The Effects of the Steroids 5-Androstenediol and Dehydroepiandrosterone and Their Synthetic Derivatives on the Viability of K562, HeLa, and Wi-38 Cells and the Luminol-Stimulated Chemiluminescence of Peripheral Blood Mononuclear Cells from Healthy Volunteers.

In order to evaluate the role of substituents at 3-C and 17-C in the cytotoxic and cytoprotective actions of DHEA and 5-AED molecules, their derivatives were synthesized by esterification using the corresponding acid anhydrides or acid chlorides. As a result, seven compounds were obtained: four DHEA derivatives (DHEA 3-propionate, DHEA 3-butanoate, DHEA 3-acetate, DHEA 3-methylsulfonate) and three 5-AED derivatives (5-AED 3-butanoate, 5-AED 3,17-dipropionate, 5-AED 3,17-dibutanoate). All of these compounds showed micromolar cytotoxic activity toward HeLa and K562 human cancer cells. The maximum cytostatic effect during long-term incubation for five days with HeLa and K562 cells was demonstrated by the propionic esters of the steroids: DHEA 3-propionate and 5-AED 3,17-dipropionate. These compounds stimulated the growth of normal Wi-38 cells by 30-50%, which indicates their cytoprotective properties toward noncancerous cells. The synthesized steroid derivatives exhibited antioxidant activity by reducing the production of reactive oxygen species (ROS) by peripheral blood mononuclear cells from healthy volunteers, as demonstrated in a luminol-stimulated chemiluminescence assay. The highest antioxidant effects were shown for the propionate ester of the steroid DHEA. DHEA 3-propionate inhibited luminol-stimulated chemiluminescence by 73% compared to the control, DHEA, which inhibited it only by 15%. These data show the promise of propionic substituents at 3-C and 17-C in steroid molecules for the creation of immunostimulatory and cytoprotective substances with antioxidant properties.

The art of ignoring others' work among academics: A guessing game model of scholarly information search.

Why do scholars pay attention to some works, but not others? This article explores a theoretical model in which scholars search the literature to make sure that their findings are new to their immediate audience. Within the present model, individuals easily disregard literatures of which their audiences are probably unaware. Institutionally organized audiences thus serve as enforcers of the information search. Their members may tacitly collaborate in maintaining unawareness of intellectual developments outside of their common attention space. This model allows us to explain phenomena on which earlier models fail - for example why academics sometimes ignore apparently relevant sources of information or how groups of scholars turn into bubbles, censoring information about findings made in the outside world.

Autologous Genetically Enriched Leucoconcentrate in the Preventive and Acute Phases of Stroke Treatment in a Mini-Pig Model.

The natural limitations of regeneration in the CNS are major problems for the treatment of neurological disorders, including ischaemic brain strokes. Among the approaches being actively developed to inhibit post-ischaemic negative consequences is the delivery of therapeutic genes encoding neuroprotective molecules to the brain. Unfortunately, there are currently no proven and available medicines that contain recombinant human genes for the treatment of ischaemic cerebral stroke. Of particular interest is the development of treatments for patients at risk of ischaemic stroke. In the present study, we propose a proof of concept for the use of an autologous, genetically enriched leucoconcentrate temporally secreting recombinant vascular endothelial growth factor (VEGF), glial-cell-line-derived neurotrophic factor (GDNF) and the neural cell adhesion molecule (NCAM) for the treatment of stroke. In a mini-pig ischaemic stroke model, genetically enriched leucoconcentrate was infused 4 h after surgery (gene therapy in acute phase) or 2 days before stroke modelling (preventive gene therapy). On day 21, after the stroke modelling, the post-ischaemic brain recovery was examined by morphologic and immunofluorescence analysis. The benefits of treating a stroke with genetically enriched leucoconcentrate both for preventive purposes and in the acute phase were confirmed by an improved performance in behavioural tests, higher preservation of brain tissue and positive post-ischaemic brain remodelling in the peri-infarct area. These results suggest that the employment of autologous leucocytes enabling the temporary production of the recombinant therapeutic molecules to correct the pathological process in the CNS may be one of the breakthrough approaches in gene therapy.

Changes in Number and Antibacterial Activity of Silver Nanoparticles on the Surface of Suture Materials during Cyclic Freezing.

