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1.
Saudi Pharm J ; 32(1): 101930, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38226351

RESUMO

Perampanel (PER), a novel 3rd-generation antiseizure drug that modulates altered post-synaptic glutamatergic storming by selectively inhibiting AMPA receptors, is recently approved to treat intractable forms of seizures. However, to date, presumably consequences of long-term PER therapy on the comorbid deleterious psychiatric disturbances and its correlation with neuroinflammatory parameters are not fully investigated in chronic models of epilepsy. Therefore, we investigated the real-time effect of PER on brain electroencephalographic (EEG) activity, behavioral alterations, redox balance, and relative mRNA expression in pentylenetetrazole (PTZ) induced kindling. Male BALB/c mice were pretreated with PER (0.125, 0.25, and 0.5 mg/kg) for 3 weeks and challenged with 11 injections of PTZ at the sub-threshold dose of 40 mg/kg every other day. vEEG from implanted cortical electrodes was monitored to elucidate seizure propagation and behavioral manifestations. Recorded EEG signals exhibited that PER 0.5 mg/kg pretreatment exceptionally impeded the onset of sharp epileptic spike-wave discharges and associated motor symptoms. Additionally, qEEG analysis showed that PER prevented alterations in absolute mean spectral power and reduced RMS amplitude of epileptogenic spikes vs PTZ control. Furthermore, our outcomes illustrated that PER dose-dependently attenuated PTZ-evoked anxiety-like behavior, memory deficits, and depressive-like behavior that was validated by a series of behavioral experiments. Moreover PER, significantly reduced lipid peroxidation, AChE, and increased levels of SOD and total thiol in the mice brain via AMPAR antagonism. Post-PTZ kindling provoked overstimulation of BDNF/TrkB signaling and increased release of pro-inflammatory cytokines that were reversed by PER with suppression of iNOS in brain immune cells. In conclusion, our findings highlight that PER might play an auspicious preventive role in the proepileptic transformation of brain circuits via suppression of BDNF/TrkB signaling and reduced transcriptional levels of neuroinflammatory markers leading to improvised epilepsy-induced neurobehavioral and neurochemical effects.

2.
Bull Environ Contam Toxicol ; 111(1): 14, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37450051

RESUMO

The current study assessed the harmful effects of Atrazine (ATZ) herbicide on haematology and biochemistry of the freshwater fish Ctenopharyngodon idella, a commercially significant fish in Pakistan. C. idella (13 ± 8.4 cm; 132 ± 5.6 g) was exposed to graded levels of ATZ, and its 96-hour LC50 value at 25°C was calculated to be 150.5 µl/L. After exposure to ATZ, fish displayed rapid movements, a loss of balance in position and equilibrium, anxious swimming patterns, colour changes, and increased mucous production. The MCHC, MCH, RBCs, and Hb in C. idella decreased significantly (P < 0.05), whereas the MCV, Ht, and WBCs were significantly increased (P < 0.05). At different time intervals (24, 48, 72, and 96 h) following ATZ administration (50, 100, 150, and 200 µl/L), biochemical analysis significantly decreased (P < 0.05) triglyceride, total protein, cholesterol, and albumin levels, whereas glucose levels significantly increased (P < 0.05). We concluded that ATZ is toxic to C. idella, altering their haematology and blood biochemistry even after only a brief exposure.


Assuntos
Atrazina , Carpas , Doenças dos Peixes , Hematologia , Herbicidas , Animais , Atrazina/toxicidade , Imunidade Inata , Carpas/metabolismo , Herbicidas/toxicidade , Herbicidas/análise , Proteínas de Peixes/metabolismo , Ração Animal/análise
3.
Saudi Pharm J ; 31(1): 96-109, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36685303

