Weather Variability and COPD: A Risk Estimation Identified a Vulnerable Sub-population in Hungary.

BACKGROUND/AIM: Chronic obstructive pulmonary disease (COPD) is a major public health concern, affecting over 200 million people worldwide in 2019. The prevalence of COPD has risen by 40% from 1990 to 2010 and continued to increase by 13% from 2010 to 2019, causing over 3 million deaths globally in 2019, ranking it as the third leading cause of death. This study explored how daily weather changes relate to the number of COPD-related emergency department (ED) visits. MATERIALS AND METHODS: We collected data on daily COPD-related ED visits in 2017 in Pécs along with corresponding meteorological data to analyze this connection. RESULTS: High diurnal temperature range (DTR) and day-to-day variability in dew point were linked to a 4.5% increased risk of more COPD-related ED visits. Notably, DTR had a stronger impact on males, contributing to a 6.3% increase, while dew point variability significantly affected males with an odds ratio (OR) of 1.083. (OR=1.083). Stratifying by age revealed heightened risks for those aged 30-39 (43.5% increase) and 50-59 (7.6% increase). Females aged 30-39 and 50-59 faced elevated risks of 42.7% and 9.1%, respectively, whereas males aged 60-69 showed a 9.8% increase. CONCLUSION: Our findings highlight the influence of weather variations on COPD-related ED visits, with nuanced effects based on age and sex.

Resveratrol Improves Heart Function by Moderating Inflammatory Processes in Patients with Systolic Heart Failure.

The effects of resveratrol (RES) in heart failure have already been evaluated in animal models; however, in human clinical trials, they have not been confirmed yet. The aim of this study was to assess the effects of resveratrol treatment in systolic heart failure patients (heart failure with reduced ejection fraction or HFrEF). In this human clinical trial, 60 outpatients with NYHA (New York Heart Association) class II-III HFrEF were enrolled and randomized into two groups: receiving either 100-mg resveratrol daily or placebo for three months. At the beginning and at the end of the study echocardiography, a six-minute walk test, spirometry, quality of life questionnaire, lab test and RNA profile analysis were performed. The systolic and diastolic left ventricular function, as well as the global longitudinal strain, were improved significantly in the resveratrol-treated group (RES). Exercise capacity, ventilation parameters and quality of life also improved significantly in the RES group. In parallel, the cardiac biomarker levels (N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and galectin-3) decreased in the treated group. The level of inflammatory cytokines decreased significantly after RES supplementation, as a consequence of the decreased expression level of leucocyte electron transport chain proteins. The main findings of our trial are that RES treatment added to the standard heart failure therapy improved heart function and the clinical condition by moderating the inflammatory processes in patients with HFrEF.

[Prevalence and severity of chronic parodontitis and oral mucosal lesions in chronic obstructive lung disease]. / A krónikus parodontitis, illetve szájnyálkahártya-laesiók elofordulása és súlyossága krónikus obstruktív tüdobetegségben.

INTRODUCTION: Chronic parodontitis is a prevalent oral disease that may lead to the loss of teeth independently of caries. Some systemic diseases (e.g., diabetes mellitus, chronic renal failure) may aggravate chronic parodontitis. On the other hand, this oral disease may aggravate other systemic diseases. Earlier studies suggested a correlation between chronic parodontitis and very severe chronic obstructive pulmonary disease (COPD). AIM: The aim of our study was the investigation of the correlation between chronic parodontitis and chronic obstructive pulmonary disease. METHOD: We have recruited patients of the Department of Dentistry, Oral and Maxillofacial Surgery, Medical School, University of Pécs, in the study. Volunteers were assigned into a COPD (n = 29) and control group (n = 45). Airflow limitation of the COPD group (FEV1/FVC: 61.52 ± 3.2%) corresponded to GOLD 2 (global initiative for chronic obstructive lung disease; FEV1: 52.66 ± 3.57%). Oral health assessment included mean and maximal clinical attachment loss, mobility of teeth, decayed/filled and missing teeth, Löe-Silness, oral hygiene and bleeding on probing indexes. One-way ANOVA and non-parametric Mann-Whitney tests were used for statistical analysis. RESULTS: Oral health of the COPD group was worse than that of the controls. In this group the mean and maximal clinical attachment loss, mobility of teeth, the Löe-Silness, the oral hygiene and bleeding on probing indexes were higher. CONCLUSIONS: Our results confirm the positive correlation between chronic parodontitis and a moderate level of chronic obstructive pulmonary disease. However, it is not clear whether the COPD-associated systemic inflammation aggravated the oral status or the chronic parodontitis influenced negatively chronic obstructive pulmonary disease. Orv Hetil. 2018; 159(21): 831-836.

