T. Forslund - Academia.edu (original) (raw)
Papers by T. Forslund
[Captopril-a new principle in the treatment of hypertension]
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 1981
Sustained Antihypertensive Effect of Captopril Combined with Diuretics and Beta-adrenergic Blocking Drugs in Patients with Resistant Hypertension
Acta Medica Scandinavica, 2009
Ten patients with severe hypertension and unsatisfactory blood pressure control during combined t... more Ten patients with severe hypertension and unsatisfactory blood pressure control during combined therapy with beta-adrenergic blocking drugs, diuretics, and vasodilators were treated with gradually increasing doses of captopril. Vasodilators were discontinued 24 hours prior to captopril administration. Six patients had essential, two renal, and two renovascular hypertension. Mild renal impairment was observed in four patients. Captopril effectively decreased blood pressure for 3 hours in all patients after the first dose. The antihypertensive effect appeared to be triphasic and was sustained in all but one patient during 12 months of observation. Captopril doses of 25-75 mg t.i.d. were sufficient to achieve acceptable blood pressure control (RR less than or equal to 160/100 mmHg) when given in the above mentioned combination. Side-effects were few and tolerable and discontinuation of captopril was not required.
Plasma Atrial Natriuretic Peptide in Cardiac Transplant Recipients
Acta Medica Scandinavica, 2009
Cardiac transplantation in 10 patients with congestive heart failure resulted in reduction of hig... more Cardiac transplantation in 10 patients with congestive heart failure resulted in reduction of high plasma concentrations of atrial natriuretic peptide (ANP), preoperatively five-fold above normal, to a level two-fold above normal, which was maintained throughout a 12-week follow-up period. Cardiac function was normalized in all patients. Transient increases in plasma ANP, in four cardiac recipients 3-10-fold their basal levels, could neither be related to rejection episodes nor to cardiac dysfunction, but rather to signs of fluid and sodium retention. High plasma ANP levels in cardiac transplant recipients suggest that the capacity to secrete ANP is preserved in the transplanted heart.
European Journal of Pharmacology, 1982
Having observed that treatment of rats with captopril led to an increased ACE activity in serum a... more Having observed that treatment of rats with captopril led to an increased ACE activity in serum and ACE concentration in lungs, we treated female Wistar Kyoto rats for 7 days with the esterified ACE inhibitor, MK-421 (I.0 mg/kg body weight per day), administered by Alzet osmotic minipump. Serum ACE activity decreased by 67% during MK-421 treatment when measured in non-dialyzed serum samples. Removal of the drug by dialysis unmasked a 280% increase of serum ACE activity. ACE concentration of crude lung homogenate increased 134% in MK-421-treated rats and ACE concentration in purified pulmonary plasma membranes increased by 34%. The increase of serum and lung ACE in MK-421-treated rats was similar to that seen in rats treated with captopril, and was probably due to induction of ACE biosynthesis. The mechanisms of this induction are unknown. Angiotensin converting enzyme MK-421 Enzyme induction Kininase 11 Pulmonary plasma membranes
Regulation of angiotensin converting enzyme
Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 1983
Angiotensin converting enzyme (ACE;EC 3.4.15.1), or kininase II, was studied in serum, cultured e... more Angiotensin converting enzyme (ACE;EC 3.4.15.1), or kininase II, was studied in serum, cultured endothelial cells from cord artery, in macrophages of humans, and in serum and purified plasma membranes of rats following treatment with inducers of ACE biosynthesis. ACE activity was measured in biological fluids with an enzyme kinetic method employing synthetic 1-hipp-1-his-l-leu tripeptide as a substrate, and with a new method using 125I-labelled specific inhibitor of ACE as a sensitive probe for ACE binding sites. The latter technique also proved suitable for the quantification of ACE in cells. Anti-human ACE antibody was employed for immunofluorescence studies in human cells. Dexamethasone treatment caused an increase in ACE in cultured human endothelial cells, macrophages and in rat pulmonary plasma membranes, but failed to increase serum ACE activity in rats. Captopril and enalapril treatment of hypertensive patients increased total serum ACE, the increase being evident after remo...
