MARVEL analysis of high-resolution rovibrational spectra of 13 C 16 O 2 .

A set of empirical rovibrational energy levels, obtained through the MARVEL (measured active rotational-vibrational energy levels) procedure, is presented for the 13 C 16 O 2 isotopologue of carbon dioxide. This procedure begins with the collection and analysis of experimental rovibrational transitions from the literature, allowing for a comprehensive review of the literature on the high-resolution spectroscopy of 13 C 16 O 2 , which is also presented. A total of 60 sources out of more than 750 checked provided 14,101 uniquely measured and assigned rovibrational transitions in the wavenumber range of 579-13,735 cm - 1 . This is followed by a weighted least-squares refinement yielding the energy levels of the states involved in the measured transitions. Altogether 6318 empirical rovibrational energies have been determined for 13 C 16 O 2 . Finally, estimates have been given for the uncertainties of the empirical energies, based on the experimental uncertainties of the transitions. The detailed analysis of the lines and the spectroscopic network built from them, as well as the uncertainty estimates, all serve to pinpoint possible errors in the experimental data, such as typos, misassignment of quantum numbers, and misidentifications. Errors found in the literature data were corrected before including them in the final MARVEL dataset and analysis.

Aeromonas hydrophila induced necrotizing fasciitis following laparoscopic cholecystectomy.

Necrotizi ng fasciit is [NF] i s a m ultifaceted disease of the muscle fascia and body tissues which demands the earliest intervention. Past reviews have documented ver y few cases of Aeromonas Hydroph ila [AH] induced N F fol lo wing abdominal surgery. AH can cause fatal NF as seen in a 72 year old female patient reported at Liaquat National Hospital &Medical College; a ter tiary care center in Karachi, Pakistan on 2nd April, 2022. She had a k nown comorbidity of hypertension and presented with the chief complaint of symptomatic gallstones for which she unde rwent Laparoscopic Cholecystectomy (LAPCHOL). She developed NF of the lower ab domen post- oper atively. Following uneventful Laparoscopic Cholecystectomy our pati ent presented to the ER two days later with severe lower abdo minal pain and overlyi ng celluliti s. Fasc io to my revealed extensive myonecrosis with necrotizing soft tissue in fe ction. Despite u ndergoing extensive surgical debr idement and broad spectr um antibi ot ic administration; the patient died in the ICU on the fifth postoperat ive day followi ng septic complications. Histopathologica l an alysis, confirmed i nflammat ion and necrosis. Culture sensitivity of the debrided tissue revealed AH. Approach should lie towards analyzing the behaviour of such microbes in high risk patients through collective case studies. This is the first clinical case showcasing such parameters e ncountered in the General Surger y Department.

Medical morbidity and risk of general hospital admission associated with concurrent anorexia nervosa and COVID-19: An observational study.

OBJECTIVE: Investigate medical morbidity and risk of general hospital admission for patients with concurrent coronavirus disease 2019 (COVID-19) and anorexia nervosa (AN) who have not received severe acute respiratory syndrome coronavirus 2 vaccination. METHODS: United Kingdom eating disorders clinicians contributed to a database of patients with an eating disorder and COVID-19. We used this to investigate demography, symptoms, hospitalization, treatment, and outcomes for those with AN. RESULTS: We describe data for 49 patients (median age 21.5 years [interquartile range 17.0-33.5], 46 female) including 36 adults and 13 under-18-year-olds. Three (6.1% [95% confidence interval 1.3%-17.9]) were admitted to a general hospital. For this sample, the expected age-standardized hospital admission rate per COVID-19 case (based on the general population of England) was 2.6% and therefore not significantly different to the hospitalization rate we observed. Three (including two of those admitted to hospital) contracted pneumonia. One had severe pneumonia and was admitted to an intensive care unit. No deaths or use of mechanical ventilation were recorded. DISCUSSION: To our knowledge, this represents the first study investigating medical morbidity or frequency of hospitalization for patients with COVID-19 and AN. We did not find evidence that patients with AN are at increased risk of severe COVID-19. PUBLIC SIGNIFICANCE: Medical morbidity and risk of hospitalization associated with concurrent COVID-19 and anorexia nervosa (AN) had not, to our knowledge, been studied before. We used a database of patients with eating disorders and COVID-19 (to which United Kingdom clinicians had contributed) to investigate presentation, treatment, outcomes, and COVID-19 severity for those with AN and COVID-19. We did not find evidence that patients with AN are at increased risk of severe COVID-19.

