Interleukin-10 signaling in somatosensory neurons controls CCL2 release and inflammatory response.

Appropriate regulation of the inflammatory response is essential for survival. Interleukin-10 (IL-10), a well-known anti-inflammatory cytokine, plays a major role in controlling inflammation. In addition to immune cells, we previously demonstrated that the IL-10 receptor (IL-10R1) is expressed in dorsal root ganglion sensory neurons. There is emerging evidence that these sensory neurons contribute to immunoregulation, and we hypothesized that IL-10 signaling in dorsal root ganglion (DRG) neurons facilitates the regulation of the inflammatory response. We showed that mice that lack IL-10R1 specifically on advillin-positive neurons have exaggerated blood nitric oxide levels, spinal microglia activation, and cytokine upregulation in the spinal cord, liver, and gut compared to wild-type (WT) counterparts in response to systemic lipopolysaccharide (LPS) injection. Lack of IL-10R1 in DRG and trigeminal ganglion (TG) neurons also increased circulating and DRG levels of proinflammatory C-C motif chemokine ligand 2 (CCL2). Interestingly, analysis of published scRNA-seq data revealed that Ccl2 and Il10ra are expressed by similar types of DRG neurons; nonpeptidergic P2X purinoceptor (P2X3R + ) neurons. In primary cultures of DRG neurons, we demonstrated that IL-10R1 inhibits the production of CCL2, but not that of the neuropeptides substance P and calcitonin-gene related peptide (CGRP). Furthermore, our data indicate that ablation of Transient receptor potential vanilloid (TRPV)1 + neurons does not impact the regulation of CCL2 production by IL-10. In conclusion, we showed that IL-10 binds to its receptor on sensory neurons to downregulate CCL2 and contribute to immunoregulation by reducing the attraction of immune cells by DRG neuron-derived CCL2. This is the first evidence that anti-inflammatory cytokines limit inflammation through direct binding to receptors on sensory neurons. Our data also add to the growing literature that sensory neurons have immunomodulatory functions.

Escherichia coli Cellular Activity and Frontal Trizonal Evaluation of Microspace Between Implants and Abutments Under Calibrated Cyclic Stress.

AIM: To evaluate microspace and microleakage between implant and abutments subjected to pre- and post-calibrated cyclic stress. MATERIALS AND METHODS: Twelve screw-retained implant prostheses with BioHPP polyetheretherketone (PEEK) abutment (Noris Dental Implant System Ltd., Nesher, Israel) (Group I) and 12 screw-retained implant prostheses with computer-assisted design/computer-assisted manufacturing (CAD/CAM) milled zirconia abutment (DentGallop, Houston, TX, USA) (Group II) were connected to their respective implant, and the prosthetic screw was torqued to 30N/cm (Noris). The microspace was evaluated using scanning electron microscopy (SEM; TeScan, Brno, Czech Republic). Twenty-four samples were then induced to cyclic stress (Lokesh Industries, Pune, India) simulating 180 days duration of oral stress. The microspaces (Group IA and Group IIB) were measured post-cyclic stress. Group I and II were again renamed into Group Ia and Group IIb for microbial study. Both implant assemblies were immersed in fresh soybean casein digest broth (SCDB) (Himedia, Mumbai, India) and subsequently inoculated with 1.0µL E. coli suspension (Himedia) at the open end and incubated at 37ºC for seven days. After the incubation period, cellular activity was determined by the spread plate method, and total colony-forming units (CFU) were calculated. The results were evaluated using independent T and Mann-Whitney tests. RESULT: Average and microspace at the implant-abutment junction of Group I samples in the front right was 12.98µm, center 13.76µm, front left 13.22µm, and in Group II samples, the front right was 18.52µm, center 17.84µm, front left 18.58µm.After being subjected to cyclic loading, the mean levels of the vertical microgap for Group IA samples were: in the front right region 10.37µm, in the center 9.34µm, in the front left 10.51µm and in Group IIB samples front right was 14.59µm, center 13.39µm, front left 13.8µm. Independent t-tests showed insignificant differences between the two groups. The median value of microbial leakage of Group Ia samples after cyclic loading was 30 x 103 CFU/ml, and Group IIb samples were 42 x 103 CFU/ml and were significant. CONCLUSION: There was minimal variation in the mean microspace between the BioHPP PEEK abutment and CAD/CAM milled zirconia abutment, and it was insignificant before and after cyclic stress. BioHPP PEEK abutment-titanium implant interfaces showed significantly decreased microbial leakage than CAD/CAM milled zirconia abutment-titanium implant interfaces after cyclic stress.

