The analysis of polymorphism in the genes for the receptors of sex steroids in women with the premature ovarian failure

Prosečna starost za ulazak u menopauzu u populacijama žena zapadnih zemalja je približno 51 godina. Prevremenu disfunkciju ovarijuma (POI) karakteriše amenoreja, hipoestrogenizam i povišeni gonadotropini kod žena mlađih od 40 godina. Uzroci POI su heterogeni, uključujući aberacije X hromozoma, infekcije, jatrogene uzroke (hirurgija, hemoterapija, zračenje) i autoimmune bolesti. Oko 20-30% žena sa POI ima i porodičnu anamnezu, sa ženskim članovima porodice koji nose istu dijagnozu. Stoga je genetska osnova za poremećaj verovatno uzrok ovog kliničkog stanja. Poznato je da normalni razvoj i funkcija jajnika zahtevaju ekspresiju i pravilnu koordinaciju mnogih gena. Navedeni mehanizmi su većinom nepoznati i uprkos genetskim defektima koji su identifikovani u nekoliko gena kandidata, u velikom broju POI slučajeva nije pronađen nijedan uzrok i zato su klasifikovani kao idiopatski POI. S obzirom da su veličina inicijalne folikularne formacije i brzina folikularnog trošenja povezane sa starošću pri menopauzi i s obzirom na činjenicu da ovi zametci ćelija izražavaju gonado steroidne receptore u različitim fazama razvoja, moguće je da genetičke varijante u genima za receptore polnih steroida, koje su uključene u održavanje funkcije jajnika, mogu uticati na rizik od PPOI. Osnovni modulatori folikulogeneze su estrogenski receptori (ERα i ERβ) koji direktno kroz regulisanje hipofiza-gonadne ose omogućavaju delovanje estrogena. Sekventni polimorfizam ERα gena (ESR1:estrogen receptor 1) je pokazao povezanost sa osteoporozom, neobjašnjivom neplodnošću, nižim odgovorom na stimulaciju jajnika, fibromima u materici i endometriozom. Nedavna istraživanja su pokazala da su mikrosatelitni polimorfizmi gena za ESR1 povezani sa PPOI u korejskoj kohorti. Nedostatak estrogena povezan je sa povećanim poremećajem kostiju, ubrzanim gubitkom kostane mase što dovodi do povećane podložnosti osteoporozi i frakturi kostiju. Nasleđivanje koštane mase je pod poligenskom kontrolom. SOHLH1 i SOHLH2 geni su faktori transkripcije vazni za razvoj PPOI. SOHLH2 gen nalazi se na 13 hromozomu, i jedan je od testis-specifičnih faktora koji su od suštinske važnosti za spermatogenezu, ovogenezu i folikulogenezu. SOHLH 1 i 2 geni su izraženi isključivo u primordijalnim folikulima do primarne folikularne faze i predstavljaju master regulatore gena jajne ćelije odgovorne za rani rast i diferencijaciju folikula...The average age for menopause in Western populations is approximately 51 year. Premature ovarian failure (PPOI) is characterised by amenorrhoea, hypoestrogenism and elevated gonadotropins and affects of women under the age of 40. The causes of PPOI are heterogeneous, including chromosome X defects, infections, iatrogenic (surgery, chemotherapy, radiation), and autoimmune disease. Approximately 20-30% of women with PPOI will have other affected female members, hence a genetic basis for the disorder is a likely cause for this clinical scenario. It is known that normal ovarian development and function require the expression and proper coordination of many genes. The underlying mechanisms are largely unknown and despite the genetic defects identified in several candidate genes, in a large proportion of PPOI cases no cause has been found; and hence they are classified as idiopathic PPOI. Considering that initial follicular pool size and the rate of follicular depletion are associated with the age of menopause and given the fact that these germ cells express gonadal steroid receptors at various stages of development, it is plausible that genetic variants in sex hormone receptor genes involved in maintaining ovarian function could affect the risk of PPOI. Estrogen actions mediated through its cognate receptors (ERα and ERβ) are essential modulators of folliculogenesis, directly throught regulation of the hypophyseal-gonadas axis. Sequence polymorphisms of the ERα gene (ESR1: estrogen receptor 1) have been shown to be associated with osteoporosis, unexplained infertility and lower response to ovarian hyperstimulation, and uterine fibroids and endometriosis. A recent study reports that ESR1 gene polymorphisms are associated with PPOI in Korean cohort. Deficiency of estrogen, a critical reproductive hormone for bone acquisition, is associated with an increased bone turnover and accelerated bone loss, leading to the increased susceptibility to osteoporosis and bone fractures. The inheritance of bone mass is under polygenic control.SOHLH 1 and 2 are transcription factors involved in etiology ofPPOI.SOHLH2 gene is situated on chromosome 13 and is testis-specific factor important for spermatogenesis, oogenesis and folliculogenesis. Both, SOHLH 1 and 2,are expressed exclusively in primordial follicles up until the primary follicle stage, and are master regulators of oocyte-specific genes critical for early follicle growth and differentiation..

