bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulatory Effects of Hyperprolactinemia on Aldosterone Secretion in Ovariectomized Rats
Authors: Kau Mei-Mei , Chang Ling-Ling , Kan Shu-Fen , Ho Low-Tone , Wang Paulus S. 
Published: August 2007

Background To evaluate the effects of hyperprolactinemia on aldosterone secretion and its mechanisms of action in ovariectomized (OVX) rats. Methods Hyperprolactinemia was induced by the transplantation of rat anterior pituitary (AP) glands under the kidney capsule for 6 weeks in female rats. Control rats underwent cerebral cortex (CX) transplantation. Four weeks after transplantation, the rats were OVX 2 weeks before decapitation. After decapitation, the trunk blood was collected, and the adrenal glands of CX- and AP-grafted rats were prepared as zona glomerulosa (ZG) cells for in vitro study. Results Plasma prolactin and aldosterone in the rats were increased by AP gland transplantation. In the in vitro study, the basal aldosterone secretion by the adrenal ZG cells was higher in AP-grafted rats than in CX-grafted rats. The AP-grafted group showed increased responsiveness to angiotensin II (10−8 M), KCl (8x10−3 M), or 8-bromo-adenosine 3′,5′-cyclic monophosphate (8-br-cAMP; 10−4 M, a membrane-permeable analogue of cAMP) with regard to aldosterone secretion as compared with the CX-grafted group. N-(2-[p-Bromocinnamylamine]ethyl)-5-isoquinolinesulfonamide (H89; 10−6, 10−5 M, a protein kinase A inhibitor) or tetrandrine (10−5 M, a blocker for both L-type and T-type Ca2+ channels) induced a greater suppression of aldosterone secretion in the AP-grafted group than in the CX-grafted group. No significant differences between the CX- and AP-grafted groups were observed, however, with regard to the adrenocorticotropic hormone (10−9 M)-, forskolin (10−5 M, an adenylyl cyclase activator)-, or nifedipine (10−5 M, an L-type Ca2+ channel blocker)-induced responsiveness of aldosterone secretion. In addition, there was no difference in the expression of desmolase (i.e., cytochrome P450 side-chain cleavage enzyme) in ZG cells between AP- and CX-grafted rats. The conversions of 25-OH-cholesterol into pregnenolone in the presence of trilostane (an inhibitor of 3β-hydroxysteroid dehydrogenase) and corticosterone into aldosterone, as well as the expression of the steroidogenic acute regulatory protein in ZG cells, were greater in AP-grafted rats than in CX-grafted rats. Conclusions These results suggest that hyperprolactinemia increases basal, angiotensin II- and KCl-stimulated aldosterone secretion by ZG cells in OVX rats through activation of T-type Ca2+ channels, the post-cAMP and protein kinase A pathway, cytochrome P450 side-chain cleavage enzyme, and aldosterone synthase, as well as by causing increased expression of steroidogenic acute regulatory protein in ZG cells.
Impaired Fibrinolysis in Premenopausal Women and Age-matched Men with Type 2 Diabetes Mellitus: A Pilot Study
Authors: Brandenburg Suzanne L. , Reusch Jane E.B. , Felder Kimberly K. , Nelson-Wong Erica , Lindenfeld JoAnn , Manco-Johnson Marilyn , Regensteiner Judith G. 
Published: August 2007

Background The presence of Type 2 diabetes mellitus (DM) is one of the strongest predictors of cardiovascular disease (CVD) in women. Although the specific mechanisms underlying this increased risk are unknown, one factor that may contribute to CVD in women with Type 2 DM is impaired fibrinolysis. Healthy premenopausal women have a low rate of CVD and excellent fibrinolytic potential. Impairment in fibrinolysis in people with DM has been demonstrated mainly in men, whereas the fibrinolytic potential of women with Type 2 DM has not been characterized well. This pilot study compared fibrinolytic measures in premenopausal women and men with DM with those of healthy age-matched control women and men to help determine whether fibrinolysis is abnormal in women with DM. Methods Fibrinolytic measurements included euglobulin clot lysis time (ELT), fibrinogen, plasminogen activator inhibitor 1, and tissue-type plasminogen activator. Results Poststasis ELT was significantly impaired in the women with DM as compared with the control women. The men with DM had a tendency toward slower poststasis ELT than did the control men, but the differences between the men's groups were not significant. In the women's groups only, we observed a trend toward increased plasminogen activator inhibitor 1 among the women with DM. Conclusions Women with DM have a more significant abnormality in poststasis ELT than do men with DM as compared with sex-specific counterparts without DM.
Pathogenic Mechanism, Prophylaxis, and Therapy of Symptomatic Acidosis Induced by Acetazolamide
Authors: Filippi Luca , Bagnoli Franco , Margollicci Maria , Zammarchi Enrico , Tronchin Michele , Rubaltelli Firmino F. 
Published: August 2007

