The influence of selenium deficiency and deiodinase inhibitors on innate and adaptive immune responses in juvenile rats

У оквиру ове докторске дисертације испитиван је утицај дефицита селена и инхибитора дејодиназа на урођени и стечени имунски одговор јувенилних пацова. Експеримент је рађен на 128 Wistar пацова мушког пола, подељених у осам експерименталних група: 1. Se+PTU-IA- (контролна група), 2. Se+PTU-IA+, 3. Se+PTU+IA-, 4. Se+PTU+IA+, 5. Se-PTU-IA-, 6. Se-PTU-IA+, 7. Se-PTU+IA- i 8. Se-PTU+IA+. Половини пацова који су формирали селенадекватне групе (Se+) давана је храна са адекватним садржајем селена (0,334 mg/kg). Другој половини пацова који су формирали селендефицитне групе (Se-) давана је храна са ниским садржајем селена (0,031 mg/kg). Као инхибитори дејодиназа примењивани су пропилтиоурацил (PTU+) у дози од 150 mg/L воде за пиће и јопаноична киселина (IA+) у дози од 6 mg/100 g телесне масе. Треће недеље огледа одређивани су статус селена (концентрација селена у пуној крви и активност GPх1 у крви и GPх3 у крвној плазми), статус тиреоидних хормона (концентрација Т3, Т4 и TSH у плазми), способност адхеренце и продукције пероксида перитонеалних макрофага in vitro и титар природних IgМ антитела крвне плазме реактивних са антигенима овчијих еритроцита. Друга половина пацова сваке групе је имунизована у петој и седмој недељи огледа 10%- ном суспензијом овчијих еритроцита. Након седам недеља огледа одређен им је статус селена и хормона тиреоидне осовине, целуларност слезина, релативнa заступљеност (%) и апсолутни број Т и Б лимфоцита и NK ћелија у слезини и титар IgM и IgG антитела реактивних са антигенима овчијих еритроцита. У групама са селендефицитном исхраном потврђен је селендефицитни статус пацова. Примена PTU или комбинације PTU и IA узроковала је системску хипотиреозу, док код пацова третираних јопаноичном киселином није утврђена системска хипотиреоза. Дефицит селена довео је до смањења продукције пероксида од стране перитонеалних макрофага...The effect of selenium deficiency and deiodinase inhibitors on innate and adaptive immune responses in juvenile rats was investigated within this doctoral thesis. The experiment was carried out on 128 male Wistar rats, randomly assigned into 8 experimental groups: Se+PTU-IA- (control group), 2. Se+PTU-IA+, 3. Se+PTU+IA-, 4. Se+PTU+IA+, 5. Se-PTU-IA-, 6. Se-PTU-IA+, 7. Se-PTU+IA- and 8. Se-PTU+IA+. Rats belonging to selenium deficient groups (Se-) were fed with selenium deficient diet (0,031 mg/kg feed). Rats in the other study arm (Se+) were provided with a selenium adequate diet containing 0.334 mg Se/kg feed. Propylthiouracil (PTU+) in a final concentration of 150 mg/L of drinking water, and iopanoic acid (IA+) administered in dose of 6 mg/kg bw, were used as deiodinase inhibitors. Three weeks after the beginning of the experiment the following parameters were determined: selenium status (selenium concentration in full blood; GPx1 activity in blood and GPx3 activity in plasma); thyroid status (T3, T4 and TSH concentration in plasma); rat peritoneal macrophage adherence capacity and peroxide production in vitro and titer of naturally acquired IgM reactive with sheep red blood cells. In the 5th and 7th week of the experiment, the other half of rats in each arm was immunized with 10% suspension of sheep red blood cells. After seven weeks of experiment, selenium and thyroid status of these animals, spleen cellularity, proportion (%) and absolute number of spleen T and B lymphocytes and NK cells, and titers of IgM and IgG antibodies reactive with sheep red blood cells were determined. Selenium deficient status was confirmed in all rats belonging to selenium deficient groups. Treatment with PTU alone or in combination with IA resulted in development of systemic hypothyreosis, while systemic hypothyreosis was not established in rats treated with iopanoic acid. Selenium deficiency resulted in reduction of peroxide production in peritoneal macrophages..

