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At least 235 records · Page 13Linked to original sources
PubMed2003

Role of the paraventricular nucleus in renal excretory responses to acute volume expansion: role of nitric oxide.

Acute volume expansion (VE) produces a suppression of renal sympathetic nerve discharge (RSND) resulting in diuresis and natriuresis. Recently, we have demonstrated that the endogenous nitric oxide (NO) system within the paraventricular nucleus (PVN) produces a decrease in RSND. We hypothesized that endogenous NO in the PVN is involved in the suppression of RSND leading to diuretic and natriuretic responses to acute VE. To test this hypothesis, we first measured the VE-induced increase in renal sodium excretion and urine flow with and without blockade of NO, with microinjection of NG-monomethyl-L-arginine (L-NMMA; 200 pmol in 200 nl), within the PVN of Inactin-anesthetized male Sprague-Dawley rats. Acute VE produced significant increases in urine flow and sodium excretion, which were diminished in rats treated with L-NMMA within the PVN. This effect of NO blockade within the PVN on VE-induced diuresis and natriuresis was abolished by renal denervation. Consistent with these data, acute VE induced a decrease in RSND (52% of the baseline level), which was significantly blunted by prior administration of L-NMMA into the PVN (28% of the baseline level) induced by a comparable level of acute VE. Using the push-pull perfusion technique, we found that acute VE induced a significant increase in NOx concentration in the perfusate from the PVN region. Taken together, these results suggest that acute VE induces an increase in NO production within the PVN that leads to renal sympathoinhibition, resulting in diuresis and natriuresis. We conclude that NO within the PVN plays an important role in regulation of sodium and water excretions in the volume reflex via modulating renal sympathetic outflow.

Animals↗
PubMed2004

The role of bisphosphonates in the management of advanced cancer with a focus on non-small-cell lung cancer. Part 1: Mechanisms of action, role of biomarkers and preclinical applications.

With recent advances in cancer management, patients with metastatic bone disease are likely to have a prolonged clinical course, with skeletal-related events such as pain, hypercalcemia, pathologic fractures, spinal cord and nerve compression. Bisphosphonate use has resulted in the reduction of skeletal-related complications for a number of tumors including breast, prostate and myeloma, and improvements in the quality of life for patients. There is now evidence that newer, highly potent, nitrogen-containing bisphosphonates reduce skeletal complications in patients with bone metastases from other solid tumors (including lung cancer). The early identification of patients at high risk for developing bone metastases may help curtail a complex and costly clinical problem--skeletal-related events. In this article, we review the different mechanisms of bisphosphonates and the potential role of newer-generation bisphosphonates, such as zoledronic acid, in the management of advanced, metastatic bone disease. We include a review of mechanistic studies and preclinical data. Additionally, the utility of evolving concepts such as bone markers and imaging of bone metastases are discussed.

Antineoplastic Agents↗
PubMed1980

The complementary roles of M-mode echocardiography and scintigraphy in the evaluation of adults with suspected left-to-right shunts. Additional observations on the role of two-dimensional echocardiography.

We sought to determine the relative clinical abilities and roles of echocardiography and scintigraphy in left-to-right shunt diagnosis. M-mode echocardiographic and scintigraphic studies were analyzed in 37 adults presenting diagnostic difficulties with suspected left-to-right shunts. The historic, physical, radiographic and electrocardiographic data were frequently ambiguous. An enlarged right ventricle on M-mode echocardiography was a sensitive (100%) but not specific (55%) indicator of atrial septal defect (ASD). M-mode lacked sensitivity for ventricular septal defect (VSD) and patent ductus arteriosus (PDA). In a few studies, two-dimensional echocardiography provided additional specific and clinically important anatomic information. Scintigraphic analysis demonstrated complete diagnostic accuracy and excellent localizing and quantitative abilities in all patients studied. Because it is extremely sensitive to ASD, free of any exposure to radioactivity, entirely noninvasive and may be simply and visually analyzed, echocardiography is the study of choice in the preliminary evaluation of patients presenting diagnostic difficulty with suspected ASD. Scintigraphy is the study of choice in the preliminary evaluation of patients presenting diagnostic difficulty with suspected VSD and PDA and is the logical response to the finding of echocardiographic right ventricular enlargement when the diagnosis remains in doubt.

