Release-Active Dilutions of Diclofenac Enhance Anti-inflammatory Effect of Diclofenac in Carrageenan-Induced Rat Paw Edema Model

The study was aimed to investigate the effect of technologically treated diclofenac (release-active dilutions of diclofenac (RAD of diclofenac)) on anti-inflammatory activity of diclofenac in carrageenan-induced rat paw edema model. Ninety male Wistar albino rats (6–8 weeks) divided into nine groups (n?=?10) were used. Anti-inflammatory activity was assessed at 1, 2, 3, 4, and 6 h after subplantar injection of carrageenan (0.1 ml of a 1 % solution in normal saline). Diclofenac alone was studied at 5 and 20 mg/kg, RAD of diclofenac alone at 7.5 ml/kg and their combination at 5 and 7.5 ml/kg, respectively. Diclofenac reduced (p?<?0.05 at least) paw edema at all time points. RAD of diclofenac enhanced (p?<?0.05) anti-inflammatory effect of diclofenac (5 mg/kg) at 2, 4, and 6 h on concurrent and at 2 and 4 h on sequential administration. Moreover at 2 h, anti-inflammatory effect of combination treatment reached values comparable to those of diclofenac (20 mg/kg). In conclusion, RAD of diclofenac enhanced anti-inflammatory effect of diclofenac.     

Lysosomal abnormalities during benzo(a)pyrene-induced experimental lung carcinogenesis – defensive role of capsaicin

The objective of the present study was to investigate whether lysosome is a target in benzo(a)pyrene-induced, oxidative stress-mediated lung cancer in Swiss albino mice and the plausible role of the phytochemical substance capsaicin in mitigating lysosomal damage. Oxidative stress was assessed based on the level of carbonyl content. The activities of lysosomal proteases like cathepsin-D, cathepsin-B, β- d -glucosidase, β- d -galactosidase, β- d -glucuronidase, β- d - N -acetylglucosaminidase and acid phosphatase were assessed to evaluate lysosomal function. Administration of benzo(a)pyrene (50 mg/kg body weight) to mice induced a increase in the activities of lysosomal enzymes and oxidative stress was evident by the increase in carbonyl content. Treatment with capsaicin (10 mg/kg body weight) decreased carbonyl content and restored the activities of lysosomal enzymes to near normalcy. Transmission electron microscopic study of lysosomes further showed the defensive action of capsaicin against the lysosomal damage caused in benzo(a)pyrene-induced lung cancer. From the present study, it can be concluded that lysosomal damage is an indispensable event in benzo(a)pyrene-induced lung cancer, and capsaicin was able to effectively prevent it, which proves the chemoprotective effect of capsaicin against benzo(a)pyrene-induced experimental lung carcinogenesis.     

An interesting case of Leigh-like syndrome

A 12-year-old female child with motor developmental delay presented with persistent vomiting, recurrent falls and unsteadiness in dark since 2 years of age. There was decline in scholastic performance, bulbar symptoms and aggravation of symptoms during intercurrent illness. Clinically, she had frontal and parietal lobar dysfunction, dysarthria, optic atrophy and LMN VII, IX, X, XII cranial nerve involvement. There was generalized hypotonia, distal muscle wasting, weakness, cerebellar signs and impaired vibration/position sense in distal extremities. Biochemical investigations revealed elevated serum/cerebrospinal fluid (CSF) lactate and CSF lactate pyruvate ratio. Neuroimaging demonstrated bilateral symmetrical T2 hyperintensities in basal ganglia, subcortical white matter, cerebellar hemispheres and posterior aspect of spinal cord. As certain atypical features like bilateral symmetrical T2 hyperintensities in subcortical white matter were also seen, metachromatic leukodystrophy was considered in differential diagnosis but ruled out by nerve biopsy. This case is reported for the presence of atypical neuroimaging features that are rarely found in Leigh''s disease.     

