Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 ± 0.9 days; 2369 ± 491 g) were randomly assigned to receive saline (placebo, P) or the AT1 receptor (AT1-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO2 = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT1-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT1-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT1-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT1-R staining, but C animals showed weak iNOS and AT1-R staining. Macrophages of L and P animals showed moderate and weak AT2-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT1-R blockade. We suggest that AT1-R blockade might act through AT2-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA+ was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the χ² test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.

Relationship of macrophage migration inhibitory factor levels in PBMCs, lesional skin and serum with disease severity and activity in vitiligo vulgaris

Melanocyte loss in vitiligo vulgaris is believed to be an autoimmune process. Macrophage migration inhibitory factor (MIF) is involved in many autoimmune skin diseases. We determined the possible role of MIF in the pathogenesis of vitiligo vulgaris, and describe the relationship between MIF expressions and disease severity and activity. Serum MIF concentrations and mRNA levels in PBMCs were measured in 44 vitiligo vulgaris patients and 32 normal controls, using ELISA and real-time RT-PCR. Skin biopsies from 15 patients and 6 controls were analyzed by real-time RT-PCR. Values are reported as median (25th-75th percentile). Serum MIF concentrations were significantly increased in patients [35.81 (10.98-43.66) ng/mL] compared to controls [7.69 (6.01-9.03) ng/mL]. MIF mRNA levels were significantly higher in PBMCs from patients [7.17 (3.59-8.87)] than controls [1.67 (1.23-2.42)]. There was also a significant difference in MIF mRNA levels in PBMCs between progressive and stable patients [7.86 (5.85-9.13)vs 4.33 (2.23-8.39)] and in serum MIF concentrations [40.47 (27.71-46.79) vs 26.80 (10.55-36.07) ng/mL]. In addition, the vitiligo area severity index scores of patients correlated positively with changes of both serum MIF concentrations (r = 0.488) and MIF mRNA levels in PBMCs (r = 0.426). MIF mRNA levels were significantly higher in lesional than in normal skin [2.43 (2.13-7.59)vs 1.18 (0.94-1.83)] and in patients in the progressive stage than in the stable stage [7.52 (2.43-8.84)vs 2.13 (1.98-2.64)]. These correlations suggest that MIF participates in the pathogenesis of vitiligo vulgaris and may be useful as an index of disease severity and activity.

Relationship between genetic mutation variations and acute-phase reactants in the attack-free period of children diagnosed with familial Mediterranean fever

Familial Mediterranean fever (FMF) is a periodic autoinflammatory disease characterized by chronic inflammation. This study investigated the relationship between acute-phase reactants and gene mutations in attack-free periods of childhood FMF. Patients diagnosed with FMF were divided into four groups based on genetic features: no mutation, homozygous, heterozygous, and compound heterozygous. These groups were monitored for 2 years, and blood samples were collected every 6 months during attack-free periods. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and white blood cell count were measured. A disease severity score was determined for each patient. Mean values for erythrocyte sedimentation rate and fibrinogen were significantly different in the homozygous group. White blood cell count and C-reactive protein were similar between the groups. Disease severity score was higher in patients with the M694V mutation than in individuals without the mutation, as well as in those with other mutation groups. Periodic follow-up of patients with FMF MEFV mutations in subjects with acute-phase reactants may be useful in the prevention of morbidity.

Relationship of inflammatory markers and pain in patients with head and neck cancer prior to anticancer therapy

Pain is a common symptom in patients with cancer, including those with head and neck cancer (HNC). While studies suggest an association between chronic inflammation and pain, levels of inflammatory cytokines, such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), have not been correlated with pain in HNC patients who are not currently undergoing anticancer treatment. The purpose of this study was to examine the relationship between these inflammatory markers and perceived pain in HNC patients prior to anticancer therapy. The study group consisted of 127 HNC patients and 9 healthy controls. Pain was assessed using the Brief Pain Inventory (BPI), and serum levels of CRP and TNF-α were determined using the particle-enhanced turbidimetric immunoassay (PETIA) and ELISA techniques, respectively. Patients experiencing pain had significantly higher levels of CRP (P<0.01) and TNF-α (P<0.05) compared with controls and with patients reporting no pain. There were significantly positive associations between pain, CRP level, and tumor stage. This is the first study to report a positive association between perceived pain and CRP in HNC patients at the time of diagnosis. The current findings suggest important associations between pain and inflammatory processes in HNC patients, with potential implications for future treatment strategies.

