Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and ...removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose–basic fibroblast growth factor. Administration of 50% oxygen increased oxygen tension in the subcutaneous site to 140 mm Hg, compared to 45 mm Hg under ambient air. In vitro, islets cultured under 140 mm Hg oxygen showed reduced central necrosis and increased insulin release, compared to those maintained in 45 mm Hg oxygen. Six hundred syngeneic islets subcutaneously transplanted into the prevascularized graft bed reversed diabetes when combined with postoperative 50% oxygen inhalation for 3 days, a number comparable to that required for intrahepatic transplantation; in the absence of oxygen treatment, diabetes was not reversed. Thus, we show oxygen inhalation to be a simple and promising approach to successfully establishing subcutaneous islet transplantation.
In conjunction with the creation of a prevascularized graft bed in a Lewis rat model, posttransplant oxygen inhalation significantly improves the efficiency of subcutaneous islet transplantation.
OBJECTIVE: To evaluate the effect of an almond-enriched (high monounsaturated fat, MUFA) or complex carbohydrate-enriched (high carbohydrate) formula-based low-calorie diet (LCD) on anthropometric, ...body composition and metabolic parameters in a weight reduction program. DESIGN: A randomized, prospective 24-week trial in a free-living population evaluating two distinct macronutrient interventions on obesity and metabolic syndrome-related parameters during weight reduction. SUBJECTS: In total, 65 overweight and obese adults (age: 27-79 y, body mass index (BMI): 27-55 kg/m2). INTERVENTION: A formula-based LCD enriched with 84 g/day of almonds (almond-LCD; 39% total fat, 25% MUFA and 32% carbohydrate as percent of dietary energy) or self-selected complex carbohydrates (CHO-LCD; 18% total fat, 5% MUFA and 53% carbohydrate as percent of dietary energy) featuring equivalent calories and protein. MAIN OUTCOME MEASUREMENTS: Various anthropometric, body composition and metabolic parameters at baseline, during and after 24 weeks of dietary intervention. RESULTS: LCD supplementation with almonds, in contrast to complex carbohydrates, was associated with greater reductions in weight/BMI (-18 vs -11%), waist circumference (WC) (-14 vs -9%), fat mass (FM) (-30 vs -20%), total body water (-8 vs -1%) and systolic blood pressure (-11 vs 0%), P=0.0001-0.05. A 62% greater reduction in weight/BMI, 50% greater reduction in WC and 56% greater reduction in FM were observed in the almond-LCD as compared to the CHO-LCD intervention. Ketone levels increased only in the almond-LCD group (+260 vs 0%, P<0.02). High-density lipoprotein cholesterol (HDL-C) increased in the CHO-LCD group and decreased in the almond-LCD group (+15 vs -6%, P=0.05). Glucose, insulin, diastolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and LDL-C to HDL-C ratio decreased significantly to a similar extent in both dietary interventions. Homeostasis model analysis of insulin resistance (HOMA-IR) decreased in both study groups over time (almond-LCD: -66% and CHO-LCD: -35%, P<0.0001). Among subjects with type 1 diabetes, diabetes medication reductions were sustained or further reduced in a greater proportion of almond-LCD as compared to CHO-LCD subjects (96 vs 50%, respectively). CONCLUSION: Our findings suggest that an almond-enriched LCD improves a preponderance of the abnormalities associated with the metabolic syndrome. Both dietary interventions were effective in decreasing body weight beyond the weight loss observed during long-term pharmacological interventions; however, the almond-LCD group experienced a sustained and greater weight reduction for the duration of the 24-week intervention. Almond supplementation of a formula-based LCD is a novel alternative to self-selected complex carbohydrates and has a potential role in reducing the public health implications of obesity.
This review is designed to help the reproductive endocrinologist
integrate his or her professional activity with those of other
disciplines including urology, radiology, neurology, and psychology in
...order to successfully manage all of the inseparable aspects of male
sexual and reproductive functioning. Significant advances in the field
of male sexual physiology and pathophysiology and new methods of
investigation and treatment of male sexual disorders are outlined. The
review synthesizes available data on the following: norms of sexual
organs, aging and sexuality, role of central and peripheral
neurochemicals in each stage of the sexual cycle, role of corporeal
smooth muscles in the hemodynamic control of erection and detumescence,
influence of psychological factors, drugs, and disease on all aspects
of sexual functioning, and use of nocturnal penile tumescence
monitoring, imaging investigations, and neurophysiologic studies in the
diagnostic workup of males with sexual dysfunction. Clinical algorithms
are presented where appropriate. Extensive discussions on newly
developed strategies in psychological and behavioral counseling, drug
therapy, tissue engineering, nonsurgical devices, and surgical
treatments for all forms of sexual disorders are also provided. Lastly,
the effect of sexual dysfunction and its treatment on quality of life
in affected men is addressed, along with recommendations for future
research endeavors.
