Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitric oxide as a mediator of cocaine‐induced penile erection in the rat

1 . The effect of local application of cocaine to the corpus cavemosum on intracavemous pressure (ICP), an experimental index for penile erection, was examined in Sprague‐Dawley rats anaesthetized with chloral hydrate. The potential involvement of dopamine, noradrenaline or nitric oxide as the chemical mediator in this process, and the pharmacological action of cocaine as a local anaesthetic in the induced increase in ICP, were also investigated. 2 . Intracavemous (i.e.) administration of cocaine (40, 80 or 160 μg) to the corpus cavemosum resulted in a dose‐related increase in both amplitude and duration of ICP. 3 . The elevation in ICP induced by cocaine (160 μg, i.e.) was not significantly influenced by prior injection into the corpus cavemosum of either the D1 or D2 dopamine receptor antagonist, R‐(+)‐SCH 23390 (250 pmol) or (—)‐sulpiride (250 pmol). 4 . Similarly, penile erection promoted by cocaine (160 μg, i.e.) was not appreciably affected by i.e. pretreatment with the α1, α2‐, or β‐adrenoceptor antagonist, prazosin (50 pmol), yohimbine (50 pmol) or propranolol (5 nmol). 5 . Whereas lignocaine (4 μmol, i.e.) depressed penile erection induced by papaverine (400 μg, i.e.), local application of cocaine (160 μg) into the corpus cavemosum still elicited significant elevation in ICP in the presence of lignocaine or papaverine. 6 . The increase in ICP induced by cocaine (160 μg, i.e.) was attenuated dose‐dependently by prior cavemosal administration of the NO synthase inhibitor, Nω‐nitro‐L‐arginine methyl ester (1‐NAME, 0.5, 1 or 5 pmol) or NG‐monomethyl‐L‐arginine (L‐NMMA, 2.5, 5 or 10 pmol). The blunting effect of L‐NAME or L‐NMMA was reversed by co‐administration of the NO precursor, L‐arginine (1 nmol, i.e.). 7 . Pretreatment by local application into the corpus cavemosum of methylene blue (2.5 μmol), an inhibitor of cytosolic guanylyl cyclase, antagonized cocaine‐induced penile erection. 8 . Direct i.e. administration of a NO donor, nitroglycerin (10 or 20 nmol), mimicked the local action of cocaine by promoting a significant increase in ICP. 9 . It is concluded that cocaine may induce penile erection by increasing ICP via a local action on the corpus cavemosum. This process did not appear to involve either dopamine or noradrenaline as the chemical mediator, nor the pharmacological action of cocaine as a local anaesthetic. On the other hand, it is likely that initiation and maintenance of penile erection elicited by cavemosal application of cocaine engaged an active participation of NO and subsequent activation of guanylyl cyclase in the corpus cavemosum.
Serum creatinine level and renal function in children.

OBJECTIVE To evaluate the accuracy of serum creatinine and height/serum creatinine glomerular filtration rate (Cr-GFR) formula as screening tests for abnormal renal function defined by plasma diethylenetriaminepenta-acetic acid (DTPA) clearance. DESIGN Patient series. SETTING The Children's Hospital of Buffalo (NY). PATIENTS Eighty-seven consecutive patients ranging in age from 2 to 20 years. MEASUREMENTS The Cr-GFR was calculated by means of the formula GFR (milliliters per minute per 1.73 m2) = kL/serum creatinine (milligrams per deciliter), where L is body length in centimeters and k is a constant dependent on age and sex. Plasma clearance of technetium Tc 99m-labeled DTPA was our reference method for determination of GFR (DTPA-GFR). RESULTS The Cr-GFR formula identified children with impaired renal function (DTPA clearance, less than 80 mL/min per 1.73 m2) with a sensitivity of 95% and a specificity of 93%. In contrast, the sensitivity and specificity of elevated serum creatinine level for this purpose were 80% and 96%, respectively. Of the children with renal insufficiency (DTPA clearance, 40 to 79 mL/min per 1.73 m2), 91% were correctly identified by the Cr-GFR formula. However, only 65% of these children had elevated serum creatinine levels. Although all children with renal failure (DTPA clearance, less than 40 mL/min per 1.73 m2) had abnormally high serum creatinine levels, the specificity of this test was significantly lower than that of the Cr-GFR formula (75% vs 100%, respectively). CONCLUSIONS The Cr-GFR formula is superior to serum creatinine level for estimating GFR. This formula provides a simple, reasonably accurate screening test for the presence and severity of impaired renal function.
A phase I safety and pharmacokinetic (PK) study of recombinant Apo2L/TRAIL, an apoptosis-inducing protein in patients with advanced cancer.

