Organotin derivatives of cholic acid induce apoptosis into breast cancer cells and interfere with mitochondrion; Synthesis, characterization and biological evaluation.

Organotin(IV) derivatives of cholic acid (CAH) with the formulae R3Sn(CA) (R = Ph- (1), n-Bu- (2)) and R2Sn(CA)2 (R = Ph- (3), n-Bu- (4) and Me- (5)) were synthesized. The compounds were characterized in solid state by melting point, FT-IR, 119Sn Mössbauer, X-ray fluorescence (XRF) spectroscopy and in solution by 1H NMR, UV-Vis spectral data and by Electrospray Ionisation Mass spectrometry (ESI-MS), High Resolution Mass spectrometry (HRMS), and atomic absorption analysis. The in vitro bioactivity of 1-5 against human breast adenocarcinoma cancer cells MCF-7 (positive to hormone receptors) and MDA-MB-231 (negative to hormone receptors) reveal that triorganotin derivatives 1-2 exhibit significantly stronger activity than the corresponding diorganotin ones. Compound 5 is inactive against both cell lines at the concentrations tested. Triorganotins 1-2 inhibit selectively MCF-7 than MDA-MB-231 cells, suggesting hormone mimetic behavior of them. Organotins 1-4 inhibit both cancerous cell lines, stronger than cisplatin which rise up to 55-fold against MCF-7 and 170-fold against MDA-MB-231. The in vitro toxicity of 1-4 was evaluated on normal human fetal lung fibroblast cells (MRC-5), while their genotoxicity in vitro by micronucleus assay (MN). Moreover, the in vivo toxicity of 1-4 was tested by Artemia salina assay and their in vivo genotoxicity with Allium cepa test. The mechanism of action of 1-4 against MCF-7 was clarified in vitro by the means of cell morphology studies, cell cycle arrest, Acridine Orange/Ethidium Bromide (AO/EB) Staining, mitochondrial membrane permeabilization test and by their binding affinity toward the calf thymus (CT) DNA.

Innovative material containing the natural product curcumin, with enhanced antimicrobial properties for active packaging.

Curcumin (Curc) reacts with zinc di­iodine (ZnI2) in 2:1molar ratio in the presence of an excess of a base triethylamine ((CH3CH2)3N) in methanol (CH3OH) solution towards the amorphous solid material of formula [ZnI2(Curc)2] (1). The complex was characterized by melting point (m.p.), Fourier Transform-Infra Red (FT-IR) and Nuclear Magnetic Resonance of hydrogen nucleus (1H NMR) spectroscopy. The formula of 1 was determined by X-ray fluorescence (XRF) analysis. The retention of the structure in solution was confirmed by 1H NMR spectroscopy. The antimicrobial activity of the complex has been studied against the bacteria Pseudomonas aeruginosa (PAO1). The Minimum Inhibitory Concentrations (MIC) of the compounds 1 and Curc against P. aeruginosa (PAO1) are: 71.3µΜ (75.3µg/mL) for [ZnI2(Curc)2] and 339µM (125µg/mL) for Curc, respectively. Moreover, the antimicrobial activity of the new material which was diffused in polystyrene against biofilm formed by PAO1 was also calculated.

Effect of LSR polymorphism on blood lipid levels and age-specific epistatic interaction with the APOE common polymorphism.

The lipolysis stimulated lipoprotein receptor (LSR) is an apolipoprotein (Apo) B and ApoE receptor that participates in the removal of triglyceride-rich lipoproteins during the postprandial phase. LSR gene is located upstream of APOE, an important risk factor for cardiovascular disease (CVD). Since the APOE common polymorphism significantly affects the variability of lipid metabolism, this study aimed to determine the potential impact of a functional SNP rs916147 in LSR gene on lipid traits in healthy subjects and to investigate potential epistatic interaction between LSR and APOE. Unrelated healthy adults (N = 432) and children (N = 328, <18 years old) from the STANISLAS Family Study were used. Age-specific epistasis was observed between APOE and LSR, reversing the protective effect of APOE ε2 allele on cholesterol, ApoE and low-density lipoprotein levels (ß: .114, P: .777 × 10-8 , ß: .125, P: .639 × 10-3 , ß: .059, P: .531 × 10-3 , respectively). This interaction was verified in an independent adult population (n = 1744). These results highlight the importance of the LSR polymorphism and reveal the existence of complex molecular links between LSR and ApoE for the regulation of lipid levels, revealing potential new pathways of interest in type III hyperlipidemia and its involvement in CVD pathology.

IL6R haplotype rs4845625*T/rs4537545*C is a risk factor for simultaneously high CRP, LDL and ApoB levels.

