Behavioral profiles displayed by rats in an elevated asymmetric plus-maze: effects of diazepam

When rats are exposed to unknown environments where novelty and fear-inducing characteristics are present (conflictive environments), some specific behaviors are induced and exploration is apparently modulated by fear. In our laboratory, a new type of plus-maze was designed as a model of conflictive exploration. The maze is composed of four arms with different geometrical characteristics, differing from each other by the presence or absence of walls. The degree of asymmetry was as follows: NW, no wall arm; SW, a single high wall present; HL, a low and a high wall present, and HH, two high walls present. The four arms were arranged at 90o angles and the apparatus was called the elevated asymmetric plus-maze (APM). The purpose of the present study was to assess the behavioral profile of rats exposed for a single time to the APM with or without treatment with benzodiazepine. Increasing doses of diazepam were injected intraperitoneally in several groups of male, 90-day-old Holtzman rats. Distilled water was injected in control animals. Thirty minutes after treatment all rats were exposed singly to a 5-min test in the APM. Diazepam induced a biphasic modification of exploration in the NW and SW arms. The increase in the exploration score was evident at low doses of diazepam (0.25-1.0 mg/kg body weight) and the decrease in exploration was found with the higher doses of diazepam (2.0-3.0 mg/kg body weight). Non-exploratory behaviors (permanency) were not affected by benzodiazepine treatment. In the HL arm, exploration was not modified but permanency was increased in a dose-dependent manner. In the HH arm, exploration and permanency were not affected. Results are compatible with the idea that exploration-processing mechanisms in conflictive environments are modulated by fear-processing mechanisms of the brain.

Relation of the disaccharidases in the small intestine of the rat to the degree of experimentally induced iron-deficiency anemia

Hypolactasia associated with severe iron-deficiency anemia has been reported in several studies. The objective of the present study was to determine whether hypolactasia is associated with the degree and duration of iron-deficiency anemia. Newly weaned male Wistar rats were divided into a control group receiving a diet supplemented with iron (C) and an experimental group (E) receiving a diet not supplemented with iron (iron-deficiency diet). The animals were studied on the 3rd, 5th, 7th, 14th, 21st, 28th and 35th days of the experiment, when overall and iron nutritional status and disaccharidase activity in the small intestine were determined by the Dahlqvist method. A reduction in weight occurred in the anemic animals starting on the 5th day of the study. Anemia was present in the experimental animals, with a progressive worsening up to the 14th day (hemoglobin: C = 13.27 and E = 5.37) and stabilizing thereafter. Saccharase and maltase activities did not differ significantly between groups, whereas lactase showed a significant reduction in total (TA) and specific activity (SA) in the anemic animals starting on the 21st day of the study. Median lactase TA for the C and E groups was 2.27 and 1.25 U on the 21st day, 2.87 and 1.88 U on the 28th day, and 4.20 and 1.59 U on the 35th day, respectively. Median lactase SA was 0.31 and 0.20 U/g wet weight on the 21st day, 0.39 and 0.24 U/g wet weight on the 28th day, and 0.42 and 0.23 U/g wet weight on the 35th day, respectively. These findings suggest a relationship between the enzymatic alterations observed and both the degree and duration of the anemic process. Analysis of other studies on intestinal disaccharidases in anemia suggests that the mechanism of these changes may be functional, i.e., that the enterocytes may suffer a reduction in their ability to synthesize these enzymes.

Hyperventilation in panic disorder patients and healthy first-degree relatives

Our aim was to observe the induction of panic attacks by a hyperventilation challenge test in panic disorder patients (DSM-IV) and their healthy first-degree relatives. We randomly selected 25 panic disorder patients, 31 healthy first-degree relatives of probands with panic disorder and 26 normal volunteers with no family history of panic disorder. All patients had no psychotropic drugs for at least one week. They were induced to hyperventilate (30 breaths/min) for 4 min and anxiety scales were applied before and after the test. A total of 44.0% (N = 11) panic disorder patients, 16.1% (N = 5) of first-degree relatives and 11.5% (N = 3) of control subjects had a panic attack after hyperventilating (chi² = 8.93, d.f. = 2, P = 0.011). In this challenge test the panic disorder patients were more sensitive to hyperventilation than first-degree relatives and normal volunteers. Although the hyperventilation test has a low sensitivity, our data suggest that there is no association between a family history of panic disorder and hyperreactivity to an acute hyperventilation challenge test. Perhaps cognitive variables should be considered to play a specific role in this association since symptoms of a panic attack and acute hyperventilation overlap.

