Exogenous Irritants Research Articles

The effect of the feed supplement “Globigen jump start” on the morphometric parameters of the small intestinal mucosa of piglets

Early weaning of piglets from the sow with a rapid transition from milk to pelleted feed is a common practice in industrial pig farming. To mitigate the feed-related stress in piglets during this period, supplements are introduced into their diet aiming to boost immune response, reduce pathogenic microorganisms in the intestines, and stimulate digestion. This article presents the results of a research on the effect of the feed supplement “Globigen Jump Start”, which contains dried yeast and immunoglobulin-enriched egg powder, on the number of goblet cells and the morphometric parameters of the piglets' small intestine. It was found that the addition of this feed supplement to the piglets' diet significantly increased the height of the duodenal villi by 37.43 % (P > 0.001) by day 14 of the experiment and improved the villus-to-crypt depth ratio, indicating an increase in the surface area and the mucosa's improved ability to absorb nutrients. Additionally, feeding changes also affected the size of the villi in the jejunum and ileum, where a significant increase in size was also observed by day 14, by 12.79 % and 6.6 %, respectively, compared to the control group of piglets. Morphometric studies revealed a trend toward thickening of the muscular layer in both the jejunum and ileum during the first two weeks of consuming pelleted feed with the “Globigen Jump Start” supplement, likely due to changes in diet and the altered feed digestion rate. During the transition to a different type of feed, differences were also noted in the number of goblet cells in the small intestinal mucosa, which produce mucin that protects the body from endogenous and exogenous irritants, microbial adhesion, and aids nutrient transport. In the duodenum of the experimental group of piglets, the number of goblet cells was higher by 3.2 cells on day 14 compared to the control group, and by day 28, this difference decreased to 1.7 cells. A similar trend was observed in the jejunum at both day 14 and day 28, with a significant increase in goblet cell count in the experimental group by 11.6 (P > 0.01) and 13.1 (P > 0.001) compared to control animals. In the ileum of the experimental group, an advantage was also noted. On day 14, the goblet cell count was significantly higher by 6.4 cells (P > 0.05) and by 14.6 (P > 0.001) on day 28 compared to the control group.

Prevalence and causative allergens of contact cheilitis in Thailand.

Cheilitis is an inflammatory condition of the lips. Its causes can be exogenous (irritants, allergens), endogenous (atopic dermatitis, systemic disorders) or unknown. To determine the prevalence of allergic contact cheilitis (ACC), its risk factors, and common allergens in patients with cheilitis at a Thai university-based tertiary care hospital. A retrospective chart review was conducted on patients with cheilitis referred for patch testing between January 2007 and December 2021. Among 5366 patients referred for patch testing, 410 (7.6%) had cheilitis. ACC was diagnosed in 32% of the cheilitis patients. Compared to non-ACC cases, the patients with ACC were more likely to be young and female and have a disease duration of <3 months, no underlying disease and a white-collar job (p-value <0.05). The most common contact allergens were patient's products (73.3%), nickel sulfate (29.8%), potassium dichromate (14.5%), castor oil (14.3%) and benzalkonium chloride (13.0%). Lip cosmetics and toothpastes were major ACC sources. ACC should be considered in cheilitis patients, especially in patients with specific risk factors. Castor oil is an emerging allergen. Patch testing using commercial allergen series and patients' own products is crucial for identifying causative agents. The development of a specific cheilitis series is warranted.

To check contact dermatitis contagion and health hazardous: A review

Skin is the largest organ of our body when it is exposed to exogenous irritants and allergens in 24hours, these noxious agents’ cause immunotoxicity, and Contact dermatitis (CD) is one of them. Here in this review we had checked its types, main causes, Action mechanisms of irritants and allergens, Clinical aspects and its management: diagnostic tests, preventions and treatments of this contagion. There are two types of CD: first is the Irritant contact dermatitis (ICD) and second one is Allergic contact dermatitis (ACD). ICD is exposure of skin by physiological, biological, and chemical toxins resulting into rupturing of stratum corneum and release of cytokines which show inflammatory response. ACD is the interaction of xenobiotics with immune system. It is basically the immunotoxicity by chemicals which is developed by two phases (1) induction and (2) elicitation. Phototoxic and photo allergic CD is developed when CD is due to sunlight exposure. Management of CD is including (1) primary prevention: by avoidance or preventions at different levels (2) secondary prevention: when skin is affected by chemicals then diagnoses is very necessary by Patch test and photo Patch test(3)Tertiary prevention: treatment should be done as soon as possible by steroids and other products.

