Compensatory State Research Articles

Expression of thyroid-specific transcription factors in thyroid carcinoma, contralateral thyroid lobe and healthy thyroid gland in dogs

Thyrotropin receptor (TSH-R), thyroglobulin (Tg), thyroperoxidase (TPO), thyroid specific transcription factor-1 (TTF-1), paired box 8 transcription factor (PAX-8), insulin like growth factor-1 (IGF-1) and estrogen receptor alpha (ERα) transcripts were determined by real-time PCR in follicular carcinoma and contralateral (CL) lobes, and healthy thyroid canine glands. Concentrations of TSH-R, PAX-8, and ERα mRNA were not different among groups; the carcinoma group had lower Tg and TPO mRNA than healthy and CL groups, while no differences were found between the two latter groups, suggesting that the carcinoma tissue presents an altered capacity to synthesize thyroid hormones. The transcription factor that promotes thyrocytes proliferation, TTF-1 as well as IGF-1, presented a greater mRNA expression in the CL group, suggesting that the CL lobe may function in a compensatory state.

Welfare Spending in an Era of Globalization: The North—South Divide

This paper examines the assertion that economic globalization has led to the decline of welfare spending in recent decades. Although it is often argued that the increasing intensity of globalization has led to such a decline in the industrialized states, the paper finds that there has been little, if any, downturn in either levels of state expenditure in general or in levels of welfare spending in particular. However, the experience of the developing states has been rather different. In their case, the last few decades indicate that stagnation or a decline in welfare spending has occurred, particularly during the period of structural adjustment implementation. It is argued that the OECD countries still manage to provide a high level of social welfare to their populations that closely resembles the compensatory state model. In contradistinction, many of the states in the South have struggled to maintain their levels of social expenditure and therefore most resemble Cerny's competitive state model. In order to explain these two divergent outcomes, the paper examines the way in which the behaviour of certain key international financial actors (investors, multinational companies, international financial institutions) differs with regard to these two sets of countries.

EFFECTS OF LIVER FIBROSIS ON VERAPAMIL PHARMACOKINETICS IN RATS

1. Liver fibrosis is the compensatory state of cirrhosis. In the long asymptomatic period, it is imperative to select a proper dosing regimen for drugs that are applicable to hepatic fibrosis owing to altered pharmacokinetics and bioavailability. The present study was designed to observe the changes in verapamil pharmacokinetics in rats with early liver fibrosis with respect to alterations in cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp). 2. A rat liver fibrosis model was successfully established using several inducers, including a high-fat diet, alcohol and carbon tetrachloride. After rats received a single intravenous or oral dose of verapamil (5 mg/kg), the plasma concentrations of verapamil were determined at scheduled time-points using HPLC. The activity of hepatic and small intestinal microsomal erythromycin N-demethylase (a marker for CYP3A) and the expression of small intestinal cyp3a and multidrug resistance (mdr) mRNA were compared between normal rats and rats with liver fibrosis. 3. The results showed that when verapamil was administered intravenously, the area under the curve (AUC), elimination half-life (T((1/2)(K10))) and mean residence time (MRT) increased significantly, whereas clearance (Cl) decreased, in rats with liver fibrosis compared with normal rats. After oral administration of verapamil, the AUC, (T((1/2)(K10))) and maximum concentration (C(max)) increased, Cl decreased and the absorption half-life (T((1/2)(K01))) and time to peak concentration (T(max)) were unchanged compared with normal rats. The oral bioavailability of verapamil was 32.9% in normal rats and 34.4% in rats with liver fibrosis. Furthermore, decreased CYP3A activity in the liver was accompanied by upregulated cyp3a9/18 and unchanged mdr mRNA in the small intestine compared with normal rats. Expression of cyp3a9/18 and mdr mRNA in the intestine was significantly inhibited by verapamil. 4. The results suggest that the lowered Cl and increased AUC of verapamil after intravenous and oral administration in rats with liver fibrosis were due to downregulation of CYP3A in the liver. The absorption rate of verapamil in rats with liver fibrosis was unchanged because mdr was unchanged and cyp3a was inhibited in the intestine by verapamil itself. There was no notable difference in oral bioavailability between normal rats and rats with liver fibrosis.

