Zelltherapeutika – eine innovative Therapieoption in der Ophthalmologie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Veränderungen und Erkrankungen der Hornhaut (Cornea) zählen zu den häufigsten Ursachen schwerer Sehbehinderung und...     

The Redox Modulating Sonlicromanol Active Metabolite KH176m and the Antioxidant MPG Protect Against Short-Duration Cardiac Ischemia-Reperfusion Injury

Cardiovascular Drugs and Therapy - Sonlicromanol is a phase IIB clinical stage compound developed for treatment of mitochondrial diseases. Its active component, KH176m, functions as an antioxidant,...     

On the atrial response to focal discharges in man

INTRODUCTION: Triggers and vulnerability are key factors for the occurrence of atrial fibrillation (AF). The aim of this study was to assess spatial dispersion of atrial refractoriness and vulnerability in response to both focal discharges as well as programmed electrical stimulation in patients undergoing ablation of atrial arrhythmogenic foci. METHODS AND RESULTS: Twenty-nine patients were studied, and 12 right atrial unipolar electrograms were recorded. Inducibility of AF was assessed by a pacing protocol that started with one extrastimulus, followed by more aggressive pacing until AF was obtained. Mean fibrillatory intervals were used to assess the local refractoriness of each recording site. Spatial dispersion of refractoriness was calculated as the coefficient of dispersion (CD value: standard deviation of the mean of all local mean fibrillatory intervals as a percentage of the overall mean fibrillatory interval). Based on our previous study, a CD value 3.0 was considered enhanced spatial dispersion of refractoriness. Fifteen of 29 patients had normal dispersion of refractoriness (mean CD value 1.65 +/- 0.43), and AF was inducible with burst pacing only. These patients had focal discharges causing rapid atrial tachycardia with a focal activation pattern. Activation mapping of focal activity was possible in 14 of 15 patients. Focal triggering of AF occurred in only 1 of 15 patients. Fourteen of 29 patients had enhanced dispersion (mean CD value 4.2 +/- 0.72). AF was inducible with a single extrastimulus in 11 of 14 patients (P < 0.001). Focal triggering of AF occurred in all 14 patients. CONCLUSION: Spatial dispersion of atrial refractoriness determines whether focal atrial discharges trigger AF with disorganized activity or, alternatively, only rapid atrial tachycardia.     

The suprachiasmatic nucleus generates the diurnal changes in plasma leptin levels

At present it is not clear which factors are responsible for the diurnal pattern of plasma leptin levels, although the timing of food intake and circulating hormones such as glucocorticoids and insulin have both been proposed as independent determinants. In this study we show that ablation of the biological clock by thermal lesions of the hypothalamic suprachiasmatic nucleus (SCN) completely eliminates the diurnal pattern of plasma leptin levels. By contrast, removal of the diurnal corticosterone signal by adrenalectomy and corticosterone replacement did not affect diurnal plasma leptin levels. More importantly, removal of the nocturnal feeding signal by submitting the animals to a regular feeding schedule of six meals per day did not abolish the diurnal plasma leptin levels. However, both SCN lesions and the regular feeding schedule did cause an increase in the 24-h mean plasma leptin levels. As neither rhythmic feeding, insulin, or corticosterone signals can completely explain the diurnal plasma leptin rhythm, we conclude that biological clock control of the sympathetic input to the adipocyte is essential for regulation of the daily rhythm in leptin release.     

Clinical features of galactokinase deficiency:A review of the literature

Summary: Galactokinase deficiency (McKusick 230200) is a rare autosomal recessive inborn error of galactose metabolism. Cataract and, rarely, pseudotumor cerebri caused by galactitol accumulation seem to be the only consistently reported abnormalities in this disorder. We performed a literature search to obtain information on the clinical spectrum of galactokinase deficiency. A total of 25 publications were traced describing 55 galactokinase-deficient patients. Cataract was reported in most patients. Clinical abnormalities other than cataract were reported in 15 (35%) out of 43 cases on which information was available. However, all symptoms were reported infrequently and a causal relationship with the galactokinase deficiency is unlikely. As cataract and pseudotumor cerebri appear to be the sole complications of galactokinase deficiency, the outcome for patients with galactokinase deficiency is much better than for patients with classical galactosaemia (McKusick 230400), a more common autosomal recessive disorder of galactose metabolism caused by galactose-1-phosphate uridyltransferase (GALT; EC 2.7.7.12) deficiency. Long-term follow-up of patients with this disorder has shown that, in spite of a severely galactose-restricted diet, most patients develop abnormalities such as a disturbed mental and/or motor development, dyspraxia and hypergonadotropic hypogonadism. Endogenous production of galactose has been considered an important aetiological factor. Although damage may well occur inutero, available evidence suggests that damage will continue after birth. Inhibition of galactokinase may then be a promising approach for controlling damage in GALT-deficient patients.     

Biochemical Urine Testing of Medication Adherence and Its Association With Clinical Markers in an Outpatient Population of Type 2 Diabetes Patients: Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT)

OBJECTIVETo assess adherence to the three main drug classes in real-world patients with type 2 diabetes using biochemical urine testing, and to determine the association of nonadherence with baseline demographics, treatment targets, and complications.RESEARCH DESIGN AND METHODSAnalyses were performed of baseline data on 457 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT) study. Adherence to oral antidiabetics (OADs), antihypertensives, and statins was determined by analyzing baseline urine samples using liquid chromatography–tandem mass spectrometry. Primary outcomes were microvascular and macrovascular complications and treatment targets of LDL cholesterol, HbA_1c, and blood pressure. These were assessed cross-sectionally at baseline.RESULTSOverall, 89.3% of patients were identified as adherent. Adherence rates to OADs, antihypertensives, and statins were 95.7%, 92.0%, and 95.5%, respectively. The prevalence of microvascular (81.6% vs. 66.2%; P = 0.029) and macrovascular complications (55.1% vs. 37.0%; P = 0.014) was significantly higher in nonadherent patients. The percentage of patients who reached an LDL cholesterol target of ≤2.5 mmol/L was lower (67.4% vs. 81.1%; P = 0.029) in nonadherent patients. Binary logistic regression indicated that higher BMI, current smoking, elevated serum LDL cholesterol, high HbA_1c, presence of diabetic kidney disease, and presence of macrovascular disease were associated with nonadherence.CONCLUSIONSAlthough medication adherence of real-world type 2 diabetes patients managed in specialist care was relatively high, the prevalence of microvascular and macrovascular complications was significantly higher in nonadherent patients, and treatment targets were reached less frequently. This emphasizes the importance of objective detection and tailored interventions to improve adherence.     

Neurological disease caused by Oropouche virus in northern Brazil: should it be included in the scope of clinical neurological diseases?

Journal of NeuroVirology - We describe two neurological cases of Oropouche virus infection in northern Brazil, where the virus is endemic but neglected as a pathogen. This study reiterates the...