Synthesis and in vitro anti-Toxoplasma gondii activity of a new series of aryloxyacetophenone thiosemicarbazones.

A new series of aryloxyacetophenone thiosemicarbazones 4a-q have been synthesized as anti-Toxoplasma gondii agents. All compounds showed significant inhibitory activity against T. gondii-infected cells (IC50 values 1.09-25.19 µg/mL). The 4-fluorophenoxy derivative (4l) was the most potent compound with the highest selectivity toward host cells (SI = 19), being better than standard drug pyrimethamine. SAR study indicated that the concurrence of proper substituents on both aryl ring of phenoxyacetophenone is important for potency and safety profile. Further in vitro experiments with the representative compounds 4l and 4p revealed that these compounds at the concentration of 5 µg/mL can significantly reduce the viability of T. gondii tachyzoites, as well as their infectivity rate and intracellular proliferation, comparable to those of pyrimethamine.

Design, synthesis and biological evaluation of flexible and rigid analogs of 4H-1,2,4-triazoles bearing 3,4,5-trimethoxyphenyl moiety as new antiproliferative agents.

Several flexible and rigid analogs of 4H-1,2,4-triazoles (compounds 8a-g and 9a-g) bearing trimethoxyphenyl pharmacophoric unit, were designed and synthesized as potential anticancer agents. The in vitro cytotoxic assay indicated that both flexible and rigid analogs (8 and 9, respectively) can potentially inhibit the growth of cancerous cells (A549, MCF7, and SKOV3), with IC50 values less than 5.0 µM. Furthermore, compounds 10a-l as regional isomers of compounds 9 exhibited remarkable cytotoxic activity with IC50 values ranging from 0.30 to 5.0 µM. The rigid analogs 9a, 10h and 10k were significantly more potent than etoposide against MCF7, SKOV3 and A549 cells, respectively. These compounds showed high selectivity towards cancer cells over normal cells, as they had no significant cytotoxicity against L929 cells. In addition, the representative compounds 9a and 10h could inhibit the tubulin polymerization at micro-molar levels. By determining changes in the colchicine-tubulin fluorescence, it was suggested that compound 10h could bind to the tubulin at the colchicine pocket. The molecular docking study further confirmed the inhibitory activity of promising compounds 9a, 10h and 10k on tubulin polymerization through binding to the colchicine-binding site.

New potent antifungal triazole alcohols containing N-benzylpiperazine carbodithioate moiety: Synthesis, in vitro evaluation and in silico study.

A number of 1H-1,2,4-triazole alcohols containing N-(halobenzyl)piperazine carbodithioate moiety have been designed and synthesized as potent antifungal agents. In vitro bioassays against different Candida species including C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis revealed that the N-(4-chlorobenzyl) derivative (6b) with MIC values of 0.063-0.5 µg/mL had the best profile of activity, being 4-32 times more potent than fluconazole. Docking simulation studies confirmed the better fitting of compound 6b in the active site of lanosterol 14α-demethylase (CYP51) enzyme, the main target of azole antifungals. Particularly, the potential of compound 6b against fluconazole-resistant isolates along with its minimal toxicity against human erythrocytes and HepG2 cells make this prototype compound as a good lead for discovery of potent and safe antifungal agents.

Assessing the correlation between trichoscopic features in lichen planopilaris and lichen planopilaris activity index.

BACKGROUND/OBJECTIVES: Videodermoscopy is a valuable tool for the diagnosis of cicatricial alopecias such as lichen planopilaris. Lichen planopilaris activity index is used for evaluating lichen planopilaris severity. Our aim was to examine the utility of videodermoscopy in the assessment of lichen planopilaris severity. METHODS: One hundred and seventeen histopathologically confirmed lichen planopilaris patients under went videodermoscopy. Lichen planopilaris activity index was calculated according to cicatricial alopecia standardised flowchart. Differences and correlations between trichoscopic features, clinical findings and lichen planopilaris activity index were calculated. RESULTS: Most trichoscopic features had statistically significant higher prevalence than similar clinical findings. Targetoid pigment pattern, perifollicular scale and milky-red areas were significantly correlated with lichen planopilaris activity index (P-value < 0.05). There was statistically significant correlation between targetoid pigment pattern and positive anagen pull test (P-value < 0.001). CONCLUSION: Using trichoscopic features in calculating lichen planopilaris activity index with videodermoscope can help in early lichen planopilaris diagnosis and improve post-treatment follow-up.

Mercury and arsenic in green tiger shrimp from the Persian Gulf.

