Pemphigus vulgaris ehk harilik villtõbi – interdistsiplinaarne haigus

Pemphigus vulgaris on harva esinev raskekujuline autoimmuunne villiline haigus. Haigust põhjustavad autoantikehad, mis tekivad naha basaalmembraani normaalsete komponentide desmogleiin 1 ja 3 vastu, mistõttu epidermises katkevad keratinotsüütidevahelised seosed ning tagajärjeks on laiaulatuslike villide ja erosioonide teke limaskestadel ja nahal (1). Pemphigus vulgaris võib esineda igas vanuses inimestel, kuid sagedamini kesk- ja vanemaealistel patsientidel. Diagnoosi kuldstandardiks on nahabiopsia ning diagnoos kinnitatakse otsese ja/või kaudse immunofluorestsentsmeetodiga (2). Ravimata juhtudel on tegemist eluohtliku haigusega, mille suremus on ka tänapäeval umbes 5–15%. Enne glükokortikosteroidide kasutusele võtmist 1950. aastatel oli selle haiguse suremus üle 75% (3). Farmakoteraapia eesmärgiks on vähendada põletikureaktsiooni ning autoantikehade teket. Raviks kasutatakse kortikosteroidhormoone ja immunosupresseerivaid ravimeid. Varane diagnoos ja õige ravi kiire alustamine parandab prognoosi ning vähendab suremust. Pikaajalise remissiooni saavutamiseks on vajalik regulaarne järelkontroll ning adekvaatne säilitusravi (4–6).Eesti Arst 2014; 93(2):95–9

Optimising and enhancing human performance through nutrition

1 Introduction 545 2 Eating to optimise training 545 2.1 Energy needs for training and the ideal physique 545 2.2 Strategies to reduce mass and body fat 547 2.3 Requirements for growth and gaining lean body mass 548 3 Protein needs for muscle gain, training enhancement and repair 549 4 Fuel needs for training and recovery 550 5 Eating to minimise illness and injury 551 5.1 Calcium, bones and the female athlete triad 551 5.2 Iron depletion 552 5.3 Nutrition for the immune system 553 5.4 Vitamins, minerals and the antioxidant system 553 6 Eating for competition performance 554 6.1 Making weight to meet competition weight targets 554 6.2 Fuelling for competition 554 6.3 Fat adaptation and glycogen restoration strategies 555 6.4 Pre-event eating (1–4 h) 557 6.5 Fuelling during events 558 6.6 Postevent recovery 558 7 Conclusion 559 References 55

Eesti Unemeditsiini Selts Põhjamaade unemeditsiinikonverentsil

Eesti Arst 2019; 98(7):412–41

Photosynthetic Capacity and Water Use Efficiency Depending on Taphrina Fungi Infection in Betula pendula

