Combined microneedling with topical application of platelet-rich plasma versus microneedling alone in the treatment of stria distensae: clinicopathological analysis.

BACKGROUND: Striae distensae (SD) are common skin conditions. OBJECTIVES: This study was done to test the hypothesis that 'the use of microneedling (MN) before platelet-rich plasma (PRP) application will allow for deeper penetration and therefore, augment its efficacy in the treatment of SD.' PATIENTS AND METHODS: Forty patients with SD were divided into (i) Group I, the patients were treated with MN only, and (ii) Group II, the patients were treated with combined MN-PRP. The clinical improvement was evaluated by two dermatologists. Skin biopsies were obtained before and after therapy to examine immunohistological changes. RESULTS: As compared to the use of MN alone, therapy with combined MN-PRP was associated with: (i) a marked to the excellent improvement of the skin lesions of SD, (ii) a more significant deposition of collagen and elastic fibers, (iii) increased proliferative activity in the epidermis, and (iv) a decreased caspase-3 protein expression values in the epidermis. CONCLUSIONS: This study proved that the combined MN-PRP is more effective than MN alone for the treatment of the lesions of SD. The underlying molecular mechanisms are open for future studies.

Primary Basidiobolomycosis of the Cecum in Immunocompetent Patients: Two Case Reports.

Colonic basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum. Primary cecal basidiobolomycosis is an exceptionally rare condition. The study describes two cases of primary basidiobolomycosis of the cecum in immunocompetent male and female patients (one each). The patients presented with fever, abdominal pain, weight loss, eosinophilia, and high erythrocyte sedimentation rates. Computed tomography revealed wall thickening and mass lesions involving the cecum, suggesting malignancy. Right hemicolectomies were performed to relieve the intestinal obstruction. On microscopy, there were destructive, transmural eosinophil-rich pyogranulomatous reactions with thin-walled, pauci-septated fungal elements surrounded by Splendore-Hoeppli bodies. The patients received antifungal drugs, with no evidence of dissemination or recurrence on follow-up. Primary cecal basidiobolomycosis in immunocompetent hosts is a rare occurrence. It oftentimes clinically masquerades malignant neoplasms and therefore its identification mandates its inclusion in the differential diagnosis of a colonic mass, equally both on the part of the clinicians and pathologists.

A Unique Coexistence of Rectal Adenocarcinoma and Gastric Antral Gastrointestinal Stromal Tumor: A Case Report and Minireview.

Several studies have reported the coexistence of gastric gastrointestinal stromal tumors (GISTs) with many primary carcinomas such as gastric and renal cell carcinomas. However, to date reports about the coexistence of gastric GISTs and colorectal adenocarcinoma are limited. Herein we report a unique case of gastric GIST coexisting synchronously with rectal adenocarcinoma in a 36-year-old male patient who presented with weight loss, vomiting, and bleeding per rectum. Computed tomography (CT) revealed circumferential rectal mass coexistent with an irregular gastric soft tissue mass. The diagnosis of rectal adenocarcinoma and gastric GIST was established by immunohistological evaluation of the colonoscopic (rectum) and CT-guided (stomach) biopsies. The patient received concomitant chemoradiotherapy for the rectal adenocarcinoma and neoadjuvant imatinib for the gastric GIST. This was followed by low anterior resection with total mesorectal excision and wedge resection of the gastric mass. Follow-up of the patient for 1.5 years revealed no evidence of disease recurrence. We also present a minireview of the literature that provides insights into this subject as a separate section.

Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis- and autophagy-associated molecules.

