Necrotizing fasciitis arising from squamous cell carcinoma of the vulva.

Necrotizing fasciitis (NF) is a devastating soft tissue infection affecting fascias and subcutaneous soft tissues. While it is associated with several risk factors, including malignancy, alcoholism, liver disease, drug use, malnutrition, diabetes, male gender and old age, few case reports in the literature describe its rare connection with genital malignancy. Vulvar squamous cell carcinoma (SCC) is the fourth most common malignancy, representing 5% of all gynaecological tumours among women. NF due to vulvar SCC is a rare complication. In this article, we present the 1991 case of a 58-year-old diabetic female patient with NF due to vulvar SCC. While surgical intervention was successful, the prognosis for vulvar SCC was poor because of late detection.

Can transcription factors in the intervertebral disc of lopinavir/ritonavir prevent degeneration in the nucleus pulposus by mediating the regulation of inflammation through signaling pathways?

OBJECTIVE: This study was conducted to examine whether lopinavir/ritonavir (Lop/r), an HIV protease inhibitor, can improve disc physiology and slow down intervertebral disc (IVD) degeneration through in vitro experimental methods, as well as whether it can suppress inflammation with interleukin-1 beta (IL-1ß) and sex-determining region Y (SRY) protein-related high-mobility group box genes-9 (SOX9) through hypoxia-inducible factor 1-alpha (HIF-1α) and the nuclear factor kappa B (NF-κB) signaling pathway. The aim was to investigate whether Lop/r application is toxic to IVD cells and the microenvironment simultaneously. PATIENTS AND METHODS: Human primary cell cultures were prepared using herniated IVD tissues obtained from patients with lumbar disc hernia who were unresponsive to conservative and medical treatment, and thereby, were operated on. The untreated culture samples served as control group, and the samples treated with Lop/r served as study group. Microscopic evaluations were performed simultaneously using fluorescent and supravital dyes in all groups. In addition to cell viability, toxicity, and proliferation analysis through a commercial kit, IL-1ß, SOX9, HIF-1α, and NF-κB protein expressions were evaluated using Western blotting. In the statistical comparison of the obtained data, an alpha value less than 0.05 was considered significant. RESULTS: Cell proliferation decreased in the Lop/r group, but no cell death was observed (p < 0.05). Moreover, at the end of 72 hours after Lop/r application, IL-1ß and NF-kB protein expressions decreased by 40% and 52%, respectively, while HIF-1α and SOX9 protein expressions increased by 4% and 59%, respectively (p< 0.05). CONCLUSIONS: Although these data were obtained from an in vitro experimental study, it is believed that these findings could make significant contributions to the pharmaco-regenerative treatment modalities of IVD degeneration. Lop/r suppresses the IL-1ß and NF-κB and induces SOX9 and HIF-1α, since these signaling pathways may be related to human IVD degeneration.

Does oseltamivir protect human chondrocyte and nucleus pulposus cells from degeneration by inhibiting senescence and proinflammation mediated by the NLRP3 inflammasome and NF-κB?

OBJECTIVE: Recent drug design studies suggest that inflammation is among the most important factors in the development of both intervertebral disc (IVD) degeneration (IVDD) and osteoarthritis (OA) due to cartilage damage. This study aimed to investigate whether the anti-inflammatory drug oseltamivir has a toxic effect on IVD and cartilage tissue cells. It assessed what effect oseltamivir has on hypoxia-inducible factor (HIF)-1 alpha (HIF1α), which plays an important role in anabolic pathways in IVD and cartilage tissue. In addition, the study analyzed whether oseltamivir could inhibit the release of inflammatory interleukin-1 beta (IL-1ß) via the nuclear factor kappa-B (NF-κB) signaling pathway by activating the nucleotide-binding oligomerization domain and leucine-rich repeat protein-3 (NLRP3) inflammasome. MATERIALS AND METHODS: Human lumbar IVD (n = 8) tissues were isolated for annulus fibrosus (AF) and nucleus pulposus (NP) primary cell cultures, and human tibial and femoral cartilage tissues (n = 8) were isolated for primary chondrocyte cultures. Untreated groups served as the control and oseltamivir-treated groups as the study sample. Cell viability and cytotoxicity were evaluated at 0, 24, 48, and 72 h in all groups for changes in HIF-1α, IL-1ß, NF-κB, and the NLRP3-inflammasome protein expressions using Western blotting. The α significance value was < 0.05. RESULTS: In the oseltamivir-treated groups, cell proliferation decreased in both AF/NP cell and chondrocyte cultures obtained from IVD cartilage tissues. After Western blotting analysis, changes were observed in the protein expressions of HIF-1α, IL-1ß, NF-κB, and the NLRP3 inflammasome in both AF/NP cells and chondrocytes. The results were statistically significant (p < 0.05). CONCLUSIONS: Oseltamivir treatment may be a promising regenerative strategy to manage IVDD and osteoarthritic cartilage tissues.

