L-Propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage protector

L-Propionylcarnitine, a propionyl ester of L-carnitine, increases the intracellular pool of L-carnitine. It exhibits a high affinity for the enzyme carnitine acetyltransferase (CAT) and, thus, is readily converted into propionyl-coenzyme A and free carnitine. It has been reported that L-propionylcarnitine possesses a protective action against heart ischemia–reperfusion injury; however, the antioxidant mechanism is not yet clear. L-Propionylcarnitine might reduce the hydroxyl radical production in the Fenton system, by chelating the iron required for the generation of hydroxyl radicals. To obtain a better insight into the antiradical mechanism of L-propionylcarnitine, the present research analyzed the superoxide scavenging capacity of L-propionylcarnitine and its effect on linoleic acid peroxidation. In addition, the effect of L-propionylcarnitine against DNA cleavage was estimated using pBR322 plasmid. We found that L-propionylcarnitine showed a dose-dependent free-radical scavenging activity. In fact, it was able to scavenge superoxide anion, to inhibit the lipoperoxidation of linoleic acid, and to protect pBR322 DNA from cleavage induced by H₂O₂ UV-photolysis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Lymphocyte subpopulations, cytokines and trace elements in asymptomatic atopic women exposed to an urban environment

This study evaluates the immune response to exposure to an urban environment from 30 non-atopic and 30 non-symptomatic women with history of respiratory and/or cutaneous allergies. Blood lymphocyte subsets and serum interleukin (IL) 4 and interferon gamma (INF-gamma) of the two groups were similar, while serum IgE and "in vitro" production of IL-4 and INF-gamma by mononuclear blood cells of the atopic women were higher spontaneously or in the presence of PHA, respectively. Blood lead of the nonatopic women (mean 55 microg/l) was positively correlated with CD4+-CD45RO-, CD3+-CD8+ and CD3--HLA-DR+ lymphocyte subsets, while urinary trans-trans muconic acid (a metabolite of benzene) of both groups of women (mean about 50 microg/l) was significantly correlated with NK CD16+CD56+ lymphocytes. Urine chromium of the non-atopic subjects was significantly correlated with activated T, B and NK HLA-DR+ cells. Urine nickel of both groups of women was correlated with CD4+-CD45RO+ "memory" lymphocytes and their ratio with CD4+-CD45RO- "virgin" lymphocytes suggesting that the metal enhances maturation of "virgin" into "memory" lymphocytes. On the whole, this study demonstrates that exposure to low levels of toxic agents, produced by vehicular traffic in an urban environment, exerts effects on immune functions of women.     

THALLUS MORPHOLOGY AND SPORE FORMATION IN CULTURED ERYTHROCLADIA IRREGULARIS ROSENVINGE (RHODOPHYTA,BANGIOPHYCIDAE)1

The discoid thallus of Erythrocladia irregularis is the result of a pattern of cellular divisions expressed by mono-and endospores; the latter are described for the first time in Erythrocladia. In nutrient enriched growth conditions the discoid thallus becomes a shapeless aggregate of unicells with a wrinkled wall surface, whose plane of division is unpredictable. The cells are able to produce monosporangia with a curved wall or they form eight-celled endosporangia. Chloroplasts have an internal pyrenoid, as is characteristic of the Erythropeltidaceae. The observation that E. irregularis can form either a colonial cluster of unicells or a discoid thallus would lead to the assignment of the genus to the Porphyridiales; however, since this order is reserved to organisms in which only the unicellular organization can be expressed, it is suggested to maintain Erythrocladia in the Erythropeltidales.     

Precision and Agreement of Corneal Power Measurements Obtained Using a New Corneal Topographer OphthaTOP

Purpose

To evaluate repeatability and reproducibility of anterior corneal power measurements obtained with a new corneal topographer OphthaTOP (Hummel AG, Germany) and agreement with measurements by a rotating Scheimpflug camera (Pentacam HR, Oculus, Germany) and an automated keratometer (IOLMaster, Carl Zeiss Meditec, Germany).

Methods

The right eyes of 79 healthy subjects were prospectively measured three times with all three devices. Another examiner performed three additional scans with the OphthaTOP in the same session. Within one week, the first examiner repeated the measurements using the OphthaTOP. The flat simulated keratometry (Kf), steep K (Ks), mean K (Km), J₀, and J₄₅ were noted. Repeatability and reproducibility of measurements were assessed by within-subject standard deviation (Sw), repeatability (2.77 Sw), coefficient of variation (CoV), and intraclass correlation coefficient (ICC). Agreement between devices was assessed using 95% limits of agreement (LoA).

Results

Intraobserver repeatability and interobserver and intersession reproducibility of all measured parameters showed a 2.77 Sw of 0.29 diopter or less, a CoV of less than 0.24%, and an ICC of more than 0.906. Statistically significant differences (P<0.001) were found between the parameters analyzed by the three devices, except J₀ and J₄₅. The mean differences between OphthaTOP and the other two devices were small, and the 95% LoA was narrow for all results.

