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One of the well-known enzymatic debriders is a papain–urea-chlorophyllin ointment. The purpose of this study was to determine the efficacy of this ointment compared with single variable Papain-urea, Copper chlorophyllin, or Urea base ointment and moist wound care in porcine full thickness wounds. Twenty full thickness wounds were made on the dorsum of domestic pigs. Following hemostasis, the wounds were contaminated with wound-isolated bacteria, treated with test articles, and dressed with moisture-retentive dressing. All the wounds were evaluated 1, 4, 8, 11, 14, 18, and 21 days postsurgery visually and biopsies were obtained for microscopy. The results showed no impairment in the rate of epithelialization of the papain–urea-chlorophyllin treatment, nor with single variable actives compared with moist wound care. Microscopic examination revealed an increase in the number of keratinocytes present in the epidermis of the papain–urea-chlorophyllin and papain-treated wounds, and an increase in the depth of rete pegs. Blood vessel formation was increased in the papain–urea-chlorophyllin, papain, and Copper chlorophyllin groups compared to the moist control tissue as seen with CD31 and von Willebrand Factor staining, and was most evident in the papain–urea-chlorophyllin-treated tissues. VEGF was increased after 1 week in the wounds treated with papain–urea-chlorophyllin and papain compared to vehicle, indicating a possible mechanism for neovascularization. The increase was not seen in the Copper chlorophyllin group, indicating the possibility of another mechanism for blood vessel formation in this group. The healing appears to be most complete in the papain–urea-chlorophyllin group based on epidermal morphology and enhanced vascularization, which is vital in supplying nutrients to the newly healed wound.

Oral verruciform xanthoma (OVX) is an uncommon lesion that appears on the oral mucosa. The aim of this paper was to discuss the probable etiopathogenesis of OVX in the hard palate, reinforcing the importance of including this lesion in the differential diagnosis of verrucous lesions. A 43-year-old male smoker presented with a painless lesion with a verrucous surface and erythematous spots on the hard palate. Excisional biopsy revealed oral mucosa consisting of hyperkeratosis, acanthosis, and elongated rete pegs. Subjacent connective tissue showed numerous foam cells with clear cytoplasm and pyknotic nucleus, negative on periodic acid-Schiff staining. Immunohistochemical analysis revealed foam cells positive for anti-CD68 antibody, while anti-KI-67 antibody was restricted to the basal layer of the oral epithelium. A final diagnosis of OVX was established. The patient showed no signs of recurrence after seven months of follow-up. Physical trauma and smoking habits can be directly related to the etiology of verruciform xanthoma because the lesion is chronic and inflammatory with slow growth, and sites if high trauma are more often affected by such a lesion. The hard palate is the second most commonly affected site, and local trauma caused by smoking can be a cause of this type of lesion.

Keratocystic odontogenic tumor commonly occurs in the posterior body and ramus of the mandible. Rarely, however, it develops in the attached gingiva or alveolar mucosa and exhibits the same histopathologic features. The lesion clinically resembles a gingival cyst in adults. Differential diagnosis is therefore difficult. We encountered a case of keratocystic odontogenic tumor arising in the mandibular gingiva and report it as a peripheral keratocystic odontogenic tumor.A 53-year-old man was referred to our department because of an asymptomatic swelling measuring 6 mm in diameter at the gingiva attached to the labia near teeth 2 3. The swelling was covered with normally appearing mucosa and had a whitish hue. The lesion was fluctuant on palpation and had neither spontaneous pain nor tenderness. The teeth adjacent to the lesion were noncarious, and confirmed pulp vitality by electrical stimulation. The lesion was totally excised with a 1-mm margin of normal gingiva under local anesthesia. The alveolar bone adjacent to the lesion had undergone pressure resorption. Exposure of the root surface of 2 3 was noted intraoperatively. Histopathologically, a cystic space was located within the gingival soft tissue. It was lined by parakeratotic stratified squamous epithelium composed of several cell layers and lacking rete pegs. No recurrence was noted for 6 years.

Myeloid sarcoma is an extramedullary malignancy of myeloblasts. An unusual case of myeloid sarcoma presenting in the gingiva and affected by drug-induced gingival enlargement is presented.A 63-year-old male taking amlodipine for his hypertension presented with a 3-week gingival enlargement. Although the obvious clinical impression was that of drug-induced gingival enlargement, an incisional biopsy was performed to corroborate chemical enlargement while ruling out diseases such as lymphoma and leukemia.Microscopic examination of the thickened gingiva revealed surface stratified squamous epithelium having needle-like rete pegs characteristic of drug-induced gingival enlargement. Beneath the surface epithelium, the fibrous tissue was virtually replaced by a dense infiltrate of malignant cells. Immunohistochemical studies were performed with CD117 and myeloperoxidase identifying the malignant cell population as myeloblasts, leading to a diagnosis of myeloid sarcoma.Myeloid sarcoma and hematopoietic malignancies must be included in a differential diagnosis of gingival enlargement until the definitive diagnosis is reached by histologic/laboratory examination.

Objective: To elucidate the immunohistochemical characteristics of oral verruciform xanthomas and the aetiology of foam cells. Patients and Methods: Oral verruciform xanthomas surgically extirpated from 5 patients were examined using immunohistochemistry. Results: The verruciform xanthomas revealed an accumulation of foam cells with clear cytoplasm in the connective tissue around the elongated epithelial rete pegs. The foam cells were intensely positive for CD-68, lysozyme, and vimentin, and were weakly positive for α-1-antitrypsin, but were negative for total keratin and S-100 protein. A small number of dendritic cells were found among the foam cells and were positive for S-100 protein. Conclusions: The findings suggest that the foam cells in oral verruciform xanthomas are of monocytemacrophage lineage and are associated with a local inflammatory immune mechanism similar to verruciform xanthomas of other organs.

Five camelid mucocutaneous fibropapillomas with histologic features similar to equine sarcoids were diagnosed. They were characterized by a dermal fibroblastic proliferation and overlying, often ulcerated hyperplastic epidermis with thin rete pegs extending down into the dermis. Two of the tumors came from llamas and three from alpacas. Four of the animals were 6-year-old females. The fifth was a 6-year-old castrated male. The fibropapillomas were located on the nose, lip, and cheeks. One of the llama tumors waxed and waned before surgery and recurred and spread after surgery. None of the other tumors recurred. All five tumors were positive for papillomavirus (PV) DNA by polymerase chain reaction testing. Nucleotide sequence analysis of the PCR product from one of the llama fibropapillomas confirmed a unique PV. This report provides the microscopic and clinical features of fibropapillomas in camelids as well as evidence for a PV etiology.

© 2015, Nizhny Novgorod State Medical Academy. All rights reserved. Optical coherence tomography (OCT) generates its primary form of contrast from elastic backscatter. It is now the gold standard technique for retinal screening and is emerging rapidly in cardiovascular research however it remains a research goal to establish it to the same degree in epithelial cancer detection and diagnosis. In this report we compare two different OCT systems: an 890 nm spectrometer-based OCT system with 2.5 µm axial resolution and a 1300 nm swept-source OCT system with 7.5 µm axial resolution to determine the effect of these different OCT parameters on the endogenous backscatter contrast of dysplastic/malignant oral mucosa models relative to normal mucosa models. Tissueengineered oral mucosa models constructed with a dysplastic cell line (DOK), a malignant cell line (Cal27) and normal cell were imaged with both of these OCT platforms and comparisons made with regard to apparent epithelial thickness and the visibility of the epithelium relative to the underlying stroma. For the Cal27’s, hematoxylin and eosin staining confirmed the formation of a keratinized layer superficial to a thickened layer of viable cells on top of the stroma. The keratinized layer presented as a hyperreflective thickened layer superficial to a darker region on both OCT platforms. The keratinized layer caused a steep fall in signal at 890 nm, making it difficult to visualise underlying structures, whereas 1300 nm OCT clearly visualized both the epithelial cells and the stroma lying beneath. For the DOK cells, hematoxylin and eosin staining confirmed the formation of an epithelial layer frequently presenting an abnormal morphology especially at the epidermal/stromal junction, with features such as infiltrating, bulbous rete pegs. These were more clearly visualized under 890 nm OCT. These observations show that 890 nm OCT retains some of its known advantages of higher contrast between anatomical tissue layers when used to observe dysplastic and malignant 3D oral mucosa constructs. However 1300 nm OCT is confirmed to possess a greater ability to image the full thickness of the model epithelia and in particular it is more suited to imaging through the keratinized layer.

