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Journal of Oral Biosciences Jun 2024This study aimed to elucidate whether the administration of parathyroid hormone (PTH) results in remodeling- or modeling-based bone formation in different regions of the...
Regional difference in the distribution of alkaline phosphatase, PHOSPHO1, and calcein labeling in the femoral metaphyseal trabeculae in parathyroid hormone-administered mice.
OBJECTIVES
This study aimed to elucidate whether the administration of parathyroid hormone (PTH) results in remodeling- or modeling-based bone formation in different regions of the murine femora, and whether the PTH-driven bone formation would facilitate osteoblastic differentiation into osteocytes.
METHODS
Six-week-old male C57BL/6J mice were employed to examine the distribution of alkaline phosphatase (ALP), PHOSPHO1, podoplanin, and calcein labeling in two distinct long bone regions: the metaphyseal trabeculae close to the chondro-osseous junction (COJ) and those distant from the COJ in three mouse groups, a control group receiving a vehicle (Sham group) and groups receiving hPTH (1-34) twice a day (PTH BID group) or four times a day (PTH QID group) for two weeks.
RESULTS
The Sham group showed PHOSPHO1-reactive mature osteoblasts localized primarily at the COJ, whereas the PTH BID/QID groups exhibited extended lines of PHOSPHO1-reactive osteoblasts even in regions distant from the COJ. The PTH QID group displayed fragmented calcein labeling in trabeculae close to the COJ, whereas continuous labeling was observed in trabeculae distant from the COJ. Osteoblasts tended to express podoplanin and PHOSPHO1 independently in the close and distant regions of the Sham group, while osteoblasts in the PTH-administered groups showed immunoreactivity of podoplanin and PHOSPHO1 together in the close and distant regions.
CONCLUSIONS
Administration of PTH may accelerate remodeling-based bone formation in regions close to the COJ while predominantly inducing modeling-based bone formation in distant regions. PTH appeared to simultaneously facilitate osteoblastic bone mineralization and differentiation into osteocytes in both remodeling- and modeling-based bone formation.
PubMed: 38942193
DOI: 10.1016/j.job.2024.06.007 -
Journal of Oral Biosciences Jun 2024Japanese children have been shown to exhibit decreased masticatory function; however, limited evidence is available regarding the efficacy of certain food items in...
OBJECTIVES
Japanese children have been shown to exhibit decreased masticatory function; however, limited evidence is available regarding the efficacy of certain food items in improving this issue. Therefore, this study examined the effects of chewing hard gummy candy on the masticatory function of Japanese children aged 6-12 years.
METHODS
The study included 26 participants (10 boys and 16 girls; mean age ± standard error = 9.3 ± 0.3 years) who were asked to chew hard gummy candy twice daily for 4 weeks at home. The lip-closing force, occlusal force, and masticatory performance of the participants were recorded before commencement (T1), 4 weeks after commencement (T2), and 4 weeks after completion (T3) of the training. Statistical analyses were performed using the Wilcoxon rank-sum test or the Wilcoxon signed-rank test with Bonferroni correction.
RESULTS
No correlation was observed between masticatory function and sex at T1. The lip-closing and right occlusal forces increased significantly after 4 weeks of exercise, and the effects persisted for another 4 weeks after completion. The masticatory performance also improved after training, although these effects did not persist and deteriorated substantially 4 weeks after completion of the training.
CONCLUSIONS
Habitual mastication training using hard gummy candy markedly enhances masticatory function (e.g., lip-closing force, occlusal force, and masticatory performance) in Japanese children.
