High Incidence of Metastatic Infections in Panton-Valentine Leucocidin-Negative, Community-Acquired Methicillin-Resistant Staphylococcus aureus Bacteremia: An 11-Year Retrospective Study in Japan.

Panton-Valentine leucocidin (PVL)-negative community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was originally disseminated in Japan and has since replaced healthcare-associated MRSA (HA-MRSA). However, the clinical characteristics of CA-MRSA bacteremia (CA-MRSAB) compared with those of HA-MRSA bacteremia (HA-MRSAB) are unknown. We aim to clarify differences and investigate associations between the clinical manifestations and virulence genes associated with plasma-biofilm formation in PVL-negative CA-MRSA. From 2011 to 2021, when CA-MRSA dramatically replaced HA-MRSA, 79 MRSA strains were collected from blood cultures and analyzed via SCCmec typing and targeted virulence gene (lukSF-PV, cna, and fnbB) detection. The incidence of metastatic infection was significantly higher in CA-MRSAB than in HA-MRSAB. PVL genes were all negative, although cna and fnbB were positive in 55.6% (20/36) and 50% (18/36) of CA-MRSA strains and 3.7% (1/27) and 7.4% (2/27) of HA-MRSA strains, respectively. cna and fnbB carriage were not associated with the development of metastatic infections in MRSAB; however, the bacteremia duration was significantly longer in CA-MRSAB harboring cna. CA-MRSAB may be more likely to cause metastatic infections than HA-MRSAB. Since CA-MRSA is dominant in Japan, suspected metastatic infection foci should be identified by computed tomography, magnetic resonance imaging, and echocardiography when treating MRSAB.

Insulin inhibits glucagon-induced glycogenolysis normally in perivenous hepatocytes of Wistar fatty rats.

Wistar fatty (WF) rats are obese, hyperinsulinemic and hyperglycemic, and thus a model of type 2 diabetes mellitus. Since we have found that insulin specifically inhibits glucagon-induced glycogenolysis in perivenous hepatocytes (PVH) from normal rats, we examined the inhibitory effect of insulin on glucagon-induced glycogenolysis in PVH of hyperinsulinemic WF rats. Basal glucose release was 64.0+/-4.1 nmol/mgprotein/30 min from PVH of lean littermates (WL rats) and 137.0+/-19.3 nmol/mgprotein/30 min from that of WF rats (p<0.01). These were proportional to the glycogen content in PVH of WL and WF rats (56.7+/-7.2 and 131.0+/-20.3 microg/mgprotein, p<0.01), and increased to 109.0+/-8.8 and 225.8+/-17.9nmol/mgprotein/30min, respectively, with 0.1 nmol/l glucagon. When 10 nmol/l insulin was coincubated, 0.1 nmol/l glucagon-induced increase in glucose release decreased to 93.3+/-10.9 nmol/mgprotein/30 min in PVH of WL rats (p<0.01) and to 181+/-20.7 nmol/mgprotein/30 min in PVH of WF rats (p<0.01). Thus, insulin antagonized glucagon-induced glycogenolysis in PVH similarly between WL and WF rats, to 56.7+/-13.3% and to 46.1+/-7.5%, respectively. Thus, the antagonizing effect of insulin on glucagon-induced increase in glycogenolysis was preserved in PVH of hyperinsulinemic and hyperglycemic WF rats.

Glucagon-like peptide-1 inhibits glucagon-induced glycogenolysis in perivenous hepatocytes specifically.

Hepatocytes form the hepatic acinus as a unit of microcirculation. Following the bloodstream, at least two different zones can be discerned: the periportal (PPH) and the perivenous (PVH) zones. Recently, we found that insulin inhibits glucagon-induced glycogenolysis in PVH specifically. We therefore investigated the region-specific functional effects of glucagon-like peptide-1 (GLP-1), which is known to have an insulin-like activity, on glucagon-induced glycogenolysis in isolated PPH and PVH prepared by the digitonin-collagenase method. GLP-1 inhibited 0.1 nM glucagon-induced increase in glucose release from the PVH of fed rats specifically (p < 0.01) and had an additive effect with insulin. Insulin binding did not differ between PPH and PVH of fed rats. GLP-1 did not displace [125I]-glucagon binding to the purified hepatic cell membrane. Thus, it is directly confirmed that GLP-1 has an insulin-like activity in the liver.