Clinical and pathological considerations in lumbar herniated disc associated with inflammatory lesions.

Lumbar herniated disc is the most frequent cause for lumbar pain. It is caused by degenerative, macroscopic and microscopic changes of the intervertebral discs. It is a chronic disease, with periods of exacerbation and remission under drug and physiotherapeutic treatment. When the disc lesions are large, with intense symptoms, reduced or impossible movements, with pain radiating to the sciatic nerve trajectory, a surgical treatment is required, to remove the herniated nucleus pulposus and decompress the nerve roots. Patients who present high inflammatory signs, high inflammatory serous markers, may have a longer postoperative recovery period, while the motor recovery may be late and incomplete. We analyzed a group of 24 patients with lumbar herniated disc that required discectomy, with clear inflammatory signs, together with histopathological and immunohistochemical changes present in the herniated disc.

Mutations in 3ß-hydroxysteroid-δ8, δ7-isomerase paradoxically benefit epidermal permeability barrier homeostasis in mice.

Inherited or acquired blockade of distal steps in the cholesterol synthetic pathway results in ichthyosis, due to reduced cholesterol production and/or the accumulation of toxic metabolic precursors, while inhibition of epidermal cholesterol synthesis compromises epidermal permeability barrier homeostasis. We showed here that 3ß-hydroxysteroid-δ8, δ7-isomerase-deficient mice (TD), an analog for CHILD syndrome in humans, exhibited not only lower basal transepidermal water loss rates, but also accelerated permeability barrier recovery despite the lower expression levels of mRNA for epidermal differentiation marker-related proteins and lipid synthetic enzymes. Moreover, TD mice displayed low skin surface pH, paralleled by increased expression levels of mRNA for sodium/hydrogen exchanger 1 (NHE1) and increased antimicrobial peptide expression, compared with wild-type (WT) mice, which may compensate for the decreased differentiation and lipid synthesis. Additionally, in comparison with WT controls, TD mice showed a significant reduction in ear thickness following challenges with either phorbol ester or oxazolone. However, TD mice exhibited growth retardation. Together, these results demonstrate that 3ß-hydroxysteroid-δ8, δ7-isomerase deficiency does not compromise epidermal permeability barrier in mice, suggesting that alterations in epidermal function depend on which step of the cholesterol synthetic pathway is interrupted. But whether these findings in mice could be mirrored in humans remains to be determined.

Inducible nitric oxide synthase is required for epidermal permeability barrier homeostasis in mice.

Nitric oxide (NO) regulates a variety of epidermal functions, including epidermal proliferation, differentiation and cutaneous wound healing. However, whether nitric oxide (NO) and its synthetic enzymes regulate epidermal permeability barrier homeostasis is not clear. In the present study, we employed inducible nitric oxide synthase (iNOS) KO mice to explore the role of iNOS in epidermal permeability barrier homeostasis. Our results showed that iNOS mice displayed a comparable levels of basal transepidermal water loss rates, stratum corneum hydration and skin surface pH to their wild-type mice, but epidermal permeability barrier recovery was significantly delayed both 2 and 4 hours after acute barrier disruption by tape stripping. In parallel, expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes were lower in iNOS KO mice versus wild-type controls. Topical applications of two structurally unrelated NO donors to iNOS KO mice improved permeability barrier recovery kinetics and upregulated expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes. Together, these results indicate that iNOS and its product regulate epidermal permeability barrier homeostasis in mice.

Diabetic foot - epidemiological and histopathological aspects.

Our study included a total of 259 patients with diabetes, who were admitted to the Department of Plastic Surgery and Reconstructive Microsurgery of the Emergency County Hospital of Pitesti, Romania, in 2016, with the diagnosis of "diabetic foot". Of the 259 patients, 55 (21.23%) were diagnosed with type 1 diabetes, and the remaining 204 (78.77%) were diagnosed with type 2 diabetes; the ratio of type 1∕type 2 diabetes was 1∕3.7. The injuries presented by the patients were osteitis (27.81%), moist gangrene (21.62%), abscesses (18.92%), cellulitis (11.19%), various forms of fasciitis (8.88%), perforating strand (6.18%), and dry gangrene (5.4%). The disease was most commonly diagnosed in males in the rural environment. Most of the patients were in the age group of 61-70 years old. All patients were surgically treated, but 142 (54.82%) patients needed amputations of foot segments (fingers, metatarsal or tarsal bones). The histopathological and immunohistochemical study on excised fragments revealed the existence of a chronic inflammatory process formed mainly from macrophages, mast cells and CD4+ T-lymphocytes.

