Influence of titanium surfaces on attachment of osteoblast-like cells in vitro

Implant surface topography influences osteoblastic proliferation, differentiation and extracellular matrix protein expressions. Studies on preliminary interactions of osteoblast-like cells on implant interface through in vitro systems, can give lucid insights to osseo-integrative efficacies of when in vivo implants. In the present investigation two titanium surfaces of dental implants, a sandblasted and acid-etched surface and an experimental grooved surface were compared through in vitro systems. The titanium implants were seeded with osteoblast-like primary cells and maintained for a period of 1-7 days. Expressions of fibronectin and osteonectin were assessed through immunogold labelling by scanning electron microscopy. The grooved surface, supported better osteoblastic cell adhesion and proliferation than the rough surfaces. Further, osteoblastic cells on the grooved surfaces also displayed a strong labelling for fibronectin at the cytoplasmic extensions coupled with intense osteonectin expression in comparison to the rough surfaced implants. In conclusion, grooved surfaces offered better cell attachment and proliferation than the other rough surfaces studied.     

Outcomes of Older Patients in the Recent Era of Heart Kidney Transplantation

Background and ObjectiveVariable age thresholds are often used at transplant centers for simultaneous heart and kidney transplantation (HKT). We hypothesize that selected older recipients enjoy comparable outcome to younger recipients in the current era of HKT.MethodsWe performed a retrospective analysis of HKT outcomes in the United Network for Organ Sharing (UNOS) registry from 2006 to 2018, classifying patients by age at transplant as ≥ 65 or < 65 years. The primary outcome was patient death. Secondary outcomes included all-cause kidney graft failure and death-censored kidney allograft failure.ResultsOf 973 patients, 774 (80%) were younger than 65 years (mean 52 ± 10 years) and 199 (20%) were 65 years or older (mean 67 ± 2 years). The older HKT cohort had fewer blacks (22% vs 35%, P = .01) and women (12 vs 18%, P = .04). Fewer older patients received dialysis (30% vs 54%, P < .001) and mechanical support (36% vs 45%, P = .03) before HKT. Older recipients received organs from slightly older donors. The median follow-up time was shorter for patients 65 years or older than for the younger group (2.3 vs 3.3 years, P < .001). Patient survival was similar between the groups (mean 8.8 vs 9.8 years, P = .3), with the most common causes of death being cardiovascular (29%) and infectious complications (28%). There was no difference in all-cause kidney graft survival (mean 8.7 vs 9.3 years, P = .8). Most commonly, recipients died with a functional renal allograft (59.8%), and this occurred more commonly in older patients (81.4% vs 54.8%, P = .001). Cox proportional hazard modeling showed that higher donor age (hazard ratio [HR] 1.015, P = .01; HR 1.022, P = .02) and use of pre-transplant dialysis (HR 1.5, P = .004; HR 1.8, P = .006) increased the risk for both all-cause and death-censored kidney allograft failure, respectively.ConclusionsOur study showed that carefully selected older patients have outcomes similar to those of a younger cohort and argues for comprehensive evaluation of the recipients with age as part of comorbidity assessment rather than use of an arbitrary age threshold for candidacy.     

Structure and activity of the axon guidance protein MICAL

During development, neurons are guided to their targets by short- and long-range attractive and repulsive cues. MICAL, a large multidomain protein, is required for the combined action of semaphorins and plexins in axon guidance. Here, we present the structure of the N-terminal region of MICAL (MICAL(fd)) determined by x-ray diffraction to 2.0 A resolution. The structure shows that MICAL(fd) is an FAD-containing module structurally similar to aromatic hydroxylases and amine oxidases. In addition, we present biochemical data that show that MICAL(fd) is a flavoenzyme that in the presence of NADPH reduces molecular oxygen to H(2)O(2) (K(m,NAPDH) = 222 microM; k(cat) = 77 sec(-1)), a molecule with known signaling properties. We propose that the H(2)O(2) produced by this reaction may be one of the signaling molecules involved in axon guidance by MICAL.     

