Systemic complement activation, lung injury, and products of lipid peroxidation.

Previously we have demonstrated that systemic activation of the complement system after intravenous injection of cobra venom factor (CVF) results in acute lung injury as reflected by increases in the vascular permeability of the lung as well as by morphologic evidence of damage to lung vascular endothelial cells. In using the vascular permeability of the lung as the reference, the current studies show a quantitative correlation between lung injury and the appearance in plasma of lipid peroxidation products (conjugated dienes) as well as increased concentrations of lactic dehydrogenase (LDH) and one of its isoenzymes (LDH-4). After injection of CVF, extracts of lungs also showed elevated levels of conjugated dienes, whereas no elevations were found in extracts of liver, kidney, and spleen. There was no evidence in CVF-injected rats of renal or hepatic injury as reflected by the lack of development of proteinuria and the failure to detect increased serum levels of liver-related enzymes. Other peroxidation products identified in plasma of CVF-injected rats involved hydroperoxides and fluorescent compounds with features of Schiff bases. Not surprisingly, malondialdehyde was not found to be a reliable plasma indicator of lipid peroxidation associated with oxygen radical-mediated lung vascular injury. In using a model of oxygen radical-independent lung injury induced by oleic acid, although large amounts of LDH and LDH-4 were found in the plasma, no increases in plasma levels of conjugated dienes were detected. In CVF-injected animals treated with interventions protective against lung injury (neutrophil depletion, catalase, hydroxyl radical scavengers, or iron chelators), there were striking reductions in the plasma levels of conjugated dienes, hydroperoxides, and fluorochromic products. Morphometric analysis of lung sections revealed that the protective interventions did not interfere with the accumulation of neutrophils in lung interstitial capillaries after systemic activation of complement. In vitro studies with phorbol-stimulated neutrophils failed to demonstrate appearance of conjugated dienes, suggesting that the dienes appearing in plasma of CVF-injected animals are not the result of autotoxic changes in neutrophils. The data presented in this paper suggest that acute lung injury mediated by oxygen radicals derived from phagocytic cells can be monitored by the appearance in plasma of products of lipid peroxidation.     

Targeting prostate cancer: Prostate-specific membrane antigen based diagnosis and therapy

The high incidence rates of prostate cancer (PCa) raise demand for improved therapeutic strategies. Prostate tumors specifically express the prostate-specific membrane antigen (PSMA), a membrane-bound protease. As PSMA is highly overexpressed on malignant prostate tumor cells and as its expression rate correlates with the aggressiveness of the disease, this tumor-associated biomarker provides the possibility to develop new strategies for diagnostics and therapy of PCa. Major advances have been made in PSMA targeting, ranging from immunotherapeutic approaches to therapeutic small molecules. This review elaborates the diversity of PSMA targeting agents while focusing on the radioactively labeled tracers for diagnosis and endoradiotherapy. A variety of radionuclides have been shown to either enable precise diagnosis or efficiently treat the tumor with minimal effects to nontargeted organs. Most small molecules with affinity for PSMA are based on either a phosphonate or a urea-based binding motif. Based on these pharmacophores, major effort has been made to identify modifications to achieve ideal pharmacokinetics while retaining the specific targeting of the PSMA binding pocket. Several tracers have now shown excellent clinical usability in particular for molecular imaging and therapy as proven by the efficiency of theranostic approaches in current studies. The archetypal expression profile of PSMA may be exploited for the treatment with alpha emitters to break radioresistance and thus to bring the power of systemic therapy to higher levels.     

Australia Antigen in Cord Blood

Abstract. Australia antigen was demonstrated in cord blood and consecutive blood samples of a new-born from a mother who had suffered from serum hepatitis during her pregnancy.     

Clinical evaluation of direct pulp capping using a calcium silicate cement—treatment outcomes over an average period of 2.3 years

Objectives

This study aims to assess the treatment outcomes of direct pulp capping with a calcium silicate cement (Biodentine) after caries excavation.

Materials and methods

A total of 245 teeth of 226 patients diagnosed to be clinical healthy or showing spontaneous pain were directly capped. The teeth were examined 0.19 to 7.4 (mean 2.3 ± 2.04) years after treatment. The following data were recorded: age and sex of the patient, type of tooth and restoration (glass ionomer cement [GIC], amalgam, composite resin, ceramic, gold) and symptoms before or after treatment. The evaluation of the treatment was carried out by sensibility and percussion testing and by the patient’s questioning. A positive sensibility test, a negative percussion test, the absence of swelling and discomfort were considered as treatment success. Survival analysis was performed using the Kaplan-Meier, log-rank, Chi-square and Fisher’s exact test, respectively.

Results

After an average period of 2.3 years, 86.0% of the teeth remained vital; the survival rate after 7.4 years was 83.4%. The treatment outcome was significantly worse for cavities restored with GIC compared to all other restorative materials (p < 0.05). All other evaluated factors had no significant influence on the success rate (p > 0.05).

Conclusion

Exposed pulps of asymptomatic vital permanent teeth and teeth with spontaneous pain before treatment can be successfully capped directly using Biodentine. A subsequent restoration with GIC does not appear to be suitable as it significantly reduces the success of the treatment.

Clinical relevance

Direct pulp capping can be done successfully with this type of calcium silicate cement.

     

P53 immunohistochemical expression does not correlate with clinical features in 207 carcinomas of the oral cavity and in the head and neck region

Objectives

The present study aims to investigate the relevance of immunohistochemical p53 expression in carcinomas of the oral cavity and of the head and neck region. Long-term clinical and histopathological follow-up findings as well as HPV status are correlated with the results of this examination.

