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Comparison of the antisecretory effect of endogenous forms of peptide YY on fed and fasted rat jejunum.

It is intriguing that the antisecretory peptide YY is present in plasma in two forms: PYY1-36 and PYY3-36. PYY3-36 has been found in human and rabbit blood within 30 min of the beginning of the meal, when the peak of water and electrolyte secretion occurs in the duodeno-jejunum. The aim of this study was therefore to compare the antisecretory effect of PYY1-36 and PYY3-36 in fed and fasted rat jejunum. The variations in electrolyte secretion were assessed by measuring the variations in short-circuit current (delta Isc) and transepithelial isotopic chloride fluxes in jejunal mucosa isolated from fed and fasted animal, and mounted in Ussing Chambers. In fasted animals, 2 x 10(-7) M PYY3-36 induced a reduction in Isc of -0.50 +/- 0.01 microEq/hr.cm2, which was not statistically different from that induced by 2 x 10(-7) M PYY1-36 (-0.60 +/- 0.01 microEq/h cm2). In contrast, in fed animals, 2 x 10(-7) M PYY3-36 did not trigger a significant response on Isc and net chloride flux, while the response to PYY1-36 was present but blunted. The absence of response was probably not related to the presence of secretory peptides because PYY3-36 was still able to induce a reduction in Isc after stimulation by a series of 10 different secretory peptides. After 10(-8) M PYY3-36 addition to an epithelium from the fasted animal, response to 10(-7) M PYY3-36 was blunted for 30 min and returned to control value after 60 min. Plasma concentration of PYY was higher in the fed rats compared to fasted (213.78 +/- 38 vs. 53.62 +/- 11.47 pg/ml p < 0.01). After incubation of crypt cells with or without 0.1 microM of unlabeled PYY for 60 min, Scatchard analysis of equilibrium binding data show that binding capacity (Bmax) of receptors was reduced when crypt cells were previously incubated with unlabeled PYY without significant modification of dissociation constants. Bmax were 183 +/- 27 in control vs. 56 +/- 11 fmol/mg protein. These results confirm the antisecretory activity of PYY1-36 in the jejunum of fasted and fed rats. They further indicate that PYY3-36 displays similar activity to PYY1-36 in fasted animals, but lack of activity in fed animals. These results suggest that the two circulating forms of PYY act as antisecretory peptides by two different mechanisms, implying a C-terminal specificity.

Animals↗

Inhibition of collagen biosynthesis and increases in low molecular weight IGF-I binding proteins in the skin of fasted rats.

Insulin-like growth factor-I (IGF-I) is an important stimulator of collagen biosynthesis and prolidase activity in connective tissue cells. The disturbances in skin collagen metabolism (reflected by significant decrease in skin collagen content, collagen biosynthesis and prolidase activity) in fasted rats were accompanied by decrease in serum IGF-I level. Fasted rat serum was found to contain about 58% of IGF-I (101.6 +/- 15.4 ng/ml) as compared to control rat serum (175.7 +/- 19.8 ng/ml), while the skin of control and fasted rats contained similar concentrations of IGF-I (about 77 ng/g tissue). The insulin-like growth factor binding proteins (IGFBPs) of sera and tissue extracts (known to regulate IGF-I activity) were analysed by ligand blotting. In the serum of control rats one IGFBP band of about 46 kDa (corresponding to the acid-dissociated IGFBP-3) was detected. In the serum of fasted rats the 46 kDa IGFBP was not observed, however, an other IGFBP of about 30 kDa (corresponding to low molecular weight IGFBPs, e.g. IGFBP-1 or IGFBP-2) was found. The intensity of IGF-I binding to the 30 kDa IGFBP was much higher than that of IGFBP-3, found in control rat serum. Control and fasted rat skin contained similar IGFBPs, however their IGF-I binding abilities were much lower, compared to their serum counterparts. It was found that 46 kDa and 30 kDa proteins, observed in ligand blotting represent IGFBP-3 and IGFBP-1 or IGFBP-2. respectively as demonstrated by western immunoblot analysis. An increase in IGF-binding to 30 kDa IGFBP-1 and/or IGFBP-2 (known as an inhibitors of IGF-dependent functions) in the skin of fasted rats may explain the mechanism of reduced collagen biosynthesis and deposition in tissues during fasting.