Käesoleva bakalaureusetöö eesmärgiks oli uurida tuulepesasid põhjustava Taphrina perekonna seene mõju arukaskedele (Betula pendula). Kuna kliima on muutumas aina soojemaks ja niiskemaks ning selline keskkond on soodne seenhaigustele, siis on oluline uurida nende mõju peremeestaimedele. Antud patogeeni mõju arukase füsioloogiale ja anatoomiale uuritakse Eestis esimest korda ning seega on tegemist uute ja oluliste teadmistega seenhaiguste mõju kohta. Töös kasutatud tuulepesad saadi 2015. aasta suvel Tartust ning seejärel teostati gaasivahetuse mõõtmised nii tuulepesadel kui ka kontrollvariantidel. Mõõdeti fotosünteesi kiirust (An) ja õhulõhede juhtivust (gs) ning nende põhjal arvutati ka vee kasutamise efektiivsus (WUE). Lisaks mõõdeti nii lehe- kui ka mesofülli paksust ning määrati klorofülli sisaldused. Tulemusteks saadi, et seenega nakatunud võrsete lehtedes oli fotosünteesi kiirus 3,78µmol m-2 s -1 ja kontrollvõrsete lehtedes keskmiselt 6,51µmol m-2 s -1 . Kuna mesofülli paksus ja klorofülli sisaldus on tuulepesa lehtedes statistiliselt olulisel määral väiksem, siis sellest võib järeldada, et tuulepesaga nakatunud võrsetel on lehtede struktuur muutunud ja seetõttu on ka nende fotosüntees oluliselt vähenenud. Sama puu teistel võrsetel aga on fotosüntees häirimata arvestades, et fotosünteesi väärtused sarnanevad normaalsete kaskedega tehtud uurimuste tulemustele (Kubiske, Pregitzer, 1996). Nakatumata võrsete vee kasutamise efektiivsus antud katses oli keskmiselt 107,71µmol/mol. Kellomäki ja Wang (2001) on katses kasega leidnud kontrolltaime vee kasutamise efektiivsuseks 121µmol/mol. Kuna tuulepesalehtede vee kasutamise efektiivsus on keskmiselt 66,97µmol/mol, siis võib järeldada, et Taphrina seen mõjutab kaskede vee kasutust negatiivselt.The aim of current Bachelor’s thesis was to study the impact of fungi Taphrina that causes witches’ brooms in silver birch (Betula pendula). Future climate conditions in Estonia are increasingly favourable for the spread of fungal diseases as the temperature and precipitation are both predicted to rise. Therefore, it is important to analyse the impact of the possible threats beforehand. While this topic is researched for the first time in Estonia, this knowledge on the impact of Taphrina infection on silver birch physiology and anatomy is new. Witches’ brooms were collected in summer 2015 from Tartu. Then gas exchange measurements with infected and control leaves were carried out. The photosynthetic capacity (An) and stomatal conductance (gs) were measured and based on these the water use efficiency (WUE) was calculated. In addition, leaf and mesophyll thickness was measured on microscopy photos. Also chlorophyll content of leaves was measured. Current study shows that photosynthetic capacity in infected and normal leaves was significantly different. Mean rate of photosynthesis in control leaves was 6.51µmol m-2 s -1 and in infected leaves 3.78µmol m-2 s -1 . Control results are similar to earlier results on shade leaves (Kubiske, Pregitzer, 1996). Furthermore, leaf mesophyll thickness and chlorophyll content were also significantly smaller. Therefore, the decreased photosynthetic capacity of infected leaves’ is mainly caused by changes in leaf structure. The mean water use efficiency in uninfected leaves is 107.71µmol/mol. Kellomäki and Wang (2001) have previously reporter 121µmol/mol for silver birch. The infected leaves’ mean water use efficiency is 66.97µmol/mol, which implies to reduced water use efficiency due to Taphrina infection in birch

Enhanced Fatty Acid Oxidation and FATP4 Protein Expression after Endurance Exercise Training in Human Skeletal Muscle

FATP1 and FATP4 appear to be important for the cellular uptake and handling of long chain fatty acids (LCFA). These findings were obtained from loss- or gain of function models. However, reports on FATP1 and FATP4 in human skeletal muscle are limited. Aerobic training enhances lipid oxidation; however, it is not known whether this involves up-regulation of FATP1 and FATP4 protein. Therefore, the aim of this project was to investigate FATP1 and FATP4 protein expression in the vastus lateralis muscle from healthy human individuals and to what extent FATP1 and FATP4 protein expression were affected by an increased fuel demand induced by exercise training. Eight young healthy males were recruited to the study. All subjects were non smokers and did not participate in regular physical activity (<1 time per week for the past 6 months, VO2peak 3.4±0.1 l O2 min−1). Subjects underwent an 8 week supervised aerobic training program. Training induced an increase in VO2peak from 3.4±0.1 to 3.9±0.1 l min−1 and citrate synthase activity was increased from 53.7±2.5 to 80.8±3.7 µmol g−1 min−1. The protein content of FATP4 was increased by 33%, whereas FATP1 protein content was reduced by 20%. Interestingly, at the end of the training intervention a significant association (r2 = 0.74) between the observed increase in skeletal muscle FATP4 protein expression and lipid oxidation during a 120 min endurance exercise test was observed. In conclusion, based on the present findings it is suggested that FATP1 and FATP4 proteins perform different functional roles in handling LCFA in skeletal muscle with FATP4 apparently more important as a lipid transport protein directing lipids for lipid oxidation

