Stability, antioxidant activity, in vivo safety and efficacy of creams with standardized wild apple fruit extract: a comparison of conventional and biodegradable emulsifiers.

OBJECTIVE: The aim of the study was in vitro and in vivo characterization of cosmetic cream with 6% of standardized wild apple fruit extract, stabilized by conventional non-ionic emulsifier-CEW, in order to determine the influence of emulsifiers (conventional vs. biodegradable) on the characteristics of creams and their effects on the skin. METHODS: Organoleptic and physico-chemical (pH values and electrical conductivity) analysis was performed, determination of fruit acids-FAs content (using HPLC analysis) and estimation of its antioxidant activity-AA (using DPPH test) during 180 days. In vivo study included following examinations: screening of safety profile (after creams application under occlusion during 24 h at human skin); skin moisturizing potential, transepidermal water loss-TEWL, skin pH after 28 days of cream application and hypopigmentation efficacy 7 days of cream application at artificially induced skin hyperpigmentation. RESULTS: Investigated cosmetic cream-CEW showed satisfactory organoleptic, physico-chemical characteristics, stability, FAs content (0.13%) and AA (19.25 ± 0.67 %RSC) after preparation, which remained unchanged over the study period. In vivo investigation revealed absence of skin irritation after CEW's application under occlusion. An increase of skin moisturization (after 14 days ΔEC was 18.52 ± 11.51 and after 28 days of applications 16.52 ± 9.36) during 28 day-study, with unchanged TEWL and skin pH values was shown. Decrease of melanin index was revealed, too (after 7 days ΔMI was -31.40 ± 16.50). CONCLUSION: Cosmetic cream stabilized by conventional emulsifier showed better antioxidant potential and weaker moisturizing and hypopigmentation effects related to the cream with same composition but stabilized by biodegradable emulsifiers. Based on all mentioned above, investigated cosmetic cream might be considered for potential use as modern, stable, safe and efficient cosmetic product in the prevention and/or treatment of oxidative stress-related skin changes and/or damages, for moisturization of dry, even irritated skin as well as for lightening of hyperpigmented skin. RÉSUMÉ: OBJECTIF Le but de l'étude était la caractérisation in vitro et in vivo d'une crème cosmétique contenant 6 % d'extrait normalisé de pomme sauvage, stabilisée par un émulsifiant non ionique conventionnel-CEW, afin de déterminer l'influence des émulsifiants (conventionnels vs biodégradables) sur les caractéristiques des crèmes et les effets sur la peau. MÉTHODES: Des analyses organoleptiques et physico-chimiques (pH et conductivité électrique) ont été effectuées, la détermination de la teneur en acides de fruits et en acides gras polyinsaturés (par CLHP), et l'estimation de sa teneur en activité antioxydante (AA) (à l'aide du test DPPH) pendant 180 jours. L'étude in vivo comprenait les examens suivants : dépistage du profil d'innocuité (après application de crèmes sous occlusion pendant 24 h sur la peau humaine); potentiel d'hydratation de la peau, perte d'eau transépidermique (PETE), pH de la peau après 28 jours d'application de la crème et efficacité de l'hypopigmentation après 7 jours d'application de la crème sur une hyperpigmentation de la peau induite artificiellement. RÉSULTATS: La crème cosmétique-CEW étudiée a montré des caractéristiques organoleptiques, physico-chimiques, une stabilité, une teneur en AG (0,13 %) et en AA (19,25 ± 0,67 % RSC) satisfaisantes après préparation, qui sont demeurées inchangées au cours de la période de l'étude. L'étude in vivo a révélé l'absence d'irritation cutanée après l'application de CEW sous occlusion. Une augmentation de l'hydratation de la peau (après 14 jours de DEC était de 18,52 ± 11,51 et après 28 jours d'applications de 16,52 ± 9,36) pendant l'étude de 28 jours, avec une PETE et des valeurs de pH cutané inchangées, a été démontrée. Une diminution de l'indice de mélanine a été mise en évidence également (après 7 jours, ΔMI était de 31,40 ± 16,50). CONCLUSION: La crème cosmétique stabilisée par un émulsifiant conventionnel a montré un meilleur potentiel antioxydant et des effets d'hydratation et d'hypopigmentation plus faibles par rapport à la crème de même composition mais stabilisée par des émulsifiants biodégradables. D'après les données précédentes, la crème cosmétique étudiée pourrait être considérée comme un produit cosmétique moderne, stable, sûr et efficace dans la prévention et/ou le traitement des changements et/ou dommages cutanés liés au stress oxydatif, pour l'hydratation de la peau sèche, voire irritée, ainsi que pour éclaircir la peau hyperpigmentée.

Umbilical endometriosis associated with large umbilical hernia. Case report.