PubMed: 38942192
DOI: 10.1016/j.job.2024.06.005 -
Acta Biomaterialia Jun 2024A wide variety of microorganisms have been closely linked to metal corrosion in the form of adherent surface biofilms. Biofilms allow the development and maintenance of... (Review)
Review
A wide variety of microorganisms have been closely linked to metal corrosion in the form of adherent surface biofilms. Biofilms allow the development and maintenance of locally corrosive environments and/or permit direct corrosion including pitting corrosion. The presence of numerous genetically distinct microorganisms in the oral environment poses a threat to the integrity and durability of the surface of metallic prostheses and implants used in routine dentistry. However, the association between oral microorganisms and specific corrosion mechanisms is not clear. It is of practical importance to understand how microbial corrosion occurs and the associated risks to metallic materials in the oral environment. This knowledge is also important for researchers and clinicians who are increasingly concerned about the biological activity of the released corrosion products. Accordingly, the main goal was to comprehensively review the current literature regarding oral microbiologically influenced corrosion (MIC) including characteristics of biofilms and of the oral environment, MIC mechanisms, corrosion behavior in the presence of oral microorganisms and potentially mitigating technologies. Findings included that oral MIC has been ascribed mostly to aggressive metabolites secreted during microbial metabolism (metabolite-mediated MIC). However, from a thermodynamic point of view, extracellular electron transfer mechanisms (EET-MIC) through pili or electron transfer compounds cannot be ruled out. Various MIC mitigating methods have been demonstrated to be effective in short term, but long term evaluations are necessary before clinical applications can be considered. Currently most in-vitro studies fail to simulate the complexity of intraoral physiological conditions which may either reduce or exacerbate corrosion risk, which must be addressed in future studies. STATEMENT OF SIGNIFICANCE: A thorough analysis on literature regarding oral MIC (microbiologically influenced corrosion) of biomedical metallic materials has been carried out, including characteristics of oral environment, MIC mechanisms, corrosion behaviors in the presence of typical oral microorganisms and potential mitigating methods (materials design and surface design). There is currently a lack of mechanistic understanding of oral MIC which is very important not only to corrosion researchers but also to dentists and clinicians. This paper discusses the significance of biofilms from a biocorrosion perspective and summarizes several aspects of MIC mechanisms which could be caused by oral microorganisms. Oral MIC has been closely associated with not only the materials research but also the dental/clinical research fields in this work.
PubMed: 38942189
DOI: 10.1016/j.actbio.2024.06.032 -
European Journal of Pharmaceutics and... Jun 2024Dental caries is one of the most prevalent non-communicable diseases worldwide, mediated by a multispecies biofilm that consists of high levels of acidogenic bacteria...
Dental caries is one of the most prevalent non-communicable diseases worldwide, mediated by a multispecies biofilm that consists of high levels of acidogenic bacteria which ferment sugar to acid and cause teeth demineralization. Current treatment practice remains insufficient in addressing 1) rapid clearance of therapeutic agents from the oral environment 2) destroying bacteria that contribute to the healthy oral microbiome. In addition, increasing concerns over antibiotic resistance calls for innovative alternatives. In this study, we developed a pH responsive nano-carrier for delivery of polycationic silver nanoparticles. Branched-PEI capped silver nanoparticles (BPEI-AgNPs) were encapsulated in a tannic acid - Fe (III) complex-modified poly(D,L-lactic-co-glycolic acid) (PLGA) particle (Fe(III)-TA/PLGA@BPEI-AgNPs) to enhance binding to the plaque biofilm and demonstrate "intelligence" by releasing BPEI-AgNPs under acidic conditions that promote dental caries The constructed Fe(III)-TA/PLGA@BPEI-AgNPs (intelligent particles - IPs) exhibited significant binding to an axenic S. mutans biofilm grown on hydroxyapatite. Ag ions were released faster from the IPs at pH 4.0 (cariogenic pH) compared to pH 7.4. The antibiofilm results indicated that IPs can significantly reduce S. mutans biofilm volume and viability under acidic conditions. Cytotoxicity on differentiated Caco-2 cells and human gingival fibroblasts indicated that IPs were not cytotoxic. These findings demonstrate great potential of IPs in the treatment of dental caries.
PubMed: 38942176
DOI: 10.1016/j.ejpb.2024.114374 -
European Journal of Pharmaceutics and... Jun 2024Alzheimer's disease (ALZ) is a neurological disorder characterized by cognitive decline. Rivastigmine (RV), an acetylcholinesterase inhibitor, is commonly used to treat...
Implantable trilayer microneedle transdermal delivery system to enhance bioavailability and brain delivery of rivastigmine for Alzheimer treatment: A proof-of-concept study.
Alzheimer's disease (ALZ) is a neurological disorder characterized by cognitive decline. Rivastigmine (RV), an acetylcholinesterase inhibitor, is commonly used to treat ALZ. Unfortunately, RV is availablein capsule form, which is associated with low drug bioavailability, and in patch form, which can lead to skin irritation upon repeated use. This study successfully fabricated a trilayer dissolving microneedle (TDMN) containing RV with adequate mechanical strength by using the molding method. In vitro release and ex vivo permeation showed that the release and permeation of RV were significantly sustained compared to control without PCL. The release and permeation percentages were 91.34 ± 11.39 % and 13.76 ± 1.49 μg/cm, respectively. In addition, the concentration of RV in plasma and brain after 168 h was measured to be 0.44 ± 0.09 µg/mL and 1.23 ± 0.26 µg/g, respectively, which reached the minimum concentration to inhibit AcHE and BuChe. Pharmacokinetic testing revealed higher AUC values after administration of TDMN, indicating better bioavailability, and RV concentrations in the brain were found to be twice as high as those achieved with oral administration. This study suggests TDMN may enhance the bioavailability and brain delivery of RV.
