Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of the Pharmacokinetics, Pharmacodynamics, and Safety of Oral (Catapres) and Transdermal (M‐5041T) Clonidine in Healthy Subjects

The pharmacokinetic as well as pharmacodynamic properties of a transdermal clonidine, M‐5041T (M) and its safety were compared with those of oral clonidine, Catapres (Nippon Boehringer Ingelheim, Hyogo, Japan). One patch of M containing 6 mg of clonidine was applied on the right chest for 3 days or one tablet of Catapres (.075 mg) was given orally every 12 hours for 3 days in eight healthy subjects. The study was conducted by a crossover design with 14 to 16 days' interval between the cross‐over. Blood and urine samples for clonidine concentration were obtained, and blood pressure (BP) was measured for a 168‐hour period after application of M and for a 96‐hour period after initiation of Catapres therapy. Plasma concentration of clonidine increased gradually after application of M and decreased gradually after removal, whereas this parameter increased rapidly during the absorption phase and decreased rapidly in the elimination phase after each dosage of Catapres. Elimination half‐life of clonidine after removal of M was significantly greater than that after the final dosage of Catapres. No significant difference was observed in maximum plasma concentration or area under the plasma concentration ‐time curve between the two trials. The BP lowering effects of M and Catapres did not differ significantly. Adverse symptoms occurred more frequently during Catapres therapy than during treatment with M. Most of these symptoms were observed when plasma clonidine concentration was relatively higher in each trial. These results suggest that M is effective for the treatment of hypertension with a lower incidence of adverse symptoms. Because the current study was nonblind and involved small number of subjects, however, a large controlled study is needed to evaluate its safety further.
Anatomical characteristics of tonic and phasic postganglionic neurons in guinea pig bronchial parasympathetic ganglia

Anatomical characteristics of principal parasympathetic ganglia neurons on the guinea pig primary bronchus were analyzed, and the procedure for localizing the ganglia without the aid of staining for in vitro physiological studies is described. The neurons were tightly packed within a perineural sheath, and the cell bodies formed a homogeneous population based on size and shape. By using intracellular electrophysiological recordings, unstained neurons within these ganglia were characterized with suprathreshold depolarizing stimuli as having either accommodating action potential patterns (phasic neurons) or repetitive action potential patterns (tonic neurons). After determining whether a cell was tonic or phasic, it was injected with either horseradish peroxidase or Neurobiotin for characterization of its dendrites. There were no differences between tonic and phasic neurons, and both exhibited the following: (1) dendrites were multiple and branching; (2) all processes (axon and dendrites) arose from a circumscribed area on the somatic surface; (3) the initial direction of the processes was usually toward the center of the ganglion, creating a very dense intraganglionic neuropil; (4) tapering processes (presumed dendrites) extended beyond the border of the perineural sheath; and (5) many processes terminated with bouton‐like swellings near the somatic surfaces of neighboring neurons within the same ganglion. Electron microscopic examination of dendritic and cell body membranes revealed that greater than 90% of the synapses occurred on dendrites. Based on immunohistochemical staining, all neurons were calbindin negative. These results indicate a relatively homogeneous population of neurons in bronchial parasympathetic ganglia displaying dendritic characteristics compatible with complex integrative properties. J. Comp. Neurol. 419:439–450, 2000. © 2000 Wiley‐Liss, Inc.
Differential effects of cyclosporin and tacrolimus on the expression of fibrosis‐associated genes in isolated glomeruli from renal transplants

Chronic allograft nephropathy is characterized by an excessive accumulation of extracellular matrix proteins leading to glomerular and interstitial fibrosis. The aim of this study was to determine the effects of two different immunosuppressive agents (cyclosporin and tacrolimus) on the expression of the genes controlling extracellular matrix deposition in renal transplant glomeruli.
Identification of appropriate housekeeping genes for quantitative RT-PCR analysis in MDA-MB-231 and NCI-H460 human cancer cell lines under hypoxia and serum deprivation

This work was supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [grant agreement No. 88881.132780/2016-01]; Fundac ao de Amparoa Ciencia e Tecnologia de Pernambuco (FACEPE) [grant agreement No. 0883-2.08/13];and the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie [grant agreement No. 748880]. This work was also funded by the project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); and by FEDER—Fundo Europeu de Desenvolvimento Regional funds through COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020,and by Portuguese funds through FCT (Fundacao para a Ciencia e a Tecnologia)/Ministerio da Ciencia, Tecnologia e Inovacao in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274), and the project POCI-01-0145-FEDER-016585 (PTDC/BBB EBI/0567/2014).
Primary cardiac tumors: early and late results of surgical treatment in 91 patients.

