VIP Regulates the Development & Proliferation of Treg in vivo in spleen

<p>Abstract</p> <p>Background</p> <p>Mounting evidence supports a key role for VIP as an anti-inflammatory agent and promoter of immune tolerance. It suppresses TNF-α and other inflammatory cytokines and chemokines, upregulates anti-inflammatory IL-10, and promotes immune tolerant cells called T regulatory (Treg) cells. VIP KO mice have recently been demonstrated to have spontaneous airway and pulmonary perivascular inflammatory responses, as part of asthma-like and pulmonary hypertension phenotypes, respectively. Both inflammatory responses are correctable with VIP. Focusing on this model, we have now investigated the influence of VIP not only on inflammatory cells but also on Treg cells.</p> <p>Methods</p> <p>Using flow cytometric analysis, we examined the relative preponderance of CD25+CD4+ cells and anti-inflammatory Treg cells, in extracts of thymus and spleen from VIP KO mice (5 VIP KO; 5 VIP KO+ VIP; 10 wild-type). This method allowed antibody-based flow cytometric identification of Treg cells using surface markers CD25 and CD4, along with the: 1) intracellular activation marker FoxP3; and 2) Helios, which distinguishes cells of thymic versus splenic derivation.</p> <p>Conclusions</p> <p>Deletion of the VIP gene results in: 1) CD25+CD4- cell accumulation in the thymus, which is corrected by VIP treatment; 2) more Treg in thymus lacking Foxp3 expression, suggesting VIP is necessary for immune tolerance; and, 3) a tendency towards deficiency of Treg cells in the spleen, which is normalized by VIP treatment. Treg lacking Helios are induced by VIP intrasplenically rather than by migration from the thymus. These results confirm the dual role of VIP as an anti-inflammatory and immune tolerance-promoting agent.</p

Gross Hematuria and Lower Urinary Tract Symptoms Associated With Military Burn Pits Exposures in US Veterans Deployed to Iraq and Afghanistan

OBJECTIVE: The aim of the study is to describe rates of hematuria and other lower urinary tract symptoms, including self-reported cancer rates, among veterans postburn pits emissions exposure during deployment to Iraq and Afghanistan. METHODS: US post-9/11 veterans with burn pits emissions exposure confirmed via DD214 forms in the Burn Pits360.org Registry were sent a modified survey. Data were deidentified and anonymously coded. RESULTS: Twenty-nine percent of the 155 respondents exposed to burn pits self-reported seeing blood in their urine. The average index score of our modified American Urological Association Symptom Index Survey was 12.25 (SD, 7.48). High rates of urinary frequency (84%) and urgency (76%) were self-reported. Bladder, kidney, or lung cancers were self-reported in 3.87%. CONCLUSIONS: US veterans exposed to burn pits are self-reporting hematuria and other lower urinary tract symptoms

A plane screw fixation is a nidus for Paecilomyces sinusitis in a patient with aspirin exacerbated respiratory disease

Titanium plane screw fixation of the frontal sinus is an approach used by otolaryngologists to obliterate this space in an attempt to reduce sinus infections. In this case, however, the titanium used became a nidus of infection which cultured the fungus Paecilomyces. The patient also had a hypersensitivity reaction to mold with positive skin tests and IgE, as well as eosinophilic esophagitis. Treatment entailed anti-fungals, anti-IgE, and fungal immunotherapy to multiple fungal antigens prevalent to the geographic region. The patient also had aspirin exacerbated respiratory disease which responded to aspirin desensitization. Her symptoms resolved after 3 months

Allergic Reaction to Mint Leads to Asthma

Respiratory and cutaneous adverse reactions to mint can result from several different mechanisms including IgE-mediated hypersensitivity, delayed-type hypersensitivity (contact dermatitis), and nonimmunologic histamine release. Reactions to cross-reacting plants of the Labiatae family, such as oregano and thyme, as well as to the chemical turpentine, may clue the clinician in on the diagnosis of mint allergy. Contact dermatitis can result from menthol in peppermint. Contact allergens have been reported in toothpastes, which often are mint-flavored. Allergic asthma from mint is less well-recognized. A case of a 54-year-old woman with dyspnea on exposure to the scent of peppermint is presented in whom mint exposure, as seemingly innocuous as the breath of others who had consumed Tic Tac candies, exacerbated her underlying asthma. This case highlights the importance of testing with multiple alternative measures of specific IgE to mint, including skin testing with mint extract, and skin testing with fresh mint leaves. Additionally, this cases suggests that asthma can result from inhaling the scent of mint and gives consideration to obtaining confirmatory pre- and postexposure pulmonary function data by both impulse oscillometry and spirometry

