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Excited state dynamics of three iron(II) carbene complexes that serve as prototype Earth-abundant photosensitizers were investigated by ultrafast optical spectroscopy. Significant differences in the dynamics between the investigated complexes down to femtosecond time scales are used to characterize fundamental differences in the depopulation of triplet metal-to-ligand charge-transfer ( 3 MLCT) excited states in the presence of energetically accessible triplet metal-centered ( 3 MC) states. Novel insights into the full deactivation cascades of the investigated complexes include evidence of the need to revise the deactivation model for a prominent iron carbene prototype complex, a refined understanding of complex 3 MC dynamics, and a quantitative discrimination between activated and barrierless deactivation steps along the 3 MLCT → 3 MC → 1 GS path. Overall, the study provides an improved understanding of photophysical limitations and opportunities for the use of iron(II)-based photosensitizers in photochemical applications.

A new class of palladium complexes bearing bidentate 2-hydroxypyridine based ligands have been prepared and fully characterized. The applications of these new complexes towards ketone alkylation reactions with alcohols through a metal-ligand cooperative borrowing-hydrogen (BH) process were demonstrated., (© 2023 The Authors. Published by Wiley-VCH GmbH.)

From the reaction of 2-hydroxy-6-methylpyridine (L) with iron(II) tetrafluoroborate, a new mononuclear iron(III) octahedral complex [FeL 6 ](BF 4 ) 3 has been isolated. The color of the complex reversibly changed from red at room temperature to yellow-orange at the liquid nitrogen temperature. Magnetization measurements indicate that iron(III) in [FeL 6 ](BF 4 ) 3 is in a high-spin state S = 5/2, from room temperature to 1.8 K. The high-spin ground state of iron(III) is also confirmed by DFT calculations. Although the spin-crossover of the complex is not observed, X-band and multifrequency high-field/high-frequency electron spin resonance (ESR) spectroscopy shows rather uncommon iron(III) spectra at room temperature and an unusual change with cooling. Spectral simulations reveal that the S = 5/2 ground state multiplet of the complex can be characterized by the temperature independent axial zero-field splitting parameter of | D | = +2 GHz (0.067 cm -1 ) while the value of the rhombic parameter E of the order of some tenths MHz increases on lowering the temperature. Single crystal X-ray diffraction (SCXRD) shows that the iron(III) coordination geometry does not change with temperature while supramolecular interactions are temperature dependent, influencing the iron(III) rhombicity. Additionally, the DFT calculations show temperature variation of the HOMO-LUMO gap, in agreement with the changes of color and ESR-spectra of the iron(III) complex with temperature.

A modular aerobic oxidation of amines to imines has been achieved using an ortho-naphthoquinone (o-NQ) catalyst. The cooperative catalyst system of o-NQ and Cu(OAc) 2 enabled the formation of homocoupled imines from benzylamines, while the presence of TFA helped the formation of cross-coupled imines in excellent yields. The current mild aerobic oxidation protocol could also be applied to the oxidation of secondary amines to imines or ketimines with the help of cocatalyst, Ag 2 CO 3 , with excellent yields.

A simple procedure for the synthesis of 2-aroylindole derivatives comprising a one-pot CuI-catalyzed SNAr reaction of o-bromochalcones with sodium azide and subsequent intramolecular cyclization through nitrene C-H insertion has been developed. This protocol is also applicable with the 2'-bromocinnamates giving the indole-2-carboxylates.

ortho-Bromophenyl sec-alkyl/sec-alkenyl ketones, on reaction with sodium azide in the presence of copper salts, undergo sequential SNAr followed by Smalley cyclization to provide pseudo-indoxyl derivatives. Some of these pseudo-indoxyl derivatives exhibit interesting fluorescent properties and broad Stokes shifts.

