The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis.

Mycophenolate mofetil (MMF) is applied in proteinuric kidney diseases, but the exact mechanism of its effect on podocytes is still unknown. Our previous in vitro experiments suggested that MMF can ameliorate podocyte damage via restoration of the Ca2+-actin cytoskeleton axis. The goal of this study was to characterize podocyte biology during MMF treatment in nephrotoxic serum (NTS) nephritis (NTN). NTN was induced in three-week old wild-type mice. On day 3, half of the mice were treated with MMF (100 mg/kgBW/d p.o.) for one week. On day 10, we performed proteomic analysis of glomeruli as well as super-resolution imaging of the slit diaphragm. For multiphoton imaging of Ca2+ concentration ([Ca2+]i), the experimental design was repeated in mice expressing podocyte-specific Ca2+ sensor. MMF ameliorated the proteinuria and crescent formation induced by NTS. We identified significant changes in the abundance of proteins involved in Ca2+ signaling and actin cytoskeleton regulation, which was further confirmed by direct [Ca2+]i imaging in podocytes showing decreased Ca2+ levels after MMF treatment. This was associated with a tendency to restoration of podocyte foot process structure. Here, we provide evidence that MPA has a substantial direct effect on podocytes. MMF contributes to improvement of [Ca2+]i and amelioration of the disorganized actin cytoskeleton in podocytes. These data extend the knowledge of direct effects of immunosuppressants on podocytes that may contribute to a more effective treatment of proteinuric glomerulopathies with the least possible side effects.

Percutaneous CT-Guided Biopsies of the Cervical Spine: Technique, Histopathologic and Microbiologic Yield, and Safety at a Single Academic Institution.

BACKGROUND AND PURPOSE: Cervical spine biopsies can be challenging due to the anatomy and the adjacent critical structures. Percutaneous image-guided biopsies can obviate the need for an open biopsy, however there have been few studies looking at the approaches, safety, and efficacy of percutaneous cervical spine biopsies. This retrospective study evaluated technical considerations, histopathologic and microbiologic yield, and safety in CT-guided cervical bone biopsies. MATERIALS AND METHODS: A retrospective review of cervical bone and/or bone/disc biopsies performed from January 2010 to January 2017 was included in this study. Clinical diagnosis and indication, patient demographics, biopsy location, biopsy needle type, technical approach, lesion size, dose-length product, conscious sedation details, complications, and diagnostic histopathologic and/or microbiologic yield were recorded for each case and summarized. RESULTS: A total of 73 patients underwent CT-guided cervical bone biopsies. Fifty-three percent (39/73) were for clinical/imaging concern for infection and 47% (34/73) were for primary tumors or metastatic disease. Thirty-four percent (25/73) were of the inferior cervical spine (ie, C6 and C7). A sufficient sample was obtained for histopathologic and microbiologic analyses in 96% (70/73) of the biopsies. Forty-six percent (18/39) of those samples taken for infection had positive cultures. Two intraprocedural complications occurred in which the patients became hypotensive during the procedure without long-term complications. CONCLUSIONS: Percutaneous CT-guided biopsy of the cervical spine is an effective and safe procedure with high diagnostic yield and can obviate open procedures for histopathologic and microbiologic analyses of patients with clinical and imaging findings concerning for infection or primary and metastatic osseous lesions.

Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep.

Impaired sleep and enhanced stress hormone secretion are the hallmarks of stress-related disorders, including major depression. The central neuropeptide, corticotropin-releasing hormone (CRH), is a key hormone that regulates humoral and behavioral adaptation to stress. Its prolonged hypersecretion is believed to play a key role in the development and course of depressive symptoms, and is associated with sleep impairment. To investigate the specific effects of central CRH overexpression on sleep, we used conditional mouse mutants that overexpress CRH in the entire central nervous system (CRH-COE-Nes) or only in the forebrain, including limbic structures (CRH-COE-Cam). Compared with wild-type or control mice during baseline, both homozygous CRH-COE-Nes and -Cam mice showed constantly increased rapid eye movement (REM) sleep, whereas slightly suppressed non-REM sleep was detected only in CRH-COE-Nes mice during the light period. In response to 6-h sleep deprivation, elevated levels of REM sleep also became evident in heterozygous CRH-COE-Nes and -Cam mice during recovery, which was reversed by treatment with a CRH receptor type 1 (CRHR1) antagonist in heterozygous and homozygous CRH-COE-Nes mice. The peripheral stress hormone levels were not elevated at baseline, and even after sleep deprivation they were indistinguishable across genotypes. As the stress axis was not altered, sleep changes, in particular enhanced REM sleep, occurring in these models are most likely induced by the forebrain CRH through the activation of CRHR1. CRH hypersecretion in the forebrain seems to drive REM sleep, supporting the notion that enhanced REM sleep may serve as biomarker for clinical conditions associated with enhanced CRH secretion.

