Antiplatelet activity of the long-acting thromboxane receptor antagonist BMS 180,291 in monkeys

The effects of the novel TxA₂/prostaglandin endoperoxide (TP) receptor antagonist BMS 180,291 on platelet reactivity was determined ex vivo in conscious African green monkeys. Platelet aggregation responses to U-46,619 were decreased 50% and 100% at 23 to 24 hrs after BMS 180,291 oral doses of 1 and 3 mg/kg, respectively. In addition to inhibiting aggregation, a 3 mg/kg oral dose of BMS 180,291 also produced an 11±3-fold shift to the right in the U-46,619 concentration-response relationship for platelet shape change at 24 hrs after dosing. When the 3 mg/kg oral dose was continued for 11 days, the shift in this concentration-response relationship increased to 26±10- and 93±30-fold at 24 hrs after the 8th and 11th doses, respectively. This progressive inhibition corresponds to 93±3 and 99±1% blockade of platelet TP-receptors responsible for shape change, respectively. Comparable levels of TP-receptor blockade have been previously correlated with antithrombotic and antiischemic activities of TP-receptor antagonists in vivo. Platelet reactivity to U-46,619 had completely recovered on the 7th day after the final dose of BMS 180,291, indicating effective elimination from the circulation over this interval. In separate experiments, a 3-mg/kg i.v. dose of BMS 180,291 produced only marginal and transient hemodynamic effects in anesthetized African green monkeys. Overall, these data demonstrate that BMS 180,291 given orally once a day produces a sustained and therapeutically-relevant level of TP-receptor antagonism.     

Energy conservation and uncoupling in mitochondria

Energy conservation and uncoupling in mitochondria are examined in the light of three important new findings: (a) Studies with the photoaffinity-labeling uncoupler 2-azido-4-nitrophenol have shown that mitochondria contain a specific uncoupler binding site (apparently a polypeptide of M_r = 30,000 ± 10%). (b) This site fractionates into an enzyme complex (complex V), which is capable of oligomycin- and uncoupler-sensitive ATP-Pi exchange. It is absent from electron transfer complexes I, III, and IV, which represent segments of the respiratory chain containing coupling sites 1, 2, and 3, respectively. (c) Trinitrophenol is a membrane-impermeable uncoupler (uncouples submitochondrial particles, but not mitochondria) and a poor protonophore. There is an excellent correlation between the uncoupling potencies and the affinities of uncouplers for the mitochondrial uncoupler-binding site. There is no correlation between uncoupling potency and protonophoric activity of uncouplers when a membrane-permeable uncoupler is compared with a membrane-impermeable one.     

Research and effectiveness of anti-viral drugs against COVID-19; global public intervention to prevent coronavirus and to improve human health

Since the first case report on COVID-19, its transmission took place rapidly across the globe. Currently, it is reported to be spread into a total of 216 countries and territories. The suppression on industrial and gasoline burning activities accompanied after COVID-19 lock down favorably boosted the nature to restore its deteriorated sections such as in air with the improved Air quality index and in water bodies with the natural tone of purity. Increased use of anti-viral drugs along with herbal therapies has been observed at mass scale as global intervention to prevent the disease. The use of personal protective equipment and disinfection strategies for the control of pandemic has dramatically increased the pollution of plastic and medical waste. This article aims to forecast and highlight the evidence-based impact/changes (+ive and -ive) of coronavirus on the environment, global interventions to prevent the disease along with the levels of effectiveness of personal used protective equipment to stop the spread of coronavirus.     

Endoscopic Management of Genitourinary Foreign Bodies

Retrieval of foreign bodies from the genitourinary system, most commonly inserted for sexual satisfaction or as a result of a psychiatric illness, can pose a significant surgical challenge. Due to their breadth of size, shape, and location within the genitourinary system, endoscopic management can be difficult. Here, we review the management of four cases of foreign object insertion into the genitourinary system and their outcomes and management.Key words: Foreign body insertion, Sounding, Genitourinary foreign object, Endoscopic extractionForeign objects within the genitourinary tract present a challenging urologic finding due to the diversity and breadth of presentation. Although many objects are easily removed, more complex approaches may be required depending on the size, shape, and location of the object.^1,2 In this case series, we discuss the endoscopic management of four patients who presented with foreign bodies in the urethra. Two patients inserted beads into their genitourinary tract for the purpose of sexual stimulation and two patients had a history of psychiatric illness with multiple insertions of a diverse range of foreign objects. In all four cases, endoscopic management was successful in removing the objects, with no need for an open approach such as perineal urethrotomy or open cystostomy. In case 2, in which an open approach was attempted at an outside hospital, this open approach was associated with intraoperative complications.     

