The nucleotide sequence of a Polish isolate of Tomato torrado virus

A new virus was isolated from greenhouse tomato plants showing symptoms of leaf and apex necrosis in Wielkopolska province in Poland in 2003. The observed symptoms and the virus morphology resembled viruses previously reported in Spain called Tomato torrado virus (ToTV) and that in Mexico called Tomato marchitez virus (ToMarV). The complete genome of a Polish isolate Wal’03 was determined using RT-PCR amplification using oligonucleotide primers developed against the ToTV sequences deposited in Genbank, followed by cloning, sequencing, and comparison with the sequence of the type isolate. Phylogenetic analyses, performed on the basis of fragments of polyproteins sequences, established the relationship of Polish isolate Wal’03 with Spanish ToTV and Mexican ToMarV, as well as with other viruses from Sequivirus, Sadwavirus, and Cheravirus genera, reported to be the most similar to the new tomato viruses. Wal’03 genome strands has the same organization and very high homology with the ToTV type isolate, showing only some nucleotide and deduced amino acid changes, in contrast to ToMarV, which was significantly different. The phylogenetic tree clustered aforementioned viruses to the same group, indicating that they have a common origin. The nucleotide sequence of the Wal’03 isolate reported in this article has been submitted to the GenBank and is available under accession numbers: EU563948 (RNA1) and EU563947 (RNA2).     

Derivatives of pyrrolo[3,4-d]pyridazinone, a new class of analgesic agents

A series of N2-{2-[4-aryl(benzyl)-1-piperazinyl(piperidinyl)]ethyl}pyrrolo[3,4-d]pyridazinones 4 and related derivatives 5 were synthesized as potential analgesic agents. The structures of the new compounds were elucidated by micro, spectral and X-ray analysis. Analgesic activity of the compounds was investigated in the phenylbenzoquinone induced ‘writhing’ and ‘hot plate’ test in mice and at radioligand binding assay. At ‘writhing’ test all compounds, without exception, were more active than acetylsalicylic acid (ASA) with ED₅₀ values ranging from 0.04 to 11 mg/kg (i.p.) (ED₅₀ for ASA - 39.15 mg/kg). Analgesic effect at the ‘hot plate’ test was observed for three compounds 4c,e,f at the dose 3-5 times higher then that of morphine (ED₅₀-3.39 mg/kg). At radioligand binding assay of 4c,e,f only compound 4f exhibited affinity for the μ-opioid receptors similar to that of Tramadol. The acute toxicity of the pyrrolopyridazinones 4, 5 were also studied and non toxic effect was observed at the 2000 mg/kg (5a 1420 mg/kg) i.p. dose level. On the basis of the available pharmacological data S-A relationship is discussed. The preferred conformational characteristic of 4, taken 4c as an example, was also described.     

Concentration of nitric oxide in exhaled air in patients with sarcoidosis--pilot study

Exhaled nitric oxide (eNO) concentration measurement may allow for noninvasive estimation of severity of airways inflammation in asthma and other airways diseases. The purpose of this study was to evaluate usefulness of eNO concentration measurements in patients with pulmonary sarcoidosis. Study group consisted of 22 patients with sarcoidosis (8 women, 14 men aged 26-46). They included 11 patients with radiographically stage I and II and 11 patients with stage III of disease. Sixteen patients had active pulmonary sarcoidosis and 6 had nonactive disease. Ten patients had indications for treatment, 12 patients had not any. Exhaled NO was measured by means of SIEVERS 280 Nitric Oxide Analyser (USA). There was no significant difference in mean eNO concentration in study group (6.91 +/- 0.60 ppb) and in normal control (5.2 +/- 0.73 ppb, p = 0.10). Exhaled NO concentration was similar in patients with sarcoidosis stage I and II (7.5 +/- 1.08 ppb) and in patients with stage III disease (6.2 +/- 0.51 ppb, p = 0.27). We failed to found significant difference in eNO concentration between patients with active (6.7 +/- 0.71 ppb) and nonactive sarcoidosis (7.5 +/- 1.1 ppb; p = 0.57). Neither did eNO concentration differ between patients with and without indications for therapy (5.77 +/- 0.50 ppb vs. 7.8 +/- 0.95 ppb; p = 0.08). In conclusion our pilot study results indicate that measurement of eNO concentrations may be of little value in patients with sarcoidosis.     

A preliminary study of apoptosis induction in glioma cells via alteration of the Bax/Bcl-2-p53 axis by transformed and non-transformed root extracts of Leonurus sibiricus L.