[Decrease in cardiovascular disease mortality in the Czech Republic from 1984 to 1993 and its possible causes]. / Pokles úmrtnosti na kardiovaskulární onemocnení v Ceské republice v období 1984-1993 a jeho mozné príciny.

BACKGROUND: The objective of the investigation was to evaluate the ten-year development of the cardiovascular mortality rate in two population groups in the age bracket from 25 to 64 years, i.e. in subjects living in six districts which participated in the international WHO project MONICA and in the population of the whole Czech Republic. METHODS AND RESULTS: Data on the mortality rate in 1984-1993 for the age group from 25-64 years were provided by the Institute of Health Information and Statistics, information on the prevalence of risk factors was obtained in three cross-sectional studies implemented in six districts as part of the MONICA project in 1985, 1988 and 1992. In the mortality rate per 100,000 population in the six districts the following changes were revealed (in parentheses the values for 1984 and 1993 are given): men - a statistically significant declining trend in the from all caused mortality (849.3-742.5; p < 0.001) and cardiovascular mortality (367.2-280.4; p < 0.001) and cerebrovascular mortality (69.7-44.8; p < 0.001). In the mortality from ischaemic heart disease (215.7-170.6; ns) a declining trend was not recorded. In women aged 25-64 years in the six districts there was a statistically significant decline of the mortality from all caused (359.5-322.1; p < 0.001), the cardiovascular mortality (115.6-100.6; p < 0.001) and cerebrovascular mortality (31.1-23.6; p < 0.001). The mortality from ischaemic heart disease did not change (49.2-48.8; ns). In the population of the Czech Republic in men the following were detected: a drop of the from all caused mortality (907.1-784.8; P < 0.001), the cardiovascular mortality (383.5-308.4; p < 0.001) and cerebrovascular mortality (76.5-55.3; p < 0.001). Also in women of the Czech Republic a decline of the mortality from all caused was recorded (390.1-328.5; p < 0.001), the cardiovascular mortality (135.3-103.8; p < 0.001), ischaemic heart disease (58.0-48.6; p < 0.001) and cerebrovascular mortality (43.5-27.4; p < 0.001). In 1990 an increased cardiovascular mortality was recorded in men different from the trend during 1984-1993, statistically significant in the Czech Republic (p < 0.05) and in the six districts (p < 0.05). The reasons of this trend are not clear. The role of health services in the mortality drop is not clear, although available data indicate their improvement. Favourable changes were found in risk factors: during the period from 1985-1992 the prevalence of hypercholesterolaemia declined significantly in men and women, the prevalence of hypertension in women and the prevalence of smoking in men declined in the six districts. From nationwide data ensues that after 1989 significant changes occurred in the diet of the Czech population. The meat consumption declined by 1993 by 13%, the milk and dairy product consumption by 26.8% the butter consumption by 43.6% the consumption of vegetable fats increased by 16%, of vegetables by 8%, tropical fruit by 43.2%. These changes probably had an impact on the cholesterol level and BMI of the Czech population. CONCLUSIONS: In the declining cardiovascular mortality trend during 1984-1993 the following may have participated: improved medical care, dietary changes, improvement of the risk profile and other, in particular socioeconomic factors. With regard to the close temporal association of the investigated changes it may be assumed that this development is at least partly associated with changes of the political and economic position in the Czech Republic after 1989.

[Is the recent decrease in cholesterolemia in the Czech Republic convincing evidence?]. / Je nedávný pokles cholesterolémie v Ceské republice prukazný?

