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Objective: To investigate the long-term incidence and predictors for hepatitis B surface antigen (HBsAg) loss after nucleoside analogue therapy., Methods: The study included 411 noncirrhotic chronic hepatitis B patients (148 hepatitis B e antigen (HBeAg)-positive and 263 HBeAg-negative patients) who were treated with lamivudine (n = 110) or entecavir (n = 301) with posttreatment follow-up of at least 12 months., Results: In HBeAg-positive patients, the 8-year cumulative rates of virologic relapse, clinical relapse and HBsAg loss were 55.6%, 47.7% and 19.6%, respectively. In HBeAg-negative patients, the rates were 69.3%, 58.9% and 33.1%, respectively. Cox regression analysis showed that hepatitis B virus genotype C and lower end-of-treatment HBsAg levels were independent predictors of HBsAg loss in HBeAg-positive and -negative patients. The 5-year HBsAg loss rate was 47.3% in HBeAg-positive patients with end-of-treatment HBsAg levels <300 IU/mL, while the 8-year HBsAg loss rate was 69.3% in HBeAg-negative patients with end-of-treatment HBsAg levels <200 IU/mL. Five patients experienced hepatitis flares with decompensation after stopping nucleoside analogue therapy, and one died after retreatment. Of the 48 patients who developed off-therapy HBsAg loss, two developed hepatocellular carcinoma., Conclusions: The rate of HBsAg loss was relatively high and the rate of hepatic events was low in noncirrhotic patients who discontinued nucleoside analogue therapy., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aims of this study are to compare the long-term efficacy and safety of entecavir and tenofovir in nucleos(t)ide analogue (NA)-naive patients with chronic hepatitis B (CHB) with high hepatitis B virus (HBV) DNA (> 6 log 10  IU/mL)., Methods: We recruited 419 NA-naive patients for analysis (313 entecavir, 106 tenofovir). We used propensity-score matching to match 106 patients in the tenofovir group with 212 patients in the entecavir group by age, baseline HBV DNA levels and cirrhosis after subgrouping by hepatitis B e antigen (HBeAg) status., Results: There was no significant difference in 3-year cumulative rates of virological response (VR) (96.4% versus 92.1%, p 0.26 in HBeAg-positive or 98.2% versus 98.6%, p 0.64 in HBeAg-negative patients), HBeAg loss (53.8% versus 47.4%, p 0.89) or seroconversion (40.2% versus 41.3%, p 0.77), and hepatocellular carcinoma (HCC) development (4% versus 2.7%, p 0.55) between the tenofovir and entecavir groups in either cohort or propensity-score matching patients. In subgroup analysis of patients with HBV DNA >10 8  IU/mL, entecavir and tenofovir showed similar effectiveness in achieving VR (90.9% versus 87.7% at 3 years; p 0.13). Tenofovir and diabetes mellitus were independent factors for acute kidney injury during treatment. Multivariate analysis showed that HBeAg-negative status, and lower baseline HBV DNA and HBV surface antigen levels were independent factors for achieving VR. Older age, lower baseline HBV DNA levels, cirrhosis and α-fetoprotein ≥8 ng/mL at 12 months of treatment were independently associated with HCC development., Conclusions: Tenofovir and entecavir have similar effectiveness in NA-naive CHB patients with high viraemia. Tenofovir might have a higher incidence of acute kidney injury compared with entecavir during treatment., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

There are limited data comparing the clinical outcomes between telbivudine and entecavir. We consecutively enrolled 115 telbivudine-naive and 115 entecavir-naive chronic hepatitis B patients, who were matched for age, sex, hepatitis B e antigen (HBeAg) status and cirrhosis, and treated for at least 2 years or less than 2 years but had developed resistance. Except for the rate of HBeAg seroconversion, which was similar, patients in the entecavir group had better clinical outcomes than those in the telbivudine group for alanine aminotransferase normalization (85.2% vs 78.4%, p <0.048), undetectable HBV DNA (96.5% vs 74.8%, p <0.001), and viral resistance (0.9% vs 21.7%, p <0.001) after 2 years of treatment, After applying roadmap or super-responders concepts, entecavir still had better outcomes than telbivudine in undetectable HBV DNA and viral resistance. The cumulative incidence of hepatocellular carcinoma development was similar between telbivudine-naive and entecavir-naive patients (p 0.565). In renal function analysis, there were significantly more patients with estimated glomerular filtration rate (eGFR) category improvement in both the telbivudine and entecavir groups at year 1 (p 0.006 and p 0.047, respectively). The rate of virological improvement was significantly higher with entecavir than with telbivudine after 2 years of treatment, whether applying the concepts of roadmap or super-responders. The incidence of hepatocellular carcinoma was similar between telbivudine and entecavir. Both telbivudine and entecavir were associated with eGFR improvement, especially in patients with renal insufficiency., (© 2013 The Authors Clinical Microbiology and Infection ©2013 European Society of Clinical Microbiology and Infectious Diseases.)

