Design,characterization and evaluation of β-hairpin peptide hydrogels as a support for osteoblast cell growth and bovine lactoferrin delivery

The use of peptide hydrogels is of growing interest in bone regeneration. Self-assembling peptides form hydrogels and can be used as injectable drug delivery matrices. Injected into the defect site, they can gel in situ, and release factors that aid bone growth. We report on the design, synthesis and characterization of three β-hairpin peptide hydrogels, and on their osteoblast cytocompatibility as well as delivery of the lactoferrin glycoprotein, a bone anabolic factor. Osteoblasts cultured in hydrogels of the peptide with sequence NH₂-Leu-His-Leu-His-Leu-Lys-Leu-Lys-Val-dPro-Pro-Thr-Lys-Leu-Lys-Leu-His-Leu-His-Leu-Arg-Gly-Asp-Ser-CONH₂ (H4LMAX-RGDS) increased the osteoblast cell number and the cells appeared healthy after seven days. Furthermore, we showed that H4LMAX-RGDS was capable of releasing up to 60% of lactoferrin (pre-encapsulated in the gel) over five days while retaining the rest of the glycoprotein. Thus, H4LMAX-RGDS hydrogels are cytocompatible with primary osteoblasts and capable of delivering bio-active lactoferrin that increases osteoblast cell number.

Self-assembling peptide H4LMAX-RGDS hydrogels, designed to enhance bone regeneration, are cytocompatible and capable of delivering the bone anabolic factor lactoferrin to increase osteoblast cell number.     

Effect of substituents in the A and B rings of chalcones on antiparasite activity

Chalcones are a group of natural products with many recognized biological activities, including antiparasitic activity. Although a lot of chalcones have been synthetized and assayed against parasites, the number of structural features known to be involved in this biological property is small. Thus, in the present study, 21 chalcones were synthesized to determine the effect of substituents in the A and B rings on the activity against Leishmania braziliensis, Trypanosoma cruzi, and Plasmodium falciparum. The compounds were active against L. braziliensis in a structure-dependent manner. Only one compound was very active against T. cruzi, but none of them had a significant antiplasmodial activity. The electron-donating substituents in ring B and the hydrogen bonds at C-2′ with carbonyl affect the antiparasitic activity.     

Autologous fat as a rectal–prostate spacer for prostate brachytherapy: Results at 6 months

PurposeImplanted rectal spacers (IRS) have been developed to increase the distance between the prostate and the rectum, thus optimizing dose escalation. Cost is a disadvantage and there are still uncertainties as to their durability. We have developed an autologous fat transfer (AFT) technique to use as an IRS. We aim to present the feasibility and durability at 6 months of AFT placed immediately after the implant of the seeds in low-dose-rate brachytherapy (BT).Methods and MaterialsThirty-five patients underwent AFT (12 were treated with primary BT, 7 with a combined primary treatment of external beam radiotherapy + BT, 16 with salvage BT). The isodose used for primary BT was 14400 cGy, 11,000 cGy after 4600 cGy of external beam radiotherapy in the combined group, and 14400 cGy for the salvage group. Patients underwent a CT scan at 1, 3, and 6 months to measure the distance between the rectum and the prostate.ResultsAn average of 32.7 cc (20–40) of fat was transferred successfully in 100% of cases. The mean distance to the rectum at the level of the base, middle, and apex at 1 and 6 months were 11.2, 9.7, and 7.6 mm; 8.3, 8.1, and 5.9 mm, respectively. No rectal toxicity or major complications were reported.ConclusionsThe use of fat as an IRS seems to be a valid alternative to reduce rectal toxicity after BT, achieving equivalent distances to synthetic IRS. It is feasible, safe, and the loss of distance at 6 months is small. Cost is lower than other alternatives.     

