Synergistic depletion of gut microbial consortia, but not individual antibiotics, reduces amyloidosis in APPPS1-21 Alzheimer's transgenic mice.

In preceding efforts, we demonstrated that antibiotic (ABX) cocktail-mediated perturbations of the gut microbiome in two independent transgenic lines, termed APPSWE/PS1ΔE9 and APPPS1-21, leads to a reduction in Aß deposition in male mice. To determine whether these observed reductions of cerebral Aß amyloidosis are specific to any individual antibiotic or require the synergistic effects of several antibiotics, we treated male APPPS1-21 transgenic mice with either individual ABX or an ABX cocktail and assessed amyloid deposition. Specifically, mice were subject to oral gavage with high dose kanamycin, gentamicin, colistin, metronidazole, vancomycin, individually or in a combination (ABX cocktail) from postnatal days (PND) 14 to 21, followed by ad libitum, low-dose individual ABX or ABX cocktail in the drinking water until the time of sacrifice. A control group was subject to gavage with water from PND 14 to 21 and received drinking water till the time of sacrifice. At the time of sacrifice, all groups showed distinct cecal microbiota profiles with the highest differences between control and ABX cocktail-treated animals. Surprisingly, only the ABX cocktail significantly reduced brain Aß amyloidosis compared to vehicle-treated animals. In parallel studies, and to assess the potential exposure of ABX to the brain, we quantified the levels of each ABX in the brain by liquid chromatography-mass spectrometry (LC-MS) at PND 22 or at 7 weeks of age. With the exception of metronidazole (which was observed at less than 3% relative to the spiked control brains), we were unable to detect the other individual ABX in brain homogenates. Our findings suggest that synergistic alterations of gut microbial consortia, rather than individual antimicrobial agents, underlie the observed reductions in brain amyloidosis.

Amyloidosis secondary to chronic pulmonary aspergillosis: Case report and a systematic review of literature.

Secondary amyloidosis results from the deposition of abnormally folded proteins in body organs due to chronic inflammatory disorders. Kidneys are the most commonly affected organ and manifest as nephrotic syndrome with or without renal failure. Chronic pulmonary aspergillosis (CPA) is a chronic infection of lung parenchyma affecting those with an underlying structural lung disease. Herein, we present a case of CPA where the initial manifestation was that of nephrotic syndrome due to renal amyloidosis. We also perform a systematic review for studies describing secondary amyloidosis due to CPA.

Specific changes in faecal microbiota are associated with familial Mediterranean fever.

OBJECTIVES: Familial Mediterranean fever (FMF) can be complicated by AA amyloidosis (AAA), though it remains unclear why only some patients develop amyloidosis. We examined the gut microbiota composition and inflammatory markers in patients with FMF complicated or not by AAA. METHODS: We analysed the gut microbiota of 34 patients with FMF without AAA, 7 patients with FMF with AAA, 19 patients with AAA of another origin, and 26 controls using 16S ribosomal RNA gene sequencing with the Illumina MiSeq platform. Associations between bacterial taxa and clinical phenotypes were evaluated using multivariate association with linear models statistical method. Blood levels of interleukin (IL)-1ß, IL-6, tumour necrosis factor-α and adipokines were assessed by ELISA; indoleamine 2,3-dioxygenase (IDO) activity was determined by high-performance liquid chromatography. RESULTS: Compared with healthy subjects, specific changes in faecal microbiota were observed in FMF and AAA groups. Several operational taxonomic units (OTUs) were associated with FMF. Moreover, two OTUs were over-represented in FMF-related AAA compared with FMF without AAA. Additionally, higher adiponectin levels and IDO activity were observed in FMF-related AAA compared with FMF without AAA (p<0.05). CONCLUSION: The presence of specific changes in faecal microbiota in FMF and in FMF-related AAA suggests that intestinal microorganisms may play a role in the pathogenesis of these diseases. These findings may offer an opportunity to use techniques for gut microbiota manipulation.

NOVEL DERMATOPHILOSIS AND CONCURRENT AMYLOIDOSIS IN SANDERLINGS ( CALIDRIS ALBA) FROM LOUISIANA, USA.

