bluuebunny/crossref_metadata_2025_split huggingface dataset:
G20210A prothrombin gene mutation identified in patients with venous leg ulcers
Authors: Jebeleanu Gh. , Procopciuc Lucia 
Published: May 2007

AbstractThe G20210A mutation variant of prothrombin gene is the second most frequent mutation identified in patients withdeep venous thrombosis, after factor V Leiden. The risk for developing deep venous thrombosis is high in patients identified as heterozygous for G20210A mutation. In order to identify this polymorphism in the gene coding prothrombin, the 345bp fragment in the 3′‐ untranslated region of the prothrombin gene was amplified using amplification by polymerase chain reaction and enzymatic digestion by HindIII (restriction endonuclease enzyme). The products of amplification and enzymatic's digestion were analized using agarose gel electrophoresis. We investigated 20 patients with venous leg ulcers and we found 2 heterozygous (10%) for G20210A mutation. None of the patients in the control group had G20210A mutation. Our study confirms the presence of G20210A mutation in the Romanian population. Our study also shows the link between venous leg ulcers and this polymorphism in the prothrombin gene.
Basic studies on gene therapy of human malignant melanoma by use of the human interferon β gene entrapped in cationic multilamellar liposomes.: 1. Morphology and growth rate of six melanoma cell lines used in transfection experiments with the human interferon β gene
Authors: Benga Gh. 
Published: May 2007

AbstractSix cell lines of human malignant melanoma: A375, A375.2, G361, HMV‐1, MM8.1 and WM115 were seeded at densities of 1 × 104 cells/ml, 2 × 104 cells/ml or 3 × 104 cells/ml of RPMI medium supplemented with 10% fetal calf serum and antibiotics in a humidified atmosfere of 5% CO2 at 37°C. A375 cells were also grown in Dulbecco's minimum Eagle's medium (DMEM medium). The morphology was studied by phase contrast light microscopy. At 4 days after seeding the colonies of A375 cells and HMV‐1 cells were oval‐shaped, the cells were polyhedrical and were making contact with each other regularly. The remaining cells were scattered, more elongated, and made contact randomly. G361 cells and MM8.1 cells tended to form superposed layers before 100% confluency was achieved. There were great differences in the growth rate and doubling time of melanoma cells. The doubling time in day 1 was short (around 6‐12 h) in the case of A375, G361 and HMV‐1 cells, longer (around 18h) in the case of MM8.1 cells and very long (ranging between 26 and 89 h) for A375.2 and WM115 cells. There were also differences in the doubling time of cells as a function of the cell density at seeding. On the other hand, except for MM8.1 cells, there were differences between the doubling time in day 2 compared to day 1.
Influence of glutethimide on rat brain mononucleotides by sub‐chronic codeine treatment
Authors: Loghin Felicia , Popa Daniela‐Saveta , Socaciu Carmen 
Published: May 2007

AbstractIt was investigated the in vivo effect of glutethimide on the intracellular neuroadaptation characteristic for μ‐opioid receptor tolerance induced by chronic codeine treatment and reflected by increased levels of adenylyl cyclase (AC) and cAMP‐dependent protein kinase (PKA). AC activity was appreciated by cyclic‐AMP (cAMP) formation, the levels of adenine and guanine nucleotides in brain extracts being assayed using a high performance liquid chromatographic method. The concomitant chronic administration of codeine and glutethimide resulted in a pronounced and long‐lasting energetic depletion of the neurons, consistent with the high risk of overdose, and increase of cAMP's stable metabolite, 5′‐AMP. This increase is persistent even after withdrawal and suggests an interference with the adenylyl cyclase system involved in the development of tolerance of opioid receptor and in relapse and provides a possible explanation of addiction and fast increase of doses observed in humans abusing this combination.
Thalidomide as an anti‐cancer agent
Authors: Kumar S. , Witzig T. E. , Rajkumar S. V. 
Published: May 2007