Background Acetazolamide, a noncompetitive carbonic anhydrase inhibitor, can produce symptomatic acidosis and bone marrow suppression by a mechanism that is still unknown. This presentation occurs in the elderly, patients with renal or liver failure, people with diabetes, and newborns. The objective of this study was to understand the pathogenic mechanism of these adverse effects and to propose a possible prophylaxis and therapy. Methods Four human clinical cases were studied, and one animal experiment was performed. Four preterm newborns with posthemorrhagic ventricular dilation developed severe metabolic acidosis after treatment with acetazolamide. The acidosis suddenly disappeared after a packed red blood cell transfusion. Metabolic studies were performed in one patient and in newborn guinea pigs treated with 200 mg/kg acetazolamide. Results Acetazolamide can produce severe lactic acidosis with an increased lactate-to-pyruvate ratio, ketosis with a low β-hydroxybutyrate-to-acetoacetate ratio, and a urinary organic acid profile typical of pyruvate carboxylase deficiency. The acquired enzymatic injury resulting from the inhibition of mitochondrial carbonic anhydrase V that provides bicarbonate to pyruvate carboxylase can produce tricarboxylic acid cycle damage. We demonstrate that the dramatic disappearance of metabolic acidosis and normalizing metabolism after blood transfusion were due to the citrate contained in the packed red blood cell bag. This hypothesis was confirmed by animal experimentation. We argue that the metabolic disorder and bone marrow suppression may be related. Conclusion We demonstrate how acetazolamide can lead to symptomatic metabolic acidosis and probably to bone marrow suppression. We suggest citrate as a possible prophylaxis and treatment for these adverse reactions.
Safety Evaluation of Routine Intracoronary Acetylcholine Infusion in Patients Undergoing a First Diagnostic Coronary Angiogram
Authors: Tio R. A. , Monnink S. H. J. , Amoroso G. , Jessurun G. A. J. , Veeger N. , Volkers C. , Hautvast R. , Tan E. S. , Van Gilst W. H. , Van Boven A. J. 
Published: August 2007

Background Recent findings imply prognostic significance of intracoronary acetylcholine infusion for endothelial function testing. We evaluated whether routine use of this test in coronary angiography patients is safe. Methods Patients undergoing a first diagnostic coronary angiography were selected to receive intracoronary acetylcholine for endothelial function evaluation. The relation between adverse reactions during infusion and risk factors was analyzed with a logistic regression model. Included in the multiple logistic regression model were the variables with a univariate P value < 0.20. Results Adverse reactions occurred in 16% (49/299) of the patients. This included two life-threatening events caused by occlusive spasm and flow limitation in the left coronary artery. Other adverse events were chest pain (n = 38), AV block or sinus bradycardia (n = 10), dyspnea (n = 3). Adverse reactions were more likely to occur in patients younger than 60 years of age (relative risk, 5.6 [2.2–14.3]). Conclusion Intracoronary acetylcholine infusion is safe, but may lead to serious adverse reactions. Care should be taken especially in patients younger than 60 years of age. Routine use of acetylcholine infusion can thus only be justified if it has important prognostic significance. This has to be proven further in large prospective studies.
Isolation of Primary Rat Liver Fibroblasts
Authors: Kruglov Emma A. , Jain Dhanpat , Dranoff Jonathan A. 
Published: August 2007