RESUMO

Honey bee venom (BV) is a valuable product, and has a wide range of biological effects, and its use is rapidly increasing in apitherapy. Therefore, the current study, we reviewed the existing knowledge about BV composition and its numerous pharmacological properties for future research and use. Honey bee venom or apitoxin is produced in the venom gland in the honey bee abdomen. Adult bees use it as a primary colony defense mechanism. It is composed of many biologically active substances including peptides, enzymes, amines, amino acids, phospholipids, minerals, carbohydrates as well as some volatile components. Melittin and phospholipase A2 are the most important components of BV, having anti-cancer, antimicrobial, anti-inflammatory, anti-arthritis, anti-nociceptive and other curative potentials. Therefore, in medicine, BV has been used for centuries against different diseases like arthritis, rheumatism, back pain, and various inflammatory infections. Nowadays, BV or its components separately, are used for the treatment of various diseases in different countries as a natural medicine with limited side effects. Consequently, scientists as well as several pharmaceutical companies are trying to get a new understanding about BV, its substances and its activity for more effective use of this natural remedy in modern medicine.

4.
Saudi Pharm J ; 31(2): 191-206, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36942273

RESUMO

Introduction: Ailanthus altissima is an indigenous plant known for various remedial properties. The present study aimed to evaluate the neuroprotective potential of methanolic extract Ailanthus altissima (AA) bark as current scientific trend is searching plant for neurodegenerative diseases, worldwide. Methodology: In in-vitro experiments, the AA was analyzed for phenols, flavonoids, antioxidative and cholinesterase inhibitory properties with subsequent detailed characterization for secondary metabolites. The in-vivo neurological effects were evaluated in rats through behavioral assessment for anxiety and memory after chronic administration (28 days) of 50-200 mg/kg of AA. At the end of behavior studies, isolated brains were biochemically tested to determine antioxidant enzyme activity. Results: AA was found rich in phenols/flavonoids and active in radical scavenging with the presence of 13 secondary metabolites in UHPLC-MS analysis. The AA yielded anxiolytic effects dose-dependently in the open field, light/dark and elevated-plus maze tests as animals significantly (P < 0.05 vs control group) preferred open arena, illuminated zone and exposed arms of maze. Similarly, the animals treated with AA showed significant (P < 0.05 vs amnesic group) increase in spontaneous alternation, discrimination index in y-maze, novel object recognition tests. Further, AA.Cr treated rats showed noticeably shorter escape latencies in Morris water maze tests.In biochemical analysis, the dissected brains AA treated rats showed reduced levels of AChE and malondialdehyde with increased levels of first-line antioxidant enzymes i.e. glutathione peroxidase and superoxide dismutase. These observed biological effects might be attributed to phenols and flavonoids constituents owned by AA. -The in-silico studies showed thatconessine and lophirone J phytocompounds have good blood-brain barrier permeability and interaction with AChE. Conclusion: The outcomes of this study validate that bark of Ailanthus altissima might work as a source of bioactive phytochemicals of neuroprotective potential.

5.
Saudi Pharm J ; 30(5): 494-507, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35693436

RESUMO

Introduction: The pentylenetetrazol (PTZ)-induced kindling model acts through the antagonism of central GABAA receptors and is one of the most widely used experimental animal models to study the characteristics of seizure development, behavioral manifestations and evaluation of antiseizure effects of existing and new drug candidates. Methodology: In the current study, we investigated the impact of chronically administered levetiracetam (50 mg/kg) and sodium selenite (Sod.Se: 0.25 and 0.5 mg/kg) alone and in combination during the kindling process (21 days) in rats. Moreover, the behavioral changes (through the integration of a wide array of behavioral tests) and markers of oxidative stress in isolated brain homogenates were assessed in PTZ- kindled rats. Results: The outcomes from the fully kindled rats revealed the increased seizure score and severity over time with marked behavioral deficits. However, the animals treated with the selected dose of LEV alone showed partial protection from epileptogenesis and amelioration (P < 0.05) of anxiety-like behavior (open filed, light/dark, elevated plus maze tests), cognitive impairment (y-maze, novel object recognition and water maze tests) and depression (sucrose preference test). Moreover, combining the LEV with sodium selenite resulted in a significant neuroprotective effect in comparison to monotherapy by reducing the disease progression and ameliorating behavioral outcomes. The combination of Sod.Se in a dose-dependent manner with LEV produced additive effects as maximum animals remained seizure-free compared to kindled rats (P < 0.05). The attenuation of PTZ induced oxidative stress was evident from the reduced malondialdehyde and elevated superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) level with P < 0.05, as compared to control epileptic rats. These observed results of combination therapy might be due to the antioxidant and neuroprotective properties of Sod.Se, thus augmenting the seizure-modifying potentials of levetiracetam. Conclusion: Overall, the current findings support the prominence of combining the Sod.Se with LEV, over monotherapy to deal with prevailing challenges of drug resistance and neuropsychiatric sufferings common in epileptic patients.

