Prosthodontic and Surgical Management of a Completely Edentulous Patient with a Severe Class III Skeletal Maxillomandibular Relationship: A Clinical Report

This article describes a multidisciplinary approach combining surgical and prosthodontic treatment of a completely edentulous patient who presented with a severe skeletal class III relationship and was diagnosed as American College of Prosthodontists Prosthodontic Diagnostic Index (ACP PDI) class IV. The use of a complete denture serving as diagnostic tool, surgical guide, and definitive restoration is presented. Computer‐aided surgical simulation was used to achieve an accurate diagnostic and surgical plan. Maxillary Lefort class I and mandibular sagittal split osteotomy surgical treatment was performed to correct arch discrepancy. The surgical procedure demonstrated a clinically acceptable maxillomandibular relationship and stability. The patient was satisfied with the esthetics and demonstrated improved oral function following prosthesis insertion.     

Treatment of a Patient with Severely Worn Dentition: A Clinical Report

This clinical report documents the prosthodontic treatment of a Prosthodontic Diagnostic Index Class IV 63-year-old white male, referred to the prosthodontic clinic by his general dentist for evaluation and treatment. The patient was concerned about the severe wear on his teeth and understood the need for comprehensive (full-mouth) rehabilitation to restore his dental condition. The clinical findings, diagnosis, treatment plan, and sequence of treatment are presented.     

Adenanthin targets proteins involved in the regulation of disulphide bonds

Adenanthin has been recently shown to inhibit the enzymatic activities of peroxiredoxins (Prdx) I and II through its functional α,β-unsaturated ketone group serving as a Michael acceptor. A similar group is found in SK053, a compound recently developed by our group to target the thioredoxin–thioredoxin reductase (Trx–TrxR) system. This work provides evidence that next to Prdx I and II adenanthin targets additional proteins including thioredoxin–thioredoxin reductase system as well as protein disulfide isomerase (PDI) that contain a characteristic structural motif, referred to as a thioredoxin fold. Adenanthin inhibits the activity of Trx-TR system and PDI in vitro in the insulin reduction assay and decreases the activity of Trx in cultured cells. Moreover, we identified Trx-1 as an adenanthin binding protein in cells incubated with biotinylated adenanthin as an affinity probe. The results of our studies indicate that adenanthin is a mechanism-selective, rather than an enzyme-specific inhibitor of enzymes containing readily accessible, nucleophilic cysteines. This observation might be of importance in considering potential therapeutic applications of adenanthin to include a range of diseases, where aberrant activity of Prdx, Trx–TrxR and PDI is involved in their pathogenesis.     

Immunization with Leishmania donovani protein disulfide isomerase DNA construct induces Th1 and Th17 dependent immune response and protection against experimental visceral leishmaniasis in Balb/c mice

In the present study, the efficacy of Leishmania donovani protein disulfide isomerase (LdPDI) as a DNA vaccine was evaluated in BALB/C mice. Mice immunized with the LdPDI-DNA construct were found to be the most immuno-reactive, as the construct induced higher T-cell proliferation. The increased T-cell proliferation was associated with a substantial rise in Th1 and Th17+ CD4 cell response and triggered a higher proportion of CD8+ T cells for the release of interferon-gamma along with a reduced splenic parasite load on Days20 and 60 post challenge (PC). Furthermore, the vaccine construct triggered increased interferon (IFN)-γ, interleukin(IL)-17A, and IL-22 release accompanied by decreased extracellular signal-regulated kinases (ERK) 1/2 signaling and increased mitogen-activated protein kinase (MAPK) signaling coinciding with an increase in the amount of nitrite and reactive oxygen species (ROS)in vaccinating the splenocyts. We summarize from our data that the PDI-DNA construct of Leishmania donovani has the potential to elicit protective immunity through the pro-inflammatory cytokines of CD8+ and CD4+(Th1 and Th17) following an intervention in the downstream signaling event of ERK1/2 (probably through p38MAPK signaling). Therefore, the study suggests a new control against visceral leishmaniasis in the future.     

