Alcohol and hepatitis C mortality among males and females in the United States: a life table analysis

OBJECTIVE: Evidence from previous studies suggests that heavy alcohol use (HAU) exacerbates the rate of fibrosis progression in the liver and results in increased probability for premature death among patients with hepatitis C virus (HCV) infection. The current study uses population-based mortality data to investigate whether heavy drinking affects the age of death among individuals with HCV and, if so, whether this effect differs between men and women. METHODS: A total of 7,263,163 death records in the United States between 2000 and 2002 were drawn from the Multiple Cause of Death (MCD) public-use data files compiled by the National Center for Health Statistics (NCHS). International Classification of Diseases, Tenth Revision (ICD-10) codes were used to identify the presence of HCV (B17.1 and B18.2) and HAU (as indicated by alcohol-induced medical conditions, F10 and K70) either as the underlying cause or as one of the contributing causes of death. The deaths were divided into 4 distinctive cause-of-death categories: HCV without HAU, HAU without HCV, HCV plus HAU, and all others. The mean ages of death and the cumulative probabilities of death derived from multiple-cause life table were compared across these categories. RESULTS: Hepatitis C virus deaths showed an excessive prevalence of HAU when compared with non-HCV deaths. Compared with deaths of HCV without HAU, the mean age of death was shortened for deaths of HCV plus HAU (from 55.1 to 50.0 years among males, and from 61.0 to 49.1 years among females). The cumulative probability of death before age 65 was much higher for the latter than the former group (0.91 vs 0.68 among males, and 0.88 vs 0.47 among females). While HCV alone showed a disproportionate effect on premature death in males, HAU presented a stronger effect in females, resulting in a "catching-up" effect that diminished the gender difference in age of HCV death. CONCLUSIONS: This study provides mortality-based evidence to further establish heavy alcohol consumption as one of the key risk factors contributing to premature deaths from HCV in the United States. More importantly, this study, for the first time, presents empirical evidence that alcohol consumption affects men and women differently in HCV mortality.     

Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores

Peroxisome proliferator-activated receptor-γ (PPARγ) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPARγ agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.     

Analysis of clinical outcomes of patients with adenoid cystic carcinoma of Bartholin glands

Adenoid cystic carcinoma of Bartholin glands (BG-ACC) is a rare, slow-growing but a highly aggressive tumor with remarkable capacity for local recurrence and distant metastasis. The purpose of this study was to elucidate our experiences of the diagnosis and treatment of BG-ACC and to analyze the clinical outcomes and prognosis of patients with BG-ACC. A retrospective chart review was performed to assess the demographic information, chief complaints, pathologic features of tumors, primary treatment, and development of local recurrence or distant metastasis, as well as the patient outcome. All patients received surgical excision as the primary treatment, and the diagnosis of BG-ACC was confirmed histopathologically. Three of four patients whose tumors showed pathologic features indicating a high probability of recurrence received adjuvant radiotherapy. These patients did not develop local recurrence, in contrast, one patient who did not receive adjuvant radiotherapy developed local recurrence and distant metastasis on several occasions. All patients who received primary surgical treatment are alive to date. When patients who are more than 40 years of age and who present with symptomatic BG lesions, BG-ACC should be included in the differential diagnosis and biopsy should be performed for histopathologic confirmation. Radical local excision with sufficient negative margins seems to be beneficial for primary treatment. Adjuvant radiotherapy is a reasonable treatment option for patients with high risk factors after surgery or for patients who develop local recurrence.     

The Cyclic Peptide Ecumicin Targeting ClpC1 Is Active against Mycobacterium tuberculosis In Vivo

Drug-resistant tuberculosis (TB) has lent urgency to finding new drug leads with novel modes of action. A high-throughput screening campaign of >65,000 actinomycete extracts for inhibition of Mycobacterium tuberculosis viability identified ecumicin, a macrocyclic tridecapeptide that exerts potent, selective bactericidal activity against M. tuberculosis in vitro, including nonreplicating cells. Ecumicin retains activity against isolated multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis. The subcutaneous administration to mice of ecumicin in a micellar formulation at 20 mg/kg body weight resulted in plasma and lung exposures exceeding the MIC. Complete inhibition of M. tuberculosis growth in the lungs of mice was achieved following 12 doses at 20 or 32 mg/kg. Genome mining of lab-generated, spontaneous ecumicin-resistant M. tuberculosis strains identified the ClpC1 ATPase complex as the putative target, and this was confirmed by a drug affinity response test. ClpC1 functions in protein breakdown with the ClpP1P2 protease complex. Ecumicin markedly enhanced the ATPase activity of wild-type (WT) ClpC1 but prevented activation of proteolysis by ClpC1. Less stimulation was observed with ClpC1 from ecumicin-resistant mutants. Thus, ClpC1 is a valid drug target against M. tuberculosis, and ecumicin may serve as a lead compound for anti-TB drug development.     

