Comparative morphological differences between umbilical cords from chronic hypertensive and preeclamptic pregnancies

To compare morphological changes in the umbilical cords from chronic hypertensive and preeclamptic patients having normal or pathological umbilical artery Doppler ultrasonographic results. Umbilical cords from 34 normotensive, 31 chronic hypertensive and 70 preeclamptic women with normal and abnormal Doppler flow velocity waveforms (FVW) at 35-40 gestational weeks were studied. Morphological changes in the umbilical cords were examined on formalin-fixed, paraffin-embedded sections. The total umbilical cord area, total vessel area, and wall thickness of umbilical vessels were measured in systematic random samples using unbiased stereology methods. An ANOVA test was used for statistical analysis. In the chronic hypertensive and preeclamptic groups with normal Doppler FVW, the thickness of the umbilical cord vessels remained nearly constant, whereas both the total area and the lumen area were reduced. These changes correlate with the histopathological findings, suggesting a mainly vasoconstrictive effect. By contrast, analysis of the preeclamptic group with pathologic Doppler FVW showed a comparable reduction of all parameters of the umbilical cord. Histopathological findings were related to smaller, contracted smooth muscle cells of the vessel wall, which is suggestive of a predominant hypoplastic mechanism. As a result of reduced uteroplacental perfusion, fetal hypoxia and intrauterine growth retardation become unavoidable in preeclampsia. The histopathological changes in the umbilical cord between the chronic hypertensive and preeclamptic patients depend on the Doppler results. In conclusion, the umbilical artery Doppler FVW indices provide good values for predicting intrauterine growth retardation in preeclamptic patients.     

Changed Bcl:Bax ratio in endometrium of patients with unexplained infertility

Apoptosis has been shown to be an important regulator of endometrial function during the menstrual cycle and implantation. Recently, some possible implantation defects were identified in patients with unexplained infertility. In this study, we investigated the role of spontaneous apoptosis, which is regulated by death regulatory genes, such as Bcl-2, Bax, p53, and isoenzymes of nitric oxide synthases; eNOS and iNOS during the implantation window in women with unexplained infertility. Endometrial samples were evaluated from fertile (n=15) and unexplained-infertile women (n=15) during post-ovulatory 7th or 8th day of their menstrual cycles. Apoptotic cells were detected using the dUTP nick-end labelling assay and Bcl-2, Bax, p53, iNOS and eNOS were assessed immunohistochemically. Reduced apoptotic cells, weak immunoreactivity of p53 and strong immunoreactivity of Bcl-2 were observed in the unexplained-infertile group compared with the fertile group (p<0.001). Bax intensity was similar in both groups. While weak iNOS immunoreactivity was detected in both groups, moderately increased eNOS immunoreactivity was observed in infertile cases. Spontaneous apoptosis is reduced in the endometrium of unexplained-infertile women, and is associated with the changed Bcl-2:Bax ratio. This finding may be a contributing factor to defective implantation causing infertility in this group of patients.     

Nasal mucosal expression of nitric oxide synthases in patients with allergic rhinitis and its relation to asthma.

BACKGROUND: Nitric oxide (NO) has contradictory roles in the pathophysiology of allergic inflammation in both allergic rhinitis (AR) and asthma. Small amounts of NO produced by constitutive NO synthase (NOS) is anti-inflammatory, whereas large amounts produced by inducible NOS (iNOS) are proinflammatory. OBJECTIVE: To investigate the difference in constitutive endothelial NOS (eNOS) and iNOS expression in nonallergic and allergic mucosa and the possible relation of this to the coexistence of asthma in seasonal AR. METHODS: Seventeen patients (10 women and 7 men) with seasonal AR and 9 nonallergic patients (5 women and 4 men) with nasal septum deviation were enrolled. Inferior turbinate nasal biopsy specimens were obtained in all. Levels of eNOS and iNOS expressed as immunohistochemical scores (HSCOREs) were determined immunohistochemically from the specimens. RESULTS: The mean +/- SD HSCOREs for eNOS in patients with seasonal AR were not significantly different from those of the nonallergic controls (1.85 +/- 0.78 vs 1.63 +/- 0.54; P = .12). On the other hand, the mean +/- SD HSCOREs for iNOS were significantly higher in patients with seasonal AR (1.75 +/- 0.75 vs 0.71 +/- 0.6; P = .004). Furthermore, although eNOS expression was not different between seasonal AR patients with and without asthma, the mean +/- SD HSCOREs for iNOS were significantly higher in the patients with asthma (1.93 +/- 0.78 vs 1.65 +/- 0.55; P = .01). CONCLUSION: Increased expression of iNOS might have a role in the development of allergic inflammation in upper and lower airways and in comorbidity of AR and asthma.     

