Bio-reactive advanced glycation endproducts (AGE) alter the structure and function of molecules in biological systems and increase oxidative stress. These adverse effects of both exogenous and endogenously derived AGE have been implicated in the pathogenesis of diabetic complications and changes associated with ageing including atherosclerosis, renal, eye and neurological disease. Specific AGE receptors and nonreceptor mechanisms contribute to these processes but also assist in the removal and degradation of AGE. The final disposal of AGE depends on renal clearance. Promising pharmacologic strategies to prevent AGE formation, reduce AGE toxicity, and/or inactivate AGE are under investigation.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2796.2002.00932.x

Diabetes and advanced glycation endproducts.

Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation endproducts.

Dehydroepiandrosterone (DHEA) and its sulfated metabolite DHEA-S are endogenous hormones secreted by the adrenal cortex in response to adrenocorticotrophin (ACTH). Much has been published regarding potential effects on various systems. Despite the identification of DHEA and DHEA-S more than 50 years ago, there is still considerable controversy as to their biological significance. This article reviews the metabolism and physiology of DHEA and DHEA-S, the influence of age and gender on concentrations, and changes in endogenous concentrations associated with disease states and other factors, including diet and exercise. This article is unique in that it also summarizes the influence of drugs on DHEA and DHEA-S concentrations, as well as concentrations of DHEA and DHEA-S observed after the administration of DHEA by various routes. Sections of the article specifically address DHEA and DHEA-S concentrations as they relate to stress, central nervous system function and psychiatric disorders, insulin sensitivity, immunological function, and cardiovascular disorders.

DHEA and DHEA-S: a review.

https://www.kidney-international.org/article/S0085-2538(15)48302-4/pdf

Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat.

The incidence of diabetes, especially type 2 diabetes, is increasing at an alarming rate assuming epidemic proportions (1). Worldwide, 124 million people had diabetes by 1997, although an estimated 221 million people will have diabetes by the year 2010 (1).

https://care.diabetesjournals.org/content/diacare/29/6/1420.full.pdf

Diabetes and Advanced Glycoxidation End-Products

As microelectronic integration trends move toward ultrafine density flip chips and bumpless interconnect systems, it is necessary to develop a low cost, ultra-high density, low-damage and low-temperature interconnect technology. To satisfy this requirement, a new bonding method, the surface activated bonding (SAB), was introduced. In this process, the bonding pads on chips and bumps on substrates are first cleaned by Ar plasma or atom beam irradiation, precisely aligned with an accuracy of less than /spl plusmn/0.5 /spl mu/m. Then they are bonded directly to each other only by contact at room temperature or low temperature in a newly developed flip chip bonder. This procedure, which enables the bonding in an inert ambient atmosphere of N/sub 2,/ under atmospheric pressure, cuts down the bonding condition requirements and decreased the process cost. Some preliminary experiments have led to Au-Au and Au-Cu direct bonding, demonstrating the performance of the new bonding system.

Surface activated bonding for new flip chip and bumpless interconnect systems

A 21-yr-old female with hyperthyroidism is described. Though her serum-free T3 was 17.8 pmol/L and free T4 was 60.2 pmol/L, TSH was as high as 10.7 mU/L. TRH stimulated an increase in TSH from 10.7-91.7 mU/L. T3 administration in gradually increasing doses of 100, 200, and 400 mg/day resulted in gradual reduction in serum TSH. Cranial computed tomography and magnetic resonance imaging revealed a microadenoma of the pituitary gland. Histology of the surgical specimen showed a TSH-producing adenoma with TSH cell cluster islets and decreased numbers of TSH cells in the nonneoplastic pituitary. Cultured cells from the adenoma secreted TSH spontaneously and in response to TRH. This TRH-stimulated TSH secretion was suppressed by T3 in a dose-dependent manner. One year postoperatively, neither residual tumor nor recurrence were seen by computed tomography and magnetic resonance imaging. However TSH, as well as free T3 or T4, was still high and overresponsive to TRH.

Thyrotropin-producing microadenoma associated with pituitary resistance to thyroid hormone.

Cu/dielectric hybrid bonding at low temperatures of no more than 200◦C remains challenging because of the different features of CuCu and dielectric-dielectric (such as SiO2-SiO2) bonding. This paper reports a combined surface activated bonding (SAB) technique for low-temperature Cu-Cu, SiO2-SiO2, and SiO2-SiNx bonding. This technique involves a combination of surface irradiation using a Si-containing Ar beam and prebonding attach-detach process prior to bonding in vacuum. Wafer bonding experiments were conducted at either room temperature or 200◦C. Results of bonding strength measurements, transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS) observations, and X-ray photoelectron spectroscopy (XPS) analysis were reported and discussed to understand the present combined SAB technique. © 2016 The Electrochemical Society. [DOI: 10.1149/2.0201607jss] All rights reserved.

https://iopscience.iop.org/article/10.1149/2.0201607jss/pdf

Combined Surface Activated Bonding Technique for Low-Temperature Cu/Dielectric Hybrid Bonding

A robot-controlled wafer bonding machine was developed for the bonding of different sizes of wafers ranging up to 8 inches diameter. The features of this equipment are such that: (1) After the automatic parallel adjustment for 8-inch wafers to a margin of error within /spl plusmn/1 /spl mu/m, the X, Y, and /spl theta/ axis alignments are performed, allowing a margin of error within /spl plusmn/0.5 /spl mu/m in bonding accuracy; and (2) Room-temperature bonding is enabled using the surface activated (SAB) bonding concept. 8-inch diameter silicon wafers ware successfully bonded by the SAB process at room temperature for the first time. Preliminary investigations across the interface using an Infrared camera show that no bubbles are visibly present in the bonding region.

A new wafer-bonder of ultra-high precision using surface activated bonding (SAB) concept

Effects of aminoguanidine on serum advanced glycation endproducts, urinary albilmin excretion, mesangial expansion, and glomerular basement membrane thickening in Otsuka Long-Evans Tokushima fatty rats

Akira Yamauchi

Papers

Surface activated bonding for new flip chip and bumpless interconnect systems

Thyrotropin-producing microadenoma associated with pituitary resistance to thyroid hormone.

Combined Surface Activated Bonding Technique for Low-Temperature Cu/Dielectric Hybrid Bonding

A new wafer-bonder of ultra-high precision using surface activated bonding (SAB) concept

Effects of aminoguanidine on serum advanced glycation endproducts, urinary albilmin excretion, mesangial expansion, and glomerular basement membrane thickening in Otsuka Long-Evans Tokushima fatty rats