Phylloquinone improves endothelial function, inhibits cellular senescence, and vascular inflammation.

Phylloquinon (PK) and menaquinones (MK) are both naturally occurring compounds belonging to vitamin K group. Present study aimed to comprehensively analyze the influence of PK in several models of vascular dysfunction to determine whether PK has vasoprotective properties, similar to those previously described for MK. Effects of PK and MK on endothelial dysfunction were studied in ApoE/LDLR-/- mice in vivo, in the isolated aorta incubated with TNF, and in vascular cells as regard inflammation and cell senescence (including replicative and stress-induced models of senescence). Moreover, the vascular conversion of exogenous vitamins to endogenous MK-4 was analyzed. PK, as well as MK, given for 8 weeks in diet (10 mg/kg) resulted in comparable improvement in endothelial function in the ApoE/LDLR-/- mice. Similarly, PK and MK prevented TNF-induced impairment of endothelium-dependent vasorelaxation in the isolated aorta. In in vitro studies in endothelial and vascular smooth muscle cells, we identified that both PK and MK displayed anti-senescence effects via decreasing DNA damage while in endothelial cells anti-inflammatory activity was ascribed to the modulation of NFκB activation. The activity of PK and MK was comparable in terms of their effect on senescence and inflammation. Presence of endogenous synthesis of MK-4 from PK in aorta and endothelial and smooth muscle cells suggests a possible involvement of MK in vascular effects of PK. In conclusion, PK and MK display comparable vasoprotective effects, which may be ascribed, at least in part, to the inhibition of cell senescence and inflammation. The vasoprotective effect of PK in the vessel wall can be related to the direct effects of PK, as well as to the action of MK formed from PK in the vascular wall.

Vitamin D and vitamin K1 as novel inhibitors of biofilm in Gram-negative bacteria.

BACKGROUND: The persistent surge in antimicrobial resistance represents a global disaster. The initial attachment and maturation of microbial biofilms are intimately related to antimicrobial resistance, which in turn exacerbates the challenge of eradicating bacterial infections. Consequently, there is a pressing need for novel therapies to be employed either independently or as adjuvants to diminish bacterial virulence and pathogenicity. In this context, we propose a novel approach focusing on vitamin D and vitamin K1 as potential antibiofilm agents that target Gram-negative bacteria which are hazardous to human health. RESULTS: Out of 130 Gram-negative bacterial isolates, 117 were confirmed to be A. baumannii (21 isolates, 17.9%), K. pneumoniae (40 isolates, 34.2%) and P. aeruginosa (56 isolates, 47.9%). The majority of the isolates were obtained from blood and wound specimens (27.4% each). Most of the isolates exhibited high resistance rates to ß-lactams (60.7-100%), ciprofloxacin (62.5-100%), amikacin (53.6-76.2%) and gentamicin (65-71.4%). Approximately 93.2% of the isolates were biofilm producers, with 6.8% categorized as weak, 42.7% as moderate, and 50.4% as strong biofilm producers. The minimum inhibitory concentrations (MICs) of vitamin D and vitamin K1 were 625-1250 µg mL-1 and 2500-5000 µg mL-1, respectively, against A. baumannii (A5, A20 and A21), K. pneumoniae (K25, K27 and K28), and P. aeruginosa (P8, P16, P24 and P27) clinical isolates and standard strains A. baumannii (ATCC 19606 and ATCC 17978), K. pneumoniae (ATCC 51503) and P. aeruginosa PAO1 and PAO14. Both vitamins significantly decreased bacterial attachment and significantly eradicated mature biofilms developed by the selected standard and clinical Gram-negative isolates. The anti-biofilm effects of both supplements were confirmed by a notable decrease in the relative expression of the biofilm-encoding genes cusD, bssS and pelA in A. baumannii A5, K. pneumoniae K28 and P. aeruginosa P16, respectively. CONCLUSION: This study highlights the anti-biofilm activity of vitamins D and K1 against the tested Gram-negative strains, which emphasizes the potential of these vitamins for use as adjuvant therapies to increase the efficacy of treatment for infections caused by multidrug-resistant (MDR) strains and biofilm-forming phenotypes. However, further validation through in vivo studies is needed to confirm these promising results.

Vitamin K content of Australian-grown horticultural commodities.