Synthesis, Antioxidant, Molecular Docking and DNA Interaction Studies of Metal-Based Imine Derivatives.

Currently, numerous ongoing studies are investigating the interaction of free radicals with biological systems, such as lipids, DNA and protein. In the present work, synthesis, characterization, antioxidant, DNA binding and molecular docking studies of Schiff base ligand and its Ni(II), Co(II), Cu(II) and Zn(II) were evaluated. The metal complexes have shown significant dose-dependent antioxidant activities higher than those of the free ligand but lesser than those of the standard antioxidant, ascorbic acid. The DNA binding constants (Kb) were found in the order Zn(pimp)2 {9.118 × 105 M-1} > H-pimp {3.487 × 105 M-1} > Co(pimp)2 {3.090 × 105 M-1} > Ni(pimp)2 {1.858 × 105 M-1} > Cu(pimp)2 {1.367 × 105 M-1}. Binding constants (Kb) values calculated from the molecular docking analysis were found to be in close agreement with the experimental results. The obtained results indicate the importance of synthesis complexes as a source of synthetic antioxidants and anticancer drugs.

Cannabinoid and Opioid Receptor Affinity and Modulation of Cancer-Related Signaling Pathways of Machaeriols and Machaeridiols from Machaerium Pers.

Machaeriols and machaeridiols are unique hexahydrodibenzopyran-type aralkyl phytocannabinoids isolated from Machaerium Pers. Earlier studies of machaeriol A (1) and B (2) did not show any affinity for cannabinoid receptor 1 (CB1 or CNR1), although they are structural analogs of psychoactive hexahydrocannabinol. This study comprehensively reports on the affinities of isolated Machaerium Pers. compounds, namely machaeriol A-D (1-4) and machaeridiol A-C (5-7), against cannabinoid (CB1 and CB2) and opioid (κ, δ and µ) receptors. Among the isolated compounds, machaeriol D (4) and machaeridiol A-C (5-7) showed some selective binding affinity for the CB2 receptor, using a radioligand binding assay, with Ki values of >1.3, >1.77, >2.18 and >1.1 µM, respectively. On the other hand, none of the compounds showed any binding to the CB1 receptor. Due to recent reports on the anticancer potential of the endocannabinoid system, compounds 1-7 were tested against a battery of luciferase reporter gene vectors that assess the activity of many cancer-related signaling pathways, including Stat3, Smad2/3, AP-1, NF-κB, E2F, Myc, Ets, Notch, FoxO, Wnt, Hedgehog and pTK in HeLa and T98G glioblastoma cells. Complete dose-response curves have been determined for each compound in both of these cell lines, which revealed that machaeridiol 6 displayed activities (IC50 in µM in HeLa and T98G cells) towards Stat3 (4.7, 1.4), Smad2/3 (1.2, 3.0), AP-1 (5.9, 4.2), NF-κB (0.5, 4.0), E2F (5.7, 0.7), Myc (5.3, 2.0), ETS (inactive, 5.9), Notch (5.3, 4.6), Wnt (4.2, inactive) and Hedgehog (inactive, 5.0). Furthermore, a combination study between machaeriol C (3) and machaeridiol B (6) displayed additive effects for E2F, ETS, Wnt and Hedgehog pathways, where these compounds individually were either minimally active or inactive. None of the compounds inhibited luciferase expression driven by the minimal thymidine kinase promoter (pTK), indicating the lack of general cytotoxicity for luciferase enzyme inhibition at the 50 µM concentration in both of these cell lines. The significance of the inhibition of these signaling pathways via machaeridiol 5-7 and their cross-talk potential has been discussed.