BACKGROUND: The objective of the study was to evaluate the 8-year trend of serum cholesterol levels in six districts of the Czech Republic, to assess whether the reduction of mean values of total cholesterol recorded during the period between 1985 and 1992 was convincing and to discuss possible causes and consequences of this development. METHODS AND RESULTS: Three cross-sectional surveys of risk factors were implemented in independent random 1% samples of the population aged 25-64 years. In 1985 1256 men (respondence rate 81.5%) and 1317 women (85%) were examined, In 1988 1357 men (85.2%) and 1412 women (88.4%), in 1992 1142 men (73.2%) and 1211 women (76.7%). A detailed check of the deviations in estimations during different time intervals from reference values provided evidence that the analytical method did not have an impact on the revealed changes. In men the mean total cholesterol level was 6.21 (95% confidence limit 6.14-6.28 mmol/l in 1985; 6.29 (6.23-6.35) mmol/l in 1988; 5.99 (5.91-6.06) mmol/l in 1992. In women the mean value of the total cholesterol level was 6.19 (6.12-6.25) mmol/l in 1985; 6.23 (6.17-6.30) mmol/l in 1988; 5.95 (5.88-6.02) mmol/l in 1992. According to variance analysis (ANOVA) the serum cholesterol in 1992 was lower by 0.22 mmol/l (p < 0.0001) than in 1985 and by 0.28 mmol/l (p < 0.0001) lower than in 1988. The drop of cholesterol between 1988-1992 may have been caused by dietary changes recorded in the population. According to nationwide data after 1990 there was a marked drop of the consumption of meat and meat products, milk and dairy products and animal fats, while the consumption of vegetable fats increased. Despite these dietary improvements, in six districts in 1992 fats accounted for 37% of the energy intake, the P/S ratio was only 0.41 in men and 0.46 in women. In these districts in 1992 and 1993 a decline of the standardized mortality rate from IHD in men was recorded. CONCLUSIONS: During an eight-year period the mean serum cholesterol level of men and women decreased significantly in six districts of the Czech Republic. This change was probably associated with a restricted intake of foods which have an impact on the serum cholesterol level.

Development of the cardiovascular risk in the population of the Czech Republic.

Population surveys of the major cardiovascular risk factors were conducted in six districts of the Czech Republic in 1988 and 1992 as part of the WHO MONICA Project. One-percent independent random samples of the population aged 25-64 years were examined and investigated; in 1988, the survey included 1357 men and 1412 women (response rates of 85.5% and 88.4%, respectively); 1139 men and 1214 women with the response rate 71.2% and 75.0%, respectively, were enrolled in 1992. Over the four years, the mean levels of diastolic blood pressure rose from 83.8 mmHg to 85.5 mmHg (p < 0.001) in men; the rise in women from 80.7 mmHg to 81.6 mmHg was non-significant. Systolic blood pressure between the two surveys did not differ significantly. Mean total cholesterol levels declined from 6.24 mmol/l to 5.91 mmol/l (p < 0.001) in men and from 6.16 mmol/l to 5.87 mmol/l (p < 0.001) in women. Mean BMI decreased from 27.5 to 26.9 (p < 0.001) in men and from 27.4 to 26.5 (p < 0.001) in women. The authors assume that the significant decreases in cholesterolaemia and BMI may be caused by changes in the dietary pattern resulting from the market economy principles setting in after the 1989 revolution, and by an increased attention of the population to their health in the new socioeconomic conditions. If the trend continues, one might expect a decrease in mortality from IHD. On the other hand, the rise in diastolic blood pressure may be due to deteriorated control of hypertension.

The effect of body fat distribution on cardiovascular risk factors in the population of the Czech Republic.

A study of cardiovascular risk factors including anthropometry was performed as part of the MONICA project in 1988 in the population of six districts of the Czech Republic. In addition to probands' weight and height, the circumferences of waist and hips were measured to calculate the index of body fat distribution given as WHR (wast/hip ratio). In the age group of 25-64 years, WHR was significantly higher in men (0.936) than in women (0.836 - p < 0.001); in either sex, its value rose with increasing age. WHR values were statistically significantly higher in this group than those found in a Finnish population where males aged 25-64 years had a mean WHR value of 0.90 (p < 0.001), and women of the same age group had a mean WHR of 0.78 (p < 0.001). An analysis of the relationship between abdominal obesity and some cardiovascular risk factors revealed significant correlations between WHR and total cholesterol (men: r = 0.112, p < 0.001; women: r = 0.122, p < 0.001), HDL cholesterol (men: r = -0.184, p < 0.001; women = -0.23, p < 0.001); atherogenic index, i.e., total cholesterol/HDL cholesterol (men: r = 0.183, p < 0.001; women: r = 0.345, p < 0.001), systolic blood pressure (men: r = 0.295, p < 0.001; women: r = 0.263, p < 0.001), diastolic blood pressure (men: r = 0.32, p < 0.001; women: r = 0.237, p < 0.001). The closest correlation was demonstrated between WHR and BMI (men: r = 0.525, p < 0.001; women r = 0.345, p < 0.001). The authors believe WHR is an important parameter for cardiovascular risk assessment and should be determined on a routine basis. The frequent prevalence of abdominal obesity, as suggested by the high values of WHR, contributes to the high cardiovascular risk of the population of the Czech Republic.

Cardiovascular risk factors in the Czech population.

