Inhibition of p38 mitogen activated protein kinase increases lipopolysaccharide induced inhibition of apoptosis in neutrophils by activating extracellular signal-regulated kinase

BACKGROUND: Prolonged polymorphonuclear neutrophil (PMN) survival has been implicated in tissue injury after sepsis. Previously we reported that lipopolysaccharide (LPS) inhibits PMN apoptosis via the activation of the extracellular signal-regulated kinase (ERK). Conversely, the p38 mitogen activated protein kinase (MAPK) pathway is involved in the spontaneous apoptosis of PMNs. The interaction between these 2 pathways and their ability to regulate apoptosis during sepsis remain largely undefined. We hypothesize that there is interaction between the ERK and p38 pathways during sepsis. METHODS: PMNs were isolated from healthy volunteers by Ficoll gradient centrifugation and red blood cell sedimentation. Cells were then pretreated for 1 hour with the ERK inhibitor (PD98059, 10 micromol/L), p38 inhibitor (SB203580, 1 micromol/L), or vehicle. After treatment with LPS, apoptosis and MAPK activity were correlated. RESULTS: LPS stimulation significantly inhibits PMN apoptosis compared with unstimulated cells. Furthermore, inhibition of ERK significantly abrogates this effect, whereas inhibition of p38 augments LPS induced inhibition of apoptosis. Elk-1 phosphorylation (ERK target) is significantly increased by LPS alone and by inhibition of the p38 pathway during LPS stimulation. This correlates with ERK phosphorylation by Western blot. CONCLUSIONS: These data show that p38 inhibition enhances ERK activity during endotoxemia. Furthermore, these data suggest that cooperation between ERK and p38 MAPK pathways dictates the apoptotic potential of PMNs during inflammatory states.     

Influence of an optimized non-ionic emulsifier blend on properties of oil-in-water emulsions.

Properties of oil-in-water emulsions containing non-ionic emulsifiers were evaluated in relation to nature of the dispersed phase, emulsifier composition and processing parameters. Particle size of mineral oil (hydrocarbons)-in-water emulsions was independent of the HLB of an optimized emulsifier blend, whereas, the particle size of olive oil (triglycerides)-in-water emulsions was the smallest at the optimum HLB of the emulsifier blend. The non-ionic emulsifiers reduced the particle size of mineral oil emulsions more efficiently than that of olive oil emulsions. Contrary to previously published reports, the nature of the dispersed phase, HLB of the emulsifier blend or the initial particle size of emulsions showed no influence on the final particle stability of the emulsions. This difference was attributed to the optimization of the emulsifier blend and processing parameters in the preparation of emulsions.     

A comparison of tubal ring and Madlener's techniques of tubal ligation in postpartum cases

Compares Madlener's traditional technique and a new method of tubal ligation as sterilization procedures on postpartum women. The new tubal ring ligation procedure has been welcomed because of its nonreliance on electrocautery, a procedure which has proved to be unsafe. This study is based on the sterilization and follow-up of 300 postpartum women aged 21 to 40. Follow-up was carried out at day 7, at 6 months and at 1 year (78% of sample). Except for a minor surgical complication in 1 subject of each group, surgery was uneventful, averaging 7.9 and 9.0 minutes for tubal ligation and Madlener's technique, respectively. Postoperative complication, common to this type of surgery and unrelated to comparative aspects of the 2 surgeries were noted. Follow-up showed the commonest complaints to be backache, leukorrhea and general weakness. These symptoms, however, are very common in hospital patients. The incidence of backache, though, was significantly higher in the group of women sterilized by the tubal ring technique as compared with Madlener's. Neither group was significantly different in the incidence of postoperative menstrual irregularities; after 1 year the most common abnormality was excessive or scanty menstrual cycle. Pelvic findings showed a slight increase in the number of cervical erosions and endocervicitis in the tubal ring group as opposed to Madlener's; these findings, though, are only coincidental and have no bearing on the method of sterilization. The study also demonstrates that either method can safely be performed in postpartum women.     

Effect of prolactin on tetracycline binding to human spermatozoa.