Animals↗

Changes in serum concentrations and pituitary content of the two prolactins and growth hormone during the reproductive cycle in female tilapia, Oreochromis mossambicus, compared with changes during fasting.

Patterns of change in serum concentrations and pituitary content of GH and two tilapia prolactins (PRL177 and PRL188) were examined during the reproductive cycle of female tilapia, Oreochromis mossambicus, adapted to fresh water and to seawater. Changes in these hormones during fasting were examined to elucidate whether changes observed during brooding could be attributed to a reduction in feeding during brooding. Serum concentrations of GH increased prior to pituitary content during the brooding phase of the reproductive cycle. In contrast, pituitary content of GH increased prior to serum concentrations during fasting. There was no consistent pattern of change in serum or pituitary PRL levels during the reproductive cycle, among experiments. Serum concentrations of PRL177 were elevated in all fasted fish, whereas PRL188 was elevated during fasting in males but not females. The increases in the serum concentration of PRLs and GH, and in the pituitary content of GH in response to fasting support the notion that these hormones are involved in the regulation of the use of metabolic substrates in tilapia. We conclude that reduced food intake during brooding may contribute to changes in serum and pituitary levels of the PRLs and GH observed during the reproductive cycle. Nevertheless, differences between changes in serum and pituitary GH during brooding and fasting suggest GH has actions in reproduction, and changes in GH during brooding are not only in response to fasting.

Analysis of Variance↗

Effect of green tea in the prevention and reversal of fasting-induced intestinal mucosal damage.

OBJECTIVE: Epidemiologic studies have suggested that high consumption of green tea protects against the development of chronic active gastritis and decreases the risk of stomach cancer. The effect of green tea on the intestinal mucosa was not studied previously, so we examined the effects of green tea on the intestinal mucosa of fasting rats in a controlled experimental setting. METHODS: Two sets of experiments were performed. In the recovery set, rats were fasted for 3 d, after which they were allowed free access to water, black tea, green tea, or vitamin E for 7 d. On day 8, the animals were killed, and small bowels were removed for histologic examination. In the pretreatment set, rats were allowed a normal diet, but the water supply was replaced with green tea, black tea, or vitamin E for 14 d. They were subsequently fasted for 3 d. On day 4, the rats were killed, and small bowels were removed for histologic examination. RESULTS: In the recovery set, fasting for 3 d caused shortening of villi, atrophy, and fragmentation of mucosal villous architecture, with a significant (P < 0.0001) reduction in the length and surface area of the villi. Ingestion of green tea and, to a lesser extent, vitamin E for 7 d helped in the recovery of villi to normal. In the pretreatment set, drinking green tea, black tea, or vitamin E for 14 d before fasting protected intestinal mucosa from damage. CONCLUSION: The mucosal and villous atrophy induced by fasting was reverted to normal by the ingestion of green tea and, to a lesser extent, vitamin E. Black tea ingestion had no effect. In addition, ingestion of black tea, green tea, and vitamin E before fasting protected the intestinal mucosa against atrophy.

Animals↗

Renal function in suckling and fasting pups of the northern elephant seal.

Elephant seals fast for prolonged periods without access to water. This is made possible, in part, by reductions in urine production. However, the mechanisms involved in reducing urine production are not understood. In this study, glomerular filtration rate (GFR) was measured in five northern elephant seal pups (Mirounga angustirostris) via the inulin clearance technique. Measurements were made during day 9 and day 18-22 of nursing and the second and eighth week of the postweaning fast. Plasma aldosterone and cortisol concentrations, quantified by radioimmunoassay, were measured in eight other weanlings during the second and eighth week of the fast. Mean GFR was 79.3+/-29.3 ml/min during the early suckling period and 78.2+/-17.1, 89.8+/-52.7, and 80.4+/-12.2 ml/min during the late suckling, early fasting and late fasting periods, respectively. Differences between nursing and fasting were insignificant, possibly because reduced protein oxidation during suckling and rapid recruitment of protein for tissue synthesis obviated the need for postprandial hyperfiltration. Alternatively, maintenance of GFR during fasting may facilitate urea concentration by compensating for reductions in the fractional excretion of urea. It is further hypothesized that aldosterone is primarily responsible for mediating renal water reabsorption in this system.

