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Biomedical subjects

H Hohage

Publications and source records attributed to H Hohage.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effects of cyclosporin A and FK 506 on lipid metabolism and fibrinogen in kidney transplant recipients.

After allogenic transplantations a dramatic increase in the development of arteriosclerotic plaques can be observed, which might be due to metabolic alterations, influenced by changes of the transplant organ or immunosuppression. In this study the effects of FK 506 in kidney transplant patients on cardiovascular risk factors were compared to cyclosporin A (CsA) immunosuppression. Both groups showed no statistical differences in number, kidney function, age, body weight, sex distribution, steroid dosage and follow-up time after transplantation. Total cholesterol was similar in FK 506-treated patients (231 +/- 22 vs. 278 +/- 52 mg/dl) as compared with patients with CsA immunosuppression. Furthermore, there were no differences in triglycerides (220 +/- 72 vs. 210 +/- 67 mg/dl), HDL-cholesterol (67 +/- 14 vs. 52 +/- 18 mg/dl) and fasting glucose (112 +/- 36 vs. 116 +/- 17 mg/dl). However, the concentration of LDL-cholesterol (114 +/- 21 vs. 167 +/- 37 mg/dl), the independent risk factor Lp(a) (11 +/- 9 vs. 27 +/- 8 mg/dl) and fibrinogen (216 +/- 71 vs. 297 +/- 47) was lower in FK 506-treated patients. Our results indicate that FK 506 immunosuppression offers some advantages in cardiovascular risk factors.

Adult↗
PubMed1997

Renal and blood pressure effects of moxonidine and clonidine in spontaneously hypertensive rats.

Recently we could demonstrate that the imidazoline receptor agonist moxonidine exerts specific renal effects in Sprague Dawley rats [Hohage et al. 1997]. Interestingly, the effects of this compound are attenuated in one kidney-one clip hypertensive rats [Li et al. 1994]. In this study, we therefore investigated the effects of moxonidine as compared to clonidine in genetically determined spontaneously hypertensive rats. Moxonidine in a concentration of 0.5 mg/kg b.w.i.v. induced a significant and long-lasting increase of both urine flow from 11.9 +/- 2.1 microliters/min x 100 g b.w. to 50.3 +/- 12.5 microliters/min x 100 g b.w. and of Na(+)-excretion from 2.2 +/- 0.5 mumol/min x 100 g b.w. to 8.4 +/- 1.9 mumol/min x 100 g b.w. In contrast to moxonidine, the effects of clonidine (0.5 mg/kg b.w.i.v.) on urine flow and Na(+)-excretion were negligible. The antagonists idazoxan, effaroxan and rauwolscine abolished the effects of moxonidine on urine flow and Na(+)-excretion, whereas 4-aminopyridine, phenformine and 1,2,3,4-tetrahydro-9-aminoacridine, which have been described to interact with imidazoline binding sites, had no effect. Addition of the antagonists idazoxan, effaroxan and rauwolscine attenuated the initial blood pressure increase immediately after intravenous application, whereas 4-aminopyridine, phenformine and 1,2,3,4-tetrahydro-9-aminoacridine had no influence on this side-effect. Our results provide further evidence that imidazoline receptor agonists such as moxonidine exhibit renal effects, different from the modulation in urine flow and Na(+)-excretion following renal alpha 2 adrenoceptor stimulation. An upregulation of imidazoline receptors in hypertension may contribute to the effects observed.

4-Aminopyridine↗
PubMed1996

[Polyneuropathy, diarrhea].

A 44-year-old patient with 24 kg reduction of body weight within three years due to recurrent diarrhea was admitted to the hospital. Physical findings of the patient were not remarkable, except for hypesthesia and hypalgesia of the front of the tibia and of the lower legs. Laboratory as well as endoscopic and functional examinations of the gastrointestinal tract did not reveal any remarkable finding. Infectious origins of the disease were excluded. A histological examination of a rectum specimen yielded amyloid deposits in the submucosa of the rectum. In the family history of the patient, relatives with liver and gastrointestinal diseases due to amyloidosis were detected. Amyloid deposits and the positive family history of the patient led to the diagnosis of a gastrointestinal manifestation of familial amyloidosis.

Adult↗
PubMed1996

[Acute tetraplegia, diabetes mellitus (clin conference)].

