Metformin-loaded chitosomes for treatment of malignant pleural mesothelioma - A rare thoracic cancer.

The purpose of this study was to design and evaluate chitosan dispersed lipid vesicles (chitosomes) as potential delivery carriers for repurposing metformin (Met) against malignant pleural mesothelioma. Chitosomes were prepared by directly hydrating the thin lipid film using chitosan solution as hydration medium, instead of using it as a coating agent. Developed chitosomes demonstrated spherical morphology, positive surface charge (~30 mV) and ~60% encapsulation efficiency. The calorimetric studies and X-ray diffraction pattern of Met-loaded chitosomes confirmed the successful encapsulation of Met inside the chitosome vesicles. Optimized chitosome formulation showed ~70% drug release in 72 h, displaying prolonged and controlled release of drug. Results demonstrated that Met encapsulated chitosomes possessed enhanced cellular internalization and improved cytotoxic potential. Our findings also supported inhibitory activity of chitosomes against metastatic property of pleural mesothelioma cells. The in-vitro tumor simulation studies further established anti-tumor activity of Met encapsulated chitosomes as supported by reduction in tumor volume and presence of minimal viable cells in tumor mass. The obtained results establish the effectiveness of chitosomes as delivery carrier for Met as treatment alternative for malignant pleural mesothelioma.

Long-Term Chronic Toxicity and Mesothelial Cell Reactions Induced by Potassium Octatitanate Fibers (TISMO) in the Left Thoracic Cavity in A/J Female Mice.

The present study was conducted to examine the chronic effects of potassium octatitanate fibers (trade name TISMO; chemical formula K2O·6TiO2) on the mouse lung and thoracic cavity. This method of infusion was employed to examine the direct effects of the fibers to the pleura. In the present study, 52- and 65-week experiments were employed to examine the long-term chronic effects after infusion of fiber-shaped TISMO into the thoracic cavities of A/J mice. Following this infusion, TISMO fibers were observed in the alveoli, indicating penetration through the visceral pleura. The additional histopathological detection of TISMO fibers in the liver, spleen, kidneys, ovary, heart, bone marrow, and brain of TISMO-infused mice indicated migration of the fibers out from the thoracic cavity. Atypical mesothelial cells with severe pleural proliferation were observed, but malignant mesotheliomas were not detected. This study demonstrated that intrathoracic infusion of TISMO fiber did not cause malignant mesothelioma but did cause severe chronic inflammation and proliferation of pleural mesothelial cells.

Anticoagulant rodenticides on our public and community lands: spatial distribution of exposure and poisoning of a rare forest carnivore.

Anticoagulant rodenticide (AR) poisoning has emerged as a significant concern for conservation and management of non-target wildlife. The purpose for these toxicants is to suppress pest populations in agricultural or urban settings. The potential of direct and indirect exposures and illicit use of ARs on public and community forest lands have recently raised concern for fishers (Martes pennanti), a candidate for listing under the federal Endangered Species Act in the Pacific states. In an investigation of threats to fisher population persistence in the two isolated California populations, we investigate the magnitude of this previously undocumented threat to fishers, we tested 58 carcasses for the presence and quantification of ARs, conducted spatial analysis of exposed fishers in an effort to identify potential point sources of AR, and identified fishers that died directly due to AR poisoning. We found 46 of 58 (79%) fishers exposed to an AR with 96% of those individuals having been exposed to one or more second-generation AR compounds. No spatial clustering of AR exposure was detected and the spatial distribution of exposure suggests that AR contamination is widespread within the fisher's range in California, which encompasses mostly public forest and park lands Additionally, we diagnosed four fisher deaths, including a lactating female, that were directly attributed to AR toxicosis and documented the first neonatal or milk transfer of an AR to an altricial fisher kit. These ARs, which some are acutely toxic, pose both a direct mortality or fitness risk to fishers, and a significant indirect risk to these isolated populations. Future research should be directed towards investigating risks to prey populations fishers are dependent on, exposure in other rare forest carnivores, and potential AR point sources such as illegal marijuana cultivation in the range of fishers on California public lands.

[Effect of herba schizonepetae volatile oil (STO) on activity of 5-lipoxygenase in rat thoracic cavity leukocytes].

OBJECTIVE: To investigate the effect of herba schizonepetae volatile oil (STO) on the activity of 5-lipoxygenase (5-LO), so as to elucidate its mechanisms of anti-inflammatory action which is related to the arachidonic acid (AA) metabolism. METHOD: Thoracic cavity leukocytes from the pleurisy model rat induced by injecting 1%-carrageenan into the pleural cavity were collected. Then 0. 4 mL cell suspension including 2 x 10(7) cells per millilitre were used as the reaction system in vitro. STO in different concentrations (final concentration 0.011, 0.022, 0.043, 0.087, 0.179, 0.255, 0.364 g x L(-1)), zileuton (final concentration 0.625 x 10(-3) g x L(-1)), and DMSO in the same volume were added into the reaction tube respectively. The reaction tubes were incubated at 37 degrees C for 20 min and CaCl2 (final concentration 2 mmol x L(-1)), MgCl2 (final concentration 0.5 mmol x L(-1)), exogenous AA (final concentration 200 micromol x L(-1)) and A23187 (final concentration 5 micromol x L(-1)) were added in turns during this period. The reaction tubes were mixed and continuously incubated at 37 degrees C for 30 min. After terminating reaction by adding methanol, the metabolites of 5-LO, leukotriene B4 (LTB4) and 5-hydroxy-6, 8, 11, 14-eicosatetraenoic acid (5-HETE), were extracted, separated and detected by means of RP-HPLC. RESULT: Compared with control group, STO significantly inhibited the biosynthesis of LTB4 and 5-HETE at final concentration between 0. 022 g x L(-1) and 0.364 g x L(-1) (P < 0.05 or 0.001) in dose dependence manner, and its IC50 value was 0.124 g x L(-1) and 0.142 g x L(-1) for LTB4 and 5-HETE, respectively. CONCLUSION: STO can inhibited the activity of 5-LO, which is an important enzyme of AA metabolism, in rat thoracic cavity leukocytes in a dose-dependent manner in vitro. It is suggested that the mechanism of anti-inflammatory action of STO is related to its inhibiting the activity of 5-LO and decreasing the level of major inflammatory mediators LTB4.

Effect of an intrathoracic injection of sodium hyaluronic acid on the prevention of pleural thickening in excess fluid of tuberculous thoracic cavity.

1. The aim of the present study was to evaluate the effect of a hyaluronate-based gel (HAbg) on the prevention of pleural thickening and adhesion in tuberculous pleural effusions (TPE). 2. Fifty-two patients who had accumulated a medium or large volume of tuberculous thoracic fluid, fluid being bound by fibre tissues and a pleura thickened more than 2 mm were divided randomly into two groups. All patients were all given standard treatments with antituberculous drugs. The HAbg was injected into the thoracic cavity in the treatment group (n = 27 patients), whereas normal saline was introduced into the thoracic cavity in the control group (n = 25 patients). Before and after HAbg injection, routine thoracic fluid examinations (including qualitative protein analysis, cell counts and classification of cell types) and protein quantification were performed. A chest radiograph and B-ultrasound were performed and pulmonary function was tested after 2 weeks and 3 months of thoracic fluid absorption. 3. The results show that patients who were treated with the HAbg had a significantly thinner pleura, a lower protein concentration and white blood cell count in the thoracic fluid and a higher forced expiratory volume in 1 s and forced vital capacity compared with patients in the control group. 4. Intrathoracic HAbg can prevent pleural thickening and improve lung function in patients who have a large amount of TPE.