The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29

Cytokines are involved in virtually every aspect of immunity and inflammation. A cascade of responses evolves after cytokine activation, although optimal function might ultimately involve several complementary cytokines. Understanding the function of individual cytokines is complicated because their role can vary depending on the cellular source, target, and phase of the immune response. In fact, numerous cytokines have both proinflammatory and anti-inflammatory potential, with the contrasting outcome observed being determined by the immune cells present and their state of responsiveness to the cytokine. These issues make the study of cytokine biology daunting, particularly so for IL-10 and IL-10-related genes. The IL-10 superfamily is highly pleiotropic. These genes are linked together through genetic similarity and intron-exon gene structure. Significant commonality exists not only through shared receptors but also through conserved signaling cascades. However, its members mediate diverse activities, including immune suppression, enhanced antibacterial and antiviral immunity, antitumor activity, and promotion of self-tolerance in autoimmune diseases.     

Percutaneous Radiofrequency Ablation of Pulmonary Metastases from Colorectal Carcinoma: Prognostic Determinants for Survival

Background Preliminary results have shown that percutaneous radiofrequency ablation (RFA) may play a useful role in patients with inoperable lung tumors. This series evaluated the prognostic features for survival in nonsurgical candidates who underwent percutaneous RFA of pulmonary metastases from colorectal carcinoma.Methods Fifty-five patients not suitable for surgery underwent percutaneous RFA for colorectal pulmonary metastases. All clinical and treatment-related data were collected prospectively. The primary end point of the study was overall survival, defined from the time of RFA intervention. Univariate and multivariate analyses were performed to identify statistically significant prognostic parameters for overall survival.Results The overall median survival was 33 months (range, 4–40 months), with actuarial 1-, 2-, and 3-year survival of 85%, 64%, and 46%, respectively. Univariate analysis demonstrated that largest size of lung metastasis (P < .001), location of lung metastases (P = .032), and repeat percutaneous RFA for pulmonary recurrence (P = .024) were statistically significant for overall survival. Multivariate analysis demonstrated that largest size of lung metastasis >3 cm was independently associated with a reduced overall survival (P = .003).Conclusions Percutaneous lung RFA may play a useful role in nonsurgical candidates with colorectal pulmonary metastases. However, the survival benefit of this interventional procedure for patients with a pulmonary metastasis >3 cm was limited.     

NO- and haem-independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle

1. Soluble guanylyl cyclase (sGC) is the only proven receptor for the ubiquitous biological messenger nitric oxide (NO) and is intimately involved in many signal transduction pathways, most notably in regulating vascular tone and platelet function. sGC is a heterodimeric (alpha/ss) protein that converts GTP to cyclic GMP; NO binds to its prosthetic haem group. Here, we report the discovery of a novel sGC activating compound, its interaction with a previously unrecognized regulatory site and its therapeutic implications. 2. Through a high-throughput screen we identified BAY 58-2667, an amino dicarboxylic acid which potently activates sGC in an NO-independent manner. In contrast to NO, YC-1 and BAY 41-2272, the sGC stimulators described recently, BAY 58-2667 activates the enzyme even after it has been oxidized by the sGC inhibitor ODQ or rendered haem deficient. 3. Binding studies with radiolabelled BAY 58-2667 show a high affinity site on the enzyme. 4. Using photoaffinity labelling studies we identified the amino acids 371 (alpha-subunit) and 231 - 310 (ss-subunit) as target regions for BAY 58-2667. 5. sGC activation by BAY 58-2667 results in an antiplatelet activity both in vitro and in vivo and a potent vasorelaxation which is not influenced by nitrate tolerance. 6. BAY 58-2667 shows a potent antihypertensive effect in conscious spontaneously hypertensive rats. In anaesthetized dogs the hemodynamic effects of BAY 58-2667 and GTN are very similar on the arterial and venous system. 7. This novel type of sGC activator is a valuable research tool and may offer a new approach for treating cardiovascular diseases.     

