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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 66 (1988), S. 924-927 
    ISSN: 1432-1440
    Keywords: Hypertension ; Insulin ; Glucagon ; Skeletal muscle ; Glycogen ; Glucose ; Glycogen synthetase ; Glycogen phosphorylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was performed to investigate as to whether peripheral insulin resistance exists in spontaneously hypertensive rats (SHR). After a 12 h fasting period, SHR had significantly higher serum glucose and higher plasma glucagon values in comparison to normotensive control rats (WKY). There was a tendency for higher serum insulin concentrations as well, but this difference did not reach significance. After oral glucose loading or glucose/insulin administration, serum glucose and insulin levels were also higher in SHR compared to WKY rats. Muscle glycogen and glucose concentrations were identical in fasted SHR and WKY rats. With an oral glucose load or glucose/insulin treatment there was a significant increase in muscle glycogen, whereas glucose values declined in skeletal muscle. Both total (a+b-form) phosphorylase activity as well as the active a-form of the enzyme were similar in skeletal muscle of SHR and WKY rats. Glucose/insulin administration or oral glucose loading induced a considerable reduction of both a+b-form and a-form activities. The decrease in muscle phosphorylase activities was almost identical in both groups of animals. There was also a comparable activity of muscle glycogen synthetase activity in all groups of rats. Despite subtile changes of glucose, glucagon and to a lesser degree insulin levels which would be suggestive of insulin resistance, the data obtained from skeletal muscle argue against peripheral insulin resistance in spontaneously hypertensive rats.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Kidney transplantation ; Cyclosporin ; Azathioprine ; Lipoproteins ; Carbohydrate metabolism ; Hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Various endocrine and metabolic disturbances associated with long standing uremia persist after kidney transplantation or arise from the use of immunosuppressive drugs. Hyperlipidemia for long time being implicated as the cause of corticosteroids is also observed in renal transplant recipients treated with cyclosporin A monotherapy. After conversion from cyclosporin to azathioprine serum cholesterol and triglyceride concentration fall, and elevation of LDL-cholesterol may also be reversed. There is a tendency for higher HDL-cholesterol in azathioprine and prednisolone treated transplant patients. Those patients who are at risk for clinically significant cholesterol elevations can be predicted by their pretransplant lipid levels, specifically the LDL-fraction. Risk-benefit ratio of conversion and of treatment with lipid-lowering drugs, especially with lovastatin, should be carefully examined, also in view of glucose intolerance. Higher incidence of diabetes mellitus requiring insulin therapy in cyclosporin treated transplant recipients has been reported. Cyclosporin may cause toxic effects on pancreatic beta-cells resulting in inhibition of insulin secretion. High doses of cyclosporin induce inhibition of glycogen synthesis in rat liver. Glucose intolerance is reversible after reduction of cyclosporin dose or conversion to azathioprine. Therefore glucose metabolism in kidney transplant recipients treated with cyclosporin should be carefully followed. Immunosuppressive therapy may affect reproductive function, arachidonate metabolism and renin-angiotensin-aldosterone system as well as posttransplant calcium and phophate metabolism. Endocrine and metabolic abnormalities are associated with long standing uremia. After successful kidney transplantation several observations are normalized but further complications arise from the use of immunosuppressive drugs. The present paper reviews various endocrine and metabolic disturbances described following renal transplantation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 65 (1987), S. 581-581 
    ISSN: 1432-1440
    Keywords: Cardiopulmonary bypass ; Granulocyte elastase ; Nifedipine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: 25 Hydroxyvitamin D (25-OH-D) ; 1,25 Dihydroxyvitamin D (1,25-(OH)2-D) ; Nifedipine ; Regular Hemodialysis Therapy (RDT)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Keywords: Acute renal failure ; Chronic uraemia ; Proteases ; Phosphorylase kinase ; Protein catabolism ; Akutes Nierenversagen ; Chronische Urämie ; Proteasen ; Phosphorylase-Kinase ; Eiweißkatabolismus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im ultrafiltrierten Plasma (Molekulargewicht 〈50 000) von vier Patienten mit Polytrauma und akutem posttraumatischen Nierenversagen gelang der Nachweis einer proteolytischen Verdauung der Untereinheiten alpha und gamma von Phosphorylase-Kinase, isoliert aus Skelettmuskulatur von Kaninchen. Es