Long-term exposure of human proximal tubule cells to hydroxycobalamin[c-lactam] as a possible model to study renal disease in methylmalonic acidurias.

Dysfunction of proximal tubules resulting in tubulointerstitial nephritis and chronic renal failure is a frequent long-term complication of methylmalonic acidurias. However, the underlying pathomechanisms have not yet been extensively studied owing to the lack of suitable in vitro and in vivo models. Application of hydroxycobalamin[c-lactam] has been shown to inhibit the metabolism of hydroxycobalamin and, thereby, to induce methylmalonic aciduria in rats, oligodendrocytes, and rat hepatocytes. Our study characterizes the biochemical and bioenergetic effects of long-term exposure of human proximal tubule cells to hydroxycobalamin[c-lactam], aiming to establish a novel in vitro model for the renal pathogenesis of methylmalonic acidurias. Incubation of human proximal tubule cells with hydroxycobalamin[c-lactam] and propionic acid resulted in a strong, time-dependent intra- and extracellular accumulation of methylmalonic acid. Bioenergetic studies of respiratory chain enzyme complexes revealed an increase of complex II-IV activity after 2 weeks and an increase of complex I and IV activity as well as a decrease of complex II and III activity after 3 weeks of incubation. In addition, human proximal tubule cells displayed reduced glutathione content after the exposure to hydroxycobalamin[c-lactam] and propionic acid.

Oral health status of adults from a California regional center for developmental disabilities.

The oral health status and treatment needs of developmentally disabled adults (18 years and older) from a Los Angeles Regional Center who live in a variety of settings were measured as part of a comprehensive study to determine their overall health status. A dental assessment was performed on a sample of 325 persons which was similar in demographic composition to the entire population at the center. Approximately 80% of clients reported a personal dentist of record, and 73% brushed their own teeth. Edentulism was 9%. The mean number of retained teeth per person was 22. Subjectively, 15.7% of the sample was rated as having "good" overall dental health, 77.7% "fair," and 6.6% "poor." The major reasons rendering fair or poor assessments were oral hygiene, clinical periodontal disease, and dental caries. More females than males were assessed as having "good" overall dental health. The overall appearance of the teeth for a majority of the sample (76.5%) was rated as "same as most." Persons who brushed their own teeth had fewer missing teeth than those who did not. Persons with a dentist of record had fewer decayed and more filled teeth. Persons living at home with family or friends had a significantly lower DMFT index than those living independently or in facilities. In general, these findings are encouraging; however, caution must be exercised, since efforts to improve the oral health status of this population require continued attention.

Host fidelity is an effective premating barrier between sympatric races of the apple maggot fly.

Models of sympatric speciation for phytophagous insects posit a central role for host plant-associated mating as a premating isolating mechanism in lieu of geographic barriers to gene flow. Here, by means of three mark-and-recapture studies, we confirm that host fidelity (i.e., the tendency of an insect to reproduce on the same host species that it used in earlier life-history stages) restricts gene flow between sympatric apple- and hawthorn-infesting races of Rhagoletis pomonella (Diptera: Tephritidae) to approximately 6% per generation. Genetically based differences in host preference, adult eclosion under the "correct" host species, and allochronic isolation contribute to host fidelity in various degrees in the races. The results verify that host-associated adaptation can produce reproductive isolation as a correlated character (a key premise of sympatric speciation). The study also represents one of the few or perhaps only example in animals where the intra-specific isolating effects of specific phenotypes have been quantified in nature.