The influence of protein malnutrition on the production of GM-CSF and M-CSF by macrophages

ABSTRACT It is well established that protein malnutrition (PM) impairs immune defenses and increases susceptibility to infection. Macrophages are cells that play a central role in innate immunity, constituting one of the first barriers against infections. Macrophages produce several soluble factors, including cytokines and growth factors, important to the immune response. Among those growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). GM-CSF and M-CSF are important to monocyte and macrophage development and stimulation of the immune response process. Knowing the importance of GM-CSF and M-CSF, we sought to investigate the influence of PM on macrophage production of these growth factors. Two-month-old male BALB/c mice were subjected to PM with a low-protein diet (2%) and compared to a control diet (12%) mouse group. Nutritional status, hemogram and the number of peritoneal cells were evaluated. Additionally, peritoneal macrophages were cultured and the production of GM-CSF and M-CSF and mRNA expression were evaluated. To determine if PM altered macrophage production of GM-CSF and M-CSF, they were stimulated with TNF-α. The PM animals had anemia, leukopenia and a reduced number of peritoneal cells. The production of M-CSF was not different between groups; however, cells from PM animals, stimulated with or without TNF-α, presented reduced capability to produce GM-CSF. These data imply that PM interferes with the production of GM-CSF, and consequently would affect the production and maturation of hematopoietic cells and the immune response

What is it like to be the wife of an addicted man in Iran? A qualitative study

Drug misuse is increasing and diversifying in Iran. This study is the first to explore in detail the impact on, and ways of coping used by, spouses of addicted men in Iran. Semi-structured interviews were conducted with 24 spouses. Four main themes were identified in the data: heart-breaking news of the husband's addiction; coping alone; progressive deterioration and suffering; and disruption of family relationships and finances. Reactions upon learning of the husband's addiction involved shock and collapse, and/or fear, disbelief and confusion. Spouses tried to hide the problem and to solve the problem alone, feeling for a long time as if they were "walking in the dark" without any social support and exposed to stigma. As time had gone on they had experienced distress and turmoil, and mixed feelings towards, and loss of trust and confidence in, their husbands, whose behaviour was increasingly unreliable. This had led to impairment in the relationship, and financial stress, and a general degradation and disruption of normal family life, leading to strain for spouses, akin to a state of burnout. Present findings confirm the conclusions of similar research conducted in other countries, that substance misuse in the family can have devastating effects for spouses, on children and all aspects of family life. The situation for Iranian wives may be compounded by the relatively closed nature of family life, and the existence of culturally based attitudes, including shame, towards "family defects" such as addiction. More information and support is needed for Iranian families of addicted individuals. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted

Evaluation of matrix metalloproteinase-9 plasma levels in untreated new Relapsing-remitting multiple sclerosis patients and their first-degree family

Matrix metalloproteinase, especially Matrix metalloproteinase-9 (MMP-9) has vital roles in the disruption of blood barrier, neuroinflammation and pathogenesis of multiple sclerosis (MS) patients. The goal of this study is to estimate the plasma levels of MMP-9 in the first-degree family of MS patients. 35 untreated patients with definite RRMS (Relapsing-Remitting Multiple sclerosis) according to the McDonald criteria, 24 healthy controls (HC) and 26 high-risk families of untreated RRMS patients were enrolled in the study. Plasma levels of MMP-9 were analyzed by ELISA (enzyme-linked immunosorbent assay). Although the plasma protein levels of MMP-9 were elevated significantly in the untreated RRMS group (P < 0.05, P = 0.0203) as compared to the control group, but the family of MS patients was not significance (P = 0.208). The mean plasma MMP-9 concentration for HC, untreated RRMS and high-risk group was 322.268 pg/ml, 611.926 pg/ml and 518.939 pg/ml respectively. MMP-9 was used to understand the role of this biomarker in the pathogenesis of MS in the high-risk group. It found that plasma levels of MMP-9 in the new cases of MS were increased considerably. Confirming the importance of MMP-9 as a predictive marker in the high-risk group will be needed more researches

Evaluation of S100A12 and Apo-A1 plasma level potency in untreated new relapsing–remitting multiple sclerosis patients and their family members

