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Biomedical subjects

R Bouillon

Publications and source records attributed to R Bouillon.

At least 217 records · Page 12Linked to original sources

C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in umbilical cord serum: correlations with birth weight.

OBJECTIVE: Our purpose was to determine the correlation between birth weight and hormones or growth factors believed to be involved in fetal growth: insulin, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1. STUDY DESIGN: Five hundred thirty-eight cord serum samples were analyzed for insulin-like growth factor-I, insulin-like growth factor-II, C-peptide, and insulin-like growth factor binding protein-1 by immunoassay. Samples included all gestational ages in the third trimester and a large range of birth weights. RESULTS: Cord serum insulin-like growth factor-I concentrations increased until 39 weeks (+84% from 28 to 29 weeks), followed by a 21% decline at 41 weeks. Insulin-like growth factor-I levels were decreased by 40% in small-for-gestational-age (< 10th percentile) newborns and were increased by 28% in large-for-gestational-age (> 90th percentile) newborns in the absence of diabetes. Insulin-like growth factor-I levels were best correlated with birth weight (R = 0.48, p < 0.001). Cord serum insulin-like growth factor-II concentrations were sixfold to tenfold higher than those of insulin-like growth factor-I and were 8% to 10% (p < 0.001) higher in large-for-gestational-age than in average-weight and small-for-gestational-age newborns. Cord serum C-peptide concentrations were 28% and 34% higher in large-for-gestational-age than in average-for-gestational-age and small-for-gestational-age newborns, respectively. Insulin-like growth factor binding protein-1 levels were increased in preterm average-for-gestational-age and in term small-for-gestational-age newborns compared with term average-for-gestational-age newborns and showed a negative correlation with birth weight (R = -0.43, n = 131, p < 0.001). Insulin-like growth factor binding protein-1 was not correlated with C-peptide concentrations. CONCLUSIONS: Insulin-like growth factors I and II and insulin are all related to fetal growth and weight gain, and insulin-like growth factor-I correlates best with birth weight. Insulin is mainly related to fetal overgrowth (macrosomia). Insulin-like growth factor binding protein-1 may be a growth inhibitor in the fetus.

Adult↗

The measurement of fecal thyroxine in the diagnosis of thyrotoxicosis factitia.

Two patients with prolonged thyrotoxicosis are presented with low radioiodide uptake, low-normal serum thyroglobulin concentrations, and low iodide content of the neck on x-ray fluorescence studies. The surreptitious intake of thyroid hormone was directly proven by a high fecal concentration of T4 (12.38 and 23.99 nmol/g) compared with low concentrations in healthy subjects (1.03 +/- 0.64 nmol/g; mean +/- SD, n = 6) and in patients with hyperthyroidism due to Graves' disease (1.93 +/- 1.86; n = 8). Fecal thyroid hormone measurement may help to provide formal proof of factitious thyrotoxicosis.

Adult↗

Calcium metabolism, plasma parathyroid hormone, and calcitriol in transient hypertension of pregnancy.

In order to know if abnormalities of calcium metabolism may be involved in the pathophysiology of pregnancy-induced hypertension (PIH), as it has been incriminated in essential hypertension, we measured plasma and urinary calcium and phosphate as well as plasma PTH and free calcitriol index (ratio of total calcitriol on the D binding protein) in normotensive pregnant women (n = 25), in women with PIH after the same duration of amenorrhea (> 28 wk, n = 21:preeclampsia and 20 transient hypertensions), and in age-matched nonpregnant women (n = 15). The severity of PIH was mild since blood uric acid was not increased and plasma volume, measured with the Evans blue technique, was found only moderately decreased (-10.5 +/- 3.1% of normal value). The results show that normotensive pregnant women showed the expected increase of the vitamin D parameters in comparison to nonpregnant controls. Hypertensive pregnant women were not different from the normotensive ones regarding plasma corrected calcium and phosphate and urinary excretion of calcium and phosphate, but had higher plasma PTH (13 +/- 1 v 8.8 +/- 1.6 pg/mL) and lower total and free calcitriol index (86 +/- 7 v 110 +/- 6 pg/mL and 1.72 +/- 0.10 v 2.25 +/- 0.13 x 10(-5)). Correlative studies showed PIH having a negative correlation between blood pressure and plasma corrected calcium (r = -0.43, P < .05), which is in agreement with epidemiological studies of essential hypertension. In conclusion, disturbances of calcium regulating hormones do exist in transient forms of pregnancy-induced hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Erythrocyte cation transport systems and membrane lipids in insulin-dependent diabetes.

