Contribution of a Streptococcus mutans antigen expressed by a Salmonella vector vaccine in dendritic cell activation

A Salmonella vector vaccine expressing the saliva-binding region (SBR) of the adhesin AgI/II of Streptococcus mutans has been shown to induce a mixed Th1/Th2 anti-SBR immune response in mice and to require Toll-like receptor 2 (TLR2), TLR4, and MyD88 signaling for the induction of mucosal anti-SBR antibody responses. Since dendritic cells (DC) are critical in innate and adaptive immunity, the present study assessed the role of SBR expression by the vector vaccine in DC activation. Bone marrow-derived DC from wild-type and TLR2, TLR4, and MyD88 knockout mice were stimulated with Salmonella vector BRD509, the SBR-expressing Salmonella vector vaccine BRD509(pSBRT7), or SBR protein, and the DC responses to different stimuli were compared by assessing costimulatory molecule expression, cytokine production, and signaling pathways. The DC response to both BRD509(pSBRT7) and BRD509 was dependent mainly on TLR4. BRD509(pSBRT7) and BRD509 induced upregulation of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) expression. Lower levels of interleukin-10 (IL-10) and IL-12p40 were produced by BRD509(pSBRT7)-stimulated DC than by BRD509-stimulated DC. Furthermore, BRD509(pSBRT7)-stimulated DC showed decreased p38 phosphorylation compared to that induced by DC stimulated with BRD509. However, BRD509(pSBRT7)-treated DC produced a higher level of IL-6 than BRD509-stimulated cells. The low IL-12p40 and high IL-6 cytokine profile expressed by BRD509(pSBRT7)-stimulated DC may represent a shift toward a Th2 response, as suggested by the increased expression in Jagged-1. These results provide novel evidence that a heterologous protein expressed by a Salmonella vector vaccine can differentially affect DC activation.     

Abortion care for adolescent and young women

Background

Unintended pregnancy among adolescents (10–19 years) and young women (20–24 years) is a global public health problem. Adolescents face challenges in accessing safe abortion care.

Objective

To determine, via a systematic data review, whether abortion care for adolescent and young women differs clinically from that for older women.

Methods

In a comprehensive data review, the Cochrane Central Register of Controlled Trials, MEDLINE, and POPLINE databases were searched from the earliest data entered until November 2012. Randomized controlled trials and observational studies comparing effectiveness, safety, acceptability, and long-term sequelae of abortion care between adolescent/young women and older women were identified. Two reviewers independently extracted data, and the Cochrane guidelines and Newcastle–Ottawa Scale were used for quality assessment.

Results

In total, there were 25 studies including 346 000 women undergoing first- and second-trimester medical abortion, vacuum aspiration, or dilation and evacuation. Effectiveness and overall complications were similar among age groups. However, younger women had an increased risk for cervical laceration and a decreased risk of uterine perforation and mortality. Satisfaction and long-term depression were similar between age groups. Except for less uptake of intrauterine devices among adolescents, age did not affect post-abortion contraception.

Conclusions

Evidence from various healthcare systems indicates that abortion is safe and efficacious among adolescent and young women. Clinical services should promote access to safe abortion for adolescents.     

Superoxide dismutase in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection

Purpose

Polycystic ovary syndrome (PCOS) is associated with oxidative stress (OS) and serum superoxide dismutase (SOD) activity has been reported with mixed results. The objective of this study was to examine the activity of SOD both in the serum and FF from women with PCOS undergoing ICSI, as well as the expression of Cu/Zn-SOD mRNA in the cells recovered from the FF.

Methods

Forty women undergoing an ICSI trial were divided into: group I, included 20 PCOS cases, group II included 20 age-matched controls with tubal factor infertility. Both groups were similarly stimulated. A total of 204 metaphase II (MII) oocytes were aspirated; (108) from PCOS, and (96) from the control group. SOD activities in the serum and FF, as well as Cu/Zn-SOD (SOD1) mRNAs in follicular fluid (FF) cells were analyzed.

Results

There was a statistically highly significant decrease (p < 0.001) both in the mean serum SOD (45.56 ± 18.06) and FF SOD activity (42.49 ± 11.46) in PCOS than the control group (77.38 ± 7.82), (74.37 ± 6.15) respectively. The mean relative levels of Cu, Zn SOD mRNAs was significantly lower (p < 0.001) in cells isolated from the FF in PCOS (0.36 ± 0.14) than the control group (0.81 ± 0.15). SOD activity in FF had no effects on fertilization rate (p > 0.05), or embryo quality after intracytoplasmic sperm injection (ICSI).

Conclusion

Although decreased SOD activity in FF has no effect on fertilization rate and/or embryo quality, serum SOD activity could be a clinical parameter for determining systemic oxidative stress in PCOS.     

Does JC virus have a role in the etiology and prognosis of Egyptian colorectal carcinoma?

