Remineralizing potential of the biomimetic P11-4 self-assembling peptide on noncavitated caries lesions: A retrospective cohort study evaluating semistandardized before-and-after radiographs.

BACKGROUND: Self-assembling peptide (SAP) P11-4 was introduced to treat initial caries lesions by means of guiding hydroxyapatite regeneration within the lesion. The objective of this study was to assess its effectiveness in a practical clinical setting. METHODS: Caries lesions in permanent teeth treated with monomeric and polymeric SAP P11-4 from May 2015 through October 2020 were retrospectively analyzed at lesion and child levels by means of bite-wing radiography for changes in stage and cavitation and restoration. RESULTS: Two hundred and nineteen children aged 10 through 19 years with a total of 405 proximal lesions in posterior teeth were followed from 0.4 through 5.5 years (median, 7 months; interquartile range, 6-19 months). Regression occurred in 37% of stage RA1 (radiolucency in the outer one-half of enamel) (95% CI, 31% to 44%), 38% of stage RA2 (radiolucency in the inner one-half of enamel plus or minus the enamel-dentin junction) (95% CI, 30% to 45%), and 40% of stage RA3 (radiolucency limited to the outer one-third of dentin) (95% CI, 16% to 68%) lesions. The proportion of lesions with no cavitation was 0.96 (95% CI, 0.94 to 0.98) after 1 year and 0.91 (95% CI, 0.88 to 0.95) after 2 years. CONCLUSIONS: Real-world clinical data indicate that SAP P11-4 can lead to recovery and a healthier tooth stage. PRACTICAL IMPLICATIONS: SAP P11-4 is a safe treatment for initial caries lesions in permanent teeth that remineralizes in the deepest zone of the lesion and can be introduced easily into routine dental practice.

[Refresher Orthogeriatrics]. / Orthogeriatrie.

Fragility fractures are associated with a substantial mortality and morbidity. Because of the high prevalence of comorbidities and a high risk of complications the application of geriatric principles in the complex treatment of these patients is vital. The last years have seen a paradigm shift in the treatment of fragility fractures from an orthopedic disorder towards an orthogeriatric syndrome. This article reviews the orthogeriatric principles of treating fragility fractures.

Infliction of proteotoxic stresses by impairment of the unfolded protein response or proteasomal inhibition as a therapeutic strategy for mast cell leukemia.

The intensity and duration of endoplasmic reticulum (ER) stress converts the unfolded protein response (UPR) from an adaptive into a terminal response. The first regulates homeostasis, the latter triggers apoptosis. Cells that rapidly proliferate and possess developed secretory capabilities, such as leukemia cells, depend on an efficiently operating UPR to maintain proteostasis. Activation of terminal UPR by either blockade of adaptive UPR or exaggeration of ER stress has been explored as a novel approach in cancer therapy. For mast cell leukemia (MCL) the efficacy of both approaches, by utilizing the KITV560G,D816V-positive MCL cell line HMC-1.2, was investigated. We show that HMC-1.2 cells display a tonic activation of the IRE1α arm of the UPR, which constitutively generates spliced XBP1. Inhibition of IRE1α by different types of inhibitors (MKC-8866, STF-083010, and KIRA6) suppressed proliferation at concentrations needed for blockade of IRE1α-mediated XBP1 splicing. At higher concentrations, these inhibitors triggered an apoptotic response. Blocking the proteasome by bortezomib, which confers an exaggerated UPR, resulted in a marked cytotoxic response. Bortezomib treatment also caused activation of the kinase JNK, which played a pro-proliferative and anti-apoptotic role. Hence, the combination of bortezomib with a JNK inhibitor synergized to induce cell death. In summary, the UPR can be addressed as an effective therapeutic target against KITD816V-positive MCL.

The combined effect of fludarabine monophosphate and radiation as well as gemcitabine and radiation on squamous carcinoma tumor cell lines in vitro.

PURPOSE: Despite proven antitumor activity of gemcitabine in chemoradiotherapy of advanced head and neck cancer, many authors refer to severe acute and late local and haematological toxicity. Fludarabine does imply nearly the same mechanisms of action as gemcitabine, inhibiting various enzymes involved in DNA replication. This investigation focuses on the combined effect of either fludarabine or gemcitabine and radiation on human squamous carcinoma cell lines in vitro, providing data for future decisions on head and neck chemoradiotherapy regimen. MATERIALS AND METHODS: ZMK-1, A549, BW-225, GR-145, OH-65 and CaSki cell lines were incubated with either drug at defined schedules and irradiated at a single fraction dose of 2 Gy every 24 hours up to 8 Gy. Cytotoxic effects were measured by colony-forming assays, quantitative determination of apoptosis and isobologram analysis. RESULTS: Incubation of fludarabine led to a radiosensitizing effect in the A549, CaSki and ZMK-1 cell lines and an additive effect in the BW-225, GR-145 and OH-65 cell lines. Treatment with gemcitabine only indicated significant radiosensitization in the CaSki cell line in combination with augmented resistance against gemcitabine application alone. CONCLUSIONS: Our results reveal a potential radiosensitizing effect of fludarabine and its possible application in chemoradiotherapy of advanced head and neck carcinoma and possibly other tumor entities.

Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease.

We have recently shown that the hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) is neuroprotective in rodent stroke models, and that this action appears to be mediated via a neuronal G-CSF receptor. Here, we report that the G-CSF receptor is expressed in rodent dopaminergic substantia nigra neurons, suggesting that G-CSF might be neuroprotective for dopaminergic neurons and a candidate molecule for the treatment of Parkinson's disease. Thus, we investigated protective effects of G-CSF in 1-methyl-4-phenylpyridinium (MPP+)-challenged PC12 cells and primary neuronal midbrain cultures, as well as in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Substantial protection was found against MPP+-induced dopaminergic cell death in vitro. Moreover, subcutaneous application of G-CSF at a dose of 40 microg/Kg body weight daily over 13 days rescued dopaminergic substantia nigra neurons from MPTP-induced death in aged mice, as shown by quantification of tyrosine hydroxylase-positive substantia nigra cells. Using HPLC, a corresponding reduction in striatal dopamine depletion after MPTP application was observed in G-CSF-treated mice. Thus our data suggest that G-CSF is a novel therapeutic opportunity for the treatment of Parkinson's disease, because it is well-tolerated and already approved for the treatment of neutropenic conditions in humans.