External Irritation Research Articles

Immune Cells and Molecular Networks in Experimentally Induced Pulpitis

Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-β, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell–enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria.

Cholesterol Crystal Deposition in Basal Cell Carcinoma: An Investigation of 4 Cases

Cholesterol crystals are a primary cause of cholesterol embolism if they appear in vessels. Various papers have reported the involvement of cholesterol crystal deposition in cutaneous diseases such as xanthoma. However, no cases of cholesterol crystal involvement in cutaneous cancer have been reported. We report four cases of basal cell carcinoma with cholesterol crystal deposition, and discuss the mechanism(s) of the condition. Disease duration, anatomical site, histopathological features, and serum lipid profiles were investigated. The median disease duration was 3.5 years, and the sites of the lesions were the scrotum (one patient) and the nose (three patients). Histopathologically, there was necrotized tissue around the clefts. In addition, we detected frequent apoptotic cells around the cholesterol clefts in two of the patients by using the terminal deoxynucleotidyl transferase dUTP nick-end labeling method. Serum lipid levels were slightly elevated in two of the patients. In conclusion, cholesterol crystal deposition in basal cell carcinoma was considered to relate to a long disease duration with a tumor in a region that was subject to external irritation. Histopathologically, apoptotic cells around the cholesterol clefts indicated that lipids from the tumor cell membranes were one of the causes of cholesterol crystal deposition.

Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin

Sensitive skin represents hyperactive sensory symptoms showing exaggerated reactions in response to internal stimulants or external irritants. Although sensitive skin is a very common condition affecting an estimated 50% of the population, its pathophysiology remains largely elusive, particularly with regard to its metabolic aspects. The objective of our study was to investigate the pathogenesis of sensitive skin. We recruited healthy participants with 'sensitive' or 'non-sensitive' skin based on standardized questionnaires and 10% lactic acid stinging test, and obtained skin samples for microarray analysis and subsequent experiments. Microarray transcriptome profiling revealed that genes involved in muscle contraction, carbohydrate and lipid metabolism, and ion transport and balance were significantly decreased in sensitive skin. These altered genes could account for the abnormal muscle contraction, decreased ATP amount in sensitive skin. In addition, pain-related transcripts such as TRPV1, ASIC3 and CGRP were significantly up-regulated in sensitive skin, compared with non-sensitive skin. Our findings suggest that sensitive skin is closely associated with the dysfunction of muscle contraction and metabolic homeostasis.

TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor

Detection of external irritants by head nociceptor neurons has deep evolutionary roots. Irritant-induced aversive behavior is a popular pain model in laboratory animals. It is used widely in the formalin model, where formaldehyde is injected into the rodent paw, eliciting quantifiable nocifensive behavior that has a direct, tissue-injury-evoked phase, and a subsequent tonic phase caused by neural maladaptation. The formalin model has elucidated many antipain compounds and pain-modulating signaling pathways. We have adopted this model to trigeminally innervated territories in mice. In addition, we examined the involvement of TRPV4 channels in formalin-evoked trigeminal pain behavior because TRPV4 is abundantly expressed in trigeminal ganglion (TG) sensory neurons, and because we have recently defined TRPV4’s role in response to airborne irritants and in a model for temporomandibular joint pain. We found TRPV4 to be important for trigeminal nocifensive behavior evoked by formalin whisker pad injections. This conclusion is supported by studies with Trpv4−/− mice and TRPV4-specific antagonists. Our results imply TRPV4 in MEK-ERK activation in TG sensory neurons. Furthermore, cellular studies in primary TG neurons and in heterologous TRPV4-expressing cells suggest that TRPV4 can be activated directly by formalin to gate Ca2+. Using TRPA1-blocker and Trpa1−/− mice, we found that both TRP channels co-contribute to the formalin trigeminal pain response. These results imply TRPV4 as an important signaling molecule in irritation-evoked trigeminal pain. TRPV4-antagonistic therapies can therefore be envisioned as novel analgesics, possibly for specific targeting of trigeminal pain disorders, such as migraine, headaches, temporomandibular joint, facial, and dental pain, and irritation of trigeminally innervated surface epithelia.

