The competition between enamel and dentin adhesion within a cavity: An in vitro evaluation of class V restorations

To gain more insight into the consequences of curing contraction within the tooth cavity, we assessed the margin behavior of 12 contemporary restorative systems in class V restorations with margins located on enamel and dentin after mechanical loading and water storage. Mixed class V cavities were prepared on extracted human molars and restored using five etch and rinse and seven self-etch adhesive systems with their corresponding composites. Marginal adaptation was evaluated by using a computer-assisted quantitative marginal analysis in a scanning electron microscope (SEM) on epoxy replicas before, after thermal and mechanical stressing and after 1 year of water storage. The interactions of "testing conditions", "adhesive-composite combination" and "tooth substrate" with "marginal adaptation" were evaluated by two-way ANOVA. Fatigue, stress and storage conditions had significant effects on the marginal adaptation. Only two groups (Optibond FL and G Bond) presented equal percentages of marginal adaptation on enamel and dentin; in the other groups, the rate of degradation was product dependent. All materials tested showed a distinct behavior on enamel and dentin. In addition to mechanical resistance and long-term stability, differences within materials also exist in their ability to simultaneously bond to enamel and dentin.     

Limitations of IL-2 and Rapamycin in Immunotherapy of Type 1 Diabetes

Administration of low-dose interleukin-2 (IL-2) alone or combined with rapamycin (RAPA) prevents hyperglycemia in NOD mice. Also, low-dose IL-2 cures recent-onset type 1 diabetes (T1D) in NOD mice, partially by boosting pancreatic regulatory T cells (T_reg cells). These approaches are currently being evaluated in humans. Our objective was to study the effect of higher IL-2 doses (250,000–500,000 IU daily) as well as low-dose IL-2 (25,000 IU daily) and RAPA (1 mg/kg daily) (RAPA/IL-2) combination. We show that, despite further boosting of T_reg cells, high doses of IL-2 rapidly precipitated T1D in prediabetic female and male mice and increased myeloid cells in the pancreas. Also, we observed that RAPA counteracted IL-2 effects on T_reg cells, failed to control IL-2–boosted NK cells, and broke IL-2–induced tolerance in a reversible way. Notably, the RAPA/IL-2 combination failure to cure T1D was associated with an unexpected deleterious effect on glucose homeostasis at multiple levels, including β-cell division, glucose tolerance, and liver glucose metabolism. Our data help to understand the therapeutic limitations of IL-2 alone or RAPA/IL-2 combination and could lead to the design of improved therapies for T1D.In type 1 diabetes (T1D), the immune system destroys the pancreatic β-cells (1). At clinical onset, ∼30% of β-cells are still able to produce insulin (2), thus stopping autoimmune destruction, which at this stage is a promising approach (3). Along the same lines, there is a growing list of phase I/II clinical trials based on immunomodulation that are currently being conducted in T1D patients (4).NOD mice, which develop spontaneous T1D, represent an accepted model for testing new therapies (5), the gold standard being that treatments that cure overt hyperglycemia in these mice may be most appropriate for translation into the clinic, as was the case for anti-CD3 antibodies (Abs) (6), which have been tested in patients with promising results (7). In addition, results from our own group showing that low-dose interleukin-2 (IL-2) can prevent (8) and revert disease in NOD mice (9) have led to the translation of this strategy into clinical trials in T1D patients (clinical trial reg. no. {"type":"clinical-trial","attrs":{"text":"NCT01353833","term_id":"NCT01353833"}}NCT01353833, clinicaltrials.gov).We have shown that in NOD mice, administration of low-dose IL-2 for 5 days induced the remission of new-onset T1D by specifically boosting regulatory T cells (T_reg cells) in the pancreas without activating pathogenic effector T cells (T_eff cells). However, remission was obtained in only 60% of treated mice, and half of them became diabetic again during the following months (9). Consequently, improving IL-2 therapy by optimizing dosing or combining IL-2 with other immunomodulatory drugs, such as rapamycin (RAPA), could be of great importance for the goal of translating this therapy to humans.RAPA has been used in clinical transplantation for many years (10), and it has been safely administered to T1D patients during islet transplantation (11,12). In mice, RAPA monotherapy can prevent T1D development (13); however, it is unable to induce disease reversal (14). Moreover, RAPA and IL-2 were found to be synergistic for the prevention of diabetes in NOD mice (13). Consequently, we decided to test whether RAPA could synergize with short-term IL-2 therapy to reverse T1D and reinforce the development of long-term tolerance.In this work, we have further studied the mechanisms of action of IL-2 and RAPA alone or in combination in the NOD model of T1D.     

Pronostic factors in squamous cell carcinoma of the vulva. About 35 cases

OBJECTIVE: To evaluate the pronostic factors of the vulvar cancer. STUDY DESIGN: This is a retrospective study, of 35 cases of squamous cell carcinoma of the vulva diagnosed and treated at Farhat Hached Hospital (Sousse) between January 1991 and December 2002. The study of the pronostic factors is based on analysis of the following parameters obtained after a period varyinf from 6 months to 5 years: clinical data, pre-therapeutique and therapeutic evaluation, pathologic data, outcome and survival rate. RESULTS: The diagnostic was often late with a delay for consultation superior to 6 months in 60% of cases. 80% of the patient wete in stages III and IV of FIGO with an average tumorous size of 3.8 cm and palpable lymph node in 74.2% of the cases. 22 patient underwent vulvectomy with bilateral inguinal node dissection. Adjuvant therapy was carried out in 8 cases. The rate of relapses was 22.7%. The global survival at 5 years of the operated patients was of 40%. The main prognostic factors were: the size tumorale, the degrees of stromal invasion and the lymph node invasion. CONCLUSION: Early detection fo vulvar concer by regular gynecologic examinations and a biopsy of all suspect lesions, allows an early treatment consequently a better prognosis.     

