Pectin and Mucin Enhance the Bioadhesion of Drug Loaded Nanofibrillated Cellulose Films

Purpose

Bioadhesion is an important property of biological membranes, that can be utilized in pharmaceutical and biomedical applications. In this study, we have fabricated mucoadhesive drug releasing films with bio-based, non-toxic and biodegradable polymers that do not require chemical modifications.

Methods

Nanofibrillar cellulose and anionic type nanofibrillar cellulose were used as film forming materials with known mucoadhesive components mucin, pectin and chitosan as functional bioadhesion enhancers. Different polymer combinations were investigated to study the adhesiveness, solid state characteristics, film morphology, swelling, mechanical properties, drug release with the model compound metronidazole and in vitro cytotoxicity using TR146 cells to model buccal epithelium.

Results

SEM revealed lamellar structures within the films, which had a thickness ranging 40–240 μm depending on the film polymer composition. All bioadhesive components were non-toxic and showed high adhesiveness. Rapid drug release was observed, as 60–80% of the total amount of metronidazole was released in 30 min depending on the film formulation.

Conclusions

The liquid molding used was a straightforward and simple method to produce drug releasing highly mucoadhesive films, which could be utilized in treating local oral diseases, such as periodontitis. All materials used were natural biodegradable polymers from renewable sources, which are generally regarded as safe.

     

Incidence of persistent renal dysfunction after contrast enhanced coronary CT angiography in patients with suspected coronary artery disease

Contrast-induced nephropathy (CIN) is a potentially serious complication of contrast agents used in computed tomography angiography (CTA). The aim of this study was to evaluate whether persistent renal dysfunction occurs in patients undergoing coronary CTA for suspected stable coronary artery disease (CAD). From a cohort of 957 patients undergone coronary CTA, we identified 402 patients with plasma creatinine levels collected before and within 6 months after CTA. According to the definition of CIN, patients with a ≥25?% increase in plasma creatinine after CTA were evaluated. The post-CTA measurements in 402 patients (195 men, age 62.9?±?9.3 years) were performed at a median of 99 days after CTA. On average, there was no change in plasma creatinine level between the pre- and post-CTA measurements (75.8?±?16.0 and 75.7?±?16.4 µmol/L, respectively; P?=?0.63) but both increases and decreases were commonly detected. Fourteen (3.5?%) patients had a ≥25?% increase in plasma creatinine levels after CTA. A more detailed evaluation of these patients revealed that in 4 patients the increase was explained by other morbidities, whereas in 9 patients the creatinine level returned to the previous levels at later follow-up (median time to normalization: 311 days). Only in 1 (0.2?%) remaining patient, there was a persistent increase in plasma creatinine level, possibly related to the iodine contrast agent exposure. Alterations in plasma creatinine concentration occur frequently. Persistent renal dysfunction attributable to iodine contrast agent exposure is rare in patients referred to coronary CTA for suspected CAD.     

Changes in cardiovascular autonomic regulation among elderly subjects: follow-up of sixteen years

BACKGROUND: Previous cross-sectional studies have suggested that cardiac autonomic regulation, measured as heart rate (HR) variability, is altered upon ageing, and that altered HR variability may predict mortality. However, there are no longitudinal follow-up reports of the changes of HR dynamics in elderly subjects. AIM & METHOD: This study was designed to examine the longitudinal changes in the spectral, fractal, and complexity measures of HR variability in a random sample of 41 elderly subjects (mean age 69+/-4 years), who underwent repeated 24-hour Holter recordings at the baseline and after 16 years' follow-up. Several cardiovascular risk factors were determined at the baseline. RESULTS: A time-domain index, standard deviation of N-N intervals (SDNN) (142+/-34 msec versus 133+/-50 msec, not significant (NS)), and the high frequency spectral component of HR variability (219+/-222 msec(2)versus 268+/-287 msec(2), NS) did not change during the follow-up. The low frequency power (LF) of HR variability decreased from 678+/-654 msec(2) to 436+/-651 msec(2) (P<0.01). Among the fractal HR variability indexes, the power-law slope (ss) (-1.31+/-0.20 versus -1.47+/-0.21, P<0.001) and the short-term fractal exponent a1 (1.16+/-0.19 versus 1.06+/-0.18, P<0.01) decreased significantly. Approximate entropy remained unchanged. CONCLUSIONS: The magnitude of total HR variability and the respiratory vagal modulation of HR do not change over time in the elderly. However, the spectral and fractal characteristics of HR behavior still undergo alterations upon ageing.     

