A radioimmunoassay for serum calcitonin in the rat

Persisting primitive papilla epithelialis is described in a 22-year-old woman. The papilla has blurred borders, a central papilla eminence and a yellowish colour. In addition pigmentary pseudoretinopathy with perivascular pigment deposits and hypermetropia with aplasia maculae occurred. This picture can be confused classically with pappilloedema.     

Long acting methadone

Tablets were prepared using pan-coating, congealing, plasticization with organic solvents and direct compression methods. The tablets were evaluated using the official dissolution test, and an analysis of the active ingredient was accomplished by employing gas-liquid chromatography. The formulation and dissolution characteristics of sustained release tablets, employing the matrix concept to regulate drug release, were studied. Particle size distribution of plastic material influenced the release rates from porous inert matrices, and it was found that incomplete drug release occurred from these preparations. Three-layer slowly-eroding sustained release tablets, using a swellable gum (carbomer) were formulated; by adjusting the proportion of the gum quantitative release of the drug was attained. Approximation of linearity for drug release-time relationship was achieved from three-layer slowly-eroding tablets containing different concentrations of drug in the middle and outer layers. Administration of the above tablets, containing 30 mg of methadone, produced analgesia in male albino rats for approximately 60 h, without undesirable effects.     

Intracellular delivery of a cytolytic T-lymphocyte epitope peptide by pertussis toxin to major histocompatibility complex class I without involvement of the cytosolic class I antigen processing pathway

A CD8(+) cytolytic T-lymphocyte (CTL) response to antigen-presenting cells generally requires intracellular delivery or synthesis of antigens in order to access the major histocompatibility complex (MHC) class I processing and presentation pathway. To test the ability of pertussis toxin (PT) to deliver peptides to the class I pathway for CTL recognition, we constructed fusions of CTL epitope peptides with a genetically detoxified derivative of PT (PT9K/129G). Two sites on the A (S1) subunit of PT9K/129G tolerated the insertion of peptides, allowing efficient assembly and secretion of the holotoxin fusion by Bordetella pertussis. Target cells incubated with these fusion proteins were specifically lysed by CTLs in vitro, and this activity was shown to be MHC class I restricted. The activity was inhibited by brefeldin A, suggesting a dependence on intracellular trafficking events, but was not inhibited by the proteasome inhibitors lactacystin and N-acetyl-L-leucyl-L-leucyl-L-norleucinal (LLnL). Furthermore, the activity was present in mutant antigen-presenting cells lacking the transporter associated with antigen processing, which transports peptides from the cytosol to the endoplasmic reticulum for association with MHC class I molecules. PT may therefore bypass the proteasome-dependent cytosolic pathway for antigen presentation and deliver epitopes to class I molecules via an alternative route.     

Ventricular pressure slope and bileaflet mechanical heart valve closure

The maximum left ventricular pressure slope (dP/dt) value has been used by several investigators as the criterion for studying mitral valve closure. In this article, the relationship between the ventricular pressure slope (dP/dt) and the leaflet closing behavior of bileaflet mechanical heart valves (BMV) is investigated. Two current BMVs, the St. Jude Medical 29 mm and CarboMedics 29 mm, installed in the mitral position of a mock circulatory pulsatile flow loop were used as the study model. Under simulated physiologic pressures and flow conditions, the experiment was conducted at 70, 90, and 120 beats/min with corresponding flow rates of 5.0, 6.0, and 7.5 liters/min, respectively. A laser sweeping technique was used to monitor the leaflet closing motion within the last 3 degrees excursion at valve closure. A modified dual beam laser sweeping technique system was used to register the difference of leaflet/housing impact time between the two BMV closing leaflets in asynchronous closure. Common BMV asynchronous closures were found in both BMVs at all three heart rates tested. The second closing leaflet was found to always close at higher velocity than the first. Simultaneous measurements of the ventricular pressure (Pv) and the leaflet closing time showed that Pv exhibited three stage characteristics. In the first stage, Pv gradually increased as the ventricle was filled. A sudden rise of Pv occurred immediately after closing of the first leaflet. The maximum dp/dt occurred in the third stage after closure of both BMV leaflets. The BMV closing behavior and the corresponding Pv pattern were found to depend strongly upon valve type and heart rate. The time averaged ventricular pressure slope (dp/dt) values at 70, 90, and 120 beats/min were about 40, 70, and 150 mmHg/sec for the St. Jude Medical valve and 40, 105, and 205 for the CarboMedics valve during the first closing stage. The maximum dp/dt values were 2670, 4350, and 5000 mmHg/sec for the St. Jude Medical valve and 1210, 2530, and 3210 mmHg/sec for the CarboMedics valve at the three heart rates tested, respectively. The study showed that the left ventricular pressure patterns (dP/dt) at valve closure were the result of valve operation under given driving conditions. The dp/dtmax cannot be used as the criterion for studying BMV closure.