A Case Report of Acute Severe Necrotizing Pancreatitis following the Johnson & Johnson Vaccine against the Novel SARS-CoV-2.

Acute pancreatitis is an inflammatory condition, which is a leading gastrointestinal cause of hospitalization in the United States. Several conditions are associated with acute pancreatitis. More recently, there have been a few cases reported of acute pancreatitis following the Pfizer-BioNTech COVID-19 mRNA vaccine. To our knowledge, no cases of acute pancreatitis have been yet reported following the Johnson & Johnson's Janssen COVID-19 vaccine (J& J vaccine). Herein we report a 34-year-old male with no significant past medical history admitted with acute necrotizing pancreatitis, the day following the receipt of the J&J vaccine. Based on the Naranjo and the modified Naranjo scale, the patient met the requirements for probable drug induced pancreatitis. This case report has the objective to raise awareness of a potentially severe side effect of the J&J vaccine. We hope to use this case to support screening all patients for previous history of acute pancreatitis before administration of the J& J vaccine.

Pyrus communis L. (Pear) and Malus domestica Borkh. (apple) leaves lipoidal extracts as sources for beta-sitosterol rich formulae and their wound healing evaluation.

Pyrus communis L. (cv. Le-Conte) (pears) and Malus domestica Borkh. (cv. Anna) (apples) are economic fruit crops cultivated in Egypt. Their leaves were assessed for their beta-sitosterol content and found to have 9.4 mg/g dried leaves wt and 5 mg/g dried leaves, respectively. So we used the lipoidal leaves extracts in the formulation of eight beta-sitosterol-rich emulgels from which the most stable formulae were tested for their antimicrobial activity. Finally, the formulae which exerted antimicrobial activity were biologically evaluated for wound healing against well-known wound healing ointment Mebo® which is composed mainly of 0.25% beta-sitosterol in a base of sesame oil and beeswax. Wound contraction was statistically different in both formulae F3 and F8 from both control and Mebo® groups which indicated better wound healing activity of these formulae ensured by further histopathological study of the healed wounds.

Itraconazole-Loaded Ufasomes: Evaluation, Characterization, and Anti-Fungal Activity against Candida albicans.

Numerous obstacles challenge the treatment of fungal infections, including the uprising resistance and the low penetration of available drugs. One of the main active agents against fungal infections is itraconazole (ITZ), with activity against a broad spectrum of fungi while having few side effects. The aim of this study was to design ufasomes, oleic acid-based colloidal carriers, that could encapsulate ITZ to improve its penetration power. Employing a 2231 factorial design, the effect of three independent factors (oleic acid amount, cholesterol concentration, and ITZ amount) was investigated and evaluated for the percentage encapsulation efficiency (%EE), particle size (PS), and zeta potential (ZP). Optimization was performed using Design® expert software and the optimized ITZ-loaded ufasomes obtained had %EE of 99.4 ± 0.7%, PS of 190 ± 1 nm, and ZP of -81.6 ± 0.4 mV, with spherical unilamellar morphology and no aggregation. An in vitro microbiological study was conducted to identify the minimum inhibitory concentration of the selected formula against Candida albicans, which was found to be 0.0625 µg/mL. Moreover, the optimized formula reduced the expression of toll-like receptors-4 and pro-inflammatory cytokine IL-1ß secretion in the C. albicans-infected fibroblasts, indicating that the proposed ITZ-loaded ufasomes are a promising drug delivery system for ITZ.

Sleep extension reduces pain sensitivity.

INTRODUCTION: Insufficient sleep increases pain sensitivity in healthy individuals. Additionally, extending sleep (eg, increasing nocturnal sleep time or adding a mid-day nap) has been shown to restore pain sensitivity to baseline levels in sleep deprived/restricted individuals. Whether sleep extension can reduce pain sensitivity beyond baseline levels in non-sleep restricted/deprived individuals remains unknown. METHODS: In a sample of 27 healthy, pain-free, normally-sleeping individuals (17 males, mean age ∼24 yrs), we examined the impact of five nights of sleep extension on pain sensitivity. Pain threshold (elapsed time until the participant reported pain) and pain tolerance (total time the participant kept the hand submerged in the cold water) were measured using the Cold Pressor Task. Furthermore, we assessed the extent to which self-reported sleep amount in relation to the minimal subjective sleep requirement for adequate performance (sleep credit) was associated with pain sensitivity changes. RESULTS: On average individuals slept almost 2 extra hours per night. Our results indicate that sleep extension increases pain tolerance beyond baseline levels. However, sleep extension did not impact pain threshold. We also found that individuals with a smaller sleep credit (ie, those who habitually obtain less sleep than they feel they need) experienced greater increases in pain tolerance after extending sleep. CONCLUSIONS: The present findings suggest that sleep extension may increase pain tolerance but not pain threshold in healthy individuals who normally sleep the recommended amount. Our findings also support the idea that sleep credit may be a strong indicator of sleep debt in the context of pain sensitivity.

Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures.

Dorzolamide hydrochloride is frequently administered for the control of the intra-ocular pressure associated with glaucoma. The aim of this study is to develop and optimize self-assembled nanostructures of dorzolamide hydrochloride and L-α-Phosphatidylcholine to improve the pharmacokinetic parameters and extend the drug pharmacological action. Self-assembled nanostructures were prepared using a modified thin-film hydration technique. The formulae compositions were designed based on response surface statistical design. The prepared self-assembled nanostructures were characterized by testing their drug content, particle size, polydispersity index, zeta potential, partition coefficient, release half-life and extent. The optimized formulae having the highest drug content, zeta potential, partition coefficient, release half-life and extent with the lowest particle size and polydispersity index were subjected to further investigations including investigation of their physicochemical, morphological characteristics, in vivo pharmacokinetic and pharmacodynamic profiles. The optimized formulae were prepared at pH 8.7 (F5 and F6) and composed of L-α-Phosphatidylcholine and drug mixed in a ratio of 1:1 and 2:1 w/w, respectively. They showed significantly higher Cmax, [Formula: see text] and [Formula: see text] at the aqueous humor with extended control over the intra-ocular pressure, when compared to the marketed product; Trusopt®. The study introduced novel and promising self-assembled formulae able to permeate higher drug amount through the cornea and achieve sustained pharmacological effect at the site of action.

Response surface optimization, Ex vivo and In vivo investigation of nasal spanlastics for bioavailability enhancement and brain targeting of risperidone.

Transnasal brain drug targeting could ensure better drug delivery to the brain through the olfactory pathway. Risperidone bioavailability is 66% in extensive metabolizers and 82% in slow metabolizers. The aim of this study is to investigate the ability of the nanovesicular spanlastics to effectively deliver risperidone through the nasal route to the brain and increase its bioavailability. Spanlastics formulae, composed of span and polyvinyl alcohol, were designed based on central composite statistical design. The planned formulae were prepared using ethanol injection method. The prepared formulae were characterized by testing their particle size, polydispersity index, zeta potential and encapsulation efficiency. The optimized formula having the lowest particle size, polydispersity index, the highest zeta potential and encapsulation efficiency was subjected to further investigations including characterization of its rheological properties, elasticity, transmission electron microscopy, in vitro diffusion, ex vivo permeation, histopathology and in vivo biodistribution. The optimized formula was composed of 5mg/mL span and 30mg/mL polyvinyl alcohol. It showed significantly higher transnasal permeation and better distribution to the brain, when compared to the used control regarding the brain targeting efficiency and the drug transport percentage (2.16 and 1.43 folds increase, respectively). The study introduced a successful and promising formula to directly and effectively carry the drug from nose to brain.

Investigating the cubosomal ability for transnasal brain targeting: In vitro optimization, ex vivo permeation and in vivo biodistribution.

The aim of this study was to enhance the risperidone delivery to the brain through the transnasal route via optimization of cubosomal gel. Cubosomes were prepared using glycerol mono-oleate (GMO), Pluronic F127 (PF127) and Tween 80 (T80). The prepared formulae were characterized by testing their particle size, polydispersity index, zeta potential, entrapment efficiency, in vitro drug release and transmission electron microscopy. Central composite design was planned for the formulae optimization and the selected formula (containing PF127 with concentration 15 mg/g GMO and T80 with concentration of 20mg/L) was re-prepared in presence of gelling polymer (gellan gum or polyox). The optimal cubosomal gel (containing 0.4% w/v polyox) had been subjected to ex-vivo permeation, histopathological evaluation and in vivo biodistribution studies. It showed significantly higher transnasal permeation and better distribution to the brain, when compared to the used control (drug solution and/or suspension). Finally, the cubosomal gel could be considered as a promising carrier for brain targeting of CNS acting drugs through the transnasal route.