bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein folding
Authors: Basharov M. A. 
Published: May 2007

AbstractThe problem of protein folding is that how proteins acquire their native unique three‐dimensional structure in the physiological milieu. To solve the problem, the following key questions should be answered: do proteins fold co‐ or post‐translationally, i.e. during or after biosynthesis, what is the mechanism of protein folding, and what is the explanation for fast folding of proteins? The two first questions are discussed in the current review. The general lines are to show that the opinion, that proteins fold after they are synthesized is hardly substantiated and suitable for solving the problem of protein folding and why proteins should fold cotranslationally. A possible tentative model for the mechanism of protein folding is also suggested. To this end, a thorough analysis is made of the biosynthesis, delivery to the folding compartments, and the rates of the biosynthesis, translocation and folding of proteins. A cursory attention is assigned to the role of GroEL/ES‐like chaperonins in protein folding.
Regulation of apoptosis by Bcl‐2 family proteins
Authors: Burlacu Alexandrina 
Published: May 2007

AbstractFor multicellular organisms, the rigorous control of programmed cell death is as important as that of cell proliferation. The mechanisms involved in the regulation of cell death are not yet understood, but a key component is the family of caspases which are activated in a cascade and are responsible for the apoptotic‐specific changes and disassembly of the cell. Although the caspases represent a central point in apoptosis, their activation is regulated by a variety of other factors. Among these, Bcl‐2 family plays a pivotal role in caspases activation, by this deciding whether a cell will live or die. Bcl‐2 family members are known to focus much of their response to the mitochondria level, upstream the irreversible cellular damage, but their functions are not yet well defined. This review summarizes the recent data regarding the Bcl‐2 proteins and the ways they regulate the apoptosis.
Catalytic antibodies in healthy humans and patients with autoimmune and viral diseases
Authors: Nevinsky G. A. , Buneva Valentina N. 
Published: May 2007

AbstractAntibodies have been first characterized as proteins produced by the immune system solely for binding other molecules, called antigens, with the goal of eliciting immune response. In this classical conception, antibodies act similarly to enzymes in specific binding to different molecules but cannot catalyze their chemical conversion. However, in 1986 the first monoclonal catalytic antibodies against a chemically stable analog of the transition state of a reaction were obtained and termed abzymes (Abzs). At present, artificial monoclonal Abzs catalyzing more than 100 distinct chemical reactions have been obtained. The discovery of IgG specifically hydrolyzing intestinal vasoactive peptide in the blood serum of asthma patients stimulated studies of natural Abzs. Numerous Abzs discovered afterwards in sera of patients with various autoimmune diseases, viral disorders, or in the milk of healthy mothers, are capable of hydrolyzing proteins, DNA, RNA, polysaccharides, or nucleotides, as well as to phosphorylate proteins and lipids. The phenomenon of catalysis by auto‐Abzs is more and more in research focus. In this review we summarize new data on Abzs applications in basic science, medicine and biotechnology.
Attenuation of changes in Gi‐proteins and adenylyl cyclase in heart failure by an ACE inhibitor, imidapril
Authors: Sethi R. , Shao Q. , Takeda N. , Dhalla N. S. 
Published: May 2007

AbstractCardiac dysfunction in animals with congestive heart failure due to myocardial infarction (MI) is known to be associated with a wide variety of defects in receptor and post‐receptor mechanisms. Since the heart function have been shown to be improved by treatment with different angiotensin converting enzyme (ACE) inhibitors, we examined the effects of imidapril, an ACE inhibitor, on changes in post‐receptor mechanisms involving adenylyl cyclase (AC) and G proteins in the failing heart. Heart failure in rats was induced by occluding the coronary artery and 3 weeks later the animals were treated daily with 1 mg/kg (orally) imidapril for 5 weeks. The animals were assessed for their left ventricular function and crude membranes were isolated from the viable left ventricle and examined for AC activities as well as G‐protein activities and expression. Animals with heart failure exhibited depressions in ventricular function and AC activities in the absence or presence of forskolin, NaF and Gpp(NH)p. The AC activity in the presence of pertussis toxin was increased whereas that in the presence of cholera toxin was decreased in the failing heart. Protein contents and mRNA levels for Gi‐proteins were increased whereas those for Gs‐proteins were unaltered in the infarcted heart. All these changes due to MI were prevented by imidapril treatment. The results indicate that the depressed cardiac function in the failing heart may partly be due to the direct effects of changes in AC and Gi proteins.
Correlation between the predicted and the observed biological activity of the symmetric and nonsymmetric cyclic urea derivatives used as HIV‐1 protease inhibitors. A 3D‐QSAR‐CoMFA method for new antiviral drug design
Authors: Avram Speranta , Svab I. , Bologa C. , Flonta Maria‐Luiza 
Published: May 2007