Učinak dnevne tjelesne aktivnosti na aktivnost upalnih bolesti crijeva kod bolesnika koji ne uzimaju terapiju

It has been suggested that various environmental factors play a very important role in the etiology of inflammatory bowel diseases (IBDs) and that they have a significant effect on the course of these diseases. The aim of this study was to investigate the effect of daily physical activity on the activity of IBDs in therapy-free patients. This cross-sectional population based study was conducted in eastern Croatia from January to June 2016. e study included 312 patients, mean age 49.9±15.0 years, 53.2% of males and 46.8% of females; there were 63.4% of ulcerative colitis (UC) and 36.6% of Crohn’s disease (CD) patients. Sociodemographic characteristics of patients, data on their daily physical activity and type of therapy taken were collected through a specifically designed and validated questionnaire, while the activity of UC and CD was evaluated using the Mayo index and Harvey-Bradshaw index. The study showed that 24.0% of patients were not taking therapy. Daily physical activity was connected to IBD in study patients when taking both diseases collectively (Fisher exact test; p<0.001), as well as to the inactivity of CD (Fisher exact test; p=0.001) and UC (Fisher exact test; p=0.006), when observing each disease separately. Daily physical activity was connected to the inactivity of IBDs in patients not taking therapy. It is necessary to educate all IBD patients about the importance of physical activity in order to control their disease.Smatra se kako različiti okolišni čimbenici igraju vrlo važnu ulogu u etiologiji upalnih bolesti crijeva (UBC) te kako imaju značajan učinak na tijek ovih bolesti. Cilj ovog istraživanja bio je ispitati učinak dnevne tjelesne aktivnosti na aktivnost UBC kod bolesnika koji ne uzimaju terapiju. Ovo presječno populacijsko istraživanje provedeno je u istočnoj Hrvatskoj od siječnja do lipnja 2016. godine. Istraživanje je obuhvatilo 312 bolesnika srednje dobi 49,9±15,0 godina; 53,2% muškaraca i 46,8% žena; 63,4% oboljelih od ulcerativnog kolitisa (UC) i 36,6% oboljelih od Crohnove bolesti (CB). Sociodemografska obilježja bolesnika, podaci o njihovoj dnevnoj tjelesnoj aktivnosti i vrsti terapije koju uzimaju prikupljeni su pomoću posebno dizajniranog i validiranog upitnika, dok je aktivnost UC i CB ocijenjena primjenom indeksa Mayo i indeksa Harvey-Bradshaw. Istraživanje je pokazalo kako 24,0% bolesnika ne uzima terapiju. Dnevna tjelesna aktivnost bila je povezana s neaktivnom UBC kod bolesnika kada su zajednički promatrane obje bolesti (Fisherov egzaktni test; p<0,001) te je bila povezana s neaktivnošću CB (Fisherov egzaktni test; p=0,001) i UC (Fisherov egzaktni test, p=0,006) kad je svaka bolest promatrana zasebno. Dnevna tjelesna aktivnost povezana je s neaktivnošću UBC kod bolesnika koji ne uzimaju terapiju. Potrebno je sve bolesnike s UBC podučiti o važnosti tjelesne aktivnosti za kontrolu njihove bolesti