Elderly diabetic patients were followed up prospectively for 4 years to see the effects of blood pressure and dyslipidemia on the development of diabetic micro- and macroangiopathies. We studied 84 elderly diabetic patients whom we divided into four groups according to the association of above complications: (1) diabetes alone group (DM), (2) hypertensive diabetic group (DM + HT), (3) hyperlipidemic diabetic group (DM + HL), and (4) hypertensive and hyperlipidemic diabetic group (DM + HTL). The treatment of diabetes was different among the groups. Glycemic control such as fasting blood glucose and HbA1c did not change between groups or through the follow-up years. As a matter of course, blood pressure of DM was lower and triglyceride of HTL was higher than in other groups. Microangiopathies such as retinopathy, nephropathy, and neuropathy and macroangiopathies such as ischemic heart disease (IHD), cerebral vascular disease (CVD), and arteriosclerosis obliterans were evaluated by using a grading scale according to the severity. The grade of microangiopathies in DM + HT increased gradually during the follow-up years and the grade of IHD and CVD in DM + HTL was relatively higher than in the other groups. Our findings support the general principle of control of hypertension and hyperlipidemia for the prevention of diabetic microangiopathy and macroangiopathy in the elderly diabetic patients.

To elucidate the mechanism of impaired pancreatic A cell function in hypoglycemia in diabetics, the effect of long-term strict glycemic regulations on hypoglycemia-induced glucagon secretion was studied. Firstly, the effect of plasma insulin concentrations on suppressing A cell was studied in healthy volunteers by injecting insulin at doses of 0.1 U/kg and 0.3 U/kg. With 0.3 U/kg of insulin, the rate of fall in glycemia and the nadir of blood glucose were made similar to those with 0.1 U/kg of insulin by glucose infusion with artificial endocrine pancreas. Plasma glucagon response after 0.3 U/kg of insulin was significantly suppressed as compared to that after 0.1 U/kg of insulin, demonstrating that not only hypoglycemic stimulus but also plasma insulin concentration were important determinants responsible for glucagon secretion in insulin-induced hypoglycemia. Secondly, effect of strict glycemic control was studied. Short-acting insulin at a dose of 0.1 U/kg was injected in an intravenous bolus form into 12 insulin-dependent (IDDM) and 9 non-insulin-dependent (NIDDM) diabetics before and 1-3 months after strict glycemic control with multiple insulin injections therapy. Before strict glycemic regulations in IDDM, no significant rise in plasma glucagon concentrations was observed during the insulin-induced hypoglycemia. In NIDDM, a rise in plasma glucagon concentrations was observed, though the response was delayed. After strict glycemic regulations, in patients with residual endogenous insulin secretion, the glucagon response to hypoglycemia improved considerably in IDDM and normalized in NIDDM. In IDDM and NIDDM, improvement in glucagon response to hypoglycemia related positively to daily urinary secretion rate of C-peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal and metabolic characteristics of diabetes mellitus in the elderly were investigated in the following groups; elderly DM subdivided into obese DM and non-obese DM, elderly non-DM subdivided into obese and non-DM and non-obese non-DM, adult DM and adult non-DM. Responses of plasma glucose, insulin and glucagon during oral glucose tolerance test (OGTT), arginine tolerance test (ATT) and intravenous glucose tolerance test (IVGTT) were measured individually and the daily urinary C-peptide excretion (U-CRP), fasting plasma levels of free fatty acid (FFA), triglyceride (TD), total cholesterol (TC) and HDL-cholesterol (HDL-C) were also measured. In comparison with adults, insulin responses in IVGTT and ATT in elderly non-DM were low but not in OGTT. It was noteworthy that glucagon response during OGTT in elderly DM was considerably lower than adult DM, probably due to factors other than insulin deficiency. Comparing elderly DM and elderly non-DM, the initial response of insulin in OGTT was found to be low in elderly DM but not in total response. In the comparison between the obese and the non-obese, higher insulin levels in elderly obese DM than in elderly non-obese DM during OGTT, IVGTT and ATT were observed, implying decreased insulin sensitivity. This difference, however, was not apparent between elderly obese non-DM and non-obese non-DM. A good correlation between U-CPR and the response of plasma insulin in OGTT was shown even in the elderly but not between U-CPR and that of plasma insulin in IVGTT.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: The relationships between age and diastolic left ventricular function, and age and mitral valve motion were studied., Design: The maximum velocity of circumferential fibre lengthening (negative peak Vcf) of left ventricular function and mitral valve motions, such as mitral valve E and A wave amplitude, D-E and E-F slopes, and their relationships were assessed., Subjects: Twenty young, healthy persons (10 males and 10 females) from 20 to 47 years old (mean 34.5), and 26 older healthy subjects (five males and 21 females) from 62 to 94 years old (mean 80.0) were studied., Intervention: M-mode echocardiography of left ventricular function and mitral valve motion were recorded and digitized for the assessment., Main Results: Age showed a significant (P = 0.0001) correlation with negative peak Vcf (r = -0.62), with E wave amplitude (r = -0.83), with D-E slope (r = -0.71) and with E-F slope (r = -0.83). Negative peak Vcf was correlated with E wave amplitude (r = 0.51, P = 0.0007), with D-E slope (r = 0.31, P = 0.058), with E-F slope (r = 0.53, P = 0.0005). Its relations with mitral valve A wave amplitude was r = -0.30, P = 0.17 in the elderly group and r = 0.003, P = 0.99 in the younger group. A significant (P < 0.001) positive, linear correlation was observed between age and mitral A/E ratio (r = 0.82)., Conclusions: The easily measurable mitral valve E-F slope and E wave amplitude can be used to assess early diastolic left ventricular function in ageing. Left atrial contraction appears to play a more important role in the elderly, compensating for the decline in early diastolic left ventricular function.