Accuracy of Diffusion Tensor Imaging for Diagnosing Cervical Spondylotic Myelopathy in Patients Showing Spinal Cord Compression

ObjectiveTo assess the performance of diffusion tensor imaging (DTI) for the diagnosis of cervical spondylotic myelopathy (CSM) in patients with deformed spinal cord but otherwise unremarkable conventional magnetic resonance imaging (MRI) findings.ResultsThe MD, LD, and RD cut-off values were 1.079 × 10^-3, 1.719 × 10^-3, and 0.749 × 10^-3 mm²/sec, respectively, and that of FA was 0.475. Sensitivity, specificity, positive predictive value and negative predictive value were: 100 (4/4), 44.8 (13/29), 20 (4/20), and 100 (13/13) for MD; 100 (4/4), 27.6 (8/29), 16 (4/25), and 100 (8/8) for FA; 100 (4/4), 58.6 (17/29), 25 (4/16), and 100 (17/17) for MD∩FA; 100 (4/4), 68.9 (20/29), 30.8 (4/13), and 100 (20/20) for LD∩FA; and 75 (3/4), 68.9 (20/29), 25 (3/12), and 95.2 (20/21) for RD∩FA in percentage value. Diagnostic performance comparisons revealed significant differences only in specificity between FA and MD∩FA (p = 0.003), FA and LD∩FA (p < 0.001), FA and RD∩FA (p < 0.001), MD and LD∩FA (p = 0.024) and MD and RD∩FA (p = 0.024).ConclusionFractional anisotropy combined with MD, RD, or LD is expected to be more useful than FA and MD for diagnosing CSM in patients who show deformed spinal cords without signal changes on MRI.     

Bone Tunnel Diameter Measured with CT after Anterior Cruciate Ligament Reconstruction Using Double-Bundle Auto-Hamstring Tendons: Clinical Implications

ObjectiveTo evaluate the correlation between bone tunnel diameter after anterior cruciate ligament (ACL) reconstruction measured by computed tomography (CT) using multiplanar reconstruction (MPR) and stability or clinical scores.ResultsThe tibial bone tunnels for the anteromedial bundles were significantly widened at T2 compared with T1 (observer 1, 0.578 mm to 0.698 mm, p value of < 0.001; observer 2, 0.581 mm to 0.707 mm, p value of < 0.001). There was no significant correlation between the diameter at T2 and stability or clinical scores and between the interval change ratio ([T2 - T1] / T1) and stability or clinical scores (corrected p values for all were 1.0). Intraobserver agreement for measurements was excellent (> 0.8) for both observers. Interobserver agreement for measurement was excellent (> 0.8) except for the most distal portion of the femoral bone tunnel for anterior medial bundle in immediate postoperative CT, which showed moderate agreement (concordance correlation coefficient = 0.6311).ConclusionNeither the diameter nor its change ratio during interval follow-up is correlated with stability or clinical scores.     

Different expression patterns of lysosomal proteins exposed to melanin in HeLa cells

As a high quantity of melanin can lead to hyperpig­mentation or skin cancer in humans and it can also activate lysosomal enzymes so in the present study the changes in lysosomal enzymes upon exposure of HeLa cells to melanin has been studied. The HeLa cells were exposed to 100 ppm melanin for 24 hours and lysosomal enzymes were extracted. The lysosomal enzymes were identified through two­dimensional polyacrylamide gel electrophoresis (2­DE) after exposure of HeLa cells to melanin. The results showed 12 up­ and 3­down regulation spots in relation to melanin exposure. It has been observed that lysosomal proteins are related to melanin to decrease the color and quantity through cellular activation of lysosomes.