Relationship between pulmonary function and indoor air pollution from coal combustion among adult residents in an inner-city area of southwest China

Few studies evaluate the amount of particulate matter less than 2.5 mm in diameter (PM2.5) in relation to a change in lung function among adults in a population. The aim of this study was to assess the association of coal as a domestic energy source to pulmonary function in an adult population in inner-city areas of Zunyi city in China where coal use is common. In a cross-sectional study of 104 households, pulmonary function measurements were assessed and compared in 110 coal users and 121 non-coal users (≥18 years old) who were all nonsmokers. Several sociodemographic factors were assessed by questionnaire, and ventilatory function measurements including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and peak expiratory flow rate (PEFR) were compared between the 2 groups. The amount of PM2.5 was also measured in all residences. There was a significant increase in the relative concentration of PM2.5 in the indoor kitchens and living rooms of the coal-exposed group compared to the non-coal-exposed group. In multivariate analysis, current exposure to coal smoke was associated with a 31.7% decrease in FVC, a 42.0% decrease in FEV1, a 7.46% decrease in the FEV1/FVC ratio, and a 23.1% decrease in PEFR in adult residents. The slope of lung function decrease for Chinese adults is approximately a 2-L decrease in FVC, a 3-L decrease in FEV1, and an 8 L/s decrease in PEFR per count per minute of PM2.5 exposure. These results demonstrate the harmful effects of indoor air pollution from coal smoke on the lung function of adult residents and emphasize the need for public health efforts to decrease exposure to coal smoke.

Relationship between deep venous thrombosis and inflammatory cytokines in postoperative patients with malignant abdominal tumors

Deep venous thrombosis (DVT) is a common surgical complication in cancer patients and evidence that inflammation plays a role in the occurrence of DVT is increasing. We studied a population of cancer patients with abdominal malignancies with the aim of investigating whether the levels of circulating inflammatory cytokines were associated with postoperative DVT, and to determine the levels in DVT diagnoses. The serum levels of C-reactive protein (CRP), interleukins (IL)-6 and IL-10, nuclear transcription factor-κB (NF-κB) and E-selectin (E-Sel) were determined in 120 individuals, who were divided into 3 groups: healthy controls, patients with and patients without DVT after surgery for an abdominal malignancy. Data were analyzed by ANOVA, Dunnet's T3 test, chi-square test, and univariate and multivariate logistic regression as needed. The CRP, IL-6, NF-κB, and E-Sel levels in patients with DVT were significantly higher than those in the other groups (P<0.05). The IL-10 level was higher in patients with DVT than in controls but lower than in patients without DVT. Univariate analysis revealed that CRP, IL-6, NF-κB, and E-Sel were statistically associated with the risk of DVT (OR=1.98, P=0.002; OR=1.17, P=0.000; OR=1.03, P=0.042; and OR=1.38, P=0.003; respectively), whereas IL-10 had a protective effect (OR=0.94, P=0.011). Multivariate analysis showed that E-Sel was an independent risk factor (OR=1.41, P=0.000). Thus, this study indicated that an increased serum level of E-Sel was associated with increased DVT risk in postoperative patients with abdominal malignancy, indicating that E-Sel may be a useful predictor of diagnosis of DVT.

Relationship between salt consumption measured by 24-h urine collection and blood pressure in the adult population of Vitória (Brazil)

High salt intake is related to an increase in blood pressure and development of hypertension. However, currently, there are no national representative data in Brazil using the gold standard method of 24-h urine collection to measure sodium consumption. This study aimed to determine salt intake based on 24-h urine collection in a sample of 272 adults of both genders and to correlate it with blood pressure levels. We used a rigorous protocol to assure an empty bladder prior to initiating urine collection. We excluded subjects with a urine volume <500 mL, collection period outside of an interval of 23-25 h, and subjects with creatinine excretion that was not within the range of 14.4-33.6 mg/kg (men) and 10.8-25.2 mg/kg (women). The mean salt intake was 10.4±4.1 g/day (d), and 94% of the participants (98% of men and 90% of women) ingested more than the recommended level of 5 g/d. We found a positive association between salt and body mass index (BMI) categories, as well as with salt and blood pressure, independent of age and BMI. The difference in systolic blood pressure reached 13 mmHg between subjects consuming less than 6 g/d of salt and those ingesting more than 18 g/d. Subjects with hypertension had a higher estimated salt intake than normotensive subjects (11.4±5.0 vs 9.8±3.6 g/d, P<0.01), regardless of whether they were under treatment. Our data indicate the need for interventions to reduce sodium intake, as well the need for ongoing, appropriate monitoring of salt consumption in the general population.

