Psammomys lapses into fully fledged diabetes when maintained on a high-energy diet. Progression to diabetes has been classified into stage A of normoglycemia and normoinsulinemia (<120 mg/ml and 100 mU/L, respectively); stage B of hyperinsulinemia (100-300 mU/L) with marked insulin resistance in the face of normoglycemia; stage C of pronounced hyperinsulinemia with hyperglycemia < or =500 mg/ml; stage D at 6-10 weeks after stage C, featuring further hyperglycemia and loss of insulin. Insulin resistance expressed in Psammomys at stages B and C was demonstrated by nonsuppression of the hepatic gluconeogenesis enzyme phosphoenolpyruvate carboxykinase by the endogenous hyperinsulinemia and by the reduced capacity of insulin to activate muscle and liver tyrosine kinase of the insulin receptor. Diabetes at stage C, but not at stage D, was fully reversed to stage A by restricting the food ration of animals by half (from 14 to 7 g/day) for 10-14 days. We examined islet beta cells of Psammomys in the four stages of progression to diabetes by staining for insulin as well as for apoptosis by the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and visualizing the biotin-labeled cleavage sites. Psammomys in stage A had insulin-laden beta cells. In stage B, a hypertrophy and partial insulin depletion of beta cells was evident with negative TUNEL staining. In stage C, beta cells were markedly depleted of insulin, and their number within the islets decreased, but the TUNEL staining was virtually negative. In stage D, beta cells were markedly diminished within the islets, almost void of insulin, showing distinct TUNEL staining of beta cells. These results indicate that prolonged exposure of islets to in vivo hyperglycemia with beta-cell overtaxation induces nuclear disintegration with irreversible damage to the insulin-secretion apparatus. This precludes the return to normalcy by restricting the food intake of Psammomys. The appearance of cells with TUNEL-positive staining may serve as a marker of impending irreversibility of nutritionally induced diabetes.

The genetically endowed quality of beta-cells determines their potential to cope with nutritionally enhanced insulinogenesis, Certain species may respond to the inherent hyperphagia with long-lasting compensatory insulin secretion entailing obesity. Other animal species and certain human populations with labile pancreas are unable to maintain the hypersecretion of insulin in response to the imposed nutrient load, thus causing the transition from type 2 to type 1 diabetes. Insulin resistance is most probably an inherited trait proximal to the insulin receptor responsible for the cellular signaling defect that leads to the development of type 2 diabetes with the possibility of consequent beta-cell failure in both animals and humans, The fact that obese Individuals often do not progress to full-fledged diabetes indicates that they may be endowed with particularly resilient beta-cells. The lasting hyperinsulinemia promotes the conversion of glucose to fat and restrains fat release from adipose tissue, protecting beta-cells from gluco- or lipotoxic lesion, similar to the obese animal species mentioned here. The impaired glucose tolerance and hyperglycemia should not be considered as markers of beta-cell function, but as an incitement of oversecretion culminating in apoptosis, Apoptosis is a pathophysiologic process distinct front, and preceding, necrosis, Insulin resistance can be reversed and apoptosis prevented by reducing the nutritionally induced hyperglycemia in time. Psammomys obesus illustrates this course of events and is an excellent model of human transition from type 2 to type 1 diabetes, demonstrating the reversibility of the process and manifesting beta-cell nuclear fragmentation, which causes a failure of biosynthetic capacity in the final stage of nutritionally induced diabetes.

Hyperproinsulinemia is a characteristic feature of non-insulin-dependent diabetes mellitus (NIDDM) caused by pancreatic beta-cell dysfunction through a secretion-related alteration or impaired proinsulin processing. We have investigated the insulin processing and secretion in Psammomys obesus fed with low- and high-energy diets, which represent a model for diet-induced NIDDM. With a high-energy diet the animals develop hyperglycemia and hyperinsulinemia, whereas those maintained on a low-energy diet remain normoglycemic. Although a large amount of insulin immunoreactivity was detected in beta-cells of the normoglycemic compared to hyperglycemic animals, in situ hybridization for insulin mRNA demonstrated a particularly high signal in the beta-cells of the hyperglycemic animals. By electron microscopy, the beta-cells of normoglycemic animals displayed large accumulations of secretory granules, whereas those of the hyperglycemic animals contained very few granules and large deposits of glycogen. These results reflect a secretory resting condition for the cells of the normoglycemic animals in contrast to stimulated synthetic and secretory activities in the cells of the hyperglycemic ones. Using colloidal gold immunocytochemistry at the electron microscopic level, we have examined subcellular proinsulin processing in relation to the convertases PC1 and PC2. Immunolabeling of proinsulin, insulin, C-peptide, PC1, and PC2 in different cell compartments involved in beta-cell secretion were evaluated. Both PC1 and PC2 antigenic sites were detected in beta-cells of hyperglycemic Psammomys, but their labeling intensity was weak compared to the cells of normoglycemic animals. In both groups of animals, higher levels of PC2 were found in the Golgi apparatus than in the immature granules. Major decreases in proinsulin, insulin, PC1, and PC2 immunoreactivity were recorded in beta-cells of the hyperglycemic Psammomys. In addition, all these antigenic sites were detected in lysosome-like structures, revealing a major degradation process. These results suggest that the insulin-secreting cells in hyperglycemic Psammomys obesus are in a chronic secretory state during which impaired processing of proinsulin appears to take place.

