Domestic violence and child nutrition in Liberia.

Domestic violence against women is endemic globally and is an important social problem in its own right. A compounding concern is the impact of domestic violence against mothers on the nutritional status of their children. Liberia is an apt setting to examine this understudied topic, given the poor nutritional status of young children, high rate of domestic violence against women, and prolonged period of conflict that included systematic sexual violence against women. We expected that maternal exposure to domestic violence would predict lower anthropometric z-scores and higher odds of stunting, wasting, and underweight in children less than five years. Using data from 2467 mother-child dyads in the 2007 Liberia Demographic and Health Survey (LDHS) undertaken between December 24, 2006 and April 19, 2007, we conducted descriptive and multivariate analyses to examine the total, unadjusted and adjusted associations of maternal exposure to domestic violence with these anthropometric measures in children. Maternal reports of sexual domestic violence in the prior year predicted lower adjusted z-scores for height-for-age and weight-for-height as well as higher odds of stunting and underweight. The findings underscore the needs to (1) enhance and enforce conventional and customary laws to prevent the occurrence of domestic violence; (2) treat maternal survivors of domestic violence and screen their children for nutritional deficits; (3) heighten awareness of the intergenerational implications especially of recent sexual domestic violence; and (4) clarify the biological and behavior pathways by which domestic violence may influence child growth, thereby mitigating early growth failure and its adverse implications into adulthood.

Prostate secretions from men with chronic pelvic pain syndrome inhibit proinflammatory mediators.

PURPOSE: In the past numerous chemokines have been noted in the expressed prostatic secretions of patients with chronic prostatitis/chronic pelvic pain syndrome. We examined the functional effects of chemokines in expressed prostatic secretions of patients with chronic pelvic pain syndrome. MATERIALS AND METHODS: We studied the functional effects of expressed prostatic secretions on human monocytes by examining monocyte chemotaxis in response to monocyte chemoattractant protein-1, a major chemoattractant previously identified in chronic prostatitis/chronic pelvic pain syndrome cases. We determined effects on cellular signaling by quantifying intracellular calcium increase in monocytes and nuclear factor-κB activation in normal prostate epithelial cells. RESULTS: Results show that the monocyte chemoattractant protein-1 in expressed prostatic secretions is nonfunctional with an inability to mediate human monocyte chemotaxis, or mediate signaling in monocytes or prostate epithelial cells. This lack of functionality could be extended to other proinflammatory cytokines, such as interleukin-1ß and tumor necrosis factor-α, when incubated with expressed prostatic secretions from patients with chronic pelvic pain syndrome. The mechanism underlying this apparent ability to modulate proinflammatory cytokines involves heat labile extracellular proteases that mediate the inhibition of immune and prostate epithelial cell function. CONCLUSIONS: These results may have implications for the design of specific diagnostic and therapeutic methods targeted toward the complete resolution of prostate inflammatory insults.

Activation-induced degradation of FLIP(L) is mediated via the phosphatidylinositol 3-kinase/Akt signaling pathway in macrophages.

Cellular FLIP (Flice-like inhibitory protein) is critical for the protection against death receptor-mediated cell apoptosis. In macrophages, FLIP long (FLIP(L)) and FLIP short (FLIP(S)) mRNA was induced by tumor necrosis factor (TNF) alpha, mediated through NF-kappaB. However, we observed TNFalpha reduced the protein level of FLIP(L), but not FLIP(S), at 1 and 2 h. Similar results were observed with lipopolysaccharide. The reduction of FLIP(L) by TNFalpha was not mediated by caspase 8, or through JNK or Itch, but was suppressed by inhibition of the phosphatidylinositol 3-kinase/Akt pathway employing chemical inhibitors, a dominant negative Akt-1, or Akt-1 small interfering RNA. The reduction of FLIP(L) resulted in the short term induction of caspase 8-like activity, which augmented NF-kappaB activation. A co-immunoprecipitation assay demonstrated that Akt-1 physically interacts with FLIP(L). Moreover, TNFalpha enhanced FLIP(L) serine phosphorylation, which was increased by activated Akt-1. Serine 273, a putative Akt-1 phosphorylation site in FLIP(L), was critical for the activation-induced reduction of FLIP(L). Thus, these observations document a novel mechanism where by TNFalpha facilitates the reduction of FLIP(L) protein, which is dependent on the phosphatidylinositol 3-kinase/Akt signaling.

Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 signaling.

