P1422CATHEPSIN-K IS A POWERFUL DIAGNOSTIC BIOMARKER IN PARATHYROIDECTOMIZED DIALYSIS PATIENTS

Abstract Background and Aims Cathepsin-K (Cts-K) is a lysosomal cysteine protease mainly involved in bone remodeling and resorption. Although it is largely released by lung cells, osteoclasts and macrophages, increasing current evidence suggests that the parathyroids may somewhat regulate Cts-K balance. We therefore analyzed Cts-K in a cohort of 85 chronic HD patients (mean age 67+/-12, median dialysis vintage 3.2 yrs), also including some individuals who were previously parathyroidectomized. Method Cts-K serum levels were measured before a mid-week dialysis session together with standard biochemical parameters. Twenty-six healthy subjects matched for age and gender served as controls. Patients were further stratified according to whether they were parathyroidectomized or not. Results Cts-K levels were statistically higher in HD patients than in controls (median 340, IQR 170-835 vs. 190 IQR 20-120 pg/mL, p<0.0001) and significantly associated with ALP (r=0.50, p<0.001), CRP (r=0.46,p<0.001) and PTH (r=0.24,p=0.02). Patients with previous parathyroidectomy (n=8) had significantly lower levels of Cts-K (942.3 vs 46.2 pg/mL, p<0.0001). At ROC analyses, Cts-K showed an excellent diagnostic profile in distinguishing parathyroidectomized patients (AUC 0.977, best Cts-K cutoff< 100 pg/mL; sens. 100%, spec. 93%; Figure 1). Of note, although slightly inferior, the AUC of Cts-K was not statistically different to that of PTH (p=0.11 for comparison of ROC curves). Conclusion Cathepsin-K may represent a potential candidate biomarker for diagnosing and managing MBD complications, particularly those related to parathyroid dysfunction. Its exact biological role in these conditions deserves further examination.

Download Full-text

Creatine-Kinase- and Exercise-Related Muscle Damage Implications for Muscle Performance and Recovery

Journal of Nutrition and Metabolism ◽

10.1155/2012/960363 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 180

Author(s):

Marianne F. Baird ◽

Scott M. Graham ◽

Julien S. Baker ◽

Gordon F. Bickerstaff

Keyword(s):

Creatine Kinase ◽

Muscle Damage ◽

Serum Levels ◽

Muscle Performance ◽

Health Concern ◽

Current Evidence ◽

Scientific Integrity ◽

Cerebral Diseases ◽

And Gender ◽

The Impact

The appearance of creatine kinase (CK) in blood has been generally considered to be an indirect marker of muscle damage, particularly for diagnosis of medical conditions such as myocardial infarction, muscular dystrophy, and cerebral diseases. However, there is controversy in the literature concerning its validity in reflecting muscle damage as a consequence of level and intensity of physical exercise. Nonmodifiable factors, for example, ethnicity, age, and gender, can also affect enzyme tissue activity and subsequent CK serum levels. The extent of effect suggests that acceptable upper limits of normal CK levels may need to be reset to recognise the impact of these factors. There is a need for standardisation of protocols and stronger guidelines which would facilitate greater scientific integrity. The purpose of this paper is to examine current evidence and opinion relating to the release of CK from skeletal muscle in response to physical activity and examine if elevated concentrations are a health concern.

Download Full-text

P1417ALTERED CATHEPSIN-K LEVELS REFLECT SEVERITY OF MINERAL BONE DISEASE AND INFLAMMATION IN CHRONIC HEMODIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1417 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Giuseppe Coppolino ◽

Marta Greco ◽

Giuseppe Leonardi ◽

Michele Provenzano ◽

Omar Tripolino ◽

...

Keyword(s):

