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1.
BMJ Open Qual ; 13(Suppl 1)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589043

RESUMO

BACKGROUND: Early skin-to-skin contact (SSC) at birth has been shown to improve neonatal outcomes due to enhanced cardiorespiratory stability, thermoregulation and breastfeeding success. LOCAL PROBLEM: The practice of early SSC was virtually non-existent in our delivery room (DR). METHODS AND INTERVENTIONS: The study was conducted in a newly established tertiary care teaching hospital in Western Rajasthan, India. We aimed to improve the median duration of early SSC from 0 min to at least 60 min over 24 weeks in our DR. A quality improvement (QI) team was formed, and all inborn infants ≥35 weeks born vaginally from 9 March 2017 were included. Using the tools of point-of-care QI, we found the lack of standard operating procedure, lack of knowledge among nursing staff regarding early SSC, routine shifting of all infants to radiant warmer, the practice of prioritising birthweight documentation and vitamin K administration as the major hindrances to early SSC. Various change ideas were implemented and tested sequentially through multiple plan-do-study-act (PDSA) cycles to improve the duration of early SSC. Interventions included framing a written policy for SSC, sensitising the nursing staff and resident doctors, actively delaying the alternate priorities, making early SSC a shared responsibility among paediatricians, obstetricians, nursing staff and family members, and continuing SSC in the recovery area of the DR complex. RESULTS: The duration of early SSC increased from 0 to 67 min without any additional resources. The practice of SSC got well established in the system as reflected by a sustained improvement of 63 min and 72 min, respectively, at the end of 2 months and 4 years after study completion. CONCLUSION: Using the QI approach, we established and sustained the practice of early SSC for more than 60 min in our unit by using system analysis and testing change ideas in sequential PDSA cycles.


Assuntos
Método Canguru , Melhoria de Qualidade , Recém-Nascido , Lactente , Criança , Humanos , Gravidez , Feminino , Método Canguru/métodos , Índia , Vitamina K , Fatores de Tempo
2.
Rinsho Ketsueki ; 65(3): 164-168, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38569860

RESUMO

Congenital protein C (PC) deficiency is one type of hereditary thrombosis. Patients with hereditary thrombosis are at high risk for thrombosis in the perioperative period, but a standard management strategy has not been established. Here we report a case of perioperative management of a fracture in a child with homozygous congenital PC deficiency. The patient was a 3-year-old boy who was diagnosed with congenital PC deficiency at birth. He sustained a traumatic supracondylar fracture of the right humerus and underwent emergency surgery. To prepare for open surgery for fixation of the fracture, warfarin was discontinued, and an activated PC (APC) concentrate was used in combination with vitamin K antagonism. However, warfarin was administered during the scheduled nail extraction because the operation was minimally invasive. No thrombotic or bleeding complications occurred in either operation. In emergency surgery in patients with congenital PC deficiency, the combination of vitamin K and APC concentrate is considered a maintenance option for PC deficiency. Postoperative PT-INR control was difficult in our patient due to the administration of vitamin K and withdrawal of warfarin, and this issue must be addressed in the future. Further case experience is desirable to standardize perioperative management.


Assuntos
Fraturas Ósseas , Deficiência de Proteína C , Trombose , Pré-Escolar , Humanos , Recém-Nascido , Masculino , Anticoagulantes , Fraturas Ósseas/complicações , Deficiência de Proteína C/complicações , Trombose/complicações , Vitamina K , Varfarina/uso terapêutico
3.
Nefrología (Madrid) ; 44(2): 268-275, Mar-Abr. 2024. tab, ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-231577

RESUMO

La fibrilación auricular (FA) es la arritmia crónica más frecuente en pacientes con enfermedad renal crónica (ERC). La anticoagulación oral con antagonistas de la vitamina K (AVK) y actualmente los anticoagulantes orales de acción directa (ACOD) han sido el pilar fundamental para la prevención de eventos tromboembólicos. Sin embargo, no existen ensayos clínicos aleatorizados de su perfil riesgo-beneficio en pacientes con ERC estadio 5 en diálisis peritoneal (DP) y son pocas las evidencias en la literatura sobre esta población. El objetivo del estudio fue conocer la prevalencia, tratamiento y profesionales implicados en el manejo de la FA en DP en nuestro entorno mediante el análisis descriptivo de una encuesta enviada a diferentes unidades de DP de España. Se incluyeron en el estudio 1.403 pacientes en programa de DP, de los cuales 186 (13,2%) presentaban FA no valvular (FANV). Además, observamos que la valoración de los scores para el inicio del tratamiento anticoagulante la realizaba mayoritariamente el cardiólogo (60% de los centros), así como la prescripción de anticoagulación (cardiólogo 47% o en conjunto con el nefrólogo 43%). En conclusión, los pacientes en DP presentan una notable prevalencia de FANV. Reciben frecuentemente anticoagulación oral (ACO) con AVK, así como con ACOD. Los datos obtenidos respecto a las escalas utilizadas para la valoración de riesgo tromboembólico y de sangrado, tratamiento e implicación por parte de Nefrología indican que existe una necesidad de formación e involucramiento del nefrólogo en esta patología.(AU)


Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillar for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population. The objective of our study was to know the prevalence, treatment and professionals involved in the management of atrial fibrillation in peritoneal dialysis patients. For this purpose, we performed a descriptive analysis through a survey sent to different peritoneal dialysis units in Spain. A total of 1403 patients on peritoneal dialysis were included in the study, of whom 186 (13.2%) had non-valvular atrial fibrillation. In addition, the assessment of the scores of thromboembolic and bleeding risks for the indication of oral anticoagulation was mainly carried out by the cardiologist (60% of the units), as well as its prescription (cardiologist 47% in consensus with the nephrologist 43%). In summary, patients on peritoneal dialysis have a remarkable prevalence of non-valvular atrial fibrillation. Patients frequently receive oral anticoagulation with vitamin K antagonists, as well as direct oral anticoagulants. The data obtained regarding the scales used for the assessment of thromboembolic and bleeding risk, treatment and involvement by Nephrology indicates that there is a need for training and involvement of the nephrologist in this pathology.(AU)


Assuntos
Humanos , Masculino , Feminino , Fibrilação Atrial/tratamento farmacológico , Prevalência , Diálise Peritoneal , Vitamina K , Inibidores do Fator Xa , Avaliação de Sintomas , Nefrologia , Nefropatias , Estudos Transversais , Estudos Retrospectivos
4.
Vopr Pitan ; 93(1): 92-102, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38555613

RESUMO

The influence of a stress factor, widespread in modern conditions, on the vitamin status has not been studied enough. At the same time, the negative stress impact can be aggravated against the background of unhealthy nutrition, which in turn affects the vitamin status of the organism. In this regard, the goal of the research was to evaluate the effect of chronic restrict stress on the vitamin supply in rats fed a diet with adequate and increased content of fat, sugar and cholesterol. Material and methods. The experiment was carried out on 37 growing male Wistar rats (initial body weight of 45±5 g) divided into 4 groups. Animals of the 1st (control) and the 2nd groups received a complete semi-synthetic diet (CSSD) (20% protein, 10% fat, 58% carbohydrates in the form of starch, 384 kcal/100 g) for 92 days. The levels of all vitamins and mineral elements in the rats' diets were adequate for growing rats. Rats of the 3rd and the 4th groups were fed a high-calorie, high-fat high-carbohydrate diet (HFHCD) (20% protein, 28% fat, 2% cholesterol, 18% carbohydrates in the form of starch, 20% sucrose, 511 kcal/100 g). Animals of groups 2 and 4 were subjected to daily 90-minute immobilization. The concentration of vitamins A (retinol and retinol palmitate) and E (α-tocopherol) in the blood serum and liver were determined by high-performance liquid chromatography, vitamins B1 and B2 in the liver and urine, as well as riboflavin in the blood serum and 4-pyridoxic acid (4-PA) in urine were determined by fluorimetric methods. Biochemical parameters of blood serum were determined on a biochemical analyzer; the total content of fat, triglycerides (TG) and cholesterol (CH) was determined in the liver. Results. Replacing CSSD with HFHCD, both under restraint stress and without, was accompanied by an increase in liver weight by 1.8-2.0 fold, in its fat content by 2.6-3.3 fold, cholesterol by 32.6-35.3 fold and TG - by 33.0-57.6 fold (p=<0.001). An increase in alanine aminotransferase (ALT) activity by 1.7-2.0 fold (p=<0.01), in low-density lipoprotein (LDL) cholesterol level by 5.4 fold (p=<0.05) and the atherogenic coefficient by 2.5 fold (p<0.01) as well as a decrease in creatinine and urea level (p=<0.05) in blood serum were revealed. Immobilization was accompanied by a decrease in body weight, liver and liver fat in rats fed both CSSD and HFHCD (p<0.05), but didn't affect the blood serum biochemical parameters, with the exception of an increase in ALT activity. If the activity of alkaline phosphatase (ALP) did not change during immobilization of rats fed the CSSD, then in animals fed the high-calorie diet it decreased by 37.5% (p=<0.05 from the control) under its increase against the background of restrict stress by 78.7% (p=<0.01) compared to the indicator of rats of the 3rd group. Immobilization of rats treated with CSSD was accompanied by an increase in both absolute serum α-tocopherol level and concentration correlated with the level of cholesterol and triglycerides by 26.0-57.5% (p<0.05), with a simultaneous decrease in its content in the liver per 1 g of wet tissue by 22.1% (p=0.041) relative to the indicators of intact animals. Immobilization reduced the level of retinol palmitate in the liver by 2.3 times (p<0.01), but did not affect retinol level in the blood serum. At the same time, indicators of B vitamin status (the content of vitamins B1 and B2 in the liver per 1 g of wet tissue and per organ, blood serum riboflavin level, urinary excretion of riboflavin and 4-PA) did not change, with the exception of thiamine urinary excretion, which reduced compared to the control by 38.8%. In rats fed HFHCD, immobilization had no additional effect on the supply with vitamins A and E. The content of vitamins B1 and B2 in the liver in terms of the whole organ was reduced by 14.0-26.7% relative to the indicator in animals of the 3rd group, not subjected to chronic stress, only due to differences in liver weight in animals of these groups. Conclusion. The data obtained indicate that chronic stress has a negative effect on the vitamin status of the body, worsening the supply with vitamins A, E and B1, and substantiate the feasibility of studying the mechanisms of this effect in order to develop effective vitamin complexes for the treatment and prevention of diseases caused by long-term stress.


