Engineered islet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes

Pathak, Shiva,Regmi, Shobha,Gupta, Biki,Pham, Tung Thanh,Yong, Chul Soon,Kim, Jong Oh,Yook, Simmyung,Kim, Jae-Ryong,Park, Min Hui,Bae, Young Kyung,Jeong, Jee-Heon Federation of American Societies for Experimental 2017 The FASEB Journal Vol. No.

<P>An alternative route for pancreatic islet transplantation is the subcutaneous space; however, inadequate vascularization in the subcutaneous space limits the availability of oxygen and nutrients to the subcutaneously transplanted islets, which leads to the development of a necrotic core in the islets, thereby causing islet dysfunction. Thus, we aimed to prevent the early apoptosis of pancreatic islets after transplantation into subcutaneous space by preparing islet clusters of appropriate size. We prepared fully functional islet cell clusters (ICCs) by using the hanging-drop technique. We optimized the size of ICCs on the basis of viability and functionality after culture in an hypoxic environment. We transplanted ICCs into the subcutaneous space of diabetic mice and evaluated the viability of the islets at the transplantation site. In an hypoxic environment, ICCs exhibited improved viability and functionality compared with control islets. ICCs, upon transplantation into the hypoxic subcutaneous space of diabetic mice, showed better glycemic control compared with control islets. Live/dead imaging of the islets after retrieval fromthe transplanted area revealed significantly reduced apoptosis in ICCs. Transplantation of ICCsmay be an attractive strategy to prevent islet cell apoptosis that results from nonimmune-mediated physiologic stress at the transplantation site.-Pathak, S., Regmi, S., Gupta, B., Pham, T. T., Yong, C. S., Kim, J. O., Yook, S., Kim, J.-R., Park, M. H., Bae, Y. K., Jeong, J.-H. Engineeredislet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes.</P>

COMMON FIXED POINTS OF COMPATIBLE MAPPINGS OF TYPE(A)

Pathak, H.K.,Kang, S.M. The Youngnam Mathematical Society Korea 1995 East Asian mathematical journal Vol.11 No.1

Immunoisolation of pancreatic islets <i>via</i> thin-layer surface modification

Pathak, Shiva,Pham, Tung Thanh,Jeong, Jee-Heon,Byun, Youngro Elsevier 2019 Journal of controlled release Vol.305 No.-

<P><B>Abstract</B></P> <P>Islet transplantation is an alternative method of replacing exogenous insulin to treat type 1 diabetes. However, transplantation of allo- or xenograft islets causes the activation of host's immune reaction, which leads to the failure of the transplanted grafts. Immunosuppressive-sparing strategies have been introduced to avoid adverse effects associated with a long-term use of the immunosuppressive drugs. In this regard, macro/microencapsulation, surface camouflage, and surface modification with immune-privileged cells have been performed to protect the transplanted islets against instant blood-mediated inflammatory reactions or immune reactions. However, the increased size of the encapsulated islets after transplantation leads to insufficient oxygen and nutrients for the islets, causing most of them to undergo apoptosis. Therefore, recent studies have aimed at reducing the capsule thickness while maintaining immunoprotective ability of encapsulated islets. In this review, we discuss several techniques of thin-layer surface coating of pancreatic islets using a variety of polymers, therapeutic agents (TA), TA-loaded nano or microparticles, and living cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Islet transplantation is a promising method for treating type-1 diabetes. </LI> <LI> Physical and chemical methods have been introduced for surface modification. </LI> <LI> Small molecules, polymers, particles, and cells are used for surface modification. </LI> <LI> Surface modification prolongs islet graft survival in animal models. </LI> <LI> Long-term <I>in vivo</I> effects of surface modification need to be evaluated. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Fast Layout Generation of RF Embedded Passive Circuits Using Mathematical Programming

Pathak, M.,Sung Kyu Lim IEEE 2012 IEEE transactions on components, packaging, and ma Vol.2 No.1

<P>In this paper, we present a methodology for the automatic generation of layout for radio frequency (RF) designs using embedded passives. Our methodology is divided into three steps: 1) pre-layout optimization; 2) placement and routing; and 3) post-layout optimization. We show that our methodology generates layouts with small area and good performance response within a fraction of design time compared with fully manual design effort. We make use of circuit models to represent and optimize the physical layout of the resistance-inductance-capacitance (RLC) components as well as the entire RF circuit that uses them. We perform non-linear mathematical programming-based optimization at various stages of the methodology to achieve high quality layouts. Full wave electromagnetic simulations are kept completely out of the design loop, so our methodology significantly reduces design time. We have used our methodology to successfully generate layouts for large-scale filter circuits.</P>

Delivery of Pancreatic Islets and Single Dose Local Immune Suppression Into Subcutaneous Space Using Injectable Hydrogel Provides Indefinite Survival of the Graft in Mouse Model of Diabetes

Pathak, Shiva,Regmi, Shobha,Pham, Tung Thanh,Yong, Chul Soon,Kim, Jong Oh,Yook, Simmyung,Park, Min-Hui,Bae, Yong Kyung,Jeong, Jee-Heon Wolters Kluwer Health, Inc. All rights reserved. 2018 Transplantation Vol.102 No.7

