Presynaptic Adrenoceptors.

Presynaptic α2-adrenoceptors are localized on axon terminals of many noradrenergic and non-noradrenergic neurons in the peripheral and central nervous systems. Their activation by exogenous agonists leads to inhibition of the exocytotic release of noradrenaline and other transmitters from the neurons. Most often, the α2A-receptor subtype is involved in this inhibition. The chain of molecular events between receptor occupation and inhibition of the exocytotic release of transmitters has been determined. Physiologically released endogenous noradrenaline elicits retrograde autoinhibition of its own release. Some clonidine-like α2-receptor agonists have been used to treat hypertension. Dexmedetomidine is used for prolonged sedation in the intensive care; It also has a strong analgesic effect. The α2-receptor antagonist mirtazapine increases the noradrenaline concentration in the synaptic cleft by interrupting physiological autoinhibion of release. It belongs to the most effective antidepressive drugs. ß2-Adrenoceptors are also localized on axon terminals in the peripheral and central nervous systems. Their activation leads to enhanced transmitter release, however, they are not activated by endogenous adrenaline.

Cervical Pleuropulmonary Blastoma-like Tumor Associated With DICER1 and TP53 Mutations.

We describe a very unusual cervical tumor in a 12-yr-old patient with a clinical history indicative of DICER1 syndrome. Morphologic, immunohistochemical, and molecular genetic analysis together helped to diagnose this lesion as a cervical pleuropulmonary blastoma-like tumor, associated with TP53 and DICER1 mutations. The tumor displayed usual histologic features including mixtures of embryonal rhabdomyosarcoma, sarcomatous cartilage, compact blastema, primitive spindle cells and anaplasia, akin to type III pleuropulmonary blastoma, and trabecular and retiform patterns. In addition to expanding the phenotypic spectrum of DICER1 -associated conditions, we draw attention to genotype-phenotype correlations in DICER1 -associated tumors, particularly as they relate to the discovery of a heritable tumor predisposition syndrome.

Perinatal Prognosis of Pregnancies with Single Umbilical Artery in a Romanian Third-Level Unit.

Objectives: Single umbilical artery (SUA) is considered the most common abnormality of the umbilical artery. The objective of the study was to evaluate the perinatal prognosis of fetuses with SUA and to describe the associated malformations. The significance of the study is represented by examining whether our findings are in correlation with data already described.Methods: We performed a prospective cohort study on singleton pregnancies complicated with SUA. The study population was composed of women with singleton pregnancies who were examined at the Department of Obstetrics and Gynecology of the Târgu Mures County Emergency Clinical Hospital between 2012 and 2021.Results: The incidence of SUA in the study population was 0.48%. C-section was performed in 40 cases with SUA and in 5258 cases with no SUA (RR:1.56, P<0.05.) From the total number of 2249 premature deliveries, 23 newborns were diagnosed with SUA (RR:2.12, P<0.05.) From the total number of 869 deliveries with low birth weight (LBW) newborns, 13 were associated with SUA (RR: 3.12, P<0.05.) There were 206 pregnancies noted with antenatal fetal demise after 24 weeks of gestation, and only 2 of them were with SUA (RR:2.01, P>0.05.) Fetal and neonatal malformations were described in 290 cases, and 28 were associated with SUA (R:21.96, P<0.05.) In 57 of 85 cases (67.05%), we found iSUA, and 28 newborns (32.95%) had minor, major, or other associated pathologies. We found two cases of trisomy 18 and one case with trisomy 13 associated with SUA. Investigating the malformations associated with SUA, the most common were cardiac and great vessels malformations (12), followed by limb malformations (8), urogenital malformations (7), digestive tract malformations (7), central nervous system malformations (4), and in one case we found cleft palate.Conclusions: Perinatal prognosis regarding SUA is significantly poorer than in cases without this pathology. One-third of fetuses with SUA were associated with fetal anomalies. The most common pathologies associated with SUA were cardiovascular, limb, urogenital, and digestive system malformations. Our data are similar to those described in other studies; therefore, we conclude, we can implement the general recommendations in our region regarding counselling patients.

Primary angiosarcoma of the vulva: report of a case misdiagnosed as a benign tumor.

