Possibility of Taking an Offensive Stance in Extravasation Injury: Effects of Fat Injection in Vesicant (Doxorubicin) Induced Skin Necrosis Model in Rats.

INTRODUCTION: Extravasation injuries are one of the most feared complications of intravenous drug administration. The most common drugs associated with extravasation injury include chemotherapy agents and contrast media. Natural course of vesicant extravasation is discomfort, pain, swelling, inflammation, and ultimately skin ulceration. While diligence is the principle approach in prevention, immediate bed-side measures are as important in controlling the extent of tissue damage. Various options, either medical or interventional are next steps in treatment of the condition including antidotes, volume dilution, flushing, suction, hyperbaric oxygen therapy, and surgery. MATERIALS AND METHODS: 12 male Wistar albino rats were divided into two groups; one group received fat injections following subdermal doxorubicin infiltration in their right thighs, while other group received saline injection following subdermal doxorubicin infiltration in their right thighs for dilution. Left thighs of both groups were left untreated following subdermal doxorubicin infiltration. Total area of necrosis, as well as resultant epidermal thicknesses were assessed. Histological analyses were conducted using modified Verhofstad scoring system for comparison. RESULTS: Mean necrotic area was significantly smaller in the fat injection group compared to other groups. Median Verhofstad score was lesser in the fat injection group as well. Median epidermal thickness, on the other hand, was greater in the fat injection group. CONCLUSION: Injection of fat grafts following vesicant extravasation might be beneficial in preventing the progression of tissue damage, if employed early.

Preparation of Ethanol Extract of Propolis Loaded Niosome Formulation and Evaluation of Effects on Different Cancer Cell Lines.

Propolis is a candidate for cancer treatment with its activity against different tumor cells and, has a wide spectrum of biological and pharmacological activities due to the diversity of its components. In this study, antitumorigenic activities of ethanol extract of propolis (EEP) and ethanol extract of propolis loaded niosome (PLN) were compared using 2D and 3D cell culture. Niosome formulations were prepared by thin film hydration technique. Cell viability of EEP and PLN was analyzed on MCF7, A549, MDA-MB-231, SK-MEL, SK-BR-3, DU145 and L-929 cell lines using MTT assay. L929, MCF7 and A549 cells were cultured using the 3D petri dish technique and their spherical forms were obtained after 142 h. After 24 h, PLN and EEP application, cell viability analysis was performed on 3D cultures with WST assay. As a result, niosome formulations containing EEP showed higher activity than ethanol extract of propolis in cancer cells. While a slow decrease was observed in cell viability in EEP treated cancer cells, it was observed that the percentage viability rates decreased in a shorter time in PLN treated cancer cells. Also, PLN can be used as an anticancer activity drug such as Doxorubicin, but this is not the case for EEP.

Investigation of acute effects of topical Alpinia officinarum (galangal) treatment in experimental contact type burns and comparison with topical silver sulfadiazine treatment.

BACKGROUND: It was aimed to determine whether Alpinia officinarum (AO) (galangal), which has been regarded to be effective on wound healing, is healing on experimental contact type burns and compare its effects with silver sulfadiazine (SSD). METHODS: Thirty-five rats were divided into five groups of seven rats each group. Superficial second degree burns were formed by contacting a 1×1 cm copper tip which was kept at 100°C constant temperature to the three shaved areas on the back of rats without applying any pressure for 10 s. All groups were irrigated with a 100 cc saline solution for 2 min. Any procedure or treatment was not applied to Group I (Control). Group II (Burn Control) was only irrigated, Group III (SSD) was applied topical SSD 4 times, with 6-h intervals (at h 0, 6, 12 and 18), Group IV (Galangal) was applied topical AO 4 times, and Group V (Gel) was applied placebo topical material, used for the preparation of topical AO, 4 times. Wound healing findings were evaluated histopathologically. RESULTS: In the galangal group, it was found that collagen discoloration didn't penetrate into deep dermis compared to other groups; epidermis, hair follicles, and sebaceous glands remained protected compared to the burn control group, and there was a thicker layer of epidermis. It was found that the galangal group was the closest group to the control group histologically. In the galangal group, it was determined that the number of vessels and total hair follicles were significantly higher in the 8th h and 4th h respectively (p<0.05), while epidermal thickness and number of degenerated hair follicles were significantly higher in all hours compared to other three groups (p<0.05). It was determined that galangal group had the lowest scores in the evaluation of edema, polymorphonuclear leukocytes infiltration, collagen discoloration, injury of vessels, hair follicles and sebaceous glands in comparisons between groups and within groups' own processes. CONCLUSION: Administrating AO containing gel 4 times a day within the first 24 h is effective in the experimental contact type second degree burn model. It is significantly superior to SSD treatment, especially in the first 8 h of administration.

The healing effects of Hyperium perforatum (St. John's Wort) on experimental alkaline corrosive eosephageal and stomach burns.

