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Abstract: The importance of Ca2+-signaling for many subcellular processes is well established in higher eukaryotes, whereas information about protozoa is restricted. Recent genome analyses have stimulated such work also with Alveolates, such as ciliates (Paramecium, Tetrahymena) and their pathogenic close relatives, the Apicomplexa (Plasmodium, Toxoplasma). Here we compare Ca2+ signaling in the two closely related groups. Acidic Ca2+ stores have been characterized in detail in Apicomplexa, but hardly in ciliates. Two-pore channels engaged in Ca2+-release from acidic stores in higher eukaryotes have not been stingently characterized in either group. Both groups are endowed with plasma membrane- and endoplasmic reticulum-type Ca2+-ATPases (PMCA, SERCA), respectively. Only recently was it possible to identify in Paramecium a number of homologs of ryanodine and inositol 1,3,4-trisphosphate receptors (RyR, IP3R) and to localize them to widely different organelles participating in vesicle trafficking. For Apicomplexa, physiological experiments suggest the presence of related channels although their identity remains elusive. In Paramecium, IP3Rs are constitutively active in the contractile vacuole complex; RyR-related channels in alveolar sacs are activated during exocytosis stimulation, whereas in the parasites the homologous structure (inner membrane complex) may no longer function as a Ca2+ store. Scrutinized comparison of the two closely related protozoan phyla may stimulate further work and elucidate adaptation to parasitic life. See also “Conclusions” section. [Copyright &y& Elsevier]

Abstract: The authors show the results related to the longitudinal study of a six-months pregnant, depressive woman until four months postpartum. She has accepted a short psychoanalytical psychotherapy. The originality of that study is triple: longitudinal studies during that perinatal period are seldom if we consider previous researches reviewed; psychological evaluation at eight-months time interval using multidimensional clinical methodology based on behavioural and psychoanalytical frame of reference has never been undertaken. Indeed, we simultaneously have used therapy data, scales and questionnaires related to health psychology to appreciate behavioural changes (SF 36 quality of life scale, Carver''s Brief Cope, General Health Questionnaire 12, EPDS perinatal depression scale), and a projective technique (Rorschach test) to evaluate intrapsychic changes; to give the reader the opportunity to account precisely for changes related to psychoanalytical psychotherapy. Results clearly shows usefulness of that type of psychotherapy from a preventive perspective to face perinatal depression. Indeed, psychoanalytic following allows to reduce significantly perinatal depressive state to improve adaptative coping strategies and life quality and finally to favour intrapsychic reorganization. That last point was clearly demonstrated by the comparison of data at time 1 and 2 of research. Future researches are suggested to give more consistence to the conclusions related to that single case study. [Copyright &y& Elsevier]

We investigate the structure and the optical properties of hexagonally ordered rings of zinc oxide and zinc cadmium oxide, which were produced by nano-porous membranes on silicon substrates. These ‘donuts’ have an average diameter of 300 nm, they are about 100 nm high and are 350 nm apart from each other. The influence of annealing at different temperatures was studied by scanning electron microscopy for structural quality and by photoluminescence spectroscopy for optical quality. Samples with different ratios of zinc and cadmium were investigated. Energy-dispersive X-ray spectroscopy proved the assumed composition of the ‘donuts’. [Copyright &y& Elsevier]

Background: Antenatal pulmonary inflammation is associated with reduced risk for respiratory distress syndrome but with an increased risk for bronchopulmonary dysplasia (BPD) with impaired alveogenesis. Objective: We hypothesized that fetal systemic inflammation induced by intravenous (IV) lipopolysaccharide (LPS) would affect lung development in utero. Study Design: Twenty-one fetal sheep were instrumented (107 days gestational age). Control fetuses received saline (N = 12) and 9 in the study group received 100 ng of LPS IV 3 days after surgery. Animals were assessed for lung maturation and structure after 3 (N = 5) and 7 (N = 4) days. Results: Interleukin-6 concentration increased in the bronchoalveolar lavage more than 40-fold 3 days after LPS IV. Processing of pro-surfactant protein (SP)-B to mature SP-B and increased SP-B concentrations were shown 7 days after LPS IV. Deposition of elastin fibers at sites of septation was disturbed within 3 days after LPS IV. Conclusion: Lung maturation and disturbed lung structure occurred after short-term exposure to fetal inflammation and suggests new targeted therapies for BPD. [Copyright &y& Elsevier]

