Inflammation is a key event that is closely associated with the pathophysiology of frailty. The relationship of genetic polymorphisms into inflammatory cytokines with frailty remains poorly ...understood. The aim of this study was to investigate the association between VNTR polymorphisms of the
IL
-
4
and
IL
-
1RN
genes with the risk of frailty. We included a sample of 630 community-dwelling elderly aged 70 and older. Both
IL
-
4
and
IL
-
1RN
VNTR polymorphisms were genotyped by the polymerase chain reaction (PCR) method. Mean age was 77.7 years (SD = 6.0) and 52.5 % were women. The participants classified as frail were more likely to be older, had lower MMSE score (
p
< 0.001), and had more disability for IADL (
p
< 0.001) and ADL (
p
< 0.001). Genotypic and allelic frequencies for the
IL
-
4
VNTR polymorphism did not show significant differences between study groups (
p
> 0.05). However, we just observed a significant difference in the allelic frequencies for the A2 allele of the
IL
-
1RN
VNTR polymorphism between frail and nonfrail groups (OR 1.84, 95 % CI 1.08–3.12,
p
= 0.02). In addition, we analyzed the combined effect of the
IL
-
4
and
IL
-
1RN
VNTR polymorphisms and their possible association with frailty, where the combined
IL
-
4
low
–
IL
-
1Ra
high
genotype was identified as a marker of risk to frailty syndrome (OR 7.86, 95 % CI 1.83–33.69,
p
= 0.006). Our results suggest that both A2 allele and the combined
IL
-
4
low
–
IL
-
1Ra
high
genotype might be genetic markers of susceptibility to frailty in Mexican elderly.
Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. ...Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism.
A retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period.
A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2 ± 0.9 mg/dl y GFR-MDRD was 36 ± 20 ml/min/1.73 m(2). Paricalcitol doses were gradually increased during the study: baseline 3.8 ± 1.9 μg/week, 12 months 5.2 ± 2.4 μg/week; 24 months 6.0 ± 2.9 μg/week (P<.001). Serum PTH levels showed a significant fast decline: baseline 288 ± 152 pg/ml; 6 months 226 ± 184 pg/ml; 12 months 207 ± 120; 24 months 193 ± 119 pg/ml (P<.001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92 ± 50 IU/l; 6 months 85 ± 36 IU/l, 12 months 81 ± 39 IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5-0.6 mg/dl) but still within normal range, whereas patients with baseline calcium>10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar.
Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet.
El hiperparatiroidismo secundario es muy prevalente en pacientes trasplantados renales. Cursa con frecuencia con hipercalcemia y se ha asociado al desarrollo de osteopenia y fracturas óseas. El ...paricalcitol ha mostrado su eficacia en el control del hiperparatiroidismo secundario en la enfermedad renal crónica con y sin diálisis, con una baja incidencia de hipercalcemia. La experiencia con paricalcitol en trasplantados renales es muy escasa. El objetivo de este trabajo fue mostrar el efecto sobre el metabolismo mineralóseo del paricalcitol en trasplantados renales con hiperparatiroidismo secundario.
Estudio retrospectivo multicéntrico con trasplantados renales de más de 18 años de edad y más de 12 meses de evolución postrasplante, con función renal estable, que hayan sido tratados con paricalcitol durante más de 12 meses, con seguimiento clínico hasta los 24 meses de tratamiento.
Se incluyó a 69 pacientes, con 120±92 meses postrasplante, con creatinina inicial de 2,2±0,9mg/dl y FG-MDRD 36±20ml/min/1,73 m2. La dosis de paricalcitol se incrementó progresivamente durante el estudio: basal 3,8±1,9μg/semana, 12 meses 5,2±2,4μg/semana; 24 meses 6,0±2,9μg/semana (p<0,001). Los niveles séricos de PTH descendieron de forma rápida y significativa: basal 288±152 pg/ml; 6 meses 226±184 pg/ml; 12 meses 207±120; 24 meses 193±119 pg/ml (p<0,001). Observamos una reducción sobre PTH basal ≥30% en el 42,4% de los pacientes a los 12 meses y en el 65,2% de los pacientes a los 24 meses. La fosfatasa alcalina descendió también significativamente en los 6 primeros meses para luego estabilizarse: basal 92±50 UI/l; 6 meses 85±36 UI/l, 12 meses 81±39 UI/l (p<0,001). Globalmente no hubo modificaciones en el calcio o fósforo séricos ni en la excreción urinaria de calcio. La reducción de PTH fue más importante en trasplantados con niveles séricos más elevados de partida. Observamos que los pacientes con calcio basal más bajo mostraron un incremento significativo de sus cifras de 0,5-0,6mg/dl en promedio aunque manteniéndose en rango de normalidad, mientras que pacientes con calcio basal>10mg/dl mostraron una reducción progresiva de sus cifras. Quince (21,7%) pacientes seguían tratamiento previo con calcitriol y al cambiarlos a paricalcitol precisaron dosis significativamente mayores que los pacientes que no habían recibido calcitriol. El paricalcitol fue asociado a cinacalcet en 11 pacientes, con reducciones significativas de PTH, con evolución similar al resto de la población y con dosis de paricalcitol también similares.
