Comparison between VDR analogs and current immunosuppressive drugs in relation to CXCL10 secretion by human renal tubular cells

During kidney allograft rejection, CXC chemokine ligand 10 (CXCL10)–CXC chemokine receptor 3 (CXCR3) trafficking between peripheral blood and tissues initiates alloresponse and perpetuates a self‐inflammatory loop; thus, CXCL10–CXCR3 axis could represent a pharmacologic target. In this perspective, immunosuppressors targeting graft‐resident cells, beside immune cells, could be very advantageous. Vitamin D receptor (VDR) agonists exhibit considerable immunomodulatory properties. This study aimed to investigate whether elocalcitol and BXL‐01‐0029 could decrease the expression of CXCL10 in activated renal tubular cells in vitro and thus be useful in kidney allograft rejection treatment. Experiments were performed in human tubular renal cells stimulated with interferon‐γ + tumor necrosis factor‐α with and without VDR agonists, tacrolimus, sirolimus, hydrocortisone, methylprednisolone, cyclosporin A and mycophenolate mofetil. CXCL10 protein secretion and gene expression were measured by ELISA and by quantitative PCR. Specific inhibitors were used to investigate intracellular pathways involved in tubular cells activation. For IC₅₀ determination and comparison, dose‐response curves with VDR agonists, tacrolimus and mycophenolic acid were performed. Elocalcitol and BXL‐01‐0029 inhibited CXCL10 secretion by renal cells, without affecting cell viability, while almost all the immunosuppressors were found to be ineffective, except for tacrolimus and mycophenolate mofetil. BXL‐01‐0029 was the most potent drug and, notably, it was found to be capable of allowing reduction in tacrolimus‐inhibitory doses. Our data suggest that BXL‐01‐0029 could potentially be a dose‐reducing agent for conventional immunosuppressors in kidney rejection management.     

Importance of semen preparation in avoidance of reduced in vitro fertilization results attributable to bacteria

Although the physical treatment of semen for IVF and related procedures is sufficient to remove most organisms present in semen, the pathogenic varieties tend to be more resistant. The supplementation of oocyte culture medium with both penicillin and streptomycin was associated with the eradication of 100% of organisms in the current study. In these circumstances, the presence of pathogenic organisms in the untreated semen is not associated with reduced oocyte fertilization in vitro.     

Human embryo viability related to freezing and thawing procedures

Freezing and thawing procedures did not affect the chances of successful transfer of human embryos. The postimplantation viability of frozen-thawed embryos was equivalent to that of fresh, immediately transferred embryos. Selection of the embryos that were more suitable for freezing did influence the pregnancy rate after transfer of the remaining fresh embryos. The therapeutic efficacy of in vitro fertilization and embryo transfer programs will be greatly increased if only one embryo is transferred in the in vitro fertilization cycle, the others being separately frozen for further embryo transfer in subsequent cycles.     

Neurosteroid secretion in panic disorder

Evidence that neurosteroids have anxiolytic effects in animal models of anxiety has suggested that alterations of neurosteroid secretion might be implicated in the pathogenetic mechanisms of anxiety disorders in humans. In 25 female patients with panic disorder (PD) and 11 healthy female controls, we measured plasma concentrations of progesterone (PROG), pregnenolone (PREG), allopregnanolone (3alpha,5alpha-tetrahydroprogesterone=3alpha,5alpha-THPROG), dehydroepiandrosterone (DHEA) and tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) during a drug-free month and during the following month of paroxetine therapy. The neurosteroids were measured during the early follicular phase, the mid-luteal phase and the premenstrual phase of both months (days 7, 22 and 27 from the beginning of the cycle). Significantly higher levels in patients than controls were found in PROG during the mid-luteal phase of both months, PREG in the premenstrual phase in the drug-free month, 3alpha,5alpha-THPROG during the follicular phase of the drug-free month and during the premenstrual phase of the therapy month, and 3alpha,5alpha-THDOC during the premenstrual phases of both months. DHEA levels did not differ in patients and controls. These results suggest that neurosteroids in PD are hypersecreted, possibly as an attempt to counteract the anxiogenic underlying hyperactivity of the hypothalamo-pituitary-adrenal axis and to improve a reduced GABA(A) receptor sensitivity.     

Dopamine release in human ventral striatum and expectation of reward

Using the ability of [11C]raclopride to compete with dopamine for D(2)/D(3) receptors, we investigated by positron emission tomography the effect of placebo (saline) injection on dopamine release in the ventral striatum of patients with Parkinson's disease. We found evidence for placebo-induced dopamine release of similar magnitude to that reported in healthy volunteers after amphetamine administration. However, in contrast to the dorsal striatum, there were no differences in [11C]raclopride binding potential changes between patients who experienced the reward (those who reported placebo-induced clinical benefit) and those who did not. We conclude that the release of dopamine in the ventral striatum (nucleus accumbens) is related to the expectation of reward and not to the reward itself. These observations have potential implications for the treatment of drug addiction.     

Dose and volume as predictive factors of pulmonary toxicity

Dose and volume and their correlation with the development of pulmonary toxicity are among the most widely studied and validated factors in radiotherapy. Most common treatment planning systems allow prompt assessment of Vdose and Mean Lung Dose (MLD). The former represents the percentage of normal lung parenchyma receiving a dose equal to or higher than the established threshold dose; the latter corresponds to the mean dose delivered to the normal lung parenchyma. Most important studies reported on the subject and threhold values recommended for Vdose and MLD are analyzed. The monitoring system of late toxicity used by the authors is presented.     

A census-based socio-economic status (SES) index as a tool to examine the relationship between mental health services use and deprivation

This paper discusses the development and application of a socio-economic status (SES) index, created to explore the relationship between socio-economic variables and psychiatric service use. The study was conducted in a community-based mental health service (CMHS) in Verona, Northern Italy, utilising service use data from 1996. An ecological SES index was constructed through a factor analysis from 1991 Census data, at census block level. Three factors reflected the following domains: the educational-employment sector (with four components), the relational network (with three components) and the material conditions (with three components). All service users were assigned a SES value, according to their place of residence in 1996. When these data were explored spatially, using ArcView 8.3, an association was observed between socio-economic deprivation and psychiatric service use. The SES index was then successfully validated using occupational status at the individual level. This study confirms the usefulness of developing and validating an ecological census-based SES index, for service planning and resource allocation in an area with a community-based system of mental health care.