Differential calculus and integration of generalized functions over membranes

In this paper we continue the development of the differential calculus started in Aragona et al. (Monatsh. Math. 144: 13-29, 2005). Guided by the so-called sharp topology and the interpretation of Colombeau generalized functions as point functions on generalized point sets, we introduce the notion of membranes and extend the definition of integrals, given in Aragona et al. (Monatsh. Math. 144: 13-29, 2005), to integrals defined on membranes. We use this to prove a generalized version of the Cauchy formula and to obtain the Goursat Theorem for generalized holomorphic functions. A number of results from classical differential and integral calculus, like the inverse and implicit function theorems and Green's theorem, are transferred to the generalized setting. Further, we indicate that solution formulas for transport and wave equations with generalized initial data can be obtained as well.

Whole blood genome-wide gene expression profile in males after prolonged wakefulness and sleep recovery

Pellegrino R, Sunaga DY, Guindalini C, Martins RC, Mazzotti DR, Wei Z, Daye ZJ, Andersen ML, Tufik S. Whole blood genome-wide gene expression profile in males after prolonged wakefulness and sleep recovery. Physiol Genomics 44: 1003-1012, 2012. First published September 4, 2012; doi: 10.1152/physiolgenomics.00058.2012.-Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. Using high-resolution microarrays we evaluated the gene expression profiles of healthy male volunteers who underwent 60 h of prolonged wakefulness (PW) followed by 12 h of sleep recovery (SR). Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (Baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response, as well as diverse immune system responses, such as natural killer pathways including killer cell lectin-like receptors family, as well as granzymes and T-cell receptors, which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was downregulated following PW and upregulated after SR compared with PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC, and CEACAM genes confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.

Using the Hard, Randy, and Rittler Test to Evaluate Color Vision in Capuchins (Cebus libidinosus)

The identification of color vision types in primates is fundamental to understanding the evolution and biological function of color perception. The Hard, Randy, and Rittler (HRR) pseudoisochromatic test categorizes human color vision types successfully. Here we provide an experimental setup to employ HRR in a nonhuman primate, the capuchin (Cebus libidinosus), a platyrrhine with polymorphic color vision. The HRR test consists of plates with a matrix composed of gray circles that vary in size and brightness. Differently colored circles form a geometric shape (X, O, or Delta) that is discriminated visually from the gray background pattern. The ability to identify these shapes determines the type of dyschromatopsy (deficiency in color vision). We tested six capuchins in their own cages under natural sunlight. The subjects chose between two HRR plates in each trial: one with the gray pattern only and the other with a colored shape, presented on the left or right side at random. We presented the test 40 times and calculated the 95 % confidence limits for chance performance based on the binomial test. We also genotyped all subjects for exons 3 and 5 of the X-linked opsin genes. The HRR test diagnosed two subjects as protan dichromats (missing or defective L-cone), three as deutan dichromats (missing or defective M-cone), and one female as trichromat. Genetic analysis supported the behavioral data for all subjects. These findings show that the HRR test can be applied to diagnose color vision in nonhuman primates.

A combined oral contraceptive containing drospirenone changes neither endothelial function nor hemodynamic parameters in healthy young women: a prospective clinical trial

Background: Combined oral contraceptives (COCs) may lead to a rise in cardiovascular disease risk, possibly associated with changes in blood pressure and endothelial function. Study Design: The objective was to evaluate the impact of COC containing 20 mcg of ethinylestradiol (EE) and 3 mg of drospirenone (DRSP) on the arterial endothelial function, systolic and diastolic blood pressure (SBP and DBP, respectively), heart rate (HR), cardiac output (CO) and total peripheral resistance (TPR) of healthy young women. Of the 71 women in the study, 43 were evaluated before the introduction of COC and after 6 months of its use (case group) and 28, COC nonusers, were assessed for the same parameters at the same time interval (control group). Results: No significant changes in endothelium-dependent and endothelium-independent functions or in measures of SBP, DBP, HR, CO and TPR caused by COC use were observed in the case group (p>.05 for all variables) or in the control group. Conclusion: These data suggest COC with 20 mcg EE and 3 mg DRSP does not alter arterial endothelial function or hemodynamic parameters in healthy young women. (C) 2012 Elsevier Inc. All rights reserved.