Vitamin K is a multi-function vitamin that has emerging roles in bone, brain and vascular health. Vitamin K composition data remain limited globally and Australia has lacked nationally representative data for vitamin K1 (phylloquinone) in horticultural commodities. Primary samples (n = 927) of 90 Australian-grown fruit, vegetable and nut commodities were purchased in three Australian cities. We measured vitamin K1/phylloquinone in duplicate in 95 composite samples using liquid chromatography with electrospray ionisation-tandem mass spectrometry. The greatest mean concentrations of vitamin K1/phylloquinone were found in kale (565 µg/100 g), baby spinach (255 µg/100 g) and Brussels sprouts (195 µg/100 g). The data contribute to the global collection of vitamin K food composition data. They add to the evidence that vitamin K1/phylloquinone concentrations vary markedly between geographic regions, supporting development of region-specific datasets for national food composition databases that do not yet contain data for vitamin K. Such data are needed globally.

Effects of radical scavengers for reactive oxygen species on vitamin K-induced phototoxicity under UVA irradiation.

Vitamin K possesses efficacy as a topical dermatological agent. However, vitamin K is phototoxic and susceptible to photodegradation. Herein, we investigated the mechanisms underlying the phototoxicity of phylloquinone (PK, vitamin K1) and menaquinone-4 (MK-4, vitamin K2) under ultraviolet A (UVA) irradiation using various reactive oxygen species (ROS) scavengers. This resulted in the production of superoxide anion radicals via type I and singlet oxygen via type II photodynamic reactions, which were quenched by the ROS scavengers: superoxide dismutase and sodium azide (NaN3). In HaCaT cells, MK-4 and PK induced the production of intracellular ROS, particularly hydrogen peroxide, in response to UVA irradiation. Furthermore, the addition of catalase successfully decreased maximum ROS levels by approximately 30%. NaN3 and catalase decreased the maximum reduction in cell viability induced by UVA-irradiated PK and MK-4 in cell viability by approximately 2-7-fold. Additionally, ROS scavengers had no effect on the photodegradation of PK or MK-4 at 373 nm. Therefore, the phototoxicities of PK and MK-4 were attributed to the generation of singlet oxygen and hydrogen peroxide, underscoring the importance of photoshielding in circumventing phototoxicity.

Vitamin K Status Based on K1, MK-4, MK-7, and Undercarboxylated Prothrombin Levels in Adolescent and Adult Patients with Cystic Fibrosis: A Cross-Sectional Study.

The available evidence on vitamin K status in cystic fibrosis (CF) is scarce, lacking data on vitamin K2 (menaquinones-MK). Therefore, we assessed vitamin K1, MK-4 and MK-7 concentrations (LC-MS/MS) in 63 pancreatic insufficient and modulator naïve CF patients, and compared to 61 healthy subjects (HS). Vitamin K1 levels did not differ between studied groups. MK-4 concentrations were higher (median <1st-3rd quartile>: 0.778 <0.589-1.086> vs. 0.349 <0.256-0.469>, p < 0.0001) and MK-7 levels lower (0.150 <0.094-0.259> vs. 0.231 <0.191-0.315>, p = 0.0007) in CF patients than in HS. MK-7 concentrations were higher in CF patients receiving K1 and MK-7 supplementation than in those receiving vitamin K1 alone or no supplementation. Moreover, vitamin K1 concentrations depended on the supplementation regime. Based on multivariate logistic regression analysis, we have found that MK-7 supplementation dose has been the only predictive factor for MK-7 levels. In conclusion, vitamin K1 levels in CF are low if not currently supplemented. MK-4 concentrations in CF patients supplemented with large doses of vitamin K1 are higher than in HS. MK-7 levels in CF subjects not receiving MK-7 supplementation, with no regard to vitamin K1 supplementation, are low. There do not seem to be any good clinical predictive factors for vitamin K status.

Post-bariatric pregnancy is associated with vitamin K1 deficiency, a case control study.