Hormonal changes during tilt and atrial pacing in heart transplant patients
Transplantation proceedings, 1990
Cardiac failure, hepatic congestion and increased level of serum carcinoembryonic antigen
Postgraduate Medical Journal, 1984
A 65-year-old woman undergoing chronic haemodialysis for chronic nephritis had transiently elevat... more A 65-year-old woman undergoing chronic haemodialysis for chronic nephritis had transiently elevated serum carcinoembryonic antigen levels, up to 26 ng/ml for nearly 3 months. This elevation was most probably due to cardiac failure with hepatic congestion and pulmonary oedema, because the antigen level returned to normal when the cardiac failure was properly treated, and comprehensive examinations revealed no other cause.
Teriparatide treatment complicated by malignant myeloma
Case Reports, 2010
Recombinant human parathyroid hormone (1-34) (rhPTH 1-34), teriparatide (Forsteo in Europe), is a... more Recombinant human parathyroid hormone (1-34) (rhPTH 1-34), teriparatide (Forsteo in Europe), is a new compound that has been introduced and shown to be successful in the treatment of osteoporosis. The mechanisms of action include a pulsative influence on the RANKL/OPG system resulting in osteoblast activation and increased bone formation by teriparatide. In malignant myeloma there is an imbalance between osteoclast and osteoblast activity with involvement of the RANKL/OPG system among others. We report a case with monoclonal gammopathy of uncertain significance (MGUS) who developed malignant myeloma after teriparatide treatment and we suggest that in addition to malignant myeloma and smouldering myeloma, MGUS should also be considered contraindicated for teriparatide treatment.
Raised plasma endothelin-1 concentration in patients with nephropathia epidemica
Clinical nephrology, 1993
Nephropathia epidemica (NE) with renal syndrome, caused by the Puumala-virus, is manifested clini... more Nephropathia epidemica (NE) with renal syndrome, caused by the Puumala-virus, is manifested clinically by the triad of fever, hemorrhage and renal failure. We observed raised plasma concentrations of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in 23 patients during the acute phase of NE. They all developed transient renal failure and all displayed characteristics of NE, also verified by a rapid IgG antibody test. Blood pressure was normal or low in all subjects during the acute phase of the disease. Plasma ET-1 and ANP levels returned to normal following recovery one month later. The cause of increased ET-1 synthesis in NE remains unknown. It may be related to vascular damage or extravasation of blood. ET-1 may participate in the pathogenesis of acute renal failure of NE. Raised plasma ANP levels were most likely caused by fluid retention during the acute phase of NE. However, high levels of circulating ET-1 might have contributed to increased release of ANP.
Kidney transplantation and tumours
Annals of clinical research, 1980
During the period 1964--1978 700 renal transplants were given to 602 patients. Eight patients had... more During the period 1964--1978 700 renal transplants were given to 602 patients. Eight patients had a history of tumour before transplantation. After transplantation six cases with a de novo tumour were found. The treatment of the pretransplant tumours was completed on average 3 years before transplantation. The average interval from transplantation to discovery of de novo tumour was 2 years. The pretransplant tumours appeared 5 to 9 years before last control (Jan. 79) (mean 8 years). Two of the transplanted patients with previous tumours died later of their tumours. The others are still alive. Two of the patients with de novo tumour died of vascular accidents and one of tumour. The other three are alive. It seems that transplantation can be successful in patients with previous tumours. This study does not support previous reports of increased risk of de novo tumours in transplanted patients.
Renin, renin substrate, angiotensin II, and vasopressin in plasma during treatment with captopril in hypertension and heart failure
Acta medica Scandinavica. Supplementum, 1983
Increase of serum and membrane-bound angiotensin-converting enzyme by captopril (SQ 14225) treatment
Acta medica Scandinavica. Supplementum, 1983
Acta pharmacologica et toxicologica, 1981
Spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain (n = 40) were treated with capto... more Spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain (n = 40) were treated with captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) orally, dose 0.2 mg/ml in drinking water. The treatment was initiated early and later during the course of developing hypertension. Continuously treated rats did not develop hypertension. Rats receiving captopril for 12 weeks remained normotensive, whereas withdrawal of the drug resulted in hypertension. Captopril treatment was effective in the rats with established hypertension and decreased the blood pressures to nearly normal values. Serum angiotensin converting enzyme (ACE) activity rose 3-fold in captopril treated rats. ACE in lung plasma membranes increased during captopril treatment, indicating that captopril induced biosynthesis of pulmonary ACE. No qualitative differences were found in the ACE from treated and not treated animals. The dissociation of the antihypertensive effect of captopril and of increased ACE activity ...
