Gut-Kidney Impairment Process of Adenine Combined with Folium sennae-Induced Diarrhea: Association with Interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and Acetic Acid, Inflammation, and Kidney Function.

BACKGROUND: Extensive evidence suggests that gut microbiota may interact with the kidneys and play central roles in the pathogenesis of disease. However, the association of gut microbiota-kidneys in diarrhea remains unclear. METHODS: A diarrhea mouse model was constructed by combining adenine with Folium sennae. We analyzed the characteristics of the gut content microbiota and short chain fatty acids (SCFAs); and explored the potential link between gut content microbiota, SCFAs, intestinal inflammatory response and kidney function. RESULTS: Characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens were enriched in the gut contents of mice. The productions of SCFAs were remarkably inhibited. Model mice presented an increased trend of creatinine (Cr), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), a decreased trend of blood urea nitrogen (BUN) and secretory immunoglobulin A (SIgA). The pathological analysis proved obvious damage to the kidney structure. Lactobacillus intestinalis and Bacteroides acidifaciens exisited in the correlations with acetic acid, intestinal inflammatory response and kidney function. CONCLUSIONS: Adenine combined with Folium sennae-induced diarrhea, altered the structure and function of the gut content microbiota in mice, causing the enrichment of the characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens. The interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and acetic acid, intestinal inflammation, and kidney function might be involved in the process of gut-kidney impairment in adenine, combined with Folium sennae-induced diarrhea.

Lumpfish (Cyclopterus lumpus) Is Susceptible to Renibacterium salmoninarum Infection and Induces Cell-Mediated Immunity in the Chronic Stage.

Renibacterium salmoninarum is a Gram-positive, intracellular pathogen that causes Bacterial Kidney Disease (BKD) in several fish species in freshwater and seawater. Lumpfish (Cyclopterus lumpus) is utilized as a cleaner fish to biocontrol sea lice infestation in Atlantic salmon (Salmo salar) farms. Atlantic salmon is susceptible to R. salmoninarum, and it can transfer the infection to other fish species. Although BKD outbreaks have not been reported in lumpfish, its susceptibility and immune response to R. salmoninarum is unknown. In this study, we evaluated the susceptibility and immune response of lumpfish to R. salmoninarum infection. Groups of lumpfish were intraperitoneally (i.p.) injected with either R. salmoninarum (1×107, 1×108, or 1×109 cells dose-1) or PBS (control). R. salmoninarum infection kinetics and mortality were followed for 98 days post-infection (dpi). Transcript expression levels of 33 immune-relevant genes were measured in head kidney (n = 6) of fish infected with 1×109 cells/dose and compared to the control at 28 and 98 dpi. Infected lumpfish displayed characteristic clinical signs of BKD. Lumpfish infected with high, medium, and low doses had a survival rate of 65%, 93%, and 95%, respectively. Mortality in the high-dose infected group stabilized after 50 dpi, but R. salmoninarum persisted in the fish tissues until 98 dpi. Cytokines (il1ß, il8a, il8b), pattern recognition receptors (tlr5a), interferon-induced effectors (rsad2, mxa, mxb, mxc), and iron regulation (hamp) and acute phase reactant (saa5) related genes were up-regulated at 28 dpi. In contrast, cell-mediated adaptive immunity-related genes (cd4a, cd4b, ly6g6f, cd8a, cd74) were down-regulated at 28 dpi, revealing the immune suppressive nature of R. salmoninarum. However, significant upregulation of cd74 at 98 dpi suggests induction of cell-mediated immune response. This study showed that R. salmoninarum infected lumpfish in a similar fashion to salmonid fish species and caused a chronic infection, enhancing cell-mediated adaptive immune response.

Using Cordyceps militaris extracellular polysaccharides to prevent Pb2+-induced liver and kidney toxicity by activating Nrf2 signals and modulating gut microbiota.