Background: Aspirin has received increasing attention owing to its potential as a chemopreventive agent against lung cancer. Previous observational studies have reported inconsistent findings on this issue. We investigated the association between aspirin use and risk for lung cancer by conducting a meta-analysis., Patients and Methods: Relevant studies were identified by searching Medline, EMBASE, and Cochrane Library to December 2009. We also reviewed relevant bibliographies from the retrieved articles. Two authors independently extracted data and assessed study quality. Disagreements were resolved by consensus., Results: Fifteen studies (six case-control studies and nine prospective cohort studies) were included in the final meta-analysis. When all studies were pooled, the odds ratio (OR) of aspirin use for lung cancer risk was 0.86 [95% confidence interval (CI) 0.76-0.98]. In subgroup meta-analyses, there was no association between aspirin use and lung cancer risk among cohort studies (relative risk, 0.97; 95% CI 0.87-1.08), while there was a significant association among case-control studies (OR, 0.74; 95% CI 0.57-0.99). In a subgroup meta-analysis by quality of study methodology, a significant protective effect of aspirin use on lung cancer was observed only among eight low-quality studies (OR, 0.82; 95% CI 0.68-0.99), but not among seven high-quality studies (OR, 0.90; 95% CI 0.76-1.07)., Conclusions: Overall, the findings of this meta-analysis support that there was no association between aspirin use and lung cancer risk. Our findings should be confirmed in future prospective cohort studies or randomized, controlled trials.

Background: Combinations of Child-Pugh classification and Liver Cancer Study Group of Japan/Tumor-Node-Metastasis (LCSGJ/TNM) have been reported as Japan Integrated Staging (JIS). We previously modified the 6th AJCC/TNM to serve as a better staging system than the 5th and 6th AJCC/TNM., Aims: To develop a modified TNM-based JIS to predict the survival of hepatocellular carcinoma (HCC) patients more accurately., Methods: 3764 HCC patients were enrolled from 1986 to 2002 (2882 patients from 1986 to 2000 and 882 patients from 2001 to 2002). We compared the performance of original JIS, modified TNM-based JIS, modified TNM-based JIS combined alpha-fetoprotein (AFP), BCLC, and CLIP. Lower Akaike information criteria (AIC) values indicated better discriminatory abilities., Results: AIC value was lowest in CLIP during all periods. However, during 2001-2002, when early-stage HCC patients were predominant, AIC value was lowest when modified TNM-based JIS combined AFP was used., Conclusion: The CLIP system provided the best prognostic stratification in the present cohort of HCC patients who were mainly at late stages. However, early detection of HCCs has become more common in Taiwan in recent years, which has led to the predominance of early-stage HCC patients. Therefore, modified TNM-based JIS combined AFP may now be the most applicable system in recent years.

Acinetobacter baumannii has emerged as a serious cause of nosocomial infections. Rapid identification of this pathogen is required so that appropriate therapy can be given and outbreaks controlled. This study evaluated a multiplex PCR and an automated ribotyping system for the rapid identification of Acinetobacter baumannii. In total, 22 different reference strains and 138 clinical isolates of Acinetobacter spp., identified by 16S-23S rRNA intergenic spacer (ITS) sequence analysis, were evaluated. All A. baumannii isolates (82 clinical isolates and one reference strain) were identified by the multiplex PCR method (specificity 100%). The sensitivity and specificity of the ribotyping system for identification of A. baumannii were 85.5% (71/83) and 93.5% (72/77), respectively. An additional 100 clinical isolates belonging to the Acinetobacter calcoaceticus-A. baumannii complex were used to compare these two methods for identification of A. baumannii, and this comparison revealed a level of disagreement of 14% (14 isolates). The accuracy of the multiplex PCR was 100%, which was confirmed by sequence analysis of the ITS and recA gene of these isolates. Thus, the multiplex PCR method dramatically increased the efficiency and speed of A. baumannii identification.

Current dietary guidelines recommend a decrease in fat intake and an increase in fiber consumption. Decreased bioavailability (BV) of carotenoids is thought to be associated with both of these recommendations. A 2 x 4 factorial design was used to test the effects of dietary fat level at 10 or 30% of total energy and fiber type using no fiber, silica, citrus pectin or oat gum (7 g/100 g) on beta-carotene (betaC) BV in 4- to 5-wk-old Mongolian gerbils. We assessed BV as both accumulation of betaC and bioconversion of betaC to vitamin A (VA) in tissues. A VA- and betaC-deficient diet was fed for 1 wk followed by one of eight isocaloric, semipurified diets supplemented with carrot powder [ approximately 1 microgram betaC, 0.5 microgram alpha-carotene (alphaC)/kJ diet] for 2 wk (n = 12/group). Increasing dietary fat resulted in higher VA (P: = 0.074) and lower betaC (P: = 0.0001) stores in the liver, suggesting that consumption of high fat diets enhances conversion of betaC to VA. The effect of soluble fiber on hepatic VA storage was dependent on fiber type. Consumption of citrus pectin resulted in lower hepatic VA stores and higher hepatic betaC stores compared with all other groups, suggesting less conversion of betaC to VA. In contrast, consumption of oat gum resulted in hepatic VA and betaC stores that were higher (P = 0.012) and lower (P = 0.022), respectively, than those of citrus pectin-fed gerbils. The level of dietary fat consumed with soluble fiber had no interactive effects on hepatic VA, betaC or alphaC stores. Results demonstrate that betaC BV is independently affected by dietary fat level and type of soluble fiber, and suggest that these dietary components modulate postabsorptive conversion of betaC to VA. This study confirms the negative effects of citrus pectin on betaC BV, and suggests that oat gum does not adversely affect betaC BV.

Primary isolated chylopericardium is a rare disorder in which chylous fluid accumulates in the pericardial space. In this case report of a 61-year-old man with chylopericardium, pedal (99m)Tc-sulfur colloid (SC) lymphoscintigraphy was performed after emergent pericardiocentesis, and when there was a recurrent massive pericardial effusion. The results showed that (99m)Tc-SC lymphoscintigraphy can clearly reveal the lymphodynamics in patients with primary isolated chylopericardium. This noninvasive investigation is valuable and can be easily performed either before or after pericardiocentesis.

