Neuroprotective potential of topiramate, pregabalin and lacosamide combination in a rat model of acute SE and intractable epilepsy: perspectives from electroencephalographic, neurobehavioral and regional degenerative analysis.

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.

Bee pollen as a food and feed supplement and a therapeutic remedy: recent trends in nanotechnology.

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.

Neuroprotective Effect of Brivaracetam and Perampanel Combination on Electrographic Seizures and Behavior Anomalies in Pentylenetetrazole-Kindled Mice.

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.

Ameliorative effect of Nyctanthes arbor-tristis L. by suppression of pentylenetetrazole-induced kindling in mice: An insight from EEG, neurobehavioral and in-silico studies.

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.

Perampanel increases seizure threshold in pentylenetetrazole-kindled mice and improves behavioral dysfunctions by modifying mRNA expression levels of BDNF/TrkB and inflammatory markers.

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.

Unveiling the potential of perampanel and pregabalin in addressing pentylenetetrazole-induced electrographic alterations and neurobehavioral anomalies.

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.

Evaluation of anti-inflammatory and immunomodulatory potential of Lawsone (2-hydroxy-1,4-naphthoquinone) using pre-clinical rodent model of rheumatoid arthritis.

Background: Lawsone (2-hydroxy-1,4-naphthoquinone) is naturally present in Lawsonia Inermis and flowers of Eicchornia crassipes. This study assessed the anti-arthritic potential of Lawsone, using FCA-induced Sprague-Dawley rats. Methods: Arthritic progress was analyzed through a macroscopic scoring scale, measurement of paw edema, and histopathological changes. Effects of Lawsone on mRNA expression levels of inflammatory markers were examined using the reverse transcription PCR technique. ELISA technique was used to evaluate the PGE2 levels. Moreover, levels of biochemical and hematological parameters were also analyzed. Results: The research elucidated that Lawsone showed an inhibitory potential towards arthritic progress and ameliorated the paw edema. The histopathological analysis also validated the inhibition in arthritic development. Treatment with Lawosne reduced the expression levels of inflammatory markers in rats i.e., VEGF, TNF-α, MMP-2, MMP-3, NF-κB, IL-1ß, and IL-6. PGE2 levels (all p < 0.001) were also found reduced in treatment groups. Lab investigations showed improved results of hematological and hepatic parameters in the treated groups as compared to the positive control. This study found no hepatotoxic or nephrotoxic effects of Lawsone in the test doses. Conclusion: Lawsone possesses an anti-arthritic property which could be ascribed to its immunomodulatory and anti-inflammatory effects.

Novel Hydrophilic Oligomer-Crosslinked Gelatin-Based Hydrogels for Biomedical Applications.

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.

Variations in the Behaviour, Survival, Haematology, and Biochemistry of Ctenopharyngodon idella (Grass Carp) After Exposure to Commercial Grade Atrazine.

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.

Correct administration aid for oral liquid medicines: Is a household spoon the right choice?

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.

Effects of long-term Ailanthus altissima extract supplementation on fear, cognition and brain antioxidant levels.

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.

Tiagabine suppresses pentylenetetrazole-induced seizures in mice and improves behavioral and cognitive parameters by modulating BDNF/TrkB expression and neuroinflammatory markers.

Tiagabine (Tia), a new-generation antiseizure drug that mimics the GABAergic signaling by inhibiting GABA transporter type-1, is the least studied molecule in chronic epilepsy models with comorbid neurobehavioral and neuroinflammatory parameters. Therefore, the current study investigated the effects of Tia in a real-time manner on electroencephalographic (EEG) activity, behavioral manifestations and mRNA expression in pentylenetetrazole (PTZ)-kindled mice. Male BALB/c mice were treated with tiagabine (0.5, 1 and 2 mg/kg) for 21 days with simultaneous PTZ (40 mg/kg) injection every other day for a total of 11 injections and monitored for seizure progression with synchronized validation through EEG recordings from cortical electrodes. The post-kindling protection from anxiety and memory deficit was verified by a battery of behavioral experiments. Isolated brains were evaluated for oxidative alterations and real-time changes in mRNA expression for BDNF/TrkB, GAT-1 and GAT-3 as well as neuroinflammatory markers. Experimental results revealed that Tia at the dose of 2 mg/kg maximally inhibited the development of full bloom seizure and reduced epileptic spike discharges from the cortex. Furthermore, Tia dose-dependently exerted the anxiolytic effects and protected from PTZ-evoked cognitive impairment. Tia reduced lipid peroxidation and increased superoxide dismutase and glutathione levels in the brain via augmentation of GABAergic modulation. PTZ-induced upregulated BDNF/TrkB signaling and pro-inflammatory cytokines were mitigated by Tia with upregulation of GAT-1 and GAT-3 transporters in whole brains. In conclusion, the observed effects of Tia might have resulted from reduced oxidative stress, BDNF/TrkB modulation and mitigated neuroinflammatory markers expression leading to reduced epileptogenesis and improved epilepsy-related neuropsychiatric effects.

Pharmacological properties and therapeutic potential of honey bee venom.

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.

Nano-managing silver and zinc as bio-conservational approach against pathogens of the honey bee.

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.

Casting Zinc Oxide Nanoparticles Using Fagonia Blend Microbial Arrest.

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.

Availability of Access, Watch, and Reserve groups of essential antibiotics: a cross-sectional survey.

