Fundamentals of power spectra of extracellular potentials produced by a skeletal muscle fibre of finite length. Part II: Effect of parameters altering with functional state

The reasons for dependence of the power spectra of extracellular potentials (EPs) produced by a skeletal muscle fibre of finite length, on parameters altering with functional state was analysed. The sensitivity of the EP power spectra to alterations in the parameters depends on the distance of the observation point from the fibre. At large distances the sensitivity can change with longitudinal position as well. The differences in the sensitivity are due to the changes in the inter-relations between the power spectra of the input signal (the first temporal derivative of the intracellular action potential) and of the impulse response (IR) of the fibre of finite length as a linear system of EP generation. It was shown that not only the parameters affecting the IR (propagation velocity of the waves of depolarisation), but also the parameters determining the input signal (intracellular action potential duration and after-potential) can affect the characteristic frequencies of the EP power spectra.     

Stimulation-evoked eye movements with and without the lateral rectus muscle pulley

Recent studies have suggested that extraocular muscle (EOM) pulleys, composed of collagen, elastin, and smooth muscle, are among the tissues surrounding the eye. High-resolution magnetic-resonance imaging appears to indicate that the pulleys serve to both constrain and alter the pulling paths of the EOMs. The active pulley hypothesis suggests that the orbital layer of the EOMs inserts on the pulley and serves to control it. Based on anatomical data, the active pulley hypothesis also suggests that the orbital layer does not rotate the eye within the orbit; this is done by the global layer of the muscle. However, no physiological data exist to confirm this hypothesis. Here we used stimulation-evoked eye movements in anesthetized monkeys and cats before and after destruction of the lateral rectus muscle pulley by removal of the lateral bony orbit and adjacent orbital tissue. The absence of these structures resulted in increased lateral, in the primate, and medial, in the cat, eye-movement amplitude and velocity. Vertical eye movements in the cat were not significantly affected. The results indicate that these increases, confined to horizontal eye-movement amplitude and velocity, may be attributed to passive properties within the orbit. In relation to the active pulley hypothesis, we could discern no clear impact (in terms of amplitude or velocity profile of the movements) of lateral eye exposure that could be directly attributable to the active lateral pulley system.     

Antichlamydial and antisperm antibodies in patients with chlamydial infections

PROBLEM: Establishing the correlation between antichlamydial antibodies (AchAbs) and antisperm antibodies (ASA) in patients with chlamydial infections. METHOD OF STUDY: ASA were studied in sera from patients (142 with genital, 57 with ocular chlamydial infections) and control group (n = 100) by gelatin and tray agglutination test (TAT), sperm immobilization test (SIT) and ELISA. AchAbs were revealed by ELISA. RESULTS: A significantly higher (P < 0.05) ASA incidence was noted in patients with genital infections as compared with controls and patients with ophthalmologic infection (P < 0.0001), but not between patients with ophthalmologic infection and controls (P > 0.05). A significant correlation was established between AchAbs and ASA for TAT (r = 0.8214, P = 0.0341), SIT (r = 0.797, P = 0.032) and ELISA (r = 0.8519, P = 0.0313) in patients with genital infections only. CONCLUSIONS: The genital Chlamydia infection may play a role in the induction of ASA. This is probably a result of the inflammatory process, but not of cross-reactivity between sperm and Chlamydia trachomatis antigens.     

Antidepressant‐like effect of anacardic acid in mice via the L‐arginine–nitric oxide–serotonergic system

Depression, a multifactorial neuronal disorder with high morbidity/mortality, is associated with psychological, psychosocial, hereditary, and environmental etiologies, where reactive species exert pathophysiological functions. Anacardic acid (AA), a natural compound obtained from cashew nut liquid, has several pharmacological activities, including antioxidant and anticonvulsant. The aim of the present study was to evaluate the antidepressant‐like effect of AA and the involvement of serotonergic, noradrenergic, and L‐arginine–nitric oxide (NO) in tail suspension and forced swim tests and, more so, to investigate its antioxidant effect in Saccharomyces cerevisiae and in male Swiss mice (n = 8). In order to identify the antidepressant mechanisms, AA (10, 25, or 50 mg/kg, p.o.) was given 30 min before clonidine (2‐adrenergic receptor agonist), L‐arginine (NO precursor), propranolol (β‐adrenergic receptor antagonist), and several other agonists or antagonists used. On the other hand, clonidine, noradrenoreceptor, noradrenaline, and L‐arginine were used to identify the antidepressant mechanisms. Results suggest that AA exerts antidepressant‐like activity, especially at higher doses, possibly by inhibiting serotonin and 5HT‐1A reuptake receptors and by inhibiting NO synthetase and guanylyl cyclase enzymes. Additionally, AA exhibited antioxidant effect in S. cerevisiae. This antioxidant capacity may be linked to its antidepressant‐like effect but does not interact with α‐ and β‐adrenoceptor receptors. In conclusion, AA may be used as a promising agent to treat depression, especially which arises from oxidative stress.     

