May Measurement Month 2019: an analysis of blood pressure screening results from Hungary.

Cardiovascular diseases are not only the leading causes of mortality in Hungary but also the mortality rate is twice as high as the European Union average, so screening programmes identifying subjects with elevated blood pressure (BP) are of utmost importance. May Measurement Month (MMM) is an annual global initiative that began in 2017 aimed at raising awareness of high BP. Hungary joined the 3rd campaign of MMM in 2019 and an overview of the results are presented in this paper. An opportunistic cross-sectional survey of participants aged ≥18 years was carried out in May 2019. Hypertension was defined as systolic BP ≥140 mmHg and diastolic BP ≥90 mmHg or treatment for hypertension, statistical analysis followed the standard MMM protocol. In Hungary, 55 sites were set up in primary and secondary care facilities, in pharmacies, and in malls across all regions, in both cities and villages. Out of 2766 individuals screened, 1286 participants (46.5%) had hypertension. Out of 1869 participants not on antihypertensive medication, 389 (20.8%) had elevated BP. In the case of treated individuals (n = 897), 420 (46.8%) had uncontrolled hypertension. Almost every 2nd subject of the screened cohort had hypertension (treated and controlled, treated and uncontrolled, or untreated). In the untreated cohort, every 5th subject had elevated BP, whilst among patients on antihypertensive medication, every second had uncontrolled BP. By identifying almost one-third of the whole screened cohort with the possibility of newly diagnosed or uncontrolled hypertension, our results confirm the importance of BP screening campaigns.

Vasopressin and post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with a wide range of behavioral disturbances and serious consequences for both patient and society. One of the main reasons for unsuccessful therapies is insufficient knowledge about its underlying pathomechanism. In the search for centrally signaling molecules that might be relevant to the development of PTSD we focus here on arginine vasopressin (AVP). So far AVP has not been strongly implicated in PTSD, but different lines of evidence suggest a possible impact of its signaling in all clusters of PTSD symptomatology. More specifically, in laboratory rodents, AVP agonists affect behavior in a PTSD-like manner, while significant reduction of AVP signaling in the brain e.g. in AVP-deficient Brattleboro rats, ameliorated defined behavioral parameters that can be linked to PTSD symptoms. Different animal models of PTSD also show alterations in the AVP signaling in distinct brain areas. However, pharmacological treatment targeting central AVP receptors via systemic routes is hampered by possible side effects that are linked to the peripheral action of AVP as a hormone. Indeed, the V1a receptor, the most common receptor subtype in the brain, is implicated in vasoconstriction. Thus, systemic treatment with V1a receptor antagonists would be implicated in hypotonia. This implies that novel treatment concepts are needed to target AVP receptors not only at brain level but also in distinct brain areas, to offer alternative treatments for PTSD.

May Measurement Month 2017: an analysis of blood pressure screening in Hungary-Europe.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. The cardiovascular mortality rate in Hungary is twice as high as the European Union average. In a recent Hungarian screening programme, among those volunteers who claimed to be healthy, BP was above 140/90 mmHg in 24% and 39% in women and men, while the control rate was 45% and 36% in women and men, respectively. May Measurement Month (MMM) is a global initiative by the International Society of Hypertension aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. BP measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. In Hungary, 97 sites were set-up in primary and secondary care facilities, in pharmacies and in malls. All regions, both cities and villages were involved. A total of 3967 individuals were screened. After multiple imputation, 2052 subjects (51.8%) had hypertension. 553 (22.4%) of untreated individuals had hypertension, and 666 (44.5%) of treated individuals had uncontrolled BP. More than 50% of the screened cohort had hypertension (treated and controlled, treated and uncontrolled or untreated). By identifying almost one-third of the screened cohort with the possibility of newly diagnosed or uncontrolled hypertension, the Hungarian part of MMM17 suggest that opportunistic screening can identify significant numbers with raised BP.

[Review of the relation between gut microbiome, metabolic disease and hypertension]. / A bélmikrobiom, a metabolikus betegségek és a hypertonia kapcsolatának irodalmi áttekintése.