Objectives.The habit of khat chewing is prevalent in many Middle Eastern and African cultures and has been associated with various adverse conditions in humans. This study aimed to describe histological changes induced by chronic khat chewing on the buccal mucosa.Methods.Biopsies of the buccal mucosa from 14 chronic khat chewers, 20 chronic khat chewers who also smoked tobacco, and 8 nonchewers were compared for epithelial thickness, degree and type of keratinization, and connective tissue changes.Results.Tissues from khat chewers depicted abnormal keratinization of the superficial cell layer and showed increased epithelial thickness affecting all layers. Epithelial thickness in control samples was 205 ± 26 μm whereas thickness in khat chewers and khat chewers who smoked tobacco was significantly higher measuring 330 ± 35 μm and 335 ± 19 μm, respectively. Tissues from khat chewers also showed increased intracellular edema, increased melanin pigment deposits, and increased number of rete pegs most of which were thin and deep.Conclusions.These results show that oral lesions induced by chronic chewing of khat in the buccal mucosa present with white and brown discoloration due to increased epithelial thickness, increased keratinization, and melanin deposition.

Oral squamous cell papilloma (OSCP) is a benign proliferation of the stratified squamous epithelium, which results in a papillary or verrucous exophytic mass. OSCP is usually associated with human papilloma virus. Although any surface of the oral cavity can be affected, the sites of predilection for localization of the lesions include the tongue, lip and soft palate. In this report, treatment and histological findings of a local gingival enlargement at the vestibular side of the upper right central tooth of a 10 year-old systemically healthy girl are presented. The lesion was asymptomatic and had shown a slow growth. Solitary, exophytic lesion was clinically soft, pink-white in color and appeared as cauliflower. Dental and periodontal tissues were radiographically normal. One month after scaling and root planing, under local anesthesia the lesion was excised and this was followed by the use of Nd: YAG laser (1064 nm, 20 Hz, 3 W) to control bleeding, minimize pain and scarring in post-operative period, and provide sterilization. Macroscopic examination revealed that the lesion was 1.1×0.5×0.2 cm3 in size, yellow in colour and had a rough surface, while histological examination showed multi-layer connective tissue underlying the squamous epithelium, numerous rete pegs and spinous cell proliferation at the papillary and OSCP was diagnosed. There was no evidence of viral cytopathic effect or malignancy of the lesion. No recurrence was observed during the 4-year follow-up period., Oral skuamöz hücreli papillom (OSHP), çok katlı epitelin benign proliferasyonu sonucu meydana gelen papiller veya verrüköz ekzofitik kitledir ve genellikle human papilloma virüs ile ilişkilendirilir. Ağzın herhangi bir yerinde görülebilen lezyonların yerleşim alanı sıklıkla dil, dudak ve yumuşak damaktır. Sistemik olarak sağlıklı 10 yaşındaki kız çocuğunun üst sağ santral dişinin vestibül yüzeyinde soliter saplı, yumuşak, pembe-beyaz renkli ve karnabahar görünümündeki lezyonun asemptomatik olduğu ve 1 yıldır yavaş büyüme gösterdiği öğrenildi. Bölgenin periapikal radyografisinde dental ve periodontal dokuların normal olduğu gözlendi. Diş yüzeyi temizliği ve kök yüzeyi düzleştirilmesinden 1 ay sonra lokal anestezi altında lezyon bistüriyle eksize edildi; takiben kanama kontrolünün sağlanması, post-operatif dönemde minimal ağrı ve skar oluşumu, ve dezenfeksiyon sağlanması amaçlarıyla Nd:YAG lazer (1064 nm, 20 Hz, 3 W) uygulandı. Makroskopik olarak 1.1×0.5×0.2 cm3 boyutlarında, sarı renkli ve yüzeyi pürtüklü lezyonun histolopatolojik incelemesinde, çok katlı epitel altında bağ dokusu, çok sayıda rete pegler ve papiller kısımda spinöz hücre proliferasyonu izlendi ve OSHP tanısı kondu. Lezyonda viral sitopatik etki veya malignite bulgusuna rastlanmadı. Hastanın 4 yıllık takibinde rekürrans görülmedi.

Recent experiments have shown that in patients with psoriasis, highly elevated levels of nitric oxide (NO) are released at the surface of psoriatic plaques. Nitric oxide is a central biological regulator of many aspects of physiology, and it is a natural possibility that the high nitric oxide levels in psoriasis play a causal role in the onset of the disease. Here, we use mathematical modelling to investigate this possibility. We begin by discussing a simple model consisting of a single equation for nitric oxide concentration, which enables nitric oxide secretion rates in the basal epidermis to be calculated from the observed NO release rates at the skin surface. Using this key parameter value, we then develop an extended model that tests the hypothesis that nitric oxide regulates the formation of the extended rete pegs seen in psoriatic plaques. This occurs via the peroxynitrite-dependent activation of the collagenase MMP-8, which is produced by neutrophils present at high levels in psoriatic plaques. The plausibility of the hypothesis is demonstrated and specific testable quantitative predictions about the roles of the various cell types and signalling molecules are made.

OBJECTIVE: To analyze the onset and extent of the dermatological changes associated with microdermabrasion. METHODS: Eleven volunteers, aged 31-62 years old, underwent a series of six aluminum oxide microdermabrasion facial treatments spaced over 7 to 10-day intervals. White light photography and digital ultraviolet fluorescent photography and skin biopsies were obtained prior to the study, after three treatments, and after six treatments. A 90-day no-treatment period ensured, after which biopsies and photographs were taken. RESULTS: Clinical improvements in dyschromia, actinic changes and fine rhytides were observed after six treatments. Compared with the controls, the treated areas demonstrated the following histological changes: epidermal thickening with basal cell hyperplasia and mitotic activity; flattening and widening of the rete pegs; papillary dermal thickening with deposition of collagen and elastic fibers; and perivascular inflammation in the dermis. After the no-treatment period some of the clinical and histologic changes persisted although they were less than those present immediately after the last treatment. Serial ultraviolet photography following microdermabrasion treatments revealed changes in the skin's pigmentation pattern that correlated clinically with improvements in dyschromia. CONCLUSION: Clinical and histological changes are most likely secondary to a mechanism resembling a reparative process. The persistent changes after a period of no-treatment suggests that some of the changes could be permanent. Clinicians can use this data to better determine the optimal interval frequency and treatment intervals with microdermabrasion.

To investigate the relationship between histological changes and distributions of medullasin, a neutrophil elastase-like serine proteinase, in phenytoin-induced gingival overgrowth, we established a rat model of gingival overgrowth. Thirty-two, 20-day-old male Fischer 344 rats were fed a diet containing phenytoin and sacrificed at 1, 2, 4 and 8 weeks. Control rats (n = 40) were fed the same diet, but without the drug and killed at the same weeks as experimental rats (n = 32) and 0 week (n = 8). The mandible specimens were resected and sectioned bucco-lingually between the first and second molars. A marked inflammatory-cell infiltration and elongated rete pegs were seen in the phenytoin-treated group. The extent of the overgrowth assessed by computer image analysis and the density of medullasin-positive cells by immunohistochemistry in the approximal gingiva showed a significant increase in the phenytoin-treated group compared to the control group. A marked infiltration of the positive cells in experimental rats was observed as early as 2 weeks when gingival overgrowth was not fully established. Medullasin-positive cells were mostly neutrophils and partly macrophage-like cells. These findings suggest that medullasin may be involved in mainly host defense and secondarily collagen metabolism in the phenytoin-induced rat model of gingival overgrowth.

Clinical, anatomical and histological aspects of the equine acoustic organ have been poorly investigated and illustrated in literature so far. It is understood that an intact acoustic organ and hearing function are of vital importance for the well-being of flight animals like horses. The knowledge of the acoustic organ is usually transferred analogously from other mammals to horses. The purpose of this study was to provide a detailed and complete histological description of the healthy equine auditory organ, and to determine its congruity to other mammalians. Anatomical dissections and histological preparations were carried out on ten cadaver heads. Specimens of various parts of the equine acoustic organ were taken and evaluated histologically. The histological composition of external, middle and inner ear structures are predominantly congruent to those of other mammals, especially to human beings. Unique inwardly directed rete pegs within the osseous ear canal and the prominent tensor tympani muscle are described for the first time. Results obtained in this study can be employed as references for further research on the equine acoustic organ and improve the understanding of the clinical development of hearing loss, otitis externa/media/interna or tympanosclerosis.

