Dynamics of excited state proton transfer in nitro substituted 10-hydroxybenzo[h]quinolines.

The ground state tautomerism and excited state intramolecular proton transfer (ESIPT) of 10-hydroxybenzo[h]quinoline (HBQ) and its nitro derivatives, 7-nitrobenzo[h]quinolin-10-ol (2) and 7,9-dinitrobenzo[h]quinolin-10-ol (3), have been studied in acetonitrile using steady state as well as time dependent spectroscopy and quantum-chemical calculations. In addition to the enol form absorbance in the range 360-390 nm, the absorption spectra of 2 and 3 exhibit a red shifted band at ∼450 nm. Chemometric data processing, based on individual band decomposition, allowed us to estimate the position of the ground state enol-keto tautomeric equilibrium (ΔG values of 1.03 and 0.62 kcal mol-1 respectively for 2 and 3). The fluorescence stems from the keto form even if the enol form is optically excited as proven by the shape of the excitation spectra indicating that ESIPT takes place. The Stokes shift of the substituted compounds is substantially lower compared to HBQ, which follows from the fact that the substitution occurs in the formal cyclohexa-2,4-dienone moiety and leads to a decrease of the HOMO level of the keto tautomer. The pump-probe experiments show that in the nitro substituted HBQs 2 and 3 ESIPT occurs with a time constant of 0.89 ps and 0.68 ps, respectively. In both cases a mixture of the enol and proton transfer forms is optically excited. The enol form exhibits then the ESIPT and subsequently both fractions take the same relaxation path. We propose that in 2 and 3 the ESIPT path exhibits a potential energy barrier resulting in an incoherent rate governed process while in HBQ the ESIPT proceeds as a ballistic wavepacket motion along a path without significant barriers. The theoretical calculations (M06-2X/TZVP) confirm the existence of a barrier in the ground and excited states as result of the substitution.

Evaluation of the clinical value of the newly identified urine biomarker HIST1H4K for diagnosis and prognosis of prostate cancer in Bulgarian patients.

PURPOSE: Searching for diagnostic and prognostic biomarkers for prostate cancer (PC) is main public health priority. DNA methylation in body fluids is a stable, easily detectable and promising PC biomarker. The major advantages of urine-based assays are their noninvasive nature and the ability to monitor PC with heterogeneous foci. The aim of this study was to determine the diagnostic value of the recently identified candidate PC biomarker HIST1H4K. METHODS: We investigated DNA methylation of HIST1H4K in urine samples from 57 PC patients, 29 controls with benign prostatic hyperplasia (BPH) and 50 young asymptomatic men (YAM) by MethyLight real-time PCR. RESULTS: The frequency of HIST1H4K promoter hypermethylation significantly discriminated PC patients from YAM (AUC =0.763; 95% CI 0.672-0.839; p<0.0001), but did not show any statistical difference between PC patients and BPH controls (AUC=0.513, 95% CI 0.402-0.622; p=0.8255). HIST1H4K could not outperform the prostatic specific antigen (PSA) in our sample (AUC=0.785; 95% CI 0.679-0.870; p<0.0001). Methylation of HIST1H4K showed significant correlation with aging (r=0.5418; p<0.0001), but with no other clinicopathological characteristics. CONCLUSION: The results suggest that the promoter hypermethylation of HIST1H4K is rather due to aging than related to prostate carcinogenesis. To elucidate this observation analysis of larger samples is needed.

Simultaneous bilateral breast carcinoma: Histopathological characteristics and CD44/catenin-cadherin profile.

AIMS: Family history of breast carcinoma, multicentric tumor foci in one breast, and in situ lobular carcinoma increase the risk of bilateral breast cancer (BBC), synchronous or metachronous. Synchronous tumors are designated as simultaneous breast carcinoma if they appear at the same time. The CD44 family and cadherin/catenin immunophenotype of this group of BBCs has not yet been evaluated. The aim of this study was to compare clinicopathological characteristics and immunohistochemical profiles of simultaneous BBC and corresponding lymph node metastases in eight patients. METHODS AND RESULTS: In toto 15 primary and 9 metastatic tumors were evaluated. The expression of CD44 variant isoforms, beta-catenin, E, P and N-cadherin were evaluated by immunohistochemistry. Rare types of breast carcinoma were frequent in this group of patients. There were 6 pleomorphic lobular, 5 invasive ductal of usual type, 3 atypical medullary carcinomas, 2 mucinous and one invasive micropapillary carcinoma. The expression CD44v6 was most frequent, followed by CD44v3-10, CD44v5, and CD44v3. CD44v4 was generally not expressed. E-cadherin was expressed in 80% primary tumors, 40% expressed N-cadherin, and 66% expressed P-cadherin. CONCLUSIONS: Generally, simultaneous carcinomas had different morphology and different immunophenotype. Each primary tumor was more similar to its corresponding metastatic tumor than to the contralateral primary tumor.