Therapeutic Benefits of Natural Ingredients for Atopic Dermatitis.

Although a variety of regimens are available for the treatment of atopic dermatitis (AD), severe adverse reactions and unpopular costs often limit their usage. In contrast, certain inexpensive, naturally-occurring ingredients are proven effective for AD with fewer side effects. The beneficial effects of these ingredients can be attributed to inhibition of cytokine and chemokine expression, IgE production, inflammatory cell infiltration, histamine release, and/or the enhancement of epidermal permeability barrier function. Since herbal medicines are widely available, inexpensive and generally safe, they could be valuable alternatives for the treatment of AD, particularly for those patients who are not suitable for the utilization of immune modulators. In this review, we summarize the therapeutic benefits of natural ingredients for the treatment of AD and the mechanisms of their actions.

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines.

Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C-reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis and reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice leads not only to a rapid increase in cutaneous cytokine mRNA expression but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increase in otherwise normal, aged mice (>12 months). Third, expression of tumor necrosis factor-α and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with a significant elevation in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting that T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders.

Heavy Cigarette Smokers in a Chinese Population Display a Compromised Permeability Barrier.

Cigarette smoking is associated with various cutaneous disorders with defective permeability. Yet, whether cigarette smoking influences epidermal permeability barrier function is largely unknown. Here, we measured skin biophysical properties, including permeability barrier homeostasis, stratum corneum (SC) integrity, SC hydration, skin surface pH, and skin melanin/erythema index, in cigarette smokers. A total of 99 male volunteers were enrolled in this study. Smokers were categorized as light-to-moderate (<20 cigarettes/day) or heavy smokers (≥20 cigarettes/day). An MPA5 was used to measure SC hydration and skin melanin/erythema index on the dorsal hand, forehead, and cheek. Basal transepidermal water loss (TEWL) and barrier recovery rates were assessed on the forearm. A Skin-pH-Meter pH900 was used to measure skin surface pH. Our results showed that heavy cigarette smokers exhibited delayed barrier recovery after acute abrogation (1.02% ± 13.06 versus 16.48% ± 6.07), and barrier recovery rates correlated negatively with the number of daily cigarettes consumption (p = 0.0087). Changes in biophysical parameters in cigarette smokers varied with body sites. In conclusion, heavy cigarette smokers display compromised permeability barrier homeostasis, which could contribute, in part, to the increased prevalence of certain cutaneous disorders characterized by defective permeability. Thus, improving epidermal permeability barrier should be considered for heavy cigarette smokers.

Commonly Employed African Neonatal Skin Care Products Compromise Epidermal Function in Mice.

BACKGROUND: Neonatal mortality is much higher in the developing world than in developed countries. Infections are a major cause of neonatal death, particularly in preterm infants, in whom defective epidermal permeability barrier function facilitates transcutaneous pathogen invasion. The objective was to determine whether neonatal skin care products commonly used in Africa benefit or compromise epidermal functions in murine skin. METHODS: After twice-daily treatment of 6- to 8-week-old hairless mice with each skin care product for 3 days, epidermal permeability barrier function, skin surface pH, stratum corneum hydration, and barrier recovery were measured using a multiprobe adapter system physiology monitor. For products showing some benefits in these initial tests, the epidermal permeability barrier homeostasis was assessed 1 and 5 hours after a single application to acutely disrupted skin. RESULTS: All of the skin care products compromised basal permeability barrier function and barrier repair kinetics. Moreover, after 3 days of treatment, most of the products also reduced stratum corneum hydration while elevating skin surface pH to abnormal levels. CONCLUSION: Some neonatal skin care products that are widely used in Africa perturb important epidermal functions, including permeability barrier homeostasis in mice. Should these products have similar effects on newborn human skin, they could cause a defective epidermal permeability barrier, which can increase body fluid loss, impair thermoregulation, and contribute to the high rates of neonatal morbidity and mortality seen in Africa. Accordingly, alternative products that enhance permeability barrier function should be identified, particularly for use in preterm infants.

