In Memoríam

Animal experiments having indicated a nearly twofold increase in anticonvulsant protection with the use of diuretics which increase blood-brain barrier permeability, the principle was applied to treatment of humans with epilepsy. The addition of diuretics to anticonvulsant medication permitted a decrease of previously toxic dosages in ten epileptics, followed for six months, without lessening (and in some cases improving) the control of seizures. In three cases excessive diuresis and gastric distress necessitated discontinuance or decrease in dosage of the diuretic used.     

In Memoríam

Three hundred patients with the post-thrombophlebitic syndrome were studied. The lower extremities were involved in the majority of cases. Severe disabling subjective symptoms, such as burning, aching, cramping and shooting pains, occurred in approximately 15 per cent of cases regardless of the presence or absence of objective findings such as ulcerations, edema or dermatitis. Subjective symptoms occurred in about as many men as women. The persistence and severity of disabling subjective symptoms seemed to be unrelated to the possibility of compensation or pecuniary gain. No adequate explanation could be found for the perseverance of disabling subjective symptoms. There was no consistent relation of subjective symptoms and disability to psychic factors.     

In Memoríam

Mental retardation is a symptom of an underlying disease process. In California state hospitals for the retarded an accurate dynamic diagnosis is possible through utilizing the knowledge of neurology, psychiatry, pediatrics, psychology, social service, rehabilitation, education, the laboratory and trained psychiatric technicians. A program of "custody" is archaic and we are returning to the concept of training, treatment, and turnover. This kind of program is essential in order to avoid building new hospitals at the cost of millions of dollars every few years.Parent organizations for retarded children are expanding in ever increasing number. Special education programs in public schools, foster care homes and sheltered workshops may make admission to hospitals unnecessary and aid return of patients to the community.     

In Vitro–In Vivo Correlation of Efavirenz Tablets Using GastroPlus®

The aim of the present work was to use GastroPlus™ software for the prediction of pharmacokinetic profiles and in vitro–in vivo correlation (IVIVC) as tools to optimize the development of new generic medications. GastroPlus™ was used to simulate the gastrointestinal compartment and was based on the advanced compartmental absorption and transit model. Powder dissolution and efavirenz tablet dissolution studies were carried out to generate data from which correlation was established. The simulated plasma profile, based on the physicochemical properties of efavirenz, was almost identical to that observed in vivo for biobatches A and B. A level A IVIVC was established for the dissolution method obtained for the generic candidate using the Wagner–Nelson (r² = 0.85) and for Loo–Riegelman models (r² = 0.92). The percentage of fraction absorbed indicated that 0.5% sodium lauryl sulfate may be considered a biorelevant dissolution medium for efavirenz tablets. The simulation of gastrointestinal bioavailability and IVIVC obtained from immediate-release tablet formulations suggests that GastroPlus™ is a valuable in silico method for IVIVC and for studies directed at developing formulations of class II drugs.KEY WORDS: bioavailability, computational simulation, efavirenz, GastroPlus™, in vivo–in vitro correlation     

Developing In Vitro–In Vivo Correlation of Risperidone Immediate Release Tablet

The present study was aimed to predict the absorption profile of a risperidone immediate release tablet (IR) and to develop the level A in vitro–in vivo correlation (IVIVC) of the drug using the gastrointestinal simulation based on the advanced compartmental absorption and transit model implemented in GastroPlus™. Plasma concentration data, physicochemical, and pharmacokinetic properties of the drug were used in building its absorption profile in the gastrointestinal tract. Since the fraction absorbed of risperidone in simulation was more than 90% with low water solubility, the drug met the criteria of class II of the Biopharmaceutics Classification System. The IVIVC was developed based on the model built using the plasma data and the in vitro dissolution data in several dissolution media based on the Japanese Guideline for Bioequivalence Studies of Generic Products. The gastrointestinal absorption profile of risperidone was successfully predicted. A level A IVIVC was also successfully developed in all dissolution media with percent prediction error for Cmax and the area under the curve less than 10% for both reference and test drug.Key words: GastroPlus™, immediate release tablet, in vitro–in vivo correlation, risperidone     

Gasping Generation in Developing Swiss–Webster Mice In Vitro and In Vivo

During hypoxia the respiratory network produces gasping in vivo and in vitro. To understand the mechanisms involved in such response and to validate in vitro findings, correlative studies are necessary. During perinatal age gasping generation is robust and then declines during postnatal development, possibly due to changes in either the rhythm generator (the pre-Bötzinger complex, PBC) and/or its motor outputs. We tested this hypothesis by recording respiratory response to hypoxia in vivo and in vitro during postnatal development. We found that postnatal age influences: (1) The hypoxia-induced pattern change in the PBC bursts, (2) The coupling between the PBC and the XII nucleus during prolonged hypoxia and (3) The ability of mice to gasp and autoresuscitate from hypoxic conditions. We conclude that the inability of mice to gasp during late postnatal development might be determined by a progressive uncoupling between the respiratory rhythm generator and its motor outputs in hypoxia.     

新的In Situ PCR系统

Perkin-Eliner介绍了GeneAmp In Situ PCR System,声称这是第一个用于可重复in situ聚合酶链反应(PCR)的完整系统。该系统在玻璃载玻片上完成PCR,无需抽提DNA。GeneAmp System具有一个高输出热循环仪,循环仪上的垂直10-玻片样品盒很有创意。一个循环最多可扩增30个样品。该