Design and synthesis of phenoxy methyl-oxadiazole compounds against Alzheimer's disease.

This study examines the synthesis and evaluation of 11 newly developed compounds as potential anti-Alzheimer's agents that occur via cholinesterase and ß-secretase inhibition. The compounds were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the modified Ellman method. The results showed that several compounds exhibited significant inhibition of AChE, particularly compounds 6d, 7a, and 7e, which demonstrated high inhibitory activity at lower concentrations, with IC50 values of 0.120, 0.039, and 0.063 µM, respectively. However, the compounds showed limited effectiveness against BChE, with only a few compounds exhibiting moderate inhibition. Compound 7e showed an inhibitory effect against BACE-1 close to that of the standard drug. Structural analysis revealed that the compounds with substituted benzothiazole and thiazole moieties exhibited the most promising inhibitory activity. This study provides valuable insights into the potential of these synthesized derivatives as a treatment against Alzheimer's disease. Moreover, the structure, stability, and properties of the active compounds were further investigated using density functional theory calculations. As a final note, the utilization of molecular docking and molecular dynamics simulation studies allowed us to elucidate the action mechanism of the active compounds and gain insights into the structure-activity relationship against AChE and ß-secretase proteins. These computational techniques provide valuable information on the binding modes, interactions with target enzymes, dynamic behavior, and conformational changes of the compounds, enabling a comprehensive understanding of their biological activity.

An Innovative Study Focused on Reducing Unnecessary Oxygen Exposure in Pediatric Patients.

PURPOSE: In the perioperative period, fractional-inspired oxygen is used at values up to 80% to stay within the safe range, even for a short time. A clear value for the safe range has not been specified, and therefore, clinicians prefer a high oxygen value. This study aims to reduce unnecessary oxygen exposure in pediatrice patients and to provide the optimum fractional inspired oxygen value. DESIGN: The study was designed as a prospective randomized controlled study, including 139 patients aged 1 to 8 years without comorbidity. METHODS: Three groups were formed by adjusting the fractional inspired oxygen to 30%, 50%, or 80% intraoperatively. In the intraoperative period, a strict inspired oxygen protocol (hypoxemia threshold was SpO2 < 90) and oxygen reserve index, fractional expired oxygen value, and peripheral oxygen saturation were used to maintain the balance of hypoxemia and hyperoxemia. FINDINGS: One hundred and nine children were included. The mean oxygen reserve index was significantly lower in the 30% group than in the other groups (0.09 ± 0.05, P < .0001). The mean arterial pressure in the 30% group was significantly lower than the 80% group but within the normal range (78 ± 6 mmHg, P < .003). There was no significant difference between the groups regarding delirium and pain in the recovery unit. CONCLUSIONS: Due to the known and unknown harmful effects of unnecessary oxygen exposure, it may be time to use optimal oxygen and to fear unnecessary oxygen, not less oxygen. As the next step, we think studies should be conducted with patient groups with lower oxygen concentrations (eg, %21 vs %24 vs %30), more patients, and arterial blood gas monitoring.

Gender-based cytomorphometric analysis of buccal exfoliated cells in a South Indian population.

OBJECTIVE: To assess differences based on gender in nuclear area (NA), cytoplasmic area (CA), and nuclear-cytoplasmic ratio (N:C ratio) values for clinically normal buccal smears in apparently healthy subjects of a South Indian population, thereby providing definitive baseline cytomorphometric measurements for the South Indian population. METHODS: Buccal smears were collected from 60 healthy subjects (30 males and 30 females) of a South Indian population above 18 years in age. Values of the NA and CA were measured, and the N:C ratio calculated, using ImageJ software. Statistical analysis of the data with independent t tests and 95% confidence intervals was done using SPSS version 21 (significance set at P < 0.05). RESULTS: The results showed that there were significant differences in the NA, CA, and N:C values between males and females irrespective of age (P = 0.01). CONCLUSION: Definitive gender-specific baseline cytomorphometric data can be established using exfoliative cytology for the South Indian population, and this may be helpful in deciphering the occurrence of oral pre-malignant diseases and oral squamous cell carcinoma in this population, as the incidence of these conditions varies with gender and different ethnic groups.