In clinical medicine, indomethacin (IND, a non-steroidal anti-inflammatory drug) is used variously in the treatment of severe osteoarthritis, rheumatoid arthritis, gouty arthritis or ankylosing spondylitis. A common complication found alongside the therapeutic characteristics is gastric mucosal damage. This complication is mediated through apoptosis and autophagy of the gastrointestinal mucosal epithelium. Apoptosis and autophagy are critical homeostatic pathways catalysed by caspases downstream of the gastrointestinal mucosal epithelial injury. Both act through molecular signalling pathways characterized by the initiation, mediation, execution and regulation of the cell regulatory cycle. In this study we hypothesized that dysregulated apoptosis and autophagy are associated with IND-induced gastric damage. We examined the spectra of in vivo experimental gastric ulcers in male Sprague-Dawley rats through gastric gavage of IND. Following an 18-hour fast, IND was administered to experimental rats. They were sacrificed at 3-, 6- and 12-hour intervals. Parietal cells (H+ , K+ -ATPase ß-subunit assay) and apoptosis (TUNEL assay) were determined. The expression of apoptosis-signalling caspase (caspases 3, 8, 9 and 12), DNA damage (anti-phospho-histone H2A.X) and autophagy (MAP-LC3, LAMP-1 and cathepsin B)-related molecules in gastric mucosal cells was examined. The administration of IND was associated with gastric mucosal erosions and ulcerations mainly involving the gastric parietal cells (PCs) of the isthmic and upper neck regions and a time-dependent gradual increase in the number of apoptotic PCs with the induction of both apoptotic (upregulation of caspases 3 and 8) cell death and autophagic (MAP-LC3-II, LAMP-1 and cathepsin B) cell death. Autophagy induced by fasting and IND 3 hours initially prompted the degradation of caspase 8. After 6 and 12 hours, damping down of autophagic activity occurred, resulting in the upregulation of active caspase 8 and its nuclear translocation. In conclusion we report that IND can induce time-dependent apoptotic and autophagic cell death of PCs. Our study provides the first indication of the interactions between these two homeostatic pathways in this context.

Ultra-structural study of the indomethacin-induced apoptosis and autophagy in rat gastric parietal cells.

BACKGROUND AND AIM OF THE WORK: Indomethacin (IND), a non-steroidal anti-inflammatory drug, can induce gastric mucosal ulcerations. To date, the ultra-structural changes in the parietal cells (PCs) of the gastric mucosa following the intake of IND are mostly unknown. We carried out the current investigation to get insights into this issue. MATERIALS AND METHODS: We established an animal model consisting of 35 adult male Sprague Dawley rats. The animals were divided into three groups, including; control (normal feeding), fasting, and indomethacin-treated groups. After treatment of 18-h fasting rats with IND, they were sacrificed at 3, 6, and 12-h intervals. The morphological features, including the apoptotic, and autophagic changes in the gastric mucosa PCs were examined using transmission electron microscopy. RESULTS: In normal feeding animals (control group), the gastric PCs were present in various stages of activity. Fasting was associated with the predominance of the inactive parietal cells with features of up-regulated autophagy. In the IND -treated animals (at 3-h interval), PCs showed prominent autophagic changes, and subtle apoptotic cell death. In the IND -treated animals (at 6-12-h interval), PCs showed prominent apoptotic changes, and subtle autophagic features. CONCLUSIONS: Our study indicates that IND treatment could induce gastropathy through time-dependent alterations in the autophagic and apoptotic machinery of PCs. Further studies are needed to examine the underlying molecular mechanisms.

Dermal morphological changes following salicylic acid peeling and microdermabrasion.

BACKGROUND: Microdermabrasion and chemical peeling are popular, inexpensive, and safe methods for treatment of some skin disorders and to rejuvenate skin. OBJECTIVES: To study the alterations of the dermal connective tissue following salicylic acid peeling and microdermabrasion. METHODS: Twenty patients were participated in our study. All participants underwent facial salicylic acid 30% peel or microdermabrasion (10 cases in each group) weekly for 6 weeks. Punch biopsies were obtained from the clinically normal skin of the right postauricular region 1 week before treatment (control group). Other punch skin biopsies were obtained 1 week after the end of the treatments from the left postauricular area. This region was treated in a similar way to the adjacent lesional skin (treated group). We used routine histological techniques (H&E stain), special stains (Masson trichrome and orcein stains), and image analyzer to study the alterations of the dermal connective tissues. RESULTS: Our study demonstrates variations in the morphological changes between the control and the treated groups, and between chemical peels and microdermabrasion. Both salicylic acid 30% and microdermabrasion were associated with thickened epidermal layer, shallow dermal papillae, dense collagen, and elastic fibers. There was a significant increase among those treated sites vs control regarding epidermal thickness and collagen thickness. Also, there was a highly statistically significant increase among those treated with salicylic acid vs microdermabrasion regarding the epidermal, collagen, and elastin thickness. CONCLUSIONS: Both methods stimulate the repair process. The mechanisms underlying these variations are open for further investigations.

Steroid therapy is associated with decreased numbers of dendritic cells and fibroblasts, and increased numbers of satellite cells, in the dystrophic skeletal muscle.