Cardiac Catheterization↗
PubMed2000

Exhaled nitric oxide in high-altitude pulmonary edema: role in the regulation of pulmonary vascular tone and evidence for a role against inflammation.

High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed subjects at altitudes above 2,500 m. It is not clear whether, in addition to hemodynamic factors and defective alveolar fluid clearance, inflammation plays a pathogenic role in HAPE. We therefore made serial measurements of exhaled pulmonary nitric oxide (NO), a marker of airway inflammation, in 28 HAPE-prone and 24 control subjects during high-altitude exposure (4,559 m). To examine the relationship between pulmonary NO synthesis and pulmonary vascular tone, we also measured systolic pulmonary artery pressure (Ppa). In the 13 subjects who developed HAPE, exhaled NO did not show any tendency to increase during the development of lung edema. Throughout the entire sojourn at high altitude, pulmonary exhaled NO was roughly 30% lower in HAPE-prone than in control subjects, and there existed an inverse relationship between Ppa and exhaled NO (r = -0.51, p < 0.001). These findings suggest that HAPE is not preceded by airway inflammation. Reduced exhaled NO may be related to altered pulmonary NO synthesis and/or transport and clearance, and the data in our study could be consistent with the novel concept that in HAPE-prone subjects, a defect in pulmonary epithelial NO synthesis may contribute to exaggerated hypoxic pulmonary vasoconstriction and in turn to pulmonary edema.

Adult↗
PubMed2002

Essential role for the BH3-only protein Bim but redundant roles for Bax, Bcl-2, and Bcl-w in the control of granulocyte survival.

Programmed cell death of granulocytes is one of the mechanisms that limit inflammatory responses. Members of the Bcl-2 protein family are essential regulators of apoptosis induced by growth factor withdrawal or cytotoxic stress. We have used gene-targeted and transgenic mice to investigate the roles of the prosurvival molecules Bcl-2 and Bcl-w and their proapoptotic relatives Bax and Bim in spontaneous and stress-induced apoptosis of granulocytes from bone marrow or the peritoneum. Bim deficiency, like Bcl-2 overexpression, rendered granulocytes resistant to cytokine withdrawal and cytotoxic drugs, but absence of Bax alone had no protective effect. Loss of Bcl-2 or Bcl-w did not increase the sensitivity of granulocytes to any of these apoptotic stimuli, but Bcl-2 was essential for the in vitro survival of myeloid progenitors under conditions of cytokine withdrawal where cell death was mediated, in part, by Bim. Granulocyte colony-stimulating factor (G-CSF), a key survival factor for granulocytes, enhanced viability of cells lacking bcl-2, bcl-w, bax, or bim, indicating that none of these genes alone is the essential target of this cytokine's prosurvival function. Expression analysis of proapoptotic Bcl-2 family members in granulocytes revealed that the BH3-only protein Bmf is induced upon cytokine withdrawal. These results indicate that the BH3-only protein Bim and possibly also Bmf are critical initiators of spontaneous and drug-induced apoptosis of granulocytes, whereas Bcl-2, Bcl-w, and Bax act in a redundant manner in regulating granulocyte survival and death, respectively.

Animals↗
PubMed2004

Distinct roles for IP-10/CXCL10 in three animal models, Theiler's virus infection, EAE, and MHV infection, for multiple sclerosis: implication of differing roles for IP-10.

Theiler's murine encephalomyelitis virus (TMEV) causes demyelination with inflammation of the central nervous system (CNS) in mice and is used as an animal model for multiple sclerosis (MS). Interferon-gamma inducible protein-10 kDa (IP-10) is a CXC chemokine and a chemoattractant for CXCR3+ T cells. IP-10 mRNA is expressed in the CNS during TMEV infection. However, administration of anti-IP-10 serum caused no difference in clinical signs, inflammation, demyelination, virus persistence or anti-virus antibody response in TMEV infection, while levels of virus specific and autoreactive lymphoproliferation increased. This likely reflects a difference in the pathogenesis of TMEV infection from that of two other animal models for MS, mouse hepatitis virus infection and experimental allergic encephalomyelitis (EAE), where blocking of IP-10 resulted in clinical and histological improvement with suppression of antigen specific lymphoproliferation. In this review, we compare and contrast the roles of IP-10 between the three animal models for MS, and discuss the relevance to MS patients with different clinical courses.