3013 Background: Recombinant human Apo2L/TRAIL (rhApo2L) is the only dual pro-apoptotic receptor agonist that directly activates both pro-apoptotic receptors (DR4 & DR5). RhApo2L selectively induces apoptosis (programmed cell death) in a variety of cancer cells, while sparing most normal cells in preclinical models. RhApo2L is being co-developed by Genentech and Amgen as a targeted therapy for solid tumors and hematologic malignancies. The present study was designed to assess the safety and PK of intravenous rhApo2L administered for the first time to humans, comparing safety in patients with liver metastasis to those without. METHODS RhApo2L was administered to patients with advanced solid tumors or NHL for 5 consecutive days every three weeks up to 8 cycles at dose levels of 0.5, 1.5, 4, 8, and 15 mg/kg. Patients without liver metastasis were treated before patients with liver metastasis in a staggered fashion. RESULTS Fifty-one adult patients have currently been enrolled and treated through 15 mg/kg. Of 36 patients with available data, the most common diagnoses were colorectal, melanoma, lung, and ovarian cancers. After 586 administered doses, there were no dose-limiting toxicities or clearly attributable toxicities. Thirty-two patients had at least one post-baseline tumor assessment with 17 (53%) having stable disease, and 13 (41%) with progression. One patient with a chondrosarcoma had a confirmed, objective partial response at 8 mg/kg. No anti-Apo2L antibodies have been detected. PK results will be presented separately. CONCLUSIONS RhApo2L is safe and well tolerated up to 15 mg/kg. Enrollment is continuing at 8 mg/kg for expanded safety data and further dose optimization. Contribution to the standard treatment of advanced solid tumors and hematologic malignancies should be evaluated in randomized trials. [Table: see text].
12 Toxoplasmosis : Advances and Vaccine Perspectives

Toxoplasma gondii was first identified more than 100 years ago in the tissues of birds and mammals. In 1908 Nicolle and Manceoux described it for the first time in the gundi (Ctenodactylus gundi), a North African rodent, in tachyzoite forms. At the same time, Splendore in Brazil, identified the parasite in rabbit tissues. Due to its bow-like shape (Greek: Toxo = Arc) the genus was named Toxoplasma. However, only in the 1970’s was the complete life cycle known and the parasite recognized as a coccidian parasite (member of the phylum Apicomplexa). It is ubiquitous throughout the world and estimated to infect approximately half of the world's population. It is characterized by a polarized cell structure and two unique apical secretory organelles called micronemes and rhoptries. Toxoplasma has a complex life cycle consisting of a sexual cycle in its feline definitive hosts and an asexual cycle in its intermediate hosts. The latter, including humans, can be infected by ingestion of oocysts shed in cat feces. Unlike most other Apicomplexan parasites, Toxoplasma can be transmitted between intermediate hosts by either vertical (via placenta) or horizontal (carnivorism) transmission. Toxoplasma parasite is found in intermediate hosts in two interconvertable stages: bradyzoites and tachyzoites. Bradyzoites, a dormant form, are slow-growing, transmissible and encysted. Infections with bradyzoite-containing cysts occur upon ingestion of undercooked meat. The wall of these cysts is digested inside the host stomach and the released bradyzoites, which are resistant to gastric peptidases, subsequently invade the small intestine. There, they convert into tachyzoites, the rapidly growing, disease-causing form that can infect most nucleated cells, replicate inside a parasitophorous vacuole, egress, and then infect neighboring cells. These tachyzoites activate a potent host immune response that eliminates most of the parasites. Some tachyzoites, however, escape destruction and convert back into bradyzoites. In the absence of an adequate immune response, tachyzoites
Electrical remodeling in atrial fibrillation. Time course and mechanisms.

