Ca2+ sensors modulate asthmatic symptoms in an allergic model for asthma

We previously described two novel peptides, Ca2+-like peptide (CALP) 1 and CALP2, which interact with Ca2+-binding EF hand motifs, and therefore have the characteristics to define the role of the Ca2+-sensing regulatory protein calmodulin in asthma. In the present study, the effects of the calcium-like peptides were investigated in an animal model for allergic asthma. For that purpose, sensitized guinea pigs were intratracheally pretreated with CALP1 or CALP2. Thirty minutes later, the animals were challenged with aerosolized ovalbumin. Acute bronchoconstriction was measured as well as characteristic features of asthma 6 and 24 hours (h) after challenge. Neither CALP1 nor CALP2 prevented the anaphylactic response elicited by ovalbumin challenge. However, CALP1 pretreatment attenuated the influx of inflammatory cells in the lungs 6 h after challenge. Furthermore, radical production by these cells was diminished both 6 and 24 h after challenge. Moreover, CALP1 completely inhibited airway hyperresponsiveness in vitro 24 h after challenge. We conclude that CALP1, as a selective calmodulin agonist, inhibits the development of asthmatic features probably via the attenuation of mast cell degranulation and radical production. Specific modulation of calmodulin activity might therefore be a potential new target for the treatment of allergic asthma.     

A pilot study of plasma caffeine concentrations in a US sample of smoker and nonsmoker volunteers

Even though 85% of adults drink caffeinated beverages daily, very limited studies on plasma caffeine concentration in the US population have been published. Smoking induces cytochrome P450 1A2 (CYP1A2), which is the main enzyme involved in caffeine metabolism. The current naturalistic pilot study explores plasma caffeine concentrations in a US sample, and presents a mathematical model of the relationship between caffeine intake and plasma concentrations for smokers and nonsmokers. Caffeine intake and average plasma caffeine concentrations from morning (7:30-9:30 a.m.) and afternoon (2:00-4:00 p.m.) samples were studied in 69 volunteers (21 smokers and 48 nonsmokers). The mean caffeine intake obtained from caffeinated beverages was 3.02 mg/kg/day, which is similar to the intake in the US population. Almost all subjects in the present sample (99%; 95% confidence interval [CI]: 96-100) had detectable plasma caffeine concentrations. Smokers had significantly higher caffeine intake than nonsmokers. The ratio of concentration/dose of caffeine from caffeinated beverages was approximately four-fold higher in nonsmokers (1.33 kgxday/l) than in smokers (0.29 kgxday/l). According to the model, the median plasma caffeine concentration was two- to three-fold higher in nonsmokers for each level of caffeine intake. Our model improves our understanding of the interactions between caffeine and smoking. Additional studies are needed to replicate the model. This model may help epidemiologists to correct for the effects of smoking on caffeine intake and pharmacologists to screen for the activity of CYP1A2.     

Importance of minor histocompatibility antigen expression by nonhematopoietic tissues in a CD4+ T cell-mediated graft-versus-host disease model

Minor histocompatibility antigens with expression restricted to the recipient hematopoietic compartment represent prospective immunological targets for graft-versus-leukemia therapy. It remains unclear, however, whether donor T cell recognition of these hematopoietically derived minor histocompatibility antigens will induce significant graft-versus-host disease (GVHD). Using established bone marrow irradiation chimeras across the multiple minor histocompatibility antigen-disparate, C57BL/6-->BALB.B combination, we studied the occurrence of lethal GVHD mediated by CD4+ T cells in recipient mice expressing only hematopoietically derived alloantigens. Even substantial dosages of donor C57BL/6 CD4+ T cells were unable to elicit lethal GVHD when transplanted into [BALB.B-->C57BL/6] chimeras. Instead, chimeric mice displayed transient cachexia with reduced target-tissue injury over time, reflecting an early, limited, graft-versus-host response. On the other hand, the importance of minor histocompatibility antigens derived from nonhematopoietic tissues was demonstrated by the finding that [C57BL/6-->BALB.B] chimeric mice succumbed to C57BL/6 CD4+ T cell-mediated GVHD. These data suggest that severe acute CD4+ T cell-mediated GVHD across this minor histocompatibility antigen barrier depends on the expression of nonhematopoietically rather than hematopoietically derived alloantigens for maximal target-tissue infiltration and injury.     

Hypervitaminosis B12 in maintenance hemodialysis patients receiving massive supplementation of vitamin B12

We have administered routinely a multivitamin preparation containing a megadose of B12 to 106 hemodialysis patients after dialysis treatments. We found that these patients had very high levels of serum vitamin B12 which returned to original values only after a period of three years after stopping the vitamin. Discontinuing therapy had no effect on hemoglobin, mean erythrocyte corpuscular volume, or motor nerve conduction velocity. It is not known whether maintaining a prolonged high level of vitamin B12 is harmful. However, animal and epidemiologic studies have suggested that both cobalamin and cobalt may be potentially toxic. In view of the absence of demonstrable benefit and the possible risk of toxicity, we believe that the use of such megadose vitamin compounds in dialysis patients should be re-evaluated.     

