Effect of calcium phosphate compound (MZF-CaP) with and without fluoride in preventing bone loss in ovariectomized rats

Zinc (Zn) has been shown to inhibit osteoclast differentiation, promote osteoblast activity, and enhance the bone formation. Zinc-containing calcium phosphate (Zn-TCP) implanted in rabbit femoral defect was demonstrated to stimulate bone formation. Other studies demonstrated that calcium phosphate compounds (MZF-CaP) incorporating magnesium (Mg2+), zinc and fluoride (F-) when administered either by injection or orally were effective in preventing bone loss (osteoporosis) induced by estrogen deficiency (ovariectomy) in a rat model. The objective of the present study was to investigate the preventive effect of similar compound, with F (MZF-CaP-L, MZF-CaP-H) and without F (MZ-CaP-L), when injected in ovariectomized (OVX) rats. MZF-CaP-L and MZ-CaP-L were prepared by precipitation at 90oC and MZF-CaP-H was prepared by sintering MZF-CaP-L at 900oC. The release of the ions from acidic buffer was determined. Suspensions of Zn-TCP, MZF-CaP-H, MZF-CaP-L and MZ-CaP-L (617 μg in 0.2 ml of 1% sodium alginate saline solution) were injected intramuscularly under anesthesia into 5-week-old OVX rats on Zn-deficient diet. One week after surgery, bone mineral density (BMD) and bone mineral content (BMC) of the rat femurs were measured using X-ray CT. The injections and X-ray CT and Zn ion plasma measurements were repeated every week for 12 weeks. The rats were sacrificed and the femurs removed after 12 weeks. Bone mechanical strength was evaluated using the three-point bending test. MZ-CaP-L (without F), compared to the other compounds, showed the highest increase in the Zn2+ ion plasma concentration, and the highest BMD, BMC and mechanical strength

Characteristics of Persistent Symptoms Manifested after SARS-CoV-2 Vaccination: An Observational Retrospective Study in a Specialized Clinic for Vaccination-Related Adverse Events

Background: Although many adverse reactions after SARS-CoV-2 vaccination have been reported, there have been few comprehensive studies on persistent symptoms after SARS-CoV-2 vaccination. The aim of this study was to determine the clinical characteristics of patients with various persistent symptoms after SARS-CoV-2 vaccination. Methods: A retrospective descriptive study was performed for patients who visited a specialized clinic established at Okayama University Hospital to evaluate adverse events after SARS-CoV-2 vaccination during the period from April 2021 to March 2023. Results: Descriptive analysis was performed for 121 of 127 patients who visited the clinic during the study period, and separate analysis was performed for the other 6 patients who had serious complications, who required treatment with prednisolone, and who had persistent symptoms. The median [interquartile range] age of the patients was 48 years [31-64 years], and the patients included 44 males (36.4%) and 77 females (63.6%). The most frequent symptoms were sensory impairment (34 patients, 28.1%), general fatigue (30 patients, 24.8%), fever/low-grade fever (21 patients, 17.4%), and headache (21 patients, 17.4%). Serious complications included myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), sarcoidosis, aseptic meningitis, neuromyelitis optica spectrum disorders (NMOSDs), tendon adhesions, and idiopathic thrombocytopenia. Conclusions: Although causal relationships were not determined, 15 persistent symptoms after SARS-CoV-2 vaccination were characterized. All of the symptoms had onset from 12 hours to one week after vaccination, with 10 symptoms persisting for 6 months or longer. The most frequent symptom was sensory impairment

Gender-Dependent Characteristics of Serum 1,25-Dihydroxyvitamin D/25-Hydroxyvitamin D Ratio for the Assessment of Bone Metabolism

Y Objectives Vitamin D deficiency, which is common worldwide, increases the risks of falls and fractures and can lead to increased morbidity and mortality. However, the clinical utility and relevance of vitamin D activation remain unknown. The aim of the present study was to clarify the clinical usefulness of serum 1,25-dihydroxyvitamin D (1,25D)/25-hydroxyvitamin D (25D) ratio for assessment of the extent of bone metabolism. Methods We retrospectively screened data for 87 patients whose serum 1,25D and 25D levels were measured. Eight patients who were taking vitamin D preparations were excluded, and data for 79 patients (33 males and 46 females) were analyzed. Since menopausal status can be associated with serum vitamin D level, we divided the patients by gender and divided the female patients into two groups at the age of 50 years. Results The median serum 1,25D/25D ratio was significantly lower in males than in females, with the most considerable difference in all males [4.1 (interquartile range: 2.3-5.8) x 10(-3)] versus elderly females (aged >= 50 years) [7.9 (3.3-10.1) x 10(-3)). Main disorders were endocrine (30.6%), inflammatory (18.5%), and bone related (16.7%) disorders. The ratios of serum 1,25D/25D had significant negative correlations with femoral dual-energy X-ray absorptiometry % young adult mean (DEXA %YAM) (R=-0.35) and lumbar DEXA %YAM (R=-0.32). Significant correlations were found between the 1,25D/25D ratio and serum levels of inorganic phosphate (iP), parathyroid hormone, and alkaline phosphatase (ALP). The 1,25D/25D ratio had gender specific characteristics: the ratio was significantly correlated with age in males (R=-0.49), while it was significantly correlated with BMI in females (R=0.34). Conclusions The results of this study suggested that vitamin D activity is negatively correlated with bone mineral density, being reduced in aged males but enhanced in obese females