: We observed Sanderlings ( Calidris alba) with facial growths in coastal Louisiana, US during summer of 2016. Severe lesions were associated with lethargy and lack of a flight response. We determined that the skin growth etiology was a bacterium of the genus Dermatophilus, rarely reported infecting birds. Sanderlings also exhibited severe amyloidosis.

Renal amyloidosis in leprosy, an infrequent cause of nephrotic syndrome in Europe.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae The main clinical manifestations involve the skin and the peripheral nervous system. Several types of nephropathy have been described in leprosy. One frequent form of renal involvement is amyloidosis, especially in patients with lepromatous leprosy. In these patients, end-stage renal disease is an important contributor to morbidity and mortality. Here, we present the case of a patient with nephrotic syndrome caused by secondary amyloidosis, chronic peripheral neuropathy and a history of leprosy. The patient was correctly treated in her youth, which is the best way to avoid renal pathology, but she developed a nephrotic syndrome years later.

[Amyloidosis in turkeys (Meleagris gallopavo f. domestica)--a case report]. / Amyloidose beim Truthuhn (Meleagris gallopavo f. domestica)--ein Fallbericht.

High prevalence of leg disorders in fattening meat turkey farm was observed. Four birds as well as tracheal and joint swabs were submitted to the Bavarian Health and Food Safety Authority in Oberschleissheim and to the Institute of Poultry Diseases, Faculty of Veterinary Medicine, Free University of Berlin. At the post-mortem, all birds showed an inflammation of the hock joints (intertarsal joint). The histopatholical investigations revealed a chronic inflammation of the joint and amyloid deposits in the joints in two cases as well as in different tissues (liver, spleen and kidneys) in another two cases. Using polymerase chain reaction, Ornithobacterium rhinotracheale-DNA could be detected in the examined tracheal and joint swabs. On the other hand, Mycoplasma gallisepticum- and Mycoplasma synoviae-DNA could not be detected. A causal correlation between the detected infectious agent and amyloidosis in relation to the leg disorders were discussed.

Systemic amyloidosis complicating multidrug-resistant tuberculosis in childhood.

Multidrug-resistant tuberculosis is increasingly common and is associated with long diagnostic delay and high morbidity. We present a 7-year-old child who developed steroid-resistant nephrotic syndrome while receiving treatment for tuberculosis. Renal biopsy results showed systemic amyloidosis; culture of peritoneal tissue confirmed disseminated multidrug-resistant tuberculosis.

Pathogenesis of experimental amyloid protein A amyloidosis in sore hocks-affected rabbits.

Although the experimental transmission of amyloid protein A (AA) amyloidosis with amyloid-enhancing factor has been studied intensively, its pathogenesis remains obscure. We previously found that rabbits affected with 'sore hocks' (SH) uniquely developed AA amyloidosis in response to primary inflammatory stimulation followed by the administration of bovine AA fibrils. However, it is unknown why only the rabbits with preexisting SH developed experimental AA amyloidosis. There may be hidden factors in the SH status that stimulate the mechanism of cross-species transmission of AA amyloidosis. To examine the essential factors in the development of experimental AA amyloidosis in SH-affected rabbits, we studied the etiology of SH in rabbits pathologically and bacteriologically. In addition, we developed artificial SH symptoms in normal rabbits by use of an adjuvant prepared from Staphylococcus aureus (StA) isolated from a spontaneous SH-affected rabbit, and we evaluated the incidence of AA amyloidosis in rabbits with or without experimental SH symptoms. We found that StA administration was extremely efficient at stimulating the induction of experimental AA amyloidosis, and the influence of SH was required. We found that the persistent S. aureus infection in SH facilitates the development of experimental AA amyloidosis in rabbits and that the inflammatory stimulation provided by SH acts as an additional accelerator in experimental AA amyloidosis.

Real-time PCR detection of Enterococcus faecalis associated with amyloid arthropathy.