Effects of an acetylcholinesterase inhibitor and an N-methyl-D-aspartate receptor antagonist on inflammation and degeneration of the nucleus pulposus.

OBJECTIVE: The study aimed to examine the effects of two drugs, an acetylcholinesterase inhibitor (AChEI) and an N-methyl-D-aspartate receptor (NMDAR) antagonist, on degenerated annulus fibrosus (AF) and nucleus pulposus (NP) cells and the extracellular matrix (ECM) structure in vitro. PATIENTS AND METHODS: Tissue samples were obtained from patients with intervertebral disc herniation (four males and four females; classified as Pfirmann stage IV) and used to prepare cell cultures. Untreated cell culture samples served as the control group. Study group samples were treated with donepezil, memantine or a combination of the two drugs. Cell viability, toxicity and proliferation were evaluated in all groups. Western blotting was used to examine changes in protein expression of signal transducer and activator of transcription 3 (STAT3), phospho-STAT3 (ser727), hypoxia-inducible factor (HIF)-1 alpha (HIF-1α) and nucleotide-binding oligomerisation domain (NOD) leucine-rich repeat (LRR)-containing proteins (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. The alpha significance value was < 0.05. RESULTS: Analysis of the microscopy and commercial kit results revealed that cell proliferation was suppressed, and no cell death was observed. The protein expression levels of NLRP3, STAT3, ser727 and HIF-1α were lower in the samples treated with donepezil and memantine at 72 h (p < 0.05). The protein expression levels of NLRP3, STAT3, ser727 and HIF-1α were higher in the samples treated with the combination of donepezil and memantine (p < 0.05). CONCLUSIONS: The combined administration of memantine a NMDAR antagonist which can prevent neurodegeneration and donepezil an AChEI used for pain relief increased the protein expression levels in the anabolic pathway. However, it did not reduce the protein expression levels in the catabolic pathway. Therefore, further studies are needed to provide extensive insight into whether it may be among the potential targets for the therapy of intervertebral disc (IVD) diseases.

In-transit metastasis of cutaneous squamous cell carcinoma: report of two cases.

Transit metastases include metastatic foci of the skin and subcutaneous tissue located between the tumor and the nearest regional lymph node. Although transit metastases have been described for malignant melanoma, some cases of transit metastases have also been reported among primary cutaneous non-melanoma cancers. Treatment of patients with in-transit squamous cell carcinoma (SCC) is a multimodal approach for advanced staging imaging and therapy, including Mohs micrographic surgery, adjuvant radiation, and possibly sentinel lymph node biopsy and immunotherapy or chemotherapy. Here we report two cases of in-transit metastasis with primary cutaneous SCC.

Venous Lakes of the Lips Successfully Treated With a Sclerosing Agent 1% polidocanol: analysis of 25 report cases.

BACKGROUND: Venous lakes of the lip is vascular ectasia that generally appears on the lower lip and other sun-damaged surfaces of skin in elderly patient. There are many local therapies for treatment of lip venous lake such as surgical excision, cryotherapy, infrared coagulation and laser therapy. Sclerotherapy as treatment is used in varicose veins, leg telangiectasia, hemorrhoids and hemangiomas but for lip venous lake only two case has been reported. Therefore, we managed this study to determine the efficacy of injection of 1% polidocanol in the treatment of venous lake lesions. METHODS: This is retrospective study. Twenty five adult patient presenting with several localizations of venous lake were enrolled in the study. Informed consent was given before the treatment and a photo of the venous lake was taken. After the lesion was cleaned with an antiseptic, was slowly injected 1% polidocanol into each patient's lesion, followed by compression for 5 min. Visual Analog Scale (VAS) scale was used to indicate patient satisfaction. RESULT: Lesions were completely cleared in all patients after treatment. The lesions generally disappeared in two cases leaving an insignificant scar, in two cases become angioedema with two sessions of sclerotherapy. In other cases side effects were not observed. CONCLUSION: Sclerotherapy with polidocanol is an easy, inexpensive method and is found very effective in the treatment of lip venous lake. In the future it offers an alternative to other classic methods.