The global incidence of bullous pemphigoid: a systematic review and meta-analysis.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disorder that mainly affects older people. Although the disease is associated with considerable morbidity and mortality, the burden of disease worldwide is unclear. OBJECTIVES: The study aim is to pool the global incidence of BP and determine whether this varies according to geographic area, age group, setting and study quality. METHODS: Ovid MEDLINE, Ovid Embase and grey literature were systematically searched on 7 April 2020. Two reviewers independently screened, extracted data and appraised each study's quality using the Joanna Briggs Institute critical appraisal tool. Two domains, indicative of selection and survey bias, were used to identify high-quality studies. The cumulative incidence was standardized to 1 year and pooled in a random-effects meta-analysis. Subgroup and sensitivity analyses were conducted. RESULTS: Twenty-seven studies were identified, of which 23 provided cumulative incidence and four provided incidence rates. The cumulative incidence of BP was 8·2 [95% confidence interval (CI) 4·8-13.7] per million people whereas the incidence rate was 34·2 (95% CI 19·2-60·7) per million person-years. Of the continents that contributed more than one study, the cumulative incidence was 10·3 (95% CI 5·8-18·2) and 5·6 (95% CI 3·5-9·0) per million people in Europe and Asia, respectively. The incidence was highest in studies including adults only (n = 2), in population-based studies (n = 9) and in more recent years. The cumulative incidence was higher (13·3 per million people, 95% CI 6·0-29·5) when restricting the analysis to higher-quality studies (n = 11). High heterogeneity (I2 > 82%) was observed across all pooled estimates. CONCLUSIONS: The incidence of BP varies globally, is generally low but appears to be increasing over time. The burden of disease is likely to be underestimated.

Synthesis, anticholinesterase activity, molecular docking, and molecular dynamic simulation studies of 1,3,4-oxadiazole derivatives.

Two new series of 1,3,4-oxadiazoles bearing pyridine and thiazole heterocycles (4a-h and 5a-h) were synthesized (2,5-disubstituted-1,3,4-oxadiazoles). The structures of these newly synthesized compounds were confirmed by 1 H nuclear magnetic resonance (NMR), 13 C NMR, high-resolution mass spectrometric and Fourier transform infrared spectroscopic methods. All these compounds were evaluated for their enzyme inhibitory activities against two cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). From the studies, we identified compounds 4a, 4h, 5a, 5d, and 5e as selective AChE inhibitors, with IC50 values ranging from 0.023 to 0.037 µM. Furthermore, docking studies of these compounds were performed at the active sites of their target enzymes. The molecular docking study showed that 5e possessed an ideal docking pose with interactions inside AChE.

Design, synthesis, biological activity, molecular docking, and molecular dynamics of novel benzimidazole derivatives as potential AChE/MAO-B dual inhibitors.

To develop new acetylcholinesterase (AChE)-monoamine oxidase-B (MAO-B) dual inhibitors against Alzheimer's disease, the benzimidazole ring, which has a propargyl side chain with previously proven selective MAO-B inhibitory activity, was used as the main structure. Moreover, like donepezil, it was thought that the enzyme AChE would provide π-π interactions with the peripheral anionic side in this structure. Piperazine derivatives were chosen for the cationic active site. The synthesis of the compounds was carried out in five steps. The structures of the compounds were determined using 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, and high-resolution mass spectrometry spectroscopic methods. First, the in vitro AChE, butyrylcholinesterase (BChE), MAO-A, and MAO-B inhibitory potentials of the obtained compounds were investigated. As a result of activity tests, compounds 5b, 5e, 5g, and 5h showed inhibitory activity against AChE; compounds 5e and 5g showed inhibitory activity against MAO-B. None of the compounds showed inhibitory activity against BChE or MAO-A. Compounds 5e and 5g showed dual inhibition. Among these compounds, compound 5g had inhibition potential similar to that of donepezil and selegiline. For compound 5g, further kinetic studies and Aß-plaque inhibitory potentials were investigated using in vitro methods. Molecular docking studies were performed using both AChE and hMAO-B crystals to elucidate the compound's interactions with the enzyme active site. The binding modes of the compound on AChE were fully elucidated by molecular dynamics studies.

Design and synthesis of novel chalcone derivatives and evaluation of their inhibitory activities against acetylcholinesterase.

