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At least 649 records · Page 36Linked to original sources
PubMed2000

A sustained, non-insulin related, hypoglycaemic effect of electroacupuncture in diabetic Psammomys obesus.

AIM/HYPOTHESIS: Electroacupuncture has been shown to induce a short-term hypoglycaemic effect in streptozotocin diabetic rats. We designed an experiment to investigate the effect of electroacupuncture in Psammomys obesus, a model of insulin resistance and non-insulin-dependent diabetes mellitus. METHODS: We divided 29 diabetic Psammomys randomly into three groups: abdominal electroacupuncture (real, n = 11), back electroacupuncture (placebo, n = 9) and control (anaesthesia, n = 9). Electroacupuncture was carried out on days 1, 3 and 5 of the experiment. During the first week of the experiment, blood glucose was tested three times on treatment days and once on the following days. Over the next 2 weeks, blood glucose was tested every other day. Animals were weighed at the same time of blood sampling. After 3 weeks, at the end of the experiment, blood was drawn for measurement of insulin, fructosamine, cholesterol and triglycerides. RESULTS: At day 5 (end of intervention), blood glucose (as per cent of primary concentrations, means +/- SE) was 57 +/- 10, 93 +/- 13 and 89 +/- 11 for the real, placebo and control groups respectively (p = 0.02). At day 8, blood glucose 68 +/- 14, 86 +/- 16 and 97 +/- 9 for the real, placebo and control groups respectively (p = 0.04). At day 22, blood glucose was 79 +/- 11, 85 +/- 15 and 131 +/- 2 for the real, placebo and control groups (p = 0.04). Comparison of the decline in blood glucose, throughout the 3 weeks, between the real and placebo groups by ANOVA was highly significant (p < 0.0001), the difference between the placebo and control groups at the same time was not significant (p > 0.05). Animal weight gain, serum insulin, fructosamine, cholesterol and triglycerides were not significantly different between real and placebo groups. CONCLUSION/INTERPRETATION: Electroacupuncture at special abdominal acupoints induces a sustained hypoglycaemic effect in diabetic Psammomys compared with electroacupuncture at non-specific points, without weight loss. No hypoinsulinaemic effect was shown in the real and placebo groups.

Analysis of Variance↗
PubMed1999

An open comparison of the diabetogenic effect of deflazacort and prednisone at a dosage ratio of 1.5 mg:1 mg.

OBJECTIVE: To compare the diabetogenic effects of deflazacort (D) versus prednisone (PN) using a dosage ratio of 1.5 mg deflazacort:1 mg prednisone. METHODS: Thirty-three patients suffering from various active connective tissue or chronic inflammatory diseases were randomized to be treated with D or PN, assuming a therapeutic equipotency ratio of 1.5 mg D:1 mg PN. Neither dosage nor glucocorticoid employed were modified during the study. Patients had not received steroid treatment during the month prior to their inclusion date. Fasting glucose, glycosylated haemoglobin and fructosamine were determined before and after 1 month of treatment. Non-diabetic patients were also submitted to an oral glucose tolerance test (OGTT) at entry and after 1 month. Results were compared by univariate, and multivariate tests to correct the effects of age, body mass index and diagnosis. RESULTS: After 1 month of treatment there were no differences between D and PN in fasting glucose, glycosylated haemoglobin, or fructosamine. OGTT performed after treatment showed similar glucose values for both treatment groups. Patients treated with D had insulin levels at min 60 of the post-treatment OGTT which were higher than those treated with PN [114.1 (62.8) mcUI x ml(-1) versus 73.5 (32.7) mcUI x ml(-1), P = 0.049], but the difference lost its statistical significance in the multivariate analysis. CONCLUSION: D and PN have similar effects on glucose tolerance when an equipotency ratio of 1.5 mg D:1 mg PN is employed. Previous studies employing a ratio of 1.2:1 mg may have underestimated the adverse effects of D on glucose metabolism.

Anti-Inflammatory Agents↗
PubMed1998

Electronegative low density lipoprotein subform (LDL-) is increased in type 2 (non-insulin-dependent) microalbuminuric diabetic patients and is closely associated with LDL susceptibility to oxidation.

