William E. Blevins

Gastric retention properties of superporous hydrogel composites

In many applications, usefulness of conventional hydrogels is limited by their slow swelling. To improve the swelling property of the conventional hydrogels, we have synthesized superporous hydrogels (SPHs) which swell fast to equilibrium size in minutes due to water uptake by capillary wetting through numerous interconnected open pores. The swelling ratio was also large in the range of hundreds. The mechanical strength of the highly swollen SPHs was increased by adding a composite material during the synthesis. The composite material used in the synthesis of SPH composites was Ac-Di-Sol((R)) (croscarmellose sodium). The gastric retention property of the prepared SPH composites was tested in dogs both in fasted and fed conditions. The SPH composites were placed in a hard gelatin capsule (size 000) for oral administration. All dogs tested were fasted for 36 h before experiments. Under the fasted condition, the SPH composite remained in the stomach for 2-3 h after before breaking into two pieces and being emptied. When food was given before the experiment just once following 36 h of fasting, the SPH composite remained in the stomach for more than 24 h, even though the fed condition was maintained only for the first few hours. Our study indicated that SPH composites possessed three properties necessary for gastric retention: fast swelling; superswelling; and high mechanical strength. While more improvements need to be made, the SPH composites provide the basis for the development of effective long-term gastric retention devices.

Small Intestinal Submucosa as a Small-Diameter Arterial Graft in the Dog

Autogenous saphenous vein, human umbilical vein, modified bovine collagen, Dacron, and PTFE have been used as small-diameter arterial grafts with moderate success. We tested autogenous small intestine submucosa as a small-diameter arterial graft in both a carotid and femoral artery (mean ID 4.3 mm) of 18 dogs (total of 36 grafts). All dogs received aspirin and warfarin sodium for the first 8 weeks after surgery. Graft patency was evaluated by Doppler ultrasound techniques and angiography. Two grafts ruptured and 5 grafts occluded by 21 days after surgery. One graft became occluded at 14 weeks. Fifteen dogs were sacrificed at periodic intervals until 48 weeks after surgery. Patent grafts had no evidence of infection, propagating thrombus, or intimal hyperplasia. Graft aneurysmal dilation occurred in 4 grafts (11%). The grafts were composed of a dense organized collagenous connective tissue with no evidence of endothelial cell growth on the smooth luminal surface. Three dogs are alive at 76 to 82 weeks after surgery. Overall, graft patency was 75%. Graft patency after cessation of anticoagulation therapy was 92.3% (12 of 13 grafts). We conclude that autogenous small intestinal submucosa can be used as a small-diameter arterial graft in the dog and is worthy of further investigation.

In vitro and in vivo studies of enzyme-digestible hydrogels for oral drug delivery

Abstract Gastric retention of enzyme-digestible hydrogels in dogs was studied to develop a platform for longterm oral drug delivery. The movements of hydrogels in the canine stomach and the gastric tissue-hydrogel interactions were visualized in real-time using three imaging techniques: radiography, fluoroscopy, and 2-D ultrasonography. Hydrogels with appropriate size and integrity were retained in the stomach for more than 24 h even under fasted conditions. Gastric retention was prolonged up to 60 h when the 24 h-fasted state was followed by a once-a-day pelletized meal. In vitro drug release from enzyme-digestible hydrogels was examined. The hydrogels were loaded with flavin mononucleotide (FMN) and air-dried for 7 days. FMN was released from the gels in the simulated gastric juice for up to 454 h and 650 h in the presence and absence of pepsin, respectively. About 90% of the loaded FMN was released in 300 h. During this time, the presence of pepsin in the solution did not make any significant difference in the release profiles. When the FMN-containing hydrogels were administered to dogs, the blood concentration of FMN was maintained at the level of 0.75 μg/ml for 24 h under fasted conditions. In each experiment, the presence of a hydrogel in the stomach was confirmed using the three imaging techniques. When the 24-h-fasted state was followed by a once-a-day meal, appreciable FMN concentration was detected in the blood for up to 54 h. This study showed that once-a-day oral drug delivery is possible even with a drug which is absorbed only from the upper small intestine and has a short half-life.

