The prophylactic and therapeutic impact of Trichinella spiralis larvae excretory secretory antigens- loaded Ca-BTC metal organic frameworks on induced murine colitis.

Background: Inflammatory bowel disease is an autoimmune disease that affects the gut. T. spiralis larvae (E/S Ags) loaded on calcium-benzene-1,3,5-tricarboxylate metal-organic frameworks (Ca-BTC MOFs) were tested to determine whether they might prevent or cure acetic acid-induced murine colitis. Methods: T. spiralis larvae E/S Ags/Ca-BTC MOFs were used in prophylactic and therapeutic groups to either precede or follow the development of murine colitis. On the seventh day after colitis, mice were slaughtered. The effect of our target antigens on the progress of the colitis was evaluated using a variety of measures, including survival rate, disease activity index, colon weight/bodyweight, colon weight/length) ratios, and ratings for macroscopic and microscopic colon damage. The levels of inflammatory cytokines (interferon-γ and interleukin-4), oxidative stress marker malondialdehyde, and glutathione peroxidase in serum samples were evaluated. Foxp3 T-reg expression was carried out in colonic and splenic tissues. Results: T. spiralis larvae E/S Ags/Ca-BTC MOFs were the most effective in alleviating severe inflammation in murine colitis. The survival rate, disease activity index score, colon weight/length and colon weight/bodyweight ratios, and gross and microscopic colon damage scores have all considerably improved. A large decrease in proinflammatory cytokine (interferon-γ) and oxidative stress marker (malondialdehyde) expression and a significant increase in interleukin-4 and glutathione peroxidase expression were obtained. The expression of Foxp3+ Treg cells was elevated in colonic and splenic tissues. Conclusion: T. spiralis larvae E/S Ags/Ca-BTC MOFs had the highest anti-inflammatory, antioxidant, and cytoprotective capabilities against murine colitis and might be used to develop new preventative and treatment strategies.

Subacute cutaneous lupus erythematosus and dermatomyositis associated with anti-programmed cell death 1 therapy.

Programmed cell death 1 (PD-1) blockade has rapidly emerged as an effective therapy for a wide variety of metastatic malignancies. It has been associated with multiple immune-related adverse effects, including cutaneous eruptions. We describe two patients with clinical and histological findings that were consistent with subacute cutaneous lupus erythematosus (SCLE) after receiving PD-1 inhibitor therapy for metastatic lung cancer. We successfully treated our first patient with systemic and topical steroids, photoprotection and hydroxychloroquine. However, he subsequently developed dermatomyositis after continuing PD-1 inhibitor therapy. Our second patient presented with a protracted course of a cutaneous eruption in spite of discontinuation of anti-PD-1 therapy and treatment with systemic corticosteroids and infliximab. This patient's SCLE resolved after the addition of topical steroids and photoprotection and discontinuation of anti-tumour necrosis factor therapy. She and her oncology team decided to pursue non-PD-1 inhibitor treatment for lung cancer owing to a lack of tumour response. We add SCLE and dermatomyositis to the growing list of autoimmune complications of PD-1 blockade. Our cases raise a number of questions, particularly in relation to the viability of continuing anti-PD-1 therapy after developing SCLE and the role of immunosuppressive therapy in patients with PD-1 inhibitor-associated connective tissue disease. What's already known about this topic? Programmed cell death 1 (PD-1) blockade, which is rapidly emerging as a therapy for a wide variety of metastatic malignancies, has been associated with multiple immune-related adverse effects. These include systemic autoimmune diseases such as colitis and thyroiditis in addition to numerous cutaneous adverse events. Cutaneous side-effects of PD-1 inhibitors most commonly reported in clinical trials include lichenoid reactions, eczematous dermatitis and vitiligo. What does this study add? We report two cases of PD-1 inhibitor-associated subacute cutaneous lupus erythematosus (SCLE), with one patient progressing to dermatomyositis with continued PD-1 inhibitor treatment. In addition to being a novel cutaneous adverse event, we also demonstrate the possibility of development of multiple autoimmune diseases in one patient, which is different from classic drug-related SCLE. We discuss the treatment challenges for patients with autoimmune skin disease receiving PD-1 inhibitor therapy.

Erythema dyschromicum perstans: A case report and systematic review of histologic presentation and treatment.

