Parathyroid hormone PTH(1–34) increases the volume, mineral content, and mechanical properties of regenerated mineralizing tissue after distraction osteogenesis in rabbits

Background and purpose Parathyroid hormone (PTH) has attracted considerable interest as a bone anabolic agent. Recently, it has been suggested that PTH can also enhance bone repair after fracture and distraction osteogenesis. We analyzed bone density and strength of the newly regenerated mineralized tissue after intermittent treatment with PTH in rabbits, which undergo Haversian bone remodeling similar to that in humans

Heterologous mesenchymal stem cells successfully treat femoral pseudarthrosis in rats

<p>Abstract</p> <p>Background</p> <p>This study evaluated the effectiveness of treating pseudarthrosis in rats by using bone marrow cell suspensions or cultures of bone marrow mesenchymal stromal cells</p> <p>Methods</p> <p>Thirty-eight specific pathogen-free (SPF) animals were randomly assigned to four groups: Group 1, Control, without surgical intervention; Group 2 (Placebo), experimental model of femoral pseudarthrosis treated only with saline solution; Group 3, experimental model of femoral pseudarthrosis treated with heterologous bone marrow cells suspension; Group 4, experimental model of femoral pseudarthrosis treated with cultures of heterologous mesenchymal stromal cells from bone marrow. When pseudarthrosis was confirmed by simple radiological studies, digital radiography and histopathology after a 120-day postoperative period, Groups 2, 3 and 4 were treated as above. At 30, 60 and 90 days after the treatment, all animals were evaluated by simple radiological studies, and at the end of the experiment, the animals were assessed by computed axial tomography and anatomopathological and histomorphometric examinations.</p> <p>Results</p> <p>Injected cells were detected in the areas affected by pseudarthrosis using scintigraphy within the first 24 hours after their administration. After 60 days, the animals of Group 3 showed callus formation while the animals of Group 4 presented periosteal reaction and had some consolidated areas. In contrast, Group 2 showed a predominance of fibro-osteoid tissue. After 90 days, bone consolidation and remodeling was observed in all animals from Group 3 whereas animals from Group 4 exhibited partial consolidation and those ones from Group 2 persisted with pseudarthrosis.</p> <p>Conclusion</p> <p>The treatment with heterologous bone marrow cells suspension proved to be effective in the treatment of pseudarthrosis whereas cultures of heterologous bone marrow mesenchymal stromal cells did not show the same potential to aid bone healing.</p

DCs Pulsed with Novel HLA-A2-Restricted CTL Epitopes against Hepatitis C Virus Induced a Broadly Reactive Anti-HCV-Specific T Lymphocyte Response

OBJECTIVE: To determine the capacity of dendritic cells (DCs) loaded with single or multiple-peptide mixtures of novel hepatitis C virus (HCV) epitopes to stimulate HCV-specific cytotoxic T lymphocyte (CTL) effector functions. METHODS: A bioinformatics approach was used to predict HLA-A2-restricted HCV-specific CTL epitopes, and the predicted peptides identified from this screen were synthesized. Subsequent IFN-γ ELISPOT analysis detected the stimulating function of these peptides in peripheral blood mononuclear cells (PBMCs) from both chronic and self-limited HCV infected subjects (subjects exhibiting spontaneous HCV clearance). Mature DCs, derived in vitro from CD14(+) monocytes harvested from the study subjects by incubation with appropriate cytokine cocktails, were loaded with novel peptide or epitope peptide mixtures and co-cultured with autologous T lymphocytes. Granzyme B (GrB) and IFN-γ ELISPOT analysis was used to test for epitope-specific CTL responses. T-cell-derived cytokines contained in the co-cultured supernatant were detected by flow cytometry. RESULTS: We identified 7 novel HLA-A2-restricted HCV-specific CTL epitopes that increased the frequency of IFN-γ-producing T cells compared to other epitopes, as assayed by measuring spot forming cells (SFCs). Two epitopes had the strongest stimulating capability in the self-limited subjects, one found in the E2 and one in the NS2 region of HCV; five epitopes had a strong stimulating capacity in both chronic and self-limited HCV infection, but were stronger in the self-limited subjects. They were distributed in E2, NS2, NS3, NS4, and NS5 regions of HCV, respectively. We also found that mDCs loaded with novel peptide mixtures could significantly increase GrB and IFN-γ SFCs as compared to single peptides, especially in chronic HCV infection subjects. Additionally, we found that DCs pulsed with multiple epitope peptide mixtures induced a Th1-biased immune response. CONCLUSIONS: Seven novel and strongly stimulating HLA-A2-restricted HCV-specific CTL epitopes were identified. Furthermore, DCs loaded with multiple-epitope peptide mixtures induced epitope-specific CTLs responses

Relationship Between Osteonecrosis of the Jaw and Bisphosphonate Treatment

Terapija bisfosfonatima i njezina etiopatogenetska povezanost s aseptičkom osteonekrozom čeljusti važan je javnozdravstveni problem današnjice. Svrha je rada pregledom suvremene znanstvene literature utvrditi posljedice višestrukog djelovanja bisfosfonata (antiosteoklastična aktivnost, citotoksičnost na meka i koštana tkiva, antiangiogeneza, genski čimbenici, poremećena ravnoteža između osteoklasta i osteoblasta). Terapija bisfosfonatima jedan je od najčešćih uzroka razvoja osteonekroze čeljusti. Epidemiološki podaci pokazuju da se javlja u bolesnika koji su uzimali jedan ili kombinanciju nitrogenih bisfosfonata. Najvažniji čimbenici rizika za ovu nuspojavu su vrsta bisfosfonata (napose visokopotentni pamidronat i zoledronat koji se daju intravenski), njihova doza i duljina medikacije te vrsta bolesti zbog koje se propisuje terapija. Pojava osteonekroze čeljusti zabilježena je uglavnom u onkoloških bolesnika i u samo 5 % bolesnika s osteoporozom koji su liječeni bisfosfonatima. U patogenezi osteonekroze povezane s bisfosfonatima važno je, sa stajališta dentalnomedicinske prakse, dobro opće oralno zdravlje jer se osteonekroza javlja napose nakon prethodnoga parodontološkog i oralnokirurškog zahvata.Bisphosphonate treatment and its aetiopathogenic association with aseptic osteonecrosis of the jaw is one of the more prominent public health issues today. The aim of this review is to see into the mechanisms of bisphosphonate effects on bones described in literature (anti-osteoclastic activity, cytotoxicity, antiangiogenesis, genetic factors, and imbalance between osteoclasts and osteoblasts). Bisphosphonate treatment is the dominant cause of jaw necrosis. Epidemiological data show an exclusive incidence of osteonecrosis of the jaw in patients who took one or a combination of nitrogen-containing bisphosphonates. Risk factors vary by the bisphosphonate potency (particularly risky are the highly potent pamidronate and zoledronate, which are given intravenously), dosage, duration of treatment, and the illness. Jaw necrosis is most common in oncology patients, and only 5 % in patients with osteoporosis. From a dental-medical point of view, a good oral health is important because osteonecrosis often appears after a periodontal or oral surgical procedure