It has been previously shown that a metabolite of piroxicam but not piroxicam itself causes phototoxicity to cells in vitro after exposure to UVA (320–400 nm) radiation. The phototoxicity mechanism for this metabolite, 2‐methyl‐4‐oxo‐2H‐l,2‐benzothiazine‐l,l‐dioxide (Compound I), was investigated. In vitro phototoxicity to human mononuclear cells was assayed using 0.5 m M Compound I and UVA radiation. The UVA fluence required for phototoxicity of Compound I was lower by a factor of 2‐3 in D 2 O buffer compared to H 2 O buffer. Superoxide dismutase and mannitol, which remove O 2 ‐ and OH”, respectively, do not decrease the phototoxicity. The photodecomposition of Compound I was inhibited by sodium azide, enhanced by human serum albumin and unaffected by mannitol. Stable photoproducts of Compound I were not toxic to the cells. The quantum yield of singlet oxygen based on its emission at 1270 nm was 0.19 and 0.35 for Compound I and s2 ± 10 ‐3 and 10 ‐2 for piroxicam in D 2 O and C 6 H 6 , respectively. While the extremely low quantum yield for singlet oxygen from piroxicam appears to account for its lack of phototoxicity, the phototoxicity mechanism for its metabolite, Compound I, most likely does involve singlet oxygen.

Some properties of the first triplet and singlet excited states of 4'-aminomethyl-4,5',8-trimethylpsoralen have been determined by laser flash photolysis and spectrofluorimetry. In water the lowest triplet has an intrinsic lifetime of 100 microseconds and is quenched by the molecule in its ground state with a rate constant kQ = 10(9) M-1 . s-1 and by thymine with a rate cconstant kq = 2 . 10(8) M-1 . x-1. Addition of 0.5 mg/ml of calf thymus DNA causes the disappearance of the aminomethylpsoralen triplet absorption immediately after the laser flash excitation and extinguishes the fluorescence emission of a 6 . 10(-5) M solution of aminomethylpsoralen. These experiments show that the first singlet excited state which is rapidly deactivated in the presence of DNA could be the precursor of the first pyrimidine photoadduct.

— The triplet absorption spectra, lifetimes, extinction coefficients, eTT, and intersystem crossing quantum yields to the lowest triplet T1, oT1, of thymidine, thymidine monophosphate, uridine and uridine monophosphate, have been determined in various solvents at 300 K. The effect of H-bonding on oT1, of these nucleosides and nucleotides and also of uracil has been determined and discussed. This effect allows, an ordering of l,3n, π* and 1,3π, π* states in protic and aprotic solvents.

Abstract— In the comparative method of determining the triplet quantum yield øT by laser flash absorption spectroscopy, general equations are established (1) for describing the dependence of øT with laser intensity and (2) for absolute actionometry of a laser pulse. Applications to specific examples are discussed.

The reaction of the lowest triplet of duroquinone, 3Q, with tertiary amines (triethylamine TEA, diethylaniline DEA, triphenylamine TPA) has been investigated by laser flash absorption spectroscopy in non-polar (cyclohexane or benzene) and polar (acetonitrile) solvents. Three pathways of 3Q deactivation involving an exciplex as intermediate were observed: (i) an electron transfer to 3Q from TPA and DEA in a polar solvent, (ii) a H atom transfer to 3Q from DEA in a non-polar solvent and from TEA in a non-polar or a polar solvent, (iii) a physical quenching of 3Q by TPA in a non-polar solvent with no photoreduction products.

The extinction coefficients for the triplet–triplet maxima of all-trans-β-carotene, 15,15′-cis-β-carotene, all-trans-lycopene, 7,7′-dihydro-β-carotene, all-trans-retinol, all-trans-retinal, 13-cis-retinal and all-trans-retinylidene-N-butylamine have been determined via pulse-radiolysis using a refinement of the energy transfer technique introduced previously. Together with Wolff and Witt's data, the coefficient found for β-carotene suggests that ∼10 % of the total carotene present in photosynthesising spinach chloroplasts is available as a protective valve against overillumination.These extinction coefficients were employed to estimate, via laser flash photolysis, the corresponding singlet → triplet intersystem crossing quantum yields using 265 and 353 nm excitation. The very low yields ( < 0.001) found for β-carotene and derivatives mean that carotenoid triplets formed in chloroplasts during the course of the valve function could not have been formed directly, but only via triplet–triplet energy transfer sensitation via another triplet (chlorophyllT?), or via1O2 quenching. The low cross-over efficiencies also mean that in their accessory pigment role no carotenoid excited singlets are wasted in crossing over to the triplet state.

Abstract. Nanosecond flash photolysis of rhodopsin with 530 or 353 nm light produces an initial transient absorption spectrum with peaks at ˜57O and ˜420nm, and a subsequent transient species with a maximum absorption at 480 nm. These results are interpreted as the initial formation of prelumi‐rhodopsin (570 nm) followed by its conversion to lumirhodopsin (470 nm). The peak at 420 nm in the first transient may be due to either hypsorhodopsin or isorhodopsin.