Alterations in the vimentin cytoskeleton in response to single impact load in an <Emphasis Type="Italic">in vitro</Emphasis> model of cartilage damage in the rat

Background  

Animal models have provided much information on molecular and cellular changes in joint disease, particularly OA. However there are limitations to in vivo work and single tissue in vitro studies can provide more specific information on individual events. The rat is a commonly used laboratory species but at the current time only in vivo models of rat OA are available to study. The purpose of this study was to investigate the damage that single impact load (SIL) of 0.16J causes in a rat cartilage in vitro model and assess whether this load alters the arrangement of vimentin.     

Regional anaesthesia versus general anaesthesia--pathophysiology and clinical implications

Regional anaesthesia is well established in modern clinical practice. It provides a safe and reliable alternative to general anaesthesia, but is also of high clinical value in combination procedures. Our knowledge of perioperative pathophysiological characteristics increasingly indicates that regional blocks lead to excellent analgesia und profoundly modulate the postoperative stress response and thus, they can have therapeutic influence on postoperative convalescence, on the functional operation result and on the avoidance of frequent postoperative complications. Given the increasing number of older patients with nigher co-morbidity, this is of particular therapeutic importance, but also has economic implications. The continuous techniques of regional anaesthesia, which at first sight are more time-consuming and expensive, may shorten the time to extubation after major abdominal procedures, accelerate postoperative recovery and prevent postoperative adverse outcomes. Optimised physiotherapy after total knee arthroplasty or improvements in pulmonary and gastrointestinal function demonstrate the capabilities of regional anaesthesia to facilitate postoperative rehabilitation. With regard to an improved organ function and a possibly shorter hospital stay, regional techniques appear cost-effective. It is important that regional anaesthesia is carried out on the basis of a clear individual indication, which considers the entire perioperative treatment process.     

Electromagnetic Interference (EMI) and arrhythmic events in ICD patients undergoing gastrointestinal procedures

BACKGROUND: The objective was to determine the effect of electromagnetic interference (EMI) in patients undergoing gastrointestinal endoscopy. The implantable cardioverter-defibrillator (ICD) is the primary therapeutic modality for patients at risk for sudden cardiac death. One potential problem with ICDs is interactions with electrical devices and medical procedures causing EMI or triggering arrhythmic events. Endoscopy frequently employs electrocautery (EC) for diagnosis and treatment of gastrointestinal diseases. Current guidelines advise inactivating ICDs before any surgical procedure. There is limited information on management of ICDs during endoscopy with or without EC. We prospectively evaluated patients with ICDs undergoing endoscopic procedures at our institution. METHODS AND RESULTS: Forty-one ICD patients underwent 52 gastrointestinal endoscopies over 17 months. The mean age of the population was 66 years (51-83). There were 28 men and 13 women. Thirteen patients had single chamber devices, 25 had dual chamber devices, and 2 had biventricular ICDs. The mean tachyarrhythmia detection rate programmed was 164.7 bpm (125-188). Eighteen procedures (43.9%) required biopsy, coagulation, or polypectomy. Of these, 10 (55%) required the use of EC. Only unipolar EC with mean current 19.6 mA was used. All ICDs were programmed to detection-only with therapies off. Sensitivity was left at nominal programmed settings. Post procedure interrogation showed no detection of EMI or tachyarrhythmic events. CONCLUSIONS: Our study shows no EMI or arrhythmic events triggered during endoscopic procedures in patients with pectorally implanted transvenous ICDs. Routine practice of programming ICDs off for gastrointestinal procedures may not be necessary. However, larger studies are needed before change in current recommendations.     

Health for all Australians

This paper explores some of the social and political factors that have influenced the way in which the Australian health care system has developed, and the models it uses to deliver health care. This information is used to suggest changes that need to be made to health policy and the health care system in order to provide equitable access and efficient service to all Australians. The example of persons who have contracted Hepatitis C via injecting drug use is used to illustrate the arguments.     

Nephrotoxicity After the Treatment of Periprosthetic Joint Infection With Antibiotic-Loaded Cement Spacers

Background

Treatment of periprosthetic joint infections commonly involves insertion of an antibiotic-loaded cement spacer (ACS). The risk for acute kidney injury (AKI) related to use of antibiotic spacers has not been well defined. We aimed to identify the incidence of and risk factors for AKI after placement of an ACS.