Comparison of the effect of levodopa and bromocriptine on naloxone-precipitated morphine withdrawal symptoms in mice

In this study, the effect of l-dopa and bromocriptine on morphine withdrawal syndrome was compared. Both l-dopa (125, 250 mg/kg, i.p.) and low doses of bromocriptine (0.04, 0.08 mg/kg, i.p.) potentiated naloxone-induced morphine withdrawal symptoms such as jumping, climbing and rearing in mice. Higher doses of bromocriptine (0.16, 0.32 mg/kg, i.p.) attenuated these naloxone-induced symptoms. SKF 83566, D(1) dopamine antagonist (0.4, 0.8 mg/kg, i.p.) and sulpiride, D(2) dopamine antagonist (5, 10 mg/kg, i.p.) when used alone, also produced inhibitory effects on naloxone-induced morphine withdrawal symptoms. Pretreatment with sulpiride (5, 10 mg/kg, i.p.) and SKF 83566 (0.4, 0.8 mg/kg, i.p.) attenuated the potentiating effects of l-dopa on withdrawal symptoms significantly. Pretreatment with sulpiride also decreased the potentiating effect of bromocriptine and reinforced the inhibitory action of it, but SKF 83566 pretreatment just reinforced the effect of higher doses of bromocriptine. Concurrent pretreatment of animals with sulpiride (10 mg/kg, i.p.) and SKF 83566 (0.8 mg/kg, i.p.) markedly decreased the potentiating effects of l-dopa and bromocriptine and reinforced the inhibitory action of bromocriptine on the naloxone-induced morphine withdrawal syndrome. Prazosin, alpha(1) antagonist (1, 2 mg/kg, i.p.) decreased the naloxone-induced morphine withdrawal syndrome significantly. Pretreatment with yohimbine, alpha(2)-antagonist (5 mg/kg, i.p.) reversed the inhibitory effects of bromocriptine (0.16, 0.32 mg/kg, i.p.) on naloxone-induced morphine withdrawal syndrome significantly. In conclusion, our results show that bromocriptine at lower doses (0.04, 0.08 mg/kg, i.p.) acts similar to l-dopa, but at higher doses (0.16, 0.32 mg/kg, i.p.) shows different effects on naloxone-induced morphine withdrawal syndrome which may be due to the interaction of bromocriptine with alpha-adrenoceptors. Copyright 2000 John Wiley & Sons, Ltd.     

Temporary dermal scatter reduction: quantitative assessment and implications for improved laser tattoo removal

BACKGROUND AND OBJECTIVES: Temporary dermal clearing, i.e., reduction in the attenuation coefficient of the dermis and epidermis, may lead to improved laser tattoo removal by providing increased efficiency of laser delivery to embedded ink particles and enabling the use of shorter wavelength visible lasers more effective on certain inks. STUDY DESIGNS/MATERIALS AND METHODS: In a hairless guinea pig model of human tattoo, we tested both intradermal and transdermal application of glycerol, using visual inspection, spectral analysis, and optical coherence tomography techniques to assess effectiveness. In controlled experiments, we compared the outcomes of single laser treatment sessions for both cleared and uncleared tattoo sites using Q-switched 755 and 532 nm lasers on three different inks. RESULTS: Intradermal injection of clearing agents induced dermal clearing but resulted in necrosis and scar. Transdermal application of clearing agents resulted in moderate reversible clearing, which was localized to the superficial layers of the skin and did not result in complications. Statistically significant differences in laser treatment outcome were observed relative to a number of treatment parameters including the treatment of certain tattoos by short wavelength lasers. CONCLUSIONS: Temporary clearing of superficial skin layers may be performed in an apparently safe and reliable manner. Clearing should lead to increased penetration of laser light to tattoos and should, therefore, increase treatment efficiency. Further study is needed to determine the degree to which this change is of clinical value.     

