Enhancing Guided Tissue Regeneration of Periodontal Defects by Using a Novel Perforated Barrier Membrane

Background: The present study was designed to determine whether exclusion of the gingival connective tissue (CT) and periosteum with contained stem cells has a positive or negative effect on periodontal regeneration by comparing the use of a novel modified perforated collagen membrane with a traditional cell occlusive barrier membrane. Methods: Twenty non‐smoking patients with severe chronic periodontitis were included in the study. Single deep intrabony defects from each of the patients were randomly divided into two groups, as follows: occlusive bovine collagen membranes (OM control group, 10 sites) and modified perforated bovine collagen membranes (MPM test group, 10 sites). Plaque index, gingival index, probing depth (PD), clinical attachment level (CAL), defect base level (DBL), and crestal bone level (CBL) were measured at baseline and were reassessed at 6 and 9 months after therapy to evaluate the quantitative changes in the defect. Results: At 6‐ and 9‐month observation periods, the MPM‐treated sites showed a statistically significant improvement in PD reduction and CAL gain compared with the OM control group. DBL was significantly reduced with no significant difference between the two groups at 6‐ and 9‐month observation periods. CBL was significantly higher in the MPM group when compared with that of the OM group at both observation periods. The postoperative differences between the two groups were 2 and 1.7 mm at 6 and 9 months, respectively, in favor of the MPM‐treated sites. Conclusions: The present study demonstrated enhanced clinical outcomes when using novel MPMs compared to OMs in guided tissue regeneration procedures. These results may be affected by the penetration of gingival CT contained stem cells and periosteal cells and their differentiation into components of the attachment apparatus.     

Doxycycline‐Loaded β‐Tricalcium Phosphate Release Following EDTA Root Surface Etching Improved the Clinical Outcomes in Chronic Periodontitis: An In Vivo Study

Background: The main objective of the present study is to quantify doxycycline (DOX) release from β‐tricalcium phosphate (β‐TCP) after EDTA root surface treatment. Methods: Thirty systemically healthy patients with ≥1 paired contralateral interproximal intrabony defect ≥4 mm deep along with an interproximal probing depth ≥6 mm and clinical attachment level ≥4 mm were randomized into two groups. Group 1 (G1) consisted of sites treated with open flap debridement followed by placement of DOX blended with β‐TCP (DOX‐β‐TCP), whereas group 2 (G2) sites were treated with flap surgery followed by the placement of DOX blended with β‐TCP after EDTA etching of the exposed root surfaces (DOX‐β‐TCP + EDTA). Samples of gingival crevicular fluid (GCF) were obtained 1, 3, 7, 14, and 21 days after surgery. Quantitative measurements of DOX were taken with high‐performance liquid chromatography. Clinical evaluation and follow‐up for 6 months were performed. Results: At 21 days, the DOX‐β‐TCP + EDTA–treated group showed a 194.7 µg/mL value. The DOX‐β‐TCP + EDTA–treated group retained more DOX during the periods of 3, 7, 10, 14, and 21 days than the DOX‐β‐TCP–treated group. Six months after therapy, DOX‐β‐TCP + EDTA–treated sites showed more significant clinical improvements compared to DOX‐β‐TCP–treated sites (P ≤ 0.05). Conclusions: EDTA root surface etching enhances DOX availability in the GCF following its release from β‐TCP as a drug carrier.     

“Tau Protein Targeting Via Radioiodinated Azure A For Brain Theranostics: Radiolabeling,Molecular Docking,in vitro And in vivo Biological Evaluation”

Azure-A is one of the phenothiazines (PTZs) derivatives which for decades have been used as antipsychotic drugs due to good lipophilic characteristics which enable them to pass through the blood brain barrier (BBB), besides the important property of enabeling investigation of the pathological forms of aggregated tau protein found in the neurons of the central nervous system. Radioiodination of Azure-A was carried out via an electrophilic substitution reaction using chloramine-T as oxidizing agent. The influence of various reaction parameters and conditions on radioiodination efficiency was investigated, and a high radiochemical yield of 92.07 ± 0.9 % was obtained. An in vitro cytotoxicity study of iodinated Azure-A on three cell lines (HCT-116, human colon carcinoma cell line; Hep-G2, liver carcinoma cell line and HFB-4, normal human melanocytes) was carried out, and the data revealed that ioiodinated Azure A has no to very low toxic effect. The in vivo biodistribution study of ¹³¹I-Azure A showed a high brain uptake of 6.15 ± 0.09 % injected dose/g tissue organ at 30 minutes post-injection, and its retention in brain remained high up to 2 hours, whereas the clearance from the body appeared to proceed via the renal system. The experimental data were confirmed by the molecular docking studies to predict the effect of radioiodination on the binding affinity of the parent molecule (Azure A) to tau paired helical filaments (PHFs). Both ligands showed better binding to S2 and S3 pockets of (PHFs). Consequently, radioiodinated Azure A seems to be a good candidate as an imaging agent for taupathies such as Alzheimer's disease, chronic traumatic encephalopathy, and corticobasal degeneration. Furthermore, it could be a very potent theranostics agent for brain tumors.     

Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Diagnostic Tool in the Assessment of Tumour Angiogenesis in Urinary Bladder Cancer

PurposeThe aim of study is to assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and correlation with tumour angiogenesis in evaluation of urinary bladder cancer.Material and MethodsThe study included 81 patients with recent presumed diagnosis of bladder tumour or who came for follow up after management of histopathologically proven bladder cancer. All had DCE-MRI with time–signal intensity curve. The radiologic results then correlated with the histopathologic results using both haematoxylin and eosin stain and immuno-histochemical staining for localization and evaluation of CD34 immunoreactivity as a detector for the microvessel density (MVD) and tumour angiogenesis.ResultsSeventy-one cases were pathologically proven to be malignant: 41 cases (58%) showed type III time–signal intensity curve (descending); 22 cases (31%) showed type II (plateau); and 8 cases (11%) showed type I (ascending) curve. The sensitivity of DCE-MRI in stage T1 bladder tumour was 80%; in stage T2, it was (90.9%); and in stage T3, it was (96.9%). Overall accuracy of DCE-MRI in tumour staging was 89.5% and P = .001 (significant). Values more than the cutoff value = 76.13 MVD are cystitis with sensitivity (90%), specificity (91%), and P value is .001, which is statistically highly significant.ConclusionThere is a strong positive association between DCE-MRI (staging and washout slope of the time–signal intensity curve) with histopathologic grade, tumour stage, and MVD in bladder cancer. So, DCE-MRI can be used as reliable technique in preoperative predictions of tumour behavior and affect the planning of antiangiogenetic therapy.     

Subacromial injection of autologous platelet-rich plasma versus corticosteroid for the treatment of symptomatic partial rotator cuff tears

Objective

Rotator cuff tears are one of the most common causes of chronic shoulder pain and disability. They significantly affect the quality of life. Reduced pain and improved function are the goals of conventional therapy, which includes relative rest, pain therapy, physical therapy, corticosteroid injections and surgical intervention. Tendons have a relative avascular nature; hence, their regenerative potential is limited. There is some clinical evidence that the application of autologous platelets may help to revascularize the area of injury in rotator cuff pathologies.

Patients and methods

This prospective randomized controlled study was done to evaluate the results of subacromial injection of platelet-rich plasma (PRP) versus corticosteroid injection therapy in 40 patients with symptomatic partial rotator cuff tears. All patients were assessed before injection, 6 weeks, 3 and 6 months after injection, using the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), the Constant–Murley Score (CMS), the Simple Shoulder Test (SST) and a Visual Analog Scale (VAS) for pain. An MRI was performed before and 6 months after the injection for all the included patients and was graded on 0–5 scale.

Results

Both injection groups showed statistically significantly better clinical outcomes over time compared with those before injection. There was a statistically significant difference between RPP group and corticosteroid group 12 weeks after injection, regarding VAS, ASES, CMS and SST in favor of the RPP group. MRI showed an overall slight nonsignificant improvement in grades of tendinopathy/tear in both groups, however, without statistically significant differences between the two groups.

Conclusion

PRP injections showed earlier better results as compared to corticosteroid injections, although statistically significant better results after 6 months could not be found. Therefore, subacromial RPP injection could be considered as a good alternative to corticosteroid injection, especially in patients with a contraindication to corticosteroid administration.

Level of evidence

II.

     

Chitosan-Gelatin Hydrogel Crosslinked With Oxidized Sucrose for the Ocular Delivery of Timolol Maleate

Ocular hypertension due to increased intraocular pressure is a major risk factor for the development of glaucoma. Rapid clearance and low ocular bioavailability are drawbacks of conventional ocular treatments. This requires frequent and long-term application of antiglaucoma drugs which in turn cause local side effects and are a major cause of therapeutic failure due to loss of persistence in using glaucoma therapy. In this study, a semisynthetic, biocompatible, oxidized sucrose crosslinker was developed and used in the formulation of chitosan-gelatin hydrogel for the sustained release of timolol to control ocular hypertension. The swelling properties of the hydrogel showed a strong relationship with the oxidized sucrose concentration. Mucoadhesive properties of the hydrogel were studied and the in vitro release profiles demonstrated that crosslinking with oxidized sucrose reduced the release rate of the entrapped timolol. The results of both in vitro and in vivo studies supported that the formulated hydrogel maintained the release and in turn the efficacy of timolol for a longer period of time compared to the conventional eye drops. This is expected to reduce the frequency of drug application onto the eye surface and in turn enhances patients’ convenience. In conclusion, the developed formulation represents a promising platform for an effective and compliant treatment of ocular hypertension.