The relationship between erythrocyte cation transport systems and membrane and plasma lipids was examined in normal men and patients with insulin-dependent diabetes mellitus (IDDM). Different measurements of erythrocyte transport systems were obtained in patients with IDDM and in age- and weight-matched healthy men: Na+:Li+ countertransport activity or Li(+)-stimulated Na+ efflux, Na+:K+ cotransport activity or bumetanide-sensitive Na+ efflux, Na+:K+ pump activity or ouabain-sensitive Na+ efflux, and the ouabain- and bumetanide-resistant Na+ and K+ fluxes or the ground membrane permeability for Na+ and K+ as well as the intraerythrocyte Na+, K+, and Mg2+ concentrations. Plasma cholesterol, triglycerides, phospholipids, low- and high- density lipoprotein cholesterol, and erythrocyte membrane cholesterol and phospholipid content were obtained from the fasting subjects. The patients with IDDM had an elevated (P < .05 or less) erythrocyte Na+:Li+ countertransport activity, ground membrane leak for K+, intraerythrocyte K+ concentration, and erythrocyte membrane cholesterol content, but a lower red blood cell phospholipid content. In single regression analysis, the erythrocyte Na+:Li+ countertransport, Na+:K+ cotransport, and Na+:K+ pump activity and ground membrane leak for Na+ and K+ were inversely related to the red blood cell membrane lipid content. Our data in patients with IDDM show that a decreased erythrocyte membrane lipid content was accompanied by a higher erythrocyte Na+:Li+ countertransport, Na+:K+ cotransport, and Na+:K+ pump activity.

Adult↗

Partial prevention of active Heymann nephritis by 1 alpha, 25 dihydroxyvitamin D3.

The hormone 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) has potent immunosuppressive effects in vitro. Recent publications also described a protective effect of the hormone in various animal models of immune-mediated diseases. To test its in vivo activity we induced active Heymann nephritis in Lewis rats that were either untreated or treated with 1,25(OH)2D3 or its synthetic 20-epi analogue, KH1060. Treatment with cyclosporine A (CsA) was used as an immunosuppressive control. In this nephrotic model the administration of 1,25(OH)2D3 (0.5 microgram/kg body weight) given on alternate days during the first 13 days after active immunization significantly reduced the proteinuria as measured by weeks 7-9. This reduction was comparable to the reduction observed in rats treated with CsA (20 mg/kg) on alternate days. A second series of experiments with 1,25(OH)2D3 confirmed these findings. The level of autoantibodies was found to be significantly suppressed during the treatment time in the CsA (20 mg/kg) group, whereas the limit of significance (P = 0.06) was reached in the 1,25(OH)2D3 (0.5 microgram/kg) group. The size of the immune deposits also was found to be substantially smaller in the groups that developed less proteinuria. The administration of 1,25(OH)2D3 transiently increased the mean serum calcium concentration with 2.5 mg/dl above the pretreatment values, and the urinary calcium excretion by a factor of 3-5 during the short treatment time. Treatment with the analogue KH1060 did not reduce the proteinuria significantly. Our experiments add evidence to the hypothesis that 1,25(OH)2D3 in pharmacological doses has immunosuppressive potency.

Animals↗

Five-year follow-up of growth hormone antibodies in growth hormone deficient children treated with recombinant human growth hormone.

