Inhibition of dihydropyrimidine dehydrogenase by 5-propynyluracil, a metabolite of the anti-varicella zoster virus agent netivudine.

OBJECTIVE: To study the effects of the anti-herpetic drug netivudine on dihydropyrimidine dehydrogenase activity in elderly volunteers and to relate them to concentrations of netivudine and its metabolite 5-propynyluracil. METHODS: Three groups of eight elderly volunteers received 400 or 800 mg netivudine or placebo once daily for 8 days. Plasma netivudine, 5-propynyluracil, and uracil, an indirect measure of dihydropyrimidine dehydrogenase activity, were assayed before the first dose and on days 2, 3, 5, 7 and 8. Full plasma profiles of netivudine and 5-propynyluracil were determined after the last dose. RESULTS: Plasma uracil was unquantifiable in all subjects before the first dose and at all time points in the placebo group. In recipients of netivudine it reached a plateau between days 3 and 5, with mean values of 23.2 and 23.5 mumol/L on day 8 in the subjects who received 400 and 800 mg. Plasma netivudine concentrations were approximately dose proportional, but 5-propynyluracil concentrations were similar in both groups. The half-maximal rise in plasma uracil occurred after a cumulative 5-propynyluracil exposure of 120 mumol/L.hr; such exposures will be achieved even after doses as low as 50 to 100 mg daily. CONCLUSIONS: Netivudine dosing produces complete inhibition of plasma dihydropyrimidine dehydrogenase. Coadministration with the antimetabolite 5-fluorouracil will require a substantial reduction in 5-fluorouracil dose to avoid toxicity but may also improve the therapeutic index of 5-fluorouracil.

Feline immunodeficiency virus model to study human immunodeficiency virus/acquired immune deficiency syndrome conditions.

This study was designed to induce rapid progression of the feline immunodeficiency virus (FIV) infection in cats. Predictably inducing the FIV disease state in the cat would yield an excellent tool to study endodontic disease processes under immunosuppressed conditions. Eight cats were immunosuppressed with steroids before infection with FIV. Another eight cats, age- and sex-matched littermates, served as uninoculated seronegative controls. Complete blood counts were taken for 10 mo in the FIV group, and 10 wk in the control group, including lymphocyte subsets. ELISAs were used to detect FIV infection. Statistical analysis was performed with generalized estimating equation models. All cats were positive at one point in time. The FIV group had significantly lower peripheral blood CD4+ counts compared with the control group. Therefore the FIV model presented gives the desired outcome and simulates what occurs in human immunodeficiency virus infection.

Oral and periodontal tissue. Maintenance, augmentation, rejuvenation, and regeneration.

This article discusses the controversies, usefulness, and limitations of oral and periodontal tissue maintenance, augmentation, rejuvenation, and regeneration in the dog and cat. It details many of the specialized materials and techniques used in these procedures in attempts to re-establish healthy conditions within the periodontium. Bone loss following tooth extraction is discussed with consideration as to which teeth should have alveolar ridge maintenance procedures and the important reasons as to why. Radiographs show the degree of improvement demonstrated in treatment of various cases involving bone loss from periodontal disease, treatment of bone injuries with oral fractures and their prevention.

Dental diseases of puppies and kittens.

Although there are certain differences warranting specific options therapeutically in young animals, many of the basic dental principles still apply. The key is examining the oral cavity of every patient at each visit and knowing how to recognize and manage any abnormalities encountered. Providing sound oral care from the time of a patient's first visit can figure significantly in a lifelong commitment to oral health that can have a positive impact on the patient's overall health.

An alternative hypothesis from veterinary science for the pathogenesis of noncarious cervical lesions.

An alternative hypothesis to abrasion and erosion for the pathogenesis of noncarious cervical lesions was put forward in 1984; the so-called occlusal theory suggested that tensile stresses from occlusal overload could be involved in the pathogenesis of noncarious cervical lesions and that bending stresses applied to teeth could cause disruption of the surface enamel, resulting in increased susceptibility to dissolution and abrasion at the affected sites and in the development of wedge-shaped lesions. This theory has gained increased acceptance in recent years, although absolute scientific evidence has been scant. These lesions also occur in animals, in particular, the domestic cat, in which they are called feline odontoclastic resorptive lesions. A variety of theories about pathogenesis of these lesions have been put forward, but there is some evidence that occlusal overload may be a contributory factor in the development of an inflammatory response in the periodontal membrane and the presence of enzymes associated with resorption in the gingival crevice. Further investigation may help define a common etiology between the pathogenesis of feline odontoclastic resorptive lesions and noncarious cervical lesions.

Endodontic instrumentation.

Endodontic instruments are used within the tooth pulp chamber and root canal systems. An understanding of the armamentarium of endodontic instrumentation is necessary in the selection of, and proper use of, these instruments. This proper selection and use of instruments along with the meticulous use of the endodontic triad, can greatly increase the probability of success of endodontic procedures. The endodontic triad is canal preparation, sterilization, and obturation. The object of preparation is to prepare the canal to accept obturation with a positive seal and appropriate sealer. This article describes in detail, the types of endodontic instrumentation available.

Anatomy, diagnosis and management of disorders of the tongue.

The tongue is an integral and functional part of the oral cavity. This article reviews and describes various disorders of the tongue. A comprehensive description of diagnosis and management of tongue problems is included. A review of the anatomy related to the tongue is described.

