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Biomedical subjects

T Philipp

Publications and source records attributed to T Philipp.

At least 163 records · Page 9Linked to original sources
PubMed1994

Ontogenesis of sympathetic responsiveness in spontaneously hypertensive rats. II. Renal G proteins in male and female rats.

Previously we have reported an increased renal alpha 1- and beta-adrenergic receptor expression in male spontaneously hypertensive rats that occurred ontogenetically in parallel with blood pressure elevation. However, increased receptor numbers were not accompanied by enhanced stimulation of inositol phosphate and cyclic AMP formation, respectively, indicating relative desensitization. We have now quantified alpha-subunits of the G proteins Gs (Gs short and Gs long), G(i), and Gq by immunoblotting and pertussis toxin-catalyzed ADP-ribosylation in renal membranes from 3-, 6-, 8-, and 28-week-old normotensive and spontaneously hypertensive male Wistar-Kyoto rats; additionally, 28-week-old female normotensive and spontaneously hypertensive rats were studied. During ontogenesis of male normotensive rats, Gs short increased, Gs long remained unchanged, and G(i) alpha and Gq alpha decreased. In adult normotensive rats no sex differences were detected for Gs short, Gs long, and G(i) alpha. When male rats from the normotensive and spontaneously hypertensive strains were compared, all G protein alpha-subunits were similar in the prehypertensive phase (3 weeks). In established hypertension (28 weeks), Gs long and Gq alpha were reduced, whereas Gs short and G(i) alpha remained unchanged. Gs long was also reduced during the development of hypertension (6 and 8 weeks), whereas Gs short and G(i) alpha were not consistently altered in this phase. The reduction in Gs long seen in male adult hypertensive rats was not detectable in female hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Interstitial nephritis in typhus].

A 58-year-old man developed continuous fever of around 40 degrees C and a macular rash on the trunk and limbs one week after an eight-day visit to the island of Rhodos. Typhus was diagnosed on the basis of the clinical findings, the characteristic rash and a rise in antibody titre against Rickettsia prowazekii and mooseri (1:1280). The fever subsided and the patient's general state markedly improved within three days of starting antibiotic treatment with doxycycline. Five days after hospital admission renal function deteriorated, serum creatinine rising from 1.7 to maximally 8.7 mg/dl. Renal biopsy on the eighth day of illness revealed, in concordance with the diagnosis of a rickettsial infection, acute granulomatous interstitial nephritis. Doxycycline administration was continued for a total of 18 days and renal function improved. Two weeks after discharge serum creatinine had fallen to 1.8 mg/dl and to 1.2 mg/dl after 6 months. The antibody titre against Rickettsia prowazekii had fallen to 1:20 about 12 weeks after discharge. Early antibiotic treatment of typhus is of importance to avoid irreversible renal damage.

Antibodies, Bacterial↗
PubMed1993

The effect of extracorporeal high blood flow rate on left ventricular function during hemodialysis--an echocardiographic study.

The effect of increased extracorporeal blood flow rate on left ventricular (LV) function has been studied during volume-controlled bicarbonate hemodialysis. Ten stable patients on chronic hemodialysis, with a mean age of 28 years (range 19-38) were studied using two-dimensional and Doppler echocardiography. The mean time on hemodialysis was 32 months (range 3-60). All patients were investigated during three dialysis sessions on the first day of the week for 3 consecutive weeks. The blood flow rate was chosen randomly as 250, 350, or 450 cc/min. Apart from the time of hemodialysis and blood flow rate, other parameters of the hemodialysis were kept stable during all three sessions. Echocardiographic studies were done before, at mid dialysis, and during the last 15 min of each dialysis session. The following parameters were evaluated: heart rate, mean blood pressure, shortening fraction, ejection fraction, cardiac output, and pre-ejection period/LV ejection time ratio. The changes of the measured cardiac parameters at the beginning, middle and end of each session were not significantly different. Furthermore, the differences in changes between the three different sessions were comparable. Our results indicate that an increase in dialysis blood flow rate up to 450 cc/min does not have an adverse effect on the left ventricle in patients on maintenance hemodialysis and with stable cardiovascular function.