Organic–inorganic hybrid perovskites (OIHs) are exceptionally promising sector of novel materials for optoelectronic applications. Herein, the OIHs of the formula (NH3)2(CH2)3CuCl4 labeled by C3CuCl ...and (NH3)2(CH2)4CuCl2Br2 labeled by C4CuClBr are prepared by slow evaporation method. The synthesis process is achieved by mixing equimolar ethanolic solutions ratios (1:1) of their basic components (organic/inorganic). Characterizations of these materials using microchemical analysis, energy dispersion X‐ray (EDX) and X‐ray diffraction (XRD) are discussed. The XRD is used to estimate the crystalline size for prepared compounds and found in the range of 38.8 and 48.8 nm for C3CuCl and C4CuClBr, respectively. The vibrational spectra are studied by Fourier transformation infrared spectroscopy (FTIR) and show the major diffraction peaks of compounds and their assignment. UV‐region strong absorption is clarified in the optical properties studied for Cu hybrid, whereas the bandgap energy estimated via Kubelka–Munk equation and found 2.8 and 3.85 eV for C3CuCl and C4CuClBr, respectively.
Cu hybrid perovskites diammonium series (NH3)2(CH2)3CuCl4 and (NH3)2(CH2)4CuCl2Br2 are successfully prepared and characterized to confirm the formation of the novel hybrid perovskites of average crystallite size 38.8 and 48.8 nm, respectively. These optical studies show strong absorption in UV region and energy gap of 2.85 eV ((NH3)2(CH2)3CuCl4) and 3.9 eV ((NH3)2(CH2)4CuCl2Br2).
Standardized assessment of islet quality is imperative for clinical islet transplantation. We have previously shown that the increment in oxygen consumption rate stimulated by glucose (ΔOCRglc) can ...predict in vivo efficacy of islet transplantation in mice. To further evaluate the approach, we studied three factors: islet specificity, islet composition and agreement between results obtained by different groups. Equivalent perifusion systems were set up at the City of Hope and the University of Washington and the values of ΔOCRglc obtained at both institutions were compared. Islet specificity was determined by comparing ΔOCRglc in islet and nonislet tissue. The ΔOCRglc ranged from 0.01 to 0.19 nmol/min/100 islets (n = 14), a wide range in islet quality, but the values obtained by the two centers were similar. The contribution from nonislet impurities was negligible (ΔOCRglc was 0.12 nmol/min/100 islets vs. 0.007 nmol/min/100 nonislet clusters). The ΔOCRglc was statistically independent of percent beta cells, demonstrating that ΔOCRglc is governed more by islet quality than by islet composition. The ΔOCRglc, but not the absolute level of OCR, was predictive of reversal of hyperglycemia in diabetic mice. These demonstrations lay the foundation for testing ΔOCRglc as a measurement of islet quality for human islet transplantation.
Major requirements were met for an islet potency assay (islet specificity, reproducibility by different groups, predictive of transplant success in diabetic mice), laying the foundation for testing its use in assessing islet quality for human islet transplantation.
Aims/hypothesis
TNF-α plays important roles in the pathogenesis of type 1 and type 2 diabetes mellitus. In light of this, we examined the involvement of a pro-apoptotic gene,
BBC3
(also known as
PUMA
...), in TNF-α-mediated beta cell dysfunction and destruction in human islets.
Methods
Human islets were exposed in vitro to TNF-α alone or in combination with IFN-γ. Gene expression was assessed by RT-PCR using a set of single islets. Protein abundance and cellular localisation of BBC3 were assessed by immunoblot and immunohistochemistry. A marginal number of islets were transplanted into diabetic NOD
scid
mice to correlate in vivo islet function with
BBC3
expression.
Results
BBC3
and
IL8
mRNA were upregulated in TNF-α-stimulated islets in a dose-dependent manner and enhanced through addition of IFN-γ, but not upregulated by IFN-γ alone. Immunohistochemistry revealed that TNF-α in combination with IFN-γ upregulated basal BBC3 abundance in the cytoplasm of beta cells along with the perinuclear clustering of mitochondria partially co-localised with BBC3. TNF-α alone did not induce beta cell death, but did abrogate preproinsulin precursor mRNA synthesis in response to high glucose stimulation, which was inversely associated with upregulation of
BBC3
mRNA expression by TNF-α. Higher
BBC3
mRNA expression in islets correlated with decreased graft function in vivo.
Conclusions/interpretation
These results suggest that
BBC3
mRNA can serve as a molecular marker to detect early TNF-α-induced beta cell stress and may help identify islet-protective compounds for the treatment of diabetes.