Pharmaco-molecular assessment of the effects of anandamide and its antagonists on hippocampal tissue in Wistar albino rats.

OBJECTIVE: The members of the matrix metalloproteinase (MMP) family and cannabinoids (CBs) are reportedly associated with hippocampus-dependent memory functions. However, the effects of endogenously formed CBs on hippocampal long-term potentiation remain unknown. The present study aimed to investigate the changes in the gene and protein expression levels of matrix metallopeptidase 9 (MMP-9), phosphatase and tensin homolog (PTEN), and NOTCH receptor 1 (NOTCH1) in rat hippocampal tissues treated with anandamide (AEA), AM251, 6-iodopravadolin (AM630), and N-[4-{[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl}phenyl] (ML193). MATERIALS AND METHODS: The subjects were divided into 10 groups (n = five per group). The pharmaceuticals were administered via intraperitoneal injection once a day for seven days, except for the control group. The resected hippocampal tissues were then evaluated using a quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analysis. The data obtained were statistically analyzed, and p < 0.01 was considered statistically significant. RESULTS: Contrary to the literature, the changes in MMP-9 expression were not statistically significant, but the changes in PTEN and NOTCH1 were. The findings of this in vivo experimental study revealed that the agonists and antagonists acting on the CB system have significant molecular effects on hippocampal tissue. CONCLUSIONS: The changes in gene and protein expressions may be one of the reasons for the neurodegenerative processes observed in patients using these agonists and antagonists, whose effects on the CB system have not been fully explained yet. Our study can contribute to the literature as it is the first study investigating the MMP-9, PTEN and NOTCH1 gene and protein expression.

A Controlled Study to Examine the Effect of Topical Sucralfate on Radiofrequency-induced Burn Wounds in Rats

Several preclinical studies have shown topical sucralfate facilitates wound repair. PURPOSE: This study aimed to evaluate the effect of 10% topical sucralfate on healing radiofrequency-induced burn wounds in rats. METHODS: Twenty (20) male rats were divided into 2 equal groups. Using radiofrequency, 4 full-thickness, 1 cm in diameter round burns were created on the backs of the rats that then were randomized to receive twice-daily treatment for 30 days with 10% sucralfate or neutral cream. Biopsies were taken on days 4, 7, 14, and 21 to analyze fibrin-leukocyte crut, edema density, epidermal-dermal cell infiltration, amount of fibroblast and collagen fibers, amount of elastic fibers, neovascularization-angiogenesis, and reepithelialization-granulation tissue. Data were collected to a spreadsheet and entered into statistical software for analysis. Histopathological features were classified as categorical variables and compared using the χ2 test and Fisher's exact test. When χ2 was used, Yates' correction for continuity was performed. All reported P values were 2-tailed; P less than .05 was considered statistically significant. RESULTS: On day 4, improvement in edema density (P = .034), epidermal detachment (P = .020), epidermal-dermal cell infiltration (P = .007), and polymorphonuclear leukocyte infiltration (P = .021) were statistically more significant in the sucralfate than control group. On day 7, epidermal-dermal cell infiltration (P = .007) and elastic fibers P = .050) were statistically more significant in the sucralfate group. On day 14, angiogenesis (P = .029), reepithelialization (P = .035), and granulation tissue (P = .003) were statistically more significant in the sucralfate group. By the end of the study (day 30), angiogenesis (P = .010), reepithelialization (P <.001), fibroblast density (P = .016), granulation tissue (P = .035), and collagen density (P = .002) were significantly improved in the sucralfate group versus the control group. CONCLUSION: In a rat wound model, 10% topical sucralfate was found to histopathologically facilitate the healing process compared to the control group. Controlled clinical studies are needed to elucidate the effect of this treatment in human wounds.

