Mihai Nechifor

Magnesium involvement in pain

mrh.2011.0296 Auteur(s) : Mihai Nechifor mnechif@yahoo.com Department of pharmacology, Gr.xa0T.xa0Popa University of Medicine and Pharmacy, Iasi, Romania Correspondence. Mihai Nechifor, Department of Pharmacology, Gr.xa0T.xa0Popa University of Medicine and Pharmacy, Universitatii 16, Iasi 700115 Romania, Tel. 0040-232-220875, 0040-744-50-8642. The very interesting paper of Pickering et al. [1] raises the issue of the involvement of this cation in different types of pain. Pain is very [...]

The influence of magnesium on morphine-induced stimulation of the reward system

The present study was designed to assess the influence of magnesium (Mg) as MgCl(2) (10 or 40 mg/kg b.wt/day i.p.) and of its interaction with morphine on the reward system (RS) in Wistar rats. For this purpose, we evaluated conditioning place preference on a 12 day experiment schedule. Our data show that MgCl(2) (10 mg/kg b.wt/day) has moderate but significant effects on stimulating RS (increasing the time spent in associated conditioned compartment) (327.75 +/- 11 s in the Mg (10 mg/kg b.wt) group vs 295.2 +/- 8 s in the control (saline) group, p < 0.05) but not at higher Mg doses (40 mg/kg b.wt/day). We tested the influence of MgCl(2) (10 mg/kg b.wt./day i.p.) upon naloxone (2 mg/kg b.wt/ i.p.)-induced place aversion. Administrated alone, naloxone has an aversive effect on place preference. MgCl(2) (10 mg/kg b.wt/day i.p.) has a significantly decreased aversive effect of naloxone (280.7 +/- 37 s in naloxone + MgCl(2) (10 mg/kg b.wt) group vs 189 +/- 21 s in naloxone group, p < 0.05). MgCl(2) at both tested doses, added to morphine (3 mg/kg b.wt/day i.p), decreased the acquisition of morphine-induced place preference (262.2 +/- 17 s) in morphine + MgCl(2) (40 mg/kg b.wt) group vs 462.15 +/- 28 s in morphine group, p < 0.05). MgCl(2), 10 mg/kg b.wt/day i.p. decreased both morphine-induced place preference and naloxone-induced place aversion.

Effects of liposome-entrapped platelet-activating factor in the isolated rat trachea

The effects of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine)-filled liposomes upon rat tracheal rings in vitro were examined. The capture of liposomes by the smooth muscle cells of the isolated tracheal rings as well as the release of their content into the cytoplasm was shown by using Evans blue (5 x 10(-4) M)-loaded liposomes. Administration of PAF (10(-3) M)-filled liposomes contracted the preparations, in contrast with extracellular administration of PAF and control liposomes, which had no effect. Administration during the plateau or pretreatment with liposomes containing BN 52021 (3-t-butylhexahydro-4,7b-trihydroxy-8-methyl-9H-1,7a-epoxymethano- 1H,6aH- cyclopenta[c]furo(2,3-b)furo[3,2:3,4]cyclopental [1,2-d]furan-5,9,12(4H)-trione) ((10(-3) M, a selective PAF receptor antagonist) or heparin (5 x 10(-5) M) blocked this contraction. BN 52021 and heparin, not entrapped in liposomes, had no such effect. Our data suggest an intervention of PAF in the mechanisms of contraction of tracheal smooth muscle, involving a direct or indirect intervention (intracellular receptors for PAF cannot be excluded). At the same time, the rat trachea contraction induced by PAF-loaded liposomes could be linked to the PtdIns(1,4,5)P3-dependent Ca2+ channels from the endoplasmic reticulum and/or to the interaction with G proteins, as shown by the blocking effects of heparin-containing liposomes.

Hypolipidemic effect of a pro-drug containing nicotinic acid in rats

We studied the release of nicotinic acid from a macromolecular pro-drug containing niacin bound to a polymeric support of dextran. Using a modified High-performance Liquid Chromatography (HPLC) method to provide an improved separation between nicotinic acid and its metabolites, we compared the plasma levels of nicotinic acid 24 h after administration of the pro-drug or a similar dose of unbound nicotinic acid to rats. Nicotinic acid exerts a number of pharmacological activities among which is the hypolipidemic effect. To determine the hypolipidemic effect of the pro-drug, we measured the triglyceride levels and examined the correlation with the plasma levels of nicotinic acid.Starting 6 h after administration of the pro-drug, the plasma levels of nicotinic acid were high enough to cause a decrease in the triglyceride level. These results suggest that nicotinic acid was gradually released from the polymeric support, leading to the sustained presence of the active substance and, therefore, a reduction in the level of triglycerides.

