Utility of thiocarbamoyl moiety in synthesis of some new sulphur containing heterocyclic compounds and evaluation of their antimicrobial activity

The reaction of N,N'-(1,4-phenylene)bis(2-cyanoacetamide) (1) with phenyl isothiocyanate gave thiocarbamoyl derivative 3, which reacted with α-halocarbonyl compounds in a mixture of ethanol:N,N-dimethylformamide in the presence of triethylamineto afford thiazoles 4, 7, 10 and thiophene12 derivatives. While, when the same reaction was refluxed in a mixture of ethanol:N,N-dimethylformamide only afforded the acyclic compounds 5, 6, 8, 9 and 11, which when refluxed in N,N-dimethylformamide in presence of triethylamine gave the corresponding above thiazole and thiophene derivatives. Moreover, the reaction of compound 3 with dihalo compounds afforded cyclic dithio derivatives 13a, 13b and 14. The newly synthesized compounds were characterized by analytical, spectral data and evaluation of their antimicrobial activities of 4, 7, 14 and 15 have a high antimicrobial activity

Studies with aza-heterocyclic N-oxides: Synthesis of some new aromatic N-oxide derivatives

Benzofuroxan derivative (1a) reacts with the cyanoacetanilides (2a-d) to give the benzimidazole derivatives (3a-d). Benzofuroxan (1b) reacts with rhodanine derivatives (4a,b) in presence of sodium ethoxide to give the arylaminobenzoimidazole derivatives (6a,b); while the last reaction afforded the thiazolidinone derivatives (8a,b) and the o-benzoquinone dioxime derivatives (9a,b) when it was repeated in the presence of sodium acetate. Moreover, a series of quinoxalinyl 1,4-di-N-oxide derivatives were prepared starting from quinoxalin-1,4-di-N-oxide derivatives (10a-c). Plausible mechanisms to account for the formation of the products are discussed

Updates in the pathogenesis, diagnosis and management of ectopic varices

Ectopic varices (EcV) comprise large portosystemic venous collaterals located anywhere other than the gastro-oesophageal region. No large series or randomized-controlled trials address this subject, and therefore its management is based on available expertise and facilities, and may require a multidisciplinary team approach. EcV are common findings during endoscopy in portal hypertensive patients and their bleeding accounts for only 1–5% of all variceal bleeding. EcV develop secondary to portal hypertension (PHT), surgical procedures, anomalies in venous outflow, or abdominal vascular thrombosis and may be familial in origin. Bleeding EcV may present with anaemia, shock, haematemesis, melaena or haematochezia and should be considered in patients with PHT and gastrointestinal bleeding or anaemia of obscure origin. EcV may be discovered during panendoscopy, enteroscopy, endoscopic ultrasound, wireless capsule endoscopy, diagnostic angiography, multislice helical computed tomography, magnetic resonance angiography, colour Doppler-flow imaging, laparotomy, laparoscopy and occasionally during autopsy. Patients with suspected EcV bleeding need immediate assessment, resuscitation, haemodynamic stabilization and referral to specialist centres. Management of EcV involves medical, endoscopic, interventional radiological and surgical modalities depending on patients’ condition, site of varices, available expertise and patients’ subsequent management plan

Specific immunoassays confirm association of <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> with type-1 but not type-2 diabetes mellitus

Background Mycobacterium avium subspecies paratuberculosis (MAP) is a versatile pathogen with a broad host range. Its association with type-1 diabetes mellitus (T1DM) has been recently proposed. Rapid identification of infectious agents such as MAP in diabetic patients at the level of clinics might be helpful in deciphering the role of chronic bacterial infection in the development of autoimmune diseases such as T1DM. Methodology/Principal Findings We describe use of an ELISA method to identify live circulating MAP through the detection of a cell envelope protein, MptD by a specific M13 phage – fMptD. We also used another ELISA format to detect immune response to MptD peptide. Both the methods were tested with blood plasma obtained from T1DM, type-2 diabetes (T2DM) patients and non-diabetic controls. Our results demonstrate MptD and fMptD ELISA assays to be accurate and sensitive to detect MAP bacilli in a large fraction (47.3%) of T1DM patients as compared to non-diabetic controls (12.6%) and those with confirmed T2DM (7.7%). Comparative analysis of ELISA assays performed here with 3 other MAP antigen preparations, namely HbHA, Gsd and whole cell MAP lysates confirmed comparable sensitivity of the MptD peptide and the fMptD based ELISA assays. Moreover, we were successful in demonstrating positive bacterial culture in two of the clinical specimen derived from T1DM patients. Conclusions and Significance The MptD peptide/fMptD based ELISA or similar tests could be suggested as rapid and specific field level diagnostic tests for the identification of MAP in diabetic patients and for finding the explanations towards the occurrence of type-1 or type-2 diabetes in the light of an active infectious trigger

