Decreased therapeutic effects of noscapine combined with imatinib mesylate on human glioblastoma in vitro and the effect of midkine

<p>Abstract</p> <p>Background</p> <p>Glioblastoma (GBM) develops resistance to the advances in chemotherapy leading to poor prognosis and life quality. Consequently, new treatment modalities are needed. Our aims were to investigate the effects of combined noscapine (NOS) and imatinib mesylate (IM) on human GBM <it>in vitro </it>and the role of midkine (MK) in this new combination treatment.</p> <p>Methods</p> <p>Monolayer and spheroid cultures of T98G human GBM cell line were used to evaluate the effects of IM (10 μM), Nos (10 μM) and their combination on cell proliferation and apoptotic indexes, cell cycle, the levels of antiapoptotic MK, MRP-1, p170, PFGFR-α, EGFR, bcl-2 proteins, apoptotic caspase-3 levels, morphology (SEM) and ultrastructure (TEM) for 72 hrs. Results were statistically analyzed using the Student's t-test.</p> <p>Results</p> <p>The combination group induced highest decrease in cell proliferation and apoptotic indexes, caspase-3 levels, MRP-1 and PDGFR-α levels. The decrease in p170 levels were lower than IM but higher that NOS. The highest increases were in EGFR, MK, bcl-2 and cAMP levels in the combination group. The G0+G1 cell cycle arrest at the end of 72^ndhr was the lowest in the combination group. Apoptotic appearence was observed rarely both in the morphologic and ultrastructural evaluation of the combination group. In addition, autophagic vacuoles which were frequently observed in the IM group were observed rarely.</p> <p>Conclusions</p> <p>The combination of Nos with IM showed antagonist effect in T98G human GBM cells in vitro. This antagonist effect was correlated highly with MK levels. The effects of NOS on MRP-1, MK and receptor tyrosine kinase levels were firstly demonstrated in our report. In addition, we proposed that MK is one of the modulator in the switch of autophagy to cell death or survival/resistance.</p

Use of medetomidine, midazolam, ketamine and sevoflurane as an anesthetic protocol for domestic chickens

Changes in physiological and biochemical parameters after administration of medetomidine (MED), midazolam (MID), ketamine (KET) and a 2% of the inhalation anesthetic sevoflurane (SEVO), were investigated in domestic chickens. The anesthetic protocol began with a simultaneous intrapectoral injection (IP) of MED (50 mu g/kg) and MID (0.5 mg/kg), followed by IP administration of 25 mg/kg of KET 10 min later. Anesthesia was then maintained for 30 min by 2% SEVO (with a 500 ml/min oxygen flow), using an Ayres T piece device. Heart and respiratory rates, cloacal temperature, reflex response and electrocardiogram (ECG) parameters were recorded at time zero (T0) before anesthesia (BA, baseline values), at time of MED + MID administration (T1), at time of ketamine injection (T2), 30 min after the start of SEVO inhalation (T3) and at recovery. Blood was also drawn at T0 and T3 to assess albumin, creatinine, glucose and liver enzyme concentrations. Cloacal temperature, heart and respiratory rates differed from baseline values at all time intervals during anesthesia (p < 0.05). Heart rate decreased following the MED + MID injection (at T1, T2 and T3), and partially recovered by the reanimation period. Reflex response also differed between time 0 and all anesthesia time points (p < 0.05). Mean amplitude of the P wave of the ECG was increased during MED + MID (T1) and KET (T2) anesthesia. The mean ST interval showed a large increase at T1, which was maintained throughout anesthesia (p < 0.05). Albumin, glucose and the ALT enzyme decreased between T0 and T3. In conclusion, the use of MED + MID + KET and SEVO as an anesthetic combination altered card ioresp ratory and biochemical parameters of chickens, but no life-threatening effects were observed as a result of these changes. Hence, this drug combination can be adequately used as an anesthesia protocol in chickens

Decreased therapeutic effects of noscapine combined with imatinib mesylate on human glioblastoma in vitro and the effect of midkine

Background: Glioblastoma (GBM) develops resistance to the advances in chemotherapy leading to poor prognosis and life quality. Consequently, new treatment modalities are needed. Our aims were to investigate the effects of combined noscapine (NOS) and imatinib mesylate (IM) on human GBM in vitro and the role of midkine (MK) in this new combination treatment