Double grade – rakenneputkien puristuskestävyys

Double grade S420MH/S355J2H – rakenneputki on Ruukin kylmämuovattujen rakenneputkien vakioteräslaji. Se voidaan mitoittaa joko lujuusluokan S355 tai S420 mukaisesti. Teräslajin S355 mukaisesti mitoitettaessa on suunnittelu yksinkertaista. Painonsäästöä ja pidennettyjä jännevälejä haluttaessa käytetään lujuusluokan S420 mukaista mitoitusta. Työn tavoitteena oli selvittää kylmämuovattujen teräsrakenneputkien todellinen puristuskestävyys. Eurocode 3:n mukaan kylmämuovatut teräsrakenneputket kuuluvat nurjahduskäyrälle c. Tutkimukseen valittiin viisi eri profiilia olevaa rakenneputkea, joiden poikkileikkausluokat olivat 1, 2, 3 ja 4. Käytettäessä rakenneputkia puristussauvoina, on teräksen käyttö tehokkainta poikkileikkausluokassa 3, lähellä poikkileikkausluokkaa 4. Rakenneputkista laskettiin muunnetun hoikkuuden arvoilla 0.1, 0.5, 1.0 ja 1.5 koesauvojen pituudet kaikille profiileille. Valmistettiin kolme samanlaista koesauvaa jokaisesta koosta ja puristuskokeita suoritettiin yhteensä 57 kappaletta. Koesauvojen todelliset pituudet, alkukäyryydet ja poikkileikkaukset mitattiin. Ainestodistuksista saatiin materiaalin todelliset lujuudet. Laskettiin Eurocode 3:n mukaisesti kestävyydet nurjahduskäyrille a, b ja c. Laskennallisia kestävyyksiä verrattiin puristuskokeiden tuloksiin. Puristuskokeiden tulosten perusteella voidaan b-käyrää pitää oikeana profiileille 100x100x3, 150,150x5 ja 200x200x6. Profiili 150x150x5 kuuluu poikkileikkausluokkaan 2. Profiilit 100x100x3 ja 200x200x6 kuuluvat poikkileikkausluokkaan 4. Profiili 50x50x2 kuuluu nurjahduskäyrälle c. Profiilin poikkileikkausluokka on 1 ja aiemmat tutkimukset tukevat nurjahduskäyrän c käyttöä. Profiilista 300x300x8.8 ei saatu testattua täyttä sarjaa sen suuren kapasiteetin rikottua testilaitteiston, mutta puristuskokeiden perusteella se kuuluu nurjahduskäyrälle b. Profiili kuuluu poikkileikkausluokkaan 4.

Intravenous dipyrone for the acute treatment of episodic tension-type headache: A randomized, placebo-controlled, double-blind study

Acute headaches are responsible for a significant percentage of the case load at primary care units and emergency rooms in Brazil. Dipyrone (metamizol) is easily available in these settings, being the most frequently used drug. We conducted a randomized, placebo-controlled, double-blind study to assess the effect of dipyrone in the acute treatment of episodic tension-type headache. Sixty patients were randomized to receive placebo (intravenous injection of 10 ml saline) or 1 g dipyrone in 10 ml saline. We used seven parameters of analgesic evaluation. The patients receiving dipyrone showed a statistically significant improvement (P<0.05) of pain compared to placebo up to 30 min after drug administration. The therapeutic gain was 30% in 30 min and 40% in 60 min. The number of patients needed to be treated for at least one to have benefit was 3.3 in 30 min and 2.2 in 60 min. There were statistically significant reductions in the recurrence (dipyrone = 25%, placebo = 50%) and use of rescue medication (dipyrone = 20%, placebo = 47.6%) for the dipyrone group. Intravenous dipyrone is an effective drug for the relief of pain in tension-type headache and its use is justified in the emergency room setting.