There is increasing evidence that diabetes mellitus is characterized by an enhanced lipoprotein oxidation. We have therefore investigated whether a relationship exists between LDL oxidation and microalbuminuria, which is considered an early marker of vascular involvement in type 2 diabetic patients. We selected 12 microalbuminuric and 12 normoalbuminuric type 2 diabetic patients, and 12 control subjects comparable for age, sex and blood pressure values. Oxidatively modified plasma LDL, referred as LDL-, were measured by ion-exchange HPLC. In vitro susceptibility to oxidation of LDL was evaluated by following the kinetics of conjugated diene formation in the presence of Cu++ ions (lag-phase time). Microalbuminuric diabetic patients had a less satisfactory metabolic control and showed a higher plasma triglyceride concentration than both normoalbuminuric diabetic patients (2.211+/-1.01 vs 1.15+/-0.39 mmol/l, P<0.O1) and controls (1.18+/-0.61 mmol/l, P<0.01 ). The percentage of LDL- in plasma was significantly increased in microalbuminuric diabetic patients in comparison with both normoalbuminuric diabetic patients (5.24+/-1.67 vs 3.13+/-1.22%, P<0.01) and controls (2.34+/-1.03%, P<0.001). LDL isolated from microalbuminuric diabetic patients had a significantly shorter lag-phase time in comparison with normoalbuminuric diabetic patients (79+/-11 vs 97+/-10 min, P<0.05) and controls (120+/-24 min. P<0.001). In diabetic patients a significant linear correlation was observed between the percentage of LDL and amount of fructosamine (r=0.45, P<0.05), HbA1c (r=0.41, P<0.05), and triglycerides (r=0.65, P<0.001). An inverse correlation was found between lag-phase time and fructosamine (r=-0.5, P<0.01) and triglycerides (r=-0.59, P<0.001). This study shows that microalbuminuric type 2 diabetic patients had evidence of increased LDL oxidation, which seems to be mainly due to a poor metabolic control and a more atherogenic lipid profile.

Aged↗
PubMed2005

Glycated hemoglobin and liver disease in diabetes mellitus.

Glycated hemoglobin (GHb) measured as HbA1c in diabetic patients, is used to evaluate long-term control of diabetes mellitus, and most accurately reflects the previous 2-3 months of glycemic control. Liver disease is one of the leading causes of death in persons with type 2 diabetes mellitus. Diabetic patients can present with abnormal liver chemistries, from benign nonalcoholic fatty liver disease to severe cirrhosis of the liver. Because liver disease is associated with impaired glucose tolerance and diabetes mellitus, tools are needed to measure long-term glycemic control. In this review we discuss current information on glycated hemoglobin, HbA1c assay methods, attempts to standardize HbA1c assay methods, fructosamine and interferences caused by liver disease. We aim to alert the reader to current problems in determining long-term glycemic control parameters, HbA1c and fructosamine, and describe the measures necessary for proper interpretation of HbA1c.

Cause of Death↗
PubMed1986

The measurement of glycosylated albumin by reduction of alkaline nitro-blue tetrazolium.

A method is described for the measurement of glycosylated albumin in human plasma. Purification of albumin is achieved by a simple one-step chromatographic method, adapted for use as a batch analysis technique. The glycosylated albumin fraction is subsequently measured by a modification of the fructosamine assay (alkaline reduction of nitroblue tetrazolium). The method correlates with the plasma fructosamine assay (r = 0.85; p less than 0.001) and with an electrophoretic method for the measurement of HbA1 (r = 0.78; p less than 0.001).

Chromatography↗
PubMed1991

Abnormal serum immunoglobulin concentrations in patients with diabetes mellitus.

Since the recently reported relationship between serum fructosamine and IgA concentrations appears to throw doubt on the clinical utility of fructosamine as a measure of hyperglycemic status if IgA concentration is not taken into account, we studied serum immunoglobulin concentrations in 169 diabetics and their relationship with various clinical and analytical parameters. Over 41% of the patients studied had abnormal serum IgA concentrations. Serum IgA concentration was negatively correlated with serum albumin, and among IDDM patients was positively correlated with age (so that the prevalence of abnormal IgA was 57.7% among IDDM patients aged over 30 years). Among NIDDM patients, abnormal IgA concentrations were especially prevalent among those being treated with oral hypoglycemics. Abnormal IgA was also more frequently found in both IDDM and NIDDM patients, who had been under treatment for 10 years or more. Abnormal IgG concentrations were found in 11.8% of the diabetics, and the mean IgM concentration found in the patients was 41.6% lower than in the normoglycemic group. We conclude that abnormal serum IgA concentrations are very common in diabetic patients and that further research should be carried out to verify whether the determination of serum immunoglobulins, IgA in particular, is of clinical use for monitoring diabetes or evaluating its secondary effects.

