Microparticles Containing Curcumin Solid Dispersion: Stability, Bioavailability and Anti-Inflammatory Activity.

This work aimed at improving the solubility of curcumin by the preparation of spray-dried ternary solid dispersions containing Gelucire®50/13-Aerosil® and quantifying the resulting in vivo oral bioavailability and anti-inflammatory activity. The solid dispersion containing 40% of curcumin was characterised by calorimetry, infrared spectroscopy and X-ray powder diffraction. The solubility and dissolution rate of curcumin in aqueous HCl or phosphate buffer improved up to 3600- and 7.3-fold, respectively. Accelerated stability test demonstrated that the solid dispersion was stable for 9 months. The pharmacokinetic study showed a 5.5-fold increase in curcumin in rat blood plasma when compared to unprocessed curcumin. The solid dispersion also provided enhanced anti-inflammatory activity in rat paw oedema. Finally, the solid dispersion proposed here is a promising way to enhance curcumin bioavailability at an industrial pharmaceutical perspective, since its preparation applies the spray drying, which is an easy to scale up technique. The findings herein stimulate further in vivo evaluations and clinical tests as a cancer and Alzheimer chemoprevention agent.

Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report.

WHAT IS KNOWN AND OBJECTIVE:   Cannabis withdrawal in heavy users is commonly followed by increased anxiety, insomnia, loss of appetite, migraine, irritability, restlessness and other physical and psychological signs. Tolerance to cannabis and cannabis withdrawal symptoms are believed to be the result of the desensitization of CB1 receptors by THC. CASE SUMMARY:   This report describes the case of a 19-year-old woman with cannabis withdrawal syndrome treated with cannabidiol (CBD) for 10 days. Daily symptom assessments demonstrated the absence of significant withdrawal, anxiety and dissociative symptoms during the treatment. WHAT IS NEW AND CONCLUSION:   CBD can be effective for the treatment of cannabis withdrawal syndrome.

Influence of acetylator phenotype on the haematological and biochemical effects associated with dapsone in leprosy patients.

Methaemoglobinaemia and haemolytic anaemia were the principal side-effects observed in 30 leprosy patients undergoing long-term treatment with dapsone as a single drug or as part of multidrug therapy. Hepatic, pancreatic and renal evaluations showed no relevant clinical changes. Since N-acetylation is a major metabolic pathway for dapsone, slow acetylation phenotype may be a risk factor for the development of these reactions. To confirm this hypothesis we correlated acetylator phenotype and the haematological and biochemical effects induced by dapsone. No excess proportion of slow acetylators was found. We conclude that slow acetylators are not at greater risk of developing haematological side-effects of dapsone than fast acetylators.

A rapid, specific, and sensitive method for the determination of acetylation phenotype using dapsone.

An original, simple, specific, and rapid high-performance liquid chromatography assay for the determination of dapsone and monoacetyldapsone in human plasma is presented. The procedure consists of extracting the drugs and the internal standard (phenacetin) from 1 mL plasma with ethyl ether at alkaline pH. A liquid chromatograph equipped with a reversed-phase 5-microm C8 analytical column was used. The drugs were eluted with a mixture of water and methanol (70:30, v/v). Flow rate and wavelength were set at 1 mL/min and 286 nm, respectively. The precision, linearity, and limit of quantitation of the method were within acceptable limits. The method was considered adequate and has been used for the determination of the acetylator phenotype in population studies.

An improved method for the simultaneous determination of mandelic and phenylglyoxylic acids by gas chromatography.

We present a method that permits the simultaneous analysis of mandelic acid (MA) and phenylglyoxylic acid (PGA) in the urine of workers occupationally exposed to styrene. The method consists of urine extraction in acid medium with chloroform and the subsequent formation of the respective methyl esters. The samples were submitted to gas chromatography using a glass column packed with 10% SP-1000. Recoveries of 66.7% and 95.4% were obtained for MA and PGA, respectively, with limits of quantitation of 0.03 g/L for MA and 0.02 g/L for PGA. The method proved to be precise in terms of both intra-assay and interassay analysis, with coefficients of variation less than 10%.