Tamoxifen Subcellular Localization; Observation of Cell-Specific Cytotoxicity Enhancement by Inhibition of Mitochondrial ETC Complexes I and III

Recently, a nongenomic cytotoxic component of the chemotherapeutic agent tamoxifen (TAM) has been identified that predominantly triggers mitochondrial events. The present study delineates the intracellular fate of TAM and studies its interaction with a spectrum of cell homeostasis modulators primarily relevant to mitochondria. The subcellular localization of TAM was assessed by confocal fluorescence microscopy. The effect of the modulators on TAM cytotoxicity was assessed by standard MTT assays. Our findings show that in estrogen receptor positive MCF7 breast adenocarcinoma cells and DU145 human prostate cancer cells, TAM largely accumulates in the mitochondria and endoplasmic reticulum, but not lysosomes. Our results further demonstrate that in MCF7, but not in DU145 cells, mitochondrial electron transport chain complex I and III inhibitors exacerbate TAM toxicity with an order of potency of myxothiazol = stigmatellin > rotenone > antimycin A, suggesting a cell-specific cytotoxic interplay between mitochondrial complex I and III function and TAM action.

Septin C-Terminal Domain Interactions: Implications for Filament Stability and Assembly

Septins form a conserved family of filament forming GTP binding proteins found in a wide range of eukaryotic cells. They share a common structural architecture consisting of an N-terminal domain, a central GTP binding domain and a C-terminal domain, which is often predicted to adopt a coiled-coil conformation, at least in part. The crystal structure of the human SEPT2/SEPT6/SEPT7 heterocomplex has revealed the importance of the GTP binding domain in filament formation, but surprisingly no electron density was observed for the C-terminal domains and their function remains obscure. The dearth of structural information concerning the C-terminal region has motivated the present study in which the putative C-terminal domains of human SEPT2, SEPT6 and SEPT7 were expressed in E. coli and purified to homogeneity. The thermal stability and secondary structure content of the domains were studied by circular dichroism spectroscopy, and homo- and hetero-interactions were investigated by size exclusion chromatography, chemical cross-linking, analytical ultracentrifugation and surface plasmon resonance. Our results show that SEPT6-C and SEPT7-C are able to form both homo- and heterodimers with a high alpha-helical content in solution. The heterodimer is elongated and considerably more stable than the homodimers, with a K (D) of 15.8 nM. On the other hand, the homodimer SEPT2-C has a much lower affinity, with a K (D) of 4 mu M, and a moderate alpha-helical content. Our findings present the first direct experimental evidence toward better understanding the biophysical properties and coiled-coil pairings of such domains and their potential role in filament assembly and stability.

Weakness of expiratory muscles and pulmonary complications in malnourished patients undergoing upper abdominal surgery

Background and objective: Malnutrition is prevalent in hospitalized patients and causes systemic damage including effects on the respiratory and immune systems, as well as predisposing to infection and increasing postoperative complications and mortality. This study aimed to assess the impact of malnutrition on the rate of postoperative pulmonary complications, respiratory muscle strength and chest wall expansion in patients undergoing elective upper abdominal surgery. Methods: Seventy-five consecutive candidates for upper abdominal surgery (39 in the malnourished group (MNG) and 36 in the control group (CG)) were enrolled in this prospective controlled cohort study. All patients were evaluated for nutritional status, respiratory muscle strength, chest wall expansion and lung function before surgery. Postoperative pulmonary complications (pneumonia, tracheobronchitis, atelectasis and acute respiratory failure) before discharge from hospital were also evaluated. Results: The MNG showed expiratory muscle weakness (MNG 65 +/- 24 vs CG 82 +/- 22 cm H2O; P < 0.001) and decreased chest wall expansion (P < 0.001), whereas inspiratory muscle strength and lung function were preserved (P > 0.05). The MNG also had a higher incidence of postoperative pulmonary complications compared with the CG (31% and 11%, respectively; P = 0.05). In addition, expiratory muscle weakness was correlated with BMI in the MNG (r = 0.43; P < 0.01). The association between malnutrition and expiratory muscle weakness increased the likelihood of postoperative pulmonary complications after upper abdominal surgery (P = 0.02). Conclusions: These results show that malnutrition is associated with weakness of the expiratory muscles, decreased chest wall expansion and increased incidence of pulmonary complications in patients undergoing elective upper abdominal surgery.

