Evaluation of Antigenicity of Components of Tracheal Allotransplant and Effect of Immunosuppressant Regime in a Rodent Model.

Background Tracheal transplantation seems to be the logical step in the process of reconstruction of the trachea following a long-segment resection, which is usually done to treat malignant disease or benign stenosis of the airway caused by a traumatic, congenital, inflammatory, or iatrogenic lesion. Immunosuppression following transplant is essential but not ideal after oncoresection. Methods The tracheal allografts, harvested from Sprague Dawley rats, were implanted in the Wistar strain rat. The harvested tracheal grafts were divided into groups and subgroups, based on the layers of trachea, method of decellularization, and immunosuppression. The antigenicity of different layers of trachea and the effect of various decellularization methods were studied within three time frames, that is, day 3, 9, and 15. Result On structural analysis, the day 3 and day 15 samples showed no meaningful comparison could be made, due to extensive neutrophil infiltration in all three layers. The day 9 tracheal grafts showed loss of epithelium, with no signs of regeneration in most of the allografts. The subepithelial lymphoid infiltration was found to be severe in nonimmunosuppressed allografts. The group in which both inner and outer layers were removed showed moderate-to-severe infiltrate of lymphoid cells in all the allografts, but there was no cartilage loss, irrespective of the method of decellularization. The irradiated specimens retained the cartilage but showed extensive ischemic damage. Conclusion Rat trachea is a good model for tracheal transplant research but not adequately sturdy to sustain mechanical debridement. Irradiation and chemical decellularization eliminates the immune response but causes intense ischemic damage. Out of the three time frames, day 9 seemed to be the best to study the immune response. To substantiate the results obtained in this study, the immunohistochemical study of the allografts is needed to be performed among a larger group of animals.

Indian Subcontinent's First Proximal Forearm Level Double Upper Extremity Transplantation.

Introduction Vascularized composite allotransplantation (VCA) has added another step to the reconstructive ladder, leading to a paradigm shift in the approach toward management of cases of upper limb amputations. In this article, we discuss in detail the technical aspects of proximal forearm level transplantation, as well as the immediate posttransplant monitoring and immunosuppression protocols. Materials and Methods A 24-year-old male victim of an electric injury presented with a bilateral proximal forearm level amputation. After the mandatory preoperative psychiatric and immunological evaluation, the patient underwent a proximal forearm level double upper extremity transplantation. He was then put on a stringent immunosuppression and physical rehabilitative regime. Discussion Conceptually, the proximal forearm level transplantation is significantly different from distal forearm level transplant. This transplant "reestablishes" the "donor extremity length," maintains the normal functional length of the donor muscles, and the functional return happens only after the newly transplanted donor muscles are reinnervated over a period of time. Conclusion As the sequence of surgical repair and associated decision making could be quite confusing for this level of transplantation, it is highly advisable to do mock cadaver surgical dissections in order to standardize the procedure and make the team familiar with it.

Indian Subcontinent's First Bilateral Supracondylar Level Upper Limb Transplantation.

Introduction This is the first case of supracondylar level transplant from the Indian subcontinent, performed for a bilateral below elbow amputee. It has a completely different set of challenges for the transplant team, with a relatively shorter ischemia time window. The technical considerations for the same have been discussed in detail in this article. Materials and Methods The patient was a 19-year-old female who lost her both upper limbs at proximal forearm level due to severe crush injury following a road traffic accident. Insufficient bone length on either side necessitated a supracondylar level transplant. The preoperative workup included detailed clinical evaluation, biochemical, and psychological evaluation. The donor was a young brain-dead, male patient from a hospital, 30 minutes away. The donor and recipient preparations in this case were unique. The recipient's own elbow flexors and extensors were used while the elbow joint was from the donor. The specific challenges we faced during this procedure have been described in detail. Results The transplantation has been a complete technical success, with the patient rehabilitated back to her independent life style. This article describes only the technical considerations. The functional recovery aspect is part of an another soon to be published manuscript. Conclusion Supracondylar level arm-transplant requires a highly coordinated team effort with precise preoperative planning, along with meticulous attention to detail to achieve a successful outcome. In properly selected patients, it could be a life-changing procedure, worth all the effort.

