Chromosomal Aberrations, Micronuclei, Blood Parameters and Received Doses in Workers Exposed to Ionizing Radiation.

BACKGROUND: The aim of this study was to analyze the impact of low doses of ionizing radiation on healthcare workers using dosimeter data and several biomarkers of effects, and to asses the suitability of those tests. METHODS: Data from the last medical examinations, obtained from the medical records of 148 employees were analysed. They were divided into three groups: nuclear medicine, interventional radiology and general radiology. The examination included hematological parameters and cytogenetical tests: unstable chromosomal aberrations (UCA) and micronucleus test (MNT). The received cumulative 5-year dose was calibrated into personal dose equivalents Hp(10). RESULTS: A statistically significant difference was found between the groups in the UCAs (c2=6.634, p=0.036) with the highest UCA frequency in nuclear medicine. The ANOVA showed a statistically significant difference in the values of erythrocytes (F(2,140)=3.715, p=0.027), monocytes (F(2,127)=3.326, p=0.039) and platelets (F(2,135)=4.209, p=0.017), with higher erythrocytes and lower platelets in interventional radiology and lower monocytes in nuclear medicine, all with small effect size. The dose was significantly different among the groups (c2 =22,191; p<0.001). The nuclear medicine workers received a higher dose compared to interventional radiology (U=458, p<0.001) and general radiology (U=510.5, p<0.001). CONCLUSIONS: Nuclear medicine employees are at a higher risk of developing neoplastic and blood-related diseases due to consistent exposure to low doses of ionizing radiation. Results suggest that UCA test might be more suitable for detecting radiation-induced damage at low doses than MNT. Compulsory monitoring of the health status at periodic examinations is required to prevent occupational diseases, esp. among the nuclear medicine workers.

Preventive treatment with dizocilpine attenuates oedema in a carrageenan model of inflammation: the interaction of glutamatergic and nitrergic signaling.

Dizocilpine is a highly selective and potent non-competitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor. It is well known that dizocilpine has different neuroprotective effects in animal models of pain, epilepsy and oedema during trauma. The search for alternative antiinflammatory drugs is ongoing. We investigated the anti-oedematous effects of dizocilpine and the probable mechanism of action in a rat model that mimics local and persistent inflammation without tissue injury or damage. Male Wistar rats were injected with 100 µL of 0.5% carrageenan to the plantar surface of the hind paw. Anti-oedematous activity was assessed in the carrageenan-induced paw inflammatory oedema test with a plethysmometer. To assess possible mechanisms of dizocilpine action, we examined the effects of the selective inhibitor of neuronal [N-ω-propyl-L-arginine hydrochloride (L-NPA)] and inducible [S-methylisothiourea (SMT)] nitric oxide synthase (NOS). Dizocilpine after systemic (0.0005, 0.005 and 0.02 mg/kg, subcutaneous (s.c.)), but not after local peripheral administration, reduced the paw inflammatory oedema. The effect is not dose dependent, and the highest decrease by about 47% at the time of maximally developed oedema was achieved with 0.005 mg/kg. Intraperitoneally (i.p.) administered L-NPA (0.5, 1 and 2 mg/kg) or SMT (0.005, 0.01 and 0.015 mg/kg) before dizocilpine abolished or reduced the anti-oedematous effect of dizocilpine by about 70-85%. An acute single dose of dizocilpine administered before inducing oedema systemically reduced the development of inflammatory oedema. The mechanism of the anti-oedematous effect includes, at least partially, an increase in nitric oxide (NO) production.

Micronuclei as a marker for medical screening of subjects continuously occupationally exposed to low doses of ionizing radiation.

CONTEXT: Genotoxicity assays are widely employed in human biomonitoring studies to assess genetic damage inflicted by genotoxic agents. OBJECTIVE: Evaluation of micronuclei (MN) as a screening marker of occupational ionizing radiation (IR) exposure. MATERIALS AND METHODS: Using micronucleus test, peripheral blood lymphocytes (PBL) of 402 control and exposed subjects were screened for genetic damage. RESULTS: The mean frequencies of micronucleus test parameters were significantly higher in exposed persons. Increase of micronucleus yield with duration of exposure (DOE) by 0.303MN/year was revealed. DISCUSSION AND CONCLUSION: The obtained data encourage us to consider MN as valuable markers for preventive medical screening of occupationally exposed groups.

