Cyclosporin A and sanglifehrin A enhance chemotherapeutic effect of cisplatin in C6 glioma cells.

Glioma is the most common type of brain tumors in adults, and treatment of high-grade gliomas is still palliative. Studies to date have revealed only modest effect in attenuating growth of these tumors with single agent therapy, but combination treatment appears to be more effective. Cyclophilin A (CypA), a target of immunosuppressive drugs cyclosporin A (CsA) and sanglifehrin A (SFA), is an intracellular protein that has peptidyl-prolyl cis-trans isomerase (PPIase) enzymatic activity. Previously, we showed that overexpressed CypA induced chemoresistance in cancer cells. Here we provide evidence that combination of cisplatin with either CsA or SFA synergistically enhances apoptotic cell death in C6 glioma cells, compared with single agent treatment. Enhanced apoptotic cell death is a result of an increase in ROS generation and a decrease in intracellular glutathione levels. Consistently, CypA knockdown by siRNA also enhances cisplatin-induced apoptosis. Immunohistochemical analysis showed increased expression of CypA in human glioblastoma multiforme, but not in normal human astrocytes. CypA was also shown to be up-regulated in C6 glioma cells during hypoxia. In conclusion, CsA or SFA in combination with cisplatin synergistically enhances cisplatin-induced apoptosis in C6 glioma cells via inhibition of PPIase activity of CypA, indicating that development of new drugs that selectively inhibit the CypA PPIase activity without immune suppression may facilitate alleviation of chemoresistance in treatment of high-grade glioma.

Glycerol-based biorefinery for fuels and chemicals.

The rapidly expanding market for bioethanol and biodiesel is remarkably altering the cost and availability of glycerol. In general, approximately 10 pounds of crude glycerol are formed for every 100 pounds of biodiesel produced. Bioethanol process also generates glycerol up to 10% (w/w) of the total sugar consumed as a byproduct. Crude glycerol has thus been widely recognized as an attractive sustainable resource for chemical industries. Glycerol-based biorefinery is the microbial fermentation processes using inexpensive and readily available glycerol as the raw material to produce fuels and chemicals. A major challenge in fermentation of the low-grade crude glycerol is to obtain microbial strains tolerant to undesirable inhibitory components such as salts and organic solvents that present in crude glycerol. There have been several attempts to explore anaerobic microbial assimilation of glycerol using reconstructed microbial systems via microbial screening and metabolic pathway engineering. As a result, fuels as well as some high-value products were found to be produced by microbial fermentation of glycerol. This review describes biological processes using glycerol that produce fuels and chemicals including 1,3-propanediol, ethanol and organic acids.

Ephedrine reduces the pain from propofol injection.

UNLABELLED: One hundred seventy-six patients (ASA physical status I or II) presenting for elective surgery were randomly allocated into six study groups to compare the incidence of propofol-induced pain after pretreatment with different doses of ephedrine as compared with lidocaine. Patients in Group P (n = 30) received saline placebo; patients in Group L (n = 30) received 2% lidocaine 40 mg; patients received ephedrine 30 microg/kg (Group E30, n = 28), 70 microg/kg (Group E70, n = 30), 110 microg/kg (Group E110, n = 30), and 150 microg/kg (Group E150, n = 28), respectively, followed 30 s later by propofol 2.5 mg/kg. A blinded anesthesiologist asked the patient to evaluate the pain score (verbal rating scale and face pain scale). The incidence and intensity of pain was less in the lidocaine and ephedrine groups than in the placebo group (P < 0.01). Before tracheal intubation, the arterial blood pressure was decreased in the P and L groups, and after intubation, hemodynamics were increased in the E110 and E150 groups, respectively (P < 0.05). We concluded that pretreatment with a small dose of ephedrine (30 and 70 microg/kg) reduced the incidence and intensity of propofol-induced pain with a lesser decrease in arterial blood pressure than from propofol alone in lidocaine pretreatment. IMPLICATIONS: Propofol is a widely used IV anesthetic for the induction of anesthesia, but it often causes local pain when administered into peripheral veins. A small dose of ephedrine reduces the incidence and intensity of the pain without significant adverse hemodynamic effects during induction.