Hans Köhler

Monocyte heterogeneity in obesity and subclinical atherosclerosis.

AIMSnMonocytes and monocyte-derived macrophages have been recognised as the cellular hallmark of atherosclerosis decades ago. Recently, they have also been shown to play a pivotal role in obesity. Monocytes display immunophenotypic heterogeneity with functionally distinct subpopulations. We initiated the I LIKE HOMe study to examine monocyte heterogeneity in obesity and subclinical atherosclerosis.nnnMETHODS AND RESULTSnWe assessed carotid intima media thickness (IMT), body mass index (BMI), and other cardiovascular risk factors in 622 healthy volunteers. Using flow-cytometry, we differentiated monocytes into CD14(++)CD16(-) and CD16(+) cells, which we further subdivided into CD14(++)CD16(+) and CD14((+))CD16(+) cells. Body mass index was significantly correlated with carotid IMT. High CD16(+) monocyte counts were significantly associated with both higher BMI and increased carotid IMT. Adjustment for CD16(+) monocyte counts weakened the correlation between BMI and carotid IMT, suggesting that the increase in CD16(+) monocyte numbers in obesity may partly explain the association between obesity and IMT.nnnCONCLUSIONnOur results reveal a significant univariate association between CD16(+) monocytes and both obesity and subclinical atherosclerosis in low-risk individuals. They are in line with recent observations that CD16(+) monocytes show high endothelial affinity and a potent capacity to invade vascular lesions and to transform into pro-inflammatory cytokine producing macrophages.

Reduction of cisplatin toxicity in cultured renal tubular cells by the bioflavonoid quercetin.

Abstract Quercetin (QC), a polyphenolic compound widely distributed in fruits and vegetables has recently gained interest due to its cisplatin (CP) sensitizing properties in cancer cells. It is currently unknown, whether quercetin also increases the susceptibility of the kidneys to cisplatin toxicity. We studied the effects of various bioflavonoids on CP toxicity in an in vitro model of cultured tubular epithelial cells (LLC-PK1). Viability of LLC-PK1 cells, as assessed by lactate dehydrogenase (LDH) release and MTT-test, was affected by CP (100–400u2009μM) in a time and dose dependent fashion. Pretreatment of cells with QC for 3 h significantly reduced the extent of cell damage. The protective activity of QC was concentration dependent, starting at 10–25 μM and reaching a plateau between 50 and 100u2009μM. Other bioflavonoids (catechin, silibinin, rutin) did not diminish cellular injury, even at higher concentrations (100–500u2009μM). Quercetin itself showed some intrinsic cytotoxicity at concentrations exceeding 75u2009μM. Our data indicate that quercetin reduces cisplatin toxicity in cultured tubular epithelial cells. The exact mechanism of protection is unclear, though scavenging of free oxygen radicals may play an important role.

Effect of quercetin on hypoxic injury in freshly isolated rat proximal tubules

The bioflavonoid quercetin, which has antioxidant properties, protects renal tubular epithelial cells from oxidant-induced injury by inhibiting lipid peroxidation. We examined the effect of quercetin on hypoxia-induced injury in freshly isolated rat renal proximal tubules. Hypoxia induced rapid loss of cellular ATP, followed by functional and structural alterations measured as a decrease in tubular potassium content and sequentially by an increase in lactate dehydrogenase release. Furthermore, hypoxia increased lipid peroxidation, measured as thiobarbituric acid-reactive substances. Quercetin significantly inhibited hypoxia-induced functional and structural tubular injury in addition to lipid peroxidation but did not alter hypoxia-induced ATP depletion. These results demonstrate the potency of the bioflavonoid quercetin in protecting proximal tubules from hypoxic injury, which is independent of tubular energy metabolism and may be related to the inhibition of lipid peroxidation.

Heat-preconditioning confers protection from Ca2+-mediated cell toxicity in renal tubular epithelial cells (BSC-1)

A rise in intracellular calcium may mediate ischemic damage by phospholipid hydrolysis and proteolysis. Heat shock proteins have been shown to provide protection from various forms of cell stress, but not from models of Ca(2+)-mediated injury. The effect of heat preconditioning in a model of ionomycin-induced injury in cultured renal tubular epithelial cells (BSC-1) was examined. Hsp70-mRNA expression was induced by hyperthermia (HT) (42 degrees C, 60 min). Hsp70 protein accumulation was maximal after 12-18 h and returned to baseline levels by 96 h. Treatment of BSC-1 cells with ionomycin (7.0 microM) produced lethal cell injury characterized by LDH release. Cells examined at 18 h after HT were significantly less damaged than cells studied at 96 h after HT. Our data are the first to demonstrate that heat preconditioning confers protection from Ca(2+)-mediated cell injury. The state of increased tolerance is transient and closely parallels kinetics of Hsp70 expression.