It is not clear to what extent methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia effect the severity and extent of coronary atherosclerosis in Asian populations. We examined the MTHFR genotypes and plasma homocysteine (HCY) concentrations in 192 Taiwanese and investigated their relationship with coronary artery disease (CAD), and the severity and extent of coronary atherosclerosis. The distribution of MTHFR genotypes was similar in 116 CAD patients and 76 non-CAD subjects. Homozygosity was noted in 8% of CAD patients and 13% of non-CAD subjects (P=0.33; 95% CI, 0. 2-1.6). The geometric mean of HCY values was higher in CAD patients (11.10+/-1.51 micromol/l) than in non-CAD subjects (9.21+/-1.55 micromol/l) (P=0.003). HCY levels were higher in patients with multi-vessel disease (P<0.05) or in patients with > or = 90% stenotic lesions (P=0.005), compared with non-CAD subjects. The CAD risks in the top two HCY quartiles (> or = 14.0 and 10.1-13.9 micromol/l) were 4.0 (95% CI, 1.7-9.2) and 3.2 (95% CI, 1.4-7.4) times higher than in the lowest quartile (< or = 7.9 micromol/l) (P=0.001 and 0.007, respectively). Linear regression analysis showed significant correlations between HCY concentrations and the severity and extent of atherosclerosis (P=0.0001 for both). In conclusion, hyperhomocysteinemia appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings do not support the homozygous genotype of MTHFR as a genetic risk factor for CAD in this Taiwanese population. Perhaps a further study including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD.

Foods containing provitamin A carotenoids are the primary source of vitamin A in many countries, despite the poor bioavailability of carotenoids. In addition, epidemiologic studies suggest that dietary intake of carotenoids influences the risk for certain types of cancer, cardiovascular disease and other chronic diseases. Although it would be ideal to use humans directly to answer critical questions regarding carotenoid absorption, metabolism and effects on disease progression, appropriate animal models offer many advantages. This paper will review recent progress in the development of animal models with which to study this class of nutrients. Each potential model has strengths and weaknesses. Like humans, gerbils, ferrets and preruminant calves all absorb beta-carotene (betaC) intact, but only gerbils and calves convert betaC to vitamin A with efficiency similar to that of humans. Mice and rats efficiently convert betaC to vitamin A but absorb carotenoids intact only when they are provided in the diet at supraphysiologic levels. Mice, rats and ferrets can be used to study cancer, whereas primates and gerbils are probably more appropriate for studies on biomarkers of heart disease. No one animal model completely mimics human absorption and metabolism of carotenoids; thus the best model must be chosen with consideration of the specific application being studied, characteristics of the model, and the available funding and facilities.

Large-scale clinical trials have shown that long-term treatment with lipid-lowering therapy results in a significant reduction in the occurrence of heart failure among patients with coronary artery disease without previous evidence of congestive heart failure, suggesting dyslipidemia may have an adverse effect on left ventricular performance. To examine whether dyslipidemia has a detrimental effect on left ventricular systolic function and whether this effect is dependent on the corresponding severity of coronary atherosclerosis, 114 consecutive patients with stable angina and a positive exercise thallium-201 myocardial perfusion single-photon emission computed tomography were studied. All patients underwent measurement of serum lipid profiles, right-sided heart catheterization, left ventriculography, and selective coronary arteriography. Mean serum levels of total cholesterol and triglycerides were 4.5 and 1.4 mmol/l, respectively. In univariate analysis, a significant positive correlation between serum high-density lipoprotein (HDL) cholesterol and left ventricular ejection fraction (LVEF) (r = 0.49, P<0.0001) was found. Patients in the lower tertile of serum HDL cholesterol had a significantly lower mean LVEF than those in the upper tertile (55.9+/-15.2 vs. 72.8+/-6.8%, P<0.0001). Stepwise multiple linear regression analysis revealed that LVEF significantly correlated with HDL cholesterol (P<0.0001), the Gensini score (P = 0.008), and diabetes mellitus (P = 0.08) (r = 0.55, P<0.0001). In subgroup analysis of patients with angiographically normal coronary arteries, serum HDL cholesterol was still significantly associated with LVEF. The present study demonstrated an independent association between low HDL cholesterol and subclinical left ventricular systolic dysfunction in Chinese patients with stable angina whose serum levels of total cholesterol and triglycerides were relatively low. Moreover, this correlation remained significant even in patients with normal coronary angiograms, suggesting HDL cholesterol might influence left ventricular systolic performance through extra-atherosclerotic mechanisms.