Predominant types and clinical characteristics of vestibular disorders in schoolchildren

Periferni vestibularni poremećaji u djece značajno utječu na školski i športski uspjeh, ponašanje kao i kakvoću života u djece, a prevalencija im doseže i do 15%. Simptome vrtoglavice djeca opisuju drukčije od odraslih, a u odnosu na odrasle različita je distribucija najčešćih perifernih vestibularnih poremećaja. Između 2010. i 2017. godine retrogradno smo analizirali medicinsku dokumentaciju 57-ero djece u dobi od 6 do 12 godina, koja su u sklopu audiološke poliklinike obrađivana zbog vrtoglavice i smetnji ravnoteže. U djece školske dobi najčešće su zastupljeni benigni paroksizmalni vertigo (BPV) i vestibularna migrena (VM). Ménièreova bolest (MB) i benigni pozicijski paroksizmalni vertigo (BPPV) nisu učestali u školske djece.The prevalence of peripheral vestibular disorders in children is up to 15% with high impact on school performance, sports and balance, behaviour and quality of life. Children complaints regarding vertigo and dizziness are diff erent from those in adult population and there is diff erent distribution of the most common types of vestibular disorders. We analyzed a medical records of 57 children aged 6 to 12 years admitted to our audiology clinic with vertigo and dizziness symptoms between January 2010 and June 2017 in order to determine the most common types of vestibular disorders presenting in schoolchildren and the most common clinical characteristics related to them. We found benign paroxysmal vertigo and vestibular migraine to be the most common causes of peripheral vestibular disorders in the school-age population. Ménière’s disease and benign positional paroxysmal vertigo were not frequent causes of vertigo in schoolchildren

THE IMPACT OF HYPOGLYCEMIA AND EPA AND DHA SUPPLEMENTATION ON BRAIN-DERIVED NEUROTROPHIC FACTOR LEVEL IN PREGNANT WOMEN WITH TYPE 1 DIABETES: A PROSPECTIVE COHORT STUDY

Background: In addition to its neuroprotective effect, Brain-derived neurotrophic factor (BDNF) also plays a role in glucose and lipid metabolism. This study aims: a) to find changes in the BDNF concentration during pregnancy in type 1 diabetes. b) to prove the effect of DHA and EPA supplementation on changes in BDNF concentrations c) to investigate the impact of hypoglycemia on BDNF concentration. Subjects and methods: The data from this study were from the PRE-HYPO cohort study. Twenty-one of them were on a standard diabetic diet enriched with EPA and DHA (EPA 120 mg/day and DHA 616 mg/day; Exposed group), and nineteen pregnant diabetic women were on the standard diabetic diet without EPA and DHA supplementation (Non-exposed group). In the first trimester of pregnancy, fift .9 mmol/L; HYPO+ group), and twenty-five pregnant women did not have hypoglycemia episodes (HYPO- group). Results: BDNF concentration significantly decreased during pregnancy from the first to the third trimester, in Non-exposed from 25.1 (22.0-30.2) to 22.1 (16.3-28.2), P<0.05, in the Exposed group from 22.1 (19.8-25.9) to 18.1 (14.8-18.9), P<0.01. Pregnant patients with hypoglycemia episodes (HYPO+ subgroup) had significantly higher BDNF in the third trimester of pregnancy [22.5 (20.6-28.4)] when compared with patients who did not develop hypoglycemia [16.3 (14.3-18.8), P<0.001]. In the third trimester of pregnancy, BDNF and n-6 PUFAs were associated with hypoglycemia (OR 1.818 95 % CI 1.079-3.003, P=0.025; OR 1.103 95 % CI 1.001-1.217, P=0.048). Total F.A.s were inversely associated with hypoglycemia (OR 0.969 95% CI 0.939-0.998, P=0.048). Conclusion: Pregnant women with hypoglycemia (HYPO+ group) had higher concentrations of BDNF in the first and third trimesters of pregnancy compared to those without hypoglycemia. An increase in body weight during pregnancy leads to a decrease in BDNF concentration

