Formaldehyde Exposure Racial Disparities in Southeast Texas.

Formaldehyde (HCHO) exposures during a full year were calculated for different race/ethnicity groups living in Southeast Texas using a chemical transport model tagged to track nine emission categories. Petroleum and industrial emissions were the largest anthropogenic sources of HCHO exposure in Southeast Texas, accounting for 44% of the total HCHO population exposure. Approximately 50% of the HCHO exposures associated with petroleum and industrial sources were directly emitted (primary), while the other 50% formed in the atmosphere (secondary) from precursor emissions of reactive compounds such as ethylene and propylene. Biogenic emissions also formed secondary HCHO that accounted for 11% of the total population-weighted exposure across the study domain. Off-road equipment contributed 3.7% to total population-weighted exposure in Houston, while natural gas combustion contributed 5% in Beaumont. Mobile sources accounted for 3.7% of the total HCHO population exposure, with less than 10% secondary contribution. Exposure disparity patterns changed with the location. Hispanic and Latino residents were exposed to HCHO concentrations +1.75% above average in Houston due to petroleum and industrial sources and natural gas sources. Black and African American residents in Beaumont were exposed to HCHO concentrations +7% above average due to petroleum and industrial sources, off-road equipment, and food cooking. Asian residents in Beaumont were exposed to HCHO concentrations that were +2.5% above average due to HCHO associated with petroleum and industrial sources, off-road vehicles, and food cooking. White residents were exposed to below average HCHO concentrations in all domains because their homes were located further from primary HCHO emission sources. Given the unique features of the exposure disparities in each region, tailored solutions should be developed by local stakeholders. Potential options to consider in the development of those solutions include modifying processes to reduce emissions, installing control equipment to capture emissions, or increasing the distance between industrial sources and residential neighborhoods.

Essential Oils from the Genus Piper Promote Antinociception by Modulating TRP Channels and Anti-Inflammatory Effects in Adult Zebrafish.

The Piper genus, known for its pharmacological potential, comprises 2,263 species primarily found in tropical regions. Despite recent advancements in pain therapies, the demand for more effective and well-tolerated analgesics and anti-inflammatories, particularly for chronic pain, remains. This study assessed the effects of essential oils from Piper caldense, Piper mosenii, and Piper mikanianum on nociceptive behavior induced by formalin and capsaicin, as well as their anti-inflammatory impact induced by carrageenan, using adult zebrafish models. Results indicated non-toxic essential oils with antinociceptive properties in both neurogenic and inflammatory phases of formalin-induced nociception through interaction with the TRPA1 receptor. Additionally, P. mosenii essential oil also blocked the nociceptive effect of capsaicin, a TRPV1 receptor agonist. Furthermore, essential oils from P. caldense and P. mikanianum exhibited significant anti-inflammatory effects by reducing carrageenan-induced abdominal edema. These findings highlight the pharmacological potential of Piper's essential oils as antinociceptive and anti-inflammatory agents.

Survival of formalin intoxication in a 13-year-old Thoroughbred gelding.

BACKGROUND: Formalin intoxication via the gastrointestinal route has not been previously reported in the horse. Whereas ingestion of formalin in humans, although rare, is well documented. Majority of human cases are either accidental, suicidal or homicidal and often lead to fatality, with a reported lethal formaldehyde dose equating to 0.12 - 0.16 g/kg bwt. OBJECTIVES: To describe a single case report of the clinical management of an adult horse referred to a veterinary teaching hospital following accidental administration of 10% formalin via nasogastric tube. METHODS: A 13-year-old Thoroughbred gelding originally presented to the referring veterinarian for colic where 1.8 L of 10% formalin was accidentally administered instead of mineral oil via nasogastric intubation, a potentially lethal dose of formaldehyde (0.12 g/kg bwt). Approximately 20-hours following 10% formalin administration the horse was admitted to the referral hospital with moderate tachycardia, occasional ectopic beats, tacky and hyperaemic mucous membranes, delayed capillary refill time, reduced borborygmi, and pronounced digital pulses. Diagnostic investigations included laboratory blood analysis, urinalysis, electrocardiogram, abdominal ultrasound, palpation per rectum and gastroscopy. RESULTS: Patient assessment found evidence of toxicity to the gastrointestinal tract, hypovolaemia and risk for laminitis. Intensive care included fluid and electrolyte therapy, anti-inflammatories and analgesia, continuous digital cryotherapy, gastro-protectants and other methods of gastrointestinal support. The horse was discharged from hospital on day 14 with no long-term complications and the client-veterinarian relationship was preserved. DISCUSSION: In human cases of ingestion, gastrointestinal injury is typically accompanied by severe metabolic acidosis and multiple organ dysfunction syndrome due to toxicity of other body systems that can contribute to non-survival. Formaldehyde toxicity in the present case predominantly affected the gastrointestinal tract, most likely a direct result of the route of administration. Aside from gastrointestinal injury, primary toxicity of other body systems was not confirmed. To prevent this medical error recurring, the referring veterinary clinic revised their labelling and storage of 10% formalin. CONCLUSION: This is the first report of systemic formalin intoxication in the horse. Following a high dose of 10% formalin (0.12 g/kg bwt formaldehyde) enterally, the horse survived having received intensive supportive care based on human guidelines for ingested formalin.

