Integrated approaches to prevent exposure risks related to latex-derived products.

Natural rubber latex is a widely used industrial raw material to produce many consumer and commercial products. Chronic exposures to latex allergenic proteins residual in the finished products can promote hypersensitive immune responses, which affects millions of workers and the general public worldwide. Research has shown the average prevalence of latex allergy worldwide remains approximately 10% among healthcare workers, 7% among susceptible patients, and 4% among general population. Although most effective in preventing latex allergy, completely avoiding contact to latex-derived products is extremely challenging, given the fact that millions of products possibly contain latex, but few are regulated and properly labeled. Due to the difficulty to assure a product completely absent of latex allergens, the United States Food and Drug Administration has recommended to stop using labels like "latex-free" or "does not contain latex." Here we evaluate published data, industrial standards and regulations, identify possible countermeasures, and propose an integrated strategy, including some more practicable approaches (e.g., education/training, product labeling, the use of proper personal protective equipment, occupational selection, and searchable product database) and novel medical treatments (e.g., immunotherapy) to help decreasing latex allergy prevalence.

High-frequency electrical stimulation (HFES) Data Lean and Obese Zucker Rat Soleus Muscle: Regulation of p70S6kinase Associated Proteins.

Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the AKT, GSK3beta, mTor, p70s6K, Pten, and Shp2 proteins in the lean and obese (fa/fa) Zucker rat soleus muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al., 2009a, 2009b; Tullgren et al., 1991) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017a, 2017b; Rice et al., 2017a, 2017b) [4-7].

Diabetic Zucker rat Tibialis anterior muscle high-frequency electrical stimulation (HFES) data: Regulation of MAPKs associated proteins.

Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK 1/2, p38, and JNK in the lean and obese (fa/fa) Zucker rat tibialus anterior (TA) muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al., 2009, Katta et al., 2009, Tullgren et al., 1991) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017, Rice et al., 2017, Rice et al., 2017, Rice et al., 2017) [4-7].

Lean and Obese Zucker Rat Extensor Digitorum Longus Muscle high-frequency electrical stimulation (HFES) Data: Regulation of MAPKs Associated Proteins.

Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK 1/2, p38, and JNK in the lean and obese (fa/fa) Zucker rat extensor digitorum longus (EDL) muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our (Katta et al., 2009a, 2009b, 2008) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017a, 2017b; Rice et al., 2017a, 2017b) [4-7].

High-frequency electrical stimulation (HFES) data lean and obese Zucker rat tibialis anterior muscle: Regulation of glycogen synthase kinase 3 beta (GSK3B) associated proteins.

Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the AMPK, GSK3beta, and Shp2 in the lean and obese (fa/fa) Zucker rat tibialis anterior (TA) muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al., 2009; Katta et al., 2009; Tullgren et al., 1991) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017; Rice et al., 2017; Rice et al., 2017; Rice et al., 2017) [4-7].

Lean and Obese Zucker Rat Extensor Digitorum Longus Muscle high-frequency electrical stimulation (HFES) Data: Regulation of p70S6kinase Associated Proteins.

Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the AKT, GSK3beta, mTor, p70s6K, Pten, and Shp2 in the lean and obese (fa/fa) Zucker rat Extensor Digitorum Longus (EDL) muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al., 2009a, 2009b; Tullgren et al., 1991) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017a, 2017b; Rice et al., 2017a, 2017b) [4-7].

Protective Effects of Cerium Oxide Nanoparticles on MC3T3-E1 Osteoblastic Cells Exposed to X-Ray Irradiation.