Assuntos
Diterpenos , Ésteres de Retinil , Vitamina A , Complexo Vitamínico B , Ratos , Masculino , Animais , alfa-Tocoferol , Ratos Wistar , Tiamina , Riboflavina , Complexo Vitamínico B/metabolismo , Triglicerídeos/metabolismo , Fígado/metabolismo , Vitamina K/metabolismo , Dieta , Colesterol , Carboidratos , Peso Corporal , Amido/metabolismo
5.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473850

RESUMO

Free radicals (FRs) are unstable molecules that cause reactive stress (RS), an imbalance between reactive oxygen and nitrogen species in the body and its ability to neutralize them. These species are generated by both internal and external factors and can damage cellular lipids, proteins, and DNA. Antioxidants prevent or slow down the oxidation process by interrupting the transfer of electrons between substances and reactive agents. This is particularly important at the cellular level because oxidation reactions lead to the formation of FR and contribute to various diseases. As we age, RS accumulates and leads to organ dysfunction and age-related disorders. Polyphenols; vitamins A, C, and E; and selenoproteins possess antioxidant properties and may have a role in preventing and treating certain human diseases associated with RS. In this review, we explore the current evidence on the potential benefits of dietary supplementation and investigate the intricate connection between SIRT1, a crucial regulator of aging and longevity; the transcription factor NRF2; and polyphenols, vitamins, and selenium. Finally, we discuss the positive effects of antioxidant molecules, such as reducing RS, and their potential in slowing down several diseases.


Assuntos
Antioxidantes , Selênio , Humanos , Antioxidantes/farmacologia , Vitaminas/farmacologia , Selênio/farmacologia , Polifenóis/farmacologia , Estresse Oxidativo , Vitamina A/farmacologia , Vitamina K/farmacologia , Espécies Reativas de Oxigênio/farmacologia
6.
Nutrients ; 16(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38474744

RESUMO

Vascular calcification (VC) is a consequence of chronic kidney disease (CKD) which is of paramount importance regarding the survival of CKD patients. VC is far from being controlled with actual medication; as a result, in recent years, diet modulation has become more compelling. The concept of medical nutritional therapy points out the idea that food may prevent or treat diseases. The aim of this review was to evaluate the influence of food habits and nutritional intervention in the occurrence and progression of VC in CKD. Evidence reports the harmfulness of ultra-processed food, food additives, and animal-based proteins due to the increased intake of high absorbable phosphorus, the scarcity of fibers, and the increased production of uremic toxins. Available data are more supportive of a plant-dominant diet, especially for the impact on gut microbiota composition, which varies significantly depending on VC presence. Magnesium has been shown to prevent VC but only in experimental and small clinical studies. Vitamin K has drawn considerable attention due to its activation of VC inhibitors. There are positive studies; unfortunately, recent trials failed to prove its efficacy in preventing VC. Future research is needed and should aim to transform food into a medical intervention to eliminate VC danger in CKD.