Objective: To identify coexisting ocular diagnoses in a case series of eyes that developed cystoid macular edema (CME) associated with latanoprost therapy., Design: Retrospective observational case series., Participants: Seven eyes of seven patients who developed CME possibly associated with latanoprost treatment were studied., Intervention: When these patients, all of whom were treated with latanoprost in addition to other glaucoma medications, described blurred vision or eye irritation, ocular examination revealed CME, which was confirmed by fluorescein angiography. Latanoprost was discontinued, and in three cases topical corticosteroids and nonsteroidal anti-inflammatory agents were used to treat the CME., Main Outcome Measures: Visual acuity and intraocular pressure were determined before latanoprost use began, during therapy, and after latanoprost use ceased. In these cases, resolution of CME was documented clinically after discontinuing latanoprost., Results: Clinically significant CME developed after 1 to 11 months of latanoprost treatment, with an average decrease of 3 lines in Snellen visual acuity. Intraocular pressure decreased an average of 27.9% during treatment. Cystoid macular edema was confirmed in all cases by fluorescein angiography. In these seven patients, the following coexisting ocular conditions may have placed these eyes at risk for prostaglandin-mediated blood-retinal barrier vascular insufficiency: history of dipivefrin-associated CME, epiretinal membrane, complicated cataract surgery, history of macular edema associated with branch retinal vein occlusion, history of anterior uveitis, and diabetes mellitus. In all cases, the macular edema resolved following discontinuation of latanoprost, in some instances with concomitant use of steroidal and nonsteroidal anti-inflammatory agents., Conclusions: In this case series of pseudophakic, aphakic, or phakic eyes, the temporal relationships between the use of latanoprost and developing CME, and the resolution of CME following cessation of the drug, suggest an association between latanoprost and CME. In all cases, coexisting ocular conditions associated with an altered blood-retinal barrier were present.

The algae Dunaliella bardawil and Dunaliella salina naturally contain large concentrations of all-trans and 9-cis beta-carotene (betaC). The purpose of this study was to compare the relative serum and tissue accumulation of all-trans and 9-cis betaC in ferrets fed different ratios of all-trans/9-cis betaC derived from two commercial sources, D. bardawil or D. salina (Betatene). Male ferrets (7 wk old) were fed carotene-free, pelleted diets for 27 d. Beginning on d 18, groups of ferrets (n = 6 or 7) received daily, one of six oral supplements varying in ratios of 9-cis and all-trans betaC mixed with approximately 1.0mL of Ensure. Four supplements containing 5.2-8.3 micromol total betaC were prepared from a 20% Betatene preparation, D. bardawil, a high-cis Betatene preparation, and Betatene further enriched in 9-cis betaC with all-trans betaC/9-cis betaC ratios of 2.2, 1.5, 0.6 and 0.4, respectively. Two control supplements, high and low betaC, were prepared from commercial betaC beadlets. The high control supplement had an all-trans/9-cis ratio of 19.0, whereas 9-cis betaC was not detected in the low supplement. On d 27, serum and tissues were obtained for HPLC analysis of betaC and its isomers. Analysis of livers showed that all-trans betaC was the primary isomer present, but 9-cis and other isomers were also detected in all groups. The hepatic all-trans/9-cis ratios were 5.9, 4.9, 2.5, 1.4, 52.2 and47.5, respectively, for the groups listed above. Lower amounts of all-trans and 9-cis betaC were found in kidneys compared with the liver, but ratios of all-trans/9-cis were not different among groups. Only trace amounts of 9-cis betaC were found in serum. These results demonstrate that the algae D. bardawil and D. salina provide a bioavailable source of betaC isomers, but, as in humans, absorption of 9-cis betaC is poor and any 9-cis betaC absorbed is apparently cleared by the liver.

Vitamin A (VA) deficiency remains a serious problem in the world today. Current approaches to preventing or treating VA deficiency, including dietary intervention with provitamin A compounds, rely on the body converting ingested beta-carotene (betaC) to VA. However, it is not known whether betaC that is already in the tissues can be used as a source of VA to prevent deficiency. The objectives of these studies were to determine whether tissue betaC stores are converted to VA when the Mongolian gerbils have low VA status and whether previously fed betaC is retained in the tissues for later conversion to VA. In the first study, gerbils were prefed diets with betaC (20.3 +/- 6.2 nmol/g diet) (+betaC) or without betaC (-betaC), and with VA [2.4 +/- 1.5 nmol/g diet (+betaC diet) or 12.0 +/- 4.2 nmol/g diet (-betaC diet)] for 7 d, and then depleted of both betaC and VA for up to 84 d. On d 0 after the prefeeding period, hepatic betaC stores were 13.3 +/- 9.1 nmol. These stores were significantly lower after 28d of consuming the -VA/-betaC diet (2.16 +/- 1.7 nmol), even though the hepatic VA concentrations did not change. In the second study, the gerbils were prefed a -VA/+betaC diet (74.3 +/- 19. 7 nmol betaC/g diet) for 7 d, and then fed a betaC-free diet either with (7.1 +/- 1.4 nmol/g) or without VA for up to 34 d. Hepatic betaC stores after the 7-d prefeeding period were 38.1 +/- 20.6 nmol, and were significantly higher than after 7d of consuming either a +VA/-betaC (12.4 +/- 10.8 mmol) or -VA/-betaC diet (11.4 +/- 8.0 nmol). The results from both studies suggest that a substantial amount of hepatic betaC is rapidly lost when betaC is eliminated from the diet and therefore is not conserved to meet later VA needs. The presence of VA in the diet (Study 2) did not affect the rate of betaC loss from the serum and tissues. Moreover, no evidence was found that the stored betaC was utilized for VA. The data suggest that there may be two pools of hepatic betaC, one that is lost rapidly and another that is lost more slowly over time, but losses are not affected by VA status.