ESTABLISHMENT OF RAT PRECISION‐CUT FIBROTIC LIVER SLICE TECHNIQUE AND ITS APPLICATION IN VERAPAMIL METABOLISM

1. Liver fibrosis is the compensatory state of cirrhosis. In the long asymptomatic period, it is imperative to select a proper dosing regimen for drugs that are applicable to hepatic fibrosis. Otherwise, progressive deterioration to uncompensated cirrhosis may occur. The present study explored the characteristics of drug metabolism in fibrotic liver. 2. A rat precision-cut fibrotic liver slice (PCFLS) technique was established and the metabolism of verapamil was studied employing this technique. A rat hepatic fibrosis model was successfully induced integrating complex factors that included a high-fat diet, alcohol and CCl4. The PCFLS were incubated under different conditions and lactate dehydrogenase leakage, glutathione S-transferase activity and 3[4,5-dimethythiazole-2-yl]-2,5-diphenyltetrazolium bromide reduction were used as indices to assess PCFLS viability. Activities of phase I and phase II metabolizing enzymes were monitored following treatment with cytochrome P450 (CYP) inducers. Normal and fibrotic liver slices were incubated individually with 10 micromol/L verapamil. The concentration of verapamil in the medium was determined by high-performance liquid chromatography and intrinsic clearance (Cl(int)) was calculated on the basis of the concentration-time curve. 3. The results showed that the PCFLS viability remained steady throughout the 6 h of culture when the thickness of slices was 300 microm and pH of the medium was 7.0; CYP inducers (phenobarbital and ethanol) enhanced CYP2E1, CYP3A1/2 and uridine diphosphate-glucuronate transferase (UDPGT) activities, respectively, in a time-dependent manner. The Cl(int) (microL/min per mg) values differed significantly between normal (9.7 +/- 1.8) and fibrotic (5.6 +/- 1.4) liver slices (P < 0.01). 4. These results suggested that the PCFLS could remain viable for 2-6 h under appropriate conditions. The stability and inducibility of drug-metabolizing enzymes of PCFLS were also demonstrated. Furthermore, the metabolic rate of verapamil in PCFLS was decreased. These findings add further support to the use of PCFLS as a tool to study drug metabolism and to guide clinical medication.

Basic Autonomic Nervous Function in Patients with Neurocardiogenic Syncope

Basic autonomic nervous function was evaluated in patients with neurocardiogenic syncope (NCS). Atropine, isoproterenol, propranolol, phenylephrine, and phentolamine were administered successively, and parasympathetic nerve activity and β- (and α-) activity, sensitivity, and secretion of the sympathetic nerve were determined in patients with NCS and control subjects. In patients with NCS, β- and α- sensitivity were higher and β-activity and β- and α-secretion lower than in control subjects.In patients with NCS, the increased basic β-sensitivity may contribute to induce strong cardiac contractions and augment ventricular mechanoreceptor response, and a compensatory state against diminished neuronal sympathetic activity is suggested by the increased α-sensitivity.

Calcineurin and matrix protein expression in cardiac hypertrophy

In the compensatory state of human left ventricular hypertrophy (LVH), the remodeling processes in the extracellular matrix and the role of calcineurin (Cn) are not completely understood. The present work aimed to analyze the expression and activity of matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and of Cn in patients with compensated LVH. By semiquantitative RT-PCR, Western blotting, and gelatine zymography, we determined mRNA, protein, and/or enzyme activity levels of MMPs, TIMPs, atrial natriuretic peptide (ANP), Cn subunits, and of the modulatory calcineurin-interacting protein (MCIP) 1. Myocardial samples from patients showing severe aortic stenosis, normal ejection fraction, and compensated LVH were compared with autopsy samples from healthy hearts. LVH patients showed upregulation of CnA-beta mRNA but downregulation of both CnB-alpha mRNA and protein. Total Cn activity (as determined through NF-AT phosphorylation and MCIP1 mRNA expression) was unchanged. There were no differences in gene expression and activities of MMP-2, MMP-9, and of TIMPs 1-4 between LVH patients and controls. As expected, ANP mRNA expression was high in LVH patients. We propose a prominent role for CnB in controlling Cn activity in compensated LVH. At this stage of the disease, MMP and TIMP activities are balanced.

Mouse Pneumonia Model of Sickle Cell Acute Chest Syndrome.

Increased pulmonary inflammation in response to bacterial pneumonia may underlie the pathogenesis and lethality of the acute chest syndrome (ACS) in patients with sickle cell disease (SCD). Although transgenic mice expressing exclusively human sickle hemoglobin are gaining wide use as models of severe SCD, due to their similarities to human SCD-SS (i.e., severe hemolytic anemia, sickle deformation, microvascular occlusion, and multi-organ infarcts; Pastzy 1997 Science 278:876), their applicability for the investigation of ACS has not been tested. Currently, there is no animal model of sickle ACS other than acute hypoxic death, which is not a clinically relevant scenario. HYPOTHESIS: SCD is associated with an extreme compensatory state that depletes anti-oxidant and endothelial functional reserves and results in a heightened susceptibility to physiologic challenges. We hypothesized that, similar to human SCD-SS, these transgenic mice would exhibit an increased sensitivity to the lethal effects of intrapulmonary bacterial challenge. METHODS: Age- and sex-matched SS mice and hemizygote colony controls were raised in pathogen-free breeding colonies. Randomly selected animals at baseline had lung histology and micro-computed tomography (CT) performed. E. coli was selected for intrapulmonary bacterial inoculation to avoid the confounding issues of immunologic susceptibility to encapsulated bacteria in SCD. Using isoflurane anesthesia and orotracheal intubation, E. coli was inoculated in low (0.15 x 10 9 CFU/kg) or high (0.6 x 109 CFU/kg) doses, each in 50 mcl saline. Following E. coli inoculation all mice were treated with fluids on day 1 and antibiotics on day 1 to day 4, and were observed until day 7. RESULTS: On lung histology at baseline, SS mice showed greater vascular congestion and capillary dilation than control mice (mean scores ± SD) and increased circulating neutrophils (mean cells/HPF ±SD) (6.0±0 vs 2.5±2.4, 5.5±0.6 vs 1.0±0.8, and 3.5±1.7 vs 0.8±0.5 respectively, all p<0.05). Findings on lung micro CT were consistent with these differences. Low dose E. coli was nonlethal in both controls and SS mice (n=5, respectively). With high doses of E. coli, although overall mortality rate at day 7 was greater in SS mice than in controls (7 of 10 SS died vs 6 of 10 controls) this was not significant ( p=ns). However, compared to control nonsurvivors, the time to death (mean ±SD) in SS nonsurvivors was shorter (52±47 vs 88±29, p=0.15). Furthermore, by 48 h although all controls were still alive, 3 of 10 SS mice had already died (p=0.004 by Chi-square, uncorrected). Micro CT showed patchy consolidation of lungs. DISCUSSION: Thus this transgenic mouse model of SCD was associated with baseline pulmonary changes on histology and micro CT and increased sensitivity to the lethal effects of intrapulmonary bacterial challenge, changes consistent with those observed clinically. The lethality difference between low- and high-dose E. coli demonstrates that the susceptibility of SS mice is not to the invasive procedures, but to the physiologic challenge of the infection. The present findings suggest that this mouse model of SCD and pneumonia should be explored further as a tool to investigate the pathogenesis and treatment of ACS.

