[Uveal Melanoma: Molecular and Genetic Mechanisms of Development and Therapeutic Approaches].

Uveal melanoma (UM) is a neuroectodermal tumor that results from malignant transformation of melanocytes in the eye uvea, including the iris, the ciliary body, and the choroid. UM accounts for 5% of all melanoma cases and is extremely aggressive with half of the UM patients developing metastases within the first 1-2 years after tumor development. Molecular mechanisms of UM carcinogenesis are poorly understood, but are known to differ from those of skin melanoma. Activating mutations of the GNAQ and GNA11 genes, which code for the large G protein subunits Gq and G11, respectively, are found in 90% of UM patients. The Gaq/PKC/MAPK signaling pathway is a main signaling cascade that leads to the transformation of melanocytes of the uveal tract, and major regulators of the cascade provide targets for the development of drugs. Metastatic UM (MUM) is most often associated with mutations of BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. A combination of a commercial expression test panel of 15 genes and a mutation panel of 7 genes, supplemented with data on the size of the primary tumor, is highly efficient in predicting the risk of metastasis. The risk of metastasis determines the choice of therapy and the patient follow-up regimen. However, no systemic therapy for MUM has been developed to date. New drugs undergoing clinical trials are mostly targeted drugs designed to inhibit the protein products of mutant genes or immunotherapeutic agents designed to stimulate the immune response against specific antigens. In addition to these approaches, potential therapeutic targets of epigenetic regulation of UM development are considered in the review.

Social capital and physical activity among Croatian high school students.

OBJECTIVE: To examine factors associated with regular physical activity in Croatian adolescents. STUDY DESIGN: A cross-sectional survey among high school students was carried out in the 2013/14 school year. METHOD: A survey was conducted among 33 high schools in Zagreb City, Croatia. Participants were students aged 17-18 years. The dependent variables were regular moderate to vigorous physical activity (MVPA) and overall physical activity measured by the short version of International Physical Activity Questionnaire and defined as 60 min or more of daily physical activity. The independent variables included family, neighborhood, and high school social capital. Other study covariates included: socio-economic status, self-rated health, psychological distress and nutritional status. The associations between physical activity and social capital variables were assessed separately for boys and girls through multiple logistic regression and inverse probability weighting in order to correct for missing data bias. RESULTS: A total of 1689 boys and 1739 girls responded to the survey. A higher percentage of boys reported performing regular vigorous and moderate physical activity (59.4%) and overall physical activity (83.4%), comparing with the girls (35.4% and 70%, respectively). For boys, high family social capital and high informal social control were associated with increased odds of regular MVPA (1.49, 95%CI: 1.18 - 1.90 and 1.26, 95%CI: 1.02 - 1.56, respectively), compared to those with low social capital. For girls, high informal social control was associated with regular overall physical activity (OR 1.38, 95% CI: 1.09 - 1.76). CONCLUSION: High social capital is associated with regular MVPA in boys and regular overall activity in girls. Intervention and policies that leverage community social capital might serve as an avenue for promotion of physical activity in youth.

Serum preadipocyte factor-1 concentrations in females with obesity and type 2 diabetes mellitus: the influence of very low calorie diet, acute hyperinsulinemia, and fenofibrate treatment.

Appropriate differentiation capacity of adipose tissue significantly affects its ability to store lipids and to protect nonadipose tissues against lipid spillover and development of insulin resistance. Preadipocyte factor-1 (Pref-1) is an important negative regulator of preadipocyte differentiation. The aim of our study was to explore the changes in circulating Pref-1 concentrations in female subjects with obesity (OB) (n=19), females with obesity and type 2 diabetes mellitus (T2DM) (n=22), and sex- and age-matched healthy control subjects (C) (n=22), and to study its modulation by very low calorie diet (VLCD), acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp, and 3 months' treatment with PPAR-α agonist fenofibrate. At baseline, serum Pref-1 concentrations were significantly higher in patients with T2DM compared to control group, while only nonsignificant trend towards higher levels was observed in OB group. 3 weeks of VLCD decreased Pref-1 levels in both OB and T2DM group, whereas 3 months of fenofibrate treatment had no significant effect. Hyperinsulinemia during the clamp significantly suppressed Pref-1 levels in both C and T2DM subjects and this suppression was unaffected by fenofibrate treatment. In a combined population of all groups, circulating Pref-1 levels correlated positively with insulin, leptin and glucose levels and HOMA (homeostasis model assessment) index. We conclude that elevated Pref-1 concentrations in T2DM subjects may contribute to impaired adipose tissue differentiation capacity associated with insulin resistance in obese patients with T2DM. The decrease of Pref-1 levels after VLCD may be involved in the improvement of metabolic status and the amelioration of insulin resistance in T2DM patients.

