A Case Report of Steven Johnson Syndrome

Introduction: In 1922, two doctors, Albert Mason Stevens and Frank Johnson, examined purulent conjunctivitis.” Background: Stevens-Johnson syndrome was named after them as a result of their study. The incidence rate is 7 cases per million populations per year. Case Presentation: Master Yash Ghudam was brought to AVBRH by his parents with chief complaints of fever since 5 days and erythematous lesions all over body since 3 days. History of present illness: Patient was apparently alright 5 days back, and then he started having fever which was of high grade and was not associated with chills and rigor. Patient was treated on OPD basis and the symptoms of an unexplained disease in two young boys, aged 7 and 8, who had "an unusual, generalised eruption of continued fever, inflamed buccal mucosa, and extreme some antibiotic was given, but there was no relief, after 2 days there was ulcers formation inside the mouth for which some ointment and syrup becosule was started. But lesions were increasing. 3 days back the lesions first appeared on chest then got spread to legs and hands. For which patient was admitted in Chandrapur hospital from were the patient was referred to AVBRH for further management. Interventions: The patient was treated the patient was started on intravenous and orally Cortecosteroids, Omnacortil 10mg, Antibiotics- Inj. Ceftriaxone1gm IV 12 hourly [100mg/kg/day], inj. Amikacin 150mg IV 12 hourly [15mg/kg/day], Syp. Mucaine gel 2tsp BD – swish and swallow), Syp. Cital 2.5ml TDS, Tab. Chymoral Forte TDS, Inj. Pantop 20mg IV 24 hourly (1mg/kg/dose). Pandya’s Formula: Syp. Gelusil 5ml, Syp. Benadryl 5ml, Syp. Omnacortil 5ml. Skin allograft: It has been planned. Conclusion: In this study, we mainly focus on medical management and outstanding nursing care helped prevent farther complication. Overall, the patient's reaction was positive, though recovery time from Steven johnson syndrome varies from person to person, taking weeks, months, or even years. However, only a small number of people completely recover, while some have long-term consequences. She took a long time to get back on her feet.

Thermosensitive Polyester Hydrogel for Application of Immunosuppressive Drug Delivery System in Skin Allograft

Tacrolimus (FK506) is a common immunosuppressive drug that is capable of suppressing acute rejection reactions, and is used to treat patients after allotransplantation. A stable and suitable serum concentration of tacrolimus is desirable for better therapeutic effects. However, daily drug administration via oral or injection routes is quite inconvenient and may encounter drug overdose or low patient compliance problems. In this research, our objective was to develop an extended delivery system using a thermosensitive hydrogel of poly ethylene glycol, D,L-lactide (L), and ϵ-caprolactone (CL) block copolymer, mPEG-PLCL, as a drug depot. The formulation of mPEG-PLCL and 0.5% PVP-dissolved tacrolimus was studied and the optimal formulation was obtained. The in vivo data showed that in situ gelling is achieved, a stable and sustained release of the drug within 30 days can be maintained, and the hydrogel was majorly degraded in that period. Moreover, improved allograft survival was achieved. Together, these data imply the potential of the current formulation for immunosuppressive treatments.

Bone marrow mesenchymal stem cell-derived exosomes attenuate the maturation of dendritic cells and reduce the rejection of allogeneic skin transplantation in mice model

Background Bone mesenchymal stem cells (BMSCs)-derived exosomes (B-exos) are attractive for applications in enabling alloantigen tolerance. An in-depth mechanistic understanding of the interaction between B-exos and dendritic cells (DCs) could lead to novel cell-based therapies for allogeneic transplantation. Herein, the potential of a B-exos-based application combined with DCs was explored for inducing allogeneic transplant tolerance. Methods After mixed culture of BMSCs and DCs for 48 hours, DCs from the upper layer were collected to analyze the expression levels of surface markers and mRNAs of inflammation-related cytokines. Then the DCs were co-cultured with B-exo before being collected to detect the mRNA and protein expression levels of indoleamine 2,3-dioxygenase (IDO). The treated DCs from different groups were co-cultured with naïve CD4 + T cells from the mouse spleen. The proliferation of CD4 + T cells and the proportion of CD4 + CD25 + Foxp3 + T cells were analyzed. Finally, the skins of BALB/c mice were transplanted to the back of C57 mice to establish a mouse allogeneic skin transplantation model. Results The coculture of DCs with BMSCs in a trans-well system downregulated the expression of the major histocompatibility complex class II (MHC-II) and CD80/86 costimulatory molecules on DCs, as well as the mRNA expression of interleukin-10 (IL-10), IL-12, and transforming growth factor-β (TGF-β). However, these findings were abolished when treated with GW4869. Moreover, B-exos (5 µg/mL) increased the expression of indoleamine 2,3-dioxygenase (IDO) in DCs treated with lipopolysaccharide (LPS) compared to the control cells. CD4 + CD25 + Foxp3 + T cells increased when cultured with B-exos-exposed DCs, which was attenuated by 1-methyl tryptophan (1MT). Mice recipients injected with B-exos-treated DCs significantly prolonged the skin allograft survival. The allografts showed slight cell infiltration and significantly preserved graft structure. Also, the level of CD4 + CD25 + Foxp3 + T cells was significantly higher in B-exos-exposed DCs recipient animals than that in other groups. Conclusions Taken together, these data suggested that the B-exos suppress the maturation of DCs and increase the expression of IDO, which might shed light on the role of B-exos in inducing alloantigen tolerance.