A 48-year-old patient with massive obesity developed a dramatic increase of serum glucose and sodium concentration as first symptom of a so far unknown diabetes mellitus. A treatment with intravenous insulin infusion and administration of free water was initiated. Two weeks after this event he became comatose, developed dysphagia, a speech disorder and ocular bobbing; finally, he showed the picture of a complete tetraparesis. Computertomographic findings of the brain were unremarkable. Two weeks later physical findings of the patient showed a significant improvement. Dysphagia, speech disorder and even the tetraparesis disappeared. Computertomography of the brain now yielded a hypodense area within the pons. The symptoms can be understood as signs of central pontine myelinolysis, which may be due to hypo-osmolarity or fast equilibration of a hypo-osmolarity. The history of this patient is a rare example of a central pontine myelinolysis with spontaneous remission.

Diabetes Complications↗
PubMed1996

Effects of diadenosine polyphosphates on renal function and blood pressure in anesthetized Wistar rats.

In this study, the effects of diadenosine polyphosphates on kidney function were examined. Intravenous application of diadenosine hexaphosphate (AP6A) led to a significant threefold increase in both urine flow (from 2.45 +/- 0.2 to 13.8 +/- 0.74 microL/min per 100 g body wt (P < 0.05)) and Na+ excretion (from 0.41 +/- 0.12 to 1.52 +/- 0.28 mumol/min per 100 g body wt at a dose of 1.0 mg/kg body wt). In contrast, diadenosine triphosphate dose-dependently reduced urine flow (from 3.74 +/- 0.3 to 2.57 +/- 0.1 microL/min per 100 g body wt (P < 0.05)) and Na+ excretion (from 0.45 +/- 0.1 to 0.13 +/- 0.1 mumol/min per 100 g body wt at a dose of 1.0 mg/kg body wt). ATP and the P2y purinoceptor agonist gamma-S-ATP did not significantly modulate urine flow and Na+ excretion. alpha, beta-methylene-ATP, a P2x purinoceptor agonist, significantly increased urine flow from 1.74 +/- 0.5 to 4.07 +/- 1.51 microL/min per 100 g body wt, whereas Na+ excretion was unaffected. The effects were independent of alterations in GFR. Pretreatment with indomethacin (2.0 mg/kg body wt iv) completely abolished the effects of AP6A on urine flow and Na+ excretion. Similarly, pretreatment with the endothelin antagonist bosentan abolished the effects of AP6A on both urine flow and Na+ excretion, whereas suramin had no effects on the AP6A-induced increase in urine flow. In conclusion, diadenosine polyphosphates exert specific actions on urine flow and Na+ excretion that are different from the effects of ATP. AP6A may partially influence renal function by stimulating prostaglandin and endothelin release.

Anesthesia↗
PubMed1996

Influence of cyclosporine A and FK506 on 24 h blood pressure monitoring in kidney transplant recipients.

Cyclosporine A (CsA) seems to exert direct effects on blood pressure and diurnal blood pressure alterations. After kidney transplant about 60% of the recipients are suffering from such alterations. In the present study, blood pressure profiles of 15 FK506-treated kidney transplant patients were compared to recipients with CsA immunosuppression. Both groups showed no statistical differences in number, kidney function, age, body weight, sex distribution and time after transplantation. Mean arterial blood pressure in FK506-treated patients at daytime was 105 +/- 2.5 mmHg, at night 109 +/- 3.0 mmHg. Systolic blood pressure difference was 2.3 mmHg, diastolic day/night blood pressure difference 0.6 mmHg, and the difference of the heart frequency 6.8 beats/min. Cyclosporin A-treated patients showed a mean arterial blood pressure during the day of 107 + 2.6 mmHg, at night-time a mean arterial blood pressure of 107 + 3.4 mmHg was measured. The diurnal blood pressure alterations of systolic blood pressure were 0.9 mmHg, diastolic blood pressure difference 3.5 mmHg respectively, the heart frequency showed a difference of 4.4 beats/min. Both, FK506-treated patients and patients with CsA immunosuppression exhibit reduced diurnal blood pressure alterations. Furthermore, mean arterial pressure in both, FK506 and CsA-treated patients was elevated and showed no statistical differences between the groups. In FK506-treated patients, however, antihypertensive therapy was less intensive. Concerning arterial blood pressure and diurnal blood pressure alterations, FK506 offers no advantages as compared to cyclosporine A. The reduced usage of antihypertensive drugs, however, may give evidence for lower hypertensive properties of FK506 as compared to CsA.