Chromium picolinate reduces morphine-dependence in rats, while increasing brain serotonin levels

Chromium is an essential trace element with anti-diabetic and anti-depressant effect; the latter is considered related to chromium properties of increasing brain serotonin. Cr3+ salts were shown to improve some forced swimming-parameters and to induce rewarding effects, which are additive to those of morphine, but Cr effect on addictive processes has not been tested.nnnAIMnThe present study aimed to assess chromium picolinate (CrPi) influence on morphine-dependence in rats.nnnMATHERIAL AND METHODSnWe used five groups of 10 rats. Groups 1 and 2 (controls) received saline, respectively CrPi, 0.01u202fmg/kg/day, for 10 days. In groups 3, 4 and 5 dependence was induced with progressively-increased morphine doses (from 5 - day 1-90u202fmg/kg/day - day 10, s.c.). Group 3 received only morphine, while groups 4 and 5 received CrPi, i.p., 10 and respectively 5u202fμg/kg/day, during the 10 days of dependence induction. On day 11, groups 3, 4, and 5 were administered 90u202fmg/kg morphine, and, 2u202fh later, all rats received naloxone, 2u202fmg/kg s.c., to precipitate withdrawal. We compared withdrawal intensity in group 3 vs. groups 4 and 5, assessing both individual symptoms and Gellert-Holtzman global withdrawal score. Upon rats sacrifice at the end of the experiments, brain serotonin (5HT) in certain areas and serum Cr were assessed.nnnRESULTSnSome withdrawal signs were unequally influenced by CrPi: compulsive mastication was reduced by both CrPi doses (pu202f<u202f0.05), while teeth chattering and grooming were significantly reduced only by the higher dose (pu202f<u202f0.05). Withdrawal score was reduced by both CrPi doses: from 132.4u202f±u202f9.87 - group 3 to 122.2u202f±u202f6.47 - group 4 (pu202f<u202f0.01 vs. group 3) and 124.1u202f±u202f8.41 - group 5 (pu202f<u202f0.05 vs. group 3). CrPi reduction of withdrawal is accompanied by increased brain 5u202fHu202fT, mainly in the prefrontal cortex (646.3u202f±u202f8.51 - group 3 vs. 661.5u202f±u202f14.63 - group 4, pu202f<u202f0.01 and 660.7u202f±u202f14.01u202fpg/mg tissue - group 5, pu202f<u202f0.05 vs. group 3). CrPi also increases brain 5u202fHu202fT in non-dependent rats (prefrontal cortex: 541.6u202f±u202f31.80, group 1 and 565.5u202f±u202f16. 46u202fpg/mg tissue, group 2, pu202f<u202f0.05). Administration of CrPi determined a dose-dependent increase of serum Cr.nnnCONCLUSIONSnOur study evidenced a slight, but significant reduction of morphine dependence in rats induced by chromium picolinate, accompanied by increased brain serotonin. This might be considered a supplementary evidence for chromium anti-depressant effect and its serotonin-mediated mechanisms.

Effects of PGF2alpha analogues in experimental morphine-induced pharmacodependence

Prostaglandines and other eicosanoids are involved in a multitude of normal and pathological processes at CNS level.

The influence of some analogues of PGF1 alpha and PGF2 alpha on ethanol experimental hepatopathy on rats

10, SGPT = 41 413 U/L. The improvement of U/S imaging was in 18 out of 21 pts (85.7%). 4) No serious side effect was observed nor any increase of the levels of aminotransferases in any pts during treatment. Conclusion: 1) Orlistate appears to be more effective than omega 3 fatty acids and atorvastatine in biochemical (p 0.10) in biochemical and U/S improvement (p > 0.10) in comparison to omega 3 fatty acids. 3) Furthermore investigation and after biopsy evaluation is demanded to prove the efficacy of every one drug in the treatment of NASH.