Safety of purified Vero cell rabies vaccine manufactured in Pakistan: a comparative analysis of intradermal and intramuscular routes.

BACKGROUND: Rabies vaccines are conventionally given via the intramuscular (IM) route; however, switching the route of administration from IM to intradermal (ID) without affecting efficacy can be advantageous in terms of cost, dosing, and time. Hence, it is indispensable to evaluate its safety along different routes. This study was carried out to ascertain the frequency of adverse drug events (ADEs) and associated factors, as well as to compare safety based on the IM and ID routes. METHODS: A prospective observational study was carried out on 184 individuals with rabies exposure. The vaccination schedules for post-exposure prophylaxis (PEP) included 0.2 milliliter (mL) of purified Vero cell rabies vaccine (PVRV) administered ID at two different sites with 0.1 mL each on days 0, 3, and 7 in first group (3-dose regimen ID) and 0.5 mL administered IM on days 0, 3, 7, 14, and 28 in the second group (5-dose regimen IM). The safety of the vaccines was determined by reviewing ADEs during physical examinations and follow-up. ADEs were characterized by local and systemic effects. RESULTS: Of the total, 99 (53.80%) patients reported ADEs. Those who reported local and systemic ADEs were 80 (43.48%) and 59 (32.06%), respectively, while simultaneous occurrence was reported in 40 (40.40%) patients. The most frequent local ADE (76; 41.30%) reported was pain, followed by erythema (18; 9.78%). Additionally, fever had the highest proportion (25; 13.59%) for systemic effects, followed by headache (15; 8.15%). The patients reported with ADEs by the IM and ID routes were comparable (p >.05). Similarly, both local and systemic effects were also comparable (p >.05). CONCLUSION: Half of the study participants reported ADEs. Almost similar proportions of local and systemic effects were observed. Likewise, the ADEs recorded were comparable for both routes. PVRV carries very low safety concerns with either route for administration.

Synergistic application of calcium oxide nanoparticles and farmyard manure induces cadmium tolerance in mung bean (Vigna radiata L.) by influencing physiological and biochemical parameters.

Mung bean (Vigna radiata L.) grown under heavy metals such as cadmium stress shows poor growth patterns and yield attributes which can be extenuated by the application of calcium and organic manure to the contaminated soil. The present study was designed to decipher the calcium oxide nanoparticles and farmyard manure-induced Cd stress tolerance through improvement in physiological and biochemical attributes of mung bean plants. A pot experiment was conducted by defining appropriate positive and negative controls under differential soil treatments with farmyard manure (1% and 2%) and calcium oxide nanoparticles (0, 5, 10, and 20 mg/L). Root treatment of 20 mg/L calcium oxide nanoparticles (CaONPs) and 2% farmyard manure (FM) reduced the cadmium acquisition from the soil and improved growth in terms of plant height by 27.4% compared to positive control under Cd stress. The same treatment improved shoot vitamin C (ascorbic acid) contents by 35% and functioning of antioxidant enzymes catalase and phenyl ammonia lyase by 16% and 51%, respectively and the levels of malondialdehyde and hydrogen peroxide decreased by 57% and 42%, respectively with the application of 20 mg/L CaONPs and 2% of FM. The gas exchange parameters such as stomata conductance and leaf net transpiration rate were improved due to FM mediated better availability of water. The FM improved soil nutrient contents and friendly biota culminating in good yields. Overall, 2% FM and 20 mg/L CaONPs proved as the best treatment to reduce cadmium toxicity. The growth, yield, and crop performance in terms of physiological and biochemical attributes can be improved by the application of CaONPs and FM under the heavy metal stress.

Analysis of antidiabetic, antiulcer and analgesic potential of traditional ethnomedicinal plant Emex spinosa (L.) Campd. from Azad Jammu and Kashmir.