Adult↗
PubMed1996

The basolateral organic cation transport system of rabbit kidney proximal tubules. Influence of anorganic anions.

The influence of different extracellular chloride concentrations of chloride channel blockers and of inorganic anions on renal basolateral organic cation transport was examined on isolated nonperfused S2 segments of superficial proximal tubules of rabbit kidney. Tritium-labeled tetraethylammonium (TEA) with a high specific activity of 13.5 Ci/mmol was used as a model substrate of the organic cation transport system. With the experimental conditions chosen, the TEA accumulation in the cells reflects the TEA transport across the basolateral membrane. A maximum TEA cell to a bath ratio of 711 was observed at a TEA bath concentration of 1.4 x 10(-7) M. Increasing TEA bath concentrations lead to a nonlinear reduction of the TEA cell to the bath ratio. Superficial proximal S2 segments showed a significantly higher accumulation of TEA as compared to the S1 or S3 segments. No significant differences could be found between superficial and juxtamedullary S2 segments. Chloride ions significantly modulated the basolateral cation transport system in the S2 segments. In a chloride-free medium, virtually no TEA transport could be detected. Furthermore, iso-osmotic replacement of chloride in the incubation medium by iodide, sulfate or nitrate significantly reduced tubular TEA accumulation, whereas bromide was without effect. Chloride channel blockers had no effect on TEA transport, and TEA did not significantly influence 36chloride uptake of the S2 segments. Our study demonstrates extensive concentrative TEA accumulation in S2 proximal segments at the low TEA bath concentrations. Extracellular chloride may modulate the tubular TEA uptake, probably indirectly via the basolateral chloride/bicarbonate exchanger. A chloride/TEA cotransport seems to be excluded.

Animals↗
PubMed1995

[Frequent airway infections].

A 44-year-old patient experienced increasing shortness of breath and cough with yellow expectoration. Physical findings of the patient were not remarkable, whereas x-ray chest examination revealed cicatricial changes of the lower fields of the right lung. Laboratory findings showed a significant reduction of plasma gamma-globulin levels due to a global deficiency of all immunoglobulins. An infectious origin of the immunoglobulin deficiency was not detected. After exclusion of other acquired etiologic conditions, the diagnosis of a variable immunodeficiency syndrome was established. After antibiotic treatment with gyrase-inhibitors, an immunoglobulin-substitution program was initiated. Immediately after the start of an immunoglobulin infusion, the patient developed an allergic reaction. Pretreatment with antihistamine drugs eliminated allergic symptoms. Following immunoglobulin treatment, incidence and severity of infectious diseases were significantly reduced.

Adult↗
PubMed1994

Studies of the vessel wall properties in hemodialysis patients.

Compliance is an important property of the arterial system and abnormalities in compliance can greatly affect cardiovascular function. The elastic properties of the common carotid artery were therefore studied in 24 normotensive hemodialysis patients and 24 healthy normotensives using a noninvasive technique. The hemodialysis patients and the control subjects were matched for blood pressure. Arterial distension was measured by Doppler analysis of the vessel wall movements and blood pressure was recorded by finger-phlethysmography (Finapres). The vessel wall distensibility (DC: 2.49 +/- 0.23 10(-3)/mm Hg; mean +/- SEM) was significantly reduced and the end diastolic diameter (d: 7.3 +/- 0.3 mm) was significantly increased in younger hemodialysis patients (36.3 +/- 2.0 years) when compared with age-related controls (DC: 3.44 +/- 0.24 10(-3)/mm Hg; d: 6.3 +/- 0.3 mm; mean +/- SEM). In older hemodialysis patients (60.2 +/- 2.3 years), there was no significant difference in vessel wall distensibility (DC: 1.55 +/- 0.15 10(-3)/mm Hg) and vessel diameter (d: 7.8 +/- 0.3 mm) as compared with age-matched controls (DC: 1.77 +/- 0.14 10(-3)/mm Hg; d: 7.2 +/- 0.3 mm). The results show that vessel wall distensibility of the common carotid artery is decreased in younger hemodialysis patients as compared with age-matched healthy subjects. The volume expanded state in hemodialysis patients cannot account for the decreased arterial distensibility, since volume depletion by hemodialysis was not associated with a significant change of arterial distensibility (DC 2.14 +/- 0.44 10(-3)/mm Hg before, DC 2.26 +/- 0.45 10(-3)/mm Hg after ultrafiltration, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Cost/benefit relations: therapy of hypertension].

