PTZ-kindled rat model; evaluation of seizure, hippocampal EGR-1, and Rev-erbα gene regulation, behavioral analysis, and antioxidant capacity of Gum Arabic.

BACKGROUND: Epilepsy is a neurological disease characterized by recurrent seizures, hyperexcitable neurons and various behavioral comorbidities. The electrical charge during seizures depletes the antioxidant defense mechanism in the epileptic brain and increases the oxidative burden. Natural antioxidant compounds are potential therapeutics in the treatment of two major pathologies of epilepsy with their anticonvulsant and anxiolytic effects and can modulate these targets. Gum Arabic is one of the natural plant polysaccharides that is non-toxic and biodegradable. METHODS AND RESULTS: A total of 30 Wistar albino male rats (8-12 weeks, 350-500 g), were randomly divided into 5 groups with 6 animals in each group: 1-Control, 2-Sham (Phosphate buffer saline (PBS)), 3-PTZ, 4-Gum Arabic, 5-PTZ + Gum Arabic. PTZ was administered i.p at 35 mg/kg/day for 11 days. After 48 h, the injection was completed with 75 mg/kg PTZ. Locomotor activity, immobilization, rearing, grooming, eating, and drinking behaviors were recorded with the LABORAS behavior system for 30 min after kindling. Animals were treated with Gum Arabic (2 mg/kg/day, oral gavage) for 10 days. At the end of the period, animal behavior was recorded again. Then the hippocampus tissues were removed. Oxidative parameters (TAS and TOS), early growth response 1 (EGR1) and nuclear receptor subfamily 1 group D member 1 (Rev-erbα) gene expressions and behaviors were analyzed. CONCLUSION: Gum Arabic increased TAS levels (P = 0.000), decreased TOS levels (P = 0.000), and thus exhibited antioxidant properties by reducing oxidative stress burden. EGR1, which was upregulated in the seizure group, was downregulated after treatment (P = 0.000), and Rev-erbα was downregulated in seizure and upregulated after treatment (P = 0.000). Gum arabic may be an antiepileptic and anxiolytic therapeutic in improving epileptic seizures by reducing oxidative stress burden through EGR1 and Rev-erbα.0.

An Investigation of The Effect of Extracellular Vesicles Isolated from Mouse Embryonic Fibroblasts on Wound Healing in an Experimental Diabetic Mouse Model.

This study aimed to investigate the effects of Extracellular Vesicles (EV) secreted from mouse embryonic fibroblasts EV on wound healing of full-thickness skin defect in a diabetic mouse model. The study included both in vitro and in vivo experimental studies 82 mice. In the in vitro stage of the experimental study, hysterectomy was performed on two mice between the 13-14th days of pregnancy and then EV was isolated by cell culturing. VEGF, IL-6, and TNF-α biomarkers were examined in tissue homogenate. Moreover, tissue taken from wound area was also subjected to histopathologic scoring. EV augmented the effect of VEGF. Therefore promoted angiogenesis increases the transport of cells, essential oxygen and nutrients in the wound area. Extracellular vesicles isolated from mouse embryonic fibroblasts have been found to accelerate wound healing in diabetes. The findings obtained from this experimental study indicate that EV isolated from mouse embryonic fibroblasts accelerate the wound healing process in experimentally induced-diabetes in mice.

[Body Contouring after Massive Weight Loss: A Road Map]. / Wiederherstellungsoperationen (WHO's): Eine Übersicht - Straffungsoperationen nach massivem Gewichtsverlust.

Body contouring procedures are the consequent and final step for patients after massive weight loss. These surgical procedures are mainly indicated for functional reasons resulting from extensive excess skin flaps. The current overview serves as an introduction to body contouring strategies without any claim to comprehensiveness. In the following, we describe the general and specific aspects of the respective body contouring procedures. These are in accordance with the guidelines published by the Association of Scientific Medical Societies in Germany (AWMF). This includes principle anatomical functional features, detailed general and specific aspects of a comprehensive history with the respective physical examination. We also describe the documentation and fundamentals of the application for required assumption of costs for hospital care. The main section deals with the principles of the most frequent lifting operations, such as abdominoplasty, brachioplasty, mastopexy, thigh lift etc. We describe the specific aspects of the specific body regions as well as different surgical techniques, with step-by-step instructions and with pre-, intra- and postoperative pictures.