Animals↗
PubMed1983

Control of corpus luteum function in the pregnant rabbit: role of estrogen and lack of a direct luteotropic role of the placenta.

The corpus luteum is essential for pregnancy maintenance in the rabbit and appears to require two luteotropins: estrogen from ovarian follicles and a placental luteotropic factor. We have investigated the role of the placental luteotropic factor in maintaining corpus luteum function in the pregnant rabbit in the absence of estrogen. In Exp 1, follicular estrogen was withdrawn on day 21 of pregnancy by ovulating follicles with 10 IU hCG. In Exp 2, estrogen was withdrawn in hypophysectomized pregnant rabbits on day 21 by removing an estradiol (E2) implant. In the presence of this estrogen implant, luteal function and pregnancy are maintained after hypophysectomy, performed on day 4 of pregnancy. In both experiments, fetoplacental viability was ensured by treating the rabbits with medroxyprogesterone acetate (MPA). In both Exp 1 and 2, withdrawal of estrogen on day 21 of pregnancy caused a dramatic decline in serum progesterone concentrations by day 22. Serum progesterone concentrations remained low, and corpora lutea regressed, although viable fetuses were maintained with MPA. In animals not receiving MPA, estrogen withdrawal caused the loss of luteal function, followed by abortion on days 23-24. In contrast, estrogen replacement (via E2 implant) on day 22 in Exp 1 was fully capable of restoring serum progesterone concentrations to pretreatment values on days 24-27 in MPA-treated rabbits. In rabbits not receiving MPA, estrogen replacement also restored serum progesterone concentrations and prevented abortion. These results provide further evidence that estrogen is essential for normal luteal function in the pregnant rabbit. In the absence of estrogen, the rabbit placenta maintained by the progestagen MPA has no direct luteotropic activity.

Animals↗
PubMed2003

Role of cyclical pressure and particles in the release of M-CSF, chemokines, and PGE2 and their role in loosening of implants.

A septic loosening of orthopaedic implants is usually attributed to the action of wear debris from the prosthesis. Recent studies, however, have also implicated physical pressures in the joint as a further cause of loosening. We have examined the role of both wear debris and pressure on the secretion of two chemokines, MIP-1alpha and MCP-1, together with M-CSF and PGE2, by human macrophages in vitro. The results show that pressure alone stimulated the secretion of more M-CSF and PGE2 when compared with control cultures. Particles alone stimulated the secretion of M-CSF and PGE2, when compared with unstimulated control cultures, but did not stimulate the secretion of the two chemokines. Exposure of macrophages to both stimuli simultaneously had no synergistic effect on the secretion of the chemokines, but both M-CSF and PGE2 were increased in a synergistic manner. Our findings suggest that pressure may be an initiating factor for the recruitment of cells into the periprosthetic tissue.

Chemokine CCL2↗
PubMed1999

[The role of discharge coordination nurses in a university hospital--changes in the role with timing of the discharge request].

UNLABELLED: We studied the role of discharge assisting nurses who coordinate discharge planning (DP). The requests for DP were ordered at different periods during the admission. The periods were mainly divided into three phases in which the DP was ordered from the wards, which were type 1: just before discharge, type 2: after the decision to discharge, and type 3: between admission and the decision to discharge. We analyzed 8 cases, DP ordered in the type 3 phase provided the most satisfactory outcome for patients' home lives, since the nurse, other medical staff and patients had sufficient time to prepare and provide the needed services. CONCLUSION: It was clarified that type 3 provided the best outcome of discharge planning.

Hospitals, University↗
PubMed2000

[The role of sulphonylurea derivatives in treatment of diabetes type 2. The role of glimepiride].