INTRODUCTION: Pancreatic islet transplantation is a promising technique to treat type 1 diabetes. Long-term survival of the graft is required for a successful islet transplantation. Repeated use of immunosuppressive drugs after organ/cell transplantation often leads to severe adverse effects including nephrotoxicity, hepatotoxicity, and opportunistic infections. Thus, development of a local immunosuppression protocol is necessary to improve the islet graft survival in clinics. MATERIALS AND METHODS: Pancreatic islets from Sprague-Dawley rats were transplanted into the subcutaneous space of B6 mice using injectable hydrogel. Three major groups were prepared for transplantation. (1) Islets transplanted FK506-loaded poly(lactic-co-glycolic acid) microspheres (10 mg/kg), (2) Islets transplanted with clodronate liposomes (6.25 mg/kg), and (3) Islet transplanted with the combination of both immune suppressants. The suspension of islets and immune suppressants in Matrigel was then injected into the subcutaneous space over the flanks of streptozocin-induced diabetic mice. RESULTS: Islets transplanted without any immunosuppression were rejected within two weeks. In contrast, the islets transplanted with the single immunosuppressive regimen of FK506 or clodronate improved survival rate compared with that of the control mice. More interestingly, the graft transplanted using the combination of both immune suppressants survived indefinitely. Immunological studies revealed that the immunosuppressive cocktail inhibited the proliferation of immune cells residing at the peripheral lymph nodes. Interestingly, the systemic immune system of the transplanted mice remained unaffected. Furthermore, histochemical analysis revealed the intact morphology of the islets at the transplanted site when codelivered with the immunosuppressant. DISCUSSION: Antigen presenting cells and T-cells orchestrate the immune rejection cascade. Macrophage depletion by the liposomal clodronate and the inhibition of T-cell activation by FK506 completely blocked the immune rejection cascade in the immune competent mice. The inhibition of immune stimulation in the peripheral lymph nodes improved the islet grafted into the subcutaneous space. Thus, the use of local immune suppression is an effective approach to enhance the survival of the transplanted islets. CONCLUSION: We developed a protocol for the local codelivery of pancreatic islets and immune suppressive agents. Indefinite graft survival was obtained with the use of macrophage depleting agent and T-cell inhibitor. The single dose of local immune suppression during transplantation may avoid toxic effects associated with a long-term use of immune suppressive agents in clinics.National Research Foundation of Korea (NRF) Grant nos: 2015R1A5A2009124 and 2017R1D1A1B03027831. Korea Health Industry Development Institute (KHIDI) Grant no: HI16C1767.

Development of a Highly Effective Protocol using Local Immune Suppression Strategy in Pancreatic Islet Transplantation

Pathak, Shiva,Regmi, Shobha,Pham, Tung Thanh,Yong, Chul Soon,Kim, Jong Oh,Yook, Simmyung,Park, Min-Hui,Bae, Yong Kyung,Jeong, Jee-Heon Wolters Kluwer Health, Inc. All rights reserved. 2018 Transplantation Vol.102 No.7

INTRODUCTION: Pancreatic islet transplantation is a promising technique to treat type 1 diabetes. Long-term survival of the graft is required for a successful islet transplantation. Repeated use of immunosuppressive drugs after organ/cell transplantation often leads to severe adverse effects including nephrotoxicity, hepatotoxicity, and opportunistic infections. Thus, development of a local immunosuppression protocol is necessary to improve the islet graft survival in clinics. MATERIALS AND METHODS: Pancreatic islets from Sprague-Dawley rats were transplanted into the subcutaneous space of B6 mice using injectable hydrogel. Briefly, 1000 islet equivalents were suspended in Matrigel premixed with FK506-loaded poly(lactic-co-glycolic acid) microspheres (10 mg/kg) and clodronate liposomes (6.25 mg/kg) and injected into the subcutaneous space over the flanks of streptozocin-induced diabetic mice. Blood glucose level was monitored using a potable glucometer. RESULTS: Islets transplanted without any immunosuppression were rejected within two weeks. In contrast, the islets transplanted with the immunosuppressive regimen of FK506 and clodronate survived indefinitely. Immunological studies revealed that the immunosuppressive cocktail inhibited the proliferation of immune cells residing at the peripheral lymph nodes. Interestingly, the systemic immune system of the transplanted mice remained unaffected. Furthermore, histochemical analysis revealed the intact morphology of the islets at the transplanted site when codelivered with the immunosuppressant. DISCUSSION: Antigen presenting cells and T-cells orchestrate the immune rejection cascade. Macrophage depletion by the liposomal clodronate and the inhibition of T-cell activation by FK506 completely blocked the immune rejection cascade in the immune competent mice. The inhibition of immune stimulation in the peripheral lymph nodes improved the islet grafted into the subcutaneous space. Thus, the use of local immune suppression is an effective approach to enhance the survival of the transplanted islets. CONCLUSION: We developed a protocol for the local codelivery of pancreatic islets and immune suppressive agents. Indefinite graft survival was obtained with the use of macrophage depleting agent and T-cell inhibitor. The single dose of local immune suppression during transplantation may avoid toxic effects associated with a long-term use of immune suppressive agents in clinics.

