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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 973 records · Page 54Linked to original sources

[Effects of nizatidine, a new histamine H2-receptor antagonist, on gastric acid secretion and various gastric and duodenal lesions in rats: comparison with cimetidine].

We examined the antisecretory and antilesion activities of nizatidine in rats. Male SD or Donryu rats (200-260 g) were used under fasted or fed conditions. Nizatidine, given orally or parenterally (intraperitoneally, subcutaneously or intraduodenally) at 0.3-150 mg/kg, inhibited both basal (pylorus-ligation preparations) and histamine-stimulated gastric acid secretion (acute fistula preparations) in a dose-dependent manner. The potency of nizatidine was 2 to 8 times greater than cimetidine when the ED50 values (mg/kg or mu mole/kg) of each agent were compared. The antisecretory activity of nizatidine, given orally, persisted for more than 3.5 hr, but disappeared 6 hr later. Nizatidine, given orally or subcutaneously at 0.3-150 mg/kg, prevented development of gastric lesions induced by water immersion, pylorus ligation (Shay), histamine, aspirin, or indomethacin in a dose-dependent manner. Duodenal ulcers induced by mepirizole were also markedly prevented with nizatidine. The potency of nizatidine on stress lesions or duodenal ulcers was about 20 or 14 times greater than that of cimetidine, respectively. Nizatidine, given orally 3 times a day for 4 weeks, significantly (P less than 0.05) accelerated the healing of acetic acid-induced gastric ulcers which were delayed by prolonged treatment with indomethacin. These results suggest that nizatidine is a useful drug for the treatment of peptic ulcers in man.

Animals↗

A continuous monitoring of mucosal integrity and secretory activity in rat stomach: a preparation using a lucite chamber.

We assembled a new system using a lucite chamber and rat stomach for simultaneous measurement of transmucosal potential difference (PD) and luminal pH as indicators of the mucosal integrity and the secretory activity, respectively. The biological preparation involved only the glandular mucosa and responded to a variety of mucosal damaging agents by different degrees of PD reduction, pH increases and histological damages. When the mucosa was exposed for 10 min to 1 M NaCl, the reduced PD was restored with time, reaching the baseline values within 2 hr with histological restitution. Titration of gastric effluent showed that after the exposure, acid secretion ceased and a considerable amount of HCO3- was evident in the lumen, followed by re-secretion of acid. These secretory changes corresponded with those of luminal pH; this remained elevated for 1 hr after the exposure and returned to the basal values 2 hr later. The histological restitution as well as the PD recovery after damage were significantly interfered with by indomethacin (5 mg/kg, s.c.) or vasopressin (10 unit/kg/hr, i.v.), respectively, at the dose which inhibited the increased pH responses caused by 1 M NaCl or reduced the mucosal blood flow. These results suggest that this system may be useful for studying physiological changes of gastric mucosa after acute injury and for screening drugs that may have an effect on the repair process.

Animals↗

Mechanisms involved in aggravation of ethanol-induced gastric mucosal lesions in adrenalectomized rats.

Effects of adrenalectomy (AD) on ethanol-induced gastric injury and prostaglandin (PG) protection on the damage were investigated in rats and compared with those of N-ethylmaleimide (NEM), a sulfhydryl (SH) blocker, and diethyl maleate (DEM), a SH depletor. Oral administration of 100% ethanol (1 ml) induced elongated bands of hemorrhagic lesions in the corpus mucosa of sham operated rats, and these lesions were significantly prevented by 16,16-dimethyl PGE2 (dmPGE2, 10 micrograms/kg, s.c.). AD markedly enhanced the mucosal ulcerogenic responses caused by ethanol and abolished the protective effect of dmPGE2; this agent rather worsened the lesions, which appeared throughout the corpus mucosa. AD by itself enhanced the microvascular permeability in the gastric mucosa without any effect on SH contents. These alterations caused by AD were significantly reverted by hydrocortisone treatment (10 mg/kg/day for 2 weeks, s.c.). On the other hand, a single injection of NEM (10 mg/kg, s.c.) similarly enhanced the vascular permeability, worsened the ethanol-induced lesion, and mitigated the protective effect of dmPGE2 without altering mucosal SH contents, while DEM (1 ml/kg, s.c.) significantly reduced the mucosal SH levels and the lesions. These results suggest that AD worsened the mucosal lesions induced by ethanol, probably by enhancing the microvascular permeability, and this action may be due to a lack of steroid secretion but is not directly related to a mucosal SH deficiency.

