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R Claus

Publications and source records attributed to R Claus.

At least 19 recordsLinked to original sources
PubMed2006

Influence of short-term confinement and exercise on tibia development in growing pigs.

The influence of short-term confinement and moderate exercise on tibia development was investigated in growing pigs (36-41 kg, 10 weeks at the beginning of the study). Animals were kept for 2 weeks either in individual crates of 0.8 m(2) ('confinement', n = 4) or kept in groups of four animals in large crates of 5.6 m(2) without ('control') or with additional exercise (30 min walking at 5 days/week; 'exercise'). Bone density and morphological parameters were evaluated by computer tomography (CT). Periosteal apposition and longitudinal growth were determined after polychrome sequential labelling in weekly intervals. Cortical areas of the cross sections at the mid-shaft and at 75% of the length of the bone measured distal to the carpus by CT were significantly correlated to each other (r = 0.70) and revealed a significant reduction in confined animals. This difference was explained by lower periosteal apposition rates in these animals compared with exercised and group-housed pigs. Similarly longitudinal growth and the formation and calcification of spongiosa of the tibiae were inhibited by confinement. Thus, 2 weeks of confinement led to significant differences in bone growth and metabolism in young growing piglets when compared with animals with moderate activity.

Animals↗
PubMed2005

Cellular localization of estrogen receptor-alpha (ERalpha) and -beta (ERbeta) mRNA in the boar testis.

Boar testes synthesize high amounts of estrogens which are known to stimulate several male sexual functions in a variety of extragonadal target tissues. Possible effects within the testis depend on the existence of the estrogen receptor subtypes alpha and beta (ERalpha, ERbeta). The precise cellular localization of these subtypes within the testis was, so far, based mainly on protein expression studies using different antibodies in several species including boars shows contradictory results. Therefore, we investigated the ERalpha and ERbeta gene expression using RT-PCR of testis homogenates and RT-PCR after UV-single cell microdissection combined with in-situ hybridization of four fertile boars with an average age of 32 weeks. Both ERalpha and ERbeta mRNA were found in testis homogenates. Using in-situ hybridization and UV-single cell microdissection ERalpha mRNA was present in type A and type B spermatogonia up to mid-pachytene primary spermatocytes in stage V-VIII and stage I of the seminiferous epithelial cycle, but not in other cells. ERbeta mRNA was found only in Sertoli cells. Interstitial Leydig cells revealed neither ERalpha nor ERbeta mRNA. The data suggest a direct impact of estrogen in the boar on Sertoli cell function via ERbeta and germ cell formation via ERalpha.

Animals↗
PubMed2005

Characterization of 11beta-hydroxysteroid dehydrogenase activity in testicular tissue of control and GnRH-immunized boars as a possible regulator of spermatogenesis.

Glucocorticoids are involved in the regulation of spermatogenesis in the boar testis by initiating apoptosis in early stages of germ cell development. Because cortisol activity is modulated by the 11beta-hydroxysteroid dehydrogenase system (11beta-HSD), the present study determined both 11beta-activating (reductive) and inactivating (oxidative) enzyme activities in testicular tissue preparations of control boars (n = 5), GnRH-immunized boars (n = 5), and immunized, estradiol-infused boars (n = 6) by radioenzyme assay based on the conversion of tritiated cortisol to cortisone in the presence of NAD+ (inactivation) or tritiated cortisone to cortisol in the presence of NADPH (activation). The presence of both isoforms, 11beta-HSD 1 and 11beta-HSD 2, was confirmed by RTPCR in testicular tissue of control boars. Additionally, cortisol, testosterone, estradiol, and LH were determined in blood plasma sampled twice before killing. Immunization led to a drop of LH from 4.3 +/- 0.3 pmol/L to 1.0 +/- 0.3 pmol/L (testosterone: 11.63 +/- 0.83 nmol/L vs. 0.28 +/- 0.07 nmol/L; 17beta-estradiol: 512.61 +/- 47.60 pmol/L vs. 77.05 +/- 14.00 pmol/L). Low 11beta-HSD reductive activity was found in boars (1 pmol steroid x min (-1) x mg (-1)). It decreased to trace amounts in immunized boars (0.07 pmol steroid x min (-1) x mg (-1)). Oxidative activity was found in boars with 10.19 +/- 2.28 pmol steroid x min (-1) x mg (-1) protein. Immunization led to a sharp decrease (0.08 +/- 0.03 pmol x min (-1) x mg (-1)). Infusion of 17beta-estradiol significantly elevated peripheral estradiol concentrations to 752.07 +/- 24.19 pmol/L which still is a physiological concentration in this species. The infusion led to a minimal reductive activity (0.04 pmol steroid x min (-1) x mg (-1)), but led to a 6-fold rise of the 11beta-HSD oxidative activity to 0.47 +/- 0.14 pmol x min (-1) x mg (-1) compared to immunized boars. It is concluded that the 11beta-HSD system is involved in the regulation of cortisol activity in the testis and thus in the regulation of spermatogenesis.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2005