bestand eine Beziehung zwischen der Aktivität der freien proteolytischen Enzyme im ultrafiltrierten Plasma und dem Anstieg der Plasma-Alpha1-Antitrypsin-Werte mit der Schwere und dem ungünstigen Verlauf der Erkrankung. Die Plasma-Alpha2-Macroglobulin-Spiegel waren bei Patienten mit posttraumatischem akuten Nierenversagen deutlich erniedrigt. Im Serum von Patienten mit posttraumatischem akuten Nierenversagen war die Gesamtproteinkonzentration erniedrigt, im Plasmaultrafiltrat signifikant erhöht. Bei zwei Patienten mit akuter hyperurikämischer Nephropathie und drei Patienten mit medikamentös induziertem akuten Nierenversagen, einem Patienten mit akuter Pankreasnekrose und akutem postoperativen Nierenversagen sowie einem Patienten mit chronischer Pankreatitis und Zustand nach Whipple-Operation konnten dagegen im ultrafiltrierten Plasma keine freien proteolytischen Enzyme mit Phosphorylase-Kinase als Substrat entdeckt werden. Die Titration der Plasmaproteaseninhibitoren mit Trypsin ergab eine signifikant verminderte Bindungskapazität bei Patienten mit posttraumatischem akuten Nierenversagen im Vergleich zu Patienten mit chronischer Niereninsuffizienz oder regelmäßiger Hämodialyse und gesunden Kontrollen. Proteolytische Aktivität fanden wir bei chronisch urämischen Dauerdialysepatienten im 100fach ankonzentrierten Diafiltrat (Molekulargewicht 〉10 000). Unsere Daten lassen an eine Beteiligung von Proteasen am Eiweißkatabolismus denken. Während das Blutgerinnungssystem als mögliche Quelle von Proteasen weitgehend ausgeschlossen werden konnte, ist es möglich, daß proteolytische Enzyme nach Polytrauma aus Lysosomen und/oder Makrophagen der Skelettmuskulatur freigesetzt werden.
    Notes: Summary In ultrafiltrated plasma (molecular weight 〈50,000) obtained from four patients with multiple muscular trauma and acute post-traumatic renal failure, it was possible to verify a subcomponential specific digestion of the subunits alpha and gamma of phosphorylase kinase isolated from rabbit skeletal muscle. The activity of free proteolytic enzymes in ultrafiltrated plasma as well as an increase of plasma alpha1-antitrypsin values were correlated with the severity and unfavourable course of the illness. In contrast, the plasma levels of alpha2-macroglobulin were drastically lowered. The mean total protein concentration in the sera of patients with post-traumatic ARF was lowered, whereas the mean ultrafiltrate protein concentration was significantly enhanced. In ultrafiltrated plasma of two patients with hyperuricaemic ARF, three patients with ARF after drug over-dosage, one patient with acute pancreatic necrosis combined with acute renal failure and one patient with chronic pancreatitis, no proteolytic activity could be detected using phosphorylase kinase as substrate. Studies on the trypsin binding capacity of the plasma protease inhibitors revealed a significantly lowered level in patients with post-traumatic acute renal failure as compared to healthy controls, patients with chronic renal insufficiency and patients on regular dialysis treatment. Proteolytic activity was found in ca. 100-fold concentrated diafiltrates (molecular weight 〉10,000) of patients on regular dialysis treatment. Our data suggest a participation of proteases on protein catabolism in hypercatabolic states. Whilst the blood coagulation system can largely be excluded as a source of proteases, it is possible that proteolytic enzymes may be released from muscle lysosomes and/or macrophages after multiple muscular trauma.
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  • 6
    ISSN: 1432-1440
    Keywords: Granulocyte lysosomal factors ; Elastase ; Acute and chronic uremia ; Catabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In uremic intoxication proteolytic activity in plasma and striated muscle is enhanced. To get further insights into the underlying mechanisms the lysosomal factors of polymorphonuclear (PMN) leukocytes and the plasma elastase-α 1-proteinase inhibitor complex were investigated in patients with acute and chronic renal failure. Lysosomal activity was evaluated in peripheral blood smears by the lysis of erythrocytes and plasma (halo formation) around each neutrophil induced by 0.25 M NaCl borate buffer. In about half of the patients with chronic renal insufficiency on dietary treatment lysosomal activity of PMN leukocytes was reduced. The plasma concentration of elastase-α 1-proteinase inhibitor complex was normal in most subjects, but increased in three patients with the highest serum creatinine levels (〉13 mg/dl). In the patients with acute renal failure (ARF) of various origin (postoperatively, septicemia, pancreatitis, or dye-induced) halo formation was either reduced or absent. The plasma elastase-α 1-proteinase inhibitor complex was increased in 5/6 of the patients by a factor of two to four. Also in the patients on regular hemodialysis treatment halo formation of PMN leukocytes was substantially