The triplet—triplet absorption spectra, quantum efficiencies of intersystem crossing, triplet extinction coefficients, and triplet energy levels of 1,6-diphenyl-1,3,5-hexatriene, and 1,8-diphenyl-1,3,5,7-octatetraene, in ethanol and benzene have been obtained. The quantum efficiencies of intersystems crossing are found to be less than 0.03 for both molecules in both solvents, indicating that the excited singlet is efficiently deactivated by internal conversion and flourescence emission. The triplet—triplet absorption spectra and the triplet energy level of 1,6-diphenyl-1,3,5,hexatriene are compared with previous results in other solvent systems.

Chemischer InformationsdienstVolume 7, Issue 36 Physical Organic Chemistry ChemInform Abstract: LASER FLASH SPECTROSCOPY OF TRIS(2,2′-BIPYRIDINE)RUTHENIUM(II) IN SOLUTION R. BENSASSON, R. BENSASSONSearch for more papers by this authorC. SALET, C. SALETSearch for more papers by this authorV. BALZANI, V. BALZANISearch for more papers by this author R. BENSASSON, R. BENSASSONSearch for more papers by this authorC. SALET, C. SALETSearch for more papers by this authorV. BALZANI, V. BALZANISearch for more papers by this author First published: September 7, 1976 https://doi.org/10.1002/chin.197636034AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume7, Issue36September 7, 1976 RelatedInformation

Laser flash spectroscopy has been used to study the lifetime, extinction coefficient, oscillator strength and quantum yield of formation (ϕT) of duroquinone triplet 3Q in solution. Reaction of this triplet with solvent leads in ethanol and cyclohexane to the neutral semiquinone QH. Reaction of this triplet with itself leads in water to the anion Q·– and in cyclohexane and ethanol to the excited singlet 1Q* followed by 3Q. Transient spectra and kinetic measurements demonstrate that triplet-triplet annihilation is the only path for duroquinone photoreduction in water. ϕT in the solvents used is unity (±0.15), ϕ(QH) is 0.4 (±0.1) in ethanol and 0.09 (±0.03) in cyclohexane.Laser flash spectroscopy of the duroquinone + durohydroquinone system gave rise to spectra of the transient species 3Q and QH linked by isobestic points in ethanol and cyclohexane. In water 3Q and Q·– were observed, again linked by isobestic points. The observed reaction 3Q + QH2→ 2 QH allowed a determination of the QH extinction in ethanol and cyclohexane. The formation of a triplet exciplex 3(Q, QH2) is suggested.

Chemischer InformationsdienstVolume 7, Issue 22 Preparative Organic Chemistry ChemInform Abstract: DUROQUINONE TRIPLET REDUCTION, IN CYCLOHEXANE, ETHANOL AND WATER, AND BY DUROHYDROQUINONE E. AMOUYAL, E. AMOUYALSearch for more papers by this authorR. BENSASSON, R. BENSASSONSearch for more papers by this author E. AMOUYAL, E. AMOUYALSearch for more papers by this authorR. BENSASSON, R. BENSASSONSearch for more papers by this author First published: June 1, 1976 https://doi.org/10.1002/chin.197622121AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume7, Issue22June 1, 1976 RelatedInformation

Abstract— Absorptions of the triplet excited states of five carotenoids (15,15'‐ds phytoene, all‐trans phytoene, C‐carotene, spheroidene and spirilloxanthin), extracted from the photosynthetic bacteria Rhodopseudomonas spheroides and Rhodospirillum rubrum, have been detected in solution using pulse radiolysis and laser flash photolysis. Triplet lifetimes, extinction coefficients, lowest energy levels and quantum efficiencies of formation have been determined. Comparison of the carotenoid triplet energy levels with that of O2('Δg) suggests that spirilloxanthin, spheroidene and possibly alsoζ‐carotene, would be expected to protect against photodynamic action caused by O2 ('Δg), but not cis or trans phytoene. The S→T intersystem crossing efficiences of all five polyenes were found to be low, being a few per cent or less. In their protective role these triplet states can only therefore be effectively reached via energy transfer from another triplet, except in the case of O2 ('Δg). The low crossover efficiencies also mean that light absorbed by such carotenoids in their possible role as accessory pigments would not be wasted in crossing over to the triplet state.

THIS note presents results from a neodymium laser flash spectroscopy study of bovine rod outer segments (ROS), the only chromophore of which is rhodopsin. Previously unreported transients are interpreted in terms of a charge-transfer excited state which gives rise to radicals and/or triplets.

Abstract— Thymine and uracil triplet‐triplet absorption spectra and triplet excited state lifetimes have been observed in acetonitrile and water by nanosecond laser flash spectroscopy. A study of triplet energy transfer from these pyrimidines to retino! has also allowed an estimation of the triplet extinction coefficient εTT of thymine and uracil. These εTT were then used to determine the triplet quantum yields ØT of both pyrimidines in acetonitrile and water.