Dental and oral disease in Lagomorphs.

The dental diseases of rabbits are unique because of their dental anatomy and physiology. Common problems of Lagomorph dentition are covered in this article including malocclusions, periodontal disease, and their treatment. The anatomy of Lagomorph dentition is reviewed and anesthesia protocols are included.

Acute and chronic alveolitis/osteomyelitis ("lumpy jaw") in small exotic ruminants.

Tooth-related abscesses in small captive ruminants are most likely foreign body-induced periodontic-endodontic lesions. The instigating cause may be abnormal texture of dietary material. Bacteria, though probably not the initiating cause, significantly contribute to pathology and morbidity. Extraction of severely affected teeth is an effective although sometimes challenging mode of treatment. Periodically complications may arise, which vary in difficulty of treatment. Prevention may be the alteration of the major forage component of the diet to textures that are less coarse and stemmy, and the alleviation of any crowding and sanitation problems.

Dentigerous cyst in a dog.

An infrequently occurring tumor-like lesion arising from the cellular components of the developing dental follicle is the dentigerous cyst. These odontogenic cysts have classic clinical and radiographic findings. The cysts are locally invasive and aggressive and require prompt surgical management. This case describes the diagnosis and surgical treatment of a dentigerous cyst in the mandible of a dog.

Modified surgical treatment of intermittent open-mouth mandibular locking in a cat.

Intermittent open-mouth locking related to disorders of the temporomandibular joint are not uncommon. As a result of joint laxity, the mandible shifts to one side. The coronoid process then becomes locked lateral to the zygomatic arch. These patients present with the mouth opened and an inability to close the mouth. This article describes a case of intermittent open-mouth mandibular locking in a cat and a modified surgical treatment combining zygomatic arch and coronoid process reduction.

Veterinary dental demonstration models.

This article is about dental models and their construction. It is meant to be informative, entertaining and, hopefully, a little lighthearted. The use of dental models in the veterinary practice has become commonplace. The models are useful for demonstrating to clients and colleagues various dental pathologies and procedures.

The chairside developer and the making of an inexpensive unit.

A chairside developer using rapid developer/fixer solutions is an indispensible aid for the veterinary dental practitioner. These units can be expensive. This "light-hearted cowboy" article describes how to construct a chairside dental film developer using inexpensive materials.

Are we going round in circles, or standing still (and did the Cheshire cat smile enigmatically because of resorptive lesions)?

April 1, 1995. Recent advances and directions in veterinary dentistry are reviewed, to point out that not a lot of progress is being made on some fronts, and none at all on others. The authors conclude that veterinary dentists should brush their own and their pets' teeth at least once during their professional careers.

Clinical evaluation of SofScale Calculus Scaling Gel in dogs and cats.

An in-depth study was performed using SofScale Calculus Scaling Gel to determine its value in assisting animal dental prophylaxis as compared to nontreated teeth. A total of one hundred and five animals (dogs and cats) were tested. This gel saved a slight amount of time on animal full mouth prophylaxis in many cases, especially in heavy calculus groups. The gel helped to reduce total actual scaling time, but did not reduce actual procedure time.

Microglossia in three littermate puppies.

Three of five two-day-old Miniature Schnauzer puppies were diagnosed as having 'bird-tongue,' a microglossia that prevents normal nursing. With intensive nursing care, the puppies survived to seven weeks of age, then deteriorated and were euthanized. From clinical and pathological examinations, a multi-system defect is suspected, though no primary neuromuscular abnormality could be determined.

Effects of preactivated MC540 in the treatment of lymphocytic plasmacytic stomatitis in feline leukemia virus and feline immunodeficiency virus positive cats.

Photoactive compounds and drugs are used therapeutically as antibacterial, antiviral and antitumor agents. This report examines the use of a photoactive compound, preactivated merocyanine 540 (pMC540), in the treatment of stomatitis in two cats that are both feline immunodeficiency virus (FIV) positive. One of the cats was also feline leukemia virus (FeLV) positive. Dramatic short term improvement is reported with the dosage regimen and complications.

Comparison of two heated gutta percha and sealer obturation techniques in canine teeth of dogs.

The overall endodontic fill and apical seal achieved using two different obturation methods were compared. Twenty-six adult dog canine teeth were instrumented and obturated using either a warm vertical or heated lateral technique. Zinc oxide-eugenol sealer was applied by paper point in the warm vertical technique and by syringe injection in the heated lateral technique. The cadaver jaws were warmed to 35-37 degrees C (95-98.6 degrees F) during obturation using a circulating warm water bath. Obturation times were recorded and ventrodorsal, lateral, and oblique dental radiographs were taken of all teeth for comparison. Twenty-two of the canine teeth were extracted and an apical dye study was performed using a clearing technique. Apical dye leakage was linearly measured to evaluate the furthest ink penetration into the root canal. Although radiographically the heated lateral method appeared to have a better endodontic fill, there was significantly greater apical dye leakage in teeth obturated with that combination of sealer and gutta percha. There was also extrusion of sealer and root fracture associated with the heated lateral technique. The method of sealer application was different for each technique; this variable should be taken into consideration when interpreting our results, which suggest that the warm vertical compaction technique may provide a better apical seal in canine teeth of dogs in a shorter period of time, with fewer obturation complications when compared to the heated lateral technique.