Tumor Biology - Leonurus sibiricus L. is a traditional medicinal plant which occurs in southern Siberia, China, Korea, Japan, and Vietnam. The plant shows several pharmacological effects, but the...     

Noninvasively assessed pulsatility of ascending aortic pressure waveform is associated with the presence of coronary artery narrowing

Several hemodynamic indices, measured invasively in the ascending aorta during routine angiography, are related to the presence and severity of coronary atherosclerosis. Radial artery tonometry, when combined with a validated transfer function, offers the possibility of noninvasive assessment of central arterial pressure. We aim to evaluate the association between noninvasive indices of aortic or radial pressure waveforms and the presence of a significant coronary stenosis. Patients who underwent elective coronary angiography were studied (110 men, 91 women, mean age 53 ± 0.9 years). Noninvasive measurement of their central hemodynamics was performed by analysis of the aortic pressure waveform derived from the radial artery. An increase in aortic fractional pulse pressure was associated with coronary artery narrowing or previous myocardial infarction. After multivariate adjustment, the odds ratio and confidence intervals (CI) of having a significant coronary aortic stenosis was 1.72 (95% CI, 1.1–2.7) and of previous myocardial infarction 1.6 (95% CI, 1.1–2.2). An increase in noninvasively assessed aortic fractional pulse pressure, but not of the peripheral index is significantly associated with the presence of coronary artery disease.     

Cortical dopaminergic neurotransmission in rats intoxicated with lead during pregnancy. Nitric oxide and hydroxyl radicals formation involvement

It is well established that low level Pb-exposure is associated with a wide range of cognitive and neurobehavioral dysfunctions in children. In fact, Pb-induced damage occurs preferentially in the prefrontal cerebral cortex, hippocampus and cerebellum - the anatomical sites which are crucial in modulating emotional response, memory and learning. Previously it was also shown that nitric oxide (NO) signaling pathway as well as glutamatergic neurotransmission are both involved in brain development, neurotoxicity and neurodegeneration processes whereas Pb(2+) interfere with both. For this reason we investigated the effect of ontogenetic Pb(2+) exposure on dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) of rats after amphetamine (AMPH) and/or 7-nitroindazole (7-NI) administration. Furthermore, the possible role of oxidative stress in Pb(2+)-induced neurotoxicity in prenatally Pb(2+)-treated rats was explored in the content of hydroxyl radical (HO(*)) species in mPFC after AMPH and/or 7-NI injection, assessed by HPLC analysis of 2.3-dihydroxybenzoic acid (2.3-DHBA) - spin trap product of salicylate. As shown, the results of this study suggest that Pb(2+) exposure during intrauterine life did not substantially affect cortical dopaminergic neurotransmission in adult offspring rats evaluated by means of microdialysis of mPFC and the content of the cortical HO(*). It is likely that striatum, nucleus accumbens or other dopamine rich brain areas are more intricately associated with Pb(2+) precipitated behavioral, dopamine - dependent impairments observed in mammalians.     

Diagnostic power of VEGF,MMP-9 and TIMP-1 in patients with breast cancer. A multivariate statistical analysis with ROC curve

PurposeVascular endothelial growth factor is an important factor in promoting angiogenesis in malignant processes, matrix metalloproteinase-9 in the degradation of extracellular matrix, which enhances metastasis, and tissue inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to investigate the diagnostic power of these parameters in comparison to CA15-3 in breast cancer patients and in relation to the control group.Materials/methodsThe study included 120 breast cancer patients, 60 patients with benign breast tumors and 60 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle immuno assay.ResultsTissue inhibitor of metalloproteinase-1 showed the highest value of sensitivity in breast cancer group (86.25%) and, more importantly, highest value in breast cancer stage I (85%). Vascular endothelial growth factor also showed high sensitivity (stage I and II–75%, III–85%, IV–70% and 76.25% in total breast cancer group) and the highest specificity (85%) from all tested parameters. It was also the only parameter which had statistically significant area under curve in all stages. In the total breast cancer group all tested parameters showed statistically significant area under curve, but the maximum range was obtained for combination: ‘vascular endothelial growth factor + CA15-3′. Vascular endothelial growth factor seems to be the best candidate for diagnosing breast cancer stage I and for differentiating between breast cancer and non-carcinoma cases.ConclusionsThe combined analysis of tested parameters and CA15-3 resulted in an increase in sensitivity and area under curve values, which provides hope for developing new panel of biomarkers that may be used in diagnosing breast cancer in the future.