Genotoxicity and cytotoxicity potential of organoselenium compounds in human leukocytes in vitro.

In the current work, cytotoxicity and genotoxicity of different organoselenium compounds were examined using Trypan blue exclusion and alkaline comet assays with silver staining respectively. Leukocytes were subjected to a 3-hour incubation with organoselenium compounds at concentrations of 1, 5, 10, 25, 50, and 75 µM, or with the control vehicle (DMSO), at a temperature of 37 °C. The viability of the cells was evaluated using the Trypan blue exclusion method, while DNA damage was analyzed through the alkaline comet assay with silver staining. The exposure of leukocytes to different organoselenium compounds including i.e. (Z)-N-(pyridin-2-ylmethylene)-1-(2-((2-(1-((E)-pyridin-2-ylmethyleneamino)ethyl)phenyl)diselanyl)phenyl)ethanamine (C1), 2,2'(1Z,1'E)-(1,1'-(2,2'-diselanediylbis(2,1-phenylene))bis(ethane-1,1-diyl)) bis(azan-1-yl-1-ylidene)bis -methan-1-yl-1-ylidene)diphenol (C2), and dinaphthyl diselenide (NapSe)2, At concentrations ranging from 1 to 5 µM, no significant DNA damage was observed, as indicated by the absence of a noteworthy increase in the Damage Index (DI). Our results suggest that the organoselenium selenium compounds tested were not genotoxic and cytotoxic to human leukocytes in vitro at lower concentration. This study offers further insights into the genotoxicity profile of these organochalcogens in human leukocytes. Their genotoxicity and cytotoxicity effects at higher concentration are probably mediated through reactive oxygen species generation and their ability to catalyze thiol oxidation.

Metaplastic Reinforcement of Long-Term Potentiation in Hippocampal Area CA2 by Cholinergic Receptor Activation.

Hippocampal CA2, an inconspicuously positioned area between the well-studied CA1 and CA3 subfields, has captured research interest in recent years because of its role in social memory formation. However, the role of cholinergic inputs to the CA2 area for the regulation of synaptic plasticity remains to be fully understood. We show that cholinergic receptor activation with the nonselective cholinergic agonist, carbachol (CCh), triggers a protein synthesis-dependent and NMDAR-independent long-term synaptic depression (CCh-LTD) at entorhinal cortical (EC)-CA2 and Schaffer collateral (SC)-CA2 synapses in the hippocampus of adult male Wistar rats. The activation of muscarinic acetylcholine receptors (mAChRs) is critical for the induction of CCh-LTD with the results suggesting an involvement of M3 and M1 mAChRs in the early facilitation of CCh-LTD, while nicotinic AChR activation plays a role in the late maintenance of CCh-LTD at CA2 synapses. Remarkably, we find that CCh priming lowers the threshold for the subsequent induction of persistent long-term potentiation (LTP) of synaptic transmission at EC-CA2 and the plasticity-resistant SC-CA2 pathways. The effects of such a cholinergic-dependent synaptic depression on subsequent LTP at EC-CA2 and SC-CA2 synapses have not been previously explored. Collectively, the results demonstrate that CA2 synaptic learning rules are regulated in a metaplastic manner, whereby modifications triggered by prior cholinergic stimulation can dictate the outcome of future plasticity events. Moreover, the reinforcement of LTP at EC inputs to CA2 following the priming stimulus coexists with concurrent sustained CCh-LTD at the SC-CA2 pathway and is dynamically scaled by modulation of SC-CA2 synaptic transmission.SIGNIFICANCE STATEMENT The release of the neuromodulator acetylcholine is critically involved in processes of hippocampus-dependent memory formation. Cholinergic afferents originating in the medial septum and diagonal bands of Broca terminating in the hippocampal area CA2 might play an important role in the modulation of area-specific synaptic plasticity. Our findings demonstrate that cholinergic receptor activation induces an LTD of synaptic transmission at entorhinal cortical- and Schaffer collateral-CA2 synapses. This cholinergic activation-mediated LTD displays a bidirectional metaplastic switch to LTP on a future timescale. This suggests that such bidirectional synaptic modifications triggered by the dynamic modulation of tonic cholinergic receptor activation may support the formation of CA2-dependent memories given the increased hippocampal cholinergic tone during active wakefulness observed in exploratory behavior.

