Partial Protection from Metabolic Syndrome in Chronic Hepatitis C Elderly Subjects Due to Lower Triglyceride Level.

BACKGROUND: In Taiwan, persons over 65 years old have higher prevalence of hepatitis C. Among these patients, around 50% have non-alcoholic fatty liver disease (NAFLD). Since cardiovascular diseases and diabetes are main causes of death in this age group, in this cross-sectional study, we tried to evaluate the effects of NAFLD and hepatitis C on the risk of metabolic syndrome (MetS). METHODS: In total, 25 116 subjects over 65 years old who presented for routine health check-ups were enrolled. From the results of seropositivity for hepatitis C and abnormal echogenicity, they were classified into four groups: normal (N), subjects with only hepatitis C (C), subjects with only abnormal echogenicity (E) and subjects with both hepatitis C and abnormal echogenicity (CE). RESULTS: Subjects in both groups E and CE had higher abnormal MetS components than group C. Among all five components, triglyceride (TG) was the one having the highest odds ratio (OR) in determining the incidence of MetS in groups C and E. Finally, compared to group N, both groups E and CE had significantly higher OR for having MetS. However, after adjusting for confounding factors, only the significance between groups E and N remained. In other words, higher MetS was noted in group E compared to group N and there was no difference in incidence of MetS between group CE and group N. CONCLUSIONS: Chronic hepatitis C is a protective factor against having MetS and this effect might be due to lower TG level in the elderly. Further studies are warranted for the underlying mechanisms.

Erlotinib derivative inhibits hepatocellular carcinoma by targeting CIP2A to reactivate protein phosphatase 2A.

Protein phosphatase 2A (PP2A) is a tumor suppressor, which is functionally defective in various cancers. Previously, we found that PP2A activity determined the anticancer effect of bortezomib and erlotinib in hepatocellular carcinoma (HCC) cells. Here, we tested a novel erlotinib derivative, TD52, in four HCC cell lines, PLC5, Huh-7, Hep3B and Sk-Hep1. Using MTT and flow cytometry, we showed that TD52 had more potent apoptotic effects than erlotinib in HCC cells. TD52-induced apoptosis was associated with dose- and time- dependent reactivation of PP2A and downregulation of cancerous inhibitor of protein phosphatase 2A (CIP2A) and p-Akt. Inhibition of PP2A or ectopic expression of CIP2A or Akt in PLC5 cells abolished the effects of TD52. Furthermore, we demonstrated that TD52 affected the binding of Elk-1 to the proximal promoter of the CIP2A gene, thus downregulating transcription of CIP2A. Importantly, TD52-induced tumor inhibition was associated with reactivation of PP2A and downregulation of CIP2A and p-Akt in vivo. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A determines the apoptotic effect induced by TD52. Our findings disclose the therapeutic mechanism of this novel targeted agent, and suggest the therapeutic potential and feasibility of developing PP2A enhancers as a novel anticancer strategy.

Identification of B-cell epitope of dengue virus type 1 and its application in diagnosis of patients.

Using a serotype-specific monoclonal antibody (MAb) of dengue virus type 1 (DEN-1), 15F3-1, we identified the B-cell epitope of DEN-1 from a random peptide library displayed on phage. Fourteen immunopositive phage clones that bound specifically to MAb 15F3-1 were selected. These phage-borne peptides had a consensus motif of HxYaWb (a = S/T, b = K/H/R) that mimicked the sequence HKYSWK, which corresponded to amino acid residues 111 to 116 of the nonstructural protein 1 (NS1) of DEN-1. Among the four synthetic peptides corresponding to amino acid residues 110 to 117 of the NS1 of DEN-1, -2, -3, and -4, only one peptide, EHKYSWKS (P14M) of DEN-1, was found to bind to 15F3-1 specifically. Furthermore, P14M was shown to inhibit the binding of phage particles to 15F3-1 in a competitive inhibition assay. Histidine(111) (His(111)) was crucial to the binding of P14M to 15F3-1, since its binding activity dramatically reduced when it changed to leucine(111) (Leu(111)). This epitope-based peptide demonstrated its clinical diagnostic potential when it reacted with a high degree of specificity with serum samples obtained from both DEN-1-infected rabbits and patients. Based on these observations, our DEN-1 epitope-based serologic test could be useful in laboratory viral diagnosis and in understanding the pathogenesis of DEN-1.

X-linked agammaglobulinemia: a case report.

A 20-year-old male was admitted with fever and hemoptysis. Agammaglobulinemia was found, with bronchiectasis and sinusitis. Clinical and laboratory evidence included immunological examinations, bone marrow and small intestinal biopsies. Results suggested a diagnosis of X-linked agammaglobulinemia. After treatment with antibiotics and intravenous human immunoglobuline, the clinical symptoms demonstrated progressive improvement. The case is reported along with a review of the literature.

Biomechanical effect of a two-segment anterior cruciate ligament graft with separate femoral attachments and differing levels of prescribed load sharing.