AbstractThalidomide is a glutamic acid derivative initially introduced as a sedative hypnotic nearly forty years ago. It was withdrawn following numerous reports linking it to a characteristic pattern of congenital abnormalities in babies born to mothers who used the drug for morning sickness. It has gradually been re‐introduced into clinical practice over the past two decades, albeit under strict regulation, since it was found to be useful in the management of erythema nodosum leprosum and HIV wasting syndrome. Recognition of its anti‐angiogenic effect led to its evaluation in the treatment of various malignancies, where angiogenesis has been shown to play an important role. Numerous clinical trials done over the past four years have confirmed the significant anti‐myeloma activity of this drug. It has also shown promise in preliminary trials in the treatment of a variety of different malignant diseases. The mechanisms of its antineoplastic effects continue to be the focus of ongoing research. It has become clear that even though its anti angiogenic effects play a significant role in the anti‐tumor activity, there are other properties of this drug which are responsible as well. It also possesses anti‐TNF alpha activity, which has led to its evaluation in several inflammatory states. In this concise review, we briefly describe the historical background and pharmacological aspects of this drug. We have concisely reviewed the current knowledge regarding mechanisms of its anti‐neoplastic activity and the results of various clinical trials in oncology.
Determination of mitochondrial reactive oxygen species: methodological aspects
Authors: Batandier Cécile , Fontaine E. , Kériel Christiane , Leverve X. M. 
Published: May 2007

AbstractThe generation of Reactive Oxygen Species (ROS) as by‐products in mitochondria Electron Transport Chain (ETC) has long been admitted as the cost of aerobic energy metabolism with oxidative damages as consequence. The purpose of this methodological review is to present some of the most widespread methods of ROS generation and to underline the limitations as well as some problems, identified with some experiments as examples, in the interpretation of such results. There is now no doubt that besides their pejorative role, ROS are involved in a variety of cellular processes for the continuous adaptation of the cell to its environment. Because ROS metabolism is a complex area (low production, instability of species, efficient antioxidant defense system, several places of production…) bias, variances and limitations in ROS measurements must be recognized in order to avoid artefactual conclusions, and especially to improve our understanding of physiological and pathophysiological mechanisms of such phenomenon.
MYCL1, FHIT, SPARC, p16INK4 and TP53 genes associated to lung cancer in idiopathic pulmonary fibrosis
Authors: Demopoulos K. , Arvanitis D. A. , Vassilakis D. A. , Siafakas N. M. , Spandidos D. A. 
Published: May 2007

AbstractIdiopathic pulmonary fibrosis (IPF) is a specific form of chronic interstitial pneumonia limited to the lung and characterized by a fibroproliferative response with only minor signs of inflammation, which almost always causes rapid fibrotic destruction of the lung. In this study, we investigated genomic instability in IPF, using microsatellite DNA analysis, aiming to detect any specific genetic alterations for this disease. We used 40 highly polymorphic microsatellite DNA markers, in multiplex PCR assays, to examine 52 sputum specimens from IPF patients versus correspondent venous blood. Loss of heterozygosity (LOH) was found in 20 (38.5%) patients in at least one locus. These alterations were found on markers previously associated with lung cancer located on 1p34.3, 3p21.32‐p21.1, 5q32‐q33.1, 9p21 and 17p13.1 where MYCL1, FHIT, SPARC, p16Ink4 and TP53 genes have been mapped respectively. These data provide new insights into IPF pathogenesis and a new perspective for its correlation with lung cancer.
Few cultured rat primary sensory neurons express a tolbutamide‐sensitive K+ current
Authors: Ristoiu Violeta , Pluteanu Florentina , Flonta Maria‐Luiza , Reid G. 
Published: May 2007

AbstractThe response of dorsal root ganglion (DRG) neurons to metabolic inhibition is known to involve calcium‐activated K+ channels; in most neuronal types ATP‐sensitive K+ channels (KATP) also contribute, but this is not yet established in the DRG. We have investigated the presence of a KATP current using whole‐cell recordings from rat DRG neurons, classifying the neurons functionally by their “current signature” (Petruska et al, J Neurophysiol 84: 2365–2379, 2000). We clearly identified a KATP current in only 1 out of 62 neurons, probably a nociceptor. The current was activated by cyanide (2 mM NaCN) and was sensitive to 100 μM tolbutamide; the relation between reversal potential and external K+ concentration indicated it was a K+ current. In a further two neurons, cyanide activated a K+ current that was only partially blocked by tolbutamide, which may also be an atypical KATP current. We conclude that KATP channels are expressed in normal DRG, but in very few neurons and only in nociceptors.
Conversion of nucleotides sequences into genomic signals
Authors: Cristea P. D. 
Published: May 2007