Malnutrition bei Hämodialysepatienten

BACKGROUNDnMalnutrition in hemodialysis patient is associated with increased mortality and morbidity. Inventions to treat malnutrition are often ineffective. Underestimation by the patients of the importance of dietary interventions might negatively influence any therapeutic outcome. We examined the correlation between nutritional assessment by the patient himself and clinical assessment by the physician.nnnPATIENTS AND METHODSnSubjective global assessment (SGA) was performed in 68 chronic hemodialysis patients Serum concentrations of albumin, prealbumin, transferrin and cholesterin were measured Protein intake was estimated by protein catabolic rate (nPCR). In form of a questionnaire patients were asked to assess then own nutrition.nnnRESULTSnAccording to SGA-criteria, moderate to severe malnutrition was found in 34% of our patients. In this unauthorized group serum albumin was < 4.0 g/dl in 45% of patients and correlated best with clinical nutritional assessment. Specificity was lower for prealbumin, transferrin, cholesterin, and nPCR. The questionnaire was completed by 85% of patients. Self-assessment of their own nutrition was discrepant to clinical assessment in 84% of malnourished patients. A similar percentage (79%) of malnourished patients considered their own body weight to be adequate, while only 21% indicated desire to gain weight.nnnCONCLUSIONSnOur data indicate that a significant percentage of malnourished hemodialysis patients shows a tendency to overestimate their own nutrition. This may negatively influence patient compliance and should be considered in dietary counseling of malnourished chronic hemodialysis patients.ZusammenfassungHintergrundDas Auftreten einer Malnutrition bei Dialysepatienten geht mit erhöhter Morbidität und Mortalität einher. Die Therapie einer Mangelernährung bleibt jedoch häufig erfolglos, was durch mangelndes Verständnis des Patienten für die Notwendigkeit einer diätetischen Intervention bedingt sein könnte. Wir untersuchten in dieser Studie, inwieweit die Beurteilung der Ernährung durch Patienten und Arzt übereinstimmt.Patienten und MethodeBei 68 chronischen Dialysepatienten wurde der Ernährungsstatus mittels „Subjective Global Assessment” (SGA) erhoben. Im Serum wurden Albumin, Präalbumin, Transferrin und Cholesterin bestimmt, zusätzlich wurde die „Protein-Catabolic-Rate” (nPCR) ermittelt. Mittels Fragebogen wurden die Patienten um eine Beurteilung ihrer Ernährung und ihres Gewichtes gebeten.ErgebnisNach SGA-Kriterien zeigten 34% der Patienten Zeichen der mäßigen bis schweren Malnutrition, bei 45% lag das Serumalbumin < 4,0 g/dl. Albumin korrelierte am besten mit der klinischen Beurteilung, wohingegen Transferrin, Präalbumin, Cholesterin und Protein-Catabolic-Rate schlechtere Korrelationen zeigten. Der Fragebogen wurde von 85% der Patienten beantwortet. In der nach SGA-Kriterien mangelernährten Gruppe beurteilten 84% die eigene Ernährung als „ausreichend”, 79% waren mit dem eigenen Gewicht zufrieden, lediglich 21% beklagten Untergewicht.SchlußfolgerungUnsere Untersuchung zeigt, daß bei Hämodialysepatienten häufig eine Fehlbeurteilung der eigenen Ernährungssituation vorliegt. Dies sollte bei der Beratung und Führung mangelernährter Patienten berücksichtigt werden.SummaryBackgroundMalnutrition in hemodialysis patients is associated with increased mortality and morbidity. Interventions to treat malnutrition are often ineffective. Underestimation by the patients of the importance of dietary interventions might negatively influence any therapeutic outcome. We examined the correlation between nutritional assessment by the patient himself and clinical assessment by the physician.Patients and MethodsSubjective global assessment (SGA) was performed in 68 chronic hemodialysis patients. Serum concentrations of albumin, prealbumin, transferrin and cholesterin were measured. Protein intake was estimated by protein catabolic rate (nPCR). In form of a questionaire patients were asked to assess their own nutrition.ResultsAccording to SGA-criteria, moderate to severe malnutrition was found in 34% of our patients. In this malnourished group serum albumin was <4.0 g/dl in 45% of patients and correlated best with clinical nutritional assessment. Specificity was lower for prealbumin, transferrin, cholesterin, and nPCR. The questionaire was completed by 85% of patients. Self-assessment of their own nutrition was discrepant to clinicla assessment in 84% of malnourished patients. A similar percentage (79%) of malnourished patients considered their own body weight to be adequate, while only 21% indicated desire to gain weight.ConclusionsOur data indicate that a significant percentage of malnourished hemodialysis patients shows a tendency to overestimate their own nutrition. This may negatively influence patient compliance and should be considered in dietary counseling of malnourished chronic hemodialysis patients.

