Dermal Zone Research Articles

Incorporation of suvorexant and lemborexant into hair and their distributions after a single intake.

This study examined the applicability of hair analysis as an approach to identify suvorexant (SUV) and lemborexant (LEM) intake by analyzing black hair specimens collected from study participants after a single oral administration. Hair specimens were collected form participants who took a single dose of 10 mg SUV or 5 mg LEM. Identification of the dual orexin receptor antagonists (DORAs) and their metabolites was performed by liquid chromatography-tandem mass spectrometry. Reference standards of S-M9 and L-M4, the metabolites of SUV and LEM, respectively, were synthesized in our laboratory. Sectional analysis of 1-mm segments of the single-hair strands was also performed to investigate the incorporation behavior of the drugs into hair. Unchanged SUV and LEM, and their metabolites S-M9 and L-M4 were detected even in the single-hair specimens. Results of the segmental hair analysis showed predominant incorporation of the drugs into hair through the hair bulb region rather than through the upper dermis zone of the hair root. The drug concentrations in the hair specimens, collected about 1month after intake, were 0.033-0.037pg/hair strand (0.17-0.19pg/mg) for SUV and 0.054-0.28pg/hair strand (0.28-1.5pg/mg) for LEM. The calculated distribution ratios of the DORAs into hair to the oral doses were much lower than those of benzodiazepines and zolpidem reported in a previous study. This is the first report of the detection of the DORAs in hair. The incorporation behavior of the DORAs into hair revealed herein are crucial for proper interpretation of hair test results.

Time course of estazolam in single-strand hair based on micro-segmental analysis after controlled oral administration.

The mechanism of estazolam incorporation into hair was investigated by studying the time course of estazolam along single-strand hair after two oral administration of estazolam at 28days interval. Estazolam in single hair segments 0.4mm in length was verified and quantified by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). The distributions of estazolam within a strand of hair (collected at 12h, 28days, and 56days post-administration) were visualized by micro-segmental analysis. The highest estazolam concentration (1.5-9.9pg/mm) was detected in the hair bulb region (S1), and it then decreased through the hair shaft to the distal end, with a small fluctuation (0.3-3pg/mm) near the junction of the hair roots and shafts (S4-S7) 12h after drug intake. These findings suggested that the incorporation of estazolam occurred in two regions, mainly in the hair bulb and to a lesser extent in the upper dermis zone. Models using internal temporal markers (TIMs) and temporal intervals (TIs) were constructed to estimate the day of estazolam ingestion. The estimation accuracy was within an average error of 1.7mm and 3.0mm between the calculated and actual positions, based on the TIMs and TIs 56days after estazolam intake. These findings can help in further elucidation of the drug incorporation mechanism, which is crucial for interpreting hair analysis results used to reveal individual drug-use history.

Содержание клеток в зонах дермы крыс в норме и на фоне метаболического синдрома при восстановлении после холодовой травмы

Local cold injury is not uncommon in areas with unfavourable climatic conditions. The significance of this problem is associated with a large number of such injuries, complexity of their treatment, long period of disability and high level of disablement among the population. Aggravating factors of cold injuries include metabolic abnormalities that can lead to the development of cardiovascular diseases, and, consequently, to microcirculation disorders. The aim of this paper was to trace the dynamics of the cellular structures of the dermis in the process of recovery from local cold injury in rats with metabolic syndrome, compared with the recovery process in healthy rats. Materials and methods. The study was conducted on outbred rats. The development of obesity and metabolic disorders was modelled by including a 30 % sucrose solution in the diet instead of water, as well as saturated fats. Local cold injury was modelled by applying a metal weight 2.5 cm in diameter cooled in liquid nitrogen to the depilated skin of the animals’ backs. Cell dynamics was studied in the papillary and reticular dermis as well as in the reticular dermis on the border with the hypoderm of the damaged area and on its periphery using a morphometric grid. Results. The data obtained suggest that regenerative changes after local cold injury in rats are associated with accumulation of cells on the border of the reticular dermis and the hypoderm of the damaged area. In addition, we observed a later onset of the peak of the migration process and a larger number of cells involved in migration at metabolic syndrome than during regeneration of the wound surface in the absence of metabolic disorder. It is quite likely that all the dermal zones under study, especially the dermis on the border with the hypoderm, are involved in the regeneration process of the affected area, whereas on the periphery of the damaged area, it is mainly the dermal zone located on the border of the reticular dermis and the hypoderm that is involved.