Assuntos
Insuficiência Renal Crônica , Calcificação Vascular , Animais , Humanos , Insuficiência Renal Crônica/metabolismo , Calcificação Vascular/metabolismo , Fósforo/metabolismo , Vitamina K/uso terapêutico , Alimentos
7.
J Nucl Med Technol ; 52(1): 15-20, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443112

RESUMO

Chronic functional gallbladder disorder, characterized by biliary pain in the absence of structural pathology, poses a diagnostic challenge necessitating reliable cholecystagogues for accurate evaluation. However, recurrent shortages of synthetic cholecystokinin analogs have prompted the exploration of alternative agents. This paper describes the efficacy of Ensure Plus as a viable fatty meal substitute for hepatobiliary scintigraphy in assessing chronic functional gallbladder disorder. Through comparative studies, Ensure Plus demonstrates comparable diagnostic accuracy to cholecystokinin in similar patient populations. Furthermore, Ensure Plus demonstrates significant symptom improvement after cholecystectomy in patients with anomalous gallbladder ejection fractions. This paper offers a detailed protocol for the seamless integration of Ensure Plus into hepatobiliary scintigraphy, providing clinicians with a valuable tool to navigate cholecystokinin shortages while maintaining diagnostic precision in cases of chronic functional gallbladder disorder. The use of Ensure Plus not only addresses practical supply challenges but also underscores its potential as a cost-effective and clinically sound alternative in biliary diagnostics.


Assuntos
Doenças da Vesícula Biliar , Vitamina K , Humanos , Doenças da Vesícula Biliar/diagnóstico por imagem , Colecistocinina , Cintilografia
8.
PLoS One ; 19(3): e0298596, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451960

RESUMO

BACKGROUND: The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice. METHODS: Cohorts were created using electronic healthcare databases from the UK, the Netherlands, Germany and Sweden. Patients with a first prescription of rivaroxaban or vitamin K antagonist during the period from December 2011 (in the UK, January 2012) to December 2017 (in Germany, December 2016) for venous thromboembolism indication, with no record of atrial fibrillation or recent cancer history, were observed until the occurrence of each safety outcome (hospitalization for intracranial, gastrointestinal, urogenital or other bleeding), death or study end (December 2018; in Germany, December 2017). Crude incidence rates of each outcome per 100 person-years were computed. RESULTS: Overall, 44 737 rivaroxaban and 45 842 vitamin K antagonist patients were enrolled, mean age, 59.9-63.8 years. Incidence rates were similar between rivaroxaban and vitamin K antagonist users with some exceptions, including higher incidence rates for gastrointestinal bleeding in rivaroxaban users than in vitamin K antagonist users. Among rivaroxaban users, mortality and bleeding risk generally increased with age, renal impairment and diabetes. CONCLUSIONS: This study provides further data from routine clinical practice that broadly support safety profile of rivaroxaban for VTE indication and complement findings from previous randomized clinical trials.


Assuntos
Fibrilação Atrial , Tromboembolia Venosa , Humanos , Pessoa de Meia-Idade , Rivaroxabana/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Fibrinolíticos/uso terapêutico , Vitamina K , Inibidores do Fator Xa/efeitos adversos
9.
Ned Tijdschr Geneeskd ; 1682024 01 29.
Artigo em Holandês | MEDLINE | ID: mdl-38525862

RESUMO

OBJECTIVE: To investigate whether frail elderly people with atrial fibrillation (AF) who are currently using a vitamin K antagonist (VKA) should be switched to a direct-acting oral anticoagulant (DOAC). DESIGN: Randomized clinical trial. METHODS: 662 frail elderly AF patients were switched to a DOAC, and 661 patients continued their VKA. The primary endpoint was a major or clinically relevant non-major bleeding during 1 year of follow-up. Secondary endpoints included thrombo-embolic events. RESULTS: The mean age of the included patients was 83 years. In the 'switch to DOAC arm', 101 bleeding events (15.3%) occurred and in the 'continue with VKA arm', 62 bleeding events (9.4%); an increase of 69% more bleeding events (P-value 0.001). The number of thrombo-embolic events was not significantly different between both groups. CONCLUSION: Switching from a VKA to a DOAC in frail elderly people with AF leads to 69% more bleeding, without a difference in thrombo-embolic events.