OBJECTIVE: The aim was to investigate the long-term evolution of circulating growth hormone antibodies (GH-AB) during and after treatment with methionyl-recombinant human growth hormone (met-rhGH). DESIGN AND PATIENTS: The investigation was performed on serum samples of 46 growth hormone deficient children, treated for at least 12 months with met-rhGH. Twenty patients had never been treated with hGH (previously untreated patients, Group I). Twenty-six subjects were previously treated with pituitary extracted hGH (treated patients, Group II). MEASUREMENTS: Serum levels of GH-AB were measured by radioimmunoassay using charcoal precipitation of free ligand. RESULTS: Fifteen patients (75%) of Group I and three patients (12%) of Group II developed GH-AB. In 15 GH-AB positive patients the antibodies became detectable during the first year of treatment with met-rhGH. In three patients, however, the GH-AB appeared during the second year. Once present, the GH-AB remained detectable throughout the period of treatment with met-rhGH. In six patients in whom treatment with met-rhGH was stopped, GH-AB levels decreased rapidly. In nine patients in whom treatment with met-rhGH was changed to rhGH, the levels of GH-AB decreased and ultimately became undetectable. In two patients GH-AB remained present during administration of rhGH. No effect of GH-AB on the growth-promoting effect of met-rhGH could be documented, either during the first or during the second year of treatment. CONCLUSIONS: This study confirms the high immunogenicity of met-rhGH, especially in patients not treated earlier with hGH. Once present, the GH-AB remain detectable throughout the period of treatment with met-rhGH. After stopping met-rhGH treatment or changing to rhGH the GH-AB disappear rapidly in most patients. No effect of GH-AB on the growth-promoting effect of rhGH could be documented.

Adolescent↗

Increased clearance of 1,25(OH)2D3 and tissue-specific responsiveness to 1,25(OH)2D3 in diabetic rats.

The kinetics of 1,25-dihydroxyvitamin D3 [1,25(OH)2-D3] and the in vivo response to 1,25(OH)2D3 (7.5, 15, and 30 ng/100 g body wt), infused or injected subcutaneously for 12-14 days, were studied in male spontaneously diabetic and control BB rats. In control rats, increasing doses of 1,25(OH)2D3 produced parallel increases in plasma 1,25(OH)2D3 and calcium, urinary calcium, duodenal CaBP9K, and renal CaBP28K. 1,25-(OH)2D3 at 30 ng/100 g markedly raised plasma osteocalcin and osteoblast/osteoid surfaces in the tibial metaphysis, but inhibited bone mineralization rate. In diabetic rats, plasma 1,25-(OH)2D3 concentrations were decreased, and the rise of plasma 1,25(OH)2D3 during 1,25(OH)2D3 infusion was blunted, but the free 1,25(OH)2D3 index remained normal or above normal. Diabetic rats had an increased metabolic clearance rate of 1,25-(OH)2D3 (0.38 +/- 0.015 vs. 0.24 +/- 0.007 ml.min-1.kg-1), with no further increase in 1,25(OH)2D3-infused diabetic rats; their relative production rate of 1,25(OH)2D3 was unchanged. The responses of plasma and urinary calcium, duodenal CaBP9K, and renal CaBP28K to infused 1,25(OH)2D3 were normal, as was duodenal calcium absorption in 1,25(OH)2D3-injected diabetic rats. However, the virtual absence of osteoblasts/osteoid in trabecular bone was unaltered in diabetic rats infused with 30 ng/100 g 1,25(OH)2D3, with only minimal increase of their low plasma osteocalcin levels. 1,25(OH)2D3 treatment therefore cannot be expected to reverse diabetic osteopenia.

Animals↗

Effects of sex steroids on hepatic and lipoprotein lipase activity and mRNA in the rat.

In humans, sex steroids have been implicated in the regulation of hepatic and lipoprotein lipase activity. Therefore, the effects of orchidectomy and subsequent androgen or estrogen administration on hepatic lipase (HL) and adipose tissue and heart lipoprotein lipase (LPL) were examined. Relative to intact controls, orchidectomy of male rats resulted in no significant change in HL activity and mRNA, or in heart and adipose tissue LPL activity and mRNA levels. Subsequently, a subcutaneous silastic tubing, delivering either testosterone, dihydrotestosterone, nandrolone, or 17 beta-estradiol, was implanted for 5 weeks. All substitution treatments had a tendency to reduce HL activity and to induce HL mRNA levels. This effect was, however, only significant for testosterone which resulted in a decrease in HL activity (238 +/- 15 vs. 328 +/- 31 mU/g tissue; p vs. control < 0.05) and an increase in HL mRNA (166 +/- 11 vs. 100 RAU; p vs. control < 0.01). No significant effects of androgens on LPL expression either in heart or adipose tissue were observed. Adipose tissue LPL activity (20 +/- vs. 35 +/- 4 mU/g; p vs. control < 0.05) and mRNA (28 +/- 4 vs. 100 RAU; p vs. control < 0.001) levels, but not heart LPL, however, were diminished substantially after 17 alpha-estradiol treatment. In conclusion, rat HL is influenced by testosterone, while adipose tissue, but not heart LPL, is reduced after estrogen administration.