Atopic dermatitis - all you can do from the outside

Atopic dermatitis (AD) affects both the epidermal barrier and the immune system and, as such, therapy needs to address both. Skin cleansing supported by emollients and moisturizers is the primary topical therapy when treating patients with AD. However, it should be remembered that the direct use of emollients on inflamed skin is poorly tolerated and that the flares need to be treated effectively, usually by topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI). This contribution outlines a number of strategies for effectively managing AD, from reactive therapy using TCS and TCI to proactive therapy. Proactive therapy is an alternative, evidence-based, immunologically founded treatment approach, based on the fact that normal-looking, nonlesional skin of patients with AD is not normal. The advantage of the proactive approach is that the patients are in control of their disease and are actively involved in its management. The avoidance of external irritants is recommended wherever possible.

Co-regulated protein functional modules with varying activities in dynamic PPI networks

Current methods for the detection of differential gene expression focus on finding individual genes that may be responsible for certain diseases or external irritants. However, for common genetic diseases, multiple genes and their interactions should be understood and treated together during the exploration of disease causes and possible drug design. The present study focuses on analyzing the dynamic patterns of co-regulated modules during biological progression and determining those having remarkably varying activities, using the yeast cell cycle as a case study. We first constructed dynamic active protein-protein interaction networks by modeling the activity of proteins and assembling the dynamic co-regulation protein network at each time point. The dynamic active modules were detected using a method based on the Bayesian graphical model and then the modules with the most varied dispersion of clustering coefficients, which could be responsible for the dynamic mechanism of the cell cycle, were identified. Comparison of results from our functional module detection with the state-of-art functional module detection methods and validation of the ranking of activities of functional modules using GO annotations demonstrate the efficacy of our method for narrowing the scope of possible essential responding modules that could provide multiple targets for biologists to further experimentally validate.

Anti-inflammatory activity of garlic oil extract

1. Study of garlic oil acute toxicity. With the administration of drug in dose of 12.5 ml/kg - 25 ml/kg the general behavior of the experimental animals did not differ from controls. The animals were active, took food and water, reacted to external irritation. Whereas the administration of 37.5 ml/kg and 50 mg/kg promoted a marked restriction of movement, breathing became shallow and frequent. Observed changes lasted for 35-45 minutes, then held their own and the state of the animals returned to baseline. In this case, there were no any pathological reactions in animal behavior. They were active, there were no signs of intoxication and they completely ate food. No deaths occurred during the follow-up

Lack of association between passive smoking and asthma prevalence in Mexican children

Lack of association between passive smoking and asthma prevalence in Mexican children

Reply to Liang et al.

This is in response to the letter to the editor by Xin et al. [1] on our original article [2]. According to the article of my colleague Dr Yashiki, in the case of awake OPCAB procedure, it is rather in a parasympathetic tone than sympathetic tone, drops to a lower level. With my own experience of awake surgeries, using high TEA, thorax and upper abdominal area are not affected by external irritation. I found in most patients that BIS monitor shows keeping fully awake but patients are onset of sleep and are able to open their eyes when I call. Patients are not anxious for being kept awake; therefore, fast track does not have negative effect on patients. I would recommend simultaneous use of TEA and GA. This hybrid treatment allows early postoperative awake with less amount of drugs. However, awake surgeries using only TEA are ultimate optimal for patients with severe pulmonary disease who prefer to avoid intratracheal intubation or even extremely severe brain dysfunction with severe cerebral vessel stenosis.