Paricalcitol es eficaz en el tratamiento del hiperparatiroidismo secundario de trasplantados renales. Globalmente no observamos modificaciones significativas de los niveles de calcio ni de fósforo, ni en su excreción urinaria. Los pacientes en tratamiento previo con calcitriol precisaron dosis mayores de paricalcitol. Cuando el paricalcitol se administra a pacientes tratados con cinacalcet, se observa un descenso significativo de la PTH con dosis de paricalcitol similar a pacientes sin cinacalcet.
Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism.
A retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period.
A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2±0.9mg/dl y GFR-MDRD was 36±20ml/min/1.73m2. Paricalcitol doses were gradually increased during the study: baseline 3.8±1.9μg/week, 12 months 5.2±2.4μg/week; 24 months 6.0±2.9μg/week (P<.001). Serum PTH levels showed a significant fast decline: baseline 288±152 pg/ml; 6 months 226±184 pg/ml; 12 months 207±120; 24 months 193±119 pg/ml (P<.001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92±50 IU/l; 6 months 85±36 IU/l, 12 months 81±39 IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5-0.6mg/dl) but still within normal range, whereas patients with baseline calcium>10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar.
Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet.
Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines ...generate a destructive environment for beta-cells known as insulitis, which results in loss of beta-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve beta-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1beta, IFNgamma, and TNFalpha and/or ghrelin. Several proteins involved in survival pathways (ERK1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on beta-cells in basal conditions, but interestingly it activates cell survival pathways, down-regulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on beta-cells.
Introduction: Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been ...observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism. Material and methods: A retrospective multicentre study in kidney transplant recipients aged >18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period. Results: A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2 ± 0.9 mg/dL and GFR-MDRD was 36 ± 20 mL/min/1.73 m2. Paricalcitol doses were gradually increased during the study: baseline 3.8 ± 1.9 μg/week, 12 months 5.2 ± 2.4 μg/week; 24 months 6.0 ± 2.9 μg/week (P < .001). Serum PTH levels showed a significant fast decline: baseline 288 ± 152 pg/mL; 6 months 226 ± 184 pg/mL; 12 months 207 ± 120; 24 months 193 ± 119 pg/mL (P < .001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months and in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92 ± 50 IU/L; 6 months 85 ± 36 IU/L, 12 months 81 ± 39 IU/L (P < .001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5–0.6 mg/dL) but still within normal range, whereas patients with baseline calcium >10 mg/dL showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar. Conclusions: Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet.
Se comparan dos poblaciones burgalesas medievales con cementerios excavados en roca: Palacios de la Sierra (siglos IX-XIII), núcleo con economía basada principalmente en ganadería y explotación ...maderera en un entorno frío y montañoso, y Santa María de Tejuela (siglos VIII-XI), con economía fundamentalmente agrícola en una planicie y clima más cálido. La hipótesis del estudio es que deberían existir diferencias en su dieta. Se han analizado los isótopos estables de C y N de 101 individuos y la patología máxilo-dentaria de 79. Palacios de la Sierra, muestra una dieta con un elevado consumo de proteínas animales, superior al de Santa María de Tejuela, y menor patología dental en general. Las diferencias son estadísticamente significativas entre ambos sexos en Palacios, donde destaca un elevado consumo de proteínas animales y una menor tasa de patología dental entre las mujeres. Los resultados obtenidos están en consonancia con la hipótesis del estudio.
Los pacientes en ventilación mecánica invasiva (VMI) con COVID-19 tienen una alta mortalidad. Falta información sobre cuáles son los factores asociados a mortalidad en estos pacientes con estancia ...hospitalaria menor de 48horas que refleje la gravedad de la enfermedad.
Identificar las variables asociadas con la mortalidad en los pacientes ingresados en la unidad de cuidados intensivos (UCI), en VMI con neumonía grave por COVID-19.
Estudio prospectivo realizado del 1 de marzo al 30 de julio de 2021, en 9 UCI de la ciudad de Medellín, Colombia. Se incluyeron los pacientes adultos que requirieron VMI al ingreso en la UCI, con estancia hospitalaria menor de 48horas. Se estudiaron las siguientes variables: antecedentes personales, exámenes de laboratorio, complicaciones durante la estancia y el tratamiento médico. Un análisis multivariado fue realizado en un modelo de regresión de Poisson con errores robustos.