Candida albicans Osteochondromyelitis after Gastroesophageal Surgery: Two Case Reports.

Candida osteochondromyelitis is a rare complication after thoracoabdominal surgery. We herein report two such cases after uncomplicated thoracoabdominal surgery, who presented with chronic postsurgical site infection and fistula. CT scans showed fistulas reaching the costochondral areas of the fifth rib. Inflammatory parameters were not elevated. Both patients were treated successfully after the initiation of systemic antimycotic treatment and surgical debridement. We conclude that C. albicans infections should always be considered in cases of chronic postoperative surgical site infections after thoracoabdominal surgery. Additional risk factors do not need to be present. Appropriate therapy consists of the application of systemic antimycotics and surgical debridement.

Multimodal Evaluation of Functional Nerve Regeneration in Transgender Individuals After Phalloplasty With a Free Radial Forearm Flap.

BACKGROUND: Constructing a sensitive phallus is a key objective in sex affirmation surgery, but still there is a major lack of evidence in outcome analysis of postoperative sensibility of the newly constructed body part. AIM: To evaluate the innervation and sensibility of a forearm free-flap neophallus with nerve coaptation by a broad-spectrum follow-up. METHODS: The phallic sensibility of 20 transgender individuals who underwent phalloplasty with a free radial forearm flap was evaluated by a standardized multimodal approach, examining 5 main sensory modalities. Measurements were performed in defined areas at the phallus and at the unoperated forearm as a control area. Additionally, all patients were asked to complete a questionnaire about their subjective quality of life and ability to orgasm. OUTCOME: This study evaluated the following parameters: perception of pressure (Semmes-Weinstein monofilaments) and vibration (C64 Hz tuning fork), static two-point discrimination, sharp-blunt and hot-cold discrimination at the phallus and the forearm, sum score of calculated life satisfaction, and ability to orgasm. RESULTS: Most of the patients (n = 14) were able to perceive 2 or more sensory modalities tested at the newly constructed phallus. 2 patients did not develop any sensibility. Interestingly, the median values for vibration perception were similar for the phallus and the unoperated forearm. Pressure sensibility was present at the phallus, but less than at the forearm. Moreover, sharp-blunt sensibility was present in 11 patients. In contrast, clear cold-warm discrimination could not be achieved, although the majority of patients detected the cold stimulus. A two-point discrimination of up to 23 mm could not be detected in either body part. 15 patients experienced orgasms without difficulty after 23 months (n = 20 after 54 months). CLINICAL IMPLICATIONS: We observed successful recovery of sensibility at the phalli for the majority of patients, including the preservation of orgasm. STRENGTHS & LIMITATIONS: Our institution is one of the few centers regularly performing phalloplasties in transgender patients, especially preferring the technique of Gottlieb and Levine. This study contributes to the few studies that perform sensory testing at the phallus and is unique in its kind in that it uses a multimodal approach. A limitation of this study is the limited number of cases and the limited validity of vibratory testing. CONCLUSION: Confirming a promising tactile sensibility after phalloplasty with a neurovascular radial forearm flap, the next step would be to identify whether this reinnervation effectively develops due to nerve coaptation or spontaneous sprouting. Küenzlen L, Nasim S, van Neerven S, et al. Multimodal Evaluation of Functional Nerve Regeneration in Transgender Individuals After Phalloplasty With a Free Radial Forearm Flap. J Sex Med 2020;17:1012-1024.

Current surgical approaches in Takayasu's arteritis: a single-centre experience.