Dose-dependent effects of resistant potato starch in the diet on intestinal skatole formation and adipose tissue accumulation in the pig.

Resistant starch (RS) intake leads to a reduction of apoptosis in the pig colon and thus to a reduction of skatole in the carcass. To determine the minimal amount of RS which is required for the effect, diets with varying amounts (20, 30 and 40%) of RS were fed to barrows and gilts. Controls were fed instead with 55% pre-gelatinized starch. Skatole was determined after slaughter in distal colon content and in adipose tissue (flare fat and belly fat). Resistant starch led to a dose-dependent reduction of skatole in the gut content from 134 microg/g dry matter (controls) to 4.8 microg/g in the 40% group. Flare fat concentrations were decreased from 159 to 20 ng/g fat and belly fat concentrations from 64 to 16 ng/g fat. Strategies to improve sensorial quality by feeding RS continuously or for only 1 week prior to slaughter are discussed.

Adipose Tissue↗
PubMed2004

Effects of dexamethasone application in growing pigs on hormones, N-retention and other metabolic parameters.

Many single effects of glucocorticoids are known but complex metabolic reactions in pigs in response to a glucocorticoid challenge were not reported. Seven pigs (mean weight 69 kg) with indwelling catheters were kept in metabolic crates. After a 7-day control period they were fed for 9 days with 0.4 mg dexamethasone (dex) per kg body weight daily, followed by another 9-day post-treatment period. Hormones and metabolic parameters were continuously determined in urine or blood plasma. Treatment significantly changed all parameters except non-esterified fatty acids. Cortisol decreased from 84.5 to 4.9 nmol/l, insulin-like growth factor I (IGF-I) from 17.5 to 10.8 nmol/l and aldosterone from 0.36 to 0.13 nmol/l. The N-retention decreased from 1.07 to 0.53 g/kg(0.75) and hydroxyproline from 2.97 to 1.05 mmol/day. An increase was found for urine volume (5.2 versus 13.6 l/day), urea-N (0.90 versus 1.43 g/kg(0.75)), allantoin (6.40 versus 8.75 mmol/day), glucose (3.9 versus 4.34 mmol/l) and insulin (6.21 versus 11.16 mU/l). In the post-treatment period IGF-I revealed a compensatory pattern (control period versus post-treatment period: 17.5 versus 22.9 nmol/l) whereas the other parameters were not significantly elevated. Data suggest that dex increased N-excretion both by inhibiting mitosis and resynthesis of proteins partly via a reduced collagen synthesis. Increased allantoin concentrations additionally pointed to increased apoptosis.

Animals↗
PubMed2004

Involvement of glucocorticoids in testicular involution after active immunization of boars against GnRH.