NLRP3 Inflammasome: Checkpoint Connecting Innate and Adaptive Immunity in Autoimmune Diseases.

Autoimmune diseases are a broad spectrum of human diseases that are characterized by the breakdown of immune tolerance and the production of autoantibodies. Recently, dysfunction of innate and adaptive immunity is considered to be a key step in the initiation and maintenance of autoimmune diseases. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a multimeric protein complex, which can detect exogenous pathogen irritants and endogenous danger signals. The main function of NLRP3 inflammasome is to promote secretion of interleukin (IL)-1β and IL-18, and pyroptosis mediated by caspase-1. Served as a checkpoint in innate and adaptive immunity, aberrant activation and regulation of NLRP3 inflammasome plays an important role in the pathogenesis of autoimmune diseases. This paper reviewed the roles of NLRP3 inflammasome in autoimmune diseases, which shows NLRP3 inflammasome may be a potential target for autoimmune diseases deserved further study.

Role of TRPA1 in Tissue Damage and Kidney Disease.

TRPA1, a nonselective cation channel, is expressed in sensory afferent that innervates peripheral targets. Neuronal TRPA1 can promote tissue repair, remove harmful stimuli and induce protective responses via the release of neuropeptides after the activation of the channel by chemical, exogenous, or endogenous irritants in the injured tissue. However, chronic inflammation after repeated noxious stimuli may result in the development of several diseases. In addition to sensory neurons, TRPA1, activated by inflammatory agents from some non-neuronal cells in the injured area or disease, might promote or protect disease progression. Therefore, TRPA1 works as a molecular sentinel of tissue damage or as an inflammation gatekeeper. Most kidney damage cases are associated with inflammation. In this review, we summarised the role of TRPA1 in neurogenic or non-neurogenic inflammation and in kidney disease, especially the non-neuronal TRPA1. In in vivo animal studies, TRPA1 prevented sepsis-induced or Ang-II-induced and ischemia-reperfusion renal injury by maintaining mitochondrial haemostasis or via the downregulation of macrophage-mediated inflammation, respectively. Renal tubular epithelial TRPA1 acts as an oxidative stress sensor to mediate hypoxia–reoxygenation injury in vitro and ischaemia–reperfusion-induced kidney injury in vivo through MAPKs/NF-kB signalling. Acute kidney injury (AKI) patients with high renal tubular TRPA1 expression had low complete renal function recovery. In renal disease, TPRA1 plays different roles in different cell types accordingly. These findings depict the important role of TRPA1 and warrant further investigation.

Структура, властивості і фізіологічна роль TRPA1-рецепторів

In mammals, the ankyrin ionotropic transient receptor potential type 1 (TRPA1) is the only member of the TRPA receptor gene subfamily. It is defined as a target for damaging and inflammatory effects in peripheral sensory neurons, which implies its functional role in the development of pain and neurogenic inflammation. Experimental studies indicate that calcium permeable non-selective ion receptor channel TRPA1 is activated by a number of exogenous irritant compounds, factors including low temperatures. This review describes the structure, properties, and physiological role of TRPA1 receptors.

Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models.

The Transient Receptor Potential Ankyrin 1 (TRPA1) cation channel expressed on capsaicin-sensitive afferents, immune and endothelial cells is activated by inflammatory mediators and exogenous irritants, e.g., endotoxins, nicotine, crotonaldehyde and acrolein. We investigated its involvement in acute and chronic pulmonary inflammation using Trpa1 gene-deleted (Trpa1−/−) mice. Acute pneumonitis was evoked by intranasal Escherichia coli endotoxin (lipopolysaccharide: LPS) administration, chronic bronchitis by daily cigarette smoke exposure (CSE) for 4 months. Frequency, peak inspiratory/expiratory flows, minute ventilation determined by unrestrained whole-body plethysmography were significantly greater, while tidal volume, inspiratory/expiratory/relaxation times were smaller in Trpa1−/− mice. LPS-induced bronchial hyperreactivity, myeloperoxidase activity, frequency-decrease were significantly greater in Trpa1−/− mice. CSE significantly decreased tidal volume, minute ventilation, peak inspiratory/expiratory flows in wildtypes, but not in Trpa1−/− mice. CSE remarkably increased the mean linear intercept (histopathology), as an emphysema indicator after 2 months in wildtypes, but only after 4 months in Trpa1−/− mice. Semiquantitative histopathological scores were not different between strains in either models. TRPA1 has a complex role in basal airway function regulation and inflammatory mechanisms. It protects against LPS-induced acute pneumonitis and hyperresponsiveness, but is required for CSE-evoked emphysema and respiratory deterioration. Further research is needed to determine TRPA1 as a potential pharmacological target in the lung.