AbstractAn original tetrahedral representation of the Genetic Code (GC) that better describes its structure, degeneration and evolution trends is defined. The possibility to reduce the dimension of the representation by projecting the GC tetrahedron on an adequately oriented plane is also analyzed, leading to some equivalent complex representations of the GC. On these bases, optimal symbolic‐to‐digital mappings of the linear, nucleic acid strands into real or complex genomic signals are derived at nucleotide, codon and amino acid levels. By converting the sequences of nucleotides and polypeptides into digital genomic signals, this approach offers the possibility to use a large variety of signal processing methods for their handling and analysis. It is also shown that some essential features of the nucleotide sequences can be better extracted using this representation. Specifically, the paper reports for the first time the existence of a global helicoidal wrapping of the complex representations of the bases along DNA sequences, a large scale trend of genomic signals. New tools for genomic signal analysis, including the use of phase, aggregated phase, unwrapped phase, sequence path, stem representation of components’relative frequencies, as well as analysis of the transitions are introduced at the nucleotide, codon and amino acid levels, and in a multiresolution approach.
Myocardial changes after spironolactone in spontaneous hypertensive rats. A laser scanning confocal microscopy study1
Authors: Pereira Leila Maria Meirelles , Mandarim‐de‐Lacerda C.A. 
Published: May 2007

AbstractThe present study aims to objectivate by laser scanning confocal microscopy, the cardiac structure of the spontaneously hypertensive rats (SHR) treated with different doses of spironolactone, either alone or in combination with an angiotensin converting enzyme inhibitor or with a calcium channel blocker. Thirty SHRs were divided into six groups and treated during 13 weeks as follows: control, spironolactone (5, 10 and 30 mg/kg/day), spironolactone + enalapril and spironolactone + verapamil. Spironolactone action on the SHR blood pressure (BP) was doses‐dependent. The cardiac hypertrophy was affected by the treatment with spironolactone (high dose) or a combination of spironolactone and Enalapril. The myocardial structure was less affected by the spironolactone monotherapy (at all doses) showing hypertrophied cardiac myocytes, focal areas of the reactive fibrosis, inflammatory infiltrate. The treatment with spironolactone in combination with enalapril or verapmil prevented these alterations. In conclusion, the monotherapy with spironolactone had only a limited effect in the preservation of the myocardial structure and in the attenuation of the interstitial fibrosis in SHRs, even after high dose. This action on the myocardium is more efficient when the spironolactone (even in medium dose) was associated with enalapril or verapamil.
Kinetics of apoptotic markers in exogeneously induced apoptosis of EL4 cells
Authors: Jessel Robert , Haertel Steffen , Socaciu Carmen , Tykhonova Svetlana , Diehl Horst A. 
Published: May 2007

AbstractWe investigated the time‐dependence of apoptotic events in EL4 cells by monitoring plasma membrane changes in correlation to DNA fragmentation and cell shrinkage. We applied three apoptosis inducers (staurosporine, tubericidine and X‐rays) and we looked at various markers to follow the early‐to‐late apoptotic events: phospholipid translocation (identified through annexin V‐fluorescein assay and propidium iodide), lipid package (via merocyanine assay), membrane fluidity and anisotropy (via fluorescent measurements), DNA fragmentation by the fluorescence‐labeling test and cell size measurements. The different apoptotic inducers caused different reactions of the cells: staurosporine induced apoptosis most rapidly in a high number of cells, tubercidine triggered apoptosis only in the S phase cells, while X‐rays caused a G2/M arrest and subsequently apoptosis. Loss of lipid asymmetry is promptly detectable after one hour of incubation time. The phosphatidylserine translocation, decrease of lipid package and anisotropy, and the increase of membrane fluidity appeared to be based on the same process of lipid asymmetry loss. Therefore, the DNA fragmentation and the cell shrinkage appear to be parallel and independent processes running on different time scales but which are kinetically inter‐related. The results indicate different signal steps to apoptosis dependent on inducer characteristics but the kinetics of “early‐to‐late” apoptosis appears to be a fixed program.
Molecular, immunological and clinical properties of mutated hepatitis B viruses
Authors: Kreutz C. 
Published: May 2007

