Mesenchymal stromal cells versus betamethasone can dampen disease activity in the collagen arthritis mouse model.

The objective of this study was to compare between the effects of mesenchymal stem cell (MSC) and betamethasone in the treatment of rheumatoid arthritis. Sixty male albino mice were divided equally into 2 models. They are MSC model, group 1: saline control group, group 2: collagen-induced arthritis (CIA), group 3: induced arthritis mice that received intravenous injection of MSCs. Betamethasone model, group 1: phosphate buffer saline, group 2: CIA, group 3: induced arthritis mice that received intraperitoneal injection of betamethasone. Mice arthritis models were assessed by clinical paw edema and X-rays, at the proper time of sacrefaction, tissues were collected and examined using real-time PCR, and synovial tissue was examined for interleukin-10, tumor necrosis factor α, cartilage oligomeric matrix protein and matrix metalloproteinase 3. While serum levels of rheumatoid factor and C-reactive protein were detected by enzyme-linked immunosorbent assay kits. Also blood erythrocyte sedimentation rate was detected. Histopathological, paw edema and PCR results showed improvement in the groups that received MSC compared with the diseased group and the groups which received betamethasone. MSC significantly enhanced the effect of collagen-induced arthritis treatment, which is superior to betamethasone treatment, likely through the modulation of the expression of various cytokines.

Counteraction of nifedipine-induced hyperglycaemia by metformin.

Nifedipine-induced hyperglycaemia in rats was counteracted by concurrent administration of metformin (500 mg/kg p.o.). However, glibenclamide (5 mg/kg p.o.) did not change the hyperglycaemic effect of nifedipine. It is suggested that nifedipine-induced hyperglycaemia was not related to pancreatic effect and might be attributed to extra pancreatic mechanism by preventing the action of insulin in the tissues. Therefore, counteraction of nifedipine-induced hyperglycaemia by metformin, may play a role in diabetic patients treated with nifedipine.

Interaction between diazepam and oral antidiabetic agents on serum glucose, insulin and chromium levels in rats.

This study was undertaken to investigate the effect of diazepam in the presence and absence of glibenclamide, metformin or their combination on serum levels of glucose, insulin and chromium in rats. Results indicated that diazepam (10 mg/kg i.p.) induced marked hyperglycaemic effects in hyperglycaemic rats. This effect was associated with significant reductions in serum chromium levels and insignificant reduction in serum insulin levels. Diazepam-induced hyperglycaemia was counteracted by concurrent administration of glibenclamide (5 mg/kg orally), metformin (500 mg/kg orally) or their combination. The effect of diazepam on serum chromium level was counteracted partially by administration of glibenclamide and augmented in the presence of metformin or its combination with glibenclamide. It is concluded that the diazepam-induced hyperglycaemia, as well as the hypoglycaemic effect of glibenclamide, might be related to changes in serum chromium levels.

Effect of bromocriptine on lipid plasma levels in rats.

Results show that bromocriptine induced marked alterations in plasma levels of cholesterol and lipids in response to acute and chronic administrations in rats. Two hours after an I.P. dose of 10 mg/kg, bromocriptine mesylate caused significant reductions in plasma levels of total high density lipoprotein (HDL) and high density lipoprotein cholesterol (HDL cholesterol). At a dose of 20 mg/kg, bromocriptine mesylate induced significant elevations in plasma levels of total cholesterol, total HDL, HDL cholesterol, total low density lipoproteins (LDL), and low density lipoprotein cholesterol (LDL cholesterol). Injected at a dose of 4 or 10 mg/kg daily for 14 consecutive days, bromocriptine mesylate caused significant increases in plasma levels of total cholesterol, LDL cholesterol and total LDL whereas the levels of HDL cholesterol, total HDL triglycerides (TG) were reduced. At a dose of 20 mg/kg all parameters were significantly increased. Marked hyperglycaemia was noticed in response to doses of 10, 15 and 20 mg/kg injected daily for 14 consecutive days or 2 hrs after a single administration of 15 mg/kg. Plasma insulin activity was reduced 2 hours after injection of bromocriptine at a dose of 15 mg/kg Likewise, a significant reduction in plasma insulin activity was observed in response to daily I.P. injections of bromocriptine at a dose of 15 mg/kg. Hyperglycaemic and hypoinsulinaemic effects of bromocriptine (acute and chronic) were markedly decreased when sulpiride, a dopaminergic D2 antagonist, was injected at an I.P. dose of 10 mg/kg before bromocriptine. Plasma ACTH activity was significantly increased in response to bromocriptine (15 mg/kg I.P.) in acute and chronic experiments. This effect was markedly diminished when sulpiride was injected prior to bromocriptine. In conclusion, bromocriptine induced marked elevations in plasma levels of total cholesterol and lipids which are likely to be related to hyperglycaemic and hypoinsulinaemic effects.

Mechanism of bromocriptine-induced hyperglycaemia.

Results reveal that bromocriptine at a dose of 6 mg/kg. I.P. in mice caused a significant hyperglycaemic effect which was accompanied by a marked increase in liver glycogen. After adrenalectomy, the effect of bromocriptine on serum glucose level was reduced whereas its effect on liver glycogen content was abolished. In rats, administration of bromocriptine (17.5 mg/kg I.P.) induced a significant rise in serum glucose level which was associated with marked reduction in serum insulin activity and increase in serum corticosterone level with no effect on serum triiodothyronine (T3) or thyroxine (T4) levels. It could be concluded that bromocriptine-induced hyperglycaemia might be attributed at least partially to inhibition of insulin release and stimulation of corticosterone secretion.

Effects of alpha-adrenoceptor agonists and antagonists on insulin secretion, calcium uptake, and rubidium efflux in mouse pancreatic islets.

Epinephrine, norepinephrine or the more selective alpha-2 adrenoceptor agonist, clonidine, inhibited insulin release from isolated pancreatic islets of lean mice or obese mice homozygous for the gene ob. Clonidine was highly effective at 0.1 mumol/l. In contrast, the preferential alpha-1 adrenoceptor agonist, phenylephrine, had no or only a modest effect at 10 mumol/l. The effects of norepinephrine or clonidine were counteracted by yohimbine, a preferential blocker of alpha-2 receptors, but not by prazosine, an alpha-1 receptor blocker. The glucose-stimulated uptake of 45Ca2+ in the islets was only consistently inhibited by epinephrine. This effect was counteracted by yohimbine. Clonidine had no effect on the release of 86Rb+ from preloaded islets. It is concluded that insulin secretion is suppressed by alpha-2 receptor agonism in the pancreatic beta-cells and that this effect is mediated by mechanisms other than the transmembrane fluxes of calcium or potassium ions.

Effects of tetracycline and diazepam on insulin secretion and adenylyl cyclase activity of isolated rat islets of Langerhans.

Tetracycline (2 and 20 micronM) inhibited glucose-stimulated insulin secretion from isolated rat islets of Langerhans, although it failed to alter tolbutamide-stimulated insulin release. Diazepam (10 micronM) potentiated tolbutamide-stimulated insulin release and at a concentration of 1 mM increased glucose-stimulated insulin release. Tetracycline (20 and 200 micronM) or diazepam (10, 100 and 1,000 micronM) inhibited adenylyl cyclase activity of islets homogenate. These results suggest that the effect of tetracycline on insulin secretion might be in part due to inhibition of adenylyl cyclase of the islets. However, the effect of diazepam on insulin secretion is not mediated through the adenylyl cyclase system.