Topical adjuvants incompletely remove adherent Staphylococcus aureus from implant materials

Adjuvant treatments including Betadine, Dakin's solution (sodium hypochlorite), or hydrogen peroxide (H₂O₂) have been attempted to eradicate prosthetic joint infection caused by biofilm or intracellular bacteria. The purpose of this study was to evaluate the in vitro abilities of chemical adjuvants to decrease Staphylococcus aureus (S. aureus) biofilm presence on orthopaedic implant grade materials, including titanium, stainless steel, and cobalt chrome. S. aureus biofilms were grown for 48 h and evaluated for baseline colony forming units/centimeter squared (CFU/cm²) and compared to treatments with Betadine, Dakin's solution, H₂O₂, or 1% chlorine dioxide (ClO₂). Control discs (n = 18) across all metals had an average of 4.2 × 10⁷ CFU/cm². All treatments had statistically significant reductions in CFU/cm² when compared to respective control discs (p < 0.05). For all metals combined, the most efficacious treatments were Betadine and H₂O₂, with an average 98% and 97% CFU/cm² reduction, respectively. There were no significant differences between reductions seen with Betadine and H₂O₂, but both groups had statistically greater reductions than Dakin's solution and ClO₂. There was no change in antibiotic resistance patterns after treatment. Analysis of S. aureus biofilms demonstrated a statistically significant reduction in biofilm after a five‐minute treatment with the modalities, with an average two log reduction in CFU/cm². Statement of clinical significance: While statistically significant reductions in CFU/cm² were accomplished with chemical adjuvant treatments, the overall concentration of bacteria never fell below 10⁵ CFU/cm², leading to questionable clinical significance. Further techniques to eradicate biofilm should be investigated. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1599–1604, 2018.

     

Comparison of HCV-associated gene expression and cell signaling pathways in cells with or without HCV replicon and in replicon-cured cells

Background

Hepatitis C virus (HCV) replication is affected by several host factors. Here, we screened host genes and molecular pathways that are involved in HCV replication by comprehensive analyses using two genotypes of HCV replicon-expressing cells, their cured cells and naïve Huh7 cells.

Methods

Huh7 cell lines that stably expressed HCV genotype 1b or 2a replicon were used. The cured cells were established by treating HCV replicon cells with interferon-alpha. Expression of 54,675 cellular genes was analyzed by GeneChip DNA microarray. The data were analyzed by using the KEGG Pathway database.

Results

Hierarchical clustering analysis showed that the gene-expression profiles of each cell group constituted clear clusters of naïve, HCV replicon-expressed, and cured cell lines. The pathway process analysis between the replicon-expressing and the cured cell lines identified significantly altered pathways, including MAPK, steroid biosynthesis and TGF-beta signaling pathways, suggesting that these pathways were affected directly by HCV replication. Comparison of cured and naïve Huh7 cells identified pathways, including steroid biosynthesis and sphingolipid metabolism, suggesting that these pathways were required for efficient HCV replication. Cytoplasmic lipid droplets were obviously increased in replicon-expressing and cured cells as compared to naïve cells. HCV replication was significantly suppressed by peroxisome proliferator-activated receptor (PPAR)-alpha agonists but augmented by PPAR-gamma agonists.

Conclusion

Comprehensive gene expression and pathway analyses show that lipid biosynthesis pathways are crucial to support proficient virus replication. These metabolic pathways could constitute novel antiviral targets against HCV.     

Pharmacokinetics of ivermectin applied topically by whole‐body bathing method in healthy volunteers

As a novel administration method of ivermectin (IVM) for scabies treatment, we proposed a “whole‐body bathing method (WBBM)”. In this method, the patients would bathe themselves in a bathing fluid containing IVM at an effective concentration. Previously, we demonstrated that WBBM could deliver IVM to the skin but not to the plasma in rats. In the present study, to assess the clinical validity of the method an arm bathing examination (first trial) and a whole‐body bathing examination (second trial) were conducted in healthy volunteers. In both the first and second trials, after bathing in fluid containing IVM, the exposure in the stratum corneum was higher compared with that after taking IVM p.o. as reported previously. IVM was not detected in plasma at any sampling point after the whole‐body bathing in the second trial. Furthermore no serious adverse events were found. These results in both trials suggest that WBBM can deliver IVM to the human stratum corneum without systemic exposure or serious adverse effects in healthy volunteers, and at concentrations that would be adequate for scabies treatment.     

Identification of a compound heterozygous inactivating ABCC8 gene mutation responsible for young‐onset diabetes with exome sequencing

Activating mutations in the ABCC8 gene cause diabetes and inactivating mutations usually cause hyperinsulinemic hypoglycemia in infancy. Patients with hypoglycemia in infancy due to a heterozygous inactivating mutation have been reported to occasionally progress to diabetes later in life. We explored the gene responsible for diabetes in two brothers, who were suspected to have diabetes at 15 and 18 years‐of‐age, respectively, with whole exome sequencing, and identified a compound heterozygous ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). Although their father and mother were heterozygous carriers of the p.Arg168Cys and the p.Arg1421Cys mutation, respectively, neither parent had diabetes. These mutations have been reported to be responsible for hypoglycemia in infancy and function as an inactivating mutation. Our results suggest that the inactivating ABCC8 gene mutation is also important in the etiology of diabetes.     