Pulse diagnosis in the Tibetan medical tradition: the experience of objectification of basic principles of pulse diagnosis using a pulse diagnostic device

This article describes the experience of objectification of basic characteristics of pulse waves in pulse diagnosis based on Tibetan medical tradition. A competent therapist &amp;ndash; expert in Tibetan pulse diagnosis can assess functionality of the body (twelve internal organs and three psychophysiological systems) by feeling the pulse in six points of palpation located on the radial arteries of both wrists of the patient. The goal of this research consists in &amp;ldquo;teaching&amp;rdquo; pulse diagnostic device to recognize the diagnostically relevant characteristics of pulse waves. The article represents an attempt of objectification of the fundamentals of pulse diagnosis. Although pulse diagnosis has always been a subjective art of the talented therapist, its basic knowledge can become part of objective science as it is based on the real physical phenomena. The author describes the method of measuring pulse rate using a pulse diagnostic device in the conditions that create certain predictable responses of the body to an exogenous irritant, which in this case contributes to calming the rlung (wind) system. The experiment involved a group of volunteers. The conclusion is made that similar experiments provide material for the analysis of pulse waves acquired under specifically arranged conditions, which promotes the development of software fort the pulse diagnostic device, and proves that the objectification of fundamentals of pulse diagnosis in the Tibetan medicine is possible, although on a limited basis. The novelty is defined by the fact that the research based on the material of Tibetan medical tradition have not been previously conducted. The work consists of the three parts: first part is an extensive introduction that provides records on Buddhist medicine and pulse diagnosis, which help to understand the essence of the experiments; second part is dedicated to the experimental measurements of pulse rate using pulse diagnostic device; and third part represents the conclusions drawn from the conducted experiments.

Dermatitis de contacto alérgica e irritativa en región vulvar. Impacto de los jabones íntimos

La dermatitis de contacto vulvar es un problema común en dermatología y ginecología; afecta de manera importante la salud y la calidad de vida de las mujeres que la padecen. Más del 50% de los casos de prurito vulvar crónico en mujeres adultas puede ser atribuido a sustancias irritantes y alérgenos, entre ellos los denominados jabones íntimos, cuyo uso es cada vez más frecuente. El principal síntoma de la dermatitis es irritación en la región vulvar; puede presentar síntomas como prurito, ardor y dolor. La dermatitis de contacto se produce después de la exposición a irritantes exógenos o alérgenos. Clínicamente son difíciles de diferenciar estas dos entidades; se requiere realizar una adecuada historia clínica, que indague sobre posibles alérgenos, realizar un examen físico completo y una prueba de parche, único método diagnóstico que confirma la dermatitis alérgica por contacto, para realizar un diagnóstico acertado e iniciar un tratamiento adecuado y eliminar el factor desencadenante.

Transient receptor potential ankyrin-1 causes rapid bronchodilation via nonepithelial PGE2.