BACKGROUND Between March 1980 and September 1997, 91 patients underwent evaluation and treatment for primary cardiac neoplasms. METHODS Tumors were grouped into three categories: atrial myxomas, benign nonmyxomas, and malignant tumors. Survivors were contacted; no one was lost to follow-up. The mean follow-up for this series is 7 +/- 5 years. RESULTS Eighty-three patients were diagnosed with atrial myxomas (Male/Female: 29/54), average age 55 +/- 13 years. The hospital mortality was 3.6% (3/83), the late mortality was 6.5% (5/80). No recurrent myxomas have been identified clinically or by echocardiography in any patient. Three patients were diagnosed with benign nonmyxoma tumors. (Male/Female: 2/1), average age 64 +/- 8 years. There were no perioperative deaths and 1 patient died 4 years postoperatively from fibroma, with no linked causes. No recurrent tumors have been identified. Five patients were diagnosed with malignant tumors. (M/F: 1/4), average age 53 +/- 16 years. The hospital mortality was 20% (1/5); in 3 patients a redo-operation was necessary after 8, 11, and 12 months because of tumor recurrence. All patients died within 3 years of the first operation (mean 13 +/- 14 months). CONCLUSIONS Surgical resection, when possible, is the treatment of choice for all primary cardiac tumors. Patients with benign tumors are probably cured by resection and in our experience there was no known tumor recurrence. Effective palliation is possible with resection of malignant tumors, but more effective adjuvant therapy will be necessary to improve long-term prognosis.
Effect of Rds abundance on cone outer segment morphogenesis, photoreceptor gene expression, and outer limiting membrane integrity

We examined the molecular, structural, and functional consequences on cone photoreceptors of the neural retinal leucine zipper knockout (Nrl−/−) mice when only one allele of retinal degeneration slow (Rds) is present (Rds+/−/Nrl−/−). Quantitative RT‐PCR and immunoblot analysis were used to assess the expression levels of several phototransduction genes; electroretinography was used to assess quantitatively the retinal responsiveness to light; and immunohistochemistry and ultrastructural analysis were used to examine retinal protein distribution and morphology, respectively. In Rds/Nrl double‐null mice, S‐cones form dysmorphic outer segments that lack lamellae and fail to associate properly with the cone matrix sheath and the outer limiting membrane. In Rds+/−/Nrl−/− mice, cones form oversized and disorganized outer segment lamellae; although outer limiting membrane associations are maintained, normal interactions with cone matrix sheaths are not, and photoreceptor rosette formation is observed. These retinas produce significantly higher photopic a‐wave and b‐wave amplitudes than do those of Rds−/−/Nrl−/− mice, and the levels of several cone phototransduction genes are significantly increased coincidently with the presence of Rds and partial lamellae formation. Thus, as in rod photoreceptors, expression of only one Rds allele is unable to support normal outer segment morphogenesis in cones. However, cone lamellae assembly, albeit disorganized, concomitantly permits outer limiting membrane association, and this appears to be linked to photoreceptor rosette formation in the rodless (cone‐only) Nrl−/− retina. In addition, photoreceptor gene expression alterations occur in parallel with changes in Rds levels. J. Comp. Neurol. 504:619–630, 2007. © 2007 Wiley‐Liss, Inc.
Axillary Meristem Formation in Rice Requires the WUSCHEL Ortholog TILLERS ABSENT1[OPEN]

