Enhancement of transmucosal permeation of cyclosporine by benzalkonium chloride.

OBJECTIVES: Permeation of cyclosporin A (CsA) through intact and de-epithelialized human vaginal mucosa in the presence and absence of benzalkonium chloride (BZCl) was tested. MATERIALS AND METHODS: Human vaginal mucosa (snap-frozen in liquid nitrogen, stored at -85 degrees C) had been used for permeability experiments. CsA permeation through thawed frozen intact and de-epithelialized vaginal mucosa was determined using a flow-through diffusion apparatus (20 degrees C, 24 h). Flux rates for CsA across these two mucosae were determined in the presence and absence of 0.01% BZCl. ANOVA and Duncan's multiple range test were used to test for steady-state and an unpaired t-test with Welch's correction was used to test for differences between the mean flux values at each time point (significance level of 5%). A piece of thawed tissue from each patient, before and after de-epithelialization, was placed in formalin and histologically examined. RESULTS: Flux rates of CsA across intact vaginal mucosa tended to increase by 28-46% in the presence of 0.01% BZCl, and CsA across de-epithelialized mucosa by approximately 28%. The latter differences were statistically significantly higher after 10 h. Flux rates across de-epithelialized mucosa were 52-140% higher in the presence of 0.01% BZCl (statistically significantly higher after 12 h). CONCLUSIONS: The permeation of CsA through intact and de-epithelialized human vaginal mucosa can be enhanced by 0.01% BZCl.

A comparative light-microscopic, electron-microscopic and chemical study of human vaginal and buccal epithelium.

The scarcity of sizeable specimens of normal oral mucosa for experimental purposes has hampered research on oral epithelium. Because large specimens of viable human vaginal mucosa are readily available and because vaginal and buccal epithelia are microscopically similar, vaginal mucosa has been used successfully to establish a human cyst model in experimental animals. The ultrastructure and distribution of keratin filaments in these epithelia are also similar, as is their permeability to water and a number of chemical substances. Therefore, if vaginal mucosa could be substituted for buccal mucosa it would expedite research on the epithelium of buccal mucosa. To strengthen further the concept that vaginal epithelium could replace buccal epithelium in certain experimental studies, the thickness of these epithelia, their patterns of surface keratinization, the presence or absence of intercellular lipid lamellae and their lipid contents were now compared. Thirty-three specimens of vaginal mucosa from postmenopausal women and 36 of buccal mucosa were investigated. To compare the thickness of the epithelial layers the number of cell layers in sections of 20 vaginal and 20 buccal mucosal specimens were counted in the three thickest and three thinnest regions of each specimen. Surface keratinization was evaluated on sections stained with the Picro-Mallory method. To demonstrate lipid lamellae two vaginal and two buccal mucosa specimens were examined electron microscopically after normal fixation and postfixation in ruthenium tetroxide. Following solvent extraction of 11 vaginal and 14 buccal epithelia, quantitative lipid analyses were performed using thin-layer chromatography. No statistically significant differences were found between the maximum and minimum number of epithelial cell layers. The patterns of surface keratinization and the distribution and appearance of the lipid lamellae in the intercellular spaces were similar. The lipid composition of the two epithelia corresponded, except for the cholesterol esters and glycosylceramides, which were higher in buccal epithelium. Ceramides for vaginal epithelium and triglycerides for buccal epithelium were not determined. Based on structural similarities, a similar lipid composition and earlier findings, it is concluded that vaginal epithelium can be used as a substitute for buccal epithelium in certain in vitro, and possibly for in vivo, studies.

Hemangiomatous ameloblastoma: Clinical, radiologic, and pathologic features.

A hemangiomatous ameloblastoma was present in the third molar region of the left mandible of a 26-year-old woman. The histology and radiologic features of this tumor differed from those of a conventional ameloblastoma. Its histologic features were consistent with those of a hemangiomatous ameloblastoma, and its standard radiologic features and computed tomography mimicked that of fibro-osseous lesions, whereas magnetic resonance imaging suggested a vascular lesion. The behavior and prognosis of the hemangiomatous ameloblastoma are uncertain because of the small number of documented cases and lack of long-term follow-up, but are thought to be similar to those of the conventional type. The relevant clinical, radiologic, and pathologic features of this case are presented.

Human vaginal epithelium and the epithelial lining of a cyst model constructed from it: a comparative light microscopic and electron microscopic study.

The light microscopic features and keratin filament distribution of human vaginal epithelium resemble those of buccal mucosa. We used vaginal epithelium to establish a human cyst model in immunodeficient mice. To strengthen the view that this experimental cyst is a suitable model to study mucosal diseases, we compared specific light microscopic and ultra-structural features of vaginal epithelium and the epithelial lining of the cyst. Nineteen cyst walls and 6 specimens of vaginal mucosa, which had been used to establish the cysts, were examined. We counted the number of cell layers of 17 cyst linings and the 6 vaginal specimens. Surface keratinisation was evaluated on sections stained with the Picro-Mallory method. To demonstrate intercellular lamellae and membrane coating granules 2 cyst linings were examined ultra-structurally. The epithelium lining of the cyst wall was thinner than that of vaginal mucosa but the surface keratinisation and ultra-structural features of the intercellular lamellae and membrane coating granules were similar. We concluded that vaginal mucosa is a useful substitute for oral mucosa in the cyst model.

Non-Hodgkin's lymphomas of Waldeyer's ring: a clinicopathological and immunological study of 64 cases in the western Cape.

The clinicopathological and immunological features of 64 cases of primary extranodal non-Hodgkin's lymphoma (NHLs) that occurred in Waldeyer's ring (WR) were examined. The objective was to compare the findings of this study with those of previous studies. The age at presentation, sex ratio, and site of occurrence of these tumours within WR concurred with that of other studies. Diffuse large cell lymphomas were the most prevalent in this study. Most T-cell NHLs occurred in the nasopharynx where they constituted 28% of all NHLs in that site. This indicates a higher incidence of nasopharyngeal T-cell NHLs in South Africa as compared with other Western countries.

Permeability of vaginal mucosa to water at normal and elevated temperatures.

A number of studies have clearly demonstrated that human vaginal mucosa may be used as a model of buccal mucosa for a variety of in vitro permeability studies on drugs and other chemical compounds. Furthermore, at between 25 degrees and 37 degrees C, a linear temperature-dependence of water flux across this mucosa, which was attributed to an increased fluidity of the principal lipoidal permeability barrier, was found to exist. The objective of the present study was to examine the behaviour of the above barrier on water fluxes at normal and elevated temperatures. Clinically healthy human vaginal mucosa specimens were obtained from excess tissue removed during a vaginal hysterectomy from a single patient, snap-frozen in liquid nitrogen and stored for 6 months at -85 degrees C. Seven sections from the mucosa were thawed in phosphate-buffered saline (PBS) and mounted in flow-through diffusion cells (exposed area 0.039 cm2). Their permeability to tritiated water was determined using a continuous flow-through perfusion system at temperatures of 37 degrees, 39 degrees and 41 degrees C. Three permeability experiments were performed at each temperature setting. Specimens were subjected to histological examination before and after permeability experiments. Mean water flux rates at steady state (10-24 h) were found to be 2,356 +/- 71 SEM, 3,020 +/- 38 SEM and 3,659 +/- 116 SEM cpm. cm-2.min-1, at temperatures of 37 degrees, 39 degrees and 41 degrees C, respectively. A linear regression analysis and plot (r2 = 0.99) displayed a slope of 325 +/- 4 SEM cpm.cm-2.min-1/degree C. The results of this study showed that, notwithstanding cellular damage, the principal physical permeability barrier was linearly temperature-dependent between the temperatures studied, providing further support for the concept that this barrier is lipoidal in nature.

Diffusion rates of vasopressin through human vaginal and buccal mucosa.