Mechanisms involved in the antinociceptive and anti-inflammatory effects of xanthotoxin.

Xanthotoxin (XAT) is a natural furanocoumarin clinically used in the treatment of skin diseases such as vitiligo and psoriasis. Recent studies have also investigated its effects on anti-inflammatory, anti-cognitive dysfunction, and anti-amnesia as a guideline for clinic application. However, little is known about its effects on pain relief. Here, we tested the analgesic effects of XAT in serious acute pain and chronic pain models. For acute pain, we used hot-, capsaicin- and formalin-induced paw licking. Nociceptive threshold was measured by mechanical stimuli with von Frey filaments. For chronic pain, we injected complete Freund's adjuvant (CFA) into the mice's plantar surface of the hind paw to induce inflammatory pain. Heat and mechanical hyperalgesia were evaluated by radiant heat and von Frey filament tests, respectively. To investigate the mechanisms underlying the analgesic effect of XAT, we used calcium imaging and western blot to assess transient receptor potential vanilloid 1 (TRPV1) activity and expression in isolated L4-L6 dorsal root ganglion (DRG) neurons. Haematoxylin and eosin (HE) staining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine immune cell recruitment and proinflammatory factor release from skin tissue from paw injection sites. Our results demonstrated that XAT not only reduced acute pain behaviors generated by hot, capsaicin, and formalin but also attenuated CFA-induced heat and mechanical hyperalgesia. The analgesic activity of XAT may be achieved by controlling peripheral inflammation, lowering immune cell infiltration at the site of inflammatory tissue, reducing inflammatory factor production, and therefore inhibiting TRPV1 channel sensitization and expression.

ß-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo.

Inflammation is a complex biological response involving the immune, autonomic, vascular, and somatosensory systems that occurs through the synthesis of inflammatory mediators and pain induction by the activation of nociceptors. Staphylococcus aureus, the main cause of bacteremia, is one of the most common and potent causes of inflammation in public health, with worse clinical outcomes in hospitals. Antioxidant substances have been evaluated as alternative therapeutic analgesics, antioxidants, anti-inflammatory agents, antitumor agents, and bactericides. Among these, we highlight the essential oils of aromatic plants, such as ß-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The objective of this study was to evaluate the biological activities of BCP-DHA association in in vitro and in vivo experimental models of antinociception and inflammation. To determine the anti-inflammatory effects, monocytes isolated from the peripheral blood of adult male volunteers were infected with methicillin-resistant S. aureus and incubated with treatment for cytokine dosage and gene expression analysis. Antinociceptive effects were observed in the three models when comparing the control (saline) and the BCP-DHA treatment groups. For this purpose, the antinociceptive effects were evaluated in animal models using the following tests: acetic acid-induced abdominal writhing, paw edema induced by formalin intraplantar injection, and von Frey hypernociception. There was a significant reduction in the GM-CSF, TNFα, IL-1, IL-6, and IL-12 levels and an increase in IL-10 levels in the BCP-DHA treatment groups, in addition to negative regulation of the expression of the genes involved in the intracellular inflammatory signaling cascade (IL-2, IL-6, IRF7, NLRP3, and TYK2) in all groups receiving treatment, regardless of the presence of infection. Statistically significant results (p < 0.05) were obtained in the acetic acid-induced abdominal writhing test, evaluation of paw edema, evaluation of paw flinching and licking in the formalin intraplantar injection model, and the von Frey hypernociception test. Therefore, BCP and DHA, either administered individually or combined, demonstrate potent anti-inflammatory and antinociceptive effects.

