Untargeted Lipidomics Highlight the Depletion of Deoxyceramides during Therapy‐Induced Senescence

Therapy‐induced senescence is a state of cell cycle arrest that occurs as a response to various chemotherapeutic reagents, especially ones that cause DNA damage. Senescent cells display resistance to cell death and can impair the efficacy of chemotherapeutic strategies. Since lipids can exhibit pro‐survival activity, it is envisioned in this article that probing the lipidome could provide insights into novel lipids that are involved in senescence. Therefore, a tissue culture model system is established and the cellular lipidomes of senescent and proliferating cells are comparatively analyzed. Out of thousands of features detected, 17 species are identified that show significant changes in senescent cells. The majority of these species (11 out of 17) are atypical sphingolipids, 1‐deoxyceramides/dihydroceramides, which are produced as a result of the utilization of alanine, instead of serine during sphingolipid biosynthesis. These lipids are depleted in senescent cells. Elevating the levels of deoxyceramides by supplementing the growth medium with metabolic precursors or by directly adding deoxyceramide result in decreased senescence, suggesting that these species might play a key role in this process.     

Yellow nail syndrome: treatment of lymphedema using low pressure compression

The present report describes a case with the triad of yellow nail syndrome (YNS) and the use of low-pressure compression pump as treatment of lymphedema in YNS. A 71-year-old woman presented with bilateral lower extremity lymphedema, yellow nails, and recurrent bilateral pleural effusion. In this case, we specifically focused on lymphedema treatment of the legs besides other recommendations for YNS.     

Detection of coronary microembolization by Doppler ultrasound in patients with stable angina pectoris during percutaneous coronary interventions under an adjunctive antithrombotic therapy with abciximab: design and rationale of the High Intensity Transient Signals ReoPro (HITS-RP) study

Background

Embolization of atherosclerotic debris from the rupture of a vulnerable atherosclerotic plaque occurs iatrogenically during percutaneous coronary interventions (PCI) and can induce myocardial necrosis. These microembolizations are detected as high intensity transient signals (HITS) using intracoronary Doppler technology.

Presentation of the hypothesis

In the presented study we will test if abciximab (ReoPro?) infusion reduces high intensity transient signals in patients with stable angina pectoris undergoing PCI in comparison to standard therapy alone.

Testing the hypothesis

The High Intensity Transient Signals ReoPro? (HITS-RP) study will enroll 60 patients. It is a prospective, single center, randomized, double-blinded, controlled trial. The study is designed to compare the efficacy of intravenous abciximab administration for reduction of microembolization during elective PCI. Patients will be randomized in a 1:1 fashion to abciximab or placebo infusion. The primary end point of the HITS-RP-Study is the number of HITS during PCI measured by intracoronary Doppler wire. Secondary endpoints are bleeding complications, elevation of cardiac biomarkers or ECG changes after percutaneous coronary interventions, changes in coronary flow velocity reserve, hs-CRP elevation, any major adverse cardio-vascular event during one month follow-up.

Implications of the hypothesis

The HITS-RP-Study addresses important questions regarding the efficacy of intravenous abciximab administration in reducing microembolization and periprocedural complications in stable angina pectoris patients undergoing PCI.

Trial registration

The trial is registered under http://www.drks-neu.uniklinik-freiburg.de/drks_web/:DRKS00000603.     

Alterations in promoter methylation status of tumor suppressor HIC1, SFRP2, and DAPK1 genes in prostate carcinomas

Hypermethylated genomic DNA is a common feature in tumoral tissues, although the prevalence of this modification remains poorly understood. We aimed to determine the frequency of five tumor suppressor (TS) genes in prostate cancer and the correlation between promoter hypermethylation of these genes and low and high grade of prostate carcinomas. A total of 30 prostate tumor specimens were investigated for promoter methylation status of TS hypermethylated in cancer 1 (HIC1), death-associated protein kinase 1 (DAPK1), secreted frizzled-related protein 2 (SFRP2), cyclin-dependent kinase inhibitor 2A (p16), and O-6-methylguanine-DNA methyltransferase (MGMT) genes by using bisulfite modifying method. A high frequency of promoter hypermethylation was found in HIC1 (70.9%), SFRP2 (58.3%), and DAPK1 (33.3%) genes in tumor samples that were examined. The current data show high frequency of hypermethylation changes in HIC1, SFRP2, and DAPK1 genes in prostate carcinomas of high Gleason Score (GS).     

