Effect of novel carboxymethyl cellulose-based dressings on acute wound healing dynamics.

The clinical implications and efficacy of newly developed modified cellulose materials were evaluated in an acute wound animal model. In the current study, sixty male rats were divided into four groups. A full-thickness circular excision wound was created in the suprascapular area. Newly developed matrices (acidic partially carboxymethylated cellulose; acidic partially carboxymethylated cellulose impregnated with a povidone-iodine solution) were applied in two test groups, while fifteen animals were used as a control group without any primary dressing. Aquacel Ag, a clinically used dressing, was selected as the reference material. To compare the efficacy in vivo, the wound size and production of selected cytokines and growth factors (TNF-α, TGF-ß1, and VEGF), which play a key role in the healing process, were measured at two, seven, and fourteen days after surgery. The activity of matrix metalloproteinases 2 and 9, which actively participate in cell signalling and are essential for tissue remodelling, was determined in wound tissue by gelatin zymography. A positive effect of the newly developed dressing materials on the healing process, tissue granulation, and wound re-epithelialisation was demonstrated.

Composite Hemostatic Nonwoven Textiles Based on Hyaluronic Acid, Cellulose, and Etamsylate.

The achievement of rapid hemostasis represents a long-term trend in hemostatic research. Specifically, composite materials are now the focus of attention, based on the given issues and required properties. In urology, different materials are used to achieve fast and effective hemostasis. Additionally, it is desirable to exert a positive influence on local tissue reaction. In this study, three nonwoven textiles prepared by a wet spinning method and based on a combination of hyaluronic acid with either oxidized cellulose or carboxymethyl cellulose, along with the addition of etamsylate, were introduced and assessed in vivo using the rat partial nephrectomy model. A significantly shorter time to hemostasis in seconds (p < 0.05), was attributed to the effect of the carboxymethyl cellulose material. The addition of etamsylate did not noticeably contribute to further hemostasis, but its application strengthened the structure and therefore significantly improved the effect on local changes, while also facilitating any manipulation by the surgeons. Specifically, the hyaluronic acid supported the tissue healing and regeneration, and ensured the favorable results of the histological analysis. Moreover, the prepared textiles proved their bioresorbability after a three-day period. In brief, the fabrics yielded favorable hemostatic activity, bioresorbability, non-irritability, and had a beneficial effect on the tissue repair.

Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin.

This work presents a deeper pharmacological evaluation of two formerly prepared and characterized, and highly in vitro cytotoxic platinum(II) oxalato complexes [Pt(ox)(L1)2] (1) and [Pt(ox)(L2)2] (2), containing the derivatives of cyclin-dependent kinase inhibitor (CDKi) seliciclib ((R)-roscovitine, CYC202) coordinating as N-donor carrier ligands, i.e., 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (L1) and 2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine (L2). The positive results of in vitro cytotoxicity screening on human cancer cell lines (HeLa, HOS, A2780, A2780R, G361 and MCF7 with IC50 at low micromolar levels) published previously, motivated us to perform extended preclinical in vitro experiments to reveal the mechanisms associated with the induction of cancer cell death. In addition, the in vivo antitumor activity was evaluated using the mouse lymphocytic leukaemia L1210 model. The obtained results revealed that complex 1 exceeds the antitumor effect of cisplatin (as for the extension of life-span of mice) and shows far less adverse effects as compared to reference drug cisplatin. The in vitro and ex vivo studies of cellular effects and molecular mechanisms of cell death induction showed that the mechanism of action of complex 1 is essentially different from that of cisplatin. The obtained results showed a possible way how to obtain antitumor active platinum(II) oxalato complexes with better therapeutic profile than contemporary used platinum-based therapeutics.

Cytotoxic, anti-cancer, and anti-microbial effects of different extracts obtained from Artemisia rupestris.

Artemisia rupestris is a part of traditional Kazakh folk medicine. Extracts obtained from this plant are used to treat various diseases, including cancer. This study evaluates the anti-microbial, cytotoxic, and anti-cancer effects of different extracts of the plant. Different extraction techniques were used and the resultant activities were compared. Extracts of A. rupestris were prepared from the flowers plus the leaves and from the stems. The antimicrobial activity against Candida albicans and Staphylococcus aureus was quantified. Cell lines L1210 and THP-1 were used to evaluate the cytotoxic potential of these extracts in vitro. The anti-cancer effect was tested using L1210-induced tumorgenesis in mouse model. The aqueous extract of stems was the most active against C. albicans, whereas the methanolic extract of flowers plus leaves especially inhibited the growth of S. aureus. The aqueous extracts were found to be non-cytotoxic for both cell lines, whereas the lipophilic extracts showed cytotoxic effects. The extract obtained from flowers plus leaves was more cytotoxic than that from stems. The tested extracts showed no anti-cancer potential. The results obtained testify to the relatively safe consumption of aqueous extracts of A. rupestris, but lipophilic extracts showed toxic effects and their consumption should be considered more carefully.Key words: L1210 cell line THP-1 cell line microwave-assisted extraction ultrasonic-assisted extraction Candida albicans Staphylococcus aureus.