Graftless Immediate Dual Implant Anatomic Placement With Immediate Provisional Passive Loading and Definitive Hybrid Crown for the Restoration of Mandibular Molar: A Clinical Report.

Immediate implant placement is well-known science and treatment in implant dentistry. It is a multitasking treatment consisting of surgical, prosthodontic, and periodontal aspects, implemented to obtain long-term clinically esthetic and functioning prosthesis. Immediate placement enables clinicians to reduce the number of surgical steps and shorter treatment duration. It has become a standard surgical protocol in modern implant practice. According to existing literature, dual implant placement can be done to avoid any cantilever effect in a single implant and to distribute masticatory forces. This clinical report describes the extraction of an infected mandibular right first molar, (46, Federation Dentaire Internationale) followed by immediate dual placement of dental implants in the rinsed and cleansed sockets. The tooth was atraumatically extracted from the socket, and the latter was prepared to the required depth, and endosseous implants were placed in both the mesial and distal sockets. This atraumatic graft-free operating technique and immediate placement resulted in the preservation of hard and soft tissues. It also increased the patient's comfort, acceptance, and satisfaction due to immediate loading with a provisional removable prosthesis. This was later replaced with a dual screw-retained hybrid implant crown.

Treatment Intricacies in Mandibular Implant-Supported Rehabilitation of a Patient With Down Syndrome: A Clinical Report.

Edentulism is considered a poor health condition and may compromise the quality of life. Prosthodontic replacement of missing teeth results in significant improvement of oral functions. Treating a patient with Down syndrome can pose clinical challenges in handling the emotional aspect as well as in rendering treatment. Careful oral analysis and diagnosis of the existing conditions in such patients will enable and pave the way for clinically acceptable treatment results. This clinical report describes the challenges encountered in the prosthodontic management of an edentulous young patient with Down syndrome.

Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects.

Cisplatin is a potent chemotherapeutic drug that is widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, in particular nephrotoxicity and chemotherapy-induced peripheral neuropathy. Thus, there is an urgent medical need to identify novel strategies that limit cisplatin-induced toxicity. In the present study, we show that the FDA-approved adenosine A2A receptor antagonist istradefylline (KW6002) protected from cisplatin-induced nephrotoxicity and neuropathic pain in mice with or without tumors. Moreover, we also demonstrate that the antitumoral properties of cisplatin were not altered by istradefylline in tumor-bearing mice and could even be potentiated. Altogether, our results support the use of istradefylline as a valuable preventive approach for the clinical management of patients undergoing cisplatin treatment.

Surface Characteristics and Bioactivity of Zirconia (Y-TZP) with Different Surface Treatments.