Eesti Unemeditsiini Selts Põhjamaade unemeditsiinikonverentsil

Eesti Arst 2019; 98(7):412–41

Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates

Objective: Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake. Methods: A diet enriched in carbohydrates (80 E% carbohydrate; CHO) and a eucaloric control diet (CON) were provided to nine healthy men for three days. The energy intake during the CHO diet was increased (+75% energy) to ensure similar dietary protein intake in CHO and CON. To control for the effect of caloric surplus, we similarly overfed (+75% energy) the same subjects for three days with a fat-rich diet (78 E% fat; FAT), consisting of primarily unsaturated fatty acids. The three diets were provided in random order. Results: After CHO, plasma FGF21 concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml−1, p < 0.05). In contrast, after FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p < 0.01) with increased leg glucose uptake (62%, p < 0.05) and increased hepatic glucose production (17%, p < 0.01), indicating increased glucose turnover. Plasma fatty acid (FA) concentration was decreased by 68% (p < 0.01), supported by reduced subcutaneous adipose tissue HSL Ser660 phosphorylation (p < 0.01) and perilipin 1 protein content (p < 0.01), pointing to a suppression of adipose tissue lipolysis. Concomitantly, a 146% increase in the plasma marker of hepatic de novo lipogenesis C16:1 n−7 FA (p < 0.01) was observed together with 101% increased plasma TG concentration (p < 0.001) in association with CHO intake and increased plasma FGF21 concentration. Conclusion: Excess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais. Keywords: FGF21, Diet, Carbohydrates, Lipolysis, Live

FFAR4 (GPR120) signaling is not required for anti-inflammatory and insulin-sensitizing effects of omega-3 fatty acids

Free fatty acid receptor-4 (FFAR4), also known as GPR120, has been reported to mediate the beneficial effects of omega-3 polyunsaturated fatty acids (ω3-PUFAs) by inducing an anti-inflammatory immune response. Thus, activation of FFAR4 has been reported to ameliorate chronic low-grade inflammation and insulin resistance accompanying obesity. However, conflicting reports on the role of FFAR4 in mediating the effects of ω3-PUFAs are emerging, suggesting that FFAR4 may not be the sole effector. Hence analyses of the importance of this receptor in relation to other signaling pathways and prominent effects of ω3-PUFAs remain to be elucidated. In the present study, we used Ffar4 knockouts (KO) and heterozygous (HET) mice fed either low fat, low sucrose reference diet; high fat, high sucrose ω3-PUFA; or high fat, high sucrose ω6-PUFA diet for 36 weeks. We demonstrate that both KO and HET mice fed ω3-PUFAs were protected against obesity, hepatic triacylglycerol accumulation, and whole-body insulin resistance. Moreover, ω3-PUFA fed mice had increased circulating protein levels of the anti-inflammatory adipokine, adiponectin, decreased fasting insulin levels, and decreased mRNA expression of several proinflammatory molecules within visceral adipose tissue. In conclusion, we find that FFAR4 signaling is not required for the reported anti-inflammatory and insulin-sensitizing effects mediated by ω3-PUFAs

Exercise Alleviates Lipid-Induced Insulin Resistance in Human Skeletal Muscle–Signaling Interaction at the Level of TBC1 Domain Family Member 4

Excess lipid availability causes insulin resistance. We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline or intralipid infusion. During the last 2 h, a hyperinsulinemic-euglycemic clamp was performed. Femoral catheterization and analysis of biopsy specimens enabled measurements of leg substrate balance and muscle signaling. Each subject underwent two experimental trials, differing only by saline or intralipid infusion. Glucose infusion rate and leg glucose uptake was decreased by intralipid. Insulin-stimulated glucose uptake was higher in the prior exercised leg in the saline and the lipid trials. In the lipid trial, prior exercise normalized insulin-stimulated glucose uptake to the level observed in the resting control leg in the saline trial. Insulin increased phosphorylation of TBC1D1/4. Whereas prior exercise enhanced TBC1D4 phosphorylation on all investigated sites compared with the rested leg, intralipid impaired TBC1D4 S341 phosphorylation compared with the control trial. Intralipid enhanced pyruvate dehydrogenase (PDH) phosphorylation and lactate release. Prior exercise led to higher PDH phosphorylation and activation of glycogen synthase compared with resting control. In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation. The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation