Iranian Journal of Basic Medical Sciences
Year:2002 | Volume:5 | Issue:3 (15)|Papers Count:9

A major role of insulin in mammals is the regulation of glucose homeostasis by modulating glucose production in the liver and glucose utilization in other tissues. Liver glucokinase (EC 2.7.1.2) has a key role in glucose metabolism. This enzyme is dependent on insulin for full activity. Failure of the pancreas to produce and secrete an adequate amount of insulin leads to Hyperglycemia and failure of glucose homeostasis. Current evidences indicate that vanadium compounds could mimic insulin action. Thus it appears that vanadyl sulfate may have an insulin-like effect on liver glucokinase activity. We investigated the effects of oral administration of vanadyl sulfate (0.5mg/ml in drinking water) on hepatic glucokinase activity in nondiabetic and diabetic rats. Male Wistar Methods: rats were randomly divided into four groups of control; vanadyl-treated control; streptozotocin(STZ)- injected; and vanadyl-treated STZ-injected. Animals were made diabetic by intraperitoneal (i.p) injection of STZ(60mg/Kg). Blood glucose level was measured by glucose oxidase-peroxidase method. Blood insulin was determined by the immunoradiometric assay (IRMA). Liver glucokinase activity was calculated from the difference between glucose phosphorylation capacity at 100 and 0.5mM glucose ,using the continuous assay. STZ-induced diabetic animals showed more than four fold increase in blood glucose levels and 83% decrease in blood insulin level. Vanadyl treatment (4 weeks) in diabetic rats lead to a significant decrease (P<0.001) in blood glucose levels, but vanadyl treatment did not significantly alter blood insulin levels in diabetic rats. Although in diabetic animals no significant activity of glucokinase was detected, but vanadyl treatment restored the enzyme activity to about 67.6% of the control value. Treatment of control rats with vanadyl sulfate did not significantly modify glucokinase activity and blood glucose levels, although in vanadyl-treated control group blood insulin level decreased by 58 %. Results obtained from the present study indicated that vanadyl sulfate mimic insulin action in vivo by reducing the high blood glucose level and restoring liver glucokinase activity in diabetic rat. So, one of the mechanism by which vanadyl sulfate restores normoglycemia is probably attributed to the hepatic effect of this compound.    

Neural crest cells migration and development toward developing trigeminal ganglia was investigated in rat during fetal development. In this study by using specific lectins, sialoglycoconjugated glycoproteins on the surface of neural crest cells was studied during this course of development. Lectins were included WGA (Triticium vulgaris specific for sialic acids), SBA (Glycin max specific for α-GalNac), MPA (Maclura pomifera specific for Galactose), PNA (Arachis hypogaea specific for Gal-GalNac) and GSA1B4 (Bandeiraea simplicifolia specific for Galactose), all of them conjugated to HRP. Sprague Dauley rats fetuses at different gestational ages were prepared for histological and histochemical procedures. Each section was treated with lectin and then DAB for recognition of glycoconjugates's terminal sugars. Migration of neural crest cells toward the ventrolateral of neural tube were observed with this histochemical tracing. Some of these migratory cells intensely reacted to WGA which is specific for sialic acids. A large aggregation of these cells were located beside the pons in higher gestational days and severely reacted with WGA These cells produced nerve fibers which were also severely reacted with WGA. These findings suggest that sialydated glycoconjugates are involved in development of trigeminal ganglia and formation of related nerve fibers distribution.        

Ionizing radiation has been shown to produce a broad variety of genetic alterations in humans and other species. Most genetic alterations are deletions. To study genetic alterations, assessment of somatic cell gene mutations induced by ionizing radiation is the proper method. In this study, intragenic and total gene deletions were analyzed in gamma ray induced 18HPRT mutants derived from T-lymphocytes PCR amplification of individual HPRT exons and multiplex PCR. HPRT mutants isolated by treatment of irradiated samples with 6-thioguanine.mPCR and PCR of individual exons of HPRT demonstrated that the intragenic and total gene deletions were not significantly different. In addition, the correlation between relative mutant cell numbers and different doses of gamma rays were determined. In this correlation, relative mutant number increased with great a slope in doses higher than 2 GY. Mapping of all intragenic deletion break points exhibited a nonrandom distribution of break points. The middle portion of HPRT gene was sensitive to gamma rays. The sensitivity was elevated by radiation dose. This study showed that the size of deletion appeared to be dependent on dose. Our results suggest that alteration in T-lymphocyte mutant numbers induced deletions, size of deletions and distribution of DNA break points appears to be dependent on radiation dose of low LET.    