The Protective Role of Thiourea on Leuciscus cephalus Exposed to Sublethal Doses of Pendigan 330EC (Pendimethalin) Herbicide.

The aim of the study was to investigate the protective role of thiourea on the physiological, hematological, biochemical and histopathological parameters of Leuciscus cephalus exposed to sublethal concentration of Pendigan 330 EC herbicide. The animals were divided in four experimental groups (control, animals subjected to 1 ‰ thiourea, animals subjected to 4 × 10(-4) mL/L herbicide and, respectively, animals subjected to 4 × 10(-4) mL/L herbicide and 1 ‰ thiourea). Exposure of European chub to herbicide administered in water for 2 weeks determined installation of pathological changes in the liver and gills tissues. Also, were observed a decrease in the number of white blood cells and oxygen consumption, breathing frequency, and an increase in the number of red blood cells and glycaemia values. Thiourea counteracts the toxic action, describing itself as normal liver parenchyma and normal gills in animals intoxicated with herbicide, without lesion, and a return to normal values of the studied markers.

The influence of irradiation on autophagy process in normal and malignant colorectal epithelia.

AIM: The authors assessed the influence of preoperative radiotherapy on autophagy process using a quantitative assessment of LC3 expression on both normal and tumoral colorectal tissues. MATERIALS AND METHODS: Normal and malignant tissue samples were taken from 50 patients that underwent surgery for colorectal adenocarcinoma of which 11 received preoperative radiotherapy. Tissue samples were included in paraffin and sections were immunomarked for LC3 expression. LC3 percentage was assessed with dedicated software on 10 randomly selected fields with 40× objective from both normal and malignant tissue samples of each patient. The resulting data were assessed and compared with a statistical apparatus. RESULTS: LC3 was overexpressed in tumoral tissue as compared with normal one. The LC3 percentage is different from person to person and the higher it is in normal epithelium, the higher will be in tumoral epithelium of the same person, regardless the irradiation. The LC3 expression levels are decreasing from tumoral non-irradiated epithelia to normal irradiated epithelia. LC3 expression in tumoral cells is granular, with particular perinuclear disposal and often "annular" pattern. CONCLUSIONS: The autophagy process has a basal level in the normal tissue, with interindividual variability. The autophagy process proved to be upregulated in the tumoral cells, with a particular morphological expression, namely the presence of cytoplasmic coarse granules disposed in an "annular" pattern. Preoperative radiotherapy is downregulating the autophagy process both in normal and tumoral tissue but to a lesser extent in the latter.

Comparison of the Efficacy of Atopalm(®) Multi-Lamellar Emulsion Cream and Physiogel(®) Intensive Cream in Improving Epidermal Permeability Barrier in Sensitive Skin.

INTRODUCTION: The management of sensitive skin, which affects over 60% of the general population, has been a long-standing challenge for both patients and clinicians. Because defective epidermal permeability barrier is one of the clinical features of sensitive skin, barrier-enhancing products could be an optimal regimen for sensitive skin. In the present study, we evaluated the efficacy and safety of two barrier-enhancing products, i.e., Atopalm (®) Multi-Lamellar Emulsion (MLE) Cream and Physiogel (®) Intensive Cream for sensitive skin. METHODS: 60 patients with sensitive skin, aged 22-40 years old, were randomly assigned to one group treated with Atopalm MLE Cream, and another group treated with Physiogel Intensive Cream twice daily for 4 weeks. Lactic acid stinging test scores (LASTS), stratum hydration (SC) and transepidermal water loss (TEWL) were assessed before, 2 and 4 weeks after the treatment. RESULTS: Atopalm MLE Cream significantly lowered TEWL after 2 and 4 weeks of treatment (p < 0.01). In contrast, Physiogel Intensive Cream significantly increased TEWL after 2 weeks of treatment (p < 0.05) while TEWL significantly decreased after 4-week treatments. Moreover, both Atopalm MLE Cream and Physiogel Intensive Cream significantly increased SC hydration, and improved LASTS after 4 weeks of treatment. CONCLUSION: Both barrier-enhancing products are effective and safe for improving epidermal functions, including permeability barrier, SC hydration and LASTS, in sensitive skin. These products could be a valuable alternative for management of sensitive skin. FUNDING: Veterans Affairs Medical Center, San Francisco, California, USA, and NeoPharm Co., Ltd., Daejeon, Korea.