Assuntos
Anticoagulantes , Fibrilação Atrial , Cumarínicos , Idoso , Idoso de 80 Anos ou mais , Humanos , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Cumarínicos/efeitos adversos , Idoso Fragilizado , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Vitamina K
10.
Nutrients ; 16(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38542745

RESUMO

Zinc, magnesium, and vitamin K are important nutrients for humans. There are various factors that contribute to the development of their deficiency, which might result in or exacerbate various diseases. These nutrients can also interact with vitamin D metabolism and activity. This review discusses the main aspects of zinc, magnesium and vitamin K metabolism and action in the body, their clinical significance, and the "crosstalk" with vitamin D, as well as providing general suggestions for clinical practice when supplementation with these nutrients might be useful, in addition to vitamin D supplementation.


Assuntos
Magnésio , Deficiência de Vitamina D , Humanos , Zinco , Vitamina K , Suplementos Nutricionais , Vitamina D , Deficiência de Vitamina D/tratamento farmacológico
11.
Bioresour Technol ; 398: 130511, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437963

RESUMO

The effect of thiamine (TA), ascorbic acid (AA), citric acid, and gallic acid (GA) on bacterial cellulose (BC) production by Komagataeibacter sucrofermentans, in synthetic (Hestrin and Schramm, HS) and natural substrates (industrial raisins finishing side stream extract, FSSE; orange juice, OJ; green tea extract, GTE), was investigated. The Response Surface Methodology was found reliable for BC yield prediction and optimization. Higher yields were achieved in the FSSE substrates, especially those supplemented with AA, TA, and GA (up to 19.4 g BC/L). The yield in the non-fortified substrates was 1.1-5.4 and 11.6-15.7 g/L, in HS and FSSE, respectively. The best yield in the natural non-fortified substrate FSSE-OJ-GTE (50-20-30 %), was 5.9 g/L. The porosity, crystallinity, and antioxidant properties of the produced BC films were affected by both the substrate and the drying method (freeze- or oven-drying). The natural substrates and the process wastewaters can be further exploited towards added value and sustainability. Take Home Message Sentence: Raisin and citrus side-streams can be efficiently combined for bacterial cellulose production, enhanced by other vitamin- and phenolic-rich substrates such as green tea.


Assuntos
Acetobacteraceae , Celulose , Vitaminas , Celulose/química , Rios , Vitamina A , Vitamina K , Compostos Orgânicos , Meios de Cultura , Chá , Extratos Vegetais
12.
BMC Vet Res ; 20(1): 101, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481237

RESUMO

BACKGROUND: Nutrition has a primary role for optimum expression of genetic potential, and most of the farmers have limited resources of green fodder. Hence, a fat-soluble vitamin, especially vitamin A and E and trace elements remained most critical in the animal's ration and affects their productive and reproductive performance adversely. Animals cannot be able to produce these vitamins in their bodies; hence, an exogenous regular supply is needed to fulfil the physiological needs and to maintain high production performance. This study elucidated effects of antioxidant vitamins (A, D, E) and trace elements (Cu, Mn, Se, Zn) administration on gene expression, metabolic, antioxidants and immunological parameters in dromedary camels during transition period. RESULTS: At 0 day, there were no appreciable differences in the expression patterns of the metabolic (IGF-I, ACACA, SCD, FASN, LPL, and BTN1A1) genes between the control and treatment groups, despite lower levels. A substantial variation in the mRNA levels of SOD1, SOD3, PRDX2, PRDX3, PRDX4, PRDX6, and AhpC/TSA was observed between the control and treatment groups, according to the antioxidant markers. In comparison to the control group, the treatment group displayed a significant up-regulation at 0 and 21 days. The treatment and control groups exhibited substantial differences in the mRNA values of IL-1α, IL-1ß, IL-6, and TNFα, as indicated by immunological markers. In comparison to the control group, there was a noticeable down-regulation in the treatment group at 0 and + 21 days. But IL10 produced the opposite pattern. No significant difference was observed in glucose, cholesterol, triglyceride, HDL, total protein, NEFA, BHBA, cortisol and IGF-1 levels between control and treatment group. The activity of serum GPx, SOD and TAC was significantly affected by time and treatment x time in supplemented groups as compared with control group. IL-1, IL-1, IL-6, and TNF were noticeably greater in the control group and lower in the treatment group. Additionally, in all groups, the concentration of all pro-inflammatory cytokines peaked on the day of delivery and its lowest levels showed on day 21 following calving. The IL-10 level was at its peak 21 days prior to calving and was lowest on calving day. CONCLUSION: The results demonstrated a beneficial effect of antioxidant vitamins and trace elements on the metabolic, antioxidant and immunological markers in dromedary camels throughout their transition period.