In this study, we investigated the protective efficacy of extracellular polysaccharide from Cordyceps militaris (CEP-I) in liver and kidney and their regulating effect on gut microbiota against Pb-induced toxicity in vivo. The results indicated that CEP-I could reduce the Pb2+ content and organ index of liver and kidney in mice. Besides, biochemical analysis showed that CEP-I could improve the activity of glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and superoxide dismutase (SOD) in serum and organs, restore the physiological indexes of total protein (TP), albumin (ALB), blood urea nitrogen (BUN) and creatinine (CRE) in serum and decrease the enzyme activity of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) in the liver and kidney of mice poisoned by Pb2+. This indicated that CEP-I has a protective effect on organs against damage in mice. In addition, CEP-I could regulate the expression of key proteins in the Nrf2 signaling pathway, including NF-E2-related factor 2 (Nrf2), Kelch-like ECH-associated protein-1 (Keap1), Heme oxygenase (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1). Furthermore, the intestinal flora analysis results indicated that CEP-I also has the capacity to regulate the intestinal flora imbalance caused by Pb2+ in poisoned mice. In conclusion, we hope that this study can provide theoretical basis for the treatment of tissue damage induced by Pb2+.

Fecal metabonomics combined with 16S rRNA gene sequencing to analyze the changes of gut microbiota in rats with kidney-yang deficiency syndrome and the intervention effect of You-gui pill.

ETHNOPHARMACOLOGICAL RELEVANCE: A myriad of evidence have shown that kidney-yang deficiency syndrome (KYDS) is associated with metabolic disorders of the intestinal microbiota, while TCMs can treat KYDS by regulating gut microbiota metabolism. However, the specific interplay between KYDS and intestinal microbiota, and the intrinsic regulation mechanism of You-gui pill (YGP) on KYDS' gut microbiota remains largely unknown so far. MATERIALS AND METHODS: In the present study, fecal metabonomics combined with 16S rRNA gene sequencing analysis were used to explore the mutual effect between KYDS and intestinal flora, and the intrinsic regulation mechanism of YGP on KYDS's gut microbiota. Rats' feces from control (CON) group, KYDS group and YGP group were collected, and metabolomic analysis was performed using 1H NMR technique combined with multivariate statistical analysis to obtain differential metabolites. Simultaneously, 16S rRNA gene sequencing analysis based on the Illumina HiSeq sequencing platform and ANOVA analysis were used to analyze the composition of the intestinal microbiota in the stool samples and to screen for the significant altered microbiota at the genus level. After that, MetaboAnalyst database and PICRUSt software were apply to conduct metabolic pathway analysis and functional prediction analysis of the screened differential metabolites and intestinal microbiota, respectively. What's more, Pearson correlation analysis was performed on these differential metabolites and gut microbiota. RESULTS: Using fecal metabonomics, KYDS was found to be associated with 21 differential metabolites and seven potential metabolic pathways. These metabolites and metabolic pathways were mainly involved in amino acid metabolism, energy metabolism, methylamine metabolism, bile acid metabolism and urea cycle, and short-chain fatty acid metabolism. Through 16S rRNA gene sequencing analysis, we found that KYDS was related to eleven different intestinal microbiotas. These gut microbiota were mostly involved in amino acid metabolism, energy metabolism, nervous, endocrine, immune and digestive system, lipid metabolism, and carbohydrate metabolism. Combined fecal metabonomics and 16S rRNA gene sequencing analysis, we further discovered that KYDS was primarily linked to three gut microbiotas (i.e. Bacteroides, Desulfovibrio and [Eubacterium]_coprostanoligenes_group) and eleven related metabolites (i.e. deoxycholate, n-butyrate, valine, isoleucine, acetate, taurine, glycine, α-gluconse, ß-glucose, glycerol and tryptophan) mediated various metabolic disorders (amino acid metabolism, energy metabolism, especially methylamine metabolism, bile acid metabolism and urea cycle, short-chain fatty acid metabolism. nervous, endocrine, immune and digestive system, lipid metabolism, and carbohydrate metabolism). YGP, however, had the ability to mediate four kinds of microbes (i.e. Ruminiclostridium_9, Ruminococcaceae_UCG-007, Ruminococcaceae_UCG-010, and uncultured_bacterium_f_Bacteroidales_S24-7_group) and ten related metabolites (i.e. deoxycholate, valine, isoleucine, alanine, citrulline, acetate, DMA, TMA, phenylalanine and tryptophan) mediated amino acid metabolism, especially methylamine metabolism, bile acid metabolism and urea cycle, short-chain fatty acid metabolism, endocrine, immune and digestive system, and lipid metabolism, thereby exerting a therapeutic effect on KYDS rats. CONCLUSION: Overall, our findings have preliminary confirmed that KYDS is closely related to metabolic and microbial dysbiosis, whereas YGP can improve the metabolic disorder of KYDS by acting on intestinal microbiota. Meanwhile, this will lay the foundation for the further KYDS's metagenomic research and the use of intestinal microbiotas as drug targets to treat KYDS.