Introduction One of the major advances in liver research in the past decade was the ability to isolate distinct liver cell populations. Although there are established methods of isolating hepatocytes, cholangiocytes, and stellate cells, before this study no technique for liver fibroblast isolation had been devised. Consequently, we developed a technique to isolate primary rat liver fibroblasts. Methods Fibroblasts were isolated from a freshly perfused rat liver with a modification of the procedure for isolation of rat cholangiocytes. Cell markers were assessed with the use of confocal immunofluorescence. Cell morphology was assessed with transmission electron microscopy. Expression of procollagen-1 was assessed by reverse transcription polymerase chain reaction. Results The appearance of cells with fibroblast morphology was first noted at 48 hours, and almost all cells in culture had fibroblast morphology at 96 hours. Putative fibroblasts stained for vimentin, but not for smooth muscle actin, von Willebrand factor, or cytokeratins. Cell morphology was consistent with that of fibroblasts and showed no features of epithelial, endothelial, or smooth muscle cells. Liver fibroblasts expressed procollagen-1 mRNA. Conclusion Primary isolated rat fibroblasts can be produced from a freshly perfused rat liver with a modification of standard cell culture methods. The role of fibroblasts in liver physiology can now be studied directly.
High Overexpression of the Human α-Galactosidase a Gene Driven by Its Promoter in Transgenic Mice: Implications for the Treatment of Fabry Disease
Authors: Ashley Grace A. , Desnick Robert J. , Gordon Ronald E. , Gordon Jon W. 
Published: August 2007

Background Human α-galactosidase A (α-Gal A) is the lysosomal enzyme that cleaves α-galactosyl residues from glycoconjugates and is the deficient enzyme in Fabry disease. To date, there have been no studies on the regulation of this “housekeeping” gene. Methods Transgenic mice were established with either 1) a 13.3-kilobase (kb) human genomic fragment that contained 246 bp of 5′- and approximately 2.8 kb of 3′- untranslated sequences, or 2) an “intronless” construct derived from the genomic sequence with the 5′ and 3′ flanking regions intact. Tissues that expressed high levels of α-Gal A activity were examined by light and electron microscopy. Results Transgenic mice were generated with 2 and 12 copies of the genomic sequence (Lines 1 and 2) or about 60 copies of the intronless construct (Lines 3 and 4). In mice hemizygous for the genomic transgene (Lines 1 and 2), tissue α-Gal A activities were 12 to 155 times higher than those in the respective wild-type tissue, depending on tissue and transgene copy number. Of note, the high overexpression did not alter the cellular or subcellular cytoarchitecture. In contrast, α-Gal A activities expressed by mice that carried the intronless construct were only two- to sixfold more than in wild-type tissues in which the genomic transgene was highly expressed. Conclusions The remarkably high levels of α-Gal A expression in transgenic mice carrying the intact genomic sequence versus the intronless construct suggested that the genomic sequence contained a strong intronic enhancer element. Identification of this regulatory element or elements may be useful in efforts to overexpress human α-Gal A for gene therapy endeavors. In addition, overexpression of human α-Gal A did not affect cellular morphology, which indicates that its overexpression in gene therapy endeavors should be safe.
Disruption of Mitochondrial Calcium Homeostasis after Chronic α-Naphthylisothiocyanate Administration: Relevance for Cholestasis
Authors: Rolo Anabela P. , Oliveira Paulo J. , Seiça Raquel , Santos Maria S. , Moreno António J. , Palmeira Carlos M. 
Published: August 2007

Background Hepatocyte dysfunction caused by impaired mitochondrial function has been pointed out as a probable leading cause of cholestatic liver injury. The aim of this study was to evaluate liver mitochondrial bioenergetics that followed repeated in vivo administration of α-naphthylisothiocyanate, a known cholestatic agent. Methods Serum markers of liver injury and endogenous adenine nucleotides were measured in α-naphthylisothiocyanate-treated rats (intraperitoneally, 100 mg/Kg/wkx6 wk). Changes in membrane potential, mitochondrial respiration, as well as alterations in mitochondrial calcium homeostasis were monitored. Results In rats injected with α-naphthylisothiocyanate, liver injury with cholestasis developed within 48 hours, as indicated by both serum enzyme activities and total bilirubin concentration. However, 1 week after the last injection, serum enzyme activity returned to control levels. In addition, after chronic α-naphthylisothiocyanate administration, no alterations in mitochondrial respiratory function and membrane potential were observed. Associated with these parameters, mitochondria from treated animals exhibited increased susceptibility to disruption of mitochondrial calcium homeostasis by calcium phosphate and by bile acids, which was probably caused by induction of permeability transition pore. Conclusions Our data suggest that chronic cholestasis in rats leads to impaired mitochondrial function due to the disruption of mitochondrial calcium homeostasis. The initiating event is the induction of a cyclosporine A-sensitive release of calcium. This event may be an important determinant of the progression of cholestatic liver injury and associated liver cirrhosis. In addition, in the present study we observed that impairment of mitochondrial function is potentiated by chenodeoxycholate, a bile acid that is known to be toxic. Ursodeoxycholate (the β- epimer of chenodeoxycholate) is approved for the treatment of chronic cholestatic liver disease. Interestingly, we show that the susceptibility to the cyclosporine A-sensitive release of calcium was increased by the combination of both bile acids. These results indicate that the reported improvement of biochemical parameters in cholestatic patients treated with ursodeoxycholate would not prevent the associated mitochondrial dysfunction. This may explain the progression of the histological stage and the maintenance of symptoms during cholestasis.
Various Clinical Manifestations in Patients with Thrombotic Microangiopathy
Authors: Chang Jae C , Kathula Satheesh K 
Published: August 2007

