ADN-1184, a monoaminergic ligand with 5-HT_{6/7} receptor antagonist action, exhibits activity in animal models of anxiety

Behavioral and psychological symptoms of dementia (BPSD) include apathy, sleep problems, irritability, wandering, elation, agitation/aggression, and mood disorders such as depression and/or anxiety. Elderly patients are usually treated with second-generation antipsychotics; however, they present not enough efficacy against all symptoms observed. Hence, there still is an unmet need for novel pharmacotherapeutic agents targeted BPSD. A novel arylsulfonamide derivative ADN-1184 has been developed that possesses a preclinical profile of activity corresponding to criteria required for treatment of both psychosis and depressive symptoms of BPSD without exacerbating cognitive impairment or inducing motor disturbances. To broaden its pharmacological efficacy toward anxiety symptoms, its anxiolytic properties have been examined in common animal preclinical models in rats and mice. ADN-1184 significantly increased the number of entries into open arms measured in the elevated plus-maze test; however, it simultaneously increased parameters of exploratory activity. In the Vogel conflict drinking test, ADN-1184 dose-dependently and significantly increased the number of shocks accepted and the number of licks. Moreover, in mice, it also had specific anxiolytic-like activity in the four-plate test, and only negligible one at a specific mid-range dose measured in the spontaneous marble burying test. The obtained findings reveal that ADN-1184 displays anxiolytic-like activity in animal models of anxiety which employed punished stimuli. In its unusual combination of some anxiolytic action with already proven antipsychotic and antidepressant properties, and lack of any disruptive impact on learning and memory processes and motor coordination, ADN-1184 displays a profile that would be desired for a novel therapeutic for BPSD

Genetic variants in transforming growth factor-β gene (TGFB1) affect susceptibility to schizophrenia

Immense body of evidence indicates that dysfunction of immune system is implicated in the etiology of schizophrenia. The immune theory of schizophrenia is supported by alterations in cytokine profile in the brain and peripheral blood. Given the strong genetic background of schizophrenia, it might be assumed that aberrant production of cytokines might be the consequence of genetic factors. This study aimed at investigating the association between schizophrenia susceptibility and selected functional polymorphisms in genes encoding cytokines including: interleukin-2 (IL2 −330T>G, rs2069756), interleukin-6 (IL-6 −174G>C, rs1800795), interferon-γ (IFNG +874T>A, rs2430561) as well as for the first time transforming growth factor-β1 (TGFB1 +869T>C, rs1800470 and +916G>C, rs1800471). We recruited 151 subjects with schizophrenia and 279 controls. There was a significant difference in the genotype distribution and allelic frequency of the TGFB1 +869T>C between patients with schizophrenia and healthy controls (p < 0.05). The risk of schizophrenia was more than two-fold higher in carriers of T allele (CT+TT genotypes) than individuals with CC genotype. Given documented gender differences in incidence of schizophrenia, we conducted separate analyses of male and female participants. We have shown that the association was significant in females, while in males it reached a trend toward statistical significance. To the best of our knowledge, it is the first report showing the association between TGFB1 +869T>C polymorphism and schizophrenia

Study of a mechanism responsible for potential antidepressant activity of EMD 386088, a 5-HT_6 partial agonist in rats

It was shown that 5-HT(6) receptor agonists can exert pharmacological activity due to various modifications in monoamines’ level and metabolism activity in rats’ brain structures. This finding was correlated with antidepressant- or anxiolytic-like properties of these compounds. The study was designed to establish a possible mechanism of the antidepressant-like activity of the partial 5-HT(6) receptor agonist EMD386088 (5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole hydrochloride) in rats. The concentrations of monoamines (dopamine (DA), noradrenaline (NA), and serotonin (5-HT)) and the rate of their metabolism were measured ex vivo in the brain structures (hippocampus, nucleus accumbens, striatum) using high-performance liquid chromatography (HPLC). The rats were killed after the forced swim test (FST); the collected tissue samples were used to ex vivo experiments. The potency of EMD386088 to blockade dopamine transporter (DAT) was tested in a functional in vitro study. FST was used to assess the involvement of D(1)- and D(2)-like receptor subfamilies in antidepressant-like properties of EMD386088. Neurochemical data from ex vivo experiments showed that antiimmobility activity of EMD386088 may be connected with the activation of dopaminergic system, while neither noradrenergic nor serotonergic ones are involved in its effect. EMD386088 also possesses a significant affinity for DAT which may be a mechanism in the abovementioned effect. Behavioral data seem to confirm the importance of dopaminergic system activation in antidepressant-like activity of EMD386088, since this effect, observed in the FST, was abolished by the preferential D(1)- and D(2)-like receptor subfamily antagonists SCH23390 and sulpiride, respectively. Dopaminergic system is involved in antidepressant-like activity of EMD386088

Perinatal outcome in preterm premature rupture of membranes before 37 weeks of gestation