Synthesis, characterization, antioxidant, antileishmanial, anticancer, DNA and theoretical SARS-CoV-2 interaction studies of copper(II) carboxylate complexes.

Copper(II) carboxylate complexes [Cu2(OOCR)4L2] (1) and [Cu2(OOCR`)4OCO(R`)CuL2]n (2), where L = 2-methyl pyridine, R = 2-chlorophenyl acetate and R` = 2-fluorophenyl acetate were synthesized and characterized by FT-IR spectroscopy and single crystal X-ray analysis. Complex 1 exhibits the typical paddlewheel array of a dinuclear copper(II) complex with carboxylate ligands. In complex 2, this scaffold is further extended into a polymeric arrangement based on alternate paddlewheel and square planar moieties with distinct coordination spheres. The complexes showed better 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging activities and have been found to be more potent antileishmanial agents than their corresponding free ligand acid species. UV-Vis absorption titrations revealed good DNA binding abilities {Kb = 9.8 × 104 M-1 (1) and 9.9 × 104 M-1 (2)} implying partial intercalation of the complexes into DNA base pairs along with groove binding. The complexes displayed in vitro cytotoxic activity against malignant glioma U-87 (MG U87) cell lines. Computational docking studies further support complex-DNA binding by intercalation. Molecular docking investigations revealed probable interactions of the complexes with spike protein, the nucleocapsid protein of SARS-CoV-2 and with the angiotensin converting enzyme of human cells.

Genotype-Phenotype Study of ß-Thalassemia Patients in Sabah.

ß-thalassemia is a serious public health problem in Sabah due to its high prevalence. This study aimed to investigate the effects of different types of ß-globin gene mutations, coinheritance with α-globin gene mutations, XmnI-Gγ, and rs368698783 polymorphisms on the ß-thalassemia phenotypes in Sabahan patients. A total of 111 patients were included in this study. The sociodemographic profile of the patients was collected using a semi-structured questionnaire, while clinical data were obtained from their medical records. Gap-PCR, ARMS-PCR, RFLP-PCR, and multiplex PCR were performed to detect ß- and α-globin gene mutations, as well as XmnI-Gγ and rs368698783 polymorphisms. Our data show that the high prevalence of ß-thalassemia in Sabah is not due to consanguineous marriages (5.4%). A total of six different ß-globin gene mutations were detected, with Filipino ß°-deletion being the most dominant (87.4%). There were 77.5% homozygous ß-thalassemia patients, 16.2% compound heterozygous ß-thalassemia patients, and 6.3% ß-thalassemia/Hb E patients. Further evaluation on compound heterozygous ß-thalassemia and ß-thalassemia/Hb E patients found no concomitant α-globin gene mutations and the rs368698783 polymorphism. Furthermore, the XmnI-Gγ (-/+) genotype did not demonstrate a strong impact on the disease phenotype, as only two of five patients in the compound heterozygous ß-thalassemia group and two of three patients in the ß-thalassemia/Hb E group had a moderate phenotype. Our findings indicate that the severity of the ß-thalassemia phenotypes is closely related to the type of ß-globin gene mutations but not to the XmnI-Gγ and rs368698783 polymorphisms.

A stable home-base promotes allocentric memory representations of episodic-like everyday spatial memory.