BACKGROUND: Maternal obesity is associated with adverse outcome for pregnancy and childbirths. While bariatric surgery may improve fertility and reduce the risk of certain pregnancy-related complications such as hypertension and gestational diabetes mellitus, there is a lack of evidence on the optimal nutritional monitoring and supplementation strategies in pregnancy following bariatric surgery. We aimed to assess the impact of bariatric surgery on micronutrients in post-bariatric pregnancy and possible differences between gastric bypass surgery and sleeve gastrectomy. METHODS: In this prospective case control study, we recruited 204 pregnant women (bariatric surgery n = 59 [gastric bypass surgery n = 26, sleeve gastrectomy n = 31, missing n = 2] and controls n = 145) from Akershus university hospital in Norway. Women with previous bariatric surgery were consecutively invited to study participation at referral to the clinic for morbid obesity and the controls were recruited from the routine ultrasound screening in gestational week 17-20. A clinical questionnaire was completed and blood samples were drawn at mean gestational week 20.4 (SD 4.5). RESULTS: The women with bariatric surgery had a higher pre-pregnant BMI than controls (30.8 [SD 6.0] vs. 25.2 [5.4] kg/m2, p < 0.001). There were no differences between groups regarding maternal weight gain (bariatric surgery 13.3 kg (9.6) vs. control 14.8 kg (6.5), p = 0.228) or development of gestational diabetes (n = 3 [5%] vs. n = 7 [5%], p = 1.000). Mean levels of vitamin K1 was lower after bariatric surgery compared with controls (0.29 [0.35] vs. 0.61 [0.65] ng/mL, p < 0.001). Multiadjusted regression analyses revealed an inverse relationship between bariatric surgery and vitamin K1 (B -0.26 ng/mL [95% CI -0.51, -0.04], p = 0.047) with a fivefold increased risk of vitamin K1 deficiency in post-bariatric pregnancies compared with controls (OR 5.69 [1.05, 30.77] p = 0.044). Compared with sleeve gastrectomy, having a previous gastric bypass surgery was associated with higher risk of vitamin K1 deficiency (OR 17.1 [1.31, 223.3], p = 0.030). CONCLUSION: Post-bariatric pregnancy is negatively associated with vitamin K1 with a higher risk of vitamin K1 deficiency in pregnancies after gastric bypass surgery compared with after sleeve gastrectomy. Vitamin K1 deficiency in post-bariatric pregnancy have potential risk of hypocoaguble state in mother and child and should be explored in future studies.

Short-term treatment with cholestyramine increases long-acting anticoagulant rodenticide clearance from rabbits without affecting plasma vitamin K1 levels or blood coagulation.

Administration of high-dose vitamin K1 (VK1) overcomes coagulopathy and bleeding elicited by acute poisoning with long-acting anticoagulant rodenticides (LAARs). However, long-term (months) treatment is required due to long LAAR biological half-lives that may lead to poor compliance and recurrent coagulopathy. The half-lives of LAARs are extended by slow metabolism, and similar to warfarin, are thought to undergo enterohepatic recirculation. We now show that treatment with the bile acid sequestrant cholestyramine (CSA) administered concomitantly with VK1 decreases plasma LAAR levels and increases LAAR fecal excretion. Daily CSA treatment for 14 days did not reduce plasma VK1 levels, or increase prothrombin time. Collectively, these data show that CSA accelerates LAAR clearance from rabbits without adverse effects on VK1 anticoagulation, and could provide an additional therapeutic option for treatment of LAAR poisoning.

[Anticoagulant rodenticide poisoning in dogs: Retrospective analysis of clinical and laboratory diagnostic data]. / Vergiftung mit Cumarinderivaten beim Hund: Retrospektive Analyse klinischer und labordiagnostischer Daten.

OBJECTIVE: In this retrospective study, patient records of dogs suffering from poisoning with coumarin derivatives were evaluated to characterize the clinical appearance more precisely. MATERIAL UND METHODS: Retrospective data analysis included 52 dogs with hemostaseologically proven anticoagulant rodenticide poisoning which were treated as inpatients at the Clinic for Small Animals between September 2011 and October 2018. RESULTS: In only 2 dogs (4%) the intake of poison could be observed with certainty. The most common clinical signs observed were reduced general behavior (79%), pallor of the mucosa (79%), anorexia (60%), and dyspnea/tachypnea (60%). In contrast, macroscopically visible internal and external bleedings occurred less frequently. Initially, all cases showed a highly altered prothrombin time and most patients a considerably prolonged activated partial thromboplastin time. Anemia was present in 75% of patients. All dogs included in the study received initially an intravenous treatment with 10 mg/kg vitamin K1. Pretreatment with 1 mg/kg prednisolone was given for prophylaxis of possible incompatibility reactions. No patient showed signs of anaphylactic reaction. Transfusions of whole blood or concentrated red cells were given to only 10 of the 52 animals; only one received 2 transfusions of erythrocytes. 94% of the animals could be discharged home for outpatient therapy after a median length of hospitalization of 3 days (1-9 days) with physiological or almost physiological coagulation test results. CONCLUSION: Anticoagulant rodenticide poisoning is often associated with non-specific symptoms and good prognosis if treated adequately. CLINICAL RELEVANCE: Coagulation diagnostics is always indicated in cases with unclear disorders. In life-threatening emergencies, immediate intravenous infusion of high-dose vitamin K1 is a very effective treatment and results in a rapid increase in coagulation factor activity.