OBJECTIVES: We investigated cardiovascular surgical interventions in a group of patients with Takayasu's arteritis (TAK) diagnosed and followed by a single centre. METHODS: . Twenty patients with TAK (5 males, 15 females, mean current age: 38.1±10.7) who were operated for a broad spectrum of cardiovascular diseases ranging from coronary heart disease to coeliac stenosis or aneurysm between July 2008 and April 2016 were studied. One patient underwent operation related to aneurysm of ascending aorta and aortic insufficiency, 2 patients had operations for both coronary arteries originating from aortic arch, 6 patients for only arteries originating from aortic arch, 1 patient for both carotid and infra-inguinal artery, 5 patients for aorta-iliac or femoral revascularisation, 5 patients for renal artery and/or coeliac or superior mesenteric artery revascularisations. Three of these interventions were endarterectomy and patch plasty. RESULTS: The mean time between diagnosis and surgical intervention was 6.1±3.1 years (range: 3 months-12 years). A total of 4/32 (12.5%) grafts were occluded during the follow up period of mean 39.2±24.6 months. Secondary interventions like cross-femoral, or graft to superficial femoral artery bypasses were needed in 2 patients who underwent aorta-bifemoral bypasses to keep patency. There was no operative mortality. We did not observe any anastomotic aneurysm. One patient died due to graft infection 3 months after the operation. Stroke occurred in 2 patients who underwent re-vascularisations of the arteries originating from aortic arch. CONCLUSIONS: In our series, we have a relatively good midterm patency rates in patients with TAK and did not observe any anastomotic pseudoaneurysm. Stroke developed in 2 patients and mortality occurred in one patient due to the graft infection 3 months after the operation. In patients with limited carotid or aorta-iliac stenosis, chance for endarterectomy should be evaluated. Well-controlled disease activity with intensive medical treatment and multi-disciplinary approach could be associated with a favourable long-term outcome.

Phalloplasty in Female-to-Male Transsexuals by Gottlieb and Levine's Free Radial Forearm Flap Technique-A Long-Term Single-Center Experience Over More than Two Decades.

BACKGROUND: The free radial forearm flap phalloplasty is the most utilized method for penile reconstruction. Among the techniques described in the literature, evidence for the flap design after Gottlieb and Levine is poor. METHODS: From January 1993 until December 2015, 402 phalloplasties were performed in our clinic. Among the 247 free radial forearm flap phalloplasties, 232 free radial forearm flap phalloplasties were performed after Gottlieb and Levine in 229 patients. Operation and patient-specific characteristics were evaluated. RESULTS: This study presents the highest number of free radial forearm flap phalloplasties after Gottlieb and Levine. The rate of total flap failure was 3%; 46% of the patients were heavy smokers. Urinary fistulae and strictures are common. The revision rate for urinary fistulae and/or strictures was 1.3 per patient. The number of postoperative complications, such as bleeding (14.2%), thrombosis of the flap requiring revision (11.2%), or delayed wound healing (16.8%) was considering the high rate of nicotine abuse (45.9%) reasonable. CONCLUSION: The free radial forearm phalloplasty in the design by Gottlieb and Levine is well established at our institution and has proven safe and reliable since 1993. The operative results are satisfactory for both patients and surgeons even in the presence of relevant comorbidities and heavy smoking. We acknowledge the long ordeal and psychological pressure that our patients suffer from, before presenting in our outpatient clinic.

Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration.

Spontaneous Reinnervation of Deep Inferior Epigastric Perforator Flaps after Delayed Breast Reconstruction.