Bone Disease ◽

Calcium Concentration ◽

Cathepsin K ◽

Hemodialysis Patients ◽

Chronic Hemodialysis ◽

Future Research ◽

Dialysis Session ◽

Dialysis Patients ◽

Dialysis Vintage ◽

Dialysate Calcium

Abstract Background and Aims Mineral bone disease (MBD) and chronic inflammation are key triggers of the exceeding cardiovascular risk that characterizes dialysis patients. Cathepsin-K (Cts-K) is a lysosomal cysteine protease involved in bone remodeling and resorption, whose expression is promoted particularly by inflammation and whose involvement in bone and cardiovascular disorders has previously been demonstrated. We set out to undertake an exploratory, observational study to assess the possible clinical significance of Cts-K in dialysis patients. Method Eighty-five chronic HD patients (mean age 67±12, median dialysis vintage 3.2 yrs) with stable dry weight were studied. Cts-K was measured in peripheral blood samples before a mid-week dialysis session together with standard biochemical parameters. Twenty-six healthy subjects, matched with HD patients for age and gender, served as controls. Results Cts-K was statistically higher in HD patients than in controls (median 340, IQR 170-835 vs. 190 IQR 20-120 pg/mL, p<0.0001). At univariate analyses, Cts-K levels were significantly associated with ALP (r=0.50, p<0.001), CRP (r=0.46, p<0.001), PTH (r=0.24,p=0.02), presence of diabetes (r=0.28,p<0.001),peripheral vasculopathy (r=0.20, p=0.05) and dialysate calcium concentration (r=-0.28,p<0.001). In a multivariate model including all univariate predictors (R2=61%, p<0.001) only ALP (β=0.70,p<0.001), CRP (β=0.49,p<0.001) and dialysate calcium concentration (β -0.40,p=0.04) remained significantly associated with Cts-K levels. Interestingly, Cts-K levels were significantly higher among individuals who were under active calcimimetic therapy (n=28; p<0.001) but significantly lower among those who previously underwent parathyroidectomy (n=8; p<0.001) (Figure 1). Conclusion Cathepsin-K is a biomarker at the crossroads of bone and inflammatory disorders in chronic hemodialysis patients. Future research is needed to clarify the exact pathophysiological role of this protein and to test its potential usefulness as a marker for managing MBD therapy and complications.

Download Full-text

Contact precautions for colonisation with multidrug-resistant organisms and haemodialysis patient quality of life and mood: a pilot case-control study

Renal Society of Australasia Journal ◽

10.33235/rsaj.15.1.19-25 ◽

2019 ◽

pp. 19-25 ◽

Cited By ~ 1

Author(s):

Rathika Krishnasamy

Keyword(s):

Quality Of Life ◽

Qualitative Interviews ◽

Social Function ◽

Multidrug Resistant ◽

Contact Precautions ◽

Dialysis Vintage ◽

Multidrug Resistant Organisms ◽

And Gender ◽

The Impact

Background: The rate of multidrug-resistant organisms (MDRO) colonisation in dialysis populations has increased over time. This study aimed to assess the effect of contact precautions and isolation on quality of life and mood for haemodialysis (HD) patients colonised with MDRO. Methods: Patients undergoing facility HD completed the Kidney Disease Quality of Life (KDQOL–SFTM), Beck Depression Inventory (BDI) and Personal Wellbeing-Index Adult (PWI-A). Patients colonised with MDRO were case-matched by age and gender with patients not colonised. Results: A total of 16 MDRO-colonised patients were matched with 16 controls. Groups were well matched for demographics and co-morbidities, other than a trend for older dialysis vintage in the MDRO group [7.2 years (interquartile range 4.6–10.0) compared to 3.2 (1.4–7.6) years, p=0.05]. Comparing MDRO-positive with negative patients, physical (30.5±10.7 vs. 34.6±7.3; p=0.2) and mental (46.5±11.2 vs. 48.5±12.5; p = 0.6) composite scores were not different between groups. The MDRO group reported poorer sleep quality (p=0.01) and sleep patterns (p=0.05), and lower social function (p=0.02). BDI scores were similar (MDRO-positive 10(3.5–21.0) vs. MDRO-negative 12(6.5–16.0), p=0.6). PWI-A scores were also similar in both groups; however, MDRO patients reported lower scores for “feeling safe”, p=0.03. Conclusion: While overall scores of quality of life and depression were similar between groups, the MDRO group reported poorer outcomes in sleep and social function. A larger cohort and qualitative interviews may give more detail of the impact of contact precautions and isolation on HD patients. The necessity for contact precautions for different MDRO needs consideration.

Download Full-text

Vitamin D Deficiency as a Risk Factor for Myocardial Ischemia

Medicina ◽

10.3390/medicina57080774 ◽

2021 ◽

Vol 57 (8) ◽

pp. 774

Author(s):

Christina Batsi ◽

Evangelia Gkika ◽

Loukas Astrakas ◽

Athanassios Papadopoulos ◽

Ioannis Iakovou ◽

...

