Effects of chronic ethanol treatment on monoamine levels in rat hippocampus and striatum

We studied the effects of ethanol on concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5-HT) and their metabolites in rat hippocampus and striatum. Ethanol (2 or 4 g/kg, po, from a 20% aqueous solution) was administered daily to male Wistar rats (4-13 per group) for 30 days and animals were sacrificed 30 min or 48 h after the last administration. Monoamines were measured by HPLC and considered significant at P < 0.05. A 47% increase in 5-HT levels was observed in the hippocampus with 4 g/kg ethanol in the 30-min protocol. Ethanol (2 and 4 g/kg) decreased DA (2114.5 ± 126.4 and 1785.1 ± 234.2 ng/g wet tissue, respectively) and 3,4-dihydroxyphenylacetic acid (DOPAC, 1477.6 ± 132.1 and 1218.8 ± 271.7 ng/g wet tissue, respectively) levels, while the higher dose also decreased NE (159.8 ± 13.5), 5-HT (228.0 ± 46.8) and 5-hydroxy-3-indoleacetic acid (5-HIAA, 304.4 ± 37.2 ng/g wet tissue), in the striatum after a 48-h withdrawal as compared to controls (DA: 3063.9 ± 321.3; DOPAC: 2379.6 ± 256.0; NE: 292.8 ± 50.2; 5-HT: 412.4 ± 36.2; 5-HIAA: 703.9 ± 61.4 ng/g wet tissue). In the 30-min protocol, ethanol (2 or 4 g/kg) decreased striatal NE (66 and 70%) and DA (50 and 36%) levels. On the other hand, increases were seen in 5-HIAA (146 and 153%) and 5-HT (59 and 86%) levels. Ethanol (2 g/kg, po) increased the homovanillic acid (HVA)/DA ratio (129%) in the striatum in the 30-min protocol, while at the higher dose it increased the HVA/DA ratio in the 48-h protocol (61%). These results indicate alterations in monoamines, mainly in the striatum, after chronic ethanol, which are influenced by dose and by the length of time after the last drug administration.

Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event

Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. The objective of this study was to examine the major determinants of coronary disease severity, including those coronary risk factors associated with metabolic syndrome, during the early period after an acute coronary episode. We tested the hypothesis that inflammatory markers, especially highly sensitive C-reactive protein (hsCRP), are related to coronary atherosclerosis, in addition to traditional coronary risk factors. Subjects of both genders aged 30 to 75 years (N = 116) were prospectively included if they had suffered a recent acute coronary syndrome (acute myocardial infarction or unstable angina pectoris requiring hospitalization) and if they had metabolic syndrome diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III. Patients were submitted to a coronary angiography and the burden of atherosclerosis was estimated by the Gensini score. The severity of coronary disease was correlated (Spearman’s or Pearson’s coefficient) with gender (r = 0.291, P = 0.008), age (r = 0.218, P = 0.048), hsCRP (r = 0.256, P = 0.020), ApoB/ApoA ratio (r = 0.233, P = 0.041), and carotid intima-media thickness (r = 0.236, P = 0.041). After multiple linear regression, only male gender (P = 0.046) and hsCRP (P = 0.012) remained independently associated with the Gensini score. In this high-risk population, male gender and high levels of hsCRP, two variables that can be easily obtained, were associated with more extensive coronary disease, identifying patients with the highest potential of developing new coronary events.

Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

Photodynamic therapy (PDT) mediated by oxidative stress causes direct tumor cell damage as well as microvascular injury. To improve this treatment new photosensitizers are being synthesized and tested. We evaluated the effects of PDT with 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin (TMPP) and its zinc complex (ZnTMPP) on tumor levels of malondialdehyde (MDA), reduced glutathione (GSH) and cytokines, and on the activity of caspase-3 and metalloproteases (MMP-2 and -9) and attempted to correlate them with the histological alterations of tumors in 3-month-old male Wistar rats, 180 ± 20 g, bearing Walker 256 carcinosarcoma. Rats were randomly divided into five groups: group 1, ZnTMPP+irradiation (IR) 10 mg/kg body weight; group 2, TMPP+IR 10 mg/kg body weight; group 3, 5-aminolevulinic acid (5-ALA+IR) 250 mg/kg body weight; group 4, control, no treatment; group 5, only IR. The tumors were irradiated for 15 min with red light (100 J/cm², 10 kHz, 685 nm) 24 h after drug administration. Tumor tissue levels of MDA (1.1 ± 0.7 in ZnTMPP vs 0.1 ± 0.04 nmol/mg protein in control) and TNF-α (43.5 ± 31.2 in ZnTMPP vs 17.3 ± 1.2 pg/mg protein in control) were significantly higher in treated tumors than in controls. Higher caspase-3 activity (1.9 ± 0.9 in TMPP vs 1.1 ± 0.6 OD/mg protein in control) as well as the activation of MMP-2 (P < 0.05) were also observed in tumors. These parameters were correlated (Spearman correlation, P < 0.05) with the histological alterations. These results suggest that PDT activates the innate immune system and that the effects of PDT with TMPP and ZnTMPP are mediated by reactive oxygen species, which induce cell membrane damage and apoptosis.

MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

The matrix metalloprotease-1 (MMP-1)/protease-activated receptor-1 (PAR-1) signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC), we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9%) and 58 (68.2%) tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM) stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS) than those with negative ESCC (P = 0.002 and 0.003, respectively). Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR) = 2.836, 95% confidence interval (CI) = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068), MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127), and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883) and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681), MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279), and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881) as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

Participation of the NO/cGMP/K+ATP pathway in the antinociception induced by Walker tumor bearing in rats

Implantation of Walker 256 tumor decreases acute systemic inflammation in rats. Inflammatory hyperalgesia is one of the most important events of acute inflammation. The L-arginine/NO/cGMP/K+ATP pathway has been proposed as the mechanism of peripheral antinociception mediated by several drugs and physical exercise. The objective of this study was to investigate a possible involvement of the NO/cGMP/K+ATP pathway in antinociception induced in Walker 256 tumor-bearing male Wistar rats (180-220 g). The groups consisted of 5-6 animals. Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. Walker tumor (4th and 7th day post-implantation) reduced prostaglandin E2- (PGE2, 400 ng/paw; 50 µL; intraplantar injection) and carrageenan-induced hypernociception (500 µg/paw; 100 µL; intraplantar injection). Walker tumor-induced analgesia was reversed (99.3% for carrageenan and 77.2% for PGE2) by a selective inhibitor of nitric oxide synthase (L-NAME; 90 mg/kg, ip) and L-arginine (200 mg/kg, ip), which prevented (80% for carrageenan and 65% for PGE2) the effect of L-NAME. Treatment with the soluble guanylyl cyclase inhibitor ODQ (100% for carrageenan and 95% for PGE2; 8 µg/paw) and the ATP-sensitive K+ channel (KATP) blocker glibenclamide (87.5% for carrageenan and 100% for PGE2; 160 µg/paw) reversed the antinociceptive effect of tumor bearing in a statistically significant manner (P < 0.05). The present study confirmed an intrinsic peripheral antinociceptive effect of Walker tumor bearing in rats. This antinociceptive effect seemed to be mediated by activation of the NO/cGMP pathway followed by the opening of KATP channels.

Philosophia moralis sive ethica (1662)

Nimiösivulla myös motto: Augustinus ad Maced: Virtus eo pluris aestimanda est, quo plura contemnit.

The consensus sequence of FAMLF alternative splice variants is overexpressed in undifferentiated hematopoietic cells

The familial acute myeloid leukemia related factor gene (FAMLF) was previously identified from a familial AML subtractive cDNA library and shown to undergo alternative splicing. This study used real-time quantitative PCR to investigate the expression of the FAMLF alternative-splicing transcript consensus sequence (FAMLF-CS) in peripheral blood mononuclear cells (PBMCs) from 119 patients with de novo acute leukemia (AL) and 104 healthy controls, as well as in CD34+cells from 12 AL patients and 10 healthy donors. A 429-bp fragment from a novel splicing variant of FAMLF was obtained, and a 363-bp consensus sequence was targeted to quantify total FAMLF expression. Kruskal-Wallis, Nemenyi, Spearman's correlation, and Mann-Whitney U-tests were used to analyze the data. FAMLF-CS expression in PBMCs from AL patients and CD34+ cells from AL patients and controls was significantly higher than in control PBMCs (P<0.0001). Moreover,FAMLF-CS expression in PBMCs from the AML group was positively correlated with red blood cell count (rs=0.317, P=0.006), hemoglobin levels (rs=0.210, P=0.049), and percentage of peripheral blood blasts (rs=0.256, P=0.027), but inversely correlated with hemoglobin levels in the control group (rs=–0.391, P<0.0001). AML patients with high CD34+ expression showed significantly higherFAMLF-CS expression than those with low CD34+ expression (P=0.041). Our results showed thatFAMLF is highly expressed in both normal and malignant immature hematopoietic cells, but that expression is lower in normal mature PBMCs.