AbstractThe predicted inhibition constant (Ki) and the predicted inhibitor concentration (IC90) of the HIV‐1 protease (HIV‐1 PR) inhibitors: symmetric and nonsymmetric ‐ benzyl, ketone, oxime, pyrazole, imidazole, and triazole cyclic urea derivatives, were obtained by the 3D‐CoMFA (Comparative Molecular Field Analysis) method. The CoMFA statistical parameters: cross‐validate correlation coefficient (q2), higher than 0.5, and the fitted correlation coefficient (r2), higher than 0.90 validated the predicted biological activities. The best predictions were found for the trifluoromethyl ketoxime derivative (log 1/Ki predict = 8.42), the m‐pyridineCH2 pyrazole derivative (log 1/Ki predict = 9.77) and the 1,2,3 triazole derivative (log 1/Ki predict = 7.03). We attempted to design a new potent HIV‐1 protease inhibitor by addition of o‐benzyl to the (p‐HOPhCH2) pyrazole 12f derivative inhibitor. A favorable steric area surrounded the o‐benzyl, suggesting a possible new potent HIV‐1 protease inhibitor.
Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats
Authors: Shinde Urmila A. , Goyal R. K. 
Published: May 2007

AbstractEarlier studies from our laboratory have indicated insulin sensitizing action of chromium picolinate as the mechanism of its anti‐diabetic activity in experimental models of type I and type II diabetes. In the present investigation, we have evaluated the effects of chronic administration of chromium picolinate on the functional and histological alterations of streptozotocin (STZ)‐induced diabetes in rats. Type I diabetes was induced by intravenous injection of STZ (40 mg/kg) in adult rats, whereas, type II diabetes was induced by intraperitoneal injection of STZ (90 mg/kg) in 2‐day old rat pups which in adulthood develop abnormalities resembling type II diabetes. Chromium picolinate was administered at 8 μg/ml in drinking water for 6 weeks and was found to improve glucose tolerance and increase insulin sensitivity of STZ‐diabetic rats. This treatment decrease elevated serum creatinine and urea levels as well as elevated serum levels of hepatic enzymes of both groups of diabetic rats. Histopathological studies of kidney and liver show decrease in the intensity and incidence of vacuolations, cellular infiltration and hypertrophy of STZ and nSTZ (neonatal STZ) diabetic rats. Chronic treatment with chromium picolinate however, did not alter the normal function or morphology of control rats. Chronic chromium picolinate at the therapeutic doses that improved glucose tolerance, was observed to have no hepatotoxic or nephrotoxic potential. It was rather found to improve renal and hepatic function and to reduce abnormalities associated with STZ‐diabetes. Chromium picolinate could play an important role in the long term management of diabetes mellitus.
Ischemia induces short‐ and long‐term remodeling of synaptic activity in the hippocampus
Authors: Crepel Valérie , Epsztein J. , Ben‐Ari Y. 
Published: May 2007

AbstractOne of the most vulnerable areas to ischemia or hypoglycemia is CA1 hippocampal region due to pyramidal neurons death. Glutamate receptors are involved together with protein‐kinase C and nitric oxide synthase. Long‐term potentiation (LTP) is generated in anoxic or hypoglycemic conditions via activation of NMDA while inhibition of these receptors atenuates this response. Protein‐kinase C and nitric oxide synthase are involved in anoxic LTP mechanism. Postischemic neurons are hyperexcitable in CA3 area while CA1 pyramidal neurons degenerate and dissapear. Changes of glutamate receptors triggered by ischemia and hypoglycemia are discussed in this review.
Endotoxin translocation in two models of experimental acute pancreatitis
Authors: Vasilescu C. , Herlea V. , Buttenschoen K. , Beger H. G. 
Published: May 2007

