Experimental colitis reduces microglial cell activation in the mouse brain without affecting microglial cell numbers.

Inflammatory bowel disease (IBD) patients frequently suffer from anxiety disorders and depression, indicating that altered gut-brain axis signalling during gastrointestinal inflammation is a risk factor for psychiatric disease. Microglia, immune cells of the brain, is thought to be involved in a number of mental disorders, but their role in IBD is largely unknown. In the current work, we investigated whether colitis induced by dextran sulphate sodium (DSS), a murine model of IBD, alters microglial phenotypes in the brain. We found that colitis caused a reduction of Iba-1 and CD68 immunoreactivity, microglial activation markers, in specific brain regions of the limbic system such as the medial prefrontal cortex (mPFC), while other areas remained unaffected. Flow cytometry showed an increase of monocyte-derived macrophages during colitis and gene expression analysis in the mPFC showed pronounced changes of microglial markers including cluster of differentiation 86 (CD86), tumour necrosis factor-α, nitric oxide synthase 2, CD206 and chitinase-like protein 3 consistent with both M1 and M2 activation. Taken together, these findings suggest that experimental colitis-induced inflammation is propagated to the brain altering microglial function.

Nosocomial infections in leukemic and solid-tumor cancer patients: distribution, outcome and microbial spectrum of anaerobes.

AIMS: Nosocomial infections cause significant morbidity and mortality in cancer patients. As a result of their debilitated immune system, cancer patients are likely candidates for colonization with anaerobes. We sought to compare the distribution of nosocomial infections in neutropenic and non-neutropenic cancer patients and to calculate the associated mortality rates. MATERIAL & METHODS: This is the first study to demonstrate a complete microbial spectrum of anaerobes in various infection sites in hospitalized cancer patients. RESULTS: Frequencies of bloodstream infections (BSI), respiratory tract infections (RTI), and GI tract infections (GITI) were significantly higher in neutropenic cancer patients (p < 0.01). Conversely, urinary tract infection (UTI) and skin infection (SI) rates were significantly higher in non-neutropenic cancer patients (p < 0.01). Mortalities attributed to BSI, UTI, RTI, SI, and GITI occured at the respective percentage frequencies of 12.5%, 11.5%, 10.4%, 7.7% and 4.9%. Anaerobes constituted 4.7% of total isolates, and were recovered from SI (66.3%) and GITI (33.6%), but not respiratory tract, urine, or blood. Most anaerobes (79.2%) were isolated from solid-tumor patients. The most common infection in cancer patients was RTI (55.8%), mainly in leukemic patients, followed by SI (18%), only in solid-tumor patients, GITI (9.7%), BSI (9.4%), and UTI (7.1%). The most frequent isolates of Fusobacterium necrophorum (32.7%) and Eubacterium lentum (23.8%) were mostly recovered from solid-tumor patients. These were followed by Clostridium perfringens (11.9%), Clostridium difficile (10.9%), Eubacterium limosum (5.9%), and Veillonella parvula (5%). CONCLUSION: Control measures are needed to minimize risks of nosocomial infection outbreaks by anaerobes. Continuous monitoring of the presence of anaerobes in various infection sites in hospitalized cancer patients is needed in order to be able to provide the best supportive care for cancer patients.

Curcumin immune-mediated and anti-apoptotic mechanisms protect against renal ischemia/reperfusion and distant organ induced injuries.

Renal ischemia followed by reperfusion results in kidney injury which in turn produces and releases destructive inflammatory cytokines into the circulation causing subsequent distant organ injury. Little data suggest the immune mechanism of curcumin on protection against ischemia/reperfusion induced injury. We investigated the immunomodulatory and anti-apoptotic effects of curcumin on ischemia/reperfusion (I/R) injury in rats. Thirty-six rats were randomly divided into three experimental groups (sham, I/R and curcumin pretreated I/R, n=12 each). Curcumin was administered orally to curcumin pretreated I/R group. Curcumin can significantly decrease both systemic as well as blood levels of cytokines (p<0.05). Treatment with curcumin also resulted in significant reduction in serum and tissue level of TNF-α, IL-1ß, IL-12, IL-18 and INF-γ that were increased by renal I/R injury (p<0.05). Curcumin pretreatment reduce pulmonary apoptotic pathway via significant inhibition of TGF-ß and caspase-3 in kidney and lung tissues. Given that pulmonary apoptosis is an important complication of acute renal injury, we identified curcumin protective effect against distant organ I/R induced injury. Based on our results, we concluded that curcumin protects the kidneys and other vital organs against I/R injury via immune-mediated and the new identified anti-apoptotic mechanisms.