BACKGROUND: The spontaneous reinnervation of free flaps, such as deep inferior epigastric perforator (DIEP) flaps, is not fully understood, and few publications have investigated this issue. The aim of this study was to examine spontaneous reinnervation following breast reconstruction with autologous DIEP flaps without an additional nerve transfer. METHODS: In a retrospective clinical study, 18 female patients were investigated for a mean of 49.59 months (range, 12-88 months) following breast reconstruction with a unilateral DIEP flap. Five sensory modalities were tested: pressure perception, dynamic two-point discrimination, sharp-blunt discrimination, hot and cold discrimination, and vibration perception threshold (VPT). The measurements were performed on the reconstructed breast, flap surrounding transition zone, healthy contralateral breast, and the donor site. For a more precise analysis all breasts have been divided into five different segments (mediocranial, laterocranial, mediocaudal, laterocaudal, and reconstructed nipple-areola complex, if present). Additionally, tissue oxygen saturation and tissue hemoglobin were measured by laser Doppler spectroscopy. RESULTS: Spontaneous reinnervation of at least one modality tested was observed in all DIEP flaps (n = 18). This sensitive recovery increases over the postoperative period. The maximum difference between the controls and DIEP flaps was observed in cold perception, whereas the least difference was observed in the VPT. Regarding the different segments, we observed better sensitive recovery in the cranial parts of the DIEP flaps and the transition zone. CONCLUSION: This study provides certain predictions for patients and surgeons, when and to which extent spontaneous reinnervation can be expected.

Differences in degradation behavior of two non-cross-linked collagen barrier membranes: an in vitro and in vivo study.

OBJECTIVES: Collagen barrier membranes are used in guided bone regeneration/guided tissue regeneration because of their excellent bio- and cytocompatibility. However, they are considered to have limitations in clinical outcome because of rapid and unpredictable degradation profiles. The aim of this study was to investigate the degradation behavior of two porcine-based, non-cross-linked collagen membranes in vitro and in vivo. MATERIALS AND METHODS: Remaix™ (RX; Matricel GmbH, Herzogenrath, Germany) and Bio-Gide® (BG; Geistlich Pharma AG, Wolhusen, Switzerland) membranes were characterized by testing mechanical strength, denaturation temperature, enzymatic degradation and hydroxyproline content in vitro (n = 5 up to 16). Thereafter, both membranes were implanted subcutaneously in rats (n = 20) for up to 20 weeks to investigate tissue compatibility with respect to membrane thickness. RESULTS: BG contained a significant higher hydroxyproline content compared with RX, but RX showed a higher stress at break (dry: 11.4 (SD 2.9) vs. 5.5 (SD 1.5) N/mm(2)), higher suture retention (wet: 5.6 (SD 1.3) vs. 2.7 (SD 0.7) N), increased denaturation temperature (55.1 (SD 1) vs. 49.4 (SD 0.6)°C) and an almost twofold reduction in degradation rate (15.6% (SEM 1.3)/h vs. 24.8% (SEM 2.9)/h) in vitro. In the rat model, both membranes showed excellent tissue compatibility without signs of inflammatory reactions. Shortly after implantation, RX and BG showed moderate infiltration of mononuclear cells that appeared not to be influenced by the surface texture of the membranes. In the histomorphometric analysis, both membranes showed significant different thickness over the 20 weeks period (P = 0.0002). Although the thickness remained almost stable during the first 9 weeks after implantation, after 20 weeks, the thickness of RX decreased only slightly, whereas BG showed a thickness loss of around 50% and stronger degradation than RX. Therefore, the higher stability of RX against biodegradation found in vitro was confirmed in the animal study. CONCLUSION: This study shows differences in the biodegradation characteristics of two non-cross-linked collagen membranes in vitro and in vivo. Whether the higher stability of RX is of clinical relevance should be analyzed in future clinical investigations.

Monte Carlo calculated photon interaction coefficients for several body tissues.

Absorption of energy in body tissues because of radiation interactions may induce harmful outcomes such as cancer and hereditary effects due to a variety of damages in the integrity and activity of the cells. This study presents Monte Carlo calculated $\boldsymbol{\mu} /\boldsymbol{\rho}$, ${\boldsymbol{\mu}}_{\boldsymbol{en}}/\boldsymbol{\rho}$ and ${\boldsymbol{\mu}}_{\boldsymbol{tr}}/\boldsymbol{\rho}$ values of some common tissues and organs found in the human body (namely, adipose tissue, blood, bone-cortical, brain-grey/white matter, breast tissue, eye lens, lung tissue, muscle-skeletal, ovary, soft tissue and testes) as well as water for comparison purposes. The simulation model involves a monoenergetic point source producing a pencil beam where, depending on the parameter under study, particle flux, energy flux or absorbed dose from photon interactions are scored in the range of 10 keV to 20 MeV energy. The simulations were performed using the Monte Carlo package MCNP6.1 and provided $\boldsymbol{\mu} /\boldsymbol{\rho}$, ${\boldsymbol{\mu}}_{\boldsymbol{en}}/\boldsymbol{\rho}$ and ${\boldsymbol{\mu}}_{\boldsymbol{tr}}/\boldsymbol{\rho}$ values. The data produced in this study were compared with theoretical photon attenuation data from the XMUDAT database and demonstrated good agreement. The results, which are based on a simple model geometry and pure elemental compositions, indicate that this approach can be applied to evaluate $\boldsymbol{\mu} /\boldsymbol{\rho}$, ${\boldsymbol{\mu}}_{\boldsymbol{en}}/\boldsymbol{\rho}$ and ${\boldsymbol{\mu}}_{\boldsymbol{tr}}/\boldsymbol{\rho}$ in a broad energy range for any element, compound or mixture.

Effect of Bovine Lactoferrin Treatment on Iron Homeostasis and Gene Expression Changes in Multiple Organ Dysfunctions During Wound Healing Process in Rats.

BACKGROUND: Injury systemically disrupts the homeostatic balance and can cause organ failure. LF mediates both iron-dependent and iron-independent mechanisms, and the role of LF in regulating iron homeostasis is vital in terms of metabolism. OBJECTIVES: In this study, we evaluated the organ-level effect and gene expression change of bLf in the cutaneous repair process. MATERIALS AND METHODS: An excisional full-thickness skin defect (FTSD) wound model was created in male Sprague Dawley rats (180-250 g) (n = 48) fed a high-fat diet (HFD) and the PHGPx, SLC7A11 and SLC40A1 genes and iron metabolism were evaluated. The animals were randomly divided into 6 groups: 1- Control, 2- bLf (200 mg/kg/day, oral), 3- FTSD (12 mm in diameter, dorsal), 4- HFD + bLf, 5- HFD + FTSD, 6- HFD + FTSD + bLf. Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Gene expression analysis was performed with qPCR. RESULTS: Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Prussian blue reactions were detected in the kidney. PHPGx and SLC7A11 genes in kidney and liver tissue were statistically significant (P < 0.05) except for the SLC40A1 gene (P > 0.05). Expression changes of the three genes were not statistically significant in analyses of rat intestinal tissue (P = 0.057). CONCLUSION: In the organ-level ferroptotic damage mechanism triggered by wound formation. BLf controls the expression of three genes and manages iron deposition in these three tissues. In addition, it suppressed the increase in iron that would drive the cell to ferroptosis and anemia caused by inflammation, thereby eliminating iron deposition in the tissues.

Comparative analysis of VenaBlock and VenaSeal Systems for catheter-guided endovenous cyanoacrylate closure in treating chronic venous insufficiency of the lower extremity: effectiveness and feasibility.

Cyanoacrylate adhesive closure (CAC) systems are widely used to treat varicose veins. In terms of efficacy and safety, these nonthermal, non-tumescent methods are noninferior to endovenous thermal ablation techniques. However, no published studies have compared products that use CAC systems. VenaSeal® (Medtronic, Santa Rosa, CA, USA) and VenaBlock® (Invamed) are the most commonly used CAC-based products worldwide. This study aimed to focus on the efficacy of these two commonly used products, with little emphasis on safety. Published full-text articles on the VenaBlock® and VenaSeal® systems were searched. Data for each product were evaluated by comparing them with each other in terms of effectiveness. In total, 1882 extremities from 11 studies using VenaBlock® and 524 extremities from eight studies using VenaSeal® were included and compared. Both devices were effective, and their cumulative recanalization-free survival rates were similar (P=0.188) at the 6-, 12-, 24-, 36-, and 60-month follow-ups. Both products improved the venous clinical severity score (VCSS) and quality of life (QoL) scores. VenaBlock® and VenaSeal® are effective in terms of cumulative recanalization-free survival rates, and no significant difference was found between the two groups (P=0.188). Both significantly improve the VCSS and QoL scores. CAC is feasible for the treatment of varicose veins.