BACKGROUND: The possible therapeutic benefits of using steroids to enhance muscle strength and slow disease progression in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) has been examined previously. In this investigation, it was hypothesised that steroid therapy is associated with morphological changes in the dystrophic muscle. OBJECTIVES AND METHODS: To test this hypothesis, two muscle biopsies were obtained (one biopsy before treatment, and the second 6 months following prednisone therapy) from 24 patients with dystrophies (18 DMD, 6 BMD). The participants were categorised into: control (6 specimens, normal muscle), untreated and treated groups. The muscle was evaluated for ultrastructural changes using transmission electron microscopy (TEM). RESULTS: In the untreated group, the muscle fibres were degenerated and of variable sizes. The myofibrils were thin with either complete loss of bands and/or abnormal banding patterns. The Z-lines were irregularly spaced and loosely registered. The mitochondria of the myofibrils were small, few, spherical and irregularly distributed. Numerous dendritic cells (DCs) with euchromatic nuclei, and multiple and long dendrites, were seen among the myofibrils. The collagen fibres among the muscle fibres (endomysium) were numerous and large. The satellite cells had euchromatic nuclei with clumps of heterochromatin. In the treated group, the muscle fibres had a relatively uniform size with occasional fibres showing partial degeneration. The myofibrils had a relatively similar diameter comparable to that of normal muscle .The degenerated areas were small in size with occasional foci showing loss of banding pattern, and abnormal short bands with thick and hazy Z-lines. The mitochondria of the myofibrils were numerous, spherical, small in size and regularly arranged between the myofibrils. Few DCs, with heterochromatic nuclei, and few and short dendrites appeared between the myofibrils. The collagen fibres between the muscle fibres (endomysium) were numerous and large. As compared with the treated group, there was a statistically significant increase (p<0.05) in the numbers of DCs (0.7+/-0.2 vs 1.6+/-0.3) and fibroblasts (1.9+/-0.2 vs 2.9 +/-0.3) in the untreated group. Alternatively, there was a statistically significant decrease (p<0.05) in the numbers of satellite cells (1.2+/-0.2 vs 0.6+/-0.1). CONCLUSION: The ability of steroids to induce ultrastructural features of improvement supports the notion that they have beneficial therapeutic role. The clinical ramifications of these observations mandate further studies.

Do viscid secretions have a role in nasal polyp formation?

OBJECTIVES: We compared histologic findings on light microscopy of viscid secretions found in association with nasal polyps with those found in patients with chronic sinusitis without polyposis (CSWP). The differences might further understanding of nasal polyp pathogenesis. METHODS: In a prospective controlled study, viscid secretions found in association with nasal polyps were collected at endoscopic sinus surgery. Retained secretions in patients with CSWP acted as a control group. Both were fixed in 10% formalin, processed, and examined with a light microscope. RESULTS: Viscid secretions were encountered among nasal polyps in 25 of 132 patients (18.9%). Polyps containing multiloculated cysts filled with viscid secretions were found in 2 of them. Histologic examination of viscid secretions showed variable histologic pictures, ranging from a homogeneous material infiltrated with inflammatory cells, newly formed blood vessels, and bundles of collagen fibers to a well-developed connective tissue core covered with a respiratory epithelium in some areas. Histologic examination of retained secretions in patients with CSWP revealed amorphous material infiltrated with inflammatory cells with no further maturation or epithelial coverage. CONCLUSIONS: Viscid secretions, originating from ruptured mucosal cysts, might represent the initial step in nasal polyp pathogenesis. The variable histologic pictures detected possibly reflect different stages in nasal polyp formation from these secretions. Factors postulated in nasal polyp etiopathogenesis might trigger maturation and changes in the morphological structure of these secretions.

Immune cell profile in invasive cholesteatomas: preliminary findings.

