Low placental angiotensin-converting enzyme expression is related to fetal small for gestational age but not to metabolic control in type 1 diabetic pregnancies.

The maternal renin-angiotensin system is involved in blood pressure control and plays a crucial role in fetoplacental nutrition. Pre-gestational type 1 diabetes (PGDM) leads to serious pregnancy complications. We thus performed a longitudinal study to analyse the association of maternal angiotensin-converting enzyme (ACE) serum levels and placental mRNA expression with fetal newborns gestational weight in type 1 diabetes mellitus (T1DM) women. We recruited 65 singleton pregnant women with T1DM. Placental mRNA ACE gene expression was examined using quantitative real-time PCR. Serum ACE levels were measured in the first, second and third trimesters of pregnancy by ELISA commercial kits. Placental expression of ACE mRNA was significantly lower in small for gestational age (SGA) than appropriate for gestational age (AGA) and large for gestational age (LGA) mothers (0.55±0.06 vs 0.78±0.06 and 0.85±0.07 respectively, p=0.003). In the SGA group, the mRNA expression of ACE positively correlated with maternal body mass index (BMI) in the third trimester (r=0.49; p=0.04). In all study groups maternal ACE level was significantly higher in the third trimester (mean 139.91±SD 69.64) compared to the first and second trimesters of pregnancy (13.57±4.32 and 15.69±15.92 respectively). Our data suggest that lower placental ACE gene mRNA expression may have a vital role in the etiology of SGA babies.

The Importance of New Generation Sequencing (NGS) HLA Typing in Renal Transplantation-Preliminary Report.

INTRODUCTION: Thanks to new generation sequencing (NGS) and expansion of HLA typing with additional loci, it will be possible to increase the effectiveness of graft survival and to avoid complications related to the immune system. New pharmacogenetic factors are still being researched to develop better immunosuppressive treatment. MATERIAL AND METHODS: The incidence of polymorphic HLA loci variants was established, based on a high-resolution NGS method in kidney graft recipients. Furthermore, haplotypic analysis between examined loci was conducted to type additional loci that may influence the transplantation result. A total of 120 kidney recipients were enrolled in the study. A commercial DNA extraction kit in Tubes (QIAamp DNA Blood Mini Kit Qiagen, Germany) was used to isolate DNA from the blood. Sequencing library preparation was done with TruSight HLA set. The Conexio computer program was used to analyse the results of HLA typing. RESULTS: The patients with alleles A*02:01:01, B*44:02:01, C*03:03:01, C*01:02:01, C*05:01:01, C*07:02:01, DQB1*03:03:02, DQB1*06:04:01, or with haplotypic variation A*25:01:01-B*18:01:01- C*15:01:01 were taking the highest doses of cyclosporine (CsA), in contrast to patients with allele B*18:01:01, DQB1*06:02:01, DQB1*02:02:01, or haplotypic variation A*02:01:01- B*44:02:01-C*01:01:01, who were taking the lowest doses. The highest dose of tacrolimus (TAC) was administered to patients with alleles A*68:01:02, A*29:01:01, B*07:02:01, B*35:02:01, B*38:01:01, DRB1*12:01:01, DQB1*05:03:01, or haplotypic variations A*02:01:01-B*57:01:01-C*07:01:01, A*03:01:01-B*07:02:01-C*13:01:01, A*29:02:01-B*44:03:01- C*07:01:01, and A*01:01:01-B*08:01:01-C*03:01:01. Additionally, it was established that HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DPA1, and HLA-DQA1 show very slight polymorphism, which suggests that there is no need for their typing for transplantation purposes. Moreover, loci HLA-C, HLA-DQB1, and HLA-DPB1, which are not routinely examined in recipient-donor matching, show genetic variability that may increase the risk of transplant rejection or shortened graft life. CONCLUSIONS: Expanding the qualification procedure to include allele genotyping could allow clinicians to establish immunosuppressive treatment schemes that would be optimally suited for recipients' phenotype.

The influence of the tumor necrosis factor-alpa-308G>A polymorphism on the efficacy of immunosuppressive therapy in patients after kidney transplantation.