Antihypertensive therapy improves the long-term prognosis of patients with mild to moderate essential hypertension and is able to prevent complications. This is also true for the elderly patient with hypertension. A considerable percentage of patients with mild essential hypertension can be adequately treated without drugs. If drug treatment is required, diuretics, beta-blockers, calcium antagonists, and ACE-inhibitors are the agents of first choice. For the individual patient, the appropriate drug should be chosen on the basis of efficacy, lack of side-effects, and depending upon additional diseases, such as cardiac failure, coronary heart disease and renal failure. Only if these selection criteria are fulfilled should differences in prices of the various groups of antihypertensive agents be considered.

Aged↗
PubMed1994

Regulation by protein kinase C of the contraluminal transport system for organic cations in rabbit kidney S2 proximal tubules.

In the present study the effects of structurally different stimulators of protein kinase C (PKC) (phorbolesters and oleylacetylglycerol) as well as of staurosporine, a specific inhibitor of PKC activity, on the uptake of tetraethylammonium (TEA), a maker of the renal cation transport system, was investigated on isolated S2 segments of rabbit kidney proximal tubules. Because the tubules were not perfused, and hence were collapsed, the cellular uptake of TEA reflects transport across the contraluminal membrane. The results show that the phorbolester phorbol 12-myristate 13-acetate induced a dose- and time-dependent stimulatory effect on tubular TEA uptake. The presence of extracellular chloride ions was a prerequisite for the action of phorbol 12-myristate 13-acetate on the cation transporter. The phorbolester 4 alpha-phorbol 12, 13-didecanoate also stimulated TEA uptake, but to a much lower degree than phorbol 12-myristate 13-acetate. The effects of the phorbolesters could be mimicked by oleylacetylglycerol, a membrane-permeant analog of the physiological PKC activator diacylglycerol. Staurosporine inhibited TEA transport with basal conditions, and after stimulation with the phorbolesters. The data provide the first evidence that PKC is involved in the regulation of the renal contraluminal transport system for organic cations.

Animals↗
PubMed1994

The renal basolateral transport system for organic anions: properties of the regulation mechanism.

The aim of the present study was to investigate whether the activity of the renal basolateral transport system for organic anions is modulated by protein kinase C (PKC). The studies were performed on isolated nonperfused S2 segments of proximal tubules, microdissected from rabbit kidneys without the use of enzymatic agents. Several PKC-activating substances and staurosporine, a PKC inhibitor, were added to the incubation solution containing 3H-PAH at 6.5 x 10(-7) M as a marker substance for the basolateral anion transporter. The phorbol ester phorbol 12-myristate 13-acetate showed dose-dependent effects on the tubular PAH uptake, inducing a 2-fold increase in the PAH transport rate compared with control at a concentration of 10(-7) M. Oleyl-2-acetylglycerol, a membrane permeant analog of the physiological PKC activator diacylglycerol, had similar effects, but the maximum stimulating concentration was 10(-5) M. The shift to higher concentrations might be due to an intracellular metabolization of oleyl-2-acetylglycerol. In addition, myoinositol, a precursor of the PKC-activating pathway, induced a 2-fold increase in PAH accumulation at a concentration of 10(-5) M. These effects were abolished by the administration of staurosporine at low concentrations (10(-9) and 10(-8) M). Staurosporine on its own diminished the PAH uptake in a concentration-dependent manner at bath concentrations ranging from 10(-7) to 10(-5) M. We conclude that the PKC system may be an important modulator of the basolateral PAH transport in renal S2 proximal tubules.

Alkaloids↗
PubMed1993

Glucose-6-phosphate: a key compound in glycogenosis I and favism leading to hyper- or hypolipidaemia.

