Carnitine inhibits arachidonic acid turnover,platelet function,and oxidative stress

Carnitine is a physiological cellular constituent that favors intracellular fatty acid transport, whose role on platelet function and O(2) free radicals has not been fully investigated. The aim of this study was to seek whether carnitine interferes with arachidonic acid metabolism and platelet function. Carnitine (10-50 microM) was able to dose dependently inhibit arachidonic acid incorporation into platelet phospholipids and agonist-induced arachidonic acid release. Incubation of platelets with carnitine dose dependently inhibited collagen-induced platelet aggregation, thromboxane A(2) formation, and Ca(2+) mobilization, without affecting phospholipase A(2) activation. Furthermore, carnitine inhibited platelet superoxide anion (O(2)(-)) formation elicited by arachidonic acid and collagen. To explore the underlying mechanism, arachidonic acid-stimulated platelets were incubated with NADPH. This study showed an enhanced platelet O(2)(-) formation, suggesting a role for NADPH oxidase in arachidonic acid-mediated platelet O(2)(-) production. Incubation of platelets with carnitine significantly reduced arachidonic acid-mediated NADPH oxidase activation. Moreover, the activation of protein kinase C was inhibited by 50 microM carnitine. This study shows that carnitine inhibits arachidonic acid accumulation into platelet phospholipids and in turn platelet function and arachidonic acid release elicited by platelet agonists.     

Lipido‐sterolic extract of Serenoa repens (LSESr,Permixon®) treatment affects human prostate cancer cell membrane organization

The molecular mechanism by which the lipido‐sterolic extract of Serenoa repens (LSESr, Permixon®) affects prostate cells remains to be fully elucidated. In androgen‐independent PC3 prostate cancer cells, the LSESr‐induced effects on proliferation and apoptosis were evaluated by counting cells and using a FACScan cytofluorimeter. PC3 cells were stained with JC‐1 dye to detect mitochondrial membrane potential. Cell membrane lipid composition was evaluated by thin layer chromatography and gas chromatographic analysis. Akt phosphorylation was analyzed by Western blotting and cellular ultrastructure through electron microscopy. LSESr (12.5 and 25 µg/ml) administration exerted a biphasic action by both inhibiting proliferation and stimulating apoptosis. After 1 h, it caused a marked reduction in the mitochondrial potential, decreased cholesterol content and modified phospholipid composition. A decrease in phosphatidylinositol‐4,5‐bisphosphate (PIP2) level was coupled with reduced Akt phosphorylation. After 24 h, all of these effects were restored to pre‐treatment conditions; however, the saturated (SFA)/unsaturated fatty acid (UFA) ratio increased, mainly due to a significant decrease in ω6 content. The reduction in cholesterol content could be responsible for both membrane raft disruption and redistribution of signaling complexes, allowing for a decrease of PIP2 levels, reduction of Akt phosphorylation and apoptosis induction. The decrease in ω6 content appears to be responsible for the prolonged and more consistent increase in the apoptosis rate and inhibition of proliferation observed after 2–3 days of LSESr treatment. In conclusion, LSESr administration results in complex changes in cell membrane organization and fluidity of prostate cancer cells that have progressed to hormone‐independent status. J. Cell. Physiol. 219: 69–76, 2009. © 2008 Wiley‐Liss, Inc.     

Hospital Admissions for Hypertensive Crisis in the Emergency Departments: A Large Multicenter Italian Study

Epidemiological data on the impact of hypertensive crises (emergencies and urgencies) on referral to the Emergency Departments (EDs) are lacking, in spite of the evidence that they may be life-threatening conditions. We performed a multicenter study to identify all patients aged 18 years and over who were admitted to 10 Italian EDs during 2009 for hypertensive crises (systolic blood pressure ≥220 mmHg and/or diastolic blood pressure ≥120 mmHg). We classified patients as affected by either hypertensive emergencies or hypertensive urgencies depending on the presence or the absence of progressive target organ damage, respectively. Logistic regression analysis was then performed to assess variables independently associated with hypertensive emergencies with respect to hypertensive urgencies. Of 333,407 patients admitted to the EDs over the one-year period, 1,546 had hypertensive crises (4.6/1,000, 95% CI 4.4–4.9), and 23% of them had unknown hypertension. Hypertensive emergencies (n = 391, 25.3% of hypertensive crises) were acute pulmonary edema (30.9%), stroke (22.0%,), myocardial infarction (17.9%), acute aortic dissection (7.9%), acute renal failure (5.9%) and hypertensive encephalopathy (4.9%). Men had higher frequency than women of unknown hypertension (27.9% vs 18.5%, p<0.001). Even among known hypertensive patients, a larger proportion of men than women reported not taking anti-hypertensive drug (12.6% among men and 9.4% among women (p<0.001). Compared to women of similar age, men had higher likelihood of having hypertensive emergencies than urgencies (OR = 1.34, 95% CI 1.06–1.70), independently of presenting symptoms, creatinine, smoking habit and known hypertension. This study shows that hypertensive crises involved almost 5 out of 1,000 patients-year admitted to EDs. Sex differences in frequencies of unknown hypertension, compliance to treatment and risk of hypertensive emergencies might have implications for public health programs.     