A key issue in neurobiological studies of episodic-like memory is the geometric frame of reference in which memory traces of experience are stored. Assumptions are sometimes made that specific protocols favour either allocentric (map-like) or egocentric (body-centred) representations. There are, however, grounds for suspecting substantial ambiguity about coding strategy, including the necessity to use both frames of reference occasionally, but tests of memory representation are not routinely conducted. Using rats trained to find and dig up food in sandwells at a particular place in an event arena (episodic-like 'action-where' encoding), we show that a protocol previously thought to foster allocentric encoding is ambiguous but more predisposed towards egocentric encoding. Two changes in training protocol were examined with a view to promoting preferential allocentric encoding-one in which multiple start locations were used within a session as well as between sessions; and another that deployed a stable home-base to which the animals had to carry food reward. Only the stable home-base protocol led to excellent choice performance which rigorous analyses revealed to be blocked by occluding extra-arena cues when this was done after encoding but before recall. The implications of these findings for studies of episodic-like memory are that the representational framework of memory at the start of a recall trial will likely include a path direction in the egocentric case but path destination in the allocentric protocol. This difference should be observable in single-unit recording or calcium-imaging studies of spatially-tuned cells.

Late clinical outcomes of lambre versus amplatzer occluders for left atrial appendage closure.

INTRODUCTION: The LAmbre (LifeTech Scientific, Shenzhen, China) is a novel occluder for left atrial appendage closure (LAAC) in patients with atrial fibrillation. This study compares late clinical outcomes of LAmbre and the established Amplatzer devices (Abbott, St Paul, MN). METHODS: Between 2012 and 2018, 265 consecutive patients underwent LAAC with LAmbre and Amplatzer devices at a single center. After a 3:1 propensity score matching, 40 (LAmbre) vs 107 (Amplatzer) patients were compared by the primary efficacy endpoint of all-cause stroke, systemic embolism and cardiovascular/unexplained death, the primary safety endpoint of major periprocedural complications and major bleeding events at follow-up, and the combined hazard endpoint, a composite of all the above-mentioned hazards. RESULTS: The mean age 75.6 ± 8.9 (LAmbre) vs 75.5 ± 9.0 (Amplatzer) years, CHA2 DS2 -VASc score 4.8 ± 1.7 vs 4.8 ± 1.7 and HAS-BLED score 3.1 ± 0.9 vs 3.2 ± 0.8 were similar. After 3.6 ± 1.9 vs 2.5 ± 1.4 years, the clinical efficacy (12/146, 8.2% [LAmbre] vs 28/266, 10.5% [Amplatzer]; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.38-1.40; P = .34) and safety (5/146, 3.4% vs 14/266, 5.3%; HR, 0.47; 95% CI, 0.14-1.6; P = .22), as well as the combined hazard endpoint (15/146, 10.3% vs 36/266, 13.6%; HR, 0.67; 95% CI, 0.36-1.25; P = .21) were comparable. CONCLUSION: In the presented report, in patients with nonvalvular atrial fibrillation, the LAmbre offered similar long-term efficacy and safety in comparison to Amplatzer devices.

Long-term clinical outcomes of Amplatzer cardiac plug versus Amulet occluders for left atrial appendage closure.

OBJECTIVES: To compare long-term clinical outcomes after left atrial appendage closure with the Amplatzer Cardiac Plug (ACP) and Amulet. BACKGROUND: The Amulet was designed to improve clinical outcomes of first-generation ACP. METHODS: Three Amplatzer registries (Bern, Coburg, Zurich), with enrollment of patients from 2009 to 2018, were retrospectively analyzed. The primary safety endpoint was a composite of major peri-procedural complications and major bleedings, the primary efficacy endpoint included stroke, systemic embolism, and cardiovascular/unexplained death. The net clinical benefit was a combination of all above-mentioned hazards. RESULTS: A total of consecutive 563 patients (344 ACP vs. 219 Amulet) with a mean follow-up of 2.9 ± 1.6 and 1.9 ± 0.9 years were included. Mean age (74.4 ± 9.9 [ACP] vs. 74.4 ± 9.1 [Amulet] years), stroke (CHA2 DS2 -VASc score 4.4 ± 1.6 vs. 4.6 ± 1.7), and bleeding risk (HAS-BLED score 3.2 ± 1.1 vs. 3.2 ± 0.9) were comparable. The primary endpoints of efficacy (72/998, 7.2% [ACP] vs. 43/417, 10.3% [Amulet]; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.44-1.02, p = .062), safety (40/998, 4.0% vs. 18/417, 4.3%; HR, 1.15; 95% CI, 0.53-2.51, p = .72), and the net clinical benefit (101/998, 10.1% vs. 55/417, 13.4%; HR, 0.73; 95% CI, 0.49-1.07, p = .11) were similar. CONCLUSION: In the long term, left atrial appendage closure with first and second-generation Amplatzer devices provided similar efficacy, safety, and net clinical benefit. Clinical outcomes may be rather determined by implantation technique and hemodynamics, but not by the design modifications of the Amulet.