Abstract: The 5-HT3 receptor is a pentameric ligand-gated cation channel which is found in the central and peripheral nervous system and on extraneuronal locations like lymphocytes, monocytes and fetal tissue. Five monomer subtypes, the 5-HT3A–E subunits, have been identified which show differences in the amino-terminal and the transmembrane region. The functional relevance of different receptor compositions is not yet clarified. 5-HT3 receptors are located predominantly in CNS regions that are involved in the integration of the vomiting reflex, pain processing, the reward system and anxiety control. The preferential localization on nerve endings is consistent with a physiological role of 5-HT3 receptors in the control of neurotransmitter release such as dopamine, cholecystokinin, glutamate, acetylcholine, GABA, substance P, or serotonin itself. 5-HT3-receptor agonists cause unpleasant effects like nausea and anxiety, and no clinical use has been considered. In contrast, the introduction of 5-HT3-receptor antagonists for chemotherapy-induced vomiting was extremely successful. After development of other gastrointestinal indications like postoperative vomiting and diarrhea-predominant irritable bowel syndrome recent research focuses on rheumatological indications such as fibromyalgia, rheumatoid arthritis and tendinopathies. Positive effects have also been observed for pain syndromes such as chronic neuropathic pain and migraine. These effects seem to be related to substance P-mediated inflammation and hyperalgesia. Furthermore, antiinflammatory and immunomodulatory properties have been observed for 5-HT3-receptor antagonists which might explain promising findings in systemic sclerosis and other immunological conditions. For all of these innovative indications the optimal dosing schedule is a crucial issue, since a bell-shaped dose–response curve has been observed repeatedly for 5-HT3-receptor antagonists, particularly in CNS effects. [Copyright &y& Elsevier]

Abstract: Background: The aim of this study was to demonstrate noninferiority of everolimus with reduced cyclosporine (CsA) vs mycophenolate mofetil (MMF) with reduced CsA in improving renal function. Methods: In this 1-year randomized, open-label, noninferiority study in maintenance heart transplant recipients with impaired renal function 70 patients received everolimus (n = 36) or MMF (n = 34) in combination with reduced CsA. The planned sample size was not reached as the study was prematurely discontinued due to slow recruitment. Results: Noninferiority of the everolimus regimen could not be shown: In the total population MMF seemed to be favorable on renal function assessed by serum creatinine and filtration rates, but not in the subset of patients who reached the intended reduced CsA level. Incidence rates of rejection episodes were significantly higher under MMF at month 6 (P = .0332). Conclusions: Overall, the results of this trial using reduced CsA in combination with either everolimus or MMF show that there is evidence to reduce the CsA level when everolimus is given concomitantly and that the benefit of MMF with reduced CsA levels is limited due to insufficient immunosuppression. [Copyright &y& Elsevier]

Abstract: Background: The narrow therapeutic window of cyclosporine (CsA) requires close therapeutic drug monitoring (TDM). While C2-TDM has been established after renal and liver transplantations, clinical experience is limited for patients after de novo heart transplantation (HTX). Patients and Methods: In a retrospective study, we investigated 40 patients undergoing HTX; 34 patients received induction therapy using antithymocyte globulin (ATG Mérieux). Immunosuppression was administered with CsA (Sandimmun-Optoral), with dosages adjusted according to C2 levels (800–1100 ng/mL during the first 6 months and reduced to 400–600 ng/mL from the beginning of the first year). At different times TI (months 1–3). TII (months 12–14) TIII (months 24–26), and TIV (months 34–36), we obtained measures of acute cellular rejections (ARs), cytomegalovirus (CMV) infections, creatinine, and safety laboratory parameters. Results: The cumulative survival was 95% after 1 year, and 88% after 3.8 years. Eight ARs were diagnosed at a mean of 7.6 months after HTX in 7 patients. Twenty-four CMV infections/reactivations were verified. In 10 cases, treatment was started because of clinical symptoms. The mean creatinine values significantly rose in the early postoperative phase (TI: 1.23 ± 0.47 mg/dL, TII: 1.49 ± 0.41 mg/dL; P < .0001). Thereafter the creatinine values declined; however, this was not statistically significant (TIII: 1.38 ± 0.57 mg/dL, TIV: 1.15 ± 0.30 mg/dL). All other safety parameters showed no significant changes. Conclusions: C2 allows individualization of immunosuppression with reduced CsA toxicity, but without loss in safety among de novo patients after HTX. We obtained freedom from severe AR, a low number of CMV infections, and excellent patient survival. [Copyright &y& Elsevier]

Abstract: Mycophenolic acid (MPA) is an effective immunosuppressive treatment for renal transplant recipients, but its effective use and best practice are not established in cardiac transplantation. This multicenter, single-blind, randomized, parallel group clinical trial prospectively evaluated the therapeutic equivalence of enteric-coated mycophenolate-sodium (EC-MPS) versus mycophenolate mofetil (MMF) in combination with cyclosporine (CyA) and steroids as determined by the primary objective of treatment efficacy during the first 6 months of treatment in 154 de novo heart transplant recipients. Both groups received equivalent doses of MPA, either 720 mg b.i.d EC-MPS or 1000 mg b.i.d MMF. EC-MPS showed a comparable efficacy and safety profile compared with MMF with significantly less dose reduction. Treatment failure occurred in 57.7% and 60.5% with EC-MPS and MMF, respectively, EC-MPS was therapeutically equivalent to MMF in cardiac transplantation. [Copyright &y& Elsevier]