In order to determine anti-tumor activities of two synthetic agents developed in the School of Pharmacy, MUMS, the potato disc assay was adopted and used in this study. Discs with specified diameter and height were cut out of potatoes and placed on plates containing agar 1.5%.A suspension of freshly grown Agrobacterium tumefactions strain B6 was inoculated on the discs, and the plates were incubated at 25°C for 30 days until crown gall tumors were appeared. After optimization of the conditions for growth and subsequent induction of crown gall tumor, vincrisrtine, a known anti-cancer drug was used to evaluate the assay. In the absence of vincristine tumors developed, while in the presence of enough concentration of the drug tumor production was inhibited. In a second step the tumor inhibitory effects of synthetic sulfonamide SSF and XSF were evaluated. Results of the test indicated anti-tumor activity for SSF and XSF compounds with the indication that XSF was more potent as an anti-tumor agent compared to its counterpart SSF.    

Muscle relaxant effect of Elaeagnus angustifolia L. (Elaeagnaceae) fruit seeds was studied in mice using the traction test. The aqueous and ethanolic extracts (i.p) induced a muscle relaxant effect in a dose dependent manner as effective as diazepam (1 mg/kg). The aqueous extract was partitioned with methanol-chloroform (MeCh)and n-butanol (Bu.) saturated with water. The MeCh and Bu. Fractions did not show activity. Preliminary phytochemical tests showed that the extract contains flavonoid. The results suggested that E. angustifolia fruit seeds exerted muscle relaxant activity via flavonoid component (s).      

The effects of genistein, an inhibitor of protein tyrosine kinase, and L-NAME (N-nitro-L-arginine methyl ester), an inhibitor of nitric oxide synthase, on endotoxin- induced shock were investigated in thiopental anesthetized rats. We also studied the effects of endotoxin on the vasconstrictor responses to sympathetic nerve stimulation (SNS) in the rat (10 mg kg-1, i.p.) produced by marked hypotension and a reduction of the pressor responses elicited by phenylephrine (0.1,0.3 and 3 g kg-1, i.v.). Pretreatment of rats with either genistein (10 mg kg-l i.p. 2h before endotoxin injection) or LNAME (0.1 mg kg-1, i.p.30 min before endotoxin injection) and a combination of both, attenuated the hypotension caused by endotoxin. Sympathetic nerve stimulation (SNS) caused a frequency-dependent vasoconstrictor response which was abolished by tetrodotoxin (10-7 M), prazoscin (10-7 M) and guanethidine (10-7 M). In mesenteric vascular beds removed from rats injected with endotoxin, the vasoconstrictor responses to SNS were markedly impaired. Although genistein and L-NAME preheatment attenuated the vascular hyporeactivity to phenylephrine, they did not modify the responses to SNS. These results indicate that genistein and L-NAME pretreatment prevent the hypotension and the delayed hyporeactivity to phenylephrine induced by endotoxin, but they failed to restore the vascular hyporeactivity to SNS.    

Zoonotic cutaneous leishmaniasis is a social health problem. There have been many researches such as leishmanization and use of non-pathogenic strain to control disease, but they have failed. We immunized 28 BALB/c mice by subcutaneous injection of 4x 105 live lizard leishmania promastigotes (a species of nonpathogenic leishmania promastigote). After 20 days, each mouse received a booster dose. After 30 days each were challenged by leishmania major promastigote. Macrophage - entranced promastigote was tested microscopically by macrophage peritoneal. aspiration. Mouse sample blood was given and cultured in NNN medium. We examined mouse visceral organs for leishmania amastigotes and did not observe leishmania amastigote in the experimental group, but they were observed in the control group. Only one of experimental mice exhibited leishmanial lesion, and all of the control mice had developed cutaneous leishmaniasis.