OBJECTIVE: Erythema dyschromicum perstans (EDP) can be difficult to diagnose and treat; therefore, we reviewed the literature to assess whether histology can be used to differentiate lichen planus pigmentosus (LPP) from EDP and determine which treatments are the most effective for EDP. We also present a case of a patient who was treated successfully with narrow-band ultraviolet B (NB-UVB). METHODS: A systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was conducted up to July 2017 using four databases. RESULTS: Histologic analyses from the literature reveal a significant percentage of melanophages, lymphocytic infiltrates, and basal vacuolar degeneration in EDP, and a significant histologic overlap with LPP. The review of the literature on treatment outcomes showed that NB-UVB and tacrolimus were effective with minimal side effects. Clofazimine was effective, but demonstrated significant-to-intolerable side effects. Griseofulvin, isotretinoin, and dapsone provided unsatisfactory results as lesions recurred after discontinuation. Lasers were largely ineffective and may cause postinflammatory hyperpigmentation and fibrosis. CONCLUSION: A diagnosis of EDP should not be based on histologic findings alone. Clinical history, morphology, and distribution should be used to differentiate EDP and LPP. NB-UVB and tacrolimus are promising treatments for EDP with minimal side effects. This is the first report to our knowledge of sustained resolution of EDP after treatment with NB-UVB at long-term follow-up of 4 years. Larger studies are needed to confirm these findings.

KIT mutations and CD117 overexpression are markers of better progression-free survival in vulvar melanomas.

BACKGROUND: Few studies have addressed prognostic markers and none has correlated molecular status and prognosis in vulvar melanomas. OBJECTIVES: To evaluate the clinicopathological features of 95 cases of vulvar melanoma. METHODS: p53, CD117, Ki-67, neurofibromin, brafv600e and nrasq61r immunostains, and molecular analyses by either targeted next-generation or direct sequencing, were performed on available archival materials. RESULTS: Molecular testing detected mutations in KIT (44%), BRAF (25%), NF1 (22%), TP53 (17%), NRAS (9%) and TERT promoter (9%). Co-mutation of KIT and NF1 and of KIT and NRAS were identified in two and one cases, respectively. KIT mutations were significantly associated with better progression-free survival in univariate analyses. In multivariate analyses CD117 expression was significantly associated with better progression-free survival. Tumour thickness was significantly associated with worse progression-free and overall survival, and perineural invasion significantly correlated with reduced melanoma-specific survival and reduced overall survival. Cases were from multiple centres and only a subset of samples was available for molecular testing. CONCLUSIONS: KIT mutations and CD117 overexpression are markers of better progression-free survival. In addition to its prognostic value, molecular testing may identify cases that might respond to targeted agents or immunotherapeutic approaches.

Occurrence, genotyping, shiga toxin genes and associated risk factors of E. coli isolated from dairy farms, handlers and milk consumers.

The objectives of the current study were to determine the occurrence and genotypes of E. coli in dairy farms, workers and milk consumers and to evaluate risk factors associated with contamination of milk in dairy farms. Molecular characterization of shiga toxin associated genes and enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) finger printing of E. coli from different sources were also studied. Paired milk samples and rectal swabs from 125 dairy cows, rectal swabs from 82 calves and hand swabs from 45 dairy workers from five dairy farms were collected. In addition, 100 stool samples from 70 diarrheic and 30 healthy humans were collected and examined for the presence of E. coli. E. coli was isolated from milk (22.4%), dairy cattle feces (33.6%), calf feces (35.4%), dairy worker hand swabs (11.1%) and stools of milk consumers (2%, from diarrheic patients only). Only stx1 was identified in seven of 12 E. coli O125 isolated from different sources. High genetic diversity was determined (Simpson's index of diversity, D = 1) and E. coli O125 isolates were classified into 12 distinct profiles, E1-E12. The dendrogram analysis showed that two main clusters were generated. Mastitis in dairy cows was considered a risk factor associated with contamination of the produced milk with E. coli. The isolation of E. coli from rectal swabs of dairy cows and calves poses a zoonotic risk through consumption of unpasteurized contaminated dairy milk. Educational awareness should be developed to address risks related to consumption of raw milk.

A phase I multi-institutional study of systemic sorafenib in conjunction with regional melphalan for in-transit melanoma of the extremity.