Propensity-matched comparison of antiplatelet versus anticoagulant after left atrial appendage closure with the Watchman.

BACKGROUND: Optimal antithrombotic therapy following left atrial appendage closure (LAAC) with the Watchman occluder remains uncertain. This study retrospectively compared clinical outcomes of a 3-month dual antiplatelet therapy (DAPT group) and a protocol of anticoagulation plus aspirin for 45 days followed by DAPT for 6 months (ACT group) after LAAC with the Watchman device. METHODS: Of two Watchman registries (Coburg and Lichtenfels hospitals, Germany), 220 and 304 consecutive patients with successful LAAC were included. Patients in Coburg hospital received DAPT while they received ACT in Lichtenfels. After a 1:1 propensity score matching, 174 (DAPT) versus 174 (ACT) patients were compared by use of the primary efficacy endpoint of thromboembolic events and cardiovascular/unexplained death, the primary safety endpoint of nonprocedural related major bleeding events at follow-up, and the combined hazard endpoint, a composite of all above-mentioned hazards. RESULTS: The mean age 77.5 ± 7.2 (DAPT) versus 77.3 ± 7.1 (ACT) years, CHA2 DS2 -VASc score 4.6 ± 1.5 versus 4.7 ± 1.6, and HAS-BLED score 3.3 ± 0.8 versus 3.3 ± 0.8 were similar. After 12 months, the clinical efficacy (13/174, 7.4% [DAPT] vs 11/174, 6.3% [ACT]; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.38-1.86; P = .66) and safety (6/174, 3.4% vs 8/174, 4.5%; HR, 0.86; 95% CI, 0.29-2.56; P = .79) as well as the combined hazard endpoint (18/174, 10.3% vs 18/174, 10.3%; HR,1.01; 95% CI, 0.53-1.95; P = .97) were comparable. CONCLUSIONS: This study suggests comparable efficacy and safety of 3-month DAPT versus 6 weeks ACT plus aspirin following LAAC with the Watchman.

Engineering Corynebacterium glutamicum for the de novo biosynthesis of tailored poly-γ-glutamic acid.

γ-Polyglutamic acid (γ-PGA) is a biodegradable polymer naturally produced by Bacillus spp. that has wide applications. Fermentation of γ-PGA using Bacillus species often requires the supplementation of L-glutamic acid, which greatly increases the overall cost. Here, we report a metabolically engineered Corynebacterium glutamicum capable of producing γ-PGA from glucose. The genes encoding γ-PGA synthase complex from B. subtilis (pgsB, C, and A) or B. licheniformis (capB, C, and A) were expressed under inducible promoter Ptac in a L-glutamic acid producer C. glutamicum ATCC 13032, which led to low levels of γ-PGA production. Subsequently, C. glutamicum F343 with a strong L-glutamic acid production capability was tested. C. glutamicum F343 carrying capBCA produced γ-PGA up to 11.4 g/L, showing a higher titer compared with C. glutamicum F343 expressing pgsBCA. By introducing B. subtilis glutamate racemase gene racE under Ptac promoter mutants with different expression strength, the percentage of L-glutamic acid units in γ-PGA could be adjusted from 97.1% to 36.9%, and stayed constant during the fermentation process, while the γ-PGA titer reached 21.3 g/L under optimal initial glucose concentrations. The molecular weight (Mw) of γ-PGA in the engineered strains ranged from 2000 to 4000 kDa. This work provides a foundation for the development of sustainable and cost-effective de novo production of γ-PGA from glucose with customized ratios of L-glutamic acid in C. glutamicum.

