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Biomedical subjects

E B Pedersen

Publications and source records attributed to E B Pedersen.

359 records · Page 20Linked to original sources
PubMed1975

Glomerular filtration rate and renal plasma flow in patients with essential hypertension before and after treatment with alprenolol.

In 25 patients with essential hypertension, the renal plasma flow RPF), glomerular filtration rate (GFR) and BP have been measured before and after one month's treatment with alprenolol. The patients were divided into two groups according to age. Group 1 consisted of 10 patients with mild hypertension under 35 years of age, group 2 of 15 patients over the age of 35 with moderate hypertension. A markedly greater lowering of BP was measured in group 1 than in group 2. There were no changes in RPF or GFR after alprenolol treatment and no differences in these parameters were observed between the two groups either before or after treatment. Group 1 displayed significantly lower renal vascular resistance (RVR) than group 2 both before and after treatment, and alprenolol treatment resulted in a slight reduction of RVR in group 1, but not in group 2. The difference between the two groups with respect to the antihypertensive effect of alprenolol and the RVR may possibly be due to the fact that the patients in group 2 had more pronounced structural vascular alterations than those in group 1.

Adult↗
PubMed1975

Catecholamines in plasma and urine in patients with essential hypertension determined by double-isotope derivative techniques.

Employing double-isotope derivative techniques, noradrenaline and adrenaline have been determined in plasma and in urine and dopamine in urine in 21 patients with essential hypertension as well as in 32 controls. Plasma noradrenaline rose with age in both groups of subjects. No differences were observed in plasma noradrenaline and plasma adrenaline in the resting supine position and in urinary excretion of noradrenaline and dopamine in hypertensive patients as compared to control subjects. Urinary excretion of adrenaline was somewhat lower in the hypertensives than in the controls. Treatment with alprenolol, a beta-adrenergic blocking agent, did not influence noradrenaline and adrenaline in plasma in the basal state or the urinary excretion of the three catecholamines. The combined treatment with alprenolol and hydralazine was followed by a significant rise in plasma noradrenaline. It is concluded that the adrenergic activity evaluated by circulating catecholamines is normal in most patients with essential hypertension.

Adult↗
PubMed1975

Effect of alprenolol and hydralazine on plasma renin concentration in patients with arterial hypertension.

The effect of alprenolol alone and in combination with hydralazine on plasma renin concentration has been studied in 25 patients with arterial hypertension. Alprenolol caused a significant fall in plasma renin concentration and in BP but the two falls were not intercorrelated. Addition of hydralazine to the treatment regimen produced a further reduction of BP. Changes in plasma renin concentration varied greatly during combination therapy. A modest, non-significant increase in plasma renin concentration was measured compared with the level after treatment with alprenolol. It is concluded that mechanisms other than suppression of plasma renin concentration are important for the reduction of BP during beta-adrenergic blockade and that the plasma renin concentration probably has no clinical significance with regard to forecasting the antihypertensive effect of alprenolol. Even though a significant correlation was found between the fall in plasma renin concentration and the fall in diastolic BP during combination therapy, it is uncertain whether changes in the renin-angiotensin system are of primary importance for BP regulation during this therapy.

Adult↗
PubMedDate not supplied

The potential of aspirin in prodrug synthesis: a new potential delivery system of AZT and FLT.

Aspirin (O-acetylsalicylic acid) has been used to synthesize prodrugs of 3'-azido-3'-deoxythymidine (AZT) and 3'-deoxy-3'-fluorothymidine (FLT). The mixed anhydride between aspirin and trifluoroacetic acid was synthesized and reacted with AZT and FLT to give the blocked nucleosides attached through the 5'-O position to the 2-position of 2-methyl-4H-1,3-benzodioxin-4-one. The prodrugs showed the same activities against HIV-1 in MT-4 cells as the original drugs. Hydrolysis of the synthesized prodrugs in the growth medium, used for anti-HIV investigations, resulted in formation of 5-O acetylated drugs which were subsequently hydrolyzed into the original drugs.

Antiviral Agents↗
PubMedDate not supplied

Bisintercalation of homodimeric thiazole orange dyes in DNA: effect of modifying the linker.