In 1985 and 1988 as part of the WHO's MONICA project two surveys of cardiovascular risk factors were conducted in the population aged 25 to 64 years and resident in the six districts of the Czech Republic collaborating in MONICA. Over a period of three years, the prevalence of smoking decreased from 46% to 41.8% (p less than 0.05) in men. Daily cigarette consumption declined from 17.9 to 15.1 (p less than 0.001) in men and from 11.1 to 10.1 (p less than 0.05) in women. Despite the unchanged prevalence of hypertension during the three years' period the proportion of population with elevated BP levels declined from 22.25% to 19.1% in men (p less than 0.05), and from 16.8% to 14.0% (p less than 0.05) in women as a result of better hypertension control. The prevalence of obesity in men rose from 18.5% to 23.9% (p less than 0.001). The proportion of individuals with a total cholesterol level over 5.2 mmol/l rose from 78.0% to 83.1% (p less than 0.001) in men and from 75.9% to 80.6% in women (p less than 0.01). The changes were favourable only in those risk factors that were actively influenced by the preventive programmes "A Chance for Three Million" in smoking habits, and the "National Programme of Hypertension Control". The authors believe that consistent nationwide preventive programmes might exert a beneficial effect on the profile of risk factors of the whole Czech population.

[The development of cholesterolemia in the Czech population 1985-1988]. / Vývoj cholesterolémie v populaci CR v období let 1985-1988.

The authors followed up the development of serum cholesterol levels in the population aged 25-64 years in six districts of the CR. These districts collaborate since 1984 in the international WHO programme, MONICA. The mean total cholesterol levels increased during 1985-1988 in men from 6.21 mmol/l to 6.28 mmol/l (ns), in women from 6.18 mmol/l to 6.22 mmol/l (ns). During the same period in the population of the six districts the number of subjects with total cholesterol values of 5.2 mmol/l or less declined from 21.9% to 16.8% (p less than 0.001) in men and from 24.0% to 19.4% in women (p less than 0.01). It is important that the greatest change was recorded in the age group of 25-34 years--in men from 38.7% to 27.7% (p less than 0.01) and in women from 46.6% to 36.7% (p less than 0.05). In the investigated population in 1988 cholesterol levels of 6.5 mmol/l and more were recorded in 39.4% of the men and 36.9% of the women, values of 7.8 mmol/l and more in 10% of the men and 9.6% of the women. If in our population, within the framework of prevention of IHD, recommendations of the European Society for Atherosclerosis will be applied, preventive provisions will be necessary in more than 80% of the adult population.

Coronary events in the population of six districts of the Czech Socialist Republic.

In 1984, 640 coronary events were registered in six districts of the Czech Socialist Republic in a population of 164, 185 men aged 25 to 64 years; in a population of 166, 651 women of the same age-group there occurred 162 coronary events. 695 coronary events were according to criteria of the MONICA project (Monitoring of Cardiovascular Diseases and their Risk Factors) confirmed as definite or possible myocardial infarction (MI). The incidence of MI per 100,000 inhabitants amounted in 1984 to 347.7 in men and to 74.4 in women aged 25 to 64 years. The death-rate up to the 28th day of the disease is in men and women the same: one third of patients with a coronary event die within 4 weeks after the onset of symptoms. Death occurs in 75.8% of men and in 69.2% of women during the first 24 hours. Of all subjects with fatal MI, 35.4% of men and 56.1% of women died in hospital.

Interrelations between structure and function in the vocal repertoire of Saimiri. Asking the monkeys themselves where to split and where to lump.

The identification of units used in primate vocal behaviour and the isolation of components essential for intraspecific communication (i.e. having a function) from possibly inessential ones (i.e. having no function) is an absolute prerequisite to a successful analysis of primate vocalizations. For most calls special methods are required because neither the essentials of structure nor their relation to function are known, nor the context involved. For calls without any distinct frequency modulation we showed that the animals utter calls containing categorical amplitude changes. The changes within one call are either very small or very large. The positions or the very large amplitude changes within a call depend on the social situation the animals were subjected to and affect the immediately succeeding vocalization of the conspecific. This proves that in vocal communication discrete components are produced (structure) as well as used (function).

Analysis of Israeli children's fears: a comparison of religious and secular communities.

