Application of the hot-wire anemometer to respiratory measurements in small animal.

A hot-wire anemometer was evaluated to determine its suitability for measurement of small tidal volumes. Used with a constant background flow of gas, the output of the hot-wire anemometer was linear and independent of respiratory frequency, temperature, and humidity. The change in output with CO2 concentration was negligible within the physiologic range. The use of a background flow eliminates the need for one-way valves, minimizes dead space, and maintains the flow velocity past the hot wire within its range of linear response.     

A novel high resolution micro-radiotherapy system for small animal irradiation for cancer research

Micro-radiotherapy (micro-RT) system is specially designed for small animal (cancer cell) irradiation for basic and translational cancer research. We use carbon nanotube (CNT) field emission technology to develop a novel micro-RT system for image-guided high precision irradiation that is similar to the state of the art radiotherapy which our cancer patients receive today at mouse scale. Through the field emission control of its individually addressable x-ray pixel beams the micro-RT system electronically shapes the radiation field and forms intensity modulation pattern. In this paper, we present the development of a carbon nanotube field emission cathode array chip--a key component for our novel micro-RT system. The prototype micro-RT CNT field emission cathode array chip has 5 x 5 individually addressable cathode pixels that are 1 mm in diameter and 2 mm in pitch. An individual CNT cathode pixel is predicted to generate a dose rate in the order of 100 cGy/min at the center of the irradiated mouse based on our Monte Carlo simulation. The temporal and spatial resolutions of the micro-RT system are expected to be approximately ms level and < 2 mm respectively.     

New respiratory gas valve support for graded exercise studies.

We describe a new support structure for respiratory gas valves for use in exercise studies. Use of this structure largely avoids problems of large inertial reactions and feelings of confinement on the part of the subject which have characterized previous systems. The support mechanism consists of a spring-reacted, pivoted boom carried on the end of a counterbalanced swinging beam. This device was designed for use on an adjustable slope motor-driven treadmill, but may be adapted to a variety of other experimental arrangements.     

A respiratory valve for rapid switching between two gas mixtures.

We have devised a respiratory valve that facilitates rapid and silent breath-to-breath switching between two gas mixtures, under remote control. It utilizes two inspiratory Loven-type valve elements, one for each gas mixture, either of which can be held closed with an electromagnet. Any type of valve element can serve as the expiratory valve. We have used a small respiratory valve with goats and a larger model for both goat and human use.     

An integrated database for managing animal study proposals and animal inventory for the small animal facility

The authors describe how they created a user-friendly, multifunctional database for use by a variety of vivarium staff.     

Towards a small animal model for hepatitis C

Hepatitis C virus (HCV) causes chronic liver disease and affects an estimated 3% of the world's population. Options for the prevention or therapy of HCV infection are limited; there is no vaccine and the nonspecific, interferon‐based treatments now in use are frequently ineffective and have significant side effects. A small‐animal model for HCV infection would significantly expedite antiviral compound development and preclinical testing, as well as open new avenues to decipher the mechanisms that underlie viral pathogenesis. The natural species tropism of HCV is, however, limited to humans and chimpanzees. Here, we discuss the prospects of developing a mouse model for HCV infection, taking into consideration recent results on HCV entry and replication, and new prospects in xenotransplantation biology. We highlight three independent, but possibly complementary, approaches towards overcoming current species barriers and generating a small‐animal model for HCV pathogenesis.     

An anesthetic system for small laboratory animals.

A non-rebreathing anesthetic system for administering volatile anesthetic mixtures to small laboratory animals was designed. The device is easily constructed and simple to operate, yet permits the anesthetic management of small animals by technics similar to those used for man and larger species.     