Studies on the impact of biosynthesized silver nanoparticles (AgNPs) in relation to malaria and filariasis vector control against Anopheles stephensi Liston and Culex quinquefasciatus Say (Diptera: Culicidae)

Biosynthesized nanoparticles have been achieved using environmentally acceptable plant extract and eco-friendly reducing and capping agents. The present study was based on assessments of the larvicidal activities to determine the efficacies of synthesized silver nanoparticles (AgNPs) using aqueous leaf extract of Vinca rosea (L.) (Apocynaceae) against the larvae of malaria vector Anopheles stephensi Liston and filariasis vector Culex quinquefasciatus Say (Diptera: Culicidae). Larvae were exposed to varying concentrations of aqueous extract of V. rosea and synthesized AgNPs for 24, 48, and 72 h. AgNPs were rapidly synthesized using the leaf extract of V. rosea, and the formation of nanoparticles was observed within 15 min. The results recorded from UV–Vis spectrum, Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) support the biosynthesis and characterization of AgNPs. The formation of the AgNPs synthesized from the XRD spectrum compared with the Bragg reflections at 2θ?=?29.36, 38.26, 44.51, 63.54, and 77.13° which can be indexed to the (121), (111), (200), (220), and (311) orientations, respectively, confirmed the presence of AgNPs. The FTIR spectra of AgNPs exhibited prominent peaks at the spectra showed sharp and strong absorption band at 3,406.71 to 3,431.90 cm^?1 double in case of NH₂ group of a primary amine (N–H stretch). The presence of the sharp peak at 2,926.54 to 2,925.80 cm^?1 very broad often looks like distorted baseline (O–H carboxylic acids). The band 1,633.26 to 1,625.81 cm^?1 was assigned to C?=?C alkenes, aromatic ring stretching vibration, respectively. SEM analysis of the synthesized AgNPs clearly showed the clustered and irregular shapes, mostly aggregated and having the size of 120 nm. TEM reveals spherical shape of synthesized AgNPs. Particle size analysis revealed that the size of particles ranges from 25 to 47 nm with average size of 34.61 nm. Energy-dispersive X-ray spectroscopy showed the complete chemical composition of the synthesized AgNPs. In larvicidal activity, the results showed that the maximum efficacy was observed in synthesized AgNPs against the fourth instar larvae of A. stephensi (LC₅₀?=?12.47 and 16.84 mg/mL and LC₉₀?=?36.33 and 68.62 mg/mL) on 48 and 72 h of exposure and against C. quinquefasciatus (LC₅₀?=?43.80 mg/mL and LC₉₀?=?120.54 mg/mL) on 72-h exposure, and aqueous extract showed 100 % mortality against A. stephensi and C. quinquefasciatus (LC₅₀?=?78.62 and 55.21 mg/mL and LC₉₀?=?184.85 and 112.72 mg/mL) on 72-h exposure at concentrations of 50 mg/mL, respectively. The AgNPs did not exhibit any noticeable toxicity on Poecilia reticulata after 24, 48, and 72 h of exposure. These results suggest that the synthesized AgNPs have the potential to be used as an ideal eco-friendly approach for the control of the A. stephensi and C. quinquefasciatus. This method is considered as a new approach to control vectors. Therefore, this study provides the first report on the mosquito larvicidal activity of V. rosea synthesized AgNPs against vectors.     

Acaricidal activity of synthesized titanium dioxide nanoparticles using Calotropis gigantea against Rhipicephalus microplus and Haemaphysalis bispinosa

ObjectiveTo assess the acaricidal activity of titanium dioxide nanoparticles (TiO₂ NPs) synthesized from flower aqueous extract of Calotropis gigantea(C. gigantea) against the larvae of Rhipicephalus (Boophilus) microplus [R. (B.) microplus] and the adult of Haemaphysalis bispinosa (H. bispinosa).MethodsThe lyophilized C. gigantea flower aqueous extract of 50 mg was added with 100 mL of TiO(OH)₂ (10 mM) and magnetically stirred for 6 h. Synthesized TiO₂ NPs were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), and Energy dispersive X-ray spectroscopy (EDX). The synthesised TiO₂ NPs were tested against the larvae of R. (B.) microplus and adult of H. bispinosa were exposed to filter paper impregnated method.ResultsXRD confirmed the crystalline nature of the nanoparticles with the mean size of 10.52 nm. The functional groups for synthesized TiO₂ NPs were 1 405.19, and 1 053.45 cm^?1 for -NH₂ bending, primary amines and amides and 1 053.84 and 1 078.45 cm^?1 for C-O. SEM micrographs of the synthesized TiO₂ NPs showed the aggregated and spherical in shape. The maximum efficacy was observed in the aqueous flower extract of C. gigantea and synthesized TiO₂ NPs against R. (B.) microplus (LC₅₀=24.63 and 5.43 mg/L and r²=0.960 and 0.988) and against H. bispinosa (LC₅₀= 35.22 and 9.15 mg/L and r² = 0.969 and 0.969), respectively.ConclusionsThe synthesized TiO₂ NPs were highly stable and had significant acaricidal activity against the larvae of R. (B.) microplus and adult of H. bispinosa. This study provides the first report of synthesized TiO₂ NPs and possessed excellent anti-parasitic activity.     