Adipose Tissue↗

A comparison between the diagnostic value of gonadotropins, alpha-subunit, and chromogranin-A and their response to thyrotropin-releasing hormone in clinically nonfunctioning, alpha-subunit-secreting, and gonadotroph pituitary adenomas.

We tested the hypothesis of whether chromogranin-A (CGA), an immunohistochemical marker of neuroendocrine tumors, could serve as a serum marker for clinically nonfunctioning pituitary adenomas. Basal and TRH-stimulated concentrations of LH, FSH, alpha-subunit, and CGA were measured in 22 patients with clinically nonfunctioning pituitary adenomas and in 20 control patients with other pituitary tumors. The control group consisted of 9 patients with PRL- and/or GH-secreting adenomas and 11 patients with nonendocrine tumors [5 craniopharyngiomas, 2 (dys)germinomas, 1 astrocytoma, 1 meningioma, 1 neurinoma of the acoustic nerve, and 1 dermoid cyst]. Immunohistochemical staining for CGA was performed on tumor tissue obtained at transsphenoidal surgery in 18 study and 12 control patients. Tissue from 19 of the 22 clinically nonfunctioning adenomas was cultured, and concentrations of LH, FSH, alpha-subunit, and CGA were measured. Immunohistochemical staining for CGA was positive in 15 of 18 clinically nonfunctioning adenomas and negative in all examined control tumors (n = 12). CGA was present in the culture medium of 16 of 18 adenomas in vitro. In 3 adenomas it was present in the absence of detectable amounts of gonadotropins or alpha-subunit. Basal serum levels of gonadotropins and/or alpha-subunit were elevated in 7 of 22 patients with clinically nonfunctioning adenomas and in 4 of 9 control patients with PRL- and/or GH-secreting adenomas. Basal CGA was elevated in 2 study patients and 1 prolactinoma patient. Significant increases in serum gonadotropin and/or alpha-subunit levels in response to TRH occurred in 14 of 21 patients with clinically nonfunctioning adenomas and in 13 of 20 control patients. A significant CGA peak after TRH administration was demonstrated in 6 patients with clinically nonfunctioning pituitary tumors and in none of the controls. We conclude that 1) immunohistochemical staining for CGA is an excellent tool to prove the endocrine origin of clinically nonfunctioning pituitary tumors; 2) in vivo, the gonadotroph origin can be recognized in only a minority of patients who have elevated basal levels of LH, FSH, or alpha-subunit; 3) examination of the effect of TRH on CGA release is a rather insensitive, but specific, diagnostic test, allowing differentiation from nonendocrine pituitary tumors; and 4) the responses of gonadotropins and alpha-subunit to TRH, although more sensitive, are not specific for clinically nonfunctioning pituitary adenomas and are probably only reliable in cases of total hypopituitarism.

Adenoma↗

Lack of disease recurrence in diabetic BB/Pfd rats after syngeneic islet transplantation.

Restimulation of autoreactivity in two different BB rat sublines of the same origin (Ottawa, Canada) was investigated by syngeneic islet transplantation into diabetic animals. Despite identical methods and conditions recurrence of hyperglycaemia was observed in BB/OK rats (Karlsburg, Germany) but not in BB/Pfd rats (Leuven, Belgium). Pancreatic morphology at the time of transplantation revealed significant differences in islet volume density and the degree of insulitis. Additionally, marked differences in the phenotypical composition of cells infiltrating the islets were observed. A loss of autoimmune memory in BB/Pfd rats is discussed as a probable reason for the lack of disease recurrence in those animals.

Animals↗

Characterization of gastric antral motility disturbances in diabetes using a scintigraphic technique.

