Sex hormone-binding globulin (SHBG) is a plasma protein synthesized and secreted by the liver. Its initial description stemmed from its ability to bind estrogens and androgens and its capacity to regulate the free concentration of the steroids that bind to it. Additionally, it participates in signal transduction for certain steroid hormones at the cell membrane. It binds with high affinity to a specific membrane receptor (RSHBG) in prostate stromal and epithelial cells, wherein the SHBG·RSHBG complex forms. An appropriate steroid binds to this complex and results in increases of intracellular cAMP. These two disparate functions of SHBG, regulation of the concentration of free steroids in plasma and signal transduction in selected tissues, raise the question of how its synthesis and secretion might be regulated so as to best perform these two disparate functions. In this paper we demonstrate that SHBG is produced in human prostate cancer cell lines (LNCaP, DU 145, and PC 3) as well as in cultured human prostate epithelial and stromal cells. In addition, in tissue sections of human prostate, we demonstrate the presence of SHBG (immunocytochemistry) and SHBG mRNA (in situhybridization). These observations are consistent with the hypothesis that SHBG, destined to participate in signaling at the cell membrane, is locally regulated and produced.
Systemic inflammation has emerged as a promising marker and potential mechanism underlying post-traumatic stress disorder (PTSD). The relationship between posttraumatic stress pathology and systemic inflammation has not, however, been consistently replicated and is potentially confounded by comorbid illness or injury, common complications of trauma exposure. We analyzed a large naturalistic cohort sharing a discrete physical and mental health trauma from the destruction of the World Trade Center (WTC) towers on September 11, 2001 (n = 641). We evaluated the relationship between multiple physical and mental health related indices collected through routine evaluations at the WTC Environmental Health Center (WTC EHC), a treatment program for community members exposed to the disaster. C-Reactive Protein (CRP), a marker of systemic inflammation, was examined in relation to scores for PTSD, PTSD symptom clusters (re-experiencing, avoidance, negative cognitions/mood, arousal), depression and anxiety, while controlling for WTC exposures, lower respiratory symptoms, age, sex, BMI and smoking as potential risks or confounders. CRP was positively associated with PTSD severity (p < 0.001), trending toward association with depression (p = 0.06), but not with anxiety (p = 0.27). CRP was positively associated with re-experiencing (p < 0.001) and avoidance (p < 0.05) symptom clusters, and trended toward associations with negative cognitions/mood (p = 0.06) and arousal (p = 0.08). In this large study of the relationship between CRP and posttraumatic stress pathology, we demonstrated an association between systemic inflammation and stress pathology (PTSD; trending with depression), which remained after adjusting for potentially confounding variables. These results contribute to research findings suggesting a salient relationship between inflammation and posttraumatic stress pathology.
The assault and subsequent collapse of the World Trade Center towers in New York City on September 11, 2001 (9/11), released more than a million tons of debris and dust into the surrounding area, engulfing rescue workers as they rushed to aid those who worked in the towers, and the thousands of nearby civilians and children who were forced to flee. In December 2015, almost 15 years after the attack, and 5 years after first enactment, Congress reauthorized the James Zadroga 9/11 Health and Compensation Act, a law designed to respond to the adverse health effects of the disaster. This reauthorization affords an opportunity to review human inhalation exposure science in relation to the World Trade Center collapse. In this Special Article, we compile observations regarding the collective medical response to the environmental health disaster with a focus on efforts to address the adverse health effects experienced by nearby community members including local residents and workers. We also analyze approaches to understanding the potential for health risk, characterization of hazardous materials, identification of populations at risk, and shortfalls in the medical response on behalf of the local community. Our overarching goal is to communicate lessons learned from the World Trade Center experience that may be applicable to communities affected by future environmental health disasters. The World Trade Center story demonstrates that communities lacking advocacy and preexisting health infrastructures are uniquely vulnerable to health disasters. Medical and public health personnel need to compensate for these vulnerabilities to mitigate long-term illness and suffering.
There is a paucity of research that illustrates the interplay between HIV/AIDS treatment and prevention programs. We describe the central role that public access to antiretroviral (ARV) medication has played in the development and efficacy of HIV/AIDS prevention programming in Khayelitsha, a resource-poor township in the Western Cape of South Africa. We document the range of preventive interventions and services available in Khayelitsha since the early 1990s and explore the impact of ARV availability on prevention efforts and disease stigma on the basis of extensive indepth interviews, supplemented by data collection. The information gathered suggests that the introduction of the mother-to-child-transmission (MTCT) prevention programs in 1999 and the three HIV treatment clinics run by Doctors Without Borders/ Médecins Sans Frontières (MSF) in 2000 were turning points in the region’s response to the HIV/AIDS epidemic. These programs have provided incentives for HIV testing, galvanized HIV/AIDS educators to reach populations most at risk, and decreased the HIV incidence rates in Khayeltisha compared to other areas in the Western Cape. Lessons learned in Khayelitsha about the value of treatment availability in facilitating prevention efforts can inform the development of comprehensive approaches to HIV/ AIDS in other resource-poor areas.
1 June 2015 in Journal of Occupational and Environmental Medicine
Destruction of the World Trade Center (WTC) towers on September 11, 2001, released massive dust, gas, and fumes with environmental exposures for community members. Many community members have lower respiratory symptoms (LRSs) that began after September 11, 2001, and remain persistent. We evaluated whether systemic inflammation measured by C-reactive protein was associated with WTC dust exposures, persistent LRS, and lung function. Community members self-referred for the treatment of symptoms related to September 11, 2001. C-reactive protein and lung function measurements, including spirometry and forced oscillation tests (impulse oscillometry system), were included as routine analyses in patients (2007 to 2012). Increased C-reactive protein levels were associated with the type of WTC dust exposure, LRS, reduced spirometry, and increased forced oscillation measurements (n = 724). Ongoing systemic inflammation measured years after the event was associated with WTC dust exposures, persistent LRS, and abnormal lung function in a community cohort. These findings have implications for treatment and surveillance.