Vitamin A (VA) deficiency is the leading cause of blindness in children in developing countries. Dietary intervention with foods rich in provitamin A carotenoids, such as beta-carotene (betaC), has been suggested as one solution to this problem. The objective of the two studies described in this paper was to examine the utilization of betaC as a source of VA at different stages of VA depletion using the Mongolian gerbil as a model. Male 4- to 5-wk-old Mongolian gerbils were fed powdered betaC-free semipurified diets either with or without VA for 26 d (Study 1), or without VA for 8-10 wk (Study 2). Gerbils were then fed diets with or without VA (20.9 nmol/g diet) and/or betaC [(67.0 micromol/g diet (Study 1) and 145.9 micromol/g diet (Study 2)] for variable periods. Two (Study 1) or three (Study 2) days before termination of the study, 3-4 gerbils per group were dosed orally with 14C-betaC. Tissues were evaluated for VA and betaC content by HPLC. Liver was extracted with and without saponification to evaluate 14C-betaC and 14C-VA content. The results demonstrate the following: 1) the gerbil is an appropriate animal model to study betaC utilization; 2) 20.9 nmol VA/g diet is more than sufficient for this species; 3) the daily VA utilization rate for this species is calculated to be 3.1 microg/100 g body weight; 4) a highly bioavailable source of betaC at a 6:1 weight ratio of betaC:VA is sufficient to reverse marginal VA status in this model; and 5) a highly bioavailable source of betaC fed between a 6:1 and 13:1 weight ratio to VA provides equivalent VA status as preformed VA in Mongolian gerbils.

The effects of zinc deficiency on hepatic cell mitotic and peritoneal macrophage phagocytic activities were examined in mice infected with Trypanosoma musculi or immunized with parasitic products. On a full-complement or pair-fed diet, infected and homogenate-inoculated mice showed mitotic activity gains of 7.9% to 80.3% and 6.5% to 99.0%, respectively. Infected and homogenate-inoculated mice on a zinc-deficient diet showed 21.8% to 95.7% and 17.2% to 65.2%, respectively, more dividing liver cells compared with controls. In comparison to controls, macrophages isolated from infected and homogenate-immunized mice on full-complement or pair-fed diets had phagocytized 13.4% to 31.4% more latex particles from day 50 to 80. In the zinc-deficient group, macrophages isolated from infected mice had significant numbers of phagocytized latex particles (1.8% to 38.5%) from day 20 to day 80 compared with controls. The homogenate-immunized mice also had increased numbers (18.6 to 30.8%) of phagocytized latex particles.

We present a case of giant superior mesenteric artery (SMA) aneurysm in a patient with systemic lupus erythematosus (SLE). The ultrasound, computed tomography, magnetic resonance, and angiographic findings are discussed. To our knowledge, SLE associated with a giant SMA aneurysm as a late complication of previous lupus mesenteric arteritis has not been reported previously.

This study examined the effect of zinc deficiency on food consumption and the growth of mice infected with Trypanosoma musculi or immunized with parasite products. In addition, the effects of zinc deficiency on the growth and development of parasites in vivo was studied. Infected mice consumed more food than noninfected mice, and the level of food consumption in the zinc-deficient mice was much less and showed general decline during the observation period. Also, infected mice on both full-complement and zinc-deficient diets gained more body weight than control mice. Throughout the observational period, trypanosomes from zinc-deficient mice showed considerably higher variability in size as determined by coefficient of variation. In both dietary groups, the average length of trypanosomes was not significantly different.

Maternal riboflavin-binding protein (RfBP) mediates the deposition of riboflavin in avian eggs. A strain of Single-Comb White Leghorn chicken, genetically unable to synthesize RfBP, produces eggs deficient in riboflavin. Embryos in these eggs die on or about 13 of incubation, with severe hypoglycemia and impaired fatty acid oxidation. Injection of free riboflavin prior to incubation allows these embryos to survive and hatch normally. The egg whites of eggs from the RfBP-deficient strain were injected with different relative amounts of riboflavin and RfBP to determine their effects on the developing embryo. Injection of protein-bound riboflavin resulted in a substantial number of the embryos (27%) surviving until the end of the experiment (d 19) with an average weight of 13.7 g, demonstrating that some embryos were able to use the bound riboflavin. In control groups injected with riboflavin alone, 10 of 17 embryos survived until d 19 with an average weight 18.5 g, whereas those injected with saline died between d 10 and 13 with an average weight of 3.8 g. A fourth group, injected with apo-RfBP, produced embryos with an average weight of 0.24 g. This early death suggests that the protein scavenges the small amount of riboflavin normally available to the early embryo. Further studies showed that titration of RfBP-binding sites with exogenous riboflavin lessens this effect. These studies show that although riboflavin-binding protein is essential for the deposition of riboflavin in eggs, its presence in excess can diminish the availability of riboflavin to the chicken embryo.

A nephritic condition was developed by infecting Swiss Webster albino mice with the malarial parasite Plasmodium berghei NK 65. These animals were tested for urinary protein and the presence of circulating immune complexes using reagent strips and a polyethylene glycol (PEG) precipitation assay. The circulating immune complexes were isolated from the sera using both affinity chromatography and PEG precipitation and from the kidney by acid elution. The isolated complexes were dissociated into their individual components and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The components of the complexes were transferred to nitrocellulose sheets and probed for the presence of malarial antigens using a rabbit anti-P berghei antisera. The overall humoral response to the malarial parasite was evaluated using a radial immunodiffusion assay. The present study confirmed that the malarial-infected animals not only developed the nephritic condition (as evident by the high levels of proteinuria) but also, as indicated by the PEG assay, have the presence of high levels of circulating immune complexes in their serum. The apparent absence in the SDS gels of any abnormal protein bands followed by the inability of the Western blot to reveal any malarial antigens provides some of the strongest evidence to date that these malarial proteins are not directly involved in the circulating immune complexes believed to be responsible for producing this nephritic condition.