Incorporation of Methoxyphenamine into Hair in Early Stage after Intake.

In order to investigate the incorporation behavior of drugs into hair in early stage (within 24 h) after intake, time-course changes in drug distribution in black hair were carefully analyzed after a single oral administration of methoxyphenamine (MOP), a non-regulated analog of methamphetamine. Single-hair specimens collected by plucking with the roots intact at appropriate intervals post-intake were each divided into 1-mm segments from the proximal end, and MOP in each segment was determined by a validated liquid chromatography-tandem mass spectrometry procedure. At 10 min after intake, MOP was not detected in any of the segments. MOP became detectable 30 min after intake in the hair bulb (0-1-mm segment from the proximal end) and 1 h after intake in the upper dermis zone (1-2-mm to 4-5-mm segments). The amount of MOP in the hair bulb increased rapidly over 3 h after intake and reached a maximum concentration of ∼100-900 pg/1-mm single hair (11-95 ng/mg) around 3-10 h after intake, whereas that in the upper dermis zone increased at a more gradual pace over 24 h and reached a plateau at ∼30-100 pg/1-mm hair (3-11 ng/mg). These differences can be attributed to the different incorporation mechanisms of the drug. Results from this study can further elucidate the drug incorporation mechanism, which is crucial for accurately interpreting results in hair analyses. Our findings also suggest that hair drug analysis with special attention to the hair root can serve as a useful complementary approach to urine- and blood-based testing in the field of forensic toxicology.

Incorporation of zolpidem and methoxyphenamine into white hair strands after single administrations: Influence of hair pigmentation on drug incorporation

In order to investigate the influence of pigmentation on the incorporation of drugs into hair, time-course changes in drug distribution along non-pigmented (white) hairs as well as pigmented (black) hairs plucked from the same subject was observed following single administrations of two basic drugs with different properties, zolpidem and methoxyphenamine. These drugs in 1-mm sections of single hair specimens were each determined by a liquid chromatography–tandem mass spectrometric procedure. During the early stage (12–36 h) after intake, for black hairs, both drugs were detected over the entire area of hair root (4–5 mm in length), in which notable concentration of these drugs in the hair bulb (0–1-mm segment from the bottom of hair root, Region 1) and lower concentrations in the upper dermis zone (1–2-mm to 3–4-mm or to 4–5-mm segments, Region 2) were commonly observed. Meanwhile, for white hairs, high drug concentrations in Region 1 as detected in black hairs were not observed although only small amounts of these drugs were detected over Region 2. Subsequent time-course changes in the concentration of drugs in hair demonstrated that the drugs once incorporated into white hair via Region 2 decreased gradually over the period from 24 h to 35 days after intake, but those of black hairs remained almost unchanged. These findings revealed here suggest that hair pigments have two important roles in the distribution of drugs: (1) incorporation of drugs into hair via Region 1, and (2) retention of already incorporated drugs in the hair tissue. These findings would be useful for discussing individual drug-use history based on hair analysis in the forensic fields.

