Effect of BMP-12, TGF-β1 and autologous conditioned serum on growth factor expression in Achilles tendon healing

Purpose

Achilles tendon ruptures are devastating and recover slowly and incompletely. There is a great demand for biomolecular therapies to improve recovery, yet little is understood about growth factors in a healing tendon. Here, the role of growth factors during tendon healing in a rat model and their reaction to single and multiple growth factor treatment are explored.

Methods

Rat tendons were transected surgically and resutured. The expression of bFGF, BMP-12, VEGF and TGF-β1 was assessed by immunohistochemical analysis one to 8?weeks after surgery. Paracrine effects of TGF-β1 or BMP-12 added by adenoviral transfer, as well as the effect of autologous conditioned serum (ACS) on growth factor expression, were evaluated.

Results

bFGF, BMP-12 and VEGF expression was highest 1?week after transection. bFGF and BMP-12 declined during the remaining period whereas VEGF expression persisted. TGF-β1 expression dramatically increased after 8?weeks. ACS treatment increased bFGF (P?=?0.007) and BMP-12 (P?=?0.004) expression significantly after 8?weeks. Also overall expression of bFGF, BMP-12 and TGF-β1 regardless of time point was significantly greater than controls with ACS treatment (P?Conclusion bFGF, BMP-12, VEGF and TGF-β1 are differentially expressed during tendon healing. Additional BMP-12 or TGF-β1 has no significant influence, whereas ACS generally increases expression of all factors except VEGF. Staged application of multiple growth factors may be the most promising biomolecular treatment.     

Laparoscopic TOT–like Burch Colposuspension: Back to the Future?

ObjectiveTo demonstrate a modification of the classic Burch procedure, called “laparoscopic transobturator tape (TOT)–like Burch colposuspension.” The technique does not involve any type of prosthesis placement, and it is an alternative for patients with stress urinary incontinence in a future without meshes. Describing and standardizing the procedure in different steps makes the surgery reproducible for gynecologists and safe for the patients.DesignStep-by-step educational video, underlining and focusing on the main anatomical landmarks.SettingA university tertiary care hospital.InterventionsThe patient is set under general anesthesia and in lithotomy position. The distinct steps of the procedure are performed as followed: Step 1: Installation. Two 10-mm trocars are positioned in the midline and 2 5-mm trocars in the suprapubic region. The recommended intra-abdominal pressure is 6 to 8 mm Hg, and excessive Trendelenburg is not needed. Step 2: Entry in the Retzius space. The median umbilical ligament and the vesicoumbilical fascia are transected. Step 3: Exposure of the Retzius space and the anatomical structures. The dissection is continued consecutively toward the pubic bone and the Cooper's ligament, laterally toward the external iliac vessels and the corona mortis and medially toward the bladder neck. Step 4: Vaginal dissection. The pubocervical is dissected at the level of the pubourethral ligaments. Step 5: Suspension of the vagina to the Cooper's ligament. In contrast to the standard technique, with the TOT–like Burch, the sutures on the pubocervical fascia are placed at the level of the attachment of the arcus tendinous fascia pelvis and the pubourethral ligament. This way of suspension ensures a lateral traction on the bladder neck, resembling the effect of the TOT, which leads to lower incidence of dysuric symptoms. Step 6: Peritoneal closure.ConclusionThe classic colposuspension was created in 1961 for the treatment of stress urinary incontinence prolapse [1]. In the following years, vaginal meshes gained popularity as a treatment option for prolapse and for incontinence owing to their ease of use and satisfying results, which led to a decreased use of the Burch procedure [2,3]. In 2019, the Food and Drug Administration forbid the production of the transvaginal meshes for prolapse [4], an interdiction that could influence the use of synthetic meshes for incontinence in the future [5]. Owing to these recent events, searching for an effective way of management for patients with stress urinary incontinence without any synthetic prostheses, gynecologists have turned back to the 60-year-old Burch colposuspension. One of the drawbacks of the original technique is the high incidence of voiding difficulties—up to 22% [6]. Owing to the knowledge of the exact course of traction with the TOT, in our modified technique, the lateral direction of the suspension provides a tension-free support on the urethra and the bladder neck. The laparoscopic TOT–like Burch colposuspension is a safe and effective treatment for patients with stress urinary incontinence with low rates of dysuric symptoms and represents a valuable alternative for gynecologists in a future without meshes.     

Anticonvulsant evaluation and docking analysis of VV-Hemorphin-5 analogues

VV-Hemorphin-5 is an endogenous opioid peptide of the Hemorphin family with affinity at opioid receptors. A series of C-amide analogues have been synthesized, based on the structure of VV-Hemorphin-5, modified at position 1 and 7 by the un/natural amino acids ( Aa8 -Val-Val-Tyr-Pro-Trp-Thr-Gln-NH₂ and Val-Val-Tyr-Pro-Trp-Thr- Aa1 -NH₂) using SPPS, Fmoc-chemistry. The peptide derivatives were evaluated for their anticonvulsant activity in three acute seizure tests in male ICR mice, the maximal electroshock (MES), the 6 Hz psychomotor seizure test, and the timed intravenous pentylenetetrazole (ivPTZ) infusion test. Their neurotoxicity was assessed in the rotarod test. Among the tested peptide analogues, V4 showed anticonvulsant activity in the three seizure tests that was comparable to the VV-Hemorphin-5 (V1) used as a positive control. While V5, V6, and V7 peptide derivatives exhibited anticonvulsant activity in the MES and 6 Hz test, they were inactive (V7) or showed pro-convulsant effect (V5 and V6) in the i.v. PTZ test. At a dose of 10 μg/mouse the peptide V2 was effective against clonic seizures induced by PTZ. Motor coordination was not affected by newly developed analogues of VV-Hemorphin-5. Docking study results suggest that kappa opioid receptor binding could be the mechanism of action of peptide derivatives with anticonvulsant activity. The results suggest that incorporation of nonproteinogenic and/or natural amino acids at position 1 and 7 of the VV-Hemorphin-5 scaffold deserve further evaluation in models of epilepsy and derivatization.     

Thymoma type B2 progression,due to fear of contamination,in association with hydrocephalus: A case report of avoidant behavior during COVID-19 pandemic

The novel coronavirus pandemic outbreak caused extreme public fear, health concerns, and psychological distress, especially in oncology patients. The presented rare case is of a 40-year-old female with thymoma type B, with rapid progression, due to fear from the COVID-19 pandemic. Biopsy and histological verification of the tumor show a B-type thymoma with a high proliferative index. The fear of infection is causing avoidant behavior and leads to suboptimal therapy in some oncology patients that will have severe consequences. We can conclude that adequate, personalized, and most importantly, active psychological care is necessary and should be implemented for cancer patients. To be prepared for a future lockdown, it may be helpful to urge patients to seek alternative forms of social contact, such as online and mobile communications, to combat depression lockdown effects.