Intestinal Microbiota and Kidney Diseases.

Kidney diseases are common and the incidence rate is increasing. Gut microbiota is involved in metabolic and immune regulation of the host. Genetic, alimentary and environmental disease factors may change gut flora and increase opportunistic and pathogenic bacteria, contributing to immune or non-immune mediated kidney diseases including IgA nephropathy and diabetic nephropathy. Additionally, bacterial metabolites may be a source of uremic toxins. Thus, identification of diversity, composition, and metabolic and immunologic features of gut bacteria in chronic kidney diseases may help understand pathogenetic mechanism and develop therapy for diseases.

Aqueous extract from Orthosiphon stamineus leaves prevents bladder and kidney infection in mice.

BACKGROUND: Extracts from the leaves of Orthosiphon stamineus are used in phytotherapy for treatment of uncomplicated urinary tract infections. PURPOSES: Evaluation of an aqueous extract against infection with uropathogenic Escherichia coli in vivo; investigation of underlying microbiological mechanisms. STUDY DESIGN: In vivo studies in mice and in vitro investigations on cytotoxicity, antiadhesive potential, influence on bacterial gene expression and quorum sensing. METHODS: Extract OWE was prepared by hot water extraction. For in vivo studies BALB/c mice were used in an UPEC infection model. The effect of OWE on bacterial load in bladder/kidney tissue was monitored in pre- and posttreatment. Cytotoxicity of OWE against different UPEC strains, T24 bladder/A498 kidney cells, gene expression analysis, monitoring of phenotypic motility and quorum sensing was investigated by standard methods of microbiology. RESULTS: OWE was quantified (UHPLC) according to the content of rosmarinic acid, cichoric acid, caffeic acid. Three- and 5-day treatment of animals with OWE (750mg/kg) after transurethral infection with UPEC CFT073 reduced the bacterial load in bladder and kidney, similar to norfloxacin. Four- and 7-day pretreatment of mice prior to the infection with UPEC NU14 reduced bacterial bladder colonization. In vitro investigations indicated that OWE (≤2mg/ml) has no cytotoxic or proliferation-inhibiting activity against different UPEC strains as well as against T24 bladder and A498 kidney cells. OWE exerts a dose dependent antiadhesive activity against UPEC strains NU14 and UTI89. OWE reduced gene expression of fimH, but evoked increase of the expression of motility/fitness gene fliC. Increase of bacterial motility on gene level was confirmed by a changed bacterial phenotype by an increased bacterial motility in soft agar assay. OWE inhibited in a concentration-dependent manner bacterial quorum sensing. CONCLUSION: OWE is assessed as a strong antiadhesive plant extract for which the traditional use in phytotherapy for UTI might be justified.

Analysis of daptomycin efficacy and breakpoint standards in a murine model of Enterococcus faecalis and Enterococcus faecium renal infection.

Daptomycin efficacy against clinical isolates of Enterococcus faecalis, Enterococcus faecium, and a lab-derived daptomycin-resistant isolate of E. faecalis was investigated in a mouse model of renal infection. The daptomycin MICs against these enterococci ranged from 0.5 to 50 micro g/ml. The objective of this study was to determine the relationship between the MICs of drugs against E. faecalis and E. faecium and the level of daptomycin exposure needed to evaluate the drug's efficacy. Correlating the required therapeutic exposures of mice with the exposures achieved clinically allowed us to project enterococcal breakpoint values. Mice pretreated with carrageenan were infected intravenously with 3 x 10(8) to 4 x 10(8) CFU of E. faecalis or E. faecium. Daptomycin (5 to 50 mg of drug/kg of body weight) or saline control was administered 4 h postinfection and continued once daily for 2 days (three total doses). On day 4, infected kidneys were harvested, homogenized, and dilution plated. Efficacy was defined as a > or = 2-log(10) (99%) reduction in bacterial burden in infected kidneys. At clinically relevant dosages and exposures (area under the curve, 400 to 600 microg.hr/ml), daptomycin demonstrated similar and marked efficacy against all clinical enterococcal isolates tested. Daptomycin achieved efficacy with comparable doses against both vancomycin-sensitive (MIC, < or = 4 microg/ml) and -resistant enterococcal strains tested. Efficacy was also established against the lab-derived daptomycin-resistant E. faecalis isolate. In this murine renal infection model, clinically relevant exposures of daptomycin were effective against E. faecalis and E. faecium strains for which MICs were < or = 8 microg/ml. These murine efficacy data for daptomycin, along with surveillance data and human pharmacokinetic exposures achieved, suggest a breakpoint concentration value of < or = 8 microg/ml (susceptible) and > or = 16 microg/ml (resistant) for daptomycin against E. faecium and E. faecalis.