AIMS: To develop a RT-PCR method for detection of the multilocus sequence type 82 of Enterococcus faecalis associated with amyloid arthropathy (AA) in layers. METHODS AND RESULTS: Bacteria were selected from lesions including AA in layers. The primers were designed based on the phosphate ATP binding cassette transporter (pstS) and xanthine phosphoribosyltransferase (xpt) genes and first tested against three isolates with known base pairs at the specific sites. Subsequently, 12 isolates were selected from our collection by one researcher, and RT-PCR was performed blinded. The sequence type (ST) was then confirmed by multilocus sequence analysis. Two single-nucleotide polymorphisms in the pstS and xpt genes allowed an unambiguous identification of ST82. As an alternative to DNA extraction, a boiling method for release of DNA from cells was used. CONCLUSIONS: The real-time PCR targeting ST82 enables rapid screening of Ent. faecalis cultured from suspect cases with results available after a few hours, much faster than multilocus sequence typing and pulse field gel electrophoresis. SIGNIFICANCE AND IMPACT OF THE STUDY: The new method allows a rapid screening of isolates with results available after only few hours. This RT-PCR method could be a useful tool for molecular epidemiological studies on the spread of arthropathic and amyloidogenic Ent. faecalis within and between birds more efficiently.

Clonality of Enterococcus faecalis associated with amyloid arthropathy in chickens evaluated by multilocus sequence typing (MLST).

The aim of the study was to evaluate the clonality of 21 strains of Enterococcus faecalis associated with arthritis and amyloid arthropathy by multilocus sequence typing (MLST). The strains originated from five countries. Fifteen of the 21 strains demonstrated the same sequence type, ST82, including a reference amyloid arthropathy strain from the Netherlands. Some of the demonstrated sequence types (ST36, ST59 and ST82) have also been described from human clinical samples while other types are reported for the first time. The results confirm previous observations that outbreaks of amyloid arthropathy seem to be clonally related and indicate a wide distribution of the predominant sequence type which was demonstrated in four countries in Europe and in the USA.

Strong correlation of B2-microglobulin (B2-m) with procalcitonin (PCT) in the serum of chronic hemodialysis patients: a role for infections in the dialysis-related amyloidosis?

INTRODUCTION: Infections trigger the activation of defensive cells capable to produce and release B(2)-microglobulin (B(2)-m). Procalcitonin (PCT), secreted by a wide range of human cells, included the aforementioned defensive cells, is generally considered a sensitive and specific marker of infection. In this prospective study, we examined the possibility that infections, as detected by increased levels of PCT, increase the serum levels of B(2)-m in chronic hemodialysis (CHD) patients, possibly affecting the rate of progression of dialysis-related amyloidosis (DRA). METHODS: For a period of four months, 76 CHD patients, 45 men/31 women, mean age 63 +/- 15.7 years, with no residual renal function and in HD for 46 +/- 50 months were studied bimonthly. Blood was drawn, at baseline T(0), two months T(2), and four months T(4), for measuring hematocrit (Ht), white blood cells (WBC), erythrocyte sedimentation rate (ESR), blood urea and serum creatinine, protein (albumin, globulin), C-reactive protein (CRP), and PCT kappa alpha iota B(2)-m. Any events (especially infections) in the preceding 10-day period were recorded. RESULTS: At baseline, 100% of all B(2)-m measurements were abnormal (>2.4 mg/L), 13.4% of PCT values were increased (>1.5 ng/mL), and 49.4% of CRP values exceeded the lower limit of 5 mg/L with no statistically significant differences between the results of the three periods of the study. Statistically significant, in all periods, was the linear positive correlation of B(2)-m with PCT (T[0]: p < 0.001, T[2]: p < 0.004, T[4]: p < 0.001). Also, statistically significant (p < 0.005) was the positive correlation of B(2)-m to HD vintage. CONCLUSIONS: In this study, the strong positive correlation of B(2)-m to PCT probably signifies that the (mainly subclinical) infections increase B(2)-m production in CHD patients intensifying the problem of HD-related amyloidosis.

Enterohepatic Helicobacter species isolated from the ileum, liver and colon of a baboon with pancreatic islet amyloidosis.

Microaerobic bacteria were isolated from a baboon with pancreatic islet amyloidosis and hepatitis. Phenotypic and molecular analyses identified two distinct helicobacters. Analyses of 16S rRNA demonstrated "Helicobacter macacae" in the ileum and liver, and Helicobacter cinaedi in the colon. To the best of the authors' knowledge, this is the first report describing the isolation of enterohepatic Helicobacter species from a baboon.