reduced, whereas the plasma levels of elastase-α 1-proteinase inhibitor complex was slightly increased. The finding of reduced lysosomal activity of PMN neutrophils in uremia may be partly due to an enhanced release of neutral proteinases into the circulation as indicated by the elevated plasma levels of elastase-α 1-proteinase inhibitor complex in some patients. This release might be in part due to the effect of “uremic toxins”. In the patients on hemodialysis treatment the contact of the blood with the dialyzer (cuprophane) membrane might be an additional factor. Moreover, in the patients with acute renal failure the underlying disease (infection, shock, trauma) contributes to the release of proteinases. These disturbances may be harmful to the patient if the blood concentration or function of the most important proteinase inhibitors (α 1-proteinase inhibitor,α 2-macroglobulin) is reduced.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 63 (1985), S. 948-958 
    ISSN: 1432-1440
    Keywords: Alcoholism ; Fetal alcohol syndrome ; Genitourinary tract malformations ; Phosphate and magnesium depletion ; Rhabdomyolysis ; Acute renal failure ; Hypertension ; Alkohol ; Alkoholische Embryopathie ; Urogenitaltraktschädigung ; Phosphatund Magnesiumdepletion ; Rhabdomyolyse ; Akutes Nierenversagen ; Hypertonie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nephrologisch wichtige Störungen des schwereren Alkoholismus manifestieren sich auf verschiedenen Ebenen. Eine direkte Schädigung der Nieren und abführenden Harnwege ist bislang ausschließlich bei alkoholischer Embryopathie nachgewiesen. Beim Erwachsenen dominieren unspezifische und komplexe Elektrolytstörungen mit Akzentuierung im Alkohol-Entzugssyndrom. Die Niere ist nicht selten primäre Ursache verschiedener Störungen, sie trägt ferner zur — oft inadäquaten — Kompensation extrarenal entstandener Stoffwechselstörungen (z.B. Phosphatmangel, Hypoglykämie) bei. Der alkoholassoziierten Uratretention, hervorgerufen durch Hyperlaktatämie oder Erhöhung derβ-Hydroxybuttersäure, kommt — wegen meist mäßiger Ausprägung — für die Entwicklung einer hyperurikämischen Nephropathie nur geringe Bedeutung zu. Alkoholexzeß (akut oder chronisch) prädisponiert zur Rhabdomyolyse mit konsekutivem Nierenversagen. Möglicherweise ist bei schwerem Alkoholismus und Myopathie die Vulnerabilität der Nieren für andere Noxen gesteigert. Bei der Ratte wird das Glyzerin-induzierte akute Nierenversagen durch Alkoholvorbehandlung verstärkt. Alkohol begünstigt ferner bei Normotonikern und Hypertonikern einen Blutdruckanstieg, der seinerseits das Risiko einer Nierenschädigung erhöht.
    Notes: Summary Different nephrological derangements are observed in severe alcoholics. Until now the direct toxicity of ethanol is only shown in the fetal alcohol syndrome with various malformations of the genitourinary tract. In the adult the kidney is often involved in the development, maintenance and counterregulation of complex electrolyte disturbances like phosphate and potassium hypoglycemia etc. The alcohol associated retention of urate, induced by hyperlactatemia and/or increasedβ-hydroxybutyrate concentration is only rarely complicated by urate nephropathy. Alcohol intoxication (acute and chronic) predisposes to rhabdomyolysis with the risk of acute renal failure. There are some hints that chronic alcoholism with myopathy increases the vulnerability of the kidney for further toxic agents. In rats glycerol induced renal failure is enhanced by alcohol pretreatment. Finally, regular alcohol consumption raises the blood pressure, which per se is a risk factor for renal damage.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 64 (1986), S. 579-586 
    ISSN: 1432-1440
    Keywords: Carnitine ; Carnitine esters ; Carnitine palmityl transferase ; Hemodialysis ; Peritoneal dialysis ; End-stage renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Carnitine metabolism is altered in renal insufficiency and influenced by the treatment modalities. Chronically uremic patients with end-stage renal disease under conservative therapy, hemodialysis, or peritoneal dialysis show low, normal, or elevated serum levels of TC and a distorted pattern of FC, SCAC, and LCAC. HD induces a marked depletion of FC, while predialytic elevated SCAC and LCAC are in the normal range at the end of dialysis treatment. All carnitine fractions rapidly return to predialysis levels 6 h after HD due to a transport of carnitine from muscle stores to plasma pool. Muscle carnitine content is elevated in chronic uremic patients under conservative therapy. Normal or decreased levels are observed in patients on long-term HD treatment. In addition, weekly losses of carnitine in patients undergoing HD or peritoneal dialysis do not exceed urinary carnitine excretion of CO. Supplementation with currently recommended doses (1–2 gl-carnitine i.v. at the end of each HD) is followed by a marked rise in plasma