Anti-proliferative and anti-angiogenic effects of CB2R agonist (JWH-133) in non-small lung cancer cells (A549) and human umbilical vein endothelial cells: an in vitro investigation.

Non-small cell lung cancer has one of the highest mortality rates among cancer-suffering patients. It is well known that the unwanted psychotropic effects of cannabinoids (CBs) are mediated via the CB(1) receptor (R), and selective targeting of the CB(2)R would thus avoid side effects in cancer treatment. Therefore, the aim of our study was to evaluate the effect of selective CB(2)R agonist, JWH-133, on A549 cells (non-small lung cancer) and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assay and DNA fragmentation assay were employed to evaluate the influence of JWH-133 (3-(1,1-dimethylbutyl)- 1-deoxy-Δ8-tetrahydrocannabinol) on investigated cancer cells. In addition, migration assay and gelatinase zymography were performed in HUVECs to asses JWH-133 anti-angiogenic activity. Our study showed that JWH-133 exerted cytotoxic effect only at the highest concentration used (10(-4) mol/l), while inhibition of colony formation was also detected at the non-toxic concentrations (10(-5)-10(-8) mol/l). JWH-133 was also found to be able to induce weak DNA fragmentation in A549 cells. Furthermore, JWH-133 at non-toxic concentrations inhibited some steps in the process of angiogenesis. It significantly inhibited endothelial cell migration after 17 h of incubation at concentrations of 10(-4)-10(-6) mol/l. In addition, JWH-133 inhibited MMP-2 secretion as assessed by gelatinase zymography. The present study demonstrates the in vitro anti-proliferative and anti-angiogenic potential of CB(2)R agonist, JWH-133, in nonsmall lung cancer cells and HUVECs. Our results generate a rationale for further in vivo efficacy studies with this compound in preclinical cancer models.

Simple interrupted percutaneous suture versus intradermal running suture for wound tensile strength measurement in rats: a technical note.

BACKGROUND: In this experimental study, simplicity of measurement and wound tensile strength of wounds fixed by simple interrupted percutaneous suture (SIPS) and intradermal running suture (IRS) were compared. METHODS: Twenty-eight male Sprague-Dawley rats were used for the experiment and separated into two groups: SIPS group and IRS group. Under general anesthesia, two parallel full-thickness (4-cm) skin incisions were made on the back of each rat. Wounds in the SIPS group were closed using 4 interrupted percutaneous sutures, whereas wounds in the IRS group were closed by intradermal running suture. Seven animals from each group were sacrificed at 2 and at 5 days after surgery for tensile strength testing. RESULTS: The wound tensile strength of IRS wounds was significantly higher than that of SIPS wounds at 2 days (SIPS = 2.9 +/- 0.8 vs. IRS = 3.7 +/- 0.9 g/mm(2), p < 0.05) and at 5 days (SIPS = 5.6 +/- 1.3 vs. IRS = 7.1 +/- 1.2 g/mm(2), p < 0.01). In addition, the measurement of IRS wounds was easier and faster due to removal of only one suture. CONCLUSIONS: These findings highlight the advantages of expanding the use of IRS suturing in experimental studies conducted on rats.

[The influence of laser irradiation with different power densities on incisional wound healing in healthy and diabetic rats]. / Vplyv laserového ziarenia rôznych intenzít na hojenie incíznych rán u zdravých a diabetických potkanov.

INTRODUCTION: The optimal parameters of low level laser therapy (LLLT) are still under debate. It has been documented that a dose or 5 J/cm2 would be capable to accelerate the wound healing process in patients. However, the optimal delivering form, i.e. power intensity, is unknown. Therefore, the aim of our study was to compare different power densities of LLLT. MATERIALS AND METHODS: Sixteen male Sprague-Dawley rats were included in this experiment and randomized into two groups, normal healthy group and streptozotocine induced diabetic group. In general anesthesia four full thickness skin incisions were performed under standard aseptic conditions on the back of each rat and immediately closed using intradermal running suture. Three wounds were stimulated with diode laser (wavelength: 635 nm; daily dose 5 J/cm2; power densities: 1 mW/cm2, 5 mW/cm2 and 15 mW/cm2) each with different power density while the fourth wound served as control. Six days after surgery animals were sacrificed and samples removed for histological evaluation. RESULTS: Our study demonstrated that LLLT positively influences wound healing. The most significant changes were observed in wounds stimulated at the highest power density 15 mW/cm2. Since using the highest power density the shortest time is needed to achieve the optimal daily dose of 5 J/cm2, it can be suggested that 15 mW/cm2 might be optimal parameter for such a therapy in patients.