Induction of angiotensin I-converting enzyme rat lung with Captopril (SQ 14225)
European journal of pharmacology, Jan 31, 1980
Angiotensin I-converting enzyme (ACE, EC 2.4.15.1.) was measured in serum and in pulmonary plasma... more Angiotensin I-converting enzyme (ACE, EC 2.4.15.1.) was measured in serum and in pulmonary plasma membranes of 40 spontaneously hypertensive rats (SHR, Okamoto Aoki strain), divided into 4 groups, and treated with SQ 14225 (Captopril), 0.2 mg . ml-1 in drinking water, for 0-24 weeks. Serum ACE activity increased 2.5-3 fold after 12-24 weeks of SQ 14225 treatment, paralleled by an increase of ACE concentration in purified pulmonary plasma membranes (25-52%), and in ACE concentration upon solubilization with Triton X-100 from such plasma membranes (96-120%). We conclude that the ACE inhibitor, SQ 14225, causes marked induction of pulmonary ACE biosynthesis. High serum ACE activity probably reflects increased total biosynthesis of the enzyme.
[Epidemic nephritis followed by hypogonadism]
Duodecim; lääketieteellinen aikakauskirja, 1992
Acta Pharmacologica et Toxicologica, 1983
The effect of treatment time and dose of captopril with regard to angiotensin converting enzyme (... more The effect of treatment time and dose of captopril with regard to angiotensin converting enzyme (ACE) in serum, lungs and kidneys of the rat were studied. Normotensive Wistar rats were treated with a constant dose of captopril (0.2 mg/ml) during various time periods. In a second study rats were treated with different captopril doses (6.25 pg, 12.5 pg, 25 pg, 50 pg, and 200 pg/ml water) during three weeks. Serum ACE activity and pulmonary and kidney plasma membrane ACE concentrations were measured in both studies. Captopril treatment resulted in a rapid decrease of ACE in pulmonary and kidney plasma membranes and a simultaneously increase of serum ACE activity during the first day of treatment. This was followed by increased membrane concentrations of ACE in the lungs and return to normal ACE concentrations in membranes of kidneys, presumably due to increased ACE biosynthesis. Serum ACE activity continued to increase during the whole study. Serum ACE activity increased in a dose dependent manner during treatment with different captopril doses. Increased plasma membrane ACE concentrations were not observed in the rats treated with captopril at doses below 200 pg/ml water.
Acta Pharmacologica et Toxicologica, 1983
Serum ACE activity increased as expected about three-fold following six weeks of captopril (30 mg... more Serum ACE activity increased as expected about three-fold following six weeks of captopril (30 mg/kg/day) treatment in Wistar rats (n=9). The effect on serum and lung ACE activity and concentration, respectively, was studied after captopril discontinuation. Serum ACE activity was measured at start and 3, 6 , and 12 days after captopril withdrawal. The approximal half-life of serum ACE activity was 72 hours as judged from the decrease rate after stimulated ACE biosynthesis induced by captopril. No differences in lung plasma membranes and lung homogenate ACE concentrations between treated and untreated rats were observed 12 days after discontinuation of captopril treatment. Serum ACE activity remained unchanged in the control rats (n=9). We conclude that induction of ACE biosynthesis in the rat is reversible after withdrawal of captopril.
Tissue Distribution of Angiotensin Converting Enzyme in the Rat: Effect of Captopril Treatment
Acta Pharmacologica et Toxicologica, 1984
Effect on different tissues with regard to angiotensin converting enzyme during captopril treatme... more Effect on different tissues with regard to angiotensin converting enzyme during captopril treatment in the rat was studied. Male Wistar-Kyoto rats (n = 9) were treated during four weeks with captopril dissolved into the drinking water at the dose 30 mg/kg/day. Control rats (n = 9) had water only. Serum angiotensin converting enzyme (ACE) activity increased three-fold during captopril treatment, and ACE of purified pulmonary plasma membranes increased about 64% (P less than 0.001) compared to untreated rats. ACE activity of membrane fractions of other tissues studied i.e. testicles, epididymes, kidneys, and small intestine brush border did not increase similarly during captopril treatment. The highest amounts of ACE was demonstrated in epididymes, but captopril did not produce increased amounts of ACE in the epididymes. The main source of increased serum ACE activity during captopril treatment appeared to be in the pulmonary tissue.