Colony morphology switching of Candida lusitaniae and acquisition of multidrug resistance during treatment of a renal infection in a newborn: case report and review of the literature.

Candida lusitaniae is an emerging opportunistic pathogen which exhibits an unusual antifungal susceptibility pattern. We describe a case of fatal renal infection due to C. lusitaniae in a very low birth weight neonate who was treated with short courses of fluconazole given alternately with amphotericin B. A colony morphology switching was detected on the standard primary culture medium by changes in colony size. Switching was shown to affect deeply the susceptibility to amphotericin B. Afterwards, the switched phenotype developed a cross resistance to fluconazole and itraconazole. Several issues raised by this case are discussed in the light of an extensive review of the literature. Our observations point out the importance of both the detection of colony morphology switching and the close monitoring of antifungal susceptibility in the management of infections due to C. lusitaniae. A judicious therapeutic strategy should prevent the acquisition of multidrug resistance during antifungal therapy.

Comparative therapeutic efficacy of clinafloxacin in a Pseudomonas aeruginosa mouse renal abscess model.

A deep-seated Pseudomonas aeruginosa mouse kidney abscess model was used to compare the therapeutic efficacy of clinafloxacin, a fluoroquinolone in clinical trials, with that of clinically relevant standard drugs. Following 50 mg/kg oral doses, twice daily for five consecutive days, clinafloxacin produced a 4 log decrease in mean bacterial count, the greatest decrease of all drugs tested. The same dosage regimen resulted in complete bacterial eradication in 88% of the kidneys. No other compound produced total bacterial clearance in 50% of the kidneys at the highest dose tested.

[A patient with generalized actinomycosis]. / Een patiënt met een gegeneraliseerde actinomycose.

A 36-year-old man was admitted because of haemoptysis and weight loss. Despite elaborate investigations, including multiple biopsies of affected organs (pleura, lung, kidney and liver) no diagnosis was established. The patient refused further diagnostic procedures and left hospital for winti treatment in Surinam. He did not take the prescribed pheneticillin and returned after seven weeks in a very poor condition. The second admission was complicated by septic shock. Despite intensive treatment he died. On autopsy actinomycosis abscesses were found in lung, liver and kidney. Even when suspected, an infection with Actinomyces is difficult to diagnose. Without adequate treatment this infection can lead to life-threatening complications.

Growth of the fish pathogen Renibacterium salmoninarum on different media.

In the present study, the ability of a group of Renibacterium salmoninarum strains to grow in the presence or absence of the amino acid cysteine and other mineral and organic sources of sulfur and nitrogen has been evaluated. Most of the isolates tested were able to grow on a mineral media supplemented with L-cysteine-HCl or other organic compounds, such as the vitamin thiamine and a casein hydrolysate (Bacto Casamino Acids, Difco). Bacterial growth was also recorded on commercial and specific media not supplemented with L-cysteine-HCl, or in which this amino acid was replaced by the compounds cited above.

Successful treatment of extensive posttraumatic soft-tissue and renal infections due to Apophysomyces elegans.

We describe the clinical course and successful treatment of a previously healthy man who, after experiencing trauma, presented with severe cutaneous mucormycosis due to Apophysomyces elegans and subsequently developed secondary renal infection. A multidisciplinary approach employing aggressive surgical debridement and therapy with hyperbaric oxygen, liposomal amphotericin B, and interferon-gamma was successful in controlling his infection, obviating the need for nephrectomy.

Antibacterial activity of sparfloxacin against experimental renal infections in mice.