Daratumumab,bortezomib and dexamethasone at first relapse for patients with multiple myeloma: A real-world multicentre UK retrospective analysis

Daratumumab, bortezomib and dexamethasone (DVd) is approved for patients with relapsed multiple myeloma following the CASTOR phase 3 clinical trial. This retrospective multicentre analysis assesses the overall response rate (ORR) and progression-free survival (PFS) in routine clinical practice for patients at first relapse treated with DVd incorporating weekly bortezomib. Data were collected from 296 sequential patients treated across 15 UK centres. After a median follow-up of 21 months, the ORR was 82% (26% partial response, 56% very good partial response or better) and the median PFS was 16 months [95% confidence interval (CI) 12–20 months]. Results were similar regardless of prior lenalidomide exposure. The median time to next treatment was 20 months (95% CI 15–25 months) and the estimated overall survival at two years was 74%. Patients with high-risk features (by cytogenetics, International Staging System or extramedullary disease) and those treated within 18 months of initiation of progression-free treatment, or within 12 months of autologous stem cell transplant, had significantly inferior outcomes. The grade 2 and 3 peripheral neuropathy rate was 7%. DVd with weekly bortezomib was effective in a heterogenous real-world population at first relapse with a low rate of peripheral neuropathy. However, high-risk patients had inferior outcomes and should be considered for alternative treatments.     

Larvicidal and repellent activity of medicinal plant extracts from Eastern Ghats of South India against malaria and filariasis vectors

ObjectiveTo evaluate the larvicidal and repellent activities of ethyl acetate and methanol extracts of Acacia concinna (A. concinna), Cassia siamea (C. siamea), Coriandrum sativum (C. sativum),Cuminum cyminum (C. cyminum), Lantana camara (L. camara), Nelumbo nucifera (N. nucifera) Phyllanthus amarus (P. amarus), Piper nigrum (P. nigrum) and Trachyspermum ammi (T. ammi) against Anopheles stephensi (An. stephensi) and Culex quinquefasciatus (Cx. quinquefasciatus).MethodsThe larvicidal activity of medicinal plant extracts were tested against early fourth-instar larvae of malaria and filariasis vectors. The mortality was observed 24 h and 48 h after treatment, data were subjected to probit analysis to determine the lethal concentrations (LC₅₀ and LC₉₀) to kill 50 and 90 per cent of the treated larvae of the tested species. The repellent efficacy was determined against two mosquito species at five concentrations (31.25, 62.50, 125.00, 250.00, and 500.00 ppm) under the laboratory conditions.ResultsAll plant extracts showed moderate effects after 24 h and 48 h of exposure; however, the highest activity was observed after 24 h in the leaf methanol extract of N. nucifera, seed ethyl acetate and methanol extract of P. nigrum against the larvae of An. stephensi (LC₅₀ = 34.76, 24.54 and 30.20 ppm) and against Cx. quinquefasciatus (LC₅₀ = 37.49, 43.94 and 57.39 ppm), respectively. The toxic effect of leaf methanol extract of C. siamea, seed methanol extract of C. cyminum, leaf ethyl acetate extract of N. nucifera, leaf ethyl acetate and methanol extract of P. amarus and seed methanol extract of T. ammi were showed 100% mortality against An. stephensi and Cx. quinquefasciatus after 48 h exposer. The maximum repellent activity was observed at 500 ppm in methanol extracts of N. nucifera, ethyl acetate and methanol extract of P. nigrum and methanol extract of T. ammi and the mean complete protection time ranged from 30 to 150 min with the different extracts tested.ConclusionsThese results suggest that the leaf and seed extracts of C. siamea, N. nucifera, P. amarus, P. nigrum and T. ammi have the potential to be used as an ideal ecofriendly approach for the control of the An. stephensi and Cx. quinquefasciatus.     

