Micronization and microencapsulation of felodipine by supercritical carbon dioxide

Felodipine (FLD) is a poorly water-soluble drug. To improve its dissolution rate, the rapid expansion of supercritical solutions (RESS) technique was used to prepare micronized FLD drug particles, which were encapsulated in poly-(ethylene glycol) 4000 (PEG 4000). The physical properties of the encapsulated drug particles were characterized by a variety of analytical methods, including optical light microscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (powder-XRD) and the dissolution behaviour of FLD was studied in the microparticles. The supercritical condition of micronized FLD occurred at a relatively high pressure and moderate temperature. FLD–PEG 4000 microparticles compared well with micronized FLD. RESS was effective in reducing the particle size of FLD; spot-shaped micronized FLD and popcorn-shaped FLD–PEG 4000 microparticles were observed. The particulate properties of the microparticles included a narrow distribution and uniform size. Thermodynamic analysis showed an implantation interaction between FLD and PEG 4000 molecules, but no polymorphism in the micronized FLD or FLD–PEG 4000 microparticles. FLD–PEG 4000 microparticles had a significantly faster drug dissolution rate than micronized FLD. These data show that RESS can be used to prepare FLD–PEG 4000 microparticles with small particle size (2–6?µm) and enhanced dissolution rate.     

In vitro hypoglycemic effects of hot water extract from Auricularia polytricha (wood ear mushroom)

Viscous dietary fibers were shown to alleviate postprandial blood glucose. Auricularia polytricha (wood ear mushroom, WEM) contains rich amount fibers and water extract WEM was highly viscous. This study aimed to investigate whether WEM extract exhibited hypoglycemic effect in vitro. The effects of WEM extract on glucose adsorption, glucose diffusion, starch digestion and α-amylase activity were examined and compared to those of two high soluble fibers, psyllium and oat fiber and one insoluble fiber, cellulose. Our results showed that WEM extract and psyllium possessed similar ability to adsorb glucose which may thus decrease the level of dialysis glucose. The decrease of dialysis rate is dose-dependent. WEM extract can also suppress the activity of α-amylase which may thus inhibit the digestion of polysaccharides. Since WEM extract exhibited the ability to adsorb glucose and to suppress the activity of α-amylase; it might contribute a beneficial effect on postprandial levels of blood sugar.     

Preparation of inhalable salbutamol sulphate using reactive high gravity controlled precipitation

Reactive high gravity controlled precipitation (HGCP) was carried out to produce salbutamol sulphate (SS) particles suitable for inhalation. Aqueous solutions of free salbutamol base and sulphuric acid were mixed intensely inside a HGCP reactor to form the particles. Spray drying was employed to obtain dry powders. Physical properties of the powders were characterised by scanning electron microscopy, X-ray powder diffraction, thermal gravimetric analysis and dynamic water vapour sorption. Aerosol performance of the powders was measured using an Aeroliser connected to a multiple stage liquid impinger operating at 60 L/min. The results showed that the reactive HGCP powder, comprising primary SS sub-micron particles (approximately 100 nm in width and approximately 500 nm in length) packed into loose spherical agglomerates of about 2 microm in diameter, is of the same polymorphic form as the raw crystalline material, has a high specific surface area (24.7 +/- 0.1 m(2)/g), but a low moisture content (0.2%) and low moisture uptake (1.4% at RH 90%). The aerosol performance of the reactive HGCP powder is excellent, showing FPF(loaded) and FPF(emitted) of 76 +/- 5% and 83 +/- 7%, respectively, with low capsule and device retention. In conclusion, reactive HGCP followed by spray drying is suitable to produce stable crystalline powders of salbutamol with enhanced inhalation properties.     

Quantitative study of [(pF)Phe4,Arg14,Lys15]nociceptin/orphanin FQ-NH2 (UFP-102) at NOP receptors in rat periaqueductal gray slices

