Oral cadmium exposure during rat pregnancy: assessment of transplacental micronutrient transport and steroidogenesis at term

Diet is the main source of cadmium (Cd) exposure. Gastrointestinal absorption increases during pregnancy. Cadmium accumulated in the placenta may interfere with nutrient transport to the foetus. Data on the potential of Cd to act as a steroid disruptor of pregnancy are limited. We evaluated the effects of oral Cd exposure during pregnancy on placental function in micronutrient transfer to the foetus and steroidogenesis in Wistar rats (regular 4‐day cyclers) that mated with unexposed males. Pregnant rats were randomly assigned to a Cd group exposed orally to 50 mg Cd l^–1 (CdCl₂xH₂O dissolved in demineralized water), ≈7.5 mg Cd kg^–1 a day, during 20 days of gestation and control (supplied with demineralized water). Non‐pregnant rats were treated under the same experimental conditions. On day 20, all of the rats were killed and samples were taken for element analyses (by electrothermal atomic absorption spectrometry). Progesterone and testosterone were measured in serum and placenta‐derived samples (by immunoenzymometric assay and/or enzyme‐linked immunosorbent assay). In the exposed rats, Cd increased in blood and organs, more in pregnant rats, and in placenta and foetus whereas zinc increased in liver. Iron decreased in maternal organs and in foetus, whereas zinc decreased in maternal kidney and placenta. Liver copper was lower and kidney copper higher in all pregnant vs. non‐pregnant rats. Steroids in serum and placenta did not change. In conclusion, oral Cd exposure during rat pregnancy does not affect progesterone and testosterone at term. Transplacental iron and zinc handover are disrupted, which may put at risk the maintenance of foetal nutrition and viability. Copyright © 2014 John Wiley & Sons, Ltd.     

The evolutionary arms race between NK cells and viruses: Who gets the short end of the stick?

NK cells are innate lymphocytes that play a key role in the control of various viral infections. Recent studies indicate that NK cells may acquire some features of adaptive immune cells, including the formation of long‐lived memory cells. A large and growing body of data indicates that NK cells regulate the adaptive immune response as well. The function and the activation status of NK cells are tightly regulated by signals induced by a broad range of inhibitory and activating cell surface receptors and cytokines released by other immune cells. Here, we review the function of mouse NK‐cell receptors involved in virus control and in the regulation of the adaptive immune response. In addition, we discuss viral strategies used to evade NK‐cell‐mediated control during infection. Finally, the role of several activating Ly49 receptors specific for mouse cytomegalovirus (MCMV), as well as some controversial issues in the field, will be discussed.     

High-content live-cell imaging assay used to establish mechanism of trastuzumab emtansine (T-DM1)-mediated inhibition of platelet production

Proplatelet production represents a terminal stage of megakaryocyte development during which long, branching processes composed of platelet-sized swellings are extended and released into the surrounding culture. Whereas the cytoskeletal mechanics driving these transformations have been the focus of many studies, significant limitations in our ability to quantify the rate and extent of proplatelet production have restricted the field to qualitative analyses of a limited number of cells over short intervals. A novel high-content, quantitative, live-cell imaging assay using the IncuCyte system (Essen BioScience) was therefore developed to measure the rate and extent of megakaryocyte maturation and proplatelet production under live culture conditions for extended periods of time. As proof of concept, we used this system in the present study to establish a mechanism by which trastuzumab emtansine (T-DM1), an Ab-drug conjugate currently in clinical development for cancer, affects platelet production. High-content analysis of primary cell cultures revealed that T-DM1 is taken up by mouse megakaryocytes, inhibits megakaryocyte differentiation, and disrupts proplatelet formation by inducing abnormal tubulin organization and suppressing microtubule dynamic instability. Defining the pathways by which therapeutics such as T-DM1 affect megakaryocyte differentiation and proplatelet production may yield strategies to manage drug-induced thrombocytopenias.     

Short pain-provoked head-up tilt test for the confirmation of vasovagal syncope

We investigated a short pain-provoked head-up tilt (PP-HUT) and the Calgary Syncope Symptom Score in a group of patients with clinically diagnosed vasovagal syncope and group of neurological patients without transient loss of consciousness. We included 127 consecutive patients who were investigated in our laboratory. The group 1 included 56 patients who after appropriate investigations were diagnosed with vasovagal syncope. The group 2 included 70 neurological patients without transient loss of consciousness. The subjects were tilted to 70° for a maximum period of 10 min or until symptoms occurred. If there were no symptoms after initial 10 min, a painful stimulus with the insertion of 0.7 mm needle into the dorsum of hand subcutaneously for 30 s was performed with the patient in the tilted for further 5 min. Calgary Syncope Symptom Score was calculated for all patients. In the group 1, significantly higher number of patients had positive results on PP-HUT (36 vs. 6 patients, respectively; p < 0,001). There was no difference in the presence of orthostatic hypotension (8 vs. 15 patients, respectively; p = 0.36) or postural orthostatic tachycardia syndrome (3 vs. 1 patient, respectively; p = 0.32) between groups. PP-HUT had sensitivity of 65.9 % (95 % CI 0.49–0.79) and specificity of 89.7 % (95 % CI 0.75–0.97). The CSSS had sensitivity of 58.5 % (95 % CI 0.42–0.73) and specificity of 46.1 % (95 % CI 0.30–0.63). PP-HUT has a higher diagnostic rate than the CSSS and provides a rapid alternative to conventional methods.     

