Inducible nitric oxide synthase inhibition attenuates lung tissue responsiveness and remodeling in a model of chronic pulmonary inflammation in guinea pigs

We evaluated the influence of iNOS-derived NO on the mechanics, inflammatory, and remodeling process in peripheral lung parenchyma of guinea pigs with chronic pulmonary allergic inflammation. Animals treated or not with 1400W were submitted to seven exposures of ovalbumin in increasing doses. Seventy-two hours after the 7th inhalation, lung strips were suspended in a Krebs organ bath, and tissue resistance and elastance measured at baseline and after ovalbumin challenge. The strips were submitted to histopathological measurements. The ovalbumin-exposed animals showed increased maximal responses of resistance and elastance (p < 0.05), eosinophils counting (p < 0.001), iNOS-positive cells (p < 0.001), collagen and elastic fiber deposition (p < 0.05), actin density (p < 0.05) and 8-iso-PGF2 alpha expression (p < 0.001) in alveolar septa compared to saline-exposed ones. Ovalbumin-exposed animals treated with 1400 W had a significant reduction in lung functional and histopathological findings (p < 0.05). We showed that iNOS-specific inhibition attenuates lung parenchyma constriction, inflammation, and remodeling, suggesting NO-participation in the modulation of the oxidative stress pathway. (C) 2008 Elsevier B.V. All rights reserved.

Benefits of exercise training in diabetic rats persist after three weeks of detraining

Regarding all benefits of exercise training, a question remains: how long are these benefits kept? This study evaluated the effect of 3-week detraining after 10 weeks of training in STZ-diabetic rats. Male Wistar rats were assigned into: sedentary controls, trained controls, trained-detrained controls. sedentary diabetic, trained diabetic and trained-detrained diabetic. Arterial pressure (AP) and heart rate (HR) were recorded by a data acquisition system. Baroreflex sensitivity (BRS) was evaluated by HR responses to AP changes induced by infusion of vasoactive drugs. Intrinsic heart rate (IHR), sympathetic tonus (ST) and vagal tonus (VT) were evaluated by pharmacological blockade with atenolol and atropine. Spectral analysis of systolic AP and HR variabilities (HRV) was performed to estimate autonomic modulation to the heart and vessels. Diabetes cardiovascular and autonomic dysfunctions were reversed by exercise training and partially maintained in the 3-week detraining period. In controls, training decreased AP and HR and improved BRS. changes that returned to baseline values after detraining. IHR and VT were improved in trained diabetic rats and remained in detrained diabetic ones. LF component of HRV decreased in trained control group. In diabetics. exercise training improved variance, and absolute LF and HF components of HRV. Only HF was maintained in detrained diabetic group. Moreover, there was an inverse relationship between plasma glucose and the absolute HF component of HRV. These changes probably determined the different survival rate of 80% in diabetic detrained and 51% in diabetic sedentary rats. (c) 2008 Elsevier B.V. All rights reserved.

Is Chlamydia-infected tubal fimbria the origin of ovarian cancer?

Ovarian cancer is a highly lethal disease and its underlying biology is poorly understood. Prophylactic salpingo-oophorectomies in BRCA + women have recently implicated the fimbria as a site of origin for high-grade serous carcinoma and its intraepithelial precursors. This suggests that at least some ovarian cancers, probably the most aggressive ones, may not originate in the ovary itself, but rather may arise in the uterine tubes. Chronic inflammation is associated with carcinogenesis in several tissues, including liver, esophagogastric junction (cardia), and the uterine cervix. The mechanisms underlying the relationship between inflammation and cancer are complex and involve common pathways, in addition to DNA damage. A critical source of uterine tube inflammation is infection with Chlamydia trachomatis. We hypothesize that C. trachomatis infection may be involved in chronic tubal, inflammation and subsequent fimbrial carcinogenesis. Fimbrial intraepithelial precursors can evolve into high grade serous carcinomas that spread rapidly to the ovarian surface and peritoneum; such tumors may appear to be primary ovarian neoplasia, though in reality being a secondary malignancy. This hypothesis must be further investigated to understand the intracellular signaling pathways involved in Chlamydia infection and its heating, and their relationship to carcinogenesis in order to discover potential therapeutic molecular targets. If our hypothesis were confirmed, salpingectomy instead of ovariectomy may also become the recommended surgery for high risk women. (C) 2008 Elsevier Ltd. All rights reserved.