The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is a novel member of the opioid receptor family with little affinity for traditional opioids. This receptor and its endogenous ligand, N/OFQ, are widely distributed in the brain and are implicated in many physiological functions including pain regulation. [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-102) is a newly developed peptide agonist of NOP receptors. In this study, we quantitatively investigated the effect of UFP-102 at native NOP receptors of the ventrolateral periaqueductal gray (PAG), a crucial midbrain area involved in pain regulation and enriched with NOP receptors, using blind patch-clamp whole-cell recording technique in rat brain slices. UFP-102, like N/OFQ, induced an outward current in ventrolateral PAG neurons and increased the membrane current elicited by a hyperpolarization ramp from -60 to -140 mV. The current induced by UFP-102 was characterized with inward rectification and had a reversal potential near the equilibrium potential of K(+) ions, indicating that UFP-102 activates G-protein coupled inwardly rectifying K(+) channels. The effect of UFP-102 was concentration-dependent with the maximal effect similar to that of N/OFQ. The EC(50) value was 11+/-2 nM, which is 5 fold lower than that of N/OFQ. The effect of UFP-102 was not affected by naloxone while competitively antagonized by UFP-101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2)), a potent NOP receptor antagonist, with a pA(2) value of 6.7. These results suggest that UFP-102 is a full agonist at the postsynaptic NOP receptors of the midbrain of rats and is 5 fold more potent than N/OFQ.     

Phase II study of oxaliplatin in combination with continuous infusion of 5-fluorouracil/leucovorin as first-line chemotherapy in patients with advanced gastric cancer

This study was designed to determine the efficacy and safety of biweekly oxaliplatin in combination with infusional 5-fluouracil (5-FU) and leucovorin in patients with advanced gastric cancer (AGC). Fifty-five eligible patients with measurable or assessable M/AGC (median age 62 and 90% of patients presented with metastasis) received oxaliplatin (85 mg/m2) intravenous infusion for 2 h, followed by intravenous infusion of 5-FU (3000 mg/m2) and leucovorin (100 mg/m2) for 46 h every 14 days until the patient's disease was either in progression, unacceptable toxicity, patient's withdrawal or the investigators' decision to discontinue treatment. Of the 55 enrolled patients, 48 were evaluable for response. Three patients (5.4%) showed complete remission and 20 patients (36.4%) achieved partial response. The overall response rate was 47.9%. Nineteen patients (34.5%) had stable disease and six patients (10.9%) showed progressive disease. The median time to progression was 5.6 months and the median overall survival was 10.8 months. Grade 3/4 toxicities included leucopenia (12.7%), thrombocytopenia (5.4%), diarrhoea (3.6%) and vomiting (9.1%). Peripheral neuropathy was noted in 61.8% of the patients (grade 1/2: 54.5%; grade 3: 7.3%). Our study confirmed that the combination of oxaliplatin and continuous infusion of 5-FU/leucoverin without bolus 5-FU as first-line chemotherapy is active for patients with AGC and relatively safe with lower haematological toxicity.     

Effects of hesperidin on cyclic strain-induced endothelin-1 release in human umbilical vein endothelial cells

1. Hesperidin, a member of the flavanone group of flavonoids, can be isolated in large amounts from the rinds of some citrus species and has been reported to have antihypotensive and vasodilator properties. However, the mechanism of action of hesperidin in the prevention and treatment of vascular diseases remains unclear. 2. The vascular endothelium can produce potent contracting factors, such as endothelin (ET)-1, and endothelium-derived relaxing factors, such as nitric oxide (NO). The aims of the present study were to test the hypothesis that hesperidin may alter strain-induced ET-1 secretion and NO production and to identify the putative underlying signalling pathways in human umbilical vein endothelial cells (HUVEC). 3. Hesperidin (10 and 100 micromol/L) inhibited strain-induced ET-1 secretion. Hesperidin also inhibited strain-induced increases in the formation of reactive oxygen species and extracellular signal-regulated kinase (ERK) phosphorylation. 4. Hesperidin treatment of HUVEC enhanced NO production, endothelial NO synthase (eNOS) activity and the phosphorylation of eNOS and Akt. Furthermore, hesperidin modulated strain-induced ET-1 release and suppressed ERK phosphorylation in part via the NO/protein kinase G pathway. 5. In summary, we have demonstrated that hesperidin inhibits strain-induced ET-1 secretion and enhances NO production in HUVEC.     

