Phagocytosis and cellular metabolism

Summary The uptake of foreign particles by mouse and human macrophages influenced by various metabolic inhibitors was examined in order to obtain further informations about the energy-dependent mechanisms which are involved in the phagocytic process. The inhibitors employed were iodoacetate, fluoroacetate, fluoride, malonate, sodium azide, 2-4-dinitrophenol, cycloheximide and ouabain. These substances were rested on monolayer cultures and the phagocytosis assay was performed by using zymosan suspension in the nutrient media. The quantitation of phagocytosis was obtained by the direct count of intracellular zymosan particles (immersion microscopy, 100x) and the results were evaluated and compared by biometrical analysis. The effects of these inhibitors on phagocytosis and their relation with the metabolic intracellular pathways are discussed.     

Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin‐10 in cervical neoplastic lesions

A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high‐risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (IL‐10). This production of IL‐10, in conjunction with HPV infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the IL‐10‐producing cellular phenotype, and investigate the influence of host and HPV factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in IL‐10 production by keratinocytes, macrophages and Langerhans cells in high‐grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30 years, and was also correlated with high viral load, and infection with a single HPV type, particularly high‐risk HPVs. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different IL‐10‐producing cellular phenotypes in cervical cancer samples, and samples classified as high‐grade cervical lesions (cervical intraepithelial neoplasia stages II and III). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression.     

Obstructive sleep apnea syndrome: effect of respiratory events and arousal on pulse wave amplitude measured by photoplethysmography in NREM sleep

The objective of the study is to evaluate changes in finger pulse wave amplitude (PWA), as measured by photoplethysmography, and heart rate (HR), related to obstructive respiratory events and associated arousals during sleep. We analyzed 1,431 respiratory events in NREM sleep from 12 patients according to (1) the type of event (apnea, hypopnea, upper airway resistance episode) and (2) the duration of the associated EEG arousal (>10, 3–10, <3 s). Obstructive respiratory events provoked a relative bradycardia and vasodilation followed by HR increase and vasoconstriction. Relative PWA changes were significantly greater than HR changes. These responses differed significantly according to EEG-arousal grades (time×arousal interaction, p<0.0001), with longer arousals producing greater responses, but not to the type of respiratory event (time×event interaction, p = ns). Obstructive respiratory events provoke HR and PWA changes, the magnitude seemingly related to the intensity of central nervous activation, with PWA changes greater than HR. PWA obtained from a simple pulse oxymeter might be a valuable method to evaluate sleep fragmentation in sleep breathing disorders.     

Impact of comorbidity on outcome in kidney transplant recipients: a retrospective study in Italy

The aim of this study was to relate in-hospital mortality (IHM), cardiovascular events (CVEs) and non-immunologic comorbidity evaluated on the basis of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codification, in Italian kidney transplant recipients (KTRs). We evaluated IHM and admissions due to CVEs between 2000 and 2013 recorded in the database of the region Emilia Romagna. The Elixhauser score was calculated for evaluation of non-immunologic comorbidity. Three main outcomes (i.e. IHM, admission due to major CVEs and combined outcome) were the dependent variables of the multivariate models, while age, gender and Elixhauser score were the independent ones. During the examined period, a total of 9063 admissions in 3648 KTRs were recorded; 1945 patients were males (53.3 %) and 1703 females (46.7 %) and the mean age was 52.9 ± 13.1 years. The non-immunological impaired status of the KTRs, examined by the Elixhauser score, was 3.88 ± 4.29. During the 14-year follow-up period, IHM for any cause was 3.2 % (n = 117), and admissions due to CVEs were 527 (5.8 %). Age and comorbidity were independently associated with CVEs, IHM and the combined outcome. Male gender was independently associated with IHM and combined outcome, but not with CVEs. Evaluation of non-immunological comorbidity is important in KTRs and identification of high-risk patients for major clinical events could improve outcome. Moreover, comorbidity could be even more important in chronic kidney disease patients who are waiting for a kidney transplant.     

Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies

Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.     

Neuroendocrine response to clomipramine and desipramine--the evidence of partial determination by heredity and sex

A single dose of clomipramine, 10 mg i.v., or desipramine, 25 mg i.m., was administered to seven healthy young sibling pairs in a randomized cross-over experiment. The response of serum growth hormone, prolactin and cortisol was measured. The main findings were (1) sex differences in the growth hormone and cortisol response to desipramine and (2) a significant genetic component of the prolactin and cortisol response to desipramine as indicated by significantly (p less than 0.05) lower within-pair than between-pair variance in the sibling pairs but not random pairs of the experimental subjects.