Early changes in the tensile strength and morphology of primary sutured skin wounds in rats.

The specific aim of this study was to measure the TS of rat skin wounds during the first week following surgical injury. Biomechanical and histological data were collected daily (days 1 to 7 following surgery) from separate groups of Sprague-Dawley rats (N = 12) each with two 3 cm long parallel skin incisions on the back. The wounds were immediately closed by four simple sutures. A control group (N = 15) was used to obtain TS measurements of unwounded skin. TS was measured by applying a ramp load until wound separation and estimated by dividing the yield strength by the wound area. The time course of biomechanical recovery followed a step-plateau pattern with the largest increase in TS observed one day after surgery (0 - 1.60 g/cm(2)). The plateau stage extended from day 1 to 5 (1.60 - 3.88 g/cm(2)). The final step (day 5-7) indicated a period of rapid rise in wound TS (3.88 - 11.57 g/cm(2)). Since even on day 7 the mean TS was only 4% of unwounded skin, the wound had to be protected from tensile loads. Histological analysis confirmed that the early changes in TS (day 1) correlated with the fibrin accumulation of the wound edges followed by a plateau stage caused by the tissue proliferation. The rapid increase in wound TS was characterized by cross-linking the incisions with collagen fibres with escalating organization. We conclude that from a biomechanical perspective, sutures can be removed during the "plateau phase", but the wound must be protected from tensile loads.

[Different views on the association between cannabinoids and cancer]. / Rôzne pohl'ady na vzt'ah kanabinoidov a rakoviny.

Cannabinoids are the major active components of the most widely used illegal drug - marihuana. They have a long history of the medicinal use. However, they are still a controversial topic in oncological praxis. Cannabinoids play a role in different organs of human body and they are an integral part of the newly described endocannabinoid system, which regulates several body functions. The important function of endocannabinoids which is related to cancer, is the regulation of cell cycle and cell survival pathways. Presented review gives three different views on the association between cannabinoids and cancer. First, the treatment of adverse symptoms of oncological therapy - nausea and vomiting inhibition, appetite stimulation, pain relieving, mood modulation and muscle stiffness relieving. Second, in the late 1990s, three possible mechanisms of antitumour action were identified - apoptosis induction, direct cell cycle arrest and angiogenesis and metastasis inhibition. The phase I/II of clinical trials are carrying out in Spain. They study effects of local administration of tetrahydrokanabinol on the growth of glioblastoma multiforme. Third, the results of the newest study focused on the association between cannabinoids use and cancer risk showed no significant association between increased cancer incidence and cannabinoids use and it does not depend on the amount of used cannabis. It is important to establish the association between marihuana use and cancer risk regarding the consideration of advantages and risks of medicinal cannabinoids use and the impact on public health.

[Effect of laser irradiation of diode laser on healing of surgical wounds in rats]. / Vplyv laserového ziarenia diódového lasera na hojenie chirurgických rán u potkanov.

The aim of this work was to continue in previous study, which concerns biostimulation of skin wound healing evaluated after 24, 48, 120, 168 hours and so complete the chronological continuance of the process during the first seven days. Male, Sprague-Dawley rats (n=21) were used for the experiment. The rats were divided into 3 groups of 7 animals. In general anaesthesia (combination of xylazine, ketamine and tramadol) under aseptic condition two 3,5 cm long parallel skin incisions were performed on the left and right side of the rats spine and immediately sutured. The left wounds were daily stimulated with the diode laser (670 nm). The right wounds were not stimulated and served as control. The specimens of skin wounds were removed for histological evaluation 72, 96 and 144 hours after surgery. The biological specimens were stained with hematoxylin and eosin and histopathologically evaluated. In summary, in our histomorphological study of the influence of laser irradiation on primary wound healing evaluated after 72, 96 and 144 hours was concluded, that the healing of stimulated wounds was accelerated in comparison with controls. The histological evaluation showed earlier regress of inflammatory phase, faster finishing of reepithelization and acceleration in maturation phase. Presented experimental study completes the previous study and achieves the positive effect of biostimulation on all phases of skin wound healing in vivo.