Effects of sorbitol and lactate on erythropoietin production in HepG2 cells.

Promotion of erythropoietin (EPO) production is important for erythropoiesis as well as cell viability. The most effective inducing factor for EPO production is hypoxia. Hypoxia inducible factor (HIF), a regulator of EPO production, is increased under hypoxic conditions and is also affected by various regulators such as sirtuin1 (SIRT1). SIRT1 is regulated by the cytoplasmic redox state, which is thought to affect EPO production. Therefore, we investigated the effects of sorbitol and lactic acid, which serve as substrates for cellular respiration and bring cells into a reduced state, on EPO production in HepG2 cells. The addition of low-concentration sorbitol to HepG2 cells produced a mildly reduced state similar to that of hypoxia and increased NAD+, SIRT1, and HIF-α, and EPO mRNA expression. On the other hand, lactate suppressed EPO mRNA expression at all concentrations. Inhibition of lactate production from pyruvate abolished the effect of low sorbitol concentrations on EPO mRNA expression. When low-concentration sorbitol and a reducing agent were administered simultaneously, the effect of increasing EPO mRNA expression disappeared. It was suggested that SIRT1 and EPO production increased under conditions where lactate production was not suppressed, even under mildly reduced conditions similar to hypoxia.

Group 1 ITI Consensus Report: The influence of implant length and design and medications on clinical and patient-reported outcomes.

OBJECTIVES: The aim of Working Group 1 was to address the influence of different local (implant length, diameter, and design) and systemic (medications) factors on clinical, radiographic, and patient-reported outcomes in implant dentistry. Focused questions on (a) short posterior dental implants (≤6 mm), (b) narrow diameter implants, (c) implant design (tapered compared to a non-tapered implant design), and (d) medication-related dental implant failures were addressed. MATERIALS AND METHODS: Four systematic reviews were prepared in advance of the Consensus Conference and were discussed among the participants of Group 1. Consensus statements, clinical recommendations, and recommendations for future research were based on structured group discussions until consensus was reached among the entire expert Group 1. The statements were then presented and accepted following further discussion and modifications as required by the plenary. RESULTS: Short implants (≤6 mm) revealed a survival rate ranging from 86.7% to 100%, whereas standard implant survival rate ranged from 95% to 100% with a follow-up from 1 to 5 years. Short implants demonstrated a higher variability and a higher Risk Ratio [RR: 1.24 (95% CI: 0.63, 2.44, p = 0.54)] for failure compared to standard implants. Narrow diameter implants (NDI) have been classified into three categories: Category 1: Implants with a diameter of <2.5 mm ("Mini-implants"); Category 2: Implants with a diameter of 2.5 mm to <3.3 mm; Category 3: Implants with a diameter of 3.3 mm to 3.5 mm. Mean survival rates were 94.7 ± 5%, 97.3 ± 5% and 97.7 ± 2.3% for category 1, 2 and 3. Tapered versus non-tapered implants demonstrated only insignificant differences regarding clinical, radiographic, and patient-reported outcomes. The intake of certain selective serotonin reuptake inhibitors and proton pump inhibitors is associated with a statistically significant increased implant failure rate. The intake of bisphosphonates related to the treatment of osteoporosis was not associated with an increased implant failure rate. CONCLUSIONS: It is concluded that short implants (≤6 mm) are a valid option in situations of reduced bone height to avoid possible morbidity associated with augmentation procedures; however, they reveal a higher variability and lower predictability in survival rates. Narrow diameter implants with diameters of 2.5 mm and more demonstrated no difference in implant survival rates compared to standard diameter implants. In contrast, it is concluded that narrow diameter implants with diameters of less than 2.5 mm exhibited lower survival rates compared to standard diameter implants. It is further concluded that there are no differences between tapered versus non-tapered dental implants. Certain medications such as selective serotonin reuptake inhibitors and proton pump inhibitors showed an association with a higher implant failure rate.

The effect of hemin-induced oxidative stress on erythropoietin production in HepG2 cells.

Erythropoietin (EPO) and iron are both indispensable hematopoietic factors and are often studied in humans and rodents. Iron activates prolyl hydroxylases (PHDs) and promotes the degradation of the α-subunit of hypoxia inducible factor (HIF), which regulates EPO production. Iron also causes oxidative stress. Oxidative stress leads to alterations in the levels of multiple factors that regulate HIF and EPO production. It is thought that iron influences EPO production by altering two pathways, namely PHDs activity and oxidative stress. We studied the differential effect of varying concentrations of hemin, an iron-containing porphyrin, on EPO production in HepG2 cells. Hemin at 100 µM reduced EPO mRNA expression. The hemin-induced reduction of EPO mRNA levels was attenuated at concentrations greater than 200 µM and EPO production increased in the presence of 500 µM hemin. In comparison, protoporphyrin IX, iron-free hemin did not influence EPO mRNA expression. Additionally, malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) activity significantly increased with 300 µM hemin. Importantly, the antioxidant tempol inhibited the hemin-induced (500 µM) increase in EPO mRNA levels. In conclusion, these results suggest that restraint of EPO production by hemin was offset by the promotion of EPO production by hemin-induced oxidative stress at hemin concentrations greater than 300 µM.

Simultaneous sinus lifting and alveolar distraction of a severely atrophic posterior maxilla for oral rehabilitation with dental implants.

We retrospectively reviewed a new preimplantation regenerative augmentation technique for a severely atrophic posterior maxilla using sinus lifting with simultaneous alveolar distraction, together with long-term oral rehabilitation with implants. We also analyzed the regenerated bone histomorphologically. This study included 25 maxillary sinus sites in 17 patients. The technique consisted of alveolar osteotomy combined with simultaneous sinus lifting. After sufficient sinus lifting, a track-type vertical alveolar distractor was placed. Following a latent period, patient self-distraction was started. After the required augmentation was achieved, the distractor was left in place to allow consolidation. The distractor was then removed, and osseointegrated implants (average of 3.2 implants per sinus site, 80 implants) were placed. Bone for histomorphometric analysis was sampled from six patients and compared with samples collected after sinus lifting alone as controls (n = 4). A sufficient alveolus was regenerated, and all patients achieved stable oral rehabilitation. The implant survival rate was 96.3% (77/80) after an average postloading followup of 47.5 months. Good bone regeneration was observed in a morphological study, with no significant difference in the rate of bone formation compared with control samples. This new regenerative technique could be a useful option for a severely atrophic maxilla requiring implant rehabilitation.