Age-related changes in central effects of corticotropin-releasing factor (CRF) suggest a role for this mediator in aging anorexia and cachexia.

Hypothalamic corticotropin-releasing factor (CRF) lays downstream to catabolic melanocortins and at least partly mediates their catabolic effects. Age-related changes in the melanocortin system (weak responsiveness in middle-aged and a strong one in old rats) have been shown to contribute to middle-aged obesity and later to aging anorexia and cachexia of old age groups. We hypothesized that catabolic (anorexigenic and hypermetabolic) CRF effects vary with aging similarly to those of melanocortins. Thus, we aimed to test whether age-related variations of CRF effects may also contribute to middle-aged obesity and aging anorexia leading to weight loss of old age groups. Food intake, body weight, core temperature, heart rate, and activity were recorded in male Wistar rats of young, middle-aged, aging, and old age groups (from 3 to 24 months) during a 7-day intracerebroventricular CRF infusion (0.2 µg/µl/h) in a biotelemetric system. In addition, CRF gene expression was also assessed by quantitative RT-PCR in the paraventricular nucleus (PVN) of intact animals of the same age groups. The infusion suppressed body weight in the young, aging, and old rats, but not in middle-aged animals. Weak anorexigenic and hypermetabolic effects were detected in the young, whereas strong anorexia (without hypermetabolism) developed in the oldest age groups in which post mortem analysis showed also a reduction of retroperitoneal fat mass. CRF gene expression in the PVN increased with aging. Our results support the potential contribution of age-related changes in CRF effects to aging anorexia and cachexia. The role of the peptide in middle-aged obesity cannot be confirmed.

Acute central effects of alarin on the regulation on energy homeostasis.

Hypothalamic neuropeptides influence the main components of energy balance: metabolic rate, food intake, body weight as well as body temperature, by exerting either an overall anabolic or catabolic effect. The contribution of alarin, the most recently discovered member of the galanin peptide family to the regulation of energy metabolism has been suggested. Our aim was to analyze the complex thermoregulatory and food intake-related effects of alarin in rats. Adult male Wistar rats received different doses of alarin (0.3; 1; 3 and 15µg corresponding approximately to 0.1, 0.33, 1, and 5 nmol, respectively) intracerebroventricularly. Regarding thermoregulatory analysis, oxygen consumption (indicating metabolic rate), core temperature and heat loss (assessed by tail skin temperature) were recorded in an Oxymax indirect calorimeter system complemented with thermocouples and Benchtop thermometer. In order to investigate potential prostaglandin-mediated mechanisms of the hyperthermic effect of alarin, effects of intraperitoneally applied non-selective (indomethacin, 2mg/kg) or selective cyclooxygenase inhibitor (COX-2 inhibitor meloxicam, 1; 2mg/kg) were tested. Effects of alarin on daytime and nighttime spontaneous food intake, as well as, 24-h fasting-induced re-feeding were recorded in an automated FeedScale system. Alarin increased oxygen consumption with simultaneous suppression of heat loss leading to a slow coordinated rise in core temperature. Both applied COX-inhibitors suppressed this action. Alarin failed to induce daytime food intake, but suppressed spontaneous nighttime and also fasting-induced re-feeding food intake. Alarin appears to elicit a slow anorexigenic and prostaglandin-mediated, fever-like hyperthermic response in rats. Such a combination would characterize a catabolic mediator. The potential involvement of alarin in sickness behavior may be assumed.

Acute central effects of corticotropin-releasing factor (CRF) on energy balance: Effects of age and gender.

Previously demonstrated age-related changes in the catabolic melanocortin system that may contribute to middle-aged obesity and aging anorexia, raise the question of the potential involvement of corticotropin-releasing factor (CRF) in these phenomena, as this catabolic hypothalamic mediator acts downstream to melanocortins. Catabolic effects of CRF were shown to be mediated by both CRF1 (hypermetabolism) and CRF2 (anorexia) receptors. To test the potential role of CRF in age-related obesity and aging anorexia, we investigated acute central effects of the peptide on energy balance in male and female rats during the course of aging. Effects of an intracerebroventricular CRF injection on food intake (FI), oxygen-consumption (VO2), core- and tail skin temperatures (Tc and Ts) were studied in male and female Wistar rats of five different age-groups (from 3- to 24-month). Anorexigenic responsiveness was tested during 180-min re-feeding (FeedScale) following 24-h fasting. Thermoregulatory analysis was performed by indirect calorimetry (Oxymax) complemented by thermocouples recording Tc and Ts (indicating heat loss). CRF suppressed FI in 3-month male and female animals. In males, CRF-induced anorexia declined with aging, whereas in females it was maintained in all groups. The peptide increased VO2 and Tc in all male age-groups, while the weaker hypermetabolic response characterizing 3-month females declined rapidly with aging. Thus, age-related alterations in acute central anorexigenic and hypermetabolic effects of CRF show different non-parallel patterns in males and females. Our findings underline the importance of gender differences. They also call the attention to the differential age-related changes in the CRF1 and CRF2 receptor systems.