AbstractTo test the hypothesis that endotoxin is absorbed from the gut into the circulation in rats with experimental acute pancreatitis we studied two different animal models. In the first model necrotizing pancreatitis was induced by the ligation of the disatl bilio‐pancreatic duct while in the second, experimental oedematous acute pancreatitis was induced by subcutaneous injections of caerulein. In both experiments, in the colon of rats with acute pancreatitis endotoxin from Salmonella abortus equi was injected. Endotoxin was detected by immunohistochemistry in peripheral organs with specific antibodies. The endotoxin was found only in rats with both acute pancreatitis and endotoxin injected into the colon and not in the control groups. The distribution of endotoxin in liver at 3 and 5 days was predominantly at hepatocytes level around terminal hepatic venules, while in lung a scattered diffuse pattern at the level of alveolar macrophages was identified. A positive staining was observed after 12 hours in the liver, lung, colon and mesenteric lymph nodes of rats with both caerulein pancreatitis and endotoxin injected into the colon. We conclude that the experimental acute pancreatitis leads to early endotoxin translocation from the gut lumen in the intestinal wall and consequent access of gut‐derived endotoxin to the mesenteric lymph nodes, liver and lung.
Phenotypic characterization of mouse embryonic fibroblasts lacking heat shock factor 2
Authors: Paslaru Liliana , Morange M. , Mezger Valérie 
Published: May 2007

AbstractIn murine cells, the heat shock response is regulated by a transcription factor, HSF1, which triggers the transcription of heat shock genes. HSF2 has been shown to be involved in meiosis and mouse brain development. We characterized the effects of the absence of HSF2 in mouse embryonic fibroblasts (MEFs). The temperature threshold of the heat shock response appeared lowered in Hsf2‐/‐ MEFS as monitored by the synthesis of heat shock protein HSP70. In contrast to unstressed wild type MEFS, HSP70 and HSF1 are localized in the nucleus of unstressed Hsf2‐/‐ MEFS, a characteristic of stressed cells. HSF1 is not activated for DNA‐binding at unstressed temperature in Hsf2‐/‐ MEFS. Therefore, the absence of HSF2 induces some but not all of the characteristics of the stress response. In addition, Hsf2‐/‐ MEFS exhibited proliferation defects, altered morphology, remodeling of the fibronectin network.
The influence of sodium metavanadate on the process of diabetogenesis in BB rats
Authors: Cheta D. , Orasanu Gabriela , Nicolaie T. , Iordachescu Dana , Buligescu S. , Constantin C. , Hassanain M. , Coman Anca , Enache Mihaela , Negru Raluca , Tica Valeria , Timofte Delia , Gutu Daniela , Panaite C. 
Published: May 2007

AbstractVanadium has been shown to be beneficial in the oral treatment of animal models of type 1 and type 2 diabetes. The aim of the study was to evaluate the short‐term effects of sodium metavanadate in prediabetic BB‐DP rats. To do this, 96 rats were divided into 4 equal groups. Groups VI, V2, V3 were treated with sodium metavanadate (0.1, 0.2 and 0.3 mg/ml respectively) and sodium chloride (0.5 mg/ml) in drinking water for 7 days. Group C received only sodium chloride (0.5 mg/ml). Blood glucose (BG), glycosuria, ketonuria, body weight and insulinemia were determined. The age of onset of diabetes was significantly higher for groups V2, V3 compared to group C, (p < 0.05) and depends on the metavanadate concentration (V3 vs. V1, p=0.006). The incidence of diabetes was lower in the rats treated with metavanadate than in the control group, but this difference was not statistically significant. In diabetic rats, the BG at the onset was higher in group C than in groups V, p < 0.05. Insulinemia, at the onset of the treatment as well as immediately after its cessation showed a drop in the treatment groups, proportionally to the dosage of vanadium, but later increased slowly and continuously until the end of the experiment. In conclusion, metavanadate delays the development of diabetes in BB‐DP rats, but does not prevent its onset. A milder form of diabetes occurs in diabetic rats treated with metavanadate. The effects depend on the metavanadate concentration and 0.2 mg/ml is preferable.
Endothelial cells from hematopoietic stem cells are functionally different from those of human umbilical vein
Authors: Paunescu V. , Suciu Erika , Tatu C. , Plesa Adriana , Herman Diana , Siska Ioana Raluca , Suciu C. , Crisnic Daniela , Nistor Daciana , Tanasie Gabriela , Bunu Carmen , Raica M. 
Published: May 2007