Procurement and Use of Cryopreserved Total Skin Allograft in Complex Wounds

Cryopreserved total skin allografts are a new therapeutic alternative for the management of complex wounds. Their properties allow them to be classified as a temporary coverage for some patients and as definitive in others. And they can be an alternative option to the use of dermal regeneration templates.

Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model

Antibody-mediated rejection (AMR) represents a major cause of allograft dysfunction and results in allograft failure in solid organ transplantation. Cyclic helix B peptide (CHBP) is a novel erythropoietin-derived peptide that ameliorated renal allograft rejection in a renal transplantation model. However, its effect on AMR remains unknown. This study aimed to investigate the effect of CHBP on AMR using a secondary allogeneic skin transplantation model, which was created by transplanting skin from BALB/c mice to C57BL/6 mice with or without CHBP treatment. A secondary syngeneic skin transplantation model, involving transplantation from C57BL/6 mice to C57BL/6 mice, was also created to act as a control. Skin graft rejection, CD19+ B cell infiltration in the skin allograft, the percentages of splenic plasma cells, germinal center (GC) B cells, and Tfh cells, the serum levels of donor specific antibodies (DSAs), and NF-κB signaling in splenocytes were analyzed. Skin allograft survival was significantly prolonged in the CHBP group compared to the allogeneic group. CHBP treatment also significantly reduced the CD19+ B cell infiltration in the skin allograft, decreased the percentages of splenic plasma cells, GC B cells, and Tfh cells, and ameliorated the increase in the serum DSA level. At a molecular level, CHBP downregulated P100, RelB, and P52 in splenocytes. CHBP prolonged skin allograft survival by inhibiting AMR, which may be mediated by inhibition of NF-κB signaling to suppress B cell immune responses, thereby decreasing the DSA level.

CHBP induces stronger immunosuppressive CD127+ M-MDSC via erythropoietin receptor

Erythropoietin (EPO) is not only an erythropoiesis hormone but also an immune-regulatory cytokine. The receptors of EPO (EPOR)2 and tissue-protective receptor (TPR), mediate EPO’s immune regulation. Our group firstly reported a non-erythropoietic peptide derivant of EPO, cyclic helix B peptide (CHBP), which could inhibit macrophages inflammation and dendritic cells (DCs) maturation. As a kind of innate immune regulatory cell, myeloid-derived suppressor cells (MDSCs) share a common myeloid progenitor with macrophages and DCs. In this study, we investigated the effects on MDSCs differentiation and immunosuppressive function via CHBP induction. CHBP promoted MDSCs differentiate toward M-MDSCs with enhanced immunosuppressive capability. Infusion of CHBP-induced M-MDSCs significantly prolonged murine skin allograft survival compared to its counterpart without CHBP stimulation. In addition, we found CHBP increased the proportion of CD11b+Ly6G−Ly6Chigh CD127+ M-MDSCs, which exerted a stronger immunosuppressive function compared to CD11b+Ly6G−Ly6Chigh CD127− M-MDSCs. In CHBP induced M-MDSCs, we found that EPOR downstream signal proteins Jak2 and STAT3 were upregulated, which had a strong relationship with MDSC function. In addition, CHBP upregulated GATA-binding protein 3 (GATA-3) protein translation level, which was an upstream signal of CD127 and regulator of STAT3. These effects of CHBP could be reversed if Epor was deficient. Our novel findings identified a new subset of M-MDSCs with better immunosuppressive capability, which was induced by the EPOR-mediated Jak2/GATA3/STAT3 pathway. These results are beneficial for CHBP clinical translation and MDSC cell therapy in the future.

Impact of Injection Frequency of Adipose-Derived Stem Cells on Allogeneic Skin Graft Survival Outcomes in Mice

Previous studies indicated that mesenchymal stem cells (MSCs) exhibit immunomodulatory properties in composite tissue allotransplantation. However, due to the high immunogenicity of skin, although the single administration of MSCs improves survival of the skin allotransplant, immune rejection is still inevitable. The aim of our study was to evaluate whether multiple administrations of MSCs would improve immune tolerance in the allogeneic skin graft, compared to that with a single administration in a mouse model. After full-thickness skin allotransplantation on the backs of the mice, the recipient mice were infused with phosphate-buffered saline and isogenic 1.5 × 105/mL adipose-derived stem cells (ADSCs). ADSCs were transplanted into different mice according to the different injection frequencies such as single, once a week, and twice a week. Skin sections were taken on days 7 and 21 post-transplantation in all groups for gene expression and histological studies. ADSCs increased skin allograft survival compared to that in control mice ( P < 0.05). Interleukin-6 and tumor necrosis factor-alpha messenger RNA levels were decreased, and the abundance of lymphocytes, based on immunohistochemistry, was also decreased in ADSC-infused mice ( P < 0.05). However, among the different ADSC injection frequency groups, multiple ADSC infusion did not improve the survival rate and decreased proinflammatory cytokines and lymphocytes, compared to those with the single administration of ADSCs ( P > 0.05). Conversely, the results with single administration were slightly better than those with multiple administrations. Our study demonstrated that ADSCs have the potential for immunomodulation in vivo. However, the results with multiple ADSC administration were not as good as those with single administration, which indicates the complexity of ADSCs in vivo and implying the need for adequate preclinical experimentation.