Mercury and arsenic pollution has been recognized as a potential environmental and public health problem for over 40 years. The major source of exposure to mercury and arsenic for humans is the ingestion of sea food. Concentrations of mercury and arsenic in the muscle samples of green tiger shrimp (Penaeus semisulcatus) from the Persian Gulf were determined by cold vapor atomic absorption spectrometry. Concentrations of metals in muscle samples were 49-115 µg kg(-1) for mercury, 115-131 µg kg(-1)for arsenic, with means of 82.7 and 251.6 µg kg(-1), respectively. Statistical analysis showed no significant difference of mercury and arsenic concentration in shrimp muscles between selected stations (Bushehr, Khuzestan, and Hormozgan provinces). No significant difference was found among heavy metal contents of male and female shrimps. The results of this study indicate that the green tiger shrimp from the Persian Gulf have concentrations well below the maximum permissible levels for mercury (500 µg kg(-1)) and arsenic (6000 µg kg(-1)), according to international standards, with no health risk of consumers.

Health risk assessment of mercury and arsenic associated with consumption of fish from the Persian Gulf.

Concentrations of mercury and arsenic in fish from the Persian Gulf were determined by graphite furnace atomic absorption spectrometry. Concentrations of the metals in muscle samples were 0.049-0.402 µg g(-1) for mercury and 0.168-0.479 µg g(-1) for arsenic, with means of 0.133 and 0.312 µg g(-1), respectively. The maximum daily consumption rate (grams per day) and meal consumption limit (meals per month) was calculated to estimate health risks associated with fish consumption. According to the results, the maximum allowable consumption rate varies between 8-56 and 15-96 g/day base on mercury and arsenic content, respectively. The results of this study indicate that the concentration of mercury and arsenic is well below the maximum permissible levels for mercury (0.5 µg g(-1)) and arsenic (6 µg g(-1)) according to international standards.

Epithelioid hemangioma (ALHE) on the tongue of an infant treated with oral corticosteroids: A case report and review of the literature.

Epithelioid hemangioma or angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign vascular lesion presenting as multiple nodules on the head and neck. Surgery had been considered to be the best treatment modality for ALHE. We report the case of a 6-month-old boy with ALHE on his tongue that was treated successfully with oral prednisolone.

A systematic review of the concentration of potentially toxic elements in fish from the Persian Gulf: A health risk assessment study.

Fish as a critical food source is responsible for supplying nearly 20% of the average per capita animal protein for 3.2 billion people worldwide. However, oral exposure to potentially toxic elements (PTE) such as mercury (Hg), cadmium (Cd), lead (Pb), and arsenic (As) through marine fish consumption can cause health risks in consumers. This study aimed to collect information among databases (2000-2020), including ScienceDirect, PubMed, SCOPUS, EMBASE, and Google Scholar, regarding the concentration of PTEs in different types of fish from the Persian Gulf. In this regard, thirty articles containing 266 samples were included in the current systematic review. In addition, the non-carcinogenic risk caused by ingestion of PTEs via consumption of fish was calculated. The average PTE concentrations in fish muscles were presented in the following order: As (0.37 mg/kg ww) > Pb (0.20 mg/kg ww) > Cd (0.17 mg/kg ww) > Hg (0.13 mg/kg ww). However, the mean concentration of PTEs was below the defined level by the World Health Organization, and the findings revealed that the calculated average daily dose (ADD) for Cd and Pb in Iranian children and adult consumers was lower than the reference dose (RfD), whereas the ADD of Hg was higher than the RfD for children consumers. The total target hazard quotient for Iranian and children consumers was >1. The excess lifetime cancer risk values for Pb were safe, unlike those for Cd, which were in an unsafe range (>10-4) for consumers.

Mercury, arsenic, cadmium and lead in lobster (Panulirus homarus) from the Persian Gulf.

Concentrations of four toxic metals including mercury, arsenic, lead and cadmium in lobster (Panulirus homarus) muscles from the Persian Gulf were determined by graphite furnace atomic absorption spectrometry. Heavy metals concentrations in muscle samples were 32-73 µg/kg for mercury, 118-275 µg/kg for arsenic, 379-1120 µg/kg for lead and 101-401 µg/kg for cadmium, with means of 48.7 µg/kg, 184.3 µg/kg, 629.4 µg/kg and 2 50.6 µg/kg, respectively. Most of the heavy metals studied in the edible muscle tissue in P. homarus ranged within the recommended limits for human consumption, except lead, which was found to be above the acceptable level and represents a health risk for consumers.

New thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety as anticancer agents.