16,16-Dimethylprostaglandin E2↗

Histamine-induced villous damage in the rat duodenum.

A single s.c. administration of histamine dose-dependently (5-20 mg/kg) induced villous damage of the proximal duodenum in 24-hr fasting rats. Time course studies indicate that histamine (20 mg/kg) induced severe exfoliation of the epithelial cells at the villous tips of the duodenal mucosa 0.5 hr after administration. The damage, however, tended to heal with time, and recovery was nearly complete 8 hr later. This villous damage was significantly inhibited by pretreatment with sodium bicarbonate given orally or cimetidine, omeprazole and NC-1300 given subcutaneously. Histamine (20 mg/kg) significantly stimulated gastric acid secretion and lowered the intraduodenal pH for 1 hr. Gastric content was significantly greater than that in the control group for 1 hr after histamine administration, probably due to stimulated gastric secretion and delayed emptying. We conclude that a single administration of histamine induces microscopical duodenal damage by stimulation of gastric acid secretion, but the damage heals with time, probably as a result of the short periods of acid stimulation and delayed emptying.

Animals↗

The relationship of intraduodenal pH and delayed gastric emptying in duodenal ulceration induced by mepirizole or cysteamine in rats.

Subcutaneous administration of mepirizole (60 and 200 mg/kg) and cysteamine (100 and 300 mg/kg) to fasted rats consistently induced localized villous damage to the proximal duodenum after 6 to 8 hr. The severity of the damage in animals treated with the low doses remained unchanged at 12 hr. With the high doses, however, well-defined deep ulcers were evident by that time, the incidence being high. The agents caused a significant accumulation of highly acidic gastric contents for 6 to 8 hr, but the accumulated gastric contents had markedly decreased by 12 hr. The intraduodenal pH in these animals was significantly lowered for 8 hr with the low doses, but for 12 hr with the high doses. Both mepirizole and cysteamine significantly delayed gastric emptying which was quantitated by weighing the food residue in refed animals. This delay in emptying was observed for 6 to 8 hr with the low doses and for 12 hr with the high doses. We conclude that this prolonged accumulation of gastric contents for up to 8 hr, resulting in a continuous lowering of the intraduodenal pH for 12 hr, is a crucial factor for the progression from duodenal villous damage to visible ulcers in response to mepirizole and cysteamine.

Animals↗

Pathogenesis of the earliest epithelial cell damage induced by mepirizole and cysteamine in the rat duodenum.

Mepirizole (200 mg/kg) and cysteamine (100 mg/kg) induced epithelial cell damage in the proximal duodenum of rats within 30 min after s.c. administration. The injury induced was severe 60 min later. Gastric acid secretion determined in intact animals was stimulated by these agents 30 and 60 min later when the intraluminal pH of the duodenum was significantly decreased. Duodenal blood flow was significantly decreased beginning 5 min after administration up to 60 min. Oral treatment with sodium bicarbonate (300 mg/kg), cimetidine (100 mg/kg), omeprazole or NC-1300 (gastric proton pump inhibitors, 30 mg/kg) and 16,16-dimethyl prostaglandin E2 (10 micrograms/kg) protected the epithelium from damage induced by the two duodenal ulcerogens. Epithelial cell damage in the duodenum in response to mepirizole and cysteamine appears to be related to the increased gastric acid secretion followed by lowered intraduodenal pH of the duodenum having decreased blood flow.

Animals↗

[Effects of noise on sleep. Part 1. Development of an automatic analysing system for all-night sleep polygraphy by microcomputer].