The innervation of the digits on the raccoon forepaw was examined by using immunochemistry for protein gene product 9.5, calcitonin-gene related peptide, substance P, neuropeptide-Y, tyrosine hydroxylase, and neurofilament protein. The larger-caliber axons in the ventral glabrous skin terminate as Pacinian corpuscles deep in the dermis, small corpuscles and Merkel endings around the base of dermal papillae, and Merkel endings on rete pegs in dermal papillae. Extensive fine-caliber innervation terminates in the epidermis and on the microvasculature. The innervation is more dense in the distal than in the proximal volar pads. Pacinian endings are also concentrated in the transverse crease separating the distal and proximal pads. In the dorsal hairy skin, hair follicles are well innervated with piloneural complexes. Merkel innervation is located under slight epidermal elevations and in some large Merkel rete pegs located at the apex of transverse skin folds just proximal to the claw. No cutaneous Ruffini corpuscles were found anywhere on the digit. The claw is affiliated with dense medial and lateral beds of Pacinian endings, bouquets of highly branched Ruffinilike endings at the transition from the distal phalanx and unmyelinated innervation in the skin around the perimeter. Encapsulated endings are located at the lateral edge of the articular surface of the distal phalanx. Extensive fine-caliber innervation is affiliated with sweat glands and with the vasculature and is especially dense at presumptive arteriovenous sphincters. Virtually all of the sweat gland and vascular innervation is peptidergic, whereas most of the unmyelinated epidermal innervation is nonpeptidergic. J. Comp. Neurol. 417: 467‐ 490, 2000. © 2000 Wiley-Liss, Inc. Indexing terms: digit; cutaneous innervation; vascular innervation; sensory endings

Malassez epithelium has been designated as epithelial cell rests, the biological significance of which is still under debate. This study was designed to analyze Malassez epithelium for the presence of neuroendocrine cells. Gingival tissue was included as a positive control. Using immunohistochemistry, confocal and light microscopy, Malassez epithelium and gingival epithelium from mature cats (n = 5) were examined for cells containing the neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP). Both Malassez epithelium and the basal epithelial cell layers in gingival rete pegs regularly displayed cells immunoreactive to CGRP, SP, and VIP. The immunopositive cells were most frequently present in the epithelial cell clusters and strands of Malassez located in the cervical half of thc periodontal ligament. Double immunolabeling revealed cellular co-expression of CGRP or SP with VIP, and the neuropeptides were co-localized in the cellular compartments. Labeled cells in both epithelia were occasionally supported by immunoreactive nerve fibers. This study shows that cells immunoreactive to CGRP, SP, and VIP arc located within the cat Malassez epithelium. The localization of neuroendocrine cells verifies the diversity of this epithelium and confirms that Malassez epithelium is composed of different cell types, in common with epithelia from other locations. The presence of neuroendocrine cells in Malassez epithelium strongly suggests biological functions of this tissue, and the neuropeptide content may thus indicate endocrine functions of the cells.

Mice that lack the extracellular matrix protein thrombospondin 2 have, among several abnormalities, an increase in vascular density, abnormal collagen fibrils, and dermal fibroblasts that are defective in adhesion. These findings suggested that responses involving these processes, such as wound healing, might be altered. To investigate the healing process, excisional wounds were made with the aid of a biopsy punch. Such wounds, observed over a 14 d period, appeared to heal at an accelerated rate and with less scarring in thrombospondin 2-null mice. Histologic analysis of thrombospondin 2-null wound sites revealed the presence of an irregularly organized and highly vascularized granulation tissue. In addition, thrombospondin 2-null wounds retained a higher total cellular content, than control wounds. No differences in wound re-epithelization rates were observed, but thrombospondin 2-null epithelia formed rete pegs and were thicker than control epithelia. By immunohistochemistry, we detected elevated levels and an irregular deposition pattern for fibronectin in thrombospondin 2-null wounds, observations that correlated with the abnormal collagen organization in the granulation tissue. Immunostaining for thrombospondin 2 in control wounds showed that the protein is present in both early and late wounds, in a scattered cell-associated pattern or widely distributed cell- and matrix-associated pattern, respectively. Our results suggest that thrombospondin 2 plays a crucial part in the organization and vascularization of the granulation tissue during healing, possibly by modulating fibroblast-matrix interactions in early wounds and regulating the extent of angiogenesis in late wounds.

This study was performed to clarify the in vivo damage to periodontal tissue induced by lipopolysaccharide (LPS) from Actinobacillus actinomycetemcomitans Y 4 and Porphyromonas gingivalis 381, which penetrate the junctional epithelium. Each LPS solution (5 mg/ml) was continuously dropped into the gingival sulcus of the lower first molar of a Lewis rat for 30min every 24h. The animals were sacrificed 30min after the 1st, 3 rd, 7th, 10th and 15th administration and their mandibles were examined histopathologically and histomorphometrically (n=25 in each group). A gradual increase in inflammatory findings was observed in both LPS groups. However, A. actinomycetemcomitans LPS induced more marked inflammation and degeneration of periodontal tissue. Loss of connective tissue attachment and rete peg elongation were significantly greater in rats administered with A. actinomycetemcomitans LPS compared to those administered with P. gingivalis LPS. Degeneration of junctional epithelium and subepithelial connective tissue was found at the 1st and 3rd administrations. At the 7th and 10th administrations, epithelial cells and collagen fibers were detached from root surfaces. Rete pegs showed deep invasion toward alveolar bone and epithelial detachment downward migration. At the 15 th administration, osteoclastic bone resorption was in some cases observed on the alveolar bone crest in the A. actinomycetemcomitans LPS group. These findings suggest that A. actinomycetemcomitans LPS had a greater effect on periodontal tissue destruction than P. gingivalis LPS.

Eyelid skin characteristically has no rete pegs; lanugo hairs without erector pili are present, and there is no subcutaneous fat or stratification of dermis into defined zones. The eyelid epidermis consists of four layers: the stratum corneum, stratum granulosum, stratum spinosum, and stratum germinativum. The stratum germinativum also is known as the basal layer. The dermis is composed of important structures such as hair, glands, nerves, and vessels.

A 4-year-old child was referred, in April 1988, to Rennes Dental School (France) for deciduous tooth mobility with premature loss of 4 deciduous teeth and germs of 2 permanent incisors. Microbiological examinations by culture revealed the presence of the periodontal pathogen Actinobacillus actinomycetemcomitans. Immunofluorescence of plaque samples revealed the presence of Porphyromonas gingivalis that had not been isolated by culture. Neutrophil functions were within normal ranges. Transmission electron microscopy of gingiva showed a disorganised epithelium. The connective tissue was infiltrated by inflammatory cells. The basement membranes were normal, but the connective tissue-epithelium interface was mainly composed of short rete pegs. Scanning electron microscopy of extracted deciduous teeth revealed lack of cementum, lacunae in the cementum and lack of fibrillar insertion on the middle part of the root. Skin lesions, mainly situated on face, were observed. Treatment was by extraction of mobile deciduous teeth combined with 3-week courses of metronidazole. Clinical and microbiological follow-up was continued over a 7-year period. No periodontal lesions have been detected since eruption of the permanent teeth. The present subgingival and lingual microflora (December 1995) is composed of bacteria associated with periodontal health. However, the future appearance of a hitherto undetected systemic disease is still possible.

The daily topical application of two compounds, a cream containing 10% evening primrose oil (EPO) and Lioxasol (a compound used clinically to treat radiation burns), resulted in increased cell proliferative activity in the skin of female Large White pigs. The effect was most pronounced in the case of the EPO based cream, and was comparable in magnitude with that observed in a previous study on pig skin using orally administered EPO. There was an increase in the size of the rete pegs in the epidermis by 6 weeks after the start of application of the EPO cream. However, this did not translate into an increase in the total thickness of the viable epidermis (excluding the stratum corneum) due to a reduction in the density of rete pegs, from 2 weeks after treatment. Lioxasol had no overall effect on the size of the rete pegs. The labelling index (LI) of cells in the basal layer of the epidermis of pigs receiving a daily topical application of EPO increased progressively with time from the start of application. The LI was maximal (17.9 +/- 2.4%) at the end of the observation period (8 weeks) at which time it was a factor of approximately 2 higher than in the basal layer prior to treatment. A considerably less marked increase in the LI of the basal layer was seen after the application of Lioxasol. The overall increase was approximately 20%, relative to the LI in the untreated epidermis. Labelled cell nuclei were also counted in the papillary dermis. After the application of the EPO cream, no significant increase in the number of labelled cells was observed until week 8, at which time values were approximately twice those in untreated skin. In Lioxasol treated skin the effect on the numbers of labelled cells in the papillary dermis was more immediate, with a approximately 60% increase at 2 weeks. This enhanced level of labelling was maintained until the end of the observation period of 10 weeks. Studies on the cell kinetics of the skin using the alcohol component of the Lioxasol preparation suggested that alcohol rather than Lioxasol was the most significant ingredient. It was concluded that the EPO cream merited further evaluation as a potential modulator of skin response to ionizing radiation.