Aldosterone↗

Serum and antral gastrin levels in fed and fasted rats: relation to aging.

The effect of short fasting for up to 24 h on serum and antral gastrin concentrations and G cell ultrastructure has been examined in the young rat compared with the middle-aged rat. The serum gastrin levels at 24-h fasting were markedly reduced in both young and middle-aged rats. There was also a significant decrease in antral gastrin concentrations after 24 h of fasting in the middle-aged rats. By contrast, the antral gastrin concentrations in the young rats increased progressively and significantly with fasting for up to 24 h. These responses were associated with a significant increase in the content of secretory granules of G cell, which was at its greatest by 24 h. The antral gastrin level in the 48-h fasting rats was markedly reduced to a level below that for the prestarvation group. By 48 h of starvation, the amount of secretory granules in G cell was significantly reduced (P < 0.05) compared with the 24-h fasting group. These results indicate that the effects of fasting on the antral gastrin levels in young rats differ from those of the middle-aged and that starvation for up to 24 h caused a significant increase in the antral gastrin content in the young rats' stomach.

Aging↗

Glycosaminoglycan-degrading enzymes in the skin of fasted rats.

During fasting of animals, there is decreased content of skin glycosaminoglycans (GAGs) accompanied by decrease in their biosynthesis. Since tissue GAG content depends on both synthesis and degradation of these molecules, we asked whether fasting affects the activity of several tissue glycosidases. Therefore we measured the activity of skin neutral and acidic endoglycosidases, some exoglycosidases: beta-N-acetylhexosaminidase [EC 3.2.1.30], beta-galactosidase [EC 2.1.23], beta-glucuronidase [EC 3.2.1.31], alpha-iduronidase [EC 3.2.1.76], and two sulfatases: arylsulfatase B [EC 3.1.6.1] and 6-sulfatase [EC 3.1.6.14] in the skin of control and fasted rats. Although fasting was accompanied by distinct decrease in the activity of most neutral endoglycosidases, no characteristic changes in the activity of exoglycosidases were found. In contrast, we found that fasting is associated with increase in the activity of acidic endoglycosidases (of lysosomal origin) which degraded hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate and heparin. The same GAGs were decreased in the skin of fasted rats. Our data suggest that the phenomenon is a result of increased intracellular degradation of these molecules. Therefore, not only decreased biosynthesis of GAGs during fasting, but also increased their intracellular degradation may contribute to decrease in GAG skin content.

Animals↗

Effects of fasting during mid pregnancy or early lactation on mammary development and milk yield in mice.

Mice were fasted during pregnancy or early lactation and the effects on mammary development and milk yield studied on d 13 and d 18 of pregnancy and on d 7 of lactation. Fasting during pregnancy reduced body weight and mammary weight on d 13 of pregnancy but not on d 18. Mammary concentrations and total contents of DNA and RNA ([DNA], [RNA], DNAt, RNAt) were increased or unchanged on d 13 but significantly decreased on d 18. Fasting had no effect on fetal number or weight at either stage of pregnancy. Fasting on d 1 of lactation reduced mammary weight, DNAt and RNAt (but not [DNA] or [RNA]) and the incorporation of tritiated thymidine into DNA or d 2 of lactation. Mammary gland weight and composition on d 7 of lactation were not significantly affected by fasting for 24 h on d 1 of lactation or for 40 h on d 11-13 of pregnancy, except that DNAt was decreased slightly by the latter treatment. Milk yield (litter weight gain) was depressed markedly during fasting on d 1 of lactation, but thereafter recovered so that it was the same as controls between d 3 and 13 of lactation; after d 13 it fell once more. A 40 h fast on d 11-13 of pregnancy had no effect on milk yield. Thus, although normal mammary development was inhibited by starvation, the gland was subsequently able to compensate so that milk yield was not reduced.

Animals↗

Enhanced plasma availability of the metabolites of albendazole in fasted adult sheep.