This study examined the community intervention practice of grouping children on the basis of religious attitudes for analysing community fear responses. The study examined the differences of responses between religious and secular school populations to the Israeli Fear Survey Schedule for Children (IFSSC), an adaptation of the Wolpe and Lang (1964) Fear Survey Schedule. 283 children from secular-trend schools in Israel. 18 of the 99 items of the IFSSC (Klingman & Wiesner, 1982) showed significant differences. The study supported the continuation of the community intervention practice of grouping children on the basis of religious attitude for analyzing IFSSC responses. Religious group affiliation was found to be an influential factor in certain fear responses. The findings point to the need for investigating normative differences among subpopulations with FSS-like instruments. Pre-knowledge and the understanding of the fear level in a community is of great value for emergency-oriented consultation during a crisis. When facing an anxiety-producing situation, the focus of primary as well as early secondary prevention is reaching individuals, as well as groups, of high psychological risk (Caplan, 1964; Klingman & Ben-Eli, 1981; Ollendick & Offman, 1982; Poser & Hartmen, 1979; Shippee, Bradford & Gregory, 1982). The utilization of appropriate classification variables enhances the ability to assess the quality and the degree of reaction to stress within a community.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship of proximity to tension areas and size of settlement to fear levels of Israeli children.

A children's version of the Israeli Fear Survey Schedule was administered to 171 children in the central region of Israel and to 320 children along the tense Northern border. Proximity to the border and size of settlement were found to be factors in the fear levels observed. Beyond the finding that children closer to tension areas had higher fear levels, those from small settlements had higher fear levels than those from medium or large settlements. It was proposed that the variable of population size be viewed as mediated by a sense of social isolation by the subjects in small towns.

[Effect of dl-alpha-tocopherol on incorporation of selenium in "selenium-indicating" organs and on glutathione peroxidase activity in rat and rabbit erythrocytes following application of therapeutic doses of sodium selenite]. / Einfluss von dl-alpha-Tokopherol auf die Seleneinlagerung in "selenanzeigende" Organe und die Aktivität der Glutathionperoxydase in den Erythrozyten von Kaninchen und Ratten nach der Aplikation von Natriumselenit in therapeutischer Dosis.

An explanation of the functions of both vitamin E and selenium in metabolism and an account of the correlations between them is followed by reference to the results obtained by the authors of this paper from studies into the effects of dl-alpha-tocopherol on selenium levels in the M. longissimus dorsi, blood, and liver as well as on the activity of glutathione-peroxidase (EC 1.11.1.9) in erythrocytes of rabbit and rat, following application of therapeutic doses of selenium (0.5 mg/kg live weight). In both species selenium application increased the glutathione-peroxidase activity in erythrocytes. Vitamin E had no additional effect. Application of selenium was followed by rise in intraorganic selenium concentrations. In rabbit, the effect of vitamin T on intraorganic distribution of selenium caused an increased of the selenium level in the liver, but not in the muscles. No vitamin E effect was recordable in the rat. The findings are discussed, with conclusions being suggested for the treatment of metabolic disorders in the context of selenium and vitamin E and for non-invasive liver therapy.

[Glutathione peroxidase activity in erythrocytes and selenium concentration in blood of untreated and selenium-treated rabbits]. / Aktivität der Glutathionperoxidase in den Erythrozyten und Selenkonzentration im Blut unbehandelter und selensubstituierter Kaninchen.

White New Zealander rabbits were tested for erythrocyte-borne reference values of glutathion peroxidase Px activity, with correlations being established between that activity and selenium content of the blood. The average glutathion peroxidase Px activity in untreated clinically intact rabbits was 11.8 K/g Hb. That value doubled following five selenium applications in therapeutic dosage. The values empirically determined were well adapted to normal distribution. Selenium concentrations recorded from organs of control animals were in fair agreement with values established in earlier studies (Wiesner et al., 1978). The correlation coefficient was r = 0.7117 (n = 44, alpha less than 0.001). The equation of regressive straight line Y oder X (y) was y = -5.3 + 59.94x, and that of X over Y (y) was y = 0,27 + 0,0095y, when Y defined the activity of glutathion peroxidase Px and X the selenium level in the blood.

Facilitating and debilitating test anxiety among college students and volunteers for desensitization workshops.

Administered the Alpert-Haber Achievement Anxiety Test (AAT) to 54 students who expressed interest in participating in a test anxiety desensitization workshop. In addition, 182 students from the general college population were tested. Results indicated that both the debilitating and facilitating (AAT) scales were higher for the self-referred volunteer group. These data indicate that these scales are useful in distinguishing self-referred volunteers for behavior modification workshops from a general college population. In addition, the scales of the AAT were correlated with the number of sessions attended by those students who enrolled in the desensitization groups. Results indicated no relationship between attrition and debilitating anxiety. There was a correlation of r = .318 p less than .15 between facilitating anxiety scores and number of sessions attended. It is suggested that facilitating anxiety can function as a measure of S's ego strength in predicting workshop attendance.