Inflation of the esophagus and vocal tract filtering in ring doves

SUMMARY Ring doves vocalize with their beaks and nostrils closed, exhaling into inflatable chambers in the head and neck region. The source sound produced at the syrinx contains a fundamental frequency with prominent second and third harmonic overtones, but these harmonics are filtered out of the emitted signal. We show by cineradiography that the upper esophagus, oral and nasal cavities collect the expired air during vocalization and that the inflated esophagus becomes part of the suprasyringeal vocal tract. The level of the second and third harmonics, relative to the fundamental frequency (f0), is reduced in the esophagus and emitted vocalization compared with in the trachea, although these harmonics are still considerably higher in the esophagus than in the emitted signal. When the esophagus is prevented from fully inflating, there is a pronounced increase in the level of higher harmonics in the emitted vocalization. Our data suggest that the trachea and esophagus act in series as acoustically separate compartments attenuating harmonics by different mechanisms. We hypothesize that the trachea behaves as a tube closed at the syringeal end and with a variable, restricted opening at the glottal end that lowers the tracheal first resonance to match the f0 of the coo. The inflated esophagus may function as a Helmholtz resonator in which the elastic walls form the vibrating mass. Such a resonator could support the f0 over a range of inflated volumes.

Use of ultrasound imaging and fluoroscopic imaging to study gastric retention of enzyme-digestible hydrogels

Ultrasound and fluoroscopic imaging techniques were used to monitor the gastric retention of enzyme-digestible hydrogels in the canine stomach. When water was present in the stomach, ultrasound imaging was very effective in monitoring the position of the hydrogel in the stomach, solvent penetration into the gel, and the gastric tissue-gel interactions during peristalsis. Rubbery or fully swollen hydrogels appeared as sonolucent objects with ultrasound imaging. Partially swollen hydrogels displayed a sonolucent outer layer due to solvent penetration and a centrally located bright echo resulting from the acoustic impedance mismatch at the glassy/rubbery interface. The degree of gastric tissue-gel interactions during peristalsis was inversely related to the extent of lumenal distention with water. The effectiveness of peristaltic contractions in driving the hydrogel toward the pyloric sphincter increased as the water was emptied from the stomach. In the absence of water, imaging of the gel with ultrasound became difficult. For this reason, gels were loaded with diatrizoate meglumine/sodium diatrizoate to visualize in real-time using fluoroscopic imaging. Fluoroscopic imaging allowed only indirect assessment of the hydrogel movement during peristalsis and the degree of hydrogel swelling. The gastric retention of the hydrogel under fasted conditions was influenced by the degree of gel deformation in response to peristaltic contractions. Hydrogels with a low degree of deformation during peristalsis showed long gastric retention times. The utilization of ultrasound imaging and fluoroscopic imaging for monitoring dynamic events in the stomach provided information on hydrogel properties which are important to gastric retention. The use of these imaging techniques in the development of long-term oral drug delivery systems is described.

The potential use of poly(methacrylic acid) hydrogels for oral administration of drugs and vaccines to ruminants

Abstract Poly(methacrylic acid) hydrogels were investigated for the delivery of a model antigen to the lower gastrointestinal tract of sheep. Hydrogels were tested by incorporating a radiopaque material, administering them orally to a sheep, and then radiographing the sheep. The potential for loading high molecular weight proteins into hydrogels was determined by absorbing hydrogels with culture supematants of the bacterium Pasteurella haemolytica . The hydrogels were dried, hydrated, and the culture supematants eluted. The eluents were assayed for the presence of the 102 kDa proteinaceous exotoxin. The hydrogels readily bypassed the first stomach and swelled releasing a radiopaque dye into the lower gastrointestinal tract. Chromium-loaded hydrogels were then administered to a sheep and intestinal contents were collected for 5 days. Chromium was detected in the intestinal contents of the sheep for 96 h with peak levels detected at 12–15 h after administration. Eluents of the hydrogels loaded with culture supematants contained readily detectable amounts of the proteinaceous exotoxin. PMA hydrogels were then absorbed with a vaccine consisting of culture supematants of a pulmonary bacterium P. haemolytica . Hydrogels containing vaccine were administered orally to calves. Calves were challenged by an intrabronchial dose of bacteria. The length of time each calf survived was noted. All surviving calves were killed 3 days post-challenge. A post-mortem examination was performed to evaluate the severity of the pneumonic lesions. Vaccinated calves had less pneumonia and lived longer than control calves. Results of this study indicate that poly (methacrylic acid) hydrogels could be used to administer drugs and proteinaceous vaccines orally to ruminants.

