Novel modified carbon nanotubes as a selective sorbent for preconcentration and determination of trace copper ions in fruit samples.

In this work, multiwalled carbon nanotubes were reacted with N-[3-(triet-hoxysilyl)propyl]isonicotinamide to prepare pyridine-functionalized carbon nanotubes. This novel sorbent was characterized by infrared spectroscopy, thermal and elemental analysis, and scanning electron microscopy. Functionalized carbon nanotubes were applied for the preconcentration and determination of copper ions using flame atomic absorption spectrometry. Various parameters such as sample pH, flow rate, eluent type and concentration, and its volume were optimized. Under optimal experimental conditions, the limit of detection, the relative standard deviation, and the recovery of the method were 0.65 ng/mL, 3.2% and 99.4%, respectively. After validating the method using standard reference materials, the new sorbent was applied for the extraction and determination of trace copper(II) ions in fruit samples.

Involvement of amlodipine, diazoxide, and glibenclamide in development of morphine tolerance in mice.

In this study, the effects of the calcium channel blocker (amlodipine), potassium channel opener (diazoxide), and potassium channel blocker (glibenclamide) on the development of morphine-induced tolerance in the formalin test was investigated. During development of tolerance to morphine, intraperitoneal (i.p.) administration of different doses of amlodipine (5, 7.5 and 10 mg/kg) or diazoxide (1, 5 and 10 mg/kg) in combination with morphine (20 and 30 mg/kg) increased tolerance in the first and second phase of the test. However, glibenclamide (2.5, 5, and 10 mg/kg) decreased morphine tolerance in the second phase of formalin test. It is concluded that calcium and potassium channel mechanisms may be involved in the morphine tolerance.

Involvement of glucose and ATP-sensitive potassium (K+) channels on morphine-induced conditioned place preference.

In the present study, the effects of glucose and ATP-sensitive K+ channel compounds on the acquisition of morphine-induced place preference in male mice were investigated. Subcutaneous administration of different doses of morphine (2.5-7.5 mg/kg) produced a dose-dependent conditioned place preference. With a 3-day conditioning schedule, it was found that glucose (100, 200, 500 and 1000 mg/kg), diazoxide (15, 30 and 60 mg/kg) or glibenclamide (3, 6 and 12 mg/kg) did not produce significant place preference or place aversion. Intraperitoneal administration of the glucose (1000 mg/kg) or glibenclamide (6 and 12 mg/kg) with a lower dose of morphine (0.5 mg/kg) elicited the significant conditioned place preference. The response of glibenclamide (6 mg/kg) was reversed by diazoxide (15, 30 and 60 mg/kg). Drug injections had no effects on locomotor activity during the test sessions. It is concluded that glucose and the ATP-sensitive K+ channel may play an active role in morphine reward.

Epothilone-paclitaxel resistant leukemic cells CEM/dEpoB300 are sensitive to albendazole: Involvement of apoptotic pathways.

Altered or deficient activation of apoptosis signalling pathways may contribute to drug resistance. Here, we assess the role of apoptotic mediators in eliciting an anti-proliferative response to paclitaxel (PTX) in a T cell acute lymphoblastic leukemia (ALL) cell line CEM and its epothilone-paclitaxel resistant sub-line CEM/dEpoB300. Furthermore, the cellular response to PTX was compared to those elicited by cells in response to treatment with albendazole (ABZ; a microtubule depolymerizing agent). In cell proliferation studies, CEM cells were sensitive to both PTX and ABZ, while the CEM/dEpoB300 cells were highly resistant to PTX (IC(50) 2.86 nM versus 30.26 nM, respectively). In contrast, the resistant cells showed a 2-fold increase in sensitivity to ABZ (0.32 microM in CEM compared to 0.16 microM in CEM/dEpoB300). Analysis of caspase-3 activity and cytochrome c release in response to PTX or ABZ treatment (24, 48 and 72 h) revealed that, compared to the parent cells, the resistant cells have diminished response to PTX and enhanced response to ABZ. A similar pattern was observed for the pro-apoptotic protein Bax. Levels of the anti-apoptotic protein Bcl-2 was highly elevated in CEM/dEpoB300 cells and in these cells, ABZ was more effective in lowering the Bcl-2 levels than PTX. Similarly, ABZ treatment led to profound down regulation of the Mcl-1 protein. These results reveal for the first time, the changes in apoptotic mediators following development of resistance to PTX in an ALL cell and the significantly increased sensitivity of these PTX resistant cells to ABZ.

