Maximal dose-response of vitamin-K2 (menaquinone-4) on undercarboxylated osteocalcin in women with osteoporosis

2020 ◽  
Vol 90 (1-2) ◽  
pp. 42-48 ◽  
Author(s):  
Tusar K Giri ◽  
David Newton ◽  
Opal Chaudhary ◽  
Elena Deych ◽  
Nicola Napoli ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Dose Response ◽  
Geometric Mean ◽  
Serum Vitamin ◽  
Osteoporotic Fractures ◽  
Vitamin K2 ◽  
Vertebral Compression Fractures ◽  
High Dose ◽  
Undercarboxylated Osteocalcin ◽  
High Concentrations

Abstract. Low concentrations of serum vitamin K accompany high concentrations of undercarboxylated osteocalcin (ucOC) and osteoporotic fractures. Although vitamin K2 (MK-4) is approved as a therapeutic agent for the treatment of osteoporosis in some countries, the dose-response is unknown. The objective of this study was to assess the improvement in carboxylation of osteocalcin (OC) in response to escalating doses of MK-4 supplementation. A nine-week, open-labeled, prospective cohort study was conducted in 29 postmenopausal women who suffered hip or vertebral compression fractures. Participants took low-dose MK-4 (0.5 mg) for 3 weeks (until the second visit), then medium-dose MK-4 (5 mg) for 3 weeks (until the third visit), then high-dose MK-4 (45 mg) for 3 weeks. The mean ±  SD age of the participants was 69 ± 9 years. MK-4 dose (p < 0.0001), but neither age nor other relevant medications (e.g. bisphosphonates) correlated with improvement in %ucOC. As compared to baseline concentrations (geometric mean ±  SD) of 16.8 ± 2.4, 0.5 mg supplementation halved %ucOC to 8.7 ± 2.2 (p < 0.0001) and the 5-mg dose halved %ucOC again (to 3.9 ± 2.2; p = 0.0002 compared to 0.5-mg dose). However, compared to 5 mg/day, there was no additional benefit of 45 mg/day (%ucOC 4.6; p = NS vs. 5-mg dose). MK-4 supplementation resulted in borderline increases in γ-carboxylated osteocalcin (glaOC; p = 0.07). There were no major side effects of MK-4 supplementation. In postmenopausal women with osteoporotic fractures, supplementation with either 5 or 45 mg/day of MK-4 reduces ucOC to concentrations typical of healthy, pre-menopausal women.

Potential for Single High-Dose Influenza Immunization in Unprimed Children

PEDIATRICS ◽  
1982 ◽  
Vol 70 (6) ◽  
pp. 982-986 ◽  
Author(s):  
Peter A. Gross ◽  
Gerald V. Quinnan ◽  
Pureza F. Gaerlan ◽  
Carolyn R. Denning ◽  
Anne Davis ◽  
...  
Keyword(s):  
New York ◽  
Influenza A ◽  
Standard Dose ◽  
Geometric Mean ◽  
High Dose ◽  
York Metropolitan Area ◽  
Reaction Index ◽  
Number Of Patients ◽  
Sibling Control ◽  
High Concentrations

High concentrations of split-product vaccine (SPV) are more immunogenic than lower concentrations. These studies were verified with another influenza strain, B/Singapore/22/79. Two ether-treated SPVs were compared in 80 children and young adults. The vaccine strains were influenza A/Bangkok/79, A/Brazil/78, and B/Singapore /79; 44 patients received a high-dose SPV containing 7, 7, and 60 µg each of the respective hemagglutinins (HA) and 36 received a standard dose SPV containing 7, 7, and 7 µg of HA, respectively. Among persons initially seronegative by hemagglutination inhibition (HAI) tests, the geometric mean titer (GMT) in 15 recipients of one high dose was 97 vs GMT of 37 in 18 recipients of one standard dose (P &lt; .05). Furthermore, 87% of high-dose recipients had HAI titer ≥ 40 vs 44% of standard dose recipients. In initially seropositive persons, GMT in 29 recipients of one high dose was 170 vs GMT of 84 in 18 recipients of one standard dose (P &lt; .05). Immune response to the other two virus strains was comparable for the two vaccines. The reaction index for the high dose vaccine was 0.70 vs 0.45 for the standard dose (P = NS). An A/Bangkok epidemic struck the New York metropolitan area. The attack rate in unvaccinated matched sibling control subjects was 35% (15/43). There were no vaccine failures. In conclusion, in the small number of patients studied, a 60-µg HA dose of B/Singapore/79 was significantly more immunogenic than a standard 7-µg HA dose without an increase in reactogenicity.