BACKGROUND: Zirconia being a bio-inert material needs to be surface treated to render it more bioactive and enhance its osseointegration potential. However, bioactivity studies focusing on the ability of sandblasting and ultraviolet photofunctionalization (UVP) surface treatments in inducing apatite precipitation using simulated body fluid (SBF) are lacking. AIM: The aim of the study was to comparatively evaluate the effect of two different surface treatments-sandblasting with 50 µm alumina and UVP with ultraviolet C (UVC) light on the bioactivity of zirconia. MATERIALS AND METHODS: A total of 33 discs with dimensions 10 mm × 2 mm were obtained from zirconia blanks (Amann Girrbach, Koblach, Austria) and randomly divided into three groups (n = 11), namely Group I (untreated), Group II (sandblasted), and Group III (UVP). Surface characteristics of representative test samples were analyzed using X-ray diffraction (XRD), atomic force microscopy (AFM), contact angle goniometry, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX), to assess type of crystal phase of zirconia, surface roughness, wettability, surface topography, and elemental composition, respectively. SBF was prepared and calcium content in SBF (Ca-SBF) was determined using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Data were analyzed by one-way analysis of variance (ANOVA), post hoc Tukey honestly significant difference (HSD), and Student's t test for statistical significance (P < 0.05, significant; P < 0.01, highly significant). Surface characteristics analyses revealed that XRD showed predominant tetragonal (t) zirconia crystal phase for all test groups. Mean surface roughness (Sa) of Group I was 41.83 nm, and it was significantly lesser than that of Group II (115.65 nm) and Group III (102.43 nm). Mean contact angles were 98.26°, 86.77°, and 68.03° for Groups I, II, and III, respectively, and these differences were highly significant. Mean pre-immersion Ca content in SBF was found to be 159 mg/L. Mean post-immersion Ca content was 70.10, 60.80, and 56.20 mg/L for Groups I, II, and III, respectively. Significant differences were found between Group I as compared to both Groups II and III. Bioactivity of Group III was marginally, but insignificantly higher with respect to Group II. Groups II and III were insignificant with respect to each other. Post-immersion XRD revealed predominant "t" phase, and SEM-EDX revealed well-formed, abundant calcium apatite layer on the treated samples as compared to that on untreated sample and an increasing Ca/P ratio from 1.15, 1.79 to 2.08, respectively from Group I to Group III. CONCLUSION: Within the limitations of this study, both sandblasting and UVP significantly and similarly improved bioactivity of zirconia as compared to the untreated samples, which was corroborated by the SEM-EDX results.

Comparative evaluation of wear resistance of CAD-CAM zirconia and cast cobalt chromium alloy for indirect restorations against human enamel - An In Vitro study.

PURPOSE OF THE STUDY: To comparatively evaluate the wear resistance of two different posterior indirect restorative materials against human enamel. MATERIALS AND METHODS: Two different posterior indirect restorative materials of ten in each Group-I (Monolithic zirconia) (n = 10) and Group-II (Cast cobalt chromium) (n = 10) were formed into disc and used as a substrate for the wear test. Freshly extracted mandibular first premolars were used as a pin (antagonist) (n = 20). Pin-on-disc wear testing machine was used to simulate the masticatory parameters and evaluation of the wear parameters was done after 1,20,000 cycles, with load of 40N for specific duration. Data related to wear testing procedure were tabulated and evaluated. Results were statistically analyzed using Mann-Whitney test and Wilcoxon signed rank test. RESULTS: Mean surface roughness value (Ra value) obtained for Group-I disc test samples showed no statistical significance (P value < 0.05). Mean wear rate value of test disc samples was statistically significant between Group-I and Group-II (P value < 0.05). Mean surface roughness value was statistically significant between Groups-I and II before and after wear test (P value < 0.05). CONCLUSION: From the results obtained, it was found that the Group-I (Monolithic zirconia) exhibited higher wear resistance than Group-II (cast cobalt chromium) and causes less wear to the opposing enamel antagonist.

Evaluation of the Bioactivity of Surface Modified Polyetheretherketone (PEEK) as an Implant Material: An In Vitro Study.