Expression of merlin, NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence

Meningiomas are common, usually benign tumors of the central nervous system that have a high rate of post-surgical recurrence or regrowth. We determined expression of the proteins merlin, NDRG2, ERBB2, and c-MYC in meningiomas using immunohistochemistry and assessed relationships between protein expression and gender, age, tumor grade, and recurrence or regrowth. The study sample comprised 60 patients, (44 women and 16 men) with a mean age of 53.2±12.7 years. Tumors were classified as grade I (n=48) or grades II and III (n=12). Expression of merlin, NDRG2, ERBB2, and c-MYC was not significantly different statistically with relation to gender, age, or meningioma recurrence or regrowth. Merlin was expressed in 100% of the cases. No statistically significant difference between tumor grade and recurrence or regrowth was identified. Statistically significant differences were identified between the mean age of patients with grade I (54.83±11.60) and grades II and III (46.58±15.08) meningiomas (P=0.043), between strong c-MYC expression and grades II and III (P<0.001), and between partial surgical resection and tumor recurrence or regrowth (P<0.001). These findings reveal the lower mean age among grades II and III meningioma patients than grade I patients, the influence of the protein merlin on tumorigenesis, the association of c-MYC with aggressive meningiomas, and that partial surgical resection is associated with tumor recurrence or regrowth.

IT-toimittajan valinta pk-yrityksissä

Työssä tutkitaan pk-yritysten IT-toimittajan valintaan liittyviä tekijöitä. Tutkimuksella on kolme tavoitetta, jotka ovat tutkia tekijöitä, jotka liittyvät pk-yrityksen IT-toimittajan valintaan, mitkä tekijät ovat tärkeimmät IT-toimittajan valinnassa ja kuinka valinta IT-toimittajasta tehdään. Työ on tapaustutkimus, joka koostuu teoreettisesta kirjallisuusselvityksestä ja empiirisestä tapaustutkimuksesta. Empiirisen aineiston hankintaan on käytetty kvalitatiivista menetelmää. Tutkimustavoitteiden saavuttamiseksi suoritettiin kymmenen teemahaastattelua tutkimukseen mukaan valittujen kymmenen pk-yritysten kanssa. Haastattelut analysoitiin käyttäen sisällönanalyysiä, jossa käytettiin kirjallisuusselvityksen pohjalta valittuja kuutta eri näkökulmaa. Näkökulmiksi valittiin ostokäyttäytyminen, liiketoimintahyödyt, organisaation vaikutus, IT-toimittajasta koettu arvo, yrityksen IT-valmiudet ja IT-toimittajan ominaisuudet. Tutkimuksen perusteella IT-toimittajan valintaan liittyviä tekijöitä ovat yrityksen toimiala, ikä ja koko; organisaation resurssit, rakenne ja IT-osaaminen; IT-toimittajan tarjooma, ominaisuudet ja myyntitaidot; henkilökohtaiset suhteet, kuulopuheet ja sattumat. Tärkeimmiksi tekijöiksi IT-toimittajan valinnassa nousivat toimittajan nopeus reagoida asiakkaan tarpeisiin ja toimittajan luotettavuus. IT-toimittajat valitaan pk-yrityksissä vaihtelevasti joko kilpailuttamalla, tuttavuussuhteen, kuulopuheen tai tuntuman perusteella. IT-toimittajan valinnan tärkeys tulee korostumaan tulevaisuudessa pk-yrityksissä, jotka tulevat kukin toimialakohtaisesti kohtaamaan digitalisaation tuomat haasteet ja mahdollisuudet. Pk-yritysten tulisi keskittyä löytämään IT-toimittaja, joka auttaa heitä tulevaisuudessa kehittämään IT:tä yhä enemmän tukemaan heidän liiketoimintaa ja luomaan uusia mahdollisuuksia.

The Impact of the 2007-2009 Financial Crisis on the Relationship between Central Bank Rates and the Corresponding Interbank Interest Rates in 2002-2014

The role of central banks throughout the global financial system has become even more important during and after the events of the financial crisis. In order to stabilize the market conditions and provide solid ground for future development, the central banks use discount rate as their primary monetary policy tool in many developed and emerging economies. The purpose of this thesis is to examine how the relationship between central bank rates and corresponding interbank rates has developed before, during and after the crisis period of 2007-2009 in five developed countries and five emerging market countries. The results indicate that during the before-crisis period the interest rate markets reacted diversely but the joint recovery attempts of global economies seem to have stabilized the reactions during and especially after the crisis. The crisis also seems to have highlighted the characteristics of each country’s survival strategy as the role of other policy instruments arose.