Epidemiology, clinical and laboratory findings of leptospirosis in Southwestern Greece.

Background: Leptospirosis is a zoonosis with global distribution. The aim of the present study was to determine epidemiological, clinical and laboratory characteristics of leptospirosis in Greece.Methods: We retrospectively reviewed the clinical and laboratory profile as well as the outcome of all adults with confirmed leptospirosis in our Tertiary Referral centre in Southwestern Greece from 2013 to 2017.Results: Thirty-one men and fourteen women (mean age: 55.5 ± 13.8 years), were diagnosed with leptospirosis based on compatible clinical course and positive serology for IgM antibodies. Thirty-two (71.1%) lived in rural areas and the majority of infections (88.8%) were autochthonous, acquired in Southwestern Greece. Eighteen patients (40%) reported occupational exposure. The most prevalent clinical feature was fever (93.3%), followed by headache (66%), hematuria (31.1%), conjunctival suffusion and hepatomegaly (26.6%), dyspnoea, tachypnoea and splenomegaly (17.7%). One patient died due to pulmonary hemorrhage. Increased CRP (median 19 mg/dL) was the most common laboratory abnormality detected (93.3%), followed by thrombocytopenia (80%), increased aminotransferases (AST in 73.3% and ALT in 66.6%), anemia (66.6%) and hematuria (>100 RBC per high power field) in 66.6%. Empiric treatment with at least one active antibiotic against Leptospira was administered in 40 patients (88.8%).Conclusions: We found a higher disease incidence in our area compared to previous reports in Greece. Clinical signs of leptospirosis are diverse and generally nonspecific. Further epidemiological studies conducted ideally at a national level are required to determine the true disease incidence and better understand risk factors associated with unfavorable outcomes.

Replication of Brucella melitensis inside primary human monocytes depends on mitogen activated protein kinase signaling.

The clinical course of infections caused by Brucella is linked to its capacity to modulate the initial immune response of macrophages in order to ensure its intracellular replication. Signal transduction pathways implicated in the survival of Brucella in human cells are not completely elucidated. We herein investigated the involvement of the TLR-MAPK-dependent signaling pathways in the survival of Brucella in primary human monocytes using live clinical strains of Brucella melitensis. B. melitensis caused a delayed, TLR2 dependent MAPK activation. Specific MAPK inhibitors for p38 (SB203580), ERK1/2 (PD98059) and JNK (SP600125) or the anti-TLR2 blocking Ab inhibited both inflammatory and anti-inflammatory responses characterized by TNF-α, IL-6 and IL-10 production. Intracellular replication of B. melitensis was mainly dependent on p38 and JNK activation and not affected by IL-10 levels. These are the first evidence to support that survival of B. melitensis inside human monocytes depends on interplay among the different MAPK family members, activated through TLR2, in spite of an initial pro-inflammatory response.

Apolipoprotein A-I modulates processes associated with diet-induced nonalcoholic fatty liver disease in mice.

Apolipoprotein A-I (apoA-I) is the main protein of high-density lipoprotein (HDL). We investigated the involvement of apoA-I in diet-induced accumulation of triglycerides in hepatocytes and its potential role in the treatment of nonalcoholic fatty liver disease (NAFLD). ApoA-I-deficient (apoA-I(-/-)) mice showed increased diet-induced hepatic triglyceride deposition and disturbed hepatic histology while they exhibited reduced glucose tolerance and insulin sensitivity. Quantification of FASN (fatty acid synthase) [corrected], DGAT-1 (diacylglycerol O-acyltransferase 1), and PPARγ (peroxisome proliferator-activated receptor γ) mRNA expression suggested that the increased hepatic triglyceride content of the apoA-I(-/-) mice was not due to de novo synthesis of triglycerides. Similarly, metabolic profiling did not reveal differences in the energy expenditure between the two mouse groups. However, apoA-I(-/-) mice exhibited enhanced intestinal absorption of dietary triglycerides (3.6 ± 0.5 mg/dL/min for apoA-I(-/-) versus 2.0 ± 0.7 mg/dL/min for C57BL/6 mice, P < 0.05), accelerated clearance of postprandial triglycerides and a reduced rate of hepatic very low density lipoprotein (VLDL) triglyceride secretion (9.8 ± 1.1 mg/dL/min for apoA-I(-/-) versus 12.5 ± 1.3 mg/dL/min for C57BL/6 mice, P < 0.05). In agreement with these findings, adenovirus-mediated gene transfer of apoA-I(Milano) in apoA-I(-/-) mice fed a Western-type diet for 12 wks resulted in a significant reduction in hepatic triglyceride content and an improvement of hepatic histology and architecture. Our data extend the current knowledge on the functions of apoA-I, indicating that in addition to its well-established properties in atheroprotection, it is also an important modulator of processes associated with diet-induced hepatic lipid deposition and NAFLD development in mice. Our findings raise the interesting possibility that expression of therapeutic forms of apoA-I by gene therapy approaches may have a beneficial effect on NAFLD.