Influence of ATP-sensitive potassium channels on lithium state-dependent memory of passive avoidance in mice.

The effects of ATP-sensitive potassium channels on lithium induced state-dependent memory of passive avoidance task were examined in mice. The pre-training (5 mg/kg) and pre-test (5 mg/kg) injection of lithium impaired memory retrieval on the test day. Impairment of pre-training lithium was restored by pre-test administration of lithium (5 mg/kg), diazoxide, an ATP-sensitive potassium channel opener, (15, 30 and 60 mg/kg) or glibenclamide, an ATP-sensitive potassium channel blocker, (6 and 18 mg/kg). Pre-test administration of inactive doses of lithium (2.5 and 10 mg/kg) plus lower and inactive dose of glibenclamide (2 mg/kg) or diazoxide (1.5 mg/kg) also reversed the amnesia induced by pre-training lithium (5 mg/kg). In conclusion, the ATP-sensitive potassium channel opener or blocker not only mimicked the effect of lithium in state-dependent learning in the absence of lithium on the test day, but also potentiated the effect of low dose of lithium in restoration of memory. Therefore, ATP-sensitive potassium channels may have a modulatory influence on lithium response.

Morphine state-dependent learning sensitization and interaction with nitric oxide.

In the present study, the effects of nitric oxide (NO) precursor L-arginine and L-NAME, a potent inhibitor of NO synthase (NOS), on the expression of sensitization of morphine were investigated. Pre-training administration of morphine (5 mg/kg) impaired memory retrieval compared to pre-training saline-treated animals. Amnesia due to pre-training morphine (5 mg/kg) was restored by pre-test morphine (5 mg/kg). The retrieval impairment was also inhibited in mice which had received once-daily injections of morphine (20 and 30 mg/kg, s.c.) for 3 days, followed by 5 days of no drug treatment before training (in order to induce morphine sensitization). Administration of L-arginine (60 mg/kg/day - 3 days) or L-NAME (20 mg/kg/day - 3 days) before training did not alter morphine state dependency. During acquisition of sensitization, administration of L-arginine (60 mg/kg) 20 min before morphine (10 mg/kg/day, for 3 days) increased, while injection of L-NAME (20 mg/kg) 20 min before morphine (30 mg/kg/day, for 3 days) decreased morphine state dependency. It is concluded that NO is involved in the morphine-induced sensitization.

Influence of morphine- or apomorphine-induced sensitization on histamine state-dependent learning in the step-down passive avoidance test.

Effects of morphine- or apomorphine-induced sensitization on histamine state-dependent memory of passive avoidance task were examined in mice. Pre-training intracerebroventricular (i.c.v.) administration of histamine (20 microg/mouse) decreased the learning of a one-trial passive avoidance task. Pre-test administration of histamine (10 and 20 microg/mouse) reversed amnesia induced by pre-training of histamine, with maximum response at 20 microg/mouse. Pre-training histamine-induced amnesia was also reversed in morphine- or apomorphine-sensitized mice that had previously received once daily injections of morphine (20 and 30 mg/kg) or apomorphine (0.5 and 1 mg/kg) for 3 days. The reversion of histamine-induced amnesia in morphine-sensitized mice was decreased by once daily administration of naloxone (0.5 and 1 mg/kg), SCH 23390 (0.05 and 0.1 mg/kg) or sulpiride (25, 50 and 100 mg/kg) prior to injection of morphine (30 mg/kg/day, 3 days). Furthermore, once daily administration of sulpiride (50 and 100 mg/kg) but not SCH 23390 (0.01, 0.05 and 0.1 mg/kg) prior to apomorphine (1 mg/kg, for 3 days) decreased the reversion of pre-training histamine-induced amnesia by apomorphine. The results suggest that apomorphine or morphine sensitization affects the impairment of memory induced by histamine and thus it is postulated that opioid and dopamine receptors may play an important role in this effect.