BACKGROUND: Isolated limb infusion with melphalan (ILI-M) corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximate 29 % complete response (CR) rate. Sorafenib, a multi-kinase inhibitor, has been shown to augment tumor response to chemotherapy in preclinical studies. METHODS: A multi-institutional, dose-escalation, phase I study was performed to evaluate the safety and antitumor activity of sorafenib in combination with ILI-M. Patients with AJCC stage IIIB/IIIC/IV melanoma were treated with sorafenib starting at 400 mg daily for 7 days before and 7 days after ILI-M corrected for IBW. Toxicity, drug pharmacokinetics, and tumor protein expression changes were measured and correlated with clinical response at 3 months. RESULTS: A total of 20 patients were enrolled at two institutions. The maximum tolerated dose (MTD) of sorafenib in combination with ILI-M was 400 mg. Four dose-limiting toxicities occurred, including soft tissue ulcerations and compartment syndrome. There were three CRs (15 %) and four partial responses (20 %). Of patients with the Braf mutation, 83 % (n = 6) progressed compared with only 33 % without (n = 12). Short-term sorafenib treatment did alter protein expression as measured with reverse phase protein array (RPPA) analysis, but did not inhibit protein expression in the MAP kinase pathway. Sorafenib did not alter melphalan pharmacokinetics. CONCLUSION: This trial defined the MTD of systemically administered sorafenib in combination with ILI-M. Although some responses were seen, the addition of sorafenib to ILI-M did not appear to augment the effects of melphalan but did increase regional toxicity.

Familial eruptive vellus hair cysts.

Eruptive vellus hairs cysts are benign papules consisting of small cysts containing multiple vellus hairs. An eruption commonly develops on the chest and sometimes the upper extremities. These papules are asymptomatic or rarely pruritic. Only a few cases of familial association have been described. We report the development of eruptive vellus hair cysts on the trunk of an 8- and 12-year-old sister and brother.

Screening of marine extracts for schistosomicidal activity in vitro. Isolation of the triterpene glycosides echinosides A and B with potential activity from the Sea Cucumbers Actinopyga echinites and Holothuria polii.

CONTEXT: Praziquantel (PZQ) is the drug available for the treatment of schistosomiasis. The reported reduced cure rates, the failure of treatment after PZQ administration in patients and the existence of resistant parasite strains, reinforce the need to rapidly discover new effective molecules against Schistosoma parasite. OBJECTIVE: To screen the methanol extracts of 79 marine organisms for their schistosomicidal activities against Schistosoma mansoni adult worms in vitro and perform bio-assay directed chromatography for the most active extracts to isolate the active compounds. MATERIALS AND METHODS: Screening of the marine organisms and bio-assay directed chromatography of the most active extracts together with identification of the active isolates using 1D and 2D NMR analysis, were investigated. RESULTS: RESULTS indicated that the isolates echinosides A and B from the sea cucumbers Actinopyga echinites Jaeger and Holothuria polii Delle Chiaie (Holothuriidae) were highly active. Their LC(50) values were equal to 0.19 µg/ml and 0.27 µg/ml, respectively. Detailed (1)HNMR data for echinosides A and B are reported here for the first time. DISCUSSION AND CONCLUSION: These findings demonstrate that the isolated echinosides possess potential in vitro schistosomicidal activity against S. mansoni adult worms. Therefore, echinosides are promising as lead compounds for the development of new schistosomicidal agents.

Cytotoxic triterpenoid saponins acylated with monoterpenic acids from fruits of Gleditsia caspica Desf.

Four bisdesmosidic triterpenoid saponins named caspicaosides A-D, were isolated from the fruits of Gleditsia caspica Desf. Their structures were determined by NMR spectroscopy including HOHAHA, ¹H-¹H COSY, ROE, HMQC, HMBC experiments and HRFAB-MS as well as acid hydrolysis. The four 3,28-O-bisdesmosidic triterpenoid saponins comprised echinocystic acid as the aglycone and common oligosaccharide moieties at C3 and C28. The saccharide moiety at C-3 was identified as ß-D-xylopyranosyl-(1→2)-α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranosyl while that at C-28 was determined as ß-D-xylopyranosyl-(1→3)-ß-d-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→6)-]ß-D-glucopyranosyl. The pentasaccharide moiety linked to C-28 was acylated with monoterpenic acid and or monoterpene-arabinoside moieties at C-2 or C-2 and C-3 of the terminal rhamnose unit. The isolated saponins were assayed for their in vitro cytotoxicities against the three human tumor cell lines HepG2, A549 and HT29 using MTT method. The results showed that caspicaosides B and C bearing two and three monoterpene units, respectively, exhibited significant cytotoxic activities against the used cell lines with IC50 values 1.5-6.5 µM. Caspicaosides A and D with one monoterpene unit exhibited significant cytotoxic activities on HepG2 cell line with IC50 values equal to 4.5 and 5.4 µM, respectively, and IC50 values > 10 µM against the other two cell lines. The number of monoterpene units seems to play a main role in determining the activity.