Vitamin K (Menadione)-incorporated chitosan/alginate hydrogel as a novel product for periorbital hyperpigmentation.

The possibility of controlling periorbital hyperpigmentation disorders is one of the most important research goals in cosmetic preparations. In the current investigation, 1% vitamin K (Vit K) was incorporated into a Chitosan/alginate hydrogel which aimed to increase the dermal delivery and anti-pigmentation effect. The Vit K-hydrogel was evaluated using several different tests, including volume expansion/contraction analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), ultraviolet (UV) absorbance spectroscopy, and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Vit K hydrogel's drug release profile showed a steady increase over time. Furthermore, the modified Vit K hydrogel formulations showed no harmful effects in an in vitro cytotoxicity study. The Vit K hydrogel was tested for dermal irritation on Wistar rats, and the hydrogel was found to be non-irritating. Furthermore, Vit K-hydrogel inhibited melanin formation (31.76 ± 1.14%) and was remarkably higher than free Vit K. In addition, Vit K-hydrogel inhibited L-dopa auto-oxidation to a greater extent (94.80 ± 2.41%) in comparison with Vit K solution (73.95 ± 1.62%). Vit K-hydrogel enhanced percutaneous transport of Vit K, according to in vitro percutaneous absorption findings, suggesting that this innovative formulation may provide new therapeutic options for periorbital hyperpigmentation.

Vitamin K1 intake is associated with lower risk for all-cause and cardiovascular disease mortality in community-dwelling older Australian women.

BACKGROUND AND AIMS: Assessing the relationship between vitamin K1 intakes, using region-specific food databases, with both all-cause, and cardiovascular disease (CVD) mortality warrants further investigation to inform future preventative strategies. Consequently, we examined the aforementioned associations in the Perth Longitudinal Study of Ageing Women (PLSAW). METHODS AND RESULTS: 1436 community-dwelling older Australian women (mean ± SD age 75.2 ± 2.7 years) completed a validated food frequency questionnaire at baseline (1998). Vitamin K1 intake was calculated based on an Australian vitamin K food database, supplemented with published data. All-cause and CVD mortality data was obtained from linked health records. Associations were examined using restricted cubic splines within Cox-proportional hazard models, adjusted for a range of cardiovascular and lifestyle related risk factors. Over 15 years of follow-up, 601 (41.9%) women died, with 236 deaths (16.4%) due to CVD. Compared to women with the lowest vitamin K1 intakes (Quartile 1, median 49.1 µg/day), those with the highest intakes (Quartile 4, median 119.3 µg/day) had lower relative hazards for all-cause mortality (HR 0.66 95%CI 0.51-0.86) and CVD mortality (HR 0.61 95%CI 0.41-0.92). A plateau in the inverse association was observed from vitamin K1 intakes of approximately ≥80 µg/day. CONCLUSION: Higher vitamin K1 intakes were associated with lower risk for both all-cause and CVD mortality in community-dwelling older women, independent of CVD related risk factors. A higher intake of vitamin K1 rich foods, such as leafy green vegetables, may support cardiovascular health.

Reduction of neutral lipid reservoirs, bioconversion and untargeted metabolomics reveal distinct roles for vitamin K isoforms on lipid metabolism.

Vitamin K isoforms are known as co-factors for the synthesis of blood-clotting proteins, but several other bioactivities were reported. In this work, we isolated a vitamin K1-analogue (OH-PhQ) from the cyanobacterium Tychonema sp. LEGE 07196 with lipid reducing activity. OH-PhQ reduced neutral lipid reservoirs with an EC50 value of 31 µM after 48 h exposure in zebrafish larvae, while other vitamin K isoforms had EC50 values of 21.1 µM (K2) and 1.2 µM (K3). No lipid reducing activity was observed for K1 up to 50 µM. The presence of vitamin K isoforms was studied in zebrafish after exposure (OH-PhQ, K1, K2 and K3), and a clear preference for bioconversion was observed to retain K1 and OH-PhQ. Untargeted metabolomics revealed different biological effects for vitamin K isoforms on the subclass and metabolite level, but similarities were present on the compound class level, particularly on the regulation of glycerophospholipids. Our data showed for the first time a lipid reducing activity of OH-PhQ and performed a comparative analysis of vitamin K isoforms, which could be important for the development of future nutraceuticals or food supplements.