Multiple sclerosis is an inflammatory disease of the spinal cord and brain. Receptor for advanced glycation end products and Apolipoprotein A1 (Apo-AI) have been recommended to have a pathogenic role in the neuroinflammatory disorder as multiple sclerosis. The purpose of this research was to measure the plasma levels of S100A12 and Apo-A1 in the first-degree family of relapsing–remitting multiple sclerosis (RRMS) patients. Plasma levels of S100A12 & Apo-A1 were evaluated via enzyme-linked immunosorbent assay in the thirty-five new cases of untreated patients with deterministic RRMS according to the McDonald criteria, twenty-four healthy controls, and twenty-six first-degree members of untreated RRMS patients (called them as high-risk group). The main findings of this study were as follows: the plasma level of S100A12 was significantly lower in the new cases of untreated RRMS (P ≤ 0.05; 0.045) and high-risk (P ≤ 0.05; 0.001) groups. Although the plasma protein level of Apo-A1 was reduced significantly in the high-risk group (P < 0.05, P = 0.003) as compared to the healthy control group, there was no significant difference in the untreated RRMS patients (P = 0.379). The plasma level of vitamin D3 in both RRMS patients and high-risk groups displayed significance reduction, although, there was no significant association between vitamin D and S100A12 & Apo-A1 levels. Given the role of S100A12 and Apo-A1 in the inflammatory process performed in the first-degree family members of the RRMS patients, which revealed a significant decrease in this group, we concluded that they can be considered as one of the contributing factors in the pathogenesis of MS, though more research is needed before assuming them as predictive biomarkers. © 2022, The Author(s)

SCSA results correlated with rate of motility reduction after ejaculation in Asthenozoospermia

Maintaining sperm motility after ejaculation is important for fertilisation. Apoptosis may play an important role to reduce sperm motility after ejaculation. The aim of this study was to perceive whether or not an increase in apoptosis reduces sperm motility in a higher degree after ejaculation and whether it can be predicted by laboratory tests, such as sperm chromatin structure assay (SCSA). Fifty-one Asthenozoospermia and 20 fertile subjects participated in this study. SCSA was applied using flow cytometry. Fluorescein-labelled inhibitors of Caspases (FLICA) method was used for assessment of active Caspase-3. Motility was assessed every 2 hr after ejaculation for 12 hr. Both SCSA and spermatozoa with active Caspase-3 were significantly correlated with the rate of motility reduction after ejaculation. In the subgroups who had SCSA = 27 and active Caspase-3 >= 40, a significant decrease in motility was observed between 2 and 4 hr after ejaculation. The result demonstrated a significant trend in the rate of sperm motility reduction with SCSA increase, which suggests SCSA may indirectly show a good scheme of apoptosis status and may forecast the rate of motility reduction after ejaculation in Asthenozoospermia

Anticonvulsant action of hippocampal dopamine and serotonin is independently mediated by D2 and 5-HT1A receptors

The present microdialysis study evaluated the anticonvulsant activity of extracellular hippocampal dopamine (DA) and serotonin (5-HT) with concomitant assessment of the possible mutual interactions between these monoamines. The anticonvulsant effects of intrahippocampally applied DA and 5-HT concentrations were evaluated against pilocarpine-induced seizures in conscious rats. DA or 5-HT perfusions protected the rats from limbic seizures as long as extracellular DA or 5-HT concentrations ranged, respectively, between 70-400% and 80-350% increases compared with the baseline levels. Co-perfusion with the selective D-2 blocker remoxipride or the selective 5-HT1A blocker WAY-100635 clearly abolished all anticonvulsant effects. These anticonvulsant effects were mediated independently since no mutual 5-HT and DA interactions were observed as long as extracellular DA and 5-HT levels remained within these protective ranges. Simultaneous D-2 and 5-HT1A receptor blockade significantly aggravated pilocarpine-induced seizures. High extracellular DA (> 1000% increases) or 5-HT (> 900% increases) concentrations also worsened seizure outcome. The latter proconvulsive effects were associated with significant increases in extracellular glutamate (Glu) and mutual increases in extracellular monoamines. Our results suggest that, within a certain concentration range, DA and 5-HT contribute independently to the prevention of hippocampal epileptogenesis via, respectively, D-2 and 5-HT1A receptor activation