Cu(II)–poly(L-arginine) complexes. Potentiometric and spectral characterization of amine and peptide nitrogen ligands

The study of Cu(II)–poly(L -arginine) complexes by potentiometric titration, as well as by optical, circular dichroism, and infrared spectra, provides information about the nature of ligands and the coordination sphere around the metal ion. Three different complexes have been identified. The first, which is formed below pH 8, contains two guanidinium nitrogens and two water molecules at the corners of the coordination square. The constant of the overall process as determined by the Gregor method equals 2.0 ± 0.1 × 10^?9. The two other complexes form between pH 8 and 10.5 and they contain two guanidinium and two peptide nitrogens as nearest ligands. One of them is a monomer and the other probably a dimer, which differ in the symmetry of the coordination sphere around the cupric ion. The optical spectra of the three complexes show an absorption band at 260 nm that we have assigned to a charge-transfer transition between a σ metal nitrogen (amine) molecular orbital and a d_x2_?y2 metal orbital. The spectra of the two complexes containing peptide nitrogens exhibit another absorption band at 320 nm, which we have assigned to a charge transfer from a π orbital of the amide group to the d_x2_?y2 metal orbital.     

Formation and structure of Cu (II) — poly (L-arginine) complexes in aqueous solution

Cu (II) — poly (L-arginine) (PLA) complexes have been studied using potentiometric titrations, optical absorption and circular dichroism spectra. Three different complexes have been observed. The first one (complex I) is formed up to pH 8 and results from the coordination of two guanidinium groups to the metal ion. The second and third complexes (complexes II_A and II_B) are formed between pH 8 and 11, in different proportions which are dependent on PLA: Cu molar ratio. In these two complexes two guanidinium groups and two peptide nitrogens participate as ligands around the copper ion.     

Physicochemical studies of the iron(III)-carminomycin complex and evidence of the lack of stimulated superoxide production by NADH deydrogenase

Fe(III) complex of an antitumoral antibiotic carminomycin has been studied. Using potentiometric and spectroscopic measurements we have shown that carminomycin forms with Fe(III) a well-defined species in which three molecures of drug are chelated to one Fe(III) ion. This occurs with the release of one proton per molecule of drug. Magnetic susceptibility measurements suggest that six oxygen atoms are bound to iron. The stability constant is 3·10³⁴. The in vitro inhibition of P 388 leukemia cell growth by this complex compares with that of the free drug. This complex, unlike the free drug, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase.     

Effects of fetal urinary corticosteroids, catecholamines and kallikrein on PGE2 synthesis in monolayer cultures of human amnion and chorion cells

We have studied the effects of several compounds isolated from fetal urine on the production of PGE2 by amnion and chorion cells which were maintained in primary monolayer culture. We conclude that desoxycorticosterone and vanillylmandelic acid stimulate PGE2 synthesis by amnion, but adrenaline and kallikrein increase the biosynthesis of PGE2 by chorion. These data suggest that human fetal urine could play a major role in events of parturition.     

Physical,Behavioral, and Body Image Characteristics in a Tri‐Racial Group of Adolescent Girls

Objectives: The purpose of this study was to evaluate physical characteristics, nutrient intake, physical activity level, and body image in white (CC), African‐American (AA), and Hispanic‐American (HA) female adolescents. Research Methods and Procedures: High school volunteers were solicited for this study. Self‐reported information was used to determine subject characteristics, family income, physical activity, body image, and nutrient intake. Physical evaluations were used to determine body mass index, percent body fat, fat distribution, resting heart rate, and blood pressure (BP). Results: Results showed that AA girls displayed significantly higher diastolic BP than HA girls (p = 0.029). CC adolescents showed greater physical activity (p = 0.010) and lower adiposity than HA adolescents (p = 0.048), as well as lower subscapular skinfold than AA adolescents (p = 0.018). AA adolescents selected a higher ideal body size than CC girls (p = 0.038). There was also a significant difference in percentage carbohydrates (p < 0.034) and cholesterol consumed (p < 0.016) among groups, with CC girls showing the highest values for carbohydrates and lowest values for cholesterol intake among groups. Discussion: Given our findings of higher adiposity and lower physical activity levels in HA adolescents and greater diastolic BP levels and subscapular skinfold in AA adolescents, more interventions should be targeted toward improving health‐related variables among minority populations.     

