Disturbances Of Calcium Metabolism Research Articles

Effect of stapes demineralisation on the development of cochlear otosclerosis.

The involvement of the inner ear in otosclerosis may lead to the development of cochlear otosclerosis. The aim of this study was to analyse changes in the chemical composition and microstructure of the stapes in the course of otosclerosis compared to healthy stapes. This analysis included 31 patients with otosclerosis and 9 patients without otosclerosis. Microanalytical and diffraction techniques were used to assess the elemental distribution and orientation topography of the stapes. The concentration of Ca2+ in the study group was significantly lower in the area of the anterior crus of the stapes than in the posterior crus. A reduction in the Ca2+/P3+ ratio in the anterior crus was associated with deteriorated bone conduction and tinnitus. Degradation of the stapes microstructure in the area of otosclerotic lesions was observed with scanning electron microscopy. Bone remodelling is most significant at the closest location to typical otosclerotic lesions with hydroxyapatite porosity and scale-like bone formation according to scanning electron microscopy. There is a relationship between the disturbance of calcium metabolism and the development of clinical symptoms of cochlear otosclerosis.

Explorative research on glucolipid metabolism and levels of adipokines in pseudohypoparathyroidism type 1 patients

BackgroundPseudohypoparathyroidism type 1 (PHP1) is a rare disease featuring hypocalcemia and elevated PTH level. Though disturbed calcium and phosphorus metabolism under PTH resistant have been widely studied, glucolipid metabolism abnormalities observed in PHP1 patients have received little attention. The aim of this research is to explore the glucolipid metabolism features in a rather large cohort of PHP1 patient. In the current study, PHP1 patients and primary hyperparathyroidism patients as well as normal control were recruited for the investigation. Glucolipid metabolic indices as well as the level of four adipokines were examined.ResultsA total of 49 PHP1 patients, 64 PHPT patients and 30 healthy volunteers were enrolled. A trend of higher HOMA-β index was found in PHP1 patients than normal controls (median 97.08% vs 68.19%, p = 0.060). Both the PHP1 and PHPT group presented with significantly lower TNFα level compared to normal controls (average 10.74 pg/ml and 12.53 pg/ml vs 15.47 pg/ml, p = 0.002 and 0.041, respectively). FGF21 level was significantly higher in PHPT group than in PHP1 group (median 255.74 pg/ml vs 167.46 pg/ml, p = 0.019). No significant difference in glucolipid metabolic indices and adipokines was found between PHP1A or PHP1B patients and normal controls, while overweight/obese PHP1 patients tended to have higher leptin than normal-BMI cases (p = 0.055). Multiple linear regression analysis showed BMI rather than PTH or HOMA-IR to be an independent variable of leptin in PHP1.ConclusionMetabolic stress given upon especially overweight PHP1 patients may resulted in possible β-cell compensation. Elevated TNFα may be related with hyper-PTH level regardless of calcium level.

Abnormal grey matter structural changes in patients with end-stage kidney disease and mild cognitive impairment: correlations with clinical features

End-stage kidney disease and mild cognitive impairment (ESKD-MCI) affect the quality of life and long-term treatment outcomes of patients affected by these diseases. Clarifying the morphological changes from brain injuries in ESKD-MCI and their relationship with clinical features is helpful for the early identification and intervention of MCI before it progresses to irreversible dementia. This study gathered data from 23 patients with ESKD-MCI, 24 patients with ESKD and non-cognitive impairment (NCI), and 27 health controls (HCs). Structural magnetic resonance studies, cognitive assessments, and general clinical data were collected from all participants. Voxel-based morphometry analysis was performed to compare grey matter (GM) volume differences between the groups. The patients’ GM maps and clinical features were subjected to univariate regression to check for possible correlations. Patients with ESKD-MCI displayed significantly more impairments in multiple cognitive domains, including global cognition, visuospatial and executive function, and memory, compared to patients with ESKD-NCI. Using a more liberal threshold (P < 0.001, uncorrected), we found that compared to patients with ESKD-NCI, patients with ESKD-MCI exhibited clusters of regions with lower GM volumes, including the right hippocampus (HIP), parahippocampal gyrus (PHG), Rolandic operculum, and supramarginal gyrus. The volumes of the right HIP and PHG were negatively correlated with serum calcium levels. ESKD-MCI was associated with a subtle volume reduction of GM in several brain areas known to be involved in memory, language, and auditory information processing. We speculate that these slight morphometric impairments may be associated with disturbed calcium metabolism.