Investigation into effects of tocilizumab and epoetin beta in rats with experimental sciatic nerve injury model.

OBJECTIVE: To investigate the effects of tocilizumab (TCZ), epoetin beta (EPO), and their combination on nerve regeneration in a sciatic nerve injury model. MATERIALS AND METHOD: Male Sprague-Dawley rats were divided into (-) negative control, sham, TCZ, EPO ((+) positive control), and TCZ+EPO groups. The TCZ group received TCZ (8 mg/kg intraperitoneal) immediately after surgery. On day 14th, the EPO group received EPO (5000 IU/kg, intraperitoneal); the TCZ+EPO group received TCZ (8 mg/kg, intraperitoneal), EPO (5000 IU/kg, intraperitoneal), and TCZ (8 mg/kg, intraperitoneal) post-surgery. Motor and sensory functions were assessed pre and post-surgery. Lipid peroxidation and oxidative stress parameters were evaluated biochemically in the serum, and sciatic nerve tissue was evaluated histopathologically using haematoxylin-Eosin and Masson trichrome staining. CONCLUSIONS: TCZ and EPO decreased nerve injury effects by increasing motor and sensory conduction velocities of the sciatic nerve. Biochemically, TCZ and EPO significantly increased Superoxide Dismutase, Catalase, and Glutathione peroxidase 4 levels while decreasing Lipid Peroxidation levels (p=0.001). Histopathologically, neuronal degeneration following nerve injury was decreased in the groups receiving TCZ and EPO (p=0.001). EPO and TCZ attenuate the adverse effects of nerve injury. However, the TCZ+EPO treatment favoured biochemical activities over tissue and functional activities. This has been confirmed functionally, biochemically, and histopathologically.

Evaluation of mucin-1, nuclear factor κB, and hemoglobin A1c levels in obese and non-obese individuals.

OBJECTIVE: Obesity is a chronic multisystem disease associated with increased morbidity and mortality. Obesity, which is a complex, multifactorial, and heterogeneous condition, is thought to result from the interaction of environmental, physiological, and genetic factors. In this study, the relationship between serum levels of hemoglobin A1c, mucin-1, and nuclear factor κB in obese and healthy cohorts was evaluated along with biochemical and gene expressions and with demographic and clinical covariates, and their effects on obesity were evaluated. METHODS: This case-control study included a total of 80 individuals, 40 healthy controls and 40 obesity patients, consisting of female and male aged between 18 and 63 years. Hemoglobin A1c, mucin-1, and nuclear factor κB levels were determined by ELISA in serum samples obtained from patients. In addition, aspartate aminotransferase, alanine transaminase, low density lipoprotein, and glucose values were measured. The gene expressions of the same markers were analyzed by quantitative real-time polymerase chain reaction, and their regulation status was defined. RESULTS: Serum levels of hemoglobin A1c, mucin-1, and nuclear factor κB were found to be high in obese individuals (p<0.05). The gene expression of these serum markers was found to be upregulated. Of the anthropometric measurements, waist circumference and body mass index were correlated with both serum markers and gene expressions (p<0.05). CONCLUSION: In addition to the known association of hemoglobin A1c and nuclear factor κB with obesity, serum levels of mucin-1 as well as upregulation of genes point to its modifier effect on obesity. These parameters can be the powerful markers in the diagnosis of obesity.

Guidelines for management of actual or suspected inadvertent intra-arterial injection of sclerosants.

