Idiopathic Copper Deficiency Induced Myeloneuropathy.

Idiopathic nutritional deficiencies are often overlooked in patients with no history of malabsorption. However, it may lead to severe neurologic dysfunction that can sometimes be irreversible. We present a case in which early recognition of copper deficiency has led to a better outcome for the patient, who presented with acute myeloneuropathy. A 45-year-old male with no significant history of malnutrition or malabsorption presented with complaints of acute encephalopathy, bilateral wrist drop, bilateral tingling and weakness in his hands as well as urinary incontinence. Workup upon arrival was nonrevealing, the patient was treated initially as presumed AIDP (acute inflammatory demyelinating polyradiculopathy), and he underwent plasmapheresis with no response. Since the patient did not respond to plasmapheresis and he had a significantly low folate levels with initial labs. Further nutritional workup was done, which revealed low copper (levels of 0.45), vitamins A, E, and B1. The patient was also tested for celiac which was negative, underwent upper endoscopy and colonoscopy which were both not significant. Decision was made to treat patient early with IV copper infusion as symptoms were deemed most likely due to copper deficiency. The patient received a total of 4 IV doses, after which the patient had a significant clinical response after infusion therapy and repeat copper levels revealed an increase as well (levels of 0.71). Prior to discharge, the patient had significant improvement in wrist drop as well as symptoms of tingling and numbness. Despite being a trace element, copper deficiency can cause significant neurologic impairment. Furthermore, early recognition has proved to be imperative in neurologic recovery and supplementation has proven to be successful in improving patient's quality of life.

New NP job search experience: Opportunities and obstacles.

ABSTRACT: This descriptive study investigated new NPs' job search experience including the job search process, employment negotiation, and compensation. The majority of new graduates found a job through networking within 3 months in a specialty practice or family medicine. Lack of experience and few available positions were employment obstacles.

Not so Element-ary: A Copper Conundrum.

Copper is an essential micronutrient required for a number of enzymatic activities. Deficiency is relatively rare as only trace amounts are needed to maintain homeostasis. Deficiencies however do occur and are most commonly seen in malabsorptive states such as after bariatric surgeries. Herein, we present an interesting case of copper deficiency diagnosed in a 70-year-old male patient post duodenal switch procedure which persisted despite aggressive oral and intravenous copper supplementation. This lack of response to supplementation prompted further evaluation, leading to a diagnosis of underlying heterozygous Wilson's disease.

Antidiabetogenic effects of chromium mitigate hyperinsulinemia-induced cellular insulin resistance via correction of plasma membrane cholesterol imbalance.

Previously, we found that a loss of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP2)-regulated filamentous actin (F-actin) structure contributes to insulin-induced insulin resistance. Interestingly, we also demonstrated that chromium picolinate (CrPic), a dietary supplement thought to improve glycemic status in insulin-resistant individuals, augments insulin-regulated glucose transport in insulin-sensitive 3T3-L1 adipocytes by lowering PM cholesterol. Here, to gain mechanistic understanding of these separate observations, we tested the prediction that CrPic would protect against insulin-induced insulin resistance by improving PM features important in cytoskeletal structure and insulin sensitivity. We found that insulin-induced insulin-resistant adipocytes display elevated PM cholesterol with a reciprocal decrease in PM PIP2. This lipid imbalance and insulin resistance was corrected by the cholesterol-lowering action of CrPic. The PM lipid imbalance did not impair insulin signaling, nor did CrPic amplify insulin signal transduction. In contrast, PM analyses corroborated cholesterol and PIP2 interactions influencing cytoskeletal structure. Because extensive in vitro study documents an essential role for cytoskeletal capacity in insulin-regulated glucose transport, we next evaluated intact skeletal muscle from obese, insulin-resistant Zucker (fa/fa) rats. Because insulin resistance in these animals likely involves multiple mechanisms, findings that cholesterol-lowering restored F-actin cytoskeletal structure and insulin sensitivity to that witnessed in lean control muscle were striking. Also, experiments using methyl-beta-cyclodextrin to shuttle cholesterol into or out of membranes respectively recapitulated the insulin-induced insulin-resistance and protective effects of CrPic on membrane/cytoskeletal interactions and insulin sensitivity. These data predict a PM cholesterol basis for hyperinsulinemia-associated insulin resistance and importantly highlight the reversible nature of this abnormality.

"Cat got your lung?": Case of a trapped lung following cat bite.

Pasturella multocida is a gram negative encapsulated facultative bacillus that has been reported to cause a wide variety of infections in humans. Empyema is rarely reported complication of P. multocida infection. Infection is usually acquired by inhalation or bite from a domestic animal, with cats and dogs being the most common sources. Isolation of organisms on culture remains gold standard for diagnosis. We describe a case of P. multocida related empyema in a patient who subsequently developed trapped lung requiring video assisted thoracoscopic surgical decortication. It was determined that the cause of this patient's empyema was likely from a bite from his own cat.