In this study, food distribution in the stomach and gastric antral motor activity in patients with longstanding diabetes have been evaluated. With use of a standard gastric emptying test with an acquisition protocol and a refined Fourier algorithm to analyze the data, antral contractions have been characterized and gastric motility parameters were correlated to gastric retention in 20 diabetic patients with or without gastroparesis and in 10 healthy subjects. The results of this study show that, in longstanding diabetes, gastric emptying retardation is accounted for by a retention of food in the proximal stomach, which is reflected by a prolonged lag phase as well as by a reduction in antral motor activity that is determined by a decrease in the amplitude of the antral contractions. This study demonstrates that scintigraphy can noninvasively characterize abnormalities of food distribution in the stomach and provides information similar to that obtained from manometry.

Adult↗

[Quality of induction and adrenocortical function. A clinical comparison of Etomidate-Lipuro and Hypnomidate].

UNLABELLED: The purpose of this study was to compare etomidate in a lipid emulsion (Etomidat-Lipuro; Braun, Melsungen) and in propylene glycol (Hypnomidate, Janssen Pharmaceutica) in 90 patients in terms of anaesthetic induction characteristics with special reference to injection side effects, haemodynamic changes, and quality of induction. Adrenocortical hormones were determined in 30 patients who received either Etomidat-Lipuro, Hypnomidate, or propofol (Diprivan, ICI Pharma) for induction of anaesthesia. METHODS: One hundred twenty patients gave their informed consent to the study. In the first part, 90 patients were assigned at random to two groups in which induction of anaesthesia was performed either with Etomidat-Lipuro or Hypnomidate. Anaesthesia was started by i.v. injection of 25 micrograms/kg alfentanil (Rapifen, Janssen Pharmaceutica). One minute later, the hypnotic agent was injected into a freely running i.v. line (18 Gcannula) that was used only for the hypnotic and was removed 15 min later. During injection, the patients were asked to inform the anaesthesiologist spontaneously and on request about their sensations at the injection site. The time from the beginning of anaesthesia until the disappearance of the eyelash reflex was measured. The patients were ventilated and vecuronium was administered to allow good intubation conditions 2-3 min later. For the first 10 min, blood pressure and heart rate were measured every minute. Postoperatively, the same investigator made rounds once a day and examined the injection sites. Signs of pain, redness, swelling, induration, thrombophlebitis, or thrombosis were noted. In the second part of the study, 30 patients were investigated for endocrinological changes after induction of anaesthesia with Etomidat-Lipuro, Hypnomidate, or Diprivan. The patients were allocated to the groups at random. A radial artery catheter was inserted in every patient. Sampling took place 30 min before and 1 and 2 h after induction. Additional samples were drawn 30 min and 1, 2, and 22 h after i.v. administration of 0.25 mg ACTH (Synacthen, Ciba-Geigy). The plasma concentrations of cortisol, 17 alpha-OH-progesterone, and aldosterone and the renin activity were determined by high-performance liquid chromatography. RESULTS: The loss of the eyelash reflex occurred 42.9 +/- 8.7 and 42.2 +/- 11.0 s after the administration of Etomidat-Lipuro and Hypnomidate. The haemodynamic changes were minimal in both groups. After administration of alfentanil, local side effects of the hypnotics were scarce, with a tendency to be weaker and more seldom after Etomidat-Lipuro (3/55 versus 8/55). The postoperative vein reactions were generally mild and occurred in 17 out of 55 patients after Etomidat-Lipuro and 15 out of 55 patients after Hypnomidate. In most cases these signs were no longer present on the 2nd day after the procedure. Cortisol levels were depressed initially by all the hypnotic drugs used. While there was spontaneous recovery in the Diprivan group after 2 h combined with a positive overshooting response to ACTH stimulation, in the etomidate groups cortisol could not be stimulated; it normalized slowly during the following 24 h. The 17 alpha-OH-progesterone increase was significant in the etomidate groups after the administration of ACTH. The aldosterone levels decreased after etomidate injection and had not normalized 24 h later, while there was a normal response to ACTH in the propofol group. There was a normal decrease in renin activity in all three groups after the administration of ACTH. CONCLUSION: Local side effects are minimal after the administration of Etomidat-Lipuro and Hypnomidate. Alfentanil reduces the injection pain of etomidate induction agents. Cortisol and aldosterone are depressed by etomidate, but the clinical relevance is minimal after a single bolus injection.