Umbilical endometriosis is a rare condition, usually following laparoscopic and surgical procedures involving the umbilicus.Spontaneous umbilical endometriosis occurring without any previous abdominal or uterine surgery is extremely rare. The maximal depth of penetration of the umbilical endometriosis described is up to fascial level. There have been only two cases of endometriosis reported arising within umbilical hernia. The authors report a case of a patient with spontaneous umbilical endometriosis associated with a large umbilical hernia, treated by surgical excision and mesh repair of the abdominal wall. To the best of our knowledge, this is the first described case of the association of umbilical endometriosis with a large umbilical hernia that requires prosthetic mesh repair of the abdominal wall defect.

Correlation of nuclear morphometry of primary melanoma of the skin with clinicopathological parameters and expression of tumor suppressor proteins (p53 and p16(INK4a)) and bcl-2 oncoprotein.

PURPOSE: To determine the correlation of nuclear morphometry of primary cutaneous malignant melanoma (CMM) with clinicopathological parameters and the expression of p53, p16INK4a, and bcl-2. METHODS: Image analysis and computerized nuclear morphometry were used in a series of 53 primary CMM (nodular melanoma/NM, N=33, and superficially spreading melanoma/SSM, N=20). The clinicopathological parameters determined for each tumor were histological type, maximal tumor diameter, Breslow thickness, Clark level, ulceration, mitotic index (MI) and pathological disease stage. Measured nuclear features included size, shape and optical density (OD). The results were correlated with the expression of p53, p16INK4a and bcl-2. RESULTS: Significant differences between NM and SSM were found for the nuclear area, OD, and perimeter (p<0.05). MI showed significant correlations with nuclear area, perimeter and Feret diameter (p<0.05). In relation to the Clark level, significant differences were found for OD (p<0.01) and circularity of nuclei (p<0.05) between levels II and IV, while the Breslow thickness was not significantly correlated with nuclear morphometric variables. Significantly negative correlations were observed between OD and the expression of p53 and bcl-2, while significant positive correlation was found between the nuclear circularity and p53 immunoreaction intensity. There was no significant correlation between the expression of p16INK4a protein and karyometric variables. CONCLUSION: OD and circularity are significantly correlated with p53 and bcl-2, and nuclear area with MI. These karyometric variables may determine a more aggressive phenotype of melanoma cells.

Lactobionic acid as antioxidant and moisturizing active in alkyl polyglucoside-based topical emulsions: the colloidal structure, stability and efficacy evaluation.

Cosmeceutical antioxidants may protect the skin against oxidative injury, involved in the pathogenesis of many skin disorders. However, an unsuitable topical delivery system with compromising safety profile can affect the efficacy of an antioxidant active. This study investigated the antioxidant potential of lactobionic acid (LA), a newer cosmeceutical active, per se (in solution) and incorporated into natural alkyl polyglucoside (APG) emulsifier-based system using 1,1-diphenyl-2-picrylhydrazyl free radical scavenging and lipid peroxidation inhibition assays. The α-tocopherol was used as a reference compound. The physical stability (using rheology, polarization microscopy, pH and conductivity measurements) of an Alkyl glucoside-based emulsion was evaluated with and without the active (LA); colloidal structure was assessed using polarization and transmission electron microscopy, rheology, thermal and texture analysis. Additionally, the safety profile and moisturizing potential were investigated using the methods of skin bioengineering. Good physical stability and applicative characteristics were obtained although LA strongly influenced the colloidal structure of the vehicle. LA per se and in APG-based emulsion showed satisfying antioxidant activity that promotes it as mild multifunctional cosmeceutical efficient in the treatment and prevention of the photoaged skin. Employed assays were shown as suitable for the antioxidant activity evaluation of LA in APG-based emulsions, but not for α-tocopherol in the same vehicle.

Does lactobionic acid affect the colloidal structure and skin moisturizing potential of the alkyl polyglucoside-based emulsion systems?

Moisturizing creams are the most prescribed products in dermatology, essential in maintaining healthy skin as well as in the topical treatment of some diseases. The irritation potential of commonly used emulsifiers and moisturizing ingredients, but also their mutual interactions, could affect the functionality and safety of those dermopharmaceutics. The aim of this study was to promote moisturizing alkyl polyglucoside (APG)-based emulsion as vehicle for lactobionic acid (LA), advantageous representative of the alphahydroxyacids (AHAs)-multifunctional moisturizers, assessing the safety for use (in vitro acute skin irritation test using cytotoxicity assay compared with in vivo data obtained using skin bioengineering methods) and in vivo moisturizing capacity (bioengineering of the skin). In order to investigate possible interactions between APG mild natural emulsifier-based emulsion and LA, a deeper insight into the colloidal structure of the placebo and the emulsion with LA was given using polarization and transmission electron microscopy, rheology, thermal and texture analysis. This study showed that APG-based emulsions could be promoted as safe cosmetic/dermopharmaceutical vehicles and carriers for extremely acidic and hygroscopic AHA class of actives (specifically LA); prospective safety for human use of both APG and LA with the correlation between in vivo and in vitro findings was shown. However, it was revealed that LA strongly influenced the colloidal structure of the emulsion based on APGs and promoted the formation of lamellar structures which reflects onto the mode of water distribution within the cream. The advantageous skin hydrating potential of LA-containing emulsion vs. placebo was unlikely to be achieved, pointing that emulsions stabilized by lamellar liquid crystalline structures probably are not satisfying carriers for highly hygroscopic actives in order to reach the full moisturizing potential. Safe and effective use on dry skin is presumed.