The use of cyclosporine A (CsA) induces hyperplasia of the gingival epithelium in a site-specific response manner, but the molecular mechanism via which the lesion occurs is unclear. The present research aims to investigate the site-specific effect of CsA on the apoptosis of gingival epithelium associated with gingival hyperplasia.Forty Wistar rats were divided into CsA-treated and non-treated groups. Paraffin-embedded sections of mandibular first molars were selected for hematoxylin and eosin staining, immunohistochemistry analyses of bcl-2 and caspase-3, and the staining of terminal deoxynucleotidyl transfer-mediated dUTP nick-end labeling (TUNEL). The area of the whole gingival epithelium and the length of rete pegs were measured, and the number of bcl-2- and caspase-3-positive cells in the longest rete peg were counted. The analysis of variance for factorial designs and Fisher least significant difference test for post hoc analysis were used to determine the significance levels.In CsA-treated rats, bcl-2 expression was significantly upregulated, whereas caspase-3 expression was downregulated, along with a reduced number of TUNEL-positive cells. The site-specific distribution of bcl-2 was consistent with the site-specific hyperplasia of the gingival epithelium in CsA-treated rats.CsA inhibited gingival epithelial apoptosis via the mitochondrial pathway and common pathway. The antiapoptotic protein bcl-2 might play a critical role in the pathogenesis of the site-specific hyperplasia of gingival epithelium induced by CsA. There were mechanistic differences in the regulation of apoptosis for cells in the attached gingival epithelium, free gingival epithelium, and junctional epithelium.

Intrinsic (chronological) skin ageing is characterized by atrophy of the skin with loss of elasticity and slowed metabolic activity. The superposition of environmental damage, particularly exposure to ultraviolet radiation (photodamage), on the intrinsic ageing process results, at least initially, in a hypertrophic repair response, with a thickened epidermis and increased melanogenesis. Even more striking changes occur in the dermis: massive elastosis (deposition of abnormal elastic fibres), collagen degeneration, and twisted, dilated microvasculature. Regular use of a sunscreen alone appears to allow some repair as well as protection from further photodamage. Topical tretinoin has been shown to partially reverse the clinical and histological changes induced by the combination of sunlight exposure and chronological ageing. A formulation of tretinoin in an emollient cream (Retinova, Renova), developed specifically for the treatment of photodamaged skin, has been extensively investigated in multicentre, double-blind trials and has been shown to produce significant improvement within 4-6 months of daily use, compared with vehicle alone, as part of a regimen including sun protection and moisturizer use. Histological changes in the epidermis and dermis noted after 12 months suggest tretinoin repairs photodamage by reconstitution of the rete pegs, repair of keratinocyte ultrastructural damage, more even distribution of melanocytes and melanin pigment, deposition of new papillary dermal collagen, and improvements in vasculature. Alpha-hydroxy acids (AHAs) have also been widely used for therapy of photodamaged skin, and these compounds have been reported to normalize hyperkeratinization and increase viable epidermal thickness and dermal glycosaminoglycans content. The single randomized controlled study now available appears to substantiate AHA efficacy and safety. In summary, recent work has substantially elucidated the ageing processes that affect the skin and has demonstrated that many of the unwanted changes can be improved by topical therapy.

Establishing direct and causal relationships among the confederacy of activated cell types present in psoriasis has been hampered by lack of an animal model. Within psoriatic plaques there are hyperplastic keratinocytes, infiltrating immunocytes, and activated endothelial cells. The purpose of this study was to determine if psoriasis is primarily a disorder of keratinocytes or the immune system. Using a newly developed experimental system in which full-thickness human skin is orthotopically transferred onto severe combined immunodeficient mice, autologous immunocytes were injected into dermis, and the resultant phenotype characterized by clinical, histologic, and immunophenotypic analyses. Engraftment of samples included both uninvolved/ symptomless (PN) skin removed from patients with psoriasis elsewhere, or from healthy individuals with no skin disease (NN skin). In 10 different experiments involving 6 different psoriasis patients, every PN skin was converted to a full-fledged psoriatic plaque skin by injection of autologous blood-derived immunocytes. In all but one psoriatic patient, the immunocytes required preactivation with IL-2 and superantigens to convert PN skin into psoriatic plaque skin. In every case, resultant plaques were characterized by visible presence of flaking and thickened skin, loss of the granular cell layer, prominent elongation of rete pegs with a dermal angiogenic tissue reaction, and infiltration within the epidermis by T cells. Lesional skin displayed 20 different antigenic determinants of the psoriatic phenotype. None of the four NN skin samples injected with autologous immunocytes converted to psoriatic plaques. We conclude that psoriasis is caused primarily by the ability of pathogenetic blood-derived immunocytes to induce secondary activation and disordered growth of endogenous cutaneous cells including keratinocytes and vascular endothelium.

Background The dorsal extension of the tip of the trunk of Asian elephants (Elephas maximus), often referred to as “the finger,” possesses remarkable mechanical dexterity and is used for a variety of special behaviors including grasping food and tactile and ultimately chemosensory recognition via the vomeronasal organ. The present study describes a unique sensory innervation of this specialized region of the trunk. Methods The tip of the dorsal aspect of the trunk is referred to as the trunk tip finger and has been studied grossly in 13 living elephants. One tip from a male Asian elephant was obtained for histologic study when it was accidentally severed. The tissue was fixed in 10% neutral buffered formalin, and portions were either sectioned frozen or embedded in paraffin and serial sectioned. Sections were stained with silver in both cases. Results The skin of the trunk tip finger differs from that of the surrounding areas; it contains a high density of free nerve endings, numerous convoluted branched small corpuscles, and vellus vibrissae that resemble vellus hairs, which do not protrude beyond the skin surface. The finger is thus densely innervated with three distinctive types of sensory terminals. Corpuscular receptors consist of small Pacinian corpuscles and convoluted branched simple corpuscles. Both are present in the superficial dermis. Abundant regular vibrissae are present in the skin surrounding the trunk tip finger. Short vibrissae that do not protrude from the skin surface, referred to as vellus vibrissae, are abundant in the finger tip. Both types of vibrissae are innervated by hundreds of axons resembling the mystacial vibrissae of rodents. Free nerve endings are numerous in the superficial dermis, often making intimate contact with the basal cells of rete pegs. Conclusions The dorsal finger of the trunk tip of Asian elephants has a unique sensory innervation that resembles aspects of sensory innervation of mystacial skin of rodents or lip tissue of monkeys. This dense sensory innervation can be correlated with the tactile ability of these animals to use the trunk finger to grasp small objects for feeding and to insert chemically active samples into the ductal orifices of the vomeronasal organ for subsequent chemosensory processing. © 1996 Wiley-Liss, Inc.

Background Monosodium glutamate (MSG) is an accepted commonly used flavor enhancer and food additive. However, incautious abuse of this food additive may occur because of its abundance, mostly without labeling, in many food ingredients. Objective The objective of this study was to investigate the genotoxic potential of MSG on rat palatal mucosa. Materials and methods Forty-two mature albino rats weighing 200–250 g at the age of 6 weeks were used in this study. They were allocated to evenly three groups, each group of 14 animals. Group I was maintained as control group. Rats in group II and group III were administered MSG at two different doses, 20 and 40 mg/kg body weight respectively for 2 months. Palatal mucosa samples were dissected then divided into two halves. The first half was fixed in formal saline solution then processed to be stained with hematoxylin and eosin stain. The second half was frozen to be prepared for the molecular study. Results General histological examination presented acanthosis and hyperkeratosis in group II while group III revealed papillary fold projections and bulbous shaped rete pegs together with atypical cellular changes in the basal cell layer of the oral epithelium. Molecular results proved marked reduction in DNA quality and quantity in both experimental groups in comparison to control group. The reduction in DNA quantity was more pronounced in group III using four different primers. Conclusion It was concluded that MSG has genotoxic effects on the palatal mucosa of rats that was clearly detected in routine histological findings and DNA molecular results.

