Changes in placental angiogenesis and their correlation with foetal intrauterine restriction.

TYPE OF STUDY: Summary review. SETTING: Department of Gynaecology and Obstetrics, 1st Faculty of Medicine, Charles University and Hospital Na Bulovce, Prague; Department of Physiology, Faculty of Science, Charles University, Prague; Department of Children and Adolescent Medicine, 1st Faculty of Medicine, Charles University in Prague and General Teaching Hospital, Prague. INTRODUCTION: Intrauterine growth restriction (IUGR) is one of the most common problems in obstetrics. Its incidence is ranging between 3-10%, according to the type of study population and chosen criteria. The cutoff value mainly used for defining the IUGR is weight below the 10th percentile for gestational age. The minority of authors defines the cutoff value under the 5th or 3rd percentile. Any pathological interference with normal vascular development of placenta may have a critical impact on foetal growth and development. Ischaemia is the most common cause of IUGR in normally well-supplied placenta. IUGR is then a consequence of insufficient extension, branching, and dilatation of capillary loops during the formation of terminal villi. METHODS: This paper is a review focused on up-to-date-known data concerning changes in placental angiogenesis and their impact on IUGR development. CONCLUSION: The aim of this review is to summarize the knowledge concerning the mechanisms of development of the vascular supply to the placenta under physiological conditions and in conditions that result in IUGR.

Bad and Bid - potential background players in preneoplastic to neoplastic shift in human endometrium.

The most common malignancies of the female genital tract are endometrial carcinomas, whose are generally proceeded by hyperplasia. The maintenance of tissue homeostasis is to great extent governed by apoptosis, whose defects can lead to the preneoplastic and/or cancerous changes. Endometrial apoptosis involves among others three groups of proteins of the Bcl-2 family. First group contains anti-apoptotic proteins (e. g. Bcl-2, Bcl-xL). The other two groups belong to the pro-apoptotic proteins with three (e. g. Bax, Bak) or one (e. g. Bad, Bid) so-called BH domains. Bad and Bid trigger the oligomerization of Bak and Bax protein, which permeabilize the outer mitochondrial wall. Unlike Bid, Bad cannot directly trigger apoptosis. Instead, Bad lowers the threshold at which apoptosis is induced, by binding anti-apoptotic Bcl-2 proteins. However, their mutual counterbalance or synergism in the human endometrium has not been reported yet.In this study, the levels of Bid and Bad were measured using SDS-PAGE and Western blotting with specific antibodies, with the aim to analyse expression of Bid and Bad proteins in normal (NE), hyperplastic (HE) and cancerous (CE) endometrium. We demonstrated that Bid expression in CE reached only 47% and 50% of this observed in NE and HE. Conversely, Bad expression in HE reached only 40% and 36% of this observed in NE and CE, respectively. We detected no significant changes of Bid expression between HE and NE, and levels of Bad protein were not different between CE and NE.Trend of Bid and Bad protein expression is clearly opposite in HE and CE. We hypothesise that disrupted apoptotic program in CE seems to be reduced further by lowering levels of direct apoptotic trigger protein Bid. We suggest that the adenocarcinoma tissue of human endometrium thus tries to strengthen its apoptotic effort by lowering the apoptotic threshold via higher Bad levels.

[Blockade of calcium channels - a perspectiveof male contraception?]. / Blokáda vápníkových kanálu - perspektiva muzské antikoncepce?

Besides condoms and vasectomy with their own limitations, no other reliable methods of contraception are available to men. Ion channels play a key role in maturation, capacitation and acrosome reaction of sperms. Blockade of calcium channels with pharmacological inhibitors or compounds isolated from plant extracts might be suggested as one of promising mechanisms of future male contraceptives.