Interleukin 6 receptor (IL-6R), mediating IL-6's biological functions, plays an important role in different diseases such as diabetes, obesity and cardio-vascular diseases. In this study, we investigated the effects of two single nucleotide polymorphisms (SNPs), within the IL-6R loci, previously associated with C-reactive protein (CRP) and coronary heart diseases risk, and with controversial effects on lipids traits: SNP rs4845625 and SNP rs4537545. The results showed that both investigated SNPs were antagonistically related with CRP levels; the minor rs4845625*T allele was associated with increased CRP levels (P-value=0.011), while the minor rs4537545*T allele was associated with decreased CRP levels (P-value=0.009). Interestingly, the minor rs4845625*T allele was significantly associated with higher low-density lipoprotein cholesterol (LDL-C) and ApoB levels (P=0.007 and P=0.009 respectively). Haplotype analysis showed that the TC haplotype, having the minor rs4845625*T allele, was related simultaneously with increased levels of CRP, LDL-C and ApoB levels, thus could be considered as a risk factor. Our investigation detects for the first time an independent effect of rs4845625 on LDL-C and ApoB traits, explaining an important range of those traits variability (3.49 and 5.57% respectively). Our findings might be of high clinical significance in pharmacogenomics studies of tocilizumab for which IL-6R is target.

VEGF-related polymorphisms identified by GWAS and risk for major depression.

Depression is a common, severe, disabling mental disease that affects millions of people of all ages worldwide. Various studies have shown that neurotrophic/growth factors have a key role in depression and, more specifically, vascular endothelial growth factor (VEGF) is implicated in the pathogenesis of depression. The purpose of this study was to investigate the potential links between four VEGF-related single-nucleotide polymorphisms (SNPs), previously identified through a genome-wide association study (GWAS) and depression. The direct effects and epistatic interactions of the four VEGF-related SNPs (rs10738760, rs6921438, rs6993770 and rs4416670) on depression were investigated through a case-control study including 437 individuals diagnosed with depression and 477 healthy volunteers as controls. Gender, age and body mass index influence was additionally analyzed. The SNP rs4416670 was associated with increased risk for depression (OR: 1.60, P: 0.010). This result demonstrates the existence of relationships between VEGF genetic determinants and depression. This novel association reveals new molecular mechanisms suggesting the potential role of VEGF in depression development that could help to promote a personalized prediction for this severe common disease.

A double-blind, randomized clinical trial of the effect of omega-3 fatty acids on the oxidative stress of preterm neonates fed through parenteral nutrition.

BACKGROUND/OBJECTIVES: The aim of this study was to research and draw conclusions about the effect of a parenteral nutrition (PN) fat emulsion, rich in omega-3 fatty acids, on the antioxidant markers of preterm infants, when compared with a standard fat emulsion. This was a double-blind, parallel-group study conducted in Athens, Greece, using an equal randomization method. SUBJECTS/METHODS: Thirty-eight infants were selected using a double-blind method and a computer-generated randomization list. Both groups received PN, based on the same protocols. Group A received SMOFlipid fat emulsion, while group B received the standard fat emulsion (Intralipid). Serum levels of vitamin A, E and total antioxidant potential (TAP) were measured on days 0, 7 and 14 of PN support. Clinical and biochemical data were collected on days 0, 14 and on the day of discharge. RESULTS: Serum levels of vitamin E and A were significantly increased in group A, while only vitamin A serum level was increased in group B on the fourteenth day (group A: vitamin E: P-value=0.002, vitamin A: P-value=0.000, group B: vitamin E: P-value=0.065, vitamin A: P-value=0.000). TAP was increased only in the intervention group (group A: P-value=0.000, group B: P-value=0.287). Mild anemia was developed in both groups, while no differences were detected in the infection rate, days of hospitalization, days of ventilator support and days of phototherapy. CONCLUSIONS: Oxidative stress was significantly reduced in those neonates fed with omega-3 fatty acids, whereas no effect was observed in the neonates fed with standard lipids. Intervention had no effect on infants' growth and clinical outcome.

Lack of association between vitamin D and calcitonin receptor gene polymorphisms and forearm bone values of young Greek males.

UNLABELLED: INTRODUCTION--HYPOTHESIS: Since the genetic bases of bone mass regulation in males are still poorly understood and the role of calciotropic hormones on bone mineral metabolism is absolute, our hypothesis is based on the certainty that specific genetic polymorphism will contribute, at least, on bone mass values. Our objective was to examine the relative contribution of genetic variables to the regulation of bone values in a population of young healthy men, focusing on the BsmI polymorphism of vitamin D receptor (VDR) gene and the AluI polymorphism of calcitonin receptor (CTR) gene. METHODS: Areal bone mineral density (aBMD), bone mineral content (BMC) and geometrical areas at specific skeletal sites of the forearm, of 301 healthy Caucasian young men, aged 18-25, were assessed by single X-ray absorptiometry (Osteometer DTX-100). VDR and CTR alleles were determined by BsmI and AluI endonuclease restriction fragment analyses. Analysis of covariance was used as a statistical model. RESULTS: No significant differences in the forearm aBMD, BMC or in area values were observed between the VDR and CTR genotypes. Findings did not change after adjusting for demographic characteristics. CONCLUSIONS: The BsmI and AluI polymorphisms are not related to the forearm bone values either reflecting mass or geometrical variables in this male population.