The Use of Pretransplant Erythropoietin to Normalize Hemoglobin Levels Has No Deleterious Effects on Renal Transplantation OUTCOME1
Transplantation, 2001
The aim of this study was to establish the outcome of renal transplantation in patients given pre... more The aim of this study was to establish the outcome of renal transplantation in patients given pretransplant erythropoietin (EPO) treatment targeted at reaching a normal hemoglobin concentration (Hb), compared to those given EPO-treatment aimed at maintaining subnormal Hb. A total of 416 patients from Scandinavian countries and with renal anaemia were enrolled to examine the effects of increasing Hb from a subnormal level (90-120 g/liter) to a normal level (135-160 g/liter) by EPO treatment. Half of the patients were randomized to have their Hb increased, with the other half randomized to maintain a subnormal Hb. Thirty-two patients from the normal Hb group and 24 patients from the subnormal group received a renal graft during the study period. The outcomes of these transplantations were examined prospectively for 6 months. Preoperative Hb levels were 143+/-17 and 121+/-14 g/liter in the two groups, respectively (P<0.0001). The Hb remained higher in the normal Hb group during the first 2 weeks after transplantation. The percentage of patients requiring postoperative blood transfusions in the normal Hb group was 16%, compared with 50% in the subnormal group (P<0.01). No statistically significant difference in the proportion of functioning grafts or in the serum creatinine levels could be detected. No correlation between EPO treatment and creatinine levels after transplantation was found. The frequency of adverse events was similar in the two groups. EPO treatment aimed at reaching a normal Hb in renal transplant recipients reduces the postoperative requirement for blood transfusions and has no deleterious effects on kidney graft function.
IgA nephropathy in a patient with IgG lambda light-chain plasmacytoma: a rare coincidence
Nephrology Dialysis Transplantation, 2007
[Captopril-a new principle in the treatment of hypertension]
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 1981
Sustained Antihypertensive Effect of Captopril Combined with Diuretics and Beta-adrenergic Blocking Drugs in Patients with Resistant Hypertension
Acta Medica Scandinavica, 2009
Ten patients with severe hypertension and unsatisfactory blood pressure control during combined t... more Ten patients with severe hypertension and unsatisfactory blood pressure control during combined therapy with beta-adrenergic blocking drugs, diuretics, and vasodilators were treated with gradually increasing doses of captopril. Vasodilators were discontinued 24 hours prior to captopril administration. Six patients had essential, two renal, and two renovascular hypertension. Mild renal impairment was observed in four patients. Captopril effectively decreased blood pressure for 3 hours in all patients after the first dose. The antihypertensive effect appeared to be triphasic and was sustained in all but one patient during 12 months of observation. Captopril doses of 25-75 mg t.i.d. were sufficient to achieve acceptable blood pressure control (RR less than or equal to 160/100 mmHg) when given in the above mentioned combination. Side-effects were few and tolerable and discontinuation of captopril was not required.
Plasma Atrial Natriuretic Peptide in Cardiac Transplant Recipients
Acta Medica Scandinavica, 2009
Cardiac transplantation in 10 patients with congestive heart failure resulted in reduction of hig... more Cardiac transplantation in 10 patients with congestive heart failure resulted in reduction of high plasma concentrations of atrial natriuretic peptide (ANP), preoperatively five-fold above normal, to a level two-fold above normal, which was maintained throughout a 12-week follow-up period. Cardiac function was normalized in all patients. Transient increases in plasma ANP, in four cardiac recipients 3-10-fold their basal levels, could neither be related to rejection episodes nor to cardiac dysfunction, but rather to signs of fluid and sodium retention. High plasma ANP levels in cardiac transplant recipients suggest that the capacity to secrete ANP is preserved in the transplanted heart.