The permeability to several chemical compounds and the histology of vaginal and buccal mucosa are very similar. Because vaginal mucosa is more abundant, it may be used as a model for the latter. To further develop the vaginal/buccal mucosa model, the objective of the present study was to evaluate the passage of a small polypeptide, vasopressin, across fresh and frozen specimens of these two mucosae. Specimens of fresh buccal and vaginal mucosa were taken from excised tissue obtained following vaginal hysterectomies and various oral surgical procedures. Pieces of buccal and vaginal tissue specimens obtained were used fresh or were snap-frozen and stored at -85 degrees C for periods of up to 10 months. Biopsies from fresh and thawed specimens were mounted in flow-through diffusion cells and their permeability to tritiated vasopressin was determined using a continuous flow-through perfusion system. Specimens were examined histologically before and after freezing as well as before and after permeability experiments and similarities between vaginal and buccal tissues verified. No statistically significant differences between flux values for fresh and frozen vaginal and buccal mucosa, respectively, were found. These results demonstrate that the permeation of vasopressin across fresh and frozen human vaginal and buccal mucosa is for practical purposes similar. These results further support the human vaginal/buccal mucosa model for in vitro permeability studies on therapeutically active compounds.

Penetration of human vaginal and buccal mucosa by 4.4-kd and 12-kd fluorescein-isothiocyanate-labeled dextrans.

In a previous study we demonstrated that human vaginal mucosa was as permeable to water as was buccal mucosa. Water, however, is a very small molecule with a molecular weight of 18 d. To further explore similarities between these two types of mucosa with respect to permeability, it was decided to investigate the passage of two large, hydrophilic molecules across these epithelia. Specimens of fresh, clinically healthy human vaginal and buccal mucosa were taken from excised tissue obtained during vaginal hysterectomies and various oral surgical procedures. Seven biopsy materials from each specimen were mounted in flow-through diffusion cells (exposed area, 0.039 cm2), and their permeability to 4.4- and 12-kd fluorescein-isothiocyanate-labeled dextrans was determined through use of a continuous flow-through perfusion system. Dextran was detected by means of a fluorospectrophotometric method at excitation and emission wave lengths of 498 and 520 nm, respectively. Specimens were examined histologically before and after permeability experiments, and similarities between vaginal and buccal tissues were verified. No statistically significant differences between the flux values of the 4.4-kd dextran across vaginal and buccal mucosa were found. However, for the 12-kd dextran the flux rate across buccal mucosa was significantly higher than the rate across vaginal mucosa. These results demonstrate that human vaginal mucosa is for practical purposes as permeable as buccal mucosa to 4.4-kd hydrophilic molecules. This further supports the hypothesis that vaginal mucosa may be a useful model for studying the passage across buccal mucosa of chemical compounds and therapeutic agents that are less than approximately 4.4 kd in molecular mass. For a 12-kd dextran the flux rate across buccal mucosa is significantly higher than the flux rate across vaginal mucosa, and the model becomes inaccurate.

Permeation of 17beta-estradiol through human vaginal and buccal mucosa.

Because of the relative scarcity of fresh human oral mucosa specimens for permeability studies, we investigated the use of human vaginal mucosa as a model of the former. In a previous study we demonstrated the comparable diffusion rate of water across human vaginal and buccal mucosa and proposed the use of the former as a suitable model of the latter for in vitro drug permeability studies. To further evaluate the human vaginal/buccal mucosa model, we decided to compare these two tissues with respect to their permeability to 17beta-estradiol. Clinically healthy human vaginal and buccal mucosa specimens were obtained during vaginal hysterectomies and different oral surgical procedures. The permeability of each tissue specimen to 17beta-estradiol was determined through the use of a continuous flow-through diffusion system. Specimens were examined histologically before and after experiments. Mean flux values for 17beta-estradiol across human buccal mucosa tended to be slightly higher than those observed for vaginal tissue, but no statistically significant differences could be demonstrated. The results from this study further support our hypothesis that human vaginal mucosa may be a suitable model of human buccal mucosa for in vitro drug permeability studies.

Central calcifying odontogenic cyst. A review of the literature and the role of advanced imaging techniques.

The central calcifying odontogenic cyst (CCOC) is a rare lesion. This paper reports a new case, reviews the clinical, histomorphological and radiographic features reported in the literature and describes the CT and MRI features of this new case. We postulate that, as part of an evolutionary process, cystic COCs originate as unilocular lesions but may later become multilocular. The role of advanced imaging and histology in the diagnostic process are discussed.