MMSSC Chemotaxis near Porous Surface of Biocompatible NiTi Scaffolds Synthesized by Selective Laser Sintering (SLS)

ABSTRACTMultipotential mesenchymal stromal stem cells (MMSSC) are an excellent model for testing of the toxicity and biocompatibility of natural-tissue-engineering scaffolds (extracellular matrix). Such studies allow prediction of the behavior of implanted materials in the human. In the present work, testing of a three-dimensional prototype of a smart material – nitinol (the intermetallic phase NiTi) – to evaluate chemotaxis and biocompatibility was conducted.Porous samples were synthesized by the selective laser sintering (SLS) method, establishing different surface conditions in the samples. The surface microstructure and roughness were observed by scanning electron microscopy (SEM) and optical microscopy. The results revealed the clear influence of the surface roughness on stem cell proliferation, morphology, and adhesion. The NiTi samples were well tolerated by the cells but the number of focal contacts decreased with increasing porosity. The proliferation speed was 0.694 doubling/day in the control group and 0.532 doubling/day for the NiTi group. Whereas the control group showed immature and actively divided stem cells, cell growth to enormous sizes (i.e., rapid aging) and a fall in fission activity in the proximity of an external irritant (viz., the NiTi scaffold) was observed.

Risk communication as an operation meant to produce and share audiences

In this article, Luhmann's system theory is used as a theoretical framework for analysing the way risk communicators view their social functions. Narrated experiences from risk communicators in practice facilitate an understanding of risk communication as both an external irritation to society and part of the mass communication system. They also aid in clarifying how perceptions of audiences are reflected in the risk-communication strategies. The analysis is based on qualitative data collected from in-depth interviews conducted with 22 risk communicators (scientific professionals, spokespeople and journalists) in Israel. Thematic areas reflected in interviewees' reported strategies embody their perception of audiences. Those themes include: the reduction of complexities; coding and sorting of information; autopoiesis (realisation/non-realisation of the risk); rationality; inherent paradoxes; and schema formation. In sum, the findings suggest that risk communicators play a major role in defining, creating and producing audiences for the mass communication system.

Dentin basic structure and composition—an overview

Dentin is the most voluminous structural component of human tooth. Dentin protects pulp tissue from microbial and other noxious stimuli. It also provides essential support to enamel and enables highly mineralized and thus fragile enamel to withstand occlusal and masticatory forces without fracturing. Furthermore, it is the first vital tissue to meet external irritation, and instead of being merely a passive mechanical barrier, dentin may in many ways participate in dentin–pulp complex defensive reactions. Even though dentin is usually considered as an entity, different parts of dentin may have special qualitative properties that help dentin to meet all of its required demands. The aim of this review is to provide an overview of the basic structure and composition of dentin, including the collagenous components of the dentin organic matrix and minerals. We also describe the specific structural and functional features of the dentin–enamel junction (DEJ), mantle dentin, inter‐ and peritubular dentin, and pulp stones.

The acute surgical management of injury to the helix and antihelix in patients with large body surface area burns

Deformity or loss of the ear may be caused by superficial dermal burns or deep burns. The depth of ear burns is progressive because the ear protrudes from head and is easily affected by external pressure. Therefore, burn wounds of the ear should be debrided as early as possible, before irreversible changes of the cartilage, and covered with healthy tissue. We describe a surgical procedure for treatment of the extensively burned ear. With this technique, the helix is covered by a postauricular advancement flap, and the antihelix is covered by a skin graft. Because the procedure is straightforward and can be completed within a short time, it can be performed at the same time as other life-saving measures. The use of a skin flap permits adequate debridement in terms of both depth and width, minimising the risk of infection. The helix can be reconstructed to provide a natural appearance, and late ulcer formation due to external irritation is prevented. We have treated 15 ears on 11 patients with this procedure and have consistently obtained a satisfactory outcome.