Detection of myocarditis by contrast-enhanced MRI in patients presenting with acute coronary syndrome but no coronary stenosis

PURPOSE: To prospectively assess the use of cardiac MRI with delayed contrast enhancement (DCE) for identifying patients with active myocarditis among those presenting with acute coronary syndrome (ACS) but no coronary stenosis. MATERIALS AND METHODS: A total of 27 consecutive patients (age = 45 +/- 17 years; 14 male) presenting with ACS (chest pain, positive troponin-I) and no coronary stenosis, underwent cardiac MRI 9 +/- 7 days after pain onset and 8 +/- 5 months later (N = 19). Steady-state free-precession pulse (SSFP) sequence was applied for the assessment of myocardial function and both inversion-recovery (IR) and SSFP sequences were used for analyzing the topography and extent of DCE areas. Rest sestamibi-gated-single photon emission CT (SPECT) was also systematically performed. RESULTS: Subepicardial DCE pattern typical of acute myocarditis was documented in 12 patients (44%). Ischemic DCE pattern (transmural or subendocardial focal DCE) was documented in 12 of the 15 remaining patients (44%). Patients with subepicardial DCE had: higher C-reactive protein (CRP) levels (38 +/- 32 vs. 14 +/- 24 mg/mL; P = 0.04), lower Framingham cardiovascular risk (3 +/- 3% vs. 9 +/- 5%; P < 0.001), lower incidence of perfusion SPECT defects (17% vs. 73%; P = 0.01), higher left ventricular (LV) end-diastolic volume (77 +/- 16 vs. 64 +/- 10 mL/m(2); P = 0.02), and higher regression of DCE areas at follow-up (-65 +/- 17% vs. -18 +/- 23%; P = 0.002). CONCLUSION: DCE pattern of active myocarditis can be seen in patients presenting with ACS but no coronary stenosis.     

Atypical deletion of 22q11.2: Detection using the FISH TBX1 probe and molecular characterization with high-density SNP arrays

Despite the heterogeneous clinical presentations, the majority of patients with 22q11.2 deletion syndrome (22q11.2 DS) have either a common recurrent 3 Mb deletion or a less common, 1.5 Mb nested deletion, with breakpoint sites in flanking low-copy repeats (LCR) sequences. Only a small number of atypical deletions have been reported and precisely defined. Haploinsufficiency of the TBX1 gene was determined to be the likely cause of 22q11.2 DS. The diagnostic procedure usually used is FISH using commercially probes (N25 or TUPLE1). However, this test does not contain TBX1, and fails to detect deletions that are either proximal or distal to the FISH probes. Here, we report on two patients with clinical features suggestive of 22q11.2 DS, a male infant with facial dysmorphia, pulmonary atresia, ventricular septal defect, neonatal hypocalcemia, and his affected mother, with facial dysmorphia, learning disabilities, and hypernasal speech. They were tested negative for 22q11.2 DS using N25 or TUPLE1 probes, but were shown deleted for a probe containing TBX1. Delineation of the deletion was performed using high-density SNP arrays (Illumina, 370K). This atypical deletion was spanning 1.89 Mb. The distal breakpoint resided in LCR-D, sharing the same distal breakpoint with the 3 Mb common deletion. The proximal breakpoint was located 105 kb telomeric to TUPLE1, representing a new breakpoint variant that does not correspond to known LCRs of 22q11.2. We conclude that FISH with the TBX1 probe is an accurate diagnostic tool for 22q11.2 DS, with a higher sensitivity than FISH using standard probes, detecting all but the rarest deletions, greatly reducing the false negative rate.     

Age-Related Changes in Inflammatory Response after Experimental Envenomation: Impact on the Susceptibility to <Emphasis Type="Italic">Androctonus australis hector</Emphasis> Venom

In regions at risk of scorpion envenomation, children remain the principal victims; they exhibit severe symptoms and represent a higher mortality rate compared to adults. The pathophysiology of envenomation is related to an excessive inflammatory response; however, no studies have identified the differences in immune responses to scorpion stings and mainly the mechanisms of inflammation between children and adults, which may be a determinant key of the susceptibility of children to scorpion envenomation. In this study, we compared the systemic (blood and lung) and the central (brain) inflammatory responses after injection of Androctonus australis hector (Aah) venom to 7 and 21 postnatal days (pnds) and adult mice by subcutaneous route. Results revealed that 7 and 21 pnd mice were more sensitive to Aah venom than adults and presented also severe systemic and central inflammatory responses characterized by a high activation of immune cells, NO liberation, and lipid peroxidation. Lymphocyte levels were much lower in young animals than in adults; however, neutrophil levels seemed to be higher in immature mice. The antioxidant GSH and catalase levels were more reduced in 7 and 21 pnd mice compared to adults leading to more pronounced tissular alterations and edema formation in lung and brain. These findings show a relationship between the severity of the pathophysiological effects of Aah venom and the age. The vulnerability of immature animals to Aah venom might result from uncontrolled inflammatory response and central nervous system alterations. Data from the present study emphasize the need for the development of age-specific therapeutic modalities.