Transient receptor potential ankyrin-1 (TRPA1) is a ligand-gated cation channel that responds to endogenous and exogenous irritants. TRPA1 is expressed on multiple cell types throughout the lungs, but previous studies have primarily focused on TRPA1 stimulation of airway sensory nerves. We sought to understand the integrated physiological airway response to TRPA1 stimulation. The TRPA1 agonists allyl isothiocyanate (AITC) and cinnamaldehyde (CINN) were tested in sedated, mechanically ventilated guinea pigs in vivo. Reproducible bronchoconstrictions were induced by electrical stimulation of the vagus nerves. Animals were then treated with intravenous AITC or CINN. AITC and CINN were also tested on isolated guinea pig and mouse tracheas and postmortem human trachealis muscle strips in an organ bath. Tissues were contracted with methacholine, histamine, or potassium chloride and then treated with AITC or CINN. Some airways were pretreated with TRPA1 antagonists, the cyclooxygenase inhibitor indomethacin, the EP2 receptor antagonist PF 04418948, or tetrodotoxin. AITC and CINN blocked vagally mediated bronchoconstriction in guinea pigs. Pretreatment with indomethacin completely abolished the airway response to TRPA1 agonists. Similarly, AITC and CINN dose-dependently relaxed precontracted guinea pig, mouse, and human airways in the organ bath. AITC- and CINN-induced airway relaxation required TRPA1, prostaglandins, and PGE2 receptor activation. TRPA1-induced airway relaxation did not require epithelium or tetrodotoxin-sensitive nerves. Finally, AITC blocked airway hyperreactivity in two animal models of allergic asthma. These data demonstrate that stimulation of TRPA1 causes bronchodilation of intact airways and suggest that the TRPA1 pathway is a potential pharmacological target for bronchodilation.

Examination of the demyelination process in mGFAP‐driven conditional transient receptor potential ankyrin 1 (TRPA1) receptor knockout mice

Transient receptor potential ankyrin 1 (TRPA1) receptors are non‐selective cation channels responsive to a variety of exogenous irritants and endogenous stimuli including products of oxidative stress. It is mainly expressed by primary sensory neurons however, expression of TRPA1 by astrocytes and oligodendrocytes has recently been detected in the mouse brain. Genetic deletion of TRPA1 was shown to attenuate cuprizone‐induced oligodendrocyte apoptosis and myelin loss in mice. In the present study we investigated the astrocyte‐specific mGFAP‐driven conditional TRPA1 gene deficient mice in the cuprizone model. Astrocyte‐specific knockout animals were generated by crossbreeding GFAP‐Cre+/− and floxed TRPA1 (TRPA1Fl/Fl) mice. Cuprizone was administered during 6 weeks and demyelination was followed by magnetic resonance imaging (MRI). At the end of the treatment, myelin loss and glial activation were also investigated by histological methods. The results of the MRI showed significantly increased signal intensity in cuprizone‐treated GFAP‐Cre−/− TRPA1Fl/Fl mice compared to GFAP‐Cre+/− TRPA1Fl/− and GFAP‐Cre+/− TRPA1Fl/Fl animals on week 3 and week 4. However, by week 6 of the treatment the difference was not detectable by either the MRI or the histological methods. According to the currently available data, we presume that TRPA1 receptors localized on astrocytes can be activated by reactive oxygen species in response to cuprizone challenge and the consequent release of pro‐inflammatory mediators contributes to the progression of oligodendrocyte apoptosis. However, the global TRPA1 KO mice presented a more attenuated demyelination compared to the conditional KO mice, it could be hypothesized that TRPA1 receptors expressed by other cell types (neurons, oligodendrocytes) in the brain may also participate in the demyelination process.Support or Funding InformationThis research was funded by grants “The role of neuro‐inflammation in neurodegeneration: from molecules to clinics” (EFOP‐3.6.2‐16‐2017‐00008); Hungarian Brain Research Program 2. 2017‐1.2.1‐NKP‐2017‐00002. and the University of Pécs is acknowledged for a support by the 17886‐4/23018/FEKUTSTRAT excellence grant. G.K. was supported by Richter Gedeon Centenárium Foundation.

Investigation of Cuprizone-Induced Demyelination in mGFAP-Driven Conditional Transient Receptor Potential Ankyrin 1 (TRPA1) Receptor Knockout Mice.

Transient receptor potential ankyrin 1 (TRPA1) receptors are non-selective cation channels responsive to a variety of exogenous irritants and endogenous stimuli including products of oxidative stress. It is mainly expressed by primary sensory neurons; however, expression of TRPA1 by astrocytes and oligodendrocytes has recently been detected in the mouse brain. Genetic deletion of TRPA1 was shown to attenuate cuprizone-induced oligodendrocyte apoptosis and myelin loss in mice. In the present study we aimed at investigating mGFAP-Cre conditional TRPA1 knockout mice in the cuprizone model. These animals were generated by crossbreeding GFAP-Cre+/− and floxed TRPA1 (TRPA1Fl/Fl) mice. Cuprizone was administered for 6 weeks and demyelination was followed by magnetic resonance imaging (MRI). At the end of the treatment, demyelination and glial activation was also investigated by histological methods. The results of the MRI showed that demyelination was milder at weeks 3 and 4 in both homozygous (GFAP-Cre+/− TRPA1Fl/Fl) and heterozygous (GFAP-Cre+/− TRPA1Fl/−) conditional knockout animals compared to Cre−/− control mice. However, by week 6 of the treatment the difference was not detectable by either MRI or histological methods. In conclusion, TRPA1 receptors on astrocytes may transiently contribute to the demyelination induced by cuprizone, however, expression and function of TRPA1 receptors by other cells in the brain (oligodendrocytes, microglia, neurons) warrant further investigation.

