Resonant-grating reflection extended to wide-band, large-aperture beams by waveguide-mode coalescence.

The resonant reflection of a free-space beam from a slab waveguide grating is rendered high bandwidth and angularly robust by using a bimodal high index waveguide. A deep double-sided corrugation gives rise to the coalescence of the resonant reflection peaks resulting in a top-hat reflection spectrum. A low-cost waveguide technology based on solar cell amorphous silicon is demonstrated in the near infrared in a polarizer application.

[Renal manifestations of Kimura disease. Apropos of a case]. / Manifestations rénales de la maladie de Kimura. A propos d'un cas.

A nephrotic syndrome with focal sclerosis associated with Kimura's disease is reported in a young asiatic man. The nephrotic syndrome started three years prior to the usual skin tumors and lymph nodes involvement. Epidemiological, clinical and nosological characteristics of Kimura's disease are discussed. Renal manifestations are the only visceral localisations of the disease. Thirteen Kimura's disease associated with documented nephrotic syndromes have been reported in german-english literature. They display a wide variety of histologic patterns. Their clinical course do not differ from the primary form of nephrotic syndrome with identical histology.

General pharmacology of S 15261, a new concept for treatment of diabetes.

The new compound S 15261 (CAS 159978-02-6) is the I-isomer of 3-[2-[2-[4-[2-(alpha-Fluorenylacetylamino)ethyl]benzoyloxy]ethylam ino]-1- methoxyethyl]trifluoromethylbenzene. The general synthetic pathway used for the preparation of S 15261 and related esters is given in this paper. This compound was selected for its promising therapeutical action on blood glucose, insulin resistance and associated risk factors present in patients with non-insulin-dependent Diabetes mellitus (NIDDM). The general pharmacological profile of S 15261 was investigated. The data given in this paper show that S 15261 has presented a very low acute toxicity (lethal dose in mice greater than 1600 mg/kg orally) and did not induce significant behavioural changes in rats. A poor anorectic effects was observed after acute administration in rats. In guinea pigs S 15261 acutely induced a significant and dose-dependent hypoglycaemic effect (ED25 = 40 mg/kg orally). Biogenic amines and their metabolites in different structures of the brain were only slightly affected after acute administration of S 15261. Chronic administration of this compound (2.5 mg/kg bid for 14 days p.o.) did not cause significant alterations in the brain amines content, with the exception of an increase of serotonin (19%) in the striatum, a result not confirmed by the dose-effect study (from 1 mg/kg to 12.5 mg/kg bid for 14 days p.o.). In vitro binding assays with 31 different receptors did not show significant affinity of S 15261 for any of them. The rat arterial blood pressure was decreased (12 mmHg) after acute (25 mg/kg i.v.) or repeated administration (2.5 mg/kg bid for 14 days p.o.) without any dose-dependent effect. We therefore conclude that S 15261 may not have significant adverse effect even at doses higher than the pharmacological effective range of doses. Although the mechanism of action of this new class of compounds was not fully understood, other pharmacological data suggest that S 15261 acts at both the liver (intraportal infusion) and skeletal muscle (microdialysis studies) at least in part to enhance insulin sensitivity. For all these activities S 15261 may be useful to treat patients with NIDDM or insulin resistance known to be the major risk for onset of NIDDM.

S15261 antagonises amylin-induced impaired glucose tolerance.

Amylin has been postulated to antagonise or inhibit the action of insulin in peripheral rat tissues and thus contribute to, or be responsible for, the development of insulin resistance. We have recently reported that S15261 is a compound capable of increasing insulin sensitivity in ageing insulin resistant rats. In order to assess whether S15261 had any effects on amylin induced insulin resistance we used a model where amylin causes an impairement in glucose tolerance in an acute manner, by means of an intraportal infusion of the hormone in normal rats. We report here that S15261 can antagonise this amylin-induced impaired glucose tolerance.

S15261, a new compound for the treatment of the insulin resistance syndrome.