EGFR Suppression Inhibits the Sphere Formation of MCF7 Cells Overexpressing EGFR.

The epidermal growth factor receptor (EGFR) is an oncogenic tyrosine kinase that is involved in tumor initiation and progression, making EGFR inhibitors and monoclonal antibodies to this receptor essential for anti-tumor therapy. We have previously shown that EGFR transgene expression in the human breast adenocarcinoma cell line MCF7 (MCF7-EGFR) stimulates the 3D spheroid-like growth. The primary focus of our present work was to investigate whether EGFR inhibition could affect the assembly of spheroids or lead to the destruction of pre-existing spheroids. We compared the effects of anti-EGFR siRNA, the anti-EGFR monoclonal antibody cetuximab, and the tyrosine kinase inhibitor AG1478 on dissociated and spheroid MCF7-EGFR cells. MCF7-EGFR cells were found to have a 2.5-fold higher sensitivity towards the cytotoxic effects of cetuximab and AG1478 compared with the parental MCF7 cell line. The suppression of EGFR mRNA with siRNA was found to reduce the sphere formation, whereas treating the pre-existing spheroids had no such effect. Treatment of dissociated spheroids with cetuximab and AG1478 was also found to inhibit the MCF7-EGFR sphere formation. We suggest that EGFR expression is important, at least, during the spheroid formation stage. The transition of a MCF7wt adherent cell culture to MCF7-EGFR spheroids was accompanied by a considerable increase in N-cadherin adhesion proteins. The level of N-cadherin decreased when MCF7-EGFR cells were treated with siRNA and cetuximab. Thus, we have demonstrated that N-cadherin is involved in the EGFR-dependent formation of MCF7-EGFR spheroids. Accordingly, MCF7-EGFR spheroids can be considered a suitable model for studying aggressive hormone-positive breast tumors.

Immunogenic Cell Death in Cancer Therapy.

Apoptosis plays a crucial role in chemotherapy-induced cell death. The conventional theory holding that apoptosis needs to be immunologically silent has recently been revised, and the concept of immunogenic cell death (ICD) has been proposed. This review describes the main features of ICD induction. These ICD markers are important for the effectiveness of anticancer therapy, as well as for basic research into cell death regulation. The mechanism of the "vaccination effect" of dying cancer cells undergoing ICD has been fully described, including the activation of specific antitumor response after re-challenge by the same living tumor cells. This review also discusses the whole set of molecular events attributing cell death to immunogenic type: the exposure of calreticulin and the heat shock protein HSP70 to the outer surface of the cell membrane and the release of the nuclear protein HMGB1 and ATP into the extracellular space. ICD inducers of various nature (chemotherapy drugs, cytotoxic proteins, and oncolytic viruses), as well as physical methods, are classified in the current review.

COMPREHENSIVE RADIOLOGICAL AND HYGIENIC MONITORING OF PARTICULAR SETTLEMENTS OF KYIV REGION IN 2019. / KOMPLEKSNYI RADIATsIINO/GIGIIeNIChNYI MONITORYNG OKREMYKh NASELENYKh PUNKTIV KYÏVS'KOÏ OBLASTI U 2019 ROTsI.