Effect of Gastric Fluid Volume on the in Vitro Dissolution and in Vivo Absorption of BCS Class II Drugs: A Case Study with Nifedipine

Nifedipine is a BCS Class II drug used for treatment of hypertension and preterm labor. Large inter-patient variability in nifedipine absorption results in variable exposure among different patients. We conducted in vitro dissolution studies to compare nifedipine dissolution from immediate release (IR) capsules with different volumes of dissolution media. Results from dissolution studies were used to design a crossover study in healthy volunteers to evaluate the effect of coadministered water volume with nifedipine 10 mg IR capsules on nifedipine pharmacokinetics, especially absorption (Cmax, tmax, and AUC0-6). Dissolution studies demonstrated that larger gastric fluid volumes result in enhanced nifedipine dissolution from 10 mg IR cosolvent capsules (73 vs. 17% in 200 and 100 mL simulated gastric fluid, respectively, at 30 min). The pharmacokinetic crossover study in healthy volunteers (N = 6) did not show a significant effect of the water volume administered with the capsule (50 vs. 250 mL) on Cmax, tmax, or AUC0-6 of orally administered nifedipine IR capsules (10 mg). However, administration of large water volumes resulted in lower variability in nifedipine Cmax (47 vs. 70% for 250 and 50 mL, respectively). Administration of large water volumes with nifedipine 10 mg IR cosolvent capsules may reduce inter-individual variability in plasma exposure. Evaluation of similar effects in other BCS Class II drugs is recommended

LC-MS analysis to determine the biodistribution of a polymer coated ilomastat ocular implant

Ilomastat is a matrix metalloproteinase inhibitor (MMPi) that has shown the potential to inhibit scarring (fibrosis) by mediating healing after injury or surgery. A long lasting ocular implantable pharmaceutical formulation of ilomastat is being developed to mediate the healing process to prevent scarring after glaucoma filtration surgery. The ilomastat implant was coated with water permeable and biocompatible phosphoryl choline polymer (PC1059) displayed extended slow release of ilomastat in vitro and in vivo. The ocular distribution of ilomastat from the implant in rabbits at day 30 post surgery was determined by the extraction of ilomastat and its internal standard marimastat from the ocular tissues, plasma, aqueous humour and vitreous fluid followed by capillary-flow liquid chromatography (cap-LC), the column effluent was directed into a triple quadrupole mass spectrometer operating in product scan mode. The lower limits of quantification (LLOQs) were 0.3 pg/μL for ocular fluids and plasma, and 3 pg/mg for ocular tissues. The extraction recoveries were 90-95% for ilomastat and its internal standard from ocular tissues. Ilomastat was found in ocular fluids and tissues at day 30 after surgery. The level of ilomastat was 18 times higher in the aqueous humour than vitreous humour. The concentration ranking of ilomastat in the ocular tissues was sclera > bleb conjunctiva > conjunctiva (rest of the eye) > cornea. Mass spectrometry analysis to confirm the presence of ilomastat in the ocular tissues and fluids at day 30 post-surgery establishes the extended release of ilomastat can be achieved in vivo, which is crucial information for optimisation of the ilomastat coated implant

Evaluation of Antiulcer and Cytotoxic Potential of the Leaf, Flower, and Fruit Extracts of Calotropis procera

Calotropis procera is traditionally used for treating many diseases including ulcers and tumors. It was thus deemed of interest to investigate and compare the antiulcer and cytotoxic activities of C. procera leaf, flower, and fruit extracts in an attempt to verify its traditional uses. Phytochemical studies on the fruits, flowers, and leaves of C. procera, collected from the desert of Saudi Arabia, led to the isolation of one new lignan 7′-methoxy-3′-O-demethyl-tanegool-9-O-β-D-glucopyranoside and five known compounds from the flowers, four compounds from leaves, and a flavonoid glycoside and a lignan glycoside from the fruits. The structures of compounds were determined by spectroscopic techniques. Ethanol extracts of the three parts of C. procera were evaluated for their antiulcer activity and we found that the leaf extract possessed a powerful antiulcer activity which could be considered as a promising drug candidate. All the extracts and the isolated compounds were evaluated for their cytotoxic activity against MCF-7, HCT-116, HepG-2, and A-549 human cancer cell lines. Compound 2 was highly active on all the cell lines, whereas compounds 5 and 11 were more selective on colon and liver cell lines. Compound 10 demonstrated a significant activity on liver and lung cancer cell lines