A WOX gene, TAB1/WUS, plays a critical role in the initiation of the axillary meristem development in rice. Axillary shoot formation is a key determinant of plant architecture. Formation of the axillary shoot is regulated by initiation of the axillary meristem or outgrowth of the axillary bud. Here, we show that rice (Oryza sativa) TILLERS ABSENT1 (TAB1; also known as Os WUS), an ortholog of Arabidopsis thaliana WUS, is required to initiate axillary meristem development. We found that formation of the axillary meristem in rice proceeds via a transient state, which we term the premeristem, characterized by the expression of OSH1, a marker of indeterminate cells in the shoot apical meristem. In the tab1-1 (wus-1) mutant, however, formation of the axillary meristem is arrested at various stages of the premeristem zone, and OSH1 expression is highly reduced. TAB1/WUS is expressed in the premeristem zone, where it shows a partially overlapping pattern with OSH1. It is likely, therefore, that TAB1 plays an important role in maintaining the premeristem zone and in promoting the formation of the axillary meristem by promoting OSH1 expression. Temporal expression patterns of WUSCHEL-RELATED HOMEOBOX4 (WOX4) indicate that WOX4 is likely to regulate meristem maintenance instead of TAB1 after establishment of the axillary meristem. Lastly, we show that the prophyll, the first leaf in the secondary axis, is formed from the premeristem zone and not from the axillary meristem.
ETA Receptor Blockade Decreases Vascular Superoxide Generation in DOCA-Salt Hypertension

Abstract—Development and progression of end-organ damage in hypertension have been associated with increased oxidative stress. Superoxide anion accumulation has been reported in deoxycorticosterone acetate (DOCA)-salt hypertension, in which endothelin-1 plays an important role in cardiovascular damage. We hypothesized that blockade of ETA receptors in DOCA-salt rats would decrease oxidative stress. Both systolic blood pressure (SBP, 210±9 mm Hg; P <0.05) and vascular superoxide generation in vivo were increased in DOCA-salt (44.9±10.3% of ethidium bromide–positive nuclei; P <0.05) versus control uninephrectomized (UniNx) rats (118±3 mm Hg; 18.5±3%, respectively). In DOCA-salt rats, the ETA antagonist BMS 182874 (40 mg/kg per day PO) lowered SBP (170±4 versus UniNx, 120±3 mm Hg) and normalized superoxide production (21.7±6 versus UniNx, 11.9±7%). Vitamin E (200 mg/kg per day PO) decreased superoxide formation in DOCA-salt rats (18.8±7%) but did not alter SBP. Oxidative stress in nonstimulated circulating polymorphonuclear cells (PMNs) or in PMNs treated with zymosan, an inducer of superoxide release, was similar in DOCA-salt and UniNx groups. Superoxide formation by PMNs was unaffected by treatment with BMS 182874. Western blot analysis showed increased nitrotyrosine-containing proteins in mesenteric vessels from DOCA-salt compared with UniNX. Treatment with either BMS 182874 or vitamin E abolished the differences in vascular nitrotyrosine-containing proteins between DOCA-salt and UniNX. Maximal relaxation to acetylcholine was decreased in DOCA-salt aortas (75.8±4.2% versus UniNx, 95.4±1.9%, P <0.05). BMS 182874 treatment increased acetylcholine-induced relaxation in DOCA-salt aortas to 93.5±4.5%. These in vivo findings indicate that increased vascular superoxide production is associated with activation of the endothelin system through ETA receptors in DOCA-salt hypertension, in apparently blood pressure–independent fashion.
When are Firms Sued for Qualitative Disclosures? Implications of the Safe Harbor for Forward-Looking Statements

Prior research finds that positive tone in firms' qualitative disclosures increases the risk of shareholder lawsuits. However, federal securities laws provide a safe harbor intended to shield firms' forward-looking statements from legal liability. One implication of this safe harbor is that litigation risk potentially varies between qualitative forward- and non-forward-looking statements. Consistent with this implication, we find that positive tone in forward-looking qualitative statements is significantly less related to the likelihood of subsequent litigation than is positive tone in non-forward-looking qualitative statements. On average, we fail to find a significant association between qualitative forward-looking statements and subsequent litigation. We do find evidence, however, that positive tone in qualitative forward-looking statements relates positively to subsequent litigation in two U.S. circuits in which court rulings reduced safe harbor protections for forward-looking statements. Overall, our results are consistent with the safe harbor effectively shielding firms' qualitative forward-looking statements from litigation risk.
Are high-fit CSR programs always better? The effects of corporate reputation and CSR fit on stakeholder responses

