Anatoxin-a(s), an anticholinesterase from the cyanobacterium Anabaena flos-aquae NRC-525-17

Anatoxin a(s) [antx-a(s)] given intraperitoneally to Sprague-Dawley rats at different doses (0.1-1.0 mg/kg) caused signs of severe cholinergic overstimulation. Assays of rat blood acetylcholinesterase (AChE) revealed a dose-dependent inhibition. The in vitro inhibition of electric eel acetylcholinesterase (AChE, E.C. 3.1.1.7) and horse serum butyrylcholinesterase (BUChE, E.C. 3.1.1.8) by antx-a(s) was time- and concentration-dependent. The inhibition of electric eel AChE follows first order kinetics, indicative of irreversible inhibition. The irreversibility of electric eel AChE inhibition was confirmed by a plot of Vmax versus total enzyme concentration [ET]. The kinetics of inhibition of cholinesterase by antx-a(s) supports the previous pharmacological findings that antx-a(s) is an anticholinesterase and that signs of intoxication by it are primarily due to cholinesterase inhibition.     

Effect of a low-dose endotoxin pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine in rats

The effect of endotoxin pretreatment (1 mg/kg body weight, i.p., once daily for 2 days) on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine has been studied in albino rats. When given alone, endotoxin did not produce any visibly discernible gastric lesions. It produced a significant augmentation of the gastric lesions produced by phenylbutazone and reserpine but did not significantly alter the ulcerogenicity of aspirin. The involvement of endogenous histamine formation and its release following phenylbutazone and reserpine administration and also in response to endotoxin pretreatment may be responsible for the exacerbation of gastric lesions induced by these drugs. Recent reports indicate the involvement of endorphins and platelet activating factor (PAF) in the ulcerogenic activity of endotoxin when used in high doses and their role in the potentiation of phenylbutazone- and reserpine-induced gastric lesions has to be worked out.     

Post‐COVID‐19 splenic infarction in a patient with chronic atrial fibrillation: A case report

We describe splenic infarction (SI), an infrequent condition, in an 82‐year‐old COVID‐19 patient with chronic atrial fibrillation (AF). COVID‐19 may cause thrombosis, and AF is a predisposing factor for splenic infarction. Suspicion of SI may be warranted in COVID‐19 patients with abdominal pain, especially if a predisposing factor exists.     

Flexural Performance of Encased Pultruded GFRP I-Beam with High Strength Concrete under Static Loading

There is an interesting potential for the use of GFRP-pultruded profiles in hybrid GFRP-concrete structural elements, either for new constructions or for the rehabilitation of existing structures. This paper provides experimental and numerical investigations on the flexural performance of reinforced concrete (RC) specimens composite with encased pultruded GFRP I-sections. Five simply supported composite beams were tested in this experimental program to investigate the static flexural behavior of encased GFRP beams with high-strength concrete. Besides, the effect of using shear studs to improve the composite interaction between the GFRP beam and concrete as well as the effect of web stiffeners of GFRP were explored. Encasing the GFRP beam with concrete enhanced the peak load by 58.3%. Using shear connectors, web stiffeners, and both improved the peak loads by 100.6%, 97.3%, and 130.8%, respectively. The GFRP beams improved ductility by 21.6% relative to the reference one without the GFRP beam. Moreover, the shear connectors, web stiffeners, and both improved ductility by 185.5%, 119.8%, and 128.4%, respectively, relative to the encased reference beam. Furthermore, a non-linear Finite Element (FE) model was developed and validated by the experimental results to conduct a parametric study to investigate the effect of the concrete compressive strength and tensile strength of the GFRP beam. The developed FE model provided good agreement with the experimental results regarding deformations and damaged patterns.     

Role of second-line systemic treatment post-docetaxel in metastatic castrate resistant prostate cancer- current strategies and future directions

Treatment of metastatic castrate resistant prostate cancer (mCRPC) after progression on docetaxel chemotherapy is a challenging clinical scenario with limited availability of treatment options. Re-treatment with docetaxel, either as monotherapy or in combination with other cytotoxics or targeted agents has shown durable responses. However, most docetaxel re-treatment studies have been either retrospective or early phase non-randomised studies which have not formally assessed Quality of life or survival gain with re-treatment. Despite limited evidence for efficacy of mitoxantrone in the second-line, it continues to remain widely used, largely due to lack of available suitable alternatives. Cabazitaxel in combination with prednisolone is the only chemotherapy to have shown a significant survival benefit and receive approval by the U.S. Food and Drug Administration for patients with mCRPC previously treated with a docetaxel-based regimen. Abiraterone acetate has recently demonstrated a significant improvement in survival when compared to placebo in patients with docetaxel-treated mCRPC. This review aims to summarize the current evidence and discuss future strategies for treatment of mCRPC patients following failure of docetaxel chemotherapy.     

