The effect of pregabalin - codeine combination on partial sciatic nerve ligation - induced peripheral mononeuropathy in rats.

The present study investigates the effects of pregabalin (PGB) and codeine (COD) combination on neuropathic hyperalgesia in an animal model of peripheral nerve injury represented by partial sciatic nerve ligation. Hot plate and analgesimeter tests were performed to evaluate the influence of PGB, COD and their combination on thermal and mechanical hyperalgesia in the hind paw with partial sciatic nerve ligation. Reactivity was evaluated by measuring the latency to withdrawal of the operated hind paw from the noxious heat and pressure stimulation. Nociceptive thresholds were evaluated before (baseline) and in the 1(st), 3(rd), 5(th) and 7(th) day after surgical procedure. The investigation demonstrates that the treatment with PGB attenuated partial sciatic nerve ligation development of thermal and mechanical hyperalgesia in rats operated hind paw. The oral administration, during 14 consecutive days of PGB-COD combination significantly reduced the degree of both thermal and mechanical hyperalgesia in the hind paw with partial sciatic nerve ligation. These results suggest that the association of PGB with COD exerted ameliorative effect on partial sciatic nerve ligation-induced neuropathic pain in rats.

New Nitric Oxide Donors With Therapeutic Potential.

Nitric oxide (NO), formerly known as the endothelium-derived relaxing factor, is a mediator with a key role in the body, both in the central nervous system and in periphery. NO is synthesized by several cell types, where it acts as an autocrine and paracrine signaling molecule. Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. In order to overcome the limitations linked with the use of nitric oxide and specially to increase the release of the radical in the targeted area, promising therapeutic strategies have been implemented, based on specific technologies which create releasing agents and vehicles for nitric oxide. Organic nitrites are the most known NO donor drugs, used especially in the treatment of cardiovascular diseases. In recent years, technological advances have allowed obtaining variations synthetic derivatives (such as diazeniumdiolates, S-nitrosothiols), which can generate NO in a controlled mode in the body and to chemically stabilize it; these compounds were studied with promising results in various animal models of vasospasm and pulmonary hypertension. Another high value therapeutic path is represented by the development of hybrid drugs (new nonsteroidal anti-inflammatory NO donor agents), with practical applications in inflammatory disorders accompanied by pain. Also, there is increasing evidence of the existence of NO donors with important antioxidant and hepatoprotective effects.

Imidazoline receptor antagonists idazoxan and efaroxan enhance locomotor functions in rats.

UNLABELLED: Discovered in 1984, imidazoline receptors (I1, I2, I3) are located centrally and peripherally being involved in various physiologic and pathophysiologic processes in the body. Experimental and clinical investigations have suggested the interrelations between imidazoline, adrenergic, dopaminergic, glutamatergic and opioid systems, which may explain the influence of different substances acting on imidazoline receptors in cognitive disorders, behavioral disturbances and motor diseases pathways. AIM: To investigate the effects of two imidazoline receptor antagonists on locomotor activity and endurance capacity in rats. MATERIAL AND METHODS: The experiment was carried out with white male Wistar rats (200-250 g) divided into 3 groups of 7 animals each, treated intraperitonealy with the same volume of solution as follows: Group I (Control): distilled water 0.3 ml/100 g body weight; Group II (IDZ): idazoxan 3 mg/kbw; Group III (EFR): efaroxan 1 mg/kbw. Exercise capacity was evaluated using a locomotor PanLAB treadmill test. The data were presented as mean +/- standard deviation and significance was tested by SPSS Statistics for Windows version 17.0 and ANOVA method. Experimental protocol was implemented according to recommendations of the Gr.T. Popa" University Committee for Research and Ethical Issues. RESULTS: Intraperitoneal administration of idazoxan and efarox- an resulted in a significant increase in running distance compared with the control group (p < 0.05). At the same time a reduction in the number and time of electric shocks delivered to motivate the animal to keep running was observed. In this experimental behavioral model the effects of idazoxan on the evaluated parameters were more intense than those of efaroxan. CONCLUSIONS: In our experimental conditions we demonstrated the ability of imidazoline receptor antagonists idazoxan and efaroxan to improve fatigue resistance during forced running in rats.

The effects of magnesium nanovesicle formulations on spatial memory performance in mice.

AIM: The study investigates the effects of magnesium nanovesicles on the memory processes performance in mice. MATERIALS AND METHODS: L-a-phosphatidylcholine was used to obtain nano formulations as lipid vesicles systems stabilized thereafter with chitosan. The experiment was carried out on white Swiss mice, divided into 3 groups of 7 animals each, treated orally 7 consecutive days: Group I (Control): 0.1 mL/10g distilled water; Group II (Mg): 1 mmol/kbw magnesium chloride; Group III (Mg-vesicles): 1 mmol/kbw magnesium nanovesicles. The spatial memory performance was assessed by recording spontaneous alternation behavior in Y-maze test. Each animal was placed at the end of one arm and allowed to move freely through the maze during a single 8 min session. Alternation was defined as a consecutive entry in three different arms. The alternation percentage was computed according to the formula: (number of alternations/total number of arm visits--2) x 100. Data were analyzed using SPSS 17.0 software. Experimental protocols were implemented according to the recommendations of the University Committee for Research and Ethical Issues. RESULTS: New carrier formulations entrapping magnesium chloride were designed: their mean size was 129.56 nm and the mean Zeta potential was +36.1 mV, indicating a moderate stability of the solution. Oral administration of magnesium vesicles resulted in a significant increase of spontaneous alternation percent in Y-maze test (p < 0.01), which suggests an improvement of short-term memory. CONCLUSIONS: Using magnesium chloride entrapped in lipid vesicles induced an enhancement of cognitive functions in mice especially by facilitation of learning extinction.