The influence of fasting prior to treatment and of dosing rate on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites was studied in adult sheep grazing on pasture. A micronized suspension of ABZ was administered orally at either 7.5 mg/kg (group A) or 11.3 mg/kg (group C) to sheep fed ad libitum, and at 7.5 mg/kg to sheep subjected to a 24 h fasting period prior to treatment (group B). Blood samples were taken serially over 96 h after treatment, and the plasma was analysed for ABZ and its metabolites by high-performance liquid chromatography. ABZSO and ABZSO2 were recovered from the plasma. Fasting induced marked modifications in the pharmacokinetic behaviour of the ABZ metabolites in sheep. An extended absorption process, with a delayed peak concentration in the plasma, was observed for both metabolites in the fasted sheep. Significantly higher area under the curve (AUC) and peak plasma concentration (Cmax) values were obtained for both metabolites in the fasted animals compared to those fed ad libitum. Delayed elimination with prolonged detection in plasma was also observed in the fasted sheep. Treatment with ABZ at 7.5 mg/kg in the starved animals resulted in bioequivalence to the administration of the compound at a 50% higher dose rate (11.3 mg/kg) in the fed animals. It is suggested that fasting enhances ABZ dissolution and absorption by delaying its passage down the digestive tract.

Albendazole↗

The influence of religious fasting on basal tear secretion and tear break-up time.

Muslims abstain from food and drink from dawn to sunset during the holy month of Ramadan. An extended strict fasting may influence tear secretion and quality. We investigated changes in basal tear secretion (BTS) and tear break-up time (BUT) at the beginning and at the end of fasting on 32 healthy male patients with a mean age of 22.3 +/- 2.9 years. Body weight and urine specific gravity were also determined to assess the extent of dehydration due to fasting. Each case lost 0.1-1.25 kg of body weight while urine specific gravity changes were statistically insignificant. Mean BTS amount was 19.9 +/- 10.9 mm at the initial examination and 19.7 +/- 11.5 mm at the end of fasting (p = 0.9). BUT values were 20.1 +/- 9.3 sec at the beginning of fasting and 23.5 +/- 14.9 sec at the end of fasting (p = 0.19). We found that religious fasting in the winter season does not seem to affect BTS and BUT values in healthy individuals.

Adult↗

The cholesterol-lowering property of soybeans fed to rats is related to the fasting duration.

Numerous factors affect plasma cholesterol and, therefore, represent potential interferences with the specific effects of diet on lipid metabolism. After casein intake, serum cholesterol levels depend on many experimental conditions in rats, such as the type of casein, the presence or absence of cholesterol in the diet, the age and strain of rat, the diet composition, the nutritional status. The effect of fasting duration on selected parameters was studied in adult male Wistar rats fed a 20% casein and 1% cholesterol-based diet. No changes were observed in total serum, lipoproteins-B and HDL cholesterol and in triglyceride values after an 8 h-fast compared to non-fasted animals. A significant decrease was induced in total and lipoproteins-B cholesterol with a 12 h-fast. A prolonged fast resulted in a significant decrease in these parameters and in triglycerides and in HDL-cholesterol levels. Fasted animals fed heated soybean meal instead of casein did not display a marked decrease in serum lipids. It appeared that the fasting effect was more marked in animals fed casein than in animals fed soybeans. These results showed the importance of experimental conditions such as nutritional status of animals when blood samples are taken in studies of the hypocholesterolemic effect of soy protein compared to casein.

Animals↗

Characterization of the myosin heavy chains of avian adult fast muscles at the protein and mRNA levels.

High resolution anion-exchange chromatography of myosin subfragment-1 in avian fast muscles revealed five fast heavy chains (I-V) expressed in muscle-specific patterns. Sequence analysis of a unique peptide established that the proteins differed in primary structure and suggested correlation with heavy chain genes identified independently by Robbins and coworkers. The identities of the isoforms and their expression patterns were confirmed at the mRNA level by a reverse-transcription, 5'-anchored PCR procedure. The fast white pectoralis major muscle possessed heavy chain I, the posterior latissimus dorsi muscle, of similar fibre type, expressed heavy chains I, III and IV. The fast red adductor superficialis muscle expressed either, or both, of heavy chains II and IV. The lateral gastocnemius muscle, of mixed fibre type, expressed heavy chains II-V. In general, heavy chains I, III and V appeared to be favoured in fast white fibres, while heavy chains II and IV were characteristic of fast red fibres. These results imply a greater subtlety of fast muscle function than has previously been appreciated.