Dissociation of water on defective carbon substrates.

Using calculations from first principles, we found that water can dissociate over defective sites in graphene or nanotubes following many possible reaction pathways, some of which have activation barriers lower than half the value for the dissociation of bulk water. This reduction is caused by spin selection rules that allow the system to remain on the same spin surface throughout the reaction.

Influence of carbon curvature on molecular adsorptions in carbon-based materials: a force field approach.

A general force field methodology is developed for description of molecular interactions in carbon-based materials. The method makes use of existing parameters of potential functions developed for sp(2) and sp(3) carbons and allows accurate representation of molecular forces in curved carbon environment. The potential parameters are explicitly curvature and site dependent. The proposed force field approach was used in molecular dynamics (MD) simulations for hydrogen adsorption in single-walled carbon nanotubes (SWNTs). The results reveal significant nanotube deformations and the calculated energies of adsorption are comparable to the reported experimental heat of adsorption for H2 in SWNTs.

[Experimental and clinical possibilities of transplantation of the injured and totally devascularized spleen]. / Eksperimentalne i klinicke mogucnosti transplantacije konkvasirane ili totalno devaskularizovane slezine.

The most severe spleen lesions with conquasation and devascularisation of entire organ, when it is practically impossible to do any preservating surgical procedure, are the true indications for the transplantation of this extremely important immunological organ. We have performed the evaluation of the surgical procedure of heterotopic auto transplantation in the 30 dogs with severe spleen lesions. Simulation of totally devascularized spleen with the lesions of V degree was performed by disrupting all segmental blood vessels with deep and long longitudinal transhilar incision. During the 3 months follow-up period, animals were subjected to numerous explorations in order to macroscopically and histologically valuate the implant. In most cases (80-85%) implants had complete vitality with the preservation of normal tissue architecture, while 15-20% of implants had partial or total fibrosis. There were no mortality and no complications after this preservation procedure. The presence of fibrosis in some implants suggests that the implant preparation should be better performed and that transplantation of larger tissue volume is needed. Enriched with this experimental experience we have performed heterotopic auto transplantation in 2 patients with spleen lesion of V degree (car accident and injury at work) with very satisfactory results.

[Use of fibrin glue in the prevention of leakage in pancreatico-jejunal anastomoses]. / Primena fibrinskog lepka u prevenciji popustanja pankreasno-jejunalne anastomoze.

The aim of this study was to test the protective effects of fibrin sealing on the pancreatico-jejunostomy (PJA), the high-risk anastomosis following pancreas head resection. Experimental study was performed on the mongrel dogs, divided in two groups (20 animals each): Experimental group-with end to end "dunking" PJA, protected by temporary occlusion of the pancreatic duct with fibrin sealant/Tissucol/Immuno Ag/, while control group was without any protective procedure. The animals were followed 5 months in order to study: protective effects of such procedure on the PJA quantified with the percent of anastomotic leakage, effects of the exocrine secretion and effects the endocrine function Results: PJA leakage occurred in 13.33% in control group. No leakage was registered in experimental group. Biochemical, histological and electron microscopic study showed slight transitory elevation of amylase levels. Fibrin glue plug was dissolved and pancreatic juice output was reestablished 12th days postoperatively. Long term follow-up showed no damages of the endocrine and exocrine pancreas. Pancreatic duct occlusion with fibrin glue appeared to be an useful method in the prevention of pancreatico-jejunostomy leakage, without negative effects on the exocrine and endocrine pancreas.

[Ochronosis--an autopsy case report]. / Ohronoza--autopsijski prikaz slucaja.

The authors have presented a case of ochronosis, as the incidental finding during the autopsy of a female patient, aged 59 years. It was the case of suicidal drug poisoning. Ochronosis is a rare disease, with chronic benign course, but frequently followed by complications. Histopathological criteria for the diagnosis of this disease are described in detail.

[Treatment of diabetics with metformin]. / Lechenie na diabetno bolni s metformin.

After a brief survey of the mechanism of biquanides treatment and their indications and contraindications with the peroral treatment of diabetes mellitus, the adverse effects of that treatment are stressed upon, manifested mainly in lactacidosis. The latter is indicated to be most frequently found during the treatment with tenformin, rarely -- with buformin and most rarely and in a lighter form -- with metformin. That uneven effect of biquanide preparations is associated with a certain difference in their pharmacodynamics and pharmacokinetics. On the other hand -- those adverse effects result most frequently from unproper treatment carried outnot observing the indications and particularly the contraindications and surpassing the therapeutic doses. Very good results are reported, that were obtained by the authors, in the treatment with metform of 70 diabetic patients with insulin-independent type of diabetes and body overweight, that failed to respond to the treatment with a reducing diet or a diet and sulfurea preparations and resistant to insulin. Indications for that treatment are presented as well as the necessity of strict observation of the contraindications for its administration.