BACKGROUND Atrial fibrillation is self-perpetuating, suggesting that the tachyarrhythmia causes electrophysiological changes that contribute to the progressive nature of the disease. In animal models, pacing-induced rapid atrial rates result in sustained atrial fibrillation. This is mediated by shortening of refractory periods termed electrical remodeling. The purpose of the present study was to characterize the time course of electrical remodeling and to define mechanisms of the phenomenon. METHODS AND RESULTS Closed-chest dogs were anesthetized, pretreated with atropine and propranolol, and subjected to 7 hours of atrial pacing at 800 bpm. The effective and absolute refractory periods (ARP and ERP) were measured during and after rapid pacing, and transvenous endocardial biopsy specimens were examined using electron microscopy. Despite autonomic blockade and the absence of change in right atrial pressure, persistent atrial tachycardia caused ARP and ERP to fall by > 10%. Electrical remodeling developed quickly, with more than half of the phenomenon occurring during the first 30 minutes of high-rate pacing. Pretreatment with glibenclamide in doses sufficient to block the ATP-sensitive potassium current had no effect. Atrial electrical remodeling was blocked by verapamil and accentuated by hypercalcemia. Biopsy specimens from controls subjected to rapid pacing showed mitochondrial swelling consistent with calcium overload. Biopsies from verapamil-treated animals were normal. CONCLUSIONS Atrial electrical remodeling develops quickly, is progressive, and may be persistent. Shifts in autonomic tone, atrial stretch, or depletion of high-energy phosphates do not contribute significantly to the phenomenon. Results of the study suggest that atrial electrical remodeling is mediated by rate-induced intracellular calcium overload.
Role of protein degradation in the survival of carbon-starved Escherichia coli and Salmonella typhimurium

When an Escherichia coli K-12 culture was starved for glucose, 50% of the cells lost viability in about 6 days. When a K-12 mutant lacking five distinct peptidase activities, CM89, was starved in the same manner, viability was lost much more rapidly; 50% of the cells lost viability in about 2 days, whereas a parent strain lacking only one peptidase activity lost 50% viability in about 4 days. Compared with the wild-type strain and with its parent strain CM17, CM89 was defective in both protein degradation and protein synthesis during carbon starvation. Similar results were obtained with glucose-starved Salmonella typhimurium LT2 and LT2-derived mutants lacking various peptidase activities. An S. typhimurium mutant lacking four peptidases, TN852, which was deficient in both protein degradation and synthesis during carbon starvation (Yen et al., J. Mol. Biol. 143:21-33, 1980), was roughly one-third as stable as the isogenic wild type. Isogenic S. typhimurium strains that lacked various combinations of three of four peptidases and that displayed protein degradation and synthesis rates intermediate between those of LT2 and TN852 (Yen et al., J. Mol. Biol. 143:21-33, 1980) displayed corresponding stabilities during carbon starvation. These results point to a role for protein degradation in the survival of bacteria during starvation for carbon.
A randomized controlled trial of cognitive remediation among inpatients with persistent mental illness.

OBJECTIVE This study evaluated the feasibility and efficacy of a cognitive remediation program in improving cognitive and work functioning for intermediate- to long-stay psychiatric inpatients. METHODS Eighty-five inpatients with predominantly DSM-IV-defined schizophrenia were randomly assigned to cognitive remediation or to a control condition. The cognitive remediation program consisted of 24 hours of computerized practice over a 12-week period and a weekly discussion group to facilitate transfer of cognitive skills to daily activities. A computer control group received similar hours of staff and computer exposure without cognitive training exercises. A comprehensive neuropsychological battery was administered at baseline and posttreatment. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline, midtreatment (six weeks), and posttreatment (12 weeks) and at six- and 12-month follow-ups. Work functioning was tracked during a 12-month follow-up period. RESULTS The average number of 45-minute sessions completed was 23. Patients in the cognitive remediation group demonstrated significantly greater improvements over three months than the control group in the composite measure of overall cognitive functioning, psychomotor speed, and verbal learning. In addition, patients who received cognitive remediation worked more weeks than the control group over the 12-month follow-up period. Patients in both groups showed significant and comparable improvements over the follow-up period on the positive, activation, and depression subscales of the PANSS. CONCLUSIONS Cognitive remediation was a feasible treatment for this group of inpatients and more effective at improving cognitive functioning than a computer control intervention. Longer-term follow-up indicated that cognitive remediation was associated with better work outcomes, suggesting benefits in psychosocial functioning.
Proposta de recuperação de área degradada por queimadas no município de Marabá - PA

As acoes antropicas decorrentes do abrupto crescimento populacional no entorno de areas de protecao permanente – APP, resultam em diversas consequencias, como as queimadas. Por analisar os aspectos danosos dessa atividade, o objetivo dessa pesquisa foi elaborar uma proposta de recuperacao de area degradada em uma APP situada a margem direita do rio Itacaiunas, no municipio de Maraba - PA. O metodo aplicado foi dedutivo e a pesquisa foi de natureza aplicativa, e seguiu o protocolo estabelecido pelo Instituto Chico Mendes de Biodiversidade e Conservacao. O levantamento de dados documentais ocorreu com recorte temporal entre 2003 a 2017. Os dados indicaram que: (1) os valores para a acidez foram elevados (4,0 cmol c .dm 3 ); (2) houve diminuicao do teor de materia orgânica (1,4 dag. Kg), quando comparada com a area controle (MO = 2,1 dag. Kg); (3) reducao de concentracoes de Potassio (40 mg.dm -3 ; AC = 82 mg.dm -3 ) e Fosforo (1,0 mg.kg -3 ; AC = 10 mg.dm -3). Entretanto, noventa dias apos as queimadas, notou-se aspectos de regeneracao natural na regiao em relacao a vegetacao. Com isso, a proposta de recuperacao foi elaborada, e a tecnica de nucleacao, atraves do plantio de mudas, e o monitoramento a ser feito com o uso do sensoriamento remoto sao as medidas mais eficazes para a recuperacao da area pesquisada.
Self‐mutilation in antisocial personality (disorder)