Analysis of antidiabetic, antiulcer and analgesic potential of traditional ethnomedicinal plant Emex spinosa (L.) Campd. from Azad Jammu and Kashmir.

In this research antidiabetic, analgesic and antiulcer potential of traditional ethnomedicinal plant: Emex spinosa (L.) Campd. (Family Polygonaceae) was evaluated by extracting its phytoconstituents using methanol (MeOH) solvent through maceration protocol. The quantitative phytochemical analysis of the extract revealed flavonoids were highest in leaf extract (15.63±0.93 mg/mL) and with (11.5±0.57 mg/mL) in stem. Alkaloids and tanins were also present in the samples in various conc. while saponins were absent. To confirm pharmaceutical potential of plant against ulcer, diabetes and analgesic infirmities, a model experimental animal wistar albino rats (Rattus norvegicus) were used. In antiulcer study, using hot plate method the maximum results were observed with 250 mg/kg in the 2.5 hours of study. The leaf extract showed a 40.41±2.73 latency time and the fruit with a 36.77±2.41, and the stem with a 27.85±3.09, which was comparable to the standard drug Aspirin, i.e., 47.5±0.57. For analysis of antiulcer potential of the plants parts doses of 250 and 500 mg/kg was applied to check the reclamation of ethanol-induced acute ulcer and of Aspirin-induced chronic ulcer of stomach. In order to confirm efficacy of the drug potential of plant following parameters like microscopic evaluation, gastric volume, total acidity, mucosa weight, ulcer index, pH and histopathology of stomach were analyzed. In antidiabetic analysis, in an acute study after a single dose of 500 mg/kg extract after 2hrs the blood glucose levels were 367±51.09958NS, 416±59.79548NS, 437.5±61.96437NS mg/dL for leaf, stem and fruit, respectively. After4hrs 351.75±88.27644NS mg/dl, 448.25±25.64948NS mg/dl, 445.25±27.07205NS mg/dl and after 6hrs 354.5±92.70428NS, 442±24.60691NS, a440±33.16625NS mg/dl, respectively. The analgesic activity was explored by applying hot plate, tail flick and formalin paw licking method. In hot plate method the maximum results were observed with 250mg/kg in the 2.5 hours of study. The leaf extract showed a 40.41±2.73 latency time and the fruit with a 36.77±2.41 and the stem with a 27.85±3.09, which was comparable to the standard drug Aspirin, i.e., 47.5±0.57. The respective plant extracts at 250mg/kg showed a gradual rise in latency time when compared to the control. It was concluded that all three components of E. spinosa perform proved to be significant as potential source of herbal medicines to cure different prevalently occurring diseases. Furthermore, it was confirmed through results analysis that plant t can be used to discover novel drug using dedicated high throughput techniques and ethnopharmacological approaches.

Synthesis, Molecular Docking and Biological Evaluation of N-Substituted Indole Derivatives as Potential Anti-Inflammatory and Antioxidant Agents.

Novel N-substituted Indole derivatives with various hetero-cyclic moieties were synthesized via an ethyl linker in order to obtain highly potent anti-inflammatory and antioxidant agents. The structure of the obtained chemical compounds was determined using IR, 1 H-NMR, and mass spectroscopy. Molecular docking was used to create selective and efficient COX-2 inhibitors from twelve novel indole derivatives (11a-c, 12a-c, 13a-c, and 14a-c). The compounds 13b and 14b had a high interaction energy, which inhibited the COX-2 enzyme. There is a relationship between anti-inflammatory activity and antioxidants, which is also defined by COX-2 inhibition, according to the mechanism of action. The Swiss ADME online programme was used to determine the drug-like properties of synthesized compounds. Two common and reliable methods were adopted to determine the antioxidant effect. In the DPPH assay, compounds 11a, 11b, and 14b, whereas compounds 11b, 13b, and 14b in the reducing power assay, were the most potent as compared with standard ascorbic acid. To evaluate the anti-inflammatory effect at an acute and chronic level, the carrageenan-induced paw edema method along with the formalin-induced inflammation method were used both at low dose and high dose. From the collected results, compounds 13b and 14b were the most potent against acute and chronic inflammation. The results showed that the synthesized compounds are unique as anti-inflammatory and antioxidant agents, and that they could be useful for drug discovery in the future.

