The renal community is faced with an ever increasing number of patients reaching end-stage renal ... more The renal community is faced with an ever increasing number of patients reaching end-stage renal failure. Clinical studies have provided clear evidence that angiotensin-converting enzyme (ACE) inhibitors, and probably also AT1 receptor antagonists, at least in patients suffering from type 2 diabetes, slow disease progression to end-stage renal failure. This protective effect of drugs interfering with the renin-angiotensin system (RAS) are in part independent of reduction in systemic blood pressure, but involve normalization of glomerular hyperperfusion and hyperfiltration, restoration of altered glomerular barrier function, and reduction of stimulated tubular fluid reabsorption. Angiotensin II (ANG II) has emerged in the last decade as a multifunctional cytokine exhibiting many non-hemodynamic properties such as acting as a growth factor and profibrogenic cytokine, and even having proinflammatory properties. This review tries to bridge the classical hemodynamic actions of ANG II in the kidney with the more recently characterized effects of this vasopeptide. Finally, clinical implications are suggested based on data from clinical studies. A thorough understanding of the RAS is important to recognize the potential of nephroprotective strategies through inhibition of its components.
To investigate the relationship between ionized calcium and disease activity, parameters of bone ... more To investigate the relationship between ionized calcium and disease activity, parameters of bone metabolism and bone mineral density (BMD) at the lumbar spine (BMD-LS) and the femoral neck (BMD-FN) measured by dual X-ray absorptiometry in rheumatoid arthritis (RA). In 146 patients with RA, the following parameters were investigated: serum levels of ionized calcium, total calcium, vitamin D metabolites 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3), intact parathyroid hormone (iPTH), interleukin-6, osteocalcin, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP); renal excretion of pyridinolin (PYD)- and desoxypyridinolin (DPD)-crosslinks. A total of 30.1% of the patients were hypercalcemic (ionized calcium >1.30 mmol/l). In comparison with normocalcemic patients, those with hypercalcemia had significantly higher ESR (P<0.01) and CRP values (P<0.05) and significantly lower serum levels of both iPTH (P<0.01) and 1,25D3 (P<0.05) and a significantly lower BMD-LS (P<0.05). The results indicate that a substantial part of RA patients is hypercalcemic. Hypercalcemia is associated with high disease activity and may contribute to suppression of PTH secretion and vitamin D hormone synthesis. High levels of ionized calcium may be a reflection of disease-activity-related systemic bone loss, and could be a predictor of BMD at the lumbar spine in RA.
Naunyn-Schmiedeberg's Archives of Pharmacology, 1998
Two types of receptors for gastrin and cholecystokinin (CCK) have been identified in the gastroin... more Two types of receptors for gastrin and cholecystokinin (CCK) have been identified in the gastrointestinal tract and in the central nervous system: CCK(A) and CCK(B) receptors. Here we report evidence for the expression of CCK(B) receptors in the guinea-pig kidney. Specific binding sites for [125I]gastrin were detected in sections of the guinea-pig kidney: Binding was saturable, pH-, temperature- and time-dependent, and specific for gastrin-related peptides. The potencies for inhibition of binding of [125I]gastrin were CCK-8 > gastrin 17-I > CCK(B) receptor antagonist L-365,260 > des(SO3)CCK-8 > CCK(A) receptor antagonist L-364,718. Autoradiography demonstrated specific [125I]gastrin binding to medullary collecting ducts and to a much lesser extent to glomeruli, but not over other structures. CCK(B) receptor cDNA fragments were amplified by RT-PCR from total kidney, isolated tubuli and from tissues known to express CCK(B) receptors such as stomach and brain. The kidney might therefore be a previously unidentified site of action for gastrin and cholecystokinin-related peptides.
The aim of the study was to compare transthoracic sonography (TS) with multislice computed tomogr... more The aim of the study was to compare transthoracic sonography (TS) with multislice computed tomography (MSCT) in the detection of peripheral pulmonary embolism (PE). In addition, the study verified peripheral parenchymal findings visualized by TS and MSCT. A total of 33 patients (16 females, 17 males; mean age = 65.4 years) with symptoms of suspected PE were enrolled in the study. TS and MSCT were undertaken within 24 h of the beginning of clinical PE signs. Ten patients suffered from PE as visualized by MSCT. The sensitivity of TS for detecting PE was 70.0% and the specificity was 69.6%. Preferentially, PE and peripheral parenchymal findings were situated in the lower lobes. Oligemia was the main parenchymal alteration detected by MSCT. TS demonstrated that wedge-shaped consolidations were frequently associated with PE. In addition, localized pleural effusion was a typical finding in the presence of PE for both TS and MSCT. TS had moderate sensitivity and specificity compared with MSCT. Furthermore, the study revealed that PE is often associated with peripheral parenchymal changes, both of which are detectable by TS and MSCT. In case of contraindication with MSCT, TS is a potential technique for diagnosing PE-related parenchymal findings and can serve as an alternative method in the diagnosis of PE. However, a negative result with TS does not rule out a PE.
