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Biomedical subjects

K Tayama

Publications and source records attributed to K Tayama.

At least 19 recordsLinked to original sources

Enhancement of fibrinolysis in poorly controlled, hospitalized type 2 diabetic patients by short-term metabolic control: association with a decrease in plasminogen activator inhibitor 1.

Impaired fibrinolysis in type 2 diabetes may be caused by an increased plasma concentration of plasminogen activator inhibitor 1 (PAI-1), although the effects of short-term hypoglycemic therapy on fibrinolytic activity are poorly understood. This study investigated the effects of metabolic improvement on fibrinolysis activity and plasma concentrations of PAI-1 in poorly controlled, hospitalized type 2 diabetic patients. Forty-eight poorly controlled type 2 diabetic patients were studied; 26 were subsequently treated with sulfonylurea (SU) and 22 with insulin. The plasma concentrations of plasmin-alpha2-antiplasmin (PAP), a measure of fibrinolytic activity, plasma PAI-1, and fasting triglycerides and glucoses were measured at the beginning and the end of hospitalization. The body mass index and fasting triglyceride decreased significantly after treatment (p < 0.0001). The plasma concentration of PAP increased significantly (p < 0.01), and the plasma PAI-1 decreased by 50% after treatment. There was an inverse correlation between the changes in the plasma concentrations of PAP and PAI-1 (r= - 0.36, p = 0.023). Treatment with SU or insulin showed an increase in plasma PAP with a concomitant decrease in the plasma PAI-1 with equivalent glycemic control. In poorly controlled type 2 diabetic patients, the plasma PAP concentration can be significantly increased and the plasma PAI-1 antigen significantly reduced, even with short-term metabolic improvements including weight reduction, a better lipid profile, and tighter glycemic control with either SU or insulin therapy, and that enhanced fibrinolysis may be mediated partly through a decrease in the plasma PAI-1 after metabolic control.

Adult↗

Plasma interleukin-6 is associated with coagulation in poorly controlled patients with Type 2 diabetes.

AIMS: We investigated the relationship between interleukin (IL)-6 and coagulation, i.e. whether changes in the plasma IL-6 are associated with those in coagulation markers (D dimer and fibrinogen) after glycaemic control with sulphonylurea or insulin in poorly controlled patients with Type 2 diabetes. METHODS: We studied 42 patients with Type 2 diabetes, including 19 subsequently treated with sulphonylurea, 23 treated with insulin and 48 control subjects. All patients were in poor glycaemic control and were hospitalized for 3 weeks. At the beginning and end of treatment, we measured plasma concentrations of IL-6, fibrinogen, and D dimer. RESULTS: Plasma concentrations of IL-6 and D dimer were significantly higher in diabetic patients than in controls (P<0.0001 for both). In all patients with diabetes, the plasma concentration of IL-6 decreased significantly (P<0.001) after treatment. Changes in the plasma IL-6 during hospitalization were positively correlated with those in plasma D dimer and fibrinogen (r=0.664, P<0.0001; r=0.472, P=0.0042, respectively). Treatment with sulphonylurea or insulin caused a similar fall in the plasma IL-6 concentration with a concomitant decrease in the BMI and an equal improvement in glycaemia. CONCLUSIONS: In poorly controlled patients with Type 2 diabetes, plasma IL-6 concentrations were reduced significantly even by short-term metabolic control. As changes in the plasma concentrations of D dimer are related to plasma IL-6, plasma IL-6 may reflect a pro-coagulant as well as an inflammatory state in patients with Type 2 diabetes.

Blood Coagulation↗

The connection between QT dispersion and autonomic neuropathy in patients with type 2 diabetes.