Dose-dependent hepatic response to subchronic administration of nandrolone decanoate

Background: Androgenic anabolic steroids (AAS) are synthetic hormone derivatives of testosterone and are mainly used to enhance athletic performance and muscle mass, but medical applications also have been described. Short- and long-term side effects have been demonstrated in many organs, but the liver adverse effects are the most common and serious ones associated with AAS use. However, these effects have been supported by few clinical and experimental studies. Objective: To evaluate the hepatic function and structure after 5 wk of nandrolone decanoate administration at three different doses. Methods: Twenty-seven adult male Wistar rats were randomly assigned to the following groups: control, clinical, intermediate, and suprapharmacological doses of nandrolone decanoate during 5 wk. Results: The biochemical studies showed that nandrolone decanoate administration leads to a dose-dependent increase in serum levels of the aspartate aminotransferase (AST) (P < 0.05), alanine aminotransferase (ALT) (P < 0.01), and alkaline phosphatase (ALP) (P < 0.001), as well as a significant decrease in total proteins (P < 0.01), bilirubin (P < 0.05), total cholesterol and fractions (P < 0.05), and triglycerides (P < 0.05). Although a significant statistical difference was found for AST, ALT, and ALP when compared with the control group, their values remained within the normal range. The number of Kupffer cells was increased in the liver parenchyma (P < 0.05), and the content of collagen was increased in the central lobular vein wall, in the hepatic parenchyma, and in the portal space (P < 0.05). Conclusions: These results suggest that subchronic treatment with nandrolone decanoate, mainly administered at higher-than-clinical doses, are potentially deleterious to the liver, leading to incipient fibrosis.

PLUNC protein expression in major salivary glands of HIV-infected patients

Objective: To analyse and compare the expression of Palate, Lung, and Nasal Epithelium Clone (PLUNC) proteins in salivary glands from patients with and without AIDS (control group) using autopsy material. Methods: We analysed the expression of PLUNCs using immunohistochemistry in parotid (n = 45), submandibular (n = 47) and sublingual gland (n = 37) samples of AIDS patients [30 with normal histology, 21 with mycobacteriosis, 14 with cytomegalovirus (CMV) infection, 30 with chronic non-specific sialadenitis, and 30 HIV-negative controls. In situ hybridization (ISH) for SPLUNC 2 in the HIV-negative group was performed. Results: SPLUNC 1 expression was detected in the mucous acini of submandibular and sublingual glands, and SPLUNC 2 were seen in the serous cells. LPLUNC 1 expression was only positive in the salivary ducts. There was a higher expression of SPLUNC 2 in AIDS patients with CMV infection and mycobacteriosis when compared with all other groups. The intensity of staining for SPLUNC 2 was greater around the lesions than the peripheral ones. ISH for SPLUNC 2 showed perinuclear positivity in the serous cells in all HIV-negative cases. Conclusions: SPLUNC 1 and LPLUNC 1 proteins were similarly expressed in the salivary glands of AIDS patients and non-HIV patients. CMV infection and mycobacteriosis increase SPLUNC 2 expression in serous cells in the salivary gland of AIDS patients.

Myocarditis in children and detection of viruses in myocardial tissue: Implications for immunosuppressive therapy

Background: There is scarce information on the potential benefits of immunosuppression in children with myocarditis and viral genomes in myocardium. We investigated the occurrence of myocarditis in children with a preliminary diagnosis of dilated cardiomyopathy, the frequency of cardiotropic viruses in the myocardium, and the response to immunosuppression. Methods: Thirty patients (nine months to 12 years) with left ventricular ejection fraction of 22.8 +/- 4.1% were subjected to right cardiac catheterization and endomyocardial biopsy. Specimens were analyzed for the presence of inflammatory elements (Dallas criteria) and viral genome (polymerase chain reaction). Patients with active myocarditis received immunosuppressants (azatioprine and prednisone) and were recatheterized nine months later. A historical control group of nine patients with myocarditis who did not receive immunosuppressants was included. Results: Active myocarditis was diagnosed in ten patients (five with viral genomes detected). Immunosuppression resulted in a significant increase in left ventricular ejection fraction from 25.2 +/- 2.8% to 45.7 +/- 8.6% (versus 20.0 +/- 4.0% to 22.0 +/- 9.0% in historical controls, p < 0.01) and cardiac index from 3.28 +/- 0.51 L/min/m(2) to 4.40 +/- 0.49 L/min/m(2) (versus 3.50 +/- 0.40 L/min/m(2) to 3.70 +/- 0.50 L/min/m(2) in controls, p < 0.01), regardless of the presence of viral genomes (p - 0.98 and p - 0.22, respectively for the two variables). No relevant clinical events were observed. Non-inflammatory cardiomyopathy was diagnosed in 20 patients (seven with viral genomes). While on conventional therapy, there were four deaths and three assignments to transplantation, and no improvement of left ventricular ejection fraction in the remaining ones (22.5 +/- 3.6% to 27.5 +/- 10.6%). Conclusion: Children with chronic myocarditis seem to benefit from immunosuppressive therapy, regardless of the presence of viral genome in the myocardium. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

