Effect of human saliva on surface degradation of composite resins

Abstract – The amount of methacrylic acid produced by incubation of the dimethacrylate ester TEGDMA in human whole saliva was measured. The conversion rate of TEGDMA was determined in stimulated saliva from dental students and in unstimulated saliva from both dental students and patients. The differences in mean conversion rate measured in the three groups were not statistically significant ( P= 0.346). The mean conversion rate ± SD for all saliva samples was 4.54 ± 3.24 μmol MAA/L. h. The surface of BISGMA/TEGDMA-polymer specimens treated with porcine liver esterase in activities equivalent to those found in human saliva exhibited a lower Wallace microhardness than the surface of untreated specimens. Polymer specimens incubated in human saliva exhibited a similar reduction in the microhardness. The results demonstrated that enzymes in human saliva are capable of softening the surface of dimethaerylate polymers presumably by inducing a hydrolysis of methacrylate ester bonds. The mechanical removal of a surface layer softened by hydrolases will expose a new surface layer to enzymatic attack. The enzymatic softening may thus contribute to the in vivo wear of composite restorations.     

Hemodynamic Deterioration Following Radiofrequency Ablation of the Atrioventricular Conduction System

Radiofrequeucy ablation of the atrioventricular conduction system (ACS) has become an estoblished theTapy for patients with drug refroctory atrial fibrillation. We observed eight patients with hemodynamic deterioration ofteT radiofrequency oblotion of the otTioventTicular conduction system. As we found hemodynamic deterioration related to worsening mitral regurgitation, we compared the clinical history, eiectrophysiologicai, ond echocardiographic dato from the patients with hemodynamic deteriorotion and worsening mitral regurgitation (group 1) to those without hemodynamic deterioration and stable mitral regurgitation after the procedure (group 2). Eight out of 108 patients (7.4%) undergoing ablation of the ACS deteriorated hemodynamically with acute pulmonary edema in three and congestive heart failure in five patients occurring at a mean of 3 and 8 weeks, respectively, after the procedure. Three of these patients were referred for mitral valve surgery. Two patients underwent ablation using a left-sided approach. A right-sided approach was used in five patients. In one patient, a left- and right-sided approach was used. Compared to group 2 patients, group 1 patients had significantly higher left ventricular end-diastolic diameters (64 ± 6 mm vs 56 ± 9 mm) at baseline despite similar fractional shortening (32%± Il% vs 34%± 13%), left ventricular end-systolic diameters (43 ± 9 mm vs36 ± 7 mm) and degree of mitral regurgitation (1.4 ± 1.1 vs 1.4 ±0.7) on echocardiographic analysis. Thus, hemodynamic deterioration together with progression of mitral regurgitation is a potential complication of ablation of the ACS (up to 7.4%). Patients with high left ventricular end-diastolic diameters ond moderate mitral regurgitation at baseline seem prone to this complication.     

Autonomic Dysfunction and New‐Onset Atrial Fibrillation in Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: A CARISMA Substudy

Predicting New‐Onset AF. Background: Atrial fibrillation (AF) increases morbidity and mortality in patients with previous myocardial infarction and left ventricular systolic dysfunction. The purpose of this study was to identify patients with a high risk for new‐onset AF in this population using invasive and noninvasive electrophysiological tests. Methods: The study included 271 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study with an acute myocardial infarction (AMI) and left ventricular ejection fraction ≤40% without previous AF at enrollment. Within 21 days after the AMI, an implantable loop recorder was inserted and used to diagnose AF over the 2‐year study duration. The following tests were performed: heart rate variability (HRV) and turbulence (HRT) analyses from repeated 24‐hour Holter recordings, 2‐dimensional (2D)‐echocardiograms, exercise test, and programmed electrophysiologic stimulation. Results: A total of 101 patients (37%) developed AF during the study. Predictive measures included several indexes of HRV including reduced low‐frequency (LF) power from spectral HRV analysis (adjusted HR = 1.6, P = 0.034), HRT slope ≤2.5 (HR = 1.6, P = 0.032) and Detrended Fluctuation Analysis (DFA1) from HRV analysis (HR = 1.8, P = 0.011); all are measures of cardiac autonomic nervous system dysfunction. Combined with age >60 years, low values for LF, HRT slope, and DFA1 provided a powerful risk score for prediction of new‐onset AF (1–2 points: HR = 4.3, P = 0.001, 3–4 points: HR = 7.0, P < 0.001). Conclusion: Abnormal HRV and HRT parameters, which are associated with disturbances in the cardiac autonomic regulation, are associated with increased risk of new‐onset AF independently of conventional clinical risk variables. (J Cardiovasc Electrophysiol, Vol. 21, pp. 983‐990, September 2010)     

Do women with epilepsy have increased frequency of menstrual disturbances?

PROBLEM: Menstrual disorders, reduced fertility and sexual problems seem to be more frequent in women with epilepsy than in the general population. Most investigations concerning menstrual disturbances in epilepsy patients, however, are small and based on selected materials. We therefore wanted to investigate the frequency of menstrual disturbances in a large, unselected population of epilepsy patients. METHODS: A retrospective, questionnaire study of a cohort of female outpatients, aged 18-45 was conducted. Each patient chose a close female friend who served as control, to optimise matching regarding age and lifestyle. RESULTS: Answers were received from 265 patients and 142 controls. Menstrual disturbances were more frequent in patients with epilepsy (48.0%) than in controls (30.7%) (P=0.004). Menstrual disturbances were more frequent in patients on polytherapy versus monotherapy (P=0.049) and more frequent in patients with high seizure frequency (>5seizures/year) compared to patients with a lower seizure frequency or those seizure free (P=0.006). The frequency of menstrual disturbances was higher in patients on valproate compared to carbamazepine monotherapy (P=0.045). CONCLUSION: This investigation confirms that women with epilepsy have an increased frequency of menstrual disturbances compared to women without epilepsy. In women with high seizure frequency and in those on polytherapy, the frequency of menstrual disturbances are further increased. The highest frequency of menstrual disturbances occurred in women using valproate.     