A new oral agent, S15261 (the L-isomer of 3-[2-[2-[4-[2-[alpha-fluorenyl acetyl amino ethyl] benzoyloxy] ethyl amino] 1-methoxy ethyl] trifluoromethyl-benzene), has been developed for the treatment of the so-called "insulin resistance syndrome". In obese, insulin-resistant ageing Sprague-Dawley rats, chronic treatment with S15261 (0.5-2.5 mg.kg-1.day-1 twice per day, for 14 days) resulted in dose-dependent decreases in plasma insulin (43%), and triglyceride levels (36%), and in an increase of the glucose disposal rate during an intravenous glucose tolerance test (IVGTT) (48.5%). An increase in peripheral insulin sensitivity produced by S15261 was revealed by the glucose clamp technique. Thus, the glucose infusion rate was increased by 20% whilst steady-state insulin levels decreased by 15%. At the higher doses S15261 led to a decrease in body weight (3%), plasma glucose (13%) and blood pressure (8 mm Hg) in mildly hypertensive animals. At the doses used to achieve these results, the compound has no hypoglycaemic activity in normoglycaemic animals. Acute administration of S15261 directly into the portal vein provoked a marked increase in glucose disappearance rate during an intravenous glucose tolerance test (60%) and also in the pancreatic response to the glucose challenge. Thus, acute administration of the compound has a direct effect on glucose metabolism. These data suggest that S15261 could be a useful agent for the treatment of the insulin resistance syndrome.

8-OH-DPAT induces a selective increase in protein intake in ageing overweight animals.

We have examined the effects of a 5-HT1A receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) on food preference in ageing rats that had been given a 'palatable' meal 15 min before administration of the drug. Ageing rats consumed a greater amount of the 'palatable' pre-meal than the young rats. In young rats lipids were the predominant source of calories, but in old animals lipid and protein consumption was similar. Administration of 8-OH-DPAT resulted in an increase in total caloric intake in both groups. Concomitant with this there was a significant increase in protein intake in both groups, which was most important in ageing rats, where proteins became the predominant source of calories.

Effect of activation of the serotoninergic system during prolonged starvation on subsequent caloric intake and macronutrient selection in the Zucker rat.

Starvation or dietary restriction are known to modify post-fasting dietary self-selection. We have examined the effects of activation of the serotoninergic system and food deprivation on macronutrient self-selection following a period of starvation. Rats were starved for 4 days and either treated or not with dl-fenfluramine or fluoxetine. Starved untreated animals showed a post-fasting anorexia and an increased preference for carbohydrate intake, even though lipids remained the preferred source of calories. Treatment with fenfluramine or fluoxetine increased post-fasting anorexia, abolished the preference for carbohydrates and decreased lipid intake. Fluoxetine, but not fenfluramine, resulted in decreased protein intake as well. Following a 2-day refeeding period ad libitum, during which the animals were not treated with drugs, the anorectic effect of fenfluramine disappeared but that of fluoxetine remained unchanged. In addition, we noted that at an equimolar dose to dl-fenfluramine (100 mumol/kg/day) fluoxetine treatment resulted in the death of all the animals in the group by the second day of refeeding; no deaths were observed in any of the other groups. In conclusion, we confirm a post-starvation anorexia and increased carbohydrate intake following long-term fasting. In addition we show that activation of the serotoninergic system abolishes the increase in carbohydrate intake and potentiates post-starving anorexia.

Improvement in glucose tolerance of insulin resistant rats after chronic or acute administration of benfluorex.

The effects of Benfluorex administration on glucose tolerance have been examined in young and old Sprague Dawley rats. The ageing rats were used as a model of insulin resistance. Chronic oral administration of Benfluorex decreased triglycerides levels and normalized glucose tolerance in ageing rats, independently of effects on body weight. Acute intraportal administration of 0.45 mg/kg/h of Benfluorex for 30 min resulted in a 50% increase in glucose tolerance in old rats, but did not modify that in young rats. The improved glucose tolerance brought about by Benfluorex in an animal model of insulin resistance may suggest a wider therapeutic application in man, to include insulin resistant states as type II diabetes or Syndrome X.

Adsorption of bovine serum albumin onto glassy carbon in a Couette flow. Effect of shear rate on the adsorption kinetics and on the structure of the adsorbed proteic layer.