Using prescribing health and population data to describe the health of a locality: the development and evaluation of a locality health profile

Objective To develop and evaluate a pharmaco‐epidemiological and public health profile that will aid in the determination and evaluation of the health and pharmaceutical needs of a local population with the National Health Service (NHS). Method Two local health areas (known as local health care co‐operatives (LHCCs)) in NHS Lothian with diverse population characteristics had health profiles formally developed using prescribing, hospitalisation and other public health data. The integrated report was able to highlight morbidity issues in each LHCC that could be acted on by either LHCC management or local pharmacy groups. A steering committee and focus groups were used in the design and evaluation process. An evaluation survey of participants including LHCC management, community and LHCC pharmacists and other healthcare professionals was conducted with the main outcome measure being the relative utility of the health profile. Key findings Participants evaluating the health profiles found them informative and useful in decision making and planning for the locality. Participants anticipated using prescribing data to fill information gaps in other datasets and/or provide a primary care perspective to health in the locality. Conclusions Health profiles were developed from prescribing health and population data that were shown to be meaningful and useful to local health authority management and other healthcare professionals. The health profiles contained information that could be used to inform decisions or identify areas where further investigation may be required to find out why a particular anomaly is occurring. In Scotland, the focus of a new community pharmacy contract is on the dual elements of chronic disease management and public health contributions, through prevention of disease and/or limitation of disease impact. There is an urgent need to develop tools that help to inform professional interventions involving pharmacists, and thereby improvements to multidisciplinary co‐operation. This study suggests a means of describing the population characteristics for informing a network of community pharmacists about public health priorities within their LHCC.     

Controlled study of inline radiofrequency ablation (ILRFA) assisted transection of ovine liver

BACKGROUND: Liver resection is now a standard treatment for primary and secondary hepatic tumors around the world. Intra-operative blood loss during liver resection is a major factor associated with morbidity and mortality. We have developed a new instrument using radiofrequency energy (ILRFA), which is intended to achieve coagulative ablation in a plane. This plane can then be cut through with a scalpel, ultrasonic dissector, or diathermy with minimal blood loss. MATERIALS AND METHODS: Five sheep were used in this non-recovery experiment. In these sheep we performed five liver resections with the ILRFA and five similar resections using diathermy and suturing as control. Blood loss was measured by determining the difference in the weights of dry sponges and blood stained sponges after resection. RESULTS: ILRFA was successful in achieving coagulative ablation in all cases to a width of 1 cm. The mean blood loss in ILRFA was 43.2 g (SD36) and 221.8 g (SD147) in the control group. The bleeding was significantly reduced in ILRFA group with a P value of 0.005. CONCLUSIONS: Bleeding remains an important complication of liver resection. To reduce bleeding during liver surgery, different techniques have been used. In this study, we have demonstrated that by using ILRFA we can perform liver resections in sheep with minimal blood loss.     

Intimacy needs and chronic illness: strategies for sexual counseling and self-management

Individuals experiencing a chronic illness have many needs and concerns. One area frequently overlooked is that of intimacy. Those experiencing cardiovascular illnesses have concerns about the strain of sexual activity on their heart. Individuals with lung diseases may perceive that sexual activity is no longer possible because of breathing difficulties. Accurate information and strategies for self-management are needed to address the intimacy needs and concerns of these individuals. The purpose of this article is to identify intimacy needs and strategies for sexual counseling for individuals with cardiovascular illnesses such as myocardial infarction, heart failure, implantable defibrillators, hypertension, and for chronic lung problems.     

Protein quality comparison of a new isolated soy protein and milk in chilean preschool children

The protein quality of a newly developed soybean protein isolate (SPF-200) and milk were compared using apparent N digestibility (AND), N balance (ANB) and serum biochemical response to graded levels of N intake (NI). Seven healthy well nourished children aged 35 to 62 months, were given for 8 day periods 1.5, 1.25, 1.0 and 0.75 g protein/kg/day of SPF and milk in decreasing order at a constant energy intake of 100 Kcal/kg/day and a vitamin mineral supplement. AND for SPF ranged from 86 to 70% and for milk 83 to 75%, corresponding to highest and lowest NI, ANB for SPF ranged from 63 to 0 mg/kg/day and for milk from 90 to 28 mg/kg/day. Mean individual regressions of daily ANB and NI were ANB=0.49 NI-54 for SPF and ANB=0.51 NI-34 milk. The slopes were not significantly different. Non significant decreases in serum albumin and urea were observed. A°significant increases in transaminases was noted at the lowest NI for both proteins. Daily protein allowances to retain 39 mg N/kg/day were 1.27 and 0.91 g protein/kg/day for SPF and milk respectively.