Effect of chronic lithium administration on endothelium-dependent relaxation of rat mesenteric bed: Role of nitric oxide

The mechanism of action of lithium, an effective treatment for bipolar disease, is still unknown. In this study, the mesenteric vascular beds of control rats and rats that were chronically treated with lithium were prepared by the McGregor method, and the mesenteric vascular bed vasorelaxation responses were examined. NADPH-diaphorase histochemistry was used to determine the activity of NOS (nitric oxide synthase) in mesenteric vascular beds. We demonstrated that ACh-induced vasorelaxation increased in the mesenteric vascular bed of rats treated with lithium. Acute No-nitro-L-arginine methyl ester (L-NAME) administration in the medium blocked ACh-induced vasorelaxation in the control group more effectively than in lithium-treated rats, while the vasorelaxant response to sodium nitroprusside, a NO donor, was not different between lithium-treated and control groups. Acute aminoguanidine administration blocked ACh-induced vasorelaxation of lithium-treated rats, but had no effect in the control rats. Furthermore, NOS activity, determined by NADPH-diaphorase staining, was significantly greater in the mesenteric vascular beds from chronic lithium-treated rats than in those from control rats. These data suggest that the enhanced ACh-induced endothelium-derived vasorelaxation in rat mesenteric bed from chronic lithium-treated rats might be associated with increased NOS activity, likely via iNOS. Simultaneous acute L-NAME and indomethacin administration suggests the possible upregulation of EDHF (endothelium-derived hyperpolarizing factor) in lithium-treated rats. © 2007 NRC

The value of integration of full container load, less than container load and air freight shipments in vendor–managed inventory systems

We address a long–haul transportation problem of delivering a set of products from a producer to a customer, where Full Container Load (FCL) shipments on one side and Less than Container Load (LCL) or Air Freight shipments on the other side are integrated. A Vendor-Managed Inventory (VMI) approach is used: a decision-maker has to find a periodic shipping policy that minimizes the sum of transportation cost and inventory cost, both at the producer and at the customer. This problem is defined at the tactical level implying that the initial inventory levels at the producer and at the customer are not data, but decision variables. For this problem we formulate a Mixed Integer Linear Programming model and prove its computational complexity. Furthermore, we introduce the concept of Value of Integration of FCL and LCL/Air Freight shipments and prove performance bounds to show that the integration of FCL and LCL/Air Freight shipments can lead to significant cost savings, both in the worst case and on average. Systematic computational experiments are finally carried out

Anti-diabetic effects of Amygdalus lycioides spach in streptozocin-induced diabetic rats

Diabetes mellitus is a group of metabolic disorders characterized by elevated blood sugar and abnormalities in insulin secretion and action. There are many anti-diabetic plants, which might supply useful sources for developing new medicines that can be used in treatment of diabetes mellitus. The primary objective of the present investigation is to evaluate the antidiabetic properties of the aerial parts of Amygdalus lycioides in streptozocin-induced diabetic rats. Sixty rats were divided into 6 groups: streptozocin-induced diabetic control, insulin-treated diabetic group, and four Amygdalus lycioides-treated diabetic groups (125, 250, 500, and 1000 mg/kg/day). After 2 weeks of plant extract administration, the effects of extracts on blood glucose, body weight, BUN, creatinine, total cholesterol, LDL, HDL, triglyceride, total protein, Na, K, and plasma enzymes (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase) were analyzed. The pancreas of rats was also stained for stereological studies. Phytochemical evaluation of this extract showed the presence of flavonoids and tannins compounds. Glucose serum levels and glucose tolerance test showed a decrease in treatment with Amygdalus lycioides (1000 mg/kg). Serum total cholesterol, LDL, triglyceride, creatinine and alkaline phosphatase levels were decreased significantly by the extract but aspartate aminotransferase found to be increased after treatment. The total number and numerical density of beta cells increased in the Amygdalus lycioides group (1000 mg/kg). It seems that Amygdalus lycioides may act as a potential drug to treat diabetes and its complications. However, more investigations should be done to more clarify these results. © 2018 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services

Administration of lithium and magnesium chloride inhibited tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice

Although morphine has an anticonvulsant effect in several animal models of seizures, its potential clinical application in epilepsy may be hindered by its adverse effects like opioid tolerance. The present study evaluated the development of tolerance to the anticonvulsant effect of morphine in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male Swiss mice. We also examined whether administration of either lithium chloride (LiCl) or magnesium chloride (MgCl2) was able to prevent the probable tolerance. Our data demonstrated that the anticonvulsant effect of a potent dose of morphine (1mg/kg) was abolished in chronic morphine-treated mice (mice administered the same dose of morphine intraperitoneally twice daily for 4days). Four days of pretreatment with low and noneffective doses of MgCl2 (2 and 5mg/kg) and LiCl (5mg/kg) inhibited the development of tolerance to the anticonvulsant effect of morphine (1mg/kg, ip). Moreover, a single acute injection of the aforementioned agents at the same doses reversed the expression of tolerance to the anticonvulsant effects of morphine (1mg/kg, ip). Chronic 17-day treatment with LiCl (600mg/L in drinking water) also inhibited the development of tolerance to the anticonvulsant effects of 1mg/kg morphine. These results demonstrate that the anticonvulsant effect of morphine is subject to tolerance after repeated administration. Both development and expression of tolerance are inhibited by either LiCl or MgCl2. As both LiCl and MgCl2 can modulate the function of N-methyl-d-aspartate (NMDA) receptors, we discuss how NMDA receptor functioning might be involved in the effects of LiCl and MgCl2 on the development of tolerance to the anticonvulsant effect of morphine. © 2010 Elsevier Inc

Evaluation of the best condition for ex vivo expansion of hematopoietic stem cells for the propose of cord blood transplantation

Introduction: Umbilical cord blood (CB) has been identified as a rich source for hematopoietic stem cells (HSCs), and has provided an alternative to bone marrow transplantation. The use of ex vivo expanded cells has been suggested as a possible means to accelerate the speed of engraftment in cord blood (CB) transplantation. The main aim of our study is to find the best culture media and condition to increase number of CD34 +/CD38 - hematopoietic stem cells in cord blood for transplantation. Material and Methods: Mononuclear cells (MNCs) were seperated from cord blood and cultured in RPMI1640 with 10 fetal calf serum (FCS) or 10 cord blood plasma (CBP) or serum free media (SF). Culture media contained 50ng/ml of lnterlukin 6 (IL6), IL3, Thrombopoietin (TPO) Stem cell factor (SCF) and flt3-ligand. Cells were cultured for two weeks and number of CD34 +/CD38 - cells and total MNCs measured at days 0, 7 and 14. Results: At 14 days culture mean fold of expansion of CD34 + and CD34 +/CD38 - cells was 20.4 and 57.4 for FCS, 5.6 and 10.3 for SF and 10.8 and 4.7 for CBP culture media. Conclusion: Due to efficacy and predictability of SF media for cell expansion and because of its better safety for allergic reactions and microbial contamination (in comparison to animal products containing media) and enough expansion for clinical applications, we suggest that SF media is better than CBP or SF from clinical points of view