To assess the interrelationship between the cardiac and cerebral circulations, simultaneous measurements of cardiac output (CO) and common carotid blood flow volume (CCBFV) was performed by M-mode echocardiography of the left ventricle, and quantitative ultrasonic Doppler blood flowmetry of the common carotid artery. The subjects studied were 12 healthy persons living in a home for the elderly ranging in age from 62 to 99 years. These subjects were divided into two groups: those who were in their 90s (Group I, 5 females) with a mean age of 93.6 +/- 3.5 years (mean +/- SD), and those who were in their 60s to 80s (Group II, 1 male and 6 females) with a mean age of 77.1 +/- 8.1 years. The average CO in Group I was 2.85 +/- 0.37 L/min, and 4.18 +/- 0.52 L/min in Group II. The average CCBFV was 4.74 +/- 0.64 dl/min in Group I, and 4.44 +/- 1.01 dl/min in Group II. The ratio of CCBFV to CO was 16.6 +/- 1.32% in Group I, and 10.6 +/- 1.45% in group II. Good linear correlations of y = 1.44x +0.65 (r = 0.82) in Group I and y = 1.58x - 2.15 (r = 0.81, p less than 0.05) in Group II were observed between CO (x) and CCBFV (y). No such close correlations were observed between CCBFV and other indices of left ventricular function such as circumferential fiber shortening or fractional shortening of the diameter of the left ventricle (r less than or equal to 0.56, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Rabbits maintained on a persistent high sugar diet eventually develop diabetes mellitus with a marked decline in glucose tolerance, but no studies have been conducted on the associated bone changes in these high sugar diet-induced diabetic rabbits (HSDD-R). Radiographs have revealed a significant thinning of the femoral cortex of these rabbits with markedly decreased bone mass. Scanning electron microscopy of the femoral cortex using the freeze-fractured technique have revealed the loss of a typical structure of Haversian canals and the surrounding concentric and radiating lamellar bones and also the loss of fibrous components in the section. The border created by the cement line was indistinct and resulted in amorphous changes. Formation of heterogenous bundles of fibrous components different from the usual reticular structure was seen within the subendothelial space of the Haversian canals. These results indicate that qualitative changes can apparently occur in the bone along with the development of osteopenia in the diabetic state.

The effects of aging on the diastolic and systolic functions of the left ventricle were studied by echocardiography as follows. (1). Maximum velocity of circumferential fiber lengthening (negative peak Vcf) and shortening (peak Vcf) was assessed by digital M-mode echocardiography in 20 healthy young subjects and 26 healthy elderly subjects. The mean value of negative peak Vcf (-cir/sec) was -3.87 +/- 0.85 in the 20's. -4.48 +/- 1.14 in the 30's, -3.71 +/- 1.21 in the 40's, -2.70 +/- 0.90 in the 60's, -2.57 +/- 0.64 in the 70's, -2.33 +/- 0.77 in the 80's and -2.57 +/- 0.65 in the 90's showing significant difference among young and elderly groups (p less than 0.05- p less than 0.005). The mean value of peak Vcf showed no significant difference among young and elderly groups except for the group in the 30's which showed significant (p less than 0.05) difference between other groups. (2). Indices of the left ventricular systolic and diastolic functions were calculated by standard M-mode echocardiographic technique in 227 healthy subjects from 5 to 94 years in age by dividing them into 3 young groups and 4 elderly groups. As for the left ventricular internal diameters a tendency of increase was observed in the end diastolic diameter of the left ventricle in accordance with ageing. Fractional shortening of the left ventricular diameter which ranged from 36.2% to 36.7% in the 3 young groups and 36.9 to 40.3% in the 4 elderly groups and cardiac output showed no age dependent decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