BACKGROUND: Cholesteatoma consists of keratinizing squamous epithelium, granulation tissue and keratin plugs. The pathogenesis of cholesteatoma may be related to alterations in the stromal immune cell infiltrate. OBJECTIVE: To examine the immunophenotypic characteristics of the immune cell infiltrate in invasive cholesteatomas. MATERIALS AND METHODS: This study included 12 patients with invasive cholesteatomas causing wide bone erosion of the mastoid, middle ear structures, and the bony plates of middle ear cleft. Diagnosis of invasiveness was based on the clinical, radiological and intraoperative findings. Canal wall-down surgical approach was done in all cases to control the disease process. We used the cholesteatomatous tissue specimens to perform immunohistochemical stains for B cells (CD20), T cells (CD3), histiocytes (CD68) and Langerhans' cells (CD1a). Mouse monoclonal antibodies and immunoperoxidase staining methods were used. The results of immunohistology were scored as mean values of positively stained immune cells. The data were compared with findings in 10 specimens of external ear skin (control group). RESULTS: Immunohistochemistry showed highly significant (p<0.00) counts of immune cells in invasive cholesteatomas (CD3: 4.7+/-0.4, CD68:4.6+/-0.5, CD20: 0.8+/-0.1 and CD1a: 0.8 +/-0.1) compared to those in external canal skin (control group: CD3:0.8+/-0.3, CD68: 1.0+/-0.4, CD20: 0.2+/-0.1 and CD1a: 0.1+/-0.1). In cholesteatomas, the predominant of CD3(+) T lymphocytes and CD68(+) cells (histiocytes). Rare CD20(+) cells and CD1a(+) cells (Langerhans' cells) were also observed. CONCLUSIONS: This preliminary study describes the profile of the immune cell infiltrate in invasive cholesteatomas. The numeric dominance of CD3(+) cells and CD68(+) cells suggests that cell-mediated immunity has important role in the development of cholesteatoma and in its autodestructive properties. Further studies are recommended to categorize the T cell subsets in different stages of cholesteatomas.

Melatonin and roentgen irradiation-induced acute radiation enteritis in Albino rats: an animal model.

BACKGROUND: Roentgen irradiation can affect normal cells, especially the rapidly growing ones such as the mucosal epithelial cells of the small intestine. The small intestine is the most radiosensitive gastrointestinal organ and patients receiving radiotherapy directed to the abdomen or pelvis may develop radiation enteritis. Although roentgen rays are widely used for both imaging and therapeutic purposes, our knowledge about the morphological changes associated with radiation enteritis is lacking. HYPOTHESIS: This study tries to tests the hypothesis that "the intake of melatonin can minimize the morphological features of cell damage associated with radiation enteritis". OBJECTIVES AND METHODS: We performed this investigation to test our hypothesis and to examine the possible radioprotective effects of melatonin in acute radiation enteritis. To achieve these goals, an animal model consisting of 60 Albino rats was established. The animals were divided into five groups: Group 1, non-irradiated; Group 2, X-ray irradiated (X-ray irradiation, 8 Grays); Group 3, X-ray irradiated-pretreated with solvent (ethanol and phosphate buffered saline); Group 4, non-irradiated-group treated with melatonin, and Group 5, X-ray irradiated-pretreated with melatonin. The small intestines were evaluated for gross (macroscopic), histological, morphometric (light microscopy), and ultrastructural changes (transmission electron microscopy). RESULTS: We found morphological variations among the non-irradiated-group, X-ray irradiated-group and X-ray irradiated-intestines of the animals pretreated with melatonin. The development of acute radiation enteritis in X-ray irradiated-group (Groups 2 and 3) was associated with symptoms of enteritis (diarrhea and abdominal distention) and histological features of mucosal injury (mucosal ulceration, necrosis of the epithelial cells). There was a significant reduction of the morphometric parameters (villous count, villous height, crypt height and villous/crypt height ratio). Moreover, the ultrastructural features of cell damage were evident including: apoptosis, lack of parallel arrangement of the microvilli, loss of the covering glycocalyx, desquamation of the microvilli, vacuolation of the apical parts of the cells, dilatation of the rough endoplasmic reticulum, and damage of the mitochondrial cristae. In the non-irradiated-group and in X-ray irradiated-intestines of the animals pretreated with melatonin (Group 5), these changes were absent and the intestinal mucosal structure was preserved. CONCLUSION: Administration of melatonin prior to irradiation can protect the intestine against X-rays destructive effects, i.e. radiation enteritis. The clinical applications of these observations await further studies.

The postoperative histologic changes in the nasal mucosa following treatment with amoxycilline or rifampicin: preliminary findings.