A new series of thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety were synthesized as diaryl-heterocylic analogs of combretastatin A-4 with anticancer activity. The cytotoxicity evaluation of synthesized compounds against cancer cell lines (A549, MCF-7 and SKOV3) revealed that most of them had potent cytotoxic activity toward all tested cell lines (IC50s < 10 µg/mL). Among them, 3-(chlorobenzyl) derivatives 5c and 5d showed the best inhibitory effect on MCF-7 cells (IC50 values of 1.14 and 2.41 µg/mL, respectively). Furthermore, the ability of tubulin polymerization inhibition and apoptosis induction were evaluated for the promising compounds 5c and 5d. Results suggested that these compounds remarkably inhibit tubulin polymerization and induce apoptosis resulting in cell death. In vitro studies revealed that these compounds had no significant cytotoxicity against normal cells at the concentrations required for growth inhibition of cancer cells. In vitro biding assay and in silico docking study also confirmed the binding of prototype compound to the colchicine binding site of tubulin.

Serious complication as a result of lip augmentation with vitamin E.

Nowadays lip augmentation with FDA-approved fillers is becoming popular. However, because of financial concerns many patients seek for unregistered materials. Here, we report two cases who use vitamin E for lip augmentation. They experience severe infiltration and discharge less than one month after injection. Biopsy revealed lipogranuloma formation. They were treated with incision and drainage, antibiotic, and corticosteroids. Although these complications are usually difficult to treat, the patients had good clinical response and no recurrence in 5-month follow-up.

ß-Ionone and its analogs as promising anticancer agents.

ß-Ionone is an end-ring analog of ß-carotenoids which widely distributed in fruit and vegetables. Recent studies have demonstrated anti-proliferative, anti-metastatic and apoptosis induction properties of ß-ionone in vitro and in vivo. Also, the studies have focused on investigating the ß-ionone action on different types of malignant cells and the possible mechanisms of action. Moreover, the quest of new synthetic ß-ionone-based compounds possessing anti-proliferative, anti-metastatic and apoptosis induction activities may enable the discovery of compounds which can be used in combination regimes thus overcoming tumor resistance to conventional anticancer agents. These new agents will also be useful for targeting distinct signaling pathways, to activate selectively mechanisms for apoptosis in cancer cells but devoid of undesirable side effects. In this paper, we reviewed the potentialities of ß-ionone and related compounds in cancer prevention and chemotherapy.

Validity of trichoscopy in the diagnosis of primary cicatricial alopecias.

BACKGROUND: There are limited data on the validity of dermatoscopy in primary cicatricial alopecias (PCAs) and its subtypes, including lichen planopilaris and discoid lupus erythematosus. Trichoscopic features of PCAs, their prevalence, and validity were evaluated in this study. METHODS: One hundred patients with PCA underwent dermatoscopy. Biopsy specimens were obtained after the site was marked with a dermatoscope. The control group comprised 100 patients with non-cicatricial alopecia and 100 normal individuals. Finally, the prevalence, sensitivity, and specificity of trichoscopic features were evaluated using SPSS and Stata software. RESULTS: The absence of follicular opening, perifollicular scale, and presence of one scarring pattern or white patch were sensitive and specific patterns in the trichoscopy of PCAs. The presence of tortuous branching vessels and follicular keratotic plugging was 100% specific for a diagnosis of discoid lupus erythematosus. CONCLUSIONS: Some trichoscopic features can help a dermatologist to differentiate between non-cicatricial alopecia and PCA. Moreover, a group of dermatoscopic features can be helpful in the diagnosis of PCA subtypes.

Primary Cutaneous Lymphoma-Associated Pseudoepitheliomatous Hyperplasia Masquerading as Squamous Cell Carcinoma in a Young Adult.

Primary cutaneous anaplastic large cell lymphoma is a T-cell malignancy with atypical CD30 positive lymphocytes. Pseudoepitheliomatous hyperplasia is an uncommon finding in primary cutaneous anaplastic large cell lymphoma, and may mimic squamous cell carcinoma as pseudomalignancy. Careful attention of a pathologist to correct diagnosis of pseudoepitheliomatous hyperplasia and its underlying causes will help physicians to avoid inappropriate management. Here, we present a 22-year-old man referred to our hospital with a solitary nodule persistent on his forearm which was diagnosed as squamous cell carcinoma in the first biopsy. The lesion recurred after two months and histopathologic and immunohistochemistry examination revealed anaplastic large cell lymphoma with florid pseudoepitheliomatous hyperplasia which masquerading as well-differentiated squamous cell carcinoma. Diagnosis of pseudoepitheliomatous hyperplasia must guide the pathologist to search for underlying causes, such as primary cutaneous lymphoma. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and this can result in inappropriate diagnosis and management.