Prevalence and histopathological types of skin carcinomas in Arges County, Romania.

Non-melanoma skin cancers presented a significant incidence increase in the last decades, worldwidely. Even though the impact upon mortality is a relatively low one, through the incidence increase, their impact upon the public healthcare systems is a considerable one. In our study, we evaluated 109 cases of skin carcinomas hospitalized during 2012 in the Department of Plastic Surgery of the Emergency Hospital of Pitesti, Romania, for a surgical treatment. The gender distribution showed slight lesion predominance in women, being recorded 56 (51.38%) tumors in women and 53 (48.62%) in men. The highest incidence of skin carcinomas (75.23%) was recorded in the persons aged over 60-year-old. Of 109 cases of skin carcinomas, 80 (73.4%) carcinomas developed on indignant tegument areas, while 29 (26.6%) on premalignant skin lesions (fiberconjunctive papillomas, keratocantomas, keratosic verrucas). The histopathological study highlighted the fact that of 109 skin carcinomas, 87 (79.82%) were basal cell carcinomas and only 22 (20.18%) were squamous cell carcinomas. The immunohistochemical reaction to 34ßE12 cytokeratin was highly positive in the cells of the basal cell carcinomas and well-differentiated squamous cell carcinomas (except for the "keratosic pearls") and moderately positive in the moderately differentiated squamous cell carcinoma.

Topical hesperidin prevents glucocorticoid-induced abnormalities in epidermal barrier function in murine skin.

Systemic and topical glucocorticoids (GC) can cause significant adverse effects not only on the dermis, but also on epidermal structure and function. In epidermis, a striking GC-induced alteration in permeability barrier function occurs that can be attributed to an inhibition of epidermal mitogenesis, differentiation and lipid production. As prior studies in normal hairless mice demonstrated that topical applications of a flavonoid ingredient found in citrus, hesperidin, improve epidermal barrier function by stimulating epidermal proliferation and differentiation, we assessed here whether its topical applications could prevent GC-induced changes in epidermal function in murine skin and the basis for such effects. When hairless mice were co-treated topically with GC and 2% hesperidin twice-daily for 9 days, hesperidin co-applications prevented the expected GC-induced impairments of epidermal permeability barrier homoeostasis and stratum corneum (SC) acidification. These preventive effects could be attributed to a significant increase in filaggrin expression, enhanced epidermal ß-glucocerebrosidase activity and accelerated lamellar bilayer maturation, the last two likely attributable to a hesperidin-induced reduction in stratum corneum pH. Furthermore, co-applications of hesperidin with GC largely prevented the expected GC-induced inhibition of epidermal proliferation. Finally, topical hesperidin increased epidermal glutathione reductase mRNA expression, which could counteract multiple functional negative effects of GC on epidermis. Together, these results show that topical hesperidin prevents GC-induced epidermal side effects by divergent mechanisms.

Topical apigenin alleviates cutaneous inflammation in murine models.

Herbal medicines have been used in preventing and treating skin disorders for centuries. It has been demonstrated that systemic administration of chrysanthemum extract exhibits anti-inflammatory properties. However, whether topical applications of apigenin, a constituent of chrysanthemum extract, influence cutaneous inflammation is still unclear. In the present study, we first tested whether topical applications of apigenin alleviate cutaneous inflammation in murine models of acute dermatitis. The murine models of acute allergic contact dermatitis and acute irritant contact dermatitis were established by topical application of oxazolone and phorbol 12-myristate 13-acetate (TPA), respectively. Inflammation was assessed in both dermatitis models by measuring ear thickness. Additionally, the effect of apigenin on stratum corneum function in a murine subacute allergic contact dermatitis model was assessed with an MPA5 physiology monitor. Our results demonstrate that topical applications of apigenin exhibit therapeutic effects in both acute irritant contact dermatitis and allergic contact dermatitis models. Moreover, in comparison with the vehicle treatment, topical apigenin treatment significantly reduced transepidermal water loss, lowered skin surface pH, and increased stratum corneum hydration in a subacute murine allergic contact dermatitis model. Together, these results suggest that topical application of apigenin could provide an alternative regimen for the treatment of dermatitis.