Solvatochromic, acid-base features and time effect of some azo dyes derived from 1,3-benzothiazol-2-ylacetonitrile: experimental and semiempirical investigations.

The solvatochromism and other spectroscopic properties of seven azo dyes were studied, with a particular respect to the role of the solvent basicity, and interpreted with the aid of experimental findings and semiempirical data. The electronic absorption spectra of the dyes examined in different solvents combined with theoretical calculations showed that most of the investigated compounds coexist in the hydrazone and/or azo-enamine-common anion equilibrium or in the solely anionic form depending upon the nature of the solvent employed. These interesting features open up possibilities for the use of these compounds in analytical chemistry as acid-base indicators. Furthermore, both of intermolecular and intramolecular charge transfer equilibria have been reflected by experimental absorption spectra of compounds 4 and 5. The enthalpies of formation predicted at PM6 (COSMO) and PM6/CI (COSMO) for the ground (S(0)) and excited (S(1)) states, respectively have been successfully used for the explanation of the observed bathchromic shift in non-polar solvents. The effect of time on the longer wavelength visible band of compound 7 has been thoroughly investigated.

Seasonal variation of the lipoidal matters and hypolipidaemic activity of the red alga Corallina officinalis L.

The lipoidal matters of Corallina officinalis L. showed a seasonal nonsignificant quantitative variation. However, the fatty acids revealed a relative increase in the summer and winter, while unsaponifiable matter exhibited a slight increase in the spring. The GC/MS analysis of saponifiable and unsaponifiable matter of the algal samples collected in different seasons revealed that samples collected in the spring contained a low cholesterol content and high steroidal compounds as well as high polyunsaturated fatty acids. The alcohol extract, hexane extract and fatty acid fraction of this algal sample exhibited a significant hypolipidaemic activity. Also, two biologically active fractions of hydrocarbons were isolated by CC technique from the hexane fraction of C. officinalis L. and identified by GC/MS.

CD34 expression in desmoplastic melanoma.

BACKGROUND: Primary and metastatic malignant melanoma can simulate various soft tissue tumors, including dermatofibrosarcoma protuberans (DFSP). Expression of CD34, a marker characteristic of DFSP, as well as other spindle cell tumors, has not been previously documented in malignant melanoma. METHODS: We present here an unusual case of metastatic malignant melanoma with a strong histologic resemblance to DFSP and also CD34 expression. RESULTS: The patient, a 72-year-old man with a history of an invasive malignant melanoma of the skin of the right lower abdomen, presented with a right axillary mass. Histologic sections revealed intersecting fascicles of spindle cells with nuclear pleomorphism and numerous mitotic figures, diffusely infiltrating the adipose tissue in a pattern closely simulating that seen in DFSP. In other foci, epithelioid neoplastic cells with abundant cytoplasm, prominent nucleoli, nuclear pseudoinclusions, and focal cytoplasmic melanin pigment were seen. The neoplastic spindle cells were strongly labeled by two anti-CD34 monoclonal antibodies. Some of the spindle cells and the majority of the epithelioid neoplastic cells expressed S-100 protein and focally tyrosinase. The tumor cells were negative for HMB-45 and MART-1. Melanosomes were not identified by electron microscopy. CONCLUSION: This case demonstrates the potential of melanoma to simulate DFSP closely, on both morphologic and immunohistochemical grounds, and confirms the utility of employing a broad panel of immunohistochemical reagents in problematic cases.

Waxy keratoses of childhood in a segmental distribution.

Waxy keratoses of childhood is a rare genodermatosis previously noted in both familial and isolated presentations. Three previous cases have been described in which the lesions appeared over the trunk and extremities. We report a case in which the waxy keratoses of childhood lesions appeared in a segmental distribution along a single lower extremity, differing from the more extensive patterns reported previously. We suggest a possible postzygotic mutation hypothesis for this unique segmental distribution, addressing both the possibility of a genomic mosaicism and loss of heterozygosity.

Effect of pre-instruction on anxiety levels of patients undergoing magnetic resonance imaging examination.

