Clostridium sordellii: A Cause of Toxic Shock Syndrome After a Breach in the GI Tract.

Clostridium sordellii is a highly virulent microorganism that causes serious infections, most commonly of the uterus and perineum. It has a high associated mortality rate due to the various toxins that it produces. A review of the literature suggests that knowledge surrounding its proper management is limited. This report describes a case of Clostridium sordellii causing toxic shock syndrome posttranslocation through the GI tract. A 69-year-old man with a past medical history of renal cell carcinoma and small bowl obstruction complicating transverse colostomy presented to the emergency room with back pain and rigors. Vital signs showed that he was in hemodynamic shock, and imaging revealed a left renal mass invading the adjacent splenic flexure of the colon. There was also a significant leukemoid reaction. After receiving a series of antibiotics, blood cultures revealed Clostridium sordellii as the pathogen of interest. As the first report of its kind, we identify a unique presentation of this organism, serving as a primary example of a different setting that clinicians should be aware of while at the same time highlighting a successful course of therapy for this often deadly organism.

Central Apolipoprotein A-IV Stimulates Thermogenesis in Brown Adipose Tissue.

Stimulation of thermogenesis in brown adipose tissue (BAT) could have far-reaching health benefits in combatting obesity and obesity-related complications. Apolipoprotein A-IV (ApoA-IV), produced by the gut and the brain in the presence of dietary lipids, is a well-known short-term satiating protein. While our previous studies have demonstrated reduced diet-induced thermogenesis in ApoA-IV-deficient mice, it is unclear whether this reduction is due to a loss of peripheral or central effects of ApoA-IV. We hypothesized that central administration of ApoA-IV stimulates BAT thermogenesis and that sympathetic and sensory innervation is necessary for this action. To test this hypothesis, mice with unilateral denervation of interscapular BAT received central injections of recombinant ApoA-IV protein or artificial cerebrospinal fluid (CSF). The effects of central ApoA-IV on BAT temperature and thermogenesis in mice with unilateral denervation of the intrascapular BAT were monitored using transponder probe implantation, qPCR, and immunoblots. Relative to CSF, central administration of ApoA-IV significantly increased temperature and UCP expression in BAT. However, all of these effects were significantly attenuated or prevented in mice with unilateral denervation. Together, these results clearly demonstrate that ApoA-IV regulates BAT thermogenesis centrally, and this effect is mediated through sympathetic and sensory nerves.

RAMP1 and RAMP3 Differentially Control Amylin's Effects on Food Intake, Glucose and Energy Balance in Male and Female Mice.

Amylin is a pancreatic peptide, which acts as a key controller of food intake and energy balance and predominately binds to three receptors (AMY 1-3). AMY 1-3 are composed of a calcitonin core receptor (CTR) and associated receptor-activity modifying proteins (RAMPs) 1-3. Using RAMP1, RAMP3 and RAMP1/3 global KO mice, this study aimed to determine whether the absence of one or two RAMP subunits affects food intake, glucose homeostasis and metabolism. Of all the RAMP-deficient mice, only high-fat diet fed RAMP1/3 KO mice had increased body weight. Chow-fed RAMP3 KO and high-fat diet fed 1/3 KO male mice were glucose intolerant. Fat depots were increased in RAMP1 KO male mice. No difference in energy expenditure was observed but the respiratory exchange ratio (RER) was elevated in RAMP1/3 KO. RAMP1 and 1/3 KO male mice displayed an increase in intermeal interval (IMI) and meal duration, whereas IMI was decreased in RAMP3 KO male and female mice. WT and RAMP1, RAMP3, and RAMP1/3 KO male and female littermates were then assessed for their food intake response to an acute intraperitoneal injection of amylin or its receptor agonist, salmon calcitonin (sCT). RAMP1/3 KO were insensitive to both, while RAMP3 KO were responsive to sCT only and RAMP1 KO to amylin only. While female mice generally weighed less than male mice, only RAMP1 KO showed a clear sex difference in meal pattern and food intake tests. Lastly, a decrease in CTR fibers did not consistently correlate with a decrease in amylin- induced c-Fos expression in the area postrema (AP). Ultimately, the results from this study provide evidence for a role of RAMP1 in mediation of fat utilization and a role for RAMP3 in glucose homeostasis and amylin's anorectic effect.

Reduced Diet-induced Thermogenesis in Apolipoprotein A-IV Deficient Mice.

In the presence of dietary lipids, both apolipoprotein A-IV (ApoA-IV) production and brown adipose tissue (BAT) thermogenesis are increased. The effect of dietary lipid-induced AproA-IV on BAT thermogenesis and energy expenditure remains unknown. In the present study, we hypothesized that ApoA-IV knockout (ApoA-IV-KO) mice exhibited decreased BAT thermogenesis to affect energy homeostasis. To test this hypothesis, BAT thermogenesis in wildtype (WT) and ApoA-IV-KO mice fed either a standard low-fat chow diet or a high-fat diet (HFD) was investigated. When fed a chow diet, energy expenditure and food intake were comparable between WT and ApoA-IV-KO mice. After 1 week of HFD consumption, ApoA-IV-KO mice had comparable energy intake but produced lower energy expenditure relative to their WT controls in the dark phase. After an acute feeding of dietary lipids or 1-week HFD feeding, ApoA-IV-KO mice produced lower levels of uncoupling protein 1 (UCP1) and exhibited reduced expression of thermogenic genes in the BAT compared with WT controls. In response to cold exposure, however, ApoA-IV-KO mice had comparable energy expenditure and BAT temperature relative to WT mice. Thus, ApoA-IV-KO mice exhibited reduced diet-induced BAT thermogenesis and energy expenditure.