Nano-Leish-IL: A novel iron oxide-based nanocomposite drug platform for effective treatment of cutaneous leishmaniasis.

Kinetoplastids are infamous parasites that include trypanosomes and Leishmania species. Here, we developed an anti-Leishmania nano-drug using ultra-small functional maghemite (γ-Fe2O3) nanoparticles (NPs) that were surface-doped by [CeLn]3/4+ to enable effective binding of the polycationic polyethylenebyimine (PEI) polymer by coordinative chemistry. This resulting nano-drug is cytolytic in-vitro to both Trypanosoma brucei parasites, the causative agent of sleeping sickness, as well as to three Leishmania species. The nano-drug induces the rupture of the single lysosome present in these parasites attributed to the PEI, leading to cytolysis. To evaluate the efficacy of a "cream-based" version of the nano-drug, which was termed "Nano-Leish-IL" for topical treatment of cutaneous leishmaniasis (CL), we developed a rapid screening method utilizing T. brucei parasites involved in social motility and demonstrated that functional NPs arrested the migration of the parasites. This assay presents a surrogate system to rapidly examine the efficacy of "cream-based" drugs in topical preparations against leishmaniasis, and possibly other dermal infectious diseases. The resulting Nano-Leish-IL topical preparation eliminated L. major infection in mice. Thus, this study presents a novel efficient nano-drug targeting the single lysosome of kinetoplastid parasites.

Moistened hands do not necessarily allude to high quality fingerprints: the relationship between palmar moisture and fingerprint donorship.

We explored the quality distribution of ninhydrin-developed prints on A4 bond paper in two groups of individuals, in Israel and in India. While the quality distributions of the developed marks in both countries had some dissimilarities, both groups showed the expected bell-shape distribution, with the majority of the donors belonging to the central zone, defined as "average" or "good." Attempt was made to correlate between a physiological feature, palmar moisture, and the fingerprint donorship. As a rule, high fingermark quality could be associated with sweating hands, but there were individuals with moist palms whose fingermarks had a low score and vice versa. This finding supports the logical but hitherto unproven assumption that besides the amount of palmar sweat, the other physiological factor governing the prints' quality is the total amount of substrate, amino acids in this case, in the latent deposits, which depends on the substrate concentration in the sweat.

Identification of firearms handling by the [Fe(PDT)(3)](2+) complex: Chemical and time-dependent factors.

Handling of a gun results in the formation of invisible impressions, caused by transfer of iron traces to the skin surface. Visualization of these impressions is possible by spraying the palms with a solution of 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine (PDT), which forms a magenta complex with iron(II) residues. Hence, mark intensity is directly related to the amounts of iron transferred to the palm. Palmar sweat plays a major role in iron transfer from the firearm to the hand. More factors, however, are involved in this process. Three time-dependent factors have been studied with relation to their effect on the developed mark: the gripping duration of the weapon; the time elapsed from the contact; and the rate of iron dissolution in aqueous solutions containing sweat components in physiological concentrations. We found that the amounts of iron transferred to the palm depend on both, the gripping period and the levels of palmar moisture. Thus, only a few seconds of gripping were required for developing good marks (corresponding to 80ngcm(-2) of iron) on highly-moistured hands, much longer gripping periods were necessary for developing marks of similar intensity on relatively dry hands. Experiments that aimed at studying the effect of sweat components on metallic iron dissolution were carried out in aqueous solutions. It was found that chloride ions in physiological concentrations remarkably enhanced the dissolution, while l-serine, the major amino acid in palmar sweat, had a detrimental effect on this process. Urea, another sweat component, had only a minor effect on the dissolution rate.

Identification of firearms holders by the [Fe(PDT)3](+2) complex. Quantitative determination of iron transfer to the hand and its dependence on palmar moisture levels.

Quantitative data are reported for the first time on the amounts of iron, which are transferred to the hand upon holding a firearm. Iron levels between 21-315 ng/cm2 were found on volunteers' palms after a single holding of a handgun. Determination of the iron traces was accomplished spectrophotometrically using 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine (PDT) as a complexing agent. The transfer of iron from firearms to the palm was found to be, by and large a chemical (dissolution) rather than mechanical dislodgement. The prime factor that determines the amount of iron transferred from the firearm to the hand is the moisture level on the palm. These findings are likely to be of importance in courts of law, as well as in the war against terrorism and serious crime.

The connection between in vitro water uptake and in vivo skin moisturization.

BACKGROUND/PURPOSE: Humectancy or hygroscopy is the water absorption tendency of a substance from the surroundings. Our interest, from the clinical point of view, consists of correlating this tendency in vitro and its effect in vivo for the development of drugs and formulations for the treatment of dry skin syndrome or diseases accompanied by dry skin. METHOD: In vitro, water absorption was measured using the comparative isopiestic method. This method is based on bringing the vapor of the water to isothermal equilibrium between a reference system and the material to be studied. The in vivo model on guinea-pigs for the dry skin syndrome tested the therapeutic ability of mono-, di- and tri-glycerols to provide moisture to dry skin leading to healing. The moisture content in the stratum corneum was measured with a Corneometer CM 825 PC that measures merely the presence of high dielectric material (humectant or water), whereas the Mexameter MX 16 measures a pathological parameter - the erythema. RESULTS: Adding hydroxyl groups to a consecutive set of polyhydroxyalkanes increases the humectancy of the polyols in vitro. This elevation was found to be linear at low relative humidities (Relative humidity=31.9% and 37 degrees C). In vivo, moisture was returned to normal within a week in all three groups. However, only glycerol managed to abolish the erythema within 7 days. CONCLUSION: A rise in water absorption ability in vitro, at a rate of about 0.25 mol water per hydroxyl group was revealed in a consecutive set of glycerols (mono-, di- and tri-glycerols). One would expect that the better humectant is a material, i.e. in which the higher its physical ability to hold water in vitro the more effective it will be in recovering skin dryness. We have found, however, that glycerol, which has the lowest humectant activity in vitro, from the set of glycerols, di- and tri-glycerol, has been proven to be the best for eliminating the signs of skin dryness. Accordingly, we propose to distinguish between the in vitro humectancy (i.e. the water uptake of a material), and its in vivo moisturizing effect, i.e. its ability to cure skin dryness and erythema. This finding supports our conclusion that the connection between in vitro humectancy and in vivo moisturization is not a simple correlation.