6.
Pak J Pharm Sci ; 33(2(Supplementary)): 815-820, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32863256

RESUMO

Red kidney beans have antioxidant effect and thereby can help in skin smoothening, moisturizing, whitening and have anti-wrinkles effect. The study was based on the formulation of a stable w/o emulsion possessing extract of Phaseolus vulgaris L. seeds, using paraffin oil with the aim to investigate its effect on various skin parameters. The extract, achieved by concentrating ethanolic extract of red kidney beans was embedded in the internal aqueous part of w/o emulsion. An active formulation possessing concentrated extract of red kidney beans and a placebo formulation having no active material in the aqueous phase were formulated and placed at various conditions for the duration of 28 days, to observe the stability of cream. The placebo and formulation were stable at different storage conditions in terms of phase separation and colour changes. Minute liquefaction was observed from 21stday up to 28th day in formulations which were kept at 40°C +75% RH (relative humidity). With the passage of time significant changes were observed in formulation pH while insignificant changes were observed at basic pH. Different effects of creams i.e., placebo and formulations were observed on the human skin by applying them on the volunteer's cheeks for about 8 weeks. A stable w/o emulsion can be formulated by using red kidney beans' extract without any phase separation, liquefaction and colour change over 28 days storage.


Assuntos
Pomadas/farmacologia , Phaseolus/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Adulto , Antioxidantes/farmacologia , Química Farmacêutica/métodos , Estabilidade de Medicamentos , Emulsões/farmacologia , Humanos , Umidade , Concentração de Íons de Hidrogênio , Masculino , Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Temperatura
7.
J Pak Med Assoc ; 69(8): 959-963, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31431775

RESUMO

The present study was conducted to estimate the prevalence of rubella infection in pregnant women of district Lakki Marwat leading to foetal death, abortion, premature birth or congenital rubella syndrome. A total of 200 blood samples were collected from pregnant women visiting different maternal health care centers of the study area. Sera samples were tested for rubella-specific IgG and IgM antibodies through ELISA. The overall sero-positivity rate for IgG was 16% and for IgM was 2.5% in the pregnant women respectively. A higher sero-positivity rate was observed in the age group of 26-33 years. Women of rural areas showed higher sero-positivity rate than urban areas. The high sero-prevalence of rubella in the pregnant women of the study area poses a serious threat to the developing foetus.


Assuntos
Complicações Infecciosas na Gravidez/epidemiologia , Rubéola (Sarampo Alemão)/epidemiologia , Aborto Espontâneo , Adolescente , Adulto , Distribuição por Idade , Anticorpos Antivirais/imunologia , Status Econômico , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Paquistão/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Nascimento Prematuro , Rubéola (Sarampo Alemão)/imunologia , Síndrome da Rubéola Congênita , Estudos Soroepidemiológicos , Natimorto , Adulto Jovem
8.
Epilepsy Behav ; 88: 189-204, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30292054