This article presents the results of the 10-fold cyclic freezing (-37.0 °C) and thawing (0.0 °C) effect on the number and size range of silver nanoparticles (AgNPs). AgNPs were obtained by the cavitation-diffusion photochemical reduction method and their sorption on the fiber surface of various suture materials, perlon, silk, and catgut, was studied. The distribution of nanoparticles of different diameters before and after the application of the cyclic freezing/thawing processes for each type of fibers studied was determined using electron microscopy. In general, the present study demonstrates the effectiveness of using the technique of 10-fold cyclic freezing. It is applicable to increase the absolute amount of AgNPs on the surface of the suture material with a simultaneous decrease in the size dispersion. It was also found that the application of the developed technique leads to the overwhelming predominance of nanoparticles with 1 to 15 nm diameter on all the investigated fibers. In addition, it was shown that after the application of the freeze/thaw method, the antibacterial activity of silk and catgut suture materials with AgNPs was significantly higher than before their treatment by cyclic freezing.

New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation.

The contemporary strategy for spinal cord injury (SCI) therapy aims to combine multiple approaches to control pathogenic mechanisms of neurodegeneration and stimulate neuroregeneration. In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) combined with supra- and sub-lesional epidural electrical stimulation (EES) was tested on mini-pigs similar in morpho-physiological scale to humans. The complex analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed: better performance in behavioural and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite EES on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients.

Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats.

Resistance to antibacterial therapy requires the discovery of new methods for the treatment of infectious diseases. Lactoferrin (LTF) is a well-known naïve first-line defense protein. In the present study, we suggested the use of an adenoviral vector (Ad5) carrying the human gene encoding LTF for direct and cell-mediated gene therapy of maxillofacial area phlegmon in rats. Abscesses were developed by injection of the purulent peritoneal exudate in the molar region of the medial surface of the mandible. At 3-4 days after phlegmon maturation, all rats received ceftriaxone and afterward were subcutaneously injected around the phlegmon with: (1) Ad5 carrying reporter gfp gene encoding green fluorescent protein (Ad5-GFP control group), (2) Ad5 carrying LTF gene (Ad5-LTF group), (3) human umbilical cord blood mononuclear cells (UCBC) transduced with Ad5-GFP (UCBC + Ad5-GFP group), and (4) UCBC transduced with Ad5-LTF (UCBC + Ad5-LTF group). Control rats developed symptoms considered to be related to systemic inflammation and were euthanized at 4-5 days from the beginning of the treatment. Rats from therapeutic groups demonstrated wound healing and recovery from the fifth to seventh day based on the type of therapy. Histological investigation of cervical lymph nodes revealed purulent lymphadenitis in control rats and activated lymphatic tissue in rats from the UCBC + Ad5-LTF group. Our results propose that both approaches of LTF gene delivery are efficient for maxillofacial area phlegmon recovery in rats. However, earlier wound healing and better outcomes in cervical lymph node remodeling in the UCBC + Ad5-LTF group, as well as the lack of direct exposure of the viral vector to the organism, which may cause toxic and immunogenic effects, suggest the benefit of cell-mediated gene therapy.

Combination of epidural electrical stimulation with ex vivo triple gene therapy for spinal cord injury: a proof of principle study.

Despite emerging contemporary biotechnological methods such as gene- and stem cell-based therapy, there are no clinically established therapeutic strategies for neural regeneration after spinal cord injury. Our previous studies have demonstrated that transplantation of genetically engineered human umbilical cord blood mononuclear cells producing three recombinant therapeutic molecules, including vascular endothelial growth factor (VEGF), glial cell-line derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) can improve morpho-functional recovery of injured spinal cord in rats and mini-pigs. To investigate the efficacy of human umbilical cord blood mononuclear cells-mediated triple-gene therapy combined with epidural electrical stimulation in the treatment of spinal cord injury, in this study, rats with moderate spinal cord contusion injury were intrathecally infused with human umbilical cord blood mononuclear cells expressing recombinant genes VEGF165, GDNF, NCAM1 at 4 hours after spinal cord injury. Three days after injury, epidural stimulations were given simultaneously above the lesion site at C5 (to stimulate the cervical network related to forelimb functions) and below the lesion site at L2 (to activate the central pattern generators) every other day for 4 weeks. Rats subjected to the combined treatment showed a limited functional improvement of the knee joint, high preservation of muscle fiber area in tibialis anterior muscle and increased H/M ratio in gastrocnemius muscle 30 days after spinal cord injury. However, beneficial cellular outcomes such as reduced apoptosis and increased sparing of the gray and white matters, and enhanced expression of heat shock and synaptic proteins were found in rats with spinal cord injury subjected to the combined epidural electrical stimulation with gene therapy. This study presents the first proof of principle study of combination of the multisite epidural electrical stimulation with ex vivo triple gene therapy (VEGF, GDNF and NCAM) for treatment of spinal cord injury in rat models. The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee (approval No. 2.20.02.18) on February 20, 2018.

