Responses of bronchial C-fiber afferents of the rabbit to changes in lung compliance

Rapidly adapting receptors (RAR) in the lung are stimulated when the lung compliance is reduced. The present investigation was undertaken to determine whether bronchial C-fibers are also activated when lung compliance is decreased since both RAR and bronchial C-fibers are influenced by extra-vascular fluid in the airways. Action potentials (AP) were recorded from bronchial C, pulmonary C, RAR and slowly adapting receptor (SAR) afferents in the cervical vagus in open chest New Zealand White rabbits ventilated at a constant rate and tidal volume. AP were recorded during (a) positive end-expiratory pressure (PEEP) of 2-3 cmH2O (control), (b) zero end-expiratory pressure (ZEEP), (c) negative end-expiratory pressure (NEEP) of -4 cmH2O, (d) restoration of PEEP and (e) final control after hyper-inflation. Both RAR and bronchial C-fiber activity increased significantly compared with control when lung compliance was decreased (bronchial C-fibers: 35 +/- 5 vs. 66 +/- 13 impulses per 30 sec and RAR: 3 +/- 1 vs. 94 +/- 14 impulses per 30 sec).     

Soy Phytoestrogens Do Not Fully Reverse Changes in Rat Pituitary Castration Cells: Unbiased Stereological Study

The aim of the study was to examine the potential of the principal soy isoflavones, genistein and daidzein, or isoflavone rich soy extract to recover pituitary castration cells in orchidectomized adult male rats in comparison with the effects of estradiol. Two weeks post orchidectomy (Orx), animals received estradiol‐dipropionate, genistein, daidzein or soy extract subcutaneously for 3 weeks. Control sham‐operated (So) and Orx rats received just the vehicle. Changes in the volumes of pars distalis, of individual follicle‐stimulating hormone (FSH) and luteinizing hormone (LH) containing cells, their volume, numerical density and number were determined by unbiased design‐based stereology. The intracellular content of βFSH and βLH was estimated by relative intensity of fluorescence (RIF). Orchidectomy increased all examined stereological parameters and RIF. Compared to Orx, estradiol increased the volume of pars distalis, but reversed RIF and all morphometric parameters of gonadotropes to the level of So rats, except their number. Treatments with purified isoflavones and soy extract decreased RIF to the control So level, expressing an estradiol‐like effect. However, the histological appearance and morphometrical features of gonadotropes did not follow this pattern. Genistein increased the volume of pars distalis, decreased the volume density of LH‐labeled cells and raised the number of gonadotropes. Daidzein decreased the cell volume of gonadotropic cells but increased their number and numerical density. Soy extract induced an increase in number and numerical density of FSH‐containing cells. Therefore, it can be concluded that soy phytoestrogens do not fully reverse the Orx‐induced changes in pituitary castration cells. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.     

Perinatal and early postnatal reorganization of the subplate and related cellular compartments in the human cerebral wall as revealed by histological and MRI approaches

We analyzed the developmental history of the subplate and related cellular compartments of the prenatal and early postnatal human cerebrum by combining postmortem histological analysis with in vivo MRI. Histological analysis was performed on 21 postmortem brains (age range: 26 postconceptional weeks to 6.5 years) using Nissl staining, AChE-histochemistry, PAS–Alcian blue histochemistry, Gallyas’ silver impregnation, and immunocytochemistry for MAP2, synaptophysin, neurofilament, chondroitin sulfate, fibronectin, and myelin basic protein. The histological findings were correlated with in vivo MRI findings obtained in 30 age-matched fetuses, infants, and children. We analyzed developmental reorganization of major cellular (cell bodies, growing axons) and extracellular (extracellular matrix) components of the subplate and the developing cortex/white matter interface. We found that perinatal and postnatal reorganization of these tissue components is protracted (extending into the second year of life) and characterized by well-delineated, transient and previously undescribed structural and molecular changes at the cortex/white matter interface. The findings of this study are clinically relevant because they may inform and guide a proper interpretation of highly dynamic and hitherto puzzling changes of cortical thickness and cortical/white matter interface as described in current in vivo MRI studies.     

Does therapeutic drug monitoring (TDM) of trough concentrations suffice for optimizing preemptive therapy with ganciclovir of cytomegalovirus infections in non-renal solid organ transplant recipients?

Objectives

The aim of this study is to explore the relationship between ganciclovir exposure and clinical efficacy and/or safety in non-renal solid organ transplant (SOT) recipients receiving preemptive therapy with ganciclovir/valganciclovir and undergoing therapeutic drug monitoring (TDM)-guided dosing optimization.

Methods

Non-renal SOT recipients admitted to IRCCS Azienda Ospedaliero-Universitaria of Bologna receiving preemptive therapy with ganciclovir or valganciclovir for active cytomegalovirus (CMV) infection and who underwent at least one TDM were included. Desired ganciclovir C_min range was set at 1–3 mg/L, and average ganciclovir trough concentrations (C_min) were calculated for each patient. Reduced CMV viral load below the lower limit of quantification (LLQ) at 30 days and occurrence of myelotoxicity were selected as the primary outcome. Univariate analysis was performed by comparing patients with average C_min below or above 1 or 3 mg/L. Receiver operating characteristic (ROC) curve analysis was performed to identify the average ganciclovir C_min cut-off predictive for clinical efficacy or toxicity.

Results

Twenty-nine out of 89 retrieved patients met the inclusion criteria, with a median (interquartile [IQR]) baseline CMV viral load of 27,163 copies/mL (IQR 13 159.75–151 340.25 copies/mL). Reduced CMV viral load below the LLQ at 30 days was found in 17 patients (58.6%). No difference was found in the primary outcome between patients showing average C_min below or above 1 mg/L (100.0% vs. 53.8%; p = .25) and/or 3 mg/L (65.2% vs. 33.3%; p = .20). ROC analysis did not allow to identify an average C_min cut-off predictive of clinical efficacy or toxicity.

Conclusions

No clear relationship between ganciclovir C_min and neither CMV eradication nor safety issues was identified.