RESUMO

Intracerebral infection of C57BL/6 mice with Theiler's murine encephalomyelitis virus (TMEV) replicates many features of viral encephalitis-induced epilepsy in humans, including neuroinflammation, early (insult-associated) and late (spontaneous) seizures, neurodegeneration in the hippocampus, and cognitive and behavioral alterations. Thus, this model may be ideally suited to study mechanisms involved in encephalitis-induced epilepsy as potential targets for epilepsy prevention. However, spontaneous recurrent seizures (SRS) occur too infrequently to be useful as a biomarker of epilepsy, e.g., for drug studies. This prompted us to evaluate whether epileptiform spikes or spike clusters in the cortical electroencephalogram (EEG) may be a useful surrogate of epilepsy in this model. For this purpose, we developed an algorithm that allows efficient and large-scale EEG analysis of early and late seizures, spikes, and spike clusters in the EEG. While 77% of the infected mice exhibited early seizures, late seizures were only observed in 33% of the animals. The clinical characteristics of early and late seizures did not differ except that late generalized convulsive (stage 5) seizures were significantly longer than early stage 5 seizures. Furthermore, the frequency of SRS was much lower than the frequency of early seizures. Continuous (24/7) video-EEG monitoring over several months following infection indicated that the latent period to onset of SRS was 61 (range 16-91) days. Spike and spike clusters were significantly more frequent in infected mice with late seizures than in infected mice without seizures or in mock-infected sham controls. Based on the results of this study, increases in EEG spikes and spike clusters in groups of infected mice may be used as a new readout for studies on antiepileptogenic or disease-modifying drug effects in this model, because the significant increase in average spike counts in mice with late seizures obviously indicates a proepileptogenic alteration.


Assuntos
Eletroencefalografia , Encefalite Viral/complicações , Epilepsia/diagnóstico , Convulsões/diagnóstico , Theilovirus , Algoritmos , Animais , Modelos Animais de Doenças , Epilepsia/fisiopatologia , Epilepsia/virologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Convulsões/fisiopatologia , Convulsões/virologia
9.
Molecules ; 21(8)2016 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-27472315

RESUMO

Camptothecin (CPT) has anticancer, antiviral, and antifungal properties. However, there is a dearth of information about antibacterial activity of CPT. Therefore, in this study, we investigated the inhibitory effect of CPT on Acidovorax avenae subsp. avenae strain RS-2, the pathogen of rice bacterial brown stripe, by measuring cell growth, DNA damage, cell membrane integrity, the expression of secretion systems, and topoisomerase-related genes, as well as the secretion of effector protein Hcp. Results indicated that CPT solutions at 0.05, 0.25, and 0.50 mg/mL inhibited the growth of strain RS-2 in vitro, while the inhibitory efficiency increased with an increase in CPT concentration, pH, and incubation time. Furthermore, CPT treatment affected bacterial growth and replication by causing membrane damage, which was evidenced by transmission electron microscopic observation and live/dead cell staining. In addition, quantitative real-time PCR analysis indicated that CPT treatment caused differential expression of eight secretion system-related genes and one topoisomerase-related gene, while the up-regulated expression of hcp could be justified by the increased secretion of Hcp based on the ELISA test. Overall, this study indicated that CPT has the potential to control the bacterial brown stripe pathogen of rice.


Assuntos
Antibacterianos/farmacologia , Camptotecina/farmacologia , Comamonadaceae/crescimento & desenvolvimento , Oryza/microbiologia , Doenças das Plantas/prevenção & controle , Proteínas de Bactérias/genética , Membrana Celular/efeitos dos fármacos , Comamonadaceae/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Doenças das Plantas/microbiologia
11.
Int J Mol Sci ; 16(12): 28050-62, 2015 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-26602922