PubMed: 38942175
DOI: 10.1016/j.ejpb.2024.114382 -
Food and Chemical Toxicology : An... Jun 2024The human gut microbiome plays a crucial role in immune function. The synbiotic consortium or Defined Microbial Assemblage™ (DMA™) Medical Food product, SBD121,...
The human gut microbiome plays a crucial role in immune function. The synbiotic consortium or Defined Microbial Assemblage™ (DMA™) Medical Food product, SBD121, consisting of probiotic microbes and prebiotic fibers was designed for the clinical dietary management of rheumatoid arthritis. A 28-day repeated administration study was performed to evaluate the oral toxicity of SBD121 in male and female rats (age/weight at study start: 60 days/ 156-264 grams) administered levels of 0, 4.96 x 10, 2.48 x 10, or 4.96 x 10 colony forming units (CFU)/kg-bw. No treatment related changes in ophthalmological effects, mortality, morbidity, general health and clinical observations, urinalysis, hematology, serum chemistry, absolute or relative organ weights, gross necropsy, or histopathology. A significant decrease in body weight was reported in females in the low and high-concentration groups, which corresponded in part with a significant decrease in food consumption. Results of the functional observation battery indicated front grip strength was significantly greater in the high-concentration males compared to the controls; however, this effect was not considered adverse. Based on these findings, the administration of the Medical Food SBD121 to male and female rats has a no-observable adverse effect level (NOAEL) at the highest level tested of 4.96 x 10 CFU/kg-bw.
PubMed: 38942165
DOI: 10.1016/j.fct.2024.114839 -
Radiotherapy and Oncology : Journal of... Jun 2024In the last decades FDG-PET/CT is increasingly used in combination with the standard diagnostic modalities (MRI + US-FNA) to identify residual neck disease (RND)...
PURPOSE
In the last decades FDG-PET/CT is increasingly used in combination with the standard diagnostic modalities (MRI + US-FNA) to identify residual neck disease (RND) after (chemo)radiotherapy for head-and-neck squamous cell carcinoma (HNSCC). The purpose of the current study is to identify the impact of increasing use of FDG-PET/CT on the accuracy of patient selection for salvage neck dissection (SND).
MATERIALS AND METHODS
Between 2008 and 2022, 908 consecutive patients with node-positive HNSCC were treated with (chemo)radiotherapy in our institution.
PRIMARY ENDPOINT
positive predictive value (PPV) of FDG-PET/CT for pathologic-confirmed RND (pRND) after SND, compared to the standard of care; MRI + US-FNA. Secondary endpoints: oncologic outcomes.
RESULTS
Of the entire group, 130 patients (14 %) received SND. Of them only 53 patients (41 %) had pRND at the SND-specimens. The PPV of FDG-PET/CT for the detection of pRND was considerably better, compared to MRI + US-FNA; 89 % and 65 %, respectively. If FDG-PET/CT showed metabolic CR, these patients did not undergo SND. The NPV was 97.5 %, as only 2.5 % of these patients developed delayed regional failure. FDG-PET/CT considerably improved the accuracy of patient selection for SND, as significantly more patients treated in the second period, compared to first period of the study (n = 454 each) still had vital tumor at SND-specimen (53 % and 31 %, p = 0.008). Regional recurrence free-survival, DFS, OS and HNSCC-death were significantly worse in patients with pRND (p < 0.05) CONCLUSIONS: Incorporating FDG-PET/CT into the diagnostic pathway for the response evaluation after (chemo)radiotherapy significantly improved the accuracy of patient selection for SND and spared considerable number of patients (>20 %) from unnecessary SND. For patients with metabolic CR, SND can safely be omitted while for patients with no metabolic CR, SND is strongly advocated.
PubMed: 38942119
DOI: 10.1016/j.radonc.2024.110407 -
Journal of Dentistry Jun 2024This study evaluated the clinical performance of Class II restorations made with flowable bulk-fill base versus conventional layering ORMOCER-based restorative material...
OBJECTIVE
This study evaluated the clinical performance of Class II restorations made with flowable bulk-fill base versus conventional layering ORMOCER-based restorative material in a split-mouth randomized clinical trial.
METHODS
Thirty patients received two class II restorations (n=60) performed with different strategies. All preparations received the application of the universal self-etching adhesive system according to the manufacturer's recommendation, followed by the placement of a sectional matrix, wooden wedge, and separation ring. The first restoration was performed using 4 mm of flowable bulk-fill material covered by 2 mm of conventional viscosity restorative material (Bulk-fill technique). The second restoration was performed only with the conventional viscosity material, with a maximum of 2 mm thick increments, up to fill the cavity (Layering technique). After occlusal adjustment, the same polishing system was used for all restorations. Evaluations using the FDI criteria were conducted after 7 days, 12, and 24 months. Data were analyzed with the Fisher's Exact test (α=0.05).