We examined the morphology of chin and lip facial projections of seven species of Phyllostomid and Noctilionid bats utilizing scanning electron microscopy and light microscopy of immunohistochemical and stained paraffin-embedded sections. Results showed that lip and chin facial projections were composed of glabrous skin except for some chin projections of Noctilio leporinus that were composed of haired skin. All projections contained a rich and diffuse concentration of nerves that were associated with dermal papillae and epidermal rete pegs that contained Merkel cell–neurite units and a diffuse network of epidermal free nerve endings. The existence of physically extended anatomical structures that contain a variety of receptor sensory units and their associated modalities must be important to be present throughout this diverse group of bats. These facial projections include a unique neural arrangement, but their specific functions remain unknown.

Rapid coverage and epithelial closure of extensive burns remains a major requirement for patient recovery. Although many skin substitutes have been described, permanent regeneration of both epithelial and connective tissues after a single surgical application of a skin substitute has not become routine. To replace both dermal and epidermal skin, cultured skin substitutes (CSS) were prepared from autologous keratinocytes and fibroblasts seeded onto collagen-glycosaminoglycan (C-GAG) substrates. CSS were applied to excised, full-thickness burns on 5 patients. Histologic analysis showed a fully stratified, hyperkeratotic epidermis within 12 days of grafting with little to no evidence of an inflammatory reaction. Epidermal and connective tissues are interdigitated in analogy to rete pegs and dermal papillae, and the neovascular plexus approximates the dermal-epidermal junction. Transmission electron microscopy identified a continuous basement membrane with hemidesmosomes and anchoring fibrils that connected the epidermis with the underlying connective tissue. Within 14-28 days, the C-GAG had been degraded and replaced by newly synthesized collagen in regenerated connective tissue. Spontaneous repigmentation of healing CSS from passenger melanocytes in keratinocytes culture was observed within 2 months after grafting. Electron microscopy revealed the presence of numerous melanosomes within the keratinocytes, illustrating pigment transfer between melanocytes and keratinocytes after wound closure. These results demonstrate that the CSS develop into functional permanent skin tissue capable of spontaneous repigmentation after grafting onto burn wounds.

Background: Optical coherence tomography (OCT) is a non-invasive optical technology using near-infrared light to produce cross-sectional tissue images with lateral resolution. Objectives: The overall aims of this study was to generate a bank of normative and pathological OCT data of the oral tissues to allow identification of cellular structures of normal and pathological processes with the aim to create a diagnostic algorithm which can be used in the early detection of oral disorders. Material and methods: Seventy-three patients with 78 suspicious oral lesions were referred for further management to the UCLH Head and Neck Centre, London. The entire cohort had their lesions surgically biopsied (incisional or excisional). The immediate ex vivo phase involved scanning the specimens using optical coherence tomography. The specimens were then processed by a histopathologist. Five tissue structures were evaluated as part of this study, including: keratin cell layer, epithelial layer, basement membrane, lamina propria and other microanatomical structures. Two independent assessors (clinician and pathologist trained to use OCT) assessed the OCT images and were asked to comment on the cellular structures and changes involving the five tissue structures in non-blind fashion. Results: Correct identification of the keratin cell layer and its structural changes was achieved in 87% of the cohort; for the epithelial layer it reached 93.5%, and 94% for the basement membrane. Microanatomical structures identification was 64% for blood vessels, 58% for salivary gland ducts and 89% for rete pegs. The agreement was “good” between the clinician and the pathologist. OCT was able to differential normal from pathological tissue and pathological tissue of different entities in this immediate ex vivo study. Unfortunately, OCT provided inadequate cellular and subcellular information to enable the grading of oral premalignant disorders. Conclusion: This study enabled the creation of OCT bank of normal and pathological oral tissues. The pathological changes identified using OCT enabled differentiation between normal and pathological tissues, and identification of different tissue pathologies. Further studies are required to assess the accuracy of OCT in identification of various pathological processes involving the oral tissues.

Substance P has been studied in relation to its distribution within gingival tissues as well as its effect on cultured human gingival fibroblasts. The tissue distribution was varied depending on the degree of inflammation present. In healthy tissues substance P was found in the connective tissues interspersed between the collagenous elements and was particularly prominent in the areas immediately subjacent to the epithelial rete pegs. In inflamed tissues, substance P was markedly increased particularly around the blood vessels as well as in close association with much of the inflammatory cell infiltrate. The effect of substance P on human gingival fibroblast proliferation was monitored by [3H]-thymidine incorporation and indicated substance P to be mitogenic for these cells at low concentrations (1 x 10(-9) M) and tended towards an inhibitory effect at higher concentrations (1 x 10(-4) M). Substance P did not have any effect on the release of either total proteins or proteoglycans into the culture medium. However, exposure of the cells to substance P did cause a greater accumulation of both total protein and proteoglycan with the cell layer material. These findings suggest a potential role for substance P on gingival tissues and in particular their resident fibroblastic cells and can therefore be used as a basis for more detailed studies into the relationship between neuropeptide release associated with neurogenic inflammation and periodontal pathology.

Fibroblasts from nifedipine-induced fibrotic gingiva (NFG) have been characterized with respect to several cellular functions which could contribute to the characteristic clinical overgrowth of the gingiva: collagen synthesis and breakdown, glycosaminoglycan production, fibronectin synthesis, and proliferation. Histologic examination of NFG tissue revealed a hyperplastic epithelium with elongated, branched rete pegs. The connective tissue consisted of densely-packed collagen fibers and numerous enlarged fibroblasts, as well as regions of thinner, disorganized collagen fibers in the vicinity of scattered inflammatory and mast cells. Results of in vitro experiments showed that the fibroblast strains from the fibrotic gingiva (NFG) produced significantly greater amounts of collagen and lower levels of collagenase activity when compared to age- and sex-matched normal human gingival fibroblast strains. The NFG fibroblasts did not produce significantly greater amounts of fibronectin, and their level of glycosaminoglycan production was less than that of the normal fibroblasts. The NFG fibroblasts did not proliferate significantly more rapidly than the normal fibroblast strains. These findings therefore show that there are defects in the regulation of collagen production by NFG fibroblasts in vitro, and suggest that these alterations in collagen metabolism contribute to the over-deposition of collagen in this tissue, rather than hyperproliferation of the fibroblasts or through the production of increased amounts of fibronectin and glycosaminoglycans.

The cytolethal distending toxin (Cdt), expressed by the periodontal pathogen Aggregatibacter actinomycetemcomitans, inhibits the proliferation of cultured epithelial cells by arresting the cell cycle. The gingival epithelium is an early line of defense against microbial assault. When damaged, bacteria collectively gain entry into underlying connective tissue where microbial products can affect infiltrating inflammatory cells, leading to the destruction of the attachment apparatus. Histological evaluation of rat and healthy human gingival tissue exposed ex vivo to the Cdt for 36 and 18 hours, respectively, revealed extensive detachment of the keratinized outer layer and distention of spinous and basal cells in the oral epithelium. Treated human tissue also exhibited disruption of rete pegs and dissolution of cell junctions. Cells in the connective tissue appeared unaffected. Primary gingival epithelial cells, but not gingival fibroblasts, isolated from the same healthy human tissue were cell-cycle-arrested when treated with the toxin. These findings provide new evidence that the Cdt severely damages the oral epithelium, ex vivo, by specifically targeting epithelial cells, in situ. The Cdt shows preferential targeting of the epithelium as opposed to connective tissue in animal and human gingival explant models. Abbreviations: cytolethal distending toxin (Cdt), connective tissue (CT), 4′,6-diamidino-2-phenylindole (DAPI), human gingival epithelial cells (HGEC), human gingival explants (HGX), human gingival fibroblasts (HGF), junctional epithelium (JE), oral epithelium (OE), rete pegs (RP), sulcular epithelium (SE)

Gingival overgrowth tissues have thickened connective tissue stroma, sometimes accompanied by the increased presence of collagen fibers, thickened epithelia, and elongated rete pegs. We have previously shown that expression of CCN2, also known as connective tissue growth factor (CTGF), correlates positively with the degree of gingival fibrosis, and that markers of epithelial to mesenchymal transition (EMT) are characteristic of all drug-induced forms of gingival overgrowth. Here we experimentally evaluate whether increased degradation of the basement membrane and apparent invasion of the underlying stroma by epithelial cells could be observed in human gingival overgrowth tissues. Tissues from 20 different individuals with human gingival overgrowth and 15 non-overgrowth samples were evaluated by histological analyses and by immunohistochemistry assays of basement membrane proteins. The results demonstrate that there are significantly higher numbers of basement membrane discontinuities in overgrowth tissues, sometimes containing epithelial-like cells. Disrupted basal membrane structure in gingival overgrowth tissues is accompanied by a discontinuous collagen type IV expression pattern and decreased laminin 5. These findings provide new additional support for the hypothesis that epithelial plasticity and EMT promote gingival overgrowth, resulting in compromised basal membrane structure and increased interactions between epithelial and connective tissue layers that contribute to fibrotic pathology.