According to the cholinergic hypothesis, an increase in the acetylcholine level in Alzheimer's disease patients relatively slows down the symptoms of the disease. The most commonly used drug, donepezil, is a cholinesterase inhibitor. In this study, 12 new chalcones (2a-l) were designed and synthesized. In biological activity studies, the acetylcholinesterase (AChE) and butyrylcholinesterase inhibitory potentials of all compounds were evaluated using the in vitro Ellman method. The biological evaluation showed that compounds 2d, 2f, 2j, and 2l displayed significant activity against AChE. The compounds 2d, 2f, 2j, and 2l displayed IC50 values of 0.042, 0.024, 0.053, and 0.033 µM against AChE, respectively. The reference drug donepezil (IC50 = 0.021 µM) also displayed significant inhibition of AChE. The inhibitory activities of these compounds for ß-amyloid plaque aggregation were investigated. The enzyme kinetic study was performed to observe the effect of the most active compound 2f on the substrate-enzyme relationship, and a mixed-type inhibition of AchE was determined. Further, docking simulation also revealed that these compounds (2d, 2f, 2j, and 2l) interacted with the enzyme active site in a similar manner to donepezil. The most active derivative, compound 2f, interacted with the amino acids Trp286, Phe295, Tyr341, Trp86, and Glu202.

Design, synthesis, biological evaluation, and docking studies of some novel chalcones as selective COX-2 inhibitors.

A new series of chalcones (1-9) possessing an SO2 CH3 COX-2 pharmacophore at the para position of the C-1 phenyl ring was synthesized via the Claisen-Schmidt condensation reaction and examined for their inhibition potential against cyclooxygenase (COX) enzymes. Their structures were elucidated by infrared, 1 H NMR (nuclear magnetic resonance), 13 C NMR, and high-resolution mass spectroscopic methods. Enzyme inhibition studies revealed that most of the compounds showed a moderate-to-strong inhibitory activity (IC50 = 0.18-0.34 µM) against the COX-2 enzyme as compared with celecoxib (IC50 = 0.12 µM), ibuprofen (IC50 = 5.33 µM), and nimesulide (IC50 = 1.68 µM). Among these compounds, 1-[4-(methylsulfonyl)phenyl]-3-(2,3-dichlorophenyl)prop-2-en-1-one (5), 1-[4-(methylsulfonyl)phenyl]-3-(2,4-dichlorophenyl)prop-2-en-1-one (6), and 1-[4-(methylsulfonyl)phenyl]-3-(2-chloro-6-fluorophenyl)prop-2-en-1-one (8) became prominent with IC50 values of 0.21, 0.19, and 0.18 µM, respectively. According to molecular docking studies of the most effective compounds, it was found that the compounds interact with amino acids that are important in COX-2 selectivity, such as Arg499 and Phe504.

Synthesis and docking study of benzimidazole-triazolothiadiazine hybrids as aromatase inhibitors.

Aromatase is involved in the biosynthesis of estrogen and thus is a critical target for breast cancer. In this study, to identify new aromatase enzyme inhibitors, seven 3-[4-(5-methyl-1H-benzo[d]imidazol-2-yl)phenyl]-6-(substituted phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives were synthesized. First, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the inhibitory activity of the synthesized compounds on the MCF-7 cell line. The aromatase inhibitory activity was determined for the active compounds 5b, 5c, 5e, and 5g on the MCF-7 cell line. Compound 5g showed significant aromatase inhibitory activity (IC50 = 0.037 ± 0.001 µM). Interestingly, this compound, which bears a difluoro substituent at positions 2 and 4 of the phenyl ring, displayed the most potent aromatase inhibitory activity without significant cytotoxicity to a normal healthy cell line (NIH3T3). Furthermore, the interactions between the best active compounds and the active site of the enzyme were analyzed through a docking study. The results of this study determined that benzimidazole-triazolothiadiazine derivatives are promising compounds that should be further developed as a novel class of aromatase inhibitors.

Design, synthesis, in vitro and in silico evaluation of new pyrrole derivatives as monoamine oxidase inhibitors.