In this research antidiabetic, analgesic and antiulcer potential of traditional ethnomedicinal plant: Emex spinosa (L.) Campd. (Family Polygonaceae) was evaluated by extracting its phytoconstituents using methanol (MeOH) solvent through maceration protocol. The quantitative phytochemical analysis of the extract revealed flavonoids were highest in leaf extract (15.63±0.93 mg/mL) and with (11.5±0.57 mg/mL) in stem. Alkaloids and tanins were also present in the samples in various conc. while saponins were absent. To confirm pharmaceutical potential of plant against ulcer, diabetes and analgesic infirmities, a model experimental animal wistar albino rats (Rattus norvegicus) were used. In antiulcer study, using hot plate method the maximum results were observed with 250 mg/kg in the 2.5 hours of study. The leaf extract showed a 40.41±2.73 latency time and the fruit with a 36.77±2.41, and the stem with a 27.85±3.09, which was comparable to the standard drug Aspirin, i.e., 47.5±0.57. For analysis of antiulcer potential of the plants parts doses of 250 and 500 mg/kg was applied to check the reclamation of ethanol-induced acute ulcer and of Aspirin-induced chronic ulcer of stomach. In order to confirm efficacy of the drug potential of plant following parameters like microscopic evaluation, gastric volume, total acidity, mucosa weight, ulcer index, pH and histopathology of stomach were analyzed. In antidiabetic analysis, in an acute study after a single dose of 500 mg/kg extract after 2hrs the blood glucose levels were 367±51.09958NS, 416±59.79548NS, 437.5±61.96437NS mg/dL for leaf, stem and fruit, respectively. After4hrs 351.75±88.27644NS mg/dl, 448.25±25.64948NS mg/dl, 445.25±27.07205NS mg/dl and after 6hrs 354.5±92.70428NS, 442±24.60691NS, a440±33.16625NS mg/dl, respectively. The analgesic activity was explored by applying hot plate, tail flick and formalin paw licking method. In hot plate method the maximum results were observed with 250mg/kg in the 2.5 hours of study. The leaf extract showed a 40.41±2.73 latency time and the fruit with a 36.77±2.41 and the stem with a 27.85±3.09, which was comparable to the standard drug Aspirin, i.e., 47.5±0.57. The respective plant extracts at 250mg/kg showed a gradual rise in latency time when compared to the control. It was concluded that all three components of E. spinosa perform proved to be significant as potential source of herbal medicines to cure different prevalently occurring diseases. Furthermore, it was confirmed through results analysis that plant t can be used to discover novel drug using dedicated high throughput techniques and ethnopharmacological approaches.

Synthesis and In Vitro/Ex Vivo Characterizations of Ceftriaxone-Loaded Sodium Alginate/poly(vinyl alcohol) Clay Reinforced Nanocomposites: Possible Applications in Wound Healing.

(1) Background: Nanocomposite films are widely applied in the pharmaceutical industry (e.g., nanodrug delivery systems-NDDS). Indeed, these nanomaterials can be produced at a large industrial scale and display valuable properties (e.g., antibacterial, renewability, biodegradability, bioavailability, safety, tissue-specific targeting, and biocompatibility), which can enhance the activity of conventional marketed drugs. (2) Aim: To fabricate and investigate the in vitro properties of the antibiotic ceftriaxone sodium (CTX) once encapsulated into sodium alginate (SA)/poly(vinyl alcohol)PVA-clay reinforced nanocomposite films. (3) Methods: Different ratios of the polymers (i.e., SA, PVA) and CTX drug were used for the synthesis of nanocomposite films by solvent casting technique. Montmorillonite (MMT), modified organically, was added as a nanofiller to increase their thermal and mechanical strength. The prepared samples were physically characterized by thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electronic microscopy (SEM), and energy-dispersive X-ray analysis (EDX). The physicochemical behavior (i.e., swelling, erosion, dissolution/drug release behavior and rat skin permeation) was also assessed. Comparisons were made with the currently marketed free CTX dosage form. (4) Results: TGA of the nanoformulation showed increased thermostability. XRD revealed its semi-crystalline nature. SEM depicted a homogeneous drug-loaded SA/PVA nanocomposite with an average size ranging between 300 and 500 nm. EDX confirmed the elemental composition and uniform distribution of mixing components. The water entrapment efficiency study showed that the highest swelling and erosion ratio is encountered with the nanoformulations S100(3) and S100D15(3). Ex vivo permeation revealed a bi-step discharge mode with an early burst liberation chased by continued drug discharge of devised nanoparticles (NPs). The dissolution studies of the drug-loaded polymer nanocomposites elicited sustained pH-dependent drug release. The cumulative drug release was the highest (90.93%) with S100D15(3). (5) Conclusion: S100D15(3) was the finest formulation. To the best of our knowledge, we also pioneered the use of solvent casting for the preparation of such nanoformulations. Polymers and reinforcing agent, concentrations and pH were rate-deterring features for the preparation of the optimized formulation. Thus, CTX-loaded SA/PVA-MMT reinforced nanocomposite appeared as a promising nanodrug delivery system (NDDS) based on its in vitro physicochemical properties.

Antimicrobial activities of different solvent extracts from stem and seeds of Peganum Harmala L.