The risk of osteoporosis is not increased after cholecystectomy. A nationwide cohort study

Cholecystectomy alters bile flow and quality which might compromise the absorption of vitamin D and vitamin K which are important for bone health. We aimed to assess the risk of osteoporosis after cholecystectomy. MethodsWe performed a nationwide, register-based, cohort study using individual-level data from the Danish Health Registers. Individuals who had cholecystectomy performed between 1995 and 2017 were included as were five sex- and aged-matched controls for each case. We assessed fractures, ICD diagnosis of osteoporosis and osteoporosis treatments. We defined a composite endpoint for osteoporosis consisting of 1) hip or spine fractures, 2) ICD diagnosis of osteoporosis or 3) osteoporosis treatments. ResultsWe included 149.968 cases and 727.456 controls that were followed for a median of 9 years (inter-quartile range 4–15 years). In the cholecystectomy cohort, 6.4 % reached the composite endpoint compared to 6.6 % in the reference population (HR 0.98 (0.96–1.03)). In age-stratified analyses, minor risk increases were observed in the cholecystectomy cohort compared to the reference population in the composite endpoint for osteoporosis (age group ≤30 years, 0.8 % vs. 0.6 %, HR 1.42 (1.19–1.71)), fractures rates (≤30 years incidence rate ratio (IRR) 1.38 (1.32–1.43), age group 31–50 years IRR 1.10 (1.08–1.43)) and ICD osteoporosis diagnosis (≤30 years, 0.3 % vs. 0.2 % HR 1.40 (1.04–1.87)). ConclusionThe risk of osteoporosis was similar in patients with prior cholecystectomy and controls. In younger subgroups, the risk of osteoporosis and fractures was slightly increased but absolute risks were low. These findings do not support that cholecystectomy leads to any major calcium-metabolic disturbances.

Proteomic analysis of sialoliths from calcified, lipid and mixed groups as a source of potential biomarkers of deposit formation in the salivary glands

Salivary stones, also known as sialoliths, are formed in a pathological situation in the salivary glands. So far, neither the mechanism of their formation nor the factors predisposing to their formation are known despite several hypotheses. While they do not directly threaten human life, they significantly deteriorate the patient’s quality of life. Although this is not a typical research material, attempts are made to apply various analytical tools to characterise sialoliths and search for the biomarkers in their proteomes. In this work, we used mass spectrometry and SWATH-MS qualitative and quantitative analysis to investigate the composition and select proteins that may contribute to solid deposits in the salivary glands. Twenty sialoliths, previously characterized spectroscopically and divided into the following groups: calcified (CAL), lipid (LIP) and mixed (MIX), were used for the study. Proteins unique for each of the groups were found, including: for the CAL group among them, e.g. proteins from the S100 group (S100 A8/A12 and P), mucin 7 (MUC7), keratins (KRT1/2/4/5/13), elastase (ELANE) or stomatin (STOM); proteins for the LIP group—transthyretin (TTR), lactotransferrin (LTF), matrix Gla protein (MPG), submandibular gland androgen-regulated protein 3 (SMR3A); mixed stones had the fewest unique proteins. Bacterial proteins present in sialoliths have also been identified. The analysis of the results indicates the possible role of bacterial infections, disturbances in calcium metabolism and neutrophil extracellular traps (NETs) in the formation of sialoliths.

Subcellular compartmentalization of STIM1 for the distinction of Darier disease from Hailey-Hailey disease.