Potency of a Complex Mixture of Polychlorinated Dibenzo-p-dioxin, Dibenzofuran, and Biphenyl Congeners Compared to 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Causing Fish Early Life Stage Mortality

Use of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity equivalentsconcentration (TEC) assumes that polychlorinated di benzo-p-dioxins(PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) act additivelyand via a common mechanism to cause toxicity. To test theseassumptions, 11 TCDD-like congeners and three non-TCDD-likecongeners were combined at ratios typically found in Lake Michiganlake trout. The potency of the mixture, expressed as TEC basedon fish-specific toxic equivalency factors, was compared toTCDD for producing lake trout and rainbow trout early life stagemortality. Signs of toxicity following exposure of newly fertilizedeggs to the mixture or to TCDD were indistinguishable; sac frymortality associated with blue-sac disease, and slopes of thedose-response curves for percentage sac fry mortality versusegg TEC or versus egg TCDD were parallel. However, the mixturedose-response curves were significantly shifted to the rightof the TCDD dose-response curves by 1.3- to 1.8-fold as illustratedby LD₅₀ values. Following exposure to the mixture or TCDD, LD₅₀sfor lake trout early life stage mortality were 97 (89–110)pg TE/g egg and 74 (70–80) pg TCDD/g (LD₅₀, 95% fiduciallimits) and for rainbow trout were 362 (312–406) pg TE/gegg and 200 (148–237) pg TCDD/g egg. These data suggestthat TCDD-like congeners act via a common mechanism to causetoxicity during trout early development, but may not act strictlyadditively when combined in a mixture of TCDD- and non-TCDD-likecongeners at ratios found in Great Lakes fish. The deviationfrom additivity, however, is less than current safety factorsof 10-fold commonly applied in ecological risk assessments,providing support for the continued use of a TE additivity modelfor assessing risk posed by complex mixtures of PCDDs, PCDFs,and PCBs to fish.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Increased p53 immunoreactivity in proliferative inflammatory atrophy of prostate is related to focal acute inflammation

Proliferative inflammatory atrophy (PIA) of prostate has been proposed as a precursor lesion of prostate cancer. The aim of the current study was to evaluate the expression of p53 protein in PIA lesions and to investigate the relationship between p53 staining and Ki‐67, glutathione S‐transferase‐π (GSTP1) and cyclooxygenase‐2 (COX‐2) immunohistochemical expression. The results revealed that p53 nuclear immunostaining appeared in PIA lesions in 2.1±3.4% (mean±SD) of the basal and 0.9±2.3% of the luminal epithelial cells. Both these values were significantly higher than those in normal‐appearing acini (p<0.0001). Increased p53 expression in luminal cells was related to focal infiltration of polymorphonuclear leucocytes. A positive correlation between p53 expression and Ki‐67 was found in COX‐2‐positive PIA lesions (r=0.610, p<0.0001). Half of the p53‐positive epithelial cells expressed diffuse GSTP1 immunostaining in the same lesions. The present study demonstrates an increased p53 expression in PIA lesions, and inflammation, especially acute inflammation, may play a role in the induction of p53 over‐expression, particularly as cells in PIA lesions are known to have a reduced defence against DNA damage.     

Unexpected lability of cysteine acetamidomethyl thiol protecting group Tyrosine ring alkylation and disulfide bond formation upon acidolysis

Cleavage and deprotection of the peptidyl resin H-Asn-Gly-Gly-Cys(Acm)-Glu(OBu^t)-Gln-Tyr(Bu^t)-Cys(Acm)-Ser(Bu^t)-Asp(OBu^t)-[(p-alkoxy)benzyloxy polystyrene resin] using standard conditions with various trifluoroacetic acid-containing mixtures were found to result in partial removal of ordinarily acid-stable S-Acm groups. Thus, apart from the desired peptide H-Asn-Gly-Gly-Cys(Acm)-Glu-Gln-Tyr-Cys(Acm)-Ser-Asp-OH, a disulfide-cyclic peptide derivative was also isolated. Furthermore, it was found that in another major by-product of the peptide resin cleavage the tyrosine side chain had been alkylated with an Acm group in a position ortho to the phenolic function. The formation of both by-products could be suppressed by carrying out the cleavage/deprotection reaction at higher dilution and by inclusion of scavengers such as phenol. An authentic sample of the disulfide-cyclic peptide was obtained by oxidation of H-Asn-Gly-Gly-Cys-Glu-Gln-Tyr-Cys-Ser-Asp-OH using Ellman's reagent. © Munksgaard 1997.     

Temporary Stenting as a Bridge to Surgery

Abrupt occlusion of the coronary artery during PTCA is a relatively common complication. The majority of the acute occlusions occur when there is a significant dissection at the site of the balloon expansion. The use of a temporary stent, which can be expanded and collapsed intraluminally, allowing repositioning and finally removal of the device, is reported in this article.     

Preparation and properties of Nα-Bpoc-amino acid pentafluorophenyl esters

The preparation and properties are reported of several N^x-Bpoc -amino acid pentafluorophenyl esters, including those bearing tert-butyl-, allyl- and trityl-based protecting groups. These derivatives have been used in the solid-phase peptide synthesis of sevral short peptides.