European Journal of Pharmacology, 1982
Having observed that treatment of rats with captopril led to an increased ACE activity in serum a... more Having observed that treatment of rats with captopril led to an increased ACE activity in serum and ACE concentration in lungs, we treated female Wistar Kyoto rats for 7 days with the esterified ACE inhibitor, MK-421 (I.0 mg/kg body weight per day), administered by Alzet osmotic minipump. Serum ACE activity decreased by 67% during MK-421 treatment when measured in non-dialyzed serum samples. Removal of the drug by dialysis unmasked a 280% increase of serum ACE activity. ACE concentration of crude lung homogenate increased 134% in MK-421-treated rats and ACE concentration in purified pulmonary plasma membranes increased by 34%. The increase of serum and lung ACE in MK-421-treated rats was similar to that seen in rats treated with captopril, and was probably due to induction of ACE biosynthesis. The mechanisms of this induction are unknown. Angiotensin converting enzyme MK-421 Enzyme induction Kininase 11 Pulmonary plasma membranes
Regulation of angiotensin converting enzyme
Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 1983
Angiotensin converting enzyme (ACE;EC 3.4.15.1), or kininase II, was studied in serum, cultured e... more Angiotensin converting enzyme (ACE;EC 3.4.15.1), or kininase II, was studied in serum, cultured endothelial cells from cord artery, in macrophages of humans, and in serum and purified plasma membranes of rats following treatment with inducers of ACE biosynthesis. ACE activity was measured in biological fluids with an enzyme kinetic method employing synthetic 1-hipp-1-his-l-leu tripeptide as a substrate, and with a new method using 125I-labelled specific inhibitor of ACE as a sensitive probe for ACE binding sites. The latter technique also proved suitable for the quantification of ACE in cells. Anti-human ACE antibody was employed for immunofluorescence studies in human cells. Dexamethasone treatment caused an increase in ACE in cultured human endothelial cells, macrophages and in rat pulmonary plasma membranes, but failed to increase serum ACE activity in rats. Captopril and enalapril treatment of hypertensive patients increased total serum ACE, the increase being evident after remo...
Hormonal changes during tilt and atrial pacing in heart transplant patients
Transplantation proceedings, 1990
Cardiac failure, hepatic congestion and increased level of serum carcinoembryonic antigen
Postgraduate Medical Journal, 1984
A 65-year-old woman undergoing chronic haemodialysis for chronic nephritis had transiently elevat... more A 65-year-old woman undergoing chronic haemodialysis for chronic nephritis had transiently elevated serum carcinoembryonic antigen levels, up to 26 ng/ml for nearly 3 months. This elevation was most probably due to cardiac failure with hepatic congestion and pulmonary oedema, because the antigen level returned to normal when the cardiac failure was properly treated, and comprehensive examinations revealed no other cause.
Teriparatide treatment complicated by malignant myeloma
Case Reports, 2010
Recombinant human parathyroid hormone (1-34) (rhPTH 1-34), teriparatide (Forsteo in Europe), is a... more Recombinant human parathyroid hormone (1-34) (rhPTH 1-34), teriparatide (Forsteo in Europe), is a new compound that has been introduced and shown to be successful in the treatment of osteoporosis. The mechanisms of action include a pulsative influence on the RANKL/OPG system resulting in osteoblast activation and increased bone formation by teriparatide. In malignant myeloma there is an imbalance between osteoclast and osteoblast activity with involvement of the RANKL/OPG system among others. We report a case with monoclonal gammopathy of uncertain significance (MGUS) who developed malignant myeloma after teriparatide treatment and we suggest that in addition to malignant myeloma and smouldering myeloma, MGUS should also be considered contraindicated for teriparatide treatment.
Raised plasma endothelin-1 concentration in patients with nephropathia epidemica
Clinical nephrology, 1993
Nephropathia epidemica (NE) with renal syndrome, caused by the Puumala-virus, is manifested clini... more Nephropathia epidemica (NE) with renal syndrome, caused by the Puumala-virus, is manifested clinically by the triad of fever, hemorrhage and renal failure. We observed raised plasma concentrations of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in 23 patients during the acute phase of NE. They all developed transient renal failure and all displayed characteristics of NE, also verified by a rapid IgG antibody test. Blood pressure was normal or low in all subjects during the acute phase of the disease. Plasma ET-1 and ANP levels returned to normal following recovery one month later. The cause of increased ET-1 synthesis in NE remains unknown. It may be related to vascular damage or extravasation of blood. ET-1 may participate in the pathogenesis of acute renal failure of NE. Raised plasma ANP levels were most likely caused by fluid retention during the acute phase of NE. However, high levels of circulating ET-1 might have contributed to increased release of ANP.