RESULTS
From 30 participants, 24 attended the 24-month recall, and 48 restorations were evaluated. All restorations received acceptable overall scores for esthetic and biological properties after this period, while only 6.66% of the restorations exhibited unacceptable overall scores for the functional properties in both groups. No significant differences between the tested restorative materials and techniques were found for each FDI criterion assessed. The success rate after 2 years was 93.33% for both groups.
CONCLUSION
Both restorative materials exhibited good clinical performance for the parameters analyzed with no differences between them after 24-month follow-up.
CLINICAL RELEVANCE
Flowable bulk-fill ORMOCER-based material is a suitable alternative for direct Class II restorations, providing good clinical outcomes and simplifying the restorative procedure.
CLINICAL TRIAL REGISTRATION NUMBER
RBR-6mvp9w.
PubMed: 38942111
DOI: 10.1016/j.jdent.2024.105154 -
Behavioural Brain Research Jun 2024The central route of streptozotocin (STZ) administration has been introduced as a rat model of sporadic Alzheimer's disease (AD). Curcumin was suggested to possess...
The central route of streptozotocin (STZ) administration has been introduced as a rat model of sporadic Alzheimer's disease (AD). Curcumin was suggested to possess possible neuroprotective effects, which may be profitable in AD. However, the low bioavailability of curcumin hinders its beneficial effects in clinical studies. Earlier studies suggested that a bovine serum albumin-based nanocurcumin, produces superior neuroprotective effects compared to natural curcumin. In the present study, the protective effect of nanocurcumin in rat model of central STZ induced memory impairment was assessed. In addition, due to the importance of the hippocampus in memory, the amounts of hippocampal active caspase-3, Akt, and CaMKII-α were evaluated. Adult male Wistar rats weighing 250-300g were used. STZ (icv) was injected during days 1 and 3 (3mg/kg in divided), and nanocurcumin or curcumin 50mg/kg/oral gavage was administered daily during days 4-14. Morris water maze training was performed on days 15-17, and the retention memory test was achieved on the 18th day. Following memory assessment, the rats were sacrificed and the hippocampi were used to assess caspase-3 cleavage, Akt, and CaMKII-α signaling. The findings revealed that nanocurcumin ingestion (but not natural curcumin) in the dose of 50mg/kg was capable to prevent the impairment of water maze learning and memory induced by central STZ. Molecular assessments indicated that STZ treatment increased the caspase-3 cleavage in the hippocampus while deactivating Akt and CaMKII-α. Nanocurcumin reduced caspase-3 cleavage to a non-significant level compared to control group and restored Akt and CaMKII-α within the hippocampus while natural curcumin exerted no significant effect. These findings might suggest that nanocurcumin can restore memory deficit, hippocampal apoptosis as well as Akt and CaMKII-α signaling disruption associated with brain insulin resistance.
PubMed: 38942084
DOI: 10.1016/j.bbr.2024.115129 -
Annales Pharmaceutiques Francaises Jun 2024Edaravone (EDR) is an effective neuroprotective agent in various neurological diseases; however, its use is restricted due to poor oral absorption. Bile salts are known...
OBJECTIVES
Edaravone (EDR) is an effective neuroprotective agent in various neurological diseases; however, its use is restricted due to poor oral absorption. Bile salts are known for improving solubility and inhibiting drug crystallization in supersaturated conditions of the gastrointestinal tract (GIT). In our previous work, we prepared coamorphous dispersion (COAM) of EDR with sodium taurocholate (NaTC) using spray drying. The optimized EDR COAM exhibited superior in vitro performance compared to plain EDR. EDR is well absorbed in fasted-over-fed conditions.
METHODS
The present work, we conducted a pharmacokinetic study for EDR and EDR COAM in fasted and fed conditions to check effect of food on its oral absorption. The LC-MS/MS-based method was developed and validated to determine the amount of EDR in plasma.
RESULTS
The results suggested that EDR COAM did not show a significant difference in C (p=0.3544) and AUC (p=0.1696) of fasted and fed states. On the other hand, plain EDR showed 2-fold and 3-fold reduced C (p<0.0001) and AUC (p=0.0094) in the fed condition, respectively. The C and AUC of EDR COAM were improved in fasted (AUC:2.56-fold) and fed states (AUC: 5.74-fold) than plain EDR, suggesting better oral absorption of COAM than crystalline EDR without having the effect of food.
CONCLUSIONS
The unique structural attributes of NaTC had the potential to inhibit the recrystallization of EDR in GIT, while concurrently reducing the impact of food on the oral absorption of EDR.
PubMed: 38942078
DOI: 10.1016/j.pharma.2024.06.005