Effect of intradermal injection of heparinase III on skin wound healing in diabetic rats.

AIM: neuropathy and vascular damage in this disease. Heparanase is an endoglycosidase that degrades heparan sulfate in the extracellular matrix and is believed to promote angiogenesis. The present study has been performed to investigate the effect of heparinase III (an enzyme which exclusively cleaves heparan sulfate) on wound healing in diabetic rats. METHODS: The rats became diabetic by a single streptozotocin injection. Two weeks later, a wound was created by excision of the skin in the left paravertebral area. Heparinase III (0.2 unit) was injected intradermally around the wound every 5 days, starting on day one, for a total of three doses. The wound area was measured every 3 days. After completion of wound healing, full thickness skin samples were taken from the wound sites and evaluated for volume density of the collagen bundles, numerical density of the fibroblasts, and length density of the vessels. RESULTS: Heparinase III accelerated wound closure compared to control diabetic animals. Microscopical examination revealed that it increased angiogenesis with no significant effect on collagen density and the number of fibroblasts. CONCLUSION: Heparinase III induces angiogenesis and improves wound healing in diabetic animal model.

Study of antibiotic prescribing among dental practitioners in Shiraz, Islamic Republic of Iran.

Inappropriate prescribing of antibiotics by health care professionals is a worldwide concern. This study evaluated the knowledge and practices of dental practitioners in the city of Shiraz, Islamic Republic of Iran regarding their therapeutic use of antibiotics for patients with dentoalveolar infections. Of 219 (48.6%) dentists responding to the questionnaire more than 40% would prescribe antibiotics for localized fluctuant swelling and for problems for which antibiotics are not required according to good practice guidelines (acute pulpitis, chronic apical infection, periodontal abscess, chronic gingivitis, chronic periodontitis, pericoronitis and dry socket). A majority correctly prescribed antibiotics for acute periapical infection (77.2%), cellulitis (75.3%) and acute ulcerated gingivitis (63.0%). Amoxicillin was the most frequently prescribed antibiotic for all clinical conditions but there was a wide variation in dosage, frequency and duration for all antibiotics used. Guidelines on rational antibiotic use are needed for dental practitioners in the Islamic Republic of Iran.

Study of antibiotic prescribing among dental practitioners in Shiraz, Islamic Republic of Iran

Inappropriate prescribing of antibiotics by health care professionals is a worldwide concern. This study evaluated the knowledge and practices of dental practitioners in the city of Shiraz, Islamic Republic of Iran regarding their therapeutic use of antibiotics for patients with dentoalveolar infections. Of 219 [48.6%] dentists responding to the questionnaire more than 40% would prescribe antibiotics for localized fluctuant swelling and for problems for which antibiotics are not required according to good practice guidelines [acute pulpitis, chronic apical infection, periodontal abscess, chronic gingivitis, chronic periodontitis, pericoronitis and dry socket]. A majority correctly prescribed antibiotics for acute periapical infection [77.2%], cellulitis [75.3%] and acute ulcerated gingivitis [63.0%]. Amoxicillin was the most frequently prescribed antibiotic for all clinical conditions but there was a wide variation in dosage, frequency and duration for all antibiotics used. Guidelines on rational antibiotic use are needed for dental practitioners in the Islamic Republic of Iran

Effects of mebudipine and dibudipine, two new calcium-channel blockers, on rat left atrium, rat blood pressure and human internal mammary artery.