N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation

Campos R, Shimizu MH, Volpini RA, de Bragan a AC, Andrade L, Lopes FD, Olivo C, Canale D, Seguro AC. N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 302: L640-L650, 2012. First published January 20, 2012; doi: 10.1152/ajplung.00097.2011.-Sepsis is a common cause of acute kidney injury (AKI) and acute lung injury. Oxidative stress plays as important role in such injury. The aim of this study was to evaluate the effects that the potent antioxidant N-acetylcysteine (NAC) has on renal and pulmonary function in rats with sepsis. Rats, treated or not with NAC (4.8 g/l in drinking water), underwent cecal ligation and puncture (CLP) 2 days after the initiation of NAC treatment, which was maintained throughout the study. At 24 h post-CLP, renal and pulmonary function were studied in four groups: control, control + NAC, CLP, and CLP + NAC. All animals were submitted to low-tidal-volume mechanical ventilation. We evaluated respiratory mechanics, the sodium cotransporters Na-K-2Cl (NKCC1) and the alpha-subunit of the epithelial sodium channel (alpha-ENaC), polymorphonuclear neutrophils, the edema index, oxidative stress (plasma thiobarbituric acid reactive substances and lung tissue 8-isoprostane), and glomerular filtration rate. The CLP rats developed AKI, which was ameliorated in the CLP + NAC rats. Sepsis-induced alterations in respiratory mechanics were also ameliorated by NAC. Edema indexes were lower in the CLP + NAC group, as was the wet-to-dry lung weight ratio. In CLP + NAC rats, alpha-ENaC expression was upregulated, whereas that of NKCC1 was downregulated, although the difference was not significant. In the CLP + NAC group, oxidative stress was significantly lower and survival rates were significantly higher than in the CLP group. The protective effects of NAC (against kidney and lung injury) are likely attributable to the decrease in oxidative stress, suggesting that NAC can be useful in the treatment of sepsis.

Effects of acute physical exercise on executive functions: a comparison between aerobic and strength exercise

The aim of this study was to compare the effects of acute aerobic and strength exercises on selected executive functions. A counterbalanced, crossover, randomized trial was performed. Forty-two healthy women were randomly submitted to three different conditions: (1) aerobic exercise, (2) strength exercise, and (3) control condition. Before and after each condition, executive functions were measured by the Stroop Test and the Trail Making Test. Following the aerobic and strength sessions, the time to complete the Stroop "non-color word" and "color word" condition was lower when compared with that of the control session. The performance in the Trail Making Test was unchanged. In conclusion, both acute aerobic and strength exercises improve the executive functions. Nevertheless, this positive effect seems to be task and executive function dependent.

Trunk, Pelvis, Hip, and Knee Kinematics, Hip Strength, and Gluteal Muscle Activation During a Single-Leg Squat in Males and Females With and Without Patellofemoral Pain Syndrome