Adult↗
PubMed1993

Alpha 1A and alpha 1B-adrenoceptors enhance inositol phosphate generation in rat renal cortex.

We have studied the role of alpha 1A- and alpha 1B-adrenoceptors in noradrenaline- and methoxamine-stimulated inositol phosphate accumulation in rat renal cortical slices. [3H]Prazosin binding studies with and without inactivation of alpha 1B-adrenoceptors by chloroethylclonidine treatment suggested that noradrenaline lacks relevant selectivity for alpha 1-adrenoceptor subtypes. Both agonists stimulated [3H]inositol phosphate accumulation with similar maximal effects. The alpha 1A-selective antagonists 5-methyl-urapidil and (+)-niguldipine inhibited inositol phosphate formation by both agonists with shallow biphasic curves but the high affinity component was only 15%-31% and 38%-41%, respectively. The irreversible alpha 1B-selective antagonist chloroethylclonidine inhibited inositol phosphate generation by both agonists by 54%-57%. In contrast to our previous data in rat cerebral cortical slices, we conclude that in rat renal cortex both alpha 1A- and alpha 1B-adrenoceptors are involved in noradrenaline- and methoxamine-stimulated inositol phosphate generation.

Adrenergic alpha-Antagonists↗
PubMed1993

Different effects of eicosapentaenoic acid and olive oil on blood pressure, intracellular free platelet calcium, and plasma lipids in patients with essential hypertension.

In a randomized, double-blind, crossover study our specific aim was to examine the effects of a dietary fish oil or olive oil supplementation on blood pressure, intracellular free platelet calcium, plasma lipoproteins, and circulating vasoactive substances such as norepinephrine, epinephrine, and renin in patients with essential hypertension. Ten hypertensive patients (WHO classes I, II) were randomly assigned to receive 9 g fish oil or 9 g olive oil daily for 6 weeks after a 4-week baseline period. The 6-week treatment periods were separated by a 4-week wash-out. During treatment with fish oil diastolic blood pressure decreased from 103 +/- 1 to 98 +/- 2 mmHg (P < 0.05) but did not change significantly during olive oil intake. Systolic blood pressure was not affected by either treatment. Intracellular free platelet calcium decreased in patients receiving fish oil (from 102 +/- 8 nM to 86 +/- 6 nM, P < 0.05) but was not significantly altered by olive oil treatment. In contrast, the dose-response curve for thrombin-induced intracellular free platelet calcium was not altered by the fish oil enriched diet. Plasma triglycerides decreased by approximately 40% in the fish oil group while low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total cholesterol were not altered. Renin activity, norepinephrine, and epinephrine in plasma were not influenced by fish oil supplementation. We conclude that a moderate increase in dietary fish oil reduces diastolic blood pressure, intracellular free platelet calcium, and plasma triglycerides in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Acute liver necrosis in the HELLP syndrome: successful outcome after orthotopic liver transplantation. A case report.

We discuss the case of a 30-year-old primipara woman who developed a liver rupture as a complication of the HELLP syndrome. A liver necrosis and bleeding made a hepatectomy necessary. A portocaval shunt was able to maintain the patient until she underwent urgent liver transplantation. In an excellent state of recovery, the woman and her baby were discharged from the hospital 66 days after having been admitted.

Adult↗
PubMed1993

Ontogenesis of sympathetic responsiveness in spontaneously hypertensive rats. I. Renal alpha 1-, alpha 2-, and beta-adrenergic receptors and their signaling.

We studied the ontogenetic development of renal alpha 1-, alpha 2-, and beta-adrenergic receptors and their coupling to inositol phosphate and cyclic AMP formation in spontaneously hypertensive and normotensive Wistar-Kyoto rats. alpha 1-, alpha 2-, and beta-Adrenergic receptor number was significantly increased in hypertensive compared with normotensive rats, but the increase did not precede blood pressure elevation. Despite increased alpha 1-adrenergic receptors, basal and norepinephrine-stimulated inositol phosphate formation remained unchanged in all age groups. Rat kidney contains alpha 1A- and alpha 1B-adrenergic receptors coupling to inositol phosphate formation by different mechanisms, but the relative contribution of alpha 1A- and alpha 1B-adrenergic receptors to norepinephrine-stimulated inositol phosphate formation was similar in normotensive and hypertensive rats. Despite increased beta-adrenergic receptors, basal, isoproterenol-, and forskolin-stimulated cyclic AMP accumulation was similar in normotensive and hypertensive rats. We conclude that the number but not the functional responsiveness of renal adrenergic receptors increases in spontaneously hypertensive rats. Thus, the additional receptors are unlikely to contribute to the pathophysiology of elevated blood pressure in this model.