Adolescent↗
PubMed1992

Measurement of glycated albumin by the nitroblue tetrazolium colorimetric method.

A method has been developed for the measurement of glycated albumin (albumin-fructosamine) by the nitroblue tetrazolium (NBT) colorimetric method. In this method, polyethylene glycol was added to the serum and then the mixture was centrifuged to separate globulin proteins from albumin proteins. This made it possible to measure the glycated albumin in the supernatant by the NBT colorimetric method, without the interference of globulin proteins. This measurement method correlated with the measurement of glycated albumin using boronate affinity chromatography with an r value of 0.942 (P < 0.001). Our method using polyethylene glycol permits easy measurement of albumin fructosamine and is therefore useful as an index of diabetic control and for diabetic screening.

Chromatography, Affinity↗
PubMed1993

Aminoguanidine inhibits protein browning without extensive Amadori carbonyl blocking.

It has been proposed that aminoguanidine reacts extensively with Amadori carbonyl groups of glycated proteins thus blocking them and inhibiting the further reactions which lead to browning and fluorescence development. We have glycated bovine serum albumin in the presence of 1, 5, 10 and 25 mM aminoguanidine and measured fluorescence development at 440 nm upon excitation at 370 nm, free (unblocked) Amadori groups as fructosamine with a colorimetric assay and furosine by HPLC, as an index of total Amadori products. Aminoguandine significantly inhibited fluorescence development at all the tested concentrations (31%, 65%, 69% and 82% inhibitions, respectively) (P < 0.001). Blocking of Amadori groups was demonstrated by decreased fructosamine and unchanged furosine yields but only at the higher concentrations and to a very limited extent (13% and 27% blocking, respectively) (P < 0.01). Incubation of Aminoguanidine with albumin produced the appearance of 320 nm absorbing yellow chromophores, quite increased in the presence of glucose. These results suggest that Aminoguanidine is able to block Amadori groups, as previously hypothesized, but question the importance of this mechanism as an explanation of its capacity to inhibit browning. Scavenging of glucose seems to have no impact on glycation as seen by unchanged furosine yields.

Animals↗
PubMedDate not supplied

Computer models of albumin and haemoglobin glycation.

UNLABELLED: Two first-order mathematical models were developed to mimic the glycation of haemoglobin (H) and albumin (A). The total concentrations of A and H were assumed to be constant. The responses of the two models to varying blood glucose level were compared. The parameters of the haemoglobin model were not numerically estimated, only an informal fit was performed using clinical and published data. Nonlinear regression analysis was used to estimate the parameters of the albumin model. The level of glycated A (GA) was derived from the measured fructosamine level. Three diabetics were monitored daily for the level of fructosamine and blood glucose profile over a period of 10, 16 and 21 days, respectively. CONCLUSIONS: (1) The difference between GA and glycated H (GH) resulting from different elimination rates is decreased by the stratification of erythrocyte population. (2) Both GA and GH seem to have higher elimination rates than their nonglycated equivalents.

Blood Glucose↗
PubMed1990

Changes in glycosylated proteins in long-term complications of diabetes mellitus.

