Kikuchi fujimoto disease: a case report

Kikuchi-Fujimoto hastalığı veya histiyositik nekrotizan lenfadenit (HNL) özellikle ortalama 30 yas civarındaki bayanlarda görülen kendiliğinden sınırlanan, nekrotizan servikal lenfadenopati ile karakterize bir hastalıktır. Ates, titreme, kas ve eklem ağrısı, splenomegali ve deride döküntüleri kliniğe eşlik edebilir. Hastalık bir-üç ay içinde kendiliğinden düzelir.Asya'da daha yaygın olmakla beraber bütün dünyada görülebilir. Yirmi yasında, servikal lenfadenopati ve ateş şikayeti olan, eksizyonel lenf nodu biyopsisinde ve patolojik Değerlendirilmesinde HNL tanısı konulan bir erkek hasta sunuldu. HNL hastalığı benin lenfadenopatinin nadir nedenlerinden biridir. Benign, etyolojisi bilinmeyen bu hastalık yaygın olarak lenfoma yanlış tanısını alır. Kendiliğinden sınırlanan bu klinik tablo benign lenfadenopatilerin ayırıcı tanısında gözardı edilmemelidir.Kikuchi-Fujimoto disease or Histiocytic necrotizing lymphadenitis (HNL) is a self-limited disorder characterized by necrotizing cervical lymphadenopathy in especially women (with a mean age of 30 years). It presents with fever, chills, myalgias, arthralgias, splenomegaly, and skin rashes. The disease usually resolves within 1-3 months. It is most common inAsia but has been described worldwide. We present a 20 years old man with complaints of cervical lymphadenopathy and fever, whom diagnosed as Kikuchi-Fujimoto disease with excisional lymph node biopsy and pathological inspection. HNLdisease is one of the rarest causes of benign lymphadenopathy. This disease, whose etiology is not known, is commonly misdiagnosed as lymphoma. This self-limiting disease should be kept in mind in differential diagnosis of benign lymphadenopathies

Diurnal changes in capecitabine clock-controlled metabolism enzymes are responsible for its pharmacokinetics in male mice

The circadian timing system controls absorption, distribution, metabolism, and elimination processes of drug pharmacokinetics over a 24-h period. Exposure of target tissues to the active form of the drug and cytotoxicity display variations depending on the chronopharmacokinetics. For anticancer drugs with narrow therapeutic ranges and dose-limiting side effects, it is particularly important to know the temporal changes in pharmacokinetics. A previous study indicated that pharmacokinetic profile of capecitabine was different depending on dosing time in rat. However, it is not known how such difference is attributed with respect to diurnal rhythm. Therefore, in this study, we evaluated capecitabine-metabolizing enzymes in a diurnal rhythm-dependent manner. To this end, C57BL/6J male mice were orally treated with 500 mg/kg capecitabine at ZT1, ZT7, ZT13, or ZT19. We then determined pharmacokinetics of capecitabine and its metabolites, 5 '-deoxy-5-fluorocytidine (5 ' DFCR), 5 '-deoxy-5-fluorouridine (5 ' DFUR), 5-fluorouracil (5-FU), in plasma and liver. Results revealed that plasma C-max and AUC(0-6h) (area under the plasma concentration-time curve from 0 to 6 h) values of capecitabine, 5 ' DFUR, and 5-FU were higher during the rest phase (ZT1 and ZT7) than the activity phase (ZT13 and ZT19) (p < 0.05). Similarly, C-max and AUC(0-6h) values of 5 ' DFUR and 5-FU in liver were higher during the rest phase than activity phase (p < 0.05), while there was no significant difference in liver concentrations of capecitabine and 5 ' DFCR. We determined the level of the enzymes responsible for the conversion of capecitabine and its metabolites at each ZT. Results indicated the levels of carboxylesterase 1 and 2, cytidine deaminase, uridine phosphorylase 2, and dihydropyrimidine dehydrogenase (p < 0.05) are being rhythmically regulated and, in turn, attributed different pharmacokinetics profiles of capecitabine and its metabolism. This study highlights the importance of capecitabine administration time to increase the efficacy with minimum adverse effects.Istanbul Universit

Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice

Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced oxaliplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53−/− mice by ~25%. Collectively our data suggest that M47 is a promising molecule to treat forms of cancer depending on the p53 mutation

Synthesis and characterizations of novel thiazolyl-thiadiazole derivatives as telomerase activators

WOS: 000433980300014Pyridine-3/4-thiocarboxamide derivatives were used as starting materials for the synthesis of the target compounds. The pyridine-3/4-thiocarboxamide derivatives were reacted with ethyl 2-chloroacetoacetate in ethanol to give the thiazole derivatives (1, 2). The two ethyl thiazole-carboxylate derivatives (1, 2) thus obtained were treated with sodium hydroxide solution and ethanol and converted to carboxylic acids (3, 4). The carboxylic acid derivatives (3, 4) were reacted with thiosemicarbazide in phosphoroxy trichloride and aminothiadiazole rings (5, 6) were formed. Thus, two thiazolyl-thiadiazole amine derivatives (5, 6) were obtained. These two derivatives (5, 6) were converted into two chloroacetamidothiadiazole derivatives (7, 8) by reaction with chloroacetylchloride over the amino group in the presence of triethylamine in acetone. After all these steps, the starting materials (7, 8) needed to reach the target compounds were obtained. With the two derivatives (7, 8) obtained in this last step, phenol and thiophenol derivatives were reacted in acetone in the presence of potassium carbonate. The target compounds, thiazolyl-thiadiazole derivatives (TDA (1-16)) , are completely unique and their structure has been elucidated by elemental analysis, IR, NMR, and MS spectral data. After all these synthesis steps, telomerase activity studies were performed on the target compounds obtained. For this purpose, a PCR ELISA-based TRAP method was used on the heart of zebrafish. According to the enzyme assay results, derivative TDA (8) has shown an increase of telomerase enzyme activity.Scientific and Technological Research Council of Turkey (TUBITAK) [212T181]The synthesis and characterization of this study were supported by the Scientific and Technological Research Council of Turkey (TUBITAK, Grant Number 212T181)

Identification of novel small molecules targeting core clock proteins to regulate circadian rhythm

© 2021 Elsevier LtdThe circadian rhythms are physiological, biochemical, and behavioral oscillations that cycle every 24 hours to anticipate the daily changes in the external environment. Disruption of the circadian clock in mammals results in increased susceptibility to different types of diseases such as metabolic, mood and sleep disorders and cancer. To this end, different approaches have been taken to find small molecules that have the potential to correct the disrupted circadian clock. In this review, we highlight the recent developments in identifying novel molecules that regulate the activities of the core clock proteins. Finally, we discuss virtual screening-based methods using the crystal structures of core clock proteins for the discovery of small molecules that regulate the circadian rhythm

The effects of some imidazopyrazine derivatives on telomerase inhibition, mtDNA damage and mtDNA copy number

Imidazopyrazine derivatives have been studied for their curative effects on some diseases like cancer and neurological problems; also, some of these molecules have been patented. Primary human cells exhibit limited replicative potential but the cancer cells divided unlimitedly with passage in culture. This immortality is mainly a result of telomerase activity. We investigated the possible telomerase inhibitor effect and possible mtDNA damage action of five imidazopyrazine derivatives. Telomerase activities were measured by the PCR-ELISA based TRAP method and mtDNA damage assays were achieved by quantitative PCR. We used zebrafish as a model organism for our research. In the application of 6-(4-Metylphenyl-8-(4-chlorophenyl)imidazo[1,2-a]pyrazine (C19H14N3Cl), it was determined that this compound inhibit telomerase activities to a statistically significant degree. The obtained results from molecular docking studies also supported the experimental results. Accordingly, this compound has the probability to be used as an anti-cancer agent after detailed studies.Firat University Scientific Research Projects Management Unit: 0305-NAP-16, 0214-YL-1