Animals↗
PubMed1992

Alpha- and beta-adrenoceptors in hypertension: molecular biology and pharmacological studies.

Recent years have witnessed astonishing progress in our understanding of the molecular basis of adrenoceptor structure, function and regulation and revealed an unexpected heterogeneity of adrenoceptors demonstrating the existence of at least 11 subtypes. This paper discusses the implications of these advances on studies regarding a specific role of adrenoceptors in the development of genetic hypertension. The available data indicate that among the alpha-adrenoceptor subtypes the alpha 2A-adrenoceptor is the most likely candidate for an alteration specifically linked to genetic hypertension in the animal model of the spontaneously hypertensive rat and possibly in some patients. Alterations of other alpha-adrenoceptor subtypes may be specific for some forms of genetic hypertension but are unlikely to play an important role for blood pressure regulation. Most beta-adrenoceptor alterations appear to occur secondary to blood pressure elevation independently of whether hypertension has occurred on a genetic basis or not. Moreover, the mechanisms regulating alpha- and beta-adrenoceptor responsiveness upon prolonged agonist exposure may be altered in hypertension and thereby contribute to the pathophysiology of this disease.

Adrenergic alpha-Antagonists↗
PubMed1992

On the role of renal alpha-adrenergic receptors in spontaneously hypertensive rats.

We tested the hypothesis that a genetically determined increase in renal alpha-adrenergic receptor density might be a pathophysiologically important factor in the spontaneously hypertensive rat model of genetic hypertension. In a first study, we compared renal alpha 1 and alpha 2-adrenergic receptor density with systolic blood pressure in 45 rats of an F2 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids but were unable to detect significant cosegregation between either receptor density or blood pressure. In a second study, we determined renal alpha 1- and alpha 2-adrenergic receptor density in Wistar-Kyoto and spontaneously hypertensive rat kidneys that were transplanted into an F1 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids. Although Wistar-Kyoto kidneys lowered blood pressure in these animals and spontaneously hypertensive rat kidneys increased blood pressure, renal alpha-adrenergic receptor densities were similar in membranes from both types of kidneys. Since rat kidney coexpresses alpha 1A- and alpha 1B-adrenergic receptors, we also investigated whether differential regulation of these two subtypes might conceal ongoing alterations. The alpha 1A/alpha 1B-adrenergic receptor ratio, however, was similar in Wistar-Kyoto rats, spontaneously hypertensive rats, and F1 rats transplanted with a kidney from either strain. Taken together these data do not support the hypothesis that genetically determined alterations of renal alpha-adrenergic receptor numbers play an important role in the development of elevated blood pressure in the spontaneously hypertensive rat.

Animals↗
PubMed1992

Lack of oral kallikrein in lowering systemic blood pressure in primary hypertension.

Primary hypertension is associated with a lack in renal kallikrein activity which might be one of the reasons for the blood pressure elevation. Some smaller and partially uncontrolled studies suggested that an oral substitution of glandular kallikrein lowers blood pressure by a kinin-mediated vasodilation and increased natriuresis. To test this hypothesis we treated in two studies over 100 patients with untreated mild to moderate primary hypertension (WHO I-II) for 5 resp. 12 weeks in a double blind randomized and placebo controlled manner with 1800 U glandular kallikrein orally. Blood pressure measurements were performed according to the two study designs after 3 and 5 resp. 8 and 12 weeks of treatment sphymomanometrically in the day time course. No significant changes in blood pressure by kallikrein treatment could be observed at any time. Neither renal kallikrein excretion, renin and ACE-activity nor blood glucose concentration in diabetics or non-diabetics was changed. Thus, we could undoubtedly demonstrate that oral applied glandular kallikrein has no effect on primary hypertension.