Induction of hematopoietic chimerism and subsequent donor‐specific immune tolerance via bone marrow transplantation is an ideal approach for islet transplantation to treat type‐1 diabetes. We ...examined the potential of mesenchymal stem cells (MSCs) in the induction of chimerism and islet allograft tolerance without the incidence of graft‐versus‐host disease (GVHD). Streptozotocin‐diabetic rats received a conditioning regimen consisting of antilymphocyte serum and 5 Gy total body irradiation, followed by an intraportal co‐infusion of allogeneic MSCs, bone marrow cells (BMCs) and islets. Although all the recipients rejected the islets initially, half of them developed stable mixed chimerism and donor‐specific immune tolerance, shown by the engraftment of donor skin and second‐set islet transplants and acute rejection of a third‐party skin. The engraftment of the primary islet allografts with stable chimerism was achieved by the addition of a 2‐week peritransplant administration of 15‐deoxyspergualin (DSG). Without MSCs, none of the recipients treated with DSG developed chimerism or reversal of diabetes. GVHD was not observed in any of the recipients infused with MSCs (0/15), whereas it occurred in 4/11 recipients without MSCs. These results indicate a potential use of MSCs for induction of hematopoietic chimerism and subsequent immune tolerance in clinical islet transplantation.
Donor mesenchymal stem cells (MSCs) co‐infused with donor bone marrow cells and islets into the portal vein of diabetic rats treated with non‐myeloablative recipient conditioning regimen helped to induce mixed hematopoietic chimerism and subsequent acceptance of islet allografts.
In the pages that follow,the structure of the crystal, unit cell dimension and complete structure information will be shown by single crystal x-ray diffraction and measuring some physical properties ...of 1D propylene diammonium pentachloro bismuthate (NH3)2(CH2)3BiCl5 organic-inorganic hybrid perovskites (OIHs).Slow evaporation method is used to prepared the synthesis. The process of preparation occurred by mixing ethanolic solution of equimolar ratios (1:1) of its basic components (organic / inorganic). The Bi hybrid crystallized in orthorhombic non centro-symetric Pca21 structure with 8 molecules per unit cell.The unit cell parameters are a = 19.8403 (7) Å, b = 6.3303 (2) Å, c = 19.0314 (7) Å. The average C-C bond lengths are 1.50Å. The average N-C bond lengths are 1.47Å. The connection between organic parts to inorganic part is via hydrogen bond (H. Bond). Raman spectroscopy and also Fourier transform infrared spectroscopy (FTIR) have been used to study the vibrational spectra that shows the main diffraction peaks and their assignment. Diffuse reflectance spectra (DRS) method is used to study the optical properties and show that there is a strong absorption in the UV region for Bi hybrid. Kubelka-Munk equation has been used to calculate the band gap energy and indicates that the band gap for the present investigated hybrid is equals 3.15 eV.
Bone marrow-derived mesenchymal stem cells (MSCs) are known to produce vascular endothelial growth factor. We hypothesize that co-transplantation of MSCs and islets promotes revascularization and ...improves islet graft function.
Lewis rat islets were infused into the liver of streptozotocin-diabetic syngeneic recipients or transplanted under the renal capsule of nonobese diabetic severe combined immunodeficiency (NOD SCID) mice with MSCs isolated from Lewis bone marrow and expanded in culture.
Co-transplantation of 500 islets and 107 MSCs (islet-MSCs) reversed diabetes in all eight recipients, whereas islet-alone transplantation achieved euglycemia in 3 of 10 recipients. With 300 islets, five of nine islet-MSCs and 1 of 10 islets-alone recipients reversed diabetes. Results of intravenous glucose tolerance tests performed on day 56 were significantly better in islet-MSCs than islet-alone recipients. One week after transplantation, well-preserved islet structure and higher number of capillaries were found in the liver of islet-MSCs recipients, whereas islet-alone grafts were fragmented with very few capillaries. Islets showed a similar morphology when transplanted with MSCs in nonobese diabetic severe combined immunodeficiency mice with a significantly higher capillary per beta-cell ratio than that in islet-alone grafts (0.135+/-0.046 vs. 0.052+/-0.028 capillary segments per beta-cell, P<0.01). One week after transplantation, islets were surrounded by MSCs labeled with carboxyfluorescein succinimidyl ester or Qdot nanocrystals, and some labeled MSCs positively stained for vascular endothelial growth factor or von Willebrand factor.
Our results demonstrate the improvement of islet graft morphology and function by co-transplantation with MSCs. This improvement is attributable, at least in part, to the promotion of graft revascularization mediated by MSCs.
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