The effect of taurine on mesenteric blood flow and organ injury in sepsis

Endotoxin decreases mesenteric blood flow and inflicts organ injury via free radicals. We investigated whether taurine, an endogenous antioxidant and vasodilator, could attenuate the deleterious effects of endotoxin in a mouse model of sepsis. Swiss albino mice were allocated into four groups and treated either with taurine (150 mg/kg, i.p. at 0(th), 8(th), 16(th) h) or its solvent sterile saline (NaCl 0.9%, w/v) while E. coli endotoxin (20 mg/kg, i.p.) or its solvent saline were also given at 8(th) h. At 24(th) h the animals were anaesthetized and the mesenteric blood flow was measured by using perivascular ultrasonic Doppler-flowmeter. The animals were then exsanguinated, the spleen, liver, and kidneys were isolated for histopathological examination. Thiobarbituric acid-reacting substances (TBARS), glutathione, and myeloperoxidase activity were determined in the liver samples. Endotoxin significantly decreased the mesenteric blood flow and glutathione levels in liver while TBARS and myeloperoxidase activity were increased. However, taurine did not block the deleterious effects of endotoxin nor it did attenuate the histopathological injury. Therefore, we concluded that endotoxin-induced organ injury via free radicals is resistant to blockade by taurine.     

Leptin Does Not Play a Major Role in Platelet Aggregation in Obesity and Leptin Deficiency

Objective: A recent study suggested that high concentrations of leptin enhance platelet aggregations. Therefore, the aim of this study was to investigate whether platelet aggregation is altered in patients with leptin gene mutations compared with obese subjects or controls. Research Methods and Procedures: Four men (one homozygous man and his three heterozygous brothers) carrying a leptin gene mutation; 20 age‐matched, healthy, unrelated men; and 18 age‐matched obese men were enrolled in the study. Adenosine diphosphate (ADP)‐, collagen‐, and epinephrine‐induced platelet aggregation were evaluated in all individuals. Results: Our results show that patients with the leptin gene mutation (both the homozygous and heterozygous patients) had significantly higher ADP‐induced (78.3 ± 3.4% vs. 57.9 ± 9.3%, p = 0.001), collagen‐induced (78.1 ± 2.9% vs. 56.7 ± 9.3%, p = 0.007), and epinephrine‐induced (76.5 ± 9.2% vs. 59.5 ± 7.70%, p = 0.003) platelet aggregation compared with controls. However, ADP‐, collagen‐, or epinephrine‐induced platelet aggregations were similar to those in obese patients. Platelet aggregation responses to a combination of pretreatment with leptin at concentrations of 20, 50, 100, or 500 ng/mL for 5 minutes and ADP at concentrations of 2 μmol/liter also were evaluated. However, we did not find significant increases in platelet aggregation even at high concentrations of leptin (100 or 500 ng/mL) in leptin‐deficient patients, obese subjects, or controls. Discussion: Our data show that similar to findings in obese humans, homozygous or heterozygous leptin deficiency is associated with increased platelet aggregation compared with controls, and that higher concentrations of leptin do not increase platelet aggregation.     

Effects of Kaolin (M-99-099) Application on Antioxidant and Phenolic Compounds in Tea Leaves (<Emphasis Type="Italic">Camellia sinensis</Emphasis> L.O. Kuntze)

In this study, the effects of kaolin (M-99-099) applications on the total phenolic and antioxidant contents of tea leaves (Camellia sinensis (L.) O. Kuntze) harvested in three different periods were investigated. For this purpose, four different strategies including standard fertilizer application (T), 3% kaolin+standard fertilizer application (Ka₁), 6% kaolin+standard fertilizer application (Ka₂), and control (C) (nothing applied) were used to compare the effects of these strategies on total phenolic content, FRAP values, and DPPH radical scavenging capacities of tea leaves. It has been proven that the kaolin applications, Ka₁ and Ka₂, increase the phenolic content and antioxidant contents of tea samples. While the kaolin applications have higher values at 1st harvest than those of T and C, they have the lowest values at 3rd harvest.