The objective of this study was to analyze the biomechanical effect of varying the level of prescribed load sharing between two segments of an anterior cruciate ligament (ACL) graft, and of separating the femoral attachments of these segments. Total anterior-posterior (AP) laxity was measured using an instrumented spatial linkage. Forces in graft segments were measured using buckle transducers. The two-segment graft was formed using the middle third of the patellar tendon with bone blocks and a synthetic augmentation device. Proximal fixation was obtained using a fixture which allowed changing the individual locations of the femoral attachments of the tendon and augmentation segments. Distal fixation was achieved using a force-setting device which allowed the loads in each segment to be set to prescribed levels. Total graft force, load sharing, and total AP laxity were recorded during the application of 100-N AP tibial loads at 0 degrees, 30 degrees, 60 degrees, 90 degrees, and 110 degrees flexion, for various combinations of load sharing set at extension and locations of femoral attachment sites. The load sharing, total graft force, and AP laxity during AP loading at the five test flexion angles were not significantly affected by changing the prescribed level of load sharing set at extension for a given femoral attachment configuration. However, varying the separate hole locations of the graft segments for a given level of load sharing significantly affected load sharing, total graft force, and AP laxity. If the tendon graft was located posteriorly (on the medial surface of the lateral femoral condyle) and the augmentation segment proximally, the augmentation carried a greater portion of the total force in flexion. If the augmentation segment was changed to a more posterosuperior location and the tendon posteroinferior, the tendon carried a higher percentage of the total force in flexion. AP laxity in most reconstruction states was significantly greater than in the normal joint with an intact ACL. The nature of the load sharing between the graft segments under AP tibial load over the flexion range can be controlled by the appropriate choice of the segments' femoral attachment locations.

Determination of gold, indium, tellurium and thallium in the same sample digest of geological materials by atomic-absorption spectroscopy and two-step solvent extraction.

A rock, soil, or stream-sediment sample is decomposed with hydrofluoric acid, aqua regia, and hydrobromic acid-bromine solution. Gold, thallium, indium and tellurium are separated and concentrated from the sample digest by a two-step MIBK extraction at two concentrations of hydrobromic add. Gold and thallium are first extracted from 0.1M hydrobromic acid medium, then indium and tellurium are extracted from 3M hydrobromic acid in the presence of ascorbic acid to eliminate iron interference. The elements are then determined by flame atomic-absorption spectrophotometry. The two-step solvent extraction can also be used in conjunction with electrothermal atomic-absorption methods to lower the detection limits for all four metals in geological materials.

Removal of iron interferences by solvent extraction for geochemical analysis by atomic-absorption spectrophotometry.

Iron is a common interferent in the determination of many elements in geochemical samples. Two approaches for its removal have been taken. The first involves removal of iron by extraction with methyl isobutyl ketone (MIBK) from hydrochloric acid medium, leaving the analytes in the aqueous phase. The second consists of reduction of iron(III) to iron(II) by ascorbic acid to minimize its extraction into MIBK, so that the analytes may be isolated by extraction. Elements of interest can then be determined using the aqueous solution or the organic extract, as appropriate. Operating factors such as the concentration of hydrochloric acid, amounts of iron present, number of extractions, the presence or absence of a salting-out agent, and the optimum ratio of ascorbic acid to iron have been determined. These factors have general applications in geochemical analysis by atomic-absorption spectrophotometry.

Determination of total tin in geological materials by electrothermal atomic-absorption spectrophotometry using a tungsten-impregnated graphite furnace.

An electrothermal atomic-absorption spectrophotometric method is described for the determination of total tin in geological materials, with use of a tungsten-impregnated graphite furnace. The sample is decomposed by fusion with lithium metaborate and the melt is dissolved in 10% hydrochloric acid. Tin is then extracted into trioctylphosphine oxide-methyl isobutyl ketone prior to atomization. Impregnation of the furnace with a sodium tungstate solution increases the sensitivity of the determination and improves the precision of the results. The limits of determination are 0.5-20 ppm of tin in the sample. Higher tin values can be determined by dilution of the extract. Replicate analyses of eighteen geological reference samples with diverse matrices gave relative standard deviations ranging from 2.0 to 10.8% with an average of 4.6%. Average tin values for reference samples were in general agreement with, but more precise than, those reported by others. Apparent recoveries of tin added to various samples ranged from 95 to 111% with an average of 102%.

Matrix effects on the determination of manganese in geological materials by atomic-absorption spectrophotometry under different flame conditions.

Suppression caused by five of the seven matrix elements studied (Si, Al, Fe, Ca and Mg) was observed in the atomic-absorption determination of manganese in geological materials, when synthetic solutions and the recommended oxidizing air-acetylene flame were used. The magnitude of the suppression effects depends on (1) the kind and concentration of the interfering elements, (2) the type of acid medium, and (3) the concentration of manganese to be determined. All interferences noted are removed or alleviated by using a reducing nitrous oxide-acetylene flame. The atomic-absorption method using this flame can be applied to the determination of total and extractable manganese in a wide range of geological materials without interferences. Analyses of six U.S. Geological Survey rock standards for manganese gave results in agreement with the reported values.

Ultrastructural alterations in skeletal muscle fibers of streptozotocin-diabetic rats.

The ultrastructure of fast-twitch-oxidative-glycolytic (FOG), fast-twitch-glycolytic (FG) and slow-twitch-oxidative (SO) fibers in plantaris and soleus muscles of normal and streptozotocin-diabetic rats was studied. In the diabetic animals, the mitochondria of FOG and SO fibers showed a loss of cristae and an increase in electron-dense granules. There was also an increased number of lipid droplets in close proximity to the mitochondria and the nuclei, and a separation of individual muscle nuclei to form satellite cells. Higher incidences of surface projections and sarcoplasmic splittings at the nuclear region were noticed in SO fibers. The FG fibers showed some disorientation of the T-tubular system. It is concluded that streptozotocin-diabetes has differential effects on the fine structure of the three fiber types of rat skeletal muscle.