Gene-modified leucoconcentrate for personalized ex vivo gene therapy in a mini pig model of moderate spinal cord injury.

We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy for neurodegenerative diseases, neurotrauma, and stroke. In this study, using a mini pig model of spinal cord injury, we proposed for the first time the use of gene-modified leucoconcentrate prepared from peripheral blood in the plastic blood bag for personalized ex vivo gene therapy. Leucoconcentrate obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector (Ad5/35F) that carried an enhanced green fluorescent protein (EGFP) reporter gene in the plastic blood bag. The day after blood donation, the mini pigs were subjected to moderate SCI and four hours post-surgery they were intravenously autoinfused with gene-modified leucoconcentrate. A week after gene-modified leucoconcentrate therapy, fluorescent microscopy revealed EGFP-expressing leucocytes in spinal cord at the site of contusion injury. In the spleen the groups of EGFP-positive cells located in the lymphoid follicles were observed. In vitro flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by leucocytes. Thus, the efficacy of leucocytes transduction in the plastic blood bag and their migratory potential suggest their use for temporary production of recombinant biologically active molecules to correct certain pathological conditions. This paper presents a proof-of-concept of simple, safe and effective approach for personalized ex vivo gene therapy based on gene-modified leucoconcentrate autoinfusion. The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee (approval No. 5) on May 27, 2014.

Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment.

The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.

Combined Supra- and Sub-Lesional Epidural Electrical Stimulation for Restoration of the Motor Functions after Spinal Cord Injury in Mini Pigs.

This study evaluates the effect of combined epidural electrical stimulation (EES) applied above (C5) and below (L2) the spinal cord injury (SCI) at T8-9 combined with motor training on the restoration of sensorimotor function in mini pigs. The motor evoked potentials (MEP) induced by EES applied at C5 and L2 levels were recorded in soleus muscles before and two weeks after SCI. EES treatment started two weeks after SCI and continued for 6 weeks led to improvement in multiple metrics, including behavioral, electrophysiological, and joint kinematics outcomes. In control animals after SCI a multiphasic M-response was observed during M/H-response testing, while animals received EES-enable training demonstrated the restoration of the M-response and H-reflex, although at a lower amplitude. The joint kinematic and assessment with Porcine Thoracic Injury Behavior scale (PTIBS) motor recovery scale demonstrated improvement in animals that received EES-enable training compared to animals with no treatment. The positive effect of two-level (cervical and lumbar) epidural electrical stimulation on functional restoration in mini pigs following spinal cord contusion injury in mini pigs could be related with facilitation of spinal circuitry at both levels and activation of multisegmental coordination. This approach can be taken as a basis for the future development of neuromodulation and neurorehabilitation therapy for patients with spinal cord injury.

Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat.

Currently, the main fundamental and clinical interest for stroke therapy is focused on developing a neuroprotective treatment of a penumbra region within the therapeutic window. The development of treatments for ischemic stroke in at-risk patients is of particular interest. Preventive gene therapy may significantly reduce the negative consequences of ischemia-induced brain injury. In the present study, we suggest the approach of preventive gene therapy for stroke. Adenoviral vectors carrying genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF) and neural cell adhesion molecule (NCAM) or gene engineered umbilical cord blood mononuclear cells (UCB-MC) overexpressing recombinant VEGF, GDNF, and NCAM were intrathecally injected before distal occlusion of the middle cerebral artery in rats. Post-ischemic brain recovery was investigated 21 days after stroke modelling. Morphometric and immunofluorescent analysis revealed a reduction of infarction volume accompanied with a lower number of apoptotic cells and decreased expression of Hsp70 in the peri-infarct region in gene-treated animals. The lower immunopositive areas for astrocytes and microglial cells markers, higher number of oligodendrocytes and increased expression of synaptic proteins suggest the inhibition of astrogliosis, supporting the corresponding myelination and functional recovery of neurons in animals receiving preventive gene therapy. In this study, for the first time, we provide evidence of the beneficial effects of preventive triple gene therapy by an adenoviral- or UCB-MC-mediated intrathecal simultaneous delivery combination of vegf165, gdnf, and ncam1 on the preservation and recovery of the brain in rats with subsequent modelling of stroke.

