Pharmacodynamic Comparison of a Nasal Formulation of Verapamil and Intravenous and Oral Dosage Forms

The nasal route has been shown to be effective for the administration of numerous drugs in order to improve drug bioavailability. A nasal gel of verapamil hydrochloride was formulated and evaluated pharmacodynamically in humans, using electrocardiographic results, with comparison to oral and IV routes. Seven volunteers were involved in the study and the pharmacodynamic parameters were evaluated statistically. Experimental nasal gel showed similar pharmacodynamic results with the intravenous route, which is a hint to the reduction in verapamilinduced first-pass metabolism. However, oral route of administration showed a tendency of less efficacy. No reasonable effect of verapamil could be obtained with the placebo group.     

Highly reliable testing of ULSI memories with on-chip voltage-downconverters

Two testing techniques for ultra-large-scale integrated (ULSI) memories containing on-chip voltage downconverters (VDCs) are described. The first in an on-chip VDC tuning technique that adjusts internal V_CC to compensate for the monitored characteristics of the process parameters during repair analysis testing. The second is an operating-voltage margin test, performed at various internal V_CC levels during the water sort test (WT) and the final shipping test (FT)     

Computer analysis,design and simulation of horizontal ground heat exchangers

This paper presents a new computerized procedure for dealing with the design of horizontal ground heat exchangers (HGHE). The computer program is based on the transient model of coupled nonlinear partial differential equations governing heat and mass flow in soils. The model is two-dimensional and delineates the operation of ground heat storage with the HGHE and such phenomena as freezing/thawing and drying/rewetting of soil moisture. Comprehensive climatological data, such as ambient temperature, solar radiation, wind velocity, rainfall, snowfall, snow characterstics, and water vapour pressure is used to simulate conditions at the ground surface over any required length of time. The package can be applied to any geographical location by changing climatic and soil data input. The designer has the possibility of selecting any of 12 types of soils from sand to clay, 12 commercial heat pumps, nine different configurations of the HGHE, 16 plastic pipes for ground coils, and 13 ground coil fluids. The program, however, does not calculate the length of the HGHE but it evaluates the thermodynamic performance of a ground heat pump system and provides comprehensive data on thermal and hydraulic conditions in ground heat storage. The length of the ground heat exchanger is obtained from a line source theory model or from site dimensions and pipe spacing. Computed results for ground heat exchanger operation correlate fairly well with experimental data. Simulation of temperature and moisture content in the ground for natural conditions (no heat extraction/deposition) showed a fair agreement with field data. The entire computer program is user-friendly, interactive, menu-driven, and written in FORTRAN 77.     

Multi-emitter Si/GexSi1-x heterojunctionbipolar transistor with no base contact and enhanced logic functionality

We demonstrate multi-emitter Si/Ge_xSi_1-x n-p-n heterojunction bipolar transistors (HBT's) which require no base contact for transistor operation. The base current is supplied by the additional emitter contact under reverse bias due to the heavy doping of the emitter-base junction. Large-area HBT test structures exhibit good transistor characteristics, with current gain β≈400 regardless of whether the base current is supplied by a test base electrode or one of the emitter contacts. These devices have enhanced logic functionality because of emitter contact symmetry. Since device fabrication does not require base electrode formation, the number of processing steps can be reduced without significant penalty to HBT performance     

Discriminative stimulus properties of ethanol in the rat: differential effects of selective and nonselective benzodiazepine receptor agonists

Rats were trained to discriminate between ethanol (1.0 g/kg; 10% v/v) and saline under a fixed ratio 10 schedule of sweetened milk reinforcement. Both diazepam [nonselective, full benzodiazepine (BZ) receptors agonist] and bretazenil (nonselective, partial BZ receptor agonist) produced dose-dependent ethanol-appropriate responding (>75%). Neither diazepam nor bretazenil affected the response rate at the doses producing maximal generalisation from ethanol. In contrast, zolpidem (full BZ1 receptor agonist) and abecarnil (full BZ1/full or partial BZ2 receptor agonist) produced only moderate (<50%) ethanol-appropriate responding when tested up to doses that markedly decreased the overall response rate. These results suggest that: 1) there are no major differences between full and partial, nonselective BZ receptor agonists in their ability to substitute for 1.0 g/kg dose of ethanol; 2) stimulation of BZ1 receptors alone is not sufficient to produce ethanol-like discriminative stimulus effects in the rat.     

