Decreasing Vitamin C Intake, Low Serum Vitamin C Level and Risk for US Adults with Diabetes.

Vitamin C (VC) intakes, serum VC, fasting plasma glucose, and A1c levels of 25,206 adult men and 26,944 adult women with 6807 type 2 and 428 type 1 diabetes from the NHANES database between 1999 and 2018 were analyzed. Our hypothesis is that low VC intake and serum VC level may be a health risk for US adults with diabetes. Analyses revealed total VC intake below the estimated average requirement (EAR) increased from 38.1% to 46.5% between 1999-2018. VC intake and serum VC levels were inversely associated with markers of pre-diabetes and type 2 diabetes, namely, fasting plasma glucose and A1c levels. Risks of type 2 diabetes increased in adults with VC intake below the EAR and with no VC supplement (odds ratio 1.20, 95% CI 1.1-1.3 and 1.28, 95% CI 1.18-1.40, respectively). Median survivor years of diabetic adults with lower and deficient serum VC were shorter than that of diabetic adults with normal serum VC. Mortality risks of type 2 diabetes with low VC intake and/or deficient serum VC levels were elevated compared to those with adequate VC intake and normal serum VC (HR 1.25, 95% CI 1.05-1.49 and 1.84, 95% CI 1.10-3.08, respectively). Observation of declining VC intake and deleterious consequences of low serum VC in US adults with diabetes suggests encouragement of VC intake, including VC supplementation of 500-1000 mg/day, may be beneficial for pre-diabetic and diabetic US adults.

Sr_{2}MoO_{4} and Sr_{2}RuO_{4}: Disentangling the Roles of Hund's and van Hove Physics.

Sr_{2}MoO_{4} is isostructural to the unconventional superconductor Sr_{2}RuO_{4} but with two electrons instead of two holes in the Mo/Ru-t_{2g} orbitals. Both materials are Hund's metals, but while Sr_{2}RuO_{4} has a van Hove singularity in close proximity to the Fermi surface, the van Hove singularity of Sr_{2}MoO_{4} is far from the Fermi surface. By using density functional plus dynamical mean-field theory, we determine the relative influence of van Hove and Hund's metal physics on the correlation properties. We show that theoretically predicted signatures of Hund's metal physics occur on the occupied side of the electronic spectrum of Sr_{2}MoO_{4}, identifying Sr_{2}MoO_{4} as an ideal candidate system for a direct experimental confirmation of the theoretical concept of Hund's metals via photoemission spectroscopy.

Disaster Preparedness: Biological Threats and Treatment Options.

Biological disasters can be natural, accidental, or intentional. Biological threats have made a lasting impact on civilization. This review focuses on agents of clinical significance, bioterrorism, and national security, specifically Category A agents (anthrax, botulism, plague, tularemia, and smallpox), as well as briefly discusses other naturally emerging infections of public health significance, Ebola virus (also a Category A agent) and Zika virus. The role of pharmacists in disaster preparedness and disaster response is multifaceted and important. Their expertise includes clinical knowledge, which can aid in drug information consultation, patient-specific treatment decision making, and development of local treatment plans. To fulfill this role, pharmacists must have a comprehensive understanding of medical countermeasures for these significant biological threats across all health care settings. New and reemerging infectious disease threats will continue to challenge the world. Pharmacists will be at the forefront of preparedness and response, sharing knowledge and clinical expertise with responders, official decision makers, and the general public.

Systemic lipopolysaccharide plus MPTP as a model of dopamine loss and gait instability in C57Bl/6J mice.

In most environmental models of Parkinson's disease (PD), a single neurodegenerative agent is introduced to cause nigrostriatal dopamine depletion. However, cell loss in human PD often might derive, at least in part, from multiple toxins or vulnerabilities, any one of which alone does not inevitably lead to chronic dopamine depletion. In the present research, male C57BL/6J mice were systemically administered the inflammatory bacterial endotoxin, lipopolysaccharide (LPS) and the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) alone or in combination and the behavior as well as striatal dopamine levels were compared to saline-treated mice. Mice in the combination (LPS+MPTP) group, but not in the single-factor groups, showed both dopamine depletion and parkinsonian symptoms, i.e., reduced stride length, at 4 months post-injection. MPTP alone acutely reduced striatal dopamine levels but this effect was transient as striatal dopamine recovered to normal levels after time (4 months). The LPS-only group showed no dopamine depletion or reduced stride length. These data are consistent with the view that nigrostriatal dopamine neurons might succumb after time to multiple toxic agents that independently may have only a transient, adverse effect.

Spiny mice (Acomys cahirinus) do not respond to thymus-independent type 2 antigens.

Analysis of the immune system of spiny mice (Acomys cahirinus) has been limited. Originally grouped with Mus, Acomys has recently been placed closer to Meriones (gerbils). This study compared immunity in Acomys, Mus, and Meriones. Lymphocytes from all rodents examined proliferated in response to mitogen and superantigen stimulation. Only Mus T cells responded to anti-CD3 stimulation. Acomys, like Meriones, and Mus that express xid, did not respond to thymus-independent type 2 antigens. Flow cytometric analyses revealed that T cell-specific MAbs did not bind Acomys or Meriones lymphocytes. The B cell-specific anti-CD45R (B220) MAb detected all rodent B cells and revealed the absence of a CD45R(lo) subset in the peritoneal cavity of Acomys and Meriones. Bone marrow from Acomys and Meriones failed to reconstitute B cell function in SCID mice. Thus, in terms of immunity, Acomys appears to be more similar to Meriones than Mus.