BACKGROUND: The most frequent etiologic cause is alkaline substances. We investigated the protective effects of the plant St. John 's Wort (Hypericum perforatum). METHODS: We included 42 Wistar albino rats weighing between 200-300 grams and divided into six groups as Group 1: Control, Group 2: Burn+Saline (BS), Group 3: Burn+St. John's Wort (BSJW), Group 4: Burn+Plasebo (BP), Group 5: St. John's Wort (SJW), Group 6: Placebo (P). After 15 days of treatment, esophagus, stomach and liver tissue samples were derived by dissection for histopathologic and biochemical markers. The cytotoxic effects of formulation on fibroblasts is evaluated in vitro on human dermoblast fibroblast line (HDFa, Gibco Invitrogen cell culture, C-013-5C). RESULTS: The weight of the rats increased in Group 1, 3, 4, 6, decreased in Group 2 and did not change in Group 5. In the BSJW group, submucosal collagen accumulation, muscularis mucosa damage, tunica muscularis damage and collagen accumulation in esophagus were similar to the control group but lesser than BS and placebo group. In the stomach, mucosal damage, gastric gland dilatation, submucosal polymorphonuclear infiltration were similar to the control group and lesser than the BS group. The lethal concentration of SJW was 2.58 gr/mL. CONCLUSION: SJW substrate is effective in protecting the esophagus and stomach in mild to moderate alcali corrosive burns in the subacute period. We should keep in mind the protective effects of STW substrate in alkaline corrosive burns of the gastrointestinal system.

Inhibitor effect of paricalcitol in rat model of pentylenetetrazol-induced seizures.

Vitamin D has various systemic effects on bone metabolism, modulation of the immune system, stabilization of the cell membrane, oxidative stress, inflammation, apoptosis, and various other hormones. Differing from active vitamin D, paricalcitol is a relatively safe VDR agonist due to its relatively few side effects. This study has investigated the anticonvulsant effect of paricalcitol in convulsions induced by pentylenetetrazole (PTZ). 36 male Sprague-Dawley rats were divided randomly into two groups: 18 for EEG recording (PTZ 35 mg/kg) and 18 for behavioral studies (PTZ 70 mg/kg). Forty-five minutes before the PTZ injection, both groups of rats were given 5 and 10 µg/kg of paricalcitol i.p., respectively. Racine convulsion scores, first myoclonic jerk time, spike percentages, and antioxidant status were evaluated in the groups. Our results showed that the Racine's Convulsion Scale (RCS) score significantly dropped in the paricalcitol-treated group, analysis of the first myoclonic jerk (FMJ) latencies demonstrated a significantly longer latency in the paricalcitol-applied group, and spike percentages at EEG recordings significantly decreased with paricalcitol. Moreover, MDA levels were lower and SOD activity were higher in the 5 µg/kg paricalcitol group compared to the saline group; these results were more prominent in 10 µg/kg paricalcitol group. Our study has demonstrated that paricalcitol has protective effects on PTZ-induced convulsions. Based on the SOD and MDA levels in our study, these effects may result from the antioxidant characteristics of paricalcitol.

A contemporary review of molecular candidates for the development and treatment of childhood medulloblastoma.

INTRODUCTION: Medulloblastoma is the most common pediatric central nervous system tumor; however, the causes are not well established. There has been some emphasis on mutations in developmental pathways and their impact on tumor pathology in hereditary diseases, but, in order to better understand the nature of diseases like medulloblastoma, other mechanisms also require attention. PURPOSE: The purpose of this review is to provide an overview of the main genes involved in neurodevelopment, their downstream targets, and modulatory links by growth factors. Occurrence of pediatric brain tumors including medulloblastoma are mostly sporadic, but some hereditary diseases like Li-Fraumeni syndrome, Gorlin's syndrome, Turcot's syndrome, and Rubenstein-Tarbi syndrome are known to contribute their development as consequences of germline mutations at specific points: DNA-repairing gene Tp53 for Li-Fraumeni syndrome or Patch for Gorlin's, and apoptosis-related gene product adenomatous polyposis coli for Turcot's disease. CONCLUSION: Intracellular relations at molecular level and future therapeutics that specifically target the corresponding pathways should be well understood in order to prevent and cure childhood medulloblastoma.

Novel application of Eudragit RL and cholesteryl oleyl carbonate to thermo-sensitive drug delivery system.

The Eudragit RL 100 and propylene glycol (PG) membranes with and without cholesteryl oleyl carbonate (COC) were prepared by the solvent casting method to pioneer a novel application of a thermo-sensitive drug delivery system. After that, the properties of these membranes were investigated by thermal, scanning, and porosity studies. Drug permeation studies through all membranes were carried out using salbuthamol sulphate (SBS) at constant temperatures (25°C and 37°C), respectively. The permeability of SBS through the membranes with COC has been shown to be a discontinuous function of temperature, that is, their permeability increased steeply above the phase transition temperature (37°C) of the COC. The thermo-sensitive permeation mechanism for the membranes might be based on the structure change of the membranes caused by the phase transition, so that the membranes could absorb more water. Considering the high biological safety of Eudragit RL 100 and PG membranes with and without COC might be used to develop a novel thermo-sensitive drug delivery system.

Novel microparticle drug delivery systems based on chitosan and Eudragit® RSPM to enhance diltiazem hydrochloride release property.