Effect of digoxin on global respiratory muscle strength after cholecystectomy: a double blind study.

BACKGROUND: Upper abdominal surgery has been shown to impair the function of the respiratory muscles. In addition, controversial results have been reported concerning the effect of digoxin on the diaphragm. The aim of this study was to investigate further the mechanism(s) of respiratory muscle dysfunction after cholecystectomy and the effect of digoxin on the impaired respiratory muscle function. METHODS: Twenty three patients (four men) were studied before and 48 hours after surgery. Eleven received digoxin and 12 placebo. Respiratory muscle strength was assessed 48 hours after surgery by measuring mouth pressure during maximum static inspiratory (PImax) and expiratory (PEmax) efforts before and after 90 minutes of intravenous administration of 0.25 mg digoxin in a double blind, placebo controlled fashion. In addition, spirometric and pain measurements were performed. RESULTS: Postoperatively (+48 h) PImax and PEmax decreased significantly (p<0.01) from their preoperative values in both groups by a similar degree. After administration of digoxin or placebo only the digoxin group showed a significant increase in both PImax (p<0.02) and PEmax (p<0.05) with a mean increase of 15% for PImax and 12.3% for PEmax. The mean difference in PImax (DeltaPImax) and PEmax (DeltaPEmax) between the digoxin and placebo groups was 1.01 (95% CI 0.28 to 2.2) and 1.05 (95% CI 0.04 to 2.4), respectively. Estimates of postoperative pain did not differ between the two groups. Spirometric indices showed a similar restrictive defect postoperatively in both groups but did not change after digoxin or placebo. CONCLUSION: Digoxin improves the impaired global strength of the inspiratory and expiratory muscles after cholecystectomy and this may be clinically relevant. Muscle contractility could play a part in this impairment.

Effect of aminophylline on respiratory muscle strength after upper abdominal surgery: a double blind study.

BACKGROUND: The effect of aminophylline on maximum respiratory muscle strength in patients undergoing upper abdominal surgery was investigated. METHODS: An open pilot study was performed in which aminophylline was administered continuously for 48 hours after surgery (protocol I). In a second group of subjects aminophylline was given for 24 hours after cholecystectomy in a double blind placebo controlled trial (protocol II). Twelve patients participated in the pilot study (group A) and 25 in protocol II of which 14 received aminophylline (group B) and 11 placebo (control, group C). Respiratory muscle strength was assessed by measuring mouth pressures during maximum static inspiratory and expiratory efforts. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), vital capacity (VC), inspiratory maximum pressures (PImax), expiratory maximum pressures (PEmax) were measured 24 hours preoperatively, PImax and serum theophylline 24 hours postoperatively, and FEV1, FVC, VC, PImax, PEmax, and serum theophylline 48 hours after surgery. RESULTS: FEV1, FVC, and VC decreased in all groups of patients at +48 hours. PImax fell at +24 hours and +48 hours but this decrease was significantly smaller in the two groups who received aminophylline than in the control group. PEmax showed a decrease at +48 hours but this reduction was similar in all three groups studied, independent of the treatment given. These data suggest that either aminophylline had a protective effect only on the inspiratory muscles or, most probably, that the effect of aminophylline was central, reducing the phrenic nerve inhibition induced by cholecystectomy and thus improving diaphragmatic function. CONCLUSIONS: Upper abdominal surgery decreases inspiratory and expiratory muscle strength and aminophylline has a protective effect only on inspiratory muscle function. This may have important clinical applications in minimising pulmonary complications after cholecystectomy.

Orbital cellulitis due to mucormycosis. A case report.

A case of orbital cellulitis caused by mucormycosis developed in a patient subsequent to cataract extraction and during systemic steroid treatment for postoperative complications. Fatal mucormycosis is a rare disease usually beginning with a subcutaneous inflammatory lesion. As the subsequent development of orbital cellulitis is very rare, little has been published on this subject. In cases of subcutaneous mucormycosis, the diagnosis can easily be made by means of histologic examination of the lesion. However, early diagnosis is difficult in cases with orbital involvement, because the most common cause of orbital cellulitis is bacterial. Thus, orbital cellulitis caused by mucormycosis is often wrongly treated with antibacterial agents only, as histologic examination is neither easy nor part of any routine investigation. Therefore, a combined treatment using antibiotics and antifungal agents in immunusuppressed patients with this disease is advocated.