Primary vulvar angiosarcomas have a propensity for varied macroscopic and histologic appearance that initially may not suggest a vascular malignant neoplasm. Therefore, the rarity of the lesion and it's morphologic diversity may contribute to the high rate of misdiagnosis. We present the case of a 43-year old patient with a primary vulvar lesion, initially misdiagnosed as an angiofibroma. Microscopic examination of the recurrence together with immunohistochemical profile were in favor on a poorly differentiated angiosarcoma. Early diagnoses can improve prognoses in angiosarcomas and, in the case of recurrences, as in the present case, may lead to changes in therapy.

Pregnenolone does not interfere with the effects of cannabinoids on synaptic transmission in the cerebellum and the nucleus accumbens.

The steroid hormone pregnenolone attenuates several in vivo behavioural and somatic effects of the phytocannabinoid Δ9-tetrahydrocannabinol, and it was suggested that pregnenolone can protect the brain from cannabis intoxication. The primary neuronal cannabinoid action behind most of the behavioural and somatic effects of cannabinoids is presynaptic inhibition of synaptic transmission. Therefore, the hypothesis of the present study was that pregnenolone attenuates the inhibition of synaptic transmission elicited by cannabinoids. Brain slices containing the cerebellum or the nucleus accumbens were prepared from brains of mice and rats. Spontaneous and electrically evoked GABAergic inhibitory postsynaptic currents (sIPSCs and eIPSCs) and evoked glutamatergic excitatory postsynaptic currents (eEPSCs) were recorded in superfused brain slices with patch-clamp electrophysiological techniques. Pregnenolone (10-7M) did not affect the spontaneous GABAergic synaptic input (sIPSCs) to Purkinje cells in mouse cerebellar slices. The synthetic mixed CB1/CB2 receptor agonists JWH-210 (5×10-6M) and JWH-018 (5×10-6M) inhibited the spontaneous GABAergic synaptic input (sIPSCs) to Purkinje cells. This inhibition was not affected by pregnenolone (10-7M). Tetrahydrodeoxycorticosterone (THDOC; 10-7M), an in vivo metabolite of pregnenolone, also did not affect the inhibition of the GABAergic synaptic transmission by JWH-018. The depolarization of the Purkinje cells induced suppression of the GABAergic input to Purkinje cells; pregnenolone (10-7M) did not affect this endocannabinoid-mediated form of synaptic suppression. In rat nucleus accumbens slices, glutamatergic and GABAergic synaptic input to medium spiny neurons was activated by electrical stimulation of axons. Δ9-Tetrahydrocannabinol (2×10-5M), which is a partial agonist of both CB1 and CB2 receptors, suppressed the glutamatergic and GABAergic synaptic transmission in the rat nucleus accumbens. These suppressive effects of Δ9-tetrahydrocannabinol were not changed by pregnenolone (10-7M). The suppression of the GABAergic synaptic transmission by Δ9-tetrahydrocannabinol in the rat nucleus accumbens was also not affected by THDOC (10-7M). The results indicate that pregnenolone, a neurosteroid, does not affect GABAergic synaptic transmission. The inhibition of GABAergic and glutamatergic synaptic transmission elicited by synthetic, endogenous and phyto-cannabinoids is also not changed by pregnenolone. Therefore, it is unlikely that interference with cannabinoid-induced inhibition of synaptic transmission is the mechanism by which pregnenolone attenuates behavioural and somatic effects of Δ9-tetrahydrocannabinol in vivo.

Trends in outcomes of very preterm infants in Romania: A tale of three cities.

BACKGROUND: Although survival of preterm infants has improved, prematurity remains the second most frequent cause of death before 5 years of age in Romania. Data on the changing mortality of Romanian preterm infants born before 29 weeks of gestation have not been available. METHODS: Outcomes of infants of gestational age 25-28 weeks born in 2007-2010 (n = 247) were compared with those born in 2011-2014 (n = 235). Data were analyzed from three tertiary neonatal intensive care centers. Mortality rates and major morbidities were compared between these two epochs. RESULTS: Infants in the later epoch were more likely to have been born by cesarean section and had higher 1 and 5 min Apgar scores. Mortality rate decreased significantly with increasing gestational age at birth. Between the two epochs, the in-hospital mortality rate decreased from 65.6% to 29.4% (P < 0.001); death in the first 48 h decreased from 30.0% to 8.5% (P < 0.001); and prevalence of severe intraventricular hemorrhage decreased from 52.2% to 11.9% (P < 0.001). There were significant increases in the rates of necrotizing enterocolitis and bronchopulmonary dysplasia among survivors but no change in the rate of retinopathy of prematurity. The rate of antenatal corticosteroid use did not change and was only 47% in the more recent epoch (2011-2014). CONCLUSIONS: Overall mortality is decreasing, and infants admitted in the later epoch had substantially different rates of mortality and several serious morbidities. The low rate of antenatal corticosteroid use provides an opportunity for further reductions in mortality and morbidity among very preterm infants born in Romania.