This study investigated differences in anxiety level of patients who received instruction prior to magnetic resonance imaging (MRI) compared to a control group that did not. Thus, 60 patients were randomly assigned to two groups. Patients in the study group received instructions designed by the researcher plus the routine hospital instructions, while the control group received the routine hospital instructions only. The State--Trait Anxiety Inventory was administered to both groups before and after MRI examination. Patients who received the designed instructions reported significantly lower levels of anxiety than the controls. The findings also indicated that 60% of the total sample used prayer to reduce anxiety. The study emphasizes the need for detailed information about the procedure and training in relaxation techniques.

Effect of pre-instruction on anxiety levels of patients undergoing magnetic resonance imaging examination

This study investigated differences in anxiety level of patients who received instruction prior to magnetic resonance imaging [MRI] compared to a control group that did not. Thus, 60 patients were randomly assigned to two groups. Patients in the study group received instructions designed by the researcher plus the routine hospital instructions, while the control group received the routine hospital instructions only. The State-Trait Anxiety Inventory was administered to both groups before and after MRI examination. Patients who received the designed instructions reported significantly lower levels of anxiety than the controls. The findings also indicated that 60% of the total sample used prayer to reduce anxiety. The study emphasizes the need for detailed information about the procedure and training in relaxation techniques

Long-term outcomes of therapeutic pelvic lymphadenectomy for stage I endometrial adenocarcinoma.

OBJECTIVE: The treatment of patients with stage I endometrial adenocarcinoma is often shorter and less expensive if total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), and therapeutic lymphadenectomy are used rather than TAH, BSO, pelvic lymph node sampling, and pelvic external beam radiation. We studied whether the survival and morbidity of patients treated with therapeutic lymphadenectomy are equal to or better than with these alternative treatments. METHODS: We reviewed the medical records of patients with stage I endometrial adenocarcinoma who were enrolled in the MetroHealth Medical Center tumor registry between 1970 and 1993 after undergoing full pelvic lymph node dissection, in addition to total abdominal hysterectomy, bilateral salpingo-oophorectomy, and vaginal brachytherapy. The mean number of resected nodes was 33 (median, 31; interquartile range, 19). Patients were followed for 1. 6-20 years (median, 8 years; interquartile range, 5.8 years). Morbidity and survival rates were compared to published series using similar treatment strategies and to those from studies using pelvic external beam radiation and pelvic lymph node sampling rather than lymphadenectomy. RESULTS: Of 192 patients with pathologic stage I (FIGO 1988) endometrial adenocarcinoma, 178 patients had full pelvic lymph node dissection; 159 patients were evaluable. The 15-year overall survival was 98%; 10- and 15- year disease-free survivals were 96 and 94%, respectively. Overall morbidity was 18% (29/159), and moderate-to-severe morbidity was 13% (21/159). Recurrences were seen in 4.4% (7/159) of patients. Grade and myometrial invasion were not significant predictors of disease-free survival after full pelvic lymph node dissection (grade, P = 0.42; stage, P = 0.67). The results compare favorably with those of similar studies and with studies of pelvic external beam radiation. CONCLUSIONS: Primary surgical management with total abdominal hysterectomy, bilateral salpingo-oophorectomy, therapeutic pelvic lymphadenectomy, and vaginal brachytherapy is a viable and possibly preferable option for patients with stage I endometrial adenocarcinoma.

P 53 suppressor gene and cathepsin D expression in correlation with cellular and humoral immunity in cutaneous leishmaniasis.

A total of fifteen clinically and parasitologically proven adult cases of cutaneous leishmaniasis were studied for the demonstration of premalignant factor(s). The levels of antibodies against Leishmania parasite were measured with the indirect haemagglutination test (IHAT) and evaluated with the results of lymphoblast transformation test (LTT), a tumour suppressor gene (P53) and an asportic proteinase enzyme (Cathepsin D). Three patients (females) refused to be biopsied. The results showed a direct correlation between elevation of IHAT in 7/12 patients (Titers 1/128 to 1/512) and elevation of LTT in 7/12 patients (82 to 90%). On the other hand, two males with low (?) seropositive IHAT (1/64) and low LTT (20 & 40%) gave positive P53 antibody and moderate (1) and marked (1) degrees Cathepsin D. So, it is concluded that cutaneous leishmaniasis infection particularly chronic one favours the premalignant changes in the granulomatous lesions.