A Classification System for Peri-implant Diseases and Conditions.

Peri-implant bone levels are influenced by pathologic and nonpathologic conditions. The understanding of peri-implant disease has evolved over the past several decades, and the classification of peri-implantitis has been limited to descriptions of disease progression or those involving soft and/or hard tissues (peri-implant mucositis or peri-implantitis). However, no classification system has been established based on etiology. The objective of this study was to identify various etiologies for peri-implantitis and to establish a classification system based on the pathogenesis. The results indicate that the majority of bone loss was related to biofilm, followed by iatrogenic factors, exogenous irritants, absence of keratinized tissue, and extrinsic pathology. The proposed classification system will allow the clinician to properly diagnose peri-implant diseases in relation to etiology. These conditions may respond differently to applied therapies.

What Causes Eye Pain?

Eye pain is an unpleasant sensory and emotional experience including sensory-discriminative, emotional, cognitive, and behavioral components and supported by distinct, interconnected peripheral and central nervous system elements. Normal or physiological pain results of the stimulation by noxious stimuli of sensory axons of trigeminal ganglion (TG) neurons innervating the eye. These are functionally heterogeneous. Mechano-nociceptors are only excited by noxious mechanical forces. Polymodal nociceptors also respond to heat, exogenous irritants, and endogenous inflammatory mediators, whereas cold thermoreceptors detect moderate temperature changes. Their distinct sensitivity to stimulating forces is determined by the expression of specific classes of ion channels: Piezo2 for mechanical forces, TRPV1 and TRPA1 for heat and chemical agents, and TRPM8 for cold. Pricking pain is evoked by mechano-nociceptors, while polymodal nociceptors are responsible of burning and stinging eye pain; sensations of dryness appear to be mainly evoked by cold thermoreceptors. Mediators released by local inflammation, increase the excitability of eye polymodal nociceptors causing their sensitization and the augmented pain sensations. During chronic inflammation, additional, long-lasting changes in the expression and function of stimulus-transducing and voltage-sensitive ion channels develop, thereby altering polymodal terminal’s excitability and evoking chronic inflammatory pain. When trauma, infections, or metabolic processes directly damage eye nerve terminals, these display aberrant impulse firing due to an abnormal expression of transducing and excitability-modulating ion channels. This malfunction evokes ‘neuropathic pain’ which may also result from abnormal function of higher brain structures where ocular TG neurons project. Eye diseases or ocular surface surgery cause different levels of inflammation and/or nerve injury, which in turn activate sensory fibers of the eye in a variable degree. When inflammation dominates (allergic or actinic kerato-conjunctivitis), polymodal nociceptors are primarily stimulated and sensitized, causing pain. In uncomplicated photorefractive surgery and moderate dry eye, cold thermoreceptors appear to be mainly affected, evoking predominant sensations of unpleasant dryness.

Vulvar contact dermatitis

Contact dermatitis is a common problem in the world of dermatology as well as women’s health, where vulvar irritation is a frequent complaint among women. It occurs following exposure to exogenous irritants (irritant contact dermatitis) or allergens (allergic contact dermatitis), and can present in acute, subacute, or chronic forms. While vulvar pruritus and pain can be seen in a number of different conditions, contact dermatitis is one of the most common causes encountered in clinical practice, and its effects on patient quality of life can be dramatic. With a thorough history and a complete physical exam, this prevalent condition can be diagnosed and addressed. Treatment is aimed at identifying and eliminating the underlying cause, restoring the damaged epithelial barrier, and calming the inflammation. Although numerous options are available for addressing the itch and pain, the only true ”cure” for contact dermatitis is to avoid the responsible exposures.