In an effort to develop potent monoamine oxidase (MAO) inhibitors, new pyrrole derivatives were obtained via the selective reduction of the CC bonds of 1-(1-methyl-1H-pyrrol-2-yl)-3-[5-(aryl)furan-2-yl]prop-2-en-1-ones through palladium catalyzed hydrogenation in ethanol. The synthesized compounds were screened for their inhibitory effects on MAO-A and MAO-B by an in vitro fluorometric method. The selectivity index (SI) value was given as the ratio of IC50 (MAO-A)/IC50 (MAO-B) for each compound. 3-(5-(4-Chlorophenyl)furan-2-yl)-1-(1-methyl-1H-pyrrol-2-yl)propan-1-one (6) was identified as the most selective MAO-A inhibitor in this series, with an IC50 value of 0.162 µM and a SI value of 0.002. Kinetic studies were also carried out to assess the nature of MAO-A inhibition by compound 6. According to Lineweaver-Burk plots, compound 6 was found to be a competitive MAO-A inhibitor and the Ki value of compound 6 was determined as 0.1221 µM. Docking studies were performed for compound 6 and clorgyline using the human MAO-A crystal structure (PDB ID: 2Z5Y). The docking results showed that compound 6 presented similar interactions as clorgyline in the active center cavity of the enzyme. Molinspiration software was used to determine the physicochemical parameters of all compounds for an evaluation of their compliance to Lipinski's rule of five. Compound 6 did not violate Lipinski's rule, making it a potential orally bioavailable therapeutic agent.

Influence of endophytic root bacteria on the growth, cadmium tolerance and uptake of switchgrass (Panicum virgatum L.).

AIMS: This study aimed to evaluate the effect of five cadmium-tolerant endophytic plant growth-promoting bacteria (PGPB) strains on the biomass and cadmium tolerance, and accumulation of the bioenergy plant switchgrass (Panicum virgatum L.) under cadmium (Cd)-contaminated conditions. METHODS AND RESULTS: Five bacterial strains (Bj05, Le14, Ps14, So02 and Bo03) that could tolerate up to 2000 µmol l-1 CdCl2 with a high Cd-binding capacity were isolated from plants grown in Cd-contaminated soil. These strains could promote the growth of switchgrass in the presence of 20 µmol l-1 CdCl2 . Under Cd stress, both the root and shoot length and biomass in two switchgrass cultivars, Alamo and Cave-in-Rock (CIR), increased significantly after treatment with PGPB (P ˂ 0·05). Of the five PGPB strains, Bj05 and Le14 most effectively alleviated the Cd-induced growth inhibition of Alamo plants. Interestingly, the five PGPB strains increased Cd tolerance and decreased the accumulation and translocation factor (TF) of Cd in switchgrass when grown in the presence of 20 µmol l-1 CdCl2 . The Cd concentrations in roots and shoots of Alamo and CIR plants were significantly reduced (P Ë‚ 0·05) compared with noninoculated plants. By 16S rRNA sequencing, these PGPB strains were classified as Pseudomonas putida Bj05, Pseudomonas fluorescens Ps14, and Enterobacter spp. Le14, So02 and Bo03. CONCLUSION: Inoculation with PGPB protects plants from the inhibitory effects of Cd, improves plant growth and decreases Cd concentration. These observations suggest that these strains could be used to promote growth and lower the bioavailability of Cd in switchgrass. SIGNIFICANCE AND IMPACT OF THE STUDY: These strains are potential candidates for the development of low Cd-accumulating switchgrass, particularly in areas of Cd contamination and pollution, and could be used efficiently for the bioremediation of contaminated soil.

Diagnosis of Dermatophytosis by Conventional Methods and Comparatative analysis of Sabouraud Dextrose Agar and Dermatophyte Test Medium for Isolation of Dermatophytes.

Dermatophytosis is a fungal disease which ranked as one of the most common cutaneous condition in all over the world. The aim of this cross sectional observational study is to identify the etiological agent of dermatophytosis and comparison of Sabouraud dextrose agar (SDA) and Dermatophyte test medium (DTM) for the primary isolation of dermatophytes among the clinically suspected cases of dermatophytosis from the outpatient Department of Dermatology and Venereology, Mymensingh Medical College Hospital from July 2013 to December 2015. Two hundred thirty clinically suspected cases of dermatophytosis were subjected in this study. Sixty three cases (27.4%) were positive for fungus in direct microscopy while 53(23%) were culture positive. Trichophyton rubrum (83%) was found common etiological dermatophyte species followed by Trichophyton mentagrophytes 5(9.4%) and Epidermophyton floccosum 4(7.5%). There was no statistically significant difference between the SDA and DTM (p<0.01) in primary isolation of dermatophytes.

Role of Serum Follicle Stimulating Hormone, Luteinizing Hormone, Testosterone and Prolactin Levels in Azoospermic Male Partner of Subfertile Couple.