Macrophages are important mediators of chronic inflammation and are prominent in the synovial lining and sublining of patients with rheumatoid arthritis (RA). Recently, we demonstrated increased TLR2 and TLR4 expression and increased response to microbial TLR2 and TLR4 ligands in macrophages from the joints of RA. The current study characterized the expression of the 96-kDa heat shock glycoprotein (gp96) in the joints of RA and its role as an endogenous TLR ligand to promote innate immunity in RA. gp96 was increased in RA compared with osteoarthritis and arthritis-free control synovial tissues. The expression of gp96 strongly correlated with inflammation and synovial lining thickness. gp96 was increased in synovial fluid from the joints of RA compared with disease controls. Recombinant gp96 was a potent activator of macrophages and the activation was mediated primarily through TLR2 signaling. The cellular response to gp96 was significantly stronger with RA synovial macrophages compared with peripheral blood monocytes from RA or healthy controls. The transcription of TLR2, TNF-alpha, and IL-8, but not TLR4, was significantly induced by gp96, and the induction was significantly greater in purified RA synovial macrophages. The expression of TLR2, but not TLR4, on synovial fluid macrophages strongly correlated with the level of gp96 in the synovial fluid. The present study documents the potential role of gp96 as an endogenous TLR2 ligand in RA and provides insight into the mechanism by which gp96 promotes the chronic inflammation of RA, identifying gp96 as a potential new therapeutic target.

Monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha as possible biomarkers for the chronic pelvic pain syndrome.

PURPOSE: The chronic pelvic pain syndrome is characterized by pelvic pain, voiding symptoms and varying degrees of inflammation within expressed prostatic secretions. We evaluated the chemokines monocyte chemoattractant protein 1 (CCL2) and macrophage inflammatory protein-1alpha (CCL3) in expressed prostatic secretions to identify marker increases associated with inflammatory (IIIA) and noninflammatory (IIIB) chronic pelvic pain syndrome. In addition, chemokine levels were correlated with clinical pain as determined by the National Institutes of Health chronic prostatitis symptom index. MATERIALS AND METHODS: Expressed prostatic secretions were collected by digital rectal examination, and evaluated by enzyme linked immunosorbent assays for monocyte chemoattractant protein 1 and macrophage inflammatory protein-1alpha in 154 patients including controls (13), those with benign prostatic hyperplasia (54), chronic pelvic pain syndrome IIIA (37) and IIIB (50). Monocyte chemoattractant protein 1 and macrophage inflammatory protein-1alpha levels were compared between IIIA, IIIB and the control subgroups, and correlated against the chronic prostatitis symptom index and pain subscore using a Spearman test. RESULTS: Mean levels of monocyte chemoattractant protein 1 in the control, inflammatory benign prostatic hyperplasia, noninflammatory benign prostatic hyperplasia, inflammatory chronic pelvic pain syndrome and noninflammatory chronic pelvic pain syndrome were 599.4, 886.0, 1,636.5, 3,261.2 and 2,272.7 pg/ml, respectively. Mean levels of macrophage inflammatory protein-1alpha in the control, inflammatory benign prostatic hyperplasia, noninflammatory benign prostatic hyperplasia, IIIA chronic pelvic pain syndrome and IIIB chronic pelvic pain syndrome were 140.1, 299.4, 238.7, 1,057.8 and 978.4 pg/ml, respectively. For each cytokine both chronic pelvic pain syndrome subtypes had statistically higher levels than the control group and patients with benign prostatic hyperplasia (p = 0.0002). Receiver operating curves using monocyte chemoattractant protein 1 levels greater than 704 pg/ml and macrophage inflammatory protein-1alpha greater than 146 pg/ml identified patients with chronic pelvic pain syndrome with an accuracy of 90% from control patients. Macrophage inflammatory protein-1alpha levels (p = 0.0007) correlated with the pain subscore of the chronic prostatitis symptom index while monocyte chemoattractant protein 1 (p = 0.71) did not. CONCLUSIONS: Monocyte chemoattractant protein 1 and macrophage inflammatory protein-1alpha within the prostatic fluid in both chronic pelvic pain syndrome subtypes provide candidate future biomarkers for chronic pelvic pain syndrome. In addition, macrophage inflammatory protein-1alpha increase in expressed prostatic secretions provides a new marker for clinical pain in chronic pelvic pain syndrome patients. Given these findings prostatic dysfunction likely has a role in the pathophysiology of this syndrome. These chemokines may serve as effective diagnostic markers and modulators against the chemokines could provide an attractive treatment strategy in individuals with chronic pelvic pain syndrome.