Darier disease (DD) and Hailey-Hailey disease (HHD) are rare disorders caused by mutations in the ATPase, Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 2 (ATP2A2) and ATPase Ca2+ Transporting Type 2C, Member 1 (ATP2C1) gene, respectively, which lead to a disturbance of calcium metabolism in keratinocytes. Clinically, this is reflected by an impairment of keratinization. Histologically, acantholysis with variable degrees of dyskeratosis and parakeratosis is observed. Both diseases can usually be differentiated clinically, histopathologically and genetically. However, their routine distinction might be challenging since some patients do not harbor ATP2A2 or ATP2C1 mutations. To solve this diagnostic challenge, we studied the differential expression of two proteins of store-operated calcium entry (SOCE), stromal interaction molecule1 (STIM1) and calcium release-activated calcium modulator1 (ORAI1), by immunohistochemistry. Five individuals with ambiguous diagnostic findings and eight controls with an unambiguous diagnosis were studied clinically, histologically, genetically, and by immunohistochemistry for STIM1 and ORAI1. DD patients consistently showed a cytoplasmic STIM1 expression while patients with HHD revealed a membrane-associated staining pattern. In contrast, ORAI1 did not show a differential expression pattern. Our data suggest subcellular compartmentalization of STIM1 as novel biomarker for the distinction of the two disorders.

MO817: New Scenarios in Use of Calcimimetics: Could Etelcalcetide Improve Anaemia?

Abstract BACKGROUND AND AIMS Alterations of mineral metabolism in patients with chronic renal failure (MBD-CKD) are frequently found and appear in the earliest stages of the disease. If not accurately diagnosed and treated, they could lead to serious clinical complications. With the same safety and better tolerability compared with cinacalcet, etelcalcetide demonstrated greater efficacy in the control of parathyroid hormone (iPTH) with an improvement in patients' compliance. Several reports in the literature document the effect of elevated levels of iPTH on anaemia. In vitro experiments showed that elevated concentrations of PTH (comparable to those found in the blood of uraemic patients with secondary hyperparathyroidism) exert a significant inhibition on erythroid progenitors, decreasing the number of erythropoietin receptors on erythroid progenitors and making these cells insensitive to erythropoietin. High levels of iPTH could have, furthermore, a haemolytic effect on the peripheral RBCs causing disturbed calcium metabolism, increased cytosolic calcium and enhanced osmotic fragility of the cells. Aim of this study was to verify in a dialysis cohort if etelcalcetide could not only improve iPTH levels but also haemoglobin levels with a reduction in weekly doses of erythropoiesis-stimulating agents (ESA). METHOD We analysed data from 130 haemodialysis adult patients over 2 years from three different centres. A total of 24 patients treated with etelcalcetide (Image 1) were enrolled and followed at different time points (1–3–6–12–24 months). Patients were on stable doses of ferric carboxymaltose, active vitamin D analogues, phosphorus binders, supplement of oral calcium and calcium concentration in dialysate (1.25–1.50 mmol/L). RESULTS Data analysed after 24 months of treatment with etelcalcetide (Image 2) demonstrated not only a drastic improvement in iPTH values (772.53 ± 452.6 pg/mL versus 308.7 ± 207 pg/mL–60.05%) but also a statistically significant improvement of haemoglobin values ( 10.35 ± 1.45 g/dL versus 11.57 ± 0.97 g/dL;  P &amp;lt; .05) in addition to a reduction in the weekly ESAs units required (193.39 ± 148 UI/kg/week versus 142.71 ± 118 UI/kg/week; P &amp;lt; .05). This effect was achieved by maintaining constant ferritin and TSAT levels and without substantial changes in iron carboxymaltose therapy. No side effects were recorded for the entire duration of the treatment. CONCLUSIONS Considering the well-known direct and indirect inhibition of parathyroid hormone on erythropoiesis, reduction of iPTH levels achieved with etelcalcetide could improve haemoglobin levels and reduce required weekly ESA units, with obvious clinical and economic advantages. Further studies, on large populations and over longer periods of time, are required.

Updates for the diagnosis and management of cardiac amyloidosis.