Aggravation of mild axillary hidradenitis suppurativa by microwave ablation: Results of a randomized intrapatient–controlled trial

_To the Editor:_ Hidradenitis suppurativa (HS) is a common chronic, recurrent, autoinflammatory skin disease of the hair follicle with limited treatment options. No definitive treatment exists for this debilitating entity. MiraDry (Miramar Labs Incorporated, Santa Clara, CA) is a microwave device targeting the eccrine and apocrine sweat glands as well as hair follicles through thermolysis in the dermal-hypodermal junction. We hypothesized that this noninvasive ablative technique could potentially improve the clinical symptoms of HS by reducing the number of hair follicles (primary action) and the destruction of the inflammatory cell infiltrate (secondary action) in HS lesions. We, therefore, evaluated the efficacy and safety of miraDry treatment for mild axillary HS in a randomized intrapatientecontrolled trial (ethical approval by the IRB of the Erasmus University Medical Center; MEC-2017-390). [...]

Incorporation of Zolpidem into Hair and Its Distribution after a Single Administration.

To obtain fundamental information on the drug incorporation into hair, time-course changes in drug distribution along single-strand hair were observed after a single oral administration of zolpidem (ZP), one of the most frequently used hypnotic agents. Quantitative sectional hair analyses of 1-mm segments were performed for each single-strand hair using a validated LC-MS/MS procedure. ZP was detected in all specimens plucked at 10 and 24 hours after a single dose, and the distribution ranged over the whole hair root (4-5 mm in length). A significantly high concentration of ZP was detected in the hair bulb region, whereas much lower concentrations were widely observed in the upper part of the hair root of those samples; this suggested that the incorporation of ZP occurred in two regions, mainly in the hair bulb and to a lesser extent in the upper dermis zone. The ZP-positive area formed lengths of up to 10-12 mm after a single administration, indicating that its incorporation from the hair bulb would continue for about 2 weeks. Time-course changes in the ZP concentration in the hair root additionally revealed that only a small portion of ZP that initially concentrated in the bulb was successively incorporated into the hair matrix and moved toward the keratinized region as hair grew. These findings should be taken into account upon discussing individual drug-use history based on hair analysis. The matrix-assisted laser desorption/ionization mass spectrometry imaging of ZP in the same kinds of hair specimens was also successfully achieved.

Time-course mass spectrometry imaging for depicting drug incorporation into hair.

In order to investigate the incorporation of drugs into hair, matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MS/MS) imaging was performed on the longitudinal sections of single scalp hair shafts sampled from volunteers after a single oral administration of methoxyphenamine (MOP), a noncontrolled analogue of methamphetamine. Hair specimens were collected by plucking out with the roots intact, and these specimens were prepped by an optimized procedure based on freeze-sectioning to detect the drug inside the hair shaft and hair root. Time-course changes in the imaging results, with confirmatory quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for each 1-mm segment of single hair strands, revealed a substantial concentration of the drug first onto the hair bulbs after ingestion, while only a small portion appeared to be incorporated into the hair matrix, forming a 2-3 mm distinctive drug band with tailing. Comparable amount of the drug also appeared to be incorporated into the keratinized hair shaft in the upper dermis zone, forming another distinct drug band of about 2 mm, which both moved toward the distal side, following the strand's growth rate. These findings provide forensically crucial information: there are two major drug incorporation sites, at least for MOP, which cause overlap of the recordings and deteriorates its chronological resolution down to about 11 days or perhaps longer.

Minimally invasive lateral retroperitoneal transpsoas interbody fusion for L4–5 spondylolisthesis: clinical outcomes

In this study the authors report on the clinical outcomes, safety, and efficacy of lateral retroperitoneal transpsoas minimally invasive surgery-lumbar interbody fusion (MIS-LIF) at the L4-5 disc space in patients with spondylolisthesis. This approach has become an increasingly popular means of fusion. Its most frequent complication is lumbar plexus injury. Reported complication rates at the L4-5 disc space vary widely in the literature, bringing into question the safety of MIS-LIF for the L4-5 region, especially in patients with spondylolisthesis. The authors retrospectively reviewed prospectively acquired multicenter databases of patients with Grade I and II L4-5 spondylolisthesis who had undergone elective MIS-LIF between 2008 and 2011. Clinical follow-up had been scheduled for 1, 3, 6, 12, and 24 months postoperatively. Outcome measures included estimated blood loss, operative time, length of hospital stay, integrity of construct, complications, fusion rates, visual analog scale (VAS), Oswestry Disability Index (ODI), and 36-Item Short Form Health Survey (SF-36). Eighty-four patients with L4-5 MIS-LIF were identified, 31 of whom met the study inclusion criteria: 26 adults with Grade I and 5 adults with Grade II L4-5 spondylolisthesis who had undergone elective MIS-LIF and subsequent posterior percutaneous pedicle screw fixation without surgical manipulation of the posterior elements (laminectomy, foraminotomy, facetectomy). The study cohort consisted of 9 males (29%) and 22 females (71%) with an average age of 61.5 years. The mean total blood loss was 94 ml (range 20-250 ml). The mean hospital stay and follow-up were 3.5 days and 18.2 months, respectively. The average score on the ODI improved from 50.4 preoperatively to 30.9 at the last follow-up (p < 0.0001). The SF-36 score improved from 38.1 preoperatively to 59.5 at the last follow-up (p < 0.0001). The VAS score improved from 69.9 preoperatively to 38.7 at the last follow-up (p < 0.0001). No motor weakness or permanent deficits were documented in any patient. Correction of deformity did not have any neurological complications. All patients had improvement in anterolisthesis. Residual postoperative listhesis across cases was noted in 4 patients (12.9%). Transient anterior thigh numbness (Sensory Dermal Zone III) was noted in 22.5% of patients. With its established surgical corridors through the retroperitoneum and psoas muscle, the MIS-LIF combined with posterior percutaneous pedicle screw fixation/reduction is a safe, reproducible, and effective technique for patients with symptomatic degenerative spondylolisthesis at the L4-5 vertebral segment.

Matrix Therapy with RGTA OTR4120 Improves Healing Time and Quality in Hairless Rats with Deep Second-Degree Burns

ReGeneraTing Agents (RGTAs) are biodegradable polymers engineered to mimic heparan-sulfate in the extracellular matrix of damaged tissue. RGTAs improve tissue healing in several animal models by stabilizing and protecting heparin-binding growth factors and matrix proteins. RGTA restores the normal matrix architecture and supports tissue regeneration. In this study, the authors evaluated the effects of RGTA on epidermal repair and dermal remodeling in a rat burn model. Deep second-degree burns were induced in 156 hairless rats, of which half (n = 78) received topical and intramuscular RGTA immediately after the burn followed by intramuscular RGTA weekly for 1 month. The controls (n = 78) received saline according to the same protocol. Rats were killed starting on each day of the first week and on days 14, 28, 60, 120, 240, and 365. The burns were evaluated by photography, histology, and immunohistochemistry. Coagulation necrosis involved the entire epidermis and superficial adnexa. Compared with the controls, speed of epidermal repair, as assessed between days 3 and 7 based on cell-layer number and anticytokeratin-14 staining, was faster in the RGTA group; and the zone of stasis, as assessed based on secondary vascular lesions in the dermis, was smaller. On day 7, reepithelialization was complete in both groups. On days 14 and 28, the remodeled dermal zone was smaller in the RGTA group. RGTA accelerated epidermal repair and protected the dermis from secondary effects of heat as quantified by zone-of-stasis size and extent of dermal remodeling.

Elastophagocytosis in extragenital lichen sclerosus

Elastophagocytosis, or elastic fiber phagocytosis by multinucleate macrophages, has been observed in different skin conditions that may or may not occur on sun-exposed skin. Although loss of elastic fibers has been well documented in the homogenized papillary dermal zone in lichen sclerosus (LS), elastophagocytosis, to the best of our knowledge, has never been observed. We encountered striking elastophagocytosis in a case of extragenital LS which prompted us to review all cases of LS diagnosed at the Skin Pathology Laboratory at Boston University over a 2-year period to assess for the presence of elastophagocytosis. In 7 of 35 patients diagnosed with LS (20%), we found prominent elastophagocytosis to be present either immediately below or at the junction of the homogenized collagen and the normal underlying reticular dermis. Interestingly, all the cases in which elastophagocytosis was observed were in extragenital locations. Elastophagocytosis was observed in 20% of LS cases, all of which were extragenital. We hypothesize that elastophagocytosis in LS, especially in extragenital sites, may not be an epiphenomenon but rather represents a contributing factor to elastic fiber loss in the hyalinized papillary dermal collagen that typifies this disease.

Dynamic interaction of fingertip skin and pin of tactile device

The present paper deals with investigations performed with the aim to study transmitting tactile information into the area of mechanoreceptors of the fingertip skin segment and to estimate the dynamic properties and behavior of the skin by performing numerical analysis. A computational finite element model consisting of four main layers of skin was used for transient analysis of contact dynamic interaction when loading the skin by a moving pin, as well as for modal analysis of skin and analysis of skin stress–strain state under harmonic loading (a plane strain case was studied). Material properties of the skin were assumed as linear elastic because of a very small excitation signal level. The efficiency of the regime of the skin dynamic loading in terms of the tactile signal level was defined on the basis of the strain level in the dermis zone where mechanoreceptors are placed. The possibilities of using vibratory control signal were analyzed.

Cutaneous Balloon Cell Dermatofibroma (Fibrous Histiocytoma)

Dermatofibroma (DF) or cutaneous fibrous histiocytoma is a common benign skin tumor that exhibits multiple, distinct histologic variants. Although clear cell DF has been described in the literature, balloon cell degeneration causing a clear cell DF phenotype has been not been reported to date. Herein, we describe the clinicopathologic findings of balloon cell DF arising on the heel of a 43-year-old man. Clinically, it presented as enlarging tan-white, ulcerated, firm 1.5 cm nodule, clinically suspected to be pyogenic granuloma. Excisional biopsy revealed a circumscribed fibrous tumor populated by mostly clear and spindle cells. A zonal arrangement separated the varied tumor cells where the most superficial, polypoid area showed large, clear polygonal balloon cells; the mid-dermal zone demonstrated a transition between balloon cells, epithelioid cells, and spindle cells; and the deep dermal zone had storiform arrangement of spindle cells, with the fascicles separated by coarse collagen bundles. A CD10+ > CD68+ > Factor XIIIa+ immunophenotype was identified with negative immunolabeling for S-100 protein, HMB-45, cytokeratin AE1/AE3, desmin, smooth muscle actin, lysozyme, and leukocyte common antigen (LCA). Ultrastructurally, the clear tumor cells were filled with multiple, empty, nonmembrane bound vacuoles of varying size. No recurrence has been described after complete excision and 7 months of follow up. DF with balloon cell change, likely secondary to persistent irritation, should be added to the differential diagnosis of cutaneous primary and metastatic neoplasms showing balloon cell degeneration such as balloon cell melanocytic nevi and renal cell carcinoma, respectively.

Defocused CO2 laser on equine skin: a histological examination

No studies have been published on effects of treatment with a defocused beam carbon dioxide (CO2) laser on equine skin histology. A better understanding of this will help to define how lasers should be used, in order to reduce potential side effects. To describe the acute effects of different doses of defocused CO2 laser, ranging from therapeutic to surgical levels, on equine skin. Defocused CO2 laser was administered to the skin in the hamstrings (91 J/cm2), fetlock (137 J/cm2) and loin (450 J/cm2) areas of 13 Standardbred horses. The acute effects on skin histology were examined 90 min after the end of therapy. Mild changes with focal spongiosis and subepidermal clefts were found after 91 J/cm2 irradiation and more severe changes with diffuse subepidermal clefts after the 137 J/cm2 dose. A homogeneous eosinophilic acellular zone of dermis and destruction of adnexal structures, and significant thinning of the epidermis was observed after the 450 J/cm2 dose. The present study indicates acute dose-dependent changes in equine skin histology after laser treatment Severe tissue damage was induced using a 450 J/cm2 dose. To reduce the potential side effects of defocused CO2 laser treatment, the laser parameters must be carefully evaluated. Caution should be taken if doses higher than 91 J/cm2 (16 W, 4 min, and 42 cm2) are used in irradiation of equine skin.