Radical Trachelectomy Performed During Pregnancy: A Review of the Literature.

OBJECTIVE: Cervical cancer is one of the most frequent malignant diseases diagnosed during pregnancy. Abdominal or vaginal radical trachelectomies are fertility-preserving alternatives to radical hysterectomy for young women with early-stage cervical cancer that can be performed during ongoing pregnancy. METHODS: A literature review of articles on this subject was conducted through a Medline search for articles published in English or French. RESULTS: At this moment, 21 cervical cancer patients, including ours (4 stage IA2, 16 IB1, and 1 IB2) who underwent radical trachelectomy during pregnancy have been reported. Of these, 10 were performed by vaginal route and 11 were abdominal radical trachelectomies. CONCLUSIONS: Radical trachelectomy could be offered as an option for pregnant patients with early invasive cervical cancer. It may help women avoid the triple losses of a desired pregnancy, fertility, and motherhood.

Abdominal radical trachelectomy: a Romanian series.

OBJECTIVE: Abdominal radical trachelectomy (ART) is one of the fertility-sparing procedures in women with early-stage cervical cancer. The published results of ART, in comparison with vaginal radical trachelectomy, so far are limited. MATERIALS AND METHODS: This retrospective study comprises all cases of female patients referred to ART with early-stage cervical cancer from 2 gynecologic oncology centers in Romania. RESULTS: A total of 29 women were referred for ART, but subsequently, fertility could not be preserved in 3 of them. Eleven women had stage IA2 disease (42.3%), 14 (53.8%) women had stage IB1 disease, and 1 (3.8%) woman had stage IB2 disease. Histologic subtypes were 15 (57.6%) squamous, 8 (30.7%) adenocarcinoma, and 3 (11.5%) adenosquamous. There were no major intraoperative complications in both hospitals. Early postoperative complications were mainly related to the type C parametrectomy-bladder dysfunction for more than 7 days (8 [30.7%] women) and prolonged constipation (6 [23.0%] women). Other complications consisted in symptomatic lymphocele in 2 (7.6%) patients, which were drained. Median follow-up time was 20 months (range, 4-43 months). Up to the present time, there has been 1 (3.8%) recurrence in our series. Most patients did not experience late postoperative complications. Three (11.5%) women are amenorrheic, and 1 (3.8%) woman developed a cervical stenosis. Of the 23 women who have normal menstruation and maintained their fertility, a total of 7 (30.4%) women have attempted pregnancy, and 3 (42.8%) of them achieved pregnancy spontaneously. These pregnancies ended in 2 first trimester miscarriages and 1 live birth at term by cesarean delivery. CONCLUSIONS: Our results demonstrate that ART preserves fertility and maintains excellent oncological outcomes with low complication rates.

Mortality and morbidity of very preterm infants in Romania: how are we doing?

BACKGROUND: Birth before 28 weeks of gestation is associated with high mortality and morbidity. The purpose of this study was to examine characteristics associated with in-hospital mortality and morbidity among extremely low-birthweight neonates admitted to three tertiary care centers in Romania. METHODS: The study was conducted in three Romanian hospitals with level-III neonatal intensive care units. We studied singleton live births at the established Romanian limit of viability (i.e., 25-28 weeks' gestational age) born between January 2007 and December 2010 (n = 227). Infants born in non-level-III facilities transferred to these three centers were included in our study (n = 39). Descriptive and multivariate statistical analyses were used to describe the population and examine outcomes and risk factors. RESULTS: During the study period, 62 neonates (27.3%) were delivered at 25 weeks, 56 (24.7%) were delivered at 26 weeks, 56 (24.7%) at 27 weeks, and 53 (23.3%) at 28 weeks. Overall in-hospital mortality was 65% (from 85% at 25 weeks to 35% at 28 weeks). The rates for major morbidities were necrotizing enterocolitis 8.8%, bronchopulmonary dysplasia 12.5%, and retinopathy of prematurity (stage higher than 2) 26.2%. CONCLUSIONS: During 2007-2010, in-hospital survival of infants admitted to three neonatal intensive care units in Romania was 35% and ranged from 14% at 25 weeks to 64% at 28 weeks.