The aim of the present study was to compare periodontal healing after successive removal of periodontal tissue components, from the alveolar bone to the dentin surface. The prevailing tissue reaction when adhering PDM was left on the exposed roots was that most of the bone tissue that had been removed from the buccal surfaces had regenerated and the integrity of the PDM between the new alveolar bone and cementum surface had been reestablished. On exposed etched cementum surfaces, 2 prevailing healing results were recorded. In half the number of the roots, the root surfaces were covered by connective tissue with fibers running parallel to the root surfaces in a capsule-like arrangement. The other prevailing reaction was a thin epithelial cell-lining running parallel to the root surfaces in close contact or partly penetrating the adjacent connective tissue. On exposed denuded dentin surfaces, gingival retraction was a constant finding, associated with an epithelial cell-lining of varying thickness sometimes with rete pegs and cyst-like formations. Gingival retraction was also a constant finding on etched dentin surfaces. This was associated with pathological pockets outlined by epithelial cell-layers of varying thicknesses. The significance of these findings were discussed with special emphasis on dynamics of recurrent periodontitis.

The chronic usage of nifedipine is associated with the appearance of gingival overgrowth (GO). The frequency of GO associated with chronic nifedipine therapy remains controversial and the possible subclinical effects of this drug on the gingival epithelium should be investigated. We investigated the epithelial proliferation index and apoptosis rate, and their association with epithelial enlargement. Proliferation (Ki67 and Cyclin B1) and apoptosis (BCL2, Bax and p53) markers were identified by immunohistochemistry in twenty-one samples of gingival tissue from patients undergoing chronic treatment with nifedipine and in eleven samples of gingival tissue from healthy patients who did not use drugs associated with GO (control). Our results show that the epithelial tissue of nifedipine users has considerably longer rete pegs compared to control (P = 0.01). However, the density of Ki67(+) and Cyclin B1(+) cells was similar in both groups. Regarding apoptosis, we found more BCL2(+) cells in the nifedipine group when compared to controls (P = 0.12). An increase in Bax(+) cells in the nifedipine group compared to control (P = 0.003) was also seen, and slightly lower levels of p53(+) expression were observed (P = 0.51). Our results suggest that the chronic use of nifedipine is not associated with subclinical changes in gingival tissue.

Conspicuous facial pores are one type of serious esthetic defects for many women. We previously reported that the severity of impairment of skin architecture around facial pores correlates well with the appearance of facial pores in several ethnic groups. In our last report, we showed that serum levels of insulin-like growth factor-1 (IGF-1) correlate well with facial pore size and with the severity of impairment of epidermal architecture around facial pores. However, our results could not fully explain the implication between facial pores and IGF signaling. In this study, we conducted a histological analysis of facial skin to determine whether potential changes in IGF-1 availability occur in the skin with or without conspicuous pores. Immunohistochemical observations showed that expression of insulin-like growth factor binding protein-3 (IGFBP-3) is limited to the suprapapillary epidermis around facial pores and to basal cells of rete pegs without tips in epidermis with conspicuous pores. In contrast, in basal cells of skin without conspicuous pores, IGFBP-3 expression is very low. Ki-67 and IGF-1 receptor-positive cells are abundant in basal cells in the tips of the rete pegs in skin with typical epidermal architecture around facial pores. No obvious differences were observed in the expression of filaggrin, involucrin, K1, K6 or K17 in skin with or without conspicuous pores. However, increased expression of K16 was observed in skin with conspicuous pores suggesting hyperproliferation. These results suggest that the IGF-1/IGFBP-3 signaling pathway is involved in the formation of conspicuous facial pores due to the epidermal architecture around facial pores.

To assess the distribution pattern of Langerhans cells (LC) in normal porcine skin, epidermal sheets from six anatomical sites from three age-matched groups of male and female pigs were stained for ATPase activity. This histoenzymological technique is considered specific for Langerhans cells in normal epidermis. No statistically significant differences were observed between mean Langerhans cell density per mm2 of epidermis from male and female pigs, nor between different anatomical sites in the same age group. Statistically significant differences (P less than 0.0005) were observed when comparing group A one- to two-week-old piglets (463 to 518 LC mm-2) with group B six month olds (641 to 804 LC mm-2) and group C two years and over sows (741 to 830 LC mm-2). Morphological variations in the skin of young piglets, much thinner and with rudimentary or no epidermal rete pegs, could account for this significant variation.

Sir, Lichen nitidus was first described by Pinkus in 1901. It is an uncommon, chronic, papulosquamous eruption characterized by multiple, 1–2 mm, flesh-colored, shiny, dome-shaped papules. Although asymptomatic, it may sometimes be associated with pruritus.1 It classically involves the genitalia, upper extremities, chest and abdomen; in rare instances, it may become generalized.2 There appears to be no obvious racial or sex predilection; however, majority of cases are found in children and young adults. We present a young girl with a 4-year history of unremitting generalized lichen nitidus. A 10-year-old girl presented with a 4-year history of an asymptomatic eruption that first appeared over the hands and upper extremities and gradually spread to involve the lower limbs and trunk. The patient was otherwise healthy, and there was no intake of any prior medications or a similar family history. Clinical examination revealed numerous 1–2 mm shiny and skin-colored papules over the hands, forearms, feet, legs and abdomen, particularly around the umbilicus with multiple foci of koebnerization apparent on the forearms (Figs. ​(Figs.11–4). The face, oral mucosa, nails, palms, soles and anogenital area were not involved. Biopsy findings from one of the papules showed a focal granulomatous lymphohistiocytic infiltrate in the papillary dermis immediately subjacent to the epidermis clutched by the elongated rete pegs, thereby producing a “claw clutching a ball” picture. This confirmed the clinical diagnosis of lichen nitidus (Fig. 5). The patient was initially started on potent topical cortiscosteroids and was provided with the option of NB-UVB twice weekly; subsequently, she was lost for follow-up. Fig. 1 Skin-colored shiny papules on hands Fig. 4 Foci of koebnerization on forearm Fig. 2 Shiny papules on knees Fig. 3 Shiny papules on abdomen Generalized lichen nitidus is quite rare in children.3 In addition, several other uncommon variants that have been described include confluent, vesicular, hemorrhagic, familial, palmar and plantar, follicular, perforating and linear forms. Clinical instances of oral and nail involvement have also been reported in literature.4 The controversy regarding the etiology of lichen nitidus and its possible relationship to lichen planus is still unresolved. Some authors suggest that lichen nitidus represents a variant of lichen planus.5 Since lichen nitidus is usually asymptomatic and resolves without any sequelae, no treatment is required in most cases. However, the clinical course of generalized lichen nitidus is unpredictable with most patients experiencing spontaneous resolution several years after the onset of disease. Systemic and topical corticosteroids, dinitrochlorobenzene, diphenylcyclopropenone immunotherapy, astemizole, itraconazole, isoniazid, psoralen and ultraviolet A (PUVA) and narrow band ultraviolet B (NB-UVB) phototherapy have all been tried in its treatment, with PUVA, NB-UVB and astemizole being especially useful for generalized forms.6

Publisher Summary Data regarding age-related changes in skin structure and function are often conflicting and difficult to interpret. Multiple studies of blood flow present multiple conclusions. However, quantitative measurements permitted by bioengineering have allowed us to objectively and precisely study aging skin. Aging presents retraction of rete pegs and flattening of the epidermal-dermal junction. The anatomic facets of skin are infinite, making a complete review of age-related changes in skin structure problematic. This chapter focuses on certain readily quantifiable aspects of skin: blood perfusion, pH, thickness of strata, protein, glycosaminoglycan, water, and lipid content. Skin's acidity, an important part of the skin surface ecosystem and a contributor to defense against microbiological or chemical insults, plays a role in skin barrier homeostasis and stratum corneum desquamation. Collagen, which comprises approximately 70–80% of the dry weight of the dermis, is primarily responsible for skin's tensile strength. Collagen becomes less soluble, thinner, and sparser in intrinsically aged skin, but is thickened, fragmented, and more soluble with photoaging. Elastin is a long-lived protein in human skin; it appears to accumulate damage with age and sun-exposure. New elastin is synthesized in greater quantities in aged skin. The abnormal structure of this elastin prevents it from functioning as it does in young skin.

