The emerging role of mast cells in liver disease.

The depth of our knowledge regarding mast cells has widened exponentially in the last 20 years. Once thought to be only important for allergy-mediated events, mast cells are now recognized to be important regulators of a number of pathological processes. The revelation that mast cells can influence organs, tissues, and cells has increased interest in mast cell research during liver disease. The purpose of this review is to refresh the reader's knowledge of the development, type, and location of mast cells and to review recent work that demonstrates the role of hepatic mast cells during diseased states. This review focuses primarily on liver diseases and mast cells during autoimmune disease, hepatitis, fatty liver disease, liver cancer, and aging in the liver. Overall, these studies demonstrate the potential role of mast cells in disease progression.

HIV-1 reverse transcriptase drug-resistance mutations in chronically infected individuals receiving or naïve to HAART in Cameroon.

The most common first-line, highly active anti-retroviral therapy (HAART) received by individuals infected with HIV-1 in Cameroon is the combination therapy Triomune, comprised of two nucleoside reverse transcriptase inhibitors (NRTI) and one non-NRTI (NNRTI). To examine the efficacy of these drugs in Cameroon, where diverse non-B HIV-1 subtypes and recombinant viruses predominate, the reverse transcriptase (RT) viral sequences in patient plasma were analyzed for the presence of mutations that confer drug resistance. Forty-nine HIV-1-positive individuals were randomly selected from those receiving care in HIV/AIDS outpatient clinics in the South-West and North-West Regions of Cameroon. Among the 28 patients receiving HAART, 39% (11/28) had resistance to NRTIs, and 46% (13/28) to NNRTIs after a median of 12 months from the start of therapy. Among those with drug-resistance mutations, there was a median of 14 months from the start of HAART, versus 9 months for those without; no difference was observed in the average viral load (10,997 copies/ml vs. 8,056 copies/ml). In contrast, drug-naïve individuals had a significantly higher average viral load (27,929 copies/ml) than those receiving HAART (9,527 copies/ml). Strikingly, among the 21 drug-naïve individuals, 24% harbored viruses with drug-resistance mutations, suggesting that HIV-1 drug-resistant variants are being transmitted in Cameroon. Given the high frequency of resistance mutations among those on first-line HAART, coupled with the high prevalence of HIV-1 variants with drug-resistance mutations among drug-naïve individuals, this study emphasizes the need for extensive monitoring of resistance mutations and the introduction of a second-line HAART strategy in Cameroon.

Pioglitazone inhibits connective tissue growth factor expression in advanced atherosclerotic plaques in low-density lipoprotein receptor-deficient mice.

Connective tissue growth factor (CTGF) is expressed in atherosclerotic plaques. It is generally recognized that CTGF contributes to atherosclerosis by stimulating vascular smooth muscle cell (VSMC) proliferation and extracellular matrix production during the development of atherosclerosis. Recent studies indicate that CTGF may also contribute to plaque destabilization as it induces apoptosis and stimulates MMP-2 expression in VSMCs. Thiazolidinediones (TZDs), a new class of insulin sensitizing drugs for type 2 diabetes, inhibit atherosclerosis. However, their effect on CTGF expression in atherosclerotic plaques remains unknown. In this study, male LDL receptor-deficient mice were fed high-fat diet for 4 months to induce the formation of atherosclerotic plaques and then given the high-fat diet with or without pioglitazone for the next 3 months. At the end of the 7-month study, CTGF expression in aortic atherosclerotic lesions was examined. Results showed that CTGF expression was increased in mice fed the high-fat diet by seven-fold as compared to that in mice fed normal chow, but the treatment with pioglitazone significantly inhibited the high-fat diet-induced CTGF expression. To verify these in vivo observations, in vitro studies using human aortic SMC were conducted. Quantitative real-time PCR and Western blot showed that pioglitazone inhibited TGF-beta-stimulated CTGF expression. In conclusion, the present study has demonstrated that pioglitazone inhibits CTGF expression in mouse advanced atherosclerotic plaques and in cultured human SMCs, and hence unveiled a possible mechanism potentially involved in the inhibition of atherosclerosis by TZD.

Antireflux surgery preserves lung function in patients with gastroesophageal reflux disease and end-stage lung disease before and after lung transplantation.

BACKGROUND: Gastroesophageal reflux disease (GERD) is common in patients with end-stage lung disease (ESLD). GERD may cause obliterative bronchiolitis after lung transplantation (LTx), represented by a decline in forced expiratory volume in 1 second (FEV(1)). OBJECTIVES: To identify the patterns of reflux in patients with ESLD and to determine whether antireflux surgery (ARS) positively impacts lung function. DESIGN: Retrospective review of prospectively collected data. SETTING: Tertiary care university hospital. PATIENTS: Forty-three patients with ESLD and documented GERD (pre-LTx, 19; post-LTx, 24). INTERVENTIONS: Antireflux surgery. MAIN OUTCOME MEASURES: Reflux patterns including laryngopharyngeal reflux as measured by esophageal impedance, and FEV(1), and episodes of pneumonia and acute rejection before and after ARS. RESULTS: Before ARS, 19 of 43 patients (44%) were minimally symptomatic or asymptomatic. Laryngopharyngeal reflux events, which occurred primarily in the upright position, were common in post-LTx (56%) and pre-LTx (31%) patients. At 1 year after ARS, FEV(1) significantly improved in 91% of the post-LTx patients (P < .01) and 85% of the pre-LTx patients (P = .02). Of patients with pre-ARS declining FEV(1), 92% of post-LTx and 88% of pre-LTx patients had a reversal of this trend. Episodes of pneumonia and acute rejection were significantly reduced in post-LTx patients (P = .03) or stablilized in pre-LTx patients (P = .09). CONCLUSIONS: There should be a low threshold for performing objective esophageal testing including esophageal impedance because GERD may be occult and ARS may improve or prolong allograft and native lung function.