When a Chorangioma Becomes a Burden in Fetal Survival: A Reported Case with an Updated Literature Review.

Chorangioma is a rare non-trophoblastic benign vascular neoplasm originating from the primitive chorionic mesenchyme. Usually asymptomatic, it affects approximately 1% of female fetuses. We present the case of a giant placental chorangioma (GPC) in a preterm male pregnancy coexisting with a maternal neuroendocrine carcinoma. A 30-week primigravida was admitted to the Obstetrics and Gynecology Clinic of the Targu-Mures Emergency Clinical Hospital, with abdominal discomfort, and an emergency C-section was performed for fetal congestive heart failure. Medical history revealed an advanced-stage rectal neuroendocrine carcinoma. At 20th gestational week, a well-vascularized placental mass was diagnosed. A 1500g premature male fetus was delivered. Histopathologically, the placental mass revealed an unencapsulated but well-circumscribed tumor with lobular architecture composed of congested vascular capillaries and thin-walled vessels. Diagnosis of giant placental chorangioma (GPC) was rendered. GPC is a challenging condition typically occurring in hypertensive or diabetic primigravidas with female fetuses. Antenatal management is suggested at an early stage for a desirable perinatal outcome.

Intraplaque Neovascularization, CD68+ and iNOS2+ Macrophage Infiltrate Intensity Are Associated with Atherothrombosis and Intraplaque Hemorrhage in Severe Carotid Atherosclerosis.

BACKGROUND: Atherosclerosis is a progressive disease that results from endothelial dysfunction, inflammatory arterial wall disorder and the formation of the atheromatous plaque. This results in carotid artery stenosis and is responsible for atherothrombotic stroke and ischemic injury. Low-grade plaque inflammation determines biological stability and lesion progression. METHODS: Sixty-seven cases with active perilesional inflammatory cell infiltrate were selected from a larger cohort of patients undergoing carotid endarterectomy. CD68+, iNOS2+ and Arg1+ macrophages and CD31+ endothelial cells were quantified around the atheroma lipid core using digital morphometry, and expression levels were correlated with determinants of instability: ulceration, thrombosis, plaque hemorrhage, calcification patterns and neovessel formation. RESULTS: Patients with intraplaque hemorrhage had greater CD68+ macrophage infiltration (p = 0.003). In 12 cases where iNOS2 predominated over Arg1 positivity, the occurrence of atherothrombotic events was significantly more frequent (p = 0.046). CD31 expression, representing neovessel formation, correlated positively with atherothrombosis (p = 0.020). CONCLUSIONS: Intraplaque hemorrhage is often described against the background of an intense inflammatory cell infiltrate. Atherothrombosis is associated with the presence of neovessels and pro-inflammatory macrophages expressing iNOS2. Modulating macrophage polarization may be a successful therapeutic approach to prevent plaque destabilization.

Management of recurrent vulvovaginal candidosis: Narrative review of the literature and European expert panel opinion.

Recurrent vulvovaginal candidosis (RVVC) is a chronic, difficult to treat vaginal infection, caused by Candida species, which affects women of all ages and ethnic and social background. A long-term prophylactic maintenance regimen with antifungals is often necessary. In most clinical practice guidelines, oral fluconazole is recommended as the first-line treatment. Although clinical resistance to antifungal agents remains rare, overexposure to azoles may increase the development of fluconazole-resistant C. albicans strains. In addition, non-albicans Candida species are frequently dose-dependent susceptible or resistant to fluconazole and other azoles, and their prevalence is rising. Available therapeutic options to treat such fluconazole-resistant C. albicans and low susceptibility non-albicans strains are limited. Ten experts from different European countries discussed problematic issues of current RVVC diagnosis and treatment in two audiotaped online sessions and two electronic follow-up rounds. A total of 340 statements were transcribed, summarized, and compared with published evidence. The profile of patients with RVVC, their care pathways, current therapeutic needs, and potential value of novel drugs were addressed. Correct diagnosis, right treatment choice, and patient education to obtain adherence to therapy regimens are crucial for successful RVVC treatment. As therapeutic options are limited, innovative strategies are required. Well- tolerated and effective new drugs with an optimized mechanism of action are desirable and are discussed. Research into the impact of RVVC and treatments on health-related quality of life and sex life is also needed.