Postural orthostatic tachycardia syndrome associated with multiple sclerosis

BackgroundThe aim of this study was to determine if there is a difference in the frequency of postural orthostatic tachycardia syndrome (POTS) in patients with multiple sclerosis (MS) compared to patients with symptoms of orthostatic intolerance and with no evidence of MS or other neurological illness.MethodsWe analyzed data gathered from 293 patients who underwent the head-up tilt table test protocol. Group 1 included prospectively analyzed 112 with MS and group 2 included retrospectively analyzed 181 patients who were evaluated because of symptoms of orthostatic intolerance, and with no evidence of MS or other neurological illness. If POTS was identified the head-up tilt table test was repeated and supine as well as standing serum epinephrine and norepinephrine were determined.ResultsPOTS was identified in 39 patients: 21 (19%) in the MS group comparing to 18 (10%) in the non MS group (p = 0.035). There was no difference between groups in the occurrence of POTS associated syncope (p = 0.52). There was no difference between groups in the epinephrine or norepinephrine in supine and standing positions. While both standing epinephrine and norepinephrine levels were significantly higher compared to levels in the supine position in the non MS group, only standing norepinephrine levels were significantly higher in the MS group.ConclusionsThe results of this study suggest that POTS is associated with MS.     

The effect of two different bracket types on the salivary levels of S mutans and S sobrinus in the early phase of orthodontic treatment

Objective:To determine the difference in the levels of Streptococcus mutans and S sobrinus in stimulated saliva in orthodontic patients with different bracket types (stainless steel and esthetic brackets) using polymerase chain reaction and cultivation method.Materials and Methods:Thirty-two patients, aged 13 to 30 years, were selected following these criteria: 1) orthodontic treatment indication, 2) systemic health, and 3) no tobacco and antibiotic consummation for three months prior to the commencement of the study. Patients were divided into two groups according to the bracket type; 16 patients formed the conventional bracket group (stainless steel brackets), and 16 patients formed the esthetic bracket group (plastic brackets). The levels of S mutans and S sobrinus in stimulated whole saliva samples were collected prior to fixed orthodontic appliance placement (T1) and 12 weeks after placement (T2), as were the Decayed, Missing, and Filled Surface Index (DMFS) and Oral Hygiene Index-Simplified (OHI-S). Mann-Whitney, Wilcoxon, and chi-square tests were used for statistical analysis.Results:Statistical analysis (chi-square test) showed no difference in S mutans and S sobrinus counts among patients with different brackets at either T1 or T2. There was no difference in total bacteria counts after fixed orthodontic appliance placement.Conclusion:The number of colony-forming units of S mutans and S sobrinus in stimulated saliva samples does not seem to be significantly different between patients with stainless steel brackets and patients with plastic brackets.     

Genotoxicity in gingival cells of patients undergoing tooth restoration with two different dental composite materials

Objectives

Dental composite materials come into direct contact with oral tissue, especially gingival cells. This study was performed to evaluate possible DNA damage to gingival cells exposed to resin composite dental materials.

Materials and methods

Class V restorations were placed in 30 adult patients using two different composite resins. The epithelial cells of the gingival area along the composite restoration were sampled prior to and after 7, 30, and 180 days following the restoration of the tooth. DNA damage was analysed by comet and micronucleus assays in gingival exfoliated epithelial cells.

Results

The results showed significantly higher comet assay parameters (tail length and % DNA in the tail) within periods of 30 and 180 days. The micronucleus test for the same exposure time demonstrated a higher number of cells with micronuclei, karyolysis, and nuclear buds. Results did not reveal any difference between the two composite materials for the same duration of exposure.

Conclusion

Based on the results, we can conclude that the use of composite resins causes cellular damage. As dental composite resins remain in intimate contact with oral tissue over a long period of time, further research on their possible genotoxicity is advisable.

Clinical relevance

Long-term exposure of gingival cells to two different composite materials demonstrated certain DNA damage. However, considering the significant decline in micronuclei frequency after 180 days and efficiency in the repair of primary DNA damage, the observed effects could not be indicated as biologically relevant.