Telangiectatic Carcinoma - Like Lymphangioma Circumscriptum. A Rare Form of Cutaneous Metastasis of Breast Carcinoma: Case Report.

INTRODUCTION: The Breast cancer is the most common malignancy in middle-aged women and that causes skin metastasis. Skin metastasis in internal cancer cases is a very rare condition and may be difficult to diagnose and have poor prognostic marker. Cutaneous metastasis of breast carcinoma is mostly seen as direct invasion and/or local infiltration. However, in addition to the well-known types, cutaneous metastases may mimic many benign skin lesions and therefore may be difficult to diagnose. CASE REPORT: In this article we present a 36-year-old woman with telangiectatic carcinoma-like lymphangioma circumscriptum, a rare form of cutaneous metastasis skin metastases. It can be the first sign of internal malignancies, so early diagnosis is very important at this stage. CONCLUSION: Therefore, solitary lesions or benign dermatoses seen in the skin and not associated with specific disease should be considered as tumor metastasis especially in female patients with a history of breast cancer and differential diagnosis must be made.

Melatonin reverses the oxidative stress and mitochondrial dysfunction caused by LETM1 silencing.

LETM1 is a mitochondrial inner-membrane protein, which is encoded by a gene present in a locus of 4p, which, in turn, is deleted in the Wolf-Hirschhorn Syndrome, and is assumed to be related to its pathogenesis. The cellular damage caused by the deletion is presumably related to oxidative stress. Melatonin has many beneficial roles in protecting mitochondria by scavenging reactive oxygen species, maintaining membrane potential, and improving functions. The aim of this study was to investigate the effects of melatonin administration to LETM1-silenced mouse embryonic fibroblast cells as a cellular model for LETM1 deficiency. We transfected mouse embryonic fibroblast cells with a pair of siRNA against LETM1 and monitored the oxidative stress and mitochondrial functions with or without melatonin addition. MnSOD expression and aconitase activity decreased and oxidized protein levels increased in LETM1-silenced cells. LETM1 suppression did not alter the expression of OXPHOS complexes, but the oxygen consumption rates decreased significantly; however, this change was not related to complex I but instead involved complex IV and complex II. Melatonin supplementation effectively normalized the parameters studied, including the oxygen consumption rate. Our findings identified a novel effect of LETM1 deficiency on cellular respiration via complex II as well as a potential beneficial role of melatonin treatment. On the other hand, these effects may be specific to the cell line used and need to be verified in other cell lines.

An Uncommon Coexistence of Sarcoidosis and Cutaneous Leukocytoclastic Vasculitis in an Adult.

The skin is the second most commonly involved organ after pulmonary system in sarcoidosis, a multisystemic granulomatous disease. Cutaneous small-vessel vasculitis (leukocytoclastic vasculitis [LCV]) is a disorder characterized by neutrophilic inflammation of small blood vessels. Although the skin is the organ where LCV is seen most frequently, extracutaneous involvements are also seen. Herein, we present a coexistence of sarcoidosis and cutaneous LCV, which is an uncommon condition in adult.

Are radio-contrast agents commonly used in discography toxic to the intact intervertebral disc tissue cells?

In the literature, there have been no studies showing clear results on how radio-contrast pharmaceuticals would affect intact disc tissue cells. In this context, it was aimed to evaluate the effects of iopromide and gadoxetic acid, frequently used in the discography, on intact lumbar disc tissue in pharmaco-molecular and histopathological level. Primary cell cultures were prepared from the healthy disc tissue of the patients operated in the neurosurgery clinic. Except for the control group, the cultures were incubated with the indicated radio-contrast agents. Cell viability, toxicity and proliferation indices were tested at specific time intervals. The cell viability was quantitatively analysed. It was also visually rechecked under a fluorescence microscope with acridine orange/propidium iodide staining. Simultaneously, cell surface morphology was analysed with an inverted light microscope, while haematoxylin and eosin (H&E) staining methodology was used in the histopathological evaluations. The obtained data were evaluated statistically. Unlike the literature, iopromide or gadoxetic acid did not have any adverse effects on the cell viability, proliferation and toxicity (P < 0.05). Although this study reveals that radio-contrast pharmaceuticals used in the discography, often used in neurosurgical practice, can be safely used, it should be remembered that this study was performed in an in vitro environment.