Screening for feeding deterrent activity of herbal extracts against the larvae of malaria vector Anopheles subpictus Grassi

This no-choice, laboratory study focuses on the feeding of homogeneous powdered, dried, yeast with different plant extracts on mosquito fourth-instar larvae to determine the effects on their mortality. Screening for antifeedant activity of plant extracts with some known medicinal attributes could lead to the discovery of new agents for vector control. The aim of this study was to investigate the antifeedant activity of crude leaf hexane, ethyl acetate, acetone, and methanol extracts of Andrographis lineata Wallich ex Nees. (Acanthaceae), Anisomeles malabarica (L.) Sims. (Lamiaceae), Argemone mexicana L. (Papaveraceae), Aristolochia bracteolata Lam. (Aristolochiaceae), Chrysanthemum indium L. (Asteraceae), Datura metal L. (Solanaceae), Eclipta prostrata L. (Asteraceae), and Sesbania grandiflora (L.) Pers. (Fibaceae) against the fourth-instar larvae of Anopheles subpictus Grassi (Diptera:Culicidae). All the crude extracts showed antifeedant activity in a dose-dependent manner. The plant extracts exhibited a significant antifeedant activity after 24 and 48 h of exposure; however, the highest larval mortality was found in leaf ethyl acetate extract of A. malabarica, acetone extract E. prostrata, methanol extract of A. lineata, C. indium, and S. grandiflora after 24 h (LC₅₀ = 2.53, 2.82, 2.31, 2.56, and 2.08 mg/mL; LC₉₀ = 6.40, 8.06, 7.45, 6.98, and 6.20 mg/mL), respectively. The hexane extract of A. lineata, D. metal, methanol extract of A. bracteolata and E. prostrata showed larval mortality after 48 h (LC₅₀ = 3.05, 2.11, 3.00, and 2.18 mg/mL; LC₉₀ = 9.06, 6.22, 8.23, and 5.77 mg/mL), respectively. One hundred percent larval mortality was observed in methanol extract of A. lineata, and C. indium after 24 h and the hexane extract of A. lineata and D. metal after 48 h at 10 mg/100 mL. The methanol extracts of A. lineata and C. indium significantly increased larval mortality in comparison to larvae fed with untreated diet. Bacillus thuringiensis subsp. israelensis is widely accepted as a biological pesticide because of its highly specific activity against dipteran insects without adverse effects on other organisms. The feeding deterrent activity of different herbal extracts against the larvae of malaria vector A. subpictus exhibited significantly lower toxicity compare with the bio larvicides, B. thuringiensis. These results suggest that the methanol extract of A. lineata, C. indium, the hexane extract of A. lineata and D. metal have the potential to be used as an ideal eco-friendly approach for the control of the medically important vector A. subpictus. These findings corroborate traditional insecticidal application of selected plants and the results can be extended for the control of mosquitoes.     

Synthesis, NMR spectral studies and antimicrobial evaluation of some 2-(benzothiazol-2-yl)-1-(alkyl-2r,6c-diarylpiperidin-4-ylidine)hydrazine derivatives

Substituted 2-(benzothiazol-2-yl)-1-(alkyl-2,6-diarylpiperidin-4-ylidine)hydrazines 10–17 were synthesized by the condensation of different 2r,6c-diarylpiperidin-4-ones 1–8 with 2-hydrazinobenzothiazole 9. All the synthesized compounds were investigated in solution and in the solid state by IR, ¹H, ¹³C and 2D NMR spectral techniques. The structure–activity relationships were studied by the screening of the antimicrobial activity over a representative panel of bacterial and fungal strains using two-fold serial dilution method.