(18)F-FDG PET After 2 Cycles of ABVD Predicts Event-Free Survival in Early and Advanced Hodgkin Lymphoma

Our objective was to assess the prognostic value of (18)F-FDG PET after 2 cycles of chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in Hodgkin lymphoma (HL) patients overall and in subgroups of patients with early and advanced stages and with low and high risks according to the International Prognostic Score (IPS). Methods: One hundred fifteen patients with newly diagnosed HL were prospectively included in the study. All underwent standard ABVD therapy followed by consolidation radiotherapy in cases of bulky disease. After 2 cycles of ABVD, the patients were evaluated with PET (PET2). Prognostic analysis compared the 3-y event-free survival (EFS) rate to the PET2 results, clinical data, and IPS. Results: Of the 104 evaluated patients, 93 achieved complete remission after first-line therapy. During a median follow-up of 36 mo, relapse or disease progression was seen in 22 patients. Treatment failure was seen in 16 of the 30 PET2-positive patients and in only 6 of the 74 PET2-negative patients. PET2 was the only significant prognostic factor. The 3-y EFS was 53.4% for PET2-positive patients and 90.5% for PET2-negative ones (P < 0.001). When patients were categorized according to low or high IPS risk and according to early or advanced stage of disease, PET2 was also significantly associated with treatment outcome. Conclusion: PET2 is an accurate and independent predictor of EFS in HL. A negative interim (18)F-FDG PET result is highly predictive of treatment success in overall HL patients, as well as in subgroups with early or advanced-stage disease and with low or high IPS risk.

Conservation of hepatitis C virus nonstructural protein 3 amino acid sequence in viral isolates during liver transplantation

As a consequence of selective pressure exerted by the immune response during hepatitis C virus (HCV) infection, a high rate of nucleotide mutations in the viral genome is observed which leads to the emergence of viral escape mutants. The aim of this study was to evaluate the evolution of the amino acid (aa) sequence of the HCV nonstructural protein 3 (NS3) in viral isolates after liver transplantation. Six patients with HCV-induced liver disease undergoing liver transplantation (LT) were followed up for sequence analysis. Hepatitis C recurrence was observed in all patients after LT. The rate of synonymous (dS) nucleotide substitutions was much higher than that of nonsynonymous (dN) ones in the NS3 encoding region. The high values of the dS/dN ratios suggest no sustained adaptive evolution selection pressure and, therefore, absence of specific NS3 viral populations. Clinical genotype assignments were supported by phylogenetic analysis. Serial samples from each patient showed lower mean nucleotide genetic distance when compared with samples of the same HCV genotype and subtype. The NS3 samples studied had an N-terminal aa sequence with several differences as compared with reference ones, mainly in genotype 1b-infected patients. After LT, as compared with the sequences before, a few reverted aa substitutions and several established aa substitutions were observed at the N-terminal of NS3. Sites described to be involved in important functions of NS3, notably those of the catalytic triad and zinc binding, remained unaltered in terms of aa sequence. Rare or frequent aa substitutions occurred indiscriminately in different positions. Several cytotoxic T lymphocyte epitopes described for HCV were present in our 1b samples. Nevertheless, the deduced secondary structure of the NS3 protease showed a few alterations in samples from genotype 3a patients, but none were seen in 1b cases. Our data, obtained from patients under important selective pressure during LT, show that the NS3 protease remains well conserved, mainly in HCV 3a patients. It reinforces its potential use as an antigenic candidate for further studies aiming at the development of a protective immune response.