Neuroprotective effect of IDPU (1-(7-imino-3-propyl-2,3-dihydrothiazolo [4,5-d]pyrimidin-6(7H)-yl)urea) in 6-OHDA induced rodent model of hemiparkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative motor disorder characterized by the degeneration of dopaminergic nigrostriatal neurons. Levodopa (l-DOPA) is the most effective therapy for PD, however, PD progression continues with significant side effects in long term, thus necessitating the search for effective therapy that impedes PD progression. PD therapy through non-dopaminergic pathways offers treatment without the risk of extrapyramidal effects. In this regard, earlier, we had reported, a novel compound IDPU with potential adenosine A2A receptor antagonist effect in haloperidol (chronic treatment) induced Parkinson model. In the present study, we extended our investigation towards i) evaluation of IDPU in well-established 6-OHDA induced Parkinson rat model to establish its role in the therapy of PD ii) its function in alleviating the neuronal loss. We carried the IDPU administration (i.p.) in rats for two weeks after establishing 6-OHDA induced unilateral lesions. The behavioral activity, neurochemical alteration, oxidative stress marker and tyrosine hydroxylase positive neurons in substantia nigra were analyzed. The results showed that IDPU significantly reduced motor and non-motor deficits induced by 6-OHDA in the behavioral tasks such as apomorphine, rota rod and force swim test. Furthermore, the results of oxidative stress biomarkers revealed that IDPU successfully modulated oxidative stress associated biomarkers such as MDA, catalase, superoxide dismutase, nitric oxide and reduced glutathione level. Additionally, IDPU significantly elevated intracellular dopamine, decreased glutamate and calcium levels in brain as compared to 6-OHDA alone treated animals which is evocative of its neuroprotective behavior. Thus, the investigations clearly validated IDPU as a potent anti-parkinsonian agent which showed immense capability to protect neurodegeneration.

Electronic interaction between nitrogen atoms in doped graphene.

Many potential applications of graphene require either the possibility of tuning its electronic structure or the addition of reactive sites on its chemically inert basal plane. Among the various strategies proposed to reach these objectives, nitrogen doping, i.e., the incorporation of nitrogen atoms in the carbon lattice, leads in most cases to a globally n-doped material and to the presence of various types of point defects. In this context, the interactions between chemical dopants in graphene have important consequences on the electronic properties of the systems and cannot be neglected when interpreting spectroscopic data or setting up devices. In this report, the structural and electronic properties of complex doping sites in nitrogen-doped graphene have been investigated by means of scanning tunneling microscopy and spectroscopy, supported by density functional theory and tight-binding calculations. In particular, based on combined experimental and simulation works, we have systematically studied the electronic fingerprints of complex doping configurations made of pairs of substitutional nitrogen atoms. Localized bonding states are observed between the Dirac point and the Fermi level in contrast with the unoccupied state associated with single substitutional N atoms. For pyridinic nitrogen sites (i.e., the combination of N atoms with vacancies), a resonant state is observed close to the Dirac energy. This insight into the modifications of electronic structure induced by nitrogen doping in graphene provides us with a fair understanding of complex doping configurations in graphene, as it appears in real samples.

Design and synthesis of (4E)-4-(4-substitutedbenzylideneamino)-3-substituted-2,3-dihydro-2-thioxothiazole-5-carbonitrile as novel A2A receptor antagonists.

Novel 2-thioxothiazole derivatives (6-19) as potential adenosine A2A receptor (A2AR) antagonists were synthesized. The strong interaction of the compounds (6-19) with A2AR in docking study was confirmed by high binding affinity with human A2AR expressed in HEK293T cells using radioligand-binding assay. The compound 19 demonstrated very high selectivity for A2AR as compared to standard A2AR antagonist SCH58261. Decrease in A2AR-coupled release of endogenous cAMP in treated HEK293T cells demonstrated in vitro A2AR antagonist potential of the compound 19. Attenuation in haloperidol-induced impairment (catalepsy) in Swiss albino male mice pre-treated with compound 19 is evocative to explore its prospective in therapy of PD.

Loss of guide wire: a lesson learnt review of literature.

Catheterization of central veins is a routine technique which is widely used in emergency department and medical intensive care units. Seldinger's technique is widely used to place central venous and arterial catheters and is generally considered safe. The technique does have multiple potential risks. Guide wire-related complications are rare but potentially serious. We describe a case of a lost guide wire during central venous catheter (CVC) insertion followed by a review of the literature of this topic. Measures which can be taken to prevent such complications are explained in detail as well as recommended steps to remedy errors should they occur.