A substantial increase in the interest in transthyretin cardiac amyloidosis (ATTR-CA) is a result of the constantly growing number of patients, the use of clear diagnostic protocols and the availability of the first selective drug for these patients. This has also raised the awareness of the disease among physicians of all specialties. The topic is particularly relevant to cardiologists, who use non-invasive multimodal imaging in their daily practice. The differential diagnosis of the causes of myocardial hypertrophy includes arterial hypertension, hypertrophic cardiomyopathy, aortic stenosis (AS), athletic heart syndrome, Fabry disease, and cardiac amyloidosis (CA). It turns out that in patients with myocardial hypertrophy >15 mm, amyloidosis is the most common cause of left ventricular (LV) hypertrophy. In parallel, CA is one of the most common infiltrative diseases leading to a clinical picture that may mimic heart failure with preserved ejection fraction (HFpEF). The accumulation of amyloid in the extracellular space impairs the diastolic function of the myocardium, which is observed as the restrictive cardiomyopathy phenotype. In advanced cases, the LV systolic function is also impaired. Moreover, protein deposits contribute to the disturbances of calcium metabolism and cell metabolism as well as to cardiotoxicity, leading to edema and damage to cardiomyocytes.

Salivary Alpha-Amylase and Calcium levels Evaluation as a Biomarker in Stress Patients Undergoing Surgical Wisdom Tooth Extraction

The salivary enzyme alpha-amylase has been proposed as a biomarker for stress-induced activity of the sympathetic nervous system. In the growing field of amylase research, recent studies have underscored the usefulness of salivary alpha-amylase in this regard. Calcium is the major component of bones and teeth, and it is not surprising that disturbances in calcium metabolism have been implicated in most of the major chronic diseases, including renal disease, osteoporosis; and periodontal tissues.Twenty healthy Iraqi male undergo wisdom tooth extraction from undergraduates dental students were considered in this study with age mean of 22 years old, 2 ml samples of stimulated saliva were collected prior ten mints of surgical wisdom tooth removal, and recollected after one week fromsurgery from these students, the samples were analyzed to assess changes in ∝-amylase and calcium ion concentration under controlled conditions. The collected data predicted elevation of amylase level from ((7652.965 ±34.0410) to (7674.710 ± 68.8958) IU/L) with a significant change. And also increase in the calcium ion concentration level from (0.1465 ± 0.048) to reach level (0.1975± 0.100) mmol/L. Positive correlation were recorded between alpha amylase and calcium concentration when plotted the correlations values of stress and no stress individual's. In a conclusion. Acute stresscaused by wisdom tooth removal will elevate level of amylase in saliva significantly, howeverSignificant increasing in calcium concentration was observed in the stimulated saliva in comparison with the non-stimulated saliva with significant mean changes. However, our result predicted elevated levels of calcium concentration of the stimulated saliva than the non-stimulated (after extraction).

The value of the analysis of the urinary stones for studying the features of urolithiasis pathogenesis

Introduction. Urolithiasis is a multifactorial recurrent disease, unevenly spread throughout the world and characterizedby the formation of urinary stones of various chemical compositions, depending on pathogenesis, etiological, and epidemiological risk factors. Understanding the composition of chemicals and their prevailing ratios can help make decisions about treatment tactics, preventive measures to reduce the risk of recurrence and the prevalence of urolithiasis.Purpose of the study. To assess the distribution of chemical components in urinary stones along with an analysis of their population significance.Materials and methods. The urinary stones were obtained from 2854 patients with urolithiasis. The composition of urinary stones was analyzed by using an infrared spectroscopy method.Results. The predominance of oxalate stones was determined in multicomponent kidney stones (83,7%) and the prevalence of urate stones (54,2%) was revealed in monocomponent kidney stones. Urinary stones with a predominance of oxalates contained significantly fewer impurities (12.4%) than urinary stones with a predominance of urates, phosphates and carbonates with an average amount of impurities &gt;24.0%.Conclusion. The analysis of urinary stones distribution based on pathogenic factors showed that the calcium metabolism disturbances prevail in the population of the Russian Federation (88.0%).

