Comparison of different colistin regimens for the treatment of pneumonia caused by multidrug-resistant microorganisms: a systematic review and meta-analysis.

OBJECTIVE: Multidrug-resistant pneumonia is a common cause of hospital-related morbidity and mortality across the world. The high prevalence of multidrug-resistant pneumonia due to resistant gram-negative pathogens has led to a re-introduction of colistin. The adverse events associated with intravenous colistin can be alleviated by administering the drug nasally (i.e., inhalation) or in a combination including both inhalation and intravenous presentations of the drug. A review study compared the impact of these administration methods on clinical, morbidity, and mortality-related outcomes in patients with multiple-drug resistant pneumonia. However, the publication of newer cohort trials, warrants an update of the state of the evidence. To compare the clinical, morbidity, and mortality outcomes in patients with multidrug-resistant pneumonia receiving either intravenous colistin or combined drug presentations (ie, inhaled and intravenous). MATERIALS AND METHODS:  A systematic search of the academic literature was performed according to the PRISMA guidelines across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE). We conducted a random-effect meta-analysis to compare outcomes such as rate of clinical cure, microbiological eradication, nephrotoxicity, and overall mortality in patients with multidrug-resistant pneumonia receiving either intravenous colistin, inhaled colistin, or a combination of those administration routes. RESULTS:  From 963 studies, we found 16 eligible studies with 1651 patients (61.6 ± 7.7 years) with multidrug-resistant pneumonia who had received either intravenous, inhaled colistin or a combined inhaled/intravenous administration. Our meta-analysis revealed higher rates of clinical cure (OR, 1.61) and microbiological eradication (1.37) in patients receiving combined intravenous/inhaled colistin than in those receiving intravenous colistin alone. Additional analyses revealed higher rates of nephrotoxicity (1.30) and mortality (1.44) in patients receiving intravenous colistin than in those receiving combined intravenous/inhaled colistin. CONCLUSIONS:  We provide evidence showing improved clinical, morbidity, and mortality outcomes in patients with multidrug-resistant pneumonia receiving inhaled colistin or combined inhaled/intravenous colistin than those receiving intravenous colistin alone. These findings should help clinicians stratify the risks associated with different colistin administration routes to manage multidrug-resistant pneumonia.

Ultrastructural and Cytochemical Properties of Peripheral Blood Cells of Piebald Naked Carp (Gymnocypris eckloni).

The ultrastructural and cytochemical properties of peripheral blood cells of Gymnocypris eckloni were investigated by transmission electron microscopy and a range of cytochemical techniques to provide clear insight into the structure and function of blood cells from this fish. Ultrastructurally, erythrocytes, leucocytes (neutrophils, eosinophils, lymphocytes, monocytes), thrombocytes and plasma cells were identified in the peripheral blood of G. eckloni. The most special ultrastructural characteristics of blood cells in this fish were that neutrophils exhibited only one type of cytoplasmic granules containing an eccentric, spherical or oval electron-dense core, and eosinophils presented two types of granules with non-uniform electronic density and without crystalloids in their cytoplasm. Neutrophils, eosinophils, lymphocytes, monocytes and thrombocytes were positive for periodic acid-Schiff and α-naphthyl acetate esterase staining. Intense peroxidase positive staining was observed in neutrophils and monocytes, but not in eosinophils, lymphocytes and thrombocytes. Neutrophils, eosinophils and monocytes were stained positively for acid phosphatase, whereas lymphocytes and thrombocytes did not stain. Leucocytes and thrombocytes were negative for alkaline phosphatase and Sudan black B staining. Erythrocytes were negative for all cytochemical staining. The cytochemical and ultrastructural features of peripheral blood cells of G. eckloni were similar to those of other fish species. However, some important differences were identified in G. eckloni.

Effect of the Fusarium toxins, zearalenone and deoxynivalenol, on the mouse brain.

The aim of this study was to find effects of Fusarium toxins on brain injury in mice. We evaluated the individual and combined effect of the Fusarium toxins zearalenone and deoxynivalenol on the mouse brain. We examined brain weight, protein, antioxidant indicators, and apoptosis. After 3 and 5days of treatment, increased levels of nitric oxide, total nitric oxide synthase, hydroxyl radical scavenging, and malondialdehyde were observed in the treatment groups. This was accompanied by reduced levels of brain protein, superoxide dismutase (apart from the low-dose zearalenone groups), glutathione, glutathione peroxidase activity, and percentage of apoptotic cells. By day 12, most of these indicators had returned to control group levels. The effects of zearalenone and deoxynivalenol were dose-dependent, and were synergistic in combination. Our results suggest that brain function is affected by zearalenone and deoxynivalenol.