The thiazole orange dye 1,1'-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-bis[4-[3-methy l-2, 3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO) binds to double-stranded DNA (dsDNA) in a sequence selective bisintercalation. Each chromophore is sandwiched between two base pairs in a (5'-CpT-3'):(5'-ApG-3') site, and the linker spans over two base pairs in the minor groove. The binding of analogs of TOTO in which the linker has been modified is examined. The aim of the study is to utilize the sequence selectivity of the TOTO chromophores to enhance and/or alter the overall selectivity of the binding. One- and two-dimensional 1H-NMR investigations of complexes between TOTO analogs and various dsDNA oligonucleotides are reported. The following analogs were synthesized and used: 1,1'-(4,4,8,8-tetramethyl-4,8-diazadodecamethylene) -bis[4-[3-methyl-2,3-dihydro- (benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO10), 1,1'-(5,5,9,9-tetramethyl-5,9-diazatridecamethylene)-bis[4-[3-meth yl-2, 3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO11), and 1,1'-(6,6,10,10-tetramethyl-6,10-diazapentadecamethylene)-bis[4-[3 -methyl-2, 3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO13). The results show that with a longer linker the dyes can bisintercalate into two (5'-CpT-3'):(5'-ApG-3') sites separated by one or two base pairs. Bisintercalation in two such "isolated" binding sites yields non-nearest-neighbor bisintercalation in which the linker spans over more than two base pairs. The investigations also showed that an exact length of the linker is not crucial for the site selectivity since TOTO, TOTO10, and TOTO11 are almost equally suitable in binding selectively to the (5'CTAG-3')2 sequence. Fluorescence measurements show that TOTO10, TOTO11, and TOTO13 have higher fluorescence quantum yields than TOTO when bound to d(CGCTAGCG)2. This indicates that the length of the linker in TOTO may not be the optimum one in terms of using the dye as a fluorescence marker.

Benzothiazoles↗
PubMedDate not supplied

Bis-intercalation of homodimeric thiazole orange dye derivatives in DNA.

The thiazole orange dye 1,1'-(4,4,8,8-tetramethyl-4, 8-diazaundecamethylene)-bis-4-[(3-methyl-2,3-dihydro-2(3H)-benzo-1 ,3-thiazolylidene)methyl]quinolinium tetraiodide (TOTO) binds to double-stranded DNA (dsDNA) in a sequence selective bis-intercalation. We have examined the binding of derivatives of TOTO with different substituents on the benzothiazole ring. The analogues are the following: 1,1'-(4,4,8,8-tetramethyl-4, 8-diazaundecamethylene)-[4-[3-(benzyl-2, 3-dihydro-2-(3H)-benzothiazolylidene)methyl]quinolinium]-[4-[3-(++ +methy l-2, 3-dihydro-2-(3H)-benzothiazolylidene)methyl]quinolinium]tetraio dide (TOTOBzl) and 1,1'-(4,4,8,8-tetramethyl-4, 8-diazaundecamethylene)-bis-4-[(3-ethyl-2,3-dihydro-2(3H)-benzo-1, 3-thiazole)methyl]quinolinium tetraiodide (TOTOEt). In this paper, we report the synthesis of TOTOBzl and TOTOEt together with the one- and two-dimensional 1H NMR investigations of complexes between these TOTO analogues and the dsDNA oligonucleotide d(CGCTAGCG)2. Both analogues yield extremely stable complexes in which each chromophore is sandwiched between two base pairs in a (5'-CpT-3'):(5'-ApG-3') site. The linker spans over two base pairs in the minor groove. The benzyl group in TOTOBzl and the ethyl groups in TOTOEt is pointing outward in the major groove.

Benzothiazoles↗
PubMedDate not supplied

Preparation of oligodeoxynucleotides containing 5-(N-methylpiperazinyl) and 5-benzyloxymethyl uracils.

Deprotected compounds 1 and 9 were allowed to react with 4,4'-dimethoxytrityl chloride in pyridine to give 5'-O-DMT nucleosides 2 and 10. The 3'-phosphoramidites 4 and 11 were incorporated into oligodeoxynucleosides (ODNs). The hybridization properties of the modified ODNs with their complementary DNA strands were studied. Interesting results were obtained when 11 was inserted as a bulged nucleoside into TWAs, duplexes, and triplexes.

Benzyl Compounds↗
PubMedDate not supplied

Estrogen receptors are present in neocortical transplants.

Fetal neocortical tissue was grafted into neocortical lesion cavities made in newborn rats. After two weeks survival, in vitro binding of [3H]-estradiol to cytosolic preparations provided evidence of estrogen receptors within the transplants. The observed high levels correspond to previous work demonstrating elevated estrogen receptor levels during the first postnatal week in the rat cerebral cortex.