The aim of this study was to enhance the release properties of diltiazem hydrochloride (diltiazem HCl) by using microparticle system. For this reason, microparticle drug delivery systems based on chitosan and Eudragit(®)RSPM were developed. The microparticles were prepared by using double-emulsion solvent extraction method and the mean sizes of microparticles were less than 120 µm. The in vitro drug release from microparticles was studied in simulated gastric (pH 1.2) and intestinal media (pH 7.4) than the results were evaluated by kinetically. In vitro diltiazem HCl release from microparticles showed good zero order kinetic. For the microparticles with chitosan, the release of diltiazem HCl at pH 1.2 could be effectively sustained, while the release of diltiazem HCl increased at pH 7.4 when compared to Eudragit(®)RSPM microparticles. The highest release percent obtained was 1:1 ratio of drug: polymer at pH 1.2 and 7.4. All results clearly suggest that the release properties of diltiazem HCl were improved by using microparticle systems especially which contain chitosan.

Clinical findings and gingival crevicular fluid prostaglandin E2 and interleukin-1-beta levels following initial periodontal treatment and short-term meloxicam administration.

OBJECTIVE: To evaluate the effects of adjunctive meloxicam administration on clinical periodontal measurements and gingival crevicular fluid (GCF) prostaglandin E(2) (PGE(2)) and interleukin-1-beta (IL-1beta) levels in chronic periodontitis. METHODS: Forty chronic periodontitis patients were randomized to receive either meloxicam 7.5 mg or placebo tablets for 10 days with scaling and root planing (SRP). GCF levels of PGE(2) and IL-1beta at baseline, day 10 of drug intake and 4 weeks after SRP were determined by enzyme-linked immunosorbent assay. Demographic, clinical periodontal data were analyzed using a repeated measures ANOVA and Bonferroni analysis. GCF PGE(2) and IL-1beta levels were compared between different evaluation times using the Friedman test. The Mann-Whitney test was used to compare biochemical data between the study groups. Pearson correlation analysis was used to relate clinical and biochemical data. RESULTS: Study groups showed significant reductions in all clinical periodontal measurements and GCF volume (p < 0.05). In both groups, IL-1beta was reduced significantly on day 10 and at week 4 compared with baseline (p < 0.01) without significant changes in PGE(2) levels (p > 0.05). No significant differences were found between study groups in GCF IL-1beta or PGE(2) levels (p > 0.05). CONCLUSION: Adjunctive meloxicam does not seem to provide additional improvement in clinical parameters or GCF PGE(2) and IL-1beta levels. Larger-scale studies may better clarify potential usage of anti-inflammatory agents in periodontal therapy.

Efficacy of sulphasalazine on lung histopathology in a murine model of chronic asthma.

Sulphasalazine is a specific inhibitor of nuclear factor kappa B (NF-kappa B) which plays a key role in asthma. To determine the impact of sulphasalazine in the treatment of chronic asthma, BALB/c mice were sensitized and challenged with ovalbumin. Mice with experimentally induced asthma in group I received saline, group II sulphasalazine 200 mg/kg, group III sulphasalazine 300 mg/kg, and group IV dexamethasone 1 mg/kg intraperitoneally once a day in the last 7 days of the challenge period. Histological findings of the airways were evaluated by light and electron microscopies. Dexamethasone and sulphasalazine in both doses significantly improved all airway histopathologic parameters of asthma except numbers of goblet cells. Both doses of sulphasalazine improved thicknesses of basement membrane better than dexamethasone. Dexamethasone reduced the number of mast cells better than sulphasalazine (200 mg/kg). Further studies are needed to evaluate the efficacy of sulphasalazine in the treatment of asthma.

In vitro studies on controlled-release cellulose acetate films for local delivery of chlorhexidine, indomethacin, and meloxicam.

BACKGROUND: Delivery of medications into periodontal pockets to suppress or eradicate the pathogenic microbiota or modulate the inflammatory response, thereby limiting periodontal tissue destruction, has attracted significant interest with the purpose of effective periodontal treatment. However, no study has previously attempted to develop a controlled-release formulation of anti-inflammatory agents to be used in the field of periodontology. The aim of the present study was to examine the in vitro release profile of chlorhexidine gluconate, indomethacin, and meloxicam from cellulose acetate films. METHODS: Cellulose acetate films containing chlorhexidine gluconate, indomethacin, and meloxicam were prepared and cut in a form to fit to the periodontal pocket anatomy. The release of active agents was studied in 10 ml artificial saliva at 37 degrees C. Apparatus Vibrax was used at 150 r.p.m. Determinations were carried out spectrophotometrically and the release profiles were plotted as a function of time. RESULTS: The formulations showed two different release patterns for a total observation period of approximately 120 h. When the formulations of the three active agents were compared, the release patterns of meloxicam and chlorhexidine gluconate were found to be similar, while the indomethacin-containing formulation exhibited the fastest release rate. CONCLUSIONS: As a conclusion, cellulose acetate may be a suitable inert material for obtaining a prolonged local release of various anti-inflammatory agents like meloxicam. Further in vitro and in vivo studies are required before starting clinical applications of these controlled-release formulations of anti-inflammatory agents.