Gut flora has personal characteristics for each individual, similar to the fingerprints, consisting of a special mixture of bacterial species living in the intestines, now referred to as the gut microbiome. There is a strong correlation between the loss of microbial diversity and the functional bowel disorders, obesity, type 2 diabetes and cardiovascular disease as well as many autoimmune disorders. With genetic testing of stool diversity of the gut microbiome and exact analysis of the species and phylogenetic classification of the gut flora, the changes of diversity can be identified and the overgrowth of some bacteria can be revealed. In cases with pre- and manifest hypertension, an overgrowth of species from the phylum Firmicutes has been reported along with the relative decline of the phylum Bacteroidetes as opposed with cases of normotension. At the same time, the physiological balance among bacterial families was lost. According to the first studies, there is a correlation between hypertension and the lost balance of the gut microflora, both in animal experiments and in the human clinical setting. This evidence also suggests that targeted dietary alteration of the gut microbiome can be a new innovative approach in the treatment of hypertension. Orv Hetil. 2018; 159(9): 346-351.

[Ophthalmological results in the Hungarian comprehensive health care screening program, 2011-2022]. / Szemészeti eredmények Magyarország átfogó egészségvédelmi szuroprogramjában, 2011­2022.

INTRODUCTION: The World Health Organisation's VISION 2020 and World report on vision programs prioritize blindness prevention and vision rehabilitation development. The ophthalmology program, which is part of Hungary's comprehensive health care screening program, plays an important role in the national implementation of these. OBJECTIVE: Summary of the results of Hungary's comprehensive health care screening program's ophthalmology program, which has been going on for 12 years. METHOD: The ophthalmological data of 168 522 people aged between 12 and 99 years who participated in the national screening program were analyzed in nine categories: the presence of eye disease, the use of glasses, the refractive power of the glasses, refractive errors (myopia, anisometropia), the functional vision questionnaire, dry eye, colour vision, educational and communication activities. RESULTS: 18.1% of the participants reported having an eye disease, which was much more common in women and the elderly. The proportion of people who wore glasses reached 66%, with roughly one-third of them lacking appropriate glass strength. Myopia was the most common (58.7%) in people aged 18 to 35. Anisometropia was found in 6.5% of people. Women were more likely than men to have dry eyes (26.1%). Men had a higher rate of colour vision deficiency (5.7%) than women (0.7%). DISCUSSION: As blindness is 80% preventable, national screening tests and comprehensive educational activities that contribute to the early detection and treatment of eye diseases are important. It is critical to call attention to the significant growth in the prevalence of myopia in young people as well as the urgent need for the effective implementation of preventive measures. The importance of proper glasses must also be brought to the attention of the general population because incorrect glasses cause visual problems. CONCLUSION: The national ophthalmology screening and educational activity should be continued in the future, with the goal of reducing the incidence of eye diseases associated with visual impairment and increasing the proportion of people who wear appropriate glasses. To stop the spread of myopia, a national preventive and treatment program should be launched. Orv Hetil. 2023; 164(7): 253-259.

Uncorrected refractive errors are important causes of avoidable visual impairment in Hungary: re-evaluation of two existing national data sets.

AIM: To review existing data for the prevalence of corrected, uncorrected, and inadequately corrected refractive errors and spectacle wear in Hungary. METHODS: Data from two nationwide cross-sectional studies were analysed. The Rapid Assessment of Avoidable Blindness study collected population-based representative national data on the prevalence of visual impairment due to uncorrected refractive errors and spectacle coverage in 3523 people aged ≥50y (Group I). The Comprehensive Health Test Program of Hungary provided data on the use of spectacles in 80 290 people aged ≥18y (Group II). RESULTS: In Group I, almost half of the survey population showed refractive errors for distant vision, about 10% of which were uncorrected (3.2% of all male participants and 5.0% of females). The distance spectacle coverage was 90.7% (91.9% in males; 90.2% in females). The proportion of inadequate distance spectacles was found to be 33.1%. Uncorrected presbyopia was found in 15.7% of participants. In all age groups (Group II), 65.4% of females and 56.0% of males used distance spectacles, and approximately 28.9% of these spectacles were found to be inappropriate for dioptric power (with 0.5 dioptres or more). The prevalence of inaccurate distance spectacles was significantly higher in older age groups (71y and above) in both sexes. CONCLUSION: According to this population-based data, uncorrected refractive errors are not rare in Hungary. Despite recent national initiatives, further steps are required to reduce uncorrected refractive errors and associated negative effects on vision, such as avoidable visual impairment.