Type 2 diabetes is characterised by some kind of duality. In its pathogenesis an important role have as well genetic as environmental factors. Both of them influence the insulin secretion at the one side and the insulin resistance at the other one. Very important group of antidiabetic drugs are sulphonylureas. They bind to the sulphonylurea receptor localized at the potassium channel in the cellular membrane. Contemporary sulphonylurea derivatives should be characterised by rather weak binding with the receptor, action during mealtime only (prandial regulation of glycemia), not to strong insulin secretion and for the quality of life reason once daily application. This criteria are fulfilled by e.g. slow-releasing preparations of glipizide and glikiazide and also by glimepiride.

ATP-Binding Cassette Transporters↗
PubMed1992

[Role of neuropeptides in the pathogenesis of pain syndrome in autonomic and sensory polyneuropathy of occupational etiology and their role in the therapeutic action of laser acupuncture].

Biochemical studies of opiate system in patients with occupational diseases showed the role of the central pain regulating system inducing the pain syndrome in autonomic and sensory polyneuropathy caused by occupational factors. Increased production of the pain-reducing endogenic neuropeptides such as endorphin and leucine enkephalin was found one of the He-Ne laser acting principles which restore the pain adaptation in human. A repeated course of laser therapy would normalize the content of both neuropeptides. Blood levels of neuropeptides may serve for evaluating the pain syndrome and estimating of laser therapy effects.

Acupuncture Therapy↗
PubMed2004

Testosterone levels and stress in women: the role of stress coping strategies, anxiety and sex role identification.

This study evaluated the relation between testosterone changes in response to anticipatory stress and several psychological variables that contribute to the stress reaction. Salivary testosterone was determined in 76 female students under stress-free conditions and before an important examination. Individual stress reactions were highly variable in direction and extent: both significant increases and decreases were found. Thus the data did not confirm previous findings of general increases in testosterone levels under stress in women. Depending on the women's level of trait anxiety (assessed via STAI) and the general use of positive or negative cognitive coping strategies (assessed via SVF), we found significant differences in their baseline testosterone levels. Individual endocrine changes under stress were correlated with baseline testosterone levels: High testosterone concentrations at rest were more likely to drop under anticipatory stress than low concentrations. These contrasting effects can be explained by the significant interaction of trait anxiety and the sex role dimension of masculinity (assessed via BSRI) with testosterone production in females.

Adaptation, Psychological↗
PubMed2004

[The role of platelet-derived growth factor A (PDGF-A) in hypertension and renal diseases. Part 1: Structure and regulation of the PDGF-A gene expression and its role in hypertension].

Platelet-derived growth factor is commonly known as a mitogen. There are four members of PDGF family known as PDGF-A chain, PDGF-B chain, PDGF-C chain and PDGF-D chain, which in active forms are dimers. As far as two receptors PDGF-alphaR and PDGF-betaR are known to bind PDGF There is a difference in binding affinity of various forms of PDGF by those receptors. Two different transcripts are derived from PDGF-A gene by alternative splicing. Transcription of PDGF-A gene is under control of many factors. Many research data suggest a role for PDGF-A in smooth muscle cell hyperplasia in hypertension and atherosclerosis. Since inhibition of PDGF-A transcription by a specific ribozyme represses smooth muscle cell proliferation in arteries, introduction of gene therapy might be of value in the treatment of hypertension and its complications.

Humans↗
PubMed2004

[Prevalence of patellofemoral pain syndrome. Evaluation of the role of biomechanical malalignments and the role of sport activity].

INTRODUCTION: Disorders around the patella are the most frequent knee complaints seen in adolescents. In the literature many intrinsic and extrinsic risk factors have been linked to Patellofemoral Pain Syndrome (PFPS), but the role of these risk factors is controversial. AIM: The goal of this study was to evaluate the prevalence of PFPS in a group of adolescents aged 12-20 years in Hungary, and to gain more information on the relationship between the biomechanical anomalies of the lower extremity and the PFPS. MATERIAL AND METHODS: In this epidemiological study the authors investigated the effect of sporting activity in the maturation of symptoms among 586 randomly selected students. Different physical examinations, anthropometric measurements, stability tests, footscan analysis were performed. RESULTS: Concerning the prevalence of this syndrome they could not find any differences between males (n = 60, 20.41%) and females (n = 61, 20.89%). The authors could not identify any statistically significant intrinsic risk factors, although changes in the Q angle may be linked to increased prevalence of PFPS. The study supports the theory of the importance of "overload", for there was a significant correlation between the prevalence of PFPS and the different levels of sporting activities (competitive, recreational and non-athletes). CONCLUSION: The authors concluded that the prevalence of PFPS among Hungarian students is 20.65%.