BACKGROUND/AIMS: Exposure to ionizing radiation can result in bone damage, including decreased osteocyte number and suppressed osteoblastic activity. However, molecular mechanisms remain to be elucidated, and effective prevention strategies are still limited. This study was to investigate whether cerium oxide nanoparticles (CeO2 NP) can protect MC3T3-E1 osteoblast-like cells from damaging effects of X-ray irradiation, and to study the underpinning mechanism(s). METHODS: MC3T3-E1, a osteoblast-like cell line, was exposed to X-ray irradiation and treated with different concentration of CeO2 nanoparticles. The micronucleus frequency was counted under a fluorescence microscope. Cell viability was evaluated using MTT assay. The effects of irradiation and CeO2 nanoparticles on alkaline phosphatase activity and MC3T3-E1 mineralization were further assayed. RESULTS: We found that the ratio of micronuclei to binuclei was dose-dependently increased with X-ray irradiation (from 2 to 6 Gy), but diminished with the increased concentration of CeO2 NP treatment (from 50 to 100 nM). Exposure to X-rays (6 Gy) decreased cell viability, differentiation and the mineralization, but CeO2 NP treatment (100 nM) attenuated the deteriorative effects of irradiation. Both intracellular reactive oxygen species (ROS) production and extracellular H2O2 concentration were increased after X-ray irradiation, but reduced following CeO2 NP treatment. Similar to irradiation, exposure to H2O2 (10 µM) elevated the frequency of micronuclei and diminished cell viability and mineralization, while these changes were ameliorated following CeO2 NP treatment. CONCLUSIONS: Taken together, our findings suggest that CeO2 nanoparticles exhibit astonishing protective effects on irradiation-induced osteoradionecrosis in MC3T3-E1 cells, and the protective effects appear to be mediated, at least partially, by reducing oxidative stress.

Current prevalence rate of latex allergy: Why it remains a problem?

OBJECTIVES: This article aims to review the current prevalence rate of latex allergy among healthcare workers, susceptible patients, and the general public, and to investigate why latex is still a ubiquitous occupational health hazard. METHODS: Scientific publications on PubMed, particularly those published within the last five years, and current regulations from agencies such as Food and Drug Administration (FDA) were reviewed. Consumer and commercial products that may contain latex were also surveyed. RESULTS: Approximately 12 million tons of natural rubber latex is produced annually and is widely used to manufacture millions of consumer and commercial products. Only limited number of latex-derived products have been approved and regulated by government agencies, such as FDA, whereas the majority of finished products do not label whether they contain latex. Owing to millions of unidentifiable products containing latex and many routes for exposure to latex, preventing contact with latex allergens and reducing the prevalence of latex allergy are more difficult than expected. Reported data suggest that the average prevalence of latex allergy worldwide remains 9.7%, 7.2%, and 4.3% among healthcare workers, susceptible patients, and general population, respectively. CONCLUSIONS: Latex-derived products are ubiquitous, and latex allergy remains a highly prevalent health risk in many occupations and to the general population. Developing alternative materials and increasing the ability to identify and label latex-derived products will be practicable approaches to effectively control the health risks associated with latex.

Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKß/AMPK/ACC Pathway.

BACKGROUND/AIMS: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms. METHODS: High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca(2+)/CaM-dependent protein kinase kinase ß (CaMKKß) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated. RESULTS: Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKß/AMPK/ACC pathway. CONCLUSION: These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKß/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.

Acetaminophen attenuates glomerulosclerosis in obese Zucker rats via reactive oxygen species/p38MAPK signaling pathways.

Focal segmental glomerulosclerosis is a critical pathological lesion in metabolic syndrome-associated kidney disease that, if allowed to proceed unchecked, can lead to renal failure. However, the exact mechanisms underlying glomerulosclerosis remain unclear, and effective prevention strategies against glomerulosclerosis are currently limited. Herein, we demonstrate that chronic low-dose ingestion of acetaminophen (30 mg/kg/day for 6 months) attenuates proteinuria, glomerulosclerosis, podocyte injury, and inflammation in the obese Zucker rat model of metabolic syndrome. Moreover, acetaminophen treatment attenuated renal fibrosis and the expression of profibrotic factors (fibronectin, connective tissue growth factor, transforming growth factor ß), reduced inflammatory cell infiltration into the glomeruli, and decreased the expression of monocyte chemoattractant protein, glutathione (GSH) reductase, and nuclear factor erythroid 2-related factor 2, but increased the level of GSH synthetase in obese animals. Further in vivo and in vitro studies using human renal mesangial cells exposed to high glucose or hydrogen peroxide suggested that the renoprotective effects of acetaminophen are characterized by diminished renal oxidative stress and p38MAPK hyperphosphorylation.