The influence of selenium and deiodinases blockers on juvenile rats body weight

In this work there was investigated the influence of selenium and deodinases blockers on juvenile rats body weight during three months. The experiment was carried out on 64 rats divided into eight groups with eight individual animals per group. Following groups were formed: 1. Se+PTU-IA- (control group), 2. Se+PTU+IA+, 3. Se+PTU+IA-, 4. Se+PTU- IA+, 5. Se-PTU-IA-, 6. Se-PTU+IA+, 7. Se-PTU+IA- and 8. Se-PTU-IA+. The groups labeled (Se+) were selenium adequate and they were fed with food that contained 0.334 mg Se/kg. The groups labeled (Se-) were selenium deficient and obtained food with 0.031 mg Se/kg. As deiodinases blockers there were used propylthiouracil (PTU+) in a dose of 150 mg/L of drinking water and iopanoic acid (IA+) in a dose of 6 mg/100 g TM intraperitoneally. Body weight of experimental rats was measured every seven days. After three weeks of treatment there were taken blood samples of animals from all experimental groups and following parameters were determined: selenium concentration in blood, thyroxine (T4), triiodothyronine (T3) and thyroidstimulating hormone (TSH) in blood plasma. Analysis of the samples showed that the animals from the groups treated with PTU had lower body weight in regard to the control group, as well as lower concentration of T3 and T4 in plasma. Selenium deficient rats had lower average body weight compared to the selenium adequate ones after three weeks, but there were no differences in thyroid hormones concentration. The lowest average body weight was noticed in selenium deficient rats groups treated with PTU. [Projekat Ministartsva nauke Republike Srbije, br. TR31050 i br. TR31003

Deficijencija B12 vitamina kod deteta majke na veganskoj ishrani

Vitamin B12 deficiency usually occurs in exclusively breastfed infants whose mothers have pernicious anaemia or are vegetarian. Early treatment of vitamin B12 deficiency in infants can prevent potentially neurologic sequelae. A male child aged 13 months has been hospitalized due to failure to thrive, feeding problems, pallor, weakness and hypotonia. During the pregnancy mother did not eat meat and during lactation she also excluded eggs and milk. The child was exclusively breastfed. Laboratory investigations showed a haemoglobin level of 3.5 g/dL, haematocrit 10%, red blood cell count of 0.99 × 1012/L, white blood cell count of 4.23 × 109 /L and platelet count of 55 × 109 /L. Vitamin B12 level was low. A bone marrow aspiration finding was consistent with megaloblastic anaemia. The magnetic resonance imaging showed brain atrophy. Vitamin B12 in a dose of 10µg per kg was applied intramuscularly daily for 2 weeks, then once weekly. Three days after initiating B12 vitamin therapy there was an improvement in the blood count with the gradual improvement of neurological state. Vitamin B12 deficiency is a treatable cause of pancytopenia and neurological dysfunction in children and should be considered as differential diagnosis in an infant with neurological symptoms.Deficijencija B12 vitamina se obično javlja kod odojčadi koja su na prirodnoj ishrani a čije majke imaju pernicioznu anemiju ili su vegetarijanci. Pravovremeno lečenje deficijencije B12 vitamina kod odojčadi može da prevenira potencijalne neurološke posledice. Malo muško dete uzrasta 13 meseci je hospitalizovano zbog nenapredovanja, problema sa hranjenjem, bledila, slabosti i hipotonije.Tokom trudnoće majka nije jela meso dok je tokom dojenja iz ishrane isključila i jaja i mleko. Dete je isključivo dojeno. U laboratorijskim nalazima nivo hemoglobina je iznosio 3,5 g/dl, hematokrit 10%, broj eritrocita je bio 0.99×1012/L, broj leukocita 4.23×109 /L i broj trombocita 55×109 /L. Nivo B12 vitamina je bio snižen. Nalaz biopsije kostne srži ukazivao je na megaloblastnu anemiju. Na magnetnoj rezonanci endokranijuma viđena je atrofija mozga. Vitamin B12 u dozi od 10 mikrograma/kg primenjen je intramuskularno svakodnevno tokom 2 nedelje, potom jednom nedeljno.Tri dana od započinjanja terapije zabeleženo je poboljšanje hematoloških vrednosti uz postepeno poboljšanje neurološkog statusa. Deficijencija B12 vitamina je uzrok pancitopenije i neurološke disfuncije kod dece koju je moguće lečiti. Kod odojčeta sa neurološkim simptomima ova deficijencija treba da bude razmotrena kao diferencijalna dijagnoza

Effects of selenium and thyroid hormone deficiency on peritoneal macrophages adhesion and occurrence of natural IGM antibodies in juvenile rats