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH- individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) µU/ml, b) second-phase insulin secretion, 64 (41-86) vs 53 (37-83) µU/ml, and c) ISI, 14.8 (9.0-20.8) vs 16.8 (9.0-27.0) mg kg-1 min-1/µU ml-1. Hepatic insulin extraction in FH+ subjects was similar to that of FH- ones at basal conditions (median, 0.27 vs 0.27 ng/µU) and during glucose infusion (0.15 vs 0.15 ng/µU). Normal glucose-tolerant Brazilian FH+ individuals well-matched with FH- ones did not show defects of insulin secretion, insulin sensitivity, or hepatic insulin extraction as tested by hyperglycemic clamp procedures.

A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid

In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease, 30 patients with body mass indices higher than 25, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyltransferase (gamma-GT) at least more than 1.5 times the upper limit of normality, and hepatic steatosis demonstrated by ultrasonography were randomized into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1 ursodeoxycholic acid for three months. Abdominal computed tomography was performed to quantify hepatic fat content, which was significantly correlated with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass index remained stable for both groups throughout the study, but a significant reduction in mean (± SEM) serum levels of ALT, AST and gamma-GT was observed only in the treated group (ALT = 81.2 ± 9.7, 44.8 ± 7.7, 48.1 ± 7.7 and 52.2 ± 6.3 IU/l at the beginning and after the first, second and third months, respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 ± 9.8, 54.5 ± 7, 60 ± 7.6 and 43.7 ± 5 IU/l, respectively. No alterations in hepatic lipid content were observed in these patients by computed tomography examination (50.2 ± 4.2 Hounsfield units (HU) at the beginning versus 51.1 ± 4.1 HU at the third month). These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content.

Infrared coagulation versus rubber band ligation in early stage hemorrhoids

The ideal therapy for early stages of hemorrhoids is always debated. Some are more effective but are more painful, others are less painful but their efficacy is also lower. Thus, comfort or efficacy is a major concern. In the present randomized study, a comparison is made between infrared coagulation and rubber band ligation in terms of effectiveness and discomfort. One hundred patients with second degree bleeding piles were randomized prospectively to either rubber band ligation (N = 54) or infrared coagulation (N = 46). Parameters measured included postoperative discomfort and pain, time to return to work, relief in incidence of bleeding, and recurrence rate. The mean age was 38 years (range 19-68 years). The mean duration of disease was 17.5 months (range 12 to 34 months). The number of male patients was double that of females. Postoperative pain during the first week was more intense in the band ligation group (2-5 vs 0-3 on a visual analogue scale). Post-defecation pain was more intense with band ligation and so was rectal tenesmus (P = 0.0059). The patients in the infrared coagulation group resumed their duties earlier (2 vs 4 days, P = 0.03), but also had a higher recurrence or failure rate (P = 0.03). Thus, we conclude that band ligation, although more effective in controlling symptoms and obliterating hemorrhoids, is associated with more pain and discomfort to the patient. As infrared coagulation can be conveniently repeated in case of recurrence, it could be considered to be a suitable alternative office procedure for the treatment of early stage hemorrhoids.