Interplay of Pyrrolidine Units with Homo/Hetero Chirality and CF3-Aryl Substituents on Secondary Structures of ß-Proline Tripeptides in Solution.

All possible variants of ß-proline functionalized tripeptides consisting of homo/hetero chiral monomeric all-cis 5-arylpyrrolidine-2,4-dicarboxylate units were synthesized for the first time by a nonpeptidic coupling method based on 1,3-dipolar cycloaddition chemistry of azomethine ylides. Secondary structures of ß-proline tripeptides in solution were determined using the NMR spectroscopy data. o-(Trifluoromethyl)phenyl substituent contributes to stereoselectivity of 1,3-dipolar cycloaddition and structural features of ß-proline tripeptides. A ß-proline CF3-tripeptide with alternating absolute chirality between adjacent pyrrolidine units mimics natural PPII helix secondary structure.

Crystal structure of 4-[(1R,2S,5R)-2-isopropyl-5-methyl-cyclo-hex-yl] 2-methyl (2S,4S,5R)-1-[(2S,3R,5R)-5-meth-oxy-carbonyl-2-(2-methyl-phen-yl)pyrrolidine-3-carbon-yl]-5-(2-methyl-phen-yl)pyrrolidine-2,4-di-carboxyl-ate.

The title compound, C38H50N2O7, represents a chiral ß-proline dipeptide. Corresponding stereogenic centres of constituting pyrrolidine units have opposite absolute configurations. The central amide fragment is planar within 0.1 Šand adopts a Z configuration along the N-CO bond. In the crystal, the hydrogen atoms of the methyl-ene groups form several short inter-molecular C-H⋯O contacts with the carbonyl oxygen atoms of an adjacent mol-ecule. The only active amino hydrogen atom is not involved in hydrogen bonding.

Triple-Gene Therapy for Stroke: A Proof-of-Concept in Vivo Study in Rats.

Natural brain repair after stroke is extremely limited, and current therapeutic options are even more scarce with no clinical break-through in sight. Despite restricted regeneration in the central nervous system, we have previously proved that human umbilical cord blood mono-nuclear cells (UCB-MC) transduced with adenoviral vectors carrying genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) successfully rescued neurons in amyotrophic lateral sclerosis and spinal cord injury. This proof-of-principle project was aimed at evaluating the beneficial effects of the same triple-gene approach in stroke. Rats subjected to distal occlusion of the middle cerebral artery were treated intrathecally with a combination of these genes either directly or using our cell-based (UCB-MC) approach. Various techniques and markers were employed to evaluate brain injury and subsequent recovery after treatment. Brain repair was most prominent when therapeutic genes were delivered via adenoviral vector- or UCB-MC-mediated approach. Remodeling of brain cortex in the stroke area was confirmed by reduction of infarct volume and attenuated neural cell death, depletion of astrocytes and microglial cells, and increase in the number of oligodendroglial cells and synaptic proteins expression. These results imply that intrathecal injection of genetically engineered UCB-MC over-expressing therapeutic molecules (VEGF, GDNF, and NCAM) following cerebral blood vessel occlusion might represent a novel avenue for future research into treating stroke.

Spinal Cord Molecular and Cellular Changes Induced by Adenoviral Vector- and Cell-Mediated Triple Gene Therapy after Severe Contusion.