Background Thrombotic microangiopathy (TM) is characterized by thrombocytopenia and microangiopathic hemolytic anemia in association with diffuse microthrombi in the arteriolar capillaries of various organs. Its clinical manifestation is protean, and a few well-defined clinical syndromes have been recognized. A clear understanding of the consequence of TM is needed to appreciate the unusual clinical syndromes due to atypical presentation of thrombotic thrombocytopenic purpura (TTP). Methods The medical records of patients with known diagnoses of TTP, hemolytic uremic syndrome (HUS), and the syndrome in which hemolysis, elevated liver enzymes, and low platelet count are found in association with pregnancy were examined retrospectively from 1981 to 1994 and prospectively from 1995 to 2000. Various thrombotic microangiopathic presentations were identified in these patients. Their response to exchange plasmapheresis was evaluated, and their clinical outcome was determined. Results A total of 74 patients were diagnosed with TM. Among these patients, several well-defined thrombotic microangiopathic presentations were identified. These presentations included TTP in 57 patients, acute respiratory distress syndrome (ARDS) in 13 patients, HUS in 9 patients, the syndrome in which hemolysis, elevated liver enzymes, and low platelet count are found in association with pregnancy in 9 patients, peripheral digit ischemic syndrome (PDIS) in 6 patients, pancreatitis in 3 patients, hepatitis in 3 patients, and nonocclusive mesenteric ischemia (NOMI) in 2 patients. Exchange plasmapheresis was an effective treatment, with a response rate of 79%. A poor prognosis was evident when ARDS was present, with an overall survival rate of 46%. Conclusion Traditionally, TTP and HUS are considered the main entities of TM. It is evident that other manifestations of TM, if unrecognized in a timely fashion, can lead to fatality. The understanding of the pathophysiologic consequences of TM and the recognition of its atypical presentations are essential to achieve favorable outcomes in patients with this life-threatening disease.
Endothelial Dysfunction in Patients with Coronary Artery Disease: A Comparison of Three Frequently Reported Tests
Authors: Monnink Stefan H. J. , Van Haelst Paul L. , Van Boven Ad J. , Stroes Erik S. G. , Tio René A. , Plokker Thijs W. M. , Smit Andries J. , Veeger Nic J. G. M. , Crijns Harry J. G. M. , Van Gilst Wiek H. 
Published: August 2007

Background Endothelial dysfunction is useful in predicting future cardiovascular disease. At present several tests are available to test endothelial function: coronary diameter response to acetylcholine, forearm bloodflow (FBF) response to acetylcholine, and brachial artery flow-mediated dilative (FMD) response to postischemic hyperemia. This study aimed to compare the three most frequently reported endothelial function tests. Methods Twenty-eight patients (19 males and nine females, mean age 57 years) referred for diagnostic coronary angiography were considered for endothelial function measurement in the coronary artery as well as in the forearm by FBF and FMD. Results Acetylcholine decreased the mean coronary diameter by 7.4% (SD 6.3%) and increased the mean FBF by 230% (SD 152%). Hyperemia increased the mean brachial diameter by 6.7% (SD 4.8%). The effect of acetylcholine on forearm resistance vessels was significantly related to the effect of acetylcholine on the coronary conduit vessels ( P=0.039). Nonetheless, FMD was not related to FBF nor to the coronary response. Conclusion In patients with mild coronary endothelial dysfunction, forearm vasoreactivity is related to the coronary response, provided that the same stimulus is used.
Effects of Enhanced External Counterpulsation on Health-Related Quality of Life Continue 12 Months after Treatment: A Substudy of the Multicenter Study of Enhanced External Counterpulsation
Authors: Arora Rohit R. , Chou Tony M. , Jain Diwakar , Fleishman Bruce , Crawford Lawrence , McKiernan Thomas , Nesto Richard , Ferrans Carol Estwing , Keller Susan 
Published: August 2007