Rodenticide poisoning leading to cerebral hemorrhage: A case report.

RATIONALE: Anticoagulant rodenticides (ARs) are a substantial fraction of murine types. AR poisoning causes bleeding from the skin, mucous membranes, and multiple organs. However, reports of AR-induced cerebral hemorrhage are scarce. PATIENT CONCERNS: A 40-year-old male presented with dizziness, headache, and limb weakness for 5 days and with coagulopathy. Two days prior to the onset of these symptoms, the patient was exposed to dead mice. DIAGNOSES: Rodenticide intoxication-induced cerebral hemorrhage. INTERVENTIONS: Vitamin K1 infusion, administration of dehydrating agents to reduce intracranial pressure, and correction of acid-base and electrolyte imbalances. OUTCOMES: After 9 days of treatment, the patient's symptoms were relieved, and reexamination revealed that coagulation parameters returned to normal levels. The patient was eventually discharged for observation with oral vitamin K1. CONCLUSIONS: Rodenticide poisoning can lead to intracerebral hemorrhage, and treatment with vitamin K1 infusion is effective. LESSON: Rodenticide poisoning-induced cerebral hemorrhage is rarely reported. Because its symptoms are nonspecific, it is easy to miss the diagnosis or misdiagnose. When patients present with direct and indirect symptoms such as dizziness, headache, and limb weakness, rodenticide poisoning should be considered. Coagulation function and head computed tomography or magnetic resonance imaging examination should be performed at the earliest to confirm the diagnosis and provide timely treatment.

Vitamin K converting enzyme UBIAD1 plays an important role in osteogenesis and chondrogenesis in mice.

Dietary vitamin K1 (phylloquinone: PK) and menaquinone (MK-n) are converted to menadione (MD) in the small intestine and then translocated to various tissues where they are converted to vitamin K2 (menaquinone-4: MK-4) by UbiA prenyltransferase domain containing protein 1 (UBIAD1). MK-4 is effective in bone formation and is used to treat osteoporosis in Japan. UBIAD1 is expressed in bone and osteoblasts and shows conversion to MK-4, but the role of UBIAD1 in osteogenesis is unknown. In this study, we investigated the function of UBIAD1 in osteogenesis using a tamoxifen-dependent UBIAD1-deficient mouse model. When UBIAD1 deficiency was induced from the first week of life, the femur was significantly shortened, and bone mineral density (BMD) was reduced. In addition, the expression of bone and chondrocyte matrix proteins and chondrocyte differentiation factors was significantly decreased. In primary cultured chondrocytes, chondrocyte differentiation was significantly reduced by UBIAD1 deficiency. These results suggest that UBIAD1 is an important factor for the regulation of chondrocyte proliferation and differentiation during osteogenesis.

Tocopherol and phylloquinone biosynthesis in chloroplasts requires the phytol kinase VITAMIN E PATHWAY GENE5 (VTE5) and the farnesol kinase (FOLK).

Chlorophyll degradation causes the release of phytol, which is converted into phytyl diphosphate (phytyl-PP) by phytol kinase (VITAMIN E PATHWAY GENE5 [VTE5]) and phytyl phosphate (phytyl-P) kinase (VTE6). The kinase pathway is important for tocopherol synthesis, as the Arabidopsis (Arabidopsis thaliana) vte5 mutant contains reduced levels of tocopherol. Arabidopsis harbors one paralog of VTE5, farnesol kinase (FOLK) involved in farnesol phosphorylation. Here, we demonstrate that VTE5 and FOLK harbor kinase activities for phytol, geranylgeraniol, and farnesol with different specificities. While the tocopherol content of the folk mutant is unchanged, vte5-2 folk plants completely lack tocopherol. Tocopherol deficiency in vte5-2 plants can be complemented by overexpression of FOLK, indicating that FOLK is an authentic gene of tocopherol synthesis. The vte5-2 folk plants contain only ∼40% of wild-type amounts of phylloquinone, demonstrating that VTE5 and FOLK both contribute in part to phylloquinone synthesis. Tocotrienol and menaquinone-4 were produced in vte5-2 folk plants after supplementation with homogentisate or 1,4-dihydroxy-2-naphthoic acid, respectively, indicating that their synthesis is independent of the VTE5/FOLK pathway. These results show that phytyl moieties for tocopherol synthesis are completely but, for phylloquinone production, only partially derived from geranylgeranyl-chlorophyll and phytol phosphorylation by VTE5 and FOLK.

