Cornelius Bollheimer

Lipid accumulation in hepatocytes induces fibrogenic activation of hepatic stellate cells

Despite the initial belief that non-alcoholic fatty liver disease is a benign disorder, it is now recognized that fibrosis progression occurs in a significant number of patients. Furthermore, hepatic steatosis has been identified as a risk factor for the progression of hepatic fibrosis in a wide range of other liver diseases. Here, we established an in vitro model to study the effect of hepatic lipid accumulation on hepatic stellate cells (HSCs), the central mediators of liver fibrogenesis. Primary human hepatocytes were incubated with the saturated fatty acid palmitate to induce intracellular lipid accumulation. Subsequently, human HSCs were incubated with conditioned media (CM) from steatotic or control hepatocytes. Lipid accumulation in hepatocytes induced the release of factors that accelerated the activation and proliferation of HSC, and enhanced their resistance to apoptosis, largely mediated via activation of the PI-3-kinase pathway. Furthermore, CM from steatotic hepatocytes induced the expression of the profibrogenic genes TGF-β, tissue inhibitor of metallo-proteinase-1 (TIMP-1), TIMP-2 and matrix-metallo-proteinase-2, as well as nuclear-factor κB-dependent MCP-1 expression in HSC. In summary, our in vitro data indicate a potential mechanism for the pathophysiological link between hepatic steatosis and fibrogenesis in vivo. Herewith, this study provides an attractive in vitro model to study the molecular mechanisms of steatosis-induced fibrogenesis, and to identify and test novel targets for antifibrotic therapies in fatty liver disease.

Vitamin D Deficiency Reduces the Immune Response, Phagocytosis Rate, and Intracellular Killing Rate of Microglial Cells

ABSTRACT Meningitis and meningoencephalitis caused by Escherichia coli are associated with high rates of mortality and neurological sequelae. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. Vitamin D has potent effects on human immunity, including induction of antimicrobial peptides (AMPs) and suppression of T-cell proliferation, but its influence on microglial cells is unknown. The purpose of the present study was to determine the effects of vitamin D deficiency on the phagocytosis rate, intracellular killing, and immune response of murine microglial cultures after stimulation with the Toll-like receptor (TLR) agonists tripalmitoyl-S-glyceryl-cysteine (TLR1/2), poly(I·C) (TLR3), lipopolysaccharide (TLR4), and CpG oligodeoxynucleotide (TLR9). Upon stimulation with high concentrations of TLR agonists, the release of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was decreased in vitamin D-deficient compared to that in vitamin D-sufficient microglial cultures. Phagocytosis of E. coli K1 after stimulation of microglial cells with high concentrations of TLR3, -4, and -9 agonists and intracellular killing of E. coli K1 after stimulation with high concentrations of all TLR agonists were lower in vitamin D-deficient microglial cells than in the respective control cells. Our observations suggest that vitamin D deficiency may impair the resistance of the brain against bacterial infections.

Gender-specific differences in the development of sarcopenia in the rodent model of the ageing high-fat rat

Sarcopenia is linked to functional impairments, loss of independence, and mortality. In the past few years, obesity has been established as being a risk factor for a decline in muscle mass and function. There are several molecular pathological mechanisms, which have been under discussion that might explain this relationship. However, most studies were conducted using male animals and for a short period of time.

Principles of the prolactin/vasoinhibin axis

The hormonal family of vasoinhibins, which derive from the anterior pituitary hormone prolactin, are known for their inhibiting effects on blood vessel growth, vasopermeability, and vasodilation. As pleiotropic hormones, vasoinhibins act in multiple target organs and tissues. The generation, secretion, and regulation of vasoinhibins are embedded into the organizational principle of an axis, which integrates the hypothalamus, the pituitary, and the target tissue microenvironment. This axis is designated as the prolactin/vasoinhibin axis. Disturbances of the prolactin/vasoinhibin axis are associated with the pathogenesis of retinal and cardiac diseases and with diseases occurring during pregnancy. New phylogenetical, physiological, and clinical implications are discussed.

[Hormone-induced spontaneous femoral neck fracture in a 28-year-old female patient].