The gene therapy has been successful in treatment of spinal cord injury (SCI) in several animal models, although it still remains unavailable for clinical practice. Surprisingly, regardless the fact that multiple reports showed motor recovery with gene therapy, little is known about molecular and cellular changes in the post-traumatic spinal cord following viral vector- or cell-mediated gene therapy. In this study we evaluated the therapeutic efficacy and changes in spinal cord after treatment with the genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG), and neuronal cell adhesion molecule (NCAM) applied using both approaches. Therapeutic genes were used for viral vector- and cell-mediated gene therapy in two combinations: (1) VEGF+GDNF+NCAM and (2) VEGF+ANG+NCAM. For direct gene therapy adenoviral vectors based on serotype 5 (Ad5) were injected intrathecally and for cell-mediated gene delivery human umbilical cord blood mononuclear cells (UCB-MC) were simultaneously transduced with three Ad5 vectors and injected intrathecally 4 h after the SCI. The efficacy of both treatments was confirmed by improvement in behavioral (BBB) test. Molecular and cellular changes following post-traumatic recovery were evaluated with immunofluorescent staining using antibodies against the functional markers of motorneurons (Hsp27, synaptophysin, PSD95), astrocytes (GFAP, vimentin), oligodendrocytes (Olig2, NG2, Cx47) and microglial cells (Iba1). Our results suggest that both approaches with intrathecal delivery of therapeutic genes may support functional recovery of post-traumatic spinal cord via lowering the stress (down regulation of Hsp25) and enhancing the synaptic plasticity (up regulation of PSD95 and synaptophysin), supporting oligodendrocyte proliferation (up regulation of NG2) and myelination (up regulation of Olig2 and Cx47), modulating astrogliosis by reducing number of astrocytes (down regulation of GFAP and vimetin) and microglial cells (down regulation of Iba1).

Evaluation of direct and cell-mediated triple-gene therapy in spinal cord injury in rats.

Current treatment options for spinal cord injury (SCI) are scarce. One of the most promising innovative approaches include gene-therapy, however no single gene has so far been shown to be of clinical relevance. This study investigates the efficacy of various combinations of vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG) and neuronal cell adhesion molecule (NCAM) in rats. Multiple therapeutic genes were administered intrathecally either via adenoviral vectors or by using genetically modified human umbilical cord blood mononuclear cells (hUCBMCs). Following the induction of SCI, serial assessment of cord regeneration was performed, including morphometric analysis of gray and white matters, electrophysiology and behavioral test. The therapeutic gene combinations VEGF+GDNF+NCAM and VEGF+ANG+NCAM had positive outcomes on spinal cord regeneration, with enhanced recovery seen by the cell-based approach when compared to direct gene therapy. The efficacy of the genes and the delivery methods are discussed in this paper, recommending their potential use in SCI.

A pilot study of cell-mediated gene therapy for spinal cord injury in mini pigs.

Currently, in clinical practice there is no efficient way to overcome the sequences of neurodegeneration after spinal cord traumatic injury. Using a new experimental model of spinal cord contusion injury on miniature pigs, we proposed to deliver therapeutic genes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF) and neural cell adhesion molecule (NCAM) to the damaged area, using umbilical cord blood mononuclear cells (UCBC). In this study, genetically engineered UCBC (2×106 cells in 200 ml of saline) were injected intrathecally to mini-pigs 10days after SCI. Control and experimental mini pigs were observed for 60days after surgery. Histological, electrophysiological, and clinical evaluation demonstrated significant improvement in animal treated with genetically engineered UCBCs. Difference in recovery of the somatosensory evoked potentials and in histological findings in control and treated animals support the positive effect of the gene-cell constriction for recovery after spinal cord injury. Results of this study suggest that transplantation of UCBCs simultaneously transduced with three recombinant adenoviruses Ad5-VEGF, Ad5-GDNF and Ad5-NCAM represent a novel potentially successful approach for treatment of spinal cord injury.

Tandem Delivery of Multiple Therapeutic Genes Using Umbilical Cord Blood Cells Improves Symptomatic Outcomes in ALS.