Determination of clofazimine in leprosy patients by high-performance liquid chromatography.

An original, simple, specific, and rapid high-performance liquid chromatography assay for the determination of clofazimine in human plasma is presented. The procedure consists of extracting the drug and the internal standard (medazepam) from 0.5 mL plasma with dichloromethane/diisopropyl ether (1:1, v/v) at pH 3.0, after precipitating the proteins with methanol. The drugs were then quantitated on a reversed-phase C8 using a mobile phase consisting of a mixture of methanol/0.25 N sodium acetate buffer at pH 3.0 (74:26, v/v). The flow-rate and wavelength were set at 1 mL/min and 286 nm, respectively. The precision, linearity, and limit of quantitation of the method were within acceptable limits. The method was considered adequate and could be applied in studies involving blood level monitoring and pharmacokinetics in leprosy patients.

Determination of ametryn herbicide by bioassay and gas chromatography-mass spectrometry in analysis of residues in drinking water.

A simple, rapid and quantitative bioassay method was compared to a gas chromatography/mass spectrometry (GC/MS) procedure for the analysis of ametryn in surface and groundwater. This method was based on the activity of ametryn in inhibiting the growth of the primary root and shoot of germinating letuce, Lactuca sativa L. seed. The procedure was sensitive to 0.01 microgram/l and was applicable from this concentration up to 0.6 microgram/l. Initial surface sterilization of the seed, selection of pregerminated seed of certain root lengths and special equipment are not necessary. So, we concluded that the sensitivity of the bioassay method is compatible with the chromatographic method (GC-MS). However, the study of the correlation between methods suggests that the bioassay should be used only as a screening technique for the evaluation of ametryn residues in water.

Automated determination of rifampicin in plasma samples by in-tube solid-phase microextraction coupled with liquid chromatography.

A sensitive and automated method is described for determination of rifampicin in plasma samples for therapeutic drug monitoring by in-tube solid-phase microextraction coupled with liquid chromatography (in-tube SPME/LC). Important factors in the optimization of in-tube SPME are discussed, such as coating type, sample pH, sample draw/eject volume, number of draw/eject cycles, and draw/eject flow rate. Analyte pre-concentrated in the polyethylene glycol phase was directly transferred to the liquid chromatographic column by percolation of the mobile phase, without carryover. The method was linear over the 0.1-100 µg/mL range, with a linear coefficient value (r(2)) of 0.998. The inter-assay precision presented coefficient of variation ≤ 1.7%. The effectiveness and practicability of the proposed method are proven by analysis of plasma samples from ageing patients undergoing therapy with rifampicin.

Fructose-1,6-bisphosphate reduces inflammatory pain-like behaviour in mice: role of adenosine acting on A1 receptors.

BACKGROUND AND PURPOSE: D-Fructose-1,6-bisphosphate (FBP) is an intermediate in the glycolytic pathway, exerting pharmacological actions on inflammation by inhibiting cytokine production or interfering with adenosine production. Here, the possible antinociceptive effect of FBP and its mechanism of action in the carrageenin paw inflammation model in mice were addressed, focusing on the two mechanisms described above. EXPERIMENTAL APPROACH: Mechanical hyperalgesia (decrease in the nociceptive threshold) was evaluated by the electronic pressure-metre test; cytokine levels were measured by elisa and adenosine was determined by high performance liquid chromatography. KEY RESULTS: Pretreatment of mice with FBP reduced hyperalgesia induced by intraplantar injection of carrageenin (up to 54%), tumour necrosis factor alpha (40%), interleukin-1 beta (46%), CXCL1 (33%), prostaglandin E(2) (41%) or dopamine (55%). However, FBP treatment did not alter carrageenin-induced cytokine (tumour necrosis factor alpha and interleukin-1 beta) or chemokine (CXCL1) production. On the other hand, the antinociceptive effect of FBP was prevented by systemic and intraplantar treatment with an adenosine A(1) receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine), suggesting that the FBP effect is mediated by peripheral adenosine acting on A(1) receptors. Giving FBP to mice increased adenosine levels in plasma, and adenosine treatment of paw inflammation presented a similar antinociceptive mechanism to that of FBP. CONCLUSIONS AND IMPLICATIONS: In addition to anti-inflammatory action, FBP also presents an antinociceptive effect upon inflammatory hyperalgesia. Its mechanism of action seems dependent on adenosine production but not on modulation of hyperalgesic cytokine/chemokine production. In turn, adenosine acts peripherally on its A(1) receptor inhibiting hyperalgesia. FBP may have possible therapeutic applications in reducing inflammatory pain.