Active GnRH immunization of boars inhibits LH and testicular steroids but the consequences for spermatogenesis are unknown. Six boars were immunized three times against GnRH at 20, 24 and 28 weeks. Another six boars served as controls. Plasma LH and FSH were determined at 28 and 31 weeks. Testosterone and cortisol were determined before killing the pigs at 32 weeks. Tissue samples were taken for histology and fluid from the seminiferous tubuli for steroid determination. Individual germ cells were counted in histological sections. The glucocorticoid receptor (GCR), mitosis of spermatogonia and apoptosis were characterized by immunocytochemistry. Immunization reduced LH and testosterone to base levels whereas FSH was not changed. Testis weight was reduced by 64% due to a loss of Leydig cell cytoplasm (90.3%) and a decrease of tubule diameters (60.6%). Except for A-spermatogonia, all other spermatogenic cells were reduced by about 60%. Mitosis was reduced in immunized boars. Expression of GCRs was limited to spermatogonia and differed between immunized boars (8% of spermatogonia) and controls (2%). In the controls, androgen concentrations in tubular fluid were tenfold higher compared with immunized boars. Cortisol concentrations were of the order of 40 nmol/l both in the tubular fluid and blood plasma. These concentrations did not differ between groups. Apoptosis occurred only in spermatogonia and pachytene spermatocytes and was twofold higher in immunized boars compared with controls. Thus the availability of glucocorticoids in the tubuli and the expression of GCRs initiate apoptosis, which in turn reduces sperm yield. Testosterone is known to be an inhibitor of GCR expression, thus increasing the efficiency of spermatogenesis.

Animals↗
PubMed2003

Increased butyrate formation in the pig colon by feeding raw potato starch leads to a reduction of colonocyte apoptosis and a shift to the stem cell compartment.

Whereas butyrate is well known to induce apoptosis in transformed colon cells in vitro, evidence exists that it inhibits apoptosis of colon crypt cells in vivo. In this study, pigs were fed with resistant potato starch to increase microbial butyrate formation in the colon and to investigate its effects on mitosis and apoptosis. In addition, apoptosis regulating proteins were determined by immunocytochemistry, such as proapoptotic Bak, antiapoptotic Bcl-2, and the epidermal growth factor (EGF), which is synthesized by goblet cells and functions as a survival factor. Two groups of 6 barrows were both supplied with 381 g crude protein and 31 MJ metabolizable energy (ME) daily over a 19-day experimental period. The rations differed in the carbohydrate composition. The controls received gelatinized starch as the main carbohydrate, whereas the experimental group (butyrate group) received a ration with raw potato starch (low ileal digestibility). In the feces, butyrate concentration and pH were monitored daily. After killing the pigs, colon tissue was obtained for histologic and immunocytochemical evaluation, which was performed separately in the luminal, middle, and stem cell compartment of the crypts. In the butyrate group, the total number of apoptotic cells was reduced by 34% (P< or =.001) compared with controls, whereas the mitotic rate was not altered. The crypt depth was only moderately increased by 15%. Apoptosis in the luminal compartment of the butyrate group was reduced by 18.8%, but was increased by 21.7% in the stem cell compartment. The effect of butyrate on apoptosis was paralleled by an increased number of Bcl-2 positive cells mainly in the luminal compartment (butyrate: 2.6 cells; controls: 1.2 cells, P< or =.001), which was more pronounced compared with the number of Bak positive cells in the same compartment. Bak activity in the stem cell compartment was 3.4-fold increased compared with controls (P< or =.001). The size of EGF-positive stained mucus-droplets from the goblet cells was increased in the butyrate group (P< or =.001). We conclude that butyrate inhibits apoptosis of colonocytes in vivo. An excessive proliferation of crypts is counteracted by a shift of the remaining apoptosis towards the stem cell compartment.

Animals↗
PubMed2003

Influence of cortisol, gonadal steroids and an energy deficit on biochemical indicators of bone turnover in Swine.

In the pig a high growth potential seems to favour a disposition for skeletal problems. Hormones of growth hormone (GH)/insulin-like growth factor (IGF)-I axis as well as cortisol and gonadal steroids are endocrine determinants of the anabolic potential but their effects on bone turnover in pigs have not been described. Thus, key hormones were either infused for 7 days (cortisol, 5alpha-dihydrotestosterone (DHT), oestradiol) or influenced by Metyrapone (inhibition of cortisol synthesis) or energy deficit (increasing GH). Each treatment was carried out in six growing barrows/treatment. Bone turnover was characterized by daily measurements indirect parameter of osteoblastic and osteoclastic activity, osteocalcin (OC) and tartrate-resistant acid phosphatase (TRAP) respectively. All treatments except cortisol infusion seemed to favour bone formation, as they led either to a pronounced increase in OC (Metyrapone: +14%) or to significantly reduced TRAP (DHT: -9%, E2: -17%, energy deficit: -25%) followed by significantly higher OC (DHT: +9%, E2: +6%, energy deficit: +18%). Cortisol infusion affected bone loss mainly by a severe inhibition of osteoblastic activity (OC: -61%). Some reactions are explained by direct effects of the infused gonadal steroids on bone cells (inhibition of osteoclasts) or of the experimentally modified cortisol levels (inhibition of osteoblasts by cortisol). Other effects seem to be mediated by concomitant changes of IGF-I (inhibition of osteoclasts after energy deficit or cortisol) and GH-secretion (increased osteoblastic activity during energy deficit), respectively. Consequences for co-ordinated bone turnover are discussed.