Wild medicinal herbs have been used as folk and traditional medicines all across the world since well before recorded history. This present study was designed to test the antimicrobial activities of five different solvent extracted samples (n-hexane, n-butanol, ethyl acetate, methanol, and water) of Peganum harmala using stems and seeds. Two different strains of Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), two Gram-positive bacteria (Bacillus subtilus and Staphylococcus aureus), and one fungal strain (Candida albicans) were used. The antimicrobial activities were measured using a disc diffusion assay. Two concentrations of the extracts (1 and 2mgDisc-1) were used. Ethyl acetate fraction was found more affective among the tested solvents and showed maximum activity (zone of inhibition) against S. aureus (65.53 and 81.10%), E. coli (46.22 and 61.29%) while n-butanol and water fractions gave maximum activity against S. aureus (78.86 and 70.00%) and K. pneumonia (57.00 and 61.39%) respectively. Water fraction showed maximum activity against C. albicans (60.00 and 81.88%). In the case of the stem, Ethyl acetate again showed more activity against B. subtilus (38.57 and 42.10%) and S. aureus (36.66 and 46.66%) while n-butanol showed maximum activity against K. pneumonia (24.55 and 32.44%) and E. coli (27.93 and 37.61%). Methanol was found more effective against C. albicans (25.71 and 43.80%). Seed extracted samples were found more effective compared to the stem. Ethyl acetate, butanol, and aqueous extracted samples showed good activity against the tested microbes, so these fractions are recommended for study their mechanism of actions and isolation of bioactive metabolites responsible for antimicrobial activities. The P. harmala should be evaluated for their bioactive compounds to be used in future studies. Our objective is to provide the framework for future study on the roles of P. harmala as traditional medicines.

Biogenic Synthesis of Silver Nanoparticles Using Phagnalon niveum and Its In Vivo Anti-Diabetic Effect against Alloxan-Induced Diabetic Wistar Rats.

Background: Type-2 diabetes mellitus (T2DM) is a non-communicable, life-threatening syndrome that is present all over the world. The use of eco-friendly, cost-effective and green synthesised nanoparticles (NPs) as a medicinal therapy in the treatment of T2DM is an attractive option. Aim: The present study aimed to evaluate the anti-diabetic potential of the phyto-synthesised silver nanoparticles (AgNPs) obtained from Phagnalon niveum plant methanolic extract. Methods: The green synthesised AgNPs made from Phagnalon niveum plant methanolic extract were analysed by Ultraviolet-Visible (UV-Vis) spectroscopy, and the functional groups involved in the reduction of the silver ions (Ag+) were characterised by Fourier Transform Infrared (FTIR) spectroscopy. The size and crystallinity were assessed via X-ray Diffraction (XRD). The morphology of AgNPs was confirmed using Scanning Electron Microscopy (SEM). The amount of silver (Ag) was estimated via energy dispersive X-ray (EDX) analysis. An intraperitoneal injection of 200 mg alloxan per kg albino Wistar rats' body weight, at eight weeks old and weighing 140-150 g, was used to induce diabetes mellitus (N = 25; n = 5/group). Group C: untreated normal control rats that only received distilled water, group DAC: diabetic control rats that received alloxan 200 mg/Kg body weight, DG: diabetic rats treated with glibenclamide at 0.5 mg/kg body weight, DE: diabetic rats that received methanolic P. niveum extract at 10 mg/Kg body weight, and DAgNPs: diabetic rates that received AgNPs synthesised from P. niveum at 10 mg/kg body weight. The blood glucose levels were monitored on days 0, 7, and 14, while lipid, liver, and kidney profiles were checked after dissection at the end of treatment (day 21). On the final day of the period study (day 21), an oral glucose tolerance test was carried out by administering orally 2 g/kg body weight of glucose to the respective groups, and the blood glucose level was checked. A fasting glucose level was measured using a glucometer. Urine samples were collected from each animal and analysed using lab-made assay kits for glucose, bilirubin, pH, leukocytes, and nitrite, among other factors. For statistical analyses, a one-way ANOVA and Dunnett's test were applied. Results: The green-mediated synthesis of AgNPs using P. niveum methanolic extract produced spherical and mono-dispersed NPs with a size ranging from 12 to 28 nm (average: 21 nm). Importantly, a significant reduction of blood glucose levels and an increase in body weight, as well as a remarkable improvement in lipid, liver, and kidney profiles, were noticed. Conclusions: The biosynthesised AgNPs significantly improved the abnormalities in body weight, urine, and serum levels, indicating that it is a promising anti-diabetic agent.

Possible Role of Sildenafil Citrate in the Recurrence of Neovascularization in Laser-regressed Aggressive Posterior ROP.

BACKGROUND: Systemic diseases and their treatment influence aggressive posterior retinopathy of prematurity. CASE CHARACTERISTICS: A premature infant with aggressive posterior retinopathy of prematurity underwent laser treatment with a favourable outcome. She was started on oral sidenafil citrate for pulmonary hypertension. Ten days later she developed neovascularization within the lasered retina. INTERVENTION/OUTCOME: Considering the possible role of sildenafil in this unusual development, the drug was withdrawn resulting in regression of the neovascularization. MESSAGE: The clinician should be aware of this retinal adverse effect of sildanefil in neonates with aggressive posterior retinopathy of prematurity.