The role of the complement anaphylatoxins in the recruitment of eosinophils

Eosinophils are blood and tissue immune cells that participate in a diverse range of activities normally beneficial for the host defense, but in circumstances of untoward inflammatory conditions these cells can be responsible for pathological responses. Accordingly the transit of eosinophils from the blood to tissues is a subject of considerable importance in immunology. In this article we review how the complement anaphylatoxins, C3a and C5a bring about eosinophil extravasation. These mediators do not merely provide a chemotactic or haptotactic gradient but are responsible for orchestrating innumerable responses by other cells types, including of endothelial cells, mast cells, and basophils in order to create an environment that is conducive for eosinophil infiltration. C5a has the capacity to prime the endothelium directly to present P-selectin, and C5a stimulated generation of eosinophil hydrogen peroxide and other oxidants can cause additional upregulation of endothelial P-selectin and ICAM-1. Moreover, the anaphylatoxins have the ability to recruit mast cells and basophils and can stimulate these cells to release IL-4 and IL-13, which by augmenting endothelial VCAM-1, convey some selectivity for eosinophils. The anaphylatoxins also have the capability to evoke the release and activation of eosinophil MMP-9, which is employed by this cell type to digest its way past the subendothelial matrix. Finally, because C3a and C5a can stimulate the generation of nitric oxide along with the secretion of histamine and LTC4 from several cell types, the anaphylatoxins can bring about an increase in vascular permeability that facilitates eosinophil accumulation at sites of allergic inflammation.     

The role of infections in the pathogenesis of autoimmune diseases

The autoimmune diseases result from inappropriate responses of the immune system to self antigens. The etiology of autoimmune diseases remains largely unknown but candidate etiologic factors include genetic abnormalities and infections. Although there are considerable data supporting the role of infections in a variety of autoimmune diseases, this role has been unequivocally established in only a few autoimmune diseases. The difficulty in establishing the infectious etiology of autoimmune diseases stems from several factors such as the heterogeneity of clinical manifestations in individual autoimmune diseases and the time interval between infection and autoimmune disease. The data on this association derive from clinical observations, epidemiological studies and research using laboratory techniques, protein sequence database screening and animal models. Infectious agents can cause autoimmune diseases by different mechanisms, which fall into two categories: antigen specific in which pathogen products or elements have a central role e.g. superantigens or epitope (molecular) mimicry, and antigen non-specific in which the pathogen provides the appropriate inflammatory setting for "bystander activation". The most important mechanisms are molecular mimicry and superantigens. As far as molecular mimicry is concerned the recent data on the degeneracy of T cell recognition shifted the focus from searching for linear sequence homology to looking for similarity of antigenic surfaces. Special mention has to be made to retroviruses as they have some unique means of inducing autoimmunity.     

The role of telavancin in the treatment of MRSA infections in hospital

Background: Serious infections caused by Gram-positive bacteria, particularly multi-drug resistant, are an important cause of morbidity and mortality in patients admitted to intensive care units. Thus, new antibiotics covering these pathogens are urgently needed. Objective: To review characteristics of telavancin, a novel antibiotic intended to use for treating infections caused by difficult Gram-positive bacteria, such as Staphylococcus aureus, resistant to meticillin or vancomycin, multi-drug-resistant Streptococcus pneumoniae or glycopeptide-resistant enterococci. Methods: The studies on microbiological activity, clinical efficacy and safety of telavancin were reviewed. Results/conclusion: Telavancin is a lipoglycopeptide administered intravenously once-daily and excreted with urine. It proved to be microbiologically active against numerous Gram-positive pathogens including drug-resistant staphylococci, enterococci and pneumococci. Large randomized Phase II and III clinical trials on efficacy and safety of telavancin in treating complicated skin and skin structure infections reported telavancin to be non-inferior to standard treatment (mostly vancomycin). Preliminary data on telavancin in hospital-acquired pneumonia, including ventilator-associated pneumonia, documented that telavancin was efficacious for this indication. Overall incidence of adverse events was similar for telavancin and the comparator arms. Mild and transient disgeusia, nausea and vomiting resulted to be more frequent in telavancin group. Increase in creatinine values was also observed in telavancin arm.     