Development and evaluation of buccoadhesive propranolol hydrochloride tablet formulations: effect of fillers

The buccal mucosa has been investigated for local and systemic delivery of therapeutic peptides and other drugs that are subjected to first-pass metabolism or are unstable within the rest of the gastrointestinal tract. Propranolol hydrochloride (propranolol HCl) is subjected to first-pass effect, therefore formulation of buccal-adhesive dosage form can circumvent this effect. The effect of lactose (a soluble excipient) and dicalcium phosphate (DCP) (an insoluble excipient) on dissolution rate, kinetic of release and adhesion force of buccal-adhesive tablets of propranolol HCl were evaluated. Each tablet composed of 80 mg propranolol HCl, 80 mg hydroxypropylmethylcellulose (HPMC) K4M, polycarbophil AA1 and lactose or DCP with different ratios. The results showed that the presence of the fillers increased dissolution rate of the drug. The release data also showed that the effect of lactose on the dissolution rate was greater than the DCP. Kinetic release of propranolol HCl from buccal-adhesive matrices was affected by the different ratios of polymers and fillers. The fillers reduced the bioadhesion force and this effect was more considerable in formulation containing DCP. In order to determine the mode of release, the data were analyzed based on the equation Q =kt(n). The results showed that an increase in the concentration of HPMC K4M resulted in a reduction in the value of n. The value of n was not significantly affected by an increase in the concentration of lactose or DCP. The values of n in this study were calculated to be between 0.461 and 0.619, indicating both diffusional release and erosional mechanism.     

Pharmacokinetics of mebudipine, a new calcium antagonist, following single intravenous and oral administrations in rats

The pharmacokinetics of a new calcium antagonist, mebudipine, was studied after a single intravenous (0.5 mg/kg) and oral (10 mg/kg) administration to rats. After intravenous dosing, the plasma concentration of mebudipine declined biexponentially with a terminal half-life of 2.84 h. The blood clearance was 1.67 l/h/kg and the volume of distribution at steady state was found to be 6.26 l/kg. After oral dosing (10 mg/kg), the C(max) of mebudipine was 25.9+/-9.79 ng/ml. The oral bioavailability was low (< 2%) suggesting a marked first-pass effect. The distribution of mebudipine into some tissues such as brain, heart, liver and kidney following intravenous administration (0.5 mg/kg) was studied and a rapid distribution of mebudipine into these tissues was found. It was concluded that brain, heart, liver and kidney are in the same compartment as plasma (central).     

The role of adaptor protein Ste50-dependent regulation of the MAPKKK Ste11 in multiple signalling pathways of yeast

In Saccharomyces cerevisiae, Ste50 functions in cell signalling between the activated G protein and the mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) Ste11. ScSte50 is an essential component of three MAPK-mediated signalling pathways, which control the mating response, invasive/filamentous growth and osmotolerance (HOG pathway), respectively. ScSte50 signalling may also contribute to cell wall integrity in vegetative cells. The protein contains a sterile alpha motif (SAM) and a putative Ras-associated domain (RAD), which are essential for signal transduction. Ste50 and Ste11 interact constitutively via their SAM regions. Ste50 interacts weakly and probably transiently with the pheromone receptor-bound heterotrimeric G protein G(alpha beta gamma), and with the small G proteins Cdc42, Ras1 and Ras2. It is specifically the RAD region of Ste50 that mediates the interactions with Cdc42 and Ras. Homologues of ScSTE50 are also found in other fungi, like S. kluyveri, Hansenula polymorpha, Candida albicans and Neurospora crassa. In this review, the role of Ste50 as an adaptor that links the G protein-associated Cdc42-Ste20 kinase complex to the effector kinase Ste11 and thus modulates signal transduction, especially in the pheromone-response pathway of S. cerevisiae, is discussed.     

A method for fabricating a cast post and core that is esthetic when used under an all-ceramic crown

This article presents a technique to enhance the optic qualities of all-ceramic crowns when placed over a cast post and core. An opaque layer is necessary over a metal structure, such as a cast core, to reduce light absorption and increase the reflectance of the metal. The desired effect is to raise the value of the core in order to approach the optic qualities of dentin. However, the problem of reflectance is fully eliminated by the use of an opaque layer of ceramic. The translucence of a ceramic crown may not be limited by the use of opaque material under the crown. This procedure requires the placement of an opaque layer of ceramic on the core, thereby moving such a layer 0.3 to 0.5 mm more deeply from the surface of the restoration. This allows more depth and translucence to the crown, as light penetrates further into the crown.