Screening commercial drivers for obstructive sleep apnea: translation and validation of Serbian version of Berlin Questionnaire.

PURPOSE: Obstructive sleep apnea (OSA) can lead to severe health consequences. Drivers of motor vehicles with untreated or undiagnosed OSA have a greater risk of traffic accidents. Use of self-reported questionnaires is the first step in OSA diagnosis. The main aim of this study was to perform the translation and validation of Berlin Questionnaire in a sample of commercial drivers. METHODS: After formal translation, validation was performed on a sample of commercial drivers and included evaluation of internal consistency, test-retest reliability, construct and criterion validity. Full-night attended polysomnography or cardiorespiratory polygraphy was used for OSA diagnosis. RESULTS: One hundred male participants, 24-62 years old, were included. Berlin Questionnaire classified 35 % subjects as potential OSA patients. Polysomnography confirmed OSA in 58 % of the subjects. Berlin Questionnaire showed good internal consistency (Cronbach's alpha 0.82-first category, 0.73-0.95-second category). Test-retest reliability (Cohen's kappa 0.78) was adequate. Berlin score was significantly correlated with OSA category and apnea-hypopnea index (AHI). Sensitivity of Berlin Questionnaire was from 50.9 (AHI ≥ 5) to 75 % (AHI ≥ 30), while specificity ranged from 86 to 70.5 %. CONCLUSIONS: Berlin Questionnaire (Serbian version) showed good measurement properties, creating basis for further research of its usefulness as OSA screening tool in populations of interest.

A cytogenetic study of hospital workers occupationally exposed to radionuclides in Serbia: premature centromere division as novel biomarker of exposure?

PURPOSE: The health risk of chronic exposure to radionuclides includes changes in the genome (e.g., chromosomal aberrations and micronuclei) that increase chromosomal instability. There are also other phenomena, which seem to appear more frequently in metaphases of exposed persons (such as premature centromere division). The aim of this study was to discover whether or not there is correlation between incidence of named cytogenetic changes in persons occupationally exposed to radionuclides in comparison with unexposed control group, and if significant correlation is determined, can premature centromere division be consider as a biomarker of radiation exposure? METHODS: The exposed group comprised 50 individuals occupationally exposed to radionuclides. The reference control group consisted of 40 unexposed individuals. Chromosomal aberrations, micronuclei and premature centromere division were analyzed according to a standard International Atomic Energy Agency protocol. Statistical analyses were performed using SPSS 17.0 statistics. RESULTS: The means for analyzed cytogenetic changes were significantly higher in the exposed group. Positive correlation between them was found in exposed group. Premature centromere division parameter PCD5-10 was selected as particularly suitable for separating groups (exposed/unexposed). CONCLUSIONS: Identification of other phenomena related to radionuclide exposure, beside well known, may clarify recent problems in radiobiology concerning the biological response to low doses of ionizing radiation and its consequences.

Immunolocalization of the TASK2 Potassium Channel in Frog Kidney.

TASK2 (K2P5. 1, KCNK5) is a two-pore domain K⁺ channel belonging to the TALK subgroup of the K2P family of proteins. TASK2 expression has been reported in a variety of cells and tissues ranging from kidney to immune cells and including specific neurons, its proposed functions spanning from involvement in the regulation of cell volume to control of excitability. The purpose of this study was to determine the tubule location ofthe TASK2 K⁺ channel protein in frog kidney applying polyclonal antibody against the carboxyl terminus of human TASK2 (KCNK5) protein. Immunohistochemical analysis revealed that TASK2 is expressed on distal tubules and proximal epithelial cells. TASK2 is strongly expressed predominantly on the luminal part ofthe proximal epithelial cells and slightly cytoplasmatic staining is expressed. Distal tubules showed diffuse cytoplasmatic staining as well as slight staining on the apical parts ofthe cells. These findings suggest that the TASK2 K⁺ channel has cell-specific roles in renal potassium ion transport.

Inter-individual variability in the response of human peripheral blood lymphocytes to ionizing radiation: comparison of the dicentric and micronucleus assays.