Amino Acid Sequence↗

The metabolic response of tumour-bearing mice to fasting.

The suggestion that the ketonaemic response to fasting may be altered in the tumour-bearing state was investigated by studying the metabolism of fasted C57/BL6j mice bearing transplanted B16 melanomas. Ketone body (D-3-hydroxybutyrate and acetoacetate) concentrations in the blood of the tumour-bearing mice were significantly increased after a 24 h fast compared to control mice with identical dietary histories. Hepatic glycogen levels were lower at the start of the fasting period in the tumour-bearing mice as were the fat stores. The loss of adipose tissue during the fasting period was greater in the tumour-bearing mice. After 48 h of fasting, the ketonaemia was significantly lower in the tumour-bearing mice compared to the appropriate controls. Two distinct metabolic states are indicated in these fasted tumour-bearing mice, one characterised by accelerated ketonaemia, and a later, near terminal stage, where fat deposits are markedly depleted and ketonaemia is decreased.

3-Hydroxybutyric Acid↗

Muscle degradation in uremia: 3-methylhistidine release in fed and fasted rats.

The rate of myofibrillar protein degradation was measured by 3-methylhistidine (3MH) release in moderately uremic and sham-operated control rats. The rats were studied in the fed state or after 24 and 48 hours of fasting. When fed, both uremic and control rats gained weight at the same rate. During 48 hours of fasting, the uremic animals lost more weight (17.1%) than the shams (13.2%). The ratio of gastrocnemius muscle protein per gram of wet weight was not significantly different under any conditions. When fed and 48-hour fasted animals are compared, urinary excretion of 3MH rose from 0.81 to 1.32 moles per 24 hr per 100 g of initial body wt shams and from 0.90 to 1.30 moles per 24 hr per 100 g of initial body wt in the uremics. When ratio of 3MH to creatinine excretion in the urine was compared, there was no change in 3MH excretion between 0 and 24 hours, but there was an increase between 24 and 48 hours. Analysis of serum and muscle samples from fed and 48-hours fasted animals revealed that the concentrations of 3MH increased in both groups during fasting, with the uremic rats having a large increase in the total body 3MH pool. Myofibrillar degradation rates calculated from the sum of urinary excretion plus the changes in body 3MH pool size revealed that with moderate fasting, degradation rates increased in both sham and uremic rats with a larger increase being seen in the uremic group. After 48 hours of fasting, the increased amount of 3MH released from muscle of uremic rats was comparable to their larger percentage weight loss.

Animals↗

Obesity, fasting plasma insulin, and C-reactive protein levels in healthy children.

OBJECTIVE: Obesity is associated with hyperinsulinemia and increased level of C-reactive protein in older children and adults, but little is known about these relationships in very young children. We examined these relationships in healthy 2- to 3-year-old children. RESEARCH METHODS AND PROCEDURES: Analyses were performed on data from 491 healthy 2- to 3-year-old Hispanic children enrolled in a dietary study conducted in New York City, 1992 to 1995. RESULTS: Body mass index (BMI), ponderal index, and sum of four skinfolds were highly correlated (r > 0.75) in both boys and girls. Fasting insulin and glucose levels were only modestly correlated (r = 0.37 for boys and r = 0.28 for girls; p < 0.001 for both), but essentially all of the variability in a calculated index of insulin resistance was attributable to variability in fasting insulin level. The correlations of BMI with fasting insulin level were r = 0.16 (p < 0.05) in boys and r = 0.14 (p < 0.05) in girls. In separate multivariate regression analyses adjusting for age and sex, BMI and ponderal index were associated with fasting plasma insulin level (p < 0.001 for both obesity measures). In multivariate regression analyses adjusting simultaneously for age, sex, and either BMI or ponderal index, fasting insulin level, but not these obesity measures, was associated with C-reactive protein level. DISCUSSION: Obesity is associated with higher fasting insulin level, and fasting insulin is associated with C-reactive protein level, in healthy 2- to 3-year-old children.

Blood Glucose↗

Effects on health of fluid restriction during fasting in Ramadan.