Effect of calcium phosphate compound (MZF-CaP) with and without fluoride in preventing bone loss in ovariectomized rats

Zinc (Zn) has been shown to inhibit osteoclast differentiation, promote osteoblast activity, and enhance the bone formation. Zinc-containing calcium phosphate (Zn-TCP) implanted in rabbit femoral defect was demonstrated to stimulate bone formation. Other studies demonstrated that calcium phosphate compounds (MZF-CaP) incorporating magnesium (Mg2+), zinc and fluoride (F-) when administered either by injection or orally were effective in preventing bone loss (osteoporosis) induced by estrogen deficiency (ovariectomy) in a rat model. The objective of the present study was to investigate the preventive effect of similar compound, with F (MZF-CaP-L, MZF-CaP-H) and without F (MZ-CaP-L), when injected in ovariectomized (OVX) rats. MZF-CaP-L and MZ-CaP-L were prepared by precipitation at 90oC and MZF-CaP-H was prepared by sintering MZF-CaP-L at 900oC. The release of the ions from acidic buffer was determined. Suspensions of Zn-TCP, MZF-CaP-H, MZF-CaP-L and MZ-CaP-L (617 μg in 0.2 ml of 1% sodium alginate saline solution) were injected intramuscularly under anesthesia into 5-week-old OVX rats on Zn-deficient diet. One week after surgery, bone mineral density (BMD) and bone mineral content (BMC) of the rat femurs were measured using X-ray CT. The injections and X-ray CT and Zn ion plasma measurements were repeated every week for 12 weeks. The rats were sacrificed and the femurs removed after 12 weeks. Bone mechanical strength was evaluated using the three-point bending test. MZ-CaP-L (without F), compared to the other compounds, showed the highest increase in the Zn2+ ion plasma concentration, and the highest BMD, BMC and mechanical strength

Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent

The skin is a protective interface between the internal organs and environment and functions not only as a physical barrier but also as an immune organ. However, the immune system in the skin is not fully understood. A member of the thermo-sensitive transient receptor potential (TRP) channel family, TRPM4, which acts as a regulatory receptor in immune cells, was recently reported to be expressed in human skin and keratinocytes. However, the function of TRPM4 in immune responses in keratinocytes has not been investigated. In this study, we found that treatment with BTP2, a known TRPM4 agonist, reduced cytokine production induced by tumor necrosis factor (TNF) α in normal human epidermal keratinocytes and in immortalized human epidermal keratinocytes (HaCaT cells). This cytokine-reducing effect was not observed in TRPM4-deficient HaCaT cells, indicating that TRPM4 contributed to the control of cytokine production in keratinocytes. Furthermore, we identified aluminum potassium sulfate, as a new TRPM4 activating agent. Aluminum potassium sulfate reduced Ca2+ influx by store-operated Ca2+ entry in human TRPM4-expressing HEK293T cells. We further confirmed that aluminum potassium sulfate evoked TRPM4-mediated currents, showing direct evidence for TRPM4 activation. Moreover, treatment with aluminum potassium sulfate reduced cytokine expression induced by TNFα in HaCaT cells. Taken together, our data suggested that TRPM4 may serve as a new target for the treatment of skin inflammatory reactions by suppressing the cytokine production in keratinocytes, and aluminum potassium sulfate is a useful ingredient to prevent undesirable skin inflammation through TRPM4 activation

Salvage surgery improves the treatment outcome of patients with residual/recurrent maxillary sinus cancer after superselective intra-arterial cisplatin infusion with concomitant radiation therapy

Purpose We have performed superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) for patients with maxillary sinus cancer. The promising treatment outcomes of this non-surgical treatment were reported in past studies. However, few clinical studies have been conducted to evaluate the outcome of salvage surgery following RADPLAT. The purpose of this study was to analyze the treatment outcomes of salvage surgery for patients with recurrent maxillary sinus cancer after RADPLAT. Methods We assessed 45 patients who had recurrence following RADPLAT between 1999 and 2017, and conducted a retrospective analysis. We excluded patients who did not complete RADPLAT. Patients were not considered to have completed RADPLAT if they underwent intra-arterial cisplatin less than three times or received a total radiation dose of less than 60 Gy. The primary endpoint was overall survival. The median follow-up period for surviving patients after recurrence was 5.1 years. Results Twenty-five of the 45 (56%) patients underwent salvage surgery. The 5-year overall survival rate was 68% in patients who underwent salvage surgery, while all patients who did not undergo salvage surgery died during the observation period. Fifteen of 24 (63%) patients with local recurrence underwent salvage surgery. Eight patients did not undergo salvage surgery because of unresectable disease; five of the eight patients had unresectable posterior extension. All nine patients with nodal recurrence underwent neck dissection. Conclusion Treatment outcomes of salvage surgery following RADPLAT were favorable enough for it to be generally recommended. To reduce unresectable recurrence, the posterior section should be eradicated by RADPLAT