Проблема остеопороза в общеврачебной практике: распространенность, факторы риска, генетические предикторы. Роль хронического панкреатита и гипертонической болезни в формирование вторичного остеопороза

The combination of socially significant common chronic non-infectious diseases of internal organs, the interaction of their pathogenetic links quite often leads to the development of complications that affect the course of the main nosology. Among these tandems, chronic pancreatitis and hypertension are considered — calcium-dependent diseases, the comorbidity of which can affect the disturbances in calcium metabolism, thereby contributing to the formation of osteopenic conditions. A number of researchers have established that the development of diseases such as chronic pancreatitis and hypertension, and their complications (namely, osteoporosis) can be the result of the presence of candidate genes, the unfavorable polymorphism of which can provoke changes in the pathogenetic directions of the diseases course.

Uremic Toxins, Oxidative Stress, Atherosclerosis in Chronic Kidney Disease, and Kidney Transplantation.

Patients with chronic kidney disease (CKD) are at a high risk for cardiovascular disease (CVD), and approximately half of all deaths among patients with CKD are a direct result of CVD. The premature cardiovascular disease extends from mild to moderate CKD stages, and the severity of CVD and the risk of death increase with a decline in kidney function. Successful kidney transplantation significantly decreases the risk of death relative to long-term dialysis treatment; nevertheless, the prevalence of CVD remains high and is responsible for approximately 20-35% of mortality in renal transplant recipients. The prevalence of traditional and nontraditional risk factors for CVD is higher in patients with CKD and transplant recipients compared with the general population; however, it can only partly explain the highly increased cardiovascular burden in CKD patients. Nontraditional risk factors, unique to CKD patients, include proteinuria, disturbed calcium, and phosphate metabolism, anemia, fluid overload, and accumulation of uremic toxins. This accumulation of uremic toxins is associated with systemic alterations including inflammation and oxidative stress which are considered crucial in CKD progression and CKD-related CVD. Kidney transplantation can mitigate the impact of some of these nontraditional factors, but they typically persist to some degree following transplantation. Taking into consideration the scarcity of data on uremic waste products, oxidative stress, and their relation to atherosclerosis in renal transplantation, in the review, we discussed the impact of uremic toxins on vascular dysfunction in CKD patients and kidney transplant recipients. Special attention was paid to the role of native and transplanted kidney function.

Parathyroid Hormone Profile In Sickle Cell Disease In School Aged Children

Background: Sickle cell disease (SCD) is group of hemoglobinopathies associated with hemolytic anemia and vasoocclusive complications. All forms of SCD are inherited in an autosomal recessive fashion. Parathyroid hormone plays an essential role in calcium and phosphorus homeostasis, which is achieved by its action on target organs (intestine, bone and kidney), leading to normal bone formation and mineralization and normal physiological concentration of calcium and phosphorus. Objectives: This study aimed to detect the effect of sickle cell disease on parathyroid hormone and consequently on serum calcium (S.Ca), phosphorus (ph), alkaline phosphatase (alk.Ph) and magnesium (Mg) on patients with sickle cell anemia. Subjects and Methods: Forty children known as sickle cell disease patients, twenty of them were SCD (HbSS) (11 males and 9 females). The other twenty were known SC trait (10 males and 10 females). The ages of the children ranged from 5 to 15 years old. All were in non-crises state in routine Outpatient Clinic visits, compared to twenty apparently healthy, age matched and with normal hemoglobin from Atfal Masr Hospital as control. Neither patients nor control received calcium supplementation before the study. Results: The results indicated that sickle cell patients and sickle cell trait patients had hypocalcaemic tendency associated with supernormal parathyroid hormone level and implied impaired calcium absorption from intestine leading to disturbed calcium metabolism, which might contribute in skeletal changes seen in sickle cell patients. Conclusion: We found that there was statistically significant decrease in serum Ca levels accompanied with increase in serum PTH, ph, alk Ph and Mg levels in SCD and Sickle cell trait patients compared to control group.