Materials and methods

Sections made from two tissue arrays composed of 222 oral squamous cell carcinomas and 427 squamous cell carcinomas of the head and neck region, respectively, were examined for p53 expression and Ki-67 index by means of immunohistochemistry. Correlation of long-term clinical findings of the patients and pathological features of tumours with laboratory results were examined statistically.

Results

No significant correlation was found between the p53 immunohistochemical expression in the 207 oral carcinomas and features of the tumours and patient outcomes. There was no significant association between the Ki-67 labelling index and the p53 expression.

Discussion

Our failure in detecting any association of the p53 immunohistochemical expression regardless of HPV status with clinical features of these tumours suggests it lacks a prognostic value for squamous cell carcinomas of the oral cavity.

Clinical relevance

The prognostic value of p53 immunostaining in oral squamous carcinoma is not clarified yet. In the present study, there is no impact on any prognostical item nor even a correlation with cell proliferation (Ki-67) regardless of HPV status.     

Participant Engagement and Reactance to a Short,Animated Video About Added Sugars: Web-based Randomized Controlled Trial

BackgroundShort, animated story-based (SAS) videos are a novel and promising strategy for promoting health behaviors. To gain traction as an effective health communication tool, SAS videos must demonstrate their potential to engage a diverse and global audience. In this study, we evaluate engagement with a SAS video about the consumption of added sugars, which is narrated by a child (a nonthreatening character), a mother (a neutral layperson), or a physician (a medical expert).ObjectiveThis study aims to (1) assess whether engagement with the sugar intervention video differs by narrator type (child, mother, physician) and trait proneness to reactance and (2) assess whether the demographic characteristics of the participants (age, gender, education status) are associated with different engagement profiles with the sugar intervention video.MethodsIn December 2020, after 4013 participants from the United Kingdom completed our randomized controlled trial, we offered participants assigned to the placebo arms (n=1591, 39.65%) the choice to watch the sugar intervention video (without additional compensation) as posttrial access to treatment. We measured engagement as the time that participants chose to watch the 3.42-minute video and collected data on age, gender, education status, and trait reactance proneness. Using ordinary least squares regression, we quantified the association of the demographic characteristics and trait reactance proneness with the sugar video view time.ResultsOverall, 66.43% (n=1047) of the 1576 participants in the 2 placebo arms voluntarily watched the sugar intervention video. The mean view time was 116.35 (52.4%) of 222 seconds. Results show that view times did not differ by narrator (child, mother, physician) and that older participants (aged 25-59 years, mean = 125.2 seconds) watched the sugar video longer than younger adults (aged 18-25 years, mean = 83.4 seconds). View time remained consistent across education levels. Participants with low trait reactance (mean = 119.3 seconds) watched the intervention video longer than high-trait-reactance participants (mean = 95.3 seconds), although this association did not differ by narrator type.ConclusionsThe majority of participants in our study voluntarily watched more than half of the sugar intervention video, which is a promising finding. Our results suggest that SAS videos may need to be shorter than 2 minutes to engage people who are young or have high trait proneness to reactance. We also found that the choice of narrator (child, mother, or physician) for our video did not significantly affect participant engagement. Future videos, aimed at reaching diverse audiences, could be customized for different age groups, where appropriate.Trial RegistrationGerman Clinical Trials Register DRKS00022340; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022340International Registered Report Identifier (IRRID)RR2-10.2196/25343     

Vascularization and expression of hypoxia-related tissue factors in intracranial ependymoma and their impact on patient survival

We investigated angiogenic patterns and expression of hypoxia-related tissue factors and their prognostic impact in 100 cases of intracranial ependymoma. Angiogenic patterns were evaluated by anti-CD34 immunolabeling. Hypoxia-related factors carbonic anhydrase 9 (CA9) and hypoxia-inducible factor 1 alpha (HIF-1) were visualized by immunohistochemistry, and vascular endothelial growth factor (VEGF) mRNA by in situ hybridization. Expression patterns of VEGF and CA9 are similar with regard to distribution (perinecrotic) and extent. HIF-1 expression occurs in a significantly smaller fraction of cases and only in a few tumor cells without clear association with necrosis. Expression of VEGF and CA9, but not HIF-1, is associated with a bizarre angiogenic subtype. Combined expression of two or three hypoxia markers (high hypoxia score) associates with presence of necrosis, high proliferation index, bizarre vascular pattern, and increased cellularity. Univariate analysis indicated that patients with high hypoxia score had significantly shorter survival. On multivariate analysis, only proliferation index and extent of resection remained independent predictive factors. We conclude that bizarre vascular pattern, necrosis and high hypoxia score are frequently detectable in intracranial ependymoma, but seem less important for patient outcome than tumor cell proliferation.     

An extract of feverfew inhibits interactions of human platelets with collagen substrates

The interaction of platelets with surfaces coated with collagens of type III (C III) or IV (C IV) has been studied by measuring the deposition of 51-Cr-labeled platelets and by scanning electron microscopy (SEM). Experiments were performed using platelet-rich plasma (PRP) and suspensions of gel-filtered platelets (GFP). Platelets were deposited on C III mainly as surface-bound aggregates. In contrast they were deposited on C IV mainly as spread forms of individual cells. Formation of aggregates on C III was more extensive for PRP than for GFP; in contrast platelet spreading on C IV was more extensive for GFP than for PRP. The effects of an extract of the plant feverfew on platelet-collagen interactions were determined. Feverfew extract inhibited the deposition of 51-Cr-labeled platelets on both C III and C IV in a dose-dependent way. Similar concentrations of extract were needed to inhibit the formation of surface-bound aggregates and to inhibit platelet spreading in both PRP and GFP.