Background The Multicenter Study of Enhanced External Counterpulsation (MUST-EECP) was the first prospective, randomized, blinded, sham-controlled study of enhanced external counterpulsation (EECP) in the treatment of chronic stable angina. We previously reported that EECP therapy lengthens the time to exercise-induced myocardial ischemia and reduces angina. We now describe the effects of EECP therapy versus a sham-treated control group in terms of patients’ functioning, their senses of well-being and other Health-Related Quality Of Life (HQOL) parameters from baseline to end of treatment and from baseline to 12 months after treatment. Objective To determine whether a 35-hour course of EECP affects the HQOL of patients with symptomatic coronary artery disease, 12 months following treatment. Methods Seventy-one of the 139 patients enrolled in MUST-EECP provided evaluable patient-completed questionnaires at baseline, at the end of treatment, and 12 months post-treatment. The Medical Outcomes Study 36-Item Short-Form Health Survey and the Quality of Life Index-Cardiac Version III were used to assess effects on HQOL. Results Both groups had similar HQOL scores at baseline. At end of treatment and at 12-month follow up, patients who had active-CP reported greater improvement than those who had inactive-CP in all nine quality of life scales, including ability to perform activities of daily living, ability to work, bodily pain, confidence in health, energy, ability to engage in social activities with family and friends, anxiety and depression, and quality of life issues from the effects of angina on health and functioning. Despite small sample sizes, active-CP patients demonstrated significantly greater improvement at 12 months following treatment in bodily pain, social functioning, and quality of life specific to cardiac patients compared with inactive-CP patients. Conclusion Significant health-related quality of life improvements were measurable up to 12 months after the completion of treatment with EECP. Improvements in this controlled study are consistent with HQOL changes reported in case series and patient registries. Larger studies are warranted.
External Bioenergy Increases Intracellular Free Calcium Concentration and Reduces Cellular Response to Heat Stress
Authors: Kiang Juliann G. , Marotta Diane , Wirkus Mietek , Wirkus Margaret , Jonas Wayne B. 
Published: August 2007

Background External bioenergy (energy emitted from the body) can influence a variety of biological activities. It has been shown to enhance immunity, promote normal cell proliferation, increase tumor cell death, and accelerate bone fracture recovery. In this study, we investigated whether external bioenergy could alter intracellular calcium concentration ([Ca2+]i, an important factor in signal transduction) and regulate the cellular response to heat stress in cultured human lymphoid Jurkat T cells. Methods A practitioner emitted bioenergy toward tubes of cultured Jurkat cells for one 15-minute period. [Ca2+]i was measured spectrofluorometrically using the fluorescent probe indo-1. The heat shock protein 72 kd was detected using35 S-methionine prepulse and Western blot analysis. Results The resting [Ca2+]i in Jurkat T cells was 90±3 nM in the presence of external calcium. The removal of external calcium decreased the resting [Ca2+]i to 54±2 nM, indicating that Ca2+ entry from the external source is important for maintaining the basal level of [Ca2+]i. In the presence of external Ca2+, treatment of Jurkat T cells with external bioenergy for 15 minutes increased [Ca2+]i by 22±3%. [Ca2+]i remained elevated in these cells for 2 hours. Surprisingly, we also observed that [Ca2+]i increased by 11±1% if cells were simply placed in the area where external bioenergy had been used. This lingering effect of external bioenergy dissipated within 24 hours. Treatment with external bioenergy reduced cellular responses to heat stress and did not induce the production of heat shock protein 72 kd, which is known to provide cytoprotection. Conclusions These results suggest that externally applied bioenergy can upregulate [Ca2+]i and downregulate the cellular response to stress. The association between the external bioenergy and increases in [Ca2+]i may be a good index for detecting presence of bioenergy.