Dibucaine in Ionic-Gradient Liposomes: Biophysical,Toxicological, and Activity Characterization

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC.     

Mitigation of Oxidation in Therapeutic Antibody Formulations: a Biochemical Efficacy and Safety Evaluation of <Emphasis Type="Italic">N</Emphasis>-Acetyl-Tryptophan and L-Methionine

Purpose

Biotherapeutics can be susceptible to oxidation during manufacturing and storage. Free L-methionine is known to protect methionine residues in proteins from oxidation. Similarly, free tryptophan and other indole derivatives have been shown to protect tryptophan residues from oxidation. N-acetyl-DL-tryptophan was previously identified as a potentially superior antioxidant to tryptophan as it has a lower oxidation potential and produces less peroxide upon light exposure. This study sought to confirm the antioxidant efficacy and safety of N-acetyl-DL-tryptophan and L-methionine as formulation components for biotherapeutic drugs.

Methods

Antibodies were subjected to AAPH and light exposure in the presence of N-acetyl-DL-tryptophan and L-methionine. Oxidation in relevant CDR and Fc residues was quantified by peptide map. In silico, in vitro, and in vivo studies were performed to evaluate the safety of N-acetyl-DL-tryptophan and L-methionine.

Results

Peptide mapping demonstrated that N-acetyl-DL-tryptophan was effective at protecting tryptophans from AAPH stress, and that the combination of N-acetyl-DL-tryptophan and L-methionine protected both tryptophan and methionine from AAPH stress. The safety assessment suggested an acceptable safety profile for both excipients.

Conclusions

N-acetyl-tryptophan and L-methionine effectively reduce the oxidation of susceptible tryptophan and methionine residues in antibodies and are safe for use in parenteral biotherapeutic formulations.

     

PROBLEMATIC INTERNET USE AMONG ADULT JAPANESE PSYCHIATRIC PATIENTS

Background

A large number of studies have reported the high prevalence of problematic internet use (PIU) among adolescents and students (13-50%)¹, and PIU has been associated with many psychiatric symptoms². In contrast, only a few studies have investigated its prevalence among the adult population. To the best of our knowledge, there have been no studies investigating the prevalence and comorbidity of PIU in a psychiatric population although psychiatric symptoms might either induce PIU in patients with psychiatric illnesses, or PIU might induce or aggravate psychiatric symptoms. The aims of this study are to investigate the prevalence of PIU and psychiatric co-morbidity among adult psychiatric patients.

Visual and auditory emotion recognition problems as familial cross-disorder phenomenon in ASD and ADHD

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are frequently comorbid disorders. Emotion recognition problems are considered an important familial deficit in ASD, but this is unknown in ADHD. Very few studies have directly compared emotion recognition performance of youth with ASD and/or ADHD and of their unaffected siblings across age to quantify the contribution of emotion recognition problems to the ADHD phenotype. We therefore devised a study of 64 ASD+ADHD participants, 89 ASD-only participants, 111 ADHD-only participants, 122 unaffected ASD(+ADHD) siblings, 69 unaffected ADHD-only siblings and 220 controls aged 7–18 years, who had completed two tasks assessing auditory and visual emotion recognition. Factor analysis was used to detect underlying dimensions of emotion recognition capacity. Linear mixed models were used to compare performance across groups and to assess age effects. The factor-analysis revealed four factors separating speed and accuracy regarding visual and auditory emotion recognition. ASD+ADHD, ASD-only, and ADHD-only participants all performed worse than controls. ASD+ADHD, ASD-only, and ADHD-only participants did not differ in the severity of their emotion recognition problems. Both unaffected sibling groups performed intermediate between patients and controls. For ASD+ADHD and ADHD-only participants, group differences were more marked in adolescence than childhood, whereas in ASD participants this was not observed. We conclude that emotion recognition problems are a familial deficit in ADHD to a similar extent as in ASD. Emotion recognition problems specifically - and social cognition problems more generally - should be assessed in clinical practice for ADHD.     

Bauhinia forficata in the treatment of diabetes mellitus: a patent review

Introduction: Diabetes Mellitus has been considered an epidemic by the World Health Organization, with a high risk of morbidity and mortality. The treatment of this pathology consists in glycemic control, which can be done by oral hypoglycemic agents, insulin therapy, dietary guidance, regular physical activity, and psychosocial support. In addition, other adjuvant treatments are employed, such as phytotherapic, and one of the most used plants is Bauhinia forficata.

Areas covered: In the current review, patents using Bauhinia forficata for the Diabetes Mellitus treatment have been analyzed. There were 03 patents in WIPO, 01 in Espacenet, 01 in USPTO, and 02 in INPI.

Expert opinion: Patents on the adjuvant treatment of Diabetes Mellitus by Bauhinia forficata are discussed. Although there are some phytotherapy products containing this medicinal plant which has hypoglycemic effect here is still a need for the development of more products based on natural resources, for the treatment of this pathology, without side effects and with other benefits, to assist in the glycemia control in diabetic patients, and to improve their quality of life.     

New,Immunomodulatory, Oral Nutrition Formula for Use Prior to Surgery in Patients With Head and Neck Cancer: An Exploratory Study

Background: The perioperative use of immunomodulatory nutrition formulas in patients with head and neck cancer reduces the number of postoperative infections and the length of hospital stay. Objective: An exploratory, randomized, controlled, blind, clinical trial was designed to examine the effect of the preoperative consumption of a new, immunomodulatory, oral nutrition formula in patients with head and neck cancer. Methods: Thirty‐eight patients were randomized to receive either 400 mL/d of either the new immunomodulatory formula (IF) or that commonly used in clinical practice (CF) over 10 days prior to surgery. Thirty‐three patients completed the study. Compliance, tolerance, the length of hospital stay, the incidence of infections and noninfectious complications before discharge, and the same up to 15 and 30 days after discharge were recorded. Results: The percentage of patients who developed infections before discharge was significantly lower in the IF than in the CF group (P = .013), as was the number of infections/100 patients/d (P = .035). The length of hospital stay was significantly shorter in the IF group (P = .001). Both formulas were safe and well tolerated. No other differences were detected. These results suggest preoperative consumption of the new formula to be beneficial for patients with neck and head cancer. Further trials are needed to confirm these results and to test the efficacy of the formula in patients with other conditions. Conclusion: The new formula can be safely prescribed as part of the preoperative treatment of patients with head and neck cancer and might reduce the problem of postoperative infection.