Verruciform xanthomas occur on mucocutaneous surfaces and are characterized by hyperkeratosis, acanthosis, and the occurrence of "foam cells" stuffed with lipid surrounding capillaries in the dermis between rete pegs. Ultrastructural examination of a lesion on the penis revealed the presence of melanocytes with many lipid droplets in the basal layer of the epidermis. We suggest that they are a major source of the lipid of the "foam cells." However, this study provides no information as to the nature or lineage of the "foam cells."

The purpose of this study was to examine the dermal and epidermal alterations associated with wound healing in wounds treated with papain urea copper chlorophyllin (PUC), papain-urea, copper chlorophyllin, or urea base ointment and compare these with moist wound care using a porcine full-thickness infected wound model. All the wounds were evaluated postsurgery for erythema, transepidermal water loss, microscopic morphology, and changes in protein expression. Examination of stained paraffin sections revealed an increase in the number of keratinocytes present in the epidermis of the PUC and papain-treated pigs, relative to moist control. This increase in keratinocyte number corresponded to an increase in the movement of the keratinocytes into the underlying dermis in the form of rete pegs. In the dermis, there appeared to be an increase in blood vessel formation, collagen I deposition, and mature collagen in the papain and PUC treated tissues. The quality of healing appears to be enhanced based on the number of keratinocytes present in the epidermis, the extensive rete peg formation, the increase in vasculature, and the increase in collagen birefringence.

Purpose: The Limbal Epithelial Crypt (LEC) is an anatomical structure that is found between the junction of the cornea and sclera and is in a unique position to make it an ideal structure to examine further. Previous studies have demonstrated the LEC to have properties that suggest it may be a stem cell niche. Basal cells of the LEC are significantly smaller than basal cells found in adjacent rete pegs, and morphologically they have a higher nuclear:cytoplasmic ratio. We set out to examine LEC further by exploring the surrounding LEC matrix proteins, and with known differentiation markers. Methods: Donated corneo-sclero rims were cut into eight equal sized pieces and frozen. Each piece was cut into 7μm serial sections, and was examined by microscopy for LEC structures. Identified LEC was collected on slides and stored until they were fixed in acetone and processed by standard immunofluorescence techniques for each differentiation marker. Results: Tenacin C was more positively taken up by the basement membrane of the LEC compared with the surrounding limbus. In addition, staining for desmoglein was negative against isolated small subpopulations of cells within the basal regions of the LEC. Conclusions: The LEC structure demonstrates properties that may identify this as a possible stem cell niche. Further studies are necessary to determine the significance of the LEC in its role in stem cell maintenance.

A 59-year-old woman presented with an itchy and uncomfortable raised lesion at a tattoo site (Fig. 1) on the lateral aspect of the left leg, just above the ankle. The tattoo had been placed 2 years before her presentation and the tattoo site was sun exposed. Immediately after she had the tattoo, she noticed redness of the skin. After a week, a pruritic and red scaly nodule developed that continued to gradually enlarge until her presentation. The patient had tried topical vitamin A and D ointment with no relief. The patient also had tattoos on the arms without any noticeable skin changes. The patient reported that the tattoo procedure on her leg was more painful than that on her arms, and was performed by a different (and perhaps inexperienced) tattoo artist. The original tattoo contained red, green, and yellow pigments. Figure 1. Raised nodular lesion with irregular margins A diagnosis of tattoo granuloma was considered; squamous cell carcinoma and fungal infection were included in the differential diagnosis. A punch biopsy was performed, followed by complete surgical excision of the lesion with a split-thickness skin graft from the right thigh. The skin excision specimen showed a 3 × 2.5-cm granular and pitted pink lesion with well-demarcated, somewhat irregular borders. The lesion was raised 0.5 cm above the skin surface. The lesion was present in the center of the original tattoo. Portions of the original tattoo with green and blue–green pigmentation were visible on either side of the lesion. No satellite lesions were identified. Microscopically, the raised lesion demonstrated striking pseudoepitheliomatous hyperplasia, with irregular acanthosis of the epidermis and follicular infundibula, hyperkeratosis, and parakeratosis (Fig. 2). Follicular plugging was present with keratin-filled cystic spaces. There was a brisk mononuclear inflammatory infiltrate in the dermis, composed primarily of lymphocytes, with admixed plasma cells and histiocytes. Giant cells were occasionally identified. Dermal pigment deposition was noted both within the lesion and in the surrounding skin, corresponding to the original tattoo. Variable dermal fibrosis was noted, with thick collagen bundles in some areas. There was no evidence of epidermal keratinocytic atypia, dyskeratosis, or increased suprabasal mitotic activity. Special stains (periodic acid–Schiff and acid-fast) for microorganisms were negative. Figure 2. (a) Raised lesion with marked pseudoepitheliomatous hyperplasia and follicular plugging (hematoxylin and eosin; magnification, ×2.5). (b) Irregularly elongated and thickened rete pegs with blunt ends associated with dermal chronic inflammation (hematoxylin and eosin; magnification, ×5). (c) Follicular dilation and plugging with keratin-filled cystic spaces (hematoxylin and eosin; magnification, ×5). (d) Dermal pigment and fibrosis (hematoxylin and eosin; magnification, ×10)

Diagnosis of periodontal disease, a frequent disorder in dogs, rests mainly upon the assessment of changes affecting the gingiva. Loss of gingival stippling, one of the early symptoms of periodontal disease in the human, could also indicate early periodontitis in the dog. The aim of this study was to determine the presence of gingival stippling in dogs, its location on alveolar processes, its association with age and inflammation, and its relation to the microstructure of the gingiva. The study concerns clinical, scanning electron and light microscopic examination of the gingiva of 48 dogs. Stippling, i.e. the granular appearance of the gingiva resembling irregularly distributed crater-like depressions of varying sizes, was present in adult but absent in young and senescent dogs. Stippling was most prominent at the level of the canine and the carnassial teeth. In contrast to the human gingiva, depressions and elevations of the stippled gingiva of the dog were not distributed uniformly. Presence of stippling indicates the presence of well developed mucosal layers and extensive interdigitation of epithelial rete pegs and papillary layer. Interaction of inelastic collagen fibres and a high hyaluronan content within papillary layer resulting in a high turgor of tissue due to the extensive water binding capacity of hyaluronic acid could also play a role in shaping of the gingival surface. The significance of gingival stippling in the diagnosis of periodontal disease in dogs is limited, as stippling occurs in healthy but also slightly inflamed attached gingiva of adult individuals.

Background: Clinical and histomorphological features of psoriasis and its close mimickers have many overlapping features. The diagnostic differentiation of psoriasis from other psoriasiform eruptions enables treatment as per the extent of eruptions and modified according to the tissues involved and associated co morbidities. Morphometric analysis of histopathological features may help to alleviate this dilemma. Aim: This study attempts to evaluate the morphometric measurements using eye-piece micrometer in differentiating psoriasis from psoriaform dermatitis. Materials and Methods: The 50 cases, 25 each of clinically and histologically confirmed cases of psoriasis and psoriasiform dermatitis were compared by using measurable morphometric parameters. The results were statistically analyzed for significance. Results: Length of rete pegs, length of dermal papillae and the ratio of length/average width of rete pegs showed statistically significant increase in psoriasis when compared to psoriaform dermatitis. Suprapapillary thickness had less significance. Some other important histomorphological parameters were also compared. Conclusion: The length of rete pegs, the length of dermal papillae and the ratio of length/average width of rete pegs are statistically more significant in the diagnosis of psoriasis when compared to psoriasiform dermatitis.