A novel membrane-based anti-diabetic action of atorvastatin.

We recently found that chromium picolinate (CrPic), a nutritional supplement thought to improve insulin sensitivity in individuals with impaired glucose tolerance, enhances insulin action by lowering plasma membrane (PM) cholesterol. Recent in vivo studies suggest that cholesterol-lowering statin drugs benefit insulin sensitivity in insulin-resistant patients, yet a mechanism is unknown. We report here that atorvastatin (ATV) diminished PM cholesterol by 22% (P<0.05) in 3T3-L1 adipocytes. As documented for CrPic, this small reduction in PM cholesterol enhanced insulin action. Replenishment of cholesterol mitigated the positive effects of ATV on insulin sensitivity. Co-treatment with CrPic and ATV did not amplify the extent of PM cholesterol loss or insulin sensitivity gain. In addition, analyses of insulin signal transduction suggest a non-signaling basis of both therapies. Our data reveal an unappreciated beneficial non-hepatic effect of statin action and highlight a novel mechanistic similarity between two recently recognized therapies of impaired glucose tolerance.

Hexosamine biosynthesis pathway flux contributes to insulin resistance via altering membrane phosphatidylinositol 4,5-bisphosphate and cortical filamentous actin.

We recently found that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP(2))-regulated filamentous actin (F-actin) polymerization was diminished in hyperinsulinemic cell culture models of insulin resistance. Here we delineated whether increased glucose flux through the hexosamine biosynthesis pathway (HBP) causes the PIP(2)/F-actin dysregulation and insulin resistance induced by hyperinsulinemia. Increased HBP activity was detected in 3T3-L1 adipocytes cultured under conditions closely resembling physiological hyperinsulinemia (5 nm insulin for 12 h) and in cells where HBP activity was amplified by 2 mm glucosamine (GlcN). Both the physiological hyperinsulinemia and experimental GlcN challenge induced comparable losses of PIP(2) and F-actin. In addition to protecting against the insulin-induced membrane/cytoskeletal abnormality and insulin-resistant state, exogenous PIP(2) corrected the GlcN-induced insult on these parameters. Moreover, in accordance with HBP flux directly weakening PIP(2)/F-actin structure, inhibition of the rate-limiting HBP enzyme (glutamine:fructose-6-phosphate amidotransferase) restored PIP(2)-regulated F-actin structure and insulin responsiveness. Conversely, overexpression of glutamine:fructose-6-phosphate amidotransferase was associated with a loss of detectable plasma membrane PIP(2) and insulin sensitivity. A slight decrease in intracellular ATP resulted from amplifying HBP by hyperinsulinemia and GlcN. However, experimental maintenance of the intracellular ATP pool under both conditions with inosine did not reverse the PIP(2)/F-actin-based insulin-resistant state. Furthermore, less invasive challenges with glucose, in the absence of insulin, also led to PIP(2)/F-actin dysregulation. Accordingly, we suggest that the functionality of cell systems dependent on PIP(2) and/or F-actin status, such as the glucose transport system, can be critically compromised by inappropriate HBP activity.

IL-1beta-mediated innate immunity is amplified in the db/db mouse model of type 2 diabetes.

Chronic inflammation appears to play a critical role in type 2 diabetes and its complications. Here we tested the hypothesis that this inflammatory dysregulation affects the IL-1beta system and has functional consequences in the brain. Diabetic, db/db, and nondiabetic, db/+, mice were administered i.p. LPS, a potent cytokine inducer, at a dose of 100 microg/kg/mouse. db/db mouse innate immune-associated sickness behavior was 14.8, 33, 44.7, and 34% greater than that of db/+ mice at 2, 4, 8, and 12 h, respectively. When a fixed dose of LPS was used (5 microg/mouse), db/db mouse sickness was again enhanced 18.4, 22.2, and 14.5% at 4, 8, and 12 h as compared with db/+ mice. In diabetic mice, peritoneal macrophages produced more IL-1beta in response to LPS, and peritoneal levels of IL-1beta induced by LPS were increased. Importantly, IL-1R antagonist and type 2 IL-1 receptor (IL-1R2) failed to up-regulate in response to LPS in db/db mice. Finally, both peripheral and central administration of IL-1beta, itself, induced sickness in db/db mice that mimicked the effects of peripheral LPS and was significantly greater than that seen in db/+ mice. Taken together, these results indicate that IL-1beta-mediated innate immunity is augmented in db/db mice both at the periphery and in the brain, and the mechanism is due to diabetes-associated loss of IL-1beta counterregulation.