Cardiac Dysfunction in Neurocritical Care: An Autonomic Perspective.

A number of neurologic disorders can cause cardiac dysfunction by involving the conductive system and contractile apparatus of the heart. This is especially prominent in the neurocritical care setting where the spectrum of cardiac dysfunction due to acute neurologic injury ranges from trivial and isolated electrocardiographic changes to malignant arrhythmias and sudden death (Table 1). The mechanism of these cardiac complications is complex and not fully understood. An understanding of the neuroanatomical structures and pathways is of immense importance to comprehend the underlying pathophysiology that culminates as cardiac damage and dysregulation. Once the process is initiated, it can complicate and adversely affect the outcome of primary neurologic conditions commonly seen in the neurocritical care setting. Not only are these cardiac disorders under-recognized, there is a paucity of data to formulate evidence-based guidelines regarding early detection, acute management, and preventive strategies. However, certain details of clinical features and their course combined with location of primary neurologic lesion on neuroimaging and data obtained from laboratory investigations can be of great value to develop a strategy to appropriately manage these patients and to prevent adverse outcome from these cardiac complications. In this review, we highlight the mechanisms of cardiac dysfunction due to catastrophic neurologic conditions or due to stress of critical illness. We also address various clinical syndromes of cardiac dysfunction that occur as a result of the neurologic illness and in turn may complicate the course of the primary neurologic condition.

Acute oral toxicity and antioxidant studies of an amine-based diselenide.

BACKGROUND: Organochalcogen compounds have attracted the interest of a multitude of studies for their promising Pharmacological and biological activities. The antioxidant activity and acute toxicity of an organoselenium compound, 1-(2-(2-(2-(1-aminoethyl)phenyl)diselanyl)phenyl)ethanamine (APDP) was determined in mice. METHODS: Mice were randomly divided into four groups, with each group comprising of seven animals. Canola oil (1ml/kg of body weight) was administered to 1st group, while 2nd, 3rd & 4th groups were administered with 10 mg/kg, 30 mg/kg & 350 mg/kg of APDP respectively. APDP was administered by Intragastric gavage as a single oral dose. RESULTS: The APDP oral administration was found to be safe up to 350 mg/kg of body weight and no deaths of animals were recorded. The lethal dose 50 (LD50) for APDP was determined at 72 h and was estimated to be > 350 mg/kg. After acute treatment, all mice were sacrificed by decapitation to determine the antioxidant enzymes and lipid peroxidation values for the treated mice liver. No fluctuation in lipid peroxidation, vitamin C and non protein thiol (NPSH) levels was observed due to the administration of APDP. hepatic α-ALA-D activity, catalase (CAT), superoxide dismutase (SOD) and the biochemical parameters were evaluated. Experimental observation demonstrated that APDP protected Fe(II) induced thiobarbituric acid reactive substances (TBARS) production in liver homogenate significantly (p < 0.05). The administration of APDP (an amine-based diselenide) both in vitro and in vivo clearly demonstrated that this potential compound has no acute toxicity towards mice among all the tested parameter. CONCLUSION: On the basis of experimental results, it is concluded that APDP is a potential candidate as an antioxidant compound for studying pharmacological properties.

Possible involvement of transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the protective effect of caffeic acid on paraquat-induced oxidative damage in Drosophila melanogaster.