Nifedipine is used as a long-acting vasodilator; one of its side effects is gingival overgrowth, characterized by an accumulation of collagenous components within the gingival connective tissue and epithelial hyperplasia with elongated, branched rete pegs penetrating into the connective tissue. We investigated the effect of nifedipine on apoptosis of gingival keratinocytes of rats to elucidate the mechanism of nifedipine-induced gingival epithelial hyperplasia.Twenty-day-old rats were fed a powdered diet containing or lacking nifedipine for 8 to 30 days. The mandibular gingiva and palatal mucosa were removed on days 8, 15, or 30, and epithelial thickness was examined by light microscopy. In situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was used to examine apoptosis of keratinocytes in the epithelium. In addition, we examined the effects of nifedipine on proliferation of keratinocytes and epithelial cell life on day 8 by 5-bromo-2'-deoxyuridine (BrdU) staining.Microscopic examination showed gingival epithelial hyperplasia in nifedipine-treated rats after day 15. Apoptosis of gingival keratinocytes was seen to be inhibited in nifedipine-treated rats on day 8 and 15. Also, nifedipine did not induce an increase of keratinocyte proliferation activity in terms of the number of cells showing positive staining with BrdU. Prolongation of cell life by nifedipine was observed on day 8 in gingival epithelium through a delay of upward cell movement compared to controls. However, epithelial hyperplasia was not detected in palatal mucosa, and there were no significant differences in apoptotic rates of keratinocytes and cell life between nifedipine-treated rats and control rats.These results suggest that nifedipine induces epithelial hyperplasia in gingival overgrowth not by an increase in keratinocyte proliferation, but by prolongation of cell life through reduction of apoptosis before epithelial hyperplasia is detectable.

Background. Microdermabrasion has become a popular method of skin rejuvenation for treating dyschromia, fine wrinkles, and mild scarring. Objective. To analyze the onset and extent of the dermatologic changes associated with microdermabrasion. Methods. Ten volunteers, ages 31–62 years, underwent a series of six aluminum oxide microdermabrasion facial treatments 7–10 days apart. Skin biopsy specimens were obtained prior to the study, after three treatments, and after six treatments. Results. Compared to the controls, the treated areas demonstrated the following histologic changes: thickening of the epidermis and dermis, flattening of the rete pegs, vascular ectasia and perivascular inflammation, and hyalinization of the papillary dermis with newly deposited collagen and elastic fibers. Conclusion. This study suggests that microdermabrasion produces clinical improvement by a mechanism resembling a reparative process at the dermal and epidermal levels.

Hyperplastic gingival tissues show the histopathological characteristics of thick parakeratinized squamous epithelia with acanthosis and rete pegs elongated into the lamina propria. However, the pathogenic factors that contribute to the epithelial morphogenesis of this disease are obscure and remain to be studied.We immunohistochemically examined the expression of both c-Myc and bcl-2 oncoprotein, which can exert influence on the epithelial morphogenesis and homeostasis, in 12 hyperplastic gingival tissues induced by nifedipine and phenytoin as well as 5 control tissues using avidin-biotin-peroxidase complex methods.Four specimens out of 5 nifedipine-induced and 5 out of 7 phenytoin-induced hyperplastic gingival tissues revealed the expression of c-Myc oncoprotein, whereas no significant immunostaining of c-Myc oncoprotein was found in 5 control tissues. The c-Myc oncoprotein-positive cells were observed to be localized in the basal and suprabasal cell layers of the hyperplastic gingival epithelia. Although all of the 12 hyperplastic gingival epithelia showed the distribution of bcl-2 oncoprotein in the basal and suprabasal layer cells, in 5 control epithelia the bcl-2 oncoprotein expression was slight and confined to the basal layer cells.The results of our present study indicate that the synergistic overexpression of c-Myc and bcl-2 oncoprotein may be related to the pathogenesis of gingival hyperplasia induced by nifedipine and phenytoin, especially to the morphogenesis of hyperplastic epithelia.

Accumulating evidence has emphasized the importance of immunocompetent cells in determining the psoriatic phenotype. We have investigated the effect of 1alpha,25-dihydroxycholecalciferol, the naturally occurring active form of vitamin D3, cyclosporine A, and interleukin-10 on the phenotype of human psoriatic skin xenotransplants. First, psoriatic skin transplants were injected with either 1alpha,25-dihydroxy- cholecalciferol, cyclosporine A, or interleukin-10. Second, we determined the ability of autologous lymphocytes, activated in vitro using staphylococcal enterotoxin B and interleukin-2 and then exposed to either 1alpha, 25-dihydroxycholecalciferol or cyclosporine A, to induce psoriatic lesions if they were injected into the dermis of uninvolved skin grafts. We found that injections into transplanted psoriatic plaques of either 1alpha,25-dihydroxycholecalciferol or cyclosporine A, but not interleukin-10, resulted in a consistent reduction in the clinical and histologic score of psoriasis with remission towards uninvolved psoriatic skin. Injection of activated immunocytes into symptomless psoriatic skin grafts, changed the grafts towards plaque-type psoriasis with silvery scale, parakeratosis, elongated rete pegs, acanthosis, and dermal angiogenic reaction. In contrast, if activated immunocytes were exposed to 1alpha, 25-dihydroxycholecalciferol or cyclosporine A prior to injection, only minimal changes occurred. It was determined that neither staphylococcal enterotoxin B and interleukin-2 activation by itself, nor the drugs investigated, changed the CD4/CD8 ratio of activated (CD25 + ) cells. Our results are consistent with the hypothesis that psoriasis may be induced by activated T lymphocytes, and indicate that novel immunomodulatory drugs can serve to inhibit the pathogenetic ability of immunocytes in psoriasis.

To clarify the possible pathophysiological role of medullasin, a neutrophil elastase-like proteinase, in nifedipine (NF)-induced gingival overgrowth, a rat model of gingival overgrowth was first established using a diet containing NF. The relation between histopathological changes and the distribution of the proteinase was then investigated. Thirty-two, specific pathogen-free 20 day-old, male, Fisher 344 rats were fed a diet containing NF and killed at 2, 8, 16 and 32 weeks. Control rats (n=32) were fed the same diet but without the drug. The mandible of each rat was resected and sectioned at 4-μm thickness buccolingually between the first and second molars. Computer image analysis was used to evaluate the extent of overgrowth in the approximal gingiva of each sample. To examine medullasin activity, the mean percentage of medullasin-positive cells per total cells counted in the pocket epithelium and the connective tissue adjacent to the epithelium of approximal gingiva was determined immunohistochemically. The height of the mid-portion and the area in NF-treated group increased significantly with time (with the exception of area at 2 weeks) compared with the corresponding regions in the control group. A marked inflammatory-cell infiltration and elongated rete pegs, especially in the mid-portion of approximal gingiva, were seen in the NF-treated group. The mean percentages of medullasin-positive cells in the NF-treated group at 8, 16 and 32 weeks were significantly higher than those of the control. Although medullasin-positive cells were mainly neutrophils, in several samples of the NF-treated group they were recognized as macrophage-like. These findings suggest that medullasin may be involved in host defence and immunoregulation in a NF-induced rat model of gingival overgrowth.

In the present study we examined whether an acute infusion of HCI into the esophagus of rabbits would cause an increase in esophageal cellular proliferation independent of morphologic evidence of cell injury. To examine this question, the distal two thirds of the rabbit esophagus was infused for 1 hour with either 40 mmol/L HCI or NSS (control), and cellular proliferation was studied 24 and 48 hours later by using bromodeoxyuridine (BrDu) to label the nuclei of dividing cells and ornithine decarboxylase (ODC) enzyme activity as a biochemical index of cell division. Although there was no gross or microscopic evidence of cell necrosis or mucosal inflammation 24 hours after H + infusion, BrDu labeling of basal cell nuclei was significantly greater 24 hours after H + infusion (31% ± 6%) as compared with that in control animals infused with NSS (15% ± 4%). This increase in labeling index was paralleled by a threefold greater ODC enzyme activity at 24 hours with H + infusion. Rete pegs were infrequent in control tissues (4 ± 4 rete pegs per 100 μm of esophageal length) or in animals examined 24 hours after acid exposure (4 ± 2 rete pegs per 100 μm). However, rete pegs were very prominent 48 hours after acid infusion (22 ± 6 rete pegs per 100 μm). A short exposure to acid can cause a significant increase in mucosal proliferation independent of injury, suggesting that esophageal cell acidification either directly or indirectly acts as a tissue mitogen.