John Cunningham virus (JCV) encodes an oncogenic T‐antigen, which is capable of interacting with key growth regulatory pathways. JCV definite role as causal agent of human cancer, still awaits final confirmation. The present study was conducted to assess the possible role of JCV in Egyptian colorectal carcinoma (CRC) and correlate the expression with the clinicopathological features and survival. JCV in situ hybridization (ISH) signals and large T antigen immunoreactivity were examined in 87 colonic specimens. Positive glandular JCV ISH signals were detected in 20%, 25% and 40% of normal, adenoma and CRC cases respectively. Stromal JCV ISH signals were identified in 26% of CRC cases and 5% of adenoma however, normal mucosa did not show stromal positivity with significant difference (p = 0.03). Glandular JCV expression was significantly associated with high grade (p = 0.03), high mitotic index (p=0.02) and low apoptotic index (p = 0.00). Positive stromal signals were significantly associated with low apoptosis (p = 0.00). No positive nuclear immunostaining of JCV large T antigen was detected in all specimens. JCV stromal expression was the 2nd most powerful indicator of short survival and bad prognosis (p = 0.03) in CRC patients. JCV might play an etiological role in CRC tumorogenesis and short survival in Egyptian CRC patients.     

Laser capture microdissection of cervical human papillomavirus infections: Copy number of the virus in cancerous and normal tissue and heterogeneous DNA methylation

Research on the pathogenicity of human papillomaviruses (HPVs) during cervical carcinogenesis often relies on the study of homogenized tissue or cultured cells. This approach does not detect molecular heterogeneities within the infected tissue. It is desirable to understand molecular properties in specific histological contexts. We asked whether laser capture microdissection (LCM) of archival cervical tumors in combination with real-time polymerase chain reaction and bisulfite sequencing permits (i) sensitive DNA diagnosis of small clusters of formalin-fixed cells, (ii) quantification of HPV DNA in neoplastic and normal cells, and (iii) analysis of HPV DNA methylation, a marker of tumor progression. We analyzed 26 tumors containing HPV-16 or 18. We prepared DNA from LCM dissected thin sections of 100 to 2000 cells, and analyzed aliquots corresponding to between nine and 70 cells. We detected nine to 630 HPV-16 genome copies and one to 111 HPV-18 genome copies per tumor cell, respectively. In 17 of the 26 samples, HPV DNA existed in histologically normal cells distant from the margins of the tumors, but at much lower concentrations than in the tumor, suggesting that HPVs can infect at low levels without pathogenic changes. Methylation of HPV DNA, a biomarker of integration of the virus into cellular DNA, could be measured only in few samples due to limited sensitivity, and indicated heterogeneous methylation patterns in small clusters of cancerous and normal cells. LCM is powerful to study molecular parameters of cervical HPV infections like copy number, latency and epigenetics.     

Neuroprotective efficacy of nimesulide against hippocampal neuronal damage following transient forebrain ischemia

Cyclooxygenase-2 is involved in the inflammatory component of the ischemic cascade, playing an important role in the delayed progression of the brain damage. The present study evaluated the pharmacological effects of the selective cyclooxygenase-2 inhibitor nimesulide on delayed neuronal death of hippocampal CA1 neurons following transient global cerebral ischemia in gerbils. Administration of therapeutically relevant doses of nimesulide (3, 6 and 12 mg/kg; i.p.) 30 min before ischemia and at 6, 12, 24, 48 and 72 h after ischemia significantly (P<0.01) reduced hippocampal neuronal damage. Treatment with a single dose of nimesulide given 30 min before ischemia also resulted in a significant increase in the number of healthy neurons in the hippocampal CA1 sector 7 days after ischemia. Of interest is the finding that nimesulide rescued CA1 pyramidal neurons from ischemic death even when treatment was delayed until 24 h after ischemia (34+/-9% protection). Neuroprotective effect of nimesulide is still evident 30 days after the ischemic episode, providing the first experimental evidence that cyclooxygenase-2 inhibitors confer a long-lasting neuroprotection. Oral administration of nimesulide was also able to significantly reduce brain damage, suggesting that protective effects are independent of the route of administration. The present study confirms the ability of cyclooxygenase-2 inhibitors to reduce brain damage induced by cerebral ischemia and indicates that nimesulide can provide protection when administered for up to 24 h post-ischemia.     

Prospective evaluation of plasma cortisol in recent trauma survivors with posttraumatic stress disorder

Hypothalamic pituitary adrenal axis abnormalities have been described in posttraumatic stress disorder (PTSD), and among the recently traumatized. Plasma cortisol and continuous measures of PTSD symptoms were obtained from 21 survivors, at 1 week and 6 months after traumatic events. Eight survivors met Clinician Administered PTSD Scale criteria for PTSD at 6 months. Cortisol levels at 1 week did not predict subsequent PTSD. Survivors with and without PTSD had similar mean levels of cortisol at both time points. Cortisol levels at 6 months negatively correlated with self-reported PTSD symptoms within PTSD subjects.     

Providers of primary care to homeless women in Los Angeles County

Little is known about the access barriers homeless women face at the sites where they are most likely to receive primary health care. To investigate this issue, we administered a mail survey to administrators and clinicians at clinic sites that were actual or potential providers of primary health care to homeless women in Los Angeles County in 1997. The response rate was 65%. Ninety percent of the homeless women seen by responding sites were seen at only 34% of those sites (designated as "major providers"). Deficiencies were identified in several structural and process characteristics that enhance access to and quality of care for homeless women, including clinician training in care for homeless persons; formal screening for homeless status and associated risk factors; and on-site provision of comprehensive health services, including mental health, substance abuse, reproductive health, and ancillary services. Some, but not all, deficiencies were less severe at major providers. Our results suggest that, although providers of care to homeless women share challenges faced by many safety net providers, there are several policy interventions that could improve access to and quality of care for homeless women.