Assuntos
Oligoelementos , Animais , Oligoelementos/farmacologia , Antioxidantes/metabolismo , Vitaminas/farmacologia , Camelus , Vitamina A/farmacologia , Interleucina-6 , Vitamina K , Zinco , RNA Mensageiro , Expressão Gênica , Interleucina-1
13.
J Pediatr Gastroenterol Nutr ; 78(3): 677-684, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38504391

RESUMO

OBJECTIVES: Micronutrient deficiencies characterize classical "late-diagnosed" celiac disease (CeD). This study aimed to identify the prevalence of micronutrient deficiencies among children with "early-diagnosed" screening-identified CeD to determine the clinical value of routine testing for deficiencies in those patients. METHODS: A case-control study was conducted on screening-identified CeD patients diagnosed during a mass screening study (84 patients, mean age 11.3 ± 2.6 years). The controls (443 children, mean age 10.8 ± 2.5 years) were negative for celiac disease serological screening. Hemoglobin, serum levels of iron, ferritin, folate, vitamin B12, vitamin A, vitamin E, 25-OH vitamin D, zinc, and selenium were measured. RESULTS: The mean serum levels of hemoglobin, iron, ferritin, vitamin D, zinc, copper, and selenium were significantly lower in CeD patients than in healthy controls (hemoglobin 12.56 vs. 13.02 g/dL [p = 0.04]; iron 10.61 vs. 17.6 µmol/L [p < 0.001], ferritin 25.7 vs. 48.3 µg/L [p < 0.001], vitamin D 29.1 vs. 37.5 nmol/L, zinc 11.9 vs. 21.7 µmol/L, copper 18.9 vs. 32.5 µmol/L, selenium 1.04 vs. 1.36 µmol/L; p < 0.001). Patients with celiac and severe intestinal damage (Marsh IIIb and IIIc) had significantly lower serum ferritin and vitamin A levels than patients with mild intestinal damage (Marsh II and IIIa) (ferritin 15 vs. 22 µg/L, p < 0.025; vitamin A 0.85 vs. 1.35 µmol/L, p = 0.007). CONCLUSION: Micronutrient deficiencies are still detectable in "early-diagnosed" screening-identified CeD cases, a clinically relevant result that strongly supports efforts for screening and early diagnosis of CeD.


Assuntos
Doença Celíaca , Selênio , Criança , Humanos , Adolescente , Vitaminas , Vitamina A , Estudos de Casos e Controles , Cobre , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Micronutrientes , Ferro , Zinco , Vitamina D , Vitamina K , Ferritinas , Hemoglobinas/metabolismo
14.
Int J Mol Sci ; 25(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38542466

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a lack of reliable diagnostic biomarkers. Protein induced by vitamin K absence (PIVKA-II) is a protein increased in various cancers (particularly in hepatocellular carcinoma), and it has recently exhibited superior diagnostic performance in PDAC detection compared to other biomarkers. The aim of our research was to identify an in vitro model to study PIVKA-II production, distribution, and release in PDAC. We examined the presence of PIVKA-II protein in a panel of stabilized pancreatic cancer cell lines by Western blot analysis and indirect immunofluorescence (IFA). After quantitative evaluation of PIVKA-II in PaCa 44, H-Paf II, Capan-1, and PANC-1, we adopted the latter as a reference model. Subsequently, we analyzed the effect of glucose addiction on PIVKA-II production in a PANC-1 cell line in vitro; PIVKA-II production seems to be directly related to an increase in glucose concentration in the culture medium. Finally, we evaluated if PIVKA-II released in the presence of increasing doses of glucose is concomitant with the expression of two well-acknowledged epithelial-mesenchymal transition (EMT) markers (Vimentin and Snail). According to our experimental model, we can speculate that PIVKA-II release by PANC-1 cells is glucose-dependent and occurs jointly with EMT activation.


