NK and NKT-like cells in granulomatous and fibrotic lung diseases

Clinical and Experimental Medicine - Background The pathogenetic and regulatory roles of natural killer (NK) and natural killer T-like cells in interstitial lung diseases (ILDs), fibrotic and...     

Iron mediates production of a neutrophil chemoattractant by rat hepatocytes metabolizing ethanol.

Ethanol metabolism in hepatocytes is accompanied by release of a potent lipid chemoattractant for neutrophils. Production of the factor may initiate the inflammation associated with alcoholic hepatitis. In previous studies with a cytosol system from liver, production was blocked by iron chelators as well as by catalase and superoxide dismutase, suggesting the involvement of oxyradicals in formation of the chemoattractant. These studies have examined the role of iron in intact hepatocytes using cells from rats fed an iron-deficient diet, a control diet or a diet containing 3% carbonyl iron. The iron content averaged 1.4 nmol/mg protein in iron-deficient cells, 6.3 in controls and 135.3 in iron-loaded cells. Hepatocytes from all groups were established in primary culture and incubated with ethanol (10 mM); the medium was assayed for chemoattractant activity for human neutrophils. Cultures from chow-fed or iron-loaded animals produced chemoattractant as previously reported. By contrast, chemoattractant production was undetectable in the iron-deficient cultures. Addition of ferric citrate (10 microM) restored chemoattractant production while increasing cellular iron in the deficient cells less than 50% (to 2.3 nmol/mg protein). Addition of desferrioxamine mesylate to cultures of iron-loaded cells ablated chemoattractant production. The data provide evidence for the importance of hepatocellular iron in production of this alcohol-related lipid chemoattractant and suggest that a small intracellular pool of "free" iron plays a critical role.     

TWEAK induces liver progenitor cell proliferation

Progenitor ("oval") cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors.     

Integrating tuberculosis and HIV services in rural Kenya: uptake and outcomes

Setting: Seventeen rural public health facilities in Western Kenya that introduced three models of integrated care for tuberculosis (TB) and human immunodeficiency virus (HIV) patients.Objective: To assess the uptake and timing of cotrimoxazole preventive therapy (CPT) and antiretroviral treatment (ART) as well as anti-tuberculosis treatment outcomes among HIV-infected TB patients before (March–October 2010) and after (March–October 2012) the introduction of integrated TB-HIV care.Design: A before-and-after cohort study using programme data.Results: Of 501 HIV-infected TB patients, 357 (71%) were initiated on CPT and 178 (39%) on ART in the period before the introduction of integrated TB-HIV care. Following the integration of services, respectively 316 (98%) and 196 (61%) of 323 HIV-infected individuals were initiated on CPT and on ART (P < 0.001). The median time to CPT and ART initiation dropped from 7 to 2 days and from 42 to 34 days during the pre- and post-integration phases, respectively. Overall TB success rates did not vary with integration or with type of model instituted.Conclusion: Integration of TB and HIV services enhanced uptake and reduced delay in instituting CPT and ART in rural health facilities. There is a need to increase impetus in these efforts.     

Antenatal care and pregnancy outcomes in a safe motherhood health voucher system in rural Kenya, 2007–2013

Setting: A rural private health facility, Ruby Medical Centre (RMC), participating in a safe motherhood health voucher system for poor women in Kiambu County, Kenya.Objectives: Between 2007 and 2013, to determine 1) the number of women who delivered at the RMC, their characteristics and pregnancy-related outcomes, and 2) the number of women who received an incomplete antenatal care (ANC) package and associated factors.Design: Retrospective cross-sectional study using routine programme data.Results: During the study period, 2635 women delivered at the RMC: 50% were aged 16–24 years, 60% transferred in from other facilities and 59% started ANC in the third trimester of pregnancy. Of the 2635 women, 1793 (68%) received an incomplete ANC package: 347 (13%) missed essential blood tests, 312 (12%) missed the tetanus toxoid immunisation and 1672 (65%) had fewer than four visits. Presenting late and starting ANC elsewhere were associated with an incomplete package. One pregnancy-related mortality occurred; the stillbirth rate was 10 per 1000 births.Conclusion: This first assessment of the health voucher system in rural Kenya showed problems in ANC quality. Despite favourable pregnancy-related outcomes, increased efforts should be made to ensure earlier presentation of pregnant women, comprehensive ANC, and more consistent and accurate monitoring of reproductive indicators and interventions.     

Reduction in transmission of hepatitis C after the introduction of a heat-treatment step in the production of C1-inhibitor concentrate

BACKGROUND: The transmission of viral infections via protein concentrates made from a large pool of plasma depends on the selection of donors, fractionation process, and virucidal methods. To date, no data are available on the infectivity risk of plasma concentrates of the inhibitor of the first component of complement (C1-INH). STUDY DESIGN AND METHODS: The prevalence of blood-borne viral infections and levels of transaminases were evaluated in patients treated with a large- pool plasma concentrate of the inhibitor of C1-INH before and after the introduction of virucidal methods. The study included 85 patients with hereditary angioedema and 4 with acquired angioedema. The patients were divided into three groups: 1) 48 untreated patients; 2) 22 patients treated with non-virus-inactivated C1-INH concentrates; and 3) 19 patients treated with virus-inactivated concentrates. Serum samples obtained at various times after the infusion of concentrate were assayed for alanine amino-transferase and tested for hepatitis B surface antigen and antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (anti-HIV); anti-HCV-negative subjects exposed to the concentrate were also tested for HCV RNA. RESULTS: Prevalences of HCV infection and elevated alanine aminotransferase are significantly lower in patients treated with virus-inactivated concentrates than in those exposed to non-virus-inactivated concentrates. No patients were anti-HIV positive. CONCLUSION: This study suggests that C1-INH concentrates transmitted HCV, but that the virucidal methods adopted are effective in reducing the infectivity.