Influence of intracerebroventricular administration of dopaminergic drugs on morphine state-dependent memory in the step-down passive avoidance test.

The effects of dopaminergic drugs on morphine state-dependent memory of passive avoidance task were examined in mice. Pre-training administration of morphine (5mg/kg) led to state-dependent learning with impaired memory retrieval on the test day which was reversed by pre-test administration of the same dose of the opiate. The pre-test intracerebroventricular (i.c.v.) administration of the dopamine D1 receptor agonist (SKF38393), dopamine D2 receptor agonist (quinpirole) and dopamine D2 receptor antagonist (sulpiride) not only reversed the effect of pre-training morphine treatment, but also increased this action of the drug. Furthermore, the pre-test i.c.v. administration of dopamine D1 receptor antagonist (SCH23390) prevented the restoration of memory by morphine. In conclusion, the morphine-induced recovery of memory, on the test day, seems to be induced, at least in part, through dopamine receptors.

Influence of intracerebroventricular administration of cannabinergic drugs on morphine state-dependent memory in the step-down passive avoidance test.

The effects of cannabinergic drugs on morphine state-dependent memory of passive avoidance task were examined in mice. Pre-training (0.25, 0.5 and 5 mg/kg) and post-training (5 mg/kg) administration of morphine impaired memory retrieval on the test day. Impairment of memory retrieval by morphine (5 mg/kg) on the test day was reversed by pre-test administration of the same dose of the opioid. The pre-test intracerebroventricular administration of the cannabinoid CB1/CB2 receptor agonist (WIN55,212-2) (0.75 and 1 microg/mouse) not only mimicked the effect of pre-test morphine treatment, but also increased this action of the opioid. Furthermore, the pre-test intracerebroventricular administration of CB1 receptor antagonist (AM251) (20 and 100 ng/mouse) prevented the restoration of memory by morphine. Pre-training administration of WIN55,212-2 (1 microg/mouse) led to state-dependent learning with impaired memory retrieval on the test day as well, which was reversed by pre-test administration of the drug (0.5, 0.75 and 1 microg/mouse) or morphine (1 and 5 mg/kg). Restoration of impairment induced by WIN55,212-2 was decreased by both the opioid receptor antagonists, naloxone (0.01 microg/mouse) and AM251 (20 and 100 ng/mouse). In conclusion, the improvement of memory retrieval by morphine treatment on the test day seems to be induced, at least in part, by the cannabinoid CB1 receptors.

Effects of intracerebroventricular administration of ultra low doses of histaminergic drugs on morphine state-dependent memory of passive avoidance in mice.

The effects of intracerebroventricular (i.c.v.) administration of ultra low doses (ULDs) of histamine, clobenpropit and pyrilamine are studied on morphine state-dependent (STD) memory in mice. Although pre-test administration of different doses of histamine and clobenpropit showed no effect on impairment of memory induced by pre-training morphine, when the above drugs were co-administered with morphine, they inhibited the restoration of memory by morphine. These effects were opposite to microgram doses of the same drugs.

Cross state-dependent retrieval between histamine and lithium.