Radiofrequency Ablation of Thyroid Nodules: A Long-Term Prospective Study of 24 Patients

PurposeTo evaluate the volume reduction rate (VRR) of thyroid nodules over a long period of time after radiofrequency (RF) ablation treatment in both solid and mixed nodules; to determine ablation parameters; and to evaluate complications and success rates and safety of RF ablation.Material and MethodsIn this prospective study, 24 patients (83% females and 17% males; age 50.17 ± 13.6 years) underwent ultrasound-guided percutaneous RF ablation of benign thyroid nodules with radiologic follow-up at 1, 3, 6, 12, 24, and 36 months after treatment. All patients presented with compressive or cosmetic complaints and with Thyroid Imaging Reporting and Data System 1 or 2 nodules under ultrasound and were confirmed to be Bethesda Category II after 2 fine-needle aspirations.ResultsA total of 24 nodules (54.2% solid, 37.5% solid predominance, and 8.3% cystic predominance) were included in this study. Significant results in VRR (%) were found at 24 months and 36 months of 69.92 ± 19.23 and 76.84 ± 15.92, respectively. Furthermore, a logarithmic relationship was found when VRR was plotted over time, in both solid and mixed nodules. No correlations were found with any of the ablation parameters. The success rate reached 72.22% at 12 months, and the total complication rate was 16.67% (12.5% minor complications and 4.2% major complications—1 laryngeal nerve palsy), reaching an 83.3% safety.ConclusionsRF ablation can be an alternative treatment modality in the management of benign symptomatic thyroid nodules. The results show that it is a safe and effective treatment if trans-isthmic approach and moving-shot techniques are correctly followed.     

An update on the use of benzoate,phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease

Introduction: Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal.

Areas covered: We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease.

Expert opinion: For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy. The efficacy and mechanisms underlying the antitumor effects of these ammonia-scavenging drugs in liver cancer are more controversial and are discussed in the review. Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer. Considering the relevance of glutamine metabolism to the progression and resolution of liver disease, we propose that ammonia-scavenging drugs might also be used to non-invasively probe liver glutamine metabolism in vivo. Finally, novel derivatives of classical ammonia-scavenging drugs with fewer and less severe adverse effects are currently being developed and used in clinical trials for the treatment of acute liver failure and cirrhosis.     

Meta-Analysis: Efficacy and Tolerability of Vesicular Monoamine Transporter Type 2 Inhibitors in the Treatment of Tic Disorders

Vesicular monoamine transporter type 2 (VMAT2) inhibitors may be an effective therapy for chronic tic disorders (CTD), including Tourette syndrome (TS), but there has not been a meta-analysis compiling available evidence from randomized controlled trials (RCTs). We performed a systematic review and meta-analysis to evaluate the efficacy, acceptability, and tolerability of VMAT2 inhibitors for CTD/TS. PubMed, CENTRAL, and Embase were searched for double-blinded RCTs of VMAT2 inhibitors versus placebo for the treatment of CTD/TS. Change in tic severity measured by the Yale Global Tic Severity Scale (efficacy) and rates of discontinuation attributed to adverse effects (tolerability) or all causes (acceptability) were extracted closest to 12 weeks. Mean difference (MD) and odds ratio (OR) were the effect size indexes for efficacy and acceptability/tolerability, respectively. Data were pooled through random-effects meta-analysis weighted by inverse variance. Five RCTs involving eight comparisons were included. Meta-analysis found a nonsignificant effect on efficacy (k = 8; N = 583; MD = −0.71; 95% confidence interval [CI], −1.93 to 0.50; P = 0.24), and there was certainty that the true effect is nonclinically meaningful (high quality of evidence). Meta-analysis found decreased tolerability (k = 7; N = 626; OR = 2.67; 95% CI, 1.21–5.92; P = 0.01) and decreased acceptability (k = 8; N = 626; OR = 1.90; 95% CI, 1.14–3.18; P = 0.01), although those comparisons were limited because of the relatively small number of events across trials. Meta-analyses did not support the efficacy of VMAT2 inhibitors in the short-term treatment of tic disorders and suggested no clinically meaningful effect of these agents on tic symptoms. © 2022 International Parkinson and Movement Disorder Society