It is controversial whether an increase in the QT dispersion (QTd) on the electrocardiogram (ECG) reflects cardiac autonomic neuropathy in diabetic patients. In the current study, the QTd was compared in 60 type 2 diabetic patients and in 30 healthy subjects, and its association with autonomic neuropathy in diabetic patients was investigated. An increased QTd was found in diabetic patients, compared to healthy subjects. The QTd had significant negative associations with the log of the low and high frequency power (log LF and HF, respectively) of the power spectral analyses (PSA) of heart rate variations and the systolic blood response during standing (Delta BP). There was no significant difference in the QTd between patients with and without sympathetic skin response (SSR), reflecting peripheral sympathetic function. A significant positive correlation was also found between QTd and the systolic blood pressure (SBP). On the other hand, there was no correlation between QTd and serum total cholesterol (TC), triglycerides (TG), fasting plasma glucose (FPG), hemoglobin (Hb) A (1C) concentrations or body mass index (BMI). By multiple regression analysis, the log HF, which reflects cardiac parasympathetic function, and the SBP alone were significantly associated with QTd as the dependent variable. The Delta BP and log LF, which partially reflect sympathetic nerve function, had no significant associations with QTd. These findings suggest that QTd reflects cardiac autonomic neuropathy (relative parasympathetic neuropathy) and that the QTd is also influenced by SBP, independent of autonomic neuro-function.

Adult↗

Primary antiphospholipid syndrome associated with acute adrenal failure.

We describe a 48-year-old woman with primary antiphospholipid syndrome who developed acute adrenal failure after an operation for a uterine myoma. After surgery, she developed a preshock state with hypotension, hypoglycemia, and hyponatremia. A diagnosis of primary antiphospholipid syndrome was made based not only on her past history of skin ulceration and recurrent spontaneous abortions but also on the presence of anticardiolipin antibodies. An abdominal computed tomography showed a bilateral enlargement of the adrenal glands but no high-density region in either gland. The patient recovered from the shock-like syndromes after the administration of glucocorticoids. Because it is possible that patients with antiphospholipid syndrome have acute or chronic adrenal failure caused by repeated hemorrhage or thrombosis, it may be important to monitor adrenal function in patients when the presence of this antibody is detected.

Acute Disease↗

Elevation of von Willebrand factor in plasma in diabetic patients with neuropathic foot ulceration.

AIMS: The present study examines the relationship between markers of endothelial dysfunction and diabetic neuropathy or consequent neuropathic foot ulceration in patients with Type 2 diabetes mellitus. METHODS: We studied 65 Type 2 diabetic patients including 25 diabetic patients without neuropathy, 27 with neuropathy but no history of foot ulceration, and 13 with neuropathic ulceration. Plasma concentrations of von Willebrand factor (vWF) and soluble thrombomodulin (TM), measures of endothelial dysfunction, were determined by enzyme immunoassays. We performed various tests quantifying aspects of diabetic neuropathy including vibration perception threshold (VPT; for sensory neuropathy), coefficient of variation of R-R intervals (CVR-R; for cardiac autonomic neuropathy), and cold-induced vasodilation in the great toe for peripheral sympathetic neuropathy. RESULTS: CVR-R and cold-induced vasodilation were significantly diminished in patients with neuropathic foot ulceration compared with patients with neuropathy but no history of foot ulceration. Plasma vWF concentrations were positively correlated with VPT and cold-induced vasodilation test, and were inversely correlated with CVR-R. Multivariate analysis disclosed that VPT and percentage vasodilation were independent factors for plasma vWF. Plasma vWF was significantly elevated in patients with foot ulceration compared with patients without neuropathy or those with neuropathy but not foot ulceration. However, plasma TM concentrations did not differ between the three groups. CONCLUSIONS: Diabetic patients with neuropathic foot ulceration had severe impairment of cardiac autonomic and peripheral sympathetic nerves. Elevation of vWF in plasma was associated with neuropathic foot ulceration, linking endothelial dysfunction to foot ulceration.

Autonomic Nervous System↗

The efficacy of acetic acid for glycogen repletion in rat skeletal muscle after exercise.

We examined the effect of acetic acid, the main component of vinegar, on glycogen repletion by using swimming-exercised rats. Rats were trained for 7 days by swimming. After an overnight fast, they were subjected to a 2-hr swimming exercise. Immediately afterward, they were given by gavage 2 ml of one of the following solutions: 30 % glucose only or 30 % glucose with 0.4 % acetic acid. Rats were sacrificed by decapitation before, immediately after exercise and 2 hours after the feeding. Exercise significantly decreased soleus and gastrocnemius glycogen content, and feeding significantly increased liver, soleus and gastrocnemius glycogen content. In soleus muscle, acetate feeding significantly increased glycogen content and the ratio of glycogen synthase in the I form (means +/- SEM: 4.04 +/- 0.41 mg/g-tissue and 47.0 +/- 0.7 %, respectively) in contrast to no acetate feeding (3.04 +/- 0.29 mg/g-tissue and 38.1 +/- 3.4 %, respectively). Thus, these findings suggest that the feeding of glucose with acetic acid can more speedily accelerate glycogen repletion in skeletal muscle than can glucose only.