Current treatment options of chronic, progressive degenerative neuropsychiatric conditions offer only marginal efficacy, and there is no therapy which arrests or even reverses these diseases. Interest in genetic engineering and cell-based approaches have constantly been increasing, although most of them so far proved to be fruitless or at best provided very slight clinical benefit. In the light of the highly complex patho-mechanisms of these maladies, the failure of drugs aimed at targeting single molecules is not surprising. In order to improve their effectiveness, the role of a unique triple-combination gene therapy was investigated in this study. Intravenous injection of human umbilical cord blood mononuclear cell (hUCBMC) cotransduced with adenoviral vectors expressing vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) resulted in prominent increase of life span and performance in behavioral tests in amyotrophic lateral sclerosis (ALS). Expression of the recombinant genes in hUCBMCs was confirmed as soon as 5 days after transduction by RT-PCR, and cells were detectable for as long as 1 month after grafting in lumbar spinal cord by immunofluorescent staining. Xenotransplantation of cells into mice blood without any immunosuppression demonstrated a high level of hUCBMCs homing and survivability in the central nervous system (CNS), most conspicuously in the spinal cord, but not in the spleen or liver. This study confirms an increased addressed homing and notable survivability of triple-transfected cells in lumbar spinal cord, yielding a remarkably enhanced therapeutic potential of hUCBMCs overexpressing neurotrophic factors.

Instrumental Mechanoreceptoric Palpation in Gastrointestinal Surgery.

BACKGROUND AND AIMS: Small gastric or colorectal tumours can be visually undetectable during laparoscopic surgeries, and available methods still do not provide a 100% localisation rate. Thus, new methods for further improvements in tumour localisation are highly desirable. In this study, we evaluated the usage of the Medical Tactile Endosurgical Complex (MTEC) in gastrointestinal surgery for localisation of tumours. The MTEC provides the possibility of instrumental mechanoreceptoric palpation, which serves as an analogue of conventional manual palpation. METHODS: Ninety-six elective surgeries were performed, including 48 open surgeries, 43 laparoscopies, and 5 robot-assisted surgeries. The 20 mm version of the MTEC tactile mechanoreceptor was used in open surgeries, and the 10 mm version in laparoscopic and robot-assisted surgeries. RESULTS: The mean time of instrumental mechanoreceptoric palpation was 3 minutes 12 seconds for open surgeries, which constituted the early stage of the learning curve, and 3 minutes 34 seconds for laparoscopic surgeries. No side effects or postoperative complications related to instrumental mechanoreceptoric palpation were observed, and this procedure provided data sufficient for tumour localisation in more than 95% of cases. CONCLUSION: Instrumental mechanoreceptoric palpation performed using MTEC is a simple, safe, and reliable method for tumour localisation in gastrointestinal laparoscopic surgery.

Instrumental tactile diagnostics in robot-assisted surgery.

BACKGROUND: Robotic surgery has gained wide acceptance due to minimizing trauma in patients. However, the lack of tactile feedback is an essential limiting factor for the further expansion. In robotic surgery, feedback related to touch is currently kinesthetic, and it is mainly aimed at the minimization of force applied to tissues and organs. Design and implementation of diagnostic tactile feedback is still an open problem. We hypothesized that a sufficient tactile feedback in robot-assisted surgery can be provided by utilization of Medical Tactile Endosurgical Complex (MTEC), which is a novel specialized tool that is already commercially available in the Russian Federation. MTEC allows registration of tactile images by a mechanoreceptor, real-time visualization of these images, and reproduction of images via a tactile display. MATERIALS AND METHODS: Nine elective surgeries were performed with da Vinci™ robotic system. An assistant performed tactile examination through an additional port under the guidance of a surgeon during revision of tissues. The operating surgeon sensed registered tactile data using a tactile display, and the assistant inspected the visualization of tactile data. First, surgeries where lesion boundaries were visually detectable were performed. The goal was to promote cooperation between the surgeon and the assistant and to train them in perception of the tactile feedback. Then, instrumental tactile diagnostics was utilized in case of visually undetectable boundaries. RESULTS: In robot-assisted surgeries where lesion boundaries were not visually detectable, instrumental tactile diagnostics performed using MTEC provided valid identification and localization of lesions. The results of instrumental tactile diagnostics were concordant with the results of intraoperative ultrasound examination. However, in certain cases, for example, thoracoscopy, ultrasound examination is inapplicable, while MTEC-based tactile diagnostics can be efficiently utilized. CONCLUSION: The study proved that MTEC can be efficiently used in robot-assisted surgery allowing correct localization of visually undetectable lesions and visually undetectable boundaries of pathological changes of tissues.