Disinhibiting neurons in the dorsomedial hypothalamus delays the onset of exertional fatigue and exhaustion in rats exercising in a warm environment.

Stimulants cause hyperthermia, in part, by increasing heat generation through exercise. Stimulants also delay the onset of fatigue and exhaustion allowing animals to exercise longer. If used in a warm environment, this combination (increased exercise and decreased fatigue) can cause heat stroke.

Treadmill running restores MDMA-mediated hyperthermia prevented by inhibition of the dorsomedial hypothalamus.

The contribution of exercise to hyperthermia mediated by MDMA is not known. We recently showed that inhibiting the dorsomedial hypothalamus (DMH) attenuated spontaneous locomotion and hyperthermia and prevented deaths in rats given MDMA in a warm environment. The goal of this study was to confirm that restoring locomotion through a treadmill would reverse these effects thereby confirming that locomotion mediated by the DMH contributes to MDMA-mediated hyperthermia.

Inhibition of the dorsomedial hypothalamus, but not the medullary raphe pallidus, decreases hyperthermia and mortality from MDMA given in a warm environment.

The central mechanisms through which MDMA mediates life-threatening hyperthermia when taken in a warm environment are not well described. It is assumed that MDMA alters normal thermoregulatory circuits resulting in increased heat production through interscapular brown adipose tissue (iBAT) and decreased heat dissipation through cutaneous vasoconstriction. We studied the role of the dorsomedial hypothalamus (DMH) and medullary raphe pallidus (mRPa) in mediating iBAT, tail blood flow, and locomotor effects produced by MDMA.

The Ergogenic Effect of Amphetamine.

Amphetamine (Amp) increases exercise duration. It is thought to do so by masking fatigue, but there have been very few studies looking at the effect of amphetamine on VO and running economy. Furthermore, it is unknown if amphetamine's effect on exercise duration occurs in a warm environment.

Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA.

Acute and chronic complications from the substituted amphetamine 3,4-methylenedioxymethamphetamine (MDMA) are linked to activation of the hypothalamic-pituitary-adrenal (HPA) axis. How MDMA activates the HPA axis is not known. HPA responses to stress are known to be mediated through the paraventricular (PVH) hypothalamus and to involve serotonin-1a (5-HT1A) receptors.

All-trans retinoic acid in combination with primaquine clears pneumocystis infection.

Pneumocystis pneumonia (PcP) develops in immunocompromised patients. Alveolar macrophages play a key role in the recognition, phagocytosis, and degradation of Pneumocystis, but their number is decreased in PcP. Our study of various inflammatory components during PcP found that myeloid-derived suppressor cells (MDSCs) accumulate in the lungs of mice and rats with Pneumocystis pneumonia (PcP).

Life-threatening hyperkalemia from cream of tartar ingestion.

Introduction: Cream of tartar (potassium bitartrate) has a long history as a cooking aid and medicinal purgative. Despite containing large amounts of potassium, there are no well-documented cases of it causing toxicity. We report two cases in which intentional ingestions of cream of tartar resulted in life-threatening hyperkalemia.

Accumulation of myeloid-derived suppressor cells in the lungs during Pneumocystis pneumonia.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of hematopoietic precursors with the ability to adversely affect host immunity. They have been shown to accumulate in pathological conditions, such as cancer and some microbial diseases. In the mouse and rat models of Pneumocystis pneumonia (PcP), we found a distinct population of cells with MDSC-like morphology in the bronchoalveolar lavage (BAL) fluid, constituting up to 50% of the total cells in BAL fluid.

The orexin-1 receptor antagonist SB-334867 decreases sympathetic responses to a moderate dose of methamphetamine and stress.

We recently discovered that inhibiting neurons in the dorsomedial hypothalamus (DMH) attenuated hyperthermia, tachycardia, hypertension, and hyperactivity evoked by the substituted amphetamine 3, 4-methylenedioxymethamphetamine (MDMA). Neurons that synthesize orexin are also found in the region of the DMH. As orexin and its receptors are involved in the regulation of heart rate and temperature, they would seem to be logical candidates as mediators of the effects evoked by amphetamines.

Defective nitric oxide production by alveolar macrophages during Pneumocystis pneumonia.

The effect of nitric oxide (NO) on Pneumocystis (Pc) organisms, the role of NO in the defense against infection with Pc, and the production of NO by alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP) were investigated. The results indicate that NO was toxic to Pc organisms and inhibited their proliferation in culture. When the production of NO was inhibited by intraperitoneal injection of rats with the nitric oxide synthase inhibitor L-N(5)-(1-iminoethyl) ornithine, progression of Pc infection in immunocompetent rats was enhanced.

Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages.

Background: Pneumocystis pneumonia is a common opportunistic disease in AIDS patients. The alveolar macrophage is an important effector cell in the clearance of Pneumocystis organisms by phagocytosis. However, both the number and phagocytic activity of alveolar macrophages are decreased in Pneumocystis infected hosts.

Downregulation of PU.1 leads to decreased expression of Dectin-1 in alveolar macrophages during Pneumocystis pneumonia.

Dectin-1 is an important macrophage phagocytic receptor recognizing fungal beta-glucans. In this study, the mRNA levels of the Dectin-1 gene were found to be decreased by 61% in alveolar macrophages (AMs) from Pneumocystis-infected mice. The expression of Dectin-1 protein on the surface of these cells was also significantly decreased.

Polyamine transport as a target for treatment of Pneumocystis pneumonia.

Polyamine levels are greatly increased in alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP), leading to increased production of H(2)O(2), which causes AMs to undergo apoptosis. One of the mechanisms by which polyamine levels in AMs are elevated is enhanced uptake of exogenous polyamines. In this study, the possibility of targeting polyamine uptake as a treatment for PCP was examined.

Effects of decreased calmodulin protein on the survival mechanisms of alveolar macrophages during Pneumocystis pneumonia.

Pneumocystis infection causes increased intracellular levels of reactive oxygen species (ROS) and the subsequent apoptosis of alveolar macrophages (Amø). Assessments of key prosurvival molecules in Amø and bronchoalveolar lavage fluids from infected rats and mice showed low levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and reduced activation of phosphoinositide-3 kinase (PI-3K). Ubiquitous calcium-sensing protein calmodulin protein and mRNA levels were also reduced in Amø during Pneumocystis pneumonia (Pcp).

Pneumocystis mediates overexpression of antizyme inhibitor resulting in increased polyamine levels and apoptosis in alveolar macrophages.

Pneumocystis pneumonia (PcP) is the most common opportunistic disease in immunocompromised patients. Alveolar macrophages are responsible for the clearance of Pneumocystis organisms; however, they undergo a high rate of apoptosis during PcP due to increased intracellular polyamine levels. In this study, the sources of polyamines and mechanisms of polyamine increase and polyamine-induced apoptosis were investigated.

Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia.

Pneumocystis pneumonia (PcP) is marked by substantial inflammatory damage to the lung. We have found that Toll-like receptor 2 (TLR2) mediates macrophage inflammatory responses to Pneumocystis and hypothesized that TLR2 deficiency would lead to less severe inflammation and milder lung injury during PcP. Histopathology examination showed that TLR2-/- mice with PcP indeed exhibited milder pulmonary inflammation.

Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia.

The number of alveolar macrophages is decreased during Pneumocystis pneumonia (Pcp), partly because of activation of apoptosis in these cells. This apoptosis occurs in both rat and mouse models of Pcp. Bronchoalveolar lavage (BAL) fluids from Pneumocystis-infected animals were found to contain high levels of polyamines, including spermidine, N1-acetylspermine, and N1-acetylspermidine.