El 35,8% de los 148 pacientes incluidos en el estudio fallecieron. Los factores de riesgo relacionados con la mortalidad en el análisis multivariado fueron: mayores de 65 años (RR: 2,15 1,36-3,41), continuar con VMI al día 7 de la estancia (RR: 3,13 1,13-8,69) y antecedente de enfermedad renal crónica (RR: 2,09 1,2-3,64). Los pacientes con un valor de proteína C reactiva mayor de 10mg/dl tuvieron menor mortalidad (RR 0,65 0,44-0,95).
Continuar con VMI al día 7, tener más de 65 años o enfermedad renal crónica fueron los factores de riesgo asociados con mortalidad.
Patients on invasive mechanical ventilation (IMV) with COVID-19 have a high mortality. There is a lack of information on the factors associated with mortality in these patients with a hospital stay of less than 48hours, which reflects the severity of the disease.
To identify the variables associated with mortality in patients admitted to the intensive care unit (ICU) in IMV with severe pneumonia due to COVID-19.
Prospective study conducted from March 1 to July 30, 2021, in nine ICUs in the city of Medellín, Colombia. Adult patients who required IMV upon admission to the ICU, with a hospital stay of less than 48hours, were included. The following variables were studied: personal history, laboratory tests, complications during the stay, and medical treatment. A multivariate analysis was performed in a Poisson regression model with robust errors.
Of the 148 patients admitted to the study, 35.8% died. The risk factors related to mortality in the multivariate analysis were: older than 65 years RR 2.15 (1.36 - 3.41), continuing with IMV on day 7 of stay RR 3.13 (1, 13 – 8.69), and a history of chronic kidney disease RR 2.09 (1.2 - 3.64). Patients with a C-reactive protein value greater than 10mg/dL had lower mortality RR 0.65 (0.44 – 0.95).
Continuing IMV on day 7, being over 65 years of age, or chronic kidney disease were the risk factors associated with mortality.
Cytochrome P450 (CYP) enzymes metabolize endogenous compounds such as steroid hormones, fatty acids, and xenobiotics, including drugs and carcinogens. The skeletal muscle is highly exposed to ...circulating xenobiotics; nevertheless the knowledge on the expression of these enzymes not only in adult skeletal muscle but also in younger individuals has been very little. Therefore, the aim of the present study was to investigate the expression of CYP enzymes in healthy skeletal muscles of children and adolescents. This was investigated in a total of 18 biopsies taken from the quadriceps skeletal muscle of younger patients: 9 boys and 9 girls ( less than or equal to 18 years) by using specific antibodies in immunoblots and by RT-PCR mRNA analysis. The mRNA transcripts for CYP1B1 and CYP2E1 were consistently detected in all samples, but in the immunoblot only was identified CYP1B1 protein in four samples. Regarding CYP1A1, CYP3A4 and CYP3A5 enzymes in skeletal muscle, there were found in some samples in both techniques, although with significant inter-individual variations. Finally CYP2W1 only was detected in one sample belonging to the youngest patient. These data show that a range of CYP enzymes are expressed in the skeletal muscle of children and adolescents, suggesting that the metabolism of several xenobiotic chemicals to which humans are exposed takes place in muscle cells. Moreover, since the potential participation of muscles is a fact in pharmacokinetics of many therapeutic drugs, expression of CYPs in skeletal muscle may play an important role in drug-dependent toxicity.
Purpose
– The purpose of this paper is to develop a research model that examines the effect of information overload and information disorganisation upon customers’ perceived risk and purchase ...intention online in a single integrative model. In addition the paper investigates whether internet experience moderates these relationships.
Design/methodology/approach
– To achieve the paper's objectives an experiment that involved visiting the ten most visited e-commerce web sites in Spain was conducted. Hypotheses were tested by using structural equation modelling on a data set of 1,396 online shopping customers.
Findings
– The results suggest a positive relationship between information overload and customer purchase intention and that internet experience reinforces this positive effect. Moreover the results confirm that the relationship between information disorganisation and customer purchase intention is not significant and that internet experience does not moderate the relationship. The findings also indicate that perceived risk mediates the relationship between information overload and information disorganisation on customer purchase intention.
Originality/value
– This work contributes to the literature by exploring the phenomenon of information overload and information disorganisation upon customers’ perceived risk and purchase intention in the e-commerce environment as well as the moderating effect of internet experience on these relationships in a single integrative model. The main conclusions of this investigation can be valuable to organisations that implement or intend to implement e-commerce.
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