Topical sucralfate cream treatment for aplasia cutis congenita with dystrophic epidermolysis bullosa: a case study.

Bart syndrome consists of aplasia cutis congenita (ACC) and dominant or recessive dystrophic epidermolysis bullosa (DEB), associated with skin fragility and nail dysplasia. ACC in DEB is thought to be caused by trauma, the most cited cause being in utero formation of bullae consequent to friction of the limbs. Epidermolysis bullosa (EB) refers to a hereditary mechanobullous disease following trauma, characterised by formation of blisters on the skin and mucous membranes. There are four categories of the disease, including epidermolysis bullosa simplex, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa and Kindler syndrome. Infection, sepsis and death may occur as a consequence of generalised blistering with complication. We present the case of a newborn diagnosed with DEB and whose lesions became almost fully epithelialised after treatment with 10% topical sucralfate.

Effect of naproxen on proliferation and differentiation of primary cell cultures isolated from human cartilage tissue.

Non-steroidal anti-inflammatory drugs (NSAIDs) that are applied through oral, injectable or topical routes have been widely used in painful and inflammatory musculoskeletal diseases. The current study aimed to determine whether naproxen, an aryl acetic acid derivative with analgesic and anti-inflammatory effects, has a toxic effect on human chondrocytes. Samples containing monolayer primary chondrocyte cultures were prepared following resection from osteochondral tissues obtained from patients with gonarthrosis. Cell viability, toxicity and proliferation and levels of stage-specific embryonic antigen-1, a precursor to human prechondrocytes, were evaluated spectrophotometrically. The results from the untreated control group were compared with those of the study groups, where naproxen was administered in varying doses (1-1,000 µM). Surface morphologies of the cells were compared using inverted light and environmental scanning electron microscopy. Treatment groups were compared by analysis of variance with Tukey's honest difference post hoc test. P<0.01 was considered to indicate a statistically significant difference. The research revealed significant changes to proliferation and differentiation of chondrocytes in all treatment groups (P<0.01). Naproxen was demonstrated to suppress chondrocyte proliferation and differentiation, which may be an important factor to consider when prescribing this medication to patients.

Assessment of quality of life in Turkish children with psoriasis and their caregivers.

BACKGROUND/OBJECTIVES: The effect of pediatric psoriasis on quality of life has been demonstrated, but data regarding its influence on caregiver quality of life are scarce. The objective was to investigate how psoriasis affects quality of life of children and their caregivers. METHODS: This multicenter study included 129 children with psoriasis and their caregivers, who were family members accompanying patients to the clinic. Patient quality of life was measured using the Child Dermatology Life Quality Index. Caregiver quality of life was assessed using Dermatological Family Impact Scale, a 15-item questionnaire validated for use in the Turkish language. RESULTS: Mean Child Dermatology Life Quality Index score was 7.6, indicating a moderate effect on patient quality of life. Symptoms and feelings were the most severely impaired domains of patient quality of life, and emotions was the most severely impaired domain of caregiver quality of life. Dermatological Family Impact Scale score was significantly correlated with Child Dermatology Life Quality Index (correlation coefficient [r] = .554, P < .001) and Psoriasis Area and Severity Index (r = .350, P < .001). Caregivers of patients receiving systemic agents or phototherapy had relative impairment of multiple domains of quality of life compared to caregivers of patients receiving topical treatment only. CONCLUSION: Psychosocial effect of pediatric psoriasis was shown to extend beyond the individual, highlighting the importance of addressing patient and caregiver quality of life concerns in an integrated approach.

Morphology, growth rate, and thickness of the nail plate during the pregnancy.