Environmental mercury and its toxic effects.

Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects.

Acetaminophen attenuates obesity-related renal injury through ER-mediated stress mechanisms.

BACKGROUND/AIMS: Obesity is an independent risk factor for the development of kidney disease. The purpose of this study was to determine how obesity may contribute to renal damage and whether acetaminophen ingestion can diminish obesity-associated renal cell injury in the obese Zucker rat model. METHODS: Male obese Zucker rats (4 weeks old, n=6) were treated with acetaminophen (30 mg / kg body weight / day) for 26 weeks. Age matched obese control (OC), obese vehicle (OV, 0.073 mL DMSO/kg/d), and lean Zucker rats (LC) were used to determine the effects of treatment and obesity. RESULTS: Compared to lean control rats, renal lipid deposition, expression of the endoplasmic reticulum (ER) stress protein GRP78 and activation of the ER stress-related eIF2α-ATF4-CHOP, caspase 12, and JNK-MAPK signaling pathways were increased in the obese control and obese vehicle rats. These alterations were associated with the elevated renal cell apoptosis and urinary albumin excretion. Acetaminophen treatment decreased renal lipid deposition, ER-stress related signaling, apoptosis and albuminuria. CONCLUSION: These data suggest that the protective effects of low dose acetaminophen on renal injury are mediated, at least in part, through attenuation of ER stress.

Metabolic syndrome-induced tubulointerstitial injury: role of oxidative stress and preventive effects of acetaminophen.

The prevalence of metabolic syndrome persistently increases and affects over 30% of U.S. adults. To study how metabolic syndrome may induce tubulointerstitial injury and whether acetaminophen has renal-protective properties, 4-week-old obese Zucker rats were randomly assigned into three groups, control (OC), vehicle dimethyl sulfoxide (OV), and acetaminophen treatment (30 mg/kg/day for 26 weeks), and lean Zucker rats served as healthy controls. Significant tubulointerstitial injuries were observed in both OC and OV animals, evidenced by increased tubular cell death, tubular atrophy/dilation, inflammatory cell infiltration, and fibrosis. These tubulointerstitial alterations were significantly reduced by treatment with a chronic but low dose of acetaminophen, which acted to diminish NADPH oxidase isoforms Nox2 and Nox4 and decrease tubulointerstitial oxidative stress (reduced tissue superoxide and macromolecular oxidation). Decreased oxidative stress by acetaminophen was paralleled by the reduction of tubular proapoptotic signaling (diminished Bax/Bcl-2 ratio and caspase 3 activation) and the alleviation of tubular epithelial-to-mesenchymal transition (decreased transforming growth factor ß, connective tissue growth factor, α-smooth muscle actin, and laminin). These data suggest that increased oxidative stress plays a critical role in mediating metabolic syndrome-induced tubulointerstitial injury and provide the first evidence suggesting that acetaminophen may be of therapeutic benefit for the prevention of tubulointerstitial injury.

Regulation of contractile proteins and protein translational signaling in disused muscle.

BACKGROUND/AIMS: Muscle disuse can lead to muscle atrophy and impaired skeletal muscle function. How skeletal muscle modulates protein translational signaling in response to prolonged muscle disuse is not well understood. Using the hindlimb unloading (HU) model of muscle atrophy we examined how hindlimb unweighting affects protein translational signaling, including the activation of Akt/mTOR/p70S6K/S6 signaling and the inhibitory association of 4EBP1 with translation initiation factor eIF4E. METHODS: Male F344BN rats were randomized into baseline control, or subjected to HU for 3, 7 or 14 days. Body weight, gastrocnemius muscle, and individual myofiber cross-sectional area were measured to evaluate the degree of muscle atrophy. The amounts of myosin and related muscle contractile proteins were assessed using SDS-PAGE and immunoblotting. Microarray analysis was used to evaluate changes in the mRNA expression of muscle contractile proteins. Total and phosphorylated proteins of Akt/mTOR/p70S6K/S6 pathway were determined via immunoblotting, while the association of 4EBP1 with eIF4E was detected via co-immunoprecipitation. RESULTS: Unloading for 3 days significantly reduced cytosolic myosin content and was associated with increased binding of 4EBP1 to eIF4E, while prolonged unloading (14 days) was associated with the activation of Akt/mTOR/p70S6K/S6 signaling, decreased binding of 4EBP1 to eIF4E, increased cytosolic myosin and elevations in myofibrillar mRNA levels. CONCLUSION: Taken together, these data suggest that prolonged muscle disuse induces a biphasic translational signaling response that is associated with diminished and then increased muscle contractile protein expression.