Histamine and lithium state-dependent (StD) retrieval of passive avoidance task and their interactions was examined in mice. The pre-training or pre-test intracerebroventricular (i.c.v.) injection of histamine (20 microg/mouse) impaired retrieval when it was tested 24 h later. In the animals, in which retrieval was impaired due to histamine pre-training administration, pre-test administration of histamine, with the same dose, restored retrieval. The H1 blocker, pyrilamine (20 microg/mouse, i.c.v.), but not the H(2) blocker; ranitidine prevented the restoration of retrieval by pre-test histamine. The pre-training (5 and 10 mg/kg) or pre-test (5 mg/kg) injection of lithium also impaired retrieval, when it was tested 24 h later. In the animals that received lithium (5 mg/kg) or histamine (20 microg/mouse) as pre-training treatment, administration of histamine, clobenpropit or lithium, respectively, resulted in restoration of memory retrieval. Neither pyrilamine nor ranitidine prevented the restoration of retrieval by pre-test lithium. In conclusion, histamine or lithium can induce state-dependent retrieval and a cross-StD exists between these drugs, which may be mediated through the inositol pathway.

Influence of intracerebroventricular administration of histaminergic drugs on morphine state-dependent memory in the step-down passive avoidance test.

The effects of histaminergic drugs on morphine state-dependent memory of a passive avoidance task were examined in mice. Pre-training administration of morphine (5 mg/kg) led to state-dependent learning with impaired memory recall on the test day which was reversed by pre-test administration of the same dose of the opioid. The pre-test intracerebroventricular (i.c.v.) administration of the H(1) blocker (pyrilamine) prevented the restoration of memory by morphine. The H(2) blocker (ranitidine) was ineffective in this regard and the H(3) blocker (clobenpropit) potentiated the effect of morphine on memory recall. The pre-test i.c.v. administration of histamine alone (5, 10, and 20 microg/mouse) not only mimicked the effect of pre-test morphine treatment, but also increased this action of the opioid. The effect of histamine on memory recall was not changed by the pre-test administration of mu-opioid receptor antagonist, naloxone. In conclusion, the improvement of memory recall by morphine treatment, on the test day, seems to be, at least in part, through the release of histamine followed by the stimulation of H(1) receptors. Histamine by itself, when administered on the test day, mimicked morphine-induced memory improvement by a mechanism independent of the mu-opioid receptors.

The effect of furosemide infusion on serum epidermal growth factor concentration after acute lung injury.

Acute lung injury and its more severe form, acute respiratory distress syndrome, are clinical syndromes of progressive hypoxemia and ventilation-perfusion mismatch with decreasing pulmonary compliance in the absence of congestive heart failure. Epidermal growth factor is involved in the pathogenesis of airway inflammation as well as a proinflammatory effect in other tissues. Furosemide has been shown to improve pulmonary gas exchange and intrapulmonary shunt by a nondiuretic mechanism in animal models of acute respiratory distress syndrome. The current study was undertaken to clarify whether furosemide attenuates the inflammatory response by changing the epidermal growth factor level in patients with acute lung injury. A prospective, randomized clinical trial involving 30 patients with acute lung injury was designed and conducted over 7 days. The measured outcomes included hemodynamics, acute physiology and chronic health evaluation (APACHE II) scores, and oxygenation. The serum specimens were analyzed with enzyme-linked immunoassay (ELISA) for epidermal growth factor at baseline, then 3 and 7 days after acute lung injury. The ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FIO2) improved in the furosemide-treated group within 24 hours (from 180 to 264; P = .01). The mean arterial pressure and heart rate was greater in this group than in the control group (that received no furosemide) on day 7 (P = .027). The mean arterial pressure increased and the heart rate decreased over time in the treatment group, but not significantly. Serum epidermal growth factor levels also were not significantly different between the furosemide treatment group and the control group (P > .05). Continuous furosemide infusion improves oxygenation and hemodynamics in patients with acute lung injury, but not through a change in the serum epidermal growth factor level. Further study is needed to determine the exact mechanism of furosemide action in patients with acute lung injury and acute respiratory distress syndrome.