Design and production of methyl jasmonate nanoemulsions using experimental design technique and evaluation of its anti-cancer efficacy.

Methyl jasmonate (MJ), a plant-derived stress hormone, has been shown to be a promising anti-cancer agent with high selectivity toward cancerous cells. The aim of the present study was to design a MJ loaded nanoemulsion (NE) to overcome the low MJ water solubility and also improve its anti-cancer efficiency. Box-Behnken design (BBD) was employed to optimize the composition effect of three independent manufacturing variables on two responses including average droplet size and poly dispersity index (PDI). ANOVA analysis indicated that both of the studied responses were well fitted by resultant quadratic models with the coefficient of determinations (R2) 0.994 and 0.975, respectively. The actual average droplet size 75.06 nm and PDI 0.017 obtained for the optimum MJNE was in good agreement with those values predicted with numerical optimization. Physicochemical characterization indicated that the optimum MJNE was transparent, isotropic, spherical and sterically stabilized. MTT assay indicated that MJNE was more efficacious in killing cancer cells than MJ solution. Cell cycle analysis revealed that MJNE induced a stronger sub-G1 arrest than MJ solution. A considerable absence of toxicity was achieved for MJNE and blank NE in HUVEC normal cells. These results may provide strong support to develop a NE delivery system as a promising carrier for improving the safety and anti-cancer efficacy of MJ.

Modulation of the hepatocyte rough endoplasmic reticulum single chloride channel by nucleotide-Mg2+ interaction.

The effect of nucleotides on single chloride channels derived from rat hepatocyte rough endoplasmic reticulum vesicles incorporated into bilayer lipid membrane was investigated. The single chloride channel currents were measured in 200/50 mmol/l KCl cis/trans solutions. Adding 2.5 mM adenosine triphosphate (ATP) and adenosine diphosphate (ADP) did not influence channel activity. However, MgATP addition inhibited the chloride channels by decreasing the channel open probability (Po) and current amplitude, whereas mixture of Mg(2+) and ADP activated the chloride channel by increasing the Po and unitary current amplitude. According to the results, there is a novel regulation mechanism for rough endoplasmic reticulum (RER) Cl(-) channel activity by intracellular MgATP and mixture of Mg(2+) and ADP that would result in significant inhibition by MgATP and activation by mixture of Mg(2+) and ADP. These modulatory effects of nucleotide-Mg(2+) complexes on chloride channels may be dependent on their chemical structure configuration. It seems that Mg-nucleotide-ion channel interactions are involved to produce a regulatory response for RER chloride channels.

Oxyntomodulin reduces expression of glucagon-like peptide 1 receptor in the brainstem of chickens.

Oxyntomodulin (OXM) is a peptide released from the gut and attenuates food intake by acting on hypothalamus. However, its role at the molecular level is not well studied. In the first section of this study, we analysed the effect of OXM on food intake behaviour after injecting into the lateral ventricle of chickens. The outcome showed that food intake decreased significantly after administering 4 nmol of OXM. In the second part, the expression of glucagon-like peptide 1 receptor (GLP-1R) in the brainstem was analysed by real-time RT-PCR. The results showed that expression of GLP-1R was reduced to 27% and 16% at 30 and 90 mins after injection of OXM respectively. In saline-injected chickens, no reduction in GLP-1R was seen. It can be concluded that OXM has a down regulatory effect on the responding receptor, GLP-1R and OXM in chicks has the same reductive effect on food intake as in the mammals.

Effects of salinity on survival, growth, reproductive and life span characteristics of Artemia populations from Urmia Lake and neighboring lagoons.

This study deals with effects of different salinities on the survival, growth, reproductive and lifespan characteristics of three Artemia populations from Urmia Lake and small lagoons at the vicinity of the lake under laboratory conditions. Experimental salinities ranged from 75 to 175 g L(-1). Salinity was proved to have significant impact on the majority of the characters studied in this survey. Growth and survival in bisexual A. urmiana and parthenogenetic Artemia from Lake Urmia were significantly higher with respect to the parthenogenetic Artemia from lagoons at most of the salinities tested. Reproductive characteristics such as total number of broods, total offspring number of offspring in each brood and number of offspring at each day of reproductive period reduced with increasing salinity. Moreover higher salinity prolonged the prereproductive period but shortened the total reproductive period. Higher salinities also affected the percentage of encystment and post-reproductive period, showing significantly higher values in parthenogenetic populations in comparison to bisexual A. urmiana.

Effect of mono-(2-ethylhexyl) phthalate (MEHP) on resumption of meiosis, in vitro maturation and embryo development of immature mouse oocytes.