EPIDEMIOLOGICAL REGISTRY OF NEUROENDOCRINE TUMORS IN BULGARIA--A PILOT SURVEY.

The National registry of patients with neuroendocrine tumors (NET) in Bulgaria was established in 2013 as a joint initiative of the Bulgarian Surgical Society and the Institute for Rare Diseases. The register aims to explore the epidemiology of NET in Bulgaria, as well as the different diagnostic and treatment approaches for the disease throughout the country. This the first of its kind retrospective study of NET in the country is covering the period January 2012 - January 2013. A total of 127 patients with NET were identified. At the time of the survey the average age of patients with NET was 58.61 ± 15.59 years. The data show almost equal distribution between the genders with a slight predominance of women. The largest relative part of NET is those of NET located in the gastrointestinal tract (54.10 ± 4.51%), followed by those located in the pancreas (12.30 ± 2.97%) and in the lungs (10.66 ± 2.79%). In 72.44 ± 3.96% of the patients a immunohistochemical diagnosis was performed. The study confirmed the leading role of the surgery method of the NET management. In 65.83 ± 4.33% of the patients a radical removal of the tumor was conducted, while the relative part of the undertaken partial resection was 7.50 ± 2.40%. A statistically significant association between the type of surgical treatment and during the follow-up of patients was found. An update of the information in the register will allow a more precise determining of the distribution and management of NET in Bulgaria.

[Orbital lymphoma].

INTRODUCTION: Orbital lymphomas are neoplasms with increasing incidence in recent years in immunocompromised, as well as immunocompetent patients, which defines their social importance. AIM: To describe and analyze the experience of the University hospital "'Sv. Ivan Rilski" with the treatment of this pathology for the period 1997-2008. MATERIAL AND METHODS: Fourteen patients (8 females, 6 males - 13 primary orbital lymphomas, 1 systemic lymphoma). Mean age at diagnosis was 65.6 years (from 50 to 80 years). In 2/3 of the patients the lesion was localized in left eye, without a case with bilateral orbital involvement. Seven cases the diagnosis was made 6 months from the onset of symptoms, 5 cases - 1 year and 2 cases - more than one year. The most common clinical symptoms were exophthalmus (12 case), tumor or bulging mass of the eyelid - 8, diplopy - 6, decreased visual acuity - 5. Intraconal localization of the tumor was in 6 cases, extraconal - 2. intra-extraconal - 6. The diagnosis was made by neuro-ophthalmologist and precised with the aid of CT and MRI. All the patients were operated on with the following approaches - fronto-orbital - 9 cases, lateral - 3, anterior orbitotomy (without bone resection) - 2 cases. In six cases "'gross total" resection was achieved, in the rest of the cases the resection was partial. On histological examination, a high grade lymphoma was established in 2 cases with primary orbital lymphoma and one case with systemic lymphoma. All other cases were diagnosed as low-grade B-call small lymphocytic non-Hodgkin's lymphoma. Long-term survival (over 5 years) was observed in 4 cases with primary lymphoma, whereas the patient with systemic form of the disease died 10 months after the operation.

Long time stability of purple membranes from Halobacterium halobium.

The fast component of the electrical signal and the light absorption signals at different resolution times (at lambda = 408 nm) in an untreated purple membrane suspension were measured in order to study the stability of purple membrane fragments. It has been established that there is no change in the rate constants of L----M and M----O transitions of the photocycle in either the electrical or the light absorption signals of purple membrane suspension kept at 4 degrees C for up to 40 days. Moreover, also the amplitudes of the I (negative) and II (positive) components of the electrical signal remained unchanged during this period.

Clinical study of the effect of the preparation DEODAN on leukopenia, induced by cytostatics.

The aim of the study is to establish the effect of the preparation DEODAN on leukopenia induced by chemotherapeutics in oncological patients. DEODAN is an oral preparation, obtained from lyzozyme lysates of Lactobacillus bulgaricus strain "I. Bogdanov patent strain tumoronecroticance B-51" ATCC 21815, called shortly LB51. In the study there are included two groups of patients--from National Oncological Centre, Sofia, the other from Clinic of Medicine, Bertha Academic Hospital, Clinics of Duisburg, Duisburg. All the patients, (78) have undergone combined chemotherapy. In all patients, leukopenia has been established in moderate and medium levels. The scheme of the application of DEODAN has been 3 g, three times a day before meals, from the first day of establishing the disturbances of the haemopoesis. The treatment lasted until the restoration of the haematological values. Only DEODAN was applied. The results obtained show that the recovery of the WBC count (values above 3000) took place in all of the patients between days 3 and 5. None of the patients displayed any infectious or febrile complications, as a result of the applied chemotherapy and the treatment with the preparation. DEODAN also improves the general condition of the patients.