Ionizing radiation can induce a wide range of DNA damage that leads to chromosomal aberrations. Some of those aberrations (dicentrics and micronuclei) are applied in biodosimetry. Biological dosimetry assumes similar radiosensitivity of each donor, but it does not exclude inter-individual variations in radiation susceptibility. Therefore, for biological reasons, it is always challenging to investigate inter-individual variability in response to radiation. For mechanistic reasons, it is also interesting to investigate the correlation between dicentric and micronuclei formation in response to radiation. In this experiment, irradiated blood specimens from 14 healthy male and female donors have been used to evaluate inter-individual variability in response to the genotoxic effects of X-ray radiation, as well as the dose-response relationship and test sensitivity using two endpoints (dicentrics and micronuclei). The results showed similar patterns of cytogenetic biomarker distribution between donors, but differences in the response of some donors at some doses. Data also showed that responses of male donors were better detected using the dicentric test, while for females, micronucleus frequencies were higher in response to the same dose of radiation. No influence of smoking status or age on specific responses was observed. Group variability in response to radiation was evaluated using coefficient of variation for each group of individuals irradiated with the same doses; as the dose increases, group variability becomes substantially lower. Despite sporadic inter-individual variability, trend of radiation-induced changes was similar. Produced calibration curves for both types of damage revealed dicentrics as genetic damage more typical for radiation than micronuclei.

Accuracy of analytically determined fractional flow reserve derived from coronary angiography for non-invasive assessment of coronary artery stenosis.

BACKGROUND: Fractional flow reserve (FFR) determined invasively has been globally accepted as the gold standard for determining the functional significance of coronary artery stenoses. However, despite its great importance, the invasive method has certain disadvantages, including the risk of vascular injuries, the need for vasodilation, and significant medical costs. That is why great attention was paid to the development of non-invasive methods that would enable reliable diagnosis without exposing patients to the risk of unwanted consequences. OBJECTIVE: This paper aimed to create and verify an alternative, less resource- and time-demanding, non-invasive solution. METHODS: The determination of FFR is based on the application of the fundamental laws of fluid dynamics. All energy losses in the coronary artery with stenosis were identified and analyzed in detail. A three-dimensional model of a coronary artery was generated using the corresponding angiographic images. Finally, the pressure due to stenosis was calculated and the FFR was determined. RESULTS: The results obtained using the proposed analytical method were compared with available experimental data for 40 patients who experienced the invasive coronary angiography. The coefficient of determination, mean difference and standard deviation values are determined to be 0.726, -0.017 and 0.056, respectively. These values were slightly higher for FFR values above 0.80. CONCLUSION: The FFR calculated by the proposed analytical method has a relatively good correlation with clinical data, which leads to the conclusion that it can provide a reliable assessment of the functional significance of coronary stenosis.

Morphometric analysis of Ki-67 and p16 expression in laryngeal precursor lesions.

Laryngeal precursor lesions represent areas of altered epithelium with an increased likelihood for progression to squamous cell carcinoma. The exact molecular mechanisms of malignant transformation of laryngeal mucosa are not completely clear, but are certainly due to deregulation of cell proliferation. To assess the potential value of the p16 and Ki-67 as markers of malignant progression, we undertook a retrospective immunohistochemical and morphometric analysis on biopsy specimens from patients with precancerous lesions in the larynx. Morphometric analysis of samples stained with p16 antibody showed epithelial cell positivity in 29 (100 %) of samples with simple hyperplasia, 31 (100 %) samples with basal/parabasal cell hyperplasia, 23 (88 %) samples with atypical hyperplasia and 20 (95 %) samples with in situ carcinoma. There was a significant difference in percentage of p16-positive cells between samples with simple hyperplasia and samples with in situ carcinoma. Morphometric analysis of samples stained with Ki-67 antibody showed epithelial cell positivity in 27 (93 %) of samples with simple hyperplasia, 30 (97 %) samples with basal/parabasal cell hyperplasia, 26 (100 %) samples with atypical hyperplasia and 18 (86 %) samples with in situ carcinoma. There was a significant difference not only in the percentage of Ki-67-positive cells between samples with simple hyperplasia and samples with in situ carcinoma, but also between samples with simple and basal/parabasal cell hyperplasia. Laryngeal epithelial precursor lesions show significantly opposite patterns in p16 and Ki-67 immunopositivity. Simple hyperplasia on average shows 12 % of Ki-67-positive cells and 46 % of p16-positive cells. In situ carcinoma on average shows 23 % of Ki-67-positive cells and 36 % of p16-positive cells.