Vakka-Suomen seudun liikenneturvallisuussuunnitelma

Vakka-Suomen seudun liikenneturvallisuussuunnitelma on laadittu seudun kuntien, Varsinais-Suomen ELY-keskuksen, Liikenneturvan ja Lounais-Suomen poliisilaitoksen yhteistyönä. Liikenneturvallisuussuunnitelman tavoitteena on edistää nykyistä vastuullisempaa ja turvallisuushakuisempaa liikkumiskulttuuria. Suunnittelun lähtökohtana on ollut EU-tason liikenneturvallisuusvisio, jonka mukaan ”liikennejärjestelmä on suunniteltava siten, ettei kenenkään tarvitse kuolla eikä loukkaantua vakavasti liikenteessä”. Visio tukeutuu näkemykseen, että puutteellinen liikenneturvallisuus on laaja kansanterveydellinen ongelma, joka koskettaa monia yhteiskunnan sektoreita. Liikenneturvallisuusongelmien ratkaisemiseksi tarvitaan useita keinoja ja monen osapuolen yhteistyötä. Liikenneturvallisuussuunnitelmassa asetetaan tiukat tavoitteet liikenneonnettomuuksien määrän vähentämiseksi vuoteen 2025 mennessä. Liikennekuolemien osalta tavoitteena on lisätä niin sanottujen ”nollavuosien” määrää. Tavoitteena on myös vähentää loukkaantumisten, etenkin vakavien loukkaantumisten, määrää merkittävästi. Tavoitteiden saavuttamiseksi on laadittu monipuolinen päättäjien hyväksymille painopistealueille kohdennettu toimenpideohjelma. Suunnitelmaan sisältyy toimenpide-ehdotuksia liittyen yhteistyöhön, liikennekasvatukseen ja -tiedotukseen, liikenneympäristön parantamiseen, liikenteen valvontaan sekä liikenteen ja maankäytön suunnitteluperiaatteisiin. Suunnitelman toteuttamisen vastuu jakautuu toimenpiteen luonteesta riippuen kuntasektorille, ELY-keskukselle, Liikenneturvalle, poliisille ja muille sidosryhmille. Liikenneonnettomuuksien määrän vähentäminen säästää inhimilliseltä kärsimykseltä ja yhteiskunnalle kaivattuja kustannussäästöjä. Liikenneonnettomuuksista aiheutuu vuosittain seudun kunnille noin neljän miljoonan euron laskennalliset kustannukset. Liikenneturvallisuuden parantuminen asetettujen tavoitteiden mukaisesti tarkoittaisi karkeastikin arvioiden miljoonaluokan säästöjä kuntasektorille. Vähintään yhtä tärkeänä tavoitteena on koetun liikenneturvallisuuden parantuminen, joka vaikuttaa keskeisesti ihmisten hyvinvointiin. Suunnitelman vaikutustenarvioinnin perusteella voidaan todeta, että keinot asetettujen tavoitteiden saavuttamiseksi ovat olemassa, mutta tavoitteisiin pääseminen edellyttää erittäin suuria panostuksia kaikilla liikenneturvallisuustyön osa-alueilla, ja erityisesti liikennekäyttäytymiseen ja yhteistyöhön kohdistuvien toimenpiteiden osalta. Pelkästään sillä, että kaikki käyttäisivät laissa määrättyjä turvalaitteita ja liikenteestä saataisiin pois rattijuopot, itsemurhat, sairaskohtaukset ja ylinopeudet, säästettäisiin vuosittain seudulla jopa neljä henkeä. Liikenneympäristöön kohdennetut toimet ovat nekin tärkeitä, mutta niillä voidaan saavuttaa vain pieni osa asetetuista tavoitteista. Koetun turvallisuuden osalta turvallisen liikenneympäristön vaikutus on sitäkin merkittävämpi.

Evaluation of the use of PetrifilmTM EB count plates for the enumeration of Enterobacteriaceae in poultry samples

A test that is rapid, simple, accurate, not expensive, gives rapid results, and is sensitive enough to detect low levels of microorganisms would be the most suitable for food industry routine laboratories, or even for a public health laboratories. A ready-to-use alternative, commercially available method is the PetrifilmTM EB method. The aim of this study was to evaluate whether there is a statistically significant difference between the conventional methods based on Violet Red Bile Glucose Agar and the alternative 3M TM Petrifilm (EB) method for the enumeration of Enterobacteriaceae in poultry carcasses. This study also assessed whether the alternative method showed ability to produce results that were directly proportional to the concentration of the target (approximately 270 colony-forming unit.mL-1). A total of 120 poultry carcasses samples showed a significant difference (p < 0.05) between the populations obtained by the two methods, and the conventional method showed low proportionality between the dilutions. On the other hand, the PetrifilmTM EB quantification system showed the capacity to produce results that are proportional to the concentration of the analyte in samples in the concentration range from 1 to 256 colony-forming unit.mL-1.

Keittiön kautta politiikkaan : konsulttivalta

Kirjallisuusarvostelu

Yliopistot keskiajan sosiaalisena innovaationa : paavi, ruhtinas ja kaupunki

Teema: Yliopistohistoria.