The vasopressin-deficient Brattleboro rat: lessons for the hypothalamo-pituitary-adrenal axis regulation.

Adaptation to stress is indispensable to life and the hypothalamo-pituitary-adrenocortical axis is one of the major components of the adaptation. The hypothalamic component consists of corticotropin-releasing hormone and arginine vasopressin, with a questionable contribution of the latter. Vasopressin was more important in the regulation of the adrenocorticotropin secretion in the perinatal vasopressin-deficient Brattleboro rats than in adulthood, where its role depended on the nature of the stressor encountered. In adults, the vasopressin deficiency did not influence the development of chronic stress response. In the neonatal rats, the role of vasopressin was supported by the inhibitory action of a V1b antagonist and vasopressin antiserum. As the corticosterone response to stress did not follow the adrenocorticotropin levels, we assume the presence of an adrenocorticotropin independent adrenal gland regulation in the neonates. We have shown that the apparent dissociation of the corticosterone and adrenocorticotropin responses is not due to the different time course of the two hormone responses, to different level of the corticosterone binding globulin or to changes in the adrenal gland sensitivity. In vitro experiments point to the contribution of beta-adrenoceptors in the process. It was also confirmed by in vivo tests using the vasopressin-deficient Brattleboro pup as a model organism, where corticosterone levels may rise without adrenocorticotropin level changes. Another important question is the role of adrenocorticotropin beyond the corticosterone secretion regulation, which could be supposed, e.g., in cardiovascular events, immunological processes, and metabolism. We can conclude that Brattleboro rats gave us much information about the stress-axis regulation far beyond the role of vasopressin itself.

Prevalence of refractive errors in Hungary reveals three-fold increase in myopia.

AIM: To examine the prevalence and composition of refractive errors in Hungary. METHODS: Nationwide cross-sectional data collected between 2014 and 2019 were analysed from the Comprehensive Health Screening Program of Hungary, which provided spectacle dioptric power and autorefractometry data for 68 227 people (35 850 women and 32 377 men). Their age distribution, 18-99y, was similar to the national demographic distributions. RESULTS: Of the total population, 16.50% of the refractive errors exhibited hyperopia, 40.05% emmetropia, and 43.45% myopia. Myopia was 3 times more frequent (58.7%) in younger ages (18-35y of age) compared to older age groups (19.4% of those 56-70y of age; P<0.001). High myopia showed a low prevalence (0.21%), and an increase parallel with ageing (r=0.716; P=0.009). CONCLUSION: Myopia is the most frequent refractive error in Hungary. The prevalence of myopia is especially increased, up to 2-3 times, in the younger age groups. Nationwide actions need to be taken to reduce the onset of myopia and its associated consequences.

Therapy and prevention of obesity: nutrition, physical activity and medical treatment / Az elhízás kezelése és megelozése: táplálkozás, testmozgás, orvosi lehetoségek.