Mebudipine and dibudipine are two new dihydropyridine calcium-channel blockers that have been synthesized in our laboratory. In a previous study, they showed considerable relaxant effect on vascular and ileal smooth muscle. Here, the pharmacological effects of mebudipine and dibudipine on isolated rat left atrium, rat blood pressure and isolated human internal mammary artery are described. Results are compared with those obtained for nifedipine. Mebudipine and dibudipine reduced contraction force of rat left atrium (pIC30 values: 5.37+/-0.13 and 5.49+/-0.15, respectively) but their negative inotropic effects were significantly weaker than that of nifedipine (pIC30 value: 6.63+/-0.11). Mebudipine and dibudipine lowered rat blood pressure. The hypotensive effect of mebudipine was similar to that of nifedipine while dibudipine was weaker than nifedipine. It was found that the half-life of the hypotensive action of dibudipine (41.91+/-3.77 min, 31.13+/-2.26 min and 28.20+/-4.37 min at 2, 4 and 8 mg kg(-1) orally administered doses, respectively) was longer than that of nifedipine (11.85+/-2.88 min, 16.65+/-2.42 min and 14.03+/-0.10 min at the same doses, respectively). Also, it appeared that mebudipine had a slower rate of absorption compared with nifedipine (the time to reach peak hypotensive action at 2, 4 and 8 mg kg(-1) orally administered doses were, respectively, 24.00+/-6.96 min, 23.75+/-2.39 min and 15.00+/-2.04 min for mebudipine and 7.80+/-0.86 min, 13.75+/-3.15 min and 833+/-0.88 min for nifedipine). The two new compounds, as well as nifedipine, relaxed KCl-treated isolated human internal mammary artery (pEC50 values; 7.87+/-0.12, 7.22+/-0.24 and 7.67+/-0.12 for mebudipine, dibudipine and nifedipine, respectively). The relaxant effects of mebudipine and dibudipine did not show any significant difference compared with that of nifedipine. It is concluded that these new compounds are weak cardiodepressants and, with due attention to its significant vasorelaxant action, mebudipine is a vasoselective compound. In addition, these two compounds have potent blood pressure lowering effects. Also, their vasorelaxant action can be reproduced in human vascular preparations.

Effect of diazoxide, an ATP-dependent potassium-channel opener, on isolated aortae of normal and diabetic rats.

1. The effect of diazoxide on the potassium-induced contraction and its inhibitory effect on noradrenaline-induced contraction were studied in the isolated aortic rings of normal and streptozocin-treated diabetic rats. 2. Diazoxide relaxed potassium-induced contraction in normal and diabetic rat aortae. There was no statistically significant difference in the relaxing effect of diazoxide in these two groups of rats. Glibenclamide inhibited the relaxing effect of diazoxide in normal and diabetic rat aortae to the same extent. Pretreatment of tissues with diazoxide prevented the noradrenaline-induced contraction. This inhibitory effect significantly differed between normal and diabetic rats. 3. It is concluded that, in the rat aorta, the state of potassium channels and the potency of diazoxide to open these channels are not affected by experimental diabetes. The observed differences between the responses of normal and diabetic aortae to the inhibitory effect of diazoxide on noradrenaline-induced contraction can be attributed to a mechanism(s) other than potassium-channel opening by diazoxide, which might be modified in diabetes, or to different consequences after potassium-channel opening in diabetic tissues compared with normal tissues.

Synthesis and biological activity of two new calcium-channel blockers, mebudipine and dibudipine.

Dihydropyridine derivative calcium-channel blockers are widely used in the therapy of hypertension, angina pectoris and other cardiovascular diseases. Because the prototype of dihydropyridine derivatives, nifedipine, does not have the optimum pharmacokinetic and pharmacodynamic characteristics, attempts have been made to synthesize other drugs in this class with improved properties. The synthesis and biological activity of two new calcium-channel blockers, non-symmetrical (mebudipine) and symmetrical (dibudipine) analogues of nifedipine, is described herein. The pharmacological potencies of the compounds were evaluated by studying their effects on the contractions of isolated guinea-pig ileum and rat aortic rings. Results were compared with those obtained from nifedipine. The new analogues and nifedipine inhibited the contractile response of guinea-pig ileum to electrical stimulation and the pIC50 value of the compounds did not differ significantly from each other. The compounds also antagonized the contractile responses of K+-depolarized guinea-pig ileum to cumulative concentrations of calcium. The inhibitory effect of mebudipine was significantly higher than that of nifedipine whereas the inhibitory effects of dibudipine and nifedipine were not different. All three compounds relaxed KCl (40 mM)-treated isolated aortic rings; the pIC50 values for relaxation were: mebudipine > nifedipine > dibudipine. It is concluded that these new dihydropyridine derivatives are potent relaxants of vascular and ileal smooth muscles and therefore have high potential for use as antihypertensive and anti-anginal agents.