Effects of local radiofrequency denervation on ventricular electrophysiological properties in normal and acute myocardial ischemia heart.

OBJECTIVE: To observe the effects of local radiofrequency denervation on ventricular effective refractory periods, electrical alternans and ventricular arrhythmia susceptibility post myocardial infarction. MATERIALS AND METHODS: Thirty-four mongrel dogs were randomly divided into the normal heart group (n = 16, 8 in sham and 8 in local sympathetic denervation - LSD) and the acute myocardial ischemia (AMI) group (n = 18, 9 in control and 9 in LSD). The left cardiac sympathetic nerve was denervated with irrigated catheter radiofrequency ablation. Left ventricular effective refractory periods (ERP), monophasic action potential duration at 90% (APD90) and APD alternans were measured at baseline and 2 hours after LSD in the normal heart group. AMI was induced by ligating the left anterior descending coronary artery 2 hours after LSD was performed. Then APD90, the occurrence of ventricular arrhythmias (VAs) were measured. RESULTS: Compared with baseline, LSD significantly prolonged ventricular ERP and APD90 at all sites (p < 0.05 for all) in the LSD group, whereas no significant change was shown in the sham group. But their spatial dispersions did not change in both groups. APD alternans occurred at shorter pacing cycle length at each site after LAD→LSD when compared to the sham group (p < 0.05 for all). After AMI, the occurrence of VAs was significantly lower in the LSD group than in the control group (p < 0.05). CONCLUSIONS: LSD may have a beneficial impact on ventricular arrhythmias induced by AMI through modulation of autonomic tone.

The Fusarium toxin zearalenone and deoxynivalenol affect murine splenic antioxidant functions, interferon levels, and T-cell subsets.

This study aimed to evaluate the effects of the Fusarium toxin zearalenone (ZEA) and deoxynivalenol (DON) on splenic antioxidant functions, IFN levels, and T-cell subsets in mice. Herein, 360 mice were assigned to nine groups for a 12-day study. Mice were administered an intraperitoneal injection for 4 consecutive days with different concentrations of ZEA alone, DON alone, or ZEA+DON. Spleen and blood samples were collected on days 0, 3, 5, 8, and 12. Mice in each of the experimental groups showed dysreglated splenic antioxidant functions, IFN levels, and T-cell subset frequencies, suggesting that the immune system had been affected. The ZEA+DON-treated groups, especially the group that received a higher concentration of ZEA+DON (Group D2Z2), showed more obvious effects on the dysregulation of splenic antioxidant functions, IFN levels, and T-cell subsets. This finding suggested that DON and ZEA exerted synergistic effects.

Morphological and cytochemical studies of peripheral blood cells of Schizothorax prenanti.

The morphological and cytochemical studies of peripheral blood cells of Schizothorax prenanti were studied by light and electron microscopy. Erythrocytes, thrombocytes and three types of leucocytes, lymphocytes, neutrophils and monocytes, were distinguished and characterized. In addition to mature erythrocytes, immature and dividing erythrocytes were observed. A few organelles such as mitochondria were distributed in the cytoplasm of erythrocytes. Lymphocytes with heavily clumped heterochromatic nucleus and minimal cytoplasm were classified into small and large lymphocytes. Three different populations of granules, with distinctive ultrastructural aspect, were observed in neutrophils. Monocytes were the fewest leucocytes possessing rich organelles, phagocytized materials and vacuoles. Thrombocytes with various types were the most abundant blood cells among leucocytes and contained a prominent nucleus with dense bands of heterochromatin and many cytoplasmic vacuoles. Periodic acid-Schiff staining was positive in neutrophils, monocytes, lymphocytes and thrombocytes, but not in erythrocytes. Peroxidase-positive staining was observed in neutrophils and monocytes, but not in erythrocytes, lymphocytes and thrombocytes. Only neutrophils were positive for oil red O. Except for erythrocytes, the other blood cells stained positively for acid phosphatase. Only neutrophils and monocytes were positive for α-naphthyl acetate esterase. None of the cells studied were positive for alkaline phosphatase. The morphologic and cytochemical features of blood cells of S. prenanti are similar to those of other fish. This investigation may be helpful as a tool to monitor the health status of cultured S. prenanti and will grant early detection of clinical pathology.

Effects of zearalenone on calcium homeostasis of splenic lymphocytes of chickens in vitro.

