Developing a conceptual framework and a tool for measuring access to, and use of, medicines at household level (HH-ATM tool).

OBJECTIVE: To develop a valid and reliable tool to evaluate access to, and use of, medicines at household level (HH-ATM tool). STUDY DESIGN: The Behavioral Model of Health Services Use was adapted and used as the conceptual framework for developing the HH-ATM tool. Questionnaires were designed (individual and household) based on the conceptual framework and existing tools, including items that captured the characteristics of predisposing, enabling and need factors; health care behaviours; outcomes and impacts. METHODS: Face validity, content validity and test-retest reliability were assessed using inter-rater agreement, item and scale content validity indices, comprehensiveness indices, and intra-class correlation, kappa and weighted-kappa coefficients. RESULTS: The household and individual questionnaires demonstrated appropriate validity and reliability. The content validity of household questionnaire was favourable, with inter-rater agreement of 86% and 91% for relevance and clarity, respectively. Scale content validity indices for relevance and clarity were 89% and 91%, respectively, and comprehensiveness was scored at 100%. These indices were also favourable for the individual questionnaire, all scoring 94% or higher. CONCLUSION: The questionnaires showed excellent validity and reliability for use in Iran. The HH-ATM tool can be implemented to evaluate access to, and use of, medicines in Farsi-speaking communities, and may be useful in other communities if adapted appropriately.

Gabapentin Enhances Neurogenesis in E14 Rat Embryonic Neocortex Stem Cells.

Many anticonvulsant drugs have been studied for their non conventional therapeutic effects on neurodegerative diseases but merely a few demonstrated potential neurogenic characteristic. Gabapentin as a well-known mood stabilizer was studied for its potential capability to promote neurogenesis in embryonic rat cortical stem cells. Rat E14 cortical stem cells were exposed to gabapentin during differentiation for 7 days and subjected to immunocytochemistry. The phenotypic changes were evaluated in the ultimately survived and differentiated cells. Gabapentin (16 µg/ml) exposure significantly increased the number and percentage of MAP2 immunopositive neurons with no significant alterations in nestin or GFAP immunopositivity in neural or glial progenitors. The enhanced number of neurons by therapeutic doses of gabapentin via augmentation of the neuronal differentiation in neural stem cells may participate to the therapeutic properties of gabapentin in the treatment of mood disorder.

The dilemma of hyperoxia following positive pressure mechanical ventilation: role of iron and the benefit of iron chelation with deferasirox.

BACKGROUND AND OBJECTIVE: Increased oxidative stress in patients under treatment with high concentrations of oxygen (hyperoxia) is considered to be one of the major mechanisms of lung injury, which is thought among different mediators, transition metal ion, iron, by generation of very reactive free radicals which play an important role. Disruption of normal iron homeostasis has been reported in hyperoxic conditions. We hypothesized that chelation of iron can reduce hyperoxia-induced lung injury. METHODS: Mechanically ventilated patients, who received oxygen with FiO2 >0.5 for at least 3 days, underwent bronchoscopy before and 72 hours after receiving "Deferasirox". Oxidative injury index and iron homeostasis markers were measured in lavage fluid and plasma. RESULTS: In 12 patients, the concentrations of 8-isoprostane (p=0.005), 8-oxoguanine (p=0.04), carbonyl proteins (p=0.04)--as markers of oxidative stress--decreased significantly in lavage fluid after intervention. Levels of iron-related proteins, ferritin (p=0.04) and transferrin (p=0.005) also decreased significantly in lavage fluid. CONCLUSION: Deferasirox--as an iron chelator--decrease oxidative injury index in hyperoxic condition and it could be consider safe and beneficial agent, along with other supportive measures in hyperoxia-induced lung injury for better toleration of oxygen therapy.

Restoration of morphine-induced alterations in rat submandibular gland function by N-methyl-D-aspartate agonist.

The effects of morphine, 1-aminocyclobutane-cis-1,3-dicarboxylic (ACBD; NMDA agonist) and 3-((R)2-carboxypiperazin-4-yl)-propyl-l-phosphoric acid (CPP; NMDA antagonist) and their concurrent therapy on rat submandibular secretory function were studied. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Intraperitoneal injection of morphine (6 mg/kg) induced significant inhibition of salivary flow rate, total protein, calcium, and TGF-beta1 concentrations. Administration of ACBD (10 mg/kg) and CPP (10 mg/kg) alone did not influence secretion of submandibular glands. In combination therapy, coadministration of CPP with morphine did not influence morphine-induced changes in salivary function while ABCD could restore all morphine-induced changes. In combination treatment, ACBD prevented morphine-induced reduction of flow rate, total protein, calcium, and TGF-beta1 and reached control levels. It is concluded that morphine-induced alterations in submandibular gland function are mediated through NMDA receptors.