Renal amyloidosis due to pulmonary tuberculosis in a patient with Down syndrome.

A pulmonary-tuberculosis-related renal amyloidosis patient with Down syndrome, who presented with nephrotic syndrome, was studied.

[Renal amyloidosis caused by Ehrlichia canis]. / Durch Ehrlichia canis verursachte Nierenamyloidose.

An 8 year old, intact female, Old English Sheepdog was presented with lethargy and chronic weight loss of one year duration. The dog suffered from recurrent fever and a mild peripheral lymphadenopathy. Mild thrombocytopenia, monoclonal hyperglobulinemia and positive Ehrlichia canis antibody titer were indicative of Ehrlichiosis. The patient developed proteinuria and renal failure, which suggested the presence of glomerulopathy. Immunohistochemical staining of renal biopsy specimen demonstrated AA amyloidosis. Chronic ehrlichiosis was suspected to be the cause of the dog's renal amyloidosis.

[Mycoplasma synoviae-associated amyloid arthropathy in white leghorns: case report]. / Mycoplasma synoviae-geassocieerde gewrichtsamyloïdose bij witte leghorns: casereport.

Under field circumstances amyloid arthropathy was nerve recorded in white layers, while experimentally their brown counterparts were found to be more susceptible to the induction of amyloid arthropathy, although articular amyloid was found in a few white leghorns. In the present manuscript the first field case of amyloid arthropathy in white layers associated with Mycoplasma synoviae is reported. In the same house where the white birds were housed, brown layers were present. The condition was much more severe in the latter chickens. The different susceptibility between both breeds is discussed in view of previously performed research.

Molecular epidemiology of unilateral amyloid arthropathy in broiler breeders associated with Enterococcus faecalis.

Although symmetrical polyarticular amyloidosis has been described extensively in brown layers, spontaneous unilateral amyloid arthropathy has not been described previously in chickens. Birds from nine flocks of broiler parent stock (PS) had unilateral lameness associated with severe swelling of the left hock joint and the caudal aspect of the metatarsus. Gross pathology was restricted to the left hock joint and the left digital flexor tendons in almost all cases, suggesting an association with administration of Marek's disease vaccine. Amyloid deposits were found in 83% (25/30) of affected joints by histological examination of Congo red stained sections. Systemic amyloidosis, involving mainly the liver and spleen, was found in 59% (10/17) of birds. Enterococcus faecalis was isolated from joints in 77% (23/30) of cases and Staphylococcus aureus was isolated from the joint in one case (1/30). Thirty-five E. faecalis isolates from joints, tendons and blood samples from birds in five affected PS flocks were compared using pulsed-field gel electrophoresis (PFGE) to separate genomic fragments after digestion with SmaI. All but one isolate had identical or closely related restriction endonuclease digestion (RED) patterns that were very similar to a known arthropathic and amyloidogenic E. faecalis isolate. A further 30 E. faecalis isolates from seven grandparent stock (GPS) flocks and two isolates from two unaffected PS flocks of the same genetic background were analysed by PFGE. Among these isolates, 11 originating from four GPS flocks had RED patterns identical to or closely related to the reference amyloid-inducing strain. Moreover, one E. faecalis isolate from amyloidotic joints of brown layers housed in California, USA was included in the analysis and appeared to be identical to the reference strain. This study showed that the E. faecalis isolates involved in these outbreaks of unilateral amyloid arthropathy in broiler breeders belonged to the same clone as that responsible for outbreaks in brown layers.

Renal amyloidosis secondary to tuberculosis of cecum.

Renal amyloidosis can occur as a primary or secondary, systemic or localized disorder. It is defined as a chronic infiltrative disorder characterized by impaired organ function caused by extracellular insoluble protein fibrils. Although colonic tuberculosis is not uncommon, the occurrence of reactive renal amyloidosis in such patients is not as prevalent. We report a single case of renal amyloidosis in a patient with tuberculosis of the cecum who presented with nephrotic syndrome.