Sleep-related changes in hemodynamic and autonomic regulation in human hypertension

Objectives The present study investigates the hemodynamic and autonomic regulation during sleep-awake transitions and across different sleep cycles in patients with essential hypertension. Methods Nineteen individuals free of sleep apnea (10 normotensive and nine hypertensive matched for age, sex, and body mass index) underwent a standard polysomnography, with simultaneous electrocardiography and beat-to-beat blood pressure monitoring (Portapres). All measurements were determined while awake (before and after sleep), as well as in the beginning and at end of the sleep cycle (first/last cycle of nonrapid and rapid eye movement stages). Results Systolic blood pressure was higher in hypertensives and exhibited a similar reduction to the normotensives ones in initial nonrapid eye movement sleep. This reduction was because of different mechanisms: a significant fall in cardiac output in normotensives, whereas in hypertensives was also dependent of a decrease in peripheral vascular resistance. Hypertensive patients presented lower heart rate variation and attenuated baroreflex sensitivity during sleep but not immediately before and after sleep. Spectral analysis suggested a higher sympathetic activity in the sleep stages in hypertension. Additionally, a progressive sympathetic predominance (final rapid eye movement> initial rapid eye movement and awake period postsleep> awake period presleep) was observed in both groups. Conclusion Hypertension is associated with depressed baroreflex sensitivity and increased sympathetic activation during sleep. The greater sympathetic predominance at the end of night (preceding the morning surge of sympathetic activity) could be implicated in the occurrence of cardiovascular events. J Hypertens 27: 1655-1663 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Evolution of Laparoscopic Colorectal Surgery in Brazil Results of 4744 Patients From the National Registry

Background: Since its introduction, laparoscopic colorectal surgery has raised intense debate and controversies regarding its safety and effectiveness. Methods: This multicentric registry reports the experience of 28 Brazilian surgical teams specializing in laparoscopic colorectal surgery. Results: Between 1992 and 2007, 4744 patients (1994 men-42% and 2750 women-58%) were operated upon, with ages ranging from 13 to 94 years (average 57.5y). Benign diseases were diagnosed in 2356 patients (49.6%). Most diseases were located in 50.7% of the left and sigmoid colon, 28.2% in the rectum and anal canal. 8.0% in the right colon, and diffuse 7.0%. There were 181 (3.8%) intraoperative complications (from 0% to 14%). There were 261 (5.5%) reported conversions to laparotomy (from 0% to 16.5%), mainly during the early experience (n = 119 - 59.8%). Postoperative complications were registered in 683 (14.5%) patients (from 5.0% to 50%). Mortality occurred in 43 patients (0.8%). Surgeons who performed less than 50 cases reported similar rates of intraoperative (4.2% vs. 3.8%,- P = 0.7), postoperative complications (20.8% vs. 14.3%; P = 0.07), and mortality (1.0% vs. 0.9%; P = 0.5) but the conversion rate was higher (10.4% vs. 5.4%; P = 0.04). Two thousand three hundred and eighty-nine (50.4%) malignant tumors were operated upon, and histologic classification showed 2347 (98%) adenocarcinomas, 30 (0.6%) spinocelular carcinomas, and 12 (0.2%) other histologic types. Tumor recurrence rate was 16.3% among patients followed more than I year. After an average follow-Lip of 52 months, 19 (0.8%) parietal recurrences were reported, 18 of which were in port sites and I in a patient with disseminated disease. There was no incisional recurrence in the ports used to withdraw the pathologic specimen. Compared with other registries, there was a 75% increase in the number of groups pet-forming laparoscopic colorectal surgery and a decrease in conversions (from 10.5%. to 5.5%) and mortality (from 1.5% to 0.9%) rates. Conclusions: (1) The number of patients operated upon increased expressively during the last years; (2) operative indications for benign and malignant diseases were similar, and diverticular disease of the colon comprised 40% of the benign ones; (3) conversion and mortality rates decreased over time; (4) Surgeon`s experience did not influence the complication rates, but was associated with a lower conversion; and (5) oncologic outcome expressed by recurrence rates showed results similar to those reported in conventional surgery.

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

A Simple Technique for Large Tumor Removal During Laparoscopic Liver Resection

Experience with laparoscopic liver resections has increased in recent years, and so have the number of patients operated on by minimally invasive techniques. Specimen extraction is an important step of laparoscopic liver resection. The size of the specimen, is Usually a limitation for the use Of laparoscopy. The aim of this paper is to describe a new technique combining Pfannenstiel suprapubic incision and obstetric forceps to remove a large specimen from laparoscopic liver resections. The present technique allows an expeditious extraction of intact specimens, even huge ones, through a standard suprapubic Pfannenstiel incision. This technique has additional functional and cosmetic advantages over other techniques of specimen retrieval. We believe that the described technique is feasible, can be easily and rapidly performed, and facilitates laparoscopic liver resection by reducing the technical difficulties for specimen removal and may also be used in other abdominal laparoscopic interventions that deal with large surgical specimens.