Therapeutischer Plasmaaustausch 1996

Zusammenfassung□ Der therapeutische Plasmaaustausch (TPA) ist ein extrakorporales Blutreinigungsverfahren zur Entfernung großmolekularer Plasmabestandteile. Seit Ende der siebziger Jahre wurde die Plasmapherese bei einer Vielzahl von Erkrankungen eingesetzt, in deren pathophysiologischem Verständnis humoralen Faktoren eine wesentliche Bedeutung zugeschrieben wird.□ Aus heutiger Sicht ist der Plasmaaustausch als adjuvante Therapie nur bei wenigen Entitäten in bestimmten Krankheitssituationen anerkannt: Antibasalmembranerkrankung, TTP/HUS, Guillain-Barré-Syndrom, Hyperviskositätssyndrom, chronische Polyneuropathie bei IgG- und IgA-Gammopathie, chronisch inflammatorische demyelinisierende Polyneuropathie und Myasthenia gravis.Summary□ Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique to remove large molecular weight substances. Since the late seventies TPE was used in a variety of diseases in which humoral factors may play a part in the pathogenesis.□ Today, accepted indications only exist for a few entities in defined situations: Anti-glomerular basement membrane antibody mediated disease, TTP/HUS, Guillain-Barré-syndrome, hyperviscosity syndrome, chronic polyneuropathy associated with IgG and IgA gammopathy, chronic inflammatory demyelinating polyneuropathy and myasthenia gravis.Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique to remove large molecular weight substances. Since the late seventies TPE was used in a variety of diseases in which humoral factors may play a part in the pathogenesis. Today, accepted indications only exist for a few entities in defined situations: Anti-glomerular basement membrane antibody mediated disease, TTP/HUS, Guillain-Barré-syndrome, hyperviscosity syndrome, chronic polyneuropathy associated with IgG and IgA gammopathy, chronic inflammatory demyelinating polyneuropathy and myasthenia gravis.

Was ist geischert in der Prävention der Kontrastmittelnephropathie

Nephropathy is one of the most important side effects of radiocontrast in patients with impaired renal function. Incidence is reported from 20% to 100% depending on underlying disease. For prevention of radiocontrast nephropathy a large number of substances were investigated in experimental and clinical studies. Clinical relevance of this findings will be assessed by this article. In summary of these studies hydration is the most relevant and significant measure for prevention of radiocontrast nephropathy in patients at risk (i.e. serum creatinine > 1.5 mg/dl). 1 ml/kg body weight/h with 0.45% NaCl 12 h before and after administration of radiocontrast should be supplied. Hemodialysis is recommended if impaired renal function (serum creatinine > 3.5 mg/dl) is accompanied by additional risk factors, e.g. diabetes mellitus. The impact of dialysis therapy is not clarified by clinical studies.ZusammenfassungEine der wichtigsten Kontrastmittelnebenwirkungen ist die akute Verschlechterung einer bereits bestehenden Nierenfunktionseinschränkung. Die Inzidenz liegt in Abhängigkeit der Grunderkrankung zwischen 20% und 100%. In experimentellen und klinischen Studien wurden zahlreiche medikamentöse Therapieansätze zur Prävention der Kontrastmittelnephropathie untersucht. In der vorliegenden übersicht werden diese Maßnahmen hinsichtlich ihrer klinischen Relevanz bewertet. Als Schlußfolgerung dieser Studien kann als einzig gesicherte Maßnahme zur Protektion der Kontrastmittelnephropathie bei Risikopatienten (Ausgangskreatinin > 1,5 mg/dl) eine ausreichende Hydratation empfohlen werden. Sie wird mit 1 ml/kg KG/h mittels 0,45% NaCl zwölf Stunden vor und nach Kontrastmittelapplikation durchgeführt. Bei Patienten mit höhergradiger Nierenfunktionseinschränkung (Serumkreatinin > 3,5 mg/dl) und gleichzeitigem Vorliegen einer zusätzlichen Risikokonstellation (zum Beispiel Diabetes mellitus) wird eine Hämodialysebehandlung nach Kontrastmittelgabe empfohlen. Der Wertr der Dialysebehandlung ist allerdings nicht durch kontrollierte Studien gesichert.SummaryNephropathy is one of the most important side effects of radiocontrast in patients with impaired renal function. Incidence is reported from 20% to 100%, depending on underlying disease. For prevention of radiocontrast nephropathy a large number of substances were investigated in experimental and clinical studies. Clinical relevance of this findings will be assessed by this article. In summary of these studies hydration is the most relevant and significant measure for prevention of radiocontrast nephropathy in patients at risk (i. e. serum creatinine > 1,5 mg/dl). 1 ml/kg body weight/h with 0,45% NaCl 12 h before and after administration of radiocontrast should be supplied. Hemodialysis is recommended if impaired renal function (serum creatinine > 3,5 mg/dl) is accompanied by additional risk factors, e. g. diabetes mellitus. The impact of dialysis therapy is not clarified by clinical studies.