From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of the Modern Order

From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of the Modern Order

&lt;sc&gt;Mark Allen Eisner&lt;/sc&gt;. &lt;italic&gt;From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of the Modern Order&lt;/italic&gt;. University Park: Pennsylvania State University Press. 2000. Pp. 371. Cloth $65.00, paper $19.95

Journal Article Mark Allen Eisner. From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of the Modern Order. University Park: Pennsylvania State University Press. 2000. Pp. 371. Cloth $65.00, paper $19.95 Get access Eisner Mark Allen. From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of the Modern Order. University Park: Pennsylvania State University Press. 2000. Pp. 371. Cloth $65.00, paper $19.95. Edward D. Berkowitz Edward D. Berkowitz George Washington University Search for other works by this author on: Oxford Academic Google Scholar The American Historical Review, Volume 106, Issue 3, June 2001, Page 944, https://doi.org/10.1086/ahr/106.3.944 Published: 01 June 2001

From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of the Modern Order

From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of the Modern Order

Lineages of the Compensatory State - Marc Allen Eisner, From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of Modern Order (University Park: The Pennsylvania State University Press, 2000). Pp. x, 371. $19.95

Lineages of the Compensatory State - Marc Allen Eisner, From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of Modern Order (University Park: The Pennsylvania State University Press, 2000). Pp. x, 371. $19.95 - Volume 13 Issue 2

From warfare state to welfare state: World War I, compensatory state building, and the limits of the modern order

From warfare state to welfare state: World War I, compensatory state building, and the limits of the modern order

From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of the Modern Order. ByMarc Allen Eisner. University Park: Pennsylvania State University Press, 2000. 408 pp. Cloth, $65.00; paper, $19.95. ISBN: cloth 0-271-01995-6; paper 0-271-01996-4.

From Warfare State to Welfare State: World War I, Compensatory State Building, and the Limits of the Modern Order. ByMarc Allen Eisner. University Park: Pennsylvania State University Press, 2000. 408 pp. Cloth, 19.95. ISBN: cloth 0-271-01995-6; paper 0-271-01996-4. - Volume 74 Issue 4

Na+, K(+)-adenosine triphosphatase regulation in hypertrophied vascular smooth muscle cells.

Vascular smooth muscle cell hypertrophy is a normal compensatory state that may play a pathogenic role in hypertension. Angiotensin II stimulates a hypertrophic response in cultured vascular smooth muscle cells. As part of the growth response, angiotensin II rapidly activates the Na(+)-H+ exchanger, increasing Na+ influx. Because Na+, K(+)-ATPase is the major cellular mechanism for regulating intracellular Na+, we studied the effects of angiotensin II-induced hypertrophy on Na+, K(+)-ATPase expression and activity. Angiotensin II caused rapid increases in both steady-state Na+, K(+)-ATPase activity (ouabain-sensitive 86Rb uptake) and intracellular [Na+]. Angiotensin II also caused a sustained increase in Na+, K(+)-ATPase at 24 hours with a 73% increase in maximal 86Rb uptake per milligram protein and a fourfold increase in Na+, K(+)-ATPase alpha-1 messenger RNA levels. Thus, angiotensin II hypertrophy was associated with rapid increases in Na+, K(+)-ATPase activity due to increased Na+ entry and sustained increases due to a specific increase in Na+, K(+)-ATPase expression. These data demonstrate dynamic regulation of Na+, K(+)-ATPase at the functional and molecular level and suggest that similar compensatory mechanisms should be present in vivo. Alterations in such compensatory pathways may be fundamental to the pathogenesis of hypertension.