MO578OSTEOCALCIN AND VASCULAR CALCIFICATION IN HEMODIALYSIS PATIENTS: AN OBSERVATIONAL COHORT STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hesham Kamal Habeeb Keryakos ◽  
Ahmed Salama ◽  
Nagwa Okaily ◽  
Mariam Boulis
Keyword(s):  
Vascular Calcification ◽  
Strong Predictor ◽  
Serum Vitamin ◽  
Hemodialysis Patients ◽  
Vitamin K2 ◽  
Maintenance Hemodialysis ◽  
Undercarboxylated Osteocalcin ◽  
Median Serum ◽  
K Deficiency ◽  
Observational Cohort

Abstract Background and Aims Vascular calcification contributes to morbidity and mortality in patients with ESRD on maintenance hemodialysis. to study the relationship between osteocalcin and vascular calcification. Method 160 patients with ESRD on maintenance hemodialysis and 60 age-and sex-matched healthy controls were recruited. Serum vitamin K2 and osteocalcin both intact and undercarboxylated were measured. Transthoracic echocardiography was done for valvular calcification and thickening, and carotid duplex was done for carotid intimal medial calcification and thickening. Results Hemodialysis patients have higher median serum vitamin K2 (p&lt;0.001), higher undercarboxylated osteocalcin (p&lt;0.001). Only older age, duration of hypertension, and duration of established cardiovascular disease are associated with carotid media-intimal calcification. Old age is a strong predictor of carotid media intimal thickening. Female sex is associated with valvular thickening. Conclusion Functional vitamin K deficiency is present in maintenance hemodialysis patients and serum osteocalcin is not associated with cardiovascular calcification.

scholarly journals Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women

2016 ◽  
Vol 175 (6) ◽  
pp. 541-549 ◽  
Author(s):  
Sofie Hertz Rønn ◽  
Torben Harsløf ◽  
Steen Bønløkke Pedersen ◽  
Bente Lomholt Langdahl
Keyword(s):  
Placebo Group ◽  
Trabecular Bone ◽  
Postmenopausal Women ◽  
Bone Structure ◽  
Bone Microarchitecture ◽  
Vitamin K2 ◽  
Undercarboxylated Osteocalcin ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Age Related

Objective Clinical studies suggest that vitamin K2 protects against bone loss and fractures; however, its effect on bone quality has never been investigated. We investigated the effect of vitamin MK-7 on undercarboxylated osteocalcin (ucOC), and bone mass and quality. Design We conducted a randomised, placebo-controlled, double-blinded clinical trial. Methods We investigated the effect of MK-7 375 µg for 12 months on bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA), bone microarchitecture measured by high-resolution peripheral quantitative computed tomography (HRpQCT) and biochemical bone turnover markers in 148 postmenopausal women with osteopenia. All of them were supplemented with calcium and vitamin D. Results ucOC decreased in the MK-7 group (−65.6 (59.1; 71.0) %) (median (CI)) compared with the placebo group (−6.4 (−13.5; 1.2) %) after 3 months (P < 0.01). HRpQCT after 12 months demonstrated that trabecular number in tibia was unchanged in the MK-7-group (−0.1 ± 1.9%) (mean ± s.d.) and decreased in the placebo group (−3.5 ± 2.2%), trabecular spacing was unchanged in the MK-7 group (+1.2 ± 8.0%) and increased in the placebo group (+4.5 ± 9.7%), and trabecular thickness was unchanged in the MK-7 group (+0.2 ± 1.7%) and increased in the placebo group (+4.0 ± 2.2%) (between-group changes for all: P < 0.05). There were no significant differences between the groups in HRpQCT-derived parameters at the radius or in BMD at any site. Conclusion The changes in bone microarchitecture in the placebo group are consistent with the age-related deterioration of trabecular structure, with a loss of trabeculae and a greater mean thickness of the remaining trabeculae. This suggests that vitamin MK-7 preserves trabecular bone structure at the tibia.