The prevalence and degree of mitral annular calcification (MAC) in elderly cases of hypertrophic cardiomyopathy with asymmetric septal hypertrophy (ASHCM) were studied in comparison with healthy elderly and chronic hypertensive elderly with concentric left ventricular hypertrophy (HT + LVH) by echocardiography. In seven elderly patients with ASHCM (mean age 77.3 +/- 8.1 years) severe MAC was observed in all cases (1 male and 6 females) and systolic anterior motion of the mitral valve (SAM) was present in 3 cases, incomplete in 2 and absent in 2 cases. Of 57 healthy elderly with a mean age of 78.8 +/- 8.8 years, 8 subjects (1 male and 7 females, 14%) showed MAC. The prevalence of MAC was 0% in the sixties, 14% in the seventies, 16% in the eighties and 29% in the nineties. MAC was severe in four subjects above eighty years old. In 3 cases with HT + LVH with a mean age of 72.3 +/- 4.7 years no MAC was observed and SAM was present in one, partially observed in one and absent in one case, respectively. Serum calcium (Ca) and phosphorus (P), reported to be related with the formation of MAC, and fasting blood sugar level (FBS) were evaluated. In healthy elderly with MAC, serum Ca was 8.78 +/- 0.46 mg/dl, P 3.55 +/- 0.37 mg/dl and FBS 97.75 +/- 29.01 mg/dl, P 3.55 +/- 0.37 mg/dl and FBS 97.75 +/- 29.01 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

For the application of the glycemic index (GI) to the therapy of diabetes mellitus (DM) in the elderly, effects of aging and foods were studied in 3 groups of subjects, conducting 3 oral tests of equal calories, namely, glucose, white bread (high-GI meal) and kidney beans (low-GI meal). Group I: healthy adults (N = 7), Group II: elderly non-DM (N = 7), Group III: elderly DM (N = 7). No significant changes with age could be found in blood glucose or GI. However, ingestion of a low-GI meal revealed excellent inhibitory effects upon postprandial glycemic elevation in the elderly diabetics. This implies the clinical usefulness of a low-GI meal (beans) for postprandial glycemic regulation in elderly diabetes mellitus.

A new insulin delivery device has been developed and tested. It includes a reservoir, a pump, and a power pack. The reservoir holds 75 ml and is coupled to a precision peristaltic pump whose delivery can be set to any one of 128 different flow rates from 0 to 80 microliter/min (+/- 1.6% over 10 months) using the flow rate controller included in the battery power pack. The system weighs 525 g, consuming 50 mW at the maximum pumping rate, proportionately less at lower rates. Ten pumps have undergone bench tests for 30 days. One has been subjected to an extended life test of 16 months without change of tubing while seven complete systems have been used on dogs to demonstrate their capability for precise long-term (up to 16 months) intravenous insulin therapy. With this system, experimental diabetes has been controlled in 7 dogs for periods now extending beyond 16 months. This device now qualifies for-long term studies on hospitalized patients with diabetes mellitus.

For closed-loop glycemic control on IDDM, closed-loop sc insulin infusion algorithm has developed by analysing the pharmacokinetics of sc insulin absorption. With the algorithm, daily glycemic excursion in IDDMs was controlled to near-normal levels. These data suggested that the closed-loop sc insulin infusion algorithm might be feasible to regulate glycemia in diabetic patients for a long-term period by wearable artificial endocrine pancreas.

Water-in-oil-in-water (W/O/W) insulin micelles were prepared, and the possibility of insulin absorption in a micellar form was examined. In this preparation, insulin was trapped in oil droplets of oleic acid in glyceryl-alpha-monooleate. (1) W/O/W insulin micelles were absorbed from the ligated jejunal loop of rabbits to the order of 12.3 to 58.5% of the dose given (10 mU/kg body weight) during the 3-h experimental period. (2) Alloxan diabetic rats were treated with intrajejunal administration of W/O/W insulin micelles at a dosage of either 25 or 50 mU/100 g body weight, three times daily for as long as 14 days. During treatment, a significant reduction in the daily excretion of urinary glucose was observed, concomitant with a decrease in fasting blood glucose. Quantitative estimates suggested that the effectiveness of 25 mU/100 g of intrajejunal W/O/W insulin micelles was comparable to that of regular insulin at a dosage of 1 mU/100 g i.m. These results would indicate that W/O/W insulin micelles, when given enterally, are more effective in lowering blood and urinary glucose levels than W/O/W insulin emulsions in which insulin was trapped in oil droplets of triglyceride.