The purpose of this study was to evaluate the effect of MEHP on in vitro maturation of mouse oocytes and resulting embryo development. Denuded oocytes (DO) were cultured in maturation medium supplemented with 0, 50, 100, 200 and 400 microM levels of MEHP for 24 h. The matured oocytes then were fertilized and cultured for 4 days. The percentage of Germinal Vesicle (GV) stage oocytes were significantly higher in 200 and 400 microM MEHP treatment comparing to the control (P < 0.05). The proportion of oocytes that progressed to the metaphase II (MII) stage was significantly decreased by adding of MEHP in a dose related pattern. The 2-cell embryo formation was significantly decreased with 400 microM treatments than the control. Moreover with further culture in experimental groups none of the embryos comparing to that of the control group were developed to morulla stage (P < 0.05). These results indicate that MEHP could negatively modulate mouse oocyte meiotic maturation in vitro and embryo development, suggesting possible risks for human and other mammalians reproductive health.

Involvement of nucleus accumbens in L-arginine-induced conditioned place preference in rats.

In the present study, the effects of intraperitoneal, intra-accumbal and intra-ventral tegmental area administration of L-arginine and N(G)-nitro-L-arginine methyl-ester (L-NAME) on conditioned place preference behavior were studied. Intraperitoneal (i.p.; 0.5, 1 and 5 mg/kg) and intra-accumbal (intra-NAc; 0.3, 1 and 3 microg/rat), but not intra-ventral tegmental area (intra-VTA; 0.3, 1 and 3 microg/rat) administrations of L-arginine produced a significant place conditioning. Similar injections of L-NAME did not produce any response. However, intraperitoneal pretreatment of the animals with L-NAME (5, 10 and 20 mg/kg), 30 min before L-arginine administration, significantly abolished the acquisition of place conditioning induced by either intraperitoneal or intra-accumbal injection of L-arginine. Moreover, injection of L-NAME (5, 10 and 20 mg/kg) on the test day did not alter the L-arginine response. The results may indicate that L-arginine induces conditioned place preference via an increase in nitric oxide (NO) in the nucleus accumbens.

[Chromosomal studies of male infertility]. / Khromosomnoe issledovanie muzhskogo besplodiia.

Prometaphase and metaphase chromosome analyses performed on 70 consecutive men with primary infertility (for a period of at least 2 years) revealed 8 (11.42%) men with some kind of chromosomal abnormality. The highest frequency of abnormal karyotypes (10%) was found among patients with azpospennia and the most frequent anomaly was 47, XXY chromosomal constitution, found in 6 (8.57%) patients. All the chromosomal aberrations found in this study was sex chromosomal type and we did not find any autosomal aberration. All patients with numerical chromosomal anomalies had azoospermia. The incidence of structural aberration in our study was 1.42%. Fifteen patients had different chromosomal variants (21.38%). We suggest that men with azoospermia should be considered for cytogenetic investigation and we report that "variants of the Y chromosome" have no influence on the sperm count (million/ml) and fertility of men.

Synthesis and calcium channel antagonist activity of nifedipine analogues with methylthioimidazole substituent.

Various diester analogues of nifedipine, in which the orthonitrophenyl group at position 4 is replaced by 1-methyl-2-methylthio-5-imidazolyl substituent, were synthesized and evaluated as calcium channel antagonists on guinea-pig ileal smooth muscle. Nifedipine was used as standard. Comparison of the activities of symmetrical esters (3a-e) indicate that increasing the length of alkyl chain in C3 and C5 ester substituents increases the antagonist activity and the n-propyl ester being preferred (IC50= 2.66 x 10(-9) M). In asymmetrical series (6a-g), compound 6g having ethyl and n-butyl ester at C3 and C5 positions of basic dihydropyridine structure was found to be the most active (IC50= 1.32 x 10(-9) M).

Chromosomal studies in infertile men.

Prometaphase and metaphase chromosome analyses performed on 70 consecutive men with primary infertility (for a period of at least 2 years) revealed 8 (11.42%) men with some kind of chromosomal abnormality. The highest frequency of abnormal karyotypes (10%) was found among patients with azoospermia and the most frequent anomaly was 47, XXY chromosomal constitution, found in 6 (8.57%) patients. All the chromosomal aberrations found in this study, was sex chromosomal type and we did not find any autosomal aberration. All patients with numerical chromosomal anomalies had azoospermia. The incidence of structural aberration in our study was 1.42%. 15 patients had different chromosomal variants (21.38%). We suggest that men with azoospermia should be considered for cytogenetic investigation and we report that "variants of the Y chromosome" have no influence on the sperm count (Million/ml) and fertility of men.