THE IMPACT OF HYPOGLYCEMIA AND EPA AND DHA SUPPLEMENTATION ON BRAIN-DERIVED NEUROTROPHIC FACTOR LEVEL IN PREGNANT WOMEN WITH TYPE 1 DIABETES: A PROSPECTIVE COHORT STUDY

Background: In addition to its neuroprotective effect, Brain-derived neurotrophic factor (BDNF) also plays a role in glucose and lipid metabolism. This study aims: a) to find changes in the BDNF concentration during pregnancy in type 1 diabetes. b) to prove the effect of DHA and EPA supplementation on changes in BDNF concentrations c) to investigate the impact of hypoglycemia on BDNF concentration. Subjects and methods: The data from this study were from the PRE-HYPO cohort study. Twenty-one of them were on a standard diabetic diet enriched with EPA and DHA (EPA 120 mg/day and DHA 616 mg/day; Exposed group), and nineteen pregnant diabetic women were on the standard diabetic diet without EPA and DHA supplementation (Non-exposed group). In the first trimester of pregnancy, fift .9 mmol/L; HYPO+ group), and twenty-five pregnant women did not have hypoglycemia episodes (HYPO- group). Results: BDNF concentration significantly decreased during pregnancy from the first to the third trimester, in Non-exposed from 25.1 (22.0-30.2) to 22.1 (16.3-28.2), P<0.05, in the Exposed group from 22.1 (19.8-25.9) to 18.1 (14.8-18.9), P<0.01. Pregnant patients with hypoglycemia episodes (HYPO+ subgroup) had significantly higher BDNF in the third trimester of pregnancy [22.5 (20.6-28.4)] when compared with patients who did not develop hypoglycemia [16.3 (14.3-18.8), P<0.001]. In the third trimester of pregnancy, BDNF and n-6 PUFAs were associated with hypoglycemia (OR 1.818 95 % CI 1.079-3.003, P=0.025; OR 1.103 95 % CI 1.001-1.217, P=0.048). Total F.A.s were inversely associated with hypoglycemia (OR 0.969 95% CI 0.939-0.998, P=0.048). Conclusion: Pregnant women with hypoglycemia (HYPO+ group) had higher concentrations of BDNF in the first and third trimesters of pregnancy compared to those without hypoglycemia. An increase in body weight during pregnancy leads to a decrease in BDNF concentration

Uloga omjera E2/P u etiologiji fibrocistične bolesti dojke, mastalgije i mastodinije

The aim of the study was to assess the role of the estradiol and progesterone relationship during the late luteal phase and the occurrence of fibrocystic breast disease (FBD). The concentration of estradiol/progesterone was measured in the group of women with FBD as study group (n=50) and control group of women without FBD (n=40). All women had regular ovulation cycles. Blood samples for estradiol (E2), progesterone (P) and prolactin determination were obtained in the morning at 8 am on days 21 and 24 of menstrual cycle. Significant mastalgia and mastodynia history in women with FBD was obtained with yes or no questionnaire. FBD diagnosis was confirmed with ultrasound (size and number of simple cysts). In the control group, a reduced E2/P ratio was noticed from day 21 to day 24 of the cycle (from 14.8±11.5 pg/mL to 9.1±6.1 pg/mL; p<0.05), which was not recorded in the group of women with FBD (study group). Even the slightest disturbance of the E2/P ratio may contribute to the occurrence of FBD with clinical manifestations of mastalgia and mastodynia.Namjera rada je bila ispitati ulogu odnosa estradiola i progesterona za vrijeme lutealne faze ciklusa u pojavljivanju fibrocistične bolesti dojke (FBD). Koncentracija odnosa estradiol/progesteron je bila mjerena u skupini žena s FBD (n=50) (studijska skupina) i u kontrolnoj skupini žena bez FBD (n=40) (kontrolna skupina). Sve su žene imale redovite ovulacijske cikluse. Krvni uzorci estradiola (E2), progesterona (P) i prolaktina određivali su se u 8 h ujutro 21. i 24. dana menstruacijskog cikusa. Određivanje značajnosti mastalgije i mastodinije bila je ispitana upitnikom da/ne. Dijagnoza FBD je bila potvrđena ultrazvukom dojke (veličina i broj jednostavnih cista). U kontrolnoj skupini smanjen odnos E2/P zabilježen je od 21. do 24. dana ciklusa (od 14,8±11,5 pg/mL do 9,1±6,1 pg/mL; p<0,05), za razliku od žena studijske skupine gdje ta promjena nije bila zapažena. Čak i mala promjena odnosa E2/P može doprinijeti nastanku FBD s kliničkim manifestacijama mastalgije i mastodinije