Purpose The purpose of this paper is to examine how corporate reputation interacts with corporate social responsibility (CSR) fit and affects stakeholders’ skeptical attribution (SA) of CSR motives, as well as their attitudes, supportive communication intent and purchase intent. This study proposes that a high-fit CSR program does not necessarily engender more favorable outcomes, nor does it stimulate SA. The study proposes the effects of CSR fit differ by corporate reputation. For bad-reputation companies, low-fit is anticipated to generate more desirable CSR outcomes than high-fit initiatives. Design/methodology/approach Two experiments were conducted. The first experiment employed a randomized 2 (CSR fit: high fit vs low fit) × 2 (good reputation vs bad reputation) × 2 (Industry: food retailing and insurance) full factorial design to examine the suggested hypotheses. The second study employed a randomized 2 (CSR fit: high fit vs low fit) × 2 (good reputation vs bad reputation) full factorial design with consumer samples to replicate the conceptual relationships among variables in the first study. Findings While reputation plays a dominant role in influencing stakeholders’ CSR-related responses across both CSR fit situations, a SA partially mediates the relationship between reputation and stakeholder reactions. CSR fit interacts with reputation, and influences the partial mediation process through SA; under a bad reputation condition, low-fit CSR engenders less SA and results in better stakeholder reactions. A similar tendency was found with supportive communication intent and purchase intent. High-fit CSR initiatives by a negative reputation company engendered the weakest supportive intent and purchase intent. For a reputable company, across both CSR fits, respondents displayed generally very positive attitudes toward, greater intent to support, and intent to purchase from the company. Originality/value The study findings provide useful and empirically supported logical explanations of why high-fit CSR programs sometimes cause backlash effects, despite the general consensus that such initiatives generate positive outcomes. This study offers an alternative and more relevant perspective to conceptualize the complexity of anticipating CSR outcomes.
Censorship, Family Planning, and the Historical Fertility Transition

The historical fertility transition is one of the most important events in economic history. This study provides new evidence on the role that ideas about family planning played in this transition. We begin by documenting a link between the famous Bradlaugh-Besant trial that took place in England in 1877, which revolved around the morality of family planning, and the sharp decline in fertility that took place in Britain beginning in that year. We then show that similar declines are observed among populations living outside of Britain but with strong cultural and linguistic links to Britain. Our findings highlight the importance of changing social norms in the historical fertility transition and provide novel evidence showing that cultural and linguistic ties can play an important role in rapidly transmitting social change around the world.
Calcium in the mechanism of ammonia‐induced astrocyte swelling

Brain edema, due largely to astrocyte swelling, is an important clinical problem in patients with acute liver failure. While mechanisms underlying astrocyte swelling in this condition are not fully understood, ammonia and associated oxidative/nitrosative stress appear to be involved. Mechanisms responsible for the increase in reactive oxygen/nitrogen species (RONS) and their role in ammonia‐induced astrocyte swelling, however, are poorly understood. Recent studies have demonstrated a transient increase in intracellular Ca2+ in cultured astrocytes exposed to ammonia. As Ca2+ is a known inducer of RONS, we investigated potential mechanisms by which Ca2+ may be responsible for the production of RONS and cell swelling in cultured astrocytes after treatment with ammonia. Exposure of cultured astrocytes to ammonia (5 mM) increased the formation of free radicals, including nitric oxide, and such increase was significantly diminished by treatment with the Ca2+ chelator 1,2‐bis‐(o‐aminophenoxy)‐ethane‐N,N,‐N′,N′‐tetraacetic acid tetraacetoxy‐methyl ester (BAPTA). We then examined the activity of Ca2+‐dependent enzymes that are known to generate RONS and found that ammonia significantly increased the activities of NADPH oxidase (NOX), constitutive nitric oxide synthase (cNOS), and phospholipase A2 (PLA2) and such increases in activity were significantly diminished by BAPTA. Pre‐treatment of cultures with 7‐nitroindazole, apocyanin, and quinacrine, respective inhibitors of cNOS, NOX, and PLA2, all significantly diminished RONS production. Additionally, treatment of cultures with BAPTA or with inhibitors of cNOS, NOX, and PLA2 reduced ammonia‐induced astrocyte swelling. These studies suggest that the ammonia‐induced rise in intracellular Ca2+ activates free radical producing enzymes that ultimately contribute to the mechanism of astrocyte swelling.
[Involvement of endogenous opioids in cardioprotective effects of ischemic preconditioning in the isolated rat heart].