Objective: An abnormal umbilical artery Doppler waveform is a risk factor for adverse perinatal outcome. However, it has not been established whether this is related to the earlier gestational age at delivery of fetuses with abnormal Doppler findings or whether Doppler findings are an independent predictor of perinatal outcome. Our purpose was to determine whether an abnormal Doppler umbilical artery waveform is associated with adverse perinatal outcome even after the gestational age at delivery is controlled for as a confounding variable in patients with preeclampsia., Study Design: Umbilical artery velocimetry studies were performed within 7 days of delivery in 72 consecutive patients admitted to our unit with preeclampsia. Adverse perinatal outcome was defined as fetal distress requiring cesarean delivery. Apgar score < 7 at 5 minutes, significant neonatal morbidity, or perinatal death. Significant neonatal morbidity was defined as neonatal sepsis, intraventricular hemorrhage (grade > or = 2), respiratory distress syndrome, pneumonia, bronchopulmonary dysplasia, acute renal failure, or necrotizing enterocolitis. Stepwise multiple logistic regression and receiver-operator characteristic curve analysis were used., Results: Patients with abnormal umbilical artery velocimetry had a significantly higher rate of complications, including cesarean section for fetal distress, preterm delivery, low Apgar scores, significant neonatal morbidity, and perinatal death, than did patients with a normal waveform. Receiver-operator characteristic curve and stepwise logistic regression analysis indicated that an abnormal umbilical artery waveform was a significant independent predictor for the development of adverse perinatal outcome (odds ratio 14.2, p < 0.005) after other confounding variables were adjusted., Conclusion: An abnormal Doppler umbilical artery waveform is a strong and independent predictor of adverse perinatal outcome in patients with preeclampsia.

A metabolic imbalance technique was used to study the effects of zinc deficiency on immunoglobulin levels in mice infected with Trypanosoma musculi or immunized with parasite products. Zinc-deficient mice developed higher numbers of parasitemia earlier and exhibited prolonged infection. Irrespective of the diet, higher IgG1, IgG2b, and IgM levels, lower IgG2a and IgA levels, and uniform IgG3 levels were exhibited primarily by mice infected with T musculi and to a lesser extent by mice immunized with parasite products. Zinc-deficient mice showed smaller increases in IgG1 and IgM, but larger gains in IgG2b compared with mice on full-complement and pair-fed diets. However, IgG2a decreased significantly in zinc-deficient mice.

Lithospermic acid B has been isolated to > 95% purity by high performance liquid chromatography from the aqueous extract of the roots of Salvia miltiorrhiza. When infused at 5.5 mumoles/kg into the post-ischemic rabbit heart, it reduced by 62 +/- 10% (n = 8) the myocardial damage found in the saline control in a rabbit ischemia-reperfusion model.

Lithospermic acid B, an active principle found in a Chinese herbal medicine for treating various heart ailments, was recently isolated, purified and demonstrated by us to salvage the postischemic rabbit heart from reperfusion injury. In this work, we further report that lithospermate B is able to protect each of two types of rabbit cardiocytes, namely ventricular myocytes and aortic endothelial cells against necrosis inflicted by oxyradicals generated pharmacologically with xanthine oxidase and hypoxanthine. Biochemically, the lithospermate B also inhibits the reduction of cytochrome c by superoxide radical anion. Thus, our in vitro data here are in concord with our earlier in vivo finding that lithospermic acid B is most likely an effective antioxidant-based myocardial protector.

Background: Subfoveal choroidal neovascularization (CNV) usually is associated with a poor visual prognosis. Laser photocoagulation of certain subfoveal membranes secondary to age-related macular degeneration (ARMD) appears preferable to observation based on recent Macular Photocoagulation Study (MPS) findings but is associated with decreased vision. The authors explored the use of vitreoretinal surgical techniques as an alternative method of eradicating subfoveal CNV., Methods: After vitrectomy, a small retinotomy technique was used to extract or disconnect from the choroidal circulation subfoveal CNV in 58 eyes. There were 33 eyes with ARMD, 20 eyes with presumed ocular histoplasmosis, and 5 eyes with miscellaneous etiologies. Five eyes also received subfoveal RPE patches., Results: With limited follow-up, significant improvement in vision (defined as 2 Snellen lines) was achieved in 7 of 22 eyes with ARMD CNV removal (1 eye 20/20), 0 of 4 eyes with ARMD CNV removal and RPE patches, and 1 of 7 eyes with ARMD CNV disconnection. Significant improvement was achieved in 6 of 16 eyes with presumed ocular histoplasmosis removal and 0 of 4 eyes with presumed ocular histoplasmosis CNV disconnection. In 5 eyes with miscellaneous CNV, 2 improved (20/20 and 20/40). CNV recurred in 29%., Conclusions: Some patients with subfoveal CNV appear to benefit from surgical removal. Only rarely do eyes with ARMD improve. Longer-term follow-up and refined case selection are required before this approach can be widely recommended.

The authors reviewed the records of 302 eyes of 185 patients with diffuse diabetic macular edema with or without cystoid macular edema treated with modified grid laser photocoagulation between the years 1981 and 1990. Three years after initial grid treatment, visual acuity was improved in 14.5%, unchanged in 60.9%, and worse in 24.6% of eyes. The average number of treatments per eye was 1.9. These results show that in assessing long-term visual outcome, modified grid laser photocoagulation is an effective modality in maintaining or improving visual acuity in eyes with diffuse diabetic macular edema. The effectiveness demonstrated in this study is without comparison with control subjects with no treatment or comparison with other treatment techniques.