Acid Phosphatase↗
PubMed2003

Porcine 11beta-hydroxysteroid dehydrogenase type 2 isoform: complete coding sequence and polymorphisms.

11Beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) is involved in the regulation of the peripheral glucocorticoid concentrations. Due to the central role of glucocorticoids in protein turnover, 11beta-HSD2 is a candidate gene for optimising production traits in livestock. In addition, mutant 11beta-HSD2 animals may be used as models for human disorders. Here, we present the complete porcine 11beta-HSD2 coding sequence, the RT-PCR strategy for the examination of the coding sequence and the polymorphisms found in the pig.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2003

Effects of butyrate on apoptosis in the pig colon and its consequences for skatole formation and tissue accumulation.

Evidence exists that butyrate inhibits apoptosis of colon crypt cells in vivo so that less tryptophan from cell debris is available for skatole formation by microbes in the pig colon. In this study, potato starch containing a high proportion of resistant starch was fed to test the hypothesis that increased butyrate formation will occur in the colon and contribute to reduced epithelial cell apoptosis, thus leading to reduced skatole formation and absorption. Two groups of six barrows were provided with catheters in the jugular vein and fed either a ration with pregelatinized starch (high ileal digestibility; controls) or potato starch (low ileal digestibility; PS) as the main carbohydrate. All pigs were fed 31 MJ of metabolizable energy and 381 g of crude protein per day. The controls were fed for 19 d. The PS group received the same control ration for 10 d, and then changed to the PS ration. The total feeding period of PS consisted of a 5 d adaptation period followed by another 19 d. In the continously sampled feces, pH, short chain fatty acids, and skatole were determined. Skatole was additionally measured in blood plasma that was sampled daily. After killing barrows at the end of the feeding period, fat tissue for skatole measurement and colon tissue for histological quantification of mitosis and apoptosis were obtained. Feeding potato starch led to a rapid 2.2 fold increase of fecal butyrate when compared both with the control period of the PS group and the control group (P < 0.001). PS feeding resulted in a decrease in pH from 7.3 to 5.3 (P < 0.001) and apoptosis from 2.06 cells/crypt to 0.90 cells (P < 0.01), whereas there was no change in mitosis. Consequently, skatole decreased both in feces (controls vs PS group: 120.0 vs 1.9 microg/g; P < 0.001) and in blood plasma (1.6 vs 0.2 ng/mL; P < 0.001). The mean concentration of skatole in fat tissue was 167 ng/g tissue in controls, and below the detection limit (0.8 ng/g) in the PS group (P < 0.001). It is concluded that butyrate-dependent inhibition of apoptosis in the colon due to potato starch feeding efficiently inhibits skatole production in barrows. Because of the depressed skatole levels, improved sensory quality of pork is possible.

Animal Feed↗
PubMed2002

Effects of malnutrition on the expression of daintain/AIF-1 in the gut mucosa of pigs.

The allograft inflammatory factor (AIF-1/daintain) is a hormone-like peptide produced by activated monocytic cells in a variety of traumatic, inflammatory and degenerative lesions. Gut-derived AIF-1 has been shown to modulate insulin production and to attenuate autoimmune diabetes. As the localization of this gastrointestinal peptide in the porcine duodenum is not known and the pig is a convenient model for the study of nutritional modulation of the mucosal immune compartment, we have localized expression of AIF-1 by immunohistology in the duodenum of either malnourished (energy and protein supply 50% of demands, n = 5) or optimally fed pigs (n = 5). AIF-1 macrophages were predominantly located at the villus tip. The number of positively stained cells per high-power field was significantly (P < or = 0.001) higher in the malnourished pigs (74.6 +/- 2.44; least square means +/- SEM) compared to optimally fed pigs (32.56 +/- 1.99). It is likely that the effect in malnourished pigs can be explained by a more pronounced antigen contact of macrophages due to loss of epithelial integrity. Thus, AIF-1 is a novel marker for the study of the nutritional regulation of the mucosal immune system of the pig. AIF-1 expression in the duodenum was further validated by polymerase chain reaction and sequencing. Surprisingly, we detected a slight deviation from the original sequence (probably representing an allelic variation) and an AIF-1 splice variant, previously not known to occur in pigs.