During the 9th month (Ramadan) of the Islamic calendar (Hijra) many millions of adult Muslims all over the world fast during the daylight hours. Since Hijra is a lunar calendar, Ramadan occurs at different times in the seasonal year over a 33-year cycle. Fasting during Ramadan is partial because the abstention from food, fluid, tobacco and caffeine is from sunrise to sunset. Several categories of people are exempt or can postpone the Ramadan fast. The effect on health and well being of the month-long intermittent fast and fluid restriction has been studied in various potentially vulnerable groups in addition to normal healthy individuals in many countries. The majority of the studies have found significant metabolic changes, but few health problems arising from the fast. A reduction in drug compliance was an inherent negative aspect of the fast. Common findings of the studies reviewed were increased irritability and incidences of headaches with sleep deprivation and lassitude prevalent. A small body mass loss is a frequent, but not universal, outcome of Ramadan. During the daylight hours of Ramadan fasting, practising Muslims are undoubtedly dehydrating, but it is not clear whether they are chronically hypohydrated during the month of Ramadan. No detrimental effects on health have as yet been directly attributed to negative water balance at the levels that may be produced during Ramadan.

Dehydration↗

Stimulation by leptin of 3H GDP binding to brown adipose tissue of fasted but not fed rats.

OBJECTIVES: To assess the effects of intracerebroventricular (i.c.v.) leptin administration on rats fed ad libitum or fasted on 3H GDP binding to brown adipose tissue (BAT). SUBJECTS: Groups of 5-6 ten-week-old male Wistar rats. EXPERIMENTAL DESIGN: An i.c.v. cannula was inserted and unilateral denervation of interscapular brown adipose tissue (BAT) was performed 5 d before each study. Thereafter, leptin was infused i.c.v. during 72 h while rats were fed ad libitum or fasted. Vehicle-infused, pair-fed or fasted rats were used as controls. MEASUREMENTS: 3H GDP binding to innervated and denervated BAT mitochondria. RESULTS: 3H GDP binding to innervated or denervated BAT of rats fed ab libitum compared to vehicle-infused, pair-fed rats was not increased by i.c.v. leptin. 3H GDP binding was lower in fasted than in fed rats, and the difference was larger in innervated than denervated BAT. I.c.v. leptin increased 3H GDP binding by 30% in innervated, and by 51% in denervated BAT (P < 0.05) in fasted rats. CONCLUSIONS: I.c.v. leptin does not increase 3H GDP binding to BAT of rats fed ad libitum compared to pair-fed (food-restricted) rats. In contrast, i.c.v. leptin produces a mild stimulation of 3H GDP binding to BAT of fasted rats. This effect is not mediated by the sympathetic nervous system, because it is observed in both innervated and denervated BAT. These results are compatible with the concept that, in fasting rats, the decrease in leptin secretion contributes to the reduction in 3H GDP binding to BAT mitochondria.

Adipose Tissue, Brown↗

Insulin determines leptin responses during a glucose challenge in fed and fasted rats.

OBJECTIVE: Leptin secretion has been shown to respond acutely to changes in blood glucose and insulin. Nutritional state also has a marked effect on both the level of circulating leptin protein and leptin gene expression. The aim of this study was to assess whether the prior nutritional state altered the leptin secretory response to an acute glucose challenge, and to determine potential mechanisms. DESIGN: Male fed or fasted rats (200-250 g) were administered a single intravenous glucose bolus (1, 4 or 7 g/kg). The serum leptin, glucose, insulin and free fatty acid responses were studied over the following 5 h. The level of leptin gene expression and leptin protein was then determined in the epididymal fat pads, and in fed and fasted untreated rats for basal comparison. RESULTS: Leptin secretion in response to glucose was suppressed in fasted rats following all glucose doses. The total leptin response was correlated with the total insulin response in all conditions (r = 0.85) and with the glucose response in fed rats (r = 0.69). Both leptin gene expression and leptin protein content were lower in basal fasted rats. Leptin gene expression and leptin protein content still remained lower 5 h following a glucose bolus but there was partial reversal of the effects of fasting following the 7 g/kg glucose dose. CONCLUSIONS: Leptin secretion in response to an intravenous glucose bolus was determined by the insulin response and was significantly suppressed in fasted compared to fed rats. In addition to differences in the total insulin response of the animals, lower leptin responses may be facilitated by lower levels of both leptin gene mRNA and pre-existing leptin protein in epididymal adipose tissue of fasted rats.

Adipose Tissue↗