Cyclic AMP phosphodiesterase activity in human gingival carcinoma

BACKGROUND: The phosphodiesterases (PDEs) are responsible for the hydrolysis of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), to their corresponding monophosphates with a fundamental role in the transduction of the intracellular signals. At least 11 different enzymatic isoforms have been identified, which are listed according to their specificity or affinity for the substratum, identity of the amino acid sequence, cofactor, and inhibitor sensitivity. Variations in PDE activity have been found in different pathologies, and they have also been correlated to different pathological e/o physiological mechanisms, such as cellular differentiation, apoptosis, and tumor invasivity. OBJECTIVES: In this study, we have evaluated cAMP PDE activity in patients with carcinoma of the gingiva, with the purpose of correlating differences in its development and progression. The same enzymatic activity has been used to evaluate differences between patients with lymph node involvement (group N(+)), and patients without lymph node involvement (N(-)). MATERIALS AND METHODS: The analysis of PDE activity and the cAMP assay was performed by reverse-phase HPLC on samples of fresh or frozen gingival tissues. Analysis of cAMP was confirmed with the enzyme-linked immunoabsorption assay (EIA). RESULTS AND CONCLUSIONS: The differences between control and N(-) groups (P = 0.0433), and between control and N(+) groups (P = 0.0156) were statistically significant. PDE3A was also evaluated immunohistochemically in lymph-node negative and lymph-node positive cases. The differences between the two groups were statistically significant (P = 0.0397).     

Transverse skeletal base adaptations with bionator therapy: A pilot implant study

The purpose of this randomized, controlled trial was to evaluate transverse skeletal base adaptations to Bionator therapy. The sample included 25 patients (15 male, 10 female) aged 6.9 to 11.2 years with Class II Division 1 malocclusion. The patients were randomly allocated to either a control (n = 11) or treatment (n = 14) group and followed longitudinally for approximately 12 months. Treatment consisted of a Bionator only, constructed to remain approximately 2 mm from the buccal dentition. Transverse maxillary and mandibular changes were evaluated cephalometrically according to 4 bilateral maxillary and 2 bilateral mandibular implants. Untreated Class II controls exhibited significant increases between posterior maxillary implants but no significant changes between the anterior maxillary or mandibular implants. There were no significant width differences between the control and treated groups before treatment. Posterior maxillary implant widths increased significantly (P < .05) in both groups, but the treated group showed significantly greater width increases than the control group. The treated group also showed greater increases between mandibular implants, but the differences were not statistically significant. These results suggest that transverse skeletal base adaptations occur as a result of Bionator therapy.     

Association of the germline BRCA2 missense variation Glu2663Lys with high sensitivity to trabectedin-based treatment in soft tissue sarcoma

We report an interesting clinical case of a patient carrying a specific BRCA2 germline variant affected by bone and hepatic metastases from a high grade uterine stromal sarcoma who obtained a complete metabolic response after only 3 cycles of trabectedin treatment (1.5 mg/m² given intravenously over 24 hours every 21 days). Molecular investigations linked this outstanding positive pharmacological response with the loss of heterozygosity (LOH) of the mutated BRCA2 gene. These data support the hypothesis that the response to trabectedin may be positively conditioned by the different DNA repair defects present in the neoplasm and that BRCAness tumor genotype is important in determining the efficacy of trabectedin-based chemotherapy.     

Anti-Toxoplasma gondii immunoglobulins A and G in human saliva and serum

Paired human saliva and serum samples from 60 individuals were tested for specific IgA and IgG antibodies to Toxoplasma gondii . The study in both fluids was carried out by indirect immunoenzymatic assay (ELISA). Saline antigenic extract of T. gondii was used to coat plastic surfaces upon which the samples were then incubated: monospecific conjugates of anti-IgA and anti-IgG-peroxidase were then incubated with the samples after a washing procedure to separate the unbound antibodies. The enzymatic activity was measured and the results expressed in terms of ELISA index. Toxoplasma -specific IgG antibodies were detected in 43 of the serum samples (7l.7%) and in 12 of the saliva samples (20.0%) whereas Toxoplasma -specific IgA antibodies were detected in 18 of the serum samples (30.0%) and in 12 of the saliva samples (20.0%). No association was observed when the Toxoplasma -specific IgG reactive and non-reactive serum samples were compared with the reactive and non-reactive saliva samples for this class of immunoglobulin. On the other hand, a significant association was observed when the Toxoplasma -specific IgA reactive and non-reactive serum samples were compared with the reactive and non-reactive saliva for this type of antibody. In conclusion, our results show that the detection of salivary IgA reflects the serum level of this isotype but salivary IgG does not. Moreover, the isolated detection of salivary IgG may not contribute to epidemiological studies of chronic toxoplasmic infections.     