AbstractHematopoietic stem cells have a remarkable plastic capacity, which allows them to differentiate into various cells, such as immune cells, nervous cells, muscle cells, bone and cartilaginous cells. The aim of this study was to show the capacity of stem cells to differentiate into endothelial cells, in culture, after addition of endothelial cells growth suplement (ECGS). We also compared the behavior of these cells with that of endothelial cells obtained from human umbilical vein (HUVEC). CD34+ cells obtained by immunomagnetic separation from human umbilical cord and placental blood were used. After 12‐15 days of culture in a medium containing ECGS, the cells showed morphological changes characteristic to endothelial cells and immunocytochemical analysis revealed the presence of CD31 surface antigen and von Willebrand factor. The flow‐cytometric analysis of endothelial cells adhesion molecules (ECAM) showed that endothelial cells derived from CD34+ cells expressed CD54/ICAM‐1 9.65 ± 0.2% and CD106/VCAM 7.73±0.3%, values similar to those expressed by HUVECs. After TNF incubation, ECAM expression increased only in HUVECs. These data demonstrate that a fraction of circulating CD34+ cells may develop some endothelial cell characteristics when cultured with ECGS, but they are functionally different from HUVECs.
Interleukin‐17 in acute myeloid leukemia
Authors: Wróbel T. , Mazur G. , Jazwiec Bozena , Kuliczkowski K. 
Published: May 2007

AbstractThere are several reports that angiogenesis plays important roles in hematological malignancies including acute myeloid leukemia (AML). Human interleukin‐17 (IL‐17) is a proinflammatory cytokine produced by activated CD4 T cells. IL‐17 plays a potential role in T cell mediated angiogenesis. The role of IL‐17 in pathologic angiogenesis has not been evaluated yet. The aim of the study was to determine plasma level of IL‐17 in patients with AML. IL‐17 levels were measured by ELISA in plasma samples taken from 68 adult patients with AML before chemotherapy was administered. In addition 20 out of 68 patients were reanalysed after achieving complete remission (CR). Ten samples from healthy volunteers were evaluated as the control. In this study we have demonstrated that serum level of IL‐17 is not elevated in AML patients. These results suggest that angiogenesis in AML is not mediated by CD4 T cells. To our knowledge this is the first report about IL‐17 serum level in acute leukemias. We are currently evaluating IL‐17 levels in others haematological malignancies.
New asthma drugs acting on gene expression
Authors: Popescu F.‐D. 
Published: May 2007

AbstractNew asthma drugs acting on transcription are transcription factor agonists (dissociated steroids, peroxisome proliferator‐activated receptor gamma agonists), transcription factor inhibitors (NF‐kB / AP‐1 inhibitors, STAT6 inhibitors), inhibitors of protein kinases acting on transcription factors (p38 MAP kinase inhibitors), and chromatin modifying agents. Pharmacological approach of translation in asthma includes therapeutic ribozymes and antisense oligonucleotides targeting receptors (adenosine A1 receptor, alpha chain of IL‐5 receptor, common beta chain of IL‐3/IL‐5/GM‐CSF receptor), cytokines (IL‐4, IL‐5, SCF), signal transduction molecules (Syk, Lyn), transcription factors (STAT‐6, GATA‐3). Some of these drugs acting on gene expression have the potential to improve therapeutic benefits compared with traditional drugs.
Molecular pathology in the diagnosis and treatment of non‐Hodgkin's lymphomas
Authors: Krause J. R. , Shahidi‐Asl Mahnaz 
Published: May 2007

AbstractThe non‐Hodgkin's lymphomas encompass a wide spectrum of hematologic neoplasms that exhibit different clinical and biological features. Lymphomas classically have been initially assessed based on their cytologic and histologic features. Morphology alone is often inadequate as similar appearing neoplasms may be immunophenotypically and molecularly heterogeneous. Molecular diagnostic methods can provide an additional level of testing that not only helps refine diagnoses but can provide prognostic information. New methods are being refined that may provide information to establish precise diagnostic profiles, provide targets for therapy and provide more sensitive methods for monitoring the success of treatment. Molecular methods will be increasingly utilized and eventually required as the accepted method of diagnosis and for monitoring the disease. Understanding of the molecular abnormality and the pathogenesis of the neoplasm hopefully will lead to therapeutic intervention aimed at the specific molecular defect or its product. The molecular pathology of the non‐Hodgkin's lymphomas is discussed.
Renal cortex remodeling in nitric oxide deficient rats treated with enalapril
Authors: Barbuto Noemi , Almeida Jorge Reis , Pereira Leila Maria Meirelles , Mandarim‐de‐Lacerda Carlos Alberto 
Published: May 2007