Diminished muscle growth in the obese Zucker rat following overload is associated with hyperphosphorylation of AMPK and dsRNA-dependent protein kinase.

Previous data have suggested that insulin-resistant skeletal muscle may exhibit a diminished ability to undergo hypertrophy and that this result may be mediated, at least in part, from decrements in mammalian target of rapamycin (mTOR) signaling (Katta A, Kundla S, Kakarla SK, Wu M, Fannin J, Paturi S, Liu H, Addagarla HS, Blough ER. Am J Physiol Regul Integr Comp Physiol 299: R1666-R1675, 2010). Herein, we attempt to extend these observations by determining if this attenuation in muscle growth is associated with alterations in AMP-activated protein kinase (AMPK) signaling, an upstream mediator of mTOR, and changes in the activation of dsRNA-dependent protein kinase (PKR), which functions as an inhibitor of protein synthesis and potential mediator of protein degradation. Compared with that observed in lean Zucker (LZ) rats, the phosphorylation of AMPKα at Thr172 was higher after 3 wk of overload in the insulin-resistant obese Zucker (OZ) soleus (P < 0.05). This change in AMPKα phosphorylation was accompanied by increases in the amount of phosphorylated PKR (Thr446), elevations in the PKR-dependent phosphorylation of eukaryotic initiation factor (eIF)-2α (Ser51), augmented p38 MAP kinase (Thr180/Tyr182) phosphorylation, and increases in the amount of protein ubiquitination (P < 0.05). Taken together, these results suggest that the diminished hypertrophic response we observe in the OZ rat may be mediated, at least in part, by the hyperactivation of AMPK- and PKR-related signaling.

Regulation of iron-related molecules in the rat hippocampus: sex- and age-associated differences.

Iron accumulation, especially that of free oxidized ferrous iron, has been shown to induce tissue oxidative damage and contribute to brain aging and the development of neurodegenerative disease. Here we examine whether sex and advanced age affect the expression of iron-related molecules that participate in regulating free iron levels (heme oxygenase 1 (HO1), iron-regulatory protein 1 (IRP1), and ferritin heavy chain (FTH)) and whether changes in the expression of these molecules are associated with differences in the expression of alpha-synuclein (ASN) which is thought to be a critical regulator in the pathogenesis of neurodegeneration. Using a well-established aging animal model, we demonstrate that the expression of HO1, FTH, and IRP1 mRNAs is higher in the female hippocampus than that observed in male Fischer 344/NNiaHSD x Brown Norway/BiNia (F344BN) rats, regardless of age group. Consistent with these sex-associated alterations in iron-related regulators, the expression of ASN mRNA and protein in the female hippocampus was lower than that found in male rats. These results suggest a sex-dependent difference in regulating the expression of molecules involved in iron metabolism and neurodegeneration. A similar finding in humans, if present, may help to shed light on why sex may affect the incidence of neurodegenerative disorders.

Acetaminophen: beyond pain and Fever-relieving.