Cytokines play an important role in the immune response. The calcineurin inhibitors (cyclosporine CsA, tacrolimus TAC) widely used after renal transplantation to prevent allograft rejection are immunosuppressive drugs suppressing the production of cytokines. These drugs are characterized by interindividual variability and require monitoring their blood concentrations to predict their optimal dosage. Therefore, the aim of the study was to determine the correlation between therapeutic effects of immunosuppressants and the tumor necrosis factor-α (TNF-α)-308G>A polymorphism in renal transplant patients. A total of 412 patients receiving TAC and CsA were included in the study. Genotype frequencies were determined using the real-time PCR method. Patients with the GG genotype received higher doses of TAC as compared to carriers of the GA genotype (5.24 mg versus 3.35 mg) and had lower mean drug concentration in blood (5.86 ng/ml versus 6.92 ng/ml). Similar results were also obtained for CsA (GG: 185.33 mg versus GA: 153.30 mg, P < 0.05). The comparison of the TNF-α-308G>A polymorphism with the biochemical parameters did not reveal a potential risk for transplant rejection. These results indicate that the TNF-α-308G>A polymorphism may influence the dosage of immunosuppressive drugs in patients after transplantation as far as individualization of drug therapy is concerned.

Polymorphisms of OPG and their relation to the mineral density of bones in pre- and postmenopausal women.

OBJECTIVES: The aim of the study was to evaluate the frequency of gene polymorphisms OPG -163A/G, -950T/C and 1181G/C, assessing their relations with the clinical parameters of osseous turnover and the degree of postmenopausal osteoporosis. STUDY DESIGN: The study included 800 women of postmenopausal (505) and reproductive (295) age from Poland. The postmenopausal group included women with osteoporosis and osteopenia, as well as healthy individuals. All the women of reproductive age were healthy. The frequency of the tested gene polymorphisms was evaluated within the group where BMD (bone mineral density) was marked and also in the control group. MAIN OUTCOME MEASURES: The frequencies of the polymorphisms of OPG genotypes in the women were characteristic of the population. RESULTS: OPG -950T/C polymorphism has been associated with body weight and birth weight. OPG 1181G/C and OPG -163A/G polymorphisms have been associated not only with body weight and birth weight, but also with reduced bone density and an increased risk of postmenopausal osteoporosis. CONCLUSIONS: Evaluation of the polymorphism -950T/C of the OPG gene showed that the CC genotype may appear as an increased risk factor for the faster loss of bone mass and the onset of osteoporosis in Polish postmenopausal women. This polymorphism may be a genetic marker that is responsible for the development of osteoporosis. The homozygous genotypes of polymorphisms 1181G/C and -163A/G of the OPG gene may play a role in increased risks of osteoporosis and may be linked to the birth weights of women.

Polymorphism of vitamin D3 receptor and its relation to mineral bone density in perimenopausal women.

UNLABELLED: Postmenopausal osteoporosis is the most common metabolic bone disease with important genetic factors. We evaluated the frequency of polymorphism 283G/A of the vitamin D3 VDR gene receptor. The study included 800 women at the postmenopausal (505) and reproductive (295) age. Statistically significant changes, depending on the genotype, were shown. INTRODUCTION: Postmenopausal osteoporosis is the most common metabolic bone disease of strong genetic origin with population variability determined by the interaction of genetic and environmental factors. Recognition of different genetic variants underlying development of osteoporosis would make it possible to administer individual symptomatic treatment as well as early prophylactics of osteoporosis. METHODS: The aim of the study was to evaluate the frequency of polymorphism 283G/A of the vitamin D3 VDR gene receptor and assessment of its relations with the clinical parameters of osseous turnover and degree of postmenopausal osteoporosis. The study included 800 women at the postmenopausal (505) and reproductive (295) age throughout the Wielkopolska region in Poland. The postmenopausal group included women with osteoporosis and osteopenia and the healthy ones. Women at the reproductive age were healthy. Frequency of the tested gene polymorphism was evaluated in the group where bone mineral density (BMD) was marked and in the control group. RESULTS: The obtained test results pointed to correlation of polymorphism VDR 283G/A with the BMD scores for the lumbar vertebrae in women with osteopenia and osteoporosis, therefore the ones at risk of fractures. Vitamin D receptor (VDR) polymorphism correlated with reduced BMD values. CONCLUSIONS: Polymorphism 283G/A of the vitamin D3 receptor gene has been proved to be the genetic factor of postmenopausal osteoporosis. The polymorphism mentioned above has been proved to be a factor of mineral bone density changes of women.

CATECHOLAMINES AND ß2-ADRENOCEPTOR GENE EXPRESSION BEFORE AND AFTER MAXIMAL INCREMENTAL CYCLE TEST IN YOUNG ICE HOCKEY PLAYERS: RELATION TO WORK PERFORMED.