Current status of micro/nanomotors in drug delivery

Abstract

Synthetic micro/nanomotors (MNMs) are novel, self-propelled nano or microscale devices that are widely used in drug transport, cell stimulation and isolation, bio-imaging, diagnostic and monitoring, sensing, photocatalysis and environmental remediation. Various preparation methods and propulsion mechanisms make MNMs “tailormade” nanosystems for the intended purpose or use. As the one of the newest members of nano carriers, MNMs open a new perspective especially for rapid drug transport and gene delivery. Although there exists limited number of in-vivo studies for drug delivery purposes, existence of in-vitro supportive data strongly encourages researchers to move on in this field and benefit from the manoeuvre capability of these novel systems. In this article, we reviewed the preparation and propulsion mechanisms of nanomotors in various fields with special attention to drug delivery systems.     

Accounting for Attribute‐Level Non‐Attendance in a Health Choice Experiment: Does it Matter?

An extensive literature has established that it is common for respondents to ignore attributes of the alternatives within choice experiments. In most of the studies on attribute non‐attendance, it is assumed that respondents consciously (or unconsciously) ignore one or more attributes of the alternatives, regardless of their levels. In this paper, we present a new line of enquiry and approach for modelling non‐attendance in the context of investigating preferences for health service innovations. This approach recognises that non‐attendance may not just be associated with attributes but may also apply to the attribute's levels. Our results show that respondents process each level of an attribute differently: while attending to the attribute, they ignore a subset of the attribute's levels. In such cases, the usual approach of assuming that respondents either attend to the attribute or not, irrespective of its levels, is erroneous and could lead to misguided policy recommendations. Our results indicate that allowing for attribute‐level non‐attendance leads to substantial improvements in the model fit and has an impact on estimated marginal willingness to pay and choice predictions.Copyright © 2014 John Wiley & Sons, Ltd.     

P2X7 receptor antagonist delivery vehicle based on photocrosslinked amphiphilic hybrid gels

We report here a method for the synthesis of a unique hybrid gel system for the sustained delivery of P2X7 receptor (P2X7R) antagonist. P2X7R has been reported as a key mediator in inflammatory processes and controlled delivery of this molecule would be critical for the treatment of inflammatory arthritis. The hybrid gel designed here for the sustained delivery of P2X7R antagonists is based on crosslinked hydrophobic styrene-butadiene-styrene (SBS) polymer as a continuous network, where hydrogel particles prepared with hydrophilic poly(ethylene glycol) (PEG) were embedded into this system. PEG hydrogel particle-incorporated SBS gels were characterized through electron microscopy, water contact angle observations, and strong mechanical properties were confirmed through nanoindentation measurements. The release of P2X7R antagonist from these hybrid hydrogel-elastomer system demonstrated a sustained drug release profile up to 28 days at physiological pH, which was not observed in earlier reports. We obtained drug release percentages ranging from 49.72% to 93.04% which indicated the tunability of release through SBS crosslinking and hydrophilic/hydrophobic nature of SBS. This tunability is significant to achieve simultaneous improvements in drug efficacy with reduced side effects. CellTiter-Glo luminescence measurements using human kidney cells revealed that these networks are non-toxic and highly biocompatible with percent cell viabilities of higher than 85%. The approach presented here with crosslinked, amphiphilic and elastic SBS gel systems is not only promising for extended release of P2X7R antagonist but could also allow for incorporation of different molecules so that simultaneous/sequential and extended release profiles for therapeutic molecules could be achieved.

We report here a method for the synthesis of a unique hybrid gel system for the sustained delivery of P2X7 receptor (P2X7R) antagonist.     

Discrimination between non-functioning pituitary adenomas and hypophysitis using machine learning methods based on magnetic resonance imaging‑derived texture features

Purpose

Hypophysitis is a heterogeneous condition that includes inflammation of the pituitary gland and infundibulum, and it can cause symptoms related to mass effects and hormonal deficiencies. We aimed to evaluate the potential role of machine learning methods in differentiating hypophysitis from non-functioning pituitary adenomas.

Methods

The radiomic parameters obtained from T1A-C images were used. Among the radiomic parameters, parameters capable of distinguishing between hypophysitis and non-functioning pituitary adenomas were selected. In order to avoid the effects of confounding factors and to improve the performance of the classifiers, parameters with high correlation with each other were eliminated. Machine learning algorithms were performed with the combination of gray-level run-length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray-level co-occurrence entropy.

Results

A total of 34 patients were included, 17 of whom had hypophysitis and 17 had non-functioning pituitary adenomas. Among the 38 radiomics parameters obtained from post-contrast T1-weighted images, 10 tissue features that could differentiate the lesions were selected. Machine learning algorithms were performed using three selected parameters; gray level run length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray level co-occurrence entropy. Error matrices were calculated by using the machine learning algorithm and it was seen that support vector machines showed the best performance in distinguishing the two lesion types.

Conclusions

Our analysis reported that support vector machines showed the best performance in distinguishing hypophysitis from non-functioning pituitary adenomas, emphasizing the importance of machine learning in differentiating the two lesions.