Objectives: The aim of this study was to assess the maternal and neonatal outcome in patients with preterm premature rupture of membranes between 22 to 37 weeks of gestation in comparison to preterm birth patients.  Material and methods: Group of PPROM patients consisted of 127 women, the control group counted 141 women who delivered prematurely. The control group was formed by matching patient with the same gestational age at delivery and neonatal birth weight to every woman from study group. In both groups speculum and ultrasound examinations were performed, microbiological swabs were taken. In unclear cases of PPROM tests detecting amniotic proteins, such as PAMG-1 or IGFBP-1, were performed. According to gestational age at delivery, neonates were divided into subgroups: extremely premature infants (&lt; 27 weeks 6 days), moderate premature infants (from 28 weeks 0 days to 33 weeks 6 days), late premature infants (from 34 weeks 0 days to 37 weeks 0 days).  Results: In the study group, median gestational age of delivery was 34 weeks 1 day and the same in control group — 34 weeks and 5 days (p &gt; 0.05). Parameters of inflammatory status were more often reported in the PPROM group than in the preterm birth group, even if they weren’t statistically significant (positive culture of cervical swab, increased leukocytosis, CRP above 5). The rate of neonate survival was similar in both groups (93.7% and 94.1%). Congenital infection was more often diagnosed in group of neonates from PPROM pregnancies than in neonates from control group; (36% and 21.2% respectively; p = 0.009).  Conclusions: Our research appears to be consistent with theory of inflammatory etiology of PPROM. Optimal management of infection in PPROM patients seems to be the most important in efforts to prolong pregnancy

Zastosowanie aromaterapii klinicznej w infekcjach intymnych kobiet

Application of natural essential oils of diverse therpeutical effects constitutes clinical aromatherapy. Among well-established biological and pharmacological activities of essential oils, their beneficial antibacterial and antifungal effects are reported from in vivo and in vitro studies on vaginal microbiome. At present, however, there is lack of reports on relation among microorganisms in vaginal smear, tested essential oils and physical and emotional health of female proband. Objective of the study was: (1) the influence analysis of applied aromatherapueitcal preparations on quantita-tive and qualitative profile of pathogenic vaginal microbiome and (2) the analysis of physical state and psychological well-being of proband woman. While gynaecological examination exhibited symptoms of bacterial and/or fungal infection of vulva and vagina, vaginal swab test taken from posterior vaginal fornix was used for microbiological examinations Within framework of performed aromatograms, identified facultative microorganisms of E. coli-var. and Candida sp. were subjectedto essential oils. Obtained results aided preparation of aromatherapeutic formulations of different applications: both topical (vaginal mucosa and cervical canal) and vaginal treatments. Final examinations certified effective antibacterial and antifungal influence of aromatherapeutic formulations, therein dedicated natural essential oils on imbalance of vaginal microbiome and on significant reduction of discomfort as well as psychical condition of proband woman.Zastosowanie naturalnych olejków eterycznych o różnorodnym działaniu terapeutycznym stanowi podstawę aromaterapii klinicznej będącej jednym z filarów współczesnej fitoterapii. Wśród udokumentowanej aktywności biologicznej i farmakologicznej naturalnych olejków eterycznych opisane jest również korzystne działanie przeciwbakteryjne i przeciwgrzybicze na mikrobiom pochwy w badaniach in vivo i in vitro. Brak jest jednak współczesnych doniesień wskazującychna związek pomiędzy drobnoustrojami obecnymi w wymazie pochwy, badanym naturalnym olejkiem eterycznym a stanem fizycznym i emocjonalnym probantki. Celem pracy była: (1) analiza wpływu zastosowanych preparatów aromaterapeutycznych na stan ilościowy i jakościowy patogennej flory pochwy jak i (2) analiza stanu fizycznego i samopoczucia psychicznego probantki. Podczas gdy badania ginekologiczne wykazały objawy infekcji bakteryjnej i/lub grzybiczej sromu i pochwy. Materiał wymazowy pobrany z tylnej części pochwy posłużył do szczegółowych badań mikrobiologicznych. W wymazach mikrobiologicznych przed i po zastosowaniu preparatów aromaterapeutycznych oznaczono rodzaj lub szczep patogennych bakterii, drożdżaków jak również wykonano badania ankietowe. Otrzymane wyniki posłużyły do przygotowania preparatów aromaterapeutycznych o różnej formie aplikacji: zarówno na skórę (śluzówkę pochwy i kanał szyjkimacicy) zewnętrznych narządów płciowych jak i dopochwowo. Końcowe badania zaświadczyły o skutecznym przeciwbakteryjnym i przeciwgrzybiczym wpływie preparatów aromaterapeutycznych, w tym dedykowanych naturalnych olejków eterycznych na zaburzenia biocenozy pochwy i na znacząca redukcję dyskomfortu jak i poprawę stanu psychicznego probantki