In vitro degradation of porcine skin epidermis by a fungal keratinase of Doratomyces microsporus

A keratinase, produced biotechnologically by Doratomyces microsporus, was used to treat porcine skin in vitro under different experimental conditions. The amount of soluble proteins, their electrophoretic profile and the histological appearance of the skin cuttings were followed. The amount of soluble protein released by the keratinase was maximal after 6 h of incubation in neutral or alkaline environments up to pH 9. With prolonged incubation, the amount of protein released due to the enzyme decreased on account of further hydrolysis of soluble proteins into smaller units. As shown by SDS-PAGE, the proteins of 45–70 kDa detected in controls were hydrolysed by the enzyme to fragments of 14 kDa or less after 3 h incubation in the optimal pH range. Histological examination of the skin cuttings suggested that the enzyme was active throughout the incubation period, since the effect on epidermis progressed with time. Stratum corneum was detached from the underlying layers of epidermis that were severely disintegrated and separated from the unaffected dermis at the epidermal–dermal zone. Keratinase also hydrolysed the outer epithelial sheath of hair roots provoking depilation. These data suggest the potential of this enzyme for application in ecologically-friendly leather processing.

Human skin mast cells: in vitro and in vivo studies.

This short review surveys our current knowledge on the development and heterogeneity of human mast cells, the distribution of mast cells within human skin and the properties of human skin mast cells both in vitro and in vivo. It also examines the effects of antihistamines in the wheal-and-flare response in the skin provoked by bradykinin. Mast cells derive from mononuclear precursor cells which undergo their final phase of their differentiation in the tissues. In normal skin, mast cells, which are primarily of the MC(TC) subtype, occur in the greatest density in the superficial dermal zone. Like all other mast cells, human skin mast cells bind IgE with high affinity to specific FcepsilonRI receptors, but unlike those from lung, tonsils, adenoids or intestine, they also express the C5a receptor (CD88) and activation sites for substance P, VIP, somatostatin, and compound 48/80. Both IgE-dependent stimulation by activating tyrosine kinases, and non-immunologic stimulation by activating G-proteins induce a characteristic compound exocytosis resulting in the liberation of the preformed mediators. Production of prostaglandin D2 and leukotriene C4, however, occurs only with IgE-dependent stimulation. In vivo, dermal microdialysis and scanning laser Doppler imaging have been used to assess the role of histamine in the wheal-and-flare response. These techniques were also used to show that low concentrations of intradermal bradykinin release negligible quantities of histamine. The results showed that although the resultant flare was inhibitable by antihistamines, low concentrations of bradykinin released negligible quantities of histamine. This suggests a potentially novel mechanism of action of antihistamines that requires further detailed investigation.

The effect of tissue expansion on the expression of collagen type I and type III mRNA in distinct areas of skin in the dog as an animal model.

To evaluate the transcriptional response of skin to tissue expansion in the dog, the expression of procollagen alpha 1(I) mRNA and procollagen alpha 1(III) mRNA were analyzed by in situ hybridization. This expression was evaluated in distinct skin areas (subepidermal zone, dermis, capsular zone) after 4-85 days of expansion. Within the first 4 days of expansion expression of procollagen alpha 1(I) and alpha 1(III) mRNA was not affected in the subepidermal and dermal zone. Only a slightly elevated level of type III procollagen mRNA was demonstrated in tissue surrounding the implanted silicone expander. After 7 days of expansion an enhanced level of procollagen alpha 1(III) mRNA was observed in the dermis and capsular zone. A slightly enhanced type I collagen mRNA level occurred in all zones of the dermis that was even stronger in the capsular zone after 9 days of expansion. Concurrently, the number of transcriptionally active cells was significantly higher. Return to the basal level of procollagen alpha 1(I) mRNA was attained after 40 days. At this time a significant expression of procollagenase mRNA was observed. Procollagen III mRNA expression reached its basal level on day 85.