Numerical vs analytical comparison with experimental fractional flow reserve values of right coronary artery stenosis.

BACKGROUND: The fractional flow reserve (FFR) index has been widely accepted as a standard diagnostic method for identifying functional relevance of coronary stenosis. Since the invasive techniques used for its determination are associated with a certain risk of vascular injury, as well as with an increased cost, several non-invasive procedures have been developed. OBJECTIVE: The aim of this study was to compare FFR values for the coronary artery obtained by computational fluid dynamics (CFD) and coronary computed tomography angiography (CCTA). METHODS: Computation of FFR has been performed using both numerical and the analytical method. The numerical method employs CFD to solve the governing equations which relate to mass and momentum conservation (the continuity equation and the Navier-Stokes equations) as well as CCTA to generate the three-dimensional computational domain. After imposing the appropriate boundary conditions, the values of the pressure change are calculated and the FFR index is determined. Based on Bernoulli's law, the analytical method calculates the overall pressure drop across the stenosis in the coronary artery, enabling FFR determination. RESULTS: The clinical data for twenty patients who underwent invasive coronary angiography are used to validate the results obtained by using CFD (together with CCTA) simulation and analytical solution. The medically measured FFR compared to the analytical one differs by about 4%, while, the difference is about 2.6% when compared to the numerical FFR. For FFR values below 0.8 (which are considered to be associated with myocardial ischemia) the standard error has a value of 0.01201, while the standard deviation is 0.02081. For FFR values above 0.80, these values are slightly higher. Bland-Altman analysis showed that medical measurement and numerical FFR were in good agreement (SD = 0.0292, p< 0.0001). CONCLUSIONS: The analytically calculated FFR has a slightly lower coefficient of determination than the numerically computed FFR when compared with experimental one. However, it can still give a reliable answer to the question of whether patients need a stent, bypass surgery or only drug treatment and it requires a significantly lower computation time.

Biological response to the continuous occupational exposure to antineoplastic drugs and radionuclides.

PURPOSE: Antineoplastic drugs and radioiodine are recognized occupational risk factors affecting the genetic material of exposed persons. To assess cytogenetic damage and evaluate the presence of chromosomal instability during occupational exposure, a biomonitoring study was performed using a chromosomal aberration assay and a cytokinesis-block micronucleus (CBMN) test. MATERIALS AND METHODS: Blood samples from 314 healthy donors divided into 3 groups (control, exposed to antineoplastic drugs and exposed to radioiodine) were collected and cytogenetically analyzed. RESULTS: There was an increase in almost all analyzed parameters registered in the exposed persons. Chromatid breaks were higher in the subjects exposed to antineoplastic drugs, while dicentrics and premature centromere division (PCD) parameters were higher in nuclear medicine workers. The total number of micronuclei was higher in both groups of the exposed. The correlation analysis indicated the association of dicentrics, acentrics, chromosome and chromatid break with PCDs in both groups of the exposed, and micronuclei and nucleoplasmic bridges with PCDs in the subjects exposed to radioiodine. The discriminant analysis marked off PCD1-5 as the best predictor of exposure. Age, sex, sampling season and duration of exposure significantly influenced the analyzed parameters, while smoking habits did not show any influence. CONCLUSION: Based on the observed results, premature centromere division can be considered a valuable parameter of genotoxic risk for individuals occupationally exposed to low doses of ionizing radiation.

Serum Concentration of Prostaglandin E2 as a Diagnostic Biomarker in Patients With Silicosis: A Case-Control Study.

OBJECTIVE: Silicosis is a prevalent incurable pneumoconiosis caused by inhalation of silica dust. Study aimed to investigate inflammatory, hematological, and biochemical parameters as additional biomarkers for diagnosing or monitoring silicosis. METHODS: Research enrolled 14 workers with silicosis and 7 healthy controls (without exposure and silicosis). The serum level of prostaglandin E2, C-reactive protein, fibrinogen, biochemical, and hematological parameters were measured. The receiver operating characteristic curve was used to determine diagnostic sensitivity of each biomarker. RESULTS: Patients with silicosis have a significantly higher level of prostaglandin E2, erythrocyte, hemoglobin, and hematocrit than patients without silicosis. Prostaglandin E2, hemoglobin, and the erythrocyte count are significant in separating the silicosis cases from healthy controls. CONCLUSIONS: Prostaglandin E2 might be an adjuvant peripheral diagnostic biomarker for silicosis, while hematological parameters (erythrocytes, hemoglobin, and hematocrit) might be prognostic biomarkers.