The effect of different concentrations of prolactin (0 to 60 ng) on the release of tetracycline from human spermatozoa labeled with 7-3H-tetracycline hydrochloride was studied. Prolactin significantly enhanced the release of bound tetracycline, indicating that prolactin may influence the processes associated with sperm capacitation.     

Selective Internal Radiation Therapy with Yttrium-90 for Intrahepatic Cholangiocarcinoma: A Systematic Review on Post-Treatment Dosimetry and Concomitant Chemotherapy

Selective internal radiation therapy (SIRT) with yttrium-90 (⁹⁰Y)-loaded microspheres is increasingly used for the treatment of Intrahepatic Cholangiocarcinoma (ICC). Dosimetry verifications post-treatment are required for a valid assessment of any dose-response relationship. We performed a systematic review of the literature to determine how often clinics conducted post-treatment dosimetry verification to measure the actual radiation doses delivered to the tumor and to the normal liver in patients who underwent SIRT for ICC, and also to explore the corresponding dose-response relationship. We also investigated other factors that potentially affect treatment outcomes, including the type of microspheres used and concomitant chemotherapy. Out of the final 47 studies that entered our study, only four papers included post-treatment dosimetry studies after SIRT to quantitatively assess the radiation doses delivered. No study showed that one microsphere type provided a benefit over another, one study demonstrated better imaging-based response rates associated with the use of glass-based TheraSpheres, and two studies found similar toxicity profiles for different types of microspheres. Gemcitabine and cisplatin were the most common chemotherapeutic drugs for concomitant administration with SIRT. Future studies of SIRT for ICC should include dosimetry to optimize treatment planning and post-treatment radiation dosage measurements in order to reliably predict patient responses and liver toxicity.     

Water treatment and handwashing behaviors among non-pregnant friends and relatives of participants in an antenatal hygiene promotion program in Malawi

Access to safe drinking water and improved hygiene are essential for preventing diarrheal diseases. To integrate hygiene improvement with antenatal care, free hygiene kits (water storage containers, water treatment solution, soap) and educational messages were distributed to pregnant women at antenatal clinics in Malawi. We assessed water treatment and hygiene practices of 275 non-pregnant friends and relatives of the hygiene kit recipients at baseline and follow-up nine months later to measure program impact on non-participants in the same communities. At follow-up, friends and relatives who did not receive kits or education were more likely than at baseline to purchase and use water treatment solution (25% versus 1%; P < 0.0001) and demonstrate correct handwashing practices (60% versus 18%; P < 0.0001). This antenatal clinic-based program resulted in improved water treatment and hygiene behaviors among non-pregnant friends and relatives living in the same communities as hygiene kit recipients, suggesting that program benefits extended beyond direct beneficiaries.     

Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation

BACKGROUND: Chronic coinfection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) has been associated with an increased HIV viral load and more rapid disease progression, perhaps related to HSV-2-associated alterations in host immunity. METHODS: Studies were nested within (1) a cross-sectional study of men coinfected with HIV and HSV-2 and (2) women not infected with HIV, both before and after HSV-2 acquisition. HSV-2 infection status was determined by ELISA. HIV-specific CD8(+) T cell epitopes were mapped, and proliferation of HIV-specific cells was also assessed. Systemic inflammatory and regulatory T cell populations were assayed by flow cytometry. RESULTS: The breadth of both the HIV-specific CD8(+) T cell interferon-gamma and proliferative responses was reduced in participants coinfected with HIV and HSV-2, independent of the HIV plasma viral load and CD4(+) T cell count, and the magnitude of the responses was also reduced. HSV-2 infection in this group was associated with increased T cell CD38 expression but not with differences in the proportion of CD4(+) FoxP3(+) regulatory T cells. However, in women not infected with HIV, acquisition of HSV-2 was associated with an increase in the proportion of regulatory T cells. CONCLUSIONS: HSV-2 coinfection was associated with reduced HIV-specific T cell responses and systemic inflammation. The immune effects of HSV-2 may underlie the negative impact that this coinfection has on the clinical course of HIV infection.