Resistance to Arsenic- and Antimony-Based Drugs

Organic arsenicals were the first antimicrobial agents specifically synthesized for the treatment of infectious diseases such as syphilis and sleeping sickness. For the treatment of diseases caused by trypanosomatid parasites, organic derivatives of arsenic and the related metalloid antimony are still the drugs of choice. Arsenic trioxide, As203, has been used for a long time in traditional Chinese medicines for treatment of various diseases, and it has recently been shown to be clinically active in acute promyelocytic leukemias. Resistance to metalloid salts is found in bacteria, fungi, parasites and animals. In some organisms, resistance involves overproduction of intracellular thiols. In many cases, resistance to arsenic salts is the result of removal of the metalloid from the cytosol usually by extrusion from the cell. In eukaryotes resistance to arsenic and antimony is conferred by membrane transport proteins of the MRP family. The human MRP1, a member of this family, is frequently amplified in cancer cells and it is well-documented that MRPl-overexpressing cells poorly accumulate arsenic and antimony because of enhanced cellular effiux which depends on the presence of GSH.     

The Relationship Between Fat Distribution and Coronary Risk Factors in Sedentary Postmenopausal Women On and Off Hormone Replacement Therapy

The purpose of this study was to examine the relationship between fat distribution and coronary risk factors (CRF) in sedentary overweight postmenopausal women both on and off hormone replacement therapy (HRT). Medical records and information were abstracted from nonsmoking women entering a weight loss program. A total of 33 women on HRT (mean age=50.12 ± 5.2) and 51 nonusers (mean age=52.52 ± 7.8) fulfilled subject eligibility requirements and were included in the data analysis. Results showed a significantly lower waist-to-hip ratio (WHR) (p=0.009) and waist (p=0.010) and greater levels of high-density lipoprotein cholesterol (HDL-C) (p=0.035) in HRT users than in nonusers. After converting correlations to standard Z-scores and performing z-tests, the correlation between total cholesterol (T-Chol) and WHR was significantly greater in nonusers than in HRT users (p=0.038). A multiple regression analysis showed differences between groups in the ability of age and anthropometric variables to predict CRF. Although T-Chol could be predicted in nonusers(r²=0.24; ^p=0.011), very low-density lipoprotein cholesterol (VLDL-C) and systolic blood pressure (SBP) could be significantly predicted in HRT users only (r²=0.28, P=0.055 and r²=0.40, p=0.005 for VLDL-C and SBP, respectively). These data suggest that there are differences between HRT users and nonusers in predictors of CRF, central adiposity, HDL-C, and the relationship between WHR and T-Chol. It is concluded that the significantly lower levels of central adiposity observed in HRT users may have clinical benefits with regard to CRF.     

Raman confocal microscopy and biophysics multiparametric characterization of the skin barrier evolution with age

Skin aging is a multifactorial phenomenon that involves alterations at the molecular, cellular and tissue levels. Our aim was to carry out a multiparametric biophysical and Raman characterization of skin barrier between individuals of different age groups (<24 and >70 years old). Our results showed a significant decrease of lipids to proteins ratio overall the thickness of the stratum corneum and higher lateral packing in the outer part of the SC for elderly. This can explain the decrease in trans epidermal water loss measured values rather than only SC thickening. Both age groups showed similar water content at SC surface while elderly presented higher water content in deep SC and viable epidermis. Mechanical measurements showed a decrease in the elasticity and an increase in the fatigability with age and were correlated with partially bound water. Highest correlation and anti-correlation values were observed for the deepest part of the SC and the viable epidermis.     

Effect of polyisobutylcyanoacrylate nanoparticles and Lipofectin® loaded with oligonucleotides on cell viability and PKCα neosynthesis in HepG2 cells

The aim of the present study was to evaluate the inhibitory effect on protein kinase Ca (PKCα) neosynthesis of antisense oligonucleotides delivered by two types of carriers. First, PKCα antisense oligonucleotides were associated with polyisobutylcyanoacrylate (PIBCA) nanoparticles pre-coated with cetyltrimethyl ammonium bromide (CTAB), a hydrophobic cation. Adsorption of oligonucleotides onto PIBCA nanoparticles was shown to be a saturating process. From these studies, it was possible to identify two types of particles: positively and negatively charged. Secondly, Lipofectin® was used as another carrier system. These systems were incubated with HepG2 cells. Toxicity was evaluated by the MTT assay, and PKCα neosynthesis was determined by Western blots in conditions where nanoparticles and Lipofectin® were not inducing cytotoxicity. It was observed that both mismatch and antisense oligonucleotides induced an inhibition of PKCa neosynthesis when loaded onto cationic or anionic nanoparticles as well as when complexed to cationic liposomes (Lipofectin®). This non-specific effect was only observed in the phase of PKCα neosynthesis when the cells were first depleted in PKCa by phorbol 12-myristate β-acetate (12-PMA) and in the absence of serum. These results strongly suggest that delivery systems, PIBCA nanoparticles or Lipofectin®, containing a positively charged component (CTAB or cationic lipids), are able to induce a perturbation in the intracellular metabolic activity. In conclusion, it was shown that the commonly used strategy of oligonucleotides targeting with cationic non-viral vectors may display non-specific effects which can lead to artifactual results.