Does coffee, tea and caffeine consumption reduce the risk of incident breast cancer? A systematic review and network meta-analysis

2021 ◽  
pp. 1-13
Author(s):  
Shu Wang ◽  
Xiang Li ◽  
Yue Yang ◽  
Jingping Xie ◽  
Mingyue Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Postmenopausal Women ◽  
Meta Analysis ◽  
High Dose ◽  
Dependent Manner ◽  
Tea Consumption ◽  
Case Control Studies ◽  
High Concentration ◽  
Coffee Intake

Abstract Objective: We aimed to evaluate the association between coffee and/or tea consumption and breast cancer (BC) risk among premenopausal and postmenopausal women and to conduct a network meta-analysis. Design: Systematic review and network meta-analysis. Setting: We conducted a systematic review of electronic publications in the last 30 years to identify case–control studies or prospective cohort studies that evaluated the effects of coffee and tea intake. Results: Forty-five studies that included more than 3 323 288 participants were eligible for analysis. Network meta-analysis was performed to determine the effects of coffee and/or tea consumption on reducing BC risk in a dose-dependent manner and differences in coffee/tea type, menopause status, hormone receptor and the BMI in subgroup and meta-regression analyses. According to the first pairwise meta-analysis, low-dose coffee intake and high-dose tea intake may exhibit efficacy in preventing ER(estrogen receptor)− BC, particularly in postmenopausal women. Then, we performed another pairwise and network meta-analysis and determined that the recommended daily doses were 2–3 cups/d of coffee or ≥5 cups/d of tea, which contained a high concentration of caffeine, particularly in postmenopausal women. Conclusions: Coffee and tea consumption is not associated with a reduction in the overall BC risk in postmenopausal women and is associated with a potentially lower risk of ER− BC. And the highest recommended dose is 2–3 cups of coffee/d or ≥5 cups of tea/d. They are potentially useful dietary protectants for preventing BC.

High dose ascorbic acid treatment in COVID-19 patients raised some problems in clinical chemistry testing

2020 ◽  
Vol 45 (5) ◽  
pp. 491-498
Author(s):  
Fatih Yesildal ◽  
Ferruh Kemal Isman
Keyword(s):  
Ascorbic Acid ◽  
Ldl Cholesterol ◽  
Clinical Chemistry ◽  
Assay Method ◽  
High Dose ◽  
Serum Samples ◽  
Choice Of Treatment ◽  
High Concentrations ◽  
Clinical Chemistry Tests ◽  
Abbott Architect

AbstractObjectiveCOVID-19 pandemia still continues to threaten the whole world. High dose ascorbic acid (AA) infusion is a choice of treatment and its efficiency is still being investigated. AA interferes with many clinical chemistry tests. However, data about the interference of high concentrations of AA is not sufficient. In this study, we aimed to investigate the interference of AA at high concentrations on commonly used chemistry assays.Materials and MethodsSerum samples at AA concentrations of 200, 150, 100, 75, 50, 25, 10, 5, 2 and 0 mg/dL were prepared by using the stock solution of 15000 mg/dL AA. Each sample was analyzed by using the most common 30 chemistry tests (Abbott Architect C8000, Illinois, USA) and a POCT glucometer (STANDARD GlucoNavii, Gyeonggi-do, Republic of Korea).ResultsCreatinine, sodium and glucose (POCT) tests were found to be positively interfered by increasing AA concentrations; while direct bilirubin, lipase, UIBC, triglyceride, total cholesterol, HDL/LDL cholesterol tests were negatively interfered. Absolute interference (%) increased as the AA concentration increased.ConclusionThis is the largest and first study to investigate the interference of high dose AA, which is used in severe COVID-19 patients nowadays. Manufacturers and clinicians should be aware of the possibility of aberrant results due to high dose AA infusion. Clinicians should not forget to consult a laboratory specialist, since he is the only person to monitor the reactions in all assays, and know the technical subjects like interferences, assay method specifications. This issue is very important for correct decision-making and interpretation of the data-mining studies accurately and efficiently.