Both selenium, as an effector and regulator of antioxidative enzymes activity, and thyroid hormones are potent immunomodulators. Besides, selenium incorporated into iodothyronine deiodinases is involved in the thyroid function and thus indirectly regulates the immune response. Studies of the mutual infl uence of selenium and thyroid hormones on the immune response are scarce, hence we analyzed the effects of an iodothyronine deiodinases blocker, propylthiouracil (PTU), and selenium defi ciency on the function of peritoneal macrophages, and titer of naturally occurring anti-sheep red blood cells (SRBC) IgM antibodies in juvenile rats. The experiment was carried out on 64 Wistar male rats allotted to 4 groups: controlselenium adequate PTU-group; selenium adequate, PTU+ group; selenium defi cient, PTU-group; and selenium defi cient, PTU+. The selenium adequate and selenium defi cient groups were fed a diet containing 0.334 and 0.031 mg Se/kg, respectively. PTU+ groups received PTU (150 mg/L) in drinking water. After 3 weeks, thyroxine (T-4), triiodothyronine (T-3), and thyroid stimulating hormone (TSH) were determined. The animals having "intermediate" concentrations of T-3 (1.56-1.69 nmol/L) and T 4 (41-50 nmol/L) were excluded from further analysis. Thus, PTU+ groups included hypothyroid animals (T-3 lt = 1.55 nmol/L; T-4 lt = 40 nmol/L), while PTU-groups included euthyroid rats (T-3 lt = 1.70 nmol/L; T-4 lt = 50 nmol/L). Both groups of selenium defi cient rats had, when compared to the control group, a signifi cantly lower activity of glutathione peroxidase GPx1 and GPx3. Neither selenium defi ciency nor PTU infl uenced the adherence of peritoneal macrophages. Selenium defi ciency signifi cantly decreased the peroxide synthesis in macrophages and signifi cantly increased the titer of anti-SRBC IgM. Hypotyroidism alone or in combination with selenium defi ciency had no infl uence on these parameters

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults.

BACKGROUND: Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults. METHODS: We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5-19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5-19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity). FINDINGS: Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (-0·01 kg/m2 per decade; 95% credible interval -0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m2 per decade (0·69-1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m2 per decade (0·64-1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m2 per decade (-0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m2 per decade (0·50-1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4-1·2) in 1975 to 5·6% (4·8-6·5) in 2016 in girls, and from 0·9% (0·5-1·3) in 1975 to 7·8% (6·7-9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0-12·9) in 1975 to 8·4% (6·8-10·1) in 2016 in girls and from 14·8% (10·4-19·5) in 1975 to 12·4% (10·3-14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7-29·6) among girls and 30·7% (23·5-38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44-117) million girls and 117 (70-178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24-89) million girls and 74 (39-125) million boys worldwide were obese. INTERPRETATION: The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults. FUNDING: Wellcome Trust, AstraZeneca Young Health Programme

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Status and Trends of Physical Activity Surveillance, Policy, and Research in 164 Countries: Findings From the Global Observatory for Physical Activity—GoPA! 2015 and 2020 Surveys

Background: Physical activity (PA) surveillance, policy, and research efforts need to be periodically appraised to gain insight into national and global capacities for PA promotion. The aim of this paper was to assess the status and trends in PA surveillance, policy, and research in 164 countries. Methods: We used data from the Global Observatory for Physical Activity (GoPA!) 2015 and 2020 surveys. Comprehensive searches were performed for each country to determine the level of development of their PA surveillance, policy, and research, and the findings were verified by the GoPA! Country Contacts. Trends were analyzed based on the data available for both survey years. Results: The global 5-year progress in all 3 indicators was modest, with most countries either improving or staying at the same level. PA surveillance, policy, and research improved or remained at a high level in 48.1%, 40.6%, and 42.1% of the countries, respectively. PA surveillance, policy, and research scores decreased or remained at a low level in 8.3%, 15.8%, and 28.6% of the countries, respectively. The highest capacity for PA promotion was found in Europe, the lowest in Africa and low- and lower-middle-income countries. Although a large percentage of the world’s population benefit from at least some PA policy, surveillance, and research efforts in their countries, 49.6 million people are without PA surveillance, 629.4 million people are without PA policy, and 108.7 million live in countries without any PA research output. A total of 6.3 billion people or 88.2% of the world’s population live in countries where PA promotion capacity should be significantly improved. Conclusion: Despite PA is essential for health, there are large inequalities between countries and world regions in their capacity to promote PA. Coordinated efforts are needed to reduce the inequalities and improve the global capacity for PA promotion