The aim of this study was to assess the plasma adrenaline and noradrenaline concentrations as well as whole blood ß2-adrenoceptor gene (ADRB2) expression in young ice hockey players before and immediately after exercise in relation to performed work. Nineteen Youth National Team ice hockey players were subjected to the maximal incremental cycloergometer exercise. The test was done in the pre-competitive phase of training. Among many parameters the plasma adrenaline and noradrenaline concentrations and ADRB2 gene expression in peripheral blood mononuclear cells (PBMC) were determined before and after exercise. The average performed work was 3261.3 ± 558.3 J · kg(-1) and maximal oxygen consumption (VO2max) for all players was 53.85 ± 3.91 mL · kg(-1) min(-1). The geometric mean of the ADRB2 gene expression was statistically significantly different before and after exercise (P ≤ 0.05), while adrenaline and noradrenaline levels in plasma significantly increased after exercise. In the analysed group of athletes we found that initial level of plasma noradrenaline correlated with the performed work (r = - 0.55, P < 0.014) and normalized ADRB2 expression before the exercise correlated with the work done by them (r = 0.48, P<0.039). However, no statistically significant correlations were found between the plasma adrenaline or noradrenaline concentrations and ADRB2 gene expression in peripheral blood of the players. The performed work in the maximal incremental exercise test of regularly training young ice hockey players depends on the initial levels of noradrenaline in plasma and ADRB2 mRNA in PBMC.

The effect of standardized Echinacea purpurea extract on rat cytochrome P450 expression level.

It is claimed that application of botanical supplements or herbal medicinal products with synthetic drugs that are cytochrome P450 enzymes substrates may induce significant herb-drug interactions and may alter pharmacotherapy. Echinacea preparations are one of the best selling products in the Europe and their medicinal use is still increasing but data about interactions of Echinacea extract with CYP enzymes are limited. In this study, we have investigated potential influence of standardized Echinacea purpurea extract containing 3.7% polyphenolic compounds on the mRNA expression level of major CYP450 enzymes using animal model. Total RNA was isolated from the rat liver tissue according to the manufacturer's protocol. Complementary DNA was synthesized from a mature mRNA template using reverse transcription. The level of mRNA expression in liver was analyzed by real-time quantitative PCR using specific target primers for CYP450 genes. In this study, it was demonstrated a significant increase of rat CYP2D1 and CYP1A1 expression level by 40% (p = 0.007) and 80% (p = 0.01), respectively. A weak inductory effect of the extract was observed for CYP1A2 by 16% (p > 0.05) compared with the control group. The levels of rat CYP3A1 and CYP3A2 mRNA were reduced by 41% (p < 0.05) and 25% (p = 0.001), respectively. A weak inhibitory effect was observed for CYP2D2 by 15% (p = 0.008) and CYP2C6 by 18% (p = 0.004) after long application of the Echinacea ethanolic extract. CYP2D2 and CYP2C6 activities were also inhibited by extract but in a lesser degree than CYP3A1 activity. Moreover, very little or no inhibition was noted for CYP2E1 both after 3 and 10 days of treatment. Our in vivo data indicate that the Echinacea ethanolic extract can potently inhibit the expression of CYP3A1/2 and can also induce of CYP1A1, CYP2D1. These findings suggest that Echinacea extract may influence the P450-mediated metabolism of different drugs and may initiate chemical carcinogenesis by activation of some compounds to their carcinogenic metabolites.

[Some stomatologic health problems in elderly persons]. / Niektóre stomatologiczne problemy zdrowotne osób w podeszlym wieku.

The year 1999 was acclaimed The Year of Ripe Age by WHO. On account of this, attention should be paid to problems related to changes within the oral cavity tissues, mandibular and circummandibular bones, which progress together with the process of ageing. These changes may be due to physiological involutional processes or due to increasing tendencies towards various pathological changes. In general opinion the loss of teeth, which do not need to be treated, is the end of basic diseases and dental problems only concern prosthetic supplements. Obligatory, periodic dental examinations are not imposed on the population of old people. Thus, the only possibility of early diagnosis of morbid processes within tissue structures of the oral cavity, is general examination including a detailed inspection of the oral cavity, even if the patient does not complain about any indisposition.

[Geographic differences in iodine supply in the Silesia terrain in relation to thyroid cancer risk]. / Zróznicowanie geograficzne podazy jodu na ternie województwa slaskiego w aspekcie ryzyka raka tarczycy.