Effects of two serotoninergic agents on the behavioral manifestations in rats.

AIM: To investigate the effects of two serotonin receptor antagonists on spontaneous behavior in rats. MATERIAL AND METHOD: The experiment was carried out on white male Wistar rats (150-200g) divided into 3 groups of 6 animals each, treated intraperitoneally with the same volume of solution as follows: Group I (Control): saline solution 0.1 ml/10 g weight; Group II (SB-269970): SB-269970 1 mg/kbw; Group III (NAN-190): NAN-190 1 mg/kbw. The effects of serotonin receptor antagonists on the spontaneous psychomotor skills of rats were tested in Actimeter LE-8811 (PanLab). The data were presented as mean +/- standard deviation and significance was tested by SPSS Statistics for Windows version 17.0 and ANOVA method. The experimental protocol was implemented according to the guidelines for handling and use of experimental animals of the Research Ethics Committee of the Iasi "Grigore T. Popa" University and ethical standards of the European Community. RESULTS: The 5HT1 serotonin receptor antagonist NAN-190 determined a statistically significant reduction (p < 0.01) in both horizontal and vertical movements as compared with the control group, whereas the 5HT7 serotonin receptor antagonist SB269970 had no influence on rat behavioral manifestations. CONCLUSIONS: In our experimental conditions 1 mg/kbw NAN-190 decreased the total escape attempts, corresponding to a significant diminution of exploratory and self-maintenance spontaneous behavior in this experimental animal model. These manifestations may be correlated with the anxiolytic effect of 5HT1 serotonin receptor antagonist NAN-190 in rats. The administration of 5HT7 serotonin receptor antagonist SB-269970 did not alter the spontaneous activity in this behavioral experimental model in rats.

[Research on immune system response, skin and hepatic reactivity in laboratory animals after retro-auricular topical administration of two reactive textile dyes]. / Testarea pe animale de laborator a raspunsului sistemului imunitar, a reactivitatii cutanate si hepatice, dupa administrarea topica retroauriculara a doi coloranti reactivi textili.

AIM: To evaluate immune system response, skin and hepatic reactivity in Swiss mice after retro auricular local administration of two textile dyes. MATERIAL AND METHODS: On 3 groups of white Swiss mice: group I (Cibacron Yellow F-4G), group II (Cibacron Orange P-2R) and control group (DMSO dimethylsulfoxide), substances were applied on left retro auricular ear, in dose of 25 microL solution 10% in DMSO (the dyes were not soluble in water), once a day, for 7 days. After euthanasia, blood samples were taken to assay differential cell count, peripheral neutrophils activity (NBT test), serum opsonic capacity, peritoneal macrophages activity (phagocytic and bactericidal capacity), and activity of spleenic T-lymphocytes with rossetting capacity, and spleen cells forming Jerne plaques. There were taken skin from local application of dyes, retro auricular and later cervical nodes from left side and hepatic samples. RESULTS: Retro auricular and later cervical nodes mass increases after administration of textile dyes, compared to control group. Basophiles percentages were increased after administration of two dyes (stronger after yellow dye). Peripheral neutrophils activity was increased after administration of two dyes, especially after orange dye. Administration of the two dyes decreased serum opsonic capacity and peritoneal macrophages activity, but did not influenced the activity of spleenic T-lymphocytes with rossetting capacity and spleen cells forming Jerne plaques. There were significant skin and hepatic changes in microscopy. CONCLUSION: The studied dyes influenced the activity of immune system, increased skin and hepatic reactivity.

[Experimental study of immune reactivity in Swiss mice due to topical administration of three textile dyes]. / Studiu experimental pe soareci swiss privind modul de reactie a sistemului imunitar în urma administrarii topice a trei coloranti reactivi textili.

UNLABELLED: Reactive Red 183, Reactive Red 2 and Reactive Blue 204 (red dye, green dye and blue dye) are three reactive dyes frequently used in textile industry. In some atmospheric conditions ( high temperature, perspiration, pH values, UV/IR radiations), some quantities of these hydrolyzed dyes, could pass from textile clothes directly into the human skin. MATERIAL AND METHOD: There were used 4 groups of white Swiss mice (with similar weight and number of both sexes), control group and 3 groups, treated once daily with a retro-auricular application of different reactive dyes. After 14 days of treatment, blood samples were taken from retro-orbitary plexus to assess leukocyte count, phagocytic capacity of peripheral neutrophils, serum opsonic capacity, phagocyte capacity and bactericidal capacity of peritoneal macrophages, splenic T lymphocytes with rossetting capacity and spleen cells forming Jerne plaques. The retro-acuricular and latero-cervical nodes were weighted. RESULTS: Red dye did not influence the weight of the studied nodes, but determined statistically significant modifications on non-specific immune system parameters. Blue and grena dyes determined modifications of weight especially of retroauricular nodes. Grena dye determined important effects of non-specific immune system parameters (serum opsonic capacity, phagocyte capacity and bactericidal capacity of peritoneal macrophages). The blue dye did not determine a biological response. CONCLUSION: Red and green dye determined important effects on non-specific immune system parameters.