The renal community is faced with an ever increasing number of patients reaching end-stage renal ... more The renal community is faced with an ever increasing number of patients reaching end-stage renal failure. Clinical studies have provided clear evidence that angiotensin-converting enzyme (ACE) inhibitors, and probably also AT1 receptor antagonists, at least in patients suffering from type 2 diabetes, slow disease progression to end-stage renal failure. This protective effect of drugs interfering with the renin-angiotensin system (RAS) are in part independent of reduction in systemic blood pressure, but involve normalization of glomerular hyperperfusion and hyperfiltration, restoration of altered glomerular barrier function, and reduction of stimulated tubular fluid reabsorption. Angiotensin II (ANG II) has emerged in the last decade as a multifunctional cytokine exhibiting many non-hemodynamic properties such as acting as a growth factor and profibrogenic cytokine, and even having proinflammatory properties. This review tries to bridge the classical hemodynamic actions of ANG II in the kidney with the more recently characterized effects of this vasopeptide. Finally, clinical implications are suggested based on data from clinical studies. A thorough understanding of the RAS is important to recognize the potential of nephroprotective strategies through inhibition of its components.
To investigate the relationship between ionized calcium and disease activity, parameters of bone ... more To investigate the relationship between ionized calcium and disease activity, parameters of bone metabolism and bone mineral density (BMD) at the lumbar spine (BMD-LS) and the femoral neck (BMD-FN) measured by dual X-ray absorptiometry in rheumatoid arthritis (RA). In 146 patients with RA, the following parameters were investigated: serum levels of ionized calcium, total calcium, vitamin D metabolites 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3), intact parathyroid hormone (iPTH), interleukin-6, osteocalcin, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP); renal excretion of pyridinolin (PYD)- and desoxypyridinolin (DPD)-crosslinks. A total of 30.1% of the patients were hypercalcemic (ionized calcium >1.30 mmol/l). In comparison with normocalcemic patients, those with hypercalcemia had significantly higher ESR (P<0.01) and CRP values (P<0.05) and significantly lower serum levels of both iPTH (P<0.01) and 1,25D3 (P<0.05) and a significantly lower BMD-LS (P<0.05). The results indicate that a substantial part of RA patients is hypercalcemic. Hypercalcemia is associated with high disease activity and may contribute to suppression of PTH secretion and vitamin D hormone synthesis. High levels of ionized calcium may be a reflection of disease-activity-related systemic bone loss, and could be a predictor of BMD at the lumbar spine in RA.
Naunyn-Schmiedeberg's Archives of Pharmacology, 1998
Two types of receptors for gastrin and cholecystokinin (CCK) have been identified in the gastroin... more Two types of receptors for gastrin and cholecystokinin (CCK) have been identified in the gastrointestinal tract and in the central nervous system: CCK(A) and CCK(B) receptors. Here we report evidence for the expression of CCK(B) receptors in the guinea-pig kidney. Specific binding sites for [125I]gastrin were detected in sections of the guinea-pig kidney: Binding was saturable, pH-, temperature- and time-dependent, and specific for gastrin-related peptides. The potencies for inhibition of binding of [125I]gastrin were CCK-8 > gastrin 17-I > CCK(B) receptor antagonist L-365,260 > des(SO3)CCK-8 > CCK(A) receptor antagonist L-364,718. Autoradiography demonstrated specific [125I]gastrin binding to medullary collecting ducts and to a much lesser extent to glomeruli, but not over other structures. CCK(B) receptor cDNA fragments were amplified by RT-PCR from total kidney, isolated tubuli and from tissues known to express CCK(B) receptors such as stomach and brain. The kidney might therefore be a previously unidentified site of action for gastrin and cholecystokinin-related peptides.
The aim of the study was to compare transthoracic sonography (TS) with multislice computed tomogr... more The aim of the study was to compare transthoracic sonography (TS) with multislice computed tomography (MSCT) in the detection of peripheral pulmonary embolism (PE). In addition, the study verified peripheral parenchymal findings visualized by TS and MSCT. A total of 33 patients (16 females, 17 males; mean age = 65.4 years) with symptoms of suspected PE were enrolled in the study. TS and MSCT were undertaken within 24 h of the beginning of clinical PE signs. Ten patients suffered from PE as visualized by MSCT. The sensitivity of TS for detecting PE was 70.0% and the specificity was 69.6%. Preferentially, PE and peripheral parenchymal findings were situated in the lower lobes. Oligemia was the main parenchymal alteration detected by MSCT. TS demonstrated that wedge-shaped consolidations were frequently associated with PE. In addition, localized pleural effusion was a typical finding in the presence of PE for both TS and MSCT. TS had moderate sensitivity and specificity compared with MSCT. Furthermore, the study revealed that PE is often associated with peripheral parenchymal changes, both of which are detectable by TS and MSCT. In case of contraindication with MSCT, TS is a potential technique for diagnosing PE-related parenchymal findings and can serve as an alternative method in the diagnosis of PE. However, a negative result with TS does not rule out a PE.
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