Ultracentrifugation micromethod for preparation of small experimental animal lipoproteins

Sequential flotation ultracentrifugation is commonly used in the preparation of plasma lipoproteins. However, protocols often require prolonged centrifugation time (48-72 h) and large plasma volumes (2-20 ml), which makes them unsuitable for studies on small laboratory animals. Although analytical techniques such as FPLC have often small sample requirements, further fraction analysis is often limited to the small fraction volume obtained. A sequential ultracentrifugation micromethod is described to obtain rat lipoprotein fractions from 400 microl of plasma in a cumulative centrifugation time of 7.5 h. Fraction volumes were determined and densities were adjusted to those of rat plasma lipoproteins. Polyacrylamide gel electrophoresis and enzymatic measurements of triglycerides, total cholesterol, and phospholipids were used to assess the purity of the lipoprotein fractions. The results were compared with those obtained from a classical sequential ultracentrifugation protocol. The micromethod presented here can be further adapted to other experimental animal species with little modifications.     

Use of a sentinel system for field measurements of Cryptosporidium parvum oocyst inactivation in soil and animal waste

A small-volume sentinel chamber was developed to assess the effects of environmental stresses on survival of sucrose-Percoll-purified Cryptosporidium parvum oocysts in soil and animal wastes. Chambers were tested for their ability to equilibrate with external chemical and moisture conditions. Sentinel oocysts were then exposed to stresses of the external environment that affected their viability (potential infectivity), as indicated by results of a dye permeability assay. Preliminary laboratory experiments indicated that temperatures between 35 and 50 degrees C and decreases in soil water potential (-0.003 to -3.20 MPa) increased oocyst inactivation rates. The effects of two common animal waste management practices on oocyst survival were investigated on three dairy farms in Delaware County, N.Y., within the New York City watershed: (i) piling wastes from dairy youngstock (including neonatal calves) and (ii) spreading wastes as a soil amendment on an agricultural field. Sentinel containers filled with air-dried and sieved (2-mm mesh) youngstock waste or field soil were wetted and inoculated with 2 million oocysts in an aqueous suspension and then placed in waste piles on two different farms and in soil within a cropped field on one farm. Controls consisted of purified oocysts in either phosphate-buffered saline or distilled water contained in sealed microcentrifuge tubes. Two microdata loggers recorded the ambient temperature at each field site. Sentinel experiments were conducted during the fall and winter (1996 to 1997) and winter (1998). Sentinel containers and controls were removed at 2- to 4-week intervals, and oocysts were extracted and tested by the dye permeability assay. The proportions of potentially infective oocysts exposed to the soil and waste pile material decreased more rapidly than their counterpart controls exposed to buffer or water, indicating that factors other than temperature affected oocyst inactivation in the waste piles and soil. The effect of soil freeze-thaw cycles was evident in the large proportion of empty sentinel oocysts. The potentially infective sentinel oocysts were reduced to <1% while the proportions in controls did not decrease below 50% potentially infective during the first field experiment. Microscopic observations of empty oocyst fragments indicated that abrasive effects of soil particles were a factor in oocyst inactivation. A similar pattern was observed in a second field experiment at the same site.     

A review of allergic respiratory disease in laboratory animal workers.

There is increased recognition of hypersensitivity lung disease among workers with laboratory animals as an occupational disease. Symptoms of asthma in 44 of 78 workers with laboratory animal dander allergy reflected the serious consequences of this occupational ailment. Affected employee profiles induced family history of atopy; immediate (Type I) allergic reaction; symptoms of rhinitis, asthma, and cough; hypersensitivity to one or more species, most often rats, mice, and rabbits. Diagnosis depends on history and physical, radiologic, and laboratory examinations, including skin tests with relevant antigens. Control and treatment depend on environmental change (reemployment or reduction of antigen contact); mechanical devices (masks and filters); chemotherapy (bronchodilators, steroids), prophylaxis and immunotherapy (hyposensitization). Standardization of medico-legal criteria covering occupational asthma is needed.     

Future directions in small animal imaging

The adaptation and development of imaging technologies for use in small animals has the potential to be a refinement with profound effects on how basic cancer research using animals is conducted. The authors describe how NCI funding is helping to advance research in this area.