In order to assess the effects of noise on sleep, the authors have developed a microcomputer system which determines the sleep stage based on an all-night EEG (electroencephalogram), rapid eye movement and an EMG (electromyogram). All the polygraphic parameters for each epoch (including spindle, rapid eye movement, alpha and delta waves, and amount of muscle tension), which are necessary to determine the sleep stage, were determined by a microcomputer using a digital data processing program. Recognition of EEG waves is based on Fujimori's method with some modifications. The rules of Rechtschaffen et al. were adopted for judging sleep stage with a slight modification. Data were obtained from six healthy students of a university. Each student was polygraphed for five to six nights under various conditions of noise exposure. Judgements of the sleep stage were made by two medical doctors. Using randomly selected 10 nights' data, the agreement between judgements by the microcomputer system and by the doctor was 77%. The percentage of agreement increased to 84% for the epochs in which the two doctors agreed. It takes about one hour to determine all-night sleep stages by this system.

Adult↗

[Baseline study of sleep electroencephalography--daily variation and individual variation].

The aims of the present study were to observe the daily habituation to night sleep in a laboratory environment and to make clear the daily and individual sleep variations by using polygraph parameters, including electroencephalography (EEG). Sleep EEG records were obtained from a subject who slept ten successive nights, and from six subjects who each slept one night in the laboratory. The parameters used were as follows: sleep stage %, sleep latency (SL), REM latency (RL), number of stage shifts, subjective sleep, integral EMG, and slope (a) and intersect (b) of a regression equation used to estimate the sleep depth against sleep time. Stage WAKE and SL, slope (a), intersect (b) and the mean depth of sleep were found to become stable from the fifth night. Stage MT, the number of stage shifts, and integral EMG increased significantly from the fifth night and later, showing p less than 0.01, p less than 0.01, and p less than 0.05, respectively. Judging from these findings, the sleep habituation of the subject in the laboratory was completed within the first four nights. Coefficients of variation of sleep stage 2 and stage REM of the ten-nights' EEG were the lowest among all the sleep parameters examined. Almost all the parameters of day-to-day sleep of the subject who slept for ten successive nights in the laboratory showed smaller variations than those of the other six subjects. It may be concluded that the mist effect on sleep could be assessed more precisely by using an individual repeatedly than by using a group of subjects.

Adult↗

Plasma aldosterone level in a female case of pseudohyperaldosteronism (Liddle's syndrome).

A 22-yr-old female suffering from hypertension, hypokalemic alkalosis and suppressed plasma renin activity was studied. The plasma aldosterone concentration (PAC) ranged between subnormal and normal levels while the other adrenal mineralocorticoids were normal. Examinations through computed tomography and ultrasonography showed no abnormal findings. For differential diagnosis, dexamethasone, spironolactone and triamterene were administered. Triamterene alone corrected the abnormalities in this case, and the therapeutic effect was further enhanced by sodium restriction. Therefore, the present case is strongly suggested to be one of Liddle's syndrome, which is characterized by a primary defect in renal tubular sodium handling and can be corrected with triamterene. However, the patient in our study is different from the first reported case in which aldosterone secretion was estimated to be low. Analysis of the changes in PAC has shown that PAC is parallel with the level of plasma progesterone in accordance with the rhythm of the menstrual cycle and, in the follicular phase, PAC is rather low. It is concluded that the patient was suffering from Liddle's syndrome, and it is assumed that PAC is not always subnormal and, as same as in normal females, PAC may change in accordance with the rhythm of the menstrual cycle in a female case of Liddle's syndrome.

Adult↗

Acute and chronic effects of synthetic atrial natriuretic factor on blood pressure and sodium excretion in spontaneously hypertensive rats.