The simultaneous action of acute paradoxical sleep deprivation and hypothyroidism modulates synaptosomal ATPases and acetylcholinesterase activities in rat brain.

BACKGROUND: Thyroid dysfunctions as well as sleep abnormalities are usually followed by neurological, psychiatric and/or behavioral disorders. On the other hand, changes in the brain adenosine triphosphatases (ATPases) and acetylcholinesterase (AChE) activities show significant importance in pathogenetic pathways in the evolution of numerous neuropsychiatric diseases. METHODS: This study aimed to evaluate the in vivo simultaneous effects of hypothyroidism and paradoxical sleep deprivation for 72 h on synaptosomalATPases and AChE activities of whole rat brains. In order to induce hypothyroidism, 6-n-propyl-2-thiouracil was administrated in drinking water during 21 days. The modified multiple platform method was used to induce paradoxical sleep deprivation. The AChE and ATPases activities were measured using spectrophotometric methods. RESULTS: Hypothyroidism significantly increased the activity of Na+/K+-ATPase compared to other groups, while at the same time significantly decreased AChE activity compared to the CT and SD groups. Paradoxical sleep deprivation significantly increased AChE activity compared to other groups. The simultaneous effect of hypothyroidism and sleep deprivation reduced the activity of all three enzymes (for Na+/K+-ATPase between HT/SD and HT group p < 0.0001, SD group p < 0.001,CT group p = 0.013; for ecto-ATPases between HT/SD and HT group p = 0.0034, SD group p = 0.0001, CT group p = 0.0007; for AChE between HT/SD and HT group p < 0.05, SD group p < 0.0001, CT group p < 0.0001). CONCLUSIONS: The effect of simultaneous existence of hypothyroidism and paradoxical sleep deprivation reduces the activity of the Na+/K+-ATPase, ecto-ATPases, and AChE, what is different from individual effect of hypothyroidism and paradoxical sleep deprivation itself. This knowledge could help in the choice of appropriate therapy in such condition.

Associations of burnout with job demands/resources during the pandemic in health workers from Southeast European countries.

Introduction: Despite several studies assessing job demands and burnout in countries from the Southeast European (SEE) region, there is still a lack of data about the psychological impact of the pandemic on health workers (HWs). Aims: The present study aimed to demonstrate and compare levels of burnout dimensions in HWs from SEE countries and to reveal the burnout-job demands/resources relationships in these workers during the pandemic. Materials and methods: During the autumn of 2020, this online multicentric cross-sectional survey studied a large group (N = 4.621) of HWs working in SEE countries. The Maslach Burnout Inventory was used for the measurement of burnout dimensions. We analyzed the job demands by using the Hospital Experience Scale. Remuneration and relationships with superiors were measured using the Questionnaire sur les Ressources et Contraintes Professionnelles (English version). Results: A series of ANOVA comparisons of means revealed the countries in which respondents showed higher mean values of emotional exhaustion (Bosnia and Herzegovina, Bulgaria, Croatia, Moldova, Montenegro, and North Macedonia) and the countries in which respondents showed lower mean values of this burnout dimension (Israel and Romania) (Welch F = 17.98, p < 0.001). We also found differences among HWs from different countries in job demands and job resources. The testing of hierarchical regression models, which have been controlled for certain confounding factors, clearly revealed that emotional exhaustion was predicted by job demands (R2 = 0.37) and job resources (R2 = 0.16). Conclusion: Preventive measures for the improvement of mental health in HWs during the pandemic and beyond have to take into account the differences between countries regarding the country context and current scientific knowledge. A modified stress test should be implemented in hospitals regarding future shocks that might include new pandemics, terrorism, catastrophes, or border conflicts.

Gallbladder motility disorders estimated by non-invasive methods.