LC-MS/MS Quantitation of Formaldehyde-Glutathione Conjugates as Biomarkers of Formaldehyde Exposure and Exposure-Induced Antioxidants: A New Look on an Old Topic.

Humans are continuously exposed to formaldehyde via both endogenous and exogenous sources. Prolonged exposure to formaldehyde is associated with many human diseases, such as lung cancer and leukemia. The goal of this study is to develop biomarkers to measure formaldehyde exposure, which could be used to predict the risk of associated diseases. As glutathione (GSH) is well-known for its crucial role in the detoxification of a wide variety of xenobiotics, including formaldehyde, we rigorously quantitated in this study the conjugates formed when formaldehyde reacted with GSH using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) coupled with an isotope dilution method. The results showed for the first time that (S)-1-(((R)-2-amino-3-(carboxymethylamino)-3-oxopropylthio)methyl)-5-oxopyrrolidine-2-carboxylic acid (PGF) and thioproline-glycine (SPro-Gly) are major metabolites in both nonenzymatic reactions and formaldehyde-exposed human cells. In particular, over 35% of the formaldehyde from external sources was found to convert to SPro-Gly in the exposed cells. Interestingly, data showed that these exposure-induced adducts exhibited good antioxidative properties, which can protect cells from hydrogen peroxide mediated oxidative insult. It is anticipated that the findings of this study could shed light on developing PGF and SPro-Gly as dietary supplements and on the development of noninvasive methods to assess health risks associated with formaldehyde exposure.

Formaldehyde toxicity in age-related neurological dementia.

The primordial small gaseous molecules, such as: NO, CO, H2S and formaldehyde (FA) are present in the brains. Whether FA as well as the other molecules participates in brain functions is unclear. Recently, its pathophysiological functions have been investigated. Notably, under physiological conditions, learning activity induces a transient generation of hippocampal FA, which promotes memory formation by enhancing N-methyl-D-aspartate (NMDA)-currents. However, ageing leads to FA accumulation in brain for the dysregulation of FA metabolism; and excessive FA directly impairs memory by inhibiting NMDA-receptor. Especially, in Alzheimer's disease (AD), amyloid-beta (Aß) accelerates FA accumulation by inactivating alcohol dehydrogenase-5; in turn, FA promotes Aß oligomerization, fibrillation and tau hyperphosphorylation. Hence, there is a vicious circle encompassing Aß assembly and FA generation. Even worse, FA induces Aß deposition in the extracellular space (ECS), which blocks the medicines (dissolved in the interstitial fluid) flowing into the damaged neurons in the deep cortex. However, phototherapy destroys Aß deposits in the ECS and restores ISF flow. Coenzyme Q10, which scavenges FA, was shown to ameliorate Aß-induced AD pathological phenotypes, thus suggesting a causative relation between FA toxicity and AD. These findings suggest that the combination of these two methods is a promising strategy for treating AD.

The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema.

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.

Effect of Cigarette Constituent Messages With Engagement Text on Intention to Quit Smoking Among Adults Who Smoke Cigarettes: A Randomized Clinical Trial.