Acetaminophen, also known as APAP or paracetamol, is one of the most widely used analgesics (pain reliever) and antipyretics (fever reducer). According to the U.S. Food and Drug Administration, currently there are 235 approved prescription and over-the-counter drug products containing acetaminophen as an active ingredient. When used as directed, acetaminophen is very safe and effective; however when taken in excess or ingested with alcohol hepatotoxicity and irreversible liver damage can arise. In addition to well known use pain relief and fever reduction, recent laboratory and pre-clinical studies have demonstrated that acetaminophen may also have beneficial effects on blood glucose levels, skeletal muscle function, and potential use as cardioprotective and neuroprotective agents. Extensive laboratory and pre-clinical studies have revealed that these off-label applications may be derived from the ability of acetaminophen to function as an antioxidant. Herein, we will highlight these novel applications of acetaminophen, and attempt, where possible, to highlight how these findings may lead to new directions of inquiry and clinical relevance of other disorders.

Deferasirox protects against iron-induced hepatic injury in Mongolian gerbil.

Iron overload is associated with an increased risk of liver complications including fibrosis, cirrhosis, and hepatocellular carcinoma. Deferasirox is a new oral chelator with high iron-binding potency and selectivity. Here we investigate the ability of deferasirox to remove excessive hepatic iron and prevent iron-induced hepatic injury. Adult male Mongolian gerbils were divided into 3 groups (n=5/group)-control, iron overload (100 mg iron-dextran/kg body weight/5 days; intraperitoneal for 10 weeks), and iron overload followed by deferasirox treatment (100 mg deferasirox/kg body weight/d; pulse oral for 1 or 3 months). Compared with the nontreated iron overload group, deferasirox reduced hepatic iron concentration by 44% after 3 months of treatment (P<0.05). Histological analysis of hepatic tissue from the iron overloaded group detected frequent iron deposition, evidence of hepatic damage, and an accumulation of lipid vacuoles. Iron deposition was significantly diminished with deferasirox treatment, and no evidence of lipid accumulation was observed. Immunoblotting demonstrated that iron overload caused approximately 2-fold increase in hepatic ferritin expression (P<0.05), which was 48% lower after 3 months of deferasirox treatment (P<0.05). Deferasirox treatment also was associated with reduced hepatic protein oxidation, superoxide abundance, and cell death. The percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells in the deferasirox-treated livers was 41% lower than that of iron overloaded group (P<0.05). Similarly, an iron-related increase in the expression of Bax/Bcl2, Bad, and caspase-3 were significantly lower after deferasirox treatment. These findings suggest that deferasirox may confer protection against iron-induced hepatic toxicity.

Iron-induced cardiac damage: role of apoptosis and deferasirox intervention.

Excess cardiac iron levels are associated with cardiac damage and can result in increased morbidity and mortality. Here, we hypothesize that elevations in tissue iron can activate caspase-dependent signaling, which leads to increased cardiac apoptosis and fibrosis, and that these alterations can be attenuated by iron chelation. Using an iron-overloaded gerbil model, we show that increased cardiac iron is associated with reduced activation of Akt (Ser473 and Thr308), diminished phosphorylation of the proapoptotic regulator Bad (Ser136), and an increased Bax/Bcl-2 ratio. These iron-overload-induced alterations in Akt/Bad phosphorylation and Bax/Bcl-2 ratio were coupled with increased activation of the downstream caspase-9 (40/38- and 17-kDa fragments) and apoptosis executioner caspase-3 (19- and 17-kDa fragments), which were accompanied by evidence of elevated cytoskeletal α-fodrin cleavage (150- and 120-kDa fragments), discontinuity of myocardial membrane dystrophin immunoreactivity, increases in the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells (nucleic DNA fragmentation), and cardiac fibrosis. We demonstrate that the administration of deferasirox, a tridentate iron chelator, is associated with diminished tissue iron deposition, attenuated activation of caspases, reduced α-fodrin cleavage, improved membrane integrity, decreased TUNEL reactivity, and attenuated cardiac fibrosis. These results suggest that the activation of caspase-dependent signaling may play a role in the development of iron-induced cardiac apoptosis and fibrosis, and deferasirox, via a reduction in cardiac tissue iron levels, may be useful for decreasing the extent of iron-induced cardiac damage.

Effect of aging on cellular mechanotransduction.

Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, respiratory systems and skin.