For the long-term clinical use of the wearable artificial endocrine pancreas, a fail-safe system is an essential mechanism. Several hardware alarm systems have been incorporated for battery-down, and short-run of the pumps. Software alarm systems for overflow or underflow of the AD converter, empty bags, hypoglycemia, hyperglycemia, abnormal values of parameters, and excessive insulin infusion have also been built into the system. The software noise filter was effective in eliminating superimposed artificial noises and the noises induced by muscle exercise. Sudden changes in sensor output during glycemic control of diabetics due to short circuit, or disconnection of the sensor lead, were detected as overflow or underflow of the AD converter. A gradual change in the sensor output was heralded by the hyper- or hypoglycemia alarm sound. These data indicated that the fail-safe system built into the wearable artificial endocrine pancreas is useful for the long-term glycemic control of diabetics.

Duodenal ulcer beyond the bulb occurred in a diabetic patient when he was in ketoacidotic coma causing serious anemia. Early investigation of the stomach and duodenum by endoscope was quite valuable for evaluating this bleeding complication and the healing process of the lesion was serially recorded. Since several cases of diabetic coma have been reported to die from gastrointestinal bleeding, this report presents the important aspect in the management of diabetic coma, and usefulness of emergency endoscope.

A needle-type glucose sensor has been developed using a platinum electrode covered with immobilized glucose oxidase. Experiments with albumin-saline solution in vitro showed that at 5.5 mmol/l glucose concentration the output current generated was 1.2 +/- 0.4 nA (mean +/- SD). The current increased as a linear function of glucose concentration over the range (0-27.7 mmol/l). The response time to reach 90% of the final plateau value was 16.2 +/- 6.2s. The signal-to-noise ratio of the sensor was 15.8 +/- 2.6 decibels. The temperature coefficient in output was 2.3 +/- 1.0%/degrees C. The current output was not affected significantly by changes in oxygen tension of the solution in the range 25-150 mmHg. In vivo, the output current of sensors inserted into the subcutaneous tissues of dogs was directly related to blood glucose concentrations after oral glucose or meals. Daily checking of the sensors maintained in subcutaneous tissues in five dogs showed that the sensitivity decreased gradually to 87.2 +/- 7.6% at 72 h, and dropped significantly to 57.4 +/- 7.0% of the initial output by 96 h. A wearable artificial endocrine pancreas (18.0 x 17.7 x 7.9 cm, 700 g) was developed, consisting of a needle-type glucose sensor, a microcomputer system and a pump driving mechanism. Three pancreatectomized dogs were fitted with the system by inserting the sensor into subcutaneous tissue. By renewing the sensor every fourth day, the device could maintain the daily glucose variations in diabetic dogs within the range 5-9.5 mmol/l for 7 days.

A validation of small-dose insulin infusion therapy was studied by the constant i.v. infusion of various doses of insulin into ketoacidotic depancreatized dogs. Constant insulin infusion of 5 x B, 10 X B, 30 X B and 50 X B (B = 225 microunit/kg/min) was performed for 3 h by mechanical pump. The following results were obtained: (1) plasma concentrations of immunoreactive insulin (IRI) increased proportionally to the dose of infused insulin, but the higher IRI did not result in a greater fall in plasma glucose concentration, correspondingly; the mean rate of fall in plasma glucose concentration of 5 x B was not significantly lower than that of 50 x B; beta-hydroxybutyrate and arterial pH improvements were observed in each group during the 3-h insulin infusion. These data suggested that for the improvement of diabetic ketoacidosis, the insulin infusion rate of more than 30 x B, which raised the plasma IRI levels above the physiological range, was not essential; (2) the necessity of potassium supplementation during the small-dose insulin infusion was suggested if the pre-treatment level of serum potassium was low. These results confirmed that in the absence of infection or severe acidosis small-dose insulin infusion therapy is as effective as the conventional large-dose insulin therapy.