OBJECTIVE: to identificate the main factors and assess their impact on the formation of radiation doses to the population of radioactively contaminated areas of Kyiv region at the current stage of the accident based on complexradiation and hygienic monitoring in the reference settlements in 2019. MATERIALS AND METHODS: Comprehensive radiological and hygienic monitoring was carried out in eight settlementsof Kyiv region - villages of Ragivka, Lygovyky, Mar'yanivka, Zelena Poliana of Polis'kyi district and villages ofHornostaipil, Dytiatky , Pisky, Karpylivka of Ivankiv district. The content of incorporated 137Cs was determined withdirect measurement on whole body counters (WBC) samples of basic foodstuffs were collected to determine the content of radionuclides 90Sr and 137Cs, residents were interviewed about the levels of consumption of these products,and work was performed to estimate external radiation doses. Mathematical, dosimetric, radiochemical methods areused in the work. RESULTS: There was a further decrease in annual doses of internal radiation in the surveyed settlements in 1.3 times, bothin Polis'kyi district (0.041 mSv · year-1 in 2016, 0.030 mSv · year-1 in 2019) and in Ivankiv district (0.023 mSv · year-1in 2016, 0.018 mSv · year-1 in 2019). It is possible to state a slowdown in the reduction of radiation doses comparedto previous years: from 2010 to 2013, the annual doses of internal radiation in the surveyed settlements decreasedby 1.8-2.4 times, from 2013 to 2016 - by 2.3-3.6 times. The content of 137Cs and 90Sr in milk and potatoes in theinspected settlements is lower than the permissible level of the Hygienic Standard HS 6.6.1.1-130-2006 and the useof these foods can not significantly affect the formation of the internal radiation dose. The content of 90Sr in milksamples in the settlements of Ivankiv district is in the range of 2.1-9.9 Bq · kg-1 (in 2016: 1.3-7.4 Bq · kg-1), whichdoes not exceed the permissible level of 20 Bq · kg-1, but due to the dynamics needs further monitoring. The content of 137Cs in samples of dried mushrooms collected from residents of Kyiv region in 2019, as in previous years, issignificantly (up to 100 times) higher than permissible level, and has a high uncertainty - from 1.4 kBq · kg-1 to223.7 kBq · kg-1. CONCLUSIONS: It is established that the annual effective radiation doses of the population in the surveyed settlements in the current year are formed due to internal radiation doses that do not exceed 0.46 mSv · year-1 in Ivankivdistrict and 0.51 mSv · year-1 in Polis'kyi district, which below the RCT criterion 1 mSv · year-1. The main factor that forms the dose of internal radiation of the residents of the surveyed state of emergency of Kyiv region is the intake of 137Cs in the body with forest products, primarily mushrooms.

Lipid monolayer as a simple model membrane for comparative assessment of the photodynamic therapy photosensitizer efficiency via macroscopic measurements.

Cellular membrane is one of the main targets of photodynamic therapy. Its high complexity has led to the study of the efficiency of photosensitizers on artificial lipid systems mimicking membranes. However, the preliminary analysis of this efficiency remains limited due to difficulty of the model construction and/or implementation of the required measurement techniques. Hereby, we propose a quite simple way for the rapid comparative assessment of novel photosensitizers in terms of membrane photodegradation, based on simple and fast measurements, such as wetting angle and surface plasmon resonance spectroscopy. As a proof of concept, we applied this methodology to two bacteriopurpurinimide derivatives. We have shown in particular that such complementary techniques can be employed not only for the multiparametric monitoring of the kinetics of the photodegradation, but also for the comparison of the damaging efficiency of the photosensitizers in the lipid structures as well.

Scanning Tunneling Microscopy and Nanolithography on a Conducting Oxide, Rb0.3MoO3.

The scanning tunneling microscope has been used to image and modify the surface of a conducting oxide (Rb(0.3)MoO(3))in ambient atmosphere. Individual octahedral MoO(6) units of the oxide can be imaged, and under certain conditions defects can be created in the surface that are stable in air. The ability to produce nanometer-sized structures on the surface of an oxide is demonstrated and discussed with reference to nanolithographic applications.

[Red-breasted goose colonies on the Taimyr Peninsula: factors responsible for the proximity of goose nests to nests of peregrine falcons, rough-legged buzzards, and snowy owls].

Red-breasted goose colonies have been studied near Medusa Bay (73 degrees 21' N, 80 degrees 32' E), on the northwestern Taimyr Peninsula, and along the Agapa River (70 degrees 11' N, 86 degrees 15' E) down to its mouth (70 degrees 26' N, 89 degrees 13' E), in the central Taimyr Peninsula. Red-breasted geese nesting near peregrine falcons are protected by the falcons from arctic foxes; however, they are sometimes attacked by the falcons themselves. In the colonies near peregrine falcon nests, the vast majority of goose nests were situated no farther than 100 m from the falcon nest. When food is abundant, falcons protect a larger area around their nest. The distance between the falcon nest and the surrounding goose nests is inversely related to the falcon's activity. In years of higher falcon activity, falcons prevent red-breasted geese from nesting as close to their nest as in years of lower falcon activity. Additional stimuli are required for red-breasted geese to form colonies near rough-legged buzzard nests. The distance between snowy owl nests and red-breasted goose nests was smaller when arctic foxes were abundant than when they were scarce.

[White-fronted and bean geese breeding near snowy owls, peregrine falcons, and rough-legged buzzards at the Taimyr Peninsula].