Dietary Vitamin K1 Intake and Incident Aortic Valve Stenosis.

BACKGROUND: Leaflet calcification contributes to the development and progression of aortic valve stenosis. Vitamin K activates inhibitors of vascular calcification and may modulate inflammation and skeletal bone loss. Therefore, we aimed to determine whether higher dietary intakes of vitamin K1 are associated with a lower incidence of aortic stenosis. METHODS: In the Danish Diet, Cancer and Health study, participants aged 50 to 64 years completed a 192-item food frequency questionnaire at baseline, from which habitual intakes of vitamin K1 were estimated. Participants were prospectively followed using linkage to nationwide registers to determine incident aortic valve stenosis (primary outcome) and aortic stenosis with subsequent complications (aortic valve replacement, heart failure, or cardiovascular disease-related mortality; secondary outcome). RESULTS: In 55 545 participants who were followed for a maximum of 21.5 years, 1085 were diagnosed with aortic stenosis and 615 were identified as having subsequent complications. Participants in the highest quintile of vitamin K1 intake had a 23% lower risk of aortic stenosis (hazard ratio, 0.77 [95% CI, 0.63-0.94]) and a 27% lower risk of aortic stenosis with subsequent complications (hazard ratio, 0.73 [95% CI, 0.56-0.95]), compared with participants in the lowest quintile after adjusting for demographics and cardiovascular risk factors. CONCLUSIONS: In this study, a high intake of vitamin K1-rich foods was associated with a lower incidence of aortic stenosis and a lower risk of aortic stenosis with subsequent complications.

Relação entre ingestão de vitamina K, gordura corporal, perfil lipídico e homeostase da glicose em adultos e idosos / Relationship between vitamin K intake, body fat, lipid profile and glucose homeostasis and in adults and elderly

Introdução: Especula-se que exista uma possível relação entre a ingestão de vitamina K e a diminuição da gordura corporal. Além disso, embora os resultados permaneçam controversos, há um número crescente de estudos que apoiam um papel chave dessa vitamina na melhora do perfil lipídico, da sensibilidade à insulina e na redução do risco de diabetes mellitus tipo 2, contudo pouco se sabe sobre quais mecanismos estariam envolvidos. Objetivo: Investigar as relações entre a ingestão de vitamina K (na forma de filoquinona - PK), gordura corporal, perfil lipídico e marcadores da homeostase da glicose em adultos e idosos. Métodos: Estudo transversal com 298 indivíduos de ambos os sexos, participantes do inquérito ISA - Capital 2015. Amostras de sangue foram coletadas para determinação do perfil lipídico, glicemia de jejum e concentrações de insulina; e índice de estimativa de resistência à insulina (HOMAIR), índice de estimativa da função de células β-pancreáticas (HOMA-β) e índice de estimativa da sensibilidade à insulina (QUICKI) foram calculados. A ingestão de vitamina K foi avaliada por meio de um recordatório alimentar de 24hrs (repetido em 75% da amostra), e a investigação quantitativa da massa gorda foi conduzida por meio da absorciometria de feixe duplo (DXA). Indivíduos com ingestão de vitamina K inferior aos valores de AI foram divididos em subgrupos de acordo com o estado nutricional e faixa etária. Foi realizada a Correlação de Spearman em grupos estratificados de acordo com o Índice de Massa Corporal (IMC) e com o Índice de Gordura Corporal (IGC). Para avaliar as associações entre a ingestão de vitamina K e cada uma das medidas bioquímicas e de adiposidade, foi realizada a regressão linear múltipla. Resultados: Dentre os avaliados, 46% eram do sexo masculino (n=136), com idade mediana de 61 anos (20 - 94 anos), e 56,4% apresentavam sobrepeso ou obesidade (n=168). A mediana de ingestão de vitamina K foi de 102,7 μg, ou 59,9 μg,/1000 kcal, sem diferença de acordo com sexo ou idade. A ingestão de vitamina K apresentou correlação negativa com o HOMA-IR (r = -0,603; p = 0,0134) e correlação positiva com QUICKI (r = 0,603; p = 0,0134) entre os adultos eutróficos do sexo masculino (n = 16). Em idosas com baixo peso (n = 12), a ingestão de vitamina K foi negativamente correlacionada com o Colesterol Total (CT) (r = -0,644; p = 0,0443). Entre as mulheres com elevado IGC e ingestão de vitamina K inferior aos valores de AI (n = 117), foram observadas correlações negativas entre a ingestão de vitamina K e HOMA-IR (r = -0,187; p = 0,0451) e correlações positivas com QUICKI (r = 0,187; p = 0,0451). Conclusões: Os resultados encontrados sugerem uma possível relação entre a ingestão dietética de filoquinona, gordura corporal, perfil lipídico e marcadores da homeostase da glicose, em amostra de adultos e idosos