Acetic Acid↗

[Long-term results of aortic root replacement for Marfan syndrome].

Between January 1974 and December 2000, aortic root replacement was performed for 46 patients with Marfan syndrome. The hospital mortality rate amounts to 8.6% (4 patients out of 46). Fifteen (35.7% of survivor) of 42 survivor died during the period of follow-up. Eighteen of 42 survivor were developed cardiovascular events of 21 times and 11 patients had to be reoperated on at least once for a total of 12 reoperations. Nine of 15 late death patient died in relation to aortic dissection and pseudoaneurysm of distal anastomosis and coronary anastomosis. Actuarial survival rate was satisfactory for 10 years after aortic root replacement, but sharply decreased after postoperative 10 years. The use of non-sealed graft, classical Bentall method, reoperation and inclusion technique were risk factors for the late death.

Adolescent↗

Goitrogenic effects of green tea extract catechins by dietary administration in rats.

The effects of green tea extract catechins on the rat thyroid were examined in a 13-week feeding study and subsequent 2-,4- and 8-week studies. Commercially available polyphenon-60 (P-60) which contains green tea extract catechins at 66.2% was used as a source of catechins. A basic diet containing different concentrations of P-60 was used for experiments. In the 13-week study, 10 rats of each sex were administered diets containing P-60 at 0 (control), 0.625, 1.25, 2.5 and 5.0%. Goiters were observed in the 13-week test. The mean thyroid weight of rats fed a diet containing 5.0% of P-60 (5.0% group) significantly increased to 444% of the control in males and to 304% of the control in females. Histological examinations of the thyroid of the 5.0% group revealed marked hypertrophy and/or hyperplasia of the follicles, some with depletion of colloid and some with rich colloid, and formation of a fibrous capsule. Slight hypertrophy of follicular cells was observed in male rats fed a diet containing 1.25% of P-60 (1.25% group) and female rats fed a diet containing 2.5% of P-60 (2.5% group). Degree and incidence of thyroid lesions were higher in males than in females in the 1.25, 2.5 and 5.0% groups. In the 2-8-week studies, five rats of each sex were given diets containing 0 (control) and 5.0% of P-60. In the 5.0% group, the mean thyroid weight in males significantly increased to 161% of the control as early as 2 weeks and increased to 357% of the control at 8 weeks. Histologically, these goiters were also associated with follicular cell hypertrophy/hyperplasia as in the 13-week study. The degree and incidence of thyroid lesions were higher in males than in females. These results indicate that dietary administration of the green tea extract catechins at high doses induced goiters in rats, and this may be due to antithyroid effects of catechins. In the 13-week study, the no-observed effect level (NOEL) of green tea extract catechins for F344 rats based on histological changes of the thyroid was considered to be 0.625% in males and 1.25% in females in the diet, respectively.

Administration, Oral↗

Estrogenic potency of benzophenone and its metabolites in juvenile female rats.

The estrogenic activity of benzophenone and its metabolites, benzhydrol and p-hydroxybenzophenone, were investigated in vitro by estrogen receptor (ER) competitive ligand binding assay and in vivo by uterotrophic assay in juvenile female Sprague-Dawley (SD) rats. p-Hydroxybenzophenone as well as diethylstilbestrol and bisphenol A, known xeno-estrogenic compounds, competed with fluorescein-labeled 17 beta-estradiol to bind human recombinant ER alpha in a concentration-dependent manner. Fifty percent inhibitory values (IC50) of diethylstilbestrol, bisphenol A, and p-hydroxybenzophenone were approximately 10(-8), 10(-5), and 5 x 10(-5) M, respectively. However, neither the parent compound nor benzhydrol at concentrations from 10(-9) to 5 x 10(-4) M impaired the binding of 17 beta-estradiol to ER alpha. Juvenile female rats (21-days-old) were given s.c. injections of benzophenone, its metabolites, and 17 beta-estradiol for 3 days. Administration of p-hydroxybenzophenone (100-400 mg/kg) elicited an increase in absolute and relative uterine weights in a dose-dependent manner and 17 beta-estradiol (10 micrograms/kg) increased uterine weight approximately fourfold relative to control. The uterine response caused by both compounds was accompanied by an increase in luminal epithelial height and stromal cells in the uterus and an increase in thickness of vaginal epithelial cell layers with cornification. In contrast, benzophenone and benzhydrol at a dose of 400 mg/kg affected neither uterine weight nor histological changes of the uterus and vagina. These results indicate that p-hydroxybenzophenone, a metabolite of benzophenone, exhibits intrinsic xeno-estrogenic activity in the female reproductive tract.