AbstractHepatitis B virus (HBV) is at the origin of severe liver diseases like chronic active hepatitis, liver cirrhosis and hepatocellular carcinoma. There are some groups of patients with high risk of generation of HBV mutants: infected infants, immunosupressed individuals (including hemodialysis patients), patients treated with interferon and lamivudine for chronic HBV infection. These groups are the target for molecular investigations reviewed in this paper. The emergence of lamivudine‐ or other antiviral‐resistant variants, rises concern regarding long term use of these drugs. Infection or immunization with one HBV subtype confers immunity to all subtypes. However, reinfection or reactivation of latent HBV infection with HBV mutants have been reported in patients undergoing transplant and those infected with HIV. Mutations of the viral genome which are not replicative incompetent can be selected in further course of infection or under prolonged antiviral treatment and might maintain the liver disease. Four open reading frames (ORF) which are called S‐gene, C‐gene, X‐gene and P‐gene were identified within the HBV genome. Mutations may affect each of the ORFs. Mutated S‐genes were described to be responsible for HBV‐infections in successfully vaccinated persons, mutated C‐genes were found to provoke severe chronic liver diseases, mutated X‐genes could cause serious medical problemes in blood donors by escaping the conventional test systems and mutated P‐genes were considered to be the reason for chemotherapeutic drug resistance. This paper reviews molecular, immunological and clinical aspects of the HBV mutants.
Sarcolemmal and mitochondrial KATP channels and myocardial ischemic preconditioning
Authors: Peart J. N. , Gross G. J. 
Published: May 2007

AbstractIschemic preconditioning (IPC) is the phenomenon whereby brief periods of ischemia have been shown to protect the myocardium against a sustained ischemic insult. The result of IPC may be manifest as a marked reduction in infarct size, myocardial stunning, or incidence of arrhythmias. While many substances and pathways have been proposed to play a role in the signal transduction mediating the cardioprotective effect of IPC, overwhelming evidence indicates an intimate involvement of the ATP‐sensitive potassium channel (KATP channel) in this process. Initial hypotheses suggested that the surface or sarcolemmal KATP (sarcKATP) channel mediated the cardioprotective effects of IPC. However, much research has subsequently supported a major role for the mitochondrial KATP channel (mitoKATP) as the one involved in IPC‐mediated cardioprotection. This review presents evidence to support a role for the sarcKATP or the mitoKATP channel as either triggers and/or downstream mediators in the phenomenon of IPC.
Designing of ‘intelligent’ liposomes for efficient delivery of drugs
Authors: Voinea Manuela , Simionescu Maya 
Published: May 2007

AbstractThe liposome‐ vesicles made by a double phospholipidic layers which may encapsulate aqueous solutions‐ have been introduced as drug delivery vehicles due to their structural flexibility in size, composition and bilayer fluidity as well as their ability to incorporate a large variety of both hydrophilic and hydrophobic compounds. With time the liposome formulations have been perfected so as to serve certain purposes and this lead to the design of “intelligent” liposomes which can stand specifically induced modifications of the bilayers or can be surfaced with different ligands that guide them to the specific target sites. We present here a brief overview of the current strategies in the design of liposomes as drug delivery carriers and the medical applications of liposomes in humans.
Neural stem cells in aging and disease
Authors: Limke T. L. , Rao Mahendra S. 
Published: May 2007

AbstractAging in the central nervous system is associated with progressive loss of function which is exacerbated by neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The two primary cell replacement strategies involve transplantation of exogenous tissue, and activation of proliferation of endogenous cells. Transplanted tissue is used to either directly replace lost tissue, or to implant genetically engineered cells that secrete factors which promote survival and/or proliferation. However, successful application of any cell replacement therapy requires knowledge of the complex relationships between neural stem cells and the more restricted neural and glial progenitor cells. This review focuses on recent advances in the field of stem cell biology of the central nervous system, with an emphasis on cellular and molecular approaches to replacing cells lost in neurodegenerative disorders.
Reactive oxygen species, antioxidant mechanisms and serum cytokine levels in cancer patients: impact of an antioxidant treatment
Authors: Mantovani G. , Macciò A. , Madeddu C. , Mura L. , Massa E. , Gramignano G. , Lusso M. R. , Murgia V. , Camboni P. , Ferreli L. 
Published: May 2007