Incidence and time trends of childhood lymphomas: findings from 14 Southern and Eastern European cancer registries and the Surveillance,Epidemiology and End Results,USA

Purpose

To describe epidemiologic patterns of childhood (0–14 years) lymphomas in the Southern and Eastern European (SEE) region in comparison with the Surveillance, Epidemiology and End Results (SEER), USA, and explore tentative discrepancies.

Methods

Childhood lymphomas were retrieved from 14 SEE registries (n = 4,702) and SEER (n = 4,416), diagnosed during 1990–2014; incidence rates were estimated and time trends were evaluated.

Results

Overall age-adjusted incidence rate was higher in SEE (16.9/10⁶) compared to SEER (13.6/10⁶), because of a higher incidence of Hodgkin (HL, 7.5/10⁶ vs. 5.1/10⁶) and Burkitt lymphoma (BL, 3.1 vs. 2.3/10⁶), whereas the incidence of non-Hodgkin lymphoma (NHL) was overall identical (5.9/10⁶ vs. 5.8/10⁶), albeit variable among SEE. Incidence increased with age, except for BL which peaked at 4 years; HL in SEE also showed an early male-specific peak at 4 years. The male preponderance was more pronounced for BL and attenuated with increasing age for HL. Increasing trends were noted in SEER for total lymphomas and NHL, and was marginal for HL, as contrasted to the decreasing HL and NHL trends generally observed in SEE registries, with the exception of increasing HL incidence in Portugal; of note, BL incidence trend followed a male-specific increasing trend in SEE.

Conclusions

Registry-based data reveal variable patterns and time trends of childhood lymphomas in SEE and SEER during the last decades, possibly reflecting diverse levels of socioeconomic development of the populations in the respective areas; optimization of registration process may allow further exploration of molecular characteristics of disease subtypes.

     

Docking‐based design and synthesis of galantamine–camphane hybrids as inhibitors of acetylcholinesterase

Galantamine (GAL) as an acetylcholinesterase inhibitor (AChEI) is among the main drugs approved for the treatment of Alzheimer's disease. It fits perfectly into acetylcholinesterase (AChE) binding gorge, but it is too short to fill it. The amyloid beta (Aβ) peptide binds in the peripheral anionic site (PAS) at the entrance of the binding gorge of AChE and initiates the formation of amyloid plaques. The blockade of PAS prevents from AChE‐induced Aβ aggregation. In this study, we describe the design of a series of galantamine–camphane hybrids as AChEIs. Camphane (CAM) is a bulky fragment that disposes well on the wide gorge entrance. The designed hybrids have linkers of different length. They were docked into AChE, and the highest scored compounds were synthesized and tested for AChE inhibitory activity. Some of the novel hybrids showed 191‐ and 369‐fold better inhibition than GAL. The CAM fragment of the best binders fits in the same region, proximal to PAS, where the Ω‐loop of Aβ binds to AChE. The hybrids cross blood–brain barrier by passive diffusion and are non‐neurotoxic at the inhibitory concentrations.     

Cytomegalovirus Infection Incidence and Risk Factors Across Diverse Hematopoietic Cell Transplantation Platforms Using a Standardized Monitoring and Treatment Approach: A Comprehensive Evaluation from a Single Institution

Human cytomegalovirus (CMV) infection and disease remains a significant cause of morbidity and mortality for hematopoietic cell transplantation (HCT) recipients. Disruption of or weak reconstitution of virus-specific cellular immune function, such as with certain HCT approaches, poses significant risk for CMV-related complications. The incidence of and risk factors for CMV infection and the nature of CMV disease were evaluated retrospectively among 356 consecutive HCT recipients transplanted at the National Institutes of Health using all graft sources, including bone marrow, peripheral blood stem cell (PBSC), and umbilical cord blood (UCB), and a range of in vivo and ex vivo approaches for graft-versus-host disease (GVHD) prophylaxis. The cumulative incidence of CMV infection was higher for CMV-seropositive recipients at 33%, regardless of donor CMV serostatus. Patients transplanted with CMV-seropositive donors had a significantly shorter duration of antiviral therapy. Among graft sources UCB was associated with the highest cumulative incidence of CMV infection at 65% and significantly longer treatment duration at a median of 36days, whereas PBSC HCT was associated with the lowest incidence at 26% and the shortest CMV treatment duration at a median of 21days. There were significant differences in the cumulative incidence of CMV infection by T cell manipulation strategy when systemic steroids were included as a risk-modifying event. Over one-third of CMV infections occurred in the setting of systemic steroid administration. CMV disease occurred in 5% of HCT recipients, with 70% of cases in the setting of treatment for GVHD. Although factors related to serostatus, graft source, and GVHD prophylaxis were associated with varied CMV infection incidence, unplanned post-HCT corticosteroid therapy contributed greatly to the incidence of both CMV infection and disease across HCT approaches, highlighting this post-HCT intervention as a key time to potentially tailor the approach to monitoring, preemptive therapy, and even prophylaxis.     

Placental teratoma--a case report.

A rare case of a mature placental teratoma in a 32-year-old woman is reported. We discuss the mechanism responsible for the development of this rare tumor in the placenta as well as the differential diagnostic difficulties encountered in fetus acardius amorphus, underlining the clinical significance of the exact diagnosis.