Osteodystrophies of jaws

Bone is a dense, semi rigid, porous, calcified connective tissue forming the major portion of the skeleton of most vertebrates. It consists of a dense organic matrix and an inorganic mineral component. Bone remodelling is a complex process by which old bone is continuously replaced by new tissue, which requires interaction between different cell phenotypes and is regulated by a variety of biochemical and mechanical factors. In a homeostatic equilibrium, the process of resorption and formation are balanced so that old bone is continuously replaced by new tissue and it adapts to mechanical load and strain. Several local and systematic factors which cause disturbances in bone resorption and deposition leads to abnormal or defective development of bone commonly termed as osteodystrophy - A defective ossification of bone usually is associated with disturbed calcium and phosphorus metabolism. The better understanding of molecular cellular biology and pathogenic mechanism aids to define the abnormalities in osteoblastic and osteoclastic lineages and to develop new therapeutic approaches.

Хондрокальциноз как ранний признак первичного гиперпаратиреоза

Objective: To deeply analyse a case of a patient with calcium pyrophosphate crystal storage disease, where chondrocalcinosis (CC) preceded primary hyperparathyroidism (PHPT). Key Points. The association of CC and hyperparathyroidism is well-known; and CC is recognised as one of the late signs of hyperparathyroidism. We describe a 67-year old patient with PHPT, presenting for a long time only with X-ray CC and chronic arthritis, associated with calcium pyrophosphate deposits. At the same time, he did not have any electrolyte imbalances, had normal serum calcium and parathyroid hormone levels; PHPT was diagnosed after 10 years of follow-up when the patient developed life-threatening hypercalcemia. It can be assumed that, unlike other musculoskeletal signs, CC can be one of the earliest symptoms of hyperparathyroidism. Treating CC as a late sign of hyperparathyroidism is likely to be associated with challenges of early diagnosis (asymptomatic in some patients, low sensitivity of X-ray diagnostics). In order to assess the diagnostic value of CC in hyperparathyroidism, including patients with normal calcium levels, specific tests are essential. Conclusion. Target examination for CC using highly-sensitive methods in patients with minor calcium metabolism disturbances, high/normal parathyroid hormone level or slightly increased parathyroid hormone level and normal calcium can improve the detection frequency of both CC and PHPT and follow-up of such patients. Early PHPT diagnosis (prior to clinical presentation) can help in preventing severe, life-threatening complications. Keywords: chondrocalcinosis, primary hyperparathyroidism, parathyroid hormone, calcium pyrophosphate crystal storage disease, hypercalcemia.

SAT-322 MISCLASSIFICATION OF CALCIUM STATUS IN END-STAGE KIDNEY DISEASE USING ALBUMIN-ADJUSTED CALCIUM LEVELS

Disturbed calcium metabolism and mineral bone disease (CKD-MBD) is a common development as patients approach end-stage kidney disease. Clinical laboratories measure total calcium and adjust for serum albumin concentrations to approximate ionised levels and help classify calcium status. The strength of relationship between corrected and ionised calcium weakens below serum albumin levels of 30g/L. Clinical treatment guidelines for CKD-MBD continue to recommend the use of albumin-adjusted calcium for monitoring despite ionised calcium being the biologically active fraction.

Relevance of early intervention in Fahr’s disease: understanding through a case study

Intracranial calcification may result from disturbances in calcium metabolism. It often remains asymptomatic, but may present with symptoms like seizure and neurological deficits. Correction of the underlying metabolic disturbance before...

Metabolic bone disease risk factors strongly contributing to long bone and rib fractures during early infancy: A population register study.