The microenvironment of proliferative diabetic retinopathy supports lymphatic neovascularization

Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication characterized by pathological angiogenesis. Several retinopathy animal models have been developed to study the disease mechanisms and putative targets. However, knowledge on the human proliferative disease remains incomplete, relying on steady‐state results from thin histological neovascular tissue sections and vitreous samples. New translational models are thus required to comprehensively understand the disease pathophysiology and develop improved therapeutic interventions. We describe here a clinically relevant model, whereby the native multicellular PDR landscape and neo(fibro)vascular processes can be analysed ex vivo and related to clinical data. As characterized by three‐dimensional whole‐mount immunofluorescence and electron microscopy, heterogeneity in patient‐derived PDR neovascular tissues included discontinuous capillaries coupled with aberrantly differentiated, lymphatic‐like and tortuous endothelia. Spatially confined apoptosis and proliferation coexisted with inflammatory cell infiltration and unique vascular islet formation. Ex vivo‐cultured explants retained multicellularity, islet patterning and capillary or fibrotic outgrowth in response to vitreoretinal factors. Strikingly, PDR neovascular tissues, whose matched vitreous samples enhanced lymphatic endothelial cell sprouting, contained lymphatic‐like capillaries in vivo and developed Prox1⁺ capillaries and sprouts with lymphatic endothelial ultrastructures ex vivo. Among multiple vitreal components, vascular endothelial growth factor C was one factor found at lymphatic endothelium‐activating concentrations. These results indicate that the ischaemia‐induced and inflammation‐induced human PDR microenvironment supports pathological neolymphovascularization, providing a new concept regarding PDR mechanisms and targeting options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Endoscopic papillectomy,single-centre experience

Background

Endoscopic removal of benign tumours of papilla is increasing. Our aim was to evaluate the outcome of endoscopic resection of papillary tumours.

Methods

In the years 2000–2012, 61 papillectomies were performed in Helsinki University Central Hospital. The cases were analysed retrospectively.

Results

There were 35 patients with benign tumour of papilla without familial adenomatous polyposis (FAP), 16 patients with FAP and 10 patients with ampullary cancer. Jaundice and bile duct dilation were risk factors for malignancy (p < 0.001). In benign tumours, the recurrence rate was 25.5 %. In 5/51 benign tumour cases (9.8 %), a pancreaticoduodenectomy was performed. The remaining cases were treated endoscopically. Neither tumour size, resection in one piece or piecemeal technique, nor coagulation of resection margins had an effect on the development of residual tumour. The total complication rate was 24.6 %. Pancreatitis developed in six patients (9.8 %, 3 mild and 3 moderate). In benign tumour cases, pancreatic stent decreased pancreatitis rate (p = 0.045). In cases where only a pancreatic sphincterotomy was performed, the risk of pancreatitis was high 4/7 (57 %). Bleeding was the most common complication (18 %). Only one patient was operated due to complication, a post-papillectomy bleeding. In six out of seven non-operated cancer patients, the disease progressed.

Conclusion

Endoscopic papillectomy is an effective procedure for treating benign papillary tumours. Jaundice and bile duct dilation are more common in malignant tumours. Pancreatic stent decreases the risk of post-papillectomy pancreatitis. Pancreatic sphincterotomy without stenting carries a high risk of pancreatitis. For papillary cancer, surgery is recommended.     

Pediatric solid organ transplantation and osteoporosis: a descriptive study on bone histomorphometric findings

Background

Organ transplantation may lead to secondary osteoporosis in children. This study characterized bone histomorphometric findings in pediatric solid organ transplant recipients who were assessed for suspected secondary osteoporosis.

Methods

Iliac crest biopsies were obtained from 19 children (7.6–18.8 years, 11 male) who had undergone kidney (n?=?6), liver (n?=?9), or heart (n?=?4) transplantation a median 4.6 years (range 0.6–16.3 years) earlier. All patients had received oral glucocorticoids at the time of the biopsy.

Results

Of the 19 patients, 21 % had sustained peripheral fractures and 58 % vertebral compression fractures. Nine children (47 %) had a lumbar spine BMD Z-score below ?2.0. Histomorphometric analyses showed low trabecular bone volume (< ?1.0 SD) in 6 children (32 %) and decreased trabecular thickness in 14 children (74 %). Seven children (37 %) had high bone turnover at biopsy, and low turnover was found in 6 children (32 %), 1 of whom had adynamic bone disease.

Conclusions

There was a great heterogeneity in the histological findings in different transplant groups, and the results were unpredictable using non-invasive methods. The observed changes in bone quality (i.e. abnormal turnover rate, thin trabeculae) rather than the actual loss of trabecular bone, might explain the increased fracture risk in pediatric solid organ transplant recipients.