Kidney transplantation and tumours
Annals of clinical research, 1980
During the period 1964--1978 700 renal transplants were given to 602 patients. Eight patients had... more During the period 1964--1978 700 renal transplants were given to 602 patients. Eight patients had a history of tumour before transplantation. After transplantation six cases with a de novo tumour were found. The treatment of the pretransplant tumours was completed on average 3 years before transplantation. The average interval from transplantation to discovery of de novo tumour was 2 years. The pretransplant tumours appeared 5 to 9 years before last control (Jan. 79) (mean 8 years). Two of the transplanted patients with previous tumours died later of their tumours. The others are still alive. Two of the patients with de novo tumour died of vascular accidents and one of tumour. The other three are alive. It seems that transplantation can be successful in patients with previous tumours. This study does not support previous reports of increased risk of de novo tumours in transplanted patients.
Renin, renin substrate, angiotensin II, and vasopressin in plasma during treatment with captopril in hypertension and heart failure
Acta medica Scandinavica. Supplementum, 1983
Increase of serum and membrane-bound angiotensin-converting enzyme by captopril (SQ 14225) treatment
Acta medica Scandinavica. Supplementum, 1983
Acta pharmacologica et toxicologica, 1981
Spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain (n = 40) were treated with capto... more Spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain (n = 40) were treated with captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) orally, dose 0.2 mg/ml in drinking water. The treatment was initiated early and later during the course of developing hypertension. Continuously treated rats did not develop hypertension. Rats receiving captopril for 12 weeks remained normotensive, whereas withdrawal of the drug resulted in hypertension. Captopril treatment was effective in the rats with established hypertension and decreased the blood pressures to nearly normal values. Serum angiotensin converting enzyme (ACE) activity rose 3-fold in captopril treated rats. ACE in lung plasma membranes increased during captopril treatment, indicating that captopril induced biosynthesis of pulmonary ACE. No qualitative differences were found in the ACE from treated and not treated animals. The dissociation of the antihypertensive effect of captopril and of increased ACE activity ...
Induction of angiotensin I-converting enzyme rat lung with Captopril (SQ 14225)
European journal of pharmacology, Jan 31, 1980
Angiotensin I-converting enzyme (ACE, EC 2.4.15.1.) was measured in serum and in pulmonary plasma... more Angiotensin I-converting enzyme (ACE, EC 2.4.15.1.) was measured in serum and in pulmonary plasma membranes of 40 spontaneously hypertensive rats (SHR, Okamoto Aoki strain), divided into 4 groups, and treated with SQ 14225 (Captopril), 0.2 mg . ml-1 in drinking water, for 0-24 weeks. Serum ACE activity increased 2.5-3 fold after 12-24 weeks of SQ 14225 treatment, paralleled by an increase of ACE concentration in purified pulmonary plasma membranes (25-52%), and in ACE concentration upon solubilization with Triton X-100 from such plasma membranes (96-120%). We conclude that the ACE inhibitor, SQ 14225, causes marked induction of pulmonary ACE biosynthesis. High serum ACE activity probably reflects increased total biosynthesis of the enzyme.
[Epidemic nephritis followed by hypogonadism]
Duodecim; lääketieteellinen aikakauskirja, 1992
Acta Pharmacologica et Toxicologica, 1983
The effect of treatment time and dose of captopril with regard to angiotensin converting enzyme (... more The effect of treatment time and dose of captopril with regard to angiotensin converting enzyme (ACE) in serum, lungs and kidneys of the rat were studied. Normotensive Wistar rats were treated with a constant dose of captopril (0.2 mg/ml) during various time periods. In a second study rats were treated with different captopril doses (6.25 pg, 12.5 pg, 25 pg, 50 pg, and 200 pg/ml water) during three weeks. Serum ACE activity and pulmonary and kidney plasma membrane ACE concentrations were measured in both studies. Captopril treatment resulted in a rapid decrease of ACE in pulmonary and kidney plasma membranes and a simultaneously increase of serum ACE activity during the first day of treatment. This was followed by increased membrane concentrations of ACE in the lungs and return to normal ACE concentrations in membranes of kidneys, presumably due to increased ACE biosynthesis. Serum ACE activity continued to increase during the whole study. Serum ACE activity increased in a dose dependent manner during treatment with different captopril doses. Increased plasma membrane ACE concentrations were not observed in the rats treated with captopril at doses below 200 pg/ml water.