To assess possible roles of atrial natriuretic factor (ANF) in the regulation of blood pressure in spontaneously hypertensive rats (SHR), we performed two series of experiments. First, we studied acute hypotensive, natriuretic and diuretic effects of ANF in pentobarbital-anesthetized SHR and age-matched Wistar-Kyoto rats (WKY). A synthetic ANF of 25 amino acid residues was intravenously administered as a bolus at doses of 0.1, 1.0, 2.5 and 5.0 micrograms/kg. In SHR group, a significant decrease in mean arterial pressure (MAP) was observed at a dose of 1.0 micrograms/kg, and the decrease was dose-dependent. On the other hand, in WKY group, the hypotensive effect of ANF was not observed until a dose of 5.0 micrograms/kg. The diuretic and natriuretic effects of ANF were observed at a dose of 2.5 micrograms/kg in SHR and 5.0 micrograms/kg in WKY, respectively. Second, we also studied chronic effect of ANF on the development of hypertension in 6-week-old SHR. The SHRs, on regular diet or given 1% NaCl solution for drinking, were continuously infused into the jugular vein by osmotic minipumps with ANF (15, 75 and 150 micrograms/kg/day) or vehicle (physiological saline) as controls for up to 14 days. ANF at a dose of 150 micrograms/kg/day attenuated transiently the development of hypertension in the sodium-loaded SHR. However, the blood pressure returned to control levels by day 5. ANF at doses of 15 and 75 micrograms/kg/day did not affect the development of hypertension. In SHR on regular diet, ANF at a dose of 150 micrograms/kg/day did not affect the development of hypertension. In addition, ANF did not induce any significant changes in urine volume, fluid intake, and urinary excretion of sodium and potassium in SHR, whether they were sodium-loaded or not, when compared to those in vehicle-infused SHR. These results indicate that there may be a significant difference in the sensitivity to diuretic, natriuretic and hypotensive actions of ANF between SHR and WKY. Moreover, it is suggested that ANF may play significant roles by its vascular effect at the early stage of development of hypertension in sodium-loaded SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Blood pressure and renal responses to synthetic rat atrial natriuretic factor in deoxycorticosterone acetate-salt hypertension.

To assess possible roles of atrial natriuretic factor (ANF) in the regulation of blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, we performed two series of experiments. First, we studied acute hypotensive, and natriuretic and diuretic effects of ANF in pentobarbital-anesthetized DOCA-salt hypertensive rats and age-matched controls. A synthetic rat ANF was intravenously administered as a bolus at doses of 0.5, 2.5 and 5.0 micrograms/kg. In DOCA-salt rats, a significant decrease in mean arterial pressure was observed at a dose of 5.0 micrograms/kg, whereas at a dose of 2.5 micrograms/kg in control rats. On the other hand, the diuretic and natriuretic effects of ANF were observed at a dose of 2.5 micrograms/kg in DOCA-salt rats and 5.0 micrograms/kg in control rats. Second, we examined chronic effect of ANF on the development of hypertension in DOCA-salt rats. The DOCA-salt rats, given 1% NaCl solution for drinking, were continuously infused with ANF (15, 75 and 150 micrograms/kg/day) or vehicle (physiological saline) into the jugular vein by osmotic minipumps for up to 14 days. In DOCA-salt treated rats, ANF at doses of 75 and 150 micrograms/kg/day attenuated significantly the development of hypertension, although at a dose of 15 micrograms/kg/day did not. The hypotensive effect of ANF was sustained throughout the experimental period and the effect of ANF at a dose of 150 micrograms/kg/day was more prominent than that of this peptide at a dose of 75 micrograms/kg/day. ANF did not induce any significant changes in urine volume, fluid intake and urinary excretion of sodium and potassium in DOCA-salt rats when compared to those in vehicle-infused DOCA-salt rats. These results indicate that DOCA-salt rats are more sensitive to ANF in diuretic and natriuretic effects, and less sensitive to ANF in hypotensive effect compared to control rats. Moreover, it is suggested that ANF can affect the regulation of blood pressure by its vascular effect in the development of hypertension in DOCA-salt rats.

Animals↗

Comparison of immunoreactive renin and plasma renin activity in human plasma.

Measurement of immunoreactive plasma renin concentration (PRC) using direct radioimmunoassay (RIA) was compared with the common procedure, measurement of plasma renin activity (PRA). The sensitivity of the PRC assay was 5 pg/ml. In 67 normal subjects aged 45.2 +/- 1.2 year, the mean PRC value was 17.0 +/- 0.9 pg/ml in the recumbent position and 38.0 +/- 5.4 pg/ml in the upright position. In patients with high renin essential hypertension and renovascular hypertension, discrepancies were observed between changes in PRA and PRC at 60 min after the administration of captopril. In a patient with Bartter's syndrome PRC was markedly elevated (393 pg/ml) and the changes in PRA and in PRC after captopril were very different (452% vs. 1249%). In all 10 cases of primary hyperaldosteronism PRC was less than 5 pg/ml. The correlation coefficient between PRC and PRA was 0.85 (n = 227, p less than 0.01). The slope of the regression line between PRA and PRC decreased in proportion to PRC values. Direct RIA for PRC is likely to be useful for the determination of plasma active renin when renin levels are high or substrate concentrations are abnormal. Moreover, the combined use of PRA and PRC measurements might be useful in assessing abnormalities in renin substrate concentration as well as in PRC.

