Evidence of hypolipemiant and antioxidant properties of argan oil derived from the argan tree (Argania spinosa)

BACKGROUND: Virgin argan oil is of interest in cardiovascular risk prevention due to its fat composition and antioxidant compounds. AIMS: We investigated with Moroccan subjects the effect of regular virgin argan oil consumption on lipid profile and antioxidant status and the in vitro effect of argan oil minor compounds (tocopherols, sterols and polyphenols) on LDL peroxidation. DESIGN: Healthy subjects (20 men, 76 women) were studied. Sixty-two were regular consumers of argan oil and 34 were non-consumers. METHODS: Fasting plasma lipids, antioxidant vitamins and LDL oxidation susceptibility were analyzed. In vitro LDL oxidation by phenolic and apolar compounds of virgin argan oil were performed. RESULTS: Diet composition of argan oil consumers has a higher significant content of polyunsaturated fatty acids than that of non-consumers (8.8 +/- 1.0 vs. 6.6 +/- 0.9 g, P < 0.05). Subjects consuming argan oil have lower levels of plasma LDL cholesterol (12.7%, P < 0.05) and Lp(a) (25.3%, P < 0.05) compared with the non-consumers. In argan oil consumers, plasma lipoperoxides were lower (58.3%, P < 0.01) and molar ratio alpha-tocopherol/total cholesterol (21.6%, P < 0.05) and alpha-tocopherol concentration (13.4%, P < 0.05) were higher compared with the non-consumers group. In spite of higher levels of plasma antioxidant and lower levels of lipoperoxides in argan oil consumers, LDL oxidation susceptibility remained fairly similar. A strong positive correlation was observed between increasing phenolic extract, sterol and tocopherol concentrations and the LDL-Lag phase (P < 0.05). CONCLUSIONS: Our findings suggest for the first time that regular consumption of virgin argan oil induces a lowering of LDL cholesterol and has antioxidant properties. This oil offers an additional natural food to reducing cardiovascular risk.     

Biomedical research in developing countries: the case of Morocco in the 1990s

Moroccan biomedical research occupies the third place among African or Arab countries, and its outputs considerably increased during the last decade. The quality of publications from developing countries should be improved as suggested by the comparison with developed countries. The gap between developed and developing countries is very large considering the number of publications and their quality, the number of edited journals, and the number of patented inventions, thus making developing countries more as consumers then producers. Accordingly, there is a large gap between developing and developed countries when considering the human and financial resources devoted to scientific research.     

Calcium and apoptosis: facts and hypotheses

Although longstanding experimental evidence has associated alterations of calcium homeostasis to cell death, only in the past few years the role of calcium in the signaling of apoptosis has been extensively investigated. In this review, we will summarize the current knowledge, focusing on (i) the effect of the proteins of the Bcl-2 family on ER Ca2+ levels, (ii) the action of the proteolytic enzymes of apoptosis on the Ca2+ signaling machinery, (iii) the ensuing alterations on the signaling patterns of extracellular stimuli, and (iv) the intracellular targets of 'apoptotic' Ca2+ signals, with special emphasis on the mitochondria and cytosolic Ca2+-dependent enzymes.     

c-Jun NH2-terminal kinase-mediated signaling is essential for Pseudomonas aeruginosa ExoS-induced apoptosis

As an opportunistic bacterial pathogen, Pseudomonas aeruginosa mainly affects immunocompromised individuals as well as patients with cystic fibrosis. In a previous study, we showed that ExoS of P. aeruginosa, when injected into host cells through a type III secretion apparatus, functions as an effector molecule to trigger apoptosis in various tissue culture cells. Here, we show that injection of the ExoS into HeLa cells activates c-Jun NH(2)-terminal kinase (JNK) phosphorylation while shutting down ERK1/2 and p38 phosphorylation. Inhibiting JNK activation by expression of a dominant negative JNK1 or with a specific JNK inhibitor abolishes ExoS-triggered apoptosis, demonstrating the requirement for JNK-mediated signaling. Following JNK phosphorylation, cytochrome c is released into the cytosol, leading to the activation of caspase 9 and eventually caspase 3. Although c-Jun phosphorylation is also observed as a result of JNK activation, ongoing host protein synthesis is not essential for the apoptotic induction, suggesting that c-Jun- or other AP-1-driven activation of gene expression is dispensable in this process. Therefore, ExoS has opposing effects on different cellular pathways that regulate apoptosis: it shuts down host cell survival signal pathways by inhibiting ERK1/2 and p38 activation, and it activates proapoptotic pathways through activation of JNK1/2 leading ultimately to cytochrome c release and activation of caspases. These results highlight the modulation of host cell signaling by the type III secretion system during interaction between P. aeruginosa and host cells.     

Intestinal surgery with activated recombinant factor VII prophylaxis in patients with haemophilia A and high responding inhibitors: a report of five cases.