Individualizacija magistralnog hormonskog liječenja kod bolesnice s kemoterapijom induciranom prijevremenom insuficijencijom jajnika i smanjenom jetrenom funkcijom: prikaz slučaja

Although the use of commercially manufactured hormone therapy (HT) to treat menopausal symptoms has declined during the past 12 years, the use of custom compounded HT seems to have increased. A 39-year-old woman with refractory anemia sustained premature ovarian insufficiency following allogeneic stem cell transplantation. After systemic biologic treatment (azacitidine) and corticosteroid therapy, besides extreme climacteric symptoms (Green Climacteric Scale, 59) and impaired quality of life, she also had elevated liver enzymes. Therefore, she was not a candidate for oral HT. Treatment was started with 17-beta estradiol patch 0.5 mg (Climara) together with micronized progesterone intravaginally, 2x100 mg (Utrogestan) for 3 months. She was not satisfied, so the custom compound HT started with 17-beta estradiol 0.5 mg gel 2x/day and micronized progesterone in liposomal gel 100 mg/daily. She was much better but she complained of low libido, decreased sex drive and emotional instability, so 1% testosterone gel was added. Now she was completely satisfied, Green Climacteric Scale was 8 and liver enzymes were normal. In conclusion, custom compound HT has the possibility of tailoring and adjusting therapy to the individual need, which has been the everlasting goal in menopause medicine and should be a good option for special clinical cases.Premda je upotreba komercijalno pripravljene hormonske terapije u liječenju klimakteričnih simptoma u posljednjih 12 godina u padu, čini se da je upotreba magistralnih hormonskih pripravaka u porastu. Žena u dobi od 39 godina s refraktornom anemijom doživjela je prijevremenu insuficijenciju jajnika nakon transplantacije matičnih stanica. Nakon sistemskog biološkog liječenja azacitidinom i kortikosteroidima, uz izrazite klimakterične tegobe (Greenov indeks 59) i smanjenu kvalitetu života imala je povišene jetrene enzime. Zbog toga nije bila kandidat za oralnu hormonsku terapiju. Započeto je liječenje 17-beta estradiolom u obliku naljepka od 0,5 mg (Climara) zajedno s mikroniziranim progesteronom intravaginalno 2x100 mg (Utrogestan) kroz 3 mjeseca. Nije bila zadovoljna terapijom pa su joj propisani magistralno pripravljeni hormoni. Započelo se s primjenom 17-beta estradiola u obliku 0,5 mg gela 2x/dan i mikroniziranog progesterona u liposomalnom gelu 100 mg/dnevno. Bolje se je osjećala, ali još uvijek se žalila na smanjeni libido i emocionalnu nestabilnost pa je dodan 1% testosteron. Sad je bila potpuno zadovoljna terapijom, Greenova klimakterijska ljestvica bila je 8, a jetreni enzimi su se normalizirali. U zaključku, magistralni hormonski pripravci pružaju mogućnost titracije i prilagođavanja terapije individualnim potrebama, što je stalni cilj u menopauzalnoj medicini i mogao bi biti dobra mogućnost za posebne slučajeve

