMD of the lumbar spine and femur neck were evaluated. Results: Body weight, mass index, and fat percentage were lower after 24 weeks only in the TR group (p < .05). SR also improved the one repetition maximum test in 46% and 39% of upper and lower limbs, respectively. The percentage of demineralization was higher in the UN group than in the TR group at the lumbar spine and femoral neck (p < .05). Discussion: Results indicated that 24 weeks of ST improved body composition parameters, increased muscular strength, and preserved BMD in postmenopausal women.

Genes Differentially Expressed in Prolactinomas Responsive and Resistant to Dopamine Agonists

Background/Aims: Prolactin (PRL) secretion and its gene expression are inhibited by dopamine. Prolactinomas are the most common secreting pituitary adenomas, and dopamine agonists (DA) are the first choice for their treatment. However, a subset of patients is resistant to DA. As the mechanisms involved in DA resistance are not fully understood, the aim of this study was to obtain new insights regarding the molecular differences between the prolactinomas that are responsive to DA and those that are resistant. Methods: Tumor tissue samples were collected from 17 patients who harbored prolactinomas, which were classified as responsive or resistant according to their clinical and laboratorial reaction to DA. The expression of 6 genes was evaluated by real-time polymerase chain reaction: dopamine receptor type 2 (DRD 2), nerve growth factor-beta (NGFB) and its receptor (NGFR), estrogen receptor-alpha (ERA), estrogen receptor-beta (ERB) and the pituitary tumor transforming gene (PTTG). Results: Median DRD 2 and NGFR expression in responsive patients was significantly higher than in resistant ones (p = 0.029 and p = 0.020, respectively). Moreover, the expressions of DRD 2 and NGFR were positively correlated with PRL decrease during treatment (r = 0.66, p = 0.005 and r = 0.57, p = 0.044, respectively). Furthermore, ERB expression was positively correlated to PTTG expression (r = 0.68, p = 0.032) and negatively correlated to NGFB expression (r = -0.75, p = 0.02). Conclusions: DRD2 and NGFR expressions are related to the responsiveness of prolactinoma to DA. However, PTTG, ERB and ERA expressions are not. Also ERB, ERA and PTTG expressions did not present a clear correlation to tumor aggressiveness. Furthermore, the response of prolactinomas to DA should be viewed as a spectrum ranging from the most responsive to the most resistant ones. Copyright (c) 2008 S. Karger AG, Basel

Increased Serum IL-1 beta Level in Alzheimer`s Disease and Mild Cognitive Impairment

Background/Aims: Abnormal inflammatory response has been associated to the pathogenesis of Alzheimer`s disease (AD) and may be a marker of an ongoing neurodegenerative process. The aim of this study was to evaluate the serum levels of interleukin-1 beta (IL-1 beta) in patients with mild cognitive impairment (MCI) and AD. Methods: One hundred and sixty-three older adults ( 58 with mild to moderate AD, 74 with MCI and 31 healthy controls) were recruited for this study. Serum IL-1 beta levels were measured by ELISA. Patients with MCI were subcategorized in single-domain amnestic (aMCI), nonamnestic (naMCI), and multiple-domain (mdMCI) subtypes. Results: Patients with AD and MCI ( all subtypes) had a significant increase in serum IL-1 beta levels as compared to controls (p = 0.03). Patients with mdMCI had serum IL-1 beta levels comparable to those with AD, and significantly higher than those observed in aMCI and naMCI ( p = 0.02). Discussion: The present study provides evidence that inflammatory mechanisms, represented by elevated IL-1 beta, are observed in patients with MCI, specifically in those with impairment in multiple cognitive domains. As these patients are at higher risk of conversion to dementia, we propose that an increased serum IL-1 beta level is a stage marker of the ongoing brain neurodegeneration in the continuum between normal ageing and AD. Copyright (C) 2009 S. Karger AG, Basel

Chemokine Receptors Expression on T Cells and Response to HAART Among Chronic HIV-1-Infected Subjects

Chemokines receptors are used by HIV-1 for entry into CD4(+) T cells. The chemokines are capable of inhibiting HIV replication. This study determined the CCR5 and CXCR4 expression on T cells in HIV-1-infected patients treated with HAART. The successfully treated group ( plasma viral load 400 copies/mL), when compared with the failure group ( plasma viral load >400 copies/mL), had higher median CD4+ T cells count ( 583 and 245 cells/mm(3); respectively, p<0.0001). The failure patients had higher numbers and intensity of CCR5 and CXCR4-expressing T cells. Successfully treated patients were able to normalize the co-receptors expression-over on T cells. The viremic group showed higher CCR5 expression on CD4+ T cells and lower number of cells; CCR5 expression was normalized in the aviremic group; the naive group showed lower CCR5 expression and higher numbers of CD4 T cells; all groups showed normal CXCR4 expression compared to healthy controls. These findings may have clinical implications, since down-regulation of these co-receptors could be an adjuvant strategy for anti-HIV treatment.