RESUMO

Biofilm formation is important for virulence of a large number of plant pathogenic bacteria. Indeed, some virulence genes have been found to be involved in the formation of biofilm in bacterial fruit blotch pathogen Acidovorax citrulli. However, some virulent strains of A. citrulli were unable to format biofilm, indicating the complexity between biofilm formation and virulence. In this study, virulence-related genes were identified in the biofilm-defective strain A1 of A. citrulli by using Tn5 insertion, pathogenicity test, and high-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR). Results from this study indicated that 22 out of the obtained 301 mutants significantly decreased the virulence of strain A1 compared to the wild-type. Furthermore, sequence analysis indicated that the obtained 22 mutants were due to the insertion of Tn5 into eight genes, including Aave 4244 (cation diffusion facilitator family transporter), Aave 4286 (hypothetical protein), Aave 4189 (alpha/beta hydrolase fold), Aave 1911 (IMP dehydrogenase/GMP reductase domain), Aave 4383 (bacterial export proteins, family 1), Aave 4256 (Hsp70 protein), Aave 0003 (histidine kinase, DNA gyrase B, and HSP90-like ATPase), and Aave 2428 (pyridoxal-phosphate dependent enzyme). Furthermore, the growth of mutant Aave 2428 was unaffected and even increased by the change in incubation temperature, NaCl concentration and the pH of the LB broth, indicating that this gene may be directly involved in the bacterial virulence. Overall, the determination of the eight pathogenicity-related genes in strain A1 will be helpful to elucidate the pathogenesis of biofilm-defective A. citrulli.


Assuntos
Biofilmes , Comamonadaceae/genética , Comamonadaceae/patogenicidade , Elementos de DNA Transponíveis , Mutagênese , Virulência/genética , Sequência de Aminoácidos , Biologia Computacional/métodos , Genes Bacterianos , Dados de Sequência Molecular , Mutagênese Insercional , Mutação , Alinhamento de Sequência , Estresse Fisiológico
12.
Front Nutr ; 11: 1371672, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38899322

RESUMO

Pollen grains are the male reproductive part of the flowering plants. It is collected by forager honey bees and mixed with their salivary secretions, enzymes, and nectar, which form fermented pollen or "bee bread" which is stored in cells of wax honeycombs. Bee pollen (BP) is a valuable apitherapeutic product and is considered a nutritional healthy food appreciated by natural medicine from ancient times. Recently, BP has been considered a beneficial food supplement and a value-added product that contains approximately 250 different bioactive components. It contains numerous beneficial elements such as Mg, Ca, Mn, K, and phenolic compounds. BP possesses strong antioxidant, anti-inflammatory, antimicrobial, antiviral, analgesic, immunostimulant, neuroprotective, anti-cancer, and hepatoprotective properties. It is used for different purposes for the welfare of mankind. Additionally, there is a growing interest in honey bee products harvesting and utilizing for many purposes as a natural remedy and nutritive function. In this review, the impacts of BP on different organisms in different ways by highlighting its apitherapeutic efficacy are described.

13.
Biomed Pharmacother ; 175: 116791, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38776672

RESUMO

Epilepsy is an abiding condition associated with recurrent seizure attacks along with associated neurological and psychological emanation owing to disparity of excitatory and inhibitory neurotransmission. The current study encompasses the assessment of the Nyctanthes arbor-tristis L. methanolic extract (Na.Cr) in the management of convulsive state and concomitant conditions owing to epilepsy. The latency of seizure incidence was assessed using pentylenetetrazol (PTZ) kindling models along with EEG in Na.Cr pretreated mice, trailed by behavior assessment (anxiety and memory), biochemical assay, histopathological alterations, chemical profiling through GCMS, and molecular docking. The chronic assessment of PTZ-induced kindled mice depicted salvation in a dose-related pattern and outcomes were noticeable with extract at 400 mg/kg. The extract at 400 mg/kg defends the progress of kindling seizures and associated EEG. Co-morbid conditions in mice emanating owing to epileptic outbreaks were validated by behavioral testing and the outcome depicted a noticeable defense related to anxiety (P<0.001) and cognitive deficit (P<0.001) at 400 mg/kg. The isolated brains were evaluated for oxidative stress and the outcome demonstrated a noticeable effect in a dose-dependent pattern. Treatment with Na.Cr. also preserved the brain from PTZ induced neuronal damage as indicated by histopathological analysis. Furthermore, the GCMS outcome predicted 28 compounds abundantly found in the plant. The results congregated in the current experiments deliver valued evidence about the defensive response apportioned by Na.Cr which might be due to decline in oxidative stress, AChE level, and GABAergic modulation. These activities may contribute to fundamental pharmacology and elucidate some mechanisms behind the activities of Nyctanthes arbor-tristis.