Összefoglaló. Az elhízás és következményes megbetegedései fontos népegészségügyi problémát jelentenek hazánkban is. Kezelése komoly szakmai kihívás, ugyanakkor prevenciója eredményesebb lehet. Az elhízott betegekkel leggyakrabban találkozó háziorvosok, más szakorvosok és egészségügyi szakemberek részérol nagy igény van egy viszonylag rövid, áttekintheto, naprakész gyakorlatias útmutatóra. A különbözo orvosszakmai társaságokban tevékenykedo, évtizedes szakmai tapasztalatokkal rendelkezo szerzok összefoglalják tudományosan megalapozott, bizonyítékokon alapuló ismereteiket. Az elhízás kezelését lépcsozetesen célszeru megkezdeni, elotte felmérve a beteg motivációját, általános állapotát, lehetoségeit. A szerzok leírják az energiaszükséglet meghatározásával, az étrenddel és a fizikai aktivitás megtervezésével kapcsolatos alapveto szempontokat. Felsorolják a hazánkban elérheto gyógyszereket és metabolikus sebészeti beavatkozásokat, az életmódi támogatás igényét. Az elhízás megelozésében az élet elso 1000 napjának táplálkozása, a késobbiekben a szüloi minta a meghatározó. Sok kihasználatlan lehetosége van a háziorvosok, a lakóközösségek, az állami szervek koordinált együttmuködésének, helyi kezdeményezéseknek. Az elhízás betegségként való meghatározása egyaránt igényel egészségpolitikai és kormányzati támogatást, az elhízottak ellátására szakosodott multidiszciplináris centrumok számának és kompetenciájának növelését. Orv Hetil. 2021; 162(9): 323-335. Summary. Obesity and related morbidities have a high public health impact in Hungary. The treatment is a challenge, but prevention seems more effective. General practitioners, other specialists and health care professionals who are treating obese persons require short, summarized, updated and practical guideline. Hungarian medical professionals of different scientific societies, having decennial practices, are summarizing their evidence-based knowledge. Obesity management requires step by step approach, evaluating previously the general health condition, motivation and options of the patients. The measurement of energy requirement, planning of diet and physical activities, available surgical methods and medications are described in detail with life style and mental support needed. The most important period in the prevention of obesity is the first 1000 days from conception. Other significant factors are the life style habits of the parents. Proper obesity prevention requires better coordination of primary health care, community and governmental activities. Obesity should be defined as morbidity, therefore stronger governmental support and more health-policy initiatives are needed, beside increasing number and developing of multidisciplinary centres. Orv Hetil. 2021; 162(9): 323-335.

Study on endocronological effects of radon speleotherapy on respiratory diseases.

BACKGROUND: Radon, as a radioactive noble gas of natural origin, is generally present in the atmosphere of caves during the speleotherapeutic treatment of different diseases. However, the role of radon in the therapeutic effect is not fully clarified yet. Endocrine parameter levels may be influenced by radon-like endocrine levels in balneotherapeutic treatments (bath treatment). For this reason changes of these parameters were examined in this study. PATIENTS AND METHOD: A total of 81 speleotherapy patients were involved in the survey. They spent four hours daily in Tapolca Cave, five days a week, for two weeks. In this study, the thyreoiedea stimulating hormone, free triiodine-tironin, free thyroxine, prolactine, cortisol, dehydroepiandrosterone sulphate, adrenocorticotropic hormone, and beta endorphine levels of the body were examined before and after the treatment. RESULTS: After statistical analysis of the data a significant decrease of cortisol levels of patients was found, which was not directly correlated with radon concentration. In the case of thyroid hormones, there were no significantly detectable changes of the hormone levels except for low radon concentration levels a significant decrease in the free thyroxine and the thyreoiedea stimulating hormone level of male patients was observed. CONCLUSION: Speleotherapy has an effect on the level of endocrine hormones; however, no direct correlation with differences in radon level was found. For patients whose endocrine levels fell outside the normal endocrine parameter values, more striking changes in endocrine hormone levels were seen, but changes of these parameters could not be statistically analyzed due to the small number of cases.

[Treatment of hypertension associated with prediabetes]. / A prediabéteszhez társult hypertonia kezelése.

Condition prior to diabetes is designated as prediabetes. The use of this term is recommended if fasting plasma glucose exceeds normal level but does not reach the characteristic result of real diabetes. Prediabetes is often characterized by combination of visceral obesity, glucose and lipid metabolism disorders and changes in blood pressure. Change of life style is more important in the treatment of prediabetes associated hypertension than in other hypertensive diseases. In this case, metabolically neutral antihypertensive medication is the treatment of choice. The growing obesity epidemic underlines the significance of prediabetes associated hypertension in public health. While 25% of the adult population suffering from this kind of hypertensive disease, the optimal solution has to be found together with patients, physicians and the money lenders of the social security system.

Evaluation of Meditech ABPM-06 ambulatory blood pressure measuring device, according to the European Society of Hypertension, the British Hypertension Society and the International Organization for Standardization Protocol.