Regulatory Alterations of Energy Homeostasis in Spontaneously Hypertensive Rats (SHR).

Spontaneously hypertensive rats (SHR) have high sympathetic tone and progressive hypertension. Chronic calorie-restriction prevents hypertension. Their food intake (FI) and body weight are lower than in normotensive (NT) controls, even on a high-fat diet, suggesting a dysregulation of energy homeostasis. We assumed enhanced activity of hypothalamic anorexigenic melanocortins and diminished tone of orexigenic neuropeptide Y (NPY) in the background. FI of male SHR and NT Wistar rats was recorded in a FeedScale system upon intracerebroventricular injection of NPY, melanocortin ligands alpha-melanocyte-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP) or during a 7-day intracerebroventricular infusion of melanocortin antagonist HS024. Alpha-MSH, NPY, and AgRP immunoreactivities were semi-quantified in the arcuate (ARC) and paraventricular (PVN) nuclei of the hypothalamus in NT vs. SHR. Proopiomelanocortin gene expression was also assessed by quantitative RT-PCR in the ARC. Melanocortin-induced anorexia was stronger, FI induced by NPY or HS024 was smaller and delayed in SHR. Cellular alpha-MSH-specific signal density was higher in the ARC of SHR as evaluated by immunofluerescence, which was supported by PCR data. In the PVN, no differences in alpha-MSH-, NPY-, or AgRP-immunosignal were observed. Our results suggest that a higher melanocortin production/responsiveness and lower NPY responsiveness may contribute to the body weight dysregulation of SHR.

Leptin and aging: Review and questions with particular emphasis on its role in the central regulation of energy balance.

Leptin is produced mainly in the white adipose tissue and emerged as one of the key catabolic regulators of food intake and energy expenditure. During the course of aging characteristic alterations in body weight and body composition in humans and mammals, i.e. middle-aged obesity and aging anorexia and cachexia, suggest age-related regulatory changes in energy balance in the background. Aging has been associated with increased fat mass, central and peripheral leptin resistance as indicated by its failure to reduce food intake, to increase metabolic rate and thereby to induce weight loss. Leptin resistance is a common feature of aging and obesity (even in the young). The question arises whether aging or fat accumulation plays the primary role in the development of this resistance. The review focuses mainly on mechanisms and development of central leptin resistance. Age-related decline primarily affects the hypermetabolic component of central catabolic leptin actions, while the anorexigenic component is even growing stronger in the late phase of aging. Obesity enhances resistance to leptin at any age, particularly in old rats, calorie-restriction, on the other hand, increases responsiveness to leptin, especially in the oldest age-group. Thus, without obesity, leptin sensitivity appears not to decrease but to increase by old age. Interactions with other substances (e.g. insulin, cholecystokinin, endogenous cannabinoids) and life-style factors (e.g. exercise) in these age-related changes need to be investigated.

Age versus nutritional state in the development of central leptin resistance.

Leptin, a catabolic adiposity signal acts in the hypothalamus via suppressing food intake and inducing hypermetabolism. Age and obesity are accompanied by leptin resistance. The present study aimed to clarify which components of the catabolic leptin effects are influenced most strongly by aging and which ones by nutritional state-induced alterations in body composition. In our biotelemetric study the effects of a 7-day intracerebroventricular leptin infusion on various parameters of energy balance (food intake, body weight, oxygen consumption, heart rate and body temperature) were analyzed in male Wistar rats of different age-groups (from 3 to 24 months) and nutritional states (normally fed, diet-induced obese and calorie-restricted). Leptin resistance of older animals affected hypermetabolic actions, whereas leptin induced anorexia in all age-groups. Weight reducing effect of leptin diminished in middle-aged and aging animals to become significant again in the oldest group. In diet-induced obese rats leptin-induced hypermetabolism of the young rats and hypermetabolism plus anorexia of the aging ones were suppressed. Calorie-restriction reduced body weight and fat mass to a similar extent in all age-groups. It strongly enhanced leptin-induced hypermetabolism at all ages and prevented the manifestation of anorexigenic actions of leptin with the exception of the oldest group. This latter finding suggests an unexpected increase of responsiveness to anorexigenic leptin actions in old rats. Accordingly, anorexia and hypermetabolism change in disparate ways with aging. Nutritional state predominantly influences hypermetabolic leptin actions. Resistance to both hypermetabolic and anorexigenic actions were promoted by obesity, while calorie-restriction enhanced responsiveness to leptin, especially in old rats.

