Assessment of the advantages and limitations of an innovative silk fibroin scaffold for the reconstruction of the anterior cruciate ligament with preclinical in vitro and in vivo evaluations

Article

Author: Ghezzi, Chiara E ; Giavaresi, Gianluca ; Fini, Milena ; Ghezzi, Chiara E. ; Sartori, Maria ; Freddi, Giuliano ; Del Piccolo, Nicolandrea ; Dallari, Dante ; Erani, Paolo ; Martini, Lucia ; Brogini, Silvia ; Farè, Silvia ; Baleani, Massimiliano ; Tanzi, Maria Cristina ; Alessandrino, Antonio ; Parrilli, Annapaola ; Boschi, Alessandra

The gold standard treatment in anterior cruciate ligament (ACL) reconstruction involves autologous tissue transplantation, but this can have complications. Artificial grafts are an alternative, but the best option is debated. This study aimed to assess the biocompatibility and integration of a silk fibroin textile prosthesis (SF-TP) with peri-implant bone tissue and the native ACL. Twenty-six sheep underwent ACL reconstruction with SF-TP or autologous femoral fascia lata (FFL). Sheep were divided into two groups (3 and 6 months) and retrieved joints processed for histological, morphometrical and mechanical analysis. In vitro, SF-TP showed no cytotoxicity and good cell interaction up to 14 days. Histology revealed fibro-vascular tissue around SF-TP, with a progressive attempt of ligamentous-like tissue formation at 6 months. However, SF-TP group had higher joint damage scores. Micro-CT showed tunnel enlargement in SF-TP group, while FFL group had a decrease. SF-TP reconstructions had lower stiffness and strength (44 % and 64 % decrease) than those of autologous FFL reconstruction and often failed by pull-out from the bone tunnel due to tunnel enlargement. These results indicate poor osteointegration and graft motion with SF-TP, leading to joint damage/bone resorption and reduced mechanical competence. These results do not support the use of SF-TP for ACL reconstruction.

01 May 2024·Journal of Electrocardiology

The effect of anabolic androgenic steroids on heart rate recovery index and electrocardiographic parameters in male bodybuilders

Article

Author: Baytugan, Nart Zafer ; Kandemir, Hasan Çağlayan

BACKGROUNDThe control of the cardiovascular system depends on the autonomic nerve system. Chronic anabolic andorogenic steroids (AAS) use causes sympathovagal imbalance and increases sympathetic nerve activity.OBJECTIVEThe reduction in heart rate from the peak exercise rate following the end of the exercise stress test is known as the heart rate recovery index (HRRI). Several methods have been utilized to assess myocardial repolarization, such as QT interval (QT), corrected QT interval (QTc), and T-wave peak-to-end interval (Tp-e interval). Based on a growing number of data a higher Tp-e/QT ratio is linked to malignant ventricular arrhythmias, and an increased Tp-e interval may correlate with the transmural dispersion of repolarization. Our hypothesis is that the use of chronic AAS was decrease HRRI during maximal exercise and increased risk of cardiac arrhythmias and sudden cardiac death.METHODSThis study included 44 male bodybuilders, with an average age of 29.7 ± 8.14 years, divided into AAS abuse [AAS users (n = 21) and AAS nonuser (n = 23)].RESULTSThe first (p = 0.001) and second minute (p = 0.001) HRRI of the subjects with AAS users were significantly lower than those of the control group. Additionally, HRRI after the third (p = 0.004) and fifth minutes (p = 0.007) of the recovery period were significantly lower in AAS group compared with the control group. Who used AAS had significantly higher QT, QTc, Tp-e, Tp-e/QT, and Tp-e/QTc values than non-users (all p = 0.001).CONCLUSIONSChronic AAS use has been shown to cause sympathetic dominance, which may be a pro arrhythmic state.

01 May 2024·AIDS Research and Human Retroviruses

Intracellular Islatravir-Triphosphate in Dried Blood Spots and Peripheral Blood Mononuclear Cells from Pig-Tailed Macaques

Article

Author: Rohan, Lisa ; Abdelmawla, Farah ; Bushman, Lane ; Choi, Ye Ji ; Nerguizian, David ; Brooks, Kristina ; Patton, Dorothy ; Patel, Sravan Kumar ; Mainella, Vincent ; Anderson, Peter ; Cosgrove Sweeney, Yvonne ; Morrow, Mary

The purpose of this study was to evaluate the relationship between intracellular islatravir-triphosphate (ISL-TP) in paired peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS). Three pig-tailed macaques (PMs) were dosed with a single intravaginal extended-release ISL-etonogestrel film for a period of 31 days. After extraction and quantification, repeated measures correlation (r_rm) was assessed between log-transformed DBS and PBMC ISL-TP concentrations. Twenty-six paired PBMC/DBS samples were included. Peak ISL-TP concentrations in DBS ranged from 262 to 913 fmol/punches, PBMC C_max ranged from 427 to 857 fmol/10⁶ cells. Repeated measures correlation yielded an r_rm value of 0.96 (95% confidence interval 0.92-0.98; p < .0001). Importantly, ISL-TP was quantifiable in DBS and its pharmacokinetics were similar to PBMC in PMs. Human studies should evaluate DBS applications in clinical pharmacokinetic studies to help define ISL's place in the antiretroviral drug armamentarium.

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Indication	Highest Phase	Country/Location	Organization	Date
Metabolic Diseases	Phase 2	-	Aofen Technology Co., Ltd.	-
Mitochondrial Myopathies	Discovery	GB	Aofen Technology Co., Ltd.	27 Feb 2020

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