AbstractThe kidney NO synthase is one of the most important renal controlling systems. This paper aims the quantification of renal cortical components involved in blood pressure regulation under NOs blockade. Spontaneous hypertensive rats (SHRs) are submitted to chronic blockade of NOs by L‐nitro‐arginine‐methyl‐ester (L‐NAME) and an ACE inhibitor (enalapril) in comparison with the normotensive Wistar rats. Twenty SHRs and 5 Wistar rats were divided in 5 groups and observed for 21 days for blood pressure (BP) and serum creatinine: control Wistar (5) (C‐W), control SHR (5) (C‐SHR), L‐SHR (5) ‐ received L‐NAME 30 mg/kg/day, L+E‐SHR (5) ‐ received L‐NAME and Enalapril maleate 15 mg/kg/day, E‐SHR (5) ‐ received Enalapril maleate. A quantitative morphometric study (glomerular density, QA[g1], interstitium volume density, Vv[i], tubular surface and length densities, Sv[t] and Lv[t]) were performed at the end. The BP reached 226±15 mmHg in L‐SHR group. The BP difference between the L‐SHR and the C‐SHR groups was significant from the first week while the E‐SHR group became significant from the second week. At the end of the experiment the BP of the E‐SHR group was similar to the BP in the C‐W group. The QA[g1] was similar among C‐SHR, L‐SHR and L+E‐SHR groups and no difference was found between E‐SHR and C‐W groups. In the L‐SHRs serum creatinine was greatly increased, and microscopy showed thickening of arteriolar tunica media with an increase of the wall‐to‐lumen ratio, perivascular fibrosis, inflammatory infiltrated, tubular atrophy and interstitial fibrosis with focal segmental glomerulosclerosis. The use of enalapril was not completely efficient in reducing BP and morphological injury when the hypertension of SHRs was increased with the NOs blockade suggesting that NO deficiency‐induced hypertension is not entirely mediated by the RAAS.
Topical superoxide dismutase reduces post‐irradiation breast cancer fibrosis
Authors: Campana F. , Zervoudis S. , Perdereau B. , Gez E. , Fourquet A. , Badiu C. , Tsakiris G. , Koulaloglou S. 
Published: May 2007

AbstractFibrosis following breast radiotherapy for mammary cancer is a frequent undesired effect with objective (esthetic) and subjective (pain) consequences. Forty‐four patients with clinical radiofibrosis following conservative treatment of breast cancer were evaluated for the local antifibrosis effect of copper zinc superoxide dismutase [SOD(Cu/Zn)]. Extracted SOD(Cu/Zn) in a concentration of 3,600 units/mg was applied as ointment to the fibrotic affected area, b.i.d. for 90 days, in a total dose of 40 mg. The radiofibrosis intensity was scored on the basis of clinical criteria (pain and the fibrosis area) before and after SOD(Cu/Zn) treatment. SOD(Cu/Zn) was found to be effective in reducing radiation induced fibrosis by a lowering pain score in 36/39 patients and a decrease of the fibrotic area size in half cases, after 6 months. The intensity and changes of breast fibrosis were assessed also by mammography and, for the topographical distribution of subcutaneous temperature, by infrared thermography. Mammography density suggested decreased fibrosis in one third of patients. Thermography showed that fibrosis was accompanied by two zones clinically indistinctive: a central area with maximum thermal activity, called “Maximal Thermic zone” (MTZ) and a peripheral area with less thermal activity but higher than in the surrounding normal tissue, “Transitional Thermic Zone” (TTZ). Both MTZ and TTZ were significantly decreased in 36/44 patients after SOD(Cu/Zn) treatment. Clinical changes persisted all along the study. Treatment was well tolerated except for one case of local allergic reaction, and no important side effects. Molecular mechanisms involved are discussed. Further studies are running to confirm and explain these results.
β‐secretase‐cleaved amyloid precursor protein in Alzheimer brain: a morphologic study
Authors: Sennvik Kristina , Bogdanovic N. , Volkmann Inga , Fastbom J. , Benedikz E. 
Published: May 2007

Abstractβ‐amyloid (Aβ) is the main constituent of senile plaques seen in Alzheimer's disease. Aβ is derived from the amyloid precursor protein (APP) via proteolytic cleavage by proteases β‐ and β‐secretase. In this study, we examined content and localization of β‐secretase‐cleaved APP (β‐sAPP) in brain tissue sections from the frontal, temporal and occipital lobe. Strong granular β‐sAPP staining was found throughout the gray matter of all three areas, while white matter staining was considerably weaker. β‐sAPP was found to be localized in astrocytes and in axons. We found the β‐sAPP immunostaining to be stronger and more extensive in gray matter in Alzheimer disease (AD) cases than controls. The axonal β‐sAPP staining was patchy and unevenly distributed for the AD cases, indicating impaired axonal transport. β‐sAPP was also found surrounding senile plaques and cerebral blood vessels. The results presented here show altered β‐sAPP staining in the AD brain, suggestive of abnormal processing and transport of APP.