Oxidative stress and peripartum outcomes (Review).

Pregnancy, labor and childbirth are accompanied by excessive oxidative aggression. The excessive formation of free radicals [reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorine reactive species (CRS)] causes cellular oxidative damage, which can be scavenged by enzymatic or non-enzymatic antioxidants in normal healthy pregnancy, physiological labor and delivery without any complications. An imbalance between the pro-oxidant and antioxidant factors may lead to oxidative stress, which contributes to the development of many diseases. This oxidative aggression can be a precursor for pathologies in the pregnant woman including eclampsia, miscarriage, preterm labor, and intrauterine growth retardation; in the offspring it may lead to bronchopulmonary dysplasia/chronic lung disease, necrotizing enterocolitis, retinopathy of prematurity, and periventricular leukomalacia. This review summarizes the studies conducted to identify the mechanisms of oxidative stress and the effect of cell membrane oxidation, the mechanisms that are behind oxidative stress-related diseases, and also those studies which have demonstrated the effect of antioxidants in preventing diseases or diminishing the effects of oxidative stress in the body, in obstetrics and neonatology.

Potentiation of the glutamatergic synaptic input to rat locus coeruleus neurons by P2X7 receptors.

Locus coeruleus (LC) neurons in a rat brain slice preparation were superfused with a Mg(2+)-free and bicuculline-containing external medium. Under these conditions, glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) were recorded by means of the whole-cell patch-clamp method. ATP, as well as its structural analogue 2-methylthio ATP (2-MeSATP), both caused transient inward currents, which were outlasted by an increase in the frequency but not the amplitude of the sEPSCs. PPADS, but not suramin or reactive blue 2 counteracted both effects of 2-MeSATP. By contrast, α,ß-methylene ATP (α,ß-meATP), UTP and BzATP did not cause an inward current response. Of these latter agonists, only BzATP slightly facilitated the sEPSC amplitude and strongly potentiated its frequency. PPADS and Brilliant Blue G, as well as fluorocitric acid and aminoadipic acid prevented the activity of BzATP. Furthermore, BzATP caused a similar facilitation of the miniature (m)EPSC (recorded in the presence of tetrodotoxin) and sEPSC frequencies (recorded in its absence). Eventually, capsaicin augmented the frequency of the sEPSCs in a capsazepine-, but not PPADS-antagonizable, manner. In conclusion, the stimulation of astrocytic P2X7 receptors appears to lead to the outflow of a signalling molecule, which presynaptically increases the spontaneous release of glutamate onto LC neurons from their afferent fibre tracts. It is suggested, that the two algogenic compounds ATP and capsaicin utilise separate receptor systems to potentiate the release of glutamate and in consequence to increase the excitability of LC neurons.

Genetic dissection of alpha2-adrenoceptor functions in adrenergic versus nonadrenergic cells.

Alpha(2)-adrenoceptors mediate diverse functions of the sympathetic system and are targets for the treatment of cardiovascular disease, depression, pain, glaucoma, and sympathetic activation during opioid withdrawal. To determine whether alpha(2)-adrenoceptors on adrenergic neurons or alpha(2)-adrenoceptors on nonadrenergic neurons mediate the physiological and pharmacological responses of alpha(2)-agonists, we used the dopamine beta-hydroxylase (Dbh) promoter to drive expression of alpha(2A)-adrenoceptors exclusively in noradrenergic and adrenergic cells of transgenic mice. Dbh-alpha(2A) transgenic mice were crossed with double knockout mice lacking both alpha(2A)- and alpha(2C)-receptors to generate lines with selective expression of alpha(2A)-autoreceptors in adrenergic cells. These mice were subjected to a comprehensive phenotype analysis and compared with wild-type mice, which express alpha(2A)- and alpha(2C)-receptors in both adrenergic and nonadrenergic cells, and alpha(2A)/alpha(2C) double-knockout mice, which do not express these receptors in any cell type. We were surprised to find that only a few functions previously ascribed to alpha(2)-adrenoceptors were mediated by receptors on adrenergic neurons, including feedback inhibition of norepinephrine release from sympathetic nerves and spontaneous locomotor activity. Other agonist effects, including analgesia, hypothermia, sedation, and anesthetic-sparing, were mediated by alpha(2)-receptors in nonadrenergic cells. In dopamine beta-hydroxylase knockout mice lacking norepinephrine, the alpha(2)-agonist medetomidine still induced a loss of the righting reflex, confirming that the sedative effect of alpha(2)-adrenoceptor stimulation is not mediated via autoreceptor-mediated inhibition of norepinephrine release. The present study paves the way for a revision of the current view of the alpha(2)-adrenergic receptors, and it provides important new considerations for future drug development.