Adolescent↗
PubMed1990

Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. I. Stimulatory role of a variety of mesenchymal cell activators and inhibitory role of TGF-beta.

Long-term marrow cultures (LTMC) allow the proliferation and differentiation of primitive human hematopoietic progenitor cells to be maintained for many weeks in the absence of exogenously provided hematopoietic growth factors. Previous investigations focused on defining various types of cells that are present in this culture system and on measuring the cycling behavior of the different subpopulations of colony-forming cells maintained within it. These studies suggested that mesenchymal stromal elements derived from the input marrow play a key role in regulating the turnover of the most primitive, high-proliferative potential erythroid and granulopoietic colony-forming cells that are found almost exclusively in the adherent layer of LTMC. In this study we show that the re-entry into S-phase of these primitive hematopoietic progenitors that occurs after each weekly medium change is due to an as yet undefined constituent of horse serum, which is absent from fetal calf serum. However, this effect is not unique to the factor present in horse serum. It is also elicited by the addition to LTMC of several well-defined growth regulatory molecules, ie, platelet-derived growth factor (PDGF), interleukin-1 (IL-1), transforming growth factor alpha (TGF-alpha), and IL-2. None of these was able to stimulate hematopoietic colony-forming cells in methylcellulose assays, although all have known actions on mesenchymal cells including, in some cases, the ability to increase production of growth factors that can stimulate primitive high-proliferative potential hematopoietic progenitors in clonogenic assays. Interestingly, a stimulating effect was not obtained after addition of endotoxin to LTMC. TGF-beta, a direct-acting negative regulator that acts selectively on primitive hematopoietic progenitor cells if added to LTMC simultaneously with new medium or IL-1, blocked their stimulating activity. These results suggest a model in which indirect, local modulation of both positive and negative regulatory factors via effects on mesenchymal elements determines the rate of turnover of adjacent populations of very primitive hematopoietic cells that are normally maintained in a quiescent state in vivo.

Bone Marrow Cells↗
PubMed1984

The alimentary canal, liver and vagus play a role in short-term feeding: but is the role regulation, correlation, glucostasis or spurious association?

The injection of insulin has been used to produce increased food intake and, when given over a period of time, to produce obesity. The hormone, however, is released in 3 distinct phases when subjects encounter and ingest food and one would expect that insulin release would be a correlate, if not a contributory factor, to satiety. On the other hand, glucagon has been used to suppress food intake, but pancreatic glucagon should be released during the absence of food. The present paper investigates the physiologic function of these hormones and gives evidence that insulin serves as part of the normal sequence of hormonal and neural responses to food intake and does appear to play a contributory, causal role in short-term satiety for food intake.

Animals↗
PubMed1978

Role of interferon in the pathogenesis of viral diseases of mice as demonstrated by the use of anti-interferon serum. V. Protective role in mouse hepatitis virus type 3 infection of susceptible and resistant strains of mice.

Potent sheep anti-mouse interferon globulin has been used to determine the role of virus-induced interferon in mouse hepatitis virus type 3-infected susceptible (C57BL/6), semiresistant (C3H/He), and resistant (A/J) strains of mice. Injection of anti-interferon globulin accelerated the onset of death in C57BL/6 mice, induced almost 100% mortality in C3H/He mice that usually do not die of acute disease, and caused death in 4- and 6-week-old A/J mice, but not in older mice. We conclude that interferon is an important host defense factor in the initial response of different strains of mice to MHV-3 infection. Other factors, however, such as the capacity of macrophages to restrict viral multiplication probably underlie the genetically determined susceptibility or resistance of mice to MHV-3 infection.

Animals↗