In the present study, the relationship between the blockade of kappa-opioid receptor and ischemic preconditioning (IP) was examined and the effect of IP and prolonged ischemia on levels of dynorphin A1-13 (Dyn A1-13) in cardiac muscle in isolated perfused rat heart was investigated. The results are as follows: (1) IP reduced the severity of ischemia/reperfusion arrhythmia (P < 0.05) and infarct size (P < 0.01), but had no significant effect on heart rate and coronary flow (P > 0.05); (2) MR2266, kappa opioid receptor antagonist, reduced the severity of ischemia/reperfusion arrhythmia (P < 0.05) and infarct size (P < 0.01), and also enhanced the recovery of coronary flow, but had no significant effect on heart rate (P > 0.05); and (3) prolonged ischemia decreased the levels of Dyn A1-13 (P < 0.05), which was more marked in the unpreconditioned hearts. The results suggest: (1) MR2266 can "mimic" cardioprotective effect of IP in reducing the severity of arrhythmias and limiting infarct size of cardiac muscle; (2) ischemia causes release of endogenous kappa opioids, which can be attenuated by IP; and (3) the cardioprotective effects of IP in rat heart involves endogenous kappa opioids.
Superstar Exporters: An Empirical Investigation of Strategic Interactions in Danish Export Markets

Abstract In many countries, exports are highly concentrated among a few “superstar” firms. We estimate the export decisions of superstar firms as the result of a complete information, simultaneous, discrete choice, static entry game. We employ a dataset on the universe of Danish trade transactions by firm, product and destination. We also obtain detailed information on applied, preferential tariff protection from the MAcMap-HS6 database. We find evidence of strong negative competitive effects of entry: in the absence of strategic competitive effects, firms would be 53.2 percentage points more likely to export to a given market. Next, we run two counterfactual exercises. We show that failing to account for the strategic interaction among superstar exporters leads to: (i) overstating the probability that firms would start exporting to a market following tariff elimination by a factor of two; and, (ii) overstating the probability that firms would stop exporting to a market if tariffs were imposed by a factor of more than five.
Comparison of Natural Product Use Between Primary Care and Nephrology Patients

BACKGROUND: The use of natural products is increasing, but healthcare professionals may underestimate the use of these agents by patients. It is unknown whether natural product use differs between primary care and specialty clinic patients, such as those in a nephrology clinic. OBJECTIVE: To compare patterns of natural product use between primary care and nephrology clinic patients. METHODS: One thousand adult patients from each clinic were randomly mailed an anonymous questionnaire to determine current and past use of natural products. RESULTS: A total of 491 surveys were returned, for an overall response rate of 26% (25% primary care; 28% nephrology clinic). Current use of natural products was similar between the primary care and nephrology groups (34% vs 29%, respectively; p = NS). Primary care patients were more likely to have taken a natural product in the past (57% vs 45%; p < 0.05); Echinacea was the most common product taken by those patients (26%). Green tea was the most common natural product taken by nephrology clinic patients (18%). More primary care patients took Echinacea compared with nephrology clinic patients (26% vs 12%; p < 0.01). Adverse reactions led to discontinuation of the natural product in 7% of respondents. CONCLUSIONS: Active use of natural products was similar between the survey respondents. Documentation and monitoring of natural product use by healthcare professionals working with primary care and nephrology clinic patients are recommended.