Adsorption of bovine serum albumin onto glassy carbon is investigated by analysing the time-variation of the double-layer capacitance recorded during the adsorption process. The effect of shear rate is investigated under laminar conditions in a Couette flow. Stationary and sinusoidally modulated values of the shear rate are imposed over the (0-200 s-1) range. The flow conditions are shown to play an essential role by markedly modifying the rate of all the steps (three at most) involved in the adsorption mechanism. Moreover, the structure of the adsorbed layers in the intermediate and final states are also strongly modified, an increase of the shear rate increasing the interaction between the protein and the electrode. Piezoelectric properties of albumin are invoked to account for the experimental results.

[AN 69 membrane and conversion enzyme inhibitors: prevention of anaphylactic shock by alkaline rinsing?]. / Membrane AN 69 et inhibiteurs de l'enzyme de conversion: prévention des chocs anaphylactoïdes par le rinçage alcalin?

Thirty-three anaphylactoid reactions occurring in 19 ACE inhibitors-treated patients dialyzed with AN 69 membrane--plate and hollow fibers--dialyzers are reported. A careful analyze of these observations strongly suggests the preventive role of alkaline rinsing of the membrane.

[Vertebral involvement and fetal alcohol syndrome]. / Atteintes vertébrales et syndrome d'alcoolisme foetal.

Vertebral abnormalities observed in 8 children with fetal alcohol syndrome are described and discussed. They include scoliosis (4 cases), neural tube defects (4 cases) and complex malformations of the cervical spine (2 cases). The latter probably constitute a different entity from that of the Klippel-Feil syndrome. It is probable that alcohol plays a direct role in the genesis of these abnormalities.

Polyadenylic-polyuridylic acid as adjuvant in the treatment of operable breast cancer: recent results.

A randomized trial of polyadenylic-polyuridylic acid (Poly(A).Poly(U) given as an adjuvant in the treatment of operable breast cancer, has included 300 patients of the Institut Gustave-Roussy from September 1972 to December 1979; 145 patients were allocated to conventional treatment alone and 155 to conventional treatment plus Poly(A).Poly(U). Reviews after mean periods of follow-up of 50 and 87 months were previously published. The present review performed after a mean follow-up period of 111 months confirmed a significant increase in the overall survival of patients with invaded nodes treated with Poly(A).Poly(U). The best results were achieved in the subset of patients with up to three affected nodes who showed a significant increase of both overall and relapse-free survival. The benefit seemed to be greater in postmenopausal women (P = 0.07). Present status of other ongoing trials of adjuvant Poly(A).Poly(U) is presented.

Polyadenylic-polyuridylic acid: biological response-modifying activities in mice. In vivo organ distribution and pharmacokinetics in rabbits.

Lack of toxicity of polyadenylic-polyuridylic acid [poly(A).poly(U)] in rodents is demonstrated. This immunomodulator has antitumor activity when used as an adjuvant to surgery or to chemotherapy. Biological mediator properties that shed some light on the mechanism of tumor inhibition are the potentiating effects of poly(A).poly(U) on T cells, natural killer cells, and interferon activity as indicated by the level of the enzyme 2-5 A synthetase. In vivo organ distribution and pharmacokinetic studies in rabbits by a scintigraphic technique, subcellular fractionation, and sucrose sedimentation profiles indicate a surprising metabolic stability (measured in days).

Poly(A).poly(U) as adjuvant in cancer treatment distribution and pharmacokinetics in rabbits.

Rabbits were injected with poly(A).poly(U) and the metabolic fate and stability studied using scintigraphic techniques, radioactive counting, and subcellular fractionation. The complex has a very long lifetime (measured in days) in both liver and spleen, the major locations of concentration in the animal, with about nine times more per gram of tissue in the spleen compared with the liver. In spleen cells the material is about equally divided between nuclei and cytoplasm. The polymer is slowly degraded to shorter molecules in these cells but, even 1 week after injection, significant amounts of apparently intact polynucleotide complex can be detected in both cellular fractions.