Histochemical variations in tissues from rats inoculated with Trypanosoma lewisi and Trypanosoma rhodesiense were investigated. During peak parasitemia, the liver of rats inoculated with T lewisi showed increased glycogen distribution. However, glycogen depletion was noted in the liver and spleen of animals inoculated with living cells of T rhodesiense. Depletion was very apparent from day 4 to day 10. Throughout the period of observation, only a small amount of lipid infiltration occurred in tissues from animals inoculated with both organisms. Protein tests revealed a normal distribution of protein in tissues. Sections of the liver from rats inoculated with T lewisi showed strong alkaline phosphatase activity on days 7, 10, and 13. Alkaline phosphatase activity for T rhodesiense-infected animals was positive for days 4, 7, and 10. Strong positive reactions for acid phosphatase were observed on days 10 and 13 for some tissues (liver, spleen, and kidney) from rats inoculated with T lewisi. On days 4, 7, and 10, intense staining reactions also were observed for livers and spleens of animals inoculated with T rhodesiense. Regardless of tissues observed, histochemical variations were not observed in animals inoculated with the derivatives (ie, metabolic products and homogenates) of T lewisi and T rhodesiense.

HDV-RNA displays genetic heterogeneity at several different levels. This heterogeneity is likely reflected in the biological properties, such as pathogenicity and evolution, of HDV. The variation and progression of the clinical picture of delta hepatitis is likely associated with the heterogeneity of the virus. The mechanism of the generation of the heterogeneity remains largely to be studied.

Selective C-8 modifications of 2,6-anhydro-3-deoxy-D-glycero-D-talo-octonic acid ("2,3-dideoxy-beta-D-manno-2-octulosonic acid", 1a) were effected via the protected 8-hydroxy derivatives 2d and 2e. Swern oxidation of 2d and 2e gave the aldehydes 3a and 3b, respectively. Compounds 3a and 3b were converted into the oxime 13b and the O-methyloxime 13c derivatives, respectively. Methodology was developed for selective cleavage of the protecting groups of 13b and 13c to give the deprotected oxime 12m and the deprotected O-methyloxime 12n, respectively. Side chain-extended products were prepared from the aldehyde 3a utilizing Wittig methodology. The branched chain allylic amine 12p was prepared from 3a in a sequence the keys steps of which were preparation of the methyl ketone 19a using LiCuMe2, followed by Swern oxidation, methylenation of 19a using CH2I2-Zn-TiCl4 to give the alkene 19b, followed by Wohl-Ziegler bromination of 19b to give the allylic bromide 19c, and conversion of the latter to the allylic azide 19d. A number of the analogs showed significant activities vs CMP-Kdo synthetase. The most active of these was the side-chain extended alkene 12d, which proved second in activity only to the 9-amino analog (1c).

Plasma lipid and lipoprotein concentration and high density lipoprotein (HDL) kinetics were determined in control subjects and patients with chronic renal failure (CRF). Results demonstrated that plasma triglyceride (TG) concentration was significantly higher (P less than 0.001) in patients with CRF, associated with a significant increase in plasma VLDL-cholesterol (P less than 0.002) and a significant decrease (P less than 0.05) in plasma HDL-cholesterol concentration. The rate of removal of 125I-apoAI/HDL from plasma was slower (P less than 0.001) in the patients with CRF, resulting in an increase in the residence time of 125I-apoAI/HDL (P less than 0.001) and a decrease in the fractional catabolic rate (P less than 0.001). Since plasma apoAI concentration was lower in patients with CRF, total apoAI/HDL synthetic rate was also significantly (P less than 0.05) decreased. These data provide support for the view that low plasma HDL-cholesterol concentrations in patients with CRF are related to decreases in the synthetic rate of apoAI/HDL.

A metabolic imbalance technique was employed to study vitamin B(12) deficiency in rats infected with Trypanosoma lewisi. Throughout the observational period, animals on the deficient diet had lowered serum vitamin B(12) levels compared with complete and pair-fed animals. The decline in the level of the vitamin, ten days after the initiation of the experiment, continued progressively until the termination of the study. Body weight gains and food consumption in rats on complete, vitamin B(12)-deficient, or pair-fed diets and inoculated with T lewisi showed significant increase over inoculated controls. The rates of body weight and food consumption in vitamin B(12)-deficient animals were significantly less than that of the adequately fed animals.The indices of lowered resistance to infection in the vitamin B(12)-deficient rats were manifoid. Deficient rats suffered earlier and higher parasitemia followed by persistent infection. The delay in the synthesis of the reproductive inhibiting antibody (ablastin) resulted in prolonged variability in the length of the trypomastigotes. Severe depression in the primary and secondary antibody responses (IgG and IgM) to in vivo immunization of sheep erythrocytes was also observed in the deficient animals. In comparison, the level of IgG antibody decreased approximately one fifth the control values.

Rats infected with Trichinella spiralis were examined during the course of infection for various changes in the leucocytic population. In each experiment rats were divided into three groups: Group A, inoculated with Escherichia coli B-5-lipopolysaccharide (LPS) administered four days before each experiment; Group B, infected with Trichinella spiralis; and Group C, untreated controls.An extensive leucocytosis was observed in the peripheral blood and peritoneal cavity of infected rats. Regardless of the site (peripheral blood, bone marrow, peritoneal cavity), the most obvious change was an increase in eosinophils. Differential counts of peritoneal exudate cells also revealed a significant population of macrophages. Acid phosphatase activity, macrophage phagocytosis of polystyrene latex particles, and macrophage spreading revealed that peritoneal exudate cells from T spiralis-infected rats are activated from 6 to 48 days postinfection.This paper serves to reinforce existing information on the changes and state of the various leucocytic populations during infection with T spiralis and aids in assessing the activity change of macrophages.