This study examines the postoperative histologic changes in the nasal mucosa following treatment with amoxycilline or rifampicin. Three groups of nasal mucosal biopsies were obtained from 20 patients having undergone nasal surgery (partial middle turbinectomy). The first group was obtained immediately before surgery (control group). The second and third groups were taken postoperatively (after the first and 6 weeks of amoxycilline or rifampicin therapy, 10 patients each). The histologic changes in the nasal mucosa and the density of seromucinous glands were examined using histochemical methods and image analyzer. Amoxycilline treatment was associated with squamous metaplasia and a statistically significant reduction in the percent area of the seromucinous glands compared to the control group (p < 0.05). Rifampicin therapy was associated with minimal reduction in the density of the seromucinous glands and absence of metaplastic changes. In nasal surgeries, rifampicin but not amoxycilline had a beneficial effect on postoperative nasal mucosa status.

Melatonin and roentgen irradiation of the testis.

Melatonin is a free-radical scavenger and antioxidant. Roentgen irradiation of testis (animal model formed of albino rats) was associated with destruction and depletion of the germinal epithelial cells. In roentgen-irradiated, melatonin-pretreated animals, these changes were markedly ameliorated. Thus administration of melatonin before irradiation can protect testis from some of the destructive effects of roentgen irradiation.

Morphological evaluation of the radioprotective effects of melatonin against X-ray-induced early and acute testis damage in Albino rats: an animal model.

Irradiation has profound effects on the reproductive function. Our knowledge about radioprotective effects of melatonin against X-ray-induced testis damage is rudimentary. In this investigation, we hypothesized that melatonin can minimize germ-cell depletion and morphological features of cell damage in testis following X-ray irradiation (XRI). To examine these effects, and to test our hypothesis, an animal model comprised of 60 Albino rats was established. The animals were divided into five groups: Group 1, non-irradiated; Group 2, X-ray irradiated (XRI, 8 Grays); Group 3, XRI pretreated with solvent (ethanol and phosphate-buffered saline); Group 4, non-irradiated group treated with melatonin and Group 5, XRI pretreated with melatonin. The testes were evaluated for both histological (light microscopy) and ultrastructural changes (transmission electron microscopy). Histologically, there were marked depletions (66%) of the germinal epithelial cells, in XRI group (Groups 2 and 3), whereas these changes were almost absent in XRI testis of animals pretreated with melatonin (Group 5). The number of spermatogenic cells in XRI testis of animals pretreated with melatonin (Group 5) was comparable (95%) to that of non-irradiated group (Groups 1 and 4) but significantly (P < 0.05) higher than those in XRI testis (34%, Groups 2 and 3). Ultrastructurally, XRI testis (Groups 2 and 3) showed features of apoptosis (condensation of the nuclei, vacuolization of the cytoplasm, increased cytoplasmic density and apoptotic bodies). These features were absent in XRI testis of animals pretreated with melatonin (Group 5). Also, this Group showed features of an increased metabolic activity (large acrosomal vesicle, prominent Golgi, increased mitotic activity, increased complement of cytoplasmic organelles and appearance of nucleoli-like bodies). There was a minimal depletion of the Sertoli and Leydig cells following XRI. Also, morphological features of apoptosis were infrequent in these cells. Administration of melatonin (MEL) prior to irradiation can protect testis against its destructive effects. The protective effects include amelioration of germ-cell depletion and apoptotic changes. The clinical ramifications of these observations mandate further studies.

The effects of glucocorticoid therapy on the inflammatory and dendritic cells in muscular dystrophies.

Various clinical trials have documented the therapeutic benefit of glucocorticoids (GCs) in enhancing muscle strength and slowing disease progression of Duchenne and Becker muscular dystrophies (DMD/BMD). We hypothesized that GCs may have relevance to the differential anti-inflammatory effect on mononuclear inflammatory cells (MICs) and Dendritic cells (DCs) infiltrating the dystrophic muscles. In this prospective study, two muscle biopsies were obtained (before and after 6-month prednisone therapy) from 30 patients with dystrophies (DMD = 18; BMD = 6; and limb girdle muscular dystrophies (LGMD) = 6). MICs and DCs infiltrating the muscles were examined using mouse monoclonal antibodies and immunoperoxidase staining methods. Muscle strength was evaluated monthly by manual testing, motor ability and timed tests. Prednisone therapy was associated with: (i) functional improvement of overall motor disability, in upper limbs of DMD (P < 0.001) and BMD (P < 0.01) and lower limbs of DMD (P < 0.001) and BMD (P < 0.05); (ii) histological improvement such as fibre size variation (DMD, P < 0.01; BMD, P < 0.05), internalization of nuclei (DMD, P < 0.05), degeneration and necrosis (DMD and BMD, P < 0.01), regeneration (DMD, P < 0.001; BMD, P < 0.01) and endomysial connective tissue proliferation (DMD, P < 0.01; BMD, P < 0.05) and (iii) reduction of total MICs (P < 0.01) and DCs (P < 0.01). There was a positive correlation between the degree of improvement in overall motor disability and reduction of DCs numbers (In upper limbs; r = 0.638, P < 0.01 for DMD and r = 0.725, P < 0.01 for BMD, in Lower limbs; r = 0.547, P < 0.05 for DMD and r = 0.576, P < 0.05 for BMD). Such improvements and changes of MICs/DCs were absent in LGMD. In DMD/BMD, prednisone therapeutic effect was associated with reduced MICs and DCs numbers. Whether this therapeutic effect reflects targeting of the deleterious immune response produced by these cells mandates further investigations.