Animals↗

Toxicity and effects of 2,6-di-tert-butyl-4-methylphenyl N-methylcarbamate (terbutol) on hepatic cytochrome P450 in F344 rats.

The subacute toxicity and effects of 2,6-di-tert-butyl-4-methylphenyl N-methylcarbamate (terbutol) on hepatic microsomal cytochrome P450 (P450) were investigated in male and female F344 rats. Rats were given 0.25, 0.5, and 1.0% terbutol for 28 days. Liver weights of male and female rats increased at all dose levels. The compound did not affect activity or amount of serum biochemical markers related to hepatic damage. The concentrations of terbutol in rat serum were less than 0.1 microM, and its major metabolites in serum were 2,6-di-tert-butyl-4-carboxyphenyl N-methyl-carbamate and 2,6-di-tert-butyl-4-carboxyphenol. In male rats, P450 and cytochrome b5 (b5) contents, and NADPH cytochrome c reductase (fp2) activity in liver microsomes were increased about 2-fold by 1% terbutol administration for 7 to 28 days. Among the P450-dependent monooxygenase activities in liver microsomes, 7-benzyloxyresorufin-O-debenzylase (BROD) activity was greatly increased by 100-fold, and 7-ethoxyresorufin-O-deethylase (EROD), 7-ethoxycoumarin-O-deethylase (ECOD), and aminopyrine-N-demethylase (APND) activities were elevated 2- to 3-fold. 7-Methoxyresorufin-O-deethylase (MROD), erythromycin-N-demethylase (EMND), estradiol 2-hydroxylase (ED2H), chlorzoxazone 6-hydroxylase (CZ6H), and lauric acid omega-hydroxylase (LAOH) activities were unchanged. For the activities of testosterone hydroxylation, testosterone 16beta-hydroxylase (T16BH) activity was markedly increased by 30-fold, and testosterone 6beta-hydroxylase (T6BH) and testosterone 7alpha-hydroxylase (T7AH) activities were slightly elevated. Testosterone 2alpha-hydroxylase (T2AH) activity was not affected. Terbutol 4-methylhydroxylase (T4MH) activity was increased 9-fold by 1% terbutol. In an immunoinhibition study, T4MH activity in liver microsomes from 1% terbutol-treated rats was decreased about 50% by polyclonal anti-rat CYP2B1, whereas polyclonal anti-rat CYP2A1 and CYP2C11 did not affected the activity. These results indicate that terbutol increased CYP2B subfamily in rat liver microsomes, and that the compound did not cause serious hepatic damage.

Administration, Oral↗

Surgical management of a graftenteric fistula: a modified method of in situ reconstruction.

Between December 1989 and May 1998, we performed a modified method of in situ reconstruction on three of seven patients with graftenteric fistulas (GEFs) at the Kurume University Hospital. The modification involved performing an anastomosis of the infrarenal abdominal aorta and running a new prosthesis through the left side of the descending colon in the retroperitoneal cavity, and wrapping the proximal anastomosis and the proximal site of the prosthesis in the greater omentum. Good results were achieved in all three patients. We describe herein this modified method of in situ reconstruction for a GEF and summarize the case reports of these three patients.

