Table Table2 Research Articles

Probing the Selectivity of Monoamine Transporter Substrates by Means of Molecular Modeling

Probing the Selectivity of Monoamine Transporter Substrates by Means of Molecular Modeling

Discordant Results of Two Automated Assays for Detection of Hepatitis C Virus-Specific Antibody

Discordant Results of Two Automated Assays for Detection of Hepatitis C Virus-Specific Antibody

Nuclear Translocation Peptides as Antibiotics

Human immunodeficiency virus (HIV) Tat and antimicrobial peptides, such as LL-37, which transfer extraneous DNA to nucleus of host cells are known (5, 6). We performed experiments to find an antimicrobial function for nuclear localization signals (NLS) and nuclear export signals (NES), which are nuclear translocation signals required for shuttling cellular proteins between the nucleus and the cytoplasm (3, 4, 7). Consequently, we obtained evidence that the peptides, which consist of NLS tandems or combinations of NLS and NES, are effective antimicrobial peptides. The antimicrobial activity of these combination peptides for both gram-negative and gram-positive bacteria is very high, and antimicrobial peptides comprised of NLS and NES have the potential to become a new base for peptide antibiotics. The different combinations of NLS and NES within the peptidic design principle comprise eight types of results: the NLS simple sequence, the NLS tandem sequences (NLS+NLS and NLS+NLS+NLS), the NES simple sequence, the NES tandem sequence (NES+NES), the sequence composed of NES linked to an NLS C terminus (NLS+NES), the sequence composed of NLS linked to an NES C terminus (NES+NLS), and the sequence composed of NLS linked to an NLS+NES C terminus (NLS+NES+NLS). The eight types of peptides were synthesized by following the 9-fluorenylmethoxycarbonyl solid-phase synthesis method and purified by reverse-phase high-performance liquid chromatography on a C18 column (purity of ≥95%), and their antimicrobial function against the gram-positive bacterium Staphylococcus aureus IFO12732 and the gram-negative bacterium Escherichia coli IFO12713 was tested using the microbroth dilution method to evaluate their MICs. The results are shown in Table ​Table1.1. The antimicrobial activity for four types of NLS simple sequence (simian virus 40 [SV40] large T antigen, p54, SOX9, and NS5A) was present but weak. However, it was found that antimicrobial function increased remarkably when NLS was made into a tandem sequence (NLS+NLS). More specifically, the antimicrobial performance improved from 30 to 100 times that of NLS on its own. Moreover, the antimicrobial performance results against both gram-positive and gram-negative bacteria further improved several times by making NLS into the three NLS tandem sequence (NLS+NLS+NLS) and the NLS+NES+NLS tandem sequence. Also, NLS-linked NES (NLS+NES, NES+NLS) demonstrated a particularly strong antimicrobial effect against S. aureus. Compared to these results, the NES simple sequence and the NES tandem sequence (NES+NES) did not demonstrate a significant antimicrobial effect. TABLE 1. MICs for combination peptides of NLS and NES To evaluate the peptidic antimicrobial spectrum, MICs for five gram-positive bacterial strains and nine gram-negative bacterial strains were measured for the two types of NLS and NES combination peptides, and the results are shown in Table ​Table2.2. The highly efficient antimicrobial function of the peptide RKKKRKV RKKKRKV, the tandem sequence composed of the modified peptide from SV40 (Table ​(Table2)2) NLS (PKKKRKV), was also confirmed. It is a sequence pair where the Pro in the N terminus was replaced with Arg, showing that some rearrangement could produce better antimicrobial function in NLS/NES combination peptides. TABLE 2. MICs for combination peptides of NLS and NES for various gram-positive and gram-negative bacteria In this study, it was discovered that the antimicrobial function is inherent in the nuclear translocation signal peptide although this peptide does not originally exist for the purpose of self-defense. This is a significant difference from conventional antimicrobial peptides based on biomaterials that exist solely for self-defense (1, 2).

Elevated plasma levels of troponin I in surgical patients: analysis of risk factors and outcomes

A retrospective study of the application of troponin I assays in postoperative patients admitted to the intensive care and high dependency units in a busy district hospital was performed. Preoperative patient demographics and cardiac risk factors, prior medical history and type and urgency of surgery were correlated with the results of troponin assays: only patient gender was significantly associated, with more females having elevated serum troponin I. Outcomes were worse when troponin I was raised, with a significantly higher mortality and trend to more organ systems failed. The study was limited by small size (47 patients) and non-standardisation of the timing of troponin assay after admission. A larger prospective study needs to be performed with assays at agreed time or trigger points. The patient cohort was derived from admissions to the ICU or high dependency units (HDU) in a busy district general hospital during a 9-month period from January to September 2003. Data were collected retrospectively from the biochemistry laboratory database in order to identify those patients whose troponin I levels were assayed during this period. Serum troponin I was measured in 61 patients in the ICU or HDU setting. Of these, 14 were medical patients with myocardial infarction and were excluded from the study. The other 47 patients were surgical and they form the cohort for this study. Patients whose serum troponin was measured comprised 31 males and 16 females. Their mean age was 74 years (range 49–93, standard deviation [SD] 10 years). Among the 47 patients in whom a suspicion of myocardial dysfunction had precipitated the laboratory test, 36 had abnormally high serum levels of troponin I (troponin I > 0.05 units in our laboratory). In none of these cases had there been any demonstration of myocardial infarction on electrocardiography nor echocardiography. The remaining 11 patients were classified as having normal troponin I levels and no biochemical evidence of myocardial injury. All the patients in the normal troponin group were male, but the other cohort comprised 16 females and 20 males. This was a significant difference in sex distribution (P = 0.006, chi-squared test) (Table ​(Table11). Table 1 Analysing the outcomes of patients with raised troponin levels compared with those with normal values (summarised in Table ​Table2),2), the presence of an elevated serum troponin I was associated with a shorter duration of stay although this did not reach statistical significance (P = 0.12, unpaired t test). This contrasts with their having more organ failure as already defined: cases with abnormal serum troponin I levels had a mean of 2.0 organ systems fail during their stay in ICU/HDU, compared with 1.5 organ systems in the normal troponin I group. However, the apparent difference between the groups in numbers of organs failed did not achieve significance (P = 0.35, t test). Table 2 Among those with normal troponin tests, two of 11 patients died. This was a lower proportion than in the group with elevated serum troponin levels, in whom 13 of 36 patients died. This was statistically a highly significant difference (P < 0.001, chi-squared analysis).