Adolescent↗

Vanadate potentiates the glycogenic action of insulin-like growth factors on isolated diaphragm.

Na3VO4 (6.5 mumol/100 g rat weight), co-injected with a trace amount of [14C]glucose, increased within 15 min the incorporation of radiolabel in diaphragmal glycogen. After 2 h the vanadate-induced increases were 12-fold in the diaphragm and 7-8-fold in heart and liver. In contrast, when added to isolated diaphragms for up to 1 h, vanadate (0.1-5 mM) had no effect on the synthesis of glycogen from 5 mM glucose. In search of a putative mediator of vanadate's action in vivo, insulin and the insulin-like growth factors (IGFs) were considered. Their plasma concentration was not affected by vanadate treatment. In isolated diaphragms, 1 mM vanadate did not potentiate insulin-induced glycogen synthesis, but it caused a several-fold increase in glycogen synthesis in the presence of concentrations of IGF-I which, alone, had no effect. A similar synergism occurred between vanadate and IGF-II. We propose that the glycogenic action of vanadate in vivo, at least in some tissues, involves a potentiation of the action of IGF-I.

Animals↗

Structure function analysis of vitamin D analogs with C-ring modifications.

Analogs of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) with substitutions on C-11 were synthesized. Small apolar substitutions (11 alpha-methyl, 11 alpha-fluoromethyl) did not markedly decrease the affinity for the vitamin D receptor, but larger (11 alpha-chloromethyl or 11 alpha- or 11 beta-phenyl) or more polar substitutions (11 alpha-hydroxymethyl, 11 alpha-(2-hydroxyethyl] decreased the affinity to less than 5% of that of 1 alpha,25-OH)2D3. Their affinity for the vitamin D-binding protein, however, increased up to 4-fold. The biological activity of 11 alpha-methyl-1 alpha,25-(OH)2D3 closely resembled that of the natural hormone on normal and leukemic cell proliferation and bone resorption, whereas its in vivo effect on calcium metabolism of the rachitic chick was about 50% of that of 1 alpha,25-(OH)2D3. The 11 beta-methyl analog had a greater than 10-fold lower activity. The differentiating effects of the other C-11 analogs on human promyeloid leukemia cells (HL-60) agreed well with their bone-resorbing activity and receptor affinity, but they demonstrated lower calcemic effects in vivo. Large or polar substitutions on C-11 of 1 alpha,25-(OH)2D3 thus impair the binding of the vitamin D receptor but increase the affinity to vitamin D-binding protein. The effects of many C-11-substituted 1 alpha,25-(OH)2D3 analogs on HL-60 cell differentiation exceeded their activity on calcium metabolism.

Animals↗

Bone and mineral metabolism in the adult guinea pig: long-term effects of estrogen and androgen deficiency.

The effects of androgen and estrogen deficiency on skeletal homeostasis were studied in the guinea pig. Male and female adult (7 months old) guinea pigs were either sham operated (9 females and 7 males) or gonadectomized [9 ovariectomized (OVX) females and 6 orchidectomized (ORX) males] and sacrificed 4 months later for evaluation of bone mass, bone turnover, and serum calcium homeostasis. Parameters of bone turnover, calcium homeostasis, and vitamin D metabolites were similar in all groups except for increased serum IGF-I concentrations (+30%) in males compared to females. Gonadectomy resulted in a 50% decrease in serum IGF-I concentrations in males only (p < 0.001). Volume, total calcium content, and cortical density of the tibia were significant higher in males than in females. Estrogen deficiency had no effect on bone volume or calcium content. Androgen deficiency resulted in a significant lower volume and calcium content of the tibia and in a lower calcium content of the distal lumbar vertebrae. Single-photon absorptiometry of the tibia showed that only cortical, not trabecular bone density of the tibia was decreased after ORX. Histomorphometric studies of the tibial metaphysis also did not show significant differences in trabecular bone volume between sham-operated and ORX males. We conclude that in adult male guinea pigs androgen deficiency results in a decrease in (cortical) bone volume and content concomitant with decreased IGF-I levels. In female guinea pigs of the same age, estrogen deficiency did not affect total or regional bone mass.

Absorptiometry, Photon↗