Keyword(s):

Vitamin D ◽

Risk Factor ◽

Myocardial Ischemia ◽

Single Photon ◽

Statistical Significance ◽

Photon Emission ◽

Serum Levels ◽

Emission Computed Tomography ◽

And Gender ◽

D Values

Background and Objectives: Vitamin D (Vit D) deficiency has been implicated in various conditions, including cardiovascular disease. The purpose of this retrospective study was to investigate the incidence of patients with myocardial ischemia in relation to their serum levels of vitamin D. Materials and Methods: A 64-month search (January 2016 to April 2021) in our database of the Nuclear Medicine Laboratory revealed 113 patients who had both myocardial perfusion imaging with single photon emission computed tomography (MPI SPECT) and Vit D measurements. MPI SPECT obtained myocardial images during both stress (summed stress score, SSS) and rest (summed rest score, SRS). Abnormal MPI SPECT was when the SSS was ≥4. Vit D was determined by radioimmunoassay (RIA). Patients with Vit D values <10 ng/mL, 10–29 ng/mL and ≥30 ng/mL were defined as having a deficiency, insufficiency and sufficiency, respectively. Results: Among patients, 46/113 (40.7%) were male and 67/113 (59.3%) were female. Abnormal MPI was found in 58/113 (51.3%) patients. Vit D deficiency was noted in 20/113 (17.7%) patients, insufficiency in 86/113 (76.1%) patients, and normal Vit D was noted in only 7/113 (6.2%) patients. Sixteen of the 20 patients (80%) with Vit D deficiency, and 38/86 (44.2%) with insufficiency had an abnormal MPI SPECT. In contrast, only 1/7 (14.3%) patients with sufficient Vit D levels had an abnormal MPI SPECT. The Mann-Whitney U-test showed that ischemia reduced the values of Vit D. Correlation analysis showed a negative association of Vit D levels with SSS (rho = −0.232, p = 0.014) and SRS (rho = −0.250, p = 0.008). Further evaluation with a Vit D cut off 20 ng/mL retrieved no statistical significance. Finally, Vit D and gender were independently associated with myocardial ischemia. Conclusions: Low Vit D levels may represent a risk factor for myocardial ischemia.

Download Full-text

Age- and Gender-Related Differences in LDL-Cholesterol Management in Outpatients with Type 2 Diabetes Mellitus

International Journal of Endocrinology ◽

10.1155/2015/957105 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Giuseppina Russo ◽

Basilio Pintaudi ◽

Carlo Giorda ◽

Giuseppe Lucisano ◽

Antonio Nicolucci ◽

...

Keyword(s):

Type 2 Diabetes ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Serum Levels ◽

Diabetes Duration ◽

Lipid Lowering ◽

Age And Gender ◽

Chd Risk ◽

And Gender

Background. Dyslipidemia contribute to the excess of coronary heart disease (CHD) risk observed in women with type 2 diabetes (T2DM). Low density lipoprotein-cholesterol (LDL-C) is the major target for CHD prevention, and T2DM women seem to reach LDL-C targets less frequently than men.Aim. To explore age- and gender-related differences in LDL-C management in a large sample of outpatients with T2DM.Results. Overall, 415.294 patients (45.3% women) from 236 diabetes centers in Italy were included. Women were older and more obese, with longer diabetes duration, higher total-cholesterol, LDL-C, and HDL-C serum levels compared to men (P<0.0001). Lipid profile was monitored in ~75% of subjects, women being monitored less frequently than men, irrespective of age. More women did not reach the LDL-C target as compared to men, particularly in the subgroup treated with lipid-lowering medications. The between-genders gap in reaching LDL-C targets increased with age and diabetes duration, favouring men in all groups.Conclusions. LDL-C management is worst in women with T2DM, who are monitored and reach targets less frequently than T2DM men. Similarly to men, they do not receive medications despite high LDL-C. These gender discrepancies increase with age and diabetes duration, exposing older women to higher CHD risk.