scholarly journals High-dose oral and intravenous rifampicin for the treatment of tuberculous meningitis in predominantly HIV-positive Ugandan adults: a phase II open-label randomised controlled trial

2021 ◽  
Author(s):  
Fiona V Cresswell ◽  
David B Meya ◽  
Enock Kagimu ◽  
Daniel Grint ◽  
Lindsey te Brake ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Tuberculous Meningitis ◽  
Geometric Mean ◽  
Standard Of Care ◽  
Hiv Positive ◽  
High Dose ◽  
Open Label ◽  
Dose Oral ◽  
Csf Levels

Abstract Background High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in HIV co-infection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. Methods In this phase II open-label trial, Ugandan adults with suspected TBM were randomised to standard-of-care control (PO-10, rifampicin 10mg/kg/day), intravenous rifampicin (IV-20, 20mg/kg/day), or high-dose oral rifampicin (PO-35, 35mg/kg/day). We performed PK sampling on day 2 and 14. The primary outcomes were total exposure (AUC0-24), maximum concentration (Cmax), CSF concentration and grade 3-5 adverse events. Results We enrolled 61 adults, 92% were HIV-positive, median CD4 count was 50cells/µL (IQR 46–56). On day 2, geometric mean plasma AUC0-24hr was 42.9h.mg/L with standard-of-care 10mg/kg dosing, 249h.mg/L for IV-20 and 327h.mg/L for PO-35 (P&lt;0.001). In CSF, standard-of-care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC0-24hr 0.27mg/L, compared with 1.74mg/L (95%CI 1.2–2.5) for IV-20 and 2.17mg/L (1.6–2.9) for PO-35 regimens (p&lt;0.001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (p=0.34) Conclusion Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe, and respectively resulted in exposures ~6- and ~8-fold higher than standard-of-care, and CSF levels above the MIC

Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in mulitple sclerosis and autoimmune disorders

1998 ◽  
Vol 4 (2) ◽  
pp. 63-69 ◽  
Author(s):  
O A Khan ◽  
H Jiang ◽  
P S Subramaniam ◽  
H M Johnson ◽  
S S Dhib-Jalbut
Keyword(s):  
Therapeutic Option ◽  
High Dose ◽  
Interferon Tau ◽  
Unique Type ◽  
Immune Mediated ◽  
High Concentrations ◽  
Ifn Treatment ◽  
High Doses ◽  
Mulitple Sclerosis

The interferons (IFN) are a family of complex proteins possessing antiviral, antiproliferative, and immunomodulatory activities. Two type 1 recombinant human IFN have been recently approved for the treatment of multiple sclerosis (MS). However, use of high dose type 1 IFN treatment in MS patients has been limited by dose-related toxicity. Ovine IFNt is a unique type 1 interferon discovered for its role in the animal reproductive cycle. It differs from other type 1 IFNs in that it is remarkably less toxic even at high concentrations, is able to cross species barriers, and is not inducible by viral infection. Ovine IFNt has been shown to be very effective in the treatment of animal models of MS. In this study, we examined the toxicity of OvIFNt on human T-cells at high doses and its immunregulatory properties at equivalent doses. Our experiments confirmed the remarkably non-toxic nature of OvIFNt on human cells at high concentrations as well as immunomodulating properties consistent with other type 1 IFNs including an antilymphoproliferative effect and inhibition of IFNg-induced HLA class II expression. These results suggest that OvIFNt could be developed into a potentially less toxic therapeutic option for immune-mediated disorders including MS.

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