Trichinosis is world-wide in distribution, occurring in tropical, temperate, and polar regions. Although incidence of the disease appears to be declining in most regions, it is still widely distributed in Europe and is increasing in many parts of Africa. In recent years, the incidence of trichinosis in the United States also has increased. This article reviews the nature of immunity to trichinosis.

The influence of trace metal contaminants (lead, cadmium, and mercury) on Sprague-Dawley rats was investigated to determine whether subclinical levels of these metals might have adverse effects on the host's ability to respond to an infective agent.In the present study, a trace metal contaminant-trypanosome system was employed to observe the hematological changes in rats infected with Trypanosoma lewisi. The animal groups were: (1) lead (Pb), (2) cadmium (Cd), (3) mercury (Hg), and (4) controls (animals not exposed to trace metals).Regardless of the trace metals, infected animals showed decreases in total erythrocyte counts and lower hematocrit values. Generally, infected animals also showed increases in total leucocyte counts, decreases in the percentages of lymphocytes and monocytes, increases in percentage of neutrophils, and no changes in percentages of eosinophils and basophils.

Although malaria and hookworm disease appear to be on the decline, another dreaded parasitic disease-schistosomiasis-is on the increase. Presently, the number of infected individuals with schistosomes is estimated to be 250 million, and even though only a small proportion of them become sick and die, schistosomiasis remains a medical problem of great significance. The high incidence of infection of man with Schistosoma mansoni, Schistosoma japonicum or Schistosoma haematobium, as well as the chronic debilitating diseases produced, places these organisms among the world's most important infectious agents. This paper discusses the nature of immunity to schistosomiasis.

On the basis of evidence of the suppressing effect of cocoa on human lactose intolerance, a feeding study was conducted on 35 subjects with a commercial chocolate-milk formula. Variables studied were breath hydrogen level (BHL), symptoms, and onset time. Data from repeated feeding were analyzed by paired t tests. The addition of cocoa significantly reduced BHL (p less than 0.005) as well as the symptom score of both bloating (p less than 0.05) and cramping (p less than 0.025). Individual lactose intolerance levels ranged from 5% (basal milk) to 12.5% with an average of 7.8% upon consumption of 250 mL milk. Having both plain and cocoa formulas contain sucrose and carrageenan led to a conclusion that the suppressive effect of cocoa observed was independent of the presence of sucrose and carrageenan. Ninety-five percent of the subjects responded positively (BHL greater than 17 ppm) to the plain and 51% to the cocoa formula.

The Health Science Institute of Howard University was initiated during the summer of 1973 by students and faculty members in the Colleges of Liberal Arts and Pharmacy and Pharmacal Sciences to address one of the major problems related to the overall poor status of health-care delivery for residents of the nation's underserved areas-the critical health manpower shortage.

Binding of the potent nucleoside transport inhibitor [3H]nitrobenzylthioinosine to rat and guinea pig lung membranes was investigated. Reversible high-affinity binding was found in both species (apparent KD approximately 0.3nM). Binding was inhibited by nitrobenzylthioguanosine, adenosine and uridine. Dipyridamole was also an effective inhibitor of [3H]nitrobenzylthioinosine binding to guinea pig membranes. In contrast, rat membranes were relatively insensitive to dipyridamole. Exposure of site-bound [3H]nitrobenzylthioinosine to high intensity U.V. light resulted in the photoaffinity labelling of lung proteins with apparent molecular weights similar to that of the human erythrocyte nucleoside transporter (45,000-65,000).

Oxygen consumption of Trypanosoma lewisi grown in albino and black rats was measured by the direct method of Warburg. Respiration rates in buffered Ringer's solution, with and without glucose and in normal serum from the respective hosts, were determined for T lewisi grown in albino and black rats. Significantly higher respiratory rates were obtained for trypanosomes grown in albino hosts: 31 percent higher in buffered Ringer's solution with glucose and 26 percent higher in homologous serum.In this study, in which the development of the parasitemia was observed for 27 days, T lewisi populations were higher in albino rats than in black rats.

The responses of adult women to two levels of vitamin B6, was conducted with five young and eight middle-aged subjects. A constant diet (2.3-2.4 mg vitamin B6 per day) was fed for four weeks followed by three weeks of the same diet supplemented with 8.0 mg pyridoxine. Plasma pyridoxal 5'-phosphate (PLP), plasma and urinary vitamin B6, and urinary 4-pyridoxic acid (4-PA) were determined. The older women had significantly lower plasma PLP, plasma and urinary vitamin B6 and slightly higher urinary 4-PA values on normal vitamin B6 intakes. With supplementation, only the difference in urinary total vitamin B6 remained significant. Tryptophan load tests revealed no significant between-group differences in xanthurenic acid or kynurenic acid excretion. These results demonstrate an age-related difference in vitamin B6 status indicators in women under controlled dietary intake of vitamin B6.

Malnutrition combined with susceptibility to infection threatens the health and survival of a large portion of the world's population. Of the many components of the host-parasite relation, nutrition has not received the attention it deserves. There has been increasing activity in recent years on the elucidation of the role nutritional factors play in the behavior of both host and parasite.This paper reviews the effects vitamins exert on the course of parasitic infections.