Adult↗

High-dose cimetidine reduces proinflammatory reaction after cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Cimetidine, which is usually used for gastric ulcer, enhances cellular immunity. The effect of cimetidine on perioperative proinflammatory response after cardiac surgery with cardiopulmonary bypass was investigated. METHODS: Elective coronary artery bypass graft cases in which CPB was performed were placed randomly in a cimetidine (C) group (n = 20) or a no-treatment (N) group (n = 20). The time course of plasma levels of neutrophil elastase, interleukin (IL)-6 and IL-8, leukocyte counts, lymphocyte recovery ratio, C-reactive protein, creatine-kinase-MB, and oxygenation index were analyzed. RESULTS: The plasma levels of neutrophil elastase and IL-8 were inhibited in the C groups at 2 hours after CPB termination. In a comparison of the two groups, the C group demonstrated higher lymphocyte recovery ratio and lower C-reactive protein on postoperative day 5 and shorter intubation time. No intergroup differences were observed in IL-6, leukocyte counts, creatine-kinase-MB levels, or oxygenation index. CONCLUSIONS: Cimetidine may reduce surgical stress and augment the immune system after cardiac surgery with cardiopulmonary bypass.

Aged↗

Effect of acetate on glycogen replenishment in liver and skeletal muscles after exhaustive swimming in rats.

Immediately after exhaustive swimming, rats were given one of the following orally: distilled water (W), glucose (G); acetic acid (A); citric acid (C); glucose and acetic acid (GA); and glucose and citric acid (GC), and they were killed 2 h after ingestion (each trial: n=4). Exhaustive exercise resulted in a significant reduction of the glycogen store in the gastrocnemius muscle. The glycogen stores in the liver were significantly higher following ingestion in groups GA and GC, in the gastrocnemius in groups G, GA and GC, and in the soleus in group GC, than immediately post exercise. These results suggest that oral acetic acid with glucose can facilitate liver glycogen restoration during the early period of recovery, and that acetate has about the same physiological effects as citrate on glycogen replenishment.

Acetic Acid↗

Changes in skin blood flow in type 2 diabetes induced by prostacyclin: association with ankle brachial index and plasma thrombomodulin levels.

In a previous study, we reported that beraprost sodium (BPS), a stable prostaglandin I(2) (PGI(2)) analog, increases skin blood flow in the feet of both control subjects and patients with type 2 diabetes, and that the flow increase induced by BPS is lower in diabetic patients than in controls. The present study was undertaken to clarify factors associated with smaller increases in skin blood flow in the feet of patients with type 2 diabetes after the administration of BPS, and to investigate the relationship between microalbuminuria and the changes in skin blood flow induced by the PGI(2) analog. We studied 61 patients with type 2 diabetes: 10 received placebo (control) and 51 (31 with normoalbuminuria and 20 with microalbuminuria) received BPS. Using laser Doppler flowmetry, we measured the skin blood flow at the pulp of the right big toe before and 90 minutes after administration of 40 microg BPS, and calculated the change in blood flow, i.e., delta flux (peak flux at 90 minutes - basal flux at 0 minutes). Plasma concentrations of soluble thrombomodulin (TM) were determined using an enzyme immunoassay (EIA) sandwich method. BPS significantly increased skin blood flow in the treatment group compared with the placebo group (P <.01). The delta flux was positively correlated with the value of the ankle brachial index (ABI) (r =.41, P <.0038) and was negatively correlated with plasma TM levels (r = -.53, P <.0001). By multiple regression analysis both the ABI value and the plasma TM level retained a significant influence on delta flux. Furthermore, both the delta flux and the ABI value in patients with microalbuminuria were lower than in patients with normoalbuminuria (P <.05). The results suggest that BPS increases the skin blood flow of the toe of patients with type 2 diabetes and that the increased flow is independently influenced by the value of the ABI and the plasma TM levels; in addition, microalbuminuria is associated with the impairment of vasodilation in the feet in response to BPS.

Adult↗

Relationship between plasma soluble thrombomodulin levels and insulin resistance syndrome in type 2 diabetes: a comparison with von Willebrand factor.