Permeability of lichen planus lesions and healthy buccal mucosa to water.

The resurgence of interest in the oral mucosa as a route for drug delivery requires a thorough understanding of the permeability of this tissue in health and disease. Previous work has indicated that non-keratinized oral mucosa is more permeable than its keratinized counterpart. It has been suggested that pathological hyperkeratotic mucosa, which was previously non-keratinized, would be more permeable than healthy tissue. Equivocal results obtained from animal studies in which chemical or mechanical irritation was used to induce a hyperplastic and hyperkeratotic epithelium, prompted us to conduct a study on the comparison of the permeability to water of lichen planus lesions and healthy buccal mucosa. Buccal mucosa was obtained from six patients with previously confirmed lichen planus and from six clinically healthy patients. Thawed biopsies from each specimen were mounted in flow-through diffusion cells and their permeability to tritiated water determined using a continuous flow-through perfusion system. Specimens were examined histologically before and after permeability experiments. No statistically significant differences between mean steady state flux values (10-20 h) for lichen planus tissue and healthy buccal mucosa were found. These results warrant further studies with other oral conditions associated with hyperkeratosis to establish whether the nature and course of the condition are determinants for the retention or loss of the epithelium's permeability characteristics.

Effect of temperature on permeability of mucosa to water.

In previous studies it has been demonstrated that frozen human vaginal mucosa can be used as a model of buccal mucosa for in vitro permeability studies on a variety of chemical compounds, including drugs. However, most of the latter studies have, for the sake of convenience, been conducted at room temperature (+/- 20 degrees C). The objective of the present study was to determine the effects of increased temperature on steady state flux rates of water through vaginal mucosa. Specimens of clinically healthy human vaginal mucosa were obtained from excess tissue removed during a vaginal hysterectomy from a single patient, snap-frozen in liquid nitrogen at -85 degrees C and banked for 8 months. After thawing in PBS buffer, seven sections from the vaginal mucosa were mounted in flow-through diffusion cells (exposed area 0.039 cm2) and their permeability to tritiated water determined using a continuous flow-through perfusion system at temperatures of 25 degrees, 30 degrees and 37 degrees C. Permeability experiments were performed in triplicate at each temperature setting. Specimens were examined histologically before and after permeability experiments. Mean water flux rates at steady state (16-24 h) were found to be 1760 +/- 22 SEM, 2623 +/- 63 SEM and 4155 +/- 70 SEM cpm. cm-2.min-1, at temperatures of 25 degrees, 30 degrees and 37 degrees C, respectively. A linear regression analysis and plot (r2 = 0.99) displayed a slope of 200 +/- 13 SEM cpm. cm-2.min-1/degree C. The results of this study clearly demonstrated the temperature-dependency of flux rates of water across vaginal mucosa, and this should be taken into account whenever the in vitro vaginal/buccal model is used at room temperature for predicting in vivo buccal drug absorption kinetics.

Mandibular infected buccal cyst and paradental cyst: the same or separate entities?

The WHO classification of odontogenic cysts includes the radicular (residual) and paradental (inflammatory collateral; mandibular infected buccal) cysts as inflammatory odontogenic cysts. Because the paradental group of inflammatory cysts may clinically cause diagnostic and therapeutic problems when they are associated with first and second molar teeth it was decided to review the literature and present an additional case. The aetiology and histological features of the inflammatory collateral cyst, the paradental cyst and the mandibular infected buccal cyst are identical and the differences that exist in their clinical and radiological presentation can be related to the different teeth that are involved and the difference in the ages at which these teeth erupt. These cysts represent the same entity and their treatment is dependent on the tooth involved. With the aid of magnetic resonance imaging (MRI) the distinction between a paradental cyst on the buccal aspect of a molar tooth and a periodontitis can be made.

Comparative permeability of human vaginal and buccal mucosa to water.