In a murine model of renal infection (Staphylococcus aureus and Escherichia coli), sparfloxacin was compared with ciprofloxacin and fleroxacin. After intrarenal inoculation, mice were treated orally for 5 days. The drugs were administered at five different dosages, ranging from 3.125 to 50 mg/kg of body weight per day for S. aureus and from 0.78 to 12.5 mg/kg/day for E. coli. Evaluation of efficacy was based on the proportional reduction of bacterial counts in the kidney tissues of treated animals compared with those of untreated control animals. For S. aureus, the doses required to clear the infection in 50% of mice were as follows: sparfloxacin, 10 mg/kg/day; ciprofloxacin, 33 mg/kg/day; and fleroxacin, 16 mg/kg/day. For E. coli renal infection, the corresponding dosages were as follows: sparfloxacin, 1.5 mg/kg/day; ciprofloxacin, 2.45 mg/kg/day; and fleroxacin, 1.8 mg/kg/day. Sparfloxacin and fleroxacin have a lower effective dose than ciprofloxacin in these models, probably because ciprofloxacin has a shorter serum half-life than the other two compounds.

Gallium scan in the diagnosis and treatment of renal malacoplakia.

A middle-aged female was admitted with a presumptive diagnosis of pyelonephritis that failed to respond to conventional antibiotic therapy. Multiple investigations to define the etiology of the persistent fever and accompanying acute renal failure were negative. A gallium scan revealed intense uptake in the renal parenchyma. Percutaneous renal biopsy revealed malacoplakia. Six weeks of therapy with ciprofloxacin resulted in resolution of fever, improvement in the follow-up gallium scan, and reversal of the acute renal failure.

[A rapid test of urine microflora sensitivity to antibacterial drugs in the treatment of children with nonspecific inflammatory diseases of the kidney and urinary tract]. / Uskorennoe opredelenie chuvstvitel'nosti mikroflory mochi k antibakterial'nym preparatam v lechenii detei s nespetsificheskimi vospalitel'nymi zabolevaniiami pochek i mochevyvodiashchikh putei.

The authors describe their own method for rapid determination of urine microflora sensitivity to antibacterial drugs. The method is based on the capacity of the microorganisms (as a totality of particles with the refractive index different from that of the medium) of increasing the optical density of the medium under the conditions of unlimited resources of the nutrition and space at the expense of reproduction in a liquid culture medium. The lack of the optical density increase in the urine sample after addition to it of a certain amount of antibacterial substances evidences the death of the population of the microorganisms and of its sensitivity to the antibacterial drug under study. The method proposed by the authors was compared to those widely used in clinical practice. With special reference to a concrete patient, the results obtained with the authors' method turned out to correlate with those derived with the use of the conventional methods for urine microflora sensitivity to antibacterial drugs (the disc method and the triphenyltetrazolium chloride test). That the final result of the investigation can be obtained after 2--6 hours and low labour intensivity of the method permit the institution of adequate antibiotic therapy within the first day since the patient's admission to the hospital.

Sensitivity of cytomegalovirus to intravenous foscarnet treatment.

Intravenous foscarnet was given on an emergency basis to 30 immunosuppressed patients with cytomegalovirus (CMV) disease, of whom 28 were organ transplant recipients. Thirteen patients responded to foscarnet by cessation of CMV secretion. The in vitro sensitivity to foscarnet of the CMV isolates from non-responders before, during and after foscarnet treatment was similar to that of viral isolates from responders before or during foscarnet treatment and also to CMV isolates from non-treated patients, with mean in vitro IC50 values of 239-294 microM of foscarnet. Thus, there was no evidence of increased resistance of the CMV isolates obtained after foscarnet treatment. A higher total foscarnet dose appeared to favor response.

Ciprofloxacin in experimental aortic valve endocarditis due to Pseudomonas aeruginosa.

Left-sided endocarditis caused by Pseudomonas aeruginosa is frequently associated with failure of medical therapy in man. The efficacy of ciprofloxacin and netilmicin + azlocillin has been studied in 79 rabbits with aortic valve endocarditis caused by a serum-resistant strain of P. aeruginosa. Infected animals received either: no therapy; ciprofloxacin (80 mg/kg/day); or netilmicin (6.5 mg/kg/day) + azlocillin (400 mg/kg/day). Ciprofloxacin significantly lowered vegetation titers of P. aeruginosa at days 6 and 10 of therapy compared with netilmicin + azlocillin (P less than 0.001). Similarly, ciprofloxacin was significantly more effective in sterilizing vegetations (P less than 0.005), curing P. aeruginosa endocarditis (P less than 0.001), and preventing bacteriological relapse after discontinuing antibiotic therapy (P less than 0.005). Both antibiotic regimens were equally effective in sterilizing renal abscesses. Resistance to azlocillin was occasionally observed in vivo among P. aeruginosa isolates within cardiac vegetations during the second week of therapy, but not to ciprofloxacin or netilmicin.