A pharmacokinetic/pharmacodynamic/receptor binding model to predict the onset and duration of pharmacological activity of the benzodiazepines

1. 1. Ex vivo receptor binding as a function of time was determined in Charles River rats.

2. 2. The pharmacokinetic and protein binding parameters in man as well as the ex vivo receptor binding parameters in rat brain for three benzodiazepine induction agents, diazepam, lorazepam and midazolam, were used to develop and test a pharmacokinetic/ pharmacodynamic/receptor binding model.

3. 3. The model was subsequently used to predict changes in receptor binding and pharmaco-dynamics as a function of changes in pharmacokinetics.

4. 4. The model was found to be a good predictor of the relative onset and duration of the sedative and amnesic properties in normal subjects as well as in the presence of certain patho-physiological conditions and certain drug interactions.

人参皂甙Rb1和Rg1对小鼠中枢神经递质受体和脑内蛋白质合成的影响

应用放射配基结合法测定了人参皂甙Rb₁和Rg₁对α₁,α₂,β肾上腺素能受体、M胆碱能受体、5-羟色胺、多巴胺及GABA等七种受体的作用。结果均不能证明它们对这七种受体有亲和力。但给动物ip药物连续5天,Rb₁和Rg₁均能使中枢M胆碱受体密度显著增高。Rb₁及Rg₁还能显著增加脑内蛋白质的含量。上述实验结果对解释人参的中枢作用提供了重要证据。     

Osteoid osteoma: excision with scintimetric guidance

The definite diagnosis of osteoid osteoma relies on the demonstration of the nidus, best shown by CT, which also provides precise preoperative localization of the nidus. While bone-block excision to remove the nidus is feasible in the long bones, there may be unacceptable sequelae in the vertebral column and small bones of the hands. By precisely localizing the nidus, radionuclide scintimetry permits excellent therapeutic results, with minimal morbidity.     

Shoulder arthroscopy with the patient in the beach-chair position

We evaluated the use of the beach-chair, or sitting, position for arthroscopic shoulder surgery in 50 consecutive patients. Routine arthroscopy, arthroscopic subacromial decompression, and arthroscopic shoulder stabilizations were performed, with no complications. The advantages of this position include ease of setup, lack of brachial plexus strain because no traction is used, excellent intraarticular visualization for all types of arthroscopic shoulder procedures, and ease of conversion to the open approach if needed. The positioning technique is described.     

Nerve growth factor receptor immunoreactivity in the rat suprachiasmatic nucleus

Using a monoclonal antibody, nerve growth factor receptor has been immunohistochemically identified within the suprachiasmatic nucleus of adult rats. Labelling was most intense in the ventral, lateral and caudal portions of the nucleus and appeared primarily associated with fibers and terminals. These were among the most intensely labelled fibers and terminals in the forebrain.     

Intrauterine growth retardation: evaluation by magnetic resonance. Work in progress

Eleven high risk fetuses between 32 and 37 menstrual weeks gestational age were examined by magnetic resonance (MR) imaging. Serial obstetrical sonograms, birth weights, and serial postnatal examinations were obtained in all subjects. Sagittal MR spin echo images obtained using TR = 0.5 sec and TE = 28 msec were useful for assessing subcutaneous fat. Prospective estimates of fetal fat stores correlated with neonatal outcome better than sonographic measurements of fetal growth parameters or actual birth weight. MR appears to be a safe and useful technique that offers information complementary to obstetrical sonography when IUGR is suspected.     

Characterization of GMP-17, a granule membrane protein that moves to the plasma membrane of natural killer cells following target cell recognition.

Cytotoxic lymphocytes are characterized by their inclusion of cytoplasmic granules that fuse with the plasma membrane following target cell recognition. We previously identified a cytotoxic granule membrane protein designated p15-TIA-1 that is immunochemically related to an RNA-recognition motif (RRM)-type RNA-binding protein designated p40-TIA-1. Although it was suggested that p15-TIA-1 might be derived from p40-T1A-1 by proteolysis, N-terminal amino acid sequencing of p15-TIA-1 immunoaffinity purified from a natural killer (NK) cell line by using monoclonal antibody (mAb) 2G9 revealed that p15-T1A-1 is identical to the deduced amino acid sequence of NKG7 and GIG-1, cDNAs isolated from NK cells and granulocyte-colony-stimulating factor-treated mononuclear cells, respectively. Epitope mapping revealed that mAb 2G9 recognizes the C terminus of p15-T1A-1 and p40-T1A-1. The deduced amino acid sequence of p15-T1A-1/NKG7/GIG-1 predicts that the protein possesses four transmembrane domains, and immuno-electron microscopy localizes the endogenous protein to the membranes of cytotoxic granules in NK cells. Given its subcellular localization, we propose to rename-this protein GMP-17, for granule membrane protein of 17 kDa. Immunofluorescence microscopy of freshly isolated NK cells confirms this granular localization. Target cell-induced NK cell degranulation results in translocation of GMP-17 from granules to the plasma membrane, suggesting a possible role for GMP-17 in regulating the effector function of lymphocytes and neutrophils.