Simultaneous HPLC analysis of tricyclic antidepressants and metabolites in plasma samples.

A sensitive, selective and rapid reverse-phase high-performance liquid chromatographic method was developed for the simultaneous analysis of imipramine, desipramine, amitriptyline and nortriptyline in human plasma. The procedure consisted of extracting the drugs and the internal standard (clomipramine) from 1 ml plasma with hexane:isoamyl alcohol (99:1, v/v) in alkaline medium. A newly marketed column, LiChrospher 60 RP-select B (dp 5 microns) of Merck was employed. The mobile phase, consisting of acetonitrile/0.25 N sodium acetate buffer at pH 5.5 (50:50, v/v), was delivered at a flow rate of 1.0 ml/min, and detection at 254 nm. The precision, linearity and limit of quantification of the method were within acceptable limits. The method was considered adequate and has, therefore, been used in routine analysis for the therapeutic control of depressed patients.

A new derivatization procedure for the analysis of hippuric acid and m-methyl-hippuric acid by gas chromatography.

The industrial solvents, toluene and xylene, have physicochemical properties that can be hazardous to the workers exposed. Since hippuric acid and m-methyl-hippuric acid represent the products of toluene and xylene biotransformation in urine, they are used as biological markers in studies on occupational exposure to these solvents. Several methods have been used to determine hippuric acid and m-methyl-hippuric acid--either based on gas chromatography or on high-performance liquid chromatography. In this study we propose the derivatization of hippuric acid and methyl-hippuric acid using methanol in acid medium (HCl), a low-cost reagent with a low level of toxicity. The method has been routinely used in our laboratory for 1 year and has proven to be a reliable procedure for the biological control of occupational exposure to toluene and/or xylene.

Haematological and biochemical alterations in leprosy patients already treated with dapsone and MDT.

Dapsone (DDS) is useful in the treatment of a number of inflammatory conditions which are characterized by neutrophil infiltration. It is the drug of choice for the treatment of leprosy and prophylaxis of malaria. Haematological side effects of methaemoglobinaemia and haemolysis have been long recognized. However, the frequency and severity of these side effects in patients already treated with DDS as a single drug or as part of a multidrug therapy (MDT) have not been well documented. We report herein an investigation of the effect of dapsone long-term treatment on the haematological and biochemical alterations in leprosy patients undergoing dapsone as a single drug (DDS group) or as part of a multidrug therapy in combination with rifampin and clofazimine (MDT group). Methaemoglobinaemia and haemolytic anaemia were the principal side effects observed. Reticulocytes were found to be elevated (> 1.5%) in 90% of the patients. Heinz bodies were also detected (6.6% of the patients). The osmotic fragility test showed a reduction in cell resistance and in the evaluation of white cells a severe eosinophilia was found. Hepatic, pancreatic and renal evaluation by the determination of biochemical parameters showed rare and occasional changes of no apparent clinical significance. We conclude that haematological side effects of dapsone are significant even at doses currently used to treat leprosy (100 mg/day) and that rifampin and clofazimine do not increase the incidence of these effects during long-term treatment.