Depolarizing GABAergic synaptic input triggers endocannabinoid-mediated retrograde synaptic signaling.

Endocannabinoids released by postsynaptic neurons inhibit neurotransmitter release from presynaptic axon terminals. One typical stimulus of endocannabinoid production is an increase of calcium concentration in postsynaptic neurons. The aim of the present study was to clarify whether depolarizing GABAergic synaptic input, by increasing calcium concentration in postsynaptic neurons, can trigger endocannabinoid production. Spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were recorded in Purkinje cells in mouse cerebellar slices with patch-clamp pipettes containing 151 mM chloride (a usual recording mode). sIPSCs were depolarizing inward currents under this condition. Combined electrophysiological and fluorometric calcium imaging experiments indicated that sIPSCs frequently triggered calcium spikes. After the calcium spikes, a short-term suppression of sIPSCs occurred. This suppression was prevented by the CB(1) cannabinoid receptor antagonist rimonabant and the diacylglycerol lipase inhibitor orlistat, but not changed by URB597, an inhibitor of anandamide degradation. It is, therefore, likely that CB(1) receptors and 2-arachidonoylglycerol were involved. For testing the physiological significance of the above observation, we carried out experiments on brains of 3- to 5-day-old mice. The gramicidin-induced perforated patch-clamp mode was used for preserving the physiological intracellular chloride concentration of the neurons. Depolarizing GABAergic sIPSCs occurred under this condition, but at a very low rate. Rimonabant did not change the frequency of these sIPSCs, arguing against the persistence of an endocannabinoid tone. The results point to a new kind of trigger of endocannabinoid production: depolarizing GABAergic synaptic input can elicit endocannabinoid production in postsynaptic neurons by activating calcium channels. The produced endocannabinoid suppresses GABA release from presynaptic axon terminals.

Adolescent smoking and the social capital of local communities in three counties in Romania.

OBJECTIVE: To identify the effect of social capital on adolescent smoking. METHOD: A stratified random sample of 1313 7th and 8th grade students from three counties in Transylvania, Romania, completed a self-administered questionnaire on smoking-related knowledge, attitudes and behaviours. The impact of social capital was measured (personal and community activities, school achievements and smoking-related knowledge). Multivariate multinomial logistic regression models were used to measure the association between social participation and smoking. RESULTS: Experimenting with smoking was mostly related to knowledge about smoking, academic performance and second-hand tobacco smoke exposure at home. The strongest risk factor of adolescent smoking was the smoking behaviour of classmates: those who reported a significant proportion of smokers among their classmates were nine times more likely to smoke themselves than in other cases (adjusted odds ratio [aOR]: 9.05). Those who considered smoking to be harmless were 4 times more likely to be smokers than those who considered this behaviour to be dangerous (aOR: 4.28). Poor academic results increased adolescents' smoking (aOR: 3.22 and 2.66). The odds were significantly higher for smoking, if they had an active social life (aOR: 2.54). Regular church attendance proved to be a protective factor (aOR: 0.45). CONCLUSIONS: Several social capital factors can play a role in adolescent smoking. The organization and the development of community activities aimed at prevention must strengthen the factors related to the community's social capital to reduce the likelihood of teenage smoking.

The role of TGF-ß1 869 T > C and PPAR γ2 34 C > G polymorphisms, fat mass, and anthropometric characteristics in predicting childhood obesity at birth: A cross-sectional study according the parental characteristics and newborn's risk for child obesity (the newborns obesity's risk) NOR study.