STUDY DESIGN: Controlled laboratory study using a cross-sectional design. OBJECTIVES: To determine whether there are any differences between the sexes in trunk, pelvis, hip, and knee kinematics, hip strength, and gluteal muscle activation during the performance of a single-leg squat in individuals with patellofemoral pain syndrome (PFPS) and control participants. BACKGROUND: Though there is a greater incidence of PFPS in females, PFPS is also quite common in males. Trunk kinematics may affect hip and knee function; however, there is a lack of studies of the influence of the trunk in individuals with PFPS. METHODS: Eighty subjects were distributed into 4 groups: females with PFPS, female controls, males with PFPS, and male controls. Trunk, pelvis, hip, and knee kinematics and gluteal muscle activation were evaluated during a single-leg squat. Hip abduction and external rotation eccentric strength was measured on an isokinetic dynamometer. Group differences were assessed using a 2-way multivariate analysis of variance (sex by PFPS status). RESULTS: Compared to controls, subjects with PFPS had greater ipsilateral trunk lean (mean +/- SD, 9.3 degrees +/- 5.30 degrees versus 6.7 degrees +/- 3.0 degrees; P = .012), contralateral pelvic drop (10.3 degrees +/- 4.7 degrees versus 7.4 degrees 3.8 degrees; P = .003), hip adduction (14.8 degrees +/- 7.8 degrees versus 10.8 degrees +/- 5.6 degrees; P<.0001), and knee abduction (9.2 degrees +/- 5.0 degrees versus 5.8 degrees +/- 3.4 degrees; P<.0001) when performing a single-leg squat. Subjects with PFPS also had 18% less hip abduction and 17% less hip external rotation strength. Compared to female controls, females with PFPS had more hip internal rotation (P<.05) and less muscle activation of the gluteus medius (P = .017) during the single-leg squat. CONCLUSION: Despite many similarities in findings for males and females with PFPS, there may be specific sex differences that warrant consideration in future studies and when clinically evaluating and treating females with PFPS. J Orthop Sports Phys Ther 2012;42(6):491-501, Epub 8 March 2012. doi:10.2519/jospt.2012.3987

Physical Activity In Daily Life In Brazilian COPD Patients During and After Exacerbation

Background: Although hospitalization is recognized as an important cause of reduction in physical activity in daily life (PADL) in COPD, there is only one study evaluating this effect, and it was performed in European COPD patients who have a lower PADL than that of South American COPD patients. Objectives: To investigate the effect of hospitalization due to acute exacerbation of PADL in Brazilian COPD patients and to evaluate the factors that determines the physical activity levels during hospitalization and after discharge. Methods: PADL was quantified using a 3-axis accelerometer on the 3rd day of hospitalization and 1 month after discharge in Brazilian COPD patients who were hospitalized due to disease exacerbation. Six-minute walking distance (6MWD), lower limb strength and pulmonary function were also evaluated. Results: A total of 20 patients completed the study. During hospitalization, patients spent most of the time (87%) lying down or sitting; however, 1 month after they were walking >40 min/day. In addition, patients with prior hospitalization had a lower level of physical activity compared to those without a previous history of hospitalization. The time spent walking during hospitalization was significantly explained by the quadriceps strength (r(2) = 0.29; p < 0.05), while 1 month after, the time spent walking was only significantly explained by the 6MWD (r(2) = 0.51; p = 0.02). Conclusions: Brazilian COPD patients are inactive during hospitalization but become active 1 month after discharge. Previously hospitalized are more inactive both during and after exacerbation. The quadriceps strength and 6MWD explain the physical activity levels during hospitalization and at home, respectively.

Acute heat stress impairs performance parameters and induces mild intestinal enteritis in broiler chickens: Role of acute hypothalamic-pituitary-adrenal axis activation

Studies on the environmental consequences of stress are relevant for economic and animal welfare reasons. We recently reported that long-term heat stressors (31 +/- 1 degrees C and 36 +/- 1 degrees C for 10 h/d) applied to broiler chickens (Gallus gallus domesticus) from d 35 to 42 of life increased serum corticosterone concentrations, decreased performance variables and the macrophage oxidative burst, and produced mild, multifocal acute enteritis. Being cognizant of the relevance of acute heat stress on tropical and subtropical poultry production, we designed the current experiment to analyze, from a neuroimmune perspective, the effects of an acute heat stress (31 +/- 1 degrees C for 10 h on d 35 of life) on serum corticosterone, performance variables, intestinal histology, and peritoneal macrophage activity in chickens. We demonstrated that the acute heat stress increased serum corticosterone concentrations and mortality and decreased food intake, BW gain, and feed conversion (P < 0.05). We did not find changes in the relative weights of the spleen, thymus, and bursa of Fabricius (P > 0.05). Increases in the basal and the Staphylococcus aureus-induced macrophage oxidative bursts and a decrease in the percentage of macrophages performing phagocytosis were also observed. Finally, mild, multifocal acute enteritis, characterized by the increased presence of lymphocytes and plasmocytes within the lamina propria of the jejunum, was also observed. We found that the stress-induced hypothalamic-pituitary-adrenal axis activation was responsible for the negative effects observed on chicken performance and immune function as well as for the changes in the intestinal mucosa. The data presented here corroborate with those presented in other studies in the field of neuroimmunomodulation and open new avenues for the improvement of broiler chicken welfare and production performance.

Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group) were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg) was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg) increased both paw withdrawal latency in response to radiant heat (8.3 +/- 1.1, 12.7 +/- 1.8, 8.4 +/- 0.8, and 11.1 +/- 3.3 s) and mechanical threshold in response to von Frey filaments (459 +/- 82.8, 447.5 +/- 91.7, 320.1 +/- 120, 126.43 +/- 92.8 mN) at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg) blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics.

17 beta-Estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas

Clinical and experimental evidence suggest that estrogens have a major impact on cognition, presenting neurotrophic and neuroprotective actions in regions involved in such function. In opposite, some studies indicate that certain hormone therapy regimens may provoke detrimental effects over female cognitive and neurological function. Therefore, we decided to investigate how estrogen treatment would influence cognition and depression in different ages. For that matter, this study assessed the effects of chronic 17 beta-estradiol treatment over cognition and depressive-like behaviors of young (3 months old), adult (7 months old) and middle-aged (12 months old) reproductive female Wistar rats. These functions were also correlated with alterations in the serotonergic system, as well as hippocampal BDNF. 17 beta-Estradiol treatment did not influence animals' locomotor activity and exploratory behavior, but it was able to improve the performance of adult and middle-aged rats in the Morris water maze, the latter being more responsive to the treatment. Young and adult rats displayed decreased immobility time in the forced swimming test, suggesting an effect of 17 beta-estradiol also over such depressive-like behavior. This same test revealed increased swimming behavior, triggered by serotonergic pathway, in adult rats. Neurochemical evaluations indicated that 17 beta-estradiol treatment was able to increase serotonin turnover rate in the hippocampus of adult rats. Interestingly, estrogen treatment increased BDNF levels from animals of all ages. These findings support the notion that the beneficial effects of 17 beta-estradiol over spatial reference memory and depressive-like behavior are evident only when hormone therapy occurs at early ages and early stages of hormonal decline. (C) 2011 Elsevier B.V. All rights reserved.

Insulin alone or with captopril: effects on signaling pathways (AKT and AMPK) and oxidative balance after ischemia-reperfusion in isolated hearts

Insulin and the inhibition of the reninangiotensin system have independent benefits for ischemiareperfusion injury, but their combination has not been tested. Our aim was to evaluate the effects of insulin+captopril on insulin/angiotensin signaling pathways and cardiac function in the isolated heart subjected to ischemiareperfusion. Isolated hearts were perfused (Langendorff technique) with KrebsHenseleit (KH) buffer for 25 min. Global ischemia was induced (20 min), followed by reperfusion (30 min) with KH (group KH), KH+angiotensin-I (group A), KH+angiotensin-I+captopril (group AC), KH+insulin (group I), KH+insulin+angiotensin-I (group IA), or KH+insulin+angiotensin-I+captopril (group IAC). Group A had a 24% reduction in developed pressure and an increase in end-diastolic pressure vs. baseline, effects that were reverted in groups AC, IA, and IAC. The phosphorylation of protein kinase B (AKT) was higher in groups I and IA vs. groups KH and A. The phosphorylation of AMP-activated protein kinase (AMPK) was similar to 31% higher in groups I, IA, and IAC vs. groups KH, A, and AC. The tert-butyl hydroperoxide (tBOOH)-induced chemiluminescence was lower (similar to 2.2 times) in all groups vs. group KH and was similar to 35% lower in group IA vs. group A. Superoxide dismutase content was lower in groups A, AC, and IAC vs. group KH. Catalase activity was similar to 28% lower in all groups (except group IA) vs. group KH. During reperfusion of the ischemic heart, insulin activates the AKT and AMPK pathways and inhibits the deleterious effects of angiotensin-I perfusion on SOD expression and cardiac function. The addition of captopril does not potentiate these effects.