The Molecular Basis for Species-specific Activation of Human TRPA1 Protein by Protons Involves Poorly Conserved Residues within Transmembrane Domains 5 and 6

The surveillance of acid-base homeostasis is concerted by diverse mechanisms, including an activation of sensory afferents. Proton-evoked activation of rodent sensory neurons is mainly mediated by the capsaicin receptor TRPV1 and acid-sensing ion channels. In this study, we demonstrate that extracellular acidosis activates and sensitizes the human irritant receptor TRPA1 (hTRPA1). Proton-evoked membrane currents and calcium influx through hTRPA1 occurred at physiological acidic pH values, were concentration-dependent, and were blocked by the selective TRPA1 antagonist HC030031. Both rodent and rhesus monkey TRPA1 failed to respond to extracellular acidosis, and protons even inhibited rodent TRPA1. Accordingly, mouse dorsal root ganglion neurons lacking TRPV1 only responded to protons when hTRPA1 was expressed heterologously. This species-specific activation of hTRPA1 by protons was reversed in both mouse and rhesus monkey TRPA1 by exchange of distinct residues within transmembrane domains 5 and 6. Furthermore, protons seem to interact with an extracellular interaction site to gate TRPA1 and not via a modification of intracellular N-terminal cysteines known as important interaction sites for electrophilic TRPA1 agonists. Our data suggest that hTRPA1 acts as a sensor for extracellular acidosis in human sensory neurons and should thus be taken into account as a yet unrecognized transduction molecule for proton-evoked pain and inflammation. The species specificity of this property is unique among known endogenous TRPA1 agonists, possibly indicating that evolutionary pressure enforced TRPA1 to inherit the role as an acid sensor in human sensory neurons.

Pathophysiologie, Diagnostik und Therapie von chronischem Husten: Neuronale Reflexe und Antitussiva

Cough is the number one symptom for patients to visit a physician worldwide. It is an important neuronal reflex which serves to protect the airways from inhaled exogenous microorganisms, thermal and chemical irritants. Moreover, it prevents the airways from mucus retention.The cough reflex is initiated by activation of different cough receptors. These cough receptors can be divided into three groups according to their electrophysiological properties: into the two Aδ-fiber types "rapid-adapting mechanoreceptor" (RAR) and "slow-adapting mechanoreceptor" (SAR), and the C-fiber receptor.The stimulus is detected by cough receptors which conduct the signal to the cerebral cough centre via vagal-sensory neurons. The cough itself is mediated by efferent motoneurons. Hence the cough reflex consists of 5 functionally sequential parts 1: the cough receptors 2, the primary afferent fibres of the N. vagus 345, N. trigeminus and N. glossopharyngeus 1, the cough centre in the medulla oblongata (N. tractus solitarius) 678, the afferent fibres of the N. phrenicus, spinal nerve and N. laryngeus recurrens, as well as the diaphragm and the abdominal, intercostal and laryngeal muscles. The cough receptors are mainly located in the larynx, trachea and main bronchi 2.The event of coughing can be divided into four subsequent parts: After the first phase of fast inspiration with an opened glottis, there is compression with a closed glottis and increasing tracheal pressure, acceleration and ultimately maximum expiration with an opened glottis 9. According to its characteristics, cough can be split into two distinct types, "aspiration cough", which is loud and involuntary, and "urge-to-cough sensation", which describes an irritant, scratchy, and controlled cough of slowly increasing intensity 10.Acute cough mostly develops because of infection of the respiratory system 111213 and ends spontaneously after 4 weeks. In contrast to this, bacterial infection with pathogens like Adenovirus, Bordetella pertussis and Mycoplasms can last up to 8 weeks 121314. In additional to the division of cough according to its cause, it can also be differentiated according to its manner: dry and mucus-producing cough.With this review we want to give an overview of neuronal processes and mechanisms, as well as diagnostics of and therapy for chronic cough. Thereby the focus is also placed on the efficiency of already established and potential future antitussive agents.