The potential role of nemonoxacin for treatment of common infections

Introduction: Nemonoxacin, a novel non-?uorinated quinolone, exhibits potent activity against Gram-positive bacteria, including MRSA and fluoroquinolone-resistant MRSA, Gram-negative and atypical pathogens. This agent also has a reduced propensity for resistance development in many kinds of pathogens.

Areas covered: This article reviews currently available clinical and in vitro data that support the potential role of nemonoxacin for the treatment of common infectious diseases, including community-acquired pneumonia (CAP), Clostridium difficile infections (CDIs), acute bacterial skin and skin structure infections (ABSSSIs) and sexually transmitted diseases (STDs). One recent Phase II trial comparing either 500 mg or 750 mg oral nemonoxacin with 500 mg oral levofloxacin for mild to moderate CAP demonstrated that nemonoxacin had comparable clinical success with levofloxacin. Nemonoxacin showed lower MICs against clinical C. difficile isolates than commercially available fluoroquinolones, making it a potential therapeutic agent if novel formulations are developed to maintain a higher concentration in the human gut. For STDs, nemonoxacin also showed good activity against some common pathogens, such as Chlamydia trachomatis and Neisseria gonorrhoeae.

Expert opinion: Although in vitro studies have shown promising results regarding the susceptibility to nemonoxacin of common pathogens causing CDIs, ABSSSIs and STDs, further clinical trials are needed to prove its efficacy.     

浅谈基础护理在预防和控制院内感染中的作用

目的做好基础护理工作,降低医院感染率。方法提高护理人员的职业素质,加强基础护理操作。结果医院感染率由1996年的7%降到2008年的4%。结论卫生部制定了三级监控,强调预防为主。在医院,护士接触患者最频繁,提高护理人员的职业素质,坚持护理操作规范化、合理化、科学化,重点搞好基础护理,是预防和控制院内感染的关键措施之一。     

The role of fluoroquinolones in respiratory tract infections: community acquired pneumonia

Newer fluoroquinolones may play an important role in the management of community acquired pneumonia. They retain activity similar to older fluoroquinolones against Gram-negative bacteria and are significantly more active against Gram-positive bacteria, especially pneumococci. They are also active against bacteria causing atypical pneumonia, penicillin-sensitive and -resistant and macrolide-sensitive and -resistant pneumococci and against beta-lactamase producing and non-producing Haemophilus influenzae. They have similar or slightly lower activity than ciprofloxacin against other Gram-negative organisms. They have rapid bactericidal activity and attain good lung tissue levels. Clinical studies show results similar or better than older treatments. Their impact on ecology and resistance remains to be elucidated but data on side effects and toxicity must be carefully evaluated.     

The role of carbapenems in the treatment of severe nosocomial respiratory tract infections

The prevalence of antibiotic-resistant bacteria continues to increase, particularly in patients in the intensive care unit with nosocomial pneumonia. The intention of this review is to provide an overview of severe nosocomial pneumonia, carbapenems and the problem of bacterial resistance to antimicrobial agents. Attention was focused on the efficacy, safety and pharmacodynamics of imipenem, meropenem, ertapenem and doripenem. Issues on the impact of appropriate empiric antibiotic therapy for nosocomial pneumonia patients considered at risk for resistant pathogens are discussed. Critical decision making regarding the use of carbapenems for treating severe nosocomial pneumonia requires careful consideration of the four Ds of optimal antimicrobial therapy: right Drug, right Dose, De-escalated to pathogen-directed therapy and right Duration of therapy.     

The role of antibodies against hsp90 in the treatment of fungal infections

Advances in antibody engineering have solved many of the problems inherent in traditional sources of antibodies, and about a quarter of all biotechnology-based drugs now in development are antibodies. This has come at a time when it is apparent that reliance on antibiotics alone is beginning to select out resistant pathogens, fungi being a prime example. The development of antibody-based therapeutics, such as Mycograb, against novel fungal targets offers a new approach to combating the spread of resistance and reducing mortality.     

