Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy.

Development of versatile nanoplatforms that simultaneously integrate therapeutic and diagnostic features for stimuli-responsive delivery to tumors remains a great challenge. In this work, we report a novel intelligent redox-responsive hybrid nanosystem composed of MnO2 nanoparticles (NPs) and doxorubicin (DOX) co-loaded within poly(N-vinylcaprolactam) nanogels (PVCL NGs) for magnetic resonance (MR) imaging-guided and ultrasound-targeted microbubble destruction (UTMD)-promoted tumor chemotherapy. Methods: PVCL NGs were first synthesized via a precipitation polymerization method, decorated with amines using ethylenediamine, and loaded with MnO2 NPs through oxidation with permanganate and DOX via physical encapsulation and Mn-N coordination bonding. The as-prepared DOX/MnO2@PVCL NGs were well characterized. UTMD-promoted cellular uptake and therapeutic efficacy of the hybrid NGs were assessed in vitro, and a xenografted tumor model was used to test the NGs for MR imaging and UTMD-promoted tumor therapy in vivo.Results: The as-prepared DOX/MnO2@PVCL NGs with a size of 106.8 nm display excellent colloidal stability, favorable biocompatibility, and redox-responsiveness to the reductive intracellular environment and tumor tissues having a relatively high glutathione (GSH) concentration that can trigger the synchronous release of Mn2+ for enhanced T1-weighted MR imaging and DOX for enhanced cancer chemotherapy. Moreover, the DOX/MnO2@PVCL NGs upon the UTMD-promotion exhibit a significantly enhanced tumor growth inhibition effect toward subcutaneous B16 melanoma owing to the UTMD-improved cellular internalization and tumor penetration. Conclusion: Our work thereby proposes a promising theranostic nanoplatform for stimuli-responsive T1-weighted MR imaging-guided tumor chemotherapy.

[Bidirectional knotless barbed sutures during primary total knee arthroplasty: effective solution or new problem?] / Primenenie dvunapravlennykh nitei s nasechkami dlia nepreryvnogo bezuzlovogo shva v pervichnoi artroplastike kolennogo sustava.

THE HYPOTHESIS OF THE STUDY: The use of bidirectional knotless barbed sutures for closure of capsule and subcutaneous fat tissue in primary total knee arthroplasty (TKA) is safe and time-saving. MATERIAL AND METHODS: 302 patients with end-stage osteoarthritis scheduled for primary non-complex TKA were randomly divided into two prospective groups: in group I (N=102) the capsule of the knee joint and subcutaneous fat tissues were closed by continuous braided suture while in group II (N=200) by bidirectional knotless barbed sutures. The skin in both groups was closed by non-absorbable monofilament polycaproamide uninterrupted suture. RESULTS: The time of the surgery was significantly shorter in group II (65,25±11,9 min) than in group I (72,5±14,7 min) (p<0.05). The volume of hidden blood loss was similar in both groups. The number of patients with superficial infection during the first two week after surgery did not differ significantly (1,9% (I) and 1% (II)): they all healed successfully after skin debridement and additional closure. There were no cases of deep periprosthetic infection (PPI). At 3-month follow-up no difference found regarding pain level and knee function (Knee Society Score). CONCLUSION: The use of bidirectional knotless barbed sutures in TKA reduces the time of surgery, does not affect the volume of hidden blood loss or PPI occurrence.

Sistemas transportadores de fármacos basados en el polímero poly(e-caprolactona) para el tratamiento del cáncer / Drug delivery systems based on poly(e-caprolactone) for cancer treatment

Chemotherapy agents have little or no specificity over cancer cells, resulting in lowtherapeutic concentrations at the tumor site (a consequence of a broad systemic distribution),and severe side effects. With the aim of avoiding cancer therapy failure, several approachessuch as design of new anticancer drugs, chemical engineering of conventional drugs anddevelopment of drug delivery systems have been proposed. The objective is to enhance druglocalization at the tumor region (by controlling its biodistribution profile) and, therefore, toincrease the anti-tumor efficacy (even in multi-drug resistant tumors), while reducingsystemic side effects. One of the most promising approaches to the problem is thedevelopment of drug nanocarriers based on the polymer poly(e-caprolactone). In this reviewwe will focus our attention on these polymeric colloids, particularly on the most significantcharacteristics and formulation procedures, and on their use as nanoplatforms for the deliveryof chemotherapy agents to the tumor site. Furthermore, the most recent in vitro and in vivoinvestigations on the subject are extensively reviewed(AU

Thermosensitive micelles based on folate-conjugated poly(N-vinylcaprolactam)-block-poly(ethylene glycol) for tumor-targeted drug delivery.

Thermosensitive PNVCL-b-PEG block copolymer coupled with folic acid was prepared as an anti-cancer drug carrier. This polymer self-assembled into stable micelles in aqueous solutions at above 33 degrees C. At 37 degrees C, the release profile of PNVCL-b-PEG-FA micelles showed a slower and more controlled release of the entrapped 5-FU than that at 25 degrees C. The blank and 5-FU-loaded PNVCL-b-PEG-FA micelles did not induce remarkable cytotoxicity against the EA.hy 926 human endothelial cell line; however, 5-FU-loaded PNVCL-b-PEG-FA micelles showed a cytotoxicity effect against 4T1 mouse mammary carcinoma cells due to the availability of loaded anti-cancer drugs delivered to the inside of the cancer cells by the folate-receptor-mediated endocytosis process.