Comparative effects of wavelengths of low-power laser in regeneration of sciatic nerve in rats following crushing lesion

Peripheral nerves are structures that, when damaged, can result in significant motor and sensory disabilities. Several studies have used therapeutic resources with the aim of promoting early nerve regeneration, such as the use of low-power laser. However, this laser therapy does not represent a consensus regarding the methodology, thus yielding controversial conclusions. The objective of our study was to investigate, by functional evaluation, the comparative effects of low-power laser (660 nm and 830 nm) on sciatic nerve regeneration following crushing injuries. Twenty-seven Wistar rats subjected to sciatic nerve injury were divided into three groups: group sham, consisting of rats undergoing simulated irradiation; a group consisting of rats subjected to gallium-aluminum-arsenide (GaAlAs) laser at 660 nm (10 J/cm(2), 30 mW and 0.06 cm(2) beam), and another one consisting of rats subjected to GaAlAs laser at 830 nm (10 J/cm(2), 30 mW and 0.116 cm(2)). Laser was applied to the lesion for 21 days. A sciatic functional index (SFI) was used for functional evaluation prior to surgery and on days 7, 14, and 21 after surgery. Differences in SFI were found between group 660 nm and the other ones at the 14th day. One can observe that laser application at 660 nm with the parameters and methods utilised was effective in promoting early functional recovery, as indicated by the SFI, over the period evaluated.

MECHANICAL PROPERTIES OF GASTROCNEMIUS ELETROSTIMULATED AFTER IMMOBILIZATION

Introduction: Mechanical properties (MP) are clinically applicable tools for healthcare professionals working on the musculoskeletal system. Objectives: The aim of this study was to evaluate two protocols of neuromuscular electric stimulation (NMES) to improve MP regeneration of the myotendinous complex after segment immobilization in female rats. Materials and Methods: Fifty animals were equally distributed into five groups: Control (CG, n=10); Immobilized (IG, n=10); Immobilized and freely remobilized (IFG, n=10); Immobilized and NMES once/day (IEG1, n=10); Immobilized and MNES twice/day (IEG2, n=10). Immobilization was kept for 14 days, and remobilization was subsequently released for 10 days. NMES was applied for 10 days, post-immobilization, every morning for 10 minutes to IEG1 animals and every morning and afternoon (total 20 minutes) to the IEG2 group. After these procedures, the gastrocnemius muscle was submitted to the mechanical traction assay to evaluate stiffness, resilience, load and stretching at maximum limit MPs. Results: Immobilization reduced the MP values concerning load and stiffness (p 0.05). Results for NMES applied twice a day were less satisfactory than the ones obtained with one application or in the remobilized group (p>0.05). Conclusion: It is concluded that the gastrocnemius muscle became structurally better organized through a single NMES application and by remobilization.

Change in blood flow velocity demonstrated by Doppler ultrasound in upper limb after axillary dissection surgery for the treatment of breast cancer

The aim of this study was to evaluate the arterial and venous blood flow in women who underwent upper limb axillary dissection surgery for the treatment of breast cancer. Sixty women were divided into two groups: group 1 (G1)-30 women who underwent breast surgery with axillary dissection level II or III (55.6 +/- A 8.6 years); group 2 (G2)-control, 30 women with no breast cancer (57.4 +/- A 7.0 years). Blood flow profile was evaluated by a continuous wave ultrasound Doppler device (Nicolet Vascular Versalab SE(A (R))) with an 8 MHz probe. Axillary, brachial arteries and veins, arm circumference, volumes, and the ankle-brachial index (ABI) were examined. Wilcoxon test and Mann-Whitney tests were applied to analyze blood flow velocity intra-group and between G1 and G2, respectively. The G1 results showed no lymphedema and no peripheral arterial disease (ABI > 0.9). Moreover, the mean blood flow velocity of the vessels ipsilateral to the surgery was significantly higher than the contralateral ones for all vessels examined (P < 0.05). The mean velocity of blood flow of the vessels contralateral to surgery was significantly higher than the axillary artery in G2 (P < 0.05). It can be concluded that women who underwent axillary dissection due to breast cancer showed probable stenosis in the arterial and venous axillary and brachial vessels of the upper limb ipsilateral to the surgery, confirmed by the increase of blood flow velocity, and such obstruction might affect the limb contralateral to the operation site.