Studies were carried out in 2000-2007 near Medusa Bay (73.21' N, 80.32' E) and along the Agapa River (from 70 degrees 11', 86 degrees 15' E. down to the mouth 71 degrees 26' N, 89 degrees 13' E), in the northwestern and central parts of the Taimyr Peninsula. White-fronted goose nests are usually spread in the tundra or placed in 1-3 nest colonies near nests or staging points of snowy owls, peregrine falcons, or rough-legged buzzards. The intent of white-fronted geese to breed near birds of prey or owls increases sharply when arctic fox numbers are high. In the area near Medusa Bay, white-fronted geese nest much closer to peregrine falcon nests than in the area along the Agapa River. At the latter location, white-fronted geese lose the competition to red-breasted geese, which are more numerous here. Bean geese, in spite of their greater size and ability to protect their nests against arctic foxes, really tend to breed near peregrine falcons or buzzards, where they manage to compete with red-breasted geese.

EVALUATION OF MAIN FOODSTUFFS CONSUMPTION BY RESIDENTS OF PARTICULAR SETTLEMENTS ON RADIOLOGICALLY CONTAMINATED TERRITORIES OF UKRAINE. / OTsINKA SPOZhYVANNIa OSNOVNYKh KhARChOVYKh PRODUKTIV MEShKANTsIaMY OKREMYKh NASELENYKh PUNKTIV RADIOAKTYVNO ZABRUDNENYKh TERYTORIY̆ UKRAÏNY.

OBJECTIVE: evaluation of main foodstuffs consumption levels of residents in particular settlements on radiological- ly contaminated territories of Kyiv, Rivne and Zhytomyr regions and determination of the proportion of local house- holds products to goods purchased in the trade network in the daily ration. MATERIALS AND METHODS: The research was conducted in 22 settlements of Kyiv, Rivne, Zhytomyr regions. For the study, the questionnaires were written for adults and children, which included 47 questions in 5 content blocks regarding the questionnaire data of the interviewed person; peculiarities of household management; levels of food consumption grown in local households and separately purchased in the trade network; levels of local wildlife products consumption; and the fifth - regarding the possession of information on radiation, received an individual dose of radiation from the «Chornobyl component¼, protective preventive measures. In total 539 people were inter- viewed, including 359 adults and 180 children aged 1 to 18 years. Information about children under 14 years of age was provided by their parents. Mathematical, statistical methods were used. RESULTS: According to the results of the survey, it can be stated that the main foodstuffs of residents of the sur- veyed settlements are milk and dairy products, potatoes and root crops of local cultivation, bread and bakery products purchased in the trade network. The analysis of the structure and dynamics of the diet of the popula- tion of the surveyed settlements showed a significant decrease in the consumption levels of basic food products, primarily purchased through the trade network, due to a decline in purchasing power of the population in recent years. CONCLUSIONS: The diet of the residents of the surveyed settlements consists mainly of products produced in private or local households. Fewer people use wildlife products - wildfowl, fish from local water bodies, fresh and canned wild berries, and fresh and dried mushrooms, but due to their significant 137Cs contamination, even small amounts of these products can result in a significant dose of radiation.

Difficulty adaptation in a competitive arm rehabilitation game using real-time control of arm electromyogram and respiration.

Rehabilitation robots are often combined with serious games that motivate patients and keep them exercising at high intensities. A promising type of game are competitive rehabilitation games, but few difficulty adaptation algorithms have been presented for them. This paper thus presents the adaptation of difficulty in a competitive arm rehabilitation game based on two physiological signals: respiration and electromyography of the posterior deltoid. It consists of three smaller studies: an open-loop respiration study, a closed-loop respiration study (where a controller attempts to maintain respiration rate at preset levels), and a closed-loop electromyogram study (where a controller attempts to keep the electromyogram at preset levels). The studies control two difficulty parameters based on the physiological responses of one of the two exercising participants, though the ultimate goal is to control the physiological responses of both participants. Furthermore, all three studies are done with unimpaired participants. The closed-loop controllers achieved high correlation coefficients between desired and measured levels of respiration rate (r = 0.83) and electromyogram (r = 0.89), demonstrating that it is possible to control the physiological responses of unimpaired participants in a competitive arm rehabilitation game, thus controlling their level of workload and exercise intensity. In the future, the proposed method will be tested with patients undergoing rehabilitation.

SNAT expression in rat placenta.