Importance: The US Food and Drug Administration (FDA) is required to communicate the risks of tobacco constituents to the public. Few studies have addressed how FDA media campaigns can effectively communicate about cigarette smoke constituents. Objective: To examine whether messages about cigarette smoke constituents are effective in reducing smoking intentions and behaviors among adults who smoke. Design, Setting, and Participants: This randomized clinical trial enrolled participants who were aged between 18 and 65 years, were English speakers, were living in the United States, and who smoked at least 100 cigarettes during their lifetime and now smoked every day or some days. Participants received daily messages via email for 15 days. Participants were randomized to 1 of 2 message conditions or a control group and reported their previous-day smoking behaviors daily. Follow-up surveys were conducted on days 16 and 32. Data were collected from June 2017 to April 2018 and analyzed from April to September 2018. Interventions: The 3 groups were (1) constituent plus engagement messages (eg, "Cigarette smoke contains arsenic. This causes heart damage.") that included the FDA as the source and engagement text (eg, "Within 3 months of quitting, your heart and lungs work better. Ready to be tobacco free? You can quit. For free nicotine replacement, call 1-800-QUIT-NOW"); (2) constituent-only messages that did not list the FDA as the source or include engagement text; and (3) a control condition with messages about littering cigarette butts. Main Outcomes and Measures: The primary outcome was the change in quit intentions (range, 1-4, with higher scores indicating stronger intentions) from pretest to day 16. Secondary outcome measures included daily smoking behaviors and quit attempts. Results: A total of 789 participants (mean [SD] age, 43.4 [12.9] years; 483 [61.2%] women; 578 [73.3%] White; 717 [90.9%] non-Hispanic) were included in the study. The mean (SD) quit intention score was 2.5 (0.9) at pretest. Mean (SE) change in quit intention score from pretest to day 16 was 0.19 (0.07) points higher in the constituent plus engagement condition than in the control condition (P = .005) and 0.23 (0.07) points higher in the constituent-only condition compared with the control condition (P = .001). Participant reports of cigarettes smoked, forgone, and butted out were similar across study conditions at baseline and did not differ significantly at days 16 and 32 across study conditions. Viewing more messages was associated with an estimated decrease of 0.15 (SE, 0.01) cigarettes smoked per day per message viewed overall across conditions. Conclusions and Relevance: To our knowledge, this is the first longitudinal test of cigarette constituent campaign messages in a national sample of adults who currently smoke. Messages about cigarette smoke constituents, with or without engagement text and source information, increased participants' intentions to quit, lending support to FDA efforts to educate consumers about such constituents. Trial Registration: ClinicalTrials.gov Identifier: NCT03339206.

Acyclic Triterpenoid Isolated from Alpinia katsumadai Alleviates Formalin-Induced Chronic Mouse Paw Inflammation by Inhibiting the Phosphorylation of ERK and NF-κB.

Chronic and excessive inflammation can destroy host organs and cause inflammatory diseases such as inflammatory bowel disease, asthma, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Alpinia katsumadai seed-derived 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (PHT) using lipopolysaccharide (LPS)-stimulated J774 cells and a formalin-induced chronic paw inflammation mouse model. The in vitro results showed that PHT exhibited no cytotoxicity and decreased LPS-induced NO secretion. Additionally, PHT inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. The quantitative real-time PCR results showed that PHT downregulated the gene expression of the proinflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). PHT inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). In a mouse model, oral administration of 50 mg/kg PHT significantly alleviated both mouse paw thickness and volume. These results indicate that PHT has potential anti-inflammatory effects and should be considered a possible functional material.

Analgesic Effect of Intrathecal Melissa officinalis in the Rat Model of Hot-Water and Formalin-Induced Pain.

Melissa officinalis (MO) is one of the oldest herbal medicines commonly used in traditional medicine, which some studies have investigated for its analgesic effect. This study is an attempt to investigate the effects of intrathecal administration of Melissa officinalis on the pain induced by heat and formalin. In this experimental study, 70 male Wistar rats with an average weight of 270-320 g were randomly divided into five groups: control; sham that received 25 µl of saline through the spinal catheter; and three experimental groups that received 5, 10 or 20 mg/kg M. officinalis via the spinal catheter respectively. Five days after catheterization of the spinal cord from the lumbar region under anesthesia, the effects of Intrathecal administration of M. officinalis on heat- and formalin-induced pain were evaluated. Data were analyzed by using one-way ANOVA. Intrathecal injection of M. officinalis blocked heat-induced pain compared to sham group (p = 0.001). Maximum analgesia was observed 30 min after the injection. Furthermore, intrathecal administration of MO alleviated both acute (p = 0.007) and chronic (p = 0.001) phases of formalin-induced pain. Motor block was not observed in any of the above mentioned groups. The results showed that intrathecal administration of MO could significantly improve hot-water and formalin-induced pain in male Wistar rats.

Illumination with 630 nm Red Light Reduces Oxidative Stress and Restores Memory by Photo-Activating Catalase and Formaldehyde Dehydrogenase in SAMP8 Mice.

