Uterine contraction induced by Tanzanian plants used to induce abortion.

Ethnopharmacological Relevance: Women in Tanzania use plants to induce abortion. It is not known whether the plants have an effect.

Aims Of Study: Collect data on plant use in relation to induced abortion and test the effect of plant extracts on uterine contraction.

Bioavailability of probucol from lipid and surfactant based formulations in minipigs: influence of droplet size and dietary state.

The influence of droplet size on the absorption from lipid and surfactant based formulations was evaluated from two self-emulsifying formulations, a surfactant solution, and an oil solution. The self-emulsifying formulations was a self-emulsifying (SEDDS) and a self-nanoemulsifying (SNEDDS) formulation containing equal lipid and surfactant load, but exhibiting a large difference (approx 100 times) in the mean particle diameter of the resultant emulsion. The formulations were evaluated in a bioavailability study in fasted and fed Göttingen minipigs using probucol as model drug.

Using biorelevant dissolution to obtain IVIVC of solid dosage forms containing a poorly-soluble model compound.

The usefulness of selected biorelevant dissolution media (BDM) to predict in vivo drug absorption was studied. Dissolution profiles of solid formulations of a poorly soluble model compound were compared in BDM simulating fasted and two levels of fed state. A non-physiologically relevant medium containing the cationic surfactant, cetrimide, was also investigated.

Carroll rearrangement to construct the norneolignan skeleton.

A three-step synthesis of the norneolignan skeleton involving the Carroll rearrangement as the key step has been developed and used for synthesis of the norneolignan skeleton, 1,3-diphenylpenta-1,4-diene and hinokiresinol.

The impact of an automated dose-dispensing scheme on user compliance, medication understanding, and medication stockpiles.

Background: It has been assumed that a new health technology, automated dose-dispensing (ADD), would result in benefits for medication users, including increased compliance, enhanced medication understanding, and improved safety. However, it was legislators and health professionals who pinpointed the assumed user benefits. Neither Danish nor international studies dealt with users' perspective on ADD in general or with respect to the pinpointed benefits, and thus exploration was needed.

Synergism in the repression of COX-2- and TNFalpha-induction in platelet activating factor-stressed human neural cells.

Platelet activating factor (PAF; beta-acetyl-gamma-O-hexadecyl-l-alpha-phosphatidylcholine) triggers a rapid pro-inflammatory gene expression program in primary cultures of human neural (HN) cells. Two genes and gene products consistently induced after PAF treatment are the cytosoluble prostaglandin synthase cycloooxygenase-2 (COX-2) and the pro-apoptotic tumor necrosis factor alpha (TNFalpha). Both of these mediators are associated with the activation of inflammatory signaling, neural cell dysfunction, apoptosis and brain cell death, and both have been found to be up-regulated after brain injury in vivo.

COX-1 and -2 activity of rose hip.

The objective of this study was to investigate whether the clinically observed efficacy of rose hip in the treatment of osteoarthritis is due to inhibition of cyclooxygenase-1 and -2. Water, methanol, dichloromethane and hexane extracts of rose hip were tested for in vitro COX-1 and 2 activity. The organic solvent extracts showed good inhibition of both COX-1 and 2.

Inflammation in Parkinson's disease: causative or epiphenomenal?

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a dramatic loss of dopaminergic neurons in the substantia nigra (SN). Several pathogenic mechanisms have been implicated in the demise of these cells, including dopamine-dependent oxidative stress, mitochondrial dysfunction, excitotoxicity, and proteasomal impairment. In recent years, the involvement of neuroinflammatory processes in nigral degeneration has gained increasing attention.

Effects of spinal cord stimulation on peripheral blood circulation in rats with streptozotocin-induced diabetes.

Objective.  The aim of this study was to investigate the effects of spinal cord stimulation (SCS) on peripheral circulation in rats with streptozotocin (STZ)-induced diabetes. Materials and Methods.

The polyacetylene falcarindiol with COX-1 activity isolated from Aegopodium podagraria L.