Endothelial dysfunction plays a pivotal role in the initial stage of atherosclerosis. Insulin resistance is associated with accelerated atherosclerosis, especially coronary heart disease. To elucidate the relationship between endothelial dysfunction and insulin resistance or insulin resistance syndrome in patients with type 2 diabetes, we investigated the correlation between plasma soluble thrombomodulin (TM) and von Willebrand factor (vWF), measures of endothelial dysfunction, and the degree of insulin resistance evaluated by homeostasis assessment models of insulin resistance (HOMA-IR), or variables of insulin resistance syndrome. We studied 53 patients with type 2 diabetes, 23 treated with diet alone and 30 treated with sulfonylureas, who had normal renal function. The plasma soluble TM concentrations were highly correlated with HOMA-IR (r=0.64, p<0.0001), the plasma insulin (r=0.72, p<0.0001), the systolic blood pressure (r=0.45, p=0.0005), and the plasma fibrinogen (r=0.43, p=0.0018), while they were inversely correlated with the serum HDL cholesterol concentrations (r=-0.27, p=0.0344). The plasma vWF concentrations were positively correlated with HOMA-IR (r=0.35, p=0.0151) and the plasma fibrinogen (r=0.32, p=0.0203), but not with the plasma insulin, the systolic blood pressure or the HDL cholesterol concentrations. Furthermore, plasma TM, but not vWF, was positively correlated with total number of variables of insulin resistance syndrome (r=0.45, p=0.0005). These results indicate that endothelial dysfunction may be associated with the pathogenesis of insulin resistance syndrome as well as insulin resistance, and that the plasma TM might reflect endothelial damage better than the plasma vWF in the state of insulin resistance in patients with type 2 diabetes.

Adult↗

Clinical features of a polymorphism of the beta3-adrenergic receptor gene in patients with type 2 diabetes mellitus--a study using a pin-point sequencing method.

UNLABELLED: The human beta(3)-adrenergic receptor (beta(3)AR) is expressed specifically in adipose tissues, and its activation is activated in brown adipose tissues during thermogenesis and in white adipose tissues during lipolysis. We investigated the relationship between a polymorphism of the beta(3)AR gene and the clinical features of type 2 diabetes mellitus. Studies were conducted in 30 type 2 diabetic patients (15 males and 15 females). Analysis of polymorphisms of the beta(3)AR gene was performed by a pin-point sequencing method using the hair of the subjects. Preperitoneal (P-fat) and subcutaneous fat (S-fat) levels were determined by ultrasonography. We found a Trp(64)Arg allele of the beta(3)AR gene in the hair of 27% of all patients. The patients with this mutation showed a significantly younger onset-age of diabetes than those of the wild type. The body mass index, serum GPT levels, fasting immunoreactive insulin (IRI) and daily urinary C-peptide reaction (CPR) in the mutation group were markedly higher than in the wild type group. The P-fat, serum cholesterol and leptin concentrations tended to be higher in the mutation group. Patients in the mutation group had a significantly higher prevalence of hypertension (80%) compared with those in the wild type group (20%). CONCLUSIONS: The present results suggest that the clinical features of diabetic patients with a missense mutation in the beta(3)AR gene are substantially distinct from those of the wild type patients. These specific features include obesity, hyperinsulinemia, hypertension, and an increase in preperitoneal fat.

Adipose Tissue↗

Acetic acid feeding enhances glycogen repletion in liver and skeletal muscle of rats.

To investigate the efficacy of the ingestion of vinegar in aiding recovery from fatigue, we examined the effect of dietary acetic acid, the main component of vinegar, on glycogen repletion in rats. Rats were allowed access to a commercial diet twice daily for 6 d. After 15 h of food deprivation, they were either killed immediately or given 2 g of a diet containing 0 (control), 0.1, 0.2 or 0.4 g acetic acid/100 g diet for 2 h. The 0.2 g acetic acid group had significantly greater liver and gastrocnemius muscle glycogen concentration than the control group (P < 0.05). The concentrations of citrate in this group in both the liver and skeletal muscles were >1.3-fold greater than in the control group (P > 0.1). In liver, the concentration of xylulose-5-phosphate in the control group was significantly higher than in the 0.2 and 0.4 g acetic acid groups (P < 0.01). In gastrocnemius muscle, the concentration of glucose-6-phosphate in the control group was significantly lower and the ratio of fructose-1,6-bisphosphate/fructose-6-phosphate was significantly higher than in the 0.2 g acetic acid group (P < 0.05). This ratio in the soleus muscle of the acetic acid fed groups was <0.8-fold that of the control group (P > 0.1). In liver, acetic acid may activate gluconeogenesis and inactivate glycolysis through inactivation of fructose-2,6-bisphosphate synthesis due to suppression of xylulose-5-phosphate accumulation. In skeletal muscle, acetic acid may inhibit glycolysis by suppression of phosphofructokinase-1 activity. We conclude that a diet containing acetic acid may enhance glycogen repletion in liver and skeletal muscle.

Acetic Acid↗