Autoregulation of periodontal ligament cell phenotype and functions by transforming growth factor-beta1.

During orthodontic tooth movement, mechanical forces acting on periodontal ligament (PDL) cells induce the synthesis of mediators which alter the growth, differentiation, and secretory functions of cells of the PDL. Since the cells of the PDL represent a heterogeneous population, we examined mechanically stress-induced cytokine profiles in three separate clones of human osteoblast-like PDL cells. Of the four pro-inflammatory cytokines investigated, only IL-6 and TGF-beta1 were up-regulated in response to mechanical stress. However, the expression of other pro-inflammatory cytokines such as IL-1 beta, TNF-alpha, or IL-8 was not observed. To understand the consequences of the increase in TGF-beta1 expression following mechanical stress, we examined the effect of TGF-beta1 on PDL cell phenotype and functions. TGF-beta1 was mitogenic to PDL cells at concentrations between 0.4 and 10 ng/mL. Furthermore, TGF-beta1 down-regulated the osteoblast-like phenotype of PDL cells, i.e., alkaline phosphatase activity, calcium phosphate nodule formation, expression of osteocalcin, and TGF-beta1, in a dose-dependent manner. Although initially TGF-beta1 induced expression of type I collagen mRNA, prolonged exposure to TGF-beta1 down-regulated the ability of PDL cells to express type I collagen mRNA. Our results further show that, within 4 hrs, exogenously applied TGF-beta1 down-regulated IL-6 expression in a dose-dependent manner, and this inhibition was sustained over a six-day period. In summary, the data suggest that mechanically stress-induced TGF-beta1 expression may be a physiological mechanism to induce mitogenesis in PDL cells while down-regulating its osteoblast-like features and simultaneously reducing the IL-6-induced bone resorption.

Ontogeny of the phagocytic and bactericidal activities of turkey heterophils and their potentiation by Salmonella enteritidis-immune lymphokines.

Heterophils, the functional equivalent to the mammalian neutrophil, are important mediators of natural resistance against invasive pathogens in poultry. Young poultry are susceptible to pathogens, such as Salmonella enteritidis, during the first week post-hatch. No studies have evaluated the ontogeny of heterophil function in turkeys during the first few weeks post-hatch. Previous studies from our laboratory have shown day-old poults were protected against S. enteritidis organ invasion following immunoprophylactic administration of chicken S. enteritidis immune lymphokines. Therefore, the objective in the present study was to characterize the development of phagocytosis and bacterial killing by turkey heterophils during the first 3 weeks of life and to compare the effect of immune lymphokines on the development of heterophil phagocytosis and killing during the first 3 weeks post-hatch. Both functional phagocytosis and killing activities were age-dependent events. During the first 1-7 days post-hatch, little functional activity was demonstrated which apparently is associated with susceptibility. Optimal heterophil phagocytosis and killing activities were reached 14-21 days post-hatch. Administration immune lymphokines significantly potentiated phagocytosis (P < 0.01) and killing (P < 0.001) by turkey heterophils. In fact, immune lymphokine administration to 1-7-day-old poults augmented phagocytosis and killing activities of heterophils equivalent to levels found in functionally mature 14-21-day-old poults. These results demonstrate the ontogeny of the functional activity of the turkey heterophil is an age-related phenomenon, with inefficient phagocytosis and killing during the first week post-hatch. Prophylactic administration of immune lymphokines significantly potentiated the functional activity of the heterophil poults during the first 3 weeks of life. Most importantly the administration of immune lymphokines enhanced the functional activity of heterophils from 1-7-day-old poults to levels comparable to that of an immunologically mature bird.

Adverse effects of fenfluramine in treatment refractory schizophrenia.

Fenfluramine was administered to eight severely ill schizophrenic patients as an adjunct to neuroleptic drugs in a double-blind, multiple baseline design. A significant adverse effect of fenfluramine on psychopathology was detected through nurses' ratings, target symptom scales, the Brief Psychiatric Rating Scale, and time-sampled behavioral observations. Clinical deterioration was correlated with fenfluramine-induced reductions in blood serotonin levels and persisted beyond the point of discontinuation of fenfluramine.

Pharmacotherapeutics in urgent dental care.

A frequent requisite to urgent dental care is the use of pharmacotherapeutic agents as part of the treatment protocol. Anxiolytics, anesthetics, analgesics, and antibiotics are prescribed as dictated by particular clinical situations.