Scent-deposition Behaviour in Alpine Marmots (Marmota marmota L.): its Role in Territorial Defence and Social Communication

Scent-deposition was investigated in Marmota marmota L. at Gran Paradiso National Park. 448 h of focal and scan sampling were performed on 22 marmots in four subsequent years. Results show that: (1) 97.4 % of the scent-deposition is done within 25 m of the edge of the territories or of the main burrows (X² = 100.4, df 9, p < 0.001); (2) being a reproducing adult is the most prominent factor in scent-deposition (X² = 32.4, df = 18, p < 0.002). The role of factors affecting scent-deposition in territorial defence and social communication is discussed.     

Comparative macroscopic and microscopic anatomical observations on pyloric ceca in some bony fish

The authors report the variable number of pyloric caeca of some species of fish and describe their macroanatomy. They also describe and compare the microanatomy of pyloric caeca in three species; in particular they point out the thickness of tunica muscularis, the shape and length of villi which protrude into the lumen and the variable number of goblet cells. The tunica muscularis is very strong in Uranoscopus and consists of three strata: external and inner longitudinal strata, middle circular stratum. The tunica muscularis is less thick in Diplodus and in Scorpaena. The lamina propria and epithelium form villi which protrude into the lumen. They are covered with columnar epithelium and goblet cells which are more numerous in Uranoscopus and Scorpaena and less numerous in Diplodus. At last the authors describe in pyloric caeca of Scorpaena the presence of a network which engages all the lumen; it consists of connective tissue septa which directly derive from the lamina propria and is covered with the same columnar epithelium and goblet cells.     

Further observations and considerations on the biological and reproductive cycle of the roe buck (Capreolus capreolus L.)

The authors have studied the seasonal microanatomical modifications of the ovary of the roe deer and testis of the roe buck. The ovary during the month of September presents primary, secondary and mature vesicular follicles. During the month of October there is the first presence of a corpus luteum. The corpora lutea during the months of November and December increase in size and blood supply; the cells are filled with acidophil granules. The corpora lutea persist also in January and February when embryos are implanted in the uterus. This result agrees with Short's and -Hay's but differs from that of Stieve. Testes show the first spermatogenic activity during the month of April. The spermatogenesis is completed in June, persists and reaches the top during July and August, when the Leydig cells acquire a strong acidophil cytoplasm. Indeed the spermatogenesis decreases during September and October; then, during winter months the testes are devoid of all signs of spermatogenic activity, the tubules being lined only be Sertoli cells and spermatogonia.     

Research in experimental electrocardiography. I: action of DCA-ajmaline on the electrocardiogram of the rat

In the course of their experiments, the Authors did not observe any modifications in the rat electrocardiogram, induced by a 2,5 mg DCA-ajmaline intravenous injection, nor, in particular, any negative bathmotropic action due to it.     

Vitamin C inhibits platelet expression of CD40 ligand

Upon stimulation with agonists, platelets express CD40 ligand (CD40L), a transmembrane protein implicated in the initiation and progression of atherosclerotic disease. We have recently discovered that oxidative stress plays a major role in platelet CD40L expression. In this study, we sought to determine whether vitamin C, a known antioxidant, is able to influence platelet CD40L expression. In vitro experiments were done by stimulating platelets with collagen in the presence or absence of vitamin C (50–100 μM) or vehicle as control. An in vivo study was done in 10 healthy subjects who were randomized to intravenous infusion of placebo or 1 g vitamin C for 45 min in a crossover design. At the end of infusion platelet CD40L and O_2- were measured. The in vitro study demonstrated that vitamin C dose dependently inhibited platelet CD40L expression without affecting agonist-induced platelet aggregation. In subjects treated with placebo no changes of platelet CD40L and O_2- were observed; conversely, vitamin C infusion caused a significant and parallel decrease of platelet O_2- (−70%, P < 0.001) and CD40L (−68%, P < 0.001). Platelet aggregation was not modified by either treatment. This study suggests that water-soluble antioxidants, which scavenge superoxide radicals, may reduce platelet CD40L expression.