BACKGROUND/AIMS: The aim is to compare the radionuclide (DC) and ultrasonographic (US) method in the assessment of gallbladder (GB) motility. METHODOLOGY: The study was performed in 15 controls (C), 10 patients with acute cholecystitis (AC), 20 patients with chronic acalculous cholecystitis (CAC), 26 patients with chronic cholecystitis with calculosis (CCC) as well as in 15 patients with GB dyskinesia (D). GB emptying period (EP), ejection fraction (EF) and ejection rate (ER) were estimated with dynamic cholescintigraphy (DC) and US. RESULTS: The DC and US finding in the patients with AC was typical in all the patients, i.e. GB was not visualized at all on DC, while on US, stone was visible in the cystic duct. There were significant differences (p<0.05) between the EF and ER values obtained between C and the three groups of patients CAC, CCC and D, using both methods. However, there were no significant differences in EF, EP and ER values among CAC, CCC and D (p>0.05). There was also high correlation between the results obtained with both methods in all the groups of patients studied. CONCLUSIONS: The results obtained by both methods are valuable for the assessment of GB motility. Although there are no significant differences and there is a high correlation between the values, radionuclide method is more precise, because it can register motility continuously.

Diagnosis of mesh infection after abdominal wall hernia surgery - role of radionuclide methods.

BACKGROUND/AIMS: The aim of this investigation was to evaluate the role of detection of late mesh infection following incisional hernia repair with radiolabeled antigranulocyte antibodies. METHODOLOGY: Mesh infection diagnoses were set up with clinical examination and laboratory analysis and confirmed by ultrasonography (US), computerized tomography (CT), scintigraphy with 99mTc-antigranulocyte antibodies and microbiological examination. RESULTS: Of the 17 patients investigated, 6 had a late mesh infection, and 11 had both mesh infection and recurrent incisional hernia. Clear clinical signs of late mesh infection were present in 13 patients. Four remaining patients had non-specific discomfort and recurrent incisional hernia without clinical manifestation of mesh infection ('silent infection'). US was positive in 12/17 patients, CT in 13/17 patients, while scintigraphy with antigranulocyte antibodies in 17/17 patients. Therefore, sensitivity of US was 71%, of CT 76% and of scintigraphy 100%. In four patients late mesh infection was confirmed exclusively by 99mTc-antigranulocyte antibody scintigraphy, while US and CT did not indicate the infection. CONCLUSIONS: According to the present results, scintigraphy with 99mTc antigranulocyte antibodies is a useful method for the detection of 'silent' abdominal wall infections after surgery, which is very important for prompt and appropriate therapy.

Low-level laser therapy for acute neck pain with radiculopathy: a double-blind placebo-controlled randomized study.

OBJECTIVE: The objective of the study was to investigate clinical effects of low-level laser therapy (LLLT) in patients with acute neck pain with radiculopathy. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: The study was carried out between January 2005 and September 2007 at the Clinic for Rehabilitation at the Medical School, University of Belgrade, Serbia. PATIENTS AND INTERVENTION: Sixty subjects received a course of 15 treatments over 3 weeks with active or an inactivated laser as a placebo procedure. LLLT was applied to the skin projection at the anatomical site of the spinal segment involved with the following parameters: wavelength 905 nm, frequency 5,000 Hz, power density of 12 mW/cm(2), and dose of 2 J/cm(2), treatment time 120 seconds, at whole doses 12 J/cm(2). OUTCOME MEASURES: The primary outcome measure was pain intensity as measured by a visual analog scale. Secondary outcome measures were neck movement, neck disability index, and quality of life. Measurements were taken before treatment and at the end of the 3-week treatment period. RESULTS: Statistically significant differences between groups were found for intensity of arm pain (P = 0.003, with high effect size d = 0.92) and for neck extension (P = 0.003 with high effect size d = 0.94). CONCLUSION: LLLT gave more effective short-term relief of arm pain and increased range of neck extension in patients with acute neck pain with radiculopathy in comparison to the placebo procedure.

Modulation of luminal L-alanine transport in proximal tubular cells of frog kidney induced by low micromolar Cd2+ concentration.