Extracts of Aegopodium podagraria L. were screened in vitro for cyclooxygenase-1 (COX-1) inhibitory activity. The isolation of the active compound falcarindiol was achieved by bioassay-guided fractionation.

Diflunisal salts of bupivacaine, lidocaine and morphine. Use of the common ion effect for prolonging the release of bupivacaine from mixed salt suspensions in an in vitro dialysis model.

The present work describes the characterization of diflunisal salts of the analgesic agents bupivacaine, lidocaine, and morphine including their solubility behaviour and release characteristics from solutions and selected salt suspensions in vitro using the rotating dialysis cell model. The solubility of the 1:1 salts at pH 7.4 differed by a factor of 9 with the bupivacaine and lidocaine salts representing the poorest and most soluble salt (0.

Structural development of self nano emulsifying drug delivery systems (SNEDDS) during in vitro lipid digestion monitored by small-angle X-ray scattering.

Purpose: To investigate the structural development of the colloid phases generated during lipolysis of a lipid-based formulation in an in vitro lipolysis model, which simulates digestion in the small intestine.

Materials And Methods: Small-Angle X-Ray scattering (SAXS) coupled with the in vitro lipolysis model which accurately reproduces the solubilizing environment in the gastrointestinal tract and simulates gastrointestinal lipid digestion through the use of bile and pancreatic extracts. The combined method was used to follow the intermediate digestion products of a self nano emulsified drug delivery system (SNEDDS) under fasted conditions.

The antinociceptive efficacy of buprenorphine administered through the drinking water of rats.

Postoperative pain management in laboratory animals is important for animal welfare and required under law in many countries. Frequent injection of analgesics to rodents after surgery is stressful for the animals and labour-intensive for animal care personnel. An alternative dosing scheme such as administration of analgesics in the drinking water would be desirable.

Novel 5-substituted 1-pyrazolol analogues of ibotenic acid: synthesis and pharmacology at glutamate receptors.

5-Substituted 1-pyrazolol analogues of ibotenic acid have been synthesized and pharmacologically characterized on ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs). The syntheses involved introduction of bromide, alkyls, phenyl and arylalkyls in the 5-position of 1-benzyloxypyrazole leading to 5-substituted (RS)-2-amino-(1-hydroxy-4-pyrazolyl)acetic acids (5a-l). The pharmacological activities of the synthesized analogues ranged from the 5-cyclopropylmethyl analogue (5f) with weak but selective affinity for NMDA receptors (IC(50)=35 microM), over the 5-n-propyl analogue (5c), which was a selective mGluR2 agonist (EC(50)=72 microM), to the 5-cyclohexylmethyl analogue (5g), which was a selective mGluR2 antagonist (K(i)=32 microM), and the 5-phenylethyl analogue (5j), which was a weak but apparently selective mGluR1 antagonist (K(i)=230 microM).

Synthesis and pharmacology of glutamate receptor ligands: new isothiazole analogues of ibotenic acid.

The naturally occurring heterocyclic amino acid ibotenic acid (Ibo) and the synthetic analogue thioibotenic acid (Thio-Ibo) possess interesting but dissimilar pharmacological activity at ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs). Therefore, a series of Thio-Ibo analogues was synthesized. The synthesis included introduction of substituents by Suzuki and Grignard reactions on 4-halogenated 3-benzyloxyisothiazolols, reduction of the obtained alcohols, followed by introduction of the amino acid moiety by use of 2-(N-tert-butoxycarbonylimino)malonic acid diethyl ester.

Studies on the metabolism of tolmetin to the chemically reactive acyl-coenzyme A thioester intermediate in rats.

Carboxylic acids may be metabolized to acyl glucuronides and acyl-coenzyme A thioesters (acyl-CoAs), which are reactive metabolites capable of reacting with proteins in vivo. In this study, the metabolic activation of tolmetin (Tol) to reactive metabolites and the subsequent formation of Tol-protein adducts in the liver were studied in rats. Two hours after dose administration (100 mg/kg i.