In the present study, attempts were made to clarify the characteristics and the background information of persons with antisocial personality (disorder) who had resorted to slashings. These were compared with controls with a similar personality disorder who had not resorted to slashings. It appeared that the former had been more often prone to repeated outbursts of rage or fighting, drug abuse, and even other forms of self‐destruction as well as tattooing in prison. They had more often had an alcoholic father. Moreover, they were more withdrawn, anxious and had a tendency to blame their environment. They had more often made efforts to get out of the restricted milieu of prison to the prison's psychiatric department and experienced the confined space of the prison as oppressive. They resorted to slashing usually in prisons and it seemed that the restricted environment with an absence of sufficient stimuli was crucial in triggering self‐mutilation.
Molecular Effects of the Psychotropic NMDA Receptor Antagonist MK‐801 in the Rat Entorhinal Cortex: Increases in AP‐1 DNA Binding Activity and Expression of Fos and Jun Family Members

Abstract: Noncompetitive NMDA receptor antagonists such as phencyclidine and MK‐801 produce psychotropic symptoms that closely resemble schizophrenic psychosis and induce the expression of immediate early genes in limbic cortical areas. We are concentrating on analyzing molecular and physiological effects that these drugs produce in the entorhinal cortex and on the potential connection between these effects and the psychotic symptoms. We show here that MK‐801 increases the DNA binding activity of the activator protein‐1 (AP‐1) complex in the entorhinal cortex. We also observed increased expression of mRNAs for Fos and Jun transcription factor family members c‐Fos, FosB, Fra‐2, and JunB, as well as Fos family proteins in the entorhinal cortex after MK‐801 administration. This suggests that the activated AP‐1 complex consists of these transcription factors. Genes regulated by the AP‐1 complex in the entorhinal cortex might be involved in the pathophysiology of psychotic behavior and are potential targets for new antipsychotic drugs.
A novel strategy for myocardial protection using in vivo transfection of cis element 'decoy' against NFkappaB binding site: evidence for a role of NFkappaB in ischemia-reperfusion injury.

BACKGROUND NFkappaB, an important transcriptional factor, has been reported to play a significant role in the coordinated transcription of cytokine and adhesion molecule genes. Therefore, blocking the NFkappaB may attenuate ischemia reperfusion injury in the myocardium. For blocking transcriptional factors, gene therapy, such as cis element "decoy," appears to be an innovative and useful therapy. This study aimed to prove the efficacy of cis element decoy against NFkappaB binding site for myocardial protection. METHODS AND RESULTS Rat hearts were transfected with fluorescence isothiocyanate-labeled cis element decoy against NFkappaB (NF)-binding site (NF group, n=6) and scrambled decoy (SD) group (n=6) by coronary infusion of hemagglutinating virus of Japan (HVJ)-liposome during cardioplegic arrest. Both the NF and SD groups showed marked FITC-staining in the nuclei of myocytes, demonstrating the efficacy of gene transfer into the nuclei of cardiac myocytes as compared with the control group transfected with empty liposomes. After 3 days of transfection, the NF group showed significantly higher percentages of recovery of left ventricular developed pressure (NF versus SD, 87+/-11 versus 54+/-12%) and coronary flow (97+/-16 versus 61+/-15%) than did the control hearts when exposed to ischemia (30 minutes, 37 degrees C) and reperfusion (30 minutes, 37 degrees C). The NF group showed a significantly lower percentage of neutrophil adherence to endothelial cells (38+/-6 versus 81+/-3%) and a lower tissue level of interleukin-8 (109+/-48 versus 210+/-55 ng/mg) than did the SD group. CONCLUSION The hearts transfected with cis element decoy against NFkappaB binding site showed significant improvement in tolerance against ischemia-reperfusion injury in association with the inhibition of neutrophil adherence and tissue IL-8 production. This suggests that NFkappaB plays a significant role in ischemia-reperfusion injury. This method, using in vivo gene transfection of cis element decoy against NFkappaB binding site, appears to be a novel and future strategy for myocardial protection.
Janus kinase 2 modulates the lipid-removing but not protein-stabilizing interactions of amphipathic helices with ABCA1 Published, JLR Papers in Press, October 6, 2005.