Risk factors associated with differentiated thyroid carcinoma depend on its histotype. Follicular carcinoma is described as a predominant type in the areas with iodine deficiency, in opposite to papillary thyroid cancer. The incidence of thyroid cancer and its histotypes varies considerably throughout Silesia (data obtained from the Institute of Oncology Cancer Register, Gliwice). The factors responsible for these differences are unknown. The aim of our study was to evaluate the present iodine supply in Silesia region and to relate it to the incidence of the various histotypes of thyroid carcinoma. Urinary iodine excretion observed in 7-11 year-old-children was used as a parameter of iodine supply and measured in the group of 1037 school children in sixteen localities, equally dispersed throughout Silesia. Urine samples were obtained to measure iodine concentration by the modified Sandell-Kolthoff's catalytic method. Mean incidence rates of papillary and follicular thyroid carcinoma were calculated for regions of Silesia by averaging the rates of the communities in each region. Despite the intensive iodine prophylaxis the persistent symptoms of iodine deficiency were observed. There were significant differences in children's ioduria among investigated regions. The percentage of low ioduria (lower then 100 micrograms/l) varied from 35.7% to 87.7%. We observed no correlation between age-adjusted rates for histotypes of thyroid carcinoma and the percentage of urine iodine below 100 micrograms/l, which served as an estimation of iodine deficiency. Our study indicates that Silesia is still an area of moderate iodine deficiency. We were unable to explain the factors responsible for the observed differences in the incidence rates of papillary and follicular thyroid carcinoma.

Oculomotor phenomena in petit-mal.

OBJECTIVE: To determine the temporal relationship among behavior, eye movements and respiration during absence seizures. METHOD: This included simultaneous videorecording of a patient's face, EEG and respirogram, in 5 patients with absence seizures. Absence seizures were defined as a sudden lapse of consciousness with impairment of mental functions. Oculomotor phenomena consisted of: eye fluttering, eye deviation (conjugate lateral or upward deflection), and eye-opening. RESULTS: Oculomotor phenomena began 1 2/3-3 s after the onset of the electrographic discharge and ended before the discharge. The most frequent events were eye-opening, stare with or without palpebral myoclonias, and tonic or clonic upward movements. Downward movement or convergence was not observed as well as head version. Respiratory changes (apnea) are the last events to occur. CONCLUSIONS: absence seizures were characterized by the onset of a 3/s spike-slow wave discharge followed by oculomotor phenomena and respiratory changes. The time course suggests that epileptic discharges precede and then involve oculomotor and respiratory brainstem centers.

Attempt to identify hemolymph nodes in humans.

In the study, nodi limphatici pancreaticolienales obtained from 10 cadavers aged 30-70 years were analyzed. The death causes were other than proliferative diseases of lymphatic and hemopoietic systems, or gastrointestinal tract diseases. After fixation in Bouin fluid, dehydration and embedding in paraffin, 10 microns sections were prepared and subsequently stained with hematoxylin-eosin. Additionally, hemosiderin reaction was performed on specimens from each analysed node. Positive hemosiderin reaction was found in none of the specimens. Certain theoretical aspects relating to hemolymph nodes were also presented in the paper. The authors conclude that there are no hemolymph nodes in the proximity of human splenic vessels.

Visual evoked potentials and brain stem auditory potentials in Friedreich's ataxia--a longitudinal study.

Six patients with Friedreich's ataxia, 4 males and 2 females, their ages ranging from 13 to 33 years, were studied. The early manifestations started between age 7 and 13 with an evolution time between 6 and 20 years. Serial visual and brain stem auditory evoked potential recordings were made. A progressive increase in latency, reduction in amplitude and in latency inter-ocular difference of P100 were observed. The pattern of the reversal checker-board visual evoked potential was preserved. A disorganized BAEP pattern, a well defined potential I, a very small potential V and a delay in the interpeak latency were constant findings. The assumption is made of a progressive involvement of both visual and central auditory pathways. Pathophysiological mechanisms are discussed.

Saccadic eye movements in frontal lesion and posthemispherectomy in humans. An electro-oculographic study.

This study was concerned with the assumed role that the frontal eye fields could play in the mechanisms of: the voluntary saccade optokinetic responses. Ten patients with frontal lobe tumors (8 unilateral, 2 bilateral) and two patients with a right hemispherectomy were studied. EOG and EEG were performed in the same session. Left and right voluntary saccadic potentials could be recorded in all cases, no matter where the frontal lesion was located. Minor differences in amplitude were observed between the fast eye movement to the lesion and to the normal side. Horizontal optokinetic responses to a moving drum were a constant finding in all cases. The frequency and amplitude of the fast component of the responses did not show substantial differences with the drum moving to the lesion or to the healthy side. Voluntary saccadic eye movements to the left and left horizontal optokinetic responses to a moving drum to the right, were recorded in the two cases with a right hemispherectomy. The hypothesis that considers frontal eye field as the pulse generator area for the voluntary or reflex saccadic eye movements is discussed.