BACKGROUND: Inadvertent intra-arterial injection of sclerosants is an uncommon adverse event of both ultrasound-guided and direct vision sclerotherapy. This complication can result in significant tissue or limb loss and significant long-term morbidity. OBJECTIVES: To provide recommendations for diagnosis and immediate management of an unintentional intra-arterial injection of sclerosing agents. METHODS: An international and multidisciplinary expert panel representing the endorsing societies and relevant specialities reviewed the published biomedical, scientific and legal literature and developed the consensus-based recommendations. RESULTS: Actual and suspected cases of an intra-arterial sclerosant injection should be immediately transferred to a facility with a vascular/interventional unit. Digital Subtraction Angiography (DSA) is the key investigation to confirm the diagnosis and help select the appropriate intra-arterial therapy for tissue ischaemia. Emergency endovascular intervention will be required to manage the risk of major limb ischaemia. This includes intra-arterial administration of vasodilators to reduce vasospasm, and anticoagulants and thrombolytic agents to mitigate thrombosis. Mechanical thrombectomy, other endovascular interventions and even open surgery may be required. Lumbar sympathetic block may be considered but has a high risk of bleeding. Systemic anti-inflammatory agents, anticoagulants, and platelet inhibitors and modifiers would complement the intra-arterial endovascular procedures. For risk of minor ischaemia, systemic oral anti-inflammatory agents, anticoagulants, vasodilators and antiplatelet treatments are recommended. CONCLUSION: Inadvertent intra-arterial injection is an adverse event of both ultrasound-guided and direct vision sclerotherapy. Medical practitioners performing sclerotherapy must ensure completion of a course of formal training (specialty or subspecialty training, or equivalent recognition) in the management of venous and lymphatic disorders (phlebology), and be personally proficient in the use of duplex ultrasound in vascular (both arterial and venous) applications, to diagnose and provide image guidance to venous procedure. Expertise in diagnosis and immediate management of an intra-arterial injection is essential for all practitioners performing sclerotherapy.

Characterization of novel nitrite-based nitric oxide generating delivery systems for topical dermal application.

Topical application of nitric oxide (NO) has been shown to exert beneficial effects in the therapy of chronic wounds, impaired microcirculation, and skin infections. Nitrite acidified by ascorbic acid has been widely used in many studies as NO-donor system, unfortunately with inflammatory and toxic effects on the treated skin due to unregulated excessive NO generation, low pH and possible toxic side products. Here we describe an essentially modified nitrite based NO generating system that avoid the mentioned unwanted side effects on human skin by using a pH-stable acetate/acetic acid buffer with a skin neutral pH of 5.5 and sodium ascorbate. In order to overcome the shortcoming of lower NO yields due to the higher pH-value and low nitrite concentrations, we have determined additionally the influence of copper ions. To investigate the influence of different NO release and penetration kinetics on NO-induced toxicity, we have developed a fibroblast assay using cell culture plates with gas permeable bottoms. The results show clearly that the donor system can achieve a sustained NO generation without generating high peaks. Furthermore, the presence of Cu(2+) ions enhances manifold NO generation of pH/ascorbate-induced nitrite decomposition, a mechanism comprising the reduction of Cu(2+) ions to Cu(1+) by ascorbate. Finally, we have found that apart from the NO dose the NO release kinetics had a significant influence of cell toxicity. Thus, application of comparable NO amounts within a time interval of 600s led to the development of variable cell toxicities, which predominantly depended on the NO concentration values generated in the first 200s. In summary, we here describe a novel nitrite-based NO-donor system that can provide well defined NO concentrations at skin neutral pH-values for side effect poor topical dermal application, i.e. in the therapy of chronic wounds and impaired microcirculation.