Hoarseness as the Presenting Symptom of Visceral Leishmaniasis with Muco-Cutaneous Lesions: A Case Report.

Herein, a 28-year-old man with hoarseness, skin and oral lesions is presented. At the time of admission, the patient had an erythematous plaque on his chin near his lower lip and an erythematous-violaceous plaque on his palate near the opening of the pharynx and 20 kg weight lost in last one year. The biopsy of his skin lesions by hematoxylin and eosin staining revealed an infiltration of the dermis by lymphoplasma and histiocytic cells with a loose granuloma formation suggestive of leishmaniasis. Biopsy of mucosal lesions revealed Leishman bodies in dermis. PCR was performed on the specimens of skin, bone marrow, mucosa, and saliva, the results were positive. The pathogenic agent was identified as Leishmania major by the nested PCR. Serologic tests including direct agglutination test (DAT) and indirect immunofluorescence test (IFAT) were positive with high titers of anti-L. infantum antibodies (1:102400 versus 1:800, respectively), indicative of visceral involvement. The patient responded to a combination of miltefosine and meglumine antimoniate (Glucantime®). Visceral involvement due to L. major is rarely reported. To the best of our knowledge, probably hoarseness due to L. major has not been previously reported from Iran.

Total serum IgE concentration in patients with psoriasis: a case-control study.

Psoriasis is a chronic relapsing disorder that involves the skin, nails and joints. With regard to the role of the immune system in psoriasis, the current study compared serum IgE concentration in patients with psoriasis with control group. Current case-control study was conducted in Dermatology clinic of Razi hospital, Tehran University of medical sciences, Tehran, Iran in 2012. Fifty-eight patients with psoriasis e referred to the clinic were assigned as patient group and 58 healthy subjects with matched age and sex as a control group. Patient's history, family history and demographic characteristics such as age and sex, duration and severity of disease using PASI, were collected and entered into a form. Consent form was obtained from participants. Serum IgE concentrations of both study groups were measured by electrochemiluminescence assay in the laboratory A total number of 58 patients with psoriasis, mean age of 44.15 (19-76 years) and 58 controls with matched age and sex were studied. Mean average of serum IgE concentration in the control group was 115.13 versus 200/06 concentration in patients group (P=0.16). Serum IgE concentration in 22.4% of patients versus 17.2% in controls was greater than normal concentration (P=0.48). No significant correlation was between serum IgE concentration and disease severity using PASI (P=0.11, r=0.21), neither a significant correlation with disease duration, age and gender. According to the present study, serum IgE concentrations are not greater in patients with psoriasis. IgE concentration is also not associated with the severity of psoriasis based on the PASI score, therefore, the role of IgE in psoriasis can be considered insignificant as some previous studies indicate.

Indeterminate cell histiocytosis: report of a case.

Indeterminate cell histiocytosis is a very rare disorder of histiocytes proliferation. It has both Langerhans and non-Langerhans cell histiocytosis immunophenotypic features. We described a 45-year-old man with a 2 years history of multiple yellow-brown papules and a few red nodules on his trunk and extremities. No internal involvement was detected first and after 8 months. As his lesions were asymptomatic and sparse, he didn't receive any treatment. He will be followed at regular intervals.

Replacement of the methylene of dihydrochalcones with oxygen: synthesis and biological evaluation of 2-phenoxyacetophenones.

With the aim of finding new bioactive compounds, a series of phenoxyacetophenone derivatives 2 were designed and synthesized as oxygen analogs of dihydrochalcones. Also, phenoxyacetophenones were converted to (Z)-oxime derivatives 3 and their geometry were characterized by ¹H-NMR spectroscopy. The in vitro antifungal activity of compounds 2 and 3 was evaluated against Candida albicans, Candida glabrata, Saccharomyces cerevisiae, and Aspergillus niger using micro-dilution method. In general, oxime derivative 3d containing 4-fluorophenoxy moiety showed comparable or more potent antifungal activity (MICs = 15.63-31.25 µg/mL) with respect to the reference drug fluconazole against all tested yeasts. In addition, the antileishmanial activity of title compounds was determined against pormastigote form of Leishmania major. All compounds showed mild growth inhibitory activity against promastigotes. The most active compound was unsubstituted phenoxyacetophenone 2a (IC50 = 80 µg/mL). To anticipate the potential use as drugs, the target compounds were evaluated in their drug-like properties. The in silico values of molecular descriptors for bioactive compounds 2a and 3d revealed that these compounds are within the range set by Lipinski's 'Rule of 5' and show no violation of these rules. Moreover, bioactive compounds 2a and 3d are supposed to be non-mutagenic and non-tumorigenic, with no irritating or reproductive effects.