Integrating postabortion care, menstrual regulation and family planning services in Bangladesh: a pre-post evaluation.

BACKGROUND: In Bangladesh, abortion is restricted except to save the life of a woman, but menstrual regulation is allowed to induce menstruation and return to non-pregnancy after a missed period. MR services are typically provided through the Directorate General of Family Planning, while postabortion care services for incomplete abortion are provided by facilities under the Directorate General of Health Services. The bifurcated health system results in reduced quality of care, particularly for postabortion care patients whose procedures are often performed using sub-optimal uterine evacuation technology and typically do not receive postabortion contraceptive services. This study evaluated the success of a pilot project that aimed to integrate menstrual regulation, postabortion care and family planning services across six Directorate General of Health Services and Directorate General of Family Planning facilities by training providers on woman-centered abortion care and adding family planning services at sites offering postabortion care. METHODS: A pre-post evaluation was conducted in the six large intervention facilities. Structured client exit interviews were administered to all uterine evacuation clients presenting in the 2-week data collection period for each facility at baseline (n = 105; December 2011-January 2012) and endline (n = 107; February-March 2013). Primary outcomes included service integration indicators such as provision of menstrual regulation, postabortion care and family planning services in both facility types, and quality of care indicators such as provision of pain management, provider communication and women's satisfaction with the services received. Outcomes were compared between baseline and endline for Directorate General of Family Planning and Directorate General of Health Services facilities, and chi-square tests and t-tests were used to test for differences between baseline and endline. RESULTS: At the end of the project there was an increase in menstrual regulation service provision in Directorate General of Health Services facilities, from none at baseline to 44.1% of uterine evacuation services at endline (p < 0.001). The proportion of women accepting a postabortion contraceptive method increased from 14.3% at baseline to 69.2% at endline in Directorate General of Health Services facilities (p = 0.006). Provider communication and women's rating of the care they received increased significantly in both Directorate General of Health Services and Directorate General of Family Planning facilities. CONCLUSIONS: Integration of menstrual regulation, postabortion care and family planning services is feasible in Bangladesh over a relatively short period of time. The intervention's focus on woman-centered abortion care also improved quality of care. This model can be scaled up through the public health system to ensure women's access to safe uterine evacuation services across all facility types in Bangladesh.

High-mobility group box-1 protein promotes granulomatous nephritis in adenine-induced nephropathy.

Granulomatous nephritis can be triggered by diverse factors and results in kidney failure. However, despite accumulating data about granulomatous inflammation, pathogenetic mechanisms in nephritis remain unclear. The DNA-binding high-mobility group box-1 protein (HMGB1) initiates and propagates inflammation when released by activated macrophages, and functions as an 'alarm cytokine' signaling tissue damage. In this study, we showed elevated HMGB1 expression in renal granulomas in rats with crystal-induced granulomatous nephritis caused by feeding an adenine-rich diet. HMGB1 levels were also raised in urine and serum, as well as in monocyte chemoattractant protein-1 (MCP-1), a mediator of granulomatous inflammation. Injection of HMGB1 worsened renal function and upregulated MCP-1 in rats with crystal-induced granulomatous nephritis. HMGB1 also induced MCP-1 secretion through mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase (PI3K) pathways in rat renal tubular epithelial cells in vitro. Hmgb1(+/-) mice with crystal-induced nephritis displayed reduced MCP-1 expression in the kidneys and in urine and the number of macrophages in the kidneys was significantly decreased. We conclude that HMGB1 is a new mediator involved in crystal-induced nephritis that amplifies granulomatous inflammation in a cycle where MCP-1 attracts activated macrophages, resulting in excessive and sustained HMGB1 release. HMGB1 could be a novel target for inhibiting chronic granulomatous diseases.

Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc.

High mobility group box-1 protein (HMGB1), primarily from the nucleus, is released into the extracellular milieu either passively from necrotic cells or actively through secretion by monocytes/macrophages. Extracellular HMGB1 acts as a potent inflammatory agent by promoting the release of cytokines such as tumor necrosis factor (TNF)-alpha, has procoagulant activity, and is involved in death due to sepsis. Accordingly, HMGB1 is an appropriate therapeutic target. In this study, we found that an extract of Prunus mume Sieb. et Zucc. (Ume) fruit (Ume extract), an abundant source of triterpenoids, strongly inhibited HMGB1 release from lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cells. The inhibitory effect on HMGB1 release was enhanced by authentic oleanolic acid (OA), a naturally occurring triterpenoid. Similarly, the HMGB1 release inhibitor in Ume extract was found to be OA. Regarding the mechanisms of the inhibition of HMGB1 release, the OA or Ume extract was found to activate the transcription factor Nrf2, which binds to the antioxidative responsive element, and subsequently the heme oxygenase (HO)-1 protein was induced, indicating that the inhibition of HMGB1 release from LPS-stimulated RAW264.7 cells was mediated via the Nrf2/HO-1 system; an essentially antioxidant effect. These results suggested that natural sources of triterpenoids warrant further evaluation as 'rescue' therapeutics for sepsis and other potentially fatal systemic inflammatory disorders.

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment.