PURPOSE: The purpose of this study was to evaluate the bioactivity of polyetheretherketone (PEEK) used as an implant material after surface modification by electron beam deposition of titanium. MATERIALS AND METHODS: Twenty-two samples of PEEK were obtained from a single manufacturer, water jet sectioned, and divided randomly into two groups of eleven each (Group I and Group II). Eleven PEEK samples from Group II were coated with Grade II commercially pure titanium by electron beam deposition technique. One representative sample from each group was evaluated for surface roughness, topography and composition using three dimensional surface profilometer, scanning electron microscope coupled with energy dispersive X-ray (SEM-EDX) analysis. Simulated body fluid (SBF) was prepared and calcium (Ca) content in it was quantitatively analyzed by inductively coupled plasma mass spectrometry (ICP-MS) technique. Ten samples from each group were then immersed in SBF for a period of 21 days and amount of calcium depletion was analyzed to determine the bioactivity of two groups. Surface characteristics and elemental composition of immersed samples were analyzed by SEM-EDX and correlated with results of ICP-MS tests. The data obtained were then subjected to statistical analysis using independent t-test. RESULTS: Group II samples showed a significant increase in surface roughness compared to Group I (P < 0.02). There were significant differences in Ca depletion of Group I and Group II samples when compared to preimmersion Ca content (P < 0.001). When compared between two Groups, Group II samples showed higher Ca depletion (P < 0.001). CONCLUSION: Within the limitations of this study, it was concluded that PEEK dental implants which were surface modified by electron beam deposition of titanium had enhanced bioactivity when compared to unmodified PEEK. Hence, they can serve as a valuable alternative to conventional dental implant materials.

Comparative evaluation of the wear resistance of two different implant abutment materials after cyclic loading - An in vitro study.

PURPOSE: To comparatively evaluate the wear resistance of two different implant abutment materials with titanium implants after cyclic loading. METHODOLOGY: Two groups utilizing 20 titanium implants secured in resin blocks, in which 10 titanium implants are connected with titanium abutments (Group I, n = 10) and the other 10 titanium implants are connected with Polyether ether Ketone (PEEK) abutments (Group II, n = 10). Abutments are cyclically loaded for 550,000 cycles. Surface profilometry, scanning electron microscopy (SEM), and energy-dispersive X-ray spectrometry (EDS) are carried out for all the abutment in both Group I and Group II before and after cyclic loading. The abutment surface at the implant-abutment interface is analyzed for wear. RESULTS: On comparison using independent "t"-test, it was found that the mean difference values of pre- and post-cyclic loading surface roughness (Ra value) of Group I (premachined titanium straight abutments) (-0.073 µm) was lower than the Group II test samples (premachined PEEK straight abutments) (-0.0004 µm), and this was found to be statistically insignificant (P = 0.272). SEM micrographs and EDS results also corroborate with the results of surface profilometry. CONCLUSION: The new concept in this study is Group II (PEEK abutments) are connected with titanium implants, to prove its compatibility and aesthetics. Within the limitations of the study, the surface roughness values before and after cyclic loading of two different abutment materials revealed that the wear resistance of titanium abutments is more than PEEK abutments, but the difference was found to be statistically insignificant.

Comparative evaluation of the effect of electrolyzed oxidizing water on surface detail reproduction, dimensional stability and Surface texture of poly vinyl siloxane impressions.