Rapid high-performance liquid chromatographic method for determination of doxycycline in human plasma.

A simple, rapid and precise analytical method for determination of doxycycline in human plasma is described. A high-performance liquid chromatography (HPLC) system based on a mbondapak C18 column (300 mm x 4.6 mm i.d., 10 microns) and a UV detector (lambda = 347 nm) were used. A mixture of actonitrile 0.1 M potassium dihydrogen phosphate buffer (35:65 v/v) adjusted to pH 3 was used as mobile phase. The proteins were precipitated with a 24% perchloric acid aqueous solution. The detection limit for doxycycline in plasma was 3 ng mL-1. The average recovery was about 96%. The method is simple, sensitive and suitable for pharmacokinetic studies of doxycycline. The inter-day and intra-day assay coefficients of variation were found to be less than 8%.

Selective liquid chromatographic method for determination of fluoxetine in plasma.

A selective and sensitive liquid chromatographic method was developed for the determination of fluoxetine (FLU) in plasma. FLU was isolated from plasma by liquid-liquid extraction. The chromatographic separation was performed on an analytical 250 x 3.9 mm id Novapak C18 column (4 microm particle size) with an isocratic mobile phase consisting of phosphate buffer-acetonitrile-methanol -triethylamine (58 + 30 + 10 + 2, v/v) adjusted to pH 7. Using UV detection at 226 nm, the detection limit for FLU in plasma was 3 ng/mL. No interferences were found with tricyclic antidepressant drugs, which allows this method to be used in clinical studies. The calibration curve was linear over the concentration range of 10-200 ng/mL. The average recovery was about 80% for plasma. The inter- and intraday assay coefficients of variation were <8%.

Effects of chronic lithium on ototoxicity induced by gentamicin and amikacin in guinea-pigs.

The effects of chronic lithium co-therapy on the expression of gentamicin and amikacin ototoxicity were tested in guinea-pigs. Intramuscular injection of different doses of gentamicin (5, 10 mg/kg/day) and amikacin (150, 300 mg/kg/day) for three weeks, induced hearing loss consistent with the established pattern of aminoglycoside ototoxicity. Lithium salts remains one of the most widely used treatment for depressive illness. Administration of lithium chloride (600 mg/l, 35 days) in drinking water changed auditory brainstem response in a time-dependent manner. Pretreatment of animals with lithium chloride after seven days induced significant alterations in wave latency and interval. The present study assesses the protective effects of chronic lithium on gentamicin-induced ototoxicity in guinea pig. The results suggest that duration of lithium administration may be involved in auditory brainstem response changes and the observations could be accounted for, at least partially, by lithium- and aminoglycosides-induced perturbations of the phosphoinositide cascade within the inner ear.

Effect of granisetron on morphine-induced analgesia in mice by formalin test.

1. In this investigation, the influence of a selective 5HT3 antagonist, granisetron, on morphine-induced antinociception in the formalin test has been studied. There is evidence that the 5HT3 receptor system takes part in analgesic response. 2. Male albino mice weighing 22-27 g were used in the experiments. All drugs were administered 30 min before formalin injection. Comparison between groups was made by analysis of variance and then Newman-Keuls test. 3. Different doses of morphine (1.5-9.0 mg/kg) subcutaneously induced antinociception in both phases of the formalin test. 4. Coadministration of granisetron (0.1-10.0 mg/kg) intraperitoneally had no effect on morphine analgesia, but granisetron injection alone induced dose-dependent analgesia in both phases of the formalin test. 5. Results of this study suggest a role for a new selective 5HT3 antagonist in analgesia.

Alterations of physostigmine-induced yawning by chronic lithium administration in rats.

The effect of chronic lithium pretreatment on physostigmine-induced yawning was investigated in male rats. Intraperitoneal administration of physostigmine to rats induced yawning in a biphasic manner. However the maximum response was obtained by 0.2 mg/kg of the drug. Intracerebroventricular administrations of a putative M1 and M2 muscarinic receptor antagonists, pirenzepine and methoctramine decreased physostigmine-induced yawning. Intraperitoneal administration of a non-selective muscarinic receptor antagonist, atropine, also decreased the physostigmine-induced yawning significantly. Chronic lithium pretreatment (30 days) reduced yawning induced by physostigmine. The inhibitory effect of pirenzepine, methoctramine and atropine on physostigmine-induced yawning increased in rats pretreated with chronic lithium. These findings indicate that yawning is induced by a central cholinergic mechanism and that chronic pretreatment of lithium may interact with the cholinergic-induced behaviour.