Quantification of C3 and C4 in infertile men with antisperm antibody in their seminal plasma.

PROBLEM: Previous studies showed that some infertilities are caused by antisperm antibodies (ASAs). It was shown that some major complement (C) components are present in seminal fluid. Due to the role of C in the pathogenesis of ASAs, the existence and amount of two key C components (C3 and C4) were investigated in seminal plasma (SP). METHOD OF STUDY: Single radial immunodiffusion assay and a sandwich-type enzyme-linked immunosorbent assay (ELISA) were used for C3 and/or C4 quantification, respectively, in serum and SP, and the tray agglutination test was used for ASA detection in 12 fertile and 53 infertile men (18 ASA-positive [ASA+] and 35 ASA-negative [ASA-] men). RESULTS: Of the 18 ASA + infertile men, 61.11% had positive C3, whereas 27.77% showed positive C4 levels. ASA + infertile men showed significant differences in seminal plasma C3 mean values compared with ASA- infertile (P < 0.01) and fertile (P < 0.05) men, but the seminal plasma C4 values only showed differences compared with ASA- infertile men (P < 0.05). No significant differences were observed in serum C3 and/or C4 levels of ASA+ infertile men compared with other groups. No significant correlation was found between ASA titer and C3 and C4 levels in SP. A significant correlation existed between SP and serum C3 levels of ASA+ (r = 0.522, P < 0.01) and ASA- (r = 0.451, P < 0.01) infertile men, but no correlation was observed between C4 levels. CONCLUSIONS: In the presence of ASAs, the C system has no definitive activity in blood serum or outside the male genital tract. In SP, and in association with ASAs, C has no lytic activity by the classical pathway. The excess of C3 in SP of ASA+ infertile men may participate in other C-mediated activities in the male reproductive tract.

Oral administration of pectin-rich plant extract enhances C3 and C4 complement concentration in woman colostrum.

C3 and C4 components of the complement are normally present in human colostrum. These compounds are natural antibacterial agents. Pectin-rich plant extracts have been shown to induce prolactin release and milk synthesis when administered by the oral route in rat. In the present work, extract from a plant rich in pectin, Gossypium herbaceum was given orally to women 2 days after parturition. The extract enhanced concentration of C3 and C4 in colostrum but did not modify the total hemolytic complement activity (TCH50). No change in the concentration of the three compounds was observed in serum of the treated women. Control experiments showed that a treatment by placebo had no effect on colostrum composition. These data suggest that pectin-rich plant extracts favour transfer of C3 and C4 from blood to colostrum by an unknown mechanism. This observation suggests that some plant extracts might be used to reinforce the antibacterial activity of human colostrum.

Beta-glucan and pectin derivatives stimulate prolactin secretion from hypophysis in vitro.

Previous work has shown that various plant extracts administered to animals stimulate milk protein synthesis through the secretion of prolactin. It has also been shown that beta-glucan and pectin are the active molecules capable of stimulating prolactin release in vivo after intravenous injections. In this work, it is shown that beta-glucan and several pectin derivatives are able to stimulate prolactin secretion from hypophysis fragments incubated for 2 hr in a synthetic medium.

[Evidence for a stimulating factor of prolactin and growth hormone secretion present in brewery draff]. / Mise en évidence d'un facteur stimulant la sécrétion de prolactine et de l'hormone de croissance dans les drèches de brasserie.

Aquous extracts of brewery draff injected intravenously into ewes and cows induced prolactin and growth hormone (GH) secretion. The same draff added to the feed of cows appeared to be unable to significantly stimulate the blood level of prolactin and GH. In these experimental conditions, milk production was not enhanced by draff. Pure beta-glucan extracted from barley also stimulated hormone secretion when administered by the intravenous route. Barley, bier and draff therefore contain a beta-glucan-like factor which stimulates lactogenic hormone secretion. The amount present in draff is probably unable to cause an increase in hormones when administered orally. Hence, the well-established stimulatory effect of draff on milk production results from their nutritive value rather than from their ability of modulating the endocrine system.

[The effect of pregnant mare's serum on the level of K+ ions in the immature rat ovary]. / Action d'une gonadotrophine sérique sur la teneur en ions K+ de l'ovaire de ratte impubère

Pregnant Mare Serum Gonadotrophin enhanced potassium level in immature rat ovaries in comparison with controls, three hours after intravenous injection. In vivo 42K uptake was also 36% higher (p less than or equal to 0,01) in PMSG primed rat ovaries. This response was specific to the ovary. Experiments are carried out to determine correlation between K+ level and macromolecule biosynthesis.