Introduction: Recent research have investigated a possible inverse relationship between vitamin K intake and body fat. In addition, although the results remain controversial, there is an increasing number of studies supporting a key role of this vitamin in improving lipid profile, insulin sensitivity and reducing the risk of type 2 diabetes mellitus, but little is known about what mechanisms would be involved. Objective: To investigate the relationship between vitamin K intake (in the form of phylloquinone - PK), body fat, lipid profile and markers of glucose homeostasis in adults and elderly. Methods: Cross-sectional study with 298 individuals of both sexes, participants in the ISA - Capital 2015 survey. Blood samples were collected for determination of lipid profile, fasting glycemia and insulin concentrations, and homeostasis model assesment estimate for insulin resistance (HOMA-IR), homeostasis model assessment estimate for β-cell function (HOMA-β) and the quantitative insulin sensitivity check index (QUICKI) were calculate accordingly. Vitamin K intake was assessed by a 24-hour dietary recall (repeated in 75% of the sample) and quantitative investigation of fat mass was conducted using dual-energy x-ray absorptiometry (DXA). Subjects with vitamin K intake lower than AI values were divided into subgroups according to nutritional status and age group. Spearman correlation was performed in stratified groups according to Body Mass Index (BMI) and Fat Mass Index (FMI). To evaluate the associations between vitamin K intake and each of the biochemical and adiposity measures, multiple linear regression were performed. Results: Among the sample, 46% were male (n = 136), with a median age of 61 years (20 - 94 years), and 56.4% were overweight or obese (n= 168). The median vitamin K intake was 102.7 μg, or 59.9 μg, / 1000 kcal, with no difference according to sex or age. Vitamin K intake presented negative correlation with HOMA-IR (r = -0.603; p = 0.0134) and positive correlation with QUICKI (r = 0.603; p=0.0134) among normal weight male adults (n=16). In underweight elderly women (n=12), vitamin K intake was negatively correlated with total cholesterol (TC) (r = -0.644, p = 0.0443). Among females with high FMI and vitamin K intake lower than AI values (n=117), vitamin K intake was negatively correlated with HOMA-IR (r = -0.187; p = 0.0451) and positively correlated with QUICKI (r 12 = 0.187; p = 0.0451). Conclusions: Results suggest a possible relationship between dietary intake of phylloquinone, body fat, lipid profile and glucose homeostasis, among a sample of adults and elderly

Vitamin K: content in food consumed in São Paulo, Brazil

ABSTRACT Recent research on Vitamin K has shown its importance in maintaining vascular and bone health. Brazilian food composition tables do not show phylloquinone content in national foods. These data are needed to obtain more reliable results in nutritional status assessment studies of individuals in relation to this vitamin as studies have shown a geographical influence in food phylloquinone content. This study aims to determine phylloquinone (Vitamin K1) levels in its most important source: dark green leaved vegetables. Several varieties of vegetables were purchased directly from CEAGESP (General Warehouse Company of São Paulo) at different times. Phylloquinone was extracted using organic solvents and quantified by High Performance Liquid Chromatography - HPLC. Results show the concentrations of phylloquinone in commonly consumed foodstuffs. In general, results showed variations with data from literature on the amount of Vitamin K in the plants analysed.