Emerging Novel Therapies for Heart Failure

Heart function fails when the organ is unable to pump blood at a rate proportional to the body's need for oxygen or when this function leads to elevated cardiac chamber filling pressures (cardiogenic pulmonary edema). Despite our sophisticated knowledge of heart failure, even so-called ejection fraction-preserved heart failure has high rates of mortality and morbidity. So, novel therapies are sorely needed. This review discusses current standard therapies for heart failure and launches an exploration into emerging novel treatments on the heels of recently-approved sacubitril and ivbradine. For example, Vasoactive Intestinal Peptide (VIP) is protective of the heart, so in the absence of VIP, VIP knockout mice have dysregulation in key heart failure genes: 1) Force Generation and Propagation; 2) Energy Production and Regulation; 3) Ca +2 Cycling; 4) Transcriptional Regulators. VIP administration leads to coronary dilation in human subjects. In heart failure patients, VIP levels are elevated as a plausible endogenous protective effect. With the development of elastin polymers to stabilize VIP and prevent its degradation, VIP may therefore have a chance to satisfy the unmet need as a potential treatment for acute heart failure

Clozapine-associated cardiac dysfunction during a gastroenteritis outbreak

We report that two young adult patients who were initiated with clozapine for severe psychosis during a hospital-wide gastroenteritis outbreak went into severe shock. Neither patient had troponin elevation. Each required left ventricular assist device support for myocarditis. Endomyocardial biopsy revealed lymphocytic myocarditis in one patient and eosinophilic myocarditis in the other. The former patient expired. Polymerase chain reaction testing was negative for Coxsackie virus. These two patients illustrate that myocarditis can occur at usual incipient doses and that there may be an epidemiologic risk associated with gastroenteritis. Although the white blood cell (WBC) count is expected to decrease with clozapine, these patients had persistently elevated WBC counts. In conclusion, physicians should exercise caution when prescribing clozapine, especially for those with diarrhea

VIP gene deletion in mice causes cardiomyopathy associated with upregulation of heart failure genes.

RATIONALE: Vasoactive Intestinal Peptide (VIP), a pulmonary vasodilator and inhibitor of vascular smooth muscle proliferation, is absent in pulmonary arteries of patients with idiopathic pulmonary arterial hypertension (PAH). We previously determined that targeted deletion of the VIP gene in mice leads to PAH with pulmonary vascular remodeling and right ventricular (RV) dilatation. Whether the left ventricle is also affected by VIP gene deletion is unknown. In the current study, we examined if VIP knockout mice (VIP(-/-)) develop both right (RV) and left ventricular (LV) cardiomyopathy, manifested by LV dilatation and systolic dysfunction, as well as overexpression of genes conducive to heart failure. METHODS: We examined VIP(-/-)and wild type (WT) mice using Magnetic Resonance Imaging (MRI) for evidence of cardiomyopathy associated with biventricular dilation and wall thickness changes. Lung tissue from VIP(-/-) and WT mice was subjected to whole-genome gene microarray analysis. RESULTS: Lungs from VIP(-/-) mice showed overexpression of cardiomyopathy genes: Myh1 was upregulated 224 times over WT, and Mylpf was increased 72 fold. Tnnt3 was increased 105 times and tnnc2 181 fold. Hearts were dilated in VIP(-/-) mice, with thinning of LV wall and increase in RV and LV chamber size, though RV enlargement varied. Weights of VIP(-/-) mice were consistently lower. CONCLUSIONS: Critically-important heart failure-related genes are upregulated in VIP(-/-) mice associated with the spontaneous cardiomyopathy phenotype, involving both left and right ventricles, suggesting that loss of the VIP gene orchestrates a panoply of pathogenic genes which are detrimental to both left and right cardiac homeostasis