Chitosan-EDTA new combination is a promising candidate for treatment of bacterial and fungal infections.

Chitosan is an attractive preparation widely used as a pharmaceutical excipient. This study aimed to evaluate the antimicrobial activities of chitosan derivatives, EDTA, and the newly developed chitosan-EDTA combination against Gram-negative and Gram-positive bacteria as well as Candida albicans. Antimicrobial activity was studied. Both minimal Inhibitory Concentrations (MIC) and minimal biocidal concentrations (MBC) were determined. Chitosan acetic acid recorded lower MIC values against Enterococcus faecalis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans than those exhibited by EDTA. EDTA failed to have inhibitory activity against Enterococcus faecalis as well as MBC against any of the studied microorganisms. Chitosan acetic acid's MBC were recorded to all examined species. Checkerboard assay results indicated a synergistic antimicrobial activity of the new combination against Staphylococcus aureus and an additive effect against other microorganisms. Moreover, a short microbial exposure to chitosan-EDTA (20-30 min) caused complete eradication. Due to the continuous emergence of resistant strains, there is an urgent need to discover new antimicrobial agents. Our findings suggest the use of chitosan as an enhancing agent with antibacterial and antifungal properties in combination with EDTA in pharmaceutical preparations.

Immunomodulatory effects of rosuvastatin on hepatic ischemia/reperfusion induced injury.

UNLABELLED: Liver ischemia followed by reperfusion results in liver injury which in turn produces and releases destructive proinflammatory cytokines into the circulation causing subsequent damage to other organs. This remains a significant problem for surgical procedures and liver transplantation. OBJECTIVE: In this study, we show the effect of rosuvastatin on multiple organ dysfunction induced by hepatic/ischemia reperfusion. MATERIALS AND METHODS: Hepatic ischemia and reperfusion (I/R) injury was induced in rats, and groups of rats were pretreated with oral rosuvastatin. RESULTS: Our study detected the levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), IL-10, and monocyte chemotactic protein 1 (MCP-1) not only in serum but also in liver, lung, kidney intestine, and heart tissues. Rosuvastatin pretreatment appears to protect these organs after hepatic I/R injury through the reduction of proinflammatory cytokines (TNF-α, IL-6, and MCP-1) and stimulation of anti-inflammatory cytokines (IL-10) production. DISCUSSION AND CONCLUSION: This is the first report of rosuvastatin immunomodulatory effects on multiorgan dysfunction after hepatic I/R. Our data suggest a therapeutic potential for rosuvastatin in attenuating inflammation and modulating immune response independent of lipid lowering effect.

Species distribution and antimicrobial susceptibility of gram-negative aerobic bacteria in hospitalized cancer patients.