Metabolic and pharmacological profiling of Penicillium claviforme by a combination of experimental and bioinformatic approaches

BackgroundPenicillium produces a wide range of structurally diverse metabolites with significant pharmacological impacts in medicine and agriculture. For the first time, a complete metabolome of Penicillium claviforme (P. claviforme) (FBP-DNA-1205) was studied alongside pharmacological research in this study.MethodsThe metabolic profile of P. claviforme fermented on Potato Dextrose Broth (PDB) was investigated in this work. The complete metabolomics studies of fungus were performed using GC-MS and LC-MS-QTOF techniques. An in vitro model was utilised to study the cytotoxic and antioxidant activities, while an in vivo model was employed to investigate the antinociceptive and acute toxicity activities. Molecular Operating Environment (MOE) software was used for molecular docking analysis.ResultsGC-MS study showed the presence of alkanes, fatty acids, esters, azo and alcoholic compounds. Maculosin, obtain, phalluside, quinoline, 4,4’-diaminostilbene, funaltrexamine, amobarbital, and fraxetin were among the secondary metabolites identified using the LC-MS-QTOF technique. The n-hexane fraction of P. claviforme displayed significant cytotoxic activity in vitro, with an LD50 value of 92.22 µgml⁻¹. The antinociceptive effects in vivo were dose-dependent significantly (p < .001). Interestingly, during the 72 h of investigation, no acute toxicity was demonstrated. In addition, a docking study of tentatively identified metabolites against the inflammatory enzyme (COX-2) supported the antinociceptive effect in an in silico model.ConclusionMetabolic profile of P. claviforme shows the presence of biologically relevant compounds in ethyl acetate extract. In addition, P. claviforme exhibits substantial antioxidant and cytotoxic activities in an in vitro model as well as antinociceptive activity in an in vivo model. The antinociceptive action is also supported by a molecular docking study. This research has opened up new possibilities in the disciplines of mycology, agriculture, and pharmaceutics.

Key messages

• The first time explored complete metabolome through GC-MS and LC-MS-QTOF.
• Both in vivo & in vitro pharmacological investigation of P. claviforme.
• In silico molecular docking of LC-MS-QTOF metabolites.

     

Bilateral proximal deep vein thrombosis and COVID‐19 in a patient with absence of inferior vena cava: A case report and review of literature

Bilateral proximal deep vein thrombosis (DVT) in the lower extremities of young patients should raise suspicion over pro‐thrombotic conditions and venous anatomical abnormalities, even in the presence of other precipitating factors, such as viral infection. The authors present a 33‐year‐old man with bilateral DVT and absence of inferior vena cava (AIVC), who also had concurrent COVID‐19, and discuss the management of this patient.     

Improved Shear Strength Prediction Model of Steel Fiber Reinforced Concrete Beams by Adopting Gene Expression Programming

In this study, an artificial intelligence tool called gene expression programming (GEP) has been successfully applied to develop an empirical model that can predict the shear strength of steel fiber reinforced concrete beams. The proposed genetic model incorporates all the influencing parameters such as the geometric properties of the beam, the concrete compressive strength, the shear span-to-depth ratio, and the mechanical and material properties of steel fiber. Existing empirical models ignore the tensile strength of steel fibers, which exercise a strong influence on the crack propagation of concrete matrix, thereby affecting the beam shear strength. To overcome this limitation, an improved and robust empirical model is proposed herein that incorporates the fiber tensile strength along with the other influencing factors. For this purpose, an extensive experimental database subjected to four-point loading is constructed comprising results of 488 tests drawn from the literature. The data are divided based on different shapes (hooked or straight fiber) and the tensile strength of steel fiber. The empirical model is developed using this experimental database and statistically compared with previously established empirical equations. This comparison indicates that the proposed model shows significant improvement in predicting the shear strength of steel fiber reinforced concrete beams, thus substantiating the important role of fiber tensile strength.     

The Effect of Dentifrice on Micro-Hardness,Surface Gloss,and Micro-Roughness of Nano Filled Conventional and Bulk-Fill Polymer Composite—A Micro Indentation and Profilometric Study

The aim of the present study was to evaluate the effect of brushing with two whitening dentifrices (Colgate Optic White (COW) and Colgate Optic White Charcoal (COC)) on surface gloss, micro-roughness, and micro-hardness of nanostructured hybrid conventional (Z350) and bulk-fill (Tetric N Ceram bulk-fill) polymer composite. In total, 96 disk samples using two nano-hybrid composite polymers (Z350 and Tetric N Ceram Bulk-fill) were prepared. All specimens were exposed to two different dentifrices (COW and COC), resulting in four main subgroups in the study. Specimens were assessed for surface gloss, micro-roughness (Ra), and micro-hardness using standardized methodology. Means and standard deviations of properties compared using paired t-test, one-way and two-way ANOVA, and post hoc test. The presence of dentifrices did not show any significant difference in micro-hardness values of Z350 (p > 0.05), whereas micro-hardness of bulk-fill composite significantly reduced on dentifrices exposure (p ≤ 0.05). Bulk-fill polymer composite showed significant reduction in gloss after dentifrice exposure (p < 0.05), however, Z350 showed no significant loss of gloss due to dentifrices (p > 0.05). A significant increase in Ra was observed for both resin materials after exposure to dentifrices (COC and COW). Conventional resin composite (Z350) showed comparable surface hardness and gloss before and after dentifrice exposure, however, micro-roughness increased significantly due to dentifrice exposure. Bulk-fill resin (Tetric N Ceram) showed significant loss of micro-hardness and gloss and increase in micro-roughness on dentifrice exposure. Conventional nano-hybrid composite polymer showed better durability in resisting loss of surface properties compared to bulk-fill resin polymer in the present experiment.