Assuntos
Carcinoma Hepatocelular , Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Vitamina K , Vitaminas/análise , Biomarcadores , Precursores de Proteínas , Protrombina/análise , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/patologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Neoplasias Hepáticas/patologia , Modelos Teóricos , Glucose , Biomarcadores Tumorais/genética
15.
Int J Mol Sci ; 25(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38542487

RESUMO

One mechanism to regulate pathological vascular calcification (VC) is its active inhibition. Loss or inactivation of endogenic inhibitors is a major inductor of VC. Such inhibitors are proteins rich in gamma-glutamyl residues (Gla-proteins), whose function strongly depends on vitamin K. The current narrative review is focused on discussing the role of extrahepatic vitamin K-dependent Gla-proteins (osteocalcin, OC; matrix Gla-protein, MGP; Gla-rich protein, GRP) in cardio-vascular pathology. Gla-proteins possess several functionally active forms whose role in the pathogenesis of VC is still unclear. It is assumed that low circulating non-phosphorylated MGP is an indicator of active calcification and could be a novel biomarker of prevalent VC. High circulating completely inactive MGP is proposed as a novel risk factor for cardio-vascular events, disease progression, mortality, and vitamin K deficiency. The ratio between uncarboxylated (ucOC) and carboxylated (cOC) OC is considered as an indicator of vitamin K status indirectly reflecting arterial calcium. Despite the evidence that OC is an important energy metabolic regulator, its role on global cardio-vascular risk remains unclear. GRP acts as a molecular mediator between inflammation and calcification and may emerge as a novel biomarker playing a key role in these processes. Gla-proteins benefit clinical practice as inhibitors of VC, modifiable by dietary factors.


Assuntos
Doenças Cardiovasculares , Calcificação Vascular , Humanos , Osteocalcina/metabolismo , Vitamina K , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Calcificação Vascular/complicações , Doenças Cardiovasculares/etiologia , Biomarcadores
16.
Int J Mol Sci ; 25(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38396721

RESUMO

The human Vitamin K Epoxide Reductase Complex (hVKORC1), a key enzyme transforming vitamin K into the form necessary for blood clotting, requires for its activation the reducing equivalents delivered by its redox partner through thiol-disulfide exchange reactions. The luminal loop (L-loop) is the principal mediator of hVKORC1 activation, and it is a region frequently harbouring numerous missense mutations. Four L-loop hVKORC1 mutants, suggested in vitro as either resistant (A41S, H68Y) or completely inactive (S52W, W59R), were studied in the oxidised state by numerical approaches (in silico). The DYNASOME and POCKETOME of each mutant were characterised and compared to the native protein, recently described as a modular protein composed of the structurally stable transmembrane domain (TMD) and the intrinsically disordered L-loop, exhibiting quasi-independent dynamics. The DYNASOME of mutants revealed that L-loop missense point mutations impact not only its folding and dynamics, but also those of the TMD, highlighting a strong mutation-specific interdependence between these domains. Another consequence of the mutation-induced effects manifests in the global changes (geometric, topological, and probabilistic) of the newly detected cryptic pockets and the alternation of the recognition properties of the L-loop with its redox protein. Based on our results, we postulate that (i) intra-protein allosteric regulation and (ii) the inherent allosteric regulation and cryptic pockets of each mutant depend on its DYNASOME; and (iii) the recognition of the redox protein by hVKORC1 (INTERACTOME) depend on their DYNASOME. This multifaceted description of proteins produces "omics" data sets, crucial for understanding the physiological processes of proteins and the pathologies caused by alteration of the protein properties at various "omics" levels. Additionally, such characterisation opens novel perspectives for the development of "allo-network drugs" essential for the treatment of blood disorders.


Assuntos
Mutação de Sentido Incorreto , Vitamina K Epóxido Redutases , Humanos , Mutação , Oxirredução , Vitamina K/metabolismo , Vitamina K Epóxido Redutases/genética , Vitamina K Epóxido Redutases/metabolismo
17.
J Comp Eff Res ; 13(4): e230146, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38415341

RESUMO

Aim: To evaluate the cost-effectiveness of seven screening strategies for chronic hepatitis B (CHB) patients in China. Methods: A discrete event simulation model combining a decision tree and Markov structure was developed to simulate a CHB cohort aged ≥40 years on a lifetime horizon and evaluate the costs and health outcomes (quality-adjusted life years [QALYs] gained) of ultrasonography (US), alpha-fetoprotein (AFP), protein induced by vitamin K absence-II (PIVKA-II), AFP+US, AFP+PIVKA-II, GAAD (a diagnostic algorithm based on gender and age combined with results of AFP and PIVKA-II) and GAAD+US. Epidemiologic, clinical performance, utility and cost data were obtained from the literature, expert interviews and real-world data. Uncertainties on key parameters were explored through deterministic and probabilistic sensitivity analyses (DSA and PSA). Results: Compared with other strategies, GAAD+US detected the most HCC patients at early stage, and GAAD was the screening strategy with the lowest average cost per HCC case diagnosed. Using 3× China's 2022 GDP per capita ($38,233.34) as the threshold, the three strategies of US, GAAD and GAAD+US formed a cost-effectiveness frontier. Screening with US, GAAD, or GAAD+US was associated with costs of $6110.46, $7622.05 and $8636.32, and QALYs of 13.18, 13.48 and 13.52, respectively. The ICER of GAAD over US was $4993.39/QALY and the ICER of GAAD+US over GAAD was $26,691.45/QALY, which was less than 3× GDP per capita. Both DSA and PSA proved the stability of the results. Conclusion: GAAD+US was the most cost-effective strategy for early HCC diagnosis among CHB patients which could be considered as the liver cancer screening scheme for the high-risk population in China.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Masculino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , alfa-Fetoproteínas/metabolismo , Análise de Custo-Efetividade , Antígeno Prostático Específico , Análise Custo-Benefício , China , Anos de Vida Ajustados por Qualidade de Vida , Vitamina K
18.
Food Funct ; 15(6): 2974-2981, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38410907