ZusammenfassungFallbeschreibung:Eine 28-jährige Patientin wurde bei lateraler Schenkelhalsspontanfraktur ohne adäquates Trauma ins Krankenhaus eingewiesen. Die durchgeführte Knochendichtemessung zeigte eine Osteoporose ohne erkennbare Ursache oder eindeutige Risikofaktoren. Die endokrinologische Abklärung erbrachte die Diagnose eines Hyperkortisolismus. Schließlich konnte ein Morbus Cushing diagnostiziert werden, und es erfolgte eine transsphenoidale Hypophysenresektion. Die Patientin erhielt eine Osteoporosetherapie mit Vitamin-D- und Calciumsubstitution sowie Bisphosphonaten.Schlussfolgerung:Die glukokortikoidinduzierte Osteoporose ist eine der häufigsten sekundären Osteoporoseformen. Fälle mit okkultem endogenen Cushing-Syndrom und manifester Osteoporose als einzige Manifestation der Erkrankung sind beschrieben, wenn auch sehr selten. Daher sollte bei Osteoporose unklarer Ursache ein Hyperkortisolismus ausgeschlossen werden.AbstractCase Report:A 28-year-old woman was referred to hospital with a spontaneous femoral neck fracture. Dual energy X-ray absorptiometry showed severe osteoporosis without apparent cause or risk factors. The basic endocrinologic evaluation revealed hypercortisolism, and the diagnosis of Cushing’s disease could be made following biochemical test and magnetic resonance imaging. A transsphenoidal resection of the pituitary gland tumor was performed and led to a cure of the disease. The patient received calcium and vitamin D substitution as well as biphosphonates.Conclusion:Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Only few cases with occult endogenous Cushing’s syndrome and osteoporosis as the main manifestation of the disease have been reported. Nevertheless, hypercortisolism should be excluded whenever osteoporosis without apparent cause is diagnosed.

Testosteron im Alter – ein Update

Contrasting the relatively abrupt hormonal changes during female menopause, male reproductive function gradually declines during aging. This leads to the formal diagnosis of androgen deficiency in many apparently healthy 80-year-old men, when conventional thresholds are applied, and consequently to the question of androgen substitution in geriatric medicine. Although many clinical studies have documented a correlation between low plasma testosterone levels and mortality a clear causal relationship - which would imply immanent substitution therapy - has not been demonstrated. With this in mind, the diagnosis of late-onset hypogonadism (LOH) should only be made when testosterone-deficiency related symptoms concur with low testosterone levels. Which exact symptoms justify the diagnosis of LOH, however, is not sharply defined. Using criteria defined in the recent EMAS study, LOH might even be an over-diagnosed entity without huge relevance in geriatrics. Low testosterone levels are associated with frailty, but testosterone supplementation has only shown limited effects on age-related sarcopenia. Moreover: the increased incidence of cardiovascular events in the TOM study should be a caveat and lead to a moratorium for uncritical testosterone supplementation in aging men with cardiovascular diseases.

Behandlung des Typ-2-Diabetes beim alten Patienten

ZusammenfassungHintergrundDer Typ-2-Diabetes ist eine mit zunehmendem Alter häufiger auftetende Erkrankung, die zwar auch durch genetische Disposition und altersassoziierte Veränderungen, besonders aber durch die Lebensumstände des Betroffenen beeinflusst wird.Ziel der ArbeitEs wird der Frage nachgegangen, welche Evidenz für Besonderheiten der Therapie des Typ-2-Diabetes im höheren Patientenalter besteht.Material und MethodenGrundlagen der Arbeit bilden die Literaturbasis und die Leitlinien der Deutschen Diabetes-Gesellschaft (DDG).ErgebnisseNicht zuletzt aufgrund der erwarteten demografischen Veränderungen rückt die Diabeteserkrankung im fortgeschrittenen Lebensalter zunehmend ins Bewusstsein. Die therapeutischen Optionen bei älteren Patienten mit Diabetes müssen in Abhängigkeit von erreichbaren Therapiezielen und Komorbiditäten, insbesondere einer eingeschränkten Nierenfunktion, beurteilt werden.AbstractBackgroundType 2 diabetes is a disease which occurs more frequently with increasing age and is particularly influenced by the lifestyle of those affected in addition to a genetic disposition and age-related alterations.AimThe purpose of this article is to discuss the evidence for special characteristics of the therapy of type 2 diabetes in elderly patients.Material and methodsThe study is based on a literature survey and the guidelines of the“Deutsche Diabetes-Gesellschaft” (DDG, German Diabetes Society).ResultsThere is increasingly more awareness of diabetes in advanced age not least due to the expected demographic changes. The therapeutic options in older patients with diabetes must be assessed depending on the achievable targets of therapy and comorbidities, in particular limited renal function.

Messung des Knöchel-Arm-Index (ankle brachial index; ABI)

Unter praxisrelevanten Gesichtspunkten fur den Diabetes mellitus mit zusatzlich bestehender peripherer arterieller Verschlusskrankheit wird die Messung des Knochel-Arm-Index, auch genannt ABI (ankle brachial index), dargestellt unter ubersichtlicher Zusammenstellung der exakten Vorgehensweise und der Grenzwerte.

Klassifikation des GdB (Grad der Behinderung) bei Endokrinopathien

Unter Fokussierung auf den Diabetes mellitus werden knapp und ubersichtlich die Kriterien zur Klassifikation des GdB (Grad der Behinderung) zusammengefasst.

Perzentilendokumentation bei Kindern und Jugendlichen

Praxisnah wird die bei Kindern und Jugendlichen erforderliche geschlechter-getrennte Dokumentation von Grose, Gewicht und Wachstumsgeschwindigkeit in Perzentilen darstellt und in Bezug gesetzt zu Erkrankungen wie Wachstumshormonmangel, konstitutionelle Entwicklungsverzogerung (KEV) aber auch zum Knochenalter.