Download Full-text

Polychlorinated biphenyls and risk of hepatocellular carcinoma in the population living in a highly polluted area in Italy

Scientific Reports ◽

10.1038/s41598-021-82657-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Francesco Donato ◽

Marco Moneda ◽

Nazario Portolani ◽

Angelo Rossini ◽

Sarah Molfino ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Polychlorinated Biphenyls ◽

Serum Levels ◽

Polluted Area ◽

Sufficient Evidence ◽

Pcb Congeners ◽

Non Hodgkin Lymphoma ◽

And Gender ◽

Few Data ◽

Incident Cases

AbstractPolychlorinated biphenyls (PCBs) are human carcinogens, based on sufficient evidence for melanoma and limited evidence for non-Hodgkin lymphoma and breast cancer. Few data are available for liver cancer, although PCBs cause it in rats and determined liver damage in poisoned people. We investigated the association between PCB serum levels and hepatocellular carcinoma (HCC) with a case–control study in a PCB-polluted area in North Italy. We enrolled prospectively 102 HCC incident cases and 102 age and gender-matched hospital controls. Serum concentrations of 33 PCB congeners were determined by a gas chromatograph coupled to mass spectrometry. Of 102 HCC cases, 62 who had lost < 3 kg of body weight in past 3 years were included in the analysis (67.7% males, mean age 68 years). The odds ratio (OR) for HCC for 3rd compared to 1st tertile of PCB distribution was 1.76 (95% confidence interval 0.62–5.03) for total PCB, adjusting for socio-demographic variables and risk factors for HCC by logistic regression. For most PCB congeners, ORs > 1.5 or 2 were found, although the 95% CIs included the null value for almost all of them. This preliminary study suggests that PCBs might play a role in HCC development.

Download Full-text

ENDOCRINE STUDIES AND SUCCESSFUL TREATMENT IN A PATIENT WITH TRUE HERMAPHRODITISM

Acta Endocrinologica ◽

10.1530/acta.0.0910184 ◽

1979 ◽

Vol 91 (1) ◽

pp. 184-192

Author(s):

Evangelina Valdés ◽

Carlos Fernández del Castillo ◽

Raul Gutiérrez ◽

Fernando Larrea ◽

Martha Medina ◽

...

Keyword(s):

Chromosome Complement ◽

Reproductive Function ◽

External Genitalia ◽

Serum Testosterone ◽

Serum Levels ◽

Normal Children ◽

Serum Lh ◽

Genital Ambiguity ◽

And Gender ◽

Lh Rh

ABSTRACT A 12-year old, 46 XX true hermaphrodite born with genital ambiguity was studied and successfully treated. The serum LH and FSH profile resembled that of a pubertal normal individual, and LH-RH administration induced a normal LH response. Baseline testosterone serum levels were within the range for normal children. Exogenous HCG stimulation induced a significant serum testosterone increase up to values similar to those observed in normal post-pubertal males. Surgical examination disclosed the presence of bilateral ovotestis, normal Mullerian derivatives, epididymis, and vas deferens. A complete ovotestis with testicular predominance and the testicular portion of the contralateral ovotestis as well as the Wolffian derivatives, were removed. A further HCG stimulation 3 months after surgery, failed to induce serum testosterone increase. Spontaneous menarche was observed 6 months after surgery and ovulation was well documented. At present the patient has several characteristics of female sex including those of chromosome complement, gonad, internal and external genitalia, hormone levels and gender identity, thus demonstrating that treatment was successful and that reproductive function could be obtained. The finding of spontaneous ovulation following removal of the testicular portion suggests normal cyclic gonadotrophic release implying a difference between animal models and man in regard to hypothalamic virilization.

Download Full-text

Low Serum Alpha-1 Antitrypsin (AAT) in Family Members of Individuals with Autism Correlates with PiMZ Genotype

Biomarker Insights ◽

10.4137/bmi.s1115 ◽

2009 ◽

Vol 4 ◽

pp. BMI.S1115 ◽

Cited By ~ 6

Author(s):

Anthony J. Russo ◽

Lauren Neville ◽

Christine Wroge

Keyword(s):