Newborn skincare and the modern nappy

Effective care of newborn skin is based on a thorough understanding of both the physiology and specific environment of infant skin. The essentials of newborn skin care are effective cleansing, effective moisturizing and the maintenance of an effective barrier against external irritants (Kuller et al, 2001). The baby's nappy has been subject to a remarkable number of improvements since the first disposables appeared on the market; from the first use of super absorbent polymers, through to the large scale use of refastenable tape and the incorporation of petrolatum-based ointment transfer systems, to the introduction of the first breathable nappies.

Sanitary napkin contact dermatitis of the vulva: Location‐dependent differences in skin surface conditions may play a role in negative patch test results

I herein report six Japanese female patients with sanitary napkin contact dermatitis of the vulva. This condition may not be uncommon, although only a few reports have been published in Europe and the USA and none from Asia. Routine patch test with a saline-soaked fragment of their sanitary napkins conducted on the flexor surface of the upper arm gave negative results in all the patients, although pruritic dermatitis was clinically reproducible, developing in a delayed fashion, 2-4 days after the use of any brands of sanitary napkin. Moreover, this dermatitis could be avoided by using a tampon together with wearing cotton shorts. These observations suggest that it is a kind of irritant dermatitis that is induced by the wet local conditions as well as by friction caused by wearing a sanitary napkin rather than that due to sanitary napkin components. Resistance of the skin against external irritant stimuli is variable among different body sites and the genital skin, which is covered by thin stratum corneum, is thought to have low resistance against various external irritating and mechanical stimuli induced by wearing a sanitary napkin. Moreover, it is reasonable to presume that the proliferation of the resident microorganisms of the genital skin that takes place under the wet conditions produced by the use of the napkin also plays a role in the induction of such a unique contact dermatitis. Unfortunately, the commonly employed patch testing method performed on the skin of the upper limb or back cannot simulate the local situation occurring on the vulva under the sanitary napkin. We are urgently in need of a modification in patch testing method that is suited to reproduce similar dermatitis in other body locations.

Functional assessment of a washing emulsion for sensitive skin: mild impairment of stratum corneum hydration, pH, barrier function, lipid content, integrity and cohesion in a controlled washing test

Sensitive skin has been described as a skin type with higher reactivity than normal skin and exaggerated reactions to external irritants. Washing with soaps is harmful for barrier-related parameters. Cutaneous irritation induced by cleansing products under exaggerated test conditions, e.g. patch testing, is not necessarily predictive of the irritation occurring under standardized daily use conditions. The purpose of the study was to assess the effect of an improved washing solution for sensitive skin in a half-site comparison on barrier-related parameters. Thirty healthy volunteers with self-reported sensitive and so-called problematic skin performed standardized washings with a soap-free washing emulsion with mild acidity (pH 5.5) for 3 weeks. Test areas were both forearms and the cheek. Non-invasive biophysical measurements of the following skin parameters, epidermal permeability barrier function measured as transepidermal water loss (TEWL), stratum corneum (SC) hydration, pH value, skin surface lipids, skin temperature and SC integrity/cohesion, were assessed prior to the first washing, on days 7, 14 and 21 after beginning the washing procedure. SC cohesion was quantified using two independent methods on D-Squame tapes: optical spectroscopy measuring the absorbance and a protein assay assessing the total protein (Bradford). Both methods showed a good correlation. SC integrity was quantified by measuring TEWL after sequential stripping with D-Squame tapes. The use of the washing emulsion led to a mild damage of the epidermal permeability barrier function with no marked difference to water application. Furthermore, a mild but significant dehydration was assessed after 21 days vs. baseline without any differences between the water-treated and the washing emulsion-treated forearm. On the cheek no dehydration was detectable but the lipid content was reduced under the washing emulsion. The pH value increased in all three test areas after 21 days, again without significant differences between water and the washing solution. SC cohesion was quantified using two independent methods on D-Squame tapes: optical spectroscopy measuring the absorbance and a protein assay assessing the total protein (Bradford). Both methods showed a good correlation. The SC cohesion decreased after 21 days on the water-treated as well as on the washing emulsion-treated arm. The decrease over time was significant when used the optical spectroscopy measuring. A standardized questionnaire revealed positive characteristics of the washing emulsion and good acceptance. The investigated standardized washing model with the endpoints epidermal barrier function, SC hydration, surface pH, skin surface lipids, skin temperature and SC integrity/cohesion showed only mild damage comparable to washing with water.