[Selective progesterone receptor modulators and their therapeutical use]. / Selektivní modulátory progesteronového receptoru a jejich terapeutické vyuzití

Currently developed selective progesterone receptor modulators (SPRMs) are steroid derived compounds with a bulky radical substitution at carbon 11. They interact with progesterone receptor and exert antagonistic or/and agonistic effects. Mifepristone was approved for pregnancy termination and ulipristal acetate as emergency contraception and pharmacological therapy of uterine fibroids. SPRMs inhibit endometrial proliferation and myoma growth, this suggests a therapeutical effect in cases of endometriosis and other estrogen-dependent diseases.

Changes in expression of some apoptotic markers in different types of human endometrium.

The maintenance of tissue homeostasis and highly balanced counteraction of cellular proliferation and apoptosis are essential for tissue integrity. In our study, we evaluated the expression of apoptosis- regulating proteins Bcl-2, Bax and PARP, and executive apoptotic enzyme caspase-3 in normal, atrophic, hyperplastic and cancerous endometrium. Endometrial samples were obtained from patients who underwent curettage, hysteroresection or hysterectomy. The protein levels were quantified by immunoblotting. We observed a higher level of important apoptotic enzyme pro-caspase-3 and its active form in hyperplastic and cancerous endometrium, when compared to normal endometrium. The value of Bcl-2/Bax ratio, which reflects cellular resistance to apoptosis, was determined as > 1 for cancerous, normal, and atrophic endometrium. Thus, the effort to eliminate pre-neoplastic and neoplastic cells by apoptosis indicated by high pro-caspase-3 and caspase-3 levels seems to be overcome by a greater proliferative adjustment suggested by higher Bcl-2/Bax ratios in the samples examined. The PARP levels did not vary significantly among the groups. The levels of all examined proteins were significantly lower in atrophic endometrium. Our results suggest that pre-neoplastic and neoplastic states of human endometrium are not influenced simply by changes in apoptosis, but may also be affected by cellular proliferation. A high Bcl-2/Bax ratio as observed in cancerous endometrium can point to deregulation of apoptotic programmes. Thus, the onset and progression of endometrial malignancy could be linked to increased cellular proliferation with defects in apoptotic control.

[Significance of hysteroscopic resection in diagnostics of endometrial cancer]. / Význam resektoskopie v diagnostice karcinomu endometria.

OBJECTIVES: Endometrial cancer is the second most common malignancy of the female genital tract. Its incidence in the Czech Republic is 32/100 000 women and year with a permanent increasing tendency. In comparison with incidence, its mortality remains relatively low, with mortality ratio of 6.7 per 100,000 women and year. The decrease in mortality might be explained predominantly by early diagnostics. The most controversial issue is the potential risk of microscopic extrauterine dissemination of cancerous cells within the peritoneal cavity and circulation during hysteroscopy, and the question if the relatively high pressure of distension medium used during hysteroscopies may or may not multiply the risk. DESIGN: Retrospective study. MATERIALS AND METHODS: Totally, 400 endometrial biopsies were collected during years 2007-2009 at our clinic. In 56 patients, endometrial cancer was diagnosed. Afterwards, 44 women underwent surgery, during which peritoneal washing (lavage) and cytological examination were done. RESULTS: Fifty-six patients with histologically verified endometrial carcinoma were studied. The samples examined in the study were classified by grading as follows: G1 n=34, G1-2 n=10, G2 n=10, G3-4 n=2. In 44 cases that underwent radical surgery, no cancerous cells in peritoneal washings were found. Only in 1 case, the cytology obtained from peritoneal washing was considered to be suspicious. In 9 cases, carcinoma on the base of the polyp was detected, and in 2 cases, no residuum of cancer was observed after hysterectomy. CONCLUSION: In accordance with contemporary literature and based on our study, we suggest that hystero-resectoscopy does not increase the risk of dissemination of malignant cells within the peritoneal cavity and does not worsen the prognosis of the disease. On the contrary, the samples taken under visual control provide more precise and earlier diagnostics of endometrial cancer.

Participation of electrogenic Na+-K+-ATPase in the membrane potential of earthworm body wall muscles.