Gastrointestinal Disease ◽

Family Members ◽

Serum Levels ◽

Normal Serum ◽

Autistic Children ◽

Respiratory Problems ◽

Low Levels ◽

Alpha 1 Antitrypsin ◽

And Gender ◽

Low Serum

Aim Deficiency of Alpha-1-antitrypsin (AAT) can be a genetic condition that increases the risk of developing liver, lung and possibly gastrointestinal disease. Since many autistic children also have gastrointestinal disorders, this study was designed to measure serum concentration of AAT and establish AAT genotypes in autistic children, age and gender matched non-autistic siblings, parents and controls. Subjects and Methods We used an indirect ELISA with monoclonal IgG to AAT to measure AAT serum concentrations in 71 members from 16 families of individuals with autism and 18 controls (no family history of autism). We used a duplex polymerase chain reaction to detect M, S and Z alleles for alpha-1 antitrypsin expression in 52 members of 12 of the above families. Results A significantly high number of autistic family members had lower than normal serum levels of AAT when compared to controls. Autistic children with regressive onset had significantly lower levels of AAT compared to controls, and a significant number of autistic children with low serum AAT also had hyperbilirubinemia, gastrointestinal disease and respiratory problems. We also found that a significantly high number of these individuals had the PiMZ genotype and correspondingly low levels of serum alpha-1 antitrypsin. Discussion Knowing that low levels of alpha-1 antitrypsin may be inherited, and that low levels of AAT may be associated with GI disease in autistic children, genotyping autistic children may help identify individuals susceptible to developing digestive problems.

Download Full-text

Gender Differences in Diabetic Kidney Disease: Focus on Hormonal, Genetic and Clinical Factors

International Journal of Molecular Sciences ◽

10.3390/ijms22115808 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5808

Author(s):

Annalisa Giandalia ◽

Alfio Edoardo Giuffrida ◽

Guido Gembillo ◽

Domenico Cucinotta ◽

Giovanni Squadrito ◽

...

Keyword(s):

Gender Differences ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Clinical Manifestations ◽

Current Evidence ◽

Sex And Gender ◽

Clinical Factors ◽

Diabetic Kidney ◽

And Gender ◽

The Impact

Diabetic kidney disease (DKD) is one of the most serious complications of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Current guidelines recommend a personalized approach in order to reduce the burden of DM and its complications. Recognizing sex and gender- differences in medicine is considered one of the first steps toward personalized medicine, but the gender issue in DM has been scarcely explored so far. Gender differences have been reported in the incidence and the prevalence of DKD, in its phenotypes and clinical manifestations, as well as in several risk factors, with a different impact in the two genders. Hormonal factors, especially estrogen loss, play a significant role in explaining these differences. Additionally, the impact of sex chromosomes as well as the influence of gene–sex interactions with several susceptibility genes for DKD have been investigated. In spite of the increasing evidence that sex and gender should be included in the evaluation of DKD, several open issues remain uncovered, including the potentially different effects of newly recommended drugs, such as SGLT2i and GLP1Ras. This narrative review explored current evidence on sex/gender differences in DKD, taking into account hormonal, genetic and clinical factors.

Download Full-text

Hair Magnesium content and its relation to Serum Magnesium level in children with Idiopathic Epilepsy

QJM ◽

10.1093/qjmed/hcab113.005 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Hamed Mahmoud Shatla ◽

Mariam Fathy Abdel Maksoud ◽

Raghda Mohamed Hesham Zaitoun ◽

Alaa Rabie Abdel Baset Mahmoud

Keyword(s):

Serum Magnesium ◽

Serum Levels ◽

Magnesium Content ◽

Magnesium Level ◽

Idiopathic Epilepsy ◽

Age And Gender ◽

Control Subjects ◽

Significant Difference ◽

And Gender ◽

Patients With Epilepsy

Abstract Objective To measure the level of hair Mg, as well as its level in serum, in patients with epilepsy and compare them to the levels found in non-epileptic age and gender matched children, and to explore any potential correlation between either serum or hair level of magnesium and seizure characteristics in children with idiopathic epilepsy. Methods An observational cross-sectional study including 50 children with idiopathic epilepsy and 100 non-epileptic age and gender matched control subjects. Cases were subjected to full history taking, examination and measurements of serum and hair levels of magnesium, control subjects only had their serum and hair level of magnesium measured as for the cases. Results The mean serum magnesium was 29.11 ± 13.42 ug/ml for cases and 27.67 ± 7.24 ug/ml for controls and the median hair level of magnesium was 42.22 ug/g with IQR of 25.9 - 56.82 for cases and 38.6 ug/g with IQR of 25.21 - 61.25 for controls. No statistically significant difference was observed between both groups as regards either serum or hair magnesium levels. No statistically significant correlation was observed between either hair or serum levels of magnesium and seizure characteristics though the correlations were nearing statistical significance for the hair magnesium content. Conclusion Hair magnesium level may be better correlated to seizure characteristics and control than serum levels in patients with epilepsy.

Download Full-text