RESUMO

Background: Dyslipidemia is one of the most common chronic diseases, and is associated with insulin resistance (IR) and inadequate vitamin K intake. We aimed to explore the association between IR, vitamin K intake, and dyslipidemia, and further to explore the mediating role of IR. Materials and methods: 12 860 participants from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018 were included in this study. Insulin resistance was determined by using the homeostatic model assessment for insulin resistance (HOMA-IR). Weighted multiple logistic regression and mediation analyses were conducted to analyze the associations between IR, vitamin K intake, and dyslipidemia. Results: We found that both vitamin K intake-met Dietary Reference Intake (DRI) and non-IR were protective factors of high triglycerides (with ORs (95% CI) of 0.71 (0.57, 0.87) and 0.36 (0.29, 0.45), respectively) and low high-density lipoprotein cholesterol (with ORs (95% CI) of 0.72 (0.62, 0.82) and 0.39 (0.34, 0.41), respectively). IR-related indicators (HOMA-IR and insulin) partly mediated these effects, and the proportion ranged from 16.36% to 18.52%. Conclusion: Vitamin K intake-met DRI and non-IR were associated with lower risk of dyslipidemia including high TG and low HDL-C. IR partly mediated the association of vitamin K intake with high TG and low HDL-C.


Assuntos
Dislipidemias , Resistência à Insulina , Adulto , Humanos , Inquéritos Nutricionais , Insulina , Vitamina K
20.
Eur J Clin Pharmacol ; 80(5): 737-746, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38353692

RESUMO

PURPOSE: To analyze the risk factors influencing the development of cefoperazone-induced coagulopathy in critically ill patients and determine the threshold of serum trough concentration. METHODS: A retrospective case-control study was conducted in the intensive care unit patients treated with cefoperazone, and it was approved by the Ethical Committee of Drum Tower Hospital affiliated with the Medical School of Nanjing University (NO.2023-158-01). Patients were divided into the normal group and coagulopathy group based on prothrombin time. The clinical characteristics of the two groups were compared using univariate analysis. The serum concentration threshold and influencing factors of cefoperazone-induced coagulopathy in critically ill patients were analyzed using the receiver operating characteristic curve and multivariate logistic regression analysis. RESULTS: A total of 113 patients were included, and cefoperazone-induced coagulopathy occurred in 39 patients, with an incidence of 34.5%. These patients experienced significant prothrombin time prolongation around day 6 (median) after cefoperazone application. The serum trough concentration threshold of cefoperazone-induced coagulopathy in critically ill patients was 87.765 mg/l. Multivariate logistic regression analysis revealed that the APACHE II score (p = 0.034), prophylactic use of vitamin K1 (p < 0.001), hepatic impairment (p = 0.014), and Cmin ≥ 87.765 mg/l (p = 0.005) were associated with cefoperazone-induced coagulopathy. CONCLUSION: Cefoperazone-induced coagulopathy usually occurs on the 6th day of cefoperazone use in critically ill patients. The risk will increase in patients with an APACHE II score > 25, hepatic impairment, and cefoperazone Cmin ≥ 87.765 mg/l. Vitamin K1 is effective in preventing this adverse reaction.


Assuntos
Transtornos da Coagulação Sanguínea , Hepatopatias , Humanos , Cefoperazona/efeitos adversos , Estudos de Casos e Controles , Estudos Retrospectivos , Estado Terminal , Fatores de Risco , Transtornos da Coagulação Sanguínea/induzido quimicamente , Vitamina K , Unidades de Terapia Intensiva
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