Study on the binding of Thioflavin T to beta-sheet-rich and non-beta-sheet cavities.

Amyloid fibril formation plays a role in more than 20 diseases including Alzheimer's disease. In vitro detection of these fibrils is often performed using Thioflavin T (ThT), though the ThT binding mode is largely unknown. In the present study, spectral properties of ThT in binding environments representing beta-sheet-rich and non-beta-sheet cavities were examined.

Characterization of prototype self-nanoemulsifying formulations of lipophilic compounds.

This study describes the evaluation and characterization of a self-nanoemulsifying drug delivery system (SNEDDS) consisting of a nonionic surfactant (Cremophor RH40), a mixture of long chain mono-, di-, and triacylglycerides (Maisine 35-1 and Sesame oil) and ethanol. Compositions containing 10% (w/w) ethanol, 40%-60% (w/w) lipid content, and 30%-50% (w/w) Cremophor RH40 were identified as pharmaceutically relevant, robust, and self-nanoemulsifying when dispersed in aqueous media. The influence of adding three different lipophilic model drug compounds (danazol, halofantrine, and probucol) to the SNEDDS was evaluated.

Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceans.

Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressant medications, primarily in the treatment of clinical depression. They are among the pharmaceuticals most often prescribed in the industrialized countries. Selective serotonin reuptake inhibitors are compounds with an identical mechanism of action in mammals (inhibit reuptake of serotonin), and they have been found in different aqueous as well as biological samples collected in the environment.

Structure, pharmacology and therapeutic prospects of family C G-protein coupled receptors.

Family C of G-protein coupled receptors (GPCRs) from humans is constituted by eight metabotropic glutamate (mGlu(1-8)) receptors, two heterodimeric gamma-aminobutyric acid(B) (GABA(B)) receptors, a calcium-sensing receptor (CaR), three taste (T1R) receptors, a promiscuous L-alpha-amino acid receptor (GPRC6A), and five orphan receptors. Aside from the orphan receptors, the family C GPCRs are characterised by a large amino-terminal domain, which bind the endogenous orthosteric agonists. Recently, a number of allosteric modulators binding to the seven transmembrane domains of the receptors have also been reported.

Human urine as test material in 1H NMR-based metabonomics: recommendations for sample preparation and storage.

Metabonomic approaches are believed to have the capability of revolutionizing diagnosis of diseases and assessment of patient conditions after medical interventions. In order to ensure comparability of metabonomic 1H NMR data from different studies, we suggest validated sample preparation guidelines for human urine based on a stability study that evaluates effects of storage time and temperature, freeze-drying, and the presence of preservatives. The results indicated that human urine samples should be stored at or below -25 degrees C, as no changes in the 1H NMR fingerprints have been observed during storage at this temperature for 26 weeks.

Identification of natural products using HPLC-SPE combined with CapNMR.

Two major development areas in HPLC-NMR hyphenation are postcolumn solid-phase extraction (HPLC-SPE-NMR) and capillary separations with NMR detection by means of solenoidal microcoils (CapNMR). These two techniques were combined off-line into HPLC-SPE-CapNMR, which combines the advantage of high loadability of normal-bore HPLC columns with high mass sensitivity of capillary NMR probes with an active volume of 1.5 microL.

CE frontal analysis based on simultaneous UV and contactless conductivity detection: a general setup for studying noncovalent interactions.

CE frontal analysis (CE-FA) has been established as a powerful tool to study noncovalent interactions between macromolecules and small molecules such as drug substances or pharmaceutical excipients. However, when using traditional commercial CE instrumentation, a serious drawback is related to the fact that only UV-active compounds can be studied. In recent years, contactless conductivity detection has become an attractive alternative to UV detection in CE due to its high versatility.

High resolution crystal structures of the p120 RasGAP SH3 domain.

X-ray structures of two crystal forms of the Src homology 3 domain (SH3) of the Ras GTPase activating protein (RasGAP) were determined at 1.5 and 1.8A resolution.