Zearalenone (ZEA) is an estrogenic mycotoxin. It is produced by several Fusarium species and can contaminate food and feed. To investigate the role of calcium homeostasis in ZEA-induced toxicity of poultry and elucidate its cytotoxic mechanism, splenic lymphocytes isolated from chickens were exposed to ZEA (0-25 µg/mL) for 48 h. The intracellular calcium concentration ([Ca2+]i), pH, calmodulin (CaM) mRNA levels, and Na+/K+-ATPase activities and Ca2+-ATPase activities were detected by the fluorescent dyes Fluo-3/AM and BCECF/AM, quantitative real-time PCR, and chromatometry. Supernatant CaM concentrations were simultaneously detected by ELISA. As the ZEA exposure concentration increased, the [Ca2+]i and CaM mRNA levels gradually increased, while intracellular pH, CaM concentrations of supernatants, and intracellular Na+,K+-ATPase and Ca2+-ATPase activities gradually decreased in a dose-dependent manner. There were significant differences (P<0.05 or P<0.01) between the treatment groups and the control group. These results indicate that ZEA cytotoxicity arises by causing an imbalance in calcium homeostasis and intracellular acidification in lymphocytes.

Effects of zearalenone on IL-2, IL-6, and IFN-γ mRNA levels in the splenic lymphocytes of chickens.

Zearalenone (ZEN) is an estrogenic mycotoxin produced by several Fusarium species, which can contaminate food and feed. These compounds elicit a wide spectrum of toxic effects, including the capacity to alter normal immune function. In this study, the in vitro effects of the treatment of ConA-stimulated splenic lymphocytes with ZEN (0-25 µg/mL) were examined. ZEN modulates the expression of IL-2, IL-6, and IFN-γ. The IL-2 levels were up to fourfold higher (P < 0.05) compared with the levels in the control at toxin concentrations of 25 µg/mL after 48 h of treatment. The IL-6 levels were critically suppressed at this concentration; these changes were very statistically significant (P < 0.05). At lower ZEN concentrations (0.1, 0.4 and 1.6 µg/mL), the IFN-γ levels changed slightly; however at 6.25 and 25 µg/mL, the IFN-γ results reached statistical significance compared with the control levels (P < 0.05). These data suggest that ZEN has potent effects on the expression of chicken splenic lymphocytes cytokines at the mRNA level.

Histopathology, immunohistochemistry, in situ apoptosis, and ultrastructure characterization of the digestive and lymphoid organs of new type gosling viral enteritis virus experimentally infected gosling.

Here, for the first time, to colocalize new type gosling viral enteritis virus (NGVEV) with histological lesions and in situ apoptosis in the digestive organs (esophagus, proventriculus, gizzard, small intestine, cecum, rectum, liver, and pancreas) and the lymphoid organs (bursa of Fabricius, thymus, Harderian gland, and spleen) of experimentally infected goslings, portions of tissues were collected at sequential infection time points and examined by histopathology for histological lesions, immunohistochemical staining for viral antigens, ultrastructural observation by transmission electron microscope (TEM) for virus particles and apoptotic cells, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay for in situ apoptosis. The hyperemia, hemorrhage, infiltration of lymphocytes, progressive lymphoid depletion, apoptosis, and necrosis were readily observed in the lymphoid organs and intestine tract by histopathological examination. The NGVEV particles and viral antigens widely appeared in the small intestine and bursa of Fabricius as early as 2 d postinfection (PI) by TEM and immunohistochemical staining, and the presence and quantity of it reached a maximum during 6 to 12 d PI. The principal sites for NGVEV were endothelial cells, epithelia, mucosal cells, glandular cells, fibrocytes, macrophages, and lymphocytes. A series of apoptotic morphological changes including chromatin condensation and margination, cytoplasmic shrinkage, and formation of apoptotic body were observed by TEM, and the number of apoptotic cells was largely increased from 4 d PI and peaked at 9 d PI by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling analysis. The histological organ lesions and apoptosis in vivo were generally associated with sites of NGVEV localization, which can be regarded as the cause of death. This work may shed light on the pathogenesis of new type gosling viral enteritis and put new insight into the pathogenesis of goose adenovirus.

The H19 transcript is associated with polysomes and may regulate IGF2 expression in trans.

The imprinted H19 gene produces a fully processed transcript that does not exhibit any conserved open reading frame between mouse and man. Although transcriptional control elements associated with the mouse H19 locus have been shown to control the neighboring Igf2 gene in cis, the prevailing view is that the cytoplasmic H19 transcript does not display any function. In contrast to earlier reports, we show here that the H19 transcript is associated with polysomes in a variety of cell types, in both mouse and man. A possible trans-function of the H19 gene is suggested by a reciprocal correlation in trans between cytoplasmic H19 and IGF2 mRNA levels, as well as IGF2 mRNA translatability. We discuss these results in terms of their challenge to the prevailing dogma on the function of the enigmatic H19 gene, as well as with respect to the ontogeny of the Beckwith-Wiedemann syndrome, and propose that the human H19 gene is an antagonist of IGF2 expressivity in trans.