Paraquat (PQ) is a widely used herbicide with no antidote which is implicated in the pathogenesis of the Parkinson's disease. The present study then investigated the potential of caffeic acid (CA), a known antioxidant, cardioprotective and neuroprotective molecule to counteract oxidative stress mediated by PQ. In addition, molecular docking was performed to understand the mechanism underlying the inhibitory effect of CA against PQ poisoning. The fruit fly, Drosophila melanogaster, was exposed to PQ (0.44 mg/g of diet) in the absence or presence of CA (0.25, 0.5, 1 and 2 mg/g of died) for 7 days. Data showed that PQ-fed flies had higher incidence of mortality which was associated with mitochondrial dysfunction, increased free Fe(II) content and lipid peroxidation when compared to the control. Co-exposure with CA reduced mortality and markedly attenuated biochemical changes induced by PQ. The mechanism investigated using molecular docking revealed a strong interaction (-6.2 Kcal/mol) of CA with D. melanogaster transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2). This was characterized by the binding of CA to keap-1 domain of Nrf2. Taking together these results indicate the protective effect of CA against PQ-induced oxidative damage in D. melanogaster was likely through its coordination which hinders Nrf2-keap-1 binding leading to an increase of the antioxidant defense system.

TLC-bioautography identification and GC-MS analysis of antimicrobial and antioxidant active compounds in Musa × paradisiaca L. fruit pulp essential oil.

INTRODUCTION: The absence of microbial growth and resistance to oxidative deterioration in fruits of Musa × paradisiaca L. (bananas) is an indication of the presence of antimicrobial and antioxidant metabolites. OBJECTIVE: In order to investigate the secondary metabolomic spectrum as well as the active antimicrobial and antioxidants present in essential oils (EOs) from fruits of different geographical areas of M. × paradisiaca, gas chromatography-mass spectroscopy (GC-MS) principal component data correlation analysis is complemented with antimicrobial assays and phytochemical and bioautographic antioxidant fingerprints with thin layer chromatography (TLC). METHODOLOGY: An EO was obtained by steam distillation and subjected to GC-MS and TLC for metabolomic profiling from fruit pulp. The antimicrobial potential was tested in both Escherichia coli as a gram negative and Bacillus subtilis as a gram positive microbe. Potential antioxidant metabolites were identified through TLC-bioautography and GC-MS analysis of active zones. RESULTS: A maximum of 0.56% v/w EO was isolated from fruit pulps of M. × paradisiaca. Minimum inhibitory concentrations (MICs) against B. subtillis and E. coli were 0.25 and 0.35 µg/mL, respectively. Thus, 56 metabolites were identified through GC-MS. The major abundant antimicrobial metabolites found in EOs are α-thujene, γ-terpinene, α- and ß-pinene, sabinene, ß-myrcene, limonene, α-capaene, caryophyllene and (Z,E)-α farnesene. Aceteugenol, palmitic acid, stearic acid, palmitin, and stearin were identified as antioxidant metabolites. Principal component analysis of metabolite data reveals correlations and a clear separation based on metabolites obtained from various areas. CONCLUSION: The data generated using metabolic profiling and cluster analysis helped to identify antimicrobial and antioxidant compounds in M. × paradisiaca.

The Synthesis, Characterization, Cytotoxic Activity Assessment and Structure-Activity Relationship of 4-Aryl-6-(2,5-dichlorothiophen-3-yl)-2-methoxypyridine-3-carbonitriles.

A series of 2-methoxypyridine-3-carbonitrile (5a-i)-bearing aryl substituents were successfully synthesized in good yields by the condensation of chalcones (4a-i) with malononitrile in basic medium. The condensation process, in most cases, offers a route to a variety of methoxypyridine derivatives (6a-g) as side products in poor yields. All new compounds were fully characterized using different spectroscopic methods. Mass ESI-HMRS measurements were also performed. Furthermore, these compounds were screened for their in vitro cytotoxicity activities against three cancer cell lines; namely, those of the liver (line HepG2), prostate (line DU145) and breast (line MBA-MB-231). The cytotoxicity assessment revealed that compounds 5d, 5g, 5h and 5i exhibit promising antiproliferative effects (IC50 1-5 µM) against those three cancer cell lines.