OBJECTIVE: The devices to be used in clinical practice should be tested for accuracy and should be validated through the validation protocol. The aim of this study was to determine the accuracy of the Meditech-ABPM-06 ambulatory blood pressure monitor. MATERIALS AND METHODS: The test was carried out in accordance with the protocol established by the European Society of Hypertension (ESH-IP), the British Hypertension Society, and the ANSI/AAMI/ISO 81060-2-2013 protocols. RESULTS: In the European Society of Hypertension validation procedure the subjects with two or three of the absolute differences between observer and device SBP/DBP measurements within 5 mmHg were 31/31. The average device-observer difference was -0.4 ± 3.9 mmHg for SBP and -0.4 ± 2.8 mmHg for DBP. In the British Hypertension Society validation procedure the mean differences of the test device and observer readings were -1.0 ± 4.6 (systolic) and -1.1 ± 4.5 (diastolic). In the ANSI/AAMI/ISO 81060-2-2013 validation procedure (criterion 1) the mean ± SD of the differences between the test device and reference BP was -0.5 ± 4.0/-0.3 ± 4.5 mmHg (systolic/diastolic). The two criteria of the ANSI/AAMI/ISO were fulfilled. CONCLUSION: The Meditech ABPM-06 blood pressure measure device met the requirements specified by the British Hypertension Society, the European Society of Hypertension International Protocol and the AAMI, and therefore was considered acceptable to clinical use with a Grade of A/A.

[The prevalence of smoking and gender differences according to the data of the national health screening program in 2010-2018]. / Nemi különbségek a dohányzás gyakoriságában hazánkban 2010 és 2018 között.

Introduction: The harmful effects represent an important public health problem in tha world. Aim: Our aim is to report and compare the results of screenings performed in Hungary's Comprehensive Health Screening Program 2010-2020-2030 (MÁESZ) with international data. Method: During the 9-year continuous screening, we analyzed the data of 71 922 women and 60 934 men in the 18-80-year-old population and examined the occurrence of regular daily smokers. Data were collected with the help of special screening data sheets. Results: 24.4% of males and 24.2% of females smoked regularly during the 9-year screening period. Between 2012 and 2015, smoking prevalence showed a temporary significant decline, then, from 2016, it started to increase again. The downturn coincided with the opening of national tobacco stores. In men, the proportion of smokers was significantly higher in young adults (18-25 years) than in women. Later in life, the difference leveled off and even between 46-55 years, the prevalence of smoking was greater in women. There is a difference in smoking patterns between the two genders, which is probably related to marriage and motherhood in women. After 56 years, the proportion of smokers in both genders decreased rapidly. The prevalence of smoking in Hungary in all age groups significantly exceeds the European and world average. Transient increases in middle-aged women have also been reported in European surveys. Conclusion: Compared to 2010, the proportion of smokers has decreased in Hungary, but a new surge observed after 2015 is not a positive phenomenon. We find the high proportion of smoking women worrying. Orv Hetil. 2019; 160(52): 2047-2053.

Control of the hypothalamo-pituitary-adrenal axis in the neonatal period: adrenocorticotropin and corticosterone stress responses dissociate in vasopressin-deficient brattleboro rats.

In adulthood the hypothalamo-pituitary-adrenal axis is controlled by both CRH and arginine vasopressin (AVP). However, in neonates CRH secretion is very low, whereas AVP secretion is fully functional. This suggests that the role of AVP is more pronounced in young than in adult rats. We investigated the role of AVP by studying stress responses in 5, 10, and 20-d-old AVP-deficient Brattleboro rats. Two different stressors were applied: 24-h maternal separation and Hypnorm Grove Oxford UK injections. In heterozygous controls (that do express AVP), both stressors increased plasma ACTH and corticosterone. The ACTH stress response disappeared in AVP-deficient rats, demonstrating that during the perinatal period, the secretion of this hormone is controlled by AVP. Surprisingly, corticosterone responses remained intact in AVP-deficient rats. Similar findings were obtained after 1-, 4-, 12-, and 24-h long maternal separations. Thus, preserved corticosterone stress responses were not explained by changes in the timing of ACTH secretion. In vitro experiments suggested that the dissociation of ACTH and corticosterone stress responses can only be partly explained by higher ACTH responsiveness of the adrenal cortex in AVP-deficient rats. Together, our results show that in neonatal periods, AVP is crucial for the expression of ACTH stress responses, but neither AVP nor ACTH is necessary for the induction of corticosterone stress responses. Discrepant ACTH and corticosterone stress responses may reflect compensatory mechanisms activated by AVP deficiency, but disparate findings suggest that they rather depict a neonate-specific mechanism of hypothalamo-pituitary-adrenal-axis control.