Genetic profiling of granular cell myoblastoma

Granular cell tumor (GCT), or granular cell myoblastoma, is a relatively uncommon lesion of the soft tissues. It can occur in any organ, and the tongue is more often affected. GCT has unknown etiology, uncertain histogenesis, and a not always benign nature. Benign myoblastomas are the great majority, but rare malignant lesions have been reported. To have more information regarding the genetic events involved in GCT, the authors decided to perform an expression profile. A sample was derived from a surgically resected GCT of the tongue. RNA extracted from normal tongue (mucosa plus muscle) was used as control. By using DNA microarrays containing 19,200 genes, the authors identified several genes for which expression was significantly up- or down-regulated. The differentially expressed genes cover a broad range of functional activities: (1) signal transduction, (2) cell cycle regulation, and (3) cytoskeleton organization. It was also possible to detect some genes whose function is unknown. The data reported are, to the authors' knowledge, the first genetic portrait of GCT. Mutations in some of the described genes are related to neural alterations and mental diseases, and this fact supports the idea of a neural origin of myoblastoma. Several markers have been identified that will help in identifying the biological behavior (when malignant lesions will be described), as well as the gene whose products could be potentially disease-specific targets for therapy.     

Zirconium implant abutments: fracture strength and influence of cyclic loading on retaining-screw loosening.

OBJECTIVE: The purpose of this study was to determine the fracture strength of zirconium implant abutments and the torque required to unfasten the retaining screw before and after applying cyclic loading to the implant-abutment assembly. The dynamic behavior and stress distribution pattern of zirconium abutments were also evaluated. METHODS AND MATERIALS: Static and cyclic loading of 7 XiVE implants with straight Cercon zirconium abutments were simulated under worst-case conditions. Cyclic loading tests were performed via a servohydraulic dynamic testing machine at loads between 100 and 450 N, for up to 5 million loading cycles, at 15 Hz. The dynamic behavior of the zirconium abutments was analyzed by finite element modeling and Pro/Mechanica software, comparing van-der-Mises and maximum stress levels. RESULTS: Cercon zirconium-ceramic abutments exhibited a maximum fracture strength of 672 N during static loading and 269 N at 800,000 to 5 million cycles runout point, and 403 N at 10,000 cycles runout point during cyclic loading. The mean torque value required to unfasten the abutment retaining screws after (initial) tightening was 21 Ncm +/- 1 and 20 Ncm +/- 1 (measurement accuracy +/- 2 Ncm) after loading with up to 5 million cycles respectively. Torque values decreased minimally and screw loosening did not occur. Within the limited number of test specimens (7), the difference was statistically significant (P = .015). FEM analysis displayed higher stress peaks up to 800 MPa at the cervical aspect of the zirconium abutment and at the apical third of its retaining screw at an external load of 250 N. CONCLUSION: Within the limitations of this study, zirconium implant abutments exceeded the established values for maximum incisal bite forces reported in the literature and tightly fit into the titanium implant after several millions of loading cycles.     

Alveolar ridge augmentation: a comparative longitudinal study between calvaria and iliac crest bone grafrs

Insertion of endosseous implants is often difficult because of lack of supporting bone. In the case of severe atrophy of the jaws, a large volume of autogenous bone can be harvested from the iliac crest and calvaria. Both grafts undergo partial resorption with time, but the rate of bone loss has not been fully elucidated. The aim of this study was to evaluate the alveolar bone height gain (ABHG) obtained with iliac crest and calvaria bone grafts. Twenty-five patients had mandibular bone grafts, 32 had maxillary bone grafts, and 11 had both mandibular and maxillary bone grafts. Measures were made on preoperative, postoperative, and follow-up radiographs. A general linear model was used to evaluate the rate of ABHG plotted against months elapsed from the time of the operation to the time of follow-up. General linear model output showed a statistically significant effect for only the type of donor bone graft (P =.004), with a better ABHG for calvaria. The iliac crest bone grafts lost most of the ABHG in the first 6 months, whereas calvaria bone grafts lost ABHG over a greater interval of time. The type of bone graft is the strongest predictor of ABHG, and calvaria bone graft had a higher stability than did iliac bone graft. However, the gap in ABHG between the 2 grafts tended to decrease over time.     

Fetal-maternal HLA-A and -B discordance is associated with placental RNase expression and anti-HIV-1 activity

The incidence of maternal-to-fetal human immunodeficiency virus type 1 (HIV-1) transmission is 25-30% in absence of antiretroviral therapy, and is inversely associated with Human leukocyte antigens (HLA) class-I discordance. Based on our earlier report that mixed lymphocyte reactions (MLR) induce a ribonuclease (RNase) that inhibits HIV-1 replication, we proposed that maternal-fetal alloantigen stimulation activates factors that protect the fetus against vertically-transmitted infections. We investigate here whether the degree of mother-infant HLA discordance associates with the ability to produce anti-HIV-1 alloantigen-stimulated factor (ASF), and affects placental RNases. We also determine whether such HLA association is influenced by the mother's HIV-1 status. Paired maternal and cord blood leukocytes were tested for the induction of ASF by MLR, and typed for HLA-A and -B. The placentas were tested for mRNA expression of three RNases. Neonate anti-mother, but not mother anti-neonate MLR generated supernatants with anti-HIV-1 activity, that was associated with HLA class I discordance. This HLA association was not seen in the HIV-infected cohort. HLA class I discordance was also associated with expression of placental RNase 1. Our findings are consistent with the hypothesis that HLA class I discordance induces expression of RNases in the placenta that contribute to innate host resistance to HIV-1 and other viral infections.