Pregnancy causes some physiological skin changes, such as hyperpigmentation and striae gravidarum. Thickening of scalp hair and a prolonged anagen phase are also known to occur during pregnancy. However, a limited number of studies have been conducted on the effect of pregnancy on the nails. We aimed to investigate the effect of pregnancy on the morphology of the nail plate, specifically its growth rate and thickness. Pregnant women and a control group consisting of healthy female volunteers were included in the study. The distance from the apical point of the lunula to the midpoint of the free edge of the nail plate of the the thumb was measured with digital calipers. The measurement was repeated during the control visits and recorded in millimeters per day. The thickness of the nail plate of the thumb was measured at the midpoint of the free edge of the nail plate. A dermatological examination of the fingernails was performed for both groups. A survey was also conducted to identify any changes that occurred in the nails during pregnancy. The mean growth rate of the nail plate in pregnant women was 0.1 ± 0.05 mm/day, and in the control group it was 0.09 ± 0.05 mm/day. There was no statistically significant difference between the pregnant and control groups regarding the growth rate of the nail plate (P = 0.438). The mean thickness of the nail plate in pregnant women was 0.87 ± 0.19 mm, and in the control group it was 0.75 ± 0.17 mm. There was a statistically significant difference between the groups with respect to nail plate thickness (P < 0.001). A dermatological examination of the fingernails in the two groups did not reveal any statistically significant differences with respect to the nail findings. We determined in our study that pregnancy did not affect the growth rate and the morphology of the nails but increased the thickness of the nail plates.

A Rare Syndrome Resembling Scleroderma: Huriez Syndrome.

Huriez syndrome, also referred to as "sclerotylosis," is a rare autosomal dominant genodermatosis characterized by the triad of congenital scleroatrophy of the distal extremities, palmoplantar keratoderma, and hypoplastic nails. The development of aggressive squamous cell carcinoma (SCC) arising in the scleroatrophic area is also a distinctive feature of the syndrome. Early diagnosis is important due to the early onset, mostly in the third to fourth decades of life, and aggressive progress of SCC, which occurs in around 15% of affected individuals. Our patient had palmoplantar keratoderma, scleroatrophy of the hands, and hypoplastic nails. Her mother and father had a second-degree blood relation. Two of her siblings had similar complaints and findings. She showed no sign of actinic keratosis or SCC, and was called for regular follow-ups. With this case, we want to emphasize that Huriez syndrome is a rare genodermatosis, mimicking scleroderma-like acrosclerosis, and early diagnosis is critical for recognizing and preventing the development of SCC.

Poxvirus-Induced Vascular Angiogenesis Mimicking Pyogenic Granuloma.

The orf virus, a member of poxvirus family, is a zoonotic parapoxvirus endemic in many countries, mostly seen among sheep, goats, oxen, and may be transmitted to humans. Orf virus infections may induce ulceration, papulonodular, pustular, or ecthyma lesions in the skin. Rarely, orf virus provokes extensive vasculoendothelial proliferation by encoding an apparent homolog of the mammalian vascular endothelial growth factor family of molecules. The vascular endothelial growth factor-like viral gene product is expressed early during infection and could be responsible for the induction of endothelial proliferation. Here, a 6-year-old male patient with poxvirus-induced widespread vascular angiogenesis is presented, which developed ten days after a thermal burn.

A Proposal for a New Severity Index for the Evaluation of Chronic Paronychia.

INTRODUCTION: Chronic paronychia (CP) is an inflammatory disease of the nail folds. Staging of CP is important for clinicians. We developed an objective scale that evaluates each finding of CP separately in addition to evaluating the treatment process and follow-up. METHODS: A new "chronic paronychia severity index scale" was developed to enable dermatologists to examine all features of CP. A previous categorical severity scale and this new scale were used for the evaluation of CP by 6 different dermatologists. The dermatologists evaluated the nails with both scales again 20 days later using randomly ordered photographs. RESULTS: Using the previous scale, the intra-observer intraclass correlation coefficient (ICC) values between the first and second evaluations were 0.767, 0.860, 0.734, 0.609, 0.900, and 0.840 for the 6 dermatologists. Using the new proposed scale, the intra-observer ICC values between the first and second evaluations were 0.930, 0.931, 0.942, 0.934, 0.938, and 0.920 for the 6 dermatologists. All intra-observer ICC values were higher for the results of the proposed scale than for those of the previous scale. The inter-observer ICC values were also higher for the proposed scale than for the previous scale for the 6 dermatologists. CONCLUSION: The new scale is a standardized, more suitable, objective, and valuable method to use in clinical practice and studies on CP.