Assuntos
Anticonvulsivantes , Eletroencefalografia , Excitação Neurológica , Pentilenotetrazol , Extratos Vegetais , Convulsões , Animais , Excitação Neurológica/efeitos dos fármacos , Camundongos , Extratos Vegetais/farmacologia , Masculino , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Anticonvulsivantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Simulação de Acoplamento Molecular , Simulação por Computador , Modelos Animais de Doenças , Estresse Oxidativo/efeitos dos fármacos , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico
14.
Eur J Pharmacol ; 978: 176792, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38950834

RESUMO

The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining. Results revealed that acute electrophysiological (EEG) profiling of the ASD cocktail markedly halted sharp ictogenic spikes as well as altered dynamics of brain wave oscillations thus validating the need for polytherapy vs. monotherapy. In TLE animals, pharmacological intervention for 6 weeks with topiramate 10 mg/kg in combination with PREG and LAC at the dose of 20 mg/kg exhibited marked protection from SRS incidence, improved body weight, offensive aggression, anxiety-like behavior, cognitive impairments, and depressive-like behavior (p < 0.05). Moreover, combination therapy impeded redox impairments as evidenced by decreased MDA and AchE levels and increased activity of antioxidant SOD, GSH enzymes. Furthermore, polytherapy rescued animals from SE-induced neurodegeneration with increased neuronal density in CA1, CA3c, CA3ab, hilus, and granular cell layer (GCL) of the dentate gyrus. In conclusion, early polytherapy with topiramate in combination with pregabalin and lacosamide prompted synergy and prevented epileptogenesis with associated psychological and neuropathologic alterations.


Assuntos
Modelos Animais de Doenças , Eletroencefalografia , Lacosamida , Fármacos Neuroprotetores , Pregabalina , Topiramato , Animais , Lacosamida/farmacologia , Lacosamida/uso terapêutico , Topiramato/farmacologia , Topiramato/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Masculino , Pregabalina/farmacologia , Pregabalina/uso terapêutico , Ratos , Comportamento Animal/efeitos dos fármacos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Quimioterapia Combinada , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Hipocampo/patologia , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/fisiopatologia , Ratos Wistar , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/induzido quimicamente
15.
ACS Omega ; 9(24): 26004-26019, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38911714

RESUMO

Pentylenetetrazole (PTZ)-induced kindling is a broadly used experimental model to study the anticonvulsive potential of new and existing chemical moieties with the aim of discovering drugs hindering seizure progression and associated neurological comorbidities. In the present study, the impact of brivaracetam (BRV) (10 and 20 mg/kg) as monotherapy as well as in combination with 0.25 mg/kg of perampanel (PRP) was investigated on seizure progression with simultaneous electroencephalographic changes in PTZ kindling mouse model. Subsequently, mice were experimentally analyzed for anxiety, cognition, and depression after which their brains were biochemically evaluated for oxidative stress. The outcomes demonstrated that BRV alone delayed the kindling process, but BRV + PRP combination significantly (p < 0.0001) protected the mice from seizures of higher severity and demonstrated an antikindling effect. The PTZ-kindled mice exhibited anxiety, memory impairment, and depression in behavioral tests, which were remarkably less (p < 0.001) in animals treated with drug combination (in a dose-dependent manner) as these mice explored central, illuminated, and exposed zones of open-field test, light/dark box, and elevated plus maze. Moreover, memory impairment was demonstrated by kindled mice, which was significantly (p < 0.001) protected by BRV + PRP as animal's spontaneous alteration, object discrimination, and step-through latencies were increased in various tests employed for the assessment of cognitive abilities. The brains of PTZ-kindled mice had increased malondialdehyde and reduced antioxidant enzymes while treatment with BRV + PRP combination prevented kindling-induced elevation in oxidative markers. The outcomes of this study demonstrate that combining the PRP at low dose augmented the antiseizure properties of BRV as both drugs when administered simultaneously hindered the process of kindling by reducing PTZ-induced excessive electrical activity and oxidative stress in the brain.