Ferroptotic Potency of ISM1 Expression in the Drug-Induced Alzheimer's Disease-Like Phenotype Under the Influence of Betulin.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by two main pathological mechanisms, mostly hyperphosphorylated tau and amyloid-ß toxicity. Although many studies focus on these basic mechanisms, ferroptosis draws attention as an important pathway responsible for neurodegeneration in AD. There is no definitive treatment for AD but alternative phytochemicals to drugs come into prominence. Betulin is usually obtained from the birch tree. It is an abundant triterpene and has a high antioxidant capacity. Isthmin-1 (ISM1) is a secreted adipokine. OBJECTIVE: In this study, we investigated the potential treatment of AD in the ferroptosis-ISM1-betulin triangle. METHODS: For this, we created an AD model with okadaic acid (200 ng/kg)) in 36 Wistar albino male rats and treated with betulin (20 mg/kg/day, i.p). We evaluated ISM1 gene expression, iron accumulation, and total oxidative metabolism parameters (TAS, TOS, OSI) in hippocampal tissue. We analyzed cognitive recovery in AD with Morris Water Maze Test and general locomotor activity, explore, and anti-anxiolytic effect with Open Field Test. RESULTS: We compared the obtained data with metabolic and genetic results. In conclusion, betulin may have a role in neuronal ferroptotic mechanisms by reducing iron accumulation by ISM1 regulation. CONCLUSIONS: Betulin may have a role in neuronal ferroptotic mechanisms by reducing iron accumulation by ISM1 regulation. Although this study suggests the corrective effect of betulin and ISM1 on cognitive gain and anxiety, it is the first study to show the total antioxidant capacity of betulin in AD.

A personalized Monte Carlo study of tumor and critical organ doses for trans-arterial radioembolization patients.

Trans-arterial radioembolization (TARE) is an intra-arterial treatment method for liver malignancies. In this procedure, the therapeutic tumor dose is significant for predicting the treatment effectiveness while the dose absorbed in an organ at risk provides an understanding of its tolerance to radiation. This study proposes a Monte Carlo (MC) approach for determining absorbed organ doses for patients undergoing TARE treatment. The technique is based on the use of a voxel-based partial body model generated for each patient from his/her anatomical image data to represent the critical body structures more realistically. These structures are first segmented from image slices to create an image block which is then incorporated into a radiation transport package (MCNP6.2) to perform MC simulations. When used along with the parameters specific to a patient's treatment, such as lung-shunt factor, tumor-to-normal liver ratio, fractional uptakes, and administered activity, this approach allowed more accurate simulation of radiation interactions and hence provided absorbed doses specific to a TARE patient. The MC method also calculated the absorbed doses in organs or tissues that were close to target tissues for which the Medical Internal Radiation Dose Committee (MIRD) formalism makes no predictions. MIRD calculations were found to overestimate the absorbed doses by as much as 11% in lungs, 5% in liver, and 20% in tumor volumes. This raises concerns about the treatment's efficacy when estimating the correct activity to be administered to a patient. When each patient simulation was repeated with a90Y source spectrum to reflect the distribution of varying beta energies, the liver and the lungs were observed to receive relatively lower doses than those obtained with monoenergetic beta particles. Thus, it can be stated that the approach adopted in this study offers a more precise model of the patient's critical tissues and serves as a personalized dosimetric tool for TARE treatment planning.

Histopathological efficacy of tacrolimus in an experimental head trauma study.

BACKGROUND: This study aimed to investigate the protective effect of tacrolimus (FK506), an immunosuppressive agent, on secondary brain damage in rats with experimental head trauma. METHODS: 40 Sprague-Dawley rats, aged 10-12 weeks and weighing 250-350 g, were used without gender selection. The subjects that were divided into five groups of 8 rats per group (sham control, negative control, positive control, vehicle control, and treatment) were sacrificed 1 month after head trauma was induced under appropriate conditions, their brains were then removed en bloc and evaluated histopathologically. Secondary brain injury was evaluated with the immunoreactive score (IRS) after Glial Fibrillary Acid Protein staining of gliosis that would occur in brain tissue. RESULTS: The evaluation of the histopathological IRS values of all groups showed significant statistical differences between all groups. The pairwise group comparison revealed the highest increase in IRS value in the treatment group (p<0.05), with no statistical significance despite the increase in the negative control, positive control, and vehicle control groups. The sham group had the lowest rate of severe histopathological reaction score. CONCLUSION: It was observed that the group treated with FK506 had a statistically significant increase in gliosis in the traumatic area compared to the other control groups. This shows that FK506 cannot prevent and even increase gliosis by a mechanism that has not yet been clarified. In conclusion, it is obvious that the FK506 immunosuppressive agent does not reduce post-traumatic brain injury; on the contrary, it increases gliosis.