There is currently a resurgence of interest in the oral mucosa as a route for drug delivery. The relative scarcity of human oral mucosa for in vitro permeability studies, and the fact that vaginal mucosa is histologically similar and more abundant than the former, caused us to compare these 2 tissues with respect to their barrier properties to water. Specimens of fresh, clinically-healthy human vaginal and buccal mucosa from non-smokers were taken from excised tissue obtained during vaginal hysterectomies and various oral surgical procedures. Biopsies from each specimen were mounted in flow-through diffusion cells and their permeability to tritiated water determined using a continuous flow-through perfusion system. Specimens were examined histologically before and after permeability experiments and similarities between vaginal and buccal tissues verified. No statistically significant differences between mean steady state flux values (10-16 h) for vaginal and buccal mucosa, respectively, were found. Human vaginal mucosa is therefore as permeable as buccal mucosa to water, and these results warrant further investigation with other compounds to establish whether vaginal mucosa may be a useful model for buccal mucosa for drug permeability studies.

An experimental cyst model established from human unkeratinized vaginal mucosa.

Because of the scarcity of sizeable specimens of normal oral mucosa and the availability of human vaginal mucosa, which resembles the lining mucosa of the mouth, we used the latter to establish a human cyst model. Fragments of vaginal mucosa, removed during corrective procedures, were sutured around 2 mm glass balls and implanted into the flanks of nude mice. Thirty-seven specimens were implanted and 31 harvested after 3, 6, 9 and 12 weeks. At 6 weeks the wall of the implanted cyst consisted of recognizable unkeratinized vaginal mucosa but had not healed completely at the sutured edges. From 9 weeks the cyst cavities were healed and the lumens lined by unkeratinized stratified squamous vaginal epithelium. The enclosing connective tissue had retained the characteristics of the lamina propria of the vaginal mucosa and could be distinguished from mouse tissue.

Case report. Magnetic resonance features of metastatic melanoma of the temporomandibular joint and mandible.

We report a case of histologically verified melanoma of the nose which presented 2 years after initial radiotherapy with left temporomandibular pain, dysfunction and dental sepsis. Conventional radiography revealed a partially dentate mandible with a destructive lesion involving the left condyle, an ill-defined lesion in the right retromolar region and chronic inflammatory apical root lesions. Since MRI of the nose was done at the initial presentation, it was postulated that MRI could be used to characterize the destructive jaw lesions. The MR features were similar to the original nasal lesion and accepted as proof of diagnosis of metastatic melanoma. A literature review reveals only 37 previous cases of metastasis to the temporomandibular joint with none of involvement by melanoma. The role of MRI in the diagnosis of this lesion is also described for the first time.

Desmoplastic ameloblastoma: correlative histopathology, radiology and CT-MR imaging.

A desmoplastic variant of ameloblastoma with osteoplasia in the stroma is reported. This tumour presented in the canine/premolar region of the left maxilla of a 31-year-old woman. It was treated by partial hemimaxillectomy and immediate reconstruction with a non-vascularised iliac graft. The location of this lesion, its histology and radiological features differ from those of the conventional ameloblastoma. The behaviour and prognosis of the desmoplastic ameloblastoma (DA) cannot at this stage be predicted due to the small number of cases that have been reported and a lack of long-term follow-up. To our knowledge this is the first documentation of the CT and MRI features of desmoplastic ameloblastoma with pathologic correlation.

Synovial chondromatosis: Report of a rare surgical problem of the temporomandibular joint.

Synovial chondromatosis of the joint is a rare benign condition characterized by the formation of metaplastic cartilage in the synovium of the joint resulting in numerous attached and unattached osteocartilagenous bodies. It may recur after surgical intervention. For this reason removal of the synovium and the bodies is advocated. This is a report of a case which occurred in the temporomandibular joint which had numerous loose bodies and exhibited features of degenerative joint disease as well. The loose bodies were removed, a high condylar shave performed and the synovium left intact. The patient is still free from joint problems five years later.

A bitemark case with a twist.

This is a case report in which the bite patterns of two suspects were compared to a bitemark on the breast of a murder victim. Each suspect had sufficient concordant features to have been found guilty of producing the bitemark. The irony in this case is that the bitemark was not inflicted by the murderer.