Increased glycosylation of various proteins in diabetic patients has been reported by many authors. In the present study, the extent of non-enzymatic glycosylation in diabetic patients with or without chronic complications was investigated. Eighty-five diabetic patients were studied, 20 were without any clinical evidence of chronic complications while the remainder were suffering from cataract (n = 18), retinopathy (n = 16), peripheral neuropathy (n = 16) and cardiovascular complications like angina pectoris, myocardial infarction and hypertension (n = 15). All patients were selected on clinical grounds. Fifteen apparently healthy subjects of similar age and weight were studied as control subjects. Fasting plasma glucose was increased in all diabetic patients and correlated significantly with glycosylated hemoglobin, glycosylated plasma protein and serum fructosamine concentrations. There was no significant difference between diabetic patients with or without chronic complications in the levels of fasting plasma glucose, glycosylated plasma proteins, glycosylated hemoglobin, serum fructosamine, mucoprotein, hexosamine, sialic acid and fucose. Alpha-2 globulin fraction was increased in both uncomplicated and complicated diabetic patients and albumin was found to be decreased in patients with cataract, peripheral neuropathy and cardiovascular diseases. Alpha-1 and beta globulins were significantly decreased in patients with cardiovascular diseases and retinopathy respectively while gamma globulin was increased in retinopathy patients. In uncomplicated diabetic patients alpha-1 glycoprotein was decreased and gamma glycoprotein was increased. In diabetic patients with retinopathy, alpha-1 glycoprotein was elevated significantly while beta glycoprotein was decreased.

Adult↗
PubMedDate not supplied

Prospective study of the enzymatic activities in urine of N-acetyl-beta-D-glucosaminidase, alpha-D-mannosidase, alpha- and beta-D-glucosidases, alpha-L- and beta-D-fucosidases, and beta-D-galactosidase in type I diabetes mellitus with early nephropathy.

Different surveys have been carried out on the plasma activities of different glycosidases in patients with insulin-dependent diabetes mellitus, but research on urinary glycosidases in this disease is scanty and incomplete. To elucidate the behavior of these lysosomal enzymes in the metabolic alterations occurring in the glomerular basal membrane during the initial stages of diabetic nephropathy, we conducted a prospective study to examine the urinary activities of N-acetyl-beta-D-glucosaminidase (NAG), alpha-D-mannosidase, alpha- and beta-D-glucosidase, alpha-L- and beta-D-fucosidase, and beta-D-galactosidase in patients with type I insulin-dependent diabetes mellitus, surveyed over 18 months, whose early diabetic nephropathy was detected by the presence of microalbuminuria. The simultaneous determination of beta 2-microglobulin in urine confirmed the glomerular origin of the albuminuria. No statistically significant correlation was found between the levels of albuminuria and the activities of any of the glycosidases analyzed. In the diabetic patients, a significant decrease was observed in the activities of all the enzymes (p < 0.05), except NAG and alpha-D-mannosidase, although the decrease in the latter was very close to statistical significance (p = 0.028, unilateral; p = 0.057 bilateral). Similarly, in the patients, there was a significant negative correlation (p < 0.05) with the serum levels of fructosamine, except with beta-D-galactosidase, which showed a positive correlation (p < 0.05) with fructosamine and blood HbA1c.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed2006

Catalytic amounts of fructose may improve glucose tolerance in subjects with uncontrolled non-insulin-dependent diabetes.

BACKGROUND: It was suggested that acute ingestion of small amounts of fructose can improve glucose homeostasis. AIM: To study the effect of a long-term tri-daily supplementation of catalytic amounts of fructose on glucose tolerance of subjects with type 2 diabetes (NIDDM). METHODS: A double-blind, placebo-controlled study. Twenty-six subjects with uncontrolled NIDDM as indicated by high levels of hemoglobin A1C (Hgb(A1c)) and 2-h postprandial glucose levels >200 mg% were assigned to either fructose or maltodextrin supplementation (7.5 g) tri-daily after each main meal. The subjects were challenged with a fixed meal and blood was drawn for determining levels of glucose, insulin and triglycerides before and 2 h after meal at baseline and 1 month after study entry. Blood was drawn for total cholesterol, high-density and low-density lipoprotein cholesterol (LDL-c), fructosamine and Hgb(A1C) before study entry and at 1, 2 and 3 months into the study. RESULTS: No changes were observed in the difference between postprandial and pre-meal glucose, insulin or triglyceride levels in each group or between groups. No significant statistical differences were found in weight, total cholesterol, LDL-c and high-density lipoprotein cholesterol (HDL-c) in each group or between groups along the study period. After 1 month fructosamin levels decreased in the fructose-supplemented group but not in the maltodextrin-supplemented group (P<0.052). Hgb(A1C) levels decreased with time in both groups but were significantly lower at 2 months in the fructose group as compared to the maltodextrin group (P<0.03). CONCLUSIONS: Subjects with NIDDM may benefit from daily supplementation of catalytic amounts of fructose in their diet.