Animals↗
PubMedDate not supplied

Preeclampsia -- a state of prostaglandin deficiency? Urinary prostaglandin excretion, the renin-aldosterone system, and circulating catecholamines in preeclampsia.

Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin, aldosterone, norepinephrine (NE) and epinephrine (E) were determined during pregnancy, 5 days, 3, and 6 months after delivery in preeclampsia, normotensive pregnant, and nonpregnant control subjects. The PGE2 was higher in normotensive pregnant control subjects than in nonpregnant subjects. In preeclampsia, PGE2 was reduced to nonpregnant level. PGF2 alpha was the same in preeclampsia and in normotensive pregnancy, but elevated when compared to the normotensive nonpregnant control group. Plasma concentrations of renin and aldosterone were increased during pregnancy, but considerably less in preeclampsia than during normotensive pregnancy. NE and E were the same as in nonpregnant subjects during both hypertensive and normotensive pregnancy. All parameters were normal 3 months after delivery. There were no correlations between PGE2, PGF2 alpha, plasma concentrations of renin, aldosterone, NE, or E and blood pressure level in third trimester either in preeclampsia or in normotensive pregnancy. PGE2 was positively correlated to plasma concentrations of renin. It is suggested that the lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion. It is hypothesized that preeclampsia is a state of prostaglandin deficiency. The changes in the renin-aldosterone system may be secondary to changes in prostaglandin concentration both in preeclampsia and normotensive pregnancy.

Aldosterone↗
PubMedDate not supplied

Increase in plasma renin in aggressive mice originates from kidneys, submaxillary and other salivary glands, and bites.

Aggressive behavior in mice caused a vast release of renin into the plasma. The present data support previous findings that the main sources were the submaxillary gland and kidney. In addition, unidentified salivary glands capable of releasing renin into the saliva were demonstrated by alpha-adrenergic stimulation. The role of these glands in generating plasma renin is unknown. Experiments were performed that strongly support the possibility that aggression-provoked salivary renin may be transferred by bites from one animal to another.

Aggression↗
PubMedDate not supplied

The DaNeX study of embryonic mesencephalic, dopaminergic tissue grafted to a minipig model of Parkinson's disease: preliminary findings of effect of MPTP poisoning on striatal dopaminergic markers.

A multicenter study is under way to investigate the efficacy of allografting of embryonic mesencephalic neurons in a pig model of Parkinson's disease. We have first established that a stable parkinsonian syndrome can be established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication of adult male Göttingen minipigs. We are now using positron emission tomography (PET) methods for testing the physiological responses to MPTP intoxication and the time course of the response to several treatment strategies. We now report preliminary results obtained in 11 pigs employed in the initial phase of the study; the completed study shall ultimately include 30 pigs. Animals were randomly assigned to one of five groups: 1) Control, 2) MPTP intoxication, 3) MPTP intoxication followed by allograft, 4) MPTP intoxication followed by allograft with immunosuppression, and 5) MPTP intoxication followed by allograft with immunosuppression and co-grafting of immortalized HiB5 cells, which had been manipulated to secrete glia cell line-derived neurotrophic factor (GDNF) (approximately 2 ng GDNF/h/10(5) cells). MPTP was administered (1 mg/kg/day, SC) for 7-10 days until the pigs had developed mild parkinsonian symptoms of muscle rigidity, hypokinesia, and impaired coordination, especially of the hind limbs. Approximately 2 weeks after the last MPTP dose, animals received a T1-weighted magnetic resonance imaging (MRI) scan, and a series of dynamic PET recordings. After the first series of PET scans, four grafts of porcine embryonic mesencephalic tissue (E28 days) were placed in each striatum of some MPTP-intoxicated pigs, using MRI-based stereotactic techniques. Immunosuppression of some animals with cyclosporin and prednisolone began just prior to surgery. Two more series of PET scans were performed at 4-month intervals after surgery. After the last scans, pigs were killed and the brains were perfused for unbiased stereological examination of cytological and histochemical markers in striatum and substantial nigra. The behavioral impairment of the animals (the "Parkinson's score") had been evaluated throughout the 8-month period. Kinetic analysis of the first set of PET scans has indicated that the rate constant for the decarboxylation of FDOPA in catecholamine fibers was reduced by 33% in striatum of the mildly parkinsonian pigs. The rate of association of [11C]NS-2214 to catecholamine uptake sites was reduced by 62% in the same groups of pigs. No significant difference was found in the binding potential of [11C]raclopride to the dopamine D2-like receptors in striatum of the MPTP-intoxicated versus control pigs. These preliminary results are suggestive that the activity of DOPA decarboxylase may be upregulated in the partially denervated pig striatum.

