Irmeli Happonen

Comparison of diagnostic methods for detecting gastric Helicobacter-like organisms in dogs and cats.

Diagnostic methods for detecting gastric Helicobacter-like organisms (GHLOs) in dogs and cats were compared. Samples for brush cytology, the urease test and histological examination were collected post mortem from the fundus, corpus and antrum of 10 dogs (17 sample sites from each animal) and 10 cats (14 sample sites each). Samples of tissue from the fundus or corpus were taken for transmission electron microscopy and culture from three and eight dogs, respectively, and from six cats that gave a positive urease test with samples from these regions. In all dogs and in six of the 10 cats, GHLOs were detected by at least one of three methods (brush cytology, urease test or histological examination) in all regions. By brush cytology, GHLOs were demonstrated in all samples from the dogs and the positive cats. In cats, the urease test (60 min) gave a positive result in every sample site; in dogs it gave a positive result in 100% of the corpus samples, in 95% of the fundus samples and in 62% of the antral samples. Histological examination revealed GHLOs in all samples from the fundus and corpus of the dogs and of the positive cats; and in 74% and 91.7% of the antral samples of the dogs and cats, respectively. GHLOs were seen in all dogs and cats studied by transmission electron microscopy, and culture of gastric tissue was successful in 3/8 dogs and 1/6 cats. In this study, brush cytology was thus the most sensitive method for demonstrating GHLOs.

Transmission of canine gastric Helicobacter salomonis infection from dam to offspring and between puppies

H. bizzozeronii CCUG 35045, a new canine gastric Helicobacter spp. was used for experimental infection of four weaned puppies at 7 weeks of age. Controls were four nonchallenged puppies. The puppies originated from two dams which had Helicobacter salomonis infection in biopsy samples taken 3 weeks before the delivery but which had urease, brush cytology and culture-negative biopsy samples taken 7 weeks after antimicrobial treatment (metronidazole, amoxicillin, bismuth subcitrate). Both dams were detected urease- and Helicobacter-positive again three and a half months after therapy. Dam B was shown to be colonised with the similar genotype of H. salomonis for more than 2 years. Unexpectedly, H. salomonis was also cultured from gastric biopsy samples of the nonchallenged puppies three times during 7 months. When H. salomonis isolates of dams and puppies were studied by ribotyping (HaeIII, ClaI or PstI) they were shown to be identical although the HaeIII and PstI REA patterns of dam A differed from the patterns of dam B and nonchallenged group by one fragment. PFGE pattern analysis of NotI digests, however, revealed that the isolates of the puppies were identical with the isolates of dam B, and differed from the isolates of dam A. The isolates of the dams and puppies in the nonchallenged group were metronidazole-resistant. The antimicrobial therapy had merely suppressed, but not eradicated, the infection from dams. These studies suggested that puppies may acquire gastric Helicobacter infection from dams during the lactation period and puppies can infect each other during their early life. PFGE pattern analysis was shown to be a more distinguishing method than ribotyping to study the similarity of the isolates.

The fate of multiple-unit enteric-coated formulations in the stomach of the dog

Abstract The gastrointestinal transit of enteric granules was studied in healthy dogs and in a dog suffering from pancreatic insufficiency by means of roentgenography. Coated granules of different sizes were given to the dogs during the main meal or with a small portion of food before the meal. The enteric materials used were hydroxypropyl methylcellulose phthalate (HPMCP) and cellulose acetate phthalate (CAP). The majority of enteric granules with a diameter of 0.3–1 mm and 1–1.7 mm remained in the stomach for up to 6–8 h. Reduction in granule size and the time of adding the drug to the food were shown to have no significant effect on the gastric emptying of these granules. The formulations were emptied from the stomach much later than food, and it is therefore highly questionable whether this particular dosage form is suitable for the treatment of pancreatic insufficiency in dogs. A special type of controlled-release granule was developed, using HPMCP as a coat (7%) and potato starch as a disintegrant in the core. This formulation disintegrated in front of the pylorus 1–2 h after drug administration, showing an almost ideal release of the drug suitable e.g. for pancreatic enzyme therapy. However, further development is necessary.

Formulations releasing the drug proximal to the pylorus in the dog

Abstract To overcome various difficulties associated with the replacement of drug therapy for pancreatic insufficiency, film-coated tablets releasing the drug in front of the pylorus were developed and studied in dogs using a series of X-rays. The tablets, containing pregelatinized starch or carmellose as a disintegrant, were coated with cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose phthalate (HPMCP) or methacrylic acid co-polymer (Eudragit L) combined with the soluble polymers, hydroxypropyl methylcellulose (HPMC) or methacrylate esters co-polymer (Eudragit E). Sustained-release tablets were coated with ethyl cellulose (EC) containing small amounts of HPMC. When administered with food, controlled drug release was achieved in front of the pylorus with conventional enteric materials if the tablets also contained a suitable disintegrant. EC-HPMC-coated tablets act as a prolonged action formulation, releasing the drug for up to 5–7 h in front of the pylorus and thereafter in the intestine. As demonstrated in these dog studies, it should therefore be possible to develop sustained-release formulations which release pancreatic enzymes for a prolonged period of time in a site favourable for their digestive function.

Disintegration of hard gelatin capsule formulations in the dog stomach — a radiological study

Abstract The final decision as to the suitable composition of an oral drug formulation should be made on the basis of in vivo studies. A radiological technique was developed for studying the in vivo disintegration of hard gelatin capsules in the stomach of the dog. Highly water-soluble additives such as sucrose and lactose caused rapid disintegration (10–15 min). Formulations containing semisolid material disintegrated in roughly 20 min. The mean disintegration time for capsules containing microcrystalline cellulose or dicalcium phosphate dihydrate was 37 min and 44 min, respectively. Capsules containing corn starch or carboxymethylcellulose sodium disintegrated very slowly and clearly adhered to the gastric mucosa. Very rapid disintegration (mean 9 min) was observed with capsules containing small coated pellets, which indicates that hard gelatin capsules may be a good dosage form for multiparticular modified-release formulations. The correlation between in vitro and in vivo data was unsatisfactory.