Interleukin-12-induced cytotoxicity against syngeneic B cell lymphomas of SJL/J mice

The B cell lymphomas (RCS) that develop spontaneously in 90% of aging SJL/J mice stimulate syngeneic CD4+ Vbeta16+ Th2 cells to produce cytokines, such as IL-4 and IL-5, which promote lymphoma growth. Although RCS cells express a unique superantigen (vSAg) encoded by an endogenous MMTV (Mtv-29) provirus that also elicits IFN-gamma production from na?ve syngeneic lymphoid cells, there is no development of RCS-specific cytotoxicity. However, addition of IL-12 to co-cultures of SJL spleen and irradiated (gamma-)RCS cells resulted in the appearance of effector cells that killed RCS and NK-susceptible target cells. Antibody depletion studies revealed at least two types of RCS/IL-12-induced cytotoxic cells: (1) NK cells (Asialo GM1+) and (2) CD8+ CTL. Despite high titers of IFN-gamma in the SN of co-culture of SJL spleen and gamma-RCS cells, cytotoxicity only developed if IL-12 was also included in the co-cultures. The results of RNAse protection assays and multi-parameter FACS analysis demonstrated an upregulation of IFN-gamma and decrease in IL-4 by activated Th cells in co-cultures with IL-12. These results indicate that inclusion of IL-12 in primary co-cultures of SJL spleen and gamma-RCS cells influences the qualitative nature of the response to favor use of RCS-responsive Th1 rather than Th2 cells to facilitate the production of cytotoxic effector cells. Results of in vivo experiments support this hypothesis, as judged by tumor growth assays and FACS analysis of the tumor cell content of lymphoid tissues. Inhibition of lymphoma growth was observed in mice given gamma-RCS/IL-12-induced effector cells prior to injection of viable RCS cells. These results demonstrate that IL-12 can be used to alter the host immune response leading to induction of cytotoxic effector cells that inhibit the development and/or progressive growth of otherwise resistant B cell lymphomas in SJL/J mice.     

Temporomandibular Joint Osteoarthritis: Diagnosis and Long-Term Conservative Management: A Topic Review

Degenerative joint disease (DJD), a common osteoarthritic problem encountered in clinical practice presents as a chronic debilitating disease resulting in altered joint structure due to degradation and loss of articular cartilage, along with changes in the subchondral bone and other soft tissues. DJD is a frequent finding in the Temporomandibular joints (TMJs). Consequently, a good understanding of the use of a diagnostic algorithm will lead to a better control of DJD in the TMJ. The etiopathogenesis of osteoarthritis is complex, and it is associated with multiple risk factors. The condition progresses slowly through different phases with periods of remission and activity finally reaching the burnout phase. Conservative management forms the cornerstone for the treatment of most of these cases. This review attempts to acquaint the dentist with the diagnosis, pathogenesis and general characteristics of the disease while highlighting and updating them with the current conservative treatment algorithms in order to assist in the formulation of a treatment plan for these patients.     

Preparation of 177Lu‐labeled Nimotuzumab for radioimmunotherapy of EGFR‐positive cancers: Comparison of DOTA and CHX‐A″‐DTPA as bifunctional chelators

This study was aimed at evaluating the role of bifunctional chelators DOTA‐NCS and CHX‐A″‐DTPA‐NCS used for conjugating ¹⁷⁷Lu with Nimotuzumab on the radiochemical yields, purity, in vitro stability, and specificity of the radioimmunoconjugates to EGFR. Two immunoconjugates were prepared wherein Nimotuzumab was conjugated with the acyclic ligand p‐NCS‐Bn‐CHX‐A″‐DTPA and macrocyclic ligand p‐NCS‐Bn‐DOTA. These were radiolabeled with ¹⁷⁷Lu, purified on PD‐10 column, and characterized by SE‐HPLC. In vitro stability was determined up to 4 days post preparation. Specificity of the radioimmunoconjugates was ascertained by in vitro studies in A431 cells while the biodistribution patterns were studied in normal Swiss mice up to 96 hours post injection. Four to five molecules of CHX‐A″‐DTPA/DOTA were attached to one molecule of Nimotuzumab. Radiochemical purity of both ¹⁷⁷Lu‐CHX‐A″‐DTPA‐Nimotuzumab and ¹⁷⁷Lu‐DOTA‐Nimotuzumab was determined to be greater than 98%. Both the radioimmunoconjugates exhibited good in vitro stability at 37°C up to 4 days post preparation in saline, and their clearance was largely by the hepatobiliary route. The DOTA‐ and CHX‐A″‐DTPA‐based radioimmunoconjugates could be prepared with good radiochemical purity, in vitro stability, and specificity to EGFR. Further studies in EGFR‐positive cancers would pave way for them for use in the clinics.     