Safety and efficacy of radiofrequency thermal ablation in advanced liver tumors

HYPOTHESIS: Radiofrequency thermal ablation (RFA) can be performed safely and effectively to control local disease in patients with advanced, unresectable liver tumors. DESIGN, SETTING, AND PATIENTS: Prospective study of 76 patients with unresectable liver tumors who underwent RFA at a private tertiary referral hospital. INTERVENTIONS: Ninety-nine RFA operations were performed to ablate 328 tumors. MAIN OUTCOME MEASURES: Complications and local recurrence. RESULTS: There was 1 death (1%), major complications occurred in 7 operations (7%), and minor complications occurred in 10 operations (10%). Local recurrence was identified in 30 tumors (9%) at a mean follow-up of 15 months. Size (P<.001), vascular invasion (P<.001), and total volume ablated (P<.001) were associated with recurrence but the number of tumors was not (P =.39). CONCLUSION: Radiofrequency thermal ablation provides local control of advanced liver tumors with low recurrence and acceptable morbidity.     

Effect of subarachnoid hemorrhage on serotonin uptake and release in the rabbit basilar artery

This study analyzes the changes induced by subarachnoid hemorrhage (SAH) on the serotonin (5-hydroxytryptamine, 5-HT) uptake and release evoked in rabbit basilar arteries by tyramine. Rabbits were injected with 5 ml of autologous arterial blood into the cisterna magna to produce SAH. Tritium accumulation in basilar arteries was measured after 30 minutes of incubation with 10(-7) M [3H]5-HT and a subsequent 120-minute superfusion (1 ml/min) period. The uptake of 5-HT by arteries 1, 2, 3, and 7 days after SAH was found to be 109%, 69%, 57% (P less than 0.05), and 67% (P less than 0.05) (n = 4, 4, 9, and 6; P less than 0.05) of control (n = 13; 16.8 +/- 1.2 X 10(2) dpm/mg tissue), respectively. The neuronal (cocaine-sensitive) uptake of 5-HT in the arteries 3 days after SAH decreased to approximately 38% of control, whereas the extraneuronal (cocaine-insensitive) uptake of both groups had almost the same absolute value (n = 6 and 6; 4.4 +/- 0.4 and 4.8 +/- 0.4 X 10(2) dpm/mg). Autoradiographic study disclosed that dense clusters of silver grains in the adventitia were not observed after treatment with cocaine (3 X 10(-5) M), although a diffuse distribution of grains was present throughout the vascular wall. The labeled arteries were stimulated by superfusion of tyramine, which is known to replace amines in the sympathetic nerve ending. Tyramine (10(-6) and 10(-4) M)-induced 3H efflux was significantly potentiated by SAH (n = 6) and was suppressed by treatment with cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relative efficacy of terazosin versus terazosin and flutamide for the treatment of symptomatic BPH.

Pharmacotherapy for the treatment of BPH is currently being targeted to relax prostate smooth muscle (alpha blockade) and decrease prostate volume (androgen suppression). The objective of the present study was to determine the relative efficacy of terazosin vs. terazosin and flutamide (combination therapy) for the treatment of symptomatic BPH. Twenty-nine males with symptomatic BPH were enrolled into this 6-month open label study. The entry criteria included peak urinary flow rate between 4-15 ml/sec, a total Boyarsky symptom score greater than 7, and postvoid residual less than 300 ml. The daily dosage of terazosin was titrated to 5 mg over a 2-week interval. A 750 mg daily dosage of flutamide was added following 1 month of terazosin monotherapy. The dosages were lowered if significant adverse events developed. Efficacy assessments were performed at 1 month (terazosin alone), 6 months (combination therapy), or at the time of early withdrawal from the study. The efficacy of combination therapy was evaluable in 24 patients receiving combination therapy. At one month, the mean peak urinary flow rate and mean total Boyarsky symptom score improved 38% and 56% relative to baseline, respectively. The present study confirmed the previously observed efficacy and safety of terazosin for BPH. The addition of flutamide did not result in statistically significant improvements in the peak urinary flow rate or total Boyarsky symptom score. The adverse events related to flutamide resulted in 16 dose reductions and 14 premature withdrawals. The role of combination therapy will require a randomized placebo controlled study sufficiently powerful to identify clinically and statistically significant improvements in objective outcome parameters relative to the monotherapies.     

Relationship between dietary folate intakes,maternal plasma total homocysteine and B-vitamins during pregnancy and fetal growth in Japan

Background Adequate folate status in pregnancy is important for satisfactory pregnancy outcome. Aim of the Study The objective of the present study was to evaluate folate status in healthy pregnant women by assessing dietary folate intakes and measuring changes in folate-related biomarkers including plasma tHcy, serum vitamin B₁₂ (B₁₂), and serum and RBC folate concentrations in each trimester and to examine their relation to fetal growth. Methods From 94 pregnant women, 3-day-dietary records were obtained and blood was collected for plasma total homocysteine (tHcy), serum B₁₂, and serum and red-blood cell (RBC) folate measurements. Infant anthropometric measurements were made immediately after birth. Results Average folate intake was less than 300 μg/day with a mean energy intake of about 1800 kcal. Mean serum and RBC folate concentrations declined significantly during gestation (p < 0.05). Mean serum B₁₂ also significantly decreased (p < 0.01), whereas plasma tHcy increased from 5.1 in the first trimester to 5.9 μmol/l in the third trimester (p < 0.01). Multiple regression analyses, after controlling for maternal age, parity and pre-pregnancy body-mass index indicated that a 1.0 μmol/l increase in plasma tHcy in the third trimester corresponded to a 151 g decrease in birth weight (p < 0.01). Neither B₁₂ nor folate concentrations in all three trimesters showed any significant associations with birthweight. Plasma pyridoxal-5′-phosphate concentrations were markedly low, and were consistent with low intake of vitamin B₆ in our population. Conclusion Our data suggest that higher plasma tHcy in the third trimester is a predictor of lower birth weight. In general, the dietary intake of B-vitamins and energy may be inadequate in our population, suggesting intervention is necessary.