Animals↗
PubMedDate not supplied

Proliferative response of human T lymphocytes to porcine fetal brain cells.

Intracerebral grafting of porcine fetal brain cells is a potential treatment of neurodegenerative disorders in humans. Although it is well known that the survival of fetal pig brain cells in the rat brain requires immunosuppression, the response of human T lymphocytes to fetal pig brain cells is unknown. Here we report on the proliferative response of human T lymphocytes to freshly isolated cells and 14-18 days cultured cells from 28- or 35-day-old porcine fetal brains. After 5 days of mixed lymphocyte-brain cell culture, we observed no or only minor T cell responses to the freshly isolated brain cells, while both CD4 cells and CD8 cells proliferated in response to the cultured brain cells. Pretreatment of the cultured brain cells with heat-inactivated human serum significantly reduced the proliferative T cell response. The data suggest that the porcine fetal brain contains cells that can stimulate the human cellular immune system, and that this stimulation may be reduced by pretreatment of the fetal pig brain cells with human serum.

Animals↗
PubMedDate not supplied

Lack of effect of short-term depletion of plasma complement C3 on the survival of syngeneic dopaminergic neurons following grafting into the intact rat striatum.

Metabolically compromised cells may be subject to complement-mediated cytotoxicity. The aim of this study was to clarify to what extent plasma complement C3 might contribute to the low survival (5-20%) of grafted dopaminergic neurons. The survival of intrastriatal cell suspension grafts of syngeneic dopaminergic, tyrosine hydroxylase (TH)-containing neurons was compared in rats subjected to short-term i.v. treatment with 1) cobra venom factor (CVF), or 2) placebo treatment. Depletion of plasma complement C3 by CVF was confirmed by crossed immunoelectrophoresis. With 159 +/- 37 (mean +/- SEM) TH-immunoreactive and 154 + /- 40 TH mRNA-expressing neurons in the CVF-treated rats (n = 9), and 117 +/- 34 TH-immunoreactive and 160 +/- 49 TH mRNA-expressing neurons in placebo rats (n = 6), the CVF treatment did not increase the survival of the grafted dopaminergic neurons. Similarly, CVF had no apparent effect on the astroglial, microglial, or oligodendroglial cell response within and around the graft. The data indicate that depletion of plasma complement C3 at the time of grafting has no effect on the long-term survival of syngeneic ventral mesencephalic dopaminergic neuronal grafts.

Animals↗
PubMedDate not supplied

Effects of captopril on ambulatory blood pressure, renal and cardiac function in microalbuminuric type 1 diabetic patients.

OBJECTIVE: To study the effect of Captopril on ambulatory blood pressure, renal and cardiac function and extracellular volume in microalbuminuric Type 1 diabetic patients. DESIGN: Randomized, double blind placebo controlled study of two years duration. SETTING: University clinic. PATIENTS: Twenty-two patients without hypertension. INTERVENTION: Patients received 50 mg Captopril or placebo twice a day. MEASUREMENTS: Ambulatory blood pressure, renal function, extracellular volume, and echocardiographic indices of cardiac function and dimensions were assessed annually. Clinic blood pressure and urinary albumin excretion were measured every 3 months. RESULTS: Twenty-four hour mean arterial blood pressure was unchanged in the Captopril group (mean +/- SD) (baseline 93 +/- 4 and follow up 91 +/- 8 mmHg) and in the placebo group (96 +/- 7 and 97 +/- 10 mmHg, NS). Night/day ratio of blood pressure was unaffected. Glomerular filtration rate was unchanged and renal plasma flow increased in the Captopril (557 +/- 97 and 600 +/- 112 ml min-1) versus the placebo group (574 +/- 85 and 535 ml min-1, p = 0.05). Filtration fraction was reduced in the Captopril versus the placebo group (p < 0.05). Extracellular volume and echocardiographically derived parameters were unaffected. The relative change in day time mean arterial blood pressure in the Captopril group correlated with changes in urinary albumin excretion (Spearmans r = 0.85, p < 0.05) unlike clinic mean arterial blood pressure (r = 0.33, p = 0.35). CONCLUSION: Diurnal rhythm of blood pressure was unaffected by long term administration of Captopril. Renal plasma flow was increased and filtration fraction reduced. A significant association between changes in urinary albumin excretion and blood pressure after Captopril was revealed only by the implementation of ambulatory blood pressure measurements.

Adult↗