Cell-autonomous recognition of the rust pathogen determines rp1-specified resistance in maize.

The Rp1 gene of maize determines resistance to the leaf rust pathogen Puccinia sorghi. X-ray treatment of heterozygous (Rp1 Oy/rp1 oy) maize embryos generated seedlings with yellow sectors lacking. Rp1. Yellow sectored seedlings inoculated with rust spores gave rust pustule formation in yellow (Rp1-lacking) sectors and hypersensitive resistance in green tissues, thereby demonstrating that the Rp1 gene product is cellautonomous in its action. In cases where the hypersensitive reaction was initiated in green (Rp1) tissue next to a yellow sector, the hypersensitive response appeared to be propagated poorly, if at all, through Rp1-lacking cells.

Penile prolapse and urethral obstruction secondary to lymphosarcoma of the penis in a dog

A 5-year-old Chihuahua presented for clinical signs of dysuria and penile prolapse. Radiographic studies identified a urethral obstruction distal to the junction of the proximal and middle third of the os penis that appeared to be secondary to swelling of the penis. Penile resection combined with a scrotal urethrostomy was performed. Histopathological examinations of tissue samples of the body of the penis revealed lymphosarcoma. Lymphosarcoma of the penis is a rare finding in all species. It can occur as a primary tumor of the penis in dogs. Penile lymphosarcoma should be considered in the differential diagnosis of dogs affected with penile prolapse and dysuria.

Syndactyly in a litter of cats

In this case report, we describe the clinical and radiographic features of a litter of kittens affected with complex syndactyly. We also provide guidelines for the diagnosis, possible treatment and prevention of propagation of this condition. This is the first report of syndactyly in a litter of kittens and syndactyly affecting both the pectoral and pelvic limbs.

Bilateral iliopsoas muscle contracture and spinous process impingement in a German Shepherd dog.

OBJECTIVE To report diagnosis and treatment of bilateral iliopsoas muscle contracture in a dog with spinous process impingement. STUDY DESIGN Case report. ANIMALS German Shepherd dog. METHODS A dog with chronic progressive lameness, flexion contracture of the coxofemoral joints, severe pain, and decreased femoral reflexes had severe spondylosis bridging the vertebral bodies from L1 to L4 and enlarged dorsal spinous processes from T8 to L6 with impingement and bony proliferation. Ultrasonographic and magnetic resonance imaging (MRI) findings were consistent with fibrosis, mineralization, and atrophy of the iliopsoas muscles bilaterally which was treated by staged tenectomy of the insertions of the iliopsoas muscles. RESULTS Because of severe perivascular fibrosis, the femoral vessels required ligation. Bilateral iliopsoas muscle tenectomy improved gait and provided pain relief. Histologic findings were consistent with fibrotic myopathy. CONCLUSIONS Slow progression of severe clinical signs observed bilaterally in this dog differs from previous reports of iliopsoas myopathy. Findings were similar to the fibrotic myopathy of the gracilis or semitendinosus muscles described in dogs. CLINICAL RELEVANCE Iliopsoas muscle abnormalities should be considered in dogs with limited hip extension and pain. MRI is useful for diagnosing muscle fibrosis. Iliopsoas tenectomy may improve clinical function in dogs with fibrotic myopathy.