AIMS: Pharmacological treatments for Alzheimer's disease (AD) have not resulted in desirable clinical efficacy over 100 years. Hydrogen peroxide (H2O2), a reactive and the most stable compound of reactive oxygen species, contributes to oxidative stress in AD patients. In this study, we designed a medical device to emit red light at 630 ± 15 nm from a light-emitting diode (LED-RL) and investigated whether the LED-RL reduces brain H2O2 levels and improves memory in senescence-accelerated prone 8 mouse (SAMP8) model of age-related dementia. RESULTS: We found that age-associated H2O2 directly inhibited formaldehyde dehydrogenase (FDH). FDH inactivity and semicarbazide-sensitive amine oxidase (SSAO) disorder resulted in endogenous formaldehyde (FA) accumulation. Unexpectedly, excess FA, in turn, caused acetylcholine (Ach) deficiency by inhibiting choline acetyltransferase (ChAT) activity in vitro and in vivo. Interestingly, the 630 nm red light can penetrate the skull and the abdomen with light penetration rates of ∼49% and ∼43%, respectively. Illumination with LED-RL markedly activated both catalase and FDH in the brains, cultured cells, and purified protein solutions, all reduced brain H2O2 and FA levels and restored brain Ach contents. Consequently, LED-RL not only prevented early-stage memory decline but also rescued late-stage memory deficits in SAMP8 mice. INNOVATION: We developed a phototherapeutic device with 630 nm red light, and this LED-RL reduced brain H2O2 levels and reversed age-related memory disorders. CONCLUSIONS: The phototherapy of LED-RL has low photo toxicity and high rate of tissue penetration and noninvasively reverses aging-associated cognitive decline. This finding opens a promising opportunity to translate LED-RL into clinical treatment for patients with dementia. Antioxid. Redox Signal. 00, 000-000.

[False beliefs about vaccines]. / Falsas creencias sobre las vacunas.

Vaccines are an essential tool for the prevention of infectious diseases. However, false ideas and rumours with no scientific foundation about their possible negative effects may dissuade people from being vaccinated, with the consequent risks for the health of the population. The objective of this article is to evaluate the origin and the arguments of some of the most frequent mistaken ideas and rumours about the possible adverse effects of vaccines. Some clearly established adverse effects are presented, as well as false beliefs about various vaccines and potential harm to health. Vaccines, like any drug, can cause adverse effects, but the possible adverse effects of vaccination programs are clearly lower than their individual (vaccinated) and collective benefits (those vaccinated and those who cannot be vaccinated for medical reasons). The possible adverse effects attributable to vaccines should be detected by powerful and well-structured pharmacovigilance systems.

Hormesis and paradoxical effects of pea (Pisum sativum L.) parameters upon exposure to formaldehyde in a wide range of doses.

Formaldehyde is a widespread pollutant of soil near roads including agricultural lands. Non-monotonic changes (hormesis and paradoxical effects) in chlorophyll (Ch) and carotenoid (Car) contents, the lipid peroxidation (LP) rate in plant leaves and growth parameters (GP) of plants can be caused by various pollutants. Hormesis is a biphasic dose-response phenomenon, characterised by low-dose stimulation and high-dose inhibition. The remaining types of non-monotonic responses are classified as paradoxical effects. While most authors who have studied formaldehyde and plants considered gaseous exposure to shoots, the effect of this pollutant in soil solution has been poorly examined. Thus, we studied the non-monotonic changes in Ch and Car contents, LP rate and GP in pea (Pisum sativum L.) upon exposure to formaldehyde in solution, at a wide range of sublethal concentrations from 0.063 × 10-2 to 0.16 g L-1. With formaldehyde exposure, LP and Ch contents had paradoxical effects (triphasic and multiphase changes, accordingly), while Car level did not change and GP exhibited a hormetic response. The date showed that pea parameters display diverse types of non-monotonic responses upon exposure to the same formaldehyde concentrations. High pollutant concentrations (0.08-0.16 g L-1) increased LP and significantly decreased GP (to 2.3-2.5 times compared to the control), while the Ch content was increased. Lower concentrations (<0.08 g L-1) caused a moderate deviation in all parameters from the control (not more than 62%) for hormesis and paradoxical effects.

Effects of Exposure of Formaldehyde to a Rat Model of Atopic Dermatitis Induced by Neonatal Capsaicin Treatment.