AIM: The aim of this in vitro study was to comparatively evaluate the effect of chemical disinfectants on the surface detail reproduction, dimensional stability and surface texture of polyvinyl siloxane (PVS) impressions. MATERIALS AND METHODS: The impressions were then divided into five groups (fifteen samples per group) and subjected to a ten minutes immersion with 2% glutaraldehyde (Group I), 1% sodium hypochlorite (Group II), freshly prepared electrolyzed oxidizing water (EOW) with different pH values - acidic (Group III), alkali (Group IV) and neutral (Group V). The samples were examined pre and post-immersion under visual observation for surface detail reproduction, travelling microscope for measurement of dimensional stability and surface profilometer (3D) for evaluation of surface texture. A standardized master die was fabricated and seventy-five PVS test samples were made. The samples were subjected to immersion disinfection and studied for surface detail reproduction, dimensional stability and surface texture. Post-hoc test, paired t test and ANOVA were used to analyze dimensional stability statistically both within and between the test groups. RESULTS: The surface detail reproduction was satisfactory with both pre and post-immersion test samples. A statistically significant dimensional change was observed post-immersion in Groups II, III and V test samples and a statistically insignificant dimensional change was observed in Groups I and IV test samples. There was a negligible change in surface texture post-immersion in Groups I, III, IV and V test samples with a slight increase in surface roughness post-immersion in Group II samples. CONCLUSION: In this study, all the test disinfectants produced satisfactory surface detail reproduction on Polyvinyl siloxane impressions. 2% glutaraldehyde and electrolyzed oxidizing water (alkali) have resulted in statistically insignificant dimensional change, while 1% sodium hypochlorite, electrolyzed oxidizing water (acidic) and electrolyzed oxidizing water (neutral) have resulted in statistically significant dimensional changes. All the test disinfectants except 1% sodium hypochlorite showed a reduction in surface roughness (Ra) values.

Comparative Evaluation of the Masking Ability of Lithium Disilicate Ceramic with Different Core Thickness on the Shade Match of Indirect Restorations over Metallic Substrate: An In vitro Study.

PURPOSE: The purpose of this in vitro study was to comparatively evaluate the masking ability of lithium disilicate ceramic with different core thickness on the shade match of indirect restorations over metallic substrate. MATERIALS AND METHODS: A total of 30 heat pressed lithium disilicate ceramic discs of low translucency were fabricated with diameter 10mm and thickness of 1 mm, 1.3 mm and 1.6mm with each thickness consisting of 10 samples to be used in the study. Thirty Ni-Cr metal discs of diameter 10mm were used to simulate metallic substrates .The colour difference of the lithium disilicate ceramic disc before and after cementation were measured using CIE LAB system. RESULTS: The mean colour difference (ΔE) of Group I,Group II, Group III before cementation with the Ni-Cr metal discs was 17.32,13.01 and 11.73 respectively. The mean colour difference (ΔE) of Group I,Group II, Group III after cementation with the Ni-Cr metal discs was 16.32,12.10, 11.05 respectively. CONCLUSION: The mean colour difference of the three groups were found to be more than the clinically acceptable perceptibility threshold (ΔE < 3.3) indicative of reduced masking ability of all the three groups of ceramic discs over metallic substrate used in this study.

Three-dimensional finite element analysis of the stress distribution pattern in the design modifications of U-shaped palatal major connector.

BACKGROUND: The U-shaped maxillary major connector is considered to be the least-desirable design by many prosthodontists as it lacks rigidity, which is a primary requisite for a major connector. AIMS AND OBJECTIVES: Design modifications in the U-shaped palatal major connector are desired because it lacks rigidity. The study also aimed to determine the best design when a U-shaped palatal major connector is indicated for clinical use. MATERIALS AND METHODS: The normal design and the design-modified models (modification 1, 2, 3, 4) were loaded at the functional cusps of the premolars and the molars with a magnitude of 200 N, 250 N and 300 N at angulations of 60 o and 90 o on both sides of the maxillary arch. Results for each loading were obtained as stress distribution colored images and numerical values were recorded. A three-dimensional finite element analysis study of the design-modified models was performed using two finite element softwares, namely PRO-E and IDEAS. RESULTS: The least stress value of 7.86 Megapascals (MPa) at 200 N, 60 o was recorded for the double-thickness design, followed by design 1, which was 8.03 MPa. The least stress value for the palatal mucosa and ligament was provided by design modification 1 (0.5 mm-thick U-shaped connector, 9 mm anteroposteiorly, 14.6 mm laterally), which was 9.78 MPa and 2.98 MPa, respectively. CONCLUSION: The double-thickness group exhibited the least internal stress for the U-shaped major connector. However, it delivered the greatest stress to the palatal mucosa and the periodontal ligaments.