Lasting changes in social behavior and amygdala function following traumatic experience induced by a single series of foot-shocks.

Neuronal plasticity within the amygdala mediates many behavioral effects of traumatic experience, and this brain region also controls various aspects of social behavior. However, the specific involvement of the amygdala in trauma-induced social deficits has never been systematically investigated. We exposed rats to a single series of electric foot-shocks--a frequently used model of trauma--and studied their behavior in the social avoidance and psychosocial stimulation tests (non-contact versions of the social interaction test) at different time intervals. Social interaction-induced neuronal activation patterns were studied in the prefrontal cortex (orbitofrontal and medial), amygdala (central, medial, and basolateral), dorsal raphe and locus coeruleus. Shock exposure markedly inhibited social behavior in both tests. The effect lasted at least 4 weeks, and amplified over time. As shown by c-Fos immunocytochemistry, social interactions activated all the investigated brain areas. Traumatic experience exacerbated this activation in the central and basolateral amygdala, but not in other regions. The tight correlation between the social deficit and amygdala activation patterns suggest that the two phenomena were associated. A real-time PCR study showed that CRF mRNA expression in the amygdala was temporarily reduced 14, but not 1 and 28 days after shock exposure. In contrast, amygdalar NK1 receptor mRNA expression increased throughout. Thus, the trauma-induced social deficits appear to be associated with, and possibly caused by, plastic changes in fear-related amygdala subdivisions.

Detection of a novel immunoreactive endomorphin 2-like peptide in rat brain extracts.

To pursue further the possible de novo biosynthetic pathway of endomorphins in rat brain we raised antibodies to endomorphin-2 conjugate in rabbits. Antiserum R1 recognized endomorphin-2 with good selectivity as compared to endomorphin-1 with a median detection value of 65.5+/-7.5 pg/tube (n=7), whereas R4 antiserum recognized both endomorphins with similar sensitivity. Neither antisera recognized YP-related di- or tripeptides or YGGF-related opioid sequences (enkephalins, beta-endorphin, dynorphin). Using the same rat brain extraction-RP-HPLC-gradient separation paradigm as previously, antisera detected 144.6+/-40.0 (n=3) pg/g wet brain weight endomorphin-2-like immunoreactivity in the fraction corresponding to standard endomorphin-2 retention time and also in the fraction matching endomorphin-2-OH standard retention time (179.1+/-30.1 pg/g). Since R1 failed to recognize authentic endomorphin-2-OH, the second immunoreactive species must be different from both endomorphin-2 and endomorphin-2-OH. Possible biosynthetic intermediates to endomorphins, synthetic YPFFG and YPWFG had retention times close to the parent endomorphin standards in RP-HPLC gradient separation profile. The former was a mu-opioid receptor agonist of medium potency in the in vitro assays (rat brain RBA>P gamma S binding and mouse vas deferens), whereas the latter was a weak mu-opioid receptor agonist with a significant delta-opioid receptorial action as well and a definite indication of partial agonism.

The role of vasopressin in chronic stress studied in a chronic mild stress model of depression.

BACKGROUND AND PURPOSE: Vasopressin plays an important role in the hypothalamo-pituitary-adrenal axis regulation as well as in stress-related disorders. A common view suggested that the role of vasopressin is especially important during chronic stresses. Here we tested the hypothesis that vasopressin-deficient rats may be more resistant to the development of chronic hypothalamo-pituitary-adrenal axis hyperactivity after chronic mild stress. METHODS: Male vasopressin deficient Brattleboro rats were compared to their heterozygous litter mates. Chronic mild stress consisted of different mild stimuli (e.g. wet cages, restraint) for 6 week. The corticosterone changes were followed by repeated tail cutting and organs and blood were collected from decapitated rats. RESULTS: In controls, chronic mild stress resulted in symptoms of chronic stress state characterized by typical somatic (body weight reduction, thymus involution) and endocrine changes (resting plasma ACTH and corticosterone elevation and POMC mRNA elevation in anterior lobe of the pituitary). Unexpectedly, the lack of vasopressin could not influence any chronic mild stress-induced changes. CONCLUSION: Somatic changes and endocrine effects of chronic mild stress are similar in control and vasopressin deficient animals. This suggests that either vasopressin is not indispensable for activating the hypothalamo-pituitary-adrenal axis by chronic stress or the absence of vasopressin is compensated by other mediators (e.g. CRH) in Brattleboro rats.