16.
Biomed Pharmacother ; 170: 115935, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38101280

RESUMO

Chemical kindling is broadly used experimental model to investigate novel treatments on the process of epileptogenesis and coexisting behavioral comorbidities. The current study aimed to investigate the low dose perampanel (PER) (0.125 and 0.5 mg/kg) and pregabalin (PG) (15 mg/kg) as standalone treatments and in combination on kindling-induced seizure progression with concurrent electroencephalographic alterations. Mice were subjected to pentylenetetrazole (PTZ)-induced kindling followed by neurobehavioral assessment for anxiety-like activity and cognitive deficit through behavioral experiments. The monotherapy with PER at 0.5 mg/kg and PG at 15 mg/kg delayed the kindling process but PRP+PG yielded pronounced benefits and hindered the development of seizures of higher severity. PER+PG combination relieved the animals from anxiety-like behavior in various employed anxiogenic tests. Furthermore, the kindling-associated cognitive deficit was protected by PER+PG combination as increased alteration behavior, discrimination index and latencies to enter the dark zone were noted in y-maze, object recognition and passive avoidance tests, respectively while shorter escape latencies were noted in water maze. The brain samples of kindled mice had elevated malondialdehyde and reduced catalase, superoxide dismutase and glutathione peroxidase enzymes while treatment with PER and PG combination shielded the mice from heightened kindling-associated oxidative stress. Overall, the findings of the present study illustrate that concurrent administration of PER and PG effectively hindered the process of epileptogenesis by protecting neuronal excitability and brain oxidative stress. The results predict the dominance of PER and PG combination over monotherapy which might serve as an effective novel combination to combat drug resistance and behavioral disorders in epileptic patients.


Assuntos
Epilepsia , Excitação Neurológica , Humanos , Camundongos , Animais , Pentilenotetrazol/farmacologia , Pregabalina/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Epilepsia/tratamento farmacológico , Estresse Oxidativo , Anticonvulsivantes/efeitos adversos
17.
Gels ; 9(7)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37504443

RESUMO

Gelatin-based hydrogels have shown good injectability and biocompatibility and have been broadly used for drug delivery and tissue regeneration. However, their low mechanical strengths and fast degradation rates must be modified for long-term implantation applications. With an aim to develop mechanically stable hydrogels, reactive anhydride-based oligomers were developed and used to fabricate gelatin-based crosslinked hydrogels in this study. A cascade of hydrophilic oligomers containing reactive anhydride groups was synthesized by free radical polymerization. These oligomers varied in degree of reactivity, comonomer composition, and showed low molecular weights (Mn < 5 kDa). The reactive oligomers were utilized to fabricate hydrogels that differed in their mechanical strengths and degradation profiles. These formulations exhibited good cytocompatibility with human adipose tissue-derived stem cells (hADCs). In conclusion, the reactive MA-containing oligomers were successfully synthesized and utilized for the development of oligomer-crosslinked hydrogels. Such oligomer-crosslinked gelatin-based hydrogels hold promise as drug or cell carriers in various biomedical applications.