Abstract Objective. So far, it is not well established whether oxidative stress found in cancer patients results from an increased production of oxidants in the body or from a failure of physiological antioxidant systems. To further investigate this question we have assessed the blood levels of reactive oxygen species as a marker of free radicals producing oxidative stress and the most relevant of the physiological body enzymes counteracting reactive oxygen species, namely glutathione peroxidase and superoxide dismutase. Serum levels of proinflammatory cytokines and IL‐2 were also investigated. All these parameters were studied in relation to the clinically most important index of disease progression, namely Performance Status (ECOG PS). We also tested the reducing ability of different antioxidant agents on reactive oxygen species levels by measuring the increase in glutathione peroxidase activity, and the reduction of serum levels of IL‐6 and TNF. Design, setting and subjects. We carried out an open non randomized study on 28 advanced stage cancer patients (stage III, 10.7%, and stage IV, 89.3%) with tumours at different (8) sites: all were hospitalized in the Medical Oncology Dept, University of Cagliari Interventions. The patients were divided into 5 groups and a different antioxidant treatment was administered to each group. The selected antioxidants were: alpha lipoic acid 200 mg/day orally, N‐acetylcysteine 1800 mg/day i.v. or carboxycysteine‐lysine salt 2.7 g/day orally, amifostine 375 mg/day i.v., reduced glutathione 600 mg/day i.v., vitamin A 30000 IU/day orally plus vitamin E 70 mg/day orally plus Vitamin C 500 mg/day orally. The antioxidant treatment was administered for 10 consecutive days. Results. Our results show that all but one of the antioxidants tested were effective in reducing reactive oxygen species levels and 2 of them (cysteine‐containing compounds and amifostine) had the additional effect of increasing glutathione peroxidase activity. Comprehensively, the “antioxidant treatment” was found to have an effect both on reactive oxygen species levels and glutathione peroxidase activity. The antioxidant treatment also reduced serum levels of IL‐6 and TNF. Patients in both ECOG PS 0‐1 and ECOG PS 2‐3 responded to antioxidant treatment.
Blood histamine is associated with coronary artery disease, cardiac events and severity of inflammation and atherosclerosis
Authors: Clejan Sanda , Japa Shenkar , Clemetson C. , Hasabnis Sanjeev S. , David Odile , Talano J. V. 
Published: May 2007

Abstract Background: Mast cells are prevalent in the shoulder of unstable atheromas; cardiac mast cells secrete proteases capable of activating matrix metalloproteinases. Histamine is essential in the inflammatory cascade of the unstable plaque. Ascorbate depletion has been correlated with histaminemia which has been shown to impair endothelial‐dependent vasodilation. This study evaluates whether oxidative stress as measured by isoprostanes (PGF2α) coupled with an inflammatory state characterized by histaminemia predisposes patients to acute coronary syndrome (ACS). Methods: Whole blood histamine, serum vitamin C, and serum PGF2α levels were drawn on 50 patients with ACS as determined by standard diagnostic criteria, 50 patients with stable coronary artery disease (SCAD), and 50 age and sex matched normal controls (C). Results: Data were analyzed by stepwise discriminant and Spearman's rank correlation coefficient. A significant relationship exists between histamine and PGF2α. As PGF2α rises above 60 pg/mL, an increase in histamine occurs in both the ACS and SCAD groups. A significant inverse relationship exists between ascorbate and histamine in the ACS versus C groups (P < 0.01) and the SCAD versus C groups (P < 0.01). Conclusion: Histamine and isoprostane levels increase in SCAD and ACS patients. Mast cell activation and lipid oxidation generated during atherosclerosis manifest this inflammatory response. Accelerated isoprostane formation and depleted ascorbate paired with histaminemia is active in CAD and predispose patients to acute coronary syndrome. Blood histamine alone may be a better risk factor for coronary events, and a better prognostic indicator than CRP even when combined with lipid indexes.
Stem cells (p63+) in keratinocyte cultures from human adult skin
Authors: Radu E. , Siminoescu Olga , Regalia T. , Dumitrescu Doina , Popescu L. M. 
Published: May 2007

AbstractEpidermal stem cells (ESC) are responsible for maintaining skin cellular homeostasis, as they give rise to fast‐dividing transit amplifying cells committed to terminal differentiation, while retaining their self‐renewal capacity. However, no pure ESC cultures are available and no highly specific cytochemical marker was identified. We report here the experimental conditions allowing the selective enrichment in ESC, using cultured adult human keratinocytes. The main step was the selection of cells able to rapidly adhere to human collagen type IV in vitro. Thus, an increased proportion of putative ESC of about 65% was obtained, as demonstrated by p63 expression.