This study proposed to establish a correlation between the risk score for child obesity and anthropometric, genetic, and bioimpedance characteristics in mothers and newborns, and to assess the discriminant ability for anthropometric parameters to classify over-fatness (defined by bioimpedance body fatness %) in pregnant women.We performed a cross-sectional study on 388 couples (mother and father) and their newborns admitted in a Tertiary Hospital from Romania. The measured parameters for mothers and their newborns were risk percentage for child obesity, anthropometric characteristics (mid-upper arm circumference [MUAC], tricipital skinfold thickness [TST] of mother and newborn), genetic polymorphisms (human peroxisome proliferator-activated receptor γ [PPARγ2] 34 C > G and transforming growth factor-beta 1 [TGF-ß1] 869 T > C gene polymorphisms in both mothers and newborns), and mother's bioimpedance characteristics (fat mass [FM] %).The obesity risk score according to standard predictable Northern Finland Birth Cohort equation was in our study 4.07%. We found a monotone positive significant correlation between the newborn's risk of childhood obesity and the mother's TST (P = 0.01), as well as a tendency toward statistical significance concerning correlation with mother's MUAC (P = 0.053), without any correlations with the mothers' bioimpedance parameters and also a positive correlation between the newborn's risk of childhood obesity and the newborn's anthropometrical characteristics like body mass index (BMI), MUAC, and TST (P < 0.001). We observed that the calculated newborn's risk percentage for child obesity was greater for the variant allele of the TGF-ß1 869 T > C polymorphism and also for the wild-type C allele of the PPARγ2 34 C > G gene polymorphism. Our study indicated that the best predictors for over-fatness are BMI and MUAC (P = 0.01 < 0.02 and P = 0.019 < 0.02, respectively).

Imidazoline antihypertensive drugs: a critical review on their mechanism of action.

It was long thought that the prototypical centrally acting antihypertensive drug clonidine lowers sympathetic tone by activating alpha(2)-adrenoceptors in the brain stem. Supported by the development of two new centrally acting drugs, rilmenidine and moxonidine, the imidazoline hypothesis evolved recently. It assumes the existence of a new group of receptors, the imidazoline receptors, and attributes the sympathoinhibition to activation of I(1) imidazoline receptors in the medulla oblongata. This review analyzes the mechanism of action of clonidine-like drugs, with special attention given to the imidazoline hypothesis. Two conclusions are drawn. The first is that the arguments against the imidazoline hypothesis outweigh the observations that support it and that the sympathoinhibitory effects of clonidine-like drugs are best explained by activation of alpha(2)-adrenoceptors. The second conclusion is that this class of drugs lowers sympathetic tone not only by a primary action in cardiovascular regulatory centres in the medulla oblongata. Peripheral presynaptic inhibition of transmitter release from postganglionic sympathetic neurons contributes to the overall sympathoinhibition.

Search for an endogenous cannabinoid-mediated effect in the sympathetic nervous system.

Activation of CB(1) cannabinoid receptors by exogenous agonists causes presynaptic inhibition of neurotransmitter release from axon terminals. In the central nervous system, presynaptic CB(1) receptors can also be activated by endogenous cannabinoids (endocannabinoids) released from postsynaptic neurons. Except in the vas deferens, there is no indication of endocannabinoid-mediated presynaptic inhibition in the sympathetic nervous system. The aim of the present study was to search for such inhibition in pithed rats. Artificial sympathetic tone was established by continuous electrical stimulation of preganglionic sympathetic axons. The CB(1) cannabinoid receptor antagonist rimonabant (0.5 and 2 mg kg(-1) i.v.) did not change blood pressure, heart rate or plasma noradrenaline concentration. Since activation of Galpha(q/11) protein-coupled receptors enhances endocannabinoid synthesis in the central nervous system, we attempted to stimulate endocannabinoid production by infusion of arginine vasopressin and phenylephrine (both activate Galpha(q/11) protein-coupled receptors). Rimonabant (2 mg kg(-1) i.v.) did not change blood pressure, heart rate or plasma noradrenaline concentration during infusion of phenylephrine or vasopressin. In the final series of experiments we verified that an exogenous cannabinoid agonist produces sympathoinhibition. The synthetic CB(1)/CB(2) receptor agonist WIN55212-2 (0.1 and 1 mg kg(-1) i.v.) markedly lowered blood pressure and plasma noradrenaline concentration in pithed rats with electrically stimulated sympathetic outflow. In contrast, in pithed rats with a pressor infusion of noradrenaline, WIN55212-2 did not change blood pressure or heart rate. The results verify that activation of peripheral presynaptic CB(1) receptors inhibits noradrenaline release from sympathetic nerve terminals. The lack of effect of the CB(1) receptor antagonist rimonabant indicates that, even under conditions favouring endocannabinoid synthesis, endocannabinoid-mediated presynaptic inhibition is not operating in the sympathetic nervous system of the pithed rat.