Cefepime and its role in pediatric infections

Cefepime is a semi-synthetic fourth generation cephalosporin with broader Gram-positive and excellent Gram-negative bacterial coverage. Its extended anti-microbial activity and infrequent tendency to develop resistance makes it popular for treatment of infections due to multi-drug resistant organisms. It has good efficacy against beta-lactamase and ESBL (extended spectrum beta-lacatamase)-secreting pathogens, and it has shown great promise in management of children with severe and nosocomial infections. It possesses superior bactericidal action compared to other cephalosporins and is a cheaper and safe alternative to the carbapenems. It is well-tolerated but needs dose adjustments in newborns, and in children with renal insufficiency. Cefepime is a valuable antibiotic but it should be used judiciously as unnecessary, improper and prolonged use may lead to emergence of cefepime-insensitive bacteria and risk of drop in the efficacy of cefepime. Various recent patents of cefepime have been launched which deal with improvements in its preparation, and with its combinations with beta-lactamase inhibitors and newer antibiotics such as linezolid. These developments may further augment the usefulness of cefepime in pediatric infections.     

Impairment of drug metabolism in polycystic non-parasitic liver disease.

1. Drug-metabolizing capacity in cases of polycystic non-parasitic liver disease was investigated using plasma antipyrine clearance as an index. 2. The four subjects with maternally inherited polycystic liver metabolized antipyrine at a significantly slower rate than the six other members of the family. 3. This reduction in antipyrine metabolism is due to the loss of active liver parenchyma, and is probably also influenced by alterations in the vascular bed due to compression by the enlarged cysts.     

The nature and role of microbial biofilm in infections associated with prosthetic devices

An understanding of the role of microbial biofilm in infections associated with prosthetic devices is essential for the implementation of successful treatment regimens.     

The current role of amphotericin B lipid complex in managing systemic fungal infections

Abstract

Background:

An increase in the number of immunocompromised patients has led to a rising burden of systemic fungal infections. Historically, conventional amphotericin B has been used to treat these infections due to its broad spectrum of activity. The development of lipid-based amphotericin B agents, such as Abelcet^* (ABLC), has allowed clinicians to take advantage of the broad spectrum of activity of amphotericin B while reducing adverse events. As well as this, a number of new antifungal agents have been developed in recent years which have significantly added to the treating physician’s antifungal armamentarium.     

The pro-apoptotic effect of hydroquinone in human neutrophils and eosinophils

Hydroquinone (HQ) is a benzene metabolite that is involved in hematopoiesis via its accumulation into bone marrow. HQ also acts as a toxic agent that influences various immune responses. Both neutrophils and eosinophils function as important leukocytes in immunological regulation and immune diseases. In this study, we examined the toxic effects of HQ on the apoptosis of human neutrophils and eosinophils isolated from the blood of healthy donors. HQ markedly increased the apoptosis of neutrophils and eosinophils in a concentration- and a time-dependent manner. The pro-apoptotic effect is involved in activation of caspase 9 and caspase 3. Reactive oxygen species (ROS) production was enhanced after HQ treatment in a dose-dependent manner. In addition, HQ upregulated the release of IL-8 and MCP-1 from neutrophils and eosinophils, respectively. Taken together, the results of this study demonstrated that HQ strongly induces the apoptosis of neutrophils and eosinophils through the caspase 9/3-dependent pathway and the increased ROS production. HQ exerts a cytotoxic effect in human neutrophils and eosinophils and may impair the regulation of immune responses.     

糖皮质激素对鼻息肉组织中嗜酸粒细胞的调控作用

目的探讨嗜酸粒细胞与鼻息肉的关系以及糖皮质激素对鼻息肉中嗜酸粒细胞的影响。方法采用HE染色，检测60例鼻息肉组织和鼻喷布地奈德（400μg／d）后30例鼻息肉组织中嗜酸粒细胞数，并进行比较。结果鼻息肉组织中嗜酸粒细胞计数明显高于鼻喷布地奈德2周后的鼻息肉组织，激素组与鼻息肉未治疗组相比差异有显著意义（P〈0．01）。结论嗜酸粒细胞浸润程度与鼻息肉发展相关．糖皮质激素可能通过对嗜酸粒细胞浸润程度的调控发挥其治疗作用。     

Solitary symptomatic non-parasitic cyst of liver presenting as pancreatic pseudocyst

A case of a solitary symptomatic non-parasitic cyst of the liver, was seen and treated at the Muhimbili Medical Centre, Dar Es Salaam. This is the first case report from Tanzania, cystic disease of the liver is rarely diagnosed clinically, the possibility should be seriously considered in any patient with an enlarged liver which is associated with few or no symptoms and little or no impairment of liver function. In African countries, it is suggested that non-parasitic cysts of the liver be considered in the differential diagnosis of hepatocellular carcinoma because of its high prevalence rate in these countries.