Thermoregulatory effect of alarin, a new member of the galanin peptide family.

In the background of obesity, among other factors, regulatory alterations in energy balance affecting peptide systems may also be assumed. Regulation of energy balance does not only involve maintenance of body weight but also that of metabolic rate and core temperature. The contribution of alarin, a new member of the potentially orexigenic galanin peptide family, to the regulation of energy metabolism has been recently suggested. Our aim was to analyze the thermoregulatory effects of alarin in rats.   Adult male Wistar rats received full-length alarin (alarin 1-25), its truncated form (alarin 6-25Cys) or scrambled alarin in various doses intracerebroventricularly at different ambient temperatures. Oxygen consumption, heat loss (assessed by tail skin temperature) and core temperature of rats were recorded in an indirect calorimeter system. Upon alarin injection at 25 °C, an increase in oxygen consumption and continuous tail skin vasoconstriction induced a slow rise in core temperature that reached 0.5 °C by 120 and 1.0 °C by 180 min. At cooler or slightly warmer temperatures similar responses were seen. Neither the truncated nor the scrambled alarin elicited any significant thermoregulatory response, however, the truncated form antagonized the hyperthermic actions of the full-length peptide. Alarin appears to elicit a slow hypermetabolic, hyperthermic response in rats. Such a thermoregulatory response would characterize a catabolic (anorexic and hypermetabolic) mediator. Further investigations are needed to clarify the complex role of alarin in energy homeostasis.

Complex catabolic effects of central alpha-MSH infusion in rats of altered nutritional states: differences from leptin.

The hypothalamic melanocortin (MC) system is a major catabolic regulator of energy balance: it suppresses food intake (FI), elevates metabolic rate, and reduces body weight (BW). The primary activator of the MC system [mainly via the alpha-melanocyte stimulating hormone (alpha-MSH)] is the adipocyte-derived leptin. With increasing BW, resistance develops to leptin-induced anorexia, but independent of this, in genetically modified animals, some alpha-MSH actions were maintained. We investigated the responsiveness of the MC system in its complexity (FI vs. metabolic correlates) in genetically intact male Wistar rats of different nutritional states (and different leptin sensitivities), i.e., in rats aged 2 months [normally fed (NF2)] or 6 months [calorie-restricted (CR6), fed ad libitum (NF6), and high-fat diet-induced obese (HF6) groups]. A 7-day-long, 1-µg/µl/h intracerebroventricular infusion of alpha-MSH reduced BW in all groups, particularly in NF6 and NF2 animals, and even CR6 rats lost BW upon alpha-MSH infusion (in contrast to leptin administration). Anorexia developed in NF2-NF6 and less in CR6 groups, and some FI fall was also seen in HF6 rats. The hypermetabolic effects (temperature/heart rate elevations) were most pronounced in CR6 and next in HF6 rats. These data suggest that alpha-MSH responsiveness is maintained in various forms (depending on nutritional state), despite obesity-induced leptin resistance.

Anorexic vs. metabolic effects of central leptin infusion in rats of various ages and nutritional states.

Age-related obesity is known to be adjoined by leptin resistance. It has not been clarified whether the resistance is cause or result of obesity. In the present experiments, the anorexic (suppressing food intake and body weight) and hypermetabolic (increasing body temperature (Tc), activity, and heart rate (HR), indicating metabolic rate) responses to 7-day-long intracerebroventricular leptin infusion were compared in 2- and 6-month-old normally fed (NF2 and NF6 groups), 6-month-old high-fat-diet-induced obese (HF6), and 6-month-old calorie-restricted (CR6) rats. The anorexic effects were inversely related to fat content: They were most pronounced in NF2, less in NF6, non-significant in HF6 rats, but also absent in CR6 animals of the lowest fat content. This virtual leptin resistance in CR6 rats was due to their high orexigenic activity (enhanced feeding response to NPY). In contrast, CR6 rats were hypersensitive to the metabolic effects of leptin infusion (rise in Tc and HR; biotelemetric measurements), NF2 were still sensitive, while NF6 and HF6 rats exhibited moderate or low sensitivity. In conclusion, leptin resistance depends on body fat content rather than on age itself, although with age the proportion of fat tissue increases and contributes to self-perpetuating rise in body weight.