Administration, Oral↗
PubMed1991

[Effect of erythropoietin therapy on alpha receptor density in chronic dialysis patients].

The effect of a six months therapy with human recombinant erythropoietin (rHu-EPO) on blood pressure and on several parameters of sympathetic nervous activity was studied in chronic haemodialysis patients in a controlled and randomized trial in order to gain further insight into the mechanism of rHu-EPO-induced blood pressure elevation. Treatment was started at a dose of 3 X 80 IE/kg/week in eleven patients aiming to increase the initial hemoglobin concentration (7.0 +/- 0.3 [SEM] g%) to 10.0 g% by dose adjustments, while another untreated eleven patients served as a control group. Diastolic arterial pressure measured before and after haemodialysis increased on rHu-EPO treatment by 7 and 8 mm Hg respectively (p less than 0.05). Plasma noradrenaline concentration was increased (p less than 0.05) after the six months treatment period in the presence of unchanged dry weights. Conversely platelet alpha 2-adrenoceptor density (3H-yohimbine binding) and the fraction of high affinity binding sites for alpha 2-agonists (3H-UK 14.304) decreased (p less than 0.01) along with a decrease in reactivity to exogenous noradrenaline (p less than 0.05). None of these parameters changed in the control group compared to pretreatment values. The results obtained demonstrate that increased plasma noradrenaline concentrations may participate in rHu-EPO induced blood pressure increases. The decrease in platelet alpha 2-adrenoceptor densities and the decrease in noradrenaline reactivity in the presence of increased plasma noradrenaline concentrations suggest an intact regulation of alpha 2-adrenoceptors in chronic haemodialysis patients on chronic rHu-EPO therapy.

Blood Platelets↗
PubMed1991

Does treatment with beta-adrenoceptor antagonists in vivo alter human adenylate cyclase responsiveness in vitro?

1. Treatment with beta-adrenoceptor antagonists in vivo can alter adenylate cyclase responsiveness in the human heart. We have determined the effects of treatment with four different beta-adrenoceptor antagonists in vivo on the responsiveness of lymphocyte and platelet adenylate cyclase in vitro in healthy volunteers. 2. Propranolol (non-selective, 4 x 40 mg day), bisoprolol (beta 1-selective, 1 x 10 mg day), and ICI 118.551 (beta 2-selective, 3 x 25 mg day) were tested as drugs without and pindolol (non-selective, 2 x 5 mg day) as a drug with intrinsic sympathomimetic activity. Adenylate cyclase stimulation by GTP, prostaglandin E1 and forskolin was determined before, after a 7 day treatment period and 7 days after drug withdrawal. 3. Neither treatment with or withdrawal of any of the beta-adrenoceptor antagonists altered adenylate cyclase responsiveness. 4. We conclude that adenylate cyclase responsiveness in circulating blood cells underlies different regulatory mechanisms than that in solid tissues such as the human heart. Our data suggest that circulating blood cells do not always reflect alterations in solid tissues.

Adenylyl Cyclases↗
PubMed1991

Influence of the calcium antagonist nitrendipine on the hepatotoxic effect of cyclosporine A.

Calcium antagonists have a protective effect on different forms of nephrotoxicity due to cyclosporine A (CsA). The objective of the present study was to examine the influence of a calcium antagonist on the liver function in CsA-treated patients after kidney transplants. Different quantitative liver function tests were performed in six patients before and 3 months after administration of the calcium antagonist nitrendipine. Indocyanine green clearance (ICG-Cl) as a marker for hepatic blood flow and excretion showed a significant increase under nitrendipine. In addition, there was an improvement of the galactose elimination capacity. Although nitrendipine and lidocaine are both metabolized by the cytochrome P system, there was no reduction in lidocaine clearance. These results suggest an improvement of liver function under nitrendipine. Whether these findings alone are the expression of an improved liver blood flow or whether there is an additional hepatoprotective characteristic of the calcium antagonist nitrendipine cannot be determined.

Cyclosporine↗