carnitine levels, suggesting limited carnitine utilization in uremia. Therefore, lower carnitine doses and modified application regimens should be considered to avoid exaggerated plasma levels of carnitine and carnitine esters. Furthermore, carnitine application has been reported to show beneficial, worsening, or no effect on the deranged lipid metabolism of the uremic patients. In patients undergoing CAPD or IPD predominantly normal serum carnitine levels have been reported. On the other hand, SCAC and LCAC esters are markedly elevated in these patients. After kidney transplantation the pattern of carnitine fractions is fully normalized in patients with plasma creatinine ≤120 µmol/l. Increased levels for TC and its ester fractions are observed in case of an impaired kidney function. Acute renal failure due to massive rhabdomyolysis may occur in rare cases of CPT deficiency.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 59 (1981), S. 761-763 
    ISSN: 1432-1440
    Keywords: Kallikrein excretion ; Alpha1-antitrypsin ; Hypertension ; Renal insufficiency ; Kallikreinexkretion ; Alpha1-Antitrypsin ; Hypertonie ; Niereninsuffizienz
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 100 Patienten, die sich in unserer nephrologischen Ambulanz zur Abklärung einer Hypertonie, Proteinurie oder Erythrozyturie vorstellten, wurde im 24-h-Urin die proteolytische Aktivität vor und nach Zugabe von 0,4 IE Kallikrein (Padutin) ermittelt. Parallel wurden Protein- und alpha1-Antitrypsin-Konzentration im Urin gemessen. Dabei ließ sich eine inverse Beziehung zwischen Kallikrein-Aktivität und alpha1-Antitrypsin-Konzentration in den untersuchten Urinproben aufzeigen (r=0,84;y=39,2e −0,009x). Es bestand ferner eine inverse Korrelation zwischen Kallikrein-Aktivität und 24-h-Ausscheidung von alpha1-Antitrypsin (r=0,81;y=886,4e −0,011x). Unsere Daten sprechen für eine Inaktivierung von renalem Kallikrein durch alpha1-Antitrypsin im Urin.
    Notes: Summary Proteolytic activity, with azocasein as substrate in the presence and absence of 0.4 IU kallikrein (Padutin) was measured in the 24 h urine fractions of 100 ambulatory patients with hypertension, proteinuria or haematuria. Urinary protein and alpha1-antitrypsin concentration have also been assayed. There was an inverse relationship between kallikrein activity and urinary alpha1-antitrypsin concentration (r=0.84;y=39.2e −0.009x). Furthermore, kallikrein activity and 24 h urinary alpha1-antitrypsin excretion were also inversely correlated (r=0.81;y=886.4e −0.011x). Our data suggest an inactivation of renal kallikrein by urinary alpha1-antitrypsin.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 61 (1983), S. 633-640 
    ISSN: 1432-1440
    Keywords: Calcium antagonists ; Nifedipine ; Verapamil ; Diltiazem ; Effects in experimental and essential hypertension ; Side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Calcium antagonists (nifedipine, verapamil, diltiazem) are potent vascular smooth muscle relaxants. Experimental and clinical investigations provide growing evidence that they are effective in acute and (sub)chronic therapy of arterial hypertension by lowering peripheral vascular resistance and improvement of altered hemodynamics — independent from pathogenesis of hypertension. Due to its prompt and profound hypotensive action, sublingual or oral nifedipine has been used successfully in hypertensive crises. The hypotensive effect usually correlates closely with the severity of hypertension and is nearly absent in normotensive controls. Since the blood pressure drop may occasionally result in absolute or relative hypotension, the initial dose should be as low as possible. The activation of the adrenergic and renin angiotensin systems seen after nifedipine administration is less pronounced after chronic administration of the drug and is nearly absent after verapamil and diltiazem. Plasma aldosterone concentrations remain constant or are slightly decreased. In contrast to classic vasodilators, the long-term administration of calcium antagonists usually does not result in tachycardia (nifedipine), but slight sinus bradycardia (verapamil, diltiazem). Peripheral edema may occasionally occur after nifedipine. A tolerance has been observed during long-term treatment of hypertension. Combining these drugs (verapamil, diltiazem) with betablockers is not recommended due to the negative inotropic and bathmotropic effects. Simultaneous administration of nifedipine and beta-blockers enhances the hypotensive action, but favours the development of peripheral edema and in rare cases (especially in severe coronary heart disease) results in a dramatic drop in blood pressure and/or congestive heart failure. Further clinical evaluation and long-term trials of calcium antagonists as antihypertensive agents will be needed before definite conclusions can be drawn.
    Type of Medium: Electronic Resource
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