Acta Pharmacologica et Toxicologica, 1983
Serum ACE activity increased as expected about three-fold following six weeks of captopril (30 mg... more Serum ACE activity increased as expected about three-fold following six weeks of captopril (30 mg/kg/day) treatment in Wistar rats (n=9). The effect on serum and lung ACE activity and concentration, respectively, was studied after captopril discontinuation. Serum ACE activity was measured at start and 3, 6 , and 12 days after captopril withdrawal. The approximal half-life of serum ACE activity was 72 hours as judged from the decrease rate after stimulated ACE biosynthesis induced by captopril. No differences in lung plasma membranes and lung homogenate ACE concentrations between treated and untreated rats were observed 12 days after discontinuation of captopril treatment. Serum ACE activity remained unchanged in the control rats (n=9). We conclude that induction of ACE biosynthesis in the rat is reversible after withdrawal of captopril.
Tissue Distribution of Angiotensin Converting Enzyme in the Rat: Effect of Captopril Treatment
Acta Pharmacologica et Toxicologica, 1984
Effect on different tissues with regard to angiotensin converting enzyme during captopril treatme... more Effect on different tissues with regard to angiotensin converting enzyme during captopril treatment in the rat was studied. Male Wistar-Kyoto rats (n = 9) were treated during four weeks with captopril dissolved into the drinking water at the dose 30 mg/kg/day. Control rats (n = 9) had water only. Serum angiotensin converting enzyme (ACE) activity increased three-fold during captopril treatment, and ACE of purified pulmonary plasma membranes increased about 64% (P less than 0.001) compared to untreated rats. ACE activity of membrane fractions of other tissues studied i.e. testicles, epididymes, kidneys, and small intestine brush border did not increase similarly during captopril treatment. The highest amounts of ACE was demonstrated in epididymes, but captopril did not produce increased amounts of ACE in the epididymes. The main source of increased serum ACE activity during captopril treatment appeared to be in the pulmonary tissue.
The Use of Pretransplant Erythropoietin to Normalize Hemoglobin Levels Has No Deleterious Effects on Renal Transplantation OUTCOME1
Transplantation, 2001
The aim of this study was to establish the outcome of renal transplantation in patients given pre... more The aim of this study was to establish the outcome of renal transplantation in patients given pretransplant erythropoietin (EPO) treatment targeted at reaching a normal hemoglobin concentration (Hb), compared to those given EPO-treatment aimed at maintaining subnormal Hb. A total of 416 patients from Scandinavian countries and with renal anaemia were enrolled to examine the effects of increasing Hb from a subnormal level (90-120 g/liter) to a normal level (135-160 g/liter) by EPO treatment. Half of the patients were randomized to have their Hb increased, with the other half randomized to maintain a subnormal Hb. Thirty-two patients from the normal Hb group and 24 patients from the subnormal group received a renal graft during the study period. The outcomes of these transplantations were examined prospectively for 6 months. Preoperative Hb levels were 143+/-17 and 121+/-14 g/liter in the two groups, respectively (P<0.0001). The Hb remained higher in the normal Hb group during the first 2 weeks after transplantation. The percentage of patients requiring postoperative blood transfusions in the normal Hb group was 16%, compared with 50% in the subnormal group (P<0.01). No statistically significant difference in the proportion of functioning grafts or in the serum creatinine levels could be detected. No correlation between EPO treatment and creatinine levels after transplantation was found. The frequency of adverse events was similar in the two groups. EPO treatment aimed at reaching a normal Hb in renal transplant recipients reduces the postoperative requirement for blood transfusions and has no deleterious effects on kidney graft function.
IgA nephropathy in a patient with IgG lambda light-chain plasmacytoma: a rare coincidence
Nephrology Dialysis Transplantation, 2007