Background: Lower-middle income countries face drastic challenges in Access to essential medicines. Data regarding Pakistan is scarce with no comprehensive study in this regard. The objectives of the study are to document and compare public and private sector availability of all essential antibiotics as well as to conduct a comparison among the AWaRe groups. Methods: The study analyzed 103 essential antibiotics comprising 51 Access, 29 Watch, 6 Reserve, and 17 anti-tuberculosis drugs from 15th August to 10th September 2020 in Lahore, Pakistan. It included on-spot physical availability and availability trend surveys. The survey sites included five public tertiary care hospitals with one as anchor and four randomly selected. Their hospital pharmacies and one randomly selected private retail pharmacy from the vicinity each hospital comprised the ten sampling sites. Percentage availability for each antibiotic was categorized as high (>80%), fairly high (50-80%), low (30-<50%), very low (<30->0%), and not available (0%). Results: The mean percentage on-spot availability was 23.76% ± 5.19 (14-25%) for public facilities and 59.20% ± 4.45 (54-66%) for private sector retail pharmacies. The overall percentage of available essential antibiotics varied significantly (p** < 0.001) in public and private sector sampling sites. Except for the Watch group, all other groups showed the mode of 0% availability. A significant difference (p**** < 0.00001) was seen in percentage availability by Access, Watch, Reserve, and anti-TB-all groups of essential antibiotics. The availability trend survey revealed a list of 18 medicines as 'as never been available', and five medicines were 'not available for 5 years or more than 5 years.' Fourteen medicines as 'never been heard.' Conclusion: Non-availability of essential medicines is a significant public health challenge at public-sector facilities in Pakistan. It was observed that a number of essential antibiotics were not available in both public and private sectors. A number of corrective strategies are required. This includes the engagement of stakeholder and government bodies. This can help to improve supply chain barriers.

Crest to Trough Cellular Drifting of Green-Synthesized Zinc Oxide and Silver Nanoparticles.

Green nanotechnology facilitates the blooming of zinc oxide (ZnO) and silver (Ag) nanoparticles (NPs) with distinct flowerlike and spherical morphologies, respectively. The well-characterized NPs with an average size of 35 nm (ZnO) and 25 nm (Ag) were functionalized on the cresty plates for antibacterial inhibition against Staphylococcus aureus and Pseudomonas aeruginosa, with the flowerlike ZnONPs exhibiting 90.9% inhibition and AgNPs exhibiting 100% inhibition. Further, the in vivo underwater troughs for hematological, immunological, and serological analysis in Labeo rohita exhibited 102 > 575 > 104 and 206 > 109 > 81% at concentrations of 1, 2, and 3 mg/L with 4-day and 15-day treatment, respectively, over ZnONPs. However, AgNPs exhibited 257 > 408 > 124 and 86 > 202 > 43% with 4-day and 15-day treatment, respectively, at the same concentrations. The classical ZnNPs and AgNPs exhibited excellent inhibition potential and significant transfiguration of hematological, enzymological, and protein parameters as safe nanomedicine, but ZnONPs were found to be 58, 69, 29 and 34, 51, 70% more active than AgNPs with 4-day and 15-day treatment, respectively. Therefore, the onset of ROX and antioxidant arena favors beneficial cellular drifting of NPs.

Combination of levetiracetam with sodium selenite prevents pentylenetetrazole-induced kindling and behavioral comorbidities in rats.

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.

Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in Pakistan.

Background: Vancomycin is a narrow therapeutic agent, and it is necessary to optimize the dose to achieve safe therapeutic outcomes. The purpose of this study was to identify the significant covariates for vancomycin clearance and to optimize the dose among surgical patients in Pakistan. Methods: Plasma concentration data of 176 samples collected from 58 surgical patients treated with vancomycin were used in this study. A population pharmacokinetic model was developed on NONMEM® using plasma concentration-time data. The effect of all available covariates was evaluated on the pharmacokinetic parameters of vancomycin by stepwise covariate modeling. The final model was evaluated using bootstrap, goodness-of-fit plots, and visual predictive checks. Results: The pharmacokinetics of vancomycin followed a one-compartment model with first-order elimination. The vancomycin clearance (CL) and volume of distribution (Vd) were 2.45 L/h and 22.6 l, respectively. Vancomycin CL was influenced by creatinine clearance (CRCL) and body weight of the patients; however, no covariate was significant for its effect on the volume of distribution. Dose tailoring was performed by simulating dosage regimens at a steady state based on the CRCL of the patients. The tailored doses were 400, 600, 800, and 1,000 mg for patients with a CRCL of 20, 60, 100, and 140 ml/min, respectively. Conclusion: Vancomycin CL is influenced by CRCL and body weight of the patient. This model can be helpful for the dose tailoring of vancomycin based on renal status in Pakistani patients.

Removal of Broken Cannulated Drill Bit.

Breaking of surgical drill bits and subsequent dislodging in the bone are quite common in the field of orthopedics. Even though a few methods have been reported to remove dislodged drill bits, we present a novel method to remove a broken drill bit without additional instruments or a secondary incision. A broken cannulated drill bit within the locking screw hole inside the neck of a femur was retrieved using a depth gauge with a curved tip that hooked onto the edge of the drill bit. By employing a clockwise and counter-clockwise twisting, the broken drill bit was retrieved through the proximal reaming tract. The 4mm tract, which was established by proximal reaming, immensely facilitated safe and time-efficient removal of the drill tip without further trauma or prolonging the surgery time. With our technique, the removal was simple and safe without further soft tissue trauma and blood loss. We advocate this approach for implementation in similar cases.