Aged↗
PubMed2006

Danggui-Buxue-Tang decoction has an anti-inflammatory effect in diabetic atherosclerosis rat model.

Danggui-Buxue-Tang (DBT) is a famous traditional Chinese formula. We examined the anti-inflammatory effect of it in diabetic atherosclerosis rats. DBT (3 or 6g/kg/day for 4 weeks) was orally administrated to the diabetic atherosclerosis rats, which were induced by nitric oxide inhibition (l-NAME in drinking water, 1mg/ml) plus high-fat diet. The concentrations of circulating inflammatory markers C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-alpha) and serum fructosamine were determined. The results showed that DBT had no direct effect in lowering serum fructosamine level, but can decrease the concentrations of CRP and TNF-alpha, produce a higher survival rate and less body weight loss, and decrease water intake in diabetic atherosclerosis in GK rats.

Animals↗
PubMed2004

Identification of enzymes acting on alpha-glycated amino acids in Bacillus subtilis.

We have characterized the Bacillus subtilis homologs of fructoselysine 6-kinase and fructoselysine-6-phosphate deglycase, two enzymes that specifically metabolize the Amadori compound fructose-epsilon-lysine in Escherichia coli. The B. subtilis enzymes also catalyzed the phosphorylation of fructosamines to fructosamine 6-phosphates (YurL) and the conversion of the latter to glucose 6-phosphate and a free amino acid (YurP). However, their specificity was totally different from that of the E. coli enzymes, since they acted on fructoseglycine, fructosevaline (YurL) or their 6-phosphoderivatives (YurP) with more than 30-fold higher catalytic efficiencies than on fructose-alpha-lysine (6-phosphate). These enzymes are therefore involved in the metabolism of alpha-glycated amino acids.

Amino Acid Sequence↗
PubMedDate not supplied

Mosapride improves food intake, while not worsening glycemic control and obesity, in ob/ob obese mice with decreased gastric emptying.

Many patients with diabetes mellitus complain of early satiety and postprandial gastric fullness and discomfort. Mosapride citrate, a 5-HT4 receptor agonist, enhances gastric emptying and alleviates gastrointestinal discomfort in patients with diabetic gastroparesis. This study was undertaken to investigate the effects of mosapride citrate on feeding behavior in ob/ob obese mice with decreased gastric emptying. Mosapride citrate (1 mg/kg/day) was orally administered for 7 days. Food and water intake and body weight were measured daily. Blood glucose, serum insulin, and fructosamine concentrations were measured after 7 days of treatment. Orally administered mosapride citrate significantly increased food intake in ob/ob obese mice, with a tendency to decrease fasting blood glucose and fructosamine concentrations compared with controls. There were no significant changes in body weight after 7 days of treatment with oral mosapride citrate. These observations suggest that mosapride citrate may be useful in the treatment of appetite loss and improve the quality of life in patients with diabetes mellitus.

Administration, Oral↗
PubMed2004

Partial androgen deficiency in aging type 2 diabetic men and its relationship to glycemic control.

Aging in the male is associated with both a higher incidence of type 2 diabetes and hypogonadism. However, little information is available about the complex of symptoms and hormonal changes related to partial androgen deficiency in aging (called andropause) in type 2 diabetic men. Here, for the first time, we used a combination of clinical and hormonal criteria to define andropause and to analyze the relationships between the androgen environment and glucose metabolism in 55 type 2 diabetic men (63.6 +/- 7.9 years, mean +/- SD). Low plasma levels of total testosterone (< or =3.4 ng/mL) and free testosterone (< or =11 pg/mL) were found in 20% and 54.5%, respectively, of the diabetic men. The fraction of diabetic men with subnormal levels of total testosterone increased with aging: 14.2% (50 to 59 years), 17.4% (60 to 69 years) and 36% (> 70 years). The corresponding figures for subnormal values of free testosterone were 38%, 69.6%, and 54.5%, respectively. In the whole group of type 2 diabetic men, no significant linear correlations between total or free testosterone with fasting plasma glucose, insulin, C-peptide, or fructosamine values could be established. Total testosterone was positively correlated with glycosylated haemoglobin (HbA(1c)) levels (r =.322, P =.01). Although fasting plasma glucose was marginally higher in aging type 2 diabetic patients with andropause than in those without andropause (162 +/- 6.9 v 139 +/- 8.9, mean +/- SEM, P =.05), there were no differences between both subgroups for plasma fasting insulin, C-peptide, fructosamine, or HbA(1c) levels. Replacement therapy (150 mg intramuscular [IM] of enanthate of testosterone every 14 days for 6 months) was applied in 10 type 2 diabetic men with clinical features of andropause associated with subnormal concentrations of serum testosterone. The treatment induced significant increases in total plasma testosterone (baseline: 3.9 +/- 0.3; at 6 months: 7.1 +/- 0.9 ng/mL, mean +/- SEM, P =.003) and free testosterone (baseline: 9.3 +/- 0.6; at 6 months 17.6 +/- 2.4 pg/mL, P =.003), but had a neutral effect on overall glycemic control. These data show a high prevalence of andropause in aging type 2 diabetic men and suggest that the endogenous androgen environment, as well as correction of the partial androgen deficiency, do not have a meaningful effect on glycemic control.