This cross sectional study was carried out in the Infertility Unit, Department of Obstetrics and Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from January 2011 and June 2013. Eighty one (81) consecutive azoospermic male partner of married couple, aged 20-50 years with at least two years of subfertility and no known endocrinopathy and ejaculatory dysfunction were included in this study to find out their abnormal hormonal pattern. None of them had received any form of treatment within the last 3 months prior to hormonal evaluation. Men with hypertension, recent fever, chemo or radiation exposure were excluded from the study. Eight weeks interval two semen analyses were done in the Andrology Laboratory of above department following standard WHO guideline, 2004. Using standard ELISA technique, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and prolactin were measured/assayed/estimated. The results of this study demonstrated that 40 (49.4%) men had normal endocrine pattern against 51 (50.6%) with endocrinopathy. The former may be related to obstructive azoospermia, which needs further analyses. Both the increased FSH (>11.1mIU/ml) and LH (>7.6mIU/ml) were observed in 25 (30.9%) men, only elevated FSH (>11.1mIU/ml) in 9(11.1%), and only elevated LH (>7.6mIU/ml) in 7(8.6%). Low testosterone level (<270ng/dl) was observed in 11(13.6%), low TSH (<0.4µIU/ml) in 1(1.2%) and low prolactin (<2.5ng/dl) in 5(6.2%).

Emergence of CTX-M-15 producing E. coli O25b-ST131 clone in a tertiary care hospital of Bangladesh.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL) producing uropathogens has become prevalent worldwide. E. coli O25b-ST131 clone, associated with blaCTX-M-15, has been reported from many parts of the world and is frequently associated with multidrug resistance. Thus far, there are no reports about this clone in Bangladesh. The objective of this study was to investigate ESBL producing uropathogens and to survey the prevalence of E. coli O25b-ST131 clone among ESBL positive E. coli isolates. METHODS: From symptomatic urinary tract infection cases, a total of 800 urine samples were collected. Bacterial identification and antimicrobial susceptibility testing was performed using established methods. Screening of ESBL producers was done using the disk diffusion method. Screening positive isolates were phenotypically confirmed by double disk synergy (DDS) test. Genes encoding ESBLs (blaCTX-M-15, blaOXA-1) were identified both by PCR and DNA sequencing. Phenotypic positive ESBL producers were also studied by PCR for existence of class 1 integron. Subsequently, O25b-ST131 clone was identified by allele specific PCR. RESULTS: Of 138 gram-negative uropathogens, 45 (32.6%) were positive for ESBLs. ESBL producers showed high frequency of antimicrobial resistance except imipenem. Among 45 ESBL producers, 36 (80%) produced blaCTX-M-15, 18 (40%) produced blaOXA-1. Fifteen (33.3%) strains simultaneously produced both blaOXA-1 and blaCTX-M-15. Class 1 integron was present in 30 (66.7%) isolates. Of the 31 blaCTX-M-15 positive E. coli, 22 (71%) were positive for E. coli O25b-ST131 clone and all (100%) belonged to B2 phylogenetic group. CONCLUSION: Rising antimicrobial resistance among uropathogens, and especially the emergence of blaCTX-M-15 positive E. coli O25b-ST131 clone in Bangladesh has provided urgency to the development of novel preventive and therapeutic strategies.

Preoperative neutrophil:lymphocyte and platelet:lymphocyte ratios predict endometrial cancer survival.

BACKGROUND: Variations in systemic inflammatory response biomarker levels have been associated with adverse clinical outcome in various malignancies. This study determined the prognostic significance of preoperative neutrophil:lymphocyte (NLR), platelet:lymphocyte (PLR) and monocyte:lymphocyte (MLR) ratios in endometrial cancer. METHODS: Clinicopathological and 5-year follow-up data were obtained for a retrospective series of surgically treated endometrial cancer patients (n=605). Prognostic significance was determined for overall (OS) and cancer-specific survival (CSS) using Cox proportional hazards models and Kaplan-Meier analysis. Receiver-operator characteristic and log-rank functions were used to optimise cut-offs. NLR, PLR and MLR associations with clinicopathological variables were determined using non-parametric tests. RESULTS: Applying cut-offs of ⩾2.4 (NLR), ⩾240 (PLR) and ⩾0.19 (MLR), NLR and PLR (but not MLR) had independent prognostic significance. Combining NLR and PLR scores stratified patients into low (NLR-low and PLR-low), intermediate (NLR-high or PLR-high) and high risk (NLR-high and PLR-high) groups: multivariable hazard ratio (HR) 2.51; P<0.001 (OS); HR 2.26; P<0.01 (CSS) for high vs low risk patients. Increased NLR and PLR were most strongly associated with advanced stage (P<0.001), whereas increased MLR was strongly associated with older age (P<0.001). CONCLUSION: Both NLR and PLR are independent prognostic indicators for endometrial cancer, which can be combined to provide additional patient stratification.