Amino Acid Sequence↗
PubMed2002

High-precision fluorescence assay for sphingomyelinase activity of isolated enzymes and cell lysates.

Sphingomyelinases are important enzymes of signal transduction. They catalyze the hydrolysis of sphingomyelin, giving rise to the intracellular formation of biologically active ceramide and phosphatidylcholine. Here we report on a fluorescence method for the fast and accurate determination of this enzyme in biological samples. The assay is based on a fluorescent sphingomyelin analog carrying fluorescent 7-nitro-2-1,3-benzooxadiazolyl amino-dodecanoic acid instead of an aliphatic acyl chain at the nitrogen atom. The fluorescent substrate is hydrolysed by sphingomyelinases to form fluorescent ceramide, which can be separated from the remaining substrate using TLC on silica gel. The fluorescence intensity pattern obtained on the TLC plate can accurately be determined using a CCD camera. Typically, a large number of samples can be analyzed simultaneously. Examples for the quantitative analysis of sphingomyelinases from freshly prepared cellular homogenates as well as from commercial sources are given.

4-Chloro-7-nitrobenzofurazan↗
PubMed2001

Comparison of blood markers for the longitudinal monitoring of osteoclastic activity in the pig.

In the present study the osteoclast activity was monitored longitudinally in porcine blood samples by measuring the tartrate-resistant acidic phosphatase (TRAP) activity with several methods described for human samples. These methods differed in their specificity for bone-specific TRAP and in their practicability. The validity of TRAP measurements was evaluated by comparison with the peripheral concentrations of the N-terminal fragments of type I collagen with attached cross-links (NTx), a highly bone-specific parameter of bone collagen degradation, using a commercially available test kit developed for human samples. On selected days urine samples were collected for the determination of pyridinium cross-links. The determinations of cross-links in urine were normalized for the creatinine concentrations. However, they were not related to fluoride-sensitive TRAP (fsTRAP) and NTx measurements in serum. The fsTRAP activity in serum, which is assumed to be highly bone-specific, was highly correlated with the NTx concentrations in serum under different experimental conditions. As measurements in blood may be more easily standardized than those in urine, fsTRAP measurements in serum seem to be a highly practicable method to characterize osteoclastic activity in the pig.

Acid Phosphatase↗
PubMed2001

Activities of 11beta-hydroxysteroid dehydrogenase 2 in different regions of the intestinal tract of pigs.

11beta-Hydroxysteroid dehydrogenase 2 (11beta-HSD 2) converts active cortisol to inactive cortisone and thus modifies the availability of glucocorticoids for the target tissue. An additional function is the protection of the aldosterone receptor in mineralocorticoid-sensitive tissues such as the kidney and the gut. The occurrence of 11beta-HSD 2 activity was investigated in several species. Data for the pig, however, so far are missing. The activity was determined by a radio-enzyme-assay based on the conversion of tritiated cortisol to cortisone under standardized incubation conditions in supernatants of homogenates prepared from tissues of four castrates. Tissues comprised several locations along the intestinal tract and in addition kidney, lung, muscle, heart, spleen and pancreas. Highest values of the enzyme activity were found in kidney and very low activities in lung tissue but no activity in muscle, spleen, heart and pancreas. In the gut, there was a continuous increase in enzyme activity from the duodenum (0.60 pmol x min(- 1) x mg protein(- 1)) towards the colon with maximum values in the colon transversum (23.32 pmol x min(- 1) x mg protein(- 1)). In the colon the activity was 10-fold higher than in jejunum and 3-fold higher compared to ileum. The activities did not differ significantly between the colon transversum and colon descendens.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2001

Low-dose levalbuterol in children with asthma: safety and efficacy in comparison with placebo and racemic albuterol.