Molecular, cellular and pharmacological effects of platinum(II) diiodido complexes containing 9-deazahypoxanthine derivatives: A group of broad-spectrum anticancer active agents.

The platinum(II) iodido complexes 1-5 of the general formula cis-[PtI2(Ln)2], where Ln stands for O-substituted 9-deazahypoxanthine derivatives, were prepared and thoroughly characterized by various techniques, including multinuclear 1D and 2D NMR spectroscopy. The complexes were screened for their anticancer potential in vitro on ten human cancer cell lines, concretely breast adenocarcinoma (MCF7), osteosarcoma (HOS), lung carcinoma (A549), cervix epithelioid carcinoma (HeLa), malignant melanoma (G-361), prostate carcinoma (22Rv1, PC-3), hepatocellular carcinoma (HepG2), ovarian carcinoma (A2780) and cisplatin-resistant ovarian carcinoma (A2780R). The complexes exhibited significant wide-spectrum anticancer activity in vitro against all the employed cell lines, with IC50≈0.5-24.0µM. Very good correlation between the lipophilicity parameter log P and IC50 values of anticancer activity in vitro were obtained by simple QSAR analysis. The most lipophilic complexes 2, 4 and 5 showed the best results, as they reached the sub-micromolar IC50 values against the A2780 and A2780R sub-lines, with the best result equal 0.5±0.1µM on A2780 for complex 5. The in vivo testing of the representative complexes 1, 4 and 5 (applied at the same dose of Pt as 2mg/kg dose of cisplatin) on a L1210 leukaemia model revealed their positive effect on the prolongation of the mean survival time, even if it was lower than that of cisplatin. The 1H NMR interaction study revealed the ability of complexes to interact with glutathione (GSH) and 5'-guanosine monophosphate (GMP) and overall higher stability of the complexes 1-5 as compared to cisplatin. The electrospray-ionization mass spectrometry experiments with complex 1 identified the formation of a rich collection of hydrolytic species in water-containing media after 24h and the interaction intermediates with sulfur-containing biomolecule l-cysteine, but not with the reduced glutathione at physiologically relevant concentration levels.

Hepatoprotective and proapoptotic effect of Ecballium elaterium on CCl4-induced hepatotoxicity in rats.

OBJECTIVES: To investigate the effects of perorally administered juice on tetrachloromethane (CCl4)-induced hepatotoxicity model in rats. METHODS: Male Wistar rats were tube-administrated silymarin, Ecballium juice at 0.2 mL/kg and 0.7 mL/kg daily for 3 consequent days, i.e., 3.28 µg and 11.48 µg of cucurbitacin B per kg of body weight respectively. On the third day, liver damage was induced by intraperitoneal application of CCl4. On the fourth day, abdominal cavity was macroscopically examined and liver samples were taken for histopathological and immunochemical evaluation. HPLC was used to determine the content of the active substance cucurbitacin B. RESULTS: The experiment revealed that 0.7 ml/kg juice concentration expressed the highest pro-apoptotic activity, but with prevailing negative effects. Compared with the lower concentration, there was an observable vasodilatation with consequent interstitial hemorrhages and a larger scope of inflammatory damage, which suppressed the hepatoprotective effect. In the 0.2 mL/kg concentration, there was a smaller pro-apoptotic activity but other parameters had better results, and the liver parenchyma damage was reversible. CONCLUSIONS: No reactions confirming the potentially allergic effect on laboratory rats were observed; its hepatoprotective and anti-inflammatory effect was confirmed on a model of acute liver damage.

Local tissue reaction after the application of topical hemostatic agents in a rat partial nephrectomy model.

Various hemostatics are used for renal surgical procedures. We investigated the hemostatic efficacy of cellulose derivatives on the model of partial nephrectomy in rats focusing on the local reaction of renal parenchyma. A total of 50 Wistar rats were divided into five groups of 10 animals each. Partial nephrectomy of the caudal pole without hilar vascular control was performed. Oxidized cellulose (OC), sodium salt of oxycellulose (OCN), carboxymethyl cellulose (CMC), dialdehyde cellulose (DAC), and gelatin-based hemostatic (C) were applied to the bleeding wounds. The time to hemostasis was monitored. Half of the animals were euthanized after 3 days, the second half 30 days from the experiment start date. The left kidney was excised and subjected to histopathological examination. The biochemical data was subjected to statistical analysis. The time to hemostasis in all groups was significantly less than in the C group (in OC p = 0.0057, OCN p = 0.0039, CMC and DAC p = 0.0001). In the C group, massive hemorrhages and necrosis did occur. In the OC and OCN groups, there were regenerative changes, a receding inflammatory reaction and hemorrhage. DAC caused an immune reaction and massive interstitial hemorrhages with biochemical signs of liver damage. Parenchyma in CMC revealed a reduction of necrosis and interstitial hemorrhages with regenerative processes. The most effective hemostatics were CMC and OC, achieving the best results both in the time to hemostasis, and for histopathological evaluation.