Amino acid transport System A (SysA) activity is present within the rodent and human placentas. Inhibition of this transport system is associated with fetal growth retardation. Several cDNAs encoding SysA transport proteins have been discovered, and their presence documented within the human placenta. We have demonstrated the presence of mRNA encoding three of these transporters, SNAT1, 2, and 4 within the rat placenta over the final third of gestation. Abundance of these mRNA species increases from day 14 to day 20 of gestation. Immunohistochemistry demonstrates the presence of SNAT1 and 2 within the placental labyrinth at both days 14 and 20. Transport proteins are also present within marginal giant cells and, for SNAT1, within fetal endothelium. In conclusion, several proteins capable of SysA transport activity are present within the rodent placenta. mRNA expression increases over the final third of gestation, coincident with the period of greatest need for fetal amino acid delivery.

Airflow limitation is accompanied by diaphragm dysfunction.

Chronic airflow limitation, caused by chronic obstructive pulmonary disease (COPD) or by asthma, is believed to change the shape and the position of the diaphragm due to an increase in lung volume. We have made a comparison of magnetic resonance imaging (MRI) of diaphragm in supine position with pulmonary functions, respiratory muscle function and exercise tolerance. We have studied the differences between patients with COPD, patients with asthma, and healthy subjects. Most interestingly we found the lung hyperinflation leads to the changes in diaphragmatic excursions during the breathing cycle, seen in the differences between the maximal expiratory diaphragm position (DPex) in patients with COPD and control group (p=0.0016). The magnitude of the diaphragmatic dysfunction was significantly related to the airflow limitation expressed by the ratio of forced expiratory volume in 1 s to slow vital capacity (FEV(1)/SVC), (%, p=0.0007); to the lung hyperinflation expressed as the ratio of the residual volume to total lung capacity (RV/TLC), (%, p=0.0018) and the extent of tidal volume constrain expressed as maximal tidal volume (V(Tmax)), ([l], p=0.0002); and the ratio of tidal volume to slow vital capacity (V(T)/SVC), (p=0.0038) during submaximal exercise. These results suggest that diaphragmatic movement fails to contribute sufficiently to the change in lung volume in emphysema. Tests of respiratory muscle function were related to the position of the diaphragm in deep expiration, e.g. neuromuscular coupling (P(0.1)/V(T)) (p=0.0232). The results have shown that the lung volumes determine the position of the diaphragm and function of the respiratory muscles. Chronic airflow limitation seems to change the position of the diaphragm, which thereafter influences inspiratory muscle function and exercise tolerance. There is an apparent relationship between the position of the diaphragm and the pulmonary functions and exercise tolerance.

Developmental changes in hepatic basolateral membrane lipid composition and fluidity.

Membrane fluidity and lipid composition influence the activity of a variety of membrane proteins. Decreased rates of hepatic ion clearance are associated with the neonatal period. We postulated that hepatic basolateral membranes derived from suckling animals might be less fluid than those from adult animals. Basolateral membrane vesicles were prepared from the livers of 1-week-old (SBLMV) and adult (ABLMV) rats by a Percoll gradient method. Na+/K(+)-ATPase activities were similar in the two groups. Double bond index, cholesterol and cholesterol/phosphorus ratios were significantly higher in SBLMV compared with ABLMV, while lipid phosphorus and relative percentages of phospholipid subclasses did not differ. Fluorescence anisotropy measured using diphenylhexatriene as well as 2-(9-anthroyloxy)stearate was significantly greater in SBLMV compared with ABLMV, while measurements made with 12-(9-anthroyloxy)stearate were similar in both age groups. Mean excited state lifetimes, lifetime distributions, and rotational correlation times were similar in both groups. These data suggest that hepatic basolateral membranes derived from suckling rats are less fluid than those from adult animals and further suggest that this difference may be due to increased cholesterol in hepatic basolateral membranes derived from suckling animals.

The influence of mouse sera, regenerating liver extracts and bacterial products on the abilities of different cells in vitro.

In the complexity of host tumor relations, the regeneration of the tissue in which the tumor is growing, or in some other tissue in the organism, could influence the maturation of tumor cells, i.e. tumor reversion. Clinical observations and experiments on plants, lower animals, or animal embryos, performed by several authors, and our results on the influence of regenerating mouse liver on the abilities of tumor transplanted there or elsewhere in the organism led us to study the in vitro growth of different cells or bacteria exposed to the extracts of normal or regenerating liver and/or sera from these animals. Further, sterile used bacterial media were added to bacterial or cell cultures, respectively. Depending on the model, liver extracts-particularly extracts and sera from mice with regenerating liver-were shown to inhibit radioactive thymidine incorporation in the cells. In these experiments, the number of bacteria or cells per culture was lower than in otherwise treated corresponding cultures. Further, used sterile media of bacterial cultures stimulated the growth of bacteria but inhibited thymidine incorporation into fibrosarcoma cells in vitro. Whether this means that one or several common regulators exist in nature appears as an intriguing, but still completely open question. The idea of controlling tumor growth by using such regulatory growth factors seems very provocative.