The glycogen storage disorders (GSD)-I, -III, -VI and -VIII are associated with hypertriglyceridaemia or mixed hyperlipidaemia which poses the question whether these patients have an increased risk for atherosclerosis. The atherogenicity of triglycerides has remained controversial, while increased plasma cholesterol levels are generally accepted as a significant risk factor for coronary heart disease. However, clinical data show that one has to differentiate between metabolic conditions where triglycerides are atherogenic and those which are not significantly related to early onset of atherosclerosis but may cause other disorders such as pancreatitis. Among the disorders of carbohydrate metabolism patients with diabetes mellitus frequently have enhanced plasma triglycerides associated with a higher risk for coronary heart disease, while patients with certain types of glycogen storage disease have high triglyceride levels but do not seem to have an enhanced risk for atherosclerosis. Here we have compared the biochemical abnormalities and the atherogenic risk of three different disorders of glucose metabolism including GSD-I (glucose-6-phosphatase deficiency), favism (glucose-6-phosphate dehydrogenase deficiency), and diabetes mellitus which are related to either hyper- or hypolipidaemia. The available data indicate that glucose-6-phosphate (Glc-6-P) is a central molecule in cellular glucose metabolism which critically influences pentose phosphate cycle activity and, via NADPH2-generation, regulates glutathione peroxidase activity for radical detoxification and also cholesterol and triglyceride synthesis. Radical detoxification is a major protective factor for cell membrane integrity and together with an appropriate renewal of membrane lipids may protect against the development of atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1993

[Stroke, epilepsy and abdominal pain as leading symptoms in a case of mitochondrial encephalomyopathy].

A 17-year old girl presented with recurrent seizures, strokes, fatigue, vomiting, cerebellar ataxia, dementia and hypertrichosis. Further examinations showed jerking left-sided arm reflexes, partial internal deafness and myopathy. CT and MR of the skull revealed radiolucencies within the cerebral matter of the cortex and the medulla. Laboratory tests showed increased levels of lactate and pyruvate in serum and cerebro-spinal fluid. Microscopic examination of muscular tissue showed "ragged red fibers". Electron microscopy yielded crystal inclusions in mitochondria. The symptoms represented the complete picture of the so-called MELAS/MERRF-complex, which can be easily misdiagnosed as strokes and seizures of unknown cause.

Abdominal Pain↗
PubMed1993

[Anaphylactic reaction in streptokinase therapy].

Streptokinase is used worldwide as thrombolytic agent. Indications are deep vein thrombosis, arterial thrombosis and embolism, arteriovenous cannula occlusions, acute coronary artery thrombosis, and acute renal vein thrombosis. The major drawback in comparison with other thrombolytic drugs is its antigenicity. Allergic reactions have been reported but the underlying mechanisms have not yet been fully elucidated. A 58 year-old man with acute myocardial infarction developed an anaphylactic reaction immediately after commencement of streptokinase infusion, although immunological laboratory findings were not affected. The patient had no history of prior exposure to streptokinase, infections with streptococci, or chronic allergic reactions. 2 months after streptokinase therapy increased plasma levels were detected of specific IgG antibodies to streptokinase. The levels of specific IgE antibodies to streptokinase and other anti-streptococcal antibodies were within the normal range. A prick test performed 4 months later with 100 I.U. streptokinase was unremarkable. The problems of such allergic reactions are discussed on the basis of this case report and a review of the literature.

Anaphylaxis↗
PubMedDate not supplied

Effects of inorganic divalent cations on the renal basolateral transport system for organic anions.

Recent work demonstrated that the heavy metal ion Cd2+ increases the transport of p-aminohippuric acid (PAH) across the basolateral membrane of microdissected non-perfused rabbit kidney S2 proximal tubule segments. Usually, such ions induce damage of various renal transport systems, therefore the effects of divalent metal ions Zn2+, Co2+ and Ni2+ on this transporter were investigated. Addition of Ni2+ or Zn2+ to the bathing solution leads to a significant reduction of basolateral PAH transport, with IC50 values of 2 x 10(-5) and 10(-6) M, respectively, whereas Co2+ failed to inhibit PAH accumulation. Simultaneous incubation with thrombin (10(-9)M), which is known to increase [Ca2+]i, abolished the effects of the divalent ions. Our results indicate that Ni2+ and Zn2+ reduce cellular PAH uptake. Because Ni2+ and Zn2+ are calcium channel blockers, these effects are probably due to a reduction of [Ca2+]i by an interaction of these metals with binding sites in the calcium channel, whereas Co2+ does not affect these binding sites. This finding is supported by the fact that thrombin abolished the cation effects.

Animals↗