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

The serotonin receptor 2A gene (HTR2A) is a strong candidate for the fetal programming of future behavior and metabolism. Maternal obesity and gestational diabetes mellitus (GDM) have been associated with an increased risk of metabolic and psychological problems in offspring. We tested the hypothesis that maternal metabolic status affects methylation of HTR2A in the placenta. The prospective study included 199 pairs of mothers and healthy full-term newborns. Genomic DNA was extracted from feto-placental samples and analyzed for genotypes of two polymorphisms (rs6311, rs6306) and methylation of four cytosine residues (−1665, −1439, −1421, −1224) in the HTR2A promoter region. Placental HTR2A promoter methylation was higher in male than female placentas and depended on both rs6311 and rs6306 genotypes. A higher maternal pre-gestational body mass index (pBMI) and, to a lesser extent, diagnosis of GDM were associated with reduced HTR2A promoter methylation in female but not male placentas. Higher pBMI was associated with reduced methylation both directly and indirectly through increased GDM incidence. Tobacco use during pregnancy was associated with reduced HTR2A promoter methylation in male but not female placentas. The obtained results suggest that HTR2A is a sexually dimorphic epigenetic target of intrauterine exposures. The findings may contribute to a better understanding of the early developmental origins of neurobehavioral and metabolic disorders associated with altered HTR2A function

Prikazi

1) Tanja Bukovčan: COVID-19 u humanističkoj perspektivi, Ivana Katarinčić, Jelena Marković, Ines Prica i Ana-Marija Vukušić, ur., Institut za etnologiju i folkloristiku, Zagreb, 2022., 661 str. 2) Melanija Belaj: Đordana Barbarić, Siromaštvo. Mrlja na savjesti čovječanstva. Prikaz okvira i mogućnosti suzbijanja siromaštva u RH, Udruga MoSt, Split, 2020., 77 str. 3) Olga Orlić: Zvjezdana Antoš, Zbirka pokućstva (The furniture collection), Etnografski muzej, Zagreb, 2021., 264 str. 4) Melanija Belaj: Mojca Ramšak, Social Impact of Wine Marketing. The Challenge of Digital Technologies to Regulation, Springer, Cham, 2022., 120 str. 5) Jelena Ivanišević: Katarina Horvat, Kućna služinčad u Zagrebu 1880.–1914., Srednja Europa, Zagreb, 2021., 353 str. 6) Dora Dunatov: Dylan Robinson, Hungry Listening. Resonant Theory for Indigenous Sound Studies, University of Minnesota Press, Minneapolis, 2020., 288 str. 7) Ana-Marija Vukušić: Sanja Đurin, “Hrvati su brend u Čileu”. Diskursi uspješnosti i pripadanja, Institut za etnologiju i folkloristiku, Zagreb, 2020., 213 str. 8) Maja Profaca: Melanija Belaj, Obiteljske fotografije. Kulturnoantropološka perspektiva, Biakova i Institut za etnologiju i folkloristiku, Zagreb, 2020., 175. str

Prikazi

1) Tanja Bukovčan: COVID-19 u humanističkoj perspektivi, Ivana Katarinčić, Jelena Marković, Ines Prica i Ana-Marija Vukušić, ur., Institut za etnologiju i folkloristiku, Zagreb, 2022., 661 str. 2) Melanija Belaj: Đordana Barbarić, Siromaštvo. Mrlja na savjesti čovječanstva. Prikaz okvira i mogućnosti suzbijanja siromaštva u RH, Udruga MoSt, Split, 2020., 77 str. 3) Olga Orlić: Zvjezdana Antoš, Zbirka pokućstva (The furniture collection), Etnografski muzej, Zagreb, 2021., 264 str. 4) Melanija Belaj: Mojca Ramšak, Social Impact of Wine Marketing. The Challenge of Digital Technologies to Regulation, Springer, Cham, 2022., 120 str. 5) Jelena Ivanišević: Katarina Horvat, Kućna služinčad u Zagrebu 1880.–1914., Srednja Europa, Zagreb, 2021., 353 str. 6) Dora Dunatov: Dylan Robinson, Hungry Listening. Resonant Theory for Indigenous Sound Studies, University of Minnesota Press, Minneapolis, 2020., 288 str. 7) Ana-Marija Vukušić: Sanja Đurin, “Hrvati su brend u Čileu”. Diskursi uspješnosti i pripadanja, Institut za etnologiju i folkloristiku, Zagreb, 2020., 213 str. 8) Maja Profaca: Melanija Belaj, Obiteljske fotografije. Kulturnoantropološka perspektiva, Biakova i Institut za etnologiju i folkloristiku, Zagreb, 2020., 175. str