[Morphology of tissue reactions around implants after combined surgical repair of the abdominal wall]. / Morfologiia tkanevykh reaktsii vokrug implantatov, ispol'zuemykh dlia kombinirovannoi plastiki briushnoi stenki.

Tissue reactions to titanium-nickelide and polypropylen and caprone implants used in surgical treatment of anterior aldomen wall hernias were studied in experiment. Digital density of leukocytes, fibroblasts, vessels, thickness of the capsule were studied. Pronounced inflammatory reaction was observed on day 3 which attenuated on day 14 in case of titanium nickelide and on day 30-60 in case of polypropylene and caprone. Fibroplastic processes start in the first group after 7 days while in the second group only after 30 days of the experiment. Thickness of the capsule around titanium-nickelide was 2-3 times less than around polypropylene and caprone. Thus, titanium-nickelide material is biologically more inert than caprone and polypropylen which are widely used in surgery of hernias.

[A comparative assessment of modern suture materials in stomach resection]. / Sravnitel'naia otsenka sovremennykh shovnykh materialov pri rezektsii zheludka.

Results of stomach resection by Bilrot-II in 30 experimental animals and 369 patients with gastric and duodenal ulcers were analyzed. Gastroenteroanastomoses were created with various sutures: capron, polysorb, titanium clips. Pneumopression, bacteriologic and morphologic examinations of anastomosis, fibroesophagogastroduodeno- and intestinoscopy, peripheral computed electrogastroenterography were used. It was revealed that mechanical suture with titanium clips was the best. Polysorb thread is inferior in tissue reaction to mechanical suture but superior to capron. Use of polysorb reduced rate of complications in immediate postoperative period 4 times. Taking into consideration high cost of suture devices it is reasonable to introduce polysorb in practice of abdominal surgery.

The Lichtenstein open tension-free inguinal hernia repair using a new prosthetic mesh-Bulgarian irresorbable ampoxen.

The routine use of mesh for repair of inguinal hernia has been popularized by Lichtenstein and coworkers. We adopted this technique and performed it widely using a mesh unknown in the Western world. Ampoxen [multifilamented polycaproamide, impregnated with 5-Nitro-8-Hydroxyquinolinum (Nitroxolinum, DCI), MEDICA, SA, Sandanski, Bulgaria] was discovered in 1975 and proved to be an excellent prosthetic material for replacement of attenuated or destroyed abdominal wall; furthermore, this mesh is very cheap and became widely applicable in our country. This report describes our experience with the first 846 adult inguinal hernia repairs under local anesthesia using Ampoxen. All 846 patients had excellent results, without recurrence. There were nine wound infections (1.1%), 16 testicular oedemas (1.9%), no seromata and no deaths. In no patient was the prosthetic mesh removed. There were no complications related to the use of Ampoxen; this mesh is permanent, has a great degree of fibrous tissue reaction, and wide spectrum antimicrobic activity. We advocate the Lichtenstein technique using irresorbable mesh (particularly Ampoxen) for all adult groin hernias except Types 1 and 2 (according to Nyhus' classification), and for all adult recurrent groin hernias.

[A stabilizing plastic repair method for reconstruction in extensive complete defects of the chest wall]. / Plastichno-stabilizirasht metod za rekonstruktsiia pri obshirni pulni defekti na grudnata stena.

Experience is recorded with the application of a new operative method for combined plastic-stabilizing reconstruction of the thoracic wall in complete defects larger than 8-10/10 cm (greater than 80 cm2). The method consists of covering in layers the defect with Ampoxen, auto-rib and skin-muscle flap. Nine patients were operated: 2 with recurrent tumors of the mammary gland, 2 with metastatic thoracic wall tumors, 2 with osteoradionecrosis. 2 with osteomyelitis of 3-4 ribs and 1 with wide communicating bronchopleurocutaneous fistulas. The advantages of the method are pointed out: permanent stabilization of the thoracic wall, provision of optimal biological terrain for postoperative radiotherapy, applicability in purulent-necrotic defects. The method is described in detail, as well as the results in the operated patients for a period from 1 to 4 years.

[A new method for the surgical treatment of urinary incontinence following surgery of the prostate]. / Nov metod na operativno lechenie na inkontinentsiiata na urinata sled operatsii na prostatnata zhleza.

A new method is reported for operative treatment of urine incontinence, following transversal adenomectomy and transurethral resection of the prostate gland. The operative technique is described in detail. Its basic point is placing of a small "Ampoxen" ball over the urethral bulbus. Disappearance of the incontinence after such an operation is due both to the compression on the bulbar part of the urethra and to the formation of connective tissue, which proliferates into the sheet being placed. Twelve patients from 62 to 75 years of age were treated in this way. In 10 of them the immediate and the late results are considered very good. Incontinence disappeared until the 3. day after removing the indwelling catheter. In the other two patients the result is considered satisfactory. The encouraging results make the authors prefer the method which they suggest for postoperative urine incontinence.