Median raphe region stimulation alone generates remote, but not recent fear memory traces.

The median raphe region (MRR) is believed to control the fear circuitry indirectly, by influencing the encoding and retrieval of fear memories by amygdala, hippocampus and prefrontal cortex. Here we show that in addition to this established role, MRR stimulation may alone elicit the emergence of remote but not recent fear memories. We substituted electric shocks with optic stimulation of MRR in C57BL/6N male mice in an optogenetic conditioning paradigm and found that stimulations produced agitation, but not fear, during the conditioning trial. Contextual fear, reflected by freezing was not present the next day, but appeared after a 7 days incubation. The optogenetic silencing of MRR during electric shocks ameliorated conditioned fear also seven, but not one day after conditioning. The optogenetic stimulation patterns (50Hz theta burst and 20Hz) used in our tests elicited serotonin release in vitro and lead to activation primarily in the periaqueductal gray examined by c-Fos immunohistochemistry. Earlier studies demonstrated that fear can be induced acutely by stimulation of several subcortical centers, which, however, do not generate persistent fear memories. Here we show that the MRR also elicits fear, but this develops slowly over time, likely by plastic changes induced by the area and its connections. These findings assign a specific role to the MRR in fear learning. Particularly, we suggest that this area is responsible for the durable sensitization of fear circuits towards aversive contexts, and by this, it contributes to the persistence of fear memories. This suggests the existence a bottom-up control of fear circuits by the MRR, which complements the top-down control exerted by the medial prefrontal cortex.

[ACE-inhibitors in renal protection]. / Angiotenzinkonvertáló enzim-gáitlók a vesevédelemben.

The renal impairment due to hypertension causes the disturbance of the renin-angiotensin-aldosterone system which is accompanied with increased activity of the sympathetic nervous system. Administration of angiotensin-converting enzyme inhibitors decreases the production of angiotensin II, secretion of aldosterone, sodium and water retention and peripheral vascular resistance which altogether lead to the reduction of blood pressure. The nephro-protective efficacy of angiotensin-converting enzyme inhibitors was also proved by plenty of extensive international trials both in diabetic and non-diabetic patients with renal diseases. On evidence based medicine we may consider angiotensin-converting enzyme inhibitors and angiotensin receptor blockers--provided there are no contraindications as the standard therapy in all hypertensive and renal diseases.

The effects anandamide signaling in the prelimbic cortex and basolateral amygdala on coping with environmental stimuli in rats.

RATIONALE: Several lines of recent evidence suggest that endocannabinoids affect behavior by influencing the general patterns of challenge responding. OBJECTIVES: Here, we investigated the brain mechanisms underlying this phenomenon in rats. METHODS: The anandamide hydrolysis inhibitor URB597 was condensed into the tip of stainless steel cannulae, which were chronically implanted slightly above the prelimbic cortex (PRL) or the basolateral amygdala (BLA), two important regions of coping and endocannabinoid action. Thereafter, we investigated behavioral responsiveness to ambient light level in the elevated plus-maze and conditioned fear tests. RESULTS: URB597 concentration was ~30 µg/mg protein in target areas; local brain anandamide levels increased threefold, without significant changes in 2-arachidonoylglycerol. High levels of illumination halved the time spent by controls in the open arms of the plus-maze. No similar decrease was observed in rats with URB597 implants in the PRL. High light decreased conditioned fear by 30 % in controls, but not in rats with prelimbic URB597 implants. Unresponsiveness to environmental challenges was not attributable to the anxiolytic effects of anandamide enhancement, as implants induced paradoxical anxiogenic-like effects under low light, which could be explained by effects on stimulus responsiveness rather than by effects on anxiety. URB597 implants targeting the BLA did not affect stimulus responsiveness. CONCLUSIONS: Our findings show that elevated prelimbic anandamide signaling leads to less environment-dependent (more autonomous) behavioral responses to challenges, which is an attribute of active coping styles. These findings are discussed in light of two emerging concepts of endocannabinoid roles, particularly "emotional homeostasis" and "active coping."