Reduction Mammaplasty with a Sliding Nipple Technique

Ninety-four consecutive patients (19 who underwent mastopexy, and 75 who underwent reduction mammaplasty) were reviewed. They had all been operated on using a sliding manoeuvre for transfer of the nipple-areola complex on its underlying parenchyma, which has been in use for reduction mammaplasty in our unit since 1978. This makes it possible to slide the nipple-areola complex on the glandular tissue by making incisions in the de-epithelialised dermal zone on both sides of the areola, and leaving a dermal bridge above. The technique increases the mobility of the nipple-areola complex without jeopardising the blood supply, and is a combination of horizontal and superior pedicle techniques. The patients had been followed up for three to six months, except for five who had been followed up for five to six years. Minor early complications occurred in two patients. The sliding nipple technique is applicable to most types of mammary ptosis and hypertrophy, except those with a sclerotic and stiff parenchyma.

Vitamin A and β-Carotene Concentrations at Different Depths of the Epidermis: A Preliminary Study in the Cow Snout

Vitamin A (retinol) is an anti-keratinizing agent essential for normal epithelial differentiation. In order to examine the epidermal distribution of vitamin A and provitamin A (beta-carotene), we took advantage of the extraordinarily thick snout epidermis of the cow which can be cut horizontally into at least 6 layers, representing keratinocytes at different stages of maturation. Extracts of saponified samples were analyzed for retinol and beta-carotene by reversed phase high-performance liquid chromatography. The highest retinol concentration (0.8 micrograms/g protein; n = 3) was recorded closest to the dermis; progressively decreasing amounts of retinol were found in the upper parts of epidermis. Maximum values of beta-carotene (1.0 micrograms/g; n = 7) were found in the lower parts of epidermis; substantially lower levels were seen at the dermal transition zone and in the upper parts of epidermis. The results suggest that the endogenous concentration of vitamin A in snout epidermis is inversely related to the degree of cellular differentiation.

ICR系白内障ラットにみられる胸腺早期萎縮と皮膚炎の発生について

During the process of developing of the ICR-cataractous rat as an established strain, a substrain was found, which showed an early occurrence of thymus atrophy accompanied with the skin lesions. In order to make an elementary elucidation on the constitutional factors of these disorders, we observed changes in the weight and the organ/body weight ratio of thymus and histological findings of it as well as of the skin.An accelerated process of the thymus atrophy was sho wn at the early stage of two months age in both sexes, especially in the males, being more significant after the age of three months. In regard to the histological findings, a significant atrophy of the thymus parenchyma including its cortex, was observed, being consistent with those of the organ weight or the organ/body weight ratio. At five months of age, the thymus parenchyma was completely replaced by swollen lymph nodes in some cases.After two months of age, there appeared also the encrusted or erosive skin lesions occurring symmetrically in the cervical (including retro- or subauricular regions), the scapular and besides the dorsal regions (except the lumbar region). They could be, in part, ascribed to secondary scratching effects. However, we simultaneously observed, on the histological level, characteristic lesions such as a significant acanthosis of the epidermis especially around the hair follicles, as well as thickening of the keratohyalin zone and hyper-, para-keratosis, slight to moderate spongiosis, extension of the inflammatory infiltrate into the epidermis, inflammation of the dermal zone, hyperplasia of the sebaceous glands and perifolliculits, especially showing infiltration of mononuclear cells into the follicular region. These lesions may be regarded as a disease entity of “dennatitis” because they showed a marked similarity with the atopic or seborrheic dermatitis seen in humans. Therefore, the ICR/d-strain rat may be useful as a good disease model for elucidating the occurrence mechanisms of such dermatItis.