High-mobility group box 1 (HMGB1) protein is a multifunctional protein, which is mainly present in the nucleus and is released extracellularly by dying cells and/or activated immune cells. Although extracellular HMGB1 is thought to be a typical danger signal of tissue damage and is implicated in diverse diseases, its relevance to ocular diseases is mostly unknown. To determine whether HMGB1 contributes to the pathogenesis of retinal detachment (RD), which involves photoreceptor degeneration, we investigated the expression and release of HMGB1 both in a retinal cell death induced by excessive oxidative stress in vitro and in a rat model of RD-induced photoreceptor degeneration in vivo. In addition, we assessed the vitreous concentrations of HMGB1 and monocyte chemoattractant protein 1 (MCP-1) in human eyes with RD. We also explored the chemotactic activity of recombinant HMGB1 in a human retinal pigment epithelial (RPE) cell line. The results show that the nuclear HMGB1 in the retinal cell is augmented by death stress and upregulation appears to be required for cell survival, whereas extracellular release of HMGB1 is evident not only in retinal cell death in vitro but also in the rat model of RD in vivo. Furthermore, the vitreous level of HMGB1 is significantly increased and is correlated with that of MCP-1 in human eyes with RD. Recombinant HMGB1 induced RPE cell migration through an extracellular signal-regulated kinase-dependent mechanism in vitro. Our findings suggest that HMGB1 is a crucial nuclear protein and is released as a danger signal of retinal tissue damage. Extracellular HMGB1 might be an important mediator in RD, potentially acting as a chemotactic factor for RPE cell migration that would lead to an ocular pathological wound-healing response.

Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells.

High mobility group box 1 (HMGB1) is a non-histone nuclear protein which is released from the nucleus of activated macrophages into the extracellular space in response to stimuli such as endotoxin or necrosis. The HMGB1 functions as a potent proinflammatory cytokine in the extracellular spaces. Recently, HMGB1 has been implicated in the progression of atherosclerosis. However, the association between HMGB1 and the development of atherosclerosis is poorly understood. Therefore, we examined whether serotonin (5-HT), a key factor involved in the development of atherosclerosis, induced HMGB1 release in human umbilical vein endothelial cells (HUVECs). We found that 5-HT induced the release of HMGB1 but not of ERK1/2 and JNK from HUVECs via the 5-HT receptor (5-HT1B)/p38 mitogen-activated protein kinase (MAPK) signaling pathway. The p38MAPK inhibitor SB203580 and the 5-HT1B antagonist GR55526 markedly inhibited HMGB1 release from 5-HT-stimulated HUVECs. The vascular endothelial growth factor (VEGF) derived from activated macrophages in atherosclerotic lesions also plays an important role in the progression of atherosclerosis. We found that HMGB1 induced VEGF production in macrophage-like RAW264.7 cells. HMGB1 induced the activation of p38MAPK, ERK1/2 and Akt. The PI3-kinase inhibitor LY294002 significantly inhibited VEGF production in HMGB1-stimulated macrophages, while other kinase inhibitors did not. These results suggest that HMGB1 release may contribute as a risk factor in the development and progression of atherosclerosis.

Photomorphogenesis of rice seedlings: a mutant impaired in phytochrome-mediated inhibition of coleoptile growth.

A mutant showing a long coleoptile phenotype under white light was isolated from gamma-ray-mutagenized rice (cv. Nihonmasari). This mutant, named cpm1 (coleoptile photomorphogenesis 1), has been found to be impaired in phytochrome-mediated inhibition of coleoptile growth. Another outstanding feature of the mutant is impaired anthesis. Under red light (R), cpm1 coleoptiles elongate at a higher rate than wild-type (WT) coleoptiles, owing to substantially reduced responsiveness to R. This phenotype occurs in an age-dependent manner, and cpm1 coleoptiles become responsive to R as they elongate. The impairment was found in both very-low-fluence and low-fluence responses. Mutant coleoptiles also elongate longer than WT coleoptiles in darkness, but in this case the long coleoptile results from an extended elongation period. The cpm1 mutation does not affect the following phytochrome responses: the growth stimulation in submerged coleoptiles (uncovered in this study), potentiation of greening, and down-regulation of PHYA transcription. The cpm1 mutation does not significantly affect the level of spectroscopically detectable phytochrome and the transcription levels of three phytochrome genes (PHYA-C). It is concluded that the CPM1 gene is involved in the phytochrome signal transduction that specifically leads to growth inhibition. Some aspects of rice seedling photomorphogenesis are discussed in relation to the results obtained.

Ebselen inhibits NO-induced apoptosis of differentiated PC12 cells via inhibition of ASK1-p38 MAPK-p53 and JNK signaling and activation of p44/42 MAPK and Bcl-2.

Ebselen, a selenium-containing heterocyclic compound, prevents ischemia-induced cell death. However, the molecular mechanism through which ebselen exerts its cytoprotective effect remains to be elucidated. Using sodium nitroprusside (SNP) as a nitric oxide (NO) donor, we show here that ebselen potently inhibits NO-induced apoptosis of differentiated PC12 cells. This was associated with inhibition of NO-induced phosphatidyl Serine exposure, cytochrome c release, and caspase-3 activation by ebselen. Analysis of key apoptotic regulators during NO-induced apoptosis of differentiated PC12 cells showed that ebselen blocks the activation of the apoptosis signaling-regulating kinase 1 (ASK1), and inhibits phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal protein kinase (JNK). Moreover, ebselen inhibits NO-induced p53 phosphorylation at Ser15 and c-Jun phosphorylation at Ser63 and Ser73. It appears that inhibition of p38 MAPK and p53 phosphorylation by ebselen occurs via a thiol-redox-dependent mechanism. Interestingly, ebselen also activates p44/42 MAPK, and inhibits the downregulation of the antiapoptotic protein Bcl-2 in SNP-treated PC12 cells. Together, these findings suggest that ebselen protects neuronal cells from NO cytotoxicity by reciprocally regulating the apoptotic and antiapoptotic signaling cascades.