Five patients with severe haemophilia A and high responding inhibitors underwent laparoscopic or open surgery on the digestive tract (appendicectomy, cholecystectomy, partial colectomy, or haemorrhoidectomy) with recombinant activated factor VII (rFVIIa) prophylaxis. rFVIIa was administered at a dose of 92-127 mug/kg prior to surgery and then every 2 h for 18-56 h before increasing the dosing interval. One patient was switched to a continuous infusion after 48 h of rFVIIa boluses. rFVIIa treatment lasted between 5 and 14 days in four patients, with good or excellent efficacy (total dose, 3.13-9.28 mg/kg). The fifth patient, who underwent surgery for prolapsed haemorrhoids, bled on day 6 and day 10 after the procedure, despite a satisfactory prothrombin time and factor VII coagulant level. The rFVIIa dose regimen was increased after the second bleeding episode, then the bleeding rapidly ceased after this modification to the treatment regimen. The total dose of rFVIIa used was 12.65 mg/kg, and treatment lasted 17 days. Antifibrinolytic treatment was used concomitantly in all five patients. Clinical and biological tolerability was excellent, and no increase in the anti-factor VIII inhibitor titre was observed. These results suggest that rFVIIa prophylaxis is effective in haemophilia A patients with factor VIII inhibitors who are undergoing elective or emergency intestinal surgery. Further studies are required to optimize the dose regimen and treatment period according to the surgical indication and technique.     

Testing independence between two Poisson-generated multinomial variables in case-series and cohort studies

In case-series or cohort studies, we propose a test of independence between the occurrences of two types of recurrent events (such as two repeated infections) related to an intermittent exposure (such as an antibiotic treatment). The test relies upon an extension of a recent method for analysing case-series data, in the presence of one type of recurrent event. The test statistic is derived from a bivariate Poisson generated-multinomial distribution. Simulations for checking the validity of the test concerning the type I error and the power properties are presented. The test is illustrated using data from a cohort on antibiotics bacterial resistance in schoolchildren.     

Reciprocal regulation of agonist and inverse agonist signaling efficacy upon short-term treatment of the human delta-opioid receptor with an inverse agonist

Rapid regulation of receptor signaling by agonist ligands is widely accepted, whereas short-term adaptation to inverse agonists has been little documented. In the present study, guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding and cAMP accumulation assays were used to assess the consequences of 30-min exposure to the inverse agonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI174864) (1 microM) on delta-opioid receptor signaling efficacy. ICI174864 pretreatment increased maximal effect (E(max)) for the partial agonist Tyr-1,2,3,4-tetrahydroisoquinoline-Phe-Phe-OH (TIPP) at the two levels of the signaling cascade, whereas E(max) values for more efficacious agonists like (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80) and bremazocine were increased in [(35)S]GTPgammaS binding but not in cAMP accumulation assays. Pre-exposure to ICI174864 also induced a shift to the left in dose-response curves for bremazocine and TIPP. On the other hand, E(max) for the inverse agonist H-Tyr-TicPsi[CH(2)NH]Cha-Phe-OH was reduced in both assays, but no changes in potency were observed. For the weaker inverse agonist naloxone, E(max) in [(35)S]GTPgammaS binding was drastically modified because the drug turned from inverse agonist to agonist after ICI174864 pretreatment. Likewise, ICI174864 turned from inverse agonist to agonist when tested in cAMP accumulation assays. In both cases, inversion of efficacy was concomitant with marked increase in potency for agonist effects. Together with functional changes, short-term treatment with ICI174864 reduced basal receptor phosphorylation and increased immunoreactivity for Galpha(i3) in membrane preparations. Functional consequences of ICI174864 pretreatment were simulated in the cubic ternary complex model by increasing receptor/G protein coupling or G protein amount available for interaction with the receptor. Taken together, these data show that inverse agonists may induce rapid regulation in receptor signaling efficacy.     

Multiple evidence for nucleotide metabolism in the chloroplast thylakoid lumen

The apparatus of photosynthetic energy conversion in chloroplasts is quite well characterized with respect to structure and function. Light-driven electron transport in the thylakoid membrane is coupled to synthesis of ATP, used to drive energy-dependent metabolic processes in the stroma and the outer surface of the thylakoid membrane. The role of the inner (luminal) compartment of the thylakoids has, however, remained largely unknown although recent proteomic analyses have revealed the presence of up to 80 different proteins. Further, there are no reports concerning the presence of nucleotides in the thylakoid lumen. Here, we bring three lines of experimental evidence for nucleotide-dependent processes in this chloroplast compartment. (i) The thylakoid lumen contains a protein of 17.2 kDa, catalyzing the transfer of the gamma-phosphate group from ATP to GDP, proposed to correspond to the nucleoside diphosphate kinase III. (ii) The 33-kDa subunit of photosystem II, bound to the luminal side of the thylakoid membrane and associated with the water-splitting process, can bind GTP. (iii) The thylakoid membrane contains a nucleotide transport system that is suggested to be associated with a 36.5-kDa nucleotide-binding protein. Our results imply, against current dogmas, that the thylakoid lumen contains nucleotides, thereby providing unexpected aspects on this chloroplast compartment from a metabolic and regulatory perspective and expanding its functional significance beyond a pure bioenergetic function.