Glutathione peroxidase induction protects Saccharomyces cerevisiae sod1deltasod2delta double mutants against oxidative damage

Saccharomyces cerevisiae mutants deficient in superoxide dismutase genes (sod1delta, sod2delta and the double mutant) were subjected to H2O2 stress in the stationary phase. The highest sensitivity was observed in the sod2delta mutant, while the sod1deltasod2delta double mutant was not sensitive. Sod mutants had lower catalase activity (44%) than wild-type cells, independent of H2O2 stress. Untreated cells of sod1deltasod2delta double mutants showed increased glutathione peroxidase activity (126%), while sod1delta had lower activity (77%) than the wild type. Glutathione levels in sod1delta were increased (200-260%) after exposure to various H2O2 concentrations. In addition, the highest malondialdehyde levels could be observed without H2O2 treatment in sod1delta (167%) and sod2delta (225%) mutants. In contrast, the level of malondialdehyde in the sod1deltasod2delta double mutant was indistinguishable from that of the wild type. These results suggest that resistance to H2O2 by sod1deltasod2delta cells depends on the induction of glutathione peroxidase and is independent of catalase, and that glutathione is a primary antioxidant in the defense against H2O2 in stationary phase sod1delta mutants.

Distortion and internal warping torsion of a double symmetric hollow section

This thesis is made in cooperation with Laboratory of Steel Structures and the steel company SSAB. Maximization of the benefits of high-strength steel usually requires the usage of thin wall thicknesses. This means the failures related to buckling, distortion and warping stand out. One must be aware of these phenomena to design thin-walled structures stressed with forces such as torsional loading. It is also important to take into account small stress ranges when evaluating the accurate fatigue strength of structures. The objective of this thesis is to clarify the theory of the uniform and non-uniform torsion. This paper focuses on warping due to the non-uniform torsion in double symmetric box girder and structural hollow section. The arisen stress states are explained and researched using the finite element method. Another research target is the distortion in double symmetric box girder due to torsion, and the restraining effect of transverse diaphragms at the load end. Multiple transverse diaphragms are used to study more efficient restraining against warping and distortion than a common one end plate structure.

A randomized, double-blind, and placebo-controlled study with tranexamic acid of bleeding and fibrinolytic activity after primary coronary artery bypass grafting

Cardiopulmonary bypass is frequently associated with excessive blood loss. Platelet dysfunction is the main cause of non-surgical bleeding after open-heart surgery. We randomized 65 patients in a double-blind fashion to receive tranexamic acid or placebo in order to determine whether antifibrinolytic therapy reduces chest tube drainage. The tranexamic acid group received an intravenous loading dose of 10 mg/kg, before the skin incision, followed by a continuous infusion of 1 mg kg-1 h-1 for 5 h. The placebo group received a bolus of normal saline solution and continuous infusion of normal saline for 5 h. Postoperative bleeding and fibrinolytic activity were assessed. Hematologic data, convulsive seizures, allogeneic transfusion, occurrence of myocardial infarction, mortality, allergic reactions, postoperative renal insufficiency, and reopening rate were also evaluated. The placebo group had a greater postoperative blood loss (median (25th to 75th percentile) 12 h after surgery (540 (350-750) vs 300 (250-455) mL, P = 0.001). The placebo group also had greater blood loss 24 h after surgery (800 (520-1050) vs 500 (415-725) mL, P = 0.008). There was a significant increase in plasma D-dimer levels after coronary artery bypass grafting only in patients of the placebo group, whereas no significant changes were observed in the group treated with tranexamic acid. The D-dimer levels were 1057 (1025-1100) µg/L in the placebo group and 520 (435-837) µg/L in the tranexamic acid group (P = 0.01). We conclude that tranexamic acid effectively reduces postoperative bleeding and fibrinolysis in patients undergoing first-time coronary artery bypass grafting compared to placebo.