Corticosterone modulates auditory gating in mouse.

Previous studies suggest that circulating glucocorticoids may influence the encoding and processing of sensory stimuli. The current study investigated this hypothesis by measuring the generation (amplitude), gating (recovery cycle), and sensitivity (intensity function) of auditory evoked responses in C57BL/6 mice treated with chronic corticosterone (0, 1, 5, 15, or 30 mg/kg/day for 14 days). We found that low-dose corticosterone (5 but not 1 mg/kg/day) enhanced the amplitude and improved gating of evoked potentials without affecting the intensity function. In comparison, higher doses (15 and 30 mg/kg/day) decreased the amplitude and impaired gating of evoked potentials, also without altering the stimulus intensity function. At all doses, lower amplitudes of evoked potentials were significantly correlated with higher circulating corticosterone levels. These data highlight the need to consider serum glucocorticoid levels when assessing human disease states associated with aberrations of information processing such as schizophrenia and depression.

Ketamine produces lasting disruptions in encoding of sensory stimuli.

The current study analyzed the acute, chronic, and lasting effects of ketamine administration in four inbred mouse strains (C3H/HeHsd, C57BL/6Hsd, FVB/Hsd, and DBA/2Hsd) to evaluate vulnerability to ketamine as a drug of abuse and as a model of schizophrenia. Serum half-life of ketamine was similar between all strains (approximately 13 min). Also, the ratio of brain-to-serum ketamine levels was 3:1. Examination of multiple phases of auditory processing using auditory-evoked potentials (AEPs) following acute ketamine (0, 5, and 20 mg/kg) treatment revealed C3H/HeHsd mice to be most vulnerable to ketamine-induced alterations in AEPs, whereas FVB/Hsd mice exhibited the least electrophysiological sensitivity to ketamine. Overall, the precortical P1-evoked potential component increased in amplitude and latency, whereas the cortically generated N1 and P2 components decreased in amplitude and latency following acute ketamine across all strains. Brain catecholamine analyses indicated that ketamine decreased hippocampus epinephrine levels in C3H/HeHsd but elevated hippocampus epinephrine levels in FVB/Hsd, suggesting one potential mechanism for AEP vulnerability to ketamine. Based on results of the acute study, the immediate and lasting effects of chronic low-dose ketamine on AEPs were examined among C3H/HeHsd (sensitive) and FVB/Hsd (insensitive) mice. We observed a decrement of the N1 amplitude that persisted at least 1 week after the last exposure to ketamine across both strains. This lasting deficit in information processing occurred in the absence of acute changes among the FVB/Hsd mice. Implications for both ketamine abuse and N-methyl-D-aspartate hypofunction models of schizophrenia are discussed.

Noradrenergic responses of peripheral organs to cyclophosphamide in mice.

To determine if the chemotherapeutic drug cyclophosphamide influences the activity of the sympathetic nervous system, the effects of cyclophosphamide on norepinephrine concentration in the heart, adrenal gland, spleen, and thymus gland were evaluated. Male BALB/cByJ mice were administered a single injection of cyclophosphamide (15, 50, or 100 mg/kg, i.p) or saline-vehicle. Organs were collected 72 or 120 h after injection and norepinephrine concentrations were determined by high pressure liquid chromatography with electrochemical detection. Cyclophosphamide reduced spleen, thymus gland, and heart mass while also elevating spleen and thymus gland norepinephrine concentrations (both pmoles/mg tissue and pmoles/mg protein) in a dose- and time-dependent manner. Norepinephrine concentrations in heart and adrenal gland were not altered by cyclophosphamide at any drug dose or time point. Dose- and time-dependent cyclophosphamide-mediated changes in peripheral norepinephrine levels in the spleen and thymus gland are interesting because subjects administered cyclophosphamide may be more susceptible to opportunistic infections, not only because the drug is antineoplastic, but also because the drug alters nervous system-immune system communication and the neurochemical milieu in which surviving cells interact.

Cyclophosphamide induces dose- and time-dependent elevations in spleen norepinephrine levels of BALB/c mice.

Chemotherapeutic drugs may not only kill rapidly dividing cells but may also alter the extracellular environment of surviving cells. We investigated the possibility that cyclophosphamide might alter the noradrenergic environment of the spleen. Male BALB/cByJ mice were administered a single injection of cyclophosphamide (0, 15, 50, or 100 mg/kg). Seventy-two hours after injection animals receiving 50 or 100 but not 15 mg/kg experienced elevated norepinephrine concentrations (pmol/mg) compared to animals given 0 mg/kg. The time course of changes in norepinephrine concentration was investigated 24-216 h after administration of 50 mg/kg cyclophosphamide; norepinephrine took 48 h to elevate, remained elevated for 48-96 h, and returned to vehicle-treated levels by 120 h. Cyclophosphamide in both experiments reduced spleen mass but did not alter total norepinephrine/spleen. These results suggest that low doses of cyclophosphamide can increase the norepinephrine available to influence cell-cell interactions in the spleen.