Dialog chatbot as an interactive online tool in enhancing ESP vocabulary learning

Purpose – Based on an experimental study on English for Specific Purposes (ESP) students, at the Business Department at the University of Bisha, the purpose of the study is to examine the effect of chatbot use on learning ESP in online classrooms during COVID-19 and find out how Dialogflow chabot can be a useful and interactive online platform to help ESP learners in learning vocabulary well. Design/methodology/approach – The research paper is based on an experimental study of two groups, an experiential group and a controlled group. Two tests were carried out. Pre-tests and post-test of vocabulary knowledge were conducted for both groups to explore the usefulness of using the Dialogflow chatbot in learning ESP vocabulary. A designed chatbot content was prepared and included all the vocabulary details related to words' synonyms and a brief explanation of words’ meanings. An informal interview is another tool used in the study. The purpose of using the interview with the participants was to elicit more data from the participants about using the chatbot and about how and in what aspects chatbot using the conversational program was useful and productive. Findings – The findings of the study explored that the use of chatbots plays a major role in enhancing and learning ESP vocabulary. That was clear as the results showed that the students who used the chatbot Dialogflow in the experimental group outperformed their counterparts in the control group. Research limitations/implications – The study displays an important pedagogical implication as the use of chatbots could be applied in several settings to improve language learning in general or learning ESP courses in particular. Chatbot creates an interesting environment to foster build good interactions where negotiation of meaning takes place clearly seems to be of great benefit to help learners advance in their L2 lexical development. Originality/value – Examining and exploring whether the use of chatbots plays a major role in enhancing and learning ESP vocabulary in English as Foreign Language setting

Data-driven, participatory characterization of farmer varieties discloses teff breeding potential under current and future climates

In smallholder farming systems, traditional farmer varieties of neglected and underutilized species (NUS) support the livelihoods of millions of growers and consumers. NUS combine cultural and agronomic value with local adaptation, and transdisciplinary methods are needed to fully evaluate their breeding potential. Here, we assembled and characterized the genetic diversity of a representative collection of 366 Ethiopian teff (Eragrostis tef) farmer varieties and breeding materials, describing their phylogenetic relations and local adaptation on the Ethiopian landscape. We phenotyped the collection for its agronomic performance, involving local teff farmers in a participatory variety evaluation. Our analyses revealed environmental patterns of teff genetic diversity and allowed us to identify 10 genetic clusters associated with climate variation and with uneven spatial distribution. A genome-wide association study was used to identify loci and candidate genes related to phenology, yield, local adaptation, and farmers' appreciation. The estimated teff genomic offset under climate change scenarios highlighted an area around lake Tana where teff cropping may be most vulnerable to climate change. Our results show that transdisciplinary approaches may efficiently propel untapped NUS farmer varieties into modern breeding to foster more resilient and sustainable cropping systems

LC-MS analysis to determine the biodistribution of a polymer coated ilomastat ocular implant

Ilomastat is a matrix metalloproteinase inhibitor (MMPi) that has shown the potential to inhibit scarring (fibrosis) by mediating healing after injury or surgery. A long lasting ocular implantable pharmaceutical formulation of ilomastat is being developed to mediate the healing process to prevent scarring after glaucoma filtration surgery. The ilomastat implant was coated with water permeable and biocompatible phosphoryl choline polymer (PC1059) displayed extended slow release of ilomastat in vitro and in vivo. The ocular distribution of ilomastat from the implant in rabbits at day 30 post surgery was determined by the extraction of ilomastat and its internal standard marimastat from the ocular tissues, plasma, aqueous humour and vitreous fluid followed by capillary-flow liquid chromatography (cap-LC), the column effluent was directed into a triple quadrupole mass spectrometer operating in product scan mode. The lower limits of quantification (LLOQs) were 0.3 pg/μL for ocular fluids and plasma, and 3 pg/mg for ocular tissues. The extraction recoveries were 90-95% for ilomastat and its internal standard from ocular tissues. Ilomastat was found in ocular fluids and tissues at day 30 after surgery. The level of ilomastat was 18 times higher in the aqueous humour than vitreous humour. The concentration ranking of ilomastat in the ocular tissues was sclera > bleb conjunctiva > conjunctiva (rest of the eye) > cornea. Mass spectrometry analysis to confirm the presence of ilomastat in the ocular tissues and fluids at day 30 post-surgery establishes the extended release of ilomastat can be achieved in vivo, which is crucial information for optimisation of the ilomastat coated implant