Expression of osteocalcin and Jun D in the early period during reactionary dentin formation after tooth preparation in rat molars

We examined, in rats, the expression of osteocalcin and Jun D in the early stage of reactionary dentin formation after tooth preparation and the accompanying morphological changes. Reverse transcription/polymerase chain reaction analysis revealed strong expression of osteocalcin mRNA in pulp tissue at 2 and 3 days post-preparation compared with that in control teeth. Light microscopy demonstrated that, at the dentin-pulp interface, damaged odontoblasts were detached from the dentin matrix immediately after preparation, with neutrophils lining the dental surface after 1 day. After 2-3 days, differentiated odontoblasts appeared at the interface. Reactionary dentin with tubular structures was formed under the cavity after 10 days. Immunoelectron microscopy showed that trace amounts of osteocalcin were expressed in odontoblasts at 2 days post-preparation, and abundant osteocalcin was found in the highly developed Golgi apparatus and granules at 3 days post-preparation. Osteocalcin was also found on type I collagen fibrils in newly formed predentin. The existing dentinal tubules were filled with osteocalcin-coated type I collagen fibrils. We observed, by immunohistochemistry, that Jun D was temporally expressed in the nuclei of the odontoblasts at 1 and 2 days post-preparation. However, no Jun D was found in the dental pulp cells at any other time or in control teeth. Thus, osteocalcin expression is correlated with reactionary dentin formation, and Jun D is associated with osteocalcin expression in odontoblasts. Osteocalcin may also serve as an obturator of the dentinal tubules to protect dental pulp vitality against external irritants after preparation.

Porokeratosis Causing Change in Melanocytic Nevi

Porokeratosis is an uncommon cause of clinical change in pigmented lesions. We report two cases of so‐called “collision” lesions, in which the cause of clinical change in melanocytic nevi was porokeratosis. One biopsy was submitted concurrently with a biopsy from another anatomic site, which was a superficial pattern basal cell carcinoma. Both the melanocytic nevus and the basal cell carcinoma contained coronoid lamellae, focal diminution of the granular layer and subjacent dyskeratotic keratinocytes, consistent with disseminated superficial actinic porokeratosis (DSAP). The melanocytic nevus, from the lower back, was a broad compound melanocytic nevus, associated with elongated, pigmented rete (lentiginous) and small melanocytes in the papillary and superficial reticular dermis (superficial congenital pattern). There was no evidence of external irritation. The second case showed a similar coronoid lamella, focal diminution of the granular layer and dyskeratotic keratinocytes. There was additional parakeratosis away from the parakeratotic column and a lichenoid host response, suggesting external irritation.

Essentials of newborn skin care

Effective care of newborn skin is based on a thorough understanding of both the physiology and specific environment of infant skin. The essentials of newborn skin care are effective cleansing, effective moisturizing and the maintenance of an effective barrier against external irritants. An evidence-based clinical practice guideline published by the Association of Women's Health, Obstetric and Neonatal Nurses in the USA confirms that modern baby care products for cleansing, moisturizing and barrier protection, which meet the guidelines for being pH neutral and having a good safety profile, are safe and effective for neonatal skin care.

Pathological dentinogenesis in posteruptiv toot development

The most significant investigations concerning pathological dentinogenesis are reviewed in this article. Previous results point out that odontoblasts behave, either in physiological or pathological circumstances, in the genetically determined sequence of reactions dependind on the intensity of the irritation. Biochemical research has not yet succeed in getting to the heart of interaction processes. The therapy should be aimed at establishing biological interactions nessesary for normal dentinogenesis mainly by removing external irritations as fast as possible.