Role of provocation poliomyelitis in vaccine-associated poliomyelitis

BACKGROUND: Laparoscopic gastrostomy as an alternative to open gastrostomy was introduced with various technical variants 5 years ago. However, long-term results of these new methods are still lacking. METHODS: From 4/1993 to 2/1996, laparoscopic gastrostomies were performed on 42 patients (50.9 +/- 15.6 [24-71] years) with esophageal stenosis in locally advanced hypopharyngeal (17 patients) or oropharyngeal (nine patients) carcinoma, incurable esophageal carcinoma (13 patients) and cerebral dyspagia (three patients). Operating time was 38 +/- 11 min [15-65 min]. Procedure-related mortality was 0%. Major complications occurred in 2/42 (4.7%) patients; minor complications were found in 4/42 (9.4%) patients. During a total usage time of 427 months, 14 stoma infections occurred (0.11 infections/100 days). CONCLUSION: Laparoscopic gastrostomy allows a safe, fast, and cheap reestablishment of enteral nutrition. The procedure is minimally invasive and can also be performed under local anesthesia. It has become our method of choice in patients with malignant, nonresectable subtotal stenosis of the hypopharynx or esophagus.     

Ultralow-voltage boron-doped diamond field emitter vacuum diode

A boron-doped diamond field emitter diode with ultralow turn-on voltage and high emission current is reported. The diamond field emitter diode structure with a built-in cap was fabricated using molds and electrostatic bonding techniques. The emission current versus anode voltage of the capped diamond emitter diode with boron doping, sp² content, and vacuum thermal electric (VTE) treatment shows a very low turn-on voltage of 2 V. A high emission current of 1 μA at an anode voltage of less than 10 V can be obtained from a single diamond tip. The turn-on voltage is significantly lower than comparable silicon field emitters     

Stem cells in prostatic epithelia

The normal prostate is, structurally and functionally, a highly complex glandular tissue in which populations of epithelial and stromal cells interact, one with the other, and are under a constant state of proliferation, differentiation, elimination and selective secondary replenishment so that functional integrity of the tissue is maintained. The ability of normal prostatic tissue to maintain its structure and function is dependent upon retention of cells, generally regarded as 'stem cells', which are able to respond by proliferation and selective differentiation within a wide range of phenotypic alternatives. With respect to cells in the epithelial compartment, replenishment is possible at several levels from within distinct pathways of normal cellular differentiation. It is now appreciated that fully differentiated prostatic epithelial cells retain a far greater degree of phenotypic 'plasticity' than was earlier apparent from morphological examination of the intact tissue. This inherent plasticity, coupled with the ability of the intact tissue to respond to diverse environmental (particularly humoral) stimuli by regenerating a wide and divergent spectrum of functional prostatic epithelial phenotypes is its strength--but also its weakness. Disturbance and distortion of the homeostatic regulatory mechanisms, whether physical or humoral, which control the normal sequence of epithelial proliferation, differentiation and elimination exposes these cells, particularly multipotent 'stem cells', to an increased probability of genetic change, thus resulting in either transient, or permanent, neoplastic transformation.     

Integrins and inside-out signal transduction: converging signals from PKC and PIP3

Recent studies have identified molecules that interact with integrins and appear to participate in the signaling pathways that regulate integrin adhesiveness. Clues provided by studies of these molecules point to the integration by integrins of signal transduction pathways implicated in cell division and activation.