Adolescent↗

The effect of atrial natriuretic peptide on cytosolic free calcium in cultured vascular smooth muscle cells.

Effect of atrial natriuretic peptide (ANP) on cytosolic free calcium [( Ca2+]i) was studied in monolayers of cultured vascular smooth muscle (VSM) cells loaded with a fluorescent calcium indicator, fura-2. Vasoconstrictive hormones, angiotensin II (AII) and Arg8-vasopressin (AVP) induced initial rapid rises in [Ca2+]i, followed by sustained elevation of [Ca2+]i. ANP (Atriopeptin III 10(-8) M) decreased both the resting level and the sustained elevation of [Ca2+] i induced by AII and AVP. ANP also decreased the rise in [Ca2+]i induced by high potassium (K+) depolarization. AVP-induced initial rapid rise in [Ca2+]i was not inhibited by ANP in the presence or absence of the phosphodiesterase inhibitor, isobutylmethylxanthine 0.1 mM, which has been shown to fully enhance ANP-induced cyclic GMP accumulation. On the other hand, a calcium antagonist, nicardipine, inhibited the high K+-induced rise in [Ca2+]i, whereas it had no effect on not only initial but also sustained rises in [Ca2+]i induced by AVP or AII. These results suggest that ANP has an ability to decrease [Ca2+]i not through inhibition of voltage-sensitive calcium channels, and that neither ANP nor ANP-induced cyclic GMP may affect initial hormone-induced rise in [Ca2+]i. In conclusion, an ability to decrease [Ca2+]i is implicated in ANP-induced relaxation of VSM.

1-Methyl-3-isobutylxanthine↗

Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation.

To determine whether pharmacological control of blood pressure could affect the renal function and levels of atrial natriuretic polypeptide (ANP) in spontaneously hypertensive rats (SHR) with renal ablation, and to ascertain the benefits of antihypertensive drugs, we studied effects of oral administration of captopril (50 mg/kg/day), an inhibitor of angiotensin converting enzyme, benidipine (3 mg/kg/day) and nilvadipine (10 mg/kg/day), newly developed blockers of calcium channel, and indapamide (10 mg/kg/day) for 14 days on systolic blood pressure, serum creatinine, blood urea nitrogen, and plasma ANP concentration in SHR subjected to surgical removal of the left kidney and infarction of two-thirds of the right kidney (5/6 nephrectomy) a week before. Three weeks after the surgery, systolic blood pressure (mmHg) in the untreated group was 253 +/- 9 (n = 10), in the captopril group 156 +/- 9 (n = 7, p less than 0.05), in the benidipine group 197 +/- 9 (n = 7, p less than 0.05), in the nilvadipine group 146 +/- 9 (n = 7, p less than 0.05) and in the indapamide group 206 +/- 5 (n = 7, p less than 0.05). Serum creatinine (mg/100 ml) was lower in the captopril group (0.58 +/- 0.02, n = 7, p less than 0.05) and in the benidipine group (0.50 +/- 0.03, n = 7, p less than 0.05) but not in the nilvadipine group and in the indapamide group 3 weeks after 5/6 nephrectomy compared to the untreated group. Blood urea nitrogen was also lower in the captopril group and in the benidipine group but not in the nilvadipine group and in the indapamide group. Plasma ANP concentration was significantly reduced by the treatment with captopril and benidipine but not with nilvadipine and indapamide. These results suggest that the reduction of blood pressure by the inhibition of angiotensin converting enzyme with captopril has the potential to ameliorate renal function of the SHR with remnant kidney, a model of chronic renal failure with hypertension, associated with the decreased concentration of plasma ANP. However, it remains to be determined whether the reduction of blood pressure by calcium channel blockers may be involved in the delayed progression of renal failure in this model since there were disparate effects on renal function and plasma ANP concentration with these two calcium channel blockers.

Animals↗

Intracellular compartmentalization of fura-2 dye demonstrated by laser-excitation fluorescence microscopy: a problem in measuring cytosolic free calcium concentration using fura-2 fluorescence in vascular smooth muscle cells.