A novel NO-production-inhibiting triterpene and cytotoxicity of known alkaloids from Euonymus laxiflorus

A new triterpene, laxifolone A (1), four known sesquiterpene alkaloids, ebenifoline E-II (2), carigorinine E (3), euojaponine C (4), and emarginatine E (5), and six triterpenoids, 3-hydroxyolean-12-en-22,29-gamma-lactone, 3,11-dioxo-beta-amyrene, 3beta,22alpha-dihydroxyolean-12-en-29-oic acid, 28,29-dihydroxyfriedelan-3-one, 29-hydroxy-3-oxo-D:A-friedooleanan-28-oic acid, and putranjivadione, were isolated from the stems and leaves of Euonymus laxiflorus. Structural elucidations of these compounds were established by spectral analysis. Compound 1 displayed significant nitric oxide (NO) inhibitory effect.     

Relationships between medical beliefs of superiority of Chinese or Western medicine, medical behaviours and glycaemic control in diabetic outpatients in Taiwan

A considerable proportion of Taiwanese people believe that Chinese medicine is superior for treating the cause of disease (curative therapy) whereas western medicine is mostly concerned with treating symptoms (symptomatic therapy). As a result, when illness arises, the combined use of both Chinese and western medicine is a common practice and referred to as pluralistic health-seeking behaviour. The purpose of this cross-sectional study was to explore the relationship between beliefs of superiority of western or Chinese medicine, utilisation of therapy and glycaemic control in patients with diabetes from outpatient departments. The study was conducted between 20 December 2005 and 20 January 2006. We approached 176 patients consecutively, and 151 (85.8%) completed the survey. Seventy-nine patients with diabetes from a municipal Chinese medicine hospital and 72 patients from a near by western medicine hospital in southern Taiwan were recruited. Participants were asked to fill in a structured questionnaire. For those who could not fill in the questionnaire, interviews were conducted. Sixty-four participants took western medicine (42.4%), 65 people (43.0%) used the combination of western and Chinese medicine and 22 (14.6%) used Chinese medicine only. Beliefs about the superiority of Chinese versus western medicine were associated with the patients' utilisation of those therapies. Patients using a combination of Chinese and western medicine had significantly better glycaemic control than patients using Chinese medicine alone. Further research is needed to clarify whether better glycaemic control was the result of the combined therapy, a higher motivation for self-care or both. Nevertheless, a combination of traditional and western medicine plays an important role and should not be ignored in controlling diabetes. However, the cost-effectiveness of such a plural therapy needs to be investigated.     

Ultrasound biomicroscopy of eyes undergoing deep sclerectomy with collagen implant.

AIMS--To assess the intraocular pressure (IOP) lowering mechanism of deep sclerectomy with collagen implant (DSCI), a non-penetrating glaucoma surgery. METHODS--Nine eyes of nine patients with medically uncontrolled open angle glaucoma underwent DSCI. Ultrasound biomicroscopy (UBM) of the sclerectomy site was performed 1 month after surgery. The following factors were assessed: length and height of collagen implant, and thickness of the residual trabeculocorneal membrane. RESULTS--Postoperative IOP decreased significantly in all nine eyes from a preoperative mean value of 25.8 (SD 4.8) mm Hg to a postoperative (1 month) mean value of 11.3 (6.3) mm Hg (p = 0.001). In all nine eyes, UBM at 1 month after surgery showed a subconjunctival filtration through the thin trabeculocorneal membrane and through the scleral flap around the collagen implant. In four cases, a hypoechoic area in the suprachoroidal space was observed and might represent ciliary body detachment or be due to suprachoroidal drainage of aqueous humour through the thin deep scleral wall. At 1 month after surgery the mean trabeculocorneal membrane thickness was 110.1 (16.8) microns, and the mean length and height of the collagen implant were 2.3 (0.1) mm and 1.1 (0.1) mm respectively. CONCLUSION--DSCI lowered IOP by allowing aqueous filtration through a thin trabeculocorneal membrane to the subconjunctival space and, eventually, to the suprachoroidal space.     

Exercise performance while wearing a tight-fitting powered air purifying respirator with limited flow

Sixteen subjects exercised at 80-85% of maximal aerobic capacity on a treadmill while wearing a tight-fitting, FRM40-Turbo Powered Air Purifying Respirator (PAPR). The PAPR was powered by a DC power supply to give flow rates of 0%, 30%, 66%, 94%, and 100% of rated maximum blower capacity of 110 L/min. As flow rate was reduced, so was performance time. There was a 20% reduction in performance time as blower flow changed from 100% to 0% of maximum. Significant differences in breathing apparatus comfort and facial thermal comfort were found as flow rate varied. It was concluded that inadequate blower flow rate decreases performance time, facial cooling, and respirator comfort.