The effect of Na+-K+-ATPase inhibitor ouabain on the resting membrane potential (Vm) was studied by glass microelectrodes in isolated somatic longitudinal muscles of the earthworm Lumbricus terrestris and compared with frog sartorius muscle. In earthworm muscle, Vm was -49 mV (inside negative) in a reference external solution with 4 mmol/l K+. The electrogenic participation of Na+-K+-ATPase was absent in solutions with very low concentrations of 0.01 mmol/l K+, higher in 4 and 8 mmol/l K+ (4-5 mV) and maximal (13 mV) in solutions containing 12 mmol/l K+ where Vm was -46 mV in the absence and -33 mV in the presence of 1 x 10(4) M ouabain. The electrogenic participation of Na+-K+-ATPase was much smaller in m. sartorius of the frog Rana temporaria bathed in 8 and 12 mmol/l K+. The results indicate that the Na+-K+-ATPase is an important electrogenic factor in earthworm longitudinal muscle fibres and that its contribution to Vm depends directly on the concentration of K+ in the bathing solution.

Biochemistry of transmembrane signaling mediated by trimeric G proteins.

Many extracellular signals are at the cell surface received by specific receptors, which upon activation transduce information to the appropriate cellular effector molecules via trimeric G proteins. The G protein-mediated cascades ultimately lead to the highly refined regulation of systems such as sensory perception, cell growth, and hormonal regulation. Transmembrane signaling may be seriously deranged in various pathophysiological conditions. Over the last two decades the major experimental effort of our group has been devoted to better understanding the molecular mechanisms underlying transmembrane signaling regulated by G proteins and to the closely related process of desensitization of hormone response. This review provides general information about the basic principles of G protein-regulated transmembrane signaling as well as about our contribution to the current progress in the field.

[Effect of Sulfakombin SPOFA on the dynamics of the extent of coccidiosis in small rabbit breeding operations]. / Ucinnost Sulfakombinu SPOFA na dynamiku extenzity kokcidiózy v drobných chovech králíku.

We determined the yearly changes in coccidiosis extensity applying the results of an examination of 2707 rabbits performed in the years 1981-1984. A field trial was conducted to study the efficiency of the Czechoslovak anticoccidic drug Sulfakombin Spofa administered to control coccidiosis in small rabbit breedings. We made the calculations to find out the optimum time of administration of sulphonamide substances. We discuss certain factors that influence in a decisive way the changes in coccidiosis extensity in rabbit breedings.

ATP but not adenosine inhibits nonquantal acetylcholine release at the mouse neuromuscular junction.

The postsynaptic membrane of the neuromuscular synapse treated with antiacetylcholinesterase is depolarized due to nonquantal release of acetylcholine (ACh) from the motor nerve ending. This can be demonstrated by the hyperpolarization produced by the application of curare (H-effect). ATP (1 x 10-5 M) decreased the magnitude of the H-effect from 5 to 1.5 mV. The membrane input resistance and the ACh sensitivity were unchanged, and so changes in these cannot explain the ATP effect. Adenosine alone was without effect on the nonquantal release. On the other hand, both ATP and adenosine depressed the frequency of spontaneous miniature endplate potentials, to 56% and 43% respectively. The protein kinase A inhibitor Rp-cAMP or the guanylyl cyclase inhibitor 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one did not affect the inhibitory influence of ATP on the H-effect, whereas staurosporine, an inhibitor of protein kinase C, completely abolished the action of ATP. Suramin, an ATP antagonist, enhanced the H-effect to 8.6 mV and, like staurosporine, prevented the inhibitory effect of ATP. ATP thus suppresses the nonquantal release via a direct action on presynaptic metabotropic P2 receptors coupled to protein kinase C, whilst adenosine exerts its action mainly by affecting the mechanisms underlying quantal release. These data, together with earlier evidence, show that nonquantal release of ACh can be modulated by several distinct regulatory pathways, in particular by endogenous substances which may or may not be present in the synaptic cleft at rest or during activity.