A phase II trial of bevacizumab and everolimus as treatment for patients with refractory,progressive intracranial meningioma

Meningiomas that progress after standard therapies are challenging with limited effective chemotherapy options. This phase II trial evaluated the efficacy of everolimus plus bevacizumab in patients with recurrent, progressive meningioma after treatment with surgical resection and local radiotherapy when appropriate. Patients with recurrent meningioma (WHO grade I, II, or III) following standard treatments with surgical resection and radiotherapy received bevacizumab (10 mg/kg IV days 1 and 15) and everolimus (10 mg PO daily) each 28 day cycle. Evaluation of response occurred every 2 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, overall survival and safety. Seventeen patients with a median age of 59 years (29–84) received study treatment. WHO grades at study entry included: I, 5 (29?%); II, 7 (41?%); III, 4 (24?%); unknown, 1 (6?%). Patients received a median of 8 cycles (1–37); all patients are off study treatment. A best response of SD was observed in 15 patients (88?%), and 6 patients had SD for >12 months. Overall median PFS was 22 months (95?% CI 4.5–26.8) and was greater for patients with WHO grade II and III compared to grade I tumors (22.0 months vs 17.5 months). Four patients discontinued treatment due to toxicity (proteinuria, 2; colitis, 1, thrombocytopenia, 1). However, other grade 3 toxicity was uncommon, and no patient had grade 4 toxicity. The combination of everolimus and bevacizumab was well-tolerated, and produced stable disease in 88?% of patients; the median duration of disease stabilization of 10 months (2–29). The median PFS from this prospective trial was similar to previous retrospective reports of bevacizumab in the treatment of recurrent meningioma.     

Quality Matters–Hematopoietic Stem Cell Transplantation <Emphasis Type="Italic">versus</Emphasis> Transfusion and Chelation in Thalassemia Major

Objective

To compare quality of life of children with thalassemia major who have undergone stem cell transplantation with those on regular transfusion.

Methods

The study included 40 children who underwent transplantation and 40 children and 20 adults on regular transfusion and iron chelation therapy. The quality of life assessment was done using the Pediatric Quality of Life Inventory 4.0 Generic Core Scale.

Results

The mean total summary score, psychosocial summary score and physical score was 92, 91 and 92.8, respectively in transplant group and 83, 82.7 and 83.6, respectively in children in transfusion group. The adult group on transfusion showed overall poorer scores of 74.9, 76 and 73.9, respectively. The average scores in all domains were significantly (P<0.05) lower and drop steeply in second decade in transfusion group.

Conclusion

Allogeneic stem cell transplantation improves quality of life in thalassemia major.

     

Interface reaction at dental implants inserted in condensed bone

Purpose: The influence of the osteotome technique on the interface reaction of cylinder implants (SLA, ITI^®) was compared with the interface reaction of conventional implant insertion in an animal model. Material and methods: A total of 64 implants were placed in the cranial and caudal tibia of 8 Göttinger minipigs. The implant site was prepared either by a conventional technique with drills (control group A) or by the osteotome technique (experimental group B). Bone tissue responses were evaluated by histomorphometry, fluorescence microscopy and scanning electron microscopy after 7 and 28 days of osseointegration. Results: The average initial (7 days) bone‐to‐implant contact ratio was not statistically significantly different for the osteotome technique (35.88±2.94%) than for the control group (43.78±3.39%, P<0.095). After 28 days, the bone‐to‐implant contact ratio became statistically significantly higher when implants were inserted by conventional preparation (44.81±3.07% (group B), 63.47±4.87% (group A), P=0.003). Whereas fluorescence and immunhistologic examination revealed new bone formation with osteocalcin deposition directly at the implant surface in both groups, the extent of direct bone/implant contact was enhanced in conventionally prepared implant sites. SEM analysis confirmed an intimate bone to implant bond without fibrous tissue formation in places of direct contact at an ultrastructured level. Conclusion: Implant placement in conventionally prepared implantation sites is accompanied by an improved interface formation at an early stage of implantation.