The kidneys are recognized as a major target of cadmium-induced toxicity. However, all mechanisms that are involved in the early stages of cadmium nephrotoxicity, particularly considering low micromolar concentrations of cadmium ions (Cd2+) are still unknown. Therefore, the aim of this study was to investigate the effects of peritubular acute exposure to micromolar Cd2+ concentration (2.3 µmol/L) on the rapid depolarization and the rate of slow repolarization of peritubular membrane potential difference (PD), induced by luminal application of L-alanine in proximal tubular cells of frog kidney. The results showed that the luminal application of L-alanine rapidly depolarized the peritubular membrane PD of -42.00 ±â€¯11.68 mV by 23.89 ±â€¯4.15 mV with an average rate of slow repolarization of 5.64 ±â€¯0.81 mV/min. Additionally, peritubular acute exposure to Cd2+ induced change in rapid depolarization of peritubular membrane PD of -53.33 ±â€¯13.01 mV by 18.78 ±â€¯3.31 mV (P < 0.01) after luminal application of L-alanine. Also, peritubular acute exposure to Cd2+ led to statistically significant decrease in the rate of slow repolarization of peritubular membrane PD (3.53 ±â€¯0.35 mV/min; P < 0.05). In conclusion, these results suggest that peritubular acute exposure to low micromolar Cd2+ concentration decreased the rapid depolarization and the rate of slow repolarization of peritubular membrane PD induced by luminal application of L-alanine. This is followed by reduced luminal sodium-coupled transport of L-alanine and this change may be one of the possible mechanisms involved in the early stages of Cd2+-induced nephrotoxicity.

Low micromolar concentrations of cadmium and mercury ions activate peritubular membrane K+ conductance in proximal tubular cells of frog kidney.

The present study was designed to investigate the acute effects of extracellular low micromolar concentrations of cadmium and mercury ions on the peritubular cell membrane potential and its potassium selectivity in proximal tubular cells of the frog kidney. Peritubular exposure to 3 micromol/L Cd(2+) or 1 micromol/L Hg(2+) led to a rapid, sustained and reversible hyperpolarization of the peritubular cell membrane, paralleled by an increase in fractional K(+) conductance. Peritubular barium abolished hyperpolarization of the peritubular cell membrane to peritubular 3 micromol/L Cd(2+) or 1 micromol/L Hg(2+). Perfusing the lumen with 10 mmol/L l-alanine plus/minus 3 micromol/L Cd(2+) or Hg(2+) did not modify rapid depolarization and rate of slow repolarization of the peritubular cell membrane potential. In conclusion, low micromolar concentrations of Cd(2+) and Hg(2+) increase K(+) conductive pathway in the peritubular cell membrane and in this way can enhance ability of proximal renal tubular cells to maintain the driving force for electrogenic Na(+) and substrate reabsorption.

Anthropological aspect of death in dialyzed patients.

The aim of this article is to compare the incidence of thanatophobia in dialysed patients having Balkan endemic nephropathy (BEN) with a control group (N18) members where some of them have chronic renal failure (CRF), but not (BEN). We examined thanatophobia on a sample of 753 dialysed patients with chronic renal failure (CRF) in Bosnia and Herzegovina (B&H) during the period from 1st January 2000 to 31st December 2006. The first group is a cohort consisted of 348 patients with Balkan endemic nephropathy (BEN), and the control group consisted of 405 randomly selected patients with different diagnoses of CRF (N18). The measurement instruments used were: General data list, Eysenck's Personality Questionnaire (EPQ), Beck's Anxiety Inventory (BAI), Hamilton's Depression Rating Scale (HDRS), and Mini-Mental State Examination (MMSE). Univariante and multivariante statistical analyses were carried out. From the multivariante analysis, the highest correlations with thanatophobia were found in these variables: avoidance of dialysis in BEN group: R=0.985, OR=0.358, CI=0.483-0.728 (95%), and in control group: R=0.550, OR=0.935, CI=0.615-0.830 (95%), age, years on dialysis, education, pervasive fear with statistical significance P=0.001. BEN group differentiates from control group: BAI-total (R=1.110, OR=0.578 (95%), CI=0.770-0.890, P=0.001), HDRS-total (R=0.995, OR=1.290 (95%), CI=1.180-1.920 P=0.001. BEN group have lower scores than the control group in MMSE-total: (R=0.430, OR=0.023 (95%), CI=0.034-2.850, P=0.001) which represents the organic part of anxiety. Thanatophobia is present in both groups, but it is more frequent in the BEN (11.70%) than in control group (7.50%). We found that thanatophobia occurs before dialysis, and that it is structured as a pervasive fear of death and is associated with endemia, years spent on dialysis, and avoidance of dialysis.