CERTAIN RELATIONS FOR MOCK THETA FUNCTIONS OF ORDER EIGHT

Pathak, Maheshwar,Srivastava, Pankaj Korean Mathematical Society 2009 대한수학회논문집 Vol.24 No.4

The aim of the present paper is to establish certain relations for partial mock theta functions and mock theta functions of order eight with other partial mock theta functions and mock theta functions of order two, six, eight and ten respectively.

Narrowband ultraviolet B emitting Gd doped CaAl₂O₄ phosphors – An ESR and photoluminescence study

Pathak, M.S.,Singh, N.,Singh, Vijay,Watanabe, S.,Gundu Rao, T.K.,Seshadri, M.,Lee, Jung-Kul Elsevier 2018 Journal of luminescence Vol.204 No.-

<P><B>Abstract</B></P> <P>Phosphors with the composition Ca<SUB>1-x</SUB>Gd<SUB>x</SUB>Al<SUB>2</SUB>O<SUB>4</SUB> (x = 0.0025–0.09) were synthesized by a simple combustion route in a short time. The formation of the as-prepared combustion products was confirmed by the X-ray diffraction analysis, indicating the formation of a monoclinic phase. The PL spectroscopy assessment shows that with increasing Gd<SUP>3+</SUP> concentration, the ultraviolet emission from Gd<SUP>3+</SUP> at 314 nm (<SUP>6</SUP>P<SUB>7/2</SUB>→<SUP>8</SUP>S<SUB>7/2</SUB>) progressively enhanced. The Gd<SUP>3+</SUP>-doped CaAl<SUB>2</SUB>O<SUB>4</SUB> displays electron spin resonance signals with the effective g values at <I>g</I> ≈ 1.95, 2.9, and 3.7. Additional lines were also observed at the approximate g values of ~2.2 and 5.3. Gd<SUP>3+</SUP> ion located in the distorted surroundings and experiencing relatively strong crystal field, give rise to low field lines. Distorted surroundings in the present system may result from the nearness of the charge compensator oxygen vacancies.</P>

Narrowband ultraviolet B emission from gadolinium activated Y₃Ga₅O₁₂ nano-garnets

Pathak, M.S.,Singh, N.,Singh, Vijay,Watanabe, S.,Rao, T.K.Gundu,Lee, Jung-Kul Elsevier 2018 Materials research bulletin Vol.97 No.-

<P><B>Abstract</B></P> <P>Gadolinium (Gd<SUP>3+</SUP>) doped Y<SUB>3</SUB>Ga<SUB>5</SUB>O<SUB>12</SUB> nanocrystalline garnet was prepared by nitrate-fuel combustion technique that involves organic fuel glycine. Sample characterization was performed by powder X-ray diffraction and scanning electron microscope. Upon ultraviolet light excitation at 273nm, Y<SUB>3</SUB>Ga<SUB>5</SUB>O<SUB>12</SUB>:Gd<SUP>3+</SUP> sample exhibits a sharp narrowband ultraviolet B emission at 311.9nm. The electron spin resonance spectrum of gadolinium doped Y<SUB>3</SUB>Ga<SUB>5</SUB>O<SUB>12</SUB> samples exhibit resonance signals with the effective g values at <I>g</I> ≈2.0, 2.2 and 5.8. These signals are attributed to Gd<SUP>3+</SUP> ion located in distorted surroundings experiencing a relatively strong crystal field.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A narrowband ultraviolet B emitting nano-garnet was synthesized. </LI> <LI> Narrow band centered at 311.9nm, good for phototherapy application. </LI> <LI> EPR results indicate the possible location of the Gd<SUP>3+</SUP> ion. </LI> <LI> Gd<SUP>3+</SUP> ion is likely to be located at the distorted dodecahedral site. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Synthetic Studies and Structural Aspects of some Metallacyclic Derivatives of Titanium (IV) - Better Precursors for Titania

Pathak, Madhvesh,Samuel, Blassan,Tummalapalli, Kiran,Vuppalapati Giri, Prasanth,Bohra, Rakesh,Kim, Kap Jin Trans Tech Publications, Ltd. 2012 Advanced materials research Vol.584 No.-

<P>Titanium(IV) complexes of the type [(acac)2Ti(O-G-O] and [(acac)2Ti(OCH2CH2SH)2] {where G = (CH2)2, CH2CH(CH3), CH2CH(C2H5), CH(CH3)CH(CH3) have been synthesized in high yield by the interaction of the precursor [(acac)2Ti( OR)2] {where R = Pri , Et} with a variety of glycols and thioglycols in 1:1 and 1:2 molar ratios in refluxing benzene under anhydrous condition yield heteroleptic derivatives. On the basis of physico-chemical analyses, a cis-octahedral environment around Ti (IV) is proposed.</P>