Quality and quantity of infertility care in Bangladesh.

Infertility is an important health issue which has been neglected in the developing countries. First test-tube babies (triplet) in Bangladesh were born on 30th May, 2001. Although there is no tertiary level infertility center in the public sector, several private centers have come up with the facilities. The objective of the study was to find i) the quality and quantity of infertility care in Bangladesh and ii) the cause of infertility in the attending patients iii) the treatment seeking behaviors iv) and the reasons for not taking treatment among the attending patients. There are now 10 tertiary level Infertility centers in Bangladesh. The information was collected in a preformed datasheet about the facilities and the profile of the patients and the treatment seeking behavior of the attending patients. Out of the ten centers two centers refused to respond and did not disclose their data. Around 16700 new patients are enrolled in a year in the responsive clinics. Five percent (5%) of the patients underwent ART, 7% of the patients gave only one visit, 84% of the patients completed their evaluation, 76% of the patients took treatment. Causes of infertility in the patients taking treatment were male factor in 36.4%, bilateral tubal block in 20.2%, PCOS and anovulation in 31.7%, endometriosis in 19.6%, unexplained in 10.95, combined in 3.5%, ovarian failure in 1.4%, testicular failure in 0.33%, congenital anomaly in 0.3%. The main reason for not taking treatment was financial constrainment. The quality and quantity of infertility care is dependent on the available resources and on the use of the resources by the patients. In developing countries the resources are merging and confined to specified areas which cannot meet the demand of their population. The study gives us the idea of the need and the demand of the services in the country.

Pregnancy outcome following myomectomy.

In developing countries, abdominal myomectomy is still a modality of treatment for large and symptomatic uterine fibroid in women who wish to retain their fertility and preserve uterus. In order to assess the outcome of pregnancies after myomectomy, a prospective observational study was carried out in the Department of Obstetrics and Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from July 1999 and June 2011. Study included 40 married women of reproductive age, suffering either from primary or secondary subfertility, and who had uterine fibroid and strongly wished to conceive shortly after myomectomy using microsurgical procedure with no existence of other male and female subfertility factor. These women were followed up at 3, 6, 12 and 24 month intervals over telephone and outdoor visits. Data were recorded on preformed questionnaires. Post myomectomy hysterosalpingography was done at about 16 weeks after myomectomy. Patients were advised to try for pregnancy after 16 weeks of operation. Maximum number of women belonged to age group 31-35 years (n=14, 35%); primary subfertility was 67.5% and secondary 32.5%; in maximum number of cases duration of subfertility was 2-5 years (n=22, 55%); type of fibroid were solitary (52.5%) and multiple (47.5%); type of myoma were intramural (75%), submucous (2.5%) and combined (22.5%); location of myoma were fundal (5%), anterior wall (25%), posterior wall (20%) and combined (50%); diameter of removed myoma were <5cm (2.5%), 5-8cm (67.5%), >8-10(20%) and >10cm (10%); uterine size before myomectomy were (in weeks) <12(22.5%), 12-14 (27.5%), 15-20 (32.5%), 21-25 (15%) and >25 (2.5%). Hysterosalpingography was done in 16(40%) cases, and the findings were both tube patent (62.5%), unilateral tubal block (31.2%) and bilateral tubal block (6.2%). Menorrhagia after myomectomy was present only in 5% cases. After uterine myomectomy, 14(35%) women conceived, common time interval between myomectomy and conception was 1-2 years (42.9%), conception was spontaneous in 71.4%. Out of 14 who conceived after myomectomy 12(85.7%) delivered live babies by LUCS, and most of the babies weighed >3kg (58.3%).

Proton transfer reactions of 4'-chloro substituted 3-hydroxyflavone in solvents and aqueous micelle solutions.