Conclusions

The OphthaTOP showed excellent intraobserver repeatability and interobserver and intersession reproducibility of corneal power measurements. Good agreements with the other two devices in these parameters were found in healthy eyes.     

The Rules of Aggression: How Genetic,Chemical and Spatial Factors Affect Intercolony Fights in a Dominant Species,the Mediterranean Acrobat Ant Crematogaster scutellaris

Nest-mate recognition plays a key role in the biology of ants. Although individuals coming from a foreign nest are, in most cases, promptly rejected, the degree of aggressiveness towards non nest-mates may be highly variable among species and relies on genetic, chemical and environmental factors. We analyzed intraspecific relationships among neighboring colonies of the dominant Mediterranean acrobat ant Crematogaster scutellaris integrating genetic, chemical and behavioral analyses. Colony structure, parental relationships between nests, cuticular hydrocarbons profiles (CHCs) and aggressive behavior against non nest-mates were studied in 34 nests located in olive tree trunks. Bayesian clustering analysis of allelic variation at nine species-specific microsatellite DNA markers pooled nests into 14 distinct clusters, each representing a single colony, confirming a polydomous arrangement of nests in this species. A marked genetic separation among colonies was also detected, probably due to long distance dispersion of queens and males during nuptial flights. CHCs profiles varied significantly among colonies and between nests of the same colony. No relationship between CHCs profiles and genetic distances was detected. The level of aggressiveness between colonies was inversely related to chemical and spatial distance, suggesting a ‘nasty neighbor’ effect. Our findings also suggest that CHCs profiles in C. scutellaris may be linked to external environmental factors rather than genetic relationships.     

DOME/GALT type adenocarcimoma of the colon: a case report,literature review and a unified phenotypic categorization

Several types of colorectal cancers are associated with a prominent lymphoid component, which is considered a positive prognostic factor.We report a case of a dome-type carcinoma of the cecum in a 57 year old female.The sessile, non-polypoid lesion histologically consisted of a tubulovillous adenoma with low-grade dysplasia.The submucosal invasive component showed low-grade architectural features that included cystically dilated glands containing eosinohilic debris. Immunohistochemical studies displayed retention of the four mistmach repair proteins, consistent with a stable phenotype. After 3 years, the patient remains free of recurrence.A literature review highlighted striking similarities between dome-type carcinoma and the gut-associated lymphoid tissue carcinoma, the two sharing an intimate association with the gut associated lymphoid tissue.The two variants might therefore be grouped into a unified category.     

Hypertriglyceridemia Is Independently Associated with Renal,but Not Retinal Complications in Subjects with Type 2 Diabetes: A Cross-Sectional Analysis of the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study

Objective

Atherogenic dyslipidemia seems to play a major role in microvascular complications and in residual microvascular risk after statin therapy, which reduces triglycerides up to 40%. We assessed whether raised TG levels are associated with an increased burden from microvascular complications in patients with type 2 diabetes.

Methods

Subjects from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study (n=15,773) were divided in 4 groups depending on whether they had plasma triglycerides below (NTG, 67.8%) or above (HTG, 32.2%) 1.7 mmol/L and were (42.4%) or not on (57.6%) statin therapy. Estimated GFR (eGFR) was calculated from serum creatinine, albuminuria was measured by immunonephelometry or immunoturbidimetry, and retinopathy was evaluated by fundus examination.

Results

HTG subjects, either with or without statin, had higher prevalence of albuminuria, reduced eGFR and chronic kidney disease (CKD), especially the albuminuric forms, but not of retinopathy, than NTG subjects. In contrast, cardiovascular disease and advanced DR were more prevalent in subjects on statin than in those not, independently of triglyceride levels. Logistic regression analysis confirmed that HTG, without or with statin, was independently associated with micro and macroalbuminuria, mildly to severely reduced eGFR, and all CKD phenotypes, but not with retinopathy. The adjusted odd ratios for CKD increased linearly for every 0.26 mmol/L increase (approximately one decile) in triglyceride levels. The increase was higher with increasing severity of albuminuria, eGFR loss and CKD phenotype as well as in subjects receiving than in those not receiving statin treatment.

Conclusions

Triglycerides are associated with CKD, but not retinopathy in subjects with type 2 diabetes, independently of statin treatment. These data point to a possible role of hypertriglyceridemia in the development of CKD, though it remains to be demonstrated that diabetic individuals might benefit from triglyceride reduction with statins and eventually with combination therapy with fibrates.

Trial Registration

www.ClinicalTrials.gov NCT00715481     

The Changes of Lipid Metabolism in Advanced Renal Cell Carcinoma Patients Treated with Everolimus: A New Pharmacodynamic Marker?

Background

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC.

Methods

177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated.

Results

Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001). Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030), C (8 vs 5, p=0.042) and C+T raise (10.9 vs 5.0, p=0.003). At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005). T raise (21.0 vs 14.0, p=0.002) and C+T increase (21.0 vs 14.0, p=0.006) were correlated with improved OS but were not significant at multivariate analysis.

Conclusion

C+T raise is an early predictor for everolimus efficacy for patients with mRCC.