Atopic dermatitis is chronically relapsing pruritic eczema and prevails around the world especially in developed countries. Complex interactions between genetic and environmental factors are known to play an important role in the pathophysiology of atopic dermatitis. However, we still lack a detailed picture of the pathogenesis of this disease. Thus, it is of importance to develop appropriate animal models for elucidating the progression of atopic dermatitis. Moreover, investigating the effect of environmental factors such as air pollutants on atopic dermatitis expands understanding of the disease. Here, we describe a method for inducing atopic dermatitis in rats with neonatal capsaicin treatment and a protocol for exposure of a constant concentration of formaldehyde to rats to reveal effects on the development of atopic dermatitis in infantile and adolescent periods. These protocols have been successfully applied to several experiments and can be used for other substances.

Vitamin E Reversed Apoptosis of Cardiomyocytes Induced by Exposure to High Dose Formaldehyde During Mice Pregnancy.

In this study, we investigated the protection effect of Vitamin E (Vit E) on formaldehyde (FA) exposure during pregnancy induced apoptosis of cardiomyocytes, and used an HL-1 cell line to confirmed the findings in vivo.Pregnant mice received different doses of FA (0.5 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 0.1 µg Vit E, or 1.5 mg/kg + 0.1 µg Vit E). TUNEL staining was used to reveal the apoptosis in cardiomyocytes, and SOD, MDA, GSH, Livin, and Caspase-3 in cardiomyocytes were detected by ELISA, RT-PCR, and Western blot. For in vitro study, HL-1 cells were treated with vehicle, 5 µmol/L FA, 25 µmol/L FA, 50 µmol/L FA, 10 mg/L Vit. E, and 50 µmol/L FA+ 10 mg/L Vit E, respectively. CCK-8 assay and flow cytometry were used to evaluate cell vitality and apoptosis. A high dose of FA exposure led to cytotoxicity in both pregnant mice and offspring, as TUNEL staining revealed a significant apoptosis of cardiomyocytes, and the alternation in SOD, GSH, MDA, Livin, and Caspase-3 was found in cardiomyocytes. 0.1 µg Vit. E could reverse high doses of FA exposure induced apoptosis of cardiomyocytes in both pregnant mice and offspring. The in vitro study revealed that FA exposure induced a decrease of cell viability and increased cell apoptosis, as well as oxidative stress in HL-1 cells with alternation in SOD, GSH, MDA, Livin, and Caspase-3.This study revealed a high dose of FA induced oxidative stress and apoptosis of cardiomyocytes in both pregnant mice and offspring, and Vit E supplement during pregnancy reversed the systemic and myocardial toxicity of FA.

Desensitization to chemical and food sensitivities by low-dose immunotherapy ascertained by provocation neutralization is associated with reduced influx of calcium ions into lymphocytes.

Background Food and chemical sensitivities have detrimental effects on health and the quality of life. The natural course of such sensitivities can potentially be altered through various types of allergen-specific immunotherapy, including low-dose immunotherapy. The molecular mechanism by which low-dose immunotherapy causes desensitization has not thus far been elucidated. While resting lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor signaling results in calcium ion influx, predominantly via store-operated calcium channels. We therefore hypothesized that desensitization by low-dose immunotherapy is associated with reduced influx of calcium ions into lymphocytes. The aim of this study was to test this hypothesis. Methods Intracellular lymphocytic calcium ion concentrations were assayed in a total of 47 patients, following incubation with picogram amounts of the test allergens, using a cell-permeable calcium-sensing ratiometric fluorescent dye and fluorescence spectroscopy, both at baseline and following successful provocation neutralization treatment with low-dose immunotherapy. Results Low-dose immunotherapy was associated with a reduction in lymphocytic intracellular calcium ion concentration following treatment of: 23 % for metabisulfite sensitivity (p<0.0004); 12 % for salicylate sensitivity (p<0.01); 23 % for benzoate sensitivity (p<0.01); 30 % for formaldehyde sensitivity (p<0.0001); 16 % for sensitivity to petrol exhaust (p<0.003); 16 % for natural gas sensitivity (p<0.001); 13 % for nickel sensitivity (p<0.05); 30 % for sensitivity to organophosphates (p<0.01); and 24 % for sensitivity to nitrosamines (p<0.05). Conclusions Low-dose immunotherapy may affect baseline levels of intracellular calcium in lymphocytes, supporting the premise that allergens affect cell signaling in immune cells and provocation neutralization immunotherapy helps to promote more normal immune cell signaling.