Irritant Contact Dermatitis due to “Kajal”

A five-mo-old baby was referred to the authors with hypopigmentation at both lower lid margins. There was history of “Kajal” application for the first time which was immediately followed by redness and itching over the lids. Three days later there was post-inflammatory hypopigmentation at both the lid margins (Fig. 1). Hewas diagnosed to have Irritant contact dermatitis to “Kajal” with post—inflammatory hypopigmentation. The parents were advised against Kajal application in future. Irritant contact dermatitis is more frequent in children, particularly during the early years of life caused by a direct local cytotoxic effect of an irritant on the cells of the epidermis, with a subsequent inflammatory response in the dermis. It can result from prolonged or repetitive contact with various substances that most commonly include saliva and the exogenous irritants like citrus juices, bubble bath, detergents, abrasive materials, strong soaps, and proprietary medications. It manifests with redness, itching, swelling, blistering and scaling of the damaged area. The diagnosis is established on the clinical appearance of dermatitis at a site sufficiently exposed to a known cutaneous irritant. It should be excluded from allergic contact dermatitis which is due to delayed hypersensitivity reaction. The definitive treatment consists of identification and removal of the causal agent. Application of “Kajal/surma” is a common practice in Indian families. It has been claimed to keep the eyes cool and clean, improve vision and strengthen the eyes. It is also said to ward off an ‘evil eye. Most commercially produced ‘kajal’ contain high levels of lead. Studies have revealed that ‘Kajal’ comprises of galena (PbS), minium (Pb3O4), amorphous carbon, magnetite (Fe3O4), and zincite (ZnO). Prolonged application may cause excessive lead storage in the body resulting in various hematological and CNS side effects. In addition it can cause trauma and infection to the eyes. Although concerns about its safety have been raised, its use in pediatric age is very prevalent even today. The above case emphasis the need for the health care providers to educate the parents and grandparents regarding the various adverse effects associated with “kajal” application. Fig. 1 Clinical photograph of the child showing dermatitic changes of lower lid margins

Helicobacter pylori infection and antioxidants can modulate the genotoxic effects of heterocyclic amines in gastric mucosa cells

Helicobacter pylori (H. pylori) infection plays an important role in gastric carcinogenesis. This bacterium may induce cancer transformation and change the susceptibility of gastric mucosa cells to various exogenous dietary irritants. The aim of the study was to evaluate the influence of H. pylori infection on the reaction of the stomach cells to a genotoxic effect of heterocyclic amines (HCAs). These well-known mutagens are formed during cooking of protein-rich foods, primarily meat. Taking into account that persons consuming a mixed-western diet are exposed to these compound nearly an entire lifetime and more than half of human population is infected with H. pylori, it is important to assess the combined effect of H. pylori infection and HCAs in the context of DNA damage in gastric mucosa cells, which is a prerequisite to cancer transformation. We employed 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) because these substances are present in a great amount in cooked and fried meat. Using alkaline comet assay, we showed that the extent of the DNA damage induced by HCAs was significantly higher in H. pylori infected gastric mucosa cells than in non-infected counterparts. We did not observed any difference in the efficiency of repair of DNA lesions induced by HCAs in both type of cells. Vitamin C reduced the genotoxic effects of HCAs in H. pylori infected and non-infected gastric mucosa cells. Melatonin more effectively decreased DNA damage caused by HCAs in H. pylori infected gastric mucosa cells as compared with control. Our results suggest that H. pylori infection may influence the susceptibility of gastric mucosa cells to HCAs and dietary antioxidative substances, including vitamin C and melatonin may inhibit the genotoxic effects of HCAs on gastric mucosa cells and may reduce the risk of carcinogenesis caused by food borne mutagens and H. pylori infection.

Roles of TRPA1 in Pain Pathophysiology and Implications for the Development of a New Class of Analgesic Drugs

The Transient Receptor Potential A1 (TRPA1) ion channel has evolved in animals to respond to signals from a variety of sensory stimuli. Many structural determinants of its multimodal activation have been identified to date. TRPA1 activities include responses to exogenous chemical irritants, responses to endogenous inflammatory mediators, zinc, voltage, temperature or stretch and subtle yet critical modulation by calcium ions. TRPA1 has emerged as an important target for several types of pain and inflammatory conditions because of its limited expression profile and its demonstrated roles in mediating different types of pain and sensitization of peripheral sensory afferents. Despite observed species differences in channel pharmacology, recent genetic evidence in human brings some hope that preclinical efficacy in disease models will translate to patient condition. During the past decade, various groups have investigated the development of a new class of analgesic drugs or anti-tussive agents aimed at blocking TRPA1 activity in primary sensory afferents. Several companies are advancing toward clinical proof of concept studies. This review aims to summarize key advances in the understanding of TRPA1 with regard to its roles and implications for patient conditions.