18.
Appl Biochem Biotechnol ; 195(1): 264-282, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36074235

RESUMO

Physical and chemical methods for production of nanoparticles (NPs) are not only harmful for environment but also toxic for living organism. The present study attempts to synthesize ZnO NPs using the natural plant extract of Fagonia cretica. The phytochemical screening of F. cretica water extract was performed to check the presence of biologically active compounds like alkaloids, tannins, carbohydrates, proteins, phenols, saponins, flavonoids, and steroids. Well-prepared ZnO NPs given sharp absorption peak at 362 were confirmed by UV-visible. XRD analysis showed the ZnO NPs having wurtzite hexagonal structure with crystalline form. TEM analysis endorses flower-shaped ZnO nanoparticles ~ 100-1000 nm. FTIR spectrum suggested the involvement of phenolic groups and amino acids and amide linkages in protein performs as the stabilizing agent in the synthesis of ZnO NPs. The ZnO NPs showed strong antibacterial behavior against two bacterial strains Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli. In addition, ZnO NPs exhibited strong antioxidant activity of 79%:85.6%:89.9% at 5 µg/mL:10 µg/mL:5 µg/mL concentration of ZnO NPs respectively. This work indicates that Fagonia is considered to be appropriate and promising candidate for extending the innovative applications in the field of medicine and industry and also helpful and useful to the scientific communities.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Óxido de Zinco/química , Nanopartículas/química , Bactérias/metabolismo , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Extratos Vegetais/química , Antibacterianos/química , Testes de Sensibilidade Microbiana , Nanopartículas Metálicas/química , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Front Public Health ; 11: 1084667, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36891337

RESUMO

Background: Correct medicine dosing is an important component in the safe and effective delivery of medicines, particularly for the pediatric population. However, there is a scarcity of public campaigns on the correct administration and choice of dosing aids for oral liquid dosage form in many countries, leading to medicine safety issues and therapeutic failures. Methods: The study targeted the assessment of the knowledge and practice of university students. It utilizes pre- and post-intervention surveys administered through google forms as a survey tool during online zoom and in-person sessions. The intervention included a short video presentation detailing the selection and use of medicine spoons and other aids for the administration of oral liquid dosage. The Fischer Exact test was used to assess the pre- and post-test shift of responses. Results: Nine-degree programs were engaged in the activity, and 108 students attended this health awareness activity after obtaining formal consent. A significant decline (CI = 95%, **** p-value < 0.05) in the choice of selecting tablespoon and a shift to a low-volume spoon, as well as rejection of an entire variety of household spoons, were observed. A significant improvement in the correct naming of spoons, the meaning of the abbreviation "tsp," and the correct volume of a standard teaspoon were also observed with a p-value of <0.001. Conclusion: A deficit in the knowledge of the proper use of measuring devices for oral liquid medicines in the educated population was observed, which can be enhanced through simple tools like short video presentations and awareness seminars.


Assuntos
Erros de Medicação , Estudantes , Humanos , Criança , Administração Oral , Preparações Farmacêuticas , Inquéritos e Questionários
20.
J Biotechnol ; 365: 1-10, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36708999

RESUMO

Herein, silver and zinc oxide Nanoparticles (NPs) were synthesized by using W. coagulant fruit extract as reducing agent and capping agent. The green synthesized NP with distinct properties were used for novel application against fungal and bacterial pathogen of honey bee (A. mellifera). The UV-spectroscopy confirms the synthesis of silver and zinc oxide NPs at 420 nm and 350 nm respectively. Further, XRD evaluated the monoclinic structure of Ag NPs while ZnO NPs showed wurtzite hexagonalcrystlized structure. Resistant honey bee pathogens such Paenibacilluslarvae, Melissococcus plutonius and Ascosphaera apis were isolated, identified and cultured in vitro to assess the antimicrobial potentials of Ag and ZnO NPs. Additionally, different biomolecules provide access to achieve maximum and stable Ag and ZnO NPs. It was also observed that with increasing the concentration of zinc oxide NPs and sliver NPs, zone of inhibition was also increased. Thus, present findings show that plant extracts can be a useful natural resource to prepare functional nonmaterial for targeted applications especially in the field of apicultural research.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Óxido de Zinco , Abelhas , Animais , Zinco/farmacologia , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Antibacterianos/farmacologia , Antibacterianos/química , Prata/farmacologia , Prata/química , Anti-Infecciosos/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana
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