Intoxicaciones con rodenticidas superwarfarínicos / Superwarfarin rodenticide poisoning

Introducción: en la actualidad existe utilización masiva de rodenticidas y su venta no está restringida al público. Las etiologías de intoxicación por estos agentes son variadas pudiendo ser de tipo intencional o accidental. Objetivo: analizar estudios realizados en torno a intoxicaciones con rodenticidas superwarfarínicos en humanos con el propósito de reunir información que oriente a un adecuado tratamiento. Metodología: se realizó una revisión integradora en las bases de datos electrónicas PubMed, TripDataBase, Cochrane, además de Google Scholar y SciELO, libros de divulgación científica, documentos de convenciones, páginas web de instituciones públicas, privadas y artículos vinculados a efectos, cuadro clínico y tratamiento de exposiciones a rodenticidas en seres humanos. Se analizaron los documentos y la información se organizó en tres temáticas: toxicidad de los rodenticidas superwarfarínicos, cuadro clínico y tratamiento médico, y rodenticidas no anticoagulantes disponibles en Chile. Resultados: la dosis tóxica mínima reportada en adultos es de 1 mg de principio activo; en pacientes pediátricos ingestas accidentales rara vez producen síntomas. Los síntomas se observan de forma tardía y su toxicidad es variable. El examen de elección es el International Normalized Ratio (INR) y se realiza en todo paciente con factores de riesgo presentes. El antídoto no se administra de forma profiláctica y la dosis se ajusta individualmente. Conclusión: en niños las ingestas accidentales no son riesgosas por lo que pueden ser observados en el hogar. Pacientes con ingestas masivas requieren controles de INR por meses por lo que es importante que posterior al alta médica exista una óptima coordinación con nivel primario de atención.

Introduction: Currently there is a widespread use of rodenticides, unrestricted to the public. The exposure to these agents may varied being intentional or accidental. Objective: To analyze studies about superwarfarin poisoning in humans, with the purpose of gathering information to guide proper treatment. Methodology: It was conducted an integrative review in the electronic databases PubMed, TripDataBase, Cochrane, Google Scholar and SciELO, science books (reference textbooks), convention documents, websites from public and private institutions and articles about the effects, clinical manifestations and treatment of human exposures to rodenticides. Documents were analyzed and the information organized into three themes: superwarfarin toxicity, clinical features and medical treatment, and non-anticoagulant rodenticides available in Chile. Results: In adults, the minimum dose reported to cause toxicity is 1 mg of active ingredient. In pediatric patients, accidental intakes rarely produce symptoms. The symptoms of poisoning are usually delayed and its toxicity is variable. The test of choice is International Normalized Ratio (INR) and it is performed in all patients with risk factors. The antidote must not be administered prophylactically and the dose is adjusted individually. Conclusions: Accidental intakes in children are not risky and they can be observed at home. Patients with massive intakes require INR monitoring for months so, it is important that an optimal coordination with primary care facilities still exists after medical discharge.

A Study about the Cause and Clinicopathologic Findings of Injection-Induced Dermatitis

BACKGROUND: Cases of dermatitis induced by the injection of certain drugs have been reported. OBJECTIVE: The aim of this study was to assess the cause and clinicopathologic findings of injection-induced dermatitis, and to reveal whether the reaction has any relation to the patient's age, injection site, drug concentration, and time interval from the injection to the occurrence of the skin lesion. METHODS: In this study, we enrolled 10 patients who developed erythematous skin lesions after the injection of causative drugs. The lesions were compared to each other according to the injection site, time interval from the injection to the occurrence of the skin lesion, and clinical characteristics. We performed intradermal and patch tests in each patient with different concentrations of causative drugs. RESULTS: The most common causative drugs were diclofenac and vitamin K1. The eczematous type was the most frequent clinical type. The intradermal test showed more positive results than the patch test. The patch tests with diclofenac (as is, 2.5%, 5%, and 10%) and vitamin K1 (10%) were all negative in 10 patients. Furthermore, intradermal tests with diclofenac (as is) and vitamin K1 (0.1%, 1%, and 10%) were performed in 8 patients. Six patients had a positive reaction, consisting of erythema, induration, and vesiculation, after 1 and 2 days. CONCLUSION: Our results showed that the most common causative agents were diclofenac and vitamin K1. Moreover, it seems that that intradermal test is more useful than the patch test in the diagnosis of injection-induced dermatitis.