Quantitative comparison of infected Schistosomiasis mansoni and Haematobium: animal model analysis of the granuloma cell population.

To evaluate the hypothesis that the granuloma cell population in S. haematobium is different from that of S. mansoni infections, a hamaster animal model was established. Infection of hamesters was induced by abdominal skin exposure of male golden hamsters with 300 cercariae. S. haematobium granuloma cell population in the small intestine, urinary bladder, liver and spleen and those of S. mansoni granuloma in the small intestine and liver of infected hamsters were histologically examined between 6 and 12 weeks post-exposure. In both species, the granuloma cell population was fomed of lymphocytes (47%), histiocytes (28%), eosinophils (16%) and polymorphs (8%). As compared to granuloma cell population in S. haematobium; S. mansoni granulomas had: (a) higher population of eosinophils (28% vs. 11%), (b) lower population of polymorphs (4% vs. 10%) and histiocytes (22% vs. 31%) and (c) similar population of lymphocytes (46% vs.47%). The mean diameter of liver granuloma was higher in S. mansoni (175.8 +/- 12.34) than for S. haematobium (125.4 +/- 16.12). As compared to S. haematobium, the numbers of isolated male, female and total worms were significantly higher in S. mansoni (24.5 +/- 2.7 vs. 7.3 +/- 2.3; 6.3 +/- 0.8 vs. 2.2 +/- 0.5; 80 +/- 2.2 vs. 56.3 +/- 3.8, p < .0.05). The heterogeneity of cell population in granuloma suggests the involvement of different immune mechanisms in their development. The cells achieving numerical dominance in the granulomas were in the following order: lymphoyctes > monocytes > eosinophils > polymorphs. The differrence in the granuloma cell population between S. haematobium and S. mansoni may reflect different tissue reactions to the deposited ova.

Ultrastructural evaluation of the radioprotective effects of melatonin against X-ray-induced skin damage in Albino rats.

Our knowledge about the radioprotective effects of melatonin against X-ray-induced skin damage is still lacking. To examine these effects, an animal model of 60 Albino rats was used. The animals were divided into five groups: Group 1, nonirradiated; Group 2, X-ray irradiated (XRI, 8 Gy); Group 3, XRI pretreated with solvent (ethanol and phosphate-buffered saline); Group 4, nonirradiated group treated with melatonin; and Group 5, XRI pretreated with melatonin. The skin was evaluated for ultrastructural changes using transmission electron microscopy (TEM). When compared to the nonirradiated skin (Groups 1 and 4), XRI skin (Groups 2 and 3) showed features of both cell injury and increased metabolic activity. The former included changes such as condensation of the nuclei, vacuolization of the cytoplasm, dilatation of the rough endoplasmic reticulum, swelling of the mitochondria with cristolysis, destruction of the ribosomes and intermediate filaments, fragmentation of the keratohyaline granules and loss of the irregularity of the basal cell borders. The central cells of the sebaceous gland alveoli had larger irregular nuclei and few lipid droplets in their cytoplasm. The hair follicle cells had heterochromatic nuclei and less electron dense cytoplasm containing few complements of the organelles. The features of increased metabolic activity included increased euchromatin, irregularity of the nuclear membrane and increased branching of the melanocytes. Also, an increased number of the Birbeck granules were seen in the Langerhans cells. When compared to the irradiated skin (Groups 2 and 3), these changes were mild or absent in the skin of XRI animals pretreated with melatonin (Group 5). The ability of melatonin to minimize the injurious effects of XRI suggests a radioprotective role. The clinical ramifications of these observations warrant further studies.