BACKGROUND: Racemic albuterol (RAC) is an equal mixture of (R)-albuterol and (S)-albuterol. Only the (R)-isomer, levalbuterol (LEV), is therapeutically active. Lower doses of LEV, devoid of (S)-albuterol, have demonstrated efficacy comparable to that of higher doses of the (R)-isomer administered as a component of RAC. OBJECTIVE: The purpose of this study was to determine whether LEV results in improved safety and efficacy in children. METHODS: Asthmatic children aged 4 to 11 years (n = 338; FEV(1), 40% to 85% of predicted) participated in this multicenter, randomized, double-blinded study and received 21 days of 3-times-a-day treatment with nebulized LEV (0.31 or 0.63 mg), RAC (1.25 or 2.5 mg), or placebo. The primary endpoint was FEV(1) (peak percent change). Adverse events, clinical laboratory test results, vital signs, and electrocardiograms were evaluated for safety. RESULTS: All active treatments significantly improved the primary endpoint in comparison with placebo (P < .001). Significant differences in FEV(1) were noted immediately after nebulization (median change, 2.0%, 19.0%, 18.1%, 12.4%, and 15.6% for placebo, LEV 0.31 and 0.63, RAC 1.25 and 2.5 mg, respectively; P < .05 vs placebo; P < .05 for LEV 0.31 and 0.63 vs RAC 1.25 mg). LEV 0.31 mg was the only treatment not different from placebo for changes in ventricular heart rate, QT(c) interval, and glucose (P > .05). All active treatments decreased serum potassium (range, -0.3 to -0.6; P < .002 vs placebo), and RAC 2.5 mg caused the greatest change (P < .005 vs other actives). In a patient subset with severe asthma, a dose-response relationship was observed for levalbuterol, indicating that higher doses were more effective. CONCLUSION: LEV was clinically comparable to 4- to 8-fold higher doses of RAC, and it demonstrated a more favorable safety profile. LEV 0.31 mg should be used as the starting dose in 4-11 year old children with mild to moderate persistent asthma. Patients with severe disease might benefit from higher doses.

Adrenergic beta-Agonists↗
PubMed2001

Butyric acid stimulates rumen mucosa development in the calf mainly by a reduction of apoptosis.

In ruminants the stimulation of papillar growth by butyric acid is well described but effects on mitosis and apoptosis are not known. To clarify the effect of short chain fatty acids three groups of three calves received a basic ration of 100 g hay per day for 6 weeks and additionally milk replacer. From these, two groups were fed with increasing amounts of the salts of either propionic acid (53 to 390 g) or butyric acid up to (54 to 326 g). The control group instead received an additional isocaloric amount of milk replacer. Mitosis was characterized by Ki67 immunoreactivity, apoptosis by a modified TUNEL assay and by electron microscopy. The feeding regimes led to significant differences of papillar length, increasing from 1.0 mm (controls) to 2.2 mm (propionic acid) and 4 mm (butyric acid). This enlargement was partly explained by an increased mitotic rate for the two fatty acid groups. The difference between the fatty acid groups was mainly explained by different apoptotic rates which were only one third for butyric acid compared to propionic acid (P < 0.001). In conclusion, butyric acid is a specific inhibitor of ruminal apoptosis in vivo.

Animal Feed↗
PubMed2001

Ceramide induces aSMase expression: implications for oxLDL-induced apoptosis.

Sphingomyelinase (SMase) stimulation and subsequent ceramide generation are suggested to be involved in signal transduction of stress-induced apoptosis. We now show that apoptosis of human macrophages (MPhi) and fibroblasts initiated by oxidized low density lipoproteins (minimally modified LDL, mmLDL) is associated with an increase in acid SMase (aSMase, E.C. 3.1.4.12) expression and ceramide concentration. Application of a novel, potent, and specific inhibitor of aSMase expression (NB6) diminished the effects of mmLDL and C6-ceramide treatment by inhibiting transcription via Sp1 and AP-2. Moreover, apoptosis was abolished after mmLDL and C6-ceramide treatment of hereditary aSMase-deficient fibroblasts (from Niemann-Pick patients). We suggest that in mmLDL-initiated apoptosis 1) enhanced ceramide generation via aSMase appears to be required as well as 2) a positive feedback control of aSMase expression by the increase in intracellular ceramide concentration.

Apoptosis↗