BACKGROUND: Nosocomial infections pose significant threats to hospitalized patients, especially the immunocompromised ones, such as cancer patients. METHODS: This study examined the microbial spectrum of gram-negative bacteria in various infection sites in patients with leukemia and solid tumors. The antimicrobial resistance patterns of the isolated bacteria were studied. RESULTS: The most frequently isolated gram-negative bacteria were Klebsiella pneumonia (31.2%) followed by Escherichia coli (22.2%). We report the isolation and identification of a number of less-frequent gram negative bacteria (Chromobacterium violacum, Burkholderia cepacia, Kluyvera ascorbata, Stenotrophomonas maltophilia, Yersinia pseudotuberculosis, and Salmonella arizona). Most of the gram-negative isolates from Respiratory Tract Infections (RTI), Gastro-intestinal Tract Infections (GITI), Urinary Tract Infections (UTI), and Bloodstream Infections (BSI) were obtained from leukemic patients. All gram-negative isolates from Skin Infections (SI) were obtained from solid-tumor patients. In both leukemic and solid-tumor patients, gram-negative bacteria causing UTI were mainly Escherichia coli and Klebsiella pneumoniae, while gram-negative bacteria causing RTI were mainly Klebsiella pneumoniae. Escherichia coli was the main gram-negative pathogen causing BSI in solid-tumor patients and GITI in leukemic patients. Isolates of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, and Acinetobacter species were resistant to most antibiotics tested. There was significant imipenem -resistance in Acinetobacter (40.9%), Pseudomonas (40%), and Enterobacter (22.2%) species, and noticeable imipinem-resistance in Klebsiella (13.9%) and Escherichia coli (8%). CONCLUSION: This is the first study to report the evolution of imipenem-resistant gram-negative strains in Egypt. Mortality rates were higher in cancer patients with nosocomial Pseudomonas infections than any other bacterial infections. Policies restricting antibiotic consumption should be implemented to avoid the evolution of newer generations of antibiotic resistant-pathogens.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) colonization and infection in intravenous and inhalational opiate drug abusers.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in hospital-acquired and community-acquired infections. We hypothesized that drug abuse is a risk factor for community-acquired MRSA (CA-MRSA) infection, and we employed a rapid multiplex PCR technique for MRSA identification. The study was conducted on MRSA isolates from 60 opiate addicts (intravenous and inhalational drug users) to detect the rate and location of MRSA colonization and infection among them in comparison to 60 non-addict patients and 15 healthy volunteer controls. The proportion of addicts with MRSA colonization (and/or infection) was significantly higher than non-addict patients with MRSA colonization. MRSA colonization was associated with infection in 58% of MRSA-colonized addicts. The MRSA nasal carriage in the addicts was significantly higher than MRSA carriage elsewhere, whether in the addicts group or in the non-addict patients group. Moreover, the nasopharyngeal carriage rate of MRSA among addicts was significantly higher than among the non-addict patients. Increasing the duration of addiction resulted in a significant increase in CA-MRSA colonization in opiate addicts. Both inhalational and intravenous drug use led to significant MRSA colonization in the addict population. In conclusion, this study demonstrated how drug abusers, a high-risk group for infections with MRSA, could be a source or a reservoir of CA-MRSA infection in the non-addict population.

Microbial spectrum and antibiotic susceptibility profile of gram-positive aerobic bacteria isolated from cancer patients.

PURPOSE: Cancer patients are particularly susceptible to nosocomial infections because of their compromised immune system, and because of the nature of treatment practices they experience. Recently, a shift of the microbial spectrum of cancer patients from gram-negative to gram-positive has been demonstrated. This study analyzed the distribution and the antimicrobial resistance of gram-positive bacteria isolated from cancer patients in Egypt. PATIENTS AND METHODS: We examined the microbial spectrum of gram-positive bacteria in patients with hematologic malignancies and solid tumors. In addition, we also studied the antimicrobial resistance of pathogens accounting for the majority of gram-positive infections in these cancer patients. RESULTS: Most of gram-positive isolates from urinary tract (100%), respiratory tract (89.7%), and bloodstream infections (BSIs; 65.5%) were obtained from leukemic patients. All gram-positive isolates from skin infections were isolated from solid-tumor patients. In both leukemic and solid-tumor patients, gram-positive bacteria causing nosocomial BSI were mainly Coagulase-negative staphylococcus (CNS) and S. aureus, whereas gram-positive bacteria causing nosocomial RTI were mainly alpha-hemolytic streptococci and CNS. Gram-positive bacteria were not isolated from GI tract infections. S. aureus, CNS, and alpha-hemolytic streptococci demonstrated methicillin resistance (81.5%, 92.3%, and 90% resistance, respectively). S. aureus and CNS were susceptible to linezolid (15.4% and 0% resistance, respectively), and vancomycin (15.5% and 11% resistance, respectively). CONCLUSION: This is the first study to report the emergence of vancomycin- and linezolid-resistant S. aureus in Egypt. Newer generation quinolones (moxifloxacin and gatifloxacin) were more active than older quinolones (ciprofloxacin and ofloxacin) against S. aureus and CNS, suggesting the use of newer generation quinolones in the prophylaxis of cancer patients.