Differences in the inflammatory response between patients with and those without diabetes mellitus after coronary stenting

Background: Patients with diabetes mellitus who undergo coronary stenting are at increased risk of restenosis. It is known that inflammation plays a crucial role in restenosis. Objective: We assessed the inflammatory response to elective coronary stent implantation (CSI) in stable diabetic and nondiabetic patients. Methods: C-reactive protein (CRP), soluble (s) P-selectin, and soluble intercellular adhesion molecule (sICAM)-1 plasma levels were determined in diabetic (n = 51) and nondiabetic (n = 56) patients before and 48 hours and 4 weeks after bare metal stenting (BMS). Results: Diabetic patients presented significantly higher inflammatory marker levels before and after CSI. Nonetheless, diabetic and nondiabetic patients had postintervention peak of markers attained within 48 hours. At baseline, diabetic and nondiabetic patients presented CRP levels of 5.0 +/- 20.1 (P <= 0.04) and 3.8 +/- 9.4 mu g/ml and, at 48 hours postintervention, 22.0 +/- 20.2 (P = 0.001; P = 0.002) and 12.6 +/- 11.3 (P <= 0.0001) mu g/ml. Regarding sP-selectin, diabetic and nondiabetic patients obtained levels of, at baseline, 182 +/- 118 (P <= 0.04) and 105 +/- 48 ng/ml and, at 48 hours, 455 +/- 290 (P = 0.001; P <= 0.01) and 215 +/- 120 (P <= 0.04) ng/ml. For diabetic and nondiabetic patients, sICAM-1 levels were, at baseline, 248 +/- 98 (P <= 0.04) and 199 +/- 94 ng/ml and, at 48 hours, 601 +/- 201 (P = 0.001; P <= 0.01) and 283 +/- 220 (P = 0.001) ng/ml. At 4 weeks, for all patients, markers returned to preprocedural levels: versus before PCI: *P = 0.001, P <= 0.0001; versus nondiabetic patients: ^#P <= 0.04, P = 0.002, ^UpsilonP <= 0.01. Conclusions: Diabetic and nondiabetic patients exhibited a temporal inflammatory response after an elective BMS. However, diabetic patients present higher preprocedural levels of CRP, sP-selectin, and sICAM-1 and reveal a further exacerbated inflammatory response after intervention. The differences in inflammatory response may have implications in restenosis within these two sets of patients.

The effects of human herpesvirus 8 infection and interferon-gamma response in cutaneous lesions of Kaposi sarcoma differ among human immunodeficiency virus-infected and uninfected individuals

Background Kaposi sarcoma (KS) is associated with human herpesvirus 8 (HHV-8). The cutaneous immune response in this tumour is not well established and a better understanding is necessary. Objectives To evaluate the HHV-8 expression and immune response in cutaneous lesions of classic KS (CKS) and AIDS-associated KS (AIDS-KS). Methods We performed a quantitative immunohistochemical study of cells expressing HHV-8 latency-associated nuclear antigen (LANA), CD4, CD8 and interferon (IFN)-gamma in skin lesions from patients with CKS and AIDS-KS (with or without highly active antiretroviral therapy, HAART). Results CKS showed higher LANA expression compared with AIDS-KS, regardless of HAART. We also found higher LANA expression in nodules compared with patch/plaque lesions. The tissue CD4+ cell proportion was lower in AIDS-KS patients without HAART than in patients with CKS. In CKS lesions, CD4+ and CD8+ cells expressed IFN-gamma, as shown by double immunostaining. AIDS-KS presented low numbers of IFN-gamma-expressing cells. CD8+ cell numbers were similar in all groups, which appeared unrelated to the clinical or epidemiological type of KS. Conclusions. Our quantitative data on the pattern of KS lesions in selected groups of patients, as shown by in situ immune response, demonstrated a CD4+ T-cell involvement associated with IFN-gamma, an environment of immune response-modified human immunodeficiency virus (HIV) infection. In our sample, the promotion of KS in patients without HIV appears to be related to higher HHV-8 load or virulence than in those with AIDS. This higher resistance may be explained by a sustained immune response against this herpesvirus, that is only partially restored but effective after HAART.

High prevalence of pituitary magnetic resonance abnormalities and gene mutations in a cohort of Brazilian children with growth hormone deficiency and response to treatment

Data were retrospectively collected from 69 Brazilian patients (45 boys) with growth hormone deficiency (GHD) who received exogenous growth hormone (GH) for a median duration of 4 years (range 1-13 years). Forty-two patients had multiple pituitary hormone deficiencies and 27 had isolated GHD. Peak GH was <7 ng/ml (IRMA) or <3.2 ng/ml (IFMA) after two stimulation tests.. Therapy was started at median age of 10.0 years (range 2.2-21.6 years), bone age of 5.8 years (0.5-13.5 years) and height standard deviation score -4.4 (range -9.3 to -1.6). MRI revealed pituitary abnormalities in 87% of patients. Homozygous mutations in PROP-1, GHRH-R, GH-1 or HESX-1 genes were found in 12 patients. Mean height velocities were 3.3 pretreatment and 10.3, 7.8, 7.4 and 6.4 cm/yr, respectively, during 1-4 years of treatment with GH. In conclusion, the high prevalence (96%) of genetic and/or pituitary abnormalities probably reflects the stringent diagnostic criteria used, and GH replacement resulted in significant catch-up growth.