Chemokines: Their role in rheumatoid arthritis

Chemokines are small proteins that can act on cells that express matching receptors. They are best known for their role in migration of cells, especially immune cells. Chemo-kine/ chemokine-receptor pairs are often functionally cate-gorized into three groups: inflammatory, homeostatic, and angiogenic/angiostatic, although functions sometimes over-lap. Interfering with the interaction between chemokines and their receptors is currently under investigation as a therapeutic strategy in rheumatoid arthritis.     

Evaluation of prognostic indexes in critical acute renal failure patients

OBJECTIVE: To study different prognostic indexes in acute renal failure (ARF) patients admitted to an intensive care unit (ICU). DESIGN: Prospective, cohort study. Individual Severity Score-Acute Tubular Necrosis (ISS-ATN) obtained prospectively and retrospectively, Acute Physiologic and Chronic Health Evaluation (APACHE II) Score, APACHE II Risk, Lung Injury Score (LIS), and Number of Organ Failures (NOF) were calculated for each patient. The outcome analyzed was death in the ICU. Discrimination was evaluated by the area under the receiver operator characteristic curve (AUC). For calibration analysis, the chi-square goodness-of-fit test was used to compare predicted mortality, calculated by ISS-ATN (obtained prospectively or retrospectively) and APACHE II risk, with observed mortality. SETTING: ICU, S?o Rafael Hospital, Salvador-BA, Brazil. PATIENTS: Seventy-six ARF patients admitted to the ICU within 6 months. INTERVENTIONS: Surgical and medical procedures. MEASUREMENTS AND RESULTS: The observed AUC was 0.69 for LIS, 0.73 for prospective ISS-ATN, 0.75 for retrospective ISS-ATN, 0.76 for APACHE II Score, 0.78 for APACHE II Risk, and 0.88 for NOF. These areas were significantly different from 0.5 (p < .001). There was no difference between the observed and expected death rate calculated by ISS-ATN. However, APACHE II underestimated the observed mortality (p < .001). CONCLUSION: The prognostic indexes studied showed good discriminative power. However, APACHE II was not well calibrated in contrast to the good calibration of ISS-ATN.     

A quality-of-life study in high-risk (thickness > = or 2 mm) cutaneous melanoma patients in a randomized trial of 1-cm versus 3-cm surgical excision margins

A quality-of-life study was carried out to test the hypothesis that melanoma patients treated with a 3-cm margin of excision suffer greater impairment of their quality of life than those treated with a 1-cm margin. The secondary aim was to determine the predictors of a poor patient perception of their excision scar. A postal questionnaire study was carried out using Hospital Anxiety and Depression (HAD), Psychosocial Adjustment of Illness Scale-Self-Report (PAIS-SR), Medical Outcomes Survey-Short Form 36 (MOS-SF36), and the Cassileth Scar questionnaires. Data were collected from 426 of the 537 patients who were mailed the questionnaires (response rate 79%). Fourteen percent had clinically significant anxiety and 5% had significant depression. A poor attitude toward quality of health care was associated with youth. Patients treated with a 3-cm margin excision had significantly poorer mental and physical function 1 mo after surgery, which disappeared within 6 mo. The greater difficulties experienced by the 3-cm margin group were particularly in their domestic, sexual, and social roles. Women, younger patients, those with poor physical and mental function after surgery, and those treated by a 3-cm margin were more likely to report a poorer perception of their scar. The poorer scar perception of patients in the 3-cm group persisted throughout the study period. Use of a 3-cm margin of excision for melanoma is associated with significantly more morbidity than use of a 1-cm margin, but this effect disappears in 6 mo. Patients treated by 3-cm excision were more likely, however, to have a persistent poor view of their scar. Youth and being female were also predictors of poor perception of the scar.     

HPLC-based activity profiling of Salvia miltiorrhiza for MAO A and iNOS inhibitory activities

In the course of a screening of plant extracts for potential CNS and anti-inflammatory activities, a dichloromethane extract of Salvia miltiorrhiza showed a pronounced inhibitory effect on recombinant monoamine oxidase A (MAO A) and on inducible NO synthase (iNOS) induction in Raw 267.4 cells. With the aid of HPLC-based profiling techniques, activities could be linked, to a significant extent, to peaks of tanshinone-type diterpenoids, four of which were subsequently isolated. The IC50 of the most active compound, 15,16-dihydrotanshinone I, on human recombinant MAO A was at 23 microM, and 2.4 microM on lipopolysaccharide-mediated iNOS induction in Raw 267.4 cells.     

From the Cover: Thuricin CD,a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile

The last decade has seen numerous outbreaks of Clostridium difficile-associated disease (CDAD), which presented significant challenges for healthcare facilities worldwide. We have identified and purified thuricin CD, a two-component antimicrobial that shows activity against C. difficile in the nanomolar range. Thuricin CD is produced by Bacillus thuringiensis DPC 6431, a bacterial strain isolated from a human fecal sample, and it consists of two distinct peptides, Trn-α and Trn-β, that act synergistically to kill a wide range of clinical C. difficile isolates, including ribotypes commonly associated with CDAD (e.g., ribotype 027). However, this bacteriocin thuricin CD has little impact on most other genera, including many gastrointestinal commensals. Complete amino acid sequencing using infusion tandem mass spectrometry indicated that each peptide is posttranslationally modified at its respective 21st, 25th, and 28th residues. Solution NMR studies on [¹³C,¹⁵N] Trn-α and [¹³C,¹⁵N]Trn-β were used to characterize these modifications. Analysis of multidimensional NOESY data shows that specific cysteines are linked to the α-carbons of the modified residues, forming three sulfur to α-carbon bridges. Complete sequencing of the thuricin CD gene cluster revealed genes capable of encoding two S′-adenosylmethionine proteins that are characteristically associated with unusual posttranslational modifications. Thuricin CD is a two-component antimicrobial peptide system with sulfur to α-carbon linkages, and it may have potential as a targeted therapy in the treatment of CDAD while also reducing collateral impact on the commensal flora.