A randomized double-blind clinical trial of the effect of non-absorbable oral polymyxin on infants with severe infectious diarrhea

The present study evaluated the effect of non-absorbable oral polymyxin on the duodenal microflora and clinical outcome of infants with severe infectious diarrhea. Polymyxin was chosen because classic enteropathogenic Escherichia coli was more sensitive to this antibiotic. Twenty-five infants were randomly assigned to a 7-day treatment with oral polymyxin (2.5 mg/kg in 4 daily doses) or placebo. Duodenal and stool cultures were performed before and after the treatment. Five patients were excluded during the study because of introduction of parental antibiotic therapy due to clinical sepsis (N = 3) or rapid clinical improvement (N = 2). In the polymyxin group, small bowel bacterial overgrowth occurred in 61.5% of the cases (8/13) before treatment and in 76.9% (10/13) after treatment. In the placebo group these values were 71.4% (5/7) and 57.1% (4/7), respectively. By the 7th day, clinical cure was observed in 84.6% of the cases (11/13) in the polymyxin group and in 71.4% (5/7) in the placebo group (P = 0.587). Considering all 25 patients included in the study, clinical cure occurred on the 7th day in 12/14 cases (85.7%) in the polymyxin group and 6/11 cases (54.5%) in the placebo group (P = 0.102). Clinical sepsis occurred in 3/11 (27.3%) of the patients in the placebo group and in none (0/14) in the polymyxin group (P = 0.071). Oral polymyxin was not effective in reducing bacterial overgrowth or in improving the clinical outcome of infants hospitalized with severe infectious diarrhea. Taking into account the small sample size, the rate of cure on the 7th day and the rate of clinical sepsis, further studies with greater number of patients are necessary to evaluate these questions.

Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy

Type II reaction in leprosy, or erythema nodosum leprosum (ENL), is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5% of the patients.

A double-blind comparison of the effect of the antipsychotics haloperidol and olanzapine on sleep in mania

The effects of haloperidol and olanzapine on polysomnographic measures made in bipolar patients during manic episodes were compared. Twelve DSM-IV mania patients were randomly assigned to receive either haloperidol (mean ± SD final dosage: 5.8 ± 3.8 mg) or olanzapine (mean ± SD final dosage: 13.6 ± 6.9 mg) in a 6-week, double-blind, randomized, controlled clinical trial. One-night polysomnographic evaluation was performed before and after the haloperidol or olanzapine treatment. Psychopathology and illness severity were rated respectively with the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions - Bipolar version (CGI-BP). There was a significant improvement in the YMRS and CGI-BP scores at the end of the study for both groups. Mixed ANOVA used to compare the polysomnographic measures of both drugs demonstrated significant improvement in sleep measures with olanzapine. In the olanzapine group, statistically significant time-drug interaction effects on sleep continuity measures were observed: sleep efficiency (mean ± SEM pre-treatment value: 6.7 ± 20.3%; after-treatment: 85.7 ± 10.9%), total wake time (pre-treatment: 140.0 ± 92.5 min; after-treatment: 55.2 ± 44.2 min), and wake time after sleep onset (pre-treatment: 109.7 ± 70.8 min; after-treatment: 32.2 ± 20.7 min). Conversely, improvement of polysomnographic measures was not observed for the haloperidol group (P > 0.05). These results suggest that olanzapine is more effective than haloperidol in terms of sleep-promoting effects, although olanzapine is comparatively as effective as haloperidol in treating mania. Polysomnography records should provide useful information on how manic states can be affected by psychopharmacological agents.

Modular Double-Cascade Converter

Medium-voltage motor drives extend the power rating of AC motor drives in industrial applications. Multilevel converters are gaining an ever-stronger foothold in this field. This doctoral dissertation introduces a new topology to the family of modular multilevel converters: the modular double-cascade converter. The modularity of the converter is enabled by the application of multiwinding mediumfrequency isolation transformers. Owing to the innovative transformer link, the converter presents many advantageous properties at a concept level: modularity, high input and output power quality, small footprint, and wide variety of applications, among others. Further, the research demonstrates that the transformer link also plays a key role in the disadvantages of the topology. An extensive simulation study on the new converter is performed. The focus of the simulation study is on the development of control algorithms and the feasibility of the topology. In particular, the circuit and control concepts used in the grid interface, the coupling configurations of the load inverter, and the transformer link operation are thoroughly investigated. Experimental results provide proof-of-concept results on the operation principle of the converter. This work concludes a research collaboration project on multilevel converters between LUT and Vacon Plc. The project was active from 2009 until 2014.