Flavonol 4'-chloro,3-hydroxyflavone (Cl-3HF) has been investigated in solvents of varying polarity and hydrogen-bonding capacity as well as in aqueous micelle solutions. Quantum chemical calculations indicate that although the Cl-atom at the 4'-position of the 2-phenyl ring weakly perturbs the electron distribution of the parent 3-hydroxyflavone, the nuclear framework remains largely intact, and excited state intra-molecular proton-transfer (ESIPT) is feasible. The ESIPT process in both polar solvents and micelles was found to be fast and irreversible, with remarkably long time-constants of several tens of picoseconds. This dramatic inhibition of the ESIPT rate (which is intrinsically a sub-picosecond event) could be rationalized in terms of the emergence of complexes between the solvent and the enol form of Cl-3HF, whose dynamics is coupled to the relatively slow dynamics of inter-molecular hydrogen bonds. In the micelle solutions, spectroscopic data establish that the guest Cl-3HF molecules localized almost exclusively at the polar exterior shell, where they experienced a nearly uniform local environment similar to that in moderately polar solvents. Thus, the Cl-3HF molecules tend to avoid the non-polar core of the micelles, in spite of being strongly hydrophobic themselves. This apparently unusual observation is explained by the formation of inter-molecularly hydrogen-bonded complexes between the guest Cl-3HF and the water molecules tethered to the polar shells of the micelles.

[Neuroendocrine neoplasms of the distal jejunum and ileum]. / Neuroendokrine Neoplasien des distalen Jejunums und Ileums.

Neuroendocrine neoplasms (NEN) of the distal jejunum and ileum derive from serotonin-producing enterochromaffin (EC) cells. Due to their low proliferation rate and their infiltrative growth, they are often discovered at an advanced disease stage when metastasis has already occurred. The biology of these tumours is different from other NEN of the digestive tract. In order to standardise and improve diagnosis and therapy, the guidelines for the diagnosis and clinical management of jejuno-ileal NEN as well as for the management of patients with liver and other distant metastases from NEN were revised by the European Neuroendocrine Tumour Society (ENETS) in 2012. This review focuses on aspects relevant for surgical pathology.

[Gastric and duodenal perforations: what is the role of laparoscopic surgery?]. / Magen- und Duodenalperforation: Welchen Stellenwert hat die laparoskopische Chirurgie?

INTRODUCTION: The gastric and duodenal perforations are a life-threatening complication of peptic ulcer disease with the indication for immediate surgical intervention. To which extent laparoscopy is a suitable method in an acute situation was examined in the present investigation. MATERIALS AND METHODS: The data of all patients within a period of 15 years (01/1996-12/2010) who were operated laparoscopically because of a perforated gastric or duodenal ulcer, were collected prospectively in terms of age, gender, localisation of perforation, diagnostics, symptoms, surgical procedures, intraoperative and postoperative complications and postoperative course, and were analysed retrospectively. RESULTS: During the observation period 45 patients were operated laparoscopically due to gastric or duodenal perforation. The median age at operation was 58 (18-91) years. An NSAID medication was present in 11 (24.4 %) patients. The perforation was juxtapyloric in 12 (26.7 %) patients, postpyloric in 10 (22.2 %) patients, one (2.2 %) patient in each small and greater curvature, in 18 (40.0 %) at the front and in three (6.7 %) patients on the rear wall. In two cases, previous surgical treatment in the upper abdomen was performed. After primary diagnostic laparoscopy, an indication for conversion was seen in 20 (44.4 %) patients. During laparoscopically completed operations simple suturing was done in 18/25 (72.0 %) patients and excision and suturing was performed in 7/25 (37.8 %) patients. After conversion simple suturing was observed in 7/20 (35.0 %) patients, whereas in 10/20 (50.0 %) patients excision and suturing was performed. 3/20 (15.0 %) patients underwent a resective operation. The median operative time was 105 (40-306) minutes and mean hospitalisation 11 (4-66) days. The ICU stay was in median 2 (0-37) days. Major complications were seen in 11 (24.4 %) patients, namely re-laparotomy (n = 7; 15.6 %) and haemorrhage (n = 4; 8.9 %). Minor complications were observed in 8 (17.8 %) of cases. The mortality rate was 11.1 % (n = 5). CONCLUSION: The laparoscopic treatment of gastric and duodenal perforations is a minimally invasive therapeutic option for the definitive treatment of this life-threatening disease. The indication for a laparoscopic approach has to be considered individually and depends to a decisive extent on the experience of the laparoscopic surgeon.