Neonatal Brain Injury and Timing of Neurodevelopmental Assessment in Patients With Congenital Heart Disease

Background

Brain injury (BI) is reported in 60% of newborns with critical congenital heart disease as white matter injury (WMI) or stroke. Neurodevelopmental (ND) impairments are reported in these patients. The relationship between neonatal BI and ND outcome has not been established.

Disulfide bond exchanges in integrins αIIbβ3 and αvβ3 are required for activation and post-ligation signaling during clot retraction

Background

Integrin αIIbβ3 mediates platelet adhesion, aggregation and fibrin clot retraction. These processes require activation of αIIbβ3 and post-ligation signaling. Disulfide bond exchanges are involved in αIIbβ3 and αvβ3 activation.

Methods

In order to investigate the role of integrin activation and disulfide bond exchange during αIIbβ3- and αvβ3-mediated clot retraction, we co-expressed in baby hamster kidney cells wild-type (WT) human αIIb and WT or mutated human β3 that contain single or double cysteine substitutions disrupting C523-C544 or C560-C583 bonds. Flow cytometry was used to measure surface expression and activation state of the integrins. Time-course of fibrin clot retraction was examined.

Results

Cells expressed WT or mutated human αIIbβ3 as well as chimeric hamster/human αvβ3. The αIIbβ3 mutants were constitutively active and the thiol blocker dithiobisnitrobenzoic acid (DTNB) did not affect their activation state. WT cells retracted the clot and addition of αvβ3 inhibitors decreased the retraction rate. The active mutants and WT cells activated by anti-LIBS6 antibody retracted the clot faster than untreated WT cells, particularly in the presence of αvβ3 inhibitor. DTNB substantially inhibited clot retraction by WT or double C523S/C544S mutant expressing cells, but minimally affected single C523S, C544S or C560S mutants. Anti-LIBS6-enhanced clot retraction was significantly inhibited by DTNB when added prior to anti-LIBS6.

Conclusions

Both αIIbβ3 and αvβ3 contribute to clot retraction without prior activation of the integrins. Activation of αIIbβ3, but not of αvβ3 enhances clot retraction. Both αIIbβ3 activation and post-ligation signaling during clot retraction require disulfide bond exchange.     

阿尔茨海默病模型大鼠PDI及P53的表达及丁苯酞对其的影响

目的 研究阿尔茨海默病模型大鼠PDI、P53的表达及丁苯酞对其影响.方法 成年雄性SD大鼠60只,随机分为模型组、丁苯酞组及对照组,每组20只;通过向大鼠海马内注射Aβ1-42建立阿尔茨海默病模型,喂养60d后用Y型迷宫检测大鼠学习记忆能力、免疫组织化学染色检测大鼠脑组织PDI和P53的表达.结果 与对照组比较,模型组大鼠学习记忆能力下降,其海马CA1区PDI阳性细胞减少,皮层P53表达增加,差异均有统计学意义(P＜0.01);与模型组比较,丁苯酞组大鼠海马CA1区PDI阳性细胞数明显增加,皮层P53表达减少,差异有统计学意义(P＜0.01).结论 丁苯酞改善阿尔茨海默病大鼠学习记忆能力可能与其增加PDI、抑制P53的表达有关.     

Orthodontics Using an Occlusal Splint: A Clinical Report

Careful management of the occlusion is necessary for successful prosthodontic treatment. A reorganized occlusal approach requires a more accurate registration of the desired jaw position, and where it is difficult to achieve this, an occlusal splint is indicated. This clinical report documents a 60‐year‐old man with a Prosthodontic Diagnostic Index Class IV dentition, who prior to a full‐mouth reconstruction, underwent occlusal splint therapy with a Michigan‐type splint that incorporated z‐springs to allow concurrent orthodontic tooth movement of two anterior teeth to positions that would allow favorable restorations by correcting occlusal and esthetic form.