顺铂聚乳酸微球的药物释放特性及肝动脉栓塞研究

对顺铂聚乳酸微球进行了体外药物释放和家犬肝动脉栓塞研究。该微球粒径范围为50～200μm,平均粒径为115.76±35.94μm,顺铂含量为37.16%(W/W);体外药物释放机制符合Higuchi方程;肝动脉栓塞后8h,肝组织顺铂浓度高达21.55±12.18μg/g,明显高于肝动脉灌注顺铂组:3.16±0.09μg/g(P<0.05);肝动脉栓塞组的顺铂血浓峰值、各取血点浓度及曲线下面积AUC皆低于肝动脉灌注顺铂组。可望达到提高栓塞部位的药物疗效,降低全身毒副反应的作用。     

Primary tuberculous nasal polypi—A case report

Primary tuberculous pathology in nasolpolypi is a rare condition. A case of bilateral ethmoidal polypi with tubercular lesion diagnosed on histopathologlcal examination is being reported and the available relevant literature has been reviewed.     

CNS 7056: A Novel Ultra-short-acting Benzodiazepine

Background: A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile. This goal has been achieved by rendering the compound susceptible to metabolism via esterases. The authors now report on the profile of CNS 7056 in vitro and in vivo.

Methods: The affinity of CNS 7056 and its carboxylic acid metabolite, CNS 7054, for benzodiazepine receptors and their selectivity profiles were evaluated using radioligand binding. The activity of CNS 7056 and midazolam at subtypes ([alpha]1[beta]2[gamma]2, [alpha]2[beta]2[gamma]2, [alpha]3[beta]2[gamma]2, [alpha]5[beta]2[gamma]2) of the [gamma]-aminobutyric acid type A (GABAA) receptor was evaluated using the whole cell patch clamp technique. The activity of CNS 7056 at brain benzodiazepine receptors in vivo was measured in rats using extracellular electrophysiology in the substantia nigra pars reticulata. The sedative profile was measured in rodents using the loss of righting reflex test.

Results: CNS 7056 bound to brain benzodiazepine sites with high affinity. The carboxylic acid metabolite, CNS 7054, showed around 300 times lower affinity. CNS 7056 and CNS 7054 (10 [mu]m) showed no affinity for a range of other receptors. CNS 7056 enhanced GABA currents in cells stably transfected with subtypes of the GABAA receptor. CNS 7056, like midazolam and other classic benzodiazepines, did not show clear selectivity between subtypes of the GABAA receptor. CNS 7056 (intravenous) caused a dose-dependent inhibition of substantia nigra pars reticulata neuronal firing and recovery to baseline firing rates was reached rapidly. CNS 7056 (intravenous) induced loss of the righting reflex in rodents. The duration of loss of righting reflex was short (< 10 min) and was inhibited by pretreatment with flumazenil.     

Effects of instruction by practice assistants on inhaler technique and respiratory symptoms of patients. A controlled randomized videotaped intervention study

BACKGROUND: Many patients with asthma or chronic obstructive pulmonary diseaseuse their medication inhalers incorrectly. General practitioners,pharmacists and other health care providers do not always havethe opportunity to instruct patients in correct inhaler technique. OBJECTIVE: To find out whether the inhaler technique and respiratory symptomsof patients can be improved after instruction by practice assistants. METHODS: Single blind, randomized intervention study in which 48 patientswho had been using a dry powder inhaler for at least one monthtook part. Their inhaler technique was videotaped on two visitswith a two-week interval between visits. The inhaler techniqueon the videos was subsequently scored by two experts on ninecriteria. At both visits the patients completed a questionnaireabout their respiratory symptoms. After the first video, 25patients were randomly chosen to receive instruction from oneof six practice assistants who had followed a one evening courseabout inhaler instruction, and who had been issued an instruction-set. RESULTS: The patients who received instruction had a significantly greaterreduction in number of mistakes at the second visit than thepatients who did not (P = 0.01). The instructed patients alsoreported less dyspnoea at the second visit (P = 0.03). No effectof instruction was found on wheezing, cough and sputum production. CONCLUSION: The inhaler technique of patients can be improved significantlyby the instruction of patients by trained practice assistants,possibly resulting in less dyspnoea. Keywords. Administration-inhalation, obstructive lung diseases, airways symptoms, patient-education, general practice.     

Chronic Administration of Glucocorticoids Directly Upregulates Prepro-Neuropeptide Y and Y1-Receptor mRNA Levels in the Arcuate Nucleus of the Rat

The complete sequence of the cDNA encoding the neuropeptide Y (NPY) Y₁-receptor has recently been deduced from a rat brain library, and the presence of messenger ribonucleic acid (mRNA) encoding Y₁-receptor protein has been demonstrated within the brain. Using quantitative in situ hybridization histochemistry, the content and distribution of Y₁receptor and preproNPY mRNAs have been investigated in the hypothalamic arcuate nucleus of adrenalectomized rats receiving glucocorticoid replacement therapy for 12 days by means of either high doses of dexamethasone in their drinking water or by subcutaneous corticosterone pellets. Basal metabolic parameters such as weight gain or loss, blood glucose and plasma insulin were monitored: Dexamethasone treatment induced weight loss and a state of hyperinsulinemia with normoglycemia, while corticosterone treated animals displayed metabolic parameters identical to sham ADX animals. Within the arcuate nucleus of glucocorticoid treated animals, levels of Y₁receptor and preproNPY mRNAs were increased. In contrast, adrenalectomy itself had no effect upon Y₁-receptor mRNA levels or preproNPY mRNA levels in the arcuate nucleus. These studies demonstrate that glucocorticoids exert a stimulatory action on levels of Y₁-receptor mRNA and preproNPY mRNA levels in the hypothalamic arcuate nucleus. This is the first evidence to suggest that the expression of a neuropeptide-receptor gene in the central nervous system may be directly sensitive to peripheral hormonal signals.