Synthesis and DNA Binding Properties of a New Benzo[f]Imidazo[1,5b]-Isoquinoline-Butan-1,2-Diol Derivative

A benzo[f]imidazo[1,5b]-isoquinoline derivative 4 with a 1,2-butandiol linker was prepared by reaction of a trimethylsilylated 5-naphthylidenehydantoin 3 with a 2,3-dideoxy-D-glycero-pentafuranoside 2 in 22% yield. After deprotection, the resulting compound 5 was converted to a DMT protected phosphoramidite building block 7 for standard DNA synthesis. DNA/DNA, DNA/RNA duplexes with 5 inserted as bulges were destabilized, except when the new amidite was used for the synthesis of a zipping duplex.     

Synthesis,Conformational and Configurational Studies of Some New Acetylated Glycosides of 2-Thio-3-aryl-4(3H)-quinazolinones,Their Thiono and 3,1-Benzothiazin-2,4-dithione

Abstract

A series of some new acetylated S-glycosides of 2-thioxoquinazolin-4-ones, their thiono analogues and 3,1-benzothazin-2,4-dithione derivatives, including a D-glucose and a D-galactose derivatives and a D-xylose, and an L-arabinose derivatives have been synthesized. The conformation and configuration of these carbohydrate derivatives were determined by analysing their ¹H and ¹³C NMR chemical shifts and coupling constants. The biological activity of these compounds has been studied.     

Theoretical investigations on the mechanistic pathway of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines

The mechanism of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines 1 has been studied using quantum chemistry methods. Geometries of reactants, transition states and products have been optimized at the B3LYP/6-311++G(2d,2p) level. Relative energies for various stationary points have been determined and reaction identified by IRC calculations. The results show that thermal rearrangements occur in three ways. Firstly, the transition state TS ₁ in which a hydrogen atom of methyl groups migrates from primary carbon to oxygen of amid group to give the N-methallylamide 2. The second is via the transition state TS ₂ in which the attack of oxygen to the tertiary carbon yields the oxazoline 3. The third is via the transition state TS ₃ in which a hydrogen migrate from the secondary carbon to oxygen to give the vinylamide 4. In order to get insights into the factors determining the exact nature of its interactions with electrophiles, the application of reactivity parameters derived from density functional theory in a local sense, in particular the softness and Fukui function, to interpret and predict the mechanisms of the thermal decomposition of the N-acyl-2,2-dimethylaziridines 1, has been discussed.     

Differentiation of Fanconi anemia and aplastic anemia using mitomycin C test in Tunisia

Fanconi anemia (FA) is a recessive chromosomal instability syndrome that is clinically characterized by multiple symptoms. Chromosome breakage hypersensitivity to alkylating agents is the gold standard test for FA diagnosis. In this study, we provide a detailed laboratory protocol for accurate assessment of FA diagnosis based on mitomycin C (MMC) test. Induced chromosomal breakage study was successful in 171 out of 205 aplastic anemia (AA) patients. According to the sensitivity of MMC at 50 ng/ml, 38 patients (22.22%) were diagnosed as affected and 132 patients (77.17%) as unaffected. Somatic mosaicism was suspected in an 11-year-old patient with a FA phenotype. Twenty-six siblings of FA patients were also evaluated and five of them (19.23%) were diagnosed as FA. From this study, a standard protocol for diagnosis of FA was developed. It is routinely used as a diagnostic test of FA in Tunisia.     

Malyngamide 4, a new lipopeptide from the Red Sea marine cyanobacterium Moorea producens (formerly Lyngbya majuscula)

In our continuing effort to discover new drug leads from Red Sea marine organisms, a sample of the marine cyanobacterium Moorea producens (previously Lyngbya majuscula) was investigated. Bioassay-directed purification of a tumor cell-growth inhibitory fraction of the organic extract of the Red Sea cyanobacterium afforded a new compound, malyngamide 4 (1), together with five previously reported compounds, malyngamide A (2) and B (3), (S)-7-methoxytetradec-4(E)-enoic acid (lyngbic acid, 4), aplysiatoxin (5) and debromoaplysiatoxin (6). Assignment of the planar structures of these compounds was based on extensive analysis of one- and two-dimensional NMR spectra and high-resolution mass spectrometric data. The isolated compounds were evaluated for their inhibitory activity against three cancer cell lines. In addition, the antibacterial activity of the compounds against Mycobacterium tuberculosis H₃₇Rv ATCC 27294 (H₃₇Rv) was evaluated. Lyngbic acid (4) was the most active against M. tuberculosis, while malyngamides 4 (1) and B (3) moderately inhibited the cancer cell lines. The other compounds were deemed inactive at the test concentrations.