ABCA1 mediates the transport of cellular cholesterol and phospholipids to HDL apolipoproteins. Apolipoprotein A-I (apoA-I) interactions with ABCA1-expressing cells elicit several responses, including removing cellular lipids, stabilizing ABCA1 protein, and activating Janus kinase 2 (JAK2). Here, we used synthetic apolipoprotein-mimetic peptides to characterize the relationship between these responses. Peptides containing one amphipathic helix of l- or d-amino acids (2F, D-2F, or 4F) and a peptide containing two helices (37pA) all promoted ABCA1-dependent cholesterol efflux, competed for apoA-I binding to ABCA1-expressing cells, blocked covalent cross-linking of apoA-I to ABCA1, and inhibited ABCA1 degradation. 37pA was cross-linked to ABCA1, confirming the direct binding of amphipathic helices to ABCA1. 2F, 4F, 37pA, and D-37pA all stimulated JAK2 autophosphorylation. Inhibition of JAK2 greatly reduced peptide-mediated cholesterol efflux, peptide binding to ABCA1-expressing cells, and peptide cross-linking to ABCA1, indicating that these processes require an active JAK2. In contrast, apoA-I and peptides stabilized ABCA1 protein even in the absence of an active JAK2, implying that this process is independent of JAK2 and lipid efflux-promoting binding of amphipathic helices to ABCA1. These findings show that amphipathic helices coordinate the activity of ABCA1 by several distinct mechanisms that are likely to involve different cell surface binding sites.
The SPARC DynVar Project: A SPARC Project on the Dynamics and Variability of the Coupled Stratosphere-Troposphere

P. J. Kushner, University of Toronto, Canada (paul.kushner@utoronto.ca) J. Austin, NOAA GFDL, USA (John.Austin@noaa.gov) M. P. Baldwin, NWRA, USA (mark@nwra.com) N. Butchart, UK Met Office, UK (neal.butchart@metoffice.gov.uk) M. A. Giorgetta, MPI for Meteorology, Germany (marco.giorgetta@zmaw.de) P. H. Haynes, DAMTP, University of Cambridge, UK (P.H.Haynes@damtp.cam.ac.uk) E. Manzini, CMCC/INGV, Italy (manzini@bo.ingv.it) N. A. McFarlane, SPARC IPO, Canada (norm.mcfarlane@ec.gc.ca) A. O’Neill, University of Reading, UK (alan@met.reading.ac.uk) J. Perlwitz, University of Colorado, USA (judith.perlwitz@noaa.gov) L. M. Polvani, APAM and EESC, Columbia University, USA (lmp@columbia.edu) W. A. Robinson, NSF, USA (robinson@atmos.uiuc.edu) F. Sassi, NCAR, USA (sassi@ucar.edu) J. F. Scinocca, CCCma, Canada (john.scinocca@ec.gc.ca) T. G. Shepherd, University of Toronto, Canada (tgs@atmosp.physics.utoronto.ca)
Neuroprotective effect of Perilla extracts on PC12 cells

Background: Perilla frutescens (L) Britton contains some active principles which had neuroprotective actions. Objective: The present study was aimed to investigate the effect of Perilla extracts on neuroprotection, antioxidation and neurite outgrowth in PC12 cells. Material and Method: The neuroprotective effect of freeze-dried ethanolic extract from Perilla leaves and cold-pressed seed oil were tested on PC12 induced with beta-amyloid protein. The inhibition of tau-protein hyperphosphorylation and the antioxidant enzyme activity were analyzed. The neurite outgrowth bearing cells were investigated and MEK-1 protein production was analyzed by enzyme immunometric assay. Results: In PC12 culture induced toxicity by beta-amyloid protein: (1) the decrease in cell viability was attenuated in cells pretreated with leaf extract 200 mg/ml and oil 50 mg/ml; (2) SOD activity seemed to decrease when pretreated cells with the extracts; (3) tau phosphorylation was decreased by pretreated cells with50 mg/ml of oil. Moreover, given Perilla leaf extract or seed oil to PC12 culture, the amount of neurite outgrowth bearing cells increased harmoniously with MEK-1 protein expression. Conclusion: Perilla leaf extract and seed oil reversed the effect of beta-amyloid induced toxicity by decreasing oxidative stress and inhibition of tau-protein hyperphosphorylation. The enhancement of neurite outgrowth by Perilla extracts was also revealed.