BackgroundThe aim of this study was to assess the incidence of fractures in infancy, overall and by type of fracture, its association with accidents, metabolic bone disease risk factors, and abuse diagnosis.MethodsThe design was a population-based register study in Sweden. Participants: Children born 1997–2014, 0–1 years of age diagnosed with fracture-diagnosis according to International Classification of Diseases (ICD10) were retrieved from the National Patient Register and linked to the Swedish Medical Birth Register and the Death Cause Register. Main outcome measures were fractures of the skull, long bone, clavicle and ribs, categorized by age (younger or older than 6 months), and accident or not.FindingsThe incidence of fractures during infancy was 251 per 100 000 infants (n = 4663). Major fracture localisations were long bone (44·9%), skull (31·7%), and clavicle (18·6%), while rib fractures were few (1·4%). Fall accidents were reported among 71·4%. One-third occurred during the first 6 months. Metabolic bone disease risk factors, such as maternal obesity, preterm birth, vitamin D deficiency, rickets, and calcium metabolic disturbances, had increased odds of fractures of long bones and ribs in early infancy (0–6 months): birth 32–36 weeks and long bone fracture [AOR 2·13 (95%CI 1·67–2·93)] and rib fracture [AOR 4·24 (95%CI 1·40–12·8)]. Diagnosis of vitamin D deficiency/rickets/disorders of calcium metabolism had increased odds of long bone fracture [AOR 49·5 (95%CI 18·3–134)] and rib fracture [AOR 617 (95%CI 162–2506)]. Fractures without a reported accident had higher odds of metabolic risk factors than those with reported accidents. Abuse diagnosis was registered in 105 infants, with overrepresentation of preterm births, multiple births and small-for-gestational age.InterpretationMetabolic bone disease risk factors are strongly associated with fractures of long bone and ribs in early infancy. Fracture cases with abuse diagnosis had a metabolic bone risk factor profile.

Groundwater contamination with cadmium concentrations in some West U.P. Regions, India.

Water is considered a vital resource because it is necessary for all aspects of human and ecosystem survival. However, due to natural processes and anthropogenic activities, various pollutants have been added to the ground water system. Among these, heavy metals are some of the most serious pollutants. Cd, a toxic heavy metal used in Ni-Cd batteries, the colouration of plastic and various discarded electronic products released into the water system causes serious health issues. The chronic exposure to Cd produces a wide variety of acute and chronic effects in humans. Cd accumulates in the human body, especially in the kidneys, resulting in kidney damage (renal tubular damage), which is a critical health effect. Other effects of Cd exposure are disturbances in calcium metabolism, hypercalciuria and the formation of kidney stones. High exposure to Cd can lead to lung cancer and prostate cancer; hence, poor quality water that may result in Cd toxicity has become a global concern. Thus, the aim of this study is to determine the concentration of Cd in underground water sources in western U.P. regions. Water samples were acidified to 1% with nitric acid and then stored in double-capped polyethylene bottles for further analysis by an atomic absorption spectrophotometer. After comparing the data to the WHO (2011) permissible limit, the study revealed that the concentration of Cd was higher than the regulatory threshold; therefore, the underground water system is seriously affected by Cd toxicity.

Modification of levosimendan-induced suppression of atrial natriuretic peptide secretion in hypertrophied rat atria

This study aimed to determine the effects of levosimendan, a calcium sensitizer, on atrial contractility and atrial natriuretic peptide (ANP) secretion and its modification in hypertrophied atria. Isolated perfused beating rat atria were used from control and isoproterenol-treated rats. Levosimendan and its metabolite OR-1896 caused a positive inotropic effect and suppressed ANP secretion in rat atria. Similar to levosimendan, the selective phosphodiesterase 3 (PDE3) or PDE4 inhibitor also suppressed ANP secretion. Suppression of ANP secretion by 1 µM levosimendan was abolished by PDE3 inhibitor, but reversed by PDE4 inhibitor. Levosimendan-induced suppression of ANP secretion was potentiated by KATP channel blocker, but blocked by KATP channel opener. Levosimendan alone did not significantly change cyclic adenosine monophosphate (cAMP) efflux in the perfusate; however, levosimendan combined with PDE4 inhibitor markedly increased this efflux. The stimulation of ANP secretion induced by levosimendan combined with PDE4 inhibitor was blocked by the protein kinase A (PKA) inhibitor. In isoproterenol-treated atria, levosimendan augmented the positive inotropic effect and ANP secretion in response to an increased extracellular calcium concentration ([Ca+]o). These results suggests that levosimendan suppresses ANP secretion by both inhibiting PDE3 and opening KATP channels and that levosimendan combined with PDE4 inhibitor stimulates ANP secretion by activating the cAMP–PKA pathway. Modification of the effects of levosimendan on [Ca+]o-induced positive inotropic effects and ANP secretion in isoproterenol-treated rat atria might be related to a disturbance in calcium metabolism.