Recently, we have developed a novel laser-excitation fluorescence microscope system to study intracellular calcium (Ca2+) in individual cultured vascular smooth muscle (VSM) cells using fluorescent indicators for (Ca2+). In the course of our study, it was shown that the subcellular fluorescence distribution of fura-2 was not homogeneous in VSM cells incubated with the acetoxy-methyl ester form of fura-2, fura-2/AM. The fluorescence appeared spotty or filamentous and resembled in shapes the intracellular organelles, suggesting that there was fura-2 dye compartmentalization in the organelles. To clarify the nature of the subcellular fluorescence, the soluble fraction of cells loaded with the dye was analyzed through high performance liquid chromatography (HPLC). We also examined the excitation spectra of fluorescence in the soluble fraction, which was compared with that in the cell suspension. Using HPLC, it has been shown that no other than fura-2 was found in the soluble fraction, whereas analyses of excitation spectra have indicated that the membrane fraction contained fura-2/AM or its lipophilic metabolite. On the other hand, indo-1 dye fluorescence showed a diffuse intracellular distribution, but the nuclear region had higher or sometimes lower fluorescence levels than the cytoplasm. The present results suggest that it may be necessary to assess subcellular fura-2 compartmentalization and possible interference by fura-2 AM or its lipophilic metabolite for the accurate measurement of intracellular Ca2+ concentration in VSM cells. It is also suggested that indo-1 may be more suitable for estimating Ca2+ concentration than fura-2 in individual VSM cells.

Animals↗

Subgingival administration of tetracycline on a collagen film.

The purpose of this study was to evaluate the duration of therapeutic effect after administration of the collagen film immobilized tetracycline (TC film). TC film or tetracycline non-immobilized placebo film was applied one time to the periodontal pocket (greater than or equal to 4 mm) of five periodontitis patients (20 teeth). The clinical and microbiological effects are summarized as follows: The group that received TC film continued to show significantly low values for bleeding upon probing the pocket depth for 3 and 4 weeks, respectively, after administration, but there was no significant difference in the plaque index or gingival index when compared with the group that received a placebo film. In the TC film group, the density of microorganisms and the proportion of motile rods and spirochetes were also significantly decreased 3 weeks after administration. These findings suggest that topically administered TC film remains both clinically and bacteriologically effective for 2 to 3 weeks.

Administration, Topical↗

[Application of local drug delivery system to periodontal therapy. 4. Comparison of the therapeutic effects of administration of a TC film or root debridement on human periodontal disease].

In 8 patients with periodontal diseases under good supragingival plaque control, 22 test teeth each having a pocket not more than 4 mm deep were treated respectively with 3 consecutive administrations of tetracycline immobilized cross-linked collagen film (TC film) at intervals of 1 week, with onceroot planing and with both of these. The therapeutic effects were compared both clinically and micro biologically. The results revealed improvements in clinical symptoms such as reduction in the depth of the pocket, bleeding on pocket probing and the like for each treatment group in 6-12 weeks. The second and third groups also showed remarked gingival recession. Further more, the density of intrapocket microorganisms showed a remarked decrease up to the 8th week for each treatment group and the population of spirochetes showed a decrease up to the 6th week for the first treatment group and up to the 8th-12th week for the second and third treatment group. The results show that both local application of the TC film and root planing are effective in periodontal treatment, but not the combined treatment.

Collagen↗

[Application of local drug delivery system to periodontal therapy. 5. Clinical and microbiological effects of TC film application in furcation involvements].

Two molars having furcation grade II involvements were selected from each of six patients with periodontal diseases. One molar received a local application of tetracycline immobilized cross-liked collagen film four times at one-week intervals (TC film-treated group) and the other received no treatment (non-treated group). The clinical and microbiological effects were, as follows, 1. Throughout the experimental period, no significant differences in pocket depth, attachment level, bleeding on pocket probing, periotron unit, gingival index and plaque index were noted between the TC film-treated group and the non-treated group. 2. One week after TC-film application, the treated group showed significant decreases in the density of microorganisms and the proportion of spirochetes compared with the non-treated group. The results revealed the insufficient effectiveness of the local application of TC film by itself for the treatment of teeth having furcation grade II involvements.

Collagen↗