Multifractal analysis for grading complex fractionated electrograms in atrial fibrillation.

Complex fractionated atrial electrograms provide an important tool for identifying arrhythmogenic substrates that can be used to guide catheter ablation for atrial fibrillation (AF). However, fractionation is a phenomenon that remains unclear. This paper aims to evaluate the multifractal properties of electrograms in AF in order to propose a method based on multifractal analysis able to discriminate between different levels of fractionation. We introduce a new method, the h-fluctuation index (hFI), where h is the generalised Hurst exponent, to extract information from the shape of the multifractal spectrum. Two multifractal frameworks are evaluated: multifractal detrended fluctuation analysis and wavelet transform modulus maxima. hFI is exemplified through its application in synthetic signals, and it is evaluated in a database of electrograms labeled on the basis of four degrees of fractionation. We compare the performance of hFI with other indexes, and find that hFI outperforms them. The results of the study provide evidence that multifractal analysis is useful for studying fractionation phenomena in AF electrograms, and indicate that hFI can be proposed as a tool for grade fractionation associated with the detection of target sites for ablation in AF.

Immunological studies of the toxic site in ammodytoxin A.

Two monoclonal antibodies against the native ammodytoxin A and four site-directed polyclonal antibodies against synthetic peptides derived from the primary structure of the toxin were prepared in order to estimate the localization of its toxic site. Some of the antibodies neutralized the lethal toxicity of the toxin, thus indicating an approximate position of the toxic or receptor binding site on the molecule that is different from those predicted by comparison with a number of known sequences.

Androgen secretion by Rcho-1 cells is independent of extracellular glutamate concentration.

In primates, progesterone, secreted by the placenta, is important for the maintenance of pregnancy. Androstenedione, a progesterone metabolite, fulfils a similar role in the rodent. Prior work has suggested that glutamate sufficiency and subsequent oxidation is important to placental androgen synthesis, presumably because of the production of NADPH (Trophoblast Res (1993) 7, 77). Rcho-1 cells possess a phenotype similar to that of rat placental giant cells, and secrete androstenedione and progesterone when in the differentiated state (J Endocrinol (1996) 150, 161). Our objective was to determine whether extracellular glutamate concentrations impact hormone synthesis in Rcho-1 cells. Rcho-1 cells were kept in culture under differentiating conditions. Extracellular glutamate concentrations were varied from 0-5 mm, and hormone concentrations assayed by ELISA. Rcho-1 cells secreted both progesterone and androstenedione. There was no direct correlation between the extracellular concentration of glutamate and the secretion of either hormone. Inhibition of transaminases (aminooxyacetic acid) or of glutaminase (6-diazo-5-oxo-l-norleucine) did not alter hormone production. Therefore, extracellular glutamate concentrations did not impact progesterone or androstenedione secretion. These findings may relate to the central position of glutamate in a variety of metabolic pathways, making intracellular depletion of this amino acid difficult to accomplish, or may represent a species specific difference in regulation.

Glutamine transport in human and rat placenta.

Glutamine plays an important role in fetal nutrition. This study explored the transport of [3H]glutamine into apical and basal predominant membrane vesicles derived from rat and human placenta. Na+-dependent glutamine transport was present in both apical and basal predominant vesicles derived from 20- and, to a lesser degree, 14-day gestation rat placenta. Amino-acid transport systems A, ASC-like, B(o,+) (in apical membrane vesicles) and, perhaps, y+L were involved in Na+-dependent glutamine transport. Na+-dependent glutamine uptake into human placental microvillus and basolateral membrane vesicles also occurred via several distinct transport activities. Glutamine transport via system N was not detected in either rat or human placental preparations. Na+-dependent glutamine transport in the rat was more pronounced in basal as compared to apical membrane vesicles. Conversely, in the human preparations, activity was significantly higher in microvillus as compared to basolateral membrane vesicles. It is concluded that Na+-dependent glutamine transport occurs through a variety of transport agencies in both the rat and human placenta. Transport varies with ontogeny and between species.