Adult↗
PubMed2005

Effect of supplemental L-arginine on the function of T lymphocytes and the formation of advanced glycosylated end products in rats with streptozotocin-induced diabetes.

OBJECTIVE: We investigated the effect of supplemental L-arginine on lymphocyte function in diabetes and its association with suppressed formation of advanced glycosylated end products (AGEs). METHODS: For the in vivo study, rats with streptozotocin-induced (65 mg/kg of body weight, intravenously) diabetes were treated with or without 2% L-arginine or glycine (as a positive control) in drinking water for 8 wk. We then measured serum fructosamine concentrations and concanavalin A-induced proliferative ability of lymphocytes from these animals. For the in vitro study, AGEs derived from albumin were prepared by incubating D-glucose (200 mmol/L) and bovine serum albumin (100 mg/mL) at 37 degrees C for 2 wk in the presence or absence of L-arginine (0.1-10 mmol/L). These preparations were quantified for their bovine serum albumin--derived AGE content, and their effect on concanavalin A-induced proliferative activity of T lymphocyte from normal rats was measured. RESULTS: Serum fructosamine concentrations were significantly higher in the diabetic rats than in the control rats (P<0.05) but were significantly lowered with L-arginine supplementation (P<0.05). The lower lymphocyte proliferation rate found in the diabetic rats was reversed by supplemental L-arginine (P<0.05). During the course of incubation of bovine serum albumin with D-glucose, the presence of L-arginine prevented the formation of bovine serum albumin-derived AGEs and attenuated their inhibitory effect on the rate of lymphocyte proliferation in a dose-dependent manner. CONCLUSION: Supplemental L-arginine improved the function of T lymphocytes in diabetic rats in association with decreased formation of AGEs.

Animals↗
PubMed2001

A double-blind trial on the effects of atorvastatin on glycemic control in Japanese diabetic patients with hypercholesterolemia.

A double-blind, placebo-controlled, parallel-group study was performed to determine whether atorvastatin, a new HMG-CoA reductase inhibitor, could effectively and safely reduce plasma LDL-cholesterol concentrations in Japanese patients with type-2 diabetes without influencing glycemic control. The subjects were patients with hypercholesterolemia (serum cholesterol concentration > or =5.7 mmol/l (220 mg/dl)) and stable glycemic control. The fasting concentrations of hemoglobin A(1C) (HbA(1C)), fructosamine, and 1,5-anhydroglucitol (1,5-AG) were measured as indices of glycemic control. Plasma lipid concentrations and the safety of the drug were also examined. Forty eligible patients in two groups of 20 each were administered atorvastatin (10 mg/day) or placebo. Neither atorvastatin nor placebo caused a significant change in HbA(1C), fructosamine, or 1,5-AG concentrations. Atorvastatin significantly reduced total cholesterol and LDL-cholesterol concentrations from baseline by 29.7% (p<0.0001) and 41.6% (p<0.0001), respectively. The incidence of clinical adverse events and